gebhart/patrepeval huggingface dataset:
MANGIFERIN; A NATURAL GLUCOSYLXANTHONE WITH MULTIPLES PHARMACOLOGICAL ACTIONS ALSO EFFECTIVE IN CANCER CHEMOPREVENTION (2018)

Introduction: Cancer is a multigenic disease associated to chronic inflammation, which in turn is associated to oxidative stress and neuropathic pain. The main problems of the anti-cancer chemotherapy are their lack of specificity and their serious adverse effects. The identification of biologically active compound from natural products has been a long-term focus in the pharmaceutical industry. The natural compounds capable of increasing the defenses of the human organism should at least, diminish the adverse effects of classical anticancer drugs. Mangiferin is an antioxidant glucosylxanthone, which has been known for its immunomodulatory, antitumoral and anti-inflammatory actions. Material and Methods: In this way, we apply bioinformatics methods to identify multiple targets of the gene expression profiles analysis following in vivo treatment. By using transcriptome based pathway analysis, it was possible to identify activated or repressed pathways and to predict possible molecular targets in CT-26.WT murine colon carcinoma syngeneic tumor models. Results and Discussion: The antitumor and antimetastatic effects were positively correlated with increasing doses of mangiferin, showing the greatest effect at 100 mg/kg. Pathway enrichment analysis revealed that mangiferin targeted specific cancer processes related to cell death and survival, cellular growth and proliferation, inflammatory and oxidative response. In this work some results of studies guided to increase the bio-availability of the mangiferin with the objective to obtain more effective, bioavailable and safe pharmaceutical forms are also shown. Conclusions: Mangiferin holds promise as an effective antitumor agent by triggering antimetastatic and antiangiogenic effects.
Scaffolds between MT2 melatonin receptors, Gi, βarrestins, MEK and ERK form in differentiating bone stem cells and these processes require internalization; domains found in the C‐tail of the receptor (2007)

Melatonin induces bone stem cell differentiation into osteoblasts dependent upon desensitized MT 2 receptors (MT 2 R), internalization processes and MEK (1/2). Since GPCRs can modulate MEK/ERK (1/2) through a β‐arrestin‐dependent pathway, the objectives of this study were (1) to assess if scaffolds between MT 2 R, G‐proteins, β‐arrestins, and MEK and ERK (1/2) could form in the bone stem cell using immunoprecipitation analysis, (2) to determine if melatonin could still modulate ERK translocation in the cell even if MT 2 R are desensitized using immunocytochemistry and (3) to determine the MT 2 R domains involved with its desensitization using mutagenesis. Our results show that human MT 2 R scaffold with β arrestins, and MEK/ERK (1/2) that are blocked in the presence of luzindole. Our data also show that melatonin can promote ERK translocation from the cytoplasm to the nucleus even if all other measures suggest that the MT 2 R are desensitized. Also, our data show that truncation mutations in the C‐tail of MT 2 R (MT 2 Y7.64GFP) prevent melatonin‐induced MT 2 R internalization. Perhaps, the C‐tail functions to internalize these MT 2 R/β‐arrestin scaffolds to activate ERK and thus promote melatonin‐induced bone stem cell differentiation into an osteoblast. This study was supported by the Pennsylvania Health Assessment Fund awarded to PWE, and the AFPE fellowship awarded to NMR
Bioaccessibility tests accurately estimate bioavailability of lead to quail (2016)

