gebhart/patrepeval huggingface dataset:
Structure-based ligand discovery for the protein–protein interface of chemokine receptor CXCR4 (2012)

G-protein-coupled receptors (GPCRs) are key signaling molecules and are intensely studied. Whereas GPCRs recognizing small-molecules have been successfully targeted for drug discovery, protein-recognizing GPCRs, such as the chemokine receptors, claim few drugs or even useful small molecule reagents. This reflects both the difficulties that attend protein-protein interface inhibitor discovery, and the lack of structures for these targets. Imminent structure determination of chemokine receptor CXCR4 motivated docking screens for new ligands against a homology model and subsequently the crystal structure. More than 3 million molecules were docked against the model and then against the crystal structure; 24 and 23 high-scoring compounds from the respective screens were tested experimentally. Docking against the model yielded only one antagonist, which resembled known ligands and lacked specificity, whereas the crystal structure docking yielded four that were dissimilar to previously known scaffolds and apparently specific. Intriguingly, several were potent and relatively small, with IC(50) values as low as 306 nM, ligand efficiencies as high as 0.36, and with efficacy in cellular chemotaxis. The potency and efficiency of these molecules has few precedents among protein-protein interface inhibitors, and supports structure-based efforts to discover leads for chemokine GPCRs.
Design and feasibility of active matrix flat panel detector using avalanche amorphous selenium for protein crystallography (2008)

Protein crystallography is the most important technique for resolving the three-dimensional atomic structure of protein by measuring the intensity of its x-ray diffraction pattern. This work proposes a large area flat panel detector for protein crystallography based on direct conversion x-ray detection technique using avalanche amorphous selenium (a-Se) as the high gain photoconductor, and active matrix readout using amorphous silicon (a-Si:H) thin film transistors. The detector employs avalanche multiplication phenomenon of a-Se to make the detector sensitive to each incident x ray. The advantages of the proposed detector over the existing imaging plate and charge coupled device detectors are large area, high dynamic range coupled to single x-ray detection capability, fast readout, high spatial resolution, and inexpensive manufacturing process. The optimal detector design parameters (such as detector size, pixel size, and thickness of a-Se layer), and operating parameters (such as electric field across the a-Se layer) are determined based on the requirements for protein crystallography application. The performance of the detector is evaluated in terms of readout time (<1 s), dynamic range (approximately 10(5)), and sensitivity (approximately 1 x-ray photon), thus validating the detector's efficacy for protein crystallography.
Suppressive effects of various drugs on excitatory responses at trigeminal subnucleus caudalis(VSp.SC) and surrounding nuclei induced by bradykinin application onto the rabbit tooth pulp (1983)

We have reported on the analgesic effects of carbamazepine(CBZ), morphine (MOR) and pentazocine(PZC) on bradykinin(BK)-induced biting responses in behavioral studies. The present investigations were attempted to demonstrate the suppressive effects of these drugs on single neuronal excitatory activities at the VSp.SC and surrounding nuclei of the brain stem induced by BK application onto rabbit tooth pulp. Twenty-seven male albino rabbits weighing 2.2-3.4 kg had their lower incisors implanted with a cannula, and.the head of the animal was flexed to facilitate surgical exposure and recording by tungsten microelectrode of the neurons in VSp.SC and surrounding nuclei under ether anesthesia. The animal was immobilized with gallamine and respired artificially. Repetitive BK applications were done at 30-40 min intervals. On applying BK, paroxysmal discharges of 0.5-2 min episodes were induced within 5 min and followed by repeated episodes of paroxysm lasting for 20-35 min. CBZ(20-30 mg/kg, i.p.) suppressed the BK-induced responses in 9 out of 9 animals(or units), with suppression appearing at 15-20 min, peaking at 60-90 min and recovering at 135 min or more after administration. M0R(2-4 mg/kg,i.v.) and PZC(3-4 mg/kg,i.v.) suppressed 9 of 12 and 3 of 6 animals, respectively. The present study demonstrates that CBZ, MOR and PZC can suppress the BK-induced responses at the VSp.SC and sur-rouding nuclei level, suggesting that the suppressive effects of these drugs on biting responses induced by BK application onto the tooth pulp are probably attributable to their inhibition of nociceptive transmission at the VSp.SC and surrounding nuclei in the brain stem.
Detection and Identification of Previously Unrecognized Microbial Pathogens (1998)

