gebhart/patrepeval huggingface dataset:
Cell Surface Transmembrane Protein Database for Detecting Potential Targets of Antibody Drug in Application of Cancer Therapies (2010)

Background: Antibody drug conjugated (ADC) is one kind of very important method of therapy to cancer diseases. In this research, the authors introduce BLAST and some other important algorithms to create transmembrane protein databases. These databases are acquired from well-known databases such as NCBI or Swiss-Prot as template, and then collect all possible transmembrane protein by using BLAST or physical character. After collect these databases, the authors will aim at each nucleotide sequences to design the probes of oligonucleotide microarray, which can detect the high express transmembrane proteins very efficiently. Finally, the authors can accelerate the anti-cancer drug discovery by using these databases. Result: This study constructed a web service, the Transmembrane Protein Database, to researchers that are interested in or need to oligonucleotide microarray probe design for detecting potential targets of antibody drug. With user friendly web based windows containing each necessary selections, users can easily choose the parameters and get the suitable probe design suggestions. Conclusion: Transmembrane protein database is very important and powerful in detecting cancers or other human disease. By using this database, the authors offer a good strategy in transmembrane protein research as well.
Down-regulation of Notch1 or Notch3 can decrease the migration and invasion of HepG2 and MHCC97H cells in vitro. (2015)

&lt;p&gt;(a–c) Migrated HCC cells analyzed by transwell assays compared with siRNA controls. (d–f) Invaded HCC cells analyzed by transwell assays compared with siRNA controls. The data are presented as the mean ± SD, *P&lt;0.05 compared with control siRNA-transfected HepG2 cells; #P&lt;0.05 compared with control siRNA-transfected MHCC97H cells. NT: No transfection; Cs: control siRNA transfection; N1s: Notch1 siRNA transfection; N3s: Notch3 siRNA transfection.&lt;/p&gt;
Palladium‐Catalyzed Vicinal Difunctionalization of Internal Alkenes: Diastereoselective Synthesis of Diamines (2012)

Internal affairs: the first general palladium-catalyzed intermolecular diamination of internal alkenes employs different nitrogen sources, which add to the alkene in a regio- and diastereoselective fashion. The resulting diamination products can be converted directly into a known ligand motif.
Beyond Trastuzumab: Small Molecule Tyrosine Kinase Inhibitors in HER-2–Positive Breast Cancer (2009)

HER-2 is a transmembrane, tyrosine kinase (TK) receptor whose overexpression is associated with adverse prognosis in breast cancer. The biological effects of HER-2 are mediated by kinase activity causing phosphorylation of tyrosine residues in the cytoplasmic domain of the receptor molecule, leading to activation of downstream growth-promoting pathways. Antibody-mediated inhibition by trastuzumab as well as TK inhibition are clinically effective anti-HER-2 strategies. Kinase inhibitors offer some potential therapeutic advantages over antibody-based therapies. Being small molecules, TK inhibitors (TKIs) have oral bioavailability and ability to cross the blood-brain barrier. Because of their different mode of action, TKIs may be able to overcome some of the mechanisms of trastuzumab resistance. Preclinical, and limited clinical data also suggest that TKIs and trastuzumab have synergistic activity. Lapatinib is the only TKI available for clinical use at present, but several molecules with anti-HER-2 activity have been identified and are undergoing evaluation. These differ in the spectrum of kinases that they inhibit, potency of HER-2 inhibition, pharmacokinetic properties, and toxicity profiles, and are at various stages of clinical development. In this article we summarize selected HER-2 TKIs approved for clinical use or in development for which clinical data are available.
Mapping inter-regional connectivity of the entire cortex to characterize major depressive disorder (2012)

