D. Warren Spence, MA

• Sleep and Alertness Clinic, University Health
• Network, Toronto, Ontario, Canada

Such approaches produce these intersectional subjects from which people can disavow their responsibility and implicated interface while maintaining that the representational mandate for diversity has been satisfied-in other words medicine 50 years ago order 100 mg solian with visa, a gestural intersectionality that can perform a citational practice of alliance without actually doing intersectional research or analyses medicine lookup order solian 50 mg without a prescription. More interesting to me is the question of what kinds of assemblages appear before and beyond intersectionality that might refuse to isolate trans and disability as separate and distinct conceptual entities treatment 5th metatarsal shaft fracture buy cheap solian 50mg on-line. What kinds of political and scholarly alliances might potentiate when each acknowledges and inhabits the more generalized conditions of the other treatment walking pneumonia purchase solian 50mg, creating genealogies that read both entities as implicated within the same assemblages of power rather than as intersecting at specific overlaps? The modern seeds of what Robert McRuer and Nicole Markotic (2012: 167) call ``crip nationalism' are evident here medicine 93 5298 cheap solian 100mg with amex, as the tolerance of the ``difference' of disability is negotiated through the disciplining of the body along other normative registers of sameness -in this case medications in checked baggage 50mg solian fast delivery, gender and sexuality. Part of the oscillation between intersectionality and assemblage is to methodologically move beyond the mutual interruptions of theory X by theory Y and vice versa. Such mutual interruptions are themselves symptoms of the liberal Downloaded from read. The focus here is not on epistemological correctives but ontological irreducibilities, irreducibilities that transform the fantasy of discreteness of categories not through their disruption but rather through their dissolution via multiplicity. For the latter question one could point to other endeavors at similar efforts to articulate trans as a force that impels indeterminate movement rather than as an identity that demands epistemological accountability or as a movement between identities. Susan Stryker, Paisley Currah, and Lisa Jean Moore (2008) explicate the ``trans-' (trans-hypen) in the sociopolitical; Jami Weinstein (2012) develops the notion of ``transgenre,' Mel Chen (2012) articulates trans as movements of speґ ciation. How might we assemble trans and disability such that rather than cohering as new transnormativities, they do not strive to manifest wholeness or to invest in the self as coherent and thereby reproduce liberal norms of being? Susan Stryker and Nikki Sullivan (2009: 61) argue that ``individual demands for bodily alteration are also, necessarily, demands for new forms of social relationality-new somatechnological assemblages that ethically refigure the relationship between individual corporealities and aggregate bodies. She is the author of Terrorist Assemblages: Homonationalism in Queer Times (2007). Definitions (a) Homosexuality and bisexuality For purposes of the definition of ``disability' in section 12102(2) of this title, homosexuality and bisexuality are not impairments and as such are not disabilities under this chapter. Accordingly, trans-as-error functions in tandem with rubrics of identificatory, mental, and bodily disorders that have historically included nonheterosexual identities and intersexed bodies. Benjamin Singer discusses in his work on photography, the medical gaze, and the trans-health model, trans as pathology -hence as an error to be corrected-has injurious ethical effects that usher in misunderstandings about nonnormatively embodied identities (2006: 602). By the late twentieth and twenty-first centuries, a range of trans identifications continue to be recognized via such notions of error, yet gender theorists and creative practitioners persist in reconceptualizing error as a mode of inhabitation and incorporation -so that ``error' ultimately describes the movement away from a normatively transcendent model of embodiment. In the Female Grotesque, Mary Russo writes of female bodies as constituted ``in error' and provides ways to think about the exclusions set up by feminist politics through a critique of social conformity (1995: 10­12). While the category of female has been associated with the grotesque other, so too have trans bodies become emblems of mutation and freakiness; but trans artists have, in the contemporary era, embraced such characterizations as an oppositional approach to inhabitation and cultural production. You must live the rest of your days entirely as a man, and you will only get more masculine with each passing year (2008) aggressively reroutes and displaces transphobic rhetoric designating transfemininities as bad copies of cis femininities by showing Downloaded from read. The association of ``error' with ``trans' therefore develops as a radically productive misalignment of the positive/negative binary required by contemporary queer politics of the body. Yetta Howard is an assistant professor in the Department of English and Comparative Literature at San Diego State University. She is completing a book, ``Ugly Differences,' and is at work on a new project called ``Erratic Erotics. Transgender raises questions about the relationship between ``sex' and gender role and identity, issues that have long been central to feminist thought. On a theoretical, political, and cultural level, however, feminist scholars have often been hostile to transgender practices (see, for example, Raymond 1980; Jeffreys 1997; Greer 1999). From this perspective, gender is seen as an expression of biological sex, with the categories of sex and gender codependent. Moreover, fuelled by the insistence that female biology or female socialization makes one a feminist, the place of trans people within feminist communities became disputed. In her seminal book Gender Trouble (1990), Judith Butler brought attention to how dominant understandings-including those of radical feminism-of sex, gender, and sexuality followed, and by turn reinforced, a ``heterosexual matrix. The emphasis on ``difference' within queer theory went beyond the prevailing notion of trans people as a homogenous group to recognize distinct trans identities and practices (Hines 2005). In viewing all gendered and sexual identities as socially constructed, queer theory aims to dissolve the naturalization and pathologization of perceived ``minority' identities. The writing of trans activists was central to challenging antitransgender feminism. For example, Sandy Stone (1996), Leslie Feinberg (1996), and Julia Serano (2007) offered explicit critiques of the rejection of trans people from feminism. Likewise, scholars working within the interdisciplinary area of transgender studies Downloaded from read. Henry Rubin, for example, argues for a dialectical rather than identity-based employment of embodiment to enable a feminist approach to take account of ``differently located bodies which appear similar in form' (Rubin 1996: 7­8). This approach has been incorporated into contemporary feminist and queer activist communities-often discussed as representing a ``third wave' of feminism- which are increasingly accepting of a multiplicity of gendered identities and representations that are not fixed to biological sex. Sally Hines is the director of the Centre for Interdisciplinary Gender Studies, University of Leeds. Her research interests are in the areas of gender, sexuality, intimacies, the body, citizenship, and recognition. Her latest book is Gender, Diversity, Citizenship, and Recognition: Towards a Politics of Difference (2013). This deceptively simple question has provoked heated discussion among festival programmers, film critics, and even filmmakers. Is a trans film one that features self-identified trans characters or characters that viewers would recognize as trans? Does it have to be meant for trans viewers, have a trans aesthetic, or just be open to trans interpretations? Who decides which of these criteria are important, in what contexts, and for what reasons? This last consideration -of the discourse around a film-is perhaps the most significant: when and why a film is talked about as a ``trans film' tells us a lot about the current state of representational politics and community reception as well as trends and directions in film criticism. The notion of trans cinema bears a similar sibling relation to that of queer cinema. Films that feature gender variance have always had a significant place in queer cinema, but considerations of trans issues have tended to be subsumed under the focus on sexuality. The recent emergence of transgender film festivals provides one corrective to this problem. Chen Kaige, 1993; see Leung 2010: 46) shows how film can spark rigorous discussion about the boundary and relation between queer and trans as interpretive categories. Critically Trans the growth of trans-centric approaches in film criticism has contributed to more diverse ways of ``seeing' trans on-screen. Analyses of stereotypes (Ryan 2009) expose the media dynamics that result in limiting and transphobic representations. Going beyond identity politics, adventurous critical approaches include the theorizing of transgender as a form of relationality between characters on-screen (Halberstam 2005: 92­96), the exploration of how cinema