Comparative risk-based seismic assessment of 1970s vs modern tall steel moment frames

This study benchmarks the performance of older existing tall steel moment resisting frame buildings designed following historic code-prescriptive requirements (1973 Uniform Building Code) against modern design standards (2015 International Building Code). The comparison is based on seismic risk assessments of alternative designs of a 50-story archetype office building, located at a site in San Francisco, CA. The mean annual frequency collapse risk of the 1973 building is 28 times greater than the equivalent 2015 building (28 × 10^{-4} versus 1 × 10^{-4}), or approximately 13% versus 0.5% probability of collapse in 50 years. The average annual economic loss (based on cost of repair) is 65% higher for the 1973 as compared to the 2015 building (0.66% versus 0.40% of building replacement cost). The average annual downtime to re-occupancy for the 1973 building is 72% longer (8.1 vs 4.7 days) and to functional recovery is about 100% longer (10.4 vs 5.0 days). Building performance evaluations at the design basis earthquake (DBE) and the maximum considered earthquake (MCE) shaking intensities further suggest that 1970s tall steel moment frames have much higher risks of collapse under extreme ground motions and risks of damage and building closure in moderate earthquakes. Furthermore, while modern building code requirements provide acceptable seismic collapse safety, they do not necessarily ensure a level of damage control to assure a swift recovery after a damaging earthquake due to extensive downtime. A set of vulnerability functions are proposed for both archetype buildings considered in the assessment

Data and evidence challenges facing place-based policing

PURPOSE: The purpose of this paper is to use an evaluation of a micro-place-based hot-spot policing implementation to highlight the potential issues raised by data quality standards in the recording and measurement of crime data and police officer movements. DESIGN/METHODOLOGY/APPROACH: The study focusses on an area of London (UK) which used a predictive algorithm to designate micro-place patrol zones for each police shift over a two-month period. Police officer movements are measured using GPS data from officer-worn radios. Descriptive statistics regarding the crime data commonly used to evaluate this type of implementation are presented, and simple analyses are presented to examine the effects of officer patrol duration (dosage) on crime in micro-place hot-spots. FINDINGS: The results suggest that patrols of 10-20 minutes in a given police shift have a significant impact on reducing crime; however, patrols of less than about 10 minutes and more than about 20 minutes are ineffective at deterring crime. RESEARCH LIMITATIONS/IMPLICATIONS: Due to the sparseness of officer GPS data, their paths have to be interpolated which could introduce error to the estimated patrol dosages. Similarly, errors and uncertainty in recorded crime data could have substantial impact on the designation of micro-place interventions and evaluations of their effectiveness. ORIGINALITY/VALUE: This study is one of the first to use officer GPS data to estimate patrol dosage and places particular emphasis on the issue of data quality when evaluating micro-place interventions

The proteostasis boundary in misfolding diseases of membrane traffic

AbstractProtein function is regulated by the proteostasis network (PN) [Balch, W.E., Morimoto, R.I., Dillin, A. and Kelly, J.W. (2008) Adapting proteostasis for disease intervention. Science 319, 916–919], an integrated biological system that generates and protects the protein fold. The composition of the PN is regulated by signaling pathways including the unfolded protein response (UPR), the heat-shock response (HSR), the ubiquitin proteasome system (UPS) and epigenetic programs. Mismanagement of protein folding and function during membrane trafficking through the exocytic and endocytic pathways of eukaryotic cells by the PN is responsible for a wide range of diseases that include, among others, lysosomal storage diseases, myelination diseases, cystic fibrosis, systemic amyloidoses such as light chain myeloma, and neurodegenerative diseases including Alzheimer’s. Toxicity from misfolding can be cell autonomous (affect the producing cell) or cell non-autonomous (affect a non-producing cell) or both, and have either a loss-of-function or gain-of-toxic function phenotype. Herein, we review the role of the PN and its regulatory transcriptional circuitry likely to be operational in managing the protein fold and function during membrane trafficking. We emphasize the enabling principle of a ‘proteostasis boundary (PB)’ [Powers, E.T., Morimoto, R.T., Dillin, A., Kelly, J.W., and Balch, W.E. (2009) Biochemical and chemical approaches to diseases of proteostasis deficiency. Annu. Rev. Biochem. 78, 959–991]. The PB is defined by the combined effects of the kinetics and thermodynamics of folding and the kinetics of misfolding, which are linked to the variable and adjustable PN capacity found different cell types. Differences in the PN account for the versatility of protein folding and function in health, and the cellular and tissue response to mutation and environmental challenges in disease. We discuss how manipulation of the folding energetics or the PB through metabolites and pharmacological intervention provides multiple routes for restoration of biological function in trafficking disease

