Miracle-dz/UniFAR-FTUs huggingface dataset:
Kaiso mainly locates in the nucleus in vivo and binds to methylated, but not hydroxymethylated DNA.

OBJECTIVE Kaiso is upregulated in many cancers and proposed to bind with both methylated- and unmethylated-DNA in the nucleus as a transcriptional repressor. The objective is to define its subcellular localization in vivo and exact binding DNA sequences in cells. METHODS Compartmentalization of exogenous Kaiso in cells was tracked with enhanced green fluorescence protein (EGFP) tag. The endogenous Kaiso expression in gastric carcinoma tissue was examined with immunohistochemical staining. Kaiso-DNA binding was tested using electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation assay (ChIP). RESULTS Kaiso mainly localized in the nucleus of cancer and stromal cells in vivo, but remained in the cytoplasm of cultured cells. Most importantly, nuclear Kaiso can bind with the methylated-CGCG-containing sequence in the CDKN2A promoter, but not with the hydroxymethylated-CGCG sequence in HCT116 cells. CONCLUSIONS Kaiso locates mainly in the nucleus in vivo where it binds with the methylated-CGCG sequences, but does not bind with the hydroxymethylated-CGCG sequences.
Living near a Major Road in Beijing: Association with Lower Lung Function, Airway Acidification, and Chronic Cough

Background:The effects of near-road pollution on lung function in China have not been well studied. We aimed to investigate the effects of long-term exposure to traffic-related air pollution on lung function, airway inflammation, and respiratory symptoms. Methods:We enrolled 1003 residents aged 57.96 ± 8.99 years living in the Shichahai Community in Beijing. Distances between home addresses and the nearest major roads were measured to calculate home-road distance. We used the distance categories 1, 2, and 3, representing <100 m, 100–200 m, and >200 m, respectively, as the dose indicator for traffic-related air pollution exposure. Lung function, exhaled breath condensate (EBC) pH, and interleukin 6 levels were measured. As a follow-up, 398 participants had a second lung function assessment about 3 years later, and lung function decline was also examined as an outcome. We used regression analysis to assess the impacts of home-road distance on lung function and respiratory symptoms. As the EBC biomarker data were not normally distributed, we performed correlation analysis between home-road distance categories and EBC biomarkers. Results:Participants living a shorter distance from major roads had lower percentage of predicted value of forced expiratory volume in 1 s (FEV1% −1.54, 95% confidence interval [CI]: −0.20 to −2.89). The odds ratio for chronic cough was 2.54 (95% CI: 1.57–4.10) for category 1 and 1.97 (95% CI: 1.16–3.37) for category 2, compared with category 3. EBC pH was positively correlated with road distance (rank correlation coefficient of Spearman [rs] = 0.176, P < 0.001). Conclusions:Long-term exposure to traffic-related air pollution in people who live near major roads in Beijing is associated with lower lung function, airway acidification, and a higher prevalence of chronic cough. EBC pH is a potential useful biomarker for evaluating air pollution exposure.
The online glocal identity of turkish native speakers on Twitter: a focus on age and gender

Today, there are 3.77 billion internet users, 2.80 billion social media users, 4.92 billion mobile users and 2.56 billion mobile social media users worldwide (Kemp, 2017). How can someone differentiate oneself from this huge pack and stand out or do the opposite, show that they belong to a specific community? Without a doubt, the use of language in computer mediated communication (CMC) has an important effect on online self-presentation. When people speak, they do not only exchange information but also give information about themselves and how they relate to the world (Northrup, 2013). Is the way teenagers and middle-aged adults, and women and men use language in social networking sites to project their online global and local identities same or different? This research has attempted to answer these questions for native speakers of Turkish. It is evident that language plays an essential role in online identity presentation in CMC. Prior studies have noted the importance of language in CMC and the electronic revolution (Crystal, 2006)with the information and communication technologies but little importance has been given to the Turkish language in CMC. This study attempts to fill in this gap in literature by analysing Turkish people’s posts in Twitter. English is used as an international and global language and it has become the preferred language of online communication (Rosenhouse & Kowner, 2008). Currently, English is the most commonly taught second language in Turkey (Bayyurt, 2006; 2012) and connects Turkey to the outside world. In this research, the use of English by Turkish native people in CMC explored, with a focus on language contact phenomena. Words taken from English and used in Turkish language are taken as lexical borrowings and English phrases used in Turkish posts are analysed as code-switches. Until now, little importance has been given to the use of English by Turkish people. To our knowledge, this is the first study to examine Turkish people lexical borrowing from English, types of lexical borrowings; cultural and core borrowings, borrowing lexical items; nouns, verbs and other items, code-switching to English, types of code-switching: inter-sentential code-switching and intra-sentential code-switching, and the contents of the posts in which Turkish people prefer using English instead of Turkish with respect to two variables: age and gender.
Clostridium septicum Alpha-Toxin Is Active against the Parasitic Protozoan Toxoplasma gondii and Targets Members of the SAG Family of Glycosylphosphatidylinositol-Anchored Surface Proteins

