Miracle-dz/UniFAR-FTUs huggingface dataset:
Survival and Homeostasis Essential Role for CAML in Follicular B Cell

Calcium-modulating cyclophilin ligand (CAML) is a ubiquitously expressed protein that is important during thymopoiesis. How-ever, whether it serves a function in mature lymphocytes is unknown. In this article, we show that CAML is essential for survival of peripheral follicular (Fo) B cells. Conditional deletion of CAML in CD19-Cre transgenic mice caused a signiﬁcant reduction in Fo cell numbers and increased rates of homeostatic proliferation. CAML-deﬁcient Fo cells showed increased cellular turnover and normal proliferative ability. Although CAML-deﬁcient Fo cells responded to AgR stimulation and to B cell activating factor, they displayed decreased survival and increased apoptosis following stimulation with LPS and IL-4 in vitro. Failure to survive was not due to aberrant B cell development in the absence of CAML, because induced deletion of the gene in mature cells resulted in a similar phenotype. These data establish an essential and ongoing role for CAML in the long-term survival of mature B cells. The Journal of Immunology , 2012, 188: 000–000. lymphocytes play a critically important role in humoral immunity and may participate in regulation of cell-mediated immunity as well. In addition, malignancies of the B cell compartment make up a signiﬁcant fraction of childhood and adult hematologic malignancies. It is important, therefore, to understand the molecular mechanisms that regulate the development and function of these cells.
A Compact Model for Metal–Oxide Resistive Random Access Memory With Experiment Verification

A dynamic Verilog-A resistive random access memory (RRAM) compact model, including cycle-to-cycle variation, is developed for circuit/system explorations. The model not only captures dc and ac behavior, but also includes intrinsic random fluctuations and variations. A methodology to systematically calibrate the model parameters with experiments is presented and illustrated with a broad set of experimental data, including multilayer RRAM. The physical meanings of the various model parameters are discussed. An example of applying the RRAM cell model to a ternary content-addressable-memory (TCAM) macro is provided. Tradeoffs on the design of RRAM devices for the TCAM macro are discussed in the context of the energy consumption and worst case latency of the memory array.
Effects of soya milk and Bifidobacterium-fermented soya milk on plasma and liver lipids, and faecal steroids in hamsters fed on a cholesterol-free or cholesterol-enriched diet

The effects of freeze-dried soya milk (SM) and Bifidobacterium-fermented soya milk (FSM) on plasma and liver lipids, and faecal steroid excretion were estimated in hamsters fed on a cholesterol-free or cholesterol-enriched diet. Hamsters fed on the cholesterol-free diet containing 300 g FSM/kg had lower levels of plasma VLDL + LDL cholesterol than the animals fed on the control diet. SM in the diet produced a similar pattern without significant differences. In the cholesterol-enriched diet group, SM and FSM decreased the levels of plasma total cholesterol and VLDL + LDL-cholesterol. SM and FSM decreased the plasma triacylglycerol level in both the cholesterol-free and -enriched diet groups. The liver total cholesterol contents in the SM and FSM groups were lower than that in the control group, for hamsters fed on the cholesterol-free diet. The liver triacylglycerol content was not modified by SM or FSM in hamsters fed on either the cholesterol-free or -enriched diet. SM and FSM increased the total bile acid excretion and the proportion of cholesterol entering the cholic acid biosynthesis pathway in both the cholesterol-free and -enriched diet groups. SM and FSM did not affect neutral steroid excretion in the cholesterol-free or -enriched diet group. There was an inverse relationship between VLDL + LDL-cholesterol and faecal bile acid excretion in hamsters fed on the cholesterol-free (r −0.670, P < 0.01) and cholesterol-enriched (r −0.761, P < 0.001) diets respectively. These results indicated that SM had an anti-atherogenic effect, and that this effect was not diminished by prior fermentation.
Public's Inflation Expectations and Monetary Policy

