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https://www.readbyqxmd.com/read/28213810/how-to-tackle-natural-focal-infections-from-risk-assessment-to-vaccination-strategies
#1
Luca Busani, Alexander E Platonov, Onder Ergonul, Giovanni Rezza
Natural focal diseases are caused by biological agents associated with specific landscapes. The natural focus of such diseases is defined as any natural ecosystem containing the pathogen's population as an essential component. In such context, the agent circulates independently on human presence, and humans may become accidentally infected through contact with vectors or reservoirs. Some viruses (i.e., tick-borne encephalitis and Congo-Crimean hemorrhagic fever virus) are paradigmatic examples of natural focal diseases...
February 18, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28212305/epigenetic-landscape-during-coronavirus-infection
#2
Alexandra Schäfer, Ralph S Baric
Coronaviruses (CoV) comprise a large group of emerging human and animal pathogens, including the highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) strains. The molecular mechanisms regulating emerging coronavirus pathogenesis are complex and include virus-host interactions associated with entry, replication, egress and innate immune control. Epigenetics research investigates the genetic and non-genetic factors that regulate phenotypic variation, usually caused by external and environmental factors that alter host expression patterns and performance without any change in the underlying genotype...
February 15, 2017: Pathogens
https://www.readbyqxmd.com/read/28211491/interference-between-variants-of-peach-latent-mosaic-viroid-reveals-novel-features-of-its-fitness-landscape-implications-for-detection
#3
Pedro Serra, Edson Bertolini, M Carmen Martínez, Mariano Cambra, Ricardo Flores
Natural populations of peach latent mosaic viroid (PLMVd) are complex mixtures of variants. During routine testing, TaqMan rtRT-PCR and RNA gel-blot hybridization produced discordant results with some PLMVd isolates. Analysis of the corresponding populations showed that they were exclusively composed of variants (of class II) with a structural domain different from that of the reference and many other variants (of class I) targeted by the TaqMan rtRT-PCR probe. Bioassays in peach revealed that a representative PLMVd variant of class II replicated without symptoms, generated a progeny with low nucleotide diversity, and, intriguingly, outcompeted a representative symptomatic variant of class I when co-inoculated in equimolecular amounts...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28209558/readiness-for-delivering-digital-health-at-scale-lessons-from-a-longitudinal-qualitative-evaluation-of-a-national-digital-health-innovation-program-in-the-united-kingdom
#4
Marilyn R Lennon, Matt-Mouley Bouamrane, Alison M Devlin, Siobhan O'Connor, Catherine O'Donnell, Ula Chetty, Ruth Agbakoba, Annemieke Bikker, Eleanor Grieve, Tracy Finch, Nicholas Watson, Sally Wyke, Frances S Mair
BACKGROUND: Digital health has the potential to support care delivery for chronic illness. Despite positive evidence from localized implementations, new technologies have proven slow to become accepted, integrated, and routinized at scale. OBJECTIVE: The aim of our study was to examine barriers and facilitators to implementation of digital health at scale through the evaluation of a £37m national digital health program: ‟Delivering Assisted Living Lifestyles at Scale" (dallas) from 2012-2015...
February 16, 2017: Journal of Medical Internet Research
https://www.readbyqxmd.com/read/28196882/trade-offs-between-enzyme-fitness-and-solubility-illuminated-by-deep-mutational-scanning
#5
Justin R Klesmith, John-Paul Bacik, Emily E Wrenbeck, Ryszard Michalczyk, Timothy A Whitehead
Proteins are marginally stable, and an understanding of the sequence determinants for improved protein solubility is highly desired. For enzymes, it is well known that many mutations that increase protein solubility decrease catalytic activity. These competing effects frustrate efforts to design and engineer stable, active enzymes without laborious high-throughput activity screens. To address the trade-off between enzyme solubility and activity, we performed deep mutational scanning using two different screens/selections that purport to gauge protein solubility for two full-length enzymes...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28195238/the-changing-landscape-of-clinical-trial-and-approval-processes-in-china
#6
REVIEW
Qing Zhou, Xiao-Yuan Chen, Zhi-Min Yang, Yi-Long Wu
In the past decade, the standards of clinical trials in China have moved closer to international standards, thus encouraging the development of innovative drugs. However, a large backlog of pending applications for both drug approval and clinical trial registration has arisen owing to the complexity of the approval process, the volume of applications and a lack of staff available to process these applications, among other reasons. To improve the drug approval process, a 'four-colour-light' strategy was introduced...
