Transient Silencing of a Type IV P-Type ATPase, Atp10c, Results in Decreased Glucose Uptake in C2C12 Myotubes

Atp10c is a strong candidate gene for diet-induced obesity and type 2 diabetes. To identify molecular and cellular targets of ATP10C, Atp10c expression was altered in vitro in C2C12 skeletal muscle myotubes by transient transfection with an Atp10c-specific siRNA. Glucose uptake assays revealed that insulin stimulation caused a significant 2.54-fold decrease in 2-deoxyglucose uptake in transfected cells coupled with a significant upregulation of native mitogen-activated protein kinases (MAPKs), p38, and p44/42. Additionally, glucose transporter-1 (GLUT1) was significantly upregulated; no changes in glucose transporter-4 (GLUT4) expression were observed. The involvement of MAPKs was confirmed using the specific inhibitor SB203580, which downregulated the expression of native and phosphorylated MAPK proteins in transfected cells without any changes in insulin-stimulated glucose uptake. Results indicate that Atp10c regulates glucose metabolism, at least in part via the MAPK pathway, and, thus, plays a significant role in the development of insulin resistance and type 2 diabetes

Correlated Lightning Mapping Array (LMA) and Radar Observations of the Initial Stages of Florida Triggered Lightning Discharges

We characterize the geometrical and electrical characteristics of the initial stages of nine Florida triggered lightning discharges using a Lightning Mapping Array (LMA), a C-band SMART radar, and measured channel-base currents. We determine initial channel and subsequent branch lengths, average initial channel and branch propagation speeds, and channel-base current at the time of each branch initiation. The channel-base current is found to not change significantly when branching occurs, an unexpected result. The initial stage of Florida triggered lightning typically transitions from vertical to horizontal propagation at altitudes of 3-6 km, near the typical 0 C level of 4-5 km and several kilometers below the expected center of the negative cloud-charge region at 7-8 km. The data presented potentially provide information on thunderstorm electrical and hydrometeor structure and discharge propagation physics. LMA source locations were obtained from VHF sources of positive impulsive currents as small as 10 A, in contrast to expectations found in the literature

Influenza-like Illness, the Time to Seek Healthcare, and Influenza Antiviral Receipt During the 2010–2011 Influenza Season— United States

Background. Few data exist describing healthcare-seeking behaviors among persons with influenza-like illness (ILI) or adherence to influenza antiviral treatment recommendations. Methods. We analyzed adult responses to the Behavioral Risk Factor Surveillance System in 31 states and the District of Columbia (DC) and pediatric responses in 25 states and DC for January–April 2011 by demographics and underlying health conditions. Results. Among 75 088 adult and 15 649 child respondents, 8.9% and 33.9%, respectively, reported ILI. ILI was more frequent among adults with asthma (16%), chronic obstruction pulmonary disease (COPD; 26%), diabetes (12%), heart disease (19%), kidney disease (16%), or obesity (11%). Forty-five percent of adults and 57% of children sought healthcare for ILI. Thirty-five percent of adults sought care ≤2 days after ILI onset. Seeking care ≤2 days was more frequent among adults with COPD (48%) or heart disease (55%). Among adults with a self-reported physician diagnosis of influenza, 34% received treatment with antiviral medications. The only underlying health condition with a higher rate of treatment was diabetes (46%). Conclusions. Adults with underlying health conditions were more likely to report ILI, but the majority did not seek care promptly, missing opportunities for early influenza antiviral treatment

Two-photon quantum walks in an elliptical direct-write waveguide array

Integrated optics provides an ideal test bed for the emulation of quantum systems via continuous-time quantum walks. Here we study the evolution of two-photon states in an elliptic array of waveguides. We characterise the photonic chip via coherent-light tomography and use the results to predict distinct differences between temporally indistinguishable and distinguishable two-photon inputs which we then compare with experimental observations. Our work highlights the feasibility for emulation of coherent quantum phenomena in three-dimensional waveguide structures.Comment: 8 pages, 7 figure

Generic Model Refactorings

Many modeling languages share some common concepts and principles. For example, Java, MOF, and UML share some aspects of the concepts\ud of classes, methods, attributes, and inheritance. However, model\ud transformations such as refactorings specified for a given language\ud cannot be readily reused for another language because their related\ud metamodels may be structurally different. Our aim is to enable a\ud flexible reuse of model transformations across various metamodels.\ud Thus, in this paper, we present an approach allowing the specification\ud of generic model transformations, in particular refactorings, so\ud that they can be applied to different metamodels. Our approach relies\ud on two mechanisms: (1) an adaptation based mainly on the weaving\ud of aspects; (2) the notion of model typing, an extension of object\ud typing in the model-oriented context. We validated our approach by\ud performing some experiments that consisted of specifying three well\ud known refactorings (Encapsulate Field, Move Method, and Pull Up Method)\ud and applying each of them onto three different metamodels (Java,\ud MOF, and UML)

