I Am Not Bound To Win Abraham Lincoln Print

The print features a black and white bust portrait of Abraham Lincoln that is similar to Anthony Berger\u27s 1864 portrait photograph (Ostendorf-92). To the portrait\u27s right, a quotation attributed to Lincoln appears. The print was originally enclosed in a rectangular frame held together by taped edges. However, the tape has disintegrated, leaving the framed work in pieces. Thus, the print was removed for preservation, but the frame was retained for its documentary significance.https://scholarsjunction.msstate.edu/fvw-artifacts/4043/thumbnail.jp

Effect of thermal phase fluctuations on the superfluid density of two-dimensional superconducting films

High precision measurements of the complex sheet conductivity of superconducting Mo77Ge23 thin films have been made from 0.4 K through Tc. A sharp drop in the inverse sheet inductance, 1/L(T), is observed at a temperature, Tc, which lies below the mean-field transition temperature, Tco. Just below Tc, the suppression of 1/L(T) below its mean-field value indicates that longitudinal phase fluctuations have nearly their full classical amplitude, but they disappear rapidly as T decreases. We argue that there is a quantum crossover at about 0.94 Tco, below which classical phase fluctuations are suppressed.Comment: 14 pages, 3 figures. Subm. to PR

On religion and cultural policy: notes on the Roman Catholic Church

This paper argues that religious institutions have largely been neglected within the study of cultural policy. This is attributed to the inherently secular tendency of most modern social sciences. Despite the predominance of the ‘secularisation paradigm’, the paper notes that religion continues to promote powerful attachments and denunciations. Arguments between the ‘new atheists’, in particular, Richard Dawkins, and their opponents are discussed, as is Habermas’s conciliatory encounter with Joseph Ratzinger (later Pope Benedict XVI). The paper then moves to a consideration of the Roman Catholic Church as an agent of cultural policy, whose overriding aim is the promotion of ‘Christian consciousness’. Discussion focuses on the contested meanings of this, with reference to (1) the deliberations of Vatican II and (2) the exercise of theological and cultural authority by the Pope and the Congregation for the Doctrine of the Faith (CDF). It is argued that these doctrinal disputes intersect with secular notions of social and cultural policy and warrant attention outside the specialist realm of theological discourse

Expression of paramyxovirus V proteins promotes replication and spread of hepatitis C virus in cultures of primary human fetal liver cells

Here we demonstrate that primary cultures of human fetal liver cells (HFLC) reliably support infection with laboratory strains of hepatitis C virus (HCV), although levels of virus replication vary significantly between different donor cell preparations and frequently decline in a manner suggestive of active viral clearance. To investigate possible contributions of the interferon (IFN) system to control HCV infection in HFLC, we exploited the well-characterized ability of paramyxovirus (PMV) V proteins to counteract both IFN induction and antiviral signaling. The V proteins of measles virus (MV) and parainfluenza virus 5 (PIV5) were introduced into HFLC using lentiviral vectors encoding a fluorescent reporter for visualization of HCV-infected cells. V protein-transduced HFLC supported enhanced (10 to 100-fold) levels of HCV infection relative to untransduced or control vector-transduced HFLC. Infection was assessed by measurement of virus-driven luciferase, by assays for infectious HCV and viral RNA, and by direct visualization of HCV-infected hepatocytes. Live cell imaging between 48 and 119 hours postinfection demonstrated little or no spread of infection in the absence of PMV V protein expression. In contrast, V protein-transduced HFLC showed numerous HCV infection events. V protein expression efficiently antagonized the HCV-inhibitory effects of added IFNs in HFLC. In addition, induction of the type III IFN, IL29, following acute HCV infection was inhibited in V protein-transduced cultures. Conclusion: These studies suggest that the cellular IFN response plays a significant role in limiting the spread of HCV infection in primary hepatocyte cultures. Strategies aimed at dampening this response may be key to further development of robust HCV culture systems, enabling studies of virus pathogenicity and the mechanisms by which HCV spreads in its natural host cell population.National Institutes of Health (U.S.) (NIH Roadmap for Medical Research Grant 1 R01 DK085713-01)Greenberg Institute for Medical ResearchStarr Foundatio

β-D-N4-hydroxycytidine (NHC) Inhibits SARS-CoV-2 Through Lethal Mutagenesis But Is Also Mutagenic To Mammalian Cells

Mutagenic ribonucleosides can act as broad-based antiviral agents. They are metabolized to the active ribonucleoside triphosphate form and concentrate in the genomes of RNA viruses during viral replication. β-D-N 4-hydroxycytidine (NHC, the initial metabolite of molnupiravir) is more than 100-fold more active than ribavirin or favipiravir against SARS-CoV-2, with antiviral activity correlated to the level of mutagenesis in virion RNA. However, NHC also displays host mutational activity in an animal cell culture assay, consistent with RNA and DNA precursors sharing a common intermediate of a ribonucleoside diphosphate. These results indicate that highly active mutagenic ribonucleosides may hold risk for the host

A critical review of the formation of mono- and dicarboxylated metabolic intermediates of alkylphenol polyethoxylates during wastewater treatment and their environmental significance

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2010 Taylor & Francis.Alkylphenoxyacetic acids, the metabolic biodegradation products of alkylphenol ethoxylates, are commonly found in wastewaters and sewage effluents. These persistent hydrophilic derivatives possess intrinsic estrogenic activity, which can mimic natural hormones. Their concentrations increase through the sewage treatment works as a result of biodegradation and biotransformation, and when discharged can disrupt endocrine function in fish. These acidic metabolites represent the dominant alkylphenolic compounds found in wastewater effluent and their presence is cause for concern as, potentially, through further biotransformation and biodegradation, they can act as sources of nonylphenol, which is toxic and estrogenic. The authors aim to assess the mechanisms of formation as well as elimination of alkylphenoxyacetic acids within conventional sewage treatment works with the emphasis on the activated sludge process. In addition, they evaluate the various factors influencing their degradation and formation in laboratory scale and full-scale systems. The environmental implications of these compounds are considered, as is the need for tertiary treatment processes for their removal

Use of a differential pressure transducer for the monitoring of soil volume change in cyclic triaxial test on unsaturated soils

A new experimental set-up using a differential pressure transducer was developed, that enables the monitoring of volume changes in cyclic triaxial tests on unsaturated soils. Calibration tests were performed in order to analyze the performance of the set-up, especially in terms of loading frequencies. Based on calibration results, a low frequency of 0.05 Hz was adopted for the tests carried out on the unsaturated loess from northern France. Five water contents were considered in the tests. The obtained results have confirmed the efficiency of the new system for volume change monitoring under cyclic loading. The effect of water content on the cyclic behavior of loess was clearly evidenced. Finally, some suggestions were made to improve the accuracy of the system

Escape from human monoclonal antibody neutralization affects in vitro and in vivo fitness of severe acute respiratory syndrome coronavirus

Background. Severe acute respiratory syndrome (SARS) emerged as a human disease in 2002. Detailed phylogenetic analysis and epidemiologic studies have suggested that the SARS Coronavirus (SARS-CoV) originated from animals. The spike (S) glycoprotein has been identified as a major target of protective immunity and contains ≥3 regions that are targeted by neutralizing antibodies in the S1 and S2 domains. We previously characterized a panel of neutralizing human monoclonal antibodies (MAbs), but the majority of epitopes recognized by the MAbs remain unknown. Methods. In the present study, we generated neutralization escape mutants and studied the effect of these neutralization escape mutations on human and animal receptor usage as well as on in vitro and in vivo fitness. Results. Distinct but partially overlapping sets of amino acids were identified that are critical to the binding of MAbs with differential neutralization profiles. We also identified possible interactions between the S1 and S2 domains of the SARS-CoV S glycoprotein. Finally, we showed that escape from neutralization usually attenuates SARS-CoV infection. Conclusions. These data provide a mechanism for overcoming neutralization escape by use of broadly crossreactive cocktails of cross-neutralizing MAbs that recognize residues within the receptor-binding domain that are critical for virus replication and virulence

TGFbeta induces apoptosis and EMT in primary mouse hepatocytes independently of p53, p21Cip1 or Rb status

Melville Trust for the Care and Cure of Cancer to SP and SS.Background: TGF beta has pleiotropic effects that range from regulation of proliferation and apoptosis to morphological changes and epithelial-mesenchymal transition (EMT). Some evidence suggests that these effects may be interconnected. We have recently reported that P53, P21(Cip1) and pRB, three critical regulators of the G1/S transition are variably involved in TGF beta-induced cell cycle arrest in hepatocytes. As these proteins are also involved in the regulation of apoptosis in many circumstances, we investigated their contribution to other relevant TGF beta-induced effects, namely apoptosis and EMT, and examined how the various processes were interrelated. Methods: Primary mouse hepatocytes deficient in p53, p21 and/or Rb, singly or in combination were treated with TGF beta for 24 to 96 hours. Apoptosis was quantified according to morphology and by immunostaining for cleavedcapsase 3. Epithelial and mesenchymal marker expression was studied using immunocytochemistry and real time PCR. Results: We found that TGF beta similarly induced morphological changes regardless of genotype and independently of proliferation index or sensitivity to inhibition of proliferation by TGF beta. Morphological changes were accompanied by decrease in E-cadherin and increased Snail expression but the mesenchymal markers (N-cadherin, SMA alpha and Vimentin) studied remained unchanged. TGF beta induced high levels of apoptosis in p53-/-, Rb-/-, p21(cip1)-/- and control hepatocytes although with slight differences in kinetics. This was unrelated to proliferation or changes in morphology and loss of cell-cell adhesion. However, hepatocytes deficient in both p53 and p21(cip1)were less sensitive to TGF beta-induced apoptosis. Conclusion: Although p53, p21(Cip1) and pRb are well known regulators of both proliferation and apoptosis in response to a multitude of stresses, we conclude that they are critical for TGF beta-driven inhibition of hepatocytes proliferation, but only slightly modulate TGF beta-induced apoptosis. This effect may depend on other parameters such as proliferation and the presence of other regulatory proteins as suggested by the consequences of p53, p21(Cip1) double deficiency. Similarly, p53, p21(Cip1) and pRB deficiency had no effect on the morphological changes and loss of cell adhesion which is thought to be critical for metastasis. This indicates that possible association of these genes with metastasis potential would be unlikely to involve TGF beta-induced EMT.Publisher PDFPeer reviewe

Deficiency of G1 regulators P53, P21Cip1 and/or pRb decreases hepatocyte sensitivity to TGFβ cell cycle arrest

<p>Abstract</p> <p>Background</p> <p>TGFβ is critical to control hepatocyte proliferation by inducing G1-growth arrest through multiple pathways leading to inhibition of E2F transcription activity. The retinoblastoma protein pRb is a key controller of E2F activity and G1/S transition which can be inhibited in viral hepatitis. It is not known whether the impairment of pRb would alter the growth inhibitory potential of TGFβ in disease. We asked how <it>Rb</it>-deficiency would affect responses to TGFβ-induced cell cycle arrest.</p> <p>Results</p> <p>Primary hepatocytes isolated from <it>Rb-floxed </it>mice were infected with an adenovirus expressing CRE-recombinase to delete the <it>Rb </it>gene. In control cells treatment with TGFβ prevented cells to enter S phase via decreased cMYC activity, activation of P16^INK4Aand P21^Cipand reduction of E2F activity. In <it>Rb</it>-null hepatocytes, cMYC activity decreased slightly but P16^INK4Awas not activated and the great majority of cells continued cycling. <it>Rb </it>is therefore central to TGFβ-induced cell cycle arrest in hepatocytes. However some <it>Rb</it>-null hepatocytes remained sensitive to TGFβ-induced cell cycle arrest. As these hepatocytes expressed very high levels of P21^Cip1and P53 we investigated whether these proteins regulate pRb-independent signaling to cell cycle arrest by evaluating the consequences of disruption of <it>p53 </it>and <it>p21</it>^{<it>Cip1</it>}. Hepatocytes deficient in <it>p53 or p21</it>^{<it>Cip1 </it>}showed diminished growth inhibition by TGFβ. Double deficiency had a similar impact showing that in cells containing functional pRb; P21^Cipand P53 work through the same pathway to regulate G1/S in response to TGFβ. In <it>Rb</it>-deficient cells however, <it>p53 </it>but not <it>p21</it>^{<it>Cip </it>}deficiency had an additive effect highlighting a pRb-independent-P53-dependent effector pathway of inhibition of E2F activity.</p> <p>Conclusion</p> <p>The present results show that otherwise genetically normal hepatocytes with disabled <it>p53</it>, <it>p21</it>^{<it>Cip1 </it>}or <it>Rb </it>genes respond less well to the antiproliferative effects of TGFβ. As the function of these critical cellular proteins can be impaired by common causes of chronic liver disease and HCC, including viral hepatitis B and C proteins, we suggest that disruption of pRb function, and to a lesser extend P21^Cip1and P53 in hepatocytes may represent an additional new mechanism of escape from TGFβ-growth-inhibition in the inflammatory milieu of chronic liver disease and contribute to cancer development.</p