New Horizons unveils the Pluto system In July 2015, the New Horizons spacecraft flew through the Pluto system at high speed, humanity's first close look at this enigmatic system on the outskirts of our solar system. In a series of papers, the New Horizons team present their analysis of the encounter data downloaded so far: Moore et al. present the complex surface features and geology of Pluto and its large moon Charon, including evidence of tectonics, glacial flow, and possible cryovolcanoes. Grundy et al. analyzed the colors and chemical compositions of their surfaces, with ices of H2O, CH4, CO, N2, and NH3 and a reddish material which may be tholins. Gladstone et al. investigated the atmosphere of Pluto, which is colder and more compact than expected and hosts numerous extensive layers of haze. Weaver et al. examined the small moons Styx, Nix, Kerberos, and Hydra, which are irregularly shaped, fast-rotating, and have bright surfaces. Bagenal et al. report how Pluto modifies its space environment, including interactions with the solar wind and a lack of dust in the system. Together, these findings massively increase our understanding of the bodies in the outer solar system. They will underpin the analysis of New Horizons data, which will continue for years to come. Science, this issue pp. 1284, 10.1126/science.aad9189, 10.1126/science.aad8866, 10.1126/science.aae0030, & 10.1126/science.aad9045 Pluto's atmosphere is cold, rarefied, and made mostly of nitrogen and methane, with layers of haze. INTRODUCTION For several decades, telescopic observations have shown that Pluto has a complex and intriguing atmosphere. But too little has been known to allow a complete understanding of its global structure and evolution. Major goals of the New Horizons mission included the characterization of the structure and composition of Pluto's atmosphere, as well as its escape rate, and to determine whether Charon has a measurable atmosphere. RATIONALE The New Horizons spacecraft included several instruments that observed Pluto's atmosphere, primarily (i) the Radio Experiment (REX) instrument, which produced near-surface pressure and temperature profiles; (ii) the Alice ultraviolet spectrograph, which gave information on atmospheric composition; and (iii) the Long Range Reconnaissance Imager (LORRI) and Multispectral Visible Imaging Camera (MVIC), which provided images of Pluto's hazes. Together, these instruments have provided data that allow an understanding of the current state of Pluto's atmosphere and its evolution. RESULTS The REX radio occultation determined Pluto's surface pressure and found a strong temperature inversion, both of which are generally consistent with atmospheric profiles retrieved from Earth-based stellar occultation measurements. The REX data showed near-symmetry between the structure at ingress and egress, as expected from sublimation driven dynamics, so horizontal winds are expected to be weak. The shallow near-surface boundary layer observed at ingress may arise directly from sublimation. The Alice solar occultation showed absorption by methane and nitrogen and revealed the presence of the photochemical products acetylene and ethylene. The observed nitrogen opacity at high altitudes was lower than expected, which is consistent with a cold upper atmosphere. Such low temperatures imply an additional, but as yet unidentified, cooling agent. A globally extensive haze extending to high altitudes, and with numerous embedded thin layers, is seen in the New Horizons images. The haze has a bluish color, suggesting a composition of very small particles. The observed scattering properties of the haze are consistent with a tholin-like composition. Buoyancy waves generated by winds flowing over orography can produce vertically propagating compression and rarefaction waves that may be related to the narrow haze layers. Pluto's cold upper atmosphere means atmospheric escape must occur via slow thermal Jeans' escape. The inferred escape rate of nitrogen is ~10,000 times slower than predicted, whereas that of methane is about the same as predicted. The low nitrogen loss rate is consistent with an undetected Charon atmosphere but possibly inconsistent with sublimation/erosional features seen on Pluto's surface, so that past escape rates may have been much larger at times. Capture of escaping methane and photochemical products by Charon, and subsequent surface chemical reactions, may contribute to the reddish color of its north pole. CONCLUSION New Horizons observations have revolutionized our understanding of Pluto's atmosphere. The observations revealed major surprises, such as the unexpectedly cold upper atmosphere and the globally extensive haze layers. The cold upper atmosphere implies much lower escape rates of volatiles from Pluto than predicted and so has important implications for the volatile recycling and the long-term evolution of Pluto's atmosphere. MVIC image of haze layers above Pluto's limb. About 20 haze layers are seen from a phase angle of 147°. The layers typically extend horizontally over hundreds of kilometers but are not exactly horizontal. For example, white arrows on the left indicate a layer ~5 km above the surface, which has descended to the surface at the right. Observations made during the New Horizons flyby provide a detailed snapshot of the current state of Pluto's atmosphere. Whereas the lower atmosphere (at altitudes of less than 200 kilometers) is consistent with ground-based stellar occultations, the upper atmosphere is much colder and more compact than indicated by pre-encounter models. Molecular nitrogen (N2) dominates the atmosphere (at altitudes of less than 1800 kilometers or so), whereas methane (CH4), acetylene (C2H2), ethylene (C2H4), and ethane (C2H6) are abundant minor species and likely feed the production of an extensive haze that encompasses Pluto. The cold upper atmosphere shuts off the anticipated enhanced-Jeans, hydrodynamic-like escape of Pluto's atmosphere to space. It is unclear whether the current state of Pluto's atmosphere is representative of its average state—over seasonal or geologic time scales.


By photoionizing cold, trapped atoms it is possible to produce ultracold plasmas with temperatures in the vicinity of 1 K, roughly 4 orders of magnitude colder than conventional cold plasmas. After the first photoelectrons leave, the resulting positive charge traps the remaining electrons in the plasma. Monitoring the dynamics of the expansion of these plasmas shows explicitly the flow of energy from electrons to the ionic motion, which is manifested as the expansion of the plasma. The electron energy can either be their initial energy from photoionization or can come from the energy redistribution inherent in recombination and superelastic scattering from recombined Rydberg atoms. If the cold atoms are excited to Rydberg states instead of being photoionized, the resulting cold Rydberg gas quickly evolves into an ultracold plasma. After a few percent of the atoms are ionized by collisions or blackbody radiation, electrons are trapped by the resulting positive charge, and they quickly lead to ionization of the Rydberg atoms, forming a plasma. While the source of this energy is not clear, a likely candidate is superelastic scattering, also thought to be important for the expansion of deliberately made plasmas.


Gating of sensory (e.g. auditory) information has been demonstrated as a reduction in the auditory-evoked potential responses recorded in the brain of both normal animals and human subjects. Auditory gating is perturbed in schizophrenic patients and pharmacologically by drugs such as amphetamine, phencyclidine or ketamine, which precipitate schizophrenic-like symptoms in normal subjects. The neurobiological basis underlying this sensory gating can be investigated using local field potential recordings from single electrodes. In this paper we use such technology to investigate the role of cannabinoids in sensory gating. Cannabinoids represent a fundamentally new class of retrograde messengers which are released postsynaptically and bind to presynaptic receptors. In this way they allow fine-tuning of neuronal response, and in particular can lead to so-called depolarization-induced suppression of inhibition (DSI). Our experimental results show that application of the exogenous cannabinoid WIN55, 212-2 can abolish sensory gating as measured by the amplitude of local field responses in rat hippocampal region CA3. Importantly we develop a simple firing rate population model of CA3 and show that gating is heavily dependent upon the presence of a slow inhibitory (GABAB) pathway. Moreover, a simple phenomenological model of cannabinoid dynamics underlying DSI is shown to abolish gating in a manner consistent with our experimental findings.


With extensive development of nanotechnology in last few years, scientists have discovered that nanoparticles (NPs) can be used as an efficient Drug Delivery System (DOS). In order to develop better NPs based drug delivery tool, it is imperative to understand the interaction between the NPs and the cell membrane. In our earlier studies, cerium oxide nanoparticles (CNPs) have been reported to have therapeutic properties, specifically against abnormalities associated with oxidative stress. Therefore, CNPs with different sizes and morphology were selected to understand the interaction with cell. We analyzed the mechanical property of human nasal septum tumor cells membranes using Atomic Force Microscopy (AFM) with and without CNPs. In particular, Force-Distance spectroscopy mode was used to estimate the elasticity of cells membrane. Different concentrations (0, 50, 125 and 250 µM) of CNPs were added to the cells (squamous cells; CCL30) and incubated for different time periods (0, 15, 30 and 60 minutes). Cell membrane elasticity/Young's modulus was calculated using a modified Hertz model. Changes in the cell elasticity were observed in high concentration of CNPs when treated with one hour. Significant changes in cell elasticity were observed at high concentration of CNPs for one hour of incubation. No significant change in cell elasticity was observed over one hour time period for 50 µM of CNPs. Moreover, by using selected inhibitors to block different cell mediated internalization pathways, we also investigated the correlation between the cellular uptake and the tracking of NPs with their size. Specifically, similar change in cell elasticity was observed after blocking the cell energy production for CNPs with smaller diameter (3-5 nm). On the other hand, bigger size NPs (20-30 nm) showed no change in cell elasticity after blocking the cell energy production. These results indicate that 3-5 nm particles internalize cell by non-energy dependent pathway i.e. passive diffusion whereas 20-30 nm particles entered in cell by energy dependent pathways i.e. endocytosis of particles. Further, we have also identified the cellular uptake of 20-30 nm particles is by enclosing those CNPs in membrane vesicles in caveolae-mediated endocytosis mechanism. In summary, these results indicate that the nanoparticles-cell interaction has pronounced influence on the shape and size of the nanoparticles. These interactions can be further monitored by real time mechanical property measurement of cell membrane.


Abstract Samples from Russia and Scotland are used to examine the interaction of the REE-Ti silicate chevkinite-(Ce) with hydrothermal fluids. Altered zones in crystals are distinguished by using areas of low intensity on backscattered-electron images, low analytical totals, increasingly large departures from stoichiometry and, in some cases, the presence of micropores. Initial alteration of the chevkinite results in strong Ca enrichment. With increasing degrees of alteration, Ca abundances drop sharply, as do those of the REE, Fe and Si. In contrast, Ti levels increase strongly, usually accompanied by higher Nb ± Th levels. The most altered zones contain up to 36 wt.% TiO2 and the formula cannot be expressed in the standard chevkinite formula. In detail, samples follow different alteration trends, presumably reflecting different P, T, fO₂ and fluid composition. The Ti enrichment may have been related to a reaction front of dissolution-reprecipitation passing through the outer zones of the original chevkinite, leaving behind a reprecipitated Ti-enriched phase which may or may not be chevkinite.


