Defects in man in four steps of 4‐aminobutyric acid (GABA) metabolism may interefere with the function of this major inhibitory neurotransmitter. Glutamic acid decarboxylase, 4‐aminobutyric acid aminotransferase, succinic semialdehyde dehydrogenase, and homocarnosinase are closely identified with the brain, but two of these enzymes are expressed in cultured peripheral cells, which may permit novel approaches to the study of the metabolism and regulation of GABA.

Society has historically not taken a benign view of genetic disease. The laws permitting sterilization of the mentally re tarded~ and those proscribing consanguineous marriages are but two examples. Indeed as far back as the 5th-10th centuries, B.C.E., consanguineous unions were outlawed (Leviticus XVIII, 6). Case law has traditionally tended toward the conservative. It is reactive rather than directive, exerting its influence only after an individual or group has sustained injury and brought suit. In contrast, state legislatures have not been (...) inhibited in enacting statutes. Many of their products can be characterized as hasty, unnecessary, ill-conceived, and based on the heart rather than the head. Moreover the lack of expert consultation sought has also been remarkable. One state legislature, for example, has advocated immunization for sickle cell anemia! Many others have enacted laws for the screening of inborn errors of metabolism, e.g., phenylketon uria, but have poorly defined the lines of responsibility to secure compliance. A spate of specific disease-related bills has emerged in the u.S. Congress, each seeking recognition and appropriations. Sickle cell anemia, hemophilia, Cooley's anemia and Tay-Sachs disease have been among the front-runners for support. Finally, in 1975, Congress has begun to examine an omnibus bill concerning all forms of genetic disease. The bill, termed the National Genetic Diseases Act is, however, still far from being enacted. (shrink)

Inborn errors of vitamin B12 (cobalamin) metabolism are associated with homocystinuria and methylmalonic aciduria, either alone or in combination. A number of these disorders have provided the first evidence for the existence of important steps in the transport or metabolism of cobalamin in eukaryotic cells. Eight complementation classes have been defined on the basis of somatic cell hybridization studies. Although the majority of patients present in infancy or early childhood, some are not diagnosed until adolescence or later. (...) For some of these disorders, prenatal diagnosis and therapy with cobalamin during pregnancy has been attempted. Although only males have been described with cblE disease, all of these disorders are presumed to be autosomal recessive in inheritance. The clinical and laboratory aspects of the different complementation classes (cblA–cblG) are reviewed here. (shrink)

Genetic determinism labels the morally problematical claim that some socially significant traits, traits we care about, such as sexual orientation, gender roles, violence, alcoholism, mental illness, intelligence, are largely the results of the operation of genes and not much alterable by environment, learning or other human intervention. Genetic determinism does not require that genes literally fix these socially significant traits, but rather that they constrain them within narrow channels beyond human intervention. In this essay we analyze genetic determinism in light (...) of what is now known about the inborn error of metabolism phenylketonuria , which has for so long been the poster child ‘simple’ argument in favor of some form of genetic determinism. We demonstrate that this case proves the exact opposite of what it has been proposed to support and provides a strong refutation of genetic determinism in all its guises. (shrink)

Eugenics can be defined as the use of science applied to the qualitative and quantitative improvement of the human genome. The subject was initiated by Francis Galton with considerable support from Charles Darwin in the latter half of the 19th century. Its scope has increased enormously since the recent revolution in molecular genetics. Genetic files can be easily obtained for individuals either antenatally or at birth; somatic gene therapy has been introduced for some rare inborn errors of metabolism; (...) and gene manipulation of human germ-line cells will no doubt occur in the near future to generate organs for transplantation. The past history of eugenics has been appalling, with gross abuses in the USA between 1931 and 1945 when compulsory sterilization was practised; and in Germany between 1933 and 1945 when mass extermination and compulsory sterilization were performed. To prevent such abuses in the future statutory bodies, such as a genetics commission, should be established to provide guidance and rules of conduct for use of the new information and technologies as applied to the human genome. (shrink)

A variety of herbicides act by inhibiting the branched chain amino‐acid biosynthetic enzyme, acetolactate synthase (EC 4.1.3.18). The initial consequences of this event are 2‐ketoacid accumulation and amino‐acid starvation. Recent studies demonstrate that 2‐ketoacid imbalances play a significant role in the action of these herbicides; such imbalances may also be important in certain inborn errors of human metabolism.

