gebhart/patrepeval huggingface dataset:
Levodopa-Carbidopa Intestinal Gel Pharmacokinetics: Lower Variability than Oral Levodopa-Carbidopa (2017)

In a double-blind, double-dummy, double-titration Phase 3 trial in advanced Parkinson's disease (PD) patients, the efficacy and safety of Levodopa-carbidopa intestinal gel (LCIG) infusion were characterized relative to immediate-release oral levodopa-carbidopa (LC-oral) treatment. We present in this report the comparative pharmacokinetic profiles of LCIG and LC-oral from this pivotal study. The results presented in this report clearly demonstrate that LCIG results in lower variability and fluctuations in levodopa and carbidopa plasma concentrations compared to LC-oral. The superior pharmacokinetic profiles with LCIG were consistent with its improved efficacy compared to LC-oral as demonstrated in this study.
Development of a cellobiose dehydrogenase modified electrode for amperometric detection of diphenols (1999)

A new amperometric biosensor based on cellobiose dehydrogenase (CDH) was created for the detection of ortho- and para-diphenolic compounds. The developed electrode efficiently discriminates between diphenolic and monophenolic compounds. The analyte, a diphenolic compound, is oxidised on the surface of a graphite electrode at an applied potential of +300 mV vs. Ag/AgCl. The diphenol is then regenerated by the adsorbed CDH in the presence of cellobiose, thus allowing an amplified response signal. Different parameters of the CDH–electrode system were optimised, e.g., applied potential, immobilisation time, flow rate, substrate concentration and storage conditions. Using the optimised parameters the sensitivity and detection limits for various diphenolic compounds were evaluated, resulting in detection limits below 5 nM for most of the compounds tested. The highest sensitivity recorded was obtained for dopamine, 3.6 A l mol–1 cm–2. The operational stability of the electrodes was high: during 2 h of continuous operation only a 1–2% decrease in response signal was observed.
Albinterferon alfa-2b, a novel fusion protein of human albumin and human interferon alfa-2b, for chronic hepatitis C (2009)

Albinterferon alfa-2b exhibits high antiviral activity, and appears to offer safety/tolerability comparable to the current standard of care, and health-related quality-of-life benefits in patients with CHC. Its ability to maintain drug concentrations above the 90% effective concentration over prolonged dosing intervals suggests that it may be an ideal partner for combination therapy with direct antiviral agents in CHC. The results of the phase 3 trials are eagerly anticipated as they should greatly clarify the future role of alb-IFN in the treatment of CHC.
Transcriptional silencing of Ty1 elements in the RDN1 locus of yeast. (1997)

We demonstrate that in Saccharomyces cerevisiae, the tandem array of ribosomal RNA genes (RDN1) is a target for integration of the Ty1 retrotransposon that results in silencing of Ty1 transcription and transposition. Ty1 elements transpose into random rDNA repeat units and are mitotically stable. In addition, we have found that mutation of several putative modifiers of RDN1 chromatin structure abolishes silencing of Ty1 elements in the rDNA array. Disruption of SIR2, which elevates recombination in RDN1, or TOP1, which increases psoralen accessibility in rDNA, or HTA1-HTB1, which reduces histone H2A-H2B levels and causes localized chromatin perturbations, abolishes transcriptional silencing of Ty1 elements in RDN1. Furthermore, deletion of the gene for the ubiquitin conjugating enzyme Ubc2p, which ubiquitinates histones in vitro, derepresses not only Ty1 transcription but also mitotic recombination in RDN1. On the basis of these results, we propose that a specialized chromatin structure exists in RDN1 that silences transcription of the Ty1 retrotransposon.
Physiological Effects of Food Carbohydrates (1975)

A symposium co-sponsored by the Division of Carbohydrate Chemistry and the Division of Agricultural and Food Chemistry at the 168th meeting of the American Chemical Society, Atlantic City, N.J., Sept. 11-12, 1974.
Functional and nonfunctional mutations distinguished by random recombination of homologous genes (1997)

We describe a convenient method for distinguishing functional from nonfunctional or deleterious mutations in homologous genes. High fidelity in vitro gene recombination ("DNA shuffling") coupled with sequence analysis of a small sampling of the shuffled library exhibiting the evolved behavior allows identification of those mutations responsible for the behavior in a background of neutral and deleterious mutations. Functional mutations are expected to occur in 100% of the sequenced screened sample; neutral mutations are found in 50% on average, and deleterious mutations do not appear at all. When used to analyze 10 mutations in a laboratory-evolved gene encoding a thermostable subtilisin E, this method rapidly identified the two responsible for the observed protease thermostability; the remaining eight were neutral with respect to thermostability, within the precision of the screening assay. A similar approach, coupled with selection for growth and survival of the host organism, could be used to distinguish adaptive from neutral mutations.
A novel booster plate technology in high density NAND flash memories for voltage scaling-down and zero program disturbance (2002)

