gebhart/patrepeval huggingface dataset:
Validation of a treatment policy for patients with prostate specific antigen failure after three‐dimensional conformal prostate radiation therapy (2003)

The current results validate the use of PSADT as an indicator of patients who may be observed expectantly or treated with AD therapy for PSA failure after 3DCRT. Prospective trials are needed to define further the optimal treatment for these patients.
Stereo R-CNN based 3D Object Detection for Autonomous Driving (2019)

We propose a 3D object detection method for autonomous driving by fully exploiting the sparse and dense, semantic and geometry information in stereo imagery. Our method, called Stereo R-CNN, extends Faster R-CNN for stereo inputs to simultaneously detect and associate object in left and right images. We add extra branches after stereo Region Proposal Network (RPN) to predict sparse keypoints, viewpoints, and object dimensions, which are combined with 2D left-right boxes to calculate a coarse 3D object bounding box. We then recover the accurate 3D bounding box by a region-based photometric alignment using left and right RoIs. Our method does not require depth input and 3D position supervision, however, outperforms all existing fully supervised image-based methods. Experiments on the challenging KITTI dataset show that our method outperforms the state-of-the-art stereo-based method by around 30% AP on both 3D detection and 3D localization tasks. Code has been released at https://github.com/HKUST-Aerial-Robotics/Stereo-RCNN.
N6,9-Disubstituted adenines: potent, selective antagonists at the A1 adenosine receptor (1991)

N6-Substituted 9-methyladenines are potent antagonists of the activation of A1 adenosine receptors. The present study assessed the effect of N6 and N-9 substituents on the binding of adenines to the A1 and A2 receptors, respectively, of rat brain cortex and striatum and also on the antagonism of the A2 receptor mediated stimulation of the adenylate cyclase of PC12 cells by N-ethyladenosine-5'-uronamide. The potency ranking of 9-substituted adenines varied directly with the hydrophobicity of the substituent: cyclopentyl greater than phenyl greater than tetrahydrofuryl greater than ethyl greater than methyl greater than 2-hydroxyethyl. The 9-substituted adenines showed little selectivity for either receptor and the R enantiomer of N6-(1-phenyl-2-propyl)-9-methyladenine was only 4-fold more potent than the S enantiomer at the A1 receptor. An N6-cyclopentyl substituent increased potency at the A1 receptor and decreased potency at the A2 receptor, resulting in selectivity for the A1 receptor of up to 39-fold. The N6-cyclopentyl group completely overshadowed the effect of the hydrophobicity of the 9-substituent. A 2-chloro substituent did not alter the potency of an N6-substituted 9-methyladenine.
Circular RNAs as Therapeutic Agents and Targets (2018)

It has recently been reported that thousands of covalently linked circular RNAs (circRNAs) are expressed from human genomes. circRNAs emerge during RNA splicing. circRNAs are circularized in a reaction termed "backsplicing," whereby the spliceosome fuses a splice donor site in a downstream exon to a splice acceptor site in an upstream exon. Although a young field of research, first studies indicate that backsplicing is not an erroneous reaction of the spliceosome. Instead, circRNAs are produced in cells with high cell-type specificity and can exert biologically meaningful and specific functions. These observations and the finding that circRNAs are stable against exonucleolytic decay are raising the question whether circRNAs may be relevant as therapeutic agents and targets. In this review, we start out with a short introduction into classification, biogenesis and general molecular mechanisms of circRNAs. We then describe reports, where manipulating circRNA abundance has been shown to have therapeutic value in animal disease models <i>in vivo</i>, with a focus on cardiovascular disease (CVD). Starting from existing approaches, we outline particular challenges and opportunities for future circRNA-based therapeutic approaches that exploit stability and molecular effector functions of native circRNAs. We end with considerations which designer functions could be engineered into artificial therapeutic circular RNAs.
Functional modulation of dendritic cells to suppress adaptive immune responses (2003)

