gebhart/patrepeval huggingface dataset:
Ductal carcinoma in situ revisited (2000)

Since our review appeared in The Breast, further information from randomized studies has become available. The EORTC data have been published and are summarized in Table 1. This was a randomized trial assessing the value of radiotherapy after breast conserving surgery. The results demonstrate a significant advantage for radiotherapy both in terms of ductal carcinoma in situ (DCIS) and invasive recurrence. There was a significant excess of contralateral cancers in the irradiated group. The benefits of radiotherapy in the NSABP study was greatest in patients at high risk of recurrence. Marked/moderate comedo necrosis, solid tumour type, moderate/marked lymphoid infiltrate and multifocality were all found to be significant predictors for breast recurrence in patients treated by wide excision alone or wide local excision plus radiotherapy. Uncertain/involved margins and poor unclear grade were of borderline significance (Table 2). 1 The results relating grade to local recurrence from the EORTC study have been presented but have not been separated into groups who did or did not have radiotherapy but have not shown a relationship between degree of differentiation of DCIS and local recurrence, which is surprising (Table 3). The most recent publication from the NSABP treated patients with DCIS by wide local excision and radiotherapy and randomized them for tamoxifen, 20 mg a day for 5 years. 2 Although this study showed a significant reduction in all breast cancer events there were only significant reductions in ipsilateral invasive disease and contralateral DCIS. Surprisingly there was no apparent effect on ipsilateral DCIS and contralateral invasive cancer (Table 4). The effect of tamoxifen was also much greater in patients whose disease was incompletely excised. The role of tamoxifen in DCIS which has been widely excised remains uncertain
Importance of thioredoxin in the proteolysis of an immunoglobulin G as antigen by lysosomal Cys‐proteases (1999)

For disulphide-bonded antigens, reduction has been postulated to be a prerequisite for proteolytic antigen processing, with subsequent production of major histocompatibility complex (MHC) class II binding fragments. The murine monoclonal immunoglobulin G (IgG) CE25/B7 was used as a multimeric antigen in a human model. Native IgG is highly resistant to proteolysis and has been previously found to be partially reduced at early steps of cell processing to become a suitable substrate for endopeptidases. The role of the oxidoreductase thioredoxin (Trx) was assessed in the reduction of the IgG by cleavage of H-L and H-H disulphide bonds. Recombinant human Trx (rTrx) has been assayed in a proteolytic in vitro system on IgG using endosomal and lysosomal subcellular fractions from B lymphoblastoid cells. rTrx is required in a dose-dependent manner for development of efficient proteolysis, catalysed by thiol-dependent Cys-proteases, such as cathepsin B. We demonstrated that cathepsin B activity was stimulated by the addition of rTrx. Thus, we propose that Trx-dependent IgG proteolysis occurred, on the one hand by means of the unfolding of the IgG after disulphide reduction, becoming a substrate of lysosomal proteases, and on the other hand by Cys-proteases such as cathepsin B that are fully active upon the regeneration of their activity by hydrogen donors.
The involvement of osteopontin and its receptors in multiple myeloma cell survival, migration and invasion in the murine 5T33MM model (2005)

Multiple myeloma (MM) is a malignancy characterised by the accumulation of monoclonal plasma cells in the bone marrow. Different reports indicate the expression of CD44 variant isoforms (CD44v) by MM cells. Osteopontin (OPN), which is expressed by MM cells, is known to be a ligand for CD44v6. In this study, we investigated the role of OPN with emphasis on a functional correlation between OPN and CD44v in the 5T33MM model. Our group reported the expression of CD44v by 5T33MM cells. Using this model, we have demonstrated the secretion of OPN by 5T33MM cells. OPN affected 5T33MM cell survival by increasing proliferation and inhibiting apoptosis. OPN also stimulated 5T33MM cell migration, transendothelial migration and matrix metalloproteinase-9 activity. We confirmed the proliferative and migratory effects of OPN on human MM cells. By applying inhibiting anti-CD44v6 antibodies, we found that OPN stimulated cell proliferation by engaging this isoform. Anti-CD44v antibodies and RGD peptides both inhibited cell migration, suggesting an involvement of both, CD44v isoforms and integrins. In conclusion, OPN may act as a mediator of MM cell survival by engaging CD44v. The protein is further involved in migration and invasion of MM cells through the activation of either alphavbeta3 integrin or CD44v isoforms.
Demodex dermatitis: a retrospective analysis of clinical diagnosis and successful treatment with topical crotamiton. (2009)

