This study aims to find out: 1) What is the type of parenting in Class B children in ABA Kindergarten Sidoharjo, 2) What is the level of cognitive development in Class B children in ABA Kindergarten Sidoharjo, 3) How is the relationship between parenting and cognitive development in children in kindergarten ABA Sidoharjo especially class B. This type of research is a quantitative quantitative study with a population of class B, ABA Sidoharjo kindergarten, which is 28 children. Data collection uses questionnaires, observation sheets and documentation. Analysis of data using chi square and product moment techniques with the help of SPSS version 18. computer program. The results showed that the type of parenting parents applied to ABA Sidoharjo Kindergarten class B students were 53.6% authoritarian parenting, democratic parenting 39.3% and permissive parenting 7.1%. The level of cognitive development of class B children in ABA Sidoharjo kindergarten includes good cognitive development with a percentage of 14.3%, fairly good cognitive development of 71.4% and unfavorable cognitive development of 14.3%. Then there is a positive relationship between parenting and cognitive development of children, as evidenced by the results of chi square with Asymp. Sig. equal to 0.030 whose probability number is below 0.05. Furthermore, from the three parenting styles that have a positive relationship with cognitive development is the upbringing of democracy as evidenced by the results of r = 0, 744 n p = 0,000. It can be concluded that there is a relationship between parenting parents with cognitive development of children or children with parenting parents, especially parenting democracy will provide good cognitive development, while children with authoritarian parenting will provide adequate or less good cognitive development, so too children with permissive parenting.


Manufacturers are invited to send details of new products to be included in this section. All information supplied should be strictly factual. The text may be altered by the editors. There is no charge to the manufacturers of products featured in this section and the journal accepts no responsibility for the accuracy of the information provided. Please send details to Dr J Fenner, Associate Editor (JMET), Medical Physics (Dept. Infection, Immunity and Cardiovascular Disease), Faculty of Medicine Dentistry and Health, University of Sheffield, Beech Hill Road, Sheffield, S10 2RX, UK. E-mail: email@example.com. Disclosure statement: The News and Product Update is compiled and edited by Dr J Fenner. The author reports no conflict of interest with the contents, products or manufacturers featured in the News and Product Update, unless stated otherwise.


Background Analysing tumour architecture for metastatic potential usually focuses on phenotypic differences due to cellular morphology or specific genetic mutations, but often ignore the cell's position within the heterogeneous substructure. Similar disregard for local neighborhood structure is common in mathematical models. Methods We view the dynamics of disease progression as an evolutionary game between cellular phenotypes. A typical assumption in this modeling paradigm is that the probability of a given phenotypic strategy interacting with another depends exclusively on the abundance of those strategies without regard local heterogeneities. We address this limitation by using the Ohtsuki-Nowak transform to introduce spatial structure to the go vs. grow game. Results We show that spatial structure can promote the invasive (go) strategy. By considering the change in neighbourhood size at a static boundary – such as a blood-vessel, organ capsule, or basement membrane – we show an edge effect that allows a tumour without invasive phenotypes in the bulk to have a polyclonal boundary with invasive cells. We present an example of this promotion of invasive (EMT positive) cells in a metastatic colony of prostate adenocarcinoma in bone marrow. Interpretation Pathologic analyses that do not distinguish between cells in the bulk and cells at a static edge of a tumour can underestimate the number of invasive cells. We expect our approach to extend to other evolutionary game models where interaction neighborhoods change at fixed system boundaries.


The adjoint method is used to calibrate the medium complexity climate model "Planet Simulator" through parameter estimation. Identical twin experiments demonstrate that this method can retrieve default values of the control parameters when using a long assimilation window of the order of 2 months. Chaos synchronization through nudging, required to overcome limits in the temporal assimilation window in the adjoint method, is employed successfully to reach this assimilation window length. When assimilating ERA‐Interim reanalysis data, the observations of air temperature and the radiative fluxes are the most important data for adjusting the control parameters. The global mean net longwave fluxes at the surface and at the top of the atmosphere are significantly improved by tuning two model parameters controlling the absorption of clouds and water vapor. The global mean net shortwave radiation at the surface is improved by optimizing three model parameters controlling cloud optical properties. The optimized parameters improve the free model (without nudging terms) simulation in a way similar to that in the assimilation experiments. Results suggest a promising way for tuning uncertain parameters in nonlinear coupled climate models.


This paper analyzes the impact of liquid asset holdings on bank profitability for a sample of Iranian banks. Using the Generalized Method of Moment (GMM), this study analyzes the profitability of listed banks using unbalanced panel data over the period of 2002-2009. We use the liquidity asset and liquidity asset-ratio square for estimating liquid asset and profitability relationship. The estimated relationship between liquid assets and bank profitability is as expected. Coefficients for the liquid assets ratio, its square, business cycle, regulation and its product are all statistically significant. As expected, we found evidence of a non-linear relationship between profitability and liquid asset holdings. An important finding of this study is that the business cycle significantly affects bank profits. The coefficient of business cycle has a positive and statistically significant impact on bank profitability in results of the model this suggests that profitability exhibits pro-cyclical behavior. The coefficient of regulation is negative and significant. Therefore, if regulators reduce the constraints imposed on banks, banks can make profits.


The Iraq and Afghanistan conflicts, taken together, will be the most expensive wars in US history--totaling somewhere between $4 to $6 trillion. This includes long-term medical care and disability compensation for service members, veterans and families, military replenishment and social and economic costs. The largest portion of that bill is yet to be paid. Since 2001, the US has expanded the quality, quantity, availability and eligibility of benefits for military personnel and veterans. This has led to unprecedented growth in the Department of Veterans Affairs and the Department of Defense budgets. These benefits will increase further over the next 40 years. Additional funds are committed to replacing large quantities of basic equipment used in the wars and to support ongoing diplomatic presence and military assistance in the Iraq and Afghanistan region. The large sums borrowed to finance operations in Iraq and Afghanistan will also impose substantial long-term debt servicing costs. As a consequence of these wartime spending choices, the United States will face constraints in funding investments in personnel and diplomacy, research and development and new military initiatives. The legacy of decisions taken during the Iraq and Afghanistan wars will dominate future federal budgets for decades to come.


We conducted a statistical analysis to characterize the influence of large-scale and local environmental factors on presence-absence, concentration, and assemblage structure of larval fish within the northern California Current (NCC) ecosystem, based on samples collected at two nearshore stations along the Newport Hydrographic line off the central Oregon coast. Data from 1996 to 2005 were compared with historical data from the 1970s and 1980s to evaluate pseudo-decadal, annual, and seasonal variability. Our results indicate that the most abundant taxa from 1996 to 2005 differ from those of earlier decades. Concentrations of the dominant taxa and total larvae were generally greater in the winter/spring than summer/fall season. Using generalized additive modeling, variations in presence-absence and concentration of taxa were compared to climate indices such as the Pacific Decadal Oscillation, Northern Oscillation Index, and the multivariate ENSO index and local environmental factors, such as upwelling, Ekman transport, and wind stress curl. Significant relationships were found for various combinations of environmental variables with lag periods ranging from 0 to 7 months. We found that the large-scale climate indices explained more of the variance in larval fish concentration and diversity than did the more local factors. Our results indicate that readily available oceanographic and climate indices can explain variations in the dominant ichthyoplankton taxa in the NCC. However, variation in response among taxa to the environmental metrics suggests additional unknown factors not included in the analysis likely contributed to the observed distribution patterns and larval fish community structure in the NCC.


This Guidance was developed by the Ministry of Labour to assist the workplace parties on matters relating to the establishment, operation and maintenance of Multi-workplace Joint Health and Safety Committees.


Gold crescent-shaped nanoparticles, exhibiting multiple resonances in the visible and near-infrared spectral region, were characterized in terms of their optical response to thin dielectric coatings. A strong red shift of the resonances is observed upon the addition of material. The coating thickness at which saturation of the shift sets in is resonance dependent and is directly connected to the spatial extension of the near field associated to each of the plasmonic modes, which is estimated through simplified theoretical models. These structures are advantageous for sensing for two reasons. First, the small modal volume makes them selectively sensitive to the first 10-30 nm distance from the gold. Second, each mode yields independent information about the coating and therefore in principle allows the determination of more than one free parameter of the coating, for example, thickness and refractive index.


Commentators differ on whether nuclear disarmament would be desirable, but many argue that disarmament is impractical because it could not be verified. Three reasons are often offered for such pessimism. First, nuclear weapons are small and difficult to detect, and one could not be sure that a few weapons had not been hidden away. Second, nuclear weapons are so destructive that a mere handful would confer enormous military and political advantages over non-nuclear adversaries. Finally, nuclear know-how cannot be eliminated, and any nation that had dismantled its nuclear weapons would be capable of quickly assembling a new arsenal from scratch or using civilian nuclear materials. Because of the difficulty of verifying that other states had eliminated all their weapons and providing adequate warning of their rearming, it is argued, states would not agree to disarm in the first place.


Lothagam, located west of Lake Turkana in northern Kenya, is an uplifted fault block comprising a gently westward-dipping sequence of volcanic and sedimentary rocks. The lower part of the sequence, lavas and coarse volcaniclastic sediments of the Nabwal Arangan beds, was deposited mainly between 14 Ma and 12 Ma (Mid-Miocene), although the uppermost basalt has a K-Ar age of 9.1 Ma. The overlying fluvial sediments of the lower Nawata Formation have yielded ages on five tuffaceous horizons ranging from 7.4 ±0.1 to 6.5 ±0.1 Ma, Late Miocene. A tuffaceous horizon in the overlying Apak Member of the Nachukui Formation, yields an age of 4.22 ± 0.03 Ma; 40Ar-39Ar age spectra on the succeeding Lothagam Basalt indicate an age of 4.20 ± 0.03 Ma for its eruption. Much of the rich faunal assemblage from the Nawata Formation derives from the tightly dated lower intervals. Two hominoid teeth from higher in the formation can only be constrained to lie between 6.5 and 5 Ma old. The hominoid mandible, KNM-LT 329, from the lower Apak Member is older than 4.2 Ma and younger than 5.0 Ma.