ABSTRACT As is the case with many other protozoan parasites, glycosylphosphatidylinositol (GPI)-anchored proteins dominate the surface of Toxoplasma gondii tachyzoites. The mechanisms by which T. gondii GPI-anchored proteins are synthesized and transported through the unusual triple-membrane structure of the parasite pellicle to the plasma membrane remain largely unknown. As a first step in developing tools to study these processes, we show here that Clostridium septicum alpha-toxin, a pore-forming toxin that targets GPI-anchored protein receptors on the surface of mammalian cells, is active against T. gondii tachyzoites (50% effective concentration, 0.2 nM). Ultrastructural studies reveal that a tight physical connection between the plasma membrane and the underlying membranes of the inner membrane complex is locally disrupted by toxin treatment, resulting in a massive outward extension of the plasma membrane and ultimately lysis of the parasite. Toxin treatment also causes swelling of the parasite endoplasmic reticulum, providing the first direct evidence that alpha-toxin is a vacuolating toxin. Alpha-toxin binds to several parasite GPI-anchored proteins, including surface antigen 3 (SAG3) and SAG1. Interestingly, differences in the toxin-binding profiles between the virulent RH and avirulent P strain were observed. Alpha-toxin may prove to be a powerful experimental tool for molecular genetic analysis of GPI anchor biosynthesis and GPI-anchored protein trafficking in T. gondii and other susceptible protozoa.
Dietary fiber fraction of germinated barley foodstuff attenuated mucosal damage and diarrhea, and accelerated the repair of the colonic mucosa in an experimental colitis

Background and Aims: Germinated barley foodstuff (GBF) contains protein and insoluble dietary fiber. We have previously shown in ulcerative colitis patients and a colitis model that GBF feeding attenuates mucosal damage by increasing luminal butyrate levels. However, the detailed mechanism remains unclear because of its heterogeneous nature. The present study was carried out to: (i) evaluate the active ingredient in GBF; and (ii) examine its effect on the repair process in colonic inflammation by using a dextran sulfate sodium (DSS) colitis model.
Conservation and variation of nucleotide sequences in Escherichia coli strains isolated from nature

A group of Escherichia coli isolates from nature were compared with one another and with laboratory strains of E. coli with respect to size distribution of chromosomal restriction endonuclease fragments and differences in nucleotide sequences in selected small portions of the genomes. The estimated frequency of base substitutions in nucleotide sequences in and near the trp operons of 26 of the 28 E. coli strains examined ranged from 0.008 to 0.066. Nucleotide sequences in or near lambda prophage homologs were significantly more variable than the sequences in or near trp, tnaA, and thyA genes. Thus, the lambda-homologous regions may have a significant horizontal component in their evolutionary histories, having undergone genetic exchange, whereas the trp, tnaA, and thyA regions may have solely vertical evolutionary histories. The relatedness of the E. coli strains in the genetic regions studied indicated that laboratory strains are not more closely related to one other than they are to isolates from nature. The isolates from natural populations did not form groups related either by host taxa or by geographical region of isolation.
Hypoxia induces a phase transition within a kinase signaling network in cancer cells

Significance Reduced oxygen supply—hypoxia—is a near-universal feature of solid tumors that can alter how tumors respond to therapies. We investigated the transition from normoxia to hypoxia in model brain cancer systems, using single-cell proteomics and data analysis tools based on physicochemical concepts. This approach permits the simplification of otherwise complex biology. We find a hypoxia-induced switch within a mammalian target of rapamycin (mTOR) signaling network. At the switching point, mTOR is predicted, and then shown by experiment, to be unresponsive to inhibition. These results may help explain the undistinguished performance of mTOR inhibitors in certain clinical trials. Hypoxia is a near-universal feature of cancer, promoting glycolysis, cellular proliferation, and angiogenesis. The molecular mechanisms of hypoxic signaling have been intensively studied, but the impact of changes in oxygen partial pressure (pO2) on the state of signaling networks is less clear. In a glioblastoma multiforme (GBM) cancer cell model, we examined the response of signaling networks to targeted pathway inhibition between 21% and 1% pO2. We used a microchip technology that facilitates quantification of a panel of functional proteins from statistical numbers of single cells. We find that near 1.5% pO2, the signaling network associated with mammalian target of rapamycin (mTOR) complex 1 (mTORC1)—a critical component of hypoxic signaling and a compelling cancer drug target—is deregulated in a manner such that it will be unresponsive to mTOR kinase inhibitors near 1.5% pO2, but will respond at higher or lower pO2 values. These predictions were validated through experiments on bulk GBM cell line cultures and on neurosphere cultures of a human-origin GBM xenograft tumor. We attempt to understand this behavior through the use of a quantitative version of Le Chatelier’s principle, as well as through a steady-state kinetic model of protein interactions, both of which indicate that hypoxia can influence mTORC1 signaling as a switch. The Le Chatelier approach also indicates that this switch may be thought of as a type of phase transition. Our analysis indicates that certain biologically complex cell behaviors may be understood using fundamental, thermodynamics-motivated principles.
Responsible entrepreneurship: outlining the contingencies

