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The Flexible Array of Radars and Mesonets (FARM) Facility is an extensive mobile/quickly deployable (MQD) multiple-Doppler radar and in situ instrumentation network. The FARM includes four radars: two 3-cm dual polarization, dual frequency (DPDF), Doppler on Wheels (DOW6/DOW7), the Rapid-Scan DOW (RSDOW), and a quickly deployable (QD) DPDF 5-cm C band on Wheels (COW). The FARM includes three mobile mesonet (MM) vehicles with 3.5-m masts, an array of rugged QD weather stations (PODNET), QD weather stations deployed on infrastructure such as light/power poles (POLENET), four disdrometers, six MQD upper-air sounding systems and a Mobile Operations and Repair Center (MORC). The FARM serves a wide variety of research/educational uses. Components have deployed to >30 projects during 1995–2020 in the United States, Europe, and South America, obtaining pioneering observations of a myriad of small spatial- and temporal-scale phenomena including tornadoes, hurricanes, lake-effect snow storms, aircraft-affecting turbulence, convection initiation, microbursts, intense precipitation, boundary layer structures and evolution, airborne hazardous substances, coastal storms, wildfires and wildfire suppression efforts, weather modification effects, and mountain/alpine winds and precipitation. The radars and other FARM systems support innovative educational efforts, deploying >40 times to universities/colleges, providing hands-on access to cutting-edge instrumentation for their students. The FARM provides integrated multiple radar, mesonet, sounding, and related capabilities enabling diverse and robust coordinated sampling of three-dimensional vector winds, precipitation, and thermodynamics increasingly central to a wide range of mesoscale research. Planned innovations include S-band on Wheels Network (SOWNET) and Bistatic Adaptable Radar Network (BARN), offering more qualitative improvements to the field project observational paradigm, providing broad, flexible, and inexpensive 10-cm radar coverage and vector wind field measurements.

The Sawyer PointOne™ household hollow fiber membrane filter (PointOne) efficaciously removes microbiological indicators in the laboratory, and is increasingly considered for emergency response. To our knowledge, PointOne effectiveness in emergencies had not been evaluated. In South Sudan, 773 PointOnes were distributed. For 13 months after distribution, household surveys were completed quarterly, water quality testing was conducted monthly, and post-mortem analysis was completed at study midline to assess acceptability, effectiveness, and membrane fouling, respectively. Recipients found PointOnes acceptable, with high rates of demonstrated correct use (97–100%) and correct backflushing (96–100%). PointOnes effectively reduced thermotolerant coliforms for four months. When surface water use increased, effectiveness dropped, with 38% of filtrate samples contaminated. After backflushing filters with 0.2% chlorine solution, effectiveness improved; however, 5–38% of PointOne filtrate samples remained contaminated over subsequent months. Irreversible fouling was documented during post-mortem analysis. These results highlight that while PointOnes can improve household water quality within an emergency, PointOnes can foul within 4–6 months of use, depending on influent water quality. It is recommended that future PointOne distributions include continuous monitoring and an appropriate cleaning regime, based on influent water quality, to ensure continued performance. Further research on source water quality impacts on PointOne performance is recommended.

Significance This study documents the actual distribution of supercell-tornado wind intensities and sizes, revealing that most are much stronger than damage surveys indicate, with >20% of tornadoes potentially capable of causing catastrophic EF-4/EF-5 damage. Additionally, supercell tornadoes are shown to be much wider than damage surveys indicate. These results are significant for tornado science, tornado risk quantification and mitigation, and design for more resilient communities. We also present meaningful comparisons of the distribution of actually observed tornado intensities and sizes with theoretical predictions, which is significant for basic tornado science., Tornadoes cause damage, injury, and death when intense winds impact structures. Quantifying the strength and extent of such winds is critical to characterizing tornado hazards. Ratings of intensity and size are based nearly entirely on postevent damage surveys [R. Edwards et al., Bull. Am. Meteorol. Soc. 94, 641–653 (2013)]. It has long been suspected that these suffer low bias [C. A. Doswell, D. W. Burgess, Mon. Weather Rev. 116, 495–501 (1988)]. Here, using mapping of low-level tornado winds in 120 tornadoes, we prove that supercell tornadoes are typically much stronger and wider than damage surveys indicate. Our results permit an accurate assessment of the distribution of tornado intensities and sizes and tornado wind hazards, based on actual wind-speed observations, and meaningful comparisons of the distribution of tornado intensities and sizes with theoretical predictions. We analyze data from Doppler On Wheels (DOW) radar measurements of 120 tornadoes at the time of peak measured intensity. In striking contrast to conventional damage-based climatologies, median tornado peak wind speeds are ∼60 m⋅s−1, capable of causing significant, Enhanced Fujita Scale (EF)-2 to -3, damage, and 20% are capable of the most intense EF-4/EF-5 damage. National Weather Service (NWS) EF/wind speed ratings are 1.2 to 1.5 categories (∼20 m⋅s−1) lower than DOW observations for tornadoes documented by both the NWS and DOWs. Median tornado diameter is 250 to 500 m, with 10 to 15% >1 km. Wind engineering tornado-hazard-model predictions and building wind resistance standards may require upward adjustment due to the increased wind-damage risk documented here.

