Enhanced Partial Expansion A Goldenberg, M.; Felner, A.; Stern, R. ...
The Journal of artificial intelligence research,
01/2014, Letnik:
50
Journal Article
Recenzirano
Odprti dostop
When solving instances of problem domains that feature a large branching factor, A* may generate a large number of nodes whose cost is greater than the cost of the optimal solution. We designate such ...nodes as surplus. Generating surplus nodes and adding them to the OPEN list may dominate both time and memory of the search. A recently introduced variant of A* called Partial Expansion A* (PEA*) deals with the memory aspect of this problem. When expanding a node n, PEA* generates all of its children and puts into OPEN only the children with f = f (n). n is re-inserted in the OPEN list with the f -cost of the best discarded child. This guarantees that surplus nodes are not inserted into OPEN.
In this paper, we present a novel variant of A* called Enhanced Partial Expansion A* (EPEA*) that advances the idea of PEA* to address the time aspect. Given a priori domain- and heuristic- specific knowledge, EPEA* generates only the nodes with f = f(n). Although EPEA* is not always applicable or practical, we study several variants of EPEA*, which make it applicable to a large number of domains and heuristics. In particular, the ideas of EPEA* are applicable to IDA* and to the domains where pattern databases are traditionally used. Experimental studies show significant improvements in run-time and memory performance for several standard benchmark applications. We provide several theoretical studies to facilitate an understanding of the new algorithm.
Allelic replacement mutants were constructed within arginine deiminase (arcA1 and arcA2) to assess the function of the arginine deiminase (ADI) pathway in organic acid resistance and biofilm ...formation of Staphylococcus epidermidis 1457. A growth-dependent acidification assay (pH ∼5.0 to ∼5.2) determined that strain 1457 devoid of arginine deiminase activity (1457 ΔADI) was significantly less viable than the wild type following depletion of glucose and in the presence of arginine. However, no difference in viability was noted for individual 1457 ΔarcA1 (native) or ΔarcA2 (arginine catabolic mobile element ACME-derived) mutants, suggesting that the native and ACME-derived ADIs are compensatory in S. epidermidis. Furthermore, flow cytometry and electron paramagnetic resonance spectroscopy results suggested that organic acid stress resulted in oxidative stress that could be partially rescued by the iron chelator dipyridyl. Collectively, these results suggest that formation of hydroxyl radicals is partially responsible for cell death via organic acid stress and that ADI-derived ammonia functions to counteract this acid stress. Finally, static biofilm assays determined that viability, ammonia synthesis, and pH were reduced in strain 1457 ΔADI following 120 h of growth in comparison to strain 1457 and the arcA1 and arcA2 single mutants. It is hypothesized that ammonia synthesis via the ADI pathway is important to reduce pH stress in specific microniches that contain high concentrations of organic acids.
Assembly of extracellular filaments and matrices mediating fundamental biological processes such as morphogenesis, hearing, fertilization, and antibacterial defense is driven by a ubiquitous ...polymerization module known as zona pellucida (ZP) “domain”. Despite the conservation of this element from hydra to humans, no detailed information is available on the filamentous conformation of any ZP module protein. Here, we report a cryo‐electron microscopy study of uromodulin (UMOD)/Tamm–Horsfall protein, the most abundant protein in human urine and an archetypal ZP module‐containing molecule, in its mature homopolymeric state. UMOD forms a one‐start helix with an unprecedented 180‐degree twist between subunits enfolded by interdomain linkers that have completely reorganized as a result of propeptide dissociation. Lateral interaction between filaments in the urine generates sheets exposing a checkerboard of binding sites to capture uropathogenic bacteria, and UMOD‐based models of heteromeric vertebrate egg coat filaments identify a common sperm‐binding region at the interface between subunits.
SYNOPSIS
Urinary glycoprotein uromodulin (UMOD) forms filaments via its C‐terminal zona pellucida (ZP) module, a conserved building block of many polymeric extracellular proteins. Cryo‐EM of native human UMOD filaments and structurally‐related vertebrate egg coat material sheds light on the atomic architecture of ZP module polymers and how it may contribute to their many biological functions.
