gebhart/patrepeval huggingface dataset:
The retinoblastoma tumor suppressor controls androgen signaling and human prostate cancer progression (2010)

Retinoblastoma (RB; encoded by RB1) is a tumor suppressor that is frequently disrupted in tumorigenesis and acts in multiple cell types to suppress cell cycle progression. The role of RB in tumor progression, however, is poorly defined. Here, we have identified a critical role for RB in protecting against tumor progression through regulation of targets distinct from cell cycle control. In analyses of human prostate cancer samples, RB loss was infrequently observed in primary disease and was predominantly associated with transition to the incurable, castration-resistant state. Further analyses revealed that loss of the RB1 locus may be a major mechanism of RB disruption and that loss of RB function was associated with poor clinical outcome. Modeling of RB dysfunction in vitro and in vivo revealed that RB controlled nuclear receptor networks critical for tumor progression and that it did so via E2F transcription factor 1-mediated regulation of androgen receptor (AR) expression and output. Through this pathway, RB depletion induced unchecked AR activity that underpinned therapeutic bypass and tumor progression. In agreement with these findings, disruption of the RB/E2F/nuclear receptor axis was frequently observed in the transition to therapy resistance in human disease. Together, these data reveal what we believe to be a new paradigm for RB function in controlling prostate tumor progression and lethal tumor phenotypes.
The electrooxidation of small organic molecules on platinum nanoparticles supported on gold: influence of platinum deposition procedure (2007)

The electrocatalytic properties of small platinum nanoparticles were investigated for the oxidation of CO, methanol, and formic acid using voltammetry, chronoamperometry, and surface-enhanced Raman spectroscopy. The particles were generated by galvanostatic deposition of platinum on a polished gold surface from an H2PtCl6 containing electrolyte and ranged between 10 and 20 nm in diameter for low platinum surface concentrations, 10 and 120 nm for medium concentrations, and full Pt monolayers for high concentrations. CO stripping and bulk CO oxidation experiments on the particles up to 120 nm in diameter displayed pronounced structural effects. The CO oxidation current-time transients show a current decay for low platinum coverages and a current maximum for medium and high coverages. These results were also observed in the literature for particles of 2- to 5-nm size and agglomerates of these particles. The similarities between the literature and our results, despite large differences in particle size and morphology, suggest that particle structure and morphology are also very important catalytic parameters. Surface-enhanced Raman spectroscopy data obtained for the oxidation of CO on the Pt-modified Au electrodes corroborate this conclusion. A difference in the ratio between CO adsorbed in linear- and bridge-bonded positions on the Pt nanoparticles of different sizes demonstrates the influence of the surface morphology. The oxidation activity of methanol was found to decrease with the particle size, while the formic acid oxidation rate increases. Again, a structural effect is observed for particles of up to ca. 120 nm in diameter, which is much larger than the particles for which a particle size effect was reported in the literature. The particle shape effect for the methanol oxidation reaction can be explained by a reduction in available “ensemble sites” and a reduction in the mobility of CO formed by decomposition of methanol. As formic acid does not require Pt ensemble sites, decreasing the particle size, and thus, the relative number of defects, increases the reaction rate.
MicroRNAs miR‐96, miR‐124, and miR‐199a regulate gene expression in human bone marrow‐derived mesenchymal stem cells (2012)

MicroRNAs are small non-coding RNAs that control gene expression at the post-transcriptional level by binding to 3'-untranslated regions (3'-UTR) of their target mRNAs. They present a promising tool to delineate the molecular mechanisms regulating differentiation of human mesenchymal stromal cells (hMSCs) and to improve the controlled differentiation of hMSCs in therapeutic applications. Here we show that three microRNAs, miR-96, miR-124, and miR-199a, were differentially expressed during osteogenic, adipogenic, and chondrogenic induction of human bone marrow-derived MSCs. miR-96 expression was increased during osteogenesis and adipogenesis, but not during chondrogenesis. miR-124 was exclusively expressed in adipocytes, whereas miR-199a was upregulated in osteoblasts and chondrocytes. Furthermore, functional studies with synthetic miRNA precursors and inhibitors demonstrated that miR-96, miR-124, and miR-199a regulated the expression of genes important for hMSC differentiation, such as aggrecan, transcription factor SOX9, and fatty acid binding protein 4 (FABP4). Modulation of miR-96, miR-124, and miR-199a expression may thus be useful in specific targeting of hMSC differentiation, for e.g., MSC-based therapies. J
The Prevalence, Impact, and Treatment of Migraine and Severe Headaches in the U nited S tates: A Review of Statistics From National Surveillance Studies (2013)

This report provides the most current available estimates of the prevalence, impact, and treatment patterns of migraine or severe headache in the United States. Migraine and other severe headaches are a common and major public health problem, particularly among reproductive-aged women. Data about prevalence and disability from the major government-funded surveillance studies are generally consistent with results of studies such as the American Migraine Studies 1 and 2, and the AMPP study.
B3(Fv)-PE38KDEL, a single-chain immunotoxin that causes complete regression of a human carcinoma in mice. (1991)

The genes encoding the heavy- and light-chain Fv regions of the monoclonal murine antibody B3, which recognizes a carbohydrate antigen on the surface of many human carcinomas, were cloned by PCR techniques and used to generate single-chain immunotoxins containing Pseudomonas exotoxin (PE). The light and heavy chains were connected by a flexible linker to form a single-chain antigen-binding protein, B3(Fv), which was in turn fused to truncated forms of PE lacking the cell-binding domain. The single-chain Fv and two different B3(Fv) immunotoxins, B3(Fv)-PE40 and B3(Fv)-PE38KDEL, were expressed in Escherichia coli and the single-chain immunotoxins were purified to near homogeneity. Both recombinant immunotoxins were shown to be cytotoxic specifically to carcinoma cell lines that express the B3 antigen on their surface; B3(Fv)-PE38KDEL was significantly more active. Furthermore, intravenous administration of B3(Fv)-PE38KDEL caused complete regression of human epidermoid carcinomas growing subcutaneously in immunodeficient mice.
Effects of anolyte recirculation rates and catholytes on electricity generation in a litre-scale upflow microbial fuel cell (2010)

Microbial fuel cells (MFCs) are an attractive technology for simultaneous bioenergy recovery and organic removal; however, the lack of studies conducted with large-scale MFCs, especially those larger than 1 L, obstructs further development of this technology. In this paper, we built and operated a 4.9 L upflow microbial fuel cell (UMFC) with a liquid volume of 2.4 L. Its electricity generation and organic removal performance were examined under different operating conditions. The UMFC produced an open-circuit potential of 1.00 V with an acidified catholyte. Changing the recirculation of the anolyte did not significantly affect the power output in a short period, but a long-term test demonstrated improved electricity production at higher recirculation rates. The water produced via oxygen reduction or diffused from the anode was not sufficient for the cathode reaction; thus, an external supply of water is necessary. Lowering the pH of the catholyte benefited the cathode reaction and increased power production; however, pH is not the only factor affecting the cathode reaction and if organic matters were contained in the catholyte, for instance using the anode effluent as a catholyte, electricity generation decreased. The results and experiences gained from this study will help to further develop pilot-scale MFCs for practical applications.
4-band*4096-element Schottky-barrier infrared linear image sensor (1991)

A multispectral linear array has been developed for remote-sensing applications in the short-wavelength (SW) infrared (IR) band. The device is a monolithic quadruple-band image sensor, consisting of 4096 detectors for each band. The SW-IR sensor uses silicon Schottky-barrier (SB) infrared charge-coupled-device (IRCCD) technology. Platinum silicide SB detectors are used. They operate at cryogenic temperature and respond to the short- and middle-wavelength infrared regions. The package for the SW-IRCCD has also been developed. The package has a SiC-Al/sub 2/O/sub 3/-SiC structure. The performance of the device has been measured, and the device can be used in spaceborne applications.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The click modular router (2000)

Clicks is a new software architecture for building flexible and configurable routers. A Click router is assembled from packet processing modules called elements . Individual elements implement simple router functions like packet classification, queuing, scheduling, and interfacing with network devices. A router configurable is a directed graph with elements at the vertices; packets flow along the edges of the graph. Several features make individual elements more powerful and complex configurations easier to write, including pull connections, which model packet flow drivn by transmitting hardware devices, and flow-based router context, which helps an element locate other interesting elements. Click configurations are modular and easy to extend. A standards-compliant Click IP router has 16 elements on its forwarding path; some of its elements are also useful in Ethernet switches and IP tunnelling configurations. Extending the IP router to support dropping policies, fairness among flows, or Differentiated Services simply requires adding a couple of element at the right place. On conventional PC hardware, the Click IP router achieves a maximum loss-free forwarding rate of 333,000 64-byte packets per second, demonstrating that Click's modular and flexible architecture is compatible with good performance.
Error-Free 320-Gb/s All-Optical Wavelength Conversion Using a Single Semiconductor Optical Amplifier (2007)

We demonstrate error-free wavelength conversion at 320 Gb/s by employing a semiconductor optical amplifier that fully recovers in 56 ps. Error-free operation is achieved without using forward error correction technology. We employ optical filtering to select the blue sideband of the spectrum of the probe light, to utilize fast chirp dynamics introduced by the amplifier, and to overcome the slow gain recovery. This leads to an effective recovery time of less than 1.8 ps for the wavelength converter. The wavelength converter has a simple configuration and is implemented by using fiber-pigtailed components. The concept allows photonic integration
The Genetic Basis of Resistance to Anticoagulants in Rodents (2005)

Anticoagulant compounds, i.e., derivatives of either 4-hydroxycoumarin (e.g., warfarin, bromadiolone) or indane-1,3-dione (e.g., diphacinone, chlorophacinone), have been in worldwide use as rodenticides for >50 years. These compounds inhibit blood coagulation by repression of the vitamin K reductase reaction (VKOR). Anticoagulant-resistant rodent populations have been reported from many countries and pose a considerable problem for pest control. Resistance is transmitted as an autosomal dominant trait although, until recently, the basic genetic mutation was unknown. Here, we report on the identification of eight different mutations in the VKORC1 gene in resistant laboratory strains of brown rats and house mice and in wild-caught brown rats from various locations in Europe with five of these mutations affecting only two amino acids (Tyr139Cys, Tyr139Ser, Tyr139Phe and Leu128Gln, Leu128Ser). By recombinant expression of VKORC1 constructs in HEK293 cells we demonstrate that mutations at Tyr139 confer resistance to warfarin at variable degrees while the other mutations, in addition, dramatically reduce VKOR activity. Our data strongly argue for at least seven independent mutation events in brown rats and two in mice. They suggest that mutations in VKORC1 are the genetic basis of anticoagulant resistance in wild populations of rodents, although the mutations alone do not explain all aspects of resistance that have been reported. We hypothesize that these mutations, apart from generating structural changes in the VKORC1 protein, may induce compensatory mechanisms to maintain blood clotting. Our findings provide the basis for a DNA-based field monitoring of anticoagulant resistance in rodents.
Broad spectrum diffusion model for room acoustics ray-tracing algorithms (2000)

Geometrical acoustics methods have already been transformed to account for diffusely reflecting boundaries. In randomized ray-tracing algorithms, the sound rays are either specularly reflected or scattered, according to the value of a random number which is compared with the diffusion factor. However, this method becomes inefficient if this factor depends on frequency, since the process must then be repeated for each frequency band. A method is proposed in this paper to compute all frequency components simultaneously in a single pass. The diffuse reflection model is based on the definition of a new concept: the "splitting coefficient," which can differ from the diffusion factor. First, the randomized ray-tracing method is described and the diffusion model is applied to a single diffusing surface in free field. It is shown that the results computed by the program are in accordance with theoretical results. Then, the method is shown to work properly when it is applied to more realistic enclosures: This is proved in theory and illustrated by some examples. A particular problem is the increase of the statistical error which has been solved by an appropriate control of the splitting coefficient.
High Temperature Subatmospheric Chemical Vapor Deposited Undoped Silicate Glass: A Solution for Next Generation Shallow Trench Isolation (1999)

Undoped silicate glass deposited using the tetraethylorthosilicate (TEOS) and ozone thermal reaction has been selected as one of the candidates for shallow trench isolation applications. As a replacement for existing low pressure or atmospheric pressure chemical vapor deposition processes for device dimensions below 0.25 μm, TEOS/ozone films deposited at high temperature (>550°C) exhibit the superior qualities in terms of void‐free trench fill. In this paper, we present some characterization of the silicon oxide film deposited in the subatmospheric pressure regime using TEOS/ozone chemistry, aimed at developing a high‐quality dielectric film to meet shallow trench isolation gap‐fill requirements. It is also identified that low ozone/TEOS ratio reduces surface and pattern sensitivity. Therefore, no additional treatment or predeposition is necessary. Moreover, to enhance the etch resistance of the silicon oxide, the as‐deposited film is annealed at high temperature for densification and bond reconstruction. © 1999 The Electrochemical Society. All rights reserved.
The “Correctly Folded” State of Proteins: Is It a Metastable State? (2002)

Alzheimer's disease, type II diabetes, Creutzfeldt–Jakob disease, and amyloid-related diseases: In each of these pathological situations, well-folded proteins undergo an irreversible transition from the “correctly folded” state to a collapsed β-sheet-rich structure. Here it is suggested that the aggregated form represents a global minimum in Gibbs energy for ensembles of protein molecules in general, and that at an infinite time any protein solution above a critical concentration will eventually undergo structural transition into the aggregated state.
Single nucleotide polymorphism genotyping using short, fluorescently labeled locked nucleic acid (LNA) probes and fluorescence polarization detection (2002)

Locked nucleic acids (LNAs) are synthetic nucleic acid analogs that bind to complementary target molecules (DNA, RNA or LNA) with very high affinity. At the same time, this binding affinity is decreased substantially when the hybrids thus formed contain even a single mismatched base pair. We have exploited these properties of LNA probes to develop a new method for single nucleotide polymorphism genotyping. In this method, very short (hexamer or heptamer) LNA probes are labeled with either rhodamine or hexachlorofluorescein (HEX), and their hybridization to target DNAs is followed by measuring the fluorescence polarization (FP) of the dyes. The formation of perfectly complementary double-stranded hybrids gives rise to significant FP increases, whereas the presence of single mismatches results in very small or no changes of this parameter. Multiplexing of the assay can be achieved by using differentially labeled wild-type and mutant specific probes in the same solution. The method is homogeneous, and because of the use of extremely short LNA probes, the generation of a universal set of genotyping reagents is possible.
Sequences spanning the leader-repeat junction mediate CRISPR adaptation to phage in Streptococcus thermophilus (2015)

CRISPR-Cas systems are RNA-based immune systems that protect prokaryotes from invaders such as phages and plasmids. In adaptation, the initial phase of the immune response, short foreign DNA fragments are captured and integrated into host CRISPR loci to provide heritable defense against encountered foreign nucleic acids. Each CRISPR contains a ∼100-500 bp leader element that typically includes a transcription promoter, followed by an array of captured ∼35 bp sequences (spacers) sandwiched between copies of an identical ∼35 bp direct repeat sequence. New spacers are added immediately downstream of the leader. Here, we have analyzed adaptation to phage infection in Streptococcus thermophilus at the CRISPR1 locus to identify cis-acting elements essential for the process. We show that the leader and a single repeat of the CRISPR locus are sufficient for adaptation in this system. Moreover, we identified a leader sequence element capable of stimulating adaptation at a dormant repeat. We found that sequences within 10 bp of the site of integration, in both the leader and repeat of the CRISPR, are required for the process. Our results indicate that information at the CRISPR leader-repeat junction is critical for adaptation in this Type II-A system and likely other CRISPR-Cas systems.
Investigations on the role of flagella in the colonization of infant mice withCampylobacter jejuniand attachment ofCampylobacter jejunito human epithelial cell lines (1985)

The biochemical and biological properties of the flagella of Campylobacter jejuni have been investigated using two variants selected from a flagellate, motile clinical isolate (strain 81116): a flagellate, non-motile variant (SF-1) and an aflagellate variant (SF-2). Phenotypic and biochemical analysis of the strains and amino acid analysis of the isolated flagella suggest that the variants differed from the wild-type strain only in the absence of flagella and/or motility. The aflagellate variant poorly colonized the gastrointestinal tract of infant mice but the flagellate, non-motile variant colonized the mice as successfully as the wild-type strain. 35S-labelled organisms were used to investigate the attachment of the variants to human epithelial cell monolayers in vitro. The flagellate, non-motile strain attached more efficiently to the cells than the wild-type strain or the aflagellate strain. Differences in attachment suggest that an adhesin is intimately associated with flagella of C. jejuni and that active flagella mediate only a tenuous association with host cells. This adhesin attached most efficiently to cells of intestinal epithelial origin and was not specifically inhibited by various sugars.
Pharmacokinetic analysis and pharmacodynamic evidence of autophagy inhibition in patients with newly diagnosed glioblastoma treated on a phase I trial of hydroxychloroquine in combination with adjuvant temozolomide and radiation (ABTC 0603). (2010)