Thirty years ago, a number of human inborn errors in carbohydrate metabolism were explored with specific enzymatic tests on blood samples (hemolysates). Hereditary galactosemia was the first example. When the inoperative step in galactose metabolism was specified, the basis for the diet therapy used on the galactosemic infants, namely galactose‐free diet, could be shown to be securely founded.As far as galactose metabolism is concerned, the cells of the infant are faced with two problems: (i) the conversion (...) of dietary lactose (galactosyl glucose) to glucose and its catabolites involved in energy metabolism, and (ii) the conversion of dietary glucose or lactose to galactosyl units of glycolipids and glycoprotein cell structures.Subsequent studies on microorganisms revealed several types of hereditary defect in galactose metabolism. One type which permits the bacteria to develop a normal carbohydrate pattern in their cell walls includes an enzyme defect, like that described in the cells of the galactosemic infant. Two other types, with the inability to synthesize UDPGlc or UDPGal from glucose, do not permit the bacteria to build the fabric of the normal bacterial cell wall. This is the subject for discussion. (shrink)

A pathogenic connection between autoreactive T cells, fungal infection, and carcinogenesis has been demonstrated in studies of human autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy as well as in a mouse model in which kinase-dead Ikkα knock-in mice develop impaired central tolerance, autoreactive T cell–mediated autoimmunity, chronic fungal infection, and esophageal squamous cell carcinoma, which recapitulates APECED. IκB kinase α is one subunit of the IKK complex required for NF-κB activation. IKK/NF-κB is essential for central tolerance establishment by regulating the development of medullary thymic (...) epithelial cells that facilitate the deletion of autoreactive T cells in the thymus. In this review, we extensively discuss the pathogenic roles of inborn errors in the IKK/NF-κB loci in the phenotypically related diseases APECED, immune deficiency syndrome, and severe combined immunodeficiency; differentiate how IKK/NF-κB components, through mTEC, T cells/leukocytes, or epithelial cells, contribute to the pathogenesis of infectious diseases, autoimmunity, and cancer; and highlight the medical significance of IKK/NF-κB in these diseases. IKK/NF-κB regulates the expression of many genes that encode proteins involved in many crucial biological functions, such as immunity, tissue homeostasis, and fungal/bacterial/viral infections. Also, IKKα plays anti-tumor activities in many organs independently of NF-κB pathways. Thus, an inborn error in one of these gene loci can cause severe human diseases through these complicated mechanisms. (shrink)

