Comparison of Salivary pH, Buffering Capacity and Alkaline Phosphatase in Smokers and Healthy Non-Smokers : Retrospective cohort study

Objectives: Saliva contains alkaline phosphatase (ALP)—a key intracellular enzyme related to destructive processes and cellular damage—and has buffering capacity (BC) against acids due to the presence of bicarbonate and phosphate ions. Smoking may have deleterious effects on the oral environment due to pH changes which can affect ALP activity. This study aimed to evaluate the salivary pH, BC and ALP activity of male smokers and healthy non-smokers. Methods: This retrospective cohort study took place between August 2012 and December 2013. A total of 251 healthy male non-smokers and 259 male smokers from Hamadan, Iran, were selected. Unstimulated whole saliva was collected from each participant and pH and BC were determined using a pH meter. Salivary enzymes were measured by spectrophotometric assay. Results: Mean salivary pH (7.42 ± 0.48 and 7.52 ± 0.43, respectively; P = 0.018) and BC (3.41 ± 0.54 and 4.17 ± 0.71; P = 0.001) was significantly lower in smokers compared to non-smokers. Mean ALP levels were 49.58 ± 23.33 IU/L among smokers and 55.11 ± 27.85 IU/L among non-smokers (P = 0.015). Conclusion: Significantly lower pH, BC and ALP levels were observed among smokers in comparison to a healthy control group. These salivary alterations could potentially be utilised as biochemical markers for the evaluation of oral tissue function and side-effects among smokers. Further longitudinal studies are recommended to evaluate the effects of smoking on salivary components

Is SC+ILP=RC?

Sequential consistency (SC) is the simplest programming interface for shared-memory systems but imposes program order among all memory operations, possibly precluding high performance implementations. Release consistency (RC), however, enables the highest performance implementations but puts the burden on the programmer to specify which memory operations need to be atomic and in program order. This paper shows, for the first time, that SC implementations can perform as well as RC implementations if the hardware provides enough support for speculation. Both SC and RC implementations rely on reordering and overlapping memory operations for high performance. To enforce order when necessary, an RC implementation uses software guarantees, whereas an SC implementation relies on hardware speculation. Our SC implementation, called SC++, closes the performance gap because: (1) the hardware allows not just loads, as some current SC implementations do, but also stores to bypass each other speculatively to hide remote latencies, (2) the hardware provides large speculative state for not just processor, as previously proposed, but also memory to allow out-of- order memory operations, (3) the support for hardware speculation does not add excessive overheads to processor pipeline critical paths, and (4) well- behaved applications incur infrequent rollbacks of speculative execution. Using simulation, we show that SC++ achieves an RC implementation's performance in all the six applications we studie

Implicitly-multithreaded processors

This paper proposes the Implicitly-MultiThreaded (IMT) architecture to execute compiler-specified speculative threads on to a modified Simultaneous Multithreading pipeline. IMT reduces hardware complexity by relying on the compiler to select suitable thread spawning points and orchestrate inter-thread register communication. To enhance IMT's effectiveness, this paper proposes three novel microarchitectural mechanisms: (1) resource- and dependence-based fetch policy to fetch and execute suitable instructions, (2) context multiplexing to improve utilization and map as many threads to a single context as allowed by availability of resources, and (3) early thread-invocation to hide thread start-up overhead by overlapping one thread's invocation with other threads' execution. We use SPEC2K benchmarks and cycle-accurate simulation to show that an microarchitecture-optimized IMT improves performance on average by 24% and at best by 69% over an aggressive superscalar. We also compare IMT to two prior proposals, TME and DMT, for speculative threading on an SMT using hardware-extracted threads. Our best IMT design outperforms a comparable TME and DMT on average by 26% and 38% respectively

Whole blood transcriptional responses of very preterm infants during late-onset sepsis

Background Host immune responses during late-onset sepsis (LOS) in very preterm infants are poorly characterised due to a complex and dynamic pathophysiology and challenges in working with small available blood volumes. We present here an unbiased transcriptomic analysis of whole peripheral blood from very preterm infants at the time of LOS. Methods RNA-Seq was performed on peripheral blood samples (6–29 days postnatal age) taken at the time of suspected LOS from very preterm infants <30 weeks gestational age. Infants were classified based on blood culture positivity and elevated C-reactive protein concentrations as having confirmed LOS (n = 5), possible LOS (n = 4) or no LOS (n = 9). Bioinformatics and statistical analyses performed included pathway over-representation and protein-protein interaction network analyses. Plasma cytokine immunoassays were performed to validate differentially expressed cytokine pathways. Results The blood leukocyte transcriptional responses of infants with confirmed LOS differed significantly from infants without LOS (1,317 differentially expressed genes). However, infants with possible LOS could not be distinguished from infants with no LOS or confirmed LOS. Transcriptional alterations associated with LOS included genes involved in pathogen recognition (mainly TLR pathways), cytokine signalling (both pro-inflammatory and inhibitory responses), immune and haematological regulation (including cell death pathways), and metabolism (altered cholesterol biosynthesis). At the transcriptional-level cytokine responses during LOS were characterised by over-representation of IFN-α/β, IFN-γ, IL-1 and IL-6 signalling pathways and up-regulation of genes for inflammatory responses. Infants with confirmed LOS had significantly higher levels of IL-1α and IL-6 in their plasma. Conclusions Blood responses in very preterm infants with LOS are characterised by altered host immune responses that appear to reflect unbalanced immuno-metabolic homeostasis

