Miracle-dz/UniFAR-FTUs huggingface dataset:
Protective effect of poly(ADP-ribose) synthetase inhibition on multiple organ failure after zymosan-induced peritonitis in the rat.

BACKGROUND AND METHODS In the present study, we tested the hypothesis that peroxynitrite and subsequent activation of the nuclear enzyme poly(ADP-ribose) synthetase (PARS) play a role in the pathogenesis of multiple organ failure induced by peritoneal injection of zymosan in the rat. Animals were randomly divided into six groups (ten rats for each group). The first group was treated with ip administration of saline solution (0.9% NaCl) and served as the sham group. The second group was treated with ip administration of zymosan (500 mg/kg suspended in saline solution). In the third and fourth groups, rats received ip administration of 3-aminobenzamide (10 mg/kg) 1 and 6 hrs after zymosan or saline administration, respectively. In the fifth and sixth groups, rats received ip administration of nicotinamide (50 mg/kg) 1 and 6 hrs after zymosan or saline administration, respectively. After zymosan or saline injection, animals were monitored for 72 hrs to evaluate systemic toxicity (conjunctivitis, ruffled fur, diarrhea, and lethargy), loss of body weight, and mortality. RESULTS A severe inflammatory response, characterized by peritoneal exudation, high plasma and peritoneal levels of nitrate/nitrite (the breakdown products of nitric oxide), and leukocyte infiltration into peritoneal exudate, was induced by zymosan administration. This inflammatory process coincided with the damage of lung, small intestine, and liver as assessed by histologic examination and by an increase of myeloperoxidase activity, which is indicative of neutrophil infiltration. Zymosan-treated rats showed signs of systemic illness, significant loss of body weight, and high mortality rates. Peritoneal administration of zymosan in the rat also induced a significant increase in the plasma levels of peroxynitrite as measured by the oxidation of the fluorescent dihydrorhodamine 123. Immunohistochemical examination demonstrated a marked increase in the immunoreactivity to nitrotyrosine, a specific "footprint" of peroxynitrite, in the lung of zymosan-shocked rats. In vivo treatment with ip administration of 3-aminobenzamide (10 mg/kg, 1 and 6 hrs after zymosan injection) or nicotinamide (50 mg/kg, 1 and 6 hrs after zymosan injection) significantly decreased mortality, inhibited the development of peritonitis, and reduced peroxynitrite formation. In addition, PARS inhibitors were effective in preventing the development of organ failure because tissue injury and neutrophil infiltration, by myeloperoxidase evaluation, were reduced in the lung, small intestine, and liver. CONCLUSIONS In conclusion, the major findings of our study are that peroxynitrite and the consequent PARS activation exert a role in the development of multiple organ failure and that PARS inhibition is an effective anti-inflammatory therapeutic tool.
Defensive Strategy’s Effect on Firm Value: Evidence from Public-Listed Companies in Malaysia

ABSTRACT This study examines the relationship between defensive strategy and firm value for a sample of 596 listed firms in Malaysia over the period 2008 to 2015. For the sake of robustness, the institutional setting is considered in this research by gauging the ownership structure. More specifically, this study seeks to determine whether a firm’s ownership structure might have a significant contribution to the value of its defensive strategy. Additionally, the value creation of defensive strategy is compared among family firms, government-linked firms, and foreign firms. This study concludes that defensive strategy, especially retrenchment strategy, has a positive significance on a firm’s excess value. This implies that defensive strategy will improve the firm performance. The reduction of the costs and assets, the efficiency of monitoring structure, the threat of dismissal, and the promotion of stewardship can enhance a firm’s benefits. Low profitability is found to be better for the firm performance. However, the ownership structures of government-linked and foreign firms tend to have a discount value on the excess value when these firms adopt retrenchment actions. The implication of this study lies in two main points. Firstly, it enriches the body of knowledge by showing how an effective defensive strategy creates value, and the role corporate governance plays in that relationship. Secondly, it helps to inform regulator and policymakers about how defensive strategy might have a good corporate governance to create value.
Combination therapy with venlafaxine and carbamazepine in depressive patients not responding to venlafaxine: pharmacokinetic and clinical aspects

