Towards scalable and controlled synthesis of metal–organic framework materials using continuous flow reactors

Metal–organic frameworks have emerged as one of the most diverse new families of materials in the past few years. Their hybrid structures, combinations of inorganic and organic moieties, give a wide range of complex architectures with resultant properties that are suitable for numerous important fields, including porosity for molecular sieving and sensing, heterogeneous catalysis, drug delivery, and energy storage. If applications of these materials are to be realised then scalable synthesis is required, taking laboratory batch reactions towards industrial production. Continuous flow reactors offer the most versatile method for scaling their solvothermal synthesis, with the largest range of materials accessible, in high yield, and with control over crystal form

Matrix concentration inequalities via the method of exchangeable pairs

This paper derives exponential concentration inequalities and polynomial moment inequalities for the spectral norm of a random matrix. The analysis requires a matrix extension of the scalar concentration theory developed by Sourav Chatterjee using Stein's method of exchangeable pairs. When applied to a sum of independent random matrices, this approach yields matrix generalizations of the classical inequalities due to Hoeffding, Bernstein, Khintchine and Rosenthal. The same technique delivers bounds for sums of dependent random matrices and more general matrix-valued functions of dependent random variables.Comment: Published in at http://dx.doi.org/10.1214/13-AOP892 the Annals of Probability (http://www.imstat.org/aop/) by the Institute of Mathematical Statistics (http://www.imstat.org

Small lakes in big landscape : multi-scale drivers of littoral ecosystem in alpine lakes.

In low nutrient alpine lakes, the littoral zone is the most productive part of the ecosystem, and it is a biodiversity hotspot. It is not entirely clear how the scale and physical heterogeneity of surrounding catchment, its ecological composition, and larger landscape gradients work together to sustain littoral communities. A total of 113 alpine lakes from the central Pyrenees were surveyed to evaluate the functional connectivity between littoral zoobenthos and landscape physical and ecological elements at geographical, catchment and local scales, and to ascertain how they affect the formation of littoral communities. At each lake, the zoobenthic composition was assessed together with geolocation, catchment hydrodynamics, geomorphology and topography, riparian vegetation composition, the presence of trout and frogs, water pH and conductivity. Multidimensional fuzzy set models integrating benthic biota and environmental variables revealed that at geographical scale, longitude unexpectedly surpassed altitude and latitude in its effect on littoral ecosystem. This reflects a sharp transition between Atlantic and Mediterranean climates and suggests a potentially high horizontal vulnerability to climate change. Topography (controlling catchment type, snow coverage and lakes connectivity) was the most influential catchment-scale driver, followed by hydrodynamics (waterbody size, type and volume of inflow/outflow). Locally, riparian plant composition significantly related to littoral community structure, richness and diversity. These variables, directly and indirectly, create habitats for aquatic and terrestrial stages of invertebrates, and control nutrient and water cycles. Three benthic associations characterised distinct lakes. Vertebrate predation, water conductivity and pH had no major influence on littoral taxa. This work provides exhaustive information from relatively pristine sites, and unveils a strong connection between littoral ecosystem and catchment heterogeneity at scales beyond the local environment. This underpins the role of alpine lakes as sensors of local and large-scale environmental changes, which can be used in monitoring networks to evaluate further impacts

Chemoattractant Signaling between Tumor Cells and Macrophages Regulates Cancer Cell Migration, Metastasis and Neovascularization

Tumor-associated macrophages are known to influence cancer progression by modulation of immune function, angiogenesis, and cell metastasis, however, little is known about the chemokine signaling networks that regulate this process. Utilizing CT26 colon cancer cells and RAW 264.7 macrophages as a model cellular system, we demonstrate that treatment of CT26 cells with RAW 264.7 conditioned medium induces cell migration, invasion and metastasis. Inflammatory gene microarray analysis indicated CT26-stimulated RAW 264.7 macrophages upregulate SDF-1α and VEGF, and that these cytokines contribute to CT26 migration in vitro. RAW 264.7 macrophages also showed a robust chemotactic response towards CT26-derived chemokines. In particular, microarray analysis and functional testing revealed CSF-1 as the major chemoattractant for RAW 264.7 macrophages. Interestingly, in the chick CAM model of cancer progression, RAW 264.7 macrophages localized specifically to the tumor periphery where they were found to increase CT26 tumor growth, microvascular density, vascular disruption, and lung metastasis, suggesting these cells home to actively invading areas of the tumor, but not the hypoxic core of the tumor mass. In support of these findings, hypoxic conditions down regulated CSF-1 production in several tumor cell lines and decreased RAW 264.7 macrophage migration in vitro. Together our findings suggest a model where normoxic tumor cells release CSF-1 to recruit macrophages to the tumor periphery where they secrete motility and angiogenic factors that facilitate tumor cell invasion and metastasis

