An Improved Approximate Consensus Algorithm in the Presence of Mobile Faults

This paper explores the problem of reaching approximate consensus in synchronous point-to-point networks, where each pair of nodes is able to communicate with each other directly and reliably. We consider the mobile Byzantine fault model proposed by Garay '94 -- in the model, an omniscient adversary can corrupt up to $f$ nodes in each round, and at the beginning of each round, faults may "move" in the system (i.e., different sets of nodes may become faulty in different rounds). Recent work by Bonomi et al. '16 proposed a simple iterative approximate consensus algorithm which requires at least $4f+1$ nodes. This paper proposes a novel technique of using "confession" (a mechanism to allow others to ignore past behavior) and a variant of reliable broadcast to improve the fault-tolerance level. In particular, we present an approximate consensus algorithm that requires only $\lceil 7f/2\rceil + 1$ nodes, an $\lfloor f/2 \rfloor$ improvement over the state-of-the-art algorithms. Moreover, we also show that the proposed algorithm is optimal within a family of round-based algorithms

Extrafine beclomethasone/formoterol in severe COPD patients with history of exacerbations

The FORWARD study is a randomised, double-blind trial that compares the efficacy and safety of 48 weeks treatment with extrafine beclomethasone dipropionate/formoterol fumarate (BDP/FOR), 100/6 μg pMDI, 2 inhalations BID, vs. FOR 12 μg pMDI, 1 inhalation BID, in severe COPD patients with a history of exacerbations. Co-primary endpoints were exacerbation rate over 48 weeks and pre-dose morning FEV1 at 12 weeks. The ITT population included 1186 patients (69% males, mean age 64 years) with severe airflow limitation (mean post-bronchodilator FEV1 42% predicted). Salbutamol as rescue therapy, theophylline and tiotropium (if stable regimen prior to screening) were allowed. Compared to FOR, BDP/FOR: (1) reduced the exacerbation rate (rate ratio: 0.72 [95% confidence interval 0.62–0.84], p < 0.001); (2) improved pre-dose morning FEV1 (mean difference: 0.069 L [0.043–0.095] p < 0.001); (3) prolonged the time to first exacerbation; (4) improved the SGRQ total score. The percentage of patients with adverse events was similar (52.1% with BDP/FOR and 49.2% with FOR). Pneumonia incidence was low, slightly higher with BDP/FOR (3.8%) than with FOR (1.8%). No difference for laboratory values, ECG or vital signs. Extrafine BDP/FOR significantly reduces the exacerbation rate and improves lung function of patients with severe COPD and history of exacerbations as compared to FOR alone

Performance of the 2007 WHO Algorithm to diagnose Smear-negative Pulmonary Tuberculosis in a HIV prevalent setting

The 2007 WHO algorithm for diagnosis of smear-negative pulmonary tuberculosis (PTB) including Mycobacterium tuberculosis (MTB) culture was evaluated in a HIV prevalent area of Kenya

Single-molecule visualization reveals the damage search mechanism for the human NER protein XPC-RAD23B

DNA repair is critical for maintaining genomic integrity. Finding DNA lesions initiates the entire repair process. In human nucleotide excision repair (NER), XPC-RAD23B recognizes DNA lesions and recruits downstream factors. Although previous studies revealed the molecular features of damage identification by the yeast orthologs Rad4-Rad23, the dynamic mechanisms by which human XPC-RAD23B recognizes DNA defects have remained elusive. Here, we directly visualized the motion of XPC-RAD23B on undamaged and lesion-containing DNA using high-throughput single-molecule imaging. We observed three types of one-dimensional motion of XPC-RAD23B along DNA: diffusive, immobile and constrained. We found that consecutive AT-tracks led to increase in proteins with constrained motion. The diffusion coefficient dramatically increased according to ionic strength, suggesting that XPC-RAD23B diffuses along DNA via hopping, allowing XPC-RAD23B to bypass protein obstacles during the search for DNA damage. We also examined how XPC-RAD23B identifies cyclobutane pyrimidine dimers (CPDs) during diffusion. XPC-RAD23B makes futile attempts to bind to CPDs, consistent with low CPD recognition efficiency. Moreover, XPC-RAD23B binds CPDs in biphasic states, stable for lesion recognition and transient for lesion interrogation. Taken together, our results provide new insight into how XPC-RAD23B searches for DNA lesions in billions of base pairs in human genome

