Background: Prostate cancer is the 6th leading cause of cancer death worldwide. Androgen Deprivation Therapy (ADT) in prostate cancer enhances the risk of Rheumatoid Arthritis (RA). Acetylsalicylic Acid (ASA) can be potentially repurposed against prostate cancer and arthritis. However, its efficacy is low and use is associated with nephrotoxicity as well as gastrotoxicity. Curcumin with reported ability to potentiate anti-inflammatory effects and reduce oxidative stress, can be used as a complementary therapy to enhance efficacy of ASA against prostate cancer and arthritis. This can also minimise ASA induced nephrotoxicity and gastrotoxicity. Aim and Objectives: To evaluate the ability of curcumin to enhance efficacy of ASA against prostate cancer, arthritis while minimising its adverse effects. Methods: In-vitro anticancer activity was assessed in DU-145 (Androgen-independent) and LNCaP (Androgen-dependent) cells. Effect against arthritis was evaluated in complete Freund's adjuvant (CFA) induced arthritis model in rats. Biochemical factors, radiology and histopathology were examined. Protection against kidney dysfunction and ulceration was determined. Results: Curcumin on co-administration with ASA (ASA+Cur) (25 μM + 25 μM) showed higher efficacy against DU-145 and LNCaP cell model. This co-use showed significant (p<0.001) inhibition of arthritis index (AI). The erythrocyte sedimentation rate (ESR) and rheumatoid factor (RF) were significantly (p<0.001) decreased from their elevated level. It also reduced tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β) and interleukin 6 (IL-6) at the molecular level. While it showed moderate gastro-protection, there was no adverse effect on kidney functions. Conclusion: Curcumin seems to enhance the effect of ASA against androgen dependent as well as androgen independent prostate cancer while reducing arthritis. Simultaneously, it reduces ASA induced gastrotoxicity and prevents nephrotoxicity.


This paper reports new data on biostratigraphy, stratigraphy and syn-sedimentary deformation of the so-called "Boeotian Flysch" cropping out in key areas in Central Greece (Levadhia, Parnassus, Iti). Because of its age, sedimentary evolution and mechanisms of the syn-sedimentary deformation, the Boeotian Flysch represents a key element providing useful hints on the Cretaceous paleogeography reconstruction of the Dinaric-Hellenic Chain and in particular on the obduction at the Jurassic-Cretaceous transition in the eastern continental margin of the Adria plate. We provide here a new detailed study of different features of the Boeotian Flysch, with particular emphasis on reconstructing and dating its stratigraphy. In particular, we recognized two distinct turbiditic systems: the Lower Boeotian Flysch (Tithonian?-Aptian) and the Upper Boeotian Flysch (Cenomanian-Coniacian), which are separated by a main unconformity marking a sedimentary hiatus lasting from Aptian p.p. to Albian. By means of the improvement of the age, stratigraphy and deformation history of this syn-tectonic turbidite deposit, we therefore contribute to better define the chronology of the early phases of continental stage of obduction, and the following continental collision between Adria and Eurasia. The analyses of the collected data allowed us to propose for the Boeotian Flysch a deposition within an obduction-related foredeep basin associated with a flexural depression/flexural bulge due to crustal loading of westerly-directed ophiolite obduction.


Liposomes possess good biocompatibility and excellent tumor-targeting capacity. However, the rapid premature release of lipophilic drugs from the lipid bilayer of liposomes has negative effect on the tumor-targeted drug delivery of liposomes. In this study, a lipophilic antitumor drug—chlorambucil (CHL)—was encapsulated into the aqueous interior of liposomes with the aid of albumin to obtain the CHL-loaded liposomes/albumin hybrid nanoparticles (CHL-Hybrids). The in vitro accumulative release rate of CHL from CHL-Hybrids was less than 50% within 48 h, while the accumulative CHL release was more than 80% for CHL-loaded liposomes (CHL-Lip). After intravenous injection into rats, the half-life (t1/2β = 5.68 h) and maximum blood concentration (Cmax = 4.58 μg/mL) of CHL-Hybrids were respectively 1.1 times and 3.5 times higher than that of CHL-Lip. In addition, CHL-Hybrids had better tumor-targeting capacity for it significantly increased the drug accumulation in B16F10 tumors, which contributed to the significantly control of tumor growth compared with CHL-Lip. Furthermore, CHL-Hybrid-treated B16F10 melanoma-bearing mice displayed the longest median survival time of 30.0 days among all the treated groups. Our results illustrated that the proposed hybrids drug delivery system would be a promising strategy to maintain the controlled release of lipophilic antitumor drugs from liposomes and simultaneously facilitate the tumor-targeted drug delivery.


We present a novel technology suitable for situated displays, called ThinSight. It combines up close zero-force multi-touch interaction, with inte- raction and data exchange from a distance using a mobile device. The novelty of ThinSight lies both in the combination of these features and in the thin form- factor of the hardware which can be fully integrated into commercially available LCDs without affecting display quality. This readily deployable situated display technology opens up many new ubiquitous computing possibilities.


Abstract The difference between the method of metaphysics and the method of mathematics was an issue of central concern for Kant in both the Pre-Critical and Critical periods. I will argue that when Kant speaks of the 'philosophical method' in the Doctrine of Method in the Critique of Pure Reason (CPR), he frequently has in mind not his own methodology but rather the method of conceptual analysis associated with rationalism. The particular target is Moses Mendelssohn's picture of analysis contained in his submission for the 1763 Prize Essay competition. By the time of the first Critique, I argue, Kant wants to maintain his own longstanding commitment to the distinctness of the methods of metaphysics and mathematics. However, Kant wants to use this same analysis of the source of the distinction to diagnose the origins of the dogmatism that is engendered by the method of the rationalists.


We evaluate linear stochastic discount factor models using an ex-post portfolio metric: the realized out-of-sample Sharpe ratio of mean–variance portfolios backed by alternative linear factor models. Using a sample of monthly US portfolio returns spanning the period 1968–2016, we find evidence that multifactor linear models have better empirical properties than the CAPM, not only when the cross-section of expected returns is evaluated in-sample, but also when they are used to inform one-month ahead portfolio selection. When we compare portfolios associated to multifactor models with mean–variance decisions implied by the single-factor CAPM, we document statistically significant differences in Sharpe ratios of up to 10 percent. Linear multifactor models that provide the best in-sample fit also yield the highest realized Sharpe ratios.


The aim of this study is to identity successful business conducts carried out by the company. The successful business conducts identified are: (1) Employing skillful marketing personnel, (2) Having a wide marketing channels, (3) Application of production contract, (4) Utilizing brokers in marketing the product, (5) Utilizing secondhand containers to reduce cost. The method used from this study is SWOT analysis with primary and secondary data, which are collected through literature and interview. Based on the results of the SWOT analysis, there were some suggestions to PD. Budi Lestari in order to develop its business by : (1) Increasing working capital, (2) Increasing the quality of human resources, (3) Making promotions, (4) Increasing the machine technologies utilizing, (5) Finding new bottles using altenatives in solving problem of getting used bottles, (6) Using labels that includes the special qualities of the drinks to explain the characteristic and quality from each product made, (7) Selecting the distribution of used bottles facilities. Beside that, suggestions given from this study can be an input to the company in raising its sales volume as an effort to fulfill market's demand, includes mini and super markets.


Objectives. To evaluate independent predictors of 30-day mortality in patients with severe sepsis or septic shock. Background. Severe sepsis and septic shock are associated with increased mortality. Admission APACHE II score is the gold standard for assessing prognosis in critically ill, but several other predictors of mortality have been evaluated. Methods. We retrospectively evaluated clinical and laboratory data in adult patients with severe sepsis or septic shock as predictors of 30-day mortality. Results. Thirty-day mortality was 62.7%. Nonsurvivors in comparison to survivors were significantly more likely to be trea-ted with noradrenalin, renal replacement therapy, mechanically ventilated, to have suffered a fungal infection, had lower admission arterial pH, increased admission Acute Physiology, Age, Chronic Health Evaluation (APACHE) II score and a higher peak lactate level (5.6 ± 6.2 vs 3.1 ± 1.75, p=0.021). Binary logistic regression demonstrated that only peak in-hospital serum lactate level was a significant independent predictor of 30-day mortality (OR 1.367, 95% CI 1.041 to 1.795, p=0.025). Conclusion. Only peak in-hospital lactate significantly and independently predicts 30-day mortality in severe sepsis or septic shock medical patients.