continent. 2.3 (2012): 218–223 Vijay Prashad. Arab Spring, Libyan Winter . Oakland: AK Press. 2012. 271pp, pbk. $14.95 ISBN-13: 978-1849351126. Nearly a decade ago, I sat in a class entitled, quite simply, “Corporations,” taught by Vijay Prashad at Trinity College. Over the course of the semester, I was amazed at the extent of Prashad’s knowledge, and the complexity and erudition of his style. He has since authored a number of classic books that have gained recognition throughout the world. The Darker (...) Nations , a peoples’ history of the Third World, sent defibrillating shockwaves through an academic world that had almost forgotten the epic scope and historic dignity of the non-aligned movement and post-colonial struggles. In his recent, award-winning work, Arab Spring, Libyan Winter , Prashad delves into his capacious knowledge of the Third World to excavate the discourses and narratives surrounding the upheavals of 2011. “Revolutions have no specific timetable,” states Prashad in the opening line of this exciting and provocative look at contemporary events. Instantly, an atmosphere of suspense emerges. The reader is alerted to the problem of history. Does the making of history then involve a suspension of historical time, or is it a continuous narrative structure into which events must eventually be integrated? Arab Spring, Libyan Winter shows that the answer to the question, “How is history made?” lies just as easily in the asking. The first half of the book works through the events that transpired to bring about the explosive popular uprisings of Arab Spring: Tunisia and Egypt, Yemen and Bahrain. But the events are not put together in a cohesive, chronological fashion. Using an uncommonly gripping style more akin to the folk-story motif of the djeli than to traditionally Orientalist academia, Prashad suspends a given situation, points out its components, and traces back the characters and genealogies that define each link before resuming a narrative. Every moment is an end to itself, and an origin of something different. Thus, the making of history becomes the suspension of its own progress, it’s catastrophic 'stability,' in a process of differentiation through inclusion. Empirically, one might suggest that history is a condition of time, and by extension, of the subject, but history is also an eminent producer of the Subject and her concept of time through memory and narrative. Hence, history is often overdetermined by a dominant narrative of the sovereign. The apparently chaotic composition of Prashad’s historicity is, then, an interstitial morphology of resistance. It illustrates that the time to act for the revolutionary lies in the gaps within the dominant historical realities. It points out the sorties of signifiers constituting nothing in the obliterated ruins of history. Through such illuminations, Arab Spring, Libyan Winter breaks through “the surface of history” to elaborate revolution’s snapping synapses, exploding interruptions and breaches, connecting flows. Messianic Politics It is tempting to think, 'History is either singular, or it is diffuse. It is either one coherent factual narrative, or it is comprised of the aletheia of the multitude.' Yet the reader finds Prashad examining the structure of history on multiple levels. For Prashad, world history is shaped by geographically defined political movements, such as communism or national liberation, with historical agents like the working class for the former and the nationalist militant for the latter. Religion, however, is another matter: “Religion has an unshakable eschatology which a post-utopian secular politics lacks.” Within the telos of religion, there appears on the horizon the image of Benjamin’s thoughts on messianic time—time as “a small fissure in the continuous catastrophe,” a break with history, may contain an ultimate redemption of the human beyond the political power struggle. Succoring the split between geo-political and utopian-religious (messianic) time in the context of Arab Spring, Prashad indicates that the base of “the deep desire and commitment to some form of democracy” is forged by the affinity between eschatological Islamist politics with the People. To think about the Subject of messianic time in the context of the lack of a “coherent timetable” for emancipatory politics, it is perhaps best to return to the modern tradition of Martin Luther King, Jr., whose prefigurative blending of liberation theology and emancipatory politics became most important during his works of 1963, the climactic year of “The Letter from a Birmingham Jail,” the March on Washington, and the bombing of the 16th Street Baptist Church. In “The Letter,” King states the point bluntly: Frankly, I have yet to engage in a direct-action campaign that was “well timed” in view of those who have not suffered unduly from the disease of segregation. For years now I have heard the word “wait!” It rings in the ear of every Negro with piercing familiarity. This “Wait” has almost always meant ‘Never.” We must come to see, with one of our distinguished jurists, that “justice too long delayed is justice denied.” The timing of rebellious action must not be a part of history. It must change history. The kairos appears spontaneous and untimely in its convulsive, shocking presence, yet it is, deeper still, a path, a longue durée , forged through diligent and rigorous praxis. King put a finer point on the path of historic liberation in his declaration in his 1963 speech at Western Michigan University: “[T]ime is neutral.... Somewhere along the way we must see that time will never solve the problem alone but that we must help time. Somewhere we must see that human progress never rolls in on the wheels on inevitability. It comes through the tireless efforts and the persistent work of dedicated individuals who are willing to be co-workers with God. Without this hard work, time itself becomes an ally of the insurgent and primitive forces of irrational emotionalism and social stagnation. We must always help time and realize that the time is always right to do right.” Time, then, exists in “the neutral,” while action must turn to the kairos , not only of taking time, but taking the right time. By turning our relation to time into kairos , we move time from its context within history to a duration between histories—the longue dure?e of Messianic time. The implementation of neutrality in this context suggests a broad space of time to extend through the valley of positive and negative. In Roland Barthes’s lectures from 1978, the neutral takes place in this minimal distance of non-conflict that exists outside of two extremes. It is, in the words of Maurice Blanchot, “the non-general, the non-generic, as well as the non-specific.” For Blanchot, the neutrality of time permeates life as death, impassive and beyond control; such is the neutrality of messianic time, which permeates the charge of history, changing the "I" into the "one." The neutrality of time therefore implicates history in a case against extremism, showing that the work of the radical is not to tend to any particular side, but to have the time to navigate through the terrible terrain of history by altering its course, its patterns and rhythms of movement, connection, sociality. Hence, one does not simply “make history,” one alters the course of history in accordance to “the right time.” The historical path toward emerging power is transmitted as a gesture to the outside of history, against history; a gesture as simple as reaching out. Thus a counterhistory, to use Foucault’s term, is brought forward as the guide of time past a point of no return, a Rubicon, the point where the normal path of history falls to the past. The subject, who must be the only true agent of history, facilitates time through helpfulness, and both the Subject and her history become decentered in relation to one another. Yet history negates the neutrality of time. As Barthes discloses, although the neutral is the “thought and practice of the nonconflictual, it is nevertheless bound to assertion, to conflict, in order to make itself heard.” Engaged with history, time is charged with a destiny, and becomes an opposition. As Prashad insists, “For Arab lands, the events of early 2011 were not the inauguration of a new history, but the continuation of an unfinished struggle that is a hundred years old.” The emergence of the Subject during Arab Spring did not conceive of a new history, but changed the path of history toward a different destiny. “Historical grievances combined with inflationary pressures now met with the subjective sense that victory might be at hand—this was not simply a protest to scream into the wind, but a protest to actually remove autocrats from their positions of authority. The facts of resistance had given way to the expectation of revolutionary change.” The negativity of this charge toward “revolutionary destiny” rendered control, as a positive force, seriously lacking. The lack of control lies in the problem that the Subject is not totally detemporalized or timeless, but untimely in her presence. The Subject is untimely, because her work is visionary, and it is only through such visionary work that the Rubicon can be crossed. Still, the crossing of this border is haunted by anxiety over an impending disaster that lays in wait. It is only through the form of what Benjamin calls divine violence, captivated not with the justice of the means, but the ends—the transformation of history—that a revelation of history’s traumatic foundations can be liberated, and patterns and rhythms of time developed throughout obscured traditions awakened. In this situation, the Subject appears to be outside of right, but setting the state to rights. Because her position is correct, in-so-far as the rebelling subject rebels due to a lack of recognition, her representation appears outside of the norm, which is mistaken as right. Therefore, such visionary work must be carried out through obscured traditions, underground, away from the surveillance of empire. Explaining his method from the start along the lines of Marx’s metaphor of the mole, Prashad insists, “It is the burrowing that is essential, not simply the emergence onto the surface of history.” Arab Spring, Libyan Winter is a book on uncharted networks of time, spread out over the 252 pages like an elaborate spider’s web of passages intertwining with and overwhelming the machinery of the state. Although untimely, Arab Spring was not a flash in the pan, or a Facebook or Twitter revolution. Prashad notes that the government’s suspension of these tools led to further radicalism by furthering communications through face-to-face encounters. In existential terms, Arab Spring might be thought of as a revolution of Being over techne , an uprising of the unchartable, infinite potential of the Other. The name of this Other is found in Chance. The faith of the revolution lies in the proper decentering of the subject, its giving to the Other of time, for only with respect to time does history actually appear on the horizon of the subject, rather than as an imposition. This time of historical agency appears as a moment when anything can happen—a revolutionary truth event where everything comes into question while being realized in its Otherness as a community of the people begins anew in the streets amidst discourse, friendship, reconfigurations of hegemony, and a becoming of a constituent power. Throwing a wrench into the gears of the “cobwebbed tradition” of Orientalism, the decentering of history in Arab Spring, Libyan Winter is a defining quality of its impassioned revolutionary cry. But perhaps the most paradigmatic points of the book emerge from the unexpected voices. To make the connection between the particular manifestations of revolutionary demands to the general historic terms of revolution, Prashad quotes an anonymous young Egyptian in Tahrir Square, who reminds us, “[T]he French Revolution took a very long time so the people could eventually get their rights.” Far from timelessness, the historicization of Arab Spring must exist precisely within the most uncanny appearance of time, as something that does not appear to come from the natural state of time as we know it, but in arriving has completely transformed the way that we understand time. Strange Monsters Revolution is never as simple as a revolt from below against a rusting structure of elites trying