February 14, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28193376/radiology-research-in-quality-and-safety-current-trends-and-future-needs
#7
REVIEW
Matthew E Zygmont, Jason N Itri, Andrew B Rosenkrantz, Phuong-Anh T Duong, Lori Mankowski Gettle, Mishal Mendiratta-Lala, Elena P Scali, Ronald S Winokur, Linda Probyn, Justin W Kung, Eric Bakow, Nadja Kadom
Promoting quality and safety research is now essential for radiology as reimbursement is increasingly tied to measures of quality, patient safety, efficiency, and appropriateness of imaging. This article provides an overview of key features necessary to promote successful quality improvement efforts in radiology. Emphasis is given to current trends and future opportunities for directing research. Establishing and maintaining a culture of safety is paramount to organizations wishing to improve patient care. The correct culture must be in place to support quality initiatives and create accountability for patient care...
March 2017: Academic Radiology
https://www.readbyqxmd.com/read/28187280/cancer-clinical-trials-the-rear-view-mirror-and-the-crystal-ball
#8
Dave Cescon, Lillian L Siu
Clinical trials are key to translating scientific advances into progress in cancer research and care. Confronted by developments in basic science, the landscape of clinical cancer research is rapidly evolving. Here, we review recent changes in clinical trials' design and conduct, and we forecast future directions toward personalized and global impact.
February 9, 2017: Cell
https://www.readbyqxmd.com/read/28186772/the-thermodynamics-of-restoring-underwater-superhydrophobicity
#9
Paul R Jones, Adrian Thomas Kirn, David Ma, Dennis T Rich, Neelesh Ashok Patankar
Superhydrophobic surfaces submerged in liquids are susceptible to permanently becoming wet. This is especially true when the ambient liquid is pressurized or undersaturated with air. To gain insight into the thermodynamics of restoring underwater superhydrophobicity, nucleation theory is applied to the design of spontaneously dewetting conical pores. It is found that for intrinsically hydrophobic materials, there is a geometric constraint for which reversible superhydrophobic behavior may occur. Molecular dynamics simulations are implemented to support the theory, and steered molecular dynamics simulations are used to investigate the energy landscape of the dewetting process...
February 10, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28186344/non-covalent-interactions-and-internal-dynamics-in-pyridine-ammonia-a-combined-quantum-chemical-and-microwave-spectroscopy-study
#10
Lorenzo Spada, Nicola Tasinato, Fanny Vazart, Vincenzo Barone, Walther Caminati, Cristina Puzzarini
The 1:1 complex of ammonia with pyridine has been characterized by using state-of-the-art quantum-chemical computations combined with pulsed-jet Fourier-Transform microwave spectroscopy. The computed potential energy landscape pointed out the formation of a stable σ-type complex, which has been confirmed experimentally: the analysis of the rotational spectrum showed the presence of only one 1:1 pyridine - ammonia adduct. Each rotational transition is split into several components due to the internal rotation of NH₃ around its C₃ axis and to the hyperfine structure of both ¹⁴N quadrupolar nuclei, thus providing the unequivocal proof that the two molecules form a σ-type complex involving both a N-H···N and a C-H···N hydrogen bond...
