gebhart/patrepeval huggingface dataset:
A heuristic wavelength assignment algorithm for multihop WDM networks with wavelength routing and wavelength reuse (2002)

The authors present a heuristic algorithm for effectively assigning a limited number of wavelengths among the access stations of a multihop network wherein the physical medium consists of optical fiber segments which interconnect wavelength-selective optical switches. Such a physical medium permits the limited number of wavelengths to be re-used among the various fiber links, thereby offering very high aggregate capacity. Although the optical connectivity among the access station can be altered by changing the states of the various optical switches, the resulting optical connectivity pattern is constrained by the limitation imposed at the physical level. They also present and study two admission control schemes, used to admit or reject requests for virtual connections. The heuristic is tested on a realistic traffic model, and the call blocking performance of new requests for virtual connections is studied through extensive simulations and compared against the blocking performance of an ideal infinite capacity centralized switch (lowest possible call blocking caused exclusively by congestion on the finite capacity user input/output links, never by the switch fabric itself). Surprisingly, they find that, for a wide range of parameters, the blocking performance of the lightwave network is almost the same as that of the ideal centralized switch. From these results, they conclude that the heuristic algorithm is effective and the admission control scheme is efficient.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with bortezomib in multiple myeloma (2012)

Histone deacetylase (HDAC) enzymatic activity has been linked to the transcription of DNA in cancers including multiple myeloma (MM). Therefore, HDAC inhibitors used alone and in combination are being actively studied as novel therapies in MM. In the present study, we investigated the preclinical activity of ACY-1215, an HDAC6-selective inhibitor, alone and in combination with bortezomib in MM. Low doses of ACY-1215 combined with bortezomib triggered synergistic anti-MM activity, resulting in protracted endoplasmic reticulum stress and apoptosis via activation of caspase-3, caspase-8, and caspase-9 and poly (ADP) ribosome polymerase. In vivo, the anti-MM activity of ACY-1215 in combination with bortezomib was confirmed using 2 different xenograft SCID mouse models: human MM injected subcutaneously (the plasmacytoma model) and luciferase-expressing human MM injected intravenously (the disseminated MM model). Tumor growth was significantly delayed and overall survival was significantly prolonged in animals treated with the combination therapy. Pharmacokinetic data showed peak plasma levels of ACY-1215 at 4 hours after treatment coincident with an increase in acetylated α-tubulin, a marker of HDAC6 inhibition, by immunohistochemistry and Western blot analysis. These studies provide preclinical rationale for acetylated α-tubulin use as a pharmacodynamic biomarker in future clinical trials.
Arytenoid motion evoked by regional electrical stimulation of the canine posterior cricoarytenoid muscle (1994)

Anatomical studies have demonstrated that the posterior cricoarytenoid muscle in the dog is composed of three bellies. These bellies are termed vertical, oblique, and horizontal on the basis of their orientation. The purpose of this study was to show whether each of these bellies can move the vocal fold in different ways. Ten anesthetized dogs underwent laryngectomies while paralyzed with curare. The posterior cricoarytenoid muscles were then exposed by dissecting the overlying esophageal mucosa. Electrical stimulation was applied to each belly, and the motion of the arytenoid cartilage was measured. Because the oblique belly overlies the vertical belly, they were usually stimulated together. It was found that the vertical and oblique bellies rock the arytenoid backwards while sliding it laterally, thus causing a maximal dilation of the airway. The horizontal belly caused a swiveling motion of the arytenoid. It is proposed that the vertical and oblique bellies normally cause vocal fold abduction during respiration, while the horizontal belly primarily is used to adjust finely the position of the vocal process during phonation. Because the human posterior cricoarytenoid is also composed of separate bellies it, too, may have distinct functions.
MR, CT, and Ultrasonographic Demonstration of Splenic Vein Thrombosis (1984)

The first case report of magnetic resonance imaging of splenic vein thrombosis is presented together with CT and ultrasound correlation.
Fluorescent excitation transfer immunoassay. A general method for determination of antigens. (1976)

