This report discusses the Martin Marietta Intelligent Task Automation Project (ITA). The purpose of the ITA project is to integrate Artificial Intelligence (AI) task planning. path planning. vision, and robotics technologies into a system designed to autonomously perform manufacturing tasks in dynamic or unstructured environments. The application domain chosen for primary demonstrations is dimensional measurement of an F-15 bulkhead. The overall goal is to be able to perform the inspection an order of magnitude faster than the current manual method. which takes about 24 hours for about 1000 inspection points. The project was conducted in two phases. Phase I. completed in December 1984. demonstrated the readiness of the technologies in each of the areas making up the ITA system. Phase II. which was mostly complete in June 1987. demonstrated that the technologies can be integrated into a working system and that the system can be transferred to other applications. The architecture of the ITA system is discussed with an emphasis on the AI components making up the system. The strengths and weaknesses of the architecture and AI techniques applied are discussed.


Bacteria able to generate electricity in microbial fuel cells (MFCs) are of great interest, but there are few strains capable of high power production in these systems. Here we report that the phototrophic purple nonsulfur bacterium Rhodopseudomonas palustris DX-1, isolated from an MFC, produced electricity at higher power densities (2720 +/- 60 mW/m2) than mixed cultures in the same device. While Rhodopseudomonas species are known for their ability to generate hydrogen, they have not previously been shown to generate power in an MFC, and current was generated without the need for light or hydrogen production. Strain DX-1 utilizes a wide variety of substrates (volatile acids, yeast extract, and thiosulfate) for power production in different metabolic modes, making it highly useful for studying power generation in MFCs and generating power from a range of simple and complex sources of organic matter. These results demonstrate that a phototrophic purple nonsulfur bacterium can efficiently generate electricity by direct electron transfer in MFCs, providing another model microorganism for MFC investigations.


Author(s): Miller, James E. | Abstract: The impact of vertebrate animal damage on agricultural production of row crops, forests, horticulture, poultry and livestock production, other wildlife, health of humans and domestic animals, and the protection of human interests is a vital concern of the U.S. Department of Agriculture. The Department recognizes that it is an old and complex problem that does not lend itself to easy answers. Animal damage problems will continue to be a significant concern of USDA and will probably always be controversial, requiring intensive research, educational, regulatory, and assistance programs. The objectives of the Department are to develop and maintain viable programs in animal damage control that are safe, effective and environmentally sound and to cooperate with programs of other departments and agencies, both federal and state, to alleviate the impacts of animal damage on people and their interests.


The Twa of south-west Uganda have reported high morbidity and mortality rates since eviction from their traditional forest lands in 1991. This study seeks to identify their current beliefs with regard to health and hygiene practices. The study is based on semi-structured interviews with 20 individuals in three communities in Kanungu district, Uganda. The Twa attributed most illnesses to changes in their lives, such as food and smells, which fitted a narrative of leaving an idealized forest life. Views with regard to illness prevention ranged from a belief that nothing could be done, to using practices without understanding the reasons for their efficacy (or otherwise), to a use of practices informed by an understanding of Western germ theory. Hygiene behaviours have been adopted where external teachings or practices of neighbours make sense in the Twa world view. It is therefore recommended that future hygiene promotion takes a participatory form, rigorously identifying and working with existing beliefs.


Fish may harbour many pathogens especially parasitic diseases which interfere with the aquaculture production and could constitute a zoonotic importance, especially in developing countries. In this study, 200 freshwater fishes (100 Oreochromis niloticus and 100 Clarias gariepinus) were collected from Abbassa fish farms, Egypt and examined for encysted metacercariae. The prevalence of infection among the two species was 70 and 83 %; respectively and was higher in winter (100 %), than in summer (92 %), spring (60%) and autumn (28 %) for O. niloticus but was same along all seasons (82%) for C. gariepinus. The infection was higher in males (71.4% and 56.6 %) than females (28.6% and 43.4%) for both species; respectively. The common site of infection in O. niloticus were the gills (74.3 %) while in C. gariepinus was the muscles (97.5%). There was a positive correlation between the weight as well as length of O. niloticus and the infection rate but no correlation was detected in C. gariepinus. The recorded encysted metacercariae were identified either by direct microscopic examination (Heterophylids, Clinostomatids, Euclinostomatids, Prohemistomatids, Cyanodiplostomatids and Diplostomatids) or via experimental infection of chicken and resulted two trematodes (Prohemistomum vivax, Mesostephanus applendiculatus). The infected fish showed excessive mucus, loss of scale, some respiratory distress and black to orange spots or nodules on the affected organs. Microscopically, the parasitic cyst was seen embedded in the affected organ. Induced pressure atrophy and degenerative changes and maybe necrosis with or without tissue reactions (mononuclear cells, melanomacrophages and/or connective tissue capsule) depending on the period of infection and the nature of the metabolic products of the parasitic cysts. Based on the high incidence of encysted metacercariae in the investigated fish, we recommend further investigations to identify other trematodes especially those of zoonotic importance, enough inspection and/or cooking of fish to destroy metacercariae, control of snails and migratory birds with increasing fish resistance to the infection.


15N- and 2H-substituted maleimido-TEMPO spin label ([15N,2H]MTSL) and the fluorescent label 1,5-IAEDANS were used to specifically modify sulfhydryl 1 of myosin to study the orientation of myosin cross-bridges in skeletal muscle fibers. The electron paramagnetic resonance (EPR) spectrum from muscle fibers decorated with labeled myosin subfragment 1 ([15N,2H]MTSL-S1) or the fluorescence polarization spectrum from fibers directly labeled with 1,5-IAEDANS was measured from fibers in various physiological conditions. The EPR spectra from fibers with the fiber axis oriented at 90 degrees to the Zeeman field show a clear spectral shift from the rigor spectrum when the myosin cross-bridge binds MgADP. This shift is attributable to a change in the torsion angle of the spin probe from cross-bridge rotation and is observable due mainly to the improved angular resolution of the substituted probe. The EPR data from [15N,2H]MTSL-S1 decorating fibers are combined with the fluorescence polarization data from the 1,5-IAEDANS-labeled fibers to map the global angular transition of the labeled cross-bridges due to nucleotide binding by an analytical method described in the accompanying paper [Burghardt, T. P., & Ajtai, K. (1992) Biochemistry (preceding paper in this issue)]. We find that the spin and fluorescent probes are quantitatively consistent in the finding that the actin-bound cross-bridge rotates through a large angle upon binding MgADP. We also find that, if the shape of the cross-bridge is described as an ellipsoid with two equivalent minor axes, then cross-bridge rotation takes place mainly about an axis parallel to the major axis of the ellipsoid. This type of rotation may imitate the rotation motion of cross-bridges during force generation.


Nihat Polat, Duquesne University Rae Mancilla, Duquesne University Laura Mahalingappa, Duquesne University This study investigates L2 attainment in asynchronous online environments, specifically possible relationships among anonymity, L2 motivation, participation in discussions, quality of L2 production, and success in L2 vocabulary learning. It examines, in asynchronous discussions, (a) if participation and (b) motivation contribute to L2 vocabulary learning, (c) if motivation is related to level of participation in anonymous versus nonanonymous discussions, and (d) if a student's quality of L2 use varies in anonymous vs. nonanonymous discussions. Data from 87 high school students enrolled in a cyber-charter school Spanish II course in the Eastern United States included a preand post-cloze, a vocabulary recognition test, e-documents retrieved from the asynchronous discussions, and demographic information and motivation surveys. Results revealed that students who participated in the asynchronous discussions received significantly higher scores on the post-test than those who did not. In terms of level of participation, nonanonymous forums may have a comparative advantage over anonymous ones for learners with high levels of introjected regulation, whereas for learners with high levels of identified regulation, both forums are advantageous. Introjected regulation was the only significant predictor of success in learning L2 vocabulary. Finally, nonanonymous forums seem to generate higher quality L2 production than anonymous ones.


(abridged) Methods: We derive maps of submillimeter dust optical depth and effective dust temperature from Herschel data that were calibrated against Planck. After calibration, we then fit a modified blackbody to the long-wavelength Herschel data, using the Planck-derived dust opacity spectral index beta, derived on scales of 30' (or ~1 pc). We use this model to make predictions of the submillimeter flux density at 850 micron, and we compare these in turn with APEX-Laboca observations. Results: A comparison of the submillimeter dust optical depth and near-infrared extinction data reveals evidence for an increased submillimeter dust opacity at high column densities, interpreted as an indication of grain growth in the inner parts of the core. Additionally, a comparison of the Herschel dust model and the Laboca data reveals that the frequency dependence of the submillimeter opacity, described by the spectral index beta, does not change. A single beta that is only slightly different from the Planck-derived value is sufficient to describe the data, beta=1.53+/-0.07. We apply a similar analysis to Barnard 68, a core with significantly lower column densities than FeSt 1-457, and we do not find evidence for grain growth but also a single beta. Conclusions: While we find evidence for grain growth from the dust opacity in FeSt 1-457, we find no evidence for significant variations in the dust opacity spectral index beta on scales 0.02<x<1 pc (or 36"<x<30'). The correction to the Planck-derived dust beta that we find in both cases is on the order of the measurement error, not including any systematic errors, and it would thus be reasonable to directly apply the dust beta from the Planck all-sky dust model. As a corollary, reliable effective temperature maps can be derived which would be otherwise affected by beta variations.


Substantial and systematic cross-country variation in entrepreneurship rates has been found in various studies. We attempt to explain such differences focusing on the interaction between institutional factors and population psychological characteristics. Constitutional provisions supporting economic freedom are our measure of the institutional context, whereas we proxy psychological characteristics with a country's endowment of agency culture. We apply an IV-GMM treatment to deal with endogeneity to a data set comprising 86 countries over the period 2004–2013, and we control for de facto variables and other factors that are likely to influence entrepreneurship. Our results demonstrate that agency culture is indeed an important predictor of entrepreneurship and that this effect is moderated by constitutional provisions supporting economic freedom. In particular, the impact of agency culture on entrepreneurship becomes stronger as a country expands the constitutional protection of economic rights.


