gebhart/patrepeval huggingface dataset:
The glutathione-binding site in glutathione S-transferases. Investigation of the cysteinyl, glycyl and γ-glutamyl domains (1990)

The GSH-binding site of glutathione S-transferase (GST) isoenzymes was studied by investigating their substrate-specificity for three series of GSH analogues; further, a model of the interactions of GSH with the G-site is proposed. Twelve glycyl-modified GSH analogues, four ester derivatives of GSH and three cysteinyl-modified GSH analogues were synthesized and tested with purified forms of rat liver GST (1-1, 2-2, 3-3 and 4-4). The glycyl analogues exhibited spontaneous chemical reaction rates with 1-chloro-2,4-dinitrobenzene comparable with the GSH rate. In contrast, the enzymic rates (Vmax.) differed greatly, from less than 1 up to 140 mumol/min per mg; apparently, a reaction mechanism is followed that is very sensitive to substitutions at the glycyl domain. No correlation exists between the chemical rates and Vmax. values for the analogues. Analogues of GSH in which L-cysteine was replaced by D-cysteine, L-homocysteine or L-penicillamine showed little or no capacity to replace GSH as co-substrate for the GSTs. GSH monomethyl and monoethyl esters showed Vmax. values greater than the Vmax. measured with GSH: the Vmax. for the monoethyl ester of GSH and GST 3-3 was 5-fold that for GSH. The data obtained in this and previous studies [Adang, Brussee, Meyer, Coles, Ketterer, van der Gen & Mulder (1988) Biochem. J. 255, 721-724; Adang, Meyer, Brussee, van der Gen, Ketterer & Mulder (1989) Biochem. J. 264, 759-764] allow a model of the interactions of GSH in the G-site in GSTs to be postulated. The gamma-glutamyl site is the main binding determinant: the alpha-carboxylate group is obligatory, whereas shifting of the amino group and shortening of the peptide backbone only decreased kcat./Km. Furthermore, the GSTs appear to be very critical with respect to a correct orientation of the thiol group of the GSH analogue. The glycyl site is the least restrictive domain in the G-site of GSTs: amino acid analogues all showed Km values between 0.2 and 0.6 mM (that for GSH is 0.2-0.3 mM), but large differences in Vmax. exist. The glycyl carboxylate group is not essential for substrate recognition, since decarboxy analogues and ester derivatives showed high activities. The possible mechanisms for an increased Vmax. in some analogues are briefly discussed.
Therapeutic applications of electromagnetic power (1974)

The use of electromagnetic (EM) power for therapeutic applications has existed since EM sources have been available to man. Physical medicine has been a major user of both shortwave (27.33 MHz) and microwave (2450 MHz) diathermy over the decades in which the EM power has been used to heat deep tissues for stimulating various medically beneficial physiologic responses in the relief of certain pathological conditions. Experimental and clinical research indicates that these responses will occur as a result of elevating the tissue temperatures in the range 41° to 45°C requiring absorbed power densities from 50 to 170 W/kg in the deep tissues where treatment is desired. The combination of pain responses and a large reserve of blood cooling capacity seems to be sufficient for limiting the heating to safe, but therapeutic levels in vasculated and innervated tissue. Recent research has shown that the use of the industrial, scientific, and medical (ISM) frequency of 915 MHz is more efficient than the currently used 2450-MHz microwave frequency in terms of maximum power transfer to deep tissues. The results also show that in addition to thermal applications, microwave energy can be used for the controlled transcutaneous stimulation of nerve action potentials via implanted miniature microwave diodes.
Translocation of Single-Stranded DNA Through Single-Walled Carbon Nanotubes (2009)

We report the fabrication of devices in which one single-walled carbon nanotube spans a barrier between two fluid reservoirs, enabling direct electrical measurement of ion transport through the tube. A fraction of the tubes pass anomalously high ionic currents. Electrophoretic transport of small single-stranded DNA oligomers through these tubes is marked by large transient increases in ion current and was confirmed by polymerase chain reaction analysis. Each current pulse contains about 10(7) charges, an enormous amplification of the translocated charge. Carbon nanotubes simplify the construction of nanopores, permit new types of electrical measurements, and may open avenues for control of DNA translocation.
Identification of potent nontoxic poly(ADP-Ribose) polymerase-1 inhibitors: chemopotentiation and pharmacological studies. (2003)

