gebhart/patrepeval huggingface dataset:
Wave-number-based assessment of the doubly asymptotic approximation. II. Frequency and time domain response (2000)

In part I, the surface variational principle (SVP) and the doubly asymptotic approximation (DAA) were used to generate alternative descriptions of the frequency domain wet surface impedance. These are used here to obtain alternative descriptions of the displacement field in slender hemicapped cylindrical shells. This field is represented as a decomposition into a two-dimensional wave-number space. The responses that are obtained are frequency domain transfer functions for a point force at the midplane, evaluated for a discrete set of frequencies. Solutions obtained from first- and second-order versions of DAA are compared to the SVP result. Then temporal responses are obtained by using an inverse fast Fourier transform to evaluate the convolution of the transfer functions with a prototypical temporal excitation. The results reveal that DAA and SVP differ most in the vicinity of fluid-loaded resonances. The largest disagreement is encountered for the axisymmetric portion of the response. It is shown that DAA often greatly underpredicts peak displacements and accelerations, but a few cases lead to overprediction.
Deficit in the sulfonylurea receptor KATP channel complex compromises the metabolic benefit of exercise training resulting in cardiac deficits (2005)

The sulfonylurea-receptor protein that forms the stress-responsive ATP-sensitive potassium (KATP) channel, is the identified binding site for sulfonylurea medications used widely in the treatment of type 2 diabetes mellitus. Clinical studies have indicated a compromised exertional capacity in diabetic patients treated with sulfonylureas yet the mechanism for this drug-induced impairment is unknown. Here the response following genetic ablation of KATP channel function (KO) was compared to wild-type controls following a 28-day endurance swimming protocol. While chronic aquatic training resulted in a lighter, leaner and fitter wild-type cohort, the KO manifested less augmentation in exercise capacity and lacked metabolic improvement in body fat composition and glycemic handling. Skeletal muscle analysis demonstrated myocellular defects compatible with repetitive injury/regeneration. Moreover, the continuous stress of swimming unmasked a survival disadvantage in the KO, associated with pathologic calcium-dependent structural damage in the heart, abnormal hypertrophic development and impaired cardiac function. Thus, intact function of the sulfonylurea-receptor KATP channel complex is mandatory for the attainment of the optimal physiologic benefits of exercise training while preventing injury. This work provides a mechanism for sulfonylurea-cardiovascular exercise intolerance and has wide-ranging implications for diabetic patients treated with KATP channel antagonists. Clinical Pharmacology & Therapeutics (2005) 77, P54–P54; doi: 10.1016/j.clpt.2004.12.097
Electrochemical probing of the activity of glucose oxidase embedded sol-gel matrixes (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTElectrochemical probing of the activity of glucose oxidase embedded sol-gel matrixesP. Audebert, C. Demaille, and C. SanchezCite this: Chem. Mater. 1993, 5, 7, 911–913Publication Date (Print):July 1, 1993Publication History Published online1 May 2002Published inissue 1 July 1993https://pubs.acs.org/doi/10.1021/cm00031a005https://doi.org/10.1021/cm00031a005research-articleACS PublicationsRequest reuse permissionsArticle Views479Altmetric-Citations123LEARN 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
Transfection of mitochondria: strategy towards a gene therapy of mitochondrial DNA diseases (1995)

Successes in classical gene therapies have been achieved by placing a corrected copy of a defective nuclear gene in cells. A similar gene replacement approach for a mutant mitochondrial genome is invariably linked to the use of a yet unavailable mitochondrial transfection vector. Here we show that DNA coupled covalently to a short mitochondrial leader peptide (chimera) can enter mitochondria via the protein import pathway, opening a new way for gene-, antisense-RNA- or antisense-DNA-delivery in molecular therapies. The import behavior of the purified chimera, composed of the amino-terminal leader peptide of the rat ornithine transcarbamylase (OTC) and a double stranded DNA molecule (17 bp or 322 bp), was tested by incubating with coupled and 'energized' rat liver mitochondria in the presence of reticulocyte lysate. The chimera was translocated with a high efficiency into the matrix of mitochondria utilizing the protein import pathway, independent from the size of its passenger DNA.
5-HT 4(a) Receptors Avert Opioid-Induced Breathing Depression Without Loss of Analgesia (2003)

