gebhart/patrepeval huggingface dataset:
Pluripotency can be rapidly and efficiently induced in human amniotic fluid-derived cells (2009)

Direct reprogramming of human somatic cells into pluripotency has broad implications in generating patient-specific induced pluripotent stem (iPS) cells for disease modeling and cellular replacement therapies. However, the low efficiency and safety issues associated with generation of human iPS cells have limited their usage in clinical settings. Cell types can significantly influence reprogramming efficiency and kinetics. To date, human iPS cells have been obtained only from a few cell types. Here, we report for the first time rapid and efficient generation of iPS cells from human amniotic fluid-derived cells (hAFDCs) via ectopic expression of four human factors: OCT4/SOX2/KLF4/C-MYC. Significantly, typical single iPS cell colonies can be picked up 6 days after viral infection with high efficiency. Eight iPS cell lines have been derived. They can be continuously propagated in vitro and express pluripotency markers such as AKP, OCT4, SOX2, SSEA4, TRA-1-60 and TRA-1-81, maintaining the normal karyotype. Transgenes are completely inactivated and the endogenous OCT4 promoter is adequately demethylated in the established iPS cell lines. Moreover, various cells and tissues from all three germ layers are found in embryoid bodies and teratomas, respectively. In addition, microarray analysis demonstrates a high correlation coefficient between hAFDC-iPS cells and human embryonic stem cells, but a low correlation coefficient between hAFDCs and hAFDC-iPS cells. Taken together, these data identify an ideal human somatic cell resource for rapid and efficient generation of iPS cells, allowing us to establish human iPS cells using more advanced approaches and possibly to establish disease- or patient-specific iPS cells.
Endocan Is Upregulated on Tumor Vessels in Invasive Bladder Cancer Where It Mediates VEGF-A–Induced Angiogenesis (2012)

Tumor-associated blood vessels differ from normal vessels and proteins present only on tumor vessels may serve as biomarkers or targets for antiangiogenic therapy in cancer. Comparing the transcriptional profiles of blood vascular endothelium from human invasive bladder cancer with normal bladder tissue, we found that the endothelial cell-specific molecule endocan (ESM1) was highly elevated on tumor vessels. Endocan was associated with filopodia of angiogenic endothelial tip cells in invasive bladder cancer. Notably, endocan expression on tumor vessels correlated strongly with staging and invasiveness, predicting a shorter recurrence-free survival time in noninvasive bladder cancers. Both endocan and VEGF-A levels were higher in plasma of patients with invasive bladder cancer than healthy individuals. Mechanistic investigations in cultured blood vascular endothelial cells or transgenic mice revealed that endocan expression was stimulated by VEGF-A through the phosphorylation and activation of VEGFR-2, which was required to promote cell migration and tube formation by VEGF-A. Taken together, our findings suggest that disrupting endocan interaction with VEGFR-2 or VEGF-A could offer a novel rational strategy to inhibit tumor angiogenesis. Furthermore, they suggest that endocan might serve as a useful biomarker to monitor disease progression and the efficacy of VEGF-A-targeting therapies in patients with bladder cancer.
Synthesis of optically active nicotinoids (1982)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of optically active nicotinoidsCharles G. Chavdarian, Edward B. Sanders, and Ronald L. BassfieldCite this: J. Org. Chem. 1982, 47, 6, 1069–1073Publication Date (Print):March 1, 1982Publication History Published online1 May 2002Published inissue 1 March 1982https://doi.org/10.1021/jo00345a034Request reuse permissionsArticle Views308Altmetric-Citations29LEARN 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 InReddit PDF (702 KB) Get e-Alertsclose Get e-Alerts
Human keratinocyte growth factor activity on proliferation and differentiation of human keratinocytes: Differentiation response distinguishes KGF from EGF family (1990)

