gebhart/patrepeval huggingface dataset:
Tyrosine Phosphorylation of I-κB Kinase α/β by Protein Kinase C-Dependent c-Src Activation Is Involved in TNF-α-Induced Cyclooxygenase-2 Expression (2003)

The signaling pathway involved in TNF-alpha-induced cyclooxygenase-2 (COX-2) expression was further studied in human NCI-H292 epithelial cells. A protein kinase C (PKC) inhibitor (staurosporine), tyrosine kinase inhibitors (genistein and herbimycin A), or a Src kinase inhibitor (PP2) attenuated TNF-alpha- or 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced COX-2 promoter activity. TNF-alpha- or TPA-induced I-kappaB kinase (IKK) activation was also blocked by these inhibitors, which reversed I-kappaBalpha degradation. Activation of c-Src and Lyn kinases, two Src family members, was inhibited by the PKC, tyrosine kinase, or Src kinase inhibitors. The dominant-negative c-Src (KM) mutant inhibited induction of COX-2 promoter activity by TNF-alpha or TPA. Overexpression of the constitutively active PKCalpha (PKCalpha A/E) or wild-type c-Src plasmids induced COX-2 promoter activity, and these effects were inhibited by the dominant-negative c-Src (KM), NF-kappaB-inducing kinase (NIK) (KA), or IKKbeta (KM) mutant. The dominant-negative PKCalpha (K/R) or c-Src (KM) mutant failed to block induction of COX-2 promoter activity caused by wild-type NIK overexpression. In coimmunoprecipitation experiments, IKKalpha/beta was found to be associated with c-Src and to be phosphorylated on its tyrosine residues after TNF-alpha or TPA treatment. Two tyrosine residues, Tyr(188) and Tyr(199), near the activation loop of IKKbeta, were identified to be crucial for NF-kappaB activation. Substitution of these residues with phenylalanines attenuated COX-2 promoter activity and c-Src-dependent phosphorylation of IKKbeta induced by TNF-alpha or TPA. These data suggest that, in addition to activating NIK, TNF-alpha also activates PKC-dependent c-Src. These two pathways cross-link between c-Src and NIK and converge at IKKalpha/beta, and go on to activate NF-kappaB, via serine phosphorylation and degradation of IkappaB-alpha, and, finally, to initiate COX-2 expression.
Caspases and cancer: mechanisms of inactivation and new treatment modalities. (2004)

Elimination of superfluous or mutated somatic cells is provided by various mechanisms including apoptosis. Deregulation of apoptotic signaling pathways may contribute to oncogenesis. Aspartate specific cysteine proteases, termed caspases are the key effector molecules in apoptosis. The aim of this review is to summarize the various defects in caspase-dependent cell death machinery identified in the neoplastic cells. These include not only mutations, but also alterations of gene methylation, and altered mRNA stability. Among the molecules that we discuss are elements of the extrinsic death pathway like CD95 (APO-1/Fas), FADD, FLIPs, FLICE, other apical caspases, components of the intrinsic apoptotic pathway like Apaf-1, caspase-9, and modulators of apoptotic pathways like IAPs, Smac/DIABLO, OMI/HtrA2, and other apoptosis regulating proteins. We also discuss recent data on cancer-specific agents that target effector mechanisms of apoptosis. Particular emphasis is given to the prospects for combining cell suicide-activating approaches with classical cancer therapies.
Triangular nanobeam photonic cavities in single-crystal diamond (2011)

Diamond photonics provides an attractive architecture to explore room temperature cavity quantum electrodynamics and to realize scalable multi-qubit computing. Here we review the present state of diamond photonic technology. The design, fabrication and characterization of a novel triangular cross section nanobeam cavity produced in a single crystal diamond is demonstrated. The present cavity design, based on a triangular cross section allows vertical confinement and better signal collection efficiency than that of slab-based nanocavities, and eliminates the need for a pre-existing membrane. The nanobeam is fabricated by Focused-Ion-Beam (FIB) patterning. The cavity is characterized by a confocal photoluminescence. The modes display quality factors of Q ~220 and are deviated in wavelength by only ~1.7nm from the NV- color center zero phonon line (ZPL). The measured results are found in good agreement with 3D Finite-Difference-Time-Domain (FDTD) calculations. A more advanced cavity design with Q=22,000 is modeled, showing the potential for high-Q implementations using the triangular cavity design. The prospects of this concept and its application to spin non-demolition measurement and quantum computing are discussed.
Efficient Combination of Recyclable Task Specific Ionic Liquid and Microwave Dielectric Heating for the Synthesis of Lipophilic Esters (2005)

