gebhart/patrepeval huggingface dataset:
Apoptosis and cancer chemotherapy (1994)

The major disseminated cancers remain stubbornly resistant to systemic therapy. Drug-resistant tumours include both slow and fast growing types, with the carcinomas constituting the major problem. Strategies for drug discovery have, in the past, been focused on attempts to design antiproliferative agents, largely targeted to interfere with DNA integrity and replication. The malignant phenotype might be characterized by the emergence of cell populations with a greater survival potential: a lower proclivity to undergo apoptosis. This idea provides a possible explanation of the genesis and progression of cancer and of the inherent resistance of tumour cells to engage apoptosis. Work is described which identifies the molecular basis for differences in the survival potential of stem cells in the crypts of the colon and small intestine. The advantageous survival of colonic stem cells, provided by expression of bcl-2 and a muted p53 response to DNA damage, allows damaged cells to survive. Continued expression of bcl-2 renders tumour cells resistant to drug-induced DNA damage by a mechanism different from classical mechanisms of drug resistance. The attenuation of cell survival is described as a key component in strategies for the drug treatment of disseminated cancers.
Anti-double-stranded DNA antibodies and immunostimulatory plasmid DNA in combination mimic the endogenous IFN-alpha inducer in systemic lupus erythematosus. (1999)

Patients with systemic lupus erythematosus (SLE) have increased blood levels of IFN-alpha, which correlate to disease activity. We previously identified an IFN-alpha-inducing factor (IIF) in the blood of SLE patients that activated the natural IFN-alpha-producing cells in cultures of normal PBMC. The SLE-IIF contained DNA and IgG, possibly as small immune complexes. In our study, we demonstrated that SLE-IIF correlated to the presence of anti-dsDNA Abs in patients and contained anti-dsDNA Abs as an essential component. Purified anti-DNA Abs or SLE-IgG caused only a weak IFN-alpha production in cultures of normal PBMC in the presence of costimulatory IFN-alpha2b. However, they converted the plasmid pcDNA3, which itself induced no IFN-alpha production in PBMC, into an efficient IFN-alpha inducer. A human monoclonal anti-ss/dsDNA Ab had the same effect. This IFN-alpha-inducing activity of the plasmid was abolished by methylation, suggesting that unmethylated CpG DNA motifs were important. Like IIF in SLE serum, the combination of SLE-IgG and pcDNA3 appeared to stimulate IFN-alpha production in natural IFN-alpha-producing cells, a unique cell population resembling immature dendritic cells. The IFN-alpha production was greatly enhanced by IFN-alpha2b and IFN-beta, and for SLE-IIF it was also enhanced by GM-CSF but inhibited by IL-10. We have therefore identified a new function of DNA-anti-DNA Ab complexes, IFN-alpha induction, that might be important in the pathogenesis of SLE.
Dopamine as a Prolactin (PRL) Inhibitor (2001)

Dopamine is a small and relatively simple molecule that fulfills diverse functions. Within the brain, it acts as a classical neurotransmitter whose attenuation or overactivity can result in disorders such as Parkinson's disease and schizophrenia. Major advances in the cloning and characterization of biosynthetic enzymes, transporters, and receptors have increased our knowledge regarding the metabolism, release, reuptake, and mechanism of action of dopamine. Dopamine reaches the pituitary via hypophysial portal blood from several hypothalamic nerve tracts that are regulated by PRL itself, estrogens, and several neuropeptides and neurotransmitters. Dopamine binds to type-2 dopamine receptors that are functionally linked to membrane channels and G proteins and suppresses the high intrinsic secretory activity of the pituitary lactotrophs. In addition to inhibiting PRL release by controlling calcium fluxes, dopamine activates several interacting intracellular signaling pathways and suppresses PRL gene expression and lactotroph proliferation. Thus, PRL homeostasis should be viewed in the context of a fine balance between the action of dopamine as an inhibitor and the many hypothalamic, systemic, and local factors acting as stimulators, none of which has yet emerged as a primary PRL releasing factor. The generation of transgenic animals with overexpressed or mutated genes expanded our understanding of dopamine-PRL interactions and the physiological consequences of their perturbations. PRL release in humans, which differs in many respects from that in laboratory animals, is affected by several drugs used in clinical practice. Hyperprolactinemia is a major neuroendocrine-related cause of reproductive disturbances in both men and women. The treatment of hyperprolactinemia has greatly benefited from the generation of progressively more effective and selective dopaminergic drugs.
Trabecular meshworks in the sinusoidal endothelial cells of the golden hamster liver: a freeze-fracture study. (1994)

Trabecular meshworks (TMs) in the sinusoidal endothelial cells of fasted-refed golden hamster liver were studied in thin sections and in freeze-fracture replicas. TM was a plasmalemma-attached reticulum of anastomosing trabeculae composed of the plasmalemma and cytosol. The surface of TM appeared as a sieve on the plasmalemma. The floor of TM appeared as a depression with snapped trabeculae on the P-face plasmalemma and as a mound, or inverted depression, with pits containing snapped trabeculae on the E-face plasmalemma. Faint ridges were seen connecting some trabeculae on the P-face plasmalemma, whereas furrows lined with intramembranous particles (IMPs) were seen spanning some trabeculae on the E-face plasmalemma. Circles of lined IMPs (IMP-circles) were seen on the E-face plasmalemma, either alone or in association with TMs. Plasmalemmal invaginations were often centered in IMP-circles and were sometimes seen in a cluster. TMs were often blended with the sieve plates.
Simultaneous visualization of seven different DNA probes by in situ hybridization using combinatorial fluorescence and digital imaging microscopy. (1992)

Combinatorial labeling of probes (i.e., with two or more different reporters) increases the number of target sequences that can be detected simultaneously by fluorescence in situ hybridization. We have used an epifluorescence microscope equipped with a digital imaging camera and computer software for pseudocoloring and merging images to distinguish up to seven different probes using only three fluorochromes. Chromosome-specific centromere repeat clones and chromosome-specific "composite" probe sets were generated by PCR in which different mixtures of modified nucleotides, including fluorescein-conjugated dUTP, were incorporated. Cosmid clones were labeled similarly by nick-translation. The technique has been used to delineate the centromeres of seven different human chromosomes, on both 4',6-diamidino-2-phenylindole-stained metaphase spreads and interphase nuclei, to map six cosmid clones in a single hybridization experiment and to detect chromosome translocations by chromosome painting. Multiparameter hybridization analysis should facilitate molecular cytogenetics, probe-based pathogen diagnosis, and gene mapping studies.
Minimally Cultured or Selected Autologous Tumor-infiltrating Lymphocytes After a Lympho-depleting Chemotherapy Regimen in Metastatic Melanoma Patients (2009)

Adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TIL) and high-dose interleukin-2 (IL-2), after nonmyeloablative chemotherapy, has been shown to result in tumor regression in half of refractory metastatic melanoma patients. In the present study, we describe 2 separate clinical protocols. Twelve patients were treated with "Selected"-TIL, as previously reported and 8 patients with the modified version of "Young"-TIL. Selected-TIL protocol required the establishment of multiple T-cell cultures from 1 patient and in vitro selection of cultures secreting interferon-gamma upon antigenic stimulation. In contrast, Young-TIL are minimally cultured T cells with superior in vitro features that do not require further selection. Two of 12 Selected-TIL patients experienced objective clinical responses (1 complete response, 1 partial response). Out of 8 treated Young-TIL patients, 1 experienced complete response, 2 partial response, and 4 patients had disease stabilization. Twenty-one of 33 enrolled Selected-TIL patients were excluded from the protocol, mainly as cultures failed the interferon-gamma selection criteria or due to clinical deterioration, compared with only 3 Young-TIL patients. Expected bone marrow suppression and high-dose IL-2 toxicity were transient. There was no treatment-related mortality. This study vindicates the feasibility and effectiveness of TIL technology and calls for further efforts to implement and enhance this modality. The use of minimally cultured, unselected Young-TIL enables the treatment of most enrolled patients. Although the cohort of Young-TIL patients treated so far is rather small and the follow-up short, the response rate is encouraging.
The fundamental basis of inflammatory bowel disease (2007)

Two broad hypotheses have arisen regarding the fundamental nature of the pathogenesis of inflammatory bowel diseases (IBDs, which include ulcerative colitis and Crohn disease). The first contends that primary dysregulation of the mucosal immune system leads to excessive immunologic responses to normal microflora. The second suggests that changes in the composition of gut microflora and/or deranged epithelial barrier function elicits pathologic responses from the normal mucosal immune system. Here we examine these hypotheses and conclude that IBD is indeed characterized by an abnormal mucosal immune response but that microbial factors and epithelial cell abnormalities can facilitate this response.
Nanostructured Ultrathin Films of Water-Soluble Sexithiophene Bolaform Amphiphiles Prepared by Layer-by-Layer Self-Assembly (2002)

Sexithiophene bolaform amphiphiles with pendant cationic end groups (6TN) were synthesized and alternating multilayers of 6TN and poly(styrenesulfonate) (PSS) were successfully prepared by the layer-by-layer self-assembly deposition technique. The aggregation properties and layer ordering were investigated in view of their potential application for organic field effect transistors (FETs). 6TN ultrathin films were prepared from aqueous solution and water/tetrahydrofuran (THF) (70/30 v/v) mixtures. The amphiphiles showed fine aggregates in water, probably due to the intermolecular interactions of the hydrophobic sexithiophene group. Deaggregation was observed when 30 vol % THF was added, which is a better solvent for the hydrophobic portion of the molecule. A stepwise and regular deposition of 6TN/PSS multilayer in both water and water/THF (70/30) was confirmed by UV−visible spectroscopy, ellipsometry, and surface plasmon spectroscopy. A lower energy vibronic structure was observed with the UV−vis spectra on multilayers prepared with 6TN in water and water/THF (70/30). This is indicative of aggregates of 6TN in water directly adsorbed on the substrate. In the case of 6TN in a water/THF (70/30) mixture, well-stacked aggregates were only formed during adsorption to the surface. These observations were also confirmed from the atomic force microscopic (AFM) images, distinguishing the two types of aggregation and adsorption profiles. The difference in layer thickness between the two systems is most likely due to the reduced surface coverage in the 30% THF system. Polarized UV−vis spectra indicated that the rigid sexithiophene group of 6TN is oriented more parallel to the substrate than perpendicular.
Stargazin and Other Transmembrane AMPA Receptor Regulating Proteins Interact with Synaptic Scaffolding Protein MAGI-2 in Brain (2006)

The spatial coordination of neurotransmitter receptors with other postsynaptic signaling and structural molecules is regulated by a diverse array of cell-specific scaffolding proteins. The synaptic trafficking of AMPA receptors by the stargazin protein in some neurons, for example, depends on specific interactions between the C terminus of stargazin and the PDZ [postsynaptic density-95 (PSD-95)/Discs large/zona occludens-1] domains of membrane-associated guanylate kinase scaffolding proteins PSD-93 or PSD-95. Stargazin [Cacng2 (Ca2+ channel gamma2 subunit)] is one of four closely related proteins recently categorized as transmembrane AMPA receptor regulating proteins (TARPs) that appear to share similar functions but exhibit distinct expression patterns in the CNS. We used yeast two-hybrid screening to identify MAGI-2 (membrane associated guanylate kinase, WW and PDZ domain containing 2) as a novel candidate interactor with the cytoplasmic C termini of the TARPs. MAGI-2 [also known as S-SCAM (synaptic scaffolding molecule)] is a multi-PDZ domain scaffolding protein that interacts with several different ligands in brain, including PTEN (phosphatase and tensin homolog), dasm1 (dendrite arborization and synapse maturation 1), dendrin, axin, beta- and delta-catenin, neuroligin, hyperpolarization-activated cation channels, beta1-adrenergic receptors, and NMDA receptors. We confirmed that MAGI-2 coimmunoprecipitated with stargazin in vivo from mouse cerebral cortex and used in vitro assays to localize the interaction to the C-terminal -TTPV amino acid motif of stargazin and the PDZ1, PDZ3, and PDZ5 domains of MAGI-2. Expression of stargazin recruited MAGI-2 to cell membranes and cell-cell contact sites in transfected HEK-293T cells dependent on the presence of the stargazin -TTPV motif. These experiments identify MAGI-2 as a strong candidate for linking TARP/AMPA receptor complexes to a wide range of other postsynaptic molecules and pathways and advance our knowledge of protein interactions at mammalian CNS synapses.
Promoter-hypermethylation is causing functional relevant downregulation of methylthioadenosine phosphorylase ( MTAP ) expression in hepatocellular carcinoma (2005)

The methylthioadenosine phosphorylase (MTAP) gene is localized in the chromosomal region 9p21. Here, frequently homozygous deletions occur in several kinds of cancer associated with the loss of tumour suppressor genes as p16 and p15. The aim of this study was to analyse MTAP expression in hepatocellular carcinoma (HCC) and to get an insight into the regulation and functional role of MTAP in hepatocancerogenesis. Compared with primary human hepatocytes MTAP expression was markedly downregulated in three different HCC cell lines as determined by real-time PCR and western blotting. This was not due to genomic losses or mutations but to promoter-hypermethylation. Reduced MTAP-expression was confirmed in vivo in HCC compared with non-cancerous liver tissue on both mRNA and protein levels. To study the functional relevance of the downregulated MTAP expression in HCC, MTAP expression was re-induced in HCC cell lines by stable transfection. In these MTAP re-expressing cell clones the invasive potential was strongly reduced, whereas no effects on cell proliferation were observed in comparison with mock transfected cell clones. Furthermore, in MTAP re-expressing cells interferon (IFN)-alpha and IFN-gamma induced a significantly stronger inhibition of cell proliferation than in mock transfected cells. In conclusion, our results suggest a functional role of MTAP inactivation in HCC development and invasiveness. Furthermore, in the light of a recent report revealing an association between MTAP activity and IFN sensitivity, our findings may have clinical significance for therapeutic strategies.
Multicarrier transmission technique in cellular mobile communications systems (2002)

The well known orthogonal frequency division multiplexing (OFDM) multicarrier transmission technique is tailored for a broadband cellular mobile communications system. A performance analysis in multipath fading radio channels is presented and the average bit error rate (BER) is calculated in dependence of the signal-to-noise ratio for bad urban and hilly terrain channel models, following the COST-207 report. Pros and cons for OFDM and code division multiple access (CDMA) techniques are discussed on the basis system robustness, receiver complexity and bandwidth efficiency.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A bacterial haloalkane dehalogenase gene as a negative selectable marker in Arabidopsis (1999)

The dhlA gene of Xanthobacter autotrophicus GJ10 encodes a dehalogenase which hydrolyzes dihalo- alkanes, such as 1, 2-dichloroethane (DCE), to a halogenated alcohol and an inorganic halide (Janssen et al. 1994, Annu. Rev. Microbiol. 48, 163-191). In Xanthobacter, these alcohols are further catabolized by alcohol and aldehyde dehydrogenase activities, and by the product of the dhlB gene to a second halide and a hydroxyacid. The intermediate halogenated alcohols and, in particular, the aldehydes are more toxic than the haloalkane substrates or the pathway products. We show here that plants, including Arabidopsis, tobacco, oil seed rape and rice, do not express detectable haloalkane dehalogenase activities, and that wild-type Arabidopsis grows in the presence of DCE. In contrast, DCE applied as a volatile can be used to select on plates or in soil transgenic Arabidopsis which express dhlA. The dhlA marker therefore provides haloalkane dehalogenase reporter activity and substrate dependent negative selection in transgenic plants.
Learning openCV: computer vision with the openCV library (2008)

Learning OpenCV puts you right in the middle of the rapidly expanding field of computer vision. Written by the creators of OpenCV, the widely used free open-source library, this book introduces you to computer vision and demonstrates how you can quickly build applications that enable computers to see" and make decisions based on the data. With this book, any developer or hobbyist can get up and running with the framework quickly, whether it's to build simple or sophisticated vision applications
Discovery, regulation, and action of the major apoptotic nucleases DFF40/CAD and endonuclease G (2005)