Fluorescence lifetime correlation spectroscopy (FLCS) has been used to probe the influence of PEG-8000 on the fluidity of fluorescently labeled planar supported lipid bilayers on ozone plasma treated glass. The lipid membrane compositions examined were; DOPC, DOPC/DOPS (80/20 mol/mol) and DMPC, with and without cholesterol. The lateral diffusion coefficients (D) for supported lipid bilayer films of these layers without cholesterol were 7.9 ± 0.2, 7.9 ± 0.4 and 5.5 ± 0.1 μm2 s−1 respectively. The high fluidity reflected the super-hydrophilicity (contact angle of 0) of the ozone treated plasma glass substrate. Using DOPE conjugated Atto 655 as a probe, exposure of the lipid bilayer to a 30% wt/wt aqueous solution of PEG, followed by washing, dramatically increased the diffusion coefficients of the probe within the film. For example, the diffusion coefficient for the DOPC bilayer increases by nearly an order of magnitude to 51.4 ± 2.6 μm2 s−1. The autocorrelation curves for DOPC/DOPS (80/20 mol/mol) and DMPC bilayers required a two-component model for adequate fit of their behaviour yielding both fast and slow components of the diffusion. In all cases, when hydrophilic DOPE–Atto 655 was used as the probe, treatment of the lipid bilayer with PEG resulted in non-Brownian diffusion. Importantly, the observed diffusion behavior observed depends on the identity of probe. In contrast, when a hydrophobic probe (DOPE–NapthBodipy) was employed PEG showed relatively little impact on the observed diffusion rates. This was attributed to orientation of the reporter probe in the lipid bilayer and its aqueous interface. Specifically, DOPE–Atto 655 is believed to associate strongly with PEG mesh at the aqueous interface of the lipid bilayer, its diffusion strongly influenced by the structure in this region, whereas DOPE–NapthBodipy remains in the interior of the bilayer where it is relatively uninfluenced by PEG.


Seeded growth of tetrapropylammonium (TPA)-silicalite-1 is studied using simulations and dynamic light scattering, atomic force microscopy, and transmission electron microscopy experiments. The effects of the total silica concentration, temperature, and total seed concentration are examined. When the composition of silica in solution is above a critical value, growth is observed. In such a case, the size of the seeds increases linearly with time, with a growth rate that is not significantly affected by the total silica concentration. Growth appears to be activated with an activation energy of 90 kJ/mol for a range of seed concentrations. Transmission electron microscopy and dynamic light scattering indicate the presence of subcolloidal particles. Simulations of the growth of a static particle in a suspension of subcolloidal particles are carried out. Good agreement with experimental results regarding the growth rate and the apparent activation energy is possible by considering DerjaguinLandau-Verwey-Overbeek (DLVO) interactions with electrostatic repulsion described with a constant surface charge model. The type of interaction was also verified with atomic force microscopy force measurements between a silicalite surface and a glass sphere. By use of these types of interactions, it is also possible to explain the stability of the seeded suspension and show that only a relatively narrow size distribution of growth precursors participate in the growth of the seeds. Our results support the possibility that under the conditions studied, growth of silicalite seeds proceeds by a mechanism with the rate-limiting step being the addition of subcolloidal particles.


BACKGROUND
Juvenile nasopharyngeal angiofibroma (JNA) is a rare tumor of adolescent males and there is a paucity of Indian studies on this subject.

AIMS
To present the experience of management of JNA at a single institution.

SETTING AND DESIGN
This is a retrospective observational study of patients with JNA who presented at the Tata Memorial Hospital between May 1988 and August 2001.

MATERIALS AND METHODS
Thirty-two patients with JNA were treated in the study period. Since the time period was prolonged and diagnostic and therapeutic protocols had undergone many changes, the patients were divided into two groups, namely 1988-1996 and 1997-2001. The age distribution, disease patterns, management approaches and treatment outcomes of patients in the two groups were recorded. Statistical analyses were done using students 't' test and test for proportion.

RESULTS
The mean age at presentation was 16 years and more than 90% of the patients had Stage III or IV disease. Preoperative embolization was carried out in 19 patients. The surgical approaches used were median maxillectomy, infratemporal fossa, transpalatal, maxillary swing and craniofacial approach. The recurrence rate, complete resection rate and cure rates were 12.5%, 41% and 63% respectively.

CONCLUSION
Surgery is the mainstay of treatment of JNA. Preoperative embolization and newer surgical approaches result in less blood loss and complete resection. Aggressive re-resection should be done for resectable recurrences reserving radiotherapy for unresectable, recurrent/ residual disease.


SharePoint 2010 is todays leading presentation and deployment system for Business Intelligence (BI) solutions based on Microsoft technologies. This book brings together all the information you need to successfully implement and use SharePoint 2010s powerful BI capabilities. It reflects the unsurpassed real-world experience of five expert consultants at RDA, a Microsoft Gold Partner specializing in delivering advanced BI solutions with SharePoint. Youll first learn how to prepare SharePoint 2010 for the deployment of BI solutions. Next, the authors walk through integrating, configuring, and using Reporting Services, PerformancePoint Services, PowerPivot, Visio Services, and other key related technologies. Building on what youve learned, youll walk step-by-step through constructing and integrating two end-to-end BI solutions. Finally, in a comprehensive troubleshooting section, the authors present todays most common SharePoint BI issues, identify proven solutions, and teach effective problem-solving techniques. Get started fast, by using the Business Intelligence Centers prebuilt site collection and template Build integrated, end-to-end SharePoint BI solutions Present business data to the enterprise through Excel Services Install, configure, and integrate Reporting Services and the Reporting Services Add-In for SharePoint Define document library content types and manage reports Use Report Viewer Web Parts to render reports on SharePoint web pages Build enterprise dashboards with PerformancePoint Services Secure dashboards via data source delegation, SharePoint permissions, and groups Analyze enormous datasets with PowerPivot for Excel and SharePoint Publish Visio 2010 data-driven web diagrams that integrate multiple data sources Utilize the fine-grained security available through Visio Graphics Service Troubleshoot problems with Reporting Services, PerformancePoint Services, PowerPivot, and Visio Services


Nowadays cities invest more in their public services, and particularly digital ones, to improve their resident's quality of life and attract more people. Thus, new crowdsourcing services appear and they are based on contributions made by mobile users equipped with smartphones. For example, the respect of the traffic code is essential to ensure citizens' security and welfare in their city. In this paper, we present CrowdOut, a new mobile crowdsourcing service for improving road safety in cities. CrowdOut allows users to report traffic offence they witness in real time and to map them on a city plan. CrowdOut service has been implemented and experiments and demonstrations have been performed in the urban environment of the Grand Nancy, in France. This service allows users appropriating their urban environment with an active participation regarding the collectivity. This service also represents a tool for city administrators to help for decisions and improve their urbanization policy, or to check the impact of their policy in the city environment.


, states that "Independent criteria identifying the characteristics of a new-generation comnmn computer language must be developed." In commenting on this point in a letter to Congressman Brooks [SIGPLAN Notices 2, 12 (Dec. 1967), 55, 56], I found it necessary to strip away his supporting arguments and restate his proposal more briefly, but largely in his own words, as follows: Moved by the likelihood that '% less than the best" language, PL/I, "could become by default, the de facto language of the next generation," you propose the setting up of a group of "the best minds in the entire data processing community" to develop "independent criteria identifying the characteristics of a new generation common computer language." Whereupon, "under improved USASI procedures, ... changes in PL/I" (or perhaps even a brand new language) would be proposed "to meet the general criteria," and "it would then be reasonable to expect IBM ... to adopt" the results. Certainly PL/I has many faults. It is poorly defined, it lacks a certain parsimony of design, it does not always make full and obvious use of many of the powerful concepts it employs, and it is by no means as widely applicable as it could be. Yet it is a valuable language, and who can tell if these faults detract greatly from its practical utility as a programming tool? Nevertheless, to develop a better language to eventually replace it is surely a worthwhile and, I believe, an important national goal. A Federal initiative toward this goal should be welcome though I expect some will not welcome it. But the main problem is not in establishing better criteria and designing an improved language; in addition, a more valuable language must be created. And the economic value of a language is determined net so much by its technical excellence, or the lack of it, but by how much time, money and intellectual effort people can be persuaded to invest in developing and using it. With the technical authority of a group of acknowledged experts behind it, and with the full economic authority of the major computer user, the Federal Government, supporting it, success in establishing an improved and more valuable language can no doubt be achieved-as the history behind the current investment in COBOL might seem to indicate, except that this very investment makes the present j ob harder. Yet it is an important j ob-too important, I …


We here investigate polarimetric behavior of thick samples of porcine liver, Intralipid, and microsphere-based tissue phantoms whose absorption and scattering properties are matched. Using polarized light we measured reflection mode Mueller matrices and derived linear/circular/total depolarization rates, based on polar decomposition. According to our results, phantoms exhibit greater depolarization rates in the backscattering geometry than the liver sample. The enhanced tissue polarization preservation differs from previous reports of polarimetric transmission studies, with the likely cause of this difference being the angular dependence of the single-scattering phase function. Also, Intralipid approximated polarimetric liver behavior well, whereas the polystyrene phantoms did not.