Mild and efficient esterification reactions of carboxylic acids with neo-pentanol were carried out using task-specific ionic liquids with hydrogen sulphate counteranion under microwave irradiation. The latent acidity of the ionic liquid was introduced by anion metathesis from hydrogen sulphate with the corresponding imidazolium or pyridinium halides. The catalyst [C4mim][HSO4] modified with 5% of concentrated sulfuric acid was reused three times without considerable loss of activity in esterification using classical heating in oil bath.
Human Adipose-Derived Stem Cells as Future Tools in Tissue Regeneration: Osteogenic Differentiation and Cell-Scaffold Interaction (2008)

Tissue engineering is now contributing to new developments in several clinical fields, and mesenchymal stem cells derived from adipose tissue (hASCs) may provide a novel opportunity to replace, repair and promote the regeneration of diseased or damaged musculoskeletal tissue. Our interest was to characterize and differentiate hASCs isolated from twenty-three donors. Proliferation, CFU-F, cytofluorimetric and histochemistry analyses were performed. HASCs differentiate into osteogenic, chondrogenic, and adipogenic lineages, as assessed by tissue-specific markers such as alkaline phosphatase, osteopontin expression and deposition of calcium matrix, lipid-vacuoles formation and Glycosaminoglycans production. We also compared osteo-differentiated hASCs cultured on monolayer and loaded on biomaterials routinely used in the clinic, such as hydroxyapatite, cancellous human bone fragments, deproteinized bovine bone granules, and titanium. Scaffolds loaded with pre-differentiated hASCs do not affect cell proliferation and no cellular toxicity was observed. HASCs tightly adhere to scaffolds and differentiated-hASCs on human bone fragments and bovine bone granules produced, respectively, 3.4- and 2.1-fold more calcified matrix than osteo-differentiated hASCs on monolayer. Moreover, both human and deproteinized bovine bone is able to induce osteogenic differentiation of CTRL-hASCs. Although our in vitro results need to be confirmed in in vivo bone regeneration models, our data suggest that hASCs may be considered suitable biological tools for the screening of innovative scaffolds that would be useful in tissue engineering.
FoxM1 as a Novel Therapeutic Target for Cancer Drug Therapy (2015)

Current cancer therapy mainly focuses on identifying novel targets crucial for tumorigenesis. The FoxM1 is of preference as an anticancer target, due to its significance in execution of mitosis, cell cycle progression, as well as other signal pathways leading to tumorigenesis. FoxM1 is partially regulated by oncoproteins or tumor suppressors, which are often mutated, lost, or overexpressed in human cancer. Since sustaining proliferating signaling is an important hallmark of cancer, FoxM1 is overexpressed in a series of human malignancies. Alarge- scale gene expression analysis also identified FoxM1 as a differentially-expressed gene in most solid tumors. Furthermore, overexpressed FoxM1 is correlated with the prognosis of cancer patients, as verified in a series of malignancies by Cox regression analysis. Thus, extensive studies have been conducted to explore the roles of FoxM1 in tumorigenesis, making it an attractive target for anticancer therapy. Several antitumor drugs have been reported to target or inhibit FoxM1 expression in different cancers, and down-regulation of FoxM1 also abrogates drug resistance in some cancer cell lines, highlighting a promising future for FoxM1 application in the clinic.
CHOP is the standard regimen in patients > or = 70 years of age with intermediate-grade and high-grade non-Hodgkin's lymphoma: results of a randomized study of the European Organization for Research and Treatment of Cancer Lymphoma Cooperative Study Group. (1998)

CHOP is the standard regimen for patients > or = 70 years of age with stage II to IV intermediate- and high-grade NHL.
Mouth parts of the mustard aphid, Lipaphis erysimi Kalt. (1995)

The mouth parts of mustard aphid, Lipaphis erysimi Kalt. are piercing and sucking type with three modified maxillary and mandibular stylets. The rostrum is four segmented, apical segment is as wide as penultimate one but longer reflexed backwards and reaching up to the second pair of coxae in the adult, and third pair of coxae in early nymphal stage. Small needle like hypopharynx is continuous with the preoral cavity which is posteriorly connected with the food canal. Two grooved capillary stylets are present on either side of rostrum. Labium is short, cylindrical, flap like in appearance and covers the base of the abdomen. A pair of each protractor and retractor muscles are also present which are connected with the supporting arm of tentorium.
Nonvalvular atrial fibrillation associated with cardioembolic stroke: the role of hypertensive heart disease (1990)

