Mitoparans: mitochondriotoxic cell penetrating peptides and novel inducers of apoptosis.

Acknowledgments The authors would like to thank Keith Holding at the University of Wolverhampton for his outstanding technical support. This work was supported in part by Samantha Dickson Brain Tumour Trust.Introduction: The amphipathic helical peptide mastoparan (MP; H-INLKALAALAKKIL-NH2) inserts into biological membranes to modulate the activity of heterotrimeric G proteins and other targets. Moreover, whilst cell free models of apoptosis demonstrate MP to facilitate mitochondrial permeability transition and release of apoptogenic cytochrome c, MP-induced death of intact cells has been attributed to its non-specific membrane destabilising properties (necrotic mechanisms). However, MP and related peptides are known to activate other signalling systems, including p42/p44 MAP kinases and could therefore, also modulate cell fate and specific apoptotic events. The ability of MP to facilitate mitochondrial permeability in cell free systems has lead to proposals that MP could be of utility in tumour therapeutics provided that it conferred features of cellular penetration and mitochondrial localization. We have recently reported that our highly potent amphipathic MP analogue mitoparan (mitP; [Lys5,8Aib10]MP; Aib = -aminoisobutyric acid) specifically promotes apoptosis of human cancer cells, as was confirmed by in situ TUNEL staining and activation of caspase-3. Moreover, we have also demonstrated that mitP penetrates plasma membranes and redistributes to co-localize with mitochondria. Complementary studies, using isolated mitochondria, further demonstrated that mitP, through co-operation with a protein of the permeability transition pore complex voltage-dependent anion channel (VDAC), induced swelling and permeabilization of mitochondria, leading to the release of the apoptogenic factor cytochrome c. An expanding field of peptide and cell penetrating peptide (CPP) research has focussed on the selective targeting of tumours by engineering constructs that incorporate cell-specific or tissue–specific address motifs. Peptidyl address motifs could enhance the selectivity of drug delivery whilst the improved cellular uptake offered by CPP enhances bioavailability. Thus and as a potential therapeutic strategy, we extended our findings to design target-specific mitP analogues. The integrin-specific address motif RGD and a Fas ligand mimetic WEWT were incorporated by N-terminal acylation of mitP to produce novel tandem-linked chimeric peptides

Resilient Microgrid Energy Management Algorithm Based on Distributed Optimization

This article proposes a fully distributed energy management algorithm for dc microgrids, resilient to different faults. Specifically, we employ distributed model-predictive control to deal with the uncertainty that characterizes the microgrid operation. The optimization problem is solved at each time step through a distributed optimization algorithm, which has three main advantages: 1) agents of the network require a small computational power; 2) local information is not shared among the network nodes, hence preserving a certain level of privacy; and 3) it is suitable for implementation in large-scale systems. The resilience property of the algorithm stems from additional constraints that are enforced in order to store in the system enough energy to sustain the microgrid in the case of utility grid or line fault. Simulation results show that the algorithm is suitable to schedule the operation of agents that are always connected to the microgrid (e.g., loads) as well as agents that may be connected and disconnected (e.g., electric vehicles)

NADINE GORDIMER’S “NOT FOR PUBLICATION” AND POST-COLONIAL POLITICAL POWER DURING THE APARTHEID REGIME

Analisa-se o conto “Not for publication” (1965), da escritora sulafricanaNadine Gordimer, pela crítica pós-colonial. Os trabalhos literários deGordimer denunciam e criticam o colonialismo e suas conseqüências no contextodo regime do apartheid. O texto retrata o poder do discurso colonial e desmascaraas falsas (às vezes bem-intencionadas) intenções dos colonizadoresreferentes ao sujeito colonial representado por Praise Basetse. O pobre meninonegro, manipulado por colonizadores que dedicaram suas vidas aos negros, éfabricado para que o poder deles continue dominante no país. Praise enfrenta anecessidade e as dificuldades inerentes à resistência contra a situação. Suarebelião revela que o discurso colonial pode ser subvertido. Os resultados mostramas estratégias que os colonizadores empregam para perpetuar o poder nacolônia e, ao mesmo tempo, a conscientização gradual e silenciosa dos sujeitoscoloniais contra os impedimentos postos a sua autonomia e a sua subjetividade.Palavras-chave: pós-colonialismo; Gordimer; apartheid; resistência; estratégias

