gebhart/patrepeval huggingface dataset:
Structural basis for cytosolic double-stranded RNA surveillance by human oligoadenylate synthetase 1 (2013)

The human sensor of double-stranded RNA (dsRNA) oligoadenylate synthetase 1 (hOAS1) polymerizes ATP into 2',5'-linked iso-RNA (2-5A) involved in innate immunity, cell cycle, and differentiation. We report the crystal structure of hOAS1 in complex with dsRNA and 2'-deoxy ATP at 2.7 Å resolution, which reveals the mechanism of cytoplasmic dsRNA recognition and activation of oligoadenylate synthetases. Human OAS1 recognizes dsRNA using a previously uncharacterized protein/RNA interface that forms via a conformational change induced by binding of dsRNA. The protein/RNA interface involves two minor grooves and has no sequence-specific contacts, with the exception of a single hydrogen bond between the -NH(2) group of nucleobase G17 and the carbonyl oxygen of serine 56. Using a biochemical readout, we show that hOAS1 undergoes more than 20,000-fold activation upon dsRNA binding and that canonical or GU-wobble substitutions produce dsRNA mutants that retain either full or partial activity, in agreement with the crystal structure. Ultimately, the binding of dsRNA promotes an elaborate conformational rearrangement in the N-terminal lobe of hOAS1, which brings residues D75, D77, and D148 into proximity and creates coordination geometry for binding of two catalytic Mg(2+) ions and ATP. The assembly of this critical active-site structure provides the gate that couples binding of dsRNA to the production and downstream functions of 2-5A.
Annular arrayed-waveguide fiber for autofocusing Airy-like beams (2016)

We propose and theoretically demonstrate a novel optical fiber with an annular arrayed-waveguide to implement Airy phase and amplitude modulation, and generate an abruptly autofocusing circular Airy beam. The properties of wave propagation in Airy fiber and free space are studied by using the coupled-mode theory and angular spectrum method. The calculated results show that the output beam from such a fiber has a circular Airy-like pattern and can autofocus with the intensity maxima following a parabolic trajectory. We also show that the position of the focus point of the output beam from the Airy fiber can be easily controlled by changing input wavelength.
Enhancement of Metastatic Potential of Murine and Human Melanoma Cells by Laminin Receptor Peptide G: Attachment of Cancer Cells to Subendothelial Matrix as a Pathway for Hematogenous Metastasis (1993)

Our findings suggest that direct adhesion of tumor cells to the subendothelial matrix is a main pathway for hematogenous metastases and that tumor cell-matrix interaction may be more relevant than tumor cell-endothelial cell attachment in this process.
Evaluation of Castor Oil Samples for Potential Toxin Contamination (2016)

Abstract Castor oil and its derivatives are widely used as a chemical feedstock for production of lubricants and greases, engineering plastics, plasticizers and surfactants. It also has wide application in consumer goods such as lipstick, deodorants and medicinal uses. Due to concerns about the possible presence of the ricin toxin in the oil, we have tested a collection of castor oils processed using different approaches, including cold‐pressed, US Pharmaceutical (USP) grade, and neutralized oils. Water soluble proteins were extracted from oil samples into phosphate‐buffered saline containing 0.05 % bovine serum albumin (PBSB) and analyzed for potential ricin contamination by ELISA. Our results indicate that only the cold‐pressed castor oil contained measurable levels of the toxin, estimated to be 35 ± 13 μg/l. A normal oral dose of castor oil for laxative use is 14 ml, so even cold‐pressed castor oil would be well below the toxic level of 1–5 μg/kg body weight. However, the presence of the toxin indicates that other soluble proteins, including allergens, may be present in cold‐pressed castor oil.
The Genes degQ , pps , and lpa-8 ( sfp ) Are Responsible for Conversion of Bacillus subtilis 168 to Plipastatin Production (1999)

