1,981 research outputs found
Computer-guided discovery of epigenetics drugs: molecular modeling and identification of inhibitors of DNMT1
Regularization of image reconstruction in ultrasound computed tomography
We propose two regularizations techniques for a bent-ray (BR) tracing algorithm to reconstruct the speed of sound maps of breast tissues in an Ultrasound Computed Tomography (USCT) system. When high frequencies are employed, the use of BR is a good approximation to describe the propagation of the front of the pressure wave. The quantitative accuracy of the images reconstructed with the BR algorithm was evaluated without any kind of regularization, and with two regularization methods. The regularizations were based on some available a priori information, namely the known higher and lower values of the speed of sound expected in the breast tissues, and the maps of the internal structures obtained from the standard reflection ultrasound (US) imaging. The use of the proposed regularizations in the implemented algorithm improves the convergence and quality of the resulting images, although further improvements are still possible. These methods will help obtaining quantitative US images in a reasonable amount of time, expanding the possibilities and applications of this technique
Activity-difference maps and consensus similarity measure characterize structure-activity relationships
Towards a Context-Aware Knowledge Model for Smart Service Systems
The advancement of the Internet of things, big data, and mobile computing leads to the need for smart services that enable the context awareness and the adaptability to their changing contexts. Today, designing a smart service system is a complex task due to the lack of an adequate model support in awareness and pervasive environment. In this paper, we present a context-aware knowledge model for smart service systems that organizes the domain and context-aware knowledge into knowledge components based on the three levels of services: Services, Service system and Network of service systems. The context-aware knowledge model for smart service systems integrates all the information and knowledge related to smart services, knowledge components and context awareness that can play a key role for any framework, infrastructure, or applications deploying smart services. To demonstrate the approach, a case study about a chatbot as a smart service for customer support is presented
The role of statins in prevention and treatment of community acquired pneumonia: a systematic review and meta-analysis.
BACKGROUND: Emerging epidemiological evidence suggests that statins may reduce the risk of community-acquired pneumonia (CAP) and its complications.
PURPOSE: Performed a systematic review to address the role of statins in the prevention or treatment of CAP.
DATA SOURCE: Ovid MEDLINE, Cochrane, EMBASE, ISI Web of Science, and Scopus from inception through December 2011 were searched for randomized clinical trials, cohort and case-control studies.
STUDY SELECTION: Two authors independently reviewed studies that examined the role of statins in CAP.
DATA EXTRACTION: Data about study characteristics, adjusted effect-estimates and quality characteristics was extracted.
DATA SYNTHESIS: Eighteen studies corresponding to 21 effect-estimates (eight and 13 of which addressed the preventive and therapeutic roles of statins, respectively) were included. All studies were of good methodological quality. Random-effects meta-analyses of adjusted effect-estimates were used. Statins were associated with a lower risk of CAP, 0.84 (95% CI, 0.74-0.95), I(2) = 90.5% and a lower short-term mortality in patients with CAP, 0.68 (95% CI, 0.59-0.78), I(2) = 75.7%. Meta-regression did not identify sources of heterogeneity. A funnel plot suggested publication bias in the treatment group, which was adjusted by a novel regression method with a resultant effect-estimate of 0.85 (95% CI, 0.77-0.93). Sensitivity analyses using the rule-out approach showed that it is unlikely that the results were due to an unmeasured confounder.
CONCLUSIONS: Our meta-analysis reveals a beneficial role of statins for the risk of development and mortality associated with CAP. However, the results constitute very low quality evidence as per the GRADE framework due to observational study design, heterogeneity and publication bias
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Physical weathering of carbonate host-rock by precipitation of soluble salts in caves: A case study in El Orón-Arco Cave (Region of Murcia, SE Spain)
The dissolution of carbonate host-rock by freshwater in phreatic or vadose conditions is the most common mechanism for the formation of caves; however, circulation of saline solutions through carbonate materials and precipitation of soluble salts may also play an important role. We studied the stable isotope composition (δ18O and δ34S of sulfate, δ18O and δD of structurally-bound gypsum hydration water and 87Sr/86Sr) and salinity of fluid inclusions in gypsum speleothems found in El Orón-Arco Cave (Cartagena, SE Spain). We suggest that physical weathering of carbonate host-rock was driven by precipitation of soluble sea-salts (mostly gypsum and halite), and this process controlled the recent geomorphological evolution of the cave. The Triassic carbonate host-rock shows clear evidence for salt weathering, including gypsum/halite infillings in cracks of the bedrock, mechanical spalling of the carbonate, and detachment of rock fragments that lead to the formation cave voids and in-situ accumulations of piles of unsorted rubble. Sulfur and oxygen isotopes of gypsum sulfate (3.0‰ < δ18O < 11.6‰ and 16.7‰ < δ34S < 20.7‰) are generally lower than modern seawater sulfate and suggest contributions from a 34S-depleted source (i.e. oxidation of pyrite). The δ18O and δD of gypsum hydration water are relatively low compared to expected values for the evaporation of pure seawater to gypsum saturation, suggesting that gypsum precipitation involved a secondary calcium-sulfate source or recycling of gypsum from previous stages, along with mixing of seawater and meteoric water seepage to the cave. The 87Sr/86Sr in gypsum shows intermediate values between modern seawater and Triassic carbonate values because of interaction between the solution and the bedrock. The salinities of the speleothem-forming solutions are relatively high (13.2 ± 3.2 wt% eq. NaCl) compared to gypsum formed from evaporated brackish solutions (i.e. ~4–8 wt% eq. NaCl) and indicate dissolution of earlier evaporites before secondary gypsum precipitation. This cave-forming mechanism, which is related to saline water circulation and precipitation of evaporitic minerals, may be common in other coastal caves
Warped Radion Dark Matter
Warped scenarios offer an appealing solution to the hierarchy problem. We
consider a non-trivial deformation of the basic Randall-Sundrum framework that
has a KK-parity symmetry. This leads to a stable particle beyond the Standard
Model, that is generically expected to be the first KK-parity odd excitation of
the radion field. We consider the viability of the KK-radion as a DM candidate
in the context of thermal and non-thermal production in the early universe. In
the thermal case, the KK-radion can account for the observed DM density when
the radion decay constant is in the natural multi-TeV range. We also explore
the effects of coannihilations with the first KK excitation of the RH top, as
well as the effects of radion-Higgs mixing, which imply mixing between the
KK-radion and a KK-Higgs (both being KK-parity odd). The non-thermal scenario,
with a high radion decay constant, can also lead to a viable scenario provided
the reheat temperature and the radion decay constant take appropriate values,
although the reheat temperature should not be much higher than the TeV scale.