Children with cerebral palsy (CP) and quadriplegia or severe diplegia suffer from highly reduced mobility and consequent constipation. Clinicians recommend standing frames to exercise the support reaction in this population, sharing the opinion that the upright position may facilitate intestinal transit, although no evidence supports this assumption. We conducted this study to determine the effects of the standing frame on spontaneous evacuation in children with CP. Moreover, we studied its effects on the frequency of induction of evacuation, the characteristics of the stool and the pain suffered by the child due to constipation and/or evacuation. We implemented a single-subject research design in one chronically constipated child with CP and quadriplegia, Gross Motor Function Classification System Level V. To monitor the effects of the standing frame, we measured the outcome of interest throughout the study using a daily diary and the Bristol Stool Scale. This study was approved by the local Ethics Committee. This study has several limitation; primarily, the use of a single-subject research design only makes possible the visual analysis of data obtained from a unique patient. So, by themselves, data obtained do not allow us any generalization for the target population. Future research should verify our results collecting more data and also investigating the effect of the standing-frame on respiratory functions. Although the standing frame did not affect the frequency of evacuations or the characteristics of the stool, its employment reduced the inductions of evacuation and the related pain suffered by the child. However, this study has several limitations, such as the lack of generalization due to the fact that we studied a unique patient and the overall brevity of the study due to external circumstances. Therefore, we suggest future research to verify our results, also investigating the effect of the standing frame on respiratory functions. Relevance to clinical practice. The standing frame may positively influence the management of constipation of these children, possibly improving their quality of life.


The phenomenon of malaise is on the rise at universities, reflecting a deteriorating psychological state that is a combination of anxiety and stress factors. This psychological and emotional upheaval within students is indicative of a fundamental existential issue. In fact, hidden behind the choice of an educational program is the significance given by the student to their life goals. It is this dimension of attributing meaning to one's education and, more broadly, to one's life (the existential dimension) that we have sought to explore. We hypothesized that a stable investment in one's life goals and a sense of psychological wellbeing during one's studies could be fostered by reflective work done alongside the educational process. Our research took the form of a mixed methodological approach to the attribution of meaning to education, including an interpretive phenomenological analysis (IPA), and the experimentation of support for the meaning of education. Four dimensions of meaning were found to be observable in varying degrees in all students, each playing a specific role. Moreover, this research has confirmed that the meaning of studies is not to be understood solely in terms of education, but is part of a singular life story. Reflective work, developing meaning, facilitated by others (advisor, teacher, etc.) can help preserve/restore the feeling of wellbeing. It should be noted that, as the work presented in this article predates the pandemic, we will not address the amplifying effects of this health crisis on existential issues, which some recent studies are beginning to highlight.


Introduction Trisomy is the cause of Down syndrome (trisomy 21) and is present in one in four spontaneous abortions (SAs), the most frequent (5-10%) being trisomy 16. In the gene dosage hypothesis, the trisomic phenotype is due to overexpression of specific genes on the trisomic chromosome, such that different trisomies will have different patterns of gene expression. In the amplified instability hypothesis, the trisomic phenotype is due to the extra chromosome disrupting cellular homeostasis non-specifically (ie, regardless of chromosome type), which causes an amplified sensitivity to interindividual environmental and genetic variation, such that trisomy will show increased interindividual variability in gene expression. Methods Protein kinases (n = 75), fundamental components of signal transduction, were profiled in placental chorionic villus cultures from first-trimester SAs: trisomy 16 (T16) (n = 3), trisomy 15 (T15) (n = 3), and euploid (Eu) (n = 4). Protein and RNA expression were profiled with a 2D Western blot and 14,000 oligonucleotide array. Immunochemistry showed all cultures consisted of fibroblasts. Maternal decidual contamination was ruled out by microsatellite PCR. Results At the protein level, 7 kinases had significantly different expression (p < .05) in T16 vs Eu (CDK1, CDK7, PKC-", PKG1, ERK1, S6K p70, IKK-α), of which 2 were also different in T15 vs Eu (S6K p70, IKK-α). Seven kinases were only different in T15 vs Eu (CK1-", SRC, CDK9, DNAPK, MEK2, PKC-z, PKC-β). Interestingly, 13 of these total 16 differences involved lower expression in the trisomy (Sign test, p = .021). For the kinases with genes on chromosome 16 or 15, only ERK1 (16p11) was significantly overexpressed (at both the RNA and protein levels) in the trisomic state. In addition, the coefficient of variation (V) was used to quantify interindividual variability in gene expression. At the protein level, V was significantly higher in T16 (V = 0.49) and T15 (V = 0.52) compared to Eu (V = 0.28) (both p < .001); but at the RNA level, V was lower in T16 (V = 0.19) and T15 (V = 0.25) compared to Eu (V = 0.32) (p < .001, p = .02). Conclusions The differential expression pattern between T16 and Eu, distinct from the pattern between T15 and Eu, as well as the dose-related increase in ERK1 expression in T16, supports the gene dosage hypothesis. The high V for both trisomies at the protein level supports the amplified instability hypothesis, although it was not initiated at the RNA level, suggesting a (post)-translational origin. This study provides evidence that the mechanisms of gene dosage and amplified instability can operate simultaneously in human trisomy.


As part of its action plan against base erosion and profit shifting(BEPS), the OECD (2015) has proposed six indicators to measure profit shifting activity. These indicators add to past and ongoing efforts in academic tax research to empirically identify the scale and tax sensitivity of international profit shifting. In this paper, we discuss whether the proposed OECD indicators indeed represent methodological advances and critically assess their informative value. While a certain need for "easy-access" indicators to measure the relevance of the base erosion problem seems justified, our discussion reveals that the indicators come up with certain shortcomings, many of them acknowledged by the OECD (2015) itself, that pre-vent them from reliably tracing profit shifting activity in available international data. With one notable exception, the OECD's indicators lack consistent counterfactuals and comparison groups which are essential benchmarks for the observed data. Even the most promising approaches require representative and timely data that covers firms' global activity, including tax haven operations. With better access to such high-quality micro-level data, it will be more promising to empirically isolate the effects of profit shifting from relocations of real economic activity and value creation.


A prominent international-relations theory posits that mutual optimism, due to two sides holding divergent estimates of their relative bargaining power, causes interstate conflict. We develop a theory of mutual optimism in which conflicting bargaining power estimates arise from asymmetric information about which, if any, third parties will join either side in a military dispute. We contend that secret alliances can generate mutual optimism, which increases the probability of conflict. By exploiting secret alliances as a measurable source of private information, we provide the first systematic test of mutual optimism that directly assesses a state's secret capabilities. Optimism exists when a state's secret allies are more numerous or powerful than anticipated by opponents. Our empirical tests—as well as robustness checks—strongly support our theoretical expectation. We conclude that mutual optimism is an empirically, as well as theoretically, important cause of interstate conflict.


Malignant breast images may include opacities (stellar--rounded with blurred margins), microcalcifications, opacities with microcalcifications, asymmetric fibroglandular tissue, or distortion of the mammographic pattern. Secondary signs may also be present, such as skin thickening, skin or nipple retraction, prominent vascularisation, axillary lymph nodes. The aim of this paper is to describe the different aspects and to make the differential diagnosis from benign tumors and normal tissue.


We identified a total of 690 negotiated trade agreements between 1945 and 2009 of which we have coded 404 agreements for which treaty texts and appendices were available. We aim to have a database for about 550 agreements by 2012. We have coded agreements for a total of 10 broad sectors of cooperation, encompassing market access, services, investments, intellectual property rights, competition, public procurement, standards, trade remedies, non-trade issues, and dispute settlement. For each of these sectors, we have coded a significant number of items, meaning that we have about 100 data points for each agreement. The resulting DESTA database is — to the best of our knowledge — by far the most complete in terms of agreements and sectors covered. This dataset fills a crucial gap in the field by providing a fine-grain measurement of the design of PTAs. Among others, we think that DESTA will be of relevance for the literatures on the signing of PTAs; the legalization of international relations; the rational design of international institutions; the diffusion of policies; the political and economic effects of trade agreements; power relations between states; and forum shopping in international politics. This working paper describes the DESTA data set and provides selected descriptive statistics. The overview puts emphasis on variation in design over time and across regions.


