Abstract Study Objectives Sleep is essential to young people's wellbeing, yet may be constricted by the adolescent delayed sleep phase coupled with school start times. COVID-19 restrictions caused major disruptions to everyday routines, including partial school closures. We set out to understand changes in students' self-reported sleep quality, and associations with mental wellbeing and interpersonal functioning, during these restrictions. Methods The OxWell school survey—a cross-sectional online survey—collected data from 18 642 children and adolescents (aged 8–19 years, 60% female, school year 4–13) from 230 schools in southern England, in June–July 2020. Participants completed self-report measures of the impact of COVID-19 restrictions on sleep quality, happiness, and social relationships. Sleep timing was compared with data collected from 4222 young people in 2019. Results Females and older adolescents were more likely to report deteriorations in sleep during the national lockdown. Regression analysis revealed that changes in happiness (β = .34) and how well students were getting on with others in their household (β = .07) predicted change in sleep quality. Students' bedtimes and wake times were later, and sleep duration was longer in 2020 compared to the 2019 survey. Secondary school students reported the greatest differences, especially later wake times. Conclusions During COVID-19 restrictions, sleep patterns consistent with adolescent delayed sleep phase were observed, with longer sleep times for secondary school students in particular. Perceived deteriorations in sleep quality were associated with reductions in happiness and interpersonal functioning, highlighting the importance of including sleep measures in adolescent wellbeing research.


Over the past several years there have been repeated analyses of the potential value of petascale bioinformatics and computational biology applications, as well as analyses of the system engineering steps required to implement applications and systems at such scale. Most recently and notably, Snavely et al. published the "Workshop Report: Petascale applications in biological sciences". By one measure the era of petascale computing in biology began in 2006 with the successful clocking of the Riken Institute Protein Explorer system at 1.0 PetaFLOPS. Still, the state of the art of current applications in bioinformatics and computational biology is generally yet orders of magnitude away from petascale, especially in terms of actual performance. The purpose of this is lecture is to survey the current state of the art in computational biology and bioinformatics at scale. Suggested topics for papers and posters include, but are not limited to, the following specific subjects: What is the current upper limit of scale of applications in bioinformatics and computational biology? What are the factors limiting scalability of these applications? Can we, as recommended by Snavely et al., identify candidate petascale applications in any of the following areas: biomolecular structure modeling, modeling complex biological systems, genomics, customized patient care, ecological components of earth systems modeling, infections disease modeling, or other areas? What are the best ways to measure performance scalability of bioinformatics and computational biology applications? Can we measure what really counts in terms of next generation bioinformatics applications with FLOPS and bytes? The NSF workshop organized by Snavely, Jacobs, and Bader identified several specific applications as candidates for scaling. The resulting report called for attention to progress in scaling applications by identifying problems, resolving those problems, and trying to anticipate problems at a larger scales and making the step to larger scales. Presentations that discuss the steps, challenges, and solutions to incremental scaling of bioinformatics and computational biology applications are particularly encouraged. Practice and experience papers related to this topic will be of particular value to the scientific community as we strive toward petascale applications.


This book offers an analysis of the French clitic object pronouns lui and le in the radically functional Columbia school framework, contrasting this framework with sentence-based treatments of case selection. It suggests that features of the sentence such as subject and object relations, normally taken as pretheoretical categories of observation about language, are in fact part of a theory of language which does not withstand empirical testing. It shows that the correct categories are neither those of structural case nor those of lexical case, but rather, semantic ones. Traditionally, anomalies in the selection of dative and accusative case in French, such as case government, use of the dative for possession and disadvantaging, its use in the faire-causative construction, and other puzzling distributional irregularities have been used to support the idea of an autonomous, non-functional central core of syntactic phenomena in language. The present analysis proposes semantic constants for lui and le which render all their occurrences explicable in a straightforward way. The same functional perspective informs issues of cliticity and pronominalization as well. The solution offered here emerges from an innovative instrumental view of linguistic meaning, an acknowledgment that communicative output is determined only partially and indirectly by purely linguistic input, with extralinguistic knowledge and human inference bridging the gap. This approach entails identification of the pragmatic factors influencing case selection and a reevaluation of thematic-role theory, and reveals the crucial impact of discourse on the structure as well as the functioning of grammar. One remarkable feature of the study is its extensive and varied data base. The hypothesis is buttressed by hundreds of fully contextualized examples and large-scale counts drawn from modern French texts.


Three different optical-fiber phase modulators utilizing the magnetostrictive properties of a metallic-glass alloy were constructed. By binding the optical fiber to the magnetostrictive metallic glass, the strain induced in the metallic glass that is due to the magnetic field is transferred to the optical fiber. Two ring and one flat linear modulator configurations were investigated. Each modulator's performance was evaluated by measuring the induced phase shift as a function of the excitation frequency of the magnetic field normalized by the fiber length. The highest sensitivity of 75 mrad/cm-Oe was attained for the linear modulator.


Ex vivo expansion of CD8+ T-cells has been a hindrance for the success of adoptive T cell transfer in clinic. Currently, preconditioning with chemotherapy is used to modulate the patient immunity before ACT, however, the tumor microenvironment beneficial for transferring T cells may also be damaged. Here preconditioning with single low dose of doxorubicin or paclitaxel combined with fewer CD8+ T-cells was investigated to verify whether the same therapeutic efficacy of ACT could be achieved. An E.G7/OT1 animal model that involved adoptive transfer of OVA-specific CD8+ T-cells transduced with a granzyme B promoter-driven firefly luciferase and tomato fluorescent fusion reporter gene was used to evaluate this strategy. The result showed that CD8+ T-cells were activated and sustained longer in mice pretreated with one low-dose Dox or Tax. Enhanced therapeutic efficacy was found in Dox or Tax combined with 2×106 CD8+ T-cells and achieved the same level of tumor growth inhibition as that of 5×106 CD8+ T-cells group. Notably, reduced numbers of Tregs and myeloid derived suppressor cells were shown in combination groups. By contrast, the number of tumor-infiltrating cytotoxic T lymphocytes and IL-12 were increased. The NF-κB activity and immunosuppressive factors such as TGF-β, IDO, CCL2, VEGF, CCL22, COX-2 and IL-10 were suppressed. This study demonstrates that preconditioning with single low dose Dox or Tax and combined with two fifth of the original CD8+ T-cells could improve the tumor microenvironment via suppression of NF-κB and its related immunosuppressors, and activate more CD8+ T-cells which also stay longer.


This article studies variation in conflict theater choice by Western jihadists in an effort to understand their motivations. Some militants attack at home, whereas others join insurgencies abroad, but few scholars have asked why they make these different choices. Using open-source data, I estimate recruit supply for each theater, foreign fighter return rates, and returnee impact on domestic terrorist activity. The tentative data indicate that jihadists prefer foreign fighting, but a minority attacks at home after being radicalized, most often through foreign fighting or contact with a veteran. Most foreign fighters do not return for domestic operations, but those who do return are more effective operatives than nonveterans. The findings have implications for our understanding of the motivations of jihadists, for assessments of the terrorist threat posed by foreign fighters, and for counterterrorism policy.


Abstract We examined associations between specific self-regulatory mechanisms and externalizing behavior patterns from ages 2 to 15 (N = 443). The relation between multiple self-regulatory indicators across multiple domains (i.e., physiological, attentional, emotional, and behavioral) at age 2 and at age 5 and group membership in four distinct externalizing trajectories was examined. By examining each of these self-regulatory processes in combination with one another, and therefore accounting for their shared variance, we aimed to better understand which specific self-regulatory skills were associated most strongly with externalizing behavioral patterns. Findings suggest that behavioral inhibitory control and emotion regulation are particularly important in distinguishing between children who show normative declines in externalizing behaviors across early childhood and those who demonstrate high levels through adolescence.


Graft-versus-host disease (GVHD) is a major obstacle to successful bone marrow transplantation. The role of interferon (IFN) in GVHD is currently unclear. We have previously shown that interferon (IFN) is produced in vitro by alloantigen-stimulated murine bone marrow cells. This study was initiated to examine whether IFN production occurs in vivo during GVHD. Lethally irradiated mice were given bone marrow (10(7)) and/or spleen cells (2 X 10(7)) from either allogeneic or syngeneic mice. Mice given allogeneic spleen cells or bone marrow and spleen cells showed signs of GVHD within 10 days and usually died within 20 days of transplantation. Mice undergoing GVHD were found to have significant levels of IFN activity in their sera. Serum IFN was detected early (day 3) after transplantation with optimal IFN activity (greater than or equal to 80 units) occurring at 5-6 days. The IFN activity present in the sera obtained from mice with GVHD was identified as IFN alpha/beta by using specific antisera against IFN alpha/beta and IFN gamma. In contrast, irradiated mice given T-cell-depleted allogeneic bone marrow and spleen cells failed to develop GVHD and had no detectable serum IFN activity. Irradiated mice given syngeneic bone marrow and spleen cells or only allogeneic bone marrow cells did not develop GVHD and did not produce detectable IFN activity in their sera. These results show that serum IFN activity correlates well with GVHD and opens for speculation the possibility that IFN may be involved in the pathogenesis associated with GVHD.


