gebhart/patrepeval huggingface dataset:
Vascular Endothelial-Junctional Adhesion Molecule (VE-JAM)/JAM 2 Interacts with T, NK, and Dendritic Cells Through JAM 3 (2002)

Screening expressed sequence tag databases for endothelial-specific homologs to human junctional adhesion molecule (JAM) and A33-Ag, we identified a protein of 298 aa that represents the recently described vascular endothelial-JAM (VE-JAM)/JAM 2. We confirmed VE-JAM/JAM 2 expression to be restricted to the high endothelial venule of tonsil and lymph nodes, and we further expanded the localization to the endothelium of arterioles in and around inflammatory and tumor foci. In our functional characterizations of VE-JAM/JAM 2, we discovered that it can function as an adhesive ligand for the T cell line J45 and can interact with GM-CSF/IL-4-derived peripheral blood dendritic cells, circulating CD56(+) NK cells, circulating CD56(+)CD3(+) NK/T cells, and circulating CD56(+)CD3(+)CD8(+) cytolytic T cells. In the course of our studies, we also isolated and characterized the functional VE-JAM/JAM 2 receptor, which, upon cloning, turned out to be a submitted sequence representing JAM 3 (accession number NP 113658). With these understandings, we have characterized a protein-interacting pair that can be important in the role of T, NK, and dendritic cell trafficking and inflammation.
Attachment of protein affinity-labeling reagents of variable length and amino acid specificity to E. coli tRNAfMet (1981)

Transamination with bifunctional amines in the presence of bisulfite has been used to attach side chains of variable length to the N4-position of single stranded cytidine residues in E. coli tRNAfMet. Such side chains, terminating in reactive primary amino groups, have been coupled to a variety of N-hydroxysuccinimide esters. The resulting modified tRNAs carry protein affinity labeling groups capable of covalent reaction with a variety of amino acids.
Persistent Pulmonary Hypertension of the Newborn in the Era Before Nitric Oxide: Practice Variation and Outcomes (2000)

Hyperventilation and alkali infusion are not equivalent in their outcomes in neonates with PPHN. Randomized trials are needed to evaluate the role of these common therapies.
Pharmacological Studies on Lamotrigine, A Novel Potential Antiepileptic Drug (1986)

Lamotrigine (LTG) [3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine] is a novel anticonvulsant chemically unrelated to current antiepileptic drugs and with a pharmacological profile similar to that of phenytoin. The effect of LTG has been compared with that of phenytoin, on the release of endogenous amino acids and radiolabelled acetylcholine evoked by veratrine or potassium, from slices of rat cerebral cortex in vitro. Both veratrine and potassium evoked a marked release of glutamate and gamma-aminobutyric acid (GABA), with a more moderate release of aspartate. LTG inhibited veratrine-evoked release of glutamate and aspartate, with ED50 values of 21 microM for both amino acids, but LTG was less potent in the inhibition of GABA release (ED50 = 44 microM). At concentrations up to 300 microM, LTG had no effect on potassium-evoked amino acid release or on spontaneous release. Also, LTG was some five times less potent in the inhibition of veratrine-evoked [3H]acetylcholine release (ED50 = 100 microM) than in glutamate or aspartate release. The total lack of effect of LTG on potassium-evoked release and the potent effect on veratrine-evoked release (at concentrations found in rat brain after anticonvulsant doses) strongly suggest that LTG acts at voltage-sensitive sodium channels to stabilise neuronal membranes and inhibit transmitter release, principally glutamate. The role of glutamate in the aetiology of epilepsy is discussed.
Non-alcoholic steatohepatitis: the therapeutic challenge of a global epidemic. (2012)

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. Nonalcoholic steatohepatitis (NASH) reflects severe liver disease within the NAFLD spectrum and can progress to end-stage liver disease. Within this manuscript we review the available evidence for the treatment of NASH as well as the newer therapeutic agents that are currently being investigated.
Molecular targeting therapy of cancer: drug resistance, apoptosis and survival signal (2003)