Diffusion tensor imaging (DTI) can be used to study the organization of brain white matter noninvasively. The aim of this study was to present a proof of concept for integrating DTI with high-resolution anatomical (T1) images to map and assess inter-regional connectivity across the entire cortex in a cohort of healthy participants and compared with patients with major depressive disorder. We used MRI data of 23 patients and 23 matched controls, assessed as part of baseline testing in the International Study to Predict Optimized Treatment in Depression (iSPOT-D). Freesurfer was used to analyze the T1 images to automatically label 35 gyral-based areas for each hemisphere. DTI tractography was performed to parcellate intercortical tracts using each of these areas in seed-target combinations. We quantified fractional anisotropy, number-of-fiber connections, and fiber path length for each DTI connection, with the goal of identifying the best measure or combination of measures to characterize major depression. The best classification accuracy for the individual measures was achieved using the number-of-fibers data, whereas the combination model provided a slight improvement. The most discriminant features between the two groups were for white matter associated with the limbic, frontal, and thalamic projection fibers and as part of cortical connections between the left inferior temporal and the postcentral cortex; the left parstriangularis and the left superior frontal; the left cuneus and the corpus callosum; the left lingual and the right lateral occipital, the right superior parietal and the right superior temporal cortices; and the right inferior parietal and the right insula and postcentral cortices.
Remote MIB-item look-up service (2003)

Despite some deficiencies, the Internet management framework is widely deployed and thousands of management information base (MIB) modules have been defined thus far. These modules are used by implementers of agent software, as well as by managers and management applications, to understand the syntax and semantics of the management information that may be exchanged. At the manager's side, MIB modules are usually stored in separate files, which are maintained by the human manager and read by the management application. Since maintenance of this file repository can be cumbersome, management applications are often confronted with incomplete and outdated information. To solve this "meta-management" problem, this paper discusses the design of a remote look-up service for MIB-item definitions. Such a service facilitates the retrieval of missing MIB module definitions, as well as definitions of individual MIB-items. Initially the service may be provided by a single server, but other servers can be added at later stages to improve performance and prevent copyright problems. It is envisaged that vendors of network equipment will also install servers, to distribute their vendor specific MIB. The paper describes how the service, which is provided on a best effort basis, can be accessed by managers/management applications, and how servers inform each other about the MIB modules they support.
Lineare Gleichungssysteme (2011)

Lineare Gleichungssysteme bilden in mindestens dreifacher Hinsicht ein Kernstück der Linearen Algebra:
Polymorphism in the serotonin transporter gene and response to treatment in African American cocaine and alcohol‐abusing individuals (2005)

The serotonin transporter (5-HTT) regulates serotonin transmission and modulates behavioral effects of drug of abuse. A polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) yielding a short (S) and long (L) allele has been associated with severity of substance abuse. The aims of the study were to investigate whether 5-HTTLPR genotypes differed in their response to treatment in cocaine- and alcohol-abusing patients. Polymerase chain reaction-based genotyping of a 44 base pair insertion/deletion polymorphism was performed in 141 African American cocaine-dependent patients with concurrent alcohol use who were entering a 12-week behaviorally oriented outpatient treatment program. In treatment, end of treatment and 6-month follow-up outcome measures included changes in Addiction Severity Index (ASI) scores, urine drug screens, days in treatment, individual/group sessions, dropout and completion rates. As expected, there was a reduction in substance abuse by the end of treatment and follow-up (F = 5.15, p = 0.000). However, there were no differences in the reduction in cocaine use across the LL, LS and SS genotypes. Interestingly, individuals with the S allele showed greater severity of alcohol use at admission (F = 4.84, p = 0.03), and the SS genotype showed less improvement in alcohol measures than the LL at follow-up (F = 3.68, p = 0.03), after controlling for baseline variables. While we found no association of the 5-HTTLPR variants with severity of cocaine abuse or any cocaine-related outcome measures, the data suggested that the 5-HTTLPR polymorphism may distinguish responders from non-responders to behavioral treatment in terms of alcohol use. Further investigations are required to determine the role of the 5-HTTLPR polymorphism in influencing treatment - outcome among substance abusers.
Optimization of a Reverse Transcription-Polymerase Chain Reaction (RT-PCR) Mass Assay for Low-Abundance mRNA (1998)