We provide an analysis of innovation at SAP using bibliometric analysis of patents.A rotation and sort procedure was applied to the text.A frequent itemset analysis was performed using the word occurrence matrix.A blockmodeling algorithm was applied to explore relatedness between terms.We integrate text and network analysis tools to perform bibliometric analysis. Easily accessible patent databases and advances in technology have enabled the exploration of organizational innovation through the analysis of patent records. However, the textual content of patents presents obstacles to gleaning useful information. In this study, we develop an expert system framework that utilizes text and data mining procedures for analyzing innovation through textual patent data. Specifically, we use patent titles representing the innovation activity at one company (SAP) and perform a bibliometric analysis using our proposed framework. Enterprise software, of which SAP is a pioneering developer, must serve a wide assortment of functions for companies in many different industries. In addition, SAP's sole focus is on enterprise software and it is a market leader in the category with substantial patent activity over the last decade. Using our framework to analyze SAP's patent activity provides a demonstration of how our bibliometric analysis can summarize and identify trends in innovation in a large software company. Our results illustrate that SAP has a breadth of innovative activity spread over the three-tier software engineering architecture and a lack of topical repetition indicative of limited depth. SAP's innovation is also seen to emphasize data management and quickly integrate emerging technologies. Results of an analysis on any company following our framework could be used for a variety of purposes, including: to examine the scope and scale of innovation of an organization, to examine the influence of technological trends on businesses, or to gain insight into corporate strategy that could be used to aid planning, investment, and purchasing decisions.

Polyvinyl Alcohol (PVA) fiber reinforced mortars (FRM) have been shown to increase the ductility of unreinforced masonry walls thus improving their out-of-plane flexural capacities. As these mortars become increasingly popular, their durability under freeze-thaw conditions requires further scrutiny. Previously, the durability of PVA FRM has been evaluated as mortar components only and not in combination with masonry units. The freeze-thaw testing of masonry mortars requires a complex analysis to duplicate in-situ conditions. Accelerated testing conditions are desired to represent the weathering that a structure would endure over time. This is done by simulating an aggressive weathering pattern on a test specimen in order for the analysis of the durability of the mortar and brick to be obtained within a timely manner. Currently, the standard freeze-thaw durability testing method for cementitious materials utilized in the United States of America, ASTM C666/C666M-03, is characterized by two methods: rapid freezing in water and thawing in water; and rapid freezing in air and thawing in water. This testing method provides a durability rating for specimens created and contained within a laboratory, but does not accurately represent all of the environmental factors that influence the durability of a mortar/brick structure. In this study, in order to replicate in-situ conditions, PVA FRM test specimens are constructed and subjected to freezing in water on only one side and are enclosed in a plastic bag to remedy the effect of the dry, frozen air reducing the moisture content of the mortar. Furthermore, the test specimens are frozen and thawed in a controlled environmental chamber where the relative humidity is controlled to prevent moisture change within the specimen. This enables rapid thawing of the specimen while controlling the relative humidity to better represent the in situ characteristics of masonry structures. The specimens are then subjected to 300 freeze-thaw cycles and evaluated to determine their degradation over that time. Results of the testing show limited reduction in material volume and weight of the PVA FRM compared to control samples that do not include PVA fibers.

GSK207040 (5-[(3-cyclobutyl-2,3,4,5-tetrahydro-1 H -3-benzazepin-7-yl)oxy]- N -methyl-2-pyrazinecarboxamide) and GSK334429 (1-(1-methylethyl)-4-({1-[6-(trifluoromethyl)-3-pyridinyl]-4-piperidinyl}carbonyl)hexahydro-1 H -1,4-diazepine) are novel and selective non-imidazole histamine H 3 receptor antagonists from distinct chemical series with high affinity for human (p K i = 9.67 ± 0.06 and 9.49 ± 0.09, respectively) and rat (p K i = 9.08 ± 0.16 and 9.12 ± 0.14, respectively) H 3 receptors expressed in cerebral cortex. At the human recombinant H 3 receptor, GSK207040 and GSK334429 were potent functional antagonists (pA 2 = 9.26 ± 0.04 and 8.84 ± 0.04, respectively versus H 3 agonist-induced changes in cAMP) and exhibited inverse agonist properties (pIC 50 = 9.20 ± 0.36 and 8.59 ± 0.04 versus basal GTPγS binding). Following oral administration, GSK207040 and GSK334429 potently inhibited cortical ex vivo [ 3 H]- R -α-methylhistamine binding (ED 50 = 0.03 and 0.35 mg/kg, respectively). Functional antagonism of central H 3 receptors was demonstrated by blockade of R -α-methylhistamine-induced dipsogenia in rats (ID 50 = 0.02 and 0.11 mg/kg p.o. for GSK207040 and GSK334429, respectively). In more pathophysiologically relevant pharmacodynamic models, GSK207040 (0.1, 0.3, 1 and 3 mg/kg p.o.) and GSK334429 (0.3, 1 and 3 mg/kg p.o.) significantly reversed amnesia induced by the cholinergic antagonist scopolamine in a passive avoidance paradigm. In addition, GSK207040 (0.1, 0.3 and 1 mg/kg p.o.) and GSK334429 (3 and 10 mg/kg p.o.) significantly reversed capsaicin-induced reductions in paw withdrawal threshold, suggesting for the first time that blockade of H 3 receptors may be able to reduce tactile allodynia. Novel H 3 receptor antagonists such as GSK207040 and GSK334429 may therefore have therapeutic potential not only in dementia but also in neuropathic pain.

