gebhart/patrepeval huggingface dataset:
Threonine dehydratases of <i>Corynebacterium glutamicum</i> with altered allosteric control: their generation and biochemical and structural analysis (1994)

Threonine dehydratase is the key enzyme in L-isoleucine synthesis, since it is allosterically feedback-inhibited by L-isoleucine. With the aim of obtaining regulatorily altered mutants of the threonine dehydratase of Corynebacterium glutamicum, amino acids were specifically exchanged and a new biological system of mutant selection was developed, based on the intoxication of Escherichia coli by ketobutyrate, which is the dehydratase reaction product. A collection of 19 mutant enzymes was generated and genetically and biochemically characterized comprising a whole range of regulatorily and catalytically altered enzymes. Of particular interest is the mutant Val-323-Ala, which is characterized by the fact that the L-isoleucine inhibition is entirely abolished so that the enzyme is always present in a relaxed, high-activity state. Correspondingly, the Hill coefficient is 1.4, in contrast to the value of 3.4 characteristic of the wild-type enzyme. Another peculiar mutant generated is the double mutant His-278-Arg-Leu-351-Ser. Here, again, L-isoleucine no longer inhibits catalytic activity, but the effector still promotes major structural changes of the protein, as ascertained from the L-isoleucine-dependent loss of pyridoxal-5'-phosphate from this mutant enzyme. Further enzymes obtained are reduced in L-isoleucine inhibition to a varying degree. Detailed studies on the structure of the enzyme revealed a partially very high similarity of the secondary structure to the mechanistically identical beta-subunit of the tryptophan synthase. This provides further indications concerning the localization of the regulatory and catalytic domain of the threonine dehydratase.
Selective recognition of fibroblast growth factor-2 by the long pentraxin PTX3 inhibits angiogenesis (2004)

The long pentraxin PTX3 is a soluble pattern recognition receptor produced by monocytes and endothelial cells that plays a nonredundant role in inflammation. Several pathologic conditions are characterized by local production of both PTX3 and the angiogenic fibroblast growth factor-2 (FGF2). Here, solid-phase binding assays demonstrated that PTX3 binds with high affinity to FGF2 but not to a panel of cytokines and growth factors, including FGF1, FGF4, and FGF8. Accordingly, PTX3 prevented (125)I-FGF2 binding to endothelial cell receptors, leading to specific inhibition of FGF2-induced proliferation. PTX3 hampered also the motogenic activity exerted by endogenous FGF2 on a wounded endothelial cell monolayer. Moreover, PTX3 cDNA transduction in FGF2-transformed endothelial cells inhibited their autocrine FGF2-dependent proliferation and morphogenesis in vitro and their capacity to generate vascular lesions when injected in nude mice. Finally, PTX3 suppressed neovascularization triggered by FGF2 in the chick embryo chorioallantoic membrane with no effect on physiologic angiogenesis. In contrast, the short pentraxin C-reactive protein was a poor FGF2 ligand/antagonist. These results establish the selective binding of a member of the pentraxin superfamily to a growth factor. PTX3/FGF2 interaction may modulate angiogenesis in various physiopathologic conditions driven by inflammation, innate immunity, and/or neoplastic transformation.
Engineering of the yeast antioxidant enzyme Mpr1 for enhanced activity and stability (2009)

The budding yeast Saccharomyces cerevisiae Sigma1278b has the MPR1 gene, which confers resistance to the proline analogue azetidine-2-carboxylate (AZC). This gene encodes an N-acetyltransferase Mpr1 that detoxifies AZC, and the homologous genes have been found in many yeasts. Recently, we found that Mpr1 protects yeast cells by reducing the intracellular reactive oxygen species (ROS) levels under oxidative stresses, such as heat-shock, freezing, or ethanol treatment. Unlike the known antioxidant enzymes, Mpr1 is thought to acetylate toxic metabolite(s) involved in ROS generation via oxidative events. To improve the enzymatic functions of Mpr1, we applied PCR random mutagenesis to MPR1. The mutagenized plasmid library was introduced into the S. cerevisiae S288C strain lacking MPR1, and we successfully isolated two Mpr1 variants with higher AZC resistance (K63R and F65L/L117V). Interestingly, overexpression of the K63R variant was found to increase cell viability or decrease intracellular ROS levels after exposure to H(2)O(2) or ethanol compared with the wild-type Mpr1. In vitro studies with the recombinant enzymes showed that the catalytic efficiency of the K63R variant for AZC and acetyl-CoA was higher than that of the wild-type Mpr1 and that the F65L mutation greatly enhanced the thermal stability. The mutational analysis and molecular modeling suggest that an alpha-helix containing Lys63 and Phe65 has important roles in the function of Mpr1. In addition, the wild-type and K63R variant Mpr1 reduced intracellular ROS levels under ethanol stress conditions on haploid sake yeast cells. These results suggest that engineering Mpr1 might be useful in breeding oxidative stress-tolerant yeast strains.
Efficient resonantly pumped 28-μm Er^3+:GSGG laser (1992)