Recent progress in the development of molecular cancer therapeutics has revealed new types of antitumor drugs, such as Herceptin, Gleevec, and Iressa, as potent therapeutics for specific tumors. Our work has focused on molecular cancer therapeutics, mainly in the areas of drug resistance, apoptosis and apoptosis resistance, and survival-signaling, which is related to drug resistance. In this review, we describe our research on molecular cancer therapeutics, including molecular mechanisms and therapeutic approaches. Resistance to chemotherapeutic drugs is a principal problem in the treatment of cancer. P-Glycoprotein (P-gp), encoded by the MDR1 gene, is a multidrug transporter and has a major role in multidrug resistance (MDR). Targeting of P-gp by small-molecular compounds and/or antibodies is an effective strategy to overcome MDR in cancer, especially hematologic malignancies. Several P-gp inhibitors have been developed and are currently under clinical phased studies. In addition to the multidrug transporter proteins, cancer cells have several drug resistance mechanisms. Solid tumors are often placed under stress conditions, such as glucose starvation and hypoxia. These conditions result in topo II poison resistance that is due to proteasome-mediated degradation of DNA topoisomerases. Proteasome inhibitors effectively prevent this stress-induced drug resistance. Glyoxalase I, which is often elevated in drug- and apoptosis-resistant cancers, offers another possibility for overcoming drug resistance. It plays a role in detoxification of methylglioxal, a side product of glycolysis, which is highly reactive with DNA and proteins. Inhibitors of glyoxalase I selectively kill drug-resistant tumors that express glyoxalase I. Finally, the susceptibility of tumor cells to apoptosis induced by antitumor drugs appears to depend on the balance between pro-apoptotic and survival (anti-apoptotic) signals. PI3K-Akt is an important survival signal pathway, that has been shown to be the target of various antitumor drugs, including UCN-01 and geldanamycin, new anticancer drugs under clinical evaluation. Our present studies provide novel targets for future effective molecular cancer therapeutics.
Prostacyclin release from endothelial cells, induced by defibrotide treatment, favours the function of grafted rat hearts and kidneys. (1991)

Defibrotide, a single-stranded DNA fraction obtained from mammalian lungs and able to increase prostacyclin production by endothelial cells, has been shown to be efficient in protecting rat organs (heart, kidney and liver) from ischaemic damage. We studied the efficacy of the drug in preserving the function of rat heart and kidney submitted to isotransplantation. Defibrotide was administered to donor Wistar rats at the dose of 32 mg/kg in 1.5 ml of saline. Heart and kidney were isolated and cold-preserved in buffered phosphate medium and continuously infused with defibrotide (32 mg/h) through the innominate or renal artery. Recipient Wistar rats were treated with defibrotide before and after transplantation at the dose of 32 mg/kg/day. Controls were treated with the vehicle of the drug. The function of isografted organs was evaluated at 12 and 24 h and at 2, 4 and 7 days from grafting. Heart function was evaluated by studying creatinine phosphokinase (CPK) and lactic dehydrogenase (LDH) activities of myocardial tissue. Renal function was evaluated by studying serum creatinine and urea levels of kidney-grafted rats. CPK and LDH activities were found to be significantly higher in defibrotide-treated rats than in controls. Creatinine and urea levels remained significantly lower in defibrotide-treated rats than in the controls. The results of the present work indicate that defibrotide treatment is useful to maintain the functionality of grafted hearts and kidneys.
In vitro and in vivo evaluation of a novel recombinant immunotoxin of ranpirnase fused to a humanized anti-EGP-1 antibody, hRS7, for the potential treatment of prostate and lung cancers. (2007)

