gebhart/patrepeval huggingface dataset:
Autophagy and senescence in cancer-associated fibroblasts metabolically supports tumor growth and metastasis, via glycolysis and ketone production (2012)

Senescent fibroblasts are known to promote tumor growth. However, the exact mechanism remains largely unknown. An important clue comes from recent studies linking autophagy with the onset of senescence. Thus, autophagy and senescence may be part of the same physiological process, known as the autophagy-senescence transition (AST). To test this hypothesis, human fibroblasts immortalized with telomerase (hTERT-BJ1) were stably transfected with autophagy genes (BNIP3, CTSB or ATG16L1). Their overexpression was sufficient to induce a constitutive autophagic phenotype, with features of mitophagy, mitochondrial dysfunction and a shift toward aerobic glycolysis, resulting in L-lactate and ketone body production. Autophagic fibroblasts also showed features of senescence, with increased p21(WAF1/CIP1), a CDK inhibitor, cellular hypertrophy and increased β-galactosidase activity. Thus, we genetically validated the existence of the autophagy-senescence transition. Importantly, autophagic-senescent fibroblasts promoted tumor growth and metastasis, when co-injected with human breast cancer cells, independently of angiogenesis. Autophagic-senescent fibroblasts stimulated mitochondrial metabolism in adjacent cancer cells, when the two cell types were co-cultured, as visualized by MitoTracker staining. In particular, autophagic ATG16L1 fibroblasts, which produced large amounts of ketone bodies (3-hydroxy-butyrate), had the strongest effects and promoted metastasis by up to 11-fold. Conversely, expression of ATG16L1 in epithelial cancer cells inhibited tumor growth, indicating that the effects of autophagy are compartment-specific. Thus, autophagic-senescent fibroblasts metabolically promote tumor growth and metastasis, by paracrine production of high-energy mitochondrial fuels. Our current studies provide genetic support for the importance of "two-compartment tumor metabolism" in driving tumor growth and metastasis via a simple energy transfer mechanism. Finally, β-galactosidase, a known lysosomal enzyme and biomarker of senescence, was localized to the tumor stroma in human breast cancer tissues, providing in vivo support for our hypothesis. Bioinformatic analysis of genome-wide transcriptional profiles from tumor stroma, isolated from human breast cancers, also validated the onset of an autophagy-senescence transition. Taken together, these studies establish a new functional link between host aging, autophagy, the tumor microenvironment and cancer metabolism.
Optical design of a compact telescope for the next generation Earth observation system (2017)

High resolution earth observing systems need bigger and bigger telescopes. The design of such telescopes is a key element for the satellite design. In order to improve the imaging resolution with minimum impact on the satellite, a big step must be made to improve the compactness of the telescope. This paper describes the comparative study of several compact optical designs. This compactness increases drastically the sensitivity of the telescope. The optical designs, their sensitivity, their performances, the need to implement active optics are discussed.
MyoD binds to the guanine tetrad nucleic acid structure. (1992)

A high affinity interaction between a protein and the guanine tetrad nucleic acid structure is described. Recombinant MyoD, a transcription factor that can initiate myogenesis, specifically bound to helical structures formed by stacks of guanine residues in square planar arrays. The N-7 methylation of a set of consecutive dG residues in a single-stranded probe of the creatine kinase enhancer interfered with the formation of this nucleic acid structure and prevented protein binding. Recombinant MyoD also bound to a guanine tetrad formed with a telomeric DNA probe, and it had a higher affinity for the four-stranded structure than for the double-stranded E-box-binding site. These data are the first report of a direct interaction between a protein and this nucleic acid conformation. The potential biological significance of this finding is discussed.
Skew Estimation by Instances (2008)

This paper proposes a novel skew estimation method by instances. The instances to be learned (i.e., stored) are rotation invariants and a rotation variant for each character category. Using the instances, it is possible to estimate a skew angle of each individual character on a document. This fact implies that the proposed method can estimate the skew angle of a document where characters do not form long straight text lines. Thus, the proposed method will be applicable to various documents such as signboard images captured by a camera. Experimental evaluation using synthetic and real images revealed the expected robustness against various character layouts.
Biosynthesis of Red Tide Toxins (1990)

