A GPU PROGRAM TO COMPUTE SNP-SNP INTERACTIONS IN GENOME-WIDE ASSOCIATION STUDIES by Srividya Ramakrishnan With the recent advances in the next generation sequencing technologies, short read sequences of human genome are made more accessible. Paired end sequencing of short reads is currently the most sensitive method for detecting somatic mutations that arise during tumor development. In this study, a novel approach to optimize the detection of structural variants using a new short read alignment program is presented. Pairwise interaction effects of the Single Nucleotide Polymorphisms (SNPs) have proven to uncover the underlying complex disease traits. Computing the disease risk based on the interaction effects of SNPs on a case – control study is a difficult problem. As another part of the thesis, a fast GPU program that can calculate the chi-square statistics of SNP-SNP interactions and output the significant interacting SNPs is presented. The algorithm is applied to the datasets of seven common diseases obtained from Wellcome Trust Case Control Consortium (WTCCC). The algorithm computed the significant SNP pairs much faster than the existing algorithms and also identifies 3 significant pairs associated with genes IL23R and C11orf30 which are associated with pathogenesis in the Crohns disease dataset.


Overuse of surface water and an increasing reliance on nonrenewable groundwater resources have been reported over various regions of the world, casting significant doubt on the sustainable water supply and food production met by irrigation. To assess the limitations of global water resources, numerous indicators have been developed, but they rarely consider nonrenewable water use. In addition, surface water over-abstraction is rarely assessed in the context of human and environmental water needs. Here, we perform a transient assessment of global water use over the historical period 1960–2010 as well as the future projections of 2011–2099, using a newly developed indicator: the blue water sustainability index (BlWSI). The BlWSI incorporates both nonrenewable groundwater use and nonsustainable water use that compromises environmental flow requirements. Our results reveal an increasing trend of water consumed from nonsustainable surface water and groundwater resources over the historical period (∼30%), and this increase is projected to continue further towards the end of this century (∼40%). The global amount of nonsustainable water consumption has been increasing especially since the late 1990s, despite a wetter climate and increasing water availability during this period. The BlWSI is the first tool suitable for consistently evaluating the renewability and degradation of surface water and groundwater resources as a result of human water over-abstraction.


The goals of this study were to describe and evaluate Christaller's research on regional and rural planning during World War II. His research was analyzed by identifying ideas from his pre-war studies that were basic to his war research, by piecing together theoretical perspectives from sources from 1940-1945, and by identifying links between those studies and his research on central places. It was shown that Christaller's research contributed to plans facilitating German Lebensraum policy and the objectives of Himmler's Reich Commission for the Strengthening of Germandom, that he built the conceptual and theoretical frameworks used in his war research on his earlier theories of central places, administrative regions, and rural settlement change, that he used his theoretical ideas to confront basic problems in planning and human geography, and that he offered innovative solutions including (1) generalization of his original theory by the addition of a mixed hierarchical principle, (2) development of normative systems of urban-centered administrative-planning regions both for the German Empire and in more detail for western Poland, (3) development of a model of metropolitan regions, and (4) development of a settlement system based theory of rural development.


In this paper we introduce the notion of mapping-based knowledge base (MKB) to formalize the situation where both the extensional and the intensional level of the ontology are determined by suitable mappings to a set of (relational) data sources. This allows for making the intensional level of the ontology as dynamic as traditionally the extensional level is. To do so, we resort to the meta-modeling capabilities of higher-order Description Logics, which allow us to see concepts and roles as individuals, and vice versa. The challenge in this setting is to design tractable query answering algorithms. Besides the definition of MKBs, our main result is that answering instance queries posed to MKBs expressed in Hi(DL-LiteR) can be done efficiently. In particular, we define a query rewriting technique that produces first-order (SQL) queries to be posed to the data sources.


In this work, we use a symbolic algebra package to derive a family of finite difference approximations for the biharmonic equation on a 9-point compact stencil. The solution and its first derivatives are carried as unknowns at the grid points. Dirichlet boundary conditions are thus incorporated naturally. Since the approximations use the 9-point compact stencil, no special formulas are needed near the boundaries. Both second-order and fourth-order discretizations are derived.
The fourth-order approximation produce more accurate results than the 13-point classical stencil or the commonly used system of two second-order equations coupled with the boundary condition.
The method suffers from slow convergence when classical iteration methods such as Gauss--Seidel or SOR are employed. In order to alleviate this problem we propose several multigrid techniques that exhibit grid-independent convergence and solve the biharmonic equation in a small amount of computer time. Test results from three different problems, including Stokes flow in a driven cavity, are reported.


This book reconstructs a neglected episode in the development of Confucianism, one that considerably influenced later Chinese religious thought. Material Virtue examines a set of four through first century B.C.E. Chinese texts that argue virtue has a physical correlate in the body. Based on both transmitted (e.g., the Mengzi or Mencius) and recently excavated (e.g., the Wuxing or Five Kinds of Action) texts, Material Virtue describes how the argument addresses challenges to early Chinese religious ethics in part by relying on emerging notions such as the balance of qi (pneumas) also found in natural philosophy.


Recent advances in distributed optimization have shown that Newton-type methods with proper communication compression mechanisms can guarantee fast local rates and low communication cost compared to first order methods. We discover that the communication cost of these methods can be further reduced, sometimes dramatically so, with a surprisingly simple trick: Basis Learn (BL). The idea is to transform the usual representation of the local Hessians via a change of basis in the space of matrices and apply compression tools to the new representation. To demonstrate the potential of using custom bases, we design a new Newton-type method (BL1), which reduces communication cost via both BL technique and bidirectional compression mechanism. Furthermore, we present two alternative extensions (BL2 and BL3) to partial participation to accommodate federated learning applications. We prove local linear and superlinear rates independent of the condition number. Finally, we support our claims with numerical experiments by comparing several first and second order methods.


Five distinct cDNA clones encoding four different isoforms of human prostaglandin (PG) E receptor EP3 subtype were isolated from a human kidney cDNA library. Two cDNA clones differed only in their 3'-untranslated regions. The four isoforms, tentatively named EP3-I, EP3-II, EP3-III, and EP3-IV, which were generated by alternative mRNA splicing, had identical amino acid sequences except for their different carboxyl-terminal tails. Transfection experiments revealed that all the four isoforms show high binding affinities to PGE2, PGE1, and M&B28767, an EP3-specific agonist, whereas their downstream signaling pathways are divergent. M&B28767 increased cAMP concentrations in cells expressing EP3-II and EP3-IV, whereas it inhibited forskolin-induced cAMP accumulations in cells expressing all EP3 isoforms. M&B28767 also stimulated phosphoinositide turnover in cells expressing EP3-I and EP3-II. Northern blot analysis revealed that the EP3 gene is expressed in a wide variety of human tissues. The human EP3 mRNA was present most abundantly in the kidney, pancreas, and uterus. A substantial expression was also detected in the heart, liver, skeletal muscle, small intestine, colon, prostate, ovary, and testis. Furthermore, reverse transcription-polymerase chain reaction analysis demonstrated tissue-specific expressions of the five different EP3 mRNA species. The present study suggests the presence of the multiple systems of PGE2/EP3 isoforms and leads to the better understanding of its physiological and pathophysiological implications in humans.


One of the most widely used methods in assessing the efficiency of public policies and programs for a set of units is Data Envelopment Analysis (DEA). DEA is a non-parametric method which identifies an efficiency frontier on which only the efficient Decision Making Units (DMUs) are placed, by using linear programming techniques. By applying non-parametric techniques of frontier estimation, the efficiency of a DMU can be measured by comparing it with an identified efficiency frontier. In this paper we have used DEA for evaluating the efficiency of the European structural funds allocated to finance the educational infrastructure through the Regional Operational Program 2007-2013, implemented in Romania. The output variables measure the educational performance as well as the school drop-out rate, while the focal input variable is the value of European funds. Romanian counties are considered to be the decision making units (DMUs) and our results confirm the deep disparities existing between Romanian counties concerning the efficient use of European structural funds.


Word-learning is one of the basic steps in language learning. A general traditional approach for learning new words is to keep a dictionary and use it whenever one encounters a new word. This video demonstrates Mobile Assisted Word-Learning (MAWL)[1]: an augmented reality based collaborative social-networking interface for learning new words using a smartphone. MAWL keeps track and saves all textual contexts during reading process; along with providing augmented reality-based assistance such as images, translation into native language, synonyms, antonyms, sentence usage etc.


The spontaneous aggregation of binary mixtures of lyotropic chromonic liquid crystals (LCLCs) was investigated using atomistic molecular dynamics simulations. Equimolecular binary mixtures were simulated in a highly dilute regime using three LCLC mesogens, namely, Sunset Yellow FCF (SSY), disodium cromoglycate (DSCG) and Bordeaux dye (BD). The influence of their molecular shape, conformational flexibility and hydrogen bonding capability in the formation of aggregates was studied in detail. Stacking distance comparison, hydrogen bond distribution analysis and solvent accessible surface area calculations were performed along with molecular visualization. The mixtures exhibited three different molecular segregation modes where the number of mixed π–π stacks was minimized. Aggregation of chromonic binary mixtures depends strongly on mesogen cross-sectional area differences. However, the distribution of LCLC solubilizing groups and their H-bonding density formed around mixed stacks contributed significantly to achieving different mixture segregation patterns. Average stacking distances between π–π interactions were consistently seen to be around 0.34 nm. Mesogens with similar long axis molecular length and high hydrogen bonding capacity represent a likely choice for the preparation of chromonic binary mixtures. These findings contribute to the understanding of general aggregation rules for chromonic mesophases which are required for the design of novel chromonic supramolecular applications.


We reported a case report of mass-like cecum and ascending colon carcinoma featuring exophytic cavity growth. The external lump size was about 84 mm × 72 mm that violated right-side illiopsoas and psoas major muscles. Preoperative CT diagnosis was performed to confirm a retroperitoneal cancer involving right hemicolon, psoas major and casiliopsoas muscles. Mesenchymoma was the paramount consideration. Besides, right hemicolon excision and involved psoas major excision were performed during operation. The postoperation pathology showed that colon cancer has involved iliopsoas and psoas major muscles. Above all, the patients recovered well after operation.


The Great Lakes and their connecting channels form the largest fresh surface water system on earth. Over the past 10 years, focus on environmental monitoring has shifted to an array of recently discovered compounds known as 'chemicals of emerging concern' (CEC). These chemicals are found in products used daily in households, businesses, agriculture and industry, such as flame retardants, pharmaceuticals, personal care products, and pesticides. Wastewater treatment plants are among the important pathways by which CEC enter the Great Lakes, with concentrations highest in the vicinity of wastewater discharges. Treated sewage is often discharged into the nearshore waters, which also provide a source of drinking water to the public. In 2009–2011, the International Joint Commission addressed the need to assess the effectiveness of existing wastewater treatment technologies in the basin to remove CEC, as well as to gain insight on potential advanced technologies to improve their removal. This assessment encompassed three major activities, development of an inventory of municipal wastewater treatment plants that discharge in the basin; a survey of detailed operational data for selected wastewater facilities; and a comprehensive literature review and analysis of the effectiveness of various wastewater treatment technologies to remove chemicals of emerging concern.


Based on the real life of Edith Warner, who ran a tearoom at Otowi Crossing, just below Los Alamos, The Woman at Otowi Crossing is the story of Helen Chalmer, a person in tune with her adopted environment and her neighbors in the nearby Indian pueblo and also a friend of the first atomic scientists. The secret evolution of atomic research is a counterpoint to her psychic development. In keeping with its tradition of allowing the best of its list to thrive, Ohio University Press/Swallow Press is particularly proud to reissue The Woman at Otowi Crossing by best-selling author Frank Waters. This new edition features an introduction by Professor Thomas J. Lyon and a foreword by the author's widow, Barbara Waters. The story is quintessential Waters: a parable for the potentially destructive materialism of the mid-twentieth century. The antidote is Helen Chalmer's ability to understand a deeper truth of her being; beyond the Western notion of selfhood, beyond the sense of a personality distinct from the rest, she experiences a new and wider awareness. The basis for an opera of the same name, The Woman at Otowi Crossing is the powerful story of the crossing of cultures and lives: a fable for our times.


The presence of cochlear-based compression at low frequencies was investigated by measuring phase effects in harmonic maskers. In normal-hearing listeners, the amount of masking produced depends strongly on the phase relationships between the individual masker components. This effect is thought to be determined primarily by properties of the cochlea, including the phase dispersion and compressive input-output function of the basilar membrane. Thresholds for signals of 250 and 1000 Hz were measured in harmonic maskers with fundamental frequencies of 12.5 and 100 Hz as a function of the masker phase curvature. Results from 12 listeners with sensorineural hearing loss showed reduced masker phase effects, when compared with data from normal-hearing listeners, at both 250- and 1000-Hz signal frequencies. The effects of hearing impairment on phase-related masking differences were not well simulated in normal-hearing listeners by an additive white noise, suggesting that the effects of hearing impairment are not simply due to reduced sensation level. Maximum differences in masked threshold were correlated with auditory filter bandwidths at the respective frequencies, suggesting that both measures are affected by a common underlying mechanism, presumably related to cochlear outer hair cell function. The results also suggest that normal peripheral compression remains strong even at 250 Hz.


Personal jurisdiction doctrine as articulated by the Supreme Court is in disarray. As a constitutional doctrine whose contours remain imprecise, the law of personal jurisdiction has generated confusion, unpredictability, and extensive satellite litigation over what should be an uncomplicated preliminary issue. Many commentators have long lamented these defects, making suggestions for how the doctrine could be improved. Although many of these proposals have had much to offer, they generally have failed to articulate (or adequately justify or explain) a simple and sound approach to jurisdiction that the Supreme Court can embrace. This Article revises the law of personal jurisdiction by reconceiving the proper role of due process within the doctrine - which is to ensure that defendants receive adequate notice of an action and are protected against arbitrary assertions of governmental power - and reasserting the role of state sovereignty and interstate federalism as concepts that permit jurisdiction over all disputes in which a state has a legitimate interest. The doctrines of venue and forum non conveniens are left to redress any meaningful burdens on defendants arising out of having to litigate in inconvenient fora. The result is a coherent analysis that will provide litigants and courts clear guidance regarding the scope of a court's jurisdiction to adjudicate.


An empirical formula for gamma-ray buildup factors in two-layer shields is proposed. The values of the parameters are given for the formula when fitted to the dose buildup factors, calculated by the invariant imbedding method, for normally incident gamma rays penetrating two-layer shields comprised of combinations of water, iron, or lead slabs. The results from the present formula are in excellent agreement with the basic data in the 0.66- to 10-MeV energy range and for total thicknesses up to about20 mfp. The parameters used in the formula change smoothly with the source energy. Therefore, the buildup factor for any arbitrary energy can easily be estimated by interpolation of the parameters with respect to energy. The buildup factors provided by this formula also are in good agreement with those from transport calculations for two-layer shields consisting of water and lead. These factors also agree with those measured by two ionization chambers for /sup 60/Co radiation penetrating two-layer shields comprised of water, iron, or lead slabs.


The deluge of scientific research data has excited the general public, as well as the scientific community, with the possibilities for better understanding of scientific problems, from climate to culture. For data to be available, researchers must be willing and able to share them. The policies of governments, funding agencies, journals, and university tenure and promotion committees also influence how, when, and whether research data are shared. Data are complex objects. Their purposes and the methods by which they are produced vary widely across scientific fields, as do the criteria for sharing them. To address these challenges, it is necessary to examine the arguments for sharing data and how those arguments match the motivations and interests of the scientific community and the public. Four arguments are examined: to make the results of publicly funded data available to the public, to enable others to ask new questions of extant data, to advance the state of science, and to reproduce research. Libraries need to consider their role in the face of each of these arguments, and what expertise and systems they require for data curation.


The Zhang-Markusen (ZM) theory hypothesizes an inverse U-shaped relationship between human capital and foreign direct investment (FDI). Therefore, low wage countries with low human capital cannot attract FDI. To test this hypothesis, we regress FDI on educational levels across countries while grouping them in different income cohorts. Our findings partly support ZM. Rich countries with high human capital and poor countries with low human capital demonstrate an inverse correlation between FDI and human capital proxies. However, for middle-income and upper middle-income countries, human capital (especially tertiary education) has a positive relationship with FDI.


Stadium-construction projects are costly and affect the community—positively and negatively. At urban universities, these impacts extend beyond campuses into the broader community. Thus, athletic-department communication about the value of stadium projects to a diverse group of stakeholders becomes important. Following stakeholder theory, the purpose of the study was to investigate social-media messages disseminated by an urban university engaged in a stadium-redevelopment project (Georgia State University [GSU]) and the public response. A content analysis of Facebook and Twitter posts by GSU (N = 39) and the public response (N = 359) yielded 8 themes: a focus on athletics, a focus on university, informing about urban community development impact, explaining capital project funding source, maintaining the stadium legacy, promoting public–private partnerships, and understanding effects on transit. Findings support previous literature that organizational communication reflects organizational priorities.


Cancer deaths are primarily caused by metastases, not by the parent tumor. However, the physical-chemical mechanisms and parameters within the cellular micro-environment that initiate the onset of metastasis, are not understood. Here we show that human colon carcinoma (HCT-8) cells can exhibit a dissociative, metastasislike phenotype (MLP) in vitro when cultured on substrates with appropriate mechanical stiffness, physiologically relevant 21 kPa47 kPa, but not on very soft (1 kPa) and very stiff (3.6 GPa) substrates. The cell-cell adhesion molecule E-Cadherin, a metastasis hallmark, decreases 4.73 ± 1.43 times on cell membranes in concert with disassociation. Both specific and non-specific cell adhesion decrease once the cells have disassociated. After reculturing the disassociated cells on fresh substrates, they retain the disassociated phenotype regardless of substrate stiffness. Inducing E-Cadherin overexpression in MLP cells only partially reverses the MLP phenotype in a minority population of the dissociated cells. Traction Force Microscopy reveals that after dissociation, HCT-8 cells exert weaker traction force (~100 Pa) on substrates than they do prior to dissociation (~250 Pa). Our results indicate, during culture on the appropriate mechanical microenvironment, HCT-8 cells undergo a stable cell-state transition with increased in vitro metastasis-like characteristics as compared to parent cells grown on standard, very stiff tissue culture dishes. This novel finding suggests that the onset of metastasis may, in part, be linked to the intracellular forces and the mechanical microenvironment of the tumor.


The fiscal and educational consequences of charter expansion for non-charter students are central issues in the debate over charter schools. Do charter schools drain resources and high-achieving peers from non-charter schools? This paper answers these questions using an empirical strategy that exploits a 2011 reform that lifted caps on charter schools for underperforming districts in Massachusetts. We use complementary synthetic control instrumental variables (IV-SC) and differences-in-differences instrumental variables (IV-DiD) estimators. The results suggest greater charter attendance increases per-pupil expenditures in traditional public schools and induces them to shift expenditure from support services to instruction and salaries. At the same time, charter expansion has a small positive effect on non-charter students' achievement.


