gebhart/patrepeval huggingface dataset:
Enhanced Healing of Diabetic Wounds by Topical Administration of Adipose Tissue-Derived Stromal Cells Overexpressing Stromal-Derived Factor-1: Biodistribution and Engraftment Analysis by Bioluminescent Imaging (2010)

Chronic ulcers represent a major health problem in diabetic patients resulting in pain and discomfort. Conventional therapy does not guarantee adequate wound repair. In diabetes, impaired healing is partly due to poor endothelial progenitor cells mobilisation and homing, with altered levels of the chemokine stromal-derived factor-1 (SDF-1) at the wound site. Adipose tissue-associated stromal cells (AT-SCs) can provide an accessible source of progenitor cells secreting proangiogenic factors and differentiating into endothelial-like cells. We demonstrated that topical administration of AT-SCs genetically modified ex vivo to overexpress SDF-1, promotes wound healing into diabetic mice. In particular, by in vivo bioluminescent imaging analysis, we monitored biodistribution and survival after transplantation of luciferase-expressing cells. In conclusion, this study indicates the therapeutic potential of AT-SCs administration in wound healing, through cell differentiation, enhanced cellular recruitment at the wound site, and paracrine effects associated with local growth-factors production.
State-of-the-Art Management for the Patient with Castration-Resistant Prostate Cancer in 2012 (2012)

Much progress has been made in metastatic castration-resistant prostate cancer (CRPC), and multiple new U.S. Food and Drug Administration (FDA)-approved survival-prolonging drugs are now available. In 2004, docetaxel/prednisone was the first therapy shown to prolong survival. In 2010 and 2011, sipuleucel-T, cabazitaxel/prednisone, and abiraterone/prednisone were FDA approved. Two new agents, radium-223 and MDV-3100, have recently reported large phase III trials prolonging overall survival and will be submitted for regulatory approval in 2012. One can now begin to ask, is there an optimal sequence for therapies in metastatic CRPC? Despite the recent progress, there is much we do not know and virtually no information on this important question. We know that abiraterone/prednisone and cabazitaxel/prednisone are appropriate choices for a patient after receiving docetaxel, but we do not know what, if anything, represents the optimal sequence for abiraterone and cabazitaxel. In fact we do not understand how one therapy may affect the response to a subsequent therapy. We are also aware that the pre- and postdocetaxel spaces represent regulatory rather than biologic divisions. In addition, despite the proven role of docetaxel/prednisone, many patients with CRPC are not considered to be suitable for chemotherapy, and worldwide many never receive any form of chemotherapy. What is the optimal management for these patients? Taken together it is reasonable to assess patient preferences, prior therapies and response/tolerance to prior therapies, burden of disease, comorbidities, current symptoms, drug toxicities, out-of-pocket costs, etc., in clinical decision making. Given the many factors we do not know, it is hard to be dogmatic in approaching the therapeutic options for the patient with CRPC. We will likely soon move beyond the current sequencing paradigm and begin to assess new combinations in a systematic and rational fashion. Perhaps one day, in the not too distant future, we will develop molecular "stratification systems" to better guide therapeutic choices in CRPC.
Mechanism of enhanced light output efficiency in InGaN-based microlight emitting diodes (2003)

Micro-light emitting diode (LED) arrays with diameters of 4 to 20 μm have been fabricated and were found to be much more efficient light emitters compared to their broad-area counterparts, with up to five times enhancement in optical power densities. The possible mechanisms responsible for the improvement in performance were investigated. Strain relaxation in the microstructures as measured by Raman spectroscopy was not observed, arguing against theories of an increase in internal quantum efficiency due to a reduction of the piezoelectric field put forward by other groups. Optical microscope images show intense light emission at the periphery of the devices, as a result of light scattering off the etched sidewalls. This increases the extraction efficiency relative to broad area devices and boosts the forward optical output. In addition, spectra of the forward emitted light reveal the presence of resonant cavity modes [whispering gallery (WG) modes in particular] which appear to play a role in enhancing the optical output.
Mechanistic study on the cytostatic and tumor cell differentiation-inducing properties of 9-(2-phosphonylmethoxyethyl)adenine (PMEA, adefovir)-collected publications. (2000)