Opiates are widely used analgesics in anesthesiology, but they have serious adverse effects such as depression of breathing. This is caused by direct inhibition of rhythm-generating respiratory neurons in the Pre-Boetzinger complex (PBC) of the brainstem. We report that serotonin 4(a) [5-HT4(a)] receptors are strongly expressed in respiratory PBC neurons and that their selective activation protects spontaneous respiratory activity. Treatment of rats with a 5-HT4 receptor-specific agonist overcame fentanyl-induced respiratory depression and reestablished stable respiratory rhythm without loss of fentanyl's analgesic effect. These findings imply the prospect of a fine-tuned recovery from opioid-induced respiratory depression, through adjustment of intracellular adenosine 3',5'-monophosphate levels through the convergent signaling pathways in neurons.
Radioiodination via D-amino acid peptide enhances cellular retention and tumor xenograft targeting of an internalizing anti-epidermal growth factor receptor variant III monoclonal antibody. (2000)

The mutant epidermal growth factor receptor variant III (EGFRvIII) has been found on gliomas and other tumors but not on normal tissues, including those that express the wild-type receptor. Monoclonal antibodies (mAbs) specific for EGFRvIII are rapidly internalized and degraded after binding to EGFRvIII-expressing cells. If anti-EGFRvIII mAbs are to be useful for radioimmunotherapy, then methods for trapping radionuclides in target cells after mAb processing are required. Because lysosomes are known to retain positively charged molecules, we have evaluated a new reagent for this purpose that uses a polycationinc peptide composed of D-amino acids (D-Lys-D-Arg-D-Tyr-D-Arg-D-Arg; D-KRYRR). D-KRYRR was first labeled using lodogen and then coupled to the murine anti-EGFRvIII mAb L8A4 via maleimido bond formation in 60% yield. In vitro assays with the U87deltaEGFR cell line indicated that internalized and total cell-associated activity for the 125I-labeled D-KRYRR-L8A4 conjugate were up to 4 and 5 times higher, respectively, than for L8A4 labeled with 131I using Iodogen. Paired-label comparisons in athymic mice with s.c. U87deltaEGFR xenografts demonstrated up to 5-fold higher tumor uptake for mAb labeled using D-KRYRR. Higher levels of radioiodine activity also were observed in kidney when L8A4 was labeled using D-KRYRR. Another paired-label study directly compared L8A4 labeled using radioiodinated D-KRYRR and L-KRYRR, and confirmed the role of D-amino acids in enhancing tumor uptake. These results suggest that D-KRYRR is a promising reagent for the radioiodination of internalizing mAbs, such as the anti-EGFRvIII mAb L8A4.
A high-brightness laser beam from a phase-locked multicore Yb-doped fiber laser array (2001)

We observed a high-brightness laser beam emitted from a closely packed array of seven Yb-doped single-mode fiber lasers embedded in a common cladding. The measured slope efficiency, greater than 65%, was achieved by clad-pumping from one end of the fiber. A theoretical model is established to provide a physical interpretation of the measured far field radiation patterns.
An interior-point method for nonlinear optimal power flow using voltage rectangular coordinates (1998)

The paper describes the solution of an optimal power flow (OPF) problem in rectangular form by an interior-point method (IPM) for nonlinear programming. Some OPF variants when formulated in rectangular form have quadratic objective and quadratic constraints. Such quadratic features allow for ease of matrix setup, and inexpensive incorporation of higher-order information in a predictor-corrector procedure that generally improves IPM performance. The mathematical development of the IPM in the paper is based on a general nonlinear programming problem. Issues in implementation to solve the rectangular OPF are discussed. Computational tests apply the IPM to both the rectangular and polar OPF versions. Test results show that both algorithms perform extremely well.
Automatic Rhythmic Performance in Max/MSP: the kin.rhythmicator (2011)

introduce a novel algorithm for automatically generating rhythms in real time in a certain meter. The generated rhythms are generic in the sense that they are characteristic of each time signature without belonging to a specific musical style. The algorithm is based on a stochastic model in which various aspects and qualities of the generated rhythm can be controlled intuitively and in real time. Such qualities are the density of the generated events per bar, the amount of variation in generation, the amount of syncopation, the metrical strength, and of course the meter itself. The kin.rhythmicator software application was developed to implement this algorithm. During a performance with the kin.rhythmicator the user can control all aspects of the performance through descriptive and intuitive graphic controls.
The changing world of cancer drug development: the regulatory bodies' perspective. (2014)

