gebhart/patrepeval huggingface dataset:
Sox9: A Master Regulator of the Pancreatic Program (2014)

Over the last decade, it has been discovered that the transcription factor Sox9 plays several critical roles in governing the development of the embryonic pancreas and the homeostasis of the mature organ. While analysis of pancreata from patients affected by the Sox9 haploinsufficiency syndrome campomelic dysplasia initially alluded to a functional role of Sox9 in pancreatic morphogenesis, transgenic mouse models have been instrumental in mechanistically dissecting such roles. Although initially defined as a marker and maintenance factor for pancreatic progenitors, Sox9 is now considered to fulfill additional indispensable functions during pancreogenesis and in the postnatal organ through its interactions with other transcription factors and signaling pathways such as Fgf and Notch. In addition to maintaining both multipotent and bipotent pancreatic progenitors, Sox9 is also required for initiating endocrine differentiation and maintaining pancreatic ductal identity, and it has recently been unveiled as a key player in the initiation of pancreatic cancer. These functions of Sox9 are discussed in this article, with special emphasis on the knowledge gained from various loss-of-function and lineage tracing mouse models. Also, current controversies regarding Sox9 function in healthy and injured adult pancreas and unanswered questions and avenues of future study are discussed.
Quantitative titration of nucleic acids by enzymatic amplification reactions run to saturation (1993)

In vitro enzymatic amplification of nucleic acids by PCR or other techniques is a very sensitive method to detect rare DNA segments. We present here a protocol that allows the rapid, sensitive and precise quantification of DNA molecules using PCR amplification run to saturation. The DNA (or cDNA) to be assayed is co-amplified with known amounts of an internal standard DNA. We show that the latter must be almost identical to the assayed DNA, otherwise quantification at the plateau is unreliable. The read-out of the amplification involves one or two additional oligonucleotides. Using fluorescent oligonucleotides as primers in run-off reactions together with an automated DNA sequencer, we could measure the level of expression of several genes, like the murine MHC class I H-2Kd or a specific T cell receptor beta chain transcript in the course of an immunization. mRNA levels were normalized by measuring in a similar manner the number of transcripts encoding the housekeeping gene HPRT. Finally, our procedure might allow the rapid analysis of a large number of samples at the same time, as illustrated by the simultaneous analysis of the mRNAs encoding the CD4 and CD8 murine T cell markers.
Microneedles for transdermal delivery of macromolecules (2003)

Transdermal drug delivery is limited by the extraordinary barrier properties of the stratum corneum, the outer 10-15 /spl mu/m of skin. Arrays of solid silicon microneedles inserted across the stratum corneum have been shown to painlessly disrupt this barrier and increase the permeability of skin to calcein up to four orders of magnitude. In this study microneedles delivered bovine serum albumin (BSA) and insulin across human epidermis in vitro at similarly increased levels. To develop better microneedles, arrays of hollow silicon and metal needles have also been fabricated using microfabrication techniques including deep reactive ion etching, micromolding, and electroplating. The hollow needles have been successfully inserted through human epidermis and have been shown to permit water to flow through their bores.
L'Age du Bronze dans la région de La Guerche (Ille-et-Vilaine) (1986)

Deux dépôts de bronzes découverts dans la région de La Guerche à Moutiers et Domalain ont été découverts en 1965 et 1975. Us montrent la richesse du Bronze moyen de Haute-Bretagne avec les haches à talon de type breton et les bracelets décorés du type de Bignan. L'éventail des décors de ces derniers complète la connaissance du vieux style géométrique européen. Les analyses métallurgiques révèlent des bronzes à forte teneur en étain et faible proportion de plomb. L'inventaire des autres dépôts de la région a permis de rappeler un ensemble intéressant, celui de La Guerche qui comprend une pointe de Palmela "relique" en contexte du Bronze final à haches à douille et bracelets décorés.
Fifty Years of Diazeniumdiolate Research. From Laboratory Curiosity to Broad-Spectrum Biomedical Advances (2011)

