In this article, 20 years of data provide grounds for the analysis of private equity fund (PEF) performances. Gross returns for U.S. and Europe, the Middle East, and Africa (EMEA) PEFs are modeled and benchmarked with total market indexes (TMI) using an adjusted public market equivalent (PME+) – distributed to paid-in ratio (DPI) method. Average U.S. funds perform in line with benchmarks. Carried interest has no material impact on a PEF's relative performance to the index. Top-quartile funds exhibit an outperformance (net and gross basis). Timing of cash flows explains part of it. More than management fees, the level of the preferred return rate might reduce alignments of interests; calculating a spread with PME+ – DPI index and sharing the resulting alpha might increase it.


Abstract Mortgage foreclosures hit Detroit, Michigan hard between 2005 and 2014, especially in what we define as strong neighborhoods; there, more than one third of homes experienced foreclosure. Before the crisis hit, these selected tracts had largely intact physical environments and higher owner occupancy, household income and property value than the citywide median. In some of them residents worked intensely to abate the neighborhood effects of mortgage foreclosures. This study examines those efforts' effectiveness. We selected neighborhoods with the most extensive efforts, as measured, for instance, by creation of community-based plans and applications for grants, and we conducted interviews and field observations to examine those efforts. To assess strengthening of neighborhood housing markets, we applied a modified adjusted interrupted time-series approach to evaluate changes in prices as one measure of neighborhood change. We found that strong resident initiative supported by community development organizations and external assistance led to increased neighborhood housing prices, compared with comparable neighborhoods. However, when initiative, context, and support were weaker, community-based efforts could not prevent considerable decline.


ABSTRACT Covering the changes in Shakespeare editorial theory and practice over the decades between the publication of the Oxford Shakespeare (1986) and the New Oxford Shakespeare (2016), this article surveys a range of modern texts with different rationales and aimed at different readerships. The article has three sections: the imagery associated with editorial activity, issues of authorship and collaboration, and the place of performance in editions. We trace the conceptual changes between the Textual Companion that accompanied the 1986 edition, and the Authorship Companion that is the equivalent for the 2016 edition, discussing the role of quantitative and qualitative approaches to questions of authorship and collaboration. We pay particular attention to the metaphors and tropes that shape editorial discourse, finding their echoes in early modern paratextual material. Pervasive anthropomorphic textual imagery tends implicitly to feminize texts (and masculinize editors), and we discuss the changing demands on editors and the continued dominance of male editors, particularly for Shakespeare's tragedies and histories. A final section discusses Arden editorial generations of Hamlet alongside the play's own telos of interrupted succession and its preoccupation with ghosts and the past.


Plasma is a gas partially ionized which is considered the fourth state of matter. It consists of electrons, ions and neutrals in fundamental and excited states which make it a chemically active media. Within plasma, reactions (which are not allowed to take place in other media) can be achieved. In addition, depending on the way plasmas are created and their working power, low or very high temperatures can be generated. This wide temperature range enables many applications for plasmas technologies such as deposition of surface coatings, chemical analysis, nanomaterial synthesis, sterilization, food preservation? However, apart from these applications, plasma technology has been devoted to solve some environmental problems.
Global warming is one of the most worrisome problems that the scientific community should face up to. Global warming is related to the rise in the average temperature of Earth?s atmosphere and oceans which is caused by the increasing concentration of greenhouse gases produced by human activities such as the burning of fossil fuels. Plasma technology not only has been successfully utilized to eliminate some of the greenhouse gases or to destroy volatile organic waste, but also to generate hydrogen, which is considered as an alternative fuel to fossil ones.
Due to a decrease of fossil fuels reserves and the greenhouse effect, energy industry is devoting considerable resources and expertise to find other energy resources, and hydrogen is a promising option for the energy supply of fuel cells. Nevertheless, only two major technologies, which are catalytic route through the water gas shift reaction and electrolytic decomposition of water, have been developed at large scale. However, the use of catalysts involves some shortcomings due to some catalyst lifetime. Therefore, a more economic and environmental friendly alternative, such as plasma technology, is being researched to avoid some conventional hydrogen production drawbacks.
Recently, there has been a growing interest in using microwave plasmas sustained at atmospheric pressure to decompose alcohols or hydrocarbons as enriched-hydrogen sources. Their low-power operation requirements, high stability, reproducibility and non-thermal properties makes them suitable for this purpose. Microwave torches are noteworthy microwave plasma sources which are well-known thanks to their higher tolerance to sample injection and the possibility to deliver higher power amounts to the discharge in contrast to other microwave devices. TIAGO torch (Torche a Injection Axiale sur Guide D?Ondes) [1] has been developed as an improvement of the well-studied TIA torch (Torche a Injection Axiale) [2]. All these characteristics jointly to atmospheric pressure conditions make TIAGO torch an excellent candidate to industrial implementation.
Notwithstanding Prof. M. Moisan and co-workers published in 2001 the design of TIAGO torch [1], no research concerning the kind of plasmas produced by it or its use in applications has been carried out. Thus the essential aim of the present Thesis has been the study of plasmas sustained with TIAGO torch and their use application for solving some environmental issues. For this reason, in the present work, both basic and practical researches have been joined. On one hand, a complete characterization of plasmas produced by the TIAGO torch (fundamental research) was necessary prior to exploring its application capabilities. On the other hand, from the knowledge extracted in the first step of this research, the production of hydrogen from ethanol decomposition was developed (applied research). Hence, the objectives pursued in this Thesis have been: To identify the experimental conditions (flows and input powers used to sustain the discharge) needed to keep the discharge stable and to describe the morphology, kinetics and thermodynamic equilibrium degree of the Ar discharges generated with TIAGO torch.
To assess the capability of Ar plasmas to decompose ethanol molecules introduced into the discharge and to study the amount of hydrogen generated in the decomposition process as well as to identify other gases produced in the gas exhaust.


We present the preparation and Cu(II) adsorption characteristics of a new and innovative composite which was composed of a carboxymethylated polyethyleneimine (CM-PEI) and an activated carbon with a nanopore less than 2 nm in diameter. In this study, we examined the adsorption phenomena of Cu(II) on the CM-PEI/F400 composite and evaluated the adsorption data using three kinds of isotherm models (Langmuir, Freundlich, and Temkin isotherms). It was found that the adsorption of Cu(II) on the CM-PEI/F400 composite obeys the Langmuir isotherm model. Furthermore, The Cu element mapping results showed that Cu was well distributed throughout all the surface of the composite particle, suggesting that the surface of the F400 particle was uniformly covered with CM-PEI.


Much of our contemporary discussion of human rights activism in rapidly changing or "developing" societies is dominated by a rule of law perspective, from which rights activism and cause lawyering are viewed as subservient to rule of law reform goals. Examining the conflicting attitudes of different Chinese human rights lawyers to their work, I suggest that attention should be paid to a radically different perspective, taken by some of those actually engaged in activism. The practice of caution and self-restraint, arising from awareness of the potentially dangerous consequences of rights activism, may appear to be the only sensible attitude in the current Chinese context, and is justified in part by the need to make "constructive" contributions to the rule of law. But the lawyer whose actions are discussed here was unwilling, for what is suggested are fully justified reasons, to practice such caution, as he acted to help those most in need of defense of their rights. The attitude of lawyers and activists like him accentuates the deep contradictions in China's current legal and political system. Their experience indicates the limits of possible reform.


This paper presents an analytical method for calculating the effect of winding harmonics on the asynchronous torque of a single-phase line-start permanent-magnet motor. The method is an extension of earlier work, which combines symmetrical-component analysis with d-q-axes theory to model the various components of forward and backward rotating fields. The effect of individual winding harmonics is brought out both theoretically and experimentally by comparing the calculated and measured torque/speed characteristics for a series of six motors with different distributions of turns in both main and auxiliary windings


In the twenty-teens, there are increasing numbers of women occupying executive positions in politics, business and the law but their words and actions rarely make the front page. In this article, we draw on data collected as part of the 2015 Global Media Monitoring Project (GMMP) and focus on England, Scotland, Wales and the Republic of Ireland. Since the first GMMP in 1995, there has been a slow but steady rise in the proportion of women who feature, report or present the news (now at 24 per cent), but that increase is a mere 7 per cent over 20 years. Not only is there a problem with visibility but our data also suggest that when women are present, their contributions are often confined to the realm of the private as they speak as citizens rather than experts and in stories about health but not politics. Just over a third of the media professionals we coded were women and older women are almost entirely missing from the media scene. Citizens and democracy more generally are poorly served by a news media which privileges men's voices, actions and views over the other 51 per cent of the population: we surely deserve better.


C.d. spectroscopy was used to investigate the structures of Ca2+-ATPase (Ca2+-transporting ATPase) in the E1 and E2 states in native, in fluorescein isothiocyanate (FITC)-labelled and in solubilized sarcoplasmic reticulum (SR) preparations. The E1 state was stabilized by 100 microM-Ca2+ and the E2 state by 0.5 mM-Na3 VO4 and 0.1 mM-EGTA. There were no significant differences detected in the c.d. spectra and the calculated secondary structures between the E1 and E2 states in any of the three types of preparations. The FITC-labelled SR did show the characteristic changes in FITC fluorescence on addition of Ca2+ or vanadate, indicating that the preparation was competent for E1----E2 transitions. Therefore the absence of changes in the c.d. spectra implies that the E1----E2 transition in the Ca2+-ATPase does not involve a major net rearrangement of the polypeptide backbone conformation.


