4,538 research outputs found
Time-Efficient Read/Write Register in Crash-prone Asynchronous Message-Passing Systems
The atomic register is certainly the most basic object of computing science.
Its implementation on top of an n-process asynchronous message-passing system
has received a lot of attention. It has been shown that t \textless{} n/2
(where t is the maximal number of processes that may crash) is a necessary and
sufficient requirement to build an atomic register on top of a crash-prone
asynchronous message-passing system. Considering such a context, this paper
visits the notion of a fast implementation of an atomic register, and presents
a new time-efficient asynchronous algorithm. Its time-efficiency is measured
according to two different underlying synchrony assumptions. Whatever this
assumption, a write operation always costs a round-trip delay, while a read
operation costs always a round-trip delay in favorable circumstances
(intuitively, when it is not concurrent with a write). When designing this
algorithm, the design spirit was to be as close as possible to the one of the
famous ABD algorithm (proposed by Attiya, Bar-Noy, and Dolev)
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Treatment of Porphyromonas gulae infection and downstream pathology in the aged dog by lysine-gingipain inhibitor COR388.
COR388, a small-molecule lysine-gingipain inhibitor, is currently being investigated in a Phase 2/3 clinical trial for Alzheimer's disease (AD) with exploratory endpoints in periodontal disease. Gingipains are produced by two species of bacteria, Porphyromonas gingivalis and Porphyromonas gulae, typically associated with periodontal disease and systemic infections in humans and dogs, respectively. P. gulae infection in dogs is associated with periodontal disease, which provides a physiologically relevant model to investigate the pharmacology of COR388. In the current study, aged dogs with a natural oral infection of P. gulae and periodontal disease were treated with COR388 by oral administration for up to 90 days to assess lysine-gingipain target engagement and reduction of bacterial load and downstream pathology. In a 28-day dose-response study, COR388 inhibited the lysine-gingipain target and reduced P. gulae load in saliva, buccal cells, and gingival crevicular fluid. The lowest effective dose was continued for 90 days and was efficacious in continuous reduction of bacterial load and downstream periodontal disease pathology. In a separate histology study, dog brain tissue showed evidence of P. gulae DNA and neuronal lysine-gingipain, demonstrating that P. gulae infection is systemic and spreads beyond its oral reservoir, similar to recent observations of P. gingivalis in humans. Together, the pharmacokinetics and pharmacodynamics of COR388 lysine-gingipain inhibition, along with reduction of bacterial load and periodontal disease in naturally occurring P. gulae infection in the dog, support the use of COR388 in targeting lysine-gingipain and eliminating P. gingivalis infection in humans
Glucose metabolism during liver transplantation in dogs
Arterial and hepatic venous blood levels of glucose were studied in 12 dogs during orthotopic liver transplantation peformed under ketamine anesthesia without exogenous glucose administration. During the early part of surgery, arterial blood glucose levels were stable: 161 ± 12 mg/dl (mean ± SEM) after laparotomy and 183 ± 16 mg/dl 5 min before the anhepatic stage. During the anhepatic stage, arterial blood glucose levels decreased progressively to 135 ± 9 and 88 ± 8 mg/dl, 5 min in the anhepatic stage and 5 min before reperfusion of the graft liver, respectively (P < 0.05). Reperfusion of the graft liver resulted in an increase in arterial glucose levels to 206 ± 17 and 240 ± 24 mg/dl, 5 and 30 min after reperfusion, respectively (P < 0.05). Hepatic venous blood glucose levels increased after reperfusion (405 ± 37 and 346 ± 41 mg/dl, 5 and 30 min after reperfusion, respectively) and were significantly higher than in arterial blood (P < 0.05). Arterial lasma insulin, measured in 5 animals, did not change significantly during the procedure, whereas plasma glucagon levels, stable during the preanhepatic and anhepatic stages, increased steadily after reperfusion of the graft liver, from 66.1 ± 14.2 to 108.4 ± 38.1 pg/ml (P < 0.05). This study shows that in dogs with ketamine anesthesia mild hypoglycemia occurs during the anhepatic stage of liver transplantation without exogenous glucose administration followed by hyperglycemia on reperfusion of the graft liver, possibly secondary to the release of glucose from the donor liver
A Stochastic Approach to Shortcut Bridging in Programmable Matter
In a self-organizing particle system, an abstraction of programmable matter,
simple computational elements called particles with limited memory and
communication self-organize to solve system-wide problems of movement,
coordination, and configuration. In this paper, we consider a stochastic,
distributed, local, asynchronous algorithm for "shortcut bridging", in which
particles self-assemble bridges over gaps that simultaneously balance
minimizing the length and cost of the bridge. Army ants of the genus Eciton
have been observed exhibiting a similar behavior in their foraging trails,
dynamically adjusting their bridges to satisfy an efficiency trade-off using
local interactions. Using techniques from Markov chain analysis, we rigorously
analyze our algorithm, show it achieves a near-optimal balance between the
competing factors of path length and bridge cost, and prove that it exhibits a
dependence on the angle of the gap being "shortcut" similar to that of the ant
bridges. We also present simulation results that qualitatively compare our
algorithm with the army ant bridging behavior. Our work gives a plausible
explanation of how convergence to globally optimal configurations can be
achieved via local interactions by simple organisms (e.g., ants) with some
limited computational power and access to random bits. The proposed algorithm
also demonstrates the robustness of the stochastic approach to algorithms for
programmable matter, as it is a surprisingly simple extension of our previous
stochastic algorithm for compression.Comment: Published in Proc. of DNA23: DNA Computing and Molecular Programming
- 23rd International Conference, 2017. An updated journal version will appear
in the DNA23 Special Issue of Natural Computin
Formation of regulatory modules by local sequence duplication
Turnover of regulatory sequence and function is an important part of
molecular evolution. But what are the modes of sequence evolution leading to
rapid formation and loss of regulatory sites? Here, we show that a large
fraction of neighboring transcription factor binding sites in the fly genome
have formed from a common sequence origin by local duplications. This mode of
evolution is found to produce regulatory information: duplications can seed new
sites in the neighborhood of existing sites. Duplicate seeds evolve
subsequently by point mutations, often towards binding a different factor than
their ancestral neighbor sites. These results are based on a statistical
analysis of 346 cis-regulatory modules in the Drosophila melanogaster genome,
and a comparison set of intergenic regulatory sequence in Saccharomyces
cerevisiae. In fly regulatory modules, pairs of binding sites show
significantly enhanced sequence similarity up to distances of about 50 bp. We
analyze these data in terms of an evolutionary model with two distinct modes of
site formation: (i) evolution from independent sequence origin and (ii)
divergent evolution following duplication of a common ancestor sequence. Our
results suggest that pervasive formation of binding sites by local sequence
duplications distinguishes the complex regulatory architecture of higher
eukaryotes from the simpler architecture of unicellular organisms
Long-Term Potentiation: One Kind or Many?
Do neurobiologists aim to discover natural kinds? I address this question in this chapter via a critical analysis of classification practices operative across the 43-year history of research on long-term potentiation (LTP). I argue that this 43-year history supports the idea that the structure of scientific practice surrounding LTP research has remained an obstacle to the discovery of natural kinds
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