gebhart/patrepeval huggingface dataset:
In Vitro Kinetic Studies of Formation of Antigenic Advanced Glycation End Products (AGEs) (1997)

Nonenzymatic protein glycation (Maillard reaction) leads to heterogeneous, toxic, and antigenic advanced glycation end products ("AGEs") and reactive precursors that have been implicated in the pathogenesis of diabetes, Alzheimer's disease, and normal aging. In vitro inhibition studies of AGE formation in the presence of high sugar concentrations are difficult to interpret, since AGE-forming intermediates may oxidatively arise from free sugar or from Schiff base condensation products with protein amino groups, rather than from just their classical Amadori rearrangement products. We recently succeeded in isolating an Amadori intermediate in the reaction of ribonuclease A (RNase) with ribose (Khalifah, R. G., Todd, P., Booth, A. A., Yang, S. X., Mott, J. D., and Hudson, B. G. (1996) Biochemistry 35, 4645-4654) for rapid studies of post-Amadori AGE formation in absence of free sugar or reversibly formed Schiff base precursors to Amadori products. This provides a new strategy for a better understanding of the mechanism of AGE inhibition by established inhibitors, such as aminoguanidine, and for searching for novel inhibitors specifically acting on post-Amadori pathways of AGE formation. Aminoguanidine shows little inhibition of post-Amadori AGE formation in RNase and bovine serum albumin, in contrast to its apparently effective inhibition of initial (although not late) stages of glycation in the presence of high concentrations of sugar. Of several derivatives of vitamins B1 and B6 recently studied for possible AGE inhibition in the presence of glucose (Booth, A. A., Khalifah, R. G., and Hudson, B. G. (1996) Biochem. Biophys. Res. Commun. 220, 113-119), pyridoxamine and, to a lesser extent, thiamine pyrophosphate proved to be novel and effective post-Amadori inhibitors that decrease the final levels of AGEs formed. Our mechanism-based approach to the study of AGE inhibition appears promising for the design and discovery of novel post-Amadori AGE inhibitors of therapeutic potential that may complement others, such as aminoguanidine, known to either prevent initial sugar attachment or to scavenge highly reactive dicarbonyl intermediates.
ECG signal coding methods in digital systems (2018)

Article contains an overview of ECG signal coding methods. The presented methods are used to record and present the raw ECG signal in digital systems. The aim of the presentation is to choose the best technique for use in the ECG recording device, currently being developed by the authors.
FK866, a highly specific noncompetitive inhibitor of nicotinamide phosphoribosyltransferase, represents a novel mechanism for induction of tumor cell apoptosis. (2003)

Deregulation of apoptosis, the physiological form of cell death, is closely associated with immunological diseases and cancer. Apoptosis is activated either by death receptor-driven or mitochondrial pathways, both of which may provide potential targets for novel anticancer drugs. Although several ligands stimulating death receptors have been described, the actual molecular events triggering the mitochondrial pathway are largely unknown. Here, we show initiation of apoptosis by gradual depletion of the intracellular coenzyme NAD+. We identified the first low molecular weight compound, designated FK866, which induces apoptosis by highly specific, noncompetitive inhibition of nicotinamide phosphoribosyltransferase (NAPRT), a key enzyme in the regulation of NAD+ biosynthesis from the natural precursor nicotinamide. Interference with this enzyme does not primarily intoxicate cells because the mitochondrial respiratory activity and the NAD+ -dependent redox reactions involved remain unaffected as long as NAD+ is not effectively depleted by catabolic reactions. Certain tissues, however, have a high turnover of NAD+ through its cleavage by enzymes like poly(ADP-ribose) polymerase. Such cells often rely on the more readily available nicotinamide pathway for NAD+ synthesis and undergo apoptosis after inhibition of NAPRT, whereas cells effectively using the nicotinic acid pathway for NAD+ synthesis remain unaffected. In support of this concept, FK866 effectively induced delayed cell death by apoptosis in HepG2 human liver carcinoma cells with an IC(50) of approximately 1 nM, did not directly inhibit mitochondrial respiratory activity, but caused gradual NAD+ depletion through specific inhibition of NAPRT. This enzyme, when partially purified from K562 human leukemia cells, was noncompetitively inhibited by FK866, and the inhibitor constants were calculated to be 0.4 nM for the enzyme/substrate complex (K(i)) and 0.3 nM for the free enzyme (K(i)'), respectively. Nicotinic acid and nicotinamide were both found to have antidote potential for the cellular effects of FK866. FK866 may be used for treatment of diseases implicating deregulated apoptosis such as cancer for immunosuppression or as a sensitizer for genotoxic agents. Furthermore, it may provide an important tool for investigation of the molecular triggers of the mitochondrial pathway leading to apoptosis through enabling temporal separation of NAD+ decrease from ATP breakdown and apoptosis by several days.
Frequency Synthesizer Design Handbook (1994)