Beyond the standard seesaw: neutrino masses from Kahler operators and broken supersymmetry

We investigate supersymmetric scenarios in which neutrino masses are generated by effective d=6 operators in the Kahler potential, rather than by the standard d=5 superpotential operator. First, we discuss some general features of such effective operators, also including SUSY-breaking insertions, and compute the relevant renormalization group equations. Contributions to neutrino masses arise at low energy both at the tree level and through finite threshold corrections. In the second part we present simple explicit realizations in which those Kahler operators arise by integrating out heavy SU(2)_W triplets, as in the type II seesaw. Distinct scenarios emerge, depending on the mechanism and the scale of SUSY-breaking mediation. In particular, we propose an appealing and economical picture in which the heavy seesaw mediators are also messengers of SUSY breaking. In this case, strong correlations exist among neutrino parameters, sparticle and Higgs masses, as well as lepton flavour violating processes. Hence, this scenario can be tested at high-energy colliders, such as the LHC, and at lower energy experiments that measure neutrino parameters or search for rare lepton decays.Comment: LaTeX, 34 pages; some corrections in Section

Taxonomic Chauvinism Revisited: Insight from Parental Care Research

Parental care (any non-genetic contribution by a parent that appears likely to increase the fitness of its offspring) is a widespread trait exhibited by a broad range of animal taxa. In addition to influencing the fitness of parent(s) and offspring, parental care may be inextricably involved in other evolutionary processes, such as sexual selection and the evolution of endothermy. Yet, recent work has demonstrated that bias related to taxonomy is prevalent across many biological disciplines, and research in parental care may be similarly burdened. Thus, I used parental care articles published in six leading journals of fundamental behavioral sciences (Animal Behaviour, Behavioral Ecology, Behavioral Ecology and Sociobiology, Ethology, Hormones and Behavior, and Physiology & Behavior) from 2001–2010 (n = 712) to examine the year-to-year dynamics of two types of bias related to taxonomy across animals: (1) taxonomic bias, which exists when research output is not proportional to the frequency of organisms in nature, and (2) taxonomic citation bias, which is a proxy for the breadth of a given article—specifically, the proportion of articles cited that refer solely to the studied taxon. I demonstrate that research on birds likely represents a disproportionate amount of parental care research and, thus, exhibits taxonomic bias. Parental care research on birds and mammals also refers to a relatively narrow range of taxonomic groups when discussing its context and, thus, exhibits taxonomic citation bias. Further, the levels of taxonomic bias and taxonomic citation bias have not declined over the past decade despite cautionary messages about similar bias in related disciplines— in fact, taxonomic bias may have increased. As in Bonnet et al. (2002), my results should not be interpreted as evidence of an ‘ornithological Mafia’ conspiring to suppress other taxonomic groups. Rather, I generate several rational hypotheses to determine why bias persists and to guide future work

WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics

Prostate cancer cells with stem cell characteristics were identified in human prostate cancer cell lines by their ability to form from single cells self-renewing prostaspheres in non-adherent cultures. Prostaspheres exhibited heterogeneous expression of proliferation, differentiation and stem cell-associated makers CD44, ABCG2 and CD133. Treatment with WNT inhibitors reduced both prostasphere size and self-renewal. In contrast, addition of Wnt3a caused increased prostasphere size and self-renewal, which was associated with a significant increase in nuclear Β-catenin, keratin 18, CD133 and CD44 expression. As a high proportion of LNCaP and C4-2B cancer cells express androgen receptor we determined the effect of the androgen receptor antagonist bicalutamide. Androgen receptor inhibition reduced prostasphere size and expression of PSA, but did not inhibit prostasphere formation. These effects are consistent with the androgen-independent self-renewal of cells with stem cell characteristics and the androgen-dependent proliferation of transit amplifying cells. As the canonical WNT signaling effector Β-catenin can also associate with the androgen receptor, we propose a model for tumour propagation involving a balance between WNT and androgen receptor activity. That would affect the self-renewal of a cancer cell with stem cell characteristics and drive transit amplifying cell proliferation and differentiation. In conclusion, we provide evidence that WNT activity regulates the self-renewal of prostate cancer cells with stem cell characteristics independently of androgen receptor activity. Inhibition of WNT signaling therefore has the potential to reduce the self-renewal of prostate cancer cells with stem cell characteristics and improve the therapeutic outcome.Peer reviewe

