gebhart/patrepeval huggingface dataset:
P‐49: Design of Digital Time‐Modulation Pixel Memory Circuit on Glass Substrate for Low Power Application (2011)

Abstract A digital time‐modulation pixel memory circuit on glass substrate has been designed and verified in a 3‐μm low temperature poly‐silicon (LTPS) technology. The proposed circuit can generate 4‐bit digital codes and the corresponding inversion data by time‐modulation technique to refresh the static image without activating the data driver circuit. Therefore, the data driver of liquid crystal display (LCD) panel is not required to provide the image data of the frame by the proposed circuit while the LCD panel operates in the still mode. The power consumption from data driver can be further reduced in the LCD panel.
Phase I study of the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of the poly(ADP-ribose) polymerase (PARP) inhibitor veliparib (ABT-888; V) in combination with irinotecan (CPT-11; Ir) in patients (pts) with advanced solid tumors. (2011)

3000 Background: The nuclear enzyme PARP is essential in recognition and repair of DNA damage. In preclinical models, PARP inhibitors work as sensitizing agents for DNA-damaging agents such as Ir. V is an orally bioavailable PARP 1 and 2 inhibitor. This phase I study determined the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), PK and PD of V together with Ir. Methods: Eligibility included patients with performance status 0-2; ≥ age 18; adequate bone marrow, hepatic and renal function. Cycles were 21 days. Ir was given i.v. 100 mg/m2 over 90 min on Days 1 and 8. Twice daily (BID) oral dosing of V (10-50mg) occurred Days 3-14 (Cycle 1) and Days -1-14 (subsequent cycles) followed by a 6-day rest. PK studies were conducted with both agents alone and in combination. Tumor biopsies and matched peripheral blood mononuclear cells (PBMCs) were collected for PD evaluation of PAR, γ-H2AX, PARP1, TOPO1, and ERCC1 after Ir alone and after the combination. Results: 32 pts were treated (2 lung, 14 breast, 4 esophageal, 7 ovarian, 4 colon, 1 anal). Median age was 53 (range 31-73). Most frequent drug-related toxicities included: diarrhea (59%), nausea (56%), leucopenia (50%), fatigue (47%), neutropenia (47%), anemia (34%), and vomiting (31%). DLTs included fatigue, diarrhea, febrile neutropenia (gr 3), leukopenia and, neutropenia (gr 4). Response has been determined for 28 pts. A clinical benefit (CB) rate of 61% (5 PR, 2 MR, 10 SD) was observed. V exhibited linear PK over the dose range of 10 to 50 mg BID; co-administration of Ir did not affect PK of V. Exploratory analysis of pre/post-V treatment changes indicated median ERCC1 levels in tumor tissue and PBMCs differed somewhat by CB status. PAR levels in paired tumor biopsies showed > 50% reduction in 17 of 19 pts and > 90% reduction in 10 of 19 pts. Conclusions: The MTD and recommended phase II dose was established as 100 mg/m2 of Ir given i.v. Days 1 and 8 combined with 40 mg of V given BID 15 days on/6 days off (21 day cycle). Exploratory analysis demonstrated that V reduced PAR levels in tumor. Support: NCI U01-CA062487 and NCI R21-CA135572.
Mature Follicular Dendritic Cell Networks Depend on Expression of Lymphotoxin β Receptor by Radioresistant Stromal Cells and of Lymphotoxin β and Tumor Necrosis Factor by B Cells (1999)

The formation of germinal centers (GCs) represents a crucial step in the humoral immune response. Recent studies using gene-targeted mice have revealed that the cytokines tumor necrosis factor (TNF), lymphotoxin (LT) alpha, and LTbeta, as well as their receptors TNF receptor p55 (TNFRp55) and LTbetaR play essential roles in the development of GCs. To establish in which cell types expression of LTbetaR, LTbeta, and TNF is required for GC formation, LTbetaR-/-, LTbeta-/-, TNF-/-, B cell-deficient (BCR-/-), and wild-type mice were used to generate reciprocal or mixed bone marrow (BM) chimeric mice. GCs, herein defined as peanut agglutinin-binding (PNA+) clusters of centroblasts/centrocytes in association with follicular dendritic cell (FDC) networks, were not detectable in LTbetaR-/- hosts after transfer of wild-type BM. In contrast, the GC reaction was restored in LTbeta-/- hosts reconstituted with either wild-type or LTbetaR-/- BM. In BCR-/- recipients reconstituted with compound LTbeta-/-/BCR-/- or TNF-/-/BCR-/- BM grafts, PNA+ cell clusters formed in splenic follicles, but associated FDC networks were strongly reduced or absent. Thus, development of splenic FDC networks depends on expression of LTbeta and TNF by B lymphocytes and LTbetaR by radioresistant stromal cells.
Mechanism of Reduced Flavin Transfer from Vibrio harveyi NADPH−FMN Oxidoreductase to Luciferase (1998)