4795 Introduction: We have generated a novel immunotoxin by fusing ranpirnase (Rap), an amphibian RNase, to hRS7, an internalizing humanized anti-EGP-1 antibody, using the method described previously (Blood 2005; 106: 4308-4314). Since EGP-1 is expressed abundantly in certain human cancer cell lines such as PC-3 of prostate cancer, Calu-3 of NSCLC, and ME180 of cervical cancer, the immunotoxin is a potential therapeutic for these solid tumors. Methods: The Rap gene was inserted at the N-terminus of the light chain in the expression vector of hRS7. SP2/0 mouse myeloma cells were transfected, and positive clones identified by ELISA screening. The fusion protein (Rap-hRS7) was purified by protein A and characterized by a variety of in vitro techniques. In vivo therapeutic efficacy was evaluated in SCID mice bearing either PC-3 or Calu-3 xenografts. Results: Rap-hRS7 was shown to be a single peak by SE-HPLC and have binding affinity to PC-3 or Calu-3 similar to hRS7. Whereas the EC50 of RNase activity, as measured in cell-free systems by the IVTT assay, was 1400 pM for Rap-hRS7 compared to 30 pM for free Rap, the in vitro cytotoxicity of the immunotoxin on Calu-3 and PC-3, as measured by the MTS assay, was 50-and 30-fold higher than free Rap. When given a single dose of 50 μg, the immunotoxin was able to extend the median survival time of treated animals to 96 days from 55 days of the untreated group (P
Acylation of 2,5-Dimethoxycarbonyl[60]fulleropyrrolidine and Synthesis of Its Multifullerene Derivatives (2002)

2,5-Dimethoxycarbonyl[60]fulleropyrrolidine (1) is acylated with various chlorocarbonyl compounds to give fullerene derivatives with the general formula C(60)(MeOOCCH)(2)NC(O)R, R = (CH(2))(5)Br, (CH(2))(8)C(O)Cl (3), (CH(2))(4)C(O)Cl, or cis-C(6)H(4)(C(O)Cl. The monoacylated sebacoyl derivative 3 readily reacts with alcohols and amines such as methanol, diethylamine, glycine methyl ester, and aza-18-crown-6 through the remaining chlorocarbonyl group. Chromatography of 3 on silica gel converts it into the corresponding acid C(60)(MeOOCCH)(2)NC(O)(CH(2))(8)COOH (4). Treating 4 with PCl(5) regenerates the precursor 3 quantitatively. Piperazine reacts with 4 in the presence of DCC and BtOH to form a bisfullerene derivative in which two sebacoyl chains and the piperazine act as the bridge between two molecules of 1. Other molecules with multifunctional groups react with 4 similarly to form multifullerene derivatives. NMR data indicate that the rotation of the relatively bulky phthaloyl group is hindered around the amide bond N [bond] C(O), the rotation barrier of which is 15.06 kcal/mol. The relative stereochemistry of the 2,5-dimethoxycarbonyl groups is established by (1)H NMR spectra and further confirmed by resolution of the enantiomeric 2,5-trans-isomer of the starting material 1.
Diagnosis of Sleep Apnea by Automatic Analysis of Nasal Pressure and Forced Oscillation Impedance (2002)

Detecting and differentiating central and obstructive respiratory events is an important aspect of the diagnosis of sleep-related breathing disorders with respect to the choice of an appropriate treatment. The purpose of this study was to evaluate the performance of a new algorithm for automated detection and classification of apneas and hypopneas, compared with visual analysis of standard polysomnographic signals. The algorithm is based on time series analysis of nasal mask pressure and a forced oscillation signal related to mechanical respiratory input impedance, measured at a frequency of 20 Hz throughout the night. The method was applied to all-night measurements on 19 subjects. Two experts in sleep medicine independently scored the corresponding simultaneously recorded polysomnographic signals. Evaluating the agreement between two scorers by a weighted kappa statistic on a second-by-second basis, we found that inter-expert variability and the discrepancy between automatic analysis and visual analysis performed by an expert were not significantly different. Implementation of this algorithm in a device for home monitoring of breathing during sleep might aid in the differential diagnosis of sleep-related breathing disorders and/or as a means for follow-up and treatment control.
The crystal structure of human IRE1 luminal domain reveals a conserved dimerization interface required for activation of the unfolded protein response (2006)

