Membrane-bound β-catenin degradation is enhanced by ETS2-mediated Siah1 induction in Helicobacter pylori-infected gastric cancer cells.

β-catenin has two different cellular functions: intercellular adhesion and transcriptional activity. The E3 ubiquitin ligase Siah1 causes ubiquitin-mediated degradation of the cytosolic β-catenin and therefore, impairs nuclear translocation and oncogenic function of β-catenin. However, the effect of Siah1 on the cell membrane bound β-catenin has not been studied. In this study, we identified that the carcinogenic bacterium H. pylori increased ETS2 transcription factor-mediated Siah1 protein expression in gastric cancer cells (GCCs) MKN45, AGS and Kato III. Siah1 protein level was also noticeably higher in gastric adenocarcinoma biopsy samples as compared to non-cancerous gastric epithelia. Siah1 knockdown significantly decreased invasiveness and migration of H. pylori-infected GCCs. Although, Siah1 could not increase degradation of the cytosolic β-catenin and its nuclear translocation, it enhanced degradation of the membrane-bound β-catenin in the infected GCCs. This loss of membrane-bound pool of β-catenin was not associated with the proteasomal degradation of E-cadherin. Thus, this work delineated the role of Siah1 in increasing invasiveness of H. pylori-infected GCCs

A polarized atomic hydrogen beam

We describe the design and operating characteristics of a simple polarized atomic hydrogen beam particularly suitable for applications to crossed beams experiments. In addition to experimental measurements, we present the results of detailed computer models, using Monte-Carlo ray tracing techniques, optical analogs, and phase-space methods, that not only provide us with a confirmation of our measurement, but also allow us to characterize the density, polarization, and atomic fraction of the beam at all points along its path. As a subsidiary result, we also present measurements of the relative and absolute efficiencies of the V/G Supavac mass analyzer for masses 1 and 2

Components of good end of life care within the paediatric intensive care setting – an online survey

BACKGROUND This study was undertaken to better understand the components of good end of life for children who are being cared for within the PICU. Cure rates from serious childhood illness are gradually improving every year. Despite this, there are still a small but significant number of children who will die within a Paediatric Intensive Care Unit. OBJECTIVES 1. The primary objective was to determine what the key aspects of End-of-Life-Care/palliative care in PICU as perceived by Health Professionals (including General Paediatricians) 2. This project will result in a schema of components of care which can be used by health professionals within in the intensive care setting to assist with excellent end of life care. METHOD An online survey of health professionals was used to rank various components of palliative care within the PICU context. Survey participants could also suggest other components of care that had not already been thought of within the survey. RESULTS There were 108 respondents who took the survey. The survey group were multidisciplinary (medical 32.4%; nursing 44.44% and allied health 23.15 %). There were also a variety of specialties represented in the survey (PICU 56.5 %; Paediatric Palliative Care 17.4%; General Paediatrics 13.9% and Other 12.2 %). The top 5 components of care ranked by the group included were identified by the interest groups after being ranked according to their importance. These included 1. Discussion of a Management Plan 2. Sensitive, compassionate use of language 3. Discussion of End of Life care 4. Discussion of anticipated changes in the patient's condition 5. Discussion of the caregiver's understanding of the illness. CONCLUSION It is hoped that the schema for good end of life care represents a consensus from a large and diverse group of health professionals. This schema should assist in the day to day care of patients. Further, it should also be of benefit in education, research and quality activities

Characterization of Histone Modifications in Late-Stage Rotator Cuff Tendinopathy

The development and progression of rotator cuff tendinopathy (RCT) is multifactorial and likely to manifest through a combination of extrinsic, intrinsic, and environmental factors, including genetics and epigenetics. However, the role of epigenetics in RCT, including the role of histone modification, is not well established. Using chromatin immunoprecipitation sequencing, differences in the trimethylation status of H3K4 and H3K27 histones in late-stage RCT compared to control were investigated in this study. For H3K4, 24 genomic loci were found to be significantly more trimethylated in RCT compared to control (p < 0.05), implicating genes such as DKK2, JAG2, and SMOC2 in RCT. For H3K27, 31 loci were shown to be more trimethylated (p < 0.05) in RCT compared to control, inferring a role for EPHA3, ROCK1, and DEFβ115. Furthermore, 14 loci were significantly less trimethylated (p < 0.05) in control compared to RCT, implicating EFNA5, GDF6, and GDF7. Finally, the TGFβ signaling, axon guidance, and regulation of focal adhesion assembly pathways were found to be enriched in RCT. These findings suggest that the development and progression of RCT is, at least in part, under epigenetic control, highlighting the influence of histone modifications in this disorder and paving the way to further understand the role of epigenome in RCT