Restorative justice has become a fashionable term both in Canadian and foreign legal and social policy discourse. Restorative justice is certainly not a new idea. In fact, it is foundational to our very ideas about law and conflict resolution. There is, nevertheless, a lack of clarity about the meaning of this term. Often it is used as a catchall phrase to refer to any practice which does not look like the mainstream practice of the administration of justice, particularly in the area of criminal justice. Little attention has been spent attempting to articulate what distinguishes a practice as restorative. Rather, we have been content simply to identify what restorative justice is not - namely two lawyers, a jury and/or judge in a courtroom.


This application note describes the design of a 3-phase brushless DC (BLDC) motor drive based on Freescale's ColdFire MCF523x microprocessor. The application design takes advantage of the enhanced time processing unit (eTPU) module, which is used as a motor control co-processor. The eTPU completely handles the motor control processing, eliminating the microprocessor overhead for other duties. BLDC motors are very popular in a wide array of applications. Compared to a DC motor, the BLDC motor uses an electric commutator, replacing the mechanical commutator; thus making it more reliable than the DC motor. In BLDC motors, rotor magnets generate the rotor's magnetic flux, allowing BLDC motors to achieve higher efficiency. Therefore, BLDC motors may be used in high-end white goods (refrigerators, washing machines, dishwashers, etc.), high-end pumps, fans, and other appliances that require high reliability and efficiency. The concept of the application is to create a speed-closed loop BLDC driver using a Hall position sensor. It serves as an example of a BLDC motor control system design using a Freescale microprocessor with the eTPU. It also


Purpose We present and validate a new methodology for analyzing, in an automated and objective fashion, infrared images of the meibomian glands (MG). Methods The developed algorithm consists of three main steps: selection of the region of interest, detection of MG, and analysis of MG morphometric parameters and dropout area (DOA). Additionally, a new approach to quantify the irregularity of MG is introduced. We recruited 149 adults from a general population. Infrared meibography, using Keratograph 5M, was performed. Images were assessed and graded subjectively (Meiboscore) by two experienced clinicians and objectively with the proposed automated method. Results The correlation of subjective DOA assessment between the two clinicians was poor and the average percentage of DOA estimated objectively for each Meiboscore group did not lie within their limits. The objective assessment showed lower variability of meibography grading than that obtained subjectively. Additionally, a new grading scale of MG DOA that reduces intraclass variation is proposed. Reported values of MG length and width were inversely proportional to the DOA. Gland irregularity was objectively quantified. Conclusions The proposed automatic and objective method provides accurate estimates of the DOA as well as additional morphologic parameters that could add valuable information in MG dysfunction understanding and diagnosis. Translational Relevance This approach highlights the shortcomings of currently used subjective methods, and provides the clinicians with an objective, quantitative and less variable alternative for assessing MG in a noninvasive and automated fashion. It provides a viable alternative to more time-consuming subjective methods.


Level - Intermediate. This tutorial assumes basic knowledge or experience with the Ada programming language.
 This tutorial covers two of the major problems with parallel and real-time programming - time management and storage management. Parallel processing, whether on single-processor machines or multiple processors, has many pitfalls. We will examine these potential pitfalls, and discuss ways to avoid common problems, such as deadlocks and race conditions. We will also discuss how to write code that efficiently passes data with other parallel processes. The basics of parallel processing are covered, leading to a discussion and examples using Ada tasking. In addition, the Ada Real-Time Systems Annex is also covered.


: The purpose of our systematic review is to document the adverse events that follow phacoemulsification in eyes with trabeculectomy due to glaucoma and to determine whether phacoemulsification jeopardizes the survival of the trabeculectomy. Our research was based on English- and non-English-language articles obtained using the Medline, Embase, Web of Science and Scopus databases. Additional studies were identified by searching bibliographies in the British Library and abstracts presented at the Association for Research in Vision and Ophthalmology annual meetings. Search terms included randomized controlled trial, controlled clinical trial, random allocation, double-blind method, matched studies and trabeculectomy failure, glaucoma-filtering operation failure, bleb failure and cataract surgery or phacoemulsification. Only prospective or retrospective matched studies testing the survival of a trabeculectomy alone versus clear corneal phacoemulsification after a trabeculectomy in patients with glaucoma were included. Data were independently extracted by two authors using predefined data fields. PubMed yielded 152 results, Scopus 235, Embase 222, and Web of Science (science citation index) 216. We read the abstracts of all the trials, and after reading the full text of 31 studies, we decided that 13 studies should be comprehensively evaluated. Current evidence does not allow us to draw safe conclusions on the scientific question so far.


Thousands of children with congenital heart disease are subjected to corrective surgery which involves stopping the heart and exposing it to ischemia reperfusion (IR) injury. Complications after cardiopulmonary bypass like low cardiac output can lead to inadequate organ perfusion and eventual organ dysfunction if not corrected in a timely manner. Newborn (2-4 days) hearts are more susceptible to ischemic injury than adult (>8 weeks) hearts as evidenced by their diminished ability to scavenge reactive oxygen species (ROS), specifically hydrogen peroxide (H2O2). Not only do newborn hearts exhibit decreased scavenging capability (compared to the adult) but they also contain reduced baseline levels of catalase (3.8 + 1.1 U/mg tissue in the LV and 4.3 + 2.3 U/mg tissue in the RV vs. 11.2 + 1.0 U/mg tissue in the adult LV and 11.6 + 0.3 U/mg tissue in the adult RV). We observed significantly increased levels of H2O2 in newborn rabbit myocytes following IR injury (4.3-fold vs 2.2 fold; p<0.05) that was not accompanied by an increase in catalase activity as was seen in the adult myocytes. The tyrosine kinase c-Abl was shown to play a role in regulating phosphyorylation (and activation) of catalase and we hypothesized this pathway may be dysregulated in newborns, leading to differences in catalase activity. We performed immunoprecipitation with c-Abl and catalase as well as Western analysis of whole heart homogenates in both newborn and adult samples (n=3). Results demonstrated an increase in catalase phosphorylation in adult but not newborn hearts after IR. In the newborn, preliminary studies displayed diminished phosphorylation of c-Abl, indicating a potential mechanism. In addition, catalase levels seem to acutely rise following IR, too early for new protein synthesis. Catalase is known to undergo ubiquitination following release from the c-Abl complex and this may play a role in the failure of newborns to increase catalase. Elucidation of this pathway will lead to a greater understanding of the mechanisms controlling catalase activity in the newborn versus the adult heart and will prove beneficial in developing therapeutic interventions to minimize damage following ischemic injury in newborns.


The paper attempts an explanation of the alleged "lack of adequate economic models" to predict and eventually avoid through certain policy recommendations the recurrent global or individual economic or financial and fiscal crises. In the author's opinion, in the controversy over the "rational expectation approach" and the design of dynamic and stochastic models, have been neglected some important underlying issues in economic performance, such as the very crucial institutional enforcement basis on which economic agents operate, including particularly government agents. The Public Choice School and modern Institutional Economics can help to understand the limitations and possibilities faced when seeking to improve the economic theory in its status as "science".


The objective of this research was to analyze the causes and consequences of the systematic process of teaching and learning of the division of whole numbers, a study aimed at students and teachers of the 3rd and 4th level of basic education. For its development the qualitative paradigm was used through the modality of field research. As informants, twenty (20) students and two (2) teachers participated. All participants are enrolled in the 3rd and 4th level of the Giordano Bruno School located in the city of Quito, Ecuador. To collect the information, the observation technique and the semi-structured interview were used, and the instruments were subjected to a validity process, where the triangulation was applied. The results were analyzed to give an answer to the proposed objective of the manuscript, where the teaching-learning method applied to the students is presented as a critical-constructivist model, but in reality, a mechanic-academicist education system is used. It was evidenced that teachers shorten the logical processes of the division of whole numbers, by the time-space factor.