Features of a number of important but poorly explained human clinical syndromes strongly indicate a microbial etiology. In these syndromes, the failure of cultivation-dependent microbial detection methods reveals our ignorance of microbial growth requirements. Sequence-based molecular methods, however, offer alternative approaches for microbial identification directly from host specimens found in the setting of unexplained acute illnesses, chronic inflammatory disease, and from anatomic sites that contain commensal microflora. The rapid expansion of genome sequence databases and advances in biotechnology present opportunities and challenges: identification of consensus sequences from which reliable, specific phylogenetic information can be inferred for all taxonomic groups of pathogens, broad-range pathogen identification on the basis of virulence-associated gene families, and use of host gene expression response profiles as specific signatures of microbial infection.
Serum adipokines might predict liver histology findings in non-alcoholic fatty liver disease (2016)

Certain adipokines may determine the severity of NAFLD histology accurately.
Synthesis of Medium Ring Nitrogen Heterocycles via a Tandem Copper-Catalyzed C−N Bond Formation−Ring-Expansion Process (2004)

A simple method for the preparation of medium ring heterocycles (7-, 8-, 9-, and 10-membered) has been developed. The process employs a Cu-catalyzed coupling of a beta-lactam with an aryl bromide or iodide followed by intramolecular attack of a pendant amino group. In some instances, the intermediate beta-lactam is observable but can be converted to the aza-heterocycle by catalysis. Acetic acid was found to be superior to transition metal complexes as a catalyst for this ring-expansion process.
Fracture Mechanics (2005)

With its combination of practicality, readability, and rigor that is characteristic of any truly authoritative reference and text, Fracture Mechanics: Fundamentals and Applications quickly established itself as the most comprehensive guide to fracture mechanics available. It has been adopted by more than 100 universities and embraced by thousands o
Replication of yellow fever virus in the mouse central nervous system: comparison of neuroadapted and non-neuroadapted virus and partial sequence analysis of the neuroadapted strain (1996)

Serial passage of yellow fever virus (YF17D) in mouse brain enhances neurovirulence, causing a reduction in survival time after intracerebral inoculation of adult mice. To study the biological and genetic basis for this phenomenon, we compared neurovirulence properties of the neuroadapted Porterfield strain (PYF) to a YF17D strain generated from a full-length YF cDNA template (YF5.2iv). Adult mice were infected by olfactory bulb inoculation, which results in widespread distribution of virus throughout the central nervous system. Although PYF and YF5.2iv spread rapidly throughout the neuraxis, maximal titres of PYF in the brain and spinal cord were 1000- to 10,000-fold higher than those of YF5.2iv. Paralysis and death occurred earlier with the PYF strain. Several cDNA clones of the E/NS1 region of the PYF strain were sequenced. Three predicted amino acid changes were consistently observed in the envelope protein of the PYF strain compared to YF5.2iv. Common substitutions were also identified in NS1 and NS2A. The potential contribution of these genetic differences to neurovirulence was evaluated by generating recombinant, intertypic PYF/YF5.2iv viruses. Physical signs of disease and mean spinal cord titres after inoculation of one recombinant were not different from the YF5.2iv parent. Our data indicate that PYF and YF5.2iv differ significantly in their virulence properties, however, common amino acid substitutions in the E/NS1 region of the PYF strain do not determine its enhanced neurovirulence. Other regions of the viral genome may contribute dominant effects on the virulence properties of the PYF strain.
Monocyte-Fibronectin Interactions, Via α5β1 Integrin, Induce Expression of CXC Chemokine-Dependent Angiogenic Activity (2001)

