gebhart/patrepeval huggingface dataset:
Cloning and expression in Escherichia coli of the Alcaligenes eutrophus H16 poly-beta-hydroxybutyrate biosynthetic pathway (1988)

The poly-beta-hydroxybutyrate (PHB) biosynthetic pathway from Alcaligenes eutrophus H16 has been cloned and expressed in Escherichia coli. Initially, an A. eutrophus H16 genomic library was constructed by using cosmid pVK102, and cosmid clones that encoded the PHB biosynthetic pathway were sought by assaying for the first enzyme of the pathway, beta-ketothiolase. Six enzyme-positive clones were identified. Three of these clones manifested acetoacetyl coenzyme A reductase activity, the second enzyme of the biosynthetic pathway, and accumulated PHB. PHB was produced in the cosmid clones at approximately 50% of the level found in A. eutrophus. One cosmid clone was subjected to subcloning experiments, and the PHB biosynthetic pathway was isolated on a 5.2-kilobase KpnI-EcoRI fragment. This fragment, when cloned into small multicopy vectors, can direct the synthesis of PHB in E. coli to levels approaching 80% of the bacterial cell dry weight.
Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema (2015)

Intravitreous aflibercept, bevacizumab, or ranibizumab improved vision in eyes with center-involved diabetic macular edema, but the relative effect depended on baseline visual acuity. When the initial visual-acuity loss was mild, there were no apparent differences, on average, among study groups. At worse levels of initial visual acuity, aflibercept was more effective at improving vision. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01627249.).
Wide-angle nonmechanical beam steering using thin liquid crystal polarization gratings (2008)

We introduce and demonstrate a compact, nonmechanical beam steering device based on liquid Crystal (LC) Polarization Gratings (PGs). Directional control of collimated light is essential for free-space optical communications, remote sensing, and related technologies. However, current beam steering methods often require moving parts, or are limited to small angle operation, offer low optical throughput, and are constrained by size and weight. We employ multiple layers of LCPGs to achieve wide-angle (> &plusmn;40&deg;), coarse beam steering of 1550 nm light in a remarkably thin package. LCPGs can be made in switchable or polymer materials, and possess a continuous periodic birefringence profile, that renders several compelling properties (experimentally realized): ~ 100% experimental diffraction efficiency into a single order, high polarization sensitivity, and very low scattering. Light may be controlled within and between the zero- and first-diffraction orders by the handedness of the incident light and potentially by voltage applied to the PG itself. We implement a coarse steering device with several LCPGs matched with active halfwave LC variable retarders. Here, we present the preliminary experimental results and discuss the unique capability of this wide-angle steering.
Overexpression ofhnsin the plant growth-promoting bacteriumEnterobacter cloacaeUW5 increases root colonization (2009)

A better understanding of the genes involved in plant colonization will contribute to the development of PGPR that can compete more effectively in agricultural soils.
Implication of macrophages in tumor rejection induced by CpG-oligodeoxynucleotides without antigen. (2001)

Phosphorothioate oligodeoxynucleotides containing CpG motifs (CpG-ODNs) display broad immunostimulating activity and have potential applications in cancer immunotherapy. To investigate the antitumor activity of CpG-ODNs and to study the role of macrophages and lymphocytes in tumor rejection, CpG-ODN's effects on 9 L glioma cells were assessed in Fisher rats, depleted or not in macrophages, in nude mice, and in SCID mice. In nondepleted rats, intratumoral injections with 100 microg of CpG-ODNs on days 5, 12, and 19, after s.c. 9 L cell inoculations, resulted in an 84% reduction of the tumor volumes, when compared with controls injected with saline (P < 0.0001). Whereas all control animals developed tumors, more than one-third of the treated rats remained tumor free. Rejection of established glioma induced a specific long-term immunity, as cured rats were protected against a subsequent 9 L injection, but not a RG2 cell inoculation, another syngenic glioma in Fischer rats. Macrophages played a critical role in the early phase of tumor rejection, because the CpG-ODN's effects were significantly decreased in the rats depleted in macrophages, and none of the macrophage-depleted rats treated with CpG-ODNs rejected the tumor. On the contrary, both nude and SCID mice, which have normal innate immunity, showed a significant decrease of tumor volume when treated with CpG-ODNs when compared with controls. T cells were however involved in a later phase of the tumor rejection, as all nude mice eventually developed tumors despite the initial tumor growth inhibition. Altogether, these data suggest that immunostimulatory CpG-ODNs induced tumor rejections through an early activation of innate immunity and priming of a specific immune response against glioma cells.
Escherichia coli serotyping and disease in man and animals (1992)

