gebhart/patrepeval huggingface dataset:
Malic Enzyme of Escherichia coli (1969)

Abstract A kinetic study of partially purified malic enzyme from Escherichia coli was made. The double reciprocal initial velocity plots of both of the substrates, TPN+ and malate, were linear in the absence of allosteric inhibitors (oxalacetate, acetyl coenzyme A, and DPNH). Product inhibition studies with bicarbonate and pyruvate gave generally only linear inhibitions with either TPN+ or malate as varied substrates. With TPNH as the inhibitor, however, the initial velocity plots for malate became nonlinear. This nonlinearity vanished when assays were performed in the presence of 0.72 m glycine, a reagent which desensitizes the enzyme to various allosteric effectors. In the presence of this desensitizing agent TPNH gave linear noncompetitive inhibition against TPN+ as the varied substrate. From these studies it was postulated that malic enzyme followed an ordered mechanism with isomerization of the free enzyme as an obligate step of the reaction pathway. In the presence of each of the allosteric inhibitors, the initial velocity plots for TPN+ remained linear but the plots for malate became nonlinear. Inhibition by acetyl-CoA and oxalacetate was competitive with malate, but noncompetitive with TPN+. The kinetic behavior of malic enzyme in the presence of allosteric inhibitors was analyzed in terms of a two conformational state model and the conclusions reached were (a) that the E-TPN+ complex existed in the absence of allosteric ligands in a form which had a high affinity for malate (State R) and (b) that the binding of any one of the several inhibitors to the enzyme resulted in its conversion to a state (T) which had very little affinity for malate.
BaMAP: A Broadband Multimedia Application Platform (2003)

In this paper, a broadband multimedia application platform, BaMAP, is introduced. The BaMAP arms to offer content and service providers a good integrated environment for efficient content production, management, delivery and sharing. It supports large-scale hierarchical storage, as well as mechanisms for content distribution and queries from remote nodes. The on-demand service, part of the BaMAP, offers two access interfaces, DVB-C and IP, which allow the platform to run on most of the existing access networks.
The effect of antibiotics on methicillin-resistant Staphylococcus aureus (2007)

Antimicrobial drugs encourage the overgrowth of organisms resistant to the agents used. Acquisition and subsequent overgrowth of methicillin-resistant Staphylococcus aureus (MRSA) are particularly associated with beta-lactam antibiotics and quinolones. These drugs allow rapid proliferation of an organism that might have been merely colonizing the skin, leading to clinical infection, treatment difficulties and potential transmission to others. In addition, there is increasing evidence that inappropriate antibiotics not only encourage overgrowth with MRSA but may also enhance pathogenicity. Such virulence is not necessarily due to simple expansion of MRSA across skin and mucosal surfaces; there appear to be molecular changes that facilitate mechanisms such as quorum sensing, adhesion, phage mobilization, exotoxin production, intracellular persistence and biofilm formation, all of which contribute towards more severe infection. This review examines the association between MRSA and certain classes of antibiotics and explores the molecular mechanisms underlying a perceived increase in virulence following inappropriate therapy. It is possible that empirical prescribing has a significant impact on the management of MRSA infections and ultimately patient outcome. It is time to challenge the prescribers' right to prescribe what they like, when they like, for patients at risk of MRSA.
E6AP/UBE3A Ubiquitin Ligase Harbors Two E2∼ubiquitin Binding Sites (2013)

