•Hydro-climatic uncertainties must be considered in reservoir operations.•Quantifying uncertain multi-sector tradeoffs poses computational barriers.•Monte Carlo sampling impacts mathematical and ...computational difficulty.•Parallel auto-adaptive co-evolutionary search helps overcome challenges.•Results are for the six-objective Lower Susquehanna benchmarking test case.
Reservoir operations are central to our ability to manage river basin systems serving conflicting multi-sectoral demands under increasingly uncertain futures. These challenges motivate the need for new solution strategies capable of effectively and efficiently discovering the multi-sectoral tradeoffs that are inherent to alternative reservoir operation policies. Evolutionary many-objective direct policy search (EMODPS) is gaining importance in this context due to its capability of addressing multiple objectives and its flexibility in incorporating multiple sources of uncertainties. This simulation-optimization framework has high potential for addressing the complexities of water resources management, and it can benefit from current advances in parallel computing and meta-heuristics. This study contributes a diagnostic assessment of state-of-the-art parallel strategies for the auto-adaptive Borg Multi Objective Evolutionary Algorithm (MOEA) to support EMODPS. Our analysis focuses on the Lower Susquehanna River Basin (LSRB) system where multiple sectoral demands from hydropower production, urban water supply, recreation and environmental flows need to be balanced. Using EMODPS with different parallel configurations of the Borg MOEA, we optimize operating policies over different size ensembles of synthetic streamflows and evaporation rates. As we increase the ensemble size, we increase the statistical fidelity of our objective function evaluations at the cost of higher computational demands. This study demonstrates how to overcome the mathematical and computational barriers associated with capturing uncertainties in stochastic multiobjective reservoir control optimization, where parallel algorithmic search serves to reduce the wall-clock time in discovering high quality representations of key operational tradeoffs. Our results show that emerging self-adaptive parallelization schemes exploiting cooperative search populations are crucial. Such strategies provide a promising new set of tools for effectively balancing exploration, uncertainty, and computational demands when using EMODPS.
Multireservoir systems are designed to serve multiple conflicting demands over varying time scales that may be out of phase with the system's hydroclimatic inputs. Adaptive, nonlinear reservoir ...control policies are often best suited to serve these needs. However, nonlinear operating policies are hard to interpret, so water managers tend to favor simple, static rules that may not effectively manage conflicts between the system's multisectoral demands. In this study, we introduce an analytical framework for opening the black box of optimized nonlinear operating policies, decomposing their time‐varying information sensitivities to show how their adaptive and coordinated release prescriptions better manage hydrologic variability. Interestingly, these information sensitivities vary significantly across policies depending on how they negotiate tradeoffs between conflicting objectives. We illustrate this analysis in the Red River basin of Vietnam, where four major reservoirs serve to protect the capital of Hanoi from flooding while also providing the surrounding region with electric power and meeting multisectoral water demands for the agricultural and urban economies. Utilizing Evolutionary Multi‐Objective Direct Policy Search, we are able to design policies that, using the same information as sequential if/then/else‐based operating guidelines developed by the government, outperform these traditional rules with respect to every objective. Policy diagnostics using time‐varying sensitivity analysis illustrate how the Evolutionary Multi‐Objective Direct Policy Search operations better adapt and coordinate information use to reduce food‐energy‐water conflicts in the basin. These findings accentuate the benefits of transitioning to dynamic operating policies in order to manage evolving hydroclimatic variability and socioeconomic demands in multipurpose reservoir networks.
Key Points
We contribute an analytical framework for understanding the time‐varying information sensitivities of multireservoir operating policies
We find that adaptive and coordinated information use by optimized nonlinear operating policies yields superior multiobjective performance
These time‐varying information sensitivities can change significantly across policies depending on how they balance conflicting objectives
Multireservoir systems require robust and adaptive control policies capable of managing hydroclimatic variability and human demands across a range of time scales. This is especially true for river ...basins with high intraannual and interannual variability, such as monsoonal systems that need to buffer against seasonal droughts while also managing extreme floods. Moreover, the timing, intensity, duration, and frequency of these hydrologic extremes may evolve with deeply uncertain changes in socioeconomic and climatic pressures. This study contributes an innovative method for exploring how possible changes in the timing and magnitude of the monsoonal cycle impact the robustness of reservoir operating policies designed assuming stationary hydrologic and socioeconomic conditions. We illustrate this analysis on the Red River basin in Vietnam, where reservoirs and dams serve as important sources of hydropower production, multisectoral water supply, and flood protection for the capital city of Hanoi. Applying our scenario discovery approach, we find that reservoir operations designed assuming stationarity provide robust hydropower performance in the Red River but that increased mean streamflow, amplification of the within‐year monsoonal cycle, and increased interannual variability all threaten their ability to manage flood risk. Additionally, increased agricultural water demands can only be tolerated if they are accompanied by greater mean flow, exacerbating food‐flood trade‐offs in the basin. These findings highlight the importance of exploring the impacts of a wide range of deeply uncertain socioeconomic and hydrologic factors when evaluating system robustness in monsoonal river basins, considering in particular both lower‐order moments of annual streamflow and intraannual monsoonal behavior.
