gebhart/patrepeval huggingface dataset:
Preclinical Development Strategies for Novel Gene Therapeutic Products (1999)

With over 220 investigational new drug applications currently active, gene therapy represents one of the fastest growing areas in biotherapeutic research. Initially conceived for replacing defective genes in diseases such as cystic fibrosis or inborn errors of metabolism with genes encoding the normal, or wild-type, gene product, gene therapy has expanded into other novel applications such as treatment of cancer or cardiovascular disease, where the risk:benefit profiles may be more acceptable in relation to the severity of the disease. Different types of vectors, including modified retroviruses, adenoviruses, adenovirus-associated viruses, and herpesviruses and plasmid DNA, are used to transfer foreign genetic material into patients' cells or tissues. Developing a toxicology program to determine the safety of these agents, therefore, requires a modified approach that encompasses the pharmacology and toxicity of both the gene product itself and the vector system used for delivery in the context of the application for the clinical trial. In general, the issues involved in designing and developing appropriate preclinical testing to determine the safety of these products are similar to those encountered for other recombinant molecules, including protein biotherapeutics. Limitations to some of the typical toxicology studies conducted for a traditional drug development program may exist for these agents, and nontraditional approaches may be required to demonstrate their safety. Many factors may affect the safety and clinical activity of these agents, including the route, frequency, and duration of exposure and the type of vector employed. Other safety considerations include quantitation of the duration and degree of expression of the vector in target and other tissues, the effects of gene expression on organ pathology and/or histology, evaluation of trafficking of gene-transduced cells or vector after injection, and interactions of the host immune system with the transduced cell population. Because of the unique concerns regarding each of these therapies, the Center for Biologics Evaluation and Research encourages sponsors to obtain toxicity data whenever possible while evaluating the pharmacologic activity of the vector in a species or animal model relevant to their clinical indication. Sponsors are encouraged to discuss preclinical study design and results with the Center during product development to facilitate early identification of safety concerns prior to entry of these novel agents into the clinical setting and to ensure an uninterrupted course of development while addressing issues required for licensure.
Scoparic Acid A, a β-Glucuronidase Inhibitor from Scoparia dulcis (1992)

The 70% EtOH extract of Scoparia dulcis showed inhibitory activity against beta-glucuronidase from bovine liver. Bioassay-directed fractionation of the active extract led to the isolation of three labdane-type diterpene acids, scoparic acid A [1] [6-benzoyl-12-hydroxy-labda-8(17), 13-dien-18-oic acid], scoparic acid B [2] [6-benzoyl-14,15-dinor-13-oxo-8(17)-labden-18-oic acid], and scoparic acid C [3] [6-benzoyl-15-nor-14-oxo-8(17)-labden-18-oic acid], the structures of which were established by spectral means, including X-ray analysis. Scoparic acid A was found to be a potent beta-glucuronidase inhibitor.
<i>Arabidopsis ALF4</i> encodes a nuclear‐localized protein required for lateral root formation (2004)

Lateral root formation, the primary way plants increase their root mass, displays developmental plasticity in response to environmental changes. The aberrant lateral root formation (alf)4-1 mutation blocks the initiation of lateral roots, thus greatly altering root system architecture. We have positionally cloned the ALF4 gene and have further characterized its phenotype. The encoded ALF4 protein is conserved among plants and has no similarities to proteins from other kingdoms. The gene is present in a single copy in Arabidopsis. Using translational reporters for ALF4 gene expression, we have determined that the ALF4 protein is nuclear localized and that the gene is expressed in most plant tissues; however, ALF4 expression and ALF4's subcellular location are not regulated by auxin. These findings taken together with further genetic and phenotypic characterization of the alf4-1 mutant suggest that ALF4 functions independent from auxin signaling and instead functions in maintaining the pericycle in the mitotically competent state needed for lateral root formation. Our results provide genetic evidence that the pericycle shares properties with meristems and that this tissue plays a central role in creating the developmental plasticity needed for root system development.
Halvade: scalable sequence analysis with MapReduce (2015)