The goal of this work is to study human whole-body gas exchange and cerebral autoregulation using a mathematical model. Previously, a human cardiopulmonary (CP) model [45, 47] was developed, which included heart, closed-loop blood circulation, gas exchange at lungs and baroreflex control of arterial pressure. In the current study, two major extensions to the model are made. First, a description of gas exchange in the peripheral tissues is added and is coupled with the lung gas exchanger via the circulatory loop with variable transport delays. A peripheral chemosensitive loop is also added to mimic the influence of blood gas composition on the heart and vasculature. The CP model is then used to predict the integrated cardiovascular and blood-tissue gas transport responses to pronounced changes in lung gas composition, and thus simulates changes encountered in apnea with and without passive oxygenation. The second extension of the CP model includes a more detailed description of cerebral circulation, cerebrospinal fluid (CSF) dynamics, brain gas exchange and cerebral blood flow (CBF) autoregulation. Two CBF regulatory mechanisms are described: autoregulation and CO2 reactivity. Central chemoreceptor control of ventilation is also added. This new model is subsequently used to study cerebral hemodynamic and brain gas exchange responses to test protocols commonly used in the assessment of CBF autoregulation (e.g., carotid artery compression and the thigh cuff test). The model closely mimics the experimental findings and provides biophysically based insights into the dynamics and interactions of the associated physiological systems. In summary, this work represents a bold effort in large-scale modeling of physiological systems. The presented model accurately describes the physiological systems and can explain how the cardiovascular, pulmonary and autonomic nervous systems interact in response to a variety of cardiopulmonary challenges, such as apnea, carotid artery compression and the thigh cuff test. With further refinement, the model may help investigators to better understand the complex biophysics of cardiopulmonary diseases such as sleep-related disorders of breathing (obstructive and central sleep apnea) and complications associated with head-injuries.


Whilst many sanitation projects have struggled to interest their beneficiaries in the positive advantages of latrines, Zimbabwe A.H.E.A.D. projects are battling to
keep up with the demand for latrines from the communities. This paper explores a methodology that works to develop a "Culture of Cleanliness" through the establishment of Community Health Clubs. Rather than starting immediately with the implementation of a water and sanitation programme, health education is used as the first point of entry into the project area. By the end of six months of health promotion, the move to improve home hygiene comes naturally to Health Club Members, who readily contribute towards upgrading their own sanitation. In Matebeleland North Province of Zimbabwe, the technical problems of constructing latrines in collapsing Kalahari sands have made latrines expensive to construct and consequently sanitation coverage is often below 10%. To solve this problem, a technology has been devised that enables women to make interlocking bricks and line their
own pits. Whilst the main cost is below ground, the superstructure is constructed cheaply with local materials, resulting in culturally appropriate and therefore sustainable
structures. Zimbabwe A.H.E.A.D is promoting upgradeable sanitation
which sees hygiene consciousness as the most important prerequisite for safe sanitation.


Water suppliers worldwide are challenged by climate variations, but so far only the qualitative change in boundary conditions has become clear but not yet the degree and impact on the water supply systems. Short-term quality changes in surface waters can, e.g. be caused by extreme rainfalls after dry periods. Longer heat periods without rain can induce middle-term quality changes in surface waters due to lacking dilution. Furthermore, unsustainable management of groundwater can lead to long-term quality changes and to water shortages, especially in times with higher water demand. Depending on the individual situation, the expected effects on the supply system differ widely, so a general adaptation strategy will not suit the individual problems. The purpose of our work is to enable water supply companies to systematically identify potential risks resulting from climate change and other external factors in a water safety plan approach, and to adapt the supply system in a most effective way by taking advantage of ongoing modernization measures and 'no-regret'-measures. A suitable adaptation strategy should address climate change conditions as well as other external factors like changing water demand and also to take into account possible effects on every part of the supply system.


Concurrent garbage collectors are notoriously hard to design, implement, and verify. We present a framework for the automatic exploration of a space of concurrent mark-and-sweep collectors. In our framework, the designer specifies a set of "building blocks" from which algorithms can be constructed. These blocks reflect the designer's insights about the coordination between the collector and the mutator. Given a set of building blocks, our framework automatically explores a space of algorithms, using model checking with abstraction to verify algorithms in the space.
 We capture the intuition behind some common mark-and-sweep algorithms using a set of building blocks. We utilize our framework to automatically explore a space of more than 1,600,000 algorithms built from these blocks, and derive over 100 correct fine-grained algorithms with various space, synchronization, and precision tradeoffs.


In this letter, the axial distribution of Gaussian beam limited by a hard-edged aperture is studied. We theoretically analyze the axial diffraction of Gaussian beam limited by a hard-edged aperture, and give the simpler formulas of the axial diffraction intensities of Gaussian beam in Fresnel diffraction field and Fraunhofer diffraction field. The corresponding numerical calculation of axial diffraction intensity distribution of Gaussian beam with different wave waist is provided and the evolution of the diffraction distribution with the wave waist of Gaussian beam is explained. As the especial cases of the truncated Gaussian beam, the Gaussian beam in free space and the parallel light limited by the aperture are discussed too, and the system parameters of the truncated Gaussian beam which can cause it to equal to these cases are given. The theoretical results conform to the numerical analysis.


Convulsive status epilepticus is a common emergency condition in paediatric practice. Classically, it is defined as continuous or recurrent seizure activity lasting for longer than 30 min in which the patient does not regain baseline mental status.1 Commonly, intervention is recommended after only 5 min of seizure activity2 as neuronal damage may begin to occur after this period, and the longer a seizure continues, the less likely it is to stop spontaneously.3 It seems likely, however, that mortality and morbidity after prolonged seizures should often be dependent upon underlying aetiology rather than duration of seizure activity.4 Repetitive serial seizures (ie, seizure clusters with return to baseline between events, but occurring frequently enough to be highly disruptive) and non-convulsive status epilepticus are also relatively common in children with epilepsy and are associated with significant morbidity.5

Diazepam, lorazepam and midazolam, the drugs most widely used to stop prolonged seizures, are members of the benzodiazepine family, a class of psychoactive drugs with varying hypnotic, sedative, anxiolytic, anticonvulsant, muscle relaxant and amnesic properties.6 Differences in their affinity for receptor subtypes account for different pharmacological effects, in combination with widely varying pharmacokinetic profiles. These pharmacokinetic differences often impose specific routes of administration and specific formulations for individual members of the benzodiazepine family. The aim of this review is to detail their clinical pharmacology as it relates to their use in the management of prolonged seizures in children.

Benzodiazepines produce their range of effects by modulation of the γ-aminobutyric acid receptor subtype A (GABAA). The GABAA receptor comprises five subunits; each receptor is assembled from a combination of polypeptides, most commonly two αs, two βs and one γ, although several other subunits exist (eg, δ, e, π, θ and ρ).7 The combination of different subunits governs the …


Communalism has been a dominating factor of 'secular' India especially post-Partition and is often accompanied by deeply rooted religious prejudices resulting in vengeance and hatred. The communal violence at various times in the past half-a-century brings forward the barbarity exhibited in the name of religion. These incidents have captured the imagination of several filmmakers from time to time. One such film is Firaaq, which sheds light on the various contoursof Gujarat violence. The present paper analyses the women characters of the film to reveal the implications of communal disturbances on them and facilitate a discourse on the associated multi-layered ramifications. The focus is on how communal rampages shape or alter the experiences of women owing to their varied religions and class positions in the society.


Neural selectivity to orientation is one of the simplest and most thoroughly-studied cortical sensory features. Here, we show that a large body of research that purported to measure orientation tuning may have in fact been inadvertently measuring sensitivity to second-order changes in luminance, a phenomenon we term 'vignetting'. Using a computational model of neural responses in primary visual cortex (V1), we demonstrate the impact of vignetting on simulated V1 responses. We then used the model to generate a set of predictions, which we confirmed with functional MRI experiments in human observers. Our results demonstrate that stimulus vignetting can wholly determine the orientation selectivity of responses in visual cortex measured at a macroscopic scale, and suggest a reinterpretation of a well-established literature on orientation processing in visual cortex.


ABSTRACT The current study examines the contributions of family context (e.g. life events, home environments) to low-income preschool children's self-regulation (behaviour regulation and executive function) in the United States and Turkey. Participants were 1139 low-income children (486 from the U.S. and 653 from Turkey) and their parents. Children's self-regulation was assessed via structured tasks and family related variables such as life events, home environments, and demographic information were assessed via parent-report. Results from regression analyses showed that child's age-predicted behaviour regulation and executive function in children both from the U.S. and Turkey. Child gender, favouring girls predicted behaviour regulation and executive function and parent–child verbal interaction was associated with behaviour regulation only in the U.S. Family structure (favouring living in a two-parent household) predicted executive function and economic change predicted behaviour regulation in Turkey. Contributions and future directions were also discussed.


The post-exercise recovery consists in restoring the body systems to baseline condition, providing balance and preventing injuries installation and, in that sense; it becomes an important aspect of every fitness program, at any levels of performance, but especially in higher levels. The objective of this review was to gather information and to describe the responses provided by post-exercise recovery methods, such as cryotherapy, contrast water immersion, massage and active recovery, providing an update on this issue. MedLine, Scielo and Lilacs databases were used, as well as the SportsDiscus list of journals. Only randomized controlled and non-controlled clinical essays, in addition to review articles concerning the proposed topic were included. Our choice was for the search terms: cryotherapy, massage, active recovery, thermotherapy, immersion and exercise, individually and combined. It was observed that some studies report that cryotherapy is harmful concerning post-exercise recovery, once it reduces performance immediately after the technique application. On the other hand, studies point it as being beneficial due to its reduction in the creatine kinase level after exercise, avoiding hence muscle damage. Concerning contrast water immersion, although it presents significance when it comes to blood lactate removal, its effectiveness needs to be better discussed. Regarding massage and active recovery, the main described biases relate to the pressure and intensity of the exercise, respectively. Among the techniques, contrast water immersion and active recovery seem to have similar effects concerning lactate removal and creatine kinase decrease. It is highlighted that the exposure time is crucial for all methods. However, several studies do not try to identify the real physiological effects promoted by the techniques, having them in limited use. Therefore, the inconsistency of the results found suggests that the assessed variables used as a recovery method should be better controlled.


This article provides answers to the two questions posed in the title. It is argued that, contrary to many statements made in the literature, neither entropy, nor the Second Law may be used for the entire universe. The origin of this misuse of entropy and the second law may be traced back to Clausius himself. More resent (erroneous) justification is also discussed.


