Miracle-dz/UniFAR-FTUs huggingface dataset:
Stimulation of Methanotrophic Growth in Cocultures by Cobalamin Excreted by Rhizobia

ABSTRACT Methanotrophs play a key role in the global carbon cycle, in which they affect methane emissions and help to sustain diverse microbial communities through the conversion of methane to organic compounds. To investigate the microbial interactions that cause positive effects on methanotrophs, cocultures were constructed using Methylovulum miyakonense HT12 and each of nine nonmethanotrophic bacteria, which were isolated from a methane-utilizing microbial consortium culture established from forest soil. Three rhizobial strains were found to strongly stimulate the growth and methane oxidation of M. miyakonense HT12 in cocultures. We purified the stimulating factor produced by Rhizobium sp. Rb122 and identified it as cobalamin. Growth stimulation by cobalamin was also observed for three other gammaproteobacterial methanotrophs. These results suggest that microbial interactions through cobalamin play an important role in methane oxidation in various ecosystems.
Immune dysregulation accelerates atherosclerosis and modulates plaque composition in systemic lupus erythematosus.

Patients with systemic lupus erythematosus (SLE) have accelerated atherosclerosis. The underlying mechanisms are poorly understood, and investigations have been hampered by the absence of animal models that reflect the human condition of generalized atherosclerosis and lupus. We addressed this problem by transferring lupus susceptibility to low-density lipoprotein (LDL) receptor-deficient (LDLr-/-) mice, an established model of atherosclerosis, creating radiation chimeras with NZM2410-derived, lupus-susceptible, B6.Sle1. 2.3 congenic or C57BL/6 control donors (LDLr.Sle and LDLr.B6, respectively). LDLr.Sle mice developed a lupus-like disease characterized by production of double-stranded DNA autoantibodies and renal disease. When fed a Western-type diet, LDLr.Sle chimeras had increased mortality and atherosclerotic lesions. The plaques of LDLr.Sle mice were highly inflammatory and contained more CD3+ T cells than controls. LDLr.Sle mice also had increased activation of CD4+ T and B cells and significantly higher antibody to oxidized LDL and cardiolipin. Collectively, these studies demonstrate that the lupus-susceptible immune system enhances atherogenesis and modulates plaque composition.
Small Molecule Therapeutics Selective Inhibition of Pancreatic Ductal Adenocarcinoma Cell Growth by the Mitotic MPS 1 Kinase Inhibitor NMSP 715

Most solid tumors, including pancreatic ductal adenocarcinoma (PDAC), exhibit structural and numerical chromosome instability (CIN). Although often implicated as a driver of tumor progression and drug resistance, CIN also reduces cell fitness and poses a vulnerability that can be exploited therapeutically. The spindle assembly checkpoint (SAC) ensures correct chromosome-microtubule attachment, thereby minimizing chromosome segregation errors. Many tumors exhibit upregulation of SAC components such as MPS1, which may help contain CIN within survivable limits. Prior studies showed that MPS1 inhibition with the small molecule NMS-P715 limits tumor growth in xenograft models. In cancer cell lines, NMSP715 causes cell death associated with impaired SAC function and increased chromosome missegregation. Although normal cells appeared more resistant, effects on stem cells, which are the dose-limiting toxicity of most chemotherapeutics, were not examined. Elevated expression of 70 genes (CIN70), including MPS1, provides a surrogate measure of CIN and predicts poor patient survival in multiple tumor types. Our new findings show that the degree of CIN70 upregulation varies considerably among PDAC tumors, with higher CIN70 gene expression predictive of poor outcome. We identified a 25 gene subset (PDAC CIN25) whose overexpression was most strongly correlated with poor survival and included MPS1. In vitro, growth of human and murine PDAC cells is inhibited by NMS-P715 treatment, whereas adipose-derived human mesenchymal stem cells are relatively resistant and maintain chromosome stability upon exposure to NMS-P715. These studies suggest that NMS-P715 could have a favorable therapeutic index and warrant further investigation of MPS1 inhibition as a new PDAC treatment strategy.Mol Cancer Ther; 13(2); 307–15.
Association of Chlamydia trachomatis Infection and Herpes Simplex Virus Type 2 Serostatus With Genital Human Papillomavirus Infection in Men: The HPV in Men Study