The biosynthesis of two major classes of red tide toxins, saxitoxin analogs and brevetoxins, have been studied. It was shown that saxitoxin is biosynthesized from arginine, acetate, and methionine methyl group. Brevetoxins were shown to be unique polyketides, which are probably biosynthesized from dicarboxylic acids. Some details of the biosynthetic mechanism have been elucidated.
Requirements for CD28-dependent T cell-mediated cytotoxicity (1993)

Small, resting human peripheral blood T cells are able to mediate anti-CD3 redirected lysis against murine P815 cells transfected with human B7, a ligand of CD28. We demonstrate that cytotoxicity is mediated by preexisting cytotoxic effectors within the small, resting "memory" T cell population and by the de novo generation of additional CTL within both the "memory" and "virgin" T subsets. This conclusion is based on analysis of the kinetics of the response and the effects of metabolic inhibitors on the generation of CTL function. Memory CD45RO+ T cells demonstrated cytotoxicity within 4 h of coculture with anti-CD3 mAb and B7+ P815 cells and cytolysis was only partially prevented by inhibitors of protein synthesis. By contrast, virgin CD45RO- T cells demonstrated anti-CD3-induced lysis against B7+ P815 targets only after 6 or 8 h of coculture and cytotoxicity was completely prevented by inhibiting protein synthesis. Induction of cytotoxicity was B7 dependent in that parental P815 cells and P815 cells transfected with CD72 and vascular cell adhesion molecule-1, ligands for T cell-associated membrane receptors CD5 and very late activation antigen-4, respectively, did not initiate cytotoxicity. Our studies also revealed cooperation between the CD28/B7 and lymphocyte function-associated Ag-1/intercellular adhesion molecule-1 pathways in the generation of CTL from small, resting T cells. However, after CTL generation, the CD28-B7 interaction was not required for cytotoxic effector cell function. These observations may have important physiologic implications because this would permit activated CTL to lyse targets in vivo that do not express B7, after the CTL were generated by APC that do express B7 or possibly other costimulatory molecules.
Identification and characterization of NleA, a non‐LEE‐encoded type III translocated virulence factor of enterohaemorrhagic Escherichia coli O157:H7 (2004)

Enterohaemorrhagic Escherichia coli (EHEC) O157:H7 uses a specialized protein translocation apparatus, the type III secretion system (TTSS), to deliver bacterial effector proteins into host cells. These effectors interfere with host cytoskeletal pathways and signalling cascades to facilitate bacterial survival and replication and promote disease. The genes encoding the TTSS and all known type III secreted effectors in EHEC are localized in a single pathogenicity island on the bacterial chromosome known as the locus for enterocyte effacement (LEE). In this study, we performed a proteomic analysis of proteins secreted by the LEE-encoded TTSS of EHEC. In addition to known LEE-encoded type III secreted proteins, such as EspA, EspB and Tir, a novel protein, NleA (non-LEE-encoded effector A), was identified. NleA is encoded in a prophage-associated pathogenicity island within the EHEC genome, distinct from the LEE. The LEE-encoded TTSS directs translocation of NleA into host cells, where it localizes to the Golgi apparatus. In a panel of strains examined by Southern blot and database analyses, nleA was found to be present in all other LEE-containing pathogens examined, including enteropathogenic E. coli and Citrobacter rodentium, and was absent from non-pathogenic strains of E. coli and non-LEE-containing pathogens. NleA was determined to play a key role in virulence of C. rodentium in a mouse infection model.
Adult olfactory epithelium contains multipotent progenitors that give rise to neurons and non-neural cells (1998)

