Manufacturing Macroporous Monoliths of Microporous Metal-Organic Frameworks

We report the first use of a pressure-assisted sintering technique on metal-organic framework (MOF) powders allowing for fast production of crystalline macro-porous monoliths. Mechanical and micro-structural characterization of the monoliths is presented. The interconnected macro-porosity of the compacts can be adjusted providing an immense interface for gas-solid interaction. The sintering technique is well-established and commercially available, allowing industrial scale-up of the process

Crime and the NTE: multi-classification crime (MCC) hot spots in time and space

This paper examines crime hot spots near licensed premises in the night-time economy (NTE) to investigate whether hot spots of four different classification of crime and disorder co-occur in time and place, namely violence, disorder, drugs and criminal damage. It introduces the concept of multi-classification crime (MCC) hot spots; the presence of hot spots of more than one crime classification at the same place. Furthermore, it explores the temporal patterns of identified MCC hot spots, to determine if they exhibit distinct spatio-temporal patterns. Getis Ord (GI*) hot spot analysis was used to identify locations of statistically significant hot spots of each of the four crime and disorder classifications. Strong spatial correlations were found between licensed premises and each of the four crime and disorder classifications analysed. MCC hot spots were also identified near licensed premises. Temporal profiling of the MCC hot spots revealed all four crime types were simultaneously present in time and place, near licensed premises, on Friday through Sunday in the early hours of the morning around premise closing times. At other times, criminal damage and drugs hot spots were found to occur earlier in the evening, and disorder and violence at later time periods. Criminal damage and drug hot spots flared for shorter time periods, 2–3 h, whereas disorder and violence hot spots were present for several hours. There was a small spatial lag between Friday and Saturday, with offences occurring approximately 1 h later on Saturdays. The implications of these findings for hot spot policing are discussed

Loss of Arc renders the visual cortex impervious to the effects of sensory experience or deprivation

A myriad of mechanisms have been suggested to account for the full richness of visual cortical plasticity. We found that visual cortex lacking Arc is impervious to the effects of deprivation or experience. Using intrinsic signal imaging and chronic visually evoked potential recordings, we found that Arc−/− mice did not exhibit depression of deprived-eye responses or a shift in ocular dominance after brief monocular deprivation. Extended deprivation also failed to elicit a shift in ocular dominance or open-eye potentiation. Moreover, Arc−/− mice lacked stimulus-selective response potentiation. Although Arc−/− mice exhibited normal visual acuity, baseline ocular dominance was abnormal and resembled that observed after dark-rearing. These data suggest that Arc is required for the experience-dependent processes that normally establish and modify synaptic connections in visual cortex.Howard Hughes Medical InstituteNational Science Foundation (U.S.

T-cell responses to human papillomavirus type 16 among women with different grades of cervical neoplasia

Infection with high-risk genital human papillomavirus (HPV) types is a major risk factor for the development of cervical intraepithelial neoplasia (CIN) and invasive cervical carcinoma. The design of effective immunotherapies requires a greater understanding of how HPV-specific T-cell responses are involved in disease clearance and/or progression. Here, we have investigated T-cell responses to five HPV16 proteins (E6, E7, E4, L1 and L2) in women with CIN or cervical carcinoma directly ex vivo. T-cell responses were observed in the majority (78%) of samples. The frequency of CD4+ responders was far lower among those with progressive disease, indicating that the CD4+ T-cell response might be important in HPV clearance. CD8+ reactivity to E6 peptides was dominant across all disease grades, inferring that E6-specific CD8+ T cells are not vitally involved in disease clearance. T-cell responses were demonstrated in the majority (80%) of cervical cancer patients, but are obviously ineffective. Our study reveals significant differences in HPV16 immunity during progressive CIN. We conclude that the HPV-specific CD4+ T-cell response should be an important consideration in immunotherapy design, which should aim to target preinvasive disease

Large differences in regional precipitation change between a first and second 2 K of global warming

For adaptation and mitigation planning, stakeholders need reliable information about regional precipitation changes under different emissions scenarios and for different time periods. A significant amount of current planning effort assumes that each K of global warming produces roughly the same regional climate change. Here using 25 climate models, we compare precipitation responses with three 2 K intervals of global ensemble mean warming: a fast and a slower route to a first 2 K above pre-industrial levels, and the end-of-century difference between high-emission and mitigation scenarios. We show that, although the two routes to a first 2 K give very similar precipitation changes, a second 2 K produces quite a different response. In particular, the balance of physical mechanisms responsible for climate model uncertainty is different for a first and a second 2 K of warming. The results are consistent with a significant influence from nonlinear physical mechanisms, but aerosol and land-use effects may be important regionally

Biphasic investigation of contact mechanics in natural human hips during activities

