gebhart/patrepeval huggingface dataset:
Gene Expression Profiles Predict Sensitivity of Prostate Cancer to Radiotherapy (2013)

Ionizing radiation (IR) is the most common treatment used to control localized primary prostate cancer (PC). However, for a significant number of patients, radiotherapy fails to adequately control the tumor. Thus, a main clinical problem today is the lack of a specific marker that may be used to predict the treatment outcome and to identify prostate cancer patients who are unlikely to respond to radiation therapy. In this study, we used human PC xenografts with predetermined radioresistant/sensitive phenotypes, and gene expression microarrays, correlated their specific transcripttional profiles with response to radiation. Employing unsupervised two-way hierarchical clustering, we identified four gene clusters displaying different expression patterns. Two clusters showed higher expression levels in the resistant xenografts and the other two clusters showed higher expression levels in the sensitive xenografts. Expression levels of 113 genes differed by at least 3 fold between sensitive and resistant xenografts. These genes represent members of several cellular pathways, some of which are known to be associated with response to radiation. All or several of these genes could serve as predictive tools to determine at biopsy the expected response of a particular tumor to radiotherapy. Indeed, the profiles we identified enabled us to predict the degree of radiosensitivity of a panel of established PC cell lines. Importantly, irradiation of the PC xenografts did not induce any significant changes in gene expression, regardless of their susceptibility phenotype. These data strongly support the first of two models: a: a random effect of irradiation on a homogeneous population of cells, rather than b: of a tumor comprised of a mixture of radioresistant and radiosensitive cell subpopulations. Our findings imply that each of the radio-phenotypes represents different intrinsic characteristics that affect the ability of a tumor to survive radiotherapy.
Mussel Inspired Coating of a Biocompatible Cyclodextrin Based Polymer onto CoCr Vascular Stents (2014)

During the past decade, drug-eluting stents (DES) have been widely used for the treatment of occlusive coronary artery diseases. They are supposed to reduce the incidence of early in-stent restenosis by the elution of highly hydrophobic antiproliferative drugs. Nevertheless, the absence of long-term activity of these devices is responsible for late acute thrombosis probably due to the delayed re-endothelialization of the arterial wall over the bare metallic stent struts. Thus, a new generation of DES with a sustained release of therapeutic agents is required to improve long-term results of these devices. In this article, we report an original functionalization of CoCr vascular devices with a hydrophilic, biocompatible and biodegradable cyclodextrins based polymer which acts as a reservoir for lipophilic drugs allowing the sustained release of antiproliferative drugs. In this setting, polydopamine (PDA), a strong adhesive biopolymer, was applied as a first coating layer onto the surface of the metallic CoCr device in order to promote the strong anchorage of a cyclodextrin polymer. This polymer was generated "in situ" from the methylated cyclodextrins and citric acid as a cross-linking agent through a polycondensation reaction. After optimization of the grafting process, the amount of cyclodextrin polymer coated onto the CoCr device was quantified by colorimetric titrations and the resulting film was characterized by scanning electron microscopy (SEM) investigations. The cytocompatibility of the resulting coated film was assessed by cell proliferation and vitality tests. Finally, the ability of this coated device to act as a drug-eluting system was evaluated with paclitaxel, a strong hydrophobic antiproliferative drug, a reference drug used in current vascular drug-eluting stents.
Inflammation and Cancer III. Somatostatin and the innate immune system (2004)

In the stomach, somatostatin is secreted from D cells and is a potent inhibitor of gastrin-induced acid secretion. During bacterial infection, somatostatin expression and release are suppressed. As a result, gastric infection often induces hypergastrinemia that, in turn, stimulates gastric acid secretion, the stomach's most important antimicrobial agent. There are an abundance of data showing that inflammatory cytokines regulate somatostatin in immune and neural cells. However, it was not until recently that the immunoregulation of gastric somatostatin was studied in vivo. This theme article discusses the role of somatostatin as an immunoregulatory peptide during gastritis.
Metal cluster plasmons analyzed by energy-resolved photoemission (2022)

The optical response of size-selected metal clusters is studied by wavelength-dependent photoemission and energy-resolved photoelectron detection. Relative photodetachment cross sections giving information on the plasmon are determined for the example of closed-shell Ag<sub>91</sub><sup>-</sup>. Notably, the peak energy of this anion (3.74 eV) is higher than the small particle limit in Mie theory of 3.5 eV. Different methods to extract cross sections from the spectra are applied. In particular, we compare the results obtained by integrating the full electron yields to analyses based on evaluating specified binding energy windows. The approach opens up new possibilities to conduct studies on Landau fragmentation as a result of multielectron excitations.
Gpr161 anchoring of PKA consolidates GPCR and cAMP signaling (2016)

