Miracle-dz/UniFAR-FTUs huggingface dataset:
Identi fi cation of Variant-Speci fi c Functions of PIK 3 CA by Rapid Phenotyping of Rare Mutations

Large-scale sequencing efforts are uncovering the complexity of cancer genomes, which are composed of causal "driver" mutations that promote tumor progression along with many more pathologically neutral "passenger" events. The majority of mutations, both in known cancer drivers and uncharacterized genes, are generally of low occurrence, highlighting the need to functionally annotate the long tail of infrequent mutations present in heterogeneous cancers. Here we describe a mutation assessment pipeline enabled by high-throughput engineering of molecularly barcoded gene variant expression clones identified by tumor sequencing. We first used this platform to functionally assess tail mutations observed in PIK3CA, which encodes the catalytic subunit alpha of the phosphatidylinositol-4,5-bisphosphate 3kinase (PI3K) frequentlymutated in cancer.Orthogonal screening forPIK3CA variant activity using in vitro and in vivo cell growth and transformation assays differentiated driver from passenger mutations, revealing that PIK3CA variant activity correlates imperfectly with its mutation frequency across breast cancer populations. Although PIK3CA mutations with frequencies above 5% were significantly more oncogenic than wild-type in all assays, mutations occurring at 0.07% to5.0% included thosewith andwithout oncogenic activities that ranged fromweak to strong in at least one assay. Proteomic profiling coupled with therapeutic sensitivity assays on PIK3CA variant-expressing cell models revealed variantspecific activation of PI3K signaling as well as other pathways that include the MEK1/2 module of mitogen-activated protein kinase pathway. Our data indicate that cancer treatments will need to increasingly consider the functional relevance of specific mutations in driver genes rather than considering all mutations in drivers as equivalent. Cancer Res; 75(24); 5341–54. 2015 AACR.
Physiological Roles of Two Dissimilatory Nitrate Reductases in the Deep-Sea Denitrifier Pseudomonas sp. Strain MT-1

The deep-sea denitrifier Pseudomonas sp. strain MT-1 has two distinct gene clusters encoding dissimilatory nitrate reductases, periplasmic nitrate reductase (Nap) and membrane-bound nitrate reductase (Nar). In order to investigate the physiological roles of these enzymes, we determined the nitrate reductase activity of the soluble and membrane fractions from MT-1 and the type strain of Pseudomonas stutzeri (closely related with MT-1) grown under various conditions. In MT-1, the activities of both fractions were highest when the cells were grown anaerobically in the presence of nitrate under atmospheric pressure. However, the activity of the soluble fraction decreased when the cells were grown under high pressure, whereas that of membrane fraction remained constant. Further, the activity of the soluble fraction decreased when the enzyme reaction was performed at low temperature, although that of membrane fraction was not similarly affected. Additionally, the results of RT-PCR showed that expression of the nar genes was strongly induced under high pressure. In contrast, P. stutzeri T showed no such response following a shift in growth pressure. These results suggest that MT-1 possesses a special mechanism for adaptation to the low-temperature and high-pressure environments of the deep sea, and that Nar is the main dissimilatory nitrate reductase in MT-1 in such environments.
New PCR Assay Using Glucose-6-Phosphate Dehydrogenase for Identification of Leishmania Species

ABSTRACT Glucose-6-phosphate dehydrogenase (G6PD) is one of the multilocus enzymes used to identify Leishmania by zymodeme analysis. The polymorphic pattern revealed by partial characterization of the gene encoding G6PD generated molecular markers useful in the identification of different Leishmania species by PCR. Initially degenerate oligonucleotides were designed on the basis of data on the conserved active center described for other organisms. Primers for reverse transcription-PCR experiments, designed from the nucleotide sequence of the PCR product, enabled us to characterize the 5′ and 3′ untranslated regions and the G6PD open reading frame of reference strains of Leishmania (Viannia) braziliensis, Leishmania (Viannia) guyanensis, Leishmania (Leishmania) mexicana, and Leishmania (Leishmania) amazonensis. Sets of paired primers were designed and used in PCR assays to discriminate between the parasites responsible for tegumentar leishmaniasis of the subgenera Leishmania (Leishmania) and Leishmania (Viannia) and to distinguish L. (Viannia) braziliensis from others organisms of the subgenus Leishmania (Viannia). No amplification products were detected for the DNA of Crithidia fasciculata, Trypanosoma cruzi, or Leishmania (Sauroleishmania) tarentolae or DNA from a healthy human control. The tests proved to be specific and were sensitive enough to detect parasites in human biopsy specimens. The successful discrimination of L. (Viannia) braziliensis from other parasites of the subgenus Leishmania (Viannia) opens the way to epidemiological studies in areas where more than one species of the subgenus Leishmania (Viannia) exist, such as Amazonia, as well as follow-up studies after chemotherapy and assessment of clinical prognoses.
Rosiglitazone improves exercise capacity in individuals with type 2 diabetes.

