RUNX3 attenuates beta-catenin/T cell factors in intestinal tumorigenesis

In intestinal epithelial cells, inactivation of APC, a key regulator of the Wnt pathway, activates beta-catenin to initiate tumorigenesis. However, other alterations may be involved in intestinal tumorigenesis. Here we found that RUNX3, a gastric tumor suppressor, forms a ternary complex with beta-catenin/7CF4 and attenuates Wnt signaling activity. A significant fraction of human sporadic colorectal adenomas and Runx3(+/-) mouse intestinal adenomas showed inactivation of RUNX3 without apparent beta-catenin accumulation, indicating that RUNX3 inactivation independently induces intestinal adenomas. In human colon cancers, RUNX3 is frequently inactivated with concomitant beta-catenin accumulation, suggesting that adenomas induced by inactivation of RUNX3 may progress to malignancy. Taken together, these data demonstrate that RUNX3 functions as a tumor suppressor by attenuating Wnt signaling.

A 7000 yr perspective on volcanic ash clouds affecting northern Europe

The ash cloud resulting from the 2010 eruption of Eyjafjöll caused severe disruption to air travel across Europe but as a geological event, it is not unprecedented. Analysis of peat and lake sediments from northern Europe has revealed the presence of microscopic layers of Icelandic volcanic ash (tephra). These sedimentary records, together with historical records of Holocene ash falls, demonstrate that Icelandic volcanoes have generated substantial ash clouds that reached northern Europe many times. Here we present the first comprehensive compilation of sedimentary and historical records of ash-fall events in northern Europe, spanning the last 7000 years. Within this period ten tephra layers have been identified in the Faroe Islands, 14 in Great Britain, 11 in Germany, 38 in Scandinavia and 33 in Ireland. Seven ash fall events have been historically documented prior to the Eyjafjöll 2010 event. Ash fall events appear to be more frequent in the last 1500 years, but it is unclear whether this reflects a true increase in eruption frequency or dispersal, or is an artefact of the records themselves or the way they have been generated. In the last 1,000 years, volcanic ash clouds reached Northern Europe with a mean return interval of 53 ± 8 years (the range of return intervals is between 6 and 112 years). Modelling using the ash records for the last millennium indicates that for any 10 year period there is a 17% probability of tephra fallout event in Northern Europe. These values must be considered as conservative estimates due to the nature of tephra capture and preservation in the sedimentary record.

On the Performance of Eigenvalue-Based Cooperative Spectrum Sensing for Cognitive Radio

In this paper, the distribution of the ratio of extreme eigenvalues of a complex Wishart matrix is studied in order to calculate the exact decision threshold as a function of the desired probability of false alarm for the maximum-minimum eigenvalue (MME) detector. In contrast to the asymptotic analysis reported in the literature, we consider a finite number of cooperative receivers and a finite number of samples and derive the exact decision threshold for the probability of false alarm. The proposed exact formulation is further reduced to the case of two receiver-based cooperative spectrum sensing. In addition, an approximate closed-form formula of the exact threshold is derived in terms of a desired probability of false alarm for a special case having equal number of receive antennas and signal samples. Finally, the derived analytical exact decision thresholds are verified with Monte-Carlo simulations. We show that the probability of detection performance using the proposed exact decision thresholds achieves significant performance gains compared to the performance of the asymptotic decision threshold.

Effect of composition, solvent exchange liquid and drying method on the porous structure of phenol-formaldehyde gels

Organic gels have been synthesized by sol–gel polycondensation of phenol (P) and formaldehyde (F) catalyzed by sodium carbonate (C). The effect of synthesis parameters such as phenol/catalyst ratio (P/C), solvent exchange liquid and drying method, on the porous structure of the gels have been investigated. The total and mesopore volumes of the PF gels increased with increasing P/C ratio in the range of P/C B 8, after this both properties started to decrease with P/C ratio for P/C[8 and the gel with P/C = 8 showed the highest total and mesopore volumes of 1.281 and 1.279 cm3 g-1 respectively. The gels prepared by freeze drying possessed significantly higher porosities than the vacuum dried gels. The pore volume and average pore diameter of the freeze dried gels were significantly higher than those of the vacuum dried gels. T-butanol emerged as the preferred solvent for the removal of water from the PF hydrogel prior to drying, as significantly higher pore volumes and specific surface areas were obtained in the corresponding dried gels. The results showed that freeze drying with t-butanol and lower P/C ratios were favourable conditions for the synthesis of highly mesoporous phenol–formaldehyde gels.

