Enzyme treatment to decrease solids and improve digestion of primary sewage sludge

The aim of anaerobic digestion of primary sewage sludge is to convert the carbonaceous material contained in the solids into methane and carbon dioxide. The products of digestion are therefore gases, stabilised sludge solids which are subsequently dewatered and disposed of, and sludge liquor which is generally further treated. This investigation assessed the impact of addition of hydrolytic enzymes to anaerobic digesters. Cellulase and pronase E were added singly and in combination, and it was foundthat the mixture of the two enzymes resulted in an 80% reduction in solids (cf. 20% in the control), 93% removal of particulate chemical oxygen demand (COD) (59% in the control) and 97% total COD removal(vs. 63%). The total suspended solids (TSS) concentration was reduced by 80%, from 25 g/l to 5 g/l. Single enzymes had little or no impact on sludge solubilisation, and final COD and TSS, but all of the enzyme additions were seen to decrease the production of volatile fatty acids (VFAs). Since accumulation of VFAs can lead to digester failure, it was concluded that the enzyme additives enhanced digester performance in terms of degradation of COD, reduction in sludge solids remaining afterdigestion and improved digester stability owing to the stable prevailing pH. The results indicate that enzyme addition at full scale could be expected to lead to greater methane yields, lower strength sludge liquors and a significant reduction in the requirements for and costs of digested sludge dewatering and disposa

Quantum-Dense Metrology

Quantum metrology utilizes entanglement for improving the sensitivity of measurements. Up to now the focus has been on the measurement of just one out of two non-commuting observables. Here we demonstrate a laser interferometer that provides information about two non-commuting observables, with uncertainties below that of the meter's quantum ground state. Our experiment is a proof-of-principle of quantum dense metrology, and uses the additional information to distinguish between the actual phase signal and a parasitic signal due to scattered and frequency shifted photons. Our approach can be readily applied to improve squeezed-light enhanced gravitational-wave detectors at non-quantum noise limited detection frequencies in terms of a sub shot-noise veto-channel.Comment: 5 pages, 3 figures; includes supplementary material

A Screen for Genes Expressed in the Olfactory Organs of Drosophila melanogaster Identifies Genes Involved in Olfactory Behaviour

BACKGROUND: For insects the sense of smell and associated olfactory-driven behaviours are essential for survival. Insects detect odorants with families of olfactory receptor proteins that are very different to those of mammals, and there are likely to be other unique genes and genetic pathways involved in the function and development of the insect olfactory system. METHODOLOGY/PRINCIPAL FINDINGS: We have performed a genetic screen of a set of 505 Drosophila melanogaster gene trap insertion lines to identify novel genes expressed in the adult olfactory organs. We identified 16 lines with expression in the olfactory organs, many of which exhibited expression of the trapped genes in olfactory receptor neurons. Phenotypic analysis showed that six of the lines have decreased olfactory responses in a behavioural assay, and for one of these we showed that precise excision of the P element reverts the phenotype to wild type, confirming a role for the trapped gene in olfaction. To confirm the identity of the genes trapped in the lines we performed molecular analysis of some of the insertion sites. While for many lines the reported insertion sites were correct, we also demonstrated that for a number of lines the reported location of the element was incorrect, and in three lines there were in fact two pGT element insertions. CONCLUSIONS/SIGNIFICANCE: We identified 16 new genes expressed in the Drosophila olfactory organs, the majority in neurons, and for several of the gene trap lines demonstrated a defect in olfactory-driven behaviour. Further characterisation of these genes and their roles in olfactory system function and development will increase our understanding of how the insect olfactory system has evolved to perform the same essential function to that of mammals, but using very different molecular genetic mechanisms

Diagnostic accuracy of consensus diagnostic criteria for frontotemporal dementia in a memory clinic population

Background/Aims: The goal of the present study was to evaluate the diagnostic accuracy of the core diagnostic criteria for frontotemporal dementia (FTD) [Neary D, et al: Neurology 1998;51:1546-1554] within a memory clinic population. Methods: The 5 core diagnostic criteria for FTD were operationalised in an informant-based written questionnaire. For a diagnosis of FTD the total clinical picture was weighted with findings on additional investigations and possible exclusion criteria, with follow-up of at least 1 year. Results: The operationalised core criteria for FTD had a sensitivity of 79% (95% CI = 57-92) and a specificity of 90% (95% CI = 85-94). Conclusion: The core diagnostic criteria for FTD applied in a caregiver questionnaire have good diagnostic accuracy among subjects without advanced dementia attending a memory clinic. This stresses the importance of the informant-based history in the differential diagnosis of dementia. Copyrigh