Scaffolding proteins organize the information flow from activated G protein-coupled receptors (GPCRs) to intracellular effector cascades both spatially and temporally. By this means, signaling scaffolds, such as A-kinase anchoring proteins (AKAPs), compartmentalize kinase activity and ensure substrate selectivity. Using a phosphoproteomics approach we identified a physical and functional connection between protein kinase A (PKA) and Gpr161 (an orphan GPCR) signaling. We show that Gpr161 functions as a selective high-affinity AKAP for type I PKA regulatory subunits (RI). Using cell-based reporters to map protein-protein interactions, we discovered that RI binds directly and selectively to a hydrophobic protein-protein interaction interface in the cytoplasmic carboxyl-terminal tail of Gpr161. Furthermore, our data demonstrate that a binary complex between Gpr161 and RI promotes the compartmentalization of Gpr161 to the plasma membrane. Moreover, we show that Gpr161, functioning as an AKAP, recruits PKA RI to primary cilia in zebrafish embryos. We also show that Gpr161 is a target of PKA phosphorylation, and that mutation of the PKA phosphorylation site affects ciliary receptor localization. Thus, we propose that Gpr161 is itself an AKAP and that the cAMP-sensing Gpr161:PKA complex acts as cilium-compartmentalized signalosome, a concept that now needs to be considered in the analyzing, interpreting, and pharmaceutical targeting of PKA-associated functions.
Enhancing Effect of Low Culture Temperature on Specific Antibody Productivity of Recombinant Chinese Hamster Ovary Cells: Clonal Variation (2004)

To understand the different responses of recombinant Chinese hamster ovary (rCHO) cells to low culture temperature regarding specific productivity (q), 12 parental clones and their corresponding amplified clones producing a humanized antibody were cultivated at 32 and 37 degrees C. The specific growth rate of all clones, including both parental and amplified clones, decreased by 30-63% at 32 degrees C, compared to rates at 37 degrees C. In contrast, their specific antibody productivity (qAb) was significantly enhanced at 32 degrees C. Furthermore, the degree of qAb enhancement at 32 degrees C varied a lot from 4- to 25-fold among the parental clones. At 32 degrees C, most of the amplified clones, regardless of methotrexate (MTX) levels, also showed enhanced qAb but to a lesser extent than their parental clones. However, clone 14 amplified at 0.32 microM MTX (clone 14-0.32) and clone 20 amplified at 1 microM MTX (clone 20-1.00), unlike their parental clones, did not show enhanced qAb at 32 degrees C. Thus, it was found that the enhancing effect of low culture temperature on q of rCHO cells depends on clones. Taken together, the results obtained here emphasize the importance of clonal selection for the successful application of low culture temperature to the enhanced foreign protein production in rCHO cells.
Characteristic and Mechanism of Methane Dehydroaromatization over Zn-Based/HZSM-5 Catalysts under Conditions of Atmospheric Pressure and Supersonic Jet Expansion (2011)

The catalytic performance of Zn-based/HZSM-5 catalysts prepared by wet impregnation method was investigated for the methane dehydroaromatization (MDA) reaction under the conditions of atmospheric pressure and supersonic jet expansion (SJE). The physical properties of the catalysts were characterized by Brunauer–Emmett–Teller (BET), Fourier transform infrared (FT-IR), temperature-programmed reduction of H2 (H2-TPR), temperature-programmed desorption of NH3 (NH3-TPD), X-ray photoelectron spectroscopy (XPS), thermogravimetric and differential thermogravimetric (TG/DTG), and high-resolution transmission electron microscopy (HRTEM) techniques. The results revealed that under SJE condition the Zn/HZSM-5 catalyst exhibited high catalytic activity. It was found that because of the rapid migration of H+ ions on the catalyst, the activation of CH4 at active sites of nano-ZnO is facile. A new reaction mechanism that involves an active “ZnO–CH3+...–HZnO” intermediate formed as a result of synergetic action between ZnO and HZSM-5 has been proposed for CH4 dissociation and dehydrogenation. Under atmospheric pressure, however, the catalytic activity of Zn/HZSM-5 is low.
Anti-PD1 ‘SHR-1210ʹ aberrantly targets pro-angiogenic receptors and this polyspecificity can be ablated by paratope refinement (2018)

