A Cost-Effectiveness Protocol for Flood-Mitigation Plans Based on Leeds’ Boxing Day 2015 Floods

Inspired by the Boxing Day 2015 flood of the River Aire in Leeds, UK, and subsequent attempts to mitigate adverse consequences of flooding, the goals considered are: (i) to revisit the concept of flood-excess volume (FEV) as a complementary diagnostic for classifying flood events; (ii) to establish a new roadmap/protocol for assessing flood-mitigation schemes using FEV; and, (iii) to provide a clear, graphical cost-effectiveness analysis of flood mitigation, exemplified for a hypothetical scheme partially based on actual plans. We revisit the FEV concept and present it as a three-panel graph using thresholds and errors. By re-expressing FEV as a 2m -deep square lake of equivalent capacity, one can visualise its dimensions in comparison with the river valley considered. Cost-effectiveness of flood-mitigation measures is expressed within the FEV square-lake; different scenarios of our hypothetical flood-mitigation scheme are then presented and assessed graphically, with each scenario involving a combination, near and further upstream of Leeds, of higher (than existing) flood-defence walls, enhanced flood-plain storage sites, giving-room-to-the-river bed-widening and natural flood management. Our cost-effectiveness analysis is intended as a protocol to compare and choose between flood-mitigation scenarios in a quantifiable and visual manner, thereby offering better prospects of being understood by a wide audience, including citizens and city-council planners. Using techniques of data analysis combined with general river hydraulics, common-sense and upper-bound estimation, we offer an accessible check of flood-mitigation plans

Genomic and transcriptomic analysis of the streptomycin-dependent Mycobacterium tuberculosis strain 18b.

The ability of Mycobacterium tuberculosis to establish a latent infection (LTBI) in humans confounds the treatment of tuberculosis. Consequently, there is a need to discover new therapeutic agents that can kill M. tuberculosis both during active disease and LTBI. The streptomycin-dependent strain of M. tuberculosis, 18b, provides a useful tool for this purpose since upon removal of streptomycin (STR) it enters a non-replicating state that mimics latency both in vitro and in animal models. The 4.41 Mb genome sequence of M. tuberculosis 18b was determined and this revealed the strain to belong to clade 3 of the ancient ancestral lineage of the Beijing family. STR-dependence was attributable to insertion of a single cytosine in the 530 loop of the 16S rRNA and to a single amino acid insertion in the N-terminal domain of initiation factor 3. RNA-seq was used to understand the genetic programme activated upon STR-withdrawal and hence to gain insight into LTBI. This revealed reconfiguration of gene expression and metabolic pathways showing strong similarities between non-replicating 18b and M. tuberculosis residing within macrophages, and with the core stationary phase and microaerophilic responses. The findings of this investigation confirm the validity of 18b as a model for LTBI, and provide insight into both the evolution of tubercle bacilli and the functioning of the ribosome

Rare De Novo Missense Variants in RNA Helicase DDX6 Cause Intellectual Disability and Dysmorphic Features and Lead to P-Body Defects and RNA Dysregulation

Item does not contain fulltex

Investigation of optical and electrical properties of erbium-doped TiO2 thin films for photodetector applications

We have investigated the electrical and optical properties of erbium (Er3+) doped TiO2 thin films (Er:TiO2 TFs) grown by sol–gel technique on glass and silicon substrates. The samples were characterized by field emission gun–scanning electron microscopes (FEG–SEM), energy dispersive X-ray spectroscopy (EDX), atomic force microscopy (AFM), X-ray diffraction (XRD), photoluminescence (PL) and current–voltage measurement techniques. FEG–SEM and AFM images showed the morphological change in the structure of Er:TiO2 TFs and EDX analysis confirmed the Er3+ doped into TiO2 lattice. Broad PL emissions in visible and infrared regions were observed in undoped TiO2 samples and associated to different mechanisms due to the anatase and rutile phases. PL spectra revealed sharp peaks at 525 nm, 565 nm, 667 nm and 1.54 µm which are related to Er3+ emissions in Er:TiO2 samples. The undoped TiO2 and Er:TiO2 TFs based UV-photodetectors were fabricated, and various device parameters were investigated. The doped devices exhibit high photoresponse upon illuminating 350 nm UV light at 2 V bias with faster response time compared to undoped device

A population genetic approach to mapping neurological disorder genes using deep resequencing