OBJECTIVE Although exercise is recommended as a cornerstone of treatment for type 2 diabetes, it is often poorly adopted by patients. We have noted that even in the absence of apparent cardiovascular disease, persons with type 2 diabetes have an impaired ability to carry out maximal exercise, and the impairment is correlated with insulin resistance and endothelial dysfunction. We hypothesized that administration of a thiazolidinedione (TZD) agent would improve exercise capacity in type 2 diabetes. RESEARCH DESIGN AND METHODS Twenty participants with uncomplicated type 2 diabetes were randomly assigned in a double-blind study to receive either 4 mg/day of rosiglitazone or matching placebo after baseline measurements to assess endothelial function (brachial artery diameter by brachial ultrasound), maximal oxygen consumption (VO(2max)), oxygen uptake (VO(2)) kinetics, and insulin sensitivity by hyperinsulinemic-euglycemic clamp. Measurements were reassessed after 4 months of treatment. RESULTS Participant groups did not differ at baseline in any measure. Rosiglitazone-treated participants (n = 10) had significantly improved VO(2max) (19.8 +/- 5.3 ml . kg(-1) . min(-1) before rosiglitazone vs. 21.2 +/- 5.1 ml . kg(-1) . min(-1) after rosiglitazone, P < 0.01), insulin sensitivity, and endothelial function. A change in VO(2max) correlated with improved insulin sensitivity measured by clamp (r = 0.68, P < 0.05) and with improved brachial artery diameter (r = 0.70, P < 0.05). Placebo-treated participants (n = 10) showed no changes in VO(2max) (19.4 +/- 5.2 ml . kg(-1) . min(-1) before rosiglitazone vs. 18.1 +/- 5.3 ml . kg(-1) . min(-1) after rosiglitazone, NS) or brachial artery diameter. CONCLUSIONS This is the first known report showing that a TZD improved exercise function in type 2 diabetes. Whether this is due to the observed improvements in insulin sensitivity and/or endothelial function or to another action of the TZD class requires further exploration.
Global distribution and climate forcing of marine organic aerosol – Part 2: Effects on cloud properties and radiative forcing

A series of simulations with the Community At- mosphere Model version 5 (CAM5) with a 7-mode Modal Aerosol Model were conducted to assess the changes in cloud microphysical properties and radiative forcing result- ing from marine organic aerosols. Model simulations show that the anthropogenic aerosol indirect forcing (AIF) pre- dicted by CAM5 is decreased in absolute magnitude by up to 0.09 W m 2 (7 %) when marine organic aerosols are in- cluded. Changes in the AIF from marine organic aerosols are associated with small global increases in low-level in- cloud droplet number concentration and liquid water path of 1.3 cm 3 (1.5 %) and 0.22 g m 2 (0.5 %), respectively. Areas especially sensitive to changes in cloud properties due to ma- rine organic aerosol include the Southern Ocean, North Pa- cific Ocean, and North Atlantic Ocean, all of which are char- acterized by high marine organic emission rates. As climate models are particularly sensitive to the background aerosol concentration, this small but non-negligible change in the AIF due to marine organic aerosols provides a notable link for ocean-ecosystem marine low-level cloud interactions and may be a candidate for consideration in future earth system models.
Salmeterol: a four week study of a long-acting beta-adrenoceptor agonist for the treatment of reversible airways disease.

