gebhart/patrepeval huggingface dataset:
LIGHT, a novel ligand for lymphotoxin beta receptor and TR2/HVEM induces apoptosis and suppresses in vivo tumor formation via gene transfer. (1998)

LIGHT is a new member of tumor necrosis factor (TNF) cytokine family derived from an activated T cell cDNA library. LIGHT mRNA is highly expressed in splenocytes, activated PBL, CD8(+) tumor infiltrating lymphocytes, granulocytes, and monocytes but not in the thymus and the tumor cells examined. Introduction of LIGHT cDNA into MDA-MB-231 human breast carcinoma caused complete tumor suppression in vivo. Histological examination showed marked neutrophil infiltration and necrosis in LIGHT expressing but not in the parental or the Neo-transfected MDA-MB-231 tumors. Interferon gamma (IFNgamma) dramatically enhances LIGHT-mediated apoptosis. LIGHT protein triggers apoptosis of various tumor cells expressing both lymphotoxin beta receptor (LTbetaR) and TR2/HVEM receptors, and its cytotoxicity can be blocked specifically by addition of a LTbetaR-Fc or a TR2/HVEM-Fc fusion protein. However, LIGHT was not cytolytic to the tumor cells that express only the LTbetaR or the TR2/HVEM or hematopoietic cells examined that express only the TR2/HVEM, such as PBL, Jurkat cells, or CD8(+) TIL cells. In contrast, treatment of the activated PBL with LIGHT resulted in release of IFNgamma. Our data suggest that LIGHT triggers distinct biological responses based on the expression patterns of its receptors on the target cells. Thus, LIGHT may play a role in the immune modulation and have a potential value in cancer therapy.
A Practical Guide to International Philanthropy (2009)

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Involvement of IL-6 in mesangial proliferative glomerulonephritis. (1989)

In this study, we demonstrated that IL-6 was a possible autocrine growth factor for rat mesangial cells (MC). rIL-6 induced in vitro growth of rat MC at a concentration of 2 to 200 ng/ml and IL-6 activity was found in the supernatant of cultured rat MC. Northern blot analysis as well as in situ hybridization revealed that IL-6 mRNA was expressed in the cultured MC. Of urine samples from patients with mesangial proliferative glomerulonephritis (PGN) 50% were found to contain significant IL-6 activity (ranging from 30 to 126 pg/ml). Urine samples from other type of primary glomerular diseases such as minimal change nephrotic syndrome or healthy volunteers contained no detectable IL-6 activity. Only 2 of 27 urine samples from membranous nephropathy contained detectable amount of IL-6. Furthermore, there was some relationship between the levels of urine IL-6 and the progressive stage of PGN. Finally, by immunohistochemical staining using an anti-IL-6 mAb, it was shown that MC in the affected glomeruli of PGN patients produced IL-6, whereas MC obtained from the patients with membranous nephropathy, minimal change nephrotic syndrome or normal kidney were not found to produce IL-6. These data suggest that deregulated production of IL-6 is involved in PGN and the measurement of urine IL-6 is helpful for the differential diagnosis of PGN as well as for monitoring the progression of PGN.
MicroRNAs modulate the angiogenic properties of HUVECs (2006)

MicroRNAs (miRNAs) have recently come into focus as key posttranscriptional modulators of gene expression. In this work, we addressed whether in vitro angiogenesis is an miRNA-regulated process. We performed large-scale analysis of miRNA expression in human umbilical vein endothelial cells (HUVECs) and found that 15 highly expressed miRNAs have the receptors of angiogenic factors as putative targets. In particular, we demonstrated that miR-221 and miR-222 affect c-Kit expression and, as a consequence, the angiogenic properties of its ligand stem cell factor. Interaction between miR-222 and c-Kit is likely to be part of a complex circuit that controls the ability of endothelial cells to form new capillaries.
Kinetics of translation of γB crystallin and its circularly permutated variant in an in vitro cell‐free system: possible relations to codon distribution and protein folding (1995)