In recent years, dendritic cells (DCs) have entered the center court of immune regulation. Dependent on their ontogeny, state of differentiation, and maturation and thereby a variable expression of membrane-bound and soluble molecules, DCs can induce immunostimulatory as well as immunoregulatory responses. This dual function has made them potential targets in vaccine development in cancer and infections as well as for the prevention and treatment of allograft rejection and autoimmune diseases. The present review is focused on the effect of immune-modulatory factors, such as cytokines and immunosuppressive drugs, and on the survival, differentiation, migration, and maturation of DC human subsets. A better understanding of DC immunobiology may lead to the development of specific therapies to prevent or dampen immune responses.
Human soluble IL-6 receptor: its detection and enhanced release by HIV infection (1992)

By using a fluorescence sandwich ELISA for the quantification of soluble human IL-6R, normal human PBMC were found to be induced to release IL-6R into culture supernatant by stimulation with PHA. Furthermore, certain promonocyte cell lines and human T-cell leukemia virus I (HTLV-I)-positive cell lines produced sIL-6R into culture supernatants constitutively. However, this was not found with HTLV-I negative T cell lines and Burkitt's B cell line. In addition, generation of supernatant IL-6R of the promonocyte cell line was significantly increased 27-fold after PMA treatment and sevenfold after infection with HIV. The released IL-6R molecules were characterized as an apparent m.w. of 50 to 55 kDa by both size-exclusion HPLC and immunoprecipitation of the soluble protein with IL-6R-specific mAb followed by SDS-PAGE analysis. Furthermore, increased levels of serum IL-6R were detected in blood donors seropositive for HIV. Moreover, the released IL-6R could bind efficiently to purified rIL-6 on solid phase and suppressed the proliferative responses of PBMC. These results suggest that the release of soluble IL-6R might be linked to regulatory functions of immune responses induced by IL-6 stimulation during normal and human retrovirus-infected cell growth and differentiation.
Modern methods in subsurface microbiology: in situ identification of microorganisms with nucleic acid probes (1997)

Like many other parts of microbial ecology, subsurface microbiology has entered the molecular age. As one example of various powerful molecular techniques, fluorescently labeled rRNA-targeted nucleic acid probes today allow an in situ identification of individual microbial cells in their natural habitats. The technique relies on the specific hybridization of the nucleic acid probes to the naturally amplified intracellular rRNA. Fluorescently labeled, rRNA-targeted oligonucleotide probes are perfect tools for many areas of microbial ecology since they can monitor specific populations in environmental samples based on constant genotypic features and not on variable phenotypic features like morphology. In case of immobilized communities like biofilms, exact spatial distributions of microorganisms can be analyzed on a micrometer scale. Recent technical improvements have increased the number of potential applications considerably. Today, better fluorescent dyes enable identification of routinely more than 50% of the cells even in oligotrophic aquatic samples in which the visualization of small cells with low numbers of ribosomes had been problematic. This compares favorably with the usually less than 1% of microorganisms which can be characterized based on cultivation-dependent methods.
CDDO-Me inhibits proliferation, induces apoptosis, down-regulates Akt, mTOR, NF-kappaB and NF-kappaB-regulated antiapoptotic and proangiogenic proteins in TRAMP prostate cancer cells. (2008)

Chemoprevention represents a promising strategy to reducing the incidence of prostate cancer which afflicts more than 240,000 males annually in the U.S. 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO) and its C-28 methyl ester (CCDO-Me) and C-28 imidazole (CDDO-Im) derivatives are synthetic oleanane triterpenoids that exhibit several-fold more potent antiinflammatory activity than naturally occurring oleanolic acid, but have not been investigated for prevention of the prostate. In order to evaluate the anticancer activity of CDDOs for prostate cancer, we have investigated the effect of synthetic oleanane triterpenoids on molecular targets relevant to the chemoprevention and treatment of prostate cancer in vitro in TRAMPC-1 cells derived from the primary tumor in the prostate of a transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse. Data demonstrate that CDDOs strongly inhibit the proliferation of TRAMPC-1 cells with a potency order of CDDO-Me>CDDO-Im>CDDO. Because CDDO-Me showed the most growth inhibitory activity it was further analyzed for the anticancer activity. CDDO-Me induced apoptosis in TRAMPC-1 cells as shown by the increased binding of annexin V-FITC and cleavage of procaspases 3, -8, and -9. It effectively inhibited the molecular targets such as p-Akt, NF-kappaB, and p-mTOR and downstream effectors of mTOR (p-S6K1, cyclin-D1, and cdk4). Further, CDDO-Me inhibited NF-kappaB-regulated antiapoptotic Bcl-2, Bcl-xL, and XIAP and proangiogenic VEGF. Taken together, these data demonstrate that CDDO-Me is potentially a potent chemopreventive agent that inhibits several molecular targets that are known to play critical roles in the development and progression of prostate cancer.
Dissemination among staphylococci of DNA sequences associated with methicillin resistance (1994)

