gebhart/patrepeval huggingface dataset:
Trehalose 6‐phosphate phosphatases of <i>Pseudomonas aeruginosa</i> (2018)

The opportunistic bacterium Pseudomonas aeruginosa has been recognized as an important pathogen of clinical relevance and is a leading cause of hospital-acquired infections. The presence of a glycolytic enzyme in Pseudomonas, which is known to be inhibited by trehalose 6-phosphate (T6P) in other organisms, suggests that these bacteria may be vulnerable to the detrimental effects of intracellular T6P accumulation. In the present study, we explored the structural and functional properties of trehalose 6-phosphate phosphatase (TPP) in P. aeruginosa in support of future target-based drug discovery. A survey of genomes revealed the existence of 2 TPP genes with either chromosomal or extrachromosomal location. Both TPPs were produced as recombinant proteins, and characterization of their enzymatic properties confirmed specific, magnesium-dependent catalytic hydrolysis of T6P. The 3-dimensional crystal structure of the chromosomal TPP revealed a protein dimer arising through β-sheet expansion of the individual monomers, which possess the overall fold of halo-acid dehydrogenases.-Cross, M., Biberacher, S., Park, S.-Y., Rajan, S., Korhonen, P., Gasser, R. B., Kim, J.-S., Coster, M. J., Hofmann, A. Trehalose 6-phosphate phosphatases of Pseudomonas aeruginosa.
LNG plant design in the 1990`s (1995)

Advances in LNG plant design are needed to improve LNG chain economics. Improving the economics is essential to insure the feasibility of proposed and future projects and will compel new developments. This paper discusses anticipated changes and their significance. Topics include: Technology and Plant Design; Train Capacity; Reliability/Availability. Likely improvements in technology include: new and improved computation and analytical tools; larger and more efficient compressors and mechanical drivers; increased plant life expectancy; improved gas treating for H{sub 2}S, CO{sub 2}, and mercury removal; and the application of recent equipment developments. Train capacities are becoming larger, resulting in improved economics. Discussion on size, bottlenecks, compressor and turbine configurations, economics, and construction techniques are included. Closely related to train capacity and design are the reliability and availability of each LNG train and of the plant common facilities. Methods of analysis and design are presented to attain the desired availability for each train and the entire complex, and to optimize the complete LNG chain (production, liquefaction and storage, shipping, and receiving).
Io, Saturnalia! (2009)

December marks the winter solstice-an astronomical event that happens when the earth′s axis is inclined as far away from the sun as possible
Genetic Modifiers of MeCP2 Function in Drosophila (2008)

The levels of methyl-CpG-binding protein 2 (MeCP2) are critical for normal post-natal development and function of the nervous system. Loss of function of MeCP2, a transcriptional regulator involved in chromatin remodeling, causes classic Rett syndrome (RTT) as well as other related conditions characterized by autism, learning disabilities, or mental retardation. Increased dosage of MeCP2 also leads to clinically similar neurological disorders and mental retardation. To identify molecular mechanisms capable of compensating for altered MeCP2 levels, we generated transgenic Drosophila overexpressing human MeCP2. We find that MeCP2 associates with chromatin and is phosphorylated at serine 423 in Drosophila, as is found in mammals. MeCP2 overexpression leads to anatomical (i.e., disorganized eyes, ectopic wing veins) and behavioral (i.e., motor dysfunction) abnormalities. We used a candidate gene approach to identify genes that are able to compensate for abnormal phenotypes caused by MeCP2 increased activity. These genetic modifiers include other chromatin remodeling genes (Additional sex combs, corto, osa, Sex combs on midleg, and trithorax), the kinase tricornered, the UBE3A target pebble, and Drosophila homologues of the MeCP2 physical interactors Sin3a, REST, and N-CoR. These findings demonstrate that anatomical and behavioral phenotypes caused by MeCP2 activity can be ameliorated by altering other factors that might be more amenable to manipulation than MeCP2 itself.
Robust control methodologies for dc/dc PWM converters under wide changes in operating conditions (2006)

