Miracle-dz/UniFAR-FTUs huggingface dataset:
Persistent Anti-Gag, -Nef, and -Rev IgM Levels as Markers of the Impaired Functions of CD4+ T-Helper Lymphocytes During SIVmac251 Infection of Cynomolgus Macaques

This study analyzed the antigen-specific (Gag, Nef, Rev, and Tat) IgM, IgG, and IgA humoral responses during the first 200 days of SIVmac251 infection in cynomolgus macaques. These responses were tested for correlation with the CD4+ T-cell-related hematologic parameters and viral load throughout the course of the study (acute and chronic infection, during and after antiretroviral therapy). Strong inverse correlations were observed between the percentage of CD4+ T cells at almost every timepoint of the study and the levels of IgM (but not IgG and IgA) against Gag, Nef, and Rev (but not Tat) measured after, but not during, the primary peak of IgM response. Significant levels of persistent antigen-specific IgMs may reflect the prevalence of mature plasma cells that have not undergone immunoglobulin class switching, possibly due to defects in helper T-cell function. Strong correlations were observed between the preinfection CD4+ T-cell count or CD4/CD8 ratio and the same parameters measured throughout the study, suggesting the importance of preinfection immune status as a determinant of disease progression. The negative correlations between the post-acute-phase IgM levels and the percentage of CD4+ T cells at later times during the study suggest the potential prognostic value of this measurement.
Structure, dynamics, and interactions of jacalin. Insights from molecular dynamics simulations examined in conjunction with results of X‐ray studies

Molecular dynamics simulations have been carried out on all the jacalin–carbohydrate complexes of known structure, models of unliganded molecules derived from the complexes and also models of relevant complexes where X‐ray structures are not available. Results of the simulations and the available crystal structures involving jacalin permit delineation of the relatively rigid and flexible regions of the molecule and the dynamical variability of the hydrogen bonds involved in stabilizing the structure. Local flexibility appears to be related to solvent accessibility. Hydrogen bonds involving side chains and water bridges involving buried water molecules appear to be important in the stabilization of loop structures. The lectin–carbohydrate interactions observed in crystal structures, the average parameters pertaining to them derived from simulations, energetic contribution of the stacking residue estimated from quantum mechanical calculations, and the scatter of the locations of carbohydrate and carbohydrate‐binding residues are consistent with the known thermodynamic parameters of jacalin–carbohydrate interactions. The simulations, along with X‐ray results, provide a fuller picture of carbohydrate binding by jacalin than provided by crystallographic analysis alone. The simulations confirm that in the unliganded structures water molecules tend to occupy the positions occupied by carbohydrate oxygens in the lectin–carbohydrate complexes. Population distributions in simulations of the free lectin, the ligands, and the complexes indicate a combination of conformational selection and induced fit. Proteins 2009. © 2009 Wiley‐Liss, Inc.
Theory as Fantasy: Emotional Dimensions to Grounded Theory

In this paper we discuss emotions and fantasies that inform and influence the project of theory building. Our argument is that theory building can be improved by engaging directly with emotions and with fantasies that are defensively and creatively generated by the researcher. Once acknowledged, these can be transformed into ideas and insights. We provide an example of the emotional dynamics surrounding a novice researcher's use of grounded theory within her doctoral research. We highlight three distinctive researcher fantasies of containment, coherence and purity associated with her experience of the method. We discuss how engagement with these fantasies deepened the researcher's analysis and thereby enhanced the process of building theory from the data. Therefore, our paper contributes to an understanding of how fantasies mobilized by such an open&#8208;ended research method can help to refine our thinking about emerging theory.
99mTc-HMPAO SPECT Study of Cerebral Perfusion After Treatment with Medication and Electroconvulsive Therapy in Major Depression