to remain in power. As with the French Revolution, Arab Spring consisted of complex familial ties, outside interests, and religious factions fighting alongside, often in awkward juxtaposition to, liberals, working class parties, farmers, and students. It is perhaps because of this historically difficult and incongruous composition that the Arabic word for revolution is thawra , referring to the image of the bull, or thawr , which has religious significance as a pagan deity for the Ancient Semitic tribes and Cartheginians. If Daniel Guérin was correct in saying, “Anarchism and Marxism drink from the same spring,” then it is quite a different oasis that drove the thirsty beast of revolution through what Prashad calls, “the Libyan labyrinth.” Recalling Bataille’s Acéphale, the intestinal labyrinth gains significance as the mode of metabolism and rumination in which, “(the Acephale) has lost himself, loses me with him, and in which I discover myself as him, in other words, as a monster.” Unraveling the discourse of the revolution, the flows of power and hegemony—from Qaddafi’s nationalist coup in 1969 to the wars with Chad from 1978 to 1987, the neoliberal reforms of the 1990s to, finally, the War on Terror—we find that the metabolic process of Libyan Winter ends in the production of oil. In a process of what Prashad calls “involution,” Qaddafi’s bellicose policies, along with his attempts to nationalize Islam together with oil, mutated the source of his power, turning his house against itself. Already a divided nation, with its two major cities on opposite geographic sides of the country, Libya became split between two opposed political powers—liberal reformists and staunch nationalists—as Qaddafi’s political disengagement manifested through what can only be described in psychoanalytic terms as a recursive passage a l’act (mysteriously calling Wikipedia “Kleenex,” declaring that opponents drank hallucinogens with their instant coffee, and so on). Prashad declares, “The mercurial style that Qaddafi adopted was not about his personality alone, but also a leader’s natural response to a system that relied upon power brokers whose own loyalty… did not have any ideological commitment to the system.” As in the case of other nations during Arab Spring, the true expression of revolt was an outward exposition of what had inwardly been happening in microcosmic societies throughout the realm—from indigenous tribes to political parties, for a century, the people, partly motivated by (and in resistance to) economic impositions of development, had been changing the traditional social compositions and participating in what Ruth Wilson Gilmore calls, “the relative autonomy of the movement from the leaders.” It was this empowerment of political reconfigurations taking place under the context of new democratic assemblages that shocked the elites and evoked such a powerful response. Unlike Qaddafi’s awkward policy choices and rants, real acts of power from the West were clear and decisive. Prashad sets the stages of war and diplomacy, far removed from the deserts, mountains, and cities that forged the backdrop of popular politics. Taking place under the now-classic architecture of the “four pillars” of US interests—oil, the War on Terror, Israel, and the circumvention of Iranian hegemony—we find elites rubbing elbows in “Heliopolist cocktail parties and hushed conferences in Kasr al-Ittihadiya” as well as the Concorde-Lafayette hotel in Paris, which provides the setting for a meeting of anti-Qaddafi figures consolidating their power. These scenes are buttressed with the careful portraiture of key historical actors. As Prashad brings the stage of history to life, we find the diplomats and liberals like Frank Wisner, whose career has brought him from Enron in the late 1990s to the Obama Administration, under the aegis of which he was meeting with Mubarak about military support during Arab Spring. We spy the provocateurs, for instance, gauche cavalier , Bernard Henri-Levy, who telephones Sarkozy from Benghazi about the need for more NATO air strikes. We follow the rebel military establishment as it suffers mysterious deaths and even more mysterious assents (like that of apparent CIA cohort, Khalifa Hifter). In each of these intriguing characters, we find different representations of the security state biopolitique: an oil-injected reification that drives Arab Spring from the resentment of rising food prices to the brink of implosion in Libyan Winter. Reminiscent of the scenes of Cold War soirées represented in old Bond films, the aristocratic fight for oil against democracy that was Libyan Winter presents a harsh truth that the new global crisis is simply the continuation of the old history: the global exploitation of capitalism waged against the imagination of the people. As Benjamin laments, “The labyrinth is the right path for the person who always arrives early enough at his destination. This destination is the marketplace.” Yet, “(t)he labyrinth is the habitat of… a humanity (a class) which does not want to know where its destiny is taking it.” Thus, the labyrinth leads, like the desert, only further into itself. As Blanchot explains, “The desert is even less certain than the world; it is never anything but the approach to the desert.” Only the visionary can take time out of the involution toward oblivion. It is here, in this approach to and escape from history, that we find ourselves within Benjamin’s Golgotha, Blanchot’s desert: A space of indeterminate uncertainty where we become familiar only with our own exile. Blanchot writes, “For the moderated and moderate man, the room, the desert, and the world are strictly determined places. For the man of the desert and the labyrinth, devoted to the error of a journey necessarily a little longer than his life, the same space will be truly infinite, even if he knows that it is not, all the more so since he knows it.” The desert, as allegory, provides an eschatology, a mortality in the destiny of Arab Spring. But any allegory of nature might lead to a labyrinthine eschatology (for example, in Bachelard, the forest presents "a limitless world"); the prescience of the untimely is always an uncanny acceptance of the infinite within the finite—the outside of what is understood. Transgenerational and occupied with the image of the future, the untimely makes otherness its home as it proceeds toward liberation. In the work of helping time navigate this dangerous passage of history, Prashad illustrates that the more violent break with history may have occurred in the peaceable struggles of Tahrir Square, and not in the military clashes of Qaddafi with his former Generals who defected to the CIA and NATO countries. It might be possible to suggest, then, that in the case of Tunisia and Egypt, the historical subject of the people was drawn together in a Dionysian dance of different rhythms in the marvelous realm of the ancients, while we fear that the case of Libya suggests an Apollonian future where time, itself, may lay dying under the machinic hand of history. The properly Nietzschean inversion would follow: time is dead, for history has killed it. Yet, if time is dead, struck down in Golgotha, exposed in the desert, mauled by the thawra , it is only in the present sense that it is rendered impossible outside of the context into which the untimely has thrown us. Thus, if history becomes an art of revolution, life as being-towards-death (death as the provocation of the neutrality of time) becomes what Benjamin calls “the allegory of resurrection” through the glorious ruins of history. Prashad ends his work with a rousing finale: “The time of the impossible has presented itself. In Egypt, where the appetite for the possibilities of the future are greatest, the people continue to assert themselves into Tahrir Square and other places, pushing to reinvigorate a Revolution that must not die… For them the slogan is simple: Down with the Present. Long live the Future. May it be so.&rdquo. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Alzheimer's Disease, Mild Cognitive Impairment, and the Biology of Intrinsic AgingThomas B. L. Kirkwood (bio)Keywordsaging, Alzheimer’s disease, genetic mutation, mild cognitive impairment, telomereThe article by Gaines and Whitehouse (2006) raises key questions about the uncertain relationship between (i) the intrinsic, "normal" aging process, and (ii) the clinicopathologic states represented by the labels of Alzheimer's disease (AD) and mild cognitive impairment (MCI). This short commentary offers a perspective on this (...) debate that is drawn from a consideration of underlying biological mechanisms.Because age is unquestionably the greatest single risk factor associated with AD and MCI, I begin by asking what we know about the intrinsic processes of aging. The central feature of current understanding of intrinsic aging is that it consists of the gradual, lifelong accumulation of a wide variety of molecular and cellular faults that begins very early in life and eventually leads to overt functional impairments resulting in age-related frailty, disability, and disease (Kirkwood 2005). This is an essentially bottom-up process. A strong consensus has emerged in recent years that there is no active program for aging and that there are no genetic factors that have evolved specifically to cause aging or age-related diseases. Unquestionably, there are genes that influence susceptibility to disease and even length of life, but these genes are genes for maintenance and repair functions, not for aging. It is the limitation in the past evolutionary pressure to invest in greater longevity than was required, within an environment where life was usually truncated by hazards such as starvation, injury, or infection, that means that our maintenance systems—good as they are—are insufficient to keep us going indefinitely. Added to this is the idea that there are probably also genes that program processes that are good for the young organism, but which may in later life have harmful effects. Processes like inflammation and apoptosis, which are seen to occur extensively in aged tissues, including brain, surely evolved to help cope with infection and cellular damage arising earlier in life. That they are called into play in aged tissues is a direct, but secondary, consequence of accumulated damage.With this general framework to understand the intrinsic biology of aging, let us now ask what we might expect a priori for the aging of an organ such [End Page 79] as the brain. Although we cannot pretend complete ignorance of how the brain actually does age, our enquiry can be based entirely on data from other organ systems, so we can develop our predictions about brain aging without prejudice.Aging begins very early during human development, faults accumulating from the first stages of embryonic development. Each time a cell divides, each of the daughter cells is likely to acquire a few new mutations. We know this from the estimates for the error rate in DNA replication and the size of the human genome. It is confirmed by direct evidence that at individual gene loci where mutations have been measured, mutation frequency increases with age (Morley 1998; Vijg 2000). In addition to replication errors, DNA is damaged on a daily basis to a very considerable degree by agents such as reactive oxygen species (free radicals), which are formed as byproducts of normal cellular metabolism. Although most of this damage is corrected by repair, the repair mechanisms themselves are not error free and additional mutations accumulate through this route. If a mutation is lethal to the cell, the cell dies and thus the mutation is eliminated. However, the majority of mutations are nonlethal, either because the mutation is recessive and the cell carries an intact gene copy on the other chromosome, because the gene is not currently required, or because the mutation produces only a delayed deleterious effect. Examples of genes that produce delayed deleterious effects include the genes responsible for familial AD. It is interesting to reflect that on statistical grounds alone, it is almost certain that each of us carries a randomly determined fraction of cells in our brains that bear amyloid precursor protein or presenilin mutations associated with AD. We also carry a heterogeneous array of random mutations that compromise essential cell maintenance functions. How many such... (shrink)