Building Blocks for Frequency Synthesis Using Phase-Locked Loops. Phase Noise and Its Impact Upon System Performance. Phase-Locked Loop Analysis for Continuous Linear Systems. Frequency Synthesis Using Sampled-Data Control Systems. Fast-Switching Frequency Synthesizer Design Considerations. Hybrid Phase-Locked Loops. MACSET -- A Computer Program for the Design and Analysis of Phase-Locked Loop Frequency Synthesizers. Fractional-N Frequency Synthesis.
Mammalian and Yeast ras Gene Products: Biological Function in Their Heterologous Systems (1985)

Activated versions of ras genes have been found in various types of malignant tumors. The normal versions of these genes are found in organisms as diverse as mammals and yeasts. Yeast cells that lack their functional ras genes, RASSC-1 and RASSC-2, are ordinarily nonviable. They have now been shown to remain viable if they carry a mammalian rasH gene. In addition, yeast-mammalian hybrid genes and a deletion mutant yeast RASSC-1 gene were shown to induce morphologic transformation of mouse NIH 3T3 cells when the genes had a point mutation analogous to one that increases the transforming activity of mammalian ras genes. The results establish the functional relevance of the yeast system to the genetics and biochemistry of cellular transformation induced by mammalian ras genes.
Hepatic Stellate Cells: Unique Characteristics in Cell Biology and Phenotype (2003)

Hepatic stellate cells (HSCs), a mesenchymal cell type in hepatic parenchyma, have unique features with respect to their cellular origin, morphology, and function. Normal, quiescent HSCs function as major vitamin A-storing cells containing over 80% of total vitamin A in the body to maintain vitamin A homeostasis. HSCs are located between parenchymal cell plates and sinusoidal endothelial cells, and extend well-developed, long processes surrounding sinusoids in vivo as pericytes. However, HSCs are known to be 'activated' or 'transdifferentiated' to myofibroblast-like phenotype lacking cytoplasmic lipid droplets and long processes in pathological conditions such as liver fibrosis and cirrhosis, as well as merely during cell culture after isolation. HSCs are the predominant cell type producing extracellular matrix (ECM) components as well as ECM degrading metalloproteases in hepatic parenchyma, indicating that they play a pivotal role in ECM remodeling in both normal and pathological conditions. Recent findings have suggested that HSCs have a neural crest origin from their gene expression pattern similar to neural cell type and/or smooth muscle cells and myofibroblasts. The morphology and function of HSCs are regulated by ECM components as well as by cytokines and growth factors in vivo and in vitro. Liver regeneration after partial hepatectomy might be an invaluable model to clarify the HSC function in elaborate organization of liver tissue by cell-cell and cell-ECM interaction and by growth factor and cytokine regulation.
Hall Effect in the Accumulation Layers on the Surface of Organic Semiconductors (2005)

We have observed the Hall effect in the field-induced accumulation layer on the surface of single-crystal samples of a small-molecule organic semiconductor rubrene. The Hall mobility muH increases with decreasing temperature in both the intrinsic (high-temperature) and trap-dominated (low-temperature) conduction regimes. In the intrinsic regime, the density of mobile field-induced charge carriers extracted from the Hall measurements, nH, coincides with the density n calculated using the gate-channel capacitance and becomes smaller than n in the trap-dominated regime. The Hall data are consistent with the diffusive bandlike motion of field-induced charge carriers between trapping events.
Group III Metabotropic Glutamate Receptor-Mediated Modulation of the Striatopallidal Synapse (2003)

