gebhart/patrepeval huggingface dataset:
p-Toluensulfonic Acid and Cation Exchange Resin in Aprotic Solvent: Valuable Catalysts for Fischer Indolization (1984)

p-Toluenesulfonic acid and cation exchange resin (Amberlyst-15) in aprotic solvent were found to serve as a good catalyst for Fischer indolization in many cases.With this condition ethyl indole-2-carboxylate was prepared more conveniently in better yield than by previous methods.Fischer indolizationla is the most valuable and widely-used method for synthesis of indoles, and thus numerous combination of mineral, organic, or Lewis acids with various solvents have been developedlb for the catalyst.However, there have not been so many examples lb" reported for the usage of aprotic solvents.We now wish to report that p-toluenesulfonic acid (TsOH) and cation exchange resin (Amberlyst-15) in aprotic solvent (benzene or toluene) have some advantages for practical synthesis of various indoles by Fischer indolization. 3In connection with our synthetic studies we needed a large amount of ethyl indole-2-carboxylate ( & ) , which is a stable equivalent of indole itself.Although the Reissert method is considered4 as a standard one for preparing the indole (1).the yield is neither satisfactory nor the procedure is necessarily convenient because of the use of dangerous metal potassium.We reinvestigated the Fischer indolization of ethyl pyruvate 2-(phenylhydrazone) (2) for the facile and improved preparation of the indole I&), as Fischer indolization is suitable for laboratory large scale experiment because of its easy-handling procedure.At first we tried the Fischer indolization of the phenylhydrazone (2) with H2S04/ ACOH as reported.'However, this reaction afforded the indole (1) in only 38.8% Yield.accompanied with ethyl 2-(2-ethoxycarbonylindol-3-y1)acrylate ()_) in 5.9%
Dosage Adjustment and Pharmacokinetic Profile of Irinotecan in Cancer Patients With Hepatic Dysfunction (2002)

We showed that baseline total bilirubin level could be used to determine the appropriate dose of irinotecan in cancer patients with hepatic dysfunction. Doses of 350 mg/m(2) and 200 mg/m(2) were considered RDs in patients with bilirubin values <or= 1.5 times ULN and 1.51 to 3.0 times ULN, respectively.
The dependence of calcium-activated potassium currents on membrane potential (1992)

Previous experiments on cholinergic synapses in chick cochlear hair cells have shown that calcium entering through acetylcholine-activated synaptic channels in turn activates calcium-dependent potassium currents, resulting in synaptic inhibition. In voltage-clamp experiments such currents would be expected to increase with depolarization (as the driving force for potassium entry is increased) and then decrease towards zero as the membrane approaches the calcium equilibrium potential (when calcium entry is suppressed). In the hair cells, however, such currents approached zero at about +20 mV, more than 170 mV negative to the calcium equilibrium potential. Another feature of the synapse is its post-junctional morphology: a uniform 20 nm cleft is formed between the postsynaptic membrane and the outermost membrane of an underlying cisterna. Here we present a model in which synaptic activation results in calcium influx into the subsynaptic cleft and thence into the bulk of the cytoplasm. The model suggests that the voltage dependence of the calcium-activated potassium current can be accounted for by only two basic assumptions: (i) entry of calcium through the activated synaptic channels by simple diffusion; and (ii) activation of the potassium channels by the cooperative action of four calcium ions. In addition, the model suggests that during activation the calcium concentration in the restricted subsynaptic space can reach levels adequate to activate the potassium channels, without requiring additional, more complicated, considerations (for example, secondary calcium release from the cisterna).
Botulinum toxin type A in the treatment of focal, axillary and palmar hyperhidrosis and other hyperhidrotic conditions (1999)

Focal essential hyperhidrosis is a common and often disabling disorder mainly involving the palms, axillae, face, and soles of the feet. Focal hyperhidrosis may also arise from several neurological or internal diseases. Current therapeutic options include topical aluminium chloride salts, systemic anticholinergic drugs, tap‐water iontophoresis, and a number of surgical approaches. However, none of these are entirely satisfactory. In recent studies, injection of botulinum toxin type A (BTX‐A) into the hyperhidrotic area has proved very effective in reducing or abolishing focal sweating of different aetiologies without major side effects. BTX‐A therefore has the potential to replace more invasive therapies.
Location of the major antigenic sites involved in rotavirus serotype-specific neutralization. (1986)

