Visible-Light-Activated Molecular Nanomachines Kill Pancreatic Cancer Cells

Recently, synthetic molecular nanomachines (MNMs) that rotate unidirectionally in response to UV light excitation have been used to produce nanomechanical action on live cells to kill them through the drilling of holes in their cell membranes. In the work here, visible-light-absorbing MNMs are designed and synthesized to enable nanomechanical activation by 405 nm light, thereby using a wavelength of light that is less phototoxic than the previously employed UV wavelengths. Visible-light-absorbing MNMs that kill pancreatic cancer cells upon response to light activation are demonstrated. Evidence is presented to support the conclusion that MNMs do not kill cancer cells by the photothermal effect when used at low optical density. In addition, MNMs suppress the formation of reactive oxygen species, leaving nanomechanical action as the most plausible working mechanism for cell killing under the experimental conditions

First passage and arrival time densities for L\'evy flights and the failure of the method of images

We discuss the first passage time problem in the semi-infinite interval, for homogeneous stochastic Markov processes with L{\'e}vy stable jump length distributions $\lambda(x)\sim\ell^{\alpha}/|x|^{1+\alpha}$ ($|x|\gg\ell$), namely, L{\'e}vy flights (LFs). In particular, we demonstrate that the method of images leads to a result, which violates a theorem due to Sparre Andersen, according to which an arbitrary continuous and symmetric jump length distribution produces a first passage time density (FPTD) governed by the universal long-time decay $\sim t^{-3/2}$. Conversely, we show that for LFs the direct definition known from Gaussian processes in fact defines the probability density of first arrival, which for LFs differs from the FPTD. Our findings are corroborated by numerical results.Comment: 8 pages, 3 figures, iopart.cls style, accepted to J. Phys. A (Lett

Adaptive Lévy processes and area-restricted search in human foraging

A considerable amount of research has claimed that animals’ foraging behaviors display movement lengths with power-law distributed tails, characteristic of Lévy flights and Lévy walks. Though these claims have recently come into question, the proposal that many animals forage using Lévy processes nonetheless remains. A Lévy process does not consider when or where resources are encountered, and samples movement lengths independently of past experience. However, Lévy processes too have come into question based on the observation that in patchy resource environments resource-sensitive foraging strategies, like area-restricted search, perform better than Lévy flights yet can still generate heavy-tailed distributions of movement lengths. To investigate these questions further, we tracked humans as they searched for hidden resources in an open-field virtual environment, with either patchy or dispersed resource distributions. Supporting previous research, for both conditions logarithmic binning methods were consistent with Lévy flights and rank-frequency methods–comparing alternative distributions using maximum likelihood methods–showed the strongest support for bounded power-law distributions (truncated Lévy flights). However, goodness-of-fit tests found that even bounded power-law distributions only accurately characterized movement behavior for 4 (out of 32) participants. Moreover, paths in the patchy environment (but not the dispersed environment) showed a transition to intensive search following resource encounters, characteristic of area-restricted search. Transferring paths between environments revealed that paths generated in the patchy environment were adapted to that environment. Our results suggest that though power-law distributions do not accurately reflect human search, Lévy processes may still describe movement in dispersed environments, but not in patchy environments–where search was area-restricted. Furthermore, our results indicate that search strategies cannot be inferred without knowing how organisms respond to resources–as both patched and dispersed conditions led to similar Lévy-like movement distributions

Changes in the socio-ecological system of a protected area in the yucatan peninsula: A case study on land-use, vegetation cover, and household management strategies

Protected areas (PA) are effective means for protecting biodiversity, but less is known about their effect on the social-ecological system (SES). Using a semi-experimental approach and a descriptive case study based evaluation, we analyzed the effect of a PA in the Yucatan Peninsula on land-cover and household resource management strategies in time and space (before and after the PA establishment; inside and outside its limits). To assess the changes of land-use practices in the areas surrounding the communities inside and outside the PA, and their change over time (from 2003 to 2015), we used remote sensing analysis and semi-structured interviews. Our results show that after the PA was established, the forest increased and agricultural plots decreased inside and to a lesser extent outside the PA. However, fires reduced the area of old-growth forest and increased young secondary forest, highlighting the system’s vulnerability to uncommon events. Resource management strategies were also affected: while inside the PA households tended toward specializing on tourism, outside the PA household strategies implied a diversification of productive activities. Overall, the establishment of the PA proved to be an effective tool to promote forest recovery and prevent deforestation in the regions surrounding the communities both inside and outside the PA

