gebhart/patrepeval huggingface dataset:
Dissection of the two transferase activities of the Pasteurella multocida hyaluronan synthase: two active sites exist in one polypeptide (2000)

Type A Pasteurella multocida, an animal pathogen, employs a hyaluronan [HA] capsule to avoid host defenses. PmHAS, the 972-residue membrane-associated hyaluronan synthase, catalyzes the transfer of both GlcNAc and GlcUA to form the HA polymer. To define the catalytic and membrane-associated domains, pmHAS mutants were analyzed. PmHAS1-703 is a soluble, active HA synthase suggesting that the carboxyl-terminus is involved in membrane association of the native enzyme. PmHAS1-650 is inactive as a HA synthase, but retains GlcNAc-transferase activity. Within the pmHAS sequence, there is a duplicated domain containing a short motif, Asp-Gly-Ser, that is conserved among many beta-glycosyltransferases. Changing this aspartate in either domain to asparagine, glutamate, or lysine reduced the HA synthase activity to low levels. The mutants substituted at residue 196 possessed GlcUA-transferase activity while those substituted at residue 477 possessed GlcNAc-transferase activity. The Michaelis constants of the functional transferase activity of the various mutants, a measure of the apparent affinity of the enzymes for the precursors, were similar to wild-type values. Furthermore, mixing D196N and D477K mutant proteins in the same reaction allowed HA polymerization at levels similar to the wild-type enzyme. These results provide the first direct evidence that the synthase polypeptide utilizes two separate glycosyltransferase sites.
Mycoplasma pneumoniae in children (2014)

The current diagnostic procedures for M. pneumoniae cannot discern between bacterial carriage and infection in a clinically relevant time frame. It is therefore imperative that these procedures be modified such as to unambiguously detect symptomatic M. pneumoniae infections. Moreover, the emergence of MRMP necessitates the application of methods to detect macrolide resistance as well as the implementation of restrictive policies regarding the use of macrolides.
Molecular Cloning of Polyoma Virus DNA in Escherichia coli : Lambda Phage Vector System (1979)

The biological activity of recombinant phage and recombinant phage DNA containing monomeric or dimeric polyoma DNA inserts was examined in mice and cultured mouse cells. Recombinant preparations containing a single copy of viral DNA were invariably noninfectious; molecules containing a dimeric polyoma DNA insert were at least seven orders of magnitude less infectious than polyoma virions after parenteral inoculation. No infection was detected with any recombinant preparation after oral administration.
Comparative promoter analysis in vivo: identification of a dendritic cell-specific promoter module (2011)

Dendritic cells (DCs) are important immune cells. This study focused on transcriptional networks active in murine DCs, but DCs are difficult to study using conventional molecular techniques. Therefore, comparative promoter analysis was used to identify evolutionarily conserved features between the murine CD11c and DC-STAMP promoters. A promoter framework consisting of 4 transcription factor binding sites was identified that included signal transducer and activator of transcription, homeodomain transcription factors, and 2 members of the Brn POU domain factors family. This promoter module was functionally verified by in vivo promoter analysis and site-directed mutagenesis. Hematopoietic stem cells were engineered by lentiviral vectors and expression of green fluorescent protein reporter was monitored in primary hematopoietic cell types that develop without further manipulation in irradiated recipient mice. The verified promoter module was then modeled and used in a bioinformatics-based search for other potential coregulated genes in murine DCs. A promoter database search identified 2 additional genes, Ppef2 and Pftk1, which have a similar promoter organization and are preferentially expressed in murine DCs. The results define a regulatory network linked to development of murine DCs.
Real-Time Label-Free Direct Electronic Monitoring of Topoisomerase Enzyme Binding Kinetics on Graphene (2015)

