Background: To explore the prediction value of PI-RADS v2 in high-grade prostate cancer and establish a prediction model combined with related variables of prostate cancer. Material and Methods: A total of 316 patients with newly discovered prostate cancer at Zhongnan Hospital of Wuhan University and Renmin Hospital of Wuhan University from December 2017 to August 2019 were enrolled in this study. The clinic information as age, tPSA, fPSA, prostate volume, Gleason score and PI-RADS v2 score have been collected. Univariate analysis was performed based on every variable to investigate the risk factors of high-grade prostate cancer. ROC curves were generated for the risk factors to distinguish the cut-off points. Logistic regression analyses were used to investigate the independent risk factors of high-grade prostate cancer. Nomogram prediction model was generated based on multivariate logistic regression analysis. The calibration curve, ROC curve, leave-one-out cross validation and independent external validation were performed to evaluate the discriminative ability, accuracy and stability of the nomogram prediction model. Results: Of 316 patients, a total of 187 patients were diagnosed as high-grade prostate cancer. Univariate analysis showed tPSA, fPSA, prostate volume, PSAD and PI-RADS v2 score were significantly different between the high- and low-grade prostate cancer patients. Univariate and multivariate logistic regression analyses showed only tPSA, prostate volume and PI-RADS v2 score were the independent risk factors of high-grade prostate cancer. The nomogram could predict the probability of high-grade prostate cancer, with a sensitivity of 79.4% and a specificity of 77.6%. The calibration curve displayed good agreement of the predicted probability with the actual observed probability. AUC of the ROC curve was 0.840 (0.797-0.884). Leave-one-out cross validation indicated the nomogram prediction model could classify 81.4% cases accurately. External data validation was performed with a sensitivity of 80.6% and a specificity of 77.3%, the Kappa value was 0.5755. Conclusions: PI-RADS v2 score had the value in predicting high-grade prostate cancer and the nomogram prediction model may help early diagnose the high risk prostate cancer.


This paper presents a tool and a novel Fast Invariant Transform (FIT) algorithm for language independent e-documents access. The tool enables a person to access an e-document through an informal camera capture of a document hardcopy. It can save people from remembering/exploring numerous directories and file names, or even going through many pages/paragraphs in one document. It can also facilitate people's manipulation of a document or people's interactions through documents. Additionally, the algorithm is useful for binding multimedia data to language independent paper documents. Our document recognition algorithm is inspired by the widely known SIFT descriptor [4] but can be computed much more efficiently for both descriptor construction and search. It also uses much less storage space than the SIFT approach. By testing our algorithm with randomly scaled and rotated document pages, we can achieve a 99.73% page recognition rate on the 2188-page ICME06 proceedings and 99.9% page recognition rate on a 504-page Japanese math book [2].


Carers of individuals with eating disorders (EDs) report high levels of burden and distress and describe a number of unmet needs. As a result, a number of interventions have been designed to support carers, including the "Maudsley eating disorder collaborative care skills workshops," which comprise six 2-hr workshops delivered over 3 months for parents and carers of people with EDs. The current study aimed to test a proof-of-concept that this workshop could be effectively delivered in 1 day. An additional aim was to assess whether the workshop had direct effects on carer skills. A nonexperimental repeated measures research design was employed, giving measures before and after a 1-day workshop. Results suggested significant increases in carer self-efficacy and carer skills, with moderate to large effect sizes. Qualitative analyses supported these results whilst also generating ideas to improve the 1-day workshop.


The double-dividend hypothesis' suggests that increased taxes on polluting activities can provide two kinds of benefits. The first is an improvement in the environment, and the second is an improvement in economic efficiency from the use of environmental tax revenues to reduce other taxes such as income taxes that distort labor supply and saving decisions. In this paper, we make four main points. First, the validity of the double-dividend hypothesis cannot logically be settled as a general matter. Second, the focus on revenue in this literature is misplaced. We demonstrate that three policies have equivalent impacts on the environment and on labor supply. One of those policies raises revenue from the environmental component of the reform, another loses revenue, and a third has no revenue associated with it. Third, what matters is the creation of privately-held scarcity rents. Policies that raise product prices through some restriction on behavior may create scarcity rents. Unless those rents are captured by the government, such policies are less efficient at ameliorating an environmental problem than are policies that do not create rents. Finally, we distinguish between two types of command and control regulations on the basis of whether they create scarcity rents.


Hybrid films prepared from 3-glycidoxypropyltrimethoxysilane have been widely used as organic–inorganic materials for several applications. Tailoring the coating surface should disclose new possibilities of applications in biomaterials as functional interfaces for cells and enzymes. In this work we have designed the synthesis of 3-glycidoxypropyltrimethoxysilane hybrid films to modify the surface properties without additional surface functionalization steps. The pH of the precursor sols has been changed from highly basic to acidic and neutral pH and then the sols have been used to deposit highly transparent films. The analysis by infrared spectroscopy has shown that the synthetic conditions allow tuning the degree of condensation of the silica network and the percentage of epoxide ring opening. A precise control of these two parameters enables the formation of a smart surface library where hydroxyl or epoxide groups or the mixed presence of both change the hydrophobicity of the surface and thus its capability of binding molecules and nano-objects.


Ten subjects participated in an experiment in which each was presented with series of paired stimuli separated by 1000 msec. The first stimulus was a click. The second stimulus was either of two visual patterns, concentric circles or a star figure. Figure selection on each trial was determined by a random procedure.

There were four experimental conditions: 1) Subjects pressed a switch following the presentation of either figure. 2) Subjects pressed a switch following the presentation of the star only. 3) Subjects guessed prior to the clicks, which figure would appear as S2; no overt motor response was required. 4) Subjects had to add 7 to a cumulative sum following a star, and subtract 7 following the circles; no overt motor response was required.

Using data obtained from a vertex to linked ear derivation we conclude that the CNV is not contingent on a motor response to S2.

The electrical potentials recorded following S2, and in particular the positive-going "resolution" of the CNV seemed to vary systematically with the experimental conditions. An application of Tucker's three-mode factor analysis to this CNV is reported.


To improve student performance, standards have been introduced in educational policy in the Netherlands and abroad. Performance standards are related to effective educational practices like holding high expectations and using formative assessment, both of which are aspects of diagnostic teaching. An educational policy measure like performance standards will only have an effect when teachers are willing and able to implement it. This study explores primary school teachers' attitudes, concerns and knowledge of performance standards and diagnostic teaching through in-depth interviews (N=9) and a questionnaire survey (N=793). Teachers appear to be relatively unfamiliar with performance standards. Nevertheless, they expect standards will positively influence their daily practice and student performance. They do express concerns about the potential effect of performance standards on weaker students. Teachers fear that the basic level will be too difficult for weaker students and the lowest performance standard will therefore be impossible to reach. Currently, teachers often do not discuss with their colleagues which performance levels they expect from different groups of students. Performance standards may stimulate these discussions on learning goals.


The problem of implicit semantics was approached in this paper with a broad understanding of presuppositions, implications, entailments, etc., as derivable information created by three different kinds of contexts in the four stages of meaning generation. Liens are viewed as meanings implied by the speaker and/or inferred by the hearer in a real act of communication. As meaning generation is assumed to be an activity, liens are consequently treated as dynamic processes involving psychological associations, rational deductions, and imagination. Each stage of semiogenesis provides a potential possibility for a variety of liens. Most of them are dismissed and cancelled at the subsequent stages of meaning generation so that the final perceptive product-an understood utterance-appears to have only several liens which remain
relevant for a given set of linguistic, referential and situational
contexts and for the majority of the speakers.


ABSTRACT The objective of this study was to evaluate the effects of seven nitrogen (N2)-fixing and/or phosphorus (P)-solubilizing and siderophore-producing microorganism based bio-fertilizers in single and triple strain combinations isolated from the acidic rhizospheric soil of native tea, grapevine, and wild red raspberries. As a result of this study, bacterial efficiency was found to be variable and depended on the bacterial strains and evaluated growth parameters. Plant growth-promoting rhizobacteria (PGPR) has improved macro- and micro-nutrient concentrations in grapevine leaves, and stimulated plant growth. Triple inoculation and single inoculation based bio fertilizers were found to stimulate overall plant growth, including shoot and leaf weight, main shoot length, leaf ground index, chlorophyll, nitrogen, zinc and iron content of grapevine cv 'Italy'. Bio-fertilizers increased the nutrients such as nitrogen, zinc and iron concentrations and consequently increased the chlorophyll content of the leaves.


Multi-city time series studies of particulate matter (PM) and mortality and morbidity have provided evidence that daily variation in air pollution levels is associated with daily variation in mortality counts. These findings served as key epidemiological evidence for the recent review of the United States National Ambient Air Quality Standards (NAAQS) for PM. As a result, methodological issues concerning time series analysis of the relation between air pollution and health have attracted the attention of the scientific community. Critics have raised concerns about the adequacy of current model formulations. Time series data on pollution and mortality are generally analyzed using log-linear, Poisson regression models for overdispersed counts with the daily number of deaths as outcome, the (possibly lagged) daily level of pollution as a linear predictor, and smooth functions of weather variables and calendar time used to adjust for time-varying confounders. Investigators around the world have used different approaches to adjust for confounding, making it difficult to compare results across studies. To date, the statistical properties of these different approaches have not been comprehensively compared. To address these issues, we quantify and characterize model uncertainty and model choice in adjusting for seasonal and long-term trends in time series models of air pollution and mortality. First,we conduct a simulation study to compare and describe the properties of statistical methods commonly used for confounding adjustment. We generate data under several confounding scenarios and systematically compare the performance of the different methods with respect to the mean squared error of the estimated air pollution coefficient. Second, we apply and compare the modelling approaches to the National Morbidity, Mortality, and Air Pollution Study (NMMAPS) database which is comprised of daily time series of several pollutants, weather variables, and mortality counts covering the period 1987--2000 for the largest 100 cities in the United States. We find that the NMMAPS estimates for the national average effect of PM(10) at lag 1 on mortality are robust to the different strategies for adjusting for seasonal and long-term trends.