DNA probes consisting of pUC19 containing cloned Staphylococcus aureus chromosomal fragments were constructed from two methicillin-resistant S. aureus strains with different DNA sequences 5' to mecA, the gene that mediates methicillin resistance. The probe from one strain, BMS1, contained a portion of the regulatory sequences (the terminal 641 bp of mecR1 and all of mecI) associated with the induction and repression of mecA transcription (pGO195). The second probe, from strain COL (pGO198), contained DNA not found in strain BMS1. This DNA was within the sequences added at the site of a mecR1 deletion. Genomic digests of 14 S. aureus isolates recovered between 1961 and 1969 all hybridized with pGO198. In contrast, 78% (36 of 46) of the S. aureus organisms isolated since 1988 hybridized with pGO195 but not with pGO198; the remainder hybridized with pGO198. No S. aureus isolates hybridized with both probes. Staphylococcus epidermidis digests hybridized with pGO198 (46%), pGO195 (14%), or both probes (35%); all 20 Staphylococcus haemolyticus isolates hybridized with pGO198. The restriction fragment length polymorphism patterns of all pGO198-hybridizing regions in S. aureus were identical to those in strain COL. In addition, the mecR1 deletion junction nucleotide sequences of eight S. aureus and six S. epidermidis isolates were identical. However, 21 of 23 S. epidermidis and all 20 S. haemolyticus isolates had from 5 to more than 20 additional chromosomal bands that hybridized with pGO198; none of 21 S. aureus isolates had additional hybridizing bands. These data suggest that the additional DNA responsible for the mecR1 deletion was part of a repetitive, and possibly mobile, element resident in coagulase-negative staphylococci but not in S. aureus. These data also support a hypothesis that the deletion event occurred in a coagulase-negative staphylococcus with subsequent acquisition of the interrupted sequences by S. aureus.
A new circuit-breaker integrated device for protection applications (2003)

In this paper, a new circuit-breaker integrated device for low power electronic circuit protection, based on the functional integration mode, is investigated. The influence of the physical and technological parameters of this device upon the main electrical characteristics has been analyzed using analytical models and the ATLAS software tool. The initial experimental results are presented.
Enabling high-bandwidth vehicular content distribution (2010)

We present VCD, a novel system for enabling high-bandwidth content distribution in vehicular networks. In VCD, a vehicle opportunistically communicates with nearby access points (APs) to download the content of interest. To fully take advantage of such transient contact with APs, we proactively push content to the APs that the vehicles will likely visit in the near future. In this way, vehicles can enjoy the full wireless capacity instead of being bottle-necked by the Internet connectivity, which is either slow or even unavailable. We develop a new algorithm for predicting the APs that will soon be visited by the vehicles. We then develop a replication scheme that leverages the synergy among (i) Internet connectivity (which is persistent but has limited coverage and low bandwidth), (ii) local wireless connectivity (which has high bandwidth but transient duration), (iii) vehicular relay connectivity (which has high bandwidth but high delay), and (iv) mesh connectivity among APs (which has high bandwidth but low coverage). We demonstrate the effectiveness of VCD system using trace-driven simulation and Emulab emulation based on real taxi traces. We further deploy VCD in two vehicular networks: one using 802.11b and the other using 802.11n, to demonstrate its effectiveness.
Logic devices and circuits based on giant magnetoresistance (1997)