Hazards of soil-borne lead (Pb) to wild birds may be more accurately quantified if the bioavailability of that Pb is known. To better understand the bioavailability of Pb to birds, the authors measured blood Pb concentrations in Japanese quail (Coturnix japonica) fed diets containing Pb-contaminated soils. Relative bioavailabilities were expressed by comparison with blood Pb concentrations in quail fed a Pb acetate reference diet. Diets containing soil from 5 Pb-contaminated Superfund sites had relative bioavailabilities from 33% to 63%, with a mean of approximately 50%. Treatment of 2 of the soils with phosphorus (P) significantly reduced the bioavailability of Pb. Bioaccessibility of Pb in the test soils was then measured in 6 in vitro tests and regressed on bioavailability: the relative bioavailability leaching procedure at pH 1.5, the same test conducted at pH 2.5, the Ohio State University in vitro gastrointestinal method, the urban soil bioaccessible lead test, the modified physiologically based extraction test, and the waterfowl physiologically based extraction test. All regressions had positive slopes. Based on criteria of slope and coefficient of determination, the relative bioavailability leaching procedure at pH 2.5 and Ohio State University in vitro gastrointestinal tests performed very well. Speciation by X-ray absorption spectroscopy demonstrated that, on average, most of the Pb in the sampled soils was sorbed to minerals (30%), bound to organic matter (24%), or present as Pb sulfate (18%). Additional Pb was associated with P (chloropyromorphite, hydroxypyromorphite, and tertiary Pb phosphate) and with Pb carbonates, leadhillite (a lead sulfate carbonate hydroxide), and Pb sulfide. The formation of chloropyromorphite reduced the bioavailability of Pb, and the amendment of Pb-contaminated soils with P may be a thermodynamically favored means to sequester Pb. Environ Toxicol Chem 2016;35:2311-2319. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US Government work and, as such, is in the public domain in the United States of America.
<i>Neisseria gonorrhoeae</i>: Drug Resistance, Mouse Models, and Vaccine Development (2017)

Gonorrhea, an obligate human infection, is on the rise worldwide and gonococcal strains resistant to many antibiotics are emerging. Appropriate antimicrobial treatment and prevention, including effective vaccines, are urgently needed. To guide investigation, an experimental model of genital tract infection has been developed in female mice to study mechanisms by which Neisseria gonorrhoeae evades host-derived antimicrobial factors and to identify protective and immunosuppressive pathways. Refinements of the animal model have also improved its use as a surrogate host of human infection and accelerated the testing of novel therapeutic and prophylactic compounds against gonococcal infection. Reviewed herein are the (a) history of antibiotic usage and resistance against gonorrhea and the consequences of resistance mechanisms that may increase gonococcal fitness and therefore the potential for spread, (b) use of gonococcal infection in the animal model system to study mechanisms of pathogenesis and host defenses, and
Regulation of immune reactivity to collagen in human beings (1981)

Denaturated beef collagen was tested for its ability to induce the production of leukocyte inhibition factor among the peripheral blood mononuclear cells from patients with rheumatoid arthritis and normal individuals. Responsiveness, defined as the production of leukocyte inhibition factor sufficient to cause greater than 20% inhibition of leukocyte migration, was significantly (P less than 0.001, X2 = 31.1) associated with HLA-DR4. All HLA-DR4 positive individuals, including subjects without any evidence of synovitis, were collagen responders. There was no significant (P = 0.3) difference in the absolute reactivity of HLA-DR4+ versus HLA-DR4- individuals to respond to another antigen, Candida albicans. Collagen reactivity required interactions between macrophages and T cells and was directed against determinants inherent in the linear polypeptide, (Gly-Pro)n. In 5 normal HLA-DR4- nonresponders tested, absence of discernable reactivity to collagen was associated with the presence of antigen-specific, radiosensitive suppressive T cells. These studies suggest that during the physiologic metabolism of collagen all individuals are exposed to Gly-Pro determinants normally buried in the interstices of the collagen triple helix. In individuals whose major histocompatibility complex contains genes linked to those coding for HLA-DR4, this results in the activation of reactive T cells. Conversely, in individuals lacking these genes, collagen-specific suppressive cells predominate.
JNK/ERK/FAK Mediate Promigratory Actions of Basic Fibroblast Growth Factor in Astrocytes via CCL2 and COX2 (2011)

While the role of cytokines in causing pro- and anti-inflammatory cascades in the brain and that of chemokines in promoting chemotaxis is well recognized, the immunomodulatory actions of neurotrophins released during brain injury remains largely undetermined. This knowledge gap affects basic fibroblast growth factor (FGF2), which in the brain is mainly produced by astrocytes and characteristically upregulated in reactive astrocytes. The goal of this study was to characterize the inflammatory actions of FGF2 in astrocytes using primary cultures. We report that FGF2 induced the upregulation of monocyte chemoattractant protein (CCL2) and cyclo-oxygenase type 2 (COX2), and the inhibition of lipopolysaccharide-elicited ICAM1 upregulation. The effects of FGF2 were: (i) dependent on gene transcription as revealed by the concomitant regulation of CCL2 or ICAM1 mRNAs; (ii) mediated by the FGF2 receptor type 2; (iii) dependent on ERK, JNK and FAK, and (iv) NF-κB-independent. FGF2 also caused accelerated wound closure dependent on CCL2, COX2, ERK, JNK and FAK in a scratch assay. We conclude that the signaling network triggered by FGF2 in astrocytes converged into accelerating directed motion. It follows that astrocyte migration to injury sites may be a key factor in the repair mechanisms orchestrated by FGF2.
CD40 Signals Apoptosis through FAN-regulated Activation of the Sphingomyelin-Ceramide Pathway (1999)