In this paper, a comparative study on the subject of robust control of dc/dc PWM converters is presented. Considering a wide range of possible changes for the converter's operating conditions, robust control of dc/dc PWM converters using some state of the art robust controllers i.e., H∞, µ, and fuzzy controllers is studied. The system under study is a CUK converter as a non-linear, variable structure, and non-minimum phase plant with complex and potentially chaotic behavior. The results confirm successful performance of the H∞ and µ controllers in providing wonderful robustness to even wide changes in the operating point. The results also prove that in compare with the H∞, the µ controller can by far provide superior results. As will be shown, while the results are quit interesting, the ability of such linear controllers is restricted to the situations where a linear model for the under study system is considered. They may fall down to control the exact physical system, especially where the large signal behavior of the converter is studied. To overcome the aforementioned issues, a simple robust fuzzy controller accompanied with a non-linear / time varying feed-forward controller is proposed. The results clearly prove the relative superiority of fuzzy controller design framework, which lead to a non-linear controller, to overcome the stability issues of the complex dc/dc converters.
The Future of Fragile X Syndrome: CDC Stakeholder Meeting Summary (2017)

* Abbreviations:
 ASD — : autism spectrum disorder
 CDC — : Centers for Disease Control and Prevention
 FMR1 — : fragile x mental retardation 1
 FMRP — : fragile X mental retardation protein
 FXD — : fragile X–associated disorder
 FXS — : fragile X syndrome
 ID — : intellectual disability

Fragile X syndrome (FXS) is the most common known inherited cause of intellectual disability (ID). Males and females with FXS exhibit a wide range of intellectual ability and may experience various degrees of emotional, behavioral, sensory, learning, and social difficulties. In 1991, the gene responsible for FXS was identified on the X chromosome at q27.3 and named fragile x mental retardation 1 ( FMR1 ) gene.1 FXS and fragile X–associated disorders (FXD) are caused by a trinucleotide repeat (CGG) expansion mutation in the promoter region (exon 1) of FMR1 . Affected individuals with the full FXS mutation have >200 repeats. When the full mutation is present, FMR1 methylation occurs during gestation, which causes silencing of gene transcription.2 This in turn leads to a reduction or absence of fragile X mental retardation protein (FMRP), which is needed for brain development and function. Most males with FXS have ID. A small number of males have less impaired function due to methylation patterns or mosaicism. In females, FMRP levels depend on the X activation ratio, or the percent of cells expressing the normal allele on the active X chromosome,3 resulting in a range of normal intellectual ability to moderate ID.

Over the past 2 decades, scientists have made significant advancements in identifying and describing genetic, molecular, and cellular underpinnings of FXS, allowing for a more precise diagnosis of this condition. The present challenge is to move from accurate diagnosis to public health action for FXS, requiring better understanding of the natural history of FXS, … 

Address correspondence to Julie Bolen, PhD, MPH, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, 4770 Buford Hwy (E-88), Atlanta, GA 30341. E-mail: jcr2{at}cdc.gov
Influenza H3 hemagglutinin vaccine with scrambled immunodominant epitopes elicits antibodies directed toward immunosubdominant head epitopes (2023)