The paper develops a DSGE model where monetary policy propagates by affecting and coordinating price setters' expectations. Price setters face costs of price adjustment and do not observe the history of technology, monetary, and preference shocks. They form expectations about the evolution of their nominal marginal costs observing their idiosyncratic productivity, which is correlated with the aggregate productivity, last period's output and inflation, and the interest rate set by the central bank according to a Taylor rule. The model is estimated through likelihood methods on a U.S. data set including the Survey of Professional Forecasters as a measure of price setters' expectations. The transmission channel based on price-setters' expectations is found to account for the following three empirical facts that have been documented by the VAR literature: (i) the delayed and persistent effects of monetary shocks on inflation with associated sluggish response of real output; (ii) the price puzzle; (iii) the disappearance of the price puzzle after the 1970s. Structural policies of disinflation, such as the introduction of an "inflation targeting", need to be backed up by a perfect commitment device to succeed.
High-performance nonlinear feedback control of a permanent magnet stepper motor

The permanent magnet stepper motor is considered for use in high-performance positioning systems. A model-based control law is developed using the exact linearization methodology and implemented on an industrial setup. The practical issues of speed estimation and voltage saturation are considered and resolved through the use of a nonlinear observer and field-weakening, respectively. The results of the implementation of the control algorithm for an industry-specified point-to-point move of a linear positioning table are presented and discussed. >
Usability comparison of three clinical trial management systems

To advise in the selection of a clinical trial management system (CTMS), we evaluated three candidate applications. After preliminary analyses,we performed heuristic evaluation and usability testing to assess system's usability. Velos eResearch,a commercial CTMS, had the best usability outcome despite having fewer features in comparison. In the decision process, the "ease-of-use" aspect was more valued than functionality.
The IRX–β Relation: Insights from Simulations

We study the relationship between the UV continuum slope and infrared excess ( ) predicted by performing dust radiative transfer on a suite of hydrodynamical simulations of galaxies. Our suite includes both isolated disk galaxies and mergers intended to be representative of galaxies at both and . Our low-redshift systems often populate a region around the locally calibrated Meurer et al. relation but move above the relation during merger-induced starbursts. Our high-redshift systems are blue and IR luminous and therefore lie above the Meurer et al. relation. The value of β strongly depends on the dust type used in the RT simulation: Milky-Way-type dust leads to significantly more negative (bluer) slopes compared with Small-Magellanic-Cloud-type dust. The effect on β due to variations in the dust composition with galaxy properties or redshift is the dominant model uncertainty. The dispersion in β is anticorrelated with specific star formation rate (sSFR) and tends to be higher for the simulations. In the actively star-forming simulated galaxies, dust attenuation dominates the dispersion in β, whereas in the simulations, the contributions of star formation history (SFH) variations and dust are similar. For low-sSFR systems at both redshifts, SFH variations dominate the dispersion. Finally, the simulated isolated disks and mergers both occupy a region in the plane consistent with observed dusty star-forming galaxies (DSFGs). Thus, contrary to some claims in the literature, the blue colors of high-z DSFGs do not imply that they are short-lived starbursts.
"Don't forget to take the cupcakes out of the oven": prospective memory, strategic time-monitoring, and context.

Strategies employed by children in tasks requiring prospective memory (i.e., remembering to do something in the future) were investigated to illuminate the nature of the processes involved, and their developmental and contextual determinants. Efficient strategy use was expected to increase with age but to decrease in an unfamiliar setting or on a task associated with higher sex-role expectations. Children were instructed to perform future activities after waiting 30 min. Children's clock-checking during the waiting period was assessed in their own homes or a university psychophysics laboratory. As predicted, strategic time-monitoring occurred less frequently in the laboratory than in the home. The anticipated differences associated with higher sex-role expectations and age were most salient for older boys in the laboratory setting. The findings indicate that, when observed in a familiar setting, children can be shown to employ sophisticated cognitive strategies. Emphasis is placed on the scientific power of the laboratory as a contrasting context for illuminating developmental processes.
Identification of regulatory residues of the yeast adenylyl cyclase.