Trade has been considered a condition for growth and development, a view that might have merits in explaining the rise of the Western world. I use a new data set from archival sources of eighteenth-century China to revisit this question. This analysis suggests previous studies of market integration, which attribute much growth to a reduction in transport costs, have overestimated these effects. Ifind the overall level of market integration in China was higher than previously thought, and, intertemporal effects are important substitutes for trade. Both factors reduce the importance of trade as a unique explanation for subsequent growth. (JEL 013, 018, R1l, N25)


The growing influence and self-confidence of local authorities count among the most interesting recent phenomena in global governance. While not entirely oblivious, international law as a field has struggled to get ahead of this dynamic, focusing instead on how to integrate local authorities into static conventional frameworks firmly based on the notion of state sovereignty. However, as a discussion of the global state of affairs and a focus on human rights cities shows, local actors increasingly claim and obtain a key role in the realization of international law. Additionally, they hold important potential to address some of the most pressing challenges to international human rights law concerning its efficacy and legitimacy. This article therefore calls for a proactive approach to the study of local authorities that considers local authorities as a 'new frontier' in international law generally and in human rights law specifically. It proposes a critical research agenda for this purpose that could produce important new insights into (i) the continued relevance and legitimacy of human rights as a discourse of governance; (ii) the bearing of domestic constitutional arrangements on the implementation of human rights law and (iii) questions of, and possible shifts in, legal subjecthood in the contexts of 'state failure'.


Computer games have reached the lives of millions of people worldwide. Today, these games have become a popular source of entertainment especially to students. Therefore, this research is intended to study the effects of playing computer games on noncomputer science students' performance particularly in a computer-related subject at UiTM Terengganu. This research goes through five activities: (1) Review previous research to determine significance of the next research, (2) Preliminary study on category of computer games, (3) Develop and disseminate research instruments, (4) Analyze collected data using statistical methods, and (5) Conclusion and documentation. Questionnaires were distributed to CSC134 students where their background and experience were evaluated in order to seek information on their habitual patterns of playing computer games and understand how computer games might affect them in their studies. The result shows that more than half of the students like to play computer games. A majority of these students prefer playing Card and Arcade type of games and spent time playing at least twice a week for the duration of more than three hours each time. One of the important findings is that early exposure to computer games does not have any profound effect on overall students' achievement in CSC134. However due to the familiarization of using computers, the students performed better in their laboratory assessments. Even though playing games does not assure good results in CSC134 course, nearly 88% of them passed the course.


The Border Gateway Protocol (BGP) is an interdomain routing protocol that allows each Autonomous System (AS) to define its own routing policies independently and use them to select the best routes. By means of policies, ASes are able to prevent some traffic from accessing their resources, or direct their traffic to a preferred route. However, this flexibility comes at the expense of a possibility of divergence behavior because of mutually conflicting policies. Since BGP is not guaranteed to converge even in the absence of network topology changes, it is not safe. In this paper, we propose a randomized approach to providing safety in BGP. The proposed algorithm dynamically detects policy conflicts, and tries to eliminate the conflict by changing the local preference of the paths involved. Both the detection and elimination of policy conflicts are performed locally, i.e. by using only local information. Randomization is introduced to prevent synchronous updates of the local preferences of the paths involved in the same conflict.


ISPC, NEPAD and ECDPM stimulated discussion between agricultural researchers and corridor stakeholders on their contributions to inclusive and sustainable development. Spatial development initiatives (SDI), including corridors, aim to coordinate and concentrate investment on transport infrastructure (typically building new roads or upgrading existing ones, often related to access for exploiting mineral resources – and accompanying logistic infrastructure (transport services, storage capacity, agricultural extension services – i.e. soft infrastructure. The cooperation among institutions required to coordinate such efforts involves the national governments of the countries concerned, the private sector, international donors, development institutions and researchers. Corridors are becoming priorities in developing countries, as governments and aid agencies are investing heavily in them to try and facilitate dynamism in rural areas. FAO has recently carried out a comparative analysis to establish a corridor typology, to identify the main drivers and components of corridors and to develop policy decision support tools and checklists. A large part of this cross-comparison focuses on the agricultural component of corridor interventions, identifying the most recurrent activities under this component, the financial resources involved, the most often selected subsectors or value chains and target markets, the interface between infrastructure and agro-industrial development and the positive or negative impacts of corridor interventions on the agricultural sector. Growth corridor initiatives like the SAGCOT in Tanzania sometimes spur heated debate. On the one hand, corridors can attract and direct public and private investment towards a sustainable increase in production and income; on the other, corridors are accused of imposing a model that encourages land grabbing, mono-cropping and exclusion of small scale farmers and entrepreneurs. Which one of these visions reflects reality most accurately, remains unclear. The debate is not helped by a lack of undisputed evidence1. The workshop brought together some of the key institutions and researchers that are active on this topic both from within and outside the CGIAR2, with the objectives of understanding the current state of thinking in research and policy circles, and to help define how best the ISPC might contribute through its strategic study on corridors and spatial development initiatives in African Agriculture.


The objective of this research is to develop a smart adjustable standing-sitting wheelchair prototype that can be operated with a smartphone. Its distinctive feature is the ability of standing-sitting adjustment and automatic stop when approaching obstacles. This device can be controlled from installed joysticks and Android smartphone control program. Arduino microcontroller is the main processing unit to control drive system operating. A Linear actuator is used for standing-sitting adjustment. An ultrasonic sensor is used to make the smart wheelchair stop automatically when detect obstacles. A wheelchair tested showed that it can move at a speed of approximately 3 kilometers per hour, take 14.30 seconds for standing upright adjustment, release down 13.56 seconds, and average automatic stopping distance is 43 centimeters.


In recent years, universities have been under increased pressure to adopt e-learning practices for teaching and learning. In particular, the emphasis has been on learning management systems (LMSs) and associated collaboration tools to provide opportunities for sharing knowledge, building a community of learners, and supporting higher order learning and critical thinking through conversation and collaboration. Due to the greater level of data continuity, reliability, and privacy that LMSs can provide compared to the available free applications, LMSs are still the central platform for many universities to deliver e-learning. Therefore, it is vital to investigate the LMS structure requisites that affect user engagement. This paper focuses on the important LMS design factors that influence user engagement with e-learning tools within LMSs. Results were extracted from 74 interviews about Blackboard with students and lecturers within a major Australian university. A user-friendly structure, avoidance of too many tools and links, support for privacy and anonymous posting, and more customisable student-centred tools were identified as LMS design factors that affect user engagement.


This new edition of the leading text on business and government focuses on the insights economic reasoning can provide in analyzing regulatory and antitrust issues. Departing from the traditional emphasis on institutions, Economics of Regulation and Antitrust asks how economic theory and empirical analyses can illuminate the character of market operation and the role for government action and brings new developments in theory and empirical methodology to bear on these questions. The fourth edition has been substantially revised and updated throughout, with new material added and extended discussion of many topics. Part I, on antitrust, has been given a major revision to reflect advances in economic theory and recent antitrust cases, including the case against Microsoft and the Supreme Court's Kodak decision. Part II, on economic regulation, updates its treatment of the restructuring and deregulation of the telecommunications and electric power industries, and includes an analysis of what went wrong in the California energy market in 2000 and 2001. Part III, on social regulation, now includes increased discussion of risk-risk analysis and extensive changes to its discussion of environmental regulation. The many case studies included provide students not only pertinent insights for today but also the economic tools to analyze the implications of regulations and antitrust policies in the future. The book is suitable for use in a wide range of courses in business, law, and public policy, for undergraduates as well at the graduate level. The structure of the book allows instructors to combine the chapters in various ways according to their needs. Presentation of more advanced material is self-contained. Each chapter concludes with questions and problems.


Acute myeloid leukemia (AML) with t(8;21) rearrangement, constitutes about 5% of all AML cases and is characterized by the presence of RUNX1-RUNX1T1 fusion gene. Although this subtype, referred as CBF leukemia, belongs to the favorable cytogenetic risk group, 25% to 30% of the patients relapse. Detection of minimal residual disease (MRD) is of major importance since it evaluates the "depth" of the remission and therefore, risk adapted therapy based on early detection of relapse becomes feasible. RUNX1-RUNX1T1 fusion gene could be used for MRD detection using RQ-PCR.
Within this work, a sensitive, specific and easy to perform, calibrator normalized relative quantification with external standards assay for RUNX1-RUNX1T1 transcript levels, was established and has consequently been integrated in the routine diagnostic work-up of RUNX1-RUNX1T1 positive patients. ABL1 was used as a reference gene and cDNA of the Kasumi-1 cell line as a calibrator. Relative quantification was performed by calculating the RUNX1-RUNX1T1/ ABL1 ratio, which was further normalized to the RUNX1-RUNX1T1/ABL1 expression ratio of Kasumi-1 calibrator. Maximum sensitivity of the assays for both target and reference gene, was higher than 10-4 (5x10-4). The sensitivity of 5x10-4 was also confirmed using cDNA dilutions from Kasumi-1 cell line as well as dilutions of patients' cDNA. The specificity of the assay was determined when RUNX1-RUNX1T1 negative patients were tested; along with cDNA from negative cell lines and no amplification was observed.
184 samples from 39 patients, were quantified in order to assess the clinical usefulness of the assay. Transcript levels in 12 patients were measured on day 16 and were correlated to the clinical outcome. Moreover in 20 patients, comparison of the RUNX1-RUNX1T1 ratios at diagnosis and before consolidation revealed a 3 log10 decrease, which was also correlated to the disease outcome. 28% (11/39) of the patients in the study relapsed, consistent with previous studies.
Very importantly, due to the good correlation of RUNX1-RUNX1T1 transcripts with the disease course, this assay will also be used to monitor MRD of t(8;21) positive patients within the recently launched AMLCG2014 study.


