Usage of NASA's Near Real-Time Solar and Meteorological Data for Monitoring Building Energy Systems Using RETScreen International's Performance Analysis Module

This paper describes building energy system production and usage monitoring using examples from the new RETScreen Performance Analysis Module, called RETScreen Plus. The module uses daily meteorological (i.e., temperature, humidity, wind and solar, etc.) over a period of time to derive a building system function that is used to monitor building performance. The new module can also be used to target building systems with enhanced technologies. If daily ambient meteorological and solar information are not available, these are obtained over the internet from NASA's near-term data products that provide global meteorological and solar information within 3-6 days of real-time. The accuracy of the NASA data are shown to be excellent for this purpose enabling RETScreen Plus to easily detect changes in the system function and efficiency. This is shown by several examples, one of which is a new building at the NASA Langley Research Center that uses solar panels to provide electrical energy for building energy and excess energy for other uses. The system shows steady performance within the uncertainties of the input data. The other example involves assessing the reduction in energy usage by an apartment building in Sweden before and after an energy efficiency upgrade. In this case, savings up to 16% are shown

eIF2α phosphorylation controls thermal nociception

A response to environmental stress is critical to alleviate cellular injury and maintain cellular homeostasis. Eukaryotic initiation factor 2 (eIF2) is a key integrator of cellular stress responses and an important regulator of mRNA translation. Diverse stress signals lead to the phosphorylation of the α subunit of eIF2 (Ser51), resulting in inhibition of global protein synthesis while promoting expression of proteins that mediate cell adaptation to stress. Here we report that eIF2α is instrumental in the control of noxious heat sensation. Mice with decreased eIF2α phosphorylation (eIF2α(+/S51A)) exhibit reduced responses to noxious heat. Pharmacological attenuation of eIF2α phosphorylation decreases thermal, but not mechanical, pain sensitivity, whereas increasing eIF2α phosphorylation has the opposite effect on thermal nociception. The impact of eIF2α phosphorylation (p-eIF2α) on thermal thresholds is dependent on the transient receptor potential vanilloid 1. Moreover, we show that induction of eIF2α phosphorylation in primary sensory neurons in a chronic inflammation pain model contributes to thermal hypersensitivity. Our results demonstrate that the cellular stress response pathway, mediated via p-eIF2α, represents a mechanism that could be used to alleviate pathological heat sensation

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Cell-Specific Retrograde Signals Mediate Antiparallel Effects of Angiotensin II on Osmoreceptor Afferents to Vasopressin and Oxytocin Neurons

Homeostatic control of extracellular fluid osmolality in rats requires a parallel excitation of vasopressin (VP) and oxytocin (OT) neurosecretory neurons by osmoreceptor afferents to regulate the amount of water and sodium in the urine under normal conditions. However, during decreased blood volume (hypovolemia), natriuresis is suppressed, whereas osmotically driven antidiuresis is enhanced to promote retention of isotonic fluid. Because Angiotensin II (Ang II) is released centrally to indicate hypovolemia, we hypothesized that Ang II can evoke a state-dependent switch in circuit function. Here, we show that Ang II, a neuropeptide released centrally during hypovolemia, suppresses osmoreceptor-mediated synaptic excitation of OT neurons while potentiating excitation of VP neurons. Ang II does this by inducing cell-autonomous release of nitric oxide by VP neurons and endocannabinoids by OT neurons to respectively enhance and reduce glutamate release by osmoreceptor afferents. These findings indicate that peptide modulators such as Ang II can regulate synaptic communication to achieve a state-dependent and target-specific modulation of circuit activity

Taurine Release by Astrocytes Modulates Osmosensitive Glycine Receptor Tone and Excitability in the Adult Supraoptic Nucleus

Cells can release the free amino acid taurine through volume-regulated anion channels (VRACs), and it has been hypothesized that taurine released from glial cells is capable of inhibiting action potential (AP) firing by activating neuronal glycine receptors (GlyRs) (Hussy et al., 1997). Although an inhibitory GlyR tone is widely observed in the brain, it remains unknown whether this specifically reflects gliotransmission because most neurons also express VRACs and other endogenous molecules can activate GlyRs. We found that VRACs are absent in neurons of the rat supraoptic nucleus (SON), suggesting that glial cells are the exclusive source of taurine in this nucleus. Application of strychnine to rat hypothalamic explants caused a depolarization of SON neurons associated with a decrease of chloride conductance and could excite these cells in the absence of fast synaptic transmission. This inhibitory GlyR tone was eliminated by pharmacological blockade of VRACs, by cellular taurine depletion, by metabolic inactivation of glia with fluorocitrate, and after retraction of astrocytic processes that intercalate neuronal somata and dendrites. Finally, GlyR tone varied inversely with extracellular fluid tonicity to mediate the osmotic control of AP firing by SON neurons. These findings establish taurine as a physiological gliotransmitter and show that gliotransmission is a spatially constrained process that can be modulated by the morphological rearrangement of astrocytes

Taurine Release by Astrocytes Modulates Osmosensitive Glycine Receptor Tone and Excitability in the Adult Supraoptic Nucleus

Cells can release the free amino acid taurine through volume-regulated anion channels (VRACs), and it has been hypothesized that taurine released from glial cells is capable of inhibiting action potential (AP) firing by activating neuronal glycine receptors (GlyRs) (Hussy et al., 1997). Although an inhibitory GlyR tone is widely observed in the brain, it remains unknown whether this specifically reflects gliotransmission because most neurons also express VRACs and other endogenous molecules can activate GlyRs. We found that VRACs are absent in neurons of the rat supraoptic nucleus (SON), suggesting that glial cells are the exclusive source of taurine in this nucleus. Application of strychnine to rat hypothalamic explants caused a depolarization of SON neurons associated with a decrease of chloride conductance and could excite these cells in the absence of fast synaptic transmission. This inhibitory GlyR tone was eliminated by pharmacological blockade of VRACs, by cellular taurine depletion, by metabolic inactivation of glia with fluorocitrate, and after retraction of astrocytic processes that intercalate neuronal somata and dendrites. Finally, GlyR tone varied inversely with extracellular fluid tonicity to mediate the osmotic control of AP firing by SON neurons. These findings establish taurine as a physiological gliotransmitter and show that gliotransmission is a spatially constrained process that can be modulated by the morphological rearrangement of astrocytes