Antigenic sites on the rotavirus major outershell glycoprotein were identified by using mutant viruses selected for resistance to neutralizing (serotype-specific) monoclonal antibodies. The glycoprotein genes from these mutants were sequenced to determine the position and nature of the resultant amino acid substitutions in the protein. Three regions (A, B, and C) were identified (amino acids 87-96, 145-150, and 211-223, respectively), of which region C appears to be the most important. A mutation in region C caused a 10-fold increase in resistance to neutralization by polyclonal antiviral antiserum. The results of this study, together with other data, indicate that the three-dimensional folding of the native protein is such that regions A and C are in close proximity.
Potentiation by the hypoxic cytotoxin SR 4233 of cell killing produced by fractionated irradiation of mouse tumors. (1990)

The new bioreductive drug 3-amino-1,2,4-benzotriazine 1,4-dioxide (SR 4233) shows a high selective cytotoxicity for hypoxic cells, both in vitro and in tumors in vivo. In the present experiments, we have tested the hypothesis that this selective killing of hypoxic cells might be exploited by taking advantage of the fluctuating hypoxia in tumors by use of a multidose regimen of SR 4233 with multiple small doses of X-rays. We have tested four different transplantable mouse tumors using a standard fractionated protocol of 8 x 2.5 Gy in 4 days, using a well tolerated dose of SR 4233 given with each radiation dose. All of the tumors showed a substantial enhancement of cell killing by SR 4233 over that produced by radiation alone with dose-modifying factors of 1.5 to 3.0 for the different tumors. In all four tumors, the enhancement of cell killing was greater than that produced by a large dose of the hypoxic cell sensitizer SR 2508 given before each irradiation, thereby demonstrating the superiority of the approach of using a hypoxic cytotoxic agent rather than a radiosensitizer in fractionated radiation protocols. The data suggest that SR 4233 has considerable promise as an adjunct to standard radiotherapy.
Magnetic Microspheres Prepared by Redox Polymerization Used in a Cell Separation Based on Gangliosides (1978)

A facile method is described for making magnetic microspheres that bind specifically to cell surfaces, in order to separate cells magnetophoretically. Control over the sizes of the spheres is effected by using their magnetic cores as part of a redox polymerization system. The use of the microspheres is demonstrated with a separation involving C-1300 neuroblastoma cells, 10% of which express the ganglioside GM1 in their membranes. The GM1-containing cells were separated with better than 99% purity, while the deficient cells were obtained at least 98% pure. The separation, which was carried out under sterile conditions, required only 6 minutes.
Interspecies spleen-myeloma hybrid producing monoclonal antibodies against mouse lymphocyte surface glycoprotein, T200. (1978)

A cell hybrid has been selected from fusion of a mouse myeloma and rat spleen cells immunized against mouse lymphoma cells that produces monoclonal antibody against the mouse lymphocyte surface glycoprotein, T200. Antibody binding assays employing the monoclonal antibody show that there are about 50,000-100,000 molecules of T200 glycoprotein on mouse thymocytes and that similar antigens are present on spleen and bone marrow but not detected on nonlymphoid tissues. Examination of the labeled molecules precipitated from detergent extracts of spleen cells and thymocytes iodinated by the lactoperoxidase technique by SDS-PAGE confirm that there are structural differences between the antigens found on B and T lymphocytes. The B-cell glycoprotein consists of at least one component of apparent mol wt 220,000 on SDS-PAGE, while the T-cell glycoprotein has an apparent mol wt of about 190,000.
Functional expression and release of ligands for the activating immunoreceptor NKG2D in leukemia (2003)

