gebhart/patrepeval huggingface dataset:
Molecular biology of prostate cancer progression. (1995)

A number of genetic changes have been documented in prostate cancer, ranging from allelic loss to point mutations and changes in DNA methylation patterns (summarized in Fig. 1). The most consistent changes seen are those of allelic loss events, with the majority of tumours examined showing loss of alleles from at least one chromosomal arm. The short arm of chromosome 8, followed by the long arm of chromosome 16, seem to be the most frequent regions of loss, suggesting the presence of novel tumour suppressor genes. Deletions of one copy of the RB and TP53 genes are less frequent as are mutations of the TP53 gene, and accumulating evidence suggests the presence of an additional tumour suppressor gene on chromosome 17p, which is frequently inactivated in prostate cancer. Alterations in the E-cadherin/alpha catenin mediated cell-cell adhesion mechanism appear to be present in almost half of all prostate cancers and may be critical to the acquisition of metastatic potential of aggressive prostate cancers. Finally, altered DNA methylation patterns have been found in the majority of prostate cancers examined, suggesting widespread alterations in methylation modulated gene expression. The presence of multiple changes in these tumours is consistent with the multistep nature of the transformation process. Finally, efforts to identify prostate cancer susceptibility loci are under way, which may elucidate critical early events in prostatic carcinogenesis.
Support of human cord blood progenitor cells on human stromal cell lines transformed by SV40 large T antigen under the influence of an inducible (metallothionein) promoter (1992)

Abstract We describe the development of a human bone marrow (BM) culture system which allows study of the interaction of stromal cell lines (SCL) and highly purified hematopoietic progenitor cells. Normal BM stromal cells were electroporated with a plasmid containing the simian virus 40 (SV40) large T antigen (SV40 T Ag) under the control of a synthetic metallothionein promoter (MT4); this construct is designated MT4 SV40 T Ag. SCL in which the rate of proliferation could be controlled by altering the zinc (Zn) concentration were characterized, demonstrating that the SCL were heterogeneous with respect to G-CSF and GM-CSF production. Suppression of SCL proliferation on removal of Zn made it possible to use these lines in coculture with purified CD34+ progenitor cells from umbilical cord blood. The ability to control proliferation of SCL has allowed us to maintain the survival and expansion of colony- forming cells in culture for up to 2 months. These lines have enabled us to test for stromal cell characteristics at a clonal level and provided us with a tool to analyze the events leading to lineage commitment and hematopoietic differentiation, as demonstrated by suppression of hematopoiesis by an antibody directed against the c-kit molecule.
Measurement of MMP-9 and -12 degraded elastin (ELM) provides unique information on lung tissue degradation (2012)

MMP-9 and -12 time-dependently released the ELN-441 epitope from elastin. This fragment was elevated in serum from patients with the lung diseases IPF and COPD, however these data needs to be validated in larger clinical settings.
Antibody-Targeted NY-ESO-1 to Mannose Receptor or DEC-205 In Vitro Elicits Dual Human CD8+ and CD4+ T Cell Responses with Broad Antigen Specificity (2010)

Immunization of cancer patients with vaccines containing full-length tumor Ags aims to elicit specific Abs and both CD4(+) and CD8(+) T cells. Vaccination with protein Ags, however, often elicits only CD4(+) T cell responses without inducing Ag-specific CD8(+) T cells, as exogenous protein is primarily presented to CD4(+) T cells. Recent data revealed that Ab-mediated targeting of protein Ags to cell surface receptors on dendritic cells could enhance the induction of both CD4(+) and CD8(+) T cells. We investigated in this study if these observations were applicable to NY-ESO-1, a cancer-testis Ag widely used in clinical cancer vaccine trials. We generated two novel targeting proteins consisting of the full-length NY-ESO-1 fused to the C terminus of two human mAbs against the human mannose receptor and DEC-205, both internalizing molecules expressed on APC. These targeting proteins were evaluated for their ability to activate NY-ESO-1-specific human CD4(+) and CD8(+) T cells in vitro. Both targeted NY-ESO-1 proteins rapidly bound to their respective targets on APC. Whereas nontargeted and Ab-targeted NY-ESO-1 proteins similarly activated CD4(+) T cells, cross-presentation to CD8(+) T cells was only efficiently induced by targeted NY-ESO-1. In addition, both mannose receptor and DEC-205 targeting elicited specific CD4(+) and CD8(+) T cells from PBLs of cancer patients. Receptor-specific delivery of NY-ESO-1 to APC appears to be a promising vaccination strategy to efficiently generate integrated and broad Ag-specific immune responses against NY-ESO-1 in cancer patients.
Generation of Functional Human Dendritic Cells From Adherent Peripheral Blood Monocytes by CD40 Ligation in the Absence of Granulocyte-Macrophage Colony-Stimulating Factor (1998)

