gebhart/patrepeval huggingface dataset:
Bovine papilloma virus (BPV)-encoded E1 protein contains multiple activities required for BPV DNA replication. (1993)

Replication of bovine papilloma virus (BPV) DNA requires two virus-encoded proteins, E1 and E2, while all other proteins are supplied by the host cell. Here, we describe the isolation of the E1 protein and show that it is a multifunctional protein. Purified E1 protein was required for the in vitro replication of BPV origin-containing DNA by extracts of mouse cells, as reported [Yang, L., Li, R., Mohr, I. J., Clark, R. & Botchan, M. R. (1991) Nature (London) 353, 628-632]. In addition, the E1 protein cosedimented with a number of other activities including (i) DNA helicase activity, (ii) BPV origin-containing DNA-specific binding activity, (iii) DNA-dependent ATPase activity, and (iv) BPV origin-specific unwinding of superhelical DNA. The E1 protein, acting as a helicase, moved in the 3'-->5' direction, like simian virus 40 (SV40) large tumor antigen, which plays a pivotal role in SV40 DNA replication. However, unlike the SV40 large tumor antigen, the helicase activity of E1 was stimulated 5-fold by the presence of a fork structure at the junction between single-stranded and double-stranded DNA and was supported efficiently by all eight nucleoside triphosphates. The E1-catalyzed ATPase activity required the presence of single-stranded or double-stranded DNAs.
Reduced synovial membrane macrophage numbers, elam‐1 expression, and lining layer hyperplasia in psoriatic arthritis as compared with rheumatoid arthritis (1993)

Our findings demonstrate important differences in the immunohistologic features of PA and RA SM: The PA SM is more vascular, ELAM-1 expression is less intense, and fewer macrophages invade the stroma and migrate to the lining layer than in RA SM: However, the lymphocytic infiltrate in the SM of both groups is similar.
The telomerase reverse transcriptase: components and regulation (1998)

The idea that chromosomes have special terminal structures first arose as a consequence of experiments conducted by Muller, who found that treatment of Drosophila with X-rays rarely resulted in terminal deletions or inversions of the chromosomes (Muller 1938). Complementary experiments in maize by McClintock expanded upon the idea that telomeres, the physical ends of chromosomes, are required for chromosome stability, by contrasting the breakage-fusion-bridge cycle resulting from broken dicentric chromosomes with the stability of chromosomes with intact termini (McClintock 1941, 1942). With the dawn of molecular biology, telomeres in most eukaryotes are now known to be composed of short repeated G-rich sequences complexed with proteins to form a special heterochromatin-like structure. More recent experimental manipulation of chromosome termini and of the proteins that bind them have confirmed the early observations of Muller and McClintock, showing that a primary role of telomeres is to insulate the ends of chromosomes both from fusion with other ends and
Three-terminal nonlocal conductance in Majorana nanowires: Distinguishing topological and trivial in realistic systems with disorder and inhomogeneous potential (2021)

We develop a theory for the three-terminal nonlocal conductance in Majorana nanowires as existing in the superconductor-semiconductor hybrid structures in the presence of superconducting proximity, spin-orbit coupling, and Zeeman splitting. The key question addressed is whether such nonlocal conductance can decisively distinguish between trivial and topological Majorana scenarios in the presence of chemical potential inhomogeneity and random impurity disorder. We calculate the local electrical as well as nonlocal electrical and thermal conductance of the pristine nanowire (good zero-bias conductance peaks), the nanowire in the presence of quantum dots and inhomogeneous potential (bad zero-bias conductance peaks), and the nanowire in the presence of large disorder (ugly zero-bias conductance peaks). The local conductance by itself is incapable of distinguishing the trivial states from the topological states since zero-bias conductance peaks are generic in the presence of disorder and inhomogeneous potential. The nonlocal conductance, which in principle is capable of providing the bulk gap closing and reopening information at the topological quantum phase transition, is found to be far too weak in magnitude to be particularly useful in the presence of disorder and inhomogeneous potential. Therefore, we focus on the question of whether the combination of the local, nonlocal electrical, and thermal conductance can separate the good, bad, and ugly zero-bias conductance peaks in finite-length wires. Our paper aims to provide a guide to future experiments, and we conclude that a combination of all three measurements would be necessary for a decisive demonstration of topological Majorana zero modes in nanowires---positive signals corresponding to just one kind of measurements are likely to be false positives arising from disorder and inhomogeneous potential.
Random packings of spheres and spherocylinders simulated by mechanical contraction (2003)