In this paper, the two-dimensional Fokker-Planck Equation is exactly solved by means of the numerical method. The velocity distribution at the saddle point, the second moments of the coordinate and velocity, and the time development of the nuclear fission rate are studied. The maximum fission rate at a certain viscosity is exhibited by studying the dependence of the fission rate on the nuclear viscosity.


Achieving interoperability, i.e. creating identity federations between different Electronic identities (eID) systems, has gained relevance throughout the past years. A serious problem of identity federations is the missing harmonization between various attribute providers (APs). In closed eID systems, ontologies allow a higher degree of automation in the process of aligning and aggregating attributes from different APs. This approach does not work for identity federations, as each eID system uses its own ontology to represent its attributes. Furthermore, providing attributes to intermediate entities required to align and aggregate attributes potentially violates privacy rules. To tackle these problems, we propose the use of combined ontology-alignment (OA) approaches and locality-sensitive hashing (LSH) functions. We assess existing implementations of these concepts defining and using criteria that are special for identity federations. Obtained results confirm that proper implementations of these concepts exist and that they can be used to achieve interoperability between eID systems on attribute level. A prototype is implemented showing that combining the two assessment winners (AlignAPI for ontology-alignment and Nilsimsa for LSH functions) achieves interoperability between eID systems. In addition, the improvement obtained in the alignment process by combining the two assessment winners does not impact negatively the privacy of the user's data, since no clear-text data is exchanged in the alignment process.


Abstract : Accurate measurements of the size distribution of atmospheric aerosols in the size (radius) range from 0.006 to 2.2 micrometers made along the east coast of the United States--both at a shore site (Wallops Island) and from a ship within 300 km of the coast--are presented. Some measurements at Washington, D.C., are included to contrast urban aerosols with aged continental air off the east coast. As air advects from land to sea, there is a rather rapid decay of particles smaller than 0.05 micrometers during the first day or so. After this initial decay of small particles the size distribution was often found to remain remarkably stable for hours. Significant changes in the size distribution were often associated with changes in air masses and meteorological conditions. Some of the changes can be explained qualitatively. Others, such as a pronounced double peak which occurred occasionally in the fine-particle range, are difficult to understand. Measurements of the activation parameter for submicrometer particles were also made and yield values in the range of 0.1 to 0.55. Using the measured size distribution, electromagnetic extinction was calculated for the wavelength range 0.3 to 12 micrometers. The calculations compare favorably to the measured scattering coefficient at 0.55 micrometers in wavelength. Particles in the radius range 0.1 to 0.3 micrometer made the largest contribution to the total extinction at optical wavelengths on nearly all occasions.


We investigate whether consumer preferences for food products embodying multiple credence attributes are easily satiated. Results from two treatments of an experiment suggest choices are not affected by the order in which attributes are presented. Initial evidence suggests diminishing marginal utility in the number of attributes included in food products embodying multiple credence attributes. However, further testing reveals that preferences are consistent with constant marginal utility in the number of product attributes, suggesting that preferences are not easily satiated.


This work presents a newly developed six-axis magnetic suspension stage for precision motion control. The designed travel volume is 4/spl times/4/spl times/2 mm in translation and 1/spl deg//spl times/1/spl deg//spl times/2/spl deg/ in rotation. A dynamic model of the feedback linearized and uncoupled stage is developed for the purpose of motion control. Model parameter variations are demonstrated through closed-loop system identification. In motion control, a parameter variation model is proposed in conjunction with a reduced order observer to compensate the joined effect of disturbance, modeling error, and cross coupling. Experimental results in terms of positioning stability, motion resolution, rotational motion control, model regulation, large travel multiaxis contouring, and disturbance rejection are shown. Uniform positioning stability and invariant dynamic response within the designed travel volume are illustrated.


A b s t r a c t: This paper reviews the effects of starter cultures with lactic acid bacteria as a factor of increasing quality and in-tensi fi cation of production processes in durable boiled – smoked sausages, type of Burgas. In this regard, the impact of starter cultures in the fi lling, their role in changing the pH value, the content of lactic acid and volatile fatty acids were tested. The two types of starter were used: pure cultures Bi fi dobacterium longum (B 2 ), and mixed cultures Bi fi dobacterium longum (B 2 ) and Lactobacillus plantarum (L 6 ), ratio 2 : 1. To test their impact in stimulating technological process we have produced 10 kg product model of boiled – smoked sausage durable type of Burgas. During the process of draining and drying, an increase in the number of lactobacilli and bi fi d bacteria was recorded. The test results show that the minimum pH value was detected in the period of intensive growth of microorganisms from the starter culture. pH values depend on the composition of starter cultures. Also, rapid decline of pH in the experimental samples with mixed starter cultures was recorded. Considering the amount of lactic acid, intense formation of lactic acid was detected in experimental samples, especially with mixed starter cultures. The results of the examination of the content of volatile fatty acids show that during the process of drying in all of the samples an increase in the value was observed, even a more intensive one in the test samples.


GaN was grown on by MBE using NH3 and a Ga Knudsen cell. The growth kinetics on samples of this polarity were investigated with desorption mass spectroscopy (DMS) and reflection high energy electron diffraction (RHEED). Both techniques were used to observe and control surface termination, Ga condensation and surface temperature. GaN growth and decomposition rates were measured by DMS. Two stable surface terminations were found to exist — N-terminated and Ga-terminated . The N-terminated surface also contained hydrogen which desorbed during growth at a rate proportional to the growth rate. Low temperature reconstructions were only observed by adding weakly adsorbed Ga on top of the Ga-terminated surface. During growth two distinct growth regimes were identified: growth under excess NH3 and growth under excess Ga. Growth is limited in both regimes by GaN decomposition at high temperatures with an activation energy of 3.4 eV. Growth in the excess Ga regime ceased below the Ga condensation temperature. Under conditions of excess NH3, strong but damped oscillations in the specular RHEED intensity were observed on smooth surfaces. Contrary to previous suggestions, the period of these oscillations did not correspond exactly to integral layer deposition and was not characteristic of a narrow growth front. Further, the growth mode changed from island nucleation to step flow with an activation energy of 1.2 eV. Under conditions of excess Ga, the diffraction was 2-D but RHEED intensity oscillations were not observed, indicating a step flow growth mode. In this latter regime RHEED measurements were very sensitive to termination changes on the surface, and the growth rate was found to decrease linearly with increasing Ga flux. This reduction is explained by a model in which weakly adsorbed Ga blocks reaction at strongly bound Ga. A map is presented to provide a framework for categorizing the overall growth.


We investigate the existence of positive solution to nonlinear fractional differential equation three-point singular boundary value problem: , , , , where is a real number, , and is the standard Riemann-Liouville fractional derivative, and (i.e., is singular at ). By using the fixed-point index theory, the existence result of positive solutions is obtained.


The aim of this paper is to validate the modal parameters used in coupled structural finite element and acoustic boundary element algorithm to analysis the structure subjected to diffuse acoustic field. The theoretical deduction of non-symmetric coupled vibro-acoustical modal analysis was introduced firstly. In order to verify the modal truncation frequency how to affect the simulation results, based on the reciprocity theorem used in coupled FE-BE model, three different truncation frequency conditions were performed. The contrastive results show that twice the upper calculation frequency as the truncated modal frequency can make the simulation effectively and efficiently.


Our objective is to determine how chronic illness affects asset accumulation and retirement. Previous studies have found that poor health leads to early retirement, but those studies failed to look at the indirect impact of chronic illness on retirement. Using data from the Health and Retirement Study, we define an illness as chronic if the individual reports having asthma, cancer, heart disease, stroke or diabetes for four or more years. We first estimate how a chronic illness influences asset accumulation. We then estimate how asset accumulation and current poor health influence retirement. We observe that the vast majority of the chronically ill population do not report their general health to be poor nor do they report functional limitations in activities of daily living. Nevertheless, our results indicate that chronic illness leads these people to accumulate fewer assets during their working years and consequently retire later. Neither researchers nor policy-makers discussing the many critical issues surrounding illness and retirement have addressed this issue.


The methods reported for the measurement of distance and medium velocity using ultrasound are based on the principles of pulse radar, pulse Doppler radar, and continuous- wave radar. In this paper, the use of frequency-modulated sonic/ultrasonic radiations for such measurements has been proposed. The required measurement setup has been described, and the mathematical model needed for extraction of distance/medium velocity from the electrical output signal has been developed. The proposed measurement setup has been implemented for distance measurement with commonly used ICs.


We have obtained pulsed lasing operation in 2-5-/spl mu/m diameter microdisk injection lasers using GaInAsP-InP compressively-strained multiple-quantum-well (MQW) wafers around room temperature. The effective cavity volume of the 2-/spl mu/m-diameter device is the smallest among those for any type of electrically-pumped lasers. The threshold current of this device was as low as 0.2 mA. Cavity modes in emission spectra observed under CW conditions coincide well with theoretically predicted whispering gallery modes. Further reduction of diameter to less than 1.5 /spl mu/m will realize the condition for spontaneous emission almost coupling into a single mode, which results in thresholdless lasing operation.


