Jeffrey A Brinker, M.D.
- Professor of Medicine
- Joint Appointment in Radiology and Radiological Science
One night not long afterward cheap femara 2.5mg otc xenoestrogens menopause, that particular hacker leapt off the Harvard Bridge into the ice-covered Charles River and was severely injured order generic femara online breast cancer 9mm tumor. And after every few instructions there would be another punch line in this sublime form of communication order femara 2.5 mg visa women's health issues in japan. While conceding that hacker relationships were unusual, especially in that most hackers lived asexual lives, Fredkin would later say that "they were living the future of computers. Save for the last trait, Greenblatt at first thought him well within the spectrum of random people who might wander into the lab. The fact that Merton was such a good chess player pleased Greenblatt, who was then working to build an actual computer which would run a souped-up version of his chess program. He assumed a classic position of catatonia, rigidly sitting upright, hands clenched into fists at his side. He would not respond to questions, would not even acknowledge the existence of anything outside himself. The incident severely shook the hackers, including Greenblatt, who found out about the incident when he returned from a holiday visit home. Nonetheless, Greenblatt immediately drove out to Westboro State Hospital to recover Merton. It was a long drive, and the destination reminded Greenblatt of something out of the Middle Ages. The last step in this tortuous process was getting the signature of an elderly, apparently senile doctor. Unlike most catatonics, Merton would improve after a few days, especially when he was given medicine. Often, when he went catatonic somewhere, whoever found him would call someone to take him away, and the doctors would give a diagnosis of permanent catatonia even as Merton was coming to life again. The letter explained that Louis was a strange boy, and he sometimes would go stiff. In that case, all you needed to do was to ask, "Louis, would you like to play a game of chess? The game got under way, with Fredkin chatting away in a rather one-sided conversation, but suddenly Merton just stopped. Once Greenblatt went to Fredkin to ask him to help out; Fredkin went back with Greenblatt to find Merton stiff and unresponsive. As much as any devout religious order, the hackers had sacrificed what outsiders would consider basic emotional behavior for the love of hacking. David Silver, who would eventually leave the order, was still in awe of that beautiful sacrifice years later: "It was sort of necessary for these people to be extremely brilliant and, in some sense, handicapped socially so that they would just kind of concentrate on this one thing. The computer world outside Cambridge did not stand still while the Hacker Ethic nourished on the ninth floor of Tech Square. But the heart of the movement was this: people who wanted to hack were finding computers to hack on. Centers of hacker culture were growing at various institutions around the country, from Stanford to Carnegie-Mellon. A programmer named Mike Levitt began a leading-edge technology firm called Systems Concepts in San Francisco. All in all, the small company managed to get a lot of the concentrated talent around Tech Square out to San Francisco. This was no small feat, since hackers were generally opposed to the requirements of California life, particularly driving and recreational exposure to the sun. It happened to be the coldest day of the Cambridge winter that year, and as soon as he walked outside his glasses cracked from the sudden change of temperature. So some surprising offer would come to those persons, or some visit arranged, usually someplace far, far away. The difference began with the setting, a semicircular concrete-glass-and-redwood former conference center in the hills overlooking the Stanford campus. Inside the building, hackers would work at any of sixty-four terminals scattered around the various offices. A Stanford hacker named Donald Woods discovered a kind of game on a Xerox research computer one day that involved a spelunker explorer seeking treasure in a dungeon. Like any good system or program, of course, Adventure was never finished Woods and his friends were always improving it, debugging it, adding more puzzles and features. It was at Stanford that gurus were as likely to be faculty people as systems hackers (among Stanford professors was the noted computer scientist Donald Knuth, author of the multivolume classic the Art of Computer Programming). It was at Stanford that, before the Adventure craze, the casual pleasures of Spacewar were honed to a high art (Slug Russell had come out with McCarthy, but it was younger hackers who developed five-player versions and options for reincarnation, and ran extensive all-night tournaments). It was at Stanford that hackers would actually leave their terminals for a daily game of volleyball. It was at Stanford that the computer could support video images, allowing users to switch from a computer program to a television program. In a paper summarizing the history of the Stanford lab, Professor Bruce Buchanan refers to the "strange social environment created by intense young people whose first love was hacking," and it was true that the lengths that hackers went to in California were no less extreme than those at Tech Square. After you made your food purchase, you were given the option to double-or-nothing the cost of your food, the outcome depending on whether it was an odd or even-numbered millisecond when you made the gamble. It was open to outsiders, who would sit down and begin hacking; and if they showed promise, Uncle John McCarthy might hire them. At one point, presumably by mistake, a robot got loose and was careening down the hill when, fortunately, a worker driving to the lab spotted it, and rescued it. Some of the hackers got heavily involved in a computer music project that would break ground in that field.
