Showing papers by "Columbia University published in 1995"
TL;DR: In this article, a model of a firm's market value as it relates to contemporaneous and future earnings, book values, and dividends is developed and analyzed, and two owners' equity accounting constructs provide the underpinnings of the model: the clean surplus relation applies and dividends reduce current book value but do not affect current earnings.
Abstract: . The paper develops and analyzes a model of a firm's market value as it relates to contemporaneous and future earnings, book values, and dividends. Two owners' equity accounting constructs provide the underpinnings of the model: the clean surplus relation applies, and dividends reduce current book value but do not affect current earnings. The model satisfies many appealing properties, and it provides a useful benchmark when one conceptualizes how market value relates to accounting data and other information.
Resume. L'auteur elabore et analyse un modele dans lequel il conceptualise la relation entre la valeur marchande d'une entreprise et ses benefices, ses valeurs comptables et ses dividendes actuels et futurs. Deux postulats de la comptabilisation des capitaux propres servent de charpente au modele: a) la relation du resultat global s'applique et b) les dividendes reduisent la valeur comptable actuelle sans influer, cependant, sur les benefices actuels. Le modele presente de nombreuses proprietes interessantes et il peut, fort utilement, servir de repere dans la conceptualisation de la relation entre la valeur marchande et les donnees comptables et autres renseignements.
4,983 citations
TL;DR: Injection of wild-type mice twice daily with the mouse protein resulted in a sustained 12 percent weight loss, decreased food intake, and a reduction of body fat from 12.2 to 0.7 percent, suggesting that the OB protein serves an endocrine function to regulate body fat stores.
Abstract: The gene product of the ob locus is important in the regulation of body weight. The ob product was shown to be present as a 16-kilodalton protein in mouse and human plasma but was undetectable in plasma from C57BL/6J ob/ob mice. Plasma levels of this protein were increased in diabetic (db) mice, a mutant thought to be resistant to the effects of ob. Daily intraperitoneal injections of either mouse or human recombinant OB protein reduced the body weight of ob/ob mice by 30 percent after 2 weeks of treatment with no apparent toxicity but had no effect on db/db mice. The protein reduced food intake and increased energy expenditure in ob/ob mice. Injections of wild-type mice twice daily with the mouse protein resulted in a sustained 12 percent weight loss, decreased food intake, and a reduction of body fat from 12.2 to 0.7 percent. These data suggest that the OB protein serves an endocrine function to regulate body fat stores.
4,708 citations
Posted Content•
TL;DR: The authors showed that countries with a high ratio of natural resource exports to GDP tended to have low growth rates during the subsequent period 1971-89, even after controlling for variables found to be important for economic growth, such as initial per capita income, trade policy, government efficiency, investment rates, and other variables.
Abstract: One of the surprising features of modern economic growth is that economies with abundant natural resources have tended to grow less rapidly than natural-resource-scarce economies. In this paper we show that economies with a high ratio of natural resource exports to GDP in 1971 (the base year) tended to have low growth rates during the subsequent period 1971-89. This negative relationship holds true even after controlling for variables found to be important for economic growth, such as initial per capita income, trade policy, government efficiency, investment rates, and other variables. We explore the possible pathways for this negative relationship by studying the cross-country effects of resource endowments on trade policy, bureaucratic efficiency, and other determinants of growth. We also provide a simple theoretical model of endogenous growth that might help to explain the observed negative relationship.
3,511 citations
TL;DR: It is argued that social factors such as socioeconomic status and social support are likely 'fundamental causes" of disease that affect multiple disease outcomes through multiple mechanisms, and consequently maintain an association with disease even when intervening mechanisms change.
Abstract: Over the last several decades, epidemiological studies have been enormously
successful in identifying risk factors for major diseases However, most of this
research has focused attention on risk factors that are relatively proximal causes of
disease such as diet, cholesterol level, exercise and the like We question the
emphasis on such individually-based risk factors and argue that greater attention
must be paid to basic social conditions if health reform is to have its maximum
effect in the time ahead There are two reasons for this claim First we argue that
individually-based risk factors must be contextualized, by examining what puts
people at risk of risks, if we are to craft effective interventions and improve the
nation's health Second, we argue that social factors such as socioeconomic status
and social support are likely 'fundamental causes" of disease that, because they
embody access to important resources, affect multiple disease outcomes throughmultiple mechanisms, and consequently maintain an association with disease even when intervening mechanisms change Without careful attention to these
possibilities, we run the risk of imposing individually-based intervention strategies
that are ineffective and of missing opportunities to adopt broad-based societal
interventions that could produce substantial health benefits for our citizens
3,483 citations
TL;DR: The results supported minority stress hypotheses: each of the stressors had a significant independent association with a variety of mental health measures and odds ratios suggested that men who had high levels of minority stress were twice to three times as likely to suffer also from high level of distress.
