403 research outputs found
Regioselective Oxidative Arylation of Indoles Bearing N-Alkyl Protecting Groups: Dual CâH Functionalization via a Concerted MetalationâDeprotonation Mechanism
The most direct method for synthesizing 2-arylindoles is oxidative coupling of an arene with an indole. We have shown that both the activity and regioselectivity of this cross-coupling reaction are correlated with the acidity of the medium. This insight has been applied to predict the best conditions for the oxidative cross-coupling of N-alkylindoles, an important class of substrates that has heretofore been incompatible with the harsh conditions required for oxidative cross-coupling. Both experimental and computational data indicate that the mechanism for CâH palladation of both the indoles and simple arenes is best described as concerted metalationâdeprotonation, regardless of the substitution on the arene
Photon assisted Levy flights of minority carriers in n-InP
We study the photoluminescence spectra of n-doped InP bulk wafers, both in
the reflection and the transmission geometries relative to the excitation beam.
From the observed spectra we estimate the spatial distribution of minority
carriers allowing for the spectral filtering due to re-absorption of
luminescence in the wafer. This distribution unambiguously demonstrates a
non-exponential drop-off with distance from the excitation region. Such a
behavior evidences an anomalous photon-assisted transport of minority carriers
enhanced owing to the high quantum efficiency of emission. It is shown that the
transport conforms very well to the so-called Levy-flights process
corresponding to a peculiar random walk that does not reduce to diffusion. The
index gamma of the Levy flights distribution is found to be in the range gamma
= 0.64 to 0.79, depending on the doping. Thus, we propose the high-efficiency
direct-gap semiconductors as a remarkable laboratory system for studying the
anomalous transport.Comment: 12 pages, 9 figure
Implications of carbon cycle steady state assumption for biogeochemical modeling performance and inverse parameter retrieval
We analyze the impacts of the steady state assumption on inverse model parameter
retrieval from biogeochemical models. An inverse model parameterization study using
eddy covariance CO2 flux data was performed with the Carnegie Ames Stanford
Approach (CASA) model under conditions of strict and relaxed carbon cycle steady state
assumption (CCSSA) in order to evaluate both the robustness of the modelâs structure for
the simulation of net ecosystem carbon fluxes and the assessment of the CCSSA
effects on simulations and parameter estimation. Net ecosystem production (NEP)
measurements from several eddy covariance sites were compared with NEP estimates
from the CASA model driven by local weather station climate inputs as well as by
remotely sensed fraction of photosynthetically active radiation absorbed by vegetation
and leaf area index. The parameters considered for optimization are directly related to
aboveground and belowground modeled responses to temperature and water availability,
as well as a parameter (h) that relaxed the CCSSA in the model, allowing for site level
simulations to be initialized either as net sinks or sources. A robust relationship was
observed between NEP observations and predictions for most of the sites through the
range of temporal scales considered (daily, weekly, biweekly, and monthly), supporting
the conclusion that the model structure is able to capture the main processes explaining
NEP variability. Overall, relaxing CCSSA increased model efficiency (21%) and
decreased normalized average error ( 92%). Intersite variability was a major source of
variance in model performance differences between fixed (CCSSAf) and relaxed
(CCSSAr) CCSSA conditions. These differences were correlated with mean annual NEP
observations, where an average increase in modeling efficiency of 0.06 per 100 g Cm 2 a 1
(where a is years) of NEP is observed (a < 0.003). The parameter h was found to
be a key parameter in the optimization exercise, generating significant model efficiency
losses when removed from the initial parameter set and parameter uncertainties were
significantly lower under CCSSAr. Moreover, modeled soil carbon stocks were generally
closer to observations once the steady state assumption was relaxed. Finally, we also show
that estimates of individual parameters are affected by the steady state assumption. For
example, estimates of radiation-use efficiency were strongly affected by the CCSSAf
indicating compensation effects for the inadequate steady state assumption, leading to effective and thus biased parameters. Overall, the importance of model structural evaluation
in data assimilation approaches is thus emphasize
The phenome analysis of mutant alleles in Leucine-Rich Repeat Receptor-Like Kinase genes in rice reveals new potential targets for stress tolerant cereals
AbstractPlants are constantly exposed to a variety of biotic and abiotic stresses that reduce their fitness and performance. At the molecular level, the perception of extracellular stimuli and the subsequent activation of defense responses require a complex interplay of signaling cascades, in which protein phosphorylation plays a central role. Several studies have shown that some members of the Leucine-Rich Repeat Receptor-Like Kinase (LRR-RLK) family are involved in stress and developmental pathways. We report here a systematic analysis of the role of the members of this gene family by mutant phenotyping in the monocotyledon model plant rice, Oryza sativa. We have then targeted 176 of the âŒ320 LRR-RLK genes (55.7%) and genotyped 288 mutant lines. Position of the insertion was confirmed in 128 lines corresponding to 100 LRR-RLK genes (31.6% of the entire family). All mutant lines harboring homozygous insertions have been screened for phenotypes under normal conditions and under various abiotic stresses. Mutant plants have been observed at several stages of growth, from seedlings in Petri dishes to flowering and grain filling under greenhouse conditions. Our results show that 37 of the LRR-RLK rice genes are potential targets for improvement especially in the generation of abiotic stress tolerant cereals
Monitoring Healthy Metabolic Trajectories with Nutritional Metabonomics
Metabonomics is a well established analytical approach for the analysis of physiological regulatory processes via the metabolic profiling of biofluids and tissues in living organisms. Its potential is fully exploited in the field of ânutrimetabonomicsâ that aims at assessing the metabolic effects of active ingredients and foods in individuals. Yet, one of the greatest challenges in nutrition research is to decipher the critical interactions between mammalian organisms and environmental factors, including the gut microbiota. âNutrimetabonomicsâ is today foreseen as a powerful approach for future nutritional programs tailored at health maintenance and disease prevention
Septins Recognize and Entrap Dividing Bacterial Cells for Delivery to Lysosomes.
