gebhart/patrepeval huggingface dataset:
Combinatorial Pure Exploration of Multi-Armed Bandits (2014)

We study the combinatorial pure exploration (CPE) problem in the stochastic multi-armed bandit setting, where a learner explores a set of arms with the objective of identifying the optimal member of a decision class, which is a collection of subsets of arms with certain combinatorial structures such as size-K subsets, matchings, spanning trees or paths, etc. The CPE problem represents a rich class of pure exploration tasks which covers not only many existing models but also novel cases where the object of interest has a non-trivial combinatorial structure. In this paper, we provide a series of results for the general CPE problem. We present general learning algorithms which work for all decision classes that admit offline maximization oracles in both fixed confidence and fixed budget settings. We prove problem-dependent upper bounds of our algorithms. Our analysis exploits the combinatorial structures of the decision classes and introduces a new analytic tool. We also establish a general problem-dependent lower bound for the CPE problem. Our results show that the proposed algorithms achieve the optimal sample complexity (within logarithmic factors) for many decision classes. In addition, applying our results back to the problems of top-K arms identification and multiple bandit best arms identification, we recover the best available upper bounds up to constant factors and partially resolve a conjecture on the lower bounds. 1
Label-Free Optical Detection of Biomolecular Translocation through Nanopore Arrays (2014)

In recent years, nanopores have emerged as exceptionally promising single-molecule sensors due to their ability to detect biomolecules at subfemtomole levels in a label-free manner. Development of a high-throughput nanopore-based biosensor requires multiplexing of nanopore measurements. Electrical detection, however, poses a challenge, as each nanopore circuit must be electrically independent, which requires complex nanofluidics and embedded electrodes. Here, we present an optical method for simultaneous measurements of the ionic current across an array of solid-state nanopores, requiring no additional fabrication steps. Proof-of-principle experiments are conducted that show simultaneous optical detection and characterization of ssDNA and dsDNA using an array of pores. Through a comparison with electrical measurements, we show that optical measurements are capable of accessing equivalent transmembrane current information.
Review of the damped least-squares inverse kinematics with experiments on an industrial robot manipulator (1994)

The goal of this paper is to present experimental results on the implementation of the damped least-squares method for the six-joint ABB IRb2000 industrial robot manipulator. A number of inverse kinematics schemes are reviewed which allow robot control through kinematic singularities. The basic scheme adopts a damped least-squares inverse of the manipulator Jacobian with a varying damping factor acting in the neighborhood of singularities. The effect of a weighted damped least-squares solution is investigated to provide user-defined accuracy capabilities along prescribed end-effector space directions. An online estimation algorithm is employed to measure closeness to singular configurations. A feedback correction error term is introduced to ensure algorithm tracking convergence and its effect on the joint velocity solution is discussed. Computational aspects are discussed in view of real-time implementation of the proposed schemes. Experimental case studies are developed to investigate manipulator performance in the case of critical end-effector trajectories passing through and near the shoulder and wrist singularities of the structure.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Small-molecule TrkB receptor agonists improve motor function and extend survival in a mouse model of Huntington's disease (2013)

Huntington's disease (HD) is a fatal neurodegenerative disease characterized by abnormal motor coordination, cognitive decline and psychiatric disorders. This disease is caused by an expanded CAG trinucleotide repeat in the gene encoding the protein huntingtin. Reduced levels of brain-derived neurotrophic factor (BDNF) in the brain, which results from transcriptional inhibition and axonal transport deficits mediated by mutant huntingtin, have been suggested as critical factors underlying selective neurodegeneration in both HD patients and HD mouse models. BDNF activates its high-affinity receptor TrkB and promotes neuronal survival; restoring BDNF signaling is thus of particular therapeutic interest. In the present study, we evaluated the ability of a small-molecule TrkB agonist 7,8-dihydroxyflavone (7,8-DHF) and its synthetic derivative 4'-dimethylamino-7,8- dihydroxyflavone (4'-DMA-7,8-DHF) to protect neurons in the well-characterized N171-82Q HD mouse model. We found that chronic administration of 7, 8-DHF (5 mg/kg) or 4'-DMA-7,8-DHF (1 mg/kg) significantly improved motor deficits, ameliorated brain atrophy and extended survival in these N171-82Q HD mice. Moreover, 4'-DMA-7,8-DHF preserved DARPP32 levels in the striatum and rescued mutant huntingtin-induced impairment of neurogenesis in the N171-82Q HD mice. These data highlight consideration of TrkB as a therapeutic target in HD and suggest that small-molecule TrkB agonists that penetrate the brain have high potential to be further tested in clinical trials of HD.
Electroless copper deposition for ULSI (1995)