February 10, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28179143/how-s-the-flu-getting-through-landscape-genetics-suggests-both-humans-and-birds-spread-h5n1-in-egypt
#11
Sean G Young, Margaret Carrel, Andrew Kitchen, George P Malanson, James Tamerius, Mohamad Ali, Ghazi Kayali
First introduced to Egypt in 2006, H5N1 highly pathogenic avian influenza has resulted in the death of millions of birds and caused over 350 infections and at least 117 deaths in humans. After a decade of viral circulation, outbreaks continue to occur and diffusion mechanisms between poultry farms remain unclear. Using landscape genetics techniques, we identify the distance models most strongly correlated with the genetic relatedness of the viruses, suggesting the most likely methods of viral diffusion within Egyptian poultry...
February 4, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28178805/atomic-clusters-with-addressable-complexity
#12
David J Wales
A general formulation for constructing addressable atomic clusters is introduced, based on one or more reference structures. By modifying the well depths in a given interatomic potential in favour of nearest-neighbour interactions that are defined in the reference(s), the potential energy landscape can be biased to make a particular permutational isomer the global minimum. The magnitude of the bias changes the resulting potential energy landscape systematically, providing a framework to produce clusters that should self-organise efficiently into the target structure...
February 7, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28177620/transforming-the-energy-landscape-of-a-coiled-coil-peptide-via-point-mutations
#13
Konstantin Röder, David J Wales
We analyze the effect of point mutations on the energy landscape of a coiled-coil peptide, GCN4-pLI, where the native state is a parallel tetrameric configuration formed from two identical dimers. Experimentally, a single mutation, E20S, supports both antiparallel and parallel structures. Here, we analyze the potential energy landscapes of the dimeric units for the parent sequence and four mutants, namely E20S, E20A, E20P, and E20G. Despite sharing characteristic funnels containing the parallel and antiparallel structures, the point mutations change some parts of the landscape quite dramatically, and we predict new intermediate structures and characterize the associated heat capacities...
February 8, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28171704/subdivision-design-and-stewardship-affect-bird-and-mammal-use-of-conservation-developments
#14
Cooper M Farr, Liba Pejchar, Sarah E Reed
Developing effective tools for conservation on private lands is increasingly important for global biodiversity conservation; private lands are located in more productive and biologically diverse areas, and they face accelerated rates of land conversion. One strategy is conservation development (CD) subdivisions, which cluster houses in a small portion of a property and preserve the remaining land as protected open space. Despite widespread use, the characteristics that make CD more or less effective at achieving biodiversity conservation are not well understood...
February 7, 2017: Ecological Applications: a Publication of the Ecological Society of America
https://www.readbyqxmd.com/read/28169993/the-evolving-genomic-landscape-of-urothelial-carcinoma
#15
REVIEW
Alexander P Glaser, Damiano Fantini, Ali Shilatifard, Edward M Schaeffer, Joshua J Meeks
Survival of patients with urothelial carcinoma (including bladder cancer and upper tract urothelial carcinoma) is limited by our current approaches to staging, surgery, and chemotherapy. Large-scale, next-generation sequencing collaborations, such as The Cancer Genome Atlas, have already identified drivers and vulnerabilities of urothelial carcinoma. This disease has a high degree of mutational heterogeneity and a high frequency of somatic mutations compared with other solid tumours, potentially resulting in an increased neoantigen burden...
February 7, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/28166060/metamaterial-plasmonic-and-nanophotonic-devices
#16
Francesco Monticone, Andrea Alù
The field of metamaterials has opened landscapes of possibilities in basic science, and a paradigm shift in the way we think about and design emergent material properties. In many scenarios, metamaterial concepts have helped overcome long-held scientific challenges, such as the absence of optical magnetism and the limits imposed by diffraction in optical imaging. As the potential of metamaterials, as well as their limitations, become clearer, these advances in basic science have started to make an impact on several applications in different areas, with far-reaching implications for many scientific and engineering fields...
