gebhart/patrepeval huggingface dataset:
PhaC and PhaR Are Required for Polyhydroxyalkanoic Acid Synthase Activity in <i>Bacillus megaterium</i> (2001)

Polyhydroxyalkanoic acids (PHAs) are a class of polyesters stored in inclusion bodies and found in many bacteria and in some archaea. The terminal step in the synthesis of PHA is catalyzed by PHA synthase. Genes encoding this enzyme have been cloned, and the primary sequence of the protein, PhaC, is deduced from the nucleotide sequences of more than 30 organisms. PHA synthases are grouped into three classes based on substrate range, molecular mass, and whether or not there is a requirement for phaE in addition to the phaC gene product. Here we report the results of an analysis of a PHA synthase that does not fit any of the described classes. This novel PHA synthase from Bacillus megaterium required PhaC (PhaC(Bm)) and PhaR (PhaR(Bm)) for activity in vivo and in vitro. PhaC(Bm) showed greatest similarity to the PhaCs of class III in both size and sequence. Unlike those in class III, the 40-kDa PhaE was not required, and furthermore, the 22-kDa PhaR(Bm) had no obvious homology to PhaE. Previously we showed that PhaC(Bm), and here we show that PhaR(Bm), is localized to inclusion bodies in living cells. We show that two forms of PHA synthase exist, an active form in PHA-accumulating cells and an inactive form in nonaccumulating cells. PhaC was constitutively produced in both cell types but was more susceptible to protease degradation in the latter type. Our data show that the role of PhaR is posttranscriptional and that it functions directly or indirectly with PhaC(Bm) to produce an active PHA synthase.
Identification and reduction of ion suppression effects on pharmacokinetic parameters by polyethylene glycol 400 (2006)

Ion suppression in mass spectrometry has been described recently in detail and should always be considered during analysis by liquid chromatography/tandem mass spectrometry (LC/MS/MS) in a drug metabolism and pharmacokinetics (DMPK) environment. At best, ion suppression leads to decreased sensitivity but at worst could lead to incorrectly determined pharmacokinetic (PK) parameters. Our investigations centred on polyethylene glycol (PEG 400), an excipient often used in pre-clinical dosing vehicles. PEG was also found to be present in large quantities in the blood collection tubes used for pre-clinical PK studies. Ion suppression was observed for many analytes, either due to the use of PEG in the dosing vehicle or in blood collection tubes. The elimination of large ion suppression effects was attained by simple chromatographic gradient changes and the use of alternative blood collection tubes. The effect of the above was to increase the detected plasma concentration levels, which resulted in a change in key PK parameters.
The design of arbitrary-length cosine-modulated filter banks and wavelets, satisfying perfect reconstruction (2003)

FIR filter banks which satisfy the perfect-reconstruction (PR) property can be obtained by cosine modulation of a linear-phase prototype filter of length N=2mM, where M is the number of channels. A PR cosine-modulated filter bank is presented for which the length of the prototype filter is arbitrary. Additional regularity conditions are imposed on the filter bank to obtain the cosine-modulated orthonormal bases of compactly supported wavelets. Design examples are given.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
On the specificity of DNA-protein interactions. (1986)

In this paper we summarize the various factors that must be considered in establishing the operational specificity of the binding of a protein regulator of gene expression to a DNA target site. We consider informational (combinatorial) aspects of binding-site specification, actual recognition mechanisms, and the thermodynamics of target-site selection against a background of competing pseudospecific and non-(sequence)-specific DNA binding sites. The results provide insight into the design, specification, and possibly the evolution of regulatory proteins and their chromosomal binding targets, as well as into practical aspects of the design of regulatory-protein isolation schemes and physicochemical regulatory considerations in vivo.
A2A Adenosine Receptor Antagonists as Therapeutic Candidates: Are They Still an Interesting Challenge? (2018)

