Point-of-care (POC) diagnostics provide rapid actionable information for patient care at the time and site of an encounter with the health care system. The usual platform has been the lateral flow ...immunoassay. Recently, emerging molecular diagnostics have met requirements for speed, low cost, and ease of use for POC applications. A major driver for POC development is the ability to diagnose infectious diseases at sites with a limited infrastructure. The potential use in both wealthy and resource-limited settings has fueled an intense effort to build on existing technologies and to generate new technologies for the diagnosis of a broad spectrum of infectious diseases.
For more than 70 years, nitrogen-centered radicals have been recognized as potent synthetic intermediates. This review is a survey designed for use by chemists engaged in target-oriented synthesis. ...This review summarizes the recent paradigm shift in access to and application of N-centered radicals enabled by visible-light photocatalysis. This shift broadens and streamlines approaches to many small molecules because visible-light photocatalysis conditions are mild. Explicit attention is paid to innovative advances in N–X bonds as radical precursors, where X = Cl, N, S, O, and H. For clarity, key mechanistic data is noted, where available. Synthetic applications and limitations are summarized to illuminate the tremendous utility of photocatalytically generated nitrogen-centered radicals.
The allergenic load of house dust mite allergy is largely constituted by a few proteins with a hierarchical pattern of allergenicity. The serodominant specificities are the group 1&2 and the group 23 ...faecal allergens. The collective IgE binding to the group 1&2 allergens can measure unequivocal HDM sensitisation better than HDM extracts although discrepancies have been found in regions with complex acarofauna suggesting a need to investigate the specificity with allergen components. The group 4, 5, 7&21 allergens that each induce responses in about 40% of subjects are mid-tier allergens accounting for most of the remaining IgE binding. Their titres are proportional to the concomitant responses to Der p1&2. Group 2 allergen variants have different antibody binding. Body proteins only occasionally induce sensitisation although a higher prevalence of binding by atopic dermatitis patients provides a new avenue of research. A broad spectrum of IgE binding has been associated with diverse symptoms but not with the severity of asthma which is associated with low IgG antibody. Some allergens such as the group 14 large lipid binding proteins and the recently described proteins Der f 24–33, need further investigation but with the cognoscence that other denominated allergens have been found to be minor sensitisers by comparative quantitative analyses. Scabies is a confounder for diagnosis with extracts, inducing cross-reactive antibodies with Der p 4&20 as is seafood allergy with cross reactivity to Der p 10 a minor HDM allergen. The HDM genome sequence can now be used to verify allelic and paralogous variations.
Protein binding often involves conformational changes. Important questions are whether a conformational change occurs prior to a binding event ('conformational selection') or after a binding event ...('induced fit'), and how conformational transition rates can be obtained from experiments. In this article, we present general results for the chemical relaxation rates of conformational-selection and induced-fit binding processes that hold for all concentrations of proteins and ligands and, thus, go beyond the standard pseudo-first-order approximation of large ligand concentration. These results allow to distinguish conformational-selection from induced-fit processes-also in cases in which such a distinction is not possible under pseudo-first-order conditions-and to extract conformational transition rates of proteins from chemical relaxation data.
Polymorphism in the apolipoprotein E (APOE) gene is a major genetic risk determinant of late-onset Alzheimer disease (AD), with the APOE*ε4 allele conferring an increased risk and the APOE*ε2 allele ...conferring a decreased risk relative to the common APOE*ε3 allele. Strong evidence from clinical and basic research suggests that a major pathway by which APOE4 increases the risk of AD is by driving earlier and more abundant amyloid pathology in the brains of APOE*ε4 carriers. The number of amyloid-β (Aβ)-dependent and Aβ-independent pathways that are known to be differentially modulated by APOE isoforms is increasing. For example, evidence is accumulating that APOE influences tau pathology, tau-mediated neurodegeneration and microglial responses to AD-related pathologies. In addition, APOE4 is either pathogenic or shows reduced efficiency in multiple brain homeostatic pathways, including lipid transport, synaptic integrity and plasticity, glucose metabolism and cerebrovascular function. Here, we review the recent progress in clinical and basic research into the role of APOE in AD pathogenesis. We also discuss how APOE can be targeted for AD therapy using a precision medicine approach.
Cross-species comparisons of genomes, transcriptomes and gene regulation are now feasible at unprecedented resolution and throughput, enabling the comparison of human and mouse biology at the ...molecular level. Insights have been gained into the degree of conservation between human and mouse at the level of not only gene expression but also epigenetics and inter-individual variation. However, a number of limitations exist, including incomplete transcriptome characterization and difficulties in identifying orthologous phenotypes and cell types, which are beginning to be addressed by emerging technologies. Ultimately, these comparisons will help to identify the conditions under which the mouse is a suitable model of human physiology and disease, and optimize the use of animal models.
Much study has been devoted to the possible causes of an apparent decrease in the upward trend of global surface temperatures since 1998, a phenomenon that has been dubbed the global warming ..."hiatus." Here, we present an updated global surface temperature analysis that reveals that global trends are higher than those reported by the Intergovernmental Panel on Climate Change, especially in recent decades, and that the central estimate for the rate of warming during the first 15 years of the 21st century is at least as great as the last half of the 20th century. These results do not support the notion of a "slowdown" in the increase of global surface temperature.
Landsat 8, originally known as the Landsat Data Continuity Mission (LDCM), is a National Aeronautics and Space Administration (NASA)-U.S. Geological Survey (USGS) partnership that continues the ...legacy of continuous moderate resolution observations started in 1972. The conception of LDCM to the reality of Landsat 8 followed an arduous path extending over nearly 13years, but the successful launch on February 11, 2013 ensures the continuity of the unparalleled Landsat record. The USGS took over mission operations on May 30, 2013 and renamed LCDM to Landsat 8. Access to Landsat 8 data was opened to users worldwide. Three years following launch we evaluate the science and applications impact of Landsat 8. With a mission objective to enable the detection and characterization of global land changes at a scale where differentiation between natural and human-induced causes of change is possible, LDCM promised incremental technical improvements in capabilities needed for Landsat scientific and applications investigations. Results show that with Landsat 8, we are acquiring more data than ever before, the radiometric and geometric quality of data are generally technically superior to data acquired by past Landsat missions, and the new measurements, e.g., the coastal aerosol and cirrus bands, are opening new opportunities. Collectively, these improvements are sparking the growth of science and applications opportunities. Equally important, with Landsat 7 still operational, we have returned to global imaging on an 8-daycycle, a capability that ended when Landsat 5 ceased operational Earth imaging in November 2011. As a result, the Landsat program is on secure footings and planning is underway to extend the record for another 20 or more years.
•Landsat Data Continuity Mission (Landsat 8) was launched February 11, 2013.•22 manuscripts highlight the science impacts of Landsat 8.•Landsat 8 is acquiring more data than ever before.•Radiometric and geometric quality are superior to previous Landsat data.•New bands, e.g., coastal aerosol and cirrus, create new applications opportunities.
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