Recent research on network coding (NC) shows that the wireless NC can improve the network throughput in multi-hop wireless ad hoc networks since it can exploit not only the broadcast nature of the wireless channel but also the native physical-layer coding ability by mixing simultaneously arriving radio waves at relay nodes. This paper characterizes the throughput gains of two wireless NC schemes, such as the conventional NC and the analog NC, over the traditional transmission scheduling scheme in wireless ad hoc networks. In particular, we first show the aggregate throughput gains of the conventional NC and analog NC are ( 2n ) / ( 2n - 1 ) and n / ( n - 1 ), respectively, for the n-way relay networks where n ges 2. Second, we formulate a general framework to solve the throughput optimization problem for the transmission scheduling schemes with or without wireless NC. Under this framework, we quantitatively analyze the aggregate throughput gain of wireless NC for different wireless ad hoc network topologies.


This article was migrated. The article was marked as recommended. Laboratory-based intercalated research projects are a popular undertaking for medical students in the UK. Such projects can provide students with a wealth of valuable experiences and the chance to develop new skills that will be highly beneficial to their future careers. Laboratory-based intercalated research projects however represent a very different challenge to other aspects of medical education, with distinct expectations and requirements of students in order for success to be achieved. In this article, the author compiled twelve tips based on current literature and their experiences carrying out a laboratory-based intercalated research project as a UK medical student. These tips will help ensure UK medical students are well prepared before commencing their intercalated research project, in order to maximise the benefits of the opportunities presented to them. Although focused on a UK perspective, many of the tips will similarly be applicable to medical students in other countries conducting laboratory-based projects, albeit in slightly different contexts.


Abstract Extrapolating biosphere-atmosphere CO2 flux observations to larger scales in space, part of the so-called "upscaling" problem, is a central challenge for surface-atmosphere exchange research. Upscaling CO2 flux in tundra is complicated by the pronounced spatial variability of vegetation cover. We demonstrate that a simple model based on chamber observations with a pan-Arctic parameterization accurately describes up to 75% of the observed temporal variability of eddy covariance—measured net ecosystem exchange (NEE) during the growing season in an Abisko, Sweden, subarctic tundra ecosystem, and differed from NEE observations by less than 4% for the month of June. These results contrast with previous studies that found a 60% discrepancy between upscaled chamber and eddy covariance NEE sums. Sampling an aircraft-measured normalized difference vegetation index (NDVI) map for leaf area index (L) estimates using a dynamic flux footprint model explained less of the variability of NEE across the late June to mid-September period, but resulted in a lower root mean squared error and better replicated large flux events. Findings suggest that ecosystem structure via L is a critical input for modeling CO2 flux in tundra during the growing season. Future research should focus on quantifying microclimate, namely photosynthetically active radiation and air temperature, as well as ecosystem structure via L, to accurately model growing season tundra CO2 flux at chamber and plot scales.


ABSTRACT Ancient lakes are centres of adaptive radiation and speciation. The Cladophoraceae endemic to ancient Lake Baikal is a morphologically diverse group nested within Rhizoclonium that may represent a case of sympatric speciation. Recent research using ribosomal DNA markers indicates that these taxa form a monophyletic group but was not able to resolve boundaries between all of the investigated morphospecies due to very low genetic diversity. For this reason, a population genetics approach using more variable markers was investigated. In this study, we developed a set of microsatellites (SSRs) using high-throughput sequencing (HTS) data obtained from three morphospecies of Cladophoraceae from Lake Baikal. To increase amplification rate of the microsatellites across taxa, we performed an in silico cross-validation step comparing the microsatellites retrieved from three HTS datasets and tested the most promising loci on 14 of the mostly endemic morphospecies. We obtained 11 SSRs that cross-amplified among morphospecies, eight SSRs in 12 taxa and three in only four taxa. Our results showed that most loci had more than two alleles, but also displayed variation between and within morphospecies. These results indicate that this group may have gone through polyploidisation. Polyploid systems require a different approach from standard population genetic analyses. We produced 'allelic phenotypes' (presence/absence matrices) to analyse genetic diversity. We showed that similarity indices mostly grouped morphospecies, suggesting that this scoring method will be useful in species delimitation, but further work is needed to elucidate the speciation process in this algal species flock in Lake Baikal.


Object-oriented frameworks are widely used to develop new applications. They provide reusable concepts that are instantiated in application code through potentially complex implementation steps such as subclassing, implementing interfaces, and calling framework operations. Unfortunately, many modern frameworks are difficult to use because of their large and complex APIs and frequently incomplete user documentation. To cope with these problems, developers often use existing framework applications as a guide. However, locating concept implementations in those sample applications is typically challenging due to code tangling and scattering. To address this challenge, we introduce the notion of concept-implementation templates, which summarize the necessary concept-implementation steps and identify them in the sample application code, and a technique, named FUDA, to automatically extract such templates from dynamic traces of sample applications. This paper further presents the results of two experiments conducted to evaluate the quality and usefulness of FUDA templates. The experimental evaluation of FUDA with 14 concepts in five widely used frameworks suggests that the technique is effective in producing templates with relatively few false positives and false negatives for realistic concepts by using two sample applications. Moreover, we observed in a user study with 28 programmers that the use of templates reduced the concept-implementation time compared to when documentation was used.


This paper deals with the problem of computing an approximation system for a given system with time-varying delay such that the energy-to-peak gain of the error system is less than a prescribed scalar. First, a delay-dependent boundedness condition of energy-to-peak gain is given in terms of linear matrix inequalities (LMIs), which recovers the delay-independent case. Then, based on the established delay-dependent boundedness condition of energy-to-peak gain, a sufficient condition to characterize the approximation system is obtained to solve the energy-to-peak model approximation problem in the form of LMIs with inverse constraints. A number of delay-independent energy-to-peak model approximation cases are special cases of a delay-dependent approximation. An efficient algorithm is derived to obtain the approximation models. Finally, examples are employed to demonstrate the effectiveness of the model approximation algorithm.


PURPOSE
The purpose of this systematic review and meta-analysis was to evaluate the potential associations between anthropometric characteristics and bladder cancer risk, synthesizing longitudinal cohort studies.

METHODS
Literature search across MEDLINE, EMBASE, Scopus, Google Scholar and Cochrane Central was performed up to December 31, 2019 and data abstraction was performed independently by two authors. Random-effects (DerSimonian-Laird) models were used to estimate pooled relative risks (RR) and 95% confidence intervals (95%CI); subgroup analyses were performed in geographical region, mean age, publication year, length of follow-up, sample size, method of body mass index (BMI) estimation and adjustment for smoking.

RESULTS
27 studies were included (88 593 bladder cancer cases in a total cohort of 49 647 098 subjects). Increased bladder cancer risk was noted in overweight men (pooled RR=1.12, 95%CI: 1.04-1.21) but not in overweight women. Both obese men (pooled RR=1.14, 95%CI: 1.06-1.22) and women (pooled RR=1.19, 95%CI: 1.02-1.38) showed increased risk. Interestingly, height increase per 5 cm did not seem to affect risk of bladder cancer in men (pooled RR=1.03, 95%CI: 0.99- 1.06) and women (pooled RR=1.02, 95%CI: 0.97-1.06). Larger waist circumference was associated with bladder cancer risk in men (pooled RR=1.18, 95%CI: 1.09-1.26) but not women.

CONCLUSION
Bladder cancer risk seems to be related with obesity overall and central obesity in men. In contrast to other cancer types, height does not seem to affect risk, but more studies are needed to extract safe conclusions.


Bone and soft tissue tumors (BSTT) are relatively poorly understood, hampering the development of effective therapies. Here we report a role for the ubiquitin-specific protease 6 (USP6)/TRE17 oncogene, which is overexpressed upon chromosome translocation in various human tumors, including aneurysmal bone cyst (ABC), and the related benign lesion nodular fasciitis. Ectopic expression of USP6 is known to drive formation of tumors, which recapitulate key features of ABC and nodular fasciitis; however, the identity of USP6's relevant substrates has been obscure. Here we report that the Jak1-STAT3 signaling pathway serves as an essential effector of USP6 in BSTT formation. We found that USP6 directly deubiquitinated Jak1, leading to its stabilization and activation of STAT3. The tumorigenic potential of USP6 was attenuated significantly by CRISPR-mediated deletion of Jak1 or STAT3, or by administration of a Jak family inhibitor. Analysis of primary clinical samples of nodular fasciitis confirmed the activation of a Jak1-STAT3 gene signature in vivo Together, our studies highlight Jak1 as the first identified substrate for USP6, and they offer a mechanistic rationale for the clinical investigation of Jak and STAT3 inhibitors as therapeutics for the treatment of bone and soft tissue tumors along with other neoplasms driven by USP6 overexpression. Cancer Res; 76(18); 5337-47. ©2016 AACR.


An experiment with a strain of Musca domestica susceptible to insecticides and treated with different doses of 2 insects' development inhibitors: Juvenon and S-31183, was carried out. These compounds were added to food supplied to third-stage larvae. On calculating dosage-mortality lines, it was found a greater biological activity in S-31183. Those surviving DL90 were selected for fecundity and fertility studies. The following crossings were carried out: treated females x treated males, treated females x untreated males, untreated females x treated males, untreated females x untreated males (control group). In both compounds it was observed a remarkable reduction in the production and eclosion of eggs, on comparing the first three crossings with the control group. As regards fecundity, sex influences were not observed, whereas fertility was more affected by treated females. No differences were found in connection with the survival of all types of crossings. Morphological affectations are reported in pupae and adults.


