gebhart/patrepeval huggingface dataset:
The chitinase 3-like protein human cartilage glycoprotein 39 inhibits cellular responses to the inflammatory cytokines interleukin-1 and tumour necrosis factor-alpha (2004)

Expression of the chitinase 3-like protein HC-gp39 (human cartilage glycoprotein 39) is associated with conditions of increased matrix turnover and tissue remodelling. High levels of this protein have been found in sera and synovial fluids of patients with inflammatory and degenerative arthritis. In order to assess the role of HC-gp39 in matrix degradation induced by inflammatory cytokines, we have examined its effect on the responses of connective tissue cells to TNF-alpha (tumour necrosis factor-alpha) and IL-1 (interleukin-1) with respect to activation of signalling pathways and production of MMPs (matrix metalloproteases) and chemokines. Stimulation of human skin fibroblasts or articular chondrocytes with IL-1 or TNF-alpha in the presence of HC-gp39 resulted in a marked reduction of both p38 mitogen-activated protein kinase and stress-activated protein kinase/Jun N-terminal kinase phosphorylation, whereas nuclear translocation of nuclear factor kappaB proceeded unimpeded. HC-gp39 suppressed the cytokine-induced secretion of MMP1, MMP3 and MMP13, as well as secretion of the chemokine IL-8. The suppressive effects of HC-gp39 were dependent on phosphoinositide 3-kinase activity, and treatment of cells with HC-gp39 resulted in AKT-mediated serine/threonine phosphorylation of apoptosis signal-regulating kinase 1. This process could therefore be responsible for the down-regulation of cytokine signalling by HC-gp39. These results suggest a physiological role for HC-gp39 in limiting the catabolic effects of inflammatory cytokines.
Synthesis and preliminary biological studies of hemifluorinated bifunctional bolaamphiphiles designed for gene delivery (2006)

The multistep synthesis of a new series of dissymmetric hemifluorocarbon bolaamphiphiles designed for gene transport is described. The dissymmetric functionalization of diiodoperfluoroctane leads to bolaamphiphile molecules composed of a partially fluorocarbon core end-capped with a glycoside and an ammonium salt derived from histidine or lysine. Initial biological results indicate that one of the bolaamphiphile—end-capped with a lysine and a lactobionamide residue—induces a remarkably low cytotoxicity on COS-7 cells and, when self-assembled with DNA plasmid, generates a significant in vitro transfection efficiency without the addition of any fusogenic lipid.
Polyalanine-Based Peptides as Models for Self-Associated β-Pleated-Sheet Complexes (1997)

The occurrence of beta-sheet motifs in a number of neurodegenerative disorders has brought about the need for the de novo design of soluble model beta-sheet complexes. Such model complexes are expected to further the understanding of the interconversion processes that occur from cellular allowed random coil or alpha-helical conformation into insoluble cell-deleterious beta-pleated-sheet motifs. In the present study, polyalanine-based peptides (i.e., derived from Ac-KA14K-NH2) were designed that underwent conformational changes from monomeric random coil conformations into soluble, macromolecular beta-pleated-sheet complexes without any covalent modification. The interconversion was found to be length-, environment-, and concentration-dependent and to be driven by hydrophobic interactions between the methyl groups of the alanine side chains. A series of substitution analogs of Ac-KA14K-NH2 was used to study the amino acid acceptability within the hydrophobic core of the complex, as well as at both termini. The formation of amyloid plaques in a number of amyloidogenic peptides could be related to the presence of amino acids within their sequences that were found to have a high propensity to occur in these model beta-sheet complexes.
Tracking and Quantitation of Retroviral-Mediated Transfer Using a Completely Humanized, Red-Shifted Green Fluorescent Protein Gene (1997)

