Tumour Fas ligand:Fas ratio greater than 1 is an independent marker of relative resistance to tamoxifen therapy in hormone receptor positive breast cancer

BACKGROUND: The objective of the present study was to examine the prognostic and predictive significance of the apoptosis-related marker Fas ligand (FasL):Fas ratio in breast cancer. METHODS: Tumour biopsies from 215 primary invasive breast cancer patients were examined for the expression of FasL and Fas mRNA transcripts by quantitative real-time RT-PCR. Their prognostic and predictive impact on patient survival was determined in univariate and multivariate survival analyses. RESULTS: Using a cutoff value of 1, a FasL:Fas ratio greater than 1 was found to have significant prognostic value for disease-free survival among the total population (median follow up 54 months). It was associated with a significantly decreased disease-free survival (P = 0.022) and with a tendency toward increased mortality (P = 0.14) in univariate analysis. Hormone receptor positive women exclusively treated with tamoxifen (n = 86) and with a FasL:Fas ratio greater than 1 had a significantly decreased disease-free survival (P = 0.008) and overall survival (P = 0.03) in univariate Kaplan–Meier analysis. Furthermore, tumour size and FasL:Fas ratio were of independent predictive significance in the multivariate model for disease-free and overall survival in that subgroup. Among postmenopausal patients (n = 148) both of those factors retained independent prognostic significance in the multivariate model for disease-free survival. In contrast, FasL:Fas ratio had no significant predictive value in patients exclusively treated with chemotherapy. CONCLUSION: The data presented indicate that FasL:Fas ratio may be useful not only as a prognostic factor but also as a predictive factor for projecting response to the antioestrogen tamoxifen. The results strongly support a correlation between FasL:Fas ratio greater than 1 and lack of efficacy of tamoxifen in hormone receptor positive patients

Chemosensory Event-Related Potentials in Response to Nasal Propylene Glycol Stimulation

Propylene glycol, also denoted as 1.2 propanediol (C3H8O2), often serves as a solvent for dilution of olfactory stimuli. It is supposed to serve as a neutral substance and has been used in many behavioral and electrophysiological studies to dilute pure olfactory stimuli. However, the effect of propylene glycol on perception and on neuronal responses has hitherto never been studied. In this study we tested by means of a threshold test, whether a nasal propylene glycol stimulation is recognizable by humans. Participants were able to recognize propylene glycol at a threshold of 42% concentration and reported a slight cooling effect. In addition to the threshold test, we recorded electroencephalography (EEG) during nasal propylene glycol stimulation to study the neuronal processing of the stimulus. We used a flow olfactometer and stimulated 15 volunteers with three different concentrations of propylene glycol (40 trials each) and water as a control condition (40 trials). To evaluate the neuronal response, we analyzed the event-related potentials (ERPs) and power modulations. The task of the volunteers was to identify a change (olfactory, thermal, or tactile) in the continuous air flow generated by the flow olfactometer. The analysis of the ERPs showed that propylene glycol generates a clear P2 component, which was also visible in the frequency domain as an evoked power response in the theta-band. The source analysis of the P2 revealed a widespread involvement of brain regions, including the postcentral gyrus, the insula and adjacent operculum, the thalamus, and the cerebellum. Thus, it is possible that trigeminal stimulation can at least partly account for sensations and brain responses elicited by propylene glycol. Based on these results, we conclude that the use of high propylene glycol concentrations to dilute fragrances complicates the interpretation of presumed purely olfactory effects

The high-rate data challenge: computing for the CBM experiment

The Compressed Baryonic Matter experiment (CBM) is a next-generation heavy-ion experiment to be operated at the FAIR facility, currently under construction in Darmstadt, Germany. A key feature of CBM is very high interaction rate, exceeding those of contemporary nuclear collision experiments by several orders of magnitude. Such interaction rates forbid a conventional, hardware-triggered readout; instead, experiment data will be freely streaming from self-triggered front-end electronics. In order to reduce the huge raw data volume to a recordable rate, data will be selected exclusively on CPU, which necessitates partial event reconstruction in real-time. Consequently, the traditional segregation of online and offline software vanishes; an integrated on- and offline data processing concept is called for. In this paper, we will report on concepts and developments for computing for CBM as well as on the status of preparations for its first physics run

A precision device needs precise simulation: Software description of the CBM Silicon Tracking System