Recently it has been shown that dendritic cells (DC) can develop from peripheral blood monocytes when grown in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). However, it is unclear whether DC can also develop from monocytes in absence of these cytokines. We therefore analyzed the effect of Flt-3 ligand (Flt3L) and of CD40 ligand on the development of human DC from blood monocytes in the absence of GM-CSF. Adherent peripheral blood mononuclear cells (PBMNC) were cultured in the presence of different cytokine combinations and analyzed for the expression of surface molecules and antigen presenting capacity. For functional analyses, cells were tested for their ability to stimulate allogeneic T lymphocytes in a mixed lymphocyte reaction (MLR), to present soluble antigens, and to induce primary HIV-peptide-specific cytotoxic T-cell (CTL) responses in vitro. Furthermore, expression of DC-CK1, a recently identified chemokine with specific expression in DC, and of IL-18 (IGIF), a growth and differentiation factor for Th 1 lymphocytes, was analyzed by reverse-transcription polymerase chain reaction (RT-PCR). In our study, Flt3L alone was not sufficient to generate DC and required addition of IL-4. DC generated with Flt3L and IL-4 underwent maturation after stimulation with tumor necrosis factor- (TNF-) or CD40L, characterized by CD83 expression, upregulation of MHC, adhesion, and costimulatory molecules as well as increased allogeneic proliferative response. In contrast, CD40 ligation alone promoted differentiation of adherent blood monocytes into functional DC in the absence of GM-CSF and IL-4. These cells displayed all phenotypic and functional characteristics of mature DC and were potent stimulatory cells in priming of major histocompatibility complex (MHC) class I-restricted CTL responses against an HIV-peptide, whereas their ability to present soluble protein antigens was reduced. Using a semiquantitative RT-PCR, DC-CK1 and IL-18 transcripts were detected in all generated DC populations, independent of growth factors used. Our findings provide further evidence for the importance of CD40-CD40L interaction for initiation and maintenance of T-cell responses and confirm the emerging concept that blood monocytes provide an additional source of DC depending on external stimuli.
Transgenic expression of survivin in keratinocytes counteracts UVB-induced apoptosis and cooperates with loss of p53 (2001)

The inhibitor of apoptosis protein survivin has been implicated in both cell cycle control and apoptosis resistance. To discriminate between these different roles, we used transgenic expression of survivin in the skin as a model for cell proliferation, differentiation, and apoptosis. Transgenic mice expressing survivin under the control of a keratin-14 promoter developed normally, without histologic abnormalities of the skin or hair, epidermal hyperplasia, or developmental abnormalities of basal or suprabasal epidermis. Keratinocyte proliferation assessed under basal conditions, or after ultraviolet-B (UVB) irradiation, or phorbol ester stimulation was unchanged in survivin transgenic mice. In contrast, survivin expression inhibited UVB-induced apoptosis in vitro and in vivo (i.e., sunburn cell formation), whereas it did not affect Fas-induced cell death. When crossed with p53 knockout mice, transgenic expression of survivin in a p53(+/-) background substituted for the loss of a second p53 allele and further inhibited UVB-induced apoptosis. These data provide the first in vivo evidence that survivin inhibits apoptosis and suggest that this pathway may oppose the elimination of cancerous cells by p53.
Ferroelectric Domain Wall Induced Band Gap Reduction and Charge Separation in Organometal Halide Perovskites (2015)