The therapeutic potential of the antiretroviral drug 9-(2-phosphonylmethoxyethyl)adenine (PMEA, adefovir) for the treatment of human immunodeficiency virus (HIV)- and human hepatitis B virus (HBV) infections is currently being explored in advanced clinical trials. In the present study, we investigated the impact of PMEA on cellular functioning (cell cycle, nucleotide metabolism, nucleic acid synthesis, ...). Moreover, we have unraveled the molecular/biochemical basis underlying the marked differentiation-inducing activity of PMEA (and related analogues) in tumor cells. We could demonstrate that PMEA is endowed with potent antitumor activity in a highly aggressive in vivo tumor model. These findings open new perspectives for the possible application of this type of compounds in cancer chemotherapy. The fact that AIDS patients frequently develop certain types of differentiation-susceptible malignancies (e.g. Kaposi's sarcoma) further attests the clinical relevance of our observations.
Development of dengue vaccine. (2000)

The dengue viruses are estimated to cause several hundred thousand cases of dengue fever, dengue haemorrhagic fever and dengue shock syndrome annually. Attempts to prevent the infection focus on the development of a vaccine that would protect against all four serotypes of the dengue virus. Various biotechnological approaches are being explored, including the use of live attenuated or inactivated viruses, infectious clone-derived vaccines, immunogens vectored by various recombinant systems, subunit immunogens and nucleic acid vaccine. Three candidate vaccines are undergoing clinical evaluation and several are at the stage of pre-clinical evaluation. A WHO steering committee is conducting activities aimed at accelerating the development of vaccines against dengue and Japanese encephalitis.
Enzymic analysis of the crabtree effect in glucose-limited chemostat cultures of Saccharomyces cerevisiae (1989)

The physiology of Saccharomyces cerevisiae CBS 8066 was studied in glucose-limited chemostat cultures. Below a dilution rate of 0.30 h-1 glucose was completely respired, and biomass and CO2 were the only products formed. Above this dilution rate acetate and pyruvate appeared in the culture fluid, accompanied by disproportional increases in the rates of oxygen consumption and carbon dioxide production. This enhanced respiratory activity was accompanied by a drop in cell yield from 0.50 to 0.47 g (dry weight) g of glucose-1. At a dilution rate of 0.38 h-1 the culture reached its maximal oxidation capacity of 12 mmol of O2 g (dry weight)-1 h-1. A further increase in the dilution rate resulted in aerobic alcoholic fermentation in addition to respiration, accompanied by an additional decrease in cell yield from 0.47 to 0.16 g (dry weight) g of glucose-1. Since the high respiratory activity of the yeast at intermediary dilution rates would allow for full respiratory metabolism of glucose up to dilution rates close to mumax, we conclude that the occurrence of alcoholic fermentation is not primarily due to a limited respiratory capacity. Rather, organic acids produced by the organism may have an uncoupling effect on its respiration. As a result the respiratory activity is enhanced and reaches its maximum at a dilution rate of 0.38 h-1. An attempt was made to interpret the dilution rate-dependent formation of ethanol and acetate in glucose-limited chemostat cultures of S. cerevisiae CBS 8066 as an effect of overflow metabolism at the pyruvate level. Therefore, the activities of pyruvate decarboxylase, NAD+- and NADP+-dependent acetaldehyde dehydrogenases, acetyl coenzyme A (acetyl-CoA) synthetase, and alcohol dehydrogenase were determined in extracts of cells grown at various dilution rates. From the enzyme profiles, substrate affinities, and calculated intracellular pyruvate concentrations, the following conclusions were drawn with respect to product formation of cells growing under glucose limitation. (i) Pyruvate decarboxylase, the key enzyme of alcoholic fermentation, probably already is operative under conditions in which alcoholic fermentation is absent. The acetaldehyde produced by the enzyme is then oxidized via acetaldehyde dehydrogenases and acetyl-CoA synthetase. The acetyl-CoA thus formed is further oxidized in the mitochondria. (ii) Acetate formation results from insufficient activity of acetyl-CoA synthetase, required for the complete oxidation of acetate. Ethanol formation results from insufficient activity of acetaldehyde dehydrogenases.(ABSTRACT TRUNCATED AT 400 WORDS)
Gene Therapy Chronology (1996)