The unfolded protein response (UPR) is an evolutionarily conserved mechanism by which all eukaryotic cells adapt to the accumulation of unfolded proteins in the endoplasmic reticulum (ER). Inositol-requiring kinase 1 (IRE1) and PKR-related ER kinase (PERK) are two type I transmembrane ER-localized protein kinase receptors that signal the UPR through a process that involves homodimerization and autophosphorylation. To elucidate the molecular basis of the ER transmembrane signaling event, we determined the x-ray crystal structure of the luminal domain of human IRE1alpha. The monomer of the luminal domain comprises a unique fold of a triangular assembly of beta-sheet clusters. Structural analysis identified an extensive dimerization interface stabilized by hydrogen bonds and hydrophobic interactions. Dimerization creates an MHC-like groove at the interface. However, because this groove is too narrow for peptide binding and the purified luminal domain forms high-affinity dimers in vitro, peptide binding to this groove is not required for dimerization. Consistent with our structural observations, mutations that disrupt the dimerization interface produced IRE1alpha molecules that failed to either dimerize or activate the UPR upon ER stress. In addition, mutations in a structurally homologous region within PERK also prevented dimerization. Our structural, biochemical, and functional studies in vivo altogether demonstrate that IRE1 and PERK have conserved a common molecular interface necessary and sufficient for dimerization and UPR signaling.
Microfabricated alkali atom vapor cells (2004)

We describe the fabrication of chip-sized alkali atom vapor cells using silicon micromachining and anodic bonding technology. Such cells may find use in highly miniaturized atomic frequency references or magnetometers. The cells consist of cavities etched in silicon, with internal volumes as small as 1 mm3. Two techniques for introducing cesium and a buffer gas into the cells are described: one based on chemical reaction between cesium chloride and barium azide, and the other based on direct injection of elemental cesium within a controlled anaerobic environment. Cesium optical absorption and coherent population trapping resonances were measured in the cells.
Analysis of proteome dynamics in the mouse brain (2010)

Advances in systems biology have allowed for global analyses of mRNA and protein expression, but large-scale studies of protein dynamics and turnover have not been conducted in vivo. Protein turnover is an important metabolic and regulatory mechanism in establishing proteome homeostasis, impacting many physiological and pathological processes. Here, we have used organism-wide isotopic labeling to measure the turnover rates of approximately 2,500 proteins in multiple mouse tissues, spanning four orders of magnitude. Through comparison of the brain with the liver and blood, we show that within the respective tissues, proteins performing similar functions often have similar turnover rates. Proteins in the brain have significantly slower turnover (average lifetime of 9.0 d) compared with those of the liver (3.0 d) and blood (3.5 d). Within some organelles (such as mitochondria), proteins have a narrow range of lifetimes, suggesting a synchronized turnover mechanism. Protein subunits within complexes of variable composition have a wide range of lifetimes, whereas those within well-defined complexes turn over in a coordinated manner. Together, the data represent the most comprehensive in vivo analysis of mammalian proteome turnover to date. The developed methodology can be adapted to assess in vivo proteome homeostasis in any model organism that will tolerate a labeled diet and may be particularly useful in the analysis of neurodegenerative diseases in vivo.
Patterning: Principles and Some New Developments (2004)

Abstract This article provides an overview of various patterning methodologies, and it is organized into three major sections: generation of patterns, replication of patterns, and three‐dimensional patterning. Generation of patterns from scratch is usually accomplished by serial techniques that are able to provide arbitrary features. The writing process can be carried out in many different ways. It can be achieved using a rigid stylus; or a focused beam of photons, electrons, and other energetic particles. It can also be accomplished using an electrical or magnetic field; or through localized add‐on of materials such as a liquid‐like ink from an external source. In addition, some ordered but relatively simple patterns can be formed by means of self‐assembly. In replication of patterns, structural information from a mask, master, or stamp is transferred to multiple copies with the use of an appropriate material. The patterned features on a mask are mainly used to direct a flux of radiation or physical matter from a source onto a substrate, whereas a master/stamp serves as the original for replication based on embossing, molding, or printing. The last section of this article deals with three‐dimensional patterning, where both vertical and lateral dimensions of a structure need to be precisely controlled to generate well‐defined shapes and profiles. The article is illustrated with various examples derived from recent developments in this field.
Mammalian Prenylcysteine Carboxyl Methyltransferase Is in the Endoplasmic Reticulum (1998)