We have infused replication-incompetent retroviral vectors into the nasal cavity of adult rats 1 day after exposure to the olfactotoxic gas methyl bromide (MeBr) to assess the lineage relationships of cells in the regenerating olfactory epithelium. The vast majority of the retrovirus-labeled clones fall into three broad categories: clones that invariably contain globose basal cells (GBCs) and/or neurons, clones that always include cells in the ducts of Bowman's glands, and clones that are composed of sustentacular cells only. Many of the GBC-related clones contain sustentacular cells and horizontal basal cells as well. Most of the duct-related clones contain gland cells, and some also include sustentacular cells. Thus, the destruction of both neurons and non-neuronal cells that is caused by MeBr activates two distinct types of multipotent cells. The multipotent progenitor that gives rise to neurons and non-neuronal cells is a basal cell, whereas the progenitor that gives rise to duct, gland, and sustentacular cells resides within the ducts, based on the pattern of sparing after lesion and the analysis of early regeneration by using cell type-specific markers. We conclude that the balance between multipotency and selective neuropotency, which is characteristic of globose basal cells in the normal olfactory epithelium, is determined by which cell types have been depleted and need to be replenished rapidly.
Increases in Bone Density During Treatment of Men with Idiopathic Hypogonadotropic Hypogonadism* (1989)

To assess the effects of gonadal steroid replacement on bone density in men with osteoporosis due to severe hypogonadism, we measured cortical bone density in the distal radius by 125I photon absorptiometry and trabecular bone density in the lumbar spine by quantitative computed tomography in 21 men with isolated GnRH deficiency while serum testosterone levels were maintained in the normal adult male range for 12-31 months (mean +/- SE, 23.7 +/- 1.1). In men who initially had fused epiphyses (n = 15), cortical bone density increased from 0.71 +/- 0.02 to 0.74 +/- 0.01 g/cm2 (P less than 0.01), while trabecular bone density did not change (116 +/- 9 compared with 119 +/- 7 mg/cm3). In men who initially had open epiphyses (n = 6), cortical bone density increased from 0.62 +/- 0.01 to 0.70 +/- 0.03 g/cm2 (P less than 0.01), while trabecular bone density increased from 96 +/- 13 to 109 +/- 12 mg/cm3 (P less than 0.01). Cortical bone density increased 0.03 +/- 0.01 g/cm2 in men with fused epiphyses and 0.08 +/- 0.02 g/cm2 in men with open epiphyses (P less than 0.05). Despite these increases, neither cortical nor trabecular bone density returned to normal levels. Histomorphometric analyses of iliac crest bone biopsies demonstrated that most of the men had low turnover osteoporosis, although some men had normal to high turnover osteoporosis. We conclude that bone density increases during gonadal steroid replacement of GnRH-deficient men, particularly in men who are skeletally immature.
Follicle-Stimulating Hormone and lntracellular Second Messengers Regulate Steroidogenic Acute Regulatory Protein Messenger Ribonucleic Acid in Luteinized Porcine Granulosa Cells1 (1997)

Ligand- and second messenger-regulated expression of the gene for steroidogenic acute regulatory protein (StAR) was evaluated in luteinized porcine granulosa cells. For comparison, cytochrome P450 side-chain cleavage (P450scc) was examined. Northern hybridization with homologous cDNA probes demonstrated three StAR mRNA species, of 2.7, 1.6, and 0.8 kilobases (kb), with the smallest variably present, and a single P450scc band at 1.9 kb. FSH elevated both STAR and P450scc messages in a dose-dependent manner over 6 h and continually stimulated both over 24 h (p < 0.001). STAR message induction depended on transcription, as did that of P450scc. Over 6 h, actinomycin D eliminated constitutive StAR message and reduced that of P450scc by two thirds, indicating briefer persistence of StAR. Pretreatment with cycloheximide prevented FSH induction of StAR and P450scc mRNA, implicating intermediate protein synthesis in expression of both genes. Dibutyryl cAMP caused time-dependent increases in StAR and P450 mRNAs over 24 h (p < 0.001), indicating the importance of the protein kinase A (PKA) pathway in their gene expression. Activation of the protein kinase C (PKC) pathway by a phorbol ester eliminated FSH induction of STAR mRNA increases (p < 0.01) while only reducing P450scc induction (p < 0.05). Thus, StAR gene expression, as reflected in mRNA abundance, is regulated by FSH via the PKA pathway and is dependent on transcription and translation. Conversely, the PKC pathway inhibits induction of these important steroid synthetic genes in luteinized granulosa cells.
Intratumoral regulatory T cells upregulate immunosuppressive molecules in head and neck cancer patients (2013)

