Miracle-dz/UniFAR-FTUs huggingface dataset:
Tracking replication-competent HIV reservoirs in infected individuals

Purpose of reviewProlonged suppression of plasma viremia is now achievable in a majority of HIV-infected individuals receiving antiretroviral therapy (ART). However, ART alone cannot eradicate HIV in infected individuals. The purpose of this review is to discuss the importance of tracking levels of infected CD4+ T cells carrying replication-competent HIV in basic and clinical research and how the use of this virologic marker could help determine the efficacy of ART and several novel therapeutic strategies that are being proposed for eliminating persistent viral reservoir in infected individuals receiving ART. Recent findingsIn recent years, there has been a growing interest within the HIV/AIDS scientific community to develop therapeutic strategies aimed at eliminating persistently infected CD4+ T cells in order to achieve a cure for HIV in infected individuals receiving ART. These approaches include administration of HIV-activating agents, modification of the genetics of CD4+ T cells, stem cell transplantation, and therapeutic vaccination. Such approaches would ultimately require careful and accurate assessments of the effect of therapeutic agents on HIV burden in infected individuals. SummaryGiven that the majority of infected CD4+ T cells in vivo carry replication-defective HIV, longitudinal measurements of the frequency of cells carrying replication-competent HIV along with other quantitative virologic parameters, such as levels of plasma viremia and cell-associated viral nucleic acid, can provide critical insight into the dynamics of the persistent viral reservoirs. Information related to HIV pathogenesis and the feasibility of eradicating the virus in infected individuals receiving ART in combination with novel therapeutic agents can also be gained from these analyses.
Drive and sense interface for gyroscopes based on bandpass sigma-delta modulators

This paper demonstrates a MEMS gyroscope system with extensive use of sigma-delta (ΣΔ) modulation in both, primary and secondary modes. The primary loop has a bandpass ΣΔ-digital-to-analog converter (DAC) driving the primary mass into resonance, which is implemented on a field programmable gate array (FPGA). With this strategy of shifting the primary oscillation control into the digital domain, the analog circuit complexity is enormously reduced. A continuous-time (CT) fourth-order micro-electro-mechanical ΣΔ Modulator (ΣΔM) incorporating the secondary resonator is used to convert the Coriolis rate signal into a bit stream. This ΣΔM is implemented on PCB performing an in-band noise (IBN) below −60 dBFS.
Small group learning in the final year of a medical degree: a quantitative and qualitative evaluation

The new undergraduate medical curriculum in Manchester uses problem-based learning (PBL) throughout the course. However, the major difference from other PBL schools is that in years 3 & 4 (phase 2) the students can use clinical experience when discussing the paper cases. The process is then developed further in year 5 (phase 3), in which there are no set PBL 'triggers' and students bring their own cases to the groups for discussion. In this study, we have explored what happens in the phase 3 (year 5) group sessions and how the students view them. A questionnaire and focus groups were used to generate data, from which a model was developed of what happens in a 'good' group session. The data suggest that most groups run on a case-presentation and discussion format, most commonly about clinical management and diagnosis. Students want tutors to act as an expert resource and to be flexible in allowing students to direct the discussions. University guidance about the group sessions was not generally used.
A comparison of four international surveys of tobacco dependence treatment provision: implications for monitoring the Framework Convention on Tobacco Control.

AIMS Article 14 of the Framework Convention on Tobacco Control (FCTC) requires countries to implement systems to provide tobacco dependence treatment. We report on global efforts to monitor the implementation of Article 14, and compare the surveys used in this effort. DESIGN Cross-sectional comparison of agreement (concordance and discordance) among the four main surveys used to monitor tobacco dependence treatment provision. SETTING Four global surveys of tobacco treatment provision. PARTICIPANTS The four surveys were Raw et al. (2009), the Framework Convention Alliance (FCA) Monitor, World Health Organization (WHO) MPOWER survey and the FCTC Party Reports. MEASUREMENTS Concordance as measured by percentage providing the same answers, as well as kappa statistic of inter-rater agreement. FINDINGS The four surveys used to monitor Article 14 implementation vary widely in countries sampled, questions asked, respondent characteristics and survey design. The four surveys generally show a moderate to high concordance (kappa > 0.60) with each other across most survey pairs and most domains, except for the MPOWER and FCTC Party governmental surveys (63% overall concordance, kappa =0.26). This concordance was lower than any other survey pair examined. Government respondents to the WHO MPOWER and FCTC Party Report surveys provided answers to the same question domains with relatively poorer concordance than those from surveys of non-governmental or mixed governmental/non-governmental sources. CONCLUSIONS Current surveys of tobacco dependence treatment provision are in general agreement with each other except for the two official government surveys that rely on governmental respondents. We believe that this points to the continued need for independent non-governmental monitoring of FCTC protocol implementation.
Successful eltrombopag treatment of severe refractory thrombocytopenia in chronic myelomonocytic leukemia

