Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional Analysis of Glycosyltransferase Genes from Lactococcus lactis and Other Gram-Positive Cocci: Complementation, Expression, and Diversity

ABSTRACT Sixteen exopolysaccharide (EPS)-producing Lactococcus lactis strains were analyzed for the chemical compositions of their EPSs and the locations, sequences, and organization of theeps genes involved in EPS biosynthesis. This allowed the grouping of these strains into three major groups, representatives of which were studied in detail. Previously, we have characterized theeps gene cluster of strain NIZO B40 (group I) and determined the function of three of its glycosyltransferase (GTF) genes. Fragments of the eps gene clusters of strains NIZO B35 (group II) and NIZO B891 (group III) were cloned, and these encoded the NIZO B35 priming galactosyltransferase, the NIZO B891 priming glucosyltransferase, and the NIZO B891 galactosyltransferase involved in the second step of repeating-unit synthesis. The NIZO B40 priming glucosyltransferase gene epsD was replaced with an erythromycin resistance gene, and this resulted in loss of EPS production. This epsD deletion was complemented with priming GTF genes from gram-positive organisms with known function and substrate specificity. Although no EPS production was found with priming galactosyltransferase genes from L. lactis orStreptococcus thermophilus, complementation with priming glucosyltransferase genes involved in L. lactis EPS andStreptococcus pneumoniae capsule biosynthesis could completely restore or even increase EPS production in L. lactis.
Analysis of Generalized Selection Diversity Systems in Wireless Channels

Motivated by practical considerations in the design of low-complexity receiver structures for wideband cellular code division multiple access, millimeter wave, and ultrawideband communications, the study on the generalized selection combining (GSC) receiver that adaptively combines a subset of M "strongest" paths out of L available paths has intensified over the past few years. This paper derives concise analytical expressions for the moment generating function (MGF) of the GSC(M,L) output signal-to-noise ratio when the fading statistics are independent and identically distributed. The novelty of this mathematical framework in computing the MGF relies on the fact that it allows all common multipath fading channel models (Rayleigh, Rician, Nakagami-m, and Nakagami-q) to be treated in a unified sense. It also leads to a much more computationally efficient formula than those available in the literature and is valid for any combinations of M and L values. Using these newly derived MGFs, a unified error probability analysis for many coherent and noncoherent digital-modulation/detection schemes in a myriad of fading environments was provided
Increased Proliferation of the Pancreatic Duct Gland Compartment in Type 1 Diabetes

Context Pancreatic duct glands (PDGs) have been proposed as a source of regeneration in response to exocrine pancreas injury, and thus may serve as an organ stem cell niche. There is evidence to suggest ongoing β-cell formation in longstanding type 1 diabetes (T1D), but the source is unknown. Objective To investigate the PDG compartment of the pancreas in humans with T1D for evidence of an active regenerative signature (presence of progenitor cells and increased proliferation) and, in particular, as a potential source of β-cells. Design, Setting, and Participants Pancreases from 46 brain dead organ donors (22 with T1D, 24 nondiabetic controls) were investigated for activation (increased proliferation) and markers of pancreatic exocrine and endocrine progenitors. Results PDG cell replication was increased in T1D (6.3% ± 1.6% vs 0.6% ± 0.1%, P < 0.001, T1D vs nondiabetic), most prominently in association with pancreatic inflammation. There were increased progenitor-like cells in PDGs of T1D, but predominantly with an exocrine fate. Conclusion The PDG compartment is activated in T1D consistent with a response to ongoing inflammation, and via resulting ductal hyperplasia may contribute to local obstructive pancreatitis and eventual pancreatic atrophy characteristic of T1D. However, there is no evidence of effective endocrine cell formation from PDGs.
Continuous Time Dynamic Topic Models