In the past decades, many efforts were undertaken to develop ligands for the adenosine receptors, with the purpose to individuate agonists and antagonists affinity and selectivity for each subtypes, namely A1, A2A, A2B, and A3. These intense studies allowed a deeper knowledge of the nature and, moreover, of the pathophysiological roles of all the adenosine receptor subtypes. In particular, the involvement of the A2A adenosine receptor subtype in some physiological mechanisms in the brain, that could be related to important diseases such as the Parkinson's disease, encouraged the research in this field. Particular attention was given to the antagonists endowed with high affinity and selectivity since they could have a real employment in the treatment of Parkinson's disease, and some compounds, such as istradefylline, preladenant and tozadenant, are already studied in clinical trials. Actually, the role of A2A antagonists in Parkinson's disease is becoming contradictory due to contrasting results in the last studies, but, at the same time, new possible employments are emerging for this class of antagonists in cancer pathologies as much interesting to legitimate further efforts in the research of A2A ligands.
Role of Human Sphingosine-1-phosphate Phosphatase 1 in the Regulation of Intra- and Extracellular Sphingosine-1-phosphate Levels and Cell Viability (2003)

Sphingosine-1-phosphate (S1P) is a highly bioactive lipid that exerts numerous biological effects both intracellularly as a second messenger and extracellularly by binding to its G-protein-coupled receptors of the endothelial differentiation gene family (S1P receptors-(1-5)). Intracellularly, at least two enzymes, sphingosine kinase and S1P phosphatase, regulate the activity of S1P by governing the phosphorylation status of S1P. To study the regulation of S1P levels, we cloned the human isoform of S1P phosphatase 1 (hSPPase1). The hSPPase1 has 78% homology to the mouse SPPase at the amino acid level with 6-8 possible transmembrane domains. Confocal microscopy revealed green fluorescent protein-tagged hSPPase1, expressed in either MCF7 or HEK293 cells, co-localized to endoplasmic reticulum with calreticulin. According to Northern blot analysis, hSPPase1 is expressed in most tissues, with the strongest levels found in the highly vascular tissues of placenta and kidney. Transient overexpression of hSPPase1 exhibited a 2-fold increase in phosphatase activity against S1P and dihydro-S1P, indicating that the expressed protein was functional. Small interfering RNA (siRNA) knockdown of endogenous hSPPase1 drastically reduced hSPPase1 mRNA levels, as confirmed by reverse transcription PCR, and resulted in an overall 25% reduction of in vitro phosphatase activity in the membrane fractions. Sphingolipid mass measurements in hSPPase1 siRNA knockdown cells revealed a 2-fold increase of S1P levels and concomitant decrease in sphingosine. In vivo labeling of hSPPase1 siRNA-treated cells showed accumulation of S1P within cells, as well as significantly increased secretion of S1P into the media, indicating that hSPPase1 regulates secreted S1P. In addition, siRNA-induced knockdown of hSPPase1 endowed resistance to tumor necrosis factor-alpha and the chemotherapeutic agent daunorubicin. Collectively, these data suggest that regulation of hSPPase1 with the resultant changes in cellular and secreted S1P could have important implications to cell proliferation, angiogenesis, and apoptosis.
Introduction to identity management risk metrics (2006)

Good metrics aggregate both objective and quantitative measures, and should be consistent, cheap to gather, and expressed as numbers. Objective measurement helps you report on past progress, forecast future scenarios, and respond to real-time events. In this paper, the author presents some identity management risk metrics that highlight the distribution, quality, affiliation, and governance of identity in a system as well as inform the decision-making process
Engineering Bioluminescent Proteins: Expanding their Analytical Potential (2009)

Bioluminescent proteins are used in a plethora of analytical methods, from ultrasensitive assay development to the in vivo imaging of cellular processes. This article reviews the most pertinent current bioluminescent-protein-based technologies and suggests the future direction of this vein of research. (To listen to a podcast about this feature, please go to the Analytical Chemistry multimedia page at pubs.acs.org/page/ancham/audio/index.html .).
Neuromuscular electrical and thermal-tactile stimulation for dysphagia caused by stroke: a randomized controlled trial (2009)

The results suggest that neuromuscular electrical stimulation combined with thermal-tactile stimulation is a better treatment for patients with swallowing disorders after stroke than thermal-tactile stimulation alone.
Stratifin (14-3-3 σ) Limits Plakophilin-3 Exchange with the Desmosomal Plaque (2013)