We have attempted to identify amino acid residues of the yeast adenylyl cyclase that are involved in the regulation of its activity, by isolating adenylyl cyclase‐linked spontaneous mutations capable of suppressing the temperature‐sensitive phenotype of ras1‐ ras2‐ts1 strains. We previously identified a mutated adenylyl cyclase in which a single point mutation, called CR14, led to the replacement of threonine 1651 with isoleucine. We have now investigated the biological effects of CR14, and of other mutations that cause the replacement of threonine 1651 by distinct amino acids. We have observed that the response of adenylyl cyclase to Ras can be either enhanced or attenuated, without significant effects on the steady‐state level of the former enzyme in vivo, depending on the amino acid side chain at position 1651. Therefore, this residue identifies a regulatory region on the adenylyl cyclase molecule. We have also taken advantage of the attenuation of adenylyl cyclase function caused by the replacement of threonine 1651 with aspartic acid to isolate intragenic suppressor mutations. We have identified several point mutations, leading to single amino acid substitutions, individually capable of reactivating the attenuated adenylyl cyclase. The corresponding amino acid changes are located within a relatively small region, including residues 1331, 1345, 1348 and 1374. This region could be physiologically involved in the negative control of the carboxy‐terminal catalytic domain.
Initial viral load determines the magnitude of the human CD8 T cell response to yellow fever vaccination

Significance Current vaccine development against persistent infections such as HIV and tuberculosis focuses on eliciting CD8 T cell immunity through the use of replication-incompetent or single-cycle vectors. Although inherently safe, these vectors deliver limited amounts of antigen. We investigate how antigen load affects the CD8 response by analyzing the viral load and the magnitude of the specific CD8 response after immunization with the live attenuated yellow fever vaccine (YFV-17D). Our results show that the magnitude of the CD8 response is proportional to the amount of antigen when virus load is below a threshold value and saturates above. This finding highlights the requirement that T cell-based vaccines deliver sufficient antigen to elicit a large CD8 response that may be needed for protection. CD8 T cells are a potent tool for eliminating intracellular pathogens and tumor cells. Thus, eliciting robust CD8 T-cell immunity is the basis for many vaccines under development. However, the relationship between antigen load and the magnitude of the CD8 T-cell response is not well-described in a human immune response. Here we address this issue by quantifying viral load and the CD8 T-cell response in a cohort of 80 individuals immunized with the live attenuated yellow fever vaccine (YFV-17D) by sampling peripheral blood at days 0, 1, 2, 3, 5, 7, 9, 11, 14, 30, and 90. When the virus load was below a threshold (peak virus load < 225 genomes per mL, or integrated virus load < 400 genome days per mL), the magnitude of the CD8 T-cell response correlated strongly with the virus load (R2 ∼ 0.63). As the virus load increased above this threshold, the magnitude of the CD8 T-cell responses saturated. Recent advances in CD8 T-cell–based vaccines have focused on replication-incompetent or single-cycle vectors. However, these approaches deliver relatively limited amounts of antigen after immunization. Our results highlight the requirement that T-cell–based vaccines should deliver sufficient antigen during the initial period of the immune response to elicit a large number of CD8 T cells that may be needed for protection.
Using ferritin levels to determine iron-deficiency anemia in pregnancy.

BACKGROUND Standard obstetrical practice has included iron therapy for patients with anemia without requiring the determination of iron deficiency. However, the proportion of pregnant women with anemia who have such a deficiency may be relatively modest. We instituted a practice protocol using serum ferritin levels to determine the proportion of women undergoing prenatal care who had both anemia and iron deficiency. METHODS We evaluated consecutive women entering prenatal care. Those with anemia (hemoglobin level <11 mg/dL) underwent testing for serum ferritin level and other hematologic variables. RESULTS A total of 182 patients entered prenatal care. Hemoglobin data were available for 173 (95%). Thirty-eight (22%) had anemia (hemoglobin level <11 mg/dL); 1 of those women was excluded from the study. Using a ferritin level of 12 mg per dL as the cutoff for iron deficiency, 54% (20) of the 37 remaining patients with anemia had an iron deficiency, and 46% (17) had anemia not related to such a deficiency. Use of hematologic indices provided on complete blood count were not useful in predicting iron deficiency based on serum ferritin levels. CONCLUSIONS In our population of prenatal patients with anemia, only approximately half had an iron deficiency. Diagnostic and therapeutic approaches to screening for anemia in pregnancy should be reconsidered and further evaluated.
Cone visual pigments of the Australian marsupials, the stripe-faced and fat-tailed dunnarts: Sequence and inferred spectral properties