We introduce a simulation technique for creating dense random packings of hard particles. The technique is particularly suited to handle particles of different shapes. Dense amorphous packings of spheres have been formed, which are consistent with the existing work on random sphere packings. Packings of spherocylinders have also been simulated out to the large aspect ratio of alpha=160.0. Our method packs randomly oriented spherocylinders to densities that reproduce experimental results on anisotropic powders and colloids very well. Interestingly, the highest packing density of phi=0.70 is achieved for very short spherocylinders rather than spheres. This suggests that slightly changing the shapes of the particles forming a hard sphere glass could cause it to melt. Comparisons between the equilibrium phase diagram for hard spherocylinders and the densest possible amorphous packings have interesting implications on the crystallization of spherocylinders as a function of aspect ratio.
Overexpression of Apaf-1 promotes apoptosis of untreated and paclitaxel- or etoposide-treated HL-60 cells. (1998)

Recent studies have demonstrated that Apaf-1 is the adaptor molecule which in the presence of cytosolic cytochrome c (cyt c) and dATP interacts with procaspase-9, resulting in the sequential cleavage and activity of caspase-9 and caspase-3, followed by apoptosis. In the present studies, we determined the effect of enforced overexpression of Apaf-1 on the apoptotic threshold in the human myeloid leukemia HL-60 cells. Our findings demonstrate that both transient and stable transfections resulted in a 2.5-fold higher expression of Apaf-1, which was associated with approximately a 5-fold increase in the percentage of apoptosis in the transfectants (HL-60/Apaf-1) as compared with the control HL-60/neo cells. In cells overexpressing either Bcl-2 or Bcl-xL, transient overexpression of Apaf-1 did not induce apoptosis. Stably overexpressing Apaf-1 levels significantly sensitized HL-60/Apaf-1 cells to apoptosis induced by clinically achievable concentrations of paclitaxel or etoposide (P < 0.01). This increase in paclitaxel- or etoposide-induced apoptosis of HL-60/Apaf-1 cells was not associated with any significant alterations in Bcl-2, Bcl-xL, Bax, Fas, or Fas ligand expression. It was, however, clearly associated with caspase-9 cleavage, as well as the poly(ADP-ribose) polymerase and DFF45 cleavage activity of caspase-3. Coexpression of the catalytically inactive, dominant-negative, mutant caspase-9, XIAP, or treatment with the caspase inhibitor, zVAD, significantly inhibited the increase in apoptosis of HL-60/Apaf-1 cells (P < 0.01). These data indicate that the intracellular levels of Apaf-1 is an important molecular determinant of the threshold for apoptosis induced by paclitaxel and etoposide.
Molecular assessment of surgical-resection margins of gastric cancer by mass-spectrometric imaging (2014)

Surgical resection is the main curative option for gastrointestinal cancers. The extent of cancer resection is commonly assessed during surgery by pathologic evaluation of (frozen sections of) the tissue at the resected specimen margin(s) to verify whether cancer is present. We compare this method to an alternative procedure, desorption electrospray ionization mass spectrometric imaging (DESI-MSI), for 62 banked human cancerous and normal gastric-tissue samples. In DESI-MSI, microdroplets strike the tissue sample, the resulting splash enters a mass spectrometer, and a statistical analysis, here, the Lasso method (which stands for least absolute shrinkage and selection operator and which is a multiclass logistic regression with L1 penalty), is applied to classify tissues based on the molecular information obtained directly from DESI-MSI. The methodology developed with 28 frozen training samples of clear histopathologic diagnosis showed an overall accuracy value of 98% for the 12,480 pixels evaluated in cross-validation (CV), and 97% when a completely independent set of samples was tested. By applying an additional spatial smoothing technique, the accuracy for both CV and the independent set of samples was 99% compared with histological diagnoses. To test our method for clinical use, we applied it to a total of 21 tissue-margin samples prospectively obtained from nine gastric-cancer patients. The results obtained suggest that DESI-MSI/Lasso may be valuable for routine intraoperative assessment of the specimen margins during gastric-cancer surgery.
A secure conditional access system using digital signature and encryption (2003)

