gebhart/patrepeval huggingface dataset:
The Orvinols and Related Opioids - High Affinity Ligands with Diverse Efficacy Profiles (2004)

The thevinols and orvinols derived from thebaine via the thebaine-methylvinyl ketone adduct (thevinone) were thoroughly investigated in the 1960's and 1970's by the Reckitt group. From this work a number of important opioids emerged. Buprenorphine is a mu partial agonist, kappa/delta-antagonist that is now used primarily in the treatment of heroin abuse and dependence though it was initially launched as an analgesic for the treatment of moderate to severe pain. Etorphine and dihydroetorphine are very potent mu agonists that have found application in veterinary and human medicine respectively. Diprenorphine is primarily a mu antagonist though it also has some kappa-partial agonist effects. It has high affinity for all types of opioid receptors and as a "universal" opioid ligand has been much in demand as a pharmacological tool. It has also been converted into a [11C] version for use in Positron Emission Tomography (PET) studies of brain function related to the opioid receptor system. More recent medicinal chemistry investigations have been concerned with gaining a greater understanding of buprenorphine's unique opioid profile. This has involved the synthesis and evaluation of a number of series of buprenorphine analogues in which the C20 t-butyl group has been constrained in a ring system. These studies have suggested that the methyls in the t-butyl group inhibit the conformational changes in the kappa-receptor required for generation of an agonist response. Introduction of a 7alpha-cinnamoylaminomethyl group in place of the orvinol tertiary alcohol function leads to selective irreversible mu antagonism.
Innerkristalline Quellung und Schichteinschlußverbindungen von Calcium-mono-methyl- und Calcium-mono-äthylphosphorsäureester (1962)

Calcium-mono-methyl- und Calcium-mono-äthylphosphorsäureester bilden orthorhombische Schichtengitter und sind zu einer begrenzten eindimensionalen innerkristallinen Quellung mit Wasser, Ammoniak, Blausäure, Alkoholen, Phenolen, Äthern, Ketonen, Aminen und Carbonsäuren befähigt. Beim Abbau der unter Alkohol gequollenen Proben lassen sich definierte Zwischenstufen der Zusammensetzung {Ca PO 4 R · H 2 O} · 0,5 ROH gewinnen, die als Schichteinschlußverbindungen aufzufassen sind.
Phosphorylation sites in the amino-terminal region of mouse p53. (1992)

Phosphorylation is an attractive mechanism for regulating the functions of p53. The p34cdc2 kinase, which is involved in regulation of the cell cycle, phosphorylates serine-315 of human p53 in vitro. Casein kinase II phosphorylates serine-389 of mouse p53 in vitro. The amino-terminal region of mouse p53 contains a cluster of potential serine phosphorylation sites. Those sites have been proposed to be sites for phosphorylation by a double-stranded DNA-dependent kinase (DNA-PK) from HeLa cells and can be dephosphorylated by protein phosphatase 2A. To identify in vivo phosphorylation sites in the amino-terminal region of mouse p53, we mutated potential phosphorylation sites and analyzed the mutant proteins by tryptic phosphopeptide mapping. We identified serine-7, -9, -18, and -37 as in vivo phosphorylation sites. We further showed that mouse p53 expressed in bacteria is phosphorylated by DNA-PK on amino-terminal serine residues in vitro.
Immune responses induced by intranasal imiquimod and implications for therapeutics in rhinovirus infections (2005)