3086 Background: Preclinical studies indicate autophagy inhibition by hydroxychloroquine (HCQ) can augment the efficacy of DNA damaging cancer therapy. The primary objective of this trial was to determine the maximum tolerated dose (MTD) of HCQ in combination with adjuvant chemoradiation and temozolomide (TMZ) for glioblastoma (GBM). Methods: A 3+3 phase I trial design was conducted in surgically resected GBM patients (Pts). Pts received HCQ (200 -800 mg po qd) with radiation therapy (RT) and concurrent TMZ (75 mg/m2 po qd) followed by adjuvant TMZ (150-200 mg/m2 po qd ) 5/28 days for up to 6 cycles. Limited pharmacokinetic (PK) sampling and a novel high performance liquid chromatography/tandem mass spectroscopy assay for HCQ and metabolites were used to build a population PK model and blood concentration relationships. Quantitative electron microscopy (EM) and immunoblotting against the autophagy marker LC3 were used to assess therapy-associated changes in autophagic vesicles (AV) in peripheral blood mononuclear cells (PBMC). Results: 17 patients were enrolled at 6 centers with 15 pts evaluable for dose limiting toxicities (DLT). No DLT was observed in cohorts 1 or 2 (200, 400 mg HCQ). In cohort 3 (800 mg HCQ) 3/3 pts experienced Grade 3-4 neutropenia and thrombocytopenia, one with fever and sepsis. Deescalation of HCQ to 400 mg and 600 mg qd resulted in no DLTs and HCQ 600 mg qd was found to be the MTD. PK analysis indicated dose-proportional exposure for HCQ. Concentrations of HCQ which preclinical studies indicate are required for autophagy inhibition were achieved. Significant therapy-associated increases in AV with confirmatory elevations in LC3II were observed in PBMC in 1/5 pts at 400 mg, 2/3 patients at 600 mg and 2/2 patients at 800 mg HCQ. Conclusions: HCQ 600 mg is the MTD in this regimen and population. Dose-dependent myelosuppresion suggests a mechanistic interaction between HCQ and TMZ/RT. A novel PD assay for autophagy inhibition detected HCQ dose-dependent changes in AV in PBMC. Analyses of PK-PD interactions and a phase II study are underway. No significant financial relationships to disclose.
让我好好地“锁”住你 (2004)

作为一名电脑用户，肯定会常遇到一些“麻烦”的事，像在办公室的电脑被同事偷看隐私，或被Boss发现干私活：放在寝审的电脑未经允许，便被他人使用……这没有安全感的日子谁都会觉得难受。“吃一堑．长一智”，如能未雨绸缪，把电脑给“锁”上，烦恼皆休岂不更好，
Fine mapping of transcripts expressed from the US6 gene family of human cytomegalovirus strain AD169 (1991)

By sequence analysis (K. Weston and B. G. Barrell, J. Mol. Biol. 192:177-208, 1986), the human cytomegalovirus (HCMV) strain AD169 HindIII X DNA fragment contains six open reading frames (US6 through US11; called the US6 family) which may encode glycoproteins. Sense transcripts from the US6 family were mapped. The kinetics of appearance of steady-state cytoplasmic RNA was different for each transcription unit. The 1.5-kb US11-US10 and the 1.7-kb US9-US8 transcripts belonged to the early kinetic class. The former reached peak abundance by 8 h postinfection, while the latter peaked at 24 h postinfection. These RNAs greatly decreased in abundance by 48 to 72 h after infection, unlike transcripts from other HCMV early transcription units reported previously. US6 and US7 messages were most abundant at late times postinfection. US6 transcripts utilized different initiation sites at early or late times postinfection. There was evidence for both spliced and unspliced messages from this family. In a transient expression assay, chimeric plasmids containing the regions upstream of the mapped transcription initiation sites were active in promoting indicator gene expression in HCMV-infected, but not uninfected, human foreskin fibroblast cells.