There has never been a more challenging time to practice land use planning and zoning law in New York. With goals of sustainability at the forefront of the land use regulatory agenda, this brief account of recent developments in land use law highlights some discernable trends, namely: the modernization and increased flexibility of New York State planning and zoning enabling acts, the inspired local initiatives and lethargic State response to affordable housing issues, and the increasing impact of alternative energy systems on local regulatory schemes. Part I of this article explores the impacts on community development caused by the many modifications to New York State's planning and zoning enabling acts over the last two decades. Particularly, the article identifies the delegation of extensive discretionary authority to local governments as New York's signature approach to land use control. Part II discusses "affordable housing" as a key attractant for judicial action and local government response. With the exception of the Long Island Workforce Housing Act in 2008, the State has been slow to act on judicial calls to action, forcing local governments to develop unique solutions in order to provide affordable housing. Finally, Part III notes the challenges being faced by lawyers and planners in light of growing preference for alternative energy systems, with specific focus on reactions to Wind Energy and Solar Energy installations.


[1] Statistical modeling techniques and the Vaganov-Shashkin (VS) forward model of tree ring formation were used to investigate tree growth response of Pinus tabulaeformis to climate variations in semi-arid north central China. Both statistical and process-based modeling techniques were shown to be capable of simulating and evaluating climate-tree growth relationships for the study area, but the process-based VS model produced results that were more physically interpretable. Statistical modeling results indicate that both moisture and temperature have significant effects on tree growth during the growing season, with the most important months being May–August. The VS modeled results validated the above statistical modeling results, and further clarified the effects on tree growth of the seasonal distribution of temperature and soil moisture, soil moisture status prior to the growing season, and the start and end dates of the growing season. Under current and projected climate scenarios, our modeling results suggest significant tree growth reduction in north central China, and the possibility that regional forests may reduce their capacity to sequester carbon.


Recombination dynamics in a variety of InGaN/GaN quantum systems has been studied by time resolved photoluminescence (PL). We have discovered that the time-decay of PL exhibits a scaling law: the nonexponential shape of this decay is preserved for quantum wells and quantum boxes of various sizes while their decay time varies over several orders of magnitude. To explain these results, we propose an original model for electron-hole pair recombination in these systems, combining the effects of internal electric fields and of carrier localization on a nanometer-scale. These two intricate effects imply a separate localization of electrons and holes. Such a microscopic description accounts very well for both the decays shape and the scaling law.


We use a novel approach to address the question of whether a union of sovereign countries can efficiently raise and allocate a budget, even when members are purely self-interested and participation is voluntary. The main innovation of our model is to explore the link between budget contributions and allocation that arises when countries bargain over union outcomes. This link stems from the distribution of bargaining power being endogenously determined. Generically, it follows that unstructured bargaining gives an inefficient result. We find, however, that efficiency is achieved with fully homogenous countries, and when countries have similar incomes and the union budget is small. Moreover, some redistribution arises endogenously, even though nations are purely self-interested and not forced to participate in the union. A larger union budget, however, entails a tradeoff between equality and efficiency. We also analyze alternative institutions and find that majority rule can improve efficiency if nations who prefer projects with high public good spillovers are endogenously selected to the majority coalition. Exogenous tax rules, such as the linear tax rule in the EU, which is designed to increase efficiency on the contribution margin, can also improve overall efficiency despite decreasing the efficiency of the allocation of funds.


The extant literature on comparative Corporate Social Responsibility (CSR) often assumes functioning and enabling institutional arrangements, such as strong government, market, and civil society, as a necessary condition for responsible business practices. Setting aside this dominant assumption, and drawing insights from a case study of Fidelity Bank, Nigeria, we explore why and how firms still pursue and enact responsible business practices in what could be described as challenging and non-enabling institutional contexts for CSR. Our findings suggest that responsible business practices in such contexts are often anchored on some CSR adaptive mechanisms. These mechanisms uniquely complement themselves and inform CSR strategies. The CSR adaptive mechanisms and strategies, in combination and in complementarity, then act as an institutional buffer (i.e. 'institutional immunity'), which enables firms to successfully engage in responsible practices irrespective of their weak institutional settings. We leverage this understanding to contribute to CSR in developing economies, often characterised by challenging and non-enabling institutional contexts. The research, policy and practice implications are also discussed. Paper Type: Research paper


Background. The symptom profiles of young adolescent rugby and non-contact sports were investigated over one sport season. Objectives. To compare the concussion symptom profiles of rugby players with those of non-contact sport players over a sport season. Methods. In a non-equivalent quasi-experimental design, a group of rugby players ( n =99) were compared with a demographically equivalent group of non-contact sport participants ( n =74). The computerised Immediate Post-concussion Assessment and Cognitive Testing (IMPACT) symptom scale was employed to evaluate and compare pre-season and post-season assessment of both groups. Results. Independent comparative analyses revealed that the damaging effects owing to exposure to concussive and sub-concussive incidents appear to be more pronounced in the rugby group in terms of symptomatic presentation compared with the controls. Conclusion. The damaging effects are compounded during a rugby season as a result of sub-concussive and concussive events.


Objectives Uterine carcinosarcoma is a rare, aggressive form of uterine cancer with a high recurrence rate and poor survival at all stages. We sought to evaluate the outcomes of patients treated with chemotherapy versus a combination of chemotherapy and radiation (chemoradiation) to determine survival. Methods A multicenter retrospective analysis of patients with stage I–IV carcinosarcoma was conducted from January 2000 to December 2017. Inclusion criteria were primary surgical management, defined as hysterectomy ± salpingo-oophorectomy, comprehensive surgical staging and/or tumor debulking, followed by adjuvant chemotherapy or chemoradiation. Differences in the frequencies of stage, cytoreduction status, treatment delays and sites of disease recurrence were identified using Pearson's χ2 test. Progression-free and overall survival rates were calculated using Kaplan-Meier estimates. Results Final analysis included 148 patients; 40.5% (n=60) chemotherapy and 59.5% (n=88) chemoradiation. The mean age was 67 years (range 39–89). Stage distribution included 24.3% stage I, 12.2% stage II, 37.2% stage III, and 26.3% stage IV. There was no difference in the frequency of stage (p=0.81), cytoreduction status (p=0.61), treatment delays (p=0.57), or location of recurrence (p=0.97) between cohorts. The most frequent location of recurrence was the abdomen (50.0%). The median progression-free survival favored chemoradiation over chemotherapy (15 vs 11 months, respectively), as did the median overall survival (26 vs 20 months, respectively). Chemoradiation was associated with a statistically significant improvement in 2 year progression-free survival (22.5% vs 13.6%; p=0.006) and 2 year overall survival (50.0% vs 35.6%; p=0.018) compared with chemotherapy alone. On subanalysis of patients receiving chemoradiation, 'sandwich sequencing' (chemotherapy–radiation–chemotherapy) was associated with superior overall survival compared with alternate therapy sequences (chemotherapy–radiation and radiation–chemotherapy) (34 months vs 14 months and 14 months, respectively) (p=0.038). Conclusions Chemoradiation was associated with improvement in both progression-free and overall survival for all stages of carcinosarcoma compared with chemotherapy alone.


Abstract. Atmospheric measurements of the ozone-depleting substance CFC-113a (CCl3CF3) are reported from ground-based stations in Australia, Taiwan, Malaysia and the United Kingdom, together with aircraft-based data for the upper troposphere and lower stratosphere. Building on previous work, we find that, since the gas first appeared in the atmosphere in the 1960s, global CFC-113a mixing ratios have been increasing monotonically to the present day. Mixing ratios of CFC-113a have increased by 40 % from 0.50 to 0.70 ppt in the Southern Hemisphere between the end of the previously published record in December 2012 and February 2017. We derive updated global emissions of 1.7 Gg yr−1 on average between 2012 and 2016 using a two-dimensional model. We compare the long-term trends and emissions of CFC-113a to those of its structural isomer, CFC-113 (CClF2CCl2F), which still has much higher mixing ratios than CFC-113a, despite its mixing ratios and emissions decreasing since the 1990s. The continued presence of northern hemispheric emissions of CFC-113a is confirmed by our measurements of a persistent interhemispheric gradient in its mixing ratios, with higher mixing ratios in the Northern Hemisphere. The sources of CFC-113a are still unclear, but we present evidence that indicates large emissions in East Asia, most likely due to its use as a chemical involved in the production of hydrofluorocarbons. Our aircraft data confirm the interhemispheric gradient as well as showing mixing ratios consistent with ground-based observations and the relatively long atmospheric lifetime of CFC-113a. CFC-113a is the only known CFC for which abundances are still increasing substantially in the atmosphere.


