Hypoxia and hyperglycaemia determine why some endometrial tumours fail to respond to metformin

High expression of Ki67, a proliferation marker, is associated with reduced endometrial cancer-specific survival. Pre-surgical metformin reduces tumour Ki-67 expression in some women with endometrial cancer. Metformin's anti-cancer activity may relate to effects on cellular energy metabolism. Since tumour hypoxia and glucose availability are major cellular redox determinants, we evaluated their role in endometrial cancer response to metformin. Endometrial cancer biopsies from women treated with pre-surgical metformin were tested for the hypoxia markers, HIF-1α and CA-9. Endometrial cancer cell lines were treated with metformin in variable glucose concentrations in normoxia or hypoxia and cell viability, mitochondrial biogenesis, function and energy metabolism were assessed. In women treated with metformin (n = 28), Ki-67 response was lower in hypoxic tumours. Metformin showed minimal cytostatic effects towards Ishikawa and HEC1A cells in conventional medium (25 mM glucose). In low glucose (5.5 mM), a dose-dependent cytostatic effect was observed in normoxia but attenuated in hypoxia. Tumours treated with metformin showed increased mitochondrial mass (n = 25), while in cultured cells metformin decreased mitochondrial function. Metformin targets mitochondrial respiration, however, in hypoxic, high glucose conditions, there was a switch to glycolytic metabolism and decreased metformin response. Understanding the metabolic adaptations of endometrial tumours may identify patients likely to derive clinical benefit from metformin

Observational evidence for the convective transport of dust over the central United States

Bulk aerosol composition and aerosol size distributions measured aboard the DC-8 aircraft during the Deep Convective Clouds and Chemistry Experiment mission in May/June 2012 were used to investigate the transport of mineral dust through nine storms encountered over Colorado and Oklahoma. Measurements made at low altitudes (\u3c5 km mean sea level (MSL)) in the storm inflow region were compared to those made in cirrus anvils (altitude \u3e 9 km MSL). Storm mean outflow Ca2+ mass concentrations and total coarse (1 µm \u3c diameter \u3c 5 µm) aerosol volume (Vc) were comparable to mean inflow values as demonstrated by average outflow/inflow ratios greater than 0.5. A positive relationship between Ca2+, Vc, ice water content, and large (diameter \u3e 50 µm) ice particle number concentrations was not evident; thus, the influence of ice shatter on these measurements was assumed small. Mean inflow aerosol number concentrations calculated over a diameter range (0.5 µm \u3c diameter \u3c 5.0 µm) relevant for proxy ice nuclei (NPIN) were ~15–300 times higher than ice particle concentrations for all storms. Ratios of predicted interstitial NPIN (calculated as the difference between inflow NPIN and ice particle concentrations) and inflow NPIN were consistent with those calculated for Ca2+ and Vc and indicated that on average less than 10% of the ingested NPIN were activated as ice nuclei during anvil formation. Deep convection may therefore represent an efficient transport mechanism for dust to the upper troposphere where these particles can function as ice nuclei cirrus forming in situ

Climatic controls on diffuse groundwater recharge across Australia

Reviews of field studies of groundwater recharge have attempted to investigate how climate characteristics control recharge, but due to a lack of data have not been able to draw any strong conclusions beyond that rainfall is the major determinant. This study has used numerical modelling for a range of Köppen-Geiger climate types (tropical, arid and temperate) to investigate the effect of climate variables on recharge for different soil and vegetation types. For the majority of climate types, the correlation between the modelled recharge and total annual rainfall is weaker than the correlation between recharge and the annual rainfall parameters reflecting rainfall intensity. Under similar soil and vegetation conditions for the same annual rainfall, annual recharge in regions with winter-dominated rainfall is greater than in regions with summer-dominated rainfall. The importance of climate parameters other than rainfall in recharge estimation is highest in the tropical climate type. Mean annual values of solar radiation and vapour pressure deficit show a greater importance in recharge estimation than mean annual values of the daily mean temperature. Climate parameters have the lowest relative importance in recharge estimation in the arid climate type (with cold winters) and the temperate climate type. For 75% of all soil, vegetation and climate types investigated, recharge elasticity varies between 2 and 4 indicating a 20% to 40% change in recharge for a 10% change in annual rainfall. Understanding how climate controls recharge under the observed historical climate allows more informed choices of analogue sites if they are to be used for climate change impact assessments

Energy Dependence of Nuclear Transparency in C(p,2p) Scattering

The transparency of carbon for (p,2p) quasi-elastic events was measured at beam energies ranging from 6 to 14.5 GeV at 90 degrees c.m. The four momentum transfer squared q*q ranged from 4.8 to 16.9 (GeV/c)**2. We present the observed energy dependence of the ratio of the carbon to hydrogen cross sections. We also apply a model for the nuclear momentum distribution of carbon to normalize this transparency ratio. We find a sharp rise in transparency as the beam energy is increased to 9 GeV and a reduction to approximately the Glauber level at higher energies.Comment: 4 pages, 2figures, submitted to PR

Phenotypic spectrum associated with de novo and inherited deletions and duplications at 16p11.2 in individuals ascertained for diagnosis of autism spectrum disorder