The ever increasing number of sensor-equipped devices comes along with a growing need for data analysis techniques that are able to process time series streams in an online fashion. Although many sensorequipped devices produce never-ending data streams, most real-world applications merely require high-level information about the presence or absence of certain events that correspond to temporal patterns. Since online event detection is usually computational demanding, we propose a sliding window filter that decreases the time/space complexity and, therefore, allows edge computing on devices with only few resources. Our evaluation for online gesture recognition shows that the developed filtering approach does not only reduce the number of expensive dissimilarity comparison, but also maintains high precision.


The paper identifies some major economic, social and environmental effects of gaming-related tourism in Macau, the world's largest gaming location in respect of casino turnover. The main types of effects of casino development are typically those associated with growth machine theory. The paper also identifies major threats to the sustainable development of Macau as a gaming/tourism destination, arising from a narrow industrial base, competing destinations, community alienation, and what is referred to as the 'China factor'. The paper discusses the types of strategies that are required if Macau tourism is to counter these threats and develop successfully as a 'World Centre of Tourism and Leisure'. It is argued that Macau can most effectively achieve this goal if it develops its tourism and gaming industries to be consistent with the key attributes of a creative city.


Research trials conducted at two locations in the spring of 2004 evaluated the effect of soil temperature as an indicator for application timings of certain sulfonylurea herbicides for perennial ryegrass control while maintaining acceptable turfgrass quality during bermudagrass spring transition. Herbicide application timings began when soil temperatures reached 17 C (April 14, 2004). Greater perennial ryegrass control 4 wk after initial treatment (WAIT) was achieved when sulfonylurea herbicides were applied at 26 C soil temperature compared to 17 or 21 C. Bermudagrass density 6 WAIT increased with treatments applied at 26 C soil temperature compared to cooler soil temperatures. There was a decrease in overall turfgrass quality 2 WAIT when treatments were applied at 17 C. However, by 4 WAIT all application timings provided overall turfgrass quality comparable to the untreated control. Acceptable turfgrass quality and maximum perennial ryegrass control was achieved by delaying transition-aid herbicide applications until soil temperatures reached 26 C and growing conditions were more conducive to bermudagrass growth. Nomenclature: Chlorsulfuron, flazasulfuron, foramsulfuron, metsulfuron, rimsulfuron, trifloxysulfuron-sodium, perennial ryegrass, Lolium perenne L. LOLPE, common bermudagrass, Cynodon dactylon (L.) Pers. CYNDA, bermudagrass, Cynodon dactylon Pers. × transvaalensis Burtt-Davy 'Tifgreen'


Epidermal growth factor (EGF) attenuated hCG-stimulated adenylyl cyclase activity in rat luteal and follicular membranes. H7, an equipotent serine/threonine protein kinase inhibitor of cAMP-dependent protein kinases, cGMP-dependent protein kinases, and lipid-dependent protein kinase C, did not effect the ability of EGF to decrease hCG-responsive adenylyl cyclase activity, suggesting that a serine/threonine phosphorylation event catalyzed by these kinases was not critically involved in EGF-induced desensitization. Likewise, pertussis toxin-catalyzed ADP-ribosylation of a 40-kDa luteal membrane protein, which exhibited immunoreactivity with an antibody against Gi alpha, did not hinder the ability of EGF to attenuate hCG-stimulated adenylyl cyclase activity, indicating that Gi did not mediate EGF-induced desensitization. Rather, EGF-induced heterologous desensitization of LH/CG receptor in ovarian membranes was closely associated with the specific and prominent tyrosine phosphorylation of the 170-kDa EGF receptor. Both EGF-stimulated autophosphorylation of EGF receptor and EGF-induced LH/CG receptor desensitization were attenuated by genistein, a tyrosine kinase inhibitor. These results suggest that tyrosine phosphorylation of the 170-kDa EGF receptor is a necessary component of the signaling pathway in EGF-induced heterologous desensitization of the LH/CG receptor.


This article argues that the desire to promote a 'European way of life' constitutes a defining feature of contemporary European integration. What might be misinterpreted as an inward turn is in fact part of the temptation for the EU to become a 'civilizational state', one promoting a distinct identity against rival value systems. The analysis highlights the significance of the EU's ideological shift towards a civilizational narrative and explores the domestic and international factors pushing Brussels in this direction. The article also considers the practical consequences of the EU's attempt to act as a civilizational state in its foreign relations. Here the argument proceeds on the understanding that a civilization is not an essence but a set of practices associated with political decision-making, notably over boundaries. The EU response to Russian and Chinese attempts to extend their influence in Europe during the COVID-19 pandemic is examined as a case study of how more assertive boundary-making, to solidify the EU's civilizational claims, is likely to fuel geopolitical competition. Ultimately, the universal idea of Europe as a template for global governance was far less threatening for its systemic challengers. Hence the EU's pandemic response is a sign of heightened civilizational rivalry.
Civilizational state, EU foreign policy, COVID-19, Narratives, Pandemic


SummaryThis study examines the relationship between weight at birth and socio-economic influences in Vienna, Austraia between 1865 and 1930, a period of industrial development followed by economic collapse and subsequent recovery. A random sample of maternity patients from the major hospital in Vienna was selected. Most patients were of low social and economic status. All live, singleton infants weighing 1500 g or more were included in the study. Multiple regression analysis reveals that ethnicity, religion and marital status did not influence birth weight variations and that sex, maternal age and birth order were strongly correlated with variations in birth weight means. It further reveals that the socio-economic variables: occupation, season and year of birth, the length of a woman's stay in hospital prior to delivery and residential address were correlated with mean birth weight variations. Linear regression analysis suggests a moderately strong relationship between short-term fluctuations in the cost ...


For all the difference of the mechanisms underlying septic conditions encountered in otrohinolaryngological practice they have a common nature related to biological properties of the pathogen responsible for a given pathological process, primary localization of the lesioned structure, and anatomical characteristics of the affected region. These factors must be taken into consideration in planning surgical treatment,t antibacterial or pathogenetic therapy to manage septic processes in the ear, nose and/or throat. Such an approach may be instrumental in arresting the further extent of infection and thereby improving prognosis of the disease.


Bactec medium 9240 (Becton Dickinson, MD, USA) is a blood culture medium used routinely at Sultan Qaboos University Hospital (SQUH). The medium is said to contain substances that can neutralise antibiotics and destroy leucocytes in blood samples. In this study, the ability of the medium to neutralise the effect of some antibiotics and to destroy leucocytes is investigated. Vancomycin, amoxicillin, chloramphenicol, penicillin, gentamicin, fungizone and amikacin at various concentrations were added to separate bottles of Bactec medium 9240. Escherichia coli (NCTC 10418), Pseudomonas aeruginosa (NCTC 10662), Staphylococcus aureus (NCTC 6571) and Candida albicans (ATCC 10231), each at 1 x 10(4) colony-forming units (CFU)/mL were added separately, depending on the type of antibiotic. The blood samples were incubated at 37 degrees C for seven days under manual and automated blood culture systems. Subcultures were made from the manual system and routine laboratory procedures for detection of positive cultures were followed for the automated system. The Bactec medium was found to neutralise all antibiotics up to a concentration of 100 microg/mL by the automated method but showed some variation in results by the manual system. Leucocytes were destroyed within 24 hours.


Total Routhian surface (TRS) calculations for even–even N = 76 isotones with 54 ≤ Z ≤ 68 have been performed in three-dimensional (β2, γ, β4) deformation space. Calculated results of the equilibrium deformations are presented and compared with other theoretical predictions and available experimental data. The behavior of collective angular momentum shows the neutron rotation-alignment is preferred in the lighter N = 76 isotones, while for the heavier ones the proton alignment is favored. Moreover, multi-pair nucleon alignments and their competition (e.g., in 144Er) are predicted. It is pointed out that these nuclei in the N = 76 isotonic chain exhibit triaxiality or γ softness in high-spin states as well as ground states. Based on deformation-energy curves with respect to axial and non-axial quadrupole deformations, the shape instabilities are evaluated in detail and predicted, particularly in γ direction. Such instabilities are also supported by the odd- and even-spin level staggering of the observed γ bands, which is usually used to distinguish between γ-rigid and γ7-soft asymmetry.