Here I show that a "pure" research project, seemingly totally lacking in practical application when it was first published, can years later spark a whole new scientific field with the potential to revolutionize clinical practice. A 1961 publication describing adducts of nitric oxide (NO) with certain nucleophiles attracted little notice at the time, but later work showing that the adducts could be hydrolyzed to regenerate the NO in bioactive form has provided the foundation for a host of biomedical applications. Crucial to the discovery of widely used tools for studying NO's chemical biology as well as for the design of a variety of promising therapeutic advances has been the increasingly detailed understanding of the physicochemical properties of these "diazeniumdiolates" (also known as NONOates).
Up-regulation of a death receptor renders antiviral T cells susceptible to NK cell–mediated deletion (2012)

Antiviral T cell responses in hepatotropic viral infections such as hepatitis B virus (HBV) are profoundly diminished and prone to apoptotic deletion. In this study, we investigate whether the large population of activated NK cells in the human liver contributes to this process. We show that in vitro removal of NK cells augments circulating CD8(+) T cell responses directed against HBV, but not against well-controlled viruses, in patients with chronic hepatitis B (CHB). We find that NK cells can rapidly eliminate HBV-specific T cells in a contact-dependent manner. CD8(+) T cells in the liver microcirculation are visualized making intimate contact with NK cells, which are the main intrahepatic lymphocytes expressing TNF-related apoptosis-inducing ligand (TRAIL) in CHB. High-level expression of the TRAIL death receptor TRAIL-R2 is found to be a hallmark of T cells exposed to the milieu of the HBV-infected liver in patients with active disease. Up-regulation of TRAIL-R2 renders T cells susceptible to caspase-8-mediated apoptosis, from which they can be partially rescued by blockade of this death receptor pathway. Our findings demonstrate that NK cells can negatively regulate antiviral immunity in chronic HBV infection and illustrate a novel mechanism of T cell tolerance in the human liver.
Compensation of motion artifacts in catheter-based optical frequency domain imaging (2010)

A novel heterodyne Doppler interferometer method for compensating motion artifacts caused by cardiac motion in intracoronary optical frequency domain imaging (OFDI) is demonstrated. To track the relative motion of a catheter with regard to the vessel, a motion tracking system is incorporated with a standard OFDI system by using wavelength division multiplexing (WDM) techniques. Without affecting the imaging beam, dual WDM monochromatic beams are utilized for tracking the relative radial and longitudinal velocities of a catheter-based fiber probe. Our results demonstrate that tracking instantaneous velocity can be used to compensate for distortion in the images due to motion artifacts, thus leading to accurate reconstruction and volumetric measurements with catheter-based imaging.
Design, construction, and two applications for an automated flow-cell polarization fluorometer with digital read out: enzyme-inhibitor (antitrypsin) assay and antigen-antibody (insulin-insulin antiserum) assay. (1973)

We have constructed and automated a flow cell polarization fluorometer and demonstrated two specific clinical applications of fluorescence polarization assay, i.e., the enzyme-inhibitor assay of antitrypsin in serum and the antigen-antibody assay of insulin and its antibody. A signal is displayed directly and is immediately available for chart recording and (or) digital data processing. Since fluorescence polarization offers a number of choices in assay parameters and the use of different fluorescent probes, its development for rapid simultaneous measurements of multiple components in body fluids should be possible.
Cardiovascular Effects of Eugenol, a Phenolic Compound Present in Many Plant Essential Oils, in Normotensive Rats (2004)

Cardiovascular effects of intravenous (i.v.) treatment with eugenol (Eug), a natural pungent present in many plant essential oils, were investigated in normotensive rats. In either anesthetized or conscious rats, i.v. bolus injections of Eug (1 to 10 mg/kg) elicited immediate and dose-dependent hypotension and bradycardia. Magnitude of Eug-induced hypotension was similar in both groups. Pretreatment of anesthetized rats with bilateral vagotomy almost abolished the bradycardic responses to Eug without affecting the hypotension. Likewise, i.v. pretreatment of conscious rats with methylatropine (1 mg/kg) or hexamethonium (30 mg/kg) significantly reduced the Eug-induced bradycardia without affecting the hypotension. However, i.v. pretreatment with the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl (L-NAME, 20 mg/kg), affected neither the hypotension nor the bradycardia elicited by Eug. In rat mesenteric bed preparations precontracted with potassium (60 mM), Eug (0.1-2 mM) induced a reversible and concentration-dependent vasodilator effect, which remained unaffected by atropine (1 microM). These results show that i.v. treatment of rats with Eug induces dose-dependent hypotension and bradycardia, which occurred independently. The bradycardia appears dependent upon the presence of an intact and functional parasympathetic nerve drive to the heart while the hypotension is due to an active vascular relaxation rather than withdrawal of sympathetic tone. Released nitric oxide from vascular endothelial cells seems to be not involved in the mediation of Eug-induced hypotension.
Topochemical Synthesis, Anion Exchange, and Exfoliation of Co−Ni Layered Double Hydroxides: A Route to Positively Charged Co−Ni Hydroxide Nanosheets with Tunable Composition (2009)