The chiral antidepressant venlafaxine (VEN) is both a serotonin and a norepinephrine uptake inhibitor. CYP2D6 and CYP3A4 contribute to its metabolism, which has been shown to be stereoselective. Ten CYP2D6 genotyped and depressive (F32x and F33x, ICD-10) patients participated in an open study on the pharmacokinetic and pharmacodynamic consequences of a carbamazepine augmentation in VEN non-responders. After an initial 4-week treatment with VEN (195 ± 52 mg/day), the only poor metabolizer out of 10 depressive patients had the highest plasma concentrations of S-VEN and R-VEN, respectively, whereas those of R-O-demethyl-VEN were lowest. Five non-responders completed the second 4-week study period, during which they were submitted to a combined VEN-carbamazepine treatment. In the only non-responder to this combined treatment, there was a dramatic decrease of both enantiomers of VEN, O-demethylvenlafaxine, N-desmethylvenlafaxine and N, O-didesmethylvenlafaxine in plasma, which suggests non-compliance, although metabolic induction by carbamazepine cannot entirely be excluded. The administration of carbamazepine [mean ± SD, range: 360 ± 89 (200-400) mg/day] over 4 weeks did not result in a significant modification of the plasma concentrations of the enantiomers of VEN and its O- and N-demethylated metabolites in the other patients. In conclusion, these preliminary observations suggest that the combination of VEN and carbamazepine represents an interesting augmentation strategy by its efficacy, tolerance and absence of pharmacokinetic modifications. However, these findings should be verified in a more comprehensive study.
Production of epidermal acantholysis in normal human skin in vitro by the IgG fraction from pemphigus serum.

Normal human skin was maintained in organ cultures for several days in Ham's F-10 medium with good preservation of the epidermal cells. When the partially purified IgG fraction from the pooled sera of patients with pemphigus vulgaris or pemphigus foliaceous was added to this culture system, after 24 hr some evidence of epidermal acantholysis was seen. By 72 hr, extensive suprabasilar epidermal acantholysis had occurred in which the acantholytic cells were indistinguishable histologically from the acantholytic cells in biopsies from skin lesions of patients with pemphigus vulgaris. In the control cultures (i.e., F-10 medium or F-10 medium + normal human serum IgG), none of these changes was seen. Direct immunofluorescent staining of these explants using fluorescein-labeled goat antihuman IgG showed that by 6 hr binding of the pemphigus IgG had occurred in the intercellular cement substance of the epidermis. The staining intensity was maximal by 18 to 20 hr. When the pemphigus serum was fractionated by DEAE-cellulose column chromatography, three major IgG-containing peaks (presumably IgG) were eluted which bound to the epidermoid intercellular substance and caused acantholysis in culture. The complement system did not play a role in the antibody-induced acantholysis since complement was not included in this system and heating the reconstituted F-10 + pemphigus IgG for 1 hr at 58 degrees C did not destroy the acantholytic activity. Autoradiographic experiments showed that after about 2 days in culture the rates of incorporation of RNA and protein precursors in the suprabasilar cells in the presence of pemphigus IgG were reduced to less than 10% of the normal IgG controls, whereas these synthetic activities of the basal cells were only slightly affected. These observations lead to the proposal that it is the interaction of the pemphigus autoantibody(s) with the suprabasilar epidermal cell which initiates and possibly substains the process(es) of acantholysis.
Endothelial progenitor dysfunction associates with a type I interferon signature in primary antiphospholipid syndrome