PurposeThe purpose of this paper is to give an up-to-date assessment of key topics and methods discussed in the current literature on responsible entrepreneurship. In the past years, sustainable development itself has become a more popular and important topic in the academic literature and hence the field of sustainable entrepreneurship has become a greater topic of interest and opportunity for solution. Therefore, a systematic literature review is conducted to assess new contributions to the field and its potential for the future of sustainable development, with a focus on responsible innovation.Design/methodology/approachSystematic, evidence-informed literature review following Tranfieldet al.(2003). FindingsBased on a conceptual literature review, five streams of research that responsible entrepreneurs distinguish from purely for-profit entrepreneurs are identified and discussed: walking the line between profit creation and value creation for society; business models of responsible entrepreneurs; their role in transforming society; getting ready to innovate responsibly; and the role of market incentives to foster sustainable business practices.Originality/valueThe structured literature review allows to identify future research paths. In detail, ideas as regards the management of upcoming tensions when trying to combine profit creation and value creation for society, and finally, the way innovation processes need to be rethought when innovating responsibly are discussed and outlined.
The Molecular Diagnosis of Lymphogranuloma Venereum: Evaluation of a Real-Time Multiplex Polymerase Chain Reaction Test Using Rectal and Urethral Specimens

Objectives: The objectives of this study were to evaluate the use of a real-time multiplex polymerase chain reaction (M-PCR) assay to differentiate between trachoma and lymphogranuloma venereum (LGV) biovars of Chlamydia trachomatis and to validate its performance with the conventional genotyping method. Study: Swab specimens from 115 patients with anorectal symptoms or syndromes associated with LGV were tested by a real-time M-PCR assay and the results compared with the PCR-based restriction fragment length polymorphism analysis of the major outer membrane protein gene (omp1). Results: A high agreement of 96.5% (111 of 115 specimens) was found between the real-time M-PCR testing and the standard genotyping method for the detection of C. trachomatis DNA (&kgr; value, 0.945, P <0.00001). Both methods identified 53 LGV, 32 non-LGV C. trachomatis, and 26 negative specimens. Conclusions: The real-time M-PCR assay simultaneously detects and differentiates LGV from non-LGV strains using swab specimens. This assay offers a relatively rapid and sensitive alternative for the diagnosis of LGV infection and is a useful tool for screening and for outbreak investigations.
Robust importance sampling for efficient SRAM yield analysis

Monte Carlo simulations have been widely adopted for analyzing circuit properties, such as SRAM yield, under strong influence of process variations. Enormous calculation time is required in such a simulation due to the low defect probabilities. In this paper, we propose a robust shift-vector determination for mean-shift importance sampling, by which efficiency and stability of the Monte Carlo simulation is improved. In the proposed method, the hypersphere sampling is developed to autonomously find the optimal shift-vector. The sampling is also limited to the regions where meaningful contribution to the yield is recognized. Simulation examples reveal that the proposed technique stably and efficiently estimates yield of noise stabilities of an SRAM cell. At the failure probability of 10−10, the number of calculation trials has been reduced by six orders magnitude compared with a conventional Monte Carlo simulation.
T Cells from Presensitized Donors Fail to Cause Graft-versus-Host Disease in a Pig-to-Mouse Xenotransplantation Model

Background. The ability of T cells from pigs, the most suitable donors for clinical xenotransplantation, to induce graft-versus-host disease (GVHD) and to facilitate hematopoietic cell engraftment in highly disparate xenogeneic recipients remains unclear. In this article, the authors address these questions in a presensitized pig-to-mouse transplantation model using porcine cytokine-transgenic mice. Methods. Swine donors were presensitized by mouse skin grafting and boosted by the injection of mouse cells after the skin graft was rejected. Porcine peripheral blood mononuclear cells (PBMC) and splenocytes were collected at various times after mouse skin grafting, and their potential to induce GVHD and to facilitate donor hematopoietic cell engraftment in conditioned murine recipients was evaluated. Results. Presensitization of donor pigs resulted in marked enhancement of anti-mouse responses, as reflected in augmented anti-mouse mixed lymphocyte responses, cell-mediated cytotoxicity, and antibody production. However, injection of high numbers of PBMC and splenocytes (>1×108) with bone marrow cells from the presensitized pigs failed to induce detectable GVHD or long-term chimerism in mice that were treated with depleting anti–T-cell and natural killer cell antibodies, cobra venom factor, medronate-liposomes, and 4 Gy of whole-body and 7 Gy of thymic irradiation. Histologic analysis revealed no mononuclear cell infiltration or GVHD-associated lesions in the liver, intestine, lungs, or skin of the mouse recipients. Furthermore, the recipient mice had no detectable T cells or anti-pig immunoglobulin G antibodies in the blood by 6 weeks after injection of porcine cells. Conclusion. These results demonstrate that porcine T-cell function is severely impaired in the xenogeneic murine microenvironment.
Lack of isolate‐specific neutralizing activity is correlated with an increased viral burden in rapidly progressing HIV‐1‐infected patients