Following the opening chapter, which surveys existing literature on the issue of the interaction between individual and group reputation, the remaining chapters each address a simple question to better understand how reputation affects outcomes and incentives. Specifically: Even though good and bad luck might affect short term reputations, do agents end up with the reputations that they deserve, that is one that reflects their genuine underlying ability. The central result of Chapter 2 is that, if the agent knows her own ability (though customers can only make inferences by observing history) then eventually the truth will out. How can an agent, who has proven her ability, commit to working hard. Once an agent has established a reputation then it is a tautology to say that she has no reputational concern. However, if effort is efficient she may want to commit to exerting effort and get adequately rewarded. Chapter 3 shows that one way that she may be able to do this is by hiring and working with a junior agent of uncertain ability. Do teams care any more or less about their reputations than individuals. Joint work with Juanjo Ganuza and introduced in Chapter 4 suggests that an important aspect in answering this question would be to determine whether an agent or team's reputational concerns are primarily about a concern to show itself to be excellent and capable in every task, or about a concern to avoid customers thinking that it is inept. How does industry structure affect a firm's ability to commit to producing high quality. The final chapter discusses this question and suggests that a number of different effects are in play so that there is no simple answer.


With the rapid development of economy and society in China, numerous human activities, including water pollution, overfishing, irrigation, etc., have had a tremendous negative impact on aquatic ecosystems. Ecosystem integrity had also been damaged to some extent, and many problems cannot be effectively resolved by using traditional methods .The research of the causes of changing in water biotic integrity had important practical significance for the sustainable development of China's economy and society. Therefore, there has been a lot of attention on controlling and repairing of water pollution , biotic integrity maintaining in the actual production, The use of new methods , a variety of methods for water pollution combined with analysis, health assessment has also gained great progresses in recent years. This paper reviews the research progress in controlling and protecting water environment and maintaining biotic integrity.


We experimentally demonstrate a low-power MEMS tunable photonic ring resonator with 10 selectable channels for wavelength selection in reconfigurable optical networks operating in the C band. The tuning is achieved by changing the geometry of the slot of a silicon slot-waveguide ring resonator, by means of vertical electrostatic parallel-plate actuation. Our device provides static power dissipation below 0.1 μW, a wavelength tuning range of 1 nm, and a narrow bandwidth of 0.1 nm, i.e. 10 nW static power dissipation per selectable channel for TE mode tuning.


INTRODUCTIONThe craniovertebral abnormalities found in patients with Type VI mucopolysaccharidosis (Maroteaux-Lamy syndrome) are described, and the indications for and outcomes of surgery in this group are assessed. METHODSThe clinical histories and radiological findings in all patients with Type VI mucopolysaccharidosis treated at Royal Manchester Children's Hospital during the past 10 years were reviewed. RESULTSThe typical findings in patients with this disease are of canal stenosis at the level of the foramen magnum and upper cervical spine with or without cord compression. The stenosis is secondary to thickening of the posterior longitudinal ligament. Atlantoaxial instability is rare. Of nine patients under regular clinical review, four underwent decompressive surgery for cervical cord compression. Three of the four showed improvement in their neurological symptoms and signs postoperatively. Of the children reviewed, six had radiological evidence of cord compression, although only those with neurological signs or symptoms were treated surgically. DISCUSSIONDespite the often formidable anesthetic challenge, surgery is indicated in those patients who present with progressive neurological deficit due to cervical myelopathy. Surgery can be undertaken safely if the associated medical problems in these children are recognized and managed appropriately.


The liberal international order seems to be resting on very shaky ground. While the election of Donald Trump and the Brexit vote were startling shocks, these developments represented only the most extreme outcomes of anti-globalization and anti-establishment politics that had been growing for some time. As analysts today struggle to understand these complex phenomena, they most often divide their explanations into two opposing camps: identity politics versus economic anxiety.
I argue that we need instead to understand the new political cleavages in terms of the interactions between economic circumstances and culture, rather than thinking of them as competing explanations. I offer a new way of theorizing about where interests come from, one that focuses on the stark geographic cleavages of the new post-industrial economy and how these material circumstances have created polarized everyday lived experiences. Although I focus on the US case in this short memo, this emphasis on the cultural class cleavages created by the twenty-first century economy should also illuminate some of the drivers for Brexit and the rise of populist politics more generally.


We summarize the history of macroeconometric system modelling as having produced four generations of models. Over time the principles underlying the model designs have been extended to incorporate eight major features. Because models often evolve in response to external events we are led to ask what has happened to models used in the policy process since the financial crisis on 2008/9. We find that models have become smaller but that there is still no standard way of capturing the effects of such a crisis.


In this paper, a (2M,4) scheme of the finite-difference time-domain (FDTD) method is proposed, in which the time differential is of the fourth order and the spatial differential using the discrete singular convolution is of order 2M. Compared with the standard FDTD and the scheme of (4, 4), the scheme of (2M, 4) has much higher accuracy. By choosing a suitable M/spl ges/2, the (2M, 4) scheme can arrive at the highest accuracy. In addition, an improved approximation of the symplectic integrator propagator is presented for the time differential. On the one hand, it can directly simulate unlimited conducting structures without the air layer between the perfectly matched layer and inner structure; on the other hand, it needs only a quarter of the memory space required by the Runge-Kutta time scheme and requires one third of the meshes in every direction of the standard FDTD method. By choosing suitable meshes and bandwidth M, our scheme not only retains higher accuracy but also saves memory space and CPU time. Numerical examples are provided to show the high accuracy and effectiveness of the proposed scheme.


: We studied the effects of ML-236B, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, on serum levels of lipoproteins and ubiquinone-10-in seven heterozygous patients with familial hypercholesterolemia. ML-236B was given at doses of 30 to 60 mg per day for 24 weeks. Serum cholesterol decreased from 390 +/- 9 to 303 +/- 8 mg per deciliter (101 +/- 0.2 to 7.88 +/- 0.2 mmol per liter, mean +/- S.E.M.; p less than 0.001) and serum triglyceride decreased from 137 +/- 18 to 87 +/- 9 mg per deciliter (1.55 +/- 0.20 to 0.98 +/- 0.01 mmol per liter; p less than 0.05). Intermediate-density-lipoprotein (DL) cholesterol, IDL triglyceride, low-density-lipoprotein (LDL) cholesterol, and LDL triglyceride decreased significantly (p less than 0.01, P less than 0.001, and P less than 0.001, respectively). However, there were no significant changes in very-low-density-lipoprotein (VLDL) cholesterol and triglyceride or high-density-lipoprotein (HDL) cholesterol. Serum ubiquinone-10 levels did not change, and LDL levels of ubiquinone-10 decreased by 50 per cent, from 0.39 +/- 0.07 to 0.20 +/- 0.01 microgram per milliliter (P less than 0.05). No adverse effects were observed. We conclude that ML-236B is effective in lowering serum cholesterol without lowering serum ubiquinone-10 in heterozygous patients with familial hypercholesterolemia.


With the rapid development of optical communications and the increasing amount of data exchanged, it has become utterly important to provide effective architectures to protect sensitive data. The use of chaotic optoelectronic devices has already demonstrated great potential in terms of additional computational security at the physical layer of the optical network. However, the determination of the security level and the lack of a multi-user framework are two hurdles which have prevented their deployment on a large scale. In this thesis, we propose to address these two issues. First, we investigate the security of a widely used chaotic generator, the external cavity semiconductor laser (ECSL). This is a time-delay system known for providing complex and high-dimensional chaos, but with a low level of security regarding the identification of its most critical parameter, the time delay. We perform a detailed analysis of the influence of the ECSL parameters to devise how higher levels of security can be achieved and provide a physical interpretation of their origin. Second, we devise new architectures to multiplex optical chaotic signals and realize multi-user communications at high bit rates. We propose two different approaches exploiting known chaotic optoelectronic devices. The first one uses mutually coupled ECSL and extends typical chaos-based encryption strategies, such as chaos-shift keying (CSK) and chaos modulation (CMo). The second one uses an electro-optical oscillator (EOO) with multiple delayed feedback loops and aims first at transposing coded-division multiple access (CDMA) and then at developing novel strategies of encryption and decryption, when the time-delays of each feedback loop are time- dependent.


The purposes of this study were to know the implementation of office supplies
management of Rec-Cross (PMI) of Surakarta, the problems, and the solutions to overcome that
problems. Used a qualitative approach, the result of research showed that PMI Surakarta
implemented the functions of office supplies management to managed their supplies. But, in the
practice, got problems with limited human resources and too many functions of warehouse and
office management. The efforts to overcome those problems included : empowering the industry
apprenticeship's students and Household employees, coping with over functions by asking for help
from other staff and by holding training concerning the instrument use and maintenance, coping
with the narrow warehouse and its location in the same room with the office by utilizing the existing
vertical room, coping with supply release that was not consistent with the predetermined method
by guiding activity accurately and rechecking immediately the stock recording and supply, coping
with Staff of Logistic and Inventory division who did not have time to rearrange the warehouse after
supply releasing by empowering the industry apprenticeship's students, coping with virus problem
delayed data finding and making report by calling the officers to scan the virus, and coping with
roof damage by temporarily solution by putting a rainwater container.


This guide will help students find books and articles on their topics, identify useful web resources, and assist with citing sources. Enjoy!


At first sight a marked difference turns out among the Italian governments of early Renaissance: the means of financing their deficit. There are, on the one hand, communal cities and republics, raising money from citizens through the system of forced or voluntary loans; there are, on the other, princes and lords who exploit services of bankers and merchants. These two different systems of borrowing bring about significant financial and political aspects. In this paper I will examine the main features characterizing the two mechanisms of indebtedness and the implications concerning the emergence of a true financial market connected with state bonds.


