gebhart/patrepeval huggingface dataset:
Angiogenic factors in normal endometrium and endometrial adenocarcinoma (2007)

In the endometrium, angiogenesis plays important roles not only in tumor growth but also in the menstrual cycle. The purpose of the present paper was to investigate immunohistochemically the correlation between angiogenic factor expression and angiogenic score in normal and neoplastic endometrium. Immunohistochemical staining for vascular endothelial growth factor (VEGF), angiopoietin (Ang)-1, Ang2, Tie2, CD34 and CD105 was performed on formalin-fixed and paraffin-embedded tissues from 31 normal endometrium and 85 endometrial adenocarcinoma. VEGF, Ang1, Ang2 and Tie2 expression was localized in the cytoplasm of glandular and tumor cells. The levels of each angiogenic factor were different in the phases of the menstrual cycle and each layer of normal endometrium. In general, VEGF and Tie2 expression was higher in adenocarcinoma than in normal epithelial cells. Conversely, Ang1 and Ang2 expression was higher in normal epithelium than in adenocarcinoma. The angiogenic score (CD105/CD34) tended to be higher in the adenocarcinoma than in the normal epithelium. It is suggested that the angiogenic pathway and the role of these factors seem to differ between normal tissue and carcinoma of the endometrium.
p11 Regulates extracellular plasmin production and invasiveness of HT1080 fibrosarcoma cells (2003)

The defining characteristic of a tumor cell is its ability to escape the constraints imposed by neighboring cells, invade the surrounding tissue, and metastasize to distant sites. This invasive property of tumor cells is dependent on activation of proteases at the cell surface. Most cancer cells secrete the urokinase-type plasminogen activator, which converts cell-bound plasminogen to plasmin. Here we address the issue of whether the plasminogen binding protein, p11, plays a significant role in this process. Transfection of human HT1080 fibrosarcoma cells with the human p11 gene in the antisense orientation resulted in a loss of p11 protein from the cell surface and concomitant decreases in cellular plasmin production, ECM degradation, and cellular invasiveness. The transfected cells demonstrated reduced development of lung metastatic foci in SCID mice. In contrast, HT1080 cells transfected with the p11 gene in the sense orientation displayed increased cell surface p11 protein and concomitant increases in cellular plasmin production, as well as enhanced ECM degradation and enhanced cellular invasiveness. The p11 overexpressing cells showed enhanced development of lung metastatic foci. These data establish that changes in the extracellular expression of the plasminogen receptor protein, p11, dramatically affect tumor cell-mediated pericellular proteolysis.
Cross-linking of DNA induced by chloroethyinitrosourea is prevented by O6-methyiguanine-DNA methyttransferase (1983)

The DNA repair enzyme O6-methylguanine-DNA methyltransferase has been used as a reagent to analyse the initial reaction sites of alkylating agents such as chloroethylnitrosourea that cross-link DNA. The transferase can be employed for this purpose because it removes substituted ethyl groups from DNA, as shown by its ability to act on O6-hydroxyethylguanine residues in DNA. The enzyme counteracts the formation of interstrand cross-links induced by bis-chloroethylnitrosourea, but not those induced by nitrogen mustard. Once formed, chloroethylnitrosourea-induced cross-links are not broken by the enzyme. In agreement with deductions from experiments with living cells, it is concluded that chloroethylnitrosourea act by forming reactive monoadducts at the O6 position of guanine and/or the O4 position of thymine, which subsequently generate -CH2CH2- bridges to the complementary DNA strand. A new method for quantitating interstrand cross-links in DNA has been employed.
High-Brightness Light Emitting Diodes Using Dislocation-Free Indium Gallium Nitride/Gallium Nitride Multiquantum-Well Nanorod Arrays (2004)