The goal of this study was to test cross-cultural/cross-national differences in the association between coworker interpersonal justice and coworker conflict and the implications of such differences for employee effectiveness. Harmony is a central value in China but is less important in the United States, and the individual value of harmony may influence Chinese and US employees differently in their response to low levels of coworker interpersonal justice. We collected data from employees and their coworkers in China (214 dyads) and the US (301 dyads). There were three major findings. First, coworker interpersonal justice was negatively related to coworker conflict. Second, coworker conflict significantly mediated coworker interpersonal justice in relation to the employee effectiveness variables of task performance, organisational citizenship behaviours, and counterproductive work behaviours. Finally, in the Chinese sample, harmony significantly buffered the indirect effect of coworker interpersonal justice on employee effectiveness via coworker conflict, whereas in the US sample, harmony significantly intensified the indirect effect of coworker interpersonal justice on employee effectiveness via coworker conflict.


This dissertation has focused on topics in statistical signal processing including detection and estimation theory, information fusion, model order selection, as well as their applications to standoff detection. Model order selection is a very common problem in statistical signal processing. In composite multiple hypothesis testing, the maximum likelihood rule will always choose the hypothesis with the largest order if the parameters in each candidate hypothesis are hierarchically nested. Hence, many methods have been proposed to offset this overestimating tendency by introducing a penalty term. Two popular methods are the minimum description length (MDL) and the Akaike information criterion (AIC). It has been shown that the MDL is consistent and the AIC tends to overestimate the model as the sample size goes to infinity. In this dissertation, we show that for a fixed sample size, the MDL and the AIC are inconsistent as the noise variance goes to zero. The result is surprising since intuitively, a good model order selection criterion should choose the correct model when the noise is small enough. Moreover, it is proved that the embedded exponentially family (EEF) criterion is consistent as the noise variance goes to zero. Standoff detection aims to detect hazardous substances in an effort to keep people away from potential damage and danger. The work in standoff detection has been on developing algorithms for detection and classification of surface chemical agents using Raman spectra. We use an autoregressive model to fit the Raman spectra, develop an unsupervised detection algorithm followed by a classification scheme, and manage to control the false alarm rate to a low level while maintaining a very good detection and classification performance. In information fusion and sensor integration,multiple sensors of the same or different types are deployed in order to obtain more information to make a better decision than with a single sensor. A common and simple method is to assume that the measurements of the sensors are independent, so that the joint probability density function (PDF) is the product of the marginal PDFs. However, this assumption does not hold if the measurements are correlated. We have proposed a novel method of constructing the joint PDF using the exponential family. This method combines all the available information in a multi-sensor setting from a statistical standpoint. It is shown that this method is asymptotically optimal in minimizing Kullback-Leibler divergence, and it attains comparable detection/classification performance as existing methods. The maximum likelihood estimator (MLE) is the most popular method in parameter estimation. It is asymptotically optimal in that it approximates the minimum variance unbiased (MVU) estimator for large data records. Under a misspecified model, it is well known that the MLE still converges to a well defined limit as the sample size goes to infinity. We have proved that under some regularity conditions, the MLE under a misspecified model also converges to a well defined limit at high signal-to-noise ratio (SNR). This result provides important performance analysis of the MLE under a misspecified model.


An antiserum was generated against a dodecapeptide whose sequence is found at the C-terminus of a cyclic AMP (cAMP)-specific, type-IVA phosphodiesterase encoded by the rat 'dunc-like' cyclic AMP phosphodiesterase (RD1) cDNA. This antiserum identified a single approximately 73 kDa protein species upon immunoblotting of cerebellum homogenates. This species co-migrated upon SDS/PAGE with a single immunoreactive species observed in COS cells transfected with the cDNA for RD1. Native RD1 in cerebellum was found to be predominantly (approximately 93%) membrane-associated and could be found in isolated synaptosome populations, in particular those enriched in post-synaptic densities. Fractionation of lysed synaptosomes on sucrose density gradients identified RD1 as co-migrating with the plasma membrane marker 5'-nucleotidase. Laser scanning confocal and digital deconvolution immunofluorescence studies done on intact COS cells transfected with RD1 cDNA showed RD1 to be predominantly localized to plasma membranes but also associated with the Golgi apparatus and intracellular vesicles. RD1-specific antisera immunoprecipitated phosphodiesterase activity from solubilized cerebellum membranes. This activity had the characteristics expected of the type-IV cAMP phosphodiesterase RD1 in that it was cAMP specific, exhibited a low Km cAMP of 2.3 microM, high sensitivity to inhibition by 4-[3-(cyclopentoxyl)-4-methoxyphenyl]-2-pyrrolidone (rolipram) (Ki approximately 0.7 microM) and was unaffected by Ca2+/calmodulin and low concentrations of cyclic GMP. The phosphodiesterase activities of RD1 solubilized from both cerebellum and transfected COS cell membranes showed identical first-order thermal denaturation kinetics at 50 degrees C. Native RD1 from cerebellum was shown to be an integral protein in that it was solubilized using the non-ionic detergent Triton X-100 but not by either re-homogenization or high NaCl concentrations. The observation that hydroxylamine was unable to cause the release of RD1 from either cerebellum or COS membranes and that [3H]palmitate was not incorporated into the RD1 protein immunoprecipitated from COS cells transfected with RD1 cDNA, indicated that RD1 was not anchored by N-terminal acylation. The engineered deletion of the 25 residues forming the unique N-terminal domain of RD1 caused both a profound increase in its activity (approximately 2-fold increase in Vmax) and a profound change in intracellular distribution. Thus, immunofluorescence studies identified the N-terminal truncated species as occurring exclusively ion the cytosol of transfected COS cells. The cDNA for RD1 thus appears to encode a native full-length type-IVA phosphodiesterase that is expressed in cerebellum.(ABSTRACT TRUNCATED AT 400 WORDS)


This dissertation discusses topics related to the performance and long-term durability of glassreinforced composites. The first portion of this dissertation describes work to assess the effect that post-curing has on widely used E-glass/vinyl-ester composites (E-glass/Derakane 510-A and E-glass/Derakane 8084). It is shown that post-curing can have significant positive effects on the initial material properties of glass-reinforced vinyl ester composites. Furthermore, the post-cure of 82oC for four hours stabilizes the matrix, and as such reduces matrix-related material property evolution. By stopping or nearly stopping material property evolution due to matrix curing over time, the post-cure regime isolates and allows the study of other time-dependent effects, such as fatigue or hygrothermal degradation, and aids designers by establishing an unchanging base set of initial (undamaged) material design properties. The second portion of this dissertation discusses the effects that mean stress and R-ratio have on the fatigue performance of the same material. Qualitative and quantitative differences are seen in the performance as a function of the loading ratio. A residual strength based life prediction model developed at Virginia Tech is applied to the fatigue data, characterizing the material under constant-amplitude loading. Three curve-fitting parameters are then used along with the model to predict variable-amplitude fatigue lives, with remarkably good results. The final portion of the dissertation concerns the effect of hygrothermal and accelerated aging on glass-reinforced composites. A meta-study is performed on data from the literature, and a glassdegradation-based life-prediction model is applied to the data. It is seen that a static fatiguebased activation energy approach to residual strength can predict activation energies associated with glass-reinforced composite strength degradation in the case of glass-reinforced concrete quite well, predicting values of 80-100 kJ/mol, which are similar to those expected for glass dissolution via silica ring opening. The model may also hold some promise for doing the same for glass-reinforced polymer composites.


Abstract This minireview focuses on the anti-nicotinic properties of bupropion (BP) at the molecular and cellular levels. The main pharmacological mechanism is based on the fact that BP induces the release as well as inhibits the reuptake of neurotransmitters such as a dopamine (DA) and norepinephrine (NE). Additional mechanisms of action have been also determined. For example, BP is a noncompetitive antagonist (NCA) of several nicotinic acetylcholine receptors (AChRs). Based on this evidence, the clinical activity of BP is currently considered to be mediated by its stimulatory action on the DA and NE systems as well as its inhibitory action on AChRs. More specifically, BP inhibits presynaptic α4β2-containing AChRs in GABAergic neurons of the ventral tegmental area and α3β4-containing AChRs in the habenulo-intrerpeduncular pathway. This inhibition finally decreases the addictive effects mediated by nicotine. Based on studies on muscle AChRs at the molecular level, a sequential mechanism is hypothesized to explain the inhibitory action of BP on neuronal AChRs: (1) BP first binds to AChRs in the resting state, decreasing the probability of ion channel opening, (2) the remnant fraction of open ion channels is subsequently decreased by accelerating the desensitization process, and (3), BP interacts with a binding domain located between the serine (position 6') and valine (position 13') rings that is shared with other NCAs including, phencyclidine, tricyclic antidepressants, and serotonin selective reuptake inhibitors. This new evidence paves the way for further investigations using AChRs as targets for the action of safer antidepressants and novel anti-addictive compounds.


The ability of artificial characters to express emotions is essential for the natural interaction with humans. Their absence could be interpreted as coldness towards the user. Artificial characters can have different embodiments. Screen characters and robotic characters are currently among the most widely used. This study investigates the influence of the character's embodiment on how users perceive the character's emotional expressions. The results show that there is no significant difference in the perceived intensity and recognition accuracy between a robotic character and a screen character. Another important aspect of the character is its ability to express different emotional intensity levels. Developers create different geometrical intensity levels of emotional expressions by equally dividing the spatial difference of each facial component between the neutral and maximum expression. However, the relationship between this geometrical intensity and the intensity perceived by the user might not be strictly linear. This study shows that also a quadratic trend is present in this relationship and that10% steps increase of geometrical intensity can often be distinguished whereas 20% steps can be distinguished almost all the time.


