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Irrigation methods that can minimize water use are needed, and the performance of recently released ‘KSUZ 0802’ hybrid zoysiagrass (Zoysia matrella × Zoysia japonica) has not been evaluated under such management. Therefore, field experiments were conducted in Manhattan, KS, and Dallas, TX, USA, to compare the amount of water applied and ‘KSUZ 0802’ performance and recovery resulting from irrigation using the following: 1) routine irrigation (1.2 inches/week), 2) evapotranspiration (ET)-based irrigation (60% of reference ET), 3) soil moisture sensor (SMS)-based irrigation, and 4) no irrigation. The experiment was conducted under a rainout shelter in Kansas from 15 Jul to 27 Sep 2019 and 8 Jun to 19 Oct 2020, and in Texas the experiment was conducted under open field conditions from 22 Jun to 9 Sep 2020. The SMS-based irrigation method in Kansas reduced water application by 68% and 52%, respectively, compared with routine or ET-based irrigation. In Texas, the corresponding water savings were 29% and 13%, respectively. The water savings discrepancy was mainly due to differences in local weather conditions and irrigation demand. Visual turf quality of turf receiving SMS-based irrigation remained above the minimally acceptable level throughout the study in Kansas, whereas in Texas, turf quality declined below acceptable level after 2 weeks. In Kansas, turf retained acceptable quality for more than 21 days with no irrigation, and after rewatering, nonirrigated turf recovered back to significant green cover (93% in 2019 and 67% in 2020). ‘KSUZ 0802’ demonstrated good drought tolerance and recovery in Kansas.

Biology laboratory instructors play a key role in creating an optimal environment where college students try hard and enjoy their classroom experiences. This study used achievement goal perspective theory to examine the influence of instructor behaviors on science, technology, engineering, and mathematics (STEM) students' perceptions of the motivational climate (caring, task, ego) and their adaptive (i.e., effort, enjoyment, performance self-esteem, and social self-esteem) and maladaptive (i.e., shame) experiences in the biology laboratory setting. Students (

Summary Fitness trackers (FTs) can help increase activity levels and decrease sedentary behavior. However, researchers have yet to examine whether individuals’ goal orientations influence physical activity behavior in response to FT use. This study examined whether goal orientations predicted participants’ effort and enjoyment while exercising and their reasons for using a FT. Participants (203 females, 57 males; Mage = 42.35 years) reported goal orientations, enjoyment and effort while exercising, and reasons for using an FT. Four stepwise linear regression analyses were calculated to assess the extent that goal orientations predicted effort and enjoyment while exercising and task- and ego-related reasons for using FTs. Both task and ego orientation scores positively predicted effort and enjoyment. Task orientation had a much greater influence than ego orientation over these motivational outcomes. Moreover, task orientation positively predicted task-related reasons for using a FT (e.g., “helps me strive to be my physical best”), while ego orientation positively predicted ego-related reasons for using a FT (e.g., “notifies me that I outperformed others”). Results suggest practitioners and FT manufacturers should consider promoting a task orientation (e.g., define success based on personal effort & improvement) to foster clients’ sustained motivation to engage in PA.

College athletes’ lives have been upended due to the sudden impact of the COVID-19 pandemic. In spring 2020, athletes lost their competition seasons, face-to-face contact with their coaches and tea...

Space radiation in the form of Solar Energetic Protons (SEPs) and Galactic Cosmic Rays (GCR) poses a substantial risk for long-duration space exploration. Active shielding concepts, i.e. shielding a spacecraft with electric and or magnetic fields, has been a topic of interest for more than 50 years. Mass and power requirements have yet to be fulfilled to enable active shielding technology. We present results for a single electric dipole to show the utility of scale-invariance and universal scaling for advancing active shielding concepts. Scattering patterns downstream from the dipole of 2 MeV to 6 MeV electrons and protons show a semi-circular region devoid of incident particles that increases in size with increasing dipole voltage. In particular, results are presented that show how scale-invariant approaches can be leveraged to enable small-scale shields to be built and tested on the ground and then scaled up for in-space use.

An increasingly studied auction format is the asymmetric procurement auction, which features an advantaged bidder selling a good or service to a buyer. Such asymmetric setups, while generally believed to be more realistic, are also more complex. We investigate one such setting where one bidder has a cost advantage. Our central question is whether bidders who are cost-disadvantaged can overcome their inferior cost position. In a design that mirrors real construction procurement auctions, our laboratory experiment tests whether two information asymmetries (more precise cost estimates and knowledge about the cost estimating abilities of a competitor) allow cost-disadvantaged sellers to better compete. We begin by testing bidder performance in a procurement auction where the only asymmetry is due to a cost. In this setting, analytical benchmarks are known. We find – consistent with other studies – that all bidder types submit aggressive bids well below the Nash equilibrium predictions. Over time, subjects submit less aggressive bids, moving closer to what theory would predict. We then extend our experiments to include our novel, multiple asymmetry setup. We find that endowing cost-disadvantaged bidders with higher cost estimate precision benefits the bidder, as one might expect. Notably, providing market knowledge about a rival’s ability to estimate costs may not provide a benefit; in fact, it seems bidders are not able to use this information effectively and performance suffers. Finally, we show how bidders behave myopically when making these decisions. These implications raise important questions about how asymmetries interact in complex auction settings.

