Theranostic nanoparticles enhance the response of glioblastomas to radiation

YesDespite considerable progress with our understanding of glioblastoma multiforme (GBM) and the precise delivery of radiotherapy, the prognosis for GBM patients is still unfavorable with tumor recurrence due to radioresistance being a major concern. We recently developed a cross-linked iron oxide nanoparticle conjugated to azademethylcolchicine (CLIO-ICT) to target and eradicate a subpopulation of quiescent cells, glioblastoma initiating cells (GICs), which could be a reason for radioresistance and tumor relapse. The purpose of our study was to investigate if CLIO-ICT has an additive therapeutic effect to enhance the response of GBMs to ionizing radiation. Methods: NSG™ mice bearing human GBMs and C57BL/6J mice bearing murine GBMs received CLIO-ICT, radiation, or combination treatment. The mice underwent pre- and post-treatment magnetic resonance imaging (MRI) scans, bioluminescence imaging (BLI), and histological analysis. Tumor nanoparticle enhancement, tumor flux, microvessel density, GIC, and apoptosis markers were compared between different groups using a one-way ANOVA and two-tailed Mann-Whitney test. Additional NSG™ mice underwent survival analyses with Kaplan–Meier curves and a log rank (Mantel–Cox) test. Results: At 2 weeks post-treatment, BLI and MRI scans revealed significant reduction in tumor size for CLIO-ICT plus radiation treated tumors compared to monotherapy or vehicle-treated tumors. Combining CLIO-ICT with radiation therapy significantly decreased microvessel density, decreased GICs, increased caspase-3 expression, and prolonged the survival of GBM-bearing mice. CLIO-ICT delivery to GBM could be monitored with MRI. and was not significantly different before and after radiation. There was no significant caspase-3 expression in normal brain at therapeutic doses of CLIO-ICT administered. Conclusion: Our data shows additive anti-tumor effects of CLIO-ICT nanoparticles in combination with radiotherapy. The combination therapy proposed here could potentially be a clinically translatable strategy for treating GBMs

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

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Centrality dependence of high-pT D meson suppression in Pb-Pb collisions at 1asNN = 2.76 TeV

The nuclear modification factor, RAA, of the prompt charmed mesons D0, D+ and D 17+, and their antiparticles, was measured with the ALICE detector in Pb-Pb collisions at a centre-of-mass energy 1asNN = 2.76 TeV in two transverse momentum intervals, 5 < pT < 8GeV/c and 8 < pT < 16GeV/c, and in six collision centrality classes. The RAA shows a maximum suppression of a factor of 5\u20136 in the 10% most central collisions. The suppression and its centrality dependence are compatible within uncertainties with those of charged pions. A comparison with the RAA of non-prompt J/\u3c8 from B meson decays, measured by the CMS Collaboration, hints at a larger suppression of D mesons in the most central collisions

4종류 입자군의 통일

Flavor unification is attempted in SU(7) and SO(14). Three different models are presented for the unification of four families of quark and lepton which are assigned to the 64 dim. spinor representation of SO(14). They are real with respect to SU(3) X SU(2) X U(I ) but complex with respect to SU(3) xSU(2) X U(l) X U(l). Salient points including proton decay of Georgi-Glashoψ SU(5)' model are accomodated in our model. An experimentally important prediction is an existence of new parity conserving neutral current about Mw. SU(7)과 S0(14)을 써서 입자군의 통일을 시도하였으며, 4종류의 구성자와 경입자들을 S0(14)의 스프노 나툼에 맞추었다. 이들은 SU(3)×SU(2)×U(1)에 대해서는 실수나툼이지만, SU(3)×SU(2)×U(1)×U(1)에 대해서는 복소나툼이 된다. 양성자 붕괴를 포함한 SU(5) 이론의 장점들을 포함하고 있으며, 실험적으로 중요한 의미를 가지는 우기성 보존의 중성류를 예시하고 있다

Molecular epidemiology and its current clinical use in cancer management

10.1016/S1470-2045(10)70005-XThe Lancet Oncology114383-39

Ozonation of return activated sludge for disintegration and solubilisation with synthesized titanium oxide as catalyst