Abstract: This study describes stress as derived from minority status and explores its effect on psychological distress in gay men. The concept of minority stress is based on the premise that gay people in a heterosexist society are subjected to chronic stress related to their stigmatization. Minority stressors were conceptualized as: internalized homophobia, which relates to gay men's direction of societal negative attitudes toward the self; stigma, which relates to expectations of rejection and discrimination; and actual experiences of discrimination and violence. The mental health effects of the three minority stressors were tested in a community sample of 741 New York City gay men. The results supported minority stress hypotheses: each of the stressors had a significant independent association with a variety of mental health measures. Odds ratios suggested that men who had high levels of minority stress were twice to three times as likely to suffer also from high levels of distress.
3,209 citations
TL;DR: A theory was proposed to reconcile paradoxical findings on the invariance of personality and the variability of behavior across situations to account for individual differences in predictable patterns of variability across situations.
Abstract: A theory was proposed to reconcile paradoxical findings on the invariance of personality and the variability of behavior across situations. For this purpose, individuals were assumed to differ in (a) the accessibility of cognitive-affective mediating units (such as encodings, expectancies and beliefs, affects, and goals) and (b) the organization of relationships through which these units interact with each other and with psychological features of situations. The theory accounts for individual differences in predictable patterns of variability across situations (e.g., if A. then she X, but ifE then she Y), as well as for overall average levels of behavior, as essential expressions or behavioral signatures of the same underlying personality system. Situations, personality dispositions, dynamics, and structure were reconceptualized from this perspective. The construct of personality rests on the assumption that individuals are characterized by distinctive qualities that are relatively invariant across situations and over time. In a century of personality research, however, abundant evidence has documented that individual differences in social behaviors tend to be surprisingly variable across different situations. Although this finding has been interpreted as evidence against the utility of the personality construct, we show that it need not be and, on the contrary, that this variability reflects some of the essence of personality coherence. When personality is conceptualized as a stable system that mediates how the individual selects, construes, and processes social information and generates social behaviors, it becomes possible to account simultaneously for both the invariant qualities of the underlying personality and the predictable variability across situations in some of its characteristic behavioral expressions. In this article, we begin with a review of recent empirical data demonstrating that individuals are characterized not only by stable individual differences in their overall levels of behavior, but also by distinctive and stable patterns of behavior variability across situations. These findings invite a new conception of personality in which such patterns of variability are seen not as
3,089 citations
TL;DR: A major revival in the use of classical electrostatics as an approach to the study of charged and polar molecules in aqueous solution has been made possible through the development of fast numerical and computational methods to solve the Poisson-Boltzmann equation for solute molecules that have complex shapes and charge distributions.
Abstract: A major revival in the use of classical electrostatics as an approach to the study of charged and polar molecules in aqueous solution has been made possible through the development of fast numerical and computational methods to solve the Poisson-Boltzmann equation for solute molecules that have complex shapes and charge distributions. Graphical visualization of the calculated electrostatic potentials generated by proteins and nucleic acids has revealed insights into the role of electrostatic interactions in a wide range of biological phenomena. Classical electrostatics has also proved to be successful quantitative tool yielding accurate descriptions of electrical potentials, diffusion limited processes, pH-dependent properties of proteins, ionic strength-dependent phenomena, and the solvation free energies of organic molecules.
2,740 citations
TL;DR: In this paper, the authors provide a model of firm and industry dynamics that allows for entry, exit, and firm-specific uncertainty generating variability in the fortunes of firms, focusing on the impact of uncertainty arising from investment in research and exploration.