Organometal halide perovskites have been intensely studied in the past 5 years, inspired by their certified high photovoltaic power conversion efficiency. Some of these materials are room-temperature ferroelectrics. The presence of switchable ferroelectric domains in methylammonium lead triiodide, CH3NH3PbI3, has recently been observed via piezoresponse force microscopy. Here, we focus on the structural and electronic properties of ferroelectric domain walls in CH3NH3PbX3 (X = Cl, Br, I). We find that organometal halide perovskites can form both charged and uncharged domain walls due to the flexible orientational order of the organic molecules. The electronic band gaps for domain structures possessing 180 and 90° walls are estimated with density functional theory. It is found that the presence of charged domain walls will significantly reduce the band gap by 20-40%, while the presence of uncharged domain walls has no substantial impact on the band gap. We demonstrate that charged domain walls can serve as segregated channels for the motions of charge carriers. These results highlight the importance of ferroelectric domain walls in hybrid perovskites for photovoltaic applications and suggest a possible avenue for device optimization through domain patterning.
GDNF slows loss of motoneurons but not axonal degeneration or premature death of pmn/pmn mice (1996)

Glial cell line-derived neurotrophic factor (GDNF), a member of the TG F-beta superfamily, has been shown to be a highly potent neurotrophic factor that enhances survival of various neuronal cell types including motoneurons. To assess its therapeutic potential in treating neurodegenerative diseases such as amyotrophic lateral sclerosis, we treated mutant mice displaying motoneuron degeneration (progressive motor neuropathy; pmn) with encapsulated GDNF-secreting cells. Effects of GDNF treatment on pmn/pmn mice were compared with previous results obtained with ciliary neurotrophic factor (CNTF) [Sagot Y, Tan SA, Baetge E, Schmalbruch H, Kato AC, Aebischer P (1995) Eur J Neurosci 7:1313-1322]. In contrast to CNTF, GDNF did not increase the lifespan of pmn/pmn mice. However, GDNF significantly reduced the loss of facial motoneurons by 50%, a value similar to what was observed when CNTF was administered to the pmn/pmn mice. Surprisingly, myelinated axon counts revealed that GDNF had no effect on nerve degeneration. Therefore, despite its potential in rescuing motoneuron cell bodies, the inability of GDNF to prevent nerve degeneration in pmn/pmn mice suggests that its usefulness in the treatment of motor neuron diseases may be restricted to cotreatment with other factors that act on the nerve process.
Purification and Characterization of a Phosphoenolpyruvate Phosphatase from Brassica nigra Suspension Cells (1989)

Phosphoenolpyruvate phosphatase from Brassica nigra leaf petiole suspension cells has been purified 1700-fold to apparent homogeneity and a final specific activity of 380 micromole pyruvate produced per minute per milligram protein. Purification steps included: ammonium sulfate fractionation, S-Sepharose, chelating Sepharose, concanavalin A Sepharose, and Superose 12 chromatography. The native protein was monomeric with a molecular mass of 56 kilodaltons as estimated by analytical gel filtration. The enzyme displayed a broad pH optimum of about pH 5.6 and was relatively heat stable. Western blots of microgram quantities of the final preparation showed no cross-reactivity when probed with rabbit polyclonal antibodies prepared against either castor bean endosperm cytosolic pyruvate kinase, or sorghum leaf phosphoenolpyruvate carboxylase. The final preparation exhibited a broad substrate selectivity, showing high activity toward p-nitrophenyl phosphate, adenosine diphosphate, adenosine triphosphate, gluconate 6-phosphate, and phosphoenolpyruvate, and moderate activity toward several other organic phosphates. Phosphoenolpyruvate phosphatase possessed at least a fivefold and sixfold greater affinity and specificity constant, respectively, for phosphoenolpyruvate (apparent Michaelis constant = 50 micromolar) than for any other nonartificial substrate. The enzyme was activated 1.7-fold by 4 millimolar magnesium, but was strongly inhibited by molybdate, fluoride, zinc, copper, iron, and lead ions, as well as by orthophosphate, ascorbate, glutamate, aspartate, and various organic phosphate compounds. It is postulated that phosphoenolpyruvate phosphatase functions to bypass the adenosine diphosphate dependent pyruvate kinase reaction during extended periods of orthophosphate starvation.
An Analysis of Usage-Based Pricing Policies for Smart Products (2008)