Recent advancements in fuel cells, known for their high efficiency in converting chemical energy into electrical energy with zero greenhouse gas emissions, prompts the need for efficient methods of hydrogen production, as most fuel cell systems require pure hydrogen as the fuel. Reforming of methanol and ethanol is one attractive route since, at least in theory, this pathway can be considered carbon neutral. This, in return, has motivated a study focusing on the development of highly active and selective catalysts for the steam reforming of alcohols. In this thesis, we discuss fundamental studies on two different steam reforming catalysts Cobased catalysts for steam reforming of ethanol (SRE) and PtZn bimetallic catalysts for steam reforming of methanol (SRM). Within the scope of Co-based catalysts, we have investigated the structure and reactivity of model catalysts consisting of Co films and particles supported on various metal oxides, such as ZnO(0001), YSZ(100), and CeO2/YSZ(100), to elucidate the mechanism of the SRE reaction on cobalt catalysts and identify the support effects. The results obtained demonstrate that partially oxidized cobalt is active for the partial oxidation of adsorbed ethoxide groups to produce acetaldehyde, which is thought to be a key intermediate in the SRE reaction. Comparison of the results obtained for the reducible (ZnO and CeO2) and non-reducible (ZrO2) supports shows that the facile transfer of oxygen from reducible supports may play a role in maintaining the cobalt in a partially oxidized state, and removing the deposited carbon on Co that is formed via unselective decomposition of ethanol. On the PtZn catalysts for SRM application, we have carried out a surface science study utilizing model catalysts of vapor deposited Zn on a Pt(111) single crystal to characterize the structural effect of incorporating Zn into Pt surfaces and its correlation towards methanol reactivity. It was discovered that the addition of Zn results in the stabilization of chemisorbed methanol allowing it to undergo an OH bond scission to form methoxy on the catalyst surface. These methoxy groups that are bound on Zn sites are found to undergo dehydrogenation to form formaldehyde, which is stable up to 400 K. Therefore, it is proposed that Zn effects are not limited only in electronically altering the properties of Pt, but also providing sites where the aldehyde intermediates are bound preventing them from undergoing further dehydrogenation to CO. Degree Type Dissertation Degree Name Doctor of Philosophy (PhD) Graduate Group Chemical and Biomolecular Engineering First Advisor John M. Vohs


The relationship between conflict and education has been studied before. However, previous authors have always focused strongly on the supply-side effects, whereas this article examines the influence of conflict on the demand for education. It is theoretically shown that, under relatively general conditions, individuals living in a conflict area have an incentive to increase their level of education and that this effect depends on the individual's skill level. This hypothesis is tested using the conflict in the Basque Region as a case study, which is an example of a conflict in which one would not expect strong supply-side effects. Using other Spanish regions, an artificial region is created in which the population has a similar educational distribution as in the Basque Region. When comparing the true and artificial regions, individuals with a medium education level clearly show an increase in education during the conflict, as predicted by the theoretical model.


The objective of this paper was to investigate the local distribution, abundance and population structure of Pagellus erythrinus, Pagellus bogaraveo and Pagellus acarne on the continental shelf and slope over a wide geographic area from Gibraltar to the Aegean Sea. The analysis was based on the data collected during six trawl surveys, from 1994 to 1999, carried out yearly in spring within the MEDITS EU project. P. acarne was mainly distributed on the continental shelf, with a relatively higher abundance in the western part of the Mediterranean basin, where the biomass indices of P. bogaraveo were also important on the continental slope. Throughout the studied area, P. erythrinus was mainly distributed on the continental shelf, with remarkable abundance indices in the eastern part of the Mediterranean and in Corsica´s waters. Mean total lengths showed a highly significant decreasing trend from the western to the eastern geographical sectors.


You might find this additional info useful...This article cites€44 articles, 28 of which you can access for free at: http://ajpheart.physiology.org/content/283/1/H5.full#ref-list-1This article has been cited by€12 other HighWire-hosted articles: http://ajpheart.physiology.org/content/283/1/H5#cited-by Updated information and services including high resolution figures, can be found at: http://ajpheart.physiology.org/content/283/1/H5.fullPhysiology can be found at: Additional material and information about American Journal of Physiology - Heart and Circulatoryhttp://www.the-aps.org/publications/ajpheartThis information is current as of July 24, 2013.


The purpose of this paper is to know the rules and regulations of sustainability reporting in Bangladesh, the extent of sustainability reporting practice, way of reporting in banking companies of Bangladesh and to assess the disclosure of environmental aspects in sustainability report of the banking companies in Bangladesh for developing a sustainable reporting culture. Global Reporting Initiative (GRI) plays a leading role in developing guidelines in the preparation of sustainability reports. That's why GRI's standard guideline is taken into consideration. The study revealed that sustainability related information in the banking company's annual report was not sufficient enough. Moreover, in most of the cases, it was found that the information regarding sustainability reporting did not meet the standard of GRI guidelines. The study sketches the current sustainability reporting trends and practices of the banking industry in Bangladesh. Specifically, the environmental aspect of sustainability reporting is the focal point of this study. Reporting style, report size, items disclosed in the report, environmental awareness activities, and future direction related to sustainability reporting practice are also found in this study. It can help different levels of managers, organizations, stakeholders and regulatory authorities to identify issues and areas that they could be focused on to formulate future plans for making a sustainable future reporting culture in the banking sector of Bangladesh in order to make the world more sustainable.

https://universepg.com/public/storage/journal-pdf/Sustainability reporting of banking companies in Bangladesh.pdf


We train spiking deep networks using leaky integrate-and-fire (LIF) neurons, and achieve state-of-the-art results for spiking networks on the CIFAR-10 and MNIST datasets. This demonstrates that biologically-plausible spiking LIF neurons can be integrated into deep networks can perform as well as other spiking models (e.g. integrate-and-fire). We achieved this result by softening the LIF response function, such that its derivative remains bounded, and by training the network with noise to provide robustness against the variability introduced by spikes. Our method is general and could be applied to other neuron types, including those used on modern neuromorphic hardware. Our work brings more biological realism into modern image classification models, with the hope that these models can inform how the brain performs this difficult task. It also provides new methods for training deep networks to run on neuromorphic hardware, with the aim of fast, power-efficient image classification for robotics applications.


With increased awareness of environmental issues, and of ethical consumption, the fashion has been trying to address ethical issues in its supply chain, and on consumer behaviour. One approach to reducing the environmental impact of garment consumption is to change the way consumers behave. The prevailing strategies for behaviour change utilized within sustainable fashion have fallen into two categories: the provision of information, such as social media campaigns, and the creation of new garments using design strategies such as 'design for durability'. However, these strategies are based on assumptions, rather than empirical understanding of what motivates consumer garment use, or the mechanics of behaviour change. This article focuses on one particular environmentally desirable behaviour: wearing garments for longer, and the factors influencing this behaviour. The findings provide insights into where improvements could be made. A quantitative wardrobe study was undertaken with female consumers in the United Kingdom. The purpose of the study was to explore the motivations and barriers to a selection of environmentally desirable garment-use behaviours, including wearing garments for longer. From this study, behavioural motivations were compiled. The predominant factors motivating prolonged wear were comfort and good fit of garments. The predominant factor acting as a barrier was change in circumstances, which changed consumer's perceptions of how appropriate garments were for their perceived identity. The implications of these results are twofold. Changes in personal circumstances are inevitable for all consumers, and something that designers cannot influence. This suggests that alongside promoting prolonged wear, it is critical to guide consumers towards shifting ownership of unworn garments to new users. There is also an opportunity for designers and researchers to further explore comfort and fit of garments, but these factors are highly individualistic, which suggests that mass production may be detrimental to promoting prolonged wear.