Efficient cw operation of the Er(3+):GSGG (4)I(11/2)?(4)I(13/2) laser transition at 2.8 microm is demonstrated at room temperature. The (4)I(11/2) upper laser state is directly pumped at 0.97 microm. The slope efficiency for the 2.8-microm laser is 36%, indicating a greater than unity quantum efficiency. This excess efficiency results from the recycling of population through upconversion out of the lower laser state.
Clinical Predictors of Severe Complicated Clostridium Difficile Infection (2011)

Purpose:Clostridium Difficile infection (CDI) can be severe, and associated with complications and mortality. Treatment recommendations are stratified based on severity. However, there are no robust models to predict severe complicated CDI. The objective of this study was to create a clinically useful model to predict severe complicated CDI. Methods: The microbiology laboratory database and patient medical records were queried to identify cases of CDI from June 1, 2007 - May 31, 2010. Severe complicated CDI was defined as need for ICU admission or colectomy, or death within 30 days of CDI diagnosis. Variables including patient demographics, Charlson Co-morbidity index, temperature, peripheral leukocyte count, serum albumin, and change in serum creatinine were obtained. Univariate and multiple variable logistic regression models were used to assess the association of these variables with complications of CDI. Only patients who had data for each variable of interest were included in the multiple variable analyses. Results: The cohort included 1400 patients with CDI (50% female, median age at CDI diagnosis was 63.1 years [range 1.2-100.1]), and 357 (25.5%) were severe complicated CDI cases. The frequency of ICU admission, colectomy, and death within 30 days of diagnosis was 19.3%, 2.3%, and 7.3%, respectively. In univariate analysis, increasing age (OR 1.15, 95% CI 1.08-1.23, p<0.0001), increasing peripheral leukocyte count (OR 1.05, 95% CI 1.03-1.06, p<0.0001), change in serum creatinine >1.5 fold (OR 2.61, 95% CI 2.04-3.34, p<0.0001), serum albumin (OR 0.48, 95% CI 0.35-0.66, p<0.0001), temperature (OR 1.36, 95% CI 1.35-1.59, p=0.0002), and Charlson Co-morbidity index (OR 1.09, 95% CI 1.03-1.15, p=0.001) were associated with severe complicated CDI. Serum albumin and temperature were not included in the multiple variable model due to missing data. In the multiple variable model (adjusting for referral distance), increasing age (OR 1.1, 95% CI 1.03-1.18, p=0.0072), increasing peripheral leukocyte count (OR 1.04, 95% CI 1.03-1.05, p<0.0001) and change in serum creatinine greater than 1.5-fold (OR 2.3, 95% CI 1.75-2.98, p<0.0001) were independent predictors of severe complicated CDI, but Charlson Comorbidity index score was not. Conclusion: Older age, higher peripheral leukocyte count, and rising serum creatinine independently predicted severe complicated CDI. Temperature and low serum albumin were also associated with severe complicated CDI by univariate analysis. An appreciation of these variables could be pivotal in identifying patients at increased risk of CDI complications. It is conceivable that early aggressive monitoring and intervention in these patients could have beneficial effects.
Biological Nitrogen Removal System for Strong Contaminated Wastewater (2004)

We have newly developed a biological nitrogen removal system used the immobilized microorganism for strong contaminated wastewater such as the landfill permeate. It was discovered that a resistant bacteria for high concentration of ammonium ion, during the treatment of low ammonium wastewater. Applying this microorganism for the immobilization, we examine the growth condition and the efficiency of nitrogen reduction.
Mesoporous Yttria-Zirconia and Metal-Yttria-Zirconia Solid Solutions for Fuel Cells (2000)