This paper describes the topochemical synthesis of Co−Ni layered double hydroxides (LDHs) from brucite-like Co−Ni hydroxides through a novel oxidative intercalation process employing bromine as an oxidizing agent, and their exfoliation into positively charged unilamellar nanosheets in formamide after anion-exchange treatment. In this protocol, hexagonal microplatelets of brucite-like Co−Ni hydroxides in variable composition were prepared by homogeneous precipitation of a mixed solution of divalent cobalt and nickel ions via hexamethylenetetramine hydrolysis. Subsequent treatment of the brucite-like Co−Ni hydroxides with excessive bromine in acetonitrile promoted partial oxidation of Co2+ into Co3+, producing Br−-intercalated Co−Ni LDHs inheriting the hexagonal morphology. This rational topochemical approach was applicable for realizing a pure phase of Co−Ni LDHs with nickel content up to 50% (metal content). Chemical analyses indicated that as-prepared Co−Ni−Br LDHs were unexceptionally characterized by a general chemical formula as [(Co2+1−3x/2Ni2+3x/2)2/3Co3+1/3(OH−)2][Br−1/3·0.5H2O] (x ≤ 0.5), a thermodynamically stable LDH structure with a M2+/M3+ ratio of 2:1. We developed an ethanol-assisted anion-exchange approach, which was effective in preventing carbonate contamination in preparing a variety of inorganic and organic anionic forms of Co−Ni LDHs. As-prepared NO3− intercalated Co−Ni LDHs without substantial carbonate contamination were successfully exfoliated into unilamellar nanosheets bearing positive charges upon contact with formamide. The translucent nanosheet suspensions exhibited characteristic colors depending on the variable Co/Ni ratio.
Carbon Nanotubes for Thin Film Transistor: Fabrication, Properties, and Applications (2013)

We review the present status of single‐walled carbon nanotubes (SWCNTs) for their production and purification technologies, as well as the fabrication and properties of single‐walled carbon nanotube thin film transistors (SWCNT‐TFTs). The most popular SWCNT growth method is chemical vapor deposition (CVD), including plasma‐enhanced chemical vapor deposition (PECVD), floating catalyst chemical vapor deposition (FCCVD), and thermal CVD. Carbon nanotubes (CNTs) used to fabricate thin film transistors are sorted by electrical breakdown, density gradient ultracentrifugation, or gel‐based separation. The technologies of applying CNT random networks to work as the channels of SWCNT‐TFTs are also reviewed. Excellent work from global researchers has been benchmarked and analyzed. The unique properties of SWCNT‐TFTs have been reviewed. Besides, the promising applications of SWCNT‐TFTs have been explored. Finally, the key issues to be solved in future have been summarized.
Natural killer cell cytotoxicity of breast cancer targets is enhanced by two distinct mechanisms of antibody-dependent cellular cytotoxicity against LFA-3 and HER2/neu (1999)

Treatment of advanced breast cancer with autologous stem cell transplantation is limited by a high probability of disease relapse. In clinical trials, interleukin 2 (IL-2) alone can expand natural killer (NK) cells in vivo and increase their cytotoxic activity against breast cancer cell lines, but this increase is modest. Understanding the mechanisms that mediate NK cell lysis of breast cancer targets may lead to improvements of current immunotherapy strategies. NK cells from normal donors or patients receiving subcutaneous IL-2 were tested in cytotoxicity assays against five breast cancer cell lines. The role of adhesion molecules and antibodies that interact through Fc receptors on NK cells was explored. NK cell lysis of breast cancer targets is variable and is partially dependent on recognition through ICAM-1 and CD18. While blocking CD2 slightly decreased cytotoxicity, contrary to expectations, an antibody against CD58 (the ligand for CD2), failed to block killing and instead mediated an increased cytotoxicity that correlated with target density of CD58. The CD58 antibody-enhanced killing was dependent not only on FcRgammaIII but also on CD2 and ICAM-1/CD18. To further elucidate the mechanism of this CD58 antibody-dependent cellular cytotoxicity (ADCC), another antibody was tested. Trastuzumab (Herceptin), a humanized antibody against HER2/neu, mediated potent ADCC against all the HER2/neu positive breast cancer targets. Unlike CD58 antibody-mediated ADCC, Herceptin ADCC was minimally affected by blocking antibodies to CD2 or ICAM-1/CD18, which suggests a different mechanism of action. This study shows that multiple mechanisms are involved in NK cell lysis of breast cancer targets, that none of the targets are inherently resistant to killing, and that two distinct mechanisms of ADCC can target immunotherapy to breast cancer cells.
Impact of human amniotic membrane preparation on release of angiogenic factors (2009)