The mechanisms of reduced flavin transfer in biological systems are poorly understood at the present. The Vibrio harveyi NADPH-FMN oxidoreductase (FRP) and the luciferase pair were chosen as a model for the delineation of the reduced flavin transfer mechanism. FRP, which uses FMN as a cofactor to mediate the reduction of the flavin substrate by NADPH, exhibited a ping-pong kinetic pattern with a Km, FMN of 8 microM and a Km,NADPH of 20 microM in a single-enzyme spectrophotometric assay monitoring the NADPH oxidation. However, the kinetic mechanism of FRP was changed to a sequential pattern with a Km,FMN of 0.3 microM and a Km,NADPH of 0.02 microM in a luciferase-coupled assay measuring light emission. In contrast, the Photobacterium fischeri NAD(P)H-FMN oxidoreductase FRG showed the same ping-pong mechanism in both the single-enzyme spectrophotometric and the luciferase-coupled assays. Moreover, for the FRP, FMN at concentrations over 2 microM significantly inhibited the coupled reaction in both light intensity and quantum yield, and showed apparent noncompetitive and competitive inhibition patterns against NADPH and luciferase, respectively. No inhibition of the NADPH oxidation was detected under identical conditions. These results are consistent with a scheme that the reduced flavin cofactor of FRP is preferentially utilized by luciferase for light emission, the reduced flavin product generated by the reductase is primarily channeled into a dark oxidation, and luciferase competes against flavin substrate in reacting with the FRP reduced flavin cofactor. An FRP derivative containing 2-thioFMN as the cofactor was also used to further examine the mechanism of flavin transfer. Results again indicate a preferential utilization of the reductase reduced flavin cofactor by luciferase for the bioluminescence reaction.
Panel Causality of Regional Tourism Development and Economic Growth in China (2015)

The purpose of this study is to investigate the causality of regional tourism contribution and regional economic growth in China and to suggest policies for governments in allocating the economic resources. This study examined the causal relationship between regional economic growth and regional tourism development in China by employing annual data of 28 provinces in China from 1978 to 2008. A three-step procedures is used: panel unit root tests of Levin, Lin, and Chu (2002) and Im, Pesaran, and Shin (2003), a panel residual cointegration test proposed by Pedroni (1999), and the Granger non-causality test for heterogeneous panel data developed by Dumitrescu and Hurlin (2012). The results of the empirical analyses indicate a unidirectional causality from regional economic growth to regional tourism development in China. Thus, the evidence from this study supports the regional growth-led tourism hypothesis in China, thereby suggesting that regional economic growth increases regional tourism development in China. The findings of this study lead to the suggestion that policymakers invest in regional tourism development to meet economic growth goals because regional economic growth in the Chinese Provinces can be a useful policy to boost regional tourism development. Therefore, sustainable long-term regional economic growth can contribute to the potential of regional tourism development.
Maatschappelijk verantwoord ondernemerschap in internationale productketens (2005)

"Neem vanaf 1 januari 2006 alleen nog maar speelgoed af van fabrikanten&#13;\ndie het ethisch en humaan produceren". Zo luidt de oproep die is gedaan door de International Council of Toy Industries, een internationale belangenorganisatie van speelgoedproducenten met verenigingen in achttien landen. NRC 12-2-2005.&#13;\nBovenstaande krantenkop is geen uitzondering meer. Steeds vaker worden bedrijven aangesproken op hun maatschappelijke verantwoordelijkheid in de internationale productketen waarin zij werken. Wat zijn de ervaringen van bedrijven die deze ketenverantwoordelijkheid op zich nemen?
Activated gelatinase-B (MMP-9) and urokinase-type plasminogen activator in synovial fluids of patients with arthritis. Correlation with clinical and experimental variables of inflammation. (1995)

Our data suggest that the presence of gelatinase-B is a reflection of the inflammatory condition of the joints of patients with arthritis, and that the activation of gelatinase-B in the joints, which may occur in a u-PA/plasmin dependent and/or a stromelysin dependent way, contributes to the progression of arthritis.
Update on treatment of lysosomal storage diseases. (2007)

