gebhart/patrepeval huggingface dataset:
Tethering: Fragment-Based Drug Discovery (2004)

The genomics revolution has provided a deluge of new targets for drug discovery. To facilitate the drug discovery process, many researchers are turning to fragment-based approaches to find lead molecules more efficiently. One such method, Tethering1, allows for the identification of small-molecule fragments that bind to specific regions of a protein target. These fragments can then be elaborated, combined with other molecules, or combined with one another to provide high-affinity drug leads. In this review we describe the background and theory behind Tethering and discuss its use in identifying novel inhibitors for protein targets including interleukin-2 (IL-2), thymidylate synthase (TS), protein tyrosine phosphatase 1B (PTP-1B), and caspases.
Recent development in 2‐pyrrolidinone‐containing nootropics (1989)

Abstract This paper reviews the development of the concept of nootropics‐‐compounds whose activity appears to be specific to enhancement and protection of those functions of plasticity of the central nervous system that we now call cognition. The rest of the review focuses on clinical and preclinical results reported on 2‐pyrrolidinone‐containing noortropics since 1986. Although the clinical efficacy of these compounds remains to be proved definitively, there are some double‐blind trials that demonstrate superiority against placebo. Preclinically, a wide variety of laboratories continue to demonstrate and expand protective effects of nootropics against various insults of the CNS.
LOUD: A 1020 node Microphone Array and Acoustic Beamformer (2007)

Abstract : Recording speech and other sound is difficult in environments with a large amount of noise and/or crosstalk. In these environments, array microphones are needed in order to obtain a clean recording of desired speech. In this work, we have designed, implemented, and tested LOUD,a 1020-node microphone array. To the best of our knowledge and as documented by Guinness World Records [6], this is currently the largest microphone array in the world. We have implemented an acoustic beamforming algorithm for sound source amplification in a noisy environment, and have obtained preliminary results demonstrating the efficacy of the array. From one to 1020 microphones, we have shown a 13.7dB increase in peak SNR for a representative utterance, an 87.2 drop in word error rate (WER) with interferer present, and an 91.3 drop in WER without an interferer.
Semi-Supervised Sequential Labeling and Segmentation Using Giga-Word Scale Unlabeled Data (2008)

This paper provides evidence that the use of more unlabeled data in semi-supervised learning can improve the performance of Natural Language Processing (NLP) tasks, such as part-of-speech tagging, syntactic chunking, and named entity recognition. We first propose a simple yet powerful semi-supervised discriminative model appropriate for handling large scale unlabeled data. Then, we describe experiments performed on widely used test collections, namely, PTB III data, CoNLL’00 and ’03 shared task data for the above three NLP tasks, respectively. We incorporate up to 1G-words (one billion tokens) of unlabeled data, which is the largest amount of unlabeled data ever used for these tasks, to investigate the performance improvement. In addition, our results are superior to the best reported results for all of the above test collections. 1
Characterization of a Recombinant Adeno-Associated Virus Type 2 Reference Standard Material (2010)

A recombinant adeno-associated virus serotype 2 Reference Standard Material (rAAV2 RSM) has been produced and characterized with the purpose of providing a reference standard for particle titer, vector genome titer, and infectious titer for AAV2 gene transfer vectors. Production and purification of the reference material were carried out by helper virus-free transient transfection and chromatographic purification. The purified bulk material was vialed, confirmed negative for microbial contamination, and then distributed for characterization along with standard assay protocols and assay reagents to 16 laboratories worldwide. Using statistical transformation and modeling of the raw data, mean titers and confidence intervals were determined for capsid particles ({X}, 9.18 x 10¹¹ particles/ml; 95% confidence interval [CI], 7.89 x 10¹¹ to 1.05 x 10¹² particles/ml), vector genomes ({X}, 3.28 x 10¹⁰ vector genomes/ml; 95% CI, 2.70 x 10¹⁰ to 4.75 x 10¹⁰ vector genomes/ml), transducing units ({X}, 5.09 x 10⁸ transducing units/ml; 95% CI, 2.00 x 10⁸ to 9.60 x 10⁸ transducing units/ml), and infectious units ({X}, 4.37 x 10⁹ TCID₅₀ IU/ml; 95% CI, 2.06 x 10⁹ to 9.26 x 10⁹ TCID₅₀ IU/ml). Further analysis confirmed the identity of the reference material as AAV2 and the purity relative to nonvector proteins as greater than 94%. One obvious trend in the quantitative data was the degree of variation between institutions for each assay despite the relatively tight correlation of assay results within an institution. This relatively poor degree of interlaboratory precision and accuracy was apparent even though attempts were made to standardize the assays by providing detailed protocols and common reagents. This is the first time that such variation between laboratories has been thoroughly documented and the findings emphasize the need in the field for universal reference standards. The rAAV2 RSM has been deposited with the American Type Culture Collection and is available to the scientific community to calibrate laboratory-specific internal titer standards. Anticipated uses of the rAAV2 RSM are discussed.
Efficient Oncogene Silencing and Metastasis Inhibition via Systemic Delivery of siRNA (2008)