Background Studies in women indicate that some sexually transmitted infections promote human papillomavirus (HPV) persistence and carcinogenesis. Little is known about this association in men; therefore, we assessed whether Chlamydia trachomatis (CT) infection and herpes simplex virus type 2 (HSV-2) serostatus are associated with genital HPV prevalence, an early event in HPV-related pathogenesis. Methods Genital exfoliated cells, first-void urine, and blood from 3971 men recruited in the United States, Mexico, and Brazil were tested for HPV, CT, and HSV-2 antibodies, respectively. Multivariable logistic regression was used to assess the association of CT infection and HSV-2 serostatus with 4 HPV outcomes (any, oncogenic, nononcogenic only, and multiple infections). Results A total of 64 (1.6%) men were CT positive, and 811 (20.4%) men were HSV-2 seropositive. After adjustment for potential confounders, CT was associated with any HPV (adjusted odds ratio [aOR], 2.19; 95% confidence interval [CI], 1.13–4.24), oncogenic HPV (aOR, 3.10; 95% CI, 1.53–6.28), and multiple HPV (aOR, 3.43; 95% CI, 1.69–6.95) prevalence. Herpes simplex virus type 2 serostatus was associated with any HPV (aOR, 1.25; 95% CI, 1.02–1.52), nononcogenic HPV only (aOR, 1.38; 95% CI, 1.08–1.75), and multiple HPV (aOR, 1.33; 95% CI, 1.06–1.68) prevalence. In analyses stratified by sexual behavior, CT infection was significantly associated with HPV detection among men reporting 2 or more recent sexual partners, whereas HSV-2 serostatus was significantly associated with HPV detection in men reporting 0 to 5 lifetime sexual partners. Conclusion In this population, CT infection and HSV-2 serostatus were associated with prevalent genital HPV infection. Future prospective studies should investigate whether these infections influence HPV acquisition and/or persistence.
Fracture Resistance and Fatigue Crack Growth of X80 Pipeline Steel in Gaseous Hydrogen

Gaseous hydrogen is a convenient medium to store and transport energy. As existing petroleum-based platforms are electrified, such as with the growth of fuel cell systems, hydrogen is becoming an attractive fuel which must be distributed, stored and dispensed. Hydrogen is used extensively in refining of petroleum products, and often distributed by pipeline. However, there remains a need to quantify the mechanical properties of low-cost steels in gaseous hydrogen and to relate the measured performance to the variety of microstructures that characterize steels. This study is part of a larger effort to characterize a broad range of steels manufactured for pipelines and to measure their fracture and fatigue resistance in gaseous hydrogen. The fracture resistance and fatigue crack growth rates of two microstructural variations of X80 pipeline steel were measured in gaseous hydrogen at pressure of 21 MPa. The performance of these steels was found to be similar to the performance of other ferritic steels that are currently used to distribute gaseous hydrogen.Copyright © 2011 by ASME
Elevation and persistence of CD8 T-cells in HIV infection: the Achilles heel in the ART era

HIV infection leads to a disturbed T‐cell homeostasis, featured by a depletion of CD4 T‐cells and a persistent elevation of CD8 T‐cells over disease progression. Most effort of managing HIV infection has been focused on CD4 T‐cell recovery, while changes in the CD8 compartment were relatively underappreciated in the past.
Methanol-Promoted Lipid Remodelling during Cooling Sustains Cryopreservation Survival of Chlamydomonas reinhardtii