Compromised regional cerebral blood flow (rCBF) in major depressive disorder may be partly reversed by successful antidepressant treatment. However, it is not known if the reversal of rCBF compromise is dependant on the mode of antidepressant treatment. The current study aimed to address this question. Methods: Thirty-three patients (19 women and 14 men; mean age ± SD, 53 ± 16 y) with moderate major depressive disorder were studied before 6 wk of treatment with tricyclic antidepressants, selective serotonin reuptake inhibitors, or a course of electroconvulsive therapy, and 31 of these patients were also studied afterward. A comparison group of 25 healthy volunteers (13 women and 12 men; mean age, 49 ± 15 y) were studied once. rCBF was assessed using 99mTc-hexamethylpropyleneamine oxime SPECT. Images were analyzed using globally normalized statistical parametric mapping localized to the Montreal Neurologic Institute brain atlas. Results: Baseline rCBF was lower in depressed patients than in controls in the frontal cortex and subcortical nuclei bilaterally. A response to medication was associated with normalization of rCBF deficits, whereas a response to electroconvulsive therapy was associated with an additional rCBF decrease in the parietotemporal and cerebellar regions bilaterally. Conclusion: Hypoperfusion in major depressive disorder largely normalizes after a response to pharmacotherapy. Perfusion changes after a response to electroconvulsive therapy may follow a different course.
Chronomodulation of chemotherapy against metastatic colorectal cancer. International Organization for Cancer Chronotherapy.

Toxic effects of 5-fluorouracil (5-FU) and oxaliplatin (L-OHP), two active drugs against metastatic colorectal cancer, varied by 50% or more according to circadian dosing time in mice or rats. Adaptation of chemotherapy delivery to circadian rhythms (chronotherapy) was assessed in fully ambulatory outpatients, using multichannel programmable pumps. These devices allowed us to reliably test the clinical relevance of such a chronotherapy principle. First, single agent 5-day chronomodulated schedules were devised and assessed in Phase I and II trials with 5-fluorouracil (5-FU, peak delivery at 4:00 h) or oxaliplatin (L-OHP, peak at 16:00 h). Both schedules were then combined, folinic acid (FA) being added, synchronous with 5-FU infusion. This three-drug chronomodulated regimen (chrono-FFL) produced a 58% response rate (95% C.I.: 48-68%) in 93 patients with metastatic colorectal cancer, 46 of whom had previously received chemotherapy. In the first European randomised trial in 92 previously untreated patients, chronomodulated three-drug delivery achieved 53% response, as compared to 32% in those patients receiving flat infusion (P = 0.038). These respective figures were confirmed in a subsequent multicentre randomised trial involving 186 additional patients. Since the most active schedule was also the least toxic one by 2- to 10-fold, chrono-FFL was further intensified in three consecutive Phase II trials involving a total of 200 additional patients. Results suggest that both response rate and quality were further improved with such treatment intensification. Thus, chrono-FFL more than doubled the activity of chemotherapy against metastatic colorectal cancer in a multicentre European setting. (ABSTRACT TRUNCATED AT 250 WORDS)
Low Complication Rate Associated with Cesarean Section under Spinal Anesthesia for HIV-1–Infected Women on Antiretroviral Therapy

Background Elective cesarean section decreases the likelihood of vertical human immunodeficiency virus (HIV) transmission from mother to infant. This study aimed to determine whether cesarean section done with spinal anesthesia on HIV-1–infected pregnant women taking antiretroviral therapy is associated with intraoperative hemodynamic instability, postoperative complications, or changes in immune function or HIV-1 viral load. Methods A case-controlled study was conducted over a 3-year period in a London academic hospital. Forty-four women infected with HIV-1 and a control group of 45 HIV-negative women undergoing cesarean sections were included. The main outcome measures included intraoperative blood pressure, heart rate, blood loss, and ephedrine requirements, and postoperative infective complications, blood transfusion, changes in blood HIV-1 viral load and lymphocyte subsets, and time to hospital discharge. Results There were no differences in hemodynamic stability and postoperative complications between the HIV-infected group and the controls. There was an acute postoperative increase in the CD4T lymphocyte count (P = 0.01), but the CD4T:CD8T ratio and viral load did not change. Conclusions Elective cesarean section under spinal anesthesia for women infected with HIV-1 taking antiretroviral therapy was not associated with intraoperative or postoperative complications.
Cardiovascular effects of berberine in patients with severe congestive heart failure