In this paper, we develop the continuous time dynamic topic model (cDTM). The cDTM is a dynamic topic model that uses Brownian motion to model the latent topics through a sequential collection of documents, where a "topic" is a pattern of word use that we expect to evolve over the course of the collection. We derive an efficient variational approximate inference algorithm that takes advantage of the sparsity of observations in text, a property that lets us easily handle many time points. In contrast to the cDTM, the original discrete-time dynamic topic model (dDTM) requires that time be discretized. Moreover, the complexity of variational inference for the dDTM grows quickly as time granularity increases, a drawback which limits fine-grained discretization. We demonstrate the cDTM on two news corpora, reporting both predictive perplexity and the novel task of time stamp prediction.
Numerical Study on the Comparison of Deformation Characteristics during the Fine Blanking Process of Spur Gears and Helical Gear

As important transmission components, helical gears have been widely applied to mechanical and automotive fields. The traditional manufacturing process for helical gears is machining, which is time-consuming and result in the high cost of gears. In order to improve the production efficiency and product quality of helical gears, a novel forming process principle for the fine blanking of helical gears was developed. In this study, reliable three-dimensional (3D) rigid-plastic finite element (FE) models of single tooth and complete gears were set up and investigated using the software Deform-3D, the deformation characteristics of fine blanking of spur gears and helical gears were compared. Based on the valid numerical models, variation tendency of different field variables such as damage material flow velocity, and mean stress were obtained, as well as the feature of the tooth section, which provides a better understanding of the deformation mechanism of rotational fine blanking process.
Position and motions of the S4 helix during opening of the Shaker potassium channel

The four voltage sensors in voltage-gated potassium (Kv) channels activate upon membrane depolarization and open the pore. The location and motion of the voltage-sensing S4 helix during the early activation steps and the final opening transition are unresolved. We studied Zn2+ bridges between two introduced His residues in Shaker Kv channels: one in the R1 position at the outer end of the S4 helix (R362H), and another in the S5 helix of the pore domain (A419H or F416H). Zn2+ bridges readily form between R362H and A419H in open channels after the S4 helix has undergone its final motion. In contrast, a distinct bridge forms between R362H and F416H after early S4 activation, but before the final S4 motion. Both bridges form rapidly, providing constraints on the average position of S4 relative to the pore. These results demonstrate that the outer ends of S4 and S5 remain in close proximity during the final opening transition, with the S4 helix translating a significant distance normal to the membrane plane.
Characterization of Spores of Bacillus subtilis That Lack Most Coat Layers

ABSTRACT Spores of Bacillus subtilis have a thick outer layer of relatively insoluble protein called the coat, which protects spores against a number of treatments and may also play roles in spore germination. However, elucidation of precise roles of the coat in spore properties has been hampered by the inability to prepare spores lacking all or most coat material. In this work, we show that spores of a strain with mutations in both the cotE and gerE genes, which encode proteins involved in coat assembly and expression of genes encoding coat proteins, respectively, lack most extractable coat protein as seen by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, as well as the great majority of the coat as seen by atomic force microscopy. However, the cotE gerE spores did retain a thin layer of insoluble coat material that was most easily seen by microscopy following digestion of these spores with lysozyme. These severely coat-deficient spores germinated relatively normally with nutrients and even better with dodecylamine but not with a 1:1 chelate of Ca2+ and dipicolinic acid. These spores were also quite resistant to wet heat, to mechanical disruption, and to treatment with detergents at an elevated temperature and pH but were exquisitely sensitive to killing by sodium hypochlorite. These results provide new insight into the role of the coat layer in spore properties.
High and Medium Resolution Satellite Imagery to Evaluate Late Holocene Human-Environment Interactions in Arid Lands: A Case Study from the Central Sahara

We present preliminary results of an Earth observation approach for the study of past human occupation and landscape reconstruction in the Central Sahara. This region includes a variety of geomorphological features such as palaeo-oases, dried river beds, alluvial fans and upland plateaux whose geomorphological characteristics, in combination with climate changes, have influenced patterns of human dispersal and sociocultural activities during the late Holocene. In this paper, we discuss the use of medium- and high-resolution remotely sensed data for the mapping of anthropogenic features and paleo- and contemporary hydrology and vegetation. In the absence of field inspection in this inaccessible region, we use different remote sensing methods to first identify and classify archaeological features, and then explore the geomorphological factors that might have influenced their spatial distribution.
Comparison of real-time instruments and gravimetric method when measuring particulate matter in a residential building