This work reviews the electroless copper deposition process as a metallization method for integrated circuit applications. We review the solution chemistry and reaction thermodynamics as well as the deposition kinetics for deposition on flat surfaces and on patterned surfaces with minimum dimensions between 0.1 and 1.0μm. The development of an alkali-free solution for sodium-free copper deposition is presented and the optimization of this solution for minimum as-deposited film resistivity is described. The integration of electroless technology in integrated circuit production is discussed and two basic approaches are presented, planar and non-planar. Finally, process flows for several integration methods are summarized and discussed.
Requirement for GroEL/GroES-Dependent Protein Folding under Nonpermissive Conditions of Macromolecular Crowding (2002)

Macromolecular crowding is a critical parameter affecting the efficiency of cellular protein folding. Here we show that the proteins dihydrofolate reductase, enolase, and green fluorescent protein, which can fold spontaneously in diluted buffer, lose this ability in a crowded environment. Instead, they accumulate as soluble, protease-sensitive non-native species. Their folding becomes dependent on the complete GroEL/GroES chaperonin system and is not affected by trap-GroEL, indicating that folding has to occur in the chaperonin cavity with release of nativelike proteins into the bulk solution. In addition, we demonstrate that efficient folding in the chaperonin cavity requires ATP hydrolysis, as formation of ternary GroEL/GroES complexes with substrate proteins in the presence of ADP results only in very inefficient reactivation. However, protein refolding reactions using ADP-fluoroaluminate complexes, or single-ring GroEL and GroES under conditions where only a single round of ATP hydrolysis occurs, yield large amounts of refolded enzymes. Thus, the mode of initial ternary complex formation appears to be critical for subsequent productive release of substrate into the cavity under certain crowding conditions, and is only efficient when triggered by ATP hydrolysis. Our data indicate that stringent conditions of crowding can impart a stronger dependence of folding proteins on the assistance by chaperonins.
A sequential enriched design for target patient population in psychiatric clinical trials (2014)

High placebo response is widely believed to be one major reason why many psychiatric clinical trials fail to demonstrate drug efficacy. In order to alleviate this problem, research has developed several enrichment designs, including the parallel design with a placebo lead-in phase, the sequential parallel design, and a recently proposed two-way enriched design. While these designs have been evaluated and discussed individually, their effectiveness against each other has not been rigorously compared. The current study examines the various enrichment designs simultaneously. Building on their strengths, we introduce a new improved design named' sequential enriched design' (SED) aimed at removing not only patients with high placebo response but also patients who do not respond to any treatment from the study. The SED begins with a double-blind placebo lead-in phase followed by a traditional parallel design in the first stage. Only patients who respond to the drug in the first stage are re-randomized to the drug or placebo at the second stage. We simulate data for a mixed population composed of four subgroups of patients who are predetermined as to whether they respond to drug or not as well as to placebo or not. By focusing on the target patients whose responses reflect the drug's efficacy,we evaluate the bias, mean squared error, and power for different designs. We demonstrate that the SED produces a less biased estimate for the target treatment effect and yields reasonably high power in general compared with the other designs.
Reactions with Pyridine-2-Thiones: A New Route for the Synthesis of Several New Pyridines and Fused Azolo- and Azinopyridines (2001)