Rationale: Thrombocytopenia in chronic myelomonocytic leukemia (CMML) is usually attributed to impaired marrow production resulting from cytotoxic drug use or CMML itself (“CMML-induced thrombocytopenia”). In very rare cases, immune thrombocytopenia (ITP) can be a complication of CMML (“CMML-associated ITP”). However, treatment of severe thrombocytopenia in patients with CMML is still a challenge. Patient concerns: Case 1 was a 61-year-old female patient admitted to our hospital because of skin petechiae and purpura for 6 days. She had increased monocyte cell count (1.82 × 109/L), markedly decreased platelet count (2 × 109/L), hypercellularity of the megakaryocyte lineage with many immature megakaryocytes, and ZRSR2(zinc finger CCCH-type, RNA binding motif and serine/arginine rich 2) mutation. She failed to the treatment of corticosteroids, intravenous immunoglobulin (IVIg), TPO (thrombopoietin), and cyclosporin A (CsA). Case 2 was a 72-year-old female patient with thrombocytosis and monocytosis for 4 years, and thrombocytopenia for 6 months. After 10 courses of decitabine therapy, she had a persistent severe thrombocytopenia and decreased number of megakaryocytes, TET2 (tet methylcytosine dioxygenase 2) and SRSF2 (serine and arginine rich splicing factor 2) mutations were detected. She was dependent on platelet transfusion. Diagnoses: Case 1 was diagnosed as CMML-associated ITP, and case 2 as CMML with decitabine therapy-induced thrombocytopenia. Interventions: Both patients were treated with eltrombopag. Outcomes: In both patients, the platelet counts returned to the normal within 1 week after eltrombopag therapy. The platelet count in case 1 patient remained stable at 141–200 × 109/L for 20 months with stopping therapy for 3 months. In case 2 patient, eltrombopag was stopped 1 month later. Her platelet count decreased to 41 × 109/L, but was stable at ∼30 × 109/L for 3 months with platelet transfusion independency for 12 months. Both patients had no adverse effects with eltrombopag. Lessons: CMML-associated ITP is very rare and easily misdiagnosed. To the best of our knowledge, case 1 is the first reported case of the successful treatment of CMML-associated ITP with eltrombopag. Both CMML-associated ITP and decitabine therapy-induced thrombocytopenia in these 2 patients were highly sensitive and safe to eltrombopag therapy.
The Yellow Ribboning of the USA: Contested Meanings in the Construction of a Political Symbol

Durant la Guerre du Golfe, le fait d'arborer ou d'utiliser un ruban jaune aux Etats-Unis indiquait une position patriotique de soutien aux troupes mais pas forcement a la guerre. Cet article montre de multiples usages ou non-usages du ruban jaune ou de couleurs alternatives pour exprimer diverses positions. L'A. rappelle certains points comme le role joue par les femmes militaires, la presence d'homosexuels dans l'armee, ainsi que la sur-representation des Noirs et des classes defavorisees dans les troupes engagees dans le conflit. Une relation entre sexualite, masculinite et aggressivite guerriere est egalement analysee. L'A. montre que les voix s'inscrivant en dissonance par rapport au consensus apparent exprime par la pretendue « neutralite » du ruban jaune ont ete peu entendues et qu'aucune place n'a ete laissee pour un debat de fond sur la guerre elle-meme
Loss of NAD(P)-reducing power and glutathione disulfide excretion at the start of induction of aerial growth in Neurospora crassa

