Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Sertraline and Fluoxetine on P-Glycoprotein at Barrier Sites: In Vivo and In Vitro Approaches

Background and Purpose Retention of substances from systemic circulation in the brain and testes are limited due to high levels of P-glycoprotein (P-gp) in the luminal membranes of brain and testes capillary endothelial cells. From a clinical perspective, P-gp rapidly extrudes lipophilic therapeutic agents, which then fail to reach efficacious levels. Recent studies have demonstrated that acute administration of selective serotonin reuptake inhibitors (SSRI) can affect P-gp function, in vitro and in vivo. However, little is known concerning the time-course of these effects or the effects of different SSRI in vivo. Experimental Approach The P-gp substrate, tritiated digoxin ([3H] digoxin), was co-administered with fluoxetine or sertraline to determine if either compound increased drug accumulation within the brains and testes of mice due to inhibition of P-gp activity. We undertook parallel studies in endothelial cells derived from brain microvessels to determine the dose-response and time-course of effects. Key Results In vitro, sertraline resulted in rapid and potent inhibition of P-gp function in brain endothelial cells, as determined by cellular calcein accumulation. In vivo, a biphasic effect was demonstrated. Brain accumulation of [3H] digoxin was increased 5 minutes after treatment with sertraline, but by 60 minutes after sertraline treatment, brain accumulation of digoxin was reduced compared to control. By 240 minutes after sertraline treatment brain digoxin accumulation was elevated compared to control. A similar pattern of results was obtained in the testes. There was no significant effect of fluoxetine on P-gp function, in vitro or in vivo. Conclusions and Implications Acute sertraline administration can modulate P-gp activity in the blood-brain barrier and blood-testes barrier. This clearly has implications for the ability of therapeutic agents that are P-gp substrates, to enter the brain when co-administered with SSRI.
Egg sac structure and further biological observations in Comaroma simonii 1 Bertkau (Araneae, Anapidae)

Specimens of Comaroma simonii Bertkau from Styria (Austria) were kept in the laboratory in order to investigate biological details. Egg sacs were built at the end of June and the beginning of July. They were white-coloured, round in shape with a diameter of 1.47 mm on the average (n = 5) and were attached to vertical surfaces. Each egg sac contained three eggs of pale yellow colour. Normally the egg sac is protected by a silken funnel ending in a tube that points toward the ground underneath. It is assumed that this functions as a means of protection against egg predators and parasites. Spiderlings hatched after 27 days; they most probably moulted twice before leaving the cocoon on the 35th day. They built webs closely resembling those of the adults. Juveniles and sub adults showed no sclerotization of the body and were rarely found in the natural.habitat. There, vertical and horizontal migrations probably occur as a means of avoiding wetness or drying out, respectively. The sex ratio of all collected specimens was 98 females to 54 males. C. simonii is regarded as a 'k-strategist' and an eurychronous species.
Body Mass Index (BMI) Is Associated with Microalbuminuria in Chinese Hypertensive Patients

There is no general consensus on possible factors associated with microalbuminuria in hypertensive patients nor any reported study about this issue in Chinese patients. To examine this issues, 944 hypertensive patients were enrolled in a study based on a cross-sectional survey conducted in Southern China. Multivariate regression analyses were performed to identify the factors related with the presence of microalbuminuria and urinary excretion of albumin. The prevalence of microalbuminuria in hypertensive and non-diabetic hypertensive patients were 17.16% and 15.25%, respectively. Body mass index (BMI), but not waist circumference (WC), were independently associated with microalbuminuria and the values of urinary albumin to creatinine ratio (ACR) based on multiple regression analyses, even after excluding diabetic patients and patients taking inhibitors of the renin-angiotensin system from the analyses. Furthermore, patients with obesity (BMI ≥28) had higher levels of ACR, compared with those with normal weight (BMI <24 kg/m2) and overweight (24 kg/m2≤ BMI < 28). In conclusion, BMI, as a modifiable factor, is closely associated with microalbuminuria among Chinese hypertensive patients, which may provide a basis for future development of intervention approaches for these patients.
Emotional and physical health benefits of expressive writing