Abstract The synthetic potential of our newly synthesized 3-cyano-pyridinethione derivatives (la,b) was further demonstrated via their use to synthesize each of 2-S-ethoxycarbonylmethylpyridines (3a,b), thieno[2,3-b] pyridines (4a,b); (7a,b), pyrido[3′2′4,5]thieno[3,2-clpyridazines (8a,b), 2-methylthiopyridines (9a,b), 2-hydrazinopyridines (lOa,b), 3-aminopyrazolo[3,4-b]pyridines (lla,b), pyrazolo[3,4-blpyridin-3-ylphenylthioureas (12a,b), and 3-diazotized aminopyrazolo[3,4-b]pyridine (13a,b) derivatives via their reactions with the corresponding reagents. Structures of the newly synthesized heterocyclic derivatives were established on the basis of elemental analyses and spectral data studies.
Real-Time Speech Coding (1982)

This paper reviews our recent efforts in the design and implementation of real-time speech coders. We discuss our approach and methodology for real-time hardware for coder techniques ranging from low to high complexity. Examples of realizations are given for each approach. They include adaptive differential PCM coding, subband coding, harmonic scaling with subband coding, and adaptive transform coding. Low to medium complexity techniques are based on the use of the Bell Laboratories digital signal processing (DSP) integrated circuit. High complexity block processing techniques are based on the use of an array processing computer. We conclude with an assessment of the performance versus complexity tradeoffs involved in these coding methods.
A comprehensive ChIP–chip analysis of E2F1, E2F4, and E2F6 in normal and tumor cells reveals interchangeable roles of E2F family members (2007)

Using ChIP–chip assays (employing ENCODE arrays and core promoter arrays), we examined the binding patterns of three members of the E2F family in five cell types. We determined that most E2F1, E2F4, and E2F6 binding sites are located within 2 kb of a transcription start site, in both normal and tumor cells. In fact, the majority of promoters that are active (as defined by TAF1 or POLR2A binding) in GM06990 B lymphocytes and Ntera2 carcinoma cells were also bound by an E2F. This very close relationship between E2F binding sites and binding sites for general transcription factors in both normal and tumor cells suggests that a chromatin-bound E2F may be a signpost for active transcription initiation complexes. In general, we found that several E2Fs bind to a given promoter and that there is only modest cell type specificity of the E2F family. Thus, it is difficult to assess the role of any particular E2F in transcriptional regulation, due to extreme redundancy of target promoters. However, Ntera2 carcinoma cells were exceptional in that a large set of promoters were bound by E2F6, but not by E2F1 or E2F4. It has been proposed that E2F6 contributes to gene silencing by recruiting enzymes involved in methylating histone H3. To test this hypothesis, we created Ntera2 cell lines harboring shRNAs to E2F6. We found that reduction of E2F6 only induced minimal alteration of the transcriptome of Ntera2 transcriptome. Our results support the concept of functional redundancy in the E2F family and suggest that E2F6 is not critical for histone methylation.
Localization of a putative transcriptional regulator (ATRX) at pericentromeric heterochromatin and the short arms of acrocentric chromosomes (1999)

ATRX is a member of the SNF2 family of helicase/ATPases that is thought to regulate gene expression via an effect on chromatin structure and/or function. Mutations in the hATRX gene cause severe syndromal mental retardation associated with alpha-thalassemia. Using indirect immunofluorescence and confocal microscopy we have shown that ATRX protein is associated with pericentromeric heterochromatin during interphase and mitosis. By coimmunofluorescence, ATRX localizes with a mouse homologue of the Drosophila heterochromatic protein HP1 in vivo, consistent with a previous two-hybrid screen identifying this interaction. From the analysis of a trap assay for nuclear proteins, we have shown that the localization of ATRX to heterochromatin is encoded by its N-terminal region, which contains a conserved plant homeodomain-like finger and a coiled-coil domain. In addition to its association with heterochromatin, at metaphase ATRX clearly binds to the short arms of human acrocentric chromosomes, where the arrays of ribosomal DNA are located. The unexpected association of a putative transcriptional regulator with highly repetitive DNA provides a potential explanation for the variability in phenotype of patients with identical mutations in the ATRX gene.
The use of three‐dimensional collagen gels for the study of tumour cell invasion in vitro: Experimental parameters influencing cell migration into the gel matrix (1982)

