Miracle-dz/UniFAR-FTUs huggingface dataset:
Increased vascular responsiveness to α2-adrenergic stimulation during NOS inhibition-induced hypertension.

Increased vascular resistance during systemic nitric oxide synthase (NOS) inhibition is dependent on adrenergic vasoconstriction. This study tested the hypothesis that increased vascular sensitivity to adrenergic agonists contributes to this vasoconstriction. Superior mesenteric arteries and thoracic aortae from male Sprague-Dawley rats drinking water containing N ω-nitro-l-arginine (l-NNA; 14 days, 60 mg ⋅ kg-1 ⋅ day-1) and control rats were cut into helical strips, and endothelium was removed for contractile experiments.l-NNA arteries were more sensitive to UK-14304 (α2-adrenergic agonist) and norepinephrine (NE), whereas responses to phenylephrine (PE) were not different [concentration causing 50% maximal response (EC50),l-NNA vs. control: UK-14304, 0.071 vs. 0.71 μmol/l; NE, 1.15 vs. 9.95 nmol/l]. Yohimbine, an α2-selective antagonist, caused a concentration-dependent inhibition of contraction to NE only inl-NNA arteries (EC50 = 6.3 vs. 1.6 nmol/l at 1 nmol/l yohimbine), whereas prazosin shifted NE curves similarly in arteries from both groups. Yohimbine (10 nmol/l) inhibited contractions to UK-14304 (EC50 = 59 μmol/l vs. 17 μmol/l) but not contractions to PE, whereas prazosin inhibited both. These data indicate thatl-NNA-induced hypertension leads to increased sensitivity of prazosin-sensitive α2-adrenoceptors, an upregulation that could cause the increased vasoconstrictor response to NE in this model of hypertension.
Ouabain Protects Human Renal Cells against the Cytotoxic Effects of Shiga Toxin Type 2 and Subtilase Cytotoxin

Hemolytic uremic syndrome (HUS) is one of the most common causes of acute renal failure in children. The majority of cases are associated with Shiga toxin (Stx)-producing Escherichia coli (STEC). In Argentina, HUS is endemic and presents the highest incidence rate in the world. STEC strains expressing Stx type 2 (Stx2) are responsible for the most severe cases of this pathology. Subtilase cytotoxin (SubAB) is another STEC virulence factor that may contribute to HUS pathogenesis. To date, neither a licensed vaccine nor effective therapy for HUS is available for humans. Considering that Ouabain (OUA) may prevent the apoptosis process, in this study we evaluated if OUA is able to avoid the damage caused by Stx2 and SubAB on human glomerular endothelial cells (HGEC) and the human proximal tubule epithelial cell (HK-2) line. HGEC and HK-2 were pretreated with OUA and then incubated with the toxins. OUA protected the HGEC viability from Stx2 and SubAB cytotoxic effects, and also prevented the HK-2 viability from Stx2 effects. The protective action of OUA on HGEC and HK-2 was associated with a decrease in apoptosis and an increase in cell proliferation. Our data provide evidence that OUA could be considered as a therapeutic strategy to avoid the renal damage that precedes HUS.
Inflammation and autoimmunity in pulmonary hypertension: is there a role for endothelial adhesion molecules? (2017 Grover Conference Series)

While pulmonary hypertension (PH) has traditionally not been considered as a disease that is directly linked to or, potentially, even caused by inflammation, a rapidly growing body of evidence has demonstrated the accumulation of a variety of inflammatory and immune cells in PH lungs, in and around the wall of remodeled pulmonary resistance vessels and in the vicinity of plexiform lesions, respectively. Concomitantly, abundant production and release of various inflammatory mediators has been documented in both PH patients and experimental models of PH. While these findings unequivocally demonstrate an inflammatory component in PH, they have fueled an intense and presently ongoing debate as to the nature of this inflammatory aspect: is it a mere bystander of or response to the actual disease process, or is it a pathomechanistic contributor or potentially even a trigger of endothelial injury, smooth muscle hypertrophy and hyperplasia, and the resulting lung vascular remodeling? In this review, we will discuss the present evidence for an inflammatory component in PH disease with a specific focus on the potential role of the endothelium in this scenario and highlight future avenues of experimental investigation which may lead to novel therapeutic interventions.
Parameter Optimization of PID Controller Based on Quantum-behaved Particle Swarm Optimization Algorithm

The conventional parameter optimisation of PID controller is easy to produce surge and big overshoot, and therefore heuristics such as genetic algorithm (GA), particle swarm optimisation (PSO) are employed to enhance the capability of traditional techniques. But the major problem of these algorithms is that they may be trapped in the local optima of the objective and lead to poor performance. In this paper, a quantum-behaved particle swarm optimisation (QPSO) for the parameter optimisation of PID controller is proposed from sub-optimal perspective. This method is very advantageous for practical control systems. Three examples are given to illustrate the design procedure and exhibit the effectiveness of the proposed method via a comparison study with an existing Z-N, GA and PSO approaches
A comparative study on characterisations of Cissus quadrangularis and Phoenix reclinata natural fibres

The morphological, physicochemical, mechanical and thermal properties of Veldt-grape stem fibre and wild date palm leaf stalk fibre are described in this work, which are seldom studied before. The botanical name of Veldt-grape stem fibre and wild date palm leaf stalk fibre are known as Cissus quadrangularis and Phoenix reclinata, respectively. The morphological analysis of vegetable fibres showed the presence of cracks, microvoids and impurities on the surfaces of Veldt-grape stem fibre and wild date palm leaf stalk fibre. Veldt-grape stem fibre possessed the lowest diameter and density of approximately 0.2668 mm and 1.2128 g/cm3, respectively, compared to wild date palm leaf stalk fibre. An X-ray diffraction and Fourier transform infrared analysis of Veldt-grape stem fibre and wild date palm leaf stalk fibre exhibited the presence of cellulose Iβ with a crystallinity index of 30.9% and 38.8%, respectively. Wild date palm leaf stalk fibre contained high surface roughness in the range of 0.904 µm than Veldt-grape stem fibre (0.611 µm). Tensile tests displayed that wild date palm leaf stalk fibre has highest tensile strength of around 66 MPa, and Veldt-grape stem fibre has highest strain to failure of around 6% in comparison with other fibre. The thermogravimetric analysis indicates that thermal stability of Veldt-grape stem fibre and wild date palm leaf stalk fibre is better up to 230℃ and 250℃, respectively, which are well within the polymerisation process temperature.
Soluble Urokinase Receptor and Chronic Kidney Disease.

BACKGROUND Relatively high plasma levels of soluble urokinase-type plasminogen activator receptor (suPAR) have been associated with focal segmental glomerulosclerosis and poor clinical outcomes in patients with various conditions. It is unknown whether elevated suPAR levels in patients with normal kidney function are associated with future decline in the estimated glomerular filtration rate (eGFR) and with incident chronic kidney disease. METHODS We measured plasma suPAR levels in 3683 persons enrolled in the Emory Cardiovascular Biobank (mean age, 63 years; 65% men; median suPAR level, 3040 pg per milliliter) and determined renal function at enrollment and at subsequent visits in 2292 persons. The relationship between suPAR levels and the eGFR at baseline, the change in the eGFR over time, and the development of chronic kidney disease (eGFR <60 ml per minute per 1.73 m(2) of body-surface area) were analyzed with the use of linear mixed models and Cox regression after adjustment for demographic and clinical variables. RESULTS A higher suPAR level at baseline was associated with a greater decline in the eGFR during follow-up; the annual change in the eGFR was -0.9 ml per minute per 1.73 m(2) among participants in the lowest quartile of suPAR levels as compared with -4.2 ml per minute per 1.73 m(2) among participants in the highest quartile (P<0.001). The 921 participants with a normal eGFR (≥ 90 ml per minute per 1.73 m(2)) at baseline had the largest suPAR-related decline in the eGFR. In 1335 participants with a baseline eGFR of at least 60 ml per minute per 1.73 m(2), the risk of progression to chronic kidney disease in the highest quartile of suPAR levels was 3.13 times as high (95% confidence interval, 2.11 to 4.65) as that in the lowest quartile. CONCLUSIONS An elevated level of suPAR was independently associated with incident chronic kidney disease and an accelerated decline in the eGFR in the groups studied. (Funded by the Abraham J. and Phyllis Katz Foundation and others.).
Developing a hippocampal neural prosthetic to facilitate human memory encoding and recall