The booster plate in NAND flash memory cells gives numerous advantages: the reduction of program, erase and pass voltages, zero program disturbance and increased cell current. At the same time, it is simple to integrate the technology to the conventional fabrication processes. It is expected that the booster plate technology will become one of the key technologies for achieving high density memories such as 256 Mbit and 1 Gbit NAND flash.
Data Logic Structure and Key Technologies on Intelligent High-precision Map (2020)

Taking autonomous driving and driverless as the research object, we discuss and define intelligent high-precision map. Intelligent high-precision map is considered as a key link of future travel, a carrier of real-time perception of traffic resources in the entire space-time range, and the criterion for the operation and control of the whole process of the vehicle. As a new form of map, it has distinctive features in terms of cartography theory and application requirements compared with traditional navigation electronic maps. Thus, it is necessary to analyze and discuss its key features and problems to promote the development of research and application of intelligent high-precision map. Accordingly, we propose an information transmission model based on the cartography theory and combine the wheeled robot’s control flow in practical application. Next, we put forward the data logic structure of intelligent high-precision map, and analyze its application in autonomous driving. Then, we summarize the computing mode of &#x0201C;Crowdsourcing+Edge-Cloud Collaborative Computing&#x0201D;, and carry out key technical analysis on how to improve the quality of crowdsourced data. We also analyze the effective application scenarios of intelligent high-precision map in the future. Finally, we present some thoughts and suggestions for the future development of this field.
지방자치단체의 정보보호 현황 및 인식의 변화 분석 (2016)

정보화 수준이 향상됨에 따라 각종 사건들이 증가하면서 정보보호에 대한 중요성 또한 강조되어 왔다. 그동안 정부가 지속적인 노력을 기울여 왔음에도 불구하고 정보보호 관련 사건들은 증가하고 있는 것이 현실이다. 따라서 이 연구는 정부기관 중에서 시민들과 가장 먼저 접촉하는 지방자치단체를 중심으로 정부기관의 정보보호 현실에 있어서 이와 같은 모순적 상황이 발생하는 원인을 확인해 보고자 하였다. 이를 위해 정보보호와 관련한 기존의 연구결과를 토대로 정보보호와 관련한 제도, 예산·인력, 그리고 담당공무원의 인식을 중심으로 그동안 변화가 어떻게 이루어졌는지를 분석하였다. 분석결과, 중앙정부차원의 제도 및 예산의 변화를 확인할 수 있었다. 그러나 지방자치단체의 변화는 미미했으며, 담당공무원들의 정보보호에 대한 인식도 큰 변화가 없는 것으로 나타났다.
Chiral Cooperativity in Diastereomeric Diphosphite Ligands:  Effects on the Rhodium-Catalyzed Enantioselective Hydroformylation of Styrene (1997)

Diastereomeric diphosphites (L∩L = 3−8) have been synthesized from enantiomerically pure pentane-2,4-diol and axially chiral 3,3‘-bis(trialkylsilyl)-2,2‘-bisphenol phosphorochloridites and 3,3‘-bis(trialkylsilyl)-2,2‘-bisnaphthol phosphorochloridites. These diphosphites have been used to test the influence of chiral cooperativity in the rhodium-catalyzed asymmetric hydroformylation of styrene. Systematic variation in chirality at both the chiral ligand bridge and the axially chiral biphenyl and binaphthyl substituents revealed a remarkable effect on the selectivity of the hydroformylation catalysts. For the atropisomeric bisnaphthol-based diphosphites, cooperative effects were observed in the asymmetric hydroformylation of styrene. High enantioselectivities (87%) and regioselectivities up to 95% for 2-phenylpropanal were found under mild reaction conditions (15−50 °C, 20 bar of syn gas CO−H2 [1:1]) for the ligand derived from (2R,4R)-pentane-2,4-diol and (S)-bisnaphthol. The same high enantiomeric excess was observed for the free-rotating bisphenol-substituted ligands. The highest selectivity was obtained with trimethylsilyl substituents at the ortho position. The solution structures of the active catalysts [HRhL∩L(CO)2 complexes (L∩L = 3−8)], have been studied by 31P and 1H NMR spectroscopy at variable temperature (313−213 K). Spectroscopic data, in combination with the obtained results in catalysis, suggest that diphosphite ligands (L∩L) containing the conformationally flexible axially chiral biphenyl moieties predominantly exist as single atropisomers in the HRhL∩L(CO)2 complexes. Comparison of the bisphenol and bisnaphthol substituents suggests that the high enantiomeric excesses obtained with the former are caused by the preferential formation of the most selective diastereomer.
Structural requirements for the extracellular interaction of plasminogen activator inhibitor 1 with endothelial cell matrix-associated vitronectin. (1990)