We present Halvade, a framework that enables sequencing pipelines to be executed in parallel on a multi-node and/or multi-core compute infrastructure in a highly efficient manner. As an example, a DNA sequencing analysis pipeline for variant calling has been implemented according to the GATK Best Practices recommendations, supporting both whole genome and whole exome sequencing. Using a 15-node computer cluster with 360 CPU cores in total, Halvade processes the NA12878 dataset (human, 100 bp paired-end reads, 50× coverage) in <3 h with very high parallel efficiency. Even on a single, multi-core machine, Halvade attains a significant speedup compared with running the individual tools with multithreading.
Transformers as Soft Reasoners over Language (2020)

Beginning with McCarthy's Advice Taker (1959), AI has pursued the goal of providing a system with explicit, general knowledge and having the system reason over that knowledge. However, expressing the knowledge in a formal (logical or probabilistic) representation has been a major obstacle to this research. This paper investigates a modern approach to this problem where the facts and rules are provided as natural language sentences, thus bypassing a formal representation. We train transformers to reason (or emulate reasoning) over these sentences using synthetically generated data. Our models, that we call RuleTakers, provide the first empirical demonstration that this kind of soft reasoning over language is learnable, can achieve high (99%) accuracy, and generalizes to test data requiring substantially deeper chaining than seen during training (95%+ scores). We also demonstrate that the models transfer well to two hand-authored rulebases, and to rulebases paraphrased into more natural language. These findings are significant as it suggests a new role for transformers, namely as limited "soft theorem provers" operating over explicit theories in language. This in turn suggests new possibilities for explainability, correctability, and counterfactual reasoning in question-answering.
Proteolytic Activity in Developing Bovine Enamel (1979)

Partially mineralized enamel matrix removed from bovine incisor tooth germs contains proteolytic activity capable of completely degrading enamel matrix proteins at neutral and slightly alkaline pH. The protease activity also degrades common protease substrates such as casein and azocoll with optimal activity at pH 8-9. Inhibitor studies revealed that the enzyme involved is a serine protease of the chymotrypsin family.
Postcrosslinking of macroporous styrene–divinylbenzene copolymers via pendant vinyl groups: Effect of the starting copolymers on the pore structure of the postcrosslinked products (2001)

Abstract In the presence of anhydrous ferric chloride as a Friedel–Crafts catalyst, the postcrosslinking reaction of macroporous styrene–divinylbenzene (St–DVB) copolymers synthesized under different conditions was carried out with 1,2‐dichloroethane as a solvent. Without an externally added crosslinking agent, the specific surface area and pore volume, for copolymers with different DVB isomers or different DVB contents after reaction, in most cases increased significantly, and the increase was found to be heavily dependent upon the amount of the pendant vinyl groups in the starting copolymers. These results further confirm the role of the pendant vinyl groups in creating new crosslinking bonds in addition to those created by a free‐radical crosslinking reaction in the starting copolymers, and an alkylation reaction of the vinyl groups with neighboring aromatic rings is believed to dominate the course of the postcrosslinking at a relatively high level of the vinyl group contents. The synthesis conditions, including the n ‐heptane content in a mixed diluent and the amount of the diluent, under which the starting copolymers were synthesized, play an important role in the increase of the surface area and pore volume of the copolymers after postcrosslinking. The effect of these conditions is attributed mainly to the swelling ability of the starting copolymers thus obtained in the solvent used for reaction. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 83: 1668–1677, 2002
Dissolution Inhibition of Phenolic Resins by Diazonaphthoquinone: Effect of Polymer Structure (1991)

In order to understand the basic mechanisms working in the dissolution of phenolic resin/diazonaphthoquinone (DNQ) positive photoresists, several polyhydroxystyrene derivatives have been studied in terms of their dissolution capabilities. The influence of the structure and the molecular weight distributions of phenolic resins on the inhibition effect were examined. In phenolic resins which have alkyl groups ortho to the hydroxy group a strong dissolution inhibition effect is found. As for the molecular weight distribution, the mixtures of a higher-molecular-weight polymer with lower dissolution rate and a lower-molecular-weight polymer with higher dissolution rate give strong dissolution inhibition by DNQ.
In‐situ biological oxidation of hazardous organics (1984)