The possibility that the sphingomyelin (SM)-ceramide pathway is activated by CD40, a transmembrane glycoprotein belonging to the tumor necrosis factor receptor superfamily and that plays a critical role in the regulation of immune responses has been investigated. We demonstrate that incubation of Epstein-Barr virus-transformed lymphoid cells with an anti-CD40 antibody acting as an agonist results in the stimulation of a neutral sphingomyelinase, hydrolysis of cellular SM, and concomitant ceramide generation. In addition, SM degradation was observed in acid sphingomyelinase-deficient cells, as well as after ligation by soluble CD40 ligand. The anti-CD40 antibody, as well as the soluble CD40 ligand induced a decrease in thymidine incorporation and morphological features of apoptosis, which were mimicked by cell-permeant or bacterial sphingomyelinase-produced ceramides. Stable expression of a dominant-negative form of the FAN protein (factor associated with neutral sphingomyelinase activation), which has been reported to mediate tumor necrosis factor-induced activation of neutral sphingomyelinase, significantly inhibited CD40 ligand-induced sphingomyelinase stimulation and apoptosis of transformed human fibroblasts. Transformed fibroblasts from FAN knockout mice were also protected from CD40-mediated cell death. Finally, anti-CD40 antibodies were able to co-immunoprecipitate FAN in control fibroblasts but not in cells expressing the dominant-negative form of FAN, indicating interaction between CD40 and FAN. Altogether, these results strongly suggest that CD40 ligation can activate via FAN a neutral sphingomyelinase-mediated ceramide pathway that is involved in the cell growth inhibitory effects of CD40.
Kontrolliertes Einstellen der Säure/Base‐Oberflächeneigenschaften flammensynthetisierter Pt/Al<sub>2</sub>O<sub>3</sub>‐Katalysatoren (2010)

Es wurden stabile w/o-Mikroemulsionen aus wässriger Phase, Cyclohexan und verschiedenen Tensiden der Marlipal O13-Reihe erzeugt und darin via
Evidence for retinal remodelling in retinitis pigmentosa caused by PDE6B mutation (2007)

Retinitis pigmentosa is a genetically heterogeneous group of progressive retinal degenerations.1 Autosomal recessive retinitis pigmentosa caused by mutations in the gene encoding the β-subunit of rod photoreceptor cyclic guanosine monophosphate-phosphodiesterase (PDE6B) was one of the first forms to be identified, and there are well-studied murine and canine animal models as well as proof-of-concept success of somatic gene therapy.1–4 Rapid rod photoreceptor degeneration in the animal models is complicated by morphological changes involving the inner retina.5,6 It is unknown, however, whether the human form of retinitis pigmentosa is also complicated by retinal remodelling; the answer could have implications for treatment potential. We used optical coherence tomography (OCT) to study the retina of a patient with retinitis pigmentosa with a known PDE6B null mutation,7 and found there was abnormal laminar architecture suggesting retinal remodelling.

A 25-year-old woman with retinitis pigmentosa was homozygous for the Cys270X mutation in PDE6B . There was no rod function and only severely impaired cone function.7

At 34 years of age, …
Radiosensitization by Chir-124, a selective Chk1 inhibitor: Effects of p53 and cell cycle checkpoints (2009)

Checkpoint kinase-1 (CHK1) is a key regulator of the DNA damage-elicited G(2)-M checkpoints. The aim of the present study was to investigate the effects of a selective CHK1 inhibitor, Chir124, on cell survival and cell cycle progression following ionizing radiation (IR). Treatment with Chir-124 resulted in reduced clonogenic survival and abrogated the IR-induced G(2)-M arrest in a panel of isogenic HCT116 cell lines after IR. This radiosensitizing effect was relatively similar between p53(-/-) and p53-sufficient wild type (WT) HCT116 cells. However, the number of mitotic cells (as measured by assessing the phosphorylation of mitotic proteins) increased dramatically in p53(-/-) HCT116 cells after concomitant Chir-124 exposure, compared to IR alone, while no such effect was observed in p53-sufficient WT HCT116 cells. In p53(-/-) cells, Chir-124 treatment induced a marked accumulation of polyploid cells that were characterized by micronucleation or multinucleation. p21(-/-) HCT116 cells displayed a similar pattern of response as p53(-/-) cells. Chir-124 was able to radiosensitize HCT116 cells that lack checkpoint kinase-2 (CHK2) or that were deficient for the spindle checkpoint protein Mad2. Finally, Chir-124 could radiosensitize tetraploid cell lines, which were relatively resistant against DNA damaging agents. Altogether these results suggest that Chir-124-mediated radiosensitization is profoundly influenced by the p53 and cell cycle checkpoint system.
Flexible super-durable polyester based powder coatings (1999)