This contribution concerns itself with the potential of Usage‐Based Pricing policies for smart products. We develop an analytical model of a supplier of machines and a customer that allows us to compare Usage‐Based Pricing to a traditional scheme with fixed prices, and to determine optimal solutions for both parties. Based on these findings, we discuss the value of Usage‐Based Pricing on an operational as well as on a strategic level. The main conclusion that can be drawn from our research is that Usage‐Based Pricing does not provide any additional value that could not also be achieved by information sharing and joint price optimization. From a more strategic perspective, however, we find that the transfer of demand risk from the customer to the supplier implied by Usage‐Based Pricing might be used as a strategic tool to attract new prospects and to enter new markets, but only to a lesser extent as a means to keep existing customers.
G-Quadruplex Hinders Translocation of BLM Helicase on DNA: A Real-Time Fluorescence Spectroscopic Unwinding Study and Comparison with Duplex Substrates (2010)

Sequences with the potential to form G-quadruplex structures are spread throughout genomic DNA. G-quadruplexes in promoter regions can play regulatory roles in gene expression. Expression of protein-encoding genes involves processing of DNA and RNA molecules at the level of transcription and translation, respectively. In order to examine how the G-quadruplex affects processing of nucleic acids, we established a real-time fluorescent assay and studied the unwinding of intramolecular G-quadruplex formed by the human telomere, ILPR and PSMA4 sequences by the BLM helicase. Through comparison with their corresponding duplex substrates, we found that the unwinding of intramolecular G-quadruplex structures was much less efficient than that of the duplexes. This result is in contrast to previous reports that multistranded intermolecular G-quadruplexes are far better substrates for the BLM and other RecQ family helicases. In addition, the unwinding efficiency varied significantly among the G-quadruplex structures, which correlated with the stability of the structures. These facts suggest that G-quadruplex has the capability to modulate the processing of DNA and RNA molecules in a stability-dependent manner and, as a consequence, may provide a mechanism to play regulatory roles in events such as gene expression.
Comparison of effects of nifedipine and nitroglycerin on large and small coronary arteries and cardiac function in conscious dogs. (1983)

The effects of nifedipine, 20 micrograms/kg, iv, and nitroglycerin, 25 micrograms/kg, iv, were compared in conscious dogs, instrumented for instantaneous and continuous measurements of coronary arterial and left ventricular (LV) diameters, arterial and LV pressures, coronary blood flow, and cardiac output. The two drugs were administered to reduce arterial pressure initially by similar amounts, by approximately 30 mm Hg. The maximal increases in large coronary arterial dimensions occurred 2-4 minutes after the initial peak reductions in arterial pressure and increases in coronary blood flow. The maximal increase in large coronary arterial cross-sectional area with nifedipine (28 +/- 2.9%) and nitroglycerin (33 +/- 5.3%) were similar. At this time, nifedipine increased coronary blood flow (114 +/- 20%) and reduced late diastolic coronary vascular resistance (-61 +/- 3.1%), whereas nitroglycerin reduced coronary blood flow (-14 +/- 1.7%) and increased late diastolic coronary vascular resistance (15 +/- 6.6%). During the time of peak large coronary arterial dilation, nifedipine reduced mean arterial pressure (-13 +/- 2.1%) and total peripheral resistance (-30 +/- 2.6%), whereas, with nitroglycerin, arterial pressure was not different from control and total peripheral resistance was significantly increased (13 +/- 1.8%). At this time, LV end-diastolic diameter was reduced with nitroglycerin (-5.6 +/- 0.4%) but unaffected by nifedipine. Thus, in the conscious dog, nitroglycerin and nifedipine induced similar effects on large coronary arteries but differing effects on resistance coronary and peripheral vessels as well as preload. Nifedipine, in contrast to nitroglycerin, induced sustained vasodilation of both coronary resistance vessels and peripheral arterioles, whereas nitroglycerin, but not nifedipine, reduced preload.
Retardation of fading and enhancement of intensity of immunofluorescence by p-phenylenediamine. (1983)

The effects of p-phenylenediamine (PD) on the extinction and intensity of fluorescence and on antigen binding in immunofluorescence microscopy was investigated. Visual and photometric comparison of tissue sections reacted sequentially with polyclonal or monoclonal antisera and appropriate fluorochromes and mounted with and without PD indicated that PD both prolonged and intensified fluorescence without evident effect on antibody binding.
A Transcriptome-proteome Integrated Network Identifies Endoplasmic Reticulum thiol oxidoreductase (ERp57) as a Hub that Mediates Bone Metastasis (2013)