Introduction: Galectin-3 (Gal-3) expression act as a potential novel therapeutic strategy in the treatment of a broad range of inflammatory diseases. Aim: This study aims to study the cross-talk between macrophage and adipocyte cells with Gal-3 upon lipopolysaccharides (LPSs) challenge. Materials and Methods: Cytokine secretion in 3T3-L1 adipocyte-RAW 264.7 macrophage cells were greatly enhanced on LPS stimulation compared to isolated cell culture system, suggesting the cross-talk between these cell types during LPS exposure. Gene and protein expression profile was analyzed by reverse transcription-polymerase chain reaction for understanding the inflammatory responses. Results: Decreased expression of interleukin 6 was confirmed as lowered suppressor of cytokine signaling 3 expressions downstream. A critical appraisal of the role of nuclear factor-κB (NF-κB) in LPS induced alteration of inflammatory phenotype was confirmed as decreased formation of tumor necrosis factor-α transcript using specific inhibitors of NF-κB, along with LPS treatment. Further, Gal-3 also inhibited nuclear p65 translocation, IkB-α degradation and induction of inducible nitric oxide synthase, in response to LPS. Conclusion: These results clearly suggest decreased oxidative burden and inflammation are significantly affected by Gal-3.


The hand is an organ of grasping as well as sensation, communication, and fine dexterity. Since the 80's, many researchers have been attempting to develop robotic devices aiming at replicating the functions of the human hand in the fields of industrial robotics, tele-manipulation, humanoid robotics, and upper limb prosthetics. A special kind of robotic hand is the hand exoskeleton, that is directly attached to the human hand with the aim of providing assistance in motion/power generation. Hand exoskeletons are increasingly widespread in robot-based rehabilitation of patients suffering from different pathologies (in particular neurological diseases). This paper reviews the state-of-the-art of hand exoskeletons developed for rehabilitation purposes and proposes a new systematic classification according to three key points related to the kinematic architecture: (i) mobility of a single finger exoskeleton, (ii) number of physical connections between the exoskeleton and the human finger phalanges, and (iii) way of integration of the exoskeleton mechanism with the human parts. The discussion based upon the classification can be helpful to understand the reasons of adopting certain solutions for specific applications and the advantages and drawbacks of different designs, based on the work already done by other researchers. The final purpose of the proposed classification is then to provide guidelines useful for the design of new hand exoskeletons on the basis of a systematic analysis. As an example, the solution designed, manufactured and clinically tested by the authors is reported.


Nitrogen fixation by blue-green algae in highly eutrophic Clear Lake, California, was severely inhibited by trace amounts of copper. The chelation capacity of the lake is probably saturated by indigenous copper. Additions were only 1/200 of those normally used in algal control. Since nitrogen fixation provides half of the lake's annual nitrogen budget, economical eutrophication control appears possible.


UAV (Unmanned Airborne Vehicle) high resolution digital image acquisition systems based on small format cameras provide a versatile alternative to the solution of environmental monitoring and remote sensing problems. Through digital image processing these small format optical and multi-spectral camera images can obtain orthomosaics that meet quality standards at a fraction of the cost of traditional heavier manned vehicle equipment. They also have higher availability, resolution and flexibility can also be obtained when compared to satellite images. This paper presents research and development undertaken to produce a computational system that can automatically process optical and multi-spectral images obtained from digital cameras mounted on a UAV aircraft. The system acquires, rectifies, mosaics and georeferences these images with minimum operator assistance. Results prove that the process can almost be fully automated and that the system can be operated by minimally trained personnel. Processed images obtained by the software can be used for pattern recognition, photo interpretation, photogrammetry, and other remote sensing applications.


Through a series of 9 artistic etchings, the author's feelings of her experience with immobility due to trauma naturally fell into 3 groups of 3. These groupings represent the natural organization of human experience and all stories-the beginning, the middle, and the end. Here, the author and artist shares an account of her healing journey that revealed itself through artistic expression.


Objectives The aim of our study is to validate and complement recently reported epigenetic biomarkers of exposure to tobacco smoke based on data from two cohorts and to characterise their prospective nature. Method We used case-control data from studies nested in two prospective cohorts: the Italian component of the European Prospective Investigation into Cancer and Nutrition study (N = 620) and the Norwegian Women and Cancer study (N = 382) as a validation dataset. For each of the participant, genome wide methylation profiles were acquired from blood samples collected at enrolment using the Illumina HM450 DNA methylation array. We performed epigenome wide association studies within each dataset to assess the relation between methylation levels and smoking-related variables, controlling for technical variation (batch effects) and confounding factors (including white blood cell composition). Results We found 8 and 897 CpG sites differentially methylated in former and current smokers, while compared to never smokers, respectively. The 8 candidate markers of former smoking showed a gradual reversion of their methylation levels from those typical of current smokers to those of never smokers. Further analyses using cumulative (over varying time windows) smoking intensities, highlighted three classes of biomarkers: short and long term biomarkers (measuring the effect of smoking in the past 10, and in the past 10 to 30 years respectively), and lifelong biomarkers detected more than 30 years after quitting smoking. Conclusions Genome-wide DNA methylation profiles show promising abilities to detect short-term to lifelong biomarkers of tobacco smoke exposure and, more generally, to potentially identify time-varying biomarkers of exposure.


Escherichia coli isocitrate lyase was inactivated by iodacetate in a pseudo-first-order process. Complete inactivation was associated with the incorporation of only one carboxymethyl group per enzyme subunit. The substrate and products of the enzyme protected against inactivation, suggesting that the reactive group may be located at the active site. Isolation and sequencing of a carboxymethylated peptide showed that the modified residue was a cysteine, in the sequence Cys-Gly-His-Met-Gly-Gly-Lys. The reactivity of isocitrate lyase to iodoacetate declined with pH, following a titration curve for a group of pKa 7.1. The Km of the enzyme for isocritrate declined over the same pH range.


New data from upper Miocene deposits in the Madre de Dios region, southern Peru, allow the delineation of tidal regime for the first time in western Amazonia and provide strong evidence of elevated tidal range and brackish-water influence. The results point out the insufficiency of the current depositional models and support the earlier hypothesis that western Amazonia was also connected to the Paranan Sea during the late Miocene. In this paper we present sedimentological, ichnological, and statistical (Fourier transformation) data from two selected outcrops containing rhythmite successions from an area that is traditionally considered as continental. The sediments are interpreted to represent tide-dominated, inner-middle estuarine deposits. The cyclic rhythmites display semidiurnal cyclicity. The results are significant because (1) they contradict recent interpretations of the area's paleoenvironmental history; (2) the evidence for tidal processes is persuasive; and (3) the delineated tidal regime and range provide a unique insight into the depositional dynamics of a system having many important paleogeographic implications.


Assembly and modulation of focal adhesions during dynamic adhesive processes are poorly understood. We describe here the use of ventral plasma membranes from adherent fibroblasts to explore mechanisms regulating integrin distribution and function in a system that preserves the integration of these receptors into the plasma membrane. We find that partial disruption of the cellular organization responsible for the maintenance of organized adhesive sites allows modulation of integrin distribution by divalent cations. High Ca2+ concentrations induce quasi-reversible diffusion of beta1 integrins out of focal adhesions, whereas low Ca2+ concentrations induce irreversible recruitment of beta1 receptors along extracellular matrix fibrils, as shown by immunofluorescence and electron microscopy. Both effects are independent from the presence of actin stress fibers in this system. Experiments with cells expressing truncated beta1 receptors show that the cytoplasmic portion of beta1 is required for low Ca2+-induced recruitment of the receptors to matrix fibrils. Analysis with function-modulating antibodies indicates that divalent cation-mediated receptor distribution within the membrane correlates with changes in the functional state of the receptors. Moreover, reconstitution experiments show that purified alpha-actinin colocalizes and redistributes with beta1 receptors on ventral plasma membranes depleted of actin, implicating binding of alpha-actinin to the receptors. Finally, we found that recruitment of exogenous actin is specifically restricted to focal adhesions under conditions in which new actin polymerization is inhibited. Our data show that the described system can be exploited to investigate the mechanisms of integrin function in an experimental setup that permits receptor redistribution. The possibility to uncouple, under cell-free conditions, events involved in focal adhesion and actin cytoskeleton assembly should facilitate the comprehension of the underlying molecular mechanisms.


Many structured prediction problems (particularly in vision and language domains) are ambiguous, with multiple outputs being correct for an input - e.g. there are many ways of describing an image, multiple ways of translating a sentence; however, exhaustively annotating the applicability of all possible outputs is intractable due to exponentially large output spaces (e.g. all English sentences). In practice, these problems are cast as multi-class prediction, with the likelihood of only a sparse set of annotations being maximized - unfortunately penalizing for placing beliefs on plausible but unannotated outputs. We make and test the following hypothesis - for a given input, the annotations of its neighbors may serve as an additional supervisory signal. Specifically, we propose an objective that transfers supervision from neighboring examples. We first study the properties of our developed method in a controlled toy setup before reporting results on multi-label classification and two image-grounded sequence modeling tasks - captioning and question generation. We evaluate using standard task-specific metrics and measures of output diversity, finding consistent improvements over standard maximum likelihood training and other baselines.


The use of fee competition by construction industry clients has increased the need for design consultants to predict more accurately the cost of their professional services. There is evidence of concern among clients that fee reductions resulting from fee competition have been accompanied in many cases by a reduction in the level of services provided by consultants. However, there is little published work on design cost estimation methods and their accuracy. This paper describes a recently completed programme of research in design cost estimation practice in the United Kingdom. An overview of design cost estimation practice is presented and the development and operation of a model which simulates the design cost estimation process is described. The paper explains and presents the results of a data collection strategy that was adopted to provide input for the model and conclusions are drawn on the validity of the model when compared to the indicative levels of accuracy in design cost estimation suggested in the literature. Finally, recommendations are given for future research work that should lead to a usable cost estimation tool for design consultants.