depicts bodily transformative procedures such as theatrical training and martial arts as forms of ``trans practice' (Leung 2010: 94­106), and the examination of cinematic affect and trans aesthetics (Steinbock 2011). While textual analyses dominate the field, there are also important recent efforts to conduct theoretically sophisticated and empirically grounded studies of trans audience and community reception (Williams 2012). Trans Auteurs On the production side, the most exciting development is an emergent wave of trans-identified filmmakers, most notably in North America, whose works are committed not only to telling stories meant consciously for a trans or transliterate audience but also to aesthetic and genre experimentation. These filmmakers are trans auteurs in the sense that they consciously construct a complex relation between their trans identification and their aesthetic signature on screen. Concerns have been expressed over the predominantly Western framework of trans studies that fails to account for forms of embodiment and identity that lie Downloaded from read. The same challenge faces the study of trans cinema: How should we approach films that feature gender variance in contexts outside or predating the Western discursive history of ``trans'? Should we speak instead of a kathoey cinema from Thailand that has produced such films as Iron Ladies (dir. How should we approach the genre of films featuring premodern forms of cross-dressed embodiment in traditional theaters across East Asia, such as Farewell My Concubine and the King and the Clown (dir. How do we speak of subjectivities that do not neatly differentiate between same-sex desire and cross-gender identification, like that of the protagonist in the Blossoming of Maximos Oliveros (dir. She is the author of Undercurrents: Queer Culture and Postcolonial Hong Kong (2008) and Farewell My Concubine: A Queer Film Classic (2010). The impact of transgender film festivals warrants more attention in film festival scholarship, which, as evidenced in a bibliography developed by the Film Festival Research Network (2013), is focused predominantly on queer film festivals. That is to say, it indexes a horizon of possibility already here, which struggles to make freedom flourish through a radical trans politics. Not only a defensive posture, it builds in the name of the undercommons a world beyond the world, lived as a dream of the good life. Or put another way, through its fetishistic attachment to the law and its vicissitudes, mainstream trans politics argues for inclusion in the same formations of death that have already claimed so many. This collusion can be seen in the lobbying for the addition of ``gender identity' to federal hate crimes enhancements. While the quotidian violence many trans people face-in particular trans women of color-is the material of daily life, this push for the expansion of the prison-industrial complex through hate crimes legislation proliferates violence under the name of safety. However, an ethic of gender self-determination helps us to resist reading these biopolitical shifts as victories. Here the state and its interlocutors, including at times trans studies, work to translate and in turn confine the excesses of gendered life into managed categories at the very moment of radical possibility. After all, the ``self ' in our contemporary moment points most easily toward the fiction of the fully possessed rights-bearing subject of Western modernity, the foil of the undercommons. However, here it is not the individual but a collective self, an ontological position always in relation to others and dialectically forged in otherness, that is animated. The negation of this collective self, as relational and nonmimetic, is the alibi for contemporary rights discourse, which argues that discrete legal judgments will necessarily produce progressive change. Antagonistic to such practices of constriction and universality, gender self-determination is affectively connected to the practices and theories of selfdetermination embodied by various and ongoing anticolonial, Black Power, and antiprison movements. For Frantz Fanon and many others, the violence of colonialism and antiblackness are so totalizing that ontology itself collapses; thus the claiming of a self fractures the everydayness of colonial domination. The Black Panther Party for Self Defense echoed a similar perspective in their 1966 Ten Point Plan. Self-determination, for the Panthers and for many others, is the potentiality of what gets called freedom. To center radical black, anticolonial, and prison abolitionist traditions is to already be inside trans politics. Gender self-determination opens up space for multiple embodiments and their expressions by collectivizing the struggle against both interpersonal and state violence. Further, it pushes us away from building a trans politics on the fulcrum Downloaded from read. As a nonprescriptive politics, its contours cannot always be known in advance-it is made and remade in the process of its actualization, in the time of resistance and in the place of pleasure. Becoming, then, as Gilles Deleuze might have it-or more importantly, as Miss Major lives it (Stanley and Smith 2011)-is the moment of gender selfdetermination: becoming liberated as we speak. Eric is an editor of Captive Genders: Trans Embodiment and the Prison Industrial Complex (2011) and has published articles in Social Text, Women and Performance, and American Quarterly. The ``Posttranssexual Manifesto' asserts that the essence of posttranssexuality is subversion. We operate by undermining essentialist feminist discourses that reify binarism under other names, and the author asks the trans community to take up arms in that effort by asserting the primacy of selfdeclaration-by ``reading oneself aloud. The meta of that description could well be an operational definition of post-posttranssexuality: asserting the vision that guides our acts and drives us forward, while simultaneously refusing closure on any single discourse of our own manifold discourses that, in their enticing collisions and rebounds and fungible resonances, constitute, somewhere near their center of mass, the presumptive subject of this journal. Keep in mind that no one working in transgender studies has a degree in transgender studies. The value in that particular fact for us is that trans studies is still coalescing. But soon enough we will, as surely as the night follows the day, and you can count on that. In Phase One, individuals, geographically scattered and usually unaware of each other, generate the rough ideas of what will become the discipline. In Phase Three, a few people with the necessary energy and drive come together, geographically or, as is more usual, virtually, and organize the first publications, meetings, and, later, conferences. This is the point when the larger, nascent protocommunity first begins to become self-aware and when the loose constellation of ideas that gravitate around this not-quite-existent collection of individuals begins to take shape. In Phase Four, the general description and usually the name of the discourse achieve a level of acceptance among ``TradAcs' (traditional academics). Aside from its indexicality in simultaneously defining and calling into being a sociopolitical class, transgender-a word that has existed for less than twenty years - still, and with great immediacy, evokes fungibility and transgression; the irruption of the trans episteme into the smooth fabric of sociality and theory, still fresh as it is, possesses enormous power for positive change. Studies is an institutional concept, meant in part to maintain a certain distance between observer and observed, to preserve objectivity -or, at minimum, to afford plausible deniability. Yet we have barely begun, really, to explore how powerful trans-born in the joy and pain of living bodies and fully engaged in the world-can be. Dulce et decorum est: ``sweet and fitting it is,'1 this moment when our feisty, nasty selves, saturated with change and flushed with success, meet the institutional rewards and requirements of transitioning from a movement to a discipline. My stakes in our nascent community, and in writing this, are, long after transgender studies has become an academic commodity, to encourage us to keep thinking like revolutionaries. From its oldest foundations, the present-day academy is designed to be terminally conservative, and it carries out that mission by creating future academics in its image. By virtue of this very narrow slice of time in which we now exist and work, we have so far avoided being digested by some academic institution and turned into its own flesh. If you do nothing else, ever, than survive the struggle to find your own voice, you have still fulfilled a primal life goal, and everything else that happens flows from that pluripotent act. Finding your voice is the deeper meaning underlying the hoary mythoids that saturate Western storytelling. Eventually there are balances and inflection points to be found between speaking and being spoken, because in living fully in the world one does both; but at the inception, stick with speaking. If you speak from your heart about what really matters to you, then the work and your love for it will follow. It is extremely important-crucial-that from the very beginning your work flows from your own stakes in the discourse. But speaking for myself, ``change the world' is not just bloviation; I do really believe that if we do not think in those terms, we are not doing our job.