Key Points
A new synthetic streamflow rescaling method for scenario discovery is introduced
The method discovers flood risks caused by multiple mechanisms beyond mean hydrologic changes
Multisectoral trade‐offs are exacerbated by strengthening monsoon and greater interannual variability
We report the synthesis and crystal structure of a new high-temperature form of Ca3P2. The crystal structure was determined through Rietveld refinements of synchrotron powder x-ray diffraction data. ...This form of Ca3P2 has a crystal structure of the hexagonal Mn5Si3 type, with a Ca ion deficiency compared to the ideal 5:3 stoichiometry. This yields a stable, charge-balanced compound of Ca2+ and P3−. We also report the observation of a secondary hydride phase, Ca5P3H, which again is a charge-balanced compound. The calculated band structure of Ca3P2 indicates that it is a three-dimensional Dirac semimetal with a highly unusual ring of Dirac nodes at the Fermi level. The Dirac states are protected against gap opening by a mirror plane in a manner analogous to what is seen for graphene.
Chemotherapy has been explored as a treatment option for metastatic prostate cancer since the early 1980s. Docetaxel, a taxane chemotherapeutic, was approved for the treatment of men with metastatic ...castration-resistant prostate cancer in 2004, and is now standard of care for late stage disease. Recent clinical studies demonstrated that patients with metastatic castration-sensitive disease, and possibly those with high-risk localized prostate cancer also benefit from docetaxel administration, expanding the role of chemotherapy in the prostate cancer treatment landscape. Another taxane, cabazitaxel, is approved for post-docetaxel metastatic castration-resistant prostate cancer. Taxanes and other chemotherapeutics, such as carboplatin, are now being tested in combination regimens. This review presents an outline of recent and ongoing clinical studies assessing docetaxel and its derivative cabazitaxel at different stages of the disease, and in various combinations with other agents. We summarize current knowledge on biomarkers predictive of response to chemotherapy, which may in future be used to guide individualized treatment decisions.
Background: Individual differences in subjective response to alcohol, as measured by laboratory‐based alcohol challenge, have been identified as a candidate phenotypic risk factor for the ...development of alcohol‐use disorders (AUDs). Two models have been developed to explain the role of subjective response to alcohol, but predictions from the 2 models are contradictory, and theoretical consensus is lacking.
Methods: This investigation used a meta‐analytic approach to review the accumulated evidence from alcohol‐challenge studies of subjective response as a risk factor. Data from 32 independent samples (total N = 1,314) were aggregated to produce quantitative estimates of the effects of risk‐group status (i.e., positive family history of AUDs or heavier alcohol consumption) on subjective response.
Results: As predicted by the Low Level of Response Model (LLRM), family history–positive groups experienced reduced overall subjective response relative to family history–negative groups. This effect was most evident among men, with family history–positive men responding more than half a standard deviation less than family history–negative men. In contrast, consistent with the Differentiator Model (DM), heavier drinkers of both genders responded 0.4 standard deviations less on measures of sedation than did the lighter drinkers but nearly half a standard deviation more on measures of stimulation, with the stimulation difference appearing most prominent on the ascending limb of the blood alcohol concentration curve.
Conclusions: The accumulated results from 3 decades of family history comparisons provide considerable support for the LLRM. In contrast, results from typical consumption comparisons were largely consistent with predictions of the DM. The LLRM and DM may describe 2 distinct sets of phenotypic risk, with importantly different etiologies and predictions for the development of AUDs.
Abstract Objectives Presentation of a methodological approach using stereo and scanning electron microscope examination for the failure analysis of an alumina all-ceramic premolar crown (Procera® ...AllCeram). Methods The recovered part of a fractured Procera alumina crown was examined utilizing first a stereomicroscope and second a scanning electron microscope (SEM). The stereomicroscope analysis was performed at low magnifications with oblique lighting in order to enhance spatial relationships and gross detection of crack features. A preliminary fracture surface map of the stereo observations was drawn and used as a guide for the SEM analysis that followed. Specific sites of interest identified under the stereo microscope were analyzed using the SEM at high magnifications searching for small fracture features such as wake hackle and twist hackle within the veneering ceramic in order to confirm the direction of crack propagation. Results At low magnifications and oblique illumination, the stereomicroscope analysis provided an excellent overview of the fractured topography, showing sites of major interest such as a primary edge chip at a margin, a compression curl indicating the end of the fracture event as well as larger hackle lines distributed over the cracked surface. The greater magnifications with the SEM analysis of the sites of interest showed the presence of wake and twist hackle, indicators of the crack propagation direction. A general map of the fracture events could be reconstructed starting with a primary veneer edge chip at the mesial margin. Hackle and wake hackle of the crack front emanating from this margin arose from hoop stresses and propagated through the full crown thickness towards the distal end of the restoration where the compression curl was located. Additional occlusal surface damage in the form of veneer chipping containing arrest lines and twist hackle running in the opposite direction as the main crack path were observed, but occurred as a secondary event without penetrating the alumina core material. Significance Stereo and scanning electron microscopy are complementary analysis techniques useful for the mapping and interpretation of the fracture surface. This case examination is intended to guide the clinical researcher in using qualitative (descriptive) fractography as a tool for understanding the failure process in brittle restorative materials, as well as for assessing possible design inadequacies.