Given the reported common occurrence of Demodex dermatitis in the general population, Demodex dermatitis-considered as a separate condition from rosacea and seborrheic dermatitis-was evaluated in a retrospective case analysis.
Adiponectin and Cardiovascular Disease (2009)

Obesity is strongly associated with metabolic and cardiovascular disorders. Adiponectin is an adipose-derived plasma protein that is downregulated in subjects with obesity-related disorders. Low levels of adiponectin are associated with the increased prevalence of obesity-linked cardiovascular diseases, including ischemic heart disease and peripheral artery disease. Experimental findings have shown that adiponectin has beneficial effects in the cardiovascular system by directly acting on the component cells of the heart and blood vessels. Adiponectin protects cardiovascular tissues under conditions of stress through a number of mechanisms: inhibition of pro-inflammatory and hypertrophic responses, and stimulation of endothelial cell responses. These effects of adiponectin are mainly attributed to the modulation of signaling molecules, including AMP-activated protein kinase. Thus, adiponectin could be a promising therapeutic target for cardiovascular diseases.
Depot neuroleptics in relapse prevention (1995)

Non-compliance is a major problem in the treatment of schizophrenic patients, a problem which is due to the patient's mental condition, to disturbing side effects of the medication, to a defective doctor-patient relationship, and to a general scepticism towards chemical treatment of mental symptoms. The major advantage of depot administration of neuroleptic drugs is the assurance of compliance leading to fewer relapses and rehospitalizations. Depot neuroleptics also eliminate bioavailability problems related to absorption and first pass metabolism and give a stable plasma concentration. Finally, depot neuroleptics provide a better and safer way to use the lowest effective dose principle thereby reducing the frequency of side effects, including the subjectively distressing mental side effects such as akathisia, dysphoria and neuroleptic-induced deficit syndrome. Disadvantages include delayed disappearance of potentially irreversible and unpleasant side effects after discontinuation and, for many patients, a feeling of being controlled. Administered in the proper way, with suitable information to the patient and relatives, depot neuroleptics improve the quality of antipsychotic treatment, reduce relapse frequency, stabilize the therapeutic effect and diminish the level of side effects.
Cellular Senescence Promotes Adverse Effects of Chemotherapy and Cancer Relapse (2016)

Many genotoxic chemotherapies have debilitating side effects and also induce cellular senescence in normal tissues. The senescent cells remain chronically present where they can promote local and systemic inflammation that causes or exacerbates many side effects of the chemotherapy. Cancer Discov; 7(2); 165-76. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 115.
A taxonomy of computer program security flaws (1994)

An organized record of actual flaws can be useful to computer system designers, programmers, analysts, administrators, and users. This survey provides a taxonomy for computer program security flaws, with an Appendix that documents 50 actual security flaws. These flaws have all been described previously in the open literature, but in widely separated places. For those new to the field of computer security, they provide a good introduction to the characteristics of security flaws and how they can arise. Because these flaws were not randomly selected from a valid statistical sample of such flaws, we make no strong claims concerning the likely distribution of actual security flaws within the taxonomy. However, this method of organizing security flaw data can help those who have custody of more representative samples to organize them and to focus their efforts to remove and, eventually, to prevent the introduction of security flaws.
Polymer supported enantioselective reactions. III. Protonation of lithioenamine derivatives of racemic 2-methylcyclohexanone (1982)

Asymmetric protonations, with enantioselectivities ranging to 90%, were observed in reactions of lithioenamines derived from imines of racemic 2-methylcyclohexanone and insoluble cross-linked copolymers of polystyrene and divinylbenzene substituted with (S)-2-aminoalkoxymethyl groups.
Development in vitro and in vivo of aggregated parthenogenetic bovine embryos (1995)