Canada's aging population and intergenerational programs' ability to encourage active aging point to the need for further support and encouragement for these programs. The purpose of this case study was to explore and understand, from an insider's perspective, the lived experiences of six older adults who participated in an intergenerational project – Through Their Eyes. Three questions guided this inquiry: What are the experiences of older adults participating in the Through Their Eyes project? How did this experience influence their well-being? How did this experience influence their relationship to their community? I conducted critical qualitative research using semi-structured individual interviews, a focus group, a knowledge translation workshop, observations and field notes. The qualitative data were analyzed using constant comparative and inductive analysis techniques. Analysis highlighted 'opportunity' as the central theme of the study. During a time in older adults' lives when they are experiencing many losses, the Through Their Eyes project was an opportunity for gain. Specifically, the intergenerational project provided an opportunity for new relationships. There was a familial-type intimacy to the relationships older adults develop with students as participants' often compared their student interviewers to their grandchildren. The Through Their Eyes project also offered a space and place for older adults to be heard regarding their community. Older adults wanted the information they provided for the project to help other aging adults in their community. Finally the intergenerational project added a joyful memory and experience for participants. When participants shared their thoughts on the Through Their Eyes project, it was clear that it was a joyful experience as all of them describe it as such. Findings illustrated that the Through Their Eyes project encouraged active aging and enhanced quality of life for participants by providing an opportunity for social participation and allowing them to remain active and engaged citizens. The Through Their Eyes project fostered social participation by establishing connections between generations, addressing social isolation and loneliness, and breaking down stereotypes and age barriers. The Through Their Eyes project allowed older adults to remain active and engaged citizens in their neighbourhoods by providing an important opportunity for reciprocity and a place for them to be listened to in regards to their community matters. Insights into practical implications based on the findings from this study and suggestions for future research in the area of intergenerational programs are identified. *


In this two-part paper, a design methodology for hardware reduction in digital delta-sigma modulators (DDSMs) based on bus-splitting and error masking is presented. Part I addresses Multi stAge noise SHaping (MASH) DDSMs with constant inputs; Part II focuses on error feedback modulators (EFMs) with time-varying inputs. In this paper, we address EFMs with DC inputs plus additive input least significant bit (LSB) dithering and show how hardware reduction can be achieved with minimal degradation of the output spectrum. We also address EFMs with sinusoidal inputs and show how bus-splitting and error masking techniques can be used to obtain a trade-off between the modulator complexity and the achievable signal-to-noise ratio.


The growth of the online market lately is very rapid due to the World Wide Web. Many crowdfunding-based companies are helping creative projects grow rapidly. To measure the success of a project based solely on the percentage of fundraising cannot represent the favourite market of the desired product backers. In this study, the measure of success is judged by the ratio of the funding amount and the ratio of the product amount in the period of time. After this, there are 4 quadrants that determine the success of the product including: moderate favourite markets (quadrant I), the most favourite markets (quadrant II), not favourite markets (quadrant III), and moderate favourite markets (quadrant IV). Eight companies start-up with 68 selected 3D Printer products in this study. The results show that no single product is in "favourite market". 63 products are in "non-favourite markets". There are only 5 projects in the market "moderate favourites".


– The purpose of this study was to compare Social Adjustment between physical education and non-physical education students. The study was performed with randomly selected 30 male subjects from Physical Education students and 30 male subjects of Non-Physical Education students of age range 17 to 23 years old of Chaudhary Charan Singh University, Meerut. The study was also delimited to assessment of Social Adjustment by using Social Adjustment questionnaire of Assistant Index of Cowell's. The significant difference of Social Adjustment between physical education students and non-physical education students was 7.27, which is higher than the required value at 0.05 level of significance (t=2.00). It shows there is significant difference between the performance of physical education and non-physical education subjects on social adjustment.


This paper addresses the challenges of implementing transportation projects and policies. Despite advances in data, analysis tools, and technologies, the difficulty of making the case remains for transportation actions where the values of those actions are perceived by key stakeholders as less than commensurate with the costs that they are asked to pay. This perceived inequity occurs when citizens who bear the impacts of transportation actions are not the beneficiaries, when the benefits are characterized in aggregate, and when projects do not appear to be salient to the majority of stakeholders. In such cases, there is a need to construct a more explicit value proposition, a statement of promised results that fosters belief on the part of stakeholders. Promised results should be presented in credible forecasts of outcomes from actions that improve transportation performance. They should be described in terms that are specific enough to address the what's-in-it-for-me question. And they should be built on agency credibility earned by a record of delivering results. Freight projects are particularly difficult to advance because the economic and social benefits of freight performance are largely invisible to citizens, underscoring the need to make the value proposition for freight project outcomes relevant to individuals and communities. The relationships between transportation investments and their outcomes, the quality of forecasting tools, and the credibility of transportation agencies can be advanced through systematic, balanced, post-project audits (including before–after evaluations) to learn and to demonstrate the actualized value of transportation projects and policies. These ideas are entirely consistent with, and supportive of, the concepts of performance-based management advanced under MAP-21.


Background: Hypoxia in tumors is associated with malignant progression, metastatic spread, and increased resistance to radiotherapy and chemotherapy. Molecular O2 is required for the cellular production of nitric oxide (NO) by the enzyme NO synthase (NOS), and NO may block components of the adaptive response to hypoxia. Hence, we hypothesized that hypoxia increases drug resistance in tumor cells by inhibiting endogenous NO production. Methods: Human breast carcinoma (MDA-MB-231) and mouse melanoma (B16F10) cells were preexposed to 20% O2 ,5 % O 2 ,o r 1% O 2, incubated with a pharmacologic inhibitor of endogenous NO production, and then treated with chemotherapeutic agents. Resistance was assessed by colony-formation assays, and western blot analysis was used to measure NOS protein levels. All P values were twosided. Results: Incubation of MDAMB-231 tumor cells in 1% O2 maximally increased their resistance to doxorubicin and 5-fluorouracil by 8.5fold (P = .002) and 2.3-fold (P = .002), respectively, compared with incubation in 20% O2. B16F10 mouse melanoma cells preincubated in 1% O2 (versus 20% O2) for 12 hours exhibited a twofold increase in resistance to doxorubicin (P<.001). The rapid acquisition of drug resistance after exposure to 1% O2 could be mimicked by incubating the MDA-MB-231 cells for 12 hours with the NOS inhibitor N G -monomethyl-Larginine (fivefold increase; P<.001). Conversely, replacement of NO activity by use of the NO-mimetic glyceryl trinitrate (GTN) and diethylenetriamine NO adduct produced statistically significant attenuations in the development of resistance of 59% (P<.001) and 40% (P<.001), respectively, in MDA-MB-231 cells. Treatment of B16F10 cells with GTN produced a 58% reduction in resistance (P<.001). MDA-MB-231 cells expressed all three


In this work the total quality management (TQM) and Kaizen philosophies were applied on the electricity and public water sector maintenance. The methodology of collecting the data was by designing a special questionnaire containing a series of questions comparing these two philosophies for a specific period of application to study their effect on the maintenance and the cost in the electricity and public water sector. After six months of applying these philosophies, the questionnaire data were collected and analyzed using SPSS package. The results have shown that 55% of employees believe that the philosophy of kaizen is relatively applied in the electricity sector. But there is a ratio of 65% of them think that the administration of the total quality management is the most suitable to be applied in the electricity and water sectors. In addition to that there is a ratio of about 50% see that both methods have achieved better improvements of maintenance in comparison with traditional methods, consequently both methods were successful in the electricity sector for improving maintenance and reducing the cost. But the results were almost equal and this may indicate that due to the lack of sufficient knowledge of the pros and cons of both ways.


