1,439 research outputs found
Solving the Uncapacitated Single Allocation p-Hub Median Problem on GPU
A parallel genetic algorithm (GA) implemented on GPU clusters is proposed to
solve the Uncapacitated Single Allocation p-Hub Median problem. The GA uses
binary and integer encoding and genetic operators adapted to this problem. Our
GA is improved by generated initial solution with hubs located at middle nodes.
The obtained experimental results are compared with the best known solutions on
all benchmarks on instances up to 1000 nodes. Furthermore, we solve our own
randomly generated instances up to 6000 nodes. Our approach outperforms most
well-known heuristics in terms of solution quality and time execution and it
allows hitherto unsolved problems to be solved
Cap-Independent Translation Promotes C. elegans Germ Cell Apoptosis through Apaf-1/CED-4 in a Caspase-Dependent Mechanism
Apoptosis is a natural process during animal development for the programmed removal of superfluous cells. During apoptosis general protein synthesis is reduced, but the synthesis of cell death proteins is enhanced. Selective translation has been attributed to modification of the protein synthesis machinery to disrupt cap-dependent mRNA translation and induce a cap-independent mechanism. We have previously shown that disruption of the balance between cap-dependent and cap-independent C. elegans eIF4G isoforms (IFG-1 p170 and p130) by RNA interference promotes apoptosis in developing oocytes. Germ cell apoptosis was accompanied by the appearance of the Apaf-1 homolog, CED-4. Here we show that IFG-1 p170 is a native substrate of the worm executioner caspase, CED-3, just as mammalian eIF4GI is cleaved by caspase-3. Loss of Bcl-2 function (ced-9ts) in worms induced p170 cleavage in vivo, coincident with extensive germ cell apoptosis. Truncation of IFG-1 occurred at a single site that separates the cap-binding and ribosome-associated domains. Site-directed mutagenesis indicated that CED-3 processes IFG-1 at a non-canonical motif, TTTD456. Coincidentally, the recognition site was located 65 amino acids downstream of the newly mapped IFG-1 p130 start site suggesting that both forms support cap-independent initiation. Genetic evidence confirmed that apoptosis induced by loss of ifg-1 p170 mRNA was caspase (ced-3) and apoptosome (ced-4/Apaf-1) dependent. These findings support a new paradigm in which modal changes in protein synthesis act as a physiological signal to initiate cell death, rather than occur merely as downstream consequences of the apoptotic event
The Analyticity of a Generalized Ruelle's Operator
In this work we propose a generalization of the concept of Ruelle operator
for one dimensional lattices used in thermodynamic formalism and ergodic
optimization, which we call generalized Ruelle operator, that generalizes both
the Ruelle operator proposed in [BCLMS] and the Perron Frobenius operator
defined in [Bowen]. We suppose the alphabet is given by a compact metric space,
and consider a general a-priori measure to define the operator. We also
consider the case where the set of symbols that can follow a given symbol of
the alphabet depends on such symbol, which is an extension of the original
concept of transition matrices from the theory of subshifts of finite type. We
prove the analyticity of the Ruelle operator and present some examples
Photorhabdus adhesion modification protein (Pam) binds extracellular polysaccharide and alters bacterial attachment.