Abstract NKG2D ligands (NKG2DLs) mark malignant cells for recognition by natural killer (NK) cells and cytotoxic T lymphocytes via the activating immunoreceptor NKG2D. This led to the hypothesis that NKG2DLs play a critical role in tumor immune surveillance. The human NKG2DLs MICA and MICB are expressed on tumors of epithelial origin in vivo. For the other recently described set of human NKG2DLs, the UL16-binding proteins (ULBPs), expression in vivo is as yet undefined. In this study we investigated expression and function of NKG2DLs in leukemia using a panel of newly generated NKG2DL-specific monoclonal antibodies. We report that leukemia cells from patients variously express MIC and ULBP molecules on the cell surface with MICA most frequently detected. Patient leukemia cells expressing MICA were lysed by NK cells in an NKG2D-dependent fashion. Sera of patients, but not of healthy donors, contained elevated levels of soluble MICA (sMICA). We also detected increased sMICB levels in patient sera using a newly established MICB-specific enzyme-linked immunosorbent assay. Reduction of leukemia MIC surface expression by shedding may impair NKG2D-mediated immune surveillance of leukemias. In addition, determination of sMICA and sMICB levels may be implemented as a prognostic parameter in patients with hematopoietic malignancies.
A Boundary Hunting Radial Basis Function Classifier which Allocates Centers Constructively (1992)

A new boundary hunting radial basis function (BH-RBF) classifier which allocates RBF centers constructively near class boundaries is described. This classifier creates complex decision boundaries only in regions where confusions occur and corresponding RBF outputs are similar. A predicted square error measure is used to determine how many centers to add and to determine when to stop adding centers. Two experiments are presented which demonstrate the advantages of the BH-RBF classifier. One uses artificial data with two classes and two input features where each class contains four clusters but only one cluster is near a decision region boundary. The other uses a large seismic database with seven classes and 14 input features. In both experiments the BH-RBF classifier provides a lower error rate with fewer centers than are required by more conventional RBF, Gaussian mixture, or MLP classifiers.
Carotenoids and related compounds. Part XIV. Stereochemistry and synthesis of geraniol, nerol, farnesol, and phytol (1966)

The cis- and trans-structures assigned to nerol and geraniol respectively have been confirmed.The trans, trans-structure of the common form of farnesol, and of the farnesyl pyrophosphate involved in the biosynthesis of squalene, has been rigorously established.Phytol has been shown to have a trans-configuration about the double bond, and an R-configuration at both asymmetric centres.
Expression of the c‐erbB‐3 gene product in gastric cancer (1993)

The pattern of c-erbB-3 gene product was studied in 91 advanced gastric carcinomas, adjacent hyperplastic mucosa, intestinal metaplasia and dysplasia and in normal controls, using immunohistochemistry in archival material. All tumours showed positive c-erbB-3 staining in both cytoplasm and membrane. No significant differences of expression were observed between intestinal and diffuse-type carcinomas or any other clinical parameters. Of interest is the expression in the adjacent mucosa, which is extensive, cytoplasmic, and of lower intensity than in the tumours. Further studies are currently being carried out to clarify the role of this protein in tumour behaviour and gastric carcinogenesis.
TransMabs: cell-penetrating antibodies, the next generation (2005)

Intracellular proteins are becoming attractive targets in diagnosis and for therapy such as in signal pathways, on enzymes, transcription factors and structural proteins. Antibodies have been used therapeutically for extracellular pathogens and for targeting cell-surface antigens. Antibodies normally do not pass easily through intact cellular or subcellular membranes in living cells. Methods to shuttle antibodies into living cells are either labour-intensive and/or compromise the structural and functional integrity of the cell or require the integration of genes for heavy and light chain production through gene therapy approaches. A new technology platform, 'SuperAntibody Technology', enables antibodies to be shuttled into living cells without harming them. Such cell-penetrating antibodies open new diagnostic and therapeutic windows. The term 'TransMabs' has been coined for these antibodies. Proof of principle has been achieved with a 17-amino acid peptide with membrane translocating properties, conjugated with anti-caspase-3 antibody. Such a TransMab inhibits significantly in vitro apoptosis-related events, such as caspase-3 activity, DNA fragmentation and spectrin cleavage. Anti-caspase-3 TransMab, therefore, could be utilised to inhibit apoptosis in a variety of diseases, such as Alzheimer's, Huntington's and Parkinson's. Unlike peptide inhibitors available at present, this TransMab is not expected to have invivo toxic side effects and can only target activated forms of the enzyme. This paper discusses the advantages and limitations of cell-penetrating antibodies (TransMabs) compared with existing small molecule drug development approaches.
Isolation and characterization of a heparin-binding domain from the amino terminus of platelet thrombospondin. (1984)

