Building integration of photovoltaics (PV) has long been acknowledged as a key application for PV in developed countries. The avoided use of comparably priced alternatives such as polished or cut ...stone in commercial facades enables PV to be applied often at little or no additional cost. The use of semi-transparent PV modules within commercial atria represents an interesting application in this respect as they can be used to replace traditional shading solutions which often have a high maintenance burden. However, compared to standard double glazing, an element incorporating either mono or poly crystalline PV cells in a glass–glass construction comes at a cost premium. To justify such an application there must be significant added value in the PV solution. This paper critically appraises a semi-transparent PV atrium which links two administration buildings at the University of Southampton, enclosing the main campus reception desk. Choosing PV laminates for the atrium roof has multiple benefits for the building users and the wider University, such as electricity generation, solar shading, environmental and technology statements, enhanced comfort and prestigious office workspace. This paper compares alternative shading solutions for the atrium and discusses user perception of the building and the atrium’s impact on their personal workspace. It is shown that PV in commercial atria does not always have to be considered as a ‘luxury’ option. With appropriate consideration of added value factors its selection can be justified in terms of both cost and carbon footprint.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
This volume presents 19 original essays addressing what is widely regarded as the most serious problem confronting America today and for years to come – terrorism – from the unique perspective of ...criminology. The chapters collected here address such issues as the prevention of terrorism, the applicability of community policing and routine activities models of crime to the problem of terrorism, how to balance liberty and security, and how to think about and manage the fear of terrorism, as well as the coordination of federal and local efforts to prevent and counter terrorism. Criminologists on Terrorism and Homeland Security will be of interest to anyone concerned about violence prevention in general and terrorism in particular, policing, prosecution, adjudication, sentencing and restorative justice.
Acid-sensing Ion Channels in Malignant Gliomas Berdiev, Bakhrom K.; Xia, Jiazeng; McLean, Lee Anne ...
The Journal of biological chemistry,
04/2003, Volume:
278, Issue:
17
Journal Article
Peer reviewed
Open access
High grade glioma cells derived from patient biopsies express an amiloride-sensitive sodium conductance that has properties attributed to the human brain sodium channel family, also known as ...acid-sensing ion channels (ASICs). This amiloride-sensitive conductance was not detected in cells obtained from normal brain tissue or low grade or benign tumors. Differential gene profiling data showed that ASIC1 and ASIC2 mRNA were present in normal and low grade tumor cells. Although ASIC1 was present in all of the high grade glial cells examined, ASIC2 mRNA was detected in less than half. The main purpose of our work was to examine the molecular mechanisms that may underlie the constitutively activated sodium currents present in high grade glioma cells. Our results show that 1) gain-of-function mutations of ASIC1 were not present in a number of freshly resected and cultured high grade gliomas, 2) syntaxin 1A inhibited ASIC currents only when ASIC1 and ASIC2 were co-expressed, and 3) the inhibition of ASIC currents by syntaxin 1A had an absolute requirement for either γ- or δ-hENaC. Transfection of cultured cells originally derived from high grade gliomas (U87-MG and SK-MG1) with ASIC2 abolished basal amiloride-sensitive sodium conductance; this inhibition was reversed by dialysis of the cell interior with Munc-18, a syntaxin-binding protein that typically blocks the interaction of syntaxin with other proteins. Thus, syntaxin 1A cannot inhibit Na+ permeability in the absence of adequate plasma membrane ASIC2 expression, accounting for the observed functional expression of amiloride-sensitive currents in high grade glioma cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The majority of breast cancer patients is treated with breast-conserving surgery (BCS) combined with adjuvant radiation therapy. Up to 40% of patients has a tumor-positive resection margin after BCS, ...which necessitates re-resection or additional boost radiation. Cathepsin-targeted near-infrared fluorescence imaging during BCS could be used to detect residual cancer in the surgical cavity and guide additional resection, thereby preventing tumor-positive resection margins and associated mutilating treatments. The cysteine cathepsins are a family of proteases that play a major role in normal cellular physiology and neoplastic transformation. In breast cancer, the increased enzymatic activity and aberrant localization of many of the cysteine cathepsins drive tumor progression, proliferation, invasion, and metastasis. The upregulation of cysteine cathepsins in breast cancer cells indicates their potential as a target for intraoperative fluorescence imaging. This review provides a summary of the current knowledge on the role and expression of the most important cysteine cathepsins in breast cancer to better understand their potential as a target for fluorescence-guided surgery (FGS). In addition, it gives an overview of the cathepsin-targeted fluorescent probes that have been investigated preclinically and in breast cancer patients. The current review underscores that cysteine cathepsins are highly suitable molecular targets for FGS because of favorable expression and activity patterns in virtually all breast cancer subtypes. This is confirmed by cathepsin-targeted fluorescent probes that have been shown to facilitate
