gebhart/patrepeval huggingface dataset:
HTLV-III neutralizing antibody development in transfusion-dependent seropositive patients with beta-thalassemia. (1987)

Sera collected in New York in 1984 from 77 patients with homozygous beta-thalassemia were assayed for antibodies to HTLV-III by ELISA and Western blot techniques. Eight (12%) of the 66 hypertransfused thalassemics were seropositive. Retrospective sera of these eight individuals were examined by radioimmune precipitation (RIP), and assays for neutralization of virus infectivity were performed. With seroconversion, antibodies to viral envelope proteins appeared first and were correlated with development of neutralizing antibody. Affinity purified gp120, the major envelope glycoprotein of HTLV-III, blocked viral infectivity and absorbed neutralizing antibody activity from a positive serum. Neutralizing antibody titers mirrored antibody titers to gp120 by RIP. Antibody to gp120 sometimes occurred in the absence of neutralizing antibody, although the reverse was not true. One thalassemia patient who exhibited antibody to gp120 for 3 yr post-seroconversion failed to develop neutralizing antibody, acquired the acquired immunodeficiency syndrome with central nervous system involvement and lymphoma, and subsequently died. In contrast, all other seropositive thalassemics possessed neutralizing antibodies, and were asymptomatic or exhibited only lymphadenopathy. These results indicate that gp120 elicits neutralizing antibodies in the course of natural infection with HTLV-III. The relationship seen here between neutralizing antibody and better clinical outcome needs to be verified by additional studies.
Combined OX40L and mTOR blockade controls effector T cell activation while preserving T reg reconstitution after transplant (2017)

A critical question facing the field of transplantation is how to control effector T cell (T<sub>eff</sub>) activation while preserving regulatory T cell (T<sub>reg</sub>) function. Standard calcineurin inhibitor-based strategies can partially control T<sub>effs</sub>, but breakthrough activation still occurs, and these agents are antagonistic to T<sub>reg</sub> function. Conversely, mechanistic target of rapamycin (mTOR) inhibition with sirolimus is more T<sub>reg</sub>-compatible but is inadequate to fully control T<sub>eff</sub> activation. In contrast, blockade of OX40L signaling has the capacity to partially control T<sub>eff</sub> activation despite maintaining T<sub>reg</sub> function. We used the nonhuman primate graft-versus-host disease (GVHD) model to probe the efficacy of combinatorial immunomodulation with sirolimus and the OX40L-blocking antibody KY1005. Our results demonstrate significant biologic activity of KY1005 alone (prolonging median GVHD-free survival from 8 to 19.5 days), as well as marked, synergistic control of GVHD with KY1005 + sirolimus (median survival time, >100 days; <i>P</i> < 0.01 compared to all other regimens), which was associated with potent control of both T<sub>H</sub>/T<sub>C</sub>1 (T helper cell 1/cytotoxic T cell 1) and T<sub>H</sub>/T<sub>C</sub>17 activation. Combined administration also maintained T<sub>reg</sub> reconstitution [resulting in an enhanced T<sub>reg</sub>/T<sub>eff</sub> ratio (40% over baseline) in the KY1005/sirolimus cohort compared to a 2.9-fold decrease in the unprophylaxed GVHD cohort]. This unique immunologic signature resulted in transplant recipients that were able to control GVHD for the length of analysis and to down-regulate donor/recipient alloreactivity despite maintaining anti-third-party responses. These data indicate that combined OX40L blockade and sirolimus represents a promising strategy to induce immune balance after transplant and is an important candidate regimen for clinical translation.
Influence of skin depth on NMR coil impedance (1988)

A derivation of the change in electrical impedance of an NMR surface coil produced by inductive coupling with a conducting medium is presented. The effect of skin depth is treated explicitly. Theoretical predictions of coil sample resistance and frequency offset are compared with those observed experimentally in a variety of circular surface coils and sample conductivities.
Knowledge discovery and data mining: towards a unifying framework (1996)