Author(s): Capone-Newton, Peter | Advisor(s): Ong, Paul M | Abstract: Using the Los Angeles Family and Neighborhood Survey (L.A. FANS), detailed individual-level data on shopping location, store name, and body mass index are analyzed to assess relationships between body mass index and food store types. The analysis groups similar store brands to create unique food store types, providing finer discrimination than industrial classification or annual sales volume. Seven food store types are created: English-language major supermarket chains, discount food stores with "less", "save", or "bargain" in the name, Spanish-language name supermarkets or grocery stores, specialty stores defined as having fewer locations, smaller format, specific product focus, and/or limited product inventory, and independent, small, and bulk food stores. Documentation within the dataset of shopping locations, home locations, and car ownership allow strict control for distance and transportation. Accounting for these and other individual and neighborhood characteristics using multivariate regression models, body mass index is significantly lower in people who shop in specialty and Spanish-language name food store types compared to major chain food store types in higher poverty neighborhoods. Additional analysis indicates that reported supermarket shopping rates are higher than expected based on the prevalence of supermarkets in home Census tracts. Absence of neighborhood supermarkets (in home Census tracts) is a common state among respondents across all poverty strata, although more common in very poor tracts. In a subgroup of non-movers over a six-year period, opening and closing of stores is associated with change in shopped store type. Because the main results are cross-sectional, causal inference is difficult. Store types may influence body mass index, or individuals may have unobserved characteristics, which explain the association between store types and body mass index. Further research is needed to assess the direction of association. However, these results suggest specific store types should be the focus of policy and research rather than broader categories defined by sales volume or industrial classification. Absence of supermarkets may be an insufficient tool to characterize shopping behavior. Store opening and closing may stimulate change in store type preferences, but whether this change in store type is associated with change in health behaviors or health outcomes is unknown.


This paper traces briefly the history of the development of the AD.7092 series of automatic radio direction finders and describes the special features of the AD.7092C which was designed to suit the requirements of North American operators. Novel features include an electrical remote control system and a tuned remote sense amplifier which permits the use of long feeders using small sense antennas. The suppressed loop antenna and method of error compensation are described and the trend of future ADF developments in Great Britain is indicated.


The heat shock cognate protein HSP73 (or HSC70) is a member of the HSP70 multigene family. This protein has several functions, including binding to nascent polypeptides to facilitate correct folding and the uncoating of clathrin-coated vesicles. Analysis of somatic cell hybrids by two-dimensional protein gel electrophoresis revealed the presence of a 73-kDa protein in two hybrids containing human chromosomes 5, 6, 9, and 11 in common. Using Western blot analysis, we demonstrate that this protein is a member of the HSP70 family and, by Southern blot analysis, that the HSP73 gene is located on human chromosome 11. Fluorescence in situ hybridization further localized HSP73 to the region 11q23.3-q25. This region is involved in a number of genetic rearrangements and is associated with several well-characterized tumours.


This guide is intended to help students get started writing papers. Topics covered include selecting a research topic, where to search, how to evaluate information, how to get organized and start writing, and tips on copyright and plagiarism.


A set of centralized burst-level cell scheduling schemes, namely, First Come First Served with Frame Reservation (FCFS-FR), FCFR-FR+, Earliest Deadline First with Frame Reservation (EDF-FR), EDF-FR+, and Multitraffic Dynamic Reservation (MTDR), are investigated for transmission of multiservice traffic over time division multiple access (TDMA)/time division duplex (TDD) channels in wireless ATM (WATM) networks. In these schemes, the number of time slots allocated to a virtual circuit (VC) during a frame-time is changed dynamically depending on the traffic type, system traffic load, the time of arrival (TOA)/time of expiry (TOE) value of the data burst and data burst length. The performances of these schemes are evaluated by computer simulation for realistic voice, video and data traffic models and their quality-of-service (QoS) requirements in a wireless mobile multimedia network. Both the error-free and the correlated fading channel conditions are considered. Simulation results show that the EDF-FR+ and MTDR schemes outperform the other schemes and can provide high channel utilization with predictive QoS guarantee in a multiservice traffic environment even in the presence of bursty channel errors. The EDF-FR+ scheme is found to provide better cell multiplexing performance than the MTDR scheme, Such a scheme would be easy to implement and would also result in a power conservative TDMA/TDD medium access control (MAC) protocol for broadband wireless access. Burst-level cell scheduling schemes such as EDF-FR+ can be easily adapted as MAC protocols in the emerging differentiated services (DS) enhanced wireless Internet protocol (IP) networks.


The European Parliament started its new term with three empty seats. The Catalan politicians Carles Puigdemont, Antoni Comín and Oriol Junqueras got elected in the European Parliamentary elections of 26 May 2019 but the Spanish Central Electoral Commission did not include their names in the list which was notified to the European Parliament on 17 June 2019. The reason is that that they did not appear in person to swear or affirm allegiance to the Spanish Constitution, which is a formal requirement under the Spanish election legislation. The President of the EU General Court dismissed an application of Carles Puigdemont and Antoni Comín for interim measures by referring to the Spanish electoral law. Thereby, however, he completely ignored the EU citizenship dimension of the case.


Making multiplexed subcellular protein maps Being able to visualize protein localizations within cells and tissues by means of immuno-fluorescence microscopy has been key to developments in cell biology and beyond. Gut et al. present a high-throughput method that achieves the detection of more than 40 different proteins in biological samples across multiple spatial scales. This allows the simultaneous quantification of their expression levels in thousands of single cells; captures their detailed subcellular distribution to various compartments, organelles, and cellular structures within each of these single cells; and places all this information within a multicellular context. Such a scale-crossing dataset empowers artificial intelligence–based computer vision algorithms to achieve a comprehensive profiling of intracellular protein maps to measure their responses to different multicellular, cellular, and pharmacological contexts, and to reveal new cellular states. Science, this issue p. eaar7042 Multiplexed (40-plex) indirect immunofluorescence quantifies subcellular protein organization on cellular and multicellular scales. INTRODUCTION Obtaining multiplexed molecular readouts from large numbers of single cells in situ is an important technological goal to facilitate scientific discoveries in basic and translational research. Various methods have been developed in recent years to achieve spatially resolved multiplexed measurements of the abundance of large sets of mRNAs or proteins in biological samples. These technologies have brought the promise that, through large-scale efforts, all functionally relevant cell types of an organism will emerge from such multiplexed data in an unbiased manner. Furthermore, these cell types will be able to be mapped within their physical context within a tissue. RATIONALE The involvement of an mRNA or protein (state) in cellular function depends on its specific intracellular location and interaction with other molecules and cellular structures. Moreover, the phenotype of an individual cell is determined by the functional state, abundance, morphology, and turnover of its organelles and cytoskeletal structures. To functionally interpret molecular multiplexed information, such measurements will thus need to resolve the intracellular length scale. RESULTS We report a simple, robust, and nondegrading protocol that achieves 40-plex protein staining in the same biological sample using off-the-shelf antibodies called iterative indirect immunofluorescence imaging (4i). In conjunction with high-throughput automated microscopy and computer vision, 4i allows highly reproducible multiplexed measurements from surface areas of several mm2 subsampled by pixels of 165 nm by 165 nm. This approach simultaneously captures functionally relevant properties that emerge at the cell population, cellular, and intracellular level. 4i can thus quantify the influence of local cell crowding on protein abundance, the effect of cell cycle position on protein phosphorylation, patterns of protein subcompartmentalization, and organelle morphology all in the same single cell and across thousands of cells. We developed a data-driven computer vision approach that generates multiplexed protein maps (MPMs). MPMs comprehensively quantify intracellular protein composition with high spatial detail in large numbers of single cells. They are not confounded by the specific relative geometry and orientation of an individual cell. Thus, MPMs allow systematic comparisons of subcellular spatial protein distribution between single cells that experience different cell cycle states, microenvironments, growth conditions, or exposure to drugs. Using the example of subcellular relocalization of epidermal growth factor (EGF) receptor upon exposure to EGF, we demonstrate that MPMs allow the systematic definition of cellular states undetectable by multiplexed whole-cell measurements. The findings are functionally relevant and can be connected to multiple molecular and phenotypic properties apparent at the cellular and cell population scale. CONCLUSION By preventing photocrosslinking during imaging, 4i enables multiplexed immunofluorescence with off-the-shelf antibodies, both in small-scale and high-throughput experiments. 4i datasets cover multiple length scales, eliminating the need for extrapolation or inference in the interpretation of results. Integration of these length scales in one dataset reveals a richness of scale-crossing connections that current models of biological processes do not yet consider. These connections determine how gene expression is adapted to the cellular state, how a cell type is determined, how a pathological cellular phenotype emerges, or how a tumor cell responds to a drug. Iterative indirect immunofluorescence imaging (4i). 4i obtains 40-plexed protein readouts at high spatial detail in thousands of cells with the use of off-the-shelf antibodies. Multiplexed protein maps derived from such images provide a comprehensive quantitative description of compartmentalized intracellular protein composition. These maps can identify new cellular states and allow quantitative comparisons of intracellular organization between single cells in different cell cycle states, microenvironments, and drug treatments. Obtaining highly multiplexed protein measurements across multiple length scales has enormous potential for biomedicine. Here, we measured, by iterative indirect immunofluorescence imaging (4i), 40-plex protein readouts from biological samples at high-throughput from the millimeter to the nanometer scale. This approach simultaneously captures properties apparent at the population, cellular, and subcellular levels, including microenvironment, cell shape, and cell cycle state. It also captures the detailed morphology of organelles, cytoskeletal structures, nuclear subcompartments, and the fate of signaling receptors in thousands of single cells in situ. We used computer vision and systems biology approaches to achieve unsupervised comprehensive quantification of protein subcompartmentalization within various multicellular, cellular, and pharmacological contexts. Thus, highly multiplexed subcellular protein maps can be used to identify functionally relevant single-cell states.


