Miracle-dz/UniFAR-FTUs huggingface dataset:
Initial HIV-1 Antigen-Specific CD8+ T Cells in Acute HIV-1 Infection Inhibit Transmitted/Founder Virus Replication

ABSTRACT CD8-mediated virus inhibition can be detected in HIV-1-positive subjects who naturally control virus replication. Characterizing the inhibitory function of CD8+ T cells during acute HIV-1 infection (AHI) can elucidate the nature of the CD8+ responses that can be rapidly elicited and that contribute to virus control. We examined the timing and HIV-1 antigen specificity of antiviral CD8+ T cells during AHI. Autologous and heterologous CD8+ T cell antiviral functions were assessed longitudinally during AHI in five donors from the CHAVI 001 cohort using a CD8+ T cell-mediated virus inhibition assay (CD8 VIA) and transmitted/founder (T/F) viruses. Potent CD8+ antiviral responses against heterologous T/F viruses appeared during AHI at the first time point sampled in each of the 5 donors (Fiebig stages 1/2 to 5). Inhibition of an autologous T/F virus was durable to 48 weeks; however, inhibition of heterologous responses declined concurrent with the resolution of viremia. HIV-1 viruses from 6 months postinfection were more resistant to CD8+-mediated virus inhibition than cognate T/F viruses, demonstrating that the virus escapes early from CD8+ T cell-mediated inhibition of virus replication. CD8+ T cell antigen-specific subsets mediated inhibition of T/F virus replication via soluble components, and these soluble responses were stimulated by peptide pools that include epitopes that were shown to drive HIV-1 escape during AHI. These data provide insights into the mechanisms of CD8-mediated virus inhibition and suggest that functional analyses will be important for determining whether similar antigen-specific virus inhibition can be induced by T cell-directed vaccine strategies.
Yb:YAG absorption at ambient and cryogenic temperatures

We have performed absorption measurements and generated absorption cross sections as a function of wavelength for the laser material YAG doped with ytterbium at 300, 175, and 75 K. This data was generated to enable a direct comparison of the absorption intensity and linewidths at room and cryogenic temperatures, and in particular near the temperature of liquid nitrogen at 77 K. The data have been used to compute universal absorption contour plots that display absorption as a function of the incident light center wavelength and optical thickness (doping density times penetration depth) for a number of bandwidths, and assuming that the spectrum of the incident light can be described as a Gaussian. Curves are presented for both 300 and 75 K, and may be used to optimize the absorption and laser efficiency.
Morphologic and Management Characteristics of Individuals with Unilateral Cleft Lip and Palate Who Required Maxillary Advancement

Objective: To delineate factors that may contribute to maxillary hypoplasia requiring maxillary advancement surgery in individuals with nonsyndromic unilateral cleft lip and palate (UCLP). Methods: This retrospective, longitudinal study used lateral cephalometric radiographs and chart reviews of 16 nonsyndromic UCLP individuals who underwent Le Fort I maxillary advancement and 16 controls matched for cleft type, age, and gender. Cephalometric measurements were made at three time points (T1, T2, and T3): mean ages of 10.7, 13.3, and 15.8 years for the Le Fort group and 10.11, 12.9, and 15.7 years, respectively, for the control group. Information regarding team care, timing and number of surgical procedures, and number of congenitally missing teeth were determined from clinical records. Results: The Le Fort group had significant maxillary hypoplasia at all time points compared to the UCLP controls, indicated by midface length measurements, ANB and Wit's analysis (p < .001). The Le Fort group had twice the number of palatal surgical procedures and number of missing teeth in the maxillary arch as compared with the cleft controls. Most of the control group had consistent team care, while most of the surgical group did not. Conclusions: Maxillary hypoplasia that will require a Le Fort I advancement can be determined as early as age 10. Multiple missing maxillary teeth, secondary palate procedures including pharyngeal flaps, and inconsistent team care with delayed orthodontic intervention are contributing factors to maxillary underdevelopment.
Optimal Switching Transition-Based Voltage Balancing Method for Flying Capacitor Multilevel Converters

