Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of high‐yield thrombocytapheresis on the quality of platelet products

BACKGROUND: The steadily increasing demands for single‐donor apheresis platelet (PLT) concentrates (APCs) are a challenge to the PLT supply system. Therefore, efforts to improve plateletpheresis yield, allowing apheresis products to be split into 2 or more units, are valuable strategies. No data to demonstrate in vivo transfusion efficacy of these high‐yield split‐APCs are currently available, however.
Disparities in access to liver transplantation in Spain

Background. The maintenance of an equitable system for access to transplantation is a matter of concern to all professionals involved in this field. Any national system must ensure equity. Methods. The rates of indication for liver transplantation have been reviewed for all Spanish regions. The time to transplantation was evaluated with respect to different recipient characteristics and donor rates. The indication rates for liver transplantation are similar in the different countries with liver transplant programs but are far from similar among different regions in Spain. This suggests that there is not equity in the access to liver transplantation. Results. A review of the factors affecting the waiting times to transplantation after being registered for the waiting list shows that some groups of patients are currently waiting less time than others. Shorter waiting times occur in patients of the AB group, children, patients with hepatocarcinoma, and patients living in the zone of Valencia, despite similar organ donation rates in all transplant zones. Conclusion. Neither the rate nor the probability of liver transplantation is affected exclusively by the organ donation rate in Spain but also depends on the number of patients admitted to the waiting list. Despite the existence of an organ allocation system that is center-oriented, liver patients are receiving grafts mainly based on the severity of the illness, because clearance rates from the waiting list of both dead patients and grafted patients are the same.
CD11c‐positive cells from brain, spleen, lung, and liver exhibit site‐specific immune phenotypes and plastically adapt to new environments

The brain's immune privilege has been also attributed to the lack of dendritic cells (DC) within its parenchyma and the adjacent meninges, an assumption, which implies maintenance of antigens rather than their presentation in lymphoid organs. Using mice transcribing the green fluorescent protein under the promoter of the DC marker CD11c (itgax), we identified a juxtavascular population of cells expressing this DC marker and demonstrated their origin from bone marrow and local microglia. We now phenotypically compared this population with CD11c/CD45 double‐positive cells from lung, liver, and spleen in healthy mice using seven‐color flow cytometry. We identified unique, site‐specific expression patterns of F4/80, CD80, CD86, CX3CR1, CCR2, FLT3, CD103, and MHC‐II. Furthermore, we observed the two known CD45‐positive populations (CD45high and CD45int) in the brain, whereas liver, lung, and spleen exhibited a homogeneous CD45high population. CD11c‐positive microglia lacked MHC‐II expression and CD45high/CD11c‐positive cells from the brain have a lower percentage of MHC‐II‐positive cells. To test whether phenotypical differences are fixed by origin or specifically develop due to environmental factors, we transplanted brain and spleen mononuclear cells on organotypic slice cultures from brain (OHSC) and spleen (OSSC). We demonstrate that adaption and ramification of MHC‐II‐positive splenocytes is paralleled by down‐regulation of MHC‐II, whereas brain‐derived mononuclear cells neither ramified nor up‐regulated MHC‐II in OSSCs. Thus, brain‐derived mononuclear cells maintain their MHC‐II‐negative phenotype within the environment of an immune organ. Intraparenchymal CD11c‐positive cells share immunophenotypical characteristics of DCs from other organs but remain unique for their low MHC‐II expression. GLIA 2015;63:611–625
Low‐frequency summation of synaptically activated transient receptor potential channel‐mediated depolarizations