[1] We present Cassini Visual and Infrared Mapping Spectrometer observations of infrared auroral emissions from the noon sector of Saturn's ionosphere revealing multiple intense auroral arcs separated by dark regions poleward of the main oval. The arcs are interpreted as the ionospheric signatures of bursts of reconnection occurring at the dayside magnetopause. The auroral arcs were associated with upward field-aligned currents, the magnetic signatures of which were detected by Cassini at high planetary latitudes. Magnetic field and particle observations in the adjacent downward current regions showed upward bursts of 100–360 keV light ions in addition to energetic (hundreds of keV) electrons, which may have been scattered from upward accelerated beams carrying the downward currents. Broadband, upward propagating whistler waves were detected simultaneously with the ion beams. The acceleration of the light ions from low altitudes is attributed to wave-particle interactions in the downward current regions. Energetic (600 keV) oxygen ions were also detected, suggesting the presence of ambient oxygen at altitudes within the acceleration region. These simultaneous in situ and remote observations reveal the highly energetic magnetospheric dynamics driving some of Saturn's unusual auroral features. This is the first in situ identification of transient reconnection events at regions magnetically conjugate to Saturn's magnetopause.


This paper will complete and conclude the Forlixt presentation, linking with that of Cristina Valentini in this volume. In a bank of multimodal and multilingual data about film dialogues the methodology for extracting and analyzing data differs fundamentally from the approaches which have to date been applied to corpora of written texts. In addition to the methods and examples used for a macrostructural analysis which Valentini's paper has already stressed, we show all the aspects of research that are possible on a microstructural level through a complex system of tagging which can be combined with a free text search. In particular, the potential for microstructural analysis is fully apparent when linguistic information is linked with iconic, aural and situational details accessible from video clips. We will thus present an analysis (contrasting Italian with German) which relates to a discourse element closely connected with the pragmatic aspect of communication in diverse situations. The different stages of analysis have the aim not only of broadening knowledge about one specific case, but chiefly to illustrate one of a number of possible ways in which dialogue can be studied. As well as indicating differences and similarities between the linguistic and pragmatic structure of the two languages, the system allows for a focus on all the problems that characterize the strategies for translations and adaptations. Finally, we will also give examples of how to seek out clues, on a diachronic level, about the appearance and disappearance of linguistic phenomena, which may at the same time refer back to semiotic codes according to the relative social and ethnocultural context .


Phenological variation in Thompson Seedless grapevines grafted on different rootstocks and own rooted vines was assessed for two consecutive years and the reasons for such variations were studied through biochemical analysis. Uniform and early bud sprouting was recorded in the vines grafted on 110R rootstock and on own roots, which was attributed to increased peroxidase activity and protein content in the buds before bud burst. Increased fruitfulness on 110R rootstock and own rooted vines was attributed to the increased phosphorus and protein content of those vines and reduced vegetative vigour measured in terms of shoot length, cane diameter and pruned biomass. Thompson Seedless grafted on Dogridge rootstock recorded the highest nitrogen content, increased shoot length, cane diameter and increased pruned biomass attributing to reduced fruitfulness. The highest concentration of phenolic compounds and amino acids was recorded in the fruits produced on 110R rootstock, while it was least on St. George and own roots. Significant variation in the accumulation pattern of amino acids (especially proline and arginine) was observed, with the least proline/arginine ratio recorded on 110R rootstocks at the time of harvest, indicating the variation in the days taken for fruit ripening on different rootstocks.


Identifying the intrinsic electrocatalytic activity of nanomaterials is challenging, as their characterization usually requires additives and binders whose contributions are difficult to dissect. Herein, we use nano impact electrochemistry as an additive-free method to overcome this problem. Due to the efficient mass transport at individual catalyst nanoparticles, high current densities can be realized. High-resolution bright-field transmission electron microscopy and selected area diffraction studies of the catalyst particles before and after the experiments provide valuable insights in the transformation of the nanomaterials during harsh oxygen evolution reaction (OER) conditions. We demonstrate this for 4 nm sized CoFe2O4 spinel nanoparticles. It is revealed that these particles retain their size and crystal structure even after OER at current densities as high as several kA·m-2. The steady-state current scales with the particle size distribution and is limited by the diffusion of produced oxygen away from the particle. This versatilely applicable method provides new insights into intrinsic nanocatalyst activities, which is key to the efficient development of improved and precious metal-free catalysts for renewable energy technologies.


Significance Donald Trump and a small group of emerging leaders around the world have been labeled as outliers in the ways that they think and communicate with others. Are they really anomalies, or do they fit into larger political trends? This study adds to existing scholarship by analyzing two important psychological dimensions, analytic thinking and confidence, in 12 large corpora of political texts representing political leaders of various levels in both the United States and other countries as well as 4 corpora of cultural texts. Rather than being anomalous, linguistic analyses find that, over the last century, there have been consistent declines in analytic thinking and rises in confidence in the ways that political leaders communicate with the public. From many perspectives, the election of Donald Trump was seen as a departure from long-standing political norms. An analysis of Trump's word use in the presidential debates and speeches indicated that he was exceptionally informal but at the same time, spoke with a sense of certainty. Indeed, he is lower in analytic thinking and higher in confidence than almost any previous American president. Closer analyses of linguistic trends of presidential language indicate that Trump's language is consistent with long-term linear trends, demonstrating that he is not as much an outlier as he initially seems. Across multiple corpora from the American presidents, non-US leaders, and legislative bodies spanning decades, there has been a general decline in analytic thinking and a rise in confidence in most political contexts, with the largest and most consistent changes found in the American presidency. The results suggest that certain aspects of the language style of Donald Trump and other recent leaders reflect long-evolving political trends. Implications of the changing nature of popular elections and the role of media are discussed.


Bacterial infection often involves toxin-mediated damage to the host. This can occur at mucosal epithelial surfaces, in subepithelial tissues (involving connective tissue, blood vessels and host defence cells), or at organ or tissue sites distant from the focus of infection. This paper deals with host damage at each of these levels and examples have been selected of toxins that have a well defined role in pathogenesis and for which evidence is less clear cut. Current views of mechanisms of host damage are presented along with summaries of mode of action at the molecular level where this is known. Certain unifying features of mechanisms of toxin action on host cells are emphasised. Modern genetic methods and gene cloning techniques should help in the assessment of the role of individual toxic factors where pathogenesis is multifactorial, and preliminary examples of this approach are mentioned. The search for new toxins continues and this is illustrated with reference to the toxins involved in the staphylococcal scalded skin syndrome and staphylococcal toxic shock syndrome. This overview is intended to convey an impression of the rapid development that has taken place in knowledge of the role of toxins in pathogenesis.


Abstract. Variations in surface and near-surface ground temperatures (GST) dominate the evolution of the ground thermal regime over time and represent the upper boundary condition for the subsurface. Focusing on the Lapires talus slope in the south-western part of the Swiss Alps, which partly contains massive ground ice, and using a joint observational and modelling approach, this study compares and combines observed and simulated GST in the proximity of a borehole. The aim was to determine the applicability of the physically based subsurface model COUP to accurately reproduce spatially heterogeneous GST data and to enhance its reliability for long-term simulations. The reconstruction of GST variations revealed very promising results, even though two-dimensional processes like the convection within the coarse-blocky sediments close to the surface or ascending air circulation throughout the landform ("chimney effect") are not included in the model. For most simulations, the model bias revealed a distinct seasonal pattern mainly related to the simulation of the snow cover. The study shows that, by means of a detailed comparison of GST simulations with ground truth data, the calibration of the upper boundary conditions – which are crucial for modelling the subsurface – could be enhanced.


As it is known from the current research and studies that travel time of vehicles is the most reliable parameters to measure the cost of a link. Cost modeling of routes has many useful applications in dynamic route selection strategies e.g. route selection for emergency vehicles. Travel time of an individual vehicle passing a road segment is a function of many parameters which includes of road geometry, traffic flow characteristics, driver»s behaviors and region-specific rules and regulations, length of the segment, number of lanes, lane width, traffic flow, traffic volume and density, average speed of vehicles, vehicles composition and the ratio of turn movements on ramps. Moreover, the average travel time of vehicles on freeways is also dependent on some parameters that vary from country to country e.g. traffic regulations, driving rules, driver»s behavior and the construction of roads. Current mathematical models and simulation software»s lack the implementation of all these parameters and hence the results of these models are mostly different from the actual. The calibration of simulation software is always required to reduce this difference. The estimation of travel time using some numerical computation or simulation software»s is not reliable. This paper describes the modeling of travel time as a cost/metric of segments on a freeway. In it, regression models are used to evaluation the travel time for a throughway segment using traffic statistics acquired from field surveys. The validity of the models is explained with their statistical significance. Regression models are equally beneficial for any region if the data sets are quite large and enough parameters are included in the model. In regression analysis, the relationships among different variables are estimated. In it, different modeling techniques are used to find the relationship between dependent and independent variables. More precisely, the analysis helps to realize how the dependent variable changes with the variation of any of the independent variables keeping other variables fixed. In this work, statistical techniques i.e. regression modeling and analysis of variance (ANOVA) has been used to evaluate the impact of each independent variable (parameters) on the travel time. Finally, a multivariate regression model is used to approximate the time of travel. The estimated time is related to the actual travel time from the real field data and the model fitness is evaluated. Our dataset constitutes of four independent parameters and one dependent parameters. Independent variable (Inputs): 1 Length of the segment 2 No of lanes in the segment 3 Flow of traffic on the segment 4 Average Speed of vehicles on the segment Dependent variable (Response) 1 Travel Time Regression analysis has been used as a statistical technique to find the response variable (travel time). In this paper it is proposed to find the travel time for a particular connection using regression models applied to actual traffic data sets collected from field surveys. Real traffic data for several segments from different freeways has acquired and analyzed them using regression models. The probable travel time was compared with actual travel time for each segment of the highway and it was found that the estimation using regression models reveals the significant level of accuracy. R-Studio is being used in the statistical analysis of the data. We computed the regression equation for the estimation of travel time for all the given four parameters (distance, lanes, flow, speed) using coefficients, β0, β1, β2, β3 and β4. Figure1 shows the actual travel time of the vehicle and the estimated travel time which is obtained by the regression analysis.