A great deal of attention has been devoted to risk research. Sociologists in general have limited themselves to varying recognitions of a society at risk and have traced out the paths to disaster. The detailed research has yet to be undertaken. In Risk, now available in paperback, Niklas Luhmann develops a theoretical program for such research. His premise is that the concept of risk projects essential aspects of our description of the future onto the present. Risk is conceived as the possibility of triggering unexpected, unlikely, and detrimental consequences by means of a decision attributable to a decision maker.


US experts in infection control are reviewing advice issued in 2002 that intravenous devices should be replaced every 72 to 96 hours as a matter of routine.

Updated guidance from the Centers for Disease Control infection control advisory group (HICPAC) is expected to be published this winter. A draft says that peripheral intravenous devices should be replaced "no more frequently than every 72-96 hours" but that evidence for leaving catheters in place unless clinically indicated was an "unresolved issue."

The 2002 guidelines are based on findings from early small studies that suggested routine replacement might limit complications such as phlebitis. But the proposed change comes as evidence mounts that replacing intravenous devices every three days is not clinically indicated. A Cochrane review published earlier …


This paper presents a comparative eigenvalue analysis of the stability characteristics and small signal dynamics of four different control strategies for Synchronous Machine Emulation (SME) by power electronic converters, considering a Synchronous Machine (SM) as the benchmark system. The four SME techniques are selected to represent the most established general approaches for emulating the inertial characteristics of SMs in the control of power electronic converters. The small-signal stability assessment is based on the analysis of system eigenvalues, including evaluation of participation factors and parametric sensitivities. All the investigated techniques can be tuned to obtain similar inertial dynamics under grid frequency variations, but exhibit differences in other small-signal characteristics due to the distinct control system implementations. Among the analyzed cases, the current-controlled virtual synchronous machine has the highest damping of the most oscillatory mode. However, the study shows that the most oscillatory modes of the other techniques are associated with the LCL impedance, and could be further attenuated by active damping techniques.


Introduction Achilles tendinopathy is a common problem among athletes (Jarvinen, Kannus et al. 2005). Various risk factors exist and poor endurance is likely to be one of these (Silbernagel, Gustavsson et al. 2006, Malliaras, Barton et al. 2013). Eccentric training is an effective treatment for Achilles tendinopathy(Alfredson, Pietila et al. 1998). This study was designed to investigate the potential effect of eccentric training on endurance of the triceps surae muscles to indicate whether endurance could be improved in healthy individuals and to establish whether eccentrics may have a potential role within primary prevention of Achilles tendinopathy. The reliability of endurance measured using isokinetic dynamometry was assessed. Methods 37 volunteers (29 males, 8 females) took part in the reliability study and 32 volunteers (24 males, 8 females) in the effect of eccentrics on endurance study. Subjects were tested using the Cybex Humac Norm© isokinetic dynamometer under controlled conditions, on two occasions (2–7 days apart). The endurance test on both legs was 20 repetitions long, at a velocity of 90°S-1, in both eccentric and concentric movements in bent knee (90°) and straight leg positions. 32 subjects were re-tested after 12 weeks of eccentric training on one leg (with the other leg used as a control). Results Results showed that Total Work Done was a reliable measure of endurance (ICC range 0.75–0.91) but that Fatigue Index and Endurance Ratio were not (ICC range -0.44–0.67). Significant improvements in bent knee (see figure 1) and straight leg positions in concentric; trained and non-trained legs and in eccentric; trained leg only were observed in the low baseline endurance group. Only concentric; trained leg in the bent knee position significantly improved in the high baseline endurance group suggesting that eccentric training has the capacity to improve endurance in those with underlying deficits. Abstract 49 Figure 1 Bent knee There is a statistically significant improvement in all results in Total Work Done over the 12 week period in participants with a low baseline endurance level. The whiskers represent the ranges of all values, the box represents the quartiles above and below the median, the line within the box indicates the median Total Work Done, 'pre' represents results before eccentric training and 'post' represents results after Discussion This study has identified a reliable isokinetic measure for endurance of the calf muscles and a method for improving calf muscle endurance. Investigation of the potential application of eccentric training as prevention of Achilles tendinopathy requires further research. References Alfredson, H. et al. Am J Sport Med. 1998;26(3):360–366 Jarvinen, TA. et al. Foot Ankle Clin. 2005;10(2):255–266 Malliaras, P. et al. Sports Medicine (Auckland, N. Z.), 43(4):267–286 Silbernagel, KG. et al . Knee surgery, sports traumatology, arthroscopy: official journal of the ESSKA, 14(11):1207–1217


Nature and quality of "cities", in general, and "Islamic cities", in particular, in religious schools are the origin of some broad topics. Therefore, by resorting to religious texts on the one hand and a more comprehensive understanding of the fundamentals of historical cities on the other hand, we can define new horizons within the framework of Islamic-Iranian cities. Targeted development and future image of a city will be only possible if an understanding of the quality of the future city is clarified. Strategies are several ways to achieve goals and visions of a city, among which the best ones should be selected and taken as core strategies of the plan. to achieve goals and visions of a city, the designated strategies should be executed. In other words, it should be clearly specified in the plan of urban development strategy that which person or organization will conduct the project and with which kinds of resources. The aim of this study is to develop a strategic planning framework for the IslamicIranian cities. The present article is an inter-religious study; its strategy is interpretive. The method is based on the accuracy of the contents and tips of religious texts using the method of content analysis. Its strategic approach is based on heuristic approach. The results of this research include the development of Islamic values in Iranian cities through some theoretical bases; visions and missions of the study involve a statement on the values of IslamicIranian cities. Regarding to the value statement and the strategic planning process, the main and the consequential objectives of realization of the IslamicIranian cities are to be proposed.


We investigate the consolidation of two optical networks, which overlap in some geographical areas, by installing interconnection links at strategic locations to reduce system operational costs. We focus on the operational costs of fiber links in the networks. The minimum number of operational fiber links required to provide bi-directional connectivity for any two nodes of the merged network is examined. Analytical results show that it is at least the number of nodes or at least twice the number of bridges when all the co-located nodes are interconnected. The optimal locations of interconnection links are derived when the interconnection cost is very high, which results in a minimum of two interconnections. They should be installed at the nodes which are one hop away from two certain cut nodes if there are cut nodes in the networks. To take into account more practical considerations, single link failure protection schemes for the merged network are also studied.


Industry veteran Raymond Nickerson provides an extensive introduction to the information technology revolution that is transforming industrial society. He focuses particularly on the study of person-computer interaction, noting how computers are affecting their users and society as a whole, and describes a variety of ways in which information technology is expected to develop in the forseeable future.Nickerson summarizes the development of information technology and discusses many of its applications - in farming, research, education and training, manufacturing, general management, retailing, defense, and elsewhere - that have already had a substantial impact on society. He reviews the human-factors research that has been done and is underway, with special attention to the physical and cognitive interface, including languages, conversational interactions, and the concepts of friendliness and usability.Raymond S. Nickerson is Senior Vice President of BBN Laboratories, a subsidiary of Bolt Beranek and Newman Inc. A Bradford Book.


Microbial colonisation is paramount to the normal development of the immune system, particularly at mucosal sites. However, the relationships between the microbiome and the adaptive immune repertoire have mostly been explored in rodents and humans. Here, we report a high-throughput sequencing analysis of the chicken TCRβ repertoire and the influences of microbial colonisation on tissue-resident TCRβ+ cells. The results reveal that the microbiome is an important driver of TCRβ diversity in both intestinal tissues and the bursa of Fabricius, but not in the spleen. Of note, public TCRβ sequences (shared across individuals) make a substantial contribution to the repertoire. Additionally, different tissues exhibit biases in terms of their V family and J gene usage, and these effects were influenced by the gut-associated microbiome. TCRβ clonal expansions were identified in both colonised and germ-free birds, but differences between the groups were indicative of an influence of the microbiota. Together, these findings provide an insight into the avian adaptive immune system and the influence of the microbiota on the TCRβ repertoire.


This new title in the renowned Art & Ideas series is a thorough introduction to, and significant appraisal of, the art of Pop. Bradford Collins explains the essence of Pop art and examines its full history in contemporary cultural and political context - the origins of the movement during the 1950s, the flourishing of Pop art in America and the UK during the 1960s, and its further incarnations and more widespread impact. The 250 illustrations include all the most classic examples of Pop art by such well-known figures as Andy Warhol and Roy Lichtenstein, as well as lesser known works that have been neglected in recent years but are essential to a thorough understanding of Pop. Contemporary source material used by artists to make their works and consideration of what was in the media at the time support discussions of the inspiration, creation and impact of the art.


This article evaluates the cost and crime‐reducing potential of prisons and social spending, setting forth the conditions under which a shift in resources from an expanding prison population into social spending would lead to a reduction in total crime. Preschool enrichment programs coupled with family intervention have generated impressive results in reducing crime in a number of different studies. Targeting of resources toward those children most at risk of criminal behavior is necessary to generate cost‐effective crime reduction, but this may be difficult to achieve because of political or constitutional constraints. Given precise targeting, and if a broadly implemented preschool program (more enriched than the current Head Start program) could generate half the crime‐reduction benefits achieved in the pilot studies, then cutting spending on prisons and using the savings to fund intensive preschool education would reduce crime. The elasticity of crime with respect to incarceration is taken to be .15.


ABSTRACT Introduction: The complexity of the endocannabinoid (eCB) system is becoming better understood and new drivers of eCB signaling are emerging. Modulation of the activities of the eCB system can be therapeutic in a number of diseases. Research into the eCB system has been paralleled by the development of agents that interact with cannabinoid receptors. In this regard it should be remembered that herbal cannabis contains a myriad of active ingredients, and the individual cannabinoids have quite distinct biological activities requiring independent studies. Areas covered: This article reviews the most important current data involving the eCB system in relation to human diseases, to reflect the present (based mainly on the most used prescription cannabinoid medicine, THC/CBD oromucosal spray) and potential future uses of cannabinoid-based therapy. Expert commentary: From the different therapeutic possibilities, THC/CBD oromucosal spray has been in clinical use for approximately five years in numerous countries world-wide for the management of multiple sclerosis (MS)-related moderate to severe resistant spasticity. Clinical trials have confirmed its efficacy and tolerability. Other diseases in which different cannabinoids are currently being investigated include various pain states, Alzheimer's disease, Parkinson's disease, Huntington's disease and epilepsy. The continued characterization of individual cannabinoids in different diseases remains important.


