gebhart/patrepeval huggingface dataset:
Synthesis and structure-activity studies of a series of spirooxazolidine-2,4-diones: 4-oxa-analogs of the muscarinic agonist 2-ethyl-8-methyl-2,8-diazaspiro[4.5]decane-1,3-dione (1993)

A series of spirooxazolidine-2,4-dione derivatives related to the putative M1 agonist 2-ethyl-8-methyl-2,8-diazaspiro[4.5]decane-1,3-dione (RS86; 1) were synthesized. The compounds were evaluated as cholinergic agents in in vitro binding assays and in in vivo pharmacological tests including antiamnesic effects using scopolamine-treated mice, hypothermia, and salivation in mice. Four compounds (5a,c,f and 17a) exhibited affinity for cortical M1 receptors and reversed scopolamine-induced impairment of mouse passive avoidance tasks, as did 1. Among these compounds, only 5a exhibited M1-receptor stimulating activity in pithed rats. Structural requirements for muscarinic activity in this series of spirooxazolidine-2,4-dione derivatives were as strict as those reported for spirosuccinimide derivatives including 1. The antiamnesic dose of 3-ethyl-8-methyl-1-oxa-3,8-diazaspiro[4.5]decane-2,4-dione (5a) was 2 orders of magnitude lower than the doses inducing hypothermia and salivation, in contrast to 1 for which the former dose was only 5-10-fold lower than the latter. These results suggest that the 8-azaspiro[4.5]decane skeleton represents a useful template for designing new muscarinic agonists as antidementia drugs.
Triple-helix formation by an oligonucleotide containing one (dA)12 and two (dT)12 sequences bridged by two hexaethylene glycol chains (1992)

The triple-helix formation by the oligonucleotide (dA)12-x-(dT)12-x-(dT)12, where x is a hexaethylene glycol group, was investigated by thermal denaturation analysis and circular dichroism spectroscopy. Thermal denaturation analysis showed that this single-stranded oligonucleotide is able to fold back on itself twice to give a triple helix at low temperature. Upon an increase in the temperature, two cooperative transitions were observed: formation of a double-stranded structure with a dangling x-(dT)12 extremity, then formation of a single-stranded coil structure. Due to the intramolecular character of the transition, the triplex is much more stable than that formed by the reference mixture (dA)12 + 2(dT)12. In 0.1 M NaCl, the triplex-to-coil transition occurred at about 30 degrees C whereas the duplex-to-coil was at about 60 degrees C. Upon an increase in the salt, the increase of temperature corresponding to the triplex-to-duplex transition was larger than that of the duplex-to-coil transition. MgCl2 showed higher efficiency than NaCl to promote triplex or duplex formation. The thermodynamic parameters delta H and delta S were determined at various ionic strengths for both transitions. Both the enthalpy change and entropy change associated with triplex-to-duplex transition (Hoogsteen base pairing) were smaller than those associated to the duplex-to-coil transition (Watson-Crick base pairing). When the ionic strength increased, the parameters -delta H and -delta S showed a very small decrease for the duplex-to-coil transition whereas a strong increase was observed with the triplex-to-duplex transition.(ABSTRACT TRUNCATED AT 250 WORDS)
Ursodiol for Primary Sclerosing Cholangitis (1997)

In a group of patients with well-defined primary sclerosing cholangitis, ursodiol provided no clinical benefit.
Genome-wide detection of alternative splicing in expressed sequences of human genes (2001)

We have identified 6201 alternative splice relationships in human genes, through a genome-wide analysis of expressed sequence tags (ESTs). Starting with approximately 2.1 million human mRNA and EST sequences, we mapped expressed sequences onto the draft human genome sequence and only accepted splices that obeyed the standard splice site consensus. A large fraction (47%) of these were observed multiple times, indicating that they comprise a substantial fraction of the mRNA species. The vast majority of the detected alternative forms appear to be novel, and produce highly specific, biologically meaningful control of function in both known and novel human genes, e.g. specific removal of the lysosomal targeting signal from HLA-DM beta chain, replacement of the C-terminal transmembrane domain and cytoplasmic tail in an FC receptor beta chain homolog with a different transmembrane domain and cytoplasmic tail, likely modulating its signal transduction activity. Our data indicate that a large proportion of human genes, probably 42% or more, are alternatively spliced, but that this appears to be observed mainly in certain types of molecules (e.g. cell surface receptors) and systemic functions, particularly the immune system and nervous system. These results provide a comprehensive dataset for understanding the role of alternative splicing in the human genome, accessible at http://www.bioinformatics.ucla.edu/HASDB.
Actively Tuned and Spatially Trapped Polaritons (2005)

