gebhart/patrepeval huggingface dataset:
Identification of a novel subunit of the type I interferon receptor localized to human chromosome 21 (1993)

Expression in mouse cells of the cloned human IFN alpha receptor (IFN alpha R) subunit selectively confers response and binding to human IFN alpha 8, indicating that other subunits are involved in IFN alpha binding. We report here that a new monoclonal antibody (mAb), termed IFNaR beta 1, recognizes a novel IFN alpha R subunit different from the one recently cloned and distinct from the alpha subunit recognized by the IFN alpha R3 mAb. The IFNaR beta 1 mAb blocks the biological effect of seven different Type I IFNs. Immunoprecipitations after cell surface iodination demonstrate that the IFNaR beta 1 mAb recognizes a protein with a molecular mass of 100 kDa in Daudi and U-266 cells that express normal IFN alpha R. However, a 55-kDa protein instead of the 100-kDa product was immunoprecipitated in the IFN alpha-resistant U-937 cell line that express the variant form of the receptor. We also demonstrate that the gene that codes for this novel IFN alpha R subunit maps to human chromosome 21, as do the cloned IFN alpha R subunit and the alpha subunit, indicating the existence of a locus on this chromosome that regulates binding for Type I IFNs.
Development of progressive kidney damage and myeloma kidney in interleukin-6 transgenic mice (1994)

Interleukin-6 (IL-6) is a pleiotropic cytokine that has been postulated as playing a role in the pathogenesis of multiple myeloma, chronic autoimmune diseases, and alcoholic liver cirrhosis. We generated transgenic mice carrying a fusion between the mouse metallothionein-I (MT-I) gene promoter and the human IL-6 cDNA. MT-I/IL-6 transgenics express IL-6 constitutively in the liver and secrete the cytokine in the blood. They show initially activation of acute-phase response genes and accumulation of alpha 2- and beta-globulins in the plasma, which is followed by polyclonal hypergammaglobulinemia. MT-I/IL-6 transgenics die between 12 to 20 weeks of age. Histologic examination of transgenic animals at different ages and after necropsy showed, as expected from previous studies of IL-6 disregulation in vivo, an increase in the number of megakaryocytes in the spleen and bone marrow and, at later stages, IgG plasmacytosis in the spleen, lymph nodes, and thymus. However, no plasma cell infiltration was detected in other organs. The distinguishing feature of MT-I/IL-6 transgenics is the development of a progressive kidney pathology, in which the initial membranous glomerulonephritis is followed by focal glomerulosclerosis and finally by extensive tubular damage that reproduces the damage observed in patients at terminal stages of multiple myeloma (myeloma kidney). The pathogenetic role of IL-6 overproduction and of the resulting serum protein overload in the kidney damage is discussed.
NMR Characterization of Lanthanide(3+) Complexes of Tetraazatetrakisphosphinato and Tetraazatetrakisphosphonato Ligands (2009)

Abstract The three‐dimensional structures in aqueous solution of the entire series of the Ln 3+ complexes [Ln(DOTP*‐Et)] − (formed from the free ligand P , P′ , P″ , P′′′ ‐[1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetrayltetrakis(methylene)]tetrakis[ P ‐ethylphosphinic acid] (H 4 DOTP*‐Et) were studied by NMR techniques to rationalize the parameters governing the relaxivity of the Gd 3+ complex and evaluate its potential as MRI contrast agent. From the 1 H‐ and 31 P‐NMR lanthanide‐induced‐shift (LIS) values, especially of the [Yb(DOTP*‐Et)] − complex, it was concluded that the [Ln(DOTP*‐Et)] − complexes adopt in solution twisted square antiprismatic coordination geometries which change gradually their coordination‐cage structure along the lanthanide series. These complexes have no inner‐sphere‐H 2 O coordination, and preferentially have the ( R , R , R , R ) configuration of the P‐atoms in the pendant arms. Self‐association was observed in aqueous solution for the tetraazatetrakisphosphonic acid ester complexes [Ln(DOTP*‐OEt)] − (=[Ln(DOTP‐Et)] − ) and [Ln(DOTP*‐OBu)] − (=[Ln(DOTP‐Bu)] − ) at and above 5 m M concentration, through analysis of 31 P‐NMR, EPR, vapor‐pressure‐osmometry, and luminescence‐spectroscopic data. The presence of the cationic detergent cetylpyridinium chloride (CPC; but not of neutral surfactants) shifts the isomer equilibrium of [Eu(DOTP*‐OBu)] − to the ( S , S , S , S ) form which selectively binds to the cationic micelle surface.
Centrifuge-Based Fluidic Platforms (2004)