Abstract Toward the end of the 20th and beginning of the 21st centuries, clever in vitro biochemical complementation experiments and genetic screens from the laboratories of Xiaodong Wang, Shigekazu Nagata, and Ding Xue led to the discovery of two major apoptotic nucleases, termed DNA fragmentation factor (DFF) or caspase‐activated DNase (CAD) and endonuclease G (Endo G). Both endonucleases attack chromatin to yield 3′‐hydroxyl groups and 5′‐phosphate residues, first at the level of 50–300 kb cleavage products and next at the level of internucleosomal DNA fragmentation, but these nucleases possess completely different cellular locations in normal cells and are regulated in vastly different ways. In non‐apoptotic cells, DFF exists in the nucleus as a heterodimer, composed of a 45 kD chaperone and inhibitor subunit (DFF45) [also called inhibitor of CAD (ICAD‐L)] and a 40 kD latent nuclease subunit (DFF40/CAD). Apoptotic activation of caspase‐3 or ‐7 results in the cleavage of DFF45/ICAD and release of active DFF40/CAD nuclease. DFF40's nuclease activity is further activated by specific chromosomal proteins, such as histone H1, HMGB1/2, and topoisomerase II. DFF is regulated by multiple pre‐ and post‐activation fail‐safe steps, which include the requirements for DFF45/ICAD, Hsp70, and Hsp40 proteins to mediate appropriate folding during translation to generate a potentially activatable nuclease, and the synthesis in stoichiometric excess of the inhibitors (DFF45/35; ICAD‐S/L). By contrast, Endo G resides in the mitochondrial intermembrane space in normal cells, and is released into the nucleus upon apoptotic disruption of mitochondrial membrane permeability in association with co‐activators such as apoptosis‐inducing factor (AIF). Understanding further regulatory check‐points involved in safeguarding non‐apoptotic cells against accidental activation of these nucleases remain as future challenges, as well as designing ways to selectively activate these nucleases in tumor cells. © 2005 Wiley‐Liss, Inc.
Protection from rabies by a vaccinia virus recombinant containing the rabies virus glycoprotein gene. (1984)

Inoculation of rabbits and mice with a vaccinia-rabies glycoprotein recombinant (V-RG) virus resulted in rapid induction of high concentrations of rabies virus-neutralizing antibodies and protection from severe intracerebral challenge with several strains of rabies virus. Protection from virus challenge also was achieved against the rabies-related Duvenhage virus but not against the Mokola virus. Effective immunization by V-RG depended on the expression of a rabies glycoprotein that registered proline rather than leucine as the eighth amino acid from its NH2 terminus (V-RGpro8). A minimum dose required for effective immunization of mice was 10(4) plaque-forming units of V-RGpro8 virus. beta-propiolactone-inactivated preparations of V-RGpro8 virus also induced high levels of rabies virus-neutralizing antibody and protected mice against intracerebral challenge with street rabies virus. V-RGpro8 virus was highly effective in priming mice to generate a secondary rabies virus-specific cytotoxic T-lymphocyte response following culture of lymphocytes with either ERA or PM strains of rabies virus.
HPLC Isolation and Mass Spectrometric Characterization of Two Isomers of Thymine Glycols in Oligodeoxynucleotides (2002)

Thymine glycol, or 5,6-dihydroxy-5,6-dihydrothymine, is the major oxidation product of thymine. Herein we report the isolation of both the (5S, 6R) and (5R, 6S) isomers of cis thymine glycols from several synthetic oligodeoxynucleotides (ODNs) upon oxidation with osmium tetraoxide. Our results show that tandem mass spectrometry can determine the sites of thymine glycol in ODNs by producing characteristic fragment ions, [a - 143] and its complementary w ions at the modification site. We further demonstrate that the [M + H]+ and [M + Na]+ ions of the two cis stereoisomers of thymine glycol in the dinucleotides, which are extricated from the ODNs by nuclease P1, gave distinctive product-ion spectra.
Histologic findings after in vivo placement of small intestine submucosal vascular grafts and saphenous vein grafts in the carotid artery in dogs. (1992)

A small caliber vascular graft from porcine small intestine submucosa (SIS) was implanted in a canine carotid artery (n = 24) and compared with an autogenous saphenous vein graft that was implanted in the contralateral carotid artery. In this study, four grafts were evaluated at the following times after surgery: 2, 7, 14, 28, 90, and 180 days. One SIS graft thrombosed at 2 days, two SIS and two saphenous vein grafts were thrombosed at 90 days, and one SIS and one saphenous vein graft were thrombosed at 180 days. At 2 days after implant, the luminal surface of the SIS graft was covered by a thin (30 mu) fibrin meshwork. By 14 days after surgery, endothelial cells on the fibrin meshwork were staining for FVIII-related antigen. Smooth muscle cells were observed in the new intima (fibrin meshwork) by 28 days. At 90 days, both types of graft had arterialized with an intima covered by endothelium, a smooth muscle media, and marked adventitial fibrosis. Similar histology was observed at 180 days. These results indicate that this SIS graft was similar to saphenous vein graft in the dog.