405 research outputs found

    An economic analysis of alternative beef cattle systems for a large farm in central Missouri

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    Published in cooperation with the Economic Research Service, United States Department of Agriculture.Digitized 2007 AES.Includes bibliographical references (page 39)

    Seeing Crime and Punishment Through a Sociological Lens: Contributions, Practices, and the Future

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    There is a rich intellectual history to the sociological study of crime and punishment that encompasses multiple and interrelated traditions. Some of these traditions trace their roots to the European social theorists of the nineteenth century, particularly Emile Durkheim, Max Weber, and Karl Marx. Although only Durkheim and Weber systematically studied law (and only Durkheim actually studied punishment), all three social theorists facilitated the development of sociological research and theory on crime and punishment. Durkheim\u27s Suicide: A Study in Sociology, for example, investigated the relationship between social integration and suicide rates, which, in turn, provided a model of inquiry for multiple generations of sociologists investigating the social causes of crime, delinquency, and social deviance. Similarly, Durkheim\u27s The Division of Labor in Society inspired sociologists to examine the relationship between social structure and the organization of law and punishment. Weber\u27s ideas concerning the rationalization of society and the legitimate bases of legal authority compelled sociologists to think comparatively and brought a historical dimension to sociological inquiry on law and punishment. Marxist sensibilities begat a small, but vibrant, industry of radical criminologists and sociologists of law and punishment who located both the causes and control of crime in the exploitation, injustice, and class conflict inherent in capitalist society

    Neurodevelopment and ages of onset in depressive disorders

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    How and why do clinical depressive disorders emerge in adolescence? In this Personal View, we present a neurodevelopmental theory to address causes for adolescent onsets of clinical depressive disorders. We argue that theories should account for three perplexing aspects of depressive disorders in adolescence: the episodic nature of depression; differences between sexes in rates of depression across development; and age-differentiated onsets. We consider how theories such as psychosocial acceleration, heterochronic brain development, dual-process models, glucocorticoid vulnerability hypothesis linked to early life stress, and epigenetic and genetic susceptibility might explain some aspects of adolescent depressive disorders. We argue that some synthesis between existing theories might be needed to establish a sufficient neurodevelopmental theoretical framework to explain onsets of depressive disorders in adolescence

    Lin28A and Lin28B Inhibit let-7 MicroRNA Biogenesis by Distinct Mechanisms

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    SummaryLin28A and Lin28B selectively block the expression of let-7 microRNAs and function as oncogenes in a variety of human cancers. Lin28A recruits a TUTase (Zcchc11/TUT4) to let-7 precursors to block processing by Dicer in the cell cytoplasm. Here we find that unlike Lin28A, Lin28B represses let-7 processing through a Zcchc11-independent mechanism. Lin28B functions in the nucleus by sequestering primary let-7 transcripts and inhibiting their processing by the Microprocessor. The inhibitory effects of Zcchc11 depletion on the tumorigenic capacity and metastatic potential of human cancer cells and xenografts are restricted to Lin28A-expressing tumors. Furthermore, the majority of human colon and breast tumors analyzed exclusively express either Lin28A or Lin28B. Lin28A is expressed in HER2-overexpressing breast tumors, whereas Lin28B expression characterizes triple-negative breast tumors. Overall our results illuminate the distinct mechanisms by which Lin28A and Lin28B function and have implications for the development of new strategies for cancer therapy

    Adolescent Major Depressive Disorder: Neuroimaging Evidence of Sex Difference during an Affective Go/No-Go Task