Plastic deformation of polypropylene (PP) resulting from equal channel angular extrusion (ECAE) process was investigated in a 135° die. A phenomenological elastic-viscoplastic constitutive model was identified and coupled with the three-dimensional finite element (FE) method in order to predict the different processing parameters governing the deformation behaviour of PP during the extrusion. An optimal agreement between FE results and experimental data was obtained for a friction coefficient of 0.2. A detailed three-dimensional FE analysis of stress-strain field distribution was then carried out. The effects of both the number of extrusion passes and the processing routes were experimentally highlighted. The results show that the pressing force decreases with the increase of the number of extrusion passes and reaches its saturation state rapidly for routes A and C while, for routes BA and BC, it requires a high number of passes.


High Q-values of spiral inductors at frequency around 5/spl sim/6 GHz have been achieved with a multilayer spiral (MLS) structure on a high loss silicon substrate. Compared to a one-layer spiral (OLS) inductor, the Q-value of a 4-nH inductor has been improved by about 80% at 5.65 GHz. The impact of the structure on Q-value and resonant frequency has been analyzed, which shows that an optimal height for the via of MLS inductors should be considered when inductors are designed. The fabrication process is compatible with Cu/SiO/sub 2/ interconnect technology.


Vehicular communication (VC) systems have the potential to improve road safety and driving comfort. Nevertheless, securing the operation is a prerequisite for deployment. So far, the security of VC applications has mostly drawn the attention of research efforts, while comprehensive solutions to protect the network operation have not been developed. In this paper, we address this problem: we provide a scheme that secures geographic position-based routing, which has been widely accepted as the appropriate one for VC. Moreover, we focus on the scheme currently chosen and evaluated in the Car2Car Communication Consortium (C2C-CC). We integrate security mechanisms to protect the position-based routing functionality and services (beaconing, multi-hop forwarding, and geo-location discovery), and enhance the network robustness. We propose defense mechanisms, relying both on cryptographic primitives and plausibility checks mitigating false position injection. Our implementation and initial measurements show that the security overhead is low and the proposed scheme deployable.


In response to the recent increase in FDA-approved specialty drugs and escalating specialty drug prices, drug companies now offer patient support programs ("PSPs") for eligible patients prescribed a particular pharmaceutical drug. Such programs encompass both financial assistance for the purchase of a specialty drug and behavioral services, including nursing support and injection training, intended to improve drug adherence. Although ostensibly gratuitous, these programs have a steep and underappreciated cost: disclosure of protected health information. In effect, patient support programs compel patients to trade protected health information for drug access. This Article provides the first in- depth examination of the legal and ethical concerns associated with patient support programs. Enrollment in a drug company's patient support program furnishes the company with linked patient- and prescriber- identifying information for each enrollee, data which may enable drug companies to target marketing to patients and healthcare providers with an otherwise unattainable degree of precision. Moreover, once a drug company acquires an enrollee's protected health information pursuant to a valid Health Insurance Portability and Accountability Act (HIPAA) authorization, a drug company faces few limits on downstream uses of those data. This Article illuminates a possible role for patient support program-mediated data collection in two unlawful drug company practices: (1) kickback schemes in coordination with foundations that cover pharmaceutical drug copays, and (2) "product hopping" to a new brand-name drug formulation after patent expiration of an older formulation. The current regime for health data privacy in the United States lacks adequate safeguards to prevent drug companies from exploiting patient support program-derived data to the detriment of patients. The Article ends by proposing practical modifications to the HIPAA Privacy Rule to modernize HIPAA's protections vis-à-vis health data transferred from covered entities to noncovered entities such as drug companies.


Abstract : Many of the recommendations made in the 9/11 Commission's report dealt indirectly with critical infrastructure protection, especially as the goals of critical infrastructure protection have evolved to include countering the type of attack that occurred on September 11. However, relatively few of the recommendations addressed critical infrastructure protection specifically. Those that did called for using a systematic risk management approach for setting priorities and allocating resources for critical infrastructure protection. None of these recommendations advocated a change in the direction of, or the organizational structures that have evolved to implement, existing infrastructure protection policies. Nevertheless, the Commission's recommendations could speed up implementation in some areas, given the attention and renewed urgency expressed by the Commission. Two bills were introduced as legislative vehicles for enacting some or many of the Commission recommendations (S. 2845 and H.R. 10). Like the Commission's recommendations, the language in these two bills, and the subsequent Intelligence Reform and Terrorism Prevention Act of 2004 (P.L. 108-458), for the most part, strengthen or reinforce existing policy and organization associated with critical infrastructure protection. For a more detailed discussion of national policy regarding critical infrastructure protection, including its evolution, implementation, and continuing issues, see CRS Report RL30153, "Critical Infrastructures: Background, Policy, and Implementation." For a discussion on the use of risk management techniques in the context of critical infrastructure protection, see CRS Report RL32561, "Risk Management and Critical Infrastructure Protection: Assessing, Integrating, and Managing Threats, Vulnerabilities, and Consequences." This report will be updated as appropriate.


Naturalistic driving studies (NDS) are revolutionizing road safety research. Naturalistic driving data provide a new window into driver behavior that promises a deeper understanding than was ever possible with crash data, roadside observations, or driving simulator experiments. NDS collect extensive vehicle network data, vehicle internal videos (e.g., drivers and passengers), and vehicle external videos (e.g., forward roadway). The video record of the driver and surrounding road situation often provide a more revealing account of driver behavior. Data size becomes a double edged sword for most NDS. Fully or partially automated procedures are needed for data reduction. Both intentional and unintentional violations of traffic signals can cause severe consequences, like fatal right-angle crashes. Knowing the signal state when the driver navigated through the intersection is the first step towards judging the driver's compliance and analyzing deeper human factors issues. A system that codes traffic signal state from georeferenced front-view videos was developed for use with the Second Strategic Highway Research Program (SHRP2) NDS data. GPS coordinates and a free online map database are used to identify candidate frames from lengthy videos for computer vision processing. The computer vision algorithm uses color histograms and shape matching to detect traffic signals. Vehicle movement is used to select, from multiple signals the one corresponding to the vehicle's traffic lane. Temporal relationship between frames is employed for the purpose of refining detection results. Experiments were conducted on daytime videos and showed reasonable performance given the severe challenges posed by the SHRP2 data. Misclassifications were primarily due to other vehicles' taillights, reddish yellow signals, yellowish red signals, green traffic signs, etc. Misses were due to distant frames with very few pixels corresponding to the signals and reduced color conspicuity compared to background scenes (e.g., green signals and the sky look similar). The system is an insightful first step towards using computer vision techniques to support signal state coding of the large volumes of naturalistic driving video data. Challenges revealed by the experimental results are valuable knowledge for future improvement.


BACKGROUND
Several recent studies have shown that a brief ischaemia applied during the onset of reperfusion (postconditioning) is cardioprotective in different animal models. The potential application of postconditioning to organs different from the heart, i.e. kidney, is not available and is investigated in the present study. We also tested the hypothesis that mitochondria play a central role in renal protection during reperfusion.

METHODS
Wistar rats were subjected to left nephrectomy and 90-min right kidney occlusion. In controls, the blood flow was restored without intervention. In postconditioned rats, complete reperfusion was preceded by 3 min, 6 min and 12 min of reperfusion in a consecutive sequence, each separated by 5 min of reocclusion. Animals were studied for 48 h. Mitochondrial respiratory chain function, rate of hydroperoxide production and carbonyl proteins were measured at the end of postconditioning and 24 h and 48 h after reperfusion.

RESULTS
BUN and creatinine significantly decreased in the postconditioning group as compared to control rats. Mitochondrial respiratory function was significantly impaired in control rats, mainly at the level of Complex II. Postconditioning significantly reduced this mitochondria impairment. The rate of mitochondrial peroxide production was higher in the control group than in the protected group at the end of postconditioning reperfusion. Moreover, mitochondrial protein oxidation was significantly higher in control rats than in the postconditioning group at the end of reperfusion. Conclusions. In the present study, postconditioning reduced renal functional injury and reduces mitochondria respiratory chain impairment, mitochondria peroxide production and protein damage.


Volumetric 3D reconstruction has witnessed a significant progress in performance through the use of deep neural network based methods that address some of the limitations of traditional reconstruction algorithms. However, this increase in performance requires large scale annotations of 2D/3D data. This paper introduces a novel generative model for volumetric 3D reconstruction, Weakly supervised Generative Adversarial Network (WS-GAN) which reduces reliance on expensive 3D supervision. WS-GAN takes an input image, a sparse set of 2D object masks with respective camera parameters, and an unmatched 3D model as inputs during training. WS-GAN uses a learned encoding as input to a conditional 3D-model generator trained alongside a discriminator, which is constrained to the manifold of realistic 3D shapes. We bridge the representation gap between 2D masks and 3D volumes through a perspective raytrace pooling layer, that enables perspective projection and allows backpropagation. We evaluate WS-GAN on ShapeNet, ObjectNet and Stanford Online Product dataset for reconstruction with single-view and multi-view cases in both synthetic and real images. We compare our method to voxel carving and prior work with full 3D supervision. Additionally, we also demonstrate that the learned feature representation is semantically meaningful through interpolation and manipulation in input space.


