gebhart/patrepeval huggingface dataset:
Targeted Disruption of the CXCL12/CXCR4 Axis Inhibits Osteolysis in a Murine Model of Myeloma-Associated Bone Loss (2009)

The plasma cell (PC) malignancy, multiple myeloma (MM), is unique among hematological malignancies in its capacity to cause osteoclast (OC)-mediated skeletal destruction. We have previously shown that elevated plasma levels of PC-derived CXCL12 are associated with presence of X-ray detectable osteolytic lesions in MM patients. To further investigate this relationship, plasma levels of CXCL12 and betaCrossLaps, a marker of bone loss, were measured. A strong correlation between levels of CXCL12 and OC-mediated bone resorption was identified. To confirm the OC-activating potential of MM PC-derived CXCL12 in vivo, we established a model of MM-mediated focal osteolysis, wherein MM PC lines, such as RPMI-8226, were injected into the tibias of nude mice. Implanting RPMI-8226 gave rise to osteolytic lesions proximal to the tumor, resulting in a 5% decrease in bone volume (BV) compared with vehicle control. Importantly, bone loss was significantly inhibited with systemic administration of the CXCL12/CXCR4 antagonist T140. Furthermore, implanting CXCL12-overexpressing RPMI-8226 cells resulted in a 13% decrease in BV and was associated with increased OC recruitment proximal to the tumor, increased serum matrix metalloproteinase activity, and increased levels of collagen I degradation products. These findings confirm our hypothesis that MM PC-derived CXCL12 stimulates the recruitment and activity of OC, thereby contributing to the formation of MM osteolytic lesions.
The muscle slice—A new preparation for the characterization of β‐adrenergic binding in fast‐ and slow‐twitch skeletal muscle (1986)

A new procedure is presented that characterizes the specific binding of the beta-adrenergic antagonist, [3H]CGP-12177, to thick (1 mm) slices from fast-twitch [extensor digitorum longus (EDL)] and slow-twitch (soleus) mouse skeletal muscle. Binding is reversible, saturable, stereospecific, of high affinity, and subject to agonist-induced desensitization, indicating that it is to beta-adrenoreceptors and not to other sites. In both muscles, the majority of specific binding is to the beta 2-receptor subtype. Bmax is approximately twice as high in the soleus (5.64 +/- 0.52 fmol/mg wet weight) as in the EDL (2.66 +/- 0.29 fmol/mg wet weight) (P less than 0.05), whereas affinity is higher in the fast-twitch (Kd = 0.30 +/- 0.08 nM) than the slow-twitch muscle (Kd = 0.45 +/- 0.08 nM). The minimal tissue disruption associated with this procedure, as well as its speed, simplicity and relatively low cost, suggest that the slice preparation may prove to be invaluable for the future study of beta-adrenergic receptor binding and associated responses in skeletal muscle.
Structure and Sequence Determinants Required for the RNA Editing of ADAR2 Substrates (2004)

ADAR2 is a double-stranded RNA-specific adenosine deaminase involved in the editing of mammalian RNAs by the site-specific conversion of adenosine to inosine. We have demonstrated previously that ADAR2 can modify its own pre-mRNA, leading to the creation of a proximal 3'-splice junction containing a non-canonical adenosine-inosine (A-I) dinucleotide. Alternative splicing to this proximal acceptor shifts the reading frame of the mature mRNA transcript, resulting in the loss of functional ADAR2 expression. Both evolutionary sequence conservation and mutational analysis support the existence of an extended RNA duplex within the ADAR2 pre-mRNA formed by base-pairing interactions between regions approximately 1.3-kilobases apart in intron 4 and exon 5. Characterization of ADAR2 pre-mRNA transcripts isolated from adult rat brain identified 16 editing sites within this duplex region, and sites preferentially modified by ADAR1 and ADAR2 have been defined using both tissue culture and in vitro editing systems. Statistical analysis of nucleotide sequences surrounding edited and non-edited adenosine residues have identified a nucleotide sequence bias correlating with ADAR2 site preference and editing efficiency. Among a mixed population of ADAR substrates, ADAR2 preferentially favors its own transcript, yet mutation of a poor substrate to conform to the defined nucleotide bias increases the ability of that substrate to be modified by ADAR2. These data suggest that both sequence and structural elements are required to define adenosine moieties targeted for specific ADAR2-mediated deamination.
p130Cas, a Substrate Associated with v-Src and v-Crk, Localizes to Focal Adhesions and Binds to Focal Adhesion Kinase (1996)