ObjectiveTo delineate the interaction between in vivo HIV replication and host antiviral immunity during disease progression in order to elucidate the pathogenesis of AIDS. DesignIn a cohort of HIV-seropositive patients, the serum concentration of viral particles, the blood concentration of mononuclear cells harbouring infectious virus and the serum titre of isolate-specific neutralizing antibodies were correlated with the rates of CD4+ T-cell depletion and disease progression. MethodsUsing a quantitative reverse-transcriptase linked polymerase chain reaction assay, the concentration of viral particles was measured in blood samples from 103 initially symptom-free subjects who were followed up for ≤24 months. The concentration of infectious virus and the neutralizing antibodies to autologous HIV isolates were assessed in 37 out of the 103 subjects. The rate of decrease in CD4 cells over the 24 months was calculated for each subject. ResultsRapidly progressing patients (rate of decrease in CD4 cells ≤60%) had a high concentration of viral particles and a high concentration of infectious virus associated with an undetectable serum titre of isolate-specific neutralizing antibodies. Stable patients (rate of decrease in CD4 cells <30%) had a low concentration of infectious virus and either a low concentration of viral particles with the absence of isolate-specific neutralizing antibodies or a high concentration of viral particles with the presence of isolate-specific neutralizing antibodies. Slowly progressing patients (rate of decrease in CD4 cells ≤30 and <60%) showed an intermediate profile. ConclusionProgression to AIDS is associated with a shift in the balance between viral replication and host immunity that increases the concentration of infected cells and destroys the CD4+ T-lymphocyte population.
Vulnerability Assessment to Climate Variability and Climate Change in Tijuana, Mexico

This paper presents research results of a recent project creating an operational approach to assess vulnerability to climate variability and climate change in Tijuana, Mexico. Despite chronic flooding problems throughout the history of the city, local authorities and state authorities have given little attention to vulnerability to climate variability and climate change. This is the first assessment of vulnerability to flooding carried out in Tijuana. Research results show that over 10 percent of the total population in the city (over 153,000 inhabitants) lives in areas with high vulnerability to flooding, and an additional 18 percent (277,000 inhabitants) are in areas with what we classify as medium-high vulnerability. Results by census track identified specific areas and social groups in these categories, as well as the underlying drivers of vulnerability associated with the biophysical conditions of the landscape that have been modified by urban growth and through social processes (namely, deficiencies in local urban planning and its enforcement along with deficient social policies). Information and knowledge of vulnerability is a useful first step in the long process of creating climate adaptation and resilient pathways within the context of sustainable urban development.
Detecting adaptive trait loci in nonmodel systems: divergence or admixture mapping?

Mapping adaptive trait loci (ATL) underlying ecological divergence is an essential step towards understanding the processes that generate phenotypic diversity. Technological advances have made it possible to sequence exomes in nonmodel systems, providing an efficient means of analysing functional genetic variants. Divergence scans of genetic markers for outlier loci, or ‘divergence mapping’, have been used to map locally adapted genes, but this approach is likely to be underpowered when background divergence is elevated. Genotype–phenotype association tests in admixed populations, or ‘admixture mapping’, may provide a useful approach for mapping locally adapted loci when neutral divergence is high. To determine the power and limits of divergence mapping, we simulated exomes containing a single ATL across two parental populations of varying neutral divergence, estimated divergence and quantified the power to identify the ATL. We found that divergence mapping had very high power when background FST is <0.2, but decreased dramatically above this level. To evaluate the utility of admixture mapping, we simulated exomes from admixed populations, then simulated phenotypes, conducted genotype–phenotype association tests and found that even two generations of random mating after admixture could provide high mapping power in scenarios where pure divergence mapping was ineffective (FST = 0.35). Moreover, admixture mapping had high power across all levels of divergence after 20 generations since admixture. Together with high‐throughput exome sequencing, admixture mapping could be used to map ATL in systems such as Heliconius butterflies or Gryllus crickets when experimental design and analytical approach are chosen accordingly.