Desmosomes are prominent cell-cell adhesive junctions in stratified squamous epithelia and disruption of desmosomal adhesion has been shown to have dramatic effects on the function and integrity of these tissues. During normal physiologic processes, such as tissue development and wound healing, intercellular adhesion must be modified locally to allow coordinated cell movements. The mechanisms that control junction integrity and adhesive strength under these conditions are poorly understood. We utilized a proteomics approach to identify plakophilin-3 associated proteins and identified the 14-3-3 family member stratifin. Stratifin interacts specifically with plakophilin-3 and not with other plakophilin isoforms and mutation analysis demonstrated the binding site includes serine 285 in the amino terminal head domain of plakophilin-3. Stratifin interacts with a cytoplasmic pool of plakophilin-3 and is not associated with the desmosome in cultured cells. FRAP analysis revealed that decreased stratifin expression leads to an increase in the exchange rate of cytoplasmic plakophilin-3/GFP with the pool of plakophilin-3/GFP in the desmosome resulting in decreased desmosomal adhesion and increased cell migration. We propose a model by which stratifin plays a role in regulating plakophilin-3 incorporation into the desmosomal plaque by forming a plakophilin-3 stratifin complex in the cytosol and thereby affecting desmosome dynamics in squamous epithelial cells.
Tuberculin sensitivity: conversions and reversions in a rural African population. (1999)

Estimation of a convincing 'true' annual risk of infection from tuberculin survey data is not possible from either cross-sectional or longitudinal data, due to misclassifications and the instability of delayed type hypersensitivity over time. An apparent increase in infection risk with age can arise as an artefact of test instability. BCG-induced tuberculin sensitivity declines rapidly in this population in most individuals. It is necessary to consider tuberculin reversions, whether real or apparent, when interpreting tuberculin data on individuals or populations.
Nonpeptide Luteinizing Hormone-Releasing Hormone Antagonists Derived from Erythromycin A:  Design, Synthesis, and Biological Activity of Cladinose Replacement Analogues (2004)

The design and synthesis of a series of 11,12-cyclic carbamate derivatives of 6-O-methylerythromycin A that are novel, nonpeptide LHRH antagonists, is described. The macrolide antagonist 1, discovered during a screen of our chemical repository, was compared to a macrocyclic peptide antagonist 2 using molecular modeling, thus providing a model for the design of more potent antagonists. Medicinal chemistry efforts to find a replacement for cladinose at position 3 of the erythronolide core provided a series of oxazolidinone carbamates that were equally as active as the cladinose-containing parent macrolides. The descladinose LHRH antagonist 14 has 1-2 nM affinity for both rat and human LHRH receptors and is a potent inhibitor of LH release (pA2 = 8.76) in vitro. In vivo, 14 was found to produce a dose-dependent suppression of LH in male castrate rats via both i.v. and p.o. dosing.
Facet-Coating Effects on the 1.3-µm Strained Multiple-Quantum-Well AlGaInAs/InP Laser Diodes (1998)

In this paper, we report the fabrication and characteristics of 1.3-µm strained multiple-quantum-well ridge-waveguide AlGaInAs/InP laser diodes and the influence of reflective films on threshold current, slope efficiency, characteristic temperature and long-term reliability. A higher characteristic temperature and improved linearity of CW light-current characteristics can be obtained by increasing the facet reflectivity. With a high reflectivity coating of 70% on the front facet and 90% on the rear facet, the laser diodes exhibit a high characteristic temperature of 92 K, an output power of 15 mW at 120°C, and only 0.7 dB slope efficiency drop at the output power of 30 mW and 20°C. Long-term aging was applied to test the facet-coating reliability using the constant power mode of 10 mW at 85°C. The laser diodes have exhibited stable operation up to 6000 h and no significant degradation has been observed.
Abrogation of in vitro suppression of human immunodeficiency virus type 1 (HIV-1) replication mediated by CD8+ T lymphocytes of asymptomatic HIV-1 carriers by staphylococcal enterotoxin B and phorbol esters through induction of tumor necrosis factor alpha (1997)

