gebhart/patrepeval huggingface dataset:
Regulation of Lymphocyte Cell Fate Decisions and Lymphomagenesis by BCL-6 (1999)

Genetic alterations of the BCL-6 gene in mice and man have established BCL-6 as a pivotal regulator of normal differentiation of B and T lymphocytes as well as one of the most frequently translocated oncogenes in human B cell lymphomas. As an oncogene, BCL-6 has not been easy to place into existing paradigms of cellular transformation. Rather, it is likely that the function of BCL-6 as a regulator of lymphocyte differentiation is subverted in BCL-6-induced lymphomas. The lymphomas in which BCL-6 is translocated are all suspected to arise from the germinal center B lymphocyte. Given the selective expression of BCL-6 protein in normal germinal center B lymphocytes and the requirement for BCL-6 in germinal center development, the functions of BCL-6 in normal and malignant B cells are probably intertwined. The BCL-6 protein is a potent transcriptional repressor which presumably controls lymphocyte differentiation and induces lymphomas by regulating the expression of key downstream target genes.
Selective thyroid hormone receptor modulators (2013)

Thyroid hormone (TH) is known to have many beneficial effects on vital organs, but its extrapolation to be used therapeutically has been restricted by the fact that it does have concurrent adverse effects. Recent finding of various thyroid hormone receptors (TR) isoforms and their differential pattern of tissue distribution has regained interest in possible use of TH analogues in therapeutics. These findings were followed by search of compounds with isoform-specific or tissue-specific action on TR. Studying the structure-activity relationship of TR led to the development of compounds like GC1 and KB141, which preferentially act on the β1 isoform of TR. More recently, eprotirome was developed and has been studied in humans. It has shown to be effective in dyslipidemia by the lipid-lowering action of TH in the liver and also in obesity. Another compound, 3,5-diiodothyropropionic acid (DITPA), binds to both α- and β-type TRs with relatively low affinity and has been shown to be effective in heart failure (HF). In postinfarction models of HF and in a pilot clinical study, DITPA increased cardiac performance without affecting the heart rate. TR antagonists like NH3 can be used in thyrotoxicosis and cardiac arrhythmias. However, further larger clinical trials on some of these promising compounds and development of newer compounds with increased selectivity is required to achieve higher precision of action and avoid adverse effects seen with TH.
Problem Determination in Enterprise Middleware Systems using Change Point Correlation of Time Series Data (2006)

Clustered enterprise middleware systems employing dynamic workload scheduling are susceptible to a variety of application malfunctions that can manifest themselves in a counterintuitive fashion and cause debilitating damage. Until now, diagnosing problems in that domain involves investigating log files and configuration settings and requires in-depth knowledge of the middleware architecture and application design. This paper presents a method for problem determination using change point detection techniques and problem signatures consisting of a combination of changes (or absence of changes) in different metrics. We implemented this approach on a clustered middleware system and applied it to the detection of the storm drain condition: a debilitating problem encountered in clustered systems with counterintuitive symptoms. Our experimental results show that the system detects 93% of storm drain faults with no false positives.
Effects of Buy Korean Sentiment on Consumers and Firms (2000)

This paper analyzes the effects of Buy Korean sentiment on consumers and firms. Given the cultural belief of Buy Korean, signals of Buy Korean sent by the society effectively appeal to consumers who respond by purchasing the domestic rather than imported goods. The main contribution of this paper is to endogenize Buy Korean effects into a simple model. Bias toward the domestic tends to increase the equilibrium profits of the domestic firm. However, signal regime may lead to a higher equilibrium price of the domestic than in case of no signal regime. Furthermore, no signal regime is relatively efficient in inducing R&D for the domestic finn. Signal regime may deteriorate incentives to undertake R&D by the domestic since the foreign firm has incentives to spoil this attempt by the domestic firm. This paper concludes with future research agenda.
nanoLAB: An ultraportable, handheld diagnostic laboratory for global health (2011)