Cryogenic treatments and cryoprotective agents (CPAs) determine the survival rate of organisms that undergo cryopreservation, but their mechanisms of operation have not yet been characterised adequately. In particular, the way in which membrane lipids respond to cryogenic treatments and CPAs is unknown. We developed comparative profiles of the changes in membrane lipids among cryogenic treatments and between the CPAs dimethyl sulfoxide (DMSO) and methanol (MeOH) for the green alga Chlamydomonas reinhardtii. We found that freezing in liquid nitrogen led to a dramatic degradation of lipids, and that thawing at warm temperature (35°C) induced lipid remodelling. DMSO did not protect membranes, but MeOH significantly attenuated lipid degradation. The presence of MeOH during cooling (from 25°C to −55°C at a rate of 1°C/min) sustained the lipid composition to the extent that membrane integrity was maintained; this phenomenon accounts for successful cryopreservation. An increase in monogalactosyldiacylglycerol and a decrease in diacylglycerol were the major changes in lipid composition associated with survival rate, but there was no transformation between these lipid classes. Phospholipase D-mediated phosphatidic acid was not involved in freezing-induced lipid metabolism in C. reinhardtii. Lipid unsaturation changed, and the patterns of change depended on the cryogenic treatment. Our results provide new insights into the cryopreservation of, and the lipid metabolism in, algae.
Phosphorylation-mediated inactivation of coactivator-associated arginine methyltransferase 1

Multiple protein arginine methyltransferases are involved in transcriptional activation of nuclear receptors. Coactivator-associated arginine methyltransferase 1 (CARM1)-mediated histone methylation has been shown to activate nuclear receptor-dependent transcription; however, little is known about the regulation of its enzymatic activity. Here, we report that the methyltransferase activity of CARM1 is negatively regulated through phosphorylation at a conserved serine residue. When the serine residue is mutated to glutamic acid, which mimics the phosphorylated serine residue, the mutant CARM1 exhibits diminished ability to bind the methyl donor adenosylmethionine and diminished histone methylation activity. Moreover, such mutation leads to the inhibition of CARM1 transactivation of estrogen receptor-dependent transcription. Our results provide an example for the regulation of protein arginine methyltransferase activity by phosphorylation. As CARM1 is a potent transcriptional coactivator of estrogen receptor, our results suggest that phosphorylation of CARM1 serves as a unique mechanism for inactivating CARM1-regulated estrogen-dependent gene expression.
Double blind placebo-controlled trial of pleconaril in infants with enterovirus meningitis

Background. Enterovirus (EV) meningitis is common in infants and may have neurologic complications. Treatment of older children and adults with pleconaril has been associated with reduced severity and duration of symptoms. This study evaluated the pharmacokinetics, safety and efficacy of pleconaril in infants with EV meningitis. Methods. Infants ≤12 months old with suspected EV meningitis were randomized 2:1 to receive pleconaril, 5 mg/kg/dose orally three times a day or placebo for 7 days. Evaluations included pharmacokinetic determinations, safety laboratory testing, serial culture and PCR assays and clinical evaluations. Results. Of 21 evaluable subjects 20 were confirmed with EV infection (12 pleconaril, 8 placebo). Among pleconaril-treated subjects 26 of 29 peak and trough pleconaril levels exceeded the 90% inhibitory concentration for EVs. A median 3.5-fold drug accumulation occurred between Days 2 and 7. Pleconaril was well-tolerated, although twice as many adverse events occurred per subject in the pleconaril group. Serial cultures from the oropharynx, rectum and serum had low yield (≤50%) and positivity generally persisted for <4 days in both groups. Serial PCR assays of culture-negative oropharyngeal and rectal specimens had high positivity rates (generally ≥50%) persisting through Day 14. No significant differences in duration of positivity by culture or PCR, hospitalization or symptoms were detected between groups. Conclusions. The dose of pleconaril studied provided sufficient plasma levels and was well-tolerated; however, drug accumulation was evident. The low yields of serial viral cultures, relatively short and benign clinical courses and the small number of subjects enrolled precluded demonstration of efficacy. If this medication is to be prescribed in infants, surveillance for toxicity related to drug accumulation will be necessary.
A global assay of haemostasis which uses recombinant tissue factor and tissue-type plasminogen activator to measure the rate of fibrin formation and fibrin degradation in plasma