CD8+ T lymphocytes of asymptomatic human immunodeficiency virus type 1 (HIV-1) carriers (AC) suppress HIV-1 replication in vitro. Failure of host defense mechanisms and increased virus proliferation are associated with disease progression. The exact mechanisms inducing these changes at the advanced stage of the disease are still obscure. In this study, we searched for experimental conditions favoring the abrogation of the suppression of viral replication in peripheral blood mononuclear cells (PBMC) of AC by using various pharmacological and biological probes modifying cell activation. Among such agents, staphylococcal enterotoxin B (SEB) and phorbol 12-myristate 13-acetate (PMA) markedly increased otherwise low levels of HIV-1 replication in cultures of phytohemagglutinin-stimulated AC PBMC following in vitro HIV-1 LAI infection. A similar but less pronounced virus induction was also observed in macrophage-tropic HIV-1. Individual pretreatment of CD4+ and CD8+ PBMC fractions with these agents caused a reduction in CD8+ cell proliferation and enhanced HIV-1 replication in CD4+ cells. SEB- and PMA-mediated augmentation of HIV-1 replication in AC PBMC was significantly blocked by neutralizing antibody to tumor necrosis factor-alpha (TNF-alpha), although recombinant TNF-alpha alone failed to reproduce the effects of SEB or PMA. Our results suggest that the induction of TNF-alpha may be one of the mechanisms that overcomes the CD8+-induced suppression of HIV-1 replication in AC and that it may induce HIV-1 replication.
Partial treatment of wind turbine blades with radar absorbing materials (RAM) for RCS reduction (2010)

The application of radar absorbing materials (RAM) in order to reduce the interference of wind farms with radar systems is considered as a possible mitigation solution. This paper will address the key challenges when trying to efficiently apply RAM to certain parts of the wind turbine blades to significantly reduce the scattering of radar signals. Modeling of the radar cross-section (RCS) is presented for a generic 40 meter blade wind turbine before and after applying RAM to different parts of the blade. The results of modeling possible solutions of partially RAM treated blades are compared.
DNA sequences Homologous to the <i>Drosophila</i> opa Repeat are Present in Murine mRNAs That are Differentially Expressed in Fetuses and Adult Tissues (1987)

A mouse embryonic cDNA containing two opa-like (CAX)n repeats was isolated on the basis of its cross-hybridization with a Drosophila K10 cDNA. Such repeated sequences were present in different murine mRNAs, some of which were specifically expressed during fetal life or in different adult tissues. This suggests that, as already described for Drosophila, opa-like sequences are parts of proteins involved in ontogenic or cell-type-specific functions in vertebrates. However, unlike Drosophila, such repeated sequences were not found within the murine homeo-boxes containing genes of the Hox-1 complex.
Synthesis, Characterization, and Selected Properties of 7‐ and 12‐Ammoniocarba‐<i>closo</i>‐dodecaboranes (2012)

Abstract The inner salts 12‐H 3 N‐ closo ‐1‐CB 11 H 11 (H 1 ) and 7‐H 3 N‐12‐Hal‐ closo ‐1‐CB 11 H 10 [Hal = F (H 3 ), Cl (H 4 )] were synthesized by a microwave‐assisted Buchwald–Hartwig amination starting from the corresponding monoiodinated { closo ‐1‐CB 11 } clusters and LiN(SiMe 3 ) 2 . H 1 was methylated to result in the zwitterion 12‐Me 3 N‐ closo ‐1‐CB 11 H 11 ( 2 ). All new compounds were characterized by multinuclear NMR spectroscopy, elemental analysis, and mass spectrometry. The crystal structures of H 1· Me 2 CO and 2 were determined. The p K a value of H 1 in aqueous solution was estimated by potentiometric titration and by 11 B{ 1 H} NMR spectroscopic studies. The stepwise deprotonation of H 1 with n BuLi in [D 8 ]THF was studied by multinuclear NMR spectroscopy. In a first step, the amine 1 is obtained and then the amide [12‐HN‐ closo ‐1‐CB 11 H 11 ] 2– and finally the trianion [12‐HN‐ closo ‐1‐CB 11 H 10 ] 3– or more probably lithiated species thereof are formed. The experimental spectroscopic and structural data, as well as the p K a value of H 1 are compared to values derived from DFT and ab initio calculations.
The Implications of Constraint in Lumbar Total Disc Replacement (2003)