The globus pallidus (GP) is a key GABAergic nucleus in the basal ganglia (BG). The predominant input to the GP is an inhibitory striatal projection that forms the first synapse in the indirect pathway. The GP GABAergic neurons project to the subthalamic nucleus, providing an inhibitory control of these glutamatergic cells. Given its place within the BG circuit, it is not surprising that alterations in GP firing pattern are postulated to play a role in both normal and pathological motor behavior. Because the inhibitory striatal input to the GP may play an important role in shaping these firing patterns, we set out to determine the role that the group III metabotropic glutamate receptors (GluRs) play in modulating transmission at the striatopallidal synapse. In rat midbrain slices, electrical stimulation of the striatum evoked GABA(A)-mediated IPSCs recorded in all three types of GP neurons. The group III mGluR-selective agonist L-(+)-2-amino-4-phosphonobutyric acid (L-AP4) inhibited these IPSCs through a presynaptic mechanism of action. L-AP4 exhibited high potency and a pharmacological profile consistent with mediation by mGluR4. Furthermore, the effect of L-AP4 on striatopallidal transmission was absent in mGluR4 knock-out mice, providing convincing evidence that mGluR4 mediates this effect. The finding that mGluR4 may selectively modulate striatopallidal transmission raises the interesting possibility that activation of mGluR4 could decrease the excessive inhibition of the GP that has been postulated to occur in Parkinson's disease. Consistent with this, we find that intracerebroventricular injections of L-AP4 produce therapeutic benefit in both acute and chronic rodent models of Parkinson's disease.
Ground Penetrating Radar Theory, Data Collection, Processing, and Interpretation: A Guide for Archaeologists (2012)

This guide was originally written as a term project for a Graduate Research Seminar (Anthropology 545) directed by Dr. Andrew Martindale at the University of British Columbia in 2010-11. It was produced as a teaching tool for students in the Department of Anthropology and other users of the Laboratory of Archaeology’s ground penetrating radar (GPR) equipment. The guide provides a review of GPR theory, data collection, processing, and interpretation, presented in three sections. Section 1 (GPR Fundamentals) focuses on the principles of GPR: how electromagnetic radar waves move through the ground, what happens when they encounter subsurface features, and how they are imaged in GPR software programs. Section 2 (Data Editing and Processing) focuses specifically on what happens to the data after collection in the field, when they are returned to the lab and undergo a variety of processes to transform them into two- and three-dimensional images of the subsurface. Section 3 (Data Interpretation) focuses on how we read these computer-generated images, and provides descriptions of the various signal types that can be produced from common archaeological features. A companion guide focusing on GPR data collection is forthcoming by Steve Daniel.
Miniature, High-Power 355-nm Laser System (2003)

A robust, miniature laser system produces &gt;100 µJ in 355-nm pulses of 700-ps duration, at pulse rates up to 500 Hz. The system is pumped by two fiber-coupled 808-nm diode-laser arrays and occupies a volume of &lt;0.5 liters.
Regioselective Lewis Acid-Mediated [1,3] Rearrangement of Allylvinyl Ethers (2005)

[reaction: see text]. Aluminum and copper Lewis acids were implemented to effect a regioselective [1,3] rearrangement of allylvinyl ethers in moderate to good yields. The use of trisubstituted alkenes leads to depressed levels of Claisen products.
Efficient exact arithmetic for computational geometry (1993)

We experiment with exact integer arithmetic to implement primitives for geometric algorithms. Naive use of exact arithmetic—either modular or multiprecision integer—increases execution time dramatically over the use of floating-point arithmetic. By combining tuned multiprecision integer arithmetic and a floating-point filter based on interval analysis, we can obtain the effect of exact integer arithmetic at a cost close to that of floating-point arithmetic. We describe an experimental expression compiler that conveniently packages our techniques.
The treatment of rosacea. (2004)

The roundtable discussion encompassed many topics-from seminal research by Ronald Marks to the latest National Rosacea Society-funded studies on the pathophysiology of rosacea. All participants commented on the value of the new National Rosacea Society classification system for subtypes of rosacea, designed to direct future research and help physicians better diagnose and manage these subtypes. A lively discussion centered on treatment options for the various subtypes of rosacea ensued.
Micelles and Microemulsions (1992)