We report active tuning of the polariton resonance of quantum well excitons in a semiconductor microcavity using applied stress. Starting with the quantum well exciton energy higher than the cavity photon mode, we use stress to reduce the exciton energy and bring it into resonance with the photon mode. At the point of zero detuning, line narrowing and strong increase of the photoluminescence are seen. By the same means, we create an in-plane harmonic potential for the polaritons, which allows trapping, potentially making Bose-Einstein condensation of polaritons analogous to trapped atoms possible. We demonstrate drift of the polaritons into this trap.
Laryngeal Pacing in Unilateral Vocal Cord Paralysis: An Experimental Study (1990)

In an attempt to remobilize a unilaterally paralyzed vocal cord, experiments were made in five adult dogs. Adduction of the paralyzed vocal cord for phonation in synchrony with the intact cord was achieved by electrical stimulation of the adductor muscles that was triggered by the signals from the cricothyroid muscle. The difference in the level of action potentials of the cricothyroid muscle between during phonation and during respiration was used for setting the threshold so as to differentiate phonation from respiration. Nearly synchronous movement of the two vocal cords thereby attained during phonation greatly improved the voice quality that was hoarse without the paced stimulation.
Manipulation of Ascitic Fluid Pressure in Cirrhotics to Optimize Hemodynamic and Renal Function (1988)

Intra-abdominal pressure (IAP), measured via a transurethral catheter, hemodynamic, and renal functions were evaluated in 25 cirrhotic patients admitted to ICU with variceal bleeding, tense ascites, and peripheral edema. In patients with an IAP greater than 25 cm H2O, a paracentesis was performed to decrease the IAP by 10 cm H2O. After paracentesis, a decrease in the IAP from 33.47 to 19.06 cm H2O (p less than 0.001) resulted in a decrease in total peripheral resistance (TPR) (p less than 0.01) and a significant increase in cardiac index (CI) (p less than 0.001), stroke index (p less than 0.001), left ventricular stroke work (LVSW) (p less than 0.01), and right ventricular stroke work (p less than 0.01). The therapeutic effects of paracentesis on renal function were: a decrease in BUN and serum creatinine (p less than 0.001) and an increase in the creatinine clearance (Ccr) (p less than 0.001), urine volume (p less than 0.001), osmolar clearance (Cosm) (p less than 0.001), and urine creatinine (p less than 0.001) values. The IAP correlated directly with the TPR (r = +0.35, p less than 0.01) and inversely with the CI (r = -0.39, p less than 0.001) and LVSW (r = -0.37, p less than 0.001) in the 126 studies of IAP performed with the 25 patients. IAP also correlated directly with BUN (r = 0.40, p less than 0.001), serum creatinine (r = 0.28, p less than 0.01), and free water clearance (CH2O) (r = 0.3, p less than 0.001); IAP correlated negatively with Ccr (r = -0.54, p less than 0.001) and Cosm (r = -0.43, p less than 0.001). In critically ill cirrhotic patients, IAP, when measured noninvasively via a bladder catheter, is an accurate and useful method to follow manipulation of ascitic fluid pressure quantitatively in order to optimize hemodynamic and renal function.
Characterizing a thermostable Cas9 for bacterial genome editing and silencing (2017)

CRISPR-Cas9-based genome engineering tools have revolutionized fundamental research and biotechnological exploitation of both eukaryotes and prokaryotes. However, the mesophilic nature of the established Cas9 systems does not allow for applications that require enhanced stability, including engineering at elevated temperatures. Here we identify and characterize ThermoCas9 from the thermophilic bacterium Geobacillus thermodenitrificans T12. We show that in vitro ThermoCas9 is active between 20 and 70 °C, has stringent PAM-preference at lower temperatures, tolerates fewer spacer-protospacer mismatches than SpCas9 and its activity at elevated temperatures depends on the sgRNA-structure. We develop ThermoCas9-based engineering tools for gene deletion and transcriptional silencing at 55 °C in Bacillus smithii and for gene deletion at 37 °C in Pseudomonas putida. Altogether, our findings provide fundamental insights into a thermophilic CRISPR-Cas family member and establish a Cas9-based bacterial genome editing and silencing tool with a broad temperature range.
Human cardiac stem cells inhibit lymphocyte proliferation through paracrine mechanisms that correlate with indoleamine 2,3-dioxygenase induction and activity (2018)

