gebhart/patrepeval huggingface dataset:
Inhibition of beta-adrenergic receptor kinase prevents rapid homologous desensitization of beta 2-adrenergic receptors. (1989)

Homologous (agonist-specific) desensitization of beta-adrenergic receptors (beta ARs) is accompanied by and appears to require phosphorylation of the receptors. We have recently described a novel protein kinase, beta AR kinase, which phosphorylates beta ARs in vitro in an agonist-dependent manner. This kinase is inhibited by two classes of compounds, polyanions and synthetic peptides derived from the beta 2-adrenergic receptor (beta 2AR). In this report we describe the effects of these inhibitors on the process of homologous desensitization induced by the beta-adrenergic agonist isoproterenol. Permeabilization of human epidermoid carcinoma A431 cells with digitonin was used to permit access of the charged inhibitors to the cytosol; this procedure did not interfere with the pattern of isoproterenol-induced homologous desensitization of beta 2AR-stimulated adenylyl cyclase. Inhibitors of beta AR kinase markedly inhibited homologous desensitization of beta 2ARs in the permeabilized cells. Inhibition of desensitization by heparin, the most potent of the polyanion inhibitors of beta AR kinase, occurred over the same concentration range (5-50 nM) as inhibition of purified beta AR kinase assessed in a reconstituted system. Inhibition of desensitization by heparin was accompanied by a marked reduction of receptor phosphorylation in the permeabilized cells. Whereas inhibitors of beta AR kinase inhibited homologous desensitization, inhibitors of protein kinase C and of cyclic-nucleotide-dependent protein kinases were ineffective. These data establish that phosphorylation of beta ARs by beta AR kinase is an essential step in homologous desensitization of the receptors. They further suggest a potential therapeutic value of inhibitors of beta AR kinase in inhibiting agonist-induced desensitization.
Kinetics of solid phase epitaxy in thick amorphous Si layers formed by MeV ion implantation (1990)

The kinetics of solid phase epitaxy (SPE) have been measured in MeV ion-implanted amorphous Si layers up to 5 μm thick. Epitaxial crystallization in these layers occurs at a constant rate throughout the entire film, without loss of interface planarity or competition from random nucleation or twin formation. The activation energy for SPE in thick layers is found to be 2.70 eV, in excellent agreement with the value determined previously in much thinner films. The SPE kinetics are shown not to depend on the implant dose for doses up to 1000 times the threshold for amorphization. The presence of water vapor in the annealing ambient during SPE results in the indiffusion of hydrogen and a concomitant reduction of the SPE growth rate at distances as great as 2 μm from the surface. This effect may have important implications for the development of a microscopic model of the SPE process in silicon.
Concentration and purification by magnetic separation of the erythrocytic stages of all human Plasmodium species (2008)

The magnetic removal of non-parasitized red blood cells (in vivo and in vitro) using magnetic columns (MACS) was evaluated. This easy-to-use technique enriched schizonts and gametocytes from Plasmodium falciparum in vitro cultures with a very high degree of purity. In addition, all haemozoin-containing stages (schizonts and/or gametocytes) from the peripheral blood of infected patients could be concentrated using this method. This method is particularly useful for the concentration of non-falciparum species, which do not grow in culture and are otherwise difficult to obtain in large amounts.
Overexpression of the Wilms' tumor gene WT1 in pancreatic ductal adenocarcinoma (2004)

The expression of the Wilms' tumor gene WT1 was examined by immunohistochemistry in 40 cases of pancreatic ductal adenocarcinoma. WT1 protein was expressed in 30 (75%) of the 40 pancreatic ductal adenocarcinomas, but not in the remaining 10 (25%). In normal pancreatic ductal cells, WT1 protein was undetectable. No correlations between WT1 expression and clinicopathological parameters such as age, sex, T or N stage, tumor location, and tumor differentiation were observed. Treatment with WT1 antisense oligomers significantly inhibited the growth of five human pancreatic cancer cell lines, PSN1, MiaPaCa2, ASPC1, BxPC3, and PCI6, expressing the WT1 gene. These results indicate an important role of the WT1 gene in the tumorigenesis of pancreatic ductal adenocarcinoma expressing WT1 and provide a rationale for new treatment strategies to treat pancreatic ductal adenocarcinoma by targeting the WT1 gene and its product.
Study on cell characteristics of PRAM using the phase-change simulation (2003)