Writing about traumatic, stressful or emotional events has been found to result in improvements in both physical and psychological health, in non-clinical and clinical populations. In the expressive writing paradigm, participants are asked to write about such events for 15–20 minutes on 3–5 occasions. Those who do so generally have significantly better physical and psychological outcomes compared with those who write about neutral topics. Here we present an overview of the expressive writing paradigm, outline populations for which it has been found to be beneficial and discuss possible mechanisms underlying the observed health benefits. In addition, we suggest how expressive writing can be used as a therapeutic tool for survivors of trauma and in psychiatric settings.
Environment and structure influence on DNA conduction

Results for transmission through the $\mathrm{poly}{G}$ DNA molecule are presented. We show that (i) periodically arranged sodium counterions in close proximity to dry DNA give rise to a conduction channel, and aperiodicity in the counterion sequence can lead to a significant reduction in conduction, (ii) modification of the rise of B-DNA induces a change in the width of the transmission window, and (iii) specifically designed sequences are predicted to show intrinsic resonant tunneling behavior.
Densities and Derived Thermodynamic Properties of Imidazolium-, Pyridinium-, Pyrrolidinium-, and Piperidinium-Based Ionic Liquids

In the present work, experimental density measurements are reported along with the derived thermodynamic properties, such as the isothermal compressibility (κT), the isobaric expansivity (αp), and the thermal pressure coefficient (γv) for imidazolium-, pyridinium-, pyrrolidinium-, and piperidinium-based ionic liquids (ILs), namely, 1-ethyl-3-methylimidazolium trifluoromethanesulfonate [C2mim][CF3SO3], 3-methyl-1-propylpyridinium bis(trifluoromethylsulfonyl)imide [C3mpy][NTf2], 1-methyl-1-propylpyrrolidinium bis(trifluoromethylsulfonyl)imide [C3mpyr][NTf2], 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide [C4mpyr][NTf2], and 1-methyl-1-propylpiperidinium bis(trifluoromethylsulfonyl)imide [C3mpip][NTf2] in the pressure (0.10 < P/MPa < 35.00) and temperature (293.15 < T/K < 393.15) domains. These ILs were chosen to provide an understanding of the influence of the cation and anion on the properties under study. Experimental densities are correlated with the Tait equation with an average absolut.
Neutral and acidic oligosaccharides in preterm infants: a randomized, double-blind, placebo-controlled trial.

BACKGROUND Serious infectious morbidity is high in preterm infants. Enteral supplementation of prebiotics may reduce the incidence of serious infections, especially infections related to the gastrointestinal tract. OBJECTIVE The objective was to determine the effect of enteral supplementation of a prebiotic mixture consisting of neutral oligosaccharides ((SC)GOS/(LC)FOS) and acidic oligosaccharides (AOS) on serious infectious morbidity in preterm infants. DESIGN In a randomized controlled trial, preterm infants (gestational age <32 wk and/or birth weight <1500 g) received enteral supplementation of 80% (SC)GOS/(LC)FOS and 20% AOS (1.5 g . kg(-1) . d(-1)) or placebo (maltodextrin) between days 3 and 30 of life. Serious infectious morbidity was defined as a culture positive for sepsis, meningitis, pyelonephritis, or pneumonia. The analysis was performed by intention-to-treat and per-protocol, defined as > or =50% supplementation dose during the study period. RESULTS In total, 113 preterm infants were included. Baseline and nutritional characteristics were not different between groups. In the intention-to-treat analysis, the incidence of > or =1 serious infection, > or =1 serious endogenous infection, or > or =2 serious infectious episodes was not significantly different in the (SC)GOS/(LC)FOS/AOS-supplemented and placebo groups. In the per-protocol analysis, there was a trend toward a lower incidence of > or =1 serious endogenous infection and > or =2 serious infectious episodes in the (SC)GOS/(LC)FOS/AOS-supplemented group than in the placebo group (P = 0.09 and P = 0.07, respectively). CONCLUSIONS Enteral supplementation of (SC)GOS/(LC)FOS/AOS does not significantly reduce the risk of serious infectious morbidity in preterm infants. However, there was a trend toward a lower incidence of serious infectious morbidity, especially for infections with endogenous bacteria. This finding suggests a possible beneficial effect that should be evaluated in a larger study. This trial was registered at isrctn.org as ISRCTN16211826.
Sources of developmental change in pragmatic inferences about scalar terms