Neurons sum their input by spatial and temporal integration. Temporally, presynaptic firing rates are converted to dendritic membrane depolarizations by postsynaptic receptors and ion channels. In several regions of the brain, including higher association areas, the majority of firing rates are low. For rates below 20 Hz, the ionotropic receptors α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptor and N‐methyl‐d‐aspartate (NMDA) receptor will not produce effective temporal summation. We hypothesized that depolarization mediated by transient receptor potential (TRP) channels activated by metabotropic glutamate receptors would be more effective, owing to their slow kinetics. On the basis of voltage‐clamp and current‐clamp recordings from a rat slice preparation, we constructed a computational model of the TRP channel and its intracellular activation pathway, including the metabotropic glutamate receptor. We show that synaptic input frequencies down to 3–4 Hz and inputs consisting of as few as three to five pulses can be effectively summed. We further show that the time constant of integration increases with increasing stimulation frequency and duration. We suggest that the temporal summation characteristics of TRP channels may be important at distal dendritic arbors, where spatial summation is limited by the number of concurrently active synapses. It may be particularly important in regions characterized by low and irregular rates.
M Types of Group A Streptococcal Isolates Submitted to the National Centre for Streptococcus (Canada) from 1993 to 1999

ABSTRACT The National Centre for Streptococcus (NCS) (Canada) determined the group A streptococcal (GAS) M types of 4,760 Canadian isolates submitted between 1993 and 1999 by classic serotyping. The 10 most frequently identified M types were M1 (26.4%), M12 (9.8%), M28 (8.9%), M3 (6.8%), M4 (6.2%), M11 (4.8%), M89 (3.1%), M6 (3.0%), M2 (2.6%), and M77 (1.9%). Nontypeable isolates accounted for 15.4% of the collection. The province of Ontario submitted 51.1% of the isolates, followed by Quebec (21.2%) and Alberta (13.9%). Together, these three provinces constituted 71.3% of the Canadian population in 1996. The numbers of M types M1, M12, M28, and M3 occurred most frequently in subjects whose ages were <1 to 15 years and 25 to 45 years, as well as in the elderly (60 to 90 years). Further analysis found that the four most frequently identified M types from blood, brain, and cerebrospinal fluid were M1 (28.2%), M28 (9.2%), M12 (9.1%), and M3 (8.2%), with 13.4% of isolates being nontypeable. The four isolates from throats most frequently identified were M1 (19.5%), M12 (15.3%), M3 (8.6%), and M28 (5%) with 19.4% of isolates being nontypeable. The sic gene of a subset of M1 strains (9.5% of the M1 collection) was sequenced. Of 36 sic types identified, the four most common were sic1.01 (22.8%), sic1.02 (14.9%), sic1.135 (10.5%), and sic1.178 (9.6%). Together these four sic types further characterized nearly 60% of the M1 strains sequenced. In summary, from the years 1993 to 1999, the NCS detected 54 M types, of which 10 different M types constituted 73.5% of the collection. M1 was the most common GAS M type circulating in the Canadian population, responsible for more than a quarter of the isolates typed. The most common throat isolates differed in M-type and proportion from those of invasive isolates. Sequencing the sic gene further characterized the most common M-type serotype 1 in a fashion that may be useful for epidemiologic investigations.
E-Participation and Czech Statutory Cities

Today, participation is often emphasized as an instrument for solving democratic deficit and low public trust in institutions that gained the power to regulate the life of a society. Attempts to increase the legitimacy of their purposes and goals are clearly visible. Ideas of ICT use for improving quality of government have been discussed and translated into practice intensively. Today, e-participation represents a single category in some e-government concepts. In compliance with the e-government movement, e-participation attempts to improve government by achieving better governance. The paper introduces results of web analysis focusing on e-participation instruments that can be found on websites of Czech statutory cities.
Influence of fatty acids on mitochondrial metabolism of adipocyte progenitors and endothelial cells

Context: In obesity, the cells are exposed to excessive amounts of nutrients, especially free fatty acids (FFAs) that induce a variety of metabolic changes. Objective: We investigated the effect of FFAs on the mitochondrial function in different cell populations under stress conditions. Methods: Human adipose tissue progenitor cells (SVF) or endothelial cells (HUVECs) were incubated with 30μM of selected saturated or unsaturated FFA for 24 h, at times supplemented with 5ng/mL tumour necrosis factor alpha (TNFα) for the last 4 h. Changes in oxygen respiration rate, mitochondrial membrane potential (mitoMP) and total ATP content were monitored. Results: Saturated palmitic acid demonstrated no effect, while a selection of unsaturated FFAs ameliorated metabolism of the progenitor SVF cells. TNFα either did not affect or nullified some of the favourable FFA-induced effects. Conclusions: The mitoMP was the most sensitive parameter reflecting positive impact of the unsaturated FFA on the adipose SVF cells’ metabolism.
genepop’007: a complete re‐implementation of the genepop software for Windows and Linux