Human keratinocyte growth factor (KGF) is an epithelial cell specific mitogen which is secreted by normal stromal fibroblasts. In the present studies, we demonstrate that KGF is as potent as EGF in stimulating proliferation of primary or secondary human keratinocytes in tissue culture. Exposure of KGF- or EGF-stimulated keratinocytes to 1.0 mM calcium, an inducer of differentiation, led to cessation of cell growth. However, immunologic analysis of early and late markers of terminal differentiation, K1 and filaggrin, respectively, revealed striking differences in keratinocytes propagated in the presence of these growth factors. With KGF, the differentiation response was associated with expression of both markers whereas their appearance was retarded or blocked by EGF. TGF alpha, which also interacts with the EGF receptor, gave a similar response to that observed with EGF. These findings functionally distinguish KGF from the EGF family and support the role of KGF in the normal proliferation and differentiation of human epithelial cells.
Use of the DNA sequence of variable regions of the 16S rRNA gene for rapid and accurate identification of bacteria in theLactobacillus acidophiluscomplex (2000)

The Lactobacillus acidophilus complex includes Lact. acidophilus, Lactobacillus amylovorus, Lactobacillus crispatus, Lactobacillus gallinarum, Lactobacillus gasseri and Lactobacillus johnsonii. The objective of this work was to develop a rapid and definitive DNA sequence-based identification system for unknown isolates of the Lact. acidophilus complex. A approximately = 500 bp region of the 16S rRNA gene, which contained the V1 and V2 variable regions, was amplified from the isolates by the polymerase chain reaction. The sequence of this region of the 16S rRNA gene from the type strains of the Lact. acidophilus complex was sufficiently variable to allow for clear differentiation amongst each of the strains. As an initial step in the characterization of potentially probiotic strains, this technique was successfully used to identify a variety of unknown human intestinal isolates. The approach described here represents a rapid and definitive method for the identification of Lact. acidophilus complex members.
Approaching Theoretical Capacity of LiFePO[sub 4] at Room Temperature at High Rates (2001)

Nanocomposites of and conductive carbon were prepared by two different methods which lead to enhanced electrochemical accessibility of the Fe redox centers in this insulating material. Method A employs a composite of the phosphate with a carbon xerogel formed from a resorcinol-formaldehyde precursor; method B uses surface-oxidized carbon particles to act as a nucleating agent for phosphate growth. Both particle size minimization and intimate carbon contact are necessary to optimize electrochemical performance. Although both methods succeed for the first criteria, the latter is best achieved with method A, affording excellent characteristics in room temperature, liquid electrolyte cells. The resultant composite achieves 90% theoretical capacity at C/2, with very good rate capability and excellent stability. © 2001 The Electrochemical Society. All rights reserved.
Two oncogenes, v-fos and v-ras, cooperate to convert normal keratinocytes to squamous cell carcinoma. (1990)

Previous studies have implicated the rasHa oncogene in the initiation of skin carcinogenesis and the fos oncogene in malignant progression of premalignant skin cell lines. To determine if these two oncogenes are sufficient to convert normal keratinocytes to cancer cells, freshly isolated mouse keratinocytes were coinfected with replication-defective (psi-2) v-rasHa and v-fos viruses in culture. When tested in nude mice within several days of infection, v-fos/v-rasHa-coinfected keratinocytes produced squamous cell carcinomas. Introduction of v-fos alone resulted in normal or hyperplastic skin, whereas v-rasHa alone produced squamous papillomas. These results indicate that two oncogenes are sufficient to produce the malignant phenotype in epidermal cells. Furthermore, they clearly link the fos oncogene with malignant conversion. Since fos acts as a transcriptional regulator of other genes, malignant conversion may be an indirect consequence of the overexpression of the fos-encoded protein leading to a change in the expression of fos-controlled cellular genes.
Locus control regions (2002)

Locus control regions (LCRs) are operationally defined by their ability to enhance the expression of linked genes to physiological levels in a tissue-specific and copy number-dependent manner at ectopic chromatin sites. Although their composition and locations relative to their cognate genes are different, LCRs have been described in a broad spectrum of mammalian gene systems, suggesting that they play an important role in the control of eukaryotic gene expression. The discovery of the LCR in the beta-globin locus and the characterization of LCRs in other loci reinforces the concept that developmental and cell lineage-specific regulation of gene expression relies not on gene-proximal elements such as promoters, enhancers, and silencers exclusively, but also on long-range interactions of various cis regulatory elements and dynamic chromatin alterations.
Nanotechnologies for Conservation of Cultural Heritage:  Paper and Canvas Deacidification (2002)