Berberine, an alkaloid of the protoberberine family, has been shown to have strong positive inotropic and peripheral resistance‐lowering effects in dogs with and without heart failure. To determine the acute cardiovascular effects of berberine in humans, 12 patients with refractory congestive heart failure were studied before and during berberine intravenous infusion at rates of 0.02 and 0.2 mg/kg per min for 30 minutes. The lower infusion dose produced no significant circulatory changes, apart from a reduction in heart rate (14%). The 0.2 mg/kg per min dose elicited several significant changes: (a) Decreases in systemic (48%, p>0.01) and pulmonary vascular resistance (41%, p>0.01), and in right atrium (28%, p>0.05) and left ventricular end‐diastolic pressures (32%, p>0.01). (b) Increases in cardiac index (45%, p>0.01), stroke index (45%, p>0.01), and LV ejection fraction measured by contrast angiography (56%, p>0.01). (c) Increases in hemodynamic and echocardiographic indices of LV performance: peak measured velocity of shorten: ing (45%, p>0.01), peak shortening velocity at zero load (41%, p>0.01), rate of development of pressure at developed isovolumic pressure of 40 mmHg (20%, p>0.01), percent fractional shortening (50%, p>0.01), and the mean velocity of circumferential fiber shortening (54%, p>0.01). (d) Decrease of arteriovenous oxygen difference (28%, p>0.05) with no changes in total body oxygen uptake, arterial oxygen tension, or hemoglobin dissociation properties. These salutary acute effects show that berberine markedly improved cardiac performance in patients with heart failure refractory to conventional medical therapy with digitalis and diuretics. The improvement is probably subsequent to peripheral vasodilatation and to inotropic stimulation. Significant untoward effects appear to be the development of ventricular tachycardia with “torsades de pointes” morphology, detected in 4 patients 1‐20 h after the infusion of berberine. This possible association requires further elucidation before the administration of berberine may be extended to other patients in heart failure.
Volatility Risk Management of Chinese Stock Grading Market —An Empirical Study of GARCH-VaR Model

This paper mainly through the comparison of GARCH-VaR China stock market board, small board and gem in the United States correspond to the three stock index volatility, volatility between stock indexes obtained U.S. stock market volatility risk multi-level market differences. As a suggestion and reference for investors, it can also provide reference for the supervision department of stock market risk. Based on the empirical research, analyzes the advantages and disadvantages of traditional risk measurement methods, and combined with GARCH model with high degree of complexity and the practice effect analysis, trying to find the objective measure stock model analysis. In the specific study of the volatility of the stock market, through the comparison of China’s three major plates and the market classification mechanism of mature U. S. stock market, combined with the objective situation of the market, draw conclusions and change expectations. From the empirical results, the U.S. stock market has recovered after the financial crisis, and its performance on risk volatility is better than China’s three major plates. From the comparison of the stock market in the same country, the small and medium-sized plates tend to have greater risks, while the risks of the main board and the gem have the characteristics of low average value but frequent fluctuations.
Association between Hospital Birth Volume and Maternal Morbidity among Low-Risk Pregnancies in Rural, Urban, and Teaching Hospitals in the United States

Abstract Objectives This study aims to examine the relationship between hospital birth volume and multiple maternal morbidities among low-risk pregnancies in rural hospitals, urban non-teaching hospitals, and urban teaching hospitals, using a representative sample of U.S. hospitals. Study Design Using the 2011 Nationwide Inpatient Sample from 607 hospitals, we identified 508,146 obstetric deliveries meeting low-risk criteria and compared outcomes across hospital volume categories. Outcomes include postpartum hemorrhage (PPH), chorioamnionitis, endometritis, blood transfusion, severe perineal laceration, and wound infection. Results Hospital birth volume was more consistently related to PPH than to other maternal outcomes. Lowest-volume rural (< 200 births) and non-teaching (< 650 births) hospitals had 80% higher odds (adjusted odds ratio [AOR] = 1.80; 95% CI = 1.56–2.08) and 39% higher odds (AOR = 1.39; 95% CI = 1.26–1.53) of PPH respectively, than those in corresponding high-volume hospitals. However, in urban teaching hospitals, delivering in a lower-volume hospital was associated with 14% lower odds of PPH (AOR = 0.86; 95% CI = 0.80–0.93). Deliveries in rural hospitals had 31% higher odds of PPH than urban teaching hospitals (AOR = 1.31; 95% CI = 1.13–1.53). Conclusions Low birth volume was a risk factor for PPH in both rural and urban non-teaching hospitals, but not in urban teaching hospitals, where higher volume was associated with greater odds of PPH.
Where Did All the Unemployed Go? Non-standard work in Germany after the Hartz reforms