In this case symptoms 9 weeks pregnancy order solian 100mg on-line, the partial agonist is able to produce only 60% of the maximal response symptoms 8 days before period buy solian 50 mg cheap. Potency is often expressed as the dose of a drug required to achieve 50% of the desired therapeutic effect medicine you can order online safe solian 50mg. A drug with a higher therapeutic index is safer than one with a lower therapeutic index medicine 4h2 solian 100mg overnight delivery. The therapeutic window is the range of plasma concentrations of a drug that will elicit the desired response in a population of patients medicine look up drugs buy solian 50mg online. The antagonist can block the effect of an agonist or it can reverse the effect of an agonist symptoms 5 days past ovulation generic solian 100mg on line. Naloxone has no effect of its own but will completely reverse the effects of any opioid agonist that has been administered. Competitive antagonists make the agonist look less potent by shifting the dose response curve to the right. Because the antagonists theoretically have no effect of their own, we need to consider their effect on the agonist. In the graph in Figure 2­4, we determined the biological effect produced by a series of concentrations of agonist. We then repeat the same experiment in the presence of a fixed concentration of an antagonist. When the effect of the agonist is tested in the presence of a fixed concentration of a competitive antagonist, the agonist appears less potent. These antagonists are competitive; that is, they compete for the same site on the receptor that the agonist wants. As we increase the concentration of agonist, we increase the odds that an agonist molecule will win the receptor spot and produce an effect. A noncompetitive antagonist reduces the maximal response that an agonist can produce. We first determine the biological effect produced by increasing concentrations of an agonist. We repeat these measurements in the presence of a fixed concentration of a noncompetitive antagonist (Figure 2­5). Therefore, the maximal biological response produced by the agonist appears to have decreased because of our addition of the noncompetitive antagonist. Then the activity of the agonist is tested in the presence of a fixed concentration of noncompetitive antagonist. They can irreversibly bind to the receptor so that the agonist cannot be competed off, they can bind to a site different from the agonist and either prevent agonist binding or prevent the agonist effect. Some books will use different terminology, such as uncompetitive, for the different mechanisms. They are not the same as antagonists, which block the effects of both agonists and inverse agonists. Originally, it was used to describe the action of some drugs on conductance through ligand-gated ion channels. Agonsts will increase the relative amount of time the channel is in the open state compared to the basal rate. Inverse agonists will decrease the amount of time the channel is open compared to the basal rate. An inverse agonist will decrease the amount of chloride that moves into the neuron, which will result in a depolarization compared to the resting state. Current theory states that G protein­coupled receptors are in an equilibrium between an active and inactive state. Inverse agonists bind to the receptor and tip the equilibrium toward the inactive state, while agonists bind the receptor and tip the equilibrium toward the active state. For there to be inverse agonist in a receptor system, there must be activity in the basal, resting state in the absence of any ligand. While the net physiological result of giving an inverse agonist and an antagonist may be the same, the molecular mechanism is not. They do, however, block the effects of both the agonists and inverse agonists (Figure 2­6). Use this example to remember that weak acids donate a hydrogen ion and become charged. If we decrease the pH by adding more H+, we will drive the equilibrium for the weak acid more to the left, which is the nonionized (uncharged) form. If we take away H+, making the pH higher, we will drive the equilibrium toward the right. This increases the concentration of the ionized form of the weak acid (Figure 3­1). When the pH is higher than the pK for the acid, the charged form of the acid predominates. For a weak base, when the pH is less than the pK, the ionized form (protonated) predominates. When the pH is greater than the pK, the unprotonated (nonionized) form predominates. Removing H+ to raise the pH will drive the equilibrium to the left toward the uncharged form (unprotonated) of the base (Figure 3­2). Answers: (1) a weak base; (2) higher, because more weak acid will be ionized the more the pH exceeds the pK. In the case of hypothetical Newdrug, you discover that some of the drug is inactivated by the acid in the stomach. You redesign the pill with a coating that is stable in acid but dissolves in the more basic pH of the small intestine. In this graph, an orally administered drug is compared with the same drug administered intravenously. It is defined as the volume of plasma from which all drug is removed in a given time. At the end of the first hour, 1000 mg of crud has been removed from the aquarium (1000 mL of 1 mg/mL). It would take 10 hours (10 L at 1 L/h) if the clean water was pumped into another container. In the case of clearance in the aquarium, however, the clean water is returned to the tank and dilutes the remaining crud (Figure 3­4). The pump cleans a fixed amount of water in the aquarium in a set amount of time (the clearance). A more official definition is the following equation: C Clearance = R Rate of removal of drug (mg/min) a r Plasma concentration of drug (mg/min) r Notice that this equation gives you units of milliliters per minute (mL/min) or volume per unit time. Total body clearance is the sum of the clearances from the various organs involved in drug metabolism and elimination. It assumes that a drug is evenly distributed and that metabolism or elimination has not taken place. From this finding you can calculate the volume of water in which the sugar was dissolved, as follows: 1 mg/mL = 1000 mg/volume of water thus, Volume = 1000 mg =1000 mL 1 mg/mL In this case the volume was 1000 mL or 1 L. The only explanation is that the drug is hiding someplace in the body where it is not recorded by the measurement of plasma concentration. The drug could be lipid soluble and stored in fat, or it could be bound to plasma proteins. As this example shows, the volume of distribution is a hypothetical volume and not a real volume. The volume of distribution gives a rough accounting of where a drug goes in the body, especially if you have a feel for the various body fluid compartments and their sizes (Figure 4­1). In addition, it can be used to calculate the dose of a drug needed to achieve a desired plasma concentration. Most drugs disappear from plasma by processes that are concentration-dependent, which results in first-order kinetics. With first-order elimination, a constant percentage of the drug is lost per unit time. On the log plot (Figure 4­2), the curve is linear and the slope of the line is equal to ke/2. The half-life (t1/2) is the period of time required for the concentration of a drug to decrease by one half. On the left, the y-axis is a linear scale, while on the right, the y-axis is a logarithmic scale. The half-life is constant and related to ke for drugs that have first-order kinetics. The time it takes for the concentration to decrease by 50% is indicated in two places on the curve. Metabolism in the liver, which involves specific enzymes, is one of the most important factors that contribute to a drug having zero-order kinetics. The most common examples