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Although the fit with the single-locus hypothesis is excellent pain management treatment plan template order anacin 525mg with amex, the five taster offspring in the nontaster matings are unexplained pain swallowing treatment buy anacin 525 mg overnight delivery. They could be due to misclassification of phenotype back pain treatment kolkata anacin 525mg without prescription, to misassigned parentage backbone pain treatment yoga purchase 525 mg anacin amex, or perhaps to alleles at other loci that influence tasting ability pain management with shingles generic anacin 525 mg overnight delivery. This observation supports the second hypothesis: Every person excretes the substance pain after lithotripsy treatment discount 525 mg anacin with amex, but not every person is able to smell it. Severe Mental Disorders Examples of both genetic and environmental effects on mental function are easily enumerated. Down syndrome and the fragile-X syndrome are major genetic causes of mental retardation (Section 7. Another inherited form of mental retardation is phenylketonuria, an inborn error of metabolism caused by an autosomal recessive gene at 12q24. The metabolic defect causes profound mental deficiency unless the dietary intake of phenylalanine is rigorously controlled. On the environmental side, severe mental impairment of genetically normal infants can result from prenatal infection with rubella virus (German measles), excessive exposure of the fetus to alcohol (fetal alcohol syndrome), insufficient oxygen or brain damage at Table 17. Shields, Schizophrenia: the Epigenetic Puzzle Cambridge, England: Cambridge University Press, 1982) birth, and many other factors. These examples illustrate that assignment of the primary cause of mental retardation to genetics or environment must be done on a case-by-case basis. As might be expected, in many instances, the precise cause is unas-signable, so it remains unclear what overall proportion of mental retardation is genetic in origin and what proportion is environmental. In view of its severity, the trait is remarkably common, affecting about 1 person in 100. The genetic contribution to the trait is seen in the high concordance (46 percent) in identical twins, in the high risk among children with two affected parents, and in the substantial risk among adopted children when their biological mother is affected. Indeed, regarding schizophrenia, adopted children resemble their biological parents more than their adoptive parents. The genetic risk factors for schizophrenia have not been identified, but it is clear that there are multiple genetic factors and that the relative importance of the genetic factors differs from one kindred to the next. Genetic mapping studies in families with schizophrenia have implicated genes at least in chromosomes 5q, 6p, and 22q. The environmental component is evidenced by the incomplete concordance of identical twins (when one twin is affected, there is a 46 percent chance that the other will also be affected) and by the increased risk in normal children adopted into families in which one partner later develops schizophrenia. Most psychiatric geneticists currently favor the view that genotype is an important predisposing factor toward schizophrenia but that environmental stress is an essential trigger for actual onset of the disease. Severe mental retardation, senile dementia (such as Alzheimer disease), and personality disorders (such as schizophrenia) lie well outside the range of normal intellectual function. Hence the relative importance of genetic and environmental Page 731 contributions to these conditions may not yield an accurate picture of behavioral differences among people. Among any random collection of people, there is enormous variation in personality, emotional traits, and intellectual abilities. How much of this variation can be attributed to genotypic differences among people and how much can be attributed to differences in their environments? This is the key issue in understanding how genes influence human behavioral traits. Genetics and Personality the possible role of hereditary factors in influencing human personality traits within the normal range of variation in personality is difficult to assess. If the genetic factors consist of more than a handful of genes, each with a relatively small effect, then the genetic factors are very difficult to detect, even using the methods outlined in Chapter 16 for genetic mapping of quantitative-trait loci. Even though the genes cannot be identified individually, it is nevertheless possible to estimate how important genetic factors are, in the aggregate, by separating the observed variance in the trait into a genetic variance component (estimating the importance of genetic factors in causing the total variance in phenotype) and an environmental component (estimating the importance of environmental factors in causing the total variance in phenotype). One overall measure of the importance of genetic factors in determining the variance of a trait is the broad-sense heritability, which is the ratio obtained by dividing the variance in phenotype attributable to differences in genotype by the total variance in phenotype from all causes together. The broad-sense heritability of personality traits has been estimated experimentally from studies of identical twins reared together and reared apart in comparison with fraternal twins and ordinary siblings reared together and reared apart. For each of five broad personality traits, the broad-sense heritability ranges from 30 percent to 50 percent (Figure 17. Each of these broad personality traits is expressed not in an all-or-none fashion but quantitatively. After examination by trained personnel, each person can be assigned a score on a continuous scale of measurement reflecting the degree to which the trait is expressed in the person. Agreeableness: a trait associated with friendliness, likeability, and pleasantness People who strongly express this trait are sympathetic, warm, kind, and good-natured, and they tend not to take advantage of others. The opposite end of the scale is associated with aggressiveness, pugnacity, coldness, and vindictiveness. People who score strongly negative for this trait are impulsive, careless, and undependable. At the other end of the scale are introverts, who tend to be reserved and withdrawn and to avoid attention. People at the opposite end of the scale are easy-going, emotionally stable, and not prone to high anxiety. People at the negative end of the openness scale are described as shallow or lacking in curiosity. A knowledge that the broad-sense heritability of each of these personality traits is from 30 percent to 50 percent tells us nothing about the number of genes that are Page 732 Figure 17. The broad-sense heritability equals the sum of the additive and nonadditive percentages. Because many of the genes affecting personality may have relatively small effects, they are likely to remain undetected in the usual types of pedigree studies for genetic mapping. Another approach to the identification of genes that influence personality and behavior is through candidate genes. A candidate gene for a trait is a gene for which there is some a priori basis for suspecting that the gene may affect the trait. In human behavior genetics, for example, if a pharmacological agent is known to affect a personality trait, and the molecular target of the drug is known, then the gene that codes for the target molecule and any gene whose product interacts with the drug or with the target molecule are all candidate genes for affecting the personality trait. One example of the use of candidate genes in the study of human behavior genetics is in the identification of a naturally occurring genetic polymorphism that affects neuroticism and, in particular, the anxiety component of neuroticism. The neurotransmitter substance serotonin (5-hydroxytryptamine) is known to influence a variety of psychiatric conditions, such as anxiety and depression. Among the important components in serotonin action is the serotonin transporter protein. Neurons that release serotonin to stimulate Page 733 other neurons also take it up again through the serotonin transporter. The uptake terminates the stimulation and also recycles the molecule for later use. The serotonin transporter became a strong candidate gene for anxiety-related