Combined (estrogen and a progestogen) hormone replacement therapy (cHRT) is associated with an increased risk of breast cancer, while estrogen replacement therapy is not. Whatever the underlying mechanism, it is the progestogen in cHRT that seems to increase the risk. Fear of breast cancer is a major limiting factor in the use of hormone replacement therapy, and when women discontinue cHRT because of side effects, the latter are often attributable to the progestogen component. cHRT is given to women with an intact uterus to protect against the effects of un-opposed estrogen such as an increased risk of endometrial cancer. Estrogen replacement therapy suffices for women with a prior hysterectomy. There is a clear distinction in risk and side effect profile between cHRT and estrogen replacement therapy. Apart from being the most effective treatment for menopausal symptoms, estrogen prevents osteoporosis, and may also have a potential role in prevention of Alzheimer's Dementia, now the biggest killer of women in the United Kingdom. Evidence also suggests that progestogens could compromise the dementia-preventative effect of estrogen. Given the immense therapeutic and preventative potential of estrogen, the use of progestogens in cHRT needs re-appraisal. The levonorgestrel intrauterine system (LNg-IUS) could reduce breast cancer risk while protecting the endometrium. Other approaches to the safe use of progestogens await research.


Enterprise-class server appliances such as network-attached storage systems or network routers can benefit greatly from virtualization technologies. However, current inter-VM communication techniques have significant performance overheads when employed between highly-collaborative appliance components, thereby limiting the use of virtualization in such systems. We present Fido, an inter-VM communication mechanism that leverages the inherent relaxed trust model between the software components in an appliance to achieve high performance. We have also developed common device abstractions - a network device (MMNet) and a block device (MMBlk) on top of Fido.

We evaluate MMNet and MMBlk using microbench-marks and find that they outperform existing alternative mechanisms. As a case study, we have implemented a virtualized architecture for a network-attached storage system incorporating Fido, MMNet, and MMBlk. We use both microbenchmarks and TPC-C to evaluate our virtualized storage system architecture. In comparison to a monolithic architecture, the virtualized one exhibits nearly no performance penalty in our benchmarks, thus demonstrating the viability of virtualized enterprise server architectures that use Fido.


Soil fumigation is an important management practice for controlling soil pests and enabling successful replanting of orchards. Reducing emissions is required to minimize the possible worker and bystander risk and the contribution of fumigants to the atmosphere as volatile organic compounds that lead to the formation of ground-level ozone. A field trial was conducted in a peach orchard replant field to investigate the effects of fumigation method (shank-injection vs. subsurface drip-application treatments) and surface treatments (water applications and plastic tarps) on emissions of 1,3-dichloropropene (1,3-D) and chloropicrin (CP) from shank-injection of Telone C-35 and drip application of InLine. Treatments included control (no water or soil surface treatment); standard high-density polyethylene (HDPE) tarp, virtually impermeable film (VIF) tarp, and pre-irrigation, all over shank injection; and HDPE tarp over and irrigation with micro-sprinklers before and after the drip application. The highest 1,3-D and CP emission losses over a 2-wk monitoring period were from the control (36% 1,3-D and 30% CP) and HDPE tarp (43% 1,3-D and 17% CP) over shank injection. The pre-irrigation 4 d before fumigation and VIF tarp over shank injection had similar total emission losses (19% 1,3-D and 8-9% CP). The HDPE tarp and irrigations over subsurface drip-application treatments resulted in similar and the lowest emission losses (12-13% 1,3-D, and 2-3% CP). Lower fumigant concentrations in the soil-gas phase were observed with drip-application than in the shank-injection treatments; however, all treatments provided 100% kill to citrus nematodes in bags buried from 30 to 90 cm depth. Pre-irrigation and drip application seem to be effective to minimize emissions of 1,3-D and CP.


Though Alain Resnais' documentary film about the French National Library, All the World's Memory ( Toute la Memoir du Monde ), is meant to celebrate the library's scope and organization, anxiety seeps into its cinematic "language": dim black-and-white footage, a restlessly prowling camera, close-ups that cut off object from context and detail from whole, discontinuous cuts, choppy bullet-like comments, and darkly foreboding orchestral music. It's a beautiful film, but what does it say about Resnais' feelings about the library? Certainly awe, but also high modernism's anxiety about proliferating knowledge. "Man," the authoritative male voice-over proclaims, "fears being engulfed by this mass of words."


It is a late autumn day in Damascus, and I am back paying a visit to my friend 'Adil al-Zaki, owner of the Sham Dan cassette shop. Mr. Zaki's shop has "everything," including nearly half a million recordings in a variety of formats, mostly cassettes, of older Arab music and music from around the world. Zaki is a jocular octogenarian, somewhat round of belly and quick of smile, and a great enthusiast of Arab music-the "good music," as he would put it, and not the modern popular songs, for which he has little regard. Whenever I visited him I would generally sit for an hour or so while we listened to various artists-whomever he happened to be making a tape of at the time or others according to his mood: the great Egyptian artists Umm Kulthum and Muhammad 'Abd al-Wahhab, of course, but also Indonesian Qur'an readers, Persian oud players, all-women orchestras from Tunisia, and others, both famous and obscure. We'd sip little glasses of coffee, sit back in our chairs, and enjoy the music-as we did that autumn afternoon.


The research aims to study the provision of plant growth regulator (PGR) from banana weevil and shoots on the growth of oil palm seeds (Elaeis guineensis Jacq) in the main-nursery. The experiment was conducted in a greenhouse of Faculty of Agriculture, University of Riau in October 2013 to January 2014. Testing in the form an experiment using Completely Randomize Design (CRD) that consists of 3 treatment (without PGR, PGR of the bananas weevil: 75 ml and PGR of the bamboo sprout : 75 ml), every treatment repeated 4 times. Parameter that observed are high quality seeds, the number of leaves and the diameter weevil. Results of the study showed that the original PGR of bamboo sprout and bananas weevil influential was real increase seeds, the number of foot and mouth diameter weevil that without PGR. The original PGR of bamboo sprout increase each parameter higher than PGR of the bananas weevil.


Spatial predictions of near-surface air temperature ( T a i r ) in Antarctica are required as baseline information for a variety of research disciplines. Since the network of weather stations in Antarctica is sparse, remote sensing methods have large potential due to their capabilities and accessibility. Based on the MODIS land surface temperature (LST) data, T a i r at the exact time of satellite overpass was modelled at a spatial resolution of 1 km using data from 32 weather stations. The performance of a simple linear regression model to predict T a i r from LST was compared to the performance of three machine learning algorithms: Random Forest (RF), generalized boosted regression models (GBM) and Cubist. In addition to LST, auxiliary predictor variables were tested in these models. Their relevance was evaluated by a Cubist-based forward feature selection in conjunction with leave-one-station-out cross-validation to reduce the impact of spatial overfitting. GBM performed best to predict T a i r using LST and the month of the year as predictor variables. Using the trained model, T a i r could be estimated with a leave-one-station-out cross-validated R 2 of 0.71 and a RMSE of 10.51 ∘ C. However, the machine learning approaches only slightly outperformed the simple linear estimation of T a i r from LST ( R 2 of 0.64, RMSE of 11.02 ∘ C). Using the trained model allowed creating time series of T a i r over Antarctica for 2013. Extending the training data by including more years will allow developing time series of T a i r from 2000 on.


Ineffective aid management and coordination as well as old fashion model of aid sequencing were few of the major culprits why Bosnia and Herzegovina is still not on self sustainable path. Government representatives should eagerly embrace newest incentive related to increase in aid effectiveness-Paris Declaration. Commitments of Official Development Assistance in Bosnia and Herzegovina exceeded $ 7 billion from 1996 to 2004. We presented sectoral destination of aid funds and indicators of aid effectiveness. While aid driven post-conflict reconstruction has been relatively successful, insufficient structural reforms made BiH lagging behind most of the transition countries in the region. The most important achievements took place in the peace implementation activities which were necessary for ensuring reconciliation and a fertile ground for reconstruction and recovery. International support for establishment and maintenance of security exceeded $ 18 billion in the period 1996-2004. Further reforms, expected in near future, would not be possible in politically essentially divided country without promised the pot of gold that was held to come with EU membership.


This research work deals with the design and construction of an automatic triggered bell ringer circuit. Several previous attempts have been developed on intruder alert and a motion detection system, complex systems that operate excellently well. The automatic triggered bell ringer circuit integrates knowledge of these previous models and utilizes more readily available components. It also introduces the use of two sensors, thereby increasing its sensitivity. Major components used in the work are the Force and Light sensors, sensors that depict the concepts of pressure and light resistivity/conductivity respectively, and a laser beam directly projected permanently on the light sensor's surface. A force exerted on the Force sensor triggers a buzzer alarm and likewise, an obstruction in the path of the laser triggers the buzzer alarm. Once there is pressure exerted on the Force sensor, the resistance tends to infinity and voltage dropped across it biases the diode and transistor and the voltage reaching the buzzer triggers it. Likewise, the resistance of the light sensor tends to infinity when in darkness and the voltage dropped across it also biases a diode and transistor and triggers on the buzzer alarm. The work has been tested and seen to have a higher sensitivity, and is much cheaper than its counterparts. Keywords: Automatic Triggered Bell Ringer, Light Sensors, Light Dependent Resistor.


Alchemy is central to Jung's hypothesis of the collective unconscious. In this volume he begins with an outline of the process and aims of psychotherapy, and then moves on to work out the analogies between alchemy, Christian dogma and symbolism and his own understanding of the analytic process. Introducing the basic concepts of alchemy, Jung reminds us of the dual nature of alchemy, comprising both the chemical process and a parallel mystical component. He also discusses the seemingly deliberate mystification of the alchemists. Finally, in using the alchemical process as providing insights into individuation, Jung emphasises the importance of alchemy in relating to us the transcendent nature of the psyche.


Type analysis of Prolog is of primary importance for high-performance compilers, since type information may lead to better indexing and to sophisticated specializations of unification and built-in predicates to name a few. However, these optimizations often require a sophisticated type inference system capable of inferring disjunctive and recursive types and hence expensive in computation time.
The purpose of this paper is to describe a type analysis system for Prolog based on abstract interpretation and type graphs (i.e. disjunctive rational trees) with this functionality. The system (about 15,000 lines of C) consists of the combination of a generic fixpoint algorithm, a generic pattern domain, and a type graph domain. The main contribution of the paper is to show that this approach can be engineered to be practical for medium-sized programs without sacrificing accuracy. The main technical contributions to achieve this result are (1) a novel widening operator for type graphs which appears to be accurate and effective in keeping the sizes of the graphs, and hence the computation time, reasonably small; (2) the use of the generic pattern domain to obtain a compact representation of equality constraints between subterms and to factor out sure structural information.