A new class of binary mesoporous yttria–zirconia(YZ) and ternary mesoporous metal-YZ materials (M=electroactive Ni/Pt) is presented here (the Figure shows PtYZ) that displays the highest surface area of any known form of yttria-stabilized zirconia. These mesoporous materials form as solid solutions and retain their structural integrity to 800 °C, which bodes well for their possible utilization in fuel cells.
Linkage of Crohn’s disease-related serological phenotypes: <i>NFKB1</i> haplotypes are associated with anti-CBir1 and ASCA, and show reduced NF-κB activation (2008)

These results suggest that NFKB1 haplotypes induce dysregulation of innate immune responses by altering NF-kappaB expression. The results also show the use of EBV-transformed lymphoblastoid cell lines to conduct phenotypic studies of genetic variation.
Macro-to-Micro Interface for the Control of Cellular Organization (2013)

The spatial organization of cellular communities plays a fundamental role in determining intercellular communication and emergent behavior. However, few tools exist to modulate tissue organization at the scale of individual cells, particularly in the case of dynamic manipulation. Micromechanical reconfigurable culture achieves dynamic control of tissue organization by culturing adherent cells on microfabricated plates that can be shifted to reorganize the arrangement of the cells. While biological studies utilizing this approach have been previously reported, this paper focuses on the engineering of the device, including the mechanism for translating manual manipulation to precise microscale position control, fault-tolerant design for manufacture, and the synthetic-to-living interface.
Identification of a Gene Associated with Bt Resistance in <i>Heliothis virescens</i> (2001)

Transgenic crops producing insecticidal toxins from Bacillus thuringiensis (Bt) are widely used for pest control. Bt-resistant insect strains have been studied, but the molecular basis of resistance has remained elusive. Here, we show that disruption of a cadherin-superfamily gene by retrotransposon-mediated insertion was linked to high levels of resistance to the Bt toxin Cry1Ac in the cotton pest Heliothis virescens. Monitoring the early phases of Bt resistance evolution in the field has been viewed as crucial but extremely difficult, especially when resistance is recessive. Our findings enable efficient DNA-based screening for resistant heterozygotes by directly detecting the recessive allele.
Long-Term Treatment With Dipeptidyl Peptidase IV Inhibitor Improves Hepatic and Peripheral Insulin Sensitivity in the VDF Zucker Rat (2002)

Upon release into circulation, the potent insulin secretagogues glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are rapidly cleaved and inactivated by the enzyme dipeptidyl peptidase IV (DP IV). Long-term administration of specific DP IV inhibitors, so as to enhance circulating active GIP and GLP-1 levels, has been shown to improve glucose tolerance and beta-cell glucose responsiveness and to reduce hyperinsulinemia in the Vancouver diabetic fatty (VDF) rat model of type 2 diabetes. Using the VDF model, the current study was undertaken to examine the effects of long-term DP IV inhibitor treatment on insulin sensitivity. Euglycemic-hyperinsulinemic clamps were performed on two sets of conscious VDF rats treated with or without the DP IV inhibitor P32/98 (20 mg. kg(-1). day(-1) for 12 weeks). The protocol consisted of three sequential 90-min periods with insulin infusion rates of 0, 5, and 15 mU. kg(-1). min(-1) and included a constant infusion of [ (3)H]glucose for measure of hepatic and peripheral insulin sensitivity. Relative to untreated littermates, the treated animals showed a left shift in the sensitivity of hepatic glucose output to insulin (average reduction approximately 6 micro mol. kg(-1). min(-1)) and a marked gain in peripheral responsiveness to insulin, with glucose disposal rates increasing 105 and 216% in response to the two insulin steps (versus 2 and 46% in controls). These results provide the first demonstration of improved hepatic and peripheral insulin sensitivity after DP IV inhibitor therapy, and coupled with apparent improvements in beta-cell function, they offer strong support for the utility of these compounds in the treatment of diabetes.
Characterizing Human Pluripotent-Stem-Cell-Derived Vascular Cells for Tissue Engineering Applications (2014)