This Letter describes the discovery of a novel series of H3 receptor antagonists. The initial medicinal chemistry strategy focused on deconstructing and simplifying an early screening hit which rapidly led to the discovery of a novel series of H3 receptor antagonists based on the benzazepine core. Employing an H3 driven pharmacodynamic model, the series was then further optimised through to a lead compound that showed robust in vivo functional activity and possessed overall excellent developability properties.

A method is described for computerized measurement of blood pressure (BP) in small animals. As described, the system measures BP in up to four experimental animals at one time by sequential sampling but can be expanded to take data from up to 10. It requires an Apple II computer, and is run from a Grass pen-recording system. Pulse rate and systolic and diastolic BP are measured, and these variables are used to calculate mean arterial pressure (MAP) and the time integral of MAP minute by minute. The data are displayed in real time and stored hourly on floppy disc for further analysis.

Background Laboratory services have a central role in supporting screening, diagnosis, and management of patients. The increase in chronic disease management in primary care for conditions such as diabetes mellitus requires regular monitoring of patients' biochemical parameters. This process offers a route for improving the quality of care that patients receive by using test results as a vehicle for delivering educational messages as well as the test result itself. Aim To develop and evaluate the effectiveness of a quality improvement initiative to improve the care of patients with diabetes using test report reminders. Design A programme of four cluster randomised controlled trials within one population of general practices. Participants General practices in Newcastle-upon-Tyne, UK. Intervention Brief educational messages added to paper and electronic general practice laboratory test reports introduced over two phases. Phase One messages, attached to Haemoglobin A1c (HbA1c) reports, targeted glycaemic and cholesterol control. Phase Two messages, attached to albumin:creatinine ratio (ACR) reports, targeted blood pressure (BP) control and foot inspection. Outcomes General practice mean levels of HbA1c and cholesterol (Phase One) and diastolic and systolic BP and proportions of patients having undergone foot inspections (Phase Two); number of tests requested. Trial registration Current Controlled Trial ISRCTN2186314.

6-[(3-Cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-N-methyl-3-pyridinecarboxamide hydrochloride (GSK189254) is a novel histamine H(3) receptor antagonist with high affinity for human (pK(i) = 9.59 -9.90) and rat (pK(i) = 8.51-9.17) H(3) receptors. GSK189254 is >10,000-fold selective for human H(3) receptors versus other targets tested, and it exhibited potent functional antagonism (pA(2) = 9.06 versus agonist-induced changes in cAMP) and inverse agonism [pIC(50) = 8.20 versus basal guanosine 5'-O-(3-[(35)S]thio)triphosphate binding] at the human recombinant H(3) receptor. In vitro autoradiography demonstrated specific [(3)H]GSK189254 binding in rat and human brain areas, including cortex and hippocampus. In addition, dense H(3) binding was detected in medial temporal cortex samples from severe cases of Alzheimer's disease, suggesting for the first time that H(3) receptors are preserved in late-stage disease. After oral administration, GSK189254 inhibited cortical ex vivo R-(-)-alpha-methyl[imidazole-2,5(n)-(3)H]histamine dihydrochloride ([(3)H]R-alpha-methylhistamine) binding (ED(50) = 0.17 mg/kg) and increased c-Fos immunoreactivity in prefrontal and somatosensory cortex (3 mg/kg). Microdialysis studies demonstrated that GSK189254 (0.3-3 mg/kg p.o.) increased the release of acetylcholine, noradrenaline, and dopamine in the anterior cingulate cortex and acetylcholine in the dorsal hippocampus. Functional antagonism of central H(3) receptors was demonstrated by blockade of R-alpha-methylhistamine-induced dipsogenia in rats (ID(50) = 0.03 mg/kg p.o.). GSK189254 significantly improved performance of rats in diverse cognition paradigms, including passive avoidance (1 and 3 mg/kg p.o.), water maze (1 and 3 mg/kg p.o.), object recognition (0.3 and 1 mg/kg p.o.), and attentional set shift (1 mg/kg p.o.). These data suggest that GSK189254 may have therapeutic potential for the symptomatic treatment of dementia in Alzheimer's disease and other cognitive disorders.