Aims Dilated cardiomyopathy (DCM), a myocardial disorder that can result in progressive heart failure and arrhythmias, is defined by ventricular chamber enlargement and dilatation, and systolic dysfunction. Despite extensive research, the pathological mechanisms of DCM are unclear mainly due to numerous mutations in different gene families resulting in the same outcome—decreased ventricular function. Titin (TTN)—a giant protein, expressed in cardiac and skeletal muscles, is an important part of the sarcomere, and thus TTN mutations are the most common cause of adult DCM. To decipher the basis for the cardiac pathology in titin-mutated patients, we investigated the hypothesis that induced Pluripotent Stem Cell (iPSC)-derived cardiomyocytes (iPSC-CM) generated from patients, recapitulate the disease phenotype. The hypothesis was tested by 3 Aims: (1) Investigate key features of the excitation-contraction-coupling machinery; (2) Investigate the responsiveness to positive inotropic interventions; (3) Investigate the proteome profile of the AuP cardiomyocytes using mass-spectrometry (MS). Methods and results iPSC were generated from the patients' skin fibroblasts. The major findings were: (1) Sarcomeric organization analysis in mutated iPSC-CM showed defects in assembly and maintenance of sarcomeric structure. (2) Mutated iPSC-CM exhibited diminished inotropic and lusitropic responses to β-adrenergic stimulation with isoproterenol, increased [Ca2+]out and angiotensin-II. Additionally, mutated iPSC-CM displayed prolonged recovery in response to caffeine. These findings may result from defective or lack of interactions of the sarcomeric components with titin through its kinase domain which is absent in the mutated cells. Conclusions These findings show that the mutated cardiomyocytes from DCM patients recapitulate abnormalities of the inherited cardiomyopathies, expressed as blunted inotropic response.


In this letter, numerical simulation and experimental study of a radial-slab solid-state laser are presented. The laser includes four crossing-slabs pumped by four Xe flashlamps. The numerical simulation of coherent intensity in the near field and the far field indicates that the laser with the structure can improve the quality of output beam compared with incoherent beam combination. The radial-slab solid-state laser is fabricated, and initial experiments are carried out at a pulse repetition of 1 Hz. Nine beams in the near field and one combined beam in the far field are obtained in our initial experiment. The experimental results are consistent with the numerical analysis in the coherent condition. The results show that coherent beam combination is obtained by this laser.


A group of traders huddles around a pile of dried shark fins on a gleaming white floor in Hong Kong. A Papua New Guinean elder shoves off in his hand-carved canoe, ready to summon a shark with ancient magic. A scientist finds a rare shark in Indonesia and forges a deal with villagers so it and other species can survive. In this eye-opening adventure that spans the globe, Juliet Eilperin investigates the fascinating ways different individuals and cultures relate to the ocean's top predator. Along the way, she reminds us why, after millions of years, sharks remain among nature's most awe-inspiring creatures. From Belize to South Africa, from Shanghai to Bimini, we see that sharks are still the object of an obsession that may eventually lead to their extinction. This is why movie stars and professional athletes go shark hunting in Miami and why shark's fin soup remains a coveted status symbol in China. Yet we also see glimpses of how people and sharks can exist alongside one another: surfers tolerating their presence off Cape Town and ecotourists swimming with sharks that locals in the Yucatán no longer have to hunt. With a reporter's instinct for a good story and a scientist's curiosity, Eilperin offers us an up-close understanding of these extraordinary, mysterious creatures in the most entertaining and illuminating shark encounter you're likely to find outside a steel cage.... Download ebook, read file pdf Travels Through the Hidden World of Sharks


We want to create a scalable flash storage system that provides read/write separation and uses erasure coding to provide reliability without the storage cost of replication. Flash on Rails [19] is a system for enabling consistent performance in flash storage by physically separating reads from writes through redundancy. In principle, Rails supports erasure codes. However, it has only been evaluated using replication in small arrays, so it is currently uncertain how it would scale with erasure coding. In this work we consider the applicability of erasure coding in Rails, in a new system called eRails. We consider the effects of computation due to encoding/decoding on the raw performance, as well as its effect on performance consistency. We demonstrate that up to a certain number of drives the performance remains unaffected while the computation cost remains modest. After that point, the computational cost grows quickly due to coding itself making further scaling inefficient. To support an arbitrary number of drives we present a design allowing us to scale eRails by constructing overlapping erasure coding groups that preserve read/write separation. Finally, through benchmarks we demonstrate that eRails achieves read/write separation and consistent read performance under read/write workloads.


Visible transitions in the blue, green, and red of Pr3+ ions are of interest for laser applications. A description of spectroscopic properties of this rare earth ion in Zr–Ba–La–Al (ZBLA) fluorozirconate glass matrix is presented, using an original approach. Magnetic-dipole and electric-dipole contributions are calculated, in the context of the Judd–Ofelt theory, to determine the Ωt (t=2, 4, 6) parameters, lifetime, and branching ratios of P30 emitting level. Influence of overlapping transitions and sensitized transitions are discussed, as well as the use of the standard or normalized method. Branching ratios are measured using an experimental method and compared to theoretical ones. The influence of higher energy and thermally populated P31 and I16 levels on the P30 lifetime is also studied. Considering this influence, a good agreement is found between theoretical and experimental P30 lifetimes. Finally, emission cross sections are calculated for the visible transitions, using either the reciprocity method or the Fuchtbauer–Ladenburg formula, for different calculated Judd–Ofelt parameters, highlighting the ability of Pr3+-doped ZBLA to be used as a laser material.


We have previously identified a putative tumor suppressor gene, NISCH, whose promoter is methylated in lung tumor tissue as well as in plasma obtained from lung cancer patients. NISCH was observed to be more frequently methylated in smoker lung cancer patients than in non-smoker lung cancer patients. Here, we investigated the effect of tobacco smoke exposure on methylation of the NISCH gene. We tested methylation of NISCH after oral keratinocytes were exposed to mainstream and side stream cigarette smoke extract in culture. Methylation of the promoter region of the NISCH gene was also evaluated in plasma obtained from lifetime non-smokers and light smokers (< 20 pack/year), with and without lung tumors, and heavy smokers (20+ pack/year) without disease. Promoter methylation of NISCH was tested by quantitative fluorogenic real-time PCR in all samples. Promoter methylation of NISCH occurred after exposure to mainstream tobacco smoke as well as to side stream tobacco smoke in normal oral keratinocyte cell lines. NISCH methylation was also detected in 68% of high-risk, heavy smokers without detectable tumors. Interestingly, in light smokers, NISCH methylation was present in 69% of patients with lung cancer and absent in those without disease. Our pilot study indicates that tobacco smoke induces methylation changes in the NISCH gene promoter before any detectable cancer. Methylation of the NISCH gene was also found in lung cancer patients' plasma samples. After confirming these findings in longitudinally collected plasma samples from high-risk populations (such as heavy smokers), examining patients for hypermethylation of the NISCH gene may aid in identifying those who should undergo additional screening for lung cancer.


In this work, we propose a novel recurrent neural network (RNN) architecture. The proposed RNN, gated-feedback RNN (GF-RNN), extends the existing approach of stacking multiple recurrent layers by allowing and controlling signals flowing from upper recurrent layers to lower layers using a global gating unit for each pair of layers. The recurrent signals exchanged between layers are gated adaptively based on the previous hidden states and the current input. We evaluated the proposed GF-RNN with different types of recurrent units, such as tanh, long short-term memory and gated recurrent units, on the tasks of character-level language modeling and Python program evaluation. Our empirical evaluation of different RNN units, revealed that in both tasks, the GF-RNN outperforms the conventional approaches to build deep stacked RNNs. We suggest that the improvement arises because the GFRNN can adaptively assign different layers to different timescales and layer-to-layer interactions (including the top-down ones which are not usually present in a stacked RNN) by learning to gate these interactions.


The decision to build initiates the development process. After taking account of all the factors it represents a decision to embark on a built solution to satisfy the organisation's strategic objectives. It is a decision that senior managers and members of the design team should be aware of, reflect on and consider why the decision to build was made in the first place. By understanding the history of the strategic decision the design team may be better able to respond to client requirements and opportunities by providing the most appropriate building. In practice, most participants in the design process are often divorced from the decision within the client organisation and may lack the necessary background information that informed, guided or forced the choice of a building solution. There is a dearth of well‐documented material and literature on this key decision in the development process. The literature is sparse and that which does exist often ignores or only includes as a secondary issue the decision to build. The attitude is often one where the decision is generally accepted as a given, not to be revisited or amended by later players. Presents some key findings from the research into the project inception and the decision to build process, with particular emphasis on the environmental factors that influence the process and the product.


This paper introduces the semiparametric error correction model for estimation of export-import relationship as an alternative to the least squares approach. The intent is to demonstrate how semiparametric error correction model can be used to estimate the relationship between Ghana's export and import within the context of a generalized additive modelling (GAM) framework. The semiparametric results are compared to common parametric specification using the ordinary least squares regression. The results from the semiparametric and parametric error correction models (ECM) indicate that the error correction term and import variable are significant determinants of Ghana's exports. On the basis of Akaike Information Criteria and Generalized Cross-Validation (GCV) scores, it is found that the semiparametric error correction model provides a better fit than the widely used parametric error correction model for modeling Ghana's export-import relationship. The results of the analysis of variance provide further evidence of nonlinearity in Ghana's export and import relationship. In effect, this paper demonstrates the usefulness of semiparametric error correction model in the estimation of export – import relationship.


