Saturday, August 31, 2019

The Twilight Saga 2: New Moon Chapter 14 FAMILY

I COWERED INTO JACOB'S SIDE, MY EYES SCANNING the forest for the other werewolves. When they appeared, striding out from between the trees, they weren't what I was expecting. I'd gotten the image of the wolves stuck in my head. These were just four really big half-naked boys. Again, they reminded me of brothers, quadruplets. Something about the way they moved almost in synchronization to stand across the road from us, the way they all had the same long, round muscles under the same red-brown skin, the same cropped black hair, and the way their expressions altered at exactly the same moment. They started out curious and cautious. When they saw me there, half-hidden beside Jacob, they all became furious in the same second. Sam was still the biggest, though Jacob was getting close to catching up with him. Sam didn't really count as a boy. His face was oldernot in the sense of lines or signs of aging, but in the matunry, the patience of his expression. â€Å"What have you done, Jacob?† he demanded. One of the others, one I didn't recognizeJared or Paulthrust past Sam and spoke before Jacob could defend himself. â€Å"Why can't you just follow the rules, Jacob?† he yelled, throwing his arms in the air. â€Å"What the hell are you thinking? Is she more important than everythingthan the whole tribe? Than the people getting killed?† â€Å"She can help,† Jacob said quietly. â€Å"Help!† the angry boy shouted. His arms begin to quiver. â€Å"Oh, that's likely! I'm sure the leech-lover is just dying to help us out!† â€Å"Don't talk about her like that!† Jacob shouted back, stung by the boy's criticism. A shudder rippled through the other boy, along his shoulders and down his spine. â€Å"Paul! Relax!† Sam commanded. Paul shook his head back and forth, not in defiance, but as though he were trying to concentrate. â€Å"Jeez, Paul,† one of the other boysprobably Jaredmuttered. â€Å"Get a grip.† Paul twisted his head toward Jared, his lips curling back in irritation. Then he shifted his glare in my direction. Jacob took a step to put himself in front of me. That did it. â€Å"Right, protect her!† Paul roared in outrage. Another shudder, a convulsion, heaved through his body. He threw his head back, a real growl tearing from between his teeth. â€Å"Paul!† Sam and Jacob shouted together. Paul seemed to fall forward, vibrating violently. Halfway to the ground, there was a loud ripping noise, and the boy exploded. Dark silver fur blew out from the boy, coalescing into a shape more than five-times his sizea massive, crouched shape, ready to spring. The wolf's muzzle wrinkled back over his teeth, and another growl rolled through his colossal chest. His dark, enraged eyes focused on me. In the same second, Jacob was running across the road straight for the monster. â€Å"Jacob!† I screamed. Mid-stride, a long tremor shivered down Jacob's spine. He leaped forward, diving headfirst into the empty air. With another sharp tearing sound, Jacob exploded, too. He burst out of his skinshreds of black and white cloth blasted up into the air. It happened so quickly that if I'd blinked, I'd have missed the entire transformation. One second it was Jacob diving into the air, and then it was the gigantic, russet brown wolfso enormous that I couldn't make sense of its mass somehow fitting inside Jacobcharging the crouched silver beast. Jacob met the other werewolf's attack head-on. Their angry snarls echoed like thunder off the trees. The black and white scrapsthe remains of Jacob's clothesfluttered to the ground where he'd disappeared. â€Å"Jacob!† I screamed again, staggering forward. â€Å"Stay where you are, Bella,† Sam ordered. It was hard to hear him over the roar of the fighting wolves. They were snapping and tearing at each other, their sharp teeth flashing toward each other's throats. The Jacob-wolf seemed to have the upper handhe was visibly bigger than the other wolf, and it looked like le was stronger, too. He rammed his shoulder against the gray wolf again and again, knocking him back toward the trees. â€Å"Take her to Emily's,† Sam shouted toward the other boys, who were watching the conflict with rapt expressions. Jacob had successfully shoved the gray wolf off the road, and they were disappearing into the forest, though the sound of their snarls was still loud. Sam ran after them, kicking off his shoes on the way. As he darted into the trees, he was quivering from head to toe. The growling and snapping was fading into the distance. Suddenly, the sound cut off and it was very quiet on the road. One of the boys started laughing. I turned to stare at himmy wide eyes felt frozen, like I couldn't even blink them. The boy seemed to be laughing at my expression. â€Å"Well, there's something you don't see every day,† he snickered. His face was vaguely familiarthinner than the others Embry Call. â€Å"I do,† the other boy, Jared, grumbled. â€Å"Every single day.† â€Å"Aw, Paul doesn't lose his temper every day,† Embry disagreed, still grinning. â€Å"Maybe two out of three.† Jared stopped to pick something white up off the ground. He held it up toward Embry; it dangled in limp strips from his hand. â€Å"Totally shredded,† Jared said. â€Å"Billy said this was the last pair he could affordguess Jacob's going barefoot now.† â€Å"This one survived,† Embry said, holding up a white sneaker. â€Å"Jake can hop,† he added with a laugh. Jared started collecting various pieces of fabric from the dirt. â€Å"Get Sam's shoes, will you? All the rest of this is headed for the trash.† Embry grabbed the shoes and then jogged into the trees where Sam had disappeared. He was back in a few seconds with a pair of cut-off jeans draped over his arm. Jared gathered the torn remnants of Jacob's and Paul's clothes and wadded them into a ball. Suddenly, he seemed to remember me. He looked at me carefully, assessing. â€Å"Hey, you're not going to faint or puke or anything?† he demanded. â€Å"I don't think so,† I gasped. â€Å"You don't look so good. Maybe you should sit down.† â€Å"Okay,† I mumbled. For the second time in one morning, I put my head between my knees. â€Å"Jake should have warned us,† Embry complained. â€Å"He shouldn't have brought his girlfriend into this. What did he expect?† â€Å"Well, the wolf's out of the bag now.† Embry sighed. â€Å"Way to go, Jake.† I raised my head to glare at the two boys who seemed to be taking this all so lightly. â€Å"Aren't you worried about them at all?† I demanded. Embry blinked once in surprise â€Å"Worried? Why?† â€Å"They could hurt each other!† Embry and Jared guffawed. â€Å"I hope Paul gets a mouthful of him,† Jared said. â€Å"Teach him a lesson.† I blanched. â€Å"Yeah, right!† Embry disagreed. â€Å"Did you see Jake? Even Sam couldn't have phased on the fly like that. He saw Paul losing it, and it took him, what, half a second to attack? The boy's got a gift.† â€Å"Paul's been fighting longer. I'll bet you ten bucks he leaves a mark.† â€Å"You're on. Jake's a natural. Paul doesn't have a prayer.† They shook hands, grinning. I tried to comfort myself with their lack of concern, but I couldn't drive the brutal image of the fighting werewolves from my head. My stomach churned, sore and empty, my head ached with worry. â€Å"Let's go see Emily. You know she'll have food waiting.† Embry looked down at me. â€Å"Mind giving us a ride?† â€Å"No problem,† I choked. Jared raised one eyebrow. â€Å"Maybe you'd better drive, Embry. She still looks like she might hurl.† â€Å"Good idea. Where are the keys?† Embry asked me. â€Å"Ignition.† Embry opened the passenger-side door. â€Å"In you go,† he said cheerfully, hauling me up from the ground with one hand and stuffing me into my seat. He appraised the available space. â€Å"You'll have to ride in the back,† he told Jared. â€Å"That's fine. I got a weak stomach. I don't want to be in there when she blows.† â€Å"I bet she's tougher than that. She runs with vampires.† â€Å"Five bucks?† Jared asked. â€Å"Done. I feel guilty, taking your money like this.† Embry got in and started the engine while Jared leapt agilely into the bed. As soon as his door was closed, Embry muttered to me, â€Å"Don't throw up, okay? I've only got a ten, and if Paul got his teeth into Jacob† â€Å"Okay,† I whispered. Embry drove us back toward the village. â€Å"Hey, how did Jake get around the injunction anyway?† â€Å"The what?† â€Å"Er, the order. You know, to not spill the beans. How did he tell you about this?† â€Å"Oh, that,† I said, remembering Jacob trying to choke out the truth to me last night. â€Å"He didn't. I guessed right.† Embry pursed his lips, looking surprised. â€Å"Hmm. S'pose that would work.† â€Å"Where are we going?† I asked. â€Å"Emily's house. She's Sam's girlfriend no, fiancee, now, I guess. They'll meet us back there after Sam gives it to them for what just happened. And after Paul and Jake scrounge up some new clothes, if Paul even has any left.† â€Å"Does Emily know about ?† â€Å"Yeah. And hey, don't stare at her. That bugs Sam.† I frowned at him. â€Å"Why would I stare?† Embry looked uncomfortable. â€Å"Like you saw just now, hanging out around werewolves has its risks.† He changed the subject quickly. â€Å"Hey, are you okay about the whole thing with the black-haired bloodsucker in the meadow? It didn't look like he was a friend of yours, but. .† Embry shrugged. â€Å"No, he wasn't my friend.† â€Å"That's good. We didn't want to start anything, break the treaty, you know.† â€Å"Oh, yeah, Jake told me about the treaty once, a long time ago. Why would killing Laurent break the treaty?† â€Å"Laurent,† he repeated, snorting, like he was amused the vampire had had a name. â€Å"Well, we were technically on Cullen turf. We're not allowed to attack any of them, the Cullens, at least, off our landunless they break the treaty first. We didn't know if the black-haired one was a relative of theirs or something. Looked like you knew him.† â€Å"How would they go about breaking the treaty?† â€Å"If they bite a human. Jake wasn't so keen on the idea of letting it go that far.† â€Å"Oh. Um, thanks. I'm glad you didn't wait.† â€Å"Our pleasure.† He sounded like he meant that in a literal sense. Embry drove past the easternmost house on the highway before turning off onto a narrow dirt road. â€Å"Your truck is slow,† he noted. â€Å"Sorry.† At the end of the lane was a tiny house that had once been gray. There was only one narrow window beside the weathered blue door, but the window box under it was filled with bright orange and yellow marigolds, giving the whole place a cheerful look. Embry opened the truck door and inhaled. â€Å"Mmm, Emily's cooking.† Jared jumped out of the back of the truck and headed for the door, but Embry stopped him with one hand on his chest. He looked at me meaningfully, and cleared his throat. â€Å"I don't have my wallet on me,† Jared said. â€Å"That's okay. I won't forget.† They climbed up the one step and entered the house without knocking. I followed timidly after them. The front room, like Billy's house, was mostly kitchen. A young woman with satiny copper skin and long, straight, crow-black hair was standing at the counter by the sink, popping big muffins out of a tin and placing them on a paper plate. For one second, I thought the reason Embry had told me not to stare was because the girl was so beautiful. And then she asked â€Å"You guys hungry?† in a melodic voice, and she turned to face us full on, a smile on half of her face. The right side of her face was scarred from hairline to chin by three thick, red lines, livid in color though they were long healed. One line pulled down the corner of her dark, almond-shaped right eye, another twisted the right side of her mouth into a permanent grimace. Thankful for Embry's warning, I quickly turned my eyes to the muffins in her hands. They smelled wonderfullike fresh blueberries. â€Å"Oh,† Emily said, surprised. â€Å"Who's this?† I looked up, trying to focus on the left half of her face. â€Å"Bella Swan,† Jared told her, shrugging. Apparently, I'd been a topic of conversation before. â€Å"Who else?† â€Å"Leave it to Jacob to find a way around,† Emily murmured. She stared at me, and neither half of her once-beautiful face was friendly. â€Å"So, you're the vampire girl.† I stiffened. â€Å"Yes. Are you the wolf girl?† She laughed, as did Embry and Jared. The left half of her face warmed. â€Å"I guess I am.† She turned to Jared. â€Å"Where's Sam?† â€Å"Bella, er, surprised Paul this morning.† Emily rolled her good eye. â€Å"Ah, Paul,† she sighed. â€Å"Do you think they'll be long? I was just about to start the eggs.