Monolayer graphene field-effect sensors operating in liquid have been widely deployed for detecting a range of analyte species often under equilibrium conditions. Here we report on the real-time detection of the binding kinetics of the essential human enzyme, topoisomerase I interacting with substrate molecules (DNA probes) that are immobilized electrochemically on to monolayer graphene strips. By monitoring the field-effect characteristics of the graphene biosensor in real-time during the enzyme-substrate interactions, we are able to decipher the surface binding constant for the cleavage reaction step of topoisomerase I activity in a label-free manner. Moreover, an appropriate design of the capture probes allows us to distinctly follow the cleavage step of topoisomerase I functioning in real-time down to picomolar concentrations. The presented results are promising for future rapid screening of drugs that are being evaluated for regulating enzyme activity.
Superior flux pinning in in situ synthesized silver-sheathed superconducting tape of Tl0.5Pb0.5Sr1.6Ba0.4Ca0.8Y0.2Cu2Oy (1993)

In situ synthesis has been developed for the first time to fabricate the Tl-based silver-sheathed superconducting tapes. Tapes of Tl0.5Pb0.5Sr1.6Ba0.4Ca0.8Y0.2Cu2Oy (Tl-1212) made by the in situ synthesis method under optimal oxygen partial pressure were found to have transport Jc of 7000 A/cm2 in the absence of external magnetic field. In low magnetic field (&amp;lt;0.2 T) the Jc decreases rapidly with field due to weak links. But the Tl-1212 tapes exhibited flux-pinning properties superior to those of Tl-1223 tapes when measured by SQUID at 77 K. XRD pattern of the powdered superconducting material shows it to be a single 1212 phase. Both transport measurement by the four-probe method and magnetization measurement by SQUID also show that it is a single phase with zero resistance and onset transition temperatures of 97.5–99.0 and 101–103 K, respectively, under a measuring current of 150 mA.
Androgen-independent prostate cancer progression in the TRAMP model. (1997)

We previously established the autochthonous transgenic adenocarcinoma mouse prostate (TRAMP) model to facilitate characterization of molecular mechanisms involved in the initiation and progression of prostate cancer. TRAMP mice display high grade prostatic intraepithelial neoplasia or well-differentiated prostate cancer by 10-12 weeks of age. To test the hypothesis that molecular events leading to androgen independence and metastasis can occur early in the natural history of prostate cancer yet remain silent until selective pressures such as androgen deprivation are applied, we have examined the consequences of castration on the initiation and progression to metastatic prostate cancer in TRAMP mice. Cohorts were castrated at 12 weeks of age and sacrificed at 18 (T12/18) or 24 (T12/24) weeks of age, and the development of primary cancer and metastatic disease was compared to noncastrated (T18 and T24) controls. Median T12/18 and T12/24 genitourinary (GU) weight was significantly less than T18 and T24, respectively. In addition, T12/24 GU weight was significantly greater than T12/18. Histological prostate tumors developed in 3 of 7 T12/18 and 8 of 10 T12/24 mice. All tumors that developed in castrated mice were poorly differentiated in contrast to 27% in noncastrated controls. Although castration significantly decreased GU tumor burden, overall progression to poorly differentiated and metastatic disease was not ultimately delayed. These results demonstrate that prostate cancer in the TRAMP model is heterogeneous with respect to androgen dependence as early as 12 weeks of age; therefore, early androgen ablation may have a variable impact on progression in an individual mouse. Further analysis of this prostate cancer model to identify specific molecular mechanisms that determine androgen sensitivity may facilitate future initiation of appropriate individualized hormonal therapy for the management of human prostate cancer.
Conserved Structures Exposed in HIV-1 Envelope Glycoproteins Stabilized by Flexible Linkers as Potent Entry Inhibitors and Potential Immunogens (2002)

