Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulation of Serotonin 1B Receptor by Glycogen Synthase Kinase-3

In response to 5-hydroxytryptamine (5-HT), the type 1 serotonin receptors (5-HT1Rs) preferentially couple to the inhibitory G protein and elicit many physiological and behavioral processes. However, their regulation by intracellular protein kinases has not been fully investigated. In this study, we identified that glycogen synthase kinase-3 (GSK3) differentially regulates 5-HT1Rs. In receptor-expressing cells and brain slices, activation of both 5-HT1AR and 5-HT1BR reduced forskolin-stimulated cAMP production, but only the effect of 5-HT1BR was abolished by selective GSK3 inhibitors, deletion of GSK3β by RNAi, or overexpression of impaired GSK3β mutants (R96A and K85,86A). A consensus GSK3 phosphorylation sequence was identified between the serine-154 and threonine-158 in the second intracellular loop of 5-HT1BR. Mutation of either serine-154 or threonine-158 to alanine significantly reduced response of 5-HT1BR to 5-HT. Active GSK3β interacted with resting 5-HT1BR to form a protein complex. The interaction was enhanced by receptor activation, abolished by GSK3 inhibitors, and dependent on the phosphorylation state of serine-154. In addition, regulation of 5-HT1BR by GSK3 changed the dynamics of agonist-induced cell surface receptor internalization, in which lack of phosphorylation at Ser154 resulted in sustained reduction of 5-HT1BR at the cell surface. Although the physiological consequences of selective regulation of 5-HT1BR by GSK3 remain to be identified, findings in this study reveal a new function of GSK3 as a protein kinase that is able to selectively regulate G protein-coupled receptors.
Immediate single tooth replacement with subepithelial connective tissue graft using platform switching implants: a case series.

This case series evaluated the facial gingival stability following single immediate tooth replacement in conjunction with subepithelial connective tissue graft (SCTG). Implant success rate and peri-implant tissue response were also reported. Ten patients (6 male, 4 female), with a mean age of 52.1 (range = 22.7 to 67.1) years, underwent immediate implant placement and provisionalization with SCTG and were evaluated clinically and radiographically at presurgery (T0), at the time of immediate tooth replacement and SCTG (T1), and 3 months (T2), 6 months (T3), and 12 months (T4) after surgery. Data were analyzed using the Friedman and Wilcoxon signed-ranks tests at the significance level of α = . 05. At 1 year, 9 of 10 implants remained osseointegrated with the overall mean marginal bone change of -0.31 mm and a mean facial gingival level change of -0.05 mm. The modified plaque index scores showed that patients were able to maintain a good level of hygiene throughout the study. The papilla index score indicated that at T4, more than 50% of the papilla fill was observed in 89% of all sites. When proper 3-dimensional implant position is achieved and bone graft is placed into the implant-socket gap, favorable success rate and peri-implant tissue response of platform switching implants can be achieved following immediate tooth replacement in conjunction with subepithelial connective tissue graft.
Application of a Tetrazolium Salt with a Water-Soluble Formazan as an Indicator of Viability in Respiring Bacteria

The tetrazolium salt sodium 3′-{1-[(phenylamino)-carbonyl]-3,4-tetrazolium}-bis (4-methoxy-6-nitro)benzene-sulfonic acid hydrate (XTT) was examined for use as a colorimetric indicator of viability in respiring bacteria. XTT was reduced to an orange, water-soluble formazan product by Methylosinus trichosporium OB3b, Pseudomonas putida, Escherichia coli, and Bacillus subtilis. Formazan production was proportional to live cell biomass, and XTT was reduced by all cultures in the absence of added electron-coupling agents. XTT reduction by M. trichosporium OB3b was linear over several hours and was stimulated by the presence of an exogenous substrate (methanol). Addition of cyanide to cultures incubated under oxic conditions gave an initial 10-fold increase in XTT reduction. Viability of bacteria incubated in the absence of exogenous carbon substrates was measured as XTT reduction and compared with viability estimates from plate counts. Results obtained with the two methods were generally comparable, but the XTT assay was superior when cell recovery on plates was low. Incubation of E. coli for 7 days in the absence of exogenous carbon substrates decreased viability by 90%, whereas the corresponding decreases for cultures of M. trichosporium OB3b, P. putida, and B. subtilis were less than 40%.
Fast text detection from single hazy image using smart device