By exploiting (125)I-polyubiquitin chain formation as a functional readout of enzyme activity, we have quantitatively examined the mechanism of human E6AP/UBE3A for the first time. Initial rate studies identify UbcH7 as the cognate E2 carrier protein for E6AP, although related Ubc5 isoforms and the ISG15-specific UbcH8 paralog also support E6AP with reduced efficacy due to impaired binding and catalytic competence. Initial rates of polyubiquitin chain formation displayed hyperbolic kinetics with respect to UbcH7 concentration (K(m) = 57.6 ± 5.7 nM and kcat = 0.032 ± 0.001 s(-1)) and substrate inhibition above 2 μM. Competitive inhibition by an isosteric UbcH7C86S-ubiquitin oxyester substrate analog (K(i) = 64 ± 18 nM) demonstrates that Km reflects intrinsic substrate affinity. In contrast, noncompetitive inhibition by a UbcH7C86A product analog (K(i) = 7 ± 0.7 μM) and substrate inhibition at high concentrations require two functionally distinct E2∼ubiquitin substrate binding sites. The kinetics of polyubiquitin chain formation reflect binding at a cryptic Site 1 not previously recognized that catalyzes E6AP∼ubiquitin thioester formation. Subsequent binding of E2∼ubiquitin at the canonical Site 2 present in the extant crystal structure is responsible for polyubiquitin chain elongation. Other rate studies show that the conserved -4 Phe(849) residue is required for polyubiquitin chain formation rather than target protein conjugation as originally suggested. The present studies unambiguously preclude earlier models for the mechanism of Hect domain-catalyzed conjugation through the canonical binding site suggested by the crystal structure and define a novel two-step mechanism for formation of the polyubiquitin degradation signal.
<title>Off-axial HMD optical system consisting of aspherical surfaces without rotational symmetry</title> (1996)

An off-axial optical system is desirable for a see-through head mounted display (HMD) with a wide field of view (FOV). Using our new off-axial paraxial theory and the fabricating methods, we have achieved to correct the off-axial aberrations of the optical systems which consists of an aspherical surfaces without rotational symmetry. In this paper, we describe 3 types of off-axial HMD optical systems. (1) The first one is a hologram for a monochromatic HMD. The hologram has been recorded the wavefront generated by computer generated hologram. The image spot size is about 15 micrometers over 9 degree FOV. (2) The second one is an aspherical mirror system for a color HMD. The designed image spot size is less than 30 micrometers over 43.5 degree FOV. The shape error of the fabricated mirror is measured by a contact probing from 1.0 micrometers to 1.9 micrometers . The maximum resolution is 36 lp/mm. (3) The last one is a prism with aspherical surfaces, 34 degree FOV and less than 15 mm thickness. The monocular HMD with only 80 g weight has been developed. The line of sight detecting device has been applied as an interactive man-machine interface.
Foundations of Image Science (2005)

The <i>Journal of Electronic Imaging</i> (JEI), copublished bimonthly with the Society for Imaging Science and Technology, publishes peer-reviewed papers that cover research and applications in all areas of electronic imaging science and technology.
Deletion of antigen-specific immature thymocytes by dendritic cells requires LFA-1/ICAM interactions (1992)

An in vitro assay was used for assessing the participation of various cell surface molecules and the efficacy of various cell types in the deletion of Ag-specific immature thymocytes. Thymocytes from mice expressing a transgenic TCR specific for the male Ag presented by the H-2Db class I MHC molecule were used as a target for deletion. In H-2d transgenic mice, cells bearing the transgenic TCR are not subjected to thymic selection as a consequence of the absence of the restricting H-2Db molecule but, nevertheless, express this TCR on the vast majority of immature CD4+8+ thymocytes. In this report we show that CD4+8+ thymocytes from H-2d TCR-transgenic mice are preferentially killed upon in vitro culture with male APC; DC were particularly effective in mediating in vitro deletion when compared with either B cells or T cells. Deletion of CD4+8+ thymocytes by DC was H-2b restricted and could be inhibited by mAb to either LFA-1 alpha or CD8. Partial inhibition was observed with mAb to ICAM-1, whereas mAb to CD4 and LFA-1 beta were without effect. These results are the first direct evidence of LFA-1 involvement in negative selection and provide further direct support for the participation of CD8/class I MHC interactions in this process. Like the requirements for deletion, activation of mature male-specific CD4-8+ T cells from female H-2b TCR-transgenic mice was also largely dependent on Ag presentation by DC and required both LFA-1/ICAM and CD8/class I MHC interactions; these results support the view that activation and deletion may represent maturation stage-dependent consequences of T cells encountering the same APC. Finally, our results also support the hypothesis that negative selection (deletion) does not require previous positive selection because deletion was observed under conditions where positive selection had not occurred.
Recombinant antibodies for the selective targeting of tumor neovasculature. (2002)