The cytoskeleton occupies a central role in cellular immunity by promoting bacterial sensing and antibacterial functions. Septins are cytoskeletal proteins implicated in various cellular processes, including cell division. Septins also assemble into cage-like structures that entrap cytosolic Shigella, yet how septins recognize bacteria is poorly understood. Here, we discover that septins are recruited to regions of micron-scale membrane curvature upon invasion and division by a variety of bacterial species. Cardiolipin, a curvature-specific phospholipid, promotes septin recruitment to highly curved membranes of Shigella, and bacterial mutants lacking cardiolipin exhibit less septin cage entrapment. Chemically inhibiting cell separation to prolong membrane curvature or reducing Shigella cell growth respectively increases and decreases septin cage formation. Once formed, septin cages inhibit Shigella cell division upon recruitment of autophagic and lysosomal machinery. Thus, recognition of dividing bacterial cells by the septin cytoskeleton is a powerful mechanism to restrict the proliferation of intracellular bacterial pathogens
New directions for patient-centred care in scleroderma : the Scleroderma Patient-centred Intervention Network (SPIN)
Systemic sclerosis (SSc), or scleroderma,
is a chronic multisystem autoimmune
disorder characterised by
thickening and fibrosis of the skin and
by the involvement of internal organs
such as the lungs, kidneys, gastrointestinal
tract, and heart. Because there is
no cure, feasibly-implemented and easily
accessible evidence-based interventions
to improve health-related quality
of life (HRQoL) are needed. Due to a
lack of evidence, however, specific recommendations
have not been made
regarding non-pharmacological interventions
(e.g. behavioural/psychological,
educational, physical/occupational
therapy) to improve HRQoL in SSc. The
Scleroderma Patient-centred Intervention
Network (SPIN) was recently organised
to address this gap. SPIN is
comprised of patient representatives,
clinicians, and researchers from Canada,
the USA, and Europe. The goal
of SPIN, as described in this article, is
to develop, test, and disseminate a set
of accessible interventions designed to
complement standard care in order to
improve HRQoL outcomes in SSc.The initial organisational meeting for SPIN was funded by a Canadian Institutes of Health Research (CIHR) Meetings, Planning, and Dissemination grant to B.D. Thombs (KPE-109130), Sclerodermie Quebec, and the Lady Davis Institute for Medical Research of the Jewish General Hospital, Montreal, Quebec. SPIN receives finding support from the Sclemderma Society of Ontario, the Scleroderma Society of Canada, and Sclerodermie Quebec. B.D. Thombs and M. Hudson are supported by New Investigator awards from the CIHR, and Etablissement de Jeunes Chercheurs awards from the Fonds de la Recherche en Sante Quebec (FRSQ). M. Baron is the director of the Canadian Scleroderma Research Group, which receives grant folding from the CIHR, the Scleroderma Society of Canada and its provincial chapters, Scleroderma Society of Ontario, Sclerodermie Quebec, and the Ontario Arthritis Society, and educational grants from Actelion Pharmaceuticals and Pfizer. M.D. Mayes and S. Assassi are supported by the NIH/NIAMS Scleroderma Center of Research Translation grant no. P50-AR054144. S.J. Motivala is supported by an NIH career development grant (K23 AG027860) and the UCLA Cousins Center for Psychoneuroimmunology. D. Khanna is supported by a NIH/NIAMS K23 AR053858-04) and NIH/NIAMS U01 AR057936A, the National Institutes of Health through the NIH Roadmap for Medical Research Grant (AR052177), and has served as a consultant or on speakers bureau for Actelion, BMS, Gilead, Pfizer, and United Therapeutics
The Scleroderma Patient-centered Intervention Network (SPIN) Cohort : protocol for a cohort multiple randomised controlled trial (cmRCT) design to support trials of psychosocial and rehabilitation interventions in a rare disease context
Introduction: Psychosocial and rehabilitation
interventions are increasingly used to attenuate disability and improve health-related quality of life (HRQL) in chronic diseases, but are typically not available for patients with rare diseases. Conducting rigorous, adequately powered trials of these interventions for patients with rare diseases is difficult. The Scleroderma Patient-centered Intervention Network (SPIN) is an international collaboration of patient organisations, clinicians and researchers. The aim of SPIN is to develop a research infrastructure to test accessible, low-cost self-guided online interventions to reduce disability and improve HRQL for people living with the rare disease systemic sclerosis (SSc or scleroderma). Once tested, effective interventions will be made accessible through patient organisations partnering with SPIN. Methods and analysis: SPIN will employ the cohort multiple randomised controlled trial (cmRCT) design, in which patients consent to participate in a cohort for ongoing data collection. The aim is to recruit 1500â 2000 patients from centres across the world within a period of 5 years (2013â2018). Eligible participants are persons â„18 years of age with a diagnosis of SSc. In addition to baseline medical data, participants will complete patient-reported outcome measures every 3 months. Upon enrolment in the cohort, patients will consent to be contacted in the future to participate in intervention research and to allow their data to be used for comparison purposes for interventions tested with other cohort participants. Once nterventions are developed, patients from the cohort will be randomly selected and offered interventions as part of pragmatic
RCTs. Outcomes from patients offered interventions will be compared with outcomes from trial-eligible patients who are not offered the interventions.
Ethics and dissemination: The use of the cmRCT design, the development of self-guided online interventions and partnerships with patient organisations will allow SPIN to develop, rigourously test and effectively disseminate psychosocial and rehabilitation interventions for people with SSc.(undefined
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