Recent evidence has demonstrated that young adults achieve improved spoken word recognition performance when words are produced by familiar, as compared to unfamiliar, voices [Nygaard et al., Psych. Sci. 5, 42–45 (1994)]. This benefit for familiar voices is hypothesized to be a result of reduced perceptual normalization demands when listeners have previous knowledge of source characteristics. The present study investigated whether normal‐hearing older listeners exhibit a similar improvement for familiar voices. Younger and older volunteers were trained to discriminate four voices and were then tested on a perceptual identification task with familiar and unfamiliar voices. Although voice discrimination did not differ as a function of age, only the older participants exhibited improved word recognition performance for familiar talkers. Word recognition performance was also examined separately for words at two levels of lexical difficulty: (1) words that are phonetically distinct from others (easy words), and (2) words that are phonetically similar to others (hard words). The largest benefit of voice familiarity was observed for older listeners identifying lexically hard words. The implications of these findings for age differences in the use of voice information will be discussed.


Even though convolutional neural networks (CNNs) are driving progress in medical image segmentation, standard models still have some drawbacks. First, the use of multi-scale approaches, i.e., encoder-decoder architectures, leads to a redundant use of information, where similar low-level features are extracted multiple times at multiple scales. Second, long-range feature dependencies are not efficiently modeled, resulting in non-optimal discriminative feature representations associated with each semantic class. In this paper we attempt to overcome these limitations with the proposed architecture, by capturing richer contextual dependencies based on the use of guided self-attention mechanisms. This approach is able to integrate local features with their corresponding global dependencies, as well as highlight interdependent channel maps in an adaptive manner. Further, the additional loss between different modules guides the attention mechanisms to neglect irrelevant information and focus on more discriminant regions of the image by emphasizing relevant feature associations. We evaluate the proposed model in the context of semantic segmentation on three different datasets: abdominal organs, cardiovascular structures and brain tumors. A series of ablation experiments support the importance of these attention modules in the proposed architecture. In addition, compared to other state-of-the-art segmentation networks our model yields better segmentation performance, increasing the accuracy of the predictions while reducing the standard deviation. This demonstrates the efficiency of our approach to generate precise and reliable automatic segmentations of medical images. Our code is made publicly available at: https://github.com/sinAshish/Multi-Scale-Attention.


Noble metal nanoparticles exhibit a unique optical property known as localized surface plasmon resonance (LSPR), which occurs when interacting light couples to the collective oscillations of the surface electrons. This work investigates the use of various nanoparticles for biosensing based on LSPR.

Triangular silver nanoplates (TSNPs), synthesized using two different methods, and their derivatives, gold-coated TSNPs (AuTSNPs), were investigated for use in refractive index sensitivity-based solution assays. Refractive index sensitivities of these nanoplates were determined and benchmarked against the theoretical calculation predicted by Miller et al.. The first generation TSNPs and AuTSNPs were used for the detection of human C-reactive protein (CRP) and cardiac troponin I (cTnI) and the second generation AuTSNPs were used for the detection of human CRP. In order to address the complex assay design, a simpler aggregation-based assay for the detection of human IgG was implemented using spherical gold nanoparticles. Furthermore, a preliminary study on incorporating the AuTSNPs into a surface plasmon resonance (SPR) sensor was carried out to explore the enhancement effect of the nanoplates on SPR detection.

Nobel metal nanoparticles are found to enhance fluorescence-based biosensing due to a phenomenon known as metal-enhanced fluorescence (MEF) when the nanoparticles are in the vicinity of fluorophores. In this work, the enhancement effects of the AuTSNPs and spherical silver nanoparticles (AgNPs) on the fluorescence were evaluated. A significant enhancement was observed for AgNPs whereas no enhancement was observed for AuTSNPs. Further MEF studies were conducted using various dyes and gold-coated AgNPs. AgNPs were used for enhancing the fluorescence-based assays for human IgG and CRP detection. The limits of detection (LODs) of the IgG and CRP assays were improved by ~ 9-fold and ~ 19-fold, respectively.

This work establishes the potential of plasmonic nanoparticles for highly sensitive biosensing and holds much promise for the improvement of biomedical diagnostics.


\emphCoresets are compact representations of data sets such that models trained on a coreset are provably competitive with models trained on the full data set. As such, they have been successfully used to scale up clustering models to massive data sets. While existing approaches generally only allow for multiplicative approximation errors, we propose a novel notion of lightweight coresets that allows for both multiplicative and additive errors. We provide a single algorithm to construct lightweight coresets for k -means clustering as well as soft and hard Bregman clustering. The algorithm is substantially faster than existing constructions, embarrassingly parallel, and the resulting coresets are smaller. We further show that the proposed approach naturally generalizes to statistical k -means clustering and that, compared to existing results, it can be used to compute smaller summaries for empirical risk minimization. In extensive experiments, we demonstrate that the proposed algorithm outperforms existing data summarization strategies in practice.


In recent decades, different concepts in quality management in textile industries have been introduced. Quality is a highly significant concept and also is the most basic challenge for textile industries. What we called controlling in the past, now has been replaced by "quality control". Among these strategies, production and noble thought in order to recognize and remove not valuable resources on one hand, and six sigma in order to recognize and remove error elements in the process on the other hand, have developed the textile factories. Six sigma and noble methodology are two very strong strategies in for textile companies to reach success and have high quality products. Noble methodology causes a cut in the expenses through optimizing the process whereas six sigma is related to the customers' expectations or needs. It also improves quality through measuring and controlling the deficits. This study is an attempt to improve textile products through two views: six sigma and noble methodology. Each of them this objective by its own .


Introduction Coeliac disease (CD) is present in 1% of the UK population however there are still many undiagnosed cases in the community. The main treatment for this condition is gluten free diet. The role of dieticians in the follow up care of CD patients is crucial especially with regards to educating CD patients about their dietary requirement as well as their role in disease monitoring. The aim of the study is to assess the association of dieticians follow up on the quality of life in CD patients. Methods CD patients who were identified on histology over a 10 years period in East Sussex were sent a socio-demographic questionnaire and the Coeliac Disease Quality of Life (CD-QOL) survey by post. The participants of the study who attend dietician follow up were then compared with those who did not. Multiple linear and logistic regression analyses were used to identify any significant relationships Results Overall, 58 participants (34%) completed and returned the questionnaires. Dietician involvement appeared to be the most important predictor (beta = –0.424, p = 0.001) for overall CDQOL score but surprisingly, the negative value indicates that dietician involvement was associated with a lower quality of life score. Increasing age seemed to have a positive impact (beta = 0.312, p = 0.011) on overall quality of life. However, a change of the recent gluten free prescription (beta = –0.246, p = 0.037) which limits the products available and having initially presented with gastrointestinal symptoms (beta = –0.24, p = 0.044) were found to have negative contributions to the overall CDQOL score. The overall model fit was moderate (R2 = 0.336). Logistic regression was used to identify the likelihood of dietician follow up and the only significant predictor identified was the overall CDQOL score (OR 0.95, p = 0.019) which indicates that those with higher quality of life score were less likely to have dietician follow up. Conclusion Dietician follow up is associated with poorer quality of life but due to the nature of this study, cause and effect cannot be established. It may be that patients who have poorer quality of life chose to see a dietician and longitudinal study is required to further assess this association. This study also suggests that the recent change to the gluten free prescription has negatively impacted the quality of life of those with CD. This fact should be taken into consideration for any future health providers dealing with local CD service provisions. Disclosure of Interest None Declared.


Cladosporium is mainly known as a ubiquitous environmental saprobic fungus or plant endophyte, and to date, just a few species have been documented as etiologic agents in vertebrate hosts, including humans. In the present study, 10 new species of the genus were isolated from human and animal clinical specimens from the USA. They are proposed and characterized on the basis of their morphology and a molecular phylogenetic analysis using DNA sequences from three loci (the ITS region of the rDNA, and partial fragments of the translation elongation factor 1-alpha and actin genes). Six of those species belong to the C. cladosporioides species complex, i.e., C. alboflavescens, C. angulosum, C. anthropophilum, C. crousii, C. flavovirens and C. xantochromaticum, three new species belong to the C. herbarum species complex, i.e., C. floccosum, C. subcinereum and C. tuberosum; and one to the C. sphaerospermum species complex, namely, C. succulentum. Differential morphological features of the new taxa are provided together with molecular barcodes to distinguish them from the currently accepted species of the genus.


The aim of this paper is first to present the results of how first year students of architecture are exposed through an introductory course, (2nd semester, University of Cyprus), to ways of visualizing relations in time rather than objects in space. Further on, the paper will link such pedagogical approach to a broader thinking of making explicit relations, therefore performances in architecture and especially in "architecture as practice". Usually students, through architectural education, become acquainted with means of representation of objects in space. This approach quite often, leads to "architecture as building" approach (object-based design) rather than "architecture as practice" one, (process-based design). The difference between the two is that the latter takes into account not only the object to design but also the systems of actors who are involved in the design process and their priorities. In order that architects find a decisive role within "architecture as practice" approach, they need to be able to visualize relations between project actors, their complex environments, their priorities and the design outcome. Such approach gives to the notion of performance a prominent role and of that of diagram an important tool in communicating such information, especially on how performative are relations between project actors in a process based design approach. To accomplish such objective the workshop uses the 'cosmos' of musical instruments. Every year the workshop focuses on different types of musical instruments in different kinds of context: wind instruments during the rehearsal of Cyprus State Orchestra, chord instruments in "Buena Vista Social Club" movie of Wim Wenders, percussions in "You Tube' video music clips.