Abstract: This paper provides a model of firm and industry dynamics that allows for entry, exit, and firm-specific uncertainty generating variability in the fortunes of firms. It focuses on the impact of uncertainty arising from investment in research and exploration. It analyzes the behavior of individual firms in an evolving market place and derives optimal policies, including exit. Then it adds an entry process and aggregates the optimal behavior of all firms, including potential entrants, into a rational expectations Markov-perfect industry equilibrium and proves ergodicity of the equilibrium process. Numerical examples illustrate the detailed characteristics of the stochastic process generating industry structures.
2,423 citations
TL;DR: In this paper, the relationship between market value and accounting data concerning operating and financial activities is modeled as a linear model, where market value is assumed to equal the net present value of expected future dividends, and is shown, under clean surplus accounting, to also equal book value plus the expected future abnormal earnings.
Abstract: . This paper models the relation between a firm's market value and accounting data concerning operating and financial activities. Book value equals market value for financial activities, but they can differ for operating activities. Market value is assumed to equal the net present value of expected future dividends, and is shown, under clean surplus accounting, to also equal book value plus the net present value of expected future abnormal earnings (which equals accounting earnings minus an interest charge on opening book value).
A linear model specifies the dynamics of an information set that includes book value and abnormal earnings for operating activities. Model parameters represent persistence of abnormal earnings, growth, and accounting conservatism. The model is sufficiently simple to permit derivation of closed form expressions relating market value to accounting data and other information.
Three kinds of analyses develop from the model. The first set deals with value as it relates to anticipated realizations of accounting data. The second set examines in precise terms how value depends on contemporaneous realizations of accounting data. The third set examines asymptotic relations comparing market value to earnings and book values, and how earnings relate to beginning of period book values.
The paper demonstrates that in all three sets of analyses the conclusions hinge on the extent to which the accounting is conservative as opposed to unbiased. Further, the absence/presence of growth in operating activities is relevant if, and only if, the accounting is conservative.
Resume. Les auteurs presentent sous forme de modele la relation entre la valeur marchande d'une entreprise et les donnees comptables relatives a ses activites d'exploitation et ses activites financieres. La valeur comptable est egale a la valeur marchande lorsqu'il s'agit d'activites financieres, mais elle peut etre differente dans le cas des activites d'exploitation. Les auteurs supposent que la valeur marchande est egale a la valeur actualisee nette des dividendes futurs prevus et demontrent que, lorsqu'on applique la methode du resultat global, la valeur marchande est aussi egale a la valeur comptable additionnee de la valeur actualisee nette des benefices extraordinaires futurs prevus (qui sont egaux aux benefices comptables diminues de frais d'interet implicites sur la valeur comptable nette).
Un modele lineaire precise la dynamique d'un ensemble de donnees, incluant la valeur comptable et les benefices extraordinaires, relatives aux activites d'exploitation. Les parametres du modele traduisent la persistance des benefices extraordinaires, la croissance et le principe de prudence. Le modele est suffisamment simple pour permettre de deriver des expressions fermees qui mettent en relation la valeur marchande et les donnees comptables et autres.
Du modele se degagent trois formes d'analyses. La premiere porte sur la valeur, dans sa relation avec la materialisation anticipee des donnees comptables. La deuxieme porte sur l'examen precis du lien entre la valeur et la materialisation actuelle des donnees comptables. Enfin, la troisieme porte sur l'examen des relations asymptotiques a travers lesquelles se comparent la valeur marchande, d'une part, et les benefices et la valeur comptable, d'autre part, ainsi que sur la facon dont les benefices se rattachent aux valeurs comptables du debut de l'exercice.
Les auteurs etablissent que dans les trois formes d'analyses, les conclusions s'orientent vers la mesure dans laquelle, dans le domaine comptable, l'accent est mis sur la prudence par opposition a l'impartialite. En outre, l'absence ou la presence de croissance dans les activites d'exploitation n'est pertinente que si et seulement si le principe de prudence est applique a la comptabilite.
2,331 citations
TL;DR: In this article, the neutralino is considered as a superpartner in many supersymmetric theories, and the cosmological abundance of neutralino and the event rates for both direct and indirect detection schemes are discussed.
