gebhart/patrepeval huggingface dataset:
WaveNet: A Generative Model for Raw Audio (2016)

This paper introduces WaveNet, a deep neural network for generating raw audio waveforms. The model is fully probabilistic and autoregressive, with the predictive distribution for each audio sample conditioned on all previous ones; nonetheless we show that it can be efficiently trained on data with tens of thousands of samples per second of audio. When applied to text-to-speech, it yields state-of-the-art performance, with human listeners rating it as significantly more natural sounding than the best parametric and concatenative systems for both English and Mandarin. A single WaveNet can capture the characteristics of many different speakers with equal fidelity, and can switch between them by conditioning on the speaker identity. When trained to model music, we find that it generates novel and often highly realistic musical fragments. We also show that it can be employed as a discriminative model, returning promising results for phoneme recognition.
Identification of the glycogenic compound 5-iodotubercidin as a general protein kinase inhibitor (1994)

Addition of micromolar concentrations of the adenosine derivative 5-iodotubercidin (Itu) initiates glycogen synthesis in isolated hepatocytes by causing inactivation of phosphorylase and activation of glycogen synthase [Flückiger-Isler and Walter (1993) Biochem. J. 292, 85-91]. We report here that Itu also antagonizes the effects of saturating concentrations of glucagon and vasopressin on these enzymes. The Itu-induced activation of glycogen synthase could not be explained by the removal of phosphorylase a (a potent inhibitor of the glycogen-associated synthase phosphatase). When tested on purified enzymes, Itu did not affect the activities of the major Ser/Thr-specific protein phosphatases (PP-1, PP-2A, PP-2B and PP-2C), but it inhibited various Ser/Thr-specific protein kinases as well as the tyrosine kinase activity of the insulin receptor (IC50 between 0.4 and 28 microM at 10-15 microM ATP). Tubercidin, which did not affect glycogen synthase or phosphorylase in liver cells, was 300 times less potent as a protein kinase inhibitor. Kinetic analysis of the inhibition of casein kinase-1 and protein kinase A showed that Itu acts as a competitive inhibitor with respect to ATP, and as a mixed-type inhibitor with respect to the protein substrate. We propose that Itu inactivates phosphorylase and activates glycogen synthase by inhibiting phosphorylase kinase and various glycogen synthase kinases. Consistent with the broad specificity of Itu in vitro, this compound decreased the phosphorylation level of numerous phosphopolypeptides in intact liver cells. Our data suggest that at least some of the biological effects of Itu can be explained by an inhibition of protein kinases.
Rearrangement of 3-(N-Heteroarylamino)-1,2,5-oxadiazoles: Triazolo[1,5-a]quinolines and Triazolo[1,5-a]pyridines (1993)

The rearrangement reaction of 1,2,5-oxadiazole derivatives bearing quinoline and pyridine heterocycles in a N-C-N side chain sequence was investigated. Triazolo[1,5-a]quinoline and triazolo[1,5-a]pyridine oximes were obtained in good yield
Synthesis of C-ribosyl 1,2,4-triazolo[3,4-f  ][1,2,4]triazines as inhibitors of adenosine and AMP deaminases (1999)

Modified C-nucleosides and nucleotides with an enhanced tendency to undergo covalent hydration are of interest as potential inhibitors of adenosine deaminase (ADA) and AMP deaminase, respectively. In a search for such compounds we have synthesized 6-dimethylamino-3-(β-D-ribofuranosyl)-1,2,4-triazolo[3,4-f][1,2,4]triazine 4 in four steps (42% overall yield) from the readily available allonic acid 6 and the hydrazine 7. The hydrazide 16 derived from 6 and 7 (78%) is converted directly into the cyclised chloro compound 19 (62%) with phosphorus trichloride oxide, followed by dechlorination (96%) and deprotection (90%). Riboside 4 undergoes partial hydration in water to the covalent hydrate 22, and is a modest inhibitor of mammalian ADA (IC50 180 µM).
Attachment of Gold Nanograins onto Colloidal Magnetite Nanocrystals (2005)