Following myocardial infarction (MI), cardiac fibroblasts (CF) proliferate, undergo myofibroblast transformation and generate excess extracellular matrix (ECM). Increased ECM production leads to fibrosis resulting in diastolic dysfunction, ultimately reducing cardiac output. Sphingosine-1-phosphate (S1P), a bioactive lysophospholipid, regulates function of numerous cell types, including certain cardiac cells. The research presented in this dissertation determined the role of S1P in promoting pro-fibrotic actions of CF. Real-time PCR of adult mouse ventricular CF and cardiac myocytes (CM) revealed that, by comparison to CM, CF exhibit higher expression of S1P receptors and sphingosine kinase-1 (SphK1), the enzyme responsible for S1P production. In agreement with this data, both cardiac tissue and isolated cells reveal large cellular pools of S1P in CF, while low levels of S1P are detected in CM. S1P enhanced CF proliferation in an ERK-dependent manner. S1P increased expression of [alpha]-smooth muscle actin ([alpha]-SMA; a myofibroblast marker) and induced collagen production. Both were Rho kinase and S1P₂ receptor-dependent. siRNA to S1P₁ and S1P₃ enhanced basal [alpha]-SMA and collagen production suggesting (1) that myofibroblast transformation and collagen production are inhibited by signaling through these receptors and (2) S1P stimulates basal collagen production through autocrine and paracrine signaling. The well-known pro-fibrotic mediator, TGF- [beta], upregulated SphK1 expression and activity and this was necessary for TGF-[beta]-stimulated collagen production by CF. The anti-S1P monoclonal antibody (mAb) inhibited TGF-[beta]-stimulated collagen production further suggesting that CF utilize autocrine and paracrine signaling wherein SphK produced S1P intracellularly which was secreted and activated S1P₂ located on the cell surface. The anti-S1P mAb, when administered 48 hr after a permanent coronary artery ligation, abolished perivascular fibrosis at two weeks as compared to saline-treated control animals. These findings demonstrate that the S1P signaling machinery is increased in CF compared to CM and that CF may serve as a source of S1P in the heart. In addition, S1P promotes pro-fibrotic function of isolated CF both on its own and in conjunction with TGF-[beta]. Lastly, the anti-S1P antibody reduces cardiac fibrosis in mice following MI. Thus, the anti-S1P mAb may serve as a novel therapeutic to attenuate CF function and resultant tissue fibrosis following ischemic cardiac injury


Background: Superior oblique weakening is a common method to treat A-pattern strabismus. This study aims to evaluate the surgical results of the bilateral superior oblique posterior tenectomy procedure to treat A-pattern strabismus patients who had bilateral superior oblique overaction without objective ocular intorsion.
Methods: The records of 18 consecutive patients who underwent surgery of superior oblique posterior tenectomy close to its insertion with superior oblique overaction (SOOA)-associated A-pattern strabismus between September 1, 2015 and August 31, 2018 were retrospectively reviewed. Ocular alignment, objective torsion, A-pattern and ocular motility were assessed. Ocular alignment was measured in the primary position, 25° upgaze, and 25° downgaze using the prism bar cover test, and torsion was measured using fundus photographs.
Results: A total of 18 patients (mean age: 15 years; 6 female, 12 male) underwent bilateral superior oblique posterior tenectomy and simultaneous horizontal rectus muscle surgery were included. The mean preoperative A-pattern deviation was 15 PD and the mean postoperative A-pattern deviation was 2.25 PD with a mean reduction of 12.75 PD. The mean preoperative superior oblique overaction was 2.28 and the mean postoperative superior oblique overaction was 0.43 with a mean reduction of 1.85. There was no significant correlation between the ocular torsional, vertical alignment change and the superior oblique posterior tenectomy procedure.
Conclusions: Superior oblique posterior tenectomy surgery selectively improved the A-pattern and superior oblique overaction but not affect the primary position vertical deviation, as well as the ocular torsion. It is an effective procedure to treat the mild to moderate superior oblique overaction associated A pattern strabismus without ocular intorsion.


This paper aims to study the uncertainty of the MDOF structural dynamic response, taking not only the interval characteristics of structural physical parameters and geometric dimension, but also the interval characteristics of applied load simultaneously . By means of the description of the interval parameters of uncertain structure with affine forms, the interval structural dynamic equation is studied, and an improved affine arithmetic based on interval division is presented, where correlations between the interval elements in eigenvalue and responses equations are considered, independent uncertain parameters are transformed to affine forms, and the solution of eigenvalue and response equations are transformed into the corresponding certain ones. With general affine arithmetic, the eigenvalue of each order and response bounds are determined by searching for the maximum and minimum in the solutions. Finally, some mathematical examples and a further engineering application confirm the feasibility and validity of this approach.


Terrestrial light detection and ranging technology provides an accurate measurement of individual tree parameters that are essential for managing forest resources, modeling forest fires, planning forest operations, etc. This study aimed to measure individual tree parameters to model a single tree using terrestrial laser scanner (TLS) data. A high-resolution digital terrain model (DTM) was generated using point cloud data (2,800,430 points) to obtain the tree parameters. Next, the diameter of breast heights (DBH), tree heights, tree lengths, tree projection areas, and crown parameters were calculated using 3D Forest 0.42 software. In order to evaluate the capabilities of TLS data, estimated tree parameters were compared with the parameters obtained by field measurements. Regression analysis and paired sample t-test were performed to compare the DBH and tree height values estimated by TLS with those obtained from field measurements. We found a strong relationship between the field measurements and TLS estimates for DBHs (R2 = 0.99) with 1.65 cm root mean square error (RMSE) and tree heights (R2 = 0.98) with RMSE = 0.724 m. The paired Wilcoxon signed-rank test for DBH groups showed no significant difference (P = 0.7285 > 0.05), whereas according to the results of the paired sample t-test for the height groups, there were significant differences between tree heights (P = 0.015 < 0.05; t = -2.55). The results also indicate that TLS is an effective measurement tool to provide highly accurate and precise results for 3D modelling of tree structure parameters without cutting trees. TLS also has great potential to provide many individual tree attributes with high accuracy, which can be used for further evaluations in many forestry disciplines such as silviculture, nature conservation, forest management, and urban forestry.


The analysis of the ΔLOD is of profound significance on climate forecasting, disaster prevention, deep space exploration, geodesy and other fields. With extremely high precision and angular resolution, VLBI plays the irreplaceable role on the analysis of the changes of the length of day. Based on this, in this paper, the ΔLOD sequence and its precision are estimated from VLBI observations during 2008–2010 with comparison with the results published by IVS. The half monthly, monthly, half yearly and yearly periods of the changes of ΔLOD is extracted with spectral analysis. At the same time, the integration curve map of the ΔLOD is made to analyze the seasonal and long-term changes of earth rotation. At last, the causes of the changes of ΔLOD are analyzed


Transcripts containing expanded CNG repeats, which are found in several neuromuscular diseases, are not exported from the nucleus and aggregate as ribonuclear inclusions by an unknown mechanism. Using the MS2–GFP system, which tethers fluorescent proteins to a specific mRNA, we followed the dynamics of single CUG-repeat transcripts and RNA aggregation in living cells. Single transcripts with 145 CUG repeats from the dystrophia myotonica-protein kinase (DMPK) gene had reduced diffusion kinetics compared with transcripts containing only five CUG repeats. Fluorescence recovery after photobleaching (FRAP) experiments showed that CUG-repeat RNAs display a stochastic aggregation behaviour, because individual RNA foci formed at different rates and displayed different recoveries. Spontaneous clustering of CUG-repeat RNAs was also observed, confirming the stochastic aggregation revealed by FRAP. The splicing factor Mbnl1 colocalized with individual CUG-repeat transcripts and its aggregation with RNA foci displayed the same stochastic behaviour as CUG-repeat mRNAs. Moreover, depletion of Mbnl1 by RNAi resulted in decreased aggregation of CUG-repeat transcripts after FRAP, supporting a direct role for Mbnl1 in CUG-rich RNA foci formation. Our data reveal that nuclear CUG-repeat RNA aggregates are labile, constantly forming and disaggregating structures, and that the Mbnl1 splicing factor is directly involved in the aggregation process.


The dissertation critically examines the still evolving process of neoliberal democratization and its impact on the philosophy and structure of the Nigerian media. The return of civil rule in 1999 following decades of military despotism naturally generated a great deal of expectation regarding the prospects of a more democratic media system that would foster popular participation in development and governance. Well over a decade into the democratic experience, not much has changed as the country's media, particularly the broadcasting sector continue to stagnate under military era policies and legislations that automatically became Acts of parliament. The lack of substantive democratization by way of policies and regulations required of a democratic society is further compounded by the selective application of neoliberal policies relative to the political and economic interests of the ruling elite as evidenced by the contrasting policies in broadcasting and telecommunications in which the former remain largely under the stranglehold of the state and the latter almost fully deregulated. Further, the sustained advocacy of coalitions of civil society groups on a host of issues geared towards a more democratic, participatory and accessible media have thus far failed due to the shenanigans of members of parliament and top government officials who want to maintain the status quo. The apparent democratic deficit of the Nigerian media speaks directly to the limits of her current neoliberal democratization. The study draws from both postcolonial and globalization studies as well as critical political economy to explain the complexity of the Nigerian nation and context of its democratization. And given the widespread government abuse of the media in Nigeria, it identifies with the liberal critique of an overreaching state, but not necessarily its unfettered market prescription. Instead, it endorses a social democratic and plural media system not controlled by a leviathan state or behemoth capital; an inclusive system that goes beyond political and economic elites and the urban middle class to also serve the interests of minority groups and cultures, marginal voices and the often overlooked rural peasant populations.