It is difficult to determine the prevalence of addiction among the gay, lesbian, and bisexual population. Early studies (e.g., Fifield, 1975; Lewis, Saghir, & Robins, 1982; Saghir & Robins, 1973) suggested rates of alcoholism, or at least problematic drinking, to be around 30% or more for the lesbian and gay population, substantially higher than in the general population. These studies have, however, been widely criticized for methodological weaknesses (e.g., Beatty et al., 1999; Bux, 1996; Paul, Stall, & Bloomfield, 1991). These weaknesses included such problems as sampling primarily from patrons of gay bars, sampling only from large metropolitan areas, and inconsistent definitions of problem drinking. Later studies (McKirnan & Peterson, 1989; Skinner, 1994; Skinner & Otis, 1996) found less glaring differences in heavy alcohol and drug use between gay and lesbian and heterosexual populations; however, there were differences in patterns and consequences of use. Whether or not gay men, lesbians, and bisexual individuals are at increased risk for substance abuse, they seem to be at least using and abusing chemicals at rates comparable to those of heterosexual men and women. Bux (1996) stressed the importance of recognizing the unique needs of gay men and lesbians who may be experiencing addiction, even if prevalence rates do not suggest that they are at higher risk for problems related to abuse. Likewise, a number of authors (Beatty et al., 1999; Bux, 1996; Cabaj, 1996; Paul et al., 1991; Schaefer, Evans, & Coleman, 1987; Ubell & Sumberg, 1992) have offered specific suggestions for chemical dependency treatment that is sensitive to these unique issues. Many of these suggestions echo general recommendations for counseling gay men, lesbians, and bisexual (GLB) individuals (e.g., Eldridge & Barnett, 1991; Garnets, Hancock, Cochran, Goodchilds, & Peplau, 1991). These include such practices as adapting paperwork to allow clients the opportunity to indicate that they are GLB and to allow them to accurately identify the nature of intimate relationships (i.e., choice of life partner in addition to single, married, etc.); offering educational activities, groups, and outreach programs that are targeted toward this population; providing books and other literature specific to GLB individuals in waiting rooms and offices; and demonstrating attitudes that are not only tolerant but are affirming of GLB people. In addition, there are elements specific to addiction treatment such as familiarity with gay Alcoholics Anonymous and Narcotics Anonymous groups; assistance in connecting with sponsors who are lesbian, gay, or bisexual and recovering; staff members who are knowledgeable about the unique issues of addicted GLB people described above; understanding and assistance in striking a balance between an often very real need for secrecy regarding sexual orientation and the equally important need for honesty as part of a recovery program (and the importance of this discussion occurring in a setting in which it is safe for the individual to be fully open); and family programs that incorporate expanded definitions of family and recognize the complexities of relationships with families of origin around issues related to sexual orientation. The presence of openly GLB staff to serve as role models is also mentioned frequently. In addition, Bux (1996) stressed that it is important to be able to recognize that not all issues facing this population pertain to sexual orientation and that it is necessary to be able to differentiate when they do and when they do not. Although there is growing literature that discusses the unique concerns of GLB alcoholics and addicts, as well as the importance of an affirmative approach toward working with this population, there remains a question as to the extent to which addictions counselors are indeed doing this. Early reports (Bittle, 1982; Driscoll, 1982; Zigrang, 1982), largely anecdotal, addressed the lack of responsiveness of traditional substance abuse treatment programs to the gay, lesbian (and bisexual) population and the reluctance of this population to use them. …


In the Terri Schiavo case, different family members who want the legal authority to make decisions for Terri Schiavo have sought different treatment options - with results as opposed as life and death. Had the case not come before the courts, Michael Schiavo, Terri's husband, would have had Terri's feeding tube removed long ago; Terri's parents, Mary and Robert Schindler, if either had been named surrogate in Michael's stead, would continue feeding her indefinitely. Recognizing, as the Schiavo case highlights, that who among family members speaks for the patient can determine the course of treatment or non-treatment for a patient, it is necessary to turn renewed attention to the question of why families, whether we define them as spouses or parents, are involved in the end-of-life decisionmaking of their relatives. Are they merely a representative or even fiduciary of the patient or are they stakeholders in their own right? Do we look to family members as surrogates because they ensure a sounder process, a neutral process, for determining patient preferences and interests, or do we look to family members as surrogates because we recognize that families want to be (and perhaps should be?) involved? This paper argues that some deference to family members' own interests can be justified on the grounds of a broad notion of patient self-determination, but some degree of deference might also be justified out of respect for family members' own interests. Our law should not demand strict neutrality of these family members, but should acknowledge that their interests may have value as well. At the same time, there must be limits: the family's preferences and interests should not be allowed to overshadow those of the patient.


This study presents a new self-diagnose method for the recently developed post-IR infrared stimulated luminescence (pIRIR) dating protocols. This criterion studies the dependence of equivalent dose (De) on measurement-temperature (T) and time (t), by applying the De (t) analysis to the IRLS and pIRIR signals measured under different temperatures, and combines these De (t) plots into one, so-called the De (T, t) plot. The pattern of the De (T, t) plot is shown to be affected by anomalous fading, partial bleaching and non-bleachable signal. A De plateau can be achieved in the De (T, t) plot only when the effects of these factors are insignificant. Therefore, this plot can be used as a self-diagnose tool for the validity of pIRIR results. The De (T, t) analysis has been applied to four recently developed pIRIR protocols, using aeolian samples with different ages. The results show that this self-diagnose tool can be applied to different pIRIR protocols for validating the pIRIR dating results and evaluating the pIRIR measurement conditions.


Understanding the inner workings of deep learning algorithms is key to efficiently exploit the large number of videos that are generated every day. For the self-supervised learning of the spatiotemporal information contained within these videos, there are several types of algorithms based on convolutional neural networks (CNNs) following an auto-encoder style architecture. However, we have checked that this type of models, trained for the frame prediction task, learn jointly these spatio-temporal information, so the model is not able to recognize appearance-motion combinations not seen during training. Our proposed model, called DisNet, can learn separately the appearance and motion through disentanglement, so that it solves the generalization and scalability problems. To demonstrate this, we conducted numerous experiments under highly controlled conditions, generating specific datasets that make the "conventional" model fails for the appearance and motion classification tasks, and analyzing how well our proposal behaves under the same conditions.


Theeffects of the wheel surface condition were investigated on solidification behavior and microstructural evolution of Al-Cu eutectic ribbons. The local solidification velocity was controlled by the wheel surface condition which can be changed by either heating the wheel or coating the wheel surface with boron nitride. Theorigin of inhomogeneities in the Al-Cu eutectic ribbons both through the ribbon thickness and in the transverse plane wasalso studied. Theaverage cooling rate of the ribbon during eutectic solidification wasgreatly changedby morethan I order under the different wheel conditions, The changeof the wheel surface condition brought a variety of changes in eutectic growth morphology, It is evident that the control of the wheel surface condition is significantly important in producing the ribbons with controlled microstructures which will guarantee the reliability of the ribbon materials in practical applications,


HIV-1 integrase (IN) is essential for viral replication and offers a promising target for the development of anti-retroviral drugs. Two decades of extensive research has lead to the recent approval of raltegravir as the first IN inhibitor. Advancement of drug candidate elvitegravir, which is currently in Phase III clinical trial, has furthermore accelerated efforts against this potential target for combating HIV. However, the emergence of resistance against raltegravir and elvitegravir demands exploration of novel chemical scaffolds that could circumvent resistance against currently used HIV-1 IN inhibitors. With the goal of discovering new agents targeting HIV, a novel structural class of HIV-IN inhibitors have been designed and synthesized. Substantial computational studies were also performed that could aid the design and development of potent HIV IN inhibitors. A part of this dissertation research, covered in Chapter 3, details the design, synthesis, and biological evaluation of 3-keto salicylic acid chalcones as novel HIV-1 IN inhibitors. In the chalcone series, the most active compound, 5-bromo-2-hydroxy-3-[3-(2,3,6-trichloro-phenyl)acryloyl]-2-hydroxybenzoic acid (96) was selectively active against IN strand transfer (ST) with IC50 of 3.7 μM. While most of the compounds exhibit ST selectivity, a few were nonselective, such as 5-bromo-3-[3-(4-bromo-phenyl)-acryloyl]-2-hydroxybenzoic acid (86), which was active against both 3!-processing (3!-P) and ST with IC50 values of 11 ± 4 and 5 ± 2 "M, respectively. The compounds also inhibited HIV-1 replication with potencies comparable to their integrase inhibitory activities. Thus, compounds 96 and 86 inhibited HIV-1 replication with EC50 values of 7.3 and 8.7 "M, respectively. Chapter 4 describes the synthesis of structurally related amide derivatives which were designed by modification of the chalcone moiety. In the amide series, the most active compound, 5-bromo-3-[(3-chloro-2,4-difluoro benzyl)carbamoyl]-2-hydroxybenzoic acid (151), inhibited ST with an IC50 of 4 μM. Chapter 5 discloses the synthesis, and biological studies of halogenated phenanthrene #-diketo acids as novel HIV-1 IN inhibitors. The two most active compounds of the series, 4-(8-chlorophenanthren-3-yl)-2,4-dioxobutanoic acid (179) and 4-(6-chlorophenanthren-2-yl)-2,4-dioxobutanoic acid (177) had ST IC50 values of 1.2 and 1.3 "M, respectively, and corresponding 3!-P values of 11.0 and 5.0 "M. In the last section of the dissertation detailed in Chapter 6, computational studies were conducted with the aim of exploring the possible binding modes of potent IN inhibitors and evaluating the structural requirements for IN inhibition. To determine the physicochemical parameters important for ligand binding, in the first part of this chapter, a PHASE pharmacophore hypothesis was developed and used for molecular alignments in the initial comparative molecular field analysis (CoMFA) and comparative molecular similarity analysis (CoMSIA) 3D-quantitative structure activity relationship (3D-QSAR) modeling of the chalcone derivatives. A recent breakthrough in the field of anti-HIV research was achieved with the crystallization and 3D structure determination of a complete foamy virus IN-DNA complex. To take advantage of the power of structure-based drug design, in the second part of the computational studies, homology models of HIV-1 IN-DNA were constructed based on the foamy virus IN-DNA complex X-ray crystal structure as template through collaboration with the Oak Ridge National Laboratory. The binding modes of raltegravir and elvitegravir in our homology models were in accordance with their binding modes in their complexes with the foamy virus structure. The homology model was then used for docking and 3D-QSAR studies on our synthesized inhibitors and other integrase inhibitors including the clinically available raltegravir and elvitegravir. Free energy calculations using Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) methods were carried out to rescore and validate the binding modes of HIV-1 integrase inhibitors. 3D-QSAR models derived from this study provided detailed insights into the structural requirements for IN inhibition and established predictive tools to guide further inhibitor design. Linear interaction energy (LIE) calculations were also performed to derive energy parameters contributing to the binding free energies of the IN inhibitors in the data set. These energy parameters were also analyzed to gain insight into the binding modes of raltegravir and elvitegravir as well as to validate the conformations of our synthesized chalcone and amide derivatives. The energy terms were then used as descriptors to develop a linear interaction approximation (LIA) activity model for the inhibition of integration catalytic step. In the next section of the chapter, lead optimization was attempted using structureand ligand-based drug design tools. RACHEL, a drug optimization software, was used to design an inhibitor with desired binding interactions with the IN active site residues. The hit obtained from RACHEL was used to design a structurally related compound (157), the synthesis and activity testing of which has been described in Chapter 4. Docking studies were also performed on the phenanthrene derivatives synthesized in Chapter 5. The docking studies predominantly revealed two binding poses that were distinct from the possible binding modes of clinically used raltegravir and advanced IN inhibitor elvitegravir and, moreover, do not interact significantly with some of the key amino acids (Q148 and N155) implicated in viral resistance. Therefore, this series of compounds can further be investigated as IN inhibitors to circumvent resistance associated with current clinically used HIV-1 IN inhibitors.


