Miracle-dz/UniFAR-FTUs huggingface dataset:
The Sphingomonas Plasmid pCAR3 Is Involved in Complete Mineralization of Carbazole

ABSTRACT We determined the complete 254,797-bp nucleotide sequence of the plasmid pCAR3, a carbazole-degradative plasmid from Sphingomonas sp. strain KA1. A region of about 65 kb involved in replication and conjugative transfer showed similarity to a region of plasmid pNL1 isolated from the aromatic-degrading Novosphingobium aromaticivorans strain F199. The presence of many insertion sequences, transposons, repeat sequences, and their remnants suggest plasticity of this plasmid in genetic structure. Although pCAR3 is thought to carry clustered genes for conjugative transfer, a filter-mating assay between KA1 and a pCAR3-cured strain (KA1W) was unsuccessful, indicating that pCAR3 might be deficient in conjugative transfer. Several degradative genes were found on pCAR3, including two kinds of carbazole-degradative gene clusters (car-I and car-II), and genes for electron transfer components of initial oxygenase for carbazole (fdxI, fdrI, and fdrII). Putative genes were identified for the degradation of anthranilate (and), catechol (cat), 2-hydroxypenta-2,4-dienoate (carDFE), dibenzofuran/fluorene (dbf/fln), protocatechuate (lig), and phthalate (oph). It appears that pCAR3 may carry clustered genes (car-I, car-II, fdxI, fdrI, fdrII, and, and cat) for the degradation of carbazole into tricarboxylic acid cycle intermediates; KA1W completely lost the ability to grow on carbazole, and the carbazole-degradative genes listed above were all expressed when KA1 was grown on carbazole. Reverse transcription-PCR analysis also revealed that the transcription of car-I, car-II, and cat genes was induced by carbazole or its metabolic intermediate. Southern hybridization analyses with probes prepared from car-I, car-II, repA, parA, traI, and traD genes indicated that several Sphingomonas carbazole degraders have DNA regions similar to parts of pCAR3.
Super-polylogarithmic hypergraph coloring hardness via low-degree long codes

We prove improved inapproximability results for hypergraph coloring using the low-degree polynomial code (aka, the"short code" of Barak et. al. [FOCS 2012]) and the techniques proposed by Dinur and Guruswami [FOCS 2013] to incorporate this code for inapproximability results. In particular, we prove quasi-NP-hardness of the following problems on n-vertex hypergraphs: •Coloring a 2-colorable 8-uniform hypergraph with [EQUATION] colors. •Coloring a 4-colorable 4-uniform hypergraph with [EQUATION] colors. •Coloring a 3-colorable 3-uniform hypergraph with [EQUATION] colors. In each of these cases, the hardness results obtained are (at least) superpolynomially stronger (if not exponentially stronger as in the third case) than what was previously known for the respective cases. In fact, prior to this result, (log n)O(1) colors was the strongest quantitative bound on the number of colors ruled out by inapproximability results for O(1)-colorable hypergraphs. The fundamental bottleneck in obtaining coloring inapproximability results using the low-degree long code was a multipartite structural restriction in the PCP construction of Dinur-Guruswami. We are able to get around this restriction by simulating the multipartite structure implicitly by querying just one partition (albeit requiring 8 queries), which yields our result for 2-colorable 8-uniform hypergraphs. The result for 4-colorable 4-uniform hypergraphs is obtained via a "query doubling" method exploiting additional properties of the 8-query test. For 3-colorable 3-uniform hypergraphs, we exploit the ternary domain to design a test with an additive (as opposed to multiplicative) noise function, and analyze its efficacy in killing high weight Fourier coefficients via the pseudorandom properties of an associated quadratic form. The latter step involves extending the key algebraic ingredient of Dinur-Guruswami concerning testing binary Reed-Muller codes to the ternary alphabet.
Cell‐free DNA screening and sex chromosome aneuploidies

Cell‐free DNA (cfDNA) testing is increasingly being used to screen pregnant women for fetal aneuploidies. This technology may also identify fetal sex and can be used to screen for sex chromosome aneuploidies (SCAs). Physicians offering this screening will need to be prepared to offer comprehensive prenatal counseling about these disorders to an increasing number of patients. The purpose of this article is to consider the source of information to use for counseling, factors in parental decision‐making, and the performance characteristics of cfDNA testing in screening for SCAs. Discordance between ultrasound examination and cfDNA results regarding fetal sex is also discussed. © 2015 John Wiley & Sons, Ltd.
Does this patient have Barrett's esophagus? the utility of predicting Barrett's esophagus at the index endoscopy