A total of 1,068 patients, aged 18-70 yrs, with mild to moderate reversible airways disease, were recruited into a multicentre, double-blind, parallel group study in 76 European centres. Following a 2 week run-in period, the 692 patients fulfilling the entry criteria were randomized to 4 weeks treatment with either salmeterol 12.5, 50 or 100 micrograms or placebo b.d. all given by pressurized inhaler, with assessments of symptoms and ventilatory lung function prior to dosing. All three doses of salmeterol had significant efficacy, manifested by increased morning and evening peak expiratory flow rate (PEFR) (by 35-59 l.min-1 and 11-38 l.min-1, respectively), by reduced diurnal variation in PEFR, and by reduced requirement for additional bronchodilator for symptomatic relief. These effects were dose-related. Daytime asthma symptoms and nocturnal awakenings were significantly reduced by salmeterol treatment, although these reductions were not dose-related. The incidence of adverse events was low. Pharmacologically predictable events (e.g. tremor) were more frequent after treatment with 100 micrograms b.d. than with placebo. On the basis of the efficacy and side-effect information, 50 micrograms b.d. is considered to be the optimum dose for the treatment of this group of asthmatics.
A randomised controlled trial comparing transnasal humidified rapid insufflation ventilatory exchange (THRIVE) pre‐oxygenation with facemask pre‐oxygenation in patients undergoing rapid sequence induction of anaesthesia

Pre‐oxygenation is an essential part of rapid sequence induction of general anaesthesia for emergency surgery, in order to increase the oxygen reservoir in the lungs. We performed a randomised controlled trial of transnasal humidified rapid insufflation ventilatory exchange (THRIVE) pre‐oxygenation or facemask pre‐oxygenation in patients undergoing emergency surgery. Twenty patients were allocated to each group. No patient developed arterial oxygen saturation < 90% during attempted tracheal intubation. Arterial blood gases were sampled from an arterial catheter immediately after intubation. The mean (SD) PaO2 was 43.7 (15.2) kPa in the THRIVE group vs. 41.9 (16.2) kPa in the facemask group (p = 0.722); PaCO2 was 5.8 (1.1) kPa in the THRIVE group vs. 5.6 (1.0) kPa in the facemask group (p = 0.631); arterial pH was 7.36 (0.05) in the THRIVE group vs. 7.34 (0.06) in the facemask group (p = 0.447). No airway rescue manoeuvres were needed, and there were no differences in the number of laryngoscopy attempts between the groups. In spite of this, patients in the THRIVE group had a significantly longer apnoea time of 248 (71) s compared with 123 (55) s in the facemask group (p < 0.001). Transnasal humidified rapid insufflation ventilatory exchange is a practicable method for pre‐oxygenating patients during rapid sequence induction of general anaesthesia for emergency surgery; we found that it maintained an equivalent blood gas profile to facemask pre‐oxygenation, in spite of a significantly longer apnoea time.
Classical description of spin wave excitation by currents in bulk ferromagnets

A modification of the Landau-Lifshitz equation accounts for the effect of the current on the magnetization in the "slow passage" limit, according to which the spins precess about the exchange field quickly in comparison to the rate of change of the orientation of the magnetization as seen in the reference frame of the conduction electrons. This model implies that the spin polarization of the current provokes an instability of the magnetization in the bulk of a ferromagnet when the current density reaches a threshold.
Population analysis of CD4+ T cell chemokine receptor transcript expression during in vivo type‐1 (mycobacterial) and type‐2 (schistosomal) immune responses

Chemokine receptor transcripts were defined among CD4+ T cells in lymph nodes of mice with type‐1 and type‐2 inflammation, respectively, elicited by mycobacterial and schistosomal Ag. CXCR3 and CCR6 transcripts were biased to type‐1, and CCR4 transcripts increased in type‐1 and type‐2 populations. CCR3 and CCR5 signals were too weak to establish differences. CCR8 transcripts were not increased among unstimulated populations. Compared to naïve, type‐1 and type‐2 populations had reduced CCR7 and enhanced CXCR5 transcripts, consistent with a shift to memory cells. Subset depletion revealed that transcript expression was induced among CD44+ memory T cells. Surprisingly, CCR3 transcripts were enriched among CD44lo fractions. Ag stimulation augmented CXCR3, CCR4, and CCR8 but down‐regulated CCR6 and CXCR5. CCR4 showed association with IFN‐γ‐ and IL‐4‐producing cells, but other receptor transcripts were expressed among IFN‐γ/IL‐4 negative memory T cells. These studies provide several novel findings regarding Th cell chemokine receptor expression in vivo.
Electroluminescence Devices Based on Si Quantum Dots/SiC Multilayers Embedded in PN Junction