The successful attachment of 2−3 nm gold particles to ∼10 nm Fe3O4 nanocrystals through a simple, two-step chemically controlled procedure is reported. The surface of individual, relatively monodisperse, Fe3O4 nanospheres forming a stable colloidal methanolic solution is coated with an amino-terminated silane, peptized to induce positive charges on the particles' surfaces and then treated with a colloidal solution of negatively charged Au nanoparticles. A detailed investigation by transmission electron microscopy, X-ray diffraction, UV−vis, inductively coupled plasma, and superconducting quantum interference device magnetometry was performed in order to elucidate the morphology and properties of the nanocomposites. Due to their low concentration and small size of the attached Au particles, the optical properties are not observable in the case of the Fe3O4/Au nanocomposites. Additionally, the colloidal Fe3O4/Au nanocomposites are highly stable against separation and exhibit magnetic properties similar to those of the parent Fe3O4 nanocrystals. These novel nanoarchitectures open up new opportunities for the use of magnetite nanoparticles for in-vivo biomedical applications through chemical bonding of bioactive molecules to the attached Au nanoparticles.
Gene expression profiling in follicular lymphoma to assess clinical aggressiveness and to guide the choice of treatment (2004)

Follicular lymphoma (FL) is a disease characterized by a long clinical course marked by frequent relapses that vary in clinical aggressiveness over time. Therefore, the main dilemma at each relapse is the choice for the most effective treatment for optimal disease control and failure-free survival while at the same time avoiding overtreatment and harmful side effects. The selection for more aggressive treatment is currently based on histologic grading and clinical criteria; however, in up to 30% of all cases these methods prove to be insufficient. Using supervised classification on a training set of paired samples from patients who experienced either an indolent or aggressive disease course, a gene expression profile of 81 genes was established that could, with an accuracy of 100%, distinguish low-grade from high-grade disease. This profile accurately classified 93% of the FL samples in an independent validation set. Most important, in a third series of FL cases where histologic grading was ambiguous, precluding meaningful morphologic guidance, the 81-gene profile shows a classification accuracy of 94%. The FL stratification profile is a more reliable marker of clinical behavior than the currently used histologic grading and clinical criteria and may provide an important alternative to guide the choice of therapy in patients with FL both at presentation and at relapse.
Heregulin Induces Phosphorylation of BRCA1 through Phosphatidylinositol 3-Kinase/AKT in Breast Cancer Cells (1999)

The breast cancer susceptibility gene BRCA1 encodes a nuclear phosphoprotein that acts as a tumor suppressor. Phosphorylation of BRCA1 has been implicated in altering its function, however, the pathway(s) that leads to the phosphorylation of BRCA1 has not been described. Here, a signaling pathway by which heregulin induces cell cycle-independent phosphorylation of BRCA1 was delineated. We showed that heregulin stimulation induced the phosphorylation of BRCA1 and concomitant activation of the serine/threonine kinase AKT in T47D human breast cancer cells. Heregulin-induced phosphorylation of BRCA1 was abrogated by phosphatidylinositol 3-kinase (PI3K) inhibitors and by a dominant-negative AKT. In the absence of heregulin, the ectopic expression of the constitutively active p110 subunit of PI3K was sufficient to induce BRCA1 phosphorylation. Furthermore, the purified glutathione S-transferase/AKT kinase phosphorylated BRCA1 in vitro. We have also shown that the phosphorylation of BRCA1 by AKT occurs on the residue Thr-509, which is located in the nuclear localization signal. These results reveal a novel signaling pathway that links extracellular signals to the phosphorylation of BRCA1 in breast cancer cells.
PVFS : a parallel file system for linux clusters (2000)

As Linux clusters have matured as platforms for low-cost, high-performance parallel computing, software packages to provide many key services have emerged, especially in areas such as message passing and networking. One area devoid of support, however, has been parallel file systems, which are critical for high-performance I/O on such clusters. We have developed a parallel file system for Linux clusters, called the Parallel Virtual File System (PVFS). PVFS is intended both as a high-performance parallel file system that anyone can download and use and as a tool for pursuing further research in parallel I/O and parallel file systems for Linux clusters. In this paper, we describe the design and implementation of PVFS and present performance results on the Chiba City cluster at Argonne. We provide performance results for a workload of concurrent reads and writes for various numbers of compute nodes, I/O nodes, and I/O request sizes. We also present performance results for MPI-IO on PVFS, both for a concurrent read/write workload and for the BTIO benchmark. We compare the I/O performance when using a Myrinet network versus a fast-ethernet network for I/O-related communication in PVFS. We obtained read and write bandwidths as high as 700 Mbytes/sec with Myrinet and 225 Mbytes/sec with fast ethernet.
Computational design of linkage-based characters (2014)