Smart devices have enabled massive improvements in road safety applications. Intelligent camera based driver assistance systems have made driving safe and comfortable. The performance of such systems, however, deteriorates in hazy weather conditions due to poor quality images captured by the smart devices. In this paper, we propose a novel framework for fast detection of text regions in a camera captured single hazy image. A novel text extraction technique using the channels of CMYK color space is used. A simple, fast, and efficient approach of using contrast enhancement technique suitable for smart devices is proposed. A maximum weighted matching based grouping approach is used to form words. We have also created a new dataset of hazy images that contains scene texts and manually annotated the words in it. The framework is implemented in different smart devices to show its efficiency.
Risk Factors for Vertebral and Nonvertebral Fracture Over 10 Years: A Population‐Based Study in Women

Risk factors may vary for different types of fracture, in particular for vertebral fractures. We followed 367 women >50 yr of age from a population‐based cohort for up to 10 yr. Factors that predicted vertebral rather than nonvertebral fractures related to physical weakness, poor health, and weight loss. Similar factors were also associated with greater bone loss at the hip.
Noncytotoxic Suppression of Human Immunodeficiency Virus Type 1 Transcription by Exosomes Secreted from CD8+ T Cells

ABSTRACT CD8+ T cells display a noncytotoxic activity that suppresses transcription of human immunodeficiency virus type 1 (HIV-1) in an antigen-independent and major histocompatibility complex-unrestricted manner. To date, the precise cellular and molecular factors mediating this CD8+ T-cell effector function remain unsolved. Despite evidence indicating the dependence of the activity on cell-cell contact, the possibility of a membrane-mediated activity that represses transcription from the viral promoter remains unexplored. We therefore investigated whether this inhibition of HIV-1 transcription might be elicited by a membrane-bound determinant. Using a CD8+ T-cell line displaying potent noncytotoxic HIV-1 suppression activity, we have identified a membrane-localized HIV-1-suppressing activity that is concomitantly secreted as 30- to 100-nm endosome-derived tetraspanin-rich vesicles known as exosomes. Purified exosomes from CD8+ T-cell culture supernatant noncytotoxically suppressed CCR5-tropic (R5) and CXCR4-tropic (X4) replication of HIV-1 in vitro through a protein moiety. Similar antiviral activity was also found in exosomes isolated from two HIV-1-infected subjects. The antiviral exosomes specifically inhibited HIV-1 transcription in both acute and chronic models of infection. Our results, for the first time, indicate the existence of an antiviral membrane-bound factor consistent with the hallmarks defining noncytotoxic CD8+ T-cell suppression of HIV-1.
Neuronal Dysfunction in iPSC-Derived Medium Spiny Neurons from Chorea-Acanthocytosis Patients Is Reversed by Src Kinase Inhibition and F-Actin Stabilization