p130Cas (rk ssociated ubstrate) has the structural characteristics of an adapter protein, containing multiple consensus SH2 binding sites, an SH3 domain, and a proline-rich domain. The structure of p130Cas suggests that it may act to provide a framework for protein-protein interactions; however, as yet, its functional role in cells is unknown. In this report we show that p130Cas is localized to focal adhesions. We demonstrate that p130Cas associates both in vitro and in vivo with pp125FAK (ocal dhesion inase), a kinase implicated in signaling by the integrin family of cell adhesion receptors. p130Cas also associates with pp41/43FRNK (pp125FAK-related, non-kinase), an autonomously expressed form of pp125FAK composed of only the C-terminal noncatalytic domain. We show that the association of p130Cas with pp125Fak and pp41/43FRNK is direct, and is mediated by the binding of the SH3 domain of p130Cas to a proline-rich sequence present in both the C terminus of pp125FAK and in pp41/43FRNK. In agreement with recent studies we show that p130Cas is tyrosine-phosphorylated upon integrin mediated cell adhesion. The association of p130Cas with pp125FAK, a kinase which is activated upon cell adhesion, is likely to be functionally important in integrin mediated signal transduction. p130Cas (rk ssociated ubstrate) has the structural characteristics of an adapter protein, containing multiple consensus SH2 binding sites, an SH3 domain, and a proline-rich domain. The structure of p130Cas suggests that it may act to provide a framework for protein-protein interactions; however, as yet, its functional role in cells is unknown. In this report we show that p130Cas is localized to focal adhesions. We demonstrate that p130Cas associates both in vitro and in vivo with pp125FAK (ocal dhesion inase), a kinase implicated in signaling by the integrin family of cell adhesion receptors. p130Cas also associates with pp41/43FRNK (pp125FAK-related, non-kinase), an autonomously expressed form of pp125FAK composed of only the C-terminal noncatalytic domain. We show that the association of p130Cas with pp125Fak and pp41/43FRNK is direct, and is mediated by the binding of the SH3 domain of p130Cas to a proline-rich sequence present in both the C terminus of pp125FAK and in pp41/43FRNK. In agreement with recent studies we show that p130Cas is tyrosine-phosphorylated upon integrin mediated cell adhesion. The association of p130Cas with pp125FAK, a kinase which is activated upon cell adhesion, is likely to be functionally important in integrin mediated signal transduction.
Construction of recombinant plasmids containing rat muscle actin and myosin light chain DNA sequences. (1980)

The construction and partial characterization of recombinant bacterial plasmids carrying DNA sequences that hybridize with rat skeletal muscle actin and a myosin light chain mRNA is described. DNA of one clone hybridizes specifically with the muscle-specific alpha-actin mRNA. Three plasmid clones contain DNA inserts that hybridize with muscle as well as with nonmuscle actin mRNA. A fifth plasmid contains sequences complementary to mRNA coding for myosin light chain 2. DNA of this plasmid hybridizes specifically with RNA extracted from muscle and differentiated muscle cultures but not with RNA extracted from proliferating mononucleated myogenic cells.
Reconfigurable Data Processing for Clouds (2011)

Reconfigurable computing in the cloud helps to solve many practical problems relating to scaling out data-centers where computation is limited by energy consumption or latency. However, for reconfigurable computing in the cloud to become practical several research challenges have to be addressed. This paper identifies some of the perquisites for reconfigurable computing systems in the cloud and picks out several scenarios made possible with immense cloud-based computing capability.
Tachykinin Receptors as Therapeutic Targets in Stress-Related Disorders (2009)