In this paper, we present a new simulation methodology for analyzing cell characteristics of the chalcogenide based phase-change device, PRAM (Phase-change Random Access Memory), which is the future-generation non-volatile memory. Using the new simulation methodology, we analyze the effect of process variation, which is the most sensitive factor to operate the cell of PRAM.
Impedance Analyzer for in vivo Electroporation Studies (2006)

Electroporation, the permeabilization of the cell membrane with electrical pulses, is being used for in vivo gene therapy, drug therapy and minimally invasive tissue ablation. Applying electrical pulses across cells can have a variety of outcomes; from no effect to reversible electroporation to irreversible electroporation. For reliable in vivo use of electroporation it is important to have real time feedback on the outcome of the application of the electrical pulse. Recently, it has been proposed that measuring the electrical properties of electroporated tissues in temporal relation to the applied pulses could provide this feedback. To generate fundamental data on the in vivo electrical properties of electroporated tissues we have developed a fast spectroscopic impedance analyzer that measures electrical properties of tissues in vivo in conjunction with commercial electroporation pulse generators. Here we describe the apparatus and illustrate its use with an experiment on reversible electroporation in a rat liver.
Courtroom Observation and Applied Litigation Research: A Case History of Jury Decision Making (1993)

Quantitative research has dom inated applied litigation research, but it seem s to lack the flexibility needed to link pretrial research to ongoing courtroom events. Participant observation is a methodology which seems more suitable for studying the dynamic environment of a trial. A 6-day civil trial is used to evaluate participant observation reports against pretrial survey analysis and trial simulations. The objective is to show how different methodological approaches converge in the frame of reference which reflects the actual verdict reached in tria l. Litigation research is a relatively new field of social science application. The most useful methodological approaches to study ongoing litigation are still under development. Quantitative designs have dominated this field to date and typically are used for jury selection (Frederick, 1984; Penrod &amp;amp; Linz, 1986). Quantitative techniques, such as secondary analysis of survey data, have been employed to help create checklist scales to evaluate potential jurors for prejudicial tendencies during voir dire (Abbott, 1987). Another purpose of quantitative techniques, which is used less often, is to focus strategic themes and arguments for trial. Nonetheless, quantitative designs have been strongly criticized (Saks, 1976), in large part
Effects of nicotine on periodontal ligament fibroblasts in vitro (1999)

Cigarette smoking is associated with increased incidence of periodontal disease and poor response to therapy. In the present study, we examined the effects of nicotine on several functions of periodontal ligament fibroblasts (PDLF): proliferation, attachment, alkaline phosphatase production and chemotaxis. Nicotine concentrations varying from 5 ng/ml to 250 microg/ml were tested. Proliferation of cells was studied by the incorporation of 3H-thymidine, and a dose-dependent inhibition was observed with concentrations > or =100 ng/ml. Similar results were observed when studying the attachment of the cells on plastic surfaces, using a colorimetric method. The inhibition of attachment was even more evident after 6 h incubation of the cells with nicotine. The activity of alkaline phosphatase, as determined with the substrate p-nitrophenyl phosphate, in both conditioned medium (CM) and cellular extract (CE), was also significantly decreased in a concentration-related fashion. Finally, the chemotaxis of PDLE as examined by a modification of the Boyden's blind-well chamber technique, was inhibited in a dose-dependent manner. The degree of inhibition varied from 15% with the lowest concentration of nicotine (50 ng/ml), to almost 90% with the highest (5 microg/ml). The results show that nicotine can have direct adverse effects on various functions of the periodontal cells.
Hypoglossal-Nerve Stimulation for Obstructive Sleep Apnea (2014)