This paper presents a first step towards a unifying framework for Knowledge Discovery in Databases. We describe links between data mining, knowledge discovery, and other related fields. We then define the KDD process and basic data mining algorithms, discuss application issues and conclude with an analysis of challenges facing practitioners in the field. keywords: Knowledge Discovery in Databases (KDD), Data mining, overview article, large databases, automated analysis, issues and challenges in data mining. To appear: Proceedings of the Second International Conference on Knowledge Discovery and Data Mining (KDD-96), Portland, Oregon, August 2-4, 1996, AAAI Press. http://wwwaig. jpl.nasa.gov/kdd96 Knowledge Discovery and Data Mining: Towards a Unifying Framework Usama Fayyad Microsoft Research One Microsoft Way Redmond, WA 98052, USA fayyad@microsoft.com Gregory Piatetsky-Shapiro GTE Laboratories, MS 44 Waltham, MA 02154, USA gps@gte.com Padhraic Smyth Information and Computer S...
Obfuscation as Intellectual Rights Protection in VHDL Language (2007)

Software is more and more frequently distributed inform of source code. Unprotected code is easy to alter and build in others projects. The answer for attacks against intellectual rights is obfuscation, a process that makes software unintelligible but still functional. In this paper we review several generic techniques of obfuscation VHDL (Very High Speed Integrated Circuit Hardware Description Language) code and present a set of them for software protection. We are going to describe some related experimental work.
cDNA Cloning and Sequence Analysis of βig-h3, a Novel Gene Induced in a Human Adenocarcinoma Cell Line after Treatment with Transforming Growth Factor-β (1992)

Transforming growth factor-beta (TGF-beta) is capable of affecting the proliferation of many cell types. To identify novel genes whose protein products may mediate cellular responses to this factor, a cDNA library was made from mRNA isolated from a human lung adenocarcinoma cell line (A549) that had been treated for 3 days with TGF-beta. The library was screened by differential hybridization and a cDNA clone, beta ig-h3, was isolated. This gene was induced up to 20-fold in A549 cells after 2 days of treatment with TGF-beta 1. It was also induced in several other cell lines, including PC-3 and H2981. DNA sequence analysis of beta ig-h3 indicated that it encoded a novel protein, beta IG-H3, of 683 amino acids, which contained an amino-terminal secretory sequence and a carboxy-terminal Arg-Gly-Asp (RGD) sequence that can serve as a ligand recognition site for several integrins. beta IG-H3 also contained short amino acid regions homologous to similar regions in Drosophila fasciclin-I and four homologous internal domains, which can be folded into a potential bivalent structure and could act as a bridge between cells expressing the appropriate ligand. beta ig-h3 RNA was detected in several cell lines and tissues. COS cells transfected with plasmids encoding beta IG-H3 secreted a major 68-kD protein that was detected by immunoblotting using antipeptide antibodies. Since beta ig-h3 is induced in several cell lines whose proliferation is affected by TGF-beta 1, it may be involved in mediating some of the signals of this multifunctional growth modulator.
Identification of a Novel Immunoreceptor Tyrosine-based Activation Motif-containing Molecule, STAM2, by Mass Spectrometry and Its Involvement in Growth Factor and Cytokine Receptor Signaling Pathways (2000)

In an effort to clone novel tyrosine-phosphorylated substrates of the epidermal growth factor receptor, we have initiated an approach coupling affinity purification using anti-phosphotyrosine antibodies to mass spectrometry-based identification. Here, we report the identification of a signaling molecule containing a Src homology 3 domain as well as an immunoreceptor tyrosine-based activation motif (ITAM). This molecule is 55% identical to a previously isolated molecule designated signal transducing adaptor molecule (STAM) that was identified as an interleukin (IL)-2-induced phosphoprotein and is therefore designated STAM2. Tyrosine phosphorylation of STAM2 is induced by growth factors such as epidermal growth factor and platelet-derived growth factor as well as by cytokines like IL-3. Several of the deletion mutants tested except the one containing only the amino-terminal region underwent tyrosine phosphorylation upon growth factor stimulation, implying that STAM2 is phosphorylated on several tyrosine residues. STAM2 is downstream of the Jak family of kinases since coexpression of STAM2 with Jak1 or Jak2 but not an unrelated Tec family kinase, Etk, resulted in its tyrosine phosphorylation. In contrast to epidermal growth factor receptor-induced phosphorylation, this required the ITAM domain since mutants lacking this region did not undergo tyrosine phosphorylation. Finally, overexpression of wild type STAM2 led to an increase in IL-2-mediated induction of c-Myc promoter activation indicating that it potentiates cytokine receptor signaling.
Survey of naturally occurring CD4 + T cell responses against NY-ESO-1 in cancer patients: Correlation with antibody responses (2003)

