648 research outputs found
On-site earthquake early warning: a partially non-ergodic perspective from the site effects point of view
We introduce in the on-site earthquake early warning (EEW) a partially non-ergodic perspective
from the site effects point of view. We consider the on-site EEW approach where the peak
ground velocity (PGV) for S waves is predicted from an early estimate, over the P waves,
of either the peak-displacement (PD) or cumulative squared velocity (IV2). The empirical
PD-PGV and IV2-PGV relationships are developed by applying a mixed-effect regression
where the site-specific modifications of ground shaking are treated as random effects. We
considered a large data set composed of almost 31 000 selected recordings in central Italy, a
region struck by four earthquakes with magnitude between 6 and 6.5 since the 2009 L’Aquila
earthquake. We split the data set into three subsets used for calibrating and validating the
on-site EEW models, and for exemplifying their application to stations installed after the
calibration phase. We show that the partially non-ergodic models improve the accuracy of
the PGV predictions with respect to ergodic models derived for other regions of the world.
Moreover, considering PD and accounting for site effects, we reduce the (apparent) aleatory
variability of the logarithm of PGV from 0.31 to 0.36, typical values for ergodic on-site EEW
models, to about 0.25. Interestingly, a lower variability of 0.15 is obtained by considering IV2
as proxy, which suggests further consideration of this parameter for the design of on-site EEW
systems. Since being site-specific is an inherent characteristic of on-site EEW applications,
the improved accuracy and precision of the PGV predicted for a target protection translate in
a better customization of the alert protocols for automatic actions
Directed mutational scanning reveals a balance between acidic and hydrophobic residues in strong human activation domains
Acidic activation domains are intrinsically disordered regions of the transcription factors that bind coactivators. The intrinsic disorder and low evolutionary conservation of activation domains have made it difficult to identify the sequence features that control activity. To address this problem, we designed thousands of variants in seven acidic activation domains and measured their activities with a high-throughput assay in human cell culture. We found that strong activation domain activity requires a balance between the number of acidic residues and aromatic and leucine residues. These findings motivated a predictor of acidic activation domains that scans the human proteome for clusters of aromatic and leucine residues embedded in regions of high acidity. This predictor identifies known activation domains and accurately predicts previously unidentified ones. Our results support a flexible acidic exposure model of activation domains in which the acidic residues solubilize hydrophobic motifs so that they can interact with coactivators. A record of this paper\u27s transparent peer review process is included in the supplemental information
Sacrificial Ionic Bonds Need To Be Randomly Distributed To Provide Shear Deformability
Multivalent ions are known to allow for reversible cross-linking in soft biological materials, providing stiffness and extensibility via sacrificial bonds. We present a simple model where stiff nanoscale elements carrying negative charges are coupled in shear by divalent mobile cations in aqueous media. Such a shear coupling through a soft glue has, indeed, been proposed to operate in biological nanocomposites. While the coupling is elastic and brittle when the negative charges are periodically arranged, sufficient randomness in their distribution allows for large irreversible deformation. Dependent on their function, biological as well as technical materials have to possess different, often contradictory, properties. In load-bearing materials, such as bone, a high stiffness has to be reconciled with an elevated toughness. A high stiffness, defined as the initial slope of the stress-strain curve, means that the material deforms only little with applied load. On the other hand, toughness is a measure of how much energy has to be put into the material to break it. In one-component materials, stiffness and toughness are typically contradictory properties. A strategy often followed by natur
Preparation of amino-substituted indenes and 1,4-dihydronaphthalenes using a one-pot multireaction approach: total synthesis of oxybenzo[c]phenanthridine alkaloids
Allylic trichloroacetimidates bearing a 2-vinyl or 2-allylaryl group have been designed as substrates for a one-pot, two-step multi-bond-forming process leading to the general preparation of aminoindenes and amino-substituted 1,4-dihydronaphthalenes. The synthetic utility of the privileged structures formed from this one-pot process was demonstrated with the total synthesis of four oxybenzo[c]phenanthridine alkaloids, oxychelerythrine, oxysanguinarine, oxynitidine, and oxyavicine. An intramolecular biaryl Heck coupling reaction, catalyzed using the Hermann–Beller palladacycle was used to effect the key step during the synthesis of the natural products
Applications of raman spectroscopy in dentistry part II: Soft tissue analysis
Raman spectroscopy is rapidly moving from an experimental technique for the analysis of biological molecules to a tool for the real-time clinical diagnosis and in situ evaluation of the oral tissue in medical and dental research. The purpose of this study is to identify various applications of Raman spectroscopy, to evaluate the contemporary status and to explore future directions in the field of dentistry. Several in-depth applications are presented to illustrate Raman spectroscopy in early diagnosis of soft tissue abnormalities. Raman spectroscopy allows to analyze histological and biochemical composition of biological tissues. The technique not only demonstrates its role in the disclosure of dysplasia and malignancy but also in performing guided biopsies, diagnosing sialoliths, and assessment of surgical margins. Raman spectroscopy is used to identify the molecular structures and its components to give substantial information about the chemical structure properties of these molecules. In this paper, we acquaint the utilization of Raman spectroscopy in analyzing the soft tissues in relation to dentistry