Abstract Colloidal gas aphrons show good adhesion and retention in unconsolidated saturated soil matrices.
Accuracy of tablet splitting and liquid measurements: an examination of who, what and how (2016)

Formulation characteristics and manipulation technique have greater influences on the accuracy of medication modification and should be considered in off-label drug use in vulnerable populations.
An Outbreak of Febrile Gastroenteritis Associated with Corn Contaminated by<i>Listeria monocytogenes</i> (2000)

Food-borne infection with L. monocytogenes can cause febrile illness with gastroenteritis in immunocompetent persons.
Activation of the granule pool of the NADPH oxidase accelerates apoptosis in human neutrophils (1999)

Oxidative stress induces apoptosis in many types of cells, including human neutrophils. Our objective was to determine whether reactive oxygen species (ROS) produced by activated neutrophils are associated with accelerated apoptosis. Exposing neutrophils to ionomycin or phorbol myristate acetate (PMA) induced intracellular H2O2 production and rapid onset of apoptosis, measured as condensed chromatin, cellular shrinkage, and DNA fragmentation. Neutrophils activated with formyl-methionyl-leucyl-phenylalanine (fMLP) generated mainly extracellular H2O2 and did not undergo apoptosis. Exogenously added H2O2, together with the catalase blocker sodium azide, induced apoptosis to the same extent and with similar kinetics as PMA and ionomycin. Adenosine inhibited ionomycin-induced intracellular H2O2 production and apoptosis. Neither PMA nor ionomycin caused apoptosis in dimethyl sulfoxide-differentiated HL-60 cells, which are incapable of intracellular H2O2 production, whereas H2O2 induced apoptosis more efficiently in these cells than in neutrophils. We propose that activated neutrophils use intracellularly formed H2O2 to commit suicide.
Direct Electroplating of Lithium Cobalt Oxide Film on Platinum Substrate in 100°–200°C Aqueous Solution (2002)

Well crystallized, shape‐formed, and electrochemically active lithium cobalt oxide (LiCoO 2 ) films are electroplated directly on an electron‐conducting substrate in an aqueous solution using a soft solution processing that is economical, consumes less energy consuming, and is environmentally friendly. Although LiCoO 2 films are easily and economically prepared without any post‐synthesis heat treatment, the estimated film properties show a possibility of using the deposited films as a cathode film for lithium rechargeable microbatteries. In addition, the soft solution processing reveals that an exact understanding of chemical reactions and the proper combination of the chemical reactions can create an advanced synthetic procedure.
Seismic behavior of high-performance fiber reinforced cementitious composite coupling beams. (2004)

Coupling beams may significantly improve the seismic behavior of structural wall systems, depending on their span-to-depth ratio and their ability to transfer shear between coupled walls during earthquake ground motions. Current design requirements for deep reinforced concrete (RC) coupling beams include intricate diagonal reinforcement detailing to ensure a stable behavior during earthquakes, leading to reinforcement congestion and construction difficulties. A research program was conducted at the University of Michigan to develop a simple design for coupling beams through the use of strain-hardening or high-performance fiber reinforced cement composites (HPFRCCs). Four coupling beam specimens were tested, including an RC control specimen. Specimens were proportioned to approximately 3/4 of full scale and a span-to-depth ratio of l.0 was selected to ensure a shear dominant behavior. The main variables investigated were the type of material used in the coupling beams, fiber type, and reinforcement detailing. The HPFRCC beams were cast separately as prefabricated members to ensure adequate material quality and to ease the construction process at the job site. Test results indicate that in order to achieve a large displacement capacity, diagonal reinforcement must be used in the proposed HPFRCC coupling beams. However, the use of strain-hardening fiber composites allowed the elimination of transverse reinforcement required for confinement in RC coupling beams, thus significantly simplifying the reinforcement details. In the analytical phase of the research program, a method to predict the shear force versus shear distortion envelope curve of HPFRCC coupling beams was developed. Key shear distortion levels were predicted based on the tensile strain capacity of the HPFRCC material. The corresponding shear strength was estimated based on the contributions from the HPFRCC material and steel reinforcement. Using the predicted envelope curve, an existing hysteretic model was modified to accurately simulate the behavior of HPFRCC coupling beams under displacement reversals. As a result, good agreement between the predicted and experimental response was obtained. In the final phase of the analytical study, a damage index analysis was performed and a range of values was proposed to predict the performance of HPFRCC coupling beams during earthquakes.
Effects of Sowing Time and Growing Density on Agronomic Traits, Grain Yield, and Grain Quality of Waxy Sorghum Cultivar Hongliangfeng 1 (2019)