Prenylcysteine carboxyl methyltransferase (pcCMT) is the third of three enzymes that posttranslationally modify C-terminal CAAX motifs and thereby target CAAX proteins to the plasma membrane. Here we report the molecular characterization and subcellular localization of the first mammalian (human myeloid) pcCMT. The deduced amino acid sequence of mammalian pcCMT predicts a multiple membrane-spanning protein with homologies to the yeast pcCMT, STE14, and the mammalian band 3 anion transporter. The human gene complemented a ste14 mutant. pcCMT mRNAs were ubiquitously expressed in human tissues. An anti-pcCMT antiserum detected a 33-kDa protein in myeloid cell membranes. Ectopically expressed recombinant pcCMT had enzymatic activity identical to that observed in neutrophil membranes. Mammalian pcCMT was not expressed at the plasma membrane but rather restricted to the endoplasmic reticulum. Thus, the final enzyme in the sequence that modifies CAAX motifs is located in membranes topologically removed from the CAAX protein target membrane.
Abnormal Neural Synchrony in Schizophrenia (2003)

Schizophrenia has been conceptualized as a failure of cognitive integration, and abnormalities in neural circuitry (particularly inhibitory interneurons) have been proposed as a basis for this disorder. We used measures of phase locking and phase coherence in the scalp-recorded electroencephalogram to examine the synchronization of neural circuits in schizophrenia. Compared with matched control subjects, schizophrenia patients demonstrated: (1) absence of the posterior component of the early visual gamma band response to Gestalt stimuli; (2) abnormalities in the topography, latency, and frequency of the anterior component of this response; (3) delayed onset of phase coherence changes; and (4) the pattern of anterior-posterior coherence increases in response to Gestalt stimuli found in controls was replaced by a pattern of interhemispheric coherence decreases in patients. These findings support the hypothesis that schizophrenia is associated with impaired neural circuitry demonstrated as a failure of gamma band synchronization, especially in the 40 Hz range.
Total-Ionizing-Dose Effects on Resistance Stability of Programmable Metallization Cell Based Memory and Selectors (2016)

In this paper, the operation and effects of radiation on Programmable Metallization Cells (PMC) memory and selector devices are analyzed and discussed. The Ag- or Cu-Ge <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">30</sub> Se <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">70</sub> devices demonstrate non-volatile memory switching characteristics while the Ag- or Cu-SiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> devices show a volatile threshold switching property. The impact of total ionizing dose from gamma-ray irradiation on both device types is investigated experimentally. It is found that the virgin and high-resistance state of Ge <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">30</sub> Se <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">70</sub> memory devices degrade after gamma-ray exposure while they are well preserved in SiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> selector devices.
Antibiotic Susceptibilities of Pseudomonas aeruginosa Isolates Derived from Patients with Cystic Fibrosis under Aerobic, Anaerobic, and Biofilm Conditions (2005)

Recent studies have determined that Pseudomonas aeruginosa can live in a biofilm mode within hypoxic mucus in the airways of patients with cystic fibrosis (CF). P. aeruginosa grown under anaerobic and biofilm conditions may better approximate in vivo growth conditions in the CF airways, and combination antibiotic susceptibility testing of anaerobically and biofilm-grown isolates may be more relevant than traditional susceptibility testing under planktonic aerobic conditions. We tested 16 multidrug-resistant isolates of P. aeruginosa derived from CF patients using multiple combination bactericidal testing to compare the efficacies of double and triple antibiotic combinations against the isolates grown under traditional aerobic planktonic conditions, in planktonic anaerobic conditions, and in biofilm mode. Both anaerobically grown and biofilm-grown bacteria were significantly less susceptible (P < 0.01) to single and combination antibiotics than corresponding aerobic planktonically grown isolates. Furthermore, the antibiotic combinations that were bactericidal under anaerobic conditions were often different from those that were bactericidal against the same organisms grown as biofilms. The most effective combinations under all conditions were colistin (tested at concentrations suitable for nebulization) either alone or in combination with tobramycin (10 microg ml(-1)), followed by meropenem combined with tobramycin or ciprofloxacin. The findings of this study illustrate that antibiotic sensitivities are dependent on culture conditions and highlight the complexities of choosing appropriate combination therapy for multidrug-resistant P. aeruginosa in the CF lung.