Expression of nitric oxide synthase followed by peroxidase activity makes Plasmodium visible to the insect's complement system. To complete their development in the mosquito, ookinetes—reproductive stages of the malaria parasite Plasmodium—must traverse the midgut epithelium and avoid being detected and lysed by the mosquito complement system (TEP1). Oliveira et al. identified mosquito heme peroxidase (HPX2) and NADPH oxidase 5 (NOX5) as key enzymes that are induced in midgut cells during ookinete invasion that, together with nitric oxide synthase, mediate protein nitration. The HPX2-NOX5 system potentiates nitric oxide (NO) toxicity and is critical for mosquitoes to mount an effective antiplasmodial response. Epithelial nitration and TEP1-mediated lysis appear to act sequentially in parasite killing, and epithelial nitration may help to promote the mosquito complement cascade. G. de Almeida Oliveira, J. Lieberman, C. Barillas-Mury, Epithelial nitration by a peroxidase/NOX5 system mediates mosquito antiplasmodial immunity. Science 335, 856–859 (2012). [Abstract] [Full Text]


Exposing additional topology information of networks to applications
and users beyond that of the current ALTO protocol can enable many
important existing and emerging use cases, and many network providers
already provide additional information about their networks. At the
same time, there is no standard for exposing network topology in a
manner that provides simplification via abstraction to the application
layer and information hiding via abstraction to the network provider.
In this document, we provide a survey of use-cases for extended
network topology information, present some initial requirements for
such services, and then give a framework of how to integrate such an
extended ALTO topology service with network control infrastructure.


Globally increasing energy demand, running short of fossil fuels and researches for finding environment friendly choices strengthen a solution of local electricity production, especially from renewable energy sources. In this type of systems, inverters play a key role by providing power transforms. Multilevel inverters can achieve very low total harmonic distortion (THD) values at low switching frequencies without using any filtering units when compared with classic two-level inverters. However, multilevel inverters use high number of semiconductor elements, which increases the probability of any fault in the circuit, which may cause the whole system stopping for a long time. This is very critical issue for the buildings that have vital importance like hospitals or the industries where faults cost large amounts of money. In this work, a Fault-tolerant cascaded H-Bridge quasi-eight-level multilevel inverter with a single DC source and with output-side transformers was designed and application of reconfiguration technique was shown. The proposed inverter system can continue working if a fault occurs in one of H-Bridges with a one-level decrement in the output voltage in quarter period.


This article presents an analytical approach to the reality of couples with children born in Spain who descend from at least one Romanian parent. It was carried out with the official data included in the Childbirth Statistical Bulletin of the National Statistics Institute. The Romanian community represents the largest contingent of foreign residents in Spain, showing a steady growth since 2000 to the present. For this reason, it is important to learn about the processes of settlement and integration of this population. Romanian immigrants in Spain are usually young people who also marry young people (especially if it's between people of the same nationality) and who reside mainly in Madrid, Valencia, Andalusia and Catalonia. The results show that Romanian-only couples reveal different patterns from couples with only one Romanian member.


The Cambrian Mount Simon Sandstone has been the subject of extensive study and multiple industrial-scale carbon storage demonstrations at Decatur, Illinois, USA. The development of a reliable paleoenvironmental model is critical to successful large-scale carbon dioxide (CO2) storage, but is complicated by the need to interpret pre-vegetation sedimentation processes. The present study presents a paleoenvironmental model of the Lower Mount Simon Sandstone, based on analysis of primary sedimentary structures in two cores and four complete high-resolution resistivity logs (FMI).
 The Lower Mount Simon Sandstone represents a vertical "drying-up" sequence composed of three associated depositional units: a north–south oriented coastal system at the base, an eastward-directed fluvial unit in the middle, and a westward-directed eolian system at the top that recycled medium- and fine-grained sand in the basin. Quantitative analysis of fluvial cross-strata indicates that the perennial river system was shallow (c. 1 m deep) with relatively narrow channel belts (c. 1 km). Adjacent sandy eolian-floodplain deposits contain abundant thin, crinkly planar laminae that are enriched in fines and are interpreted as cementation surfaces, likely of biological origin. Deflation lags and wind-ripple strata are commonly interbedded with the crinkly strata, suggesting that the recurrence of erosion and deposition that controlled sedimentary preservation on the floodplain were dominated by eolian transport, re-wetting, and (bio-) cementation. Such a prominent role of exposure to the wind, basin-scale sediment recycling, and eolian removal of fine-grained sediment would have ceased to exist for most climates after the development of vegetation on land, yet, may well be key to understanding the environmental context for early life on Earth.


We present optical and near-infrared (NIR) photometry for three gamma-ray burst supernovae (GRB-SNe): GRB 120729A, GRB 130215A / SN 2013ez and GRB 130831A / SN 2013fu. In the case of GRB 130215A / SN 2013ez, we also present optical spectroscopy at t − t0 = 16.1 d, which covers rest-frame 3000–6250 Å. Based on Fe ii λ5169 and Si ii λ6355, our spectrum indicates an unusually low expansion velocity of ∼4000–6350 km s−1, the lowest ever measured for a GRB-SN. Additionally, we determined the brightness and shape of each accompanying SN relative to a template supernova (SN 1998bw), which were used to estimate the amount of nickel produced via nucleosynthesis during each explosion. We find that our derived nickel masses are typical of other GRB-SNe, and greater than those of SNe Ibc that are not associated with GRBs. For GRB 130831A / SN 2013fu, we use our well-sampled R-band light curve (LC) to estimate the amount of ejecta mass and the kinetic energy of the SN, finding that these too are similar to other GRB-SNe. For GRB 130215A, we take advantage of contemporaneous optical/NIR observations to construct an optical/NIR bolometric LC of the afterglow. We fit the bolometric LC with the millisecond magnetar model of Zhang & Mészáros (2001), which considers dipole radiation as a source of energy injection to the forward shock powering the optical/NIR afterglow. Using this model we derive an initial spin period of P = 12 ms and a magnetic field of B = 1.1 × 1015 G, which are commensurate with those found for proposed magnetar central engines of other long-duration GRBs.


Malaria is the one of most important diseases in the world, especially in sub-Sahara Africa. This dissertation outlines the enormous burden of the disease in terms of social and economic costs in southern Africa. This dissertation assessed the range and quality of the cost-effectiveness of malaria prevention in sub-Sahara Africa. Six studies published from 1999 to 2003 are reviewed, covering insecticide treated nets, residual spraying, chemoprophylaxis for infants and environmental management. For infants, ITNs cost from US$ 2019 $2879 per death averted and cost $ III per DALY; chemoprophylaxis cost $ 4.1 per DALY and chemoprophylaxis plus iron cost $ 5.0 per DALY. For children, ITNs cost $ 1559 per death averted, $ 57 per DALY and $ 61 per sick child averted. For non-specific age group, ITNs cost $ 29 per infection averted, and RHS $ 9. Generally all interventions assessed are cost effective use of resources. The chemoprophylaxis is the least expensive malaria prevention among cost effective malaria prevention interventions, followed by residual spraying one round a year, residual spraying two rounds a year, insecticide treated nets with net treatment only and insecticide treated nets with net provision and treatment. There are operational, managerial and financial challenges faced these most cost-effective malaria interventions. Particularly, chemoprophylaxis is faced the tremendous drug resistance potential and is not being recommended to wide use; financial constraints and the potential delaying of children's immunity acquisition lowers the cost-effectiveness of insecticide treated nets; residual spraying is a relatively simpler, faster and cheaper method, but faces political and economic pressure of concerning environmental issues, especially the use of DDT. The integrated approach of environmental management plus residual spraying could be the most cost-effective method of malaria prevention with least adverse environment effects. However, policy makers should apply their knowledge to local conditions. Further, comprehensive education programmes are needed to gain support and understanding from local communities. This would raise the cost-effectiveness of all interventions.


Dear Editor, Hypertrophic osteoarthropathy (HOA) as a paraneoplastic disorder is most often associated with pulmonary malignancies1. Bone scintigraphy (BS) is known to be useful for detecting HOA1,2. Here, we present a lung cancer patient who demonstrated findings consistent with HOA on BS and somatostatin receptor scintigraphy (SRS). To the best of our knowledge, this is the first report of HOA visualized by SRS. A female aged 67 years, smoker (47 pack-years), presented with a 3-month history of generalized arthralgia, painful edema of the limps, and finger clubbing. BS using 99mTc-MDP demonstrated increased linear periosteal uptake in the long bones of the legs (Figure 1A), a characteristic scintigraphic pattern of HOA. A chest X-ray was done (given her history of smoking) and showed a mass in the right posterior hemithorax confirmed by computed tomography (CT) scan (Figure 2C). Further functional imaging with SRS using 99mTc-octreotide revealed that the pulmonary lesion was positive for somatostatin receptors (Figure 2D). Also, it showed mildly increased tracer uptake along the periosteum of both lower extremities (Figure 1B). Ultimately, histopathological examination revealed lung adenocarcinoma. ΗΟΑ, also named Marie–Bamberger syndrome was first described in the 1890s and is characterized clinically by periostitis of tubular bones, digital clubbing, and arthritic symptoms1. It can be classified as primary (very rare) or secondary (approximately 95% to 97% of cases). Secondary HOA is associated with a wide spectrum of diseases, including a variety of pulmonary disorders, also known as 'hypertrophic pulmonary osteoarthropathy' (e.g. primary and metastatic lung cancer, lung abscess, tuberculosis, sarcoidosis, emphysema, bronchiectasis, pulmonary fibrosis, and mesothelioma), cardiovascular disorders (e.g. cyanotic congenital heart disease, infective endocarditis), gastrointestinal disorders (inflammatory bowel disease and hepatic cirrhosis) and various other disorders. Secondary HOA is more frequently related to pulmonary malignancies (in up to 90%), especially lung cancer1. According to published reports, 4% to 32% of lung cancer patients develop HOA3. The clinical manifestations of HOA may precede the diagnosis of the underlying disease. BS is a sensitive imaging modality for evaluating a wide variety of skeletal disorders, including HOA1,2. This modality has higher sensitivity for detecting bone metastases in patients with lung cancer compared to SRS4,5. The exact mechanism of pathogenesis of HOA and clubbing remains unknown. Two models have been proposed: a neurogenic pathway and a humoral pathway. In the neurogenic pathway, diseased organs innervated by the vagus nerve induce a neural reflex leading to vasodilatation and increased blood flow to the extremities6. In the humoral pathway cytokines and growth factors (platelet-derived growth factor, prostaglandin E, and vascular endothelial growth factor) induce connective tissue and periosteal proliferation1. Our case report highlights the usefulness of BS in detecting HOA and the importance of additional (anatomical and functional) chest imaging in the evaluation of malignancy-related HOA. Additionally, this case report shows that SRS can identify HOA, which is a new addition to the literature regarding the range of potential scintigraphic imaging of this syndrome. Moreover, it lends credence to the therapeutic option of octreotide (a synthetic analogue of AFFILIATION 1 Department of Nuclear Medicine, Hippokration General Hospital, Thessaloniki, Greece 2 Department of Endocrinology, Diabetes and Metabolism, Elena Venizelou Hospital, Athens, Greece 3 Department of Nuclear Medicine, General Hospital of Thoracic Diseases Sotiria, Athens, Greece