Abstract The National Estuarine Research Reserve System represents a diverse collection of ecosystems among which environmental conditions differ dramatically, making it inherently difficult to determine the extent to which patterns and properties identified in one estuary are transferable to those of any other. The primary objective of our study was to develop a multivariate classification framework for comparison of these estuaries and identify the primary sources of environmental variability in each. Using a 4-year dataset from the National Estuarine Research Reserve System-Wide Monitoring Program, combined with principal components analysis, we identified distinct patterns among 21 reserves that allowed grouping based on the primary factors shaping physicochemical variability. Salinity and temperature were the primary factors shaping variability in the reserves, an observation that was corroborated by similar multivariate analysis of data from 33 published studies of non–National Estuarine Research Reserve systems representing a wide range of coastal and estuarine waters. We then investigated the effect of temperature and salinity on biological processes in these systems by using the ratio of bacterial production to chlorophyll-a as a response variable. Salinity and temperature had different but significant effects on bacterial production/chlorophyll-a ratios, suggesting in turn that these properties contribute to the balance between autotrophic and heterotrophic planktonic processes in estuarine ecosystems. Our study confirms the universal role of salinity and temperature in shaping the variability among even the most diverse systems and provides a valuable classification framework for comparison of reserves within the context of the entire National Estuarine Research Reserve System. Use of this classification approach may provide insight into the extent to which results from investigative studies in one reserve may be applicable to others, a valuable application when the effect of environmental stressors is considered.


Aging frailty is a complex geriatric syndrome that becomes more prevalent with advancing age. It constitutes a major health problem due to frequent adverse outcomes. Frailty is characterized by disruption of physiological homeostasis and progressive decline of health status. Multiple factors contribute to development of frailty with advancing age, including genome instability, DNA damage, epigenetic alternations, stem cell exhaustion, among others. These interrelated factors comprehensively result in loss of tissue homeostasis and diminished reserve capacity in frailty. Therefore, the aged organism gradually represents symptoms of frailty with decline in physiological functions of organs. Notably, the brain, cardiovascular system, skeletal muscle, and endocrine system are intrinsically interrelated to frailty. The patients with frailty may display the diminished reserves capacity of organ systems. Due to the complex pathophysiology, no specific treatments have been approved for prevention of this syndrome. At such, effective strategies for intervening in pathogenic process to improve health status of frail patients are highly needed. Recent progress in cell-based therapy has greatly contributed to the amelioration of degenerative diseases related to age. Mesenchymal stem cells (MSCs) can exert regenerative effects and possess anti-inflammatory properties. Transplantation of MSCs represents as a promising therapeutic strategy to address the pathophysiologic problems of frail syndrome. Currently, MSC therapy have undergone the phase I and II trials in human subjects that have endorsed the safety and efficacy of MSCs for aging frailty. However, despite these positive results, caution is still needed with regard to potential to form tumors, and further large-scale studies are warranted to confirm the therapeutic efficacy of MSC therapy.


In this study, we experimentally analyze the investment behavior of smallholder farmers in Uganda. We ascertain whether, and to what extent, the real options approach and the classical investment theory can predict farmers' investment behaviors. We also examine differences in the investment behavior with respect to the presence of a price floor, which is often used to stimulate investments. Furthermore, we look at learning effects. We consider a problem of optimal stopping, stylizing an option to invest in a project. Our results show that both theories do not explain the observed investment behavior exactly. However, our results suggest that the real options models better predict the decision behavior of farmers than classical investment theory. The presence of a price floor has a significant impact on the investment behavior of Ugandan smallholder farmers. Learning from personal experience during the experiment does not have an effect on the investment behavior. However, we find that specific socio-demographic and socio-economic characteristics affect the investment behavior of farmers.


"Oboy, Oboy," a critical study which dares to grapple with a critically unpopular though not insignificant idea: the determination of ethical rightness in fiction. At a time when literary critics question the validity of ascribing meaning, Truth, or morality to fiction, when philosophers explore the ability or lack of ability of language to convey meaning, and when science suggests that the notions of Truth and reality are at root far more paradoxical and problematic than they once may have seemed, Brian Stonehill's The Self-Conscious Novel: Artifice in Fiction from Joyce to Pynchon takes an admirable risk. In examining the combination of "esthetic neatness and ethical rightness" in modern and contemporary self-reflexive novels, Stonehill sets out to prove that self-consciousness, far from being merely self-indulgent and meaningless, "may in fact be one of the most convincing and compelling forms available to our writers for the expression of what is truly important today" (18).


Onset of the growing season in mid-latitudes is a period of rapid transition, which includes heightened interaction between living organisms and the lower atmosphere. Phenological events (seasonal plant and animal activity driven by environmental factors), such as first leaf appearance or flower bloom in plants, can serve as convenient markers to monitor the progression of this yearly shift, and assess longer-term change resulting from climate variations. We examined spring seasons across North America over the 1900–1997 period using modelled and actual lilac phenological data. Regional differences were detected, as well as an average 5–6 day advance toward earlier springs, over a 35-year period from 1959–1993. Driven by seasonally warmer temperatures, this modification agrees with earlier bird nesting times, and corresponds to a comparable advance of spring plant phenology described in Europe. These results also align with trends towards longer growing seasons, reported by recent carbon dioxide and satellite studies. North American spring warming is strongest regionally in the northwest and northeast portions. Meanwhile, slight autumn cooling is apparent in the central USA. Copyright © 2000 Royal Meteorological Society


This article provides an exploratory analysis of the outputs of state government ethics enforcement. Despite the burgeoning interest in the ethical dimensions of public administration among researchers and practitioners alike, there have been few systematic examinations of the actions and outputs of state ethics commissions and boards. Such data are critical to assessing the cost-effectiveness of the subnational ethics edifice. A review of the characteristics of state ethics commissions reveals substantial variation, suggesting that cost-effectiveness is best analyzed state by state. This research relies on data from the Pennsylvania State Ethics Commission to examine the outputs of ethics enforcement. The examination of formal orders reveals that all types of officials (elected, appointed, and career) run afoul of ethics laws in myriad ways, with varied levels of severity and consequence. This unique analysis of the outputs of state ethics enforcement is an essential component to understanding the nature, and effectiveness, of ethics in practice.


The WTO system has democratic rights spillovers. In this paper, we show how GATT and WTO rules induce memberstates to advance several democratic rights: specifically political participation, due process and access toinformation. We use qualitative and quantitative tools to examine this process. Our quantitative analysis found thatcountries that have been members of the GATT/WTO for longer periods of time saw statistically significantimprovements in our metrics for political participation and due process rights. However, we did not have similarlyrobust findings for access to information. We think this may reflect the limited amount of quantitative data availablefor this period. We note that the WTO is to some degree a bill of rights for foreign market actors. Ironically, inrepressive states, its rules may empower domestic market actors who may not have been able to use existingdomestic remedies to obtain information, influence policies or challenge leadership. We urge other scholars to testour findings about how the WTO and democratic rights became unexpected bedfellows.


Cu2ZnSnS4 (CZTS) thin films were grown on Mo-coated soda lime glass (SLG) substrates by the sulfurization of DC magnetron-sputtered Zn, Sn and Cu metallic precursors under a sulfur atmosphere at 550 °C for 45 min. Understanding the composition and structure of the CZTS absorber layer is necessary to obtain efficient solar cells. With this aim, x-ray diffractometry, Raman spectroscopy, scanning electron microscopy, energy dispersive spectroscopy and x-ray photoelectron spectroscopy were used to investigate the CZTS absorber layers. CZTS absorber films were obtained and found to be Cu-poor and Zn-rich in composition, which are both qualities desired for efficient solar cells. CdS was used as a buffer layer and was grown by the chemical bath deposition technique. The optical properties of CdS films on SLG were searched for using a spectroscopic ellipsometer and the results revealed that the bandgap increases with film thickness increment. CZTS-based solar cells with different CdS buffer layer thicknesses were prepared using a SLG/Mo/CZTS/CdS/ZnO/AZO solar cell configuration. The influence of the CdS buffer layer thickness on the performance of the CZTS solar cells was investigated. Device analysis showed that electrical characteristics of solar cells strongly depend on the buffer layer's thickness. Highly pronounced changes in VOC, fill factor and JSC parameters, which are the main efficiency limiting factors, with changing buffer layer thicknesses were observed. Our experiments confirmed that decreasing the CdS thickness improved the efficiency of CZTS solar cells down to the lowest thickness limit.


We describe a new algorithmic framework for learning multiclass categorization problems. In this framework a multiclass predictor is composed of a pair of embeddings that map both instances and labels into a common space. In this space each instance is assigned the label it is nearest to. We outline and analyze an algorithm, termed Bunching, for learning the pair of embeddings from labeled data. A key construction in the analysis of the algorithm is the notion of probabilistic output codes, a generalization of error correcting output codes (ECOC). Furthermore, the method of multiclass categorization using ECOC is shown to be an instance of Bunching. We demonstrate the advantage of Bunching over ECOC by comparing their performance on numerous categorization problems.


Plant growth promoting rhizobacteria is free living soil microorganisms that directly or indirectly exert beneficial effects on plants. Hundred strains were characterized morphologically and biochemically. Primary screening was carried out for all hundred isolates for IAA, phosphate solubilization, siderophore and nitrogen fixation. Eight isolates F181, F271, F323, F372, F373, F531, ELB1 and ESB4 from different sites and sugarcane cultivars have showed potential for all PGPR activities and were further investigated quantitatively. The isolates could exhibit more than two or three PGP traits, which may promote plant growth directly or indirectly or synergistically. The results shown, F372 achieved the highest phosphate solubilization of 15 mg L-1, and F271 was the most promising IAA producer with 63 mg L-1. Furthermore, most of the PGPR isolates shown antifungal properties like HCN chitinase and protease production. The present study, therefore, suggests that the use of selected PGPR isolates as inoculants might be beneficial for sugarcane cultivation.