DORIS LESSING’S “LITTLE TEMBI” AND POST-COLONIAL CRITICISM

Colonial strategies, including degradation and the othering of the colonial subject are analyzed in the short story “Little Tembi” by Doris Lessing. The manner an African boy is othered by white plantation owners and his resistance against the colonial and apartheid system through sly civility and crime are investigated

Associations between quality indicators of internal medicine residency training programs

<p>Abstract</p> <p>Background</p> <p>Several residency program characteristics have been suggested as measures of program quality, but associations between these measures are unknown. We set out to determine associations between these potential measures of program quality.</p> <p>Methods</p> <p>Survey of internal medicine residency programs that shared an online ambulatory curriculum on hospital type, faculty size, number of trainees, proportion of international medical graduate (IMG) trainees, Internal Medicine In-Training Examination (IM-ITE) scores, three-year American Board of Internal Medicine Certifying Examination (ABIM-CE) first-try pass rates, Residency Review Committee-Internal Medicine (RRC-IM) certification length, program director clinical duties, and use of pharmaceutical funding to support education. Associations assessed using Chi-square, Spearman rank correlation, univariate and multivariable linear regression.</p> <p>Results</p> <p>Fifty one of 67 programs responded (response rate 76.1%), including 29 (56.9%) community teaching and 17 (33.3%) university hospitals, with a mean of 68 trainees and 101 faculty. Forty four percent of trainees were IMGs. The average post-graduate year (PGY)-2 IM-ITE raw score was 63.1, which was 66.8 for PGY3s. Average 3-year ABIM-CE pass rate was 95.8%; average RRC-IM certification was 4.3 years. ABIM-CE results, IM-ITE results, and length of RRC-IM certification were strongly associated with each other (p < 0.05). PGY3 IM-ITE scores were higher in programs with more IMGs and in programs that accepted pharmaceutical support (p < 0.05). RRC-IM certification was shorter in programs with higher numbers of IMGs. In multivariable analysis, a higher proportion of IMGs was associated with 1.17 years shorter RRC accreditation.</p> <p>Conclusions</p> <p>Associations between quality indicators are complex, but suggest that the presence of IMGs is associated with better performance on standardized tests but decreased duration of RRC-IM certification.</p

Macronutrient Intake, Diagnosis Status, and Glycemic Control Among US Hispanics/Latinos With Diabetes

CONTEXT: Diet modification is a mainstay of diabetes management. US Hispanics/Latinos are disproportionately affected by diabetes, but few studies have examined dietary intake among US Hispanics/Latinos with diabetes, and little is known regarding the influence of diabetes awareness on dietary intake. OBJECTIVE: We evaluated macronutrient intake and its associations with diabetes awareness and glycemic control among US Hispanics/Latinos with diabetes. PARTICIPANTS: This analysis included 3310 diabetic adults aged 18–74 years from the Hispanic Community Health Study/Study of Latinos (2008–2011). MAIN OUTCOME MEASURES: Diabetes was defined as diagnosed (based on medical history or antihyperglycemic medication use) or undiagnosed diabetes (based on fasting glucose ≥ 126 mg/dL, glycated hemoglobin [HbA1c] ≥ 6.5%, or 2 h glucose ≥ 200 mg/dL in the absence of a physician diagnosis). Dietary intake was assessed using two 24-hour recalls. RESULTS: Among Hispanic/Latino adults with diabetes, 21.2%, 55.7%, and 71.2% met the American Diabetes Association recommendations for fiber (≥14 g per 1000 kcal), saturated fat (<10% of total energy), and cholesterol intake (<300 mg), respectively. Compared with those with undiagnosed diabetes, people with diagnosed diabetes consumed less carbohydrate (50.3 vs 52.4% of total energy; P = .017), total sugar (19.1 vs 21.5% of total energy; P = .002), added sugar (9.8 vs 12.1% of total energy; P < .001), and more total fat (30.7 vs 29.3% of total energy; P = .048) and monounsaturated fat (11.5 vs 10.7% of total energy; P = .021). Association between diabetes awareness and low total and added sugar intake was observed in individuals of Mexican and Puerto Rican background but not in other groups (P for interaction < .05). Among people with diagnosed diabetes, those with HbA1c of 7% or greater consumed more total fat, saturated fat, and cholesterol than those with HbA1c less than 7% (all P < .05). CONCLUSIONS: Among US Hispanics/Latinos with diabetes, fiber intake is low, and diabetes awareness is associated with reduced carbohydrate and sugar intake and increased monounsaturated fat intake. Sugar intake may require special attention in certain Hispanic/Latino background groups