This article aims to present a reflexion on some of the main reasons for companies to implement reverse logistics processes. Companies have difficulties in implementing reverse logistics as part of their business processes due to high cost of implementation and due to difficulties in measuring material returns. However, companies that have succeeded in implementing it have increased their competitiveness and improved their corporate image. This paper proposes six critical success factors for the implementation of reverse logistics: good income control, standardised and mapped processes, reduced time cycle, information systems, planned logistic grid and collaborative relations between customers and suppliers. Well-structured and implemented reverse logistics process brings up benefits and advantages to companies, beyond environmental ones.


This paper presents the potential application of ejector and the efficiency improvement it brings to powerplants that utilize low-temperature renewable and recoverable heat sources. The ejector significantly increases the efficiency of the organic Rankine cycle (ORC) by increasing the turbine temperature drop which is made possible by the expansion, mixing and recompression processes in the ejector. The driving fluid in the ejector of the modified cycle is the high-pressure liquid in the separator that is just circulated back to the evaporator in the ORC. Fundamental thermodynamic analysis of the novel ejector powerplant cycle was undertaken. Ammonia and propane, which are both natural working fluids, were used in the analysis. The analysis was limited by considering that the lowest pressure in the system must be higher than the atmospheric pressure to avoid vacuum leak. The calculation results showed that propane and ammonia can both give maximum efficiencies at different evaporator temperatures and fixed condenser temperatures in the range of 20 – 27%. At evaporator and condenser temperatures of 40°C and 30°C, respectively, ORC gives only 2.5% for the two working fluids while the ejector system gives 21.5% and 27.5% for ammonia and propane, respectively. The difference in efficiency reduces as the evaporator temperature increases.It has been shown that propane can give higher efficiencies and lower velocities in the ejector than ammonia at considerably lower evaporating temperatures, leading to more economical, safer and simpler design and operation. The ejector system with ammonia and propane as working fluids offers environment friendly power generation from low-temperature sources at improved efficiency. Keywords: Ejector, powerplant, propane, ammonia, organic Rankine cycle


Fruit and vegetables are an important component of a healthy diet and the main antioxidant suppliers in the human diet. Consumption of foods derived from fruits and vegetables is also essential; fruit juices, ciders, wines, and vinegars also contain significant amounts of polyphenolic compounds. The aim of the study was to determine the effect maceration of antioxidant activity and phenolic content of apple cider. Red delicious apples were used to produce natural apple cider with and without inclusion of maceration. Samples were taken from fresh red apple juice, macerated samples and apple cider. Apple cider (maceration was applied) (CAM) had the highest total phenolic content, chlorogenic acid, ORAC and TEAC levels. Chlorogenic acid was the dominant phenolic substance in apple juice and cider samples and chlorogenic acid was increased with maceration process.


Background. Preoperative anxiety complicates treatment and requires assessment by nurses in children. Children, with or without disability, are helped when pictures are used to support communication. The purpose of this pilot study was to test the reliability and validity of the modified short State-Trait Anxiety Inventory (STAI) using a modified Talking Mats method in children undergoing day surgeries. Method. A modified short STAI with pictorial support along the lines of the Talking Mats method was pre- and postoperatively administered to 42 typically developing children aged three to nine years. The parents assessed the children's anxiety, simultaneously and independently, by scoring the short STAI by proxy. Results. The modified short STAI showed moderate internal consistency and good construct validity in the age group seven to nine years. Conclusions. The results of this study support the use of the instrument for self-reports in children aged seven to nine years. Future research will explore the possibilities of also using this instrument for children with cognitive and communicative difficulties.


Part three in "Death or Glory" series, "Highroad to Hell" is Michael Asher's latest Second World War adventure. With Asher's insider knowledge of the SAS he brings to life the action of the battlefield in this fast-paced and compelling novel following Captain Tom Caine. Tunisia 1943 - the Allies' advance is halted by determined Axis forces. The 8th Army has no choice but to outflank the enemy along their impenetrable Mareth line in the hellish Matmata hills. On a mission to safeguard this movement, Captain Tom Caine's SAS patrol is diverted by a strange emergency signal that draws them to a derelict aircraft and a mysterious black box. Besieged by a Nazi Death's Head unit intent on retrieving the box and betrayed by a comrade who steals it, Caine must make a choice. Should he pursue the stolen object or stick to his original task and face almost certain death? The entire campaign rests on his decision. Michael Asher's third "Death or Glory" novel, "Highroad to Hell", will have you gripped to the very last page. Breathtaking bravery, astonishing feats of endurance, raids and battles described with terrific immediacy and pace. Compelling and definitive ...will surely not be bettered - "Sunday Telegraph" Detailed, scathingly honest. Asher has brought the critical eye of the knowledgeable insider to his in-depth study of SAS operations and personalities - Herald Michael Asher has served in the Parachute Regiment and the SAS. He is a fellow of the Royal Society of Literature, and has won the Ness Award of the Royal Geographical Society and the Mungo Park Medal of the Royal Scottish Geographical Society for Exploration. The first two books in this series, "The Last Commando" and "The Flaming Sword" were also published by Penguin.


Answer Set Programming (ASP) is a well-known declarative problem solving approach based on nonmonotonic logic programs, which has been successfully applied to a wide range of applications in artificial intelligence and beyond. To address the needs of modern applications, HEXprograms were introduced as an extension of ASP with external atoms for accessing information outside programs via an API style bi-directional interface mechanism. To evaluate such programs, conflict-driving learning algorithms for SAT and ASP solving have been extended in order to capture the semantics of external atoms. However, a drawback of the state-of-the-art approach is that external atoms are only evaluated under complete assignments (i.e., input to the external source) while in practice, their values often can be determined already based on partial assignments alone (i.e., from incomplete input to the external source). This prevents early backtracking in case of conflicts, and hinders more efficient evaluation of HEX-programs. We thus extend the notion of external atoms to allow for three-valued evaluation under partial assignments, while the two-valued semantics of the overall HEX-formalism remains unchanged. This paves the way for three enhancements: first, to evaluate external sources at any point during model search, which can trigger learning knowledge about the source behavior and/or early backtracking in the spirit of theory propagation in SAT modulo theories (SMT). Second, to optimize the knowledge learned in terms of so-called nogoods, which roughly speaking are impossible input-output configurations. Shrinking nogoods to their relevant input part leads to more effective search space pruning. And third, to make a necessary minimality check of candidate answer sets more efficient by exploiting early external evaluation calls. As this check usually accounts for a large share of the total runtime, optimization is here particularly important. We further present an experimental evaluation of an implementation of a novel HEX-algorithm that incorporates these enhancements using a benchmark suite. Our results demonstrate a clear efficiency gain over the state-of-the-art HEX-solver for the benchmarks, and provide insights regarding the most effective combinations of solver configurations.


This text, originated from my Master's thesis, aims to dissertate on genealogy as methodology, according to Michel Foucault's proposition. In this approach, the archeological analysis of the speech is understood as the foundation supporting genealogy by suggesting the description of the field as a net formed in the inter-relationship of the several knowledge present, which makes possible the discourse emerge according to our concept. The genealogical approach searches for the origin of the knowledge through the factors interfering in their emergence, maintenance and suitability to the discursive field, as elements included in a political speech opening the conditions to enable the individuals to be immersed in given discursive practices.


The heating of milk causes denaturation of the lactalbumin and lactoglobulin to an extent depending on both the temperature and the time of heating. A series of data has been given for the amounts of albumin and globulin denatured on heating samples of milk at various temperatures from 63 to 80° C, for periods of from 2½ to 60 min. An average of 10·4 per cent, of the total soluble protein was denatured after 30 min. heating at as low a temperature as 63° C. Smooth curves were obtained for the progress of denaturation with time at each temperature, and, over the range of 63–75° C, the relative increase in velocity of denaturation for each rise in temperature of 1° C. was found to be constant, the temperature coefficient of the reaction being 1·5.


In the logic of the Universons assumption, we deduce the nature of De Broglie wave and periodic mass variation for particles. We verify consistency with quantum mechanics, in particular the Schrodinger equation. We analyze the hypothesis that elementary particle mass is momentum circulating at light speed. We discover resonance rules acting within elementary particles leading to a formula governing the quantization of masses. Applying this formula to the electrons, muons, tauons and quarks, we find resonances that match with current measurements. We deduce the energy of unknown massless sub–particles at the core of electrons, muons, and tauons. Geometrical constraints inherent to our formula lead to a possible explanation to only three generations of particles. Based on particles geometry, we verify the consistency of the deduced quarks structure with QCD and raise the hypothesis that color charge is magnetic. We verify consistency with QCD symmetry and find that P and CP symmetry are broken by the interaction, in agreement with weak force knowledge. Our logic leads to re–interpret the Dirac condition on magnetic monopole charge, explain why the detection of magnetic monopoles is so difficult and, when detected, why magnetic charge can depart from Dirac prediction. We deduce a possible root cause of gravitation, resulting in the Schwarzschild metric and probable non existence of dark matter.