Angiogenesis, the sprouting of new blood vessels from preexisting ones, is a characteristic feature of many aggressive solid tumors. Advances in the identification of markers of angiogenesis and new methodologies for the production of human recombinant antibodies are making it possible to deliver bioactive molecules to the tumor neovasculature in a selective fashion. This review illustrates how recombinant antibody derivatives may open new avenues for the imaging and therapy of angiogenesis-related diseases, such as cancer, blinding ocular disorders and rheumatoid arthritis.
Regulated intratumoral expression of IL-12 using a RheoSwitch Therapeutic System® (RTS®) gene switch as gene therapy for the treatment of glioma (2018)

The purpose of this study was to determine if localized delivery of IL-12 encoded by a replication-incompetent adenoviral vector engineered to express IL-12 via a RheoSwitch Therapeutic System<sup>®</sup> (RTS<sup>®</sup>) gene switch (Ad-RTS-IL-12) administered intratumorally which is inducibly controlled by the oral activator veledimex is an effective approach for glioma therapy. Mice bearing 5-10-day-old intracranial GL-261 gliomas were intratumorally administered Ad-RTS-mIL-12 in which IL-12 protein expression is tightly controlled by the activator ligand, veledimex. Local tumor viral vector levels concomitant with veledimex levels, IL-12-mRNA expression, local and systemic cytokine expression, tumor and systemic flow cytometry and overall survival were studied. Ad-RTS-mIL-12+veledimex elicited a dose-related increase in tumor IL-12 mRNA and IL-12 protein and discontinuation of veledimex resulted in a return to baseline levels. These changes correlated with local immune and antitumor responses. Veledimex crossed the blood-brain barrier in both orthotopic GL-261 mice and cynomolgus monkeys. We have demonstrated that this therapy induced localized controlled production of IL-12 which correlates with an increase in tumor-infiltrating lymphocytes (TILs) leading to the desired biologic response of tumor growth inhibition and regression. At day 85 (study termination), 65% of the animals that received veledimex at 10 or 30 mg/m<sup>2</sup>/day were alive and tumor free. In contrast, the median survival for the other groups were: vehicle 23 days, bevacizumab 20 days, temozolomide 33 days and anti-PD-1 37 days. These findings suggest that the controlled intratumoral production of IL-12 induces local immune cell infiltration and improved survival in glioma, thereby demonstrating that this novel regulated immunotherapeutic approach may be an effective form of therapy for glioma.
Prehospital administration of freeze-dried plasma, is it the solution for trauma casualties? (2017)

Retrospective case series study, level IV.
Sonic hedgehog protein signals not as a hydrolytic enzyme but as an apparent ligand for Patched (1999)

The amino-terminal signaling domain of the Sonic hedgehog secreted protein (Shh-N), which derives from the Shh precursor through an autoprocessing reaction mediated by the carboxyl-terminal domain, executes multiple functions in embryonic tissue patterning, including induction of ventral and suppression of dorsal cell types in the developing neural tube. An apparent catalytic site within Shh-N is suggested by structural homology to a bacterial carboxypeptidase. We demonstrate here that alteration of residues presumed to be critical for a hydrolytic activity does not cause a loss of inductive activity, thus ruling out catalysis by Shh-N as a requirement for signaling. We favor the alternative, that Shh-N functions primarily as a ligand for the putative receptor Patched (Ptc). This possibility is supported by new evidence for direct binding of Shh-N to Ptc and by a strong correlation between the affinity of Ptc-binding and the signaling potency of Shh-N protein variants carrying alterations of conserved residues in a particular region of the protein surface. These results together suggest that direct Shh-N binding to Ptc is a critical event in transduction of the Shh-N signal.
Molecular Mechanisms of Cellular Cholesterol Efflux (2014)

Most types of cells in the body do not express the capability of catabolizing cholesterol, so cholesterol efflux is essential for homeostasis. For instance, macrophages possess four pathways for exporting free (unesterified) cholesterol to extracellular high density lipoprotein (HDL). The passive processes include simple diffusion via the aqueous phase and facilitated diffusion mediated by scavenger receptor class B, type 1 (SR-BI). Active pathways are mediated by the ATP-binding cassette (ABC) transporters ABCA1 and ABCG1, which are membrane lipid translocases. The efflux of cellular phospholipid and free cholesterol to apolipoprotein A-I promoted by ABCA1 is essential for HDL biogenesis. Current understanding of the molecular mechanisms involved in these four efflux pathways is presented in this minireview.
Primary Structure of the Human Proenkephalin Gene (1983)