The aging of cellulose, the main constituent of paper, is due to depolymerization of cellulose fibers and is promoted by acid pH. Paper deacidification is a fundamental process for the conservation and restoration of probably the most important material used to transmit cultural heritage. Several methods are currently used for paper deacidification. We applied nanotechnologies to produce kinetically stable dispersions of nano- and micron-sized calcium hydroxide particles in alcohol media. Although calcium hydroxide possesses the best deacidification properties, it has never been used so far as dispersion in nonaqueous media. Calcium hydroxide particles, once deposited onto paper cellulose fibers, deacidify them and react with carbon dioxide from the air, forming a calcium carbonate reservoir on the paper fibers. This process allows a long-term control of paper pH, with excellent deacidification properties. Deacidification of 14th, 17th, 19th, and 20th century acid yellowed paper samples coming from rag and wood pulp (20th century) has been performed with excellent results. Moreover, the nano- and microparticle dispersions can be applied to paper or canvases using conventional procedures. This new method is environmentally clean, is inexpensive, and can also be used for industrial applications.
Novel Flexible Transparent Conductive Films with Enhanced Chemical and Electromechanical Sustainability: TiO2 Nanosheet–Ag Nanowire Hybrid (2017)

Flexible transparent conductive films (TCFs) of TiO<sub>2</sub> nanosheet (TiO<sub>2</sub> NS) and silver nanowire (Ag NW) network hybrid were prepared through a simple and scalable solution-based process. The as-formed TiO<sub>2</sub> NS-Ag NW hybrid TCF shows a high optical transmittance (TT: 97% (90.2% including plastic substrate)) and low sheet resistance (R<sub>s</sub>: 40 Ω/sq). In addition, the TiO<sub>2</sub> NS-Ag NW hybrid TCF exhibits a long-time chemical/aging and electromechanical stability. As for the chemical/aging stability, the hybrid TCF of Ag NW and TiO<sub>2</sub> NS reveals a retained initial conductivity (ΔR<sub>s</sub>/R<sub>s</sub> < 1%) under ambient oxidant gas over a month, superior to that of bare Ag NW (ΔR<sub>s</sub>/R<sub>s</sub> > 4000%) or RuO<sub>2</sub> NS-Ag NW hybrid (ΔR<sub>s</sub>/R<sub>s</sub> > 200%). As corroborated by the density functional theory simulation, the superb chemical stability of TiO<sub>2</sub> NS-Ag NW hybrid is attributable to the unique role of TiO<sub>2</sub> NS as a barrier, which prevents Ag NW's chemical corrosion via the attenuated adsorption of sulfidation molecules (H<sub>2</sub>S) on TiO<sub>2</sub> NS. With respect to the electromechanical stability, in contrast to Ag NWs (ΔR/R<sub>0</sub> ∼ 152.9%), our hybrid TCF shows a limited increment of fractional resistivity (ΔR/R<sub>0</sub> ∼ 14.4%) after 200 000 cycles of the 1R bending test (strain: 6.7%) owing to mechanically welded Ag NW networks by TiO<sub>2</sub> NS. Overall, our unique hybrid of TiO<sub>2</sub> NS and Ag NW exhibits excellent electrical/optical properties and reliable chemical/electromechanical stabilities.
Chronology and Determinants of Tissue Repair in Diabetic Lower-Extremity Ulcers (1991)