NY-ESO-1 is one of the most immunogenic proteins described in human cancers, based on its capacity to elicit simultaneous antibody and CD8+ T cell responses in vivo. Although HLA class II restricted epitopes from NY-ESO-1 have been identified, no broad survey has yet established the status of natural CD4+ T cell responses in cancer patients in relation to CD8+ and antibody responses. We used a recently developed general strategy for monitoring CD4+ responses that overcomes the need for prior knowledge of epitope or HLA restriction to analyze a series of 31 cancer patients and healthy donors for the presence of CD4+ T cells to NY-ESO-1, and related this response to NY-ESO-1 expression in tumor cells and serum antibodies to NY-ESO-1. None of the 18 patients that tested seronegative for NY-ESO-1 had detectable CD4+ T cell responses. On the contrary, 11 of 13 cancer patients with serum antibodies to NY-ESO-1 had polyclonal CD4+ T cell responses directed against various known and previously undescribed NY-ESO-1 epitopes. NY-ESO-1 peptide 80-109 was the most immunogenic, with 10 of 11 patients responding to this peptide. We show here that 12-mer determinants from NY-ESO-1 eliciting a CD4+ T cell response were peptide 87-98 with promiscuous HLA class II presentation, peptide 108-119 restricted by HLA-DP4, and peptides 121-132 and 145-156, both shorter epitopes from previously described HLA-DR4 peptides, also presented by HLA-DR7. This study represents the next step in compiling a comprehensive picture of the adaptive immune response to NY-ESO-1, and provides a general strategy for analyzing the CD4+ T cell response to other tumor antigens eliciting a humoral immune response.
Characterization of Actin and Poly-L-proline Binding Sites of Profilin with Monoclonal Antibodies and by Mutagenesis (1996)

We characterized several deletion and substitution mutations of Acanthamoeba profilin and nine monoclonal antibodies to Acanthamoeba profilin. The results provide two independent lines of evidence about the binding sites for actin and poly-L-proline on the profilin molecule. This new evidence is consistent with the main conclusions about these binding sites from previous structural and mutagenic studies. Mutagenesis also revealed that the native structure of profilin is very sensitive to substitutions and deletions at the C terminus. For example, profilin with a deletion of the eight C-terminal residues has many of the physical properties of a molten globule, yet remarkably still binds to actin. This instability may account for the lack of function of similar mutants in yeast.
Negative regulation of the P o gene in Schwann cells: suppression of Po mRNA and protein induction in cultured Schwann cells by FGF2 and TGFβ1, TGFβ2 and TGFβ3 (1994)

During the development of peripheral nerves, Schwann cells are induced to form myelin sheaths round the larger axons. This process involves a complex series of events and the nature of the molecular signals that regulate and control myelin formation in Schwann cells is not well understood. Our previous experiments on rat Schwann cells in vitro, using serum-free defined medium, showed that a myelin-related protein phenotype could be induced in early postnatal Schwann cells in culture by elevation of intracellular cyclic AMP levels in the absence of growth factors, conditions under which the cells are not dividing. Cells with this phenotype expressed the major myelin glycoprotein P0 and expression of p75 NGF receptor, N-CAM, GFAP and A5E3 proteins was down-regulated. These changes are all characteristics associated with myelination in vivo. In contrast, when cyclic AMP levels were elevated in the presence of serum, suppression of cyclic AMP-induced differentiation resulted and DNA synthesis was induced. In this paper, we have used this model system and extended our analysis to explore the relationship between defined growth factors and suppression of myelination. We have used pure recombinant growth factors normally present in peripheral nerves, i.e. FGF1 and FGF2 and TGF beta 1, TGF beta 2, and TGF beta 3 and shown that, like serum, they can strongly suppress the forskolin-mediated induction of the P0 gene, both at the level of mRNA and protein synthesis. For both growth factor families, the suppression of P0 gene expression is dose-dependent and takes place in serum-starved cells that are mitotically quiescent. In the case of FGF2, however, even more complete suppression is obtained when the cells are simultaneously allowed to enter the cell cycle by inclusion of high concentrations of insulin in the culture medium. The present results raise the possibility that, in addition to the positive axonal signals that are usually envisaged to control the onset of myelination, growth factors present in the nerve may exert negative regulatory signals during development and thus help control the time of onset and the rate of myelination in peripheral nerves.
Determinants of branching tubulogenesis (1995)

Renal Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
Pharmacokinetic drug evaluation of pazopanib for the treatment of uterine leiomyosarcomas (2017)

Uterine leiomyosarcomas (ULMS) represent 1.3% of all uterine malignant tumors. Surgery is the curative treatment for patients with early stage disease. In case of advanced, persistent or recurrent tumor, chemotherapy represents the standard of care, but these patients have a poor prognosis. As the results with available therapies are far from being satisfactory, research is focusing on identification of new compounds. In 2012 the Food and Drug Administration (FDA) licensed pazopanib for the treatment of advanced soft-tissue sarcomas failing previous chemotherapy. Areas covered: The aim of this article is to review the literature on the pharmacokinetics, pharmacodynamics, clinical efficacy and safety of the tyrosine kinase inhibitor (TKI), pazopanib in the treatment of ULMS. Expert opinion: The discovery of some relevant signalling pathways in LMS cells led to the development of new targeted drugs with promising results in the management of these tumors. Pazopanib is a multi-target second-generation TKI with activity against growth factors involved in angiogenesis. It has shown promising results both in terms of efficacy and safety, as shown in the EORTC 62043 Study and the PALETTE trial. Further studies are awaited to evaluate its efficacy in uterine leiomyosarcomas.
Presentation of Exogenous Antigen with Class I Major Histocompatibility Complex Molecules (1990)

Soluble antigens (Ags) in the extracellular fluids are excluded from the class I major histocompatibility complex (MHC)-restricted pathway of Ag presentation in most cells. However, an exogenous Ag can be internalized, processed, and presented in association with class I MHC molecules on specialized Ag-presenting cells (APCs). These APCs express class II molecules and can simultaneously present exogenous Ags to both class I and class II MHC-restricted T cells. These APCs may be important participants in the regulation of host immune responses. This APC activity may explain several phenomena of cytotoxic T lymphocyte (CTL) priming in vivo and might be exploited for eliciting CTL responses to protein vaccines.
Direct dideoxy sequencing of genomic DNA by ligation-mediated PCR (1994)

A confocal image of pachytene staged maize meiotic chromosomes hybridized with a probe for knob heterochromatin.The knob probe is detected by fluorescein-conjugated antibodies, and the chromosomes are counterstained with propidium iodide as described
Enhanced expression of GM2/GD2 synthase mRNA in human gastrointestinal cancer (1995)

These results suggest that expression of the beta-1,4GalNAcT gene is a key step in the molecular mechanisms underlying the regulation of cancer-associated GM2 expression in the stomach and the colon.
Selective Deposition of Metal Nanoparticles Inside or Outside Multiwalled Carbon Nanotubes (2009)

A general method is described for the deposition of metal nanoparticles selectively either inside or outside of carbon nanotubes (CNTs). The method is based on the difference in the interface energies of organic and aqueous solutions with the CNT surface. Because of their lipophilic character, the organic solvent better wets the surface of the nanotubes compared to water and penetrates into the inner volume. The precise control of the volume of each phase allows filling the CNT with the organic phase and covering its outer surface with the aqueous one. Hence, metal nanoparticles can be put with high selectivity either inside or outside the CNT, just by choosing in which solvent the metal precursor is dissolved. SEM, TEM, and 3D-TEM investigations show that a selectivity in localization close to 75% can be reached by this technique. The nanoparticles are homogeneously dispersed and present a narrow size distribution, centered on 5 nm. In this way, one can decorate either the inner or the outer surface of open CNTs, without the need of discriminating the diameter of the opening and without any further step of functionalization than a treatment with nitric acid.
Experiments in Refilling the Lens (1964)

The ancient procedure of cataract couching has, in more recent times, been superseded by removal of the lens. Most recently prosthetic lenses have been implanted into the aphakic eye, and there has been talk of transplantation of the lens and even of regrowth of the lens in man. Theoretically the best replacement of the lens, short of its regrowth, would be evacuation of the lens contents and replacement by a suitably transparent substance. The purpose of the present paper is to report such an attempt. The lens substance is evacuated through a small opening in the capsule and replaced with transparent material. The new lens is thus held in its normal position and retains its normal connections. With an elastic or viscid filler it might even be possible to preserve accommodation. Beef lenses have been evacuated and refilled in vitro by the following means. The lens capsule is punctured by
T-Antigen in normal and neoplastic urothelium (1986)

The expression of the Thomsen-Friedenreich antigen (T-antigen) in normal and neoplastic urothelium was investigated using paraffin-processed and fresh frozen tissue sections obtained by biopsy from 56 patients. The T-antigen was detected through its binding to the peanut agglutinin (PNA) with two methods: a biotin-avidin-peroxidase system or a modified red cell adherence test. In vitro treatment of the tissue sections with neuraminidase induced PNA binding in the normal and neoplastic urothelium as well as the red blood cells and the vascular endothelium. Spontaneous PNA binding was absent in normal bladder epithelium, but was observed in 10% of the noninvasive and 65% of the invasive transitional cell carcinomas (TCC). The positive reactions were seen in the cytoplasm, cell surface, and mucin. These results were correlated with the light and electron microscopic findings and with the detectability of the A, B, H blood group antigens in the same tissues. Ultrastructurally, the PNA binding sites frequently corresponded to the Golgi apparatus and to secretory products which stained with Alcian blue. About 90% of TCCs with spontaneous PNA binding did not express the expected blood group antigen. The latter was also undetectable in 54% of TCCs lacking spontaneous PNA binding. It appears, therefore, that the expression of T-antigen occurs later in the evolution of aggressive TCCs, usually when they have advanced to invasive stages. The finding of spontaneous T-antigen unmasking correlates with the presence of invasion and a higher risk for metastatic involvement of regional lymph nodes.
Tissue Engineering of Flexor Tendons: Optimization of Tenocyte Proliferation Using Growth Factor Supplementation (2006)

A significant problem in flexor tendon repair is the lack of suitable graft material for reconstruction. The ex vivo production of flexor tendon graft constructs requires the expansion of primary cells. Growth factors, such as platelet-derived growth factor-BB (PDGF-BB), insulin-like growth factor-1 (IGF-1), and basic fibroblast growth factor (bFGF), are known to promote tendon healing and tendon cell proliferation. The purpose of these experiments was to optimize tenocyte proliferation in 3 tendon cell populations using growth factor supplementation. Cells of the synovial sheath, epitenon, and endotenon were isolated from rabbit flexor digitorum profundus tendons and maintained in culture. Cell cultures were supplemented with IGF-1, PDGF-BB, and bFGF alone and in combination. The conditions used for individual growth factor supplementation were IGF-1 (10, 50, and 100 ng/mL), PDGF-BB (1, 10, and 50 ng/mL), and bFGF (0.5, 1, and 5 ng/mL). The conditions used for combinations of growth factors were IGF-1 + PDGF-BB (50 + 10 and 100 + 50 ng/mL, respectively) and IGF-1 + PDGF-BB+ bFGF (50 + 10 + 1; 50 + 10 + 5; 100 + 50 + 1; and 100 + 50 + 5 ng/mL, respectively). For all 3 tendon cell populations, proliferation at 72 h was greater in the presence of individual growth factors as compared to controls. With PDGF-BB (50 ng/mL) supplementation, mean absorbance values increased 97% (0.57 to 1.13) in S cells, 37% (0.51 to 0.70) in E cells, and 33% (0.33 to 0.44) in T cells ( p < 0.001). In addition, a synergistic effect was observed. The combination of growth factors resulted in greater proliferation as compared to maximal doses of individual growth factors. In cultures supplemented with IGF-1 (100 ng/mL) +PDGF-BB (50 ng/mL), mean absorbance increased 114% (0.57 to 1.22) in S cells, 63% (0.51 to 0.831) in E cells, and 47% (0.33 to 0.48) in T cells ( p < 0.001). IGF-1 (100 ng/mL) + PDGF-BB (50 ng/mL) + bFGF (5 ng/mL) resulted in the greatest amount of cell proliferation for all 3 tendon cell populations. The mean absorbances increased 251% in S cells, 98% in E cells, and 106% in T cells ( p < 0.001). In summary, IGF-1, PDGF-BB, and bFGF can be used in combination to maximize tenocyte proliferation. Synergism among growth factors may provide a means to facilitate tendon engineering.