Miracle-dz/UniFAR-FTUs huggingface dataset:
Release and sequestration of calcium by ryanodine‐sensitive stores in rat hippocampal neurones

1 The properties of ryanodine‐sensitive Ca2+ stores in CA1 pyramidal cells were investigated in rat hippocampal slices by using whole‐cell patch‐clamp recordings combined with fura‐2‐based fluorometric digital imaging of cytoplasmic Ca2+ concentration ([Ca2+]i). 2 Brief pressure applications of caffeine onto the somata of pyramidal cells caused large transient increases in [Ca2+]i (Ca2+ transients) of 50–600 nm above baseline. 3 The Ca2+ transients evoked by caffeine at −60 mV were not associated with an inward current, persisted after blocking voltage‐activated Ca2+ currents and were completely blocked by bath‐applied ryanodine. Similar transients were also evoked at +60 mV. Thus, these transients reflect Ca2+ release from intracellular ryanodine‐sensitive Ca2+ stores. 4 The Ca2+ transients evoked by closely spaced caffeine pulses rapidly decreased in amplitude, indicating progressive depletion of the Ca2+ stores. The amplitude of the Ca2+ transients recovered spontaneously with an exponential time constant of 59 s. Recovery was accelerated by depolarization‐induced elevations in [Ca2+]i and blocked by cyclopiazonic acid (CPA) and thapsigargin, indicating that store refilling is mediated by endoplasmic reticulum Ca2+‐ATPases. 5 Even without prior store depletion the caffeine‐induced Ca2+ transients disappeared after 6 min exposure to CPA, suggesting that ryanodine‐sensitive Ca2+ stores are maintained at rest by continuous Ca2+ sequestration. 6 Caffeine‐depleted Ca2+ stores did not refill in Ca2+‐free saline, suggesting that the refilling of the stores depends upon Ca2+ influx through a ‘capacitative‐like’ transmembrane influx pathway operating at resting membrane potential. The refilling of the stores was also blocked by Ni2+ and gallopamil (D600). 7 Elevations of basal [Ca2+]i produced by bath‐applied KCl markedly potentiated (up to 6‐fold) the caffeine‐induced Ca2+ transients. The degree of potentiation was positively related to the increase in basal [Ca2+]i. The Ca2+ transients remained potentiated up to 9 min after reversing the KCl‐induced [Ca2+]i increase. Thus, the ryanodine‐sensitive Ca2+ stores can ‘overcharge’ when challenged with an increase in [Ca2+]i and slowly discharge excess Ca2+ after basal [Ca2+]i returns to its resting level. 8 Pressure applications of caffeine onto pyramidal cell dendrites evoked local Ca2+ transients similar to those separately evoked in the respective somata. Thus, dendritic ryanodine‐sensitive Ca2+ stores are also loaded at rest and can function as independent compartments. 9 In conclusion, the ryanodine‐sensitive Ca2+ stores in hippocampal pyramidal neurones contain a releasable pool of Ca2+ that is maintained by a Ca2+ entry pathway active at subthreshold membrane potentials. Ca2+ entry through voltage‐gated Ca2+ channels transiently overcharges the stores. Thus, by acting as powerful buffers at rest and as regulated sources during activity, Ca2+ stores may control the waveform of physiological Ca2+ signals in CA1 hippocampal pyramidal neurones.
Structure and accessibility of HA trimers on intact 2009 H1N1 pandemic influenza virus to stem region-specific neutralizing antibodies

