Impact of low intensity summer rainfall on E. coli-discharge event dynamics with reference to sample acquisition and storage

Understanding the role of different rainfall scenarios on faecal indicator organism (FIO) dynamics under variable field conditions is important to strengthen the evidence base on which regulators and land managers can base informed decisions regarding diffuse microbial pollution risks. We sought to investigate the impact of low intensity summer rainfall on Escherichia coli-discharge (Q) patterns at the headwater catchment scale in order to provide new empirical data on FIO concentrations observed during baseflow conditions. In addition, we evaluated the potential impact of using automatic samplers to collect and store freshwater samples for subsequent microbial analysis during summer storm sampling campaigns. The temporal variation of E. coli concentrations with Q was captured during six events throughout a relatively dry summer in central Scotland. The relationship between E. coli concentration and Q was complex with no discernible patterns of cell emergence with Q that were repeated across all events. On several occasions, an order of magnitude increase in E. coli concentrations occurred even with slight increases in Q, but responses were not consistent and highlighted the challenges of attempting to characterise temporal responses of E. coli concentrations relative to Q during low intensity rainfall. Cross-comparison of E. coli concentrations determined in water samples using simultaneous manual grab and automated sample collection was undertaken with no difference in concentrations observed between methods. However, the duration of sample storage within the autosampler unit was found to be more problematic in terms of impacting on the representativeness of microbial water quality, with unrefrigerated autosamplers exhibiting significantly different concentrations of E. coli relative to initial samples after 12-h storage. The findings from this study provide important empirical contributions to the growing evidence base in the field of catchment microbial dynamics

Concrete box-units for housing.

Thesis. 1975. M.Arch.A.S.--Massachusetts Institute of Technology. Dept. of Architecture.Includes bibliographical references.M.Arch.A.S

How to save the world with Leerdammer cheese:Engineering nanoporous materials for clean water

Water is the single most important substance on Earth, it is vital for all known forms of life. Water scarcity however, means that one in five people on this planet lack access to clean, safe drinking water. Water scarcity is not just caused by an uneven distribution of water resources, but also a severe decrease in water quality. Declining water quality has been recognised by the United Nations as a rapidly emerging issue, one that will have a large impact on both developing and developed countries, including the United Kingdom. The decline in water quality is due to an increase in the number of chemicals, including pharmaceuticals and pesticides, entering the water supply. Research is now focusing on cheaper and more efficient methods to remove these contaminants.One potential solution is to use a class of materials which have a lot in common with Leerdammer cheese. These so-called nanoporous materials are not usually bright yellow, and neither are they really edible. They are however full of thousands of nano-scale sized holes or pores (a nanometre is one millionth of a millimetre), and it is this property which makes them potentially world-saving. Molecules are able to stick to the surface of nanoporous materials, by a process known as adsorption. On passing untreated water through this type of material, undesirable molecules can be stored on the materials surface, and removed from the water supply. One type of nanoporous material is known as activated carbon, and it is already used in water treatment. These materials are one of the oldest known and most efficient water treatment methods. Despite this, current activated carbon materials are unable to completely remove all contaminants from the water supply. Only a limited amount of certain contaminants, such as the pesticide metaldehyde, are removed using current activated carbon materials. Our research focuses on the development of novel activated carbon materials, which will be able to remove these challenging contaminants from the water supply. The performance of nanoporous materials is affected by several factors. We are investigating the optimal pore size and shape for our Leerdammer cheese-like materials. Our research focuses on upgrading a waste product, called lignin, into an activated carbon. Lignin is a component in biomass, and is produced in large quantities by the paper pulping industry. The wide-spread availability and low cost of lignin makes this a promising feedstock for industrial-scale production of novel activated carbons. Uniquely the structure of lignin depends on the type of plant it is extracted from. This leads to the exciting possibility we will be able to tune the activated carbon structure, including the size and shape of its pores, simply by adjusting the feedstock. Further, this could enable us to selectively remove some of the more challenging contaminants from the water supply, by producing this type of tailored activated carbon. Severely declining water quality is fast becoming an urgent problem. Our research is working towards the producing more efficient Leerdammer cheese-like materials to help save the world.<br/