ABSTRACT This study used several real-time and filter-based aerosol instruments to measure PM2.5 levels in a high-rise residential green building in the Northeastern US and compared performance of those instruments. PM2.5 24-hr average concentrations were determined using a Personal Modular Impactor (PMI) with 2.5 µm cut (SKC Inc., Eighty Four, PA) and a direct reading pDR-1500 (Thermo Scientific, Franklin, MA) as well as its filter. 1-hr average PM2.5 concentrations were measured in the same apartments with an Aerotrak Optical Particle Counter (OPC) (model 8220, TSI, Inc., Shoreview, MN) and a DustTrak DRX mass monitor (model 8534, TSI, Inc., Shoreview, MN). OPC and DRX measurements were compared with concurrent 1-hr mass concentration from the pDR-1500. The pDR-1500 direct reading showed approximately 40% higher particle mass concentration compared to its own filter (n = 41), and 25% higher PM2.5 mass concentration compared to the PMI2.5 filter. The pDR-1500 direct reading and PMI2.5 in non-smoking homes (self-reported) were not significantly different (n = 10, R2 = 0.937), while the difference between measurements for smoking homes was 44% (n = 31, R2 = 0.773). Both OPC and DRX data had substantial and significant systematic and proportional biases compared with pDR-1500 readings. However, these methods were highly correlated: R2 = 0.936 for OPC versus pDR-1500 reading and R2 = 0.863 for DRX versus pDR-1500 reading. The data suggest that accuracy of aerosol mass concentrations from direct-reading instruments in indoor environments depends on the instrument, and that correction factors can be used to reduce biases of these real-time monitors in residential green buildings with similar aerosol properties. Implications: This study used several real-time and filter-based aerosol instruments to measure PM2.5 levels in a high-rise residential green building in the northeastern United States and compared performance of those instruments. The data show that while the use of real-time monitors is convenient for measurement of airborne PM at short time scales, the accuracy of those monitors depends on a particular instrument. Bias correction factors identified in this paper could provide guidance for other studies using direct-reading instruments to measure PM concentrations.
Computational modeling of the immune response to tumor antigens: implications for vaccination

Vaccination protocols designed to elicit anti-cancer immune responses have, in most cases, failed in producing tumor eradication and in prolonging patient survival. Usually in cancer vaccination, epitopes from one organism are included in the genome or linked with some protein of another (named carrier) in the hope that the immunogenic properties of the latter will boost an immune response to the former. However, recent results have demonstrated that injections of two different vectors encoding the same recombinant antigen generate high levels of specific immunity. Systematic comparison of the efficacy of different vaccination protocols has been hampered by technical limitations and a clear evidence that the use of multiple vectors has advantage over single carrier injections is lacking. We used a computational model to investigate the dynamics of the immune response to different anti-cancer vaccines based on randomly generated antigen/carrier compounds. More than 3000 simulations of the immune response to tumor were performed. Notably, the model has been extensively validated and it reproduces a relevant number of experimental observations. The model shows that when priming and boosting with the same construct, competition rather than cooperation develops amongst T cell clones of different specificities. Moreover, from the simulations, it appears that the sequential use of multiple carriers may generate more robust anti-tumor immune responses and may lead to effective tumor eradication in a higher percentage of cases. Our results provide a rational background for the design of novel strategies for the achievement of immune control of cancer.
The Late Developmental Pattern of Mu Transposon Excision Is Conferred by a Cauliflower Mosaic Virus 35S–Driven MURA cDNA in Transgenic Maize

The MuDR element responsible for Mutator activities in maize encodes two genes, mudrA and mudrB. Each encodes multiple transcripts hypothesized to regulate, directly or indirectly, the unique late timing and switch in transposition mechanism during maize development. mudrA, which encodes the MURA transposase, is unstable in bacterial plasmids, a technical problem solved by using phage M13 as a vector to prepare DNA for biolistic transformation. In transgenic maize, a single 2.7-kb mudrA cDNA predicted to encode an 823–amino acid protein is sufficient to catalyze late somatic excisions, despite removal of the native promoter, alternative transcription start sites, known introns, polymorphic 5′ and 3′ untranslated sequences, and the mudrB gene. These results suggest that post-translational regulation confers Mu excision timing. The transgene is active in lines containing silencing MuDR elements. This suggests that endogenous MuDR transposons do not measurably immunize the host against expression of a homologous transgene.
Bayesian model averaging: development of an improved multi-class, gene selection and classification tool for microarray data

