Miracle-dz/UniFAR-FTUs huggingface dataset:
ToxR regulates virulence gene expression in non-O1 strains of Vibrio cholerae that cause epidemic cholera

Vibrio cholerae serogroup O1 has historically been thought to be the exclusive cause of epidemic cholera. O139 is a novel serogroup of V. cholerae which emerged on the Indian subcontinent in the last few months of 1992 and is the first non-O1 serogroup of V. cholerae to cause epidemic cholera. We have investigated the expression of some of the known virulence factors of classical and El Tor O1 strains of V. cholerae in clinical isolates of O139 strains. We show that, in contrast to other non-O1 strains, O139 strains express TcpA, the major subunit of the toxin-coregulated pilus found in O1 strains. As in O1 strains, the expression of cholera toxin and TcpA is coordinately regulated by environmental parameters in O139 strains. Derivatives of O139 strains that contain a toxR null mutation were constructed and used to demonstrate that the expression of cholera toxin, TcpA, and the outer membrane protein OmpU in O139 strains, as in O1 strains, is dependent on ToxR. Two kinds of evidence suggest that O139 strains are closely related to El Tor strains of V. cholerae. First, both O139 and El Tor strains share a restriction fragment length polymorphism for tcpA, which distinguishes El Tor from classical strains of V. cholerae. Second, cholera toxin production in O139 strains is greatly enhanced by culture conditions that have been previously shown to promote production of cholera toxin in El Tor strains and not in classical strains of V. cholerae. Although O139 is a novel serotype of V. cholerae, O139 strains conform to a fundamental theme that has evolved from the study of O1 strains: ToxR mediates coordinate regulation of virulence gene expression.
Aβ Oligomers Cause Localized Ca2+ Elevation, Missorting of Endogenous Tau into Dendrites, Tau Phosphorylation, and Destruction of Microtubules and Spines

Aggregation of amyloid-β (Aβ) and Tau protein are hallmarks of Alzheimer's disease (AD), and according to the Aβ-cascade hypothesis, Aβ is considered toxic for neurons and Tau a downstream target of Aβ. We have investigated differentiated primary hippocampal neurons for early localized changes following exposure to Aβ oligomers. Initial events become evident by missorting of endogenous Tau into the somatodendritic compartment, in contrast to axonal sorting in normal neurons. In missorted dendritic regions there is a depletion of spines and local increase in Ca2+, and breakdown of microtubules. Tau in these regions shows elevated phosphorylation at certain sites diagnostic of AD-Tau (e.g., epitope of antibody 12E8, whose phosphorylation causes detachment of Tau from microtubules, and AT8 epitope), and local elevation of certain kinase activities (e.g., MARK/par-1, BRSK/SADK, p70S6K, cdk5, but not GSK3β, JNK, MAPK). These local effects occur without global changes in Tau, tubulin, or kinase levels. Somatodendritic missorting occurs not only with Tau, but also with other axonal proteins such as neurofilaments, and correlates with pronounced depletion of microtubules and mitochondria. The Aβ-induced effects on microtubule and mitochondria depletion, Tau missorting, and loss of spines are prevented by taxol, indicating that Aβ-induced microtubule destabilization and corresponding traffic defects are key factors in incipient degeneration. By contrast, the rise in Ca2+ levels, kinase activities, and Tau phosphorylation cannot be prevented by taxol. Incipient and local changes similar to those of Aβ oligomers can be evoked by cell stressors (e.g., H2O2, glutamate, serum deprivation), suggesting some common mechanism of signaling.
Imposters: A Study of Pronominal Agreement