The HIV-1 envelope glycoprotein (Env) undergoes conformational changes while driving entry. We hypothesized that some of the intermediate Env conformations could be represented in tethered constructs where gp120 and the ectodomain of gp41 are joined by flexible linkers. Tethered Envs with long linkers (gp140-14 with 15 aa and gp140-24 with 26 aa) were stable and recognized by conformationally dependent anti-gp120 and anti-gp41 monoclonal antibodies (mAbs). Surprisingly, these proteins potently inhibited membrane fusion mediated by R5, X4, and R5X4 Envs with 5-100-fold lower IC50 than a tethered Env with short linker (gp140-4 with 4 aa), gp120, gp140, soluble CD4, or DP178 (T20). Compared to gp140, gp140-14,24 exhibited increased binding to anti-gp41 cluster II mAbs but not to cluster I mAbs. Cluster II mAbs but not cluster I, IV, or V mAbs reversed the inhibitory effect of gp140-14,24 suggesting a role of exposed conserved gp41 structures for the mechanism of inhibition. These findings suggest the existence of conserved gp41 structures that are important for HIV-1 entry and can be stably exposed in the native environment of the Env even in the absence of receptor-mediated activation. Thus, tethered Envs with long linkers may not only be important as HIV-1 inhibitors but also for elucidation of viral entry mechanisms and development of novel vaccine immunogens.
Flipping Yeast (1996)

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Catalytic utilization of eIF-2 and mRNA binding proteins are limiting in lysates from vesicular stomatitis virus infected L cells (1984)

Infection of mouse L cells by vesicular stomatitis virus results in the inhibition of cellular protein synthesis. Lysates prepared from these infected cells are impaired in their ability to translate endogenous or exogenous cellular and viral mRNAs. The ability of initiation factors from rabbit reticulocytes to stimulate protein synthesis in these lysates was examined. Preparations of eukaryotic initiation factor 2 (eIF-2) and the guanine nucleotide exchange factor (GEF) stimulated protein synthesis strongly in L cell lysates from infected cells but only slightly in lysates from mock-infected cells. Maximal stimulation was obtained when a fraction containing eukaryotic initiation factors 4B (eIF-4B) and 4F (eIF-4F) was also present. In lysates from infected cells, these initiation factors increased endogenous cellular mRNA translation on the average 2-fold. In contrast, endogenous viral mRNA translation was increased to a much greater extent: the M protein was stimulated 8-fold, NS 5-fold, N 2.5-fold, and G 12-fold. When fractions containing eIF-4B, eIF-4F, or eIF-4A were added to these lysates in the presence of eIF-2, all three stimulated translation. Fractions containing rabbit reticulocyte initiation factors eIF-3 and eIF-6 had no effect on translation in either lysate. The results suggest that lysates from infected L cells are defective in the catalytic utilization of eIF-2 and deficient in mRNA binding protein activity.
File system performance and transaction support (1992)

This thesis considers two related issues: the impact of disk layout on file system throughput and the integration of transaction support in file systems. &lt;p&gt;Historic file system designs have optimized for reading, as read throughput was the I/O performance bottleneck. Since increasing main-memory cache sizes effectively reduce disk read traffic, disk write performance has become the I/O performance bottleneck. This thesis presents both simulation and implementation analysis of the performance of read-optimized and write-optimized file systems. &lt;p&gt;An example of a file system with a disk layout optimized for writing is a log-structured file system, where writes are bundled and written sequentially. Empirical evidence in [ROSE90], [ROSE91], and [ROSE92] indicates that a log-structured file system provides superior write performance and equivalent read performance to traditional file systems. This thesis analyzes and evaluates the log-structured file system presented in [ROSE91], isolating some of the critical issues in its design. Additionally, a modified design addressing these issues is presented and evaluated. &lt;p&gt;Log-structured file systems also offer the potential for superior integration of transaction processing into the system. Because log-structured file systems use logging techniques to store files, incorporating transaction mechanisms into the file system is a natural extension. This thesis presents the design, implementation, and analysis of both user-level transaction management on read and write optimized file systems and embedded transaction management in a write optimized file system. &lt;p&gt;This thesis shows that both log-structured file systems and simple, read-optimized file systems can attain nearly 100% of the disk bandwidth when I/Os are large or sequential. The improved write performance of LFS discussed in [ROSE92] is only attainable when garbage collection overhead is small, and in nearly all of the workloads examined, performance of LFS is comparable to that of a read-optimized file system. On transaction processsing workloads where a steady stream of small, random I/Os are issued, garbage collection reduces LFS throughput by 35% to 40%
PHOTOCHEMISTRY IN TERRESTRIAL EXOPLANET ATMOSPHERES. I. PHOTOCHEMISTRY MODEL AND BENCHMARK CASES (2012)