When exponentially growing hyphae of Neurospora crassa in aerated liquid cultures are filtered and the resulting mycelial mat is exposed to air, aerial hyphae develop and synchronous conidiation is obtained. The hyphae in direct contact with air adhere to each other within minutes and form aerial hyphae during the following 12 h; the hyphae which are not in direct contact with air do not adhere to each other and do not form aerial hyphae. Previous data indicated that oxidative stress was generated in the adhering hyphae; proteins and specific enzymes were found to be oxidatively modified and degraded. In this work, we report a dramatic fall in the reduced-to-oxidized ratio of NAD and NADP coenzymes during the first 6 min of exposure to air. This drop did not occur in a mycelial mat exposed to a N2-enriched atmosphere. Adding a carbon source to the mycelial mat did not abolish the loss of NAD(P)-reducing power. After the initial fall, the reducing levels of the coenzymes returned to the starting value in about 30 min. A peak of extracellular glutathione disulfide occurred simultaneously with the loss of NAD(P)-reducing power. The reducing power loss and the excretion of glutathione disulfide are thought to be consequences of a hyperoxidant state; the adhesion of hyphae is thought to be a response to the hyperoxidant state.
Composition de polyèdres associés aux problèmes d'optimisation combinatoire. (Composition of polyhedra and their relation to some combinatorial optimization problems)

Le polyedre associe a un probleme d'optimisation combinatoire est l'enveloppe convexe des (vecteurs d'incidence des) solutions realisables de ce probleme. De nombreux problemes d'optimisation combinatoire se formulent comme une maximisation de fonctions lineaires sur les polyedres qui leurs sont associes. La description du polyedre par un systeme d'inequations lineaires est intimement liee a la resolution du probleme correspondant, par le biais de la programmation lineaire. Afin de determiner un tel systeme, une approche classique consiste a decomposer le probleme en sous-problemes tels que les polyedres associes soient connus ; une composition ulterieure de ces derniers conduit a une description du polyedre associe au probleme considere. L'objet principal de cette these est l'etude de la composition des polyedres. Dans un premier temps, une approche de composition, basee sur la programmation dynamique et les methodes de projection polyedrale, est etudiee et des resultats generaux sont proposes, permettant ainsi d'unifier des recherches existantes dans ce domaine. Cette approche est, ensuite, appliquee a la composition de polyedres associes au probleme du voyageur de commerce. En seconde partie, considerant le probleme du stable, des operations sur les graphes (composition par identification de sous-graphes de deux graphes donnes, adjonction d'une nouvelle arete) sont traitees. Des resultats polyedraux sont donc donnes, et des consequences concernant la perfection et la h-perfection des graphes sont montres
Model-Based Indirect Learning Method Based on Dyna-Q Architecture

In this paper, a model learning method based on tree structures is present to achieve the sample efficiency in stochastic environment. The proposed method is composed of Q-Learning algorithm to form a Dyna agent that can used to speed up learning. The Q-Learning is used to learn the policy, and the proposed method is for model learning. The model builds the environment model and simulates the virtual experience. The virtual experience can decrease the interaction between the agent and the environment and make the agent perform value iterations quickly. Thus, the proposed agent has additional experience for updating the policy. The simulation task, a mobile robot in a maze, is introduced to compare the methods, Q-Learning, Dyna-Q and the proposed method. The result of simulation confirms the proposed method that can achieve the goal of sample efficiency.
Immunological and Virological Changes in Antiretroviral Naïve Human Immunodeficiency Virus Infected Patients Randomized to G‐CSF or Placebo Simultaneously with Initiation of HAART

To determine the efficacy of combined G‐CSF and highly active antiretroviral treatment (HAART), a randomized, double blind, placebo controlled study was conducted. Treatment naive human immunodeficiency virus (HIV) infected patients were randomized to receive either placebo or G‐CSF (0.3 mg/ml, 3 times a week) for 12 weeks and HAART simultaneously. The trial was terminated prematurely after interim analysis performed because of a case of severe encephalopathia in the G‐CSF group. At that point 11 HIV infected patients with a CD4+ T cell count < 350/mm3 had been randomized to the G‐CSF group (n = 6) or placebo group (n = 5). In both groups plasma HIV RNA decreased significantly in response to HAART. However, plasma HIV RNA changed significantly different between the two groups with the decrease being less pronounced in the G‐CSF group (P = 0.02). The concentrations of CD4+ memory T cells and CD8+ naive and memory T cells increased in response to HAART, and there was a trend towards more pronounced increases in several T‐cell subpopulations in the G‐CSF group. The CD56+ NK cells increased significantly more in the G‐CSF group compared with placebo (P = 0.000). All patients in the G‐CSF group reported bone pain. The present data do not support simultaneous administration of G‐CSF with initiation of HAART in treatment naive HIV infected patients.
Ischaemic stroke in patients with atrial fibrillation with chronic kidney disease undergoing peritoneal dialysis.

