Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of phospholipase D and diacylglycerol in activating constitutive TRPC‐like cation channels in rabbit ear artery myocytes

Previously we have described a constitutively active Ca2+‐permeable non‐selective cation channel in freshly dispersed rabbit ear artery myocytes that has similar properties to canonical transient receptor potential (TRPC) channel proteins. In the present study we have investigated the transduction pathways responsible for stimulating constitutive channel activity in these myocytes. Application of the pharmacological inhibitors of phosphatidylcholine‐phospholipase D (PC‐PLD), butan‐1‐ol and C2 ceramide, produced marked inhibition of constitutive channel activity in cell‐attached patches and also butan‐1‐ol produced pronounced suppression of resting membrane conductance measured with whole‐cell recording whereas the inactive isomer butan‐2‐ol had no effect on constitutive whole‐cell or channel activity. In addition butan‐1‐ol had no effect on channel activity evoked by the diacylglycerol (DAG) analogue 1‐oleoyl‐2‐acetyl‐sn‐glycerol (OAG). Inhibitors of PC‐phospholipase C (PC‐PLC) and phospholipase A2 (PLA2) had no effect on constitutive channel activity. Application of a purified PC‐PLD enzyme and its metabolite phosphatidic acid to inside‐out patches markedly increased channel activity. The phosphatidic acid phosphohydrolase (PAP) inhibitor dl‐propranolol also inhibited constitutive and phosphatidic acid‐induced increases in channel activity but had no effect on OAG‐evoked responses. The DAG lipase and DAG kinase inhibitors, RHC80267 and R59949 respectively, which inhibit DAG metabolism, produced transient increases in channel activity which were mimicked by relatively high concentrations (40 μm) of OAG. The protein kinase C (PKC) inhibitor chelerythrine did not prevent channel activation by OAG but blocked the secondary inhibitory response of OAG. It is proposed that endogenous DAG is involved in the activation of channel activity and that its effects on channel activity are concentration‐dependent with higher concentrations of DAG also inhibiting channel activity through activation of PKC. This study indicates that constitutive cation channel activity in ear artery myocytes is mediated by DAG which is generated by PC‐PLD via phosphatidic acid which represents a novel activation pathway of cation channels in vascular myocytes.
Signaling Cascades Governing Cdc42-Mediated Chondrogenic Differentiation and Mensenchymal Condensation

Endochondral ossification consists of successive steps of chondrocyte differentiation, including mesenchymal condensation, differentiation of chondrocytes, and hypertrophy followed by mineralization and ossification. Loss-of-function studies have revealed that abnormal growth plate cartilage of the Cdc42 mutant contributes to the defects in endochondral bone formation. Here, we have investigated the roles of Cdc42 in osteogenesis and signaling cascades governing Cdc42-mediated chondrogenic differentiation. Though deletion of Cdc42 in limb mesenchymal progenitors led to severe defects in endochondral ossification, either ablation of Cdc42 in limb preosteoblasts or knockdown of Cdc42 in vitro had no obvious effects on bone formation and osteoblast differentiation. However, in Cdc42 mutant limb buds, loss of Cdc42 in mesenchymal progenitors led to marked inactivation of p38 and Smad1/5, and in micromass cultures, Cdc42 lay on the upstream of p38 to activate Smad1/5 in bone morphogenetic protein-2-induced mesenchymal condensation. Finally, Cdc42 also lay on the upstream of protein kinase B to transactivate Sox9 and subsequently induced the expression of chondrocyte differential marker in transforming growth factor-β1-induced chondrogenesis. Taken together, by using biochemical and genetic approaches, we have demonstrated that Cdc42 is involved not in osteogenesis but in chondrogenesis in which the BMP2/Cdc42/Pak/p38/Smad signaling module promotes mesenchymal condensation and the TGF-β/Cdc42/Pak/Akt/Sox9 signaling module facilitates chondrogenic differentiation.
Effects of Selective Serotonin Reuptake Inhibitors (SSRIs) therapy on the female sexual response cycle of women with major depression.