This paper exposes some examples of continuing murky thinking concerning holism. The exposure is a prelude to noting the importance of proximity in causal explanations of illnesses and wounds. The paper then draws attention to how the proximate should not hold exclusive sway regarding what constitutes best nursing treatment and care. The error of excessive preference for proximity is shown to be an error, using as an example the treatment of leg ulcers. One component of holism that can (...) be clearly expressed amounts therefore simply to the claim: resist the error of excessive proximity preference, resist the error of concentrating solely on nearness. It is left open whether there is any further sense to be gleaned from the holistic babble. (shrink)

Errors of judgment regarding pain sensations are not possible. Christopher Hill, in his paper ‘Introspective Awareness of Sensations’, argues that we do sometimes commit ‘errors of judgment’ and he draws on an example that involves the perception of pain to illustrate his point. I analyze Hill’s example and draw on other examples of pain sensations to show how errors of judgment are not possible. I argue that pain sensations appear to be causally shaped and in some cases generated solely by (...) beliefs, expectations and dispositional states. Changes in beliefs, expectations and dispositional states appear to change the sensation that is generated. If pain sensations are generated in the way that I suggest, then the fact that some of the influences that causally shape and generate a pain sensation are constantly subject to change means that there may be little ‘truth’ that can be objectively established regarding a belief about a pain sensation. If there is little ‘truth’ that can be objectively established about a pain sensation, it will be inaccurate to label an instance of pain avowal as an ‘error of judgment’, or to speak about judgments concerning pain in terms of truth or error more generally. (shrink)