OBJECTIVES:Few studies have evaluated the ability of the endoscopist to predict the presence of Barrett's esophagus (BE) at index endoscopy. The goals of this study were to determine the operating characteristics of endoscopy in diagnosing BE, and to determine the clinical and endoscopic predictors of BE in suspected BE patients at the index endoscopy.METHODS:From September 1993 to October 1997, endoscopic reports were examined to identify patients with suspected BE. All esophageal pathology reports during the same period were evaluated for the presence of specialized intestinal metaplasia.RESULTS:During the study period, 4053 endoscopies were performed on 2393 patients. Eight percent of all procedures were performed for suspected or confirmed BE. Fifty-three patients were known to have BE and thus their reports were excluded from this analysis. Five hundred seventy of the remaining patients had esophageal biopsies performed, and were included in this analysis. Among these 570 patients, 146 were suspected to have BE on endoscopy, while 424 were not suspected to have BE at the time of endoscopy. There were no differences among the two groups in terms of gender, race, and dyspepsia as an indication for the endoscopy. However, suspected BE patients were slightly younger and were more likely to have heartburn, but were less likely to have dysphagia as an indication for the endoscopy. The sensitivity and specificity of the endoscopists' assessments were 82% (95% confidence interval [CI], 72–92) and 81% (95% CI, 78–84), respectively. The positive predictive value and the negative predictive value were 34% and 97%, respectively. The positive likelihood ratio was 4.32 (95% CI, 3.49–5.31) and the negative likelihood ratio was 0.22 (95% CI, 0.13–0.38). Univariate analysis showed that endoscopists diagnosed BE in those with long-segment BE (LSBE) more accurately than in those with short-segment BE (SSBE) (55% vs 25% p= 0.001; odds ratio [OR] = 3.63, 95% CI, 1.71–7.70). Barrett's esophagus was correctly diagnosed in 38.5% of white patients but in only 14.7% of black patients (p= 0.01; OR = 3.63, 95% CI, 1.31–10.13). Multivariable logistic regression identified only the length of the columnar-appearing segment (p= 0.002; OR = 3.33, 95% CI, 1.54–7.17) and race (p= 0.08; OR = 2.31, 95% CI, 0.88–6.03) to be associated with the presence of BE on biopsy.CONCLUSIONS:Barrett's esophagus is frequently suspected at endoscopy; SSBE was more frequently suspected than LSBE, but was correctly diagnosed only 25% of the time, versus 55% for LSBE. Endoscopists diagnosed BE with a sensitivity of 82% and a specificity of 81%. However, the positive predictive value was only 34%, whereas the negative predictive value was 97%. The length of the columnar-appearing segment is the strongest predictor of BE at endoscopy. Alternative methods are needed to better identify BE patients endoscopically, especially those with SSBE.
Epigenetic inactivation of RASSF1a in uveal melanoma.

PURPOSE The RAS association domain family 1 (RASSF1) gene is a tumor-suppressor gene located on chromosome 3p21.3. The alternative transcript (RASSF1a) has been shown to be inactivated by hypermethylation in several human malignancies, including breast, prostate, and lung cancer, and in cutaneous melanoma. The purpose of this study was to evaluate the methylation status of RASSF1a in human uveal melanoma. METHODS The methylation status of the RASSF1a promoter region was analyzed using PCR in combination with melting curve analysis, sequencing, and restriction enzyme analysis. Eleven human uveal melanoma cell lines, normal melanocytes, 39 archival frozen tumor specimens, and a metastatic lesion of untreated primary uveal melanoma were studied. In addition, whether RASSF1a methylation correlates with patient survival and development of metastatic disease was investigated. RESULTS RASSF1a promoter methylation was detected in 10 of the 11 (91%) cell lines, in 19 of the 38 (50%) patients with primary uveal melanoma and in the metastatic lesion. A positive correlation was found between RASSF1a promoter methylation and development of metastatic disease (P = 0.041). A correlation with disease-free survival could not be established, but a positive trend was observed (P = 0.063). CONCLUSIONS These data show that RASSF1a methylation is a common epigenetic event in uveal melanoma development, potentially of clinical relevance. The presence of a methylated RASSF1a promoter region might therefore serve as a tumor marker and as a possible target for therapeutic intervention.
Challenges of Diagnosing Acute HIV-1 Subtype C Infection in African Women: Performance of a Clinical Algorithm and the Need for Point-of-Care Nucleic-Acid Based Testing