Driven by scientific progress and economic stimulus, medical diagnostics will move to a stage in which straightforward medical diagnoses are independent of physician visits and large centralized laboratories. The future of basic diagnostic medicine will lie in the hands of private individuals. We have taken significant strides towards achieving this goal by developing an autoassembly assay for disease biomarker detection which obviates the need for washing steps and is run on a handheld sensing platform. By coupling magnetic nanotechnology with an array of magnetically responsive nanosensors, we demonstrate a rapid, multiplex immunoassay that eliminates the need for trained technicians to run molecular diagnostic tests. Furthermore, the platform is battery-powered and ultraportable, allowing the assay to be run anywhere in the world by any individual.
Regulation of motility in bovine brain endothelial cells (1991)

Scatter factor (SF) is a fibroblast-derived cytokine which stimulates motility of epithelial and vascular endothelial cells. We used a quantitative assay based on migration of cells from microcarrier beads to flat surfaces to study the regulation of motility in bovine brain endothelial cells (BBEC). Peptide growth factors (EGF, ECGF, basic FGF) did not stimulate migration. Tumor promoting phorbol esters (PMA, PDD) markedly stimulated migration, while inactive phorbol esters (4a-PDD, phorbol-13,20-diacetate) did not affect migration. Both SF- and PMA-stimulated migration were inhibited by 1) TGF-beta; 2) protein kinase inhibitors (e.g., staurosporine, K-252a); 3) activators of the adenylate cyclase signaling pathway (e.g., dibutyryl cyclic AMP, theophylline); 4) cycloheximide; and 5) anti-cytoskeleton agents (e.g., cytochalasin B, colcemid). However, PMA and SF pathways were distinguishable: 1) PMA induced additional migration at saturating SF concentrations; 2) the onset of migration-stimulation was immediate for PMA and delayed for SF; and 3) down-modulation of protein kinase C (PKC) ablated PMA but not SF responsiveness. Assessment of PKC by (3H)-phorbol ester (PDBu) binding and by immunoblot showed 1) scatter factor does not cause significant redistribution or down-modulation of PDBu binding or alpha-PKC; and 2) PDBu mediates redistribution and down-modulation of both binding and alpha-PKC. These findings suggest two pathways for BBEC motility: a PKC-dependent pathway and an SF-stimulated/PKC-independent pathway.
Effect of Preexisting Immunity on Oncolytic Adenovirus Vector INGN 007 Antitumor Efficacy in Immunocompetent and Immunosuppressed Syrian Hamsters (2008)

Immune responses against adenovirus (Ad) vectors pose a possible concern for the outcome of treatment efficacy. To address the role of preexisting immunity in oncolytic Ad vector antitumor efficacy following intratumoral injection of vector as well as tumor-to-tissue spread of the vector, we employed the Syrian hamster model. These animals are immunocompetent, and their tumors and tissues are permissive for replication of Ad type 5 (Ad5). We used the adenovirus death protein-overexpressing Ad5-based vector INGN 007. Subcutaneous tumors were established in groups of hamsters that were or were not immunized with Ad5. Half of the hamsters in these groups were immunosuppressed with cyclophosphamide. For all groups, tumors injected with INGN 007 grew significantly more slowly than those injected with buffer. Under immunocompetent conditions, there was no significant effect of preexisting immunity on vector antitumor efficacy. Soon after the tumors in naïve animals were injected with vector, the hamsters developed neutralizing antibody (NAb) and the difference in NAb titers between the naïve and immunized groups diminished. Under immunosuppressed conditions, preexisting NAb did significantly reduce vector efficacy. Thus, NAb do reduce vector efficacy to some extent, but immunosuppression is required to observe the effect. Regarding vector toxicity, there was spillover of vector from the tumor to the liver and lungs in naïve immunocompetent hamsters, and this was nearly eliminated in the immunized hamsters. Thus, preexisting immunity to Ad5 does not affect INGN 007 antitumor efficacy following intratumoral injection, but immunity prevents vector spillover from the tumor to the liver and lungs.
TDP-43 Binds Heterogeneous Nuclear Ribonucleoprotein A/B through Its C-terminal Tail (2005)