Epidemiologists have not identified high risk groups nor the entire spectrum of heart disease, especially the subclinical forms underlying nonvalvular atrial fibrillation (NVAF) predisposing to cardioembolic (CE) stroke. We analysed 36 cases of 'isolated' NVAF among 106 consecutive cases of CE stroke after excluding cases of AF associated with valvular disease, myocardial infarcts, ischaemic and other cardio-myopathies (34 cases). This revealed echocardiographic left ventricular hypertrophy (LV mass index 136 +/- 25 g, vs normal 68 +/- 12 g p less than 0.001), enlarged left atria (left atrial area 27.4 +/- 3.6 cm2 vs normal 14.3+/- 1.6 cm2 p less than 0.001), normal systolic function and formed the largest group associated with CE stroke (34%), mean age 72.6 years--Study Group D. Eighty nine per cent had known or undetected hypertension compared to 60% in matched controls (x2 = 8.3 df = 1 p less than 0.01), and hypertension remained the predominant risk factor for left ventricular hypertrophy (LVH). Although all had echocardiographic LVH, 60% had neither electrocardiographic LVH nor cardiomegaly on chest X-ray. Hence usual epidemiologic methods may fail to detect these cases. Hypertensive heart disease is known to predispose to left atrial enlargement and AF. Progressive atrial enlargement is associated with increasing risk of embolic stroke. We conclude that NVAF associated with hypertensive heart disease forms a major component of the spectrum of heart disease associated with NVAF predisposing to CE stroke. Detection and treatment of hypertension to prevent or reverse LVH and atrial enlargement should be an important preventive measure.
Micromachined pre-focusedM×Nflow switches for continuous multi-sample injection (2001)

In this paper we present a novel microfluidic chip capable of continuous multi-sample switching and injection for bio-analytical applications. The innovative device integrates two important microfluidic phenomena, including hydrodynamic focusing and valveless flow switching inside multi-ported microchannels. The multiple samples can be pre-focused to narrow streams and can then be continuously injected into desired outlet ports. In this study, a theoretical model based on the `flow-rate-ratio' method is first proposed to predict the performance of the microfluidic device. Then, a simple but reliable one-mask micromachining process is developed to fabricate the pre-focused M×N flow switch on a quartz substrate. The multi-sample switching and injection is then verified experimentally with the use of microscopic visualization of water sheath flows and dye-containing sample flows. The experimental data indicate that the multi-sample flows can be hydrodynamically pre-focused and then guided into the desired outlet ports precisely based on relative sheath and sample flow rates. The data predicted by the proposed theoretical model are highly consistent with the experimental results. It is also noted that the `pre-focusing' function added prior to multi-sample flow switching is crucial for precise sample injection. The novel microfluidic chip has great potential for high-throughput chemical analysis, cell fusion, fraction collection, fast sample mixing and many other applications in the field of micro-total-analysis systems.
A Novel SCN9A Mutation Responsible for Primary Erythromelalgia and Is Resistant to the Treatment of Sodium Channel Blockers (2013)