OBJECTIVE Depression and its treatment may influence all aspects of the female sexual function from desire to sexual satisfaction. This study aimed to examine the components of the female sexual response cycle (SRC) of women with major depression treated with Selective Serotonin Reuptake Inhibitors. MATERIALS AND METHODS The correlations structure of the items of the SRC's phases (i.e. desire, arousal, orgasm, satisfaction and pain) in a validated Malay version of Female Sexual Function Index (FSFI) was determined using principal component analysis (PCA), with varimax rotation method. The number of factors obtained was decided using Kaiser's criteria. Factor loadings using PCA with varimax rotation divided the sexual domains into three components based on Kaiser's criteria. RESULTS Sexual desire, sexual arousal, lubrication and orgasm were highly correlated, to form a "sexual drive" construct. Sexual satisfaction and pain made up the second and third components, respectively. SSRIs may affect the components of the SRC causing highly overlapping constructs of sexual drive including orgasm. Recognizing this helps strategizing the treatment approach of female sexual dysfunction in depression particularly in relation to the role of SSRIs.
Cost efficiency of French soccer league teams

This article evaluates the operational activities of French soccer clubs from 2003 to 2011 by using a finite mixture model that allows controlling for unobserved heterogeneity. In doing so, a stochastic frontier latent class model, which allows the existence of different technologies, is adopted to estimate cost frontiers. This procedure not only enables us to identify different groups of French soccer clubs but also permits to analyse their cost efficiency. The main result is that there are two groups among the French soccer clubs, both following completely different ‘technologies’ to obtain league points, suggesting that business strategies need to be adapted to the characteristics of the clubs. Some managerial implications are developed.
A Proposal for Standardization in Forensic Canine DNA Typing: Allele Nomenclature of Six Canine‐Specific STR Loci

ABSTRACT: In this study a proposal for the allele nomenclature of six polymorphic short tandem repeat (STR) loci (PEZ3, PEZ6, PEZ8, PEZ10, FHC2161, and FHC2328) for canine genotyping (Canis lupus familiaris) is presented. The nomenclature is based on the sequence data of the polymorphic region of the microsatellite markers as recommended by the DNA commission of the International Society of Forensic Haemogenetics (ISFH) in 1994 for human DNA typing. To cover commonly and rarely occurring alleles, a selection of homozygous and heterozygous animals were analyzed and subjected to sequence studies. The alleles consisted of simple tri‐ and tetra‐nucleotide repeat patterns as well as compound and highly complex repeat patterns. Several alleles revealing the same fragment size but different repeat structures were found. The allele designation described here was adopted to the number of repeats, including all variable regions within the amplified fragment. In a second step the most commonly occurring alleles were added to an allelic ladder for each marker allowing a reliable typing of all alleles differing in size. A total number of 142 unrelated dogs from surrounding municipal animal homes, private households, and canines in police duty were analyzed. The data were added to a population database providing allele frequencies for each marker.
Towards model-integrated service-oriented manufacturing execution system

The current need for product variation inquires a higher orchestration effort in production to be able to produce at the lowest cost per unit. However, flexibility and low cost per unit are conflicting goals. To deal with this challenge, new types of manufacturing systems have been proposed with the rise of information technologies in the area of discrete manufacturing such as Reconfigurable Manufacturing Systems (RMS). Still, high efforts are necessary to implement configuration changes in such systems, which we aim to overcome with a modular Manufacturing Execution System (MES), where functionalities are grouped as reusable blocks provided by a dedicated library. This position paper presents a conceptual framework for modeling MES in terms of the Systems Modeling Language (SysML). The overall goal is to define a model-integrated MES as generic solution in order to ease reconfiguration efforts. By the term model-integrated we mean that models are not only used for the design of MES but also during operation. In this paper, we evaluate if it is possible to represent MES by SysML with a use case of modeling a demonstrator manufacturing cell, which utilizes OPC UA as communication protocol for machine connection as well as for providing a service-oriented layer as connection point for the MES.
Epstein-Barr virus latent gene expression in uncultured peripheral blood lymphocytes

