Numerical Stability of Lanczos Methods

The Lanczos algorithm for matrix tridiagonalisation suffers from strong numerical instability in finite precision arithmetic when applied to evaluate matrix eigenvalues. The mechanism by which this instability arises is well documented in the literature. A recent application of the Lanczos algorithm proposed by Bai, Fahey and Golub allows quadrature evaluation of inner products of the form $\psi^\dagger g(A) \psi$. We show that this quadrature evaluation is numerically stable and explain how the numerical errors which are such a fundamental element of the finite precision Lanczos tridiagonalisation procedure are automatically and exactly compensated in the Bai, Fahey and Golub algorithm. In the process, we shed new light on the mechanism by which roundoff error corrupts the Lanczos procedureComment: 3 pages, Lattice 99 contributio

Using a motorcycle rider behaviour questionnaire (MRBQ) to investigate the predictors of motorcyclists' crash risk

In 2005, there were over 23,000 motorcyclists (including moped riders) involved in injury road traffic crashes in Great Britain and 6,142 of these riders were killed or seriously injured (Department for Transport, 2006). In order to reduce the casualty rates it is necessary to understand why motorcycle crashes happen. The present study approached this issue by investigating the role of aberrant rider behaviour, using a Motorcycle Rider Behaviour Questionnaire (MRBQ) as a framework. The aims of the study were to test the reliability and discriminant validity of the MRBQ and to examine which MRBQ behaviours relate to crash risk. Following the Driver Behaviour Questionnaire (e.g., Reason et al., 1990), which classifies driver behaviour into a system of errors ('the failure of planned actions to achieve their intended consequences') and violations ('deliberate deviations from those practices necessary to maintain the safe operation of a potentially hazardous system'), the MRBQ measured errors and violations, but with regard to motorcycling rather than car driving (see Elliott, Baughan & Sexton, 2007). The questionnaire consisted of 43 items to measure the self-reported frequency of specific riding behaviours. The questionnaire was administered to a sample of motorcyclists via a postal survey (N = 8,666). Principal components analysis revealed a 5-factor solution (TRAFFIC ERRORS, CONTROL ERRORS, SPEED VIOLATIONS, performance of STUNTS, and use of SAFETY EQUIPMENT). Generalised linear modelling showed that, while controlling for the effects of age, experience and annual mileage, TRAFFIC ERRORS were the main predictors of crash risk. For crashes in which respondents accepted some degree of blame, CONTROL ERRORS and SPEED VIOLATIONS were also significant predictors of crash risk. Implications of the findings will be discussed in relation to deciding on which countermeasures may be most effective at reducing motorcycle casualty rates

Exploring Ligand Binding to Calcitonin Gene-Related Peptide Receptors

Class B1 G protein-coupled receptors (GPCRs) are important targets for many diseases, including cancer, diabetes, and heart disease. All the approved drugs for this receptor family are peptides that mimic the endogenous activating hormones. An understanding of how agonists bind and activate class B1 GPCRs is fundamental for the development of therapeutic small molecules. We combined supervised molecular dynamics (SuMD) and classic molecular dynamics (cMD) simulations to study the binding of the calcitonin gene-related peptide (CGRP) to the CGRP receptor (CGRPR). We also evaluated the association and dissociation of the antagonist telcagepant from the extracellular domain (ECD) of CGRPR and the water network perturbation upon binding. This study, which represents the first example of dynamic docking of a class B1 GPCR peptide, delivers insights on several aspects of ligand binding to CGRPR, expanding understanding of the role of the ECD and the receptor-activity modifying protein 1 (RAMP1) on agonist selectivity

CMS Partial Releases: Model, Tools, and Applications. Online and Framework-Light Releases

The CMS Software project CMSSW embraces more than a thousand packages organized in subsystems for analysis, event display, reconstruction, simulation, detector description, data formats, framework, utilities and tools. The release integration process is highly automated by using tools developed or adopted by CMS. Packaging in rpm format is a built-in step in the software build process. For several well-defined applications it is highly desirable to have only a subset of the CMSSW full package bundle. For example, High Level Trigger algorithms that run on the Online farm, and need to be rebuilt in a special way, require no simulation, event display, or analysis packages. Physics analysis applications in Root environment require only a few core libraries and the description of CMS specific data formats. We present a model of CMS Partial Releases, used for preparation of the customized CMS software builds, including description of the tools used, the implementation, and how we deal with technical challenges, such as resolving dependencies and meeting special requirements for concrete applications in a highly automated fashion

Evaluating Diet Composition of Pronghorn in Wind Cave National Park, South Dakota

The pronghorn (Antilocapra americana) was reintroduced into Wind Cave National Park (WCNP), South Dakota, in 1914, and thus, has inhabited the Park for nearly a century. During the 1990\u27s, a decline in the population raised concern for the continued existence of pronghorn inside WCNP; an investigation into the observed decline was initiated. Primary objectives of our study were to evaluate diet composition and forage selection by pronghorn in WCNP. Microhistological analysis was conducted on 58 fecal samples collected opportunistically from pronghorn during 2002. Blue grama (Bouteloua gracilis), common juniper (Juniperus communis), and northern bedstraw (Galium boreale) were identified as major seasonal food items, representing 14.6, l 0.6, and 6.5 % of the annual diet, respectively. Annual diets of pronghorn in WCNP included 41.5% grasses, 31.1% shrubs, and 27.4% forbs. Total forage production in WCNP was 2% grass, 4% shrubs, and 23% forbs. Results indicated strong dietary selection by pronghorn for shrubs