personality traits when it was discovered that the transporter is the target of a class of antidepressants known as selective serotonin reuptake inhibitors. Motivated by the strong suggestion that the serotonin transporter might be involved in anxiety-related traits, researchers looked for evidence of genetic polymorphisms affecting the transporter gene in human populations. This is the l (long) allele, which has an allele frequency of 57 percent among Caucasians. There is also an s (short) allele, in which three of the repeated sequences are not present. The genotypes l l, l s, and s s are found in the Hardy-Weinberg proportions of 32 percent, 49 percent, and 19 percent, respectively (Chapter 15). On the basis of these results, the researchers predicted that the serotonin transporter polymorphism would be found to be associated with anxiety-related personality traits. The predicted result was observed in a study of 505 people who were genotyped for the transporter polymorphism and whose personality traits were classified by means of a self-report questionnaire. Significant associations were found between the transporter genotype and the overall neuroticism score, and the highest correlations were with the anxiety-related traits "tension" and "harm avoidance. Because the s allele is dominant to l with respect to gene expression and personality score, the L Figure 17. The overlap means that the transporter polymorphism accounts for a relatively small proportion of the total variance in neuroticism score in the whole population. In quantitative terms, the transporter polymorphism accounts for 3 to 4 percent of the total variance in neuroticism score and 7 to 9 percent of the genotypic variance in neuroticism score. If all genes affecting neuroticism had the same magnitude of effect as the serotonin transporter polymorphism, approximately 10 to 15 genes would be implicated in the 45 percent of the variance that can be attributed to genetic factors. Genetic and Cultural Effects in Human Behavior Human beings exhibit many important behavioral traits for which no candidate genes have been identified and for which the effects of individual genes are probably too small to detect with genetic linkage studies. For these traits, one measure of the overall importance of genetic factors is the broad-sense heritability, which is the ratio of the genotypic variance in the trait to the total phenotypic variance in the trait. Estimating the heritability of any human behavioral trait requires that special attention be given to cultural transmission of nongenetic factors that potentially affect the behavior. These familial factors increase the resemblance between relatives, and, unless properly taken into account, they inflate the apparent genetic heritability. Most conventional genetic studies of human behavior are biased in that they include cultural transmission in the estimate of heritability, treating the situation as though cultural differences were genetic in origin. Another difficulty in applying the concepts of quantitative genetics to human behavior is that the concept of heritability is prone to being misinterpreted. The most common mistake is to interpret the heritability as applying to genetic differences between populations. For essentially the same reasons that identical twins reared in different environments may have different phenotypes, two genetically identical populations that differ in their environments may differ in average phenotypes. The error in this interpretation is that the heritability of a trait within groups tells one nothing about the genetic or environmental causes of a difference in the average of a trait between groups. Both genetic and cultural factors are relevant to interpreting the variation in phenotypes within a specified population. Use of these quantities for comparison between populations is unjustified and may often lead to incorrect conclusions. Because the emotional overtones of human behavioral differences are so great, the central issue may become clearer by means of analogy. Lacking any knowledge of the genetic relationship between the flocks, we cannot specify the reason for the difference. This is true even though we might know with certainty that the genetic heritability within each flock is 30 percent, because heritability within flocks is irrelevant to the comparison. If the egg laying of the transplanted hens did not change, then the difference between the two groups of hens would have been shown to be entirely genetic. If the egg laying of the transplanted hens did change, then the difference between the groups would have been shown to be environmental. Because experiments of this type cannot be carried out with humans, the issue of genetic versus environmental causes of behavioral differences among human groups is essentially unresolvable. Page 735 Chapter Summary Chemotaxis refers to movement toward attractants and away from repellents. Mutants that are specifically nonchemotactic show no response to a particular attractant or repellent, usually because of a nonfunctional chemosensor protein responsible for binding the particular attractant or repellent. Mutants that are multiply nonchemotactic show no response to a group of chemically unrelated substances, usually because of a nonfunctional chemoreceptor that interacts with a particular subset of chemosensors. Mutants with defects in genes for the components of the common pathway are generally nonchemotactic and fail to respond to any attractant or repellent. Mutations that affect chemotaxis also may cause defects in the structural components of the flagella or in the motor components that control rotational switching. The molecular basis of chemotaxis is mediated by phosphate transfer and methylation. Chemoreceptor proteins repeatedly initiate a chain of phosphorylations, resulting in clockwise flagellar rotation (tumbling). When a chemoreceptor becomes bound with a chemosensor, the phosphoryl groups are rapidly removed, restoring swimming, and the rate of phosphorylation is decreased, so the episodes of swimming get longer. There is also a feedback mechanism because phosphorylation results in removal of certain methyl groups from the chemoreceptors. Demethylation decreases the rate of phosphorylation and, hence, also promotes swimming. Methylation of the chemoreceptors is the basis of sensory adaptation, in which the cells become adjusted to a particular level of an attractant because each additional methyl group increases the level of attractant needed for excitation. Circadian rhythms are cycles synchronized with the 24-hour cycle of day and night. Several mutations in Drosophila alter the period of circadian rhythms and affect such behaviors as locomotor activity, the time of day at which the newly developed adults emerge from the pupa cases, and the courtship song, which refers to the rhythmic patterns of wing vibrations that the male directs toward the female during courtship. Other organisms have different molecular mechanisms that control circadian rhythms. In certain of these conditions, there is also produced a protease-resistant form of the prion protein, which can be transmitted from one organism to another as though it were an infectious agent. Transmissible prion protein has been implicated in kuru in human beings, scrapie in sheep and goats, and mad cow disease (bovine spongiform encephalopathy). Selection experiments for maze-learning ability in laboratory rats demonstrate that a substantial amount of genetic variation affects the trait. The experiments also demonstrate the importance of genotype-environment interaction in complex behaviors. The maze-bright rats were superior to maze-dull rats in learning the maze when motivated by hunger (the condition of the selection), but the maze-dull rats were superior to the maze-bright rats in learning the maze when motivated by escape from water. Furthermore, although rats from the bright strain performed much better than those from the dull strain in a normal environment, the difference was much reduced in an enriched environment and virtually disappeared in a restricted environment. For example, a genetic predisposition to schizophrenia is indicated by the increased risk in close relatives of affected persons, but environmental factors also are important, as shown by the increased risk in normal children adopted into families in which one partner later develops schizophrenia.