Rapid antigenic variation of HA, the major virion surface protein of influenza A virus, remains the principal challenge to the development of broader and more effective vaccines. Some regions of HA, such as the stem region proximal to the viral membrane, are nevertheless highly conserved across strains and among most subtypes. A fundamental question in vaccine design is the extent to which HA stem regions on the surface of the virus are accessible to broadly neutralizing antibodies. Here we report 3D structures derived from cryoelectron tomography of HA on intact 2009 H1N1 pandemic virions in the presence and absence of the antibody C179, which neutralizes viruses expressing a broad range of HA subtypes, including H1, H2, H5, H6, and H9. By fitting previously derived crystallographic structures of trimeric HA into the density maps, we deduced the locations of the molecular surfaces of HA involved in interaction with C179. Using computational methods to distinguish individual unliganded HA trimers from those that have bound C179 antibody, we demonstrate that ∼75% of HA trimers on the surface of the virus have C179 bound to the stem domain. Thus, despite their close packing on the viral membrane, the majority of HA trimers on intact virions are available to bind anti-stem antibodies that target conserved HA epitopes, establishing the feasibility of universal influenza vaccines that elicit such antibodies.
Evaluation of 2 Immunoassays for Monitoring Low Blood Levels of Tacrolimus

The objective of this study was to evaluate the analytical performance of 2 new tacrolimus immunoassays (Dade Dimension Xpand and Abbott ARCHITECT) for therapeutic drug monitoring as possible replacements for the current method in our laboratory, the Abbott IMx tacrolimus assay. Attending physicians at our institute desire to minimize calcineurin inhibitor therapy in kidney allograft recipients to prolong graft survival and improve the quality of life of their patients. Proposed future target trough levels of tacrolimus in whole blood are in the range of 2-4 ng/mL, which requires an assay with a limit of quantification (LOQ) below this range, ideally around 1 ng/mL (European Consensus Recommendation from the Committee on Tacrolimus Optimization). Method comparison analysis of the Dade and ARCHITECT assays showed good correlation to the IMx assay, with correlation coefficients of 0.94 and 0.96, respectively. Both assays reported tacrolimus concentrations lower on average than IMx as demonstrated by slopes of 0.83 (Dade) and 0.93 (ARCHITECT). LOQ for both Dade instruments tested was >4 ng/mL, whereas the LOQ for the ARCHITECT i2000 and i1000 instruments was 0.8 and 0.5 ng/mL, respectively (upper 95% confidence limit). Values reported from both Dade instruments were observed to shift over time, whereas the values on the IMx and ARCHITECT instruments were stable. The Abbott ARCHITECT Tacrolimus assay is a sensitive and precise assay that meets the new LOQ recommendation, 1 ng/mL, for monitoring tacrolimus in whole blood.
Submultiplicative Glivenko-Cantelli and Uniform Convergence of Revenues

In this work we derive a variant of the classic Glivenko-Cantelli Theorem, which asserts uniform convergence of the empirical Cumulative Distribution Function (CDF) to the CDF of the underlying distribution. Our variant allows for tighter convergence bounds for extreme values of the CDF. We apply our bound in the context of revenue learning, which is a well-studied problem in economics and algorithmic game theory. We derive sample-complexity bounds on the uniform convergence rate of the empirical revenues to the true revenues, assuming a bound on the $k$th moment of the valuations, for any (possibly fractional) $k>1$. For uniform convergence in the limit, we give a complete characterization and a zero-one law: if the first moment of the valuations is finite, then uniform convergence almost surely occurs; conversely, if the first moment is infinite, then uniform convergence almost never occurs.
Differences in the gyral pattern distinguish chromosome 17–linked and X-linked lissencephaly

Background: Classical lissencephaly or “smooth brain” is a human brain malformation that consists of diffuse agyria and pachygyria. Two genes associated with classical lissencephaly have recently been cloned—LIS1 from chromosome 17p13.3 and XLIS (also called DCX) from Xq22.3-q23. Objective: We performed genotype-phenotype analysis in children with lissencephaly associated with mutations of different genes. Methods: We compared the phenotype, especially brain imaging studies, in a series of 48 children with lissencephaly, including 12 with Miller-Dieker syndrome (MDS), which is associated with large deletions of LIS1 and other genes in the region, 24 with isolated lissencephaly sequence caused by smaller LIS1 deletions or mutations, and 12 with isolated lissencephaly sequence caused by XLIS mutations. Results: We found consistent differences in the gyral patterns, with the malformation more severe posteriorly in individuals with LIS1 mutations and more severe anteriorly in individuals with XLIS mutations. Thus, mutations of LIS1 are associated with a posterior-to-anterior gradient of lissencephaly, whereas mutations of XLIS are associated with an anterior-to-posterior gradient. We also confirmed differences in severity between MDS and ILS17. Hypoplasia of the cerebellar vermis proved to be more common with XLIS mutations. Conclusion: It is often possible to predict the gene mutation from careful review of brain imaging studies.
Hepatitis C virus genotypes in patients with chronic liver disease and haemodialysis patients from Saudi Arabia

