Sustainability indicator for the prevention of potential thermal interferences between groundwater heat pump systems in urban aquifers

The steady increase of geothermal systems using groundwater is compromising the renewability of the geothermal resources in shallow urban aquifers. To ensure sustainability, scientifically-based criteria are required to prevent potential thermal interferences between geothermal systems. In this work, a management indicator (balanced sustainability index, BSI) applicable to groundwater heat pump systems is defined to assign a quantitative value of sustainability to each system, based on their intrinsic potential to produce thermal interference. The BSI indicator relies on the net heat balance transferred to the terrain throughout the year and the maximum seasonal thermal load associated. To define this indicator, 75 heating-cooling scenarios based in 23 real systems were established to cover all possible different operational conditions. The scenarios were simulated in a standard numerical model, adopted as a reference framework, and thermal impacts were evaluated. Two polynomial regression models were used for the interpolation of thermal impacts, thus allowing the direct calculation of the sustainability indicator developed as a function of heating-cooling ratios and maximum seasonal thermal loads. The BSI indicator could provide authorities and technicians with scientifically-based criteria to establish geothermal monitoring programs, which are critical to maintain the implementation rates and renewability of these systems in the cities

Third-Line Nivolumab Monotherapy in Recurrent Small Cell Lung Cancer : CheckMate 032

Introduction: For patients with recurrent SCLC, topotecan remains the only approved second-line treatment, and the outcomes are poor. CheckMate 032 is a phase 1/2, multicenter, open-label study of nivolumab or nivolumab plus ipilimumab in SCLC or other advanced/metastatic solid tumors previously treated with one or more platinum-based chemotherapies. We report results of third- or later-line nivolumab monotherapy treatment in SCLC. Methods: In this analysis, patients with limited-stage or extensive-stage SCLC and disease progression after two or more chemotherapy regimens received nivolumab monotherapy, 3 mg/kg every 2 weeks, until disease progression or unacceptable toxicity. The primary end point was objective response rate. Secondary end points included duration of response, progression-free survival, overall survival, and safety. Results: Between December 4, 2013, and November 30, 2016, 109 patients began receiving third- or later-line nivolumab monotherapy. At a median follow-up of 28.3 months (from first dose to database lock), the objective response rate was 11.9% (95% confidence interval: 6.5\u201319.5) with a median duration of response of 17.9 months (range 3.0\u201342.1). At 6 months, 17.2% of patients were progression-free. The 12-month and 18-month overall survival rates were 28.3% and 20.0%, respectively. Grade 3 to 4 treatment-related adverse events occurred in 11.9% of patients. Three patients (2.8%) discontinued because of treatment-related adverse events. Conclusions: Nivolumab monotherapy provided durable responses and was well tolerated as a third- or later-line treatment for recurrent SCLC. These results suggest that nivolumab monotherapy is an effective third- or later-line treatment for this patient population

Observation of the Crab Nebula with the HAWC Gamma-Ray Observatory

The Crab Nebula is the brightest TeV gamma-ray source in the sky and has been used for the past 25 years as a reference source in TeV astronomy, for calibration and verification of new TeV instruments. The High Altitude Water Cherenkov Observatory (HAWC), completed in early 2015, has been used to observe the Crab Nebula at high significance across nearly the full spectrum of energies to which HAWC is sensitive. HAWC is unique for its wide field-of-view, nearly 2 sr at any instant, and its high-energy reach, up to 100 TeV. HAWC's sensitivity improves with the gamma-ray energy. Above $\sim$1 TeV the sensitivity is driven by the best background rejection and angular resolution ever achieved for a wide-field ground array. We present a time-integrated analysis of the Crab using 507 live days of HAWC data from 2014 November to 2016 June. The spectrum of the Crab is fit to a function of the form $\phi(E) = \phi_0 (E/E_{0})^{-\alpha -\beta\cdot{\rm{ln}}(E/E_{0})}$. The data is well-fit with values of $\alpha=2.63\pm0.03$, $\beta=0.15\pm0.03$, and log$_{10}(\phi_0~{\rm{cm}^2}~{\rm{s}}~{\rm{TeV}})=-12.60\pm0.02$ when $E_{0}$ is fixed at 7 TeV and the fit applies between 1 and 37 TeV. Study of the systematic errors in this HAWC measurement is discussed and estimated to be $\pm$50\% in the photon flux between 1 and 37 TeV. Confirmation of the Crab flux serves to establish the HAWC instrument's sensitivity for surveys of the sky. The HAWC survey will exceed sensitivity of current-generation observatories and open a new view of 2/3 of the sky above 10 TeV.Comment: Submitted 2017/01/06 to the Astrophysical Journa

Secreted Bacterial Effectors and Host-Produced Eiger/TNF Drive Death in a Salmonella-Infected Fruit Fly