The natural history of tissue repair and the critical determinants of faulty healing of diabetic ulcers remain obscure despite recent advances in our knowledge of the cellular physiology of normal cutaneous healing. To characterize the chronology and identify important factors affecting healing, we applied an objective method to quantify the rate of wound healing of full-thickness lower-extremity ulcers in 46 diabetic outpatients who received local wound care under a standardized clinical protocol. The initial ulcer healing rate, eventual status of tissue repair, and definitive clinical outcome were not significantly associated with age; diabetes type, duration, or treatment; level or change in glycosylated hemoglobin; current smoking; presence of sensory neuropathy; ulcer location or class; initial infection; or frequency of recurrent infections. However, direct measures of local cutaneous perfusion, estimated by periwound measurements of transcutaneous O2 tension (TcPo2) and transcutaneous CO2 tension (TcPco2), were significantly associated with the initial rate of tissue repair (P = 0.003 and 0.005, respectively). The strong prediction of early healing by these parameters of local skin perfusion was independent from the effects of segmental Doppler arterial blood pressure at the dorsalis pedis, although eventual ulcer reepithelialization was significantly related to foot blood pressure and periwound TcPo2 and TcPco2. We conclude that periwound cutaneous perfusion is the critical physiological determinant of diabetic ulcer healing, indicating a 39-fold increased risk of early healing failure when the average periwound TcPo2 is less than 20 mmHg.
IMQ‐induced skin inflammation in mice is dependent on IL‐1R1 and MyD88 signaling but independent of the NLRP3 inflammasome (2015)

The pathogenesis of inflammatory skin diseases such as psoriasis involves the release of numerous proinflammatory cytokines, including members of the IL-1 family. Here we report overexpression of IL-1α, IL-1β, and IL-1 receptor antagonist mRNA, associated to expression of IL-23p19, IL-17A, and IL-22 in skin cells, upon topical application of the TLR7 agonist imiquimod (IMQ) in C57BL/6J mice. IMQ-induced skin inflammation was partially reduced in mice deficient for both IL-1α/IL-1β or for IL-1 receptor type 1 (IL-1R1), but not in IL-1α- or IL-1β-deficient mice, demonstrating the redundant activity of IL-1α and IL-1β for skin inflammation. NLRP3 or apoptosis-associated Speck-like protein containing a Caspase recruitment domain-deficient mice had no significant reduction of skin inflammation in response to IMQ treatment, mainly due to the redundancy of IL-1α. However, IMQ-induced skin inflammation was abolished in the absence of MyD88, the adaptor protein shared by IL-1R and TLR signaling pathways. These results are consistent with the TLR7 dependence of IMQ-induced skin inflammation. Thus, IL-1R1 contributes to the IMQ-induced skin inflammation, and disruption of MyD88 signaling completely abrogates this response.
The Rate of Bone Mineral Loss in Normal Men and the Effects of Calcium and Cholecalciferol Supplementation (1990)

Normal men experience a substantial bone loss at both axial and appendicular sites that is not prevented by calcium and vitamin D supplementation in a well-nourished population.
Azathioprine Metabolism: Pharmacokinetics of 6‐Mercaptopurine, 6‐Thiouric Acid and 6‐Thioguanine Nucleotides in Renal Transplant Patients (1990)

Despite extensive clinical experience with azathioprine (AZA), the disposition of various AZA metabolites remains obscure. We therefore evaluated the pharmacokinetics of three AZA metabolites: 6-mercaptopurine (6-MP), the immediate metabolite; 6-thiouric acid (6-TU), the final end product; and 6-thioguanine nucleotides (TGN), the active moiety; in eight renal transplant patients after oral administration of AZA. The low peak plasma 6-MP level of 73.7 +/- 23.7 ng/mL (mean +/- SD) and the short half-life (t1/2) of 1.9 +/- 0.6 hours suggest rapid conversion of 6-MP to other metabolites. A peak plasma 6-TU concentration of 1210 +/- 785 ng/mL was observed at 3.5 +/- 0.6 hours after the AZA dose. The strong correlation between 6-TU t1/2 and serum creatinine (r = 0.98, P = .0008) supported our previous work showing that 6-TU is primarily excreted by the kidneys. The total TGN levels in red blood cells (RBCs) in each patient remained largely unchanged over 24 hours with the intraindividual coefficient of variation ranging from 4.4% to 29.8%. In comparison, the mean TGN level varied considerably between patients, and ranged from undetectable to 413 pmol per 8 X 10(8) RBCs. However, there was no apparent correlation between white cell counts on day 0 (P greater than .5), day 7 (P greater than .5), or day 14 (P greater than .5) and RBC TGN level. The persistence of TGN in body tissues thus provides a pharmacokinetic rationale for the conventional once or twice daily AZA regimen.(ABSTRACT TRUNCATED AT 250 WORDS)
Automated statistical analysis of microbial enumeration by dilution series (1983)