Notwithstanding the progress recently made in immunology and virology, there is yet no effective, specific treatment for the common cold. Symptomatic treatment is minimally effective. An anecdotal report of rapid clearing of the common cold of recent onset after intranasal application of imiquimod in several subjects by one of the authors, made us test the hypothesis that this treatment works through the secretion of interferon by the nasal mucosa. We decided to do an animal study in primates (Indian Macaca Mulata): 5 treatment and 3 control animals were used. Imiquimod or placebo was massaged into the nares of the animals and periodic samples of post-nasal fluid were taken and measurements for Interferon alpha (IFNalpha) and Tumor Necrosis Factor alpha (TNFalpha) were made by ELISA methods, and kinetic studies. mRNA IFNalpha was also isolated and analyzed by quantitative competitive RT-PCR. The internal standard was constructed to be complementary to and compete with oligonucleotide primers and for amplification of target sequences. One intranasal application of imiquimod rapidly (1-4 Hours) induced high levels of mRNA for IFNalpha, and minimal levels in the control animals. Rapid induction of INFalpha, and proportional increase of TNFalpha sustained for 4 and 6 hours respectively were noted. No adverse reactions to treatment were found in macaques during this short period of intranasal imiquimod usage (except in one macaque with a short period of lacrimation). No animal had cytotoxic effects when examined at 6 hr, 12 hr, 24 hr or 48 hr, except one animal, which had an episode of lacrimation for 6 hr post treatment. Thus both safety and efficacy of short treatment with imiquimod is proven in this animal model. Proof of principle for intranasal treatment of the common cold with imiquimod is shown. We think that this work will encourage a number of double blind clinical trials to confirm the effectiveness of the intranasal treatment of the common cold with imiquimod.
Joint Dereverberation and Residual Echo Suppression of Speech Signals in Noisy Environments (2008)

<para xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> Hands-free devices are often used in a noisy and reverberant environment. Therefore, the received microphone signal does not only contain the desired near-end speech signal but also interferences such as room reverberation that is caused by the near-end source, background noise and a far-end echo signal that results from the acoustic coupling between the loudspeaker and the microphone. These interferences degrade the fidelity and intelligibility of near-end speech. In the last two decades, postfilters have been developed that can be used in conjunction with a single microphone acoustic echo canceller to enhance the near-end speech. In previous works, spectral enhancement techniques have been used to suppress residual echo and background noise for single microphone acoustic echo cancellers. However, dereverberation of the near-end speech was not addressed in this context. Recently, practically feasible spectral enhancement techniques to suppress reverberation have emerged. In this paper, we derive a novel spectral variance estimator for the late reverberation of the near-end speech. Residual echo will be present at the output of the acoustic echo canceller when the acoustic echo path cannot be completely modeled by the adaptive filter. A spectral variance estimator for the so-called late residual echo that results from the deficient length of the adaptive filter is derived. Both estimators are based on a statistical reverberation model. The model parameters depend on the reverberation time of the room, which can be obtained using the estimated acoustic echo path. A novel postfilter is developed which suppresses late reverberation of the near-end speech, residual echo and background noise, and maintains a constant residual background noise level. Experimental results demonstrate the beneficial use of the developed system for reducing reverberation, residual echo, and background noise. </para>
Detection of transient protein–protein interactions by bimolecular fluorescence complementation: The Abl‐SH3 case (2007)

Protein-protein interactions are essential in most biological processes. Many proteomic approaches have succeeded in the identification of strong and obligatory interactions but the study of weak and transient protein-protein interactions is still a challenge. The aim of the present study was to test the ability of bimolecular fluorescence complementation to detect and discriminate in vivo weak intracellular protein interactions. As a test case, the interaction of the SH3 domain from the c-Abl tyrosine kinase with both natural and designed targets has been chosen. The reassociation of functional yellow fluorescent protein (YFP) from its fragments requires previous binding between the SH3 domain and its partners; but once this occurs, the complex is trapped, turning transient SH3 interactions into stable, easily detectable ones. The method is very sensitive and can be implemented for proteomic analysis of weak protein interactions using flow cytometry. The fluorescence emission is dependent on the strength of the interaction, in such a way that it can be used, at least qualitatively, to screen for best binding candidates among similar proline-rich peptides. In addition, it is illustrated how this method can be used to gain structural insights into particular c-Abl SH3 interactions.
Double trouble: para-neoplastic anti-PCA-2 and CRMP-5-mediated small fibre neuropathy followed by chorea associated with small cell lung cancer and evolving radiological features (2016)