Preserved amniotic membrane (AM) has been used in the field of ophthalmology and wound care due to its bacteriostatic, antiphlogistic, protease-inhibiting, re-epithelialization, wound-protecting and scar formation-reducing properties. Typically, AM is applied after banking in a glycerol-preserved or freeze-dried state. Cell viabilities in different forms of preparation vary substantially, which in consequence may also be reflected in the amount and type of growth factors released from the preserved material. Therefore, we characterized the angiogenic factor (AF) profile released from different AM preparations. For this, medium was conditioned with non-preserved, glycerol- and cryo-preserved AM for 48 h, which was screened for AFs using a protein array system. In parallel, the preparations were tested for cell viability. Non-preserved as well as cryo-preserved AM maintained viabilities at 106.5 +/- 23.9% and 21.9 +/- 23.3%, respectively, whereas glycerol-preserved AM was found to be non-viable. Of the 20 investigated factors, high levels of angiogenin, GRO, IL-6/8, TIMP-1/2 and MCP-1 and low levels of EGF, IFNgamma, IGF-1, leptin, RANTES, TGFbeta1 and thrombopoietin were identified to be secreted from non-preserved AM. Cryo-preserved AM secreted high levels of IL-8, intermediate levels of GRO and TIMP-1/2 but only low levels of angiogenin, IFNgamma, IL-6 and MCP-1 and no detectable EGF, IGF-1, leptin, RANTES, TGFbeta1 and thrombopoietin. After banking in glycerol, AM releases only minute amounts of TIMP-1/2. Along with viability, the AF profile of amniotic membrane largely depends on the preparation method applied for banking. This should be considered for selection of an AM product for a specific clinical application.
Defining the genetic origins of three rheumatoid synovium-derived IgG rheumatoid factors. (1994)

A major diagnostic marker in most rheumatoid arthritis (RA) patients is the rheumatoid factor (RF), an autoantibody that binds to the Fc region of IgG. To delineate the Ig genes and the underlying mechanism for RF production in RA patients, we applied a systematic approach to define the genetic origins of three IgG RFs derived from the synovial fluid of two RA patients. The results show that two of three IgG RF have substantial numbers of somatic mutations in their variable (V) regions, ranging from 13 to 23 mutations over a stretch of 291-313 nucleotides, resulting in a frequency of 4.4-7.8%. However, one IgG RF has only one mutation in each V region. This result indicates that an IgG RF may arise from a germline gene by very few mutations. The mutations occur mainly in the complementarity-determining regions (CDRs), and the mutations in the CDRs often lead to amino acid substitutions. Five of the six corresponding germline V genes have been found to encode either natural autoantibodies or autoantibodies in other autoimmune disorders; and three of the six V genes have been found in fetal liver. Taken together with other results, the data show that (a) several potentially pathogenic RFs in RA patients arise from natural autoantibodies, and (b) only a few mutations are required to convert the natural autoantibodies to IgG RFs.
Prolonged Reduction of High Blood Pressure With an In Vivo, Nonpathogenic, Adeno-Associated Viral Vector Delivery of AT 1 -R mRNA Antisense (1997)

