The antiapoptotic RBM5/LUCA-15/H37 gene and its role in apoptosis and human cancer: research update.

The candidate tumour-suppressor gene, LUCA-15/RBM5/H37, maps to the lung cancer tumour-suppressor locus 3p21.3. The LUCA-15 gene locus encodes at least four alternatively spliced transcripts that have been shown to function as regulators of apoptosis, a fact which may have major significance in tumour regulation. This review highlights recent evidence that further implicates the LUCA-15 locus in the control of apoptosis and cell proliferation, and focuses on the observations that confirm the tumour-suppressor activity of this gene

Inhibition of Human T-Cell Proliferation by mTOR antagonists requires Non-Coding RNA growth-arrest-specific transcript 5 (GAS5)

BACKGROUND: Eosinophils are characteristic participants in allergic inflammation. The intracellular signalling mechanisms involved in the migration of eosinophils to sites of allergic inflammation are poorly understood. Chemotactic responses of eosinophils to platelet-activating factor (PAF), but not eotaxin, have been demonstrated to be dependent upon the activation of phosphoinositide 3-kinase (PI3K) but the specific isoform of PI3K involved has not been identified. OBJECTIVE: To determine the roles of the leukocyte-specific PI3K gamma and PI3K delta isoforms of PI3K in PAF-induced chemotaxis of human eosinophils. METHODS: Chemotactic responses of the EoL-1 eosinophilic cell line and human peripheral blood eosinophils were measured. The effects of a PI3K gamma-selective inhibitor (5-[2,2-difluorobenzo(1,3)dioxol-5-ylmethylene]-thiazolidine-2,4-dione; AS604850) and gene knock-down of PI3K gamma and PI3K delta on chemotactic responses were determined. RESULTS: AS604850 caused a concentration-dependent suppression of chemotactic responses of EoL-1 cells and blood eosinophils to PAF but not eotaxin. Specific siRNAs reduced the expression of PI3K gamma and PI3K delta in EoL-1 cells. Knock-down of PI3K gamma by siRNA resulted in a 75% inhibition of the chemotactic response to PAF but had no effect on the response to eotaxin. Knock-down of endogenous PI3K delta by siRNA resulted in a 38% inhibition of the chemotactic response to PAF but had no effect on the response to eotaxin. CONCLUSION: PI3K gamma plays a major role in the induction of chemotaxis in PAF-stimulated eosinophils, while PI3K delta plays a lesser role. Interventions which reduce the activity The central importance of the serine/threonine protein kinase mTOR (mammalian Target of Rapamycin) in the control of cell growth and proliferation is well established. However, our knowledge both of the upstream pathways controlling mTOR activity and of the downstream events mediating these effects is still seriously incomplete. We report a previously unsuspected role for the nonprotein-coding RNA GAS5 in the inhibition of T-cell proliferation produced by mTOR antagonists such as rapamycin. GAS5 transcripts are up-regulated during growth arrest and after rapamycin treatment, and GAS5 has recently been shown to be necessary and sufficient for normal T-cell growth arrest. Down-regulation of GAS5 using RNA interference protects both leukemic and primary human T cells from the inhibition of proliferation produced by mTOR antagonists. The GAS5 transcript is a member of the 5' terminal oligopyrimidine class of RNAs, which is specifically controlled at the level of translation by the mTOR pathway, and the effects of GAS5 on the cell cycle provide a novel and important link to the control of proliferation. These observations point to a significant advance in our understanding of the mechanism of action of mTOR inhibitors, which is likely to lead to improvements in immunosuppressive and cancer therapy

Methane Production from the Pyrolysis–Catalytic Hydrogenation of Waste Biomass: Influence of Process Conditions and Catalyst Type