The climate in which older adults exercise and participate in sport may play a role in promoting a lifetime commitment to exercising. However, little research has examined the relationship of caring (C) and task-involving (TI) climates, motivation, and well-being with respect to older adult athletes. The purpose of this study was to examine the relationship between Masters swimmers’ perceptions of the climate, effort, enjoyment, and flourishing as well as explore the mediating effects of effort and enjoyment on the relationship between climate and flourishing. U.S. Masters swimmers (n = 294; Mage = 63.57 years; 84.40% White) with 1–80 years of swimming experience (M = 34.54 years) participating in coach-led programs completed an online survey. The results of latent variable, multiple-mediator analyses via structural equation modeling revealed two important contributions to the literature: (1) when Masters swimmers perceived that they were in C and TI climates, they were more likely to report higher levels of effort and greater enjoyment and flourishing; (2) the Masters swimmers’ effort levels directly influenced their flourishing, mediating the relationship between climates and flourishing. This research has important implications for practice and policy, as U.S. Masters Swimming appears to be a fruitful avenue for promoting an enjoyable physical activity that can be experienced throughout a lifetime.

The space radiation environment is dominated by heavy charged particles with atomic numbers ranging from 1 to 93, with broad energy spectra that exceed 10 GeV per nucleon. Despite advances in space radiation modeling and transport, radiation detectors continue to provide critical data for understanding risks of health effects to astronauts in space. In the past, NASA relied on tissue-equivalent proportional counters and passive devices for operational dosimetry; however, in recent years, pixel detectors providing detailed information about the radiation environment through analysis of charged particle tracks have been demonstrated in space. These next-generation detectors, based on Timepix read-out technology, require special analysis considerations that were not necessary or possible for previous dosimetry tools. The impacts of slowing-down and stopped ions on absorbed dose measurements must be explicitly modeled to understand variations with detector orientation. The purpose of the present study is to conclusively demonstrate that while absorbed dose measurements of penetrating charged particles are independent of detector orientation, slowing-down and stopped particles can result in charged particle absorbed dose measurements that are dependent on detector orientation. Monte Carlo simulations of an unshielded detector, irradiated at selected orientations by different kinetic energy domains with fluence spectra representative of two historical solar particle events, are presented to demonstrate the dependence of absorbed dose measurements. Next, results from Monte Carlo simulations of the same energy domains and fluence spectra, isotropically impinging on an anisotropic shield configuration about the detector, are shown, to exhibit the potential for observing varying absorbed doses under realistic environment and shielding conditions. Finally, slowing-down and stopped proton data acquired with Timepix-based detectors at the Tandem Van de Graaff at Brookhaven National Laboratory are used to demonstrate the effect via accelerator-based measurements.

The existence of discriminatory auctions where one class of bidders is offered preferential treatment over another class is controversial. Consider the Affirmative Action policies of the FCC and the Buy-American Act policies of the US Government. The political reasons for such policies are obvious. However, research has shown that there is an economic benefit for such policies in the sense that procurement costs to a buyer may actually decrease as incentives are offered to weaker sellers. In this paper, we test the predictions of Rothkopf et al. (2003) where cost weaker sellers are offered a subsidy in the form of additional payment. For various levels of cost disadvantage, Rothkopf et al (2003), present the optimal subsidy level, bidders’ strategies, bidder profitability, and buyer procurement costs. We test these predictions in a series of controlled experiments. This paper is the first to experimentally test these predictions. Due to the wide use of subsidies not only to support social aims but also their potential to reduce the buyer’s costs, our findings have both financial and societal implications.

This Article explores the limits of judicial settlement of nuclear-weapon disputes through a case study of the Marshall Islands’ cases against India, Pakistan and the UK before the International Court of Justice in 2016. It posits that judicial settlement is limited mainly by the quality of the arguments and evidence submitted by the disputants, not by any limitations inherent in judicial settlement with such politically sensitive disputes. The lawyers in the Marshall Islands’ cases should have taken greater care in crafting their arguments and in tying them explicitly to Article VI of the Nuclear Non-Proliferation Treaty and its customary equivalent.

The purpose of this study was to examine the relationship of students’ perceptions of the motivational climate in their university exercise class to their body esteem (BE) and social physique anxiety (SPA). Students in physical activity classes at a Midwestern university completed a survey measuring their perceptions of the caring, task- and ego-involving features of the exercise class climate, BE (i.e., weight and appearance), and SPA. Canonical correlation analysis revealed one significant function for males and females. Loadings revealed males’ perceptions of a highly caring and task-involving climate with low emphasis on ego-involving climate features were associated with higher weight and appearance BE and lower SPA. Females were similar except the ego-involving climate did not significantly contribute to the model. Continued research may examine the link between motivational climate and BE, but mounting evidence suggests creating positive exercise environments is associated with participants’ adaptive responses, including BE and SPA.