In the following paper, I put forth a claim that literary works created according to the rules of conceptualism, seemingly devoid of expression, often reveal that values are inseparable from any textual operations. This is visible in Kenneth Goldsmith's recent project, "The Body of Michael Brown," which follows the format of Goldsmith's previous book-Seven American Deaths and Disasters-a transcription of news reports of American national disasters, such as the assassination of John F. Kennedy or the attacks of 9/11. The text rewrites the autopsy report issued by the St. Louis County Coroner's Office on the shooting of Michael Brown, an African-American teenager shot and killed by a white police officer in Ferguson, Missouri. The problem with the new conceptual art practice is that it disregards the ethical dimension of creation. For Goldsmith, ethical issues in art are limited to the question of "faithful" copying/rewriting, regardless of the fact that an appropriated text always reflects editorial manipulation and politics behind it. Goldsmith thinks of himself as a daring disciple of Duchamp, but he fails to understand that his text propagates racist violence, performing anew the autopsy's latent, institutional racism. In terms of methodology, I rely in my analyses on Marjorie Perloff's understanding of the concept of avant-garde and refer to the theories about literature and ethics emerging from recent writings by Cathy Park Hong and Jacques Ranciére.


: The use of upper gastrointestinal endoscopy (UGE) for diagnosis and treatment is becoming increasingly more frequent in children. Unlike adults, children require deep sedation. The effects of ketamine, one of the most commonly used agents in UGE of children, are rapid, but short; ketamine offers quick recovery and has wide confidence intervals. The basic aim of this review is to explain the Ketamine efficacy during endoscopy in adult patients. Ketamine is a general anaesthetic agent widely used for paediatric procedural sedation outside the operating theatre by non-anesthesiologists. It is considered a dissociative anaesthetic. Endoscopy is the most accurate and beneficial way for the diagnosis of dyspepsia, peptic ulcers, and malignancies. Sedative drugs are used for both patient and physician satisfaction during the procedure; type of endoscopy, duration, degree of difficulty, and patients' physical status are the criteria which determine the suitable type of sedation for endoscopy. It is concluded from the literature and previously published data low-dose oral administration of ketamine could make a suitable sedation for gastro-enteric endoscopy.


With modern optimization techniques it is generally possible to form some kind of image estimate using an arbitrary collection of views or sensor measurements of an unknown object. The question is what is the best result that one can get with that data and will it be acceptable? We use optimization theory to analyze inverse problems such as this and formulate strategies for understanding how much high resolution information is contained in the data and how to intelligently reconstruct the best image possible. We start by formulating the reconstruction problem for a variety of different imaging systems, which we can view as special cases or extensions of tomography. In order to understand the range of potential solutions to such inverse problems, we formulate the optimization problems of bounding the elements of the unknown. We proceed to develop a novel approach to investigating inverse problems by defining uniqueness as the case where the upper and lower bounds on possible values each element can take are equal. This allows us both to express uniqueness on an element-wise basis, e.g. some elements may be uniquely-reconstructed while others may not, and to formulate conditions for uniqueness. These conditions provide a generalization of known conditions for unique solutions to systems with sparse or non-negative unknowns. We use these uniqueness conditions to pose a novel approach to estimation of system resolution and to thereby find low-resolution approximations which provide as much resolution as possible while retaining the uniqueness of the solution. Finally we demonstrate the extension to noisy and regularized problems using a Bayesian formulation which allows us to form trade-offs between resolution and uncertainty


Realizing the full potential of a multi-radio mesh network involves two main challenges: how to assign channels to radios at each node to minimize interference and how to choose high throughput routing paths in the face of lossy links, variable channel conditions and external load. This paper presents ROMA, a practical, distributed channel assignment and routing protocol that achieves good multi-hop path performance between every node and one or more designated gateway nodes in a dual-radio network. ROMA assigns nonoverlapping channels to links along each gateway path to eliminate intra-path interference. ROMA reduces inter-path interference by assigning different channels to paths destined for different gateways whenever possible. Evaluations on a 24-node dual-radio testbed show that ROMA achieves high throughput in a variety of scenarios. This project was led by Aditya Dhananjay, whose publication record is below [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16].


Both gastrointestinal symptoms and fecal shedding of SARS-CoV-2 RNA have been frequently observed in COVID-19 patients. However, whether SARS-CoV-2 replicate in the human intestine and its clinical relevance to potential fecal-oral transmission remain unclear. Here, we demonstrate productive infection of SARS-CoV-2 in ACE2+ mature enterocytes in human small intestinal enteroids. In addition to TMPRSS2, another mucosa-specific serine protease, TMPRSS4, also enhanced SARS-CoV-2 spike fusogenic activity and mediated viral entry into host cells. However, newly synthesized viruses released into the intestinal lumen were rapidly inactivated by human colonic fluids and no infectious virus was recovered from the stool specimens of COVID-19 patients. Our results highlight the intestine as a potential site of SARS-CoV-2 replication, which may contribute to local and systemic illness and overall disease progression.


We consider the channel estimation of a time-slotted wireless communication system with a mobile user and a base station, where the base station employs an M-element (M >; 1) antenna array. The uplink single-input multiple-output (SIMO) channel is usually estimated by training sequence within each time slot. To improve the estimation performance, the channel estimate is often refined by projecting it to the corresponding spatial signal subspace. However, this projection will not work when the number of resolvable multipath rays is larger than that of the antenna array elements, which makes the channel matrix full row rank. In this paper, we formulate the channel estimation under the space-time signal model for this full-row-rank case, and propose a new method by space-time signal subspace projection using both training and unknown data sequences. To further improve the accuracy of the channel estimate, the soft information fed back from the decoder can be used. By involving this soft information, we propose another new channel estimation method. This method approximately follows the maximum likelihood (ML) criterion and is therefore referred to as the approximated ML channel estimation. Numerical results show that these methods can be performed separately or jointly to improve the performance of channel estimation by training sequences.


The Johannesburg bouncer mafia, a series of violent and competing groups, dominated the city's underworld from the late 1980s until the early 2000s. While the bouncer mafia was one of several emerging criminal networks at the time, although the most prominent in respect of Johannesburg's changing illicit drug economy, they provide a useful example of how organised crime originated during South Africa's transition: a fact often commented on, but little understood. A study of the bouncer mafia may yield important conclusions for the rise and fall of criminal groups. Informed by the experience of members themselves, this account provides an opportunity to study the conditions under which organised crime groups take root during periods of political, economic and social transition, including how such groups recruit, consolidate, compete and how they may decline and be replaced. The narrative is told in three phases, their growth, consolidation, transition and decline. The Johannesburg bouncer mafia was born out of a set of tough, white, working-class boxing and sports clubs in Hillbrow and south and east Johannesburg. Sharing a background of apartheid-era military service, the bouncers evolved from independent 'heavies' into a set of registered private security companies competing for turf and control of the illicit drug trade. Changes in the prevailing political and socio-economic environment of the country during the transition to democracy were reflected in structural changes in the city's night-time economy; this led to the consolidation of the bouncer mafia, which, by early 2000, had concentrated into one company, Elite, assuming almost complete control of protection of the drug trade in clubs. A series of prevalent factors and changes in the industry precipitated the dramatic decline of the bouncer mafia: socio-economic transition altered not only the racial profile of key areas, but also the face of policing, resulting in a weakening of the networks between bouncers and the police. The increasing recruitment of African bouncers by clubs themselves – primarily from Congo and Nigeria, they were cheaper than their white counterparts, more easily available when the former white bouncer recruitment networks dried up, and less prone to violence – facilitated a shift in control of the city's drug trade to Nigerian criminal networks, thereby laying the foundation for a critical component of modern organised crime in Johannesburg.


Ceramic solid solutions Bi4MnxV2–xO11–(x/2)–δ in the composition range 0.07 ≤ x ≤ 0.30 were obtained by solid state synthesis. Structural investigations were carried out by using a combination of FT-IR and powder X-ray diffraction technique. Polymorphic transitions (β↔γ and γ′↔γ) were detected by DTA and variation in the Arrhenius plots of conductivity. The solid solutions with composition 0.07 ≤ x ≤ 0.17 are isostructural with the orthorhombic β-phase, and those with x ≤ 0.30 represent tetragonal γ-phase. With increasing Mn concentration, the conductivity of solid solutions increases from 3.684×10-6 (x = 0.07) to 2.467×10-5 (x = 0.17). AC impedance plots show that the conductivity is mainly due to the grain contribution which is evident in the enhanced short range diffusion of oxide ion vacancy in the grains with increasing temperature.