Background Prompt diagnosis of acute HIV infection (AHI) benefits the individual and provides opportunities for public health intervention. The aim of this study was to describe most common signs and symptoms of AHI, correlate these with early disease progression and develop a clinical algorithm to identify acute HIV cases in resource limited setting. Methods 245 South African women at high-risk of HIV-1 were assessed for AHI and received monthly HIV-1 antibody and RNA testing. Signs and symptoms at first HIV-positive visit were compared to HIV-negative visits. Logistic regression identified clinical predictors of AHI. A model-based score was assigned to each predictor to create a risk score for every woman. Results Twenty-eight women seroconverted after a total of 390 person-years of follow-up with an HIV incidence of 7.2/100 person-years (95%CI 4.5–9.8). Fifty-seven percent reported ≥1 sign or symptom at the AHI visit. Factors predictive of AHI included age <25 years (OR = 3.2; 1.4–7.1), rash (OR = 6.1; 2.4–15.4), sore throat (OR = 2.7; 1.0–7.6), weight loss (OR = 4.4; 1.5–13.4), genital ulcers (OR = 8.0; 1.6–39.5) and vaginal discharge (OR = 5.4; 1.6–18.4). A risk score of 2 correctly predicted AHI in 50.0% of cases. The number of signs and symptoms correlated with higher HIV-1 RNA at diagnosis (r = 0.63; p<0.001). Conclusions Accurate recognition of signs and symptoms of AHI is critical for early diagnosis of HIV infection. Our algorithm may assist in risk-stratifying individuals for AHI, especially in resource-limited settings where there is no routine testing for AHI. Independent validation of the algorithm on another cohort is needed to assess its utility further. Point-of-care antigen or viral load technology is required, however, to detect asymptomatic, antibody negative cases enabling early interventions and prevention of transmission.
AMP-Activated Protein Kinase Alpha 2 Deletion Induces VSMC Phenotypic Switching and Reduces Features of Atherosclerotic Plaque Stability.

RATIONALE AMP-activated protein kinase (AMPK) has been reported to play a protective role in atherosclerosis. However, whether AMPKα2 controls atherosclerotic plaque stability remains unknown. OBJECTIVE The aim of this study was to evaluate the impact of AMPKα2 deletion on atherosclerotic plaque stability in advanced atherosclerosis at the brachiocephalic arteries and to elucidate the underlying mechanisms. METHODS AND RESULTS Features of atherosclerotic plaque stability and the markers for contractile or synthetic vascular smooth muscle cell (VSMC) phenotypes were monitored in the brachiocephalic arteries from Apoe(-/-)AMPKα2(-/-) mice or VSMC-specific AMPKα2(-/-) mice in an Apoe(-/-) background (Apoe(-/-)AMPKα2(sm-/-)) fed Western diet for 10 weeks. We identified that Apoe(-/-)AMPKα2(-/-) mice and Apoe(-/-)AMPKα2(sm-/-) mice exhibited similar unstable plaque features, aggravated VSMC phenotypic switching, and significant upregulation of Kruppel-like factor 4 (KLF4) in the plaques located in the brachiocephalic arteries compared with those found in Apoe(-/-) and Apoe(-/-)AMPKα2(sm+/+) control mice. Pravastatin, an AMPK activator, suppressed VSMC phenotypic switching and alleviated features of atherosclerotic plaque instability in Apoe(-/-)AMPKα2(sm+/+) mice, but not in Apoe(-/-)AMPKα2(sm-/-) mice. VSMC isolated from AMPKα2(-/-) mice displayed a significant reduction of contractile proteins(smooth muscle actin-α, calponin, and SM-MHC [smooth muscle-mysion heavy chain]) in parallel with increased detection of synthetic proteins (vimentin and osteopontin) and KLF4, as observed in vivo. KLF4-specific siRNA abolished AMPKα2 deletion-induced VSMC phenotypic switching. Furthermore, pharmacological or genetic inhibition of nuclear factor-κB significantly decreased KLF4 upregulation in VSMC from AMPKα2(-/-) mice. Finally, we found that AMPKα2 deletion markedly promoted the binding of nuclear factor-κBp65 to KLF4 promoter. CONCLUSIONS This study demonstrated that AMPKα2 deletion induces VSMC phenotypic switching and promotes features of atherosclerotic plaque instability in nuclear factor-κB-KLF4-dependent manner.
A Natural Plant-Derived Dihydroisosteviol Prevents Cholera Toxin-Induced Intestinal Fluid Secretion