Lysosomal storage diseases (LSDs) are a large group of disorders caused by a deficiency of specific enzymes responsible for the degradation of substances present in lysosomes. In the past few years, treatments for LSDs were non specific and could only cope with signs and symptoms of the diseases. A successful therapeutic approach to LSDs should instead address to the underlying causes of the diseases, thus helping the degradation of the accumulated metabolites in the various organs, and at the same time preventing their further deposition. One way is to see to an available source of the deficient enzyme: bone marrow transplantation, enzyme replacement therapy and gene therapy are based on this rationale. The purpose of substrate reduction therapy is to down regulate the formation of the lysosomal substance to a rate at which the residual enzyme activity can catabolize the stored and de novo produced lysosomal substrate. Chemical chaperone therapy is based on small molecules able to bind and stabilize the misfolded enzymes. This paper offers a historical overview on the therapeutic strategies for LSDs.
Evaluating Treatment Efficacy in a Mouse Model of Enterovirus D68–Associated Paralytic Myelitis (2017)

Results in this model of EV-D68-associated AFM provide a rational basis for selecting empirical therapy in humans and establish this model as a useful system for evaluating other potential therapies.
Compartmentalization of Mammalian Folate-Mediated One-Carbon Metabolism (2010)

The recognition that mitochondria participate in folate-mediated one-carbon metabolism grew out of pioneering work beginning in the 1950s from the laboratories of D.M. Greenberg, C.G. Mackenzie, and G. Kikuchi. These studies revealed mitochondria as the site of oxidation of one-carbon donors such as serine, glycine, sarcosine, and dimethylglycine. Subsequent work from these laboratories and others demonstrated the participation of folate coenzymes and folate-dependent enzymes in these mitochondrial processes. Biochemical and molecular genetic approaches in the 1980s and 1990s identified many of the enzymes involved and revealed an interdependence of cytoplasmic and mitochondrial one-carbon metabolism. These studies led to the development of a model of eukaryotic one-carbon metabolism that comprises parallel cytosolic and mitochondrial pathways, connected by one-carbon donors such as serine, glycine, and formate. Sequencing of the human and other mammalian genomes has facilitated identification of the enzymes that participate in this intercompartmental one-carbon metabolism, and animal models are beginning to clarify the roles of the cytoplasmic and mitochondrial isozymes of these enzymes. Identifying the mitochondrial transporters for the one-carbon donors and elucidating how flux through these pathways is controlled are two areas ripe for exploration.
Evaluation of Hydroxyethylcellulose as a Hydrophilic Swellable Material for Delayed-Release Tablets. (1995)

Delayed-release tablets of diltiazem hydrochloride (DIL) were prepared by using AL-15 type hydroxyethycellulose(HEC) as a matrix material. The tablet consisted of a core tablet containing 30 mg of DIL and an outer shell formed by compressing HEC. The lag time to start the rapid release of DIL was more prolonged in the tablets consisting of a smaller particle size (20-53 and 53-106 μm) of HEC than those of the larger particle size(106-250 and 250-355 μm). However, there was little difference in the release rate of DIL among the two kinds of tablets. The rate of water uptake was greater in the tablets prepared with the larger particle size than those with the smaller particle size. These results suggest that the rate of water uptake seems to be a rate limiting process in setting the lag time. Observation of the surface of the tablets by electron micrograph showed that with the larger the particle size the cavity grows larger and with the smaller the particle size the cavity grows smaller.The lag time was also prolonged with an increase in the amount of HEC. Consequently, the lag time can be controlled optionally by changing the particle size and/or the amount of HEC forming the outer shell. This delayed-release system using HEC will be useful for time-related symptoms which need time-controlled or site-specific delivery in the gastrointestinal tract.
Human Macula Investigated In Vivo with Polarization-Sensitive Optical Coherence Tomography (2006)

PS-OCT represents a powerful tool for increasing image contrast in ocular tissues. The observed polarization-scrambling nature of the RPE may be used in diseased eyes to locate the RPE or remains of the RPE definitively in OCT images.
为电视台摄制的影片:产业运作、文化形式,大众观念 (1997)

为电视台摄制的影片：产业运作、文化形式，大众观念〔美国〕Ｌ．舒尔策李小刚译李恒基校电视片这一称谓一出现就因受到批评界广泛而激烈的抵制而显得特别引人注目。尽管ＮＢＣ（全国广播公司）１９６６年摄制的《声誉是游戏之名》（通常被认为是第一部电视片），收视率...
Advances on chimeric antigen receptor-modified T-cell therapy for oncotherapy (2018)