These include the shift to targeted therapies which hold the promise of personalized medicine, but also financial pressures, the call for adaptive licensing which places more emphasis on early access and post-authorization studies (patient registries, prospective interventional and observational studies) and real-life effectiveness studies, as well as the emergence of biosimilars in the oncology treatment armamentarium.
Use of synthetic peptides of influenza nucleoprotein to define epitopes recognized by class I-restricted cytotoxic T lymphocytes. (1987)

The conserved epitopes of influenza nucleoprotein (NP) recognized by class I MHC-restricted CTL from CBA (H-2k) and C57BL/10 (H-2b) mice have been defined in vitro with synthetic peptides 50-63 and 365-379, respectively. Two Db-restricted clones were described that recognize different epitopes on peptide 365-379. Finally, the recognition of complete NP was shown to be approximately 200-fold less efficient than peptide in the cytotoxicity assay. These phenomena are closely related to results with class II-restricted T cells and they strengthen the hypothesis that influenza proteins are degraded in the infected cell before recognition by class I-restricted CTL.
Predicting renal outcome in IgA nephropathy. (1997)

Immunoglobulin A (IgA) nephropathy, the most common form of glomerulonephritis worldwide, is characterized by a heterogeneous clinical course. In this study, multivariate analysis was performed to identify histopathologic and clinical features that most accurately predict adverse outcome from a dataset of 148 individuals with IgA nephropathy who underwent renal biopsy at our institution between 1973 and 1995. A semiquantitative scoring system was developed for assessment of six glomerular, eight interstitial, and six vascular histopathologic features of IgA nephropathy. Glomerular and interstitial proliferative activity was evaluated by immunostaining archival biopsy specimens with Mib-1, an antibody directed against the Ki-67 antigen. Kaplan-Meier survival analysis was performed, with renal failure being defined as onset of dialysis or transplantation. A number of clinicopathologic factors were univariately associated with adverse outcome, including elevated serum creatinine levels; the presence of hypertension; proteinuria; component and total histopathologic scores; and positive glomerular or interstitial Mib-1 scores. The total glomerular score, consisting of the arithmetic sum of each of the six component scores, was the strongest histopathologic predictor of adverse outcome. Total interstitial and vascular scores also provided more prognostic information than did individual component scores. By multivariate analysis, high total glomerular scores, increased serum creatinine levels at diagnosis, and younger age were significant (P < 0.01) independent predictors of renal failure. Our studies provide a rational basis for the inclusion of composite histopathologic scores in clinical intervention studies of patients with IgA nephropathy and other glomerular disorders.
Quantitative studies on some antagonists of N‐methyl D‐aspartate in slices of rat cerebral cortex (1985)

Coronal sections of rat brain (500 micron thick) were trimmed to form 'wedges' of tissue consisting of cerebral cortex and corpus callosum. When these slices were placed in a two-compartment bath, the cortical tissue could be depolarized, relative to the corpus callosum, by superfusions of high K+, or by amino acids such as L-glutamate, L-aspartate, quisqualate, kainate and N-methyl D-aspartate (NMDA). Responses to NMDA were reduced by magnesium ions, by the organic antagonists (-)-2-amino 5-phosphonovalerate (APV) and 2-amino 7-phosphonoheptanoate (APH), and by the dissociative anaesthetic ketamine. In this preparation, all these antagonists shifted the NMDA dose-response curve to the right in a parallel manner. A Schild plot for Mg2+ had a slope significantly less than unity, indicative of a non-competitive action, whilst Schild plots for (-)-APV, APH and ketamine appeared linear and had slopes of approximately 1. Analysis of the results of combination experiments suggested that the presumed competitive antagonists, (-)-APV and APH, share a common site of action as NMDA antagonists, and that this site is distinct from that at which ketamine exerts its action. The action of Mg2+ is clearly different from that of either (-)-APV or ketamine. It is concluded that ketamine is a non-competitive antagonist of NMDA and may act at an allosteric site on the NMDA receptor complex to influence its function.
A ribosomal calmodulin-binding protein from Dictyostelium. (1991)

