Fast self-stabilizing byzantine tolerant digital clock synchronization

Consider a distributed network in which up to a third of the nodes may be Byzantine, and in which the non-faulty nodes may be subject to transient faults that alter their memory in an arbitrary fashion. Within the context of this model, we are interested in the digital clock synchronization problem; which consists of agreeing on bounded integer counters, and increasing these counters regularly. It has been postulated in the past that synchronization cannot be solved in a Byzantine tolerant and self-stabilizing manner. The first solution to this problem had an expected exponential convergence time. Later, a deterministic solution was published with linear convergence time, which is optimal for deterministic solutions. In the current paper we achieve an expected constant convergence time. We thus obtain the optimal probabilistic solution, both in terms of convergence time and in terms of resilience to Byzantine adversaries

Psychometric properties of the Hebrew Modified Dental Anxiety Scale in adult Israeli population

Dental anxiety results in the neglect of oral hygiene and poor oral health, requiring an accurate screening tool for dental practitioners to evaluate dental anxiety. The Modified Dental Anxiety Scale (MDAS) is frequently used cross-culturally. The present study aimed to assess the reliability and validity of the Hebrew version of the MDSA. A total of 553 (mean age 35.87 years, SD = 13.14) Israeli participants were recruited through means of social media, mailing lists, and forums. The sample was randomly divided into two population sets. Dental anxiety was evaluated using the Hebrew version of the MDAS. The psychometric evaluation consisted of exploratory factor analysis (study 1, n = 274) and confirmatory factor analysis (study 2, n = 279). Cronbach’s alpha coefficient was used to assess internal consistency. Results showed high internal consistency (0.93) for the Hebrew version of the MDAS. Confirmatory factor analysis showed a single factor solution. Findings demonstrated 13.4% of Israeli participants with dental anxiety. Younger participants, females, participants with lower education, lower income, and more religious participants reported higher dental anxiety. In conclusion, the Hebrew version of the MDAS demonstrated high reliability and validity. It is recommended to use the Hebrew version of the MDAS to evaluate dental anxiety in Israeli dental settings.Publisher PDFPeer reviewe

Dose Effect of Whey Protein on Gut Hormone Responses in Pre-Diabetics and Type 2 Diabetics

GLP-1 and GIP have been shown to increase following a 50 g dose of whey protein prior to a high glycemic load in type 2 diabetics. However, this increase is reduced in diabetics compared to healthy individuals. Pancreatic polypeptide (PP) and peptide tyrosine tyrosine (PYY) also increase, while ghrelin decreases after the consumption of whey protein; however, it is not known if a similar hormone response occurs with a lower dose of whey protein prior to a glycemic load or if there is a dose effect. Our hypothesis was that 20 g and 30 g of whey protein would increase GLP-1, GIP, PP, and PYY and decrease ghrelin in a dose dependent manner. PURPOSE: The purpose of this study was to examine the effect of two different doses of whey protein ingested 30 min prior to a 50 g OGTT on gut hormone and incretin response. METHODS: Nine diabetic and pre-diabetic participants (n=9, mean ± SD; age: 64.3 + 8.1 yrs.; BMI: 29.4 + 6.0 kg/m2; HbA1c: 6.4 + 0.6%) completed three trials. The randomly assigned trials consisted of: ingestion of 250ml of water (CON); 250 ml of water + 20 g whey (20g); 250ml of water + 30 g whey (30g), prior to completing a 50 g OGTT. Blood was collected at -30, 0, 15, 30, 60, 90, 120, and 150 min for the measurement of GIP, GLP-1, ghrelin, PP, and PYY. The whey protein was administered immediately following the -30 min and the 50 g OGTT began immediately after the 0 min blood draw. Metabolites were measured using multiplex fluorescent detection. One-way repeated measure ANOVA was used for statistical analysis for each dependent variable (P \u3c 0.05). RESULTS: 20g and 30g of whey protein significantly increased incremental area under the curve (AUC) of GIP 32% and 38% compared to CON. 30g significantly decreased ghrelin AUC -13.9% and -20% compared to 20g and CON. 30g significantly increased PP AUC 28% compared to CON only. There were no differences in ghrelin and PP AUC between 20g and CON. There were no significant differences for GLP-1 and PYY between all trials. CONCLUSION: 30 g of whey protein prior to a glucose challenge increased secretion of GIP and PP and decreased ghrelin in type 2 and pre-diabetics. There seems to be a dose effect relationship between whey, ghrelin, and PP. 30 g of whey preload may induce insulinotropic and satiety effects from GIP, PP, and ghrelin responses in type 2 and pre-diabetics