MOTIVATION Selecting a small number of relevant genes for accurate classification of samples is essential for the development of diagnostic tests. We present the Bayesian model averaging (BMA) method for gene selection and classification of microarray data. Typical gene selection and classification procedures ignore model uncertainty and use a single set of relevant genes (model) to predict the class. BMA accounts for the uncertainty about the best set to choose by averaging over multiple models (sets of potentially overlapping relevant genes). RESULTS We have shown that BMA selects smaller numbers of relevant genes (compared with other methods) and achieves a high prediction accuracy on three microarray datasets. Our BMA algorithm is applicable to microarray datasets with any number of classes, and outputs posterior probabilities for the selected genes and models. Our selected models typically consist of only a few genes. The combination of high accuracy, small numbers of genes and posterior probabilities for the predictions should make BMA a powerful tool for developing diagnostics from expression data. AVAILABILITY The source codes and datasets used are available from our Supplementary website.
The safety of vedolizumab for ulcerative colitis and Crohn's disease

Objective Vedolizumab is a gut-selective antibody to α4β7 integrin for the treatment of ulcerative colitis (UC) and Crohn's disease (CD). We report an integrated summary of the safety of vedolizumab. Design Safety data (May 2009–June 2013) from six trials of vedolizumab were integrated. Adverse events were evaluated in patients who received ≥1 dose of vedolizumab or placebo and were reported as exposure-adjusted incidence rates as the number of patients experiencing the event per 100 person-years (PYs) of exposure. Predictors of serious infection were assessed using a Cox proportional hazards model. Results In total, 2830 patients had 4811 PYs of vedolizumab exposure (median exposure range, 1–1977 days). No increased risk of any infection or serious infection was associated with vedolizumab exposure. Serious clostridial infections, sepsis and tuberculosis were reported infrequently (≤0.6% of patients). No cases of progressive multifocal leucoencephalopathy were observed. Independent risk factors for serious infection in UC were prior failure of a tumour necrosis factor α antagonist (HR, 1.99; 95% CIs 1.16 to 3.42; p=0.0122) and narcotic analgesic use (HR, 2.68; 95% CI 1.57 to 4.58; p=0.0003), and in CD were younger age (HR, 0.97; 95% CI 0.95 to 0.98; p<0.0001), corticosteroid (HR, 1.88; 95% CI 1.35 to 2.63; p=0.0002) or narcotic analgesic use (HR, 2.72; 95% CI 1.90 to 3.89; p<0.0001). Investigator-defined infusion-related reactions were reported for ≤5% of patients in each study. Eighteen vedolizumab-exposed patients (<1%) were diagnosed with a malignancy. Conclusions Vedolizumab has a favourable safety profile with low incidence rates of serious infections, infusion-related reactions and malignancies over an extended treatment period. Trial registration number NCT01177228, NCT00619489, NCT00783718, NCT00783692, NCT01224171, NCT00790933.
Designing Committees of Models through Deliberate Weighting of Data Points

In the adaptive derivation of mathematical models from data, each data point should contribute with a weight reflecting the amount of confidence one has in it. When no additional information for data confidence is available, all the data points should be considered equal, and are also generally given the same weight. In the formation of committees of models, however, this is often not the case and the data points may exercise unequal, even random, influence over the committee formation. In this paper, a principled approach to committee design is presented. The construction of a committee design matrix is detailed through which each data point will contribute to the committee formation with a fixed weight, while contributing with different individual weights to the derivation of the different constituent models, thus encouraging model diversity whilst not biasing the committee inadvertently towards any particular data points. Not distinctly an algorithm, it is instead a framework within which several different committee approaches may be realised. Whereas the focus in the paper lies entirely on regression, the principles discussed extend readily to classification.
Atypical Secretions of the Male Cephalic Labial Glands in Bumblebees: The Case of Bombus (Rhodobombus) mesomelas Gerstaecker (Hymenoptera, Apidae)