Quantitative error analyses for the simulation of wave propagation in three-dimensional random media, when narrow angular scattering is assumed, are presented for plane-wave and spherical-wave geometry. This includes the errors that result from finite grid size, finite simulation dimensions, and the separation of the two-dimensional screens along the propagation direction. Simple error scalings are determined for power-law spectra of the random refractive indices of the media. The effects of a finite inner scale are also considered. The spatial spectra of the intensity errors are calculated and compared with the spatial spectra of intensity. The numerical requirements for a simulation of given accuracy are determined for realizations of the field. The numerical requirements for accurate estimation of higher moments of the field are less stringent.


This article explores how the courts of the early Republic interpreted the Anti-Injunction Act ("AIA") of 1793 as applied to federal bankruptcy injunctions restraining state-court proceedings — a common and indeed intrinsic constitutional feature of federal bankruptcy proceedings pursuant to any "uniform Law on the subject of Bankruptcies." The early-Republic bankruptcy injunction cases provide indirect support for James Pfander's and Nassim Nazemi's novel original-ancillary theory positing a much more limited scope for the 1793 AIA than do conventional accounts of that statute's bar. According to Pfander and Nazemi, the 1793 AIA's prohibition against "writs of injunctions" to stay state-court proceedings (sought via an original bill through a suit in equity) did not prohibit ancillary relief in the nature of an injunction (sought via a motion or petition) granted in an equitable proceeding principally seeking relief other than or independent of such an injunction, but for which an injunctive decree (not via a "writ of injunction") might nonetheless be necessary or appropriate. The original-ancillary distinction identified by Pfander and Nazemi is reflected in one of the most prominent, fundamental, and longstanding jurisdictional and procedural divides with respect to bankruptcy proceedings — the dichotomy between plenary assignee/trustee suits at law or in equity via an original complaint or bill, as distinguished from so-called summary bankruptcy proceedings in equity on motion or petition. Early, influential decisions of Justice Story established that federal bankruptcy injunctions properly issue in ancillary summary proceedings and (consistent with the Pfander-Nazemi original-ancillary theory) found no obstacle in the 1793 AIA to enjoining state-court proceedings thereby.The bankruptcy cases not only help illustrate that the 1793 AIA had a much more limited scope than has generally been acknowledged (consistent with both the Pfander-Nazemi original-ancillary interpretation and William Mayton's single-justice interpretation), they also illuminate the central importance of the AIA, nonetheless, in assuaging federalism sensitivities that were easily aroused in the early Republic. Indeed, the federal courts' administration of nineteenth century bankruptcy laws produced a very acrimonious standoff involving U.S. Supreme Court Justice Joseph Story, New Hampshire Supreme Court Justice Joel Parker, and the New Hampshire legislature, and bearing striking similarities to the Morris v. Allen controversy that many posit as the impetus for enactment of the 1793 AIA. Tellingly, the U.S. Supreme Court ultimately diffused that bankruptcy controversy through a very nuanced invocation of the 1793 AIA that neither broadened its reach (beyond that posited by Pfander and Nazemi) nor posed any enduring obstacle to the effectiveness of federal bankruptcy laws.


Congregations as Systems for Empowering Missional Leadership: A Lutheran Hermeneutic for Leading in Mission by Terri Lynn Martinson Elton What are the cultural dynamics within a congregational system that are vital to the empowering of missional leadership? Do Lutherans have anything to contribute to the missional church movement in the United States? These two questions were primary for this dissertation and emerged out of two gaps identified in the missional church literature. Seeing congregations as complex, open systems, missional leadership within congregational systems was studied using a grounded theory, qualitative research approach. The five ELCA congregational systems in this study were identified by their peers as excelling in helping their faith community discover their calling as disciples of Jesus and empowering them to live their faith in the world. They were studied using primarily the ethnographic methods of field observation, focus groups, and journaling. The particular cultural dynamics of each congregational system were identified first, and then those that were common among them were articulated. These eight common cultural dynamics included: an active view of God, the world as the horizon, discipleship as a way of life, congregational systems as a network of people, the dance of leadership, tension of ministry and mission, a vibrant Lutheran identity, and a changing and adapting posture. From these cultural dynamics, a Lutheran hermeneutic for leading in mission was proposed. Using Craig Van Gelder's four part hermeneutic, this proposal was shaped around: communicatively discerned, biblically and theologically framed, theoretically ii R eproduced with perm ission of the copyright owner. Further reproduction prohibited without perm ission. informed, and strategic action. The foundation of this hermeneutic of leading in mission was a missional theology, with a missional view of God, church, and ministry tied to a missional, Lutheran understanding of baptism and vocation. To this foundation were added several theoretical perspectives: grounded theory; ethnography; cultural anthropology; complex, open systems theory; and organizational leadership theory. The qualitative, grounded theory research findings, having sought to capture the what and why of the faith communities with a missiological inquiry of discovering God's intent, were woven throughout. The addition of qualitative research provided the opportunity for the lived experiences of missional congregational systems to speak into the missional church conversation in the United States offering a Lutheran voice, while also keeping theology


How are international law firms faring in China? Drawing on 2013 data, this article presents the first comprehensive overview of the field, including information about the global mix of players and variation in market niche. Three variables—years present in China, global strategy, and level of localization—help explain why some China practices grow bigger than others. Overall, however, there is a great deal of convergence on one business model: an outpost office with a median size of eleven lawyers responsible for under 5 percent of worldwide revenue. The common experience of stagnation following market entry illustrates the strength of hype, the constraints of partnership, and the persistent power of the Chinese state to shape the legal services market. At the same time, the rarity of market exit reflects perceptions that a China presence is a valuable symbol of global commitment and a worthwhile bet on future growth.


Many plants experience freezing temperatures that can be damaging and even lethal. Current climate projections suggest that freezing events are likely to increase in early autumn and late spring, at times when plants are unprepared to deal with them. Previous literature has highlighted specific mechanical properties of the plant cell wall that may impact upon freezing tolerance. For example, the limiting pore size of the cell wall can influence ice nucleation and growth, whilst cell-wall stiffness can alleviate damage from freeze-induce dehydration. More recently, there is increasing evidence that the wall undergoes major modifications in order to prepare for freezing stress, with the observation that cellwall thickness increases and differential regulation of genes encoding cell-wall modifying enzymes occurs after exposure to cold temperatures. These findings suggest that cell-wall structure or composition are necessary and contribute to plant freezing tolerance. With the advent of molecular genetic techniques, we can now explore in further detail what aspects of the cell wall are important to prevent freezing damage, and identify targets to develop plants with enhanced freezing tolerance in the future.


Accurate determination of tumour size in lung adenocarcinoma with bronchoalveolar features (BAC) is important for the determination of TNM (tumour, nodes, metastasis) scores used in staging, prognosis and therapy response assessment. However, tumour sizes derived using lung window (LW) CT or soft-tissue/mediastinal window (MW) CT often give different results. This study examines which measurement correlates best with actual tumour size and which best identifies advanced disease. This retrospective study included 43 BAC patients who underwent surgical resection with mediastinal lymphadenectomy <4 weeks post CT scan. The largest unidimensional tumour diameter on each CT window was compared with actual histopathological tumour size (HP). LW, MW and HP size measurements and a recently described CT parameter - the modified tumour shadow disappearance rate (mTDR) = (1 - [MW/LW]) - were then used to determine which parameter best discriminated between the presence or absence of advanced disease. There was no difference between HP and LW sizes, but MW significantly underestimated HP size (p<0.0001). Unlike MW (p = 0.01) and mTDR (p = 0.001), neither HP (p = 0.14) nor LW (p = 0.10) distinguished between patients with or without advanced disease. On receiver operating characteristic (ROC) analysis at a cut-off of ≤0.13, the sensitivity and specificity of mTDR for detecting advanced disease were 69% and 89%, respectively. In patients with tumours ≤3 cm, only mTDR remained a significant predictor of advanced disease (p = 0.017), with best cut-off at ≤0.20, giving a sensitivity and specificity of 71% and 94%, respectively. MW better predicts advanced disease than LW and might also need to be recorded for RECIST (response evaluation criteria in solid tumours) assessment for T staging of BAC; however, mTDR appears to be an even better predictor and should also be used.


Marine energy in the United Kingdom is undergoing a period of growth in terms of development and implementation. The current installed tidal energy capacity is expected to rise to provide 20% of the United Kingdom's electricity demand by 2050. This article used life cycle assessment to study four tidal energy devices, comparing their embodied energy and carbon dioxide emissions. The device designs studied included a multi-blade turbine, two three-blade horizontal axis turbine machines and an Archimedes' screw device. These machines were chosen to represent a cross section of design for the device, foundation, installation and operation. Embodied energy was considered over the lifetime of each device. Energy use from fabrication, transport, installation, maintenance, decommissioning and recycling was all calculated and compared to the energy generated by each device. Finally, the embodied energy, CO2 intensity and energy payback periods were compared to those of conventional power generating systems and other renewable energy sources. Devices were studied based on a functional unit, defined as a 10 MW array installed for 100 years. Of the devices studied, the OpenHydro Open Centre turbine was found to have the best ratio of generated to embodied energy. All devices achieved CO2 and energy payback within 12 years and exhibited CO2 intensity between 18 and 35 gCO2/kW h. This compares favourably against current energy sources such as wind (8–12 gCO2/kW h), solar photovoltaic (~30 gCO2/kW h), nuclear (~70 gCO2/kW h) and coal (~1000 gCO2/kW h).