† â€Å"Don't worry,† Embry told her. â€Å"If they're late, we won't let anything go to waste.† Emily chuckled, and then opened the refrigerator. â€Å"No doubt,† she agreed. â€Å"Bella, are you hungry? Go ahead and help yourself to a muffin.† â€Å"Thanks.† I took one from the plate and started nibbling around the edges. It was delicious, and it felt good in my tender stomach. Embry picked up his third and shoved it into his mouth whole. â€Å"Save some for your brothers,† Emily chastised him, hitting him on the head with a wooden spoon. The word surprised me, but the others thought nothing of it. â€Å"Pig,† Jared commented. I leaned against the counter and watched the three of them banter like a family. Emily's kitchen was a friendly place, bright with white cupboards and pale wooden floorboards. On the little round table, a cracked blue-and-white china pitcher was overflowing with wildflowers. Embry and Jared seemed entirely at ease here. Emily was mixing a humongous batch of eggs, several dozen, in a big yellow bowl. She had the sleeves of her lavender shirt pushed up, and I could see that the scars extended all the way down her arm to the back of her right hand. Hanging out with werewolves truly did have its risks, just as Embry had said. The front door opened, and Sam stepped through. â€Å"Emily,† he said, and so much love saturated his voice that I felt embarrassed, intrusive, as I watched him cross the room in one stride and take her face in his wide hands. He leaned down and kissed the dark scars on her right cheek before he kissed her lips. â€Å"Hey, none of that,† Jared complained. â€Å"I'm eating.† â€Å"Then shut up and eat,† Sam suggested, kissing Emily's ruined mouth again. â€Å"Ugh,† Embry groaned. This was worse than any romantic movie; this was so real that it sang out loud with joy and life and true love. I put my muffin down and folded my arms across my empty chest. I stared at the flowers, trying to ignore the utter peace of their moment, and the wretched throbbing of my wounds. I was grateful for the distraction when Jacob and Paul came through the door, and then shocked when I saw that they were laughing. While I watched, Paul punched Jacob on the shoulder and Jacob went for a kidney jab in return. They laughed again. They both appeared to be in one piece. Jacob scanned the room, his eyes stopping when he found me leaning, awkward and out of place, against the counter in the far corner of the kitchen. â€Å"Hey, Bells,† he greeted me cheerfully. He grabbed two muffins as he passed the table and came to stand beside me. â€Å"Sorry about before,† he muttered under his breath. â€Å"How are you holding up.'† â€Å"Don't worry, I'm okay. Good muffins.† I picked mine back up and started nibbhrg again. My chest felt better as soon as Jacob was beside me. â€Å"Oh, man!† Jared wailed, interrupting us. I looked up, and he and Embry were examining a fading pink line on Paul's forearm. Embry was grinning, exultant. â€Å"Fifteen dollars,† he crowed. â€Å"Did you do that?† I whispered to Jacob, remembering the bet. â€Å"I barely touched him. He'll be perfect by sundown.† â€Å"By sundown?† I looked at the line on Paul's arm. Odd, but it looked weeks old. â€Å"Wolf thing,† Jacob whispered. I nodded, trying to not look weirded out. â€Å"You okay?† I asked him under my breath. â€Å"Not a scratch on me.† His expression was smug. â€Å"Hey, guys,† Sam said in a loud voice, interrupting all the conversations going on in the small room. Emily was at the stove, scraping the egg mixture around a big skillet, but Sam still had one hand touching the small of her back, an unconscious gesture. â€Å"Jacob has information for us.† Paul looked unsurprised. Jacob must have explained this to him and Sam already. Or they'd just heard his thoughts. â€Å"I know what the redhead wants.† Jacob directed his words toward Jared and Embry. â€Å"That's what I was trying to tell you before.† He kicked the leg of the chair Paul had settled into. â€Å"And?† Jared asked. Jacob's face got serious. â€Å"She is trying to avenge her mateonly it wasn't the black-haired leech we killed. The Cullens got her mate last year, and she's after Bella now.† This wasn't news to me, but I still shivered. Jared, Embry, and Emily stared at me with open-mouthed surprise. â€Å"She's just a girl,† Embry protested. â€Å"I didn't say it made sense. But that's why the bloodsucker's been trying to get past us. She's been heading for Forks.† They continued to stare at me, mouths still hanging open, for a long moment. I ducked my head. â€Å"Excellent,† Jared finally said, a smile beginning to pull up the corners of his mouth. â€Å"We've got bait.† With stunning speed, Jacob yanked a can opener from the counter and launched it at Jared's head. Jared's hand flicked up faster than I would have thought possible, and he snagged the tool just before it hit his face. â€Å"Bellais not bait.† â€Å"You know what I mean,† Jared said, unabashed. â€Å"So we'll be changing oar patterns,† Sam said, ignoring their squabble. â€Å"We'll try leaving a few holes, and see if she falls for it. We'll have to split up, and I don't like that. But if she's really after Bella, she probably won't try to take advantage of our divided numbers.† â€Å"Quit's got to be close to joining us,† Embry murmured. â€Å"Then we'll be able to split evenly.† Everyone looked down. I glanced at Jacob's face, and it was hopeless, like it had been yesterday afternoon, outside his house. No matter how comfortable they seemed to be with their fate, here in this happy kitchen, none of these werewolves wanted the same fate for their friend. â€Å"Well, we won't count on that,† Sam said in a low voice, and then continued at his regular volume. â€Å"Paul, Jared, and Embry will take the outer perimeter, and Jacob and I will take the inner. We'll collapse in when we've got her trapped.† I noticed that Emily didn't particularly like that Sam would be in the smaller grouping. Her worry had me glancing up at Jacob, worrying, too. Sam caught my eye. â€Å"Jacob thinks it would be best if you spent as much time as possible here in La Push. She won't know where to find you so easily, just in case.† â€Å"What about Charlie?† I demanded. â€Å"March Madness is still going,† Jacob said. â€Å"I think Billy and Harry can manage to keep Charlie down here when he's not at work.† â€Å"Wait,† Sam said, holding one hand up. His glance flickered to Emily and then back to me. â€Å"That's what Jacob thinks is best, but you need to decide for yourself. You should weigh the risks of both options very seriously. You saw this morning how easily things can get dangerous here, how quickly they get out of hand. If you choose to stay with us, I can't make any guarantees about your safety.† â€Å"I won't hurt her,† Jacob mumbled, looking down. Sam acted as if he hadn't heard him speak. â€Å"If there was somewhere else you felt safe† I bit my lip. Where could I go that wouldn't put someone else in danger? I recoiled again from the idea of bringing Renee into thispulling her into the circle of the target I wore â€Å"I don't want to lead Victoria anywhere else,† I whispered. Sam nodded. â€Å"That's true. It's better to have her here, where we can end this.† I flinched. I didn't want Jacob or any of the rest of them trying to end Victoria. I glanced at Jake's face; it was relaxed, almost the same as I remembered it from before the onset of the wolf thing, and utterly unconcerned by the idea of hunting vampires. â€Å"You'll be careful, right?† I asked, an audible lump in my throat. The boys burst into loud hoots of amusement. Everyone laughed at meexcept Emily. She met my eyes, and I could suddenly see the symmetry underlying her deformity. Her face was still beautiful, and alive with a concern even more fierce than mine. I had to look away, before the love behind that concern could start me aching again. â€Å"Food's ready,† she announced then, and the strategic conversation was history. The guys hurried to surround the tablewhich looked tiny and in danger of being crushed by themand devoured the buffet-sized pan of eggs Emily placed in their midst in record time. Emily ate leaning against the counter like meavoiding the bedlam at the tableand watched them with affectionate eyes. Her expression clearly stated that this was her family. All in all, it wasn't exactly what I'd been expecting from a pack of werewolves. I spent the day in La Push, the majority of it in Billy's house. He left a message on Charlie's phone and at the station, and Charlie showed up around dinnertime with two pizzas. It was good he brought two larges; Jacob ate one all by himself. I saw Charlie eyeing the two of us suspiciously all night, especially the much-changed Jacob. He asked about the hair; Jacob shrugged and told him it was just more convenient. I knew that as soon as Charlie and I were headed home, Jacob would take offoff to run around as a wolf, as he had done intermittently through the entire day. He and his brothers of sorts kept up a constant watch, looking for some sign of Victoria's return. But since they'd chased her away from the hot springs last nightchased her halfway to Canada, according to Jacobshe'd yet to make another foray. I had no hope at all that she might just give up. I didn't have that kind of luck. Jacob walked me to my truck after dinner and lingered by the window, waiting for Charlie to drive away first. â€Å"Don't be afraid tonight,† Jacob said, while Charlie pretended to be having trouble with his seat belt. â€Å"We'll be out there, watching.† â€Å"I won't worry about myself,† I promised. â€Å"You're silly. Hunting vampires is fun. It's the best part of this whole mess.† I shook my head. â€Å"If I'm silly, then you're dangerously unbalanced.† He chuckled. â€Å"Get some rest, Bella, honey. You look exhausted.† â€Å"I'lltry.† Charlie honked his horn impatiently. â€Å"See you tomorrow,† Jacob said. â€Å"Come down first thing.† â€Å"Iwill.† Charlie followed me home. I paid scant attention to the lights in my rearview mirror. Instead, I wondered where Sam and Jared and Embry and Paul were, out running in the night. I wondered if Jacob had joined them yet. When we got home, I hurried for the stairs, but Charlie was right behind me. â€Å"What's going on, Bella?† he demanded before I could escape. â€Å"I thought Jacob was part of a gang and you two were fighting.† â€Å"We made up.† â€Å"And the gang?† â€Å"I don't knowwho can understand teenage boys? They're a mystery. But I met Sam Uley and his fiancee, Emily. The seemed pretty nice to me.† I shrugged. â€Å"Must have all been a misunderstanding.† His face changed. â€Å"I hadn't heard that he and Emily had made it official. That's nice. Poor girl.† â€Å"Do you know what happened to her?† â€Å"Mauled by a bear, up north, during salmon spawning seasonhorrible accident It was more than a year ago now. I heard Sam was really messed up over it.† â€Å"That's horrible,† I echoed. More than a year ago. I'd bet that meant it had happened when there was just one werewolf in La Push. I shuddered at the thought of how Sam must have felt every time he looked at Emily's face. That night, I lay awake for a long time trying to sort through the day. I worked my way backward through dinner with Billy, Jacob, and C harlie, to the long afternoon in the Blacks' house, waiting anxiously to hear something from Jacob, to Emily's kitchen, to the horror of the werewolf fight, to talking with Jacob on the beach. I thought about what Jacob had said early this morning, about hypocrisy. I thought about that for a long time. I didn't like to think that I was a hypocrite, only what was the point of lying to myself? I curled into a tight ball. No, Edward wasn't a killer. Even in his darker past, he'd never been a murderer of innocents, at least. But what if he had been? What if, during the time I that I'd known him, he'd been just like any other vampire? What if people had been disappearing from the woods, just like now? Would that have kept me away from him? I shook my head sadly. Love is irrational, I reminded myself. The more you loved someone, the less sense anything made. I rolled over and tried to think of something elseand I thought of Jacob and his brothers, out running in the darkness. I fell asleep imagining the wolves, invisible in the night, guarding me from danger. When I dreamed, I stood in the forest again, but I didn't wander. I was holding Emily's scarred hand as we faced into the shadows and waited anxiously for our werewolves to come home.