The selective delivery of small interfering RNA (siRNA) to metastatic tumors remains a challenging task. We have developed a nanoparticle (NP) formulation composed of siRNA, a carrier DNA, a polycationic peptide, and cationic liposomes. The NP was obtained by a self-assembling process, followed by surface modification with a polyethylene glycol (PEG)-conjugated ligand, anisamide. The NP was PEGylated and a ligand was presented to target sigma receptor-expressing murine melanoma cells, B16F10. The lung metastasis model was established by intravenous (i.v.) injection of the B16F10 cells into C57BL/6 mice. A mixture of siRNA against MDM2, c-myc, and vascular endothelial growth factor (VEGF) co-formulated in the targeted NP caused simultaneous silencing of each of the oncogenes in the metastatic nodules. Two consecutive i.v. injections of siRNA in the targeted NP significantly reduced the lung metastasis (approximately 70-80%) at a relatively low dose (0.45 mg/kg), whereas free siRNA and the nontargeted NP showed little effect. This targeted NP formulation significantly prolonged the mean survival time of the animals by 30% as compared to the untreated controls. At the therapeutic dose, the targeted NP showed little local and systemic immunotoxicity and did not decrease the body weight or damage the major organs.
The isolation and characterization of a barley 1,3‐1,4‐β‐glucanase gene (1990)

The barley gene encoding isozyme I of 1,3-1,4-beta-glucanase was isolated and sequenced. The 6260-bp region sequenced included 1885 bp of the 5'-flanking region, the entire coding region, an intron of 2490 bp, and 792 bp of the 3'-flanking region. The 1,3-1,4-beta-glucanase mRNA was found to be regulated at the level of RNA accumulation by both gibberellins (positively) and abscisic acid (negatively) in barley aleurones. The mRNA for isozyme II preferentially accumulated (70%) relative to the mRNA for isozyme I (30%) in poly(A)-rich RNA isolated from material including both the aleurone and the scutellum tissues. The gene family encoding 1,3-1,4-beta-glucanase enzymes in barley was found to be comprised of two closely related genes, isozymes I and II, as well as several related sequences that could be identified by Southern blot analysis. The nucleotide sequence for the 5' untranslated leader and the coding region for the signal peptide of the isozyme II transcript were determined from a cDNA produced by the polymerase chain reaction. The structure of the protein encoded by the isozyme I gene is also discussed.
In vivo delivery of small interfering RNA to tumors and their vasculature by novel dendritic nanocarriers (2010)

New targets for RNA interference (RNAi)-based cancer therapy are constantly emerging from the increasing knowledge on key molecular pathways that are paramount for carcinogenesis. Nevertheless, in vivo delivery of small interfering RNA (siRNA) remains a crucial challenge for therapeutic success. siRNAs on their own are not taken up by most mammalian cells in a way that preserves their activity. Moreover, when applied in vivo, siRNA-based approaches are all limited by poor penetration into the target tissue and low silencing efficiency. To circumvent these limitations, we have developed novel polymerized polyglycerol-based dendrimer core shell structures to deliver siRNA to tumors in vivo. These cationic dendrimers can strongly improve the stability of the siRNA, its intracellular trafficking, its silencing efficacy, and its accumulation in the tumor environment owing to the enhanced permeability and retention effect. Here, we show that our dendritic nanocarriers exhibited low cytotoxicity and high efficacy in delivering active siRNA into cells. With use of human glioblastoma and murine mammary adenocarcinoma cell lines as model systems, these siRNA-dendrimer polyplexes silenced the luciferase gene, ectopically overexpressed in these cells. Importantly, significant gene silencing was accomplished in vivo within 24 h of treatment with our luciferase siRNA-nanocarrier polyplexes, as measured by noninvasive intravital bioluminescence imaging. Moreover, our siRNA-nanocarriers show very low levels of toxicity as no significant weight loss was observed after intravenous administration of the polyplexes. We show a proof of concept for siRNA delivery in vivo using a luciferase-based model. We predict that in vivo silencing of important cell growth and angiogenesis regulator genes in a selective manner will justify this approach as a successful anticancer therapy.
Trust in Cyberspace (1999)