Stevioside and its major metabolite, steviol, have been reported to affect ion transport in many types of tissues, such as the kidney, pancreas, and intestine. The effect of stevioside, steviol, and its analogs on intestinal Cl- secretion was investigated in a human T84 epithelial cell line. Short-circuit current measurements showed that steviol and analogs isosteviol, dihydroisosteviol, and isosteviol 16-oxime inhibited in a dose-dependent manner forskolin-induced Cl- secretion with IC50 values of 101, 100, 9.6, and 50 μM, respectively, whereas the parent compound stevioside had no effect. Apical Cl- current measurement indicated that dihydroisosteviol targeted the cystic fibrosis transmembrane regulator (CFTR). The inhibitory action of dihydroisosteviol was reversible and was not associated with changes in the intracellular cAMP level. In addition, dihydroisosteviol did not affect calcium-activated chloride secretion and T84 cell viability. In vivo studies using a mouse closed-loop model of cholera toxin-induced intestinal fluid secretion showed that intraluminal injection of 50 μM dihydroisosteviol reduced intestinal fluid secretion by 88.2% without altering fluid absorption. These results indicate that dihydroisosteviol and similar compounds could be a new class of CFTR inhibitors that may be useful for further development as antidiarrheal agents.
CODEX: a next-generation sequencing experiment database for the haematopoietic and embryonic stem cell communities

CODEX (http://codex.stemcells.cam.ac.uk/) is a user-friendly database for the direct access and interrogation of publicly available next-generation sequencing (NGS) data, specifically aimed at experimental biologists. In an era of multi-centre genomic dataset generation, CODEX provides a single database where these samples are collected, uniformly processed and vetted. The main drive of CODEX is to provide the wider scientific community with instant access to high-quality NGS data, which, irrespective of the publishing laboratory, is directly comparable. CODEX allows users to immediately visualize or download processed datasets, or compare user-generated data against the database's cumulative knowledge-base. CODEX contains four types of NGS experiments: transcription factor chromatin immunoprecipitation coupled to high-throughput sequencing (ChIP-Seq), histone modification ChIP-Seq, DNase-Seq and RNA-Seq. These are largely encompassed within two specialized repositories, HAEMCODE and ESCODE, which are focused on haematopoiesis and embryonic stem cell samples, respectively. To date, CODEX contains over 1000 samples, including 221 unique TFs and 93 unique cell types. CODEX therefore provides one of the most complete resources of publicly available NGS data for the direct interrogation of transcriptional programmes that regulate cellular identity and fate in the context of mammalian development, homeostasis and disease.
Phosphorylation of the Retinoblastoma protein (Rb) on serine-807 is required for association with Bax

The recent finding that the Retinoblastoma protein (Rb) is able to regulate apoptosis in a non-transcriptional manner directly at the mitochondria by interaction with the pro-apoptotic protein Bax prompted this investigation of the complex formed between Rb and Bax. Because the function of Rb in the cellular processes of proliferation, apoptosis, senescence and differentiation is regulated by phosphorylation we endeavored to elucidate the phosphorylation status of Rb with respect to its association with Bax and its role in apoptosis. In this study we found that Rb phosphorylated on at least 4 C-terminal phosphorylation sites (S608, S795, S807/S811, and T821) is present at the mitochondria under non-stressed cellular conditions. An in vitro binding assay showed that Bax binds to Rb phosphorylated at S807/S811 in 3 cancer cell types. Physiologically relevant association between Bax and Rb phosphorylated on S807/S811 was demonstrated by reciprocal co-immunoprecipitation experiments using antibodies specific for Rb phosphorylated on S807/S811 and Bax. Mutant Rb proteins expressed in Rb-null C33A cells showed that phosphorylation of S807 of Rb promotes association with Bax and that mimicking phosphorylation at S807 of Rb can block the induction of apoptosis due to PNUTS downregulation. Finally using siRNA to activate phosphatase activity in MCF7 cells, Rb is dephosphorylated at several sites including S807/S811, dissociates from Bax and apoptosis is triggered. These studies show that phosphorylation of Rb regulates its association with Bax and its role in apoptosis.
Multiuser media-based modulation for massive MIMO systems

Media-based modulation (MBM) is an attractive modulation scheme which is getting increased research attention recently. In this paper, we consider MBM for the uplink of a massive MIMO system, which has not been reported before. Each user is equipped with one transmit antenna with multiple radio frequency (RF) mirrors (parasitic elements) placed near it. The base station (BS) is equipped with tens to hundreds of receive antennas. We investigate the potential performance advantage of multiuser MBM (MU-MBM) in a massive MIMO setting. Our results show that multiuser MBM (MU-MBM) can significantly outperform other modulation schemes. For example, a bit error performance achieved using 500 receive antennas at the BS in a massive MIMO system using conventional modulation can be achieved using just 128 antennas using MU-MBM. Even multiuser spatial modulation and generalized spatial modulation in the same massive MIMO settings require more than 200 antennas to achieve the same bit error performance. Also, recognizing that the MU-MBM signal vectors are inherently sparse, we propose an efficient MU-MBM signal detection scheme that uses compressive sensing based reconstruction algorithms like orthogonal matching pursuit (OMP), compressive sampling matching pursuit (CoSaMP), and subspace pursuit (SP).
The luxS Gene of Streptococcus pyogenes Regulates Expression of Genes That Affect Internalization by Epithelial Cells