A new type of carboxyl terminated polyester resin, combining excellent flexibility with outstanding outdoor durability when used in pigmented powder coatings, has been developed. The resin can be cross-linked with either triglycidylisocyanurate (TGIC) or a hydroxyalkylamide type hardener and will be known as flexible super-durable polyester.
Fan-in and Fan-out with Optical Interconnections (1985)

Optical beams are known to have many desirable properties when used for providing interconnections. Such interconnections would be used in an all-optical computer based on optical gates, but can be used at various levels of architecture in electronic computing systems. The fan-out of optical interconnections from one computing element to N computing elements is accompanied by an N-fold loss of light power for each connection. Less obvious is the fact that fan-in of connections from N- computing elements to a single computing element can in some cases also be accompanied by an N -fold loss of power.
Grating-Slit: An Unusual Optical Surface Test (2006)

This method uses a DMD chip to generate a sinusoidal grating as the light source and uses a slit modulating light at the image location. The transverse ray aberration function is obtained through phase shifting.
Subjective comparison of music production practices using the Web Audio Evaluation Tool (2016)

The Web Audio Evaluation Tool is an open-source, browser-
based framework for creating and conducting listening tests.
It allows remote deployment, GUI-guided setup, and analy-
sis in the browser. While currently being used for listening
tests in various fields, it was initially developed specifically
for the study of music production practices. In this work,
we highlight some of the features that facilitate evaluation
of such content.
Synthesis and Characterizations of a Very Low Index Silica Aerogel Optical Thin Film (2022)

Very low index silica aerogel thin films were deposited by spin-coating silica sols synthesized by a two-step acid/base catalyzed method. The film shows an index as low as 1.117 and an optical absorption of 10 ppm.
High Temperature Data Retention of Ferroelectric Memory on 130nm and 180nm CMOS (2016)

Systematic evaluation of ferroelectric memory (FRAM) data retention mechanisms under high temperature exposure are reported. The FRAM devices are embedded on ultra-low power, analog-enhanced 130nm and 180nm CMOS technologies. Capability of the FRAM to retain data through 260°C Pb-free solder assembly reflow is demonstrated. The 130nm FRAM is shown to achieve the equivalent of 10 years data retention at 125°C, with intrinsic margin comparable to the 180nm FRAM, previously shown to achieve 10 years at 125°C retention.
Slide-ring materials: new polymeric materials for DDS (2006)

DDS用の新しい高分子材料である環動高分子材料について, 基礎的知見から最近の応用までを概説する. ポリロタキサンの環動特性を最もよく利用した環動高分子材料の一つである環動ゲルは, 滑車のように自由に動く架橋点を持つことから, 従来の化学ゲルとは力学特性が大きく異なり, むしろ生体に近い特性を示す. また, 中性子小角散乱の測定結果から, 環動ゲルでは滑車効果によりゲルの不均一構造が緩和することが明らかになった. さらに, 最近発見されたメチル化ポリロタキサンのゾル-ゲル転移について紹介し, 環動高分子材料のDDSへの応用と今後の展望を概観する.
Terahertz packaging: Study of substrates for novel component designs (2010)

This paper will examine a new side to packaging: Terahertz (THz) Packaging. The goal of this paper is three fold: 1) characterizing dielectric materials for THz packaging applications; 2) Using these materials in the fabrication of THz passives (integrated and quasi-optical); and 3) Demonstrating non-destructive evaluation of packages using THz. In this manuscript, detailed characteristics of dielectric packaging materials in the THz spectral region are presented along with the theory used for the characterization procedure. THz non destructive evaluation (NDE) of electronics packages is observed in the form of delamination thickness detection and moisture content studies. Using the materials characterized, a planar THz power splitter and a quasi-optical THz bandstop interference filter are demonstrated. Furthermore, the power splitter is used as a THz microfluidic sensor.
In Vitro Cyclic Electron Transport in Barley Thylakoids follows Two Independent Pathways (1996)