Limited availability of P in soils to crops may be due to deficiency and/or severe P retention. Earlier studies that drew on large soil profile databases have indicated that it is not (yet) feasible to present meaningful values for "plant-available" soil P, obtained according to comparable analytical methods, that may be linked to soil geographical databases derived from 1:5 million scale FAO Digital Soil Map of the World, such as the 5 x 5 arc-minute version of the ISRIC-WISE database. Therefore, an alternative solution for studying possible crop responses to fertilizer-P applied to soils, at a broad scale, was sought. The approach described in this report considers the inherent capacity of soils to retain phosphorus (P retention), in various forms. Main controlling factors of P retention processes, at the broad scale under consideration, are considered to be pH, soil mineralogy, and clay content. First, derived values for these properties were used to rate the inferred capacity for P retention of the component soil units of each map unit (or grid cell) using four classes (i.e., Low, Moderate, High, and Very High). Subsequently, the overall soil phosphorus retention potential was assessed for each mapping unit, taking into account the P-ratings and relative proportion of each component soil unit. Each P retention class has been assigned to a likely fertilizer P recovery fraction, derived from the literature, thereby permitting spatially more detailed, integrated model-based studies of environmental sustainability and agricultural production at the global and continental level (< 1:5 million). Nonetheless, uncertainties remain high; the present analysis provides an approximation of world soil phosphorus retention potential.


MDL 105,212 has been identified as a potent, nonpeptide NK-1 and NK-2 receptor antagonist that inhibits effects of substance P and neurokinin A in vitro and in vivo (Kudlacz et al., 1996). In the present study, the compound inhibited capsaicin-induced respiratory effects after p.o. administration (5-50 mg/kg) to conscious guinea pigs; nearly complete inhibition of dyspnea and cough was observed 1 hr after 50 mg/kg p.o., and efficacy persisted for approximately 11 hr. MDL 105,212 reduced pulmonary insufflation pressure and microvascular leakage in ovalbumin-sensitized animals in response to antigen-challenge relative to vehicle-treated animals. Attenuation of early-phase allergic responses may result from MDL 105,212 inhibition of antigen-induced histamine release from sensitized guinea pig lung observed in vitro. Airway hyperresponsiveness to methacholine occurred 24 hr after antigen-challenge in ovalbuminsensitized guinea pigs; this effect was inhibited by pretreatment with MDL 105,212 (50 mg/kg p.o.) 1 hr before ovalbumin exposure without affecting increased bronchoalveolar lavage eosinophil numbers. These data suggest that sensory neuropeptides play a role in some aspects of allergic airway responses and that tachykinin receptor antagonists may be useful in treatment of atopic respiratory diseases.


PURPOSE
To examine the relationship of spherical equivalent (SE) with refractive, corneal, and residual astigmatism.

METHODS
Using stratified cluster sampling, 6,311 individuals were invited and 82.2% participated in this study. Examinations including uncorrected and corrected distance visual acuity tests, refraction, slit-lamp examination, and funduscopy were performed for all participants. Refraction and keratometry were used to calculate refractive and corneal astigmatism, respectively, and their difference was regarded as residual astigmatism.

RESULTS
Refractive astigmatism showed a U-shaped relationship with SE; with every diopter (D) increase in astigmatism, the SE increased by 0.230 D in hyperopes and 0.664 D in myopes (P < .001). With every 1.0 D increase in residual astigmatism, the SE showed 0.376 D myopic shift in myopes (P = .004) and 0.077 D hyperopic shift in hyperopes (P = .224). Mean SE was highest among cases of with-the-rule (WTR) astigmatism (P < .001). Cases of high myopia and high hyperopia mostly had WTR and most emmetropes had against-the-rule (ATR) refractive astigmatism. Residual astigmatism was mostly WTR in emmetropic cases; at higher levels of SE error in myopes and hyperopes, WTR residual astigmatism decreased, whereas ATR and oblique residual astigmatism increased.

CONCLUSIONS
Increases in SE are associated with higher levels of refractive and residual astigmatism among myopic and hyperopic cases. Unlike refractive astigmatism, WTR residual astigmatism was mostly seen in near emmetropic individuals.


Biostimulants offer a novel approach for the regulation of crucial physiological processes in plants. Recently, it has been observed that the application of biostimulants on both seeds and plants may ameliorate to some extent the negative effects of abiotic stresses such as drought, heat, salinity, and others. In the climate conditions of Bulgaria, the early developmental stages of warm climate crops, like maize, often occur under suboptimal temperatures. Although the mitigation of abiotic stress is perhaps the most frequently cited benefit of biostimulant formulations, little is known about their influence on chilling-stressed plants. The aim of our study was to evaluate the effects of a biostimulant from the group of protein hydrolysates on both the growth and the photosynthetic performance of chilling-exposed young maize plants grown in controlled environment. Here, we report that application of a protein hydrolysate increased the performance of chilled maize plants, as demonstrated by leaf gas exchange, photosynthetic pigment content, and chlorophyll fluorescence, but did not affect their growth. Nevertheless, based on the better preserved photosynthetic performance of the biostimulant-treated maize plants exposed to chilling, we assume that under subsequent favorable conditions their growth would recover more quickly as compared to the untreated ones.


It is possible to claim that there is an analogy, in terms of management and programming, between the modality of execution in political contents and the formalities of the application of architectural models, or more precisely in the methods of carrying out such proposals.
The choice and the management of planning strategies go along with the choice of political strategies.
The changes occurring in the politics and democracy can be also found in urban planning politics and involve mainly the public space and the design for the related public buildings.
The emptying of social content in most constitutional democracies, together with the spreading of populist "politics" are phenomena that emerge in the architecture of public buildings and in the way in which the architecture relates to the urban form of their surroundings.
Deprived of their contents, (which are related to their functions), public spaces and public building become non-ruled yet "objectified" spaces targeted for a collective use.
The first analysis, which comes out of my background, led me to look at urban planning in Europe, starting from Italy and keeping the focus on the politics of public spaces and on the ways in which their conception, design and relationship to the city, shape the collective social values, attitudes and demands.
These cases provide some opportunities for a reflection about governance and planning, focussing on the relationship between Democracy and Architecture.


A VIEW FROM SINGAPORE The very first images I had of black-and-white sexual attraction were those from 100 Rifles (Tom Gries, 1969) where Jim Brown makes passionate love to Raquel Welch and in the slick Shaft (Gordon Parks, 1971) where the tough private detective Richard Roundtree has a fine wet time in the shower with a prostitute. The theme of interracial or mixed-race sex and marriage has been, since D. W. Griffith's time, problematic for Hollywood, the world's greatest Dream Factory. The most prominent film to treat this theme seriously is arguably Stanley Kramer's Guess Who's Coming to Dinner (1967). The question of interracial relationship is more sublimated in this film, where Katherine confesses to her mother (Katharine Hepburn), she and Sidney Poitier have not had sex because "he wouldn't let me!" Though controversial in the tumultuous Civil Rights era, it now looks tame and timid as a social...


Blockchain have been an interesting research area for a long time and the benefits it provides have been used by a number of various industries. Similarly, the healthcare sector stands to benefit immensely from the blockchain technology due to security, privacy, confidentiality and decentralization. Nevertheless, the Electronic Health Record (EHR) systems face problems regarding data security, integrity and management. In this paper, we discuss how the blockchain technology can be used to transform the EHR systems and could be a solution of these issues. We present a framework that could be used for the implementation of blockchain technology in healthcare sector for EHR. The aim of our proposed framework is firstly to implement blockchain technology for EHR and secondly to provide secure storage of electronic records by defining granular access rules for the users of the proposed framework. Moreover, this framework also discusses the scalability problem faced by the blockchain technology in general via use of off-chain storage of the records. This framework provides the EHR system with the benefits of having a scalable, secure and integral blockchain-based solution.


This paper is an attempt to show that a large part of Western society no longer operates on the rationalist principles that most of us thought it did, but that it instead runs by magic more akin to that in fantasy works. The term 'magic' is not meant metaphorically or in science fiction author Arthur C Clarke's sense that 'Any sufficiently advanced technology is indistinguishable from magic' (Clarke 1962), but is meant literally in the sense that Frazer (1890, republished 2003) used the term. This means that instead of trying to understand the present and near future by looking at the works of science fiction creators who put forth a rationalist and technological view of the world, we would understand the future better by looking to the fantasy of authors such as Jack Vance, Matthew Hughes, Ursula Le Guin, Piers Anthony and Michael Moorcock.
This magic is manifested through magical thinking and irrational behaviour, where the majority of us use literal spells and incantations in our daily interactions with each other in the networked world, and where we worship capricious gods; most importantly, those spells, incantations and worship actually work, and those gods have actually come to exist.
This paper will also show just how the spread of the computer technology propounded by scientists, technologists and SF writers has inevitably led to the creation of this irrational and magical world. This is partly because of limitations built-in to the formal systems on which these systems are based, leading to an extreme example of the law of unintended consequences. Finally, the paper will explain the mechanism by which magic is literally becoming real by reference to Frazer's two laws of magic: the Law of Similarity and the Law of Contagion.


Current quantification methods of Escherichia coli (E. coli) contamination in water samples involve long incubation, laboratory equipment and facilities, or complex processes that require specialized training for accurate operation and interpretation. To address these limitations, we have developed a microfluidic device and portable instrument prototypes capable of performing a rapid and highly sensitive bacteriophage-based assay to detect E. coli cells with detection limit comparable to traditional methods in a fraction of the time. The microfluidic device combines membrane filtration and selective enrichment using T7-NanoLuc-CBM, a genetically engineered bacteriophage, to identify 4.1 E. coli CFU in 100 mL of drinking water within 5.5 hours. The microfluidic device was designed and tested to process up to 100 mL of real-world drinking water samples with turbidities below 10 NTU. Prototypes of custom instrumentation, compatible with our valveless microfluidic device and capable of performing all of the assay's units of operation with minimal user intervention, demonstrated similar assay performance to that obtained on the benchtop assay. This research is the first step towards a faster, portable, and semi-automated, phage-based microfluidic platform for improved in-field water quality monitoring in low-resource settings.