A general immunochemical method for the assay of haptens and proteins has been devised and applied to morphine, a morphine-albumin conjugate, and human immunoglobulin G. A fluorescein-labeled antigen and a quencher-labeled antibody are employed. By use of fluorescein and rhodamine as the fluorescer and quencher, respectively, dipole-dipole-coupled excitation energy transfer can occur within the antigen-antibody complex. The resulting quenching of fluorescence can be inhibited by competitive binding with unlabeled antigen, Alternatively, separate antibody samples can be labeled with fluorescein and rhodamine, respectively. Unlabeled antigen causes aggregation of the separately labeled components with resultant quenching. Using the latter method, experiments suggest that up to about 20 anti-morphine antibody binding sites will associate with morphine-albumin conjugates. When an excess of the conjugate is present the antibodies appear to assemble in clumps on the protein surface. Mathematical analysis of the quenching of fluorescein-labeled morphine by rhodamine-labeled anti-morphine gives an approximate fit to the quenching data, but the calculations are very dependent on the assumptions used.
Activation of human blood coagulation factor XI independent of factor XII. (1991)

Human blood coagulation factor XI was activated by either autoactivation or thrombin. These reactions occurred only in the presence of negatively charged materials, such as dextran sulfate (approximately Mr 500,000), sulfatide, and heparin. During the activation, factor XI was cleaved at a single Arg-Ile bond by thrombin or factor XIa to produce an amino-terminal 50-kDa heavy chain and a carboxyl-terminal 35-kDa light chain. This activation pattern is identical to that produced by factor XIIa. The addition of a small amount of thrombin and sulfatide to factor XII-deficient plasma produced shorter clotting times than when these agents were added to factor XI/factor XII combined-deficient plasma. These results suggest that the activation of factor XI by thrombin and possibly the autoactivation of factor XI proceed in plasma to lead fibrin clot formation. These reactions may have a role on an appropriate negatively charged surface in normal hemostasis.
Computed Tomography Findings in Pathological Usual Interstitial Pneumonia (2007)

In patients with IPF and UIP pattern on the biopsy, the pattern of abnormality on thin-section CT, whether characteristic of UIP or suggestive of alternative diagnosis, does not influence prognosis. Prognosis is influenced by traction bronchiectasis and fibrosis scores.
Rizatriptan in migraine (2005)

The prevalence of migraine is high, affecting a significant proportion of the adult population during their most productive years of life and promoting impairment of their normal daily activities. Although guidelines for the acute treatment of migraine are available, outcome parameters are sometimes still below the expectations of both patients and physicians. Triptans represented an advance in clinical practice and have become the most well-studied class of medication for migraine. These agents present class I evidence for efficacy. However, they differ with regard to several of their clinical parameters, including onset of relief and consistency of response. Rizatriptan is a selective agonist of the 5-hydroxytryptophan(1B/1D )receptors, with proven superiority over placebo, ergotamine and selected oral triptans, demonstrating a good profile of safety and tolerability.
Structure, Orientation, and Conformational Changes in Transmembrane Domains of Multidrug Transporters (2004)

Multidrug transporter proteins promote the active transmembrane efflux of noxious drugs, thereby decreasing their accumulation in the intracellular medium and reducing their therapeutic efficiency. Expression of such proteins drastically reduces the efficiency of chemotherapeutic treatments against cancer and various infectious diseases. To overcome major difficulties related to the crystallization of membrane proteins, other experimental approaches have been developed to gain information on the structural changes involved in drug transport. We examine here and illustrate with a few examples how infrared and fluorescence spectroscopy can provide new insights into the structure of the membrane domains of multidrug transporters in particular. Such domains contain the drug-binding site(s) and mediate the passage of substrates across the cell membrane.
Application of Phosphoramidate Pronucleotide Technology to Abacavir Leads to a Significant Enhancement of Antiviral Potency (2005)

We report the first application of pronucleotide (ProTide) technology to the antiviral agent abacavir (Ziagen), used for the treatment of HIV infection. The phenylmethoxyalaninyl phosphoramidate of abacavir was prepared in good yield in one step. Also prepared was the corresponding phosphoramidate of the guanine nucleoside analogue "carbovir". The antiviral profile of each of the parent nucleosides was compared to that of the phosphoramidate ProTides. A significant (28- to 60-fold) increase in anti-HIV potency was noted for the ProTide of abacavir but not for that of carbovir. These findings were in agreement with the markedly higher (ca. 37-fold) levels of carbovir triphosphate that are formed in CEM cells upon response to the abacavir ProTide compared with the parent abacavir compound. In contrast the anti-HBV potency of both abacavir and carbovir were improved (10- and 20-fold, respectively) by ProTide formation. As in CEM cells, the abacavir ProTide provided significantly enhanced carbovir triphosphate levels in HepG2 2.2.15 cells over that of the parent nucleoside. On the basis of these data, a series of phosphoramidate analogues with structural variation in the ester and amino acid regions were prepared and their antiviral profiles described. In addition, the pharmacokinetic disposition of the abacavir phenylethoxyalaninyl phosphoramidate was evaluated in Cynomolgus monkeys.
The Role of Vascular Endothelial Growth Factor in Angiogenesis (2001)

Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen and an angiogenic inducer as well as a mediator of vascular permeability. The biological effects of VEGF are mediated by two tyrosine kinase receptors, Flt-1 (VEGFr-1) and KDR (VEGFR-2). VEGF is essential for developmental angiogenesis and is also required for female reproductive functions and endochondral bone formation. Substantial evidence also implicates VEGF in tumors and intraocular neovascular syndromes. Currently, several clinical trials are ongoing to test the hypothesis that inhibition of VEGF activity may be beneficial for these conditions.
Tamoxifen and metabolites in MCF7 cells: correlation between binding to estrogen receptor and inhibition of cell growth. (1982)

The binding of [3H]tamoxifen ([3H]Tam), a nonsteroidal antiestrogen, and of 4-[3H]hydroxytamoxifen ([3H]OH-Tam), a metabolite accumulated in vivo in target cell nuclei, was characterized in soluble extracts of human breast cancer MCF7 cells growing in a medium depleted in estrogens. Saturation analysis indicated a much higher affinity for OH-Tam (Kd = 0.15 nM) than for Tam (Kd = 4.8 nM). The binding of [3H]Tam and [3H]estradiol was competitive and mutually exclusive, and the binding site concentration (0.16 to 0.47 pmol/mg total protein) was similar for both ligands, strongly suggesting that antiestrogens were binding to the estrogen receptor (ER) in these cells. The ability of Tam and of some of its metabolites or derivatives to prevent the MCF7 cell growth was found to be correlated with their affinity for ER as determined by direct interaction or by binding competition with [3H]estradiol on the uterine and MCF7 cytosol ER. OH-Tam was the highest-affinity compound and was 100-fold more active than Tam. The inhibitions observed were actually due to Tam and OH-Tam, respectively, since we did not detect any significant metabolism of these two labeled compounds by the MCF7 cells. N-desmethyltamoxifen, the other Tam metabolites found in high concentration in human plasma, was as effective as Tam while cis-tamoxifen appeared less effective. Compound E, which has no lateral chain, was the only tested compound having a good affinity for ER and a poor efficiency in preventing cell growth. These results support the hypothesis that antiestrogens control the growth of breast cancer by acting directly on the ER located in cancer cells.
Phase I/Ib Study of Olaparib and Carboplatin in BRCA1 or BRCA2 Mutation-Associated Breast or Ovarian Cancer With Biomarker Analyses (2014)

Olaparib capsules 400mg every 12 hours on days 1 to 7/carboplatin AUC5 is safe and has activity in gBRCAm BrCa/OvCa patients. Exploratory translational studies indicate pretreatment tissue FOXO3a expression may be predictive for response to therapy, requiring prospective validation.
Comparison of Electronic Transport Measurements on Organic Molecules (2003)

Abstract We compile, compare, and discuss experimental results on low‐bias, room‐temperature currents through organic molecules obtained in different electrode–molecule–electrode test‐beds. Currents are normalized to single‐molecule values for comparison and are quoted at 0.2 and 0.5 V junction bias. Emphasis is on currents through saturated alkane chains where many comparable measurements have been reported, but comparison to conjugated molecules is also made. We discuss factors that affect the magnitude of the measured current, such as tunneling attenuation factor, molecular energy gap and conformation, molecule/electrode contacts, and electrode material.
Disulfide-bonded outer membrane proteins in the genus Legionella (1985)

