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Please see an attachment for details Image transcription textEXERCISE 14—15 Internal Rate of Return and Net Present Value LO14—2, LO14—3 Henrie’s Drapery Service isinvestigating the purchase of a new machine for cleaning and blocking drapes. The machine would cost$137,320, including freight and installation. Henrie’s estimated the new machine would increase th… Show more… Show more   Accounting Business Managerial Accounting ACCTG 104 Share QuestionEmailCopy link

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Question Answered step-by-step IntroductionWhen most people Given that no two individuals look exactly alike (apart from identical twins) it will come as no surprise that this is reflected in our DNA. What is surprising is the amount of variation between us. Looking at any one human genome, compared with the reference sequence, we would find approximately 3 million SNPs, and approximately 2000 structural variants. The genomes of any two unrelated individuals will differ in approximately 0.5% of their DNA (approximately 15 million bp), and most of this variation can be attributed to CNVs and large deletions. Although much of the variation in our genome lies within the non-coding DNA, we now know that, on average, each individual has several hundred variants that are either known, or predicted, to be damaging to gene function, including roughly 85 variants that lead to truncated (incomplete) protein products. Furthermore, the total number of functional genes per human genome may vary by up to 10% between individuals as a consequence of CNVs, large deletions and loss-of-function variants. Faced with this enormous level of variation you might wonder, not why some individuals are affected by disease due to inherited 'mutations', but rather how any of us manage to remain relatively healthy! Clearly there is no requirement for all of our genes to be functional: for many genes only one working copy is required, and in other cases there appears to be a level of redundancy or plasticity built into the system. However it is becoming increasingly apparent that some of the variations in our genomes may lead to higher susceptibility to common diseases. Given that no two individuals look exactly alike (apart from identical twins) it will come as no surprise that this is reflected in our DNA. What is surprising is the amount of variation between us. Looking at any one human genome, compared with the reference sequence, we would find approximately 3 million SNPs, and approximately 2000 structural variants. The genomes of any two unrelated individuals will differ in approximately 0.5% of their DNA (approximately 15 million bp), and most of this variation can be attributed to CNVs and large deletions. Although much of the variation in our genome lies within the non-coding DNA, we now know that, on average, each individual has several hundred variants that are either known, or predicted, to be damaging to gene function, including roughly 85 variants that lead to truncated (incomplete) protein products. Furthermore, the total number of functional genes per human genome may vary by up to 10% between individuals as a consequence of CNVs, large deletions and loss-of-function variants. Faced with this enormous level of variation you might wonder, not why some individuals are affected by disease due to inherited 'mutations', but rather how any of us manage to remain relatively healthy! Clearly there is no requirement for all of our genes to be functional: for many genes only one working copy is required, and in other cases there appears to be a level of redundancy or plasticity built into the system. However it is becoming increasingly apparent that some of the variations in our genomes may lead to higher susceptibility to common diseases. Given that no two individuals look exactly alike (apart from identical twins) it will come as no surprise that this is reflected in our DNA. What is surprising is the amount of variation between us. Looking at any one human genome, compared with the reference sequence, we would find approximately 3 million SNPs, and approximately 2000 structural variants. The genomes of any two unrelated individuals will differ in approximately 0.5% of their DNA (approximately 15 million bp), and most of this variation can be attributed to CNVs and large deletions. Although much of the variation in our genome lies within the non-coding DNA, we now know that, on average, each individual has several hundred variants that are either known, or predicted, to be damaging to gene function, including roughly 85 variants that lead to truncated (incomplete) protein products. Furthermore, the total number of functional genes per human genome may vary by up to 10% between individuals as a consequence of CNVs, large deletions and loss-of-function variants. Faced with this enormous level of variation you might wonder, not why some individuals are affected by disease due to inherited 'mutations', but rather how any of us manage to remain relatively healthy! Clearly there is no requirement for all of our genes to be functional: for many genes only one working copy is required, and in other cases there appears to be a level of redundancy or plasticity built into the system. However it is becoming increasingly apparent that some of the variations in our genomes may lead to higher susceptibility to common diseases. Given that no two individuals look exactly alike (apart from identical twins) it will come as no surprise that this is reflected in our DNA. What is surprising is the amount of variation between us. Looking at any one human genome, compared with the reference sequence, we would find approximately 3 million SNPs, and approximately 2000 structural variants. The genomes of any two unrelated individuals will differ in approximately 0.5% of their DNA (approximately 15 million bp), and most of this variation can be attributed to CNVs and large deletions. Although much of the variation in our genome lies within the non-coding DNA, we now know that, on average, each individual has several hundred variants that are either known, or predicted, to be damaging to gene function, including roughly 85 variants that lead to truncated (incomplete) protein products. Furthermore, the total number of functional genes per human genome may vary