Miracle-dz/UniFAR-FTUs huggingface dataset:
Myelin basic protein specific T cell lines and clones derived from the CNS of rats with EAE only recognize encephalitogenic epitopes

The epitope specificities of myelin basic protein (BP) specific T cell lines derived from the spinal cords (SC) and lymph nodes (LN) of rats with experimental autoimmune encephalomyelitis (EAE) were compared. To induce EAE, Lewis rats were immunized with guinea pig (GP)‐BP and complete Freund's adjuvant. Mononuclear cells from the SC and LN of these animals proliferated in response to BP and the purified protein derivative (PPD) of mycobacterium. After initially being cultured in growth medium, SC mononuclear cells had an enhanced response to BP and lost their response to PPD. LN cells cultured in identical conditions lost their response to both BP and PPD. LN‐derived BP specific cell lines recognized only two epitopes of GP‐BP: an encephalitogenic epitope in residues 72–89 and a non‐encephalitogenic epitope in residues 43–68. SC‐derived BP specific cell lines and clones recognized the 72–89 epitope and a second encephalitogenic epitope contained in residues 87–99 but not the non‐encephalitogenic 43–68 epitope. Unlike those from LN, BP‐specific T cell lines and clones derived from the CNS appear to recognize only encephalitogenic epitopes, including epitopes not recognized by LN lines.
The anomalous behavior of the density of water in the range 30 K < T < 373 K

The temperature dependence of the density of water, ρ(T), is obtained by means of optical scattering data, Raman and Fourier transform infrared, in a very wide temperature range, 30 < T < 373 K. This interval covers three regions: the thermodynamically stable liquid phase, the metastable supercooled phase, and the low-density amorphous solid phase, at very low T. From analyses of the profile of the OH stretching spectra, we determine the fractional weight of the two main spectral components characterized by two different local hydrogen bond structures. They are, as predicted by the liquid–liquid phase transition hypothesis of liquid water, the low- and the high-density liquid phases. We evaluate contributions to the density of these two phases and thus are able to calculate the absolute density of water as a function of T. We observe in ρ(T) a complex thermal behavior characterized not only by the well known maximum in the stable liquid phase at T = 277 K, but also by a well defined minimum in the deeply supercooled region at 203 ± 5 K, in agreement with suggestions from molecular dynamics simulations.
Whole blood thrombin generation in Bmal1-deficient mice

Summary The Calibrated Automated Thrombogram (CAT) assay that measures thrombin generation (TG) in platelet-poor and -rich plasma, is increasingly being recognised as a more sensitive tool to determine the overall function of the haemostatic system. We developed a method enabling the measurement of TG in a small aliquot of blood. The objective was to validate this assay in mouse blood and to examine the rate and extent of TG in a mouse model of premature aging. TG was assayed in blood from 20– to 28-week-old brain and muscle ARNT-like protein-1 (Bmal1)-deficient (knockout, KO) mice and wild-type (WT) littermates. Bmal1-KO mice are known to display symptoms of premature aging. TG was initiated by adding calcium, tissue factor and a thrombin specific substrate. After TG, the samples were prepared for scanning electron microscopy (SEM). The intra-assay variations (%) in mouse blood of the endogenous thrombin potential (ETP), peak height, lag time, time-to-peak and velocity index were 10% or less (n=24). We found that Bmal1-KO mice have a significantly (p<0.001) higher ETP (437 ± 7 nM.min; mean ± SD, n=7) when compared with WT mice (ETP=220 ± 45 nM.min; mean ± SD, n=5). The peak heights also differed significantly (p=0.027). By applying SEM we found that Bmal1 deficient mice display a denser fibrin network with smaller pores compared to WT mice. In conclusion, the whole blood TG assay in mice revealed to be reproducible. As a proof-of-principle we have shown that the whole blood TG assay is capable of detecting a prothrombotic phenotype in Bmal1-KO mice.
Tween‐80 and impurity induce anaphylactoid reaction in zebrafish