Bacillus subtilis YB8 produces the lipopeptide antibiotic plipastatin. B. subtilis MI113, which is a derivative of strain 168, was converted into a new plipastatin producer, strain 406, by competence transformation with the chromosomal DNA of YB8. Transposon mini-Tn10 insertional mutagenesis was applied to strain 406, which revealed that lpa-8 (sfp) (encoding 4'-phosphopantetheinyl transferase) and the pps operon (located between 167 and 171 degrees ) are essential for plipastatin production. The pps operon was previously suggested to encode putative peptide synthetases (A. Tognoni, E. Franchi, C. Magistrelli, E. Colombo, P. Cosmina, and G. Grandi, Microbiology 141:645-648, 1995) and was thought to be the fengycin operon (V. Tosato, A. M. Albertini, M. Zotti, S. Sonda, and C. V. Bruschi, Microbiology 143:3443-3450, 1997). We claim that the pps operon is the pli operon, encoding plipastatin synthetase. By using a new high-performance liquid chromatography system, we revealed that strain 168 expressing only lpa-8 can also produce plipastatin, although the yield is very low. However, the introduction of the pleiotropic regulator degQ of strain YB8 into strain 168 expressing lpa-8 resulted in a 10-fold increase in the production of plipastatin.
Heparan/Chondroitin Sulfate Biosynthesis (2000)

Human beta1,3-glucuronyltransferase I (GlcAT-I) is a central enzyme in the initial steps of proteoglycan synthesis. GlcAT-I transfers a glucuronic acid moiety from the uridine diphosphate-glucuronic acid (UDP-GlcUA) to the common linkage region trisaccharide Gal beta 1-3Gal beta 1-4Xyl covalently bound to a Ser residue at the glycosaminylglycan attachment site of proteoglycans. We have now determined the crystal structure of GlcAT-1 at 2.3 A in the presence of the donor substrate product UDP, the catalytic Mn(2+) ion, and the acceptor substrate analog Gal beta 1-3Gal beta 1-4Xyl. The enzyme is a alpha/beta protein with two subdomains that constitute the donor and acceptor substrate binding site. The active site residues lie in a cleft extending across both subdomains in which the trisaccharide molecule is oriented perpendicular to the UDP. Residues Glu(227), Asp(252), and Glu(281) dictate the binding orientation of the terminal Gal-2 moiety. Residue Glu(281) is in position to function as a catalytic base by deprotonating the incoming 3-hydroxyl group of the acceptor. The conserved DXD motif (Asp(194), Asp(195), Asp(196)) has direct interaction with the ribose of the UDP molecule as well as with the Mn(2+) ion. The key residues involved in substrate binding and catalysis are conserved in the glucuronyltransferase family as well as other glycosyltransferases.
The Role of the Acidity of N-Heteroaryl Sulfonamides as Inhibitors of Bcl-2 Family Protein–Protein Interactions (2013)

Overexpression of the antiapoptotic members of the Bcl-2 family of proteins is commonly associated with cancer cell survival and resistance to chemotherapeutics. Here, we describe the structure-based optimization of a series of N-heteroaryl sulfonamides that demonstrate potent mechanism-based cell death. The role of the acidic nature of the sulfonamide moiety as it relates to potency, solubility, and clearance is examined. This has led to the discovery of novel heterocyclic replacements for the acylsulfonamide core of ABT-737 and ABT-263.
The effect of orientation on the visual resolution of gratings (1966)

1. Visual resolving power is known to be poorer for objects oriented obliquely as compared with horizontal and vertical orientations. Experiments were designed to evaluate the optical and neurophysiological factors involved.2. Gratings with a sinusoidal light distribution were generated on the face of an oscilloscope. Spatial frequency and contrast could be varied while keeping the mean luminance of the grating constant.3. Using a homatropinized eye with an artificial pupil and carefully corrected refraction, high resolution in the vertical and horizontal meridians as compared with the oblique meridians was found for gratings ranging in spatial frequency from 1 to 35 c/deg.4. It is concluded from the similar behaviour of low and high frequency gratings that neither focus errors nor optical aniseikonia can account for these findings.5. Additional proof that optical factors cannot significantly account for these preferred directions of resolution was obtained by forming interference fringes directly on the retina using a neon-helium laser as a coherent light source.6. Similar orientational changes in resolution were found by by-passing the dioptrics with interference fringes. It is concluded that the effect is due to some orientational inequality in the visual nervous system.
Selection for Early Flowering in Corn: 10 Late Synthetics (1985)