The nucleotide sequence of a 6.8-kb region of human DNA containing the proenkephalin gene and flanking regions is reported. The gene consists of four exons separated by three introns and spans approximately 5.3 kb of DNA. Location and identification of several repetitive DNA sequences within and flanking the gene are also described. The distribution of CpG dinucleotides as well as the extent of CpG methylation at several restriction sites within and surrounding the gene is also presented. The structural organization of the human proenkephalin gene exhibits striking similarities to the organization of the human pro-opiomelanocortin (POMC) gene. Nucleotide sequence homologies suggest that two opioid peptide precursors, proenkephalin and prodynorphin, may have arisen by duplication from a common ancestral gene.
Single-walled carbon nanotube electronics (2002)

Single-walled carbon nanotubes (SWNTs) have emerged as a very promising new class of electronic materials. The fabrication and electronic properties of devices based on individual SWNTs are reviewed. Both metallic and semiconducting SWNTs are found to possess electrical characteristics that compare favorably to the best electronic materials available. Manufacturability issues, however, remain a major challenge.
Improved wireless location accuracy using antenna arrays and interference cancellation (2004)

Location finding for CDMA subscribers using an antenna array at the base station is studied. Two methods are considered for radio location that are based on time of arrival (TOA) and angle of arrival (AOA) measurements. For TOA estimates, a maximum likelihood algorithm and a practical structure are proposed when an antenna array is available. For AOA estimates, a least-squares (LS) algorithm is used. The LS module is combined with a multiple access interference (MAI) cancellation technique to improve the AOA estimation accuracy in multiuser multipath scenarios.
Synthesis and Antihistaminic H1 Activity of 1,2,5(6)-Trisubstituted Benzimidazoles (1999)

A number of benzimidazoles, having several substituents on the azoIe and benzene nudei and C-2 (methylamino, ethylenediamine, morpholine, piperazine and piperidine) were prepared.Regioselective synthesis was designed for the N'-alkyl substituted benzimidazoles (14-15).X-Ray structure analysis of (14) was also revealed.Compounds were evaluated for their in vitro HI-antihistaminic activity in the isolated guinea-pig ileum method.The compound (11) exhibits best activity.Classical HI--antihistaminic compounds have been usehl for the treatment of allergic diseases.Unfortunately, because of their depressive effects such as sedation and hypnosis on the central nervous system and peripheral side effects there is a limitation for the use of them.'During the last decade considerable efforts have been spent for discovering a new antihistaminic agent with minimum CNS effects while retaining a potent antihistaminic activity.It is getting more important day by day, because of the increasing ratio of the allergic disease particularly in developed ~ountries.~In previous ~t u d i e s ~, ~ we reported the synthesis and biological evaluation of 1,2,5(6)-aisubstituted benzimidazoles as an antimicrobial agents.Continuing our interest in this field, we found some papers concerning the synthesis and sbucture activity relationships of 2-(4-substituted l-piperazinyl)benzimidazoles, which have potent HI-antihistaminic Among the synthesized compounds, l-(2-ethoxyethyl)-2-(4-methyl-l-homopiperazinyl)benzimidazole (KB-2413) 0 was 39 times more potent than chlorpheniramine maleate in H~antihistaminic activity in vivo launched in Japan in 1994, for the treatment of allergic rhinitis and urticaria, named as Emedastine Drfumarate.'
Metoclopramide treatment of tardive dyskinesia (1981)

Five patients with tardive dyskinesia (average age, 64 years) were treated with a central dopamine blocking agent, metoclopramide hydrochloride. The duration of symptoms ranged from four to 30 months. A pretreatment disability score was graded (0 to 4) for buccolingual, extremity, and truncal movements and for duration of tongue protrusion. A 59% improvement was achieved in total disability scores. Tongue protrusion demonstrated the most noticeable improvement. The average daily dosage ranged from a minimum of 20 mg to a maximum of 80 mg given in divided doses. Duration of follow-up ranged from three to eight months. Preliminary data suggest that metoclopramide may be effective in the treatment of tardive dyskinesia. (<i>JAMA</i>1981;246:1934-1935)
The inhibitory effects of berry polyphenols on digestive enzymes (2005)