We demonstrate the realization of the high-brightness and high-efficiency light emitting diodes (LEDs) using dislocation-free indium gallium nitride (InGaN)/gallium nitride (GaN) multiquantum-well (MQW) nanorod (NR) arrays by metal organic-hydride vapor phase epitaxy (MO−HVPE). MQW NR arrays (NRAs) on sapphire substrate are buried in spin-on glass (SOG) to isolating individual NRs and to bring p-type NRs in contact with p-type electrodes. The MQW NRA LEDs have similar electrical characteristics to conventional broad area (BA) LEDs. However, due to the lack of dislocations and the large surface areas provided by the sidewalls of NRs, both internal and extraction efficiencies are significantly enhanced. At 20 mA dc current, the MQW NRA LEDs emit about 4.3 times more light than the conventional BA LEDs, even though overall active volume of the MQW NRA LEDs is much smaller than conventional LEDs. Moreover, the fabrication processes involved in producing MQW NRA LEDs are almost the same for conventional BA LEDs. It is, thus, not surprising that the total yield of these MQW NRA LEDs is essentially the same as that of conventional BA LEDs. The present method of utilizing dislocation-free MQW NRA LEDs is applicable to super-bright white LEDs as well as other semiconductor LEDs for improving total external efficiency and brightness of LEDs.
The Role of HOX Homeobox Genes in Normal and Leukemic Hematopoiesis (1996)

A sizable amount of new data points to a role for the HOX family of homeobox genes in hematopoiesis. Recent studies have demonstrated that HOXA and HOXB genes are expressed in human CD34+ cells, and are downregulated as cells leave the CD34+ compartment. In addition, expression of certain genes, including HOXB3 and HOXB4, is largely restricted to the long-term culture-initiating cell enriched pool, containing the putative stem cell population. Studies have also shown that HOX genes appear to be important for normal T lymphocyte and activated natural killer cell function. Overexpression of Hox-b4 in transplanted murine marrow cell results in a dramatic expansion of stem cells, while maintaining normal peripheral blood counts. In contrast, overexpression of Hox-a10 resulted in expansion of progenitor pools, accompanied by unique changes in the differentiation patterns of committed progenitors. Overexpression of Hox-a10 or Hox-b8 led to the development of myeloid leukemias, while animals transfected with marrow cells overexpressing Hox-b4 do not appear to develop malignancies. Blockade of HOX gene function using antisense oligonucleotides has revealed that several HOX genes appear to influence either myeloid or erythroid colony formation. Mice homozygous for a targeted disruption of the HOX-a9 gene show reduced numbers of granulocytes and lymphocytes, smaller spleens and thymuses, and reduced numbers of committed progenitors. These studies demonstrate that HOX homeobox genes play a role in both the early stem cell function as well as in later stages of hematopoietic differentiation, and that perturbations of HOX gene expression can be leukemogenic.
Electrochemical Ostwald Ripening of Colloidal Ag Particles on Conductive Substrates (2004)

Thermally evaporated silver nanoparticles on conducting substrates spontaneously evolve in size when immersed in pure water. The process was studied using scanning electron microscopy (SEM), energy-dispersive X-ray analysis (EDX), and optical absorption spectroscopy. The particles are proposed to reform through an electrochemical Ostwald ripening mechanism driven by the size dependence of the work function and standard electrode potential. We also discuss prior literature experiments where this process appears to occur. Our results show the sensitivity of the electrochemical properties of metallic nanoparticles at relatively large sizes (approximately 50 nm).
Effect of dexamethasone on the mean plaque size of bovine herpesvirus 1. (1985)

The effect of dexamethasone on infectious bovine rhinotracheitis virus (Bovine herpesvirus 1: BHV 1) was studied by measuring the mean plaque size produced by eight virus strains under two concentrations of dexamethasone phosphate (0.1 and 1 mM). Dexamethasone induced a significant reduction of the mean plaque size, whatever the strain used. Some differences were noted between the BHV 1 strains studied, depending on the dexamethasone concentration.
Amphiphilic Cyclic Peptoids That Exhibit Antimicrobial Activity by Disrupting Staphylococcus aureus Membranes (2013)

Abstract There is a significant unmet need for new antimicrobial agents that can address antimicrobial resistance. One promising group of antimicrobials is the antimicrobial peptides (AMPs) and their synthetic mimics. In particular, synthetic sequence‐specific oligomers of N ‐substituted glycine, termed “peptoids”, have been found to show potent antimicrobial activity against bacterial pathogens in vitro and can act against the emergence of antimicrobial resistance. In this study, we evaluate the antimicrobial activity of cyclic peptoid oligomers against clinical isolates of methicillin‐resistant Staphylococcus aureus (MRSA). The presence of the macrocyclic constraints can enforce a globally amphiphilic organization of the peptoid side‐chains. Several of these new amphiphilic compounds show potent and selective antimicrobial activity. Electron microscopy experiments demonstrate that the peptoids target and damage the MRSA cytoplasmic membrane through the formation of pores. These results substantiate the potential of peptoids as antimicrobial therapeutic agents for the treatment of S. aureus infections.
Effect of PRESS and STEAM sequences on magnetic resonance spectroscopic liver fat quantification (2009)