Summary. The genotypes of hepatitis C virus (HCV) were investigated in 28 Saudi patients (21 males, seven females; age range 23–68 years; mean 45.0 years) with histologically proven chronic hepatitis (13 chronic active hepatitis and 15 liver cirrhosis) and in 32 Saudi patients with chronic renal failure maintained on haemodialysis (22 males, 10 females; age range 18–60 years; mean 40.0 years) who also had liver disease due to HCV. Among the 28 patients with chronic liver disease genotype 4 was the predominant one (60.7%), followed by types 1b (21.4%), 1a (14.3%) and 2a (3.6%). The distribution of genotypes was similar in patients with chronic active hepatitis to those with liver cirrhosis. Among the 32 patients with chronic renal failure and maintained on haemodialysis, genotype 4 was also the dominant type (55.0%), followed by 1a (25.0%), 1b (21.9%) and 2a (3.1%). In all categories studied the prevalence of genotypes between males and females was the same. As our patients were selected from various regions of Saudi Arabia, we believe that genotype 4 is the predominant one throughout the whole kingdom.
Acute Improvement of Vertical Jump Performance After Isometric Squats Depends on Knee Angle and Vertical Jumping Ability

Abstract Tsoukos, A, Bogdanis, GC, Terzis, G, and Veligekas, P. Acute improvement of vertical jump performance after isometric squats depends on knee angle and vertical jumping ability. J Strength Cond Res 30(8): 2250–2257, 2016—This study examined the acute effects of maximum isometric squats at 2 different knee angles (90 or 140°) on countermovement jump (CMJ) performance in power athletes. Fourteen national-level male track and field power athletes completed 3 main trials (2 experimental and 1 control) in a randomized and counterbalanced order 1 week apart. Countermovement jump performance was evaluated using a force-plate before and 15 seconds, 3, 6, 9, and 12 minutes after 3 sets of 3 seconds maximum isometric contractions with 1-minute rest in between, from a squat position with knee angle set at 90 or 140°. Countermovement jump performance was improved compared with baseline only in the 140° condition by 3.8 ± 1.2% on the 12th minute of recovery (p = 0.027), whereas there was no change in CMJ height in the 90° condition. In the control condition, there was a decrease in CMJ performance over time, reaching −3.6 ± 1.2% (p = 0.049) after 12 minutes of recovery. To determine the possible effects of baseline jump performance on subsequent CMJ performance, subjects were divided into 2 groups (“high jumpers” and “low jumpers”). The baseline CMJ values of “high jumpers” and “low jumpers” differed significantly (CMJ: 45.1 ± 2.2 vs. 37.1 ± 3.9 cm, respectively, p = 0.001). Countermovement jump was increased only in the “high jumpers” group by 5.4 ± 1.4% (p = 0.001) and 7.4 ± 1.2% (p = 0.001) at the knee angles of 90 and 140°, respectively. This improvement was larger at the 140° angle (p = 0.049). Knee angle during isometric squats and vertical jumping ability are important determinants of the acute CMJ performance increase observed after a conditioning activity.
Nonlinear robust control to maximize energy capture in a variable speed wind turbine using an induction generator

The emergence of wind turbine systems for electric power generation can help satisfy the growing global demand. This paper proposes a control strategy to maximize the wind energy captured in a variable speed wind turbine, with an internal induction generator, at low to medium wind speeds. The proposed strategy controls the tip speed ratio, via the rotor angular speed, to an optimum point at which the efficiency constant (or power coefficient) is maximal for a particular blade pitch angle and wind speed. This control method allows for aerodynamic rotor power maximization without exact wind turbine model knowledge.
To Draw or Not to Draw? Examining the Necessity of Problem Diagrams Using Massive Open Online Course Experiments.