Objectives Patients with antiphospholipid syndrome (APS) are at risk for subclinical endothelial injury, as well as accelerated atherosclerosis. In the related disease systemic lupus erythematosus, there is a well-established defect in circulating endothelial progenitors, which leads to an accrual of endothelial damage over time. This defect has been at least partially attributed to exaggerated expression of type I interferons (IFNs). We sought to determine whether these pathways are important in APS. Methods We studied 68 patients with primary APS. Endothelial progenitors were assessed by flow cytometry and functional assay. Type I IFN activity was determined by a well-accepted bioassay, while peripheral blood mononuclear cells were scored for expression of IFN-responsive genes. Results Endothelial progenitors from patients with APS demonstrated a marked defect in the ability to differentiate into endothelial cells, a phenotype which could be mimicked by treating control progenitors with APS sera. Elevated type I IFN activity was detected in the circulation of patients with APS (a finding that was then replicated in an independent cohort). While IgG depletion from APS sera did not rescue endothelial progenitor function, the dysfunction was successfully reversed by a type I IFN receptor-neutralising antibody. Conclusions We describe, for the first time to our knowledge, an IFN signature in primary APS and show that this promotes impaired endothelial progenitor function. This work opens the door to novel approaches that may mitigate vascular damage in APS, such as anti-IFN drugs.
Relationships between rfb gene clusters required for biosynthesis of identical D-galactose-containing O antigens in Klebsiella pneumoniae serotype O1 and Serratia marcescens serotype O16

The lipopolysaccharide O antigens of Klebsiella pneumoniae serotype O1 and Serratia marcescens serotype O16 both contain a repeating unit disaccharide of [-->3)-beta-D-Galf-(1-->3)-alpha-D-Galp-(1-->]; the resulting polymer is known as D-galactan I. In K. pneumoniae serotype O1, the genes responsible for the synthesis of D-galactan I are found in the rfb gene cluster (rfbKpO1). We report here the cloning and analysis of the rfb cluster from S. marcescens serotype O16 (rfbSmO16). This is the first rfb gene cluster examined for the genus Serratia. Synthesis of D-galactan I is an rfe-dependent process for both K. pneumoniae serotype O1 and S. marcescens serotype O16. Hybridization experiments with probes derived from each of the six rfbKpO1 genes indicate that the cloned rfbSmO16 cluster contains homologous genes arranged in the same order. However, the degree of homology at the nucleotide sequence level was sufficiently low that hybridization was detected only under low-stringency conditions. rfbABSmO16 genes were subcloned and shown to encode an ABC-2 (ATP-binding cassette) transporter which is functionally identical to the one encoded by the corresponding rfb genes from K. pneumoniae serotype O1. The amino acid sequences of the predicted RfbA and RfbB homologs showed identities of 75.7% (87.9% total similarity) and 78.0% (86.5% total similarity), respectively. The last gene of the rfbKpO1 cluster, rfbFKpO1, encodes a bifunctional galactosyltransferase which initiates the formation of D-galactan I. RfbFKpO1 and RfbFSmO16 are 57.6% identical (with 71.1% total similarity), and both show similarity with RfpB, the galactosyltransferase involved in the synthesis of Shigella dysenteriae type I O-polysaccharide. The G+C contents of the rfbAB genes from each organism are quite similar, and values are lower than those typical for the species. However, the G+C content of rfbFSmO16 (47.6%) was much higher than that of rfbFKpO1 (37.3%), despite the fact that the average for each species (52 to 60%) falls within the same range.
In Vivo Anticoagulant and Thrombolytic Activities of a Fibrinolytic Serine Protease (Brevithrombolase) With the k-Carrageenan-Induced Rat Tail Thrombosis Model

In the present study, in vivo thrombolysis efficiency of Brevithrombolase, a nontoxic fibrinolytic enzyme purified from Brevibacillus brevis strain FF02B, was affirmed by significant inhibition of thrombus formation in the k-carrageenan-induced rat tail, in a dose-dependent manner. Brevithrombolase at a dose of 600 µg/kg showed an efficacy that was comparable to streptokinase and plasmin, in dissolving in vivo thrombus of k-carrageenan-treated rats under identical conditions. The in vivo anticoagulant property of Brevithrombolase was demonstrated by its prolongation of activated partial thromboplastin time, prothrombin time, and thrombin time in Wistar rats. However, the Brevithrombolase-treated rats demonstrated an insignificant decrease in fibrinogen (Fg) level of plasma compared with Fg level of control group of rats corroborating in vivo as well as in vitro anticoagulant activity of Brevithrombolase is due to its hydrolytic action on thrombin. These findings unequivocally suggest that Brevithrombolase may serve a promising alternative to the commercial thrombolytic drugs.
Inhibition of Leukocyte Chemotaxis by Factor in Alloxan-Induced Diabetic Rat Plasma