Using 125I-calmodulin as a probe, we have recently identified specific Ca2+/calmodulin-binding proteins in cell extracts from the cellular slime mold, Dictyostelium discoideum: a major 22-kDa activity, a soluble 78/80-kDa protein, and several membrane-associated high Mr proteins (Winckler, T., Dammann, H., and Mutzel, R. (1991) Res. Microbiol. 142, 509-519). cDNA clones for at least two of these proteins have been isolated by ligand screening of a lambda gt11 prophage expression library. Antibodies directed against the lacZ-cDNA-encoded fusion protein from one of the clones recognized a single 22-kDa component in D. discoideum extracts which comigrated with the endogenous 22-kDa calmodulin-binding protein. The cDNA-derived nucleotide sequence predicts a protein of Mr 21,659 with 56% sequence identity (69% homology) with rat ribosomal protein L19. The endogenous 22-kDa calmodulin-binding activity was associated with ribosomes. It was found to be an integral constituent of the large ribosomal subunit, since it cosedimented with 60 S ribosomal subunits in sucrose density gradients in the presence of 0.5 M NH4Cl. Our observations point to a physiological role for calmodulin in the Ca2+ regulation of eukaryotic protein synthesis. Support for this comes from recent studies showing inhibition of protein synthesis by calmodulin antagonists in Ehrlich ascites tumor cells (Kumar, R. V., Panniers, R., Wolfman, A., and Henshaw, E.C. (1991) Eur. J. Biochem. 195, 313-319).
Opposing Regulation of Choline Deficiency-induced Apoptosis by p53 and Nuclear Factor κB (2001)

We have previously shown that fetal rat brain cells, preneuronal (PC12), and hepatocyte (CWSV-1) cells undergo apoptosis during choline deficiency (CD). The PC12 and epithelial cell culture models were used to determine the molecular mechanism by which CD induces apoptosis. Our data indicate that CD leads to both growth arrest and apoptosis in a subpopulation of cells, which correlate with the up-regulation of the tumor suppressor protein p53 and concurrent up-regulation of the cyclin-dependent kinase-inhibitor p21<sup>WAF1/CIP1</sup>. Additionally, CD induced both a G<sub>1</sub>/S and a G<sub>2</sub>/M arrest. Transient transfection of a dominant negative p53 (p53DN) construct into PC12 cells, which inhibited endogenous p53 activation, significantly reduced the induction of apoptosis associated with CD. Interestingly, CD also induced the persistent activation of the transcription factor NF-κB. Activation of NF-κB has been shown to promote cell survival and proposed to antagonize p53. Consistent with this, expression of a super-repressor form of IκBα (SR-IκBα) that functions to strongly inhibit NF-κB activation, profoundly enhanced cell death during CD. In summary, these results suggest that the effects of CD on apoptosis and subsequent cell survival are mediated through two different signaling pathways, p53 and NF-κB, respectively. Taken together, our data demonstrates the induction of opposing mechanisms associated with nutrient deficiency that may provide a molecular mechanism by which CD promotes carcinogenesis.
Microemulsions and solubilization by nonionic surfactants (2007)

The liquid isotropic solution regions in the phase diagrams of water, hydrocarbons and tetraethylene glycol dodecyl ether were determined by direct titration.The results showed that at temperatures close to the Phase Inversion Temperature, PIT, separate regions appeared which contained large amounts of solubilized oil and water. The solutions are of importance for phenomena such as microemulsions, surfactant phases and second solubilization regions.
Vaccinia virus induces apoptosis of infected macrophages (2002)

Vaccinia virus (VV) infects a broad range of host cells, and while it usually causes their lysis (i.e. necrosis), the nature of the cell-death phenomenon is not well understood. In this study, we show that VV induces apoptosis of cells of the murine macrophage line J774.G8, as revealed by morphological signs, DNA ladder formation, changes of mitochondrial membrane potential and annexin-V positivity. Apoptosis occurred in both untreated and IFN-gamma-pretreated macrophages, and could not be inhibited by aminoguanidine, a relatively specific inhibitor of inducible nitric oxide synthase. Inhibition of VV DNA synthesis and late gene expression by cytosine arabinoside also did not prevent apoptosis, while heat- or psoralen/UV-inactivated VV did not cause any apoptosis. Thus, VV early gene expression seems to be required for induction of apoptosis. At the cellular level, infection with VV induced a decrease in the levels of Bcl-x(L), an anti-apoptotic member of the Bcl-2 family. The importance of loss of Bcl-x(L) was demonstrated by prevention of VV-mediated apoptosis on expression of Bcl-2, a functional homologue of Bcl-x(L). Our findings provide evidence that induction of apoptosis by VV in macrophages requires virus early gene expression, does not involve nitric oxide, induces a decrease in mitochondrial membrane potential and is associated with altered levels of Bcl-x(L).
Polymorphisms involved in the folate metabolizing pathway and risk of multiple myeloma (2007)

