Natural extension of choice functions

International Conference on Information Processing and Management of Uncertainty in Knowledge-Based Systems, IPMU (17 th, 2018, Cádiz, Spain

Testing the noble gas paleothermometer with a yearlong study of groundwater noble gases in an instrumented monitoring well

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94795/1/wrcr13235.pd

Pharmacological levels of withaferin A (Withania somnifera) trigger clinically relevant anticancer effects specific to triple negative breast cancer cells

Withaferin A (WA) isolated from Withania somnifera (Ashwagandha) has recently become an attractive phytochemical under investigation in various preclinical studies for treatment of different cancer types. In the present study, a comparative pathway-based transcriptome analysis was applied in epithelial-like MCF-7 and triple negative mesenchymal MDA-MB-231 breast cancer cells exposed to different concentrations of WA which can be detected systemically in in vivo experiments. Whereas WA treatment demonstrated attenuation of multiple cancer hallmarks, the withanolide analogue Withanone (WN) did not exert any of the described effects at comparable concentrations. Pathway enrichment analysis revealed that WA targets specific cancer processes related to cell death, cell cycle and proliferation, which could be functionally validated by flow cytometry and real-time cell proliferation assays. WA also strongly decreased MDA-MB-231 invasion as determined by single-cell collagen invasion assay. This was further supported by decreased gene expression of extracellular matrix-degrading proteases (uPA, PLAT, ADAM8), cell adhesion molecules (integrins, laminins), pro-inflammatory mediators of the metastasis-promoting tumor microenvironment (TNFSF12, IL6, ANGPTL2, CSF1R) and concomitant increased expression of the validated breast cancer metastasis suppressor gene (BRMS1). In line with the transcriptional changes, nanomolar concentrations of WA significantly decreased protein levels and corresponding activity of uPA in MDA-MB-231 cell supernatant, further supporting its anti-metastatic properties. Finally, hierarchical clustering analysis of 84 chromatin writer-reader-eraser enzymes revealed that WA treatment of invasive mesenchymal MDA-MB-231 cells reprogrammed their transcription levels more similarly towards the pattern observed in non-invasive MCF-7 cells. In conclusion, taking into account that sub-cytotoxic concentrations of WA target multiple metastatic effectors in therapy-resistant triple negative breast cancer, WA-based therapeutic strategies targeting the uPA pathway hold promise for further (pre)clinical development to defeat aggressive metastatic breast cancer

Resolving the genetic heterogeneity of prelingual hearing loss within one family: Performance comparison and application of two targeted next generation sequencing approaches.

published_or_final_versio

Longitudinal proxy measurements in multiple sclerosis: patient-proxy agreement on the impact of MS on daily life over a period of two years

Background: The use of self- report measurements in clinical settings is increasing. However, in patients with limitations that interfere with reliable self- assessment such as cognitive impairment or mood disturbances, as may be the case in multiple sclerosis ( MS), data collection might be problematic. In these situations, information obtained from proxy respondents ( e. g. partners) may replace self- ratings. The aim of this study was to examine the value of proxy ratings at separate points in time and to assess patient- proxy agreement on possible changes in disease impact of MS. Methods: Fifty- six MS patients and their partners completed the Multiple Sclerosis Impact Scale ( MSIS- 29) at baseline and follow- up, two years later. Patient- proxy agreement was assessed at both time points by calculating intraclass correlation coefficients ( ICCs), exact and global agreement and the mean directional differences between groups. Agreement of change over time was assessed by calculating ICCs between change scores. In parallel, global ratings of both patients and proxy respondents of the extent to which the patient had improved or deteriorated over the past two years were collected to validate possible changes on the MSIS- 29. Results: At both time points, agreement on the physical scale was higher than agreement on the psychological scale ( ICCs at baseline were 0.81 for the physical scale and 0.72 for the psychological scale; at follow- up, the ICC values were 0.86 and 0.65 respectively). At follow- up, statistically significant mean differences between patients and proxies were noted for the physical scale (- 4.8 +/- 12.7, p = 0.006) and the psychological scale (- 8.9 +/- 18.8, p = 0.001). Agreement between change scores on the MSIS- 29 was fair ( ICC < 0.60). Our analyses suggest that the validity of measuring changes over time might be better for proxy respondents compared to patients. Conclusion: Proxy respondents could act as a reliable source of information in cross- sectional studies. Moreover, results suggested that agreement on change over time might be better for proxy respondents compared to patients. Although this remarkable finding should be interpreted cautiously because of several limitations of the study, it does plead for further investigation of this important topic

Validation of tissue microarray technology in squamous cell carcinoma of the esophagus