Monoclonal anti-programmed cell death 1 (PD1) antibodies are successful cancer therapeutics, but it is not well understood why individual antibodies should have idiosyncratic side-effects. As the humanized antibody SHR-1210 causes capillary hemangioma in patients, a unique toxicity amongst anti-PD1 antibodies, we performed human receptor proteome screening to identify nonspecific interactions that might drive angiogenesis. This screen identified that SHR-1210 mediated aberrant, but highly selective, low affinity binding to human receptors such as vascular endothelial growth factor receptor 2 (VEGFR2), frizzled class receptor 5 and UL16 binding protein 2 (ULBP2). SHR-1210 was found to be a potent agonist of human VEGFR2, which may thereby drive hemangioma development via vascular endothelial cell activation. The v-domains of SHR-1210's progenitor murine monoclonal antibody 'Mab005' also exhibited off-target binding and agonism of VEGFR2, proving that the polyspecificity was mediated by the original mouse complementarity-determining regions (CDRs), and had survived the humanization process. Molecular remodelling of SHR-1210 by combinatorial CDR mutagenesis led to deimmunization, normalization of binding affinity to human and cynomolgus PD1, and increased potency in PD1/PD-L1 blockade. Importantly, CDR optimization also ablated all off-target binding, rendering the resulting antibodies fully PD1-specific. As the majority of changes to the paratope were found in the light chain CDRs, the germlining of this domain drove the ablation of off-target binding. The combination of receptor proteome screening and optimization of the antibody binding interface therefore succeeded in generating novel, higher-potency, specificity-enhanced therapeutic IgGs from a single, clinically sub-optimal progenitor. This study showed that highly-specific off-target binding events might be an under-appreciated phenomenon in therapeutic antibody development, but that these unwanted properties can be fully ameliorated by paratope refinement.
Response to Fructose Likely Does Have a Role in Hypertension (2012)

We thank Madero et al 1 for their letter regarding our systematic review and meta-analysis of the effect of fructose on blood pressure (BP). The fructose moiety of sucrose and high-fructose corn syrup has been singled out as the main dietary driver of cardiometabolic disease. We, therefore, designed our systematic review to isolate the effect of fructose intake on BP relative to other carbohydrates. To this end, we did not include trials in which fructose was administered as sucrose or high-fructose corn syrup, unless these sweeteners were the comparators. As comparators, we found that sucrose and high-fructose corn syrup behaved no differently than fructose. 1 Furthermore, to assess the effect of naturally occurring fructose, we also included the study by Madero et al, 3 in which fruit was the main fructose source. Despite the concerns that it might skew the results of our systematic review, sensitivity analyses did not identify this trial as a confounder. Fructose may certainly have a BPraising effect in acute postprandial studies; however, we were interested in the fructose effect on fasting BP, because this is the outcome that has been related to cardiovascular events and mortality in clinical trials and cohort studies. Office BP measurements remain the basis for entry criteria and targets and are the therapeutic end points in clinical practice guidelines. inally, the uric acid story is certainly an interesting one, especially the study by Perez-Pozo et al, Unfortunately, it is difficult to conclude that the effects were particular to fructose and not to energy, because there was no carbohydrate comparator, and fructose provided excess energy (24% total energy) at doses 2 times the 95 th percentile for US intake 1 (200 g/d). Interestingly, data from the Harvard cohorts show no association between fructose and hypertension at normally consumed levels. To address this issue, we have undertaken a systematic review and meta-analysis of controlled feeding trials to address a uric acid mechanism. We found that, although fructose under hypercaloric feeding conditions increased uric acid relative to a control diet alone, it did not under isocaloric feeding conditions. The suggestion is that energy remains an important confounder in any discussion of the physiology of fructose in hypertension.
Two cases of hypothyroidism due to chronic thyroiditis preceding thyrotoxic Graces' disease. (1986)

慢性甲状腺炎による甲状腺機能低下症の治療中にBasedow病を発症した2症例を報告した.症例1は39才,症例2は46才の女性で,両者の血清T4, T3および症例1の131I摂取率は正常であつたが,血清TSHが高値であり,抗サイログロブリン抗体,および抗マイクロゾーム抗体が陽性のため,慢性甲状腺炎に伴うsubclinical hypothyroidismとしてl-thyroxineを投与していた.それぞれ2年半および1年後に, T4およびT3が高値となり, l-thyroxineを中止後も高値を持続した. 131I摂取率も高値となり, T3の投与にても抑制されず,ともにBasedow病を発症したものと思われた.症例2では眼症状も認められた.またこれらの例ではTSHリセプター抗体が陽性であつた.
P‐60: Novel Display Image Quality Analysis Based on Human Visual Perception (2007)