A HIF-LIMD1 negative feedback mechanism mitigates the pro-tumorigenic effects of hypoxia

The adaptive cellular response to low oxygen tensions is mediated by the hypoxia inducible factors (HIFs), a family of heterodimeric transcription factors composed of HIF-α and β subunits. Prolonged HIF expression is a key contributor to cellular transformation, tumourigenesis and metastasis. As such, HIF degradation under hypoxic conditions is an essential homeostatic and tumour suppressive mechanism. LIMD1 complexes with PHD2 and VHL in physiological oxygen levels (normoxia) to facilitate proteasomal degradation of the HIF-α subunit. Here, we identify LIMD1 as a HIF-1 target gene, which mediates a previously uncharacterised, negative regulatory feedback mechanism for hypoxic HIF-α degradation by modulating PHD2-LIMD1- VHL complex formation. Hypoxic induction of LIMD1 expression results in increased HIF-α protein degradation, inhibiting HIF-1 target-gene expression, tumour growth and vascularisation. Furthermore, we report that copy number variation at the LIMD1 locus occurs in 47.1% of lung adenocarcinoma patients, correlates with enhanced expression of a HIF target gene signature and is a negative prognostic indicator. Taken together, our data open a new field of research into the aetiology, diagnosis and prognosis of LIMD1-negative lung cancers

The PARP inhibitor AZD2461 provides insights into the role of PARP3 inhibition for both synthetic lethality and tolerability with chemotherapy in preclinical models

The PARP inhibitor AZD2461 was developed as a next-generation agent following olaparib, the first PARP inhibitor approved for cancer therapy. In BRCA1-deficient mouse models, olaparib resistance predominantly involves overexpression of P-glycoprotein,so AZD2461 was developed as a poor substrate for drug transporters. Here we demonstrate the efficacy of this compound against olaparib-resistant tumors that overexpress P-glycoprotein. In addition, AZD2461 was better tolerated in combination with chemotherapy than olaparib in mice, which suggests that AZD2461 could have significant advantages over olaparib in the clinic. However, this superior toxicity profile did not extend to rats. Investigations of this difference revealed a differential PARP3 inhibitory activity for each compound and a higher level of PARP3 expression in bone marrow cells from mice as compared with rats and humans. Our findings have implications for the use of mouse models to assess bone marrow toxicity for DNA-damaging agents and inhibitors of the DNA damage response. Finally, structural modeling of the PARP3-active site with different PARP inhibitors also highlights the potential to develop compounds with different PARP family member specificity profiles for optimal antitumor activity and tolerability

How to save the world with Leerdammer cheese:Engineering nanoporous materials for clean water

Water is the single most important substance on Earth, it is vital for all known forms of life. Water scarcity however, means that one in five people on this planet lack access to clean, safe drinking water. Water scarcity is not just caused by an uneven distribution of water resources, but also a severe decrease in water quality. Declining water quality has been recognised by the United Nations as a rapidly emerging issue, one that will have a large impact on both developing and developed countries, including the United Kingdom. The decline in water quality is due to an increase in the number of chemicals, including pharmaceuticals and pesticides, entering the water supply. Research is now focusing on cheaper and more efficient methods to remove these contaminants.One potential solution is to use a class of materials which have a lot in common with Leerdammer cheese. These so-called nanoporous materials are not usually bright yellow, and neither are they really edible. They are however full of thousands of nano-scale sized holes or pores (a nanometre is one millionth of a millimetre), and it is this property which makes them potentially world-saving. Molecules are able to stick to the surface of nanoporous materials, by a process known as adsorption. On passing untreated water through this type of material, undesirable molecules can be stored on the materials surface, and removed from the water supply. One type of nanoporous material is known as activated carbon, and it is already used in water treatment. These materials are one of the oldest known and most efficient water treatment methods. Despite this, current activated carbon materials are unable to completely remove all contaminants from the water supply. Only a limited amount of certain contaminants, such as the pesticide metaldehyde, are removed using current activated carbon materials. Our research focuses on the development of novel activated carbon materials, which will be able to remove these challenging contaminants from the water supply. The performance of nanoporous materials is affected by several factors. We are investigating the optimal pore size and shape for our Leerdammer cheese-like materials. Our research focuses on upgrading a waste product, called lignin, into an activated carbon. Lignin is a component in biomass, and is produced in large quantities by the paper pulping industry. The wide-spread availability and low cost of lignin makes this a promising feedstock for industrial-scale production of novel activated carbons. Uniquely the structure of lignin depends on the type of plant it is extracted from. This leads to the exciting possibility we will be able to tune the activated carbon structure, including the size and shape of its pores, simply by adjusting the feedstock. Further, this could enable us to selectively remove some of the more challenging contaminants from the water supply, by producing this type of tailored activated carbon. Severely declining water quality is fast becoming an urgent problem. Our research is working towards the producing more efficient Leerdammer cheese-like materials to help save the world.<br/