An opening paragraph gives an overview of the chapter purchase femara 2.5mg online women's health clinic orange park fl, illustrates the subject with some specific examples purchase femara 2.5mg without a prescription menopause sleep, and shows how the material is connected to purchase femara now women's health tipsy basil lemonade genetics as a whole. The text makes liberal use of numbered lists and "bullets" in order to help students organize their learning, as well as summary statements set off in special type in order to emphasize important principles. There is a Page xvi Concise Dictionary of Genetics at the end of the book for students to check their understanding of the Key Terms or look up any technical terms they may have forgotten. The Dictionary includes not only the Key Terms but also genetic terms that students are likely to encounter in exploring the Internet or in their further reading. Contents the organization of the chapters is that favored by the majority of instructors who teach genetics. An important feature is the presence of an introductory chapter providing a broad overview of genes—what they are, how they function, how they change by mutation, and how they evolve through time. The introductory chapter serves to connect the more advanced concepts that students are about to learn with what they already know. It also serves to provide each student with a solid framework for integrating the material that comes later. Throughout each chapter, there is a balance between observation and theory, between principle and concrete example, and between challenge and motivation. Chapter 1 is an overview of genetics designed to bring students with disparate backgrounds to a common level of understanding. This chapter enables classical, molecular, and evolutionary genetics to be integrated in the rest of the book. Included in Chapter 1 are the basic concepts of genetics: trait, gene, genotype, phenotype, gene interaction, and so forth. Also included is the basic probability framework of Mendelian genetics and the testing of genetic models by means of the chisquare test. An important principle of genetics, too often ignored or given inadequate treatment, is that of the complementation test and how complementation differs from segregation or other genetic principles. Chapter 2 includes a clear and concise description of complementation, with examples, showing how complementation is used in genetic analysis to group mutations into categories corresponding to genes. This chapter also introduces the use of molecular markers, especially with reference to human genetic analysis, because these are the principal types of genetic markers often used in modern genetics. This example illustrates the value of basic research in leading, often quite unpredictably, to practical applications. Also included is the subject of the human genome with special reference to human chromosome number and structure and the types of aberrations that are found in human chromosomes. Also discussed are methods used in the analysis of complex genomes, such as the human genome, in which a gene that has been localized by genetic mapping to a region of tens of millions of base pairs must be isolated in cloned form and identified. These chapters include the principles of gene expression, gene regulation, and the genetic control of development. The chapter on development focuses especially on genetic analysis of development in nematodes (Caenorhabditis elegans) and Drosophila, and there is a thorough examination of the exciting new work on the genetic basis of floral development in Arabidopsis thaliana. Chapter 13 covers the molecular details of mutation and the effects of mutagens, including new information on the genetic effects of the Chernobyl nuclear accident. This chapter also includes a section on mad cow disease and its relation to the molecular basis of biological rhythms. There is also a section on the genetic determinants of human behavior with examples of the approach using "candidate" genes that led to the identification of the "natural Prozac" polymorphism in the human serotonin transporter gene. Connections A unique special feature of this book is found in boxes called Connections. All of the Connections include short excerpts from the original literature of genetics, usually papers, each introduced with a short explanatory passage. More than a quarter were published more recently than 1980, including the paper in which the cloning of the sheep Dolly was reported. The pieces are called Connections because each connects the material in the text to something that broadens or enriches its implications. Some of the Connections raise issues of ethics in the application of genetic knowledge, social issues that need to be addressed, or issues related to the proper care of laboratory animals. Because each Connection names the place where the research was carried out, the student will learn that great science is done in many universities and research institutions throughout the world. In papers that use outmoded or unfamiliar terminology, or that use archaic gene symbols, we have substituted the modern equivalent because the use of a consistent terminology in the text and in the Connections makes the material more accessible to the student. Genetics on the Internet More than in most fields of biology, genetic resources and genetic information are abundant on the Internet. A recent search of Internet sites using the Alta Vista search engine and the keyword genetics yielded about 500,000 hits. Most of these are of limited usefulness, but quite a few are invaluable to the student and to the practicing geneticist. One reason for developing these exercises is that genetics is a dynamic science, and most of the key Internet resources are kept up to date. Continually updated, the Internet exercises introduce the newest discoveries as soon as they appear, and this keeps the textbook up to date as well. Instead, the sites are accessed through the use of key words that are highlighted in each exercise. The use of key words also allows an innovation: one exercise in each chapter makes use of a mutable site that changes frequently in both the site accessed and the exercise. The instructor may wish to make short assignments from some of them, or use them for extra credit or as short term papers. We have included a suggested assignment for each of the exercises, but many instructors may wish to develop their own. We would be pleased to receive suggestions for new web exercises at the Jones and Bartlett home page:
A treatment planning inter-comparison of proton and intensity modulated photon radiotherapy order femara with visa frautest menopause. Potential role of intensity-modulated photons and protons in the treatment of the breast and regional nodes purchase femara australia menstruation longer than 7 days. Intensity modulation in radiotherapy: photons versus protons in the paranasal sinus femara 2.5mg with mastercard pregnancy questions hotline. Proton therapy for pediatric cranial tumors: preliminary report on treatment and disease-related morbidities. Monte Carlo calculated stopping-power ratios, water/air, for clinical proton dosimetry (50-250 MeV). Potential improvement of three dimension treatment planning and proton therapy in the outcome of maxillary sinus cancer. Potential role of proton therapy in the treatment of pediatric medulloblastoma/primitive neuro-ectodermal tumors: Spinal theca irradiation. Optimization of 3D Radiation Therapy with both Physical and Biological End Points and Constraints. Calculation of the spatial variation of relative biological effectiveness in a therapeutic proton field for eye treatment. Nuclear Interactions in Proton Therapy: Dose and Relative Biological Effect Distributions Originating From Primary and Secondary Particles. Radiobiological significance of beam line dependent proton energy distributions in a spread-out Bragg peak. Monte Carlo simulations with time-dependent geometries to investigate organ motion with high temporal resolution. Accurate Monte Carlo for nozzle design, commissioning, and quality assurance in proton therapy. Pedroni E, Bacher R, Blattmann H, Boehringer T, Coray A, Lomax A, Lin S, Munkel G, Scheib S, Schneider U, Tourovsky A. The 200-MeV proton therapy project at the Paul Scherrer Institute: Conceptual design and practical realization. Thresholds for human detection of patient setup errors in digitally reconstructed portal images of prostate fields. Effects of respiratory motion on dose uniformity with a charged particle scanning method. Radiobiological Studies of a High-Energy Modulated Proton Beam Utilizing Cultured Mammalian Cells. Chondrosarcoma of the base of the skull: a clinicopathologic study of 200 cases with emphasis on its distinction from chordoma. Shioyama Y, Tokuuye K, Okumura T, Kagei K, Sugahara S, Ohara K, Akine Y, Ishikawa