Friday, August 30, 2019

Health Promotion in Nursing Practice Essay

Health promotion is defined by the world health organization as the process of enabling people to increase control over, and to improve, their health. It moves beyond a focus on individual behavior towards a wide range of social and environmental interventions. The purpose of health promotion is to empower people to improve their health and delay disease, disability, and death. The nurses plays an important role in health-promoting activities which include educating people in making important life changing decision such as healthy eating, stress management, adequate physical activity, adequate sleep and not smoking. Achieving optimal health is not the sole responsibility of the individual the government are also involved in health promotion by creating safe environment free of pollution, safe drinkable water, provide vaccines for preventable diseases. Health differences can be reduced by providing culturally relevant health information, programs, and services, creating public policy that promotes health, improving access to health care and providing other opportunities for making healthy choices. Primary prevention is the prevention of diseases and conditions before their biological onset. This can be achieve in many ways, such as educating individuals to decrease risk taking behaviors, preventing environmental exposures, environmental health measures, such as maintaining a safe water and food supply. Educating individuals on sex educations such as promoting the use of condoms, abstinence before marriage, avoiding multiple sex partners will prevent sexual transmitted diseases such as HIV, and also reduce the risk of cervical cancer in women. Education in healthy eating habit and increase in physical activity will reduce obesity and prevent some diseases associated with obesity such as hypertension, type 2 diabetes, heart related conditions etc. Vaccines are good examples of primary prevention measures, many diseases today have been prevented with the use of vaccines. Good example of secondary prevention in the hospital settings is offering of flu vaccine and pneumonia vaccine to all discharged patient who meets the criteria. Education on the use of seat belt will reduce the degree of automobile injuries. Secondary prevention is the process of identifying the presence of disease in the body at an early stage when it has not advanced to the point of causing any signs, symptoms or disability . These preclinical conditions are most often discovered by disease screening. Screenings such as routine mammograms, Pap smear, colonoscopy, PSA, prevents disease emergence and this usually leads prevention of serious complications. Secondary preventions also includes routine blood works to check for cholesterol level, prescreening for hypertension, screening for high blood-lead level for people who work in environment with lead exposure. Nurses should promote secondary prevention in our area of work, in the communities; they should emphasis on the importance of health screenings to the clients in their area of profession. The government should also provide funds for secondary prevention by providing resources for free screening in public places like the school, church, hospitals, town hall etc. With secondary prevention there will be delay in disease progression, disability and death. Tertiary prevention is the prevention of disease progression and complication after it has been clinically diagnosed. This includes the rehabilitation and management of the disease , example of tertiary prevention is the routine screening for and management of diabetic associated conditions in a diabetic patient such as renal ,eye, and foot problems. Eliminating offending allergens from asthmatic patients. Preventing reoccurrence of myocardial infarction with blood thinners such as aspirin, Plavix etc. The use of physical therapist and occupational therapist to regain physical function in a stroke patient. Nurses in their different area of nursing plays important roles in health promotion, it could be by primary prevention, secondary prevention, or tertiary prevention. When a patient is admitted in the hospital it is the duty of the nurses to educate the patient and the family on the tertiary prevention level on how to manage his disease such as to comply with ordered medication, diet modifications, smoking cessation etc. Educational handouts with specific teaching on disease prevention and management should be given to patient upon discharge.In conclusion primary prevention is the most important preventive measure in health promotion, while secondary prevention is very vital in health promotion as with this preventive measure there is a high chance of a positive outcome. Also tertiary prevention is also very important as it minimizes complication and delay death. References Robert, R. B. (2002). Encyclopedia of Public Health.Retrieved on January 13, 2013 from GCU Library.Retrieved on January 13, 2013 from www.who.int/topics/health_promotion.

Thursday, August 29, 2019

Marketing - Analyzing Buyer Behavior Essay Example | Topics and Well Written Essays - 750 words

Marketing - Analyzing Buyer Behavior - Essay Example Floor care products are majorly bought by women who range between 36 to 50 years who are married and take care of their dwellings. Women are majorly concerned about the cleanliness at home and aim at buying products that maintain hygiene at nominal price. As women in today's world are equal bread earners, they are independent to make purchase decisions. The consumer product proposal is good. As mentioned, there must be a new product line improved as a new market strategy to attract new customers and also to retain the existing customer by providing them different options. The new product line must concentrate more on the price and efficacy than the eco friendly and safety aspects of it. As the price factor is the priority of the customers, there has to be a relatively decrease in price for the product to compete with the existing products in the market. By decreasing the manufacturing cost and also reducing the cost of the product, there can be an increase in the volume of goods sold in the market and it will reach the customers effectively. Higher the volume of sales, greater is the profit. These new products can be marketed to mass merchandises like Walmart and K mart in their premier shelves as the inflow of people on a daily basis is very high and people believe in their prices and products. Expanding in to other retail sectors are also a good strategic move, as they can attract a different set of new customers and is a good market development. Expanding in to new sector will familiarize the product and brand in the market. The marketing strategies like online sales will be an added advantage as people now adays prefer online buying which is very comfortable. Online buying has become one o the most common ways of purchasing a products since the last decade. Online sales have doubled during the past two years, with 53 percent of US Web users saying they have made interactive purchases so far in 1999. ("Pastore", 1999) There can be few more consumer recommendations like anti bacterial product which prevents floor from infections, easy usage of the products by providing free liquid sprays, refreshing fragrant liquid, easy stain removal sprays etc. The proposal for commercial product is good; it has aimed at diversifying its supply areas to hospital and nursing homes as the hospitality industry is untapped. The commercial proposal will definitely work because of the increase in span of supply to other commercial sectors and concentrating on the pricing strategy. Whether it is an individual or an organization, they look at optimization of the product and a better value for money. When a product is sold at a nominal cost in the market and is also efficient, it has a better market penetration. A private label floor cleaner will be a good growth strategy as it will have good market development. The health care sector has a high concern for cleanliness and hygiene. It can be observed from any health care organization that there is a high level of abidance for cleanliness. There will be a house keeper who will keep cleaning the floor for at least five to ten times in a day. Their usage is also high where there is a high volume sales opportunity. Adding

Wednesday, August 28, 2019

Reflective Assessment Research Paper Example | Topics and Well Written Essays - 500 words

Reflective Assessment - Research Paper Example In 2oo4, IDEA has proclaimed that children with disabilities learn more efficiently with the assistance of technology and services (Dalton, 2006). AT has not only facilitated the special needs students, but it has also contributed positively in enhancing and developing the restrained abilities of children belonging from different regions and cultures. The change in the structure of teaching method and delivery of instructions by IDEA, further recommend to the educators to be aware of the significance of AT in Education. Teachers develop, monitor, generate and deliver instructions by keeping in regard the grasping ability of students and eventually engaging them into learning process. Thus, the resources (AT) becomes more comprehend able and accessible to those who do not posses any disability or their disability has not been identified yet. The difference between IT (Instructional Technology) and AT (Assistive Technology) is often misunderstood. The awareness of human learning process linked to the task of teaching and learning is known as Instructional Technology. To evaluate the purpose of IT, the probable outcomes like instructional usefulness, instructional appeal and instructional competence is taken into consideration. Therefore, the above mentioned tools are necessary for the planning required, for instructional interventions, and the requirement of AT devices and sources according to the subject or concept. Deficiency of reading can be taken into regard as a skill and as a mean to attain information. When children with special needs use special software, developed to assist them learn phonetic pronunciation, recognition and fluency, they come into the category of IT in education. On the other hand, if the software provides audio textual information to enhance the information specifically related to the subject then it is a part of AT (Parette & Peters, 2007). Experts have highlighted the need to assess the difference between

Tuesday, August 27, 2019

Managing Markets Essay Example | Topics and Well Written Essays - 6000 words

Managing Markets - Essay Example One of the top ten leading financial investing companies in the world is the Barclays Banks and their investors. It is financial institutional investor company and a large liaison which can be traced back to a self-effacing business founded more than three hundred years ago in the heart of London’s financial region. It is a UK-based financial services group connected principally in banking, investment banking and investment organization. In terms of market capitalization Barclays is one of the top ten leading banks in the globe. A primary UK retail and industry bank, it also offers corresponding global services to international corporations and financial institutions globally. It has been engaged in banking for over years and functions in over sixty countries with more than 76,200 employees. On June 30, 2004, the group attained a pre-tax profit of 2,411 million pounds. Investors’ funds were 17.1 billion pounds and the Tier 1 assets relative amount was 7.7 % (Barclays Global Investors, 2004). It is also engrossed in societal educational associations, situation, arts, disability and social insertion. Nowadays, Barclays has full-grown from a group of English companies to a global bank symbolized in Europe, Middle East , United States of America, Africa, the Caribbean, Latin America, Asia, and Australasia. Barclays Bank is one of the world’s biggest asset managers and a top global provider of investment organization products and services (Barclays Global Investors, 2004). It provides structured investment methods such as indexing which is regard as to be submissive and yet is being covenant with vigorous investors, strategic asset distribution and risk-controlled active products. It also offers connected investment services such as cash management, securities lending and portfolio conversion services. Moreover, Barclays Banks is the product and service leader in Exchange Traded Funds (ishares), with over 100 funds for financial