The interaction of plasminogen activator inhibitor-1 (PAI-1) with its binding protein vitronectin (VN) (Declerck, P. J., De Mol, M., Alessi, M.-C., Baudner, S., Paques, E.-P., Preissner, K. T., Müller-Berghaus, G., and Collen, D. (1988) J. Biol. Chem. 263, 15454-15461) in the extracellular matrix (ECM) of cultured human endothelial cells (HUVEC) was studied. Like PAI-1, VN was found associated with the ECM as evidenced by direct antibody binding, by Western blot analysis as well as by diffuse immunofluorescence staining in permeabilized HUVEC. The specific interaction of VN with confluent monolayers of HUVEC was found to be saturable within 2-4 h at 37 degrees C only with respect to binding to the cells, while no saturable binding to the underlying ECM was observed, indicating that the majority if not all ECM-associated VN was derived from the culture medium. In contrast to PAI-1, ECM-associated VN was resistant toward glycine (pH 2.3), guanidine or urokinase treatment, suggesting that VN was tightly associated with the ECM network. Binding of recombinant PAI-1 (rPAI-1) was largely blocked by anti-VN IgG and only partly by anti-collagen IgG but not by antibodies against other ECM components, indicating that VN constitutes the primary binding protein for ECM-associated PAI-1. This contention was supported by ligand blotting experiments in which rPAI-1 was reacted with nitrocellulose replicas of electrophoretically separated ECM components. Protein band(s) (Mr = 63,000-67,000), comigrating with bovine VN (i.e. medium-derived VN) rather than with human VN were identified as major binding component(s). Moreover, binding studies with purified components revealed that PAI-1 did not show any affinity for collagen (type I/III) alone, whereas VN collagen coating was a much better template for PAI-1 binding than VN alone and that conformationally extended VN provides maximal PAI-1 binding capacity. Binding of rPAI-1 to surface-coated VN was saturable and revealed that (unlike urokinase) heparin or the synthetic peptide Gly-Arg-Gly-Asp-Ser did not inhibit PAI-1 binding. Ligand binding of rPAI-1 to nitrocellulose replicas from sodium dodecyl sulfate-polyacrylamide gels containing electrophoretically separated peptides from VN digests documented the association of PAI-1 with Mr = 10,000-20,000 fragments originating from the heparin-binding domain of VN. These results indicate that the exposure of the glycosaminoglycan-binding domain in VN may allow the concomitant binding of PAI-1 and heparin-like molecules to this region of the VN molecule.(ABSTRACT TRUNCATED AT 400 WORDS)
Antibodies as antigens. The use of mouse monoclonal antibodies to focus human T cells against selected targets. (1988)

We found that three tumor patients treated with mouse mAbs have T cells that recognize processed mouse Ig on autologous APC in a class II-restricted fashion, and we have shown that mouse mAbs directed against various cell surface molecules can be used as antigens to focus these T cells on an MHC class II-positive target of choice.
Spatial and temporal evolution of hemorrhage in the hyperacute phase of experimental spinal cord injury: In vivo magnetic resonance imaging (2000)

To follow the spatial and temporal evolution of hemorrhage, in vivo MRI studies of experimental spinal cord injury (SCI) were performed on 17 rats in the very acute phase (hyperacute), starting as early as 9 min and continued up to 400 min posttrauma. Axial MR images were processed slice by slice over a 21 mm length around the epicenter of the injury. The data were analyzed statistically and fitted to an empirically derived function to characterize the spatial and temporal evolution of hemorrhage. The results indicated that 1) the initial hemorrhage in the very early phase of the injury area covered 12.5% of the total cord area and subsequently increased with a time constant of 700 min, 2) a major portion of the hemorrhage was concentrated spatially within the 4 mm distance from the epicenter, 3) the volume of hemorrhage normalized to its initial value increased linearly at a rate of approximately 0.0015 min(-1), and 4) edema was observed at the gray- and white-matter junction as early as 12 min postinjury. In general, edema appeared to be focal and scattered in this phase of the injury, which made its quantification unreliable on MRI.
Abstract 2332: Oncogenic MYD88 mutants require Toll-like receptors. (2013)