Vaccination is the most effective countermeasure to reduce the severity of influenza. Current seasonal influenza vaccines mainly elicit humoral immunity targeting hemagglutinin (HA). In particular, the amino acid residues around the receptor-binding site in the HA head domain are predominantly targeted by humoral immunity as "immunodominant" epitopes. However, mutations readily accumulate in the head domain due to high plasticity, resulting in antigenic drift and vaccine mismatch, particularly with influenza A (H3N2) viruses. A vaccine strategy that targets more conserved immunosubdominant epitopes is required to attain a universal vaccine. Here, we designed an H3 HA vaccine antigen with various amino acids at immunodominant epitopes of the HA head domain, termed scrambled HA (scrHA). In ferrets, scrHA vaccination induced lower serum neutralizing antibody levels against homologous virus compared with wild-type (WT) HA vaccination; however, similar levels of moderately neutralizing titers against antigenically distinct H3N2 viruses were observed. Ferrets vaccinated with scrHA twice and then challenged with homologous or heterologous virus showed the same level of reduced virus shedding in nasal swabs as WT HA-vaccinated animals but reduced body temperature increase, whereas WT HA-vaccinated ferrets exhibited body temperature increases similar to those of mock-vaccinated animals. scrHA elicited antibodies against HA immunodominant and -subdominant epitopes at lower and higher levels, respectively, than WT HA vaccination, whereas antistalk antibodies were induced at the same level for both groups, suggesting scrHA-induced redirection from immunodominant to immunosubdominant head epitopes. scrHA vaccination thus induced broader coverage than WT HA vaccination by diluting out the immunodominancy of HA head epitopes. IMPORTANCE Current influenza vaccines mainly elicit antibodies that target the immunodominant head domain, where strain-specific mutations rapidly accumulate, resulting in frequent antigenic drift and vaccine mismatch. Targeting conserved immunosubdominant epitopes is essential to attain a universal vaccine. Our findings with the scrHA developed in this study suggest that designing vaccine antigens that "dilute out" the immunodominancy of the head epitopes may be an effective strategy to induce conserved immunosubdominant epitope-based immune responses.
Experimental Mechanics for Multifunctional Composites and Next Generation UAVs (2017)

Low-cost unmanned aircraft that use affordable manufacturing and have limited service life can enable mission concepts in which there is a higher tolerance for aircraft loss, or attrition. Because of their higher risk tolerance, these low-cost attritable aircraft could also integrate emerging technology which may have previously been considered too risky for integration into expensive and long life aircraft. Light-weight multifunctional structural composites have the potential to integrate additional functions and enable mission agility without significantly adding weight or reducing payload capacity. However, design and development of these material systems are often difficult because of the traditional “building block” development approach used for traditional composites, the large option space available for structural and functional properties, and the potential complexity of the multiscale and multiphysics coupling. To realize integrated functionality, new multi-scales and multi-physical experimental mechanical characterization techniques should be merged with maturing integrated materials models. We discuss this need using examples of a reconfigurable liquid metal Structurally Embedded Vascular Antenna (SEVA), a plasmonic nanoparticle based method for measuring internal temperature gradients, and embedded micro-cantilever carbon-nanotube based sensors. The latter of these is also used to discuss the potential to accelerate development of multifunctional structural concepts by provide air flow measurement and structural feedback during testing of complex structures. This could, in turn, eliminate some testing of intermediate elements in the slow and expensive traditional “building block” approach.
Chirp reduction and on/off contrast enhancement via optical injection locking and coherent carrier manipulation (2013)

The most cost-effective solution for modulating data onto an optical carrier is via direct modulation of a semiconductor laser. Unfortunately, this approach suffers from high chirp. The chirp can be reduced by reducing the on/off modulation contrast ratio (i.e. by keeping the signaling laser well above threshold when generating both logical ‘0’ and ‘1’ bits), but the low contrast ratio itself compromises performance. Other techniques can better suppress chirp, e,g., based on selfinjection or optical injection locking of the directly-modulated laser (slave) to another laser (master) that emits CW light. However, this technique although very efficient at eliminating chirp, also requires the slave laser be operated well above threshold. We show however that the issue of the limited on/off modulation contrast can be addressed in this instance by subtraction of the carrier using a component of the master beam and an interferometric arrangement.
Evaluation of limb compartment with suspected increased interstitial pressure. A noninvasive method for determining quantitative hardness. (1994)

Six compartments in four dogs and three compartments in three anatomic specimen limbs were injected with plasma, and the intracompartmental interstitial pressure and hardness of the compartments were measured. Six patients suspected of having compartment syndromes were also studied. Of the compartments evaluated in the dog and anatomic specimen limbs, the average correlation coefficient between measurements with the two methods was 0.95 (range, 0.87 to 0.99). In six patients suspected of having compartment syndromes, the ratios of quantitative hardness of the injured to uninjured limbs closely matched the intracompartmental interstitial pressure measurement ratios (correlation coefficient, 0.95). All correlation coefficients were significant (F test, p < 0.05). There was a close correlation between the direct measurement of intracompartmental interstitial pressure with the wick catheter and quantitative hardness in compartment syndrome models in dog and anatomic specimen limbs, and in patients suspected of having compartment syndromes. The determination of surface hardness of limb compartments, which appears accurate and reproducible, offers the advantages of being noninvasive and well suited for longer-term assessments of intracompartmental interstitial pressure.
2A1-J21 Behavior Programming Course using Omnidirectional Mobile Robots with an Arm and a Camera : Case Study at the Dept. of Mechano-Informatics of The University of Tokyo (2008)