This note summarizes developments of the genepop software since its first description in 1995, and in particular those new to version 4.0: an extended input format, several estimators of neighbourhood size under isolation by distance, new estimators and confidence intervals for null allele frequency, and less important extensions to previous options. genepop now runs under Linux as well as under Windows, and can be entirely controlled by batch calls.
Transfontanelle Ultra-Sonography: An Invaluable Tool in the Assessment of the Infant Brain

Transfontanelle (cranial) ultrasonography, was carried out in 98 Nigerian infants over a period of 5 years. Of the infants, 38 (38.8%) had hydrocephalus from various causes while 26 (25.5%) had congenital anomalies. As ultrasound equipment is becoming a more readily available and affordable tool in the developing countries, it should become much easier for medical staff in these countries to arrive at the correct diagnosis of intracranial diseases in infants.
Weakly-Supervised Neural Response Selection from an Ensemble of Task-Specialised Dialogue Agents

Dialogue engines that incorporate different types of agents to converse with humans are popular. However, conversations are dynamic in the sense that a selected response will change the conversation on-the-fly, influencing the subsequent utterances in the conversation, which makes the response selection a challenging problem. We model the problem of selecting the best response from a set of responses generated by a heterogeneous set of dialogue agents by taking into account the conversational history, and propose a \emph{Neural Response Selection} method. The proposed method is trained to predict a coherent set of responses within a single conversation, considering its own predictions via a curriculum training mechanism. Our experimental results show that the proposed method can accurately select the most appropriate responses, thereby significantly improving the user experience in dialogue systems.
Power-Law Distributions of Dynamic Cascade Failures in Power-Grid Models

Power-law distributed cascade failures are well known in power-grid systems. Understanding this phenomena has been done by various DC threshold models, self-tuned at their critical point. Here, we attempt to describe it using an AC threshold model, with a second-order Kuramoto type equation of motion of the power-flow. We have focused on the exploration of network heterogeneity effects, starting from homogeneous two-dimensional (2D) square lattices to the US power-grid, possessing identical nodes and links, to a realistic electric power-grid obtained from the Hungarian electrical database. The last one exhibits node dependent parameters, topologically marginally on the verge of robust networks. We show that too weak quenched heterogeneity, coming solely from the probabilistic self-frequencies of nodes (2D square lattice), is not sufficient for finding power-law distributed cascades. On the other hand, too strong heterogeneity destroys the synchronization of the system. We found agreement with the empirically observed power-law failure size distributions on the US grid, as well as on the Hungarian networks near the synchronization transition point. We have also investigated the consequence of replacing the usual Gaussian self-frequencies to exponential distributed ones, describing renewable energy sources. We found a drop in the steady state synchronization averages, but the cascade size distribution, both for the US and Hungarian systems, remained insensitive and have kept the universal tails, being characterized by the exponent τ≃1.8. We have also investigated the effect of an instantaneous feedback mechanism in case of the Hungarian power-grid.
Elevated levels of serum nitrate, a stable end product of nitric oxide, in women with pre‐eclampsia

Objectives Nitric oxide released from vascular endothelial cells is a potent vasodilator and inhibits platelet adhesion. It has been suggested that decreased nitric oxide production from dysfunctional endothelial cells is implicated in the pathophysiology of pre‐eclampsia. In this study evidence was sought for abnormal production of nitric oxide in pre‐eclamptic women.
Rapid Sediment Accumulation Results in High Methane Effluxes from Coastal Sediments