AIMS Little is known about the ischaemic stroke risk and benefit of warfarin therapy for stroke prevention in chronic kidney disease (CKD) patients on peritoneal dialysis (PD) with concomitant atrial fibrillation (AF). Our objective was to determine the risk of ischaemic stroke in a 'real-world' cohort of PD patients with AF, and clinical benefit or harm of aspirin and warfarin. METHODS AND RESULTS This is a single-centred observational study of Chinese patients with non-valvular AF. Hospitalizations with ischaemic stroke and intracranial haemorrhage (ICH) were recorded. Of 9810 patients from a hospital-based AF registry, 271 CKD patients on PD with AF (76.8 ± 12.5 years, CHA2DS2-VASc: 3.69 ± 1.83, and HAS-BLED: 2.07 ± 0.97) were identified. Amongst these PD patients, 24.7% received warfarin; 31.7% received aspirin; and 43.5% received no antithrombotic therapy. Amongst patients with no antithrombotic therapy, annual incidence of ischaemic stroke in PD patients was comparable with those non-CKD counterparts (9.32 vs. 9.30%/year). Similar to non-CKD patients, annual incidence of ischaemic stroke increased with increasing CHA2DS2-VASc score (CHA2DS2-VASc = 0-1: 5.76 vs. 5.70%/year, P = 1.00; and CHA2DS2-VASc ≥ 2: 10.80 vs. 9.94%/year, P = 0.78). Amongst PD patients, warfarin therapy was associated with lower risk of ischaemic stroke compared with aspirin [Hazard ratio (HR): 0.16, 95% confidence interval (CI): 0.04-0.66, P = 0.01] and no therapy (HR: 0.19, 95% CI: 0.06-0.65, P = 0.01), but not associated with a higher risk of ICH. CONCLUSION In CKD patients on PD with AF, who had similar ischaemic stroke risk as non-CKD counterparts, warfarin therapy is associated with reduction in risk of ischaemic stroke without a higher risk of ICH.
Polarization and Rising Wage Inequality: Comparing the U.S. And Germany

This paper compares trends in wage inequality in the U.S. and Germany using an approach developed by MaCurdy and Mroz (1995) to separate age, time, and cohort effects. Between 1979 and 2004, wage inequality increased strongly in both the U.S. and Germany but there were various country specific aspects of this increase. For the U.S., we find faster wage growth since the 1990s at the top (80% quantile) and the bottom (20% quantile) compared to the median of the wage distribution, which is evidence for polarization in the U.S. labor market. In contrast, we find little evidence for wage polarization in Germany. Moreover, we see a large role played by cohort effects in Germany, while we find only small cohort effects in the U.S. Employment trends in both countries are consistent with polarization since the 1990s. We conclude that although there is evidence in both the U.S. and Germany which is consistent with a technology-driven polarization of the labor market, the patterns of trends in wage inequality differ strongly enough that technology effects alone cannot explain the empirical findings.
Isolation of Methoxyfuranocoumarins From Ammi majus by Centrifugal Partition Chromatography.