Insufficient Rest or Sleep and Its Relation to Cardiovascular Disease, Diabetes and Obesity in a National, Multiethnic Sample

BACKGROUND: A new question on insufficient rest/sleep was included in the 2008 Behavioral Risk Factor Surveillance System (BRFSS) for the 50 states, District of Columbia, and three US territories. No previous study, however, has examined perceived insufficient rest/sleep in relation to cardiovascular disease (CVD) or diabetes mellitus. We examined the association between self-reported insufficient rest/sleep and CVD, diabetes, and obesity in a contemporary sample of US adults. METHODS: Multiethnic, nationally representative, cross-sectional survey (2008 BRFSS) participants were >20 years of age (n=372, 144, 50% women). Self-reported insufficient rest/sleep in the previous month was categorized into four groups: zero, 1-13, 14-29, and 30 days. There were five outcomes: 1) any CVD, 2) coronary heart disease (CHD), 3) stroke, 4) diabetes mellitus, and 5) obesity (body mass index≥30 kg/m2). We employed multivariable logistic regression to calculate odds ratio (OR), (95% confidence interval (CI), of increasing categories of insufficient rest/sleep, taking zero days of insufficient rest/sleep as the referent category. PRINCIPAL FINDINGS: Insufficient rest/sleep was found to be associated with 1) any CVD, 2) CHD, 3) stroke, 4) diabetes mellitus, and 5) obesity, in separate analyses. Compared to those reporting zero days of insufficient sleep (referent), the OR (95% CI) associated with all 30 days of insufficient sleep was 1.67 (1.55-1.79) for any cardiovascular disease, 1.69(1.56-1.83) for CHD, 1.51(1.36-1.68) for stroke, 1.31(1.21-1.41) for diabetes, and 1.51 (1.43-1.59) for obesity. CONCLUSIONS: In a multiethnic sample of US adults, perceived insufficient rest/sleep was found to be independently associated with CHD, stroke, diabetes mellitus and obesity

The PEX7-Mediated Peroxisomal Import System Is Required for Fungal Development and Pathogenicity in Magnaporthe oryzae

In eukaryotes, microbodies called peroxisomes play important roles in cellular activities during the life cycle. Previous studies indicate that peroxisomal functions are important for plant infection in many phytopathogenic fungi, but detailed relationships between fungal pathogenicity and peroxisomal function still remain unclear. Here we report the importance of peroxisomal protein import through PTS2 (Peroxisomal Targeting Signal 2) in fungal development and pathogenicity of Magnaporthe oryzae. Using an Agrobacterium tumefaciens-mediated transformation library, a pathogenicity-defective mutant was isolated from M. oryzae and identified as a T-DNA insert in the PTS2 receptor gene, MoPEX7. Gene disruption of MoPEX7 abolished peroxisomal localization of a thiolase (MoTHL1) containing PTS2, supporting its role in the peroxisomal protein import machinery. ΔMopex7 showed significantly reduced mycelial growth on media containing short-chain fatty acids as a sole carbon source. ΔMopex7 produced fewer conidiophores and conidia, but conidial germination was normal. Conidia of ΔMopex7 were able to develop appressoria, but failed to cause disease in plant cells, except after wound inoculation. Appressoria formed by ΔMopex7 showed a defect in turgor generation due to a delay in lipid degradation and increased cell wall porosity during maturation. Taken together, our results suggest that the MoPEX7-mediated peroxisomal matrix protein import system is required for fungal development and pathogenicity M. oryzae