S, Satoh H, Sekizawa K. Distal penetration of proton beams: the effects of air gaps between compensating bolus and patient. The potential for proton beam therapy in locally advanced carcinoma of the cervix. Analysis of the relationship between tumor dose inhomogeneity and local control in patients with skull base chordoma. Thornton A, Fitzek M, Varvares M, Adams J, Rosenthal S, Pollock S, Jackson M, Pilch B, Joseph M. Optimization of Beam Parameters and Treatment Planning for Intensity Modulated Proton Therapy. Potential clinical gain of proton (and heavy ion) beams for brain tumors in children. A treatment plan comparison of intensity modulated photon and proton therapy for paraspinal sarcomas. Benign meningioma: Partially resected, biopsied, and recurrent intracranial tumors treated with combined proton and photon radiotherapy. A phenomenological model for the relative biological effectiveness in therapeutic proton beams. Diagnose and treat patients with psoriasis using treat-to-target guidelines this activity as designed and achieving a passing score on the post-test, you. Select appropriate biologic therapies for patients with psoriasis will be directed to a Web page that will allow you to receive your certifcate of Disclosure Declarations credit via e-mail or you may print it out at that time. The online post-test and Individuals in a position to control the content of this educational activity are evaluation can be accessed at tinyurl. Consultant: Postgraduate Institute for Medicine is jointly accredited by the American AbbVie Inc. Target Audience this journal supplement is intended for dermatologists, residents, internists, Jashin J. Psoriasis—a chronic, infammatory, immune-system disease that affects approximately 8 million Americans—is often underdiagnosed. The Postgraduate Institute of Medicine planners and disease, and psoriatic arthritis. Such Many clinicians fail to select a therapeutic option that addresses the needs of material is identifed within the text of the articles. Complicating the situation is the fact that many clinicians do oped from interviews with the faculty.
Without chromosome condensation buy femara amex xanthelasma menopause, the chromosomes would become so entangled Figure 6 order femara visa menstrual 2 days late. Each of these chromosomes has a length and cross-sectional diameter many times greater than those of the corresponding chromosome at mitotic metaphase in ordinary somatic cells discount femara 2.5 mg without prescription women's health clinic toledo ohio, as well as a constant and distinctive pattern of transverse banding (Figure 6. Polytene chromosomes are atypical chromosomes and are formed in "terminal" cells; that is, the larval cells containing them do not divide and are eliminated in the formation of the pupa. Although they do not contribute to the tissues in the adult fly, the polytene tissues of larvae have been especially valuable in the genetics of Drosophila, as will become apparent in Chapter 7. Because the two largest chromosomes in Drosophila (chromosomes numbered 2 and 3) have centrally located centromeres, the chromosomes appear in the configuration shown in Figure 6. In a male, the Y chromosome, which consists almost entirely of heterochromatin, is incorporated in the chromocenter. The darkly staining transverse bands in polytene chromosomes have about a tenfold range in width. These bands result from the side-by-side alignment of tightly folded regions of the individual chromatin strands that are often visible in mitotic and meiotic prophase chromosomes as chromomeres. This linear array of bands, which has a pattern that is constant and characteristic for each species, provides a finely detailed cytological map of the chromosomes. The banding pattern is such that observers with sufficient training and experience can identify short regions in any of the chromosomes (Figure 6. Because of their large size and finely detailed morphology, polytene chromosomes are exceedingly useful for a process called in situ nucleic acid hybridization. The somatic chromosomes of Drosophila, drawn to scale with respect to the polytene fourth chromosome, are shownat the upper right as they appear in mitotic prophase. The chromocenter is the central region in which the centromeric regions of all chromosomes are united. However, in eukaryotes, some components of the genome can be detected because their base composition is quite different from the