gebhart/patrepeval huggingface dataset:
Prognostic Factors for Carcinoma of the Prostate (1999)

Prognostic factors for prostatic carcinoma should be significant, independent and clinically important. They should be of practical use, and their determination should be affordable in everyday practice. Prognostic factors may be grouped into patient-related, tumor-related and treatment-related. They should meet certain requirements, such as possession of a clear biological significance, an adequate sample size (possibly more than 150 patients), no patient population bias, an adequate statistical test, such as Cox regression analysis, as well as optimized cut-off values and reproducibility. From a pathologist's view, prognostic factors with established values are grade, margin involvement, capsular penetration, seminal vesical involvement, metastases and invasion of fat in needle biopsies. In contrast to this, factors with little value are, among others, zone location or nuclear shape. If these guidelines for assessment of prognostic factors are not met, the prognostic factors grow exponentially, as an individual patient can only belong to one prognostic group. If one considers all three categories of prognostic factors together, the clinical stage matters most despite all uncertainties. The same holds true for grading; particularly, the well-differentiated grades on biopsy cores have the drawback of being reflected in the specimen only infrequently. The use of biomarkers to give a better prognostic information is also disappointing, as only PSA and PAP have a reliable value among 28 biomarkers. It is of note that new biomarkers are continuously being discovered and examined, such as cyclin A or D. Due to these deficiencies in all three categories of prognostic factors for prostatic carcinoma, prognostic indices in the form of nomograms were constructed. But, if these indices are employed to answer the most important question at the time of diagnosis, i.e., 'is this man a candidate for surveillance?', neoadjuvant treatment plus irradiation, neoadjuvant treatment plus radical prostatectomy, perineal radical prostatectomy, because of a low probability of extracapsular extension or positive lymph nodes, adjuvant therapy after local treatment with curative intent as opposed to progression-based treatment or immediate systemic treatment, let alone intermittent endocrine manipulation, are not reliably possible. The outcomes of the few available studies based on prognostic factors should be studied carefully. If considered, a valuable new way of estimating artificial neural networks is a possibility to come to practical terms.
Rigid Macroporous Polymer Monoliths (1999)

In the area of crosslinked chemical supports, continuous media such as rigid macroporous polymer monoliths have certain advantages. Following an introduction to monolithic porous polymer materials, the various applications of macroporous polymer monoliths are reviewed. The Figure shows an SEM image of a monolith prepared within the confines of a polyimide-coated fused silica capillary.
Earthquake signal processing and logging with a battery-powered microcomputer (1980)

abstract A low power microprocessor controlled event-triggered seismic data logging system has been designed and implemented in the ocean bottom seismic capsule. Three channels of seismic data are digitized, formated, and stored under control of an Intersil IM6100 microprocessor chip. The processor also controls event triggering, acoustic diagnostics, battery voltage monitoring, and self-diagnostic functions. A watchdog system restarts it in the rare case of a failure of proper program sequencing. The entire system consumes less than 0.15 watts in the idle mode. The event triggering algorithm consists of first measuring the ratio of the short-term signal average to the long-term signal average, with amplifier offset removed (STA/LTA ratio). When an STA/LTA trigger occurs, the number of slope reversals in the signal begin to be counted. After a preset time following the first STA/LTA trigger, if the number of subsequent STA/LTA triggers meet preset criteria, a system trigger is declared and data is stored on a 4-track Braemar cassette tape deck with 15-M-bit capacity. Various system diagnostics, unit and experiment identification, and battery voltages are recorded at the beginning of each new event record. Digital filters for the long- and short-term averages, and antialiasing have been efficiently implemented by dividing or multiplying by factors of 2, exclusively. This amounts to a shift right or left of a binary number. The recording system has been tested in numerous field experiments. Circuit cards from the ocean bottom capsule implementation are being assembled and used for land stations and could be applied to a wide variety of data acquisition tasks.
HnRNP L binds a cis-acting RNA sequence element that enables intron-dependent gene expression. (1995)