Monday, August 26, 2019

The Reaction of Faculty Staff to Resident`s Feedback on Their Teaching Essay

The Reaction of Faculty Staff to Resident`s Feedback on Their Teaching Performance - Essay Example The abstract is well drafted, and it has outlined the methods used and the main findings. The research would have more information present the research problem clearly. It is not clear from the abstract where the research problem. It has stated the aim of the research paper which is to increase understanding on how the reaction of faculty staff to resident`s feedback on their teaching performance. It would be in helping to include a recommendation in this paper in order to know the next step of action. The paper presents two research objectives that are later structured into research questions. The research objectives that were structured by research questions are: how the faculty staff proceeds on receiving feedback and the factors that influence on their progression (Van der Leeuw 2011, p.2). The objectives seem to look at the progress after the feedback. The aim was to increase understanding in the reaction to feedback. The objectives should be in line with the objective of the study. The inclusion of an objective that explores more on how the nature of the feedback makes the faculty react would help create more insight. The research questions give the direction to be followed during the research process. The research problem is clearly stated, and it gives the rationale for the study, then there is a reliable system in place that provides feedback. The issue is responsiveness of the faculty staff to the feedback. This agrees with the work of Steinert et al. (2006, p. 498) that stated that the change in teaching behaviors after feedback was not frequently researched on. The literature is up to date as most of the references were recently giving information of the recent advances.

Sunday, August 25, 2019

Top Of The Rock Production Research Paper Example | Topics and Well Written Essays - 2000 words

Top Of The Rock Production - Research Paper Example At present, Frost productions is engaged in lightening, audio, video dà ©cor, staging, venue spot light and media services (Frost Productions, 2013b; Frost Productions, 2013c). Mission and goals are the building blocks of an organization. They guide the actions of an organization and define the goals and objectives. Whether an organization is big or small, having a mission is the first step for setting up a business. Frost production was established as a lighting company in New York. The company quickly expanded its base to other cities and very soon became a pioneer in event management. The mission of the company is to provide distinctive and unique event experience to the client. The company aims to provide excellent service in managing the overall execution of events. In the current scenario, the company aims to organize an international live music on the local grounds of Guam. The company has decided to bring in top performing artists on this island and with the participation of international companies and local vendors, make this a successful event (Ekeledo & Sivakumar, 2004). In the present situation, the company is concerned with finding a suitable fairground for organizing the event. The goal of the event company is to offer the best quality event at a reasonable cost for the general public. The event organization aims to host local as well as international programs for artists four times in a year, with the objective of gaining reputation and providing best choices for the islanders. Frost Productions aims to organize best food, refreshments and music available to the consumers. Core competencies can be described as the strategic advantages or the main strengths of an organization or a business. Core competencies or core capabilities of an organization are the tangible and intangible resources which differentiates an organization from its competitors as well as the overall market (Courtney, Navarro & OHare, 2007, pp.34–46). Core competencies of an

Social Entrepreneurship Essay Example | Topics and Well Written Essays - 2250 words

Social Entrepreneurship - Essay Example es mainly address the social needs in the society through offering products and services that aim at meeting the cultural, social and environmental needs in the society (Paton, 2003 p. 89). The bank commenced operations in 1984 providing trade union banking services while observing the founding principles. The trade unions offered provided equity capital of 1.25 million pounds while the Co-operative Bank added 2.6 million pounds to the start up capital. In the first year, the bank operated as a licensed deposit taking institution providing its clients a range of banking services. In the first year, the balance sheet figures in terms of assets grew to over 40 million pounds with the deposits reaching 35 million pounds. The Bank offered a rights issue in 1986 thus enabling more trade unions to buy shares. Fifty-eight trade unions were now members of the bank. After the passage of Public services (social value) Act 2012, Birmingham has experienced the emergence of many social enterprise s. The Act enables the stakeholders to become members of the social enterprises and introduces several tools for the identification of the social impact (Price, 2009 P. 52). The major responsibilities of social enterprises include encouraging community involvement, encouraging of equal opportunities and supporting a green economy. Social enterprises should also encourage sustainability initiatives like recycling and encourage fair trading practices (Doherty & Thompson, 2006 p.40). Social enterprise based organisations have innovative and people-friendly solutions that aim at creating positive change in the society unlike the traditional corporate world that is geared at profit maximisation (Nicholls, 2006 p.18). Most social enterprise based organisations work with poor communities and provides the staff with flexible working schedules. According to the UK department of Trade and Industry (DTI), socially based enterprises have primary social objectives whereby the surplus is reinvested

Saturday, August 24, 2019

Herman Melville Research Paper Example | Topics and Well Written Essays - 1500 words

Herman Melville - Research Paper Example Library of Congress would then honor him for he actually was the library’s first writer to collect and publish material. The great author was born in the city of New York as the third born child of Maria and Allan Gansevoort Melville. The letter e was added to his family name to making it Melville in the year 1832 by Maria on the death of his father. While growing up, young Melville was attacked by scarlet fever in the mid 1820s which adversely affected his health. Whereas he regained back his health after a short period, the disease permanently impaired Millville’s eyesight. The father was a very accomplished and successful merchant & importer and as such the family led a very good life when Melville was growing. However things changed in the year 1830 when Allan unsuccessfully attempted to enter fur trade. This failure spelt doom for the family’s fortune on his death in the year 1832, Allan left the family in an extremely desperate financial situation. Following the father’s demise, Herman Melville’s oldest brother Gansevoort took over their family business in New York City. Soon after, Melville joined Gansevoort in the business as a partner and later some of their brothers came on board. Melville would enrol with Albany Classical School in the mid 1830s to study literature and while at Albany he participated in the student debates. At the same time he had started his writing career; he wrote some proems short stories and essays. After a period of studies at the Albany Classical School Melville left and took up a job as a teacher in Massachusetts. The teaching job was not fulfilling and therefore after just three months of work, Melville quit his position and returned to New York City. The year 1837 was another bad one for the family, Gansevoort’s business of fur and cap went down again this time round putting the family in a

Friday, August 23, 2019

Jackson Pollock and Modern Art Essay Example | Topics and Well Written Essays - 1000 words

Jackson Pollock and Modern Art - Essay Example The essay "Jackson Pollock and Modern Art" explores the art of Jackson Pollock and his impact in the context of Modern Art. He was â€Å"a roughshod, ill-mannered, prodigiously ambitious, aggressive, alcoholic, tormented artist .† This image is important to an interpretation of the apparently chaotic nature of much of Pollock’s works, and the technique that led to them. However, as is often the case with creative artists of all sorts, and particularly painters such as Pollock, there was a method to his madness. As Toynton has pointed out, films of Pollock creating his paintings clearly show that even the most abstract of them start as figurative works and only move into the abstract as they develop.Pollock moved his canvas from the easel to the floor, thus enabling him to work on much larger canvases with greater ease than before, and also to see them from multiple points of view. In one revealing statement he talked about his technique and why he used it: My painting d oes not come from the easel. I hardly ever stretch the canvas before painting. I prefer to tack the unstretched canvas to the hard wall or the floor. I need the resistance of a hard surface. On the floor I am more at ease. I feel nearer, more part of the painting, since this way I can walk around it, work from the four sides and literally be in the painting. It is interesting to note that Pollock takes an intense and yet casual approach to his painting. Thus the fact that he does not go through the often laborious process. of stretching the canvas before painting on it, but rather merely tacking it to a wall or floor illustrates the casual, almost primitive method of preparation. At the same time Pollock becomes more intensely involved with the painting, as if he were actually a part of it: I continue to get further away from the usual painter's tools such as easel, palette, brushes, etc. I prefer sticks, trowels, knives and dripping fluid paint or a heavy impasto with sand, broken glass or other foreign matter added. When I am in my painting, I'm not aware of what I'm doing. It is only after a sort of 'get acquainted' period that I see what I have been about. I have no fear of making changes, destroying the image, etc., because the painting has a life of its own. I try to let it come through. It is only when I lose contact with the painting that the result is a mess. Otherwise there is pure harmony, an easy give and take, and the painting comes out well. (Varnedoe, 23) The idea of being "in" the painting is of course hardly new to Pollock, but the fact that his technique apparently fitted into his emotional and intellectual attachment to the painting is. His physical technique: standing on and thus within the painting, had a profound effect both upon his creations and upon generations of creative artists in general and painters in particular, for years both during and after his lifetime. Pollock hinted, although never explicitly stated, that he was influenced by Native American sand paintings, which are made by trickling thin lines of colored sand onto a flat surface. After WWII, in 1947 Pollock began what he called his "action paintings", which were at least partially informed by the surrealist ideas of "psychic automatism". This automatism was meant to be a direct expression of the unconscious. A direct expression of something which is, by definition, unknowable to the conscious mind might seem a

Thursday, August 22, 2019

Life and Works of Rizal Essay Example for Free

Life and Works of Rizal Essay He continued his studies at the Universidad Central de Madrid, Spain, where he earned the degree of Licientiate in Medicine. He also attended the University of Paris in France and earned second doctorate at the University of Heidelberg in Germany. Having travelled the world extensively, Rizal became conversant in at least twenty-two languages. He was a prolific poet, essayist, diarist, correspondent, and novelist whose most famous works were his two novels, Noli me Tangere and El Filibusterismo. These works fearlessly exposed the injustices committed by the Spanish civil and clerical officials in the Philippines amd spurred the militancy of armed revolutionaries and reformist against more than 300 years of Spanish rule. Rizal was proponent of institutional reforms by peaceful means rather than violence revolution. But he was associated with the growing insurgency movement and declared an enemy of the state by the Spanish authorities particularly because of the publication of his novels. He was deported to Dapitan in Zamboanga then incarcerated at Fort Santiago. When the Katipunan exploded into the full-blown revolution, the authorities were quick to incriminate him. After a mock trial, Rizal was convicted and sentence to die by firing squad at Bagubayan on December 30, 1896. Eventually, his martyred death proved to be the catalyst that precipitated the Philippine revolution and the downfall of the Spanish colonial rule.