The production of methane through the optimization of various operating parameters and the use of different catalysts has been investigated using a two-stage, pyrolysis–catalytic hydrogenation reactor. Pyrolysis of the biomass in the first stage produces a suite of gases, including CO2 and CO, which undergo catalytic hydrogenation in the presence of added H2 in the second stage. The influence of the biomass pyrolysis temperature, catalyst temperature, and H2 gas space velocity has been investigated for the optimization and enhancement of the methane yield. In addition, different metal catalysts (Co/Al2O3, Mo/Al2O3, Ni/Al2O3, Fe/Al2O3), the influence of different metal loadings, catalyst calcination temperature, and different support materials (Al2O3, SiO2, and MCM-41) were investigated. The yield of methane was linked to the properties of the catalysts including the preparation calcination temperature and support material which influenced the catalyst surface area and metal crystallite particle size by sintering. The highest methane yield of 7.4 mmol g–1biomass was obtained at a final pyrolysis temperature of 800 °C, catalyst temperature of 500 °C, and H2 gas hourly space velocity of 3600 mL h–1 g–1catayst. This optimization process resulted in 75.5 vol % of methane in the output gaseous mixture

Parametric Study of CO₂ Methanation for Synthetic Natural Gas Production

The production of methane by carbon dioxide hydrogenation through optimization of the operating parameters to enhance methane yield and carbon dioxide conversion in a two‐stage fixed bed reactor is investigated. The influence of temperature, gas hourly space velocity (GHSV), and H2:CO2 ratio on the production of methane is studied. In addition, different methanation catalysts in terms of metal promoters and support materials are investigated to maximize methane production. The results show that the maximum methane yield and maximum carbon dioxide conversion are obtained at a catalyst temperature of 360 °C with a H2:CO2 ratio of 4:1 and total GHSV of 6000 mL h−1 g−1catalyst and reactant GHSV of 3000 mL h−1 g−1catalyst. The optimum metal‐alumina catalyst investigated for CO2 conversion and methane yield is the 10 wt%‐Ni‐Al2O3 catalyst. However, reduction in the methane yield is observed with the addition of Fe and Co promoters because of catalyst sintering and nonuniform dispersion of metals on the support. Among the different catalyst support materials studied, i.e., Al2O3, SiO2 and MCM‐41, the highest catalytic activity is shown by the Al2O3 catalyst with 83 mol% CO2 conversion, producing 81 mol% CH4 with 98% CH4 selectivity

An algorithm for diagnosing IgE-mediated food allergy in study participants who do not undergo food challenge.

BACKGROUND: Food allergy diagnosis in clinical studies can be challenging. Oral food challenges (OFC) are time-consuming, carry some risk and may, therefore, not be acceptable to all study participants. OBJECTIVE: To design and evaluate an algorithm for detecting IgE-mediated food allergy in clinical study participants who do not undergo OFC. METHODS: An algorithm for trial participants in the Barrier Enhancement for Eczema Prevention (BEEP) study who were unwilling or unable to attend OFC was developed. BEEP is a pragmatic, multi-centre, randomized-controlled trial of daily emollient for the first year of life for primary prevention of eczema and food allergy in high-risk infants (ISRCTN21528841). We built on the European iFAAM consensus guidance to develop a novel food allergy diagnosis algorithm using available information on previous allergenic food ingestion, food reaction(s) and sensitization status. This was implemented by a panel of food allergy experts blind to treatment allocation and OFC outcome. We then evaluated the algorithm's performance in both BEEP and Enquiring About Tolerance (EAT) study participants who did undergo OFC. RESULTS: In 31/69 (45%) BEEP and 44/55 (80%) EAT study control group participants who had an OFC the panel felt confident enough to categorize children as "probable food allergy" or "probable no food allergy". Algorithm-derived panel decisions showed high sensitivity 94% (95%CI 68, 100) BEEP; 90% (95%CI 72, 97) EAT and moderate specificity 67% (95%CI 39, 87) BEEP; 67% (95%CI 39, 87) EAT. Sensitivity and specificity were similar when all BEEP and EAT participants with OFC outcome were included. CONCLUSION: We describe a new algorithm with high sensitivity for IgE-mediated food allergy in clinical study participants who do not undergo OFC. CLINICAL RELEVANCE: This may be a useful tool for excluding food allergy in future clinical studies where OFC is not conducted

A study of general practitioners' perspectives on electronic medical records systems in NHS Scotland