Chorea-acanthocytosis (ChAc) is a fatal neurological disorder characterized by red blood cell acanthocytes and striatal neurodegeneration. Recently, severe cell membrane disturbances based on depolymerized cortical actin and an elevated Lyn kinase activity in erythrocytes from ChAc patients were identified. How this contributes to the mechanism of neurodegeneration is still unknown. To gain insight into the pathophysiology, we established a ChAc patient-derived induced pluripotent stem cell model and an efficient differentiation protocol providing a large population of human striatal medium spiny neurons (MSNs), the main target of neurodegeneration in ChAc. Patient-derived MSNs displayed enhanced neurite outgrowth and ramification, whereas synaptic density was similar to controls. Electrophysiological analysis revealed a pathologically elevated synaptic activity in ChAc MSNs. Treatment with the F-actin stabilizer phallacidin or the Src kinase inhibitor PP2 resulted in the significant reduction of disinhibited synaptic currents to healthy control levels, suggesting a Src kinase- and actin-dependent mechanism. This was underlined by increased G/F-actin ratios and elevated Lyn kinase activity in patient-derived MSNs. These data indicate that F-actin stabilization and Src kinase inhibition represent potential therapeutic targets in ChAc that may restore neuronal function. SIGNIFICANCE STATEMENT Chorea-acanthocytosis (ChAc) is a fatal neurodegenerative disease without a known cure. To gain pathophysiological insight, we newly established a human in vitro model using skin biopsies from ChAc patients to generate disease-specific induced pluripotent stem cells (iPSCs) and developed an efficient iPSC differentiation protocol providing striatal medium spiny neurons. Using patch-clamp electrophysiology, we detected a pathologically enhanced synaptic activity in ChAc neurons. Healthy control levels of synaptic activity could be restored by treatment of ChAc neurons with the F-actin stabilizer phallacidin and the Src kinase inhibitor PP2. Because Src kinases are involved in bridging the membrane to the actin cytoskeleton by membrane protein phosphorylation, our data suggest an actin-dependent mechanism of this dysfunctional phenotype and potential treatment targets in ChAc.
Minimum Income and the ‘Working Poor’ Phenomenon

The article discusses the “working poor” phenomenon and issues relating to sociology and labour economics. Firstly, it provides an overview of the poverty assessment. The authors suggest that the methodology used for estimating the poverty level needs to be improved to develop an integrated approach taking into account both the expenditure structure and the household income level. It also analyzes the social and economic aspects of the negative trend that has been significantly high for years. According to the recent data from the Russian national statistical service over forty percent of all Russians with full-time employment still do not earn enough to live with dignity. This is causes the social tension along with purely economic problems such as the reduced consumption, the deficit of household savings, the complicated system of social assistance, the growth of “shadow” economy, the shortage of GDP and the rejection of skilled labour. Finally, it discusses the possibilities to limit the problem. The authors’ study leads to the conclusion that the labour remuneration in market economy empowers employees to escape poverty. It is suggested that the human potential and the working force should be valued and wages should correspond to the labour performance. In particular, the increase in the minimum wage to the level of three subsistence minimums is required ensuring decent standards of
Andrimid producers encode an acetyl-CoA carboxyltransferase subunit resistant to the action of the antibiotic

Andrimid is a hybrid nonribosomal peptide-polyketide antibiotic that blocks the carboxyl-transfer reaction of bacterial acetyl-CoA carboxylase (ACC) and thereby inhibits fatty acid biosynthesis with submicromolar potency. The andrimid biosynthetic gene cluster from Pantoea agglomerans encodes an admT gene with homology to the acetyl-CoA carboxyltransferase (CT) β-subunit gene accD. Escherichia coli cells overexpressing admT showed resistance to andrimid. Co-overproduction of AdmT with E. coli CT α-subunit AccA allowed for the in vitro reconstitution of an active heterologous tetrameric CT A2T2 complex. A subsequent andrimid-inhibition assay revealed an IC50 of 500 nM for this hybrid A2T2 in contrast to that of 12 nM for E. coli CT A2D2. These results validated that AdmT is an AccD homolog that confers resistance in the andrimid producer. Mutagenesis studies guided by the x-ray crystal structure of the E. coli A2D2 complex disclosed a single amino acid mutation of AdmT (L203M) responsible for 5-fold andrimid sensitivity (IC50 = 100 nM). Complementarily, the E. coli AccD mutant M203L became 5-fold more resistant in the CT assays. This observation allowed for bioinformatic identification of several Vibrio cholerae strains in which accD genes encode the Met↔Leu switches, and their occurrences correlate predictively with sensitivities to andrimid in vivo.
Ultrastructure and cell death of in vivo derived and vitrified porcine blastocysts