Eliot Marshall states in his response to Robert J. Levine (Letters, [24 May, p. 1085][1]) that I “told Levine in June 1995 that [I] did not foresee any possibility of a human trial,” although this is clearly contradicted by Levine's statement “that the [ New York Times ] story was premature
Cloning and expression of Clostridium acetobutylicum phosphotransbutyrylase and butyrate kinase genes in Escherichia coli (1988)

A 13.6-kilobase (kb) Sau3AI restriction endonuclease fragment of Clostridium acetobutylicum DNA cloned into pBR322 enabled Escherichia coli ato mutants to grow on butyrate as a sole carbon source (But+). Complementation of the ato defect by the recombinant plasmid pJC6 was due to expression of the genes for phosphotransbutyrylase (PTB) and butyrate kinase (BK). Both genes were efficiently expressed in E. coli, as their products were readily detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of whole-cell extracts. PTB was found to have a polypeptide subunit molecular weight of approximately 31,000, while that of BK was approximately 39,000. Deletion analysis and Tn5 mutagenesis of plasmid pJC7 (a But+ subclone containing a 4.4-kb BamHI fragment from the insert of pJC6) localized the PTB and BK genes within a region spanning approximately 2.9 kb. Preliminary evidence suggests that the two genes may form an operon that is transcribed as a single unit from a promoter of clostridial origin within the 4.4-kb insert of pJC7.
A DEVICE FOR RECORDING LEFT VENTRICULAR CONTRACTION AND ELECTROCARDIOGRAM IN NONWORKING ISOLATED PERFUSED RAT HEART (1978)

Using the isolated Langendorff rat heart preparation perfused at a constant flow rate (about 6 ml.min-1 pro heart) with a modified Krebs-Henseleit solution, methods for recording left ventricular cavity pressure and electrocardiogram (ECG) changes were devised. Stable levels of mechanical activities were reached 60--90 min after start of perfusion and were maintained for at least 4 hr. When either norepinephrine (0.05--0.15 microgram) was injected into the aortic bulb of the heart, sensitive changes in the measurable cardiac parameters were observed and changes in ECG patterns were particularly characteristic. Our results indicate that this experimental model may be useful for evaluating numerous functions of the isolated heart.
Rigorous surface enhanced Raman spectral characterization of large-area high-uniformity silver-coated tapered silica nanopillar arrays (2010)

Surface enhanced Raman spectroscopy (SERS) has been increasingly utilized as an analytical technique with significant chemical and biological applications (Qian et al 2008 Nat. Biotechnol. 26 83; Fujita et al 2009 J. Biomed. Opt. 14 024038; Chou et al 2008 Nano Lett.8 1729; Culha et al 2003 Anal. Chem. 75 6196; Willets K A 2009 Anal. Bioanal. Chem. 394 85; Han et al 2009 Anal. Bioanal. Chem. 394 1719; Sha et al 2008 J. Am. Chem. Soc. 130 17214). However, production of a robust, homogeneous and large-area SERS substrate with the same ultrahigh sensitivity and reproducibility still remains an important issue. Here, we describe a large-area ultrahigh-uniformity tapered silver nanopillar array made by laser interference lithography on the entire surface of a 6 inch wafer. Also presented is the rigorous optical characterization method of the tapered nanopillar substrate to accurately quantify the Raman enhancement factor, uniformity and repeatability. An average homogeneous enhancement factor of close to 10(8) was obtained for benzenethiol adsorbed on a silver-coated nanopillar substrate.
Spatial clustering of SARS in Hong Kong. (2009)

1. Geographic information system (GIS) can be applied during an acute infectious disease outbreak to reveal new geospatial information in addition to standard field epidemiological analyses. 2. When applied in real time during the onset and evolution of an epidemic, GIS can monitor and enhance understanding of the transmission dynamics of an infectious agent, thereby facilitating the design, implementation and evaluation of potential intervention strategies.
Proteosome-hydrophobic ‘foot’ malaria peptide vaccines for Plasmodium falciparum and P. vivax (1989)

The immunogenicity of synthetic peptides representing the repeating portions of circumsporozoite proteins of Plasmodium sporozoites was greatly increased by complexing them to proteosomes via hydrophobic moieties added to their amino termini. Proteosomes have been used safely in people in the development of meningococcal vaccines and therefore proteosome-peptide vaccines are prime candidates for use against malaria.
pH-Sensitivity of the E3/K3 Heterodimeric Coiled Coil (2008)