TDP-43 is a highly conserved nuclear factor of yet unknown function that binds to ug-repeated sequences and is responsible for cystic fibrosis transmembrane conductance regulator exon 9 splicing inhibition. We have analyzed TDP-43 interactions with other splicing factors and identified the critical regions for the protein/protein recognition events that determine this biological function. We show here that the C-terminal region of TDP-43 is capable of binding directly to several proteins of the heterogeneous nuclear ribonucleoprotein (hnRNP) family with well known splicing inhibitory activity, in particular, hnRNP A2/B1 and hnRNP A1. Mutational analysis showed that TDP-43 proteins lacking the C-terminal region could not inhibit splicing probably because they were unable to form the hnRNP-rich complex involved in splicing inhibition. Finally, through splicing complex analysis, we show that splicing inhibition mediated by TDP-43 occurs at the earliest stages of spliceosomal assembly.
Susceptibility of Biofilms to Bdellovibrio bacteriovorus Attack (2005)

Biofilms are communities of microorganisms attached to a surface, and the growth of these surface attached communities is thought to provide microorganisms with protection against a range of biotic and abiotic agents. The capability of the gram-negative predatory bacterium Bdellovibrio bacteriovorus to control and reduce an existing Escherichia coli biofilm was evaluated in a static assay. A reduction in biofilm biomass was observed as early as 3 h after exposure to the predator, and an 87% reduction in crystal violet staining corresponding to a 4-log reduction in biofilm cell viability was seen after a 24-h exposure period. We observed that an initial titer of Bdellovibrio as low as 10(2) PFU/well or an exposure to the predator as short as 30 min is sufficient to reduce a preformed biofilm. The ability of B. bacteriovorus to reduce an existing biofilm was confirmed by scanning electron microscopy. The reduction in biofilm biomass obtained after the first 24 h of exposure to the predator remained unchanged even after longer exposure periods and reinoculation of the samples with fresh Bdellovibrio; however, no genetically stable resistant population of the host bacteria could be detected. Our data suggest that growth in a biofilm does not prevent predation by Bdellovibrio but allows a level of survival from attack greater than that observed for planktonic cells. In flow cell experiments B. bacteriovorus was able to decrease the biomass of both E. coli and Pseudomonas fluorescens biofilms as determined by phase-contrast and epifluorescence microscopy.
Activation of diverse eicosanoid pathways in osteoarthritic cartilage: a lipidomic and genomic analysis. (2012)

These studies for the first time demonstrate that normal and OA cartilage generates multiple and differential eicosanoid products. Inhibition of the COX- pathway in human OA cartilage caused accumulation of end products (LTB4) of the 5LO pathway. Furthermore, celecoxib, a selective COX-2 inhibitor, regulated numerous genes in cartilage, which are linked to the NFkB and AP-1 pathways at the mRNA level. In conclusion, these experiments demonstrate the complex and pleotropic role of eicosanoids in human cartilage homeostasis and pathophysiology of OA.
Moduli, Motives, Mirrors (2001)

This talk is dedicated to various aspects of Mirror Symmetry. It summarizes some of the mathematical developments that took place since M. Kontsevich’s report at the Zürich ICM and provides an extensive, although not exhaustive bibliography.
Highly Efficient “On Water” Catalyst‐Free Nucleophilic Addition Reactions Using Difluoroenoxysilanes: Dramatic Fluorine Effects (2014)

A remarkable fluorine effect on "on water" reactions is reported. The CF⋅⋅⋅HO interactions between suitably fluorinated nucleophiles and the hydrogen-bond network at the phase boundary of oil droplets enable the formation of a unique microstructure to facilitate on water catalyst-free reactions, which are difficult to realize using nonfluorinated substrates. Accordingly, a highly efficient on water, catalyst-free reaction of difluoroenoxysilanes with aldehydes, activated ketones, and isatylidene malononitriles was developed, thus leading to the highly efficient synthesis of a variety of α,α-difluoro-β-hydroxy ketones and quaternary oxindoles.
Characterization of a compressively sampled photonic link (2011)

A compressively sampled, photonic link has been described. By appropriately modulating the incoming signal prior to digitization, slow sampling rates can be used to accurately recover data as if it had been sampled at much higher rates. By performing the modulation in the optical domain there exists a potential path toward the recovery of signals in the 100GS/s regime.
Growth and immunogenicity of influenza viruses cultivated in Vero or MDCK cells and in embryonated chicken eggs. (1999)