Abstract Picture quality analysis technologies considering on human visual perception (HVP) were introduced. Dynamic contrast analysis method in moving contents, color aberration analysis method, ghost image assessment method, and outdoor picture quality assessment method were researched and reviewed. The results from those analysis methods was correlated with human visual perception.
Optimization of resolution-enhanced photolithography for a 256 Mb DRAM cell (2002)

An approach for design-specific lithography optimization using simulation and experimental validation has been demonstrated for a 256 Mb DRAM cell. Results from this study indicate that the optimum lithographic solution has a strong dependence on pattern shape and density. Initial emphasis in the implementation of resolution-enhancement techniques should be placed on the development of attenuated phase-shifting masks as well as off-axis illumination. These efforts must continue to strive towards extending lithographic performance beyond current capabilities at 0.25 /spl mu/m groundrules.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Germline alterations in the CDH1 gene in familial gastric cancer in the Japanese population (2011)

Germline point or small frameshift mutations of the CDH1 (E-cadherin) gene are known to cause familial gastric cancer (FGC), but the frequency of CDH1 mutations is low in Japanese patients with FGC. Because recent studies have reported germline large genomic deletions of CDH1 in European and Canadian patients with FGC, in the present study we examined DNA samples from 13 Japanese patients with FGC to determine whether similar germline changes were present in CDH1 in this population. Using a sequencing analysis, a 1-bp deletion (c.1212delC), leading to the production of a truncated protein (p.Asn405IlefsX12), was found in an FGC family; immunohistochemical analysis revealed the loss of CDH1 protein expression in the tumors in this family. Using a combination of multiplex ligation-dependent probe amplification (MLPA) and RT-PCR analyses, we also found a large genomic deletion (c.164-?_387+?del), leading to the loss of exon 3 and the production of a truncated protein (p.Val55GlyfsX38), in another FGC family. The functional effects of the detected mutations were examined using a slow aggregation assay. Significant impairment of cell-cell adhesion was detected in CHO-K1 cells expressing Ile405fsX12- and Gly55fsX38-type CDH1 compared with cells expressing wild-type CDH1. Our results suggest that the p.Asn405IlefsX12 and p.Val55GlyfsX38 mutations of the CDH1 gene contribute to carcinogenesis in patients with FGC. This is the first report of CDH1 germline truncating mutations in Japanese patients with FGC. Screening for large germline rearrangements should be included in CDH1 genetic testing for FGC.
Enrichment of murine bone marrow natural suppressor activity in the fraction of hematopoietic progenitors with interleukin 3 receptor-associated antigen. (1992)

Natural suppressor (NS) activity has been identified in several sites of active hematopoiesis. In this study we characterized NS activity in murine bone marrow (BM) using monoclonal antibodies (mAbs) to interleukin 3 (IL-3) receptor-associated antigen (IL-3RAA) and various cytokines that exert a strong influence on hematopoiesis or lymphocyte interaction. NS activity of BM cells of relatively low density was enhanced by IL-3 or granulocyte-macrophage colony-stimulating factor (GM-CSF). When the BM cells were separated into IL-3RAA+ cells and IL-3RAA- cells, the IL-3RAA+ cells demonstrated potent NS activity, whereas IL-3RAA- cells had either no or weak NS activity. The IL-3RAA+ cells showed non-T- and non-B-cell phenotype and had high affinity to wheat germ agglutinin (WGA), a marker for hematopoietic progenitors. In assays for hematopoietic activity, it appeared that the early differentiating progenitors (day 8 spleen colony-forming units [CFU-S], granulocyte-macrophage colony-forming units [CFU-GM]) were enriched in the IL-3RAA+ cell population, whereas more immature multipotent progenitors (day 12 CFU-S, granulocyte erythrocyte macrophage megakaryocyte colony-forming units [CFU-GEMM]) were contained in the IL-3RAA- cell population. Both suppressor cells and IL-3RAA+ cells spontaneously developed from the IL-3RAA- cell population. These findings suggest that NS cells in murine BM are early hematopoietic progenitors and are probably committed to the myeloid lineage. Hybridoma cells established between the IL-3RAA+ cells and BW5147 cells produced suppressor factor(s). This finding suggests that the NS cells produce soluble mediator(s) that may be responsible for their suppressive action.
ChemInform Abstract: DIE RK. VON ORGANOBORANEN, DIE EINE TERT. ALKYLGRUPPE ENTHALTEN, MIT KOHLENMONOXID, EIN NEUER WEG ZUR SYNTH. VON HOCH VERZWEIGTEN TRIALKYLCARBINOLEN (1972)

Abstract tert.‐Alkyl‐dialkyl‐borane.
Stereoselective Synthesis of L-[1-13C], L-[2-13C] and L-[15N] Amino Acids (1996)

Abstract The precursor N-(diphenylmethylene) glycinyl camphor sultam has been specifically labelled by nitrogen-15 or carbon-13 starting from either NH4Cl, K2 13CO3 or 13CH3NH2 or labelled glycine. Akylation of these different labelled precursors by corresponding electrophiles yielded the following labelled amino acids: Leu, Phe, Ala, Val, Ser, Asn, Gln, Asp, Trp and Cys.
Class 1 Reversibly Glycosylated Polypeptides Are Plasmodesmal-Associated Proteins Delivered to Plasmodesmata via the Golgi Apparatus (2005)

Abstract SE-WAP41, a salt-extractable 41-kD wall-associated protein that is associated with walls of etiolated maize (Zea mays) seedlings and is recognized by an antiserum previously reported to label plasmodesmata and the Golgi, was cloned, sequenced, and found to be a class 1 reversibly glycosylated polypeptide (C1RGP). Protein gel blot analysis of cell fractions with an antiserum against recombinant SE-WAP41 showed it to be enriched in the wall fraction. RNA gel blot analysis along the mesocotyl developmental axis and during deetiolation demonstrates that high SE-WAP41 transcript levels correlate spatially and temporally with primary and secondary plasmodesmata (Pd) formation. All four of the Arabidopsis thaliana C1RGP proteins, when fused to green fluorescent protein (GFP) and transiently expressed in tobacco (Nicotiana tabacum) epidermal cells, display fluorescence patterns indicating they are Golgi- and plasmodesmal-associated proteins. Localization to the Golgi apparatus was verified by colocalization of transiently expressed AtRGP2 fused to cyan fluorescence protein together with a known Golgi marker, Golgi Nucleotide Sugar Transporter 1 fused to yellow fluorescent protein (GONST1:YFP). In transgenic tobacco, AtRGP2:GFP fluorescence is punctate, is present only in contact walls between cells, and colocalizes with aniline blue–stained callose present around Pd. In plasmolyzed cells, AtRGP2:GFP remains wall embedded, whereas GONST1:YFP cannot be found embedded in cell walls. This result implies that the targeting to Pd is not due to a default pathway for Golgi-localized fusion proteins but is specific to C1RGPs. Treatment with the Golgi disrupting drug Brefeldin A inhibits Pd labeling by AtRGP2:GFP. Integrating these data, we conclude that C1RGPs are plasmodesmal-associated proteins delivered to plasmodesmata via the Golgi apparatus.
Nitrate transport in intact wheat roots:II. Long-term effects of NO3−concentration in the nutrient solution on NO3−unidirectional fluxes and distribution within the tissues5 (1994)

We have examined the long-term effects of NO3− concentrations on NO3− (15NO3−) fluxes and cellular pool sizes in roots of intact 30-d-old wheat (Triticum aestivum cv. Courtot) grown hydroponically. Compartmental analysis was performed under steady-state conditions at five different levels of NO3− concentration (from 0.1 up to 5 mol m−3 taking into account metabolism and secretion into the xylem (Devienne et al., 1994). Nitrate and reduced nitrogen levels in the tissues were largely independent of external NO3− concentration although below 1.5 mol m−3 NO3−; concentration limited plant growth. In the chamber, marked diurnal variations in net uptake occurred and, in the light, higher NO3− concentrations yielded higher NO3− uptake rates. After transfer of the plants to the laboratory, the increase in net uptake linked to elevation of NO3−; concentrations was even larger (from 0.1 to 8.8μmol h−1 g−1 FW) as a result of a marked increase (× 10–11) in the unidirectional influx at the plasmalemma while NO3− efflux was less enhanced (× 4–5). Under these conditions, influx into the vacuole was also higher (× 2–4) while efflux from the vacuole was little affected (× 1–3). NO3− concentrations within the cell compartments were estimated under the clas sical assumptions. The vacuolar concentration was a little modified by NO3− availability whereas that in the cytosol increased from about 10 mol m−3 to about 20 mol m−3 indicating that (1) the absolute value for the cytosol was high and (2) it displayed only a small increase despite very large changes in NO3− fluxes. NO3− distribution within the cells did not seem to involve an active accumulation of NO3− in the vacuole.