A new conditional access system architecture is proposed. It uses XML digital signature and encryption to securely distribute audio, video, image, and data on the Web. It also supports payment transactions in a secure environment.
EphB2 is a Prognostic Factor in Colorectal Cancer (2005)

A receptor tyrosine kinase for ephrin ligands, EphB2 is expressed in colorectal cancer and has been proposed as a target for immunoconjugate therapy. The aim of this study was to perform a detailed histologic analysis of EphB2 expression in normal and neoplastic colorectal tissues. In addition, we sought to evaluate EphB2 expression as a prognostic factor in colorectal cancer. Expression of EphB2 was examined in normal colon (n = 28), colorectal cell lines (n = 20), colorectal adenomas (n = 148), primary cancers (n = 28), and metastases (n = 39) using immunohistochemistry. In addition, a series of primary cancers and matched normal (n = 342) with outcome data were profiled in tissue microarrays. The intensity of EphB2 expression was assessed in the entire series by immunohistochemistry, and in a subset by in situ hybridization. Overall survival and recurrence-free survival were correlated with EphB2 protein expression in retrospective subset analyses. Epithelial EphB2 expression was shown at all stages of colorectal tumorigenesis, including the base of all normal crypts, 77% of adenomas, 82% of primary cancers, and 64% of metastases. Although homogeneous expression was observed in adenomas, the pattern of staining was focal (mean 25%) in most malignant lesions. Patients whose tumor stained 2+ for EphB2 expression (versus 0/1+) exhibited significantly prolonged overall survival: mean duration of survival, 2,514 versus 1,044 days; hazard ratio, 0.45; 95% confidence interval, 0.18 to 0.95 (P = 0.035). In summary, EphB2 is expressed in normal crypts, colorectal adenomas, primary cancers, and metastases. High levels of EphB2 expression are associated with a longer mean duration of survival in colorectal cancer.
Hypotension induced by intravascular administration of nerve growth factor in the rat (1991)

1. The observation that the area postrema expresses a high level of nerve-growth-factor-receptor immunoreactivity prompted an investigation of the effects of nerve growth factor on autonomic function in the rat. 2. Bolus injection of pharmacological doses of the peptide via the femoral vein led to reproducible, dose-dependent falls in blood pressure. 3. Administration via the vertebral artery, a more direct route to the brainstem, did not appear to lower the threshold dose required to induce hypotension. Furthermore, pretreatment with hexamethonium did not inhibit the hypotensive response to nerve growth factor. 4. Administration of a second dose of nerve growth factor after recovery from the first injection produced little or no fall in blood pressure. Similarly, pretreatment with the mast cell degranulating agent, compound 48/80, rendered the animal refractory to nerve growth factor. 5. The fall in blood pressure induced by nerve growth factor was markedly attenuated by pretreatment with chlorpheniramine. 6. It is concluded that the fall in blood pressure induced by intravenous administration of pharmacological doses of nerve growth factor is mediated by vasoactive substances, particularly histamine, released from mast cells.
Numerical Modeling of Periodic Composite Media for Electromagnetic Shielding Application (2007)

This paper describes a methodology to extract effective electrical properties for periodic composite medium. The extraction algorithm is based on a periodic finite-difference time-domain (FDTD) method. The results are compared with conventional mixing theories and 3D Fourier series expansion methods. Two results show satisfactory agreement. With the extracted effective permittivity and conductivity, one can readily use these parameters to study electrical properties of composite materials with arbitrary micro-geometry and the shielding effects of using composite materials.
Abstract #1391: MiR-221&222 enhance migration and invasiveness of NSCLC and hepatocarcinoma cells by targeting PTEN tumor suppressor (2009)