Analysis of nascent gamma B-crystallin peptides accumulating during in vitro translation in a rabbit reticulocyte lysate cell-free system was carried out. As a consequence of the irregular distribution of rare codons along the polypeptide chain of gamma B-crystallin, translation of the two-domain protein is a non-uniform process characterized by specific pauses. One of the major delays occurs during the translation of the connecting peptide between the domains. Comparing the kinetics of translation of natural gamma B-crystallin and its circularly permutated variant (with the order of the N- and C-terminal domains exchanged) reveals that the natural N-terminal domain is translated faster than the C-terminal one. Since the N-terminal domain in natural gamma B-crystallin is known to be more stable and to fold faster than the C-terminal one [E.-M. Mayr et al. (1994) J. Mol. Biol. 235, 84-88], the present data suggest that the translation rates are optimized to tune the synthesis and folding of the nascent polypeptide chain. In this connection, the pause in the linker region between the domains provides a delay allowing the correct folding of the N-terminal domain and its subsequent assistance in the stabilization of the C-terminal one.
High-performance bottom electrode organic thin-film transistors (2001)

Pentacene-based organic field effect transistors (FETs) exhibit enormous potential as active elements in a number of applications. One significant obstacle to commercial application remains: no completely lithographic process exists for forming high-performance devices. Processing constraints prevent electrodes from being lithographically patterned once the semiconductor is deposited, but depositing the electrodes before the semiconductor leads to low-performance transistors. By using self-assembled monolayers (SAMs) to change the surface energy of the metal electrodes and morphology of the pentacene subsequently grown on the electrodes, high-performance transistors may be formed using a process compatible with lithographic definition of the source and drain electrodes.
Uptake, Metabolism and Excretion of Orally and Intravenously Administered,14C- and3H-LabeledN-Acetylneuraminic Acid Mixture in the Mouse and Rat (1981)

N-Acetyl-D-[2-14C,9-3H]neuraminic acid, enzymically prepared from sodium [2-14C]-pyruvate and N-acetyl-D-[6-3H]mannosamine by N-acetylneuraminate lyase in 75% yield, was orally administered to 20 day old fasted mice. 90% of the administered neuraminic acid was absorbed from the intestine in the course of 4 h, at a rate depending on the retention time of neuraminic acid in the intestine and the mental conditions of the animals. Between 60 and 90% of the neuraminic acid was excreted in the urine without chemical alteration within the first 6 h. Four hours after administration 10% of the 3H- and 1.3% of the 14C-radioactivity were recovered in the whole blood and in liver, spleen, kidney and brain. After 3 days 0.5% of 3H- and 0.01% of 14C-radioactivity still remained in these tissues. The discrepancy of the 14C-amount relative to the 3H-quantity was accounted for by exhaled 14CO2. After intravenous injection of N-acetylneuraminic acid into rats, 90% of the radioactivity corresponding to the original substance was excreted in the urine within 10 min. Four hours after administration only 5% of the applied 3H- and 1.2% of the 14C-radioactivity were left in the blood and in liver, spleen, kidney and brain. The experiments show that neither orally nor intravenously applied N-acetylneuraminic acid can penetrate cell membranes to a large extent, with the exception of the intestine. The isotopic ratio and N-acetylneuraminate lyase activity suggest that the small amount of the neuraminic acid retained in tissues was largely cleaved by the lyase, followed by metabolism of the reaction products. It may be concluded from these observations that neuraminic acid occurring in food cannot directly be used for the biosynthesis of glycoconjugates on a large scale.
Mechanisms of collagen trimer formation. Construction and expression of a recombinant minigene in HeLa cells reveals a direct effect of prolyl hydroxylation on chain assembly of type XII collagen. (1993)