This paper proposes a voltage balancing method for flying capacitor multilevel converters based on phase-disposition pulse width modulation (PD-PWM) using optimal transitions between converter switching states. The optimal transitions between converter switching states are possible due to the converter states' redundancy and are decided with the continuous evaluation and minimization of a cost function. Simulation and experimental results verify the robustness of the proposed voltage balancing method against different load conditions. A significant reduction of the average switching frequency is achieved, when compared to the use of the optimal state voltage balancing method, where the optimal states are decided independently for each voltage level ignoring how transitions impact on the converter switching frequency. Moreover, the line-to-line output voltages are compared with the ones obtained with other modulation techniques in terms of total harmonic distortion values, and PD-PWM with the proposed voltage balancing method produces the best results.
Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning.

The primary neuroendocrine interface, hypothalamus and pituitary, together with adrenals, constitute the major axis responsible for the maintenance of homeostasis and the response to the perturbations in the environment. The gene expression profiling in the human hypothalamus-pituitary-adrenal axis was catalogued by generating a large amount of expressed sequence tags (ESTs), followed by bioinformatics analysis (http://www.chgc.sh.cn/ database). Totally, 25,973 sequences of good quality were obtained from 31,130 clones (83.4%) from cDNA libraries of the hypothalamus, pituitary, and adrenal glands. After eliminating 5,347 sequences corresponding to repetitive elements and mtDNA, 20,626 ESTs could be assembled into 9, 175 clusters (3,979, 3,074, and 4,116 clusters in hypothalamus, pituitary, and adrenal glands, respectively) when overlapping ESTs were integrated. Of these clusters, 2,777 (30.3%) corresponded to known genes, 4,165 (44.8%) to dbESTs, and 2,233 (24.3%) to novel ESTs. The gene expression profiles reflected well the functional characteristics of the three levels in the hypothalamus-pituitary-adrenal axis, because most of the 20 genes with highest expression showed statistical difference in terms of tissue distribution, including a group of tissue-specific functional markers. Meanwhile, some findings were made with regard to the physiology of the axis, and 200 full-length cDNAs of novel genes were cloned and sequenced. All of these data may contribute to the understanding of the neuroendocrine regulation of human life.
Low-Dose Sirolimus in Combination with Mycophenolate Mofetil Improves Kidney Graft Function Late after Renal Transplantation and Suggests Pharmacokinetic Interaction of Both Immunosuppressive Drugs

Aims: Chronic allograft nephropathy and/or calcineurin inhibitor toxicity are common problems after organ transplantation. The aim of this study was to examine the safety and efficacy of switching from a calcineurin inhibitor-based to a calcineurin inhibitor-free immunosuppressive regimen consisting of sirolimus and mycophenolate mofetil (MMF) late after renal transplantation. Methods: Kidney biopsies were performed in renal-transplanted patients with increasing serum creatinine levels at least 6 months after transplantation (mean time ± SD after renal transplantation: 76.4 ± 50.4 months). Patients with no signs of acute rejection were switched to MMF (500–2,000 mg/day) in combination with a low dose of sirolimus (1 mg/day). Renal function, serum chemistry, blood trough levels of sirolimus and MMF, and blood pressure were monitored. Results: 13 patients were investigated. During our observation period (mean observation time ± SD: 11.2 ± 5.9 months), an improvement in renal function was observed in 10/13 patients. In 3/13 patients, renal function deteriorated further and hemodialysis was initiated in 2 patients within the next 6 months. However, a serum creatinine concentration above 3.5 mg/dl was measured in 2 of those 3 patients prior to the switch of the immunosuppressive protocol. Administration of a low dosis of sirolimus (1 mg/day) led to relevant sirolimus (4.16 ± 1.85 ng/ml) and MMF blood trough levels (month 1: 6.8 ± 3.46; month 3: 4.67 ± 1.78 mg/l). The following adverse events were observed: borderline acute rejection (1/11 patients), anemia responding to higher dosage of erythropoietin (3/11), hyperlipidemia (1/11), and urinary tract infections (4/11). Conclusions: Low-dose sirolimus therapy in combination with concentration-adjusted MMF therapy leads to improvement of organ function late after renal transplantation. The follow-up of those patients should include assessments of blood cell counts, serum lipids and urinalysis to recognize the possible side effects.
Alefacept: a safety profile