We present a comprehensive photochemistry model for exploration of the chemical composition of terrestrial exoplanet atmospheres. The photochemistry model is designed from the ground up to have the capacity to treat all types of terrestrial planet atmospheres, ranging from oxidizing through reducing, which makes the code suitable for applications for the wide range of anticipated terrestrial exoplanet compositions. The one-dimensional chemical transport model treats up to 800 chemical reactions, photochemical processes, dry and wet deposition, surface emission and thermal escape of O, H, C, N and S bearing species, as well as formation and deposition of elemental sulfur and sulfuric acid aerosols. We validate the model by computing the atmospheric composition of current Earth and Mars and find agreement with observations of major trace gases in Earth's and Mars' atmospheres. We simulate several plausible atmospheric scenarios of terrestrial exoplanets, and choose three benchmark cases for atmospheres from reducing to oxidizing. The most interesting finding is that atomic hydrogen is always a more abundant reactive radical than the hydroxyl radical in anoxic atmospheres. Whether atomic hydrogen is the most important removal path for a molecule of interest also depends on the relevant reaction rates. We also find that volcanic carbon compounds (i.e., CH4 and CO2) are chemically long-lived and tend to be well mixed in both reducing and oxidizing atmospheres, and their dry deposition velocities to the surface control the atmospheric oxidation states. Furthermore, we revisit whether photochemically produced oxygen can cause false positives for detecting oxygenic photosynthesis, and find that in 1-bar CO2-rich atmospheres oxygen and ozone may build up to levels that have been previously considered unique signatures of life, if there is no surface emission of reducing gases...
Calibration of a structured light system: a projective approach (2002)

We present in this paper a novel calibration method that uses cross ratio to compute world points falling onto any given light stripe plane of a structured light system. We show that, by using 4 known non-coplanar sets of 3 collinear world points, the direct 4/spl times/3 image-to-world transformation matrix for each light stripe plane can also be recovered from plane-to-plane homography. Preliminary experiments conducted with a calibration target and a mannequin suggest that this novel calibration method is robust and is applicable to many shape measurement task.
Compact Planar Monopole Antenna for Multi-band Mobile Phones (2006)

A novel planar monopole antenna suitable for mobile handset applications is presented in this paper. The antenna is mainly composed of a rectangular radiating patch with a meandered slot on, and due to the slot three branches are constructed, two resonating branches and a tuning one. The antenna is printed on an FR4 substrate and fed by a 50/spl Omega/ microstrip line. A prototype has been fabricated and studied. The resulting antenna is able to operate in the GSM, DCS, PCS, UMTS and WLAN bands with a voltage standing wave ratio (VSWR) better than 2.5. Both simulated and measured results are presented.
Infection Prevention and Control in Deployed Military Medical Treatment Facilities (2011)

Infections have complicated the care of combat casualties throughout history and were at one time considered part of the natural history of combat trauma. Personnel who survived to reach medical care were expected to develop and possibly succumb to infections during their care in military hospitals. Initial care of war wounds continues to focus on rapid surgical care with debridement and irrigation, aimed at preventing local infection and sepsis with bacteria from the environment (e.g., clostridial gangrene) or the casualty's own flora. Over the past 150 years, with the revelation that pathogens can be spread from patient to patient and from healthcare providers to patients (including via unwashed hands of healthcare workers, the hospital environment and fomites), a focus on infection prevention and control aimed at decreasing transmission of pathogens and prevention of these infections has developed. Infections associated with combat-related injuries in the recent operations in Iraq and Afghanistan have predominantly been secondary to multidrug-resistant pathogens, likely acquired within the military healthcare system. These healthcare-associated infections seem to originate throughout the system, from deployed medical treatment facilities through the chain of care outside of the combat zone. Emphasis on infection prevention and control, including hand hygiene, isolation, cohorting, and antibiotic control measures, in deployed medical treatment facilities is essential to reducing these healthcare-associated infections. This review was produced to support the Guidelines for the Prevention of Infections Associated With Combat-Related Injuries: 2011 Update contained in this supplement of Journal of Trauma.
Crystal Structure of a Recombinant Anti-estradiol Fab Fragment in Complex with 17β-Estradiol (2001)