Transition phenomena in unstably stratified turbulent flows

We study experimentally and theoretically transition phenomena caused by the external forcing from Rayleigh-Benard convection with the large-scale circulation (LSC) to the limiting regime of unstably stratified turbulent flow without LSC whereby the temperature field behaves like a passive scalar. In the experiments we use the Rayleigh-B\'enard apparatus with an additional source of turbulence produced by two oscillating grids located nearby the side walls of the chamber. When the frequency of the grid oscillations is larger than 2 Hz, the large-scale circulation (LSC) in turbulent convection is destroyed, and the destruction of the LSC is accompanied by a strong change of the mean temperature distribution. However, in all regimes of the unstably stratified turbulent flow the ratio $\big[(\ell_x \nabla_x T)^2 + (\ell_y \nabla_y T)^2 + (\ell_z \nabla_z T)^2\big] /$ varies slightly (even in the range of parameters whereby the behaviour of the temperature field is different from that of the passive scalar). Here $\ell_i$ are the integral scales of turbulence along x, y, z directions, T and \theta are the mean and fluctuating parts of the fluid temperature. At all frequencies of the grid oscillations we have detected the long-term nonlinear oscillations of the mean temperature. The theoretical predictions based on the budget equations for turbulent kinetic energy, turbulent temperature fluctuations and turbulent heat flux, are in agreement with the experimental results.Comment: 14 pages, 14 figures, REVTEX4-1, revised versio

Forehead reflectance photoplethysmography to monitor heart rate: preliminary results from neonatal patients

Around 5%–10% of newborn babies require some form of resuscitation at birth and heart rate (HR) is the best guide of efficacy. We report the development and first trial of a device that continuously monitors neonatal HR, with a view to deployment in the delivery room to guide newborn resuscitation. The device uses forehead reflectance photoplethysmography (PPG) with modulated light and lock-in detection. Forehead fixation has numerous advantages including ease of sensor placement, whilst perfusion at the forehead is better maintained in comparison to the extremities. Green light (525 nm) was used, in preference to the more usual red or infrared wavelengths, to optimize the amplitude of the pulsatile signal. Experimental results are presented showing simultaneous PPG and electrocardiogram (ECG) HRs from babies (n = 77), gestational age 26–42 weeks, on a neonatal intensive care unit. In babies ≥32 weeks gestation, the median reliability was 97.7% at ±10 bpm and the limits of agreement (LOA) between PPG and ECG were +8.39 bpm and −8.39 bpm. In babies <32 weeks gestation, the median reliability was 94.8% at ±10 bpm and the LOA were +11.53 bpm and −12.01 bpm. Clinical evaluation during newborn deliveries is now underway

Two-year long safety and efficacy of deferasirox film-coated tablets in patients with thalassemia or lower/intermediate risk MDS: phase 3 results from a subset of patients previously treated with deferasirox in the ECLIPSE study

Background: Despite the proven benefits of iron chelation therapy (ICT) in the management of chronic iron overload and related complications, compliance to long-term ICT is challenging. Results from the ECLIPSE study, an open-label, randomized, multicenter, 2-arm, phase 2 study evaluated the safety of deferasirox dispersible tablet and film-coated tablet (FCT) formulations in patients with transfusion-dependent thalassemia (TDT) or very low, low, or intermediate risk myelodysplastic syndrome (MDS) treated over 24 weeks. Methods: The aim of the current study (a 2-year, open-label, multicenter, single-arm, phase 3 study) is to evaluate the long-term safety and efficacy of deferasirox FCT in a subset of patients with TDT or lower/intermediate-risk MDS treated for 2 years after the completion of 24 weeks of treatment with deferasirox in the ECLIPSE phase 2 study. Results: Of 53 patients enrolled, 34 (64.2%) completed treatment and study. Adverse events (AEs) reported in most patients (similar to 70%) were of mild to moderate severity. Headache and diarrhea were the most frequently (&gt; 25%) reported AEs. None of the serious AEs (including 1 death) were considered treatment related. No new safety signal was identified, and long-term safety of deferasirox FCT was consistent with the known safety profile of deferasirox. No major concerns associated with gastrointestinal tolerability, renal safety, or hematological abnormalities (thrombocytopenia/neutropenia) were reported during the 2 years. Patients receiving deferasirox FCT had a treatment compliance (by pill count) of similar to 90% and persistence (continuous use for &gt;= 30 days) of &gt; 95%. Reduction in serum ferritin level was almost consistent starting from week 2 across all post-baseline time points (relative reduction: month 6, 19%; month 12, 29%). Conclusions: The results from this 2-year interventional study suggest that the recommended dosing of deferasirox FCT, with better tolerability, palatability, and compliance, offers a favorable option of ICT for long-term management of iron overload and associated complications in TDT

Bubbly two-phase flow in hydraulic jumps at large Froude numbers

A hydraulic jump is a sudden, rapid transition from a supercritical flow to a subcritical flow. At large inflow Froude numbers, the jump is characterized by a significant amount of entrained air. For this paper, the bubbly two-phase flow properties of steady and strong hydraulic jumps were investigated experimentally. The results demonstrate that the strong air entrainment rate and the depth-averaged void-fraction data highlight a rapid deaeration of the jump roller. The results suggest that the hydraulic jumps are effective aerators and that the rate of detrainment is comparatively smaller at the largest Froude numbers. © 2011 American Society of Civil Engineers