of drugs that have zero-order kinetics are aspirin, phenytoin, and ethanol. For drugs with zero-order kinetics, a constant amount of drug is lost per unit time. The half-life is not constant for zero-order reactions, but depends on the concentration. Because the t1/2 changes as the drug concentration declines, the zero-order t1/2 has little practical significance. On the left, the drug concentration is plotted on a linear scale and on the right, on a logarithmic scale. Notice that drugs with zero-order kinetics show a straight line on the linear scale. The term dose-dependent refers to drugs that are first-order at lower doses and switch to zero-order at higher doses (often in the therapeutic range). Nonlinear refers to the fact that drugs with zero-order kinetics do not show a linear relationship between drug dose and plasma concentration. The plasma concentration at this point is called the steady-state concentration (Css). When a drug is given as a continuous infusion it will increase in concentration in the blood until the rate of elimination is equal to the infusion rate. The plasma concentration at this point is called the concentration at steady state, or Css (Figure 4­5). When the amount delivered in a unit of time is equal to the amount eliminated in the same time unit, the plasma concentration is said to have reached steady state. At first the plasma level will be low and the infusion rate will be greater than the elimination rate. Remember that the elimination rate is proportional to the plasma concentration of the drug, so as the concentration rises so does the elimination rate. As the elimination rate increases with the increasing plasma concentration, the rate of increase in the plasma level will slow. With multiple dosing schedules, we normally assume that early doses of the drug do not affect the pharmacokinetics of subsequent doses. With repeated dosing the concentration fluctuates around a mean (steadystate value) with peak and trough values. Here, steady state is achieved when the dose administered and the amount eliminated in a given dosing interval is the same (Figure 4­6). The goal is to have the concentration remain within the therapeutic window, where it is effective, but not toxic. Either the peak reaches into the toxic range, in which case the patient experiences side effects, or the trough drops too low and the drug is no longer effective. Plasma concentration Css Peak Trough Dose Dose Time this graph shows the change in concentration with repeated doses. Peak and trough levels are indicated, as well as the steady-state concentration (or average concentration). There is a good bit of math behind these numbers, which you can read about elsewhere if you want. The bottom line is that during each half-life, 50% of the change from the starting point to Css is achieved. In the next half-life, we will gain 50% of this remaining distance, or 1/2 of 50%, which is 25%. A loading dose is a single large dose of a drug that is used to raise the plasma concentration to a therapeutic level more quickly than would occur through repeated smaller doses. A single dose of a drug can be given that will result in the desired plasma concentration. This dose is called a loading dose if followed by repeated doses or a continuous infusion that will maintain the plasma concentration at the desired level (termed maintenance doses). As you can see in Figure 4­7, as the concentration begins to decline after the loading dose, the concentration contributed by the continuous infusion begins to increase. Notice how quickly the plasma concentration reaches the steady-state concentration with this technique. The goal of metabolism is to produce metabolites that are polar, or charged, and can be eliminated by the kidney. There are a whole series of cytochrome P-450 enzymes that can be inhibited or induced. Be aware of the potential problem and learn the most commonly interacting drugs as you gain experience. These combine a glucuronic acid, sulfuric acid, acetic acid, or an amino acid with the drug molecule to make it more polar.

It might be better to defer attempts to resolve -theoretically or politically -the messiness in order to understand what a particular system of sex designation does for a particular state project such as recognition or redistribution (Currah symptoms of high blood pressure discount solian 50 mg on line, forthcoming) symptoms queasy stomach 100 mg solian with visa. Of course treatment of hyperkalemia 50 mg solian amex, states should not only or always be imagined as messy medications such as seasonale are designed to 100 mg solian for sale, scattered nodes of local and arbitrary power arrangements symptoms enlarged prostate purchase 50 mg solian overnight delivery. For this purpose medicine daughter lyrics cheap 100 mg solian mastercard, the most apt definition of the state begins with the simple description from Max Weber: ``A human community that (successfully) claims the monopoly of the legitimate physical violence within a particular given territory' (1991: 78). Still, much of what states do-regulating the health, safety, and public welfare through myriad regulations, rules, decisions, practices - does not reach the threshold of juridical violence, even if those actions are ultimately undergirded by its threat. While it is crucial to theorize the singular finality of state violence, neglecting to examine the messiness of actually existing and potentially incommensurate policies, practices, rules, and norms risks substituting the conceptual for the concrete and gets in the way of understanding what might actually be going on (Latour 1995: 48). His recent publications include ``Homonationalism, State Rationalities, and Sex Contradictions' (Theory and Event, 2013) and ``Securitizing Gender: Identity, Biometrics, and Gender Non-conforming Bodies at the Airport,' coauthored with Tara Mulqueen (Social Research, summer 2011). Gramsci used the term to designate proletarian and peasant classes denied access to political representation or voice within government by the fascist Italian state. More broadly, Gramsci (1971) used the term to designate classes excluded from political hegemony by ruling elites. Postcolonial critic Gayatri Chakravorty Spivak reframed the term to foreground gendered, caste, class, and colonial constitutive elements barring the Downloaded from read. Troubling what might be seen, in the work of the Subaltern Studies Group, as the essentializing of the subaltern as a specific population, Spivak located the subaltern at the interstices of competing or conflicting discursive formations striated by class differentiation (1987). She argued that between the competing discursive claims of an imperial Western feminism and an anticolonial and sexist Hindu nationalism, the subjective and speaking position of a resistant Hindu woman was barred (1988). She reiterated that the subaltern may be silenced by ``her own more emancipated granddaughters: a new mainstream. There are several senses in which the term subaltern speaks to and within trans studies. These conventions required ``prospective transsexuals' to signify as highly gender normative within their sex of identification, as intensely body dysphoric, and as heterosexual. Meyerowitz (2002), Jay Prosser (1998), Henry Rubin (2003), and others have documented transsexual agency in forging diagnostic criteria as a way of securing access to transition-related healthcare, the erasures and coercive productivities of the diagnosis subalterned both transsexual and nontranssexual transgender subjects, subjecting both to institutional regulation and administrative violence. The meaning and political valences of such woodworking are, however, contested in queer, feminist, and trans studies. In Changing