Ozonation of activated sludge in the present of titanium dioxide (TiO2) as catalyst to enhance the production of hydroxyl radical was evaluated in comparison to the sole ozonation process. In this process, the catalytic ozontion showed improvement in increasing ozone consumption and improving activated sludge disintegration and solubilisation. The reduction of total suspended solid (TSS), volatile suspended solid (VSS) and soluble chemical oxygen demand (SCOD) solubilisation was better in the catalytic ozonation system. Initial pH 7 of activated sludge was found best to disintegrate and solubilise the sludge flocs. However upon additional of sodium hydroxide (NaOH) in pH adjustment enhanced the solubilisation of organic matter from the flocs and cells, making the initial pH 9 is the best condition for activated sludge solubilisation. Yet the initial pH 7 of activated sludge supernatant was the best condition to achieve SCOD solubilisation due to sludge floc disintegration, when it had stronger correlation between TSS reduction and SCOD solubilisation (R2=0.961). Lower amount of catalyst of 100 mgTiO2/gTSS was found to disintegrate and solubilise the activated sludge better with 30.4% TSS reduction and 25.2% SCOD solubilisation efficiency, compared to 200 mgTiO2/gTSS with 21.9% and 17.1% TSS reduction and SCOD solubilisation, respectively

Ozonation of return activated sludge for disintegration and solubilisation with synthesized titanium oxide as catalyst

Ozonation of activated sludge in the present of titanium dioxide (TiO2) as catalyst to enhance the production of hydroxyl radical was evaluated in comparison to the sole ozonation process. In this process, the catalytic ozontion showed improvement in increasing ozone consumption and improving activated sludge disintegration and solubilisation. The reduction of total suspended solid (TSS), volatile suspended solid (VSS) and soluble chemical oxygen demand (SCOD) solubilisation was better in the catalytic ozonation system. Initial pH 7 of activated sludge was found best to disintegrate and solubilise the sludge flocs. However upon additional of sodium hydroxide (NaOH) in pH adjustment enhanced the solubilisation of organic matter from the flocs and cells, making the initial pH 9 is the best condition for activated sludge solubilisation. Yet the initial pH 7 of activated sludge supernatant was the best condition to achieve SCOD solubilisation due to sludge floc disintegration, when it had stronger correlation between TSS reduction and SCOD solubilisation (R2=0.961). Lower amount of catalyst of 100 mgTiO2/gTSS was found to disintegrate and solubilise the activated sludge better with 30.4% TSS reduction and 25.2% SCOD solubilisation efficiency, compared to 200 mgTiO2/gTSS with 21.9% and 17.1% TSS reduction and SCOD solubilisation, respectively

An approximate mixed integer linear programming (MILP) model for the design of water reuse/recycle networks with minimum emergy

Recent trends in process engineering have placed increased emphasis on the design of inherently clean and efficient processes. For example, a wide range of pinch analysis and mathematical programming methods have been developed for designing schemes for water reuse/recycle in industrial plants for both grassroot design and plant retrofit. In the latter case, the conventional approach is to maximize water recovery and thereby minimize fresh water demand and effluent volume. However, it is possible that with such an approach the reductions in environmental impact brought about by saving water can be offset by other impacts arising from increased use of energy and materials in the plant after retrofit. This work presents a model for minimizing the total resource consumption impact of a water reuse/recycle network. The total impact is expressed in terms of emergy - a measure of cumulative solar energy inputs into a life cycle system. A simplified model is proposed that focuses on the impact contributions of water, electrical power and material for capital goods. Two case studies illustrate the approach. Results show that the network with the lowest total impact can be found by sacrificing water recovery for savings in energy and material use. © 2007 Curtin University of Technology and John Wiley & Sons, Ltd

Singapore Genome Variation Project: A haplotype map of three Southeast Asian populations

The Singapore Genome Variation Project (SGVP) provides a publicly available resource of 1.6 million single nucleotide polymorphisms (SNPs) genotyped in 268 individuals from the Chinese, Malay, and Indian population groups in Southeast Asia. This online database catalogs information and summaries on genotype and phased haplotype data, including allele frequencies, assessment of linkage disequilibrium (LD), and recombination rates in a format similar to the International HapMap Project. Here, we introduce this resource and describe the analysis of human genomic variation upon agglomerating data from the HapMap and the Human Genome Diversity Project, providing useful insights into the population structure of the three major population groups in Asia. In addition, this resource also surveyed across the genome for variation in regional patterns of LD between the HapMap and SGVP populations, and for signatures of positive natural selection using two well-established metrics: iHS and XP-EHH. The raw and processed genetic data, together with all population genetic summaries, are publicly available for download and browsing through a web browser modeled with the Generic Genome Browser