Most pre-mRNAs require an intron for efficient processing in higher eukaryotes. To test the hypothesis that intron-independent gene expression involves positive, cis-acting RNA sequence elements, we constructed chimeric genes in which various regions of the naturally intronless HSV-TK gene were inserted into an intronless variant of the highly intron-dependent human beta-globin gene. Using a transient transfection assay, we identified a 119-nucleotide sequence element contained within the transcribed region of the HSV-TK gene that enables efficient cytoplasmic accumulation of globin RNA in the absence of splicing. RNA UV-cross-linking assays indicated that a 68-kD protein present in nuclear extracts of HeLa and COS cells specifically binds to this HSV-TK sequence element. This 68-kD protein was found to cross-react with an antiserum specific to hnRNP L. Recombinant hnRNP L was shown to bind with high sequence specificity to this RNA sequence element. Analysis of substitution mutants in this element indicated that binding of hnRNP L correlates with accumulation of the RNA in the cytoplasm. Thus, we conclude that (1) hnRNP L binds in a sequence-specific manner to this RNA sequence element that enables intron-independent gene expression, and (2) intron-independent pre-mRNA processing and transport involves sequence-specific RNA-protein interactions between cis-acting RNA sequence elements and proteins such as hnRNP L. This sequence element may be of general use for the efficient expression of cDNA versions of intron-dependent genes.
Role of Leukotrienes on Coronary Vasoconstriction in Isolated Hearts of Arthritic Rats: Effect of in vivo Treatment with CI-986, a Dual Inhibitor of Cyclooxygenase and Lipoxygenase (2000)

In this study, coronary perfusion pressure and force of contraction were investigated in isolated hearts removed from arthritic rats by using the Langendorff method. A strong coronary vasoconstriction was determined in arthritic hearts which was associated with elevated levels of arachidonate 5-lipoxygenase (5-LOX) products, leukotriene B(4) (LTB(4)) and LTC(4) in coronary effluents. In vivo treatment with the dual inhibitor of cyclooxygenase (COX) and LOX, CI-986 (2 and 10 mg/kg/day) on days 14- 26 following adjuvant injection, prevented the coronary vasoconstriction and the increased production of LTB(4) and LTC(4). These results suggest that the coronary vasoconstriction in the isolated arthritic hearts is associated with an increased activity of the LOX system and CI-986 could have a preventive effect on constriction of coronary arteries.
Ganglioside GM3 Participates in the Pathological Conditions of Insulin Resistance (2002)

Gangliosides are known as modulators of transmembrane signaling by regulating various receptor functions. We have found that insulin resistance induced by tumor necrosis factor-alpha (TNF-alpha) in 3T3-L1 adipocytes was accompanied by increased GM3 ganglioside expression caused by elevating GM3 synthase activity and its mRNA. We also demonstrated that TNF-alpha simultaneously produced insulin resistance by uncoupling insulin receptor activity toward insulin receptor substrate-1 (IRS-1) and suppressing insulin-sensitive glucose transport. Pharmacological depletion of GM3 in adipocytes by an inhibitor of glucosylceramide synthase prevented the TNF-alpha-induced defect in insulin-dependent tyrosine phosphorylation of IRS-1 and also counteracted the TNF-alpha-induced serine phosphorylation of IRS-1. Moreover, when the adipocytes were incubated with exogenous GM3, suppression of tyrosine phosphorylation of insulin receptor and IRS-1 and glucose uptake in response to insulin stimulation was observed, demonstrating that GM3 itself is able to mimic the effects of TNF on insulin signaling. We used the obese Zucker fa/fa rat and ob/ob mouse, which are known to overproduce TNF-alpha mRNA in adipose tissues, as typical models of insulin resistance. We found that the levels of GM3 synthase mRNA in adipose tissues of these animals were significantly higher than in their lean counterparts. Taken together, the increased synthesis of cellular GM3 by TNF may participate in the pathological conditions of insulin resistance in type 2 diabetes.
A Finite-State Approach to Phrase-Based Statistical Machine Translation (2012)

This paper presents a finite-state approach to phrase-based statistical machine translation where a log-linear modelling framework is implemented by means of an on-the-fly composition of weighted finite-state transducers. Moses, a well-known state-of-the-art system, is used as a machine translation reference in order to validate our results by comparison. Experiments on the TED corpus achieve a similar performance to that yielded by Moses. 1
Overexpression of mouse D-type cyclins accelerates G1 phase in rodent fibroblasts. (1993)