This paper describes a robot programming course for 3rd-grade undergraduate students at the department of mechano-informatics, the university of Tokyo. This course includes many issues for building a mobile robot's behavior programming: Programming in embedded Linux environment, image processing, inverse kinematics for an arm and an omnidirectional mobile robot, etc. These issues are integrated as mobile robot's behaviors where robots explore the environment using vision and other sensors and act on the environment using omnidirectional wheels and an arm.
Data from BRCA1-Interacting Protein OLA1 Requires Interaction with BARD1 to Regulate Centrosome Number (2023)

&lt;div&gt;Abstract&lt;p&gt;BRCA1 functions as a tumor suppressor in DNA repair and centrosome regulation. Previously, Obg-like ATPase 1 (OLA1) was shown to interact with BARD1, a heterodimer partner of BRCA1. OLA1 binds to BRCA1, BARD1, and γ-tubulin and functions in centrosome regulation. This study determined that overexpression of wild-type OLA1 (OLA1-WT) caused centrosome amplification due to centriole overduplication in mammary tissue–derived cells. Centrosome amplification induced by overexpression of the cancer-derived OLA1 mutant, which is deficient at regulating centrosome number, occurred in significantly fewer cells than in that induced by overexpression of OLA1-WT. Thus, it was hypothesized that overexpression of OLA1 with normal function efficiently induces centrosome amplification, but not that of OLA1 mutants, which are deficient at regulating centrosome number. We analyzed whether overexpression of OLA1 missense mutants of nine candidate phosphorylation residues, three residues modified with acetylation, and two ATP-binding residues caused centrosome amplification and identified five missense mutants that are deficient in the regulation of centrosome number. Three of them did not bind to BARD1. Two phosphomimetic mutations restored the binding to BARD1 and the efficient centrosome amplification by their overexpression. Knockdown and overexpression of BARD1 also caused centrosome amplification. BARD1 mutant reported in cancer failed to bind to OLA1 and rescue the BARD1 knockdown-induced centrosome amplification and reduced its centrosomal localization. Combined, these data reveal that the OLA1–BARD1 interaction is important for the regulation of centrosome number.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Implications:&lt;/b&gt; Regulation of centrosome number by BRCA1/BARD1 together with OLA1 is important for the genome integrity to prevent tumor development. &lt;i&gt;Mol Cancer Res; 16(10); 1499–511. ©2018 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Impact of Current Primary Biliary Cholangitis (PBC) Treatment Paradigms on Clinical, Health Related Quality of Life (HRQoL), and Cost-Effectiveness (CE) Outcomes: A Systematic Literature Review (SLR) (2017)