Tissue microarray (TMA) technology has been developed to facilitate high-throughput immunohistochemical and in situ hybridization analysis of tissues by inserting small tissue biopsy cores into a single paraffin block. Several studies have revealed novel prognostic biomarkers in esophageal squamous cell carcinoma (ESCC) by means of TMA technology, although this technique has not yet been validated for these tumors. Because representativeness of the donor tissue cores may be a disadvantage compared to full sections, the aim of this study was to assess if TMA technology provides representative immunohistochemical results in ESCC. A TMA was constructed containing triplicate cores of 108 formalin-fixed, paraffin-embedded squamous cell carcinomas of the esophagus. The agreement in the differentiation grade and immunohistochemical staining scores of CK5/6, CK14, E-cadherin, Ki-67, and p53 between TMA cores and a subset of 64 randomly selected donor paraffin blocks was determined using kappa statistics. The concurrence between TMA cores and donor blocks was moderate for Ki-67 (κ = 0.42) and E-cadherin (κ = 0.47), substantial for differentiation grade (κ = 0.65) and CK14 (κ = 0.71), and almost perfect for p53 (κ = 0.86) and CK5/6 (κ = 0.93). TMA technology appears to be a valid method for immunohistochemical analysis of molecular markers in ESCC provided that the staining pattern in the tumor is homogeneous

Tongue lesions in psoriasis: a controlled study

BACKGROUND: Our objective was to study tongue lesions and their significance in psoriatic patients. METHODS: The oral mucosa was examined in 200 psoriatic patients presenting to Razi Hospital in Tehran, Iran, and 200 matched controls. RESULTS: Fissured tongue (FT) and benign migratory glossitis (BMG) were the two most frequent findings. FT was seen more frequently in psoriatic patients (n = 66, 33%) than the control group (n = 19, 9.5%) [odds ratio (OR): 4.69; 95% confidence interval (CI): 2.61–8.52] (p-value < 0.0001). BMG, too, was significantly more frequent in psoriatic patients (28 cases, 14%) than the control group (12 cases, 6%) (OR: 2.55; 95% CI: 1.20–5.50) (p-value < 0.012). In 11 patients (5.5%), FT and BMG coexisted. FT was more frequent in pustular psoriasis (7 cases, 53.8%) than erythemato-squamous types (56 cases, 30.4%). On the other hand, the frequency of BMG increased with the severity of psoriasis in plaque-type psoriasis assessed by psoriasis area and severity index (PASI) score. CONCLUSIONS: Nonspecific tongue lesions are frequently observed in psoriasis. Further studies are recommended to substantiate the clinical significance of these seemingly nonspecific findings in suspected psoriatic cases

Critical Exponents, Hyperscaling and Universal Amplitude Ratios for Two- and Three-Dimensional Self-Avoiding Walks

We make a high-precision Monte Carlo study of two- and three-dimensional self-avoiding walks (SAWs) of length up to 80000 steps, using the pivot algorithm and the Karp-Luby algorithm. We study the critical exponents $\nu$ and $2\Delta_4 -\gamma$ as well as several universal amplitude ratios; in particular, we make an extremely sensitive test of the hyperscaling relation $d\nu = 2\Delta_4 -\gamma$. In two dimensions, we confirm the predicted exponent $\nu = 3/4$ and the hyperscaling relation; we estimate the universal ratios $\ / \ = 0.14026 \pm 0.00007$, $\ / \ = 0.43961 \pm 0.00034$ and $\Psi^* = 0.66296 \pm 0.00043$ (68\% confidence limits). In three dimensions, we estimate $\nu = 0.5877 \pm 0.0006$ with a correction-to-scaling exponent $\Delta_1 = 0.56 \pm 0.03$ (subjective 68\% confidence limits). This value for $\nu$ agrees excellently with the field-theoretic renormalization-group prediction, but there is some discrepancy for $\Delta_1$. Earlier Monte Carlo estimates of $\nu$, which were $\approx\! 0.592$, are now seen to be biased by corrections to scaling. We estimate the universal ratios $\ / \ = 0.1599 \pm 0.0002$ and $\Psi^* = 0.2471 \pm 0.0003$; since $\Psi^* > 0$, hyperscaling holds. The approach to $\Psi^*$ is from above, contrary to the prediction of the two-parameter renormalization-group theory. We critically reexamine this theory, and explain where the error lies.Comment: 87 pages including 12 figures, 1029558 bytes Postscript (NYU-TH-94/09/01

Search for Gravitational Waves from Primordial Black Hole Binary Coalescences in the Galactic Halo

We use data from the second science run of the LIGO gravitational-wave detectors to search for the gravitational waves from primordial black hole (PBH) binary coalescence with component masses in the range 0.2--$1.0 M_\odot$. The analysis requires a signal to be found in the data from both LIGO observatories, according to a set of coincidence criteria. No inspiral signals were found. Assuming a spherical halo with core radius 5 kpc extending to 50 kpc containing non-spinning black holes with masses in the range 0.2--$1.0 M_\odot$, we place an observational upper limit on the rate of PBH coalescence of 63 per year per Milky Way halo (MWH) with 90% confidence.Comment: 7 pages, 4 figures, to be submitted to Phys. Rev.