At a 27 October news conference, the National Research Council (NRC) unveiled a study called ‘Trust in Cyberspace’ commissioned by the NSA and the Defense Advanced Research Projects Agency (DARPA), the study by the Committee on Information Systems Trustworthiness, a panel composed of several leading industry specialists and academics, concluded that all the work done heretofore by NSA, the Communications Security Establishment (CSE) of Canada, and a group of four European countries on information security standards, has been largely fruitless.
Prognostic and predictive markers in pancreatic adenocarcinoma (2015)

Pancreatic ductal adenocarcinoma is characterized by a poor prognosis and a low median survival, despite improvements observed for many other solid tumours. Intensive research efforts have been undertaken during the last decades to discover new prognostic and treatment predictive biomarkers for pancreatic ductal adenocarcinoma. The mainstay of medical treatment for the disease has been the well-tolerated nucleoside analogue, gemcitabine. The only targeted agent currently used in pancreatic ductal adenocarcinoma patients is the epithelial growth factor receptor inhibitor erlotinib in combination with gemcitabine. Recently, treatment regimens such as a combination of fluorouracil-leucovorin-irinotecan-oxaliplatin (FOLFIRINOX) and the combination of nab-paclitaxel with gemcitabine have been introduced for metastatic pancreatic ductal adenocarcinoma. Although these treatment regimens significantly improve survival of patients, there are no good predictive biomarkers available that can be used to identify who would benefit most from them. Therefore, the search for predictive biomarkers that would facilitate personalization of chemotherapy is highly relevant.
Emulsion-based Drug Delivery Systems (2004)

A new solid-in-oil-in-water (S/O/W) emulsion consisting of edible surfactants, an edible oil, and a water-soluble drug has been developed for oral administration of peptide/protein drugs. Insulin, which is a hydrophilic macromoleclule, was converted into a lipophilic complex using edible surfactants. As the resultant complex can be directly solubilized in the oil phase, surfactant-insulin complexes can be incorporated into the oil phase of oil-in-water emulsions, allowing the formulation of stable S/O/W emulsions. The capability of S/O/W emulsions in the control of blood glucose was investigated with diabetic model rats. The glucose level in the serum slowly decreased over several hours when the S/O/W emulsions were orally administered, while the aqueous solution of insulin (as the control) showed no significant effect on the blood glucose level. The hypoglycemic effect of surfactant-insulin complex incorporated into the S/O/W emulsions and the stable encapsulation of insulin into dry emulsion formulations will offer one way to oral delivery of biopharmaceuticals.
Regulation of indoleamine 2,3-dioxygenase gene expression in human fibroblasts by interferon-gamma. Upstream control region discriminates between interferon-gamma and interferon-alpha. (1990)