The nuclear enzyme poly(ADP-ribose) polymerase (PARP-1) facilitates DNA repair, and is, therefore, an attractive target for anticancer chemo- and radio-potentiation. Novel benzimidazole-4-carboxamides (BZ1-6) and tricyclic lactam indoles (TI1-5) with PARP-1 K(i) values of <10 nM have been identified. Whole cell PARP-1 inhibition, intrinsic cell growth inhibition, and chemopotentiation of the cytotoxic agents temozolomide (TM) and topotecan (TP) were evaluated in LoVo human colon carcinoma cells. The acute toxicity of the inhibitors was investigated in PARP-1 null and wild-type mice. Tissue distribution and in vivo chemopotentiation activity was determined in nude mice bearing LoVo xenografts. At a nontoxic concentration (0.4 micro M) the PARP-1 inhibitors potentiated TM-induced growth inhibition 1.0-5.3-fold and TP-induced inhibition from 1.0-2.1-fold. Concentrations of the PARP-1 inhibitors that alone inhibited cell growth by 50% ranged from 8 to 94 micro M. Maximum potentiation of TM activity was achieved at nongrowth inhibitory concentrations (</=1 micro M) of potent PARP-1 inhibitors BZ5 and TI4. Whole cell PARP-1 inhibition by BZ3, BZ5, BZ6, TI1, and TI4 was confirmed by attenuation of DNA damage-induced NAD(+) depletion. Selected inhibitors (TI1, TI3, and TI4), in contrast to the benchmark compound PD128763, caused only mild hypothermia in both PARP-1 null and wild-type mice. Excellent distribution of BZ5, TI1, and TI3 into tumor tissue was observed, and TI3 enhanced TM antitumor activity in vivo. These studies have identified potent nontoxic PARP-1 inhibitors with structural modifications that promote aqueous solubility, tolerability, and tissue distribution. These compounds are important leads in the development of clinically viable PARP-1 inhibitors.
Endothelial Apoptosis as the Primary Lesion Initiating Intestinal Radiation Damage in Mice (2001)

Gastrointestinal (GI) tract damage by chemotherapy or radiation limits their efficacy in cancer treatment. Radiation has been postulated to target epithelial stem cells within the crypts of Lieberkühn to initiate the lethal GI syndrome. Here, we show in mouse models that microvascular endothelial apoptosis is the primary lesion leading to stem cell dysfunction. Radiation-induced crypt damage, organ failure, and death from the GI syndrome were prevented when endothelial apoptosis was inhibited pharmacologically by intravenous basic fibroblast growth factor (bFGF) or genetically by deletion of the acid sphingomyelinase gene. Endothelial, but not crypt, cells express FGF receptor transcripts, suggesting that the endothelial lesion occurs before crypt stem cell damage in the evolution of the GI syndrome. This study provides a basis for new approaches to prevent radiation damage to the bowel.
Radiofrequency neurolysis in a clinical model (1981)

Reports differ on which nerve fibers are affected by radiofrequency lesions made in peripheral nerves, some stating that primarily the myelinated delta and unmyelinated C fibers are destroyed, others stating that the destruction affects all sizes of nerve fibers and both myelinated and unmyelinated fibers. This study was designed to confirm one of those two findings, and to study the role that different temperatures might play in determining which fibers are affected. Radiofrequency lesions (85 degrees C for 2 minutes) were made in dogs by placing a temperature-monitored electrode into the lumber intervertebral foramina. The dogs were killed at intervals up to 6 weeks after rhizotomy, and the lesions were studied by light and electron microscopy. In all lesions, there was a total loss of unmyelinated fibers and a nearly total loss of myelinated fibers. In other dogs, 2-minute lesions were made at 45 degrees, 55 degrees, 65 degrees, and 75 degrees C, and the lesions examined 1 week later. Again, all sizes and all types of fibers were destroyed.
Novel Recurrent Genetic Imbalances in Human Hepatocellular Carcinoma Cell Lines Identified by Comparative Genomic Hybridization (1999)