Wednesday, August 21, 2019

Plan for Outsourcing Payroll

Plan for Outsourcing Payroll This report is aimed at the MD and all stakeholders referencing a proposal for a research project in relation to payroll being outsourced or to bring in house for B W Plant Hire and Sales Ltd A description of the project under research, analysis of good practice in relation to this issue. The identification of key stakeholders. Why the stakeholders would be interested or effected by the study. The key sources from the secondary research The evaluation of the contribution to the study To outline the present findings and inform the stakeholders to act on the results Overview of this research In 2005 there was only 35 people on the payroll, as the company has grown over the years there are now 75 employees, the payroll is outsourced to a local company at a cost of  £4500.00 per annum. In 2010 it was decided to outsource the payroll to save time and money, as there was only one person qualified in payroll. To take the responsibility from the only one person qualified it was decided any person in the accounts office could gather the weekly hours from depot and email to the outsource company. When the reports came back it was checked against the information sent. The correct reports were returned and processed by the office manager. The cost was lower than the company was paying for in house payroll. The software cost was  £1500.00 per annum, the time it took was 2 hours, so it was decided by the MD and the accountants to outsource payroll. In 2014 the payroll was moved to a different outsource at a cheaper rate, as the payroll has grown the cost is now  £5600.00 and growing. The administration of the payroll has become difficult to manage collating the average holiday pay by spreadsheet of the growing number of employees along with the pension information. Correct information is not communicated correctly i.e. national minimum wage increase, apprenticeship wage P32 reports not being sent to the company on time, basically a lack of communication. To start the process of developing a business case to recommend whether to outsource or bring payroll back in house the researcher will conduct a situational analysis to collect information the current system in use, how it works, any overlaps or shortfalls will be noted. When this is completed the investigation of the product ranges and functions available within the budget settings can this begin. The research of the investigation will perceive the benefits and gain evidence of the potential benefits to the company along with the potential costs and show the realistic advantages of outsourcing or in house payroll. There are 4 depots within the company, each depot has a clocking in machine. All weekly paid employees are to clocking and out each day. If an employee goes to a job from home they are to inform the depot manager and have their clock card signed, this is also checked by the tracker information on the vehicle. (It logs the time the vehicle was started) Every Monday morning each depot scans a copy of the clock cards to the Office Manager. As the depot managers, do not check the clock cards for anomalies it falls back on the Office manager to find the relevant information to complete the spreadsheet (appendix 1) As the spreadsheet is keyed it is prone to human error, the depot managers now must add the hours on the clock cards and sign them, they are then checked again by the office manager who then keys them into the spreadsheet. It is again checked by the finance manager. When all the above is complete it is then forwarded to the outsource company by email to collate. Manual tracking in this way is time consuming and prone to human error, resulting in over pay or underpay and time theft. There are deadlines to meet for the weekly payroll, if the correct information is not sent through, there is an element of pressure on the administrator to request the information on time. An image of the formulas used for recording the 12 week average   Ã‚   Good practice Employee costs are the single greatest expense of most Companies. Payroll one of the most important business functions. Payroll is unusually complex. It must be accurate. It must be efficient. It must comply with all the regulations imposed on it at local, national, and international levels. Employee morale and retention is so critical, payroll must do these things while keeping employees satisfied that they will receive their wage with minimal disruption of their workdays. No one-size-fits-all payroll solution exists that solves the very real challenges of managing payroll in todays fast-paced and highly regulated global environment. Establish Discipline and Manage Expectations Ensure that all stakeholders know what to expect from the payroll department. When do, timesheets need to be submitted? Who approves them? Who is notified if an employee goes on leave? When are the monies in the employee`s bank account. Enforce Accountability Make sure all stakeholders are appropriately accountable. Employees need to know what they are responsible for doing; managers likewise. For example, if an employee forgets to clock in the timecard at the beginning of the day, or clock out  Ãƒâ€šÃ‚   at the end of the day, who is responsible for making sure that employee is paid equitably for their time?   What are the consequences of failing to be accountable for meeting payrolls requirements? Who absorbs the cost of having to cut a check in midcycle? Alongside this accountability must come transparency-all steps in the process must be visible to the payroll staff. Perform Rigorous Balances and Audits The demand for accuracy in payroll is rigorous. Balancing, auditing, and segregating of duties is critical. These steps are to ensure minimized error rates, this can also help avoid off-cycle payments. There should be separate duties so the person entering timecard data is not the person who balances the number of timecards with the payments going out. (Due diligence) Then yet another person should audit the data to make sure it is correct. Rethink Control and Compliance in the Age of Outsourcing. Both the importance and complexity of payroll, many Companies are outsourcing either part or all the function. How much-or how little-is outsourced varies tremendously from company to company. The issue is control: how much of it does company need over its payroll data? When payroll is done in-house, its easy to integrate the data into other systems, to slice and dice it different ways, and otherwise make it work to provide value to the business. Given that Employee costs are the single greatest expense of most companies, having this kind of flexibility can be enormously helpful when making decisions about labouring sourcing, for example, deciding where and when to open a new depot. Advantages and disadvantages appendix 2 The researcher should be aware or data protection issues surrounding the implementation of outsourcing payroll. The principles of the Data Protection 1998 Act concerning the processing of personal data, the key rights that the Data Protection Act gives to data subjects, the consequences for companies of breaching the Data Protection Act and the key issues that arise in outsourcing transactions because of the Data Protection Acts requirements. The DPA gives comprehensive rights to data subjects in relation to their data. In relation to outsourcing transactions, the most important rights include: Access to personal data. Prevention of certain kinds of processing. By way of court order, rectification, blocking, deletion and destruction. These rights are generally enforceable against the outsourcing company as data controller rather than against the data processor. Where the outsourcing provider handles personal data on its clients behalf, the client as the data controller should include appropriate provisions in the outsourcing contract to ensure the outsourcing providers collaboration. This includes obligations to: Amend, transfer or delete the data as requested by the client. Notify the client of data access requests or complaints that it receives in relation to the clients data and provide the client with full co-operation in relation to such requests or complaints. The outsourcing company should also include an obligation on the data processor to be notified immediately if any of the following occur: Data gets accidentally deleted or corrupted. Data becomes lost. The outsourcing provider becomes aware that the data is processed unlawfully. This is to ensure that the client can take the necessary steps to address the issue, including notification to the ICO and/or the data subjects if required. (Andrew Dunlop and Uwe Nimscheck, Burges Salmon LLP) Stakeholder Analysis The stakeholders are anyone with an interest in the business. Stakeholders are individuals, groups or organisations that are affected by the activity of the business. Consideration for powerful and supportive stakeholders i.e. Payroll, HR and Finance with high levels of interest must be updated on this project. If the project has a good team and consists of highly regarded and motivated people who enjoy change on board it can then by brought to the attention of other stakeholders with enthusiasm this is turn can overcome obstructions from individuals when engaging in research. This adds trust and the belief, into the smooth running of the project, a bonus for when asking for funding.   For this research this is who is affected indirectly or directly. They include: Directors Managers Staff/Employee Payroll Finance Shareholders HMRC The researcher should be aware of the drivers for the introduction of the payroll outsourcing/ in house process. Operational Driver- cost effectiveness through time efficiency Logical Driver improved performance for demanding employees and managers. Transform Driver- key strategic drivers addressed in the company net profit During the analysis, it is essential that the stakeholders are fully informed or involved and understand the current process and the impact of change it will have on their role. The opportunities and threats for each stakeholder should be identified and managed during the process. Do they need to be informed or are they involved see appendix 3 The finance team are key stakeholders along with payroll and HR. finance need to be aware for budgeting and forecasting purposes and the costs involved evaluated correctly and if it is a viable project to implement. Payroll dept. will be collating the data regardless of payroll being outsourced or not, it must be carried out. HR need to be involved for change management. They understand the importance of strategy, culture and values, this would be advantageous throughout the planning and implementation process. The ethics must be considered when exchanging information especially when using emails, confidentially is a must, along with free and informed consent. Stakeholder should remain committed and not alienated from the project. Methods of research Literature defining Primary data This date should be Qualitative and Quantative For companies dealing with employees sensitive personal information for payroll purposes, whether internally or through a third party, it is essential to ensure the right processes and procedures are in place to safeguard the data. See appendix 4 Literature defining Secondary data Secondary data is the data that have been already collected by and readily available from other sources. Such data are cheaper and more quickly obtainable than the primary data and may be available when primary data cannot be obtained at all. The credibility of the method and data must be accessed these factors have a direct influence on the accuracy of the data. The data collected for this research paper is (The International Journal of Human Resource Management, Vol. 24, No. 4, February 2013, 704-720). (Payroll and HR outsourcing, I.J.Maise march 2001). (Payroll Outsourcing: A New Paradigm. Princy Thomas and P K Thomas) CIPD factsheet on HR outsourcing 2016) This is referenced at the bottom of the report Meetings with the payroll administrator and the project leader and stakeholders are to be held to discuss the current situation and any issues or ideas for improvement. These meetings are important to establish different perspectives and build commitment to the project. Within these meetings, the researcher can interview the relevant people for their input on the project, this making qualative data. Benchmarking similar size companies outsourcing payroll would also be benefitable. The researcher should investigate the benefits following the implementation of outsourcing payroll before during and after. The researcher should seek advice from providers for insight into current trends available updates and support with reports. All information obtained should be equal and fair to make a fair comparison. Information on Return on investment should also be carried out. If the company chooses to outsource / bring in house this information is extremely important for signing off the project and setting scoring matrix for use when having structured interviews with the providers. Present Findings Different stakeholders will benefit from data being presented in different ways. Directors need detailed reports with a full breakdown on the project including costs and anticipated outcomes. The business case report should be presented as follows Executive summary The key reasons for doing the project The current service provision The key future requirements A summary of the full list of options A summary of the options selection procedure and the options chosen for detailed examination A summary of the comparative findings and justification for the preferred option Highlights of the Implementation Plan A statement to seek approval. Analysis of requirements. The Strategic Overview and Context-Provide an overview of the service or project, including strategic aims, policies and outcomes. Project Objectives-State the policy objectives that the project is required to meet. The Current Service Provision-Analyse the status and the issues with the current service. Options selection and evaluation Evaluation Criteria-State criteria for evaluating the benefits of the various options. Define