Fusing emotion and cognition and my lives in and outside the academy, I tell the tale of my first encounter with ethics review. This is memory work, re-crafting scraps of writing I did over the course of almost two years to weave a story that recreates the context in which I sought answers to questions around research ethics. My focus is on how these circumstances created conflict with a model of ethical conduct enshrined in a formalised ethics review process which, I contend, undermined my ethical intentions. I conclude by arguing for a move away from a standardised view of ethics within a politicised audit culture and towards the integration of ethics with human action and conceptions of 'the good'.


• Taken together, forest tenure reform implementation in Lampung and Maluku provinces capture key issues common across different settings in Indonesia, e.g. coordination among government actors, limited government budgets and uncertainty created by changing forestry regulations. In addition, other issues that are specific to one or the other province (e.g. lack of recognition of customary rights, inadequate capacity of implementing agencies, and lack of community knowledge and awareness) are also illustrative of broader tenure challenges in other parts of Indonesia. The findings from a participatory prospective analysis (PPA) study have provided central government with better information from different sites. • Most national stakeholders, including government officials from the Ministry of Environment and Forestry who are responsible for forest reform implementation (Sub-directorate Community Forestry, Community Plantation Forest, Village Forest, and Partnership, and Forest Management Unit Division), as well as non-government stakeholders reviewed positively the sub-national action plans developed by stakeholders in Lampung and Maluku who were interested in securing local community tenure rights. These action plans emphasized multi-stakeholder collaboration (Maluku) and the strengthening of forest management units (FMUs) in Lampung, which is in line with national strategy to improve tenure reform implementation on the ground. • The outcome of PPA, including drivers of constraints to tenure security, future scenarios of tenure reform and action plans, informed a recent national-level initiative to improve forest tenure reform implementation that promises to secure local rights, e.g. Working Group of Social Forestry and government regulation (PP No 83) that shortens the process of obtaining a license for social forestry. • Perceptions among the national stakeholders indicate that the implementation of sub-national action plans aimed at securing tenure rights of local communities will be very challenging due to unclear boundaries and overlapping existing land uses among forest users. Hence, collaboration among stakeholders is key to the process. • National stakeholders agree that the PPA approach can be adopted by the Working Group of Social Forestry at province level, with a focus on increasing community awareness and ownership of reforms under the social forestry scheme, including customary forest. The PPA is not a top-down approach, it builds intimacy and strengthens communication among stakeholders. It is thus important for the working group to create a new bureaucratic culture that promotes collective action during the implementation of the Social Forestry scheme. Nining Liswanti, Esther Mwangi, Mani Ram Banjade, Tuti Herawati


Anyone trying to learn algebra and trigonometry may think they understand a concept but then are unable to apply that understanding when they attempt to complete exercises. This innovative book helps them overcome common barriers to learning the concepts and builds confidence in their ability to do mathematics. The second edition presents new sections on modeling at the end of each chapter as well as new material on Limits and Early Functions. Numerous examples are also included that provide more detailed annotations using everyday language. This approach gives them the skills to understand and apply algebra and trigonometry.


Predicting human mobility within cities is an important task in urban and transportation planning. With the vast amount of digital traces available through social media platforms, we investigate the potential application of such data in predicting commuter trip distribution at small spatial scale. We develop back propagation (BP) neural network and gravity models using both traditional and Twitter data in New York City to explore their performance and compare the results. Our results suggest the potential of using social media data in transportation modeling to improve the prediction accuracy. Adding Twitter data to both models improved the performance with a slight decrease in root mean square error (RMSE) and an increase in R-squared (R2) value. The findings indicate that the traditional gravity models outperform neural networks in terms of having lower RMSE. However, the R2 results show higher values for neural networks suggesting a better fit between the real and predicted outputs. Given the complex nature of transportation networks and different reasons for limited performance of neural networks with the data, we conclude that more research is needed to explore the performance of such models with additional inputs.


Background: The adoption of a smoke-free hospital campus policy is often a highly publicised local event. National media coverage suggests that the trend towards adopting these policies is growing, and this publicity can frequently lead hospital administrators to consider the adoption of such policies within their own institutions. Little is actually known, however, about the prevalence of these policies or their impact. Objectives: To determine the national prevalence of smoke-free hospital campus policies and the relation between these policies and performance on nationally standardised measures for smoking cessation counselling in US hospitals. Methods: 4494 Joint Commission-accredited hospitals were invited to complete a web-based questionnaire assessing current smoking policies and future plans. Smoking cessation counselling rates were assessed through nationally standardised measures. Results: The 1916 hospitals responding to the survey (43%) were statistically similar to non-responders with respect to performance measure rates, smoking policies and demographic characteristics. Approximately 45% of responders reported an existing smoke-free hospital campus policy. With respect to demographics, higher proportions of smoke-free campus policies were reported in non-teaching and non-profit hospitals. Smoke-free campus hospitals were also more likely to provide smoking cessation counselling to patients with acute myocardial infarction, heart failure and pneumonia who smoke (p<0.001). Conclusions: By February 2008, 45% of US hospitals (up from approximately 3% in 1992) had adopted a smoke-free campus policy; another 15% reported actively pursuing the adoption of such a policy. By the end of 2009, it is likely that the majority of US hospitals will have a smoke-free campus.


Preventives are sold ex ante, before disease status is realized, while treatments are sold ex post. Even if the mean of the ex ante distribution of consumer values is the same as that ex post, the shape of the distributions may differ, generating a difference between the surplus each product can extract. If, for example, consumers differ only in ex ante disease risk, then a monpolist would have more difficulty extracting surplus with a preventive than with a treatment because treatment consumers, having contracted the disease, no longer differ in disease risk. We show that the ratio of preventive to treatment producer surplus can be arbitrarily small, in particular when the distribution of consumer values has a Zipf shape and the disease is rare. The firm's bias toward treatments can be reversed, for example, if the source of private information is disease severity learned ex post. The difference between the producer surplus earned from the products can result in distorted RD the deadweight loss from this distortion can be as large as the entire producer-surplus difference. Calibrations for HIV and heart attacks based on risk factors in the U.S. population suggest that the distribution of disease risk is sufficiently Zipf-similar to generate substantial differences between producer surplus from preventives and treatments. Empirically, we find that proxies for the Zipf-similarity of the disease-risk distribution are associated a significantly lower likelihood of vaccine development but not drug development.


With the goal of studying ML along the RGB, mid-IR observations
of a carefully selected sample of 17 Galactic globular
clusters (GGCs) with different metallicity and horizontal branch
(HB) morphology have been secured with IRAC on board Spitzer:
a global sample counting about 8000 giant has been obtained.
Suitable complementary photometry in the optical and near-IR
has been also secured in order to properly characterize
the stellar counterparts to the Spitzer sources and their photospheric parameters.
Stars with color (i.e. dust) excess have been identified, their likely
circumstellar emission quantified and modelled, and empirical estimates of mass
loss rates and timescales obtained.
We find that mass loss rates increases with increasing
stellar luminosity and decreasing metallicity.
For a given luminosity, we find that ML rates are
systematically higher than the prediction
by extrapolating the Reimers law.
CMDs constructed from ground based near-IR and IRAC bands
show that at a given luminosity some stars have dusty envelopes
and others do not. From this, we deduce that the mass loss
is episodic and is ``on'' for some fraction of the time.
The total mass lost on the RGB can be easily computed by multiplying ML rates
by the ML timescales and integrating over the evolutionary timescale.
The average total mass lost moderately increases with increasing metallicity,
and for a given metallicity is systematically higher in clusters with extended blue HB.


General thin-airfoil theory for a compressible fluid is formulated as boundary problem for the velocity potential, without recourse to the theory of vortex motion. On the basis of this formulation the integral equation of lifting-surface theory for an incompressible fluid is derived with the chordwise component of the fluid velocity at the airfoil as the function to be determined. It is shown how by integration by parts this integral equation can be transformed into the Biot-Savart theorem. A clarification is gained regarding the use of principal value definitions for the integral which occur. The integral equation of lifting-surface theory is used a s the starting point for the establishment of a theory for the nonstationary airfoil which is a generalization of lifting-line theory for the stationary airfoil and which might be called "lifting-strip" theory. Explicit expressions are given for section lift and section moment in terms of the circulation function, which for any given wing deflection is to be determined from an integral equation which is of the type of the equation of lifting-line theory. The results obtained are for airfoils of uniform chord. They can be extended to tapered airfoils. One of the main uses of the results should be that they furnish a practical means for the analysis of the aerodynamic span effect in the problem of wing flutter. The range of applicability of "lifting-strip" theory is the same as that of lifting-line theory so that its results may be applied to airfoils with aspect ratios as low as three.