In this paper, a new paradigm of performing logic operations is proposed. This new approach is based on the submicrometer giant magnetoresistance (GMR) effects. The key enabling features are nonvolatility, high GMR ratio, and control over the switching fields. The possible advantages of the new approach include ultrahigh density (because of the small device size), ultrahigh speed, nonvolatility, and radiation hardness. Key limitations are also identified. Several possible ways to surmount the limitations are also discussed. The proposed approach can, in principle, be applied to other material systems with similar characteristics.
Sex-lethal Interactions with Protein and RNA (1997)

Sex-lethal (Sxl) is an RNA-binding protein, containing two conserved RNA binding domains (RBDs) and a glycine-rich region, which functions as a regulator of alternative splicing in Drosophila sex determination. Previous work demonstrated that Sxl monomers interact cooperatively upon binding to target RNAs and that the cooperativity depends on the glycine-rich N terminus. Here we use band shift experiments to show that RNA binding patterns are altered when Sxl is combined with other proteins having similar glycine-rich domains, including mammalian heterogeneous nuclear (hn) RNP L and Drosophila Hrb87F (an hnRNP A/B homolog). Direct involvement of the Sxl glycine-rich region in protein interactions was verified by Far-Western analysis. Two interaction domains, the Sxl N terminus and the Sxl first RNA binding domain, were suggested by the yeast two-hybrid assay. In a systematic examination of the RNA binding properties of Sxl domains, it was found that the Sxl termini as well as the RBDs influence RNA binding specificity. Finally, selection of the Sxl optimal binding site (SELEX) confirms the importance of U-runs in the Sxl binding site and suggests a second type of non-U-run target that may be associated with RNA secondary structure.
Polymeric nano-micelles: Versatile Platform for Targeted Delivery in Cancer (2014)

Polymeric micelles are among the most promising delivery systems in nanomedicine. The growing interest in polymeric micelles as drug delivery vehicle is promoted by the advantages they offer for hydrophobic anticancer agents. The size of most polymeric micelles lies within the range 10-100 nm ensuring that they can selectively leave the circulation at tumor site via the enhanced permeability and retention effect. Their unique structure allows them to solubilize hydrophobic drugs, prolongs their circulatory half-life and eventually leads to enhanced therapeutic efficacy. In addition, they can undergo several structural modifications to further augment tumor cell uptake. In this review, we will discuss various micellar systems that have been studied in preclinical and clinical settings.
CXCR4 Chemokine Receptor Mediates Prostate Tumor Cell Adhesion through α5 and β3 Integrins (2006)

The mechanisms leading to prostate cancer metastasis are not understood completely. Although there is evidence that the CXC chemokine receptor (CXCR) 4 and its ligand CXCL12 may regulate tumor dissemination, their role in prostate cancer is controversial. We examined CXCR4 expression and functionality, and explored CXCL12-triggered adhesion of prostate tumor cells to human endothelium or to extracellular matrix proteins laminin, collagen, and fibronectin. Although little CXCR4 was expressed on LNCaP and DU-145 prostate tumor cells, CXCR4 was still active, enabling the cells to migrate toward a CXCL12 gradient. CXCL12 induced elevated adhesion to the endothelial cell monolayer and to immobilized fibronectin, laminin, and collagen. Anti-CXCR4 antibodies or CXCR4 knock out significantly impaired CXCL12-triggered tumor cell binding. The effects observed did not depend on CXCR4 surface expression level. Rather, CXCR4-mediated adhesion was established by alpha5 and beta3 integrin subunits and took place in the presence of reduced p38 and p38 phosphorylation. These data show that chemoattractive mechanisms are involved in adhesion processes of prostate cancer cells, and that binding of CXCL12 to its receptor leads to enhanced expression of alpha5 and beta3 integrins. The findings provide a link between chemokine receptor expression and integrin-triggered tumor dissemination.
Determination of the intracellular concentration of ethanol in Saccharomyces cerevisiae during fermentation (1986)

Considerable controversy exists concerning the intracellular concentration of ethanol in Saccharomyces cerevisiae during fermentation. This controversy results from problems in the measurement of the intracellular concentration of compounds like ethanol, which are being produced rapidly by metabolism and potentially diffuse rapidly from the cell. We used a new method for the determination of intracellular ethanol based on the exclusion of [14C]sorbitol to estimate the aqueous cell volume. This method avoided many of the technical problems in previous reports. Our results indicate that the extracellular concentrations of ethanol in fermenting suspensions of S. cerevisiae are less than or equal to those in the intracellular environment and do not increase to the high levels previously reported even during the most active stages of batch fermentation.
Induction of anti-HIV neutralizing antibodies by synthetic peptides. (1986)