The aim of this study was to determine the effects of sowing time and growing density on the yield and quality of grain in waxy sorghum (Sorghum bicolor L. Moench). The main plots were two sowing time: early sowing (5 April) and late sowing (20 April), and the subplots were three growing densities: 0.8 &times; 105, 1.1 &times; 105, and 1.4 &times; 105 plants/ha. Results showed that sowing time and growing density had significant effects on grain yield and grain quality of waxy sorghum cultivar Hongliangfeng 1. Grain yield, plant height, spike length, culm diameter, grain number per spike, grain weight per plant, 1000-grain weight, protein content, starch content, and amylopectin content were reduced by a delay of sowing time, while the tannin content and amylose content were increased by a delay of sowing time. Grain yield, plant height, spike length, culm diameter, grain number per spike, grain weight per plant, 1000-grain weight, protein content, starch content, and amylopectin content increased and then decreased with the increase of growing density, while the tannin content and amylose content decreased and then increased with the increase of growing density. These results hinted that appropriate sowing time and growing density are key cultivation measures to ensure high yield and good quality&nbsp;in waxy sorghum production.
Discriminative word-spotting using ordered spectro-temporal patch features. (2008)

We present a novel architecture for word-spotting which is trained from a small number of examples to classify an utterance as containing a target keyword or not. The word-spotting architecture relies on a novel feature set consisting of a set of ordered spectro-temporal patches which are extracted from exemplar mel-spectra of target keywords. A local pooling operation across frequency and time is introduced which endows the extracted patch features with the flexibility to match novel
Si as a diffusion barrier for Ge/GaAs heterojunctions (1990)

We compare the electrical characteristics, before and after annealing, of p-Ge/N-GaAs heterojunction diodes to similar diodes which incorporate a nominally 10 Å layer of pseudomorphic Si at the Ge/GaAs interface. Both types of diodes exhibit excellent current-voltage characteristics before annealing. Diodes having no Si interlayer show significant degradation after a 20 min anneal at 640 °C. Diodes incorporating the Si interlayer retain excellent diode characteristics after a 20 min anneal at temperatures as high as 720 °C.
Intraperitoneal immunotherapy with T cells stably and transiently expressing anti-EpCAM CAR in xenograft models of peritoneal carcinomatosis (2017)

// Wei Xia Ang 1, 2, * , Zhendong Li 1, * , Zhixia Chi 1 , Shou-Hui Du 1 , Can Chen 3 , Johan C.K. Tay 1 , Han Chong Toh 4 , John E. Connolly 5 , Xue Hu Xu 6 , Shu Wang 1, 2 1 Department of Biological Sciences, National University of Singapore 117543, Singapore 2 Institute of Bioengineering and Nanotechnology 138669, Singapore 3 Tessa Therapeutics, Pte Ltd., 239351, Singapore 4 Division of Medical Oncology, National Cancer Centre, 169610, Singapore 5 Programme in Translational Immunology, Institute for Molecular and Cell Biology 138648, Singapore 6 Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China * The authors contributed equally to these work Correspondence to: Shu Wang, email: dbsws@nus.edu.sg Keywords: peritoneal carcinomatosis, EpCAM, chimeric antigen receptor, T lymphocytes, adoptive immunotherapy Received: June 16, 2016      Accepted: January 03, 2017      Published: January 10, 2017 ABSTRACT The epithelial cell adhesion molecule (EpCAM) is overexpressed in a wide variety of tumor types, including peritoneal carcinomatosis (PC) from gastrointestinal and gynecological malignancies. To develop a chimeric antigen receptor T (CART) cell therapy approach to treat patients with end-stage PC, we constructed third generation CARs specific to EpCAM using the 4D5MOC-B single chain variable fragment. CART cells were generated with lentiviral transduction and exhibited specific in vitro killing activity against EpCAM-positive human ovarian and colorectal cancer cells. A single intraperitoneal injection of the CART cells eradicated established ovarian xenografts and resulted in significantly prolonged animal survival. Since EpCAM is also expressed on normal epithelium, anti-EpCAM CART cells were generated by mRNA electroporation that display a controlled cytolytic activity with a limited CAR expression duration. Multiple repeated infusions of these RNA CAR-modified T cells delayed disease progression in immunodeficient mice bearing well-established peritoneal ovarian and colorectal xenografts. Thus, our study demonstrates the effectiveness of using anti-EpCAM CAR-expressing T cells for local treatment of PC in mice. The possibility of using this approach for clinical treatment of EpCAM-positive gastrointestinal and gynecological malignancies warrants further validation.
PICNIC: an algorithm to predict absolute allelic copy number variation with microarray cancer data (2009)