Alefacept is a selective immunomodulating, antipsoriatic drug that blocks the LFA-3/CD2 interaction necessary for the activation and proliferation of memory effector T cells by binding to CD2 expressed on the T cell surface. Because the CD4+ count is reduced by alefacept, it is recommended that this count be monitored on a regular basis to ensure that it does not drop below 250 cells/μl. Few side effects have been related to the use of alefacept that differ from placebo even when CD4+ counts drop below 250 cells/μl. The side effects that have been reported are minor and include: headache, nasopharyngitis, rhinitis, influenza, upper respiratory tract infections, pruritus, arthralgias, fatigue, nausea, accidental injury and increases in liver enzymes. Serious infections and malignancies do not appear linked to the use of alefacept. The percentage of patients who developed antibodies against alefacept is very low. Alefacept is a very safe biological therapy for moderate-to-severe chronic plaque psoriasis with few side effects reported. The utility of checking CD4 counts while administering alefacept for 12 weeks appears minimal.
Cross-modal subspace learning for sketch-based image retrieval: A comparative study

Sketch-based image retrieval (SBIR) has become a prominent research topic in recent years due to the proliferation of touch screens. The problem is however very challenging for that photos and sketches are inherently modeled in different modalities. Photos are accurate (colored and textured) depictions of the real-world, whereas sketches are highly abstract (black and white) renderings often drawn from human memory. This naturally motivates us to study the effectiveness of various cross-modal retrieval methods in SBIR. However, to the best of our knowledge, all established cross-modal algorithms are designed to traverse the more conventional cross-modal gap of image and text, making their general applicableness to SBIR unclear. In this paper, we design a series of experiments to clearly illustrate circumstances under which cross-modal methods can be best utilized to solve the SBIR problem. More specifically, we choose six state-of-the-art cross-modal subspace learning approaches that were shown to work well on image-text and conduct extensive experiments on a recently released SBIR dataset. Finally, we present detailed comparative analysis of the experimental results and offer insights to benefit future research.
Topologic and connectional analysis of the dorsal thalamus of Triturus alpestris (Amphibia, Urodela, Salamandridae)

A morphological and connectional analysis was performed on the dorsal thalamus of the alpine newt, Triturus alpestris. We have used a graphic reconstruction technique for the evaluation of the connectional (HRP) data. On the basis of these reconstructions, we propose a subdivision of the salamandrid dorsal thalamus into subhabenular, anteroventral, and posterodorsal zones. Each of these zones is defined by its telencephalic projections (“ascending thalamofugal systems”). The posterodorsal zone projects to the striatum, the anteroventral zone to the pallium. The subhabenular zone projects to the subpallial telencephalon and to the tegmentum. This zonal subdivision allows a more detailed comparison of the salamandrid dorsal thalamic features with ranid dorsal thalamic structures. We compare our dorsal thalamic zones to the ones proposed by Herrick (J. Comp. Neurol. 62:239–261, '35, The Brain of the Tiger Salamander. Chicago: The University of Chicago Press, ′48). Furthermore, using the same reconstructive technique, we undertook an analysis of the spatial relations of various inputs to the salamandrid dorsal thalamus (“thalamopetal systems”) Besides the well‐known retinal inputs, we identified the tectum and the tegmentum as sources of inputs to the thalamus. We provide evidence that there is no extensive multi‐ or unimodal overlap of these thalamopetal systems.
Transcriptional profiling reveals regulated genes in the hippocampus during memory formation