•Shake table tests were performed on a large-scale model building equipped with NES devices.•Experimental results demonstrate that effective mitigation of seismic responses was achieved.•A numerical ...model was developed and two suites of ground motions were selected.•Numerical simulation results demonstrate effectiveness and robustness of NES devices.
As a novel dynamic vibration absorber, the nonlinear energy sink has been studied for mitigating structural and mechanical vibration through the last decade. This paper presents a series of large-scale experimental evaluations and numerical simulations on a system of nonlinear energy sink (NES) devices for mitigating seismic structural responses. Two distinct types of NES devices were installed in the top two floors of a large-scale model building structure. In the device system, four Type I NESs employing smooth essentially nonlinear restoring forces were used in conjunction with two single-sided vibro-impact (SSVI) NESs employing non-smooth impact nonlinearities. These NES devices utilize the existing structural mass and space of the model building to realize an integrated design of building structure with non-parasitic control devices. Scaled historic earthquake ground motions were implemented by a large-scale shake table as the base excitation input into the system. Direct comparisons between mitigated and unmitigated structural responses, including story displacement, column strain and base shear force, demonstrate that rapid mitigation of structural responses was achieved by the system of devices. Reductions of both peak and average values of structural responses were clearly observed. The synergistic effects obtained by simultaneously using two types of NES devices were demonstrated. To computationally investigate the mitigation performance of the devices subjected to a wide variety of ground motions, a numerical model was developed for the structure-NES system and two suites of earthquake ground motions representing distinct earthquake intensities were employed. Simulation results demonstrate that mitigation of structural responses caused by diverse earthquake ground motions can be achieved by a system of NES devices.
The polysaccharide capsule is an essential virulence factor for
in both community-acquired hypervirulent strains as well as health care-associated classical strains that are posing significant ...challenges due to multidrug resistance. Capsule production is known to be transcriptionally regulated by a number of proteins, but very little is known about how these proteins collectively control capsule production. RmpA and RcsB are two known regulators of capsule gene expression, and RmpA is required for the hypermucoviscous (HMV) phenotype in hypervirulent
strains. In this report, we confirmed that these regulators performed their anticipated functions in the ATCC 43816 derivative, KPPR1S:
and
mutants are HMV negative and have reduced capsule gene expression. We also identified a novel transcriptional regulator, RmpC, encoded by a gene near
The Δ
strain has reduced capsule gene expression but retains the HMV phenotype. We further showed that a regulatory cascade exists in which KvrA and KvrB, the recently characterized MarR-like regulators, and RcsB contribute to capsule regulation through regulation of the
promoter and through additional mechanisms. In a murine pneumonia model, the regulator mutants have a range of colonization defects, suggesting that they regulate virulence factors in addition to capsule. Further testing of the
and
mutants revealed that they have distinct and overlapping functions and provide evidence that HMV is not dependent on overproduction of capsule. This distinction will facilitate a better understanding of HMV and how it contributes to enhanced virulence of hypervirulent strains.
continues to be a substantial public health threat due to its ability to cause health care-associated and community-acquired infections combined with its ability to acquire antibiotic resistance. Novel therapeutics are needed to combat this pathogen, and a greater understanding of its virulence factors is required for the development of new drugs. A key virulence factor for
is the capsule, and community-acquired hypervirulent strains produce a capsule that causes hypermucoidy. We report here a novel capsule regulator, RmpC, and provide evidence that capsule production and the hypermucoviscosity phenotype are distinct processes. Infection studies showing that this and other capsule regulator mutants have a range of phenotypes indicate that additional virulence factors are in their regulons. These results shed new light on the mechanisms controlling capsule production and introduce targets that may prove useful for the development of novel therapeutics for the treatment of this increasingly problematic pathogen.
To date, nutritional epidemiology has relied heavily on relatively weak methods including simple observational designs and substandard measurements. Despite low internal validity and other sources of ...bias, claims of causality are made commonly in this literature. Nutritional epidemiology investigations can be improved through greater scientific rigor and adherence to scientific reporting commensurate with research methods used. Some commentators advocate jettisoning nutritional epidemiology entirely, perhaps believing improvements are impossible. Still others support only normative refinements. But neither abolition nor minor tweaks are appropriate. Nutritional epidemiology, in its present state, offers utility, yet also needs marked, reformational renovation. Changing the status quo will require ongoing, unflinching scrutiny of research questions, practices, and reporting-and a willingness to admit that "good enough" is no longer good enough. As such, a workshop entitled "Toward more rigorous and informative nutritional epidemiology: the rational space between dismissal and defense of the status quo" was held from July 15 to August 14, 2020. This virtual symposium focused on: (1) Stronger Designs, (2) Stronger Measurement, (3) Stronger Analyses, and (4) Stronger Execution and Reporting. Participants from several leading academic institutions explored existing, evolving, and new better practices, tools, and techniques to collaboratively advance specific recommendations for strengthening nutritional epidemiology.
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