Sex, Bernice Hausman (1995) draws upon Michel Foucault to propose that transsexual subjects speak only through the demand for surgery and are duped into reproducing Downloaded from read. For Hausman, trans subjects are less excluded from meaningful speech than definitively constructed by hegemonic articulations. However, Prosser argues that Hausman obscures her own gendered embodiment and subjective investments to tacitly justify her nontranssexual authorial location as ``the authoritative site from which to speak' (Prosser 1998: 132­33). Indeed, Viviane Namaste (2000, 2005), Prosser (1998), and Rubin (2003) all challenge queer feminist deployments of poststructuralism that mobilize transgender figures in the service of theoretical projects that paradoxically deny transsexual experience and speech. Demonstrating the exclusion of sex workers, prisoners, substance users, the poor, the racialized, and nonstatus people, Aizura (2011), Namaste (2000, 2005), Ross (2005), and Spade (2011) expose practices of erasure (of the excluded subaltern) in the contemporary production of the rights-bearing transgender subject. Subaltern trans positions also appear at the interstice of transnational sexualities and genders, modernization and globalization, and through the networks of global gay human rights discourse and Anglo-American transgender liberation. How these English language forms encounter, appropriate, or are translated by globally local ``trans' constituencies raises questions of the political economy of identity movements and discourses. Meanwhile, Katrina Roen (2001) queries how, within capitalist globalization, transgender and transsexual rhetorics are valued as modern and metropolitan in opposition to non-Western and indigenous gender-variant identities. Conversely, genderqueer and transgender writers contest the terms of inscription within medically sanctioned transsexual discourses, arguing that they produce hierarchies of authenticity, reproduce class- and race-based privilege, and require that gender-nonconforming subjects enlist within binary gendered positions to be recognized (Halberstam 1998, Wilchins 2002). Such traces of ``border wars' attest to the violence by which transsexuality, transgenderism, and other kinds of gender and sex variance are repeatedly buried or erased from the social world. Her recent publications include ``Notes towards Thinking Transsexual Institutional Poetics' in Trans/acting Culture, Writing, and Memory: Essays in Honour of Barbara Godard (2013), Wanting in Arabic: Poems& (2nd ed. Herculine Barbin: Being the Recently Discovered Memoirs of a NineteenthCentury Hermaphrodite. Sex Change, Social Change: Reflections on Identity, Institutions, and Imperialism. An Ethics of Dissensus: Postmodernity, Feminism, and the Politics of Radical Democracy. Surgery has been an important part of trans agency and medical transitioning since Michael Dhillon began the first of thirteen operations to reconstruct his morphological sex in 1946. The desire for surgery not only became a definitive characteristic of transsexuality, distinguishing it from other so-called disorders like cross-dressing, transvestism, and homosexuality. But it was also narrowly conceived as the reconstruction of morphological sex, which excluded trans people who wanted to keep their genitals intact from treatment. Many trans people began having surgeries to masculinize or feminize parts of their body while leaving their genitalia intact. In turn, this helped produce a proliferation of transition trajectories in a multitude of directions, enabling (in part) the emergence of a critical transgender movement in the 1990s and debunking clinical assumptions that binary gender was the end goal of transitioning. A ``somatechnology' perspective views trans surgery as part of a larger techne of discursive and institutional practices (law, medicine/science, art, education, information and surveillance technologies) through which trans bodies are constituted, positioned, and lived. While the former perspective sheds important light on somatechniques of trans identities, the emphasis is nonetheless on how trans bodies/identities are affected by discursive and nondiscursive practices. Equally important is understanding how trans people affect the evolution of discourses and technologies through individual/personal as well as collective resistance, organization, and struggle. Yet it was not until a transsexual man, Dhillon, contacted him that Gillies realized the more extensive potential of his surgical technique to assist not only cisgender but also transsexual males. Cutting, splicing, pulling, tucking, and transplanting nerves, arteries, blood vessels, skin, fat, and muscle tissues, trans surgeries rewrite the functional and phenomenological circuitry of human bodies and change how subjects experience and express gender and sexuality. In doing so, trans bodies not only rewrite normative scripts of binary sex and gender. They are also (re)writing medical knowledge of human bodies and surgical practice, as surgeons, spurred by the needs of their patients, continue experimenting with new technologies and practices to produce better results. Surgery gives fleshly form to proprioceptive gender, bringing bodily matter into alignment with gender self-image, and allows trans people new embodiments of experiencing/expressing gender and sexuality that were not possible before surgery. Trans people suffer discrimination, abuse, and even death when their morphological sex is discovered to be different from their visible gender. Depending on the context, for example, genital surgery might prevent trans women from being sentenced to male prisons where they would likely be sexually harassed and assaulted on a daily basis. Surgery can also remove barriers of exclusion from certain gender-specific spaces. While sex reassignment surgery can function as a vehicle of trans agency, it can also be deployed to police nonnormative trans bodies that transgress and challenge gender and sexual normativity. This is most evident in social policies requiring sex reassignment surgery for a legal change of sex on identification documents, for example, or bureaucratic rules making sterilization mandatory for gender transitioning. A biopolitical analysis emphasizes how these mandates are part of a larger administrative apparatus of managing bodies and their productive and reproductive capacities for state interests. Pregnant men, men with breasts, and females with penises all unhinge the sex/gender binary and heterosexuality as socially engineered contrivances, while bureaucracies are erected to reel these transgressive bodies back in for biopolitical management. Despite the attempt at containing trans bodies, many people still find ways (depending on their economic and political situation) to circumvent the system and exercise some modicum of control of their transition trajectory. Cotten is an associate professor of gender studies at California State University, Stanislaus. His areas of research are in transgender surgery and medicine and transgender identities in Africa and the Diaspora. His latest book is Hung Jury: Testimonies of Genital Surgery by Transsexual Men (2012). Following these guidelines, medical professionals approved surgery or hormones for clients fitting the standardized criteria and expected these clients to eventually eliminate all references to their former gendered lives and fully assimilate into a normatively gendered world (see Stone 1991; Califia 2003). Thus two major forms of surveillance operate through medical and psychiatric institutions: first, the monitoring of individuals in terms of their ability to conform to a particular medicalized understanding of transgender identity; and second, the