Tissue-engineered constructs are rendered useless without a functional vasculature owing to a lack of nutrients and oxygen. Cell-based approaches to reconstruct blood vessels can yield structures that mimic native vasculature and aid transplantation. Vascular derivatives of human induced pluripotent stem cells (hiPSCs) offer opportunities to generate patient-specific therapies and potentially provide unlimited amounts of vascular cells. To be used in engineered vascular constructs and confer therapeutic benefit, vascular derivatives must exhibit additional key properties, including extracellular matrix (ECM) production to confer structural integrity and growth factor production to facilitate integration. In this study, we examine the hypothesis that vascular cells derived from hiPSCs exhibit these critical properties to facilitate their use in engineered tissues. hiPSCs were codifferentiated toward early vascular cells (EVCs), a bicellular population of endothelial cells (ECs) and pericytes, under varying low-oxygen differentiation conditions; subsequently, ECs were isolated and passaged. We found that EVCs differentiated under low-oxygen conditions produced copious amounts of collagen IV and fibronectin as well as vascular endothelial growth factor and angiopoietin 2. EVCs differentiated under atmospheric conditions did not demonstrate such abundant ECM expression, but exhibited greater expression of angiopoietin 1. Isolated ECs could proliferate up to three passages while maintaining the EC marker vascular endothelial cadherin. Isolated ECs demonstrated an increased propensity to produce ECM compared with their EVC correlates and took on an arterial-like fate. These findings illustrate that hiPSC vascular derivates hold great potential for therapeutic use and should continue to be a preferred cell source for vascular construction.
Mimicking a New 2-Phenylethanol Production Pathway from <i>Proteus mirabilis</i> JN458 in <i>Escherichia coli</i> (2018)

Bacteria rarely produce natural 2-phenylethanol. We verified a new pathway from Proteus mirabilis JN458 to produce 2-phenylethanol using Escherichia coli to coexpress l-amino acid deaminase, α-keto acid decarboxylase, and alcohol dehydrogenase from P. mirabilis. Based on this pathway, a glucose dehydrogenase coenzyme regeneration system was constructed. The optimal conditions of biotransformation by the recombinant strain E-pAEAKaG were at 40 °C and pH 7.0. Finally, the recombinant strain E-pAEAKaG produced 3.21 ± 0.10 g/L 2-phenylethanol in M9 medium containing 10 g/L l-phenylalanine after a 16 h transformation. Furthermore, when the concentration of l-phenylalanine was 4 g/L (24 mM), the production of 2-phenylethanol reached 2.88 ± 0.18 g/L and displayed a higher conversion rate of 97.38 mol %.
Channel waveguides in electro-optic polymers using a photopolymer cladding technique (1991)

Reported here is a new fabrication technique for forming channel waveguides in organic electro-optic (EO) polymer materials. The process uses projection printing to directly expose inverted ridge channel patterns in a UV curing optical epoxy cladding layer. This technique is noncontact, requires no post processing, minimizes wall roughness, and can be used with any spin coatable EO polymer. Single-mode channel waveguides have been demonstrated and characterized as well as phase modulator devices.
3D Maskless Micropatterning for Regeneration of Highly Organized Tubular Tissues (2017)

Micropatterning is a widely used powerful tool to create highly ordered microstructures on material surfaces. However, due to technical limitations, the integration of micropatterned microstructures into bioinspired 3D scaffolds to successfully regenerate well-organized functional tissues is not achieved. In this work, a unique maskless micropatterning technology is reported to create 3D nanofibrous matrices with highly organized tubular architecture for tissue regeneration. This micropatterning method is a laser-guided, noncontact, high-precision, flexible computer programming of machining process that can create highly ordered tubules with the density ranged from 1000 to 60 000 mm<sup>-2</sup> and the size varied from 300 nm to 30 µm in the bioinspired 3D matrix. The tubular architecture presents pivotal biophysical cues to control dental pulp stem cell alignment, migration, polarization, and differentiation. More importantly, when using this 3D tubular hierarchical matrix as a scaffold, this study successfully regenerates functional tubular dentin that has the same well-organized microstructure as its natural counterpart. This 3D maskless micropattern approach represents a powerful avenue not only for the exploration of cell-material interactions in 3D, but also for the regeneration of functional tissues with well-organized microstructures.
Tissue Engineering: Biomedical Applications (1995)