Normally, a speaker uses a first person singular pronoun (in English, I, me, mine, myself) to refer to himself or herself. To refer to a single addressee, a speaker uses second person pronouns ( you, yours, yourself). But sometimes third person nonpronominal DPs are used to refer to the speaker--for example, this reporter, yours truly--or to the addressee-- my lord, the baroness, Madam ( Is Madam not feeling well? ). Chris Collins and Paul Postal refer to these DPs as imposters because their third person exterior hides a first or second person core. In this book they study the interactions of imposters with a range of grammatical phenomena, including pronominal agreement, coordinate structures, Principle C phenomena, epithets, fake indexicals, and a property of pronominal agreement they call homogeneity. Collins and Postal conclude that traditional ideas about pronominal features (person, number, gender), which countenance only agreement with an antecedent or the relation of the pronoun to its referent, are much too simple. They sketch elements of a more sophisticated view and argue for its relevance and explanatory power in several data realms. The fundamental proposal of the book is that a pronoun agrees with what they call a source, where its antecedent constitutes only one type of source. They argue that the study of imposters (and closely related camouflage DPs) has far-reaching consequences that are inconsistent with many current theories of anaphora.
Costs associated with complications are lower with capecitabine than with 5‐fluorouracil in patients with colorectal cancer

Capecitabine, an oral alternative to 5‐fluorouracil (5‐FU) in patients with colorectal cancer (CRC), has equal clinical efficacy and a favorable safety profile; however, its use may be limited because of unit cost concerns. In this study, the authors measured the cost of chemotherapy‐related complications during treatment with capecitabine‐ and 5‐FU–based regimens.
Document Context Language Models

Text documents are structured on multiple levels of detail: individual words are related by syntax, but larger units of text are related by discourse structure. Existing language models generally fail to account for discourse structure, but it is crucial if we are to have language models that reward coherence and generate coherent texts. We present and empirically evaluate a set of multi-level recurrent neural network language models, called Document-Context Language Models (DCLM), which incorporate contextual information both within and beyond the sentence. In comparison with word-level recurrent neural network language models, the DCLM models obtain slightly better predictive likelihoods, and considerably better assessments of document coherence.
Multicenter Study of Nucleic Acid Amplification Tests for Detection of Chlamydia trachomatis and Neisseria gonorrhoeae in Children Being Evaluated for Sexual Abuse

Background: Diagnosis of sexually transmitted infections in children suspected of sexual abuse is challenging due to the medico-legal implications of test results. Currently, the forensic standard for diagnosis of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections is culture. In adults, nucleic acid amplification tests (NAATs) are superior to culture for CT, but these tests have been insufficiently evaluated in pediatric populations for forensic purposes. Methods: We evaluated the use of NAATs, using urine and genital swabs versus culture for diagnosis of CT and NG in children evaluated for sexual abuse in 4 US cities. Urine and a genital swab were collected for CT and NG NAATs along with routine cultures. NAAT positives were confirmed by PCR, using an alternate target. Results: Prevalence of infection among 485 female children were 2.7% for CT and 3.3% for NG by NAAT. The sensitivity of urine NAATs for CT and NG relative to vaginal culture was 100%. Eight participants with CT-positive and 4 with NG-positive NAATs had negative culture results (P = 0.018 for CT urine NAATs vs. culture). There were 24 of 485 (4.9%) female participants with a positive NAAT for CT or NG or both versus 16 of 485 (3.3%) with a positive culture for either, resulting in a 33% increase in children with a positive diagnosis. Conclusions: These results suggest that NAATs on urine, with confirmation, are adequate for use as a new forensic standard for diagnosis of CT and NG in children suspected of sexual abuse. Urine NAATs offer a clear advantage over culture in sensitivity and are less invasive than swabs, reducing patient trauma and discomfort.
Not now, maybe later, and often not at all: Situational, institutional, dispositional, epistemological, and technological barriers to business-based online training courses

ROBERTS, LINDA ENDERS. Not Now, Maybe Later, and Often Not at All: Situational, Institutional, Dispositional, Epistemological, and Technological Barriers to Business-Based Online Training Courses. (Under the direction of Paula Berardinelli.) The purpose of the research was to determine whether the situational, institutional, dispositional, epistemological, and technological barriers that affect attrition in distance education apply to the business-based distance training arena. Although reports about distance training students indicate that attrition from distance training is a significant issue, the results from this study find that 90 percent of the business professionals who answered this survey that have taken business-based e-learning courses are not discontinuing their e-learning courses. This finding contradicts many published articles. The free-form comments written by the online learners who answered this survey provided some hints as to what may be keeping these business professionals from abandoning their e-learning courses. The respondents to this study acknowledge that interaction with other learners and with course facilitators, chunking of courses and curricula into appropriate sized pieces, technical support, good course design, and incentives to reach course or curriculum completion have kept them online. NOT NOW, MAYBE LATER, AND OFTEN NOT AT ALL: SITUATIONAL, INSTITUTIONAL, DISPOSITIONAL, EPISTEMOLOGICAL, AND TECHNOLOGICAL BARRIERS TO BUSINESS-BASED ONLINE TRAINING COURSES by LINDA ENDERS ROBERTS A dissertation submitted to the Graduate Faculty of North Carolina State University in partial fulfillment of the requirements for the Degree of Doctor of Education DEPARTMENT OF ADULT AND COMMUNITY COLLEGE EDUCATION
Changes in the presence of multiple markers of circulating melanoma cells correlate with clinical outcome in patients with melanoma.