Background Jacques-Cartier Bridge in Montreal, Canada, was one of the sites with the highest number of suicides in North America. Following extensive research and lobbying by an expert group, a suicide prevention barrier was constructed on the bridge. Aims/Objectives/Purpose (1) To analyse factors contributing to the successful implementation of this suicide prevention initiative; (2) To investigate if the barrier led to displacement of suicides to other jumping sites. Methods We used Shiffman and Smith's Political Priority Framework to analyse the characteristics, ideas, actor strength, and political context associated with the initiative. Poisson regression was used to assess changes in annual rates of suicide by jumping from Jacques-Cartier Bridge, other bridges and other sites after installation of the suicide barrier. Results/Outcomes The presence of powerful, credible and committed actors and coherence of ideas used to convey messages about suicide and its prevention, based on scientific evidence, were important for the success of the prevention initiative. Support of the media was also critical. Results show no evidence of displacement to other jumping sites after installation of the barrier. Significance/Contribution to Field The study provides useful information on the successful implementation of a public health initiative at a local level that can inform future policy initiatives, not only for suicide prevention but other health outcomes. The barrier on Jacques-Cartier Bridge was effective in reducing suicides. The design of a barrier is important for its effectiveness and is preferably considered in the construction of new bridges with the potential to become symbolic suicide sites.


We prove positive mass theorem with angular momentum and charges for axially symmetric, simply connected, maximal, complete initial data sets with two ends, one designated asymptotically flat and the other either (Kaluza-Klein) asymptotically flat or asymptotically cylindrical, for 4-dimensional Einstein-Maxwell theory and $5$-dimensional minimal supergravity theory which metrics fail to be $C^1$ and second fundamental forms and electromagnetic fields fail to be $C^0$ across an axially symmetric hypersurface $\Sigma$. Furthermore, we remove the completeness and simple connectivity assumptions in this result and prove it for manifold with boundary such that the mean curvature of the boundary is non-positive.


Background: Pre-antiretroviral therapy (Pre-ART) patient attrition is a growing concern in Ethiopia. Nevertheless, there is little information that assesses the magnitude and its contributing factors. Objective: This study assessed time to attrition and associated factors among adults enrolled in pre-ART care at Tepi General Hospital in South West Ethiopia. Methods: Records of adult pre-ART patients enrolled at Tepi General Hospital from October 2010 to September 2013 were reviewed to identify factors associated with time to attrition. Time to attrition was defined as the period a patient was enrolled in pre-ART care until lost to follow up or death. Kaplan Meir curve was used to estimate survival time, and log-rank test was used to compare the time to event among different groups of patients. Cox proportional hazard model was used to assess factors associated with time to attrition. Results: We followed 652 pre-ART patients for 337.6 person years of observation from enrolment to pre-ART outcomes. Of these, 179 patients were lost to follow up and 37 patients died, contributing to an overall attrition of 33.13%. In the first six months the attrition rate was 89.8%. Not starting cotrimoxazole prophylaxis (AHR=1.51, 95% CI, 1.02-2.25), being co-infected with tuberculosis (TB) (AHR=2.16, 95% CI, 1.35-3.45), living further than 10 km away from the hospital (AHR=1.44, 95% CI, 1.07-2.0), and undisclosed HIV status (AHR=3.04) were found to be associated with time to attrition. Conclusion: Pre-ART patient attrition rate was high among patients not using cotrimoxazole prophylaxis, TB/HIV co-infected, living >10 km from a health care facility and with undisclosed HIV status. Close follow-up of patients during the first six months' period is highly recommended.


The synaptic neuropil of the olfactory (antennal) lobe of the moth Manduca sexta is subdivided into histologically conspicuous structures called glomeruli that are typical of olfactory systems in vertebrates and invertebrates. Each glomerulus consists of the highly branched neuritic arbors of both primary olfactory axons and antennal‐lobe neurons, bounded by a nearly complete envelope of glial cells. We have studied events occurring during the first half of metamorphic adult development. The first signs of organization of the neuropil into glomeruli are changes in glial cells. Prior to the ingrowth of olfactory axons from the antenna, glial cells form a continuous border around the neuropil. When olfactory axons begin to reach the lobe, glial cells embark on a stereotyped series of changes: the border becomes disrupted, glial cells begin to proliferate and extend processes into the outer regions of the neuropil, and some glial cells migrate toward the center of the neuropil. Shortly thereafter, glomeruli emerge from the neuropil, delineated by glial cells. If, however, afferent axons are prevented from ever reaching the antennal lobe, glomeruli never develop and the glial cells remain almost entirely restricted to a thick layer bordering the neuropil. Thus sensory axons have a direct influence not only on neuronal but also on glial differentiation. Our results lead us to suggest that the glial cells may be in a position to act as intermediaries in developmental interactions between sensory axons and antennal‐lobe neurons.


This thesis investigates the design, operation and use of contemporary demountable buildings, and explores how functional performance can be assessed in small-scale examples for public use alongside with their relationship to other design elements. The research focuses on three case studies that do not require a high-technology building environment or complex construction skills. Demountable buildings are defined as those that are transported in a number of parts for assembly on site. Contemporary demountable buildings respond to ecological issues, social impacts, technological innovation and economic demands. They can be used to measure a society's development in environmental sustainability, innovation and economic growth through various forms. Small-scale demountable buildings fulfil many temporary habitation needs in diverse roles, such as non-emergency transitional housing, ephemeral exhibition buildings and seasonal entertainment facilities.

The purpose of examining functional performance is to assess if, and how, the requirements of the design have been achieved. This enables project operators to address functional performance from a public perspective by reflecting on the scope and ambition of their projects. This thesis draws on existing literature to investigate previous and on-going research relating to demountable buildings, including classification, the construction process and project management. It also examines selected existing evaluation methods that cover principles, modelling and computer-based solutions from a wider research area, including Guidelines Developed by City Council and Culture Sectors; Assessment Methods in Humanitarian Response and Methods in Environmental Assessment.

The research was conducted by combining both quantitative and qualitative research methods, including field research, case studies, interviews, questionnaires and group discussions. Fragmented narratives were transformed into structured evidence, identifying models of best performance in demountable buildings and developing a new method – the Evaluation Conceptual Model – for the effective evaluation and evidencing of the value of demountable buildings in the 21st century. Recommendations for adapting a suitable model to evaluate other design elements in demountable buildings and other types of moveable buildings in further research are suggested and the findings have been used to lay the foundations for a practical evaluation tool for the future.


The significance of the defined issue of psychological and pedagogical support of children affected by the russian military aggression in Ukraine (2022-2023) is substantiated in the article based on the analysis of scientific literature and monitoring of media resources. Several types of crimes against Ukrainian children are presented, such as kidnapping, deportation, forced russification, etc. The questionnaire has been developed and the results of the survey of Ukrainian and Polish students (prospective teachers) with pedagogical experience of dealing with temporarily displaced persons due to the war are presented. Typical challenges they face from a psychological and pedagogical perspective have been identified: psycho-emotional worries of students; communication problems in educational activities; homesickness (which can sometimes be accompanied by depression, sleep disorders and high levels of anxiety); adaptation to new surroundings; periodic air raids, military operations (like those in Ukraine); low motivation to study, lack of interest; double workload for students in Poland (studying in Ukrainian schools online and in foreign schools offline), etc. Based on the qualitative and quantitative analysis of the questionnaire findings, recommendations for the professional training of future teachers to deal with children in crisis, in particular children with war trauma, are proposed. The author emphasizes the importance of developing infomedia literacy, critical thinking, future teachers' skills in creating a media lesson, and media hygiene as the use of electronic communication and distance learning is a priority in the post-war period and requires information safety from ideological manipulations. Considerable emphasis is given to the development of teacher resilience as the capacity of the human psyche to recover, increase stress resistance, and prevent burnout when dealing with students who have suffered from russian aggression or are experiencing other crisis conditions


Aby Warburg's Nachlass, the heart of the Warburg Institute Archive, is complemented by other large holdings which are no less remarkable. Quietly accumulating over the decades, still only provisionally cataloged, the vast corpus of letters filed as "General Correspondence" reveals itself to be a spectacularly rich resource for twentieth-century cultural and intellectual history. The secretariat was efficient: most everything was kept, letters received as well as copies of letters sent, meaning that the visitor to Woburn Square can sit in a single archive, read both sides of exchanges, and follow conversations over years—a rare circumstance. The academic staff maintained contact with an impressively large number of internationally active scholars, working in many fields, and the letters are characteristically substantive. In this article, the author indicates how a book she is presently writing, Warburg Circles, 1929- 1964, has been shaped by these archival holdings. She offers a brief history of the consolidated archive now located on the fourth floor of the Warburg Institute, a story that throws light on recent scholarly trends; and she gives examples of the sorts of historical insight that may be gained from this corpus of correspondence.


Background Insertions and deletions (indels) account for more nucleotide differences between two related DNA sequences than substitutions do, and thus it is imperative to develop a stochastic evolutionary model that enables us to reliably calculate the probability of the sequence evolution through indel processes. Recently, such probabilistic models are mostly based on either hidden Markov models (HMMs) or transducer theories, both of which give the indel component of the probability of a given sequence alignment as a product of either probabilities of column-to-column transitions or block-wise contributions along the alignment. However, it is not a priori clear how these models are related with any genuine stochastic evolutionary model, which describes the stochastic evolution of an entire sequence along the time-axis. Moreover, none of these models can fully accommodate biologically realistic features, such as overlapping indels, power-law indel-length distributions, and indel rate variation across regions. Results Here, we theoretically tackle the ab initio calculation of the probability of a given sequence alignment under a genuine evolutionary model, more specifically, a general continuous-time Markov model of the evolution of an entire sequence via insertions and deletions. Our model allows general indel rate parameters including length distributions but does not impose any unrealistic restrictions on indels. Using techniques of the perturbation theory in physics, we expand the probability into a series over different numbers of indels. Our derivation of this perturbation expansion elegantly bridges the gap between Gillespie's (1977) intuitive derivation of his own stochastic simulation method, which is now widely used in evolutionary simulators, and Feller's (1940) mathematically rigorous theorems that underpin Gillespie′s method. We find a sufficient and nearly necessary set of conditions under which the probability can be expressed as the product of an overall factor and the contributions from regions separated by gapless columns of the alignment. The indel models satisfying these conditions include those with some kind of rate variation across regions, as well as space-homogeneous models. We also prove that, though with a caveat, pairwise probabilities calculated by the method of Miklós et al. (2004) are equivalent to those calculated by our ab initio formulation, at least under a space-homogenous model. Conclusions Our ab initio perturbative formulation provides a firm theoretical ground that other indel models can rest on. [This paper and three other papers (Ezawa, Graur and Landan 2015a,b,c) describe a series of our efforts to develop, apply, and extend the ab initio perturbative formulation of a general continuous-time Markov model of indels.]