Mature bovine oocytes were activated with 7% ethanol followed by cytochalasin B or D treatment. Most oocytes extruded a second polar body and formed one pronucleus when treated with 7% ethanol alone [35/43 (81%)]. With ethanol followed by cytochalasin B or D, overall activation frequency was 70% (309/441), with activated oocytes containing two pronuclei. The cleavage rate was not significantly different between treatment with ethanol alone and ethanol followed by 5 micrograms mL-1 cytochalasin B, but it was significantly lower than in fertilized oocytes (P < 0.01). However, the blastocyst production rate was significantly different (P < 0.01) among the treatments. The incidence of parthenogenetic embryos with normal (diploid) complements and with chromosome anomalies (2N/4N) was 68% (17/25) and 32% (8/25) respectively, and this was not affected by cryopreservation treatment. The longitudinal diameter of aggregated-four embryos cultured in vitro was greater (P < 0.01) than aggregated-two or single embryos. One of the aggregated-four parthenogenetic embryos was further cultured in vitro and developed up to Day 27 after activation, with a diameter of 2980 microns. The aggregated-four parthenogenetic embryos were transferred to five recipients. The oestrus was prolonged in three recipients and they returned to oestrus on Day 57, 62 and 67 after the previous oestrus. These results indicate that aggregating parthenogenetic embryos can prolong their survival in vitro and in vivo.
The Transmembrane Domains of Sindbis Virus Envelope Glycoproteins Induce Cell Death (1998)

Sindbis virus, the prototype alphavirus, kills cells by inducing apoptosis. To investigate potential mechanisms by which Sindbis virus induces apoptosis, we examined whether specific viral gene products were able to induce cell death. Genes encoding the three structural proteins--capsid, the precursor E1 (6K plus E1), and the precursor E2 (P62 or E3 plus E2)--were cotransfected with a beta-galactosidase reporter plasmid in transient-transfection assays in rat prostate adenocarcinoma AT3 cells. Cell death, as determined by measuring the loss of blue cells, was observed in AT3 cells transfected with 6K plus E1 and with P62 but not in cells transfected with capsid. Deletion mutagenesis of P62 indicated that large regions of the cytoplasmic domain and extracellular domain were not essential for the induction of cell death. However, constructs containing the minimal E3 signal sequence fused to the E2 transmembrane domain and the minimal E3 signal sequence fused to the E1 transmembrane domain induced death as efficiently as full-length P62 and 6K plus E1, whereas no cell death was observed after transfection with a control construct containing the E3 signal sequence linked to the transmembrane domain of murine CD4. These data demonstrate that intracellular expression of the transmembrane domains of the Sindbis virus envelope glycoproteins can kill AT3 cells.
Simultaneous Multianalyte Detection with a Nanometer-Scale Pore (2001)

It was recently shown that naturally occurring, genetically engineered or chemically modified channels can be used to detect analytes in solution. We demonstrate here that the overall range of analytes that can be detected by single nanometer-scale pores is expanded using a potentially simpler system. Instead of attaching recognition elements to a channel, they are covalently linked to polymers that otherwise thread through a nanometer-scale pore. Because the rate of unbound polymer entering the pore is proportional to its concentration in the bulk, the binding of analyte to the polymer alters the latter's ability to thread through the pore, and the signal that results from individual polymer translocation is unique to the polymer type; the method permits multianalyte detection and quantitation. We demonstrate here that two different proteins can be simultaneously detected with this technique.
Two Intracellular Pathways Mediate Metabotropic Glutamate Receptor-Induced Ca2+Mobilization in Dopamine Neurons (2003)

Activation of metabotropic glutamate receptors (mGluRs) causes membrane hyperpolarization in midbrain dopamine neurons. This hyperpolarization results from the opening of Ca(2+)-sensitive K(+) channels, which is mediated by the release of Ca(2+) from intracellular stores. Neurotransmitter-induced mobilization of Ca(2+) is generally ascribed to the action of inositol 1,4,5-triphosphate (IP(3)) in neurons. Here we show that the mGluR-mediated Ca(2+) mobilization in dopamine neurons is caused by two intracellular second messengers: IP(3) and cyclic ADP-ribose (cADPR). Focal activation of mGluRs, attained by synaptic release of glutamate or iontophoretic application of aspartate, induced a wave of Ca(2+) that spread over a distance of approximately 50 microm through dendrites and the soma. Simultaneous inhibition of both IP(3)- and cADPR-dependent pathways with heparin and 8-NH(2)-cADPR was required to block the mGluR-induced Ca(2+) release, indicating a redundancy in the signaling mechanism. Activation of ryanodine receptors was suggested to mediate the cADPR-dependent pathway, because ruthenium red, an antagonist of ryanodine receptors, inhibited the mGluR response only when the cADPR-dependent pathway was isolated by blocking the IP(3)-dependent pathway with heparin. Finally, the mGluR-mediated hyperpolarization was shown to induce a transient pause in the spontaneous firing of dopamine neurons. These results demonstrate that an excitatory neurotransmitter glutamate uses multiple intracellular pathways to exert an inhibitory control on the excitability of dopamine neurons.
Types of Metaphor and the Cognitive Differences Reflected in Chinese and English Culture (2005)