Transplantation of allogeneic human cardiac/stem progenitor cells (hCSCs) is currently being tested in several phase I/II clinical trials as a novel and promising therapy for restoration of myocardial tissue function in acute myocardial infarction (AMI) patients. Previous findings demonstrate that these cells have an immune suppressive profile interacting with different populations from the immune system, resulting in overall attenuation of myocardial inflammation. However, transplanted hCSCs are still recognized and cleared from the injured site, impairing long retention times in the tissue that could translate into a higher clinical benefit.In this work, through modeling allogeneic hCSC/T lymphocyte interaction in vitro by direct contact, transwell inserts, and hCSC conditioned medium, our results demonstrate that hCSCs exert an immune-suppressive effect on T lymphocyte proliferation not only through the previously described cell contact-dependent programmed cell death-1 (PD1)/programmed death ligand-1 (PDL-1) axis but also through a paracrine mechanism associated with indoleamine 2,3-dioxygenase (IDO) enzyme-mediated tryptophan metabolism. Such findings constitute a step forward in better understanding the mechanisms of action of transplanted hCSCs in allogeneic settings.
Microscopic model for enhanced dielectric constants in low concentration SiO2-rich noncrystalline Zr and Hf silicate alloys (2000)

Dielectric constants, k, of Zr(Hf) silicate alloy gate dielectrics obtained from analysis of capacitance–voltage curves of metal–oxide–semiconductor capacitors with 3–6 at. % Zr(Hf) are significantly larger than estimates of k based on linear extrapolations between SiO2 and compound silicates, Zr(Hf)SiO4. Analysis of infrared spectra of Zr silicate alloys with 3–16 at. % Zr indicates increases in the coordination of Zr to O atoms from 4 to approximately 8 with increasing Zr content. The major contributions to enhancements in k in these low Zr(Hf) content alloys are explained by a transverse infrared effective charge that scales inversely with increasing Zr–O bond coordination.
Estrogen regulates vesicle trafficking gene expression in EFF-3, EFM-19 and MCF-7 breast cancer cells. (2009)

Estrogens are critical mediators of breast tumorigenesis. This occurs via the action of estrogens on the estrogen receptor (ER), which regulates the transcriptome of breast cancer cells. Despite the long history of the search for estrogen-regulated genes in breast cancer, knowledge of the E2-regulated transcriptome and its effects is incomplete. We used Affymetrix GeneChips to profile the effects of estradiol on the expression of genes in EFF-3, EFM-19 and MCF-7 cells. In addition to many well-characterized estrogen-regulated genes, this identified a novel group of genes that have roles in vesicle trafficking, including exocytosis. Recent evidence in the literature supports a role for vesicle trafficking in tumorigenesis. We focused on five genes (SYTL5, RAB27B, SNX24, GALNT4 and SLC12A2/NKCC1/BSC2) and confirmed their estrogen-regulation using quantitative real-time PCR (qPCR). qPCR also demonstrated that these five genes were expressed in invasive breast carcinoma tissue. Immunohistochemistry showed expression of SYTL5 in cells of normal breast ductal epithelium, ductal carcinoma in-situ (DCIS) and invasive breast carcinoma. The results suggest that a significant effect of estrogens is to regulate the expression of genes that affect diverse aspects of vesicle trafficking including exocytosis.
CONCEPTIONS OF THE ABSURD (Book) (2002)

We have examined 41 cases of follicle centre cell lymphoma with fluorescent PCR of microsatellite repeats closely linked to or within six tumour suppressor gene loci (APC, DCC, P53, RB1, WT1 and NM23). These probes are highly informative with heterozygousity rates in the range of 57%-90%. In addition we have used four loci from chromosome 6 (D6S260, TNFa, D6S281 and D6S262) as control loci which are unlikely to be involved in the pathogenesis of lymphoma. Of 369 informative PCR reactions allele imbalance was identified in 38 (10%) and this was seen in 23 of the 41 cases. Looking at individual loci allele imbalance was seen in APC(1) 11%, APC(2) 12%, P53(1) 5%, P53 (2) 7%, WT1 5%, RB1 13%, DCC 18% and NM23 0%. This frequency of change was no different from that seen at the control loci D6S260 16%, TNFa 20%, D6S281 4% and D6S262 9%. In the indolent phase of germinal centre cell lymphoma there is therefore quite a high rate of allele imbalance at all loci but this is no higher in those loci linked to tumour suppressor genes.
The Effect of Epidural Versus General Anesthesia on Postoperative Pain and Analgesic Requirements in Patients Undergoing Radical Prostatectomy (1994)