Whereas Northern analysis is a standard procedure by which abundant levels of mRNA can be quantified and characterized by size, there is a limit to the sensitivity of this technique, even with the best probes and the use of poly(A+) mRNA enrichment (see Chapters 28 and 30). At these times, it is necessary to move to more sensitive techniques. RNase protection assays or equivalent are much more sensitive but are technically difficult to perform, and require expensive dedicated equipment as well as production of riboprobes. More recently, there has been a predominance of the use of equally sensitive reverse transcription-polymerase chain reaction (RT-PCR) methodologies, which rely on the now more universally available PCR cycler and otherwise inexpensive and easily performed Southern Blot analytical methodology.
A novel patatin‐like gene stimulated by drought stress encodes a galactolipid acyl hydrolase (2001)

A cDNA (Vupat1) encoding a predicted 43 kDa protein was isolated from drought-stressed cowpea (Vigna unguiculata) leaves. It has homology with patatin, a potato tuber storage protein with lipolytic acyl hydrolase activity. The recombinant protein VUPAT1 expressed in the baculovirus system displays preferentially galactolipid acyl hydrolase activity. Phospholipids are very slowly hydrolyzed and apparently triacylglycerols are not deacylated. Vupat1 promoter contains putative drought-inducible sequences. Northern blots showed that gene expression is stimulated by drought stress and is more pronounced in a drought-sensitive cultivar than in a drought-tolerant one. An involvement in drought-induced galactolipid degradation is proposed for VUPAT1.
In vitro modulating effect of the reversible protein synthesis inhibitor zilascorb (2H) on cis-diamminedichloroplatinum (II)-induced cytotoxicity. (1992)

Zilascorb (2H) (5,6-benzylidene-d1-L-ascorbic acid sodium salt), a derivative of deuterated benzaldehyde inducing reversible protein synthesis inhibition, was tested on human NHIK 3025 cells in combination with the anticancer drug cis-diamminedichloroplatinum(II) (cis-DDP). The inactivating effect of cis-DDP, measured as loss of colony forming ability, was found to increase when a non-toxic treatment with zilascorb (2H) was given simultaneously with, or shortly prior to, treatment with cis-DDP. No potentiating effect was seen when zilascorb (2H) treatment occurred after removal of cis-DDP. Furthermore, the data showed that the potentiating effect of zilascorb (2H) reached a maximum at concentrations of between 2 and 4 mM. The underlying mechanism for this potentiation is unknown, but could possibly be related to the effect of zilascorb (2H) on protein synthesis. Alternatively, it is also possible that generation of free radicals from the ascorbate moiety of the zilascorb (2H) molecule may increase cellular damage induced by cis-DDP, or inhibit repair or restitution of cis-DDP-induced damage. Also, in cells of a cis-DDP-resistant subline, NHIK 3025/DDP zilascorb (2H) was found to potentiate the effect of cis-DDP. The cis-DDP-resistant cells, however, were found to be partly cross-resistant to cytotoxic treatments with zilascorb (2H).
Integrin α8β1 mediates adhesion to LAP-TGFβ1 (2002)

The development of fibrosis is a common response to a variety of injuries and results in the net accumulation of matrix proteins and impairment of normal organ function. We previously reported that the integrin alpha8beta1 is expressed by alveolar interstitial cells in normal lung and is upregulated during the development of fibrosis. TGFbeta1 is an important mediator of the inflammatory response in pulmonary fibrosis. TGFbeta1 is secreted as a latent protein that is non-covalently associated with latency-associated peptide (LAP) and requires activation to exert its effects. LAP-TGFbeta1 and LAP-TGFbeta3 contain the tripeptide sequence, arginine-glycine-aspartic acid (RGD), a known integrin recognition motif. The integrin alpha8beta1 binds to several ligands such as fibronectin and vitronectin through the RGD sequence. Recent reports demonstrate that the integrins alphavbeta1, alphavbeta6 and alphavbeta8 adhere to LAP-TGFbeta1 through the RGD site. Therefore, we asked whether LAP-TGFbeta1 might be a ligand for alpha8beta1 and whether this may be important in the development of fibrosis. We found that cell lines transfected with alpha8 subunit were able to spread on and adhere to recombinant LAP-TGFbeta1 significantly better than mock transfected cell lines. alpha8-transfected cells were also able to adhere to LAP-TGFbeta3 significantly better than mock transfected cells. Adhesion to LAP-TGFbeta1 was enhanced by activation of alpha8beta1 by Mn(2+), or 8A2, an integrin beta1 activating antibody. Furthermore, cell adhesion was abolished when we used a recombinant LAP-TGFbeta1 protein in which the RGD site was mutated to RGE. alpha8beta1 binding to LAP-TGFbeta1 increased cell proliferation and phosphorylation of FAK and ERK, but did not activate of TGFbeta1. These data strongly suggest that LAP-TGFbeta1 is a ligand of alpha8beta1 and interaction of alpha8beta1 with LAP-TGFbeta1 may influence cell behavior.
Audiometric Threshold Shift Definitions: Simulations and Suggestions (2005)