User privacy is widely affected by the occurrence of privacy-invasive software (PIS) on the Internet. Various forms of countermeasures try to mitigate the negative effects caused by PIS. We use a computer forensic tool to evaluate an anti-spyware tool, with respect to found PIS over a four years period. Within the anti-spyware tool PIS was slowly identified, caused classification problems, and formely classified PIS were sometimes excluded. Background information on both PIS and countermeasure techniques are also presented, followed by discussions on legal disputes between developers of PIS and vendors of countermeasures.


We investigate in how far interpolation mechanisms based on the nearest-neighbor rule (NNR) can support cancer research. The main objective is to usethe NNR to predict the likelihood of tumorigenesis based on given risk factors.By using a genetic algorithm to optimize the parameters of the nearest-neighbourprediction, the performance of this interpolation method can be improved sub-stantially. Furthermore, it is possible to detect risk factors which are hardly ornot relevant to tumorigenesis. Our preliminary studies demonstrate that NNR-based interpolation is a simple tool that nevertheless has enough potential to beseriously considered for cancer research or related research.


The negotiations of the international Anti-Counterfeiting Trade Agreement and Trans Pacific Partnership Agreement have been conducted largely in secret, elevating intellectual property piracy to the level of national security concerns for purposes of accessing information through the Freedom of Information Act (FOIA). However, the level of actual secrecy has been tiered, with corporate interests enjoying far more access to negotiation information than the general public. At the same time, similar intellectual property issues were negotiated in the relative transparency of Congress' debate over the Stop Online Piracy Act and PROTECT IP Act, allowing for much greater public involvement. With national security concerns as the backdrop, the focus of this Article is the use of national security arguments to prevent the public, and more specifically, public experts (i.e., the "nerds") from accessing information through FOIA about the creation of international intellectual property law. The Article proposes ways to address the information failures existing in international intellectual property lawmaking and international lawmaking more generally from policy and, as introduced in this Article, theoretical perspectives.


Objective To investigate the role of a rapid sideline Head Injury Assessment Form (HIAF) in the clinical diagnosis of concussion in elite Australian football. Design Validation study Setting/participants The study was conducted in all 207 matches of the professional competition during the 2015 season. Interventions The HIAF comprised 12 individual tests based on previously validated clinical features1 and video signs2 of concussion. Experienced team physicians were required to complete the HIAF for any incident potentially resulting in a concussion. The HIAF directs team physicians to either permanently remove the player (9 of 12 tests), or conduct a more detailed assessment (e.g. SCAT3, 3 of 12 tests). Where possible, the tests were conducted by both direct assessment and video review of the incident. At the end of the season, data on all clinically confirmed concussions was collected from team physicians. Main results 135 HIAFs were submitted throughout the 2015 season resulting in 44 players permanently removed from play for concussion. 8 confirmed concussions were not identified during the match. When compared to information on clinically confirmed concussions, the HIAF captured concussive incidents with 89% sensitivity (95% CI: 75.44% – 96.21%) and 98% specificity (95% CI: 92.03% – 99.72%). Conclusions The HIAF was demonstrated to have a high level of sensitivity and specificity. It is a useful precursor to the SCAT3 for the sideline diagnosis of concussion, in most cases providing a faster and more prescriptive assessment. A modified version of the HIAF may be useful in lower levels of competition.


Introduction A water budget is an accounting of water movement into and out of, and storage change within, some control volume. Universal and adaptable are adjectives that reflect key features of water-budget methods for estimating recharge. The universal concept of mass conservation of water implies that water-budget methods are applicable over any space and time scales (Healy et al ., 2007). The water budget of a soil column in a laboratory can be studied at scales of millimeters and seconds. A water-budget equation is also an integral component of atmospheric general circulation models used to predict global climates over periods of decades or more. Water-budget equations can be easily customized by adding or removing terms to accurately portray the peculiarities of any hydrologic system. The equations are generally not bound by assumptions on mechanisms by which water moves into, through, and out of the control volume of interest. So water-budget methods can be used to estimate both diffuse and focused recharge, and recharge estimates are unaffected by phenomena such as preferential flow paths within the unsaturated zone. Water-budget methods represent the largest class of techniques for estimating recharge. Most hydrologic models are derived from a water-budget equation and can therefore be classified as water-budget models. It is not feasible to address all water-budget methods in a single chapter. This chapter is limited to discussion of the "residual" water-budget approach, whereby all variables in a water-budget equation, except for recharge, are independently measured or estimated and recharge is set equal to the residual. This chapter is closely linked with Chapter 3, on modeling methods, because the equations presented here form the basis of many models and because models are often used to estimate individual components in water-budget studies. Water budgets for streams and other surface-water bodies are addressed in Chapter 4. The use of soil-water budgets and lysimeters for determining potential recharge and evapotranspiration from changes in water storage is discussed in Chapter 5. Aquifer water-budget methods based on the measurement of groundwater levels are described in Chapter 6.


The separators of Li–S batteries are modified with polypyrrole (PPy) nanotubes, PPy nanowires and reduced graphene oxide (rGO), respectively. All the conductive materials for the separator surface decoration can inhibit the migration of lithium polysulfides in the electrolyte and decrease the polarization of the sulfur cathode. Thus, the shuttle effect and redistribution of the active material can be suppressed during the charge/discharge process, resulting in enhanced performance. Moreover, the adsorption effect of PPy to lithium polysulfides is stronger compared to that of rGO, and the wettability of the PPy modified separators towards the electrolyte is much better, resulting in further enhanced electrochemical performance of Li–S batteries. Particularly, with approximately 2.5–3 mg cm−2 sulfur loading, the Li–S battery using the PPy nanotube modified separator displays an initial discharge capacity of 1110.4 mA h g−1, and a retained capacity of 801.6 mA h g−1 after 300 cycles at 0.5C, demonstrating an average coulombic efficiency up to 90.6% in the LiNO3-free electrolyte.


The climate literacy movement aspires to help members of the general public understand the global climate system, locate and assess scientifically credible climatic information, communicate about climate change in an educated and objective manner, and make informed and responsible decisions in response to climate-change impacts. When these goals are not met, society will likely be further imperiled by the effects of a changing climate. Climate literacy programs have traditionally promoted education on the biophysical science of the climate system but have largely failed to integrate relevant knowledge from the social sciences. We argue that understanding human behavior and the social drivers of climate change are essential for the public to fully appreciate the climate system, and that this knowledge can inform decision making related to climate-change mitigation and adaptation. Teaching students to evaluate different forms of evidence will also improve climate literacy and lead them to ask how scientists know what they know. Finally, we suggest two new social science principles that could advance interdisciplinary climate literacy goals.


These evidence-based guidelines are an updated version of those published in 2006. They have been produced after a literature review of the treatment and prophylaxis of methicillin-resistant Staphylococcus aureus (MRSA). The guidelines aim to complement those recently published for the antibiotic treatment of common and emerging community-onset MRSA infections in the UK. The guidelines have reviewed and updated, where appropriate, previous recommendations, taking into account any changes in the UK epidemiology of MRSA, ongoing national surveillance data and the value of new antistaphylococcal agents licensed for use in UK practice. Emerging therapies that have not been licensed for UK use are not reviewed, but their future potential role has been mentioned where deemed appropriate. Recommendations are given for the treatment of common infections caused by MRSA, elimination of MRSA from carriage sites and prophylaxis of surgical site infection.


This essay argues that principles should play a limited role in policy-making. It first illustrates the dilemma of timely action in the face of uncertain unintended consequences. It then introduces the precautionary and proactionary principles as different alignments of knowledge and action within the policy-making process. The essay next considers a cynical and a hopeful reading of the role of these principles in public policy debates. We argue that the two principles, despite initial appearances, are not all that different when it comes to formulating public policy. We also suggest that allowing principles to determine our actions undermines the sense of autonomy necessary for true action.


The application of titania materials to gas sensing devices based on thin films are of limited utility because they only operate at a high working temperature and exhibit in general a low sensitivity. To overcome these constraints, a new type of oxygen sensor based on mesoporous titania thin films working at room temperature under UV irradiation has been developed. The increased density of charge carriers induced by the photoconductive effect, has been used to enhance the sensitivity of the thin oxide layers. Mesostructured titania films have been prepared via self-assembly and thermal processing to remove the organic template obtaining anatase nanocrystals. The mesoporous films show a striking decrease of the current in the presence of oxygen that acts as an electron scavenger. Mesoporous samples exhibit a much higher response with respect to dense titania, due to the higher surface area and the larger number of surface defects.


This article describes the development and score validation of a 36-item measure of six academic orientations in college students: structure dependence, creative expression, reading for pleasure, academic efficacy, academic apathy, and mistrust of instructors. Results from three studies indicate that the measuring instrument, the Survey of Academic Orientations (SAO), has six factorially distinct scales (Study 1) whose scores are stable across different semesters, yielding test-retest coefficients that range from .63 to .86 (Study 2). Also, each of the six scales relates in expected ways to basic personality traits, yielding validity coefficients of .30 to .69 (Study 3). Scores on the six scales are internally consistent, yielding coefficients alpha that range from .59 to .85 (Studies 1-3). Scale scores and a summative score of all 36 items, called the Adaptiveness index, are examined for their potential in predicting a variety of important student outcomes.