To produce a prolonged decrease in blood pressure, we have developed a nonpathogenic adeno-associated viral vector (AAV) with the antisense DNA for AT1-R. AAV has many advantages over other viral vectors. AAV does not stimulate inflammation or immune reaction. AAV enters nondividing cells and does not replicate. Therefore, it is an appropriate choice for gene therapy. Recombinant AAV was prepared with a cassette containing a cytomegalovirus promoter and the cDNA for the AT1 receptor inserted in the antisense direction. The cassette was packaged in the virion. Stable transfection of NG108-15 cells with the PAAV-AS (plasmid AAV) antisense to AT1-R produced a significant reduction in AT1 receptors. A single injection of the rAAV-AS (viral vector) was made in adult spontaneously hypertensive rats, either directly in the hypothalamus (1 microL) or in the lateral ventricles (5 microL). The result shows that there is a significant decrease of blood pressure (approximately 23 +/- 2 mm Hg) for up to 9 weeks after injection. Control injections of mock vector produced no change in blood pressure during the same time period in age-matched controls. In young spontaneously hypertensive rats (3 weeks), a single intracardiac injection of recombinant rAAV-AS reduced blood pressure and slowed the development of hypertension compared with controls (P < .01). The results suggest that a prolonged reduction in high blood pressure can be achieved with AAV vectors delivering antisense to inhibit AT1 receptors with a single administration.
KDIGO Clinical Practice Guidelines for Acute Kidney Injury (2012)

tion’, implying that most patients ‘should’ receive a particular action. In contrast, level 2 guidelines are essentially ‘suggestions’ and are deemed to be ‘weak’ or discretionary, recognising that management decisions may vary in different clinical contexts. Each recommendation was further graded from A to D by the quality of evidence underpinning them, with grade A referring to a high quality of evidence whilst grade D recognised a ‘very low’ evidence base. The overall strength and quality of the supporting evidence is summarised in table 1 . The guidelines focused on 4 key domains: (1) AKI definition, (2) prevention and treatment of AKI, (3) contrastinduced AKI (CI-AKI) and (4) dialysis interventions for the treatment of AKI. The full summary of clinical practice statements is available at www.kdigo.org, but a few key recommendation statements will be highlighted here.
Activation of JAK-STAT pathway is required for platelet-derived growth factor-induced proliferation of pancreatic stellate cells (2005)

PDGF-BB activated JAK2-STAT pathway via Src-dependent mechanism. Activation of JAK2-STAT3 pathway, in addition to ERK, may play a role in PDGF-induced proliferation of PSCs.
A Possible Role for Calcitonin-Gene-Related Peptide in the Regulation of the Smooth Muscle Tone of the Bladder and Penis (1990)

We investigated the effect of calcitonin-gene-related peptide (CGRP) on bladder contractions and penile erection in 12 dogs. In a system in which the arteries were tied bilaterally to ensure delivery of high drug levels to the bladder, arterial injections of CGRP significantly reduced the peak intravesical pressure of bladder contractions induced by pelvic nerve stimulation or arterial injection of carbachol. When given intravenously, CGRP had no effect on bladder contractions consequent to neural stimulation. Intravesical instillation of CGRP, however, reduced the bladder contractions significantly. Histologic staining showed CGRP-immunoreactive nerve fibers within the smooth muscle layers of the bladder wall. Intracavernous CGRP increased cavernous arterial flow and induced cavernous smooth muscle relaxation and venous outflow occlusion. Muscarinic blockade had no effect on the canine intracavernous pressure response to intracavernous injection of CGRP. Histologic staining for CGRP-immunoreactivity showed nerve-fiber-like staining within the cavernous arterial wall, the nerves running near the cavernous arteries, and the cavernous smooth muscles. Our results suggest a possible role for CGRP in the regulation of the smooth muscle tone of the bladder and penis.
Frustrated energy transport through micro-waveguides decorated by gold nanoparticle chains (2004)

This letter reports near-field optical observations of light energy transport along micro-waveguides decorated by short chains of gold "nanodots". In spite of their subwavelength dimensions (100 nm diameter ×20 nm height), the metallic dots in the chain function as an efficient photonic band filter or a nanometric Bragg mirror. Numerical simulations reproduce the observed phenomenon and indicate that the occurrence of a band gap for light transport through the decorated guide corresponds to a selective absorption by the metallic chain.
Symbolic guided search for CTL model checking (2000)

CTL model checking of complex systems often suffers from the state-explosion problem. We propose using Symbolic Guided Search to avoid difficult-to-represent sections of the state space and prevent state explosion from occurring.