How do English‐speaking children inflect nouns for plurality and verbs for the past tense? We assess theoretical answers to this question by considering errors of omission, which occur when children produce a stem in place of its inflected counterpart (e.g., saying “dress” to refer to 5 dresses). A total of 307 children (aged 3;11–9;9) participated in 3 inflection studies. In Study 1, we show that errors of omission occur until the age of 7 and are more likely with both sibilant (...) regular nouns (e.g., dress) and irregular nouns (e.g., man) than regular nouns (e.g., dog). Sibilant nouns are more likely to be inflected if they are high frequency. In Studies 2 and 3, we show that similar effects apply to the inflection of verbs and that there is an advantage for “regular‐like” irregulars whose inflected form, but not stem form, ends in d/t. The results imply that (a) stems and inflected forms compete for production and (b) children generalize both product‐oriented and source‐oriented schemas when learning about inflectional morphology. (shrink)

Since the modern age the attacks against faith and religious belief have been raised. One of the major arguments against the existence of God who is described in theistic religious holy books as Almighty and all loving God come in terms of suffering in human life and the presence of evil in the world created by God. The challenge according to the critics against the religious life and faith is how a believer can be considered rational in his faith while (...) there are many suffering in human life and evil in the world. The aim of this paper is to deal with this challenge and the solution is given on the basis of Islamic teachings. There are different responses for this challenge both in Islamic theology and Christian theology. This research is limited to Quranic teachings and the main claim as one possible response and defense for the presence of evil in human life is to point out that evil plays a main role in provoking inborn knowledge of God in human nature. Keywords - life, inborn, faith, Quran, evil. (shrink)

We provide a mathematical study of a model of energy metabolism and hemodynamics of glioma allowing a better understanding of metabolic modifications leading to anaplastic transformation from low grade glioma.This mathematical analysis allows ultimately to unveil the solution to a viability problem which seems quite pertinent for applications to medecine.