average of the rest of the genome. Information about the size of repeated sequences and the number of copies of a particular sequence can be obtained through studies of the rate of renaturation. Thus if each solution is separately denatured and renatured, the molecules of T7 will renature more rapidly than those of T4. If the two solutions are instead mixed, the T7 and T4 will renature independently of one another (because they are not homologous), and a curve such as that in Figure 6. Note that the curve consists of two steps, one for the more rapidly renaturing T7 molecules and the other for the T4 molecules. If such molecules are fragmented into many components of equal size, then the molar concentration of each component will be the same as that of the unbroken Figure 6. The times required for half-completion of renaturation, t1/2, are obtained by drawing the red horizontal lines, which divide each curve equally in the vertical direction, and then extending the red vertical lines to the time axis. In contrast, if a molecule with an overall sequence that includes both a unique component and several copies of different repeated sequences is fragmented, fragments containing the more numerous repeated sequences will renature more rapidly than the fragments containg portions of the unique sequence. For example, consider a molecule containing 50,000 base pairs and consisting of 100 copies of a tandemly repeated sequence of 500 base pairs. If the molecules are broken into about 100 fragments of roughly equal size, each fragment will be about 500 base pairs. Althugh the renaturation curve for the fragments will have a single step, the renaturation rate will be characteristic of molecules 500 nucleotides in length. If a genome contains multiple families of repeated sequences whose abundances differ, the renaturation curve will have steps—one step for each repeating sequence. Renaturation kinetics can be described in a simple mathematical form, because the reaction is one in which the ratelimiting step is the initial collision of two molecules. The expression C0t is commonly called cot, and a plot of C/C0 versus C0t is called a cot curve. When renaturation is half completed, C/C0 = 1/2 and the value of 1/k depends on experimental conditions, but for a particular set of conditions, the value is proportional to the number of bases in the renaturing sequences. The longer the sequence, the greater will be the time to achieve half-complete renaturation for a particular strating concentration (because the number of molecules will be smaller). If a molecule consists of several subsequences, then one needs to know C0 for each subsequence, and a set of values of 1/k will be obtained (one for each step in the renaturation curve), each value depending on the length of the subsequence. What is meant by the length of the sequence that determines the rate is bese described by example. Experimentally, the number of bases per repeating unit is not determined directly. Generally, renaturation curves for a series of molecules of known molecular weight with no repeating elements in their sequences (and hence yielding one-step renaturation curves) serve as standards. With the standard conditions for Cot analysis used to obtain this set of curves, the sequence length N (in base pairs) that yields a particular value of C0t1/2 is in which t is in seconds, C is in nucleotides per liter, and 5 × 105 is a constant dependent on the conditions of 0 renaturation. Through this formula, the experimentally determined value of Cot (C0t1/2) yields an estimate of the repeat length, N, of a repetitive sequence. How one obtains the necessary value of C0 will become clear when we analyze a Cot curve. Such an analysis begins by first noting the number of steps in the curve (each step of which represents a sequence or class of sequences of a particular length) Page 238 and the fraction of the material represented by each step. The observed value of C0t1/2 for each step must be corrected by first inferring the value of C0 for each sequence class. The lengths of the sequences are then determined from these corrected values by comparison to standards, and the sequence lengths and sequence abundances, as a proportion of the total, are compared to obtain the number of copies of each sequence. The scale at the top of the figure was obtained from Cot analysis of molecules that 0 1/2 have unique sequences of known lengths, as in Figure 6.