Abstract: There is almost universal agreement among astronomers that most of the mass in the Universe and most of the mass in the Galactic halo is dark. Many lines of reasoning suggest that the dark matter consists of some new, as yet undiscovered, weakly-interacting massive particle (WIMP). There is now a vast experimental effort being surmounted to detect WIMPS in the halo. The most promising techniques involve direct detection in low-background laboratory detectors and indirect detection through observation of energetic neutrinos from annihilation of WIMPs that have accumulated in the Sun and/or the Earth. Of the many WIMP candidates, perhaps the best motivated and certainly the most theoretically developed is the neutralino, the lightest superpartner in many supersymmetric theories. We review the minimal supersymmetric extension of the Standard Model and discuss prospects for detection of neutralino dark matter. We review in detail how to calculate the cosmological abundance of the neutralino and the event rates for both direct- and indirect-detection schemes, and we discuss astrophysical and laboratory constraints on supersymmetric models. We isolate and clarify the uncertainties from particle physics, nuclear physics, and astrophysics that enter at each step in the calculation. We briefly review other related dark-matter candidates and detection techniques.
2,047 citations
TL;DR: A near real-time recognition system with 20 complex objects in the database has been developed and a compact representation of object appearance is proposed that is parametrized by pose and illumination.
Abstract: The problem of automatically learning object models for recognition and pose estimation is addressed. In contrast to the traditional approach, the recognition problem is formulated as one of matching appearance rather than shape. The appearance of an object in a two-dimensional image depends on its shape, reflectance properties, pose in the scene, and the illumination conditions. While shape and reflectance are intrinsic properties and constant for a rigid object, pose and illumination vary from scene to scene. A compact representation of object appearance is proposed that is parametrized by pose and illumination. For each object of interest, a large set of images is obtained by automatically varying pose and illumination. This image set is compressed to obtain a low-dimensional subspace, called the eigenspace, in which the object is represented as a manifold. Given an unknown input image, the recognition system projects the image to eigenspace. The object is recognized based on the manifold it lies on. The exact position of the projection on the manifold determines the object's pose in the image. A variety of experiments are conducted using objects with complex appearance characteristics. The performance of the recognition and pose estimation algorithms is studied using over a thousand input images of sample objects. Sensitivity of recognition to the number of eigenspace dimensions and the number of learning samples is analyzed. For the objects used, appearance representation in eigenspaces with less than 20 dimensions produces accurate recognition results with an average pose estimation error of about 1.0 degree. A near real-time recognition system with 20 complex objects in the database has been developed. The paper is concluded with a discussion on various issues related to the proposed learning and recognition methodology.
TL;DR: In this article, the authors present evidence for a new model of individual differences in judgments and reactions, which holds that people's implicit theories about human attributes structure the way they understand and react to human actions and outcomes.
Abstract: In this target article, we present evidence for a new model of individual differences in judgments and reactions. The model holds that people's implicit theories about human attributes structure the way they understand and react to human actions and outcomes. We review research showing that when people believe that attributes (such as intelligence or moral character) are fixed, trait-like entities (an entity theory), they tend to understand outcomes and actions in terms of these fixed traits ("I failed the test because I am dumb" or "He stole the bread because he is dishonest"). In contrast, when people believe that attributes are more dynamic, malleable, and developable (an incremental theory), they tend to focus less on broad traits and, instead, tend to understand outcomes and actions in terms of more specific behavioral or psychological mediators ("I failed the test because of my effort or strategy" or "He stole the bread because he was desperate"). The two frameworks also appear to foster different r...
Posted Content•
TL;DR: In this paper, the authors present a model where social interactions create enough covariance across individuals to explain the high cross-city variance of crime rates, and compare the degree of social interaction across crimes, across geographic 1 units and across time.
Abstract: The high degree of variance of crime rates across space (and across time) is one of the oldest puzzles in the social sciences (see Quetelet (1835)). Our empirical work strongly suggests that this variance is not the result of observed or unobserved geographic attributes. This paper presents a model where social interactions create enough covariance across individuals to explain the high cross- city variance of crime rates. This model provides a natural index of social interactions which can compare the degree of social interaction across crimes, across geographic 1units and across time. Our index gives similar results for different data samples and suggests that the amount of social interactions are highest in petty crimes (such as larceny and auto theft), moderate in more serious crimes (assault, burglary and robbery) and almost negligible in murder and rape. The index of social interactions is also applied to non-criminal choices and we find that there is substantial interaction in schooling choice.