Through its New Energy and Industrial Technology Development Organization (NEDO) the Japanese government is sponsoring the World Energy Network (WE-NET) Program. WE-NET is a 28-year global effort to define and implement technologies needed for hydrogen-based energy systems. A critical part of this effort is the development of a hydrogen-fueled combustion turbine system to efficiently convert the chemical energy stored in hydrogen to electricity when hydrogen is combusted with pure oxygen. A Rankine cycle, with reheat and recuperation, was selected by Westinghouse as the general reference system. Variations of this cycle have been examined to identify a reference system having maximum development feasibility, while meeting the requirement of a minimum of 70, 9 percent low heating value (LHV) efficiency. The strategy applied by Westinghouse was to assess both a near-term and long-term Reference Plant. The near-term plant requires moderate development based on extrapolation of current steam and combustion turbine technology. In contrast, the long-term plant requires more extensive development for an additional high pressure reheat turbine, and is more complex than the near-term plant with closed-loop steam cooling and extractive feedwater heating. Trade-offs between efficiency benefits and development challenges of the near-term and long-term reference plant are identified. Results of this study can be applied to guide the future development activities of hydrogen-fueled combustion turbine systems.


Modern cosmology has reached an important juncture, at whic h t e ability to make measurements of unprecedented accuracy has led to conclusions that are a funda ment l challenge to natural science. The discovery that, in our current best model, the dynamics of th e Universe are completely dominated by unseen dark matter and dark energy can do little but completely alter the shape of physics research in the 21st Century. Unfortunately, much of our insight into these phen omena must come from observations of visible matter alone; this raises serious problems, as the tracing o f dark matter by visible matter is as yet poorly understood. Gravitational lensing offers strong prospects for probing the interwoven history of dark and visible matter, as mass in any form may be detected where it exists untrac ed by baryons. In this Thesis I describe advances made in the field of weak gravitational lensing, whi ch constrains the properties of the matter distribution on cosmological scales using a statistical an lysis of the coherent gravitational distortions of distant galaxy images. I summarize the development of gravi tational flexion, a higher order extension to traditional weak lensing, and describe my work done to bring the study of flexion to a stage where it may be employed to make accurate cosmological measurements. I sho w how flexion is sensitive to matter structure on smaller physical scales than existing lensing technique s and, therefore, promises to shed new light upon key untested predictions of cosmological models if it can be measured to sufficient accuracy. I discuss the success of my efforts in this direction, and describe the iss ue to be encountered in the careful analysis of this subtle gravitational signal. This research has involved advances in many areas: the calcu lation of theoretical flexion predictions, the refinement of image analysis methods for accurate galaxy sha pe estimation, and the practical application of these new flexion techniques to extragalactic imaging dat a. The culmination of these efforts is a new maximum likelihood analysis of the galaxy-galaxy lensing s ignal in theHubble Space Telescope Galaxy Evolution from Morphology and SEDs (GEMS) Survey, incorpor ating improvements and modifications necessary for the combination of flexion with traditional we ak lensing measurements. The results of this work, and particularly the extent to which measurements of fl exion provide extra cosmological insight, are discussed in detail. The conclusion is a summary of all that has been learned about the use of flexion as an accurate probe of cosmology, and a discussion of its prospects for answerin g some of the many questions that remain about dark matter. Within the next few year wide-area survey telescopes will begin imaging huge volumes of deep space, with the measurement of the gravitational len sing signal being given high priority in the analysis of these data. Within this context, the primary inq u ry of this Thesis is the extent to which the application of flexion measurement techniques will help she d n w light upon the unseen, and currently poorly understood, components of the Universe.


We study the problem of Safe Policy Improvement (SPI) under constraints in the offline Reinforcement Learning (RL) setting. We consider the scenario where: (i) we have a dataset collected under a known baseline policy, (ii) multiple reward signals are received from the environment inducing as many objectives to optimize. We present an SPI formulation for this RL setting that takes into account the preferences of the algorithm's user for handling the trade-offs for different reward signals while ensuring that the new policy performs at least as well as the baseline policy along each individual objective. We build on traditional SPI algorithms and propose a novel method based on Safe Policy Iteration with Baseline Bootstrapping (SPIBB, Laroche et al., 2019) that provides high probability guarantees on the performance of the agent in the true environment. We show the effectiveness of our method on a synthetic grid-world safety task as well as in a real-world critical care context to learn a policy for the administration of IV fluids and vasopressors to treat sepsis.


Addressing discrimination within the professional sphere is becoming ever more important in French public debate in both the legal and managerial fields. A number of the 18 grounds of discrimination recognised under French law such as gender and ethnicity have been widely discussed in the scientific literature. However, unlike studies undertaken in English-speaking countries, few French-speaking researchers have explored age discrimination. This issue warrants analysis insofar as the actual economic context has forced governments to encourage more people to remain in the labour market. This objective, however, has proven difficult to achieve. A critical question is whether age-related labour market participation gaps depend on individual characteristics. If not, other factors might come into play, including possible discrimination. First, we review the employment of older workers over time. We then use econometric methods to assess the nature of labour market participation gaps and analyse their relationship with business cycles. With regard to the latter point, our findings reveal differences between men and women.


We address one-shot imitation learning, where the goal is to execute a previously unseen task based on a single demonstration. While there has been exciting progress in this direction, most of the approaches still require a few hundred tasks for meta-training, which limits the scalability of the approaches. Our main contribution is to formulate one-shot imitation learning as a symbolic planning problem along with the symbol grounding problem. This formulation disentangles the policy execution from the inter-task generalization and leads to better data efficiency. The key technical challenge is that the symbol grounding is prone to error with limited training data and leads to subsequent symbolic planning failures. We address this challenge by proposing a continuous relaxation of the discrete symbolic planner that directly plans on the probabilistic outputs of the symbol grounding model. Our continuous relaxation of the planner can still leverage the information contained in the probabilistic symbol grounding and significantly improve over the baseline planner for the oneshot imitation learning tasks without using large training data.


Credibility is a determinative factor in many of the immigration cases adjudicated every year (and, each year, the federal immigration agency adjudicates hundreds of thousands of cases). Given the numbers of affected immigrants and the stakes involved, it is essential that the legislature, agency, and courts employ a well-grounded framework for assessing credibility. In a previous article, I analyzed the then recently enacted REAL ID Act credibility amendments to the Immigration and Nationality Act. This article builds on the previous analysis by discussing the rules and guiding principles recently established by the federal courts of appeals that now govern the adjudication of credibility determinations under the REAL ID Act in certain jurisdictions. Specifically, precedential decisions in the federal courts of appeals have focused on the incorporation of a rule of reason test into credibility determinations, the role that "trivial" inconsistencies play in credibility determinations, and the importance of demeanor in an assessment of credibility. The purpose of addressing these rules and guiding principles is threefold. The first goal is to examine whether they are congruent with the REAL ID Act specifically, and credibility determinations generally. Second, in providing an objective assessment, this article seeks to aid immigration adjudicators and reviewing bodies, either by explaining further the implications of rules that have already been established in a jurisdiction, or by answering the question of whether and how to employ them in jurisdictions that have not yet adopted them. Lastly, this article will highlight some of the issues regarding credibility determinations that apply, to a certain extent, to all agency proceedings where credibility is at issue, and even to those outside the agency context. The express credibility findings required of immigration judges provide a unique window into the "black box" of the decision-making process that often surrounds the credibility assessments of triers of fact.


The multilayer coupled wave theory is extended to systematically investigate the diffraction properties of multilayer volume holographic gratings (MVHGs) under ultrashort laser pulse readout. Solutions for the diffracted and transmitted intensities, diffraction efficiency, and the grating bandwidth are obtained in transmission MVHGs. It is shown that the diffraction characteristics depend not only on the input pulse duration but also on the number and thickness of grating layers and the gaps between holographic layers. This analysis can be implemented as a useful tool to aid with the design of multilayer volume grating-based devices employed in optical communications, pulse shaping, and processing.


Drones have become ubiquitous in performing risky and labor intensive areal tasks cheaply and safely. To allow them to be autonomous, their flight plan needs to be pre-built for them. Existing works do not precalculate flight paths but instead focus on navigation through camera based image processing techniques, genetic or geometric algorithms to guide the drone during flight. That makes flight navigation complex and risky. In this paper we present automated flight plan builder DIFPL which pre-builds flight plans for drones to survey a large area. The flight plans are built for subregions and fed into drones which allow them to navigate autonomously. DIFPL employs distributed paradigm on Hadoop MapReduce framework. Distribution is achieved by processing sections or subregions in parallel. Experiments performed with network and elevation datasets validate the efficiency of DIFPL in building optimal flight plans.


The purpose of this research is to analyze social practices in the work of community health agents (ACSs) in the city of Recife, state of Pernambuco, Brazil. Accordingly, a qualitative approach was adopted, whose theoretical-methodological aspects were founded on historical and dialectic materialism. ACSs have a unique role, because they deal with an important crosssection of social classes in their work and living spaces. Despite the institutionalization of their work, it still contains references forged during their work with the community and the population at large. We emphasize that the institutionalization of the work of ACSs, in and of itself, is a contradictory and conflicting process from the standpoint of institutional policy, since the practice developed by them incorporates popular wisdom and practices that may create tensions. At the same time, it is important to remember that the territory where the ACSs live and operate exerts an influence on their professional production.