Two synthetic peptides containing amino acid sequences analogous to the envelope glycoprotein of human T-lymphotropic virus (HTLV) type III (HTLV-III) and lymphadenopathy associated virus (LAV) were produced and used to immunize rabbits. The subsequent rabbit antisera neutralized HTLV-III infectivity in vitro. The two synthetic peptides corresponded to regions associated with the gp120 or gp41 subunits respectively, of human immunodeficiency virus (HIV). This data indicates that at least two neutralizing epitopes are present on the envelope glycoprotein of HIV and these epitopes are associated with two distinct virus envelope glycoproteins. Antisera generated against these peptides neutralized infectivity of two different isolates of HTLV-III. The data is discussed in terms of possible strategy for developing an effective vaccine against the etiologic agents of acquired immune deficiency syndrome (AIDS).
Defining the consensus sequences ofE.colipromoter elements by random selectio (1988)

The consensus sequence of E.coli promoter elements was determined by the method of random selection. A large collection of hybrid molecules was produced in which random-sequence oligonucleotides were cloned in place of a wild-type promoter element, and functional -10 and -35 E.coli promoter elements were obtained by a genetic selection involving the expression of a structural gene. The DNA sequences and relative levels of function for -10 and -35 elements were determined. The consensus sequences determined by this approach are very similar to those determined by comparing DNA sequences of naturally occurring E.coli promoters. However, no strong correlation is observed between similarity to the consensus and relative level of function. The results are considered in terms of E.coli promoter function and of the general applicability of the random selection method.
Casuarinin from the Bark ofTerminalia arjunaInduces Apoptosis and Cell Cycle Arrest in Human Breast Adenocarcinoma MCF-7 Cells (2005)

Casuarinin, a hydrolyzable tannin isolated from the bark of Terminalia arjuna L. (Combretaceae), was investigated for its antiproliferative activity in human breast adenocarcinoma MCF-7 cells. The results showed that casuarinin inhibited the proliferation of MCF-7 by blocking cell cycle progression in the G0/G1 phase and inducing apoptosis. An enzyme-linked immunosorbent assay showed that casuarinin increased the expression of p21/WAF1 concomitantly as the MCF-7 cells underwent G0/G1 arrest. An enhancement in Fas/APO-1 and its two forms of ligands, membrane-bound Fas ligand (mFasL) and soluble Fas ligand (sFasL), might be responsible for the apoptotic effect induced by casuarinin. Our study reports here for the first time that the induction of p21/WAF1 and the activity of Fas/Fas ligand apoptotic system may participate in the antiproliferative activity of casuarinin in MCF-7 cells.
Isolation of a Ribonucleoprotein Structure from Oncornaviruses (1973)

Detergent treatment releases from both avian and mammalian oncornaviruses a structure containing the viral RNA and a major arginine-rich protein, as well as reverse transcriptase activity.
Detection and characterization of a mouse alpha-spectrin cDNA clone by its expression in Escherichia coli. (1985)

A cloned segment of mouse alpha-spectrin mRNA has been identified by immunological techniques. Double-stranded cDNA derived from spleens of anemic mice was introduced into a bacterial expression vector, pUC, and transformed Escherichia coli colonies were screened by using an antiserum to erythrocyte membrane ghost proteins. Of 17 positive colonies, 2 bound antibody to mouse spectrin, and these 2 colonies contained 750-base-pair inserts that cross-hybridized. Transfer of the 750-base-pair insert to an expression vector containing the PL promoter of phage lambda produced larger amounts of peptides that were bound by antibody to mouse spectrin. The spectrin-like peptides made in E. coli elicited antibody that reacted only with the alpha-spectrin subunit of erythrocyte membranes. This clone will be useful for the study of the structure and expression of the spectrin gene, particularly in understanding the role of spectrin in human inherited hemolytic anemias.