These results indicate that intratumoral Treg are more immunosuppressive than circulating Treg and CTLA-4 and CD39 expressed can be potential target molecules to inhibit suppressive activities of intratumoral Treg in situ.
Trap-limited recombination in dye-sensitized nanocrystalline metal oxide electrodes (2001)

We use transient and steady-state optical spectroscopies to study the recombination reaction between electrons and dye cations in a dye-sensitized nanocrystalline ${\mathrm{TiO}}_{2}$ electrode in several different chemical environments. Kinetic decay curves are approximately stretched exponential, and the cation half-life, ${t}_{50%}$ varies with electron density n as ${t}_{50%}\ensuremath{\propto}{n}^{\ensuremath{-}1/\ensuremath{\alpha}},$ where \ensuremath{\alpha} is a constant in the range 0.2--0.5. We have developed a model of electron transport in the presence of an energetic distribution of trap states and consider two regimes. In the first, the continuous-time random-walk (CTRW) electrons are free to diffuse through the lattice, by means of multiple trapping events mediated by the conduction band. In the second, the hopping regime, trapped electrons are allowed to tunnel to other, vacant trap sites, or to the dye cation, according to a Miller-Abrahams model for the transition rate. We carry out Monte Carlo simulations of the recombination kinetics as a function of electron density, trap state distributions and other parameters. The CTRW reproduces both the dependence of ${t}_{50%}$ on n and the shape of the kinetic curves with only one free fitting parameter, for the case of an exponential density of trap states. The hopping model is ruled out by subnanosecond measurements. We conclude that multiple trapping with a broad energetic distribution of electron traps is responsible for the slow recombination kinetics. When applied to recombination in a nanocrystalline photovoltaic junction at open circuit, the model predicts a sublinear power-law variation of electron density with light intensity G, $n\ensuremath{\propto}{G}^{\ensuremath{\alpha}},$ compatible with the observed behavior.
Hydrogen bonds as design elements in organic chemistry (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHydrogen bonds as design elements in organic chemistryMargaret C. EtterCite this: J. Phys. Chem. 1991, 95, 12, 4601–4610Publication Date (Print):June 1, 1991Publication History Published online1 May 2002Published inissue 1 June 1991https://pubs.acs.org/doi/10.1021/j100165a007https://doi.org/10.1021/j100165a007research-articleACS PublicationsRequest reuse permissionsArticle Views3758Altmetric-Citations921LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options Get e-Alerts
Amyotrophic Lateral Sclerosis (ALS) treated with Low Level LASER Therapy (LLLT): a case report (2009)

The topic concerns the effect of LLLT on ALS. The purpose is to find a new and effective approach to treat ALS by utilizing the beneficial biological effects on human tissues provided by LLLT and by testing the effectiveness of a specific treatment protocol. There are no reports in literature dealing with this topic. A 69 year old male with signs of lower motor neuron degeneration diagnosed in 2003 as ALS was given LLLT. Two different types of LASERs (wavelengths 810 and 890 nm) where used with specific parameters in March 2007. Three cycles of 20 daily sessions at 40 days interval were given. Gradual and significant improvements were noted after each cycle particularly appreciated by the patient especially in muscular mobility and respiratory functions. However signs of improvement 20 days after the third cycle showed a tendency to regression. Results obtained indicate that LLLT with the specific protocol used gives significant improvement of the ALS clinical picture but that its duration is not permanent. Further research on a large cohort is justified especially as regards LASER parameters and treatment cycles.
Development of Novel In Vivo Chemical Probes to Address CNS Protein Kinase Involvement in Synaptic Dysfunction (2013)