The Dose Effect of Whey Protein on Insulin Responses in Pre-Diabetics and Type 2 Diabetics

People with pre-diabetes and type 2 diabetes have shown an increase in insulin secretion after ingesting 55 g of whey protein coupled with a glycemic challenge. However, the effect of lower amounts of whey protein on insulin responses remains unclear. Our hypothesis was that both 20 g and 30 g of whey consumption prior to an oral glucose tolerance test (OGTT) would produce an increase in insulin secretion, with 30 g producing the greatest increase compared to a control. PURPOSE: The purpose of this study was to examine the effect of two different doses of whey protein ingested 30 min prior to a 50 g OGTT on glucose, insulin, C-peptide, and glucagon responses. METHODS: Diabetic or pre-diabetic participants (n=9, mean ± SD; age: 64.3 + 8.1 yrs; BMI: 29.4 + 6.0 kg/m2; body fat percentage: 42.5 + 7.8 %; fasting plasma glucose: 6.9 + 1.2 mmol/l; HbA1c: 6.4 + 0.6 %) completed three trials. The randomly assigned trials consisted of: 250 ml of water (CON), 250 ml of water + 20 g whey (20g), and 250 ml of water + 30 g whey (30g), followed by an OGTT. Blood was collected at -30, 0, 15, 30, 60, 90, 120, and 150 min for the measurement of glucose, insulin, C-peptide, and glucagon. The whey protein mixture was administered immediately following the -30 min blood draw, and the 50 g OGTT began immediately following the 0 min blood draw. Glucose was analyzed using a YSI 2900D glucose analyzer and insulin, C-peptide, and glucagon were measured via multiplex fluorescent detection (MagPix). A one-way repeated measures ANOVA (pRESULTS: Incremental area under the curve (AUC) for glucose presented no difference between the 3 trials. Insulin AUC was significantly increased from CON to 20g (p=0.004, 36.3%), CON to 30g (p=0.002, 61.7%), and 20g to 30g (p=0.030, 18.6%). C-peptide and glucagon AUC significantly increased from CON to 20g (p=0.018, 20.6%; p=0.046, 33.1%) and CON to 30g (p=0.001, 30.1%; p=0.017, 33.7%). CONCLUSION: Whey protein elicited a dose response on plasma insulin, increasing concentrations from CON to 20g, and 20g to 30g, however plasma glucose was unaffected. 20g and 30g displayed similar responses for glucagon. Neither 20 g nor 30 g of whey protein may be adequate to provide glycemic improvement in the disease management of type 2 or pre-diabetes

Characterization of Pyrrolidinyl-hexahydro-pyranopiperazines as a Novel Kappa Opioid Receptor Agonist Scaffold

The kappa agonist structure–activity relationship around the novel, pyrrolidinyl substituted pyranopiperazine scaffold was developed. More specifically, the dichloroPhenylAcetamide-Pyrrolidinyl-PyranoPiperazine (PAPPP) core A was the focus of our work. The modulation of kappa receptor potency/G-protein activation and arrestin recruitment with respect to changes of the piperazine R group in A was demonstrated. Reduced β2-arrestin recruitment and differential G-protein bias were observed for select analogues. To better understand the subtlety in receptor signaling, analogues were profiled as the resolved enantiomers. To determine in vivo target engagement, a subset of compounds was tested in mice for stimulation of serum prolactin, a neuroendocrine biomarker of KOR-agonist effects. Additional in vivo characterization included measurement of potential unwanted effects of kappa receptor activation such as sedation. These studies demonstrate a novel kappa receptor agonist scaffold with potential for G-protein signaling bias to probe in vivo pharmacology

High Intensity Interval Exercise Does Not Influence Overnight GH Secretion in Overweight Sedentary Young Women