by up to 10% between individuals as a consequence of CNVs, large deletions and loss-of-function variants. Faced with this enormous level of variation you might wonder, not why some individuals are affected by disease due to inherited 'mutations', but rather how any of us manage to remain relatively healthy! Clearly there is no requirement for all of our genes to be functional: for many genes only one working copy is required, and in other cases there appears to be a level of redundancy or plasticity built into the system. However it is becoming increasingly apparent that some of the variations in our genomes may lead to higher susceptibility to common diseases.consider the genetic basis of disease, they might think about the rare, single gene disorders, such as cystic fibrosis (CF), phenylketonuria or haemophilia, or perhaps even cancers with a clear heritable component (for example, inherited predisposition to breast cancer). However, although genetic disorders are individually rare, they account for approximately 80% of rare disorders, of which there are several thousand. The sheer number of rare disorders means that, collectively, approximately 1 in 17 individuals are affected by them. Moreover, our genetic constitution plays a role, to a greater or lesser extent, in all disease processes, including common disorders, as a consequence of the multitude of differences in our DNA. Some of these differences, alone or in combinations, might render an individual more susceptible to one disorder (for example, a type of cancer), but could render the same individual less susceptible to develop an unrelated disorder (for example, diabetes). The environment (including lifestyle) plays a significant role in many conditions (for example, diet and exercise in relation to diabetes), but our cellular and bodily responses to the environment may differ according to our DNA. The genetics of the immune system, with enormous variation across the population, determines our response to infection by pathogens. Furthermore, most cancers result from an accumulation of genetic changes that occur through the lifetime of an individual, which may be influenced by environmental factors. Clearly, understanding genetics and the genome as a whole and its variation in the human population, are integral to understanding disease processes and this understanding provides the foundation for curative therapies, beneficial treatments and preventative measures.With so many genetic disorders, it is impossible to include more than a few examples within this review, to illustrate the principles. For further information on specific conditions, there are a number of searchable internet resources that provide a wealth of reliable detail. These include Genetics Home Reference (https://ghr.nlm.nih.gov/), Gene Reviews (https://www.ncbi.nlm.nih.gov/books/NBK1116/), the 'Education' section from the National Human Genome Research Institute (https://www.genome.gov/education/) and Online Mendelian Inheritance in Man (https://www.omim.org/). In this review, an understanding and knowledge of basic principles and techniques in molecular biology, such as the structure of DNA and the PCR will be assumed, but explanations and animations of PCR (and some other processes) are available from the DNA Learning Center (https://www.dnalc.org/resources/). The focus here will be on human disease, although much of the research that defines our understanding comes from the study of animal models that share similar or related genes.The human genome and variationThe human genome and the human genome reference sequenceThe complete instructions for generating a human are encoded in the DNA present in our cells: the human genome, comprising roughly 3 billion bp of DNA. Scientists from across the world collaborated in the 'Human Genome Project' to generate the first DNA sequence of the entire human genome (published in 2001), with many additions and corrections made in the following years. Genome sequence information for humans and many other species is freely accessible through a number of portals, including the National Center for Biotechnology Information (NCBI; https://www.ncbi.nlm.nih.gov/) and Ensembl (http://www.ensembl.org/), which also provide a wealth of related information.The majority of our DNA is present within the nucleus as chromosomes (the nuclear DNA or nuclear genome), but there is also a small amount of DNA in the mitochondria (the mtDNA or mitochondrial genome). Most individuals possess 23 pairs of chromosomes (Figure 2), therefore much of the DNA content is present in two copies, one from our mother and one from our father.The human nuclear genome encodes roughly 20000 protein-coding genes, which typically consists of both protein-coding (exon) and non-coding (intron) sequences. Our genome also contains roughly 22000 genes that encode RNA molecules only; some of these RNAs form components of the translation machinery (rRNA, tRNA) but there are many more that perform various roles within the cell, including regulation of expression of other genes. In fact it is now believed that as much as 80% of our genome has biological activity that may influence structure and function. The human genome also contains over 14000 'pseudogenes'; these are imperfect copies of protein-coding genes that have lost the ability to code for protein. Although originally considered as evolutionary relics, there is now evidence that some may be involved in regulating their protein-coding relatives, and in fact dysregulation of pseudogene-encoded transcripts has been reported in cancer. Additionally, sequence similarity between a pseudogene and its normal counterpart may promote recombination events which inactivate the normal copy, as seen in some cases of perinatal lethal Gaucher disease. Furthermore, some pseudogenes have the potential to be harnessed in gene therapy to generate functional genes by gene editing approaches. The distribution of genes between chromosomes is not equal: chromosome 19 is particularly gene-dense, while the autosomes for which trisomy is viable (13, 18, 21) are relatively gene-poor (Table 1).Table 1DNA and gene content of human chromosomesChromosome Approximate length (bp) Protein-coding genes Non-protein coding genes Pseudogenes1  248956422  2047  1964  1233 2  242193529  1303  1605  1033 3  198295559  1075  1160  768 4  