The early local exudative cellular reaction in an inflammatory lesion was impaired in alloxan-induced diabetic rats due to reduced migration of neutrophils to the inflamed area. Neutrophils, however, were capable of moving from reserve compartments into blood in these animals. Furthermore, the functional integrity of their surface membranes, assessed by the capacity of the cells to adhere to nylon fiber, was not altered by alloxan diabetes. An intrinsic cellular defect also did not occur, because the cells were capable of responding to chemotactic stimuli in the Boyden chamber system, provided they were suspended in Eagle's medium or normal serum. Suspended in the corresponding diabetic serum, a blockade of the chemotactic response was observed. Increasing concentrations of diabetic serum, added to a suspension containing neutrophils collected from normal donors, progressively inhibited the response of the cells to a chemotactic stimulus. Hyperglycemia alone or hyperosmolality secondary to hyperglycemia, the presence of ketone bodies, or a direct effect of alloxan did not explain the results. In addition, the capacity to generate chemotactic factors remained intact in diabetic serum. Pretreatment of the diabetic animals with insulin resulted in a gradual recovery of the chemotactic response in vivo and in vitro. We conclude that alloxan-induced diabetic rat serum contains a substance that inhibits neutrophil chemotaxis and that insulin administration is essential for the clearance of this substance from plasma.
Reconstruction of Pharyngolaryngectomy Defects Using the Jejunal Free Flap: A 10-Year Experience from a Single Reconstructive Center

Background: Reconstruction following pharyngolaryngectomy presents a complex reconstructive challenge, and a single-stage, reliable reconstruction allowing prompt discharge from the hospital and return of swallowing and speech function is required. The authors present their 10-year experience of 43 jejunal free flaps for pharyngolaryngectomy reconstruction by a single team and outline their operative algorithm to minimize postoperative morbidity. Methods: The data for patients who underwent jejunal free flap reconstruction of circumferential pharyngoesophageal defects between March of 2000 and September of 2009 were reviewed retrospectively. All cases were included for analysis. Results: There were 31 male patients and 12 female patients, with 100 percent acute flap survival. The authors' overall benign pharyngocutaneous fistula rate was two of 43 (5 percent), with two of 29 (7 percent) occurring in the group without a prophylactic pectoralis muscle flap and zero of 14 occurring in the group that had a prophylactic pectoralis muscle flap. No fistulas occurred when the anastomosis was performed with the gastrointestinal stapler (zero of 48). The authors' overall benign stricture rate was six of 43 (14 percent). Thirty-six patients received either a primary or secondary tracheoesophageal puncture; of these, 28 of 36 (78 percent) used their tracheoesophageal puncture as their primary mode of communication. Conclusion: The authors' recommendations for minimizing fistulas and stricture rate, following free jejunal reconstruction, include the gastrointestinal stapler for bowel anastomosis whenever possible, and the use of a prophylactic pedicled pectoralis major muscle flap for patients exposed to previous radiotherapy.
Determinants of Nominal Effective Exchange Rate in Uganda (2000-2017): A Vecm Approach

This study analyses the main determinants of the nominal effective exchange rate using quarterly time series data covering the period 2000 to 2017. The Augmented Dickey Fuller test confirms that all the with the exception of interest rate were non stationary in levels. This study employs the reduced form Vector Auto-regression (VAR) and Johansen and Juselius cointegration to estimate the long run relationship between exchange rate and other key variables. The VAR is used following the Mundell-Fleming model which argues that, in an open economy with external trade and financial transactions the key macro variables interact and influence each other with lags. The impulse response functions are used to investigate the monetary policy transmission mechanism (MPTM). The study indicates that money supply, terms of trade and inflation were negative while gross domestic product and interest rate were positively related to exchange rate . The variables were found to have a long run relationship. The estimate of the speed of adjustment indicates that when nominal effective exchange rate deviates from the equilibrium, it returns to the equilibrium quickly because of its coefficient of adjustment which is 0.25.
Major Dissociation Between Medial and Lateral Entorhinal Input to Dorsal Hippocampus