A number of recent reports suspected that Tween‐80 in injectable medicines, including traditional Chinese medicine injections could cause life‐threatening anaphylactoid reaction, but no sound conclusion was drawn. A drug‐induced anaphylactoid reaction is hard to be assayed in vitro and in conventional animal models. In this study, we developed a microplate‐based quantitative in vivo zebrafish assay for assessing anaphylactoid reaction and live whole zebrafish mast cell tryptase activity was quantitatively measured at a wavelength of 405 nm using N‐benzoyl‐dl‐arginine p‐nitroanilide as a substrate. We assessed 10 batches of Tween‐80 solutions from various national and international suppliers and three Tween‐80 impurities (ethylene glycol, 2‐chloroethanol and hydrogen peroxide) in this model and found that three batches of Tween‐80 (nos 2, 20080709 and 20080616) and one Tween‐80 impurity, hydrogen peroxide (H2O2), induced anaphylactoid reactions in zebrafish. Furthermore, we found that H2O2 residue and peroxide value were much higher in Tween‐80 samples 2, 20080709 and 20080616. These findings suggest that H2O2 residue in combination with oxidized fatty acid residues (measured as peroxide value) or more likely the oxidized fatty acid residues in Tween‐80 samples, but not Tween‐80 itself, may induce anaphylactoid reaction. High‐throughput zebrafish tryptase assay developed in this report could be used for assessing safety of Tween‐80‐containing injectable medicines and potentially for screening novel mast cell‐modulating drugs. Copyright © 2014 John Wiley & Sons, Ltd.
Sleep in Major Depression: Relation to Memory Performance and Outcome after Interpersonal Psychotherapy

Background: Earlier findings suggest both a link between sleep and memory consolidation and a relationship between abnormal sleep at baseline and poor treatment outcome in major depression after interpersonal psychotherapy (IPT). Methods: Pre-treatment polysomnography was examined in 32 patients with a major depressive episode (mean age = 39.5 years, 20 women). Declarative memory was tested by the Rey-Osterrieth Complex Figure Test and a paired associative word list and procedural learning was assessed by a mirror tracing skill. All patients were treated with IPT according to the manual and did not receive any antidepressant medication. Twenty-three patients took part in a minimum of 12 sessions of IPT. Remission was defined as 2 consecutive weeks with a score <8 on the Hamilton Rating Scale of Depression. Results: Declarative visual memory performance was associated with total sleep time and total amount of rapid eye movement sleep. In IPT remitters (n = 14), there was a trend towards a decrease in rapid eye movement density (first period) and a significant decrease in delta power in pre-treatment sleep in comparison to non-remitters (n = 9). Treatment outcome after IPT was also associated with declarative memory performance at baseline (as a trend). Conclusions: Further indications of a role of sleep in memory processes and of the importance of specific sleep parameters as markers for a positive treatment response to psychotherapy were found.
PTEN hamartoma tumor syndrome: An overview

PTEN hamartoma tumor syndrome (PHTS) encompasses four major clinically distinct syndromes associated with germline mutations in the tumor suppressor PTEN. These allelic disorders, Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, and Proteus-like syndrome are associated with unregulated cellular proliferation leading to the formation of hamartomas. Thus far, an increased risk of malignancy has only been documented in Cowden syndrome; however, current recommendations advise that all individuals with PTEN hamartoma tumor syndrome follow the cancer surveillance strategies suggested for Cowden syndrome until further data indicate otherwise. Because any individual phenotypic feature of Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome are frequently present in the general population, many individuals often go undiagnosed and consequently do not benefit from available cancer surveillance strategies. Therefore, it is critical for clinicians to recognize the phenotypic features associated with these syndromes to accurately diagnose and provide preventative care. This overview details the clinical description of the PTEN hamartoma tumor syndrome and associated disorders, their diagnosis and molecular/genetic testing, as well as differential diagnosis for assessment of other hamartoma-associated syndromes.
TT-301 Inhibits Microglial Activation and Improves Outcome after Central Nervous System Injury in Adult Mice

Background: Microglial inhibition may reduce secondary tissue injury and improve functional outcome following acute brain injury. Utilizing clinically relevant murine models of traumatic brain injury and intracerebral hemorrhage, neuroinflammatory responses and functional outcome were examined in the presence of a potential microglial inhibitor, TT-301. Methods: TT-301 or saline was administered following traumatic brain injury or intracerebral hemorrhage, and then for four subsequent days. The effect of TT-301 on neuroinflammatory responses and neuronal viability was assessed, as well as short-term vestibulomotor deficit (Rotorod) and long-term neurocognitive impairment (Morris water maze). Finally differential gene expression profiles of mice treated with TT-301 were compared with those of vehicle. Results: Reduction in F4/80+ staining was demonstrated at 1 and 10 days, but not 28 days, after injury in mice treated with TT-301 (n = 6). These histologic findings were associated with improved neurologic function as assessed by Rotorod, which improved by 52.7% in the treated group by day 7, and Morris water maze latencies, which improved by 232.5% as a function of treatment (n = 12; P < 0.05). Similar benefit was demonstrated following intracerebral hemorrhage, in which treatment with TT-301 was associated with functional neurologic improvement of 39.6% improvement in Rotorod and a reduction in cerebral edema that was independent of hematoma volume (n = 12; P < 0.05). Differential gene expression was evaluated following treatment with TT-301, and hierarchical cluster analysis implicated involvement of the Janus kinase–Signal Transducer and Activator of Transcription pathway after administration of TT-301 (n = 3/group). Conclusions: Modulation of neuroinflammatory responses through TT-301 administration improved histologic and functional parameters in murine models of acute neurologic injury.
Evidence of a hybrid‐zone in Atlantic cod (Gadus morhua) in the Baltic and the Danish Belt Sea revealed by individual admixture analysis