Monocyte-derived macrophages are important sources of angiogenic factors in cancer and other disease states. Upon extravasation from vasculature, monocytes encounter the extracellular matrix. We hypothesized that interaction with extracellular matrix proteins leads monocytes to adopt an angiogenic phenotype. We performed endothelial cell chemotaxis assays on conditioned medium (CM) from monocytes that had been cultured in vitro on various matrix substrates (collagen I, laminin, Matrigel, fibronectin), in the presence of autologous serum, or on tissue culture plastic alone. Monocytes cultured on Matrigel and on fibronectin were the most potent inducers of angiogenic activity compared with tissue culture plastic or autologous serum-differentiated monocytes. This increased angiogenic activity was associated with increased expression of angiogenic CXC chemokines (IL-8, epithelial neutrophil-activating peptide-78, growth-related oncogene alpha, and growth-related oncogene gamma) but not of vascular endothelial growth factor. Additionally, CM from monocytes cultured on fibronectin-depleted Matrigel (MG(FN-)) induced significantly less angiogenic activity than CM from monocytes cultured on control-depleted Matrigel. ELISA analysis of CM from monocytes cultured on MG(FN-) revealed a significant decrease in GRO-alpha and GRO-gamma compared with CM from monocytes cultured on MG. Incubation of monocytes before adherence on fibronectin with PHSCN (a competitive peptide inhibitor of the PHSRN sequence of fibronectin binding via alpha(5)beta(1) integrin) results in diminished expression of angiogenic activity and CXC chemokines compared with control peptide. These data suggest that fibronectin, via alpha(5)beta(1) integrin, promotes CXC chemokine-dependent angiogenic activity from monocytes.
Equalizer training algorithms for multicarrier modulation systems (2002)

In a multicarrier data transmission system the length of a symbol is often limited by the maximum permissible delay of data from input to output. If the length of the impulse response of the channel is not negligible compared to the permitted symbol length, the impulse response can be shortened by passing the received signal through a time-domain equalizer before modulation. The best performance for a given computational complexity can then be achieved by appending to each block of samples of the transmit signal a cyclic prefix that has the same length as the shortened impulse response. Several algorithms for designing the time-domain equalizer, which use adaptation in the frequency domain and windowing in the time domain in order to minimize the mean squared error of the equalized response, are described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Total Systemic Autoregulation in the Dog and Its Inhibition by Baroreceptor Reflexes (1973)

Although many organs maintain constant blood flow despite changes in perfusion pressure, autoregulation in the total systemic circulation has only been reported in animals after destruction of the central nervous system. The present study examined the role of the baroreceptors in this autoregulatory response in open-chest dogs anesthetized with chloralose-urethane. Cardiac output was varied over nearly a twofold range by altering myocardial contractility with either inotropic agents or controlled myocardial ischemia. Cardiac output, determined by dye dilution, and mean aortic pressure stabilized within 3 minutes after the start of infusions of calcium (15-62 mg/min) into the cannulated left coronary artery or the reduction of coronary flow. With bilateral vagotomy and carotid sinus denervation, autoregulation of total peripheral flow was observed. Thus, changes in cardiac output evoked parallel changes in total peripheral resistance and wide variations in aortic pressure. However, with the baroreceptors intact, changes in cardiac output evoked inverse changes in total peripheral resistance which resulted in regulation of aortic pressure. We concluded that autoregulation in peripheral vascular beds could result in autoregulation of total peripheral flow after simple baroreceptor denervation. However, the baroreceptor reflexes normally achieved regulation of aortic pressure by inhibiting autoregulation in much of the peripheral circulation.
Independent Lec1A CHO Glycosylation Mutants Arise from Point Mutations in N-Acetylglucosaminyltransferase I That Reduce Affinity for Both Substrates. Molecular Consequences Based on the Crystal Structure of GlcNAc-TI, (2001)