Studies of color vision in marsupial mammals have been very limited. Two photoreceptor genes have been characterized from the tammar wallaby, but a third cone pigment was suggested by microspectrophotometric measurements on cone photoreceptors in two other species, including the fat-tailed dunnart, Sminthopsis crassicaudata. To determine the sequence and infer absorption maxima of the cone photoreceptor pigments of S. crassicaudata and the related stripe-faced dunnart (Sminthopsis macroura), we have used evolutionarily conserved sequences of the cone pigments of other species, including the tammar wallaby, to design primers to amplify the S. macroura and S. crassicaudata pigment sequences by the polymerase chain reaction (PCR) using genomic DNA or retinal cDNA as a template. These primers will be useful for amplifying cone opsin coding sequences from a variety of vertebrates. Amplified products were directly sequenced to determine gene structure and coding sequences. The inferred amino acid sequences of the cone visual pigments indicated that both species have middle-wave-sensitive (MWS) pigments with a predicted absorption maximum (λmax) at 530 nm, and ultraviolet-sensitive (UVS) pigments with a predicted λmax at 360 nm. The MWS pigments of the two species differ by two, and UVS by three amino acid positions. No evidence was obtained for a third cone pigment in either species.
Berufliche Weiterbildung von Arbeitslosengeld-II-Empfängern. Langfristige Wirkungsanalysen

Abstract Wie wirkt berufliche Weiterbildung auf Arbeitslosengeld-IIEmpfanger in einer Langfrist-Perspektive? Mit dem Eintritt in berufliche Weiterbildung beginnt die Investitionsphase mit geringerer Suchintensitat und daraus folgenden geringeren Beschaftigungschancen und einem geringeren Durchschnittslohn als ohne Teilnahme. Nachdem die Weiterbildung abgeschlossen ist, zeigt sich ihre positive Wirkung auf die Beschaftigungschancen, den Lohn und die Vermeidung von weiterem Arbeitslosengeld-II-Bezug. Diese positive Wirkung bleibt langfristig stabil und zeigt auch am Ende des Beobachtungszeitraums keine abnehmende Tendenz (hier uber 8 ½ Jahre nach Beginn). Lange Weiterbildungen ab einem Jahr Dauer entfalten deutlich starkere positive Effekte als berufliche Weiterbildungen mit kurzeren Forderdauern. Long-term Effects of Vocational Training for Unemployment Benefit Recipients in Germany Is vocational training for unemployment benefit recipients effective in a long-term perspective? The beginning of a vocatio.
1H- and 31P-nuclear magnetic resonance studies of l-lactate transport in isolated muscle fibers from the spiny lobster Panulirus argus

Proton (1H) and phosphorus (31P) nuclear magnetic resonance (NMR) spectroscopy were used to investigate the mode of transport of l-lactate across the plasma membranes of the abdominal extensor muscles of the spiny lobster Panulirus argus. Individual fibers or bundles of 2­3 fibers were superfused in a dual-tuned (1H, 31P) microsolenoid NMR probe. 1H-NMR spectra were diffusion-weighted, which eliminated the signal contribution of the fast-flowing extracellular lactate but retained that of intracellular lactate. Well-resolved intracellular lactate signals could be acquired at 15 s intervals, permitting estimation of initial velocities (Vi) of influx and efflux during loading/unloading of muscle fibers. 31P-NMR spectra were acquired to assess cellular energy status and intracellular pH. Transport results showed that Vi values for influx and efflux were a linear function of total lactate concentration, displaying no saturation effects. The rate of lactate influx was enhanced by increasing the concentration of the free acid by altering the superfusate pH. Vi values for influx and efflux of d- and l-lactate were identical. Finally, traditional inhibitors of monocarboxylate and/or anion transport had no effect on influx/efflux of lactate from these cells. The above results strongly suggest that the primary mode of lactate transport is by passive diffusion. These cells appear to lack a monocarboxylate transporter, which may be related to the apparent absence of organ-specific compartmentation of lactate metabolism in crustaceans.
Inflammatory serum markers in patients with multiple trauma. Can they predict outcome?

