Draft Genome Sequences of Strains TAV3 and TAV4 (Verrucomicrobia: Opitutaceae), Isolated from a Wood-Feeding Termite, and In Silico Analysis of Their Polysaccharide-Degrading Enzymes.

Here, we report the high-quality draft genome sequences of Opitutaceae sp. strains TAV3 and TAV4, which were isolated from the hindgut of the wood-feeding termite Reticulitermes flavipes Using a combination of Illumina and PacBio sequencing, we constructed nearly complete assemblies totaling 5.84 and 5.91 Mbp in length for strains TAV3 and TAV4, respectively. In addition, we report an in silico analysis of potential lignocellulose-digesting enzymes present in these strains

Ectopy on a single 12‐lead ECG, incident cardiac myopathy, and death in the community

BackgroundAtrial fibrillation and heart failure are 2 of the most common diseases, yet ready means to identify individuals at risk are lacking. The 12-lead ECG is one of the most accessible tests in medicine. Our objective was to determine whether a premature atrial contraction observed on a standard 12-lead ECG would predict atrial fibrillation and mortality and whether a premature ventricular contraction would predict heart failure and mortality.Methods and resultsWe utilized the CHS (Cardiovascular Health) Study, which followed 5577 participants for a median of 12 years, as the primary cohort. The ARIC (Atherosclerosis Risk in Communities Study), the replication cohort, captured data from 15 792 participants over a median of 22 years. In the CHS, multivariable analyses revealed that a baseline 12-lead ECG premature atrial contraction predicted a 60% increased risk of atrial fibrillation (hazard ratio, 1.6; 95% CI, 1.3-2.0; P<0.001) and a premature ventricular contraction predicted a 30% increased risk of heart failure (hazard ratio, 1.3; 95% CI, 1.0-1.6; P=0.021). In the negative control analyses, neither predicted incident myocardial infarction. A premature atrial contraction was associated with a 30% increased risk of death (hazard ratio, 1.3; 95% CI, 1.1-1.5; P=0.008) and a premature ventricular contraction was associated with a 20% increased risk of death (hazard ratio, 1.2; 95% CI, 1.0-1.3; P=0.044). Similarly statistically significant results for each analysis were also observed in ARIC.ConclusionsBased on a single standard ECG, a premature atrial contraction predicted incident atrial fibrillation and death and a premature ventricular contraction predicted incident heart failure and death, suggesting that this commonly used test may predict future disease

Joint computation and communication design for UAV-assisted mobile edge computing in IoT

Unmanned aerial vehicle (UAV)-assisted mobile edge computing (MEC) system is a prominent concept, where a UAV equipped with a MEC server is deployed to serve a number of terminal devices (TDs) of Internet of Things (IoT) in a finite period. In this paper, each TD has a certain latency-critical computation task in each time slot to complete. Three computation strategies can be available to each TD. First, each TD can operate local computing by itself. Second, each TD can partially offload task bits to the UAV for computing. Third, each TD can choose to offload task bits to access point (AP) via UAV relaying. We propose an optimization problem formulation that aims to minimize the total energy consumption including communication-related energy, computation-related energy and UAV flight energy by optimizing the bits allocation, time slot scheduling and power allocation as well as UAV trajectory design. As the formulated problem is nonconvex and difficult to find the optimal solution, we propose to solve the problem by two parts, and obtain the near optimal solution by the Lagrangian duality method and successive convex approximation (SCA) technique, respectively. By analysis, the proposed algorithm can be guaranteed to converge within a dozen of iterations. Finally, numerical results are given to validate the proposed algorithm, which is verified to be efficient and superior to the other benchmark cases

Excitation and modulation of TRPA1, TRPV1, and TRPM8 channel-expressing sensory neurons by the pruritogen chloroquine