Summary The global assay of Overall Haemostasis Potential we previously described has been refined. The coagulation cascade in plateletpoor plasma is triggered by adding a minimal dose of recombinant tissue factor together with purified phospholipids and calcium; fibrinolysis is initiated by adding recombinant tissue type-plasminogen activator in a concentration similar to what can be obtained during thrombolysis. Numerical differentials of optical densities reflecting rates of fibrin formation and degradation are calculated by a new software, and the Coagulation Profile (Cp) and the Fibrinolysis Profile (Fp) are determined. The combined effect of these counteractive systems is expressed as a ratio of Cp to Fp, called the Overall Haemostasis Index. Commercially available coagulant-deficient patient plasma samples and plasma with various amounts of added PAI-1 are examined; changes of fibrin turbidity demonstrate that this assay can determine Cp and Fp in a physiologically relevant way. Increased Cp and decreased Fp in prothrombotic patients, as well as expected effects of heparin or a thrombin inhibitor on Cp and Fp, suggest that our method can detect hypercoagulability and assist in monitoring antithrombotic treatment. Ongoing studies will show whether this simple assay can be of value in clinical routine.
Enhanced Computational Sampling of Perylene and Perylothiophene Packing with Rigid-Body Models

Molecular simulations have the potential to advance the understanding of how the structure of organic materials can be engineered through the choice of chemical components but are limited by computational costs. The computational costs can be significantly lowered through the use of modeling approximations that capture the relevant features of a system, while lowering algorithmic complexity or by decreasing the degrees of freedom that must be integrated. Such methods include coarse-graining techniques, approximating long-range electrostatics with short-range potentials, and the use of rigid bodies to replace flexible bonded constraints between atoms. To understand whether and to what degree these techniques can be leveraged to enhance the understanding of planar organic molecules, we investigate the morphologies predicted by molecular dynamic simulations using simplified molecular models of perylene and perylothiophene. Approximately, 10 000 wall-clock hours of graphics processing unit-accelerated simulations are performed using both rigid and flexible models to test their efficiency and predictive capability with the two chemistries. We characterize the 1191 resulting morphologies using simulated X-ray diffraction and cluster analysis to distinguish structural transitions, summarized by four phase diagrams. We find that the morphologies generated by the rigid model of perylene and perylothiophene match with those generated by the flexible model. We find that ordered, hexagonally packed columnar phases are thermodynamically favored over a wide range of densities and temperatures for both molecules, in qualitative agreement with experiments. Furthermore, we find the rigid model to be more computationally efficient for both molecules, providing more samples per second and shorter times to equilibrium. Owing to the structural accuracy and improved computational efficiency of modeling polyaromatic groups as rigid bodies, we recommend this modeling choice for enhancing the sampling in polyaromatic molecular simulations.
The geometrical structure of 2D bond-orientational order

We study the formulation of bond-orientational order in an arbitrary two-dimensional geometry. We find that bond-orientational order is properly formulated within the framework of differential geometry with torsion. The torsion reflects the intrinsic frustration for two-dimensional crystals with arbitrary geometry. Within a Debye-Huckel approximation, torsion may be identified as the density of dislocations. Changes in the geometry of the system cause a reorganization of the torsion density that preserves bond-orientational order. As a byproduct, we are able to derive several identities involving the topology, defect density and geometric invariants such as Gaussian curvature. The formalism is used to derive the general free energy for a 2D sample of arbitrary geometry, in both the crystalline and hexatic phases. Applications to conical and spherical geometries are briefly addressed.
Data Aggregation Scheduling Algorithms in Wireless Sensor Networks: Solutions and Challenges

Energy limitation is the main concern of any wireless sensor network application. The communication between nodes is the greedy factor for the energy consumption. One important mechanism to reduce energy consumption is the in-network data aggregation. In-network data aggregation removes redundancy as well as unnecessary data forwarding, and hence cuts on the energy used in communications. Recently a new kind of applications are proposed which consider, in addition to energy efficiency, data latency and accuracy as important factors. Reducing data latency helps increasing the network throughput and early events detection. Before performing the aggregation process, each node should wait for a predefined time called WT (waiting time) to receive data from other nodes. Data latency (resp., accuracy) is decreased (resp., increased), if network nodes are well scheduled through optimal distribution of WT over the nodes. Many solutions have been proposed to schedule network nodes in order to make the data aggregation process more efficient. In this paper, we propose a taxonomy and classification of existing data aggregation scheduling solutions. We survey main solutions in the literature and illustrate their operations through examples. Furthermore, we discuss each solution and analyze it against performance criteria such as data latency and accuracy, energy consumption and collision avoidance. Finally, we shed some light on future research directions and open issues after deep analysis of existing solutions.
Dynamic Movement Primitives for Human Robot interaction