The anti-utopian technology critique of Ellul, Postman, and other important social analysts has been the primary mode of critical response to technological developments since the 1950s. However, this mode of technology critique has had a disappointingly small effect on the way we, as a society, receive technology. Rather than attribute this failure to the negativity of the anti-utopian perspective, this article suggests that there are other important and largely overlooked factors at work—in particular, the critics' inability to speak about technology (...) in a way that relates to us as social individuals coping with the contingencies and realities of the day-to-day use of technological devices. The purpose of this analysis is not to suggest that we abandon as irrelevant the work and ideas of technology critics such as Ellul and Postman but, on the contrary, to find a way to reframe their important ideas for wider acceptance. (shrink)

Ephecticism is the tendency towards suspension of belief. Epistemology often focuses on the error of believing when one ought to doubt. The converse error—doubting when one ought to believe—is relatively underexplored. This essay examines the errors of undue doubt. I draw on the relevant alternatives framework to diagnose and remedy undue doubts about rape accusations. Doubters tend to invoke standards for belief that are too demanding, for example, and underestimate how farfetched uneliminated error possibilities are. They mistake (...) seeing how incriminating evidence is compatible with innocence for a reason to withhold judgement. Rape accusations help illuminate the causes and normativity of doubt. I propose a novel kind of epistemic injustice, for example, wherein patterns of unwarranted attention to farfetched error possibilities can cause those error possibilities to become relevant. Widespread unreasonable doubt thus renders doubt reasonable and makes it harder to know rape accusations. Finally, I emphasise that doubt is typically a conservative force and I argue that the relevant alternatives framework helps defend against pernicious doubt-mongers. (shrink)

This essay argues that the new natural law theory (NNLT) propounds five errors that place it on a collision course with the traditional Thomistic understanding central to the moral magisterium of the Roman Catholic Church. These root errors are argued to be (1) the denial of the primacy of speculative over practical truth, (2) the negation of unified normative natural teleology expressed in the NNLT doctrine of the putative “incommensurability” of basic goods prior to choice, (3) failure to affirm the (...) transcendence of the common good, (4) negation of the essentially theonomic character of the natural law, and (5) the intentionalist construction of human action. The teaching of St. Thomas Aquinas is held to be a superior light for understanding Catholic moral life. National Catholic Bioethics Quarterly 13.1 (Spring 2013): 105–131. (shrink)

Whenever justification of classroom punishment has been attempted it has usually been on grounds that punishment acts either appropriately pedagogically, teaching students how to behave morally, or is a necessary evil that enables the practical running of the school so that it may carry out its educational business. By itself the first justification leaves punishment in schools as only an extension of wider social attitudes about the virtue of punishing perceived moral wrongdoing, rather than providing any distinct argument for punishment (...) specific to the special circumstances of the school. By highlighting an entanglement between the moral and the conventional, and between discipline and punishment, within the context of the school, I shall argue that the essentially contested nature of education and its purpose, and the related question of the school’s suitability as a venue for it, means that the school’s most promising defence of its use of punishment—that punishment of students might somehow be necessary for enabling the important educative business of the school—becomes undone. Schooling and education are not necessarily synonymous, and as schools provide only one vision of education—and this vision is contestable—then upholding the business of any one school in order for it to achieve its particular unsettled and disputed purpose is not a morally sufficient reason to coerce a student’s compliance through regimes of ‘harm intended as harm’. (shrink)

Some Catholic theologians are redefining the meaning of “direct” and “indirect” by including only the agent’s intention in defining the moral object, while simultaneously excluding the physical actions that the agent consciously and deliberately chooses. The net effect is that these theologians now approve of many kinds of abortions traditionally understood to be morally evil in situations of maternal–fetal vital conflict. Such an error has grave implications for Catholic bioethics and health care. When the intentionalist method is applied to (...) other disputed questions in bioethics, however, it becomes clear that its ideology is fundamentally erroneous. (shrink)

By using the concept of a uniformity, the Structuralists have given us a most useful means of representing approximations. In the second section of this paper, I have made use of this technique to show how we can deal with errors of measurement — imprecise explananda — in the context of theoretical explanation. As well as (I hope) providing further demonstration of the power of the Structuralist approach, this also serves to support the ontic conception of explanation by showing that (...) it can help us resolve substantial problems in the theory of explanation. (shrink)

Psionics is known in the West under the names of radiethesia and radionics - Radethesia was germin, which was used to diagnose the disease with the help of a diagnostic tool or pendulum. Radionics was the word used to describe the diagnosis of disease states. None of the terms were adequate because the manipulation of subtle energies has long been the goal of magic and, relatively recently, has concerned the desire to develop psychic means or methods of surveillance from a (...) distance. A lot of research in this direction was carried out in the former USSR, Czechoslovakia, and in America. (shrink)

The reprogramming of metabolism has been identified as one of the hallmarks of cancer. It is becoming more and more frequent to connect other diseases with metabolic reprogramming. This article aims to argue that metabolic reprogramming is not driven by disease but instead is the main hallmark of metabolism, based on its dynamic behavior that allows it to continuously adapt to changes in the internal and external conditions.