We determine the core characteristics of a climate coalition's optimal policies in a dynamic two country directed technical change framework. Unilateral policies alter the structure of production and thereby innovation incentives across countries. Whenever feasible, optimal policies implement sustainable growth by directing global innovation to the nonpolluting sector. If nonparticipants drive global innovation, this requires policies relocating clean production to nonparticipants. A calibration exercise suggests that the US or EU alone are too small to implement sustainable growth. A coalition of Annex I countries that signed the Kyoto protocol can implement sustainable growth, yet required tax rates are very high.


Caribbean governments need to make significant investments in high quality infrastructure assets. Public-Private Partnerships (PPPs) offer a mechanism for governments to procure, finance and implement public infrastructure projects that can leverage the private sector's knowledge, financial capacity and efficiency. The implementation of PPPs requires careful risk management and mitigation, as these long-term contracts are complex to structure, and require specific knowledge and experience. Building up technical capacity, especially of government officials who oversee PPP transactions, is therefore essential. Several features of the Caribbean economic environment such as small market size, shared legal and regulatory systems, capacity constraints within governments, high investment needs and limited fiscal space deserve special treatment.
This Toolkit describes the Regional environment for PPPs, drawing lessons from global as well as Caribbean examples, and includes a Model Caribbean PPP Policy Template. The six Toolkit modules cover the key aspects of PPPs, including policy and enabling environment, project identification and screening, development of the business case, procurement and contract monitoring.


Recent papers on the theory of representation learning has shown the importance of a quantity called diversity when generalizing from a set of source tasks to a target task. Most of these papers assume that the function mapping shared representations to predictions is linear, for both source and target tasks. In practice, researchers in deep learning use different numbers of extra layers following the pretrained model based on the difficulty of the new task. This motivates us to ask whether diversity can be achieved when source tasks and the target task use different prediction function spaces beyond linear functions. We show that diversity holds even if the target task uses a neural network with multiple layers, as long as source tasks use linear functions. If source tasks use nonlinear prediction functions, we provide a negative result by showing that depth-1 neural networks with ReLu activation function need exponentially many source tasks to achieve diversity. For a general function class, we find that eluder dimension gives a lower bound on the number of tasks required for diversity. Our theoretical results imply that simpler tasks generalize better. Though our theoretical results are shown for the global minimizer of empirical risks, their qualitative predictions still hold true for gradient-based optimization algorithms as verified by our simulations on deep neural networks.


Internet services are more necessary part of our daily life. We rely growingly on the ease and flexibility of Internet connected devices to shop, communicate and in general perform tasks that would require our physical presence. While very valuable, Internet transactions can represent user sensitive information. Banking sector's and personal medical records, system authorization passwords and personal communication records can easily become known to an enemy who can easily compromise any of the devices include in online transactions. Regrettably, In this transaction the user's personal computer seems to be the weakest link. At the same time attacker also use new attacks for identification of user's sensitive information with vulnerabilities that use a small part of code in web pages. Overcome these problems use a novel approach for a filtering technique to finding malicious web pages very effectively and efficiently using supervised machine learning. Also detailed study some other techniques researcher research to analysis and detection of malicious web pages. Keywords— Malicious web page analysis, driveby download exploits, efficient web page filtering.


This article explores the evolution of capital flows to emerging markets over the last 30 years with emphasis on the past decade. Capital markets in emerging-market economies have evolved substantially over the period, becoming increasingly deep and resilient. The author looks at how capital flows to these countries have changed in terms of magnitude, geographical distribution, the financial instruments used, and the country of origin. He also examines how changes in the investor base have affected these flows and reviews the factors underlying the growth of private capital flows in the 1990s.


According to Carruthers' (2006) massive modularity (MM) thesis, the central systems of the mind are widely encapsulated and operate via heuristics and approximation techniques similar to those found in computer science. It follows from this, he claims, that widely encapsulated central systems are feasibly tractable. I argue that insofar as Carruthers uses this weakened definition of encapsulation, his thesis faces a dilemma: either is a misnomer (Prinz, 2006) and therefore unrecognisable as a version of MM, or it isn't, and must put forward a convincing version of MM (Samuels, 2006). I claim that Carruthers' commitment to this claim about central systems meets this challenge by adopting an understanding of central systems whose information-frugal and processing-frugal operations allow for feasible tractability. I conclude that the CWT provides a plausible and distinctive account of MM.


Abstract An inspection game is a mathematical model of a non‐cooperative situation where an inspector verifies that another party, called inspectee, adheres to legal rules. The inspector wishes to deter illegal activity on the part of the inspectee and, should illegal activity nevertheless take place, detect it with the highest possible probability and as soon as possible. The inspectee may have some incentive to violate his commitments and violation, if observed, will incur punishment. Therefore if he chooses illegal behaviour, the inspectee will wish to avoid detection with the highest possible probability. Three examples of applications are presented. The first one deals with random controls in public transportation systems. The second one describes the problem of verification of arms control and disarmament in a very general way. The third one deals with inspections over time which are important in the context of non‐proliferation verification.


Cadmium (Cd) is present in all soils, usually as a trace constituent, but it can reach higher levels in agricultural soils. Cd can then be absorbed by plants and become a potential risk to human health. Once taken up by a plant, there are mechanisms for heavy metal detoxification in the plant. Here, a cadmium-tolerant and a cadmium-sensitive rice cultivars were grown hydroponically to investigate the effects of cadmium (Cd) applied at low levels on uptake and transport, subcellular distribution and binding forms of Cd in rice plants. Our results showed that increasing the Cd treatment from 1.0 μM to 5.0 μM Cd increased the shoot Cd content by 55% in the cadmium-tolerant cultivar, and by 108% in the cadmium-sensitive cultivar. For the cadmium-tolerant cultivar, increasing Cd treatment from 1.0 μM to 5.0 μM increased the root Cd content by 116%, whereas for the cadmium-sensitive cultivar, increasing Cd treatment from 1.0 μM to 5.0 μM increased the root Cd content by 80%. Further, the ratio of Cd accumulation in shoots over roots decreased from 0.19 to 0.14 in the cadmium-tolerant cultivar, while it increased from 0.20 to 0.26 in the cadmium-sensitive cultivar, showing that the transportation ability for Cd was different between the two tested rice cultivars. At the higher Cd level of 5.0 μM, most of the Cd in the plants was localized in cell walls and vacuoles in both cultivars, whereas small portions of Cd were distributed in the cytoplasm, suggesting that the important metabolic and physiological processes were not impaired under Cd stress. Furthermore, the major portions of Cd in the cells were combined with organic acids, proteins and polysaccharide, and were consequently detoxified. The difference in the distribution of cadmium in rice plants resulted in the difference in Cd tolerance between the two rice cultivars used. It can be concluded that the retention of Cd in root cell walls, compartmentation of Cd into vacuoles and the suppressed transportation of Cd from roots to shoots are the most important mechanisms involved in the detoxification of Cd in rice plants.


Interfraternity Motor Sweepstakes—which would come to be known colloquially as Buggy—is one of Carnegie Mellon University's longest traditions. The students and alumni who have participated throughout the years, documented so much of its history, and celebrated across generations created a community that is rare on modern university campuses.But the Sweepstakes demonstrated—and continues to demonstrate—a profoundly unique aspect of CMU's community. Buggy is a demonstration of our collective commitment to both art and science. It's a demonstration of our desire to create applied knowledge to solve problems that exist outside the walls of the university. This is what makes CMU great: our ability to be interdisciplinary, to seek non-traditional solutions to problems, and to empower our students to challenge themselves outside of the classroom. It's this spirit that made Spring Carnival—where the Sweepstakes happen—as important to CMU's culture today as it was one-hundred years ago. This is our celebration of a collaboration between the arts, the sciences, the humanities, and athletics. This is our celebration of a collaboration between students, faculty, staff, alumni, and the larger world. This is where we celebrate working together toward a common goal.And Buggy—a student-run event—was the first, and most enduring, demonstration of all of those ideals. Nuts, Bolts, & Wheels: 100 Years of Buggy is a celebration of those students—past, present, and future.


It's testable. It's light-weight. It's open-source. It's . . . Microsoft? Yes, finally, Microsoft has figured it out. ASP.NET MVC 2.0 lets you test drive your code, control the output of your HTML, and leverage C# and .NET in an easy-to-use web framework. This book shows you all you need to know to get started developing web applications using test-driven development (TDD). You'll learn how to do everything from creating your first test, to building REST web services, to deploying your finished ASP.NET MVC applications. Test-Drive ASP.NET MVC gets you started with all the fundamentals you need, whether you're transitioning from older Microsoft technologies, or if you're coming from an open-source background and are curious about what ASP.NET MVC has to offer. ASP.NET MVC 2.0 is C# on the web done right. No more fiddling around with Viewstate, IsPostBack(), and drag-and-drop coding. Microsoft has addressed the shortcomings of ASP.NET and created a framework that goes toe-to-toe with other popular web frameworks such as Ruby on Rails. Programming in C# is fun again! This book takes a test-first approach to the main features of ASP.NET MVC. You'll get hands-on experience building and deploying a time-management web application from start to finish. From building your first page, to data access, to integrating with web services such as Blogger.com, Test-Drive ASP.NET MVC guides you step by step. You'll come away with a complete understanding of web services and data access, and you'll learn how to test each component so that your code is bug-free and maintainable from the start. You'll see how to handle security, logging, and error handling. Software isn't useful until it's deployed into production. We'll cover automated deployment using MSBuild, a build tool product that can help you get your site online, repeatably and reliably. Throughout, you'll work with open source projects that complement ASP.NET MVC, including NHibernate, MVCContrib, and Castle Windsor Container. These tools speed up developing database components, architecture layers, and testing your code. As you build and deploy your application, you'll not only learn the framework itself, but also gain valuable experience with the test-first methodology, driving your application development through small and measurable incremental improvements. (edited by author)


Processing markup in object-oriented languages often requires the programmer to focus on the objects generating the markup rather than the more pertinent domain objects. The BetterXML framework aims to improve this situation by allowing the programmer to develop a domain-specific object model as usual and later bind this model to preexisting or newly generated markup. To this end, the framework provides two types of object trees, XElement and NaturalXML, for representing XML documents. XElement goes beyond DOM-like automatic parsing of XML by supporting the custom mapping of elements to domain objects; NaturalXML allows the mapping of existing domain objects to XML elements using class metadata. Both types of object trees can be inflated and deflated by means of a common intermediate representation in the form of an event stream. Finally, the framework includes the XML Intermediate Representation (XIR), a lossless record-oriented representation of XML documents for efficient streaming and other types of data exchange.