Studies were performed on canine cardiac Purkinje fibers to evaluate the effects of manganese on membrane electrogenesis. The results indicate that manganese has a calciumlike effect on the excitatory sodium current and inhibitory effects on potassium conductance and slow inward current. The calciumlike effect of manganese on sodium current was reflected through a leftward (toward less negative potentials) and downward shift in the curve relating maximum upstroke velocity to membrane potential. The inhibitory action of manganese on potassium conductance was suggested by the following observations. (1) Manganese caused an initial increase in action potential duration largely due to a lengthening of the plateau and decreases in the rates of phase 3 and terminal repolarization. (2) Manganese increased the rate of diastolic depolarization. (3) Manganese blocked the initial fall in maximum diastolic potential accompanying rapid stimulation. (4) Manganese in high concentrations caused generalized depolarization which was reversed by rapid stimulation and by increased extracellular potassium concentrations. The action of manganese to block slow inward current was indicated by the eventual shortening of the plateau and by the elimination of responses initiated from low levels of membrane potential (< −55 mv). In addition to these effects, manganese also reduced membrane excitability, eliminated arrhythmic beats occurring during low-frequency electrical stimulation, and caused membrane hyperpolarization which was blocked by tetrodotoxin.


More than 150 municipal utilities (so-called Stadtwerke) were established in Germany from the beginning of the millennium, bringing the total number of Stadtwerke currently established within the country to approximately 900. With responsibility for more than half of the supply of electricity, gas and heat in Germany, these Stadtwerke play a central role in the transformation of the energy sector, or Energiewende. In addition, due to their local and regional ties, Stadtwerke have a particular role to play in energy politics, the economy and across society. This article focuses on the motives behind, and grounds for, the current wave of newly established Stadtwerke. Further, it discusses the factors that were critical to the successful formation of new Stadtwerke in recent years. The results of our survey indicate that the establishment of municipal Stadtwerke is a suitable measure to implement the energy transition at the local level, whereby the concept of public value has a high level of importance for the local decision-makers. Collaboration and cooperation, as well as a resilience-oriented strategy, are important success factors for new Stadtwerke.


In this paper we discuss and review several aspects of the effect of boundary conditions and structured environments on dispersion and resonance interactions involving atoms or molecules, as well as on vacuum field fluctuations. We first consider the case of a perfect mirror, which is free to move around an equilibrium position and whose mechanical degrees of freedom are treated quantum mechanically. We investigate how the quantum fluctuations of the mirror's position affect vacuum field fluctuations for both a one-dimensional scalar and electromagnetic field, showing that the effect is particularly significant in the proximity of the moving mirror. This result can be also relevant for possible gravitational effects, since the field energy density couples to gravity. We stress that this interaction-induced modification of the vacuum field fluctuations can be probed through the Casimir-Polder interaction with a polarizable body, thus allowing to detect the effect of the mirror's quantum position fluctuations. We then consider the effect of an environment such as an isotropic photonic crystal or a metallic waveguide, on the resonance interaction between two entangled identical atoms, one excited and the other in the ground state. We discuss the strong dependence of the resonance interaction with the relative position of the atomic transition frequency with the gap of the photonic crystal in the former case, and with the cut-off frequency of waveguide in the latter.


The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer is triggered by receptor binding to mediate the entry of the virus into cells. Most structural studies of Env trimers have utilized truncated soluble gp140 Envs stabilized with the I559P and SOS changes. Here we present evidence indicating that these stabilizing changes have a profound impact on the conformation of Env, moving Env away from the native pretriggered Env conformation. Our studies underscore the need to acquire structural information on the pretriggered Env conformation, which is recognized by most broadly reactive neutralizing antibodies. ABSTRACT The entry of human immunodeficiency virus into host cells is mediated by the envelope glycoprotein (Env) trimeric spike, which consists of three exterior gp120 subunits and three transmembrane gp41 subunits. The trimeric Env undergoes extensive conformational rearrangement upon interaction with the CD4 receptor, transitioning from the unliganded, "closed" State 1 to more-open downstream State 2 and State 3 conformations. Changes in "restraining" amino acid residues, such as leucine 193 and isoleucine 423, destabilize State 1 Env, which then assumes entry-competent, downstream conformations. The introduction of an artificial disulfide bond linking the gp120 and gp41 subunits (SOS) in combination with the I559P (IP) change has allowed structural characterization of soluble gp140 (sgp140) trimers. The conformation of these SOSIP-stabilized sgp140 trimers has been suggested to represent the closed native State 1 conformation. Here we compare the impact on the membrane Env conformation of the SOSIP changes with that of the well-characterized changes (L193R and I423A) that shift Env to downstream States 2 and 3. The results presented here suggest that the SOSIP changes stabilize Env in a conformation that differs from State 1 but also from the downstream Env conformations stabilized by L193R or I423A. IMPORTANCE The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer is triggered by receptor binding to mediate the entry of the virus into cells. Most structural studies of Env trimers have utilized truncated soluble gp140 Envs stabilized with the I559P and SOS changes. Here we present evidence indicating that these stabilizing changes have a profound impact on the conformation of Env, moving Env away from the native pretriggered Env conformation. Our studies underscore the need to acquire structural information on the pretriggered Env conformation, which is recognized by most broadly reactive neutralizing antibodies.


People will start seeking tax-exempt debt forgiveness under the Public Service Loan Forgiveness ("PSLF") program in October of 2017 after satisfying the requirements of 10 years of post-October 1, 2007 employment in a "public service job." I estimate that eventually 200,000 people a year or more will obtain debt forgiveness under this program, at a total cost to the Treasury of $12 billion/year or more. Estimates are that up to one-quarter of all employment will qualify as a public service job.
For such a large and costly program the precise eligibility criteria are crucial. The statutory definition of a public service job is very broad and specifically lists numerous categories of public service, and is in some ways ambiguous. The Department of Education ("DOE") in 2008 issued regulations regarding PSLF program employment eligibility, but those regulations have serious deficiencies. First of all, the regulations improperly define a public service job in a manner that is inconsistent with the statute by imposing a "public service organization" employer requirement that is not in the statute. This requirement works to disqualify some statutorily-listed public service employment from debt forgiveness eligibility, in particular public services employment provided on behalf of for-profit businesses or certain non-profit employers, and also improperly allows eligibility for debt forgiveness for some employees of private non-profit employers who are not employed to provide a qualifying public service. Second, the regulations fail to clarify vague statutory language regarding what constitutes "public" service, most importantly regarding the scope of "public interest law services." The DOE has also recently rescinded several previously granted certifications of employment as qualifying on the basis of a newly imposed restrictive "primary purpose of the employer" requirement that is not in the governing statute nor in the DOE regulations, actions that have been challenged in court by the American Bar Association. Even if this restriction is upheld, which appears unlikely, there is a strong argument that the DOE should be estopped from rescinding prior certifications. In order to avoid unnecessary litigation once the expected large number of applications for debt forgiveness begin to be filed after October of 2017, I recommend that the DOE first seek Congressional action to clarify the contours of the PSLF program's employment eligibility statute, and while awaiting such action it should rescind its public service organization eligibility requirement that is inconsistent with the statute, clarify that there is no primary purpose of the employer requirement, and provide much more detailed guidance regarding the contours of the various statutorily-specified forms of qualifying public service, especially public interest law service. If PSLF program eligibility is to be either narrowed or expanded this should be done through appropriate legislation, and not through unauthorized and somewhat covert DOE actions.


Gαs protein–coupled receptors reduce the sensitivity of cells to the morphogen Sonic Hedgehog. GPCRs reduce sensitivity to Sonic Hedgehog In the developing spinal cord, Sonic Hedgehog (SHH) released from the notochord and floor plate induces overlying neural progenitor cells (NPCs) to differentiate into different neural cell types in a concentration-dependent manner. Pusapati et al. found that loss of the G protein–coupled receptor (GPCR) GPR161 sensitized both cultured fibroblasts and NPCs to SHH. The ability of Gαs, which is activated by GPR161, to negatively regulate SHH signaling did not strictly depend on GPR161, suggesting that other GPCRs that couple to Gαs may also attenuate SHH signaling. Although GPCR kinase 2 (GRK2) is proposed to promote SHH signaling by removing GPR161 from the primary cilium, the authors found that GRK2 enhanced SHH signaling independently of GPR161. GRK2, GPR161, and Gαs tuned cellular sensitivity to SHH likely by affecting the extent of protein kinase A activity, a negative regulator of SHH signaling (see also Focus by Sharpe and de Sauvage). The morphogen Sonic Hedgehog (SHH) patterns tissues during development by directing cell fates in a concentration-dependent manner. The SHH signal is transmitted across the membrane of target cells by the heptahelical transmembrane protein Smoothened (SMO), which activates the GLI family of transcription factors through a mechanism that is undefined in vertebrates. Using CRISPR-edited null alleles and small-molecule inhibitors, we systematically analyzed the epistatic interactions between SMO and three proteins implicated in SMO signaling: the heterotrimeric G protein subunit GαS, the G protein–coupled receptor kinase 2 (GRK2), and the GαS-coupled receptor GPR161. Our experiments uncovered a signaling mechanism that modifies the sensitivity of target cells to SHH and consequently changes the shape of the SHH dose-response curve. In both fibroblasts and spinal neural progenitors, the loss of GPR161, previously implicated as an inhibitor of basal SHH signaling, increased the sensitivity of target cells across the entire spectrum of SHH concentrations. Even in cells lacking GPR161, GRK2 was required for SHH signaling, and Gαs, which promotes the activation of protein Kinase A (PKA), antagonized SHH signaling. We propose that the sensitivity of target cells to Hedgehog morphogens, and the consequent effects on gene expression and differentiation outcomes, can be controlled by signals from G protein–coupled receptors that converge on Gαs and PKA.