Death by infection is often as much due to the host's reaction as it is to the direct result of microbial action. Here we identify genes in both the host and microbe that are involved in the pathogenesis of infection and disease in Drosophila melanogaster challenged with Salmonella enterica serovartyphimurium (S. typhimurium). We demonstrate that wild-type S. typhimurium causes a lethal systemic infection when injected into the hemocoel of D. melanogaster. Deletion of the gene encoding the secreted bacterial effector Salmonella leucine-rich (PslrP) changes an acute and lethal infection to one that is persistent and less deadly. We propose a model in which Salmonella secreted effectors stimulate the fly and thus cause an immune response that is damaging both to the bacteria and, subsequently, to the host. In support of this model, we show that mutations in the fly gene eiger, a TNF homolog, delay the lethality of Salmonella infection. These results suggest that S. typhimurium-infected flies die from a condition that resembles TNF-induced metabolic collapse in vertebrates. This idea provides us with a new model to study shock-like biology in a genetically manipulable host. In addition, it allows us to study the difference in pathways followed by a microbe when producing an acute or persistent infection

The 2HWC HAWC Observatory Gamma Ray Catalog

We present the first catalog of TeV gamma-ray sources realized with the recently completed High Altitude Water Cherenkov Observatory (HAWC). It is the most sensitive wide field-of-view TeV telescope currently in operation, with a 1-year survey sensitivity of ~5-10% of the flux of the Crab Nebula. With an instantaneous field of view >1.5 sr and >90% duty cycle, it continuously surveys and monitors the sky for gamma ray energies between hundreds GeV and tens of TeV. HAWC is located in Mexico at a latitude of 19 degree North and was completed in March 2015. Here, we present the 2HWC catalog, which is the result of the first source search realized with the complete HAWC detector. Realized with 507 days of data and represents the most sensitive TeV survey to date for such a large fraction of the sky. A total of 39 sources were detected, with an expected contamination of 0.5 due to background fluctuation. Out of these sources, 16 are more than one degree away from any previously reported TeV source. The source list, including the position measurement, spectrum measurement, and uncertainties, is reported. Seven of the detected sources may be associated with pulsar wind nebulae, two with supernova remnants, two with blazars, and the remaining 23 have no firm identification yet.Comment: Submitted 2017/02/09 to the Astrophysical Journa

Daily monitoring of TeV gamma-ray emission from Mrk 421, Mrk 501, and the Crab Nebula with HAWC

We present results from daily monitoring of gamma rays in the energy range $\sim0.5$ to $\sim100$ TeV with the first 17 months of data from the High Altitude Water Cherenkov (HAWC) Observatory. Its wide field of view of 2 steradians and duty cycle of $>95$% are unique features compared to other TeV observatories that allow us to observe every source that transits over HAWC for up to $\sim6$ hours each sidereal day. This regular sampling yields unprecedented light curves from unbiased measurements that are independent of seasons or weather conditions. For the Crab Nebula as a reference source we find no variability in the TeV band. Our main focus is the study of the TeV blazars Markarian (Mrk) 421 and Mrk 501. A spectral fit for Mrk 421 yields a power law index $\Gamma=2.21 \pm0.14_{\mathrm{stat}}\pm0.20_{\mathrm{sys}}$ and an exponential cut-off $E_0=5.4 \pm 1.1_{\mathrm{stat}}\pm 1.0_{\mathrm{sys}}$ TeV. For Mrk 501, we find an index $\Gamma=1.60\pm 0.30_{\mathrm{stat}} \pm 0.20_{\mathrm{sys}}$ and exponential cut-off $E_0=5.7\pm 1.6_{\mathrm{stat}} \pm 1.0_{\mathrm{sys}}$ TeV. The light curves for both sources show clear variability and a Bayesian analysis is applied to identify changes between flux states. The highest per-transit fluxes observed from Mrk 421 exceed the Crab Nebula flux by a factor of approximately five. For Mrk 501, several transits show fluxes in excess of three times the Crab Nebula flux. In a comparison to lower energy gamma-ray and X-ray monitoring data with comparable sampling we cannot identify clear counterparts for the most significant flaring features observed by HAWC.Comment: 18 pages, 10 figures, accepted for publication in The Astrophysical Journa

All-particle cosmic ray energy spectrum measured by the HAWC experiment from 10 to 500 TeV

We report on the measurement of the all-particle cosmic ray energy spectrum with the High Altitude Water Cherenkov (HAWC) Observatory in the energy range 10 to 500 TeV. HAWC is a ground based air-shower array deployed on the slopes of Volcan Sierra Negra in the state of Puebla, Mexico, and is sensitive to gamma rays and cosmic rays at TeV energies. The data used in this work were taken from 234 days between June 2016 to February 2017. The primary cosmic-ray energy is determined with a maximum likelihood approach using the particle density as a function of distance to the shower core. Introducing quality cuts to isolate events with shower cores landing on the array, the reconstructed energy distribution is unfolded iteratively. The measured all-particle spectrum is consistent with a broken power law with an index of $-2.49\pm0.01$ prior to a break at $(45.7\pm0.1$) TeV, followed by an index of $-2.71\pm0.01$. The spectrum also respresents a single measurement that spans the energy range between direct detection and ground based experiments. As a verification of the detector response, the energy scale and angular resolution are validated by observation of the cosmic ray Moon shadow's dependence on energy.Comment: 16 pages, 11 figures, 4 tables, submission to Physical Review