Lung and liver cancer are among the most deadly type of cancer. Despite improvements in treatment over the past few decades, survival in patients remains poor. MicroRNAs (miRNA) represent a novel class of small RNAs that function as negative regulators of gene expression, deeply involved in the pathogenesis and progression of several types of cancers. In our previous work we found that miR-221 and miR-222, are markedly upregulated in TRAIL-resistant and downregulated in TRAIL-sensitive non small cell lung cancer (NSCLC) cells. Our data indicated that miR-221 and -222 modulate TRAIL sensitivity in NSCLC mainly by interfering with p27 kip1 expression and TRAIL-induced caspase machinery. Here, we show that miR-221 and miR-222, are overexpressed in aggressive NSCLC and Hepatocarcinoma cells (Calu-1 and Snu-387 cells) as compared with less invasive (H460 and Sk-Hep1 cells) and/or normal lung and liver cell lines. In all 20 different cell lines tested we found an inverse relationship between the expression of miR-221 and miR-222 and the tumor suppressor PTEN. By bioinformatic analysis, we identified one binding site for miR-221&222 in the 39 untranslated region of the tumor suppressors PTEN mRNA, and we demonstrated, by luciferase assay and by western blot, that PTEN is a direct targets of miR-221/222. Besides modulating AKT pathway, and thus cell survival, PTEN down-regulation enhances invasiveness and cellular migration as assessed by migration and invasion assays,through the activation,evidenced by western blot, of the ERKs pathway. Moreover, by MTT, Annexin-FITC assay and caspase 3/7 activity, we found that miR-221&222 overexpression induce cell survival and TRAIL resistance both in NSCLC and Hepatocarcinoma cells through the down-regulation of PTEN protein and activation of Akt pathway. In vitro and in vivo functional studies such as the use of anti-miRs oligonucleotides, immunohistochemistry and in situ hybridization on 20 primary lung and liver tumor specimens, suggest that miR-221/222 can be regarded as oncogenes in those types of cancer, because they directly target and down-regulate the tumor suppressor PTEN. Furthermore, their overexpression might be an important factor contributing to TRAIL resistance and to invasiveness of NSCLC and Hepatocarcinoma cells. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1391.
In Vitro and in Vivo Anticancer Activity of a Synthetic Glycolipid as Toll-like Receptor 4 (TLR4) Activator (2011)

Activation of Toll-like receptor 4 (TLR4) triggers the innate immune response and leads to the induction of adaptive immunity. TLR4 agonists are known to function as immunostimulants and exhibit promising therapeutic potential for cancer immunotherapy. We have previously developed a synthetic serine-based glycolipid (designated as CCL-34) that can activate TLR4-dependent signaling pathways. In this study, the anticancer immunity of CCL-34 was further demonstrated. CCL-34-activated macrophages induced cancer cell death via the apoptotic pathway, and this cytotoxicity was significantly inhibited by NG-monomethyl-L-arginine (an inducible NOS inhibitor). Notably, conditioned medium collected from CCL-34-treated splenocytes also induced cytotoxicity toward cancer cells. Furthermore, CCL-34 treatment suppressed tumor growth and increased the survival rate in TLR4-functional C3H/HeN mice but not in TLR4-defective C3H/HeJ mice. Increased apoptosis, the induction of cytokines (IFN-γ and IL-12) and chemokines (CXCL9 and CXCL10), and the elevation of leukocyte markers (CD11b, CD11c, CD4, and CD8) were detected at tumor sites in C3H/HeN mice but not in C3H/HeJ mice. Structure-and-activity relationship analysis of CCL-34 and its structural analogs revealed that a sugar moiety is essential for its activity. However, the substitution of the galactose in CCL-34 with glucose or fucose did not reduce its activity. Altogether, this study reveals the anticancer activity of a new synthetic TLR4 agonist and broadens the molecular basis of TLR4-activating glycolipids.
The challenge of spoken language systems: Research directions for the nineties (1995)