Smaller companies needing fewer litres of potable water a day might find it cheaper to discount 2.5mg femara womens health nurse practitioner jobs continue with water delivery purchase femara 2.5 mg free shipping menstrual 10 days late. Many factories in Southeast Asia generic femara 2.5mg with amex menstruation vaginal itching, Bangladesh and large parts of Africa also have poor-quality drinking water. Tai Yang benefited from its parent company in Taiwan, China, a technologically advanced nation. Other enterprises without the financial means for water investment might consider alternative sources of technical and financial support. In the garment industry, the wealthier manufacturers and retailers that profit from lower-wage labour in developing nations might also donate money or technology as a sign of goodwill. Nike’s code of conduct was successfully adopted in Viet Nam and led to improvements in workers’ access to proper meals and clean water (see Tae Kwang Vina, Chapter 4). Poor water is such a widespread concern that any agency interested in improving health and productivity should consider workplace-based water filtration systems. Of course, the people around Phnom Penh, not just the factories, suffer from water contamination. With its filtration system now up and running, 350 Clean drinking water Tai Yang might consider allowing workers to take a few litres of water home each day. Union/employee perspective the demand for better drinking water was not entirely home grown. In 1999, Cambodia and the United States entered into a three-year Trade Agreement on Textile and Apparel. Cambodia’s garment industry came under the watchful eye of international scrutiny. The union at Tai Yang capitalized on this international support and worked with Tai Yang management to build its own treatment facility. Faced with a contaminated local water supply, Tai Yang installed its own water filtration system, which gives employees convenient and unlimited access to clean, cool water. The centre builds and operates satellites, including the Hubble Space Telescope, for space science and earth science research. The centre also conducts significant amounts of research about the earth, the solar system and the cosmos. Workers are a mix of engineers, scientists, blue-collar workers and support staff. Water solution the United States Federal Government will not provide water coolers for its workers at most facilities under most circumstances. Federal regulations require only the provision of safe drinking water, and all government facilities have an ample supply of water fountains and, usually, kitchens with sinks. The justification for not providing water coolers is that federal facilities operate on taxpayers’ money and that taxes should not be used for luxury items. The Government will not pay for coffee, tea, doughnuts, sandwiches and many other fixtures of private company offices. The most 352 Clean drinking water common approach is a system in which 10 to 20 workers in a certain department or building wing pool their money to purchase 5-gallon (19-litre) bottles of water. Purchasing techniques vary but essentially rely on one worker with a pick-up truck or large car buying five or ten or more bottles at a time at a nearby wholesaler. These workers are then free to drink as much water as they please; there is no quota. Some are purchased with office budget or project budget money, as if it were a computer or carton of paper. Management orders this water, though, through a special procedure unavailable to other workers. Practical advice for implementation Water clubs are a way for employees to save some money on bottled water where employers are not willing to accommodate a request for water coolers. Confection et Emballages unfortunately burned down during the Haitian riots of 2004. Water solution Workers at Confection et Emballages worked in hot premises most of the year. The hot climate, together with the heat produced by the intensive lighting required for the special type of production, had a negative impact on the quality of the work environment. Structural works to address these deficiencies were considered too costly by the management, and improved mechanical ventilation only partially contributed to alleviate the problem. Seven water coolers served a workforce of 300 workers, one for every 40–45 workers, not an ideal ratio but certainly an improvement on the previous situation. Higher availability of water coolers in proximity to individual workplaces made their use very popular, and the management was in the process of introducing more of them to fully meet the demand. In the view of Sabrina St-Rémy, Production Planning and Control Manager, this cost was largely compensated by returns in performance by the workforce. Lack of water and consequent dehydration not only had serious effects on the health of the workers but also significantly lowered the level of attention and efficiency at work. Practical advice for implementation this was a simple, inexpensive solution in lieu of proper ventilation. Water treatment facilities usually use chlorine to kill harmful bacteria and other pathogens in the water supply; and chlorination is largely considered one of the greatest public health achievements of the twentieth century. Thus, bottled and filtered water is a benefit, not a necessity, at workplaces with a municipal water supply. Water coolers are standard in American offices and are gaining popularity elsewhere. Bottle-less solutions are filtration systems that remove chlorine and other chemicals from tap water.