The first report demonstrating the therapeutic efficacy of an orally applied neurokinin-1 (NK1) receptor antagonist in depression was published 10 years ago. Although there were difficulties to reproduce this particular finding, a huge amount of data has been published since this time, supporting the potential therapeutic value of various tachykinin ligands as promising novel tools for the management of stress-related disorders including anxiety disorders, schizophrenia and depression. The present review summarizes evidence derived from anatomical, neurochemical, pharmacological and behavioral studies demonstrating the localization of tachykinin neuropeptides including substance P (SP), neurokinin A, neurokinin B and their receptors (NK1, NK2, NK3) in brain areas known to be implicated in stress-mechanisms, mood/anxiety regulation and emotion-processing; their role as neurotransmitters and/or neuromodulators within these structures and their interactions with other neurotransmitter systems including dopamine, noradrenaline and serotonin (5-hydroxytryptamine, 5-HT). Finally, there is clear functional evidence from animal and human studies that interference with tachykinin transmission can modulate emotional behavior. Based on these findings and on evidence of upregulated tachykinin transmission in individuals suffering from stress-related disorders, several diverse tachykinin receptor antagonists, as well as compounds with combined antagonist profile have been developed and are currently under clinical investigation revealing evidence for anxiolytic, antidepressant and antipsychotic efficacy, seemingly characterized by a low side effect profile. However, substantial work remains to be done to clarify the precise mechanism of action of these compounds, as well as the potential of combining them with established and experimental therapies in order to boost efficacy.
Functional optimization for fair surface design (1992)

article Free Access Share on Functional optimization for fair surface design Authors: Henry P. Moreton Computer Science Division, University of California, Berkeley Computer Science Division, University of California, BerkeleyView Profile , Carlo H. Séquin Computer Science Division, University of California, Berkeley Computer Science Division, University of California, BerkeleyView Profile Authors Info & Claims ACM SIGGRAPH Computer GraphicsVolume 26Issue 2July 1992 pp 167–176https://doi.org/10.1145/142920.134035Published:01 July 1992Publication History 245citation2,152DownloadsMetricsTotal Citations245Total Downloads2,152Last 12 Months140Last 6 weeks14 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Reduced virulence of a Listeria monocytogenes phospholipase-deficient mutant obtained by transposon insertion into the zinc metalloprotease gene (1992)

A phospholipase-deficient mutant, termed JL762, was obtained from a virulent strain of Listeria monocytogenes by screening a bank of 5,000 Tn1545 transposon-induced mutants on 2.5% egg yolk brain heart infusion agar. As previously shown (J. Mengaud, C. Geoffroy, and P. Cossart, Infect. Immun. 59:1043-1049, 1991), the transposon insertion took place inside the gene mpl, which encodes a zinc metalloprotease. By Western blot (immunoblot) analysis, we showed that loss of phospholipase activity was associated with loss of a 29-kDa zinc-dependent phosphatidylcholine-phospholipase C (PC-PLC) in culture supernatant of JL762 and of EGD-SmR incubated with ion chelator. As the parental strain, JL762 still produced in supernatants approximately 33-kDa proteins antigenically closely related to the 29-kDa PC-PLC. These results strongly suggest that the zinc metalloprotease of L. monocytogenes might play a role in the maturation of the 29-kDa PC-PLC. Although the uptake and the intracellular growth of bacteria were not affected in vitro, we found that the virulence of mutant JL762 was strongly impaired in the mouse.
[Sacral root neuromodulation for the treatment of urinary incontinence reported to detrusor hyperactivity]. (2003)

Neuromodulation strongly ameliorates approximately a third of all the patients with urge urinary incontinence due to detrusor hyperactivity. New technical improvements should lead to better results in the future.
Low‐dose anti‐CD20 veltuzumab given intravenously or subcutaneously is active in relapsed immune thrombocytopenia: a phase I study (2013)

Low doses of the humanized anti-CD20 monoclonal antibody, veltuzumab, were evaluated in 41 patients with immune thrombocytopenia (ITP), including 9 with ITP ≤1 year duration previously treated with steroids and/or immunoglobulins, and 32 with ITP >1 year and additional prior therapies. They received two doses of 80-320 mg veltuzumab 2 weeks apart, initially by intravenous (IV) infusion (N = 7), or later by subcutaneous (SC) injections (N = 34), with only one Grade 3 infusion reaction and no other safety issues. Thirty-eight response-assessable patients had 21 (55%) objective responses (platelet count ≥30 × 10(9) /l and ≥2 × baseline), including 11 (29%) complete responses (CRs) (platelet count ≥100 × 10(9) /l). Responses (including CRs) occurred with both IV and SC administration, at all veltuzumab dose levels, and regardless of ITP duration. Responders with ITP ≤1 year had a longer median time to relapse (14·4 months) than those with ITP >1 year (5·8 months). Three patients have maintained a response for up to 4·3 years. SC injections resulted in delayed and lower peak serum levels of veltuzumab, but B-cell depletion occurred after first administration even at the lowest doses. Eight patients, including 6 responders, developed anti-veltuzumab antibodies following treatment (human anti-veltuzumab antibody, 19·5%). Low-dose SC veltuzumab appears convenient, well-tolerated, and with promising clinical activity in relapsed ITP.(Clinicaltrials.gov identifier: NCT00547066.).
Differential cytotoxicity of novel somatostatin and dopamine chimeric compounds on bronchopulmonary and small intestinal neuroendocrine tumor cell lines (2008)