Comparison of the filament structure with that of the UMOD precursor explains how propeptide dissociation starts polymerization by triggering intermolecular interaction between ZP modules.
The linker between the ZP‐N and ZP‐C moieties of the ZP module undergoes a dramatic conformational change during polymerization.
In the filament, each UMOD subunit embraces the ZP‐C and ZP‐N domains of the neighboring molecules, giving rise to a highly stable helix made up of interlocked subunits with a twist angle of 180 degrees.
UMOD filaments can assemble into a multivalent molecular “Velcro” that facilitates the capture of uropathogenic bacteria by the N‐terminal region of the protein.
By adopting an architecture similar to the UMOD homopolymer, heteromeric egg coat filaments present sperm‐binding regions at the interface between subunits.
Insights into the architecture of uromodulin filaments involved in the capture of uropathogenic bacteria, and structurally‐related vertebrate egg coat material, suggest how a widespread extracellular polymerization module can support multiple functions.
Leonbergers are large-breed dogs believed to be predisposed to dilated cardiomyopathy, yet the normal echocardiographic measurements of these dogs are unknown. The aim of this study was to describe ...echocardiographic findings and propose breed-specific reference intervals (RIs) for Leonbergers.
A total of 42 clinically healthy dogs were involved in this study.
This study was designed as a cross-sectional study of 42 Leonberger dogs undergoing complete transthoracic echocardiographic studies at a national show. Reference intervals were determined using robust method with bootstrapping. The effects of age, sex, and body weight (BW) on linear and volumetric dimensions were evaluated by regression analysis. Intra- and interobserver variability were evaluated by coefficient of variation from 10 of the studies.
There were significant linear correlations with BW for many of the cardiac variables evaluated. However, despite the statistical significance, most regression equations had small slopes, necessitating large changes in BW for small changes in two-dimensional echocardiographic variables. As such, this study resulted in breed-specific RIs irrespective of BW. Trace mitral insufficiency (n = 18), trace aortic insufficiency (n = 15), or both (n = 1) was identified in 81% of dogs in this population. Coefficients of variation were <9% for all two-dimensional, volumetric, and motion mode measurements.
This study describes echocardiographic findings and provides RIs, which may be useful in echocardiographic evaluations of Leonbergers and may aid in early identification of heart disease within the breed.
Sea ice and snow are essential to Arctic ecosystems, playing key roles in the lives of Arctic marine mammals and the Indigenous Peoples who rely on them. Ringed seals
Pusa hispida
(‘natchiq’ in ...Iñupiaq) use snow-covered dens on sea ice for pupping, but quantitative information on denning habitat requirements is limited, and it is unknown how changes in snow depth and sea-ice extent will impact ringed seals. Here, an Indigenous Elder Advisory Council and a multidisciplinary group of scientists used knowledge co-production to quantify fine-scale ringed seal habitat selection patterns in Kotzebue Sound, Alaska (USA), during a year of unprecedentedly limited snow and sea-ice availability. Together, we conducted unoccupied aerial vehicle-based surveys during spring 2019 and related seal counts to survey date, bathymetry, and novel proxies for snow depth and surface roughness that we derived from Landsat 8 surface reflectance and validated with on-ice measurements. Generalized additive models showed that counts of seal groups (all age classes) and pups were associated with later survey dates, deeper water, and habitat with bright Landsat 8 pixel values and intermediate pixel variability, which in turn were correlated with deep snow and surface roughness. We observed shallow snow depths, early sea-ice breakup, and high seal densities consistent with the extreme lack of ice available in 2019. Indigenous Knowledge, intentionally woven with scientific data, provided novel and more nuanced understandings of snow and sea-ice conditions for seals. Our results may give a glimpse at future ringed seal habitat and selection in a warming Arctic.
The objective of the study was to evaluate the accuracy of two- and three-dimensional (2D, 3D) transthoracic echocardiography (TTE), 2D transesophageal echocardiography, and computed tomography ...angiography (CTA) compared with cardiac magnetic resonance imaging (CMR) in normal dogs and to assess repeatability of 2D and 3D TTE for the assessment of left ventricular (LV) and left atrial (LA) dimensions.