these criteria in advance of identifying the options to avoid undue influence of the options. Identifying Available Options-State the available options and describe how the various options were identified, what methodology was used and why some options were discarded early (if any). Initial Evaluation and Consolidation-Explain how the shortlisted options were chosen and what options were shortlisted. Detailed Options Analysis-Provide an overview of the evaluation methodology. Benefits Evaluation-Quantitative as well as qualitative benefits for each option should be considered. Cost Evaluation-Discuss the various costing elements that were evaluated. Details regarding the assumptions used and the outcome of the evaluation should be presented. Cost elements typically include the following: Non-recurrent Costs-Describe the non-recurrent costs (or one off cost to establish the option) elements, including the transition cost, and the basis for deriving these costs. Recurrent Costs-Provide a description of costs that will be incurred throughout the life of the project. These costs may either be fixed or variable. Opportunity Cost- Opportunity cost is the cost of the next best foregone alternative to deliver a given option. Whole of Life Costs-Describe and include costs that will be incurred over the life of the project to ensure that the assets originally procured can continue to be delivered to a level of service that provides the required outcomes. The whole of life costs may include activities such as replacement of assets, refurbishing or upgrading specific asset elements. Strengths and Weaknesses Evaluation-Discuss the strengths and weaknesses of the options considered. Risk Analysis-Describe the process used for risk identification, risk quantification as well as key observations from this aspect. Detail any findings in a risk register. Sensitivity Analysis-Discuss the findings of any sensitivity analysis carried out to determine how sensitive the outcome of the analysis is to variations in the assumptions. Implementation planning Describe how the chosen option will be delivered and rolled out and the various issues that must be considered. Project Structure and Governance-Detail how the project will be managed and governed. Governance-Describe the chosen governance structure for the project, include information on individuals or positions that are already identified. Project Management-Describe the project management methodologies that will be used in delivering the project, including where available, a high level description of the organisational structure (could be graphical). Implementation Detail-Detail the programme and transition arrangements. Implementation Timing-Include a high-level implementation programme. This could cover single-stage or multi-stage delivery of the project. Present as a Gantt chart. see appendix 8 Transition Planning-Describe the activities and temporary arrangements required during the transitional phase. Constraints, Assumptions, Sourcing and Funding Requirements-Document identified constraints and the major assumptions made which affect the implementation. Sourcing and Procurement Strategy-Describe the chosen sourcing models with reasons why they were chosen and how goods and services will be procured and tracked. Funding Requirements-Describe what funding requirements are required, the timing, source and application/approval arrangements of the funds. Approach to Manage Risk, Communications and Resources Risk Management-Describe the risk management plan with detailed responsibilities and actions. Communications Strategy-Describe the required communications strategy together with what to communicate, to whom and when. Staff Resources-Detail what are the key issues, particularly from a human resources management point of view. This could include both staffing requirements for the project together with any impact caused by the project such as staff re-deployment or reductions/increases. Technical Considerations Describe any technical considerations, which could range from ICT requirements to general or specific engineering requirements. Regulatory Impact Assessment / Business Impact Assessment-Any impact on any regulatory bodies or regulated or third party businesses which could be adversely or positively affected by the introduction of the project should be included. Legislative Considerations-Detail any legislative aspects to the project that could require legislative changes or issue of new guidelines/codes of practice. The Post Implementation Review Process Explain how and when reviews will be carried out to check that the expected benefits have been realised and delivered. Also, describe how to track the benefits and report on them versus the original analysis. Within a company, Payroll is the main area outsourced per Statistics see appendix 5 Large competition and challenging environment has forced companies to focus more on added value and revenue generating core business activities rather than the routine of regular HR practices i.e. payroll most companies outsource payroll for various reasons according including reducing coat and controlling them. according to (Princy Thomas and P K Thomas). According to a study conducted in the US by PMRs payroll outsourcing satisfaction survey, it was found that out of the 215 respondent companies, 119 companies outsource payroll processing to a third party for activities such as tax filing, human resources, time and attendance, benefits administration, workers compensation administration and unemployment compensation administration (PMR, 2003) (appendix 6) Large competition and challenging environment has forced companies to focus more on added value and revenue generating core business activities rather than the routine of regular HR practices i.e. payroll most companies outsource payroll for various reasons according including reducing coat and controlling them. according to (Princy Thomas and P K Thomas). Benchmarking As per the office of national statistic, the government outsource the payroll The following information has been provided in relation to Payroll; We use the Logica payroll system, provided by CGI IT UK Limited. At the last count, in January 2017, there were 3,967 employees supported on the above system. The contract value when last purchased was  £840,000. The contract renewal date is 31/05/2022 We do not provide individual employee contact names to preserve Commercial confidentiality. Please contact us at [emailprotected] Not applicable 16th Feb 2016 Its official. New Research on the outsourcing market 2016-2020 has revealed that payroll outsourcing is the fastest-growing segment of the global human resource outsourcing (HRO) market. The report from Infiniti Research see appendix 5 indicates that organisations are rapidly adopting payroll services to achieve cost reduction. The in-depth market analysis used inputs from industry experts and covers the market landscape and its growth prospects over the coming years, and findings revealed a growth in either an outsourced single process or the entire payroll service to enhance the existing function. Managing payroll in-house involves high costs. The research revealed that organisations that maintain an in-house team for tasks such as payroll, time and attendance, workforce administration, and benefits administration spend 20% more than organisations that outsource the same functions.(Global payroll outsourcing market 2016-2020   2016 by   Infiniti Research) Employee Confidentiality and Ethics Mellewigt et al. (2007) explained the importance of trust and its influence on outsourcing relationship. Protection of payroll information is very crucial. Strict internal control measures should be in place to prevent payroll confidentiality breaches, as it will have disastrous effects on any organization. The business case reports accurately the information and informs how the company will function weather in house payroll or outsourced payroll. The information should provide consistent information to all audiences. The strategy to support the business objectives need to be highlighted along with the direct cost of savings benefit. Indirect benefits are often intangible this must be explained in the report, with the relevant case studies and reports to add credibility. I.e. payroll errors have an impact on the trust and morale of the employee by being under/ overpaid this can lead employees feeling less engaged and less motivated along with feeling undervalued. It can have an impact on the payroll administrator by increasing the pressure of mistrust. Employees would benefit by receiving information in an informal way by having a presentation with their managers who would also distribute the newsletter with the information. The newsletter would contain the relevant information which effects the individual. The project manager would also be present at the presentation so as the employees can ask questions without feeling intimidated. The Report for the finance team would consist of figures for cashflow purposes. The information would outline the initial costs, terms of payment, operating expenses, return on investment and budget. The information is to conduct an affordability assessment and prepare for budget and cashflow forecasts. Payroll outsourcing is the fastest-growing segment of the global human resource outsourcing (HRO) market. Organizations are rapidly adopting payroll services to achieve cost reduction. They either outsource a single process or the entire services to enhance the existing function. Managing payroll in-house involves high costs. Organizations that maintain an in-house team for tasks such as payroll, time and attendance, workforce administration, and benefits administration spend 20% more than organizations that outsource the same functions.The majority of payroll outsourcing functions are related to finance and accounting (FA), human capital management (HCM), and shared service centers. The HR department uses outsourcing services more commonly than any other departments. Technavios analysts forecast the global payroll outsourcing market to grow at a CAGR of 4.4% during the period 2016-2020.Payroll outsourcing is the fastest-growing segment of the global human resource outsourcing (HRO) market. Organizations are rapidly adopting payroll services to achieve cost reduction. They either outsource a single process or the entire services to enhance the existing function. Managing payroll in-house involves high costs. Organizations that maintain an in-house team for tasks such as payroll, time and attendance, workforce administration, and benefits administration spend 20% more than organizations that outsource the same functions.The majority of payroll outsourcing functions are related to finance and accounting (FA), human capital management (HCM), and shared service centers. The HR department uses outsourcing services more commonly than any other departments. Technavios analysts forecast the global payroll outsourcing market to grow at a CAGR of 4.4% during the period 2016-2020. Payroll outsourcing is the fastest-growing segment of the global human resource outsourcing (HRO) market. Organizations are rapidly adopting payroll services to achieve cost reduction. They either outsource a single process or the entire services to enhance the existing function. Managing payroll in-house involves high costs. Organizations that maintain an in-house team for tasks such as payroll, time and attendance, workforce administration, and benefits administration spend 20% more than organizations that outsource the same functions.The majority of payroll outsourcing functions are related to finance and accounting (FA), human capital management (HCM), and shared service centers. The HR department uses outsourcing services more commonly than any other departments. Technavios analysts forecast the global payroll outsourcing market to grow at a CAGR of 4.4% during the period 2016-2020.Payroll outsourcing is the fastest-growing segment of the global human resource outsourcing (HRO) market. Organizations are rapidly adopting payroll services to achieve cost reduction. They either outsource a single process or the entire services to enhance the existing function. Managing payroll in-house involves high costs. Organizations that maintain an in-house team for tasks such as payroll, time and attendance, workforce administration, and benefits administration spend 20% more than organizations that outsource the same functions.The majority of payroll outsourcing functions are related to finance and accounting (FA), human capital management (HCM), and shared service centers. The HR department uses outsourcing services more commonly than any other departments. Technavios analysts forecast the global payroll outsourcing market to grow at a CAGR of 4.4% during the period 2016-2020. Payroll outsourcing is the fastest-growing segment of the global human resource outsourcing (HRO) market. Organizations are rapidly adopting payroll services to achieve cost reduction. They either outsource a single process or the entire services to enhance the existing function. Managing payroll in-house involves high costs. Organizations that maintain an in-house team for tasks such as payroll, time and attendance, workforce administration, and benefits administration spend 20% more than organizations that outsource the same functions.The majority of payroll outsourcing functions are related to finance and accounting (FA), human capital management (HCM), and shared service centers. The HR department uses outsourcing services more commonly than any other departments. Technavios analysts forecast the global payroll outsourcing market to grow at a CAGR of 4.4% during the period 2016-2020.The evaluation of the contribution to the study. The HR Function has been trying to reposition itself, the aim is to encourage the function to be more strategic and have less administration tasks and to be more of a business support function and a facilitator of change rather than a guardian of the traditional function of employee welfare. HR are becoming high profile contributors at a strategic level they are well intergraded with the business and demonstrating they are adding value. Although extensive research ha