In this study of Epstein-Barr virus (EBV) latency, the polymerase chain reaction was used in modified form for amplification and detection of viral mRNA sequences in peripheral blood lymphocytes from healthy seropositive adults. Six known promoters for latent gene expression and eight known gene products were identified in in vitro-immortalized lymphocytes and in the cell lines established spontaneously from seropositive adults. We examined whether mRNA expression in uncultured B cells from four seropositive adults was the same as that which occurred in spontaneously established EBV-positive B-cell lines from the same individuals. A minimum of 17 polymerase chain reaction targets was required to circumscribe the known latent mRNA structures. Expression of the C promoter for the EBNA genes was detected in B-cell RNA from three of the four subjects. Transcripts initiated from the alternative W promoter for EBNA expression were not detected. The spliced transcripts detected in the B cells contained only the C2-to-W1 alternative splice, which was nonproductive for EBNA4 gene expression. None of the other EBNA open reading frames were detected spliced onto the 3' ends of the C promoter-initiated RNAs. Spliced RNA from the TP gene was detected in all four subjects. Expression of the TP gene was restricted to TP1 promoter-initiated RNAs, as no TP2 promoter-initiated transcripts were detected. Expression of RNA from the LMP gene was not detected. The F promoter which is active in the restricted expression latency that occurs in Burkitt's lymphoma cells was not detected being expressed in peripheral blood B cells. This pattern of latent gene expression is unique to uncultured B cells, indicating that there are profound differences between viral latent states in vitro and in situ and suggesting a central role for the TP gene in the latency of EBV.
Induction of Apoptosis by Paramyxovirus Simian Virus 5 Lacking a Small Hydrophobic Gene

ABSTRACT Simian virus 5 (SV5) is a member of the paramyxovirus family, which includes emerging viruses such as Hendra virus and Nipah virus as well as many important human and animal pathogens that have been known for years. SV5 encodes eight known viral proteins, including a small hydrophobic integral membrane protein (SH) of 44 amino acids. SV5 without the SH gene (rSV5ΔSH) is viable, and growth of rSV5ΔSH in tissue culture cells and viral protein and mRNA production in rSV5ΔSH-infected cells are indistinguishable from those of the wild-type SV5 virus. However, rSV5ΔSH causes increased cytopathic effect (CPE) and apoptosis in MDBK cells and is attenuated in vivo, suggesting the SH protein plays an important role in SV5 pathogenesis. How rSV5ΔSH induces apoptosis in infected cells has been examined in this report. Tumor necrosis factor alpha (TNF-α), a proinflammatory cytokine, was detected in culture media of rSV5ΔSH-infected cells. Apoptosis induced by rSV5ΔSH was inhibited by neutralizing antibodies against TNF-α and TNF-α receptor 1 (TNF-R1), suggesting that TNF-α played an essential role in rSV5ΔSH-induced apoptosis in a TNF-R1-dependent manner. Examination of important proteins in the TNF-α signaling pathway showed that p65, a major NF-κB subunit whose activation can lead to transcription of TNF-α, was first translocated to the nucleus and was capable of binding to DNA and then was targeted for degradation in rSV5ΔSH-infected cells while expression levels of TNF-R1 remained relatively constant. Thus, rSV5ΔSH induced cell death by activating TNF-α expression, possibly through activation of the NF-κB subunit p65 and then targeting p65 for degradation, leading to apoptosis.
Brain-derived neurotrophic factor Val66met polymorphism and plasma levels in road traffic accident survivors

ABSTRACT Background: Alterations in brain-derived neurotrophic factor (BDNF) expression and release may play a role in the pathogenesis of post-traumatic stress disorder (PTSD). Design: This study evaluated road traffic accident (RTA) survivors to determine whether PTSD and trauma-related factors were associated with plasma BDNF levels and BDNF Val66Met carrier status following RTA exposure. Methods: One hundred and twenty-three RTA survivors (mean age 33.2 years, SD = 10.6 years; 56.9% male) were assessed 10 (SD = 4.9) days after RTA exposure. Acute stress disorder (ASD), as assessed with the Acute Stress Disorder Scale, was present in 50 (42.0%) of the participants. Plasma BDNF levels were measured with enzyme-linked immunosorbent assay and BDNF Val66Met genotyping was performed. PTSD, as assessed with the Clinician-Administered PTSD Scale, was present in 10 (10.8%) participants at 6 months follow-up. Results: Neither BDNF Val66Met genotype nor plasma BDNF was significantly associated with the presence or severity of ASD or PTSD. Plasma BDNF levels were, however, significantly correlated with the lifetime number of trauma exposures. Conclusions: In RTA survivors, plasma BDNF levels increased with increasing number of prior trauma exposures. Plasma BDNF may, therefore, be a marker of trauma load.
ENHANCING PULMONARY DRUG DISPERSION USING LIPID SURFACTANTS IN A MURINE MODEL

