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 collection of essays addresses some of the central issues in modern social and political thought, such as: the revival of Marxism and its relevance to the social sciences; the analysis of social and political structures and social movements; and the future of advanced capitalist societies.

The comic is one of the principal esthetic categories; it unites the multifaceted experience of the social mind as it assimilates and cognizes the world, particularly the social world, on the basis of axioms of common sense, or even of public opinion about these axioms. Boldly violating the laws of logic and the verisimilitude of images, of normal connections and notions, and playing upon these violations, the comic nonetheless remains firmly on the side of common sense. The comic is inexhaustible (...) in its nuances — from light merriment and entertainment to malicious ridicule and satire, from gross farce to subtle forms of irony and humor. (shrink)

My chief object in these notes is to provide evidence for tracing the ancestry of certain themes, situations, and characters which appear in New Comedy; I hope, however, that they may also be useful for the study of Middle Comedy itself. I am therefore chiefly concerned with the period from 400 b.c. to 320 b.c., when Menander had begun to write; I have, however, given some dates after 320 which were necessary to complete my story, but I have left out (...) many plays by poets of New Comedy which can be dated in the decade 320–310 b.c. I have also omitted the originals of Plautus Amphitruo, Persa, and Menaechmi, although I am convinced that they all belong to Middle Comedy and hope to consider the problem more fully elsewhere; the tactics of the battle in the Amphitruo are possible for Epameinondas and Philip as well as for Alexander, but the clash of two kings seems to limit the reference to Alexander and Dareios as depicted in the famous mosaic, and the limits are 330–320 ; the original of the Persa must have been written before Alexander's conquests and the limits seem to be 345–338; Hueffher's late dating of the original of the Menaechmi has been successfully countered by Fraenkel and the whole feel of the play suggests Middle rather than New Comedy. The following list is arranged in decades, except where it has proved necessary to use a longer period. I have tabulated first the plays or victories dated by inscriptional or other firm evidence; among these I have included the plays dated by Geissler, without comment except where I disagree with him. (shrink)

Professor Beare has attacked the position established by Alfred Körte in 1893 and accepted in large measure by Sir Arthur Pickard-Cambridge in Dithyramb, etc., and Festivals. The following reply is brief because I have dealt with the works of art at some length in Rylands Bulletin, xxxvi , 563 f. and in a forthcoming number of Ephemeris Archaiologike. The statement of Aristotle . I have tried to show that various elements in the ‘phallic performances’ were taken over by comedy and (...) that we have some evidence that the leaders of padded dancers wore the phallos. (shrink)

The late Sir George Hill in the first volume of his monumental History of Cyprus remarks that the Cypriot syllabary is found in use until the third century B.C. This, it may be noted, is the traditional opinion which for some sixty years has stood the test of time. I read therefore with interest on p. 330 of the same volume, among the addenda, that ‘pottery with incised inscriptions, discovered in 1939 in an excavation four miles from Nicosia, shows that (...) the syllabary continued to be used as late as the first century B.C.’ Sir George Hill in effect is here accepting the claim of Mrs. E. H. Dohan and Professor R. G. Kent, which he has hitherto ignored, that the syllabary survived until 50 B.C. Now this is an important claim, partly because it would add from two to three centuries to the life-span of a script already in possession of a long and reputable lineage; more particularly because, if true, it will convict the ancient Cypriot, admittedly a conservative individual, of a degree of conservatism with which I find it hard to credit even him. That there should still have been men in the hinterland of the island under the governorship of Cicero so little affected by the impact of the whole Hellenistic age that they were prepared to write Greek in a manner so uncouth and preserve, incidentally, certain elements of their old Arcadian tongue, is to my thinking highly improbable. A fresh examination of the evidence on which Mrs. Dohan and Professor Kent based their claim is clearly called for. (shrink)

The Court of Appeals of Minnesota, in State v. Saunders ), held that the statutory offense of practicing medicine without a license was not unconstitutionally vague as applied to a claim involving a farmer who offered a home remedy to cure cancer. The court held that, although Minnesota Statute § 147.081 subd. 3 contains general language and undefined terms, the statute contains sufficient particularity to show ordinary persons what conduct is prohibited, and thereby passes the void-for-vagueness test. The court stated (...) that, according to the statute, while a person holding a license to practice medicine is permitted to engage in a broad range of conduct, those without that license are proscribed from engaging in that same range of conduct.The defendant, Mr. Saunders, a dairy farmer, claimed that he could cure ill people by injecting an ill person's blood into a cow and then feeding that person the cow's colostrum. (shrink)

In this paper we consider the effect of unitarity bounds sb⩾s≡(E1+E2) cms 2 for the recently proposed types of nonderivative 4-fermion contact interactions. To this purpose we decompose the helicity amplitudes at c.m.s. into partial waves. The bounds are defined to hold for all reaction channels due to the same type of contact interaction. We find sb=τ4π/κ. Here κ is the coupling constant. The factor τ depends on the type of coupling and on the different cases to identify the fermions. (...) It ranges from 1/3 to 4. (shrink)