Morphological and molecular signs of injury and cell death and subsequent regeneration following vitrification of porcine blastocysts were evaluated by light (LM) and transmission electron microscopy (TEM) as well as TUNEL/propidium iodide (PI) nuclear staining followed by confocal microscopy (CSM). In vivo derived blastocysts were assigned to one of the following four groups: Controls—(1) fixed immediately after collection (C0h) and (2) after 24 hr culture in vitro (C24h) and vitrified embryos—(3) fixed immediately after vitrification and warming (V0h), and (4) after 24 hr of culture upon warming after vitrification (V24h). Observation by LM and TEM showed that the V0h embryos displayed collapse of the blastocoele cavity (BC) and cell swelling, a general distension or shrinkage of mitochondria and massive increase in the amount of vesicles, vacuoles, and secondary lysosomes (SLs). Approximately 2/3 of the V24h embryos had recovered, whereas the remaining 1/3 were degenerated. Recovered embryos displayed almost normal blastocyst morphology, except for a widening of the perivitelline space, accumulation of debris and partial distension of mitochondria, whereas degenerated embryos were disintegrated into a poorly defined mass of cells and debris including cells with abundant degeneration of mitochondria and other organelles. Both recovered and degenerated embryos displayed a persistent abundance of presence of small membrane bounded vesicles, vacuoles, and SLs. Evaluation of TUNEL/PI stained embryos showed only occasional appearance of TUNEL positive nuclei with typical apoptotic morphology in controls (C0h 0.67%, C24h 1.22%) and in the V0h embryos (0.93%). The percentage of apoptotic nuclei in embryos at V24h was significantly higher than in all other groups (2.64%). Vitrified embryos showed significantly increased appearance of DNA fragmented nuclei without typical morphological features of apoptosis (V0h 1.43%, V24h 4.30%) compared with controls (C0h 0.26%, C24h 0.45%). The observed morphological changes and increased DNA fragmentation observed immediately after vitrification and warming probably reflects a direct damaging effect of vitrification. During 24 hr of culture a portion of the embryos was able to regenerate and along with the regenerative process, apoptosis—a possible pathway for elimination of damaged cells—became evident. Mol. Reprod. Dev. 70: 155–165, 2005. © 2005 Wiley‐Liss, Inc.
The Border Effects of Domestic Trade in Transitional China: Local Governments’ Preference and Protectionism

Following a two-region border effect model with consumption preference of local governments, this article examines the segmentation of the Chinese domestic market as well as its determinants. Through empirical tests, we find that the average border effect of domestic trade among provinces in China showed an upward trend from 1997–2002 and 2002–2010. The significant difference of border effects between western and eastern areas of China indicate more regional trade barriers in the western areas than in the eastern areas. In addition, compared to agricultural products, there are less trade barriers on industrial products. This partially verifies that there is more trade protection and self-consumption from local government on raw materials. Under the local governments’ preference for regional protection, the higher degree of financial autonomy and larger output share of SOEs will both significantly contribute to the trade barriers among provinces. Local governments’ behavior is the key to understanding the pattern of border effects among provinces.
Signal Restoration Combining Modified Tikhonov Regularization and Preconditioning Technology

The purpose of signal restoration is to acquire a clean signal from the degraded signal which contains blur and noise. In this paper, a modified Tikhonov regularization method based on the standard Tikhonov regularization matrix is proposed, and the corresponding preconditioner is designed to accelerate the convergence of the proposed algorithm. The proposed method shows the best performance than several competitive methods. In addition, the convergence speed is improved significantly.
Prevalence and Predictors of Substance Use