Women are left out in Nkhoma Synod in that they are not allowed to be in leadership position, as church ministers, following the biblical patriarchy. Secondly, women are not offered theological trainings. The purpose of this case study is to critically evaluate the role of women in the church today. This paper gives a background of CCAP Malawi and Nkhoma Synod and how women have been viewed since the introduction of Christianity in the central region of Malawi. In addition, how this in turn has contributed to the development of the congregations and the Synod as a whole. This study also reveals how Christianity influenced culture and traditions in society of Malawi's Central Region. Women represent 65% of the Church membership. Best tools helps one to have a good result, in this case study, gender and power, and ecumenical diakonia theories were used to help answer the research question. Observations and interviews were done with influential leaders and ministers of congregation, women in the leadership positions and in laity. Secondly, published and unpublished sources have been used together with internet sources. The paper has analyzed and explored the need for Nkhoma Synod to address gender and power issues, being a Church and a diaconal actor. The paper suggests the need to transform and empower the women in all areas of the church existence.


This paper presents the first 4Kp30 end-to-end video streaming demonstration based on the upcoming Scalable High efficiency Video Coding (SHVC) standard. The optimized and parallel SHVC decoder is used under the GPAC player to decode and display in real time the received SHVC layers. The SHVC reference software model (SHM) is used to encode the 4K original video in two spatial scalability layers: the base layer at 1080p resolution and the enhancement layer at 2160p resolution. The SHVC bitstream is encapsulated with the GPAC multimedia library into MP4 file format. The GPAC player at the server side broadcasts the MP4 content in MPEG-2 TS. At the client side, the GPAC player receives the SHVC video packets which are decoded by the SHVC decoder and then rendered in real time by the player. The GPAC player provides an interactive interface enabling to switch between displaying the base and the enhancement layers.


OBJECTIVE Cannabidiol (CBD) and Δ9-tetrahydrocannabivarin (THCV) are nonpsychoactive phytocannabinoids affecting lipid and glucose metabolism in animal models. This study set out to examine the effects of these compounds in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS In this randomized, double-blind, placebo-controlled study, 62 subjects with noninsulin-treated type 2 diabetes were randomized to five treatment arms: CBD (100 mg twice daily), THCV (5 mg twice daily), 1:1 ratio of CBD and THCV (5 mg/5 mg, twice daily), 20:1 ratio of CBD and THCV (100 mg/5 mg, twice daily), or matched placebo for 13 weeks. The primary end point was a change in HDL-cholesterol concentrations from baseline. Secondary/tertiary end points included changes in glycemic control, lipid profile, insulin sensitivity, body weight, liver triglyceride content, adipose tissue distribution, appetite, markers of inflammation, markers of vascular function, gut hormones, circulating endocannabinoids, and adipokine concentrations. Safety and tolerability end points were also evaluated. RESULTS Compared with placebo, THCV significantly decreased fasting plasma glucose (estimated treatment difference [ETD] = −1.2 mmol/L; P < 0.05) and improved pancreatic β-cell function (HOMA2 β-cell function [ETD = −44.51 points; P < 0.01]), adiponectin (ETD = −5.9 × 106 pg/mL; P < 0.01), and apolipoprotein A (ETD = −6.02 μmol/L; P < 0.05), although plasma HDL was unaffected. Compared with baseline (but not placebo), CBD decreased resistin (−898 pg/ml; P < 0.05) and increased glucose-dependent insulinotropic peptide (21.9 pg/ml; P < 0.05). None of the combination treatments had a significant impact on end points. CBD and THCV were well tolerated. CONCLUSIONS THCV could represent a new therapeutic agent in glycemic control in subjects with type 2 diabetes.


We used airborne light detection and ranging (LiDAR) data to reevaluate the single-event offsets of the 1920 Haiyuan Ms 8.5 earthquake and the cumulative offsets along the western and middle segments of the coseismic surface rupture zone. Our LiDAR data indicate that the offset observations along both the western and middle segments fall into groups. The group with the minimum slip amount is associated with the 1920 Haiyuan Ms 8.5 earthquake, which ruptured both the western and middle segments. Our research highlights two new interpretations: First, the previously reported maximum displacement of the 1920 earthquake was likely due to at least two earthquakes; second, our results reveal that the cumulative offset probability density (COPD) peaks of the same offset amounts on the western and middle segments do not correspond to one another one-to-one. We suggest that any discussion of the rupture pattern of a certain fault based on the offset data should also consider fault segmentation and paleoseismological data. Therefore, the COPD peaks should be computed and analyzed on fault subsections and not entire fault zones to study the number of paleoearthquakes and their rupture patterns.


JNK3 promotes the generation of β-amyloid and ER stress in Alzheimer's disease. In Alzheimer's disease, processing of the transmembrane amyloid precursor protein (APP) generates soluble β-amyloid (Aβ) peptides, such as Aβ42, that oligomerize, aggregate, and form plaques in the brain, resulting in neurodegeneration. Yoon et al. investigated the role of c-Jun N-terminal kinase (JNK) activation by the endoplasmic reticulum (ER) stress response, which is activated in brain from patients who died of Alzheimer's disease. Blocking protein translation triggers ER stress and can be induced by activation of the kinase AMPK, which inhibits mTOR signaling by phosphorylating TSC2 at Ser3187 to activate TSC2 and by phosphorylating Raptor at Ser792 to inhibit Raptor. Treatment of cultured rat hippocampal neurons with Aβ42 induced a translational block and was associated with increased activation of AMPK (as indicated by phosphorylation of Thr172) and increased phosphorylation of Ser3187 in TSC2 and of Ser792 in Raptor. JNK3 phosphorylated Thr668 in APP in vitro. The authors hypothesized that this phosphorylation event would promote amyloidogenic processing of cell surface APP by triggering its endocytosis. Activation of JNK with anisomycin initially increased, then decreased, the amount of cell surface APP, an effect that required phosphorylation of Thr668 and was inhibited by the concurrent application of peptides derived from JNK-interacting protein (JIP) to inhibit JNK. Furthermore, anisomycin treatment increased the processing of APP, which required phosphorylation of Thr668. Kinase assays indicated that JNK3 activity was higher in Alzheimer's disease patients than in normal cases and in FAD mice, which are a model for Alzheimer's disease, than in control mice. Immunohistochemistry with a pan-JNK antibody detected phosphorylated and activated JNK near plaques in FAD mice with JNK3 (FAD:JNK3+/+) but not in FAD mice lacking JNK3 (FAD:JNK3–/–), indicating that JNK3 is the primary JNK isoform that is activated in FAD mice. Deletion of JNK3 in FAD mice resulted in decreased Aβ42 abundance, diminished phosphorylation of Thr668 in APP, reductions in the number and size of plaques, and improved cognition (as indicated by increased long-term retention of fear memories) compared with FAD:JNK3+/+ mice. Phosphorylation of the ribosomal protein S6 at Ser235 and Ser236, a marker for active translation, was increased in FAD:JNK3–/– mice; whereas phosphorylation of Raptor at Ser792 was increased in FAD:JNK3+/+ mice, suggesting a block in global translation in FAD:JNK3+/+ mice. Western blot analysis indicated increased ER stress in FAD:JNK3+/+ compared with FAD:JNK3–/– mice and in cortical samples from Alzheimer's disease patients compared with control cases. Thus, targeting JNK3 in Alzheimer's disease could reduce the processing of APP into oligomeric Aβ peptides and the ER stress caused by Aβ peptides. S. O. Yoon, D. J. Park, J. C. Ryu, H. G. Ozer, C. Tep, Y. J. Shin, T. H. Lim, L. Pastorino, A. J. Kunwar, J. C. Walton, A. H. Nagahara, K. P. Lu, R. J. Nelson, M. H. Tuszynski, K. Huang, JNK3 perpetuates metabolic stress induced by Aβ peptides. Neuron 75, 824–837 (2012). [Online Journal]


In the present study, we summarize and evaluate the endeavors from recent years to estimate the maximum possible earthquake magnitude mmax from observed data. In particular, we use basic and physically motivated assumptions to identify best cases and worst cases in terms of lowest and highest degree of uncertainty of mmax. In a general framework, we demonstrate that earthquake data and earthquake proxy data recorded in a fault zone provide almost no information about mmax unless reliable and homogeneous data of a long time interval, including several earthquakes with magnitude close to mmax, are available. Even if detailed earthquake information from some centuries including historic and paleoearthquakes are given, only very few, namely the largest events, will contribute at all to the estimation of mmax, and this results in unacceptably high uncertainties. As a consequence, estimators of mmax in a fault zone, which are based solely on earthquake‐related information from this region, have to be dismissed.


The architectural, engineering and construction industry (AEC Industry) needs to focus on the early design phases. The use of Lean Design Management and Building Information Model (BIM) can be used together for reducing uncertainty and improve communication. BIM requires new working methods, and the use of Level of Development (LoD) or model maturity is proposed as a key element to align the challenges in the design phase and to generate an enhanced design process. This paper addresses these challenges and aim to answer three research questions. RQ1: What approaches to model maturity are used or attempted in the Norwegian AEC industry? RQ2: What experiences do the actors of the AEC industry have towards the use of model maturity? RQ3: How can model maturity be implemented in an AEC project? The research method is based on a literature study and a study based on semi–structured interviews. This paper presents an analysis of the interviewees regarding the experiences the industry has with the use of model maturity. There is proposed a framework based on the results, about how to implement model maturity in construction projects. The framework is generic and can be adapted to different construction projects independent of contract form.