Direct detection is found to be feasible if the DM has a small (KK-parity odd)
Higgs admixture. Indirect detection via a photon signal from the galactic
center is an interesting possibility, while the positron and neutrino fluxes
from KK-radion annihilations are expected to be rather small. Colliders can
probe characteristic aspects of the DM sector of warped scenarios with
KK-parity, such as the degeneracy between the radion and the KK-radion (DM)
modes.Comment: 43 pages, 16 figures; added reference
Memory consolidation in the cerebellar cortex
Several forms of learning, including classical conditioning of the eyeblink, depend upon the cerebellum. In examining mechanisms of eyeblink conditioning in rabbits, reversible inactivations of the control circuitry have begun to dissociate aspects of cerebellar cortical and nuclear function in memory consolidation. It was previously shown that post-training cerebellar cortical, but not nuclear, inactivations with the GABA(A) agonist muscimol prevented consolidation but these findings left open the question as to how final memory storage was partitioned across cortical and nuclear levels. Memory consolidation might be essentially cortical and directly disturbed by actions of the muscimol, or it might be nuclear, and sensitive to the raised excitability of the nuclear neurons following the loss of cortical inhibition. To resolve this question, we simultaneously inactivated cerebellar cortical lobule HVI and the anterior interpositus nucleus of rabbits during the post-training period, so protecting the nuclei from disinhibitory effects of cortical inactivation. Consolidation was impaired by these simultaneous inactivations. Because direct application of muscimol to the nuclei alone has no impact upon consolidation, we can conclude that post-training, consolidation processes and memory storage for eyeblink conditioning have critical cerebellar cortical components. The findings are consistent with a recent model that suggests the distribution of learning-related plasticity across cortical and nuclear levels is task-dependent. There can be transfer to nuclear or brainstem levels for control of high-frequency responses but learning with lower frequency response components, such as in eyeblink conditioning, remains mainly dependent upon cortical memory storage
Elevated hemostasis markers after pneumonia increases one-year risk of all-cause and cardiovascular deaths
Background: Acceleration of chronic diseases, particularly cardiovascular disease, may increase long-term mortality after community-acquired pneumonia (CAP), but underlying mechanisms are unknown. Persistence of the prothrombotic state that occurs during an acute infection may increase risk of subsequent atherothrombosis in patients with pre-existing cardiovascular disease and increase subsequent risk of death. We hypothesized that circulating hemostasis markers activated during CAP persist at hospital discharge, when patients appear to have recovered clinically, and are associated with higher mortality, particularly due to cardiovascular causes. Methods: In a cohort of survivors of CAP hospitalization from 28 US sites, we measured D-Dimer, thrombin-antithrombin complexes [TAT], Factor IX, antithrombin, and plasminogen activator inhibitor-1 at hospital discharge, and determined 1-year all-cause and cardiovascular mortality. Results: Of 893 subjects, most did not have severe pneumonia (70.6% never developed severe sepsis) and only 13.4% required intensive care unit admission. At discharge, 88.4% of subjects had normal vital signs and appeared to have clinically recovered. D-dimer and TAT levels were elevated at discharge in 78.8% and 30.1% of all subjects, and in 51.3% and 25.3% of those without severe sepsis. Higher D-dimer and TAT levels were associated with higher risk of all-cause mortality (range of hazard ratios were 1.66-1.17, p = 0.0001 and 1.46-1.04, p = 0.001 after adjusting for demographics and comorbid illnesses) and cardiovascular mortality (p = 0.009 and 0.003 in competing risk analyses). Conclusions: Elevations of TAT and D-dimer levels are common at hospital discharge in patients who appeared to have recovered clinically from pneumonia and are associated with higher risk of subsequent deaths, particularly due to cardiovascular disease. © 2011 Yende et al
Narratives for drug design
We explore the role of narratives of complex systems in anti-cancer drug design. We set out the value of narratives relating to cancer in promoting awareness of risky behaviour and in supporting decision-making regarding treatment options. We present cancer as a dysregulated, complex system that has emergent behaviours at multiple scales, and is governed by dynamical spatio-temporal processes. We show that this system changes structure and function in response to anti-cancer drugs, and explain that these changes are sufficiently complex to impede effective drug design. We pose what narrative might offer to support the process of drug design, providing an example of work done to date that might serve as a foundation for narrating complexity. We suggest ways of using this work combined with that of others to begin to consider narrating drug design
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