A key enzyme in regulating the maturation of N-linked glycans is UDP-N-acetylglucosamine:alpha-3-D-mannoside beta-1,2-N-acetylglucosaminyltransferase I (GlcNAc-TI, EC 2.4.1.101). Lec1 CHO cells lack GlcNAc-TI activity and synthesize only the oligomannosyl class of N-glycans. By contrast, Lec1A CHO mutants have weak GlcNAc-TI activity due to the reduced affinity of GlcNAc-TI for both the UDP-GlcNAc and Man(5)GlcNAc(2)Asn substrates. Lec1A CHO mutants synthesize hybrid and complex N-glycans, albeit in reduced amounts compared to parental CHO cells. In this paper, we identify two point mutations that gave rise to the Lec1A phenotype in three independent Lec1A CHO mutants. The G634A mutation in Lec1A.2C converts an aspartic acid to an asparagine at amino acid 212, disrupting a conserved DXD motif (E(211)DD(213) in all GlcNAc-TIs) that makes critical interactions with bound UDP-GlcNAc and Mn(2+) ion in rabbit GlcNAc-TI. The C907T mutation in Lec1A.3E and Lec1A.5J converts an arginine conserved in all GlcNAc-TIs to a tryptophan at amino acid 303, altering interactions that are important in stabilizing a critical structural element in rabbit GlcNAc-TI. Correction of each mutation by site-directed mutagenesis restored their GlcNAc-TI activity and lectin binding properties to parental levels. The effect of the two amino acid changes on GlcNAc-TI catalysis is discussed in relation to the crystal structure of rabbit GlcNAc-TI complexed with manganese and UDP-GlcNAc.
Review: Bariatric surgery: to treat diabesity (2009)

In obese patients bariatric surgery is increasing in popularity as a strategy to promote, and maintain, weight loss. In obese type 2 diabetes bypass, bariatric surgery improves glycaemic control — often to a greater extent than would be anticipated by weight loss alone. Surgical bypass procedures appear to initially offer a greater glucose-lowering effect than surgical restriction procedures. This review considers the rationale for bariatric surgery as a treatment for diabesity and the implications of the different procedures on the secretion and action of enteral hormones.
Antitumor activity of a C-raf antisense oligonucleotide in combination with standard chemotherapeutic agents against various human tumors transplanted subcutaneously into nude mice. (1997)

A 20-mer phosphorothioate oligodeoxynucleotide (ODN) directed against human C-raf kinase (CGP 69846A or ISIS 5132) was analyzed for its antitumor activity either alone or in combination therapy. Combination studies with CGP 69846A and standard chemotherapeutic agents (cisplatin, mitomycin C, tamoxifen, or Adriamycin) were performed in nude mice that had been transplanted s.c. with a variety of human tumors (breast, prostate, colon, small cell lung, large cell lung, and squamous lung carcinomas). For the majority of the combinations studied, additive antitumor effects with CGP 69846A and the cytotoxins were found. The combination of CGP 69846A with cisplatin or mitomycin C showed superadditive antitumor activities against NCI-H69 small cell lung carcinomas with complete tumor responses. CGP 69846A, in combination with cisplatin, showed superadditive antitumor effects against PC3 human prostate carcinomas with tumor cures, and in combination with mitomycin C, superadditive antitumor effects of CGP 69846A with tumor cures against NCI-H460 large cell lung carcinoma were found. These effects appeared to be sequence-specific because a mismatched control ODN was completely without effect as a single agent against NCI-H69 human small cell lung cancers. The combination of the mismatched control ODN with mitomycin C or cisplatin did not influence the antitumor activity of the cytotoxins against NCI-H69 human small cell lung cancers, indicating that the superadditive antitumor effects observed for CGP 69846A in combination with cisplatin or mitomycin C are the result of a sequence-specific mechanism of action in NCI-H69 human small cell lung cancers.
Adaptive-Size Reservoir Sampling over Data Streams (2007)

Reservoir sampling is a well-known technique for sequential random sampling over data streams. Conventional reservoir sampling assumes a fixed-size reservoir. There are situations, however, in which it is necessary and/or advantageous to adaptively adjust the size of a reservoir in the middle of sampling due to changes in data characteristics and/or application behavior. This paper studies adaptive size reservoir sampling over data streams considering two main factors: reservoir size and sample uniformity. First, the paper conducts a theoretical study on the effects of adjusting the size of a reservoir while sampling is in progress. The theoretical results show that such an adjustment may bring a negative impact on the probability of the sample being uniform (called uniformity confidence herein). Second, the paper presents a novel algorithm for maintaining the reservoir sample after the reservoir size is adjusted such that the resulting uniformity confidence exceeds a given threshold. Third, the paper extends the proposed algorithm to an adaptive multi-reservoir sampling algorithm for a practical application in which samples are collected from memory-limited wireless sensor networks using a mobile sink. Finally, the paper empirically examines the adaptivity of the multi-reservoir sampling algorithm with regard to reservoir size and sample uniformity using real sensor networks data sets.
ChemInform Abstract: Synthesis of Amino‐, Hydroxy‐, and Thio‐Derivatives of 1,3,5‐Triazine Bearing Diphenylamine Fragments. (1996)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Formation of the Dehydrogenases for Lactate, Ethanol and Butanediol in the Strictly Aerobic Bacterium Alcaligenes eutrophus (1980)