We present a practice-based research project, which examines temporal relationships between physiological processes with human movement and mediated environments. Ongoing research will provide a foundation for the creation of performances in which real-time heart rate data from contemporary dancers is used to generate click tracks for live musicians. The complex constructions of time in this project necessitate novel visualization strategies throughout the research, development, creation, and production process, including: time domain display of data with rich and facile interaction using bokeh; visualization of biometric data as a form of biofeedback; and unique representations of time in music notation.


Participatory and deliberative democrats are increasingly relying on groups of "lay" citizens to have a direct hand in policy formation and consultation. However, these theorists have not adequately addressed how these "citizen representatives" should be selected and how their activities can be truly deemed "representative". We find these lacunae unsurprising in light of continued confusion in the representation literature about the relationship between democracy and representation - and the continued lack of effort to bridge normative theories of political representation with sensitivity to real institutional practices of representation. Accordingly, we look at a particular institutional manifestation of democratic representation - the American jury system - and tease out a theory of "citizen representation" that highlights six central desiderata: deliberation, impartiality, cross-sectionality, civic responsibility, legitimacy, and indirect accountability. An analogy that proves rich upon examination, we find that the jury's implicit theory of citizen representation has much to recommend to proposals and practices of citizen representation in other institutional settings.


This book is a detailed study of French-English linguistic borrowing in Prince Edward Island, Canada which argues for the centrality of lexical innovation to grammatical change. Chapters 1–4 present the theoretical and methodological perspectives adopted along with the sociolinguistic history of Acadian French. Chapter 5 outlines the basic features of Acadian French morphosyntax. Chapter 6 provides an overview of the linguistic consequences of language contact in Prince Edward Island. Chapters 7–9 consider three particular cases of grammatical borrowing: the borrowing of the English adverb back and the semantic and syntactic reanalysis it has undergone, the borrowing of a wide range of English prepositions, resulting in dramatic changes in the syntactic behaviour of French prepositions, and the borrowing of English wh-ever words, resulting in the emergence of a new type of free relative. Chapter 10 argues for a theory of grammar contact by which contact-induced grammatical change is mediated by the lexicon.


Converging evidence suggests that representations of number, space, and other dimensions depend on a general representation of magnitude. However, it is unclear whether there exists a privileged relation between certain magnitude dimensions or if all continuous magnitudes are equivalently related. Four-year-old children and adults were tested with three magnitude comparison tasks – nonsymbolic number, line length, and luminance – to determine whether individual differences in sensitivity are stable across dimensions. A Weber fraction (w) was calculated for each participant in each stimulus dimension. For both children and adults, accuracy and w values for number and line length comparison were significantly correlated, whereas neither accuracy nor w was correlated for number and luminance comparison. However, although line length and luminance comparison performance were not correlated in children, there was a significant relation in adults. These results suggest that there is a privileged relation between number and line length that emerges early in development and that relations between other magnitude dimensions may be later constructed over the course of development.


Classifiers based on statistical pattern recognition analysis of MRSI data are becoming important tools for the non-invasive diagnosis of human brain tumors. Here we investigate the potential interest of perturbation-enhanced MRSI (PE-MRSI), in this case acute hyperglycemia, for improving the discrimination between mouse brain MRS patterns of glioblastoma multiforme (GBM), oligodendroglioma (ODG), and non-tumor brain parenchyma (NT). Six GBM-bearing mice and three ODG-bearing mice were scanned at 7 Tesla by PRESS-MRSI with 12 and 136 ms echo-time, during euglycemia (Eug) and also during induced acute hyperglycemia (Hyp), generating altogether four datasets per animal (echo time + glycemic condition): 12Eug, 136Eug, 12Hyp, and 136Hyp. For classifier development all spectral vectors (spv) selected from the MRSI matrix were unit length normalized (UL2) and used either as a training set (76 GBM spv, four mice; 70 ODG spv, two mice; 54 NT spv) or as an independent testing set (61 GBM spv, two mice; 31 ODG, one mouse; 23 NT spv). All Fisher's LDA classifiers obtained were evaluated as far as their descriptive performance-correctly classified cases of the training set (bootstrapping)-and predictive accuracy-balanced error rate of independent testing set classification. MRSI-based classifiers at 12Hyp were consistently more efficient in separating GBM, ODG, and NT regions, with overall accuracies always >80% and up to 95-96%; remaining classifiers were within the 48-85% range. This was also confirmed by user-independent selection of training and testing sets, using leave-one-out (LOO). This highlights the potential interest of perturbation-enhanced MRSI protocols for improving the non-invasive characterization of preclinical brain tumors.


Policy decisions about the UK railway industry often draw on models and frameworks that treat technology and organisational processes as static and unchanging. As a result, policy makers often have limited understanding of how changes in policy will influence organisational knowledge, learning and the allocation of risk that subsequently affects innovation and system development. This paper applies a business model lens, focused on the mechanisms firms use to create and capture value, to connect policy decisions to subsequent changes in the organisation and industrial structure of the UK railway sector. By analysing innovation-related activity across several different governance structures, the paper highlights how policy impacts in network-based infrastructure sectors are mediated by business strategy, sometimes leading to unintended outcomes. The findings suggest that policy to improve the performance should focus upon coordination rather than just ownership. The application of a business model approach...


The disturbance observer (DOB) is a tool for the robust motion control and it is used to compensate the disturbances. In the design of the DOB, it is assumed that, the system disturbance is observed and compensated by the DOB in the range of its bandwidth. However, the whole bandwidth cannot be compensated by the DOB due to the dynamical characteristics of the disturbance observer's low pass filter (LPF). Higher Order Disturbance Observer (HODOB) is one of the fundamental tools to increase the performance of the DOB, even though it has some disadvantages. However, the performance analysis of HODOB has not been clearly reported yet. In this paper, analysis and design methods of the HODOB are presented by using a more general disturbance model. This general model gives more freedoms to design HODOB. Also the superiors of the position measurement based HODOB design are shown. Simulation and experimental results are given to show the validity of the proposed methods.


Prior to the application of any persistent scatterer interferometry (PSI) technique for the monitoring of terrain displacement phenomena, an adequate pixel selection must be carried out in order to prevent the inclusion of noisy pixels in the processing. The rationale is to detect the so-called persistent scatterers, which are characterized by preserving their phase quality along the multi-temporal set of synthetic aperture radar (SAR) images available. Two criteria are mainly available for the estimation of pixels' phase quality, i.e., the coherence stability and the amplitude dispersion or permanent scatterers (PS) approach. The coherence stability method allows an accurate estimation of the phase statistics, even when a reduced number of SAR acquisitions is available. Unfortunately, it requires the multi-looking of data during the coherence estimation, leading to a spatial resolution loss in the final results. In contrast, the PS approach works at full-resolution, but it demands a larger number of SAR images to be reliable, typically more than 20. There is hence a clear limitation when a full-resolution PSI processing is to be carried out and the number of acquisitions available is small. In this context, a novel pixel selection method based on exploiting the spectral properties of point-like scatterers, referred to as temporal sublook coherence (TSC), has been recently proposed. This paper seeks to demonstrate the advantages of employing PSI techniques by means of TSC on both orbital and ground-based SAR (GB-SAR) data when the number of images available is small (10 images in the work presented). The displacement maps retrieved through the proposed technique are compared, in terms of pixel density and phase quality, with traditional criteria. Two X-band datasets composed of 10 sliding spotlight TerraSAR-X images and 10 GB-SAR images, respectively, over the landslide of El Forn de Canillo (Andorran Pyrenees), are employed for this study. For both datasets, the TSC technique has showed an excellent performance compared with traditional techniques, achieving up to a four-fold increase in the number of persistent scatters detected, compared with the coherence stability approach, and a similar density compared with the PS approach, but free of outliers.


Objective: The aim of this study is to evaluate the response to shock wave therapy in a group of patients with vasculogenic erectile dysfunction after underwent deep dorsal vein embolization. Methods: A clinical record of 30 patients from 26 to 45 years with a clinical diagnosis of vasculogenic ED of more than six months and without venous leakage from legs of the penis, and cancer pathology has not been identified. Patient diagnostics consisted of questionnaire (IIEF-5), Penile Pharmacological Doppler Ultrasonography and CT Cavernosography. After confirming the diagnosis of vasculogenic ED, they all underwent deep dorsal vein embolization. Then the second stage all patients received a treatment by the shockwave device "BTL-6000 SWT TOPLINE" (BTL Corporate). The effectiveness of therapy was evaluated by two criteria: the IIEF-5 score and evaluation of penile blood flow. Results: The average IIEF-5 score has greatly increased from 16.7 at baseline to 22.2 post treatment. Out of 30 patients, 26 (81%) subjectively noted a persistent improvement in erectile function. An increase in the penile blood flow in the right cavernosum artery from 17.7 mm Hg at baseline to 34 mm Hg post treatment, in the left cavernosum artery from 13.2 mm Hg to 28.3 mm Hg, in the right dorsal artery from 18 mm Hg to 32 mm Hg and in the left dorsal artery from 16 mm Hg to 33 mm Hg. As well as, increase in the diameter of the cavernous bodies was noted. Conclusion: The results of this study indicate erectile dysfunction treatment should have a personalized approach. Shock wave therapy in combination with the reduction of venous outflow may be an alternative to revascularization of the penis.