TL;DR: It is proposed that interneuron network oscillations, in conjunction with intrinsic membrane resonances and long-loop (such as thalamocortical) interactions, contribute to 40-Hz rhythms in vivo.
Abstract: Partially synchronous 40-Hz oscillations of cortical neurons have been implicated in cognitive function. Specifically, coherence of these oscillations between different parts of the cortex may provide conjunctive properties to solve the 'binding problem': associating features detected by the cortex into unified perceived objects. Here we report an emergent 40-Hz oscillation in networks of inhibitory neurons connected by synapses using GABAA (gamma-aminobutyric acid) receptors in slices of rat hippocampus and neocortex. These network inhibitory postsynaptic potential oscillations occur in response to the activation of metabotropic glutamate receptors. The oscillations can entrain pyramidal cell discharges. The oscillation frequency is determined both by the net excitation of interneurons and by the kinetics of the inhibitory postsynaptic potentials between them. We propose that interneuron network oscillations, in conjunction with intrinsic membrane resonances and long-loop (such as thalamocortical) interactions, contribute to 40-Hz rhythms in vivo.
TL;DR: In this article, the authors examine the concept of technological opportunity and discuss three categories of sources of those opportunities: advances in scientific understanding and technique, technological advances originating in other industries and in other private and governmental institutions, and feedbacks from an industry's own technological advances.
TL;DR: A novel mutation in the CYP19 gene in a sister and brother exhibited the cardinal features of the aromatase deficiency syndrome as recently defined and was reported on.
Abstract: The aromatase enzyme complex catalyzes the conversion of androgens to estrogens in a wide variety of tissues, including the ovary, testis, placenta, brain, and adipose tissue. Only a single human gene encoding aromatase P450 (CYP19) has been isolated; tissue-specific regulation is controlled in part by alternative promoters in a tissue-specific manner. We report a novel mutation in the CYP19 gene in a sister and brother. The 28-yr-old XX proband, followed since infancy, exhibited the cardinal features of the aromatase deficiency syndrome as recently defined. She had nonadrenal female pseudohermaphrodism at birth and underwent repair of the external genitalia, including a clitorectomy. At the age of puberty, she developed progressive signs of virilization, pubertal failure with no signs of estrogen action, hypergonadotropic hypogonadism, polycystic ovaries on pelvic sonography, and tall stature. The basal concentrations of plasma testosterone, androstenedione, and 17-hydroxyprogesterone were elevated, wher...
TL;DR: A linear zipper of molecules that mirrors the linear structure of the intracellular filaments with which cadherins associate may provide a mechanism to marshal individual molecular adhesive interactions into strong bonds between cells.
Abstract: Crystal structures of the amino-terminal domain of N-cadherin provide a picture at the atomic level of a specific adhesive contact between cells. A repeated set of dimer interfaces is common to the structure in three lattices. These interactions combine to form a linear zipper of molecules that mirrors the linear structure of the intracellular filaments with which cadherins associate. This cell-adhesion zipper may provide a mechanism to marshal individual molecular adhesive interactions into strong bonds between cells.
TL;DR: The receptor for advanced glycation end products (RAGE), a newly-identified member of the immunoglobulin superfamily, mediates interactions of AGE-modified proteins with endothelium and other cell types.
TL;DR: The same herpesvirus-like DNA sequences are present in AIDS-associated Kaposi's sarcoma, classic Kaposi’s sarcomo, and the Kaposi' sarcoma that occurs in HIV-negative homosexual men, suggesting that all three are caused by the same infectious agent.
Abstract: Background Herpesvirus-like DNA sequences have recently been found in lesions from patients with Kaposi's sarcoma and the acquired immunodeficiency syndrome (AIDS). It is not known whether these sequences are also present in classic Kaposi's sarcoma or in the Kaposi's sarcoma that occurs in homosexual men who are seronegative for the human immunodeficiency virus (HIV). Methods We analyzed DNA in tissue samples from patients with AIDS-associated Kaposi's sarcoma, patients with classic Kaposi's sarcoma, and HIV-seronegative homosexual men with Kaposi's sarcoma. We also analyzed DNA in samples of uninvolved tissue from these patients and in control tissue from healthy subjects. All samples were tested blindly by polymerase chain reaction (PCR) with specific primers to amplify KS330233, a herpesvirus-like DNA sequence. Results The KS330233 PCR product was found in 20 of 21 tissue samples (95 percent) from the patients with Kaposi's sarcoma, including 10 of the 11 samples from the patients with AIDS-associated...