Towards a software product line of trie-based collections

Collection data structures in standard libraries of programming languages are designed to excel for the average case by carefully balancing memory footprint and runtime performance. These implicit design decisions and hard-coded trade-offs do constrain users from using an optimal variant for a given problem. Although a wide range of specialized collections is available for the Java Virtual Machine (JVM), they introduce yet another dependency and complicate user adoption by requiring specific Application Program Interfaces (APIs) incompatible with the standard library. A product line for collection data structures would relieve library designers from optimizing for the general case. Furthermore, a product line allows evolving the potentially large code base of a collection family efficiently. The challenge is to find a small core framework for collection data structures which covers all variations without exhaustively listing them, while supporting good performance at the same time. We claim that the concept of Array Mapped Tries (AMTs) embodies a high degree of commonality in the sub-domain of immutable collection data structures. AMTs are flexible enough to cover most of the variability, while minimizing code bloat in the generator and the generated code. We implemented a Data Structure Code Generator (DSCG) that emits immutable collections based on an AMT skeleton foundation. The generated data structures outperform competitive handoptimized implementations, and the generator still allows for customization towards specific workloads

Evaluation of Biased and Balanced Salvinorin A Analogs in Preclinical Models of Pain

This work is licensed under a Creative Commons Attribution 4.0 International License.In the search for safer, non-addictive analgesics, kappa opioid receptor (KOPr) agonists are a potential target, as unlike mu-opioid analgesics, they do not have abuse potential. Salvinorin A (SalA) is a potent and selective KOPr agonist, however, clinical utility is limited by the short duration of action and aversive side effects. Biasing KOPr signaling toward G-protein activation has been highlighted as a key cellular mechanism to reduce the side effects of KOPr agonists. The present study investigated KOPr signaling bias and the acute antinociceptive effects and side effects of two novel analogs of SalA, 16-Bromo SalA and 16-Ethynyl SalA. 16-Bromo SalA showed G-protein signaling bias, whereas 16-Ethynyl SalA displayed balanced signaling properties. In the dose-response tail-withdrawal assay, SalA, 16-Ethynyl SalA and 16-Bromo SalA were more potent than the traditional KOPr agonist U50,488, and 16-Ethynyl SalA was more efficacious. 16-Ethynyl SalA and 16-Bromo SalA both had a longer duration of action in the warm water tail-withdrawal assay, and 16-Ethynyl had greater antinociceptive effect in the hot-plate assay, compared to SalA. In the intraplantar 2% formaldehyde test, 16-Ethynyl SalA and 16-Bromo SalA significantly reduced both nociceptive and inflammatory pain-related behaviors. Moreover, 16-Ethynyl SalA and 16-Bromo SalA had no anxiogenic effects in the marble burying task, and 16-Bromo SalA did not alter behavior in the elevated zero maze. Overall, 16-Ethynyl SalA significantly attenuated acute pain-related behaviors in multiple preclinical models, while the biased KOPr agonist, 16-Bromo SalA, displayed modest antinociceptive effects, and lacked anxiogenic effects.Health Research Council – Explorer grant (16/646)National Institute on Drug Abuse (DA018151)Victoria University of Wellington doctoral scholarshi

Audience responses to representations of family-assisted suicide on British television

Reflecting on different generic conventions, this study highlights the strengths and weaknesses of documentaries and soap operas in addressing the societal and the personal dimensions of family-assisted suicide. Based on an analysis of YouTube user comments, this study compares how audience members respond to representations of family-assisted suicide in British documentaries and soap operas broadcast between 2010 and 2016. The thematic analysis of comments shows key differences between audience engagement with factual and fictional representations. Markers of a political engagement with this sensitive social issue occur more frequently in comments on documentaries than in comments on soap operas. Comments on soap operas are frequently expressions of emotion, or displays of specialist soap opera knowledge

Optical one-way quantum computing with a simulated valence-bond solid

One-way quantum computation proceeds by sequentially measuring individual spins (qubits) in an entangled many-spin resource state. It remains a challenge, however, to efficiently produce such resource states. Is it possible to reduce the task of generating these states to simply cooling a quantum many-body system to its ground state? Cluster states, the canonical resource for one-way quantum computing, do not naturally occur as ground states of physical systems. This led to a significant effort to identify alternative resource states that appear as ground states in spin lattices. An appealing candidate is a valence-bond-solid state described by Affleck, Kennedy, Lieb, and Tasaki (AKLT). It is the unique, gapped ground state for a two-body Hamiltonian on a spin-1 chain, and can be used as a resource for one-way quantum computing. Here, we experimentally generate a photonic AKLT state and use it to implement single-qubit quantum logic gates.Comment: 11 pages, 4 figures, 8 tables - added one referenc