Primary erythromelalgia (PE) is an autosomal dominant neurological disorder characterized by severe burning pain and erythema in the extremities upon heat stimuli or exercise. Mutations in human SCN9A gene, encoding the α-subunit of the voltage-gated sodium channel, Na(v)1.7, were found to be responsible for PE. Three missense mutations of SCN9A gene have recently been identified in Taiwanese patients including a familial (I136V) and two sporadic mutations (I848T, V1316A). V1316A is a novel mutation and has not been characterized yet. Topologically, I136V is located in DI/S1 segment and both I848T and V1316A are located in S4-S5 linker region of DII and DIII domains, respectively. To characterize the elelctrophysiological manifestations, the channel conductance with whole-cell patch clamp was recorded on the over-expressed Chinese hamster overy cells. As compared with wild type, the mutant channels showed a significant hyperpolarizing shift in voltage dependent activation and a depolarizing shift in steady-state fast inactivation. The recovery time from channel inactivation is faster in the mutant than in the wild type channels. Since warmth can trigger and exacerbate symptoms, we then examine the influence of tempearture on the sodium channel conduction. At 35°C, I136V and V1316A mutant channels exhibit a further hyperpolarizing shift at activation as compared with wild type channel, even though wild type channel also produced a significant hyperpolarizing shift compared to that of 25°C. High temperature caused a significant depolarizing shift in steady-state fast inactivation in all three mutant channels. These findings may confer to the hyperexcitability of sensory neurons, especially at high temperature. In order to identifying an effective treatment, we tested the IC₅₀ values of selective sodium channel blockers, lidocaine and mexiletine. The IC₅₀ for mexiletine is lower for I848T mutant channel as compared to that of the wild type and other two mutants which is comparable to the clinical observations.
Phenolic metabolites of clomiphene. [(E,Z)-2-[4-(1,2-diphenyl-2-chlorovinyl)phenoxy]ethyl]diethylamine. Preparation, electrophilicity, and effects in MCF 7 breast cancer cells (1989)

The triarylethylene antiestrogen clomiphene was previously shown to undergo biotransformation to an active metabolite, 4-hydroxyclomiphene, and to 3-methoxy-4-hydroxyclomiphene plus the respective regioisomers of these, 4 and 5. We now report the synthesis and further chemical and biochemical studies on 3-5. Coupling of 4-[2-(diethylamino)ethoxy]benzophenone with either 4-(benzyloxy)benzaldehyde or its 3-methoxy analogue 11b in the presence of titanium, followed by chlorination and deprotection of the intermediate triarylethylenes, gave 4 and 5, respectively. Condensation of benzylmagnesium chloride with the (2-methoxyethoxy)methyl (MEM) ether of 4-[2-(diethylamino)ethoxy]-3'-methoxy-4'-hydroxybenzophenone, followed by mild acid treatment, afforded deschloro 3 due to facile MEM ether hydrolysis. Acetylation of this, followed by chlorination and deacetylation, gave 3. Compounds 4 and 5 reacted readily with nucleophiles. In particular, 2-mercaptoethanol reacted with 4 to afford deschloro vinyl thioether 13 as suggested by NMR spectral studies, a result that implicated allene-quinone 14 as the electrophilic species produced in solution from 4. Antiestrogen binding sites and estrogen receptors from MCF 7 human breast cancer cells interacted with 3 and 5 with affinities comparable to those of tamoxifen and 1, respectively; 5 was shown not to bind irreversibly with these sites. Inhibition of MCF 7 cell proliferation by 3-5 at 5 microM concentrations (76%, 57%, and 49%, respectively, relative to drug-free controls) compared favorably to that observed with 5 microM 1 (80%). These results suggest that 3-5 as well as 2 may contribute to the antiestrogenic effects of 1.
Construction and biological activity of a full‐length molecular clone of human Torque teno virus (TTV) genotype 6 (2007)

Torque teno virus (TTV) is a non-enveloped human virus with a circular negative-sense (approximately 3800 nucleotides) ssDNA genome. TTV resembles in genome organization the chicken anemia virus, the animal pathogen of the Circoviridae family, and is currently classified as a member of a new, floating genus, Anellovirus. Molecular and cell biological research on TTV has been restricted by the lack of permissive cell lines and functional, replication-competent plasmid clones. In order to examine the key biological activities (i.e. RNA transcription and DNA replication) of this still poorly characterized ssDNA virus, we cloned the full-length genome of TTV genotype 6 and transfected it into cells of several types. TTV mRNA transcription was detected by RT-PCR in all the cell types: KU812Ep6, Cos-1, 293, 293T, Chang liver, Huh7 and UT7/Epo-S1. Replicating TTV DNA was detected in the latter five cell types by a DpnI-based restriction enzyme method coupled with Southern analysis, a novel approach to assess TTV DNA replication. The replicating full-length clone, the cell lines found to support TTV replication, and the methods presented here will facilitate the elucidation of the molecular biology and the life cycle of this recently identified human virus.
Influence of liposomal irinotecan (nal-IRI) and non-liposomal irinotecan, alone and in combination, on tumor growth and angiogenesis in colorectal cancer (CRC) models. (2018)