expectation that medical transition should enable those individuals to withstand any scrutiny that would reveal their transgender status. These forms of surveillance also reach beyond medical contexts to influence law, policy, and social relations. For instance, legal changes of gender on identification documents typically rely on medical evidence as proof of gender identity, and the data collected as part of these legal processes (along with any form requiring one to identify as a specific gender) form a paper trail through which state agencies may track, assess, and manage transgender people. Similarly, the policing of gendered spaces ranging from public bathrooms to homeless shelters disproportionately affects gender-nonconforming people (Spade 2011). And representations of transgender people in popular media such as police dramas and daytime talk shows often encourage viewers to uncover gendered truths by scrutinizing certain bodies and identities. All of these practices reinforce the discursive and material links between the category transgender and various forms of surveillance, from the systemic to the quotidian. But transgender people, particularly trans people of color, poor trans people, trans youth, and trans immigrants, are especially targeted by such scrutiny because they are more likely to have inconsistent identification documents. Related security measures, including increased restrictions on immigration and asylum, new forms of state scrutiny of those perceived to be undocumented immigrants, and the implementation of x-ray scanning technologies in airports and prisons typically do not cite explicit concerns with transgender populations. But because these policing practices are often concerned with individuals who appear to be fraudulent or deceptive, gender-nonconforming people-culturally constructed as concealing something-disproportionately feel their effects. Even while surveillance mechanisms discipline transgender people, the very efforts made to police and manage gender nonconformity reveal productive contradictions and fissures in surveillance practices. By seemingly displacing gender regulation onto only transgender people, nontransgender bodies and identities appear both naturally gender normative and free from scrutiny. Yet the difficulty these systems encounter in trying to classify gender-nonconforming people demonstrates how regulatory norms of gender affect all bodies and identities by enforcing categories that are made to seem natural. Standards of Care: the Hormonal and Surgical Sex Reassignment of Gender Dysphoric Persons. Symbolic violence refers to the almost unconscious, internalized modes of cultural of social domination (Bourdieu 1991). Heteronormativity refers to a system in which sexual conduct and kinship relations are organized in such a way that a specific form of heterosexuality becomes the culturally accepted ``natural' order. Thus biological sex, sexuality, gender identity and expression and normative gender roles are aligned in such a way that a dominant view on sexual and gender relations, identities, and expressions is produced. The forms of resistance to the effects of heteronormativity can likewise be located on a sliding scale of subversion. The forms of subversion range from struggles for sexual rights (political struggles for legal reform and social policies) to material (economic) resistance and to symbolic forms of subversion. Symbolic subversion extends from self-defeating strategies, via various forms of adaptation, to more or less public forms of rebellion. Just as cultural and religious norms determine the particular construct of heteronormativity in a given society, they also shape the salience of particular types of resistance and make certain forms of subversion intelligible. Subversions may be divided into manifest rebellions and symbolic forms of subversion; the latter range from self-defeating yet defiant actions of (self) destruction to ostensible adaptations to the current heteronormative model. Open, physical, and visible struggles include outright rejection of the model and the claims of sexual agency and citizenship. In situations where transgender people are stigmatized, lonely, and legally, economically, and psychologically vulnerable, searches for economic stability, social respect, friendship, and/or sexual partners constitute forms of symbolic subversion of the dominant gender order. Even if they ostensibly or publicly accept its hegemony, their very actions and search for accommodation within the system reveal subversion, or what James C. Scott (1990: 137) referred to as the ``hidden transcripts, the disguised ideological resistance' to the dominant order. Symbolic subversion can be seen as a continuum, its form ranging from outright resistance to (partial) compliance and even to defiant defeat. In the case of a double suicide of a lesbian couple, when they publicly go to their death together, usually because they are denied the possibility of staying together, the ultimate unmasking of heteronormativity is acted out. The myth of the ``harmonious patriarchal family' is uncovered for what it means to those who are unable to live by its norms: a cruel power ploy that may end in death for those who experience this form of ``happiness' as a travesty of the bliss they had found for themselves. Some transgender people may perform their masculinity or femininity so convincingly that they are seen to be ``normal' men or women, which is often also how they prefer to see themselves. Others are more likely to be perceived as rupturing the sex-gender nexus and subverting heteronormative norms, even though they may embrace certain aspects of them. The subversion of heteronormativity covers a wide range from open forms of defiance and rebellion to more covert methods, rooted in daily practices and more or less subconscious strategies for survival. A certain amount of defiance is needed to survive -socially, economically, emotionally, and even physically. Subversion should be seen as a continuum of practices and motivations-from visible, physical forms of resistance to more invisible, symbolic forms. Tatume addresses my location on Cayuga Nation Territory, one of the Six Nations of the Haudenosaunee, as central to what it means to me to be a diaspora Boricua queer, trans-/gender-nonconforming in this queer decolonial time and Indigenous place (Halberstam 2005). The intersections of diaspora and decolonization are what I attempt to trans - through a juxtaposing of the vocabulary of growing tatume and the challenges of definition it poses within a binary view of growing seasons and the concepts of immature (summer squash) and mature (winter squash). One of the earliest references to squash, in English, that I could locate is attributed to R. Squash is one of ``The Three Sisters' (squash, corn, and beans) planted together by the Haudenosaunee. The practice of interplanting, for example, the Three Sisters is a fundamental indigenous growing practice. To plant only one crop, to genetically engineer seeds to grow the sweetest vegetable, to create a tomato that can be picked green and shipped thousands of miles, is the continued imperialism of the fifteenth century; we are not postcolonial. Genetic modification is sold through the ideology of feeding the world; saving the hungry. But in fact, indigenous cultural property is stolen through the process of patenting. Traditional Ecoloґ gical Knowledge (Salmon 2012: 82) is patented through a process of biocolonialism (Howard 2001). The ideology of saving the other fuels a colonizing mission that has not stopped (Smith 2012). To understand tatume-and the vocabulary that surrounds its Western explanations-is to confront colonization and the struggle for land.