Creating a pandemic of health: Big ideas for a new initiative on global health equity and innovation
Global delivery models: the role of talent, speed and time zones in the global outsourcing industry
Global delivery models (GDMs) are transforming the global IT and business process outsourcing industry. GDMs are a new form of client-specific investment promoting service integration with clients by combining client proximity with time-zone spread for 24/7 service operations. We investigate antecedents and contingencies of setting up GDM structures. Based on comprehensive data we show that providers are likely to establish GDM location configurations when clients value access to globally distributed talent and speed of service delivery, in particular when services are highly commoditized. Findings imply that coordination across time zones increasingly affects international operations in business-to-business and born-global industries
Skeletal Diversification via Heteroatom Linkage Control: Preparation of Bicyclic and Spirocyclic Scaffolds from NSubstituted Homopropargyl Alcohols
The discovery and application of a new branching pathway synthesis strategy that rapidly produces skeletally diverse scaffolds is described. Two different scaffold types, one a bicyclic iodo-vinylidene tertiary amine/tertiary alcohol and the other, a spirocyclic 3-furanone, are each obtained using a two-step sequence featuring a common first step. Both scaffold types lead to intermediates that can be orthogonally diversified using the same final components. One of the scaffold types was obtained in sufficiently high yield that it was immediately used to produce a 97-compound library
For money or service? a cross-sectional survey of preference for financial versus non-financial rural practice characteristics among ghanaian medical students
Abstract
Background
Health worker shortage and maldistribution are among the biggest threats to health systems in Africa. New medical graduates are prime targets for recruitment to deprived rural areas. However, little research has been done to determine the influence of workers' background and future plans on their preference for rural practice incentives and characteristics. The purpose of this study was to identify determinants of preference for rural job characteristics among fourth year medical students in Ghana.
Methods
We asked fourth-year Ghanaian medical students to rank the importance of rural practice attributes including salary, infrastructure, management style, and contract length in considering future jobs. We used bivariate and multivariate ordinal logistic regression to estimate the association between attribute valuation and students' socio-demographic background, educational experience, and future career plans.
Results
Of 310 eligible fourth year medical students, complete data was available for 302 students (97%). Students considering emigration ranked salary as more important than students not considering emigration, while students with rural living experience ranked salary as less important than those with no rural experience. Students willing to work in a rural area ranked infrastructure as more important than students who were unwilling, while female students ranked infrastructure as less important than male students. Students who were willing to work in a rural area ranked management style as a more important rural practice attribute than those who were unwilling to work in a rural area. Students studying in Kumasi ranked contract length as more important than those in Accra, while international students ranked contract length as less important than Ghanaian students.
Conclusions
Interventions to improve rural practice conditions are likely to be more persuasive than salary incentives to Ghanaian medical students who are willing to work in rural environments a priori. Policy experiments should test the impact of these interventions on actual uptake by students upon graduation.http://deepblue.lib.umich.edu/bitstream/2027.42/112499/1/12913_2011_Article_1837.pd
An in vitro evaluation of epigallocatechin gallate (eGCG) as a biocompatible inhibitor of ricin toxin
The catechin, epigallocatechin gallate (eGCG), found in green tea, has inhibitory activity against a number of protein toxins and was investigated in relation to its impact upon ricin toxin (RT) in vitro. The IC50 for RT was 0.08 ± 0.004 ng/mL whereas the IC50 for RT + 100 μM eGCG was 3.02 ± 0.572 ng/mL, indicating that eGCG mediated a significant (p < 0.0001) reduction in ricin toxicity. This experiment was repeated in the human macrophage cell line THP-1 and IC50 values were obtained for RT (0.54 ± 0.024 ng/mL) and RT + 100 μM eGCG (0.68 ± 0.235 ng/mL) again using 100 μM eGCG and was significant (p = 0.0013). The documented reduction in ricin toxicity mediated by eGCG was found to be eGCG concentration dependent, with 80 and 100 μg/mL (i.e. 178 and 223 μM respectively) of eGCG mediating a significant (p = 0.0472 and 0.0232) reduction in ricin toxicity at 20 and 4 ng/ml of RT in Vero and THP-1 cells (respectively). When viability was measured in THP-1 cells by propidium iodide exclusion (as opposed to the MTT assays used previously) 10 ng/mL and 5 ng/mL of RT was used. The addition of 1000 μM and 100 μM eGCG mediated a significant (p = 0.0015 and < 0.0001 respectively) reduction in ricin toxicity relative to an identical concentration of ricin with 1 μg eGCG. Further, eGCG (100 μM) was found to reduce the binding of RT B chain to lactose-conjugated Sepharose as well as significantly (p = 0.0039) reduce the uptake of RT B chain in Vero cells. This data suggests that eGCG may provide a starting point to refine biocompatible substances that can reduce the lethality of ricin
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