Mammalian D-type cyclins are growth factor-regulated, delayed early response genes that are presumed to control progression through the G1 phase of the cell cycle by governing the activity of cyclin-dependent kinases (cdks). Overexpression of mouse cyclin D1 in serum-stimulated mouse NIH-3T3 and rat-2 fibroblasts increased their rates of G0 to S- and G1- to S-phase transit by several hours, leading to an equivalent contraction of their mean cell generation times. Although such cells remained contact inhibited and anchorage dependent, they manifested a reduced serum requirement for growth and were smaller in size than their normal counterparts. Ectopic expression of cyclin D2 in rodent fibroblasts, either alone or together with exogenous cdk4, shortened their G0- to S-phase interval and reduced their serum dependency, but cyclin D2 alone did not alter cell size significantly. When cells were microinjected during the G1 interval with a monoclonal antibody specifically reactive to cyclin D1, parental rodent fibroblasts and derivatives overexpressing this cyclin were inhibited from entering S phase, but cells injected near the G1/S phase transition were refractory to antibody-induced growth suppression. Thus, cyclin D1, and most likely D2, are rate limiting for G1 progression.
Development of PD-1/PD-L1 Pathway in Tumor Immune Microenvironment and Treatment for Non-Small Cell Lung Cancer (2015)

Lung cancer is currently the leading cause of cancer-related death in worldwide, non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers. Surgery, platinum-based chemotherapy, molecular targeted agents and radiotherapy are the main treatment of NSCLC. With the strategies of treatment constantly improving, the prognosis of NSCLC patients is not as good as before, new sort of treatments are needed to be exploited. Programmed death 1 (PD-1) and its ligand PD-L1 play a key role in tumor immune escape and the formation of tumor microenvironment, closely related with tumor generation and development. Blockading the PD-1/PD-L1 pathway could reverse the tumor microenvironment and enhance the endogenous antitumor immune responses. Utilizing the PD-1 and/or PD-L1 inhibitors has shown benefits in clinical trials of NSCLC. In this review, we discuss the basic principle of PD-1/PD-L1 pathway and its role in the tumorigenesis and development of NSCLC. The clinical development of PD-1/PD-L1 pathway inhibitors and the main problems in the present studies and the research direction in the future will also be discussed.
Leukoregulin, a T cell-derived cytokine, induces IL-8 gene expression and secretion in human skin fibroblasts. Demonstration and secretion in human skin fibroblasts. Demonstration of enhanced NF-kappa B binding and NF-kappa B-driven promoter activity (1992)

It was shown previously that leukoregulin (LR), a T cell-derived cytokine with unique antitumor properties, modulates fibroblast functions in vitro, including prostaglandin production, matrix synthesis, and protease gene expression. Here, we have focused on the ability of LR to modulate IL-8 gene expression in human dermal fibroblasts. Using a specific ELISA, we demonstrated a dose-dependent enhancement of IL-8 production by LR, accompanied by a parallel elevation of the corresponding mRNA levels, as measured by Northern hybridizations. Maximum accumulation of IL-8 mRNA was observed after 6 h of incubation with LR, and the elevation persisted over 24 h. Inhibition of protein synthesis by cycloheximide resulted in superinduction of IL-8 mRNAs by LR. Dexamethasone, all-trans-retinoic acid, and TGF-beta 1 failed to counteract the effect of LR on IL-8 gene expression. Transient cell transfections with an IL-8 promoter/CAT reporter gene construct showed a dose-dependent enhancement of the promoter activity by LR, suggesting transcriptional regulation. Gel shift assays with oligonucleotides containing the consensus NF-kappa B binding sequences of the IL-8 and Ig kappa light chain genes showed enhanced binding activity in nuclear extracts from cells incubated with LR. Transient transfection experiments using a NF-kappa B/SV2 promoter-CAT reporter gene construct showed enhanced CAT activity by LR. Taken together, these data suggest that LR may up-regulate IL-8 gene expression by activation of the binding of NF-kappa B to the corresponding cis-acting element in the IL-8 promoter. Our results demonstrate that LR, together with IL-1 and TNF-alpha, could participate in the recruitment of neutrophils to the sites of inflammation by induction of IL-8 production in fibroblasts.
Tissue Biomarkers for Prognosis in Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-analysis (2011)