The evidence for the effect of polyphenol components of berries on digestive enzymes is reviewed. Anthocyanins inhibit alpha-glucosidase activity and can reduce blood glucose levels after starch-rich meals, a proven clinical therapy for controlling type II diabetes. Ellagitannins inhibit alpha-amylase activity and there is potential for synergistic effects on starch degradation after ingestion of berries such as raspberries and strawberries, which contain substantial amounts of ellagitannins and anthocyanins. A range of berry polyphenols (e.g. flavonols, anthocyanidins, ellagitannins and proanthocyanidins) can inhibit protease activities at levels which could affect protein digestion in the gastrointestinal tract. In contrast, potential for the inhibition of gastrointestinal lipase activity, a proven therapeutic target for the control of obesity through reduced fat digestion, may be limited to proanthocyanidins. Taking into account the manifold possible synergies for inhibition of starch, protein and/or lipid digestion by the spectrum of polyphenol components present within berry species, the inhibition of digestive enzymes by dietary polyphenols may represent an under-reported mechanism for delivering some of the health benefits attributed to a diet rich in fruit and vegetables.
Nonvolatile Memory and Programmable Logic from Molecule-Gated Nanowires (2002)

Bistable nanoscale switches have been assembled using nanowires and redox active molecules as building blocks. The nanodevices consist of nanowire field-effect transistors (NW-FET) functionalized with redox active molecules, where the redox species can store charges and thereby maintain the NW-FETs in either a logic on or off state with high or low channel conductance, respectively. Single NW and crossed NW-FET devices have been assembled and shown to switch reversibly as two- and three-terminal devices. Individual NW devices with on/off ratios exceeding 104 and retention times in excess of 20 min, and integrated arrays in which devices are independently addressable, have been assembled. The characteristics of the molecule-gated NW-FET devices suggest that they could serve as key elements in a range of nanoelectronics applications, including nonvolatile memory and programmable logic array.
Variability of gene expression profiles in human blood and lymphoblastoid cell lines (2010)

Readily accessible samples such as peripheral blood or cell lines are increasingly being used in large cohorts to characterise gene expression differences between a patient group and healthy controls. However, cell and RNA isolation procedures and the variety of cell types that make up whole blood can affect gene expression measurements. We therefore systematically investigated global gene expression profiles in peripheral blood from six individuals collected during two visits by comparing five of the following cell and RNA isolation methods: whole blood (PAXgene), peripheral blood mononuclear cells (PBMCs), lymphoblastoid cell lines (LCLs), CD19 and CD20 specific B-cell subsets. Gene expression measurements were clearly discriminated by isolation method although the reproducibility was high for all methods (range ρ = 0.90-1.00). The PAXgene samples showed a decrease in the number of expressed genes (P < 1*10-16) with higher variability (P < 1*10-16) compared to the other methods. Differentially expressed probes between PAXgene and PBMCs were correlated with the number of monocytes, lymphocytes, neutrophils or erythrocytes. The correlations (ρ = 0.83; ρ = 0.79) of the expression levels of detected probes between LCLs and B-cell subsets were much lower compared to the two B-cell isolation methods (ρ = 0.98). Gene ontology analysis of detected genes showed that genes involved in inflammatory responses are enriched in B-cells CD19 and CD20 whereas genes involved in alcohol metabolic process and the cell cycle were enriched in LCLs. Gene expression profiles in blood-based samples are strongly dependent on the predominant constituent cell type(s) and RNA isolation method. It is crucial to understand the differences and variability of gene expression measurements between cell and RNA isolation procedures, and their relevance to disease processes, before application in large clinical studies.
Novel 3-dimensional Dual Control-gate with Surrounding Floating-gate (DC-SF) NAND flash cell for 1Tb file storage application (2010)

A novel 3-dimensional Dual Control-gate with Surrounding Floating-gate (DC-SF) NAND flash cell has been successfully developed, for the first time. The DC-SF cell consists of a surrounding floating gate with stacked dual control gate. With this structure, high coupling ratio, low voltage cell operation (program: 15V and erase: -11V), and wide P/E window (9.2V) can be obtained. Moreover, negligible FG-FG interference (12mV/V) is achieved due to the control gate shield effect. Then we propose 3D DC-SF NAND flash cell as the most promising candidate for 1Tb and beyond with stacked multi bit FG cell (2 ~ 4bit/cell).