Objective. We demonstrate here the first successful implementation in humans of a proof-of-concept system for restoring and improving memory function via facilitation of memory encoding using the patient’s own hippocampal spatiotemporal neural codes for memory. Memory in humans is subject to disruption by drugs, disease and brain injury, yet previous attempts to restore or rescue memory function in humans typically involved only nonspecific, modulation of brain areas and neural systems related to memory retrieval. Approach. We have constructed a model of processes by which the hippocampus encodes memory items via spatiotemporal firing of neural ensembles that underlie the successful encoding of short-term memory. A nonlinear multi-input, multi-output (MIMO) model of hippocampal CA3 and CA1 neural firing is computed that predicts activation patterns of CA1 neurons during the encoding (sample) phase of a delayed match-to-sample (DMS) human short-term memory task. Main results. MIMO model-derived electrical stimulation delivered to the same CA1 locations during the sample phase of DMS trials facilitated short-term/working memory by 37% during the task. Longer term memory retention was also tested in the same human subjects with a delayed recognition (DR) task that utilized images from the DMS task, along with images that were not from the task. Across the subjects, the stimulated trials exhibited significant improvement (35%) in both short-term and long-term retention of visual information. Significance. These results demonstrate the facilitation of memory encoding which is an important feature for the construction of an implantable neural prosthetic to improve human memory.
Egg Load Evolution in Parasitoids

Parasitic wasps lay their eggs in or on other insects. Allocation of resources to reproduction (eggs) and survival (life span) should maximize reproductive success, but stochasticity in the number of hosts encountered precludes an exact match of allocation with reproductive opportunity. We study optimal egg loads using a general model for pro‐ovigenic parasitoids (which only mature eggs before adult life) and a dynamic programming model for synovigenic parasitoids (which can mature additional eggs during adult life). We find that stochasticity has a major effect on optimal egg loads and that the patchy distribution of hosts is the major source of stochasticity in reproductive opportunities. In a stochastic world, the further “relative habitat quality” (expected number of oviposition opportunities gained by reducing reproductive investment by one egg) is below unity (as we argue it generally is), the more the optimal egg load exceeds the expected number of hosts. In unusually rich environments, however, stochasticity decreases optimal egg loads. Although synovigenic parasitoids can adjust to the conditions they encounter, they too have to invest for an uncertain future. Because they can replenish their egg supply throughout life, the incidence of egg limitation is even lower than in pro‐ovigenic parasitoids.
Redistribution of Na+/H+ exchanger isoform NHE3 in proximal tubules induced by acute and chronic hypertension.

Redistribution of apical Na+/H+exchangers (NHE) in the proximal tubules as a plausible mechanism of pressure natriuresis was investigated with confocal immunofluorescence microscopy in Sprague-Dawley rats (SD), spontaneously hypertensive rats (SHR), and two-kidney, one-clip Goldblatt hypertensive rats (GH). NHE isoform NHE3 was localized in the brush border of proximal tubules in SD. Twenty minutes of induced acute hypertension (20-40 mmHg) resulted in a pronounced redistribution of isoform NHE3 from the brush border into the base of microvilli, where clathrin-coated pits were localized. Prehypertensive young SHR (5 wk old, mean blood pressure 105 ± 3 mmHg, n = 11) produced similar findings. However, NHE3 was found to concentrate in the base of microvilli in adult SHR (12 wk old, mean blood pressure 134 ± 6 mmHg, n = 12) and nonclipped kidneys of GH (mean blood pressure 131 ± 6 mmHg, n = 6). In clipped kidneys of GH, which were not exposed to the hypertension because of the arterial clips, NHE3 was localized on the brush border as in normal SD. No further redistribution of NHE3 was detected in adult SHR or GH when acute hypertension was induced. Since both acute and chronic increase of arterial pressure can provoke the redistribution of apical NHE in proximal tubules, the pressure-induced NHE redistribution could be a physiological response and an integral part of pressure natriuresis.
Phonological processing in children with specific language impairment with and without reading difficulties.