Every day the U.S. Department of Defense (DoD) uses 297,451 diapers; prepares 594,902 servings of "liquid baby rations"; issues purchase orders for cribs, strollers, and rocking chairs; and sings thousands of lullaby "cadences." (1) It was not always that way. The profile of the U.S. Armed Forces has changed from that of single members living in barracks, to one of a diverse volunteer workforce with growing numbers of female service members, working spouses, and sole and dual military parents. (2) Child care has become a workforce issue vital to U.S. Army, Navy, Air Force, and Marine families and to the military mission. The military child care program is truly a Cinderella story. At one time, it was known as the "ghetto of American child care" with unsafe and unsuitable facilities, weak standards that were sporadically enforced, staff who were poorly trained and compensated with turnover rates at some centers as high as 300%, and a general lack of oversight and attention from military officials. (3) In the past dozen years, however, military child care has achieved a remarkable turnaround. Today it is acclaimed as a model for the nation, (4-6) and described as the "gold standard for child care." (7) Fully 50% of the children in military child care programs are under age three, and this article describes the military's approach to providing flexible, high-quality, affordable infant and toddler child care. An Example of Employer-Sponsored Care Before launching the largest employer-sponsored child care program in the country, the military services looked primarily to the private sector to meet the child care needs of their personnel. Those needs are special, however. Military work schedules require early morning and irregular duty hours, field exercises, and extended periods away from home. Families move every few years and must reestablish routines and child care arrangements with every new assignment. Service members posted overseas face language problems, and often their host nations lack child care services. In some instances they are in hostile environments. Few can depend on care by relatives. Even in the United States, the hours offered by off-post, civilian child care programs are too limited to help military families counter the instability in their work lives and bridge the distance separating them from relatives. Infant and toddler child care is difficult to find and expensive, and programs seldom admit children under six months of age. M oreover, the quality of care varies greatly in the communities surrounding military bases because child care licensing standards differ from state to state. This variability leaves military families unsure of the child care conditions they will find as they move from post to post. In the wake of concerns over widely publicized child abuse scandals, congressional hearings culminated in the Military Child Care Act of 1989, which made far-reaching recommendations for improving the care provided by the military services. The DoD responded by creating a system of child care options, oversight to maintain standards and safety, training and improved wages for staff, accreditation to improve quality, and cost sharing to improve affordability. The comprehensive child care system that resulted now extends safe, high-quality care each day to more than 170,000 children from birth through age 12, at 300 locations around the world. (8) Developing a Seamless Child Care System The children in military families are served through a delivery system that includes child development centers, networks of family child care homes operated in government housing units and off base, and programs for school-age children. Many military bases also have outreach programs that provide on-site care during special functions, sponsor playgroups, and refer families to accredited child care programs in the civilian community. This delivery system is seamless, meaning there is a single point of entry to access care. …


Background: In recent years, laparoscopic sleeve gastrectomy (LSG) has become more acceptable for obese patients. Single-port sleeve gastrectomy (SPSG) is more popular since each abdominal incision carries the risk of bleeding, hernia, and internal organ injury as well as exponentially affecting cosmesis. This cross-sectional study aimed at comparing multi-port sleeve gastrectomy (MPSG) and SPSG in terms of their early results and complications. Methods: Out of129 obese patients candidated for LSG, 102 patients were assigned to 2 groups of SPSG and MPSG. Complications and demographic data such as body mass index (BMI), age, gender, operation time, and hospital stay were measured. All surgeries were carried out between2013 and 2015 in Shiraz, Iran. Data analysis was performed using SPSS, version 16 for Windows (SPSS Inc., Chicago, IL). The continuous and categorical variables were compared using the Student t-test and the Chi-square test or the Fisher exact test, respectively. Results: The patients' data from both groups were similar in terms of age, intraoperative and postoperative bleeding volume, and length of hospital stay. Mean BMI was 42.8±0.7 in the SPSG group and 45.3±1.2 in the MPSG group. Duration of surgery was significantly lower in the SPSG group (P<0.001). Only 1 patient from the SPSG group and 5 patients from the MPSG group had bleeding as an early complication. Conclusion: The differences in each complication between the groups were not statistically significant. SPSG seems to be safe and is the same as MPSG in terms of major postoperative complications. Trial Registration Number: IRCT201512229936N12 The abstract was presented in the 4th International Congress of Minimally Invasive Surgery, Iran, as a poster and published in Iran J Med Sci Journal as a supplement (May 2015; Vol. 40, No. 3).


Mediation promises a way for conflicting parties to address differences and reach an agreement to settle their dispute. This study looks at mediation discourse of five cases from a university conflict resolution center through the lens of Girard's (1977) theory of mimetic desire. Girard (1977) suggests that we are all in a pattern of mimesis. Antagonism that is prevalent in conflict develops, in Girard's view, from the cycle of desire when one person wants an object and another person copies that desire for the object. The two parties quickly forget the object, but antagonism emerges as the mimetic desire continues. Girard argues parties have a tendency to place blame on a scapegoat to break the antagonism pattern. Alternatively, in her application of Girard's theory, Cobb (1997, 2003, 2010a, 2010b) advocates a social constructionist perspective where disputants work on turning thin conflict stories into thicker ones to break the pattern.
This project addresses a need for research on cycles of antagonism in discourse constructed by disputants during real mediation sessions. Knowing how disputants construct discourse lends insight into how people handle their most challenging interpersonal problems. The analysis of discourse through the guiding frameworks of conflict tactics, production format, and tenor of discourse sheds light on how disputants construct perpetuated mimicked antagonism and how they break the pattern. Additionally, findings highlight the emergence of weapons and wounds in the discourse suggesting that communicative violence is constructed whether or not there was actual physical violence.
Components of thin conflict narratives are evident in findings from all five cases. Yet, while two cases are characterized by discourse of perpetuated mimicked antagonism, three represent a break in that pattern without placing blame on a scapegoat or constructing a thicker conflict narrative. The distinctions between a perpetuated and broken cycle are unpacked through the discussion of: a) animator-only position; b) indirectness and presumptive attribution; and c) shift in footing between talking to the other disputant and the mediators. This project provides a more nuanced understanding of the Girardian perspective relating to conflict mediation to contribute to the extant literature on conflict discourse and mediation practice.


In most sentiment analysis applications, the sentiment lexicon plays a key role. However, it is hard, if not impossible, to collect and maintain a universal sentiment lexicon for all application domains because different words may be used in different domains. The main existing technique extracts such sentiment words from a large domain corpus based on different conjunctions and the idea of sentiment coherency in a sentence. In this paper, we propose a novel propagation approach that exploits the relations between sentiment words and topics or product features that the sentiment words modify, and also sentiment words and product features themselves to extract new sentiment words. As the method propagates information through both sentiment words and features, we call it double propagation. The extraction rules are designed based on relations described in dependency trees. A new method is also proposed to assign polarities to newly discovered sentiment words in a domain. Experimental results show that our approach is able to extract a large number of new sentiment words. The polarity assignment method is also effective.


In December 1920, on the eve of the introduction of the New Economic Policy (NEP), the Bolsheviks embarked on a crash campaign to avert an agricultural crisis. The Eighth Congress of Soviets passed legislation known by the name of one of its principal innovations, the sowing committees (posevkomy). The usual view of this legislation is that it was a last binge of revolutionary inebriation before the sobering morning after of NEP -a desperate attempt to use civil-war methods to undo the damage done by civil-war methods. The full record of the legislation and the debate surrounding it tell a different story.


Following an inversion ankle joint sprain, damage to the proprioceptive organs can occur, which is made worse by lack of proprioceptive retraining and will increase the chances of re-injury (Hoffman and Payne 1995:144 and Anderson, 2002). Pellow and Brantingham (2001) indicated that patients who received multiple manipulations improved more rapidly than patients in the placebo group. Therefore it is proposed that manipulation provokes changes in afferent input that may restore normal proprioceptive input (Slosberg, 1988). However, Pellow and Brantingham (2001) were not able to establish what effect multiple manipulations had, as opposed to a single manipulation, on the proprioception on the foot and ankle complex and how this may influence the clinical outcome of the patient's treatment. Therefore, it was hypothesized that multiple manipulations of the foot and ankle complex would have a greater effect on chronic ankle instability syndrome than a single treatment in terms of overall improvement subjectively and objectively. In addition to this the following was also hypothesized: • That multiple manipulations of the foot and ankle complex would increase the ROM to a greater extent than single manipulations. • That multiple manipulations would decrease point tenderness more effectively than a single manipulation.