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    Compared to female major depressive disorder (MDD), male MDD often receives less attention. However, research is warranted since there are significant sex differences in the clinical presentation of MDD and a higher rate of suicide in depressed men. To the best of our knowledge, this is the first functional magnetic resonance imaging (fMRI) study with a large sample addressing putative sex differences in MDD during adolescence, a period when one of the most robust findings in psychiatric epidemiology emerges; that females are twice as likely to suffer from MDD than males. Twenty-four depressed and 10 healthy male adolescents, together with 82 depressed and 24 healthy female adolescents, aged 11–18 years, undertook an affective go/no-go task during fMRI acquisition. In response to sad relative to neutral distractors, significant sex differences (in the supramarginal gyrus) and group-by-sex interactions (in the supramarginal gyrus and the posterior cingulate cortex) were found. Furthermore, in contrast to the healthy male adolescents, depressed male adolescents showed decreased activation in the cerebellum with a significant group-by-age interaction in connectivity. Future research may consider altered developmental trajectories and the possible implications of sex-specific treatment and prevention strategies for MDD

    Complex interactions of HIV-1 nucleocapsid protein with oligonucleotides

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    The HIV-1 nucleocapsid (NC) protein is a small, basic protein containing two retroviral zinc fingers. It is a highly active nucleic acid chaperone; because of this activity, it plays a crucial role in virus replication as a cofactor during reverse transcription, and is probably important in other steps of the replication cycle as well. We previously reported that NC binds with high-affinity to the repeating sequence d(TG)(n). We have now analyzed the interaction between NC and d(TG)(4) in considerable detail, using surface plasmon resonance (SPR), tryptophan fluorescence quenching (TFQ), fluorescence anisotropy (FA), isothermal titration calorimetry (ITC) and electrospray ionization Fourier transform mass spectrometry (ESI-FTMS). Our results show that the interactions between these two molecules are surprisngly complex: while the K(d) for binding of a single d(TG)(4) molecule to NC is only ∼5 nM in 150 mM NaCl, a single NC molecule is capable of interacting with more than one d(TG)(4) molecule, and conversely, more than one NC molecule can bind to a single d(TG)(4) molecule. The strengths of these additional binding reactions are quantitated. The implications of this multivalency for the functions of NC in virus replication are discussed

    Eight Weeks of Treatment With Glecaprevir/Pibrentasvir Is Safe and Efficacious in an Integrated Analysis of Treatment-Naïve Patients With Hepatitis C Virus Infection

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    BACKGROUND & AIMS: The direct-acting antiviral combination glecaprevir/pibrentasvir has been approved by the Food and Drug Administration for 8 weeks of treatment in treatment-naïve patients with hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis. We performed an integrated analysis of data from trials to evaluate the overall efficacy and safety of 8 weeks of glecaprevir/pibrentasvir in treatment-naïve patients without cirrhosis or with compensated cirrhosis. METHODS: We pooled data from 8 phase 2 or phase 3 trials of treatment-naïve patients with HCV genotype 1 to 6 infections, without cirrhosis or with compensated cirrhosis, who received 8 weeks of glecaprevir/pibrentasvir. RESULTS: Of 1248 patients, 343 (27%) had cirrhosis. Most patients were white (80%) and had HCV genotype 1 infection (47%) or genotype 3 infection (22%); the median age was 54 years. Overall rates of sustained virologic response at post-treatment week 12 were 97.6% (1218 of 1248) in the intention to treat (ITT) and 99.3% (1218 of 1226) in the modified ITT populations. When we excluded patients with genotype 3 infections with compensated cirrhosis (consistent with the European label), rates of sustained virologic response at post-treatment week 12 were 97.6% in the ITT and 99.4% in the modified ITT populations. Eight virologic failures (7 in patients without cirrhosis and 1 in a patient with cirrhosis) occurred in the ITT population. Virologic failure was not associated with markers of advanced liver disease or populations of interest (current alcohol use, opioid substitution therapy, history of injection-drug use, and severe renal impairment). Treatment-emergent adverse events (AEs) occurred in 58% of patients. The most frequent AEs (>10%) were headache (12%) and fatigue (12%). Serious AEs and AEs that led to glecaprevir/pibrentasvir discontinuation were reported in 2% and less than 1% of patients, respectively. CONCLUSIONS: In a pooled analysis of data from 8 trials, we found that 8 weeks of treatment with glecaprevir/pibrentasvir is efficacious and well tolerated in treatment-naïve patients with HCV genotype 1 to 6 infections, with or without cirrhosis.status: publishe
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