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The other daughter molecule contains neither mutation and so has the unmutated target and the amp-s mutation treatment for long term shingles pain purchase anacin overnight. Therefore pain medication for small dogs cheap 525mg anacin with visa, if the transformed cells are plated on medium containing both kanamycin and ampicillin pain medication for dogs aspirin buy anacin in india, only those cells that contain descendants of the mutagenized strand can survive st john pain treatment center buy anacin 525 mg otc, because only these cells are Kan-r as well as Amp-r anesthesia pain treatment center nj generic anacin 525 mg with amex. Furthermore pain medication for dogs surgery buy discount anacin 525mg online, in a typical experiment of this kind, more than 90 percent of the Kan-r Amp-r cells also contain the desired mutation in the target gene. Many genes are too large to be contained completely in a plasmid of the size used for site-directed mutagenesis. In such cases, only a fragment of the target gene is mutated, and then the mutated fragment is isolated from the plasmid and used to replace the nonmutant homologous fragment from the wildtype gene. The amino acid sequence coded by the wildtype and the mutant differ in a single amino acid, with serine replacing cysteine. As expected, the cysteine is critical, and the mutant enzyme was found to be completely nonfunctional. The mutant protein contains a cysteine serine replacement, which renders the enzyme nonfunctional. The customary procedure has been to use a mutant phenotype to recognize a mutant gene and then to identify the wildtype allele and its normal function. This approach has proved highly successful, as evidenced by numerous examples throughout this book. For example, it may prove difficult or impossible to isolate mutations in genes that duplicate the functions of other genes or that are essential for the viability of the organism. As we saw in the previous section, site-directed mutagenesis opens up a quite different approach in which virtually any type of mutation can be created in almost any gene. This approach to genetic analysis is often called reverse genetics because it reverses the usual flow of study: Instead of starting with a mutant phenotype and trying to identify the nature of the mutation, reverse genetics starts with a known mutation and determines its effect on the phenotype. Of course, once a mutation has been created in the laboratory, there remains the problem of how to put it back into a living organism. Germ-Line Transformation in Animals Reverse genetics can be carried out in most organisms that have been extensively studied genetically, including the nematode Caenorhabditis elegans, Drosophila, the mouse, and many domesticated animals and plants. The result of transformation is observed and can be selected in the progeny of the injected animals because of the phenotype conferred by the selectable marker. A somewhat more elaborate procedure is necessary for germ-line transformation in Drosophila. A genetically engineered derivative of this P element, called wings clipped, can make functional transposase but cannot itself transpose because of deletions introduced at the ends of the inverted repeats (Figure 9. For germ-line transformation, the vector is a plasmid containing a P element that includes, within the inverted repeats, a selectable genetic marker (usually one affecting eye color), as well as a large internal deletion that removes much of the transposase-coding region. By itself, this P element cannot transpose because it makes no transposase, but it can be mobilized by the transposase produced by the wings-clipped or other intact P elements. The resulting plasmid and a different plasmid containing the wings-clipped element are injected into the region of the early embryo containing the germ cells. This mobilizes the engineered P vector and results in its transposition into an essentially random location in the genome. Transformants are detected among the progeny of the injected flies because of the eye color or other genetic marker included in the P vector. Integration into the germ line is typically very efficient: From 10 to 20 percent of the injected embryos that survive and are fertile yield one or more transformed progeny. The wings-clipped component is a modified P element that codes for transposase but cannot transpose itself because critical recognition sequences are deleted. Genetically engineered retroviruses containing inserted genes undergo the same process. Animals that have had new genes inserted into the germ line in this or any other manner are called transgenic animals. Another method of transforming mammals uses embryonic stem cells obtained from embryos a few days after fertilization (Figure 9. The mutant stem cells are introduced into another developing embryo and transferred into the uterus of a foster mother (Figure 9. If the embryonic stem cells carry a genetic marker, such as a gene for black coat color, then mosaic animals can be identified by their spotted coats (Figure 9. In this way, mutations introduced into the embryonic stem cells while they were in culture may become incorporated into the germ line of living animals. These strains serve as mouse models for studying the disease and for testing new drugs and therapeutic methods. The procedure for introducing mutations into specific genes is called gene targeting. Campbell 1997 Roslin Institute, Roslin, Midlothian, Scotland Viable Offspring Derived from Fetal and Adult Mammalian Cells the Scottish Finn Dorset ewe known as 'Dolly" is the first mammal to have been cloned from the nucleus of a cell taken from an adult mammal. A spokesperson for People for the Ethical Treatment of Animals was quoted as saying, "It is time that society learned to respect our fellows, not exploit them for every fool thing. Should the clone of a racehorse that won the Triple Crown compete under the same rules as other race-horses? Transfer of a single nucleus at a specific stage of development, to an enucleated unfertilized egg, provided an opportunity to investigate whether cellular differentiation to that stage involved irreversible genetic modification. The first offspring to develop the fact that a lamb was derived from an adult cell confirms that differentiation of that cell did not involve the irreversible modification of genetic material required for development to term. Using the same procedure, we now report the birth of live lambs from adult mammary gland, fetus, and embryo. The fact that a lamb was derived from an adult cell confirms that differentiation of that cell did not involve the irreversible modification of genetic material required for development to term. Our studies with cultured cells suggest that there is an advantage if cells are quiescent. Together our results indicate that nuclei from a wide range of cell types should prove to be totipotent after enhancing opportunities for reprogramming by using appropriate combinations of these cell-cycle stages. In turn, the dissemination of the genetic improvement obtained within elite selection herds will be enhanced by limited replication of animals with proven performance by nuclear transfer of cells derived from adult animals. The lamb born after nuclear transfer from a mammary gland cell is, to our knowledge, the first mammal to develop from a cell derived from an adult tissue. This is consistent with the generally accepted view that mammalian differentiation is almost all achieved by systematic, sequential changes in gene expression brought about by interactions between the nucleus and the changing cytoplasmic environment. These experiments were conducted under the Animals (Scientific Procedure) Act 1986 [United Kingdom] and with the approval of the Roslin Institute Animal Welfare Experiments Committee. Source: Nature 385:810–813 gene-targeting vectors are shown as looped configurations paired with homologous regions in