Metaphor is not merely a rhetorical means.It is a mode of thinking that we live by.This paper presents the various types of metaphor from the point of grammar,cognitive function,syntactic structure,occurrence frequency and translation.It also analyzes the cognitive differences reflected in metaphor in Chinese and English culture.It is pointed out that the understanding of this cognitive difference plays an important role in eliminating cultural barriers and in creating an equal and new culture.
Lung Dose-Volume Parameters and the Risk of Pneumonitis for Patients Treated With Accelerated Partial-Breast Irradiation Using Three-Dimensional Conformal Radiotherapy (2009)

The risk of pneumonitis appeared related to the ILV treated. This volume can be reduced by using mixed photons and electron when possible. We recommend that the ILV 20 Gy should be lower than 3%, the ILV 10 Gy lower than 10%, and the ILV 5 Gy lower than 20% when purely coplanar techniques are used.
Constitutive expression of an ISGF2/IRF1 transgene leads to interferon-independent activation of interferon-inducible genes and resistance to virus infection (1992)

Interferon (IFN)-stimulated gene factor 2 (ISGF2) plays a role in transcription of the beta IFN (IFN-beta) gene and IFN-stimulated genes (ISGs) and may function as a central mediator of cytokine responses. Constitutive ISGF2 transgene expression resulted in substantial resistance to three RNA virus families. This phenotype was not a consequence of IFN production and may have arisen directly through ISG expression. ISGF2 acted generally as a positive transcription factor through binding sites from several genes, in the context of transient cotransfection. Constitutive transcription of the endogenous IFN-beta gene, and several genes that are normally induced by either IFN-alpha or IFN-gamma, or only by IFN-alpha, was elevated in cells that constitutively express an ISGF2 transgene. However, constitutive and virus-induced levels of IFN-beta mRNA were unaffected in such cell lines.
Differential oxygen radical susceptibility of adriamycin-sensitive and -resistant MCF-7 human breast tumor cells. (1989)

Recent evidence supports the concept that Adriamycin cytotoxicity may be mediated by drug semiquinone free radical and oxyradical generation. We tested this hypothesis further by exposing drug-sensitive (WT) and 500-fold Adriamycin-resistant MCF-7 human breast tumor cells (ADRR) to exogenous superoxide- and hydrogen peroxide-generating systems and subsequently monitored cell proliferation as a measure of cytotoxicity. The ADRR tumor cells tolerated a 4-fold greater exposure than sensitive cells to superoxide generated by the xanthine/xanthine oxidase system. Likewise, exposure to hydrogen peroxide produced by the action of glucose oxidase on glucose revealed a 4-fold diminished susceptibility of the drug-resistant cells to this reduced form of oxygen. Similar results were obtained by the direct application of hydrogen peroxide to cells. For both cell lines, cytotoxicity was dependent upon the magnitude and the duration of reactive oxygen exposure. When WT and ADRR cells were cultured under hyperoxia (95% O2:5% CO2), in order to stimulate the intracellular production of oxyradicals, proliferation was inhibited to a greater extent in the drug-sensitive cell line. Additionally, hyperoxia potentiated the cytotoxicity of Adriamycin to both sensitive and drug-resistant cells, but the effect depended upon the concentration of the drug. Under hyperoxic conditions, Adriamycin caused oxygen radical-dependent cytotoxicity to the WT tumor cells at clinically relevant drug concentrations as low as 2 to 3 nM. With ADRR tumor cells, hyperoxia increased the cytotoxicity of Adriamycin at concentrations above 5 microM. Paradoxically, both the WT and the ADRR tumor cells were equally susceptible to the cytotoxic effects of gamma irradiation. It is known that the Adriamycin-resistant MCF-7 cells greatly overexpress glutathione peroxidase and glutathione transferase activities; however, other biochemical defenses against reactive drug intermediates and oxygen radicals have been reported to be similar in the two cell lines. We have reexamined those observations in this report. The resistance of ADRR breast tumor cells to Adriamycin appears to be associated with a developed tolerance to superoxide, most likely because of a twofold increase in superoxide dismutase activity, and a decreased susceptibility to hydrogen peroxide, most likely because of 12-fold augmented selenium-dependent glutathione peroxidase activity. Acting in concert, these two enzymes would decrease the formation of hydroxyl radical from reduced molecular oxygen intermediates.(ABSTRACT TRUNCATED AT 400 WORDS)
Constitutive and inducible Saccharomyces cerevisiae promoters: evidence for two distinct molecular mechanisms. (1986)