Genome-wide association study of germline variants and breast cancer-specific mortality.

BackgroundWe examined the associations between germline variants and breast cancer mortality using a large meta-analysis of women of European ancestry.MethodsMeta-analyses included summary estimates based on Cox models of twelve datasets using ~10.4 million variants for 96,661 women with breast cancer and 7697 events (breast cancer-specific deaths). Oestrogen receptor (ER)-specific analyses were based on 64,171 ER-positive (4116) and 16,172 ER-negative (2125) patients. We evaluated the probability of a signal to be a true positive using the Bayesian false discovery probability (BFDP).ResultsWe did not find any variant associated with breast cancer-specific mortality at P &lt; 5 × 10-8. For ER-positive disease, the most significantly associated variant was chr7:rs4717568 (BFDP = 7%, P = 1.28 × 10-7, hazard ratio [HR] = 0.88, 95% confidence interval [CI] = 0.84-0.92); the closest gene is AUTS2. For ER-negative disease, the most significant variant was chr7:rs67918676 (BFDP = 11%, P = 1.38 × 10-7, HR = 1.27, 95% CI = 1.16-1.39); located within a long intergenic non-coding RNA gene (AC004009.3), close to the HOXA gene cluster.ConclusionsWe uncovered germline variants on chromosome 7 at BFDP &lt; 15% close to genes for which there is biological evidence related to breast cancer outcome. However, the paucity of variants associated with mortality at genome-wide significance underpins the challenge in providing genetic-based individualised prognostic information for breast cancer patients

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Measurements of the pp → ZZ production cross section and the Z → 4ℓ branching fraction, and constraints on anomalous triple gauge couplings at √s = 13 TeV

Four-lepton production in proton-proton collisions, pp -> (Z/gamma*)(Z/gamma*) -> 4l, where l = e or mu, is studied at a center-of-mass energy of 13 TeV with the CMS detector at the LHC. The data sample corresponds to an integrated luminosity of 35.9 fb(-1). The ZZ production cross section, sigma(pp -> ZZ) = 17.2 +/- 0.5 (stat) +/- 0.7 (syst) +/- 0.4 (theo) +/- 0.4 (lumi) pb, measured using events with two opposite-sign, same-flavor lepton pairs produced in the mass region 60 4l) = 4.83(-0.22)(+0.23) (stat)(-0.29)(+0.32) (syst) +/- 0.08 (theo) +/- 0.12(lumi) x 10(-6) for events with a four-lepton invariant mass in the range 80 4GeV for all opposite-sign, same-flavor lepton pairs. The results agree with standard model predictions. The invariant mass distribution of the four-lepton system is used to set limits on anomalous ZZZ and ZZ. couplings at 95% confidence level: -0.0012 < f(4)(Z) < 0.0010, -0.0010 < f(5)(Z) < 0.0013, -0.0012 < f(4)(gamma) < 0.0013, -0.0012 < f(5)(gamma) < 0.0013

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis