Miracle-dz/UniFAR-FTUs huggingface dataset:
Hypoxia Selectively Disrupts Brain Microvascular Endothelial Tight Junction Complexes Through a Hypoxia‐Inducible Factor‐1 (HIF‐1) Dependent Mechanism

The blood–brain barrier (BBB) constitutes a critical barrier for the maintenance of central nervous system homeostasis. Brain microvascular endothelial cells line the vessel walls and express tight junction (TJ) complexes that restrict paracellular passage across the BBB, thereby fulfilling a crucial role in ensuring brain function. Hypoxia, an impaired O2 delivery, is known to cause BBB dysfunction but the mechanisms that drive this disruption remain unclear. This study discloses the relevance of the master regulator of the hypoxic response, hypoxia‐inducible factor‐1 (HIF‐1), in hypoxia‐induced barrier disruption using the rat brain endothelial cell line RBE4. Hypoxic exposure rapidly induced stabilization of the HIF‐1 oxygen‐dependent alpha subunit (HIF‐1α) concomitantly with BBB impairment and TJ disruption mainly through delocalization and increased tyrosine phosphorylation of TJ proteins. Similar observations were obtained by normoxic stabilization of HIF‐1α using CoCl2, deferoxamine, and dimethyloxalylglycine underlining the involvement of HIF‐1 in barrier dysfunction particularly via TJ alterations. In agreement inhibition of HIF‐1 stabilization by 2‐methoxyestradiol and YC‐1 improved barrier function in hypoxic cells. Overall our data suggests that activation of HIF‐1‐mediated signaling disrupts TJ resulting in increased BBB permeability. J. Cell. Physiol. 229: 1096–1105, 2014. © 2013 Wiley Periodicals, Inc.
Production of the Lantibiotic Salivaricin A and Its Variants by Oral Streptococci and Use of a Specific Induction Assay To Detect Their Presence in Human Saliva

ABSTRACT Salivaricin A (SalA), the first Streptococcus salivarius lantibiotic to be characterized, appears to be inhibitory to most Streptococcus pyogenes strains. A variant of the SalA structural gene (salA1) is present in more than 90% of S. pyogenes strains, but only strains of M serotype 4 and T pattern 4 produce the biologically active peptide. The present study identifies four additional variants (salA2 to salA5) of the SalA structural gene and demonstrates that each of the corresponding inhibitory peptides (SalA2 to SalA5) is produced in vitro. These variants appear to be similar to SalA and SalA1 in their inhibitory activity against Micrococcus luteus and in their ability to act as inducers of SalA production. It had previously been shown that S. pyogenes strain SF370 had a deletion (of approximately 2.5 kb) in the salM and salT genes of the salA1 locus. In the present study, several additional characteristic deletions within the salA1 loci were identified. S. pyogenes strains of the same M serotype all share the same salA1 locus structure. Since S. salivarius is a predominant member of the normal oral flora of healthy humans, strains producing anti-S. pyogenes lantibiotics, such as SalA, may have excellent potential for use as oral probiotics. In the present study, we have used a highly specific SalA induction system to directly detect the presence of SalA in the saliva of humans who either naturally harbor populations of SalA-producing S. salivarius or who have been colonized with the SalA2-producing probiotic S. salivarius K12.
Comparison of five antihypertensive monotherapies and placebo for change in left ventricular mass in patients receiving nutritional-hygienic therapy in the Treatment of Mild Hypertension Study (TOMHS).

BACKGROUND Increased left ventricular mass (LVM) by echocardiography is associated with increased risk of cardiovascular disease. Thus, it is of interest to compare the effects of both pharmacological and nonpharmacological approaches to the treatment of hypertension on reduction of LVM. METHODS AND RESULTS Changes in LV structure were assessed by M-mode echocardiograms in a double-blind, placebo-controlled clinical trial of 844 mild hypertensive participants randomized to nutritional-hygienic (NH) intervention plus placebo or NH plus one of five classes of antihypertensive agents: (1) diuretic (chlorthalidone), (2) beta-blocker (acebutolol), (3) alpha-antagonist (doxazosin mesylate), (4) calcium antagonist (amlodipine maleate), or (5) angiotensin-converting enzyme inhibitor (enalapril maleate). Echocardiograms were performed at baseline, at 3 months, and annually for 4 years. Changes in blood pressure averaged 16/12 mm Hg in the active treatment groups and 9/9 mm Hg in the NH only group. All groups showed significant decreases (10% to 15%) in LVM from baseline that appeared at 3 months and continued for 48 months. The chlorthalidone group experienced the greatest decrease at each follow-up visit (average decrease, 34 g), although the differences from other groups were modest (average decrease among 5 other groups, 24 to 27 g). Participants randomized to NH intervention only had mean changes in LVM similar to those in the participants randomized to NH intervention plus pharmacological treatment. The greatest difference between groups was seen at 12 months, with mean decreases ranging from 35 g (chlorthalidone group) to 17 g (acebutolol group) (P = .001 comparing all groups). Within-group analysis showed that changes in weight, urinary sodium excretion, and systolic BP were moderately correlated with changes in LVM, being statistically significant in most analyses. CONCLUSIONS NH intervention with emphasis on weight loss and reduction of dietary sodium is as effective as NH intervention plus pharmacological treatment in reducing echocardiographically determined LVM, despite a smaller decrease in blood pressure in the NH intervention only group. A possible exception is that the addition of diuretic (chlorthalidone) may have a modest additional effect on reducing LVM.
Remittances inflow and Real Exchange Rate: A Case Study of Pakistan Economy

This paper attempt to investigate the effect of remittances inflow on the real exchange rate over the period of 1980 to 2014 in the context of Pakistan. The main objective of this empirical study is to establish the long run relationship between remittances and real exchange rate, over the period of 1980 to 2014. To examine the long run association between Remittances and real exchange rate in the existence of control variables including Inflation and Terms of Trade (TOT), this study applied ARDL (Autoregressive distributed lag model) an econometric technique for Co-Integration. For the short run relationship between Remittances and Real exchange rate, this study uses ECM (Error Correction Mechanism). The result indicates that remittances inflow causes real exchange rate appreciation. Further, there exist negative relationship between terms of trade and real exchange rate. However, inflation showing positive relationship with real exchange rate.
Sexual dimorphic expression of DMRT1 and Sox9a during gonadal differentiation and hormone‐induced sex reversal in the teleost fish Nile tilapia (Oreochromis niloticus)

We examined the expression profiles of tDMRT1 and Sox9a during gonadal sex differentiation and hormone‐induced sex reversal. tDMRT1 was detected in the gonial germ‐cell–surrounding cells in XY fry specifically before the appearance of any signs of morphological sex differentiation, that is, sex differences in germ cell number and histogenesis, such as differentiation into intratesticular efferent duct or ovarian cavity. The signals became localized in the Sertoli and epithelial cells comprising the efferent duct during gonadal differentiation. After the induction of XY sex reversal with estrogen, tDMRT1 decreased and then disappeared completely. In contrast, tDMRT1 was expressed in the germ‐cell–surrounding cells in XX sex reversal with androgen. On the other hand, Sox9a did not show sexual dimorphism before the appearance of sex differences in histogenesis and was not expressed in the efferent duct in the testis. These results suggest that tDMRT1 is a superior testicular differentiation marker in tilapia. Developmental Dynamics 237:297–306, 2008. © 2007 Wiley‐Liss, Inc.
Price competition with production in advance and inventory carry-over: rst results

A Motivation The two basic oligopoly models of pure quantity competition and pure price competition are known to have a pure strategy equilibrium, which neglects any non-market clearing outcomes. An omniscient auctioneer assigns prices and quantities respectively in a way that there is neither overnor underproduction. The equilibrium of the closely related simultaneous price and quantity competition (PQ game), however, substantially differs from that. For the case of constant marginal cost, Gertner (1986) has derived the functional form of the mixed strategy equilibrium. He has shown that the equilibrium can be completely described by the probability distribution over prices and that firms always produce the full output corresponding to the demand at the price they chose. This equilibrium yields zero expected profits for both firms. From an economic point of view, the PQ game is similar to a price competition with production in advance and perishable goods. The decisive difference to the standard Bertrand game is the fact that the loser has to
Strengthening Parliament's oversight role during international trade negotiations: A grounded theory approach

2 TABLE OF CONTENTS . 4 LIST OF FIGURES . 6 LIST OF TABLES . 7 PLAGIARISM DECLARATION . 8 ACKNOWLEDGMENTS . 9 ABBREVIATIONS AND ACRONYMS . 10
Project control: an exploratory study of levers of control in the context of managing projects

Purpose This paper aims to examine the levers of control (LOC) framework in the context of managing projects. The authors explore the impact of diagnostic systems, interactive systems, beliefs systems and boundary systems on project performance and explore the association between control levers. Design/methodology/approach Using data gathered from 113 project managers representing 38 organizations, the authors used the partial least squares path modelling algorithm to analyse the data. Findings The analysis validates the LOC framework in the context of managing projects and reveals the interrelatedness of control systems and their impact on project performance. Research limitations/implications The conclusions support the current emphasis on performance reporting and change control and highlight the need to consider the interdependencies between control levers. Originality/value This study re-conceptualizes project control by using the LOC framework in the context of managing projects as temporary organizations. This provides a model for investigating and understanding project management control systems that consider the interaction of control mechanisms. Furthermore, the associations between the four control systems and project performance are examined, rather than individual mechanisms in isolation.
Sleep Disturbance During Smoking Cessation: Withdrawal or Side Effect of Treatment?

INTRODUCTION The nicotine-metabolite ratio (NMR) predicts treatment response and is related to treatment side effect severity. Sleep disturbance may be one important side effect, but understanding sleep disturbance effects on smoking cessation is complicated by the fact that nicotine withdrawal also produces sleep disturbance. AIMS To evaluate the effects of withdrawal and treatment side effects on sleep disturbance. METHODS This is a secondary analysis of data from a clinical trial (Lerman et al., 2015) of 1,136 smokers randomised to placebo (n = 363), transdermal nicotine (TN; n = 381), or varenicline (n = 392) and stratified based on NMR (559 slow metabolisers; 577 normal metabolisers). Sleep disturbance was assessed at baseline and at 1-week following the target quit date (TQD). We also examined whether sleep disturbance predicted 7-day point-prevalence abstinence at end-of-treatment (EOT). RESULTS The varenicline and TN groups exhibited greater increases in sleep disturbance (vs. placebo; treatment × time interaction; p = 0.005), particularly among those who quit smoking at 1-week post-TQD. There was a main effect of NMR (p = 0.04), but no interactions with treatment. TN and varenicline attenuated withdrawal symptoms unrelated to sleep (vs. placebo). Greater baseline sleep disturbance predicted relapse at EOT (p = 0.004). CONCLUSIONS Existing treatments may not mitigate withdrawal-related sleep disturbance and adjunctive treatments that target sleep disturbance may improve abstinence rates.
Comparison of two laparoscopic suture patterns for repair of experimentally ruptured urinary bladders in normal neonatal calves.

OBJECTIVE To compare 2 laparoscopic suture patterns for repair of experimentally ruptured urinary bladders in normal neonatal calves. STUDY DESIGN Experimental surgical study. ANIMALS Thirty male Holstein calves. METHODS A bladder defect was created in 24 anesthetized calves (day 0). They were randomly divided into 4 groups (n=6/group). In groups 1 and 3, the defect was closed laparoscopically using a one layer full thickness simple continuous (FTSC) suture pattern (pattern A). In groups 2 and 4, the defect was closed laparoscopically in 2 layers using a FTSC suture pattern followed by Lembert continuous suture pattern (pattern B). Groups 1 and 2 calves were euthanatized at the end of the surgery and groups 3 and 4 at day 10. Six healthy calves were also euthanatized and used as a control group. The bladders were harvested and tested for bursting strength (BS). The surgical time (ST) data from the two groups for each pattern were pooled. A Student t-test was used to compare ST data. For the BS data, a 2-factor ANOVA test with post-hoc Student t-test was used to determine if treatment, time, or treatment-time interaction was significant. A Dunnett's test was used to compare BS of the 4 treatment groups to the control group. P<. 05 was considered significant. RESULTS Mean ST was significantly shorter for pattern A than for pattern B. In all treatment groups, the mean bladder BS (MBBS) was significantly lower than the MBBS for the control group. The MBBS was significantly lower for group 1 than for group 2. There was no significant difference in the MBBS between groups 3 and 4. CONCLUSION In this study, a 1-layer laparoscopic closure technique had advantages compared with 2-layer laparoscopic closure technique. Further work is required before a 1-layer laparoscopic closure technique can be recommended clinically. CLINICAL RELEVANCE One-layer bladder closure is fast and safe in clinically normal calves and permits additional research to evaluate its safety in foals and clinical ruptures.
Energy and Economic Performance Analysis of Heat Recovery Devices Under Different Climate Conditions

High performance buildings typically rely on extreme envelope performances in terms of insulation level, solar gains valorization and airtightness. The energy needs are limited and the system sizing is reduced to facilitate the recourse to renewable energy sources. The only exception to this trend is related to the ventilation and the associated energy needs, which is even more crucial because of the tight infiltration control. Mechanical ventilation is a common option to ensure an appropriate ventilation rate and a suitable indoor air quality. Heat recovery devices are widely used to save energy in buildings mechanical ventilation systems. Their contribution in the design or operating phases is typically assessed in terms of effectiveness, which expresses the ratio between the amount of energy – sensible and/or total – actually recovered and the maximum recoverable under ideal configuration. However, the effectiveness of recovery devices is not a constant value and depends on the operating – outdoor and indoor –conditions and control strategy. In order to evaluate the energy and cost savings allowed by heat recovery systems, these aspects have to be considered, and their relative impact on different heat recovery technologies accounted for. In this work, some of those aspects are analyzed in detail and their contribution to the device effectiveness is discussed. The objective is to understand the influence of the air conditions (fresh and exhaust) on the energy savings considering different sensible and total heat recovery devices and operative constraints which could affect the control strategy. The analysis starts from hourly weather data, representative of different climate types, to quantify the actual effectiveness of different heat recovery systems. The impact of indoor conditions on the sensible and latent recovery is analyzed, defining appropriate control strategies to prevent excessive moisture recovery and discomfort issues when the indoor humidity is considered. Moreover, the effect of condensation and frosting on the hourly and annual performance of each kind of device is analyzed. Three different climatic conditions have been considered. Sensible fixed-plate cross flow heat recovery system has been compared with enthalpy wheels. By means of a parameterization of the operating constraints and the expression of the main quantities in specific terms, depending only on the building use, it has been possible to generalize the main results, making them independent of a specific case study, and to compare different technologies and climatic contexts. Seasonal and annual energy and economic performances have been quantified, providing a synthetic overview of the technical and economic aspects of the considered technologies.
Complementary impact of capabilities and brand orientation on SMBs performance

The purpose of this study is to analyse the interrelationships among capabilities and brand orientation and their effect on performance of the small and medium-sized businesses. A data set of 181 effective responses is collected and Partial Least Squares was used. The main drivers of customer performance are brand orientation and adaptive and brand promotional capabilities, while financial performance is determined by brand promotional and e-marketing capabilities and by customer performance. Brand orientation directly influences adaptive and brand promotional capabilities, while e-marketing capability is positively influenced by brand promotional capability. SMBs operating in the developing economy context need to combine multiple capabilities and brand orientation with focus on building e-marketing capability to improve financial performance. This research study is one of the first in the South-eastern European context to offer evidence-based insights on the structural relations among multiple capabilities, brand orientation and the performance of SMBs.
Gamma‐irradiated quiescent cells repair directly induced double‐strand breaks but accumulate persistent double‐strand breaks during subsequent DNA replication

H2AX is expressed at very low levels in quiescent normal cells in vivo and in vitro. Such cells repair DNA double‐strand breaks (DSBs) induced by γ‐irradiation through a transient stabilization of H2AX. However, the resultant cells accumulate small numbers of irreparable (or persistent) DSBs via an unknown mechanism. We found that quiescent cells that had repaired DSBs directly induced by γ‐rays were prone to accumulate DSBs during the subsequent DNA replication. Unlike directly induced DSBs, secondary DSBs were not efficiently repaired, although Rad51 and 53BP1 were recruited to these sites. H2AX was dramatically stabilized in response to DSBs directly caused by γ‐rays, enabling γH2AX foci formation and DSB repair, whereas H2AX was barely stabilized in response to secondary DSBs, in which γH2AX foci were small and DSBs were not efficiently repaired. Our results show a pathway that leads to the persistent DSB formation after γ‐irradiation.
Dry Powder Nitroimidazopyran Antibiotic PA-824 Aerosol for Inhalation

ABSTRACT We formulated PA-824, a nitroimidazopyran with promise for the treatment of tuberculosis, for efficient aerosol delivery to the lungs in a dry powder porous particle form. The objectives of this study were to prepare and characterize a particulate form of PA-824, assess the stability of this aerosol formulation under different environmental conditions, and determine the pharmacokinetic parameters for the powder after pulmonary administration. The drug was spray dried into porous particles containing a high drug load and possessing desirable aerosol properties for efficient deposition in the lungs. The physical, aerodynamic, and chemical properties of the dry powder were stable at room temperature for 6 months and under refrigerated conditions for at least 1 year. Pharmacokinetic parameters were determined in guinea pigs after the pulmonary administration of the PA-824 powder formulation at three doses (20, 40, and 60 mg/kg of body weight) and compared to those after the intravenous (20 mg/kg) and oral (40 mg/kg) delivery of the drug. Oral and inhaled delivery of PA-824 achieved equivalent systemic delivery at the same body dose within the first 12 h of dosing. However, animals dosed by the pulmonary route showed drug loads that remained locally in the lungs for 32 h postexposure, whereas those given the drug orally cleared the drug more rapidly. Therefore, we expect from these pharmacokinetic data that pulmonary delivery may achieve the same efficacy as oral delivery at the same body dose, with a potential improvement in efficacy related to pulmonary infection. This may translate into the ability to deliver lower body doses of this drug for the treatment of tuberculosis by aerosol.
A two-stage optimization approach for sulphur emission regulation compliance

ABSTRACT In this paper, we present a two-stage optimization model for the machinery system selection problem. The objective is to minimize total cost, while aggregated power requirement and emission regulations are constraining the problem. Future fuel prices are considered to be uncertain. From a set of alternatives, the machinery configuration providing the lowest total cost is found. Also design flexibility in terms of future reconfiguration possibilities is taken into account. The machinery selection for a 2000 TEU container vessel is used as an illustrative case. Five initial machinery concepts are considered: diesel machinery, diesel machinery with a scrubber system, dual fuel (DF) machinery, pure gas engines, and a DF ready machinery. There is also a set of reconfiguration possibilities available for each alternative. From solving the case study, DF machinery is found optimal, while pure gas machinery is close to equally good. By solving the problem with deterministic fuel prices, the value of flexibility is not properly accounted for, resulting in an unreasonably high total cost for the flexible machinery alternatives. This demonstrates the need for a decision support approach that explicitly handles future uncertainty, as the two-stage stochastic model presented in this paper does.