The aim of this study was to determine the cartilage contact mechanics and the associated fluid pressurisation of the hip joint under eight daily activities, using a three-dimensional finite element hip model with biphasic cartilage layers and generic geometries. Loads with spatial and temporal variations were applied over time and the time-dependent performance of the hip cartilage during walking was also evaluated. It was found that the fluid support ratio was over 90% during the majority of the cycles for all the eight activities. A reduced fluid support ratio was observed for the time at which the contact region slid towards the interior edge of the acetabular cartilage, but these occurred when the absolute level of the peak contact stress was minimal. Over 10 cycles of gait, the peak contact stress and peak fluid pressure remained constant, but a faster process of fluid exudation was observed for the interior edge region of the acetabular cartilage. The results demonstrate the excellent function of the hip cartilage within which the solid matrix is prevented from high levels of stress during activities owing to the load shared by fluid pressurisation. The findings are important in gaining a better understanding of the hip function during daily activities, as well as the pathology of hip degeneration and potential for future interventions. They provide a basis for future subject-specific biphasic investigations of hip performance during activities

Monoclonal antibodies directed to fucoidan preparations from brown algae

Cell walls of the brown algae contain a diverse range of polysaccharides with useful bioactivities. The precise structures of the sulfated fucan/fucoidan group of polysaccharides and their roles in generating cell wall architectures and cell properties are not known in detail. Four rat monoclonal antibodies, BAM1 to BAM4, directed to sulfated fucan preparations, have been generated and used to dissect the heterogeneity of brown algal cell wall polysaccharides. BAM1 and BAM4, respectively, bind to a non-sulfated epitope and a sulfated epitope present in the sulfated fucan preparations. BAM2 and BAM3 identified additional distinct epitopes present in the fucoidan preparations. All four epitopes, not yet fully characterised, occur widely within the major brown algal taxonomic groups and show divergent distribution patterns in tissues. The analysis of cell wall extractions and fluorescence imaging reveal differences in the occurrence of the BAM1 to BAM4 epitopes in various tissues of Fucus vesiculosus. In Ectocarpus subulatus, a species closely related to the brown algal model Ectocarpus siliculosus, the BAM4 sulfated epitope was modulated in relation to salinity levels. This new set of monoclonal antibodies will be useful for the dissection of the highly complex and yet poorly resolved sulfated polysaccharides in the brown algae in relation to their ecological and economic significance

The Short-Term Effect of Weight Loss Surgery on Volumetric Breast Density and Fibroglandular Volume

Purpose: Obesity and breast density are both associated with an increased risk of breast cancer and are potentially modifiable. Weight loss surgery (WLS) causes a significant reduction in the amount of body fat and a decrease in breast cancer risk. The effect of WLS on breast density and its components has not been documented. Here, we analyze the impact of WLS on volumetric breast density (VBD) and on each of its components (fibroglandular volume and breast volume) by using three-dimensional methods. Materials and Methods: Fibroglandular volume, breast volume, and their ratio, the VBD, were calculated from mammograms before and after WLS by using Volpara™ automated software. Results: For the 80 women included, average body mass index decreased from 46.0 ± 7.22 to 33.7 ± 7.06 kg/m2. Mammograms were performed on average 11.6 ± 9.4 months before and 10.1 ± 7 months after WLS. There was a significant reduction in average breast volume (39.4 % decrease) and average fibroglandular volume (15.5 % decrease), and thus, the average VBD increased from 5.15 to 7.87 % (p < 1 × 10−9) after WLS. When stratified by menopausal status and diabetic status, VBD increased significantly in all groups but only perimenopausal and postmenopausal women and non-diabetics experienced a significant reduction in fibroglandular volume. Conclusions: Breast volume and fibroglandular volume decreased, and VBD increased following WLS, with the most significant change observed in postmenopausal women and non-diabetics. Further studies are warranted to determine how physical and biological alterations in breast density components after WLS may impact breast cancer risk.ECU Open Access Publishing Support Fun

Clinical implications of novel activating EGFR mutations in malignant peritoneal mesothelioma

<p>Abstract</p> <p>Background</p> <p>There is a paucity of information about the molecular perturbations involved in MPM tumor formation. We previously reported that EGFR-TK mutations in MPM were predictive of achieving optimal surgical cytoreduction, but the status of EGFR pathway activation potential of these mutations was not known. Here we present the mutant EGFR activating potential and the matured survival data of the EGFR mutant(mut+) relative to wild type EGFR(mut-) mesothelioma.</p> <p>Methods</p> <p>Twenty-nine patients were evaluated and their tumors were probed for mutations in the catalytic TK-domain. Twenty-five patients were treated with cytoreductive surgery and complete clinical data was available for comparison of the mut+ and mut- groups. A COS-7 cell expression model was used to determine mutation activating profiles and response to erlotinib.</p> <p>Results</p> <p>Functional mutations were found in 31%(9/29) of patients; 7 of these mutations were novel and another was the L858R mutation. All missense mutations were found to be activating mutations and responsive to erlotinib. Of the 25 patients managed surgically, there were 7 mut+ and 18 mut-. Two of 7 (29%) mut+ developed progressive disease and died with a median follow-up time of 22 months; while 13/18 (72%) mut- developed progressive disease and 10/18 (56%) died with median TTP of 12 months and median survival of 14 months.</p> <p>Conclusions</p> <p>The novel EGFR mutations identified are activating mutations responsive to erlotinib. The mut+ subset have a 'relative' improved outcome. Erlotinib may have a role in MPM and exploration for mutations in a larger patient cohort is warranted.</p