The study of hybrid zones is central to our understanding of the genetic basis of reproductive isolation and speciation, yet very little is known about the extent and significance of hybrid zones in marine fishes. We examined the population structure of cod in the transition area between the North Sea and the Baltic Sea employing nine microsatellite loci. Genetic differentiation between the North Sea sample and the rest increased along a transect to the Baltic proper, with a large increase in level of differentiation occurring in the Western Baltic area. Our objective was to determine whether this pattern was caused purely by varying degrees of mechanical mixing of North Sea and Baltic Sea cod or by interbreeding and formation of a hybrid swarm. Simulation studies revealed that traditional Hardy–Weinberg analysis did not have sufficient power for detection of a Wahlund effect. However, using a model‐based clustering method for individual admixture analysis, we were able to demonstrate the existence of intermediate genotypes in all samples from the transition area. Accordingly, our data were explained best by a model of a hybrid swarm flanked by pure nonadmixed populations in the North Sea and the Baltic Sea proper. Significant correlation of gene identities across loci (gametic phase disequilibrium) was found only in a sample from the Western Baltic, suggesting this area as the centre of the apparent hybrid zone. A hybrid zone for cod in the ecotone between the high‐saline North Sea and the low‐saline Baltic Sea is discussed in relation to its possible origin and maintenance, and in relation to a classical study of haemoglobin variation in cod from the Baltic Sea/Danish Belt Sea, suggesting mixing of two divergent populations without interbreeding.
Aliskiren alleviates doxorubicin-induced nephrotoxicity by inhibiting oxidative stress and podocyte injury

Introduction: Doxorubicin (DXR) is one of the most effective and widely used anthracycline antibiotics. However, its clinical application is hampered by toxic effects in many organs. Nephrotoxicity is one of the major side effects of anthracycline antibiotics. This study was designed to investigate the possible protective effects of aliskiren (a direct renin inhibitor) in DXR-induced nephrotoxicity in rats. Materials and methods: Wistar albino rats were intraperitoneally (ip) injected with DXR and renin activity, albumin, total protein, urea, creatinine levels in plasma and ultrastructural changes in podocytes were assessed. Results: Rats subjected to DXR administration had significant (p<0.01) increases in systolic blood pressure, plasma renin activity, plasma concentration of urea, creatinine and tissue malondialdehyde and significant (p<0.01) reductions in plasma concentrations of albumin, total protein and antioxidant defense (reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT)) in renal tissues. Furthermore, DXR-induced nephrotoxicity has also been characterized by broadening of podocyte foot processes, enlargement of glomerular basement membrane width and reduction in slit pore diameter. The above effects of DXR were significantly (p<0.01) prevented by aliskiren treatment. Conclusions: These findings revealed that the blockade of renin activity by aliskiren is a promising approach in the treatment of DXR-induced nephrotoxicity.
How do Scratch Programmers Name Variables and Procedures?

Research shows the importance of selecting good names to identifiers in software code: more meaningful names improve readability. In particular, several guidelines encourage long and descriptive variable names. A recent study analyzed the use of variable names in five programming languages, focusing on single-letter variable names, because of the apparent contradiction between their frequent use and the fact that these variables violate the aforementioned guidelines. ,,In this paper, we analyze variables in Scratch, a popular block-based language aimed at children. We start by replicating the above single-letter study for Scratch. We augment this study by analyzing single-letter procedure names, and by investigating the use of Scratch specific naming patterns: spaces in variable names, numerics as variables and textual labels in procedure names. ,,The results of our analysis show that Scratch programmers often prefer longer identifier names than developers in other languages, while Scratch procedure names have even longer names than Scratch variables. For the single-letter variables, the most frequent names are x, y, and i. Single-letter procedures are less popular, but show more tendency to be in upper case. When compared to the other programming languages, the usage of single uppercase letters in Scratch variables seems to be similar to the pattern found in Perl, while for the lowercase letters—to the pattern found in Java. Concerning Scratch specific features, 44% of the unique variable names and 34% of the projects in the dataset include at least one space. The usage of textual labels between parameters in procedure names appears as not common, however textual patterns used imply an influence from textual languages, for example by using brackets. ,,Previous research indicate the identifier names as one significant issue in transitioning from visual block-based to textual programming languages. The naming patterns we found support this claim for Scratch programmers who may incur difficulties when transitioning to the use of mainstream textual programming languages. Those languages restrict the use of spaces in identifiers and more often divert into short and single-letter names—tendencies opposite to the naming preferences in Scratch.
A Metabolic Mapping Study of Orientation Discrimination and Detection Tasks in the Cat