Calcium-replete thrombospondin has been purified from outdated platelets using heparin-Sepharose affinity chromatography, gelatin-Sepharose to remove fibronectin, and gel filtration to eliminate low-molecular-weight heparin-binding proteins. Edman degradation of six different preparations revealed the amino-terminal sequence of thrombospondin (TSP) to be Asn-Arg-Ile-Pro-Glu-Ser-Gly-Gly-Asp-Asn-Ser-Val-Phe-. This sequence was obtained in initial yields as high as 85%, indicating that no blocked chains are present. Cleavage of calcium-replete TSP with thermolysin or plasmin results in the production of relatively stable fragments. Chromatography of these digests on heparin-Sepharose followed by elution with 0.6 M NaCl affords purification of an Mr 25,000 fragment from the thermolysin digest and an Mr 35,000 fragment from the plasmin digest. The binding of these fragments to heparin-Sepharose does not require divalent metal ions. Neither fragment is disulfide-bonded to other fragments present in the digests. The heparin-binding domains from both digests have similar amino acid compositions and their tryptic peptide maps on high performance liquid chromatography are identical with the exception of one peptide unique to each fragment. Automated Edman degradation in a vapor-phase sequenator of the thermolytic heparin-binding domain electroeluted from sodium dodecyl sulfate-gels indicates that the heparin-binding domain resides at the amino terminus of the Mr 180,000 TSP peptide chain.
Colic. (1989)

Colic begins between the second and sixth week of life and usually abates by the fourth month of life. Crying may occur any time of the day but is most common after the evening feeding. Removal of cow's-milk protein from the diet eliminates colic in 30 percent of infants. Simethicone and an antispasmodic agent are sometimes helpful.
Endosomal Proteolysis of the Ebola Virus Glycoprotein Is Necessary for Infection (2005)

Ebola virus (EboV) causes rapidly fatal hemorrhagic fever in humans and there is currently no effective treatment. We found that the infection of African green monkey kidney (Vero) cells by vesicular stomatitis viruses bearing the EboV glycoprotein (GP) requires the activity of endosomal cysteine proteases. Using selective protease inhibitors and protease-deficient cell lines, we identified an essential role for cathepsin B (CatB) and an accessory role for cathepsin L (CatL) in EboV GP-dependent entry. Biochemical studies demonstrate that CatB and CatL mediate entry by carrying out proteolysis of the EboV GP subunit GP1 and support a multistep mechanism that explains the relative contributions of these enzymes to infection. CatB and CatB/CatL inhibitors diminish the multiplication of infectious EboV-Zaire in cultured cells and may merit investigation as anti-EboV drugs.
Clinically Approved Heterocyclics Act on a Mitochondrial Target and Reduce Stroke-induced Pathology (2004)

Substantial evidence indicates that mitochondria are a major checkpoint in several pathways leading to neuronal cell death, but discerning critical propagation stages from downstream consequences has been difficult. The mitochondrial permeability transition (mPT) may be critical in stroke-related injury. To address this hypothesis, identify potential therapeutics, and screen for new uses for established drugs with known toxicity, 1,040 FDA-approved drugs and other bioactive compounds were tested as potential mPT inhibitors. We report the identification of 28 structurally related drugs, including tricyclic antidepressants and antipsychotics, capable of delaying the mPT. Clinically achievable doses of one drug in this general structural class that inhibits mPT, promethazine, were protective in both in vitro and mouse models of stroke. Specifically, promethazine protected primary neuronal cultures subjected to oxygen-glucose deprivation and reduced infarct size and neurological impairment in mice subjected to middle cerebral artery occlusion/reperfusion. These results, in conjunction with new insights provided to older studies, (a) suggest a class of safe, tolerable drugs for stroke and neurodegeneration; (b) provide new tools for understanding mitochondrial roles in neuronal cell death; (c) demonstrate the clinical/experimental value of screening collections of bioactive compounds enriched in clinically available agents; and (d) provide discovery-based evidence that mPT is an essential, causative event in stroke-related injury.
Virtual Environments and Dyslexia: A Literature Review (2014)