Folate and methionine metabolism plays an essential role in both DNA synthesis and methylation. Polymorphisms in the genes of the folate-dependent enzymes have been shown to affect disease susceptibility. We conducted a Korean population-based case-control study to evaluate whether genetic variation in folate metabolism may have a role in the risk of multiple myeloma (MM). The study subjects were 173 patients with MM and 1,700 population-based controls. The polymorphisms studied include methylenetetrahydrofolate reductase (MTHFR) 677 C > T and 1298 A > C, methionine synthase (MS) 2756 A > G, methionine synthase reductase (MTRR) 66A > G, thymidylate synthase (TS) 28-bp repeat (2R-->3R) and 6-bp deletion/insertion. MS 2756 AG genotypes were associated with a 1.5-fold lower risk of MM (OR = 0.66, 95%CI; 0.43-0.99, P = 0.047). There was no association between MTHFR C677T, A1298C, MTRR A66G, TS 2R-->3R and 6-bp deletion/insertion polymorphisms and MM. These results suggest that MTHFR C677T, A1298C, MTRR A66G, TS 2R-->3R, and 6-bp deletion/insertion do not significantly factor into the pathogenesis of MM in the Korean population, but that MS A2756G polymorphism may play an important role.
Thieno[2,3-d]pyrimidin-4(3H)-one derivatives and 1,2-dihydrogenated homologues: synthesis, enhanced in vitro antiaggregant activity for reduced compounds. (1992)

Some derivatives of thieno[2,3-d]pyrimidin-4(3 H)-one A and their 1,2-dihydrogenated homologues B were synthesized. The study of their in vitro antiaggregating activity showed that the first compounds exhibited significant inhibiting power when aggregation was induced with ADP. Their reduction to derivatives of 1,2-dihydrothieno[2,3-d]pyrimidin-4(3 H)-one led to a new series of molecules possessing a large antiaggregant activity. When compared to that of acetylsalicylic acid under the same conditions, this activity was the same with collagen or arachidonic acid-induced aggregation, but greater when aggregation was induced by ADP. Serotonin release was also inhibited.
Chemical Reaction Equilibrium Analysis: Theory and Algorithms (1982)

The Closed-System Constraint and Chemical Stoichiometry. Chemical Thermodynamics and Equilibrium Conditions. Computation of Chemical Equilibrium for Relatively Simple Systems. Survey of Numerical Methods. Chemical Equilibrium Algorithms for Ideal Systems. Chemical Equilibrium Algorithms for Non-Ideal Systems. The Effects of Problem Parameter Changes on Chemical Equilibria (Sensitivity Analysis). Practical Considerations and Special Topics. Appendixes. List of Symbols. References. Answers to Problems. Author and Subject Indexes.
Tryptophan hydroxylase-1 regulates immune tolerance and inflammation (2012)

Nutrient deprivation based on the loss of essential amino acids by catabolic enzymes in the microenvironment is a critical means to control inflammatory responses and immune tolerance. Here we report the novel finding that Tph-1 (tryptophan hydroxylase-1), a synthase which catalyses the conversion of tryptophan to serotonin and exhausts tryptophan, is a potent regulator of immunity. In models of skin allograft tolerance, tumor growth, and experimental autoimmune encephalomyelitis, Tph-1 deficiency breaks allograft tolerance, induces tumor remission, and intensifies neuroinflammation, respectively. All of these effects of Tph-1 deficiency are independent of its downstream product serotonin. Because mast cells (MCs) appear to be the major source of Tph-1 and restoration of Tph-1 in the MC compartment in vivo compensates for the defect, these experiments introduce a fundamentally new mechanism of MC-mediated immune suppression that broadly impacts multiple arms of immunity.