Introduction: PBC is a rare autoimmune, chronic liver disease that is associated with adverse health outcomes and reduced life expectancy. Symptoms of early PBC include pruritus and fatigue, with later stages manifesting complications of portal hypertension such as ascites, peripheral oedema and bleeding varices. Current treatment options include first-line ursodeoxycholic acid (UDCA), a naturally occurring bile acid, and recently-approved obeticholic acid (OCA), a farnesoid x receptor agonist, which is indicated in adults with an inadequate response or intolerance to UDCA. To estimate real world effectiveness (RWE) of a drug, it is important not only to assess clinical outcomes, but also estimate health resource utilization (HRU), costs, and HRQoL in the real-world environment. In this study, we performed a SLR to determine the RWE of currently available PBC treatments. Methods: A literature search (1995-2017) was conducted using Medline, Embase, Cochrane, National Health Service (NHS) Economic Evaluation and NHS Health Technology Assessment Databases. The English-language studies were systematically reviewed to assess the impact of current treatment paradigms on clinical, economic and humanistic outcomes in patients with PBC. Results: 102 journal articles out of 2936 initial hits were included; 77 studies exploring treatment effects on disease biomarker/clinical endpoints were used to elucidate the natural history of PBC and the impact of early interventions on slowing disease progression. 3 of 5 studies assessing patient perspective [patient reported outcomes (PROs)] showed that fatigue had a major impact by impairing patients' HRQoL. However, studies examining treatment effects on HRQoL showed mixed results. Studies collecting PBC-related HRU and costs were nonexistent. Two CE analyses evaluating UDCA monotherapy vs no treatment showed cost savings and increased life expectancy in treated patients; a third study comparing use of OCA as a 2nd line treatment vs placebo used key inputs and assumptions based on HepC related liver disease, and concluded that OCA was not CE based on a threshold for willingness to pay. Conclusion: This SLR documents a tremendous paucity of data and the need for a more accurate understanding of the true medical value of PBC and its treatments. Future research should include standardized measures of the comprehensive outcomes for PBC such as clinical endpoints, PROs, health utilities and PBC-specific HRU.
Donor Toll-like receptor 4 contributes to ischemia and reperfusion injury following human kidney transplantation (2009)

While studies in animal models have linked Toll-like receptor (TLR) 4 signaling to kidney injury induced by ischemia and reperfusion, the relevance of TLR4 activation to allograft injury in human kidney transplants is unknown. Here we show that TLR4 is constitutively expressed within all donor kidneys but is significantly higher in deceased-, compared with living-donor organs. Tubules from deceased- but not living-donor kidneys also stained positively for high-mobility group box-1 (HMGB1), a known endogenous TLR4 ligand. In vitro stimulation of human tubular cells with HMGB1, in a TLR4-dependent system, confirmed that HMGB1 can stimulate proinflammatory responses through TLR4. To assess the functional significance of TLR4 in human kidney transplantation, we determined whether TLR4 mutations that confer diminished affinity for HMGB1 influence intragraft gene-expression profiles and immediate graft function. Compared with kidneys expressing WT alleles, kidneys with a TLR4 loss-of-function allele contained less TNFalpha, MCP-1, and more heme oxygenase 1 (HO-1), and exhibited a higher rate of immediate graft function. These results represent previously undetected evidence that donor TLR4 contributes to graft inflammation and sterile injury following cold preservation and transplantation in humans. Targeting TLR4 signaling may have value in preventing or treating postischemic acute kidney injury after transplantation.
Preparation of Tripodal Vanadium Oxo-Organometallic Species Supported on Silica, [(≡SiO)<sub>3</sub>V(═O)], for Selective Nonoxidative Dehydrogenation of Propane (2022)

In this work, a strategy based on the grafting of a vanadium molecular complex, [V(═O)(OtBu)3], (1), bearing tert-butoxide ligands, on a partially dehydroxylated silica, followed by a thermal treatment has been used for the preparation of supported tripodal V oxo complex, [(≡SiO)3V(═O)], active species, for important chemical processes. The molecular complex reacts with a silica partially dehydroxylated at 200 °C (SiO2–200) to lead to bipodal [(≡SiO)2V(═O)(OtBu)] (2) as major surface species, while monopodal surface species [(≡SiO)V(═O)(OtBu)2] (3) are obtained on SiO2–700. These materials were thermally treated to form active supported tripodal vanadium oxo species by releasing isobutene via a β-H transfer, leading to V–OH intermediate. The latter species lead to the targeted tripodal oxo species [(≡SiO)3V(═O)] after restructuration of the support and will be represented as materials (2a) and (3a). All of the supported vanadium complexes were characterized by diffuse reflectance infrared Fourier transform (DRIFT), UV–vis, solid-state NMR, and X-ray absorption near edge structure (XANES) spectroscopies. In particular, the structure of isolated vanadium oxo tripodal species, [(≡SiO)3V(═O)], was confirmed by 51V NMR with a major peak at −670 ppm, as reported in the literature. The catalytic property of (2a) and (3a) was evaluated for the direct propane dehydrogenation and showed promising performances that can be solely assigned to the isolated vanadium tripodal species.