Tumor treatment is still complicated in the field of medicine. Tumor immunotherapy has been the most interesting research field in cancer therapy. Application of chimeric antigen receptor T (CAR-T) cell therapy has recently achieved excellent clinical outcome in patients, especially those with CD19-positive hematologic malignancies. This phenomenon has induced intense interest to develop CAR-T cell therapy for cancer, especially for solid tumors. However, the performance of CAR-T cell treatment in solid tumor is not as satisfactory as that in hematologic disease. Clinical studies on some neoplasms, such as glioblastoma, ovarian cancer, and cholangiocarcinoma, have achieved desirable outcome. This review describes the history and evolution of CAR-T, generalizes the structure and preparation of CAR-T, and summarizes the latest advances on CAR-T cell therapy in different tumor types. The last section presents the current challenges and prospects of CAR-T application to provide guidance for subsequent research.
Disruption of the Epilepsy KCNQ2 Gene Results in Neural Hyperexcitability (2000)

Benign familial neonatal convulsion (BFNC) is a common idiopathic epilepsy with autosomal dominant inheritance. Recently, two novel voltage-dependent potassium channel genes, KCNQ2 and KCNQ3, were identified by positional cloning as being responsible for BFNC. Heterotetramers of the products of these genes form M-channels and regulate the threshold of electrical excitability of neurons. We disrupted the mouse KCNQ2 gene via gene targeting to study the relationship between KCNQ2 and epilepsy. Homozygous pups (KCNQ2 -/-) died within a few hours after birth owing to pulmonary atelectasis that was not due to the status of epileptic seizures, although their development was morphologically normal. Heterozygous mice had decreased expression of KCNQ2 and showed hypersensitivity to pentylenetetrazole, an inducer of seizure. These data indicate that the decreased expression of KCNQ2 might cause a hyperexcitability of the CNS, which accounts for the mechanism of BFNC.
THE HYALURONIDASE OF BRAIN (1972)

Abstract— Hyaluronidase (hyaluronate glycanohydrolase, EC 3.2.1.35), with a pH optimum of 3.7, was detected in rat and bovine brain. It degraded hyaluronic acid and, at a slower rate, chondroitin sulphate to a mixture of higher oligosaccharides with N‐acetylhexosamine at the reducing end. The enzyme was enriched 5‐ and 6‐fold in a crude lysosomal fraction of rat brain or bovine cerebral cortex, and was further purified to a total enrichment of 9‐fold by ammonium sulphate fractionation. The enzyme activity in grey matter was more than twice that found in white matter, and there was no significant change in enzyme activity as a function of increasing age from the neonatal to the adult rat brain. The level of hyaluronidase activity in rat brain is considerably greaterthan that required to account for the rate of catabolism of hyaluronic acid and chondroitin sulphate measured in vivo.
Subsite interactions of ribonuclease T1: viscosity effects indicate that the rate-limiting step of GpN transesterification depends on the nature of N (1991)

We report on the effect of the viscogenic agents glycerol and ficoll on the RNase T1 catalyzed turnover of GpA, GpC, GpU, and Torula yeast RNA. For wild-type enzyme, we find that the kcat/Km values for the transesterification of GpC and GpA as well as for the cleavage of RNA are inversely proportional to the relative viscosity of glycerol-containing buffers; no such effect is observed for the conversion of GpU to cGMP and U. The second-order rate constants for His40Ala and Glu46Ala RNase T1, two mutants with a drastically reduced kcat/km ratio, are independent of the microviscosity, indicating that glycerol does not affect the intrinsic kinetic parameters. Consistent with the notion that molecular diffusion rates are unaffected by polymeric viscogens, addition of ficoll has no effect on the kcat/Km for GpC transesterification by wild-type enzyme. The data indicate that the second-order rate constants for GpC, GpA, and Torula yeast RNA are at least partly limited by the diffusion-controlled association rate of substrate and active site; RNase T1 obeys Briggs-Haldane kinetics for these substrates (Km greater than Ks). Calculations suggest that the equilibrium dissociation constants (Ks) for the various GpN-wild-type enzyme complexes are virtually independent of N whereas the measured kcat values follow the order GpC greater than GpA greater than GpU. This is also revealed by the steady-state kinetic parameters of Tyr38Phe and His40Ala RNase T1, two mutants that follow simple Michaelis-Menten kinetics because of a dramatically reduced kcat value (i.e., Km = Ks).(ABSTRACT TRUNCATED AT 250 WORDS)
Human leukocyte elastase and cathepsin G are specific inhibitors of C5a‐dependent neutrophil enzyme release and chemotaxis (2004)