We present a design system for linkage-based characters, combining form and function in an aesthetically-pleasing manner. Linkage-based character design exhibits a mix of discrete and continuous problems, making for a highly unintuitive design space that is difficult to navigate without assistance. Our system significantly simplifies this task by allowing users to interactively browse different topology options, thus guiding the discrete set of choices that need to be made. A subsequent continuous optimization step improves motion quality and, crucially, safeguards against singularities. We demonstrate the flexibility of our method on a diverse set of character designs, and then realize our designs by physically fabricating prototypes.
Automated cycle sequencing with Taquenase: protocols for internal labeling, dye primer and "doublex" simultaneous sequencing. (1997)

This paper describes automated cycle sequencing protocols for internal labeling, dye primer and "doublex" simultaneous sequencing using Taquenase, a new genetically modified DNA polymerase with increased thermostability. Sequencing performance both with labeled and unlabeled primer yields uniform unambiguous signals up to the resolution limit of the sequencing gels. Primer walking with internal labeling was successfully performed on Pl-derived artificial chromosome (PAC) constructs with 130-kb inserts. Taquenase, a commercially available modified thermostable sequencing enzyme (delta 280, F667Y Taq DNA polymerase), incorporates a variety of fluorescent dNTPs carrying fluorescein isothiocyanate, TexasRed or Cy5 labels during the cycle-sequencing process with higher efficiency than other thermostable DNA polymerases. Comparison to other modified Taq DNA polymerases suggests that the particular N-terminal deletion of Taquenase rather than the presence of the F667Y mutation is responsible for the efficient incorporation and extension of labeled dNTPs. Taquenase makes feasible highly accurate "doublex" simultaneous cylce sequencing on both strands of template DNA with two internal labels or two dye-labeled primers in combination with the EMBL-2-dye DNA sequencing system, ARAKIS, or with two commercial DNA sequencers. It allows up to 2000 bases at > 99% accuracy to be determined in a single reaction.
New cellular schemes for spectral efficiency (1987)

Assuming the constraint of an allocated frequency spectrum, two new schemes are suggested to increase spectral efficiency. Furthermore, the two new schemes can be integrated to become a hybrid system and offer greater performance which takes advantage of the merits and performance of each individual scheme.
Disruption of p53 function sensitizes breast cancer MCF-7 cells to cisplatin and pentoxifylline. (1995)

The possibility that appropriately designed chemotherapy could act selectively against p53-defective tumor cells was explored in MCF-7 human breast cancer cells. These cells were chosen because they have normal p53 function but are representative of a tumor cell type that does not readily undergo p53-dependent apoptosis. Two sublines (MCF-7/E6 and MCF-7/mu-p53) were established in which p53 function was disrupted by transfection with either the human papillomavirus type-16 E6 gene or a dominant-negative mutant p53 gene. p53 function in MCF-7/E6 and MCF-7/mu-p53 cells was defective relative to control cells in that there were no increases in p53 or p21Waf1/Cip1 protein levels and no G1 arrest following exposure to ionizing radiation. Survival assays showed that p53 disruption sensitized MCF-7 cells to cisplatin (CDDP) but not to several other DNA-damaging agents. CDDP sensitization was not limited to MCF-7 cells since p53 disruption in human colon carcinoma RKO cells also enhanced sensitivity to CDDP. Contrary to the other DNA-damaging agents tested, CDDP-induced DNA lesions are repaired extensively by nucleotide excision, and in agreement with a defect in this process, MCF-7/E6 and MCF-7/mu-p53 cells exhibited a reduced ability to repair a CDDP-damaged chloramphenicol acetyltransferase-reporter plasmid transfected into the cells. Therefore, we attributed the increased CDDP sensitivity of MCF-7 cells with disrupted p53 to defects in G1 checkpoint control, nucleotide excision repair, or both. The G2 checkpoint inhibitor pentoxifylline exhibited synergism with CDDP in killing MCF-7/E6 cells but did not affect sensitivity of the control cells. Moreover, pentoxifylline inhibited G2 checkpoint function to a greater extent in MCF-7/E6 than in the parental cells. These results suggested that, in the absence of p53 function, cancer cells are more vulnerable to G2 checkpoint abrogators. Our results show that a combination of CDDP and pentoxifylline is capable of synergistic and preferential killing of p53-defective tumor cells that do not readily undergo apoptosis.
Determination of a 17484 bp nucleotide sequence around the 39 region of the Bacillus subtilis chromosome and similarity analysis of the products of putative ORFs (1995)