Pragmatic implicatures—inferences that weak statements imply that stronger ones could not be used—are a popular case study of children’s pragmatic development. A growing literature suggests that children make implicatures under certain conditions, but their performance varies widely across tasks, and few datasets allow direct comparisons between implicature types. We designed a simple paradigm to address these issues. In Experiment 1, we included both ad-hoc (contextual) and scalar (quantifier) descriptions and found that 4-year-olds were at ceiling in ad-hoc trials but had difficulty with scalar implicatures. In Experiment 2, 4-year-olds’ performance increased when we included only scalar trials, but was still low. Across both datasets, performance for “some” and “none” quantifiers was positively correlated. Our work provides more precise developmental data on the emergence of different implicature computations and illustrates that preschoolers’ recognition of implicatures relates both to their comprehension of particular lexical items and also their recognition of relevant alternatives.
Incidence and Measures to Prevent Intradialytic Hypotension in Patients on Maintenance Hemodialysis in a Tertiary Care Centre in India

Objective: Hypotension is quite common in any dialysis unit and despite significant improvements of hemodialysis techniques in the recent years; the frequency of recurrent intradialytic hypotension episodes has remained nearly unchanged. Our study is aimed to define the pathogenesis of intradialytic hypotension and attempts to describe effective measures for the hypotension prone hemodialysis patients on an individual basis. Design: This is a prospective study of 100 hemodialysis patients observed over 12 months at the Lilavati Hospital and Research Centre, Mumbai, India. Subjects with more than two episodes/month of hypotension on dialysis were diagnosed as having IDH. Results: Intradialytic hypotension was found in 18% of subjects. Incorrectly assessed ideal body weight was found to be the commonest cause of intradialytic hypotension. Volume assessment and adjusting the ideal body weight was found to be central to the problem of preventing intradialytic hypotension. Conclusion: This study shows that intradialytic hypotension is a common phenomenon, even in a tertiary care centre. Preventive strategies should be developed in each unit to decrease the future risk for intradialytic hypotension in specific patients.
Electrohydrodynamic Atomization for Improved Macromolecular Drug Delivery

With advances in drug research, the use of biological therapeutics is becoming a reality. Unfortunately, methods for processing and delivering these fragile macromolecules often limit their therapeutic potential. For this dissertation, we explore the aerosolization of macromolecules by way of electrohydrodynamic atomization (EHDA) and how this method can be used to process and deliver therapeutics. EHDA employs a high voltage to break a column of liquid into drops. It was unknown if or how the residual charge left of the resulting droplets would affect lung cells. An in vitro experiment was conducted to spray aerosolized DNA, by way of EHDA, onto human derived lungs cells to test for immunogenic and toxic effects. The lung cells displayed no immunogenic or toxic response to the DNA or high voltage. Previous researchers have used EHDA to aerosolize proteins with mixed results. This work sets forth a simplified thermodynamic theory and provides recommendations to pharmaceutical companies on how to design more stable protein formulations for aerosol processing or delivery. Finally, a new method of producing liposomes was created. It constructs the liposome one layer at a time. The inside of the liposome is sprayed by EHDA, with the lipid and drug in solution together. As the sprayed monolayer passes through a pool containing a solution of lipid in water, the second part of the bilayer attaches to the inner layer creating a complete bilayer liposome.
An Absorbed-Dose/Dose-Rate Dependence for the Alanine-EPR Dosimetry System and Its Implications in High-Dose Ionizing Radiation Metrology

NIST developed the alanine dosimetry system in the early 1990s to replace radiochromic dye film dosimeters. Later in the decade the alanine system was firmly established as a transfer service for high-dose radiation dosimetry and an integral part of the internal calibration scheme supporting these services. Over the course of the last decade, routine monitoring of the system revealed a small but significant observation that, after examination, led to the characterization of a previously unknown absorbed-dose-dependent, dose-rate effect for the alanine system. Though the potential impact of this effect is anticipated to be extremely limited for NIST’s customer-based transfer dosimetry service, much greater implications may be realized for international measurement comparisons between National Measurement Institutes.
Matrine in association with FD-2 stimulates F508del-cystic fibrosis transmembrane conductance regulator activity in the presence of corrector VX809