Summary: The isolation and identification of cytoplasmic membranes from cyanobacteria is complicated by the presence of multiple photosynthetic membranes (thylakoids), and by a lack of biochemical markers characteristic of the cytoplasmic membranes of heterotrophic pro-karyotes. [3H]Benzylpenicillin was used to label the penicillin-binding proteins (PBPs) in the unicellular cyanobacterium Synechococcus sp. strain R2 (PCC 7942), in spheroplasts and in fractionated cell membranes. Spheroplasts were made with lysozyme/EDTA, and were broken by shaking with glass beads in hypo-osmotic buffer at 4 °C. Sequential glycerol density gradients were then used to purify the membrane fractions. A low-density membrane (LDM) fraction was isolated which, when compared to the thylakoid fraction, was enriched in a unique carotenoid with an absorption maximum at 390 nm and low in chlorophyll a absorption at 678 nm (A
390/A
678 > 10). This fraction had a characteristic polypeptide profile on denaturing polyacrylamide gels (SDS-PAGE), and specific enrichment of PBPs, as detected by fluorography of membrane fractions incubated with [3H]benzylpenicillin followed by SDS-PAGE. The M
r values of the Synechococcus PBPs differed from those in Staphylococcus aureus or Escherichia coli membranes. The high content of specific PBPs in LDM suggested that this fraction was highly enriched in cytoplasmic membrane. A membrane fraction with density between that of the thylakoid and LDM fractions, previously considered to be a mixture of these membranes, showed specific enrichment of a PBP of M
r 78000. This fraction may contain contact zones between the different membrane types.


Micro-architectural analysis (MA) is a fast evolving area of side-channel cryptanalysis. This new area focuses on the effects of common processor components and their functionalities on the security of software cryptosystems. The main characteristic of micro-architectural attacks, which sets them aside from classical side-channel attacks, is the simple fact that they exploit the micro-architectural behavior of modern computer systems. Attackers could get running information through malicious software, then get some sensitive information through off-line analysis. This kind of attack has the following features: 1.) side channel information are acquired through software measurement on target machine with no need to use sophisticated devices. 2.) non-privilege process could get the running information of the privilege process. 3.) people can mount both a remote attack and local attack. This thesis mainly focuses one kinds of these attacks, data cache based timing attacks(CBTA). First, the main principle of CBTA is introduced, and several kinds of CBTA technique are discussed. Moreover, theoretical model is given under some attacks. Second, various countermeasures are described and their advantages and disadvantages are pointed out. Based on these discussions, the author proposes two anti-attack measures using hardware modification. Aiming at access-driven attacks, a XOR address remapping technique is proposed, which could obfuscate the mapping relationship between cache line and memory block. Aiming at timing-driven attacks, the IPMG mechanism is proposed innovatively. This mechanism could generate cache miss dynamically through observing the historic miss rate. These two mechanisms are realized on the MIPS processor and their effectiveness is verified on the FPGA board. At last, performance penalty and hardware cost are evaluated. The result shows that the proposed solution is effective with very low performance penalty and area cost


In this paper we present different order statistics filters in the Wavelet domain for noise suppression in color image processing. All proposed filters are defined as two filters in the wavelet domain: the first filter is based on redundancy of approaches and the second one is the wavelet domain iterative center weighted median algorithm. With this structure different implementations for the estimation of the noisy sample are already carried out using different order statistics algorithms.


A hierarchical evolutionary trajectory planner (HETP) for spacecraft formation reconfiguration is presented. Two levels are included in HETP. The high-level planner performs global planning which includes configuration optimization and collision avoidance between spacecraft. The low-level planners design multiple optimal or near optimal trajectories which are separated one from another for each spacecraft by parameterizing the controls in terms of Chebyshev polynomials. Based on the attributes of the system dynamics, a flexible scheme is used to select final trajectories and to avoid collisions. Our approach scales well with the number of spacecraft by planning trajectories for each spacecraft in parallel. The high level and the low level can coevolve, and multiple trajectories can be generated simultaneously as alternatives. The control precision constraints which could reduce control errors are also taken into account. The experiments described here demonstrate the efficiency of the proposed algorithm.


Neurologists are medical doctors that diagnose and treat disorders and diseases of the central and peripheral nervous systems. Knowledge of the entire body is critical to these physicians. They treat a wide variety of conditions ranging from mental disorders to coordination problems to problems with the senses. Neurological tests provide these doctors with the necessary information to make diagnoses.


A proprioceptive mechanism of vehicle driving simulator is proposed to realize pitch, roll and vibration action of vehicle driving simulator based on application foundation of proprioceptive mechanism. The proposed mechanism has very simple structure and a brief description of this mechanism is given. The proposed proprioceptive mechanism is established based on CATIA V5 platform by using the virtual prototyping technology. The CATIA V5 motion simulation model is used to simulate the proposed proprioceptive mechanism by setting the parameters of source motion input and motion interference and motion characteristic is analyzed to provide design basis. The kinematics simulation results show that the designed proprioceptive mechanism for vehicle driving simulator can realize the design requirements and complete the proprioceptive actions.


With the development of network, multimedia will be the main application in next generation network. Voice is one of the most important applications. Recently a kind of P2P-based VoIP software, Skype, has been receiving more and more attention both in academia and industry. Skype claims that it's better than other VoIP software, because of its high call completion rate and superior sound quality. This paper will reveal Skype's technique and have a performance comparison between Skype and MSN Messenger, which uses traditional VoIP protocol. The result indicates that the voice quality of Skype is no better than traditional VoIP software and the great benefit of P2P involved with VoIP is that it can solve NAT and firewall problems.


Optimizing energy consumption is the main concern for designing and planning the operation of the Wireless Sensor Networks (WSNs). Clustering technique is one of the methods utilized to extend lifetime of the network and balancing energy consumption among sensor nodes of the network. In this paper, we propose the recently developed, heuristic optimization algorithms like Particle Swarm Optimization (PSO) and Tabu Search Algorithm(TSA) as well as the traditional Fuzzy C-Means (FCM) clustering algorithms. A comparison is made with the well known cluster-based protocol approach developed for WSNs known as harmony search algorithm which is music based Meta heuristic optimization method. Simulation results demonstrate that the proposed protocol using hybrid can reduce energy consumption and improve the network lifetime.


More and more consumers are searching the Internet for health information. Health Web sites vary in quality, though, and not all consumers are aware of the need to evaluate the information they find on the Web. Nurses and other health providers involved in patient education can evaluate Web sites and suggest quality sites for patients to use. This article describes a project we implemented in 2 public libraries to educate consumers about quality health care and patient safety using Web sites that we had evaluated earlier. Participants (n = 103) completed resources on health care quality, questions patients should ask about their diagnoses and treatment options, changes in Medicare and Medicare options or ways to make their health benefits work for them, and tips to help prevent medical errors. Most consumers were highly satisfied with the Web sites and the information they learned on quality care from these resources. Many participants did not have Internet access at home or work and instead used the library to search the Web. Information about the Web sites used in this project and other sites on quality care can be made available in libraries and community settings and as part of patient education resources in hospitals. The Web provides easy access for consumers to information about patient safety initiatives and health care quality in general.