Lumbar total disc replacement (TDR) is an evolving technique that has the potential to replace arthrodesis as the gold standard surgical treatment of degenerative disc disease. The interaction between host anatomy and physiology and the biomechanical properties of TDR implants will determine the quality of long-term clinical results. However, there is scant literature addressing this subject. The purpose of this article is to discuss the implications of biomechanical constraint in TDR. Based upon available data for normal motion segments and the design of two TDRs currently in clinical trials, unconstrained designs appear to have a kinematic advantage. They are more likely to provide a physiologic mobile instantaneous axis of rotation (IAR), which may explain why they display greater range of motion in vivo. Their lack of constraint may prevent excessive facet joint or capsuloligamentous loads in the extremes of flexion and extension. Furthermore, since the IAR is mobile, they may be less sensitive to small errors in implant placement. On the other hand, constrained devices appear to have an advantage in protection of the posterior elements from shear loading. Spinal shear loads of considerable magnitude occur during activities of daily living. Whether the transference of stresses to the implant and implant-bone interface is clinically significant is unknown. Although this article focuses on two specific TDR designs, future designs will need to account for the same kinematic and loading concerns regarding constraint. We hope this discussion will assist clinicians and researchers in the design, selection, and clinical comparison of present and future TDR implants.
Laser induced fluorometric analysis of drugs (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTLaser induced fluorometric analysis of drugsNorman. Strojny and J. Arthur F. De SilvaCite this: Anal. Chem. 1980, 52, 11, 1554–1559Publication Date (Print):September 1, 1980Publication History Published online1 May 2002Published inissue 1 September 1980https://pubs.acs.org/doi/10.1021/ac50061a004https://doi.org/10.1021/ac50061a004research-articleACS PublicationsRequest reuse permissionsArticle Views120Altmetric-Citations17LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
[Effect of intravenous injection of aspirin on the cochlea]. (1992)

It is not yet well understood how aspirin acts on the auditory system. This study was aimed at elucidating the effects of aspirin on the cochlear hair cells and cochlear nerve of guinea pigs by recording (1) spontaneous activity of cochlear nerve fibers, (2) compound action potentials (CAPs) evoked by electrical pulses applied to the cochlea through the round window membrane, (3) acoustically evoked action potentials (APs) through the round window membrane and (4) acoustic emissions (sound pressure near the tympanic membrane) evoked by electrical pulses applied to the cochlea. The following results were obtained. (1) After guinea pigs were given aspirin (200 mg/kg) intravenously, a transient reduction in spontaneous activity of cochlear nerve fibers and elevation over the subsequent 10-20 minutes were observed in three of four fibers recorded for more than 30 minutes. The mean spontaneous discharge rate in 102 fibers after aspirin administration (200 mg/kg) was not significantly higher than the control values from 30 to 120 minutes after aspirin administration, while the rate in 112 fibers after aspirin administration (400 mg/kg) was significantly higher. (2) After injecting of 100 mg/kg, 200 mg/kg and 400 mg/kg of aspirin, the amplitude of electrically evoked CAPs decreased significantly, while their latency increased significantly only after injection of 400 mg/kg of aspirin. (3) Changes in the amplitude of acoustically evoked APs and electrically evoked CAPs were compared before and after intravenous injections of 400 mg/kg of aspirin. The AP suppression ratio at low sound intensity was significantly greater than that of CAPs at low and high current levels. (4) After injection of 400 mg/kg of aspirin, the waves of electrically evoked acoustic emissions and their peaks in the frequency analysis disappeared either reversibly or irreversibly. The observed changes in spontaneous activity of cochlear nerve fibers in response to aspirin administration to guinea pigs may represent a tinnitus-like phenomenon. The detection of electrically evoked CAPs suggests that aspirin acts on the cochlear nerve and causes a decrease in its excitability, and the discovery of acoustically evoked APs and electrically evoked acoustic emissions is interpreted as indicating that aspirin acts not only on the cochlear nerve but also on cochlear hair cells.