Machine learning (ML) is transforming all areas of science. The complex and time-consuming calculations in molecular simulations are particularly suitable for an ML revolution and have already been profoundly affected by the application of existing ML ...Read More
Replication control genes of plasmid pE194 (1987)

pE194, a 3.7-kilobase plasmid, confers resistance to macrolide, lincosamide, and streptogramin B antibiotics. The previously identified cop and repF genes of pE194 have been further localized by molecular cloning and mutational analysis together with DNA sequencing. The CfoIB fragment of pE194 is capable of autonomous replication and contains both genes. Most of this region has been resequenced, and two errors reported in a previous study have been corrected. The corrected sequence indicates that the replication region contains a single large open reading frame, which we propose encodes the repF product. Northern blot (RNA blot) analysis of this region detected six transcripts, all transcribed in the same direction as one another and opposite to repF. A 350-base transcript is synthesized from the region containing cop. No in vivo transcript for the repF gene was detected, but a protein was observed in an in vitro transcription-translation system which appears to be its product. An ochre mutation was inserted in the putative repF open reading frame, and a nonsense fragment was detected in the in vitro system. When carried passively on a pUB110 replicon, this mutant product appears capable of inhibiting pE194 replicons in trans. The pE194 origin of replication has been localized to within 200 bases.
Isoniazid prevents Nrf2 translocation by inhibiting ERK1 phosphorylation and induces oxidative stress and apoptosis (2015)

Isoniazid is used either alone or in combination with other drugs for the treatment of tuberculosis. It is also used for the prevention of tuberculosis. Chronic treatment of Isoniazid may cause severe liver damage leading to acute liver failure. The mechanism through which Isoniazid causes liver damage is investigated. Isoniazid treatment generates reactive oxygen species and induces apoptosis in Hep3B cells. It induces antioxidative and apoptotic genes leading to increase in mRNA expression and protein levels in Hep3B cells. Whole genome expression analysis of Hep3B cells treated with Isoniazid has resulted in differential expression of various genes playing prime role in regulation of apoptotic, antioxidative, DNA damage, cell signaling, cell proliferation and differentiation pathways. Isoniazid increased cytosolic Nrf2 protein level while decreased nuclear Nrf2 protein level. It also decreased ERK1 phosphorylation and treatment of Hep3B cells with ERK inhibitor followed by Isoniazid resulting in increased apoptosis in these cells. Two dimensional gel electrophoresis results have also shown differential expression of various protein species including heat shock proteins, proteins playing important role in oxidative stress, DNA damage, apoptosis, cell proliferation and differentiation. Results suggest that Isoniazid induces apoptosis through oxidative stress and also prevents Nrf2 translocation into the nucleus by reducing ERK1 phosphorylation thus preventing cytoprotective effect.
Efficient method for construction comprehensive murine Fab antibody libraries displayed on phage (1993)

We have developed efficient methodologies for construction and expression of comprehensive phage display libraries of murine Fab antibody fragments in E. coli cells. Our methods optimize several critical steps of the polymerase chain reaction (PCR) amplification of transcripts of the re-arranged immunoglobulin genes and of their subsequent assembly and expression: Firstly, we have designed exhaustive sets of PCR primers of low degeneracy for the amplification of transcripts of the Fab region of the heavy and light-chain genes. These primers proved effective in amplification of Fab gene fragments from a large panel of hybridoma cell lines of different specificity and family sub-type. Secondly, we have developed a 'jumping PCR' technique that effectively assembled and recombined the amplified heavy and light-chain gene fragments into a bi-cistronic operon. Thirdly, we have constructed expression vectors for insertion of the combinatorial Fab gene-cassette in fusion with a truncated version of the phage surface protein, gIIIp. The heavy chain and the light chain-gIII fusion are transcribed as a polycistronic mRNA from the lacZ promoter and efficient transcriptional control is provided by wildtype lacI present on the vector. The utility of the system was demonstrated by isolating several antigen-binding clones from hybridomas and libraries made from immunized mice.
Rapid preparation of DNA from filamentous fungi (1985)