TIME-RESOLVED RESONANCE RAMAN-SPECTROSCOPY OF TRIPLET-STATE METALATED AND FREE-BASE TETRAARYLPORPHYRINS

Resonance Raman spectra of the T-1 excited states of Zn and free-base tetra-4-sulfonatophenylporphyrin (TPPS) have been recorded at room temperature in aqueous solution using two-colour time-resolved methods. The spectra of both sulfonated molecules are very similar to their tetraphenylporphyrin (TPP) analogues, which have been recorded in THF solution using the same pump-probe conditions, but they have higher signal-to-noise ratios because interference from strong solvent bands is reduced. Although two different T-1 spectra of Zn(TPP) have been reported these spectra differ slightly from each other and from the spectrum reported here, which has band positions very close (+/-6 cm(-1)) to those of Zn(TPPS). The high S/N ratios obtainable for the water-soluble porphyrins have allowed reliable polarization data to be recorded for their S-0 and T-1 states. This data set allows a realistic comparison of the changes in bonding associated with excitation of both free-base and Zn tetraarylporphyrins to the T-1 state.

A search for interstellar gas-phase CO2 gas: Solid state abundance ratios

We present searches for gas-phase CO2 features in the ISO-SWS infrared spectra of four deeply embedded massive young stars, which all show strong solid CO2 absorption. The abundance of gas-phase CO2 is at most 2. 10(-7) with respect to H-2, and is less than 5% of that in the solid phase. This is in strong contrast to CO, which is a factor of 10-100 more abundant in the gas than in solid form in these objects. The gas/solid state ratios of CO2, CO and H2O are discussed in terms of the physical and chemical state of the clouds.

The role of the media in a bubble

We examine the role of the news media during the British Railway Mania, arguably one of the largest financial bubbles in history. Our analysis suggests that the press responded to changes in the stock market, and its reporting of recent events may have influenced asset prices. However, we find no evidence that the sentiment of the media, or the attention which it gave to particular stocks, had any influence on exacerbating or ending the Mania. The main contribution of the media was to provide factual information which investors could use to inform their decisions. © 2012 Elsevier Inc.

A helminth cathelicidin-like protein suppresses antigen processing and presentation in macrophages via inhibition of lysosomal vATPase

We previously reported the identification of a novel family of immunomodulatory proteins, termed helminth defense molecules (HDMs), that are secreted by medically important trematode parasites. Since HDMs share biochemical, structural, and functional characteristics with mammalian cathelicidin-like host defense peptides (HDPs), we proposed that HDMs modulate the immune response via molecular mimicry of host molecules. In the present study, we report the mechanism by which HDMs influence the function of macrophages. We show that the HDM secreted by Fasciola hepatica (FhHDM-1) binds to macrophage plasma membrane lipid rafts via selective interaction with phospholipids and/or cholesterol before being internalized by endocytosis. Following internalization, FhHDM-1 is rapidly processed by lysosomal cathepsin L to release a short C-terminal peptide (containing a conserved amphipathic helix that is a key to HDM function), which then prevents the acidification of the endolysosomal compartments by inhibiting vacuolar ATPase activity. The resulting endolysosomal alkalization impedes macrophage antigen processing and prevents the transport of peptides to the cell surface in conjunction with MHC class II for presentation to CD4(+) T cells. Thus, we have elucidated a novel mechanism by which helminth pathogens alter innate immune cell function to assist their survival in the host.-Robinson, M. W., Alvarado, R., To, J., Hutchinson, A. T., Dowdell, S. N., Lund, M., Turnbull, L., Whitchurch, C. B., O'Brien, B. A., Dalton, J. P., Donnelly, S. A helminth cathelicidin-like protein suppresses antigen processing and presentation in macrophages via inhibition of lysosomal vATPase.

Cognitive functioning in subjects with recent-onset psychosis from a low-middle-income environment: Multiple-domain deficits and longitudinal evaluation

Cognitive deficits are a key feature of recent-onset psychosis, but there is no consensus on whether such deficits are generalized or confined to specific domains. Besides, it is unclear whether cognitive deficits: a) are found in psychotic patients in samples from outside high-income countries; and b) whether they progress uniformly over time in schizophrenia and affective psychoses. We applied 12 tests organized into eight cognitive domains, comparing psychosis patients (n = 56, time from initial contact = 677.95+/-183.27 days) versus healthy controls (n = 70) recruited from the same area of Sao Paulo, Brazil. Longitudinal comparisons (digit span and verbal fluency) were conducted between a previous assessment of the subjects carried out at their psychosis onset, and the current follow-up evaluation. Psychosis patients differed significantly from controls on five domains, most prominently on verbal memory. Cognitive deficits remained detectable in separate comparisons of the schizophrenia subgroup and, to a lesser extent, the affective psychosis subjects against controls. Longitudinal comparisons indicated significant improvement in schizophrenia, affective psychoses, and control subjects, with no significant group-by-time interactions. Our results reinforce the view that there are generalized cognitive deficits in association with recent-onset psychoses, particularly of non-affective nature, which persist over time. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