Background Recurrent microdeletions and microduplications of w555 kb at 16p11.2 confer susceptibility to autism spectrum disorder (ASD) in up to 1% of ASD patients. No physical or behavioural features have been identified that distinguish these individuals as having a distinct ASD subtype, but clinical data are limited. Methods We report five autistic probands identified by microarray analysis with copy number variation (CNV) of 16p11.2 (three deletions, two duplications). Each patient was assessed for ASD and dysmorphic features. We also describe a deletion positive 26-month-old female who has developmental delay (DD) and autistic features. Results Proband 1 (female with ASD, de novo deletion) is not dysmorphic. Proband 2 (male with autism, de novo deletion) and proband 3 and his brother (males with autism, inherited deletions) are dysmorphic, but the two probands do not resemble one another. The mother of proband 3 has mild mental retardation (MR), minor dysmorphism and meets the criteria for ASD. Proband 4 (dysmorphic autistic male, de novo duplication) had a congenital diaphragmatic hernia. Proband 5 (nondysmorphic ASD female with a duplication) has two apparently healthy duplication positive relatives. Probands 1 and 2 have deletion negative siblings with ASD and Asperger syndrome, respectively. Proband 6 (a female with DD and an inherited duplication) is dysmorphic, but has oligohydramnios sequence. Conclusions The phenotypic spectrum associated with CNV at 16p11.2 includes ASD, MR/DD and/or possibly other primary psychiatric disorders. Compared with the microduplications, the reciprocal microdeletions are more likely to be penetrant and to be associated with nonspecific major or minor dysmorphism. There are deletion positive ASD probands with a less severe phenotype than deletion negative ASD siblings underscoring the significant phenotypic heterogeneity.published_or_final_versio

Increasing protein content of wheat by breeding

The most efficient means of increasing protein content of WesternAustralian wheat is by breeding new varieties with higher inherent protein in their grain. But is this possible without sacrificing yeild or other desirable characteristics

Q2Q^2 Independence of QF2/F1QF_2/F_1, Poincare Invariance and the Non-Conservation of Helicity

A relativistic constituent quark model is found to reproduce the recent data regarding the ratio of proton form factors, $F_2(Q^2)/F_1(Q^2)$. We show that imposing Poincare invariance leads to substantial violation of the helicity conservation rule, as well as an analytic result that the ratio $F_2(Q^2)/F_1(Q^2)\sim 1/Q$ for intermediate values of $Q^2$.Comment: 13 pages, 7 figures, to be submitted to Phys. Rev. C typos corrected, references added, 1 new figure to show very high Q^2 behavio

Comparison of embedded and added motor imagery training in patients after stroke: Study protocol of a randomised controlled pilot trial using a mixed methods approach

Copyright @ 2009 Schuster et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Two different approaches have been adopted when applying motor imagery (MI) to stroke patients. MI can be conducted either added to conventional physiotherapy or integrated within therapy sessions. The proposed study aims to compare the efficacy of embedded MI to an added MI intervention. Evidence from pilot studies reported in the literature suggests that both approaches can improve performance of a complex motor skill involving whole body movements, however, it remains to be demonstrated, which is the more effective one.Methods/Design: A single blinded, randomised controlled trial (RCT) with a pre-post intervention design will be carried out. The study design includes two experimental groups and a control group (CG). Both experimental groups (EG1, EG2) will receive physical practice of a clinical relevant motor task ('Going down, laying on the floor, and getting up again') over a two week intervention period: EG1 with embedded MI training, EG2 with MI training added after physiotherapy. The CG will receive standard physiotherapy intervention and an additional control intervention not related to MI.The primary study outcome is the time difference to perform the task from pre to post-intervention. Secondary outcomes include level of help needed, stages of motor task completion, degree of motor impairment, balance ability, fear of falling measure, motivation score, and motor imagery ability score. Four data collection points are proposed: twice during baseline phase, once following the intervention period, and once after a two week follow up. A nested qualitative part should add an important insight into patients' experience and attitudes towards MI. Semi-structured interviews of six to ten patients, who participate in the RCT, will be conducted to investigate patients' previous experience with MI and their expectations towards the MI intervention in the study. Patients will be interviewed prior and after the intervention period.Discussion: Results will determine whether embedded MI is superior to added MI. Findings of the semi-structured interviews will help to integrate patient's expectations of MI interventions in the design of research studies to improve practical applicability using MI as an adjunct therapy technique

Substantial Seasonal Contribution of Observed Biogenic Sulfate Particles to Cloud Condensation Nuclei

Biogenic sources contribute to cloud condensation nuclei (CCN) in the clean marine atmosphere, but few measurements exist to constrain climate model simulations of their importance. The chemical composition of individual atmospheric aerosol particles showed two types of sulfate-containing particles in clean marine air masses in addition to mass-based Estimated Salt particles. Both types of sulfate particles lack combustion tracers and correlate, for some conditions, to atmospheric or seawater dimethyl sulfide (DMS) concentrations, which means their source was largely biogenic. The first type is identified as New Sulfate because their large sulfate mass fraction (63% sulfate) and association with entrainment conditions means they could have formed by nucleation in the free troposphere. The second type is Added Sulfate particles (38% sulfate), because they are preexisting particles onto which additional sulfate condensed. New Sulfate particles accounted for 31% (7 cm−3) and 33% (36 cm−3) CCN at 0.1% supersaturation in late-autumn and late-spring, respectively, whereas sea spray provided 55% (13 cm−3) in late-autumn but only 4% (4 cm−3) in late-spring. Our results show a clear seasonal difference in the marine CCN budget, which illustrates how important phytoplankton-produced DMS emissions are for CCN in the North Atlantic