Cystic fibrosis is a life-shortening genetic disease that affects the respiratory, digestive and reproductive systems. Though it manifests a variety of symptoms, it is most notably characterized by chronic pulmonary infections that ultimately lead to respiratory failure and premature death. Recent research has focused on developing inhaled aerosol antibiotics to treat such infections; however, current formulations use saline liquid carriers that are unable to fully disperse the drugs throughout the lungs, as the surface tension of saline is much higher than the surface tension of the airway liquid surface. Given that certain lipid surfactants are capable of lowering the surface tension of aqueous solutions, our hypothesis is that a surfactant-based liquid carrier could greatly improve pulmonary drug dispersion and efficacy to better treat lung infections. Previous work both in vitro and in a small group of cystic fibrosis patients has led to the creation of an optimized, selfdispersing inhaled carrier formation that significantly enhances aerosolized drug spreading under very specific, laboratory conditions. The aims of this project are to develop an in vivo imaging model to assess pulmonary drug dispersion, and then to use this model to determine if our surfactant-based formulation also improves drug dispersion in a murine model. To model drug dispersal in the lungs, we instilled BL/6 mice with a combination of fluorescent dye and either water or surfactant, and then measured the amount of fluorescence in different planar regions of the lungs. We then calculated the ratio of fluorescence in the peripheral lung regions to the total
Estimation of exposure time to GSM-900 radiation causing auditory brainstem response changes in rabbits using neuro-fuzzy system

The wide and growing usage of cellular phones has raised questions about the possible health risks associated with radio frequency (RF) electromagnetic fields. Since it is very difficult to accurately measure and quantify the RF exposure level for all individuals, it would be helpful for epidemiologists and cellular phone users to obtain a time estimate of specific radiation exposure generating health problems. In this paper, a neuro-fuzzy system (ANFIS) was developed to estimate GSM-900 radiation exposure time causing specific electrophysiological time-related changes in auditory pathway. The proposed system, exploiting available experimental results for auditory brainstem response changes in rabbits due to mobile phone radiation exposure, resulted in about 90% of correct time recognitions. Thus we have proved, on one hand the short-term effect of mobile phone usage to subjects' auditory pathway, and on the other hand that it is possible to build an automated system detecting satisfactory the radiation exposure time. This system can be very useful, as it provides reliable exposure assessment, even though it is unsafe to extrapolate neurological data from nonhuman in vivo experiments.
A new 3D surface reconstruction method and its application in industrial CT

A fast surface reconstruction algorithm is proposed in this paper for processing large scale industrial CT images with high resolution. Through the following main steps: surface tracking in the single layer, a data caching mechanism and triangle strip generation, the algorithm can extract and represent surfaces efficiently on current mainstream PCs. The experimental results tested in real industrial CT datasets are also reported.
Safety-critical human detection featuring time-of-flight environment perception

Industrie 4.0, Industrial IoT, and cyber-physical production systems in general introduce high levels of automation. Hence, at shop floor level, for example, the interfaces between human and machines are crucial. If a robot's environment perception is not robust and fail-safe, humans may not be detected properly, which may cause critical consequences. However, given the resource constraints of safety controllers typically used in critical application domains, the implementation of complex computer vision algorithms is often challenging. Here we explore the capabilities the indirect Time-of-Flight environment perception technology provides in order to speed up complex computer vision algorithms. In particular we are investigating the use-case of human detection in the domains of critical and resource-constrained applications, such as factory automation and automotive. We demonstrate that preprocessing based on Time-of-Flight 3D data can reduce computation time of typically used computer vision algorithms, such as Viola-Jones, by up to 50%. Furthermore, we showcase a human detection demonstrator case-study implemented on an AURIX processing system that represents a state-of-the-art safety controller. By exploiting the Time-of-Flight technology's depth and amplitude data in a clever way, safety-critical human detection is enabled on the AURIX platform. Compared to competing environment perception technologies, the outlined solution is hardly achievable with structured light or stereo visioning due to the safety controller's resource constraints.
Proteomic analysis of the venom of Heterometrus longimanus (Asian black scorpion)