Digging mammals are often considered ecosystem engineers, as they affect important properties of soils and in turn nutrient exchange, vegetation dynamics and habitat quality. Returning such species, and their functions, to areas from where they have been extirpated could help restore degraded landscapes and is increasingly being trialled as a conservation tool. Studies examining the effects of digging mammals have largely been from arid and semi‐arid environments, with little known about their impacts and importance in mesic systems. To address this knowledge gap, we investigated the ecological role of a recently introduced population of eastern barred bandicoots (Perameles gunnii) on Churchill Island, Victoria, south‐eastern Australia, from which all digging mammals have been lost. We quantified the annual rate of soil turnover by estimating the number of foraging pits bandicoots created in 100‐m² plots over a 24‐h period. Foraging pit counts could not be completed in each season, and the overall turnover estimate assumes that autumn/winter months represent turnover rates for the entire year; however, this is likely to fluctuate between seasons. Ten fresh and ten old pits were compared to paired undug control sites to quantify the effect soil disturbance had on soil hydrophobicity, moisture content and soil strength. Plots contained between zero and 64 new foraging pits each day. We estimated that an individual eastern barred bandicoot digs ~487 (95% CI = 416–526) small foraging pits per night, displacing ~13.15 kg (95% CI = 11.2–14.2 kg) of soil, equating to ~400 kg (95% CI = 341–431 kg) of soil in a winter month. Foraging pits were associated with decreased soil compaction and increased soil moisture along the foraging pit profile. Eastern barred bandicoots likely play an important role in ecosystems through their effects on soil, which adds to an increasing body of knowledge suggesting restoration of ecosystems, via the return of ecosystem engineers and their functions, holds much promise for conserving biodiversity and ecological function.


The relation between rent sharing and wages has generally been evaluated on average wages. This paper uses a unique employer-employee panel database to investigate the extent of rent sharing along the wage distribution in Italy. We apply quantile regression techniques and control for national level bargaining, unobserved worker and firm heterogeneity and endogeneity. Our findings show that the extent of rent-sharing decreases along the wage distribution, suggesting that unskilled workers benefit most from firms' rents. By applying quantile regressions by occupational categories, we show that the decreasing pattern is mainly driven by blue collar workers, while estimates for white collars are higher and basically constant along the wage distribution. We also provide evidence that unions might represent one of the driver of our findings.


ABSTRACT The Mre11-Rad50-Nbs1 (MRN) complex plays a key role in the DNA damage response, presenting challenges for DNA viruses and retroviruses. To inactivate this complex, adenovirus (Ad) makes use of the E1B-55K and E4-open reading frame 6 (ORF6) proteins for ubiquitin (Ub)-mediated, proteasome-dependent degradation of MRN and the E4-ORF3 protein for relocalization and sequestration of MRN within infected-cell nuclei. Here, we report that Mre11 is modified by the Ub-related modifier SUMO-2 and Nbs1 is modified by both SUMO-1 and SUMO-2. We found that Mre11 and Nbs1 are sumoylated during Ad5 infection and that the E4-ORF3 protein is necessary and sufficient to induce SUMO conjugation. Relocalization of Mre11 and Nbs1 into E4-ORF3 nuclear tracks is required for this modification to occur. E4-ORF3-mediated SUMO-1 conjugation to Nbs1 and SUMO-2 conjugation to Mre11 and Nbs1 are transient during wild-type Ad type 5 (Ad5) infection. In contrast, SUMO-1 conjugation to Nbs1 is stable in cells infected with E1B-55K or E4-ORF6 mutant viruses, suggesting that Ad regulates paralog-specific desumoylation of Nbs1. Inhibition of viral DNA replication blocks deconjugation of SUMO-2 from Mre11 and Nbs1, indicating that a late-phase process is involved in Mre11 and Nbs1 desumoylation. Our results provide direct evidence of Mre11 and Nbs1 sumoylation induced by the Ad5 E4-ORF3 protein and an important example showing that modification of a single substrate by both SUMO-1 and SUMO-2 is regulated through distinct mechanisms. Our findings suggest how E4-ORF3-mediated relocalization of the MRN complex influences the cellular DNA damage response.


The aim of the retrograde filling in apical resection operation is to obtain an effective and hermetic apical sealing. According to the development of technology many materials are now used in apical resection operations for retrograde fillings. An in vitro dye leakage study was performed to test the sealing ability of IRM, MTA, amalgam and zinc-phospate cement materials. Forty single rooted extracted human teeth were used in this study. After cleaning and shaping, all the roots were obturated with zinc-phospate cement and gutta-percha. Teeth were randomly divided into four groups. After root-end resections of the teeth in all groups, 3 mm depth of retrorgade class I cavities were performed in 3 groups with micro-handpiece preperations. Retrofillings of each group were performed with IRM, MTA and silver amalgam. Methylene blue was used to determine the apical leakage. After sectioning the roots longitudinally linear dye penetration in denting and cement was measured with a caliper under stereomicroscope and the results were statistically analyzed.


This research and practice looks to (re) conceptualize the relations between the natural and the social, and between the biological and the cultural. Nature, culture, bodies, texts all unravel into a limitless 'force field of differentiation', a complex interaction of phenomena. In consequence, I have chosen to tackle and combine the exploration of nature and technology while mainly focusing on 'insect' like traits and behaviours because it seems to me that there is quite an uncanny fit between the nature of microscopic mechanisms and the growth of our modern society.


Ecological and epidemiological features of Q-fever throughout its study are represented. The fact of transformation of Q-fever natural focuses to antropurgical focuses is proved. It is established that intraherd focuses, determining epidemiological status of Q-fever, have great persistence. Significant economical loss due to recurrence and chronization of the infection are proved, economical loss from one case of the disease is calculated.


: Six young adult women with recurrent rubella arthritis after HPV-77 DE/5 rubella immunization were studied. Lymphocyte responses to rubella and mumps antigens, and phytohemogglutinin and pokeweed mitogens, were measured in these patients and in 20 immunized hospital employees who did not develop arthritis. All 6 arthritic subjects had pre-immunization hemagglutination inhibition titers of less than 1:8 and their lymphocyte responses to rubella antigen were significantly elevated when compared with those members of the control group with a similar pre-immunization titer of less than 1:8. No significant differences between the 2 groups were found in the other lymphocyte responses.


Many activated sludge wastewater treatment control strategies have been proposed in the literature; however, the literature does not provide a clear basis for comparison of these strategies because of the many confounding influences that have an impact on the system. Complicating the evaluation is the lack of standard evaluation criteria. Simulations provide a cost-effective means for the evaluation of control strategies, but each control strategy must be simulated under the same conditions to ensure unbiased comparisons. To this end, a standardised simulation protocol - a 'simulation benchmark' - was developed. The COST simulation benchmark described in this publication is a fully defined simulation protocol and was developed as a tool for evaluating activated sludge wastewater treatment control strategies. In this instance, the COST simulation benchmark is a comprehensive description of a standardised simulation and evaluation procedure including plant layout, simulation models and model parameters, a detailed description of disturbances to be applied during testing and evaluation criteria for testing the relative effectiveness of simulated strategies. The purpose of this publication is to provide a description of the COST simulation benchmark as currently defined and provide specific information about implementing the benchmark into various simulation software packages (Less)


he burden of stroke is unquestionable in a myriad of aspects. Multiple stroke risk factors are known, and some of them are considered strong and primary while others are considered uncertain and secondary. Among the latter, there is hyperlipidemia. As the acute stroke treatment is costly, the saying that prevention is better than treatment bears a special meaning here. In this discussion, as prosecu-tors from our bar we stand to plead, "Cholesterol – guilty for stroke." of level serum


Abstract: The study comprises a national activity survey of the distribution of time spent on various policing tasks among a sample of over 1,600 community constables and general duty officers. The results of the survey show that about one-third of a typical tour of duty of community constables and about two-fifths of the typical duty tour of general duty officers is spent inside the station. When inside the station the major proportion of their time is spent on general administrative duties including paperwork and when outside the station the major proportion of their time is spent on routine patrol. A comparative analysis of activities across all forces shows considerable variation in the amount of time uniform officers spend on various tasks. An important difference among forces whose officers spend a large amount of time outside the station and forces whose officers spend a small amount of time outside the police station is the amount of time spent on general administrative duties including paperwork. The paper concludes that activity analyses can identify problems in the organisation and deployment of patrol officers and notes plans by HMIC and the Home Office to produce a standard activity sampling package and to encourage forces to use it.