Legionella pneumophila and related species were examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis for outer membrane proteins. Of the 10 species examined, 9 contained a 24-kilodalton (kDa) major outer membrane protein (MOMP) that was resolvable only when outer membrane material was heated in the presence of 2-mercaptoethanol. Labeling studies with [35S]cysteine indicated that the protein contained cysteine, and disulfide cross-linking of the unreduced complex was demonstrated by labeling with iodoacetamide. The unreduced outer membrane preparation contained peptidoglycan, and after treatment with lysozyme to remove peptidoglycan, a protein complex of 95 kDa was observed by sodium dodecyl sulfate polyacrylamide gel electrophoresis in the absence of 2-mercaptoethanol. Reduction of the 95-kDa complex yielded 24-kDa monomers, suggesting that the 95-kDa complex was composed of four subunits. The 24-kDa MOMP from L. pneumophila was purified, and antibody produced to this protein cross-reacted with all species of Legionella as determined from an immunoblot of a sodium dodecyl sulfate gel. Only serogroup 1 strains of L. bozemanii lacked the 24-kDa MOMP and showed no cross-reactivity. These results suggest that the 24-kDa MOMP common to most species of Legionella contains a genus-specific epitope.
N-t-Butoxycarbonyl Protection of Primary and Secondary Amines in the Hydroboration Reaction: Synthesis of Amino Alcohols (1995)

Abstract The use of the BOC group as a protecting group in the hydroboration of aminoalkenes is described. The isolated yields of amino alcohols via the hydroboration-oxidation sequence are excellent.
Antigenic Domains of the HIV-1 vif Protein as Recognized by Human Sera and Murine Monoclonal Antibodies (1991)

To analyze the vif antibody response in individuals infected with the human immunodeficiency virus type 1 (HIV-1) and to determine antigenic epitopes on the vif protein, 104 HIV-1+ sera were screened for reactivity with a recombinant vif protein; 30 (28.8%) of these sera recognized the recombinant vif protein in immunoblot and were employed, together with 17 HIV-1/vif-negative control sera, in an enzyme immunoassay (EIA)-based epitope scanning assay with 183 overlapping decapeptides that covered the complete amino acid sequence of the HIV-1 vif protein (strain BH10). Of the 30 HIV-1/vif+ sera, 87% reacted with decapeptides comprising the two following epitopes: IEWRKKRY (vif amino acids 87-94) or DRWNKPQ (vif amino acids 172-178). The two epitopes were 89% and 100% conserved among different HIV-1 strains and their antigenicity could be confirmed by computer-assisted predictions of vif antigenic determinants. All the sera reactive with recombinant vif protein and with vif peptides originated from patients in CDC stages III or IV. Two murine anti-vif monoclonal antibodies reacted only with the seven C-terminal amino acids of the vif protein (SHTMNGH), which were not recognized by any of the human sera. Our results may be useful for further studies of vif seroreactivity and for the production of anti-vif mono- or polyclonal antibodies using vif peptides.
Purification and regulation of mevalonate kinase from rat liver. (1990)

Mevalonate kinase may play a key role in regulating cholesterol biosynthesis because its activity may be regulated via feedback inhibition by intermediates in the cholesterol biosynthetic pathway. To study the regulation of mevalonate kinase, the enzyme was purified to homogeneity from rat liver, and monospecific antibody against mevalonate kinase was prepared. The purified mevalonate kinase had a dimeric structure composed of identical subunits, and the Mr of the enzyme determined by gel chromatography was 86,000. Based on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the subunit Mr was 39,900. The pI for mevalonate kinate was 6.2. The levels of mevalonate kinase protein and enzyme activity were determined in the livers of rats treated with either cholesterol-lowering agents (cholestyramine, pravastatin, and lovastatin) or with dietary modifications. Diets containing cholestyramine alone or cholestyramine and either pravastatin or lovastatin increased mevalonate kinase activity 3-6-fold. Mevalonate kinase activity decreased approximately 50% in rats treated with diets containing either 5% cholesterol or 5% cholesterol and 0.5% cholic acid. Fasting did not significantly change mevalonate kinase activity. The amount of mevalonate kinase protein in the liver was quantitated using immunoblots, and the changes in the levels of kinase activity induced by either drug treatment or by cholesterol feeding were correlated with similar changes in the levels of mevalonate kinase protein. Therefore, under these experimental conditions, mevalonate kinase activity in the liver was regulated principally by changes in the rates of enzyme synthesis and degradation.
Binding and Kinetics for Molecular Biologists (2006)