We noted that that there was incomplete adherence to the REMARK guidelines with inadequate methodology reporting as well as failure to perform multivariate analysis. Addressing the persistent incomplete adoption of these criteria may eventually result in the incorporation of molecular marker assessment within PDAC management algorithms.
Antibody targeting intracellular oncogenic Ras mutants exerts anti-tumour effects after systemic administration (2017)

Oncogenic Ras mutants, frequently detected in human cancers, are high-priority anticancer drug targets. However, direct inhibition of oncogenic Ras mutants with small molecules has been extremely challenging. Here we report the development of a human IgG1 format antibody, RT11, which internalizes into the cytosol of living cells and selectively binds to the activated GTP-bound form of various oncogenic Ras mutants to block the interactions with effector proteins, thereby suppressing downstream signalling and exerting anti-proliferative effects in a variety of tumour cells harbouring oncogenic Ras mutants. When systemically administered, an RT11 variant with an additional tumour-associated integrin binding moiety for tumour tissue targeting significantly inhibits the in vivo growth of oncogenic Ras-mutated tumour xenografts in mice, but not wild-type Ras-harbouring tumours. Our results demonstrate the feasibility of developing therapeutic antibodies for direct targeting of cytosolic proteins that are inaccessible using current antibody technology.
Follow‐up of circulatory changes secondary to deep venous thrombosis with special regards to radionuclide tests (1986)

The influence of circulatory changes, which are secondary to deep venous thrombosis (DVT) in the leg, on result of radionuclide tests was studied in eight patients. Strain gauge plethysmography, a radionuclide blood-pool test and phlebography were performed both in the acute phase and during recovery up to 6 months after the initial admission. Morphological and functional changes were correlated with results from repeatedly performed 99Tcm-plasmin tests, a test currently used for diagnosis of DVT. In the acute phase, the thrombotic leg showed an increase in pooled blood and, in the case of proximal thrombosis, also impaired venous outflow. During the 6-month follow-up complete recanalization was observed in three patients and partial recanalization in five. The circulatory changes were found to recover progressively and earlier than the morphological changes. The 99Tcm-plasmin test was pathological at admission in all patients. It was normalized in parallel with plethysmography and blood-pool test results, at a time when morphological recovery was still incomplete. These findings confirm that a positive 99Tcm-plasmin test reflects haemodynamic changes which are secondary to the DVT rather than a specific binding of the radiopharmaceutical to the thrombus. The 99Tcm-plasmin test was normalized from 1 to more than 26 weeks after an acute DVT. This finding is of practical importance when using radionuclide tests for evaluation of acute recurrent DVT.
New Uses for the Burgess Reagent in Chemical Synthesis: Methods for the Facile and Stereoselective Formation of Sulfamidates, Glycosylamines, and Sulfamides (2004)

Although the Burgess reagent (methoxycarbonylsulfamoyltriethylammonium hydroxide, inner salt) has found significant use in chemical synthesis as a dehydrating agent, almost no work has been directed towards its potential in other synthetic applications. As this article will detail, we have found that the Burgess reagent is remarkably effective at accomplishing a number of non-dehydrative synthetic tasks when applied to appropriate substrates, such as the formation of sulfamidates from 1,2-diols or epoxyalcohols, alpha- and beta-glycosylamines from carbohydrates, and cyclic sulfamides from 1,2-aminoalcohols. Beyond delineating the power of these new reaction manifolds, we also describe the construction of a group of alternative Burgess-type reagents that extends the scope of these new reactions even further.
Sympathetic neural mechanisms in obstructive sleep apnea. (1995)