Pit lakes may form in mining voids that extend below groundwater level after mining ceases and many have been found to have elevated metals concentrations and low pH through acidic and metalliferous drainage (AMD). Pit lakes are often used for recreational activities including swimming, fishing and boating and poor water quality may present health risks to recreational users. Pit lakes also provide the opportunity for additional water resource uses. The Collie Coal Basin in south-western Australia currently has a number of pit lakes with moderate AMD effects which are also used for recreational pursuits. Twelve hundred questionnaires were mailed to selected addresses in the Collie shire with an additional 170 questionnaires to specific interest groups. Participants were asked about the type of activity, frequency and duration and any health symptoms experienced after use of the lakes. Two hundred and fifty questionnaires were returned, which comprised 176 returns from the random sample and 74 from the targeted sample. Three pit lakes with elevated metals concentrations and low pH were used for recreational purposes by 62% of respondents. This was mostly in summer with swimming the most common activity. Of all respondents 52% were concerned about lake water quality and 38% using the lakes reported a variety of symptoms. Recreational use of Collie pit lakes did not represent a health risk for most of the surveyed population due to the low frequency and duration of use, however health risks may be elevated in sensitive users such as children and those consuming seafood from the lakes. Comprehensive water quality monitoring for chemicals and further characterisation of recreational use of pit lakes is warranted to more comprehensively assess the potential health risks to recreational users. Post closure mine plans need to consider potential future community uses combined with assessments of water quality and physical characteristics to reduce the potential for adverse health and safety impacts.


Electrical stimulation in the periaqueductal gray (PAG) can inhibit dorsal horn cell responses to both innocuous and noxious cutaneous stimuli. This inhibition is believed to be due to the release of serotonin (5-HT) into the dorsal horn of the spinal cord from descending axons of the nucleus raphe magnus and the adjacent reticular formation. It is still not clearly known which subtypes of 5-HT receptors are involved in the PAG-induced inhibition. Extracellular single-unit recordings of dorsal horn cell activity, in combination with drug administration through a microdialysis fiber, were used to test the role of 5-HT3 receptors in PAG-induced inhibition. The responses of the cells to mechanical stimulation of the skin (BRUSH, PRESS and PINCH) and to the same stimuli while stimulating PAG were recorded. When the 5-HT3 antagonist, ondansetron, was perfused through the microdialysis fiber, not only was the background activity of the cell increased, but also the responses to BRUSH, PRESS and PINCH stimuli. The PAG-induced inhibition of responses to the same stimuli was partially or completely blocked by ondansetron. Another 5-HT3 antagonist, zacopride, did not increase the background activity or responses to PRESS and PINCH, yet this agent, like ondansetron, blocked PAG inhibition. The 5-HT3 agonist, phenylbiguanide, inhibited the background activity and the responses to mechanical stimuli. These results suggest that 5-HT released in the dorsal horn by stimulation in the PAG excites inhibitory interneurons through 5-HT3 receptors, resulting in inhibition of dorsal horn neurons.


Seven Albian sea-level curves from localities around the globe have been correlated on the basis of the number and timing of transgressive-regressive cycles shown. The localities chosen were considered to have been tectonically stable. There are 11 time lines placed in the different sections by use of graphic correlation. They are based on the position of European ammonite zonal-subzonal boundaries projected into sections in North America and the Middle East. The examined sea-level sequences (with durations of 0.3–2.7 m.y.) appear to vary regionally, and their global correlation cannot be demonstrated with the present stratigraphic resolution. Frequency trends show that Albian sea level was statistically stable from the late early to the early late Albian, whereas it fluctuated rapidly in earliest and latest Albian.


Objective. To get a better understanding of inflammatory pathways active in the osteoarthritic (OA) joint, we characterized and compared inflammatory cells in the synovium and the infrapatellar fat pad (IFP) of patients with knee OA. Methods. Infiltrating immune cells were characterized by flow cytometry in 76 patients with knee OA (mean age 63.3, 52% women, median body mass index 28.9) from whom synovial tissue (n = 40) and IFP (n = 68) samples were obtained. Pain was assessed by the visual analog scale (VAS; 0–100 mm). Spearman rank correlations and linear regression analyses adjusted for sex and age were performed. Results. Macrophages and T cells, followed by mast cells, were the most predominant immune cells in the synovium and IFP, and were equally abundant in these tissues. Macrophages and T cells secreted mostly proinflammatory cytokines even without additional stimulation, indicating their activated state. Accordingly, most CD4+ T cells had a memory phenotype and contained a significant population of cells expressing activation markers (CD25+, CD69+). Interestingly, the percent of CD69+ T cells was higher in synovial than IFP CD4+ T cells. Preliminary analyses indicated that the number of synovial CD4+ T cells were associated with VAS pain (β 0.51, 95% CI 0.09–1.02, p = 0.02). Conclusion. Our data suggest that the immune cell composition of the synovium and the IFP is similar, and includes activated cells that could contribute to inflammation through secretion of proinflammatory cytokines. Moreover, preliminary analyses indicate that synovial CD4+ T cells might associate with pain in patients with endstage OA of the knee.


This study focuses on student learning of engineering design practices and the development of engineering thinking skills during participation in design-based curricular activities and will seek to answer the question: What evidence is present in students' engineering design project work of engineering learning? Student teams working in a STEM integration curricular module implemented in a fifth grade science classroom were analyzed. This study employs case study methods as a means to deeply analyze each team's work through content analysis of student classroom artifacts and video analysis. We use the Framework for Quality K-12 Engineering Education, with a particular focus on process of design, STEM content, engineering thinking, and communication, as a lens for analyzing the engineering thinking involved in student learning. This research aims to develop an initial understanding of how to identify these engineering learning outcomes in classrooms, with the overall goal of developing engineering assessment tools for classroom teachers. Evidence of student learning outcomes for these key engineering components was found throughout student work and student interactions, though varying levels of learning were shown by each group. This study demonstrates that it is possible to identify student learning of engineering processes within a design-based curriculum.


Active glutamine utilization is critical for tumor cell proliferation. Glutaminolysis represents the first and rate‐limiting step of glutamine utilization and is catalyzed by glutaminase (GLS). Activation of ErbB2 is one of the major causes of breast cancers, the second most common cause of death for women in many countries. However, it remains unclear whether ErbB2 signaling affects glutaminase expression in breast cancer cells. In this study, we show that MCF10A‐NeuT cell line has higher GLS1 expression at both mRNA and protein levels than its parental line MCF10A, and knockdown of ErbB2 decreases GLS1 expression in MCF10A‐NeuT cells. We further show that in these cells, ErbB2‐mediated upregulation of GLS1 is not correlated to c‐Myc expression. Moreover, activation of neither PI3K‐Akt nor MAPK pathway is sufficient to upregulate GLS1 expression. Interestingly, inhibition of NF‐κB blocks ErbB2‐stimulated GLS1 expression, whereas stimulation of NF‐κB is sufficient to enhance GLS1 levels in MCF10A cells, suggesting a PI3K‐Akt‐independent activation of NF‐κB upregulates GLS1 in ErbB2‐positive breast cancer cells. Finally, knockdown or inhibition of GLS1 significantly decreased the proliferation of breast cancer cells with high GLS1 levels. Taken together, our data indicate that ErbB2 activation promotes GLS1 expression via a PI3K‐Akt‐independent NF‐κB pathway in breast cancer cells, identifying another oncogenic signaling pathway which stimulates GLS1 expression, and thus promoting glutamine utilization in cancer cells. These findings, if validated by in vivo model, may facilitate the identification of novel biochemical targets for cancer prevention and therapy. J. Cell. Biochem. 115: 498–509, 2014. © 2013 Wiley Periodicals, Inc.


Nowadays, it is recognized that the main purpose for using prefabricated posts is the connection of the replacement for the missing coronal portion of the tooth to the remaining root structure, thereby providing retention for the crown. Prefabricated posts allow fast, cheap, and easy techniques.

The aim of the present work is to ascertain the influence of crown material, using a previously validated 3D finite element model, on teeth restored with prefabricated glass fibre posts. Porcelain and enamel-like crowns were compared studying the case of a 300 N load applied on the palatal side at an angle of 30° to the radicular axis, in the vestibular direction. The model predicted similar stress distributions in both post systems. Moreover, the stresses predicted when using the porcelain crown were smaller than the ones predicted without the final crown in a previous work, thus acting as a protection. Within the limitations of this study, it can be stated that using porcelain for restoring crowns will produce an alike success rate as when using a material with properties similar to those of enamel.


Background The use of Electronic Medical Records (EMR) is increasingly common. Little is known about the influence of EMR on resident learning, and little guidance is available for clinical teachers in the EMR setting. Objectives This study aims to examine the impact of EMR on Memorial University of Newfoundland (MUN) Family Medicine resident learning and to develop a teaching primer for clinical teachers. Methods Impact of EMR on resident learning was evaluated using a web survey and focus group discussions. Introductory letters with consent form and link to web survey were emailed to all MUN Family Medicine residents and Academic Family Medicine faculty preceptors. To achieve desirable response rate the web survey was sent three times over the 20-week survey period. Response frequencies were descriptively analyzed. Concordance and discordance between faculty and residents were evaluated. Six residents and four faculty preceptors participated in the focus group discussions. FGDs were analyzed using thematic analysis. Recurrent themes arising from the web survey and focus groups were compiled with results from the literature review to form a primer for clinical teaching. Results 34 of the 43 eligible residents (79%) and 16 of the 17 eligible faculty (95%) completed the survey. Approximately 70% of residents and 69% of faculty agreed that EMR generally improves resident learning. Impairment of resident communication with patients was rated as the most frequent deficit (50% and 36% respectively. rho= -0.25). The FGDs affirmed the web survey results that EMR generally improves resident learning and preceptor feedback, but noted that improvements can be made using targeted communication training, avoiding EMR distraction when giving feedback, and avoidance of resident over-reliance on EMR templates and prescribing functions. Data is collated with a review of the literature in the form of a clinical primer to guide clinical teachers. Conclusions The rise of EMR has subtly changed the clinical supervision and instruction of medical learners. The results of this study contribute to the development of teaching strategies for enhancement of resident learning in the EMR setting. Targeted training for clinical teachers in the EMR setting may be of benefit to teachers and learners.