Serotyping of Escherichia coli is useful, but complex, with 173 O antigens, 80 K antigens, and 56 H antigens, which can all be subdivided into partial antigens. The O, K, and H antigens can be found in nature in many of the possible combinations. The final number of E. coli serotypes is very high, 50,000-100,000 or more. The number of frequent pathogenic serotypes is, however, limited. Two main groups of such frequent serotypes are (i) serotypes from diarrhoeal disease and (ii) serotypes from extraintestinal disease. Serotypes from diarrhoeal diseases are mostly species specific, and could at present be used as epidemiological markers for bacterial clones equipped with special virulence markers, such as toxins and adhesins. Their O-antigen lipopolysaccharides may be regarded as virulence factors. These strains are not inhabitants of the normal intestine. Serotypes from extraintestinal diseases constitute a different set of clones, which are good colonizers of the intestinal tract, that under certain conditions succeed in invading host tissues. They are characterized by virulence factors different from those found in strains from diarrhoeal disease. Thus, the two groups of pathogenic E. coli are both composed of a limited number of clones for which the O:K:H serotypes are excellent, although not faultless, markers.
Efficacy and Safety of Monoclonal Antibody to Human Tumor Necrosis Factor α in Patients With Sepsis Syndrome (1995)

<h3>Objective.</h3> —To evaluate the efficacy and safety of anti—tumor necrosis factor α monoclonal antibody (TNF-α MAb) in the treatment of patients with sepsis syndrome. <h3>Design.</h3> —Randomized, prospective, multicenter, double-blind, placebo-controlled clinical trial. <h3>Setting.</h3> —A total of 31 hospitals in the United States and Canada. <h3>Patients.</h3> —There were 994 patients with sepsis syndrome enrolled in this clinical trial, and 971 patients were infused with the study drug. <h3>Intervention.</h3> —Patients were prospectively stratified into shock or nonshock groups and then randomized to receive a single infusion of 15 mg/kg of TNF-α MAb, 7.5 mg/kg of TNF-α MAb, or placebo. Patients received standard aggressive medical and surgical care during the 28-day postinfusion period. <h3>Outcome Measure.</h3> —Twenty-eight-day all-cause mortality. <h3>Results.</h3> —The distribution of variables describing demographics, organ system dysfunction or failure, preinfusion Acute Physiology and Chronic Health Evaluation II score, number of organs failing at baseline, initial sites of infection, infecting microorganisms, antimicrobials used, and initial invasive procedures was similar among patients in the TNF-α MAb and placebo treatment arms. Among all infused patients, there was no difference in all-cause mortality in patients who received placebo as compared with those who received TNF-α MAb. In septic patients with shock (n=478), there was a trend toward a reduction in all-cause mortality, which was most evident 3 days after infusion: 25 of 162 patients treated with 15 mg/kg of TNF-α MAb died, 22 of 156 patients treated with 7.5 mg/kg of TNF-α MAb died, and 44 of 160 patients in the placebo group died (15 mg/kg: 44% reduction vs placebo,<i>P</i>=.01; 7.5 mg/kg: 48.7% reduction vs placebo,<i>P</i>=.004). At day 28, the reduction in mortality for shock patients was not significant for either dose of TNF-α MAb relative to placebo (15 mg/kg, 61 deaths among 162 patients [37.7% mortality]; 7.5 mg/kg, 59 deaths among 156 patients [37.8% mortality]; placebo, 73 deaths among 160 patients [45.6% mortality];<i>P</i>=.20 for 7.5 mg/kg and<i>P</i>=.15 for 15 mg/kg). Serious adverse events were reported in 4.6% of all infused patients. No immediate hypersensitivity allergic reactions due to TNF-α MAb were reported. Serum sickness—like reactions were seen in 2.5% of patients receiving TNF-α MAb. <h3>Conclusions.</h3> —There was no decrease in mortality between placebo and TNF-α MAb in all infused patients. In septic shock patients who received TNF-α MAb, a significant reduction in mortality was present 3 days after infusion. Although a trend toward reduced mortality continued at 28 days following treatment with TNF-α MAb, the difference in mortality among shock patients treated with placebo or TNF-α MAb was not significant. (<i>JAMA</i>. 1995;273:934-941)
CD40: A Pivotal Receptor In the Determination of Life/Death Decisions in B Lymphocytes (1997)