Collagen types IX, XII, and XIV are characterized by the presence of a highly conserved region comprising the most C-terminal triple helical domain (COL1, approximately 100 residues/chain) and 2 cysteines separated by 4 amino acid residues at the junction between this COL1 domain and the C-terminal non-triple helical domain (NC1). In order to better understand the functions of this conserved domain, we have constructed a recombinant minigene, comprising the sequence coding for an unrelated signal peptide and for the COL1 and NC1 domains of type XII collagen. This construct was placed under the control of the cytomegalovirus promoter and transfected into HeLa cells. The cells expressed the transfected minigene and the secreted chain, called alpha 1 (mini XII), could be detected by immunotransfer with an anti-peptide antibody recognizing an epitope found in the NC1 domain. Under conditions preventing the hydroxylation of prolyl residues (absence of ascorbate or presence of alpha alpha'-dipyridyl), interchain disulfide bridges did not form, while in the presence of ascorbate, disulfide-bonded (alpha 1 (mini XII))3 molecules were secreted. The collagenous nature and triple helical conformation of the trimeric molecule were ascertained by the differential resistances of the COL1 and NC1 domains to trypsin and collagenase digestions, respectively. Our data demonstrate that the NC1 and COL1 domains of type XII collagen contain the information necessary for trimer formation and that, contrary to the fibrillar collagen types, posttranslational modification of the triple helical domain is essential for assembly and disulfide bonding of the chains.
Acute Bronchospasm Due to Exposure to Polymethylmethacrylate Vapors During Percutaneous Vertebroplasty (2003)

Acute Bronchospasm Due to Exposure to Polymethylmethacrylate Vapors During Percutaneous VertebroplastyBrian S. Kirby, Azar Doyle and Louis A. GilulaAudio Available | Share
The cancer-testis antigens SPANX-A/C/D and CTAG2 promote breast cancer invasion (2016)

Genes that are normally biased towards expression in the testis are often induced in tumor cells. These gametogenic genes, known as cancer-testis antigens (CTAs), have been extenstively investigated as targets for immunotherapy. However, despite their frequent detection, the degree to which CTAs support neoplastic invasion is poorly understood. Here, we find that the CTA genes SPANX-A/C/D and CTAG2 are coordinately induced in breast cancer cells and regulate distinct features of invasive behavior. Our functional analysis revealed that CTAG2 interacts with Pericentrin at the centrosome and is necessary for directional migration. Conversely, SPANX-A/C/D interacts with Lamin A/C at the inner nuclear membrane and is required for the formation of actin-rich cellular protrusions that reorganize the extracellular matrix. Importantly, SPANX-A/C/D was required for breast cancer cells to spontaneously metastasize to the lung, demonstrating that CTA reactivation can be critical for invasion dependent phenotypes in vivo. Moreover, elevated SPANX-A/C/D expression in breast cancer patient tumors correlated with poor outcome. Together, our results suggest that distinct CTAs promote tumor progression by regulating complementary cellular functions that are integrated together to induce invasive behavior.
NO Contest (2004)

Information about reprints can be found online at: Reprints: document. Permissions and Rights Question and Answer about this process is available in the located, click Request Permissions in the middle column of the Web page under Services. Further information Editorial Office. Once the online version of the published article for which permission is being requested is can be obtained via RightsLink, a service of the Copyright Clearance Center, not theCirculation Researchin Requests for permissions to reproduce figures, tables, or portions of articles originally publishedPermissions: by guest on April 27,
Antisense oligonucleotides adsorbed to polyalkylcyanoacrylate nanoparticles specifically inhibit mutated Ha-ras-mediated cell proliferation and tumorigenicity in nude mice. (1994)

Ras oncogenes owe their transforming properties to single point mutations in the sequence coding for the active site of the p21 protein. These mutations lead to changes in cellular proliferation and induce tumorigenic properties. Point mutations represent a well-defined target for antisense oligonucleotides that can specifically suppress the translation of the targeted mutant mRNA. We show that the stability and cellular disponibility of antisense oligonucleotides can be markedly improved by adsorption to polyalkylcyanoacrylate nanoparticles. Nanoparticle-adsorbed antisense oligonucleotides directed to a point mutation (G-->U) in codon 12 of the Ha-ras mRNA selectively inhibited the proliferation of cells expressing the point-mutated Ha-ras gene at a concentration 100 times lower than free oligonucleotides. In addition they markedly inhibited Ha-ras-dependent tumor growth in nude mice after subcutaneous injection. These experiments show that inhibition of ras oncogenes by antisense oligonucleotides can block tumor development even though ras oncogenic activation might be an early event in tumor progression.
Determination of fluence rate and temperature distributions in the rat brain; implications for photodynamic therapy (2007)

