Imprecise probabilistic evaluation of sewer flooding in urban drainage systems using random set theory

publication-status: Publishedtypes: ArticleCopyright © 2011 American Geophysical UnionUncertainty analysis is widely applied in water system modeling to quantify prediction uncertainty from models and data. Conventional methods typically handle various kinds of uncertainty using a single characterizing approach, be it probability theory or fuzzy set theory. However, using a single approach may not be appropriate, particularly when uncertainties are of different types. For example, in sewer flood estimation problems, random rainfall variables are used as model inputs and imprecise or subjective information is used to define model parameters. This paper presents a general framework for sewer flood estimation that enables simultaneous consideration of two types of uncertainty: randomness from rainfall data represented using imprecise probabilities and imprecision from model parameters represented by fuzzy numbers. These two types of uncertainties are combined using random set theory and then propagated through a hydrodynamic urban drainage model. Two propagation methods, i.e., discretization and Monte Carlo based methods, are presented and compared, with the latter shown to be much more computationally efficient and hence recommended for high-dimensional problems. The model output (flood depth) is generated in the form of lower and upper cumulative probabilities, which are best estimates given the various stochastic and epistemic uncertainties considered and which embrace the unknown true cumulative probability. The distance between the cumulative probabilities represents the extent of imprecise, incomplete, or conflicting information and can be reduced only when more knowledge is available. The proposed methodology has a more complete and thus more accurate representation of uncertainty in data and models and can effectively handle different uncertainty characterizations in a single, integrated framework for sewer flood estimation

KSR2 mutations are associated with obesity, insulin resistance, and impaired cellular fuel oxidation.

Kinase suppressor of Ras 2 (KSR2) is an intracellular scaffolding protein involved in multiple signaling pathways. Targeted deletion of Ksr2 leads to obesity in mice, suggesting a role in energy homeostasis. We explored the role of KSR2 in humans by sequencing 2,101 individuals with severe early-onset obesity and 1,536 controls. We identified multiple rare variants in KSR2 that disrupt signaling through the Raf-MEKERK pathway and impair cellular fatty acid oxidation and glucose oxidation in transfected cells; effects that can be ameliorated by the commonly prescribed antidiabetic drug, metformin. Mutation carriers exhibit hyperphagia in childhood, low heart rate, reduced basal metabolic rate and severe insulin resistance. These data establish KSR2 as an important regulator of energy intake, energy expenditure, and substrate utilization in humans. Modulation of KSR2-mediated effects may represent a novel therapeutic strategy for obesity and type 2 diabetes.This work was supported by the Wellcome Trust (098497/Z/12/Z; 077016/Z/05/Z; 096106/Z/11/Z) (ISF and LRP), Medical Research Council (MC_U106179471) (NW), NIHR Cambridge Biomedical Research Centre (ISF, IB and SOR), and European Research Council (ISF). This study makes use of data generated by the UK10K Consortium (WT091310). A full list of the investigators who contributed to the generation of the data is available from http://www.UK10K.org.This is the final published version. It first appeared at http://www.cell.com/abstract/S0092-8674%2813%2901276-2

The expression of nuclear and membrane estrogen receptors in the European eel throughout spermatogenesis

[EN] Estradiol (E-2) can bind to nuclear estrogen receptors (ESR) or membrane estrogen receptors (GPER). While mammals possess two nuclear ESRs and one membrane GPER, the European eel, like most other teleosts, has three nuclear ESRs and two membrane GPERs, as the result of a teleost specific genome duplication. In the current study, the expression of the three nuclear ESRs (ESR1, ESR2a and ESR2b) and the two membrane GPERs (GPERa and GPERb) in the brain-pituitary-gonad (BPG) axis of the European eel was measured, throughout spermatogenesis. The eels were first transferred from freshwater (FW) to seawater (SW), inducing parallel increases in E2 plasma levels and the expression of ESRs. This indicates that salinity has a stimulatory effect on the E-2 signalling pathway along the BPG axis. Stimulation of sexual maturation by weekly injections of human chorionic gonadotropin (hCG) induced a progressive decrease in E-2 plasma levels, and different patterns of expression of ESRs and GPERs in the BPG axis. The expression of nuclear ESRs increased in some parts of the brain, suggesting a possible upregulation due to a local production of E-2. In the testis, the highest expression levels of the nuclear ESRs were observed at the beginning of spermatogenesis, possibly mediating the role of E2 as spermatogonia renewal factor, followed by a sharply decrease in the expression of ESRs. Conversely, there was a marked increase observed in the expression of both membrane GPERs throughout spermatogenesis, suggesting they play a major role in the final stages of spermatogenesis.Funded by the Spanish Ministry of Science and Innovation (REPRO-TEMP project; AGL2013-41646-R) and IMPRESS (Marie Sklodowska-Curie Actions; Grant agreement no: 642893). M.C. Vilchez has a predoctoral grant from UPV PAID Programme (2011-S2-02-6521), M. Morini has a predoctoral grant from Generalitat Valenciana (Programa Grisolia). D.S. Penaranda was supported by MICINN and UPV (PTA2011-4948-1).Morini, M.; Peñaranda, D.; Vilchez Olivencia, MC.; Tveiten, H.; Lafont, A.; Dufour, S.; Pérez Igualada, LM.... (2017). The expression of nuclear and membrane estrogen receptors in the European eel throughout spermatogenesis. Comparative Biochemistry and Physiology Part A Molecular & Integrative Physiology. 203:91-99. doi:10.1016/j.cbpa.2016.08.020S919920

Combined Treatment of Heterocyclic Analogues and Benznidazole upon Trypanosoma cruzi In Vivo

Chagas disease caused by Trypanosoma cruzi is an important cause of mortality and morbidity in Latin America but no vaccines or safe chemotherapeutic agents are available. Combined therapy is envisioned as an ideal approach since it may enhance efficacy by acting upon different cellular targets, may reduce toxicity and minimize the risk of drug resistance. Therefore, we investigated the activity of benznidazole (Bz) in combination with the diamidine prodrug DB289 and in combination with the arylimidamide DB766 upon T. cruzi infection in vivo. The oral treatment of T.cruzi-infected mice with DB289 and Benznidazole (Bz) alone reduced the number of circulating parasites compared with untreated mice by about 70% and 90%, respectively. However, the combination of these two compounds decreased the parasitemia by 99% and protected against animal mortality by 100%, but without providing a parasitological cure. When Bz (p.o) was combined with DB766 (via ip route), at least a 99.5% decrease in parasitemia levels was observed. DB766+Bz also provided 100% protection against mice mortality while Bz alone provided about 87% protection. This combined therapy also reduced the tissular lesions induced by T. cruzi infection: Bz alone reduced GPT and CK plasma levels by about 12% and 78% compared to untreated mice group, the combination of Bz with DB766 resulted in a reduction of GPT and CK plasma levels of 56% and 91%. Cure assessment through hemocultive and PCR approaches showed that Bz did not provide a parasitological cure, however, DB766 alone or associated with Bz cured ≥13% of surviving animals

A Noninvasive Intratracheal Inoculation Method for the Study of Pulmonary Melioidosis

Pulmonary melioidosis, a disease manifestation caused by the bacterium Burkholderia pseudomallei, has been studied using aerosols or intranasal inoculation in small animal models. Both have inherent disadvantages which may not accurately model primary pulmonary melioidosis in humans. Intratracheal inoculation by direct visualization of the tracheal opening offers an alternative technique for infection that overcomes the disadvantages of aerosol and intranasal challenge. In this study, we describe a method which requires relatively inexpensive equipment, little training, and is compliant with the operational constraints of a BSL3 laboratory. Results obtained using trypan demonstrated that an inoculum can be accurately delivered into the lungs of mice within a biosafety cabinet. Whole body imaging and histopathology confirmed that mice inoculated intratracheally with B. pseudomallei develop the primary focus of infection in the lungs, and not the nasal passages which can lead to invasion of the central nervous system and potential neurologic complications. Further, based on colony counts and bioluminescent imaging, dissemination to secondary organs occurred as expected. Taken together, this intratracheal method of inoculation fulfills four goals: (1) to accurately deliver B. pseudomallei into the lungs of the animal model, (2) to avoid potentially confounding complications due to primary infections at sites other than the lung, (3) to maintain normal organ dissemination, and (4) to be BSL3 compliant

VIBRATIONAL POPULATION DISTRIBUTIONS OF THE GROUND STATE OF BARIUM OXIDE

Author Institution: Quantum Institute, University of CaliforniaThe vibrational population distributions of ground state BaO formed by the reactions $Ba + O_{2}$ and $Ba + N_{2}O$ at 0.3 to 10 Torr have been measured. A scanning rhodamine 6G cw dye laser is used to pump $X^{1}\Sigma(\nu^{\prime\prime}) \rightarrow A^{1}\Sigma(\nu ^{\prime})$ transitions from sequential ground state vibrationa1 levels $(\nu^{\prime\prime}_{i})$, while a 3 nm resolution monochromator detects only the photo-luminescence originating from this $A^{1}\Sigma(\nu ^{\prime})$ in a band outside the dye laser region. Shown below are the relative populations, determined from laser induced fluorescence intensities, of the $\nu ^{\prime} = 0$ through $\nu ^{\prime} = 7$ vibrational levels of $BaO X^{1}\Sigma$ formed in the $Ba + 0_{2}$ reaction at 0.3 Torr. [FIGURE] Similar data for the $Ba + N_{2}O$ reaction suggest that a population inversion may exist between $BaO\ \ A^{1}\Sigma(\nu^{\prime} = 1)^{1}$ and $X^{1}\Sigma(\nu^{\prime\prime}= 7)$ at 16 Torr

The Impact of Primary Immunization Route on the Outcome of Infection With SARS-Cov-2 in a Hamster Model of COVID-19

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has resulted in over 6.7 million deaths worldwide. COVID-19 vaccines administered parenterally via intramuscular or subcutaneous (SC) routes have reduced the severity of respiratory infections, hospitalization rates, and overall mortality. However, there is a growing interest in developing mucosally delivered vaccines to further enhance the ease and durability of vaccination. This study compared the immune response in hamsters immunized with live SARS-CoV-2 virus via SC or intranasal (IN) routes and assessed the outcome of a subsequent IN SARS-CoV-2 challenge. Results showed that SC-immunized hamsters elicited a dose-dependent neutralizing antibody response but of a significantly lower magnitude than that observed in IN-immunized hamsters. The IN challenge with SARS-CoV-2 in SC-immunized hamsters resulted in body weight loss, increased viral load, and lung pathology than that observed in IN-immunized and IN-challenged counterparts. These results demonstrate that while SC immunization renders some degree of protection, IN immunization induces a stronger immune response and better protection against respiratory SARS-CoV-2 infection. Overall, this study provides evidence that the route of primary immunization plays a critical role in determining the severity of a subsequent respiratory infection caused by SARS-CoV-2. Furthermore, the findings suggest that IN route of immunization may be a more effective option for COVID-19 vaccines than the currently used parenteral routes. Understanding the immune response to SARS-CoV-2 elicited via different immunization routes may help guide more effective and long-lasting vaccination strategies