The study was performed on six healthy dogs.
Transthoracic echocardiography, transesophageal echocardiography, CTA, and CMR were performed on each dog. Right ventricular (RV) and LV volumes (in systole and diastole), ejection fraction (EF), and LA and right atrial (RA) volumes were assessed. Repeatability and intrarater and interrater measurements of variability were quantified by average coefficient of variation (CV) for 2D and 3D TTE.
No clinically relevant differences in LV volume were detected between CMR and all modalities. Importantly, 3D TTE had the lowest CV (6.45%), correlated with (rs = 0.62, p = 0.01), and had the highest overlap in distribution with CMR (OVL >80%). Left ventricular EF and LA size via CTA compared best with CMR and RV and RA volumes were best estimated by 3D TTE. Assessment of LV and LA volumes via 3D TTE had moderate repeatability (15–21%) compared with LV M-mode measurements and 2D LA-to-aortic ratio (<10%), respectively. For LV size, interrater CV for 3D TTE (19.4%) was lower than 2D TTE (23.1%).
Measurements of LV, RV, and RA volumes via 3D TTE and LA volume and LV EF assessed by CTA compared best with CMR. Three-dimensional echocardiography had lower interrater and intrarater CV compared with 2D TTE.
The scope test is widely recommended as a way to evaluate the validity of contingent valuation (CV) studies. We measured contingent values of parts and wholes for four different environmental goods ...and applied the conventional scope test. In addition, the study design allowed examination of scope relationships for individual respondents. We also used social psychological theory to expand the definition of scope to include attitudinal and behavioral scope. Looking at the individual responses showed that conventional economic scope test results, which depend on comparisons of average values, can hide important relationships that are relevant to the validity of CV studies. We showed that, as a validity test, the conventional scope test can lead to false positives and false negatives. We are led to question the efficacy and cost effectiveness of making scope tests a routine part of validity assessment in applied CV studies.
We measure fundamental‐mode Rayleigh wave group velocity dispersion from regional earthquakes and employ transdimensional Bayesian tomography to invert for azimuthally anisotropic group velocity maps ...at 10–60 s periods. Seismic azimuthal anisotropy within the crust and uppermost mantle shows fast‐axis alignment with principal northern Canadian Cordillera (NCC) tectonic structures suggesting large‐scale and coherent deformation across the crust and upper mantle. We extract group velocity dispersion curves at each grid point of the isotropic group velocity maps and invert them independently for VS as a function of depth in a probabilistic framework. At mid‐to‐lower crustal depths, our pseudo 3‐D VS model reveals an anomalously low VS structure (<3.8 km/s) across the NCC, which likely reflects elevated crustal temperatures that buoyantly support regional high elevations. Two high‐velocity regions (≥4.5 km/s) at uppermost mantle depths underpin the edges of the arcuate Mackenzie fold and thrust belt. We observe variations in the dip direction of the high‐velocity craton edge in the upper mantle, from subvertical in the northern NCC to westward in the southern NCC. We interpret a low‐velocity region (≤4.3 km/s) between the Tintina and Denali faults at uppermost mantle depths to reflect upwelling asthenosphere, which likely postdates 430 km of previously estimated Eocene lithosphere‐scale horizontal displacement along the Tintina fault. Our surface‐wave model resolves a high‐velocity region (≥4.4 km/s) dipping north‐northeast below the Wrangell volcanic field, which we interpret as a down‐going segment of the Pacific slab and may contribute to the observed volcanism in the area.
Plain Language Summary
We use regional earthquakes to extract details of the crust and uppermost mantle and develop a 3‐D seismic velocity model of northwestern Canada from the crust to the uppermost mantle. Our results show that the lower crust underlying the northern Canadian Cordillera (NCC) is anomalously slow compared to the adjacent cold and rigid craton. We suggest that the slow velocities within the NCC lower crust reflect elevated crustal temperatures that buoyantly support the high elevations of the region. At greater depths, two zones with high seismic wave velocity, located within the deeper part of the outermost layer of the Earth (i.e., lithosphere), on both ends of the Cordillera Deformation Front (CDF) controls the shape of the CDF at the surface. Moreover, a low‐velocity zone across western‐central Yukon is interpreted to reflect an upwelling of hotter mantle following the 430 km motion of a vertical (but horizontally sliding) tectonic fault (the Tintina) that penetrates into the uppermost mantle. We show changes in the geometry of the northwestern North American craton edge. We infer that a segment of the Pacific plate sinks below the Wrangell volcanic field in southeastern Alaska. Our findings have important implications regarding the tectonic evolution across the NCC.