in vivo
breast cancer visualization and tumor resection in mouse models and breast cancer patients. These findings indicate that cathepsin-targeted FGS has potential to improve treatment outcomes in breast cancer patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
The heterozygous mutation B6;C3-Opa1Q285STOP, which models autosomal dominant optic atrophy, leads to a 50% reduction in Opa1 transcript and protein in the mouse retina and neural tissues and is ...associated with visual dysfunction and structural changes in the murine retina and optic nerve. In this article we use this model to quantify and evaluate the dendritic morphology of retinal ganglion cells. Retinal ganglion cells in Opa1+/− mutant mice (n = 16) and accompanying age- and sex-matched controls (n = 11) (age ranges of <10, 10–15 and >20 months) were labelled DiOlistically with carbocyanine dyes to quantify changes in dendritic tree architecture as a function of age. We observed localized dendritic reduction to sublamina b of the inner plexiform layer without retinal ganglion cell loss, showing dendritic pruning of on- but not off-centre retinal ganglion cells, and this effect was exacerbated with age. The mean dendritic field area was reduced in on-centre retinal ganglion cells of 10- to 15-month-old mice (−24.24%; CV = 0.68; P < 0.05) and >20-month-old mice (−43.22%; CV = 0.75; P < 0.05) compared with age-matched wild-type controls. Similar changes were seen in average total dendritic length in on-centre retinal ganglion cells of 10- to 15-month-old mice (−31.66%; CV = 0.67; P < 0.05) and >20-month-old mice (−49.55%; CV = 0.63; P < 0.05). Sholl analysis showed a marked difference in the dendritic arborization of on-centre retinal ganglion cells in the 10- to 15-month-old group (area under the curve −21.67%; P > 0.05) and of the >20-month-old group (area under the curve −42.12%; P < 0.05) compared with the control group. There was no detectable change in dendritic morphology in <10-month-old Opa1+/− mutant mice compared with wild-type (P > 0.05). No significant changes (P > 0.05) were seen in off-centre retinal ganglion cells. Finally, there was also no significant change (P > 0.05) in the retinal ganglion cell count across all age groups. In conclusion, we show dendritic pruning in on-centre retinal ganglion cells of the Opa1+/− mouse model of autosomal dominant optic atrophy from as early as 10 months of age. These results highlight the importance of normal mitochondrial fusion balance, as influenced by the OPA1 protein in maintaining the dendritic morphology of retinal ganglion cells. Dendritic pruning precedes the onset of clinical visual loss and structural changes in the optic nerve in the absence of significant cell loss.
Rural and small-scale chicken farming is a major source of income in most African countries, and chicken meat is an important source of nutrients. However, chicken meat can be contaminated with ...Campylobacter spp. and Salmonella spp., pathogens with a high reported burden of foodborne illnesses. Therefore, it is essential to control these pathogens in chicken meat. Quantitative microbial risk assessments (QMRA) can aid the development of effective food safety control measures and are currently lacking in chicken meat supply chains in the African context. In this study, we developed stochastic QMRA models for Salmonella spp. and Campylobacter spp. in the chicken meat supply chain in Burkina Faso and Ethiopia employing the modular process risk model in @Risk software. The study scope covered chicken farming, transport, slaughtering, consumer handling, and consumption. Effectiveness of candidate interventions was assessed against baseline models' outputs, which showed that the mean annual Campylobacter spp. risk estimates were 6482 cases of illness per 100,000 persons and 164 disability adjusted life years (DALYs) per 100,000 persons in Burkina Faso, and 12,145 cases and 272 DALYs per 100,000 persons in Ethiopia. For Salmonella spp., mean annual estimates were 2713 cases and 1212 DALYs per 100,000 persons in Burkina Faso, and 4745 cases and 432 DALYs per 100,000 persons in Ethiopia. Combining interventions (improved hand washing plus designated kitchen utensils plus improved cooking) resulted in 75 % risk reduction in Burkina Faso at restaurants and 93 to 94 % in Ethiopia at homes for both Salmonella spp. and Campylobacter spp. For Burkina Faso, adding good hygienic slaughter practices at the market to these combined interventions led to over 91 % microbial risk reduction. Interventions that involved multiple food safety actions in a particular step of the supply chain or combining different interventions from different steps of the supply chain resulted in more risk reduction than individual action interventions. Overall, this study demonstrates how diverse and scanty food supply chain information can be applied in QMRA to provide estimates that can be used to stimulate risk-based food safety action in African countries.