Introduction National guidelines state that health care professionals (HCPs) should advise patients on the importance of maintaining a healthy weight. Firefighters have high rates of obesity, and cardiovascular events are the leading cause of line-of-duty deaths in firefighters. This study assessed the association of age and body mass index (BMI) with HCP weight recommendations among male firefighters. Methods We used data on self-reported HCP weight recommendations and measured BMI from a 2011–2012 national sample of male firefighters (N = 1,002). HCP recommendations were recorded as no advice, maintain, gain, or lose weight, and BMI was categorized as normal (<25.0 kg/m2), overweight (25.0–29.9 kg/m2), class I obese (30.0–34.9 kg/m2), and class II or III obese (≥35.0 kg/m2). We used multinomial logistic regression to estimate the odds of receiving weight advice by age and BMI categories. Results Most firefighters (96%) reported visiting an HCP in the past year. Most (69%) firefighters and 48% of class I to III obese firefighters reported receiving no weight advice. Higher BMI predicted HCP advice to lose weight (odds ratio class I obese vs normal weight: 12.98; 95% confidence interval: 5.38–31.34). Younger firefighters were less likely to receive weight loss advice than older firefighters, except among those who were class II or III obese. Conclusions HCPs are important sources of health information for firefighters. Overweight and obese firefighters, particularly those who are younger, do not consistently receive HCP advice to lose weight. This marks a missed opportunity to prevent further weight gain and reduce obesity-related health outcomes.


AbstractThe article presents an analytical review of the literature data on the impact of hypobaric hypoxia on the human body and the results of their own pilot studies of hypobaric hypoxic adaptation in children with neuropsychiatric diseases.
Purpose: to evaluate the effect of hypobaric hypoxic adaptation on emotional, speech disorders in children with various neurological pathologies due to perinatal damage of the central nervous system.
Materials and methods: The study involved 31 patients aged from 6 months to 16 years, the median age was 1.5 years. The spectrum of neurological disorders in patients: cerebral palsy (n=9), epilepsy (n=10), impaired psychomotor development (n=12). All children had a sleep disorder, increased emotional lability and impaired speech function. All the patients included in the study underwent a course of moderate hypobaric hypoxytherapy, which consisted of 15 sessions.
Results: The study found significant improvement in the quality of life (p<0.001) with normalization of sleep in 87.1% (n=27), improvement in emotional activity in 80.6% (n=25) (p<0.001), social activity in 64.5% (n=20) (p<0.05), cognitive activity in 58.1% (n=18) (p<0.001). Dynamic assessment of neurological status showedpositive changes in 19.4% (n=6) of patients, with decreased muscle tone and improved coordination in children with cerebral palsy (level 2-3 GMFCS). Among children under the age of 1.5 years with delayed psychomotor development due to perinatal damage of the central nervous system and prematurity, 66.6% (4 cases) noted the acquisition of new motor stages, and according to the results of their neurosonography with doppler sonography, all cases showed normalization of cerebral hemodynamic parameters.
Conclusion: Adaptation to hypoxia is a pathogenetically substantiated non-drug method for the prevention and treatment of diseases of the nervous system in children, allowing to activate the reserve capabilities of the body with insufficient effectiveness of drug therapy.


In May 2007, the Supreme Court decided Bell Atlantic Corp. v. Twombly and sent shockwaves throughout the federal civil justice system. Twombly has triggered an avalanche of motions to dismiss, which, in turn, have generated thousands of judicial opinions, some of them knee-jerk reactions, other more thoughtful. It also has generated a plethora of academic commentary, much of it shrill and negative.As the fourth anniversary of the Twombly decision approaches, the time for venting is over. Twombly is the law of the land; and the Supreme Court, having affirmed that decision in Iqbal, is not likely to shift course. Nor is the Advisory Committee likely to act absent empirical data showing that cases which would survive Rule 12(b)(6) motions prior to Twombly are now being dismissed. The likelihood of congressional action is even more remote. In short, the legal community is going to have to live with the Twombly holding and probably for a long time. Still, the scope of Twombly remains unsettled and "[p]leading standards in federal litigation are in ferment. This article will explore how trial courts can adhere to Twombly's core concerns — not allowing speculative claims to open the door to potentially costly discovery and draining of judicial resources by dismissing those complaints "that merely create a suspicious [of] a legally cognizable right of action," while at the same time remaining true to the goals of the Federal Rules of Civil Procedure that meritorious litigants shall have their day the court.Among other things, I suggest that (1) the courts apply a proportionality standard in passing on pleadings under Twombly; (2) the courts be circumspect in dismissing cases on the pleadings where information is the exclusive control of the defendants and no discovery has been had; (3) courts as a general rule dismiss claims without prejudice; and (4) the courts avoid the pitfalls of the fact/conclusion dichotomy experienced at common law and under the codes. The article also explores the perverse (and unintended) effect of Twombly may be more discovery and even fewer trials.


Computer architecture concentrates on the logical aspects of computer design as opposed to the physical or electronic aspects. The underlying logical design of most modern computers is still based on that of the earliest electronic computers despite decades of progress in electronic circuitry. the innovations that have occurred in computer architecture have been driven by two different goals: higher performance and lower cost. Performance driven improvements have yielded computer systems with increasingly higher computation speeds and throughput. Cost driven improvements have yielded systems that are easier to use and applicable to a broader range of automatic control problems. Improvements in electronic circuitry have not led directly to architectural innovations; computers that pioneered new circuit technologies usually relied on older architectural concepts.


This thesis is based on a journey towards developing team working within a primary healthcare setting which enabled the NHS agenda for primary care service delivery to keep pace with the government modernisation agenda. (Department of Health, 1997). Initially the focus was on the development of an integrated nursing team which enabled all disciplines of nurses to work towards a patient focussed healthcare service, but it soon became evident that all staff involved in delivering the primary healthcare service were essential to the process and developments of the enquiry if the objective was to be achieved.
An action enquiry approach based on collaborative and participative action research (Carr and Kemmis, 1986; Lincoln and Guba, 1989; Cayer, 1997) was discussed and was the prime method of enabling changes to occur in the healthcare practice. This is represented by the interrelated four main cycles of enquiry that have emerged from the data, and discussed in this thesis.
Key to the success of the developments was an understanding of team working and leadership as it applied within a healthcare setting and also the underlying dynamics, which are evident when different professional groups from different traditions and knowledge base work together. (Schon, 1983) This was explored within the context of a systems approach to organisational development and through reflective dialogue along the principles advocated for creating a learning organisation. (Senge, 1990)
This thesis will demonstrate how confidence developed in myself and the practitioners, especially those from marginalised groups, and how the wider healthcare system made an impact on the developments within the practice. The area of leadership will be discussed from multiple perspectives and recognition that as a concept all stakeholders had a poor understanding of leadership.
The key finding from this study identifies the need for a holistic approach to manage and sustain change, and indeed everyday productive working relationships. This especially identifies the importance of giving attention to the preparation of future healthcare workers, the appropriateness of organisational structures in which services are delivered and support structures available to those in team leadership positions


In this paper we introduce a novel method that can efficiently estimate a family of hierarchical dense sets in high-dimensional distributions. Our method can be regarded as a natural extension of the one-class SVM (OCSVM) algorithm that finds multiple parallel separating hyperplanes in a reproducing kernel Hilbert space. We call our method q-OCSVM, as it can be used to estimate q quantiles of a high-dimensional distribution. For this purpose, we introduce a new global convex optimization program that finds all estimated sets at once and show that it can be solved efficiently. We prove the correctness of our method and present empirical results that demonstrate its superiority over existing methods.


Roland Boer's work on the sacred economy of ancient Israel will become a standard reference volume for years to come. Boer reframes our understanding of Israel's economy around Marx's notion of regulation, the distinction between allocative and extractive economies, and patterns of subsistence survival at the village level. While this response celebrates Boer's work, it suggests that more attention be given to the negative aspects of extraction economies, in particular to subsistence survival, and to the role of women and children in this economy. It also notes that Boer's description of wisdom literature as reflecting the voices of the ruling elite in their attempt to control the servant class might be balanced by more attention to the wisdom literature where God becomes an advocate for the poor.


In this paper, we present an open source Error-Correcting Output Codes (ECOC) library. The ECOC framework is a powerful tool to deal with multi-class categorization problems. This library contains both state-of-the-art coding (one-versus-one, one-versus-all, dense random, sparse random, DECOC, forest-ECOC, and ECOC-ONE) and decoding designs (hamming, euclidean, inverse hamming, laplacian, β-density, attenuated, loss-based, probabilistic kernel-based, and loss-weighted) with the parameters defined by the authors, as well as the option to include your own coding, decoding, and base classifier.


Background:We hypothesized that polymorphic mutations exist that are associated with the emergence of the multinucleoside resistance mutations (MNR), 69 insertion and Q151M. Methods:The Swiss HIV Cohort Study was screened, and the frequencies of polymorphic mutations in HIV-1 (subtype B) were compared between patients detected with the 69 insertion (n = 17), Q151M (n = 29), ≥2 thymidine analogue mutations (TAM) 1 (n = 400) or ≥2 TAM 2 (n = 249). Logistic regressions adjusted for the antiretroviral treatment history were performed to analyze the association of the polymorphic mutations with MNR. Results:The 69 insertion and TAM 1were strongly associated and occurred in 94.1% (16 of 17) together. The 69 insertion seemed to emerge as a consequence of the TAM 1 pathway (median years until detection: 6.8 compared with 4.4 for ≥2 TAM 1, P Wilcoxon = 0.009). Frequencies of 8 polymorphic mutations (K43E, V60I, S68G, S162C, T165I, I202V, R211K, F214L) were significantly different between groups. Logistic regression showed that F214L and V60I were associated with the emergence of Q151M/TAM 2 opposed to 69 insertion/TAM 1. S68G, T165I, and I202V were associated with Q151M instead of TAM 2. Conclusions:Besides antiretroviral therapy, polymorphic mutations may contribute to the emergence of specific MNR mutations.