Abstract Oncogenic mutations affecting the signaling adapter MyD88 are present in 39% of activated B-cell-like (ABC) diffuse large B cell lymphomas (DLBCLs), with the most recurrent MyD88 mutant, L265P, present in 29% of cases. MYD88 mutations constitutively activate multiple signaling cascades that promote the survival and proliferation of ABC DLBCLs, including the NF-B, type-1 interferon, p38 and JAK/STAT pathways. It is unknown whether MyD88 mutants act autonomously or require a receptor to engage these downstream pathways. Here we show that the MyD88 L265P oncoprotein binds constitutively to two members of the Toll-like receptor family, TLR7 and TLR9, thereby amplifying signals that emanate from these receptors. Knockdown of TLR7 or TLR9 potently suppressed NF-B activity in ABC DLBCL cell lines and promoted apoptosis. Depletion of known proteins essential for TLR7 and TLR9 trafficking and signaling, including UNC93B1, PRAT4A or CD14, was lethal for ABC DLBCL lines. Similarly, pharmacologic inhibition of TLR7 and TLR9 function in lysosomal compartments using the cathepsin inhibitor zFA-fmk or hydroxychloroquine diminished MyD88 signaling and reduced survival of ABC DLBCL lines. TLR7 or TLR9 mutants that are defective in ligand binding failed to promote the survival of ABC DLBCL lines following knockdown of endogenous TLR7 or TLR9 expression in ABC DLBCL lines. Moreover, an inhibitory oligonucleotide capable of suppressing TLR9 responses in normal B cells blocked NF-B signaling and survival of ABC DLBCL lines. These new insights into the oncogenic mechanisms of MyD88 mutants provide a rationale for targeting of TLR7 and TLR9 signaling for the therapy of ABC DLBCL. Citation Format: Kian-Huat Lim, Gregory M. Barton, Louis M. Staudt. Oncogenic MYD88 mutants require Toll-like receptors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2332. doi:10.1158/1538-7445.AM2013-2332
Clinical Risk Factors and CT Imaging Features of Carotid Atherosclerotic Plaques as Predictors of New Incident Carotid Ischemic Stroke: A Retrospective Cohort Study (2012)

Our new paradigm of using age ≥ 75 years, history of hypertension, and carotid maximal wall thickness of >4 mm identified most of the patients with subsequent new carotid stroke in our study. It is simple and may help clinicians choose the patients at greatest risk of developing a carotid infarct, warranting validation with a prospective observational study.
Carbohydrate-Deficient Glycoprotein Syndrome - A Fourth Subtype (1995)

Two infants are described, who, we suggest, represent a fourth subtype of carbohydrate-deficient glycoprotein (CDG) syndrome. Both patients showed microcephaly and severe epilepsy with absent psychomotor development and similar minor dysmorphic features. There were no signs of liver dysfunction. Several glycoproteins in blood, including transferrin, alpha 1-antitrypsin, antithrombin and thyroxine-binding globulin, demonstrated abnormal isoforms suggesting a partial deficiency of mainly one or two sialic acid residues. Both the clinical picture and the glycoprotein abnormalities were different from previously defined types of CDG syndrome.
Cloning and expression profiling of small RNAs expressed in the mouse ovary (2007)

Small noncoding RNAs have been suggested to play important roles in the regulation of gene expression across all species from plants to humans. To identify small RNAs expressed by the ovary, we generated mouse ovarian small RNA complementary DNA (srcDNA) libraries and sequenced 800 srcDNA clones. We identified 236 small RNAs including 122 microRNAs (miRNAs), 79 piwi-interacting RNAs (piRNAs), and 35 small nucleolar RNAs (snoRNAs). Among these small RNAs, 15 miRNAs, 74 piRNAs, and 21 snoRNAs are novel. Approximately 70% of the ovarian piRNAs are encoded by multicopy genes located within the repetitive regions, resembling previously identified repeat-associated small interference RNAs (rasiRNAs), whereas the remaining approximately 30% of piRNA genes are located in nonrepetitive regions of the genome with characteristics similar to the majority of piRNAs originally cloned from the testis. Since these two types of piRNAs display different structural features, we categorized them into two classes: repeat-associated piRNAs (rapiRNAs, equivalent of the rasiRNAs) and non-repeat-associated piRNAs (napiRNAs). Expression profiling analyses revealed that ovarian miRNAs were either ubiquitously expressed in multiple tissues or preferentially expressed in a few tissues including the ovary. Ovaries appear to express more rapiRNAs than napiRNAs, and sequence analyses support that both may be generated through the "ping-pong" mechanism. Unique expression and structural features of these ovarian small noncoding RNAs suggest that they may play important roles in the control of folliculogenesis and female fertility.
Lattice Compression from Conduction Electrons in Heavily Doped Si:As (1988)