In bumblebees, the male secretion of the cephalic labial gland is species‐specific. It is highly involved in the nuptial behavior, acting as a sexual attracting pheromone. Therefore, it is also used to accurately identify the species. In contrast to this common scheme, the secretions of Bombus mesomelas are found to be strongly reduced and do not include the most volatile compounds that are present in the secretions of all the other studied bumblebee species. These secretions correspond to cuticular hydrocarbons that can be found in all bumblebee species. This was also the case for another bumblebee species from the same Rhodobombus subgenus: Bombus pomorum. This atypical composition of the male cephalic labial gland secretions seems to indicate that, at least for these two species of Rhodobombus, these secretions are not used to attract virgin females from a long distance, as it is the case for all the other bumblebee species studied.
A Bioengineered Nisin Derivative, M21A, in Combination with Food Grade Additives Eradicates Biofilms of Listeria monocytogenes

The burden of foodborne disease has large economic and social consequences worldwide. Despite strict regulations, a number of pathogens persist within the food environment, which is greatly contributed to by a build-up of resistance mechanisms and also through the formation of biofilms. Biofilms have been shown to be highly resistant to a number of antimicrobials and can be extremely difficult to remove once they are established. In parallel, the growing concern of consumers regarding the use of chemically derived antimicrobials within food has led to a drive toward more natural products. As a consequence, the use of naturally derived antimicrobials has become of particular interest. In this study we investigated the efficacy of nisin A and its bioengineered derivative M21A in combination with food grade additives to treat biofilms of a representative foodborne disease isolate of Listeria monocytogenes. Investigations revealed the enhanced antimicrobial effects, in liquid culture, of M21A in combination with citric acid or cinnamaldehyde over its wild type nisin A counterpart. Subsequently, an investigation was conducted into the effects of these combinations on an established biofilm of the same strain. Nisin M21A (0.1 μg/ml) alone or in combination with cinnamaldehyde (35 μg/ml) or citric acid (175 μg/ml) performed significantly better than combinations involving nisin A. All combinations of M21A with either citric acid or cinnamaldehyde eradicated the L. monocytogenes biofilm (in relation to a non-biofilm control). We conclude that M21A in combination with available food additives could further enhance the antimicrobial treatment of biofilms within the food industry, simply by substituting nisin A with M21A in current commercial products such as Nisaplin® (Danisco, DuPont).
Genetic and Biochemical Analysis of Yeast and Human Cap Trimethylguanosine Synthase

Trimethylguanosine synthase (Tgs1) is the enzyme that converts standard m7G caps to the 2,2,7-trimethylguanosine (TMG) caps characteristic of spliceosomal small nuclear RNAs. Fungi and mammalian somatic cells are able to grow in the absence of Tgs1 and TMG caps, suggesting that an essential function of the TMG cap might be obscured by functional redundancy. A systematic screen in budding yeast identified nonessential genes that, when deleted, caused synthetic growth defects with tgs1Δ. The Tgs1 interaction network embraced proteins implicated in small nuclear ribonucleoprotein function and spliceosome assembly, including Mud2, Nam8, Brr1, Lea1, Ist3, Isy1, Cwc21, and Bud13. Complementation of the synthetic lethality of mud2Δ tgs1Δ and nam8Δ tgs1Δ strains by wild-type TGS1, but not by catalytically defective mutants, indicated that the TMG cap is essential for mitotic growth when redundant splicing factors are missing. Our genetic analysis also highlighted synthetic interactions of Tgs1 with proteins implicated in RNA end processing and decay (Pat1, Lsm1, and Trf4) and regulation of polymerase II transcription (Rpn4, Spt3, Srb2, Soh1, Swr1, and Htz1). We find that the C-terminal domain of human Tgs1 can function in lieu of the yeast protein in vivo. We present a biochemical characterization of the human Tgs1 guanine-N2 methyltransferase reaction and identify individual amino acids required for methyltransferase activity in vitro and in vivo.