Our work is motivated by the desire to support digital library users in ?getting to grips? with electronic resources. More specifically we are motivated by the desire to support users in understanding how to use, and in which situations it is appropriate to use, particular digital library or electronic resources. This work focuses on lawyers as a specific category of user; Callister [5] highlights that lawyers been traditionally regarded as having poor research skills. Electronic research skills are no exception: Howland and Lewis [8] surveyed U.S. law firm librarians to examine the quality and extent of the electronic legal research skills of summer clerks and first-year associates. They found that these graduates were unable to efficiently or effectively research issues that appear routinely in actual legal cases and concluded that they were not efficient or cost-effective users of LexisNexis and Westlaw (the two biggest digital law libraries in terms of case, legislation and journal coverage). This was despite all of the students having received some training on how to use the libraries while in law school. Digital libraries have traditionally been regarded as difficult to use [4] and based on our contextual observations with academic lawyers, digital law libraries such as LexisNexis Professional and Westlaw are no exception. We believe that this difficulty of use contributes to the problems that lawyers face with electronic legal research. Furthermore, we argue that developing better research skills goes hand-inhand with developing an understanding of the electronic environments in which these skills must be practiced. Our current work is focused on gaining a better understanding of legal academics? and professionals? information seeking behaviour when using existing electronic resources. This understanding will then be used to inform the design of user-centred support tools for digital law libraries (and potentially the design of the libraries themselves).


This paper reports on the exploration of potential design opportunities for social media and technology to identify issues and challenges in involving people in generating content within a cultural heritage context. The work is divided into two parts. In the first part, arguments are informed by findings from 22 in-depth semi-structured interviews with representatives of cultural institutions and with people from a general audience who recently participated in a cultural activity. The key findings show that social media could be used more extensively to achieve a deeper understanding of cultural diversity, with opportunities in redefining the expert, extending the experience space, and decentralising collaboration. To further support these findings, a case study was set up evaluating the experience of a mini audio tour with user-generated (i.e., personal stories from a local audience) vs. non user-generated (i.e., professional stories including facts) narratives. These were delivered using text and 3D sound on a mobile device. The narratives were related to a built environment in central London near world-renown museums, cultural buildings, and a royal park. Observations, a standardised spatial presence questionnaire, and a short open interview at the end of the tour were used to gain insights about participants preferences and overall experience. Thematic analysis and triangulation were used as a means for understanding and articulating opportunities for social media to better involve and engage people using user-generated narratives presented through 3D sound.


Understanding the physical state of intermediate-to-silicic arc magmatic systems is necessary for our petrologic models of these systems. Researchers have generated a plethora of data—geophysical, geochronological, petrological, theoretical—over the past few decades. These data have changed how we view arc magmatic systems, leading to a model of crystal mush that is rejuvenated repeatedly over the lifespan of the magmatic system. However, much data are either circumstantial or incomplete. Paterson et al. (2016; October issue) use a combined set of textural, geochemical, and temporal data to demonstrate the changing physical state of the Tuolumne Intrusive Complex in California over its ~10 million year history. They offer evidence for magmatic erosion and recycling, along with the potential for a "surge growth" of the batholith that allows for significant volumes of magma to exist ephemerally under arc volcanoes.

Most intermediate-to-silicic arc magmas (henceforth "arc magma") are stored ≥3 km depth, so direct observation is impossible. Instead this question has been approached in four main ways: (1) geophysical inspections of active arcs; (2) mineral geochronology; (3) field observations of plutons and; (4) thermal and physical modeling of magmatic systems. Each of these four avenues has their own strengths and shortcomings. Many times the interpretation of these data appears to be at odds.

Some overarching observations can be made about what we know of the state of active intermediate-to-silicic arc magmatic systems:

Geophysical observations (such as seismic tomography) have yielded little evidence for large bodies of fully molten magma persistently underneath arc volcanoes. If anything, only small lenses of partial melt are observed at …


The purpose of this study was to evaluate the effectiveness of using an exercise-based app in increasing student motivation, social support, self-efficacy, and enjoyment in a university physical activity class. A convenience sample of 48 college-aged students (28 males, 20 females) from one university located in the Southeastern United States participated in this study. The study occurred during the students' regularly scheduled activity classes. The students met 4 days per week for 5 weeks during the summer semester. A mixed methods research design was employed for this study. Four major variables were measured pre- and postintervention for the intervention group and postintervention only for the comparison group, including exercise motivation, social support, exercise self-efficacy, and enjoyment. Analyses relied primarily on descriptive (frequency, means) statistics, with inferential statistics (t tests for intra- and intergroup comparisons) as supporting data. Alpha level for statistical significance was set at 0.05, and data were analyzed using SPSS 21.0. Qualitative analysis was used for the focus group data. A significant difference was found between self-efficacy and family support between the intervention and comparison group. Additionally, focus group analysis revealed that students enjoyed the exercise mobile app. The results indicate that the integration of technology, such as app-based interventions, may affect students' enjoyment of physical activity courses.


Neuropathic pain of various etiologies is a frequent symptom in HIV-infected patients that is underdiagnosed and inadequately treated. It requires a multidisciplinary pain approach based on psychosocial factors, diet and exercise, etiologic treatment whenever possible, symptomatic medical treatment, and sometimes, interventional techniques. Medical treatment should be individualized and introduced gradually, with a mind to potential drug interactions. Neuropathic pain responds poorly to conventional analgesics, such as nonsteroidal antiinflammatory drugs and opiates; tricyclic antidepressants and anticonvulsants are the drugs of choice. Before establishing an analgesic treatment, possible drug interactions should be ruled out, mainly those occurring with antiretroviral agents.


Introduction: Bronchoscopy is one of the essential methods for diagnosing lung diseases that is associated with many different uncomfortable complications for patients. The aim of this study was to compare fiberoptic bronchoscopy with midazolam-based anesthesia and lidocaine-based anesthesia. Materials and Methods: The present study is a double-blind clinical trial study that was performed on patients who underwent bronchoscopy from 2017to 2018. Midazolam-based anesthesia was compared with lidocaine-based anesthesia, and then the data were analyzed using SPSS software version 21. Results: 140 patients were studied (mean age total 61.4 years) and among them 52.14% were male and 47.86% were female. Half of the Individuals received midazolam and half of them received lidocaine. The use of lidocaine has been much more satisfactory for physicians and patients, in comparison with midazolam. Complications of bronchoscopy (nausea, decreased arterial blood oxygen saturation, sore throat, cough, and need for intubation) and the duration of bronchoscopy were lower in those who received lidocaine than in those who received midazolam. Conclusion: The use of lidocaine in bronchoscopy reduced complications such as nausea, sore throat, cough, intubation, duration of bronchoscopy, and decreased arterial blood oxygen saturation, and was associated with increased patient and physician satisfaction. Lidocaine can be an appropriate alternative medicine for use in bronchoscopy.


: Psychoactive mushrooms ("magic mushrooms") have been consumed in northern Europe since the late seventies. Recently, the use of hallucinogenic fungi has become popular among young people again. In autumn, psychoactive mushrooms can be collected from their natural habitats throughout Europe. Some species are cultivated in the Netherlands and are sold in "smart-shops" or via Internet. In Germany, dried specimens are sold as "Duftkissen" (aroma pads). The article reviews the common psychoactive species and illustrates medical risks.


In most organs, the bulk of cholesterol is unesterified, although nearly all possess a varying capability of esterifying cholesterol through the action of either sterol O-acyltransferase (SOAT) 1 or, in the case of hepatocytes and enterocytes, SOAT2. Esterified cholesterol (EC) carried in plasma lipoproteins is hydrolyzed by lysosomal acid lipase (LAL) when they are cleared from the circulation. Loss-of-function mutations in LIPA, the gene that encodes LAL, result in Wolman disease or cholesteryl ester storage disease (CESD). Hepatomegaly and a massive increase in tissue EC levels are hallmark features of both disorders. While these conditions can be corrected with enzyme replacement therapy, the question arose as to whether pharmacological inhibition of SOAT2 might reduce tissue EC accretion in CESD. When weaned at 21 days, Lal−/− mice, of either gender, had a whole liver cholesterol content that was 12- to 13-fold more than that of matching Lal+/+ littermates (23 versus 1.8 mg, respectively). In Lal−/− males given the selective SOAT2 inhibitor PRD125 1,11-O-o-methylbenzylidene-7-O-p-cyanobenzoyl-1,7,11-trideacetylpyripyropene A in their diet (∼10 mg/day per kg body weight) from 21 to 53 days, whole liver cholesterol content was 48.6 versus 153.7 mg in untreated 53-day-old Lal−/− mice. This difference reflected a 59% reduction in hepatic EC concentration (mg/g), combined with a 28% fall in liver mass. The treated mice also showed a 63% reduction in plasma alanine aminotransferase activity, in parallel with decisive falls in hepatic mRNA expression levels for multiple proteins that reflect macrophage presence and inflammation. These data implicate SOAT2 as a potential target in CESD management.


Summary Fondaparinux is a synthetic pentasaccharide that selectively inhibits factor Xa (FXa) in an antithrombin-dependent fashion.This newly developed anticoagulant is used in the prevention and treatment of venous thromboembolism. Recently, we showed that fondaparinux reduces inflammation and protects the kidney from ischemia-reperfusion (I/R) injury. However, the relative contributions of the anticoagulant and anti-inflammatory activities of fondaparinux to the observed protection is unknown.To address this, we chemically modified fondaparinux to abolish its affinity for antithrombin and analyzed the effect of this non-anti- coagulant (NAC)-pentasaccharide on binding of U937 cells to P-selectin in vitro and on inflammation in a murine model of kidney I/R injury. NAC-pentasaccharide was as effective as fondaparinux at inhibiting the binding of U937 cells to P-selectin.In addition, NAC-pentasaccharide significantly reduced IL-6 and MIP-2 expression and injury in the kidney I/R model.These findings indicate that the anti-inflammatory activity of fondaparinux can be dissociated from its anticoagulant activity and that NACpentasaccharide is protective in kidney I/R injury.