Obstructive sleep apnea has well-established neurocognitive and cardiovascular sequelae.1 Conservative estimates suggest that approximately 13% of men and 6% of women in North America have clinically important obstructive sleep apnea.2 Despite the transformative benefits in some patients who receive therapy with continuous positive airway pressure (CPAP),3 many patients remain inadequately treated owing to inconsistent levels of adherence to existing therapies. Thus, further research is required to allow new therapeutic options to evolve.Traditionally, obstructive sleep apnea has been defined by anatomical compromise in which soft tissues and craniofacial structures around the pharyngeal airway lead to increased airway collapsibility.4 Because of . . .
Trk Receptors Function As Rapid Retrograde Signal Carriers in the Adult Nervous System (1997)

During development target-derived neurotrophins promote the survival of neurons. However, mature neurons no longer depend on the target for survival. Do target-derived neurotrophins retain retrograde signaling functions in mature neurons, and, if so, how are they executed? We addressed this question by using a phosphotyrosine-directed antibody to locate activated Trk receptors in adult rat sciatic nerve. We show that catalytically active Trk receptors are located within the axon of adult rat sciatic nerve and that they are distributed throughout the length of the axons. These catalytically active receptors are phosphorylated on tyrosine at a position that couples them to the signal-generating proteins Ras and PI3 kinase. Neurotrophin applied at sciatic nerve terminals increases both catalytic activity and phosphorylation state of Trk receptors at distant points within the axons. Trk activation initiated at the nerve terminals propagates through the axon toward the nerve cell body at an initial rate that exceeds that of conventional vesicular transport. However, our data suggest that this rapid signal is nevertheless vesicle-associated. Thus, in mature nerves, activated Trk receptors function as rapid retrograde signal carriers to execute remote responses to target-derived neurotrophins.
Real-time observation of DNA target interrogation and product release by the RNA-guided endonuclease CRISPR Cpf1 (Cas12a) (2018)

CRISPR-Cas9, which imparts adaptive immunity against foreign genomic invaders in certain prokaryotes, has been repurposed for genome-engineering applications. More recently, another RNA-guided CRISPR endonuclease called Cpf1 (also known as Cas12a) was identified and is also being repurposed. Little is known about the kinetics and mechanism of Cpf1 DNA interaction and how sequence mismatches between the DNA target and guide-RNA influence this interaction. We used single-molecule fluorescence analysis and biochemical assays to characterize DNA interrogation, cleavage, and product release by three Cpf1 orthologs. Our Cpf1 data are consistent with the DNA interrogation mechanism proposed for Cas9. They both bind any DNA in search of protospacer-adjacent motif (PAM) sequences, verify the target sequence directionally from the PAM-proximal end, and rapidly reject any targets that lack a PAM or that are poorly matched with the guide-RNA. Unlike Cas9, which requires 9 bp for stable binding and ∼16 bp for cleavage, Cpf1 requires an ∼17-bp sequence match for both stable binding and cleavage. Unlike Cas9, which does not release the DNA cleavage products, Cpf1 rapidly releases the PAM-distal cleavage product, but not the PAM-proximal product. Solution pH, reducing conditions, and 5' guanine in guide-RNA differentially affected different Cpf1 orthologs. Our findings have important implications on Cpf1-based genome engineering and manipulation applications.
The formation of complexes between aza-derivatives of crown ethers and primary alkylammonium salts. Part 5. Chiral macrocyclic diamines (1979)

Syntheses of three types of chiral macrocyclic diamines, analogous to crown ethers, are described. The chirality of these systems is based, in one case, upon the plane of chirality of paracyclophane systems and, in the other two cases, upon the axis of chirality of bridged biphenyls. Two methods are described for the measurement of chiral selectivity in the formation of complexes between these chiral macrocyclic host molecules and chiral guest primary alkylammonium salts. Both methods use n.m.r. Spectrometry, a single-phase system, a racemic chiral host and (R)- and (RS)-guest salts. The first method is suitable for both optically labile and optically stable hosts and the second method is only suitable for optically labile host species.
Principles of thick film materials formulation (1975)