Venoms have evolved over millions of years into potent cocktails of bioactive peptides and proteins. These compounds can be of great value to the pharmaceutical industry for numerous clinical applications. In this study, a novel proteomic – bioinformatic approach was utilised, where chromatography followed by gel electrophoresis was utilised to separate the venom peptides/proteins of Heterometrus longimanus (Asian black scorpion). Purified peptides were analysed by tandem mass spectrometry, de novo sequenced and then homology matched against known peptides in the Swiss‐Prot protein database. Numerous potentially biologically active peptide matches were discovered, and a simple scoring system applied to putatively assign functions to the peptides. As a validation of this approach, the functional composition of the experimentally derived proteome is similar to that of other scorpions, and contains a potent mix of toxins, antimicrobials and ionic channel inhibitors.
Bone marrow mesenchymal stromal cells with support of bispecific antibody and ultrasound-mediated microbubbles prevent myocardial fibrosis via the signal transducer and activators of transcription signaling pathway.

BACKGROUND AIMS This study was initiated to investigate the efficacy of myocardial fibrosis intervention via signal transducer and activators of transcription (STAT) signaling using bone marrow (BM) mesenchymal stromal cells (MSC) with the aid of bispecific antibody (BiAb) and ultrasound-mediated microbubbles (MB). METHODS BiAb (anti-CD29 × anti-myosin light chain antibody; AMLCA) was prepared and combined with isolated MSC from male mice and transfused into female mice with isoproterenol-induced myocardial fibrosis via the tail vein, followed by MB (MSC + BiAb + MB). This study included seven groups: MSC + BiAb + MB; MSC; BiAb; MB; MSC + BiAb; untreated; and control. Five weeks after treatment, expression levels of the sex-determining region of Y-chromosome (SRY), matrix metalloproteinases (MMP)-9, tissue inhibitor of metalloproteinase (TIMP)-1 and vascular endothelial growth factor (VEGF) in myocardium were detected by fluorescent quantitative real-time polymerase chain reaction (qRT-PCR). Collagen distribution was observed using Sirius Red staining. The protein expression of signal transducer and activators of transcription (STAT)1 and STAT3 was detected by Western blot. RESULTS The highest homing number of MSC was in the MSC + BiAb + MB group, second highest in the MSC + BiAb group, and lowest in MSC alone. Compared with the untreated group, MSC + BiAb + MB, MSC + BiAb and MSC groups had decreased levels of MMP-9, TIMP-1, STAT1 and collagen deposition, and increased levels of STAT3. Upregulated STAT3 and downregulated TIMP-1 were significantly different in MSC + BiAb + MB compared with MSC alone or MSC + BiAb. CONCLUSIONS The homing rate and repairing efficacy of MSC improved with treatment utilizing a combination of BiAb and MB. MSC can improve MMP-TIMP expression in injured myocardium and interfere with myocardial fibrosis after homing, a mechanism that may be related to the STAT-mediated signaling pathway.
Foreign Direct Investment in Developed Economies: A Comparison between European and non - European Countries

We analyse the determinants of foreign direct investment (FDI) by multinational corporations (MNCs) in developed economies. We compare between EU and non-EU countries, in the context of an estimated equation derived from economic theory, which compares the main demand and supply-side determinants of FDI. We contribute to the literature in three ways. First, by employing different proxies for demand and supply-side factors. Second, by comparing between European and non-European developed countries. Third, by testing for the relative importance of total factor productivity (TFP) as a determinant of FDI. Our results are in line with theoretical predictions, but point to the importance of TFP as the determinant par excellence of FDI in developed countries. They also highlight differences even within developed European and non-European counties.