The interferon (IFN)-gamma-mediated induction of indoleamine 2,3-dioxygenase (IDO) enzyme, which converts tryptophan into N-formylkynurenine, has been implicated in the inhibition of intracellular pathogens, e.g. Toxoplasma gondii and Chlamydia psittaci, and in the antiproliferative effect of IFN-gamma on tumor cells. The IDO activity is induced strongly in many cell types by IFN-gamma but rather poorly by IFN-alpha or -beta. A genomic DNA clone containing part of the transcribed region of the IDO gene and approximately 13 kilobases (kb) of the 5'-upstream DNA sequence was isolated and analyzed. An approximately 1.4-kb fragment of this clone, containing 329 nucleotides of the transcribed sequence and approximately 1.1 kb of the 5'-upstream sequence, when ligated to chloramphenicol acetyltransferase (CAT) structural gene made its expression inducible by IFN-gamma, but this construct responded poorly, if at all, to IFN-alpha 2. Deletion constructs derived from this plasmid narrowed down the IFN-gamma-responsive region to a 151-nucleotide segment (-495/-344) which also contained a 14-nucleotide sequence (GGTTTCAGTTTTCC) highly homologous to the IFN(alpha)-stimulated response element (ISRE) that has been found so far in all cellular genes inducible with IFN-alpha or -beta. Expression of CAT activity was stimulated by IFN-gamma more effectively than by IFN-alpha 2 when a 155-nucleotide fragment (-495/-340) containing the 151-nucleotide segment required for IFN-gamma response was inserted before herpes simplex virus thymidine kinase promoter linked to CAT structural gene. The results indicate that despite the presence of an ISRE, the control region of the IDO gene can distinguish between IFN-gamma and IFN-alpha. This may account for the differential activation of IDO gene expression by IFN-gamma as against IFN-alpha or -beta in intact cells, and suggests that the response of ISRE to IFN-alpha or -beta may be governed by other features in the upstream control region of this gene.
Translation Unit Concerning Timing of Simultaneous Translation. (2002)

This paper discusses and proposes a translation unit for simultaneous translation using a machine translation (MT) system. Monologues, such as lectures or broadcast news, are used as the target of simultaneous speech translation. To date, a lot of research on speech translation has dealt with dialogues, especially travel conversations. Most of the speech translation systems in MT have treated a sentence as a translation unit. In the ATR travel conversation database, sentence length is less than 10 words on average. Therefore, most of the sentences are simple and almost all of the utterances are constructed in one or two sentences. However, the sentences of monologues are longer than travel dialogues. They have over 30 words (as in “ASU-wo-YOMU, ” a TV news commentary program) on average, and most of the sentences are complex or compound. Accordingly, it is difficult to treat a sentence as a translation unit for monologues, and thus an appropriate translation unit needs to be found. Considering this, we hypothesized that an adequate translation unit of speech translation systems relates to the translation unit of a human simultaneous translator. Therefore, we collected simultaneous translation data from lectures by human translators and investigated the characteristics of monologues and simultaneous translation. 1.
In vivo determination of skin surface topography using an optical 3D device (2004)

The results show a significant dependence of the skin surface topography on the age of the volunteer and the body site measured. Particularly the waviness, the Fourier analysis and the furrow profiles reflect such dependencies. The system used also fulfils the requirements for the testing of therapies, as was demonstrated by the reduction of mimic wrinkles after treatment with botulinum Toxin A.
Protein-conjugated, glucose-sensitive surface using fluorescent dendrimer porphyrin (2009)

A multi-functional dendrimer-coated surface has been prepared for the effective protein immobilization and detection of protein activity. The silicon surface was first modified with positively-charged amino groups using 3-aminopropyltriethoxysilane (APTES), and subsequently coated with ionic dendrimer porphyrin (DP) by electrostatic interaction. Fluorescence and atomic force microscopy (AFM) studies showed that the dendrimer was homogeneously coated on the APTES-modified silicon surface as dome-shaped features that protruded 1.0–2.5 nm above the surface and had diameters ranging from 50 nm to 100 nm. The dendrimer-modified surface showed a higher capacity to covalently bind proteins, compared to the control surfaces, and the protein activity was higher by a factor of two. Using the fluorescent property of the porphyrin core, the relative amounts of dendrimer and the enzyme-catalyzed reactions on the dendrimer-coated surface were examined by fluorescence microscopy. Glucose oxidase (GOX)-mediated glucose oxidation quenched fluorescence emission from the focal porphyrin core through a peroxidase-coupled system and from the quantitative relationship between quenching and glucose concentration, the GOX-catalyzed reaction could be characterized.
Purification, characterization and complete amino acid sequence of nuclease Cl from Cunninghamella echinulata var. echinulata (1998)