To search for recurrent and specific genomic alterations in human hepatocellular carcinoma (HCC), we examined 18 cell lines by comparative genomic hybridization (CGH), a molecular cytogenetic approach that allows positional identification of gains and losses of DNA sequences of the entire tumor genome. We report here a distinct pattern of multiple recurrent DNA copy-number gains and losses that include alterations frequently seen in other neoplasias as well as changes potentially specific for HCC. The most frequent gains were localized on 1p34.3-35, 1p33-34.1, 1q21-23, 1q31-32, 6p11-12, 7p21, 7q11.2, 8q24.1-24.2, 11q11-13, 12q11-13, 12q23, 17q11. 2-21, 17q23-24, and 20p11.1-q13.2. Recurrent losses were mapped on 3p12-14, 3q25, 4p12-14, 4q13-34, 5q21, 6q25-26, 8p11.2-23, 9p12-24, 11q23-24, 13q12-33, 14q12-13, 15q25-26, 18q11.2-22.2, and 21q21-22. Seventeen genomic imbalances are novel in HCC, thus extending significantly the map of genetic changes and providing a starting point for the isolation of new genes relevant in pathogenesis of liver neoplasia, as well as providing molecular probes for both diagnosis and monitoring treatment of the disease.
A Parallel Study of mRNA and microRNA Profiling of Peripheral Blood in Young Adult Women (2011)

Our results suggest that the change in global microRNA expression in the peripheral blood is associated with normal aging in young adult women. This change may precede global gene expression changes. Future studies are needed to investigate the regulatory mechanism of the estrogen-related microRNAs and associated diseases.
Antibodies to Capsular Polysaccharide and Clumping Factor A Prevent Mastitis and the Emergence of Unencapsulated and Small-Colony Variants ofStaphylococcus aureusin Mice (2008)

The pathogenesis of Staphylococcus aureus infections is influenced by multiple virulence factors that are expressed under variable conditions, and this has complicated the design of an effective vaccine. Clinical trials that targeted the capsule or clumping factor A (ClfA) failed to protect the recipients against staphylococcal infections. We passively immunized lactating mice with rabbit antibodies to S. aureus capsular polysaccharide (CP) serotype 5 (CP5) or CP8 or with monoclonal antibodies to ClfA. Mice immunized with antibodies to CP5 or CP8 or with ClfA had significantly reduced tissue bacterial burdens 4 days after intramammary challenge with encapsulated S. aureus strains. After several passages in mice passively immunized with CP-specific antiserum, increasing numbers of stable unencapsulated variants of S. aureus were cultured from the infected mammary glands. Greater numbers of these unencapsulated S. aureus variants than of the corresponding encapsulated parental strains were internalized in vitro in MAC-T bovine cells. Furthermore, small-colony variants (SCVs) were recovered from the infected mammary glands after several passages in mice passively immunized with CP-specific antiserum. A combination of antibodies effectively sterilized mammary glands in a significant number of passively immunized mice. More importantly, passive immunization with antibodies to both CP and ClfA fully inhibited the emergence of unencapsulated "escape mutants" and significantly reduced the appearance of SCVs. A vaccine formulation comprising CP conjugates plus a surface-associated protein adhesin may be more effective than either antigen alone for prevention of S. aureus infections.
High power density electric drive for an hybrid electric vehicle (2002)

This paper describes the electric drive system for an experimental hybrid electric vehicle 'Freedom'. The drive system is based on 4, PWM-VSI fed in-wheel PM brushless motors, using a novel PWM control strategy and a digital current phase angle control scheme that does not require a high resolution absolute position sensor. Each wheel of the vehicle is fitted with a 12-pole, 3-/spl phi/, PM motor with surface mounted Magnaquench magnets and an integral speed reducer packaged within the hollow rotor. Each PM motor is rated at 9 kW continuous (@3560 rpm) and 29 kW peak. The PM brushless motors had a trapezoidal EMF and were supplied with 120/spl deg/ quasi-square wave currents from the IGBT inverters operating at 18 kHz PWM frequency. The paper focuses on the development of the PWM-VSI inverters, the PWM strategy and the microcontroller system that implements the phase angle control scheme. Test results were provided on the performance of the electric drive. A new control strategy is outlined for controlling the braking torque when the battery is fully charged or when the motor speed exceeds the no-load speed. Two types of high power density inverter packages were developed for the Freedom vehicle. The Phase I system utilized forced air cooling to provide 32 kW peak power per inverter (@160 A pk) and Phase II system utilized direct liquid cooling to provide 45 kW peak power per inverter (@300 A pk). The liquid cooled system achieved an improvement of 2.5 times power density by weight and 4 times the power density by volume over the air cooled system.
Lymphoid reconstitution of the human fetal thymus in SCID mice with CD34+ precursor cells. (1991)