Indium-decorated Pd nanocubes degrade nitrate anions rapidly

Indium-decorated palladium nanoparticles (In-on-PdNPs) are active for room-temperature catalytic reduction of aqueous nitrate, where the active sites are metallic In atoms on the Pd surface. The PdNPs are pseudo-spherical in shape, and it is unclear if their faceted nature plays a role in nitrate reduction. We synthesized different-sized, cube-shaped NPs with differing In coverages (sc%), and studied the resultant In-on-Pd-nanocubes (NCs) for nitrate reduction. The NCs exhibited volcano-shape activity dependence on In sc%, with peak activity around 65–75 sc%. When rate constants were normalized to undercoordinated atoms (at edge + corners), the NCs exhibited near-identical maximum activity (20×-higher than In-on-PdNPs) at ρIn/Pd edge+corner ∼0.5 (∼5 In atoms per 10 edge and corner atoms). NCs with a higher In edge + corner density (ρIn/Pd edge+corner ∼1.5) were less active but did not generate NH4+ at nitrate conversions tested up to 36 %. Edge-decorated cubes may be the structural basis of improved bimetallic catalytic denitrification of water

Evolution of form in metal-organic frameworks

Self-assembly has proven to be a widely successful synthetic strategy for functional materials, especially for metal-organic materials (MOMs), an emerging class of porous materials consisting of metal-organic frameworks (MOFs) and metal-organic polyhedra (MOPs). However, there are areas in MOM synthesis in which such self-assembly has not been fully utilized, such as controlling the interior of MOM crystals. Here we demonstrate sequential self-assembly strategy for synthesizing various forms of MOM crystals, including double-shell hollow MOMs, based on single-crystal to single-crystal transformation from MOP to MOF. Moreover, this synthetic strategy also yields other forms, such as solid, core-shell, double and triple matryoshka, and single-shell hollow MOMs, thereby exhibiting form evolution in MOMs. We anticipate that this synthetic approach might open up a new direction for the development of diverse forms in MOMs, with highly advanced areas such as sequential drug delivery/release and heterogeneous cascade catalysis targeted in the foreseeable future.ope

Towards precision medicine: defining and characterizing adipose tissue dysfunction to identify early immunometabolic risk in symptom-free adults from the GEMM family study

Interactions between macrophages and adipocytes are early molecular factors influencing adipose tissue (AT) dysfunction, resulting in high leptin, low adiponectin circulating levels and low-grade metaflammation, leading to insulin resistance (IR) with increased cardiovascular risk. We report the characterization of AT dysfunction through measurements of the adiponectin/leptin ratio (ALR), the adipo-insulin resistance index (Adipo-IRi), fasting/postprandial (F/P) immunometabolic phenotyping and direct F/P differential gene expression in AT biopsies obtained from symptom-free adults from the GEMM family study. AT dysfunction was evaluated through associations of the ALR with F/P insulin-glucose axis, lipid-lipoprotein metabolism, and inflammatory markers. A relevant pattern of negative associations between decreased ALR and markers of systemic low-grade metaflammation, HOMA, and postprandial cardiovascular risk hyperinsulinemic, triglyceride and GLP-1 curves was found. We also analysed their plasma non-coding microRNAs and shotgun lipidomics profiles finding trends that may reflect a pattern of adipose tissue dysfunction in the fed and fasted state. Direct gene differential expression data showed initial patterns of AT molecular signatures of key immunometabolic genes involved in AT expansion, angiogenic remodelling and immune cell migration. These data reinforce the central, early role of AT dysfunction at the molecular and systemic level in the pathogenesis of IR and immunometabolic disorders

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015

Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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