Ethanol occurs naturally in the decaying fruit in which many species of Drosophila (Diptera: Drosophilidae) breed, potentially generating selection for resistance to its toxic and sedating effects. Studies measuring mortality of flies exposed to a range of ethanol concentrations have shown that within Drosophila melanogaster Meigen, populations from temperate regions are more ethanol resistant than ancestral tropical African populations. The high ethanol resistance of temperate D. melanogaster presents a puzzle, however, because breeding and feeding sites in the wild seldom contain enough ethanol to kill even more ethanol-sensitive Afrotropical genotypes. We hypothesize that the ethanol concentrations encountered by temperate populations, though usually sub-lethal, are nonetheless high enough to reduce fitness in other ways, potentially generating indirect selection for genotypes that can survive exposure to unnaturally high ethanol concentrations. As a first step in testing this hypothesis, we compared the effects of a sub-lethal dose of ethanol, comparable to that obtainable from fermenting fruit, on the mating success of males from one European and one Afrotropical population. Ethanol significantly reduced mating success of males from the Afrotropical population, but had no effect on that of males from the European population. We also show that when flies are placed on medium with a realistic concentration of ethanol, considerably more ethanol is absorbed through vapor than through feeding, suggesting that courting males may be unable to avoid being exposed to ethanol. We hypothesize that the higher resistance of temperate populations to being killed by high, unnatural ethanol concentrations may have evolved in part as a correlated response to selection for behavioral insensitivity to natural concentrations.

Passive radiation shielding alone cannot provide adequate protection for astronauts on long-term, deep-space missions. High atomic number and energy (HZE) ions, and/or their secondaries, can penetrate any realistic mass shielding for long-term deep-space missions and cause damage to cells via direct energy deposition and/or through the production of secondary particles and fragmented nuclei. Active shielding, or the use of electromagnetic fields to deflect or stop incoming ions before reaching the spacecraft, has gained substantial attention over the last decade as a way to augment passive shielding. Recently, a mathematical relationship between a dimensionless scaling parameter characterizing the active shield and the incoming ion and a protected area formed on a downstream detector due to the deflection of HZE ions by the applied field was validated in Earth-based laboratory conditions. In the present work, the mathematical formulation is extended to relate electrostatic shielding efficacy with the ability to deflect positively charged ions with parameters relevant to space applications. Additionally, a modified scaling parameter is formulated to characterize the shielding efficacy of a “family” of electrostatic active shielding configurations for reducing flux density for a space-relevant isotropic source of energetic protons. The results of this study demonstrate a strong correlation among dimensionless scaling parameters and shielding efficacy metrics for space radiation-relevant HZE ions in beam and isotropic angular distributions. Furthermore, it establishes a framework for optimizing design of three-dimensional electrostatic shielding configurations to improve space radiation protection for astronauts on exploration-class missions.

Ethanol occurs naturally in the decaying fruit in which many species of Drosophila (Diptera: Drosophilidae) breed, potentially generating selection for resistance to its toxic and sedating effects. Studies measuring mortality of flies exposed to a range of ethanol concentrations have shown that within Drosophila melanogaster Meigen, populations from temperate regions are more ethanol resistant than ancestral tropical African populations. The high ethanol resistance of temperate D. melanogaster presents a puzzle, however, because breeding and feeding sites in the wild seldom contain enough ethanol to kill even more ethanol-sensitive Afrotropical genotypes. We hypothesize that the ethanol concentrations encountered by temperate populations, though usually sub-lethal, are nonetheless high enough to reduce fitness in other ways, potentially generating indirect selection for genotypes that can survive exposure to unnaturally high ethanol concentrations. As a first step in testing this hypothesis, we compared the effects of a sub-lethal dose of ethanol, comparable to that obtainable from fermenting fruit, on the mating success of males from one European and one Afrotropical population. Ethanol significantly reduced mating success of males from the Afrotropical population, but had no effect on that of males from the European population. We also show that when flies are placed on medium with a realistic concentration of ethanol, considerably more ethanol is absorbed through vapor than through feeding, suggesting that courting males may be unable to avoid being exposed to ethanol. We hypothesize that the higher resistance of temperate populations to being killed by high, unnatural ethanol concentrations may have evolved in part as a correlated response to selection for behavioral insensitivity to natural concentrations.

Passive radiation shielding alone is insufficient for protecting astronauts from galactic cosmic ray exposure. Active shields, utilizing electromagnetic fields to deflect heavy charged ions in space, could be used to supplement conventional passive shielding. Due to experimental limitations, simulation capability is crucial for designing effective active shields. The purpose of this work is to validate the Active Shielding Particle Pusher (ASPP) code, used to characterize active shielding efficacy, using beamline measurements conducted at the Brookhaven National Laboratory. Emphasis is placed on (1) comparing shielding efficacy as a function of a scaled dimensionless parameter among various electric dipole sphere sizes and center-to-center distances, (2) comparing shielding efficacy as a function of dipole rotation angle as the voltage applied to each sphere is varied independently, and (3) comparing shielding efficacy observed in measurements and simulations to broaden the validation domain of ASPP. Simulated and measured shielding efficacy data are shown to agree within a factor of 1.10 on average. The results of this work demonstrate that dimensionless scaling of parameters characteristic of the active shield and incident radiation can be used to create scaling laws for a range of ion species relevant for protecting astronauts from galactic cosmic ray exposure at beamline energies.