BRCA1 Immunohistochemical Staining as a Prognostic Indicator in Uterine Serous Carcinoma

OBJECTIVES: The objective of this study was to investigate the relationship between BRCA1 protein expression, as determined by immunohistochemistry, and clinical outcome in uterine serous carcinoma (USC). METHODS: A tissue microarray containing duplicate cores of 73 cases of USC was immunohistochemically stained with mouse anti-BRCA1 (Ab-1) mouse monoclonal (MS110) antibody. The cores were scored in a semiquantitative manner evaluating both the distribution and intensity of nuclear staining. BRCA1 protein expression was correlated with progression-free survival. RESULTS: Seventy-two of 73 cases were assessable, and there was a statistically significant decreased progression-free survival for those cases exhibiting tumor cell nuclei staining of 76% or greater (P = 0.0023). CONCLUSIONS: Our study illustrates that a low level of BRCA1 protein expression is a favorable prognostic indicator in USC, similar to what is observed in high-grade serous ovarian carcinoma. Further studies should focus on the BRCA1 status of USCs at a molecular level and also investigate whether BRCA1 protein expression is associated with response to chemotherapy in USC.

Whole wafer magnetostriction metrology for magnetic films and multilayers

The requirements for metrology of magnetostriction in complex multilayers and on whole wafers present challenges. An elegant technique based on radius of curvature deformation of whole wafers in a commercial metrology tool is described. The method is based on the Villari effect through application of strain to a film by introducing a radius of curvature. Strain can be applied tensilely and compressively depending on the material. The design, while implemented on 3'' wafers, is scalable. The approach removes effects arising from any shape anisotropy that occurs with smaller samples, which can lead to a change in magnetic response. From the change in the magnetic anisotropy as a function of the radius, saturation magnetostriction ?s can be determined. Dependence on film composition and film thickness was studied to validate the radius of curvature approach with other techniques. ?s decreases from positive values to negative values through an increase in Ni concentration around the permalloy composition, and ?s also increases with a decrease in film thickness, in full agreement with previous reports. We extend the technique by demonstrating the technique applied to a multi-layered structure. These results verify the validity of the method and are an important step to facilitate further work in understanding how manipulation of multilayered films can offer tailored magnetostriction.

The buffering effect of hope on clinicians' behavior:A test in pediatric primary care

Although trait hope is thought to motivate goal-directed actions in the face of impediments, few studies have directly examined hope's role in overcoming obstacles, and none have done so while accounting for related goal constructs. We describe a study of 127 pediatric primary care providers who over the course of a year were asked to identify new cases of asthma and confirm previously diagnosed active disease by completing for each of their patients a brief survey validated for this purpose. These clinicians also completed measures of hope, self-efficacy, conscientiousness, and perceived obstacles to implementing a pediatric asthma management program. As predicted by hope theory, the agency component of hope buffered clinicians from perceived obstacles by facilitating the identification of asthma cases among high-hope clinicians in the face of obstacles. This buffering effect remained after controlling for self-efficacy and conscientiousness. We discuss the study findings in terms of current theories of goal-directed behavior and implications for delivering hope-related interventions, and we offer a testable hypothesis regarding when agency and pathways thinking facilitate goal-related behavior.

Organizational Attributes of Practices Successful at a Disease Management Program

Objective: To assess the contribution of organizational factors to implementation of 3 asthma quality measures: enrollment in a disease management program, development of a written treatment plan, and prescription of severity-appropriate anti-inflammatory therapy. Study design: A total of 138 pediatric clinicians and 247 office staff in 13 urban clinics and 23 nonurban private practices completed questionnaires about their practice's organizational characteristics (eg, leadership, communication, perceived effectiveness, job satisfaction). Results: 94% of the clinicians and 92% of the office staff completed questionnaires. When adjusted for confounders, greater practice activity and perceived effectiveness in meeting family needs were associated with higher rates of enrollment in the Easy Breathing program, whereas higher scores for 3 organizational characteristics-communication timeliness, decision authority, and job satisfaction-were associated with both higher enrollment and a greater number of written treatment plans. None of the organizational characteristics was associated with greater use of anti-inflammatory therapy. Conclusions: Three organizational characteristics predicted 2 quality asthma measures: use of a disease management program and creation of a written asthma treatment plan. If these organizational characteristics were amenable to change, then our findings could help focus interventions in areas of effective and acceptable organizational change. © 2009 Mosby, Inc. All rights reserved.