Lactate, ethanol and butanediol were excreted when Alcaligenes eutrophus was exposed to severely restricted aeration. This indicated the presence of dehydrogenases which are not normally present in aerobically grown cultures of this strictly aerobic bacterium. When grown in the presence of measurable dissolved oxygen concentrations. A. eutrophus strain N9A and a double mutant defective in the formation of poly-3-hydroxybutanoic acid and in the utilization of 3-hydroxybutanoate did not synthesize alcohol, lactate or butanediol dehydrogenases. However, when bacteria were subsequently incubated for 10 to 25 h under restricted aeration conditions that permitted respiration rates of only about 3 to 15% of the maximum value, the above enzymes were formed with specific activities up to 0·75 μmol min−1 (mg protein)−1. The identity of metabolites excreted as well as the nature of the enzymes formed could be correlated with the distinctive relative respiration rates enforced on the bacteria during incubation. The results indicate that A. eutrophus contains genetic information which is not expressed under ordinary cultural conditions. The significance for retention of the dormant genetic material in strictly aerobic bacteria is discussed.
Direct Observation of Anion‐Mediated Translocation of Fluorescent Oligoarginine Carriers into and across Bulk Liquid and Anionic Bilayer Membranes (2004)

The recent hypothesis that counteranion-mediated dynamic inversion of charge and solubility might contribute to diverse functions of oligoarginines in biomembranes was tested with two fluorescently labelled oligomers, FL-R(8), one of the most active cell-penetrating peptides, and its longer version, FL-R(16). We report evidence for counteranion-mediated phase transfer from water into bulk chloroform and anionic lipid-bilayer membranes as well as reverse-phase transfer from bulk chloroform and across intact lipid-bilayer membranes into water. The differences found between FL-R(8) and FL-R(16) with regard to location in the bilayer and reverse-phase transfer from bulk and lipid-bilayer membranes into water implied that the reported results may be relevant for biological function.
Eight Calves Cloned from Somatic Cells of a Single Adult (1998)

Eight calves were derived from differentiated cells of a single adult cow, five from cumulus cells and three from oviductal cells out of 10 embryos transferred to surrogate cows (80 percent success). All calves were visibly normal, but four died at or soon after birth from environmental causes, and postmortem analysis revealed no abnormality. These results show that bovine cumulus and oviductal epithelial cells of the adult have the genetic content to direct the development of newborn calves.
Mannan-binding lectin activates C3 and the alternative complement pathway without involvement of C2 (2006)

Lectin pathway activation of C3 is known to involve target recognition by mannan-binding lectin (MBL) or ficolins and generation of classical pathway C3 convertase via cleavage of C4 and C2 by MBL-associated serine protease 2 (MASP-2). We investigated C3 activation in C2-deficient human sera and in sera with other defined defects of complement to assess other mechanisms through which MBL might recruit complement. The capacity of serum to support C3 deposition was examined by ELISA using microtiter plates coated with O antigen-specific oligosaccharides derived from Salmonella typhimurium, S. thompson, and S. enteritidis corresponding to serogroups B, C, and D (BO, CO, and DO). MBL bound to CO, but not to BO and DO, and efficiently supported C3 deposition in the absence of C2, C4, or MASP-2. The existence of an MBL-dependent C2 bypass mechanism for alternative pathway-mediated C3 activation was clearly demonstrated using CO, solid-phase mannan, and E. coli LPS. MASP-1 might contribute, but was not required for C3 deposition in the model used. Independent of MBL, specific antibodies to CO supported C3 deposition through classical and alternative pathways. MBL-dependent C2 bypass activation could be particularly important in various inherited and acquired complement deficiency states.