The work presented in this thesis is concerned with the characterisation of the UL32 gene of herpes simplex virus type 1 (HSV-1). UL32 encodes an essential 596 amino acid cysteine-rich, zinc-binding protein that is highly conserved throughout the herpesviruses. The UL32 protein is essential for the cleavage of concatemeric viral DNA into monomeric genomes and their packaging into preformed capsids. Conservation is highest at the C-terminus and three CxxC motifs are present in almost all known herpesvirus UL32 sequences
The UL32 antibodies available in the laboratory at the beginning of the project were incapable of detecting small amounts of UL32 protein and so new rabbit antisera were created. Soluble extracts from insect cells infected with a UL32-expressing baculovirus (AcUL32) were fractionated by anion exchange chromatography and the UL32-containing fractions used to immunise rabbits. The resultant antisera successfully recognised UL32 from transfected, HSV-1 infected and baculovirus infected cells on western blots, and UL32 in transfected cells by immunofluorescence.
I performed random mutagenesis of the UL32 gene in an effort to examine structure-function relationships within this protein, and generated a panel of 37 mutants containing 5 amino acid insertions at distinct positions. The abilities of these mutants to complement the DNA packaging and growth defects of a virus lacking a functional copy of UL32 (the null mutant hr64) were examined and 15 of the mutants retained functionality in both assays. A complete correlation was found between the ability of mutants to support growth and DNA packaging, suggesting that the key functions of UL32 are confined to the DNA packaging pathway. There was also good correlation with the degree of amino acid conservation within UL32, with most of the mutants which abolished functionality being located in the highly conserved regions, and the functional mutants in less conserved regions. A number of site-specific mutants were also created, in which the paired cysteine residues were replaced with serines (i.e. CxxC to SxxS). Mutation of the first and third cysteine pairs (from the N-terminus) completely abrogated growth and packaging, whereas significant functionality was maintained following mutagenesis of the central pair. Finally, removal of the C-terminal 4 amino acids also resulted in generation of a non-functional protein.
Generation of an HA-tagged UL32 construct and the introduction of this into HSV-1 allowed the localisation of UL32 in infected cells to be studied. In contrast to previous reports, I detected UL32 predominantly in the nuclei of infected cells, co-localising with ICP8 in replication compartments. DNA packaging has previously been shown to occur within the replication compartments and a number of the other packaging proteins also localise to these sites. It was previously reported that UL32 played a role in the localisation of capsids to the replication compartments. However, work presented in this thesis shows this not to be the case, and that capsid proteins VP5 and VP19C were correctly localised in replication compartments during infections with the UL32 mutant hr64. I found no evidence of UL32 interaction with the UL6, UL25 or UL17 DNA packaging proteins in HSV-1 infected or transfected cells, or using immunoprecipitation from baculovirus-expressed cells.
Immunofluorescence studies of co-transfected cells showed that UL15 could direct the partial re-localisation of UL32 from the cytoplasm to the nucleus. The addition of the other terminase subunits UL28 and UL33 caused the complete re-localisation of UL32 to the nucleus, suggesting that UL32 might interact with the terminase complex. Fifteen of the insertional mutants were completely re-localised to the nucleus in the presence of UL15, UL33 and UL28, with eleven further mutants showing an intermediate phenotype of partial nuclear localisation. The ability to at least partially co-localise with the terminase complex appeared necessary for the ability of the mutants to support virus growth and DNA packaging, suggesting that this interaction may be essential for the function of UL32. However, no interaction could be demonstrated between UL32 and any of the individual terminase subunits using immunoprecipitation from insect cells.
A series of experiments was undertaken to further characterise the UL32 protein. A new UL32 mutant virus (Δ32EP) was generated by insertion of a kanamycin resistance cassette in place of a large portion of the UL32 gene. This mutant had an indistinguishable phenotype from hr64, confirming that the main function of UL32 is within DNA packaging. The functional conservation between HSV-1 UL32 and the homologues from HCMV and VZV was examined, but neither protein could support the growth of Δ32EP. DNA fragments from replicated concatemeric DNA from Δ32EP infected cells behaved similarly to wt HSV-1 fragments in PFGE, suggesting that UL32 is not involved in the resolution of branched structures within the genome prior to packaging.
UL32 had previously been reported to bind zinc, and this was confirmed using a zinc-release colourimetric assay. The amount of zinc bound to soluble baculovirus-expressed UL32 was quantified, showing that UL32 bound zinc in a 1:1 molar ratio. UL32 does not share all of the characteristics of a zinc finger motif, but the results of the mutagenesis experiments suggest that the outer CxxC/CxxxC motifs may be important for zinc binding.
Because of its zinc-binding properties and potential interaction with the terminase complex, the DNA binding properties of UL32 were also investigated. It was found that UL32 did not bind to dsDNA containing either the minimal packaging sequence (Uc-DR1-Ub) or an unrelated non-HSV-1 sequence using an electrophoretic mobility shift assay (EMSA).


The de facto steward of U.S. patent law is the United States Court of Appeals for the Federal Circuit, which is the exclusive appellate venue for patent cases. As the perceived importance of the patent system has steadily increased since the court's formation in 1982, the Federal Circuit's performance has been closely followed by an ever-expanding group of practitioners, academics, and other interested observers, who have not been shy about pointing out the court's deficiencies. Common complaints about the Federal Circuit's case law and the quality of its decision-making include: panel-dependency, formalism, indeterminacy, and the over- or under-enforcement of certain doctrines. The academic literature offers a variety of proposals for remedying or compensating for the Federal Circuit's perceived shortcomings, such as having specialized patent trial judges, expanding the number of circuit courts that hear patent appeals, and modifying the Federal Circuit's jurisdiction.Compared to existing proposals, this Article takes a different approach to analyzing the Federal Circuit's problems by focusing primarily on the judges themselves and their adjudicatory environment. Lessons from cognitive psychology, management science, and the literature on judicial behavior suggest that many of the complaints about the court are potentially grounded in, or at least aggravated by, the expertise developed by the judges and the internal dynamics of the court, which may adversely affect the Federal Circuit's ability to reconsider its precedents in a timely manner. This Article explores how the Federal Circuit, in its current form, may have difficulty self-correcting, and proposes that a solution may lie in staffing the Federal Circuit with only district judges who serve staggered terms of limited duration.


This volume presents an analysis of Russian case from a sign-oriented perspective. The study was inspired by William Diver's analysis of Latin case and follows the spirit of the Columbia School of linguistics. The fundamental premise that underlies this volume is that language is a communicative tool shaped by human behavior.In this study, case is viewed as a semantic entity. Each case is assigned an invariant meaning within a larger semantic system, which is validated through numerous examples from spoken language and literary texts to illustrate that the distribution of cases is semantically motivated and defined by communicative principles that can be associated with human behavior.


A POLICE/PROBATION PARTNERSHIP: ONE CITY'S RESPONSE TO SERIOUS, HABITUAL JUVENILE OFFENDING Kimberly D. Hassell University o f Nebraska at Omaha, 2000 Adviser: Edward R. Maguire, Ph.D. The purpose of this study is to explore a police/probation collaboration in a large Western police department. While many of these collaborative approaches to crime and disorder have been formed, there has been scant empirical research conducted on their effectiveness. As such, this study explores the implementation and impact o f a formal collaboration on both the police and probation departments, the juveniles targeted by the collaboration and the local juvenile justice system. In addition, this thesis addresses whether police and probation departments can maintain coordinating relationships to equitably, efficiently and effectively control delinquency in one Western city. This study is mainly qualitative in that observations and unstructured interviews provide most o f the data. This qualitative analysis is based on 105 hours o f fieldwork and 34 unstructured interviews between January 26, 2000 and February 10, 2000. Quantitative agency data were also collected for descriptive analyses of the program's selection process, as well as the types o f juveniles participating in the program. The findings from this study suggest that the police/probation collaboration in Doggington operates inside an exchange system. As such, the collaboration has mended strained relationships between the police and probation departments. Tn addition, the collaboration is impacting both the juveniles participating in the program, as well as the local juvenile justice system. The analysis o f Doggington's police/probation collaboration provides an excellent example o f how two interdependent criminal justice agencies dealt with their conflicting ideologies and effectively coordinated in order to produce what appear to be equitable, efficient, and, possibly, effective results.


Abstract Garnetiferous pelitic to psammopelitic migmatites widespread across the central and eastern part of the Aravalli–Delhi Fold Belt in NW India record two distinct orogenies, e.g. the Aravalli Orogeny (1.7–1.6 Ga) and the Delhi Orogeny (1.0 Ga). In this study, we integrate field geological studies with textural and mineral–chemical analyses, P–T pseudosection modelling and in situ monazite dating in anatectic migmatites in the Aravalli Supergroup occurring along the Deoli–Shahpura segment. The study reveals formation of peak assemblages of garnet + sillimanite + biotite + K-feldspar + melt and garnet + muscovite + K-feldspar + melt in two anatectic migmatite samples. P–T pseudosection modelling suggests that anatexis in the gneisses occurred at ~8 kbar and 700–800°C along a tight-loop clockwise P–T path. Monazite ages from the migmatites indicate that the anatexis occurred at ~1.73–1.74 Ga. This age is similar to the Palaeoproterozoic anatexis (at 7–8 kbar) and charnockite emplacement in the Sandmata and the Mangalwar complexes, the subsolidus amphibolite-facies metamorphism in the Rajpura–Dariba and Pur–Banera supracrustal belts, and the A-type granite magmatism in the North Delhi Fold Belt. We propose that the Palaeoproterozoic migmatites in central and eastern Rajasthan are part of the one crustal unit that underwent anatexis during an accretion event along the NE–SW-trending Aravalli orogenic belt.