Patients with Purkinje cell cytoplasmic autoantibody type 2 (PCA-2) and collapsin response-mediator protein-5 (CRMP-5) autoantibody can present with multifocal elements of encephalomyeloneuropathy. Except for an anecdotal report, case descriptions of paraneoplastic small fibre neuropathy are lacking. We report paraneoplastic small fibre neuropathy followed by chorea associated with small cell lung cancer. A man aged 57 years with a 35 pack-year smoking history presented with painless subacute paresthesia and weight fluctuation. A non-length-dependent small fibre neuropathy was confirmed by skin biopsy. Further testing revealed positive serum PCA-2 and CRMP-5 autoantibodies, which after positron emission tomography-CT led to histological confirmation of a small cell lung cancer. Initially, abnormal MRI and cerebrospinal fluid studies suggested central nervous system (CNS) involvement which was subclinical; however, 6 months later during antitumour therapy, the patient became symptomatic with choreoathetosis. After combined chemoradiation as well as immunosuppressive and symptomatic therapies, the clinical course stabilised, although residual neurological deficits remained at follow-up a year later. Coexistent PCA-2 and CRMP-5 autoantibodies may occur in the setting of small fibre peripheral neuropathy and choreoathetosis and predict cancer type. Two paraneoplastic syndromes can present successively over months; subclinical CNS involvement with evolving basal ganglia abnormalities can be a paraneoplastic manifestation. In the appropriate clinical setting, paraneoplastic testing should be considered in patients presenting with small fibre neuropathy.
Global (interconnect) warming (2001)

This article presents a comprehensive analysis of the thermal effects in advanced high-performance VLSI interconnect systems arising due to self-heating under various circuit conditions, including electrostatic discharge (ESD). Technology (Cu, low-k, etc.) and scaling effects on the thermal characteristics of the interconnects, and on their electromigration (EM) reliability, have been analyzed simultaneously, which have important implications for providing robust and aggressive deep sub-micron (DSM) interconnect design guidelines. The analysis takes into account the effects of increasing interconnect (Cu) resistivity with decreasing line dimensions and the effect of a finite barrier metal thickness. Furthermore, the impact of these thermal effects on the design (driver sizing) and optimization of the interconnect length between repeaters at the global-tier signal lines are investigated. Finally, the reliability implications for minimum-sized vias in optimally buffered signal nets will also be quantified.
Computational and Functional Evaluation of a Microfluidic Blood Flow Device (2007)

The development of microfluidic devices supporting physiological blood flow has the potential to yield biomedical technologies emulating human organ function. However, advances in this area have been constrained by the fact that artificial microchannels constructed for such devices need to achieve maximum chemical diffusion as well as hemocompatibility. To address this issue, we designed an elastomeric microfluidic flow device composed of poly (dimethylsiloxane) to emulate the geometry and flow properties of the pulmonary microcirculation. Our chip design is characterized by high aspect ratio (width > height) channels in an orthogonally interconnected configuration. Finite element simulations of blood flow through the network design chip demonstrated that the apparent pressure drop varied in a linear manner with flow rate. For simulated flow rates <250 mul min, the simulated pressure drop was <2000 Pa, the flow was laminar, and hemolysis was minimal. Hemolysis rate, assayed in terms of [total plasma hemoglobin (TPH) (sample - control)/(TPH control)] during 6 and 12 hour perfusions at 250 mul/min, was <5.0% through the entire period of device perfusion. There was no evidence of microscopic thrombus at any channel segment or junction under these perfusion conditions. We conclude that a microfluidic blood flow device possessing asymmetric and interconnected microchannels exhibits uniform flow properties and preliminary hemocompatibility. Such technology should foster the development of miniature oxygenators and similar biomedical devices requiring both a microscale reaction volume and physiological blood flow.
Novel dual multiplex real-time RT-PCR assays for the rapid detection of SARS-CoV-2, influenza A/B, and respiratory syncytial virus using the BD MAX open system (2021)

SARS-CoV-2 has spread rapidly, causing deaths worldwide. In this study, we evaluated the performance of the BD MAX Open System module for identifying viral pathogens, including SARS-CoV-2, in nasopharyngeal specimens from individuals with symptoms of upper respiratory tract infection. We developed and validated a rapid total nucleic acid extraction method based on real-time reverse transcription-polymerase chain reaction (RT-PCR) for the reliable, high-throughput simultaneous detection of common cold viral pathogens using the BD MAX Platform. The system was evaluated using 205 nasopharyngeal swab clinical samples. For assessment of the limit of detection (LoD), we used SARS-CoV-2, influenza A/B, and respiratory syncytial virus (RSV) RNA standards. The BD MAX dual multiplex real-time RT-PCR panel demonstrated a sensitivity comparable to that of the World Health Organization-recommended SARS-CoV-2 assay with an LoD of 50 copies/PCR. The LoD of influenza A/B and RSV was 100-200 copies/PCR. The overall percent agreement between the BD MAX panel and laboratory-developed RT-PCR test on 55 SARS-CoV-2-positive clinical samples was 100%. Among the 55 positive cases of COVID-19 analysed, no coinfection was detected. The BD MAX rapid multiplex PCR provides a highly sensitive, robust, and accurate assay for the rapid detection of SARS-CoV-2, influenza A/B, and RSV.
Tissue Plasminogen Activator: The Biochemistry and Pharmacology of Variants Produced by Mutagenesis (1990)