The search for human hematopoietic stem cells has been hampered by the lack of appropriate assay systems. Demonstration of the ability of precursor cell candidates to give rise to T cells is of significant difficulty since dissociated in vitro cultured thymus stroma cells lose their ability to sustain thymocyte maturation. To define further the differentiative capacities of the rare human fetal liver and bone marrow cells that express the CD34 surface antigen and exhibit in vitro myeloid and pre-B cell activities, we have microinjected them into HLA-mismatched fetal thymus fragments, partially depleted of hematopoietic cells by low temperature culture. In vitro colonized thymuses have then been allowed to develop upon engraftment into immunodeficient SCID mice. Using this modification of the SCID-hu system, we show that low numbers of fetal CD34+ progenitor cells can repopulate the lymphoid compartment in the human thymus.
A Hypnotic Response to Dexmedetomidine, an α2 Agonist, Is Mediated in the Locus Coerüleus in Rats (1992)

Dexmedetomidine, the highly selective alpha 2-adrenergic agonist, produces a dose-dependent hypnotic response in rats through a central mechanism. Because the locus coeruleus (LC) contains pathways involved in the maintenance of vigilance and a high prevalence of alpha 2 adrenoceptors, we investigated the role of this brainstem nucleus in the hypnotic response to dexmedetomidine. The experimental model consisted of chronic, stereotactically cannulated rats (n = 157) in which the hypnotic response to dexmedetomidine was assessed by the duration of the loss of their righting reflex. Correct placement of the cannula was confirmed histologically at necropsy. The hypnotic response to dexmedetomidine 0.3-333.3 micrograms administered into the LC increased in a dose-dependent fashion. Dexmedetomidine 6.6 micrograms injected 2 mm lateral to the LC did not cause the animals to lose their righting response. Atipamezole 0.07 micrograms-12 micrograms, a selective alpha 2-adrenergic antagonist, blocked the hypnotic response to dexmedetomidine 6.6 micrograms when both were administered into the LC. Also, atipamezole 0.7-30 micrograms, administered into the LC, blocked in a dose-dependent manner the hypnotic response to intraperitoneal (ip) dexmedetomidine 50 micrograms.kg-1. Atipamezole injected into the LC did not block the hypnotic response to pentobarbital 40 mg.kg-1 ip. Prazosin, an alpha 1-adrenergic antagonist, 4.2 micrograms into the LC or 1.0 mg.kg-1 ip, did not alter the hypnotic response to dexmedetomidine 6.6 micrograms into the LC. The present data suggest that alpha 2-adrenergic receptors in the LC appear to be a major site for the hypnotic action of dexmedetomidine.(ABSTRACT TRUNCATED AT 250 WORDS)
Security analysis of integrated circuit camouflaging (2013)

Camouflaging is a layout-level technique that hampers an attacker from reverse engineering by introducing, in one embodiment, dummy contacts into the layout. By using a mix of real and dummy contacts, one can camouflage a standard cell whose functionality can be one of many. If an attacker cannot resolve the functionality of a camouflaged gate, he/she will extract an incorrect netlist. In this paper, we analyze the feasibility of identifying the functionality of camouflaged gates. We also propose techniques to make the dummy contact-based IC camouflaging technique resilient to reverse engineering. Furthermore, we judiciously select gates to camouflage by using techniques which ensure that the outputs of the extracted netlist are controllably corrupted. The techniques leverage IC testing principles such as justification and sensitization. The proposed techniques are evaluated using ISCAS benchmark circuits and OpenSparc T1 microprocessor controllers.
Detection of drug resistance in human tumors by in vitro enzymatic amplification. (1988)

Both acquired and natural resistance to chemotherapy agents have proved problematic in the treatment of neoplasia. Thymidylate synthase, which catalyzes the synthesis of thymidine precursors, has been shown to be amplified in response to a variety of chemotherapeutic agents. The detection of such amplification could prove beneficial in the development of alternative clinical protocols. In this study we report the use of existing enzymatic amplification methods in order to detect incipient amplification of the thymidylate synthase gene upon resistance to cisplatin. The assay utilizes a modification of the polymerase chain reaction in which a sequence of the thymidylate synthase gene is amplified including two flanking oligonucleotides acting as primers for DNA synthesis. This method exhibits greater sensitivity than conventional nucleic acid detection methods and requires less than 100 ng of total RNA from patient tumors and no in vitro culturing of patient cells.
Fabrication of Silicon Carriers With TSV Electrical Interconnections and Embedded Thermal Solutions for High Power 3-D Packages (2009)