1. Performing quantitative experiments with biomolecules 2. Affinity constants 3. Cooperativity in binding 4. Rate constants for binding and dissociation 5. Kinetics of regulation and cooperativity in binding Reactions 6. Constants for a two-step binding reaction 7. Data analysis Appendix 1: Equation derivations Appendix 2: Resources and references Index
On the Regulation of Gene Activity (1961)

According to modern concepts, the deoxynucleotide sequence which constitutes a gene participates in two distinct chemical processes. In the first, for which the term replication should be reserved, free deoxyribonucleotides are linearly assembled by specific base-pairings, forming an identical sequence or replica of the original sequence; the second process, which we shall call transcription, allows the gene to perform its physiological function, i.e., to specify the molecular structure of a certain protein or polypeptide chain. Transcription does not appear to be a direct process, since it most probably involves the formation of an intermediate as carrier of the genetic information. Two stages may then be distinguished in transcription, the first of which is presumably closely similar to replication, involving, however, ribonucleotides instead of deoxynucleotides, and resulting in an RNA "transcript" of the original DNA sequence. In the second transcription stage, the RNA transcript in turn directs the assembly of...
Purification and Characterization of Acid Phosphatases with or without Phytase Activity from Rice Bran (1989)

Journal Article Purification and Characterization of Acid Phosphatases with or without Phytase Activity from Rice Bran Get access Toshiro Hayakawa, Toshiro Hayakawa Department of Agricultural Chemistry, Faculty of Agriculture, Niigata University, Ikarashi 2–8050, Niigata 950—21, Japan Search for other works by this author on: Oxford Academic Google Scholar Yoshiaki Toma, Yoshiaki Toma Department of Agricultural Chemistry, Faculty of Agriculture, Niigata University, Ikarashi 2–8050, Niigata 950—21, Japan Present addressHoechst Japan Limited, Sapporo 060, Japan. Search for other works by this author on: Oxford Academic Google Scholar Ikuo Igaue Ikuo Igaue Department of Agricultural Chemistry, Faculty of Agriculture, Niigata University, Ikarashi 2–8050, Niigata 950—21, Japan Search for other works by this author on: Oxford Academic Google Scholar Agricultural and Biological Chemistry, Volume 53, Issue 6, 1 June 1989, Pages 1475–1483, https://doi.org/10.1080/00021369.1989.10869506 Published: 01 June 1989 Article history Received: 19 October 1988 Published: 01 June 1989
An Observational Study of Circulating Tumor Cells and 18F-FDG PET Uptake in Patients with Treatment-Naive Non-Small Cell Lung Cancer (2013)

CTCs are detected frequently in early-stage NSCLC using a non-EpCAM mediated approach with a wide range noted for a given level of FDG uptake or tumor size. Integrating potentially complementary biomarkers like these with traditional patient data may eventually enhance our understanding of clinical, in vivo tumor biology in the early stages of this deadly disease.
The SSX gene family: Characterization of 9 complete genes (2002)

Human SSX genes comprise a gene family with 6 known members. SSX1, 2 and 4 have been found to be involved in the t(X;18) translocation characteristically found in all synovial sarcomas. Four (SSX1, 2, 4 and 5) are known to be expressed in a subset of tumors and testis, and anti-SSX antibodies have been found in sera from cancer patients. SSX antigens are thus typical cancer-testis (CT) antigens. To identify additional SSX family members, we isolated and characterized human genomic clones homologous to a prototype SSX cDNA. We also searched public databases for sequences similar to SSX. This identified 3 additional SSX genes, SSX7, 8, 9, and also completed the sequence of the formerly partially defined SSX6 gene. In addition to these novel SSX genes, several SSX pseudogenes were identified. With the exception of 1 pseudogene, all SSX genomic SSX sequences map to chromosome X. Among normal tissues, SSX7 mRNA was present only in testis, whereas SSX6, 8 and 9 were not detected in any normal tissue. SSX6 and 7 were expressed in 1 of 9 melanoma cell lines tested, whereas SSX8 and 9 expression was not detected in any tumor tissue or cell lines tested. SSX1, 2, 4 and 5 mRNA expression can be induced in cell lines by 5-aza-2-deoxycytidine or Trichostatin A. These agents also induce SSX6, but not SSX3, 7, 8 or 9 in the tumor cell lines tested, indicating that mechanisms other than methylation or histone acetylation may be responsible for the repressed state of some SSX genes.