PURPOSE Melanoma cells can be found in the circulation of patients with melanoma. The following study was conducted to examine whether changes in their presence could provide an early marker of response to therapy. EXPERIMENTAL DESIGN We measured the presence of several markers of melanoma cells in the peripheral blood of 118 patients with resected stage IIb, III, or IV melanoma before and after immunotherapy with a polyvalent, shed antigen, melanoma vaccine using reverse transcription-PCR assays for tyrosinase, gp100, MART-1, and MAGE-3. Assays were conducted at baseline and after 3, 5, and 11 months of therapy. RESULTS Overall, 47% of patients were positive for at least one marker during the study. Before vaccine treatment, circulating melanoma cell markers were present in 23% of patients. After 5 and 7 months of vaccine therapy, the proportion of patients with circulating markers decreased by 27% and 55%, respectively (P for trend = 0.02). The recurrence-free survival of patients whose melanoma cell markers disappeared during vaccine treatment was significantly longer than that of patients in whom they increased, i.e., the percentage of patients who were recurrence free at 1 year was 80% versus 58% (P = 0.03). CONCLUSIONS Therapy with a polyvalent melanoma vaccine was associated with clearance of melanoma cell markers from the circulation, and the clearance was associated with an improved prognosis. These findings suggest that the sequential assay of tumor cells in the circulation by reverse transcription-PCR may provide an early indication of the effectiveness of cancer therapy.
Missed opportunities in child healthcare

Background Various policies in health, such as Integrated Management of Childhood Illnesses, were introduced to enhance integrated service delivery in child healthcare. During clinical practice the researcher observed that integrated services may not be rendered. Objectives This article describes the experiences of mothers that utilised comprehensive child health services in the Cape Metropolitan area of South Africa. Services included treatment for diseases; preventative interventions such as immunisation; and promotive interventions, such as improvement in nutrition and promotion of breastfeeding. Method A qualitative, descriptive phenomenological approach was applied to explore the experiences and perceptions of mothers and/or carers utilising child healthcare services. Thirty percent of the clinics were selected purposively from the total population. A convenience purposive non-probability sampling method was applied to select 17 mothers who met the criteria and gave written consent. Interviews were conducted and recorded digitally using an interview guide. The data analysis was done using Tesch's eight step model. Results Findings of the study indicated varied experiences. Not all mothers received information about the Road to Health book or card. According to the mothers, integrated child healthcare services were not practised. The consequences were missed opportunities in immunisation, provision of vitamin A, absence of growth monitoring, feeding assessment and provision of nutritional advice. Conclusion There is a need for simple interventions such as oral rehydration, early recognition and treatment of diseases, immunisation, growth monitoring and appropriate nutrition advice. These services were not offered diligently. Such interventions could contribute to reducing the incidence of child morbidity and mortality.
A review of the latest clinical compounds to inhibit VEGF in pathological angiogenesis

Angiogenesis plays an important role in the formation of new blood vessels and is crucial for tumour development and progression. Imbalance between pro- and antiangiogenesis factors regulates the biological process of angiogenesis. The best characterised of the proangiogenic factors and the most potent is vascular endothelial growth factor (VEGF). The binding of VEGF to one of its transmembrane tyrosine kinase receptors, which are predominantly found on endothelial cells, results in receptor dimerisation, activation and autophosphorylation of the tyrosine kinase domain. This triggers a cascade of complex downstream signalling pathways. Several strategies targeting the VEGF signalling pathway have been developed. These include neutralising antibodies to VEGF (bevacizumab) or VEGF receptors (VEGFRs) (DC101), soluble VEGFR/VEGFR hybrids (VEGF-Trap), and tyrosine kinase inhibitors of VEGFRs (BAY43-9006, SU11248, ZD6474, AZD2171, PTK/ZK and others). Several of these agents are now being investigated in clinical trials.
Scalar susceptibility in QCD and the multiflavor Schwinger model.