We have been using three-dimensional gels of native collagen fibres as a substratum for the study of cell migratory behaviour. The objective of this work has been to develop an experimental model system for the study of tumour cell invasion. Data are presented in this communication concerning the effects of a number of experimental parameters on the migration of human foreskin fibroblasts (normal) and a Syrian hamster melanoma cell line (tumour) into three-dimensional gels of native collagen fibres. We find that the migration of both these cell types into the gel matrix is affected by the concentration of collagen in the gel, as well as by the initial density of cells plated onto the gel and the density of cells in the stock culture dishes. These results are discussed in terms of the control of cell migration into the gel and also demonstrate the potential utility of this model system for the study of tumour cell invasion.
Stable molecular transformation of Toxoplasma gondii: a selectable dihydrofolate reductase-thymidylate synthase marker based on drug-resistance mutations in malaria. (1993)

To facilitate genetic analysis of the protozoan parasite Toxoplasma gondii, sequences derived from the parasite's fused dihydrofolate reductase-thymidylate synthase (DHFR-TS) gene have been used to produce vectors suitable for stable molecular transformation. Mutations introduced into the DHFR coding region by analogy with pyrimethamine-resistant malaria confer drug resistance to Toxoplasma, providing useful information on the structure of fused DHFR-TS enzymes and a powerful selectable marker for molecular genetic studies. Depending on the particular drug-resistance allele employed and the conditions of selection, stable resistance can be generated either by single copy nonhomologous insertion into chromosomal DNA or by massively amplified transgenes. Frequencies of integration are independent of selection, and transgenes are stable without continued selection. Cointegration of a reporter gene adjacent to the selectable marker (under the control of an independent promoter) shows no loss of the cointegrated sequences over many parasite generations. By bringing the full power of molecular genetic analysis to bear on Toxoplasma, these studies should greatly facilitate the development of a model genetic system for Apicomplexan parasites.
Nucleotide sequence of v-rel: the oncogene of reticuloendotheliosis virus. (1983)

The nucleotide sequence of v-rel, the oncogene carried by reticuloendotheliosis virus (REV), has been determined. The defective transforming genome REV arose through the insertion of v-rel (1,415 nucleotides) into the env gene of the helper virus REV-A. The predicted rel protein (503 amino acids) employs the REV-A env initiator and terminates within the p20E region of env. Because there are no natural antisera that detect the REV transforming protein, this nucleotide sequence provides the first step toward its isolation and characterization. The predicted protein is clearly distinct from all other reported transforming proteins but may be very distantly related to members of the src family.
Direct Analysis of Viral-Specific CD8+ T Cells with Soluble HLA-A2/Tax11-19 Tetramer Complexes in Patients with Human T Cell Lymphotropic Virus-Associated Myelopathy (1999)

Human T cell lymphotropic virus-I (HTLV-I)-associated myelopathy is a slowly progressive neurologic disease characterized by inflammatory infiltrates in the central nervous system accompanied by clonal expansion of HTLV-I-reactive CD8+ T-cells. In patients carrying the HLA-A2 allele, the immune response is primarily directed to the Tax11-19 peptide. The frequency, activation state, and TCR usage of HLA-A2/Tax11-19 binding T cells in patients with HTLV-I-associated myelopathy was determined using MHC class I tetramers loaded with the Tax11-19 peptide. Circulating Tax11-19-reactive T cells were found at very high frequencies, approaching 1:10 circulating CD8+ T cells. T cells binding HLA-A2/Tax11-19 consisted of heterogeneous populations expressing different chemokine receptors and the IL-2R beta-chain but not the IL-2R alpha-chain. Additionally, Tax11-19-reactive CD8+ T cells used one predominant TCR Vbeta-chain for the recognition of the HLA-A2/Tax11-19 complex. These data provide direct evidence for high frequencies of circulating Tax11-19-reactive CD8+ T cells in patients with HTLV-I-associated myelopathy.
Microenvironmental regulation of the sinusoidal endothelial cell phenotype in vitro # (2009)