Tuesday, August 20, 2019

1,2,4-Oxadiazole Moiety Molecules Synthesis for Cancer

1,2,4-Oxadiazole Moiety Molecules Synthesis for Cancer 2.4. Synthesis of 3-(4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorophenyl)-5-substituted-1,2,4-oxadiazole derivatives for their MTT assay using MCF-7 breast cancer cell line and degradation of DNA in EAT cells 2.4.1. INTRODUCTION In the biological and pharmacological importance, heterocycles plays a significance role. Oxadiazole molecules show biologically activity includes angiogenesis inhibitor [246] and also HIV inhibitor [247], tyrosine kinase inhibition [45], histamine H3 antagonism [48], muscarinic agonism [49], potent histamine H2 receptor antagonists [50, 51], muscarinic receptor antagonists [53, 54], interleukin-8 (IL-8) receptor antagonists [65], cytotoxic activities [68], monoamine oxidase inhibition [66], potent therapeutic agents for prostate cancer [72], anticonvulsant activity [67], tumor-selective and apoptosis-inducing agents [70, 71], antitumor [4f] and apoptosis-inducing anticancer agents [73, 74]. Breast cancer is a most terrifying disease in which cells in breast tissue grow and divide without normal control. This type of growth of cells without control forms a lump called tumor. In breast cancer, tumors are called benign or malignant. Malignant tumors will grow by eating food. They get the food by forming new blood vessels in a process called angiogenesis. These blood vessels are the main reason to promote the growth of the tumors. After this tumor growing it will spread to nearby tissue, which is called as invasion. The breakage of main tumor cells will spread into other parts of the body and it will lead to metastatic breast cancer. This happens through blood stream or lymphatic system and this process is called metastasis. The main disadvantage of the malignant breast cancer is dividing and grows out of control which leads to form number of new tumors. If those new tumors are in other parts of the body, then also we call those as breast cancer. Especially in women, breast cancer leading to the cause of cancer related death. In developing and developed countries, breast cancer is the second most common malignancy type diagnosed disease in women. In India breast cancer is the most discussing problem in the current health problem (248). By the survey conceded by the Indian Council of Medical Research (ICMR), the percentage of breast cancer patients has been nearly doubled. In the past few years nearly one lakh new patients are being detected from 1985 to 2001 (249, 250). It has been estimated that the breast cancer in 2004 is nearly 90,273 and they predicted that in 2015 the patient’s number may be nearly 1, 12,680 (251). Due to the damage in DNA, normal cells will become cancer cells. DNA is present in every cell and it directs to all its actions. When DNA gets damaged in normal cells, the cell either repairs the damage or it dies. But in the cancer cells, damaged DNA is not repaired. The damaged cell undergoes splitting. As a result cell goes on making new cells that the body doesn’t need and those cells have same damaged DNA as the first cells does. This conjecture the design and synthesis of new anticancer drugs, and drug combination and treatment modalities is still the need for effective treatment of breast cancer patients [252]. 1,2,4-Oxadiazole moiety molecules show signs of vide variety of biological activities [40, 253-255]. In connection to the above studies, our molecules are subjected to the angiogenesis using MCF-7 breast cancer cell lines and degradation of DNA studies using in EAT cells. 2.4.2. MATERIALS Melting points were recorded (uncorrected) on a Buchi Melting Point B-545 instrument. Infrared (IR) spectra were recorded using a Jasco FTIR-4100 series. All reagents and solvents used were commercially procured and used as received. 1H-NMR spectra’s were recorded on Shimadzu AMX-400-Bruker with 400 MHz with TMS as internal standard. The 13C NMR spectra were examined on a Bruker DPX-400 at 100.6 MHz. The mass spectra were recorded on a JEOL JMS-AX505HA mass spectrometer. 2.4.3. EXPERIMENTAL 2.4.3.1. Chemistry General procedure for synthesis of (Z)-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluoro-N-hydroxybenzimidamide (2). A solution of hydroxylamine hydrochloride (1.529 g, 22.004 mmol) (2.5eq) and sodium carbonate (1.492 g, 14.082 mmol) (1.6eq) was taken in a round bottom flask. Stir for 10min to dissolve completely, then to this mixture 4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorobenzonitrile (1) (2.0 g, 8.801 mmol) (1.0 eq) is dissolved with ethanol was added. Then the mixture is heated to 60 0C about 5-6 hr. After that the steps forward of the reaction fusion was examined by the thin layer chromatography (TLC). After reaction completion, the solvent and the product was separated in vacuum pump under reduced pressure. Then the product was poured to water and extracted with ethyl ethanoate. The organic layer was washed 2-3 times with distilled water. The organic layer was washed 2-3 times with distilled water. The extracted ethyl ethanoate layer was dried over sodium sulphate (anhydrous) and the solvent was evaporated to get (Z)-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluoro-N-hyd roxybenzimidamide (2). 2.4.3.2. Synthesis of 3-(4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorophenyl)-5-substituted-1,2,4-oxadiazole 4(a-f) derivatives. (Z)-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluoro-N-hydroxybenzimidamide (2) (1.0 eq) is dissolved in dry dichloromethane and cooled to 0-5 0C in ice bath. Then N,N-diisopropylethylamine (1.1 eq) was added to cold reaction mixture and stirred for 10 minutes, then different aromatic acid chlorides (3a-e) (1 eq) were added. The reaction mixture was allowed to room temperature under stirring for 5-6 hr. After that the steps forward of the reaction fusion was examined by the thin layer chromatography (TLC). After reaction completion, the solvent and the product was separated in vacuum pump under reduced pressure. Then the product was poured to water and extracted with ethyl ethanoate. The organic layer was washed 2-3 times with distilled water. The organic layer was washed 2-3 times with distilled water. The extracted ethyl ethanoate layer was dried over sodium sulphate (anhydrous) and the product was purified with the help of column chromatography over silica gel (60-120 mesh) using hexane and ethyl acetate (1:1). Scheme 1. Reagents and conditions: (i) Sodium carbonate, water, ethanol, 60 0C, 6 h; (ii) dichloromethane, N,N-diisopropylethylamine, 0-5 0C, 6 h; 3(a-e) Where 3a = 4-chloro benzoyl chloride; 3b = 4-Fluoro benzoyl chloride; 3c = 4-(trifluoromethyl)benzoyl chloride; 3d = 4-Fluoro-3-Nitrobenzoyl chloride; 3e = 4-EthylPhenylbenzoyl chloride. 2.4.3.2.1. Synthesis of 5-(4-chlorophenyl)-3-(4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorophenyl)-1,2,4-oxadiazole (4a) Pale yellow color from (Z)-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluoro-N-hydroxybenzimidamide (2) (0.1 g, 0.384 mmol), 4-chlorobenzoylchloride (3a) (0.067 g, 0.384 mmol) and N,N-diisopropylethylamine (0.049 g, 0.461 mmol). 1H NMR (400 MHz, CDCl3): 8.32 (d, 1H, Ar-H), 7.75 (dd, 2H, Ar-H), 7.70, (d, 1H, imid-H), 7.55 (d, 1H, Ar-H), 7.50 (dd, 2H, Ar-H), 7.35 (d, 1H, imid-H), 7.30 (d, 1H, Ar-H), 5.05 (d, 1H, pyrrole-H), 2.56-2.30 (d, 4H, pyrrole-H); MS (ESI) m/z: 381.081 (100.0%), Anal. calcd. for C20H14ClFN4O (in %): C- 63.08, H- 3.71, N- 14.71. 2.4.3.2.2. Synthesis of 3-(4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorophenyl)-5-(4-fluorophenyl)-1,2,4-oxadiazole (4b) Orange color from (Z)-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluoro-N-hydroxybenzimidamide (2) (0.1 g, 0.384 mmol), 4-Fluoro benzoyl chloride (3b) (0.060 g, 0.384 mmol)and N,N-diisopropylethylamine (0.049 g, 0.461 mmol). 1H NMR (400 MHz, CDCl3): 8.31 (d, 1H, Ar-H), 7.30 (dd, 2H, Ar-H), 7.72, (d, 1H, imid-H), 7.56 (d, 1H, Ar-H), 7.34 (d, 1H, imid-H), 7.31 (d, 1H, Ar-H), 7.29 (dd, 2H, Ar-H), 5.02 (d, 1H, pyrrole-H), 2.58-2.31 (d, 4H, pyrrole-H); MS (ESI) m/z: 365.114 (100.0%), Anal. calcd. for C20H14F2N4O (in %): C- 65.93, H- 3.87, N- 15.38. 2.4.3.2.3. Synthesis of 3-(4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorophenyl)-5-(4-(trifluoromethyl)phenyl)-1,2,4-oxadiazole (4c) Dark brown color from (Z)-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluoro-N-hydroxybenzimidamide (2) (0.1 g, 0.384 mmol), 4-(trifluoromethyl)benzoyl chloride (3c) (0.080 g, 0.384 mmol) and N,N-diisopropylethylamine (0.049 g, 0.461 mmol). 1H NMR (400 MHz, CDCl3): 8.33 (d, 1H, Ar-H), 8.10 (dd, 2H, Ar-H), 7.74 (d, 1H, imid-H), 7.70 (dd, 2H, Ar-H), 7.58 (d, 1H, Ar-H), 7.37 (d, 1H, imid-H), 7.33 (d, 1H, Ar-H), 5.06 (d, 1H, pyrrole-H), 2.59-2.29 (d, 4H, pyrrole-H); MS (ESI) m/z: 415.110 (100.0%), Anal. calcd. for C21H14F4N4O (in %): C- 60.87, H- 3.41, N- 13.52. 2.4.3.2.4. Synthesis of 3-(4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorophenyl)-5-(4-fluoro-3-nitrophenyl)-1,2,4-oxadiazole (4d) Pale yellow color from (Z)-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluoro-N-hydroxybenzimidamide (2) (0.1 g, 0.384 mmol), 4-Fluoro-3-Nitrobenzoyl chloride (3d) (0.078 g, 0.384 mmol)and N,N-diisopropylethylamine (0.049 g, 0.461 mmol). 1H NMR (400 MHz, CDCl3): 8.71 (d, 1H, Ar-H), 8.65 (d, 1H, Ar-H), 8.34 (d, 1H, Ar-H), 7.74 (d, 1H, imid-H), 7.61 (dd, 1H, Ar-H), 7.58 (d, 1H, Ar-H), 7.37 (d, 1H, imid-H), 7.33 (d, 1H, Ar-H), 5.06 (d, 1H, pyrrole-H), 2.59-2.29 (d, 4H, pyrrole-H); MS (ESI) m/z: 410.099 (100.0%), Anal. calcd. for C20H13F2N5O3 (in %): C- 58.68, H- 3.20, N- 13.52. 2.4.3.2.5. Synthesis of 3-(4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorophenyl)-5-(5-ethyl-[1,1-biphenyl]-2-yl)-1,2,4-oxadiazole (4e). White color from (Z)-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluoro-N-hydroxybenzimidamide (2) (0.1 g, 0.384 mmol), 4-EthylPhenylbenzoyl chloride (3e) (0.094 g, 0.384 mmol) and N,N-diisopropylethylamine (0.049 g, 0.461 mmol). 1H NMR (400 MHz, CDCl3): 8.31 (d, 1H, Ar-H), 7.95 (d, 1H, Ar-H), 7.80 (dd, 2H, Ar-H), 7.75 (d, 1H, Ar-H), 7.72, (d, 1H, imid-H), 7.53 (dd, 2H, Ar-H), 7.56 (d, 1H, Ar-H), 7.45 (d, 1H, Ar-H), 7.34 (d, 1H, imid-H), 7.30 (d, 1H, Ar-H), 7.31 (d, 1H, Ar-H), 5.03 (d, 1H, pyrrole-H), 2.65 (q, 2H, -CH2), 2.58-2.31 (d, 4H, pyrrole-H), 1.27 (t, 3H, -CH3),; MS (ESI) m/z: 451.186 (100.0%), Anal. calcd. for C28H23FN4O (in %): C- 74.65, H- 5.15, N- 12.44. 2.4.4. Biology 2.4.4.1. Culture of MCF-7 cells: MCF-7 cells were cultured with minor modification in Minimal Essential medium (Invitrogen) supplemented with 10% fetal bovine serum, 100units/ml penicillin-G, 100  µg/ml streptomycin and 1% sodium bicarbonate (Invitrogen). MCF-7 cells were obtained from Cell repository unit of National Center for Cell Sciences (NCCS), Pune, India. All cell lines were maintained at 37 °C in a humidified atmosphere with 5% CO2 [256]. 2.4.4.2. Culture of EAT cells: Animals, in vivo tumor generation and imidazole derivatives treatment Six to eight weeks old female mice were acclimated for one week while caged in-group of five. Mice were housed and fed a diet of animal chow and water ad libitum throughout the experiment. All the experiments were approved by the institutional animal care and use committee of the University of Mysore, Mysore, India. Ehrlich Ascites Tumor (EAT) cells (5Ãâ€"106 cells/mouse) were injected intraperitoneally. These cells grow in mouse peritoneum forming an ascites tumor with massive abdominal swelling. The animals showed a dramatic increase in body weight over the growth period and the animals succumbed to the tumor burden 14–16 days after implantation. 2.4.4.2.1. Isolation of EAT cells from mice peritoneal cavity and compound treatment: From the peritoneal cavity of tumor-bearing mice the EAT cells were isolated (control and treated). 2-3 mm of sterile PBS was injected in to the peritoneal cavity of the mice and the peritoneal fluid containing tumor cells withdrawn, collect in sterile petri dishes and incubated at 370C for 2 h. The cells of macrophage linage adhered to the bottom of Petri dishes. The non-adherent population was aspirated out gently and washed repeatedly with PBS. Moreover, viability of these cells was assessed and was found to be >95% by trypan blue dye exclusion. The viable EAT cells were processed for further experiments. The EAT cells (5 x 106) were treated with or without compounds of 3-(4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorophenyl)-5-substituted-1,2,4-oxadiazole series 4(a-e) and incubated at 370 C for different time interval or for known period of time. After the incubation period the cells w ere used for the further analysis [258]. 2.4.4.2.2. Cell count by Trypan blue dye exclusion assay. EAT cells were treated with different concentrations of 3-(4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorophenyl)-5-substituted-1,2,4-oxadiazole compounds 4(a-e) at various time periods (0–4 h). Cell viability was assessed by mixing aliquots of cell suspension with 0.4% trypan blue and counted using heamocytometer. Cells that picked up the dye were considered to be dead [259(a)]. 2.4.5. Result and Discussion 2.4.5.1. Chemistry Synthesis of the key intermediate (Z)-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluoro-N-hydroxybenzimidamide (2) is outlined in Scheme 1. Briefly, hydroxylamine hydrochloride and sodium carbonate was taken in water and stirred. 4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorobenzonitrile (1) was dissolved in ethanol and added to the reaction mixture. The presence of –NH2 and =N-OH proton peaks NMR spectra indicates the formation of (Z)-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluoro-N-hydroxybenzimidamide (2). The key intermediate compound (2) was taken in dry dichloromethane and cooled to 0-5 0C, and N,N-diisopropylethylamine was added. Stirred for 10 min, then different aromatic acid chlorides 3(a-e) was added drop by drop. The reaction mixture was allowed to room temperature under stirring for 5-6 h and after that the steps forward of the reaction fusion was examined by the thin layer chromatography (TLC). After reaction completion, the solvent and th e product was separated in vacuum pump under reduced pressure. Then the product was poured to water and extracted with ethyl ethanoate. The organic layer was washed 2-3 times with distilled water to get target 3-(4-(3-(1H-imidazol-5-yl)propyl)-3-fluorophenyl)-5-substituted-1,2,4-oxadiazole 4(a-e). Upon completion crude products 4(a-e) were obtained with a good yield of 81–93% and which the product was purified with the help of column chromatography over silica gel (60-120 mesh) using hexane and ethyl acetate (1:1). The absence of –CO proton peak in synthesized derivatives in 1H spectra confirmed the identity of the products. The details of chemical structures, physical data and purity of compounds are given in Table 1. Compound R1 Yield MP (oC) Purity 4a 90 277 90 4b 85 100 93 4c 81 110 89 4d 82 142 92 4e 79 95 81 Table 1. Chemical structures, physical data and purity of compounds 4(a–e) 2.4.5.2. Biology 2.4.5.2.1. MTT assay: The MTT assay was performed according to the protocol previously reported [257]. MCF-7 cells were plated at a density of 1 X 105 cells in 96-well plates. (Subsequently, the 3-(4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorophenyl)-5-substituted-1,2,4-oxadiazole series 4(a-e) were assayed using concentrations from 0.05 to 0.5 mM). After 24 h of incubation, 10  µL of 5% 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) (Sigma Aldrich) (0.05 mg/mL) were added to the culture medium. After 4 h at 370C the culture medium was removed and 200  µL of DMSO were added to dissolve the salts of formazan. The absorbance was measured with a 96-wells plate spectrophotometer at 570 nm. The experiments were independently performed three times and each experiment contained triple replicates. Control samples containing a complete culture medium devoid of cells or control cells with 0.1% DMSO were also included in each experiment. Figure 1. The MTT assay of compounds 4(a-e) in MCF-7 breast cancer cell lines. Sl.No. Name of the compound IC50 Value 1 Cisplatin 10ÃŽ ¼g 2 4a 100ug 3 4b 200ug 4 4c 100ug 5 4d 800ug 6 4e 200ug Table 2. Compounds 4(a-e) and their IC50 value ( µg/ml) on MCF-7 breast cancer cell lines. 2.4.5.3. DNA fragmentation assay: EAT cells were collected from mice treated with or without 3-(4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorophenyl)-5-substituted-1,2,4-oxadiazole series 4(a-e). Thein vivo and DNA was isolated using the phenol–chloroform method. In brief, cells were lysed in a buffer containing 50mM Tris–HCl, pH 8.0, and 0.5% SDS, and incubated for 30min at 37 °C. The cell lysate was subjected to 8M potassium acetate precipitation and left for 1h at 4 °C. The supernatant was subjected to phenol/chloroform/isoamyl alcohol (25:24:1) extraction and once to chloroform extraction. DNA was precipitated by adding 1:2 volumes of ice-cold ethanol. The precipitated DNA was dissolved in 50ÃŽ ¼L TE buffer (pH 8.0). The DNA was digested with 20ÃŽ ¼g/mL RNase at 37 °C for 1h. The DNA was quantitated and equal concentration of DNA (25ÃŽ ¼g) was resolved on 1.5% agarose gel, viewed under UV light, and documented using BIORAD gel documentation system Figure 2 [259(b)]. Figure 2. The DNA degradation of compounds 4(a-e) in Ehrlich Ascites Tumor (EAT) cells. Conclusion: A series of 3-(4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorophenyl)-5-substituted-1,2,4-oxadiazoles 4(a-e) has been synthesized by using simple synthetic procedures and were screened for their MTT assay using MCF-7 breast cancer cell line and degradation of DNA in Ehrlich Ascites Tumor (EAT) cells activity. All the final compounds exhibited good in all the in-vitro activity.