the chromosome prior to recombination. In both cases, cells with targeted gene mutations can be selected by including an antibiotic resistance gene, or other selectable genetic marker, in the sequences that are incorporated into the genome through homologous recombination. Genetic Engineering in Plants A procedure for the transformation of plant cells makes use of a plasmid found in the soil bacterium Agrobacterium tumefaciens and related species. Susceptible plants comprise about 160,000 species of flowering plants, known as the dicots, and include the great majority of the most common flowering plants. Transformed cells are selected in culture by the use of the selectable marker and then grown into mature plants in accordance with the methods described in Section 7. Giant Salmon with Engineered Growth Hormone In many animals, the rate of growth is controlled by the amount of growth hormone produced. Transgenic animals with a growth-hormone gene under the control of a highly active regulatory sequence are often larger than their normal counterparts. An example of a highly active sequence that can drive gene expression is the regulatory region of a gene for metallothionein. They are ubiquitous in eukaryotic organisms and are often encoded in a family of related genes. Human beings, for example, have more than ten metallothionein genes that can be separated into two major groups according to their sequences. The regulatory region of a metallothionein gene accelerates transcription of any genes to which it is attached in response to heavy metals or steroid hormones. Those on the left are normal, whereas those on the right are transgenic animals that contain a salmon growth hormone gene driven by a metallothionein regulatory region. Both the growth-hormone gene and the metallothionein gene were cloned from the sockeye salmon. As an index of scale, the largest transgenic fish on the right has a length of about 42 cm. On average, the transgenic fish are 11 times heavier than their normal counterparts; the largest transgenic fish was 37 times the average weight of the nontransgenic animals. Not only do the transgenic salmon grow faster and become larger than normal salmon, they also mature faster. Engineered Male Sterility with Suicide Genes Another practical application of genetic engineering is in the production of male-sterile plants. Compared with their inbred parents, hybrid plants are usually superior in numerous respects, including higher yield and increased disease resistance (Chapter 16). Male sterility is important in hybrid seed production, because it promotes efficient hybridization between the inbred lines. Cytoplasmic male sterility is widely used in corn breeding (Chapter 14), but analogous mutations are not available in many crop plants. To be optimally useful, male sterility should also be reversible by fertility restorers so that the inbred lines can be propagated. A genetically engineered system of male sterility and fertility restoration has been introduced into a number of plant species, including the oilseed rape, Brassica napus, which is a major source of vegetable oil. Fertility restoration makes use of another protein, called barstar, also produced by B. Barstar is an Page 384 intracellular protein that protects against the lethal effects of barnase by forming a stable, enzymatically inactive complex in the cytoplasm. The reason for the restoration of fertility is that the barstar protein combines with the barnase nuclease and renders it ineffective. The macroscopic appearance and the microscopic appearance of oilseed rape plants of various genotypes are shown in Figure 9. Other Commercial Opportunities As we have seen, organisms with novel phenotypes can be produced by genetic engineering, sometimes by combining the features of different organisms. Note that the fertility-restored plants (E and F) are virtually indistinguishable from wildtype (A and B). The labeled parts of the flowers are A, anther; P, petal; P1, pistil; and N, nectary. Many biotechnology companies are at work designing bacteria that can synthesize industrial chemicals or degrade industrial wastes. Bacteria have also been created that are able to compost waste more efficiently and to fix nitrogen to improve the fertility of soil. A great deal of effort is currently being expended to create organisms that can convert biological waste into alcohol. A number of medicinally or commercially important molecules are routinely produced in genetically engineered cells, including human insulin and growth hormones produced in bacteria. There are also attempts to alter the surface structure of the roots of grains, such as wheat, by introducing genes from legumes (peas, beans) to give the grains the ability that legumes possess to establish root nodules of nitrogen-fixing bacteria. If successful, this would eliminate the need to add nitrogenous fertilizers to soils where grains are grown. An economically important herbicide is glyphosate, a weed killer that inhibits an enzyme in a metabolic pathway found only in plants and microorganisms. Treatment requires that the compound be applied directly to the green foliage of the weeds because it is also toxic to the crop plant itself. However, the target gene of glyphosate is also present in the bacterium Salmonella typhimurium. A resistant form of the gene was obtained by mutagenesis and growth of Salmonella in the presence of glyphosate. Transformation of plants with the glyphosate-resistance gene has yielded varieties of maize, cotton, tobacco, and other plants that are resistant to the herbicide. Thus fields of these crops can be sprayed with glyphosate at any stage of growth of the crop. For example, the black cutworm causes extensive crop damage and is usually combated with noxious insecticides. The bacterium Bacillus thuringiensis produces a protein that is lethal to the black cutworm, but the bacterium does not normally grow in association with the plants that are damaged by the worm. However, the gene coding for the lethal protein has been introduced into the soil bacterium Pseudomonas fluorescens, which lives in association with maize and soybean roots. Reverse genetics makes it possible to isolate and alter a gene at will and introduce it back into a living cell or even the germ line. Besides saving time and labor, reverse genetics enables mutants to be constructed that cannot be formed in any other way. An example is the formation of double mutants of animal viruses, which naturally undergo recombination at such a low frequency that mutations can rarely be recombined by genetic crosses. Production of Useful Proteins Among the most important applications of genetic engineering is the production of large quantities of particular proteins that are otherwise difficult to obtain (for example, proteins that are present in only a few molecules per cell or that are produced in only a small number of cells or only in human cells). Using a vector with a high copy number ensures that many copies of the coding sequence will be present in each bacterial cell, which can result in synthesis of the gene product at concentrations ranging from 1 to 5 percent of the total cellular protein. In practice, the production of large quantities of a protein in bacterial cells is straightforward, but Page 387 there are often problems that must be overcome because, in the bacterial cell, which is a prokaryote, the eukaryotic protein may be unstable, may not fold properly, or may fail to undergo necessary chemical modification. Many important proteins are currently produced in bacterial cells, including human growth hormone, blood-clotting factors, and insulin. Patent offices in Europe and the United States have already issued well over 1000 patents for the clinical use of the products of genetically engineered human genes. These features of retroviruses make them convenient vectors for the genetic manipulation of animal cells, including those of birds, rodents, monkeys, and human beings.