We have developed murine retroviral vectors (RVs) containing an optimized green fluorescent protein (GFP) gene to study retroviral gene transfer and expression in living cells. We used the codon "humanized", "red-shifted" GFP gene, hGFP-S65T, a gain of function variant of the wild-type GFP from the jellyfish Aequorea victoria. We cloned the hGFP-S65T gene into the RV plasmid pLNCX (pLNChG65T). A stable amphotropic RV-producer cell line (VPC), designated LNChG65T VPC, was generated that exhibited bright fluorescence in greater than 95% of the cells. Human A375 melanoma cells and IGROV ovarian carcinoma cells transduced from LNCh-G65T VPC demonstrated high levels of fluorescence. The expression of a single integrated hGFP-S65T gene in eukaryotic cells provides a powerful tool to study gene transfer, expression and functional studies in vitro and in vivo.
Satisfiability-based layout revisited (1999)

lier BDD-based methods. Boolean-based routing transforms the geometric FPGA routing task into a single, large Boolean equation with the property that any assignment of input variables that "satisfies" the equation (that renders equation identically "1") specifies a valid routing. The formulation has the virtue that it considers all nets simultaneously, and the absence of a satisfying assignment implies that the layout is unroutable. Initial Boolean-based approaches to routing used Binary Decision Diagrams (BDDs) to represent and solve the layout problem. BDDs, however, limit the size and complexity of the FPGAs that can be routed, leading these approaches to concentrate only on individual FPGA channels. In this paper, we present a new search-based Satisfiability (SAT) formulation that can handle entire FPGAs, routing all nets concurrently. The approach relies on a recently developed SAT engine (GRASP) that uses systematic search with conflict-directed non-chronological backtracking, capable of handling very large SAT instances. We present the first comparisons of search-based SAT routing results to other routers, and offer the first evidence that SAT methods can actually demonstrate the unroutability of a layout. Preliminary experimental results suggest that this approach to FPGA routing is more viable than ear-1.1
An automated algorithm for analysis of 2-D echocardiographic short-axis images: a brief overview (1996)

The purpose of this report is to present a brief overview of a computer-based method designed to automatically approximate the epicardial and endocardial borders of the heart for echocardiographic images acquired from the parasternal transthoracic short-axis view. The only user input required is the end diastolic (ED) and end systolic (ES) frame numbers. The method was tested off-line on a developmental database acquired retrospectively from 55 patient studies (2 cycles/patient). The measurements provided by the computer-based method were comparable to those made by 3 expert observers.
Carbon Nanotube Delivery of the GFP Gene into Mammalian Cells (2005)

Special delivery. Amino-functionalized multiwalled carbon nanotubes (NH2-MWCNTs) were found to interact with negatively charged DNA and the cell membrane (see figure). Through this interaction, NH2-MWCNTs successfully delivered the GFP (green fluorescent protein) gene into mammalian cells without any cytotoxicity. The results show that NH2-MWCNT is a novel gene carrier and has potential application in gene delivery.
Recent progress in genome engineering techniques in the silkworm, Bombyx mori (2013)

Rapid advances in genome engineering tools, such as zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and the clustered regularly interspaced palindromic repeats/CRISPR-associated (CRISPR/Cas) system, have enabled efficient gene knockout experiments in a wide variety of organisms. Here, we review the recent progress in targeted gene disruption techniques in the silkworm, Bombyx mori. Although efficiency of targeted mutagenesis was very low in an early experiment using ZFNs, recent studies have shown that TALENs can induce highly efficient mutagenesis of desired target genes in Bombyx. Notably, mutation frequencies induced by TALENs can reach more than 50% of G0 gametes. Thus, TALENs can now be used as a standard tool for gene targeting studies, even when mutant phenotypes are unknown. We also propose guidelines for experimental design and strategy for knockout experiments in Bombyx. Genome editing technologies will greatly increase the usefulness of Bombyx as a model for lepidopteran insects, the major agricultural pests, and lead to sophisticated breeding of Bombyx for use in sericulture and biotechnology.
Expression, Crystallization, and Three-dimensional Structure of the Catalytic Domain of Human Plasma Kallikrein (2005)