Measured liver fat depends on the MRS sequence used. Compared to STEAM, PRESS underestimates T2 values of fat, overestimates fat fraction, and provides a less consistent fat fraction estimate, probably due to J coupling effects.
Active Bending Catheter and Electric Endoscope Using Shape Memory Alloy (2010)

SMA materials, particularly TiNi-based alloys, have excellent mechanical properties for actuators, such as large force generation and large deformation. Technical progress has resulted in the development of many SMA micro devices. Medical applications of SMA micro actuator, namely, catheters and endoscopes are mentioned. Active catheters which have a bending mechanism using SMA wires, plates, spiral coil and meandering coil were described. And an active torsional, stiffness control mechanism and a bending mechanism for an active guide wire were described. Active bending endoscopes which have imager at the tip of bending mechanism were also mentioned. SMA micro actuators have some disadvantages such as low displacement controllability and heat generation. However, thin, soft and low cost medical steering mechanism will effective for realization of active catheters and active endoscopes which enable easy insertion, inspection and precise treatment in the human body.
MicroRNA-138 regulates osteogenic differentiation of human stromal (mesenchymal) stem cells in vivo (2011)

Elucidating the molecular mechanisms that regulate human stromal (mesenchymal) stem cell (hMSC) differentiation into osteogenic lineage is important for the development of anabolic therapies for treatment of osteoporosis. MicroRNAs (miRNAs) are short, noncoding RNAs that act as key regulators of diverse biological processes by mediating translational repression or mRNA degradation of their target genes. Here, we show that miRNA-138 (miR-138) modulates osteogenic differentiation of hMSCs. miRNA array profiling and further validation by quantitative RT-PCR (qRT-PCR) revealed that miR-138 was down-regulated during osteoblast differentiation of hMSCs. Overexpression of miR-138 inhibited osteoblast differentiation of hMSCs in vitro, whereas inhibition of miR-138 function by antimiR-138 promoted expression of osteoblast-specific genes, alkaline phosphatase (ALP) activity, and matrix mineralization. Furthermore, overexpression of miR-138 reduced ectopic bone formation in vivo by 85%, and conversely, in vivo bone formation was enhanced by 60% when miR-138 was antagonized. Target prediction analysis and experimental validation by luciferase 3' UTR reporter assay confirmed focal adhesion kinase, a kinase playing a central role in promoting osteoblast differentiation, as a bona fide target of miR-138. We show that miR-138 attenuates bone formation in vivo, at least in part by inhibiting the focal adhesion kinase signaling pathway. Our findings suggest that pharmacological inhibition of miR-138 by antimiR-138 could represent a therapeutic strategy for enhancing bone formation in vivo.
DNA Methylation Inhibitor 5-Aza-2′-Deoxycytidine Induces Reversible Genome-Wide DNA Damage That Is Distinctly Influenced by DNA Methyltransferases 1 and 3B (2007)

Genome-wide DNA methylation patterns are frequently deregulated in cancer. There is considerable interest in targeting the methylation machinery in tumor cells using nucleoside analogs of cytosine, such as 5-aza-2'-deoxycytidine (5-azadC). 5-azadC exerts its antitumor effects by reactivation of aberrantly hypermethylated growth regulatory genes and cytoxicity resulting from DNA damage. We sought to better characterize the DNA damage response of tumor cells to 5-azadC and the role of DNA methyltransferases 1 and 3B (DNMT1 and DNMT3B, respectively) in modulating this process. We demonstrate that 5-azadC treatment results in growth inhibition and G(2) arrest-hallmarks of a DNA damage response. 5-azadC treatment led to formation of DNA double-strand breaks, as monitored by formation of gamma-H2AX foci and comet assay, in an ATM (ataxia-telangiectasia mutated)-dependent manner, and this damage was repaired following drug removal. Further analysis revealed activation of key strand break repair proteins including ATM, ATR (ATM-Rad3-related), checkpoint kinase 1 (CHK1), BRCA1, NBS1, and RAD51 by Western blotting and immunofluorescence. Significantly, DNMT1-deficient cells demonstrated profound defects in these responses, including complete lack of gamma-H2AX induction and blunted p53 and CHK1 activation, while DNMT3B-deficient cells generally showed mild defects. We identified a novel interaction between DNMT1 and checkpoint kinase CHK1 and showed that the defective damage response in DNMT1-deficient cells is at least in part due to altered CHK1 subcellular localization. This study therefore greatly enhances our understanding of the mechanisms underlying 5-azadC cytotoxicity and reveals novel functions for DNMT1 as a component of the cellular response to DNA damage, which may help optimize patient responses to this agent in the future.
Tolerance to factor VIII in a transgenic mouse expressing human factor VIII cDNA carrying an Arg593 to Cys substitution (2006)