Transcriptional profiling (TP) offers a powerful approach to identify genes activated during memory formation and, by inference, the molecular pathways involved. Trace eyeblink conditioning is well suited for the study of regional gene expression because it requires the hippocampus, whereas the highly parallel task, delay conditioning, does not. First, we determined when gene expression was most regulated during trace conditioning. Rats were exposed to 200 trials per day of paired and unpaired stimuli each day for 4 days. Changes in gene expression were most apparent 24 h after exposure to 200 trials. Therefore, we profiled gene expression in the hippocampus 24 h after 200 trials of trace eyeblink conditioning, on multiple arrays using additional animals. Of 1,186 genes on the filter array, seven genes met the statistical criteria and were also validated by real‐time polymerase chain reaction. These genes were growth hormone (GH), c‐kit receptor tyrosine kinase (c‐kit), glutamate receptor, metabotropic 5 (mGluR5), nerve growth factor‐β (NGF‐β), Jun oncogene (c‐Jun), transmembrane receptor Unc5H1 (UNC5H1), and transmembrane receptor Unc5H2 (UNC5H2). All these genes, except for GH, were downregulated in response to trace conditioning. GH was upregulated; therefore, we also validated the downregulation of the GH inhibitor, somatostatin (SST), even though it just failed to meet criteria on the arrays. By during situ hybridization, GH was expressed throughout the cell layers of the hippocampus in response to trace conditioning. None of the genes regulated in trace eyeblink conditioning were similarly affected by delay conditioning, a task that does not require the hippocampus. These findings demonstrate that transcriptional profiling can exhibit a repertoire of genes sensitive to the formation of hippocampal‐dependent associative memories. Hippocampus 2002;12:821–833. © 2002 Wiley‐Liss, Inc.
Costs and cost-effectiveness of tuberculosis cultures using solid and liquid media in a developing country.

SETTING The expansion of culture has been proposed to aid tuberculosis (TB) control in developing countries. OBJECTIVES To examine the cost and cost-effectiveness at the Zambian National TB Reference Laboratory of homemade and commercially produced Löwenstein-Jensen culture (HLJ and CLJ) as well as automated and manually read liquid culture (AMGIT and MMGIT). DESIGN Costs were estimated from the provider's perspective and based on the average monthly throughput. Cost-effectiveness estimates were based on yield during the study period. RESULTS All techniques show comparable costs per culture (between US$28 and $32). Costs per Mycobacterium tuberculosis specimen detected were respectively US$197, $202, $312 and $340 for MMGIT, AMGIT, CLJ and HLJ. When modelled for the maximum throughput, costs were above US$95 per M. tuberculosis specimen detected for all techniques. When only performed among smear-negative specimens, costs per additionally identified M. tuberculosis would be US$487 for MMGIT and higher for other methods. CONCLUSION Based on cost-effectiveness grounds, liquid media compare well with conventional solid media, especially where yield of MGIT is substantially higher than that of LJ media. The results indicate high overall costs per culture; the expansion of culture to decentralised levels with lower throughputs may result in even higher costs.
A philosophical analysis of the Hill criteria

The epidemiological literature contains an ongoing and diversified discussion of the Hill criteria. This article offers a philosophical analysis of the criteria, showing that the criteria are related to two different views of causality. The authors argue that the criteria of strength, specificity, consistency, experiment, and biological gradient are related to a probabilistic regularity view of causality, whereas the criteria of coherence, plausibility, and analogy are related to a generative view of causality. The criterion of temporality is not related to either view, but may in contrast be central in inferring direction from cause to effect. The authors illuminate the aim and limitations of the various criteria that need to be included when discussing them.
Healthy Eating Strategies in the Workplace.

PURPOSE There is a clear link between dietary behavior and a range of chronic diseases, and overweight and obesity constitute an indirect risk in relation to these diseases. The worksite is a central venue for influencing dietary behavior. The purpose of this paper is to provide an overview of workplace influences on worker dietary patterns. DESIGN/METHODOLOGY/APPROACH The paper reviews the evidence of the effectiveness of dietary health promotion, and provides a brief overview of appropriate theoretical frameworks to guide intervention design and evaluation. The findings are illustrated through research examples. FINDINGS Through case studies and published research, it is found that workplace dietary interventions are generally effective, especially fruit and vegetable interventions. There is less consistent evidence on the long term effectiveness of workplace weight management interventions, underscoring the need for further research in this area. This paper also reports evidence that changes in the work environment, including through health and safety programs, may contribute to enhancing the effectiveness of workplace health promotion, including dietary interventions. Organizational factors such as work schedule may also influence dietary patterns. The social ecological model, the social contextual model and political process approach are presented as exemplar conceptual models that may be useful when designing or assessing the effects of workplace health promotion. ORIGINALITY/VALUE Using the worksite as setting for influencing health by influencing dietary patterns holds considerable promise and may be instrumental in reducing workers' risk of chronic diseases.
p300/CBP‐mediated p53 acetylation is commonly induced by p53‐activating agents and inhibited by MDM2

The tumor suppressor p53 is activated in response to many types of cellular and environmental insults via mechanisms involving post‐translational modification. Here we demonstrate that, unlike phosphorylation, p53 invariably undergoes acetylation in cells exposed to a variety of stress‐inducing agents including hypoxia, anti‐metabolites, nuclear export inhibitor and actinomycin D treatment. In vivo, p53 acetylation is mediated by the p300 and CBP acetyltransferases. Overexpression of either p300 or CBP, but not an acetyltransferase‐deficient mutant, efficiently induces specific p53 acetylation. In contrast, MDM2, a negative regulator of p53, actively suppresses p300/CBP‐mediated p53 acetylation in vivo and in vitro. This inhibitory activity of MDM2 on p53 acetylation is in turn abrogated by tumor suppressor p19ARF, indicating that regulation of acetylation is a central target of the p53–MDM2–p19ARF feedback loop. Functionally, inhibition of deacetylation promotes p53 stability, suggesting that acetylation plays a positive role in the accumulation of p53 protein in stress response. Our results provide evidence that p300/CBP‐mediated acetylation may be a universal and critical modifi cation for p53 function.
Interventions that effectively target Anopheles funestus mosquitoes could significantly improve control of persistent malaria transmission in south–eastern Tanzania

Malaria is transmitted by many Anopheles species whose proportionate contributions vary across settings. We re-assessed the roles of Anopheles arabiensis and Anopheles funestus, and examined potential benefits of species-specific interventions in an area in south-eastern Tanzania, where malaria transmission persists, four years after mass distribution of long-lasting insecticide-treated nets (LLINs). Monthly mosquito sampling was done in randomly selected households in three villages using CDC light traps and back-pack aspirators, between January-2015 and January-2016, four years after the last mass distribution of LLINs in 2011. Multiplex polymerase chain reaction (PCR) was used to identify members of An. funestus and Anopheles gambiae complexes. Enzyme-linked immunosorbent assay (ELISA) was used to detect Plasmodium sporozoites in mosquito salivary glands, and to identify sources of mosquito blood meals. WHO susceptibility assays were done on wild caught female An. funestus s.l, and physiological ages approximated by examining mosquito ovaries for parity. A total of 20,135 An. arabiensis and 4,759 An. funestus were collected. The An. funestus group consisted of 76.6% An. funestus s.s, 2.9% An. rivulorum, 7.1% An. leesoni, and 13.4% unamplified samples. Of all mosquitoes positive for Plasmodium, 82.6% were An. funestus s.s, 14.0% were An. arabiensis and 3.4% were An. rivulorum. An. funestus and An. arabiensis contributed 86.21% and 13.79% respectively, of annual entomological inoculation rate (EIR). An. arabiensis fed on humans (73.4%), cattle (22.0%), dogs (3.1%) and chicken (1.5%), but An. funestus fed exclusively on humans. The An. funestus populations were 100% susceptible to organophosphates, pirimiphos methyl and malathion, but resistant to permethrin (10.5% mortality), deltamethrin (18.7%), lambda-cyhalothrin (18.7%) and DDT (26.2%), and had reduced susceptibility to bendiocarb (95%) and propoxur (90.1%). Parity rate was higher in An. funestus (65.8%) than An. arabiensis (44.1%). Though An. arabiensis is still the most abundant vector species here, the remaining malaria transmission is predominantly mediated by An. funestus, possibly due to high insecticide resistance and high survival probabilities. Interventions that effectively target An. funestus mosquitoes could therefore significantly improve control of persistent malaria transmission in south–eastern Tanzania.