This paper discusses a novel approach to tissue engineering involving seeding mammalian cells onto biodegradable polymer scaffolds, growing the cells on these scaffolds in vitro, and then implanting the cell-polymer constructs in vivo. Approaches for in vitro cultivation of cells are first discussed. The types of polymer scaffolds that are utilized and the kinds of bioreactor conditions for growing cells are then delineated. The application of this approach in vitro and in vivo for producing cartilage, tendon, liver, urothelial tissue, intestine, and bone are then examined.
Targeting the Platelet Integrin GPIIb/IIIa (2010)

The platelet integrin GPIIb/IIIa plays an essential role in thrombus formation through interactions with adhesive ligands and has emerged as a primary target for the development of anti-thrombotic agents. Receptor activation is under strict control, with activators, inhibitors, and signalling mechanisms controlling its conformation. Structural biology research has produced high-resolution images defining the ligand binding site at the atomic level. Successful blockade of this ligand binding has validated GPIIb/IIIa as a therapeutic target in cardiovascular medicine. GPIIb/IIIa inhibitors were the first rationally designed anti-platelet agents and have been used effectively in a wide variety of clinical scenarios including unstable angina, myocardial infarction, and high risk percutaneous coronary interventions with and without intracoronary stenting. Three inhibitors (abciximab, eptifibatide, and tirofiban) are currently licensed for human use. Surprisingly, oral GPIIb/IIIa antagonists have not been successful and there is an unmet need for effective anti-GPIIb/IIIa drugs that cause less bleeding problems and that can be orally applied. Here we review our current knowledge about GPIIb/IIIa structure, signalling pathways and receptor function, the benefits and limitations of current GPIIb/IIIa blockers and we take a look forward how the lessons learned from the mixture of success and failure of GPIIb/IIIa blocker development can be transformed in new and better GPIIb/IIIa blockers.
Investigation of Photon-Generated Leakage Current for High-Performance Active Matrix Micro-LED Displays (2016)

In this paper, we investigated leakage current generated by light emission of micro-light emitting diode (LED) pixels in active matrix (AM) micro-LED displays. Customdesigned structures of metal cover with different coverage lengths were designed and fabricated to completely eliminate the photongenerated leakage current, thus enhancing the performance of AM driving circuits. Working principle of two transistors and one capacitor AM pixel and requirement of its driving transistors were also systematically discussed for liquid crystal displays, organic LED displays, and LED microdisplays. Transistors with the optimized metal-cover design have an ON/OFF-current ratio of 108, which is two orders of magnitude higher than those without metal cover. This concept was successfully implemented in a high-resolution and fine-pitch AM micro-LED display with a resolution of 400 × 240 and a pixel pitch of 30 μm. Vivid images and movies were presented to show the great potential for wearable applications.
Three and four product surface-wave acousto-optic time integrating correlators (1985)

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Maximum likelihood detection for coded combinerless LINC-OFDM systems (2016)

Owning to the high peak-to-average power ratio problem, the power efficiency of orthogonal-frequency-division-multiplexing (OFDM) systems is usually low. It deteriorates in millimeter wave systems in which the design of an efficient linear power amplifier is much more challenging. The linear-amplification-with-nonlinear-component (LINC) technique can serve as a remedy, decomposing the input signal into two constant-envelop component signals followed by high-efficient nonlinear amplifiers. However, the power combiner, a key component used to combine the amplified signals, is difficult to implement. Combinerless LINC systems employ two transmit antennas such that two component signals can be naturally combined at the receiver. Unfortunately, the performance of combinerless LINC-OFDM systems is seriously degraded if difference, even small, exists between the two channels. The maximum likelihood (ML) receiver can effectively solve the problem; however, its computational complexity is prohibitedly high. We propose a coded combinerless LINC-OFDM system, including a convolutional encoder and a list Viterbi algorithm (LVA) decoder, to solve the problem. The LVA can provide a small number of candidates for the ML detector, dramatically reducing the required computational complexity. We also utilize an enhanced zero-forcing equalizer such that the soft-demapping operation can be effectively conducted. Finally, we propose a simple iterative interference cancellation scheme to further enhance the performance. Simulations show that the proposed combinerless LINC-OFDM system can outperform the conventional OFDM while the consumed power is much lower.