The purpose of this study was to determine if selection for earliness and better stalk quality in late synthetics would be effective. Ten corn ( Zea mays L.) synthetics adapted to southern Iowa and northern Missouri were grown at high plant density in southern Minnesota near Mankato. The earliest 5% to flower were selected for 11 generations and selection for better stalk quality was also enforced, during the last six cycles. The original populations and the 11 selected cycles were then compared in performance trials at moderate plant density over 3 years. Selection effect per cycle for 11 cyclea averaged: l I Celsius heat units (about 1 day) less to pollen shed; 1.4 points less grain moisture; 23 mm less plant height; 0.3 days less silk delay; 167 kg ha ∕1 (5%) more yle|d; and 0.5% more broken stalks. Comparing cycles 0 to 5 (selection for early flowering only) with cycles 6 to 11 (selection for early flowering plus better stalk quality) showed that effective selection for earlier flowering and associated less grain moisture continued in cycles 6 to 11, but at a decreased rate. Gain from selectsion against silk delay was reduced in cycles 6 to 11 because near‐optimum performance had been attained. Selection for better stalk quality was effective in cycles 6 to 11, and the number of broken stalks at harvest was stabilized. We recommend selection for early flowering with or without stalk quality selection to make. late, exotic materials earlier, thereby enhancing their potential contribution of useful genetic diversity to the U.S. Corn Bellt.
Integration of a Spectral Domain Optical Coherence Tomography System into a Surgical Microscope for Intraoperative Imaging (2011)

High-quality retinal imaging is feasible with an MMOCT system. Intraoperative imaging with model eyes provides high-resolution depth information including visualization of the instrument and intraoperative tissue manipulation. This study demonstrates a key component of an interactive platform that could provide enhanced information for the vitreoretinal surgeon.
Correction of Enzymatic and Lysosomal Storage Defects in Fabry Mice by Adenovirus-Mediated Gene Transfer (1999)

Fabry disease is a recessive, X-linked disorder caused by a deficiency of the lysosomal hydrolase alpha-galactosidase A. Deficiency of this enzyme results in progressive deposition of the glycosphingolipid globotriaosylceramide (GL-3) in the vascular lysosomes, with resultant distension of the organelle. The demonstration of a secretory pathway for lysosomal enzymes and their subsequent recapture by distant cells through the mannose 6-phosphate receptor pathway has provided a rationale for somatic gene therapy of lysosomal storage disorders. Toward this end, recombinant adenoviral vectors encoding human alpha-galactosidase A (Ad2/CEHalpha-Gal, Ad2/CMVHIalpha-Gal) were constructed and injected intravenously into Fabry knockout mice. Administration of Ad2/CEHalpha-Gal to the Fabry mice resulted in an elevation of alpha-galactosidase A activity in all tissues, including the liver, lung, kidney, heart, spleen, and muscle, to levels above those observed in normal animals. However, enzymatic expression declined rapidly such that by 12 weeks, only 10% of the activity observed on day 3 remained. Alpha-galactosidase A detected in the plasma of injected animals was in a form that was internalized by Fabry fibroblasts grown in culture. Such internalization occurred via the mannose 6-phosphate receptors. Importantly, concomitant with the increase in enzyme activity was a significant reduction in GL-3 content in all tissues to near normal levels for up to 6 months posttreatment. However, as expression of alpha-galactosidase A declined, low levels of GL-3 reaccumulated in some of the tissues at 6 months. For protracted treatment, we showed that readministration of recombinant adenovirus vectors could be facilitated by transient immunosuppression using a monoclonal antibody against CD40 ligand (MR1). Together, these data demonstrate that the defects in alpha-galactosidase A activity and lysosomal storage of GL-3 in Fabry mice can be corrected by adenovirus-mediated gene transfer. This suggests that gene replacement therapy represents a viable approach for the treatment of Fabry disease and potentially other lysosomal storage disorders.
Development of Chemical Oxygen Demand On-Line Monitoring System Based on a Photoelectrochemical Degradation Principle (2006)

A simple, rapid, and sensitive on-line chemical oxygen demand (COD) determination method has been proposed and experimentally validated. The method is based on a photoelectrochemical oxidative degradation principle and operates under a continuous flow mode. The method employs a specially designed thin-layer photoelectrochemical cell that incorporates a highly effective nanoparticulate TiO2 photoanode. This approach overcomes many problems associated with the conventional COD determination techniques such as long analysis time, consumption of expensive and toxic reagents, production of secondary toxic waste, and poor reproducibility. The effect of important experimental parameters on the analytical signal generation was systematically investigated, and the optimum conditions were obtained. The method was successfully applied to determine the COD of real samples from various industrial wastewaters. The COD value of real samples determined by this method agreed well with the standard dichromate method. The assay time of 1-5 min/sample can be readily achieved. A practical detection limit of 1 mg L(-1) COD with a linear range of 1-100 mg L(-1) was achieved under the optimum conditions.
Improving duplicate elimination in storage systems (2006)