NASA Training Techniques for Safety Critical Operations

No abstract availabl

Transcriptome-pathology correlation identifies interplay between TDP-43 and the expression of its kinase CK1E in sporadic ALS.

Sporadic amyotrophic lateral sclerosis (sALS) is the most common form of ALS, however, the molecular mechanisms underlying cellular damage and motor neuron degeneration remain elusive. To identify molecular signatures of sALS we performed genome-wide expression profiling in laser capture microdissection-enriched surviving motor neurons (MNs) from lumbar spinal cords of sALS patients with rostral onset and caudal progression. After correcting for immunological background, we discover a highly specific gene expression signature for sALS that is associated with phosphorylated TDP-43 (pTDP-43) pathology. Transcriptome-pathology correlation identified casein kinase 1ε (CSNK1E) mRNA as tightly correlated to levels of pTDP-43 in sALS patients. Enhanced crosslinking and immunoprecipitation in human sALS patient- and healthy control-derived frontal cortex, revealed that TDP-43 binds directly to and regulates the expression of CSNK1E mRNA. Additionally, we were able to show that pTDP-43 itself binds RNA. CK1E, the protein product of CSNK1E, in turn interacts with TDP-43 and promotes cytoplasmic accumulation of pTDP-43 in human stem-cell-derived MNs. Pathological TDP-43 phosphorylation is therefore, reciprocally regulated by CK1E activity and TDP-43 RNA binding. Our framework of transcriptome-pathology correlations identifies candidate genes with relevance to novel mechanisms of neurodegeneration

Are residents of Seattle ready for ‘the Big One? An intervention study to change earthquake preparedness

Background: Community preparedness for natural hazards remains poor across cultures. In addition, evaluated intervention studies in natural hazard preparedness are scarce and contain methodological problems. This study presents results of an intervention study on earthquake preparedness conducted in Seattle, U.S.A. Methodology: This is a quasi-experimental, longitudinal, community intervention with a pretest-posttest design, focused on improving earthquake readiness at the household level. The sample included 157 adult residents of Seattle. Preparedness measures were assessed at baseline, one week after the intervention, and at three and 12 months after the intervention. This involved both of the groups in a survey and an observation of preparedness levels in their homes. The primary outcome measure was an observational tool of five preparedness items, which was implemented alongside a survey that measured psychological, social, demographic and self-reported preparedness variables. In addition, the intervention group completed a six-hour workshop on earthquake preparedness, divided over two days. The control group did not participate in the workshop. Results: The intervention group significantly improved their earthquake preparedness levels compared to baseline and to controls one week after the intervention. Nonetheless, the effect of the intervention faded at the 3-month followup, where no significant differences in earthquake preparedness were observed in the intervention group compared to baseline. In fact, preparedness appeared to increase for controls at three months compared to baseline and to one week after the intervention, and although not reaching statistical significance, it exceeded the intervention group’s preparedness levels. Anxiety and trust predicted earthquake preparedness for the control group at three months. Discussion: Despite levels of earthquake preparedness improving significantly for the intervention group right after the intervention, this effect disappeared at the 3 month follow-up, stressing the need for the field to develop measures to facilitate the maintenance of behaviour change over time. Interestingly, controls continued to improve their levels of preparedness, suggesting that the home assessments themselves might have acted as an intervention that was sufficiently powerful to trigger behaviour change in controls. Contrary to the emphasis on self-efficacy and other cognitive variables in the literature concerning natural hazard preparedness, these results suggest that emotions such as anxiety and trust might play a more important role in preparedness. Future preparedness interventions should put emotive factors centre stage in targeting preparedness. The findings of this study have implications for national and international policies on the design and delivery of community interventions to increase hazard preparedness in lay people