Due to the massive data sets available for drug candidates, modern drug discovery has advanced to the big data era. Central to this shift is the development of artificial intelligence approaches to implementing innovative modeling based on the dynamic, ...Read More
Interrelations between selected soil characteristics and arylsulfatase and urease activities (1980)

Abstract Six field sites in western Oregon were examined periodically over one year for arylsulfatase and urease activities as well as a variety of chemical and physical soil characteristics. Two of the sites were under forest vegetation, one was under native grasses and three were under clover/grass pasture. The interactions between the enzymatic activities and the variations in the soil characteristics were analyzed using a variety of statistical programs. Both enzymes were most highly correlated with soil organic matter content (r = 0.58 for arylsulfatase and r = 0.59 for urease). Multiple regression analysis indicated that the variability was partially accounted for by the soil parameters monitored (arylsulfatase r2 = 0.657, urease r2 = 0.509). Principal component analysis generated four factors which, when combined, accounted for 65% of the observed variation in both arylsulfatase and urease activity. Seasonal fluctuations were recorded for both of the enzymes and the levels of activity apparently fluctuated in relation to moisture and temperature conditions. The availability of certain nutrients in the soil appeared to be an important parameter associated with the level of the activity for both enzymes.
Analysis of cationic and amphoteric surfactants: V. structural analysis of the amphoteric surfactants obtained by the reaction of 1‐(2‐Hydroxyethyl)‐2‐alkyl‐2‐imidazoline with sodium monochloroacetate (1983)

Abstract Structural analysis of the amphoteric surfactants obtained by the reaction of l‐(2‐hydroxyethyl)‐2‐alkyl‐2‐imidazoline (HEAI) with sodium monochloroacetate has been carried out. These amphoteric surfactants were hydrolyzed under aqueous alkaline media, followed by acid hydrolysis to afford fatty acid and diamine derivatives. The resulting diamine derivatives were identified by the isolation and their syntheses, and were quantitatively analyzed by gas chromatography. Based upon the results of these analyses, it has been found that the reaction products can be divided into two typical types. The reaction products have simpler compositions than those of ethyl acrylate. However, these amphoteric surfactants are characterized by the presence of appreciable amounts of hydrolysis products of amides, soap and free diamine derivative XI.
Cutinase-Like Enzyme from the Yeast <i>Cryptococcus</i> sp. Strain S-2 Hydrolyzes Polylactic Acid and Other Biodegradable Plastics (2005)

A purified lipase from the yeast Cryptococcus sp. strain S-2 exhibited remote homology to proteins belonging to the cutinase family rather than to lipases. This enzyme could effectively degrade the high-molecular-weight compound polylactic acid, as well as other biodegradable plastics, including polybutylene succinate, poly (epsilon-caprolactone), and poly(3-hydroxybutyrate).
Major histocompatibility complex class I‐restricted presentation of influenza virus nucleoprotein peptide by B lymphoma cells harboring an antibody gene antigenized with the virus peptide (1995)