Bone metastasis is the most common distant relapse in breast cancer. The identification of key proteins involved in the osteotropic phenotype would represent a major step toward the development of new prognostic markers and therapeutic improvements. The aim of this study was to characterize functional phenotypes that favor bone metastasis in human breast cancer. We used the human breast cancer cell line MDA-MB-231 and its osteotropic BO2 subclone to identify crucial proteins in bone metastatic growth. We identified 31 proteins, 15 underexpressed and 16 overexpressed, in BO2 cells compared with parental cells. We employed a network-modeling approach in which these 31 candidate proteins were prioritized with respect to their potential in metastasis formation, based on the topology of the protein-protein interaction network and differential expression. The protein-protein interaction network provided a framework to study the functional relationships between biological molecules by attributing functions to genes whose functions had not been characterized. The combination of expression profiles and protein interactions revealed an endoplasmic reticulum-thiol oxidoreductase, ERp57, functioning as a hub that retained four down-regulated nodes involved in antigen presentation associated with the human major histocompatibility complex class I molecules, including HLA-A, HLA-B, HLA-E, and HLA-F. Further analysis of the interaction network revealed an inverse correlation between ERp57 and vimentin, which influences cytoskeleton reorganization. Moreover, knockdown of ERp57 in BO2 cells confirmed its bone organ-specific prometastatic role. Altogether, ERp57 appears as a multifunctional chaperone that can regulate diverse biological processes to maintain the homeostasis of breast cancer cells and promote the development of bone metastasis.
A River Runs through It: Art Education and a River Environment (2000)

(2000). A River Runs through it: Art Education and a River Environment. Art Education: Vol. 53, Enlarging the Frame, pp. 13-18.
Silver-Catalyzed Decarboxylative Fluorination of Aliphatic Carboxylic Acids in Aqueous Solution (2012)

Although fluorinated compounds have found widespread applications in the chemical and materials industries, general and site-specific C(sp(3))-F bond formations are still a challenging task. We report here that with the catalysis of AgNO(3), various aliphatic carboxylic acids undergo efficient decarboxylative fluorination with SELECTFLUOR(®) reagent in aqueous solution, leading to the synthesis of the corresponding alkyl fluorides in satisfactory yields under mild conditions. This radical fluorination method is not only efficient and general but also chemoselective and functional-group-compatible, thus making it highly practical in the synthesis of fluorinated molecules. A mechanism involvinig Ag(III)-mediated single electron transfer followed by fluorine atom transfer is proposed for this catalytic fluorodecarboxylation.
Suppressing renal NADPH oxidase to treat diabetic nephropathy (2007)

Renal nicotinamide adenine dinucleotide phosphate reduced form (NADPH) oxidase is an important source of oxidative stress and its expression is enhanced in the glomerulus and distal tubules of diabetic nephropathy. High glucose-induced protein kinase C signalling or renal angiotensin II signalling increases the membrane translocation of cytosolic component p47phox. NADPH oxidase-derived reactive oxygen species (ROS) in the podocytes damage the glomerular basement membrane and the slit diaphragm causing proteinuria, and mesangial and glomerular endothelial NADPH oxidase increase TGF-beta and cause collagen and fibronectin accumulation. Tubular NADPH oxidase stimulated by angiotensin II or aldosterone contributes to sodium retention and to tubulointerstitial damage. Thus, inhibition of the renal renin-angiotensin II-aldosterone system with angiotensin-converting enzyme inhibitor, angiotensin II type 1 receptor blocker or selective aldosterone inhibitor indirectly suppresses NADPH oxidase reducing renal ROS, proteinuria and glomerulosclerosis. Statins are also effective in blocking the membrane translocation of Rac, especially in diabetes with hypercholesterolemia where ROS is produced by the intrinsic NADPH oxidase and by the activated macrophages. A medical herb, picrorhiza, inhibits the membrane translocation of p47phox, is a specific inhibitor of NADPH oxidase and, more so than superoxide dismutase mimetics, may be a promising strategy for the treatment of diabetic nephropathy.