We deposited a p-i-n structure device with alternative amorphous Si (a-Si) and amorphous SiC (a-SiC) multilayers as an intrinsic layer in a plasma-enhanced chemical vapor deposition (PECVD) system. A KrF pulsed excimer laser-induced crystallization of a-Si/a-SiC stacked structures was used to prepare Si quantum dots (Si QDs)/SiC multilayers. The formation of Si QDs with an average size of 4 nm was confirmed by Raman spectra, whereas the layered structures were revealed by cross-sectional transmission electron microscopy. Electroluminescence (EL) devices containing Si QDs/SiC multilayers embedded in a p-n junction were fabricated, and the device performance was studied and compared with the reference device without the p-i-n structure. It was found that the turn-on voltage was reduced and that luminescence efficiency was significantly enhanced by using the p-i-n device structure. The recombination mechanism of carriers in a Si-QD-based EL device was also discussed, and the improved device performance can be attributed to the enhanced radiative recombination probability in a p-i-n EL device.
Assessment of thermal network models for estimating IGBT junction temperature of a buck converter

Accurate estimation of semiconductors' junction temperature is particularly important that the impact of the temperature on their reliability and performance is evident. The analysis in this paper reveals that the using of RC thermal network models with reduced number of layers can be tremendously useful. Additionally, a simple technique for transforming n-layer Foster model to a one-cell Cauer ladder model is proposed. The one-cell Cauer model implemented by state-space equations can accelerate calculations. This study also presents a finite element method (FEM) validation based on the real IGBT module geometry for the analyses. A buck converter is considered as the case study. The obtained results show that the one-layer Cauer model can provide the exact outcomes. The difference between the thermal impedance curves is considerable; however, both curves have almost the same peak value.
env Chimeric Virus Technology for Evaluating Human Immunodeficiency Virus Susceptibility to Entry Inhibitors

ABSTRACT We describe the development of chimeric virus technology (CVT) for human immunodeficiency virus (HIV) type 1 (HIV-1) env genes gp120, gp41, and gp160 for evaluation of the susceptibilities of HIV to entry inhibitors. This env CVT allows the recombination of env sequences derived from different strains into a proviral wild-type HIV-1 clone (clone NL4.3) from which the corresponding env gene has been deleted. An HIV-1 strain (strain NL4.3) resistant to the fusion inhibitor T20 (strain NL4.3/T20) was selected in vitro in the presence of T20. AMD3100-resistant strain NL3.4 (strain NL4.3/AMD3100) was previously selected by De Vreese et al. (K. De Vreese et al., J. Virol. 70:689-696, 1996). NL4.3/AMD3100 contains several mutations in its gp120 gene (De Vreese et al., J. Virol. 70:689-696, 1996), whereas NL4.3/T20 has mutations in both gp120 and gp41. Phenotypic analysis revealed that NL4.3/AMD3100 lost its susceptibility to dextran sulfate, AMD3100, AMD2763, T134, and T140 but not its susceptibility to T20, whereas NL4.3/T20 lost its susceptibility only to the inhibitory effect of T20. The recombination of gp120 of NL4.3/AMD3100 and gp41 of NL4.3/T20 or recombination of the gp160 genes of both strains into a wild-type background reproduced the phenotypic (cross-)resistance profiles of the corresponding strains selected in vitro. These data imply that mutations in gp120 alone are sufficient to reproduce the resistance profile of NL4.3/AMD3100. The same can be said for gp41 in relation to NL4.3/T20. In conclusion, we demonstrate the use of env CVT as a research tool in the delineation of the region important for the phenotypic (cross-)resistance of HIV strains to entry inhibitors. In addition, we obtained a proof of principle that env CVT can become a helpful diagnostic tool in assessments of the phenotypic resistance of clinical HIV isolates to HIV entry inhibitors.
Nonnegative Matrix Factorization with Side Information for Time Series Recovery and Prediction