Minimizing the amount of data that must be stored and managed is a key goal for any storage architecture that purports to be scalable. One way to achieve this goal is to avoid maintaining duplicate copies of the same data. Eliminating redundant data at the source by not writing data which has already been stored not only reduces storage overheads, but can also improve bandwidth utilization. For these reasons, in the face of today's exponentially growing data volumes, redundant data elimination techniques have assumed critical significance in the design of modern storage systems.Intelligent object partitioning techniques identify data that is new when objects are updated, and transfer only these chunks to a storage server. In this article, we propose a new object partitioning technique, called fingerdiff , that improves upon existing schemes in several important respects. Most notably, fingerdiff dynamically chooses a partitioning strategy for a data object based on its similarities with previously stored objects in order to improve storage and bandwidth utilization. We present a detailed evaluation of fingerdiff , and other existing object partitioning schemes, using a set of real-world workloads. We show that for these workloads, the duplicate elimination strategies employed by fingerdiff improve storage utilization on average by 25%, and bandwidth utilization on average by 40% over comparable techniques.
The Bradyrhizobium japonicum rpoH1 gene encoding a sigma 32-like protein is part of a unique heat shock gene cluster together with groESL1 and three small heat shock genes (1996)

The heat shock response of Bradyrhizobium japonicum is controlled by a complex network involving two known regulatory systems. While some heat shock genes are controlled by a highly conserved inverted-repeat structure (CIRCE), others depend on a sigma 32-type heat shock sigma factor. Using Western blot (immunoblot) analysis, we confirmed the presence of a sigma 32-like protein in B. japonicum and defined its induction pattern after heat shock. A B. japonicum rpoH-like gene (rpoH1) was cloned by complementation of an Escherichia coli strain lacking sigma 32. A knockout mutation in rpoH1 did not abolish sigma 32 production in B. japonicum, and the rpoH1 mutant showed the wild-type growth phenotype, suggesting the presence of multiple rpoH homologs in this bacterium. Further characterization of the rpoH1 gene region revealed that the rpoH1 gene is located in a heat shock gene cluster together with the previously characterized groESL1 operon and three genes encoding small heat shock proteins in the following arrangement: groES1, groEL1, hspA, rpoH1, hspB, and hspC. Three heat-inducible promoters are responsible for transcription of the six genes as three bicistronic operons. A sigma 32-dependent promoter has previously been described upstream of the groESL1 operon. Although the hspA-rpoH1 and hspBC operons were clearly heat inducible, they were preceded by sigma 70-like promoters. Interestingly, a stretch of about 100 bp between the transcription start site and the start codon of the first gene in each of these two operons was nearly identical, making it a candidate for a regulatory element potentially allowing heat shock induction of sigma 70-dependent promoters.
The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP (2008)

Lung cancers caused by activating mutations in the epidermal growth factor receptor (EGFR) are initially responsive to small molecule tyrosine kinase inhibitors (TKIs), but the efficacy of these agents is often limited because of the emergence of drug resistance conferred by a second mutation, T790M. Threonine 790 is the "gatekeeper" residue, an important determinant of inhibitor specificity in the ATP binding pocket. The T790M mutation has been thought to cause resistance by sterically blocking binding of TKIs such as gefitinib and erlotinib, but this explanation is difficult to reconcile with the fact that it remains sensitive to structurally similar irreversible inhibitors. Here, we show by using a direct binding assay that T790M mutants retain low-nanomolar affinity for gefitinib. Furthermore, we show that the T790M mutation activates WT EGFR and that introduction of the T790M mutation increases the ATP affinity of the oncogenic L858R mutant by more than an order of magnitude. The increased ATP affinity is the primary mechanism by which the T790M mutation confers drug resistance. Crystallographic analysis of the T790M mutant shows how it can adapt to accommodate tight binding of diverse inhibitors, including the irreversible inhibitor HKI-272, and also suggests a structural mechanism for catalytic activation. We conclude that the T790M mutation is a "generic" resistance mutation that will reduce the potency of any ATP-competitive kinase inhibitor and that irreversible inhibitors overcome this resistance simply through covalent binding, not as a result of an alternative binding mode.
Growth of Uniformly Oriented Silica MFI and BEA Zeolite Films on Substrates (2011)