Inhibitory antibodies develop in approximately 25% of patients with severe hemophilia. A following treatment with factorVIII. In E-16KO or E-17KO mice, in which the factor VIII gene has been inactivated by insertion of a neo cassette, inhibitors develop following administration of factor VIII. Here, we describe the generation of transgenic mice expressing human factor VIII-R593C (huFVIII-R593C). Human factor VIII-R593C cDNA under control of a mouse albumin enhancer/promoter was injected into fertilized oocytes. Analysis of transgenic mice revealed that human factor VIII-R593C was expressed in the liver. Transgenic mice were crossed with factor VIII-deficient mice (E-16KO mice). In plasma of E-16KO mice antibodies were detected after five serial intravenous injections of factor VIII, while plasma of huFVIII-R593C/E-16KO mice did not contain detectable levels of antibodies. No antibody secreting cells were observed in either spleen or bone marrow of huFVIII-R593C/E-16KO mice. Also, factor VIII-specific memory B cells were not observed in the spleen of huFVIII-R593C/E-16KO mice. Analysis of T cell responses revealed that splenocytes derived of E-16KO mice secreted IL-10 and IFN-gamma following restimulation with factor VIII in vitro. In contrast, no factor VIII-specific T cell responses were observed in huFVIII-R593C/E-16KO mice. These results indicate that huFVIII-R593C/E-16KO mice are tolerant to intravenously administered factor VIII. It is anticipated that this model may prove useful for studying immune responses in the context of factor VIII gene therapy.
Preexisting Immunity and Low Expression in Primates Highlight Translational Challenges for Liver-directed AAV8-mediated Gene Therapy (2010)

Liver-directed gene therapy with adeno-associated virus (AAV) vectors effectively treats mouse models of lysosomal storage diseases (LSDs). We asked whether these results were likely to translate to patients. To understand to what extent preexisting anti-AAV8 antibodies could impede AAV8-mediated liver transduction in primates, commonly preexposed to AAV, we quantified the effects of preexisting antibodies on liver transduction and subsequent transgene expression in mouse and nonhuman primate (NHP) models. Using the highest viral dose previously reported in a clinical trial, passive transfer of NHP sera containing relatively low anti-AAV8 titers into mice blocked liver transduction, which could be partially overcome by increasing vector dose tenfold. Based on this and a survey of anti-AAV8 titers in 112 humans, we predict that high-dose systemic gene therapy would successfully transduce liver in >50% of human patients. However, although high-dose AAV8 administration to mice and monkeys with equivalent anti-AAV8 titers led to comparable liver vector copy numbers, the resulting transgene expression in primates was ~1.5-logs lower than mice. This suggests vector fate differs in these species and that strategies focused solely on overcoming preexisting vector-specific antibodies may be insufficient to achieve clinically meaningful expression levels of LSD genes using a liver-directed gene therapy approach in patients.
Characterization of the TAC box, acis‐element within an elicitor‐inducible sesquiterpene cyclase promoter (1998)