Equations are formulated for the standard error and confidence interval for the MPN estimate of microbial density from a general dilution series. A statistical test of homogeneity is presented. This tests whether a handling error in the dilution series may have occurred which would invalidate the density estimate. The analysis may be automated using a Basic computer program which contains a fast algorithm for the solution of the general MPN equation. This allows the calculation of the MPN, standard error, 95% confidence interval and test statistic for any dilution series, with any degree of replication at each dilution level, with variable sample volumes at each dilution level, with variable dilution ratio between levels, and with any number of levels.
Inhibitors of protein synthesis and RNA synthesis prevent neuronal death caused by nerve growth factor deprivation. (1988)

We have developed an experimental paradigm to study the mechanism by which nerve growth factor (NGF) allows the survival of sympathetic neurons. Dissociated sympathetic neurons from embryonic day-21 rats were grown in vitro for 7 d in the presence of NGF. Neurons were then deprived of trophic support by adding anti-NGF antiserum, causing them to die between 24 and 48 h later. Ultrastructural changes included disruption of neurites, followed by cell body changes characterized by an accumulation of lipid droplets, changes in the nuclear membrane, and dilation of the rough endoplasmic reticulum. No primary alterations of mitochondria or lysosomes were observed. The death of NGF-deprived neurons was characterized biochemically by assessing [35S]methionine incorporation into TCA precipitable protein and by measuring the release of the cytosolic enzyme adenylate kinase into the culture medium. Methionine incorporation began to decrease approximately 18 h post-deprivation and was maximally depressed by 36 h. Adenylate kinase began to appear in the culture medium approximately 30 h after deprivation, reaching a maximum by 54 h. The death of NGF-deprived neurons was entirely prevented by inhibiting protein or RNA synthesis. Cycloheximide, puromycin, anisomycin, actinomycin-D, and dichlorobenzimidazole riboside all prevented neuronal death subsequent to NGF deprivation as assessed by the above morphologic and biochemical criteria. The fact that sympathetic neurons must synthesize protein and RNA to die when deprived of NGF indicates that NGF, and presumably other neurotrophic factors, maintains neuronal survival by suppressing an endogenous, active death program.
&lt;italic&gt;Conus&lt;/italic&gt; Peptides&mdash;A Rich Pharmaceutical Treasure (2004)

Marine predatory cone snails (genus Conus) with over 500 species represent what is arguably the largest single genus of marine animals alive today. All Conus are venomous and utilize a complex mixture of Conus peptides to capture their preys and for other biological purposes. Each component of Conus peptides selectively targets a specific subtype of ion channels, neurotransmitter receptors or transporters. Owing to their diversity, more than 50,000 distinct active peptides are theoretically estimated in Conus venoms. These diversified toxins are generally categorized into several superfamilies and/or families based on their characteristic arrangements of cysteine residues and pharmacological actions. Some mechanisms underlying the remarkable diversity of Conus peptides have been postulated: the distinctive gene structure, gene duplication and/or allelic selection, genus speciation, and sophisticated expression pattern and post-translational modification of these peptides. Due to their highly pharmacological potency and target selectivity, Conus peptides have attracted extensive attention with their potentials to be developed as new research tools in neuroscience field and as novel medications in clinic for pain, epilepsy and other neuropathic disorders. Several instructive lessons for our drug development could be also learnt from these neuropharmacological "expertises". Conus peptides comprise a rich resource for neuropharmacologists, and most of them await to be explored.