We evaluate the leading infrared behavior of the scalar susceptibility in QCD and in the multiflavor Schwinger model for a small nonzero quark mass {ital m} and/or small nonzero temperature as well as the scalar susceptibility for the finite-volume QCD partition function. In QCD, it is determined by one-loop chiral perturbation theory, with the result that the leading infrared singularity behaves as {approximately}ln{ital m} at zero temperature and as {approximately}{ital T}/{radical}{ital m} at finite temperature. In the Schwinger model with several flavors we use exact results for the scalar correlation function. We find that the Schwinger model has a phase transition at {ital T}=0 with critical exponents that satisfy the standard scaling relations. The singular behavior of this model depends on the number of flavors with a scalar susceptibility that behaves as {approximately}{ital m}{sup {minus}2/({ital N}{sub {ital f}}+1)}. At finite volumes {ital V} we show that the scalar susceptibility is proportional to 1/{ital m}{sup 2}{ital V}. Recent lattice calculations of this quantity by Karsch and Laermann are discussed. {copyright} {ital 1996 The American Physical Society. }
Forced Expression of Myocardin Is Not Sufficient for Induction of Smooth Muscle Differentiation in Multipotential Embryonic Cells

Objective—Myocardin, a coactivator of serum response factor, has been shown to be required for expression of multiple CArG-dependent smooth muscle cell (SMC) marker genes. The aim of the present study was to determine whether myocardin alone is sufficient to induce SMC lineage in multipotential stem cells as evidenced by activation of the entire SMC differentiation program. Methods and Results—Overexpression of myocardin induced only a subset of SMC marker genes, including smooth muscle (SM) α-actin, SM–myosin heavy chain (MHC), SM22α, calponin, and desmin in A404 SMC precursor cells, whereas expression of smoothelin-B, aortic carboxypeptidase-like protein, and focal adhesion kinase-related nonkinase, whose promoters lack efficacious CArG elements, was not induced. Similar results were obtained in cultured SMCs, 10T1/2 cells, and embryonic stem cells. Moreover, myocardin inappropriately induced expression of skeletal and cardiac CArG-dependent genes in cultured SMCs. Stable overexpression of dominant-negative myocardin in A404 cells resulted in impaired induction of SM α-actin and SM–MHC by all trans-retinoic acid but had no effect on induction of smoothelin-B and aortic carboxypeptidase-like protein expression. Conclusions—Taken together with previous studies, results demonstrate that myocardin is required for the induction of CArG-dependent SMC marker genes but is not sufficient to initiate the complete SMC differentiation program.
Automatic Color Enhancement (ACE) and its Fast Implementation

Automatic Color Enhancement “ACE” is an effective method for color image enhancement introduced by Gatta, Rizzi, and Marini based on modeling several low level mechanisms of the human visual system. The direct computation of ACE on an N × N image costs O(N 4 ) operations. This article describes two fast approximations of ACE. First, the algorithm of Bertalm´oo, Caselles, Provenzi, and Rizzi uses a polynomial approximation of the slope function to decomposes the main computation into convolutions, reducing the cost to O(N 2 logN). Second, an algorithm based on interpolating intensity levels also reduces the main computation to convolutions. The use of ACE for image enhancement and color correction is demonstrated.
Common variants spanning PLK4 are associated with mitotic-origin aneuploidy in human embryos