his3 and pet56 are adjacent Saccharomyces cerevisiae genes that are transcribed in opposite directions from initiation sites that are separated by 200 base pairs. Under normal growth conditions, in which his3 and pet56 are transcribed at similar basal levels, a poly(dA-dT) sequence located between the genes serves as the upstream promoter element for both. In contrast, his3 but not pet56 transcription is induced during conditions of amino acid starvation, even though the critical regulatory site is located upstream of both respective TATA regions. Moreover, only one of the two normal his3 initiation sites is subject to induction. From genetic and biochemical evidence, I suggest that the his3-pet56 intergenic region contains constitutive and inducible promoters with different properties. In particular, two classes of TATA elements, constitutive (Tc) and regulatory (Tr), can be distinguished by their ability to respond to upstream regulatory elements, by their effects on the selection of initiation sites, and by their physical structure in nuclear chromatin. Constitutive and inducible his3 transcription is mediated by distinct promoters representing each class, whereas pet56 transcription is mediated by a constitutive promoter. Molecular mechanisms for these different kinds of S. cerevisiae promoters are proposed.
Misreading of termination codons in eukaryotes by natural nonsense suppressor tRNAs (2001)

Translational stop codon readthrough provides a regulatory mechanism of gene expression that is extensively utilised by positive-sense ssRNA viruses. The misreading of termination codons is achieved by a variety of naturally occurring suppressor tRNAs whose structure and function is the subject of this survey. All of the nonsense suppressors characterised to date (with the exception of selenocysteine tRNA) are normal cellular tRNAs that are primarily needed for reading their cognate sense codons. As a consequence, recognition of stop codons by natural suppressor tRNAs necessitates unconventional base pairings in anticodon-codon interactions. A number of intrinsic features of the suppressor tRNA contributes to the ability to read non-cognate codons. Apart from anticodon-codon affinity, the extent of base modifications within or 3' of the anticodon may up- or down-regulate the efficiency of suppression. In order to out-compete the polypeptide chain release factor an absolute prerequisite for the action of natural suppressor tRNAs is a suitable nucleotide context, preferentially at the 3' side of the suppressed stop codon. Three major types of viral readthrough sites, based on similar sequences neighbouring the leaky stop codon, can be defined. It is discussed that not only RNA viruses, but also the eukaryotic host organism might gain some profit from cellular suppressor tRNAs.
Phi-predication for light-weight if-conversion (2003)

Predicated execution can eliminate hard to predict branches and help to enable instruction level parallelism. Many current predication variants exist where the result update is conditional based upon the outcome of the guarding predicate. However, conditional writing of a register creates a naming problem for an out-of-order processor, and can stall the issuing of instructions. This problem arises from potential multiple predicated definitions reaching a use, which is unresolved until the prior predicate values are computed.In this paper we focus on a light-weight form of predication, Phi-Predication, where all predicated instructions write a result value to their register regardless of the predicate value (i.e. even if it is false). Therefore, the predicate does not guard the writing of the result register; it instead acts as a form of selection between two input registers. This eliminates the naming problem for an out-of-order processor. Our Phi-Predicated ISA is derived from the predicated features of the Multiflow ISA, with extensions to efficiently predicate complex control flow. Our compiler modifications also expand upon prior techniques to provide efficient code generation. We examine the use of Phi-Predication for an in-order and out-of-order architecture and compare its performance to using select-op and IA64 ISA predication.