Vero cells, MDCK cells and embryonated chicken eggs (eggs) were used to evaluate influenza virus growth characteristics and immunogenicity induced by inactivated influenza B vaccines. Both cell lines produced comparable quantities of total viral and haemagglutinin (HA) proteins. Sequence analysis indicated genetic identity of the HA of Vero- and MDCK-grown virus counterparts with maintenance of antigenic characteristics of viruses derived from humans. The egg-grown influenza B/Memphis/1/93 variant differed from cell-grown counterparts at amino acid position 198 (Pro-Thr) and lost a glycosylation site. The level of neuraminidase (NA) activity was the highest in egg-grown virus, while MDCK- and Vero cell-grown viruses possessed 70% and 90% less NA activity respectively when fetuin was used as a substrate. Although each of the vaccines induced high and comparable levels of serum antibodies, mammalian cell-derived vaccines induced antibodies that were more cross reactive, and those antibodies induced by egg-derived vaccine were more specific to the homologous antigen. ELISPOT analysis indicated that the mammalian cell-grown vaccines induced high frequencies of IgG-producing cells directed against both cell- and egg-grown antigens, while egg-grown vaccine induced high frequencies of IgG and IgM-producing cells reacting with homologous antigen and low levels of IgG-producing cells reactive with cell-grown virus antigen. Taken together, our results suggest that mammalian cells are a viable option for the production of influenza virus vaccines.
Synthesis of 3‐substituted 7‐(3,3‐dimethyl‐1‐triazeno)‐10‐methylphenothiazines as potential antitumor agents (1981)

Abstract A series of 3‐substituted (chloro, bromo, fluoro or methyl) 7‐(3,3‐dimethyl‐1‐triazeno)‐10‐methylphenothiazines were synthesized as potential antitumor agents. Treatment of p ‐substituted anilines with ammonium thiocyanate in the presence of bromine gave 6‐substituted 2‐aminobenzthiazoles which, after methylation with methyl iodide were hydrolyzed in 50% potassium hydroxide to give 5‐substituted 2‐methylaminothiophenols in moderate yield. Condensation of methylaminothiophenols with 3,4‐dichloronitrobenzene in ethanol under an atomsphere of nitrogen gave adducts which were cyclized in dimethylformamide under the catalysis of copper and cuprous iodide to give 3‐substituted 7‐nitro‐10‐methylphenothiazines. The nitro group was reduced to the amino function with stannous chloride. Diazotization of the amines followed by coupling with dimethylamine gave the corresponding triazenes.
Integration and characterization of micromachined optical microphones (2009)

The focus of this study is the optoelectronic integration of a micro-optical displacement detection architecture with a biomimetic MEMS microphone membrane based on the directional hearing mechanism of the parasitic fly Ormia Ochracea. The micromachined microphones feature optical interferometric displacement detection achieved using a commercially available Vertical Cavity Surface Emitting Laser (VCSEL) coupled with a custom designed silicon photodiode array. This design is shown to have significant advantages over conventional hearing aid microphones, which employ capacitive detection.&#13;\n&#13;\nA Multi-Chip Module (MCM) optoelectronic package is designed to integrate the biomimetic membrane with the optical displacement detection electronics in order to produce a fully integrated acoustic sensor. The modular package components, which are fabricated using high resolution stereolithography apparatus (SLA) equipment, provide accurate optical alignment of the optoelectronic components and allow complete device integration in a package with a total volume under 0.5cc. &#13;\n &#13;\nCharacterization of the integrated microphones is described in detail, including measurements of sensitivity, noise floor and directivity. A displacement resolution of 3.5x10⁻¹³ m/√Hz was measured between 4kHz and 16kHz in an anechoic test chamber, corresponding to a dynamic range of 115dB for the optical detection architecture. The total noise SPL of the device is 35.9dBA. Unlike capacitive microphones with similar noise levels, the device developed in this work exhibits first order dipole directivity patterns between 250Hz-1kHz, with an ideal Directivity Index of 4.8dB @ 1kHz and directional attenuation exceeding 25dB. With these results the optoelectronic package presented in this work demonstrates the viability of the integrated optical biomimetic microphones in compact, low power applications, specifically directional hearing aids.
Magnetic Resonance: An Introduction to Ultrashort TE (UTE) Imaging (2003)