High-throughput oligonucleotide microarrays are commonly employed to investigate genetic disease, including cancer. The algorithms employed to extract genotypes and copy number variation function optimally for diploid genomes usually associated with inherited disease. However, cancer genomes are aneuploid in nature leading to systematic errors when using these techniques. We introduce a preprocessing transformation and hidden Markov model algorithm bespoke to cancer. This produces genotype classification, specification of regions of loss of heterozygosity, and absolute allelic copy number segmentation. Accurate prediction is demonstrated with a combination of independent experimental techniques. These methods are exemplified with affymetrix genome-wide SNP6.0 data from 755 cancer cell lines, enabling inference upon a number of features of biological interest. These data and the coded algorithm are freely available for download.
Regulation of matrix metalloproteinase-1 by Epstein-Barr virus proteins. (2003)

Matrix metalloproteinases (MMPs) play crucial roles in tumor progression. To investigate the roles of MMPs in the progression of nasopharyngeal carcinoma (NPC), the expression of MMP-1, MMP-2, MMP-3, MMP-7, MMP-12, MMP-13, MMP-14, and MMP-19 was explored by microarray assay. Among them, MMP-1 was significantly up-regulated in NPC biopsies. These results were confirmed further by real-time quantitative PCR in additional NPC biopsies and comparison with normal tissues and other head and neck cancers. Moreover, the use of RNA from different cellular constituents of NPC biopsies revealed that MMP-1 was detected predominantly in epithelial cells. Immunohistochemical staining of paraffin-fixed NPC sections confirmed that MMP-1 protein was expressed in the epithelial tumor cells. Because EBV is strongly associated with NPC formation, we sought a correlation between viral gene expression and MMP-1 up-regulation. The results showed clearly that the amounts of transcripts, proteins, and enzyme activities of MMP-1 were increased in cells expressing EBV proteins, LMP1 (latent membrane protein 1) and Zta (Z transactivator; also named as BZLF1 or ZEBRA) but not EBNA-1 (EBV nuclear antigen-1). Additionally, the mobility of LMP1 and Zta transfectants was increased in scrape-wound migration assays. The invasiveness and ability to survive in a three-dimensional collagen gel also were enhanced in LMP1- and Zta-expressing cells. Furthermore, anti-MMP-1 antibody and peptide inhibitors could block the invasiveness and survival properties of LMP1 and Zta transfectants, suggesting a real contribution of MMP-1 to cell mobility and survival. Taken together, our data show that the viral LMP1 and Zta proteins regulate the expression and activity of MMP-1, and thereby confer the invasive properties of the cells. This study presents the first evidence that viral proteins are capable of regulating MMP-1 and also provides clues for the role of EBV in NPC progression.
Trimethylaluminum (TMA)-Catalyzed Reaction of Alkynyllithiums with Ethylene Oxide: Increased Yields and Purity of Homopropargylic Alcohols (2005)

An efficient protocol was developed to obtain homo­propargylic alcohols. Subjecting alkynyllithiums and ethylene ­oxide to 10-20 mol% of trimethylaluminum provided homopro­pargylic alcohols in good yields.