Plasma kallikrein is a serine protease that has many important functions, including modulation of blood pressure, complement activation, and mediation and maintenance of inflammatory responses. Although plasma kallikrein has been purified for 40 years, its structure has not been elucidated. In this report, we described two systems (Pichia pastoris and baculovirus/Sf9 cells) for expression of the protease domain of plasma kallikrein, along with the purification and high resolution crystal structures of the two recombinant forms. In the Pichia pastoris system, the protease domain was expressed as a heterogeneously glycosylated zymogen that was activated by limited trypsin digestion and treated with endoglycosidase H deglycosidase to reduce heterogeneity from the glycosylation. The resulting protein was chromatographically resolved into four components, one of which was crystallized. In the baculovirus/Sf9 system, homogeneous, crystallizable, and nonglycosylated protein was expressed after mutagenizing three asparagines (the glycosylation sites) to glutamates. When assayed against the peptide substrates, pefachrome-PK and oxidized insulin B chain, both forms of the protease domain were found to have catalytic activity similar to that of the full-length protein. Crystallization and x-ray crystal structure determination of both forms have yielded the first three-dimensional views of the catalytic domain of plasma kallikrein. The structures, determined at 1.85 A for the endoglycosidase H-deglycosylated protease domain produced from P. pastoris and at 1.40 A for the mutagenically deglycosylated form produced from Sf9 cells, show that the protease domain adopts a typical chymotrypsin-like serine protease conformation. The structural information provides insights into the biochemical and enzymatic properties of plasma kallikrein and paves the way for structure-based design of protease inhibitors that are selective either for or against plasma kallikrein.
Practical study on wireless transmission of power and information for autonomous decentralized manufacturing system (1999)

In previous papers, the authors have already introduced the idea of an autonomous decentralized manufacturing system (ADMS), in which machines receive electrical energy through wireless power transmission and also are decentrally controlled through wireless transmission of the control and feedback data. With this idea, the degree of freedom in motion control is enlarged, and the system has the capability of adaptive reconfiguration to product variation as a result. In this paper, the practical problems for realization of wireless transmission of power and information (WTPI) needed for the proposed ADMS are clarified, and the practical solutions to these problems are presented. Several industrial applications of the WTPI are also introduced.
Therapeutic goals for effective platelet inhibition: a consensus document. (2006)

Clopidogrel combined with aspirin is the mainstay of antiplatelet therapy for patients who present with acute coronary syndromes as well as following either bare metal or drug-eluting stent placement. Limitations of clopidogrel therapy include the relatively long time course required to achieve maximal inhibition of platelet aggregation, individual variability in response to its effect, the risk of bleeding during its administration, and the irreversible nature of P2Y12 receptor binding, which leads to a prolonged time course for recovery of platelet function following discontinuation of clopidogrel. Several investigational P2Y12 receptor antagonists have pharmacological properties that may overcome some or all of these limitations. These novel agents such as prasugrel, AZD6140, and cangrelor are in advanced stages of clinical development for potential use in patients with coronary artery disease.
Optimizing distributions over molecular space. An Objective-Reinforced Generative Adversarial Network for Inverse-design Chemistry (ORGANIC) (2017)

Molecular discovery seeks to generate chemical species tailored to very specific needs. In this paper, we present ORGANIC, a framework based on Objective-Reinforced Generative Adversarial Networks (ORGAN), capable of producing a distribution over molecular space that matches with a certain set of desirable metrics. This methodology combines two successful techniques from the machine learning community: a Generative Adversarial Network (GAN), to create non-repetitive sensible molecular species, and Reinforcement Learning (RL), to bias this generative distribution towards certain attributes. We explore several applications, from optimization of random physicochemical properties to candidates for drug discovery and organic photovoltaic material design.
<title>New approach to 3-D registration of multimodality medical images by surface matching</title> (1992)

Multimodality images obtained from medical imaging systems such as computed tomography (CT), magnetic resonance (MR) imaging, positron emission tomography (PET), and single photon emission computed tomography (SPECT), generally provide complementary characteristic and diagnostic information. Synthesis of these image data sets into a single composite image containing these complementary attributes in accurate registration and congruence would provide truly synergistic information about the object(s) under examination. We have developed a new method which produces such correlation using parametric Chamfer matching. The method is fast, accurate, and reproducible. Surfaces ar initially extracted from two different images to be matched using semi-automatic segmentation techniques. These surfaces are represented as contours with common features to be matched. A distance transformation is performed for one surface image, and a cost function for the matching process is developed using the distance image. The geometric transformation includes three- dimensional translation, rotation, and scaling to accommodate images of different position, orientation, and size. The matching process involves searching this multi-parameter space to find the best fit which minimizes the cost function. The local minima problem is addressed by using a large number of starting points. A pyramid multi-resolution approach is employed to speed up both the distance transformation and the multi-parameter minimization processes. Robustness in noise handling is accomplished using multiple thresholds embedded in the multi- resolution search. The algorithm can register both partially overlapped and fragmented surfaces. Manual intervention is generally not necessary. Preliminary results suggest registration accuracy on the order of the voxel size used in the registration process. Computational time scales with the number of matching elements used, with about five minutes typical for 256<SUP>3</SUP> images using a modern desktop workstation.
Personalized Diabetes Management Using Electronic Medical Records (2016)

A personalized approach to diabetes management yielded substantial improvements in HbA<sub>1c</sub> outcomes relative to the standard of care. Our prototyped dashboard visualizing the recommendation algorithm can be used by providers to inform diabetes care and improve outcomes.
Improved Expression of a Hybrid Streptomyces clavuligerus cefE Gene in Penicillium chrysogenum (1994)

A hybrid cefE gene, encoding penicillin N expandase, was constructed by fusing the promoter sequences, Pcp, and terminator sequences, Pct from the Penicillium chrysogenum pcbC gene to the open reading frame (orf), cefEorf, from the Streptomyces clavuligerus cefE gene. The resulting hybrid gene, Pcp/cefE'orf/Pct, differed from a previously reported hybrid cefE gene contained on plasmid pPS65. The latter gene, Pcp/cefE'orf/Sct, contained the Pcp sequences fused to the S. clavuligerus cefE orf still attached to the S. clavuligerus terminator sequences, Sct. The new hybrid gene was transformed into P. chrysogenum on plasmid vector pRH6. Transformants were selected by phleomycin resistance conferred by a hybrid ble gene present on plasmid pRH6. The hybrid ble gene was formed by attaching Pcp sequences to the ble orf. Among transformants obtained with pRH6, one exhibited a 70-fold higher level of activity of penicillin N expandase than the best transformant previously obtained from a 10-fold larger population of pPS65 transformants. The penicillin N expandase activity in pRH6 transformant, 9EN-5-1, was fourfold higher than the activity in the S. clavuligerus strain used as the source of the cefE orf and 75% of the activity observed in an industrial strain of Cephalosporium acremonium. Sequencing of the junctions of the heterologous DNA in Pcp/cefEorf/Pct uncovered a modification of the cefE open reading frame introduced during construction of the hybrid gene; the modified open reading frame is designated cefE'orf.
A semi-digital DLL with unlimited phase shift capability and 0.08-400 MHz operating range (2002)

The DLL consists of two loops. The core loop is a first order DLL generating six edges evenly spaced by 30/spl deg/. The peripheral digital loop selects a pair of edges, /spl phi/ and /spl psi/, to interpolate. To cover the 360/spl deg/ desired range, the edges can be selectively inverted. The resulting edges, /spl phi/' and /spl psi/', drive a digitally-controlled interpolator that generates the main clock /spl Theta/. The interpolator quantization step is 2/spl deg/, i.e. 22ps for a 250MHz clock. This dual-loop architecture provides unlimited phase shift capability eliminating start-up issues and phase relationship constraints. The only requirement is that the DLL input clock and the reference clock are plesiochronous making this architecture suitable for clock-recovery applications.
Identification of the active-site lysine residues of two biosynthetic 3-dehydroquinases (1991)