The concept of risk management is present in quality assurance of higher education institutions in different scope and scale, seeking the rationality of its use in effectiveness and innovation in internal quality assurance systems. The paper argues that the risk management in internal quality assurance could be introduced in different ways, including: top down and bottom up approaches. Based on the case study from Warsaw University of Life Sciences-SGGW it also explains how risk management could be implemented as the innovative tool.


Examining a range of sixth-century (A.D.) literary sources, this paper explores the authors9 attitudes toward the marital relationship of the Late Roman emperor Justinian I and his empress, Theodora. It emerges that the sources characteristically appeal to the agency of Theodora or to an underlying level of mutual understanding between the imperial couple in order to reconcile inconsistencies or apparent contradictions between the regime9s rhetoric and its actions. Recourse to such an interior dynamic gave scope to the recognition and expression of contradiction without thereby entailing an admission of disorder: it enabled the imperial couple, and thus in an overarching sense the instrumental function of the imperial "role" in the state, to work if necessary at cross purposes while preserving an unbroken unity of purpose. Special attention is paid to the particular interests and expectations of two distinct groups: the classically-educated mandarinate of the Roman civil service, and the schismatic hierarchy of the nascent Monophysite church.


We develop a coupled model of regional migration and lake ecology to study the influence of ecological-economic interactions and relative time scales on transient and asymptotic dynamics. Cross-scale interactions fundamentally change system dynamics by eliminating steady states that are present in the decoupled economic model and introduce important time dependence. We find that the relative time scales of interacting variables are a key determinant in system dynamics and resilience and that the system's asymptotic behavior cannot be determined without considering the full dynamics of the system. Other time-dependent effects are found to matter, e.g., when households base their perceptions of environmental amenities on past observation, a path dependence is introduced that can lead to oscillations or decline in transient population. Finally, interactions are found to multiply the costs and benefits of policy by inducing a positive feedback between the ecological and economic components that can reinforce or offset the direct effect of the policy. Such effects imply that the economic and ecological costs of getting the policy wrong can be large. Our findings underscore the critical importance of accounting for multiple time scales and time dependence and suggest that models that ignore such complications can be quite misleading. At best, such models will fail to capture the full dynamics of the system and at worst, could provide a misleading characterization of the basic dynamical structure of these systems.


The experimental observation of a one-dimensional evanescent wave supported by a 90◦ metal edge is reported. Through a measurement of in-plane momenta, we clearly demonstrate the dimensional character of this surface wave and show that it is non-radiative in the superstrate. Excitation conditions, lateral extension and polarization properties of this wave are discussed. Finally, we explore the effect of the surrounding dielectric medium and demonstrate that a single edge can sustain distinct excitations.


A human science in inhuman times : Dreyer Kruger and phenomenological psychology in South Africa, 1976-90This article discusses the development of phenomenological psychology in South Africa from the mid-1970s to 1990, with specific reference to the pioneering work done by Dreyer Kruger and his contemporaries at Rhodes University. It focuses specifically on the limitations of this approach as a critical psychology during this period - that is, as a psychology that could meaningfully engage the distortion of human subjectivity, experience and relationships brought on by apartheid and racial-capitalist policies, practices and structures. The point of departure is Kruger's formulation of phenomenological psychology as not just an epistemological critique of positivism, but also a form of societal and political critique. It is argued that the eventual discrepancy between Kruger's critical vision and what passed in practice as phenomenological psychology by him and his contemporaries cannot simply be attributed to their inability to express Kruger's critical vision in practice. The failure of phenomenological psychology to shape a critical psychology reveals limitations that are inherent to phenomenological psychology. Through a reading based on Bourdieu's concepts of habitus, field and distinction, phenomenological psychology is presented here as having been overly committed to an epistemology that treated knowledge production as a detached, neutral and transparent practice, consequently upholding a particular class habitus, that of a middle-class, white South African reality, as normative.


The production of recombinant proteins is a problem of significant interest in bioengineering. Because of the existing trade-off between cellular growth and protein production, these two processes are separated in time in most commonly-employed strategies: a growth phase is followed by a production phase. Here, we investigate the potential of an alternative strategy using artificial cell specialization and differentiation systems in which cells either grow ("growers") or produce proteins ("producers") and growers can irreversibly "differentiate" into producers. Inspired by an existing two-population system implemented in yeast, we propose a model of a "yeast synthetic stem cell system" and define an optimal control problem to maximize bioproduction. Analytically, we first establish the well-posedness of the problem. Then, we prove the existence of an optimal control and derive non trivial optimality conditions. We finally use these results to find numerical optimal solutions. We conclude by a discussion of extensions of this work to models that capture the heterogeneity of the cell response to differentiation signals.


Approximately 14 percent of births are unregistered in Latin America according to estimates by UNICEF (2001). Children who lack an official birth certificate can be denied access to social services, including enrolling in school and accessing health services. This paper examines the under-registration of births in six Latin American countries (Bolivia, Brazil, Colombia, the Dominican Republic, Peru, and Nicaragua) using Demographic and Health Surveys (DHS). Under-registration of children younger than 5 is found to range from 8. 4 percent in Peru to 25. 8 percent in the Dominican Republic. Striking regional differences are found in all six countries.


OBJECTIVE
To describe problems noted during central venous jugular catheter (CVJC) placement, conditions associated with unsuccessful catheterization, and CVJC maintenance complications.

DESIGN
Prospective observational study from September 2014 to September 2015.

SETTING
University veterinary teaching hospital.

ANIMALS
Twenty-seven dogs and 20 cats hospitalized in a veterinary ICU. Patients were excluded if previously hospitalized with a CVJC or lacked sufficient data.

INTERVENTIONS
None.

MEASUREMENTS AND MAIN RESULTS
Ninety-one percent of indwelling CVJCs were placed successfully (43/47, 95% CI: 80%, 98%). Procedural-related difficulties that resulted in the inability to place a CVJC totaled 18/63 (28.6%, 95% CI: 18%, 41%) and included the inability to puncture the vessel (10), hematoma (6), malposition (1), and dislodgement (1). Procedural complications occurred in 24/47 patients (51%, 95% CI: 36%, 66%) and included cardiac dysrhythmias (13), hematoma (6), CVJC placement failure (4), and malposition (1). Risk factors associated with multiple catheterization attempts included increased age (7.5 years [± 4.2] vs 10.6 years [± 4.1], P = 0.04), smaller size (8.0 kg [0.6-51.9 kg] vs 4.4 kg [2.6-6.8 kg], P < 0.01) and thinner body condition score (median 5/9 [2/9-9/9] vs 4/9 [2/9-7/9], P = 0.04). The risk factor associated with dysrhythmias was smaller patient size (6.8 kg [2.6-51.9 kg] vs 4.8 kg [0.6-29.5 kg], P = 0.04). Eighteen indwelling complications occurred in 14 patients and included mechanical obstruction (7), skin irritation (6), malposition (4), and inflammation (1). Risk factors for indwelling complications included longer dwell time (5 days [2-30] vs 3 days [1-10], P < 0.01) and the administration of an irritant medication (P = 0.02).

CONCLUSIONS
Complications were documented in the placement and maintenance of CVJCs in critically ill patients with a low incidence of life-threatening sequelae. Risk factors associated with both unsuccessful CVJC placement and indwelling CVJC complications were identified.


InSiDDe (In Silico Disorder Design) is a program for the in silico design of intrinsically disordered proteins of desired length and disorder probability. The latter is assessed using IUPred and spans values ranging from 0.55 to 0.95 with 0.05 increments. One to ten artificial sequences per query, each made of 50 to 200 residues, can be generated by InSiDDe. We describe the rationale used to set up InSiDDe and show that an artificial sequence of 100 residues with an IUPred score of 0.6 designed by InSiDDe could be recombinantly expressed in E. coli at high levels without degradation when fused to a natural molecular recognition element (MoRE). In addition, the artificial fusion protein exhibited the expected behavior in terms of binding modulation of the specific partner recognized by the MoRE. To the best of our knowledge, InSiDDe is the first publicly available software for the design of intrinsically disordered protein (IDP) sequences. InSiDDE is publicly available online.


The pattern of global gene expression in Salmonella enterica serovar Typhimurium bacteria harvested from the chicken intestinal lumen (cecum) was compared with that of a late-log-phase LB broth culture using a whole-genome microarray. Levels of transcription, translation, and cell division in vivo were lower than those in vitro . S. Typhimurium appeared to be using carbon sources, such as propionate, 1,2-propanediol, and ethanolamine, in addition to melibiose and ascorbate, the latter possibly transformed to D -xylulose. Amino acid starvation appeared to be a factor during colonization. Bacteria in the lumen were non- or weakly motile and nonchemotactic but showed upregulation of a number of fimbrial and Salmonella pathogenicity island 3 (SPI-3) and 5 genes, suggesting a close physical association with the host during colonization. S. Typhimurium bacteria harvested from the cecal mucosa showed an expression profile similar to that of bacteria from the intestinal lumen, except that levels of transcription, translation, and cell division were higher and glucose may also have been used as a carbon source.