This paper presents micro fabrication process and wafer-level integration of a silicon carrier, which consists of two Si chips that are bonded together with evaporated AuSn-solder. There are micro fins and channels fabricated in the Si chip and form the embedded cooling layer after bonding. The embedded cooling layer is connected with an inlet and an outlet to form a fluidic path for heat transfer enhancement. Besides, in the silicon carrier, there are through silicon vias (TSVs) with metal film on sidewall for electrical interconnection. Two or more carriers can then be stacked together with a silicon interposer in between to make up of a stacked cooling module for high power heat dissipation. The advantage of this 3-D stacking method is that it provides a method of simultaneously realizing electrical interconnection and fluidic path and it can extract heat from the constraints of 3-D silicon module chips to surface without external liquid circulation.
White‐Light‐Emitting Diodes with Quantum Dot Color Converters for Display Backlights (2010)

Highly luminescent, multiply passivated green- and red-light-emitting quantum dots are used as color converters in InGaN blue LEDs to achieve external quantum efficiencies of 72% and 34%, respectively. White QD-LEDs prepared for a display backlight are shown to have an efficacy of 41 lm W−1 and color reproducibility of 100% compared to the NTSC standard in CIE 1931. Finally, a 46 inch LCD TV panel (see image) using the QD-LED backlight is successfully demonstrated for the first time. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Leukocyte Trafficking Mediated by Selectin-Carbohydrate Interactions (1995)

The selectins have attracted intense interest because of their carbohydrate-recognition properties and their pivotal roles in leukocyte trafficking. Future studies will center on the mechanisms for regulating the expression of the selectins and their ligands, the molecular details of selectin binding to glycoprotein ligands and small carbohydrates, and the biophysical principles that selectins employ to mediate attachment and rolling of leukocytes under flow.
Conservation, Surface Exposure, and In Vivo Expression of the Frp Family of Iron-Regulated Cell Wall Proteins in Staphylococcus aureus (2002)

Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis identified two conserved, immunogenic Staphylococcus aureus cell wall proteins, of 40 and 87 kDa, expressed under iron-restricted growth conditions in vitro and in vivo. N-terminal sequencing and subsequent genome analysis showed that these proteins are encoded by adjacent monocistronic open reading frames designated frpA and frpB, respectively. Studies with an S. aureus fur mutant confirmed that expression of FrpA and FrpB is regulated by Fur but that there also appears to be differential expression of these proteins in different iron-restricted media in vitro. FrpA and FrpB share some amino acid sequence homology with each other and with a putative S. aureus membrane protein, FrpC. frpC is the first gene of a Fur-regulated operon encoding four proteins of unknown function (FrpC, -D, -G, and -H) and the binding protein (FrpE) and permease (FrpF) of a putative iron transporter. Antisense mutagenesis and bioassays showed that FrpA and FrpB are not required for growth of S. aureus under iron-restricted conditions in vitro and do not appear to be involved in the transport of iron from siderophores or in binding of hemin. Further phenotypic analysis suggested that FrpA may be involved in adhesion of S. aureus to plastic in vitro. Binding of S. aureus to microtiter wells was found to be iron regulated, and iron-restricted S. aureus containing antisense frpA or frpAB but not frpB constructs showed reduced binding compared to vector construct controls.
Eculizumab for Congenital Atypical Hemolytic–Uremic Syndrome (2009)

To the Editor: Atypical hemolytic–uremic syndrome of infancy is a rare disorder that is associated with thrombotic microangiopathy and acute renal failure. It often involves complement dysregulatio...
Assessing Similarity and Diversity of Combinatorial Libraries by Spatial Autocorrelation Functions and Neural Networks (1996)

Kohonen neural networks have been used to show that the combinatorial libraries derived from 1 and 2 are very similar, whereas those obtained with 3 are distinctly different. The depicted Kohonen map indicates that the libraries from 1 and 2 are so similar that they need not both be synthesized for screening. R1R4: one of 18 possible amino acid residues.