Precise modelling of detectors in simulations is the key to the understanding of their performance, which, in turn, is a prerequisite for the proper design choice and, later, for the achievement of valid physics results. In this report, we describe the implementation of the Silicon Tracking System (STS), the main tracking device of the CBM experiment, in the CBM software environment. The STS makes uses of double-sided silicon micro-strip sensors with double metal layers. We present a description of transport and detector response simulation, including all relevant physical effects like charge creation and drift, charge collection, cross-talk and digitization. Of particular importance and novelty is the description of the time behavior of the detector, since its readout will not be externally triggered but continuous. We also cover some aspects of local reconstruction, which in the CBM case has to be performed in real-time and thus requires high-speed algorithms

Study of exclusive one-pion and one-eta production using hadron and dielectron channels in pp reactions at kinetic beam energies of 1.25 GeV and 2.2 GeV with HADES

We present measurements of exclusive ensuremathπ+,0 and η production in pp reactions at 1.25GeV and 2.2GeV beam kinetic energy in hadron and dielectron channels. In the case of π+ and π0 , high-statistics invariant-mass and angular distributions are obtained within the HADES acceptance as well as acceptance-corrected distributions, which are compared to a resonance model. The sensitivity of the data to the yield and production angular distribution of Δ (1232) and higher-lying baryon resonances is shown, and an improved parameterization is proposed. The extracted cross-sections are of special interest in the case of pp → pp η , since controversial data exist at 2.0GeV; we find \ensuremathσ=0.142±0.022 mb. Using the dielectron channels, the π0 and η Dalitz decay signals are reconstructed with yields fully consistent with the hadronic channels. The electron invariant masses and acceptance-corrected helicity angle distributions are found in good agreement with model predictions

Identification of Y-Box Binding Protein 1 As a Core Regulator of MEK/ERK Pathway-Dependent Gene Signatures in Colorectal Cancer Cells

Transcriptional signatures are an indispensible source of correlative information on disease-related molecular alterations on a genome-wide level. Numerous candidate genes involved in disease and in factors of predictive, as well as of prognostic, value have been deduced from such molecular portraits, e.g. in cancer. However, mechanistic insights into the regulatory principles governing global transcriptional changes are lagging behind extensive compilations of deregulated genes. To identify regulators of transcriptome alterations, we used an integrated approach combining transcriptional profiling of colorectal cancer cell lines treated with inhibitors targeting the receptor tyrosine kinase (RTK)/RAS/mitogen-activated protein kinase pathway, computational prediction of regulatory elements in promoters of co-regulated genes, chromatin-based and functional cellular assays. We identified commonly co-regulated, proliferation-associated target genes that respond to the MAPK pathway. We recognized E2F and NFY transcription factor binding sites as prevalent motifs in those pathway-responsive genes and confirmed the predicted regulatory role of Y-box binding protein 1 (YBX1) by reporter gene, gel shift, and chromatin immunoprecipitation assays. We also validated the MAPK-dependent gene signature in colorectal cancers and provided evidence for the association of YBX1 with poor prognosis in colorectal cancer patients. This suggests that MEK/ERK-dependent, YBX1-regulated target genes are involved in executing malignant properties

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Search for heavy resonances decaying to two Higgs bosons in final states containing four b quarks

A search is presented for narrow heavy resonances X decaying into pairs of Higgs bosons (H) in proton-proton collisions collected by the CMS experiment at the LHC at root s = 8 TeV. The data correspond to an integrated luminosity of 19.7 fb(-1). The search considers HH resonances with masses between 1 and 3 TeV, having final states of two b quark pairs. Each Higgs boson is produced with large momentum, and the hadronization products of the pair of b quarks can usually be reconstructed as single large jets. The background from multijet and t (t) over bar events is significantly reduced by applying requirements related to the flavor of the jet, its mass, and its substructure. The signal would be identified as a peak on top of the dijet invariant mass spectrum of the remaining background events. No evidence is observed for such a signal. Upper limits obtained at 95 confidence level for the product of the production cross section and branching fraction sigma(gg -> X) B(X -> HH -> b (b) over barb (b) over bar) range from 10 to 1.5 fb for the mass of X from 1.15 to 2.0 TeV, significantly extending previous searches. For a warped extra dimension theory with amass scale Lambda(R) = 1 TeV, the data exclude radion scalar masses between 1.15 and 1.55 TeV

Search for supersymmetry in events with one lepton and multiple jets in proton-proton collisions at root s=13 TeV

Peer reviewe

Measurement of the top quark mass using charged particles in pp collisions at root s=8 TeV

Peer reviewe