Bitopic binding mode of an M1 muscarinic acetylcholine receptor agonist associated with adverse clinical trial outcomes

The realisation of the therapeutic potential of targeting the M1 muscarinic acetylcholine receptor (M1 mAChR) for the treatment of cognitive decline in Alzheimer's disease has prompted the discovery of M1 mAChR ligands showing efficacy in alleviating cognitive dysfunction in both rodents and humans. Among these is GSK1034702, described previously as a potent M1 receptor allosteric agonist, which showed pro-cognitive effects in rodents and improved immediate memory in a clinical nicotine withdrawal test but induced significant side-effects. Here we provide evidence using ligand binding, chemical biology and functional assays to establish that rather than the allosteric mechanism claimed, GSK1034702 interacts in a bitopic manner at the M1 mAChR such that it can concomitantly span both the orthosteric and an allosteric binding site. The bitopic nature of GSK1034702 together with the intrinsic agonist activity and a lack of muscarinic receptor subtype selectivity reported here, all likely contribute to the adverse effects of this molecule in clinical trials. We conclude that these properties, whilst imparting beneficial effects on learning and memory, are undesirable in a clinical candidate due to the likelihood of adverse side effects. Rather, our data supports the notion that "pure" positive allosteric modulators showing selectivity for the M1 mAChR with low levels of intrinsic activity would be preferable to provide clinical efficacy with low adverse responses

Carbon concentration of standing and downed woody detritus: Effects of tree taxa, decay class, position, and tissue type

The degree to which carbon concentration (CC) of woody detritus varies by tree taxa, stage of decay, tissue type (i.e., bark versus wood), and vertical orientation was examined in samples of 60 tree species from the Northern Hemisphere. The mean CC of 257 study samples was 49.3% with a range of 43.4– 56.8%. Angiosperms had a significantly lower CC than gymnosperms, with means of 47.8% and 50.6%, respectively. For whole-stems (i.e., wood and bark), the CC of gymnosperms significantly increased from 49.3% to 53.5% with decomposition, while angiosperms had no significant change. The CC of bark was higher than wood across all stages of decay by an average of ~1.0%. A similar magnitude of difference was found for standing versus downed dead wood in the later stages of decay, with the former having a higher CC than the latter. Differences between angiosperms and gymnosperms are hypothesized to be associated with initial lignin concentrations as well as subsequent decomposition by white- versus brown-rot fungal functional groups. The higher abundance of brown-rots in decomposing gymnosperms may lead to an increase in lignin concentrations, a compound that has higher CC than cellulose. As a result of these findings, uncertainties associated with forest carbon inventories may be reduced by using detrital CC specific to general taxa (angiosperms versus gymnosperms) and stage of decay rather than a single assumed value of 50% as commonly practiced.Keywords: Carbon, Gymnosperm, Bark, Coarse woody debris, Angiosperm, Woo

Extracting random numbers from quantum tunnelling through a single diode

Random number generation is crucial in many aspects of everyday life, as online security and privacy depend ultimately on the quality of random numbers. Many current implementations are based on pseudo-random number generators, but information security requires true random numbers for sensitive applications like key generation in banking, defence or even social media. True random number generators are systems whose outputs cannot be determined, even if their internal structure and response history are known. Sources of quantum noise are thus ideal for this application due to their intrinsic uncertainty. In this work, we propose using resonant tunnelling diodes as practical true random number generators based on a quantum mechanical effect. The output of the proposed devices can be directly used as a random stream of bits or can be further distilled using randomness extraction algorithms, depending on the application

Atomic-scale authentication with resonant tunneling diodes

The room temperature electronic characteristics of resonant tunneling diodes (RTDs) containing AlAs/InGaAs quantum wells are studied. Differences in the peak current and voltages, associated with device-to-device variations in the structure and width of the quantum well are analyzed. A method to use these differences between devices is introduced and shown to uniquely identify each of the individual devices under test. This investigation shows that quantum confinement in RTDs allows them to operate as physical unclonable functions

Systemic Racism and Health Disparities: A Statement from Editors of Family Medicine Journals

The year 2020 has been marked by historic protests across the United States and the globe sparked by the deaths of George Floyd, Ahmaud Arbery, Breonna Taylor, and so many other Black people. The protests heightened awareness of racism as a public health crisis and triggered an antiracism movement. The editors of several North American family medicine publications have come together to address this call to action and share resources on racism across our readerships.http://deepblue.lib.umich.edu/bitstream/2027.42/163331/1/Final Statement on Systemic Racism- with acknowledgements.pdf-1Description of Final Statement on Systemic Racism- with acknowledgements.pdf : Main ArticleSEL