It is known, from the zymogram method of nuclease activity assay, that the crude extracts of Cunninghamella echinulata var. echinulata contained at least three distinct extracellular nucleases. Among them, the major form was 30 kDa in molecular mass and termed nuclease C1. In this report, nuclease C1 was purified to apparent homogeneity by chromatography on Cibacron blue-3GA, phenyl-Sepharose 4B and HiTrap Heparin. Nuclease C1 acquired enzymatic activity in the presence of Mn2+ or Mg2+ and was inhibited by EDTA. The activity was maximal at pH 7-8.5. The primary structure of nuclease C1 was completely determined using enzymatic digestion and gene cloning. The N-terminal 49 residues of nuclease C1 were first elucidated from a tryptic digest. Two degenerate upstream primers were subsequently designed to amplify the cDNA encoding nuclease C1. The resulting protein sequence of nuclease C1 was shown to be composed of 252 residues. It was intriguing to find that the protein sequence of nuclease C1 showed significant similarities with the sequences of the mitochondrial nucleases of Saccharomyces cerevisiae (44% identity) and Schizosaccharomyces pombe (42% identity). Residue His87 of nuclease C1 was postulated to be located at the active site from sequence similarity with secreted nuclease from Serratia marcescens.
Cytogenetic and expression profiles associated with transformation to androgen-resistant prostate cancer (2005)

Our findings may serve as a basis for molecular dissection of the mechanisms involved in development of androgen resistant prostate cancer.
Global Molecular and Morphological Effects of 24-Hour Chromium(VI) Exposure on Shewanella oneidensis MR-1 (2006)

The biological impact of 24-h ("chronic") chromium(VI) [Cr(VI) or chromate] exposure on Shewanella oneidensis MR-1 was assessed by analyzing cellular morphology as well as genome-wide differential gene and protein expression profiles. Cells challenged aerobically with an initial chromate concentration of 0.3 mM in complex growth medium were compared to untreated control cells grown in the absence of chromate. At the 24-h time point at which cells were harvested for transcriptome and proteome analyses, no residual Cr(VI) was detected in the culture supernatant, thus suggesting the complete uptake and/or reduction of this metal by cells. In contrast to the untreated control cells, Cr(VI)-exposed cells formed apparently aseptate, nonmotile filaments that tended to aggregate. Transcriptome profiling and mass spectrometry-based proteomic characterization revealed that the principal molecular response to 24-h Cr(VI) exposure was the induction of prophage-related genes and their encoded products as well as a number of functionally undefined hypothetical genes that were located within the integrated phage regions of the MR-1 genome. In addition, genes with annotated functions in DNA metabolism, cell division, biosynthesis and degradation of the murein (peptidoglycan) sacculus, membrane response, and general environmental stress protection were upregulated, while genes encoding chemotaxis, motility, and transport/binding proteins were largely repressed under conditions of 24-h chromate treatment.
Photostability of Colloidal PbSe and PbSe/PbS Core/Shell Nanocrystals in Solution and in the Solid State (2006)

The photostability of semiconductor PbSe nanocrystals (NCs) under different storage conditions and the photoluminescence of PbSe NC films on Si substrates under vacuum and under different atmospheres were investigated. The NCs show a small blue shift in both the emission and absorption spectra when stored in solution. This blue shift is accelerated when the particles are stored in room light compared to when the particles are stored in the dark, which indicates that photooxidation is an important process. The photooxidation process is accelerated by irradiating NC solutions with a 450 W xenon lamp. The photobleaching and appearance of a precipitate are attributed to ligand desorption followed by agglomeration. Reversible O2-induced luminescence quenching was observed on a PbSe NC film on Si substrates, which could be addressed by two mechanisms: indirect quenching by alteration of PbSe charging and neutralization dynamics or quenching through direct interaction of O2 with the exciton. To improve the photostability of PbSe NCs, PbSe/PbS core/shell NCs using (TOP)S (TOP = trioctylphosphine) and TMS2S (TMS2 = bis(trimethylsilyl)) as sulfur sources were prepared. However, PbSe/PbS core/shell NCs did not show an increased stability in solution upon irradiation with a xenon lamp when compared with PbSe core NCs. Either the PbS shell is not able to confine the charge carriers or there is incomplete shell passivation with the PbSe core, and as a result these core/shell NCs have comparable stability.