The background underpinning the clinical use of ultrashort echo-time (UTE) pulse sequences for imaging tissues or tissue components with short T2s is reviewed. Tissues properties are discussed, and tissues are divided into those with a majority of short T2 relaxation components and those with a minority. Features of the basic physics relevant to UTE imaging are described including the fact that when the radiofrequency pulse duration is of the order T2, rotation of tissue magnetization into the transverse plane is incomplete. Consequences of the broad line-width of short T2 components are also discussed including their partial saturation by off-resonance fat suppression pulses as well as multislice and multiecho imaging. The need for rapid data acquisition of the order T2 is explained. The basic UTE pulse sequence with its half excitation pulse and radial imaging from the center of k-space is described together with options that suppress fat and/or long T2 components. Image interpretation is discussed. Clinical features of the imaging of cortical bone, tendons, ligaments, menisci, and periosteum as well as brain, liver, and spine are illustrated. Short T2 components in all of these tissues may show high signals. Possible future developments are outlined as are technical limitations.
The development of a qualitative assay for male infertility from a study of enzymes in human semen (1977)

Various enzymes in the semen of men were examined to see if any could be related to measures of fertility. Fumarase activity was highly correlated with sperm number and percentage motility. Diamine oxidase activity was higher in samples with sperm counts of less than 20 X 10(6)/ml and aperm motility of less than 20%. Monoamine oxidase, adenine deaminase and prostaglandin dehydrogenase were undetectable in significant amounts in all samples, while peroxidase and adenosine deaminase were not correlated with sperm count and motility. It is suggested that the simple spectrophotometric assays for fumarase and diamine oxidase could form the basis of a routine assessment of human semen samples for estimation of male infertility.
Microfluidic static droplet arrays with tuneable gradients in material composition (2011)

We describe a one-step passive strategy to create concentration gradients in static droplet arrays. The technique exploits controlled exchange of materials between moving plugs and stationary drops. The concentration of soluble reagents can be varied from drop-to-drop in the presence of other soluble reagents or insoluble materials (e.g. cells) at well-defined time points.
Concurrent VLSI Architectures (1984)

This tutorial paper addresses some of the principles and provides examples of concurrent architectures and designs that have been inspired by VLSI technology. The circuit density offered by VLSI provides the means for implementing systems with very large numbers of computing elements, while its physical characteristics provide an incentive to organize systems so that the elements are relatively loosely coupled. One class of computer architectures that evolve from this reasoning include an interesting and varied class of concurrent machines that adhere to a structural model based on the repetition of regularly connected elements. The systems included under this structural model range from 1) systems that combine storage and logic at a fine grain size, and are typically aimed at computations with images or storage retrieval, to 2) systems that combine registers and arithmetic at a medium grain size to form computational or systolic arrays for signal processing and matrix computations, to 3) arrays of instruction interpreting computers that use teamwork to perform many of the same demanding computations for which we use high-performance single process computers today.
Molecular cloning of a human UDP‐galactose:GlcNAcβ1,3GalNAc β1,3 galactosyltransferase gene encoding an O‐linked core3‐elongation enzyme (1999)

Using the full-length amino-acid sequences of the human beta1,3 galactosyltransferase (beta3GalT)-I, -II and III enzymes as query, we have identified an additional member of the beta3GalT gene family within a sequenced region of the human chromosome 21 as found in GenBank. The novel human beta3GalT-V gene included an open reading frame of 933 bp encoding a protein of 310 amino acids with a short N-terminal cytoplasmic tail, a single predicted transmembrane domain and a large lumenal catalytic domain. The human beta3GalT-V protein showed 34%, 27%, 31% and 23% sequence identity with the human beta3GalT-I, -II, -III and -IV enzymes, respectively. The expression of beta3GalT-V as a recombinant protein in Sf9 insect cells confirmed the galactosyltransferase activity catalyzed by this enzyme. Similarly to beta3GalT-I, -II and -III, the beta3GalT-V enzyme used beta-linked GlcNAc as an acceptor, but unlike the former enzymes beta3GalT-V exhibited a marked preference for the O-linked core3 GlcNAcbeta1,3GalNAc substrate. The beta3GalT-V gene was mainly expressed in human small intestine and to a lesser extent in pancreas and testis. Although beta3GalT-V transcripts were not detected in normal colon tissue, based on Northern analysis, beta3GalT-V mRNA was found in the adenocarcinoma cell line Colo 205.