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Practice: Find a description of a research study in a popular magazine prescription pain medication for shingles generic 525mg anacin mastercard, newspaper sciatica pain treatment youtube buy 525mg anacin amex, blog pain treatment hemorrhoids purchase anacin 525 mg overnight delivery, or website pain medication for dogs advil buy discount anacin online. Relationship Between Intrinsic Motivation and Accuracy of Academic Self-Evaluations Among High School Students pain center treatment for fibromyalgia anacin 525 mg sale. This result has been replicated several times (Williamson pain treatment center northside hospital generic 525mg anacin with mastercard, 1998; Pentecost & Garcia, 2006; Armbruster, 2011) Chapter 11 231 11. Recall that the standard sections of an empirical research report provide a kind of outline. Here we consider each of these sections in detail, including what information it contains, how that information is formatted and organized, and tips for writing each section. The title is centered in the upper half of the page, with each important word capitalized. The title should clearly and concisely (in about 12 words or fewer) communicate the primary variables and research questions. This sometimes requires a main title followed by a subtitle that elaborates on the main title, in which case the main title and subtitle are separated by a colon. Here are some titles from recent issues of professional journals published by the American Psychological Association. Below the title are the authors’ names and, on the next line, their institutional afliation—the university or other institution where the authors worked when they conducted the research. As we have already seen, the authors are listed in an order that refects their contribution to the research. When multiple authors have made equal contributions to the research, they often list their names alphabetically or in a randomly determined order. In some areas of psychology, the titles of many empirical research reports are informal in a way that is perhaps best described as “cute. Here are some examples from recent issues of the Journal of Personality and Social Psychology. Positive Emotion Dissociation, Social Connectedness, and Psychological Functioning”. For articles that are being submitted for publication, the title page also includes an author note that lists the authors’ full institutional afliations, any acknowledgments the authors wish to make to agencies that funded the research or to colleagues who commented on it, and contact information for the authors. For student papers that are not being submitted for publication—including theses—author notes are generally not necessary. The abstract presents the research question, a summary of the method, the basic results, and the most important conclusions. Because the abstract is usually limited to about 200 words, it can be a challenge to write a good one. The heading at the top of this page is the full title of the manuscript, with each important word capitalized as on the title page. The introduction includes three distinct subsections, although these are typically not identifed by separate headings. The opening introduces the research question and explains why it is interesting, the literature review discusses relevant Chapter 11 233 previous research, and the closing restates the research question and comments on the method used to answer it. The opening, which is usually a paragraph or two in length, introduces the research question and explains why it is interesting. To capture the reader’s attention, researcher Daryl Bem recommends starting with general observations about the topic under study, expressed in ordinary language (not technical jargon)—observations that are about people and their behavior (not about researchers or their research; Bem, 6 2003). According to Bem, this would be a poor way to begin a research report: Festinger’s theory of cognitive dissonance received a great deal of attention during the latter part of the 20th century (p. For example, the person who knows that he or she enjoys smoking but believes it to be unhealthy may experience discomfort arising from the inconsistency or disharmony between these two thoughts or cognitions. This feeling of discomfort was called cognitive dissonance by social psychologist Leon Festinger (1957), who suggested that individuals will be motivated to remove this dissonance in whatever way they can (p. After capturing the reader’s attention, the opening should go on to introduce the research question and explain why it is interesting. Giving readers a clear sense of what the research is about and why they should care about it will motivate them to continue reading the literature review—and will help them make sense of it. During an orientation meeting at the nursing home, the rules and regulations were explained, one of which regarded the dining room. The dining room was described as similar to a fine restaurant except that tipping was not required. The absence of tipping was a central theme in the orientation lecture, mentioned frequently to emphasize the quality of care along with the advantages of having paid in advance. At the end of the meeting, the friend’s mother was asked whether she had any questions. Immediately after the opening comes the literature review, which describes relevant previous research on the topic and can be anywhere from several paragraphs to several pages in length. Instead, it constitutes a kind of argument for why the research question is worth addressing. By the end of the literature review, readers should be convinced that the research question makes sense and that the present study is a logical next step in the ongoing research process. Like any efective argument, the literature review must have some kind of structure. For example, it might begin by describing a phenomenon in a general way along with several studies that demonstrate it, then describing two or more competing theories of the phenomenon, and fnally presenting a hypothesis to test one or more of the theories. Or it might describe one phenomenon, then describe another phenomenon that seems inconsistent with the frst one, then propose a theory that resolves the inconsistency, and fnally present a hypothesis to test that theory. In applied research, it might describe a phenomenon or theory, then describe how that phenomenon or theory applies to some important real-world situation, and fnally suggest a way to test whether it does, in fact, apply to that situation. Chapter 11 235 Looking at the literature review in this way emphasizes a few things. First, it is extremely important to start with an outline of the main points that you want to make, organized in the order that you want to make them. The basic structure of your argument, then, should be apparent from the outline itself. Second, it is important to emphasize the structure of your argument in your writing. One way to do this is to begin the literature review by summarizing your argument even before you begin to make it. These opening sentences provide the “transitions” that many beginning researchers have difculty with. Instead of beginning a paragraph by launching into a description of a previous study, such as “Williams (2004) found that…,” it is better to start by indicating something about why you are describing this particular study. Here are some simple examples: Another example of this phenomenon comes from the work of Williams (2004). Finally, remember that your goal is to construct an argument for why your research question is interesting and worth addressing—not necessarily why your favorite answer to it is correct. If you want to emphasize the generality of a phenomenon, then of course you should discuss various studies that have demonstrated it. However, if there are other studies that have failed to demonstrate it, you should discuss them too. Or if you are proposing a new theory, then of course you should discuss fndings that are consistent with that theory. However, if there are other fndings that are inconsistent with it, again, you should discuss them too. It is acceptable to argue that the balance of the research supports the existence of a phenomenon or is consistent with a theory (and that is usually the best that researchers in psychology can hope for), but it is not acceptable to ignore contradictory