Exercise and sleep are the two major factors that influence growth hormone (GH) secretion and it has been well established that there is a strong positive relationship between exercise intensity and GH release. This dose-dependent response may also be correlated with the lactate response to exercise, with steady-state exercise intensities above the lactate threshold eliciting a greater GH pulse. It has yet to be determined, however, if high-intensity interval exercise (HIE) can influence overnight pulsatile GH secretion, which accounts for the majority of daily GH release. PURPOSE: To determine if HIE significantly increased overnight GH secretion compared to continuous moderate-intensity exercise (MOD), or no exercise (CON) in young women. METHODS: Five young, sedentary women (mean ± SD age: 22.6 ± 1.3 y; BMI: 27.4 ± 3.1 kg/m2; body fat: 39.2 ± 1.7 %; VO2max: 29.4 ± 5.7 mL/kg/min) were studied on three different occasions during the follicular phase of their menstrual cycle (CON: no exercise; MOD: 30-min of continuous cycling at 50% of peak power determined from the VO2max test; and HIE: 4 30-s “all-out” sprints at a resistance equal to 6.5% body mass with 4.5-min recovery. Each trial was randomly assigned and separated by a minimum of one month. For each visit, participants reported to the lab at 1700h, exercised from 1730h – 1800h, and remained in the lab until 0700h the following morning. The overnight GH secretory profile of each trial was determined from 10-min sampling of venous blood from 1730h – 0600h (12.5 h) using deconvolution analysis. RESULTS: Mean power output during MOD was 80.6 ± 6.3 W (68.2 ± 9.7 %VO2max). Estimated exercising energy expenditure for MOD (145.1 ± 11.2 kcal) was significantly lower than HIE (204.5 ± 15.5 kcal, P = 0.002). Peak lactate was significantly higher during MOD (4.7 ± 0.9 mmol/L) compared to CON (0.9 ± 0.2 mmol/L, P = 0.002) and was highest during HIE (11.2 ± 2.1 mmol/L) compared to MOD (P \u3c 0.001) and CON (P \u3c 0.001). Calculated GH AUC (0 – 120 min) was significantly greater in HIE (1018.2 ± 576.1 ng· min/mL) than CON (181.7 ± 138.9 ng· min/mL, P = 0.009), but not MOD (544.7 ± 160.7 ng· min/mL). Overnight GH production rate (ng/mL/min) determined by deconvolution analysis was not significantly different between CON (1040.3 ± 242.0), MOD (1429.2 ± 206.0), and HIE (1831.2 ± 873.8, P = 0.107). Other GH secretory variables: basal GH concentration (ng/mL), number of GH peaks, GH pulse amplitude and mass, and interpulse interval were not different between the three trials. CONCLUSION: For these untrained, overweight sedentary young women, a single bout of exercise was insufficient to significantly affect overnight pulsatile GH secretion. Adiposity is a negative determinant of GH secretion, and the GH response to exercise in these women was extremely variable. Aerobic fitness, prior training, as well as several metabolic factors associated with obesity (e.g., increased insulin and circulating free fatty acids) can also influence GH secretion and should be taken into account as potential mediators of the GH response to exercise

Single-laser 32.5 Tbit/s Nyquist WDM transmission

We demonstrate 32.5 Tbit/s 16QAM Nyquist WDM transmission over a total length of 227 km of SMF-28 without optical dispersion compensation. A number of 325 optical carriers are derived from a single laser and encoded with dual-polarization 16QAM data using sinc-shaped Nyquist pulses. As we use no guard bands, the carriers have a spacing of 12.5 GHz equal to the Nyquist bandwidth of the data. We achieve a high net spectral efficiency of 6.4 bit/s/Hz using a software-defined transmitter which generates the electrical modulator drive signals in real-time.Comment: (c) 2012 Optical Society of America. One print or electronic copy may be made for personal use only. Systematic reproduction and distribution, duplication of any material in this paper for a fee or for commercial purposes, or modifications of the content of this paper are prohibite

PI3Kγ is a molecular switch that controls immune suppression

Macrophages play critical, but opposite, roles in acute and chronic inflammation and cancer1,2,3,4,5. In response to pathogens or injury, inflammatory macrophages express cytokines that stimulate cytotoxic T cells, whereas macrophages in neoplastic and parasitic diseases express anti-inflammatory cytokines that induce immune suppression and may promote resistance to T cell checkpoint inhibitors1,2,3,4,5,6,7. Here we show that macrophage PI 3-kinase γ controls a critical switch between immune stimulation and suppression during inflammation and cancer. PI3Kγ signalling through Akt and mTor inhibits NFκB activation while stimulating C/EBPβ activation, thereby inducing a transcriptional program that promotes immune suppression during inflammation and tumour growth. By contrast, selective inactivation of macrophage PI3Kγ stimulates and prolongs NFκB activation and inhibits C/EBPβ activation, thus promoting an immunostimulatory transcriptional program that restores CD8+ T cell activation and cytotoxicity. PI3Kγ synergizes with checkpoint inhibitor therapy to promote tumour regression and increased survival in mouse models of cancer. In addition, PI3Kγ-directed, anti-inflammatory gene expression can predict survival probability in cancer patients. Our work thus demonstrates that therapeutic targeting of intracellular signalling pathways that regulate the switch between macrophage polarization states can control immune suppression in cancer and other disorders