TL;DR: A novel role for amino acid neurotransmitters in regulating neocortical neurogenesis is found, and applied alone, GABAA and AMPA/kainate receptor antagonists increase DNA synthesis, indicating that endogenously released amino acids influence neocorticals progenitors in the cell cycle.
TL;DR: In this article, the authors examined how small firms differ in their competitive behaviors from their large rivals in an industry and explored the implications of differences for performance, using data on competitive mo...
Abstract: This study examined how small firms differ in their competitive behaviors from their large rivals in an industry and explored the implications of differences for performance. Data on competitive mo...
TL;DR: Findings reveal that CNS nAChRs enhance fast excitatory transmission, providing a likely mechanism for the complex behavioral effects of nicotine.
Abstract: The behavioral and cognitive effects of nicotine suggest that nicotinic acetylcholine receptors (nAChRs) participate in central nervous system (CNS) function. Although nAChR subunit messenger RNA (mRNA) and nicotine binding sites are common in the brain, there is little evidence for synapses mediated by nAChRs in the CNS. To test whether, CNS nAChRs might modify rather than mediate transmission, the regulation of excitatory synaptic transmission by these receptors was examined. Nanomolar concentrations of nicotine enhanced both glutamatergic and cholinergic synaptic transmission by activation of presynaptic nAChRs that increased presynaptic [Ca2]i. Pharmacological and subunit deletion experiments reveal that these presynaptic nAChRs include the alpha 7 subunit. These findings reveal that CNS nAChRs enhance fast excitatory transmission, providing a likely mechanism for the complex behavioral effects of nicotine.
TL;DR: The work s ummarized in this review has helped answer a long-standing question: How can wellknown behavioral, cognit ive, and addict ive eff ects of ni cotine be reconci led with the paucity of evidence for CNS s ynapses where t he t rans mission is mediat ed by nicot inic recept ors?
Abstract: The last decade has revealed an astounding degree of physiological and st ruct ural divers it y in neurot ransmitteract ivated receptors. In part icular, mo lecular st udies of the acet ylcholine-gated recept ors in vert ebrate muscle cells and Torpedo elect rocyt es gave birt h to a new era of research on a relat ed s ubfamil y of nicotinic r eceptors ( nA Ch Rs) expressed by centr al and periph eral neurons. Th is review focuses on the nA ChR s ubt ypes expressed by neurons , viewed mainly from a ph ys iological pers pect ive. It is intended t o complement s everal excellent recent reviews o n muscle-type A ChRs (42, 45, 56) and on the anatomi cal dist ri buti on, bi ochemistry, and molecular bi ology of neuronal nAChRs (35, 61, 66, 95). The work s ummarized in this review has helped answer a long-standing q uest ion: How can t he wellknown behavioral, cognit ive, and addict ive eff ects of ni cotine be reconci led with the paucity of evidence for CNS s ynapses where t he t rans mission is mediat ed by nicot inic recept ors? The ident ificat ion of a large family of neuronal nA ChR s ubu nit genes and an array of funct ionally dist inct nA ChRs has given a bas is for t he divers e effects of nicot ine. P erhaps
22 May 1995
TL;DR: This paper details the sorted neighborhood method that is used by some to solve merge/purge and presents experimental results that demonstrates this approach may work well in practice but at great expense, and shows a means of improving the accuracy of the results based upon a multi-pass approach.
Abstract: Many commercial organizations routinely gather large numbers of databases for various marketing and business analysis functions. The task is to correlate information from different databases by identifying distinct individuals that appear in a number of different databases typically in an inconsistent and often incorrect fashion. The problem we study here is the task of merging data from multiple sources in as efficient manner as possible, while maximizing the accuracy of the result. We call this the merge/purge problem. In this paper we detail the sorted neighborhood method that is used by some to solve merge/purge and present experimental results that demonstrates this approach may work well in practice but at great expense. An alternative method based upon clustering is also presented with a comparative evaluation to the sorted neighborhood method. We show a means of improving the accuracy of the results based upon a multi-pass approach that succeeds by computing the Transitive Closure over the results of independent runs considering alternative primary key attributes in each pass.