It is a delicate task to accurately assess the impact of solar particle events (SPEs) on future long-duration human exploration missions. In the past, researchers have used several functional forms to fit satellite data for radiation exposure estimation. In this work we present a segmental power law interpolating algorithm to stream satellite data and get time series of proton spectra, which can be used to derive dosimetric quantities for any short period during which a single SPE or multiple SPEs occur. Directly using the corrected High Energy Proton and Alpha Detector fluxes of GOES, this method interpolates the intensity spectrum of a typical SPE to hundreds of MeV and extrapolates to the GeV level as long as sufficient particles are recorded in the high-energy sensors. The high-energy branch of the May 2012 SPE is consistent with the Band functional fitting, which is calibrated with ground level measurement. Modeling simulations indicate that the input spectrum of an SPE beyond 100 MeV is the major contributor for dose estimation behind the normal shielding thickness of spacecraft. Applying this method to the three SPEs that occurred in 2012 generates results consistent with two sets of in situ measurements, demonstrating that this approach could be a way to perform real-time dose estimation. This work also indicates that the galactic cosmic ray dose rate is important for accurately modeling the temporal profile of radiation exposure during an SPE.

Environmental heterogeneity is thought to be an important process maintaining genetic variation in populations [1-4]: if alternative alleles are favored in different environments, a stable polymorphism can be maintained [1, 5, 6]. This situation has been hypothesized to occur in genes encoding multi-substrate enzymes [7], in which changes that increase activity with one substrate typically decrease activity with others [8-10], but examples of polymorphisms maintained by this mechanism are rare. Here, we present evidence that a polymorphism in an enzyme gene in Drosophila melanogaster is maintained by such a trade-off. The mitochondrially localized aldehyde dehydrogenase in D. melanogaster has two important functions: detoxifying acetaldehyde derived from dietary ethanol [11] and detoxifying larger aldehydes produced as byproducts of oxidative phosphorylation [12]. A derived variant of the enzyme, Leu479Phe, is present in moderate frequencies in most temperate populations but is rare in more ethanol-averse tropical populations. Using purified recombinant protein, we show that the Leu-Phe substitution increases turnover rate of acetaldehyde but decreases turnover rate of larger aldehydes. Furthermore, using transgenic fly lines, we show that the substitution increases lifetime fitness on medium supplemented with an ecologically relevant ethanol concentration but decreases fitness on medium lacking ethanol. The strong, opposing selection pressures, coupled with documented highly variable ethanol concentrations in breeding sites of temperate populations, implicate an essential role for environmental heterogeneity in maintaining the polymorphism.

Crowd ingress and egress occurring before and after large special events results in oversaturation of the traffic network and is a crucial issue event planners and transportation officials must address. Because intersections constitute the greatest restraint in network traffic flows, efficient operation during special event peak flows is crucial. This research focuses on evaluating how well traffic control officers optimize intersection operations during heavily oversaturated conditions associated with large-scale special events. Network traffic data, including volumes, queues, and traffic officer signal/right-of-way phase times, were collected before and after four Clemson University home football games during the 2014 and 2015 season. Actual traffic count volumes were adjusted to account for vehicle queues and used to develop optimal signal timings using Synchro. These results are compared to field-observed intersection operation using officer directed hand-signaling and officer traffic signal pushbutton operation. A microscopic VISSIM model was also created for both manual control and optimized control scenarios to determine average delays for each approach and to improve the interpretation of macroscopic Synchro results. Findings indicate that traffic officers perform well in near saturated conditions; however, optimized signal timings provide reduced approach delay and overall intersection delay in heavily oversaturated conditions. The paper includes recommendations on how traffic officers can improve intersection performance. The paper also describes how results from data collection, analysis, and simulation modeling have been used to make recommendations to law enforcement in evaluating traffic operations and identifying improvements. Intersection control is crucial to the implementation of the overall traffic management plan, and the research findings provide insight to the effectiveness of law enforcement control of intersection operations.

The purpose of this study was to develop an abbreviated version of the Perceived Motivational Climate in Exercise Questionnaire (PMCEQ-A) to provide a more practical instrument for use in applied exercise settings. In the calibration step, two shortened versions’ measurement and latent model values were compared to each other and the original PMCEQ using a three-group CFA invariance testing approach with previously collected exercise setting data (N = 5,427). Based on the model fit and reliability values, the 12-item version performed better than the 17-item version. The resultant 12-item PMCEQ-A’s CFA model estimates were then compared to the PMCEQ’s model values for two different, previously conducted studies of exercise settings (N = 414 and 770). The more parsimonious 12-item PMCEQ-A can be used by exercise psychology researchers to gain insight into members’ perspectives on the motivational climate and may lead to developing effective strategies to enhance members’ experiences and commitment.