Deep resequencing of functional regions in human genomes is key to identifying potentially causal rare variants for complex disorders. Here, we present the results from a large-sample resequencing (n  =  285 patients) study of candidate genes coupled with population genetics and statistical methods to identify rare variants associated with Autism Spectrum Disorder and Schizophrenia. Three genes, MAP1A, GRIN2B, and CACNA1F, were consistently identified by different methods as having significant excess of rare missense mutations in either one or both disease cohorts. In a broader context, we also found that the overall site frequency spectrum of variation in these cases is best explained by population models of both selection and complex demography rather than neutral models or models accounting for complex demography alone. Mutations in the three disease-associated genes explained much of the difference in the overall site frequency spectrum among the cases versus controls. This study demonstrates that genes associated with complex disorders can be mapped using resequencing and analytical methods with sample sizes far smaller than those required by genome-wide association studies. Additionally, our findings support the hypothesis that rare mutations account for a proportion of the phenotypic variance of these complex disorders

Compared to conventional, ecological intensive management promotes beneficial proteolytic soil microbial communities for agro-ecosystem functioning under climate change-induced rain regimes

Projected climate change and rainfall variability will affect soil microbial communities, biogeochemical cycling and agriculture. Nitrogen (N) is the most limiting nutrient in agroecosystems and its cycling and availability is highly dependent on microbial driven processes. In agroecosystems, hydrolysis of organic nitrogen (N) is an important step in controlling soil N availability. We analyzed the effect of management (ecological intensive vs. conventional intensive) on N-cycling processes and involved microbial communities under climate change-induced rain regimes. Terrestrial model ecosystems originating from agroecosystems across Europe were subjected to four different rain regimes for 263 days. Using structural equation modelling we identified direct impacts of rain regimes on N-cycling processes, whereas N-related microbial communities were more resistant. In addition to rain regimes, management indirectly affected N-cycling processes via modifications of N-related microbial community composition. Ecological intensive management promoted a beneficial N-related microbial community composition involved in N-cycling processes under climate change-induced rain regimes. Exploratory analyses identified phosphorus-associated litter properties as possible drivers for the observed management effects on N-related microbial community composition. This work provides novel insights into mechanisms controlling agro-ecosystem functioning under climate change

Produção animal na Região Metropolitana de Campinas.

bitstream/item/201050/1/5016.pd

Focal non granulomatous orchitis in a patient with Crohn’s disease

Crohn’s disease is a systemic disease and sometimes involves the testicle, usually leading to granulomatous lesions. We report herein a case of focal non-granulomatous orchitis in a 21-year-old patient with active Crohn’s disease treated by an anti-tumor necrosis factor monoclonal antibody. This circumscribed testicular lesion mimicked a tumor, leading to orchiectomy. Pre-operative blood tests (i.e. alpha-fetoprotein, lactate dehydrogenase and human chorionic gonadotrophin) were strictly normal Pathological examination of the testicle revealed a focal inflammatory infiltrate predominantly composed of lymphocytes accompanied by few plasma cells, lacking giant cells or granulomas. Importantly, intratubular germ cell neoplasia, atrophy or lithiasis were not observed. After discussing and excluding other plausible causes (burnt-out /regressed germ cell tumor, infection, vascular or traumatic lesions, iatrogenic effects), we concluded that this particular case of orchitis was most likely an extra-digestive manifestation of inflammatory bowel disease. To our knowledge, this is the first described case of focal non-granulomatous orchitis associated with Crohn’s disease. Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/211774728416011

Identification of ChIP-seq mapped targets of HP1β due to bombesin/GRP receptor activation

Epithelial cells lining the adult colon do not normally express gastrin-releasing peptide (GRP) or its receptor (GRPR). In contrast, GRP/GRPR can be aberrantly expressed in human colorectal cancer (CRC) including Caco-2 cells. We have previously shown that GRPR activation results in the up-regulation of HP1β, an epigenetic modifier of gene transcription. The aim of this study was to identify the genes whose expression is altered by HP1β subsequent to GRPR activation. We determined HP1β binding positions throughout the genome using chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq). After exposure to GRP, we identified 9,625 genomic positions occupied by HP1β. We performed gene microarray analysis on Caco-2 cells in the absence and presence of a GRPR specific antagonist as well as siRNA to HP1β. The expression of 97 genes was altered subsequent to GRPR antagonism, while the expression of 473 genes was altered by HP1β siRNA exposure. When these data were evaluated in concert with our ChIP-seq findings, 9 genes showed evidence of possible altered expression as a function of GRPR signaling via HP1β. Of these, genomic PCR of immunoprecipitated chromatin demonstrated that GRPR signaling affected the expression of IL1RAPL2, FAM13A, GBE1, PLK3, and SLCO1B3. These findings provide the first evidence by which GRPR aberrantly expressed in CRC might affect tumor progression