Clinical trials have provided information concerning the various immunological alterations that occur after trauma which may cause the multiple organ dysfunction syndrome (MODS) and death. Once multiple systems are dysfunctional the rates of mortality are as high as 50%, the morbidity is severe and the costs of health care are enormous. 1,2 Although external support such as ventilators, dialysis machines and inotropic drugs, is provided to all patients to compensate for the internal dysfunction until they can support themselves, the end result is often unpredictable. Early evaluation of the prognosis in polytraumatised patients is difficult. Traditionally, the clinical condition and management of the patient are assessed by evaluation of cardiovascular, renal, liver and respiratory functions. Nevertheless, the significance of such clinical parameters as the urinary output, oxygen saturation, blood gases, C-reactive protein, base excess, etc, is limited since only patients with a clearly impaired organ function can be distinguished. Organ dysfunction which is not detectable by these parameters does not guarantee a condition of the patient which is stable enough for operation especially if in the ‘borderline condition’. 3
BasT, a membrane‐bound transducer protein for amino acid detection in Halobacterium salinarum

Halophilic archaea, such as eubacteria, use methyl‐accepting chemotaxis proteins (MCPs) to sense their environment. We show here that BasT is a halobacterial transducer protein (Htp) responsible for chemotaxis towards five attractant amino acids. The C‐terminus of the protein exhibits the highly conserved regions that are diagnostic for MCPs: the signalling domain for communication with the histidine kinase and the methylation sites that interact with the methylation/demethylation enzymes for adaptation. Hydropathy analysis predicts an enterobacterial‐type transducer protein topology for BasT, with an extracellular putative ligand‐binding domain flanked by two transmembrane helices and a cytoplasmic domain. BasT‐inactivated mutant cells are missing a membrane protein radiolabelled with l‐[methyl‐3H]‐methionine in wild‐type cells, confirming that BasT is methylatable and membrane bound. Behavioural analysis of the basT mutant cells by capillary and chemical‐in‐plug assays demonstrates complete loss of chemotactic responses towards five (leucine, isoleucine, valine, methionine and cysteine) of the six attractant amino acids for Halobacterium salinarum, whereas they still respond to arginine. The volatile methyl group production assays also corroborate these findings and confirm that BasT signalling induces methyl group turnover. Our data identify BasT as the chemotaxis transducer protein for the branched chain amino acids leucine, isoleucine and valine as well as for methionine and cysteine. Thus, BasT and the arginine sensor Car cover the entire spectrum of chemotactic responses towards attractant amino acids in H. salinarum.
Required Roles of Bax and JNKs in Central and Peripheral Nervous System Death of Retinoblastoma-deficient Mice*

Retinoblastoma-deficient mice show massive neuronal damage and deficits in both CNS and PNS tissue. Previous work in the field has shown that death is regulated through distinct processes where CNS tissue undergoes death regulated by the tumor suppressor p53 and the apoptosome component, APAF1. Death in the PNS, however, is independent of p53 and reliant on the death protease, caspase 3. In the present study, we more carefully delineated the common and distinct mechanisms of death regulation by examining the stress-activated kinases, JNK2 and 3, the conserved Bcl-2 member Bax, and the relationship among these elements including p53. By use of genetic modeling, we show that death in various regions of the CNS and DRGs of the PNS is reliant on Bax. In the CNS, Bax acts downstream of p53. The relevance of the JNKs is more complex, however. Surprisingly, JNK3 deficiency by itself does not inhibit c-Jun phosphorylation and instead, aggravates death in both CNS and PNS tissue. However, JNK2/3 double deficiency blocks death due to Rb loss in both the PNS and CNS. Importantly, the relationships between JNKs, p53, and Bax exhibit regional differences. In the medulla region of the hindbrain in the CNS, JNK2/3 deficiency blocks p53 activation. Moreover, Bax deficiency does not affect c-Jun phosphorylation. This indicates that a JNK-p53-Bax pathway is central in the hindbrain. However, in the diencephalon regions of the forebrain (thalamus), Bax deficiency blocks c-Jun activation, indicating that a Bax-JNK pathway of death is more relevant. In the DRGs of the PNS, a third pathway is present. In this case, a JNK-Bax pathway, independent of p53, regulates damage. Accordingly, our results show that a death regulator Bax is common to death in both PNS and CNS tissue. However, it is regulated by or itself regulates different effectors including the JNKs and p53 depending upon the specific region of the nervous system.