The composition of thick film pastes, the processes which occur during firing, and the structure of the resulting film are described and problems encountered in the development of these materials are discussed. The methods which have been used to produce conductors with high conductivity and adhesion, resistors with a wide range of value, insulants suitable for multilayer structures, and printed capacitors with the maximum possible capacitance per unit area are outlined, with emphasis on some new developments.
Intolerance to neuroleptic drugs: the art of avoiding extrapyramidal syndromes (1995)

Akathisia, dystonia, dyskinesia and parkinsonism, the four main categories of neuroleptic-induced extrapyramidal syndromes (EPS), represent major disadvantages in antipsychotic therapy. In vulnerable patients, acute EPS may progress into potentially irreversible forms such as tardive dystonia and tardive dyskinesia. In the psychiatric clinic, these EPS are often insufficiently recognised or permitted to exist without treatment. In order to ensure a better EPS diagnosis, a simple examination procedure is described. EPS rating scales may serve as an aid in this process. Guidelines are given to prevent and treat EPS. Thus, EPS are best prevented by a course of neuroleptic medication involving as little antidopaminergic D(2) effect as possible, including the use of the lowest effective dose )sometimes obtained by addition of a benzodiazepine or carbamazepine) and with antipsychotic drugs which produce low D(2) receptor blockade. Treating EPS also consists of using the lowest effective dose and antipsychotics with a low D(2) dopamine receptor occupancy. At present, clozapine is the only drug that produces antipsychotic benefits at doses that cause far less D(2) receptor antagonism in the basal ganglia of the brain than that seen with standard neuroleptics; however, newer drugs, such as olanzepine, seroquel and sertindole, are on the way.
MICRO-ELECTRO-MECHANICAL-SYSTEMS (MEMS) AND FLUID FLOWS (1998)

▪ Abstract The micromachining technology that emerged in the late 1980s can provide micron-sized sensors and actuators. These micro transducers are able to be integrated with signal conditioning and processing circuitry to form micro-electro-mechanical-systems (MEMS) that can perform real-time distributed control. This capability opens up a new territory for flow control research. On the other hand, surface effects dominate the fluid flowing through these miniature mechanical devices because of the large surface-to-volume ratio in micron-scale configurations. We need to reexamine the surface forces in the momentum equation. Owing to their smallness, gas flows experience large Knudsen numbers, and therefore boundary conditions need to be modified. Besides being an enabling technology, MEMS also provide many challenges for fundamental flow-science research.
Synthesis and quantitative structure-activity relationships of diclofenac analogs (1990)

The synthesis of a series of 2-anilinophenylacetic acids, close analogues of diclofenac, is described. These compounds were tested in two models used for evaluating the activity of nonsteroidal antiinflammatory drugs (NSAID's), inhibition of cyclooxygenase enzyme activity in vitro, and adjuvant-induced arthritis (AdA) in rats. Statistically significant correlations were found between the inhibitory activities of the compounds in these two models, indicating that cyclooxygenase inhibition seems to be the underlying mechanism for the antiinflammatory activity of these compounds. Quantitative structure-activity relationship (QSAR) analysis revealed that the crucial parameters for activity in both models were the lipophilicity and the angle of twist between the two phenyl rings. Optimal activities were associated with halogen or alkyl substituents in both ortho positions of the anilino ring. Compounds with OH groups in addition to two ortho substituents or compounds with only one or no ortho substituents were less active.
Concurrent and independent genetic alterations in the stromal and epithelial cells of mammary carcinoma: implications for tumorigenesis. (2000)