Hippocampal place cells are a model system of how the brain constructs cognitive representations and of how these representations support complex behavior, learning, and memory. There is, however, a lack of detailed knowledge about the properties of hippocampal afferents. We recorded multiple single units from the hippocampus and the medial and lateral entorhinal areas of behaving rats. Although many medial entorhinal neurons had highly specific place fields, lateral entorhinal neurons displayed weak spatial specificity. This finding demonstrates a fundamental dissociation between the information conveyed to the hippocampus by its major input streams, with spatial information represented by the medial and nonspatial information represented by the lateral entorhinal cortex.
Pupilla pratensis (Gastropoda: Pupillidae) in the Czech Republic and Slovakia and its distinction from P. muscorum and P. alpicola based on multidimensional analysis of shell measurements

Pupilla pratensis (Clessin, 1871) was recently confirmed as a distinct species based on morphological, ecological and molecular evidence. The main purpose of this study is to publish the first reliable data on the occurrence of P. pratensis in the Czech Republic and Slovakia. The second goal is to analyse conchometry of P. pratensis, P. muscorum (L., 1758), and P. alpicola (Charpentier, 1837) to find out whether it is possible to reliably distinguish these species solely based on shell measurements. For multidimensional analysis of shell measurement variation we used principal components analysis (PCA). We documented six populations of P. pratensis in the Czech Republic and one in SW Slovakia. The revision of voucher material showed that all previously reported records of P. alpicola from the Czech Republic belonged in fact to P. pratensis. This requires the exclusion of P. alpicola from the list of Czech molluscs. Based on multidimensional analysis of shell measurements it was possible to distinguish P. pratensis from P. muscorum with no overlapping specimens. Pupilla alpicola was almost completely different from P. muscorum with only few overlapping specimens, contrary to P. pratensis which was mostly impossible to distinguish from P. alpicola based on analysed shell measurements. Shell width was the best single shell measurement for distinguishing P. pratensis and P. muscorum. Shell measurements of two Swedish populations of P. pratensis did not differ from shell variation of Czech and Slovak populations. However, Scandinavian populations displayed some differences from central European populations in apertural barriers which are discussed in detail. Czech and Slovak populations of P. pratensis occurred in calcium-rich fen meadows which perfectly matches with site characteristics reported from Scandinavia. We assume that the observed morphometric differences between P. pratensis and P. muscorum can be useful for distinguishing the species also outside the Czech territory and for palaeoecological studies where only empty shells are available. Since these species occupy ecologically different habitats their reliable identification in fossil material can improve the reconstructions of past environments.
Transformational leadership for conflict management between leaders and employees

Transformational Leadership for Conflict Management between Leaders and Employees by GUO Yang Master of Philosophy This study empirically investigates the dynamics and outcomes of leader-member conflict. It validates the values of cooperative conflict and damages of competitive conflict between leaders and employees, testing the effectiveness and universality of Deutsch's (1973) cooperation and competition theory. By bridging leadership and conflict management literature, it also identifies the role of transformational leadership in managing conflict effectively. Specifically, transformational leadership induces cooperative conflict and undermines competitive conflict between leaders and employees, which in turn increases task performance and leader effectiveness. A total of 112 interviews were conducted in mainland China from 20 I O to 2011. Results of structural equation modeling and other analyses support the proposed model that transformational leadership affects conflict management approaches ( cooperative conflict management, competitive conflict management) that in turn influence outcomes ( task performance, leader effectiveness). Our findings suggest practical implications that leaders and employees can benefit from well-managed conflict, and that leaders can use transformational values and skills to handle conflict successfully in organizations.