The lysine residues involved in Schiff-base formation at the active sites of both the 3-dehydroquinase component of the pentafunctional arom enzyme of Neurospora crassa and of the monofunctional 3-dehydroquinase of Escherichia coli were labelled by treatment with 3-dehydroquinate in the presence of NaB3H4. Radioactive peptides were isolated by h.p.l.c. following digestion with CNBr (and in one case after further digestion with trypsin). The sequence established for the N. crassa peptide was ALQHGDVVKLVVGAR, and that for the E. coli peptide was QSFDADIPKIA. An amended nucleotide sequence for the E. coli gene (aroD) that encode 3-dehydroquinase is also presented, along with a revised alignment of the deduced amino acid sequences for the biosynthetic enzymes.
Ras Mediates the Activation of Phospholipase D by v-Src (1995)

We demonstrated previously that v-Src activates a phospholipase D (PLD) activity (Song, J., Pfeffer, L.M., and Foster, D.A. (1991) Mol. Cell. Biol. 11, 4903-4908) and that this activation is dependent upon a G protein(s) (Jiang H., Alexandropoulos, K., Song, J., and Foster, D.A. (1994) Mol. Cell. Biol. 14, 3676-3682). An in vitro PLD assay was developed to study G protein involvement in v-Src-induced PLD activity. Maximal PLD activity in membranes isolated from v-Src-transformed cells was dependent upon both GTP and cytosol. In this report, we present three lines of evidence demonstrating that v-Src-induced PLD activity is mediated by Ras. First, a neutralizing Ras monoclonal antibody (Y13-259) inhibits PLD activity in membranes isolated from v-Src-transformed Balb/c 3T3 cells. Second, immobilized Ras protein depleted cytosol of the ability to stimulate PLD activity. This effect was dependent upon preloading immobilized Ras with GTP. Last, expression of a dominant negative Ras mutant in v-Src-transformed cells reduced PLD activity to the level observed in the nontransformed parental cells. These data establish a novel role for Ras in the regulation of PLD activity.
Metal-Organic Frameworks Based on Trigonal Prismatic Building Blocks and the New “acs” Topology (2005)

Cationic and mixed-valent forms of Fe3O(CO2)6 trigonal prismatic clusters have been linked by ditopic links, namely, 1,4-benzenedicarboxylate (1,4-BDC) and 1,3-benzenedicarboxylate (1,3-BDC), to produce two 3-periodic metal-organic frameworks (MOFs), [Fe3O(1,4-BDC)3 (DMF)3][FeCl4] x (DMF)3 (MOF-235) and Fe3O(1,3-BDC)3 (py)3 x (py)0.5(H2O)1.5 (MOF-236) (DMF = N,N-dimethylformamide, py = pyridine), respectively. These MOFs exemplify a new, high-symmetry topology termed acs which we identify here as the default arrangement for linking trigonal prisms together.
Mathematical Modeling of Irreversible Electroporation for Treatment Planning (2007)

Irreversible Electroporation (IRE) is a new drug-free method to ablate undesirable tissue of particular use in cancer therapy. IRE achieves cell death within the targeted tissue through a series of electric pulses that elevate the transmembrane potentials to an extent that permanently damages the lipid bilayers throughout the treated region. Although the IRE procedure is easy to perform, treatment planning is complicated by the fact that the electric field distribution within the tissue, the greatest single factor controlling the extents of IRE, depends non-trivially on the electrode configuration, pulse parameters and any tissue heterogeneities. To address this difficulty, we instruct on how to properly model IRE and discuss the benefit of modeling in designing treatment protocols. The necessary theoretical basis is introduced and discussed through the detailed analysis of two classic dual-electrode configurations from electrochemotherapy: coaxial disk electrodes and parallel needle electrodes. Dimensionless figures for these cases are also provided that allow cell constants, treated areas, and the details of heating to be determined for a wide range of conditions, for uniform tissues, simply by plugging in the appropriate physical property values and pulse parameters such as electrode spacing, size, and pulse amplitude. Complexities, such as heterogeneous tissues and changes in conductivity due to electroporation, are also discussed. The synthesis of these details can be used directly by surgeons in treatment planning. Irreversible electroporation is a promising new technique to treat cancer in a targeted manner without the use of drugs; however, it does require a detailed understanding of how electric currents flow within biological tissues. By providing the understanding and tools necessary to design an IRE protocol, this study seeks to facilitate the translation of this new and exciting cancer therapy into clinical practice.