A hierarchical family of five three-dimensional potential energy surfaces has been developed for the benchmark He-CO system. Four surfaces were obtained at the coupled cluster singles and doubles level of theory with a perturbational estimate of triple excitations, CCSD(T), and range in quality from the doubly augmented double-zeta basis set to the complete basis set (CBS) limit. The fifth corresponds to an approximate CCSDT/CBS surface (CCSD with iterative triples/CBS, denoted CBS+corr). The CBS limit results were obtained by pointwise basis set extrapolations of the individual counterpoise-corrected interaction energies. For each surface, over 1000 interaction energies were accurately interpolated using a reproducing kernel Hilbert space approach with an R-6+R-7 asymptotic form. In each case, both three-dimensional and effective two-dimensional surfaces were developed. In standard Jacobi coordinates, the final CBS+corr surface has a global minimum at rCO=2.1322a0,R=6.418a0, and gamma=70.84 degrees with a well depth of -22.34 cm-1. The other four surfaces have well depths ranging from -14.83 cm-1 [CCSD(T)/d-aug-cc-pVDZ] to -22.02 cm-1 [CCSD(T)/CBS]. For each of these surfaces the infrared spectrum has been accurately calculated and compared to experiment, as well as to previous theoretical and empirical surfaces. The final CBS+corr surface exhibits root-mean-square and maximum errors compared to experiment (4He) of just 0.03 and 0.04 cm-1, respectively, for all 42 transitions and is the most accurate ab initio surface to date for this system. Other quantities investigated include the interaction second virial coefficient, the integral cross sections, and thermal rate coefficients for rotational relaxation of CO by He, and rate coefficients for CO vibrational relaxation by He. All the observable quantities showed a smooth convergence with respect to the quality of the underlying interaction surface.


Madhu ghrita is a herbal formulation containing honey and ghee (clarified butterfat) as its constituents. The aim of present study is to verify the wound healing and antiinflammatory claims of Madhu ghrita. Incision and excision wound models were used for evaluation of wound healing activity followed by histopathological study in which healing markers like keratinization, epithelization, fibrosis, neovascularisation and collagenation were evaluated in male Wistar rats. The results of Madhu ghrita were compared with the results of untreated control group and results of framycetine sulphate cream, considered as a positive control. The formulation was also tested for antiinflammatory activity, using carrageenan-induced paw oedema in male Wistar rats. The test formulation Madhu ghrita enhanced the tensile strength, which significantly improved over untreated wounds. The tensile strength of untreated control wound was 281±5.82, while with the Madhu ghrita and framycetine sulphate cream 1% w/w, it was 328±8.9 and 398±6.32, respectively. Treatment with Madhu ghrita alone promoted wound contraction and reduced the wound closure time, so increase in tensile strength and wound contraction shows the wound healing potential of Madhu ghrita . Histopathological study shows that proliferation of epithelial tissue promotes angiogenesis, multiplication of fibrous connective tissue due to treatment with Madhu ghrita . The test formulation Madhu ghrita also shows significant antiinflammatory activity when the results are compared with the activity of ibuprofen gel as reference standard. The present study demonstrates the wound healing and antiinflammatory potential of Madhu ghrita .


We have synthesized three nitrocompounds in order to mimic the model structure of some relevant drugs such as nifedipine. nitrendipine, nisoldipine, nimodipine, and related ones, in order to investigate the effect of structural change on its electrochemical and photodegradation properties. We have found that ortho substitution with a nitro group produces a distortion of the coplanar arrangement, thus decreasing the resonance interaction between the nitro group and the aromatic system. A consequence of this fact is the observed cathodic peak potential shift toward negative values in the ortho-substituted isomer. It is observed that the position of the nitro substitution also produced differences in the photostability of the studied compounds. Stability studies of the compounds in buffered solutions (pH 7) stored in room light conditions show that only the ortho derivative was unstable in the time scale of the experiment (2 h). The instability of the ortho derivative may be explained if we consider that in this isomer, the photoexcited state of the nitro group is not stabilized by resonance as a consequence of the loss of coplanarity between the nitro group and the aromatic ring. Using molecular modeling, we have found that the configuration of minimal energy shows torsion angles of 70, 7.5, and 2.2° for ortho- meta- and para-derivatives, respectively, confirming the lost of coplanarity between the nitro group and the aromatic ring in the ortho derivative.


Background/Aim: Increased nitric oxide (NO) generation and action have been suggested to be associated with glomerular hyperfiltration and increased vascular permeability early in diabetes. However, previous studies have primarily focused on the constitutive nitric oxide synthase (cNOS) pathway present in endothelial cells, and the role of the inducible NOS (iNOS) pathway in diabetic nephropathy has remained unclear. This study examined whether high glucose modulates NO synthesis by the iNOS pathway in rat mesangial cells. In addition, the effect of inhibition of the iNOS pathway on fibronectin production was determined to examine the role of the iNOS pathway in high glucose-induced extracellular expansion by mesangial cells. Methods: NO synthesis by the iNOS pathway was evaluated by nitrite and iNOS mRNA and protein productions. The effects of protein kinase C (PKC) inhibitor and aldose reductase inhibitor on the iNOS mRNA expression and aminoguanidine, a relatively specific inhibitor of the iNOS on fibronectin protein production were examined. Results: High 30 mM glucose concentration led to significant increases in nitrite production of rat mesangial cells upon stimulation with lipopolysaccharide (LPS) plus interferon-γ (IFN-γ) compared with control 5.6 mM glucose concentration. Mesangial iNOS mRNA expression and protein production also increased significantly in response to high glucose. The addition of calphostin C, a PKC inhibitor, and 6-bromo-1,3-dioxo-1H-benz[d,e]isoquinoline-2(3H)-acetic acid, an aldose reductase inhibitor, significantly suppressed the enhancement of iNOS mRNA expression in high glucose concentration. High glucose also significantly increased fibronectin protein production of mesangial cells upon stimulation with LPS plus IFN-γ compared to control glucose. Aminoguanidine reversed this high glucose-induced fibronectin production at dose inhibiting iNOS mRNA expression. Conclusions: These results indicate that high glucose enhances cytokine-induced NO production by rat mesangial cells, and that the activation of PKC and aldose reductase pathway may play a role in this enhancement. In addition, high glucose-induced NO production by the iNOS pathway may promote extracellular matrix accumulation by mesangial cells under certain condition.


Response inhibition is a cognitive process required to cancel an intended movement and can protect from danger. Functional magnetic resonance imaging (FMRI) studies showed that the dorsolateral prefrontal cortex (dlPFC) is a crucial brain region for response inhibition. Repetitive transcranial magnetic stimulation (rTMS) is a technique that can determine the contribution of specific cortical regions to behavior. Previous studies have found that repetitive transcranial magnetic stimulation of the dlPFC affects response inhibition. In the current study, we used transcranial direct current stimulation (tDCS), a non-invasive, painless brain stimulation technique with no known side effects, to alter neuronal excitability. A number of tDCS studies have suggested that tDCS may affect response inhibition. However, to date, limited work has been done to explore whether tDCS over the right dlPFC could alter response inhibition. Therefore, this study aimed to investigate the anodal stimulus effect of tDCS on response inhibition. We hypothesized that exciting the neural activity of the right dlPFC with anodal tDCS would enhance the ability of response inhibition. A 34 healthy subjects males, females) participated this within-subjects study. Stop-signal task (SST) was established with E-prime software. Participants received both active and sham stimulation on separate days. SST was used to measure the participants' capacity for response inhibition. In the active stimulation condition, we delivered a 1.5 mA direct current for 25 min (fade-in/fade-out time: 8 s); in the sham condition, we delivered a 1.5 mA direct current for 30 s at the beginning and 30 s at the end of the stimulation time. Anodal and cathodal stimulation electrodes were placed on F4 and FP1, respectively. Participants completed the SST, Stroop color-word matching task, Verbal Fluency test, and Digit Span test before and after the stimulation. We first calculated the mean reaction time (RT)in the go trials and stop-signal delay for each participant using ANALYZE-IT software. To calculate the individual stop-signal reaction time (SSRT), ANALYZE-IT first computes the mean RTs for all trials without a stop signal and then subtracts the mean stop-signal delay from this value. We performed a series of paired samples t-tests to compare the SSRT of each experimental condition with the SSRT of the sham and active conditions. There were no significant differences in SSRT pre-stimulation in sham or active stimulations, indicating equal response inhibition capacity among the participants. Interestingly, the difference in SSRT before and after stimulation was statistically significant in the active condition, t (33) =  2.25, p < 0.05, Cohens d = 0.38. This demonstrates that participants who received anodal stimulation over the right dlPFC had significantly reduced SSRT change scores on the SST compared to participants in the sham condition. This study demonstrated that transcranial electrical stimulation of the right dlPFC can regulate response inhibition, in that anodal stimulation improved participants' response inhibition. We confirm previous work suggesting that the right dlPFC is an important brain region of response


Perhaps the most brilliant comic strip ever created, "Calvin and Hobbes" continues to entertain with dazzling cartooning and tremendous humor.Bill Watterson's "Calvin and Hobbes" has been a worldwide favorite since its introduction in 1985. The strip follows the richly imaginative adventures of Calvin and his trusty tiger, Hobbes. Whether a poignant look at serious family issues or a round of time-travel (with the aid of a well-labeled cardboard box), "Calvin and Hobbes" will astound and delight you. Beginning with the day Hobbes sprang into Calvin's tuna fish trap, the first two "Calvin and Hobbes" collections, "Calvin and Hobbes" and "Something Under The Bed Is Drooling," are brought together in this treasury. Including black-and-white dailies and color Sundays, "The Essential Calvin and Hobbes" also features an original full-color 16-page story."


Abstract Isolated marginal tooth crowns of the early Campanian mosasaur Hainosaurus Dollo, 1885, from the Kristianstad Basin and the Vomb Trough, southern Sweden, are described and illustrated. The teeth have been collected from a narrow stratigraphic interval corresponding to the highest belemnite zone in the lower part of the European two-fold division of the Campanian stage. A reexamination of dental and skeletal characters in two alleged species of Hainosaurus, 'H.' pembinensis Nicholls, 1988 and 'H.' gaudryi (Thévenin, 1896), and detailed comparisons with the corresponding elements in H. bernardi Dollo, 1885 and Tylosaurus proriger (Cope, 1869a), strongly indicate that 'H.' pembinensis and 'H.' gaudryi are both Tylosaurus Marsh, 1872. Diagnostic features of Hainosaurus include a very small infrastapedial process on the quadrate (conspicuous protuberance in Tylosaurus), flattened, symmetrically bicarinate marginal teeth (asymmetric and conical in Tylosaurus), short and wide pygal centra, and anteriorly situated intermediate caudal vertebral centra with dorsoventrally thin transverse processes (markedly triangular centra and thick processes in Tylosaurus).