We describe a general, simple and inexpensive method for the isolation of DNA from filamentous fungi. Starting from freeze-dried mycelium 01–015% by weight can be isolated as high molecular weight DNA suitable for restriction and ligation in 2 h. The preparation can be done in Eppendorf tubes and allows the processing of many samples in parallel. We have used the method with the basidiomycetes Phanerochaete chrysosporium, Coprinus cinereus and the ascomycete Aspergillus nidulans and others have used it with Trichoderma reesei, Aspergillus niger and for the isolation of DNA from tomato plants.
Are All Chimeric Antigen Receptors Created Equal? (2015)

Article Tools UNDERSTANDING THE PATHWAY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2014.57.5472 Journal of Clinical Oncology - published online before print January 20, 2015 PMID: 25605860 Are All Chimeric Antigen Receptors Created Equal? Jae H. ParkxJae H. ParkSearch for articles by this author , Renier J. BrentjensxRenier J. BrentjensSearch for articles by this author Show More Memorial Sloan Kettering Cancer Center, New York, NY https://doi.org/10.1200/JCO.2014.57.5472 First Page Full Text PDF Figures and Tables © 2015 by American Society of Clinical Oncology
Human-machine interfaces (2015)

Abstract : The normal human auditory system suffers from many deficiencies in its ability to localize sound sources in space. Not only is it generally poor at determining the elevation and distance of a sound source, but in certain cases it is relatively poor at determining the azimuth of the source. The research discussed in this report is concerned with the development and evaluation of systems that result in improved localization, i.e., in supernormal auditory localization, by altering the localization cues that are available to the listener. Although such enhanced performance should be of value in essentially all systems that make use of auditory localization for conveying information to the human user, the application area of primary interest in this proposal is that of human-machine interfaces for teleoperator and virtual systems. In general, localization performance can be summarized in terms of (1) resolution and (2) response bias. Resolution refers to the ability to detect small changes in the spatial position of a sound source and to separate out multiple sources located at different positions, as well as to the amount of information transfer that can be achieved in the identification of source position. Response bias refers to the average differences between perceived source position (as measured by the mean of the listener's objective responses) and the actual source position.
Stencil mask ion implantation technology for sub 100 nm technology node (2002)

Recently we develop Stencil Mask ion Implantation Technology (SMIT). Using SMIT, the cost of fabricating semiconductor devices can be reduced. In view of the ion beam profile and system configuration, the SMIT system is advantageous in term of device performance. We propose SMIT and show some fundamental results of SMIT in this report.
Possible involvement of leptospires in abortion, stillbirths and neonatal deaths in sheep (1983)

Using culture, immunofluorescence and fetal serology, leptospiral infection was demonstrated in aborted, stillborn and weak lambs from nine out of 42 flocks investigated during the 1980 and 1981 lambing seasons. Three serogroups of leptospira, namely the Hebdomadis, Australis and Pomona serogroups, were implicated.
Domain organization of the adenovirus preterminal protein (1997)

In adenovirus-infected cells, the virus-encoded preterminal protein and DNA polymerase form a heterodimer that is directly involved in initiation of DNA replication. Monoclonal antibodies were raised against preterminal protein, and epitopes recognized by the antibodies were identified by using synthetic peptides. Partial proteolysis of preterminal protein reveals that it has a tripartite structure, with the three domains being separated by two protease-sensitive areas, located at sites processed by adenovirus protease. These areas of protease sensitivity are probably surface-exposed loops, as they are the sites, along with the C-terminal region of preterminal protein, recognized by the monoclonal antibodies. Preterminal protein is protected from proteolytic cleavage when bound to adenovirus DNA polymerase, suggesting either multiple contact points between the proteins or a DNA polymerase-induced conformational change in preterminal protein. Two of the preterminal protein-specific antibodies induced dissociation of the preterminal protein-adenovirus DNA polymerase heterodimer and inhibited initiation of adenovirus DNA replication in vitro. Antibodies binding close to the primary processing sites of adenovirus protease inhibited DNA binding, consistent with UV cross-linking results which reveal that an N-terminal, protease-resistant domain of preterminal protein contacts DNA. Monoclonal antibodies recognizing epitopes within the C-terminal 60 amino acids of preterminal protein stimulate DNA binding, an effect mediated through a decrease in the dissociation rate constant. These results suggest that preterminal protein contains a large, noncontiguous surface required for interaction with DNA polymerase, an N-terminal DNA binding domain, and a C-terminal regulatory domain.