Curiously treatment zygomycetes purchase solian 100mg free shipping, it is energetically more favorable for the cell to produce many foldings and then edit the protein repertoire than to produce only a single correct conformation treatment jock itch generic solian 50 mg without prescription. Molecular chaperones associate with polypeptides in the endoplasmic reticulum and promote correct folding treatment of uti buy solian 100 mg overnight delivery, after which they dissociate from those proteins that have assumed the correct conformation treatment neuroleptic malignant syndrome discount 100mg solian visa. By contrast symptoms 6dpo solian 100 mg fast delivery, incorrectly folded proteins remain bound to their chaperones and are subsequently degraded by the ubiquitin­proteasome system (see above) treatment yeast uti cheap solian 50 mg amex. Evolutionary preference for energy conservation has dictated that a substantial proportion of newly formed proteins are rogues unsuitable for the society of civilized cells. The protein does not reach its destination at the cell membrane, leading to a defect in chloride transport that produces the disease cystic fibrosis. Thus, particularly in nondividing cells, age-related impairment of cellular antioxidant defenses leads to protein oxidation, which commonly alters protein tertiary structure, exposing interior hydrophobic amino acids that are normally hidden. In situations of mild to moderate oxidative stress, 20S proteasomes recognize the exposed hydrophobic moieties and degrade these proteins. However if oxidative stress is severe, these proteins aggregate by virtue of a combination of hydrophobic and ionic bonds. Whether or not the proteins contained in the aggregates are ubiquitinated, the aggregates are indigestible. Any Ub bound to them is lost, which may cause a cellular deficit in Ub and impair protein degradation in general. Failure to secrete this antiprotease into the circulation also leads to unregulated proteolysis of connective tissue in the lung and loss of pulmonary elasticity (emphysema). These abnormal proteins often form insoluble aggregates, which may be visualized as extracellular deposits, the appearance depending upon the specific disease. These accumulations often assume the forms of various types of amyloid and produce cell injury in systemic amyloidoses (see Chapter 23) and a variety of neurodegenerative diseases (see Chapter 28). Lipofuscin Numerous hereditary and acquired diseases are caused by evasion of the quality control system designed to promote correct folding and eliminate faulty proteins. For example, some Lipofuscin is a mixture of lipids and proteins containing a golden-brown pigment called ceroid. Lipofuscin tends to accumulate by accretion of oxidized, cross-linked proteins (see. It occurs mainly in terminally differentiated cells (neurons and cardiac myocytes) or in cells that cycle infrequently (hepatocytes) (see. Although it was previously thought to be benign, there is increasing evidence that lipofuscin may be both a result and a cause of increasing oxidant stress in cells. Differential handling of protein that is correctly folded (left arrows) and protein that is incorrectly folded (right arrows). Correctly folded proteins are chaperoned from the ribosomes that produce them to their ultimate cellular destination. Incorrectly folded proteins bind to ubiquitin, an association that directs the protein to proteasomes, where the misfolded protein is degraded. Melanin Melanin is an insoluble, brown-black pigment found principally in the epidermal cells of the skin, but also in the eye and other organs (see. It is located in intracellular organelles known as melanosomes and results from the polymerization of certain oxidation products of tyrosine. The amount of melanin is responsible for the differences in skin color among the various races, as well as the color of the eyes. The hereditary inability to produce melanin results in the disorder known as albinism. The presence of melanin is also a marker of the cancer that arises from melanocytes (melanoma). Exogenous Pigments the indigestible material is stored indefinitely within macrophages. Although the gross appearance of the lungs of persons with anthracosis may be alarming, the condition is innocuous. Tattoos are the result of the introduction of insoluble metallic and vegetable pigments into the skin, where they are engulfed by dermal macrophages and persist for a lifetime. Iron and Other Metals Anthracosis refers to the storage of carbon particles in the lung and regional lymph nodes (see. Virtually all urban dwellers inhale particulates of organic carbon generated by the burning of fossil fuels. The liver and bone marrow are particularly rich in ferritin, although it is present in virtually all cells. Hemosiderin is a partially denatured form of ferritin that aggregates easily and is recognized microscopically as yellow-brown granules in the cytoplasm. Normally, hemosiderin is found mainly in the spleen, bone marrow, and Kupffer cells of the liver. Total body iron may be increased by enhanced intestinal iron absorption, as in some anemias, or by administration of ironcontaining erythrocytes in a transfusion. In either case, the excess iron is stored intracellularly as ferritin and hemosiderin. In this condition, iron is present not only in the organs in which it is normally found but also throughout the body, in such places as the skin, pancreas, heart, kidneys, and endocrine organs. The pulmonary siderosis encountered among certain metal polishers is accompanied by increased risk of lung cancer. Excess accumulation of lead, particularly in children, causes mental retardation and anemia. In Wilson disease, a hereditary disorder of copper metabolism, storage of excess copper in the liver and brain may lead to severe chronic disease of those organs. Ischemia/Reperfusion Injury Reflects Oxidative Stress C=O Unfolded protein carbonyl Aggregation Binds 20S proteasome Cross linking Degradation Ub Ub Propagation Ischemia/reperfusion (I/R) injury is a common clinical problem that arises in occlusive cardiovascular disease, infection, shock, and many other settings. I/R injury reflects the interplay of transient ischemia, consequent tissue damage, and exposure of damaged tissue to the oxygen that arrives when blood flow is reestablished (reperfusion). Xanthine Oxidase Xanthine dehydrogenase may be converted by proteolysis during a period of ischemia into xanthine oxidase. This enzyme requires oxygen to catalyze the formation of uric acid; activated oxygen species are byproducts of this reaction. This forces a change in protein tertiary structure, exposing hydrophobic residues ordinarily on the protein interior. These protein carbonyls may be eliminated by 20S proteasomes without ubiquitination or, especially if the oxidant stress is heavy, they may aggregate on the basis of hydrophobic interactions. Some aggregated proteins may be ubiquitinated, but such aggregates cannot be degraded. With further accretion, aggregate substituents undergo crosslinking and continue to enlarge. Alterations in the cell surface that occur during ischemia and on reperfusion induce the adhesion and activation of circulating neutrophils. These cells release large quantities of activated oxygen species and hydrolytic enzymes, both of which may injure the previously ischemic cells. Recruitment of these inflammatory cells to affected areas increases local production of oxygen free radicals. However, if the increase in total body iron is extreme; we speak of iron overload syndromes (see Chapter 14), in which iron deposition is so severe that it damages vital organs-the heart, liver, and pancreas. Severe iron overload can result from a genetic abnormality in iron absorption, hereditary hemochromatosis (see. Alternatively, severe iron overload may occur after multiple blood transfusions, such as in treating hemophilia or certain hereditary anemias. Nitric oxide dilates the microvasculature by relaxing smooth muscle, inhibits platelet aggregation, and