<b>Background</b> Primary care doctors in NHSScotland have been using electronic medical records within their practices routinely for many years. The Scottish Health Executive eHealth strategy (2008-2011) has recently brought radical changes to the primary care computing landscape in Scotland: an information system (GPASS) which was provided free-of-charge by NHSScotland to a majority of GP practices has now been replaced by systems provided by two approved commercial providers. The transition to new electronic medical records had to be completed nationally across all health-boards by March 2012. <p></p><b> Methods</b> We carried out 25 in-depth semi-structured interviews with primary care doctors to elucidate GPs' perspectives on their practice information systems and collect more general information on management processes in the patient surgical pathway in NHSScotland. We undertook a thematic analysis of interviewees' responses, using Normalisation Process Theory as the underpinning conceptual framework. <p></p> <b>Results</b> The majority of GPs' interviewed considered that electronic medical records are an integral and essential element of their work during the consultation, playing a key role in facilitating integrated and continuity of care for patients and making clinical information more accessible. However, GPs expressed a number of reservations about various system functionalities - for example: in relation to usability, system navigation and information visualisation. <b>Conclusion </b>Our study highlights that while electronic information systems are perceived as having important benefits, there remains substantial scope to improve GPs' interaction and overall satisfaction with these systems. Iterative user-centred improvements combined with additional training in the use of technology would promote an increased understanding, familiarity and command of the range of functionalities of electronic medical records among primary care doctors

Midday measurements of leaf water potential and stomatal conductance are highly correlated with daily water use of Thompson Seedless grapevines

A study was conducted to determine the relationship between midday measurements of vine water status and daily water use of grapevines measured with a weighing lysimeter. Water applications to the vines were terminated on August 24th for 9 days and again on September 14th for 22 days. Daily water use of the vines in the lysimeter (ETLYS) was approximately 40 L vine−1 (5.3 mm) prior to turning the pump off, and it decreased to 22.3 L vine−1 by September 2nd. Pre-dawn leaf water potential (ΨPD) and midday Ψl on August 24th were −0.075 and −0.76 MPa, respectively, with midday Ψl decreasing to −1.28 MPa on September 2nd. Leaf g s decreased from ~500 to ~200 mmol m−2 s−1 during the two dry-down periods. Midday measurements of g s and Ψl were significantly correlated with one another (r = 0.96) and both with ETLYS/ETo (r = ~0.9). The decreases in Ψl, g s, and ETLYS/ETo in this study were also a linear function of the decrease in volumetric soil water content. The results indicate that even modest water stress can greatly reduce grapevine water use and that short-term measures of vine water status taken at midday are a reflection of daily grapevine water us

Mental practice with interactive 3D visual aids enhances surgical performance

Background: Evidence suggests that Mental Practice (MP) could be used to finesse surgical skills. However, MP is cognitively demanding and may be dependent on the ability of individuals to produce mental images. In this study, we hypothesised that the provision of interactive 3D visual aids during MP could facilitate surgical skill performance. Methods: 20 surgical trainees were case-matched to one of three different preparation methods prior to performing a simulated Laparoscopic Cholecystectomy (LC). Two intervention groups underwent a 25-minute MP session; one with interactive 3D visual aids depicting the relevant surgical anatomy (3D-MP group, n = 5) and one without (MP-Only, n = 5). A control group (n = 10) watched a didactic video of a real LC. Scores relating to technical performance and safety were recorded by a surgical simulator. Results: The Control group took longer to complete the procedure relative to the 3D&MP condition (p = .002). The number of movements was also statistically different across groups (p = .001), with the 3D&MP group making fewer movements relative to controls (p = .001). Likewise, the control group moved further in comparison to the 3D&MP condition and the MP-Only condition (p = .004). No reliable differences were observed for safety metrics. Conclusion: These data provide evidence for the potential value of MP in improving performance. Furthermore, they suggest that 3D interactive visual aids during MP could potentially enhance performance, beyond the benefits of MP alone. These findings pave the way for future RCTs on surgical preparation and performance