Globally, the methane (CH4) efflux from the ocean to the atmosphere is small, despite high rates of CH4 production in continental shelf and slope environments. This low efflux results from the biological removal of CH4 through anaerobic oxidation with sulfate in marine sediments. In some settings, however, pore water CH4 is found throughout the sulfate-bearing zone, indicating an apparently inefficient oxidation barrier for CH4. Here we demonstrate that rapid sediment accumulation can explain this limited capacity for CH4 removal in coastal sediments. In a saline coastal reservoir (Lake Grevelingen, The Netherlands), we observed high diffusive CH4 effluxes from the sediment into the overlying water column (0.2–0.8 mol m-2 yr-1) during multiple years. Linear pore water CH4 profiles and the absence of an isotopic enrichment commonly associated with CH4 oxidation in a zone with high rates of sulfate reduction (50–170 nmol cm-3 d-1) both suggest that CH4 is bypassing the zone of sulfate reduction. We propose that the rapid sediment accumulation at this site (~ 13 cm yr-1) reduces the residence time of the CH4 oxidizing microorganisms in the sulfate/methane transition zone (< 5 years), thus making it difficult for these slow growing methanotrophic communities to build-up sufficient biomass to efficiently remove pore water CH4. In addition, our results indicate that the high input of organic matter (~ 91 mol C m-2 yr-1) allows for the co-occurrence of different dissimilatory respiration processes, such as (acetotrophic) methanogenesis and sulfate reduction in the surface sediments by providing abundant substrate. We conclude that anthropogenic eutrophication and rapid sediment accumulation likely increase the release of CH4 from coastal sediments.
Changing the Substrate Reactivity of 2-Hydroxybiphenyl 3-Monooxygenase from Pseudomonas azelaica HBP1 by Directed Evolution*

The substrate reactivity of the flavoenzyme 2-hydroxybiphenyl 3-monooxygenase (EC 1.14.13.44, HbpA) was changed by directed evolution using error-prone PCR. In situ screening of mutant libraries resulted in the identification of proteins with increased activity towards 2-tert-butylphenol and guaiacol (2-methoxyphenol). One enzyme variant contained amino acid substitutions V368A/L417F, which were inserted by two rounds of mutagenesis. The double replacement improved the efficiency of substrate hydroxylation by reducing the uncoupled oxidation of NADH. With guaiacol as substrate, the two substitutions increasedVmax from 0.22 to 0.43 units mg−1protein and decreased the K′ m from 588 to 143 μm, improvingk′cat/K′ m by a factor of 8.2. With 2-tert-butylphenol as the substrate,k′cat was increased more than 5-fold. Another selected enzyme variant contained amino acid substitution I244V and had a 30% higher specific activity with 2-sec-butylphenol, guaiacol, and the “natural” substrate 2-hydroxybiphenyl. TheK′ m for guaiacol decreased with this mutant, but the K′ m for 2-hydroxybiphenyl increased. The primary structure of HbpA shares 20.1% sequence identity with phenol 2-monooxygenase from Trichosporon cutaneum. Structure homology modeling with this three-domain enzyme suggests that Ile244 of HbpA is located in the substrate binding pocket and is involved in accommodating the phenyl substituent of the phenol. In contrast, Val368 and Leu417 are not close to the active site and would not have been obvious candidates for modification by rational design.
Effect of selective blockade of endothelin ETB receptors on the liver dysfunction and injury caused by endotoxaemia in the rat