TL;DR: Sequence analysis indicates that a family of about 30 putative receptor genes comprise a novel family of seven transmembrane domain proteins unrelated to the receptors expressed in the MOE, likely to encode mammalian pheromone receptors.
TL;DR: In this article, the intramolcular dynamical properties of E. coli coliribonuclease H, including spin-lattic relaxation rate, spin-spin relaxation rate constants, and steady state nuclear Overhauser effects for the 15N nuclear spins were measured by using proton-detected heteronuclear NMR spectroscopy.
TL;DR: A degenerate peptide library is used to show that each of nine tyrosine kinases investigated has a unique optimal peptide substrate, and indicates that a point mutation in the RET receptor-type tyosine kinase, which causes multiple endocrine neoplasia type 2B, results in a shift in peptide substrates specificity.
Abstract: HOW do distinct protein-tyrosine kinases activate specific downstream events? Src-homology-2 (SH2) domains on tyrosine kinases or targets of tyrosine kinases recognize phosphotyrosine in a specific sequence context and thereby provide some specificity1–3. The role of the catalytic site of tyrosine kinases in determining target specificity has not been fully investigated. Here we use a degenerate peptide library to show that each of nine tyrosine kinases investigated has a unique optimal peptide substrate. We find that the cytosolic tyrosine kinases preferentially phosphorylate peptides recognized by their own SH2 domains or closely related SH2 domains (group I; ref. 3), whereas receptor tyrosine kinases preferentially phosphorylate peptides recognized by subsets of group III SH2 domains3. The importance of these findings for human disease is underscored by our observation that a point mutation in the RET receptor-type tyrosine kinase, which causes multiple endocrine neoplasia type 2B, results in a shift in peptide substrate specificity.
TL;DR: Data are consistent with the hypothesis that AGE-RAGE interaction induces expression of VCAM-1 which can prime diabetic vasculature for enhanced interaction with circulating monocytes.
Abstract: Vascular cell adhesion molecule-1 (VCAM-1), an inducible cell-cell recognition protein on the endothelial cell surface (EC), has been associated with early stages of atherosclerosis. In view of the accelerated vascular disease observed in patients with diabetes, and the enhanced expression of VCAM-1 in diabetic rabbits, we examined whether irreversible advanced glycation endproducts (AGEs), could mediate VCAM-1 expression by interacting with their endothelial cell receptor (receptor for AGE, RAGE). Exposure of cultured human ECs to AGEs induced expression of VCAM-1, increased adhesivity of the monolayer for Molt-4 cells, and was associated with increased levels of VCAM-1 transcripts. The inhibitory effect of anti-RAGE IgG, a truncated form of the receptor (soluble RAGE) or N-acetylcysteine on VCAM-1 expression indicated that AGE-RAGE-induced oxidant stress was central to VCAM-1 induction. Electrophoretic mobility shift assays on nuclear extracts from AGE-treated ECs showed induction of specific DNA binding activity for NF-kB in the VCAM-1 promoter, which was blocked by anti-RAGE IgG or N-acetylcysteine. Soluble VCAM-1 antigen was elevated in human diabetic plasma. These data are consistent with the hypothesis that AGE-RAGE interaction induces expression of VCAM-1 which can prime diabetic vasculature for enhanced interaction with circulating monocytes.
TL;DR: There was no initiation into alcohol and cigarettes and hardly any initiation into illicit drugs after age 29, the age at which most use ceased, and Cigarettes are the most persistent of any drug used.
Abstract: OBJECTIVES This study sought to describe patterns of initiation, persistence, and cessation in drug use in individuals from their late 20s to their mid-30s, within a broad perspective that spans 19 years from adolescence to adulthood METHODS A fourth wave of personal interviews was conducted at ages 34-35 with a cohort of men and women (n = 1160) representative of adolescents formerly enrolled in New York State public secondary high schools A school survey was administered at ages 15-16, and personal interviews with participants and school absentees were conducted at ages 24-25 and 28-29 Retrospective continuous histories of 12 drug classes were obtained at each follow-up RESULTS There was no initiation into alcohol and cigarettes and hardly any initiation into illicit drugs after age 29, the age at which most use ceased The largest proportion of new users was observed for prescribed psychoactives Periods of highest use since adolescence based on relative and absolute criteria were delineated Am