February 6, 2017: Reports on Progress in Physics
https://www.readbyqxmd.com/read/28165730/kinetic-pathway-of-3-helix-micelle-formation
#17
JooChuan Ang, Benson T Jung, He Dong, Ting Xu
A subtle but highly pertinent factor in the self-assembly of hierarchical nanostructures is the kinetic landscape. Self-assembly of a hierarchical multicomponent system requires the intricate balance of noncovalent interactions on a similar energy scale that can result in several self-assembly processes occurring at different time scales. We seek to understand the hierarchical assemblies within an amphiphilic 3-helix peptide-PEG-lipid conjugate system in the formation process of highly stable 3-helix micelles (3HMs)...
February 15, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28161773/clinicopathological-differences-exist-between-calr-and-jak2-mutated-myeloproliferative-neoplasms-despite-a-similar-molecular-landscape-data-from-targeted-next-generation-sequencing-in-the-diagnostic-laboratory
#18
Rishu Agarwal, Piers Blombery, Michelle McBean, Kate Jones, Andrew Fellowes, Ken Doig, Cecily Forsyth, David A Westerman
Mutations in CALR have recently been detected in JAK2-negative myeloproliferative neoplasms (MPNs) and are key pathological drivers in these diseases. CALR-mutated MPNs are shown to have numerous clinicopathological differences to JAK2-mutated MPNs. The basis of these differences is poorly understood. It is unknown whether these differences result directly from any differences in intracellular signalling abnormalities induced by JAK2/CALR mutations or whether they relate to other phenomena such as a differing spectrum of genetic lesions between the two groups...
February 4, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28160697/sources-and-mechanisms-of-nitrate-and-orthophosphate-transport-in-urban-stormwater-runoff-from-residential-catchments
#19
Yun-Ya Yang, Gurpal S Toor
Nutrients export from residential catchments contributes to water quality impairment in urban water bodies. We investigated the concentrations, transport mechanisms, and sources of nitrate-nitrogen (NO3-N) and orthophosphate-phosphorus (PO4-P) in urban stormwater runoff generated in residential catchments in Tampa Bay, Florida, United States. Street runoff samples, collected over 21 storm events, were supplemented with rainfall and roof runoff samples from six representative residential catchments. Samples were analyzed for N and P forms, N and oxygen (O) isotopes of nitrate (δ(18)O-NO3(-) and δ(15)N-NO3(-)), and δ(18)O and hydrogen (δD) isotopes of water (H2O)...
January 25, 2017: Water Research
https://www.readbyqxmd.com/read/28159928/a-meta-analysis-of-hla-peptidome-composition-in-different-hematological-entities-entity-specific-dividing-lines-and-pan-leukemia-antigens
#20
Linus Backert, Daniel Johannes Kowalewski, Simon Walz, Heiko Schuster, Claudia Berlin, Marian Christoph Neidert, Mirle Schemionek, Tim H Brümmendorf, Vladan Vucinic, Dietger Niederwieser, Lothar Kanz, Helmut Rainer Salih, Oliver Kohlbacher, Katja Weisel, Hans-Georg Rammensee, Stefan StevanoviÄ, Juliane Sarah Walz
Hematological malignancies (HM) are highly amenable targets for immunotherapeutic intervention and may be effectively treated by antigen-specific T-cell based treatment. Recent studies demonstrate that physiologically occurring anti-cancer T-cell responses in certain HM entities target broadly presented non-mutated epitopes. HLA ligands are thus implied as prime targets for broadly applicable and antigen-specific off-the-shelf compounds. With the aim of assessing the presence of common targets shared among different HM which may enable addressing a larger patient collective we conducted a meta-analysis of 83 mass spectrometry-based HLA peptidome datasets (comprising 40,361 unique peptide identifications) across four major HM (19 AML, 16 CML, 35 CLL, and 13 MM/MCL samples) and investigated similarities and differences within the HLA presented antigenic landscape...
January 31, 2017: Oncotarget
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