We have determined a 17,484 bp nucleotide sequence around the 39 degrees region, located about 480 kb downstream from the zero position of the Bacillus subtilis chromosome physical map. Among the 17 putative ORFs identified, orf1 and orf2 seem to correspond to mtlA and mtlB, encoding mannitol-specific phosphotransferase enzyme II and mannitol-1-phosphate dehydrogenase, respectively. orf4 seems to be another signal peptidase I gene (sipS) of B. subtilis. The putative products of six ORFs were similar to known proteins in data banks, namely a hypothetical 29.7 kDa protein of Escherichia coli (Orf7), a lactam utilization protein (Orf8), the urea amidolyase of yeast (Orf12), the IcIR regulatory protein for aceAB of Salmonella typhimurium (Orf13), penicillin-binding protein 2 (Orf16) and aryl-alcohol dehydrogenase (Orf17). The amino acid sequence of Orf3 showed 34% identity with that of LeuC of B. subtilis, though they seem to be functionally different. The remaining seven ORFs did not show similarity to any known proteins.
Recombinant human iduronate-2-sulphatase: correction of mucopolysaccharidosis-type II fibroblasts and characterization of the purified enzyme (1993)

Mucopolysaccharidosis type II (MPS II, Hunter syndrome) is an X-chromosome-linked recessive lysosomal storage disorder that results from a deficiency of iduronate-2-sulphatase (12S). Patients with MPS II store and excrete large amounts of partially degraded heparan sulphate and dermatan sulphate. In order to evaluate enzyme-replacement therapy for MPS II we have expressed a chimaeric I2S cDNA in CHO (Chinese-hamster ovary)-K1 cells utilizing a plasmid vector that places the cDNA under the transcriptional control of the human polypeptide-chain-elongation factor-1 alpha gene promoter. A clonal cell line that accumulated recombinant I2S at greater than 10 mg/ml in conditioned medium was identified. Enzyme secreted from this cell line grown in the presence of NH4Cl was shown to be endocytosed into MPS II fibroblasts via the mannose 6-phosphate receptor and localized to the lysosomal compartment, resulting in correction of the storage phenotype of these cells. Milligram quantities of the recombinant I2S were purified, and the enzyme was shown to have a pH optimum and kinetic parameters similar to those for the mature form of I2S purified from human liver. The recombinant I2S had a molecular mass of approx. 90 kDa; this was reduced to 60 kDa by endoglycosidase treatment.
Change in Brain Magnetic Resonance Spectroscopy after Treatment during Acute HIV Infection (2012)

We detected cellular inflammation in the absence of measurable neuronal injury within the first month of HIV infection, and normalization of this inflammation following acutely administered ART. Our findings suggest that early ART may be neuroprotective in HIV infection by mitigating processes leading to CNS injury.
Janus Droplets: Liquid Marbles Coated with Dielectric/Semiconductor Particles (2010)

The manufacturing of water droplets wrapped with two different powders, carbon black (semiconductor) and polytetrafluoroethylene (dielectric), is presented. Droplets composed of two hemispheres (Janus droplets) characterized by various physical and chemical properties are reported first. Watermelon-like striped liquid marbles are reported. Janus droplets remained stable on solid and liquid supports and could be activated with an electric field.
Role of fecal calprotectin as a biomarker of intestinal inflammation in inflammatory bowel disease (2006)

Calprotectin is an abundant neutrophil protein found in both plasma and stool that is markedly elevated in infectious and inflammatory conditions, including inflammatory bowel disease (IBD). We conducted a systematic review of the published literature regarding fecal calprotectin to evaluate its potential as a noninvasive marker of neutrophilic intestinal inflammation. Reference ranges for fecal calprotectin have been established in healthy adults and children, and elevated concentrations of fecal calprotectin have been demonstrated in numerous studies of patients with IBD. Fecal calprotectin correlates well with histological inflammation as detected by colonoscopy with biopsies and has been shown successfully to predict relapses and detect pouchitis in patients with IBD. Fecal calprotectin has been shown to consistently differentiate IBD from irritable bowel syndrome because it has excellent negative predictive value in ruling out IBD in undiagnosed, symptomatic patients. Fecal calprotectin also may be useful in determining whether clinical symptoms in patients with known IBD are caused by disease flares or noninflammatory complications/underlying irritable bowel syndrome and in providing objective evidence of response to treatment. Although more studies are needed to define fully the role of fecal calprotectin, convincing studies and growing clinical experience point to an expanded role in the diagnosis and management of IBD.
Phase I trial of valaciclovir, the L-valyl ester of acyclovir, in patients with advanced human immunodeficiency virus disease (1994)