In this paper, centrifuge-based microfluidic platforms are reviewed and compared with other popular microfluidic propulsion methods. The underlying physical principles of centrifugal pumping in microfluidic systems are presented and the various centrifuge fluidic functions such as valving, decanting, calibration, mixing, metering, heating, sample splitting, and separation are introduced. Those fluidic functions have been combined with analytical measurement techniques such as optical imaging, absorbance and fluorescence spectroscopy and mass spectrometry to make the centrifugal platform a powerful solution for medical and clinical diagnostics and high-throughput screening (HTS) in drug discovery. Applications of a compact disk (CD)-based centrifuge platform analyzed in this paper include two-point calibration of an optode-based ion sensor, an automated immunoassay platform, multiple parallel screening assays, and cellular-based assays. The use of modified commercial CD drives for high-resolution optical imaging is discussed as well. From a broader perspective, we compare technical barriers involved in applying microfluidics for sensing and diagnostics as opposed to applying such techniques to HTS. The latter poses fewer challenges and explains why HTS products based on a CD fluidic platform are already commercially available, while we might have to wait longer to see commercial CD-based diagnostics.
Sonic hedgehog is involved in osteoblast differentiation by cooperating with BMP‐2 (2002)

The roles of Sonic hedgehog (Shh) and Bone morphogenetic protein-2 (Bmp-2) in osteoblast differentiation were investigated using in vitro cell systems. Recombinant amino-terminal portion of SHH (rSHH-N) dose dependently stimulated ALP activity in C3H10T1/2 and MC3T3-E1 cells. rSHH-N induced expression of Osteocalcin mRNA in C3H10T1/2 cells. A soluble form of the receptor for type IA BMP receptor antagonized rSHH-N-induced ALP activity in C3H10T1/2 and MC3T3-E1 cells, indicating that BMPs are involved in SHH-induced osteoblast differentiation. Simultaneous supplement with rSHH-N and BMP-2 synergistically induced ALP activity and expression of Osteocalcin mRNA in C3H10T1/2 cells. Pretreatment with rSHH-N for 6 h enhanced the response to BMP-2 by increasing ALP activity in C3H10T1/2 and MC3T3-E1 cells. Stimulatory effects of rSHH-N and additive effects with rSHH-N and BMP-2 on ALP activity were also observed in mouse primary osteoblastic cells. Transplantation of BMP-2 (1 microg) into muscle of mice induced formation of ectopic bone, whereas transplantation of r-SHH-N (1-5 microg) failed to generate it. These results indicate that Shh plays important roles in osteoblast differentiation by cooperating with BMP.
Inelastic Electron Tunneling Spectroscopy (1983)

Inelastic electron tunneling spectroscopy is a useful technique for the study of vibrational modes of molecules adsorbed on the surface of oxide layers in a metal-insulator-metal tunnel junction. The technique involves studying the effects of adsorbed molecules on the tunneling spectrum of such junctions. The data give useful information about the structure, bonding, and orientation of adsorbed molecules. One of the major advantages of inelastic electron tunneling spectroscopy is its sensitivity. It is capable of detecting on the order of 10(10) molecules (a fraction of a monolayer) on a 1-square-millimeter junction. It has been successfully used in studies of catalysis, biology, trace impurity detection, and electronic excitations. Because of its high sensitivity, this technique shows great promise in the area of solid-state electronic chemical sensing.
Hybrid III-V/Silicon laser based on DVS-BCB bonding (2008)

Recent years have witnessed an increasing research interest in hybrid lasers based on evanescent coupling between III-V materials and silicon waveguides. Recently reported state-of-the-art devices utilize molecular die-to-wafer bonding of III-V epitaxial layers to silicon waveguides, which imposes strict requirements on the cleanliness and quality of the bonded surfaces. In this paper, we propose a hybrid III-V/silicon laser based on adhesive DVS-BCB bonding providing less strict surface quality requirements and a fabrication procedure suitable for large-scale production. The general layout of the device and its simulated properties are presented and discussed.
Clinical and Immunologic Evaluation of NeuraminidaseSpecific Influenza A Virus Vaccine in Humans (1977)