•Campylobacter, Salmonella QMRA models were developed for the chicken chain in Africa.•Multi-action interventions were more effective than single action intervention.•Campylobacter, Salmonella cases in Ethiopia were ∼ 2 times higher than in Burkina Faso.•Salmonella DALYs in Burkina Faso were ∼ 3 times higher than those in Ethiopia.•Models were most sensitive to cross contamination from utensils and hand washing in kitchens.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background The Pediatric Eosinophilic Esophagitis Symptom Score (PEESS v2.0) measures patient-relevant outcomes. However, whether patient-identified domains (dysphagia, gastroesophageal reflux ...disease GERD, nausea/vomiting, and pain) align with clinical symptomology and histopathologic and molecular features of eosinophilic esophagitis (EoE) is unclear. Objective The purpose of this study was to determine whether clinical features of EoE, measured through PEESS v2.0, associate with histopathologic and molecular features of EoE. This represents a novel approach for analysis of allergic diseases, given the availability of allergic tissue biopsy specimens. Methods We systematically recruited treated and untreated pediatric patients with EoE (aged 2-18 years) and examined parent proxy–reported symptoms using the PEESS v2.0. Clinical symptomology was collected by questionnaire. Esophageal biopsy samples were quantified for levels of eosinophils, eosinophil peroxidase (EPX) immunohistochemical staining, and mast cells. Molecular features were assessed by using the EoE Diagnostic Panel (94 EoE-related gene transcripts). Associations between domain scores and clinical symptoms and biological features were analyzed with Wilcoxon rank sum and Spearman correlation. Results The PEESS v2.0 domains correlated to specific parent-reported symptoms: dysphagia ( P = .0012), GERD ( P = .0001), and nausea/vomiting ( P < .0001). Pain correlated with multiple symptoms ( P < .0005). Dysphagia correlated most strongly with overall histopathology, particularly in the proximal esophagus ( P ≤ .0049). Markers of esophageal activity (EPX) were significantly associated with dysphagia (strongest r = 0.37, P = .02). Eosinophil levels were more associated with pain ( r = 0.27, P = .06) than dysphagia ( r = 0.24, P = .13). The dysphagia domain correlated most with esophageal gene transcript levels, predominantly with mast cell–specific genes. Conclusion We have (1) established a validated, parent proxy–reported measure for pediatric EoE, the PEESS v2.0; (2) verified that the parent proxy effectively captures symptoms; (3) determined that the dysphagia domain most closely aligns with symptoms and tissue-based molecular biomarkers; (4) established that symptoms correlate with EPX staining; and (5) observed association between mast cells and dysphagia.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
We study the static and dynamic behaviour of colloidal rods in an optical potential energy landscape. We explore the stable states of a colloidal rod in a single optical trap close to a flat wall. ...Here, two metastable states are observed, horizontal and vertical, both of which experience a parabolic potential energy landscape. Next we place a colloidal rod into a one-dimensional sinusoidal optical potential energy landscape and introduce a constant driving velocity. When driven below the critical velocity, the particle is confined to a single potential energy minimum of the optical landscape and the equilibrium position of a particle is investigated. The equilibrium position of a rod is found to vary substantially from that of a sphere, due to the drag coefficient of a rod being highly dependent on its proximity to an optical trap. The driving velocity is increased to enable the particle to traverse the periodic landscape and above the critical velocity, the average particle velocity increases as the square root of the driving velocity. When introducing oscillations to the driving velocity we observe dynamic mode locking and characterise the nature of synchronised motion of the rod-like particles.
Abstract
Differences by sex in lung cancer incidence and mortality have been reported which cannot be fully explained by sex differences in smoking behavior, implying existence of genetic and ...molecular basis for sex disparity in lung cancer development. However, the information about sex dimorphism in lung cancer risk is quite limited despite the great success in lung cancer association studies. By adopting a stringent two-stage analysis strategy, we performed a genome-wide gene–sex interaction analysis using genotypes from a lung cancer cohort including ~ 47 000 individuals with European ancestry. Three low-frequency variants (minor allele frequency < 0.05), rs17662871 odds ratio (OR) = 0.71, P = 4.29×10−8); rs79942605 (OR = 2.17, P = 2.81×10−8) and rs208908 (OR = 0.70, P = 4.54×10−8) were identified with different risk effect of lung cancer between men and women. Further expression quantitative trait loci and functional annotation analysis suggested rs208908 affects lung cancer risk through differential regulation of Coxsackie virus and adenovirus receptor gene expression in lung tissues between men and women. Our study is one of the first studies to provide novel insights about the genetic and molecular basis for sex disparity in lung cancer development.
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