Light and heat distributions are measured in a rat glioma model used in photodynamic therapy. A fiber delivering 632-nm light is fixed in the brain of anesthetized BDIX rats. Fluence rates are measured using calibrated isotropic probes that are positioned stereotactically. Mathematical models are then used to derive tissue optical properties, enabling calculation of fluence rate distributions for general tumor and light application geometries. The fluence rates in tumor-free brains agree well with the models based on diffusion theory and Monte Carlo simulation. In both cases, the best fit is found for absorption and reduced scattering coefficients of 0.57 and 28 cm(-1), respectively. In brains with implanted BT(4)C tumors, a discrepancy between diffusion and Monte Carlo-derived two-layer models is noted. Both models suggest that tumor tissue has higher absorption and less scattering than normal brain. Temperatures are measured by inserting thermocouples directly into tumor-free brains. A model based on diffusion theory and the bioheat equation is found to be in good agreement with the experimental data and predict a thermal penetration depth of 0.60 cm in normal rat brain. The predicted parameters can be used to estimate the fluences, fluence rates, and temperatures achieved during photodynamic therapy.
Requirements for Heterodimerization between the Orphan Nuclear Receptor Nurr1 and Retinoid X Receptors (2002)

The nuclear receptor nurr1 is a transcription factor involved in the development and maintenance of neurons synthesizing the neurotransmitter dopamine. Although the lack of nurr1 expression has dramatic consequences for these cells either in terms of differentiation or survival, the mechanisms by which nurr1 controls gene transcription still remain unclear. In the intent to understand better the modalities of action of this nuclear receptor, we have undertaken a systematic analysis of the transcriptional effects and DNA binding properties of nurr1 as a monomer or when forming dimers with the different isotypes of the retinoic X receptor (RXR). Here, we show that nurr1 acts as a gene activator independently of RXR and through an AF2-independent mechanism. In addition, heterodimerization with RXR is isotype-specific, involves multiple domains in the C-terminal region of nurr1, and requires RXR binding to DNA. RXR(alpha)-nurr1 and RXRgamma-nurr1 heterodimers bind direct repeat response elements and display no specific requirements with respect to half-site spacing. However, the retinoid responsiveness of DNA-bound heterodimers requires the reiteration of at least three nurr1 binding sites, thereby limiting retinoid-induced nurr1 transcriptional activity to specific direct response elements.
Introduction to glycobiology (2003)

1. Concepts of Glycobiology 2. N-linked glycosylation 3. Conformations of oligosaccharides 4. Strategies for analysis of glycan structures 5. O-linked glycosylation 6. Glycolipids and membrane glycosylation 7. Effects of glycosylation on protein structure and function 8. Glycoprotein trafficking in cells and organisms 9. Carbohydrate recognition in cell adhesion and signalling 10. Mechanisms of sugar recognition in animal lectins 11. Glycobiology of plants, bacteria and viruses 12. Glycosylation and disease 13. The future of glycobiology
A survey of methods for explaining black box models (2019)

In recent years, many accurate decision support systems have been constructed as black boxes, that is as systems that hide their internal logic to the user. This lack of explanation constitutes both a practical and an ethical issue. The literature reports many approaches aimed at overcoming this crucial weakness, sometimes at the cost of sacrificing accuracy for interpretability. The applications in which black box decision systems can be used are various, and each approach is typically developed to provide a solution for a specific problem and, as a consequence, it explicitly or implicitly delineates its own definition of interpretability and explanation. The aim of this article is to provide a classification of the main problems addressed in the literature with respect to the notion of explanation and the type of black box system. Given a problem definition, a black box type, and a desired explanation, this survey should help the researcher to find the proposals more useful for his own work. The proposed classification of approaches to open black box models should also be useful for putting the many research open questions in perspective.
A space-time coding modem for high-data-rate wireless communications (1998)