The Special Sensor Ultraviolet Spectrographic Imager (SSUSI) is currently slated for launch on the Defense Meteorological Satellite Program (DMSP) F-16 in November 2001. This instrument consists of a scanning imaging spectrograph (SIS) whose field-of-view is scanned from horizon-to-horizon and a nadir-looking photometer system (NPS). It will provide operational information about the state of the atmosphere above 100 km. The unique problems incurred by the observational requirements (e.g. that we be able to make daytime and nighttime observations) and the design trade-offs needed to meet those requirements were strong drivers on calibration requirements. Those design trade-offs and the expectation that the instrument calibration will change appreciably in-flight have led to the requirement to perform a large instrument characterization in-flight using only natural sources. We focus, in this paper, on the flight characterization of the SSUSI instrument. This includes discussions of the stellar calibration approach for radiometric calibration, measurements of internally scattered light, sensitivity to the South Atlantic Anomaly, measurements of changing pulse height distributions, and measuring changing reflectivity of a nadir viewing scan mirror. In addition, the calibration of the NPS system using natural sources is addressed.


While previous studies have documented the internal structures of English lexical bundles (LBs) in a range of academic genres, how such fragmentary phrases are used in context has been given little attention. The current study addresses this gap by investigating to what extent three different writer groups, i.e., L1-English freshman students, L1-Korean freshman students, and published research article authors, integrate LBs into their English academic writing. The study first categorizes the LBs by their three main structures: VP-, NP-, and PP-based. It then focuses on the syntactic roles of the bundles in context, and plots these roles onto the developmental stages of grammatical complexity proposed by Biber, Gray, and Poonpon (2011). The results show a progressive sequence of native and nonnative apprentice writers' use of LBs toward being proficient academic writers, while also demonstrating that some features are unique to each group. The study extends the structural analysis of LBs in the literature by providing new information on the grammatical status of LBs in context and in relation to their uses by different groups of writers.


The UK economy has experienced significant macroeconomic adjustments following the 2016 referendum on its withdrawal from the European Union. This paper develops and estimates a small open economy model with tradable and non-tradable sectors to characterise these adjustments. We demonstrate that many of the effects of the referendum result can be conceptualised as news about a future slowdown in productivity growth in the tradable sector. Simulations show that the responses of the model economy to such news are consistent with key patterns in UK data. While overall economic growth slows, an immediate permanent fall in the relative price of non-tradable output (the real exchange rate) induces a temporary 'sweet spot' for tradable producers before the slowdown in tradable sector productivity associated with Brexit occurs. Resources are reallocated towards the tradable sector, tradable output growth rises and net exports increase. These developments reverse after the productivity decline in the tradable sector materialises. The negative news about tradable sector productivity also leads to a decline in domestic interest rates relative to world interest rates and to a reduction in investment growth, while employment remains relatively stable. As a by-product of our analysis, we provide a quantitative analysis of the UK business cycle.


Our main result states that a finite semiring of order > 2 with zero which is not a ring is congruence-simple if and only if it is isomorphic to a "dense" subsemiring of the endomorphism semiring of a finite idempotent commutative monoid. We also investigate those subsemirings further, addressing e.g. the question of isomorphy.


One-to-one computing has been proposed as one solution for improving primary school education around the world. Ukombozi School is a public primary school in Mkimbizi village, Tanzania, and the school has performed outstandingly on the district, regional, and national levels. Ukombozi school has 100 XO-1 "children's laptops", and, in collaboration with a local university, the school is using those computers for teaching pupils basic computer literacy. The school, however, has ambitious plans for the computers. This paper analyses the necessary steps for developing the current research and design collaboration into a fully-fledged living lab, which can be used to studying, further developing, and replicating Ukombozi School's success.


The paper presents an in depth assessment of different similarity laws for the mean velocity profile in zero pressure gradient (ZPG) turbulent boundary layers (TBL's) in comparison with mostly experimental and few computational data. The emphasis is on the descriptions which are complete in the sense that a full representation of the mean velocity profile, its streamwise evolution and all integral parameters, including the friction factor and the shape factor, are provided as a function of Reynolds number. The first such complete description is the classical two-layer theory with its characteristic logarithmic mean velocity profile in the region where the two layers overlap, henceforth referred to as the "log law." The main alternative scalings which have been proposed over the last decade have led to power law descriptions of the turbulent mean velocity profile. Since the different descriptions were calibrated with different data sets, the controversy over the relative merits of the different approaches has lingered on. The purpose of the present paper is to measure the principal competing theories against the same vast data set of more than 300 mean velocity profiles from more than twenty different sources. The results confirm the conclusions of numerous authors that the log law provides a fully self-consistent and accurate description of all the mean quantities and demonstrates conclusively that the same cannot be achieved by the competing power law theories. Along the way, it is also argued that the traditional description of the outer velocity profile in terms of a wall-normal coordinate normalized to unity at a hypothetical boundary layer "edge" delta and a "wake parameter" Pi is not robust with respect to the fit of the outer velicity profile and should therefore not be used in theoretical arguments. (C) 2008 American Institute of Physics.


Notwithstanding the ambiguous research and productivity promoting effects of plant variety protections (PVPs), even in developed countries, many developing countries have adopted PVPs in the past few years to comply with their Trade-Related Aspects of Intellectual Property Rights (TRIPS) obligations. Seeking and maintaining PVPs reserves options to an expected revenue stream from the future sale of protected varieties, the value of which varies for a host of reasons. In this paper we empirically examine the pattern of plant variety protection applications in China since its PVP laws were first introduced in 1997. We place those PVP rights in the context of China's present and likely future seed markets to identify the economic incentives and institutional aspects that influence decisions to develop and apply for varietal rights.


In 1998, five major companies (Ericsson, Nokia, IBM, Toshiba and Intel) formed a group to create a license-free technology for universal wireless connectivity in the handheld market. The result is Bluetooth, a technology named after a 10th-Century king who brought warring Viking tribes under a common rule. The Bluetooth specifications (currently in version 1.1) define a radiofrequency (RF) wireless communication interface and the associated set of communication protocols and usage profiles. The link speed, communication range and transmission power level for Bluetooth were chosen to support low-cost, power-efficient, single-chip implementations of the current technology. In fact, Bluetooth is the first attempt at making a single-chip radio that can operate in the 2.4-GHz ISM (industrial, scientific and medical) RF band. While most early Bluetooth solutions are dual-chip, vendors have recently announced single-chip versions as well. In this overview of the technology, I first describe the lower layers of the Bluetooth protocol stack. I also briefly describe its service discovery protocol and, finally, how the layers of the protocol stack fit together from an application's point of view.


Doubts have often been expressed about computer-assisted research on literature, but until about seven years ago these doubts were voiced mainly by those who did not themselves practice it.(1) Since 1988, however, real worries have increasingly been expressed by specialists in books and periodicals devoted to computer-assisted research on literature (henceforth CARL). They ask questions not only about methods, but, more seriously, about the assumptions behind the methods. These questions are starting to be put with a harshness unprecedented in CARL. Thus Willie van Peer, in a 1989 article in Computers and the Humanities, goes so far as to say that the view of language underlying quantitative studies is "utterly naive" (303), while in 1991, in Literary and Linguistic Computing, Thomas Corns talks of certain hopes for CARL as resembling a "fanatic's dream" (128). These doubts have culminated in a recent special issue of Computers and the Humanities (1993-94) in which contributors call still more urgently for internal revaluation and ask more pressingly than before whether CARL should not be moving in new directions. During these last seven years, CARL researchers have voiced a special unease about the fact that almost all literary critics of repute ignore the results of CARL investigations. This unease was first highlighted in a colorful and provocative article by Rosanne Potter ("Literary Criticism"), and the recent special issue of Computers and the Humanities once more points out that in its present form CARL is marginalized by most literary critics.(2) The CARL experts who have asked why this should be so have usually provided what is no doubt the correct answer: that the conclusions of most individual CARL projects have simply been too trivial or too obvious to attract attention.(3) A second reason put forward for the marginalization of CARL is the rebarbative presentation of its research; this is a particular concern of Potter's ("Literary Criticism" 91, 94, 97), but others have echoed her. There may be a third contributory factor, one that has not yet been singled out by any practitioner nor, I believe, by external critics. Some surprising figures of speech infiltrate the critical diction of many CARL analysts - figures of speech that tend to mythologize their own enterprises. This self-mythologization is, perhaps, both a symptom and a cause of the problem. It may have stopped CARL experts evaluating properly the results of their own research, and it cannot but be off-putting to the non-CARL critics they are trying to win over. It is perhaps natural that some CARL experts should see themselves as pioneers or navigators, going downstream to check information at the confluence of the valleys and fortunately not looking upstream at all the vertiginous tasks ahead: We therefore had to go back downstream from the Dictionary of Frequencies, and extract information very close to the source, at the foot of the texts, at the confluence of 15 valleys where the raw forms of the 15 chronological sections converged [...] upstream, how many tasks were waiting - tasks which might have made us dizzy if we had looked far enough ahead. Luckily fog swathed our departure. Or: [T]he present study constitutes an entree en matiere, a first voyage into the quantitatively uncharted waters of contemporary narratological pragmatics. (Frautschi 280) But it is rather more surprising to find them as mountaineers: Will imitators be braver than precursors were - will they follow up the steep slope Gunnel Engwall has embarked on? Or as horse-riders: As an experienced rider controls his horse with ever more subtle commands, so the critic may control the exact routines of the computer with more latitude. (Smith 39) Or as big-game hunters: [Computer-knowledge is] unrestrained curiosity, drawing people to safaris in the jungles of the unknown. (Busa 71) They may even share this outdoor life with their chosen authors: certain stylo-statistical tests show that Marlowe is like a "young Olympic quality athlete" who "may dominate the track in all events" (Baker 37). …