For the past few decades it has been known that autistic abnormalities are hereditary. In order to determine what genes are involved in autism, researchers carry out genome screening by means of chromosome maps and markers. Markers that are consistently found in the patient's family members give indication as to which chromosome contains candidate genes that are related to the markers. Candidate genes are studied in two ways, namely on the basis of location and function of the genes. Researchers test the existence of mutation in candidate genes. If mutation is found in the patient's genes, it means that those candidate genes cause abnormalities in the patient. For the past few years researchers have studied 5 chromosomes, namely 2, 3, 7, 15 and X, and candidate genes, namely GABA, UBE3A, GATI, OXTR, FOXP2, WNT2 and RELN. Testing has been made on a great number of genes but no satisfactory result has been achieved and further analysis is still required. However, researchers have recently succeeded in finding out a complete human genome map so that genes that are related to the disease can be more easily identified. Behind the taxing effort and toil in the biomolecular genetic study of autism, there are great hopes that the study will succeed in providing answers to the questions concerning the causes, preventive measures and treatment of autistic abnormalities.


We present a neural network model of how events are stored in and retrieved from episodic long-term memory (LTM). The model is novel in giving an explicit account of the working memory (WM) medium mediating access to episodic memory: it makes a specific proposal about how representations of events and situations in WM interface with representations of events and situations in episodic memory. It also provides the framework for an account of how operations accessing temporally remote situations are reported in language.


Statement of purpose Drug poisoning is a leading cause of death from injuries within the US. Nationally, deaths from opiate use and abuse have quadrupled in the past ten years (CDC). Public health officials and educators are left scrambling to find effective evidence-based strategies for prevention and risk reduction. The goal of this project is to analyse demographic and toxicology data provided by Chester County Coroner's Office to inform opiate abuse and overdose prevention efforts Methods/Approach The Chester County Coroner's Office shared identified demographic data and toxicology reports for 2010–2012 death investigations. Chester County Health Department staff conducted statistical analyses using SPSS v21. Results From 2010 to 2012, the Chester County Coroner's Office investigated 452 deaths. The deceased were primarily white (87.6%) males (63.3%) with a mean age of 45 years. Toxicological panels indicate that 383 of the deceased (84.7%) had opiates in their system. Of those positive panels, 299 had only prescription opiates (no heroin) in the system at the time of death (78.1%), 51 were positive for heroin and some form of prescription opiate (13.3%), and 33 indicated only heroin (8.6%). Of those testing positive for opiates, 110 were positive for recent cannabis use (28.7%) and 68 were positive for ethanol (17.8%). Conclusions The vast majority (91.4%) of opiate-positive panels indicated use of prescribed opiates, while 8.6% were positive for heroin only (n = 33). These findings run contrary to the popular narrative of prescription opiates as the pathway to addiction with heroin often becoming the illicit, lethal end point. Public health education efforts must communicate the lethality of misusing any opiate, especially when combined with alcohol or other drugs. Significance and contribution to the field This investigation demonstrates how data and resource sharing between local government agencies can spur data-driven decision making for public health education while adding value to other public serving departments. Additionally, public health officials can monitor trends in toxicology reports as an evaluation measure for drug abuse prevention and treatment efforts.


The aim of this study was to examine the relationship between antibiotic resistance patterns among Salmonella enterica subsp. enterica Serovar Enteritidis isolates (Salmonella Enteritidis) of human and poultry origin. Antibiotic resistance of 97 Salmonella Enteritidis isolates from 25 chicken meat, 25 chicken intestine and 47 human fecal samples was examined using the National Committee for Clinical Laboratory Standards (NCCLS, 1997) disk diffusion method. Resistance patterns of the isolates were as follows: Of the 25 chicken meat isolates 4 were resistant to some antibiotics. Two isolates (CM15 and CM22) were resistant to ampicillin (AMP), cefuroxime sodium (CXM), ceftriaxone (CRO), trimethoprim-sulphamethazole (SXT) and ampicillin-sulbactam (SAM). Of the other 2 isolates, CM20 showed resistance to ceftriaxone (CRO) and CM23 was resistant to chloromphenicol (C) and cephalexime (CL). Eight human isolates showed 4 different resistance patterns. Five (HF3, HF19, HF20, HF22, and HF25) were resistant to ampicillin (AMP), ampicillin-sulbactam (SAM), tetracycline (TE) and chloromphenicol (C), while resistance to chloromphenicol (C) and cephalexime (CL) was observed in HF32 and HF46. HF13 was resistant to both ampicillin (AMP) and ampicillin-sulbactam (SAM). One of the chicken intestinal isolates was found to be resistant only to cefuroxime sodium (CXM). There was no relationship between antibiotic resistance patterns for Salmonella isolates of different origins. Multiple antibiotic resistance patterns were observed in some isolates. It is important that some isolates of chicken intestine and meat origin showed resistance to antibiotics being used in humans.


Objective To identify and compare tools to assess Evidence-Based Practice (EBP) behaviour among healthcare professionals. Design Systematic review. Data sources MEDLINE, EMBASE, Cochrane Library, PsychInfo and CINAHL up to July 2011. Study selection Titles, abstracts and eligible full text articles were screened by two reviewers independently. Data extraction Relevant data were extracted by one reviewer and checked by a second reviewer. Eligibility criteria for selecting studies: original studies among all healthcare professionals that described the development or use of EBP behaviour assessment tools. Results Of 19 310 identified articles, 172 studies were included. We identified 117 questionnaires, 10 interviews or focus groups, nine observational studies, 27 chart evaluations and nine studies used a combination of methods. Psychometric properties of the questionnaires used were reported in about half of the studies, in seven studies that assess a single EBM step and in six studies that assess a combination of EBM steps. One of these assessed all five steps of EBP. Conclusions Valid and reliable EBP behaviour assessment tools are available. However, only one questionnaire validly assessed all five EBP steps, covering the entire concept of EBP.


Pharyngitis is one of the most common clinical problems. Its causes are multiple, two of the best known being streptococcal infection and infectious mononucleosis. Group A beta-hemolytic streptococcal infections are the focus of diagnostic and therapeutic efforts aimed at reducing the risk of both suppurative and nonsuppurative complications. Several non-group A infections are important to recognize as sources of pharyngitis. In addition, mycoplasmal and chlamydial pharyngitis may be more prevalent than is realized. The possibility of gonococcal pharyngitis should be given special attention because of the severity of complications. Recurrent pharyngitis is difficult to manage. Except for certain specific indications, tonsillectomy remains an unproven therapeutic approach.


We investigate the general features of thermal emission and absorption of radiation in photonic crystals. The light-matter interaction is strongly affected by the presence of the three-dimensional photonic crystal and the alteration of the photonic density of states can be used to suppress or enhance the thermal emissivity and absorptivity of the dielectric structure. Our analysis shows that the thermal response of the system depends on both the elementary absorbers/emitters and the photonic reservoir characteristics. In particular, we demonstrate that, depending on the system configuration, the thermal emission may exceed the free-space radiative energy density given by Planck's law. This modification of the Planck's law is achieved without altering the optical properties of the absorber/emitter medium, which remain consistent with the usual definition of a frequency and angle dependent grey-body. We also evaluate the rate of spontaneous emission, stimulated emission and absorption for thermally driven two-level atomic systems in a photonic crystal, and introduce effective A and B coefficients for the case of a photonic crystal.


Oil sludge is one of the most significant wastes generated in the petroleum industry. A potentially contaminating waste product, with a high content of hydrocarbons and heavy metals. This study is to evaluate the effect of petroleum crude oil contaminated soil and groundwater using MODFLOW Flex software. Existing landfills are non-conforming to the environmental conditions. Despite the fact that there are various techniques used for waste disposal, landfill is the most common mode for the disposal of waste in Iraq. landfill site selection criteria are quite complex process and it depends on several regulation and factors. In this study landfill site selection is performed using Geographic Information System (GIS) for (TOR). Existing landfills in (TOR) are non-conforming to the environmental conditions. In order to determine landfill site, several criteria were examined such as urban centers, land use, airports, pipes, power lines, railways, roads, slope, streams, surface water, industrial areas, oil pipes, liquid gas pipes, soil types are prepared. Each map layer was prepared using GIS and the final suitable map was created by overlay analyses of each criterion map. According to the results, a suitable landfill site was obtained in the study area.


concern to the patient is the greatly reduced discomfort and the much more rapid return to full normal activity that laparoscopic cholecystectomy affords. Careful prospective audit will be required to confirm our early experience that laparoscopic cholecystectomy is as safe as its open counterpart. Mr Reed ends by suggesting that percutaneous cholecystolithotomy and long term drugs or dietary manipulation may prove an alternative treatment for young patients with functioning gall bladders. As one stage percutaneous cholecysto? lithotomy also requires general anaesthesia' we doubt that patients will find this option attractive. I A EYRE-BROOK A P BARLOW


We purified from crude extracts of the hyperthermophilic crenarchaeon Sulfolobus solfataricus a protease that is able to hydrolyse proteins with a pH optimum of 7.5 and a temperature optimum of 70 degrees C. Assays in the presence of classical protease inhibitors showed that the hydrolytic activity is sensitive to thiol-blocking reagents. Fluorescence assays using synthetic peptides demonstrated that the protease has a preference for cleaving glutamic acid residues. The first 12 residues of the protease match the N-terminus residues of a hypothetical protein in the S. solfataricus genome of 95 amino acids in length and calculated molecular mass of 11072 Da. The whole sequence of the protease is not related to any known protein, but it bears a segment which is highly similar to one containing the active cysteine residue in eukaryotic peptidases known as legumains. This is the first protease isolated from S. solfataricus capable of degrading native proteins effectively. Our results add to the knowledge of the intracellular proteolytic machine in hyperthermophilic micro-organisms.