Cardiac myosin activation: a potential therapeutic approach for systolic heart failure

Decreased cardiac contractility is a central feature of systolic heart failure. Existing drugs increase cardiac contractility indirectly through signaling cascades but are limited by their mechanism-related adverse effects. To avoid these limitations, we previously developed omecamtiv mecarbil, a small-molecule, direct activator of cardiac myosin. Here, we show that it binds to the myosin catalytic domain and operates by an allosteric mechanism to increase the transition rate of myosin into the strongly actin-bound force-generating state. Paradoxically, it inhibits adenosine 5'-triphosphate turnover in the absence of actin, which suggests that it stabilizes an actin-bound conformation of myosin. In animal models, omecamtiv mecarbil increases cardiac function by increasing the duration of ejection without changing the rates of contraction. Cardiac myosin activation may provide a new therapeutic approach for systolic heart failure.     

Detection of anthropogenic climate change in the world's oceans

Large-scale increases in the heat content of the world's oceans have been observed to occur over the last 45 years. The horizontal and temporal character of these changes has been closely replicated by the state-of-the-art Parallel Climate Model (PCM) forced by observed and estimated anthropogenic gases. Application of optimal detection methodology shows that the model-produced signals are indistinguishable from the observations at the 0.05 confidence level. Further, the chances of either the anthropogenic or observed signals being produced by the PCM as a result of natural, internal forcing alone are less than 5%. This suggests that the observed ocean heat-content changes are consistent with those expected from anthropogenic forcing, which broadens the basis for claims that an anthropogenic signal has been detected in the global climate system. Additionally, the requirement that modeled ocean heat uptakes match observations puts a strong, new constraint on anthropogenically forced climate models. It is unknown if the current generation of climate models, other than the PCM, meet this constraint.     

Use of the Cell-Dyn 3500 to predict leukemic cell lineage in peripheral blood of dogs and cats

Background— Morphology and cytochemistry are the foundation for classification of leukemias in dogs and cats. Advances in automated hematology instrumentation, immunophenotyping, cytogenetics, and molecular biology are significantly improving our ability to recognize and classify spontaneous myeloproliferative and lymphoproliferative disorders. Objective— The purpose of this study was to assess the utility of flow cytometry‐based light scatter patterns provided by the Cell‐Dyn 3500 (CD3500) automated hematology analyzer to predict the lineage of leukemic cells in peripheral blood of dogs and cats. Methods— Leukemic cells from 15 dogs and 6 cats were provisionally classified using an algorithm based on the CD3500 CBC output data and were subsequently phenotyped by enzyme cytochemistry, immunocytochemistry, indirect flow cytometry, and analysis of antigen receptor gene rearrangement. Results— The algorithm led to correct predictions regarding the ontogeny of the leukemic cells (erythroid/megakaryocytic potential, myeloid leukemia, monocytic leukemia, chronic granulocytic leukemia, lymphoid leukemia) in 19/21 animals. Mismatches in the WBC impedance count and the WBC optical count in conjunction with microscopic assessment of blasts in the blood were useful for predicting myeloproliferative disorders with erythroid or megakaryocytic potential. The leukocyte light scatter patterns enabled distinction among myeloid leukemias (represented by acute myelomonocytic leukemia, acute monocytic leukemia, chronic granulocytic leukemia) and lymphocytic leukemias (including acute and chronic lymphocytic leukemias). One case of acute lymphocytic leukemia was misidentified as chronic lymphocytic leukemia. Conclusions— Algorithmic analyses can be applied to data generated by the CD3500 to predict the ontogeny of leukemic cells in the peripheral blood of dogs and cats. This rapid and quantitative technique may be used to improve diagnostic decisions, expand therapeutic choices, and increase prognostic accuracy.     

A Remote Irrigation Monitoring and Control System for continuous move systems. Part A: description and development

Continuous move irrigation systems have been modified since the 1990s to support variable rate irrigation. Most of these systems used PLC (Programmable Logic Controllers) technology that performed well for on-site control but were very expensive to add remote, real-time monitoring and control aspects that have been made possible by wireless sensor networks and the Internet. A new approach to the monitoring and control of continuous move irrigation systems is described. This system uses a Single Board Computer (SBC) using the Linux operating system to control solenoids connected to individual or groups of nozzles based on prescribed application maps. The main control box houses the SBC connected to a sensor network radio, a GPS (Global Positioning System) unit, and an Ethernet radio creating a wireless connection to a remote server. A C-software control program resides on the SBC to control the on/off time for each nozzle group using a “time on” application map developed remotely. The SBC also interfaces with the sensor network radio to record measurements from sensors on the irrigation system and in the field that monitor performance and soil and crop conditions. The SBC automatically populates a remote database on the server in real time and provides software applications to monitor and control the irrigation system through the Internet.     

Nearly singular magnetic fluctuations in the normal state of a high-Tc cuprate superconductor

Polarized and unpolarized neutron scattering was used to measure the wave vector- and frequency-dependent magnetic fluctuations in the normal state (from the superconducting transition temperature, Tc = 35 kelvin, up to 350 kelvin) of single crystals of La1.86Sr0.14CuO4. The peaks that dominate the fluctuations have amplitudes that decrease as T-2 and widths that increase in proportion to the thermal energy, kBT (where kB is Boltzmann's constant), and energy transfer added in quadrature. The nearly singular fluctuations are consistent with a nearby quantum critical point.     

Organic mercury identified as the cause of poisoning in humans and hogs

Atomic absorption spectrophotometry and neutron activation analysis showed the presence of mercury in organic extracts of seed grain and in tissues of hogs fed the contaminated grain. Mercury was also found in the urine, serum, and cerebrospinal fluid of humans who ate the contaminated pork. Mass spectral analysis confirmed the presence of organic mercury. This paper reports the first documented episode of indirect mercury poisoning in humans in the United States caused by the ingestion of contaminated meat from animals that had consumed mercury in their food supply.     

Copper-Catalyzed Oxidation of Alcohols to Aldehydes and Ketones: An Efficient, Aerobic Alternative

An efficient, copper-based catalyst has been discovered that oxidizes a wide range of alcohols into aldehydes and ketones under mild conditions. This catalytic system utilizes oxygen or air as the ultimate, stoichiometric oxidant, producing water as the only by-product.