Summary The first unique step in the synthesis of the tobacco phytoalexin capsidiol is cyclization of farnesyl pyrophosphate catalyzed by 5‐epi‐aristolochene synthase (EAS), a sesquiterpene cyclase. Earlier work demonstrated that the elicitor‐inducibility of this enzyme activity corresponded to the transcriptional activation of at least one gene, EAS4 , of a rather complex gene family consisting of &gt; 10 members. To investigate the mechanism(s) controlling expression of this gene, fragments of the EAS4 promoter were examined for binding by proteins in nuclear and whole‐cell extracts. A strong protein binding site (TAC box; ACTCTACAGTACTC) was identified between –245 and –232 by the electrophoretic mobility shift assay, and DNAase I and methylation interference footprinting. Several distinctly migrating bands representing protein–TAC box complexes were also observed in the mobility shift assays, and the relative abundance of these bands varied in extracts from cells at different stages of EAS induction. The TAC box binding factor (TacBBF) was purified &gt; 450‐fold from crude whole‐cell extracts by a combination of DNA affinity and cation exchange chromatography. The purified fractions were enriched for polypeptides of 17 and 19 kDa and the DNA binding properties of these preparations were characterized. Mutation of 2 bp in the TAC box prevented protein binding in vitro and increased both basal and elicitor‐inducible gene expression 2.5‐fold in transgenic tobacco plants harboring promoter–GUS fusions, consistent with the notion that this cis ‐element functions as a silencer or repressor of EAS gene expression.
Volterra series and Picard iteration for nonlinear circuits and systems (1978)

Two methods of analyzing nonlinear circuits and systems are iteration and Volterra series. This paper shows the relation between the two methods and gives a means of calculating Volterra kernels in the time domain.
G h : a GTP-Binding Protein with Transglutaminase Activity and Receptor Signaling Function (1994)

The alpha 1-adrenergic receptors activate a phospholipase C enzyme by coupling to members of the large molecular size (approximately 74 to 80 kilodaltons) G alpha h family of guanosine triphosphate (GTP)-binding proteins. Rat liver G alpha h is now shown to be a tissue transglutaminase type II (TGase II). The transglutaminase activity of rat liver TGase II expressed in COS-1 cells was inhibited by the nonhydrolyzable GTP analog guanosine 5'-O-(3-thiotriphosphate) or by alpha 1-adrenergic receptor activation. Rat liver TGase II also mediated alpha 1-adrenergic receptor stimulation of phospholipase C activity. Thus, G alpha h represents a new class of GTP-binding proteins that participate in receptor signaling and may be a component of a complex regulatory network in which receptor-stimulated GTP binding switches the function of G alpha h from transglutamination to receptor signaling.
Microbial community profiling of peripheral blood in myalgic encephalomyelitis/chronic fatigue syndrome (2018)

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is estimated to afflict hundreds of thousands, if not millions, of Americans with vastly more impacted individuals worldwide; however, the etiology of this disease has not been well established. Based on the features of ME/CFS, we hypothesized an unrecognized vascular infection may be involved. To evaluate this possibility, we performed a blinded pilot study of 30 ME/CFS patients meeting the Fukuda criteria and 48 normal controls. A community-wide analysis using next-generation DNA sequencing methods detected prokaryotic and eukaryotic populations in the peripheral blood of both ME/CFS patients and normal controls. Analysis of the prokaryotic portion of the samples revealed that organisms belonging to the Pseudomonas asplenii species, Pseudomonadaceae family, Pseudomonadales order, and γ-proteobacteria class are inversely correlated with RAND-36 scores, a quality of life metric that is reduced in ME/CFS patients. In addition, analysis of the detected eukaryotic species suggests that the Perkinsus genus is also inversely associated with RAND-36 scores. The most frequently observed eukaryotic DNA was for Funneliformis mosseae, an arbuscular mycorrhizal fungus, which was in both ME/CFS and normal control samples. A multivariate composite score consisting of the Perkinsus genus, Spumella genus, and β-proteobacteria class displays an inverse relationship to RAND-36 scores. Lastly, the combined measurements of several taxa allow for a retrospective categorical sorting of ME/CFS patients from normal control samples. These results suggest that microbial DNA signatures, including those from poorly understood eukaryotes, may be differentially detectable in ME/CFS and normal control samples.
Choosing the right cell line for breast cancer research (2011)

Breast cancer is a complex and heterogeneous disease. Gene expression profiling has contributed significantly to our understanding of this heterogeneity at a molecular level, refining taxonomy based on simple measures such as histological type, tumour grade, lymph node status and the presence of predictive markers like oestrogen receptor and human epidermal growth factor receptor 2 (HER2) to a more sophisticated classification comprising luminal A, luminal B, basal-like, HER2-positive and normal subgroups. In the laboratory, breast cancer is often modelled using established cell lines. In the present review we discuss some of the issues surrounding the use of breast cancer cell lines as experimental models, in light of these revised clinical classifications, and put forward suggestions for improving their use in translational breast cancer research.