This manuscript reports on the self-assembly properties of two complementary peptide sequences, E3 and K3, which are derived from the known IAAL E3/K3 heterodimeric coiled coil motif. Circular dichroism spectroscopy, analytical ultracentrifugation, and fluorescence resonance energy transfer experiments indicated that a stoichiometric mixture of these two peptides forms a stable heterodimeric coiled coil at pH 7. At pH 5, in contrast, the E3/K3 heterodimeric coiled coil is unstable and unfolds to generate E3 homotrimers that coexist with K3 unimers and a small fraction of K3 homodimers. This pH-induced unfolding transition was unprecedented for this coiled coil motif but is of interest as it occurs within a physiologically relevant pH range, as it is encountered, for example, during cellular uptake via the endosomal pathway. This feature, in combination with the relatively short length of the E3 and K3 peptides and the high stability of the E3/K3 coiled coil at pH 7 makes this folding motif very attractive for the development of noncovalent polymer therapeutics and self-assembled biohybrid hydrogels.
Ischemia-reperfusion injury-induced histological changes affecting early stage pressure ulcer development in a rat model. (2011)

﻿﻿﻿Pressure ulcers (PU) are caused by the interplay of multiple factors including skin microcirculation. Ischemia-reperfusion (I/R) injury is considered a significant mechanism in the early stages of pressure ulcer development. The objective of this controlled, single-blinded in vivo study was to create a pressure-induced injury rat animal model and explore the possible mechanism and effects of I/R injury in early stage PU development using clinically relevant amounts of pressure and pressure duration. Forty-eight animals were randomly divided into six groups of eight and a 2.5 cmx2.5 cm area of the hip was subjected to no pressure (control), ischemia only (IG--2 hours of 70 mm Hg pressure), or one of four I/R cycles (70 mm HG of pressure for 2 hours followed by 1, 2, 3, or 4 hours of reperfusion). All I/R cycles were repeated three times. Full-thickness skin samples from the compressed area were harvested for histopathology and femoral artery blood samples obtained to measure serum levels of the following inflammatory mediators: malondialdehyde (MDA), superoxide dismutase (SOD) nitric oxide (NO) and endothelin-1 (ET-1). MDA, NO, and ET-1 levels were significantly higher in the IR than the control (P<0.01) and ischemia groups (P<0.05); whereas, SOD activity was significantly lower than in the IG and control groups (P<0.05). The largest differences were observed in the 2-hour ischemia/3-hour reperfusion group. Biopsy analysis by lightmicroscopy stain showed no changes in the control, mild changes in the IG, and considerable damage, including leukocyte infiltration, collagen fibrosis, and edema in epidermal, dermal, and muscle tissue from the I/R group. These findings suggest that hypoxic-ischemic tissue injury occurs early following a period of ischemia and that I/R may be an important mechanism in PU development. Although the mechanisms of I/R injury are probably multifactorial and the actions of free radicals may be more complicated in the early stages of PU development in humans, the findings suggest that a minimum of 4 hours pressure relief may be helpful for PU prevention. Research to elucidate these mechanisms and their potential interactive effects to help clinicians develop evidence-based prevention protocols are warranted.
Cloning and Characterization of the Human Selenoprotein P Promoter (1997)

We isolated an 18-kilobase (kb) genomic selenoprotein P clone from a human placenta library and cloned, sequenced, and characterized the 5'-flanking region of the human selenoprotein P gene. Sequence analysis revealed an intron between base pairs (bp) -13 and -14 upstream of the ATG codon and another one between bp 534 and 535 of the coding region. The major transcription start site of selenoprotein P in human HepG2 hepatocarcinoma cells was mapped to bp -70 by 5'-rapid amplification of cDNA ends and by primer extension. 1.8 kb of the 5'-flanking sequence were fused to a luciferase reporter gene. They exhibited functional promoter activity in HepG2 hepatocarcinoma and Caco2 colon carcinoma cells in transient transfection experiments. Treatment of transfected HepG2 cells with the cytokines interleukin 1beta, tumor necrosis factor alpha, and interferon gamma repressed promoter activity. Nuclear extracts of interferon gamma-treated cells bound to a signal transducer and activator of transcription response element of the promoter in gel retardation experiments. By transfection of promoter-deletion constructs, a TATA box and a putative SP1 site were identified to be necessary for selenoprotein P transcription. These data indicate that the human selenoprotein P gene contains a strong promoter that is cytokine responsive. Furthermore, selenoprotein P, secreted by the liver, might react as a negative acute phase protein.
High- and low-affinity binding of GRO alpha and neutrophil-activating peptide 2 to interleukin 8 receptors on human neutrophils. (1992)