The GALAH survey: Stellar streams and how stellar velocity distributions vary with Galactic longitude, hemisphere, and metallicity

Using GALAH (GALactic Archaeology with HERMES) survey data of nearby stars, we look at how structure in the planar (u, v) velocity distribution depends on metallicity and on viewing direction within the Galaxy. In nearby stars with distance d≲1 kpc, the Hercules stream is most strongly seen in higher metallicity stars [Fe/H] > 0.2. The Hercules stream peak v value depends on viewed galactic longitude, which we interpret as due to the gap between the stellar stream and more circular orbits being associated with a specific angular momentum value of about 1640 km s−1 kpc. The association of the gap with a particular angular momentum value supports a bar resonant model for the Hercules stream. Moving groups previously identified in Hipparcos(HIgh Precision Parallax COllecting Satellite) observations are easiest to see in stars nearer than 250 pc, and their visibility and peak velocities in the velocity distributions depends on both viewing direction (galactic longitude and hemisphere) and metallicity. We infer that there is fine structure in local velocity distributions that varies over distances of a few hundred pc in the Galaxy.Parts of this research were conducted by the Australian Research Council (ARC) Centre of Excellence for All Sky Astrophysics in 3 Dimensions (ASTRO 3D), through project number CE170100013. JB-H acknowledges a Miller Professorship from the Miller Institute, UC Berkeley, and an ARC Laureate Fellowship which also supports GDS and SS. SM acknowledges support from the ARC through DECRA Fellowship DE140100598. JK is supported by an ARC DP grant awarded to JB-H and TB. MH is supported by ASTRO 3D Centre of Excellence funding to the University of Sydney and an ARC DP grant awarded to KF. LD gratefully acknowledges a scholarship from Zonta International District 24. LD and KF acknowledge support from ARC grant DP160103747. LC is the recipient of an ARC Future Fellowship (project number FT160100402)

The GALAH Survey: Lithium-strong KM dwarfs

Identifying and characterizing young stars in the Solar neighbourhood is essential to find and describe planets in the early stages of their evolution. This work seeks to identify nearby young stars showing a lithium 6708 Å absorption line in the GALAH survey. A robust, data-driven approach is used to search for corresponding templates in the pool of 434 215 measured dwarf spectra in the survey. It enables a model-free search for best-matching spectral templates for all stars, including M dwarfs with strong molecular absorption bands. 3147 stars have been found to have measurable lithium: 1408 G and 892 K0–K5 dwarfs (EW(Li) > 0.1 Å), 335 K5–K9 (>0.07 Å) and 512 M0–M4 dwarfs (>0.05 Å). Stars with such lithium features are used to investigate the possibility of searching for young stars above the main sequence based merely on their parallaxes and broad-band photometry. The selection of young stars above the main sequence is highly effective for M dwarfs, moderately effective for K dwarfs and ineffective for G dwarfs. Using a combination of the lithium information and the complete 6D kinematics from Gaia and GALAH, 305 new candidate moving group members have been found, 123 of which belong to the Scorpius–Centaurus association, 36 to the Pleiades and 25 to the Hyades clusters.Funding for the DPAC has been provided by national institutions, in particular the institutions participating in the Gaia Multilateral Agreement. M Z acknowledges funding from the Australian Research Council (grant DP170102233). TN acknowledges funding from the Australian Research Council (grant DP150100250). TZ and KC acknowledge financial support of the Slovenian Research Agency (research core funding No. P1-0188 and project N1-0040). SB acknowledges funds from the Alexander von Humboldt Foundation in the framework of the Sofja Kovalevskaja Award endowed by the Federal Ministry of Education and Research