A considerable body of literature has accumulated that examines patterns of substance use and abuse among adolescents attending general education classes. However, much less information exists on the prevalence and predictors of substance use among adolescents with learning disabilities. One purpose of this study was to determine the comparative prevalence of tobacco, alcohol, and marijuana use among a sample of 123 students with learning disabilities (91 male and 32 female, mean age = 14.37 years) and 138 nondisabled students (77 male and 61 female, mean age = 13.71 years). A second purpose was to determine whether two psychosocial variables (self-esteem and type of behavior problem) or severity of drinking problem best predicted use of tobacco and marijuana. Students were administered the Self-Esteem Inventory (SEI)-School form (Coopersmith, 1987) and the Adolescent Drinking Index (ADD (Harrell & Wirtz, 1989); their teachers completed the Revised Behavior Problem Checklist (RBPC) (Quay & Peterson, 1987). Tobacco and marijuana use were proportionally higher for adolescents with learning disabilities; no differences emerged for alcohol use between groups. A discriminant function analysis revealed that scores on the SEI and subscale scores of the RBPC did not reliably predict tobacco or marijuana use for either group. ADI scores were reliable predictors of marijuana use for students with learning disabilities and tobacco use for both groups.
Involvement of a proton‐coupled organic cation antiporter in the blood–brain barrier transport of amantadine

The blood‐to‐brain transport of amantadine, a weak N‐methyl‐d‐aspartate (NMDA) antagonist, has been shown previously to participate in the cationic drug‐sensitive transport system across the mouse blood–brain barrier (BBB). The purpose of the present study was to characterize the influx transport system by means of both an in situ mouse brain perfusion technique and in vitro studies using rat immortalized brain capillary endothelial cells (GPNT). The observed concentration‐dependent initial uptake rate of [3H]amantadine suggested the involvement of a carrier‐mediated transport mechanism. The normal uptake at physiological pH 7.4 was decreased by 72.9% in acidic perfusate, while it was increased by 35.3% in alkaline perfusate. These results suggest that pH‐dependent transport is regulated by utilizing an oppositely directed proton gradient as a driving force. In addition, the [3H]amantadine uptake was moderately inhibited by the adamantane structural analogs (rimantadine and memantine) and other cationic drugs (pyrilamine, clonidine, nicotine, etc.), but not by substrates or inhibitors of the well‐characterized organic cation transporters (tetraethylammonium, l‐carnitine and choline). A similar inhibition pattern was observed between the in vivo studies and the in vitro experiments. These results indicate that the influx transport for amantadine across the BBB involves a proton‐coupled organic cation antiporter. Copyright © 2016 John Wiley & Sons, Ltd.
Thoracolumbar burst frac-tures: the clinical efficacy and outcome of nonoperative management

A storage heater for heating a gaseous heat extraction medium is formed of a container of heat resistant material, preferably metal. At least one guide duct, in the form of a tube for carrying the gaseous heat extraction medium, extends through the container which holds a heat storage medium in the form of a pourable bulk of particulate solid material. The thermal storage medium comprises a bulk in which the product of specific heat of the solid material and the bulk density of the mass is at least 0.7 kcal/ DEG C dm3, the specific heat of the solids material being at least 0.12 kcal/ DEG C kgf and the bulk density of the solids material being at least 2.5 kgf/dm3. The thermal storage medium is a material which can be in direct contact with the air to be heated for places of human habitation.
Making It Spatial Makes It Personal: Engaging Stakeholders with Geospatial Participatory Modeling

Participatory research methods are increasingly used to collectively understand complex social-environmental problems and to design solutions through diverse and inclusive stakeholder engagement. But participatory research rarely engages stakeholders to co-develop and co-interpret models that conceptualize and quantify system dynamics for comparing scenarios of alternate action. Even fewer participatory projects have engaged people using geospatial simulations of dynamic landscape processes and spatially explicit planning scenarios. We contend that geospatial participatory modeling (GPM) can confer multiple benefits over non-spatial approaches for participatory research processes, by (a) personalizing connections to problems and their solutions through visualizations of place, (b) resolving abstract notions of landscape connectivity, and (c) clarifying the spatial scales of drivers, data, and decision-making authority. We illustrate through a case study how GPM is bringing stakeholders together to balance population growth and conservation in a coastal region facing dramatic landscape change due to urbanization and sea level rise. We find that an adaptive, iterative process of model development, sharing, and revision drive innovation of methods and ultimately improve the realism of land change models. This co-production of knowledge enables all participants to fully understand problems, evaluate the acceptability of trade-offs, and build buy-in for management actions in the places where they live and work.