Key Points
Anomalously slow VS within the lower crust reflects widespread high temperatures beneath the NCC that support regional high elevations
High uppermost mantle VS confirms the presence of the unexposed Mackenzie craton in northern Yukon
Upwelling of hot asthenosphere postdates 430 km of Eocene dextral motion on the Tintina fault
The Northern Canadian Cordillera (NCC) is an actively deforming orogenic belt in northwestern Canada. Geochemical and geophysical data show that the NCC is underlain by a thin and hot lithosphere, in ...contrast with the adjacent cold and thick cratonic lithosphere to the east. This juxtaposition of cold/hot and thick/thin lithosphere across a narrow transition zone has important implications for regional geodynamics. The recent deployment of USArray Transportable Array and other seismic stations across Alaska, USA, and northwestern Canada allows us to image lithosphere and upper mantle three‐dimensional seismic velocity structure at significantly improved resolution. Our model reveals a broad high‐velocity anomaly across northern Yukon and Northwest Territories, which is interpreted as buried cratonic lithosphere and which we refer to as the Mackenzie craton. Another prominent high‐velocity anomaly is imaged beneath northeastern British Columbia and is interpreted to indicate cratonic lithosphere beneath the Northern Rocky Mountains. These two mechanically strong lithospheric blocks, also suggested by regional magnetic data, are interpreted to buttress the ends of the Mackenzie Mountains fold and thrust belt, guiding intervening cordilleran mantle flow toward the Canadian Shield and controlling the arcuate geometry of the Mackenzie Mountains fold and thrust belt. Both
P and
S wave models also reveal the signature of a northward dipping, subducting Wrangell slab across the southern region of the Alaska/Yukon border. Strong
P and
S wave velocity contrasts across the Tintina Fault suggest that it is a lithosphere‐scale shear zone that extends into the upper mantle beneath the NCC and demarcates distinct regions of lithospheric mantle.
Key Points
High upper mantle seismic velocities suggest the presence of a buried craton, the Mackenzie craton, in northwestern Canada
Two strong cratonic lithospheric blocks are interpreted to act as buttresses at the edges of the Mackenzie Mountain fold and thrust belt
The Tintina Fault is a deep shear zone extending to the lithospheric mantle
Retinoblastoma is a rare childhood eye cancer caused by germline or somatic mutations in the RB1 gene. Previous studies observed elevated breast cancer risk among retinoblastoma survivors. However, ...there has been no research on breast cancer risk in relation to radiation (primarily scatter radiation from the primary treatment) and genetic susceptibility of retinoblastoma survivors.
Two groups of retinoblastoma survivors from the US and UK were selected, and breast cancer risk analysed using a case-control methodology, nesting within the respective cohorts, matching on heritability (that is to say, having bilateral retinoblastoma or being unilateral cases with at least one relative with retinoblastoma), and using exact statistical methods. There were a total of 31 cases and 77 controls.
Overall there was no significant variation of breast cancer risk with dose (P>0.5). However, there was a pronounced and significant (P=0.047) increase in the risk of breast cancer with increasing radiation dose for non-heritable retinoblastoma patients and a slight and borderline significant (P=0.072) decrease in risk of breast cancer with increasing radiation dose for heritable retinoblastoma patients, implying significant (P=0.024) heterogeneity in radiation risk between the heritable and non-heritable retinoblastoma groups; this was unaffected by the blindness status. There was no significant effect of any type of alkylating-agent chemotherapy on breast cancer risk (P>0.5).
There is significant radiation-related risk of breast cancer for non-heritable retinoblastoma survivors but no excess risk for heritable retinoblastoma survivors, and no significant risk overall. However, these results are based on very small numbers of cases; therefore, they must be interpreted with caution.
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