Zhongzhou Chen, Neset Demirci, Youn-Jeng Choi, and David E. Pritchard Department of Physics, University of Central Florida, Orlando, Florida 32816, USA Department of Educational Studies in Psychology, Research Methodology & Counseling, University of Alabama, Tuscaloosa, Alabama 35487, USA Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA (Received 5 April 2016; published 17 February 2017)
Ensemble of CNNs for Steganalysis: An Empirical Study

There has been growing interest in using convolutional neural networks (CNNs) in the fields of image forensics and steganalysis, and some promising results have been reported recently. These works mainly focus on the architectural design of CNNs, usually, a single CNN model is trained and then tested in experiments. It is known that, neural networks, including CNNs, are suitable to form ensembles. From this perspective, in this paper, we employ CNNs as base learners and test several different ensemble strategies. In our study, at first, a recently proposed CNN architecture is adopted to build a group of CNNs, each of them is trained on a random subsample of the training dataset. The output probabilities, or some intermediate feature representations, of each CNN, are then extracted from the original data and pooled together to form new features ready for the second level of classification. To make best use of the trained CNN models, we manage to partially recover the lost information due to spatial subsampling in the pooling layers when forming feature vectors. Performance of the ensemble methods are evaluated on BOSSbase by detecting S-UNIWARD at 0.4 bpp embedding rate. Results have indicated that both the recovery of the lost information, and learning from intermediate representation in CNNs instead of output probabilities, have led to performance improvement.
Effect of Rough Surfaces Upon Gingival Tissue

IT IS generally agreed that unpolished restorations situated below the gingival margin will cause a more severe irritation than well-polished ones. Experimental histologic investigations2 have shown that the epithelium under favorable conditions can join the surface of acrylic crowns in the same way as a normal epithelial cuff' (epithelial attachment) joins the tooth. Signs of irritation were found mainly next to the junction between the tooth and the artificial crown, or in places where large remnants of cement had been left in contact with the soft tissue. From this the conclusion was drawn that zincoxyphosphate cement acts as an irritant upon the gingiva while a polished acrylic surface does not. It also has been generally accepted that subgingival calculus acts as an irritant upon the gingival tissue on account of its roughness. Experimental bacteriologic investigations have shown that pockets with subgingival calculus always contain bacteria, while pockets without subgingival calculus usually are sterile. Even pockets around well-fitting artificial crowns can, under favorable conditions, be sterile. From this the conclusion was drawn that the bacteria are the main source of irritation in calculus. Where cement is concerned it is impossible to decide whether the irritation is caused by chemical agents in the cement itself or by its rough surface injuring the epithelium mechanically. Where calculus is concerned it is in the same way impossible to determine whether the irritation is caused by the bacteria alone, or whether the uneven surface of the calculus to a certain degree plays a role. The following work was carried out to determine whether or not a decidedly rough surface below the gingival margin will prevent healing and act as a permanent irritant.
CCL19 and CCL28 Augment Mucosal and Systemic Immune Responses to HIV-1 gp140 by Mobilizing Responsive Immunocytes into Secondary Lymph Nodes and Mucosal Tissue