The dominant role played by the state in the financing, regulation, and provision of primary and secondary education reflects the widely-held belief that education is necessary for personal and societal well-being. The economic organization of education depends on political as well as market mechanisms to resolve issues that arise because of contrasting views on such matters as income inequality, social mobility, and diversity. This book provides the theoretical framework necessary for understanding the political economy of education -- the complex relationship of education, economic growth, and income distribution -- and for formulating effective policies to improve the financing and provision of education. The relatively simple models developed illustrate the use of analytical tools for understanding central policy issues. After offering a historical overview of the development of public education and a review of current econometric evidence on education, growth, and income distribution, the authors lay the theoretical groundwork for the main body of analysis. First they develop a basic static model of how political decisions determine education spending; then they extend this model dynamically. Applying this framework to a comparison of education financing under different regimes, the authors explore fiscal decentralization; individual choice between public and private schooling, including the use of education vouchers to combine public financing of education with private provision; and the social dimension of education -- its role in state-building, the traditional "melting pot" that promotes cohesion in a culturally diverse society.


We abstract optical waveguide meshes into graph representations to solve practical light distribution problems, leveraging structures and algorithms from graph theory. One of the substantial problems is single input-output signal routing inside the meshes. Whilst respecting physical restrictions regarding the directional flow of light, three types of graph representations are compared in terms of feasibility for solving this problem. Of the three types, the directed graph with eight artificial nodes proves to be superior. A representation of this kind takes us one step closer to a fully programmable optical core with complex functionalities, especially in photonic meshes with feedback paths.


We present new, full-orbit observations of the infrared phase variations of the canonical hot Jupiter HD 189733b obtained in the 3.6 and 4.5 μm bands using the Spitzer Space Telescope. When combined with previous phase curve observations at 8.0 and 24 μm, these data allow us to characterize the exoplanet's emission spectrum as a function of planetary longitude and to search for local variations in its vertical thermal profile and atmospheric composition. We utilize an improved method for removing the effects of intrapixel sensitivity variations and robustly extracting phase curve signals from these data, and we calculate our best-fit parameters and uncertainties using a wavelet-based Markov Chain Monte Carlo analysis that accounts for the presence of time-correlated noise in our data. We measure a phase curve amplitude of 0.1242% ± 0.0061% in the 3.6 μm band and 0.0982% ± 0.0089% in the 4.5 μm band, corresponding to brightness temperature contrasts of 503 ± 21 K and 264 ± 24 K, respectively. We find that the times of minimum and maximum flux occur several hours earlier than predicted for an atmosphere in radiative equilibrium, consistent with the eastward advection of gas by an equatorial super-rotating jet. The locations of the flux minima in our new data differ from our previous observations at 8 μm, and we present new evidence indicating that the flux minimum observed in the 8 μm is likely caused by an overshooting effect in the 8 μm array. We obtain improved estimates for HD 189733b's dayside planet–star flux ratio of 0.1466% ± 0.0040% in the 3.6 μm band and 0.1787% ± 0.0038% in the 4.5 μm band, corresponding to brightness temperatures of 1328 ± 11 K and 1192 ± 9 K, respectively; these are the most accurate secondary eclipse depths obtained to date for an extrasolar planet. We compare our new dayside and nightside spectra for HD 189733b to the predictions of one-dimensional radiative transfer models from Burrows et al. and conclude that fits to this planet's dayside spectrum provide a reasonably accurate estimate of the amount of energy transported to the night side. Our 3.6 and 4.5 μm phase curves are generally in good agreement with the predictions of general circulation models for this planet from Showman et al., although we require either excess drag or slower rotation rates in order to match the locations of the measured maxima and minima in the 4.5, 8.0, and 24 μm bands. We find that HD 189733b's 4.5 μm nightside flux is 3.3σ smaller than predicted by these models, which assume that the chemistry is in local thermal equilibrium. We conclude that this discrepancy is best explained by vertical mixing, which should lead to an excess of CO and correspondingly enhanced 4.5 μm absorption in this region. This result is consistent with our constraints on the planet's transmission spectrum, which also suggest excess absorption in the 4.5 μm band at the day–night terminator.


1. Introduction One of the more important aspects of the work of the Road Research Laboratory is to develop better materials for surfacing roads. By 'better materials' is meant materials having greater resistance to cracking and deformation, greater durability against the effects of weather and greater ability to maintain an even and non-skid surface for traffic. The surfacing materials in common use are concrete, asphalt and bituminous macadams; these consist of a mixture of mineral aggregates bound together with either Portland cement, bitumen or tar. The Laboratory is therefore concerned with obtaining an understanding of the properties of crushed rock and gravel aggregates that influence the behaviour of these surfacing materials. This paper describes briefly the research into one important requirement of aggregates used in bituminous road surfacings. This requirement is that the exposed aggregate should not become polished by the action of traffic, since the degree of slipperiness of many types of bituminous surfacing is directly related to the extent to which the aggregate becomes polished. 2. Laboratory test The first step was to develop a laboratory apparatus to determine how the polishing occurred. The aim was to reproduce as closely as possible the conditions of wear to which stone is subjected in the road surface. Thus, the apparatus (Pl. 1a) comprises a pneumatic-tyred wheel which rotates in contact with another wheel on the flat periphery of which are mounted small specimens of ⅜-in sized chipping bedded in a cement mortar (Pl. 1b). The wheel carrying the specimens is


In this study, vacuum filtration, coagulation-flocculation, electrocoagulation and centrifugation were applied to separate emulsified oils from water. Two different types of cutting oils (BOR and EAL) were used in the preparation of oil emulsions. BOR has smaller oil droplets than EAL when they are mixed by water. It was not possible to separate BOR from water by microfiltration but 81.7% removal efficiency was obtained for EAL. Alum and ferric chloride were used as coagulants and optimum coagulant dosages, mixing time and pH were determined by performing jar tests. When alum was used as the coagulant, the removal efficiencies for BOR and EAL were 90% and 98%, respectively. In the case of ferric chloride, 98% oil removal was obtained for both emulsions. However, the optimum ferric chloride dosages were much higher than alum. The optimum alum and ferric chloride dosages for BOR emulsion were 0.83 g/L and 6 mg/L, respectively. In the case of EAL emulsion, the corresponding amounts were 4 mg/L and 8 mg/L. The flocculation time was determined around 45 minutes. In order to obtain 98% BOR removal, the emulsion was centrifuged at an angular velocity of 3000 rpm after the coagulation-flocculation process. On the other hand, when BOR and EAL were separated by electrocoagulation, 95% removal rates can be obtained for both oils applying 40 V difference to the aluminum electrodes for 35 minutes. According to the removal efficiencies obtained from the experiments and the preliminary cost analysis it can be concluded that the best method for separating emulsified oils from waters is the electrocoagulation.


A key actor is missing in transitional justice discourse. While ex-combatant and DDR issues have generated rich literatures, transitionary armed movements groups as such are neglected. This article addresses part of this research gap, focusing on the agency of armed movements with respect to three key TJ themes: transition, law, and truth processes in the law-based 'rechtsstaat'. Drawing on examples from South Africa, Namibia, Israel/Palestine and the Basque country, a framework for analyzing this agency is mapped by exploring the political opportunity structures presented by truth processes, and the processes' implications for the movements' mobilising structures and framing processes. This analytical framework is grounded using original Northern Ireland data drawn from interviews with former IRA activists, IRA public statements, and Sinn Fein election manifestos. The data suggests that transitionary armed opposition movements see transitional justice as a site for continuing their political projects. This presents political opportunities to inflict damage on their opponents, but also, given the victim-perpetrator character of these movements, it is potentially a site of attrition. The truths emerging from transitional processes may reflect the degrees of agency, entrepreneurship (including deliberate silences), and resource deployed in the process, by state and non-state actors.


I. INTRODUCTION II. GENETICS 101: BASIC EDUCATIONAL FOUNDATION A. Dissecting the Double Helix of Deoxyribonucleic Acid B. The Human Genome Project C. The HabMap Project D. The Future of Genetic Research III. THE HISTORY OF THE U. S. PATENT SYSTEM AND THE EFFECT OF THE LEAHY-SMITH AMERICA INVENTS ACT A. Legislative History of the United States Patent System B. The Common Law Approach to Gene Patents 1. The Impact of Diamond v. Chakrabarty 2. The Ongoing Debate of the Ass'n for Molecular Pathology v. U.S. Patent & Trademark Office 3. Society's Split on Gene Patents i. Monopolies ii. The Effects on Science and Genetic Research iii. Patenting an Aspect of Nature IV. LEAHY-SMITH AMERICA INVENTS ACT ("AIA") A. Patent Processing 1. First-Inventor-to-File i. Changes Made by the FITF System ii. Exceptions to the FITF System 2. Submissions by Third Parties 3. Inventors Oath 4. Tax Strategies with Patent Applications 5. Human Organisms 6. Prioritized Examination 7. Faster Patent Processing 8. Derivation Proceedings B. Post-Patent Proceedings and Review 1. Inter Partes Review 2. Post Grant Review 3. Supplemental Examination C. Litigation 1. Defenses to Infringement Cases 2. Joinder of Parties in Infringement Litigation Cases 3. Venue 4. Advice of Counsel Defense 5. False Marketing Cases D. The AIA's Answers for Gene Patents and Scientific Research V. THE IMPACTS OF GENE PATENTS ON SCIENTIFIC RESEARCH AND THE NEED FOR LEGISLATIVE GUIDELINES A. The Creation of a New Patent Category: Gene Patents B. A Reduction in Patent Protection to Implement Collaboration C. GenBank Database D. Patent Pooling VI. CONCLUSION I. INTRODUCTION Kathy Hopkins was the eldest of seven children. She was a single mother, and the sole supporter of her son. In the spring of 2007, Kathy was diagnosed with stage four glioblastoma multiform ("GBM"). GBM is a compilation of small tumors within the glia or the precursors of the glia within the central nervous system. (1) This form of brain cancer is "the most aggressive of the glimoas." (2) Most individuals with GBM die in less than a year from the date of diagnosis. (3) Even with treatment, the life expectancy of individuals diagnosed with GBM only increases from two months to a year. (4) Kathy's tumor was inoperable. Her only options for treatment included chemotherapy and radiation. Determined that the medical community would discover a cure, Kathy chose to try every medical procedure available in hopes that she could defeat GBM. on April 1, 2009, two years after her diagnosis, at the age of 63, Kathy passed away surrounded by her loving family. (5) Greg Knittel was the Classics' Chairman, Dean of Teachers, and founding soccer coach at St. Ignatius High School in Cleveland, Ohio. (6) Greg, fondly known by his students and the Ignatius community as "Doc," was forced to retire from St. Ignatius when he lost the ability to control his car on his drive into work. (7) Greg was suffering from amyotrophic lateral sclerosis ("ALS"). (8) The major cause(s) of ALS, also commonly referred to as Lou Gehrig's (9) disease, are unknown. (10) Ten percent of all ALS cases are genetically based. (11) ALS causes neurons (12) to slowly waste away and eventually die, resulting in "muscle weakening, twitching, and eventually the inability to move the arms, legs, and body." (13) This is caused by the inability of neurons to "send messages to [the] muscles" of the body after neurons have died. (14) Individuals with ALS typically die within three to five years after being diagnosed. (15) only about twenty five percent of individuals diagnosed with ALS live beyond five years. (16) On February 5, 2013 Greg "Doc" Knittel passed away surrounded by his loving family. (17) Kathy and Greg are only two individuals, out of millions, who have suffered or who are currently suffering from incurable diseases. …