BACKGROUND Specific language impairment (SLI) is heterogeneous and identifying subgroups within it may help explain the aetiology of the condition. Phonological processing abilities distinguish between children with SLI who do and do not have reading decoding impairments (RDIs). AIMS To probe different levels of phonological processing in children with SLI with and without RDI to investigate the cognitive basis of these differences. METHODS & PROCEDURES A total of 64 children aged 5-17 years were classified using the results of standardized language and single-word reading tests into those with no SLI and no RDI (No SLI/No RDI) (N = 18), no SLI but with RDI (No SLI/RDI) (N = 4, not included in analyses because of the small number), SLI/No RDI (N = 20), and SLI/RDI (N = 22). The groups were compared on a range of tasks engaging different levels of phonological processing (input and output processing and phonological awareness). OUTCOMES & RESULTS The SLI/RDI group was distinguished from the SLI/No RDI and No SLI/No RDI groups by more errors in the longer items in non-word repetition and by poorer phonological awareness. Non-word discrimination scores indicated a gradient of performance across groups that was not associated with a qualitatively different pattern of performance. CONCLUSIONS & IMPLICATIONS This is the first study contrasting input and output processes associated with phonological processing. The results suggest that deficits in SLI plus RDI may be associated with impairment in actively maintaining phonological representations for phonological processing, which is not present in those without RDI and which leads to reading decoding difficulties.
Transmural heterogeneity of action potentials and I to1 in myocytes isolated from the human right ventricle.

Limited information is available about transmural heterogeneity in cardiac electrophysiology in man. The present study was designed to evaluate heterogeneity of cardiac action potential (AP), transient outward K+ current ( I to1) and inwardly rectifying K+ current ( I K1) in human right ventricle. AP and membrane currents were recorded using whole cell current- and voltage-clamp techniques in myocytes isolated from subepicardial, midmyocardial, and subendocardial layers of the right ventricle of explanted failing human hearts. AP morphology differed among the regional cell types. AP duration (APD) at 0.5-2 Hz was longer in midmyocardial cells (M cells) than in subepicardial and subendocardial cells. At room temperature, observed I to1, on step to +60 mV, was significantly greater in subepicardial (6.9 ± 0.8 pA/pF) and M cells (6.0 ± 1.1 pA/pF) than in subendocardial cells (2.2 ± 0.7 pA/pF, P < 0.01). Slower recovery of I to1 was observed in subendocardial cells. The half-inactivation voltage of I to1 was more negative in subendocardial cells than in M and subepicardial cells. At 36°C, the density of I to1 increased, the time-dependent inactivation and reactivation accelerated, and the frequency-dependent reduction attenuated in all regional cell types. No significant difference was observed in I K1 density among the regional cell types. The results indicate that M cells in humans, as in canines, show the greatest APD and that a gradient of I to1 density is present in the transmural ventricular wall. Therefore, the human right ventricle shows significant transmural heterogeneity in AP morphology and I to1properties.
Enteroparasites in Riverside Settlements in the Pantanal Wetlands Ecosystem

Background Intestinal parasites are a major source of health problems in developing countries, where socioeconomic, cultural, and environmental conditions contribute in maintaining the biological cycles of various parasites and facilitating their spread. The objective of this study, conducted in Corumbá, Mato Grosso do Sul state, Brazil, was to investigate the occurrence of intestinal parasites in riverside communities in the South Pantanal wetlands and conduct educational interventions focused on health and environmental preservation. Method In total, 196 stool samples were tested for parasites using the merthiolate-iodine-formaldehyde concentration (MIFC) technique and spontaneous sedimentation and educational activities were carried out. Results Enteroparasite prevalence was 72% (65.6–78.2%; 95% CI). Of the 141 positive cases, monoparasitism was found in 34.7%, biparasitism in 23%, and polyparasitism in 14.3%. Entamoeba coli was the most frequent protozoan (70.2%). Among helminths, hookworms were the most prevalent. Enteroparasitosis prevalence did not differ for sex or place of abode but proved higher in individuals older than 10 years. Conclusion The high positivity rate for enteroparasites found for the communities stems from lack of sanitation and poor personal and environmental hygiene habits, indicating that effective health policies and educational interventions are needed to reduce the current risk levels.
Peptidergic and cholinergic neurons and mediators in peptone-induced gastroprotection: role of cyclooxygenase-2.