BACKGROUND: Demand for respiratory care services and staffing levels of respiratory therapists (RTs) is expected to increase over the next several years. Hence, RT job satisfaction will be a critical factor in determining recruitment and retention of RTs. Determinants of RT job satisfaction measures have received little attention in the literature. This study examines the use of respiratory care protocols and associated levels of RT job satisfaction, turnover intentions, and job stress. METHODS: Four-hundred eighty-one RTs at 44 hospitals responded to an online survey regarding job satisfaction, turnover intentions, and job stress. Random coefficient modeling was used for analysis and to account for the nested structure of the data. RESULTS: Higher levels of RT protocol use were associated with higher levels of job satisfaction, lower rates of turnover intentions, and lower levels of job stress. In addition, RTs with greater experience had higher levels of job satisfaction, and RTs working at teaching hospitals had lower rates of turnover intentions. CONCLUSIONS: The study extends prior research by examining how the use of respiratory care protocols favorably affects RTs9 perceptions of job satisfaction, turnover intention, and job stress. In a time of increasing demand for respiratory care services, protocols may enhance retention of RTs.

The backlash against investor–State arbitration is building, to the point that some commentators even talk about termination or amendment of investment treaties in order to strip international arbitral tribunals of their jurisdiction after the arbitration process already has started. This suggestion has been made in the context of the Philip Morris Asia plain packaging ICSID arbitration involving the Australia–Hong Kong bilateral investment treaty (BIT). This suggestion raises a number of interesting issues for international law and dispute settlement, especially in relation to the limits of the intertemporal rule. States are free to agree to amend or terminate treaties, including ones relating to investment, even before they expire. Such amendments or termination do not have retroactive effects unless the parties to the treaty agree otherwise. This same freedom is available to states in relation to investment treaties. However, the analysis may vary in the context of investor–State arbitration . An arbitration clause in an investment treaty represents an offer made by those states to arbitrate disputes with investors. When investors accept that offer, the consent to arbitrate becomes perfected and cannot be withdrawn unless both parties to the arbitration —the investor and the host state—agree. This conclusion is based on the principle of irrevocability of the consent to arbitrate, which is a pillar of arbitration law and also is established in Article 25 of the ICSID Convention. Moreover, the applicable law to the dispute would be the law that was binding on the parties at the moment of the acts that created the dispute. The same principle applies in state responsibility disputes. Therefore, the argument that Australia simply can amend its BIT with Hong Kong to stop the Philip Morris arbitration might be incorrect. This article explores these issues. (ICSID) Convention on the Settlement of Investment Disputes between States and Nationals of other States (1965), art 25, 71–72 Philip Morris Asia Limited v The Commonwealth of Australia , PCA Case No. 2012–12Vienna Convention on the Law of Treaties (1969), arts 24, 11, 28, 31, 39, 42, 54, 59, 70Australia -Hong Kong Bilateral Investment Treaty (1993) Sanum Investments Limited v Lao People's Democratic Republic , PCA Case No 2013–13 Aguas del Tunari, SA v Republic of Bolivia , ICSID Case No. ARB/02/3, Decision on Respondent's Objections to Jurisdiction, IIC 8 (2005)NAFTA (North American Free Trade Agreement) Free Trade Commission, Notes of Interpretation of Certain Chapter 11 Provisions (2001) Azurix Corp v Argentina , ICSID Case No. ARB/01/12, Decision on Jurisdiction, IIC (2003) Island of Palmas Case (or Miangas) , United States v Netherlands, Award (1949) Pan American Energy LLC v Plurinational State of Bolivia , ICSID Case No ARB/10/8

The Production and Operations Management Society is the largest professional society dedicated to creating and disseminating knowledge in product and process design, operations, and supply chains for the management of manufacturing and services. Its research journal, Production and Operations Management (POM), covers all topics in the discipline and all research paradigms to serve the entire community. Since its inception in 1992, POM has become recognized as a top tier outlet for operations management research. We identify research institutions in the operations management community that have played major roles in developing the journal based on the research of their faculty members and doctoral graduates. Our findings show that the constituency of the journal reflects the constituency of the society.

BACKGROUND: Organizational factors associated with adoption and use of respiratory care protocols have received little attention. This study examines patterns of protocol use and features of a hospital and providers that are associated with respiratory care protocol use. METHODS: Forty-four hospitals and their health-care providers responded to an online survey regarding perceived outcomes of protocol use and their level of support for using protocols. Hospital features (ie, size, teaching status, and use of information systems) were also assessed. Descriptive statistics and multivariate logistic regression were used for analysis. RESULTS: Of the 9 types of respiratory care protocols assessed (ie, asthma, COPD, ARDS, hypoxemia, pneumonia, noninvasive ventilation therapy, supplemental oxygen titration and discontinuation, ventilator weaning, and bronchopulmonary hygiene), the most commonly used were for oxygen titration and ventilator weaning. Large hospitals (> 350 beds) used protocols more widely than smaller hospitals (P = .01). Respondents felt that use of protocols enhanced cost and quality of care. Finally, hospital features that were associated with overall protocol use were stakeholder support for protocol use and use of high-quality hospital information systems. CONCLUSIONS: The study extends prior research by clarifying features of hospitals and providers associated with use of respiratory care protocols. Validation in future hypothesis-testing samples will further advance this knowledge.