The different responses of each individual cell line suggested that NETs from different locations arising from different neuroendocrine cells may require cell-specific antiproliferative agents based on the unique receptor profile of individual lesions.
Cleavage of nucleolin and AgNOR proteins during apoptosis induced by anticancer drugs in human salivary gland cells (2005)

The present results indicate that alternations of nucleolin and AgNOR proteins are associated with the induction of DNA fragmentation and the final active phase of apoptosis induced by anticancer drugs in malignant salivary gland cells.
Influence of phosphatidylglycerol on the uptake of liposomes by alveolar cells and on lung function (2005)

The effect of phosphatidylglycerol on the uptake of surfactant-like liposomes by alveolar type II cells and alveolar macrophages as well as the effect on endogenous surfactant function was studied in vivo. Healthy ventilated rats were intratracheally instilled with fluorescent labeled liposomes with different concentrations of phosphatidylglycerol. Lung function was determined by monitoring arterial oxygenation and, at the end of the experiment, by recording static pressure-volume curves. In addition, alveolar cells were isolated, and cell-associated fluorescence was determined using flow cytometry. The results show that, in the presence of cofactors (Ca(2+), Mg(2+)), phosphatidylglycerol stimulates the uptake by alveolar macrophages but hardly affects the uptake by alveolar type II cells. High concentrations of phosphatidylglycerol reduce the number of alveolar macrophages in the alveolar space and deteriorate lung function. On the other hand, the presence of cofactors protects the lung against the negative effects of phosphatidylglycerol on endogenous surfactant and alveolar macrophages. This study indicates that the phosphatidylglycerol concentration may play a fundamental role in the surfactant function and metabolism depending on the presence of so-called cofactors like calcium and magnesium; further study is needed to clarify the mechanisms involved.
A method for building self-folding machines (2014)

Origami can turn a sheet of paper into complex three-dimensional shapes, and similar folding techniques can produce structures and mechanisms. To demonstrate the application of these techniques to the fabrication of machines, we developed a crawling robot that folds itself. The robot starts as a flat sheet with embedded electronics, and transforms autonomously into a functional machine. To accomplish this, we developed shape-memory composites that fold themselves along embedded hinges. We used these composites to recreate fundamental folded patterns, derived from computational origami, that can be extrapolated to a wide range of geometries and mechanisms. This origami-inspired robot can fold itself in 4 minutes and walk away without human intervention, demonstrating the potential both for complex self-folding machines and autonomous, self-controlled assembly.
Reduction of CO[sub 2] to Ethylene at Three-Phase Interface Effects of Electrode Substrate and Catalytic Coating (2005)

Effects of electrode substrate and catalytic coating on the electrochemical reduction of to ethylene at a three-phase interface have been investigated and the reduction scheme examined on the basis of the results of in situ Fourier transform infrared (FTIR) studies. The electrolysis of at a negative constant potential is carried out with copper-, silver-, Monel metal-, and stainless-mesh electrodes in a concentrated halide solution, and the generation of is not observed at all except on a pure Cu electrode. However, the fixation of copper(I) halide onto the other three substrates leads to the formation of with considerable current efficiencies, and it is demonstrated that copper(I) halide works as an active catalyst for the selective conversion of to independently of the nature of substrate. The following scheme is proposed for the electrochemical reduction of to based on the in situ FTIR spectra: is first reduced to carboxylic acid by one-electron reaction, the "side-on" type intermediate is then formed by the protonation, C–O bond cleavages, and C–C bond formation of this acid, and it is finally converted to .
Medicinal chemical studies on synthetic protease inhibitors, trans-4-guanidinomethylcyclohexanecarboxylic acid aryl esters. (1985)

trans-4-Guanidinomethylcyclohexanecarboxylic acid (trans-GMCHA) aryl esters were synthesized and tested for inhibitory effects on serine proteases, trypsin, chymotrypsin, plasmin, plasma kallikrein, pancreatic kallikrein, urokinase and thrombin. In general, these compounds showed strong inhibitory effects on chymotrypsin, pancreatic kallikrein and urokinase, but the effects varied greatly depending on the substituent in the benzene nucleus. Some of the trans-GMCHA aryl esters strongly inhibited compound 48/80-induced histamine release from mast cells / the p-tert-butylphenyl ester was especially active.
Control of apical membrane chloride permeability in the renal A6 cell line by nucleotides (1999)