Choice of an STS definition requires three judgments that cannot be made based on the type of analysis discussed in this report: The range of frequencies to be tested, whether to require that an STS definition be applied twice, and the acceptable magnitude of false-positive error. Once these judgments have been made, the techniques discussed here can assist in selecting the appropriate decision variable (typically PTA or AF) and a criterion value that yields an acceptable false-positive rate. Additional research using the techniques described in this report with either new or old audiometric databases could help determine whether any STS definition is significantly better than the current OSHA definition.
The effects of discontinuing pioglitazone in patients with nonalcoholic steatohepatitis† (2007)

These findings suggest that long-term therapy with pioglitazone may be necessary to maintain improvements in disease activity in patients with NASH, although weight gain during treatment may ultimately limit its beneficial effects.
Substitution of 15-hydroxyeicosatetraenoic acid in the phosphoinositide signaling pathway. (1991)

Consideration of how 15-hydroxyeicosatetraenoic acid (15-HETE) might exert its biological actions led us to investigate the consequences of its incorporation into bovine pulmonary arterial endothelial cell (BPAEC) phospholipids [3H]15(S)-HETE was incorporated mainly (89%) into phosphatidylinositols, predominantly as 1-stearoyl-2-(15-HETE) phosphatidylinositol. By contrast 5(S)- and 12(S)-HETE are incorporated largely into phosphatidylcholine. 15-HETE had a long persistence in the phosphatidylinositols of BPAEC with a half-life of 12 h; its uptake was concentration-dependent, and it accumulated so that 2-(15-HETE) phosphatidylinositol accounted for 10.9% of total phosphatidylinositol after four sequential 1-h incubations of cells with 1 microM 15(S)-HETE. After incubating BPAEC with 15(S)-HETE, stimulation of the cells with bradykinin led to an increase in the levels of 15-HETE. Following addition of bradykinin to cells exposed to [3H]15(S)-HETE, a radiolabeled diacylglycerol was isolated. A mass spectrum of its pentafluorobenzoyl (PFBO) trimethylsilyl (Me3Si) derivative obtained with direct electron capture negative ion chemical ionization mass spectrometry (DNICI/MS) revealed a molecular anion and fragment ions that were identical with those observed with the PFBO/Me3Si derivative of authentic 1-stearoyl-2-(15-HETE) diacylglycerol. There was a lesser quantity of 1-oleoyl-2-(15-HETE) diacylglycerol. An increase in the quantity of 1-stearoyl-2-(15-HETE) diacylglycerol from 6 +/- 1.4 pmol/10(7) cells in the basal state to 12.7 +/- 3.5 after bradykinin was measured by DNICI/MS utilizing a deuterium-labeled analog as an internal standard. Thus, incorporation of 15(S)-HETE into the phosphatidylinositol of these cells led to the release of altered second messengers.
Pharmacokinetics and bioactivity of 1,4,7,10-tetra-azacylododecane off',N'',N'''-tetraacetic acid (DOTA)-bismuth-conjugated anti-Tac antibody for alpha-emitter (212Bi) therapy. (1993)

A major factor that is critical to the potential effectiveness of alpha-emitter 212Bi radioimmunotherapy is the design of radiometal-chelated antibodies that will be stable in vivo. The chelate should bind the radiometal firmly to minimize release of the radionuclide from the monoclonal antibody-chelate complex. The present study examines a member of a new class of polyamine carboxylate chelating compounds, the DOTA ligands, for conjugating radiometal ions to antibody. Biocompatibility and stability are assessed with the anti-Tac monoclonal antibody that is directed against the human interleukin 2 receptors. The scientific basis for the clinical use of this antibody in radioimmunotherapy is that resting normal cells do not express the interleukin 2 receptor, whereas the receptor is expressed on the surface of certain neoplasms and by activated T-cells in select autoimmune diseases and in allograft rejection. First, we examined the impact of the labeling procedure and the presence of the chelate, DOTA, on antibody bioavailability and survival. Next, we studied the capacity of the antibody-chelate complex to retain radiobismuth. Coupling DOTA to antibody or adding Bi(III) to DOTA-coupled antibody did not disturb antibody immunoreactivity in in vitro binding studies. In addition, as analyzed by in vivo studies, DOTA-antibody dummy labeled with nonradioactive bismuth showed pharmacokinetics and tissue distribution identical to those of antibody not modified with DOTA. DOTA-anti-Tac charged with radioactive bismuth showed pharmacokinetics identical to radioiodinated dummy-labeled DOTA-antibody, suggesting little premature release of radioactive bismuth from the antibody complex. Moreover, in the early, therapeutically relevant time points (2 h and 6 h), there was no significant preferential accumulation of bismuth in any organ. At the 5-day time point, beyond the range of therapeutic interest, there was delayed excretion of bismuth from reticuloendothelial tissues relative to radioiodine from catabolized antibody. Excretion of catabolized DOTA-bismuth had an apparent t1/2 of approximately 1 day without the marked renal accumulation typical of the free bismuth ion. The compatibility of DOTA conjugation with antibody bioactivity and the stability of the radioactive bismuth complex in vivo provide important preclinical validation of the potential utility of this new chelating agent for 212Bi monoclonal antibody radioimmunotherapy in humans.
Competing Interactions and Levels of Ordering in Self-Organizing Polymeric Materials (1997)

The sophisticated use of self-organizing materials, which include liquid crystals, block copolymers, hydrogen- and π-bonded complexes, and many natural polymers, may hold the key to developing new structures and devices in many advanced technology industries. Synthetic materials are usually designed with only one structure-forming process in mind. However, combination of both complementary and antagonistic interactions in macromolecular systems can create order in materials over many length scales. Here polymer materials that make use of competing molecular interactions are summarized, and the prospects for the further development of such materials through both synthetic and processing pathways are highlighted.
Prognostic impact of CD68 and kallikrein 6 in human glioma. (2009)

Kallikrein 6 was down-regulated in malignant glioma, but this differential expression did not have an impact on patient prognosis. In contrast, immunostaining of glioma tissue for CD68 and for cathepsin B may be used for prognosis of survival in these patients. This finding suggests that besides the known role of cathepsin B in invasion and angiogenesis, CD68 may be also associated with glioma progression.
Large-scale in vitro expansion of polyclonal human CD4+CD25high regulatory T cells (2004)

CD4(+)CD25+ regulatory T (Treg) cells are pivotal for the maintenance of self-tolerance, and their adoptive transfer gives protection from autoimmune diseases and pathogenic alloresponses after solid organ or bone marrow transplantation in murine model systems. In vitro, human CD4(+)CD25+ Treg cells display phenotypic and functional characteristics similar to those of murine CD4(+)CD25+ Treg cells: namely, hyporesponsiveness to T-cell receptor (TCR) stimulation and suppression of CD25- T cells. Thus far, the detailed characterization and potential clinical application of human CD4(+)CD25+ Treg cells have been hampered by their paucity in peripheral blood and the lack of appropriate expansion protocols. Here we describe the up to 40 000-fold expansion of highly purified human CD4(+)CD25high T cells in vitro through the use of artificial antigen-presenting cells for repeated stimulation via CD3 and CD28 in the presence of high-dose interleukin 2 (IL-2). Expanded CD4(+)CD25high T cells were polyclonal, maintained their phenotype, exceeded the suppressive activity of freshly isolated CD4(+)CD25high T cells, and maintained expression of the lymph node homing receptors L-selectin (CD62L) and CCR7. The ability to rapidly expand human CD4(+)CD25high Treg cells on a large scale will not only facilitate their further exploration but also accelerate their potential clinical application in T cell-mediated diseases and transplantation medicine.