A large proportion of duplicates, originating from ubiquitously expressed genes, acquire testis-biased expression. Identifying the underlying cause of this observation requires determining whether the duplicates have altered functions relative to the parental genes. Typically, statistical methods are used to test for positive selection, signature of which in protein sequence of duplicates implies functional divergence. When assumptions are violat ed, however, such tests can lead to false inference of positive selection. More convincing evidence for naturally selected functional changes would be the occurrence of structural changes with similar functional consequences in independent duplicates of the same gene. We investigated two testis-specific duplicates of the broadly expressed enzyme gene Aldehyde dehydrogenase (Aldh )t hat arose in different Drosophila lineages. The duplicates show a typical pattern of accelerated amino acid substitutions relative to their broadly expressed paralogs, with statistical evidence for positive selection in both cases. Importantly, in both duplicates, width of the entrance to the substrate binding site, known a priori to influence substrate specificity, and otherwise conserved throughout the genus Drosophila, has been reduced, resulting in narrowing of the entrance. Protein structure modeling suggests that the reduction of the size of the enzyme’s substrate entry channel, which is likely to shift substrate specificity toward smaller aldehydes, is accounted for by the positively selected parallel substitutions in one duplicate but not the other. Evolution of the testis-specific duplicates was accompanied by reduction in expression of the ancestral Aldh in males, supporting the hypothesis that the duplicates may have helped resolve intralocus sexual conflict over Aldh function.

The lethality of the aggressive brain tumor glioblastoma multiforme (GBM) results in part from its strong propensity to invade surrounding normal brain tissue. Although oncogenic drivers such as epidermal growth factor receptor activation and Phosphatase and Tensin homolog inactivation are thought to promote the motility and invasiveness of GBM cells via phosphatidylinostitol 3-kinase activation, other unexplored mechanisms may also contribute to malignancy. Here we demonstrate that several components of the planar cell polarity (PCP) arm of non-canonical Wnt signaling including VANGL1, VANGL2 and FZD7 are transcriptionally upregulated in glioma and correlate with poorer patient outcome. Knockdown of the core PCP pathway component VANGL1 suppresses the motility of GBM cell lines, pointing to an important mechanistic role for this pathway in glioblastoma malignancy. We further observe that restoration of Nrdp1, a RING finger type E3 ubiquitin ligase whose suppression in GBM also correlates with poor prognosis, reduces GBM cell migration and invasiveness by suppressing PCP signaling. Our observations indicate that Nrdp1 physically interacts with the Vangl1 and Vangl2 proteins to mediate the K63-linked polyubiquitination of the Dishevelled, Egl-10 and Pleckstrin (DEP) domain of the Wnt pathway protein Dishevelled (Dvl). Ubiquitination hinders Dvl binding to phosphatidic acid, an interaction necessary for efficient Dvl recruitment to the plasma membrane upon Wnt stimulation of Fzd receptor and for the propagation of downstream signals. We conclude that the PCP pathway contributes significantly to the motility and hence the invasiveness of GBM cells, and that Nrdp1 acts as a negative regulator of PCP signaling by inhibiting Dvl through a novel polyubiquitination mechanism. We propose that the upregulation of core PCP components, together with the loss of the key negative regulator Nrdp1, act coordinately to promote GBM invasiveness and malignancy.

The decaying fruit in which Drosophila melanogaster feed and breed can contain ethanol in concentrations as high as 6–7%. In this cosmopolitan species, populations from temperate regions are consistently more resistant to ethanol poisoning than populations from the tropics, but little is known about the physiological basis of this difference. I show that when exposed to low levels of ethanol vapor, flies from a tropical African population accumulated 2–3 times more internal ethanol than flies from a European population, giving evidence that faster ethanol catabolism by European flies contributes to the resistance difference. Using lines differing only in the origin of their third chromosome, however, I show that faster ethanol elimination cannot fully explain the resistance difference, because relative to African third chromosomes, European third chromosomes confer substantially higher ethanol resistance, while having little effect on internal ethanol concentrations. European third chromosomes also confer higher resistance to acetic acid, a metabolic product of ethanol, than African third chromosomes, suggesting that the higher ethanol resistance conferred by the former might be due to increased resistance to deleterious effects of ethanol-derived acetic acid. In support of this hypothesis, when ethanol catabolism was blocked with an Alcohol dehydrogenase mutant, there was no difference in ethanol resistance between flies with European and African third chromosomes.