1. The effect of extracellular nucleotides applied on the apical side of polarised A6 cells grown on permeant filters was investigated by measuring the changes in (i) the 36Cl efflux through the apical membranes, (ii) the intracellular chloride concentrations (aCli, measured with N-(6-methoxyquinolyl) acetoethyl ester, MQAE), (iii) ICl, the short-circuit current in the absence of Na+ transport and (iv) the characteristics of the apical chloride channels using a patch-clamp approach. 2. ATP or UTP (0.1-500 microM) transiently stimulated ICl. The sequence of purinergic agonist potencies was UTP = ATP > ADP >> the P2X-selective agonist beta,gamma-methylene ATP = the P2Y-selective agonist 2-methylthioATP. Suramin (100 microM) as the P2Y antagonist Reactive Blue 2 (10 microM) had no effect on the UTP (or ATP)-stimulated current. These findings are consistent with the presence of P2Y2-like receptors located on the apical membranes of A6 cells. Apical application of adenosine also transiently increased ICl. This effect was blocked by theophylline while the UTP-stimulated ICl was not. The existence of a second receptor, of the P1 type is proposed. 3. ATP (or UTP)-stimulated ICl was blocked by apical application of 200 microM N-phenylanthranilic acid (DPC) or 100 microM niflumic acid while 100 microM glibenclamide was ineffective. 4. Ionomycin and thapsigargin both transiently stimulated ICl; the nucleotide stimulation of ICl was not suppressed by pre-treatment with these agents. Chlorpromazin (50 microM), a Ca2+-calmodulin inhibitor strongly inhibited the stimulation of ICl induced either by apical UTP or by ionomycin application. BAPTA-AM pre-treatment of A6 cells blocked the UTP-stimulated ICl. Niflumic acid also blocked the ionomycin stimulated ICl. 5. A fourfold increase in 36Cl effluxes through the apical membranes was observed after ATP or UTP application. These increases of the apical chloride permeability could also be observed when following aCli changes. Apical application of DPC (1 mM) or 5-nitro-2(3-phenylpropylamino)benzoic acid (NPPB; 500 microM) produced an incomplete inhibition of 36Cl effluxes through the apical membranes in ATP-stimulated and in untreated monolayers. 6. In single channel patch-clamp experiments, an apical chloride channel with a unitary single channel conductance of 7.3 +/- 0.6 pS (n = 12) was usually observed. ATP application induced the activation of one or more of these channels within a few minutes. 7. These results indicate that multiple purinergic receptor subtypes are present in the apical membranes of A6 cells and that nucleotides can act as modulators of Cl- secretion in renal cells.
On the Enhanced Stability of the Guanine−Cytosine Base-Pair Radical Cation (1996)

Ab initio (UHF/6-31G*) and density functional (Becke3LYP/D95*) calculations have been used to investigate the structures and stabilities of the radical cations of the DNA bases and base pairs. The calculated structures of the base pairs show excellent agreement with crystallographic data. The most easily oxidizable base, guanine, forms a particularly stable radical cation base pair with cytosine, so that the calculated adiabatic ionization potential for the guanine−cytosine hydrogen-bonded complex is about 0.75 eV lower than that of guanine itself. UBecke3LYP/D95*//UHF/6-31G* calculations show that the shift of the central hydrogen-bonded proton at N1 of guanine to N3 of cytosine is only slightly endothermic (+1.6 kcal mol-1). The product of the corresponding proton shift in the adenine−thymine system is unfavorable by +14.1 kcal mol-1. These results suggest that the guanine−cytosine radical cation represents even more of a thermodynamic sink in oxidized DNA than might be concluded from the ionization potentials of the individual bases, and that it enjoys about 7.3 kcal mol-1 extra stabilization from the central low-barrier hydrogen bond.