Pure methoxyfuranocoumarins were isolated from Ammi majus L. by use of low-pressure column chromatography (LPCC) followed by centrifugal partition chromatography (CPC). The concentrated petroleum ether extract from fruits of A. majus was fractionated on a silica gel column using a gradient of ethyl acetate in dichloromethane (0-80%, v/v). Coumarin-rich fractions were analyzed by thin-layer chromatography (TLC) and high-performance liquid chromatography with diode array detection (HPLC/DAD). Xanthotoxin (8-MOP) and isopimpinellin (isoP), structurally similar compounds, were isolated in one fraction (FR6). To avoid multistep and long-lasting TLC preparation, optimization of CPC conditions has been performed. In one run, an effective separation of 8-MOP and isoP was achieved. The two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (10 : 8 : 10 : 9; v/v) in an ascending mode (the aqueous phase was a stationary phase, and the organic phase was a mobile phase), with flow rate 3 mL/min and rotation speed 1,600 r.p.m. , was used. The identification and high purities of isolated 8-MOP (98.7%) and isoP (100%) were confirmed by HPLC/DAD assay, when compared with standards. The developed CPC method could be applied to the effective isolation of 8-MOP and isoP from plant extracts. The high purity of obtained compounds makes possible further exploitation of these components in biological studies.
Isolation and Characterization of a Dual Prenylated Rab and VAMP2 Receptor*

Rab GTPases have been implicated in intracellular vesicle trafficking. Using the yeast two-hybrid screen, we have isolated a rat clone that interacts with Rab3A as well as with Rab1. The gene encodes a 20.6-kDa protein with two extensive hydrophobic domains and is broadly expressed in all tissues. This protein binds to prenylated Rab GTPases but not to other small Ras-like GTPases such as the Rho/Rac family. This prenylated Rab acceptor (PRA1) also binds specifically to the synaptic vesicle protein VAMP2 (or synaptobrevin II) but shows no affinity for VAMP1 or cellubrevin in both the yeast two-hybrid system and in vitro binding assays. This specificity resides, in part, in the proline-rich domain of VAMP2 as a chimera containing this domain of VAMP2 fused to VAMP1 is able to bind to PRA1. The transmembrane domain of VAMP2 is also essential as its deletion abolished binding to PRA1. Replacement of the deleted VAMP2 transmembrane domain by a CAAX prenylation signal can not restore binding to PRA1. This interaction is therefore distinct from that required for VAMP2 binding to either syntaxin or both syntaxin and SNAP-25. Deletion analysis on PRA1 indicates that the critical Rab- and VAMP2-interacting residues reside in two regions: the amino-terminal residues 30–54 and the extreme carboxyl-terminal domain. This dual Rab and VAMP2 binding characteristic suggests that PRA1 may serve to link these two protein families in the control of vesicle docking and fusion.
A prospective study of plasma prolactin levels and subsequent risk of breast cancer

Plasma prolactin was measured in 2,572 premenopausal, 628 menopausal, and 1,666 peri‐ and postmenopausal women who were apparently healthy. Breast cancer was subsequently diagnosed in 47 of these women at a median time of 5 years after blood collection (pre‐cancer cases). Prolactin levels in pre‐menopausal cases increased significantly with age whereas this was not found in matched controls. The perimenopausal cases were characterized by extreme variability in prolactin levels. In post‐menopausal women who developed breast cancer, the prolactin levels were significantly elevated, being at or above the 70th percentile for the controls. In this group the results are consistent with prolactin acting as a late‐stage tumour promoter.
Plasma leptin and adiponectin concentrations correlate with cardiometabolic risk and systemic inflammation in healthy, non-obese children

Abstract Background: Plasma adipocytokines are associated with metabolic profile and cardiovascular risk in obese children. Objective: To investigate the association of plasma leptin and adiponectin concentrations with cardiometabolic risk profile and systemic inflammation in non-obese children. Subjects: We studied 170 healthy, non-obese children (86 males, mean age 10±2 years). Methods: Children’s current body mass index (BMI), plasma leptin and adiponectin concentrations, lipid profile, fasting plasma glucose and high sensitivity C reactive protein (hsCRP) were measured. Results: After adjustment for age, gender and BMI, plasma leptin concentrations were positively associated with hsCRP (t=2.72, p=0.009) and fasting plasma glucose (t=4.27, p<0.0001); plasma adiponectin concentrations were negatively associated with hsCRP (t=–3.31, p=0.0016); and positively with high density lipoprotein cholesterol (t=2.32, p=0.02). Children in the highest quartile of leptin/adiponectin (L/A) ratio demonstrated significantly higher BMI, systolic blood pressure, hsCRP, triglycerides and fasting glucose and the lowest high density lipoprotein (HDL) compared to lower L/A ratio quartiles. Conclusions: Alterations in plasma leptin and adiponectin may help to reclassify non-obese children, detecting those with more unfavorable risk profiles independent of BMI status.