This article represents the first comprehensive analysis of the challenges to the independence and impartiality of international arbitrators in investment disputes. This article evaluates the rules that govern such challenges and asserts that the standards for challenging ICSID arbitrators are not adequate to enable real challenges to arbitrators. Indeed, only one challenge under the ICSID rules has been successful. This in itself is not necessarily problematic assuming the parties agree to dispute settlement with this in mind. This article proposes adjustment of these standards in a variety of ways to help ensure the fairness and perceived fairness of the arbitral process. Finally, this article calls for states and the arbitration community to take steps to combat conflicts of interest of international arbitrators in order to maintain the legitimacy of the regime and to continue to promote growth of the global economy. As the IBA Conflicts of Interest Subcommittee will return to the issue of conflict of interest in international arbitration shortly, this article hopes to influence its efforts, as well as the decisions of states when consenting to arbitration and when considering how to improve the system.

Gene expression responds to the environment and can also evolve rapidly in response to altered selection regimes. Little is known, however, about the extent to which evolutionary adaptation to a particular type of stress involves changes in the within-generation ('plastic') responses of gene expression to the stress. We used microarrays to quantify gene expression plasticity in response to ethanol in laboratory populations of Drosophila melanogaster differing in their history of ethanol exposure. Two populations ('R' populations) were maintained on regular medium, two ('E') were maintained on medium supplemented with ethanol, and two ('M') were maintained in a mixed regime in which half of the population was reared on one medium type, and half on the other, each generation. After more than 300 generations, embryos from each population were collected and exposed to either ethanol or water as a control, and RNA was extracted from the larvae shortly after hatching. Nearly 2000 transcripts showed significant within-generation responses to ethanol exposure. Evolutionary history also affected gene expression: the E and M populations were largely indistinguishable in expression, but differed significantly in expression from the R populations for over 100 transcripts, the majority of which did not show plastic responses. Notably, in no case was the interaction between selection regime and ethanol exposure significant after controlling for multiple comparisons, indicating that adaptation to ethanol in the E and M populations did not involve substantial changes in gene expression plasticity. The results give evidence that expression plasticity evolves considerably more slowly than mean expression.

The performance of the Hakamada Akasofu-Fry, version 2 (HAFv.2) numerical model, which provides predictions of solar shock arrival times at Earth, was subjected to a statistical study to investigate those solar/interplanetary circumstances under which the model performed well/poorly during key phases (rise/maximum/decay) of solar cycle 23. In addition to analyzing elements of the overall data set (584 selected events) associated with particular cycle phases, subsets were formed such that those events making up a particular sub-set showed common characteristics. The statistical significance of the results obtained using the various sets/subsets was generally very low and these results were not significant as compared with the hit by chance rate (50%). This implies a low level of confidence in the predictions of the model with no compelling result encouraging its use. However, the data suggested that the success rates of HAFv.2 were higher when the background solar wind speed at the time of shock initiation was relatively fast. Thus, in scenarios where the background solar wind speed is elevated and the calculated success rate significantly exceeds the rate by chance, the forecasts could provide potential value to the customer. With the composite statistics available for solar cycle 23, the calculated success rate at high solar wind speed, although clearly above 50%, was indicative rather than conclusive. The RMS error estimated for shock arrival times for every cycle phase and for the composite sample was in each case significantly better than would be expected for a random data set. Also, the parameter "Probability of Detection, yes" (PODy) which presents the Proportion of Yes observations that were correctly forecast (i.e. the ratio between the shocks correctly predicted and all the shocks observed), yielded values for the rise/maximum/decay phases of the cycle and using the composite sample of 0.85, 0.64, 0.79 and 0.77, respectively. The statistical results obtained through detailed analysis of the available data provided insights into how changing circumstances on the Sun and in interplanetary space can affect the performance of the model. Since shock arrival predictions are widely utilized in making commercially significant decisions re. protecting space assets, the present detailed archival studies can be useful in future operational decision making during solar cycle 24. It would be of added value in this context to use Briggs-Rupert methodology to estimate the cost to an operator of acting on an incorrect forecast.

El objetivo de este estudio fue analizar la relación entre las percepciones de los empleados sobre el clima motivacional de su Centro de Fitness Corporativo, con su motivación intrínseca hacia la práctica física, así como sus percepciones acerca de la preocupación de los empleadores sobre sus comportamientos saludables. Participaron en el estudio 143 miembros de Centros Corporativos de Fitness del medio sur de los estados Unidos de América, a los que se les administraron los siguientes cuestionarios: 1) el Perceived Motivational Climate in Exercise Questionnaire (con escalas de orientación a metas de ego y tarea); 2) Intrinsic Motivation Inventory (con cuatro subscalas), y 3) la Valued by Employer Scale. Los análisis de regresión revelaron que las percepciones del clima motivacional de ego/tarea estaban positivamente relacionadas con el interés/diversión de los empleados, con su competencia percibida, con el esfuerzo/importancia atribuidas al ejercicio, y con su percepción de ser valorados por sus empleadores. Por lo tanto, el PMCEQ se muestra como una herramienta relevante en los estudios de psicología del ejercicio para medir las percepciones de los empleados acerca del ambiente existente en su Centro de Fitness.