Cystic fibrosis is caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and the predominant mutation is termed Phe508del (F508del). Therapy for F508del-CFTR patients is based on the use of Orkambi®, a combination of VX809 and VX770. However, though Orkambi leads to an improvement in the lung function of patients, a progressive reduction in its efficacy has been observed. In order to overcome this effect, the aim of the present study was to investigate the role of matrine and the in-house compound FD-2 in increasing the action of VX809 and VX770. Fischer rat thyroid cells overexpressing F508del-CFTR were treated with matrine, VX809 (corrector) and/or with a number of potentiators (VX770, FD-1 and FD-2). The results demonstrated that matrine was able to stimulate CFTR activity and, in association with FD-2, increased the functionality of the channel in the presence of VX809. Based on these results, it may be hypothesized that FD-2 may be a novel and more effective potentiator compared with VX770.
Regional variations in provenance and abundance of ice-rafted clasts in Arctic Ocean sediments: implications for the configuration of late Quaternary oceanic and atmospheric circulation in the Arctic

The composition and distribution of ice-rafted glacial erratics in late Quaternary sediments define the major current systems of the Arctic Ocean and identify two distinct continental sources for the erratics. In the southern Amerasia basin up to 70% of the erratics are dolostones and limestones (the Amerasia suite) that originated in the carbonate-rich Paleozoic terranes of the Canadian Arctic Islands. These clasts reached the Arctic Ocean in glaciers and were ice-rafted to the core sites in the clockwise Beaufort Gyre. The concentration of erratics decreases northward by 98% along the trend of the gyre from southeastern Canada basin to Makarov basin. The concentration of erratics then triples across the Makarov basin flank of Lomonosov Ridge and siltstone, sandstone and siliceous clasts become dominant in cores from the ridge and the Eurasia basin (the Eurasia suite). The bedrock source for the siltstone and sandstone clasts is uncertain, but bedrock distribution and the distribution of glaciation in northern Eurasia suggest the Taymyr Peninsula-Kara Sea regions. The pattern of clast distribution in the Arctic Ocean sediments and the sharp northward decrease in concentration of clasts of Canadian Arctic Island provenance in the Amerasia basin support the conclusion that the modern circulation pattern of the Arctic Ocean, with the Beaufort Gyre dominant in the Amerasia basin and the Transpolar drift dominant in the Eurasia basin, has controlled both sea-ice and glacial iceberg drift in the Arctic Ocean during interglacial intervals since at least the late Pleistocene. The abruptness of the change in both clast composition and concentration on the Makarov basin flank of Lomonosov Ridge also suggests that the boundary between the Beaufort Gyre and the Transpolar Drift has been relatively stable during interglacials since that time. Because the Beaufort Gyre is wind-driven our data, in conjunction with the westerly directed orientation of sand dunes that formed during the last glacial maximum on the North Slope of Alaska, suggests that atmospheric circulation in the western Arctic during late Quaternary was similar to that of the present. q 2001 Elsevier Science B.V. All rights reserved.
Revisited Role of B Cells in Atherosclerosis

B cells play a crucial role in both humoral and adaptive immune responses and are detectable in murine and human atherosclerotic arteries. Recent findings from mouse models are starting to re-define the complex role(s) of B-cells in the atherosclerosis. We will discuss the involvement of different B-cell subsets in vascular pathology and how B cells could be targeted for therapeutic utility.
Molecular Characterization of the viaB Locus Encoding the Biosynthetic Machinery for Vi Capsule Formation in Salmonella Typhi

The Vi capsular polysaccharide (CPS) of Salmonella enterica serovar Typhi, the cause of human typhoid, is important for infectivity and virulence. The Vi biosynthetic machinery is encoded within the viaB locus composed of 10 genes involved in regulation of expression (tviA), polymer synthesis (tviB-tviE), and cell surface localization of the CPS (vexA-vexE). We cloned the viaB locus from S. Typhi and transposon insertion mutants of individual viaB genes were characterized in Escherichia coli DH5α. Phenotype analysis of viaB mutants revealed that tviB, tviC, tviD and tviE are involved in Vi polymer synthesis. Furthermore, expression of tviB-tviE in E. coli DH5α directed the synthesis of cytoplasmic Vi antigen. Mutants of the ABC transporter genes vexBC and the polysaccharide copolymerase gene vexD accumulated the Vi polymer within the cytoplasm and productivity in these mutants was greatly reduced. In contrast, de novo synthesis of Vi polymer in the export deficient vexA mutant was comparable to wild-type cells, with drastic effects on cell stability. VexE mutant cells exported the Vi, but the CPS was not retained at the cell surface. The secreted polymer of a vexE mutant had different physical characteristics compared to the wild-type Vi.
Elongase Reactions as Control Points in Long-Chain Polyunsaturated Fatty Acid Synthesis

Background Δ6-Desaturase (Fads2) is widely regarded as rate-limiting in the conversion of dietary α-linolenic acid (18:3n-3; ALA) to the long-chain omega-3 polyunsaturated fatty acid docosahexaenoic acid (22:6n-3; DHA). However, increasing dietary ALA or the direct Fads2 product, stearidonic acid (18:4n-3; SDA), increases tissue levels of eicosapentaenoic acid (20:5n-3; EPA) and docosapentaenoic acid (22:5n-3; DPA), but not DHA. These observations suggest that one or more control points must exist beyond ALA metabolism by Fads2. One possible control point is a second reaction involving Fads2 itself, since this enzyme catalyses desaturation of 24:5n-3 to 24:6n-3, as well as ALA to SDA. However, metabolism of EPA and DPA both require elongation reactions. This study examined the activities of two elongase enzymes as well as the second reaction of Fads2 in order to concentrate on the metabolism of EPA to DHA. Methodology/Principal Findings The substrate selectivities, competitive substrate interactions and dose response curves of the rat elongases, Elovl2 and Elovl5 were determined after expression of the enzymes in yeast. The competitive substrate interactions for rat Fads2 were also examined. Rat Elovl2 was active with C20 and C22 polyunsaturated fatty acids and this single enzyme catalysed the sequential elongation reactions of EPA→DPA→24:5n-3. The second reaction DPA→24:5n-3 appeared to be saturated at substrate concentrations not saturating for the first reaction EPA→DPA. ALA dose-dependently inhibited Fads2 conversion of 24:5n-3 to 24:6n-3. Conclusions The competition between ALA and 24:5n-3 for Fads2 may explain the decrease in DHA levels observed after certain intakes of dietary ALA have been exceeded. In addition, the apparent saturation of the second Elovl2 reaction, DPA→24:5n-3, provides further explanations for the accumulation of DPA when ALA, SDA or EPA is provided in the diet. This study suggests that Elovl2 will be critical in understanding if DHA synthesis can be increased by dietary means.
Ridge Regression and Other Kernels for Genomic Selection with R Package rrBLUP

Many important traits in plant breeding are polygenic and therefore recalcitrant to traditional marker‐assisted selection. Genomic selection addresses this complexity by including all markers in the prediction model. A key method for the genomic prediction of breeding values is ridge regression (RR), which is equivalent to best linear unbiased prediction (BLUP) when the genetic covariance between lines is proportional to their similarity in genotype space. This additive model can be broadened to include epistatic effects by using other kernels, such as the Gaussian, which represent inner products in a complex feature space. To facilitate the use of RR and nonadditive kernels in plant breeding, a new software package for R called rrBLUP has been developed. At its core is a fast maximum‐likelihood algorithm for mixed models with a single variance component besides the residual error, which allows for efficient prediction with unreplicated training data. Use of the rrBLUP software is demonstrated through several examples, including the identification of optimal crosses based on superior progeny value. In cross‐validation tests, the prediction accuracy with nonadditive kernels was significantly higher than RR for wheat (Triticum aestivum L.) grain yield but equivalent for several maize (Zea mays L.) traits.