CD40 is a 48 kDa glycoprotein predominantly expressed on B cells in both mouse and man, which interacts with a counterligand (CD40L), expressed on activated CD4+ T cells. CD40/CD40L interactions are now known to be essential for the initiation of antibody responses to T-dependent antigens. In this review we discuss the immunobiology of CD40, with a special emphasis on our own studies in the mouse. These have focused on signal transduction via CD40, the role of cytokines (both T cell-derived and B cell-derived) in CD40-mediated B cell activation, and the role of CD40 in protecting B cells from apoptotic cell death. The available data indicate clearly that this protein is a pivotal receptor on B cells, both for the delivery of activating signals and for promoting B cell survival.
Atelocollagen‐Mediated Systemic DDS for Nucleic Acid Medicines (2006)

The goal of our research is to provide a practical platform for drug delivery in oligonucleotide therapy. We report here the efficacy of an atelocollagen-mediated oligonucleotide delivery system applied to systemic siRNA and antisense oligonucleotide treatments in animal disease models. Atelocollagen and oligonucleotides formed a complex of nanosized particles, which was highly stable against nucleases. The complex allowed oligonucleotides to be delivered efficiently into several organs and tissues via intravenous administration. In a tumor metastasis model, the complex successfully delivered siRNA to metastasized tumors in bone tissue and inhibited their growth. We also demonstrated that a single intravenous treatment of the antisense oligodeoxynucleotide complex suppressed ear dermatitis in a contact hypersensitivity model. These results indicate the strong potential of the atelocollagen-mediated drug delivery system for practical therapeutic technology.
Synchronous gestures for multiple persons and computers (2003)

This research explores distributed sensing techniques for mobile devices using synchronous gestures. These are patterns of activity, contributed by multiple users (or one user with multiple devices), which take on a new meaning when they occur together in time, or in a specific sequence in time. To explore this new area of inquiry, this work uses tablet computers augmented with touch sensors and two-axis linear accelerometers (tilt sensors). The devices are connected via an 802.11 wireless network and synchronize their time-stamped sensor data. This paper describes a few practical examples of interaction techniques using synchronous gestures such as dynamically tiling together displays by physically bumping them together, discusses implementation issues, and speculates on further possibilities for synchronous gestures.
Three-dimensional micro-channel fabrication in polydimethylsiloxane (PDMS) elastomer (2000)

This paper describes a fabrication technique for building three-dimensional (3-D) micro-channels in polydimethylsiloxane (PDMS) elastomer. The process allows for the stacking of many thin (less than 100-/spl mu/m thick) patterned PDMS layers to realize complex 3-D channel paths. The master for each layer is formed on a silicon wafer using an epoxy-based photoresist (SU 8). PDMS is cast against the master producing molded layers containing channels and openings. To realize thin layers with openings, a sandwich molding configuration was developed that allows precise control of the PDMS thickness. The master wafer is clamped within a sandwich that includes flat aluminum plates, a flexible polyester film layer, a rigid Pyrex wafer, and a rubber sheet. A parametric study is performed on PDMS surface activation in a reactive-ion-etching system and the subsequent methanol treatment for bonding and aligning very thin individual components to a substrate. Low RF power and short treatment times are better than high RF power and long treatment times, respectively, for instant bonding. Layer-to-layer alignment of less then 15 /spl mu/m is achieved with manual alignment techniques that utilize surface tension driven self-alignment methods. A coring procedure is used to realize off-chip fluidic connections via the bottom PDMS layer, allowing the top layer to remain smooth and flat for complete optical access.
Chipping Resistance of Graded Zirconia Ceramics for Dental Crowns (2012)