Collectively, this study has identified several microenvironmental regulators of liver sinusoidal endothelial cells that prolong their phenotypic functions for up to 2 weeks in culture, enabling the development of better in vitro models of liver physiology and disease.
Lower Limb Human Muscle Enhancer (2001)

Abstract This paper describes the design, control, and testing of a Human Muscle Enhancer (HME) system that will augment the muscle capabilities of subjects requiring partial lower-limb weight-bearing gait support. The HME described in this paper is a pneumatically actuated quick connecting exoskeleton system that attaches to the foot and hip area of the body, thus “closing” the lower body kinematic chain. Control of the system is achieved by using encoders at the knee joints and Myo-Pneumatic (MP) Sensors implanted into the shoes and outer garments of the human. To test this design concept, a lower body exoskeleton test fixture has been fabricated. The test fixture mimics the human leg with the top cylinder providing the body weight on the leg. Another cylinder acts as leg muscles to provide the adjustable human reaction of the leg. Preliminary open and closed loop control tests have been performed that demonstate the capability of controlling the HME using the MP sensors.
5-HT3 Receptors (2004)

5-HT(3)-receptor antagonists are highly selective competitive inhibitors of the 5-HT(3)-receptor with negligible affinity for other receptors. They are potent, rapidly absorbed and easily penetrate the blood-brain barrier; metabolized by the cytochrome P450-system with half-life varying from 3-10 hours. The compounds investigated so far do not modify normal behaviour in animals or man and are well tolerated over wide dose ranges, the most common side effects being headache or constipation. Clinical efficacy was first established in chemotherapy-induced emesis (and then in radiotherapy-induced and post-operative emesis), where 5-HT(3)-receptor antagonists set a new standard of antiemetic efficacy and tolerability. The 5-HT(3) receptor antagonists, via a central and / or peripheral action, have been shown to reduce secretion and motility in the gut and possess clinical utility in irritable bowel syndrome, and possibly other visceral pain disorders. Their value in fibromyalgia is being evaluated. In preclinical behavioural assays they induce effects consistent with anxiolysis, improved cognition, anti-dopaminergic activity and use in drug abuse and withdrawal. There is some evidence that ondansetron may reduce alcohol consumption in moderate alcohol abusers but overall, 5-HT(3) receptor antagonists seem to be of limited use in psychiatric disorders: where effects have been seen, they seem to be unusually sensitive to dose and stage of disease. Nevertheless, their antiemetic potential has been of great benefit to cancer patients and the possible extension of their use to bowel disorders may yet fulfil their initial exciting promise.
A high performance fine-grained approach to SRAM based FPGAs (2002)

This paper discusses the advantages of a reprogrammable partitioned "fine-grained" core-cell approach to FPGAs coupled with timing driven automated place and route software. Singh et al. (1992) have attempted to show that a medium to coarse cell structure and a fixed look-up table structure, is optimal for performance. Their findings were based primarily on empirical data. This paper demonstrates, that a fine grained structure, with hierarchical routing resources can achieve results which are equal to or better than the established architectures.
CVD of SiO2 and related materials: An overview (1996)

An overview is presented of the chemical vapour deposition (CVD) of SiO2 and related materials, together with a description of their application in metal-oxide-semiconductor (MOS) devices, including device isolation, gate insulation passivation and planarisation. A comparison of CVD methods and precursors is presented for SiO2 as well as doped glasses, e.g. borosilicate glasses (BSG), phosphosilicate glasses (PSG), borophosphosilicate glasses (BPSG), and arsenosilicates glasses (AsSG).