Blood pressure, heart rate, sympathetic nerve activity, and polysomnography were recorded during wakefulness and sleep in 10 patients with obstructive sleep apnea. Measurements were also obtained after treatment with continuous positive airway pressure (CPAP) in four patients. Awake sympathetic activity was also measured in 10 age- and sex-matched control subjects and in 5 obese subjects without a history of sleep apnea. Patients with sleep apnea had high levels of nerve activity even when awake (P < 0.001). Blood pressure and sympathetic nerve activity did not fall during any stage of sleep. Mean blood pressure was 92 +/- 4.5 mmHg when awake and reached peak levels of 116 +/- 5 and 127 +/- 7 mmHg during stage II sleep (n = 10) and rapid eye movement (REM) sleep (n = 5), respectively (P < 0.001). Sympathetic activity increased during sleep (P = 0.01) especially during stage II (133 +/- 9% above wakefulness; P = 0.006) and REM (141 +/- 13%; P = 0.007). Peak sympathetic activity (measured over the last 10 s of each apneic event) increased to 299 +/- 96% during stage II sleep and to 246 +/- 36% during REM sleep (both P < 0.001). CPAP decreased sympathetic activity and blood pressure during sleep (P < 0.03). We conclude that patients with obstructive sleep apnea have high sympathetic activity when awake, with further increases in blood pressure and sympathetic activity during sleep. These increases are attenuated by treatment with CPAP.
Inhibition of the development of suppressor cells in culture by 4-hydroperoxycyclophosphamide (1984)

Abstract The effect of 4-hydroperoxycyclophosphamide (4-OOH-CYP), an in vitro active form of cyclophosphamide, on the development of the suppressor cells that modulate the cytotoxic T cell response to alloantigens was investigated. Treatment of spleen cells with 4-OOH-CYP inhibited the development of suppression in culture but did not prevent the development of cytotoxicity to alloantigens. The effects of 4-OOH-CYP pretreatment at a concentration of 15 microM were found to be specific for Thy-1.2+ suppressor cells and inhibited suppressor function in a dose-dependent fashion (ED50 = 7.86 ± 0.29 microM). The 4-OOH-CYP-sensitive suppressor precursor population is most likely Lyt-1+2+ whereas differentiated suppressor cells are of the Lyt-1-2+ phenotype. These results demonstrate that 4-OOH-CYP can be utilized in vitro to separate functionally distinct immunoregulatory T cell subsets.
An Infrared νNH Scale for Weakly Basic Anions. Implications for Single-Molecule Acidity and Superacidity (2006)

The N-H stretching frequencies of tri-n-octylammonium salts are reported for a series of weakly basic anions (A(-)), many of which are the conjugate bases of known strong acids and superacids. Data have been collected primarily in carbon tetrachloride, where Oct(3)N(+)-H...A(-) contact ion pairs are formed. In the more polar solvent 1,2-dichloroethane, some salts form both contact and solvent-separated ion pairs. Salts have also been studied in crystalline form or as oils. In general, the nuNH frequencies decrease in the order fluoroanions > carboranes > oxyanions, reflecting the relative basicities of the anions. By inference, the data reflect differences in the acidity of the corresponding conjugate acids (HA). This qualitative indicator of acid strength is useful because it reflects acidity on an individual molecule basis rather than in bulk. In this respect, it provides a condensed-phase analogy to gas-phase ("intrinsic") acidity and gives insight into the aggregation phenomena that determine bulk acidity. The data also reveal the importance of the chemical stability of conjugate base anions in attaining high acidity and suggest where acids stronger than those presently known may be discovered.
Formation of Aryl−Nitrogen, Aryl−Oxygen, and Aryl−Carbon Bonds Using Well-Defined Copper(I)-Based Catalysts (2001)

We report mild synthetic protocols for the formation of aryl-carbon, aryl-nitrogen, and aryl-oxygen bonds based on soluble, well-defined copper(I) catalysts. These protocols do not require the use of palladium and/or expensive ligands. [structure: see text]
Nuclear Export of MicroRNA Precursors (2003)

MicroRNAs (miRNAs), which function as regulators of gene expression in eukaryotes, are processed from larger transcripts by sequential action of nuclear and cytoplasmic ribonuclease III-like endonucleases. We show that Exportin-5 (Exp5) mediates efficient nuclear export of short miRNA precursors (pre-miRNAs) and that its depletion by RNA interference results in reduced miRNA levels. Exp5 binds correctly processed pre-miRNAs directly and specifically, in a Ran guanosine triphosphate-dependent manner, but interacts only weakly with extended pre-miRNAs that yield incorrect miRNAs when processed by Dicer in vitro. Thus, Exp5 is key to miRNA biogenesis and may help coordinate nuclear and cytoplasmic processing steps.