High-resolution x-ray scattering measurements on heavily doped Si:As (5\ifmmode\times\else\texttimes\fi{}${10}^{21}$ As ${\mathrm{cm}}^{\ensuremath{-}3}$) show lattice compression relative to pure silicon, $\frac{\ensuremath{\Delta}a}{a}=\ensuremath{-}0.0019\ifmmode\pm\else\textpm\fi{}0.0003$, although extended x-ray-absorption fine-structure measurements show that the As-Si bond length is 0.06\ifmmode\pm\else\textpm\fi{}0.02 \AA{} greater than the usual Si-Si bond length. The overall lattice compression is attributed to increased population of conduction-band states which reduces Si-Si bond lengths. These measurements provide the first direct measurement of the hydrostatic deformation potential for the conduction-band edge in silicon, +3.3\ifmmode\pm\else\textpm\fi{}0.7 eV.
Targeting transgene expression to antigen-presenting cells derived from lentivirus-transduced engrafting human hematopoietic stem/progenitor cells (2002)

Hematopoietic stem cells (HSCs) represent an important target for the treatment of various blood disorders. As the source of critical cells within the immune system, genetic modification of HSCs can also be used to modulate immune responses. The effectiveness of HSC-mediated gene therapy largely depends on efficient gene delivery into long-term repopulating progenitors and targeted transgene expression in an appropriate progeny of the transduced pluripotent HSCs. Self-inactivating (SIN) lentiviral vectors have been demonstrated to be capable of transducing mitotically inactive cells, including HSCs, and accommodating a nonviral promoter to control the transgene expression in transduced cells. In this study, we constructed 2 SIN lentiviral vectors, EF.GFP and DR.GFP, to express the green fluorescent protein (GFP) gene controlled solely by the promoter of either a housekeeping gene EF-1alpha or the human HLA-DRalpha gene, which is selectively expressed in antigen-presenting cells (APCs). We demonstrated that both vectors efficiently transduced human pluripotent CD34+ cells capable of engrafting nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. When the EF.GFP vector was used, constitutive high-level GFP expression was obtained in all the human HSC progeny detectable in NOD/SCID mice and in subsequent in vitro differentiation assays, indicating that engrafting human HSCs have been transduced. In contrast, the DR.GFP vector mediated transgene expression specifically in human HLA-DR+ cells and highly in differentiated dendritic cells (DCs), which are critical in regulating immunity. Furthermore, human DCs derived from transduced and engrafted human cells potently stimulated allogeneic T-cell proliferation. This study demonstrated successful targeting of transgene expression to APCs/DCs after stable gene transduction of pluripotent HSCs.
Thrombopoietin — Clinically Realized? (1997)

For approximately 30 years, hematologists have sought the humoral regulator of platelet production, thrombopoietin.1 Although a factor with the appropriate physiologic effects was partially purified, the goal continued to evade researchers until 1994, when three laboratories simultaneously reported that c-Mpl ligand had the characteristics of thrombopoietin.2 Synonyms for thrombopoietin in the literature are c-Mpl ligand, mpl ligand, megapoietin, and megakaryocyte growth and development factor (a truncated version of thrombopoietin).What explains the fact that thrombopoietin was ultimately purified and characterized by five laboratories almost simultaneously? In 1992, Wendling and colleagues described the c-mpl gene, the cellular homologue of v- . . .
Embedded SRAM and Cortex-M0 core with backup circuits using a 60-nm crystalline oxide semiconductor for power gating (2014)

A chip of embedded SRAM having backup circuits using a 60-nm c-axis aligned crystalline oxide semiconductor (CAAC-OS) such as CAAC indium-gallium-zinc oxide (CAAC-IGZO) and Cortex-M0 core having flip-flops with CAAC-OS backup circuits is fabricated. The SRAM and M0 core can retain data using the backup circuits during power-off; thus, they can perform power gating (PG) with backup time of 100 ns and recovery time of 10 clock cycles (including data restoration time (100 ns)). Further, memory cell area and performance in combining a 45-nm Si SRAM memory cell with 60-nm CAAC-OS are estimated to have negligible overhead.