Motivated by the recovery and prediction of electricity consumption time series, we extend Nonnegative Matrix Factorization to take into account external features as side information. We consider general linear measurement settings, and propose a framework which models non-linear relationships between external features and the response variable. We extend previous theoretical results to obtain a sufficient condition on the identifiability of NMF with side information. Based on the classical Hierarchical Alternating Least Squares (HALS) algorithm, we propose a new algorithm (HALSX, or Hierarchical Alternating Least Squares with eXogeneous variables) which estimates NMF in this setting. The algorithm is validated on both simulated and real electricity consumption datasets as well as a recommendation system dataset, to show its performance in matrix recovery and prediction for new rows and columns.
Using Artificial Intelligence to Improve Real-Time Decision-Making for High-Impact Weather

AbstractHigh-impact weather events, such as severe thunderstorms, tornadoes, and hurricanes, cause significant disruptions to infrastructure, property loss, and even fatalities. High-impact events can also positively impact society, such as the impact on savings through renewable energy. Prediction of these events has improved substantially with greater observational capabilities, increased computing power, and better model physics, but there is still significant room for improvement. Artificial intelligence (AI) and data science technologies, specifically machine learning and data mining, bridge the gap between numerical model prediction and real-time guidance by improving accuracy. AI techniques also extract otherwise unavailable information from forecast models by fusing model output with observations to provide additional decision support for forecasters and users. In this work, we demonstrate that applying AI techniques along with a physical understanding of the environment can significantly improve .
Comparison of optical and SAR data in tropical land cover classification for REDD

A comparison study was performed to evaluate the applicability of optical and SAR data for land cover classification for REDD+ services on a test site in Chiapas State in Mexico. The accuracy of the maps was assessed using an independent data set that was collected from very high resolution optical data. The overall accuracy of the maps varied between 79 % of ENVISAT ASAR and 94 % of RapidEye for the forest – non-forest classifications. The accuracies for the six IPCC compliant classes were from 5 to 9 percentage units lower. Results that were obtained with the optical data were somewhat better than the results using the SAR data. However, the difference between the optical and SAR results was fairly small when L-band SAR data were used. L-band SAR data seem to be competitive alternative for optical data particularly in the areas with frequent cloud cover.
Rumen Microbiome Composition Determined Using Two Nutritional Models of Subacute Ruminal Acidosis

ABSTRACT Subacute ruminal acidosis (SARA) is a metabolic disease in dairy cattle that occurs during early and mid-lactation and has traditionally been characterized by low rumen pH, but lactic acid does not accumulate as in acute lactic acid acidosis. It is hypothesized that factors such as increased gut permeability, bacterial lipopolysaccharides, and inflammatory responses may have a role in the etiology of SARA. However, little is known about the nature of the rumen microbiome during SARA. In this study, we analyzed the microbiome of 64 rumen samples taken from eight lactating Holstein dairy cattle using terminal restriction fragment length polymorphisms (TRFLP) of 16S rRNA genes and real-time PCR. We used rumen samples from two published experiments in which SARA had been induced with either grain or alfalfa pellets. The results of TRFLP analysis indicated that the most predominant shift during SARA was a decline in gram-negative Bacteroidetes organisms. However, the proportion of Bacteroidetes organisms was greater in alfalfa pellet-induced SARA than in mild or severe grain-induced SARA (35.4% versus 26.0% and 16.6%, respectively). This shift was also evident from the real-time PCR data for Prevotella albensis, Prevotella brevis, and Prevotella ruminicola, which are members of the Bacteroidetes. The real-time PCR data also indicated that severe grain-induced SARA was dominated by Streptococcus bovis and Escherichia coli, whereas mild grain-induced SARA was dominated by Megasphaera elsdenii and alfalfa pellet-induced SARA was dominated by P. albensis. Using discriminant analysis, the severity of SARA and degree of inflammation were highly correlated with the abundance of E. coli and not with lipopolysaccharide in the rumen. We thus suspect that E. coli may be a contributing factor in disease onset.