Groups of schoolchildren were immunized with an inactivated recombinant influenza virus vaccine specific for the neuraminidase antigen of Port Chalmers influenza A virus (Heq1N2Ch), a conventional biphasic Port Chalmers strain of influenza virus vaccine (H3ChN2Ch), or a placebo. Immunization with either virus vaccine was found to be safe and had no major adverse effects. Immunization with the Heq1N2Ch vaccine resulted in no specific hemagglutination-inhibiting antibody response to H3Ch antigen, although a specific neuraminidase antibody response to N2Ch antigen was observed in greater than 90% of the vaccinees. A subsequent natural outbreak of influenza virus resulted in serologically proven infection with H3Ch virus in 26% of vaccinees receiving H3ChN2Ch virus vaccine, 47% of those receiving Heq1N2Ch virus vaccine, and 44% of those receiving a placebo. However, the protective efficacy against illness was 74.3% for the H3ChN2Ch vaccine and only 51.4% for the Heq1N2Ch vaccine. Regardless of the type of vaccine employed, vaccinees with serologic evidence of infection and clinical illness were found to have very low titers of hemagglutination-inhibiting and neuraminidase antibody. However, vaccinees with serologically proved infection but without clinical illness were found to have titers of antibody to neuraminidase before infection that were four- to eightfold higher than titers in vaccinees who were infected and who had clinical illness.
Block-level 3-D Global Routing With an Application to 3-D Packaging (2006)

Three-dimensional (3-D) packaging via system-on-a-package (SOP) has been recently proposed as an alternative solution to overcome the limitation of system-on-a-chip (SOC) and meet the rigorous requirements of today's mixed signal system integration. The true potential of SOP technology lies in its capability to integrate both active and passive components into a single high speed/density 3-D packaging substrate. The routing environment for 3-D SOP is more advanced than that of the conventional printed circuit board (PCB) or multichip module (MCM) technology - pins are located at all layers of the SOP packaging substrate rather than the topmost layer only, and various types of vias are available for layer-to-layer connections. The contribution of this work is to provide: 1) the formulation of the new block-level 3-D global routing problem under wire length, layer, crosstalk, and congestion minimization and 2) the first global router for 3-D SOP named 3PGR. This paper reviews various approaches for MCM routing algorithms and investigates their applicability to the SOP model. The related experimental results demonstrate the effectiveness of the algorithms
Glucocorticoid‐dextran conjugates as potential prodrugs for colonspecific delivery: Steady‐state pharmacokinetics in the rat (1994)

Chronic colitis, e.g., ulcerative colitis and Crohn's disease, is presently treated with glucocorticoids and other antiinflammatory agents. Side-effects limit chronic glucocorticoid therapy. The dose, and consequently the side-effects, may be reduced by using prodrugs that selectively deliver drug to the colon. We previously synthesized glucocorticoid-dextran conjugates in which dexamethasone was attached to dextran (weight-average molecular weight = 72,600) using dicarboxylic acid linkers (succinate and glutarate). In the present study, dexamethasone-succinate-dextran and dexamethasone-glutarate-dextran were administered to two groups of male Sprague-Dawley rats by intragastric infusion. In two additional groups, disodium dexamethasone phosphate and dexamethasone hemisuccinate were each administered by subcutaneous infusion. In a fifth group, dexamethasone was administered by intragastric infusion. All groups were infused for sufficient time for steady state to be achieved. Colon-specific delivery was quantified using a drug-delivery index (DDI) in which steady-state dexamethasone concentrations in the cecum and colon were compared with those measured in blood after separate administrations of dexamethasone and dexamethasone-dextran conjugate. The colonic DDI values for dexamethasone-succinate-dextran and dexamethasone-glutarate-dextran were approximately seven and four, respectively. These values were a result of higher tissue concentrations and lower blood concentrations of dexamethasone after intragastric administration of the conjugates compared to subcutaneous and intragastric administration of dexamethasone. The pharmacokinetics of methyl-prednisolone was also investigated after subcutaneous infusion. Observed cecal and colonic tissue-to-blood ratios of 19:1 and 12:1, respectively, showed that this drug is extensively delivered to the large intestine even after subcutaneous administration.
Histone Deacetylase Inhibitors in Cancer Therapy (2009)