Valaciclovir, the L-valyl ester of acyclovir, is rapidly and extensively converted in humans to acyclovir after oral administration by first-pass metabolism. A phase I study was conducted in two cohorts of volunteers with advanced human immunodeficiency virus (HIV) disease (absolute CD4 lymphocyte count of < 150 cells per microliters) who received oral valaciclovir at dosages of 1,000 or 2,000 mg four times daily for 30 days. All patients were clinically stable without any changes in underlying HIV-related medications for > or = 6 weeks prior to entry in study; these medications were continued throughout the study. Multiple-dose administration of valaciclovir showed a generally favorable safety profile. Nausea, vomiting, diarrhea, and abdominal pain each were reported in < or = 31% of the patients; of these symptoms, only one episode of diarrhea was considered causally related to valaciclovir exposure. Four patients developed neutropenia (two at each dose level) which was not clinically significant. There were no renal or neurologic adverse events. Valaciclovir was rapidly absorbed and converted to acyclovir, with plasma valaciclovir levels generally undetectable or levels of < or = 0.4 microgram/ml. After 3 h postdosing, valaciclovir was not detectable in plasma. Acyclovir was measurable in plasma as early as 15 min following valaciclovir dosing, and plasma concentrations of acyclovir greatly exceeded those of valaciclovir. The mean values for the maximum concentration of drug in plasma, time to maximum concentration of drug in plasma, area under the concentration-time curve from 0 h to infinity, and apparent half-life of acyclovir obtained after single- and multiple-dose valaciclovir administration in HIV-infected patients were similar to those reported in normal healthy volunteers. The time to maximum concentration in serum and half-life of acyclovir after valaciclovir administration were approximately 2 and 3 h, respectively, which were similar to those reported after oral administration of acyclovir itself. The mean trough and peak acyclovir concentrations and the daily area under the concentration-time curve acyclovir values at steady state were 2.5 and 8.4 micrograms/ml and 120 h micrograms/ml, respectively, after a dosage of 2,000 mg of valaciclovir four times daily. These values were approximately fivefold greater than those achieved with high dosages of oral acyclovir (800 mg, five times daily) and were not affected by continued use of medications necessary for management of advanced HIV disease. Thus, 2,000 mg of valaciclovir given orally four times daily should be evaluated for its potential efficacy in suppressing cytomegalovirus and other herpes group virus infections not optimally managed with current oral acyclovir therapy.
IL-23 Compensates for the Absence of IL-12p70 and Is Essential for the IL-17 Response during Tuberculosis but Is Dispensable for Protection and Antigen-Specific IFN-γ Responses if IL-12p70 Is Available (2005)

IL-12p70 induced IFN-gamma is required to control Mycobacterium tuberculosis growth; however, in the absence of IL-12p70, an IL-12p40-dependent pathway mediates induction of IFN-gamma and initial bacteriostatic activity. IL-23 is an IL-12p40-dependent cytokine containing an IL-12p40 subunit covalently bound to a p19 subunit that is implicated in the induction of CD4 T cells associated with autoimmunity and inflammation. We show that in IL-23 p19-deficient mice, mycobacterial growth is controlled, and there is no diminution in either the number of IFN-gamma-producing Ag-specific CD4 T cells or local IFN-gamma mRNA expression. Conversely, there is an almost total loss of both IL-17-producing Ag-specific CD4 T cells and local production of IL-17 mRNA in these mice. The absence of IL-17 does not alter expression of the antimycobacterial genes, NO synthase 2 and LRG-47, and the absence of IL-23 or IL-17, both of which are implicated in mediating inflammation, fails to substantially affect the granulomatous response to M. tuberculosis infection of the lung. Despite this redundancy, IL-23 is required to provide a moderate level of protection in the absence of IL-12p70, and this protection correlates with a requirement for IL-23 in the IL-12p70-independent induction of Ag-specific, IFN-gamma-producing CD4 T cells. We also show that IL-23 is required for the induction of an IL-17-producing Ag-specific phenotype in naive CD4 T cells in vitro and that absence of IL-12p70 promotes an increase in the number of IL-17-producing Ag-specific CD4 T cells both in vitro and in vivo.