Serine-threonine protein kinases are critical to CNS function, yet there is a dearth of highly selective, CNS-active kinase inhibitors for in vivo investigations. Further, prevailing assumptions raise concerns about whether single kinase inhibitors can show in vivo efficacy for CNS pathologies, and debates over viable approaches to the development of safe and efficacious kinase inhibitors are unsettled. It is critical, therefore, that these scientific challenges be addressed in order to test hypotheses about protein kinases in neuropathology progression and the potential for in vivo modulation of their catalytic activity. Identification of molecular targets whose in vivo modulation can attenuate synaptic dysfunction would provide a foundation for future disease-modifying therapeutic development as well as insight into cellular mechanisms. Clinical and preclinical studies suggest a critical link between synaptic dysfunction in neurodegenerative disorders and the activation of p38αMAPK mediated signaling cascades. Activation in both neurons and glia also offers the unusual potential to generate enhanced responses through targeting a single kinase in two distinct cell types involved in pathology progression. However, target validation has been limited by lack of highly selective inhibitors amenable to in vivo use in the CNS. Therefore, we employed high-resolution co-crystallography and pharmacoinformatics to design and develop a novel synthetic, active site targeted, CNS-active, p38αMAPK inhibitor (MW108). Selectivity was demonstrated by large-scale kinome screens, functional GPCR agonist and antagonist analyses of off-target potential, and evaluation of cellular target engagement. In vitro and in vivo assays demonstrated that MW108 ameliorates beta-amyloid induced synaptic and cognitive dysfunction. A serendipitous discovery during co-crystallographic analyses revised prevailing models about active site targeting of inhibitors, providing insights that will facilitate future kinase inhibitor design. Overall, our studies deliver highly selective in vivo probes appropriate for CNS investigations and demonstrate that modulation of p38αMAPK activity can attenuate synaptic dysfunction.
Infection of the amniotic cavity with Ureaplasma urealyticum in the midtrimester of pregnancy. (1995)

The purpose of this study was to determine the clinical significance of invasion of the amniotic fluid (AF) with Ureaplasma urealyticum in the midtrimester of pregnancy. Amniotic fluid and cervical swabs obtained from 214 asymptomatic women in the midtrimester of pregnancy (16-20 weeks) were cultured for U urealyticum and Mycoplasma hominis. Inoculum size was determined by quantitative culture. Six of the 214 women (2.8%) had Ureaplasma in high titers in the AF. The pregnancy outcomes of 129 women were determined. Adverse pregnancy outcome occurred more frequently in women with a positive AF culture than in women with a negative AF culture (3/6 [50%] vs. 15/123 [12%], respectively; P = .035). We conclude that infection of the amniotic cavity with U urealyticum can be present in asymptomatic patients in the midtrimester of pregnancy and is a significant risk factor for spontaneous preterm labor and delivery. These observations suggest that routine culture of AF at the time of midtrimester amniocentesis can identify the group of patients at risk for a poor pregnancy outcome.
Mantle Cell Lymphoma: A Clinically Heterogeneous Disease in Need of Tailored Approaches (2012)

Although patients with MCL continue to experience poor outcomes, new treatment approaches for various stages of disease are showing promise in improving survival.
Occupational asthma from nickel sensitivity: II. Factors influencing the interaction of Ni2+, HSA, and serum antibodies with nickel related specificity. (1984)

Serum from an individual with occupational asthma from nickel sulphate inhalation was shown by ammonium sulphate (Farr) and anti-IgG coprecipitation tests to contain antibodies which bind 63Ni2+. This binding was absent from 30 control sera. Ligand competition studies with serum and plasma from the propositus and controls are described, and include serial additions of HSA, L-histidine, EDTA, and the tripeptide gly-gly-L-his. The results, like those from metal ion blocking experiments, clearly showed that the formation of the reactive antigenic determinant depends on the selective binding of Ni2+ at the native Cu2+/Ni2+ transport site of HSA. Corroborating evidence is derived from the similar dependence on pH of the Ni2+-HSA formation and the ammonium sulphate 63Ni2+ coprecipitation reactions.
Video on Demand: Architecture, Systems, and Applications (1993)

This article describes video on demand (VOD) and near video on demand (NVOD) and explains the differences between the various types of VOD systems as they relate to telephone company (Telco), commmunity antenna or cable television (CATV), cellular TV, and hotel applications. System similarities of the various carriers are described, with the intent to identify as much common equipment as possible that will be compatible across the various applications. Basic VOD functional requirements are also discussed. Hotel VOD systems are really small CATV or Telco systems that can be expanded into full-size, commercially viable VOD systems easily because of their scalable architecture. The roles of image compression, video-friendly disk-storage systems, video servers, encryption, switching, transmission, and control-system elements in this VOD application are also discussed.