evidence. Besides, a large part of what makes a research question interesting is uncertainty about its answer. The closing of the introduction—typically the fnal paragraph or two—usually includes two important elements. This statement tends to be more formal and precise than in the opening and is often expressed in terms of operational defnitions of the key variables. The second is a brief overview of the method and some comment on its 236 7 appropriateness. Here, for example, is how Darley and Latané (1968) concluded the introduction to their classic article on the bystander efect: these considerations lead to the hypothesis that the more bystanders to an emergency, the less likely, or the more slowly, any one bystander will intervene to provide aid. To test this proposition it would be necessary to create a situation in which a realistic “emergency” could plausibly occur. Each subject should also be blocked from communicating with others to prevent his getting information about their behavior during the emergency. Finally, the experimental situation should allow for the assessment of the speed and frequency of the subjects’ reaction to the emergency. Thus the introduction leads smoothly into the next major section of the article—the method section. An important principle for writing a method section is that it should be clear and detailed enough that other researchers could replicate the study by following your “recipe. At the same time, it should avoid irrelevant details such as the fact that the study was conducted in Classroom 37B of the Industrial Technology Building or that the questionnaire was double-sided and completed using pencils. The method section begins immediately after the introduction ends with the heading “Method” (not “Methods”) centered on the page. Immediately after this is the subheading “Participants,” left justifed and in italics. The participants subsection indicates how many participants there were, the number of women and men, some indication of their age, other demographics that may be relevant to the study, and how they were recruited, including any incentives given for participation. In the frst, the participants section is followed by a design and procedure subsection, which describes the rest of the method. This works well for methods that are relatively simple and can be described adequately in a few paragraphs. In the second approach, the participants section is followed by separate design and procedure subsections. This works well when both the design and the procedure are relatively complicated and each requires multiple paragraphs. Was the independent variable manipulated, and if so, was it manipulated between or within subjects? It often works well to describe the procedure in terms of what the participants did rather than what the researchers did. For example, the participants gave their informed consent, read a set of instructions, completed a block of four practice trials, completed a block of 20 test trials, completed two questionnaires, and were debriefed and excused. In the third basic way to organize a method section, the participants subsection is followed by a materials subsection before the design and procedure subsections. This might mean multiple questionnaires, written vignettes that participants read and respond to , perceptual stimuli, and so on. The results section is where you present the main results of the study, including the results of the statistical analyses. Although it does not include the raw data—individual participants’ responses or scores—researchers should save their raw data and make them available to other researchers who request them. Although there are no standard subsections, it is still important for the results section to be logically organized. One is whether any participants or responses were excluded from the analyses and why. The rationale for excluding data should be described clearly so that other researchers can decide whether it is appropriate. A second preliminary issue is how multiple responses were combined to produce the primary variables in the analyses. For example, if participants rated the attractiveness of 20 stimulus people, you might have to explain that you began by computing the mean attractiveness rating for each participant. Or if they recalled as many items as they could from study list of 20 words, did you count the number correctly recalled, compute the percentage correctly recalled, or perhaps compute the number correct minus the number incorrect? This is where you would present test-retest correlations, Cronbach’s α, or other statistics to show that the measures are consistent across time and across items. The results section should then tackle the primary research questions, one at a time. One approach would be to answer the most general questions and then proceed to answer more specifc ones. Another would be to answer the main question frst and then to answer secondary ones. The rest of the steps involve presenting the research question and the answer to it in words. In fact, the basic results should be clear even to a reader who skips over the numbers. Suggestions for future research the discussion typically begins with a summary of the study that provides a clear answer to the research question. In a short report with a single study, this might require no more than a sentence. In a longer report with multiple studies, it might require a paragraph or even two. The summary is often followed by a discussion of the theoretical implications of the research. Although you do not have to provide a defnitive explanation or detailed theory for your results, you at least need to outline one or more possible explanations. In applied research—and often in basic research—there is also some discussion of the practical implications of the research. The theoretical and practical implications are often followed by a discussion of the study’s limitations. Perhaps there is some evidence that participants did not fully understand their task or that they were suspicious of the intent of the researchers.

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From a perspective of conserving strength wrist pain treatment tendonitis cheap anacin 525 mg without a prescription, air forces will also have to be cognisant of the need to protect the expensive and pain relief treatment for sciatica discount anacin 525mg fast delivery, at times pain treatment for lupus cheap anacin 525mg otc, limited quantity of assets that they possess pain medication for dogs with renal failure discount anacin 525mg with visa, a direct impact of their cost-intensive nature groin pain treatment video order anacin 525mg fast delivery. While preparing plans for operations pain relief treatment center llc buy anacin paypal, air forces must take into account the state of readiness of the adversary forces and avoid their strongly defended areas while attempting to exploit weaknesses in their air defences. If the adversary is seen to be well prepared and of equal capability to one’s own air forces, it may even be necessary to postpone the planned campaign while other methods to weaken their position are investigated. Sun Tzu advised avoiding perfect formations, which in modern confict would translate to a broader joint framework that would include control of the air and the surface battlespace. The requirement to have control of the air for the success of all other operations is an unassailable maxim that can only be disregarded at great peril. When faced with an equally capable adversary, it would be prudent either to build up one’s own air power capabilities to a higher level before embarking on confict or undermine the strength of the opposing air force through either covert or overt actions. The concept of pre-emptive strikes comes into prominence under these circumstances. In air campaigns, adapting to changing circumstances by optimising the inherent fexibility of air power is a critical component of winning strategies. Air power’s reliance on technology entails the need for detailed planning for the success of air campaigns The possibility of technical failures brings an element of uncertainty to air operations As far as possible, an adversary with parity in air power capabilities should not be directly confronted 212 Manoeuvre The Artful Strategy these are axioms of the Artful Strategy— Do not advance uphill, Nor oppose an enemy whose back is against