HDAC inhibitors are an important emerging therapy with single-agent activity against multiple cancers, and have significant potential in combination use.
Werner deconvolution of profile potential field data (1983)

Abstract Werner (1953), in analyzing the magnetic fields of dipping, magnetized dikes, proposed a method of separating the field contributed by a particular dike under study from the interference of neighboring dikes. In addition to being a means of effecting a regional-residual separation, Werner's method of analysis also had the advantage of being easily programmed on a digital computer. This made it a convenient method for analyzing the large amounts of data from reconnaissance aeromagnetic surveys, and it became the basis of the automatic interpretation schemes of Hartmann et al (1971) and Jain (1976). The purpose of this note is to discuss some limitations of the Werner method of deconvolution and also to point out some possible extensions of the method to the general interpretation of potential field data.
Retrovirus-mediated gene therapy for hepatocellular carcinoma: selective and enhanced suicide gene expression regulated by human alpha-fetoprotein enhancer directly linked to its promoter. (1999)

We have previously reported that a retrovirus vector (LNAF0.3TK) carrying a herpes simplex virus thymidine kinase gene regulated only by the 0.3-kb human alpha-fetoprotein (AFP) promoter provides ganciclovir (GCV)-mediated cytotoxicity in high AFP-producing human hepatoma cells but not in low AFP-producing cells. In the present study, a retrovirus vector (LNAF0.3(E+)TK), in which herpes simplex virus thymidine kinase gene expression is under the control of a human AFP enhancer directly linked to its promoter, was constructed and compared with LNAF0.3(E+)TK. In the intermediate and low AFP-producing human hepatoma cells PLC/PRF/5 and huH1/cl.2, respectively, as well as in the high AFP-producing human hepatoma cells (HepG2), LNAF0.3(E+)TK sensitized these cells to GCV in vitro but did not affect cell growth in nonhepatoma cells (HeLa). In an animal model using athymic mice harboring PLC/PRF/5 cells, GCV treatment resulted in more pronounced growth inhibition in the LNAF0.3(E+)TK virus-infected cells than in the LNAF0.3(E+)TK virus-infected cells. These results indicate that the human AFP enhancer that is directly linked to its promoter involves selective and enhanced tumoricidal activity in gene therapy for hepatocellular carcinoma.
Deep-Learning Convolutional Neural Networks Accurately Classify Genetic Mutations in Gliomas (2018)

Our results indicate that for The Cancer Imaging Archives dataset, machine-learning approaches allow classification of individual genetic mutations of both low- and high-grade gliomas. We show that relevant MR imaging features acquired from an added dimensionality-reduction technique demonstrate that neural networks are capable of learning key imaging components without prior feature selection or human-directed training.
Bax Channel Inhibitors Prevent Mitochondrion-mediated Apoptosis and Protect Neurons in a Model of Global Brain Ischemia (2005)

Ischemic injuries are associated with several pathological conditions, including stroke and myocardial infarction. Several studies have indicated extensive apoptotic cell death in the infarcted area as well as in the penumbra region of the infarcted tissue. Studies with transgenic animals suggest that the mitochondrion-mediated apoptosis pathway is involved in ischemia-related cell death. This pathway is triggered by activation of pro-apoptotic Bcl-2 family members such as Bax. Here, we have identified and synthesized two low molecular weight compounds that block Bax channel activity. The Bax channel inhibitors prevented cytochrome c release from mitochondria, inhibited the decrease in the mitochondrial membrane potential, and protected cells against apoptosis. The Bax channel inhibitors did not affect the conformational activation of Bax or its translocation and insertion into the mitochondrial membrane in cells undergoing apoptosis. Furthermore, the compounds protected neurons in an animal model of global brain ischemia. The protective effect in the animal model correlated with decreased cytochrome c release in the infarcted area. This is the first demonstration that Bax channel activity is required in apoptosis.
A Redesigned Vancomycin Engineered for Dual d -Ala- d -Ala and d -Ala- d -Lac Binding Exhibits Potent Antimicrobial Activity Against Vancomycin-Resistant Bacteria (2011)