This study is a critical review of published scientific literature on the use of Virtual Reality and its applications in developmental dyslexia. The purpose of this research is to: (a) present a synthesis of the available empirical evidence, (b) identify the potential contribution of Virtual Environments (VEs) in the disorder's screening, intervention, awareness process and assessment, and (c) define future research perspectives concerning the applications of VEs in this particular research field. The results show that the research in the field focuses on: (a) visuospatial skills, (b) nonverbal problem skills, (c) memory performance, and (d) awareness increase for dyslexia. The majority of the articles found are pilot or small-scale studies that can only provide indications on the VEs and their beneficial results, but can provide useful guidance for researchers, educators, practitioners and parents.
RNA Interference Reveals that Ligand-Independent Met Activity Is Required for Tumor Cell Signaling and Survival (2004)

Hepatocyte growth factor/scatter factor-Met signaling has been implicated in tumor growth, invasion, and metastasis. Suppression of this signaling pathway by targeting the Met protein tyrosine kinase may be an ideal strategy for suppressing malignant tumor growth. Using RNA interference technology and adenovirus vectors carrying small-interfering RNA constructs (Ad Met small-interfering RNA) directed against mouse, canine, and human Met, we can knock down c-met mRNA. We show a dramatic dependence on Met in both ligand-dependent and ligand-independent mouse, canine, and human tumor cell lines. Mouse mammary tumor (DA3) cells and Met-transformed NIH3T3 (M114) cells, as well as both human and canine prostate cancer (PC-3 and TR6LM, human sarcoma (SK-LMS-1), glioblastoma (DBTRG), and gastric cancer (MKN45) cells, all display a dramatic reduction of Met expression after infection with Ad Met small-interfering RNA. In these cells, we observe suppression of tumor cell growth and viability in vitro as well as inhibition of hepatocyte growth factor/scatter factor-mediated scattering and invasion in vitro, whether Met activation was ligand dependent or not. Importantly, Ad Met small-interfering RNA led to apoptotic cell death in many of the tumor cell lines, especially DA3 and MKN45, but did not adversely affect MDCK canine kidney cells. Met small-interfering RNA also abrogated downstream Met signaling to molecules such as Akt and p44/42 mitogen-activated protein kinase. We further show that intratumoral infection with c-met small-interfering RNA adenovirus results in a substantial reduction in tumor growth. Thus, Met small-interfering RNA adenoviruses are reliable tools for studying Met function and raise the possibility of their application for cancer therapy.
Role of Nucleoporin Induction in Releasing an mRNA Nuclear Export Block (2002)

Signal-mediated nuclear import and export proceed through the nuclear pore complex (NPC). Some NPC components, such as the nucleoporins (Nups) Nup98 and Nup96, are also associated with the nuclear interior. Nup98 is a target of the vesicular stomatitis virus (VSV) matrix (M) protein-mediated inhibition of messenger RNA (mRNA) nuclear export. Here, Nup98 and Nup96 were found to be up-regulated by interferon (IFN). M protein-mediated inhibition of mRNA nuclear export was reversed when cells were treated with IFN-gamma or transfected with a complementary DNA (cDNA) encoding Nup98 and Nup96. Thus, increased Nup98 and Nup96 expression constitutes an IFN-mediated mechanism that reverses M protein-mediated inhibition of gene expression.
A density-based algorithm for discovering clusters a density-based algorithm for discovering clusters in large spatial databases with noise (1996)

Clustering algorithms are attractive for the task of class identification in spatial databases. However, the application to large spatial databases rises the following requirements for clustering algorithms: minimal requirements of domain knowledge to determine the input parameters, discovery of clusters with arbitrary shape and good efficiency on large databases. The well-known clustering algorithms offer no solution to the combination of these requirements. In this paper, we present the new clustering algorithm DBSCAN relying on a density-based notion of clusters which is designed to discover clusters of arbitrary shape. DBSCAN requires only one input parameter and supports the user in determining an appropriate value for it. We performed an experimental evaluation of the effectiveness and efficiency of DBSCAN using synthetic data and real data of the SEQUOIA 2000 benchmark. The results of our experiments demonstrate that (1) DBSCAN is significantly more effective in discovering clusters of arbitrary shape than the well-known algorithm CLAR-ANS, and that (2) DBSCAN outperforms CLARANS by a factor of more than 100 in terms of efficiency.