When the existing order cannot offer a solution, the solution to climate crisis must come from the radical left, and this is precisely why Karl Marx’s idea of ecosocialism is more important than ever. In this context, it is worth revisiting not only the legacy of István Mészáros’s theory of ‘social metabolism’ and that of his successors – who can be categorised as comprising the ‘metabolic rift school’, which includes John Bellamy Foster, Paul Burkett, and Brett Clark –, but (...) also Karl Marx’s own theory of metabolism. In order to highlight the contemporary importance of Marx’s theory of metabolism after its long suppression in the twentieth century, this paper aims at classifying the three different levels of Marx’s concept of ‘metabolic rift’, which also entails clarifying three different levels of ‘metabolic shift’ as the theoretical foundation for updating Marx’s theory of postcapitalism in the age of global ecological crisis. (shrink)

Descartes first invokes the errors of the senses in the Meditations to generate doubt; he suggests that because the senses sometimes deceive, we have reason not to trust them. This use of sensory error to fuel a sceptical argument fits a traditional interpretation of the Meditations as a work concerned with finding a form of certainty that is proof against any sceptical doubt. If we focus instead on Descartes's aim of using the Meditations to lay foundations for his new (...) science, his appeals to sensory error take on a different aspect. Descartes's new science is based on ideas innate in the intellect, ideas that are validated by the benevolence of our creator. Appeals to sensory error are useful to him in undermining our naïve faith in the senses and guiding us to an appreciation of innate ideas. However, the errors of the senses pose problems in the context of Descartes's appeals to God's goodness to validate innate ideas and natural propensities to belief. A natural tendency to sensory error is hard to reconcile with the benevolence of our creator. This paper explores Descartes's responses to the problems of theodicy posed by various forms of sensory error. It argues that natural judgements involved in our visual perception of distance, size and shape pose a problem of error that resists his usual solutions. (shrink)

Intermediary metabolism molecules are orchestrated into logical pathways stemming from history (L-amino acids, D-sugars) and dynamic constraints (hydrolysis of pyrophosphate or amide groups is the driving force of anabolism). Beside essential metabolites, numerous variants derive from programmed or accidental changes. Broken down, variants enter standard pathways, producing further variants. Macromolecule modification alters enzyme reactions specificity. Metabolism conform thermodynamic laws, precluding strict accuracy. Hence, for each regular pathway, a wealth of variants inputs and produces metabolites that are similar to (...) but not the exact replicas of core metabolites. As corollary, a shadow, paralogous metabolism, is associated to standard metabolism. We focus on a logic of paralogous metabolism based on diversion of the core metabolic mimics into pathways where they are modified to minimize their input in the core pathways where they create havoc. We propose that a significant proportion of paralogues of well-characterized enzymes have evolved as the natural way to cope with paralogous metabolites. A second type of denouement uses a process where protecting/deprotecting unwanted metabolites - conceptually similar to the procedure used in the laboratory of an organic chemist - is used to enter a completely new catabolic pathway. (shrink)

All candid philosophers, in setting out on their great task of coordinating and criticizing the whole range of human thought, must often feel embarrassed by the limitations of their own knowledge. Their difficulties in dealing with scientific thought have increased very greatly during the last thirty years. For, while science has been rapidly growing more complex and abstruse, philosophers have been tending to require a more intimate knowledge of it. They are no longer interested only in scientific methods ; they (...) are beginning to find significance in particular propositions and principles. Some of these cannot be comprehended in their entirety by anyone who has not submitted himself to a training so specialized and so severe as to be almost incompatible with the width of outlook that makes the philosopher. Accordingly, philosophers have abandoned all attempts to acquire their knowledge of certain branches of science from the original memoirs and expository treatises addressed to scientists; they have recourse to interpreters. (shrink)

Certain familiar theoretic claims of both popular and academic postmodernism are examined for their implications as to the necessary and desirable limits of social life. Taken to the end, these claims promote errancy as a means of freeing conduct from the constraints of foundation. But this kind of freedom, one which treats all limitation as pernicious, generates social action that is mechanical, scattered, and without substance—it is a pyrrhic emancipation which trades content for self-sufficiency and thus constitutes an empty life (...) of unhappy social dispersion. And yet an opportunity does remain to address the way a limit can also be inspiring if we think through how interpretation, a limit which is itself limited, invites nevertheless what Derrida glossed as joyous affirmation. Interpretation, though imperfect, offers powers that are genuine and enjoyable because these powers supply life with content and thus with the vitalizing collective and individual possibility of conduct which is affirmative (and disaffirmative). Perhaps it could even be said that interpretation emancipates us from the emptiness of pure freedom. (shrink)