ABSTRACT The gram-positive pathogen Streptococcus pyogenes was recently reported to possess a homologue of the luxS gene that is responsible for the production of autoinducer 2, which participates in quorum sensing of both gram-positive and gram-negative bacteria. To test the effect of LuxS on streptococcal internalization, a LuxS mutant was constructed in strain SP268, an invasive M3 serotype. Functional analysis of the mutant revealed that it was internalized by HEp-2 cells with higher efficiency than the wild type (wt). Several genes, including hasA (hyaluronic acid synthesis), speB (streptococcal pyrogenic exotoxin B), and csrR (capsule synthesis regulator), a part of a two-component regulatory system, are known to affect the internalization of strain SP268 (J. Jadoun, O. Eyal, and S. Sela, Infect. Immun. 70:462-469, 2002). Therefore, the expression of these genes in the mutant and in the wt was examined. LuxS mutation significantly reduced the mRNA level of speB and increased the mRNA level of emm3. No substantial effect was observed on transcription of hasA and csrR. Yet less hyaluronic acid capsule was expressed in the mutant. Further analysis revealed that luxS is under the regulation of the two-component global regulator CsrR. Our results indicate that LuxS activity in strain SP268 plays an important role in the expression of virulence factors associated with epithelial cell internalization.
Geochemical and Nd isotopic constraints from plutonic rocks on the magmatic and crustal evolution of Southampton Island, Nunavut

Precambrian rocks exposed on Southampton Island, Nunavut, are dominated by plutonic units, consisting mainly of tonalite-granodiorite-monzogranite and minor mafic units. Based on geochemistry, 80 plutonic samples analyzed can be subdivided into 1) a mafic group, 2) a syenite to quartz monzonite group, and 3) a voluminous tonalite to syenogranite group. Compositional gaps and field relationships argue against either a consanguineous or a co-genetic relationship between mafic and felsic compositions. Most samples are metaluminous, magnesian, calcic to calc-alkalic, and exhibit large variations in traceelement concentrations. Thirty regionally distributed Nd isotopic samples yielded T DM ages ranging from 2.79 to 3.65 Ga, indicating a Mesoto Paleoarchean crustal substrate. Strongly negative e Nd (1.9 Ga) values (-4.91 to -19.81) argue against significant material input from depleted mantle sources (e.g. MORB) during Paleoproterozoic granitoid petrogenesis. Regional Nd isotopic data sets plus U-Pb crystallization data sets from these Precambrian rocks support correlation with the diamond-hosting Repulse Bay block of the Rae Province. Résumé : Les roches précambriennes qui affleurent dans l’île Southampton, au Nunavut, sont constituées en prédominance d’unités plutoniques, formées principalement d’unités de tonalite-granodiorite-monzogranite et, dans une moindre mesure, d’unités mafiques. D’après leur composition géochimique, les 80 échantillons plutoniques peuvent être subdivisés en 1) un groupe mafique, 2) un groupe de syénite-monzonite quartzique et 3) un volumineux groupe de tonalite-syénogranite. Les lacunes dans les compositions et les relations observées sur le terrain militent contre un lien consanguin ou cogénétique entre les roches de composition mafique et de composition felsique. La plupart des échantillons sont métalumineux, magnésiens, calciques à calco-alcalins et présentent de grandes variations des concentrations des éléments en traces. Les compositions isotopiques de Nd de 30 échantillons répartis dans la région ont livré des âges modèles (TDM) compris entre 2,79 et 3,65 Ga, ce qui indique un substrat crustal du Mésoarchéen au Paléoarchéen. Des valeurs –Nd (1,9 Ga) fortement négatives (de –4,91 à –19,81) excluent un possible apport significatif de matériaux provenant de sources mantelliques appauvries (p. ex. basalte de dorsale médio-océanique [MORB]) pendant la pétrogenèse des granitoïdes au Paléoprotérozoïque. Des jeux de données de portée régionale sur les compositions isotopiques de Nd ainsi que sur les âges U-Pb de cristallisation soutiennent l’hypothèse d’une corrélation avec le bloc à minéralisation diamantifère de Repulse Bay, de la Province de Rae.