Journal ArticleResearch Support, Non-U.S. Gov'tBACKGROUND: Photorhabdus are Gram-negative nematode-symbiotic and insect-pathogenic bacteria. The species Photorhabdus asymbiotica is able to infect humans as well as insects. We investigated the secreted proteome of a clinical isolate of P. asymbiotica at different temperatures in order to identify proteins relevant to the infection of the two different hosts. RESULTS: A comparison of the proteins secreted by a clinical isolate of P. asymbiotica at simulated insect (28 degrees C) and human (37 degrees C) temperatures led to the identification of a small and highly abundant protein, designated Pam, that is only secreted at the lower temperature. The pam gene is present in all Photorhabdus strains tested and shows a high level of conservation across the whole genus, suggesting it is both ancestral to the genus and probably important to the biology of the bacterium. The Pam protein shows limited sequence similarity to the 13.6 kDa component of a binary toxin of Bacillus thuringiensis. Nevertheless, injection or feeding of heterologously produced Pam showed no insecticidal activity to either Galleria mellonella or Manduca sexta larvae. In bacterial colonies, Pam is associated with an extracellular polysaccharide (EPS)-like matrix, and modifies the ability of wild-type cells to attach to an artificial surface. Interestingly, Surface Plasmon Resonance (SPR) binding studies revealed that the Pam protein itself has adhesive properties. Although Pam is produced throughout insect infection, genetic knockout does not affect either insect virulence or the ability of P. luminescens to form a symbiotic association with its host nematode, Heterorhabditis bacteriophora. CONCLUSIONS: We studied a highly abundant protein, Pam, which is secreted in a temperature-dependent manner in P. asymbiotica. Our findings indicate that Pam plays an important role in enhancing surface attachment in insect blood. Its association with exopolysaccharide suggests it may exert its effect through mediation of EPS properties. Despite its abundance and conservation in the genus, we find no evidence for a role of Pam in either virulence or symbiosis.BBSRCWellcome TrustEMBEK
Managing facility disruption in hub-and-spoke networks: formulations and efficient solution methods
Hub disruption result in substantially higher transportation cost and customer dissatisfaction. In this study, first a mathematical model to design hub-and-spoke networks under hub failure is presented. For a fast and inexpensive recovery, the proposed model constructs networks in which every single demand point will have a backup hub to be served from in case of disruption. The problem is formulated as a mixed integer quadratic program in a way that could be linearized without significantly increasing the number of variables. To further ease the model’ computational burden, indicator constraints are employed in the linearized model. The resulting formulation produced optimal solutions for small and some medium size instances. To tackle large problems, three efficient particle swarm optimisation-based metaheuristics which incorporate efficient solution representation, short-term memory and special crossover operator are proposed. We present the results for two scenarios relating to high and low probabilities of hub failures and provide managerial insight. The computational results, using problem instances with various sizes taken from CAB and TR datasets, confirm the effectiveness and efficiency of the proposed problem formulation and our new solution techniques
Water Use, Leaf Cooling and Carbon Assimilation Efficiency of Heat Resistant Common Beans Evaluated in Western Amazonia
In our study, we analyzed 30years of climatological data revealing the bean production risks for Western Amazonia. Climatological profiling showed high daytime and nighttime temperatures combined with high relative humidity and low vapor pressure deficit. Our understanding of the target environment allows us to select trait combinations for reaching higher yields in Amazonian acid soils. Our research was conducted using 64 bean lines with different genetic backgrounds. In high temperatures, we identified three water use efficiency typologies in beans based on detailed data analysis on gasometric exchange. Profligate water spenders and not water conservative accessions showed leaf cooling, and effective photosynthate partitioning to seeds, and these attributes were found to be related to higher photosynthetic efficiency. Thus, water spenders and not savers were recognized as heat resistant in acid soil conditions in Western Amazonia. Genotypes such as BFS 10, SEN 52, SER 323, different SEFs (SEF 73, SEF 10, SEF 40, SEF 70), SCR 56, SMR 173, and SMN 99 presented less negative effects of heat stress on yield. These genotypes could be suitable as parental lines for improving dry seed production. The improved knowledge on water-use efficiency typologies can be used for bean crop improvement efforts as well as further studies aimed at a better understanding of the intrinsic mechanisms of heat resistance in legumes
A systematic review of the evidence for single stage and two stage revision of infected knee replacement
BACKGROUND:
Periprosthetic infection about the knee is a devastating complication that may affect between 1% and 5% of knee replacement. With over 79 000 knee replacements being implanted each year in the UK, periprosthetic infection (PJI) is set to become an important burden of disease and cost to the healthcare economy. One of the important controversies in treatment of PJI is whether a single stage revision operation is superior to a two-stage procedure. This study sought to systematically evaluate the published evidence to determine which technique had lowest reinfection rates.
METHODS:
A systematic review of the literature was undertaken using the MEDLINE and EMBASE databases with the aim to identify existing studies that present the outcomes of each surgical technique. Reinfection rate was the primary outcome measure. Studies of specific subsets of patients such as resistant organisms were excluded.
RESULTS:
63 studies were identified that met the inclusion criteria. The majority of which (58) were reports of two-stage revision. Reinfection rated varied between 0% and 41% in two-stage studies, and 0% and 11% in single stage studies. No clinical trials were identified and the majority of studies were observational studies.