Induction of broad and potent neutralizing Abs at the mucosal portals of entry remains a primary goal for most vaccines against mucosally acquired viral infections. Selection of appropriate adjuvants capable of promoting both systemic and mucosal responses will be crucial for the development of effective immunization strategies. In this study, we investigated whether plasmid codelivery of cytokines APRIL, CCL19, or CCL28 can enhance Ag-induced immune responses to HIV-1 gp140. Our results demonstrated that pCCL19 and pCCL28, but not pAPRIL, significantly enhanced Ag-specific systemic and mucosal Ab responses. gp140-specific Abs in serum enhanced by pCCL19 or pCCL28 were broadly distributed across all four IgG subclasses, of which IgG1 was predominant. The enhanced systemic and mucosal Abs showed increased neutralizing activity against both homologous and heterologous HIV-1, and potency correlated with gp140-specific serum IgG and vaginal IgA levels. Measurement of gp140-specific cytokines produced by splenocytes demonstrated that pCCL19 and pCCL28 augmented balanced Th1/Th2 responses. pCCL19 and pCCL28 also increased IgA+ cells in colorectal mucosal tissue. pCCL19 codelivery resulted in an increase of CCR7+ CD11c+ cells in mesenteric lymph nodes and both CCR7+ CD11c+ cells and CCR7+ CD3e+ cells in spleen, whereas pCCL28 codelivery resulted in an augment of CCR10+ CD19+ cells in both spleen and mesenteric lymph nodes. Together, our data indicate that pCCL19 and pCCL28 can enhance HIV-1 envelope–specific systemic and mucosal Ab responses, as well as T cell responses. Such enhancements appear to be associated with mobilization of responsive immunocytes into secondary lymphoid organs and mucosal tissues through interactions with corresponding receptors.
Determination of Supersymmetric Particle Masses and Attributes with Genetic Divisors

Arithmetic conditions relating particle masses can be defined on the basis of (1) the supersymmetric conservation of congruence and (2) the observed characteristics of particle reactions and stabilities. Stated in the form of common divisors, these relations can be interpreted as expressions of genetic elements that represent specific particle characteristics. In order to illustrate this concept, it is shown that the pion triplet ({pi}{sup {+-}}, {pi}{sup 0}) can be associated with the existence of a greatest common divisor d{sub 0{+-}} in a way that can account for both the highly similar physical properties of these particles and the observed {pi}{sup {+-}}/{pi}{sup 0} mass splitting. These results support the conclusion that a corresponding statement holds generally for all particle multiplets. Classification of the respective physical states is achieved by assignment of the common divisors to residue classes in a finite field F{sub P{sub {alpha}}} and the existence of the multiplicative group of units F{sub P{sub {alpha}}} enables the corresponding mass parameters to be associated with a rich subgroup structure. The existence of inverse states in F{sub P{sub {alpha}}} allows relationships connecting particle mass values to be conveniently expressed in a form in which the genetic divisor structure is prominent. An examplemore » is given in which the masses of two neutral mesons (K{degree} {r_arrow} {pi}{degree}) are related to the properties of the electron (e), a charged lepton. Physically, since this relationship reflects the cascade decay K{degree} {r_arrow} {pi}{degree} + {pi}{degree}/{pi}{degree} {r_arrow} e{sup +} + e{sup {minus}}, in which a neutral kaon is converted into four charged leptons, it enables the genetic divisor concept, through the intrinsic algebraic structure of the field, to provide a theoretical basis for the conservation of both electric charge and lepton number. It is further shown that the fundamental source of supersymmetry can be expressed in terms of hierarchical relationships between odd and even order subgroups of F{sub P{sub {alpha}}}, an outcome that automatically reflects itself in the phenomenon of fermion/boson pairing of individual particle systems. Accordingly, supersymmetry is best represented as a group rather than a particle property. The status of the Higgs subgroup of order 4 is singular; it is isolated from the hierarchical pattern and communicates globally to the mass scale through the seesaw congruence by (1) fusing the concepts of mass and space and (2) specifying the generators of the physical masses. « less
Insulin-Like Growth Factor (IGF) Signaling through Type 1 IGF Receptor Plays an Important Role in Remyelination

We examined the role of IGF signaling in the remyelination process by disrupting the gene encoding the type 1 IGF receptor (IGF1R) specifically in the mouse brain by Cre-mediated recombination and then exposing these mutants and normal siblings to cuprizone. This neurotoxicant induces a demyelinating lesion in the corpus callosum that is reversible on termination of the insult. Acute demyelination and oligodendrocyte depletion were the same in mutants and controls, but the mutants did not remyelinate adequately. We observed that oligodendrocyte progenitors did not accumulate, proliferate, or survive within the mutant mice, compared with wild type, indicating that signaling through the IGF1R plays a critical role in remyelination via effects on oligodendrocyte progenitors.