Circulating human neutrophils from patients with severe inflammatory disorders such as erysipelas and sepsis are specifically desensitized to complement factor C5a stimulation but not to stimulation with other stimuli like N-formyl-methionyl-leucyl-phenylalanine (FMLP), interleukin-8 (IL-8), leukotriene B4 (LTB4), or platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine). In this study, we raised the question whether factors released from polymorphonuclear leukocytes (PMNs) can specifically down-regulate C5a-dependent neutrophil functions. When neutrophils were preincubated with either neutrophil lysates or neutrophil degranulation supernatants, a complete inhibition of C5a-stimulated beta-glucuronidase release and chemotaxis could be observed, whereas FMLP-, IL-8-, LTB4- or PAF-dependent functions were not affected. Serine protease inhibitors like phenylmethylsulfonyl fluoride, antileukoprotease, or elafin abolished this effect. High-performance liquid chromatography of neutrophil degranulation supernatants revealed pronounced inhibition of C5a-dependent neutrophil functions in fractions exerting elastase or cathepsin G activity, but not in fractions exerting proteinase 3 activity. Using purified human leukocyte elastase (HLE), C5a responses like intracellular calcium influx, beta-glucuronidase release, and chemotaxis were also specifically inhibited. Our experiments show that the release of HLE or cathepsin G from neutrophils specifically down-regulates the responsiveness of neutrophils to C5a. Elastase and cathepsin G may therefore play an important role in the down-regulation of acute inflammation.
Nucleic Acid Aptamer‐Mediated Drug Delivery for Targeted Cancer Therapy (2014)

Aptamers are emerging as promising therapeutic agents and recognition elements. In particular, cell-SELEX (systematic evolution of ligands by exponential enrichment) allows in vitro selection of aptamers selective to whole cells without prior knowledge of the molecular signatures on the cell surface. The advantage of aptamers is their high affinitiy and binding specificity towards the target. This Minireview focuses on single-stranded (ss) oligonucleotide (DNA or RNA)-based aptamers as cancer therapeutics/theranostics. Specifically, aptamer-nanomaterial conjugates, aptamer-drug conjugates, targeted phototherapy and targeted biotherapy are covered in detail. In reviewing the literature, the potential of aptamers as delivery systems for therapeutic and imaging applications in cancer is clear, however, major challenges remain to be resolved, such as the poorly understood pharmacokinetics, toxicity and off-target effects, before they can be fully exploited in a clinical setting.
Centrosomes, microtubules, and microfilaments in the reendothelialization and remodeling of double-sided in vitro wounds. (1992)

The maintenance of endothelial monolayer integrity is an important function of aortic endothelial cells. Our study was designed to test two hypotheses related to the repair of the wounded endothelial monolayer. First, that the reappearance of the highly ordered cobblestone monolayer after wound closure is associated with specific sequential changes in the cytoskeletal system. Second, that there are different patterns of reendothelialization depending on whether microfilaments or microtubules are disrupted. One and a half millimeter wide wounds were created down the middle of confluent endothelial monolayers so that there were two wound edges facing each other. During the initiation of repair, the centrosomes of the cells on both sides of the wound reorientated to the front of the cell. The dense peripheral band of actin microfilaments disappeared, the cells elongated and migrated as a uniform sheet with wound closure occurring within 60 hours. The rate of closure remained constant until the migrating fronts met. The cytoskeletal changes observed and the rate of closure were similar to those we reported in a single edge wound. At closure, however, there was a transient piling up of cells which disappeared after 24 to 36 hours. Within 36 to 48 hours after closure, the centrosomes became randomly distributed around the nucleus. By 40 to 48 hours, the dense peripheral band started to reappear and the cells returned to a cobblestone appearance 72 to 96 hours after closure. Thus, the remodeling of the confluent monolayer after wound closure occurs in association with a specific series of cytoskeletal changes. When the microfilaments were disrupted with cytochalasin B, cell migration still occurred but it took up to four times longer for closure. These cells were initially flatter than normal and contained only a few microfilament fibers; however, the microtubule system was intact and centrosome reorientation occurred, but at a slower rate. However, when the microtubules were disrupted with colchicine, either at the onset of wounding or during repair, neither centrosome reorientation nor cell migration occurred. Thus wound closure of small-sized wounds require the presence of intact microtubules, whereas the additional presence of microfilaments results in a more rapid and efficient system of reendothelialzation.