The development of American family law, particularly the enumeration of rights, has often paralleled that of personal rights generally. All the same, neither the federal Bill of Rights nor counterpart state provisions offer explicit familial guarantees comparable to those traditionally conferred upon individuals. What prevails is a presumption that the family unit ought not to be subjected to intrusive control or supervision. There have even been reports of a proposed federal constitutional "amendment prohibiting the government from abridging the 'rights of the family.'" (1) Over the years, a sense of privacy seems to have precluded societal intervention unless egregious conditions necessitated it. The onus of responsibility lies with the state in establishing compelling reasons for any attempt to remedy misdeeds. Throughout the nation's history, the recurring motif has favored non-interference, suggesting a conception of family law that belies overt paternalism. In this regard, procedural and substantive rights have accrued to the family, viewed as an entity essential not only to the individuals who comprise it, but also to the preservation of accepted social needs and goals. The essay that follows does not focus upon issues and questions encompassed within the customary bounds of family law. (2) Instead, emphasis has been placed upon a review of contemporary cases that have touched upon unusual themes affecting internal relationships and conflicts both within and outside the family unit. Additionally, in the major cases, constitutional aspects (or their absence) are treated either directly or impliedly. Attention is directed to controversies litigated in the state courts from which, historically, most of American family law originated and where it continues to be centered. The cases often reflect a revived judicial federalism and are marked by nuances in an ever-growing and changing body of law. THE FEDERAL JUDICIAL FRAMEWORK The first glimpses of legal recognition for family autonomy arose within settings not integrally related to familial relations. Among the earliest cases suggesting a protective framework was Meyer v. Nebraska, (3) initiating occasional spurts of judicial inquiry. The sanctity and integrity of the family unit had long been recognized but without reference to specific constitutional language or, until Meyer, even to the common law. It was from the latter that a listing of individual rights and privileges, including the "right to marry, establish a home and bring up children," was derived as "essential to the orderly pursuit of happiness by free men." (4) When the Supreme Court acknowledged the existence of these rights in 1923, they were linked to conceptions of liberty, though it is noteworthy that they were not defined with exactness. (5) Almost simultaneously, the Court in Pierce v. Society of Sisters went on to sustain the "liberty of parents and guardians to direct the upbringing and education of children under their control." (6) Overtones of now much-decried substantive due process pervaded both opinions. In Meyer, the Court referred to the Fourteenth Amendment's due process clause as preventing the states from interfering with individual contractual rights, (7) thus raising the specter of a continued reliance on Lochner v. New York, (8) subsequently taken to be among the most denounced precedents of the century. The opinions in Meyer and Pierce were written by Justice James McReynolds, (9) one of the most conservative members of the Court. In both cases, questions were raised concerning the types of schools that children should be required to attend and the foreign languages that they might elect to study. The former centered on state efforts to discourage attendance at parochial schools. (10) The latter, in large measure a legacy of World War I, was designed to eliminate the study of the German language as a part of the curriculum. (11) Whether in a broader, more inclusive context, family rights would have been set out with greater attention to scope and breadth remained problematic at the time. …


An important Late Middle Cambrian fossil locality occurs 2 km west of St.
Valentines Peak in north-western Tasmania. The Cambrian rocks to the north and west
of St. Valentines Peak are exposed in the core of the north-south trending St.
Valentines Peak Anticline. In the best exposed section (3 km north of the main fossil
locality), the oldest Cambrian unit is a massive, cherty, pyritic meta-sandstone and
meta-siltstone at least 100 m thick. This is overlain by 100 m of rhyolitic welded
tuff, 75 to 100 m of meta-sandstones and meta-siltstones, 100 m of a possible contact
metasomatic rock and 230 to 375 m of a pale grey chert which in turn is overlain by
about 17 m of fine breccia and poorly fossiliferous siltstone. This sequence is overlain
with probable disconformity by the basal chert conglomerate of the essentially
Ordovician Junee Group. It is suggested that the sediments of the main fossiliferous
locality occur stratigraphically below the section noted above. The Cambrian and
Ordovician rocks are intruded by Devonian granite and partly overlain by Tertiary
basalt.


The current design practice used by WSDOT for the design of permanent tieback walls is to assume that the static design of a tieback wall retaining clayey soils provides an adequate reserve of strength to prevent failure during seismic loading. This design procedure is based largely on the assumption that the soil and the wall move together during ground shaking and that significant dynamic loads are not produced. For tieback walls retaining sandy soils, it is assumed that dynamic loads are produced. Mononobe-Okabe dynamic soil pressures are added to the static design pressure to account for the dynamic load. The validity of these assumptions and the resultant design practices is evaluated in this study. A pilot numerical study was conducted on a forty foot high wall with three levels of tiebacks using the program FLUSH. It was found that the wall and the soil tend to move in-phase and only negligible dynamic tie forces are generated. However, the soil above and below the excavation level tends to move out-of-phase, leading to significant dynamic pressures and bending moments in the wall and near the excavation level. It appears that in some cases, tieback walls with an adequate static safety factor may suffer significant damage or fail during seismic loading and that the use of Mononobe-Okabe dynamic prssures may be conservative.


Adding the angiogenesis inhibitor bevacizumab to initial
standard chemotherapy followed by bevacizumab alone as
maintenance therapy prolongs progression-free survival
(PFS) time significantly but modestly in women with
advanced epithelial ovarian cancer. This finding has been
reported consistently by two phase III trials, GOG-218
and ICON 7. At present, overall survival (OS) data are
immature. Therefore, no recommendation can be made
yet how to best incorporate bevacizumab in the front-line
treatment of advanced ovarian cancer.
Members of the gynecological cancer working group of
the Swiss Group for Clinical Cancer Research (SAKK) and
other specialists have discussed the latest findings with
bevacizumab in ovarian cancer and their consequences for
clinical practice.
Ovarian cancer is the seventh most frequent cancer in
women worldwide (1). Its incidence rates are highest in
the western world, where it is the leading cause of death
from gynecological malignancies (2, 3).
Patients with stage III and IV ovarian cancer require a
combined approach of surgery and chemotherapy. Primary
debulking surgery plays a key role and the final outcome
is highly dependent on the results achieved with the initial
surgery: a residual tumor of >1 cm was found to be associated
with a median overall survival of 12–16 months,
while a longer median overall survival has been reported
in patients with no macroscopic residual disease (4). The
ultimate goal of surgery is cytoreduction to microscopic
disease, the term optimal cytoreduction being reserved for
those cases with no macroscopic residual disease.
The standard first-line chemotherapy for advanced ovarian
cancer usually contains a taxane and a platinum agent
for six cycles (5-8). The response rate for this treatment is approximately 75%. However, 65% of these patients will
develop tumor progression in the first three years after diagnosis.
Over the past ten years, the only improvement in
overall survival has been reported with the introduction of
a dose dense schedule of paclitaxel (9) or by the use of local
ip treatment in selected patients (10); the addition of a
third cytotoxic to standard chemotherapy has not showed
any significant advantage over the established first-line
chemotherapy (11, 12).


A new paradigm has emerged recently in financial modeling: rough (stochastic) volatility. First observed by Gatheral et al. in high‐frequency data, subsequently derived within market microstructure models, rough volatility captures parsimoniously key‐stylized facts of the entire implied volatility surface, including extreme skews (as observed earlier by Alòs et al.) that were thought to be outside the scope of stochastic volatility models. On the mathematical side, Markovianity and, partially, semimartingality are lost. In this paper, we show that Hairer's regularity structures, a major extension of rough path theory, which caused a revolution in the field of stochastic partial differential equations, also provide a new and powerful tool to analyze rough volatility models.


The addition of both full and partial muscarinic agonists to human SK-N-SH neuroblastoma cells resulted in a sustained phosphoinositide (PPI) hydrolysis for up to 2 hr, as monitored either by the accumulation of [3H]inositol phosphates (IP) in the presence of Li+, or alternatively, by an increased labeling of phosphatidate and phosphatidylinositol (PI) from 32Pi. This enhanced PPI hydrolysis was maintained even though 40-50% of cell-surface muscarinic cholinergic receptors (mAChRs) became sequestered. Desensitization of carbachol-stimulated PPI hydrolysis was only detected after a 2-4 hr prior exposure of the cells to the agonist and was accompanied by a comparable reduction in total mAChR number. Prolonged incubation of SK-N-SH cells with the partial agonist bethanechol also resulted in a desensitization of stimulated PPI turnover but at a slower rate than that observed for carbachol and with a loss of fewer mAChR sites. Desensitization of mAChR-stimulated [3H]IP formation appeared to occur more rapidly in mouse NIE-115 neuroblastoma. However, Li+ could not fully prevent the degradation of accumulated [3H]IP in these cells. When an increase in [32P]phosphatidylinositol labeling was used to assess PPI turnover in NIE-115 cells, no desensitization was evident for up to 2 hr. We conclude that 1) in SK-N-SH cells, desensitization more closely parallels the down-regulation than the sequestration of mAChRs, 2) in both neuroblastomas, stimulated PPI hydrolysis desensitizes relatively slowly and 3) the appearance of desensitization can vary as a function of the assay method employed.


ABSTRACT Constitutive NOTCH signaling in lymphoid progenitors promotes the development of immature T-cell lymphoblastic neoplasms (T-ALLs). Although it is clear that Notch signaling can initiate leukemogenesis, it has not previously been established whether continued NOTCH signaling is required to maintain T-ALL growth. We demonstrate here that the blockade of Notch signaling at two independent steps suppresses the growth and survival of NOTCH1-transformed T-ALL cells. First, inhibitors of presenilin specifically induce growth suppression and apoptosis of a murine T-ALL cell line that requires presenilin-dependent proteolysis of the Notch receptor in order for its intracellular domain to translocate to the nucleus. Second, a 62-amino-acid peptide derived from a NOTCH coactivator, Mastermind-like-1 (MAML1), forms a transcriptionally inert nuclear complex with NOTCH1 and CSL and specifically inhibits the growth of both murine and human NOTCH1-transformed T-ALLs. These studies show that continued growth and survival of NOTCH1-transformed lymphoid cell lines require nuclear access and transcriptional coactivator recruitment by NOTCH1 and identify at least two steps in the Notch signaling pathway as potential targets for chemotherapeutic intervention.