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The other two mutations create a stop codon resulting in premature termination of translation and production of a truncated polypeptide purchase femara with american express menstrual cramps 7 days before period. Because nonsense mutations cause premature chain termination purchase femara with a visa menstrual record chart, the remaining polypeptide fragment is almost always nonfunctional cheap 2.5mg femara amex menstruation gift baskets. Hence, populations are usually highly polymorphic for the number of repeating units. Any short sequence repeated in tandem a number of times may gain or lose a few copies because of these types of errors, although the rate of change in the number of repeats depends, in some unknown manner, on the sequence in question as well as on its location in the genome. The umbrella term generally used to describe the processes leading to a change in the number of copies of a short repeating unit is replication slippage. One specific process that can result in such additions or deletions is unequal crossing-over, discussed in Chapter 7 (see Figure 7. The phenotypic consequences of insertion or deletion mutations depend on their location. When insertions or deletions happen in regulatory or coding regions, however, their effects may be significant. When they take place in coding regions, small insertions or deletions add or delete amino acids from the polypeptide, provided that the number of nucleotides added or deleted is an exact multiple of three (the length of a codon). Otherwise, the insertion or deletion shifts the phase in which the ribosome reads the triplet codons and, consequently, alters all of the amino acids downstream from the site of the mutation. Leu His Ala Ala Because of the frameshift, all the amino acids downstream from the insertion are different from the original. Any addition or deletion that is not a multiple of three nucleotides will produce a frameshift. Unless it is very near the carboxyl terminus of a protein, a frameshift mutation results in the synthesis of a nonfunctional protein. The structure and function of transposable elements were examined in Chapter 6 (eukaryotic transposable elements), Chapter 8 (prokaryotic transposable elements), and Chapter 9 (in connection with genetic engineering). For example, in some genes in Drosophila, approximately half of all spontaneous mutations that have visible phenotypic effects result from insertions of transposable elements. Among the ways in which transposable elements can cause mutations are the mechanisms illustrated in Figure 13. Most transposable elements are present in nonessential regions of the genome and usually do little or no harm. Because most transposable elements contain coding regions of their own, either transcription of the transposable element interferes with transcription of the gene into which it is inserted or transcription of the gene terminates within the transposable element. Even if transcription proceeds through the element, the phenotype will be mutant because the coding region then contains incorrect sequences. Another mechanism of transposable-element mutagenesis results from recombination (Figure 13. Transposable elements can be present in multiple copies, often with two or more in the same chromosome. Crossing-over takes place at the four-strand stage of meiosis (Chapter 4), but in parts B and C, only the two strands participating in the crossover are shown. Alternatively, the downstream element in one chromosome can pair with the upstream element in the homologous chromosome, diagrammed in Figure 13. An exchange within the paired elements results in one chromatid that is missing the region between the elements (right) and one chromatid in which the region is duplicated (left). However, every gene mutates spontaneously at a characteristic rate, so it is possible to assign probabilities to particular mutational events. Hence there is a definite probability that a specified gene will mutate in a particular cell and, likewise, a definite probability that a mutant allele of a specified gene will appear in a population of a designated size. The mutational process is also random in the sense that whether a particular mutation happens is unrelated to any adaptive advantage it may confer on the organism in its environment. A potentially favorable mutation does not arise because the organism has a need for it. The Nonadaptive Nature of Mutation the concept that mutations are spontaneous, statistically random events unrelated to adaptation was not widely accepted until the late 1940s. Before that time, it was believed that mutations occurred in bacterial populations in response to particular selective conditions. The basis for this belief was the observation that when antibiotic sensitive bacteria are spread on a solid growth medium containing the antibiotic, some colonies form that consist of cells having an inherited resistance to the drug. The initial interpretation of this observation (and similar ones) was that these adaptive variations were induced by the selective agent itself. Several types of experiments showed that adaptive mutations take place spontaneously and hence were present at low frequency in the bacterial population even before it was exposed to the antibiotic. One experiment utilized a technique developed by Joshua and Esther Lederberg called replica plating (Figure 13. After colonies have formed, a piece of sterile velvet mounted on a solid support is pressed onto the surface of the plate. Then the velvet is pressed onto the surface of fresh medium, transferring some of the cells from each colony, which give rise to new colonies that have positions identical with those on the first plate. A master plate containing about 107 cells growing on nonselective medium (lacking phage) was replica-plated onto a series of plates that had been spread with about 109 T1 phages. After incubation for a time sufficient for colony formation, a few colonies of phages-resistant bacteria appeared in the same positions on each of the selective replica plates. This meant that the T1-r cells that formed the colonies must have been transferred from corresponding positions on the master plate.