The high frequency of loss of heterozygosity (LOH) in epithelial cells of mammary ductal carcinoma in situ (DCIS) and IDC is a well known phenomenon, whereas the genetic abnormalities in the mammary stroma and its influence on the epithelial component have not been sufficiently studied. Using the PCR, we examined DNA extracts from microdissected stromal and epithelial tissues of 11 breast samples containing DCIS, including five cases associated with IDC. In each case, the mesenchymal tissue consisting of normal-appearing stroma at a distance from DCIS and IDC or stroma close to either DCIS or IDC was manually microdissected. Epithelial cells from morphologically clear-cut normal ducts and lobules, DCIS, and IDC were also microdissected. Twelve polymorphic DNA markers were tested to identify possible genetic alterations in the mesenchymal and epithelial cells on chromosomes 2p, 3p, 11q, 16q, and 17q. Samples from bilateral reduction mammoplasty from 10 women without any clinical, radiological, or pathological abnormalities were also selected as a control (reduction mammoplasty group). Whereas most cases (8/11, 73%) displayed at least one identical LOH in both epithelial and mesenchymal components, LOH at several loci was noted exclusively in stromal cells. The most frequent genetic alterations in the mesenchymal cells were at chromosomes 17q24, 16q23.1-24.2, 3p14.2, and 11q21-23.2, in 87.5, 62, 60, and 45% of informative cases, respectively. The LOH frequency in the stroma close to cancer ranged from 10 to 66.5% for DCIS and from 20 to 75% of informative cases for IDC. Furthermore, 10 of the 12 polymorphic markers revealed LOH in the stroma at a distance, ranging from 11 to 57% of informative cases. None of the control cases (women without any breast disease) revealed LOH either in the epithelial or in the stromal components. Our findings strongly support the concept of stromal-epithelial interaction in the development and progression of mammary neoplasia. Furthermore, this study suggests that genetic alterations in the stromal cells may precede genotypic changes in the epithelial cells. At least in some cases, the mammary stroma in DCIS or IDC apparently represents a neoplastic interactive component rather than a reactive response to the carcinoma. The frequent allelic loss (LOH) in the mammary stroma, identified in our study, may explain some of the fibroblastic abnormalities previously observed in patients with breast carcinoma or a variety of cancer-associated hereditary diseases. We conclude that the mammary stroma may play a key role in inducing neoplastic transformation of epithelial cells, recapitulating its role in normal mammary duct development.
A σ54-dependent PTS permease of the mannose family is responsible for sensitivity of Listeria monocytogenes to mesentericin Y105 (2001)

Sensitivity of Listeria monocytogenes to the bacteriocin mesentericin Y105 was previously shown to be dependent on the sigma(54) subunit of the RNA polymerase. This points towards expression of particular sigma(54)-dependent genes. The present study describes first, ManR, a new sigma(54)-associated activator, and second, Ell(t)(Man), a new sigma(54)-dependent PTS permease of the mannose family, both involved in sensitivity to mesentericin Y105, since interruption of their corresponding genes led to resistance of L. monocytogenes EGDe. Ell(t)(Man) is likely composed of three subunits encoded by the mpt operon (mptA, mptC and mptD genes). Interruption of either the proximal (mptA) or distal (mptD) gene led to resistance, supporting results obtained in Enterococcus faecalis. Accordingly, such PTS permeases of the mannose family should be involved in sensitivity of different target strains to mesentericin Y105. In L. monocytogenes, expression of the mpt operon is shown to be controlled by sigma(54) and ManR and to be induced by both glucose and mannose. The latter result indicates that these sugars are transported by the Ell(t)(Man) permease. Moreover, these sugars correlatively induce sensitivity of L. monocytogenes to mesentericin Y105, strongly favouring the primary role of Ell(t)(Man). MptD, a membrane subunit of Ell(t)(Man), presents an additional domain compared to most IID(Man) subunits described in data banks. An in-frame deletion of this domain in mptD led to resistance of L. monocytogenes, showing its connection with sensitivity and suggesting that it could be directly involved in the recognition of the target cell by mesentericin Y105. Taken together, the results of this work demonstrate that Ell(t)(Man) is prominent in sensitivity to mesentericin Y105 and could be a receptor for subclass IIa bacteriocins.
Effect of Varying Fibrinogen and Hematocrit Concentrations on Magnetic Resonance Relaxation Times of Thrombus (1992)

Both extracellular (fibrinogen) and cellular (erythrocyte concentration) factors are significant determinants of thrombus T1 and T2 relaxation times.