In patients undergoing lower abdominal surgery, the neuraxial blockade and surgical anesthesia achieved by epidural local anesthetics was associated with decreased postoperative analgesic demands. Lower postoperative analgesic requirements in the EA group, when compared with both the EG and GA groups, indicate that: (1) EA patients had less postoperative pain, and (2) an efficient intraoperative blockade of noxious afferent signals to the central nervous system is fundamental in reducing postoperative pain.
Human DNA polymerases alpha and beta are able to incorporate anti-HIV deoxynucleotides into DNA. (1992)

Deoxynucleoside analogs, AZT and/or ddN, are the therapeutic agents currently utilized to inhibit the human immunodeficiency virus (HIV) reverse transcriptase. The effects of their anabolic products, AZT-triphosphate (AZT-TP) and ddCTP on human cellular DNA metabolic processes were studied using highly purified, structurally and enzymatically defined forms of the two major human host DNA polymerases, alpha and beta, and compared to those of the reverse transcriptase purified from HIV viron. Human DNA polymerase alpha during processive DNA synthesis is able to incorporate AZT-monophosphate (AZT-MP) but not ddCMP into DNA, causing chain termination. During its initial encounter with a primer terminus, polymerase alpha is able to incorporate both AZT-MP and ddCMP into DNA chains. Polymerase beta is able to incorporate AZT-MP and ddCMP into DNA, causing chain termination in both modes of DNA synthesis. Steady state kinetic analyses demonstrate that polymerase alpha inserts one AZT-MP molecule into DNA for every 2500 dTMP molecules incorporated. Polymerase beta incorporates ddCMP with efficiency nearly equal to that of dCMP. HIV reverse transcriptase prefers to incorporate AZT-MP and ddCMP rather than dTMP and dCMP, respectively. The findings described here raise the concern that the capability of the two major host DNA polymerases to incorporate AZT-MP or ddCMP into DNA might cause adverse side effects on human DNA metabolism and mutation in the genomes of patients under long term continuous treatment with AZT and ddC.
Isolation and kinetic properties of acetohydroxy acid isomeroreductase from spinach (Spinacia oleracea) chloroplasts overexpressed in Escherichia coli (1992)

Acetohydroxy acid isomeroreductase catalyses a two-step reaction, an alkyl migration and a NADPH-dependent reduction, in the assembly of the carbon skeletons of branched-chain amino acids. Detailed investigations of acetohydroxy acid isomeroreductase aimed at elucidating the biosynthetic pathway of branched-chain amino acids and at designing new inhibitors of the enzyme having herbicidal potency have so far been conducted with the enzymes isolated from bacteria. To gain more information on a plant system, the gene encoding the mature acetohydroxy acid isomeroreductase from spinach (Spinacia oleracea) leaf chloroplasts has been used to transform Escherichia coli cells and to overexpress the enzyme. A rapid protocol is described that allows the preparation of large quantities of pure spinach chloroplast acetohydroxy acid isomeroreductase. Kinetic and structural properties of the plant enzyme expressed in Escherichia coli are compared with those reported in our previous studies on the native enzymes purified from spinach chloroplasts and with those reported for the corresponding enzymes isolated from Escherichia coli and Salmonella typhimurium. Both the plant and the bacterial enzymes obey an ordered mechanism in which NADPH binds first, followed by substrate (either 2-acetolactate or 2-aceto-2-hydroxybutyrate). Inhibition studies employing an inactive substrate analogue, 2-hydroxy-2-methyl-3-oxopentanoate, showed, however, that the binding of 2-hydroxy-2-methyl-3-oxopentanoate and NADPH occurs randomly, suggestive of some flexibility of the plant enzyme active site. The observed preference of the enzyme for 2-aceto-2-hydroxybutyrate over 2-acetolactate is discussed with regard to the contribution of acetohydroxy acid isomeroreductase activity in the partitioning between isoleucine and valine biosyntheses. Moreover, the kinetic properties of the chloroplast enzyme support the notion that biosynthesis of branched-chain amino acids in plants is controlled by light. As judged by analytical-ultracentrifugation and gel-filtration analyses the overexpressed plant enzyme is a dimer of identical subunits.
Surfactants in Nano‐Emulsions (2005)