CONCLUSIONS:
Evidence for both one-stage and two-stage revision is largely of low quality. The evidence basis for two-stage revision is significantly larger, and further work into direct comparison between the two techniques should be undertaken as a priority
'The Brick' is not a brick: A comprehensive study of the structure and dynamics of the Central Molecular Zone cloud G0.253+0.016
In this paper we provide a comprehensive description of the internal dynamics of G0.253+0.016 (a.k.a. 'the Brick'); one of the most massive and dense molecular clouds in the Galaxy to lack signatures of widespread star formation. As a potential host to a future generation of high-mass stars, understanding largely quiescent molecular clouds like G0.253+0.016 is of critical importance. In this paper, we reanalyse Atacama Large Millimeter Array cycle 0 HNCO data at 3 mm, using two new pieces of software which we make available to the community. First, scousepy, a Python implementation of the spectral line fitting algorithm scouse. Secondly, acorns (Agglomerative Clustering for ORganising Nested Structures), a hierarchical n-dimensional clustering algorithm designed for use with discrete spectroscopic data. Together, these tools provide an unbiased measurement of the line of sight velocity dispersion in this cloud, kms, which is somewhat larger than predicted by velocity dispersion-size relations for the Central Molecular Zone (CMZ). The dispersion of centroid velocities in the plane of the sky are comparable, yielding . This isotropy may indicate that the line-of-sight extent of the cloud is approximately equivalent to that in the plane of the sky. Combining our kinematic decomposition with radiative transfer modelling we conclude that G0.253+0.016 is not a single, coherent, and centrally-condensed molecular cloud; 'the Brick' is not a \emph{brick}. Instead, G0.253+0.016 is a dynamically complex and hierarchically-structured molecular cloud whose morphology is consistent with the influence of the orbital dynamics and shear in the CMZ
Development of global temperature and pH calibrations based on bacterial 3-hydroxy fatty acids in soils
Gram-negative bacteria produce specific membrane lipids, i.e. 3-hydroxy fatty acids with 10 to 18 C atoms. They have been recently proposed as temperature and pH proxies in terrestrial settings. Nevertheless, the existing correlations between pH or temperature and indices derived from 3-OH FA distribution are based on a small soil dataset (ca. 70 samples) and only applicable regionally. The aim of this study was to investigate the applicability of 3-OH FAs as mean annual air temperature (MAAT) and pH proxies at the global level. This was achieved using an extended soil dataset of 168 topsoils distributed worldwide, covering a wide range of temperatures (5 to 30 ∘C) and pH (3 to 8). The response of 3-OH FAs to temperature and pH was compared to that of established branched glycerol dialkyl glycerol tetraether (GDGT)-based proxies (MBT'5Me/CBT). Strong linear relationships between 3-OH-FA-derived indices (RAN15, RAN17 and RIAN) and MAAT or pH could only be obtained locally for some of the individual transects. This suggests that these indices cannot be used as palaeoproxies at the global scale using simple linear regression models, in contrast with the MBT'5Me and CBT. However, strong global correlations between 3-OH FA relative abundances and MAAT or pH were shown by using other algorithms (multiple linear regression, k-NN and random forest models). The applicability of the three aforementioned models for palaeotemperature reconstruction was tested and compared with the MAAT record from a Chinese speleothem. The calibration based on the random forest model appeared to be the most robust. It generally showed similar trends with previously available records and highlighted known climatic events poorly visible when using local 3-OH FA calibrations. Altogether, these results demonstrate the potential of 3-OH FAs as palaeoproxies in terrestrial settings
β-Adrenoceptor blockade modulates fusiform gyrus activity to black versus white faces.
INTRODUCTION: The beta-adrenoceptor antagonist propranolol is known to reduce peripheral and central activity of noradrenaline. A recent study found that intervention with propranolol diminished negative implicit racial bias. MATERIALS AND METHOD: The current study used functional magnetic resonance imaging (fMRI) in order to determine the neural correlates of this effect. Healthy volunteers (N = 40) of white ethnic origin received a single oral dose (40 mg) of propranolol, in a randomised, double-blind, parallel group, placebo-controlled design, before viewing unfamiliar faces of same and other race. RESULTS AND DISCUSSION: We found significantly reduced activity in the fusiform gyrus and thalamus following propranolol to out-group faces only. Additionally, propranolol lowered the implicit attitude score, without affecting explicit prejudice measure. CONCLUSION: These findings suggest that noradrenaline pathways might modulate racial bias by acting on the processing of categorisation in the fusiform gyrus
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