1 We investigated the effects of the selective endothelin (ET)A receptor antagonist BQ‐485 and the selective ETB receptor antagonist BQ‐788 on circulatory failure, multiple organ dysfunction syndrome (MODS) and the alterations in acid base balance caused by endotoxaemia in the anaesthetized rat. 2 Male Wistar rats were anaesthetized (thiopentone sodium; 120 mg kg−1, i.p.) and received a continuous infusion of vehicle (saline, 0.6 ml kg−1h−1, i.v.), BQ‐485 (10 nmol kg−1 min−1, i.v.) or BQ‐788 (10 nmol kg−1 min−1, i.v.). Fifteen min later, animals received a bolus injection of either saline (0.9% NaCl, 1 ml kg−1, i.v.) or E. coli lipopolysaccharide (LPS, 10 mg kg−1, i.v.). 3 Injection of LPS resulted in a fall in blood pressure from 115 ± 4 mmHg (time 0) to 82 ± 4 mmHg at 360 min (n = 15) as well as a hyporeactivity to the pressor responses to noradrenaline (NA, 1 μm kg−1, i.v.). Infusion of BQ‐788 attenuated the delayed hypotension (at 360 min: 100 ± 4 mmHg, n = 7; P < 0.05) and significantly enhanced the pressor responses elicited by NA (at 60 to 240 min). In contrast, treatment of LPS‐rats with BQ‐485 augmented the hypotension (at 360 min), but did not affect the vascular hyporeactivity elicited by endotoxaemia. 4 Endotoxaemia for 360 min resulted in rises in the serum levels of urea and creatinine (indicators of renal failure), glutamate‐oxalate‐transferase (GOT) and glutamate‐pyruvate‐transferase (GPT) (indicators of hepatocellular injury), and bilirubin and γ‐glutamyl transferase (γGT) (indicators of liver failure) as well as nitrite (indicator of the induction of nitric oxide synthase; iNOS). Treatment of LPS‐rats with BQ‐788, but not with BQ‐485, attenuated the degree of liver injury and failure, while neither BQ‐788 nor BQ‐485 affected the acute renal failure or the induction of iNOS caused by endotoxin. 5 Endotoxaemia also caused (within 15 min) an acute metabolic acidosis (falls in pH, HCO3− and base excess) which was compensated by hyperventilation (fall in Paco2). Treatment of LPS‐rats with BQ‐788 or BQ‐485 did not affect the metabolic acidosis caused by LPS. 6 Thus, the selective ETB receptor antagonist BQ‐788 attenuated (i) the delayed hypotension, (ii) the vascular hyporeactivity to NA as well as (iii) the degree of hepatocellular injury and dysfunction caused by endotoxin in the anaesthetized rat. In contrast, the selective ETA receptor antagonist did neither attenuate the circulatory failure nor the liver or renal dysfunction associated with endotoxaemia. We propose that the prevention of the hepatocellular dysfunction and injury caused BQ‐788 in endotoxaemia is due to an improvement in oxygen delivery to the liver secondary to (i) inhibition of pre‐sinusoidal constriction, (ii) inhibition of sinusoidal constriction, and (iii) improvement in perfusion pressure.
Structural insights into the assembly of the histone deacetylase-associated Sin3L/Rpd3L corepressor complex

Significance Gene transcription in eukaryotes is regulated by enzymes that posttranslationally add or remove acetyl groups from histones and render the underlying DNA more or less accessible to the transcription machinery. How histone deacetylases (HDACs), the enzymes responsible for deacetylation that are commonly found in multiprotein complexes, are assembled and targeted to their sites of action to affect transcription repression is largely unknown. We show biochemically and structurally how two key subunits of a conserved HDAC complex recruit multiple copies of HDACs into the complex in a manner that allows the enzymes to explore a large conformational space when the complex is targeted to specific genomic loci. This complex seems to be tailored for efficient deacetylation of nucleosomes that are situated far apart. Acetylation is correlated with chromatin decondensation and transcriptional activation, but its regulation by histone deacetylase (HDAC)-bearing corepressor complexes is poorly understood. Here, we describe the mechanism of assembly of the mammalian Sin3L/Rpd3L complex facilitated by Sds3, a conserved subunit deemed critical for proper assembly. Sds3 engages a globular, helical region of the HDAC interaction domain (HID) of the scaffolding protein Sin3A through a bipartite motif comprising a helix and an adjacent extended segment. Sds3 dimerizes through not only one of the predicted coiled-coil motifs but also, the segment preceding it, forming an ∼150-Å-long antiparallel dimer. Contrary to previous findings in yeast, Sin3A rather than Sds3 functions in recruiting HDAC1 into the complex by engaging the latter through a highly conserved segment adjacent to the helical HID subdomain. In the resulting model for the ternary complex, the two copies of the HDACs are situated distally and dynamically because of a natively unstructured linker connecting the dimerization domain and the Sin3A interaction domain of Sds3; these features contrast with the static organization described previously for the NuRD (nucleosome remodeling and deacetylase) complex. The Sds3 linker features several conserved basic residues that could potentially maintain the complex on chromatin by nonspecific interactions with DNA after initial recruitment by sequence-specific DNA-binding repressors.