Stellar Astrophysics and Exoplanet Science with the Maunakea Spectroscopic Explorer (MSE)

The Maunakea Spectroscopic Explorer (MSE) is a planned 11.25-m aperture facility with a 1.5 square degree field of view that will be fully dedicated to multi-object spectroscopy. A rebirth of the 3.6m Canada-France-Hawaii Telescope on Maunakea, MSE will use 4332 fibers operating at three different resolving powers (R ~ 2500, 6000, 40000) across a wavelength range of 0.36-1.8mum, with dynamical fiber positioning that allows fibers to match the exposure times of individual objects. MSE will enable spectroscopic surveys with unprecedented scale and sensitivity by collecting millions of spectra per year down to limiting magnitudes of g ~ 20-24 mag, with a nominal velocity precision of ~100 m/s in high-resolution mode. This white paper describes science cases for stellar astrophysics and exoplanet science using MSE, including the discovery and atmospheric characterization of exoplanets and substellar objects, stellar physics with star clusters, asteroseismology of solar-like oscillators and opacity-driven pulsators, studies of stellar rotation, activity, and multiplicity, as well as the chemical characterization of AGB and extremely metal-poor stars.Comment: 31 pages, 11 figures; To appear as a chapter for the Detailed Science Case of the Maunakea Spectroscopic Explore

Mycotoxin Exposure and Renal Cell Carcinoma Risk: An Association Study in the EPIC European Cohort

Background: Mycotoxins have been suggested to contribute to a spectrum of adverse health effects in humans, including at low concentrations. The recognition of these food contaminants being carcinogenic, as co-occurring rather than as singularly present, has emerged from recent research. The aim of this study was to assess the potential associations of single and multiple mycotoxin exposures with renal cell carcinoma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: Food questionnaire data from the EPIC cohort were matched to mycotoxin food occurrence data compiled by the European Food Safety Authority (EFSA) from European Member States to assess long-term dietary mycotoxin exposures, and to associate these with the risk of renal cell carcinoma (RCC, n = 911 cases) in 450,112 EPIC participants. Potential confounding factors were taken into account. Analyses were conducted using Cox's proportional hazards regression models to compute hazard ratios (HRs) and 95% confidence intervals (95% CIs) with mycotoxin exposures expressed as mu g/kg body weight/day. Results: Demographic characteristics differed between the RCC cases and non-cases for body mass index, age, alcohol intake at recruitment, and other dietary factors. In addition, the mycotoxin exposure distributions showed that a large proportion of the EPIC population was exposed to some of the main mycotoxins present in European foods such as deoxynivalenol (DON) and derivatives, fumonisins, Fusarium toxins, Alternaria toxins, and total mycotoxins. Nevertheless, no statistically significant associations were observed between the studied mycotoxins and mycotoxin groups, and the risk of RCC development. Conclusions: These results show an absence of statistically significant associations between long-term dietary mycotoxin exposures and RCC risk. However, these results need to be validated in other cohorts and preferably using repeated dietary exposure measurements. In addition, more occurrence data of, e.g., citrinin and fumonisins in different food commodities and countries in the EFSA database are a prerequisite to establish a greater degree of certainty