The altered levels of some essential trace elements and antioxidant minerals
have been observed in diabetic patients. Zinc, as an antioxidant and essential trace element, plays a
significant role in the function of many enzymes. Altered zinc content seems to be one of the
contributing factors in the pathogenesis of this disease. The purpose of this study was to investigate
serum level of zinc (Zn) and the correlation between zinc and fasting blood sugar (FBS) in patients
with type 2 diabetes mellitus (T2DM) and their first-degree relatives (FDR).
Methods & Materials: 46 subjects with T2DM, 46 FDR and 50 healthy subjects were involved in this
study. Serum concentrations of Zn were measured by colorimetric kit (Biorex, UK). Fasting blood
sugar was assayed using the standard kit (made by Pars Azmoon Inc., Tehran, Iran).
Results: We found decreased levels of Zn (P<0.001) in FDR when compared to healthy controls. FBS
levels were negatively correlated with Zn (r=0.431,P=0.003) in patients with T2DM. However, there
was no correlation between FBS level and Zn (r=0.024,P=0.8) in FDR.
Conclusion: Finally, patients with T2DM and their FDR has altered metabolism of Zn which may
contribute to increased risk of developing T2DM later on in FDR's life.


Telling Stories overturns traditional definitions of narrative by arguing that any story, whether a Bette Davis film, a jeans ad, a Jane Austen novel of a 'Cathy' comic, must be related to larger cultural networks. The authors show how meanings and subjectivity do not exist in isolation, but are manufactured by the narratives our culture reads and watches every day. They call for a critical practice that, through the fracturing of texts, can alter the grounds of knowledge and interpretation. This timely study will interest critics of narrative and culture, as well as students wanting to extend post-Saussurean theories to poopular and canonical cultures, and to the dynamics of story-telling itself.


Barremian-Aptian carbonate sediments in southern Provence belong to a drowning sequence within an intra-shelf basin and display organic-carbon-rich horizons corresponding to the demise of a rudists platform system and the onset of dysaerobic conditions. These horizons depart from the classical anoxic model accepted for most marine organic-carbon-rich deposits. They have a rich and diverse fauna documenting nutrient-rich waters with low oxygen content--an environment in which organic matter is preserved from both biological and chemical degradation. Sedimentological, geochemical and palaeoecological investigations suggest that the organic-carbon-rich carbonates reflect dysaerobic conditions favourable for organic matter preservation, the amount of dissolved oxygen being lower than the geochemical threshold for organic matter decay. These organic-carbon-rich sediments are the result of high sea surface productivity and sea bottom conditions favouring preservation. The kerogen is mainly amorphous sapropelic organic matter, essentially algal, with a high hydrogen index and is of marine origin, deposited during high sea-level.


Engineering T cells to treat autoimmunity Autoimmune diseases such as lupus and rheumatoid arthritis lack therapies that specifically target only the disease-causing cells. Inspired by the clinical success of using chimeric antigen receptor T cells to treat certain types of cancers, Ellebrecht et al. asked whether a similar approach might also work against antibody-driven autoimmune diseases. They engineered T cells to express chimeric receptors consisting of the disease-causing autoantigen desmoglein 3 fused to signaling domains that activate T cells. When given to diseased mice, the engineered T cells targeted and killed B cells that express antibodies targeting desmoglein 3, hinting that such a strategy may be an effective way to treat antibody-driven autoimmune diseases. Science, this issue p. 179 A proof-of-principle study indicates that engineered T cells may be an effective, targeted therapy for autoimmunity. Ideally, therapy for autoimmune diseases should eliminate pathogenic autoimmune cells while sparing protective immunity, but feasible strategies for such an approach have been elusive. Here, we show that in the antibody-mediated autoimmune disease pemphigus vulgaris (PV), autoantigen-based chimeric immunoreceptors can direct T cells to kill autoreactive B lymphocytes through the specificity of the B cell receptor (BCR). We engineered human T cells to express a chimeric autoantibody receptor (CAAR), consisting of the PV autoantigen, desmoglein (Dsg) 3, fused to CD137-CD3ζ signaling domains. Dsg3 CAAR-T cells exhibit specific cytotoxicity against cells expressing anti-Dsg3 BCRs in vitro and expand, persist, and specifically eliminate Dsg3-specific B cells in vivo. CAAR-T cells may provide an effective and universal strategy for specific targeting of autoreactive B cells in antibody-mediated autoimmune disease.


Estimates of phylogenetic relationships among fossil taxa implicitly provide hypotheses about the quality of the fossil record. Phylogenetic inferences also provide hypotheses about character evolution. The likelihood of any hypothesis that makes predictions about two data sets is simply the likelihood of the hypothesis given the first data set times the likelihood of the same hypothesis given the second data set. In this case, data set 1 represents stratigraphy and data set 2 represents morphology. Statistical methods exist for determining the likelihood of hypothesized levels of sampling. The likelihood of a hypothesized amount of character change yielding a particular most-parsimonious solution (i.e, L[hypothesized length | parsimony length] can be evaluated with simulations. A reanalysis of hyaenid phylogeny based on published character and stratigraphic data is presented here, using the maximum likelihood method. Two trees are found, depending on assumptions about ambiguous species, which are 11 and 10 steps longer than the most parsimonious tree (61 or 60 vs. 50 steps). However, the trees invoke far less stratigraphic debt (9 or 12 units vs. 47 units as measured in Mammal Zones). An important feature of the results is that the most likely tree length given hyaenid character data is estimated to be 56 to 62 steps (depending on the model of character evolution) rather than 50 steps. The likelihood tree suggests stronger trends toward bone-crushing specializations than does the parsimony tree and further suggests that high levels of homoplasy caused parsimony to underestimate the true extent of those trends. Simulations based on the character data and fossil record of hyaenids suggest that the maximum likelihood method is better able to estimate correct trees than is parsimony and somewhat better able to do so than previously proposed phylogenetic methods incorporating stratigraphy.


High dimensional data means that the number of variables p if far larger than the number of observations n. This occurs in several fields such as genomic data or chemometrics. This didactic talk starts from a survey of various solutions in linear regression and present afterwards their extensions to unsupervised « sparse » methods for principal components analysis (PCA) and multiple correspondence analysis (MCA).

When pn the OLS estimator does not exist for linear regression. Since it is a case of forced multicollinearity, one may use regularized techniques such as ridge regression, principal component regression or PLS regression: these methods provide rather robust estimates through a dimension reduction approach or with explicit (or not) constraints on the regression coefficients. The fact that all the predictors are kept is often considered as a positive point.
However if pn it becomes a drawback since a combination of all variables cannot be interpreted. Sparse combinations, ie with a large number of zero coefficients are preferred. Lasso, elastic net, sparse PLS perform simultaneously regularization and variable selection thanks to non quadratic penalties: L1, SCAD etc. We will present variants such as the group-lasso when the variables are structured in blocks.

In PCA, the singular value decomposition shows that if we regress principal components onto the input variables, the vector of regression coefficients is equal to the factor loadings. It suffices to adapt sparse regression techniques to get sparse versions of PCA and of PCA with groups of variables. We conclude by a presentation of a sparse version of Multiple Correspondence Analysis.


Multimedia service users can require multiservices according to their own environment for accessing to public networks. For copying with customer-oriented service requirements, network providers have to prepare multi-layer service networks. This paper deals with frame relay, ATM and IP networking services on multi-layer networks. In order to provide multiple data services, network provider needs to define and make use of client-server and interworking relationships between these networks. In this paper, we propose a service management architecture in order to efficiently manage multiple services and network resources from service point of view. The proposed service management architecture includes functionalities such as subscription management, customer-network management, communication session management, and business layer support management. Especially, it describes an information model for managing multi-layer networks by way of the interworking or clientserver relationship. The proposed functionalities are modeled in accordance with the object-oriented modeling concept and implemented on a CORBA platform. The applications on the proposed architecture include VPN services and various statistical services for customers and the carrier. The realized system is to be used for Koera Telecom's high speed networks mainly for supporting Internet services. key words: service management, CORBA, TINA, ATM VPN,


Fragmented, unfocused, and top down approaches to professional development are unrealistic, ineffective and do not promise anything significant to teachers and their contexts. This paper questions professional development for tertiary teachers in Pakistan. It does so from the perspectives of Pakistani tertiary teachers gained through a qualitative, ethnographic case study. The analysis of these previously unheard voices revealed themes that expand our understanding of the problematic nature of professional development. The results of this study indicate the need to reform professional development and to assist in these reforms, the study suggests that teachers need to gain a wide repertoire of teaching to become better practitioners. To do so, a school-based provision of professional development with social learning as the pedagogy is preferred as a design.


Modeling Internet growth is important both for understanding the current network and to predict and improve its future. To date, Internet models have typically attempted to explain a subset of the following characteristics: network structure, traffic flow, geography, and economy. In this paper we present a discrete, agent-based model, that integrates all of them. We show that the model generates networks with topologies, dynamics, and more speculatively spatial distributions that are similar to the Internet.


We analyse the effects of retirement of one partner on home production by both partners in a couple. Using longitudinal data from Germany on couples, we control for fixed household specific effects to address the concern that retirement decisions are correlated with unobserved characteristics that also affect home production. For males and females, we find that own retirement significantly increases the amounts of home production. There are negative cross-effects of retirement on home production done by the partner. The fall in household income at retirement of one of the partners is largely compensated by an increase in total household production.