Partial Covering Arrays: Algorithms and Asymptotics

A covering array $\mathsf{CA}(N;t,k,v)$ is an $N\times k$ array with entries in $\{1, 2, \ldots , v\}$, for which every $N\times t$ subarray contains each $t$-tuple of $\{1, 2, \ldots , v\}^t$ among its rows. Covering arrays find application in interaction testing, including software and hardware testing, advanced materials development, and biological systems. A central question is to determine or bound $\mathsf{CAN}(t,k,v)$, the minimum number $N$ of rows of a $\mathsf{CA}(N;t,k,v)$. The well known bound $\mathsf{CAN}(t,k,v)=O((t-1)v^t\log k)$ is not too far from being asymptotically optimal. Sensible relaxations of the covering requirement arise when (1) the set $\{1, 2, \ldots , v\}^t$ need only be contained among the rows of at least $(1-\epsilon)\binom{k}{t}$ of the $N\times t$ subarrays and (2) the rows of every $N\times t$ subarray need only contain a (large) subset of $\{1, 2, \ldots , v\}^t$. In this paper, using probabilistic methods, significant improvements on the covering array upper bound are established for both relaxations, and for the conjunction of the two. In each case, a randomized algorithm constructs such arrays in expected polynomial time

Sixteen-Week physical activity intervention in subjects with increased cardiometabolic risk shifts innate immune function towards a less pro-inflammatory state.

Background Low-grade inflammation, largely mediated by monocyte-derived macrophages, contributes to atherosclerosis. Sedentary behavior is associated with atherosclerosis and cardiovascular diseases (CVD). We examined whether reducing sedentary behavior and improving walking time improves monocyte inflammatory phenotype in subjects with increased cardiovascular risk. Methods and Results Across 2 waves, 16 individuals with increased cardiovascular risk performed a 16-week intervention study (age 64±6 years, body mass index 29.9±4.3 kg/m2), using a device with vibration feedback to promote physical activity. Before and after intervention, we objectively examined physical activity (ActivPAL), cytokine production capacity after ex vivo stimulation in peripheral blood mononuclear cells, metabolism of peripheral blood mononuclear cells, circulating cytokine concentrations, and monocyte immunophenotype. Overall, no significant increase in walking time was found (1.9±0.7 to 2.2±1.2 h/day, P=0.07). However, strong, inverse correlations were observed between the change in walking time and the change in production of interleukin (IL)-1β, IL-6, IL-8, and IL-10 after lipopolysaccharide stimulation (rs=-0.655, -0.844, -0.672, and -0.781, respectively, all P<0.05). After intervention optimization based on feedback from wave 1, participants in wave 2 (n=8) showed an increase in walking time (2.2±0.8 to 3.0±1.3 h/day, P=0.001) and attenuated cytokine production of IL-6, IL-8, and IL-10 (all P<0.05). Glycolysis (P=0.08) and maximal OXPHOS (P=0.04) of peripheral blood mononuclear cells decreased after intervention. Lower IL-6 concentrations (P=0.06) and monocyte percentages (P<0.05), but no changes in monocyte subsets were found. Conclusions Successfully improving walking time shifts innate immune function towards a less proinflammatory state, characterized by a lower capacity to produce inflammatory cytokines, in individuals with increased cardiovascular risk

Broad Spectrum Antiviral Activity of Favipiravir (T-705): Protection from Highly Lethal Inhalational Rift Valley Fever

Background:Development of antiviral drugs that have broad-spectrum activity against a number of viral infections would be of significant benefit. Due to the evolution of resistance to currently licensed antiviral drugs, development of novel anti-influenza drugs is in progress, including Favipiravir (T-705), which is currently in human clinical trials. T-705 displays broad-spectrum in vitro activity against a number of viruses, including Rift Valley Fever virus (RVFV). RVF is an important neglected tropical disease that causes human, agricultural, and economic losses in endemic regions. RVF has the capacity to emerge in new locations and also presents a potential bioterrorism threat. In the current study, the in vivo efficacy of T-705 was evaluated in Wistar-Furth rats infected with the virulent ZH501 strain of RVFV by the aerosol route.Methodology/Principal Findings:Wistar-Furth rats are highly susceptible to a rapidly lethal disease after parenteral or inhalational exposure to the pathogenic ZH501 strain of RVFV. In the current study, two experiments were performed: a dose-determination study and a delayed-treatment study. In both experiments, all untreated control rats succumbed to disease. Out of 72 total rats infected with RVFV and treated with T-705, only 6 succumbed to disease. The remaining 66 rats (92%) survived lethal infection with no significant weight loss or fever. The 6 treated rats that succumbed survived significantly longer before succumbing to encephalitic disease.Conclusions/Significance:Currently, there are no licensed antiviral drugs for treating RVF. Here, T-705 showed remarkable efficacy in a highly lethal rat model of Rift Valley Fever, even when given up to 48 hours post-infection. This is the first study to show protection of rats infected with the pathogenic ZH501 strain of RVFV. Our data suggest that T-705 has potential to be a broad-spectrum antiviral drug. © 2014 Caroline et al

Lung carcinoma with hypertrophic osteoarthropathy in a teenager

Hypertrophic osteoarthropathy (HOA) characterised by arthralgia, clubbing and periosteal proliferation of long bones, is rarely encountered in children and adolescents. Whereas in adults over 80% of cases are associated with malignancy, in children the majority of cases are due to non-neoplastic causes such as cystic fibrosis, bilary atresia and congenital heart disease. Up to 5% of adults with lung cancer demonstrate signs of HOA. However, lung cancer is extremely uncommon in children and young people. Here we report a case of lung adenocarcinoma in an 18 year old male associated with HOA present both at diagnosis and at subsequent disease progression

Secondary headaches: secondary or still primary?

The second edition of the International Classification of Headache Disorders makes a distinction between primary and secondary headaches. The diagnosis of a secondary headache is made if the underlying disease is thought to cause headache or if a close temporal relationship is present together with the occurrence of the headache. At first glance, this may allow clearly secondary headaches to be distinguished from primary headaches. However, by reviewing the available literature concerning several selected secondary headaches, we will discuss the hypothesis that some secondary headaches can also be understood as a variation of primary headaches in the sense that the underlying cause (e.g. infusion of glyceryl trinitrate [ICHD-II 8.1.1], epilepsy [7.6.2], brain tumours [7.4], craniotomy [5.7], etc.) triggers the same neurophysiologic mechanisms that are responsible for the pain in primary headache attacks

Local Difference Measures between Complex Networks for Dynamical System Model Evaluation

Acknowledgments We thank Reik V. Donner for inspiring suggestions that initialized the work presented herein. Jan H. Feldhoff is credited for providing us with the STARS simulation data and for his contributions to fruitful discussions. Comments by the anonymous reviewers are gratefully acknowledged as they led to substantial improvements of the manuscript.Peer reviewedPublisher PD

Accreting Millisecond X-Ray Pulsars

Accreting Millisecond X-Ray Pulsars (AMXPs) are astrophysical laboratories without parallel in the study of extreme physics. In this chapter we review the past fifteen years of discoveries in the field. We summarize the observations of the fifteen known AMXPs, with a particular emphasis on the multi-wavelength observations that have been carried out since the discovery of the first AMXP in 1998. We review accretion torque theory, the pulse formation process, and how AMXP observations have changed our view on the interaction of plasma and magnetic fields in strong gravity. We also explain how the AMXPs have deepened our understanding of the thermonuclear burst process, in particular the phenomenon of burst oscillations. We conclude with a discussion of the open problems that remain to be addressed in the future.Comment: Review to appear in "Timing neutron stars: pulsations, oscillations and explosions", T. Belloni, M. Mendez, C.M. Zhang Eds., ASSL, Springer; [revision with literature updated, several typos removed, 1 new AMXP added

Behavioral Consequences of NMDA Antagonist-Induced Neuroapoptosis in the Infant Mouse Brain

Background: Exposure to NMDA glutamate antagonists during the brain growth spurt period causes widespread neuroapoptosis in the rodent brain. This period in rodents occurs during the first two weeks after birth, and corresponds to the third trimester of pregnancy and several years after birth in humans. The developing human brain may be exposed to NMDA antagonists through drug-abusing mothers or through anesthesia. Methodology/Principal Findings: We evaluated the long-term neurobehavioral effects of mice exposed to a single dose of the NMDA antagonist, phencyclidine (PCP), or saline, on postnatal day 2 (P2) or P7, or on both P2 and P7. PCP treatment on P2 + P7 caused more severe cognitive impairments than either single treatment. Histological examination of acute neuroapoptosis resulting from exposure to PCP indicated that the regional pattern of degeneration induced by PCP in P2 pups was different from that in P7 pups. The extent of damage when evaluated quantitatively on P7 was greater for pups previously treated on P2 compared to pups treated only on P7. Conclusions: These findings signify that PCP induces different patterns of neuroapoptosis depending on the developmental age at the time of exposure, and that exposure at two separate developmental ages causes more severe neuropathologica

A Functional Gene Array for Detection of Bacterial Virulence Elements

Emerging known and unknown pathogens create profound threats to public health. Platforms for rapid detection and characterization of microbial agents are critically needed to prevent and respond to disease outbreaks. Available detection technologies cannot provide broad functional information about known or novel organisms. As a step toward developing such a system, we have produced and tested a series of high-density functional gene arrays to detect elements of virulence and antibiotic resistance mechanisms. Our first generation array targets genes from Escherichia coli strains K12 and CFT073, Enterococcus faecalis and Staphylococcus aureus. We determined optimal probe design parameters for gene family detection and discrimination. When tested with organisms at varying phylogenetic distances from the four target strains, the array detected orthologs for the majority of targeted gene families present in bacteria belonging to the same taxonomic family. In combination with whole-genome amplification, the array detects femtogram concentrations of purified DNA, either spiked in to an aerosol sample background, or in combinations from one or more of the four target organisms. This is the first report of a high density NimbleGen microarray system targeting microbial antibiotic resistance and virulence mechanisms. By targeting virulence gene families as well as genes unique to specific biothreat agents, these arrays will provide important data about the pathogenic potential and drug resistance profiles of unknown organisms in environmental samples