The sensations of pain, itch, and cold often interact with each other. Pain inhibits itch, whereas cold inhibits both pain and itch. TRPV1 and TRPA1 channels transduce pain and itch, whereas TRPM8 transduces cold. The pruritogen chloroquine (CQ) was reported to excite TRPA1, leading to the sensation of itch. It is unclear how CQ excites and modulates TRPA1+, TRPV1+, and TRPM8+ neurons and thus affects the sensations of pain, itch, and cold. Here, we show that only 43% of CQ-excited dorsal root ganglion neurons expressed TRPA1; as expected, the responses of these neurons were completely prevented by the TRPA1 antagonist HC-030031. The remaining 57% of CQ-excited neurons did not express TRPA1, and excitation was not prevented by either a TRPA1 or TRPV1 antagonist but was prevented by the general transient receptor potential canonical (TRPC) channel blocker BTP2 and the selective TRPC3 inhibitor Pyr3. Furthermore, CQ caused potent sensitization of TRPV1 in 51.9% of TRPV1+ neurons and concomitant inhibition of TRPM8 in 48.8% of TRPM8+ dorsal root ganglion neurons. Sensitization of TRPV1 is caused mainly by activation of the phospholipase C-PKC pathway following activation of the CQ receptor MrgprA3. By contrast, inhibition of TRPM8 is caused by a direct action of activated Gαq independent of the phospholipase C pathway. Our data suggest the involvement of the TRPC3 channel acting together with TRPA1 to mediate CQ-induced itch. CQ not only elicits itch by directly exciting itch-encoding neurons but also exerts previously unappreciated widespread actions on pain-, itch-, and cold-sensing neurons, leading to enhanced pain and itch

Antitumor Activity of Pembrolizumab in Biomarker-Unselected Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: Results From the Phase Ib KEYNOTE-012 Expansion Cohort.

Purpose Treatment with pembrolizumab, an anti-programmed death-1 antibody, at 10 mg/kg administered once every 2 weeks, displayed durable antitumor activity in programmed death-ligand 1 (PD-L1) -positive recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) in the KEYNOTE-012 trial. Results from the expansion cohort, in which patients with HNSCC, irrespective of biomarker status, received a fixed dose of pembrolizumab at a less frequent dosing schedule, are reported. Patients and Methods Patients with R/M HNSCC, irrespective of PD-L1 or human papillomavirus status, received pembrolizumab 200 mg intravenously once every 3 weeks. Imaging was performed every 8 weeks. Primary end points were overall response rate (ORR) per central imaging vendor (Response Evaluation Criteria in Solid Tumors v1.1) and safety. Secondary end points included progression-free survival, overall survival, and association of response and PD-L1 expression. Patients who received one or more doses of pembrolizumab were included in analyses. Results Of 132 patients enrolled, median age was 60 years (range, 25 to 84 years), 83% were male, and 57% received two or more lines of therapy for R/M disease. ORR was 18% (95% CI, 12 to 26) by central imaging vendor and 20% (95% CI, 13 to 28) by investigator review. Median duration of response was not reached (range, ≥ 2 to ≥ 11 months). Six-month progression-free survival and overall survival rates were 23% and 59%, respectively. By using tumor and immune cells, a statistically significant increase in ORR was observed for PD-L1-positive versus -negative patients (22% v 4%; P = .021). Treatment-related adverse events of any grade and grade ≥ 3 events occurred in 62% and 9% of patients, respectively. Conclusion Fixed-dose pembrolizumab 200 mg administered once every 3 weeks was well tolerated and yielded a clinically meaningful ORR with evidence of durable responses, which supports further development of this regimen in patients with advanced HNSCC

Strings on Bubbling Geometries

We study gauge theory operators which take the form of a product of a trace with a Schur polynomial, and their string theory duals. These states represent strings excited on bubbling AdS geometries which are dual to the Schur polynomials. These geometries generically take the form of multiple annuli in the phase space plane. We study the coherent state wavefunction of the lattice, which labels the trace part of the operator, for a general Young tableau and their dual description on the droplet plane with a general concentric ring pattern. In addition we identify a density matrix over the coherent states on all the geometries within a fixed constraint. This density matrix may be used to calculate the entropy of a given ensemble of operators. We finally recover the BMN string spectrum along the geodesic near any circle from the ansatz of the coherent state wavefunction.Comment: 41 pages, 12 figures, published version in JHE