190214555  753  984  732 5  181538259  881  1200  710 6  170805979  1041  989  803 7  159345973  989  977  893 8  145138636  670  1041  629 9  138394717  778  786  678 10  133797422  728  880  568 11  135086622  1312  1053  815 12  133275309  1036  1197  627 13  114364328  321  586  378 14  107043718  820  857  519 15  101991189  613  986  513 16  90338345  867  1033  467 17  83257441  1185  1198  531 18  80373285  269  608  246 19  58617616  1474  895  514 20  64444167  543  594  250 21  46709983  231  403  183 22  50818468  492  513  332 X  156040895  843  640  872 Y  57227415  63  108  392 Mitochondrial  16569  13  24   Teaching the community to wash their hands after defecation, after cleaning a child's bottom, and before eating and preparing food. Caretakers of children should be taught using demonstrative techniques the safe disposal of children's faeces and about key behaviours and misconceptions about hygiene promotion activities. Representatives from all user groups should to be involved in planning, training, implementation, monitoring and evaluation of hygiene promotion. That involvement of all groups may facilitate information flow between humanitarian actors and the affected population so that misconceptions where identified, are addressed. In the early stages of a disaster the use of mass media for hygenie promotion may increase its impact on the targeted population. Information should be disseminated using different channels and by targeting different at-risk groups especially those who are illiterate, have communication difficulties and those who do not have access to traditionaldevices to accesss media such as radio or television or internet.The planning of hygiene promotion must be culturally appropriate and may offer useful opportunities for affected people to monitor their own hygiene improvements. The use of outreach workers or home visitors provides an interactive way to access large numbers of people. In a camp setting, there should be two hygiene promoters per 1,000 members of the affected population. For an effective hygenie promotion activity, all men, women and children of all ages should receive information regarding the priority hygiene items. A basic minimum hygiene items pack consists of water containers (buckets), bathing and laundry soaps, and menstrual hygiene materials. Every housing unit requires two 10-20 litre capacity water containers, one for transportation and one for storage. Soap for bathing (250 mg) and a laundry (200 mg) and additionaly acceptable menstrual hygenie materials for women should be distributed regulary every month. Members of the community should be trained regarding safe and effective use of hygenie items if these are unfamiliar.. Use and satisfaction with distributed hygenie material should be monitored regularly after distribution and necessary adjustments made after receiving feedback.[11]The affected population may need additional items which are not included in basic hygenie packets such as blankets etc. depending on environmental conditions. Also people with specific needs (e.g. incontinence or severe diarrhoea may require increased quantities of personal hygiene items such as soap). Those who are confined to bed may need additional items, such as bed pans. According to socio-cultural practices, hygenie packages may include tootbrushes, toothpaste, shampoo, razors, combs, nail clippers and diappers. To ensure timely distribution of the hygenie items the cooperation and agreement of the affected population is essential.[11] The components of the aid package should be vetted with community leaders and each item reviewed for need based on envorment and cultural acceptance prior to mass dissemination.Go to:3. Water Supply and Treatment of Drinking-Water in Emergency SituationsWater is essential for life, health and human dignity. In extreme situations having Access to clean water for meeting basic needs has a critical importance. Many times poor hygenie due to insufficient water or consumption of contaminated water is the main reason for spraed of infection. In a disaster, the main priority is to provide safe and equitable access to an adequate amount of water for drinking, cooking and personal and domestic hygiene even if it is of intermediate quality.[12] Therefore location of public water points should be planned sufficiently close to households to enable use of the minimum water requirement.Water consumption data should be also obtained directly from community sources or household surveys. Data collected using these methods will be more effective than the measurement of water pumped into the pipeline. According to Sphere Standarts, minimal water intake need for a victims survival is 2.5-3 /lt/day and varies with the climate and individual physiology. Total quantity should also include water for basic hygenie practices (2-6 litres per day) and basic cooking needs (3-6 litres per day) bringing the total requirement to 7.5-15 litres per day. This amount is >20 litres according UNHCR standards. (R2) The proximity and sustainability of sufficient quantity of water should be considered. When selecting water sources groundwater and/or gravity-flow supplies from springs are preferable, as they require less treatment and no pumping.[12]According to Sphere Standards accesibility to water should be limited to 8 hours/day in order to prevent overuse and misuse of the water sources. Approximate flow rates according to guidelines are as follows; 250 people per tap based on a flow of 7.5 litres/minute, 500 people per hand pump based on a flow of 17 litres/minute and 400 people per single-user open well based on a flow of 12.5 litres/minute. All community members should have equitable access to water points regardless of gender or ethnicity. Also, water distribution and pumping times should be planned in consultation with the users including women and minorities. The maximum distance from any household to the nearest water point should be 500 metres and maximum queueing time at a water source 30 minutes.[12]Go to:Water Quality and Emergency Treatment of Drinking Water• What are two potential solutions to improve the downtime? What are the average mean, frequency, and standard deviation of downtimes?   Health Science Science Nursing Share QuestionEmailCopy link Comments (0)
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