This study investigates the neural pathways, mediators, and cyclooxygenase isoenzymes involved in the gastroprotection conferred by peptone in rats. Intragastric perfusion with 8% peptone protected against gross and histological damage induced by subsequent perfusion with 50% ethanol. The gastroprotective effect of peptone was near maximally inhibited by gastrin immunoneutralization, inactivation of capsaicin-sensitive afferent neurons, calcitonin gene-related peptide (CGRP) immunoneutralization, blockade of gastrin receptors, CGRP, bombesin/gastrin-releasing peptide (GRP), or somatostatin receptors, and by the nitric oxide (NO) synthase inhibitor N G-nitro-l-arginine methyl ester and was partially (46%) counteracted by atropine. Indomethacin and the selective cyclooxygenase-2 inhibitors NS-398 and L-745,337 dose dependently (50% inhibitory dose, 4.2, 0.8, and 1.5 mg/kg, respectively) attenuated the peptone-induced protection. Dexamethasone was ineffective. These results indicate that protective effects of peptone involve endogenous gastrin and possibly somatostatin and are mediated by capsaicin-sensitive afferent, cholinergic, and bombesin/GRP neurons. CGRP, NO, and prostaglandins participate as essential mediators. The study provides evidence that prostaglandins derived from a constitutive cyclooxygenase-2 contribute to mucosal defense in the presence of ulcerogens and thus participate in homeostatic functions of the stomach.
POSTER PRESENTATION Open Access

number of unobserved words), and show that the posterior mean can be efficiently computed via a simple numerical integral. The second estimator incorporates the prior knowledge about the spike trains. We use a simple Bernoulli process as a parametric model of the spike trains, and use a Dirichlet process to allow arbitrary deviation from the Bernoulli process. Under this model, very sparse spike trains are a priori orders of magnitude more likely than those with many spikes. Both estimators are computationally efficient, and statistically consistent. We applied those estimators to spike trains from early visual system to quantify neural coding characteristics.
Reliability of algorithmic somatic copy number alteration detection from targeted capture data

Motivation: Whole exome and gene panel sequencing are increasingly used for oncological diagnostics. To investigate the accuracy of SCNA detection algorithms on simulated and clinical tumor samples, the precision and sensitivity of four SCNA callers were measured using 50 simulated whole exome and 50 simulated targeted gene panel datasets, and using 119 TCGA tumor samples for which SNP array data were available. Results: On synthetic exome and panel data, VarScan2 mostly called false positives, whereas Control‐FREEC was precise (>90% correct calls) at the cost of low sensitivity (<40% detected). ONCOCNV was slightly less precise on gene panel data, with similarly low sensitivity. This could be explained by low sensitivity for amplifications and high precision for deletions. Surprisingly, these results were not strongly affected by moderate tumor impurities; only contaminations with more than 60% non‐cancerous cells resulted in strongly declining precision and sensitivity. On the 119 clinical samples, both Control‐FREEC and CNVkit called 71.8% and 94%, respectively, of the SCNAs found by the SNP arrays, but with a considerable amount of false positives (precision 29% and 4.9%). Discussion: Whole exome and targeted gene panel methods by design limit the precision of SCNA callers, making them prone to false positives. SCNA calls cannot easily be integrated in clinical pipelines that use data from targeted capture‐based sequencing. If used at all, they need to be cross‐validated using orthogonal methods. Availability and implementation: Scripts are provided as supplementary information. Contact: gunther.jansen@molecularhealth.com Supplementary information: Supplementary data are available at Bioinformatics online.