decreases adhesion between leukocytes and the endothelial surface. Photomicrograph of the liver from an 80-year-old man shows golden cytoplasmic granules, which represent lysosomal storage of lipofuscin. A mediastinal lymph node, which drains the lungs, exhibits numerous macrophages that contain black anthracotic (carbon) pigment. Prussian blue stain of the liver reveals large deposits of iron within hepatocellular lysosomes. Inflammatory Cytokines Ionizing Radiation 300-1000 R >2000 R Radiolysis of H2O Energy transfer to macromolecules I/R injury leads to the release of cytokines that (1) promote vasoconstriction, (2) stimulate the adherence of inflammatory cells and platelets to endothelium, and (3) have effects at sites distant from the ischemic insult itself. This cytokine is also responsible for increases in neutrophil trafficking and neutrophil-related damage at locations distant from the site of I/R injury itself, thereby causing systemic effects. In addition, augmented release of endothelin during I/R injury promotes the adherence of inflammatory cells and increases vascular tone and permeability. We can put reperfusion injury in perspective by emphasizing that there are three different degrees of cell injury, depending on the duration of the ischemia: · With short periods of ischemia, reperfusion (and, therefore, the resupply of oxygen) completely restores the structural and functional integrity of the cell. In this case, cell damage does not depend on the formation of activated oxygen species. Viral Cytotoxicity Is Direct or Immunologically Mediated the means by which viruses cause cell injury and death are as diverse as viruses themselves. Unlike bacteria, a virus requires a cellular host to (1) house it; (2) provide enzymes, substrates, and other resources for viral replication; and (3) serve as a source for dissemination when mature virions are ready to be spread to other cells. Viruses have evolved mechanisms by which they avoid biting the hand that feeds them (at least until they are ready for other hands). The ability of a virus to persist in an infected cell necessitates a parasitic, albeit temporary, relationship with the host cell. During this vulnerable phase, the virus plays a game of cat and mouse with the immune system as a device to evade elimination of the infected cell. This period is followed by a phase in which the virus disseminates, either by budding (which does not necessarily destroy the cell) or by lysis (which does). The mechanisms underlying virus-induced lysis of cells, however, are probably more complex. Ionizing Radiation Causes Oxidative Stress the term "ionizing radiation" connotes an ability to cause radiolysis of water, thereby directly forming hydroxyl radicals. For a nonproliferating cell, such as a hepatocyte or a neuron, the inability to divide is of little consequence. For a proliferating cell, however, the prevention of mitosis is a catastrophic loss of function. Once a proliferating cell can no longer divide, it dies by apoptosis, which rids the body of those cells that have lost their prime function. Whereas exposure to significant sources of radiation impairs the replicating capacity of cycling cells, massive doses of radiation may kill both proliferating and quiescent cells directly. Direct injury caused by virus infection, involving both depletion of cellular resources and activation of apoptotic signaling mechanisms. Mechanisms that lead to immunologically mediated destruction of virus-infected cells. Since viruses must avoid cell death before they have produced infectious progeny, they have evolved mechanisms to counteract this effect by upregulating anti-apoptotic proteins and inhibiting proapoptotic ones. Some viruses also encode proteins that induce apoptosis once daughter virions are mature (see. These arms of the immune system eliminate virus-infected cells by inducing apoptosis or by lysing the cell with complement (see. Chemicals Injure Cells Directly and Indirectly Innumerable chemicals can damage almost any cell in the body. The science of toxicology attempts to define the mechanisms that determine both target cell specificity and the mechanism of action of such chemicals. Toxic chemicals either: (1) interact directly with cellular constituents without requiring metabolic activation or (2) are themselves not toxic but are metabolized to yield an ultimate toxin that interacts with the target cell. Liver Necrosis Caused by the Metabolic Products of Chemicals excess it is highly toxic to the liver. Most acetaminophen is enzymatically converted in the liver to nontoxic glucuronide or sulfate metabolites. In addition, acetaminophen metabolism is accelerated by chronic alcohol consumption, an effect mediated by an ethanol-induced increase in the 3A4 isoform of P450. To summarize, metabolism of hepatotoxic chemicals by mixed-function oxidation leads to cell injury through covalent binding of reactive metabolites and peroxidation of membrane phospholipids. Chemicals That Are Not Metabolized Directly cytotoxic chemicals interact with cellular constituents: prior metabolic conversion is not needed. These studies have focused principally on those compounds that are converted to toxic metabolites. Each is metabolized by the mixed-function oxidase system of the endoplasmic reticulum and each causes liver cell necrosis. These hepatotoxins are metabolized differently, and it is possible to relate the subsequent evolution of lethal cell injury to the specific features of this metabolism. Abnormal G Protein Activity Leads to Functional Cell Injury Normal cell function requires the coordination of numerous activating and regulatory signaling cascades. Hereditary or acquired interference with correct signal transduction can result in significant cellular dysfunction, as illustrated by diseases associated with faulty G proteins. Inherited defects in G protein subunits can lead to constitutive activation of the protein. In one such hereditary syndrome, endocrine manifestations predominate, including multiple tumors in the pituitary and thyroid glands. Another G protein mutation appears to predominate in many cases of essential hypertension, in which exaggerated activation of G protein signaling results in increased vascular responsiveness to stimuli that cause vasoconstriction. Decreased responsiveness of G proteins to ligand­receptor interactions may also be caused by certain mutations in G protein subunits. In addition, G protein activity can be inhibited by certain bacterial products, the most important example being pertussis toxin, the cause of whooping cough. Although the mechanisms responsible for necrosis vary according to the nature of the insult and the organ involved, most instances of necrosis share certain mechanistic similarities. The model of necrotic cell death that has been studied most extensively in mechanistic terms is ischemic injury to cardiac myocytes. The sequence of events is admittedly unique to cardiac myocytes, but most features are pertinent to other cell types and injurious agents.

In the reference list medications 25 mg 50 mg cheap 100 mg solian overnight delivery, references should be arranged alphabetically by author and not numbered medicine xarelto solian 50 mg cheap. If reference is made to more than one publication by the same author(s) in the same year 300 medications for nclex solian 100mg with mastercard, suffixes (a schedule 8 medications list discount 100mg solian free shipping, b medications 7 rights purchase solian 50mg free shipping, c medicine emblem purchase solian 100 mg fast delivery, etc. Journal titles should be abbreviated as given in the National Center for Biotechnology Information U. References to personal communications, unpublished observations, preprints, and papers submitted for publication are given in parentheses at the appropriate location in the text, not in the list of references. Only papers that have been officially accepted for publication may be cited as "in press" in the reference list. 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