A serious drawback of veneering porcelains is a pronounced susceptibility to chipping. Glass-infiltrated dense zirconia structures can now be produced with esthetic quality, making them an attractive alternative. In this study, we examined the hypothesis that such infiltrated structures are much more chip-resistant than conventional porcelains, and at least as chip-resistant as non-infiltrated zirconia. A sharp indenter was used to produce chips in flat and anatomically correct glass-infiltrated zirconia crown materials, and critical loads were measured as a function of distance from the specimen edge (flat) or side wall (crown). Control data were obtained on zirconia specimens without infiltration and on crowns veneered with porcelains. The results confirmed that the resistance to chipping in graded zirconia is more than 4 times higher than that of porcelain-veneered zirconia and is at least as high as that of non-veneered zirconia.
Deep Structured Energy Based Models for Anomaly Detection (2016)

In this paper, we attack the anomaly detection problem by directly modeling the data distribution with deep architectures. We propose deep structured energy based models (DSEBMs), where the energy function is the output of a deterministic deep neural network with structure. We develop novel model architectures to integrate EBMs with different types of data such as static data, sequential data, and spatial data, and apply appropriate model architectures to adapt to the data structure. Our training algorithm is built upon the recent development of score matching \cite{sm}, which connects an EBM with a regularized autoencoder, eliminating the need for complicated sampling method. Statistically sound decision criterion can be derived for anomaly detection purpose from the perspective of the energy landscape of the data distribution. We investigate two decision criteria for performing anomaly detection: the energy score and the reconstruction error. Extensive empirical studies on benchmark tasks demonstrate that our proposed model consistently matches or outperforms all the competing methods.
Development of a Multiplex RNA Urine Test for the Detection and Stratification of Transitional Cell Carcinoma of the Bladder (2008)

Simple gene expression signatures can be used as urine markers for the accurate detection and characterization of bladder cancer.
Crystal structure of tetranectin, a trimeric plasminogen‐binding protein with an α‐helical coiled coil (1997)

Tetranectin is a plasminogen kringle 4-binding protein. The crystal structure has been determined at 2.8 A resolution using molecular replacement. Human tetranectin is a homotrimer forming a triple alpha-helical coiled coil. Each monomer consists of a carbohydrate recognition domain (CRD) connected to a long alpha-helix. Tetranectin has been classified in a distinct group of the C-type lectin superfamily but has structural similarity to the proteins in the group of collectins. Tetranectin has three intramolecular disulfide bridges. Two of these are conserved in the C-type lectin superfamily, whereas the third is present only in long-form CRDs. Tetranectin represents the first structure of a long-form CRD with intact calcium-binding sites. In tetranectin, the third disulfide bridge tethers the CRD to the long helix in the coiled coil. The trimerization of tetranectin as well as the fixation of the CRDs relative to the helices in the coiled coil indicate a demand for high specificity in the recognition and binding of ligands.
Monitoring melanoma recurrence with circulating tumor DNA: a proof of concept from three case studies (2019)

This study demonstrates promising results for the use of ctDNA as an informative monitoring tool for melanoma patients having undergone tumor resection of an early stage primary tumor. The clinical utility of ctDNA for monitoring disease recurrence warrants investigation in prospective studies as it may improve patient outcome.
Structure and function of microplasminogen: I. Methionine shuffling, chemical proteolysis, and proenzyme activation (1995)

We have cloned and expressed microplasminogen (mPlg), consisting of the N-terminal undecapeptide of human glu-Plg spliced to its proenzyme domain. This truncated (approximately 28 kDa) proenzyme retained the distinctive catalytic activities of the larger parent. Replacement of M residues followed by M shuffling permitted subsequent scission by site-directed chemical proteolysis (in CNBr/formic acid) without impairing any of the protein's characteristic properties. Activation of chymotrypsinogen-related zymogens occurs by limited proteolysis; the newly liberated, highly conserved N-terminus (VVGG) forms a salt bridge with an aspartyl residue immediately upstream of the active site serine. The role of both of these elements in mPlg activation was probed using protein engineering and site-directed proteolysis to alter the length and amino acid composition of the N-terminus, and to replace the aspartate. All modifications affected both Km and Kcat. The results identify some structural parameters of the N-terminus required for proenzyme activation.
A proximal conserved repeat in theXistgene is essential as a genomic element for X-inactivation in mouse (2008)