711 Background: The long circulating liposomal irinotecan nal-IRI (MM-398/PEP02, Onivyde) is approved for treatment of metastatic pancreatic cancer after disease progression with gemcitabine-based therapy. Besides their direct cytotoxic activity, camptothecins are thought to inhibit tumor angiogenesis via downregulating hypoxia-inducible factor 1 leading to attenuation of VEGF expression. Due to different deposition kinetics, irinotecan HCl and nal-IRI are likely to show different activities in vivo suggesting that a combination of the two agents may optimize intratumoral exposure and improve treatment efficacy. Methods: The activities of nal-IRI, irinotecan and their combination were compared in three human CRC xenograft models with different sensitivity to SN-38, the active metabolite of irinotecan, in vitro. Nal-IRI was dosed at 5 mg/kg q7d, while irinotecan HCl was dosed at 25 mg/kg at days 1 and 2 q7d. The activity of different regimens on tumor cell viability, hypoxia markers and the microvascular density was determined by quantitative biomarker analysis. Results: The relative antitumor activity of nal-IRI was most pronounced in tumor models with natural or acquired irinotecan resistance. Combinations of nal-IRI with irinotecan HCl was significantly better than irinotecan HCl alone in all tumor models although nal-IRI only provided 10% additional irinotecan. The antitumor activity of nal-IRI and Irintecan HCl in combination was accompanied by up to two times more tumor cell death and a marked 3-7 fold reduction of the microvessel density. Despite the strong antiangiogenic effect resulting in tumor hypoxia, the increase in HIF1α and, to lesser degree, HIF2α, was relatively modest and VEGF signal intensity remained at 85-115% of control values. Conclusions: Our results suggest that both irinotecan HCl and nal-IRI can counteract the hypoxia-mediated increase of HIF1α in vivo as previously reported in vitro. Furthermore, the combination of the two formulations demonstrated significant efficacy benefits. A combination of irinotecan HCl and nal-IRI merits further clinical investigation.
Screening for obstructive sleep apnea before surgery: why is it important? (2009)

The STOP questionnaire is short and can be easily incorporated into routine screening of general or surgical patients.
Human NELL1 Protein Augments Constructive Tissue Remodeling with Biologic Scaffolds (2013)

Biologic scaffolds composed of extracellular matrix (ECM) derived from decellularized tissues effectively reprogram key stages of the mammalian response to injury, altering the wound microenvironment from one that promotes scar tissue formation to one that stimulates constructive and functional tissue remodeling. In contrast, engineered scaffolds, composed of purified ECM components such as collagen, lack the complex ultrastructure and composition of intact ECM and may promote wound healing but lack factors that facilitate constructive and functional tissue remodeling. The objective of the present study was to test the hypothesis that addition of NELL1, a signaling protein that controls cell growth and differentiation, enhances the constructive tissue remodeling of a purified collagen scaffold. An abdominal wall defect model in the rat of 1.5-cm(2) partial thickness was used to compare the constructive remodeling of a bovine type I collagen scaffold to a biologic scaffold derived from small intestinal submucosa (SIS)-ECM with and without augmentation with 17 μg NELL1 protein. Samples were evaluated histologically at 14 days and 4 months. The contractile response of the defect site was also evaluated at 4 months. Addition of NELL1 protein improved the constructive remodeling of collagen scaffolds but not SIS-ECM scaffolds. Results showed an increase in the contractile force of the remodeled skeletal muscle and a fast:slow muscle composition similar to native tissue in the collagen-treated group. The already robust remodeling response to SIS-ECM was not enhanced by NELL1 at the dose tested. These findings suggest that NELL1 protein does contribute to the enhanced constructive remodeling of skeletal muscle.
Cytotoxin of Pasteurella haemolytica acting on bovine leukocytes (1982)

The toxicity of Pasteurella haemolytica culture supernatant for bovine and porcine cells was evaluated by 51Cr release. Sterile bacterial culture supernatant was toxic for bovine pulmonary lavage cells, peripheral blood lymphocytes and neutrophils, and cultured peripheral blood mononuclear cells, resulting in marked 51Cr release. Only slight release was induced from cultured Madin-Darby bovine kidney cells, porcine pulmonary lavage cells, peripheral blood mononuclear cells, lymphocytes, or neutrophils. No release was detected with primary bovine spleen cell cultures, bovine erythrocytes, or porcine erythrocytes. The demonstrated specificity of this cytotoxin for bovine leukocytic cells may be important in the pathogenesis of bovine pneumonic pasteurellosis.