We analyzed the capacity of B cells to process and present a peptide from the variable region of an endogenous immunoglobulin heavy (H) chain to a major histocompatibility complex (MHC) class I-restricted cytotoxic T lymphocyte (CTL) clone. The H-chain gene was engineered to express 14-amino acid peptide from the sequence of the influenza virus nucleoprotein (NP) antigen in the third complementarity-determining region (CDR3). This NP peptide is presented in association with the Db allele in H-2b mice. We demonstrate that B lymphoma cells (H-2b) harboring the antigenized H-chain gene process and present the NP peptide in association with the Db molecule and are lysed by a CTL clone specific for that peptide in an MHC-restricted way. In contrast, the soluble antigenized antibody failed to mediate lysis of H-2b target cells. The endogenously processed immunoglobulin CDR3 peptide could be eluted from surface Db molecules in transfected cells. This study formally demonstrates that peptides from the hypervariable loops of endogenous immunoglobulin are processed through the endogenous degradative pathway and are presented to CD8+ T cells in the context of MHC class I molecules. The implication of these findings for processing and presentation of endogenous immunoglobulin peptides in B cells and network regulation by idiopeptides is discussed.
Gliovirin, a new antibiotic from <i>Gliocladium virens</i>, and its role in the biological control of <i>Pythium ultimum</i> (1983)

A compound with antibiotic activity toward Pythium ultimum was isolated from potato dextrose broth shake cultures of Gliocladium virens, a common soil mycoparasite known to inhibit but not parasitize P. ultimum. The mass spectrum and an X-ray crystallograph of the purified antibiotic indicated that it was a new diketopiperazine, and we have given it the trivial name gliovirin. Gliovirin is highly toxic to P. ultimum but is inactive against other fungi associated with cotton seedling disease. The antibiotic does not persist in nonsterile soil where it is apparently inactivated by the soil microflora.An ultraviolet light induced mutant of G. virens deficient for gliovirin production was overgrown by P. ultimum in culture and did not protect cotton seedlings from damping-off in P. ultimum infested soil. A mutant with enhanced gliovirin production was more inhibitory to P. ultimum in culture than the parent isolate and showed similar efficacy as a seedling disease suppressant, even though its growth rate was reduced when compared to the parent isolate. These results indicate that gliovirin may be important to the antagonist–pathogen interaction.
ChemInform Abstract: REACTION OF 3‐PHENYLGLYCIDIC ESTERS. PART 2. STEREO‐ AND REGIOSELECTIVITY IN THE OXIRANE RING OPENING OF METHYL TRANS‐3‐(4‐METHOXYPHENYL)GLYCIDATE WITH VARIOUS THIOPHENOLS AND THE EFFECTS OF SOLVENT AND TEMPERATURE (1985)

Abstract Der Einfluß von Lösungsmitteln und Temp. auf die Reaktion des trans‐Glycidats (I) mit verschiedenen substituierten Thiophenolen (II) in Gegenwart oder Abwesenheit eines Katalysators wird untersucht.
<i>I</i> <i>n</i> <i>s</i> <i>i</i> <i>t</i> <i>u</i> grown YBa2Cu3O7−<i>d</i> thin films from single-target magnetron sputtering (1989)

Using single-target off-axis sputter deposition, high quality superconducting films of YBa2Cu3O7−δ were made in situ. These films have properties which are distinctly different from those of bulk ceramics and of post-deposition annealed films. Their superconducting resistive transitions remain sharp regardless of the value of Tc between 75 and 86 K. Normal-state conductivities are as high or higher than the best single crystals. Critical current densities as high as 6×107 A/cm2 at 4.2 K. Tc (R=0) falls off with film thickness down to 10 K for 35–40 Å films. All of the above properties are relatively insensitive to compositional variation. The results can be explained if the in situ growth results in well-formed CuO2 planes with defects occurring elsewhere.
Immunosurgical approach to the treatment of malignant melanoma using 2,4-dinitrochlorobenzene (DNCB). (1984)

Non-specific local immunotherapy using 2,4-dinitrochlorobenzene (DNCB) was combined with additional excision of the primary melanoma. The treatment was completed by elective nodal dissection in cases of high risk invasive lesions. DNCB was also given in cases with advanced disease for the control of cutaneous lesions and disseminated metastases, respectively. Histological changes of regressed skin nodules and ways of DNCB administration are described. Comparison between surgery alone and the immunosurgical treatment was considered inappropriate at the present time due to limited number of cases.
Understanding the strobilurin fungicides (2001)

Dave W. Bartlett, John M. Clough, Chris R. A. Godfrey, Jeremy R. Godwin, Alison A. Hall, Steve P. Heaney and Steve J. Maund from Syngenta at Jealott's Hill International Research Centre discuss the biology, ecology and resistance management of the strobilurins, especially picoxystrobin, the latest member of the class.