Trauma, including major Orthopaedic Surgery, results in an immuno-inflammatory response which is variable in systemic effects.This response is patient specific. The systemic effects may be exaggerated and cause distal organ damage. This study assesses the effects of elective hip and knee arthroplasty on liver function tests. A prospective study of liver function in 316 patients (168 males and 148 females) undergoing elective total hip and knee joint replacement was undertaken by one surgeon using standardised anaesthetic, surgical and post-operative protocols. Alanine aminotransferase (ALT), Aspartate transaminase (AST), Alkaline phosphatase (ALP) and Gammaglutamyl transpeptidase (GGT) were assessed pre-operatively and at one day, one week and six weeks following surgery. There were 166 hip and 150 knee replacement patients. Of the hip replacements, 35% were cemented, 35% hybrid and 30% cementless. All knee replacements were cemented: ALT levels (IU) pre-operatively were 20, one day 17, one week 45.5 and at six weeks 17. AST levels (IU) pre-operatively were 21, one day 22, one week 38 and at six weeks 19. ALP levels (IU) pre-operatively were 77, one day 57, one week 88.5 and at six weeks 90. GGT levels (IU) pre-operatively were 24, one day18, one week 68 and at six weeks 29. For all enzymes there was a highly significant (p ALP, also a bone enzyme, remained elevated at six weeks. There was no significant difference for age or gender. There was no significant difference for cemented, hybrid or cementless hips. Liver function tests become elevated one week following elective joint replacement. This is not related to cement. The cause is probably multifactorial and major likely contributory factors are patients9 immuno-inflammatory response and drug effects. Surgeons should be aware of this phenomenon and undertake pre-operative LFT screening routinely.


Based on the conclusion that attainment of a phala entails a specific, fetterbreaking-experience, in Chapter 4 we proceed to establish that a supramundane "phala" in the Suttas is a fetter-breaking-experience together with its ongoing effects, as opposed to the Pāli commentarial usage in which a "phala" of the Path is just a "peak-experience" that lasts only a few moments following the fetterbreaking "path" moment. This chapter includes: 1) Definition of the word "phala": This extracts the various meanings attributed to the word "phala" in general. 2) References in the Nikāyas to Path, fetter-breaking-experience and the effect (of the fetter-breaking-experience) as three different phenomena: This extracts evidence from the Nikāyas to highlight references to fetter-breaking-experiences and their effects as distinctly different phenomena. 3) Implications of the thesis of "Path, fetter-breaking-experience and effect".


The non-Abelian Berry phase is an essential feature of non-Abelian anyons for
the realization of topological quantum computation. This thesis is primarily a study
about the numerical calculation of the Berry phase of non-Abelian anyons in the
Kitaev honeycomb lattice model. It is also a guide for experimental the realizations
of the actual brading process.
We give an introduction to the theory of non-Abelian anyons, briefly discussing in
what kind of systems they are realized, and their possible use in topological quantum
computation. Non-Abelian anyons are studied within the Kitaev honeycomb model
where they are realized on the plaquettes of the honeycomb lattice. The Kitaev honeycomb
model can be solved exactly by using various fermionization methods. In
this thesis, we review a solution based on Jordan-Wigner types of fermions which
transform Hamiltonian to a fermionic quadratic form. This kind of fermionization
procedure is quite general and can be applied to any trivalent spin lattice models.
Moreover, we introduce Hartree-Fock-Bogoliubov method to solve general quadratic
fermionic Hamiltonian and employ Bloch-Messiah theorem in order to write ground
state wave function explicitly. Later, we apply these methods to honeycomb model
and study the eigenstates of the model so that we can do the Berry phase calculation.
The final chapter explains the details of the numerical calculation of the non-Abelian
Berry phase. First, we show how to create and adiabatically move vortices in the honeycomb
model. A brief review of the Berry phase is given including some discussion
about a numerical approach. Later on Thouless' representation of the ground state is
introduced to calculate the Berry phase. All these theoretical tools are applied to a
4 vortex configuration of the model to calculate the non-Abelian Berry phase of the
system on a particular path in the parameter space.


Tuning complex machine learning systems is challenging. Machine learning typically requires to set hyperparameters, be it regularization, architecture, or optimization parameters, whose tuning is critical to achieve good predictive performance. To democratize access to machine learning systems, it is essential to automate the tuning. This paper presents Amazon SageMaker Automatic Model Tuning (AMT), a fully managed system for gradient-free optimization at scale. AMT finds the best version of a trained machine learning model by repeatedly evaluating it with different hyperparameter configurations. It leverages either random search or Bayesian optimization to choose the hyperparameter values resulting in the best model, as measured by the metric chosen by the user. AMT can be used with built-in algorithms, custom algorithms, and Amazon SageMaker pre-built containers for machine learning frameworks. We discuss the core functionality, system architecture, our design principles, and lessons learned. We also describe more advanced features of AMT, such as automated early stopping and warm-starting, showing in experiments their benefits to users.


For the last two decades microfinance has become a strategy to poverty reduction by giving loans to poor people especially women. It is widespread around the world from Bangladesh, India to Bolivia and Mexico. An important feature of microfinance is that 85 per cent of its clients are females and it is considered an important tool for women empowerment. This research focuses on evaluation of the effectiveness of selected microfinance program in terms of quality of service, impact on poverty and women empowerment. Objectives of this study are to explore the reasons why microfinance is a choice of government and development planners even though evidence shows mixed results about its impacts and gender based impact assessment of microfinance programs selected from urban areas of Pakistan. In this regard, semi-structured interviews and case studies will be undertaken with selected microfinance institutions and case studies from beneficiaries will be conducted for impact assessment. Output of the proposed research includes suggestions for future policy.


"Finding Italy" explores the journey of the Romans ancestor Aeneas and his fellow Trojans from their old home, Troy, to their new country, Italy, narrated in Vergil s epic poem "Aeneid." K. F. B. Fletcher argues that a main narrative theme is patriotism, specifically the problem of how one comes to love one s new country. The various directions Aeneas receives throughout the first half of the poem are meant to create this love, explaining both to Aeneas and to Vergil s readers how they should respond to the new, unified Italy synonymous with Rome. These directions come from the gods, or from people close to Aeneas who have divine connections, and they all serve to instill an emotional connection to the land, creating a mental image of Italy that tells him far more about his destination than merely its location, and ultimately making him fall in love with Italy enough to fight for it soon after his arrival. The poem thus dramatizes the birth of nationalism, as Italy is only a concept to Aeneas throughout his trip; these directions do not describe Italy as it is at the time of Aeneas journey, but as an ideal to be realized by Aeneas and his descendants, reaching its final, perfect form under Augustus Caesar."Finding Italy" provides a very detailed reading of the directions Aeneas receives by situating them within their relevant contexts: ancient geography, Greek colonization narratives, prophecy, and ancient views of wandering. Vergil draws on all of these concepts to craft instructions that create in Aeneas an attachment to Italy before he ever arrives, a process that dramatizes a key emotional problem in the late first century BCE in the wake of the Social and Civil Wars: how to balance the love of one's modest birthplace with the love of Rome, the larger city that now encompasses it."