Future research directions in pneumonia

Copyright © 2018 by the American Thoracic Society. Pneumonia is a complex pulmonary disease in need of new clinical approaches. Although triggered by a pathogen, pneumonia often results from dysregulations of host defense that likely precede infection. The coordinated activities of immune resistance and tissue resilience then dictate whether and how pneumonia progresses or resolves. Inadequate or inappropriate host responses lead to more severe outcomes such as acute respiratory distress syndrome and to organ dysfunction beyond the lungs and over extended time frames after pathogen clearance, some of which increase the risk for subsequent pneumonia. Improved understanding of such host responses will guide the development of novel approaches for preventing and curing pneumonia and for mitigating the subsequent pulmonary and extrapulmonary complications of pneumonia. The NHLBI assembled a working group of extramural investigators to prioritize avenues of host-directed pneumonia research that should yield novel approaches for interrupting the cycle of unhealthy decline caused by pneumonia. This report summarizes the working group’s specific recommendations in the areas of pneumonia susceptibility, host response, and consequences. Overarching goals include the development of more host-focused clinical approaches for preventing and treating pneumonia, the generation of predictive tools (for pneumonia occurrence, severity, and outcome), and the elucidation of mechanisms mediating immune resistance and tissue resilience in the lung. Specific areas of research are highlighted as especially promising for making advances against pneumonia

Genome-wide association study of response to cognitive-behavioural therapy in children with anxiety disorders

Background Anxiety disorders are common, and cognitive–behavioural therapy (CBT) is a first-line treatment. Candidate gene studies have suggested a genetic basis to treatment response, but findings have been inconsistent. Aims To perform the first genome-wide association study (GWAS) of psychological treatment response in children with anxiety disorders (n = 980). Method Presence and severity of anxiety was assessed using semi-structured interview at baseline, on completion of treatment (post-treatment), and 3 to 12 months after treatment completion (follow-up). DNA was genotyped using the Illumina Human Core Exome-12v1.0 array. Linear mixed models were used to test associations between genetic variants and response (change in symptom severity) immediately post-treatment and at 6-month follow-up. Results No variants passed a genome-wide significance threshold (P = 5×10−8) in either analysis. Four variants met criteria for suggestive significance (P<5×10−6) in association with response post-treatment, and three variants in the 6-month follow-up analysis. Conclusions This is the first genome-wide therapygenetic study. It suggests no common variants of very high effect underlie response to CBT. Future investigations should maximise power to detect single-variant and polygenic effects by using larger, more homogeneous cohorts

Associations between diet and disease activity in ulcerative colitis patients using a novel method of data analysis

BACKGROUND: The relapsing nature and varying geographical prevalence of ulcerative colitis (UC) implicates environmental factors such as diet in its aetiology. METHODS: In order to determine which foods might be related to disease activity in UC a new method of dietary analysis was developed and applied. Eighty-one UC patients were recruited at all stages of the disease process. Following completion of a 7 d diet diary, clinical assessment including a sigmoidoscopic examination (scale 0 (normal mucosa) to 6 (very active disease)) was conducted. Food weights for each person were adjusted (divided) by the person's calorific intake for the week. Each food consumed was given a food sigmoidoscopy score (FSS) calculated by summing the products of the (adjusted) weight of food consumed and sigmoidoscopy score for each patient and occurrence of food and dividing by the total (adjusted) weight of the food consumed by all 81 patients. Thus, foods eaten in large quantities by patients with very active disease have high FSSs and vice versa. Foods consumed by <10 people or weighing <1 kg for the whole group were excluded, leaving 75 foods. RESULTS: High FSS foods were characterized by high levels of the anti-thiamin additive sulfite (Mann-Whitney, p < 0.001), i.e. bitter, white wine, burgers, soft drinks from concentrates, sausages, lager and red wine. Caffeine also has anti-thiamin properties and decaffeinated coffee was associated with a better clinical state than the caffeine containing version. Beneficial foods (average intake per week) included pork (210 g), breakfast cereals (200 g), lettuce (110 g), apples and pears (390 g), milk (1250 ml), melon (350 g), bananas (350 g), bacon (120 g), beef and beef products (500 g), tomatoes (240 g), soup (700 g), citrus fruits (300 g), fish (290 g), yogurt (410 g), cheese (110 g), potatoes (710 g) and legumes (120 g). CONCLUSIONS: The dietary analysis method described provides a new tool for establishing relationships between diet and disease and indicates a potentially therapeutic diet for UC