The emergence of bacteria resistant to vancomycin, often the antibiotic of last resort, poses a major health problem. Vancomycin-resistant bacteria sense a glycopeptide antibiotic challenge and remodel their cell wall precursor peptidoglycan terminus from d-Ala-d-Ala to d-Ala-d-Lac, reducing the binding of vancomycin to its target 1000-fold and accounting for the loss in antimicrobial activity. Here, we report [Ψ[C(═NH)NH]Tpg(4)]vancomycin aglycon designed to exhibit the dual binding to d-Ala-d-Ala and d-Ala-d-Lac needed to reinstate activity against vancomycin-resistant bacteria. Its binding to a model d-Ala-d-Ala ligand was found to be only 2-fold less than vancomycin aglycon and this affinity was maintained with a model d-Ala-d-Lac ligand, representing a 600-fold increase relative to vancomycin aglycon. Accurately reflecting these binding characteristics, it exhibits potent antimicrobial activity against vancomycin-resistant bacteria (MIC = 0.31 μg/mL, VanA VRE). Thus, a complementary single atom exchange in the vancomycin core structure (O → NH) to counter the single atom exchange in the cell wall precursors of resistant bacteria (NH → O) reinstates potent antimicrobial activity and charts a rational path forward for the development of antibiotics for the treatment of vancomycin-resistant bacterial infections.
Interpreting the History of Bloodletting (1995)

Journal Article Interpreting the History of Bloodletting Get access SHIGEHISA KURIYAMA SHIGEHISA KURIYAMA Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of the History of Medicine and Allied Sciences, Volume 50, Issue 1, January 1995, Pages 11–46, https://doi.org/10.1093/jhmas/50.1.11 Published: 01 January 1995
New tandem repeat region in the non-transcribed spacer of human ribosomal RNA gene (1989)

A new repetitive DNA region was identified in the non-transcribed spacer of human rDNA, namely a long (4.6 kb) sequence motif (Xbal element) was present in two copies. The repeating unit composed of two parts. One of them consisted of unique nucleotide sequences, interrupted by some simple sequences. The other, about 3.1 kb long one assembled only from highly repeated simple sequences. The unique sequence region contained two, inverted copies of the human AluI type repetitive DNA family. The authors suggest that the XbaI elements may flank the tandem arrays of human rRNA genes as terminal repeats and they might function both as the origin of rDNA replication and/or site of homologous recombination.
Back to the Future: COX-2 Inhibitors for Chemoprevention and Cancer Therapy (2007)

For more than a century, inhibition of prostaglandin biosynthesis via inhibition of the fatty acid cyclooxygenase (COX) has been achieved by non-steroidal anti-inflammatory drugs (NSAIDs), which targets both COX-1 and COX-2 and as such could be responsible for causing gastrointestinal (GI) toxicity. COX-2 is an inducible enzyme produced by many cell types in response to multiple stimuli. Recently, COX-2 over-expression has been found in several types of human cancers such as colon, breast, prostate and pancreas and appears to control many cellular processes. Because of its role in carcinogenesis, apoptosis, and angiogenesis, it is an excellent target for developing new drugs with selectivity for prevention and/or treatment of human cancers. Development of selective COX-2 inhibitors has been successfully documented and as such showed less toxicity to GI tract as compared to conventional NSAIDs. However, the long term use of COX-2 selective inhibitors showed cardiovascular toxicity, and thus their utilization for cancer prevention and therapy is currently questionable, suggesting that further development of novel COX-2 selective agents are needed. Among many solid tumors, pancreatic cancer has the worst prognosis, and inflammation has been identified as a significant factor in the development of pancreatic malignancy. Several cytokines, reactive oxygen species (ROS) and mediators of inflammatory pathway such as activation of nuclear factor-kappaB (NF-kappaB) and COX-2 leads to an increase in cell proliferation, survival, and inhibition of pro-apoptotic pathway, ultimately resulting in tumor angiogenesis, invasion and metastasis. In this brief review, we summarize the role of COX-2 and discuss some of the experimental data linking inflammation with the development of pancreatic cancer. In addition, we provide further evidence regarding the state of our knowledge toward the development of novel COX-2 targeting agents for the prevention and/or treatment of human cancers especially pancreatic cancer.