The ErbB3 receptor tyrosine kinase contributes to a variety of developmental processes, and its overexpression and aberrant activation promote tumor progression and therapeutic resistance. Accumulating evidence suggests that tumor overexpression may be mediated by the loss of posttranscriptional negative regulatory mechanisms, such as protein degradation, that normally keep receptor levels in check. Our previous studies indicate that the RING finger E3 ubiquitin ligase Nrdp1, a protein lost in breast and other tumor types, suppresses ErbB3 levels by mediating ligand-independent receptor ubiquitination and degradation. Here we demonstrate that Nrdp1 preferentially associates with the nascent form of ErbB3 to accelerate its degradation, and we show that the two proteins colocalize at the endoplasmic reticulum (ER). Blocking the exit of ErbB3 from the ER does not affect the ability of Nrdp1 to mediate receptor ubiquitination or degradation, while functional disruption of the conserved ER-associated degradation (ERAD) pathway ATPase VCP/p97 leads to the Nrdp1-dependent accumulation of ubiquitinated ErbB3 but blocks receptor degradation. Further evidence indicates that the ErbB3 targeted by Nrdp1 for degradation is properly folded and fully functional. Collectively, these observations point to a novel mechanism of receptor tyrosine kinase quantity control wherein steady-state levels of signaling-competent receptor are dictated by an ER-localized degradation pathway.

Little is known about the roles of aldehyde dehydrogenases in non-vertebrate animals. We recently showed that in Drosophila melanogaster, an enzyme with ~70% amino acid identity to mammalian ALDH2 is necessary for detoxification of dietary ethanol. To investigate other functions of this enzyme, DmALDH, encoded by the gene Aldh, we compared two strains homozygous for Aldh-null mutations to two closely related wild type strains in measures of fitness and stress resistance in the absence of ethanol. Aldh-null strains have lower total reproductive rate, pre-adult viability, resistance to starvation, and possibly longevity than wild-type strains. When maintained under hyperoxia, Aldh nulls die more quickly and accumulate higher levels of protein carbonyls than wild-types, thereby providing evidence that DmALDH is important for detoxifying reactive aldehydes generated by lipid peroxidation. However no effect of Aldh was seen on protein carbonyl levels in flies maintained under normoxia. It is possible that Aldh nulls experience elevated rates of protein carbonylation under normoxia, but this is compensated (at a fitness cost) by increased rates of degradation of the defective proteins. Alternatively, the fitness defects of Aldh nulls under normoxia may result from the absence of one or more other functions of DmALDH, unrelated to protection against protein carbonylation.

Aggressive behavior among females is observed in many species, but the mechanisms of this behavior have historically been understudied. In many species of rodents, winter-like short day photoperiods induce increased aggression levels compared to summer-like long day photoperiods. Recent reports in hamsters show that short days also increase aggression in females. We examined the effects of photoperiod on aggression in female California mice, and for the first time compare brain activity of aggression-tested female rodents under different photoperiods. We observed that female California mice were more aggressive when housed in short days versus long days. Intriguingly, we also observed that under long days female attack latency decreases with repeated testing in resident intruder tests. These data suggest that winner effects that have been described in males may also occur in females. We also used the expression of phosphorylated extracellular signal-regulated kinases (pERK) in the brain to estimate brain activity during aggression tests. pERK can alter neuronal activity in the short term and in the long term can act as a transcription factor. Using immunoblot analyses we observed that aggression-induced pERK expression in the female bed nucleus of the stria terminalis (BNST) and medial amygdala occurs under both long and short days. Thus, the mechanisms controlling increased aggression under short days are still unclear and additional study is needed.

Preclinical data suggested that bryostatin-1 (bryo) could potentiate the cytotoxicity of cisplatin when given prior to this drug. We designed a phase I study to achieve tolerable doses and schedules of bryo and cisplatin in combination and in this sequence.Patients with non-hematologic malignancies received bryo followed by cisplatin in several schedules. Bryo was given as an 1 and a 24 h continuous infusion, while cisplatin was always given over 1 h at 50 and 75 mg/m(2); the combined regimen was repeated on an every 3-week and later on an every 2-week schedule. Bryo doses were escalated until recommended phase II doses were defined for each schedule. Patients were evaluated with computerized tomography every 2 cycles.Fifty-three patients were entered. In an every 2-week schedule, the 1-h infusion of bryo became limited by myalgia that was clearly cumulative. With cisplatin 50 mg/m(2) its recommended phase II dose was 30 microg/m(2). In the 3-week schedule, dose-limiting toxicities were mostly related to cisplatin effects while myalgias were tolerable. Pharmacokinetics unfortunately proved to be unreliable due to bryo's erratic extraction. Consistent inhibition of PKC isoform eta (eta) in peripheral blood mononuclear cells was observed following bryo.Bryo can be safely administered with cisplatin with minimal toxicity; however, only four patients achieved an objective response. Modulation of cisplatin cytotoxicity by bryo awaits further insight into the molecular pathways involved.