Increasing evidence suggests that a large number of distinct cortical areas and associated subcortical structures participate in the processing of visual information and that different aspects of visual scenes are evaluated in different areas. This necessitates identification of cortical and subcortical regions cooperating in particular visual tasks. Using the 2‐deoxyglucose technique, we monitored the differential activation of areas in the cat visual cortex participating in an orientation discrimination and a detection task. Concordant with previous lesion studies, we found increased activity levels in area 17 in the discrimination condition relative to the detection condition. In addition, the 2‐deoxyglucose technique revealed discrimination‐related increased activations in the claustrum, the putamen and in parts of the anteromedial, anterolateral and posterolateral lateral suprasylvian visual areas. Regions activated differentially with the detection task comprised subdivisions of areas 17, 18, 19 and 21, posterior area 7 (7p), several areas of the posterior part of the middle and posterior suprasylvian sulcus, the pulvinar complex and the superior colliculus. These results show that the 2‐deoxyglucose technique is useful to investigate cognitive brain functions, and that different sets of cortical and subcortical regions are activated during two visual tasks with similar visual stimulation.
A CMOS Digital SiPM With Focal-Plane Light-Spot Statistics for DOI Computation

Silicon photomultipliers can be used to infer the depth-of-interaction (DOI) in scintillator crystals. DOI can help to improve the quality of the positron emission tomography images affected by the parallax error. This paper contemplates the computation of DOI based on the standard deviation of the light distribution. The simulations have been carried out by GAMOS. The design of the proposed digital silicon photo-multiplier (d-SiPM) with focal plane detection of the center of mass position and dispersion of the scintillation light is presented. The d-SiPM shares the same off-chip time-to-digital converter such that each pixel can be individually connected to it. A miniature d-SiPM <inline-formula> <tex-math notation="LaTeX">$8\times 8$ </tex-math></inline-formula> single-photon avalanche-diode (SPAD) array has been fabricated as a proof of concept. The SPADs along each row and column are connected through an OR combination technique. It has <inline-formula> <tex-math notation="LaTeX">$256\times 256\mu \text{m}^{\mathrm { {2}}}$ </tex-math></inline-formula> without peripherals circuits and pads. The fill factor is about 11%. The average dark count rate of the mini d-SiPM is of 240 kHz. The average photon detection efficiency is 5% at 480 nm wavelength, room temperature, and 0.9 V excess voltage. The dynamic range is of 96 dB. The sensor array features a time resolution of 212 ps. The photon-timing SNR is 81 dB. The focal plane statistics of the light-spot has been proved as well by measurements.
Astrocyte cultures from human embryonic brain: Characterization and modulation of surface molecules by inflammatory cytokines

Astrocyte‐enriched cultures were established upon passaging of primary cultures from the myelencephalon and mesencephalon of 7–9‐week‐old human embryos. Immunocytochemical analysis showed that third‐fourth passage cultures were composed of a highly enriched population of proliferating, epithelioid cells, up to 90% of which expressed glial fibrillary acidic protein (GFAP); no macrophages and very few fibroblasts (>2%) were present. GFAP expression and proliferation declined upon further culturing in serum‐containing medium but could be transiently reinduced by growing the cells in a serum‐free chemically defined medium. Large numbers of GFAP+ astrocytes were obtained from each embryo and could be stored frozen and recultured.
Optimizing the Balance Between Task Automation and Human Manual Control in Simulated Submarine Track Management

Automation can improve operator performance and reduce workload, but can also degrade operator situation awareness (SA) and the ability to regain manual control. In 3 experiments, we examined the extent to which automation could be designed to benefit performance while ensuring that individuals maintained SA and could regain manual control. Participants completed a simulated submarine track management task under varying task load. The automation was designed to facilitate information acquisition and analysis, but did not make task decisions. Relative to a condition with no automation, the continuous use of automation improved performance and reduced subjective workload, but degraded SA. Automation that was engaged and disengaged by participants as required (adaptable automation) moderately improved performance and reduced workload relative to no automation, but degraded SA. Automation engaged and disengaged based on task load (adaptive automation) provided no benefit to performance or workload, and degraded SA relative to no automation. Automation never led to significant return-to-manual deficits. However, all types of automation led to degraded performance on a nonautomated task that shared information processing requirements with automated tasks. Given these outcomes, further research is urgently required to establish how to design automation to maximize performance while keeping operators cognitively engaged.