Kernel reconstruction for delayed neural field equations

Understanding the neural field activity for realistic living systems is a challenging task in contemporary neuroscience. Neural fields have been studied and developed theoretically and numerically with considerable success over the past four decades. However, to make effective use of such models, we need to identify their constituents in practical systems. This includes the determination of model parameters and in particular the reconstruction of the underlying effective connectivity in biological tissues. In this work, we provide an integral equation approach to the reconstruction of the neural connectivity in the case where the neural activity is governed by a delay neural field equation. As preparation, we study the solution of the direct problem based on the Banach fixed point theorem. Then we reformulate the inverse problem into a family of integral equations of the first kind. This equation will be vector valued when several neural activity trajectories are taken as input for the inverse problem. We employ spectral regularization techniques for its stable solution. A sensitivity analysis of the regularized kernel reconstruction with respect to the input signal u is carried out, investigating the Frechet differentiability of the kernel with respect to the signal. Finally, we use numerical examples to show the feasibility of the approach for kernel reconstruction, including numerical sensitivity tests, which show that the integral equation approach is a very stable and promising approach for practical computational neuroscience

Repeat doses of antibody to serum amyloid P component clear amyloid deposits in patients with systemic amyloidosis

Systemic amyloidosis is a fatal disorder caused by pathological extracellular deposits of amyloid fibrils that are always coated with the normal plasma protein, serum amyloid P component (SAP). The small-molecule drug, miridesap, [(R)-1-[6-[(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid (CPHPC)] depletes circulating SAP but leaves some SAP in amyloid deposits. This residual SAP is a specific target for dezamizumab, a fully humanized monoclonal IgG1 anti-SAP antibody that triggers immunotherapeutic clearance of amyloid. We report the safety, pharmacokinetics, and dose-response effects of up to three cycles of miridesap followed by dezamizumab in 23 adult subjects with systemic amyloidosis (ClinicalTrials.gov identifier: NCT01777243). Amyloid load was measured scintigraphically by amyloid-specific radioligand binding of 123I-labeled SAP or of 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid. Organ extracellular volume was measured by equilibrium magnetic resonance imaging and liver stiffness by transient elastography. The treatment was well tolerated with the main adverse event being self-limiting early onset rashes after higher antibody doses related to whole body amyloid load. Progressive dose-related clearance of hepatic amyloid was associated with improved liver function tests. 123I-SAP scintigraphy confirmed amyloid removal from the spleen and kidneys. No adverse cardiac events attributable to the intervention occurred in the six subjects with cardiac amyloidosis. Amyloid load reduction by miridesap treatment followed by dezamizumab has the potential to improve management and outcome in systemic amyloidosis

Substantiating a political public sphere in the Scottish press : a comparative analysis

This article uses content analysis to characterize the performance of the media in a national public sphere, by setting apart those qualities that typify internal press coverage of a political event. The article looks at the coverage of the 1999 devolved Scottish election from the day before the election until the day after. It uses a word count to measure the election material in Scottish newspapers the Herald, the Press and Journal and the Scotsman, and United Kingdom newspapers the Guardian, the Independent and The Times, and categorizes that material according to discourse type, day and page selection. The article finds a number of qualities that typify the Scottish sample in particular, and might be broadly indicative of a political public sphere in action. Firstly, and not unexpectedly, it finds that the Scottish newspapers carry significantly more election coverage. Just as tellingly, though, the article finds that the Scottish papers offer a greater proportion of advice and background information, in the form of opinion columns and feature articles. It also finds that the Scottish papers place a greater concentration of both informative and evaluative material in the period before the vote, consistent with their making a contribution to informed political action. Lastly, the article finds that the Scottish sample situates coverage nearer the front of the paper and places a greater proportion on recto pages. The article therefore argues that the Scottish papers display features that distinguish them from the UK papers, and are broadly consistent with their forming part of a deliberative public sphere, and suggests that these qualities might be explored as a means of judging future media performance