A spoken language system combines speech recognition, natural language processing and human interface technology. It functions by recognizing the person's words, interpreting the sequence of words to obtain a meaning in terms of the application, and providing an appropriate response back to the user. Potential applications of spoken language systems range from simple tasks, such as retrieving information from an existing database (traffic reports, airline schedules), to interactive problem solving tasks involving complex planning and reasoning (travel planning, traffic routing), to support for multilingual interactions. We examine eight key areas in which basic research is needed to produce spoken language systems: (1) robust speech recognition; (2) automatic training and adaptation; (3) spontaneous speech; (4) dialogue models; (5) natural language response generation; (6) speech synthesis and speech generation; (7) multilingual systems; and (8) interactive multimodal systems. In each area, we identify key research challenges, the infrastructure needed to support research, and the expected benefits. We conclude by reviewing the need for multidisciplinary research, for development of shared corpora and related resources, for computational support and far rapid communication among researchers. The successful development of this technology will increase accessibility of computers to a wide range of users, will facilitate multinational communication and trade, and will create new research specialties and jobs in this rapidly expanding area.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Post‐surgical recurrent varicocele: efficacy of internal spermatic venography and steel‐coil embolization (1996)

Objective To delineate the venographic anatomy of the varicoceles which recur following conventional inguinal varicocele ligation and to determine the therapeutic efficacy of steel‐coil embolization as assessed by improvements in seminal parameters and paternity. Patients and methods Thirty‐nine patients with post‐surgical recurrent varicoceles underwent bilateral internal spermatic venography approached through the right femoral vein. The collateral venous channels were identified and occluded using appropriate sizes of steel coils. Results The procedure was technically successful in 33 patients (85%). Analysis of the 33 venograms showed a unilateral left‐sided recurrent varicocele in 28 patients (85%) and bilateral recurrent varicoceles in five patients (15%). The mid and lower parallel collateral channels were observed in 27 patients (82%). The recurrences were treated easily with stainless steel‐coil embolization. Five patients were lost to follow‐up. Of the remaining 28 patients the sperm count and motility became normal in 16 (57%); only the motility improved in three patients (10%) while in nine patients (33%) there were no changes in either of the seminal parameters. Five patients achieved paternity. Conclusions Internal spermatic venography allowed a precise anatomical definition of the recurrent varicocele and the use of steel‐coil embolization provided satisfactory improvements in sperm quality and paternity.
Mechanisms of the Apoptotic and Necrotic Actions of Trimethyltin in Cerebellar Granule Cells (2001)

In evaluating mechanisms of trimethyltin (TMT)-initiated neuronal damage, the present study focused on involvement of reactive oxygen species, protein kinase C (PKC), and glutamate receptors. Exposure of cerebellar granule cells to TMT (0.01-0.1 microM) produced primarily apoptosis, but higher concentrations were associated with cellular lactate dehydrogenase efflux and necrosis. TMT increased generation of cellular reactive oxygen species, which was inhibited by either L-NAME (inhibitor of nitric oxide synthase, NOS) or catalase, indicating that both NO and H(2)O(2) are formed on TMT exposure. Since chelerythrine (selective PKC inhibitor) also inhibited oxidative species generation, PKC appears to play a significant role in TMT-induced oxidative stress. The metabotropic glutamate receptor antagonist, MCPG, (but not MK-801) prevented oxidative species generation, indicating significant involvement of metabotropic receptors (but not NMDA receptors) in TMT-induced oxidative stress. NOS involvement in the action of TMT was confirmed through measurement of nitrite, which increased concentration dependently. Nitrite accumulation was blocked by L-NAME, chelerythrine, or MCPG, showing that NO is generated by TMT and that associated changes in NOS are regulated by a PKC-mediated mechanism. Oxidative damage by TMT was demonstrated by detection of elevated malondialdehyde levels. It was concluded that low concentrations of TMT (0.01-0.1 microM) cause apoptotic cell death in which oxidative signaling is an important event. Higher concentrations of TMT initiate necrotic death, which involves both an oxidative and a non-oxidative component. TMT-induced necrosis but not apoptosis in granule cells is mediated by glutamate receptors.