Applications of zeolite films benefit from alignment of the integrated channels, but methods for film growth have nearly always introduced orientational randomization in the direction normal to the substrate. We now report facile methods to grow silicalite-1 films and pure silica beta zeolite films on substrates with straight or sinusoidal channels positioned uniformly upright at a thickness of up to 8 micrometers. Precise gel compositions and processing temperatures are critical to promote secondary growth on pre-formed oriented crystal monolayers while suppressing self-crystallization in the bulk medium. Preliminary results highlight the potential of these uniformly oriented films in the nonlinear optical response and separation of xylene isomers.
Food Security: The Challenge of Feeding 9 Billion People (2010)

Continuing population and consumption growth will mean that the global demand for food will increase for at least another 40 years. Growing competition for land, water, and energy, in addition to the overexploitation of fisheries, will affect our ability to produce food, as will the urgent requirement to reduce the impact of the food system on the environment. The effects of climate change are a further threat. But the world can produce more food and can ensure that it is used more efficiently and equitably. A multifaceted and linked global strategy is needed to ensure sustainable and equitable food security, different components of which are explored here.
Porcine Carbonyl Reductase (2001)

Porcine testicular carbonyl reductase (PTCR) belongs to the short chain dehydrogenases/reductases (SDR) superfamily and catalyzes the NADPH-dependent reduction of ketones on steroids and prostaglandins. The enzyme shares nearly 85% sequence identity with the NADPH-dependent human 15-hydroxyprostaglandin dehydrogenase/carbonyl reductase. The tertiary structure of the enzyme at 2.3 A reveals a fold characteristic of the SDR superfamily that uses a Tyr-Lys-Ser triad as catalytic residues, but exhibits neither the functional homotetramer nor the homodimer that distinguish all SDRs. It is the first known monomeric structure in the SDR superfamily. In PTCR, which is also active as a monomer, a 41-residue insertion immediately before the catalytic Tyr describes an all-helix subdomain that packs against interfacial helices, eliminating the four-helix bundle interface conserved in the superfamily. An additional anti-parallel strand in the PTCR structure also blocks the other strand-mediated interface. These novel structural features provide the basis for the scaffolding of one catalytic site within a single molecule of the enzyme.
ABC transporter inhibitors that are substrates enhance lentiviral vector transduction into primitive hematopoietic progenitor cells (2004)

High gene transfer efficiencies have been difficult to achieve in hematopoietic progenitor cells (HPCs) but are important to therapeutic success of HPC gene therapy. Efficient gene transfer is especially challenging with use of column-purified vector for clinical application, as opposed to centrifuged vector commonly used for research. We investigated novel approaches to increase transduction by using a clinically applicable protocol and quantities of column-purified lentiviral vector. Recognizing the association of adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporters with HPC biology, we investigated the effect of transporter inhibitors on transduction. We found the ABC transporter inhibitor verapamil improved transduction efficiency 2- to 6-fold into CD34(+) cells isolated from mobilized peripheral blood, bone marrow, and cord blood. Verapamil also improved transduction in human SCID (severe combined immunodeficient) repopulating cell (SRC) transduction 3- to 4-fold, resulting in 80% to 90% transduction levels in mice receiving primary and secondary transplants without alterations in multilineage reconstitution. Additional ABC transporter substrate inhibitors like quinidine, diltiazem, and ritonavir also enhanced transduction 2- to 3-fold, although ABC transporter inhibitors that are not substrates did not. Enhanced transduction was not observed in mature hematopoietic cells, neurospheres, mesenchymal stem cells, or hepatocytes. Enhancement of transduction in HPCs was observed with vesicular stomatitis virus-G (VSV-G)-pseudotyped lentiviral vector but not with vector pseudotyped with RD114. Thus, we present a new approach for efficient delivery to primitive HPCs by VSV-G-pseudotyped lentiviral vectors.