Chromosome number varies in humans Pregnancy loss is often associated with a loss of chromosome number, a condition known as aneuploidy. When examining aneuploid embryos during in vitro fertilization cycles, McCoy et al. found a large genomic region associated with defects in maternal chromosome number (see the Perspective by Vohr and Green). This region contains a gene, Polo-like Kinase 4 (PLK4), that is known to affect chromosome segregation and has variants that correlate with an increased rate of maternal aneuploidy. Surprisingly, such variants occur at relatively high levels in human populations and may be under positive selection. Science, this issue p. 235; see also p. 180 Prenatal genetic screening reveals the candidate gene Polo-like kinase 4, variants of which may affect embryo survival rates. [Also see Perspective by Vohr and Green] Aneuploidy, the inheritance of an atypical chromosome complement, is common in early human development and is the primary cause of pregnancy loss. By screening day-3 embryos during in vitro fertilization cycles, we identified an association between aneuploidy of putative mitotic origin and linked genetic variants on chromosome 4 of maternal genomes. This associated region contains a candidate gene, Polo-like kinase 4 (PLK4), that plays a well-characterized role in centriole duplication and has the ability to alter mitotic fidelity upon minor dysregulation. Mothers with the high-risk genotypes contributed fewer embryos for testing at day 5, suggesting that their embryos are less likely to survive to blastocyst formation. The associated region coincides with a signature of a selective sweep in ancient humans, suggesting that the causal variant was either the target of selection or hitchhiked to substantial frequency.
Escherichia coli O157:H7 Super-Shedder and Non-Shedder Feedlot Steers Harbour Distinct Fecal Bacterial Communities

Escherichia coli O157:H7 is a major foodborne human pathogen causing disease worldwide. Cattle are a major reservoir for this pathogen and those that shed E. coli O157:H7 at >104 CFU/g feces have been termed “super-shedders”. A rich microbial community inhabits the mammalian intestinal tract, but it is not known if the structure of this community differs between super-shedder cattle and their non-shedding pen mates. We hypothesized that the super-shedder state is a result of an intestinal dysbiosis of the microbial community and that a “normal” microbiota prevents E. coli O157:H7 from reaching super-shedding levels. To address this question, we applied 454 pyrosequencing of bacterial 16S rRNA genes to characterize fecal bacterial communities from 11 super-shedders and 11 contemporary pen mates negative for E. coli O157:H7. The dataset was analyzed by using five independent clustering methods to minimize potential biases and to increase confidence in the results. Our analyses collectively indicated significant variations in microbiome composition between super-shedding and non-shedding cattle. Super-shedders exhibited higher bacterial richness and diversity than non-shedders. Furthermore, seventy-two operational taxonomic units, mostly belonging to Firmicutes and Bacteroidetes phyla, were identified showing differential abundance between these two groups of cattle. The operational taxonomic unit affiliation provides new insight into bacterial populations that are present in feces arising from super-shedders of E. coli O157:H7.
The Competitive Cost of Antibiotic Resistance in Mycobacterium tuberculosis

Mathematical models predict that the future of the multidrug-resistant tuberculosis epidemic will depend on the fitness cost of drug resistance. We show that in laboratory-derived mutants of Mycobacterium tuberculosis, rifampin resistance is universally associated with a competitive fitness cost and that this cost is determined by the specific resistance mutation and strain genetic background. In contrast, we demonstrate that prolonged patient treatment can result in multidrug-resistant strains with no fitness defect and that strains with low- or no-cost resistance mutations are also the most frequent among clinical isolates.
Control of the Bone Morphogenetic Protein 7 Gene in Developmental and Adult Life

The TGFβ superfamily growth factor BMP7 performs essential biological functions in embryonic development and regeneration of injured tissue in the adult. BMP7 activity is regulated at numerous levels in the signaling pathway by the expression of extracellular antagonists, decoy receptors and inhibitory cell signaling components. Additionally, expression of the BMP7 gene is tightly controlled both during embryonic development and adult life. In this review, the current status of work on regulation of BMP7 at the genomic level is discussed. In situ hybridization and reporter gene studies have conclusively defined patterns of BMP7 expression in many tissues. Additionally, both in vivo and cell culture studies have defined some of the mechanistic bases for this regulation. In addition to transcriptional activation mediated by binding of activating transcription factors, there is also strong evidence for repression through recruitment of histone modifying enzymes to specific genetic elements. This review summarizes our current understanding of BMP7 gene regulation in embryonic development and adult tissues.