Longer-Term Postcure Measurement of Cuspal Deformation Induced by Dimensional Changes in Dental Materials

Aim. This paper presents a simple, versatile in vitro methodology that enables indirect quantification of shrinkage and expansion stresses under clinically relevant conditions without the need for a dedicated instrument. Methods. For shrinkage effects, resulting cusp deformation of aluminum blocks with MOD type cavity, filled with novel filling compositions and commercial cements, has been measured using a bench-top micrometer and a Linear Variable Differential Transformer (LVDT, a displacement transducer) based instrument. Results. The results demonstrated the validity of the proposed simple methodology. The technique was successfully used in longer-term measurements of shrinkage and expansion stress for several dental compositions. Conclusions. In contrast to in situ techniques where a measuring instrument is dedicated to the sample and its data collection, the proposed simple methodology allows for transfer of the samples to the environment of choice for storage and conditioning. The presented technique can be reliably used to quantify stress development of curing materials under clinically relevant (oral) conditions. This enables direct examination and comparison of structural properties corresponding to the final stage of formed networks. The proposed methodology is directly applicable to the study of self-curing systems as they require mouth-type conditions (temperature and humidity) to achieve their designed kinetics and reactions

Targeting the Pseudomonas aeruginosa Virulence Factor Phospholipase C With Engineered Liposomes.

Engineered liposomes composed of the naturally occurring lipids sphingomyelin (Sm) and cholesterol (Ch) have been demonstrated to efficiently neutralize toxins secreted by Gram-positive bacteria such as Streptococcus pneumoniae and Staphylococcus aureus. Here, we hypothesized that liposomes are capable of neutralizing cytolytic virulence factors secreted by the Gram-negative pathogen Pseudomonas aeruginosa. We used the highly virulent cystic fibrosis P. aeruginosa Liverpool Epidemic Strain LESB58 and showed that sphingomyelin (Sm) and a combination of sphingomyelin with cholesterol (Ch:Sm; 66 mol/% Ch and 34 mol/% Sm) liposomes reduced lysis of human bronchial and red blood cells upon challenge with the Pseudomonas secretome. Mass spectrometry of liposome-sequestered Pseudomonas proteins identified the virulence-promoting hemolytic phospholipase C (PlcH) as having been neutralized. Pseudomonas aeruginosa supernatants incubated with liposomes demonstrated reduced PlcH activity as assessed by the p-nitrophenylphosphorylcholine (NPPC) assay. Testing the in vivo efficacy of the liposomes in a murine cutaneous abscess model revealed that Sm and Ch:Sm, as single dose treatments, attenuated abscesses by >30%, demonstrating a similar effect to that of a mutant lacking plcH in this infection model. Thus, sphingomyelin-containing liposome therapy offers an interesting approach to treat and reduce virulence of complex infections caused by P. aeruginosa and potentially other Gram-negative pathogens expressing PlcH

Exploiting choice in resizable cache design to optimize deep-submicron processor energy-delay

Cache memories account for a significant fraction of a chip's overall energy dissipation. Recent research advocates using "resizable" caches to exploit cache requirement variability in applications to reduce cache size and eliminate energy dissipation in the cache's unused sections with minimal impact on performance. Current proposals for resizable caches fundamentally vary in two design aspects: (1) cache organization, where one organization, referred to as selective-ways, varies the cache's set- associativity, while the other, referred to as selective-sets, varies the number of cache sets, and (2) resizing strategy, where one proposal statically sets the cache size prior to an application's execution, while the other allows for dynamic resizing both within and across applications. In this paper, we compare and contrast, for the first time, the proposed design choices for resizable caches, and evaluate the effectiveness of cache resizings in reducing the overall energy-delay in deep-submicron processors. In addition, we propose a hybrid selective-sets-and-ways cache organization that always offers equal or better resizing granularity than both of previously proposed organizations. We also investigate the energy savings from resizing d-cache and i-cache together to characterize the interaction between d- cache and i-cache resizing

Reunion: Complexity-effective multicore redundancy

To protect processor logic from soft errors, multicore redundant architectures execute two copies of a program on separate cores of a chip multiprocessor (CMP). Maintaining identical instruction streams is challenging because redundant cores operate independently, yet must still receive the same inputs (e.g., load values and shared-memory invalidations). Past proposals strictly replicate load values across two cores, requiring significant changes to the highly-optimized core. We make the key observation that, in the common case, both cores load identical values without special hardware. When the cores do receive different load values (e.g., due to a data race), the same mechanisms employed for soft error detection and recovery can correct the difference. This observation permits designs that relax input replication, while still providing correct redundant execution. In this paper, we present Reunion, an execution model that provides relaxed input replication and preserves the existing memory interface, coherence protocols, and consistency models. We evaluate a CMP-based implementation of the Reunion execution model with full-system, cycle-accurate simulation. We show that the performance overhead of relaxed input replication is only 5% and 6% for commercial and scientific workloads, respectively. © 2006 IEEE

Reunion: Complexity-Effective Multicore Redundancy

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