A specialization of the generic Dynamic Movement Primitives (DMP) framework is proposed in this article to correctly address a key activity for human robot collaboration that is object exchange. As a first step towards implementing this challenging skill, this paper focuses on the arm motion to reach the initially unknown exchange site. Two improvements related with this application are proposed. First of all a better control of the transition in between the two mains components of the DMP –respectively providing a skill shape-attractor and a goal-attractor– is described, enabling to define when and how the transition in between these two components occur. Then an extension to handle situations where the goal position varies along time is proposed, which improves the convergence of the trajectory towards a moving target (i.e. the human partner’s hand). These two improvements are validated by comparing the obtained behavior with human observations realized through motion capture.
Learning the right model: Efficient max-margin learning in Laplacian CRFs

An important modeling decision made while designing Conditional Random Fields (CRFs) is the choice of the potential functions over the cliques of variables. Laplacian potentials are useful because they are robust potentials and match image statistics better than Gaussians. Moreover, energies with Laplacian terms remain convex, which simplifies inference. This makes Laplacian potentials an ideal modeling choice for some applications. In this paper, we study max-margin parameter learning in CRFs with Laplacian potentials (LCRFs). We first show that structured hinge-loss [35] is non-convex for LCRFs and thus techniques used by previous works are not applicable. We then present the first approximate max-margin algorithm for LCRFs. Finally, we make our learning algorithm scalable in the number of training images by using dual-decomposition techniques. Our experiments on single-image depth estimation show that even with simple features, our approach achieves comparable to state-of-art results.
Report on Measurements of Workability and Rheology of Fresh Concrete

Copyright © 2008, American Concrete Institute. All rights reserved including rights of reproduction and use in any form or by any means, including the making of copies by any photo process, or by electronic or mechanical device, printed, written, or oral, or recording for sound or visual reproduction or for use in any knowledge or retrieval system or device, unless permission in writing is obtained from the copyright proprietors.
Observations on the Role of TcdE Isoforms in Clostridium difficile Toxin Secretion

ABSTRACT Clostridium difficile is a major nosocomial pathogen and the principal causative agent of antibiotic-associated diarrhea. The toxigenic C. difficile strains that cause disease secrete virulence factors, toxin A and toxin B, that cause colonic injury and inflammation. C. difficile toxins have no export signature and are secreted by an unusual mechanism that involves TcdE, a holin-like protein. We isolated a TcdE mutant of the epidemic R20291 strain with impaired toxin secretion, which was restored by complementation with functional TcdE. In the TcdE open reading frame (ORF), we identified three possible translation start sites; each translated isoform may play a specific role in TcdE-controlled toxin release. We created plasmid constructs that express only one of the three TcdE isoforms and complemented the TcdE mutant with these isoforms. Western blot analysis of the complemented strains demonstrated that TcdE is translated efficiently from the start codon at the 25th and 27th positions in the predicted ORF, producing proteins with 142 amino acids (TcdE142) and 140 amino acids (TcdE140), respectively. TcdE166 was not detected when expressed from its own ribosomal binding site (RBS). The effects of all three TcdE isoforms on C. difficile cell viability and toxin release were determined. Among the three isoforms, overexpression of TcdE166 and TcdE142 had a profound effect on cell viability compared to the TcdE140 isoform. Similarly, TcdE166 and TcdE142 facilitated toxin release more efficiently than did TcdE140. The importance of these variations among TcdE isoforms and their role in toxin release are discussed. IMPORTANCE C. difficile is a nosocomial pathogen that has become the most prevalent cause of antibiotic-associated diarrhea in North America and in several countries in Europe. Most strains of C. difficile produce two high-molecular-weight toxins that are regarded as the primary virulence factors. The mechanism by which these large toxins are secreted from bacterial cells is not yet clear but involves TcdE, a holin-like protein. In this work, we show that TcdE could be translated from three different start codons, resulting in the production of three TcdE isoforms. Furthermore, we investigated the role of these isoforms in toxin release and cell lysis in C. difficile. An understanding of TcdE-dependent toxin secretion may be helpful for the development of strategies for preventing and treating C. difficile infections.