a hill. Do not pursue when flight is feigned; Do not attack when the enemy is keen; Do not swallow a bait; or thwart a withdrawing force; Do not press a besieged force, but leave a passage. The fundamentals of employing forces depend on terrain, subterfuge and the defeated opponent. When the enemy occupies high ground, do not confront him uphill; and when his back is secured by being against a hill, do not make a frontal assault. When the enemy pretends to fee, do not pursue; do not attack their elite troops; and do not accept a profered bait. Sun Tzu ended some of the chapters in the treatise with a concluding summary of the basic rules of warfare explained in the context of the main topic discussed in that particular chapter. This chapter is concluded with few generic axioms, some at the operational level that deal with direct confrontation. The axioms relate positioning to the terrain, adversary subterfuge and the possible ways to deal with a defeated force. The frst rule is about basic positioning that Sun Tzu explained through the simile of hills. He advised not to attack an adversary whose position is difcult to approach or one who is in a strong and concentrated defensive position. Under both these conditions, the efort should be to force the adversary to defend multiple positions, thereby making them split their forces and weakening their concentration. Commanders have to be careful not to fall prey to the adversary’s subterfuge which could take the form of a feigned retreat to draw one’s forces into an ambush, or an ofer of easy victory in some areas even as they are preparing to strike elsewhere while one is thus distracted or creating the illusion of their strongest points being weak spots susceptible to attack. While it is necessary in confict to pursue the retreating adversary, this must be done after determining the cause for their backing down and an adversary ofering a concession without sufcient 213 The Art of Air Power cause should always be taken as a possible misleading cue. The basic concept is that if a position is not cleanly won, then one should be suspicious about the adversary’s intent. For example, if the enemy puts some booty before you, you ought to believe that within it there is a hook and that it conceals some trick. If many of the enemy are put to fight by your few, if a few of the enemy assail your many, if the enemy turns in sudden fight, … you ought to fear a trick. And you should never believe that the enemy does not know how to carry on his afairs; rather, if you hope to be less deceived … and … run less risk, in proportion as your enemy is weaker, in proportion as he is less cautious, you should the more respect him. Niccolo Machiavelli the Art of War, 1521 Sun Tzu advocates fairly easy terms to deal with a defeated force—that they must not be pressed too hard and that they should be allowed to go back if they are genuinely withdrawing. Most commentators explain this fairly signifcant advice in terms of portraying a defeated force returning home as willing to fght to the death if their path is barred with no possible escape route being made available. However, there is another school of thought that interprets this to mean that the adversary should be ofered a way out, and when that route is accepted, their courage born of desperation will be drained and they can be easily annihilated. The author subscribes to the latter interpretation because, all through the treatise, Sun Tzu supports the concept of total defeat of the adversary once battle has been joined. Further, since the maxim has probably been adapted from another older book, it is possible that Sun Tzu deliberately left the stanza open to varied interpretations unlike other stanzas that he has himself composed. Even while not pressing a desperate adversary or turning a withdrawing force into a desperate adversary willing to fght to the death, one must employ a certain amount of subterfuge to making them believe that they are safe before carrying out the fnal strike. The three fundamentals regarding the employment of forces discussed in this stanza have air power connotations at the operational and strategic levels. At the operational level of the air campaign, one must always be aware of the adversary position and avoid engagements from an unfavourable position at all times. The use of subterfuge by the adversary is more common in air operations and perhaps more difcult to pinpoint at all times. The dynamic nature of the air campaign means that the challenge for the adversary will be to protect their centres of gravity in ways that make an attack on them seem ‘uphill’. The attempt will be to try to portray centres of gravity as unassailable, that is protected by a ‘virtual hill’. It is easier to fall for adversary subterfuge at the operational level of an air campaign, wherein a lure could be sent out to draw one’s own air combat assets into a pre-planned ambush. The chances of such actions in the contemporary scenario of limited wars and one-sided air campaigns are minimal. From an air power perspective, dealing with a defeated adversary force is also a comparatively smaller task, since defeated air forces will not have the capability to mount a credible fghtback. Valuable air assets should not be risked or wasted in pressing an already beaten adversary, but conserved for the ofensive campaign. The strategy explains how best to advance one’s own position while expending the minimum amount of energy and achieving the best results for oneself. The use of subterfuge is common in air campaigns and easily carried out A defeated air force will not be able to fght back credibly and, therefore, may not warrant a fnal blow of annihilation Adversary centres of gravity can be made to appear well protected against air attacks 215 The Art of Air Power Conclusion this chapter is predominantly concerned with the manoeuvres of a force to obtain a position of advantage and the large number of variables that directly and indirectly impact on its ability do this efciently. The variables also combine in diferent permutations to create an even more diverse number of situations that a commander will have to consider in his planning and execution of the campaign. Air power’s inherent characteristics of responsiveness, reach, penetration, tempo of operations and lethality make the air campaign one of rapid and decisive ‘manoeuvre’. Further, swiftness and aggression, the two cardinal elements in manoeuvre warfare, are ideally suited for the employment of air power within the broader campaign. The success of a campaign is dependent on the strategic plans being secure and well formulated, encompassing sufcient fexibility to permit lower level plans to be adapted in the course of the confict. An air campaign plan will have to be formulated within a very broad framework because of the dynamic nature of air operations so that sufcient adaptability is retained within the plan at all times to cater for operational requirements in the short term. However, such adaptability must stay within the bounds of the strategic plan and be continuously oriented towards achieving the laid down objectives. Within the context of manoeuvre warfare, air power provides some critical capabilities. The advantageous positioning of forces is much more easily achieved through the use of air mobility and sufciency of airlift ensures that the logistic supply chain is always maintained at the appropriate level. A prerequisite for the smooth and efcient functioning of these capabilities is control of the air, which is the core task of all air forces at all times. In contemporary ‘irregular warfare’ scenarios, air mobility is a prized capability because of its utility as an enabler to exploit time sensitive windows of opportunities in the battlespace. While the actual operations of this nature will be at the tactical level, the planning and coordination will have to be carried out at the strategic level of command in order to maintain centralised control over these scarce assets. A major factor that Sun Tzu highlights in the chapter is the use of subterfuge or deception to confuse the adversary as one part of a broader strategy of confict avoidance. The other part of confict avoidance is based on deterrence and in both cases air power capabilities make crucial contributions at the strategic and operational levels. Further, the concept of deception, which would form