Monday, August 19, 2019

Western Expansion Essay -- United States History Historical Essays

The Westward Expansion Introduction The Westward Expansion has often been regarded as the central theme of American history, down to the end of the19th century and as the main factor in the shaping of American history. As Frederick Jackson Turner says, the greatest force or influence in shaping American democracy and society had been that there was so much free land in America and this profoundly affected American society. Motives After the revolution, the winning of independence opened up the Western country and was hence followed by a steady flow of settlers to the Mississippi valley. By 1840, 10 new western states had been added to the Federal union. The frontier line ran through Iowa, Missouri and Arkansas on the western side of the river. All parts of the valley except Wisconsin and Minnesota were well populated. Thus a whole new section had been colonized with lasting effects on the American institutions, ideals and ways of living. The far west was the land of high mountains, deserts, strange rock formations, br illiant colors and immense distance. Fur trade with Europe had now become a lucrative business and the fur traders became the pathfinders for the settlers. Migration was now possible by the discovery of paths over which ox-driven carts could be driven through seeking mountains and across the western desert. People wanted to move away from the overcrowded cities and this led to the migration into the uninhabited lands. Increased transportation like roads, railroads and canals and their construction created a demand for cheap labor making it easier for people to get jobs now, in contrast with the cities where there was unemployment. The pioneer movement for 70 years after the revolution roughly represented the form of 3 parallel streams, flowing westwards from New England, Virginia and South Carolina. The first pioneer groups tended to move directly westward. Thus the new Englanders migrated into western New York and along the shores of the great lakes, Virginians into Kentucky and th en into Missouri and the South Carolinians and Georgians into the gulf territories. Throughout the settlement of the Mississippi valley, most pioneers did not travel long distances and as a territory had been occupied, families would move into the adjacent one. There were boom periods of great activity, during which million acres of land were sold, alternated ... ...or wider opportunities. Even the safety valve theory has an element of truth when applied to ambitious young men of the professional class who had a better chance of making it big much quicker in the West than in the East. Without the open frontier, moreover, there would have been a much larger migration of young people from the farms to the cities; thus the frontier helped indirectly to check the exploitation of the working class by preventing it from expanding too rapidly. The Westward Expansion also weakened state and regional loyalties and promoted national unity due to its inherent mobility. Most westerners thought of themselves primarily as Americans, and wanted strong national government with broad powers for developing transportation and promoting the general welfare. The most significant feature of the Westward Expansion was that the pioneers took with them the essential institutions of their civilization. Thus we must look upon the Westward Expansion as one of the facto rs in the shaping of the American civilization but not the only one. AKSHARA PRADHAN Roll No. 385 Tute. Grp.- Tuesday, 1st Pd. Bibliography the history of the united states of america -H.B.Parkes