In vitro cyclic electron transport around PSI was studied in thylakoids isolated from barley (Hordeum vulgare L.). Redox poising was obtained by using anaerobic conditions, preillumination, and the addition of 3-(3,4-dichlorophenyl)-1,1-dimethylurea. Postillumination rates of P700+ re-reduction of 1 to 5 electrons s-1 were observed, depending on the conditions. The thylakoids supported two parallel paths of cyclic electron transport that were distinguishable by differences in antimycin sensitivity, saturation characteristics, and substrate specificity. The pathway most sensitive to antimycin was not saturated at ferredoxin concentrations up to 50 [mu]M, whereas the more insensitive pathway was saturated at 5 [mu]M ferredoxin. At the lower concentration of reduced ferredoxin, the antimycin-sensitive rate of P700+ re-reduction was lower than the antimycin-insensitive rate. The lower range of reduced ferredoxin concentrations are closer to in vivo conditions. Flavodoxin is shown to mediate cyclic electron transport. Flavodoxin was less efficient in mediating the antimycin-sensitive pathway but mediated the antimycin-insensitive pathway as efficiently as ferredoxin. Antibodies raised against ferredoxin:NADP+ oxidoreductase had no effect on either pathway for re-reduction of P700+. However, the ferredoxin: NADP+ oxidoreductase inhibitor 2[prime]-monophosphoadenosine-5[prime]-diphosphoribose was able to inhibit the antimycin-sensitive as well as the antimycin-insensitive pathway.
Cellular senescence and senescence‐associated secretory phenotype via the cGAS‐STING signaling pathway in cancer (2019)

Cellular senescence is historically regarded as a tumor suppression mechanism to prevent damaged cells from aberrant proliferation in benign and premalignant tumors. However, recent findings have suggested that senescent cells contribute to tumorigenesis and age-associated pathologies through the senescence-associated secretory phenotype (SASP). Therefore, to control age-associated cancer, it is important to understand the molecular mechanisms of the SASP in the cancer microenvironment. New findings have suggested that the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway, a critical indicator of innate immune response, triggers the SASP in response to accumulation of cytoplasmic DNA (cytoplasmic chromatin fragments, mtDNA and cDNA) in senescent cells. Notably, the cGAS-STING signaling pathway promotes or inhibits tumorigenesis depending on the biological context in vivo, indicating that it may be a potential therapeutic target for cancer. Herein, we review the regulatory machinery and biological function of the SASP via the cGAS-STING signaling pathway in cancer.
Identification of gaps in the clinical patient care of asthma in Spain. Results of the OPTIMA-GEMA survey (2016)

The priority areas for improvement were those related to asthma treatment. Future programs for implementation of asthma guidelines should prioritize the use of symptom questionnaires, nursing staff involvement, and attention to pregnant women with asthma.
Tdrd3 is a novel stress granule-associated protein interacting with the Fragile-X syndrome protein FMRP (2008)

Tudor domains are widespread among proteins involved in RNA metabolism, but only in a few cases their cellular function has been analyzed in detail. Here, we report on the characterization of the ubiquitously expressed Tudor domain containing protein Tdrd3. Apart from its Tudor domain, we show that Tdrd3 possesses an oligosaccharide/nucleotide binding fold (OB-fold) and an ubiquitin associated domain capable of binding tetra-ubiquitin. A set of biochemical experiments revealed an interaction of Tdrd3 with FMRP, the product of the gene affected in Fragile X syndrome, and its autosomal homologs FXR1 and FXR2. FMRP has been implicated in the translational regulation of target mRNAs and shown to be a component of stress granules (SG). We demonstrate that overexpression of Tdrd3 in cells induces the formation of SGs and as a result leads to its co-localization with endogenous FMRP in these structures. Interestingly, the disease-associated FMRP missense mutation I304N identified in a Fragile X patient severely impairs the interaction with Tdrd3 in biochemical experiments. We propose a contribution of Tdrd3 to FMRP-mediated translational repression and suggest that the loss of the FMRP-Tdrd3 interaction caused by the I304N mutation might contribute to the pathogenesis of Fragile X syndrome.