X-inactivation in female mammals is triggered by the association of non-coding Xist RNA in cis with the X chromosome. Although it has been suggested that the A-repeat located in the proximal part of the Xist RNA is required for chromosomal silencing in ES cells, its role in mouse has not yet been addressed. Here, we deleted the A-repeat in mouse and studied its effects on X-inactivation during embryogenesis. The deletion, when paternally transmitted, caused a failure of imprinted X-inactivation in the extraembryonic tissues, demonstrating the essential role of the A-repeat in X-inactivation in the mouse embryo. Unexpectedly, the failure of X-inactivation was caused by a lack of Xist RNA rather than by a defect in the silencing function of the mutated RNA, which we expected to be expressed from the mutated X. Interestingly, the normally silent paternal copy of Tsix, which is an antisense negative regulator of Xist, was ectopically activated in the preimplantation embryo. Furthermore, CpG sites in the promoter region of paternal Xist, which are essentially unmethylated in the extraembryonic tissues of the wild-type female embryo, acquire a significant level of methylation on the mutated paternal X. These findings demonstrate that the DNA sequence deleted on the mutated X, most probably the A-repeat, is essential as a genomic element for the appropriate transcriptional regulation of the Xist/Tsix loci and subsequent X-inactivation in the mouse embryo.
Differential Enhancement of Dengue Virus Immune Complex Infectivity Mediated by Signaling-Competent and Signaling-Incompetent Human FcγRIA (CD64) or FcγRIIA (CD32) (2006)

Fcgamma receptor (FcgammaR)-mediated entry of infectious dengue virus immune complexes into monocytes/macrophages is hypothesized to be a key event in the pathogenesis of complicated dengue fever. FcgammaRIA (CD64) and FcgammaRIIA (CD32), which predominate on the surface of such dengue virus-permissive cells, were compared for their influence on the infectivity of dengue 2 virus immune complexes formed with human dengue virus antibodies. A signaling immunoreceptor tyrosine-based activation motif (ITAM) incorporated into the accessory gamma-chain subunit that associates with FcgammaRIA and constitutively in FcgammaRIIA is required for phagocytosis mediated by these receptors. To determine whether FcgammaRIA and FcgammaRIIA activation functions are also required for internalization of infectious dengue virus immune complexes, we generated native and signaling-incompetent versions of each receptor by site-directed mutagenesis of ITAM tyrosine residues. Plasmids designed to express these receptors were transfected into COS-7 cells, and dengue virus replication was measured by plaque assay and flow cytometry. We found that both receptors mediated enhanced dengue virus immune complex infectivity but that FcgammaRIIA appeared to do so far more effectively. Abrogation of FcgammaRIA signaling competency, either by expression without gamma-chain or by coexpression with gamma-chain mutants, was associated with significant impairment of phagocytosis and of dengue virus immune complex infectivity. Abrogation of FcgammaRIIA signaling competency was also associated with equally impaired phagocytosis but had no discernible effect on dengue virus immune complex infectivity. These findings point to fundamental differences between FcgammaRIA and FcgammaRIIA with respect to their immune-enhancing capabilities and suggest that different mechanisms of dengue virus immune complex internalization may operate between these FcgammaRs.
WRFDA 2010 Status (2010)

WRFDA the Weather Research and Forecasting (WRF) Data Assimilation system is a component of the WRF modeling system developed at the National Center for Atmospheric Research. WRFDA is an advanced data assimilation system, contained with the WRF software that provides state-of-art 3D/4D variational (3D/4D-Var) and hybrid variational/ ensemble techniques (Barker et al. 2004; Huang et al. 2009a; Wang et al. 2008).