GRO alpha and neutrophil-activating peptide 2 (NAP-2), like their analog interleukin 8 (IL-8), are considered to be inflammatory mediators since they recruit and activate neutrophil leukocytes. After introduction of tyrosines by substitution for other residues at the C terminus, GRO alpha and NAP-2 were labeled with 125I and used for binding studies. A total of 60,000-90,000 receptors per neutrophil were found for either ligand. Of these 30-45% were of high affinity with a mean Kd value of 0.3 and 0.7 nM for GRO alpha and NAP-2, respectively, and 55-70% of low affinity (Kd = 30 nM). Two proteins of approximately 70 kDa and 44 kDa (p70 and p44) were specifically cross-linked with labeled GRO alpha, NAP-2, and IL-8. Unlabeled IL-8 fully inhibited this cross-linking and the binding of labeled GRO alpha or NAP-2 to the high-affinity sites on neutrophils or neutrophil membranes. Treatment of membranes with digitonin resulted in the preferential solubilization of a single receptor species, corresponding to p44, that bound GRO alpha and NAP-2 with low affinity (Kd = 30 nM) and IL-8 with high affinity (Kd = 0.4 nM). Exposure of neutrophil membranes to 100 microM guanosine 5'-[gamma-thio]triphosphate led to a 75-fold increase of the Kd in approximately 60% of the IL-8 receptors. High-affinity receptors for GRO alpha and NAP-2 were similarly affected. In contrast, guanosine 5'-[gamma-thio]triphosphate had no effect on the binding of IL-8 to p44 solubilized by digitonin. These results demonstrate that human neutrophils bear two classes of receptors for GRO alpha, NAP-2, and IL-8 (p70 and p44) that may differ in their mode of interaction with GTP regulatory proteins.
Second-harmonic generation and optical stabilization of a diode laser in an external ring resonator (1990)

The second harmonic of the 842-nm output of a GaAlAs diode laser is generated in a KNbO(3) crystal in a resonant, external ring cavity. The diode laser is optically stabilized to the ring cavity through feedback from the counterpropagating fundamental wave, which is weakly excited in the resonator. We have produced 6.7 mW of tunable, narrowband radiation at 421 nm and have used that light to perform saturation spectroscopy on narrow transitions in rubidium.
Advances in High-Field Magnetic Resonance Imaging (2004)

Among advances in magnetic resonance imaging (MRI), the increase of the magnetic field strength is perhaps one of the most significant. The use of high magnetic fields for in vivo magnetic resonance is motivated by a number of considerations. Advantages are increases in signal-to-noise ratio, blood-oxygenation level-dependent contrast, and spectral resolution, while disadvantages include potential reduction of contrast in anatomic imaging owing to lengthening of T1 and effects of susceptibility of high fields. To address these challenges, technical advances have been made in various aspects of MRI, allowing high-field MRI to provide exquisite morphological and functional details in clinical and research settings. This review provides an overview of technical issues and applications of high-field MRI.
Isolation of a human stromal cell strain secreting hemopoietic growth factors (1986)

A diploid fibroblastoid cell strain, termed "ST-1," has been established from a long-term liquid culture of human fetal liver cells. ST-1 cells are nonphagocytic, nonspecific esterase negative and do not possess factor VIII-related antigen but stain with antibodies specific for fibronectin and type I collagen. The ST-1 cells produce nondialyzable hemopoietic growth factors capable of stimulating the development of erythroid bursts, mixed granulocyte-macrophage colonies, pure granulocyte colonies, and pure macrophage colonies. These factors are active on both human fetal liver and human adult bone marrow progenitors. When liquid cultures of human fetal liver hemopoietic progenitors are established with a preformed monolayer of ST-1 cells, the yields of nonadherent cells, erythroid progenitors, and myeloid progenitors are greatly increased. These studies demonstrate that the fibroblastoid ST-1 cells support hemopoiesis in vitro and may be a critical element in the stromal microenviroment in vivo.