Small but crucial : the novel small heat shock protein Hsp21 mediates stress adaptation and virulence in Candida albicans

Peer reviewedPublisher PD

The Origins of Concentric Demyelination: Self-Organization in the Human Brain

Baló's concentric sclerosis is a rare atypical form of multiple sclerosis characterized by striking concentric demyelination patterns. We propose a robust mathematical model for Baló's sclerosis, sharing common molecular and cellular mechanisms with multiple sclerosis. A reconsideration of the analogies between Baló's sclerosis and the Liesegang periodic precipitation phenomenon led us to propose a chemotactic cellular model for this disease. Rings of demyelination appear as a result of self-organization processes, and closely mimic Baló lesions. According to our results, homogeneous and concentric demyelinations may be two different macroscopic outcomes of a single fundamental immune disorder. Furthermore, in chemotactic models, cellular aggressivity appears to play a central role in pattern formation

A Novel, “Double-Clamp” Binding Mode for Human Heme Oxygenase-1 Inhibition

The development of heme oxygenase (HO) inhibitors is critical in dissecting and understanding the HO system and for potential therapeutic applications. We have established a program to design and optimize HO inhibitors using structure-activity relationships in conjunction with X-ray crystallographic analyses. One of our previous complex crystal structures revealed a putative secondary hydrophobic binding pocket which could be exploited for a new design strategy by introducing a functional group that would fit into this potential site. To test this hypothesis and gain further insights into the structural basis of inhibitor binding, we have synthesized and characterized 1-(1H-imidazol-1-yl)-4,4-diphenyl-2-butanone (QC-308). Using a carbon monoxide (CO) formation assay on rat spleen microsomes, the compound was found to be ∼15 times more potent (IC50 = 0.27±0.07 µM) than its monophenyl analogue, which is already a potent compound in its own right (QC-65; IC50 = 4.0±1.8 µM). The crystal structure of hHO-1 with QC-308 revealed that the second phenyl group in the western region of the compound is indeed accommodated by a definitive secondary proximal hydrophobic pocket. Thus, the two phenyl moieties are each stabilized by distinct hydrophobic pockets. This “double-clamp” binding offers additional inhibitor stabilization and provides a new route for improvement of human heme oxygenase inhibitors

A Whole Virus Pandemic Influenza H1N1 Vaccine Is Highly Immunogenic and Protective in Active Immunization and Passive Protection Mouse Models

The recent emergence and rapid spread of a novel swine-derived H1N1 influenza virus has resulted in the first influenza pandemic of this century. Monovalent vaccines have undergone preclinical and clinical development prior to initiation of mass immunization campaigns. We have carried out a series of immunogenicity and protection studies following active immunization of mice, which indicate that a whole virus, nonadjuvanted vaccine is immunogenic at low doses and protects against live virus challenge. The immunogenicity in this model was comparable to that of a whole virus H5N1 vaccine, which had previously been demonstrated to induce high levels of seroprotection in clinical studies. The efficacy of the H1N1 pandemic vaccine in protecting against live virus challenge was also seen to be equivalent to that of the H5N1 vaccine. The protective efficacy of the H1N1 vaccine was also confirmed using a severe combined immunodeficient (SCID) mouse model. It was demonstrated that mouse and guinea pig immune sera elicited following active H1N1 vaccination resulted in 100% protection of SCID mice following passive transfer of immune sera and lethal challenge. The immune responses to a whole virus pandemic H1N1 and a split seasonal H1N1 vaccine were also compared in this study. It was demonstrated that the whole virus vaccine induced a balanced Th-1 and Th-2 response in mice, whereas the split vaccine induced mainly a Th-2 response and only minimal levels of Th-1 responses. These data supported the initiation of clinical studies with the same low doses of whole virus vaccine that had previously been demonstrated to be immunogenic in clinical studies with a whole virus H5N1 vaccine

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

SummaryBackground 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