The number of unemployed workers in Germany decreased dramatically from its peak in February 2005 at over 5.2 million to 3.6 million by 2008. At the same time, employment increased by 1.2 million. Most theoretical and empirical analyses of this episode assume that a worker leaving unemployment moves into full employment. We ask where the unemployed actually went. Using and merging two large micro data sets, we account for the decrease of unemployment by computing inows and outows between unemployment and 16 other labour market states. Direct ows between unemployment and full employment contributed for only less than 9% to the decline in unemployment. By contrast, more than 37% of the unemployed workers ended up in non-standard work. About 13% participated in labour market policy programmes and 28% retired. Following the unemployment cohort of February 2005 over time conrms the order of magnitude of our ndings.
Loss of imprinting and cancer

Imprinting is defined as the parental allele‐specific expression of a very limited set of genes (about 50–80). This regulation depends upon an epigenetic marking of parental alleles during gametogenesis. Monoallelic expression ensures that the levels of the proteins encoded by imprinted genes, important factors of embryonic growth, placental growth or adult metabolism, are assured. Without precise control of their expression, developmental abnormalities result, as is shown by a number of hereditary over‐growth syndromes, including Beckwith–Wiedemann syndrome. The regulation of imprinted genes is largely dependent on methylation marks, which are laid down during embryological development of germ cells. Once in place, the methylation status of precise chromosomal regions, Imprinting Control Regions (ICRs), is read by either of two mechanisms, chromatin barrier formation or untranslated RNAs, thereby ensuring that only the maternal or paternal allele is expressed. Each imprinted gene is classified as maternal or paternal according to the expressed allele. The stability of the marked regions in somatic cells is maintained through each cellular replication by a methylation enzyme complex containing Dnmt1. Although the major reading mechanisms of imprinted status are known, chromatin boundary formation by CTCF and untranslated RNAs, the molecules elaborating the initial ICR methylation, are just being uncovered. Mis‐regulation of imprinted gene expression (loss of imprinting [LOI]) is seen frequently and precociously in a large variety of human tumours, making LOI a potentially valuable tool for both diagnosis and treatment. In fact, LOI is presently considered the most abundant and most precocious alteration in cancer. The present review proposes a mechanism responsible for LOI, as well as its eventual value in tumour diagnosis and prognosis. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
M-phase MELK activity is regulated by MPF and MAPK

Caroline Badouel, Roman Körner, Marie Frank-Vaillant, Anne Couturier, Erich A. Nigg and Jean-Pierre TassanThe protein kinase MELK is implicated in the control of cell proliferation, cell cycleand mRNA splicing. We previously showed that MELK activity is correlated with itsphosphorylation level, is cell cycle dependent, and maximal during mitosis. Here we report onthe identification of T414, T449, T451, T481 and S498 as residues phosphorylated inXenopus MELK (xMELK) in M-phase egg extract. Phosphorylations of T449, T451, T481are specifically detected during mitosis. Results obtained in vivo showed that MPF andMAPK pathways are involved in xMELK phosphorylation. In vitro, MPF and MAPK directlyphosphorylate xMELK and MPF phosphorylates xMELK on T481. In addition,phosphorylation by MPF and MAPK enhances MELK activity in vitro. Taken together ourresults indicate that MELK phosphorylation by MPF and MAPK enhance its activity duringM-phase.
Anti-TNF agents in Crohn’s disease

The current treatment of Crohn’s disease is limited by a lack of long-term efficacy of corticosteroid therapy and the associated side effects. Biological treatment strategies aimed at neutralising immune responses, offer new opportunities for the management of chronic inflammatory disorders. In Crohn’s disease, anti-TNF agents have taken the lead in development of immune-modulating drugs since TNF is known to be a pivotal cytokine in this illness. Different strategies have been explored aimed at inhibiting TNF but at present, the majority of clinical data have been obtained with monoclonal antihuman TNF antibodies. The chimeric anti-TNF IgG1 antibody infliximab (cA2, Remicade©, Centocor) has been proven, in multiple clinical trials, to be an effective and well tolerated therapy for the management of acute Crohn’s disease and recently this compound has obtained FDA and European Medicines Evaluation Agency approval. Although there are some concerns about immunogenicity of the anti-TNF antibody resulting in the formation of human antichimeric antibodies (HACA) as well as lymphoproliferative disorders, the clinical benefit in the treatment of refractory Crohn’s disease is a major therapeutic breakthrough. Further studies will be needed to establish the role and optimal dosing scheme of anti-TNF antibodies in maintenance of remission, monitor safety in the long run and to evaluate the effectiveness of alternative anti-TNF agents such as the TNF receptor/Fc fusion protein etanercept (Enbrel®, Immunex) and TNF synthesis inhibitor thalidomide.
How Are Lateral Chromatic Interactions Computed from Cone Signals?

A small gray test field superimposed on a large colored background appears tinted in a color complementary to that of the surround. We tested the hypothesis whether photoreceptor sensitivity in the test field is altered in the presence of a colored surround. We investigated this effect using dichoptic viewing conditions. With the left eye, subjects viewed a small gray target superimposed on a large colored background. The right eye saw a gray target superimposed on a large gray background. When the two images were fused, observers perceived one homogeneous background and two targets. Observers matched the color of the target seen by the right eye to that seen by the left eye. A modified two-stage model for chromatic induction assuming that both receptor and postreceptor mechanisms contribute to the shift in color was fitted to the matched settings. We find that the dichoptic viewing effects presented here are well explained by an approximately equal contribution of receptor and postreceptor processes to the perceived shift in color.
Expression of cardiac calcium regulatory proteins in atrium v ventricle in different species.

The duration of contraction in isolated electrically driven preparations from atrium and ventricle of mouse, rat, rabbit, guinea-pig and dog was consistently shorter in atrial compared to ventricular preparations. Overexpression of phospholamban (PLB) in transgenic mice prolonged duration of contraction, underscoring the importance of PLB for kinetics of cardiac contractility. The expression of regulatory proteins was studied by Western and Northern blot analysis. In rat myocardium, expression of the sarcoplasmic reticulum Ca2+ ATPase (SERCA) was higher in atrium than in ventricle, as was also observed in the rabbit, guinea-pig and wild-type mouse samples. Canine myocardium, however, had similar levels of SERCA (protein and mRNA) in atrium and ventricle. PLB and calsequestrin on protein and RNA levels were lower in atrium than in ventricle from rat, rabbit, guinea-pig and wild-type mouse. PLB protein and RNA levels were higher in ventricle than in atrium at ages 1 and 5 days postnatally and in adult rats. SERCA protein and RNA levels were higher in ventricle than in atrium at days 1 and 5 after birth, but lower in ventricle than in atrium in adult rats. In dog, the calsequestrin level was identical in atrium and ventricle (protein and mRNA) and PLB did not differ between atrium vs ventricle at the protein level but was lower at the mRNA level. Also, Ca2+ uptake was higher in atrium than in ventricle in the dog samples. The expression of the inhibitory subunit of troponin was unchanged between atrium and ventricle in all species studied (protein and mRNA). In dog, protein expression of triadin and junctin was lower in atrium vs ventricle. Triadin mRNA was not altered in dog atrium vs ventricle. In summary, while the hastened relaxation of atrium vs ventricle correlates in part with the lower expression of PLB and higher expression of SERCA, altered regional expression of other SR proteins handling Ca2+ may also play an important role in some species.