Book Review Classical Music: A New Way of Listening Alexander Waugh Macmillan, 1995, 144 pp., $24.95 ISBN 0-02-860446-8 (hardback) (includes a CD with excerpts and movements from 38 pieces of music) IRA BRILLIANT ALEXANDER WAUGH, A LONDON CLASSICAL RECORD PRODUCER, music writer, and critic, has produced a book for beginners which uses his own concepts to guide listeners through the world of classical music. His introduction explains his purpose: Wanting to appreciate classical music and actually having the confidence to appreciate it are, unfortunately, two different things. Everyone knows that classical music at its best is capable of moving listeners to tears, absorbing their complete attention, even changing their lives. But what is music "at its best"? How can listeners be moved to tears by what is essentially just a noise? And what is it that so wholly consumes their concentration? Classical Music: A New Way of Listening is a beginner's guide that suggests an easy new approach to the art of listening, helping you to focus on music's emotional message rather than on its technicalities. ... If classical music has not changed your life already, Classical Music: A New Way of Listening will help change it for you now. How well Waugh succeeds will depend in good measure on the validity of his claims and how they pertain to all the varieties of style found in classical music. It must be stressed that "beginner" truly characterizes the level of the book, although a more knowledgeable listener might be curious to learn about the author's "new way." It is also possible that someone might accept the principles being presented and actually enhance his or her enjoyment of the special rewards of fine music. The book's 144 pages contain illustrations on almost all the pages, a description of the orchestra and its instruments, a glossary of musical terms, a one-paragraph summary for each of forty composers, and the usual index. It leaves only a few chapters to present the essence of the concept for listening. To define what music is Waugh makes use of quotations, some insightful, some merely clever. Examples: "Music is the eye of the ear" (Thomas Drake, d. 1618); "Music is itself" (Hanslick, 1825-1904); "Music is the only sensual pleasure without vice" (Samuel Johnson, 1795-1881); "Music is the art of thinking with sounds" (Jules Combarieu, 1859-1916). There are a dozen more to entice you. His argument begins with the statement that the common element in all music is the mood that it produces. Fair enough. Then he proceeds to offer three categories, to which he assigns titles of Past, Present and Future, with the proviso that they are not to carry the usual meanings. We then are given the definitions that they are meant to bear for his purposes. "Past" refers to "music of a contemplative or reflexive nature, music that evokes nostalgia. It is usually slow and lyrical, perhaps with slow-moving harmonies, and is often played at the lower end of the instrument's range. It tends to be very melodic and frequently moves in a descending pattern" (p. 57). (Examples are Debussy's "Claire de lune," Faure's "Pavane," and the third movement of the Brahms Third Symphony.) "Present" refers to "music of an uncomplicated tone that is moving neither forward nor backward. As its name suggests, it is music of the present, a musical statement of fact - a dance or march, for instance, or the recitative of an opera. It is often used to link passages of Past and Future" (p. 57). (The first movement of Beethoven's Eighth Symphony is one of the examples here.) "Future" is "music with forward momentum that seems to be questing or moving in anticipation of some future goal. Often featuring rapidly changing harmonies, it is unsettled and not very restful, making the listener wonder where it is leading and how it will be resolved" (p. 58). (Beethoven is used for two of the three examples: the third movement of the Fifth Symphony and the last movement of the String Quartet in A Minor, Opus 132. …


Enterprise Systems (ES) are now established business operating systems in many organisations worldwide. Although the familiarity with these comprehensive systems has increased rapidly, they appear to be one of the most complex applications that organisations have ever implemented. Organisations realize the need to better leverage their knowledge resources as they lack in-house ES knowledge and the costs of engaging experienced consultants are paramount. The case study presented uses an existing framework to manage knowledge in ES and puts this into context by applying it in real-life practice. This is done through the proliferation of extended reference process models. By integrating proposed types of knowledge into process models, it will be demonstrated what types of knowledge can be captured and how this knowledge can be managed in organisations. Employees in the organisation have not only been interviewed but also encouraged to participate in capturing knowledge for their business processes. This co-operation fostered the completion of a reference model, which supports employees in managing their knowledge.


Competition in day-ahead electricity markets has been established through auctions where generators and loads bid prices and quantities. Different approaches have been discussed regarding the market auction design. Multiround auctions, despite their implementation complexity, allow market participants to adapt their successive bids to market prices considering their operational and economic constraints. However, most of the day-ahead electricity market implementations use noniterative single-round auctions. This paper presents a market simulator to compare both auction models. Different auction alternatives-such as the Spanish single-round auction that takes into account special conditions included in the generator bids and multiround auctions with different stopping rules-are analyzed. The results and acquired experience in the simulation of the Spanish market, started in January 1998, are presented. Hourly market prices; average daily price; price/demand correlation; and several economic efficiency indicators, such as generator surplus, consumer surplus, and social welfare, are compared to derive conclusions regarding the performance of the auction altematives.


Proper nutrition is a major issue all over South Asia. Here, understanding of nutrition is guided by cultural notions of substances and food products which are good for the body or not. In this section we show some of the particularities of such cultural notions.


With the rising anthropogenic emissions from human activities, elevated concentrations of air pollutants have been detected in the hemispheric air flows in recent years, aggravating the regional air pollution and deposition issues. However, the regional contributions of hemispheric air flows to deposition have been given little attention in the literature. In this light, we assess the impact of hemispheric transport on sulfur (S) and nitrogen (N) deposition for six world regions: North America (NA), Europe (EU), South Asia (SA), East Asia (EA), Middle East (ME) and Russia (RU) in 2010, by using the multi-model ensemble results from the 2nd phase of the Task Force Hemispheric Transport of Air Pollution (HTAP II) with 20 % emission perturbation experiments. About 27 %–58 %, 26 %–46 % and 12 %–23 % of local S, NOx and NH3 emissions and oxidation products are transported and removed by deposition outside of the source regions annually, with seasonal variation of 5 % more in winter and 5 % less in summer. The 20 % emission reduction in the source regions could affect 1 %–10 % of deposition in foreign continental regions and 1 %–14 % in foreign coastal regions and the open ocean. Significant influences are found from NA to the North Atlantic Ocean (2 %–14 %), and from EA to the North Pacific Ocean (4 %–10 %) and to western NA (4 %–6 %) (20 % emission reduction). The impact on deposition caused by short-distance transport between neighboring regions (i.e., from EU to RU) occurs throughout the whole year (slightly stronger in winter), while the long-range transport (i.e., from EA to NA) mainly takes place in spring and fall, which is consistent with the seasonality found for hemispheric transport of air pollutants. Deposition in the emission-intensive regions such as US, SA and EA is dominated (∼ 80 %) by own-region emissions, while deposition in the low-emission-intensity regions such as RU is almost equally affected by foreign exported emissions (40 %–60 %) and own-region emissions. We also find that deposition of the coastal regions or the near-coastal open ocean is twice more sensitive to hemispheric transport than the non-coastal continental regions, especially for regions in the downwind direction of emission sources (i.e., west coast of NA). This study highlights the significant impacts of hemispheric transport of air pollution on the deposition in coastal regions, the open ocean and low-emission-intensity regions. Further research is proposed to improve the ecosystem and human health, with regards to the enhanced hemispheric air flows. Published by Copernicus Publications on behalf of the European Geosciences Union. 12224 J. Tan et al.: Source contributions to sulfur and nitrogen deposition


The benefits of international equity portfolio diversification have been well documented. Until recently, however, most investors worldwide have concentrated exclusively on large cap names from developed countries (Ferreira and Matos [2006]; Kang and Stulz [1997]). This focus on large, often multinational companies with strong brand recognition benefited investors as they began to reduce the home-country bias within their portfolios. Unfortunately, as often happens when a market, sector, or individual company becomes widely followed, the prospective benefits to be gained–risk reduction, greater return potential, or both–have declined. Macro global factors common to developed large cap companies now explain much of their performance, while increased analyst coverage and more transparent reporting have reduced information inefficiencies (Yan [2009]). All of this has led to more highly correlated performance and lessened the magnitude of the potential benefits that investors were seeking by diversifying their portfolios away from a single country or region.


This paper estimates a quasi-structural birthweight production function using data on counties for the years 1975-1984. The analysis focuses on the effects of first trimester initiation of prenatal care, controlling for use of abortion services, cigarette smoking, birth order and income. Fixed effects model is used to control for unmeasured differences in health endowments across counties. The results indicate that early first trimester initiation of prenatal care leads to a reduction in low birthweight for both blacks and whites. Differences in use of prenatal care by race explain only a small part of the black-white differences in the fraction of low birthweight births.


ABSTRACT The androgen receptor (AR) is a nuclear hormone receptor superfamily member that conveys both trans repression and ligand-dependent trans-activation function. Activation of the AR by dihydrotestosterone (DHT) regulates diverse physiological functions including secondary sexual differentiation in the male and the induction of apoptosis by the JNK kinase, MEKK1. The AR is posttranslationally modified on lysine residues by acetylation and sumoylation. The histone acetylases p300 and P/CAF directly acetylate the AR in vitro at a conserved KLKK motif. To determine the functional properties governed by AR acetylation, point mutations of the KLKK motif that abrogated acetylation were engineered and examined in vitro and in vivo. The AR acetylation site point mutants showed wild-type trans repression of NF-κB, AP-1, and Sp1 activity; wild-type sumoylation in vitro; wild-type ligand binding; and ligand-induced conformational changes. However, acetylation-deficient AR mutants were selectively defective in DHT-induced trans activation of androgen-responsive reporter genes and coactivation by SRC1, Ubc9, TIP60, and p300. The AR acetylation site mutant showed 10-fold increased binding of the N-CoR corepressor compared with the AR wild type in the presence of ligand. Furthermore, histone deacetylase 1 (HDAC1) bound the AR both in vivo and in cultured cells and HDAC1 binding to the AR was disengaged in a DHT-dependent manner. MEKK1 induced AR-dependent apoptosis in prostate cancer cells. The AR acetylation mutant was defective in MEKK1-induced apoptosis, suggesting that the conserved AR acetylation site contributes to a pathway governing prostate cancer cellular survival. As AR lysine residue mutations that abrogate acetylation correlate with enhanced binding of the N-CoR repressor in cultured cells, the conserved AR motif may directly or indirectly regulate ligand-dependent corepressor disengagement and, thereby, ligand-dependent trans activation.