This paper presents the theory and practice of a new advanced modem technology suitable for high-data-rate wireless communications and presents its performance over a frequency-flat Rayleigh fading channel. The new technology is based on space-time coded modulation (STCM) with multiple transmit and/or multiple receive antennas and orthogonal pilot sequence insertion (O-PSI). In this approach, data is encoded by a space-time (ST) channel encoder and the output of the encoder is split into N streams to be simultaneously transmitted using N transmit antennas. The transmitter inserts periodic orthogonal pilot sequences in each of the simultaneously transmitted bursts. The receiver uses those pilot sequences to estimate the fading channel. When combined with an appropriately designed interpolation filter, accurate channel state information (CSI) can be estimated for the decoding process. Simulation results of the proposed modem, as applied to the IS-136 cellular standard, are presented. We present the frame error rate (FER) performance results as a function of the signal-to-noise ratio (SNR) and the maximum Doppler frequency, in the presence of timing and frequency offset errors. Simulation results show that for a 10% FER, a 32-state eight-phase-shift keyed (8-PSK) ST code with two transmit and two receive antennas can support data rates up to 55.8 kb/s on a 30-kHz channel, at an SNR of 11.7 dB and a maximum Doppler frequency of 180 Hz. Simulation results for other codes and other channel conditions are also provided. We also compare the performance of the proposed STCM scheme with delay diversity schemes and conclude that STCM can provide significant SNR improvement over simple delay diversity.
Amyotrophic Lateral Ssclerosis and Structural Defects in Cu,Zn Superoxide Dismutase (1993)

Single-site mutants in the Cu,Zn superoxide dismutase (SOD) gene (SOD1) occur in patients with the fatal neurodegenerative disorder familial amyotrophic lateral sclerosis (FALS). Complete screening of the SOD1 coding region revealed that the mutation Ala4 to Val in exon 1 was the most frequent one; mutations were identified in exons 2, 4, and 5 but not in the active site region formed by exon 3. The 2.4 A crystal structure of human SOD, along with two other SOD structures, established that all 12 observed FALS mutant sites alter conserved interactions critical to the beta-barrel fold and dimer contact, rather than catalysis. Red cells from heterozygotes had less than 50 percent normal SOD activity, consistent with a structurally defective SOD dimer. Thus, defective SOD is linked to motor neuron death and carries implications for understanding and possible treatment of FALS.
New Prodrug Activation Gene Therapy for Cancer Using Cytochrome P450 4B1 and 2-Aminoanthracene/4-Ipomeanol (1998)

Vector-mediated transfer of prodrug-activating genes provides a promising means of cancer gene therapy. In a search for more selective and more potent bioactivating enzymes for gene therapy of malignant brain tumors, the toxicity-generating capacity of the rabbit cytochrome P450 isozyme CYP4B1 was investigated. Rabbit CYP4B1, but not rat or human isozymes, efficiently converts the inert prodrugs, 2-aminoanthracene (2-AA) and 4-ipomeanol (4-IM), into highly toxic alkylating metabolites. Toxicity of these two prodrugs was evaluated in culture in parental and genetically modified rodent (9L) and human (U87) glioma cell lines stably expressing CYP4B1, and in vivo in a subcutaneous 9L tumor model in nude mice. The most sensitive CYP4B1-expressing glioma clone, 9L4B1-60, displayed an LD50 of 2.5 microM for 2-AA and 4-IM after 48 h of prodrug incubation, whereas 20 times higher prodrug concentrations did not cause any significant toxicity to control cells. Substantial killing of control tumor cells by 2-AA was achieved by co-culturing these cells with CYP4B1-expressing cells at a ratio of 100:1, and toxic metabolites could be transferred through medium. In both CYP4B1-expressing cells and co-cultured control cells, prodrug bioactivation was associated with DNA fragmentation, as assayed by fluorescent TUNEL assays and by annexin V staining. Alkaline elution of cellular DNA after exposure to 4-IM revealed extensive protein-DNA crosslinking with single-strand breakage. Growth of 9L-4B1 tumors in nude mice was inhibited by intraperitoneal injection of 4-IM with minimal side effects. Potential advantages of the CYP4B1 gene therapy paradigm include: the low concentrations of prodrug needed to kill sensitized tumor cells; low prodrug conversion by human isozymes, thus reducing toxicity to normal cells; a tumor-killing bystander effect that can occur even without cell-to-cell contact; and the utilization of lipophilic prodrugs that can penetrate the blood-brain barrier.