This chapter contains sections titled: Introduction Mechanism of Emulsification Methods of Emulsification and the Role of Surfactants Preparation of Nano-Emulsions Use of High Pressure Homogenizers Phase Inversion Temperature (PIT) Principle Steric Stabilization and the Role of the Adsorbed Layer Thickness Ostwald Ripening Practical Examples of Nano-Emulsions
Expression of a molecularly cloned human c-src oncogene by using a replication-competent retroviral vector. (1986)

We studied the expression of a molecularly cloned human c-src gene, c-src-1, localized on chromosome 20, whose coding region consists of 11 exons and spans a 19.5-kilobase (kb) distance. Using a replication-competent retroviral vector derived from molecularly cloned Rous sarcoma virus DNA (pSRA-2), we obtained two constructs: one (pSR-CS) carrying the unmodified human c-src coding sequence and another (pSR-CVS) with a chimeric gene formed between the human c-src gene and the carboxy-terminal 12-amino acid v-src-specific coding sequence. From chicken embryo fibroblasts transfected with these DNA constructs, infectious viruses designated as WO CS and WO CVS, respectively, were recovered. WO CS virus did not cause cell transformation, whereas WO CVS induced cell transformation. Analyses of the proviral DNAs indicated that all introns were spliced out such that the 19-kb inserts were converted to 1.7-kb cDNA forms. Analyses of src proteins in infected cells, using monoclonal antibody MAb327 against v-src protein, showed the following results. The CVS and CS src proteins were about 60 and 61 kilodaltons in size, respectively; the specific protein kinase activity assayed in vitro of the CVS src protein was about 20-fold higher than that of the CS src protein and comparable to that of the v-src protein; the transforming CVS src protein reacted to an antibody against a v-src-specific peptide, whereas the CS src protein did not. These results indicate that the human c-src gene has a potential transforming ability and suggest that the v-src-specific sequence played an important role in the generation of Rous sarcoma virus.
Spiking neural network training using evolutionary algorithms (2006)

Networks of spiking neurons can perform complex non-linear computations in fast temporal coding just as well as rate coded networks. These networks differ from previous models in that spiking neurons communicate information by the timing, rather than the rate, of spikes. To apply spiking neural networks on particular tasks, a learning process is required. Most existing training algorithms are based on unsupervised Hebbian learning. In this paper, we investigate the performance of the parallel differential evolution algorithm, as a supervised training algorithm for spiking neural networks. The approach was successfully tested on well-known and widely used classification problems.
Immobilized Clostridium acetobutylicum P262 Mutants for Solvent Production (1985)

The production of acetone, butanol, and ethanol by two immobilized, sporulation-deficient (spo) Clostridium acetobutylicum P262 mutants which were held in the solventogenic phase was investigated. The spoA2 mutant, which was an early-sporulation mutant and did not form a forespore septum, produced higher solvent yields than did the spoB mutant which was a late-sporulation mutant and was blocked at a stage after forespore septum formation. The spoA2 mutant was also granulose and capsule negative. In a conventional batch fermentation, the wild-type strain produced 15.44 g of solvents per liter after 50 h at a productivity of 7.41 g of solvents per liter per day. The spoA2 mutant produced 15.42 g of solvents per liter at a productivity of 72.4 g of solvents per liter per day, with a retention time of 2.4 h in a continuous immobilized cell system employing a fluidized bed reactor. This represents a major advance, since the immobilization of wild-type cells showed similar increases in productivity but a ca. fivefold reduction in final product concentrations.
Dielectrophoretic focusing of particles in a microchannel constriction using DC‐biased AC flectric fields (2009)

This paper presents a fundamental study of particle electrokinetic focusing in a single microchannel constriction. Through both experiments and simulations, we demonstrate that such dielectrophoresis-induced particle focusing can be implemented in a much smaller magnitude of DC-biased AC electric fields (10 kV/m in total) as compared to pure DC electric fields (up to 100 kV/m). This is attributed to the increase in the ratio of cross-stream particle dielectrophoretic velocity to streamwise electrokinetic velocity as only the DC field component contributes to the latter. The effects of the 1 kHz frequency AC to DC electric field ratio on particle trajectories and velocity variations through the microchannel constriction are also examined, which are found to agree with the simulation results.