PURPOSE: This case study set out to explore a feedback intervention that incorporated team-generated scales created from best practice research principles from industrial / organizational psychology. METHOD: A college men's soccer team developed behaviorally-based anchored rating scales on 14 performance dimensions, and then provided self and team member ratings on each dimension. Each player received feedback on team average ratings about them relative to self-ratings. Player perceptions were assessed prior to scale development, prior to ratings, and after feedback was received. RESULTS: Findings indicate that the experience was challenging but positive; perceptions of potential and current ability changed significantly in opposite directions between ratings and feedback suggesting that players experienced a simultaneous improvement in motivation and reality check on their perceived potential. CONCLUSION: The data suggests that this feedback intervention may be a worthwhile endeavor to help motivate individuals and strengthen team cohesion. APPLICATIONS IN SPORT: In order to supplement a coach's feedback and unify teammate performance expectations, the creation and administration of behavior-based self and peer ratings may be a needed and viable option. If so, this case study offers a good model to attempt such an intervention.


BACKGROUND & AIMS
Liver inflammation and injury are mediated by the innate immune response, which is regulated by Toll-like receptors (TLR). Activation of TLR9 induces type I interferons (IFNs) via the interferon regulatory factor (IRF)-7. We investigated the roles of type I IFNs in TLR9-associated liver injury.

METHODS
Wild-type (WT), IRF7-deficient, and IFN-α/β receptor 1 (IFNAR1)-deficient mice were stimulated with TLR9 or TLR2 ligands. Findings from mice were verified in cultured hepatocytes and liver mononuclear cells (LMNCs) as well as in vivo experiments using recombinant type I IFN and interleukin-1 receptor antagonist (IL-1ra).

RESULTS
Type I IFNs were up-regulated during TLR9-associated liver injury in WT mice. IRF7- and IFNAR1-deficient mice, which have disruptions in type I IFN production or signaling, respectively, had increased liver damage and inflammation, decreased recruitment of dendritic cells, and increased production of tumor necrosis factor α by LMNCs. These findings indicate that type I IFNs have anti-inflammatory activities in liver. IL-1ra, which is produced by LMNCs and hepatocytes, is an IFN-regulated antagonist of the proinflammatory cytokine IL-1β; IRF7- and IFNAR1-deficient mice had decreased levels of IL-1ra compared with WT mice. IL-1ra protected cultured hepatocytes from IL-1β-mediated sensitization to cytotoxicity from tumor necrosis factor α. In vivo exposure to type I IFN, which induced IL-1ra, or administration of IL-1ra reduced TLR9-associated liver injury; the protective effect of type I IFNs therefore appears to be mediated by IFN-dependent induction of IL-1ra.

CONCLUSIONS
Type I IFNs have anti-inflammatory effects mediated by endogenous IL-1ra, which regulates the extent of TLR9-induced liver damage. Type I IFN signaling is therefore required for protection from immune-mediated liver injury.


The formation of complex subcellular organelles requires the coordinated targeting of multiple components. Melanosome biogenesis in mouse melanocytes is an excellent model system for studying the coordinated function of multiple gene products in intracellular trafficking. To begin to order events in melanosome biogenesis and distribution, we employed the classical coat‐color mutants ashen, dilute, and leaden, which affect melanosome distribution, but not melanin synthesis. The loci have been renamed Rab27a, Myo5a, and Mlph for their gene products. While each of the three loci has been shown to be required for melanosome distribution, the point(s) at which each acts is unknown. We have utilized primary melanocytes to examine the interdependencies between rab27a, myosin‐Va, and melanophilin. The localization of rab27a to melanosomes did not require the function of either myosin‐Va or melanophilin, but leaden function was required for the association of myosin‐Va with melanosomes. In leaden melanocytes permeabilized before fixation, myosin‐Va immunoreactivity was greatly attenuated, suggesting that myosin‐Va is free in the cytoplasm. Finally, we have complemented both the leaden and ashen phenotypes by cell fusion and observed redistribution of mature melanosomes in the absence of both protein and melanin synthesis. Together, our data suggest a model for the initial assembly of the machinery required for melanosome distribution.


Optimization of the design of railway infrastructure and its components requires a comprehensive understanding of the loading demands that are expected. Currently, many design guidelines for track components use historical wheel loads and calculate bending moments based on broad assumptions. However, tools are available to accurately quantify and characterize the variability each load has on a particular component. This is particularly important in shared use rail corridors where higher speed passenger services operate on the same infrastructure as heavy axle load (HAL) freight trains. Each traffic type generates unique demand variabilities, and these should be incorporated into a holistic approach to optimized track design. Therefore, researchers at the University of Illinois at Urbana-Champaign (UIUC) are conducting field research aimed at the characterization of field conditions on Amtrak's Northeast Corridor through the use of wheel impact load detector (WILD) data and concrete crosstie surface strain gauges. Results from this experimentation show high variability of loads resulting from varied types of train operations and significant differences in impact load ratios. Finally, laboratory measured flexural capacity for the concrete crossties showed a conservative design with a potential margin of improvement in reduction of residual capacity (i.e., factor of safety).


Balancing performance and safety is crucial to deploying autonomous vehicles in multi-agent environments. In particular, autonomous racing is a domain that penalizes safe but conservative policies, highlighting the need for robust, adaptive strategies. Current approaches either make simplifying assumptions about other agents or lack robust mechanisms for online adaptation. This work makes algorithmic contributions to both challenges. First, to generate a realistic, diverse set of opponents, we develop a novel method for self-play based on replica-exchange Markov chain Monte Carlo. Second, we propose a distributionally robust bandit optimization procedure that adaptively adjusts risk aversion relative to uncertainty in beliefs about opponents' behaviors. We rigorously quantify the tradeoffs in performance and robustness when approximating these computations in real-time motion-planning, and we demonstrate our methods experimentally on autonomous vehicles that achieve scaled speeds comparable to Formula One racecars.


Eukaryotic αβ-tubulin and bacterial FtsZ self-assemble into dynamic cytoskeletal polymers, microtubules or filaments, which are essential for chromosome segregation or bacterial cell division, respectively. Both share homologous core structures with guanosine-5'-triphosphate (GTP)-binding and GTPase-activating domains joined by a central helix, and form similar protofilaments with 4 nm spaced subunits along them. During assembly, the GTPase-activating domain of one subunit associates with the GTP binding domain of the preceding subunit, completing the active site. GTP hydrolysis triggers disassembly, which is coupled to free subunits switching into inactive conformation. Microtubule dynamics is inhibited by anticancer drugs binding near tubulin assembly interfaces. FtsZ is a target for new antibiotics discovery; several bacterial division inhibitors bind between FtsZ domains or at its GTP site. Other proteins in this superfamily include: gamma-tubulin that is essential for microtubule organisation; bacterial tubulin, a primitive structural homologue; and recently discovered TubZ, distant homologue employed by plasmids and phages for deoxyribonucleic acid positioning.

Key Concepts:

Tubulin superfamily proteins share a common fold within two domains that is different from other GTPases.

They assemble into microtubules and other different types of dynamic cytoskeletal filaments.

GTP hydrolysis is activated upon assembly and triggers disassembly.

Tubulin homologues spread among most organisms, where they are central to essential functions including DNA segregation or cell division.

They have important biomedical implications. Several effective antitumor drugs work by impairing microtubule dynamics. FtsZ is a target for new antibiotics.

Keywords:

protein self-assembly;
GTPases;
microtubules;
anticancer drugs;
bacterial cell division;
antibiotics


Deciding a protein's fate Protein synthesis inside cells is finely balanced with protein degradation to maintain homeostasis. Shao et al. show how differential affinities and binding kinetics of three chaperones regulate the fate of tail-anchored (TA) membrane proteins. The chaperone SGTA binds to TA proteins and quickly transfers them to the targeting factor TRC40 through the C-terminal domain of the quality-control module BAG6. Proteins that dissociate from SGTA can either rebind or, at a slower rate, be bound by the C-terminal domain of BAG6. The latter puts them on a path to degradation. This hierarchy means that biosynthesis has the higher priority, but excess free TA proteins are degraded. Science, this issue p. 298 Reconstitution of a protein triage pathway shows how relative binding affinities and kinetics regulate protein fate. Newly synthesized proteins are triaged between biosynthesis and degradation to maintain cellular homeostasis, but the decision-making mechanisms are unclear. We reconstituted the core reactions for membrane targeting and ubiquitination of nascent tail-anchored membrane proteins to understand how their fate is determined. The central six-component triage system is divided into an uncommitted client-SGTA complex, a self-sufficient targeting module, and an embedded but self-sufficient quality control module. Client-SGTA engagement of the targeting module induces rapid, private, and committed client transfer to TRC40 for successful biosynthesis. Commitment to ubiquitination is dictated primarily by comparatively slower client dissociation from SGTA and nonprivate capture by the BAG6 subunit of the quality control module. Our results provide a paradigm for how priority and time are encoded within a multichaperone triage system.


The efficiency of wave energy converters (WECs) is generally evaluated in terms of historical wave conditions that do not necessarily represent the conditions that those devices will encounter when put into operation. The main objective of the study is to assess the historical and near future efficiency and energy cost of two WECs (Aqua Buoy and Pelamis). A SWAN model was used to downscale the wave parameters along the NW coast of the Iberian Peninsula both for a historical period (1979–2005) and the near future (2026–2045) under the RCP 8.5 greenhouse scenario. The past and future efficiency of both WECs were computed in terms of two parameters that capture the relationship between sea states and the WEC power matrices: the load factor and the capture width. The wave power resource and the electric power capacity of both the WECs will decrease in the near future. The load factor for Aqua Buoy will decrease in the entire area, while it will remain unchanged for Pelamis in most of the area, except north of 43.5° N. The capture width and cost of energy will increase for both devices. The methodology here applied can be easily applied to any device and coastal domain under different climate change scenarios.