The crystal structure of a Fab fragment of an anti-17beta-estradiol antibody 57-2 was determined in the absence and presence of the steroid ligand, 17beta-estradiol (E2), at 2.5 and 2.15-A resolutions, respectively. The antibody binds the steroid in a deep hydrophobic pocket formed at the interface between the variable domains. No major structural rearrangements take place upon ligand binding; however, a large part of the heavy chain variable domain near the binding pocket is unusually flexible and is partly stabilized when the steroid is bound. The nonpolar steroid skeleton of E2 is recognized by a number of hydrophobic interactions, whereas the two hydroxyl groups of E2 are hydrogen-bonded to the protein. Especially, the 17-hydroxyl group of E2 is recognized by an intricate hydrogen bonding network in which the 17-hydroxyl itself forms a rare four-center hydrogen bond with three polar amino acids; this hydrogen bonding arrangement accounts for the low cross-reactivity of the antibody with other estrogens such as estrone. The CDRH3 loop plays a prominent role in ligand binding. All the complementarity-determining regions of the light chain make direct contacts with the steroid, even CDRL2, which is rarely directly involved in the binding of haptens.
Losartan prevents acquired epilepsy via TGF‐β signaling suppression (2014)

TGF-β signaling, activated in astrocytes by serum-derived albumin, is involved in epileptogenesis. We propose losartan, a drug approved by the US Food and Drug Administration, as an efficient antiepileptogenic therapy for epilepsy associated with vascular injury.
Synthesis of Antiproliferative Cephalotaxus Esters and Their Evaluation against Several Human Hematopoietic and Solid Tumor Cell Lines: Uncovering Differential Susceptibilities to Multidrug Resistance (2008)

Deoxyharringtonine (2), homoharringtonine (3), homodeoxyharringtonine (4), and anhydroharringtonine (5) are reported to be among the most potent members of the antileukemia alkaloids isolated from the Cephalotaxus genus. Convergent syntheses of these four natural products are described, each involving novel synthetic methods and strategies. These syntheses enabled evaluation of several advanced natural and non-natural compounds against an array of human hematopoietic and solid tumor cells. Potent cytotoxicity was observed in several cell lines previously not challenged with these alkaloids. Variations in the structure of the ester chain within this family of alkaloids confer differing activity profiles against vincristine-resistant HL-60/RV+, signalling new avenues for molecular design of these natural products to combat multi-drug resistance.
Review of Neural Networks for Speech Recognition (1989)

The performance of current speech recognition systems is far below that of humans. Neural nets offer the potential of providing massive parallelism, adaptation, and new algorithmic approaches to problems in speech recognition. Initial studies have demonstrated that multilayer networks with time delays can provide excellent discrimination between small sets of pre-segmented difficult-to-discriminate words, consonants, and vowels. Performance for these small vocabularies has often exceeded that of more conventional approaches. Physiological front ends have provided improved recognition accuracy in noise and a cochlea filter-bank that could be used in these front ends has been implemented using micro-power analog VLSI techniques. Techniques have been developed to scale networks up in size to handle larger vocabularies, to reduce training time, and to train nets with recurrent connections. Multilayer perceptron classifiers are being integrated into conventional continuous-speech recognizers. Neural net architectures have been developed to perform the computations required by vector quantizers, static pattern classifiers, and the Viterbi decoding algorithm. Further work is necessary for large-vocabulary continuous-speech problems, to develop training algorithms that progressively build internal word models, and to develop compact VLSI neural net hardware.
Covalent Display of Oligosaccharide Arrays in Microtiter Plates (2004)

A covalent array for the display of complex oligosaccharides in microtiter plates has been developed. This strategy is conducive to the display of carbohydrates to proteins of interest such as lectins and antibodies, including the broadly neutralizing antibody 2G12 against HIV envelope oligomannose and can be cleaved from the surface for further characterization by mass spectrometry. The system was used to probe the multivalent interaction of 2G12 with an optimal epitope (Kd 0.1 muM).