part of indirect action, as being fundamental to the success of a confrontational engagement with an adversary is one of Sun Tzu’s major axioms. This is also amply supported by air power capabilities like carrying out decoy operations, creating ‘virtual hills’ that are insurmountable for the adversary and rapid deployments that difuse the focus of the enemy. This is particularly valuable for nations that lack geographic depth when entering into confict situations. In contemporary confict situations, control of the air is a vital contributory factor to maintaining the morale of the forces. It has been demonstrated over the years that constant aerial harassment can very rapidly sap the morale of otherwise robust forces, leading to certain defeat. This can only be avoided through adequate control of the air over the territories in which one’s own forces are operating. Morale is also inexplicably connected to the capability and skill of the leadership. In fact, Sun Tzu explains the need for composure in commanders and draws the thread across to its impact on the morale of the force in a clear manner. This human factor is one of the major factors that cannot be clearly quantifed in combat conditions and needs careful nurturing at all levels of command. Sophisticated commanders will always be able to judge the morale of their own forces while being able to initiate actions that will undermine that of the adversary forces. It means that by its very nature confict is unpredictable and a force must possess an inherent capacity to adapt to change in order to be successful. In fact, Sun Tzu makes it clear throughout the treatise that strategy requires to be adapted continuously to suit the emerging requirements at all levels of warfare—from the grand strategic to the tactical. In his assessment, strategy is seen as a systemic process that follows a laid down set of rules and uses well defned methods to formulate the most appropriate, yet fexible, plan to address emerging situations comprehensively in a contextual manner. A distinctive combination of possible variations makes each context The Art of Air Power in confict unique and, therefore, operations must be adapted based on the advantages and disadvantages that can be perceived as the strategy unfolds during the progress of a campaign. Sun Tzu refers to two kinds of advantages; one that occurs during the conduct of a campaign that in itself is following a well-defned strategy, clearly indicative of the veracity of the strategy, and the other that is consciously created by a sophisticated commander through the skilful manoeuvring of the force in relation to the adversary. Disadvantages being considered in this concept are premised to afect the adversary and provide a winning edge to the strategy being followed by one’s own forces. Sun Tzu believed that successful commanders will always be able to recognise and exploit the disadvantages of the adversary while shielding one’s own from being identifed. Skilfully adapting the strategy to cater for emerging situations is a primary requirement for the efcacy of this concept of manipulating advantages and disadvantages. The chapter explains the possible variations that could occur in confict and addresses the question of rapid response to unforeseen contingencies that arise. Sun Tzu also cautions commanders not to become infexible in following what was a winning strategy on previous occasions, since such an approach will inhibit free adaptation after the confict has been initiated. In keeping with the theme of the treatise, that winning without fghting a war is the pinnacle of leadership, the chapter also indicates that, even if one’s own forces are clearly superior to the adversary, circumstances could develop wherein confrontation should be avoided at all costs. At the end of the chapter Sun Tzu also alludes to certain character traits that make leaders weak, even though they may have the skill and the expertise to be adaptable in enforcing the strategy for a confict. This is interesting because as a general rule Sun Tzu’s maxims do not elaborate on the personal character traits of commanders but focus on the need for leaders and commanders to be well versed in the formulation and implementation of strategy and to have the ability to be decisive in confict. Sun Tzu proposes the principle of ‘preparedness through adaptability’, even for unforeseen contingencies, as the optimum method to avoid defeat in confict. However, avoiding defeat is only one part of conducting a campaign, the other being securing assured victory. In order to ensure victory, the commander must be adept at recognising emerging opportunities—created through one’s own advantage or through exploiting the adversary’s disadvantage—and simultaneously adapting the strategy to exploit the opportunity to the maximum. Flexibility is a basic principle of developing an adaptable strategy but the employment of fexibility, especially in confict situations, to adapt strategy during the progress of a campaign must be done within well-defned rules in order to be successful. While extolling the virtues of adaptability, Sun Tzu also makes it very clear that it has to be done within the ambit of a set of laid down rules. The implementation of an adaptive strategy being ‘fnetuned’ through the fexibility of the force while in confict is a creative and complicated enterprise. Controlling creativity is the domain of the commander and, therefore, the success or failure of a strategy—that 220 Adapting to Change in turn determines victory or defeat—is dependent on the force having a skilled and sophisticated strategic commander. Sun Tzu has dealt with the topic of this chapter, adaptability, almost as an introduction to the next three chapters that provide detailed injunctions for dealing with a number of specifc situations that arise in confict. In combination, they cover a very large spectrum of possible situations and Sun Tzu gives commanders guidelines to ensure success in each of them. A horse with no bridle is useless, but equally bad is the horse whose reins you pull at every turn, in a vain efort at control. Control comes from almost letting go, holding the reins so lightly that the horse feels no tug but senses the slightest change in tension and responds as you desire. Robert Green the 33 Strategies of War, 2006 Generally in war, the commander Receives the mandate from the sovereign, Then gathers the troops and assembles a Force. The general rule for military operations is that the military leadership receives the order from the civilian leadership and then mobilises the troops and assembles the army, judged to best meet the sovereign’s objectives. This stanza is a repeat of the opening stanza of Chapter 7 and, therefore, a large number of commentators have opined that it has been interpolated here purely to provide a continuity to the treatise because the chapter otherwise goes directly into explaining the strategy to deal with numerous variations. Essentially this states in very bald terms that military forces should be mobilised and employed only on the direct orders of the civilian government. The nuances of this fundamental factor in terms of both contemporary operations and air power in particular have already been examined in the previous chapter and as such their repetition here is considered superfuous. In surrounded situations, resort to stratagem; In desperate situations, do battle. Where paths cross— physically, as in highways and virtually in terms of national objectives—join forces with allies. Do not linger on dangerously isolated positions, use stratagem in enclosed, hemmed-in situations and fght last-ditch battles when in desperate situations. Tere are some routes which must not be followed, some forces that must not be attacked, some cities which must not be besieged, some territory that must not be contested, and some orders of civilian governments which need not be obeyed. Strategic adaptations should be done with respect to the geographical terrain as well as the execution of plans. Although Sun Tzu elaborated on the actions to be taken in fve specifc terrains, the stanza can also be explained at the strategic level of planning. The basic maxim is that the envelope within which all strategies have to be planned and executed is always constrained and determined by one’s position and situation.

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