Design by Measure and Conquer, A Faster Exact Algorithm for Dominating Set

The measure and conquer approach has proven to be a powerful tool to analyse exact algorithms for combinatorial problems, like Dominating Set and Independent Set. In this paper, we propose to use measure and conquer also as a tool in the design of algorithms. In an iterative process, we can obtain a series of branch and reduce algorithms. A mathematical analysis of an algorithm in the series with measure and conquer results in a quasiconvex programming problem. The solution by computer to this problem not only gives a bound on the running time, but also can give a new reduction rule, thus giving a new, possibly faster algorithm. This makes design by measure and conquer a form of computer aided algorithm design. When we apply the methodology to a Set Cover modelling of the Dominating Set problem, we obtain the currently fastest known exact algorithms for Dominating Set: an algorithm that uses $O(1.5134^n)$ time and polynomial space, and an algorithm that uses $O(1.5063^n)$ time

Cut and Count and Representative Sets on Branch Decompositions

Recently, new techniques have been introduced to speed up dynamic programming algorithms on tree decompositions for connectivity problems: the \u27Cut and Count\u27 method and a method called the rank-based approach, based on representative sets and Gaussian elimination. These methods respectively give randomised and deterministic algorithms that are single exponential in the treewidth, and polynomial, respectively linear in the number of vertices. In this paper, we adapt these methods to branch decompositions yielding algorithms, both randomised and deterministic, that are in many cases faster than when tree decompositions would be used. In particular, we obtain the currently fastest randomised algorithms for several problems on planar graphs. When the involved weights are O(n^{O(1)}), we obtain faster randomised algorithms on planar graphs for Steiner Tree, Connected Dominating Set, Feedback Vertex Set and TSP, and a faster deterministic algorithm for TSP. When considering planar graphs with arbitrary real weights, we obtain faster deterministic algorithms for all four mentioned problems

Effect of a high-voltage mesh electrode on the volume and surface characteristics of pulsed dielectric barrier discharges

Electrical breakdown in a pulsed asymmetric dielectric barrier discharge between a glass-covered mesh electrode and a grounded metal electrode in the air at atmospheric pressure is investigated. Volume discharge forms between the metal tip and the dielectric surface and spreads over the dielectric surface. Breakdown and discharge behaviors depend on the polarity of the charged electrode covered with glass compared to the metal rod electrode. In the case of the dielectric cathode (covered mesh), volume discharge features a stronger and longer-lasting emission. Volume discharge is weaker with outstretched surface discharge developing on the opposite glass electrode sustained by the embedded mesh when the metal rod functions as a cathode. The development and spatial distribution of the surface discharge depend on the relative polarity of the dielectrics caused by the charge deposition of the preceding discharge and is independent of the polarity of the applied high voltage. The discharge emission is brighter for the metal cathode and dielectric anode than for the metal anode, with a branching discharge developing and spreading in a star-like structure along the embedded grid, while a ring-like structure was observed for the metal anode and dielectric cathode. The duty cycle influences the discharge development and properties through the effects of the gas phase and surface pre-ionization

Cyclic-AMP mediated drugs: differential or global reduction of eicosanoid synthesis in the isolated rat lung?

In this study the question was addressed whether cAMP mediated drugs induce a differential reduction of branches of the arachidonic acid metabolism rather than a global reduction of eicosanoid synthesis. The isolated lungs of actively sensitized rats were employed to study prostaglandin and leukotriene release in the presence and absence of the cAMP mediated drugs theophylline, milrinone, sulmazole, isobutyl-methylxanthine and salbutamol. The release of eicosanoids as measured by RIA was predominantly basal and continuous, with a mild antigen induced stimulation only for TXB2 and the leukotrienes. All drugs reduced eicosanoid release globally. It is concluded that cAMP mediated drugs interfere with arachidonic acid metabolism at a site proximal to the branching into lipoxygenase and cyclo-oxygenase pathways

Transcriptional Activity and Stability of CD39+CD103+CD8+T Cells in Human High-Grade Endometrial Cancer

Tumor-infiltrating CD8+ T cells (TIL) are of the utmost importance in anti-tumor immunity. CD103 defines tumor-resident memory T cells (T-RM cells) associated with improved survival and response to immune checkpoint blockade (ICB) across human tumors. Co-expression of CD39 and CD103 marks tumor-specific T-RM with enhanced cytolytic potential, suggesting that CD39+CD103+ T-RM could be a suitable biomarker for immunotherapy. However, little is known about the transcriptional activity of T-RM cells in situ. We analyzed CD39+CD103+ T-RM cells sorted from human high-grade endometrial cancers (n = 3) using mRNA sequencing. Cells remained untreated or were incubated with PMA/ionomycin (activation), actinomycin D (a platinum-like chemotherapeutic that inhibits transcription), or a combination of the two. Resting CD39+CD103+ T-RM cells were transcriptionally active and expressed a characteristic T-RM signature. Activated CD39+CD103+ T-RM cells differentially expressed PLEK, TWNK, and FOS, and cytokine genes IFNG, TNF, IL2, CSF2 (GM-CSF), and IL21. Findings were confirmed using qPCR and cytokine production was validated by flow cytometry of cytotoxic TIL. We studied transcript stability and found that PMA-responsive genes and mitochondrial genes were particularly stable. In conclusion, CD39+CD103+ T-RM cells are transcriptionally active T-RM cells with a polyfunctional, reactivation-responsive repertoire. Secondly, we hypothesize that differential regulation of transcript stability potentiates rapid responses upon T-RM reactivation in tumors

Acetaminophen for self-reported sleep problems in an elderly population (ASLEEP): Study protocol of a randomized placebo-controlled double-blind trial

Background: The prevalence of sleep disorders increases with age. Sleep disorders may have serious health implications and may be related to serious underlying diseases. Many older people use hypnotics, like benzodiazepines, although these medications have serious side effects and often lead to habituation. Acetaminophen is one of the most frequently used off-label drugs for sleep disorders, although little is known about its effects. Our objective is to investigate whether acetaminophen is effective in treating self-reported sleep disorders in older people. Methods/Design: Participants, aged 65 years or older (n = 150), who have sleep disorders will be randomized for treatment with either acetaminophen 1000 mg or placebo, once daily at bedtime in a double-blind design. Eligible patients should be able to give informed consent, should not be cognitively impaired (Minimal Mental State Examination (MMSE) score ≥ 20), should not have pain, and should not use acetaminophen on a regular basis because of pain complaints. The study will take three weeks to complete. During these three weeks, the participants register their sleep behavior in a sleep diary. The participants will use the study medication during the second and third week. The primary endpoint will be the self-reported sleep disorders at the end of week three, as measured by means of the Insomnia Severity Index (ISI). To validate these subjective sleep parameters against objectively measured indices of the sleep-wake pattern, we will measure the periods of wakefulness and sleep in a subgroup of participants, using an actigraph worn on the wrist during the entire study period. Discussion: The proposed study will contribute to our knowledge about the treatment of sleep disorders in an older population. There is a need for treatments for sleep disorders without serious adverse effects. Acetaminophen might be a simple and inexpensive alternative for the regimes that are currently used with older people. Trial registration: The Netherlands National Trial Register NTR2747

Tattoo Delivery of a Semliki Forest Virus-Based Vaccine Encoding Human Papillomavirus E6 and E7

The skin is an attractive organ for immunization because of the presence of antigen-presenting cells. Intradermal delivery via tattooing has demonstrated superior vaccine immunogenicity of DNA vaccines in comparison to conventional delivery methods. In this study, we explored the efficacy of tattoo injection of a tumor vaccine based on recombinant Semliki Forest virus replicon particles (rSFV) targeting human papillomavirus (HPV). Tattoo injection of rSFV particles resulted in antigen expression in both the skin and draining lymph nodes. In comparison with intramuscular injection, the overall antigen expression determined at the site of administration and draining lymph nodes was 10-fold lower upon tattoo injection. Delivery of SFV particles encoding the E6 and E7 antigens of human papillomavirus type 16 (SFVeE6,7) via tattooing resulted in HPV-specific cytotoxic T cells and in vivo therapeutic antitumor response. Strikingly, despite the observed lower overall transgene expression, SFVeE6,7 delivered via tattoo injection resulted in higher or equal levels of immune responses as compared to intramuscular injection. The intrinsic immunogenic potential of tattooing provides a benefit for immunotherapy based on an alphavirus