Authors must provide a brief abstract. References: American Medical Association style. See the following examples: 1.Jones J. Necrotizing Candida esophagitis. JAMA. 1980;244:2190-2191. 2. Stryer L. Biochemistry. 2nd ed. San Francisco, Calif: WH Freeman Co; 1980:559-596. Continuing Medical Education: Authors must submit four multiple-choice questions (two Type A and two Type K), with answers. Copyright: Materials are accepted for exclusive publication in CNS Spectrums and become the property of CNS Spectrums. Permission to reproduce material must be obtained from the publisher. Disclosure of Commercial Interests Authors must include a statement about all forms of support, including grant and drug company support. Such information may, at the editor's discretion, be shared with reviewers. If the article is accepted for publication, the editors will consult with the authors as to whether this information should be included in the published paper. Submission Checklist • Original manuscript plus one copy, with cover letter on author's letterhead Q Copies of permission letters to reproduce previously published and unpublished material Ll A brief abstract of the article • Four CME multiple-choice questions with answers • Disk labeled with the word processing program, title of paper, and lead author's name J Names and addresses of five potential reviewers MBL Communications Directory of Services GUIDE TO DSM-IV AND ICD-10 CODES


With the advent of flexible electronics, flexible lithium-ion batteries have attracted great attention as a promising power source in the emerging field of flexible and wearable electronic devices such as roll-up displays, touch screens, conformable active radio-frequency identification tags, wearable sensors and implantable medical devices. In this review, we summarize the recent research progress of flexible lithium-ion batteries, with special emphasis on electrode material selectivity and battery structural design. We begin with a brief introduction of flexible lithium-ion batteries and the current development of flexible solid-state electrolytes for applications in this field. This is followed by a detailed overview of the recent progress on flexible electrode materials based on carbon nanotubes, graphene, carbon cloth, conductive paper (cellulose), textiles and some other low-dimensional nanostructured materials. Then recently proposed prototypes of flexible cable/wire type, transparent and stretchable lithium-ion batteries are highlighted. The latest advances in the exploration of other flexible battery systems such as lithium–sulfur, Zn–C (MnO2) and sodium-ion batteries, as well as related electrode materials are included. Finally, the prospects and challenges toward the practical uses of flexible lithium-ion batteries in electronic devices are discussed.


The theoretical inquiry into the foundations of criminal law in the twentieth century, in both civil and common law traditions, is assayed by the consideration of seven main currents or trends. First, the structure of offenses is examined in light of the bipartite, tripartite, and quadripartite modes of analysis. Second, competing theories of culpability - normative and descriptive - are weighed in connection with their important ramifications for the presumption of proof and the allocation of the burden of persuasion on defenses. Third, the struggle with alternatives to punishment for the control and commitment of dangerous but non-criminal persons is compared in civil and common law approaches. Fourth, the ascendancy of feminism, as the most successful interdisciplinary school of thought applied to criminal law since the early 1970s, and its contributions in the areas of rape, self-defense, provocation, and capital punishment are charted and weighed. Fifth, one of the most distinctive facets of criminal theory in the last century has been the emergence of the victims' rights movement; its success is compared in civil and common law jurisdictions. Sixth, while it is commonplace in the civil law tradition to embed issues of criminal law within the principles of constitutional law, common law jurisdictions vary; the increasing constitutionalization of criminal law in Canada is contrasted with its decrease in the U.S. Seventh, against the backdrop of a particularly intense period of codification of the criminal law in the last half of the twentieth century, the celebrated American Model Penal Code is criticized. Finally, four predictions for the direction of criminal theory in the next century are ventured.


This study assessed the contribution of training and compensation in financial institutions in Tanzania. The general purpose of the study was to assess the contribution of training and compensation management in improving employee performance in financial institutions like NMB PLC. Specifically the study aimed to analyze the contribution of training and compensation to employee performance particularly in NMB PLC, to find out the effect of which training and compensation management can be used as a tool for improving organizational performance to both employees' and employers' and to determine the relationships between training and organization performance in financial institutions like NMB in Tanzania as a case study The pursuance of the objective of the study, descriptive survey design was adopted. Pearson's Product Moment Correlation was used to test the significance of the coefficient of correlation at 5% level of significant.

It was found that training and compensation for employees in financial institutions has a significant effect on their performance and that financial compensation received are commensurate with employees' efforts. The study more found that training and compensation have significant effect in organization performance to both employee and employers. However it found that there is significant relationship between on job-training and organization performance.

Based on these findings, it is recommended that for any financial institution such as NMB PLC to improve the performance of employees', they should offer training and other forms of compensation that will specifically designed to link it with performance.


Objectives: The first trimester combined test based on measurements of fetal nuchal translucency (NT), maternal serum free β-hCG (fbhCG) and PAPP-A is currently the standard tool for aneuploidy screening. The aim of this study is to investigate how fetal sex influences these parameters. Methods: We examined the first trimester delta-NT (mm), fbHCG (MoM) and PAPP-A (MoM) in 8911 normal singleton pregnancies of known fetal sex determined by the means of second trimester ultrasound. Further similar analyses were carried out in 116 pregnancies with trisomy 21 and in 43 pregnancies with trisomy 18 with fetal sex known from karyotyping. Medians of these parameters were calculated for male and female fetuses and groups were compared using non-parametric Mann-Whitney U test. Results: In normal pregnancies the median of delta-NTs of female fetuses was by 0.029 mm lower, the median of PAPP-A was by 0.06 MoM higher and of fbhCG was by 0.20 MoM higher compared to male fetuses. The differences in all these cases reached statistical significance (P < 0.0001). Pregnancies with Down syndrome showed the median of delta-NTs of female fetuses lower by 0.15 mm, the median of PAPP-A and fbhCG higher by 0.195 MoM and 0.475 MoM respectively in comparison with male fetuses. Finally, in trisomy 18 pregnancies we observed female median of delta-NTs lower by 1.62 mm, PAPP-A higher by 0.13 MoM and fbhCG lower by 0.08 MoM in contrast to male fetuses. However, the differences in pregnancies with trisomy 21 and trisomy 18 did not reach statistical significance of 5%. Conclusions: We have found that fetal sex influences the measured parameters of the first trimester combined test. Correcting for fetal sex remains the matter of further discussion. However, although the results in normal pregnancies reached statistical significance, e.g. the difference in delta-NT medians of 0.029 mm seems well below the current feasible precision of NT measurement. OP18.02 Improving the detection rate in first trimester screening for chromosomal abnormalities: using a 1 in 300 vs. a 1 in 100 risk assessment cut-off point


Dutch corporate law is generally perceived to be based upon the stakeholder value model. According to this model, a company's management board has to consider the interests of the stakeholders affiliated with the company in determining the company's strategy and actions. In this respect, the notion of 'stakeholder' may include a broad range of groups and individuals. Importantly, these groups and individuals do not necessarily form part of the company's formal internal decision-making processes; for example, the stakeholder notion may also cover lenders, suppliers, customers and NGO's.

Although Dutch corporate law thus mandates board members to consider stakeholder interests, it does not prescribe - nor does it include best practices or principles for - formal and proactive stakeholder engagement. It has been argued that organizing an active stakeholder dialogue is the only - or at least most effective - way to assess the impact of a company's activities on external stakeholder groups and thus for a management board to be able to actually consider their interests. This paper aims to stir up the discussion on this topic and to introduce two structures under Dutch corporate law for a company to set up formal stakeholder engagement.

The paper starts by summarizing the theory on the basis of which active stakeholder participation in corporate governance is propagated in extant literature. Subsequently, it provides an outline of the corporate governance structure of companies incorporated under Dutch law, followed by a description of the aforementioned two structures for a company to set up a formal stakeholder engagement under Dutch law: the "stakeholder council" and the "priority foundation". The former is best suited to serve as a discussion platform for the management board, whereas the latter can be equipped with more far-reaching decision-making powers in a company's governance, allowing the company to take the stakeholder dialogue even further.


To elucidate physiological and clinical implications of the natriuretic peptide family, the expression of receptors for natriuretic peptides has been examined in cultured cells (a rat pheochromocytoma cell line [PC12], bovine endothelial cells, rat aortic smooth muscle cells, human mesangial cells, and a porcine kidney epithelial cell line [LLC-PK1]) by Northern blot analysis and cyclic GMP production method for the ANP-A and ANP-B receptors and by Northern blot analysis and binding assay for the clearance receptor. The ANP-A receptor was predominantly expressed in PC12 cells, bovine endothelial cells, and LLC-PK, cells but was barely expressed in rat aortic smooth muscle cells and human mesangial cells. By contrast, the ANP-B receptor was the major subtype of the biologically active receptors in rat aortic smooth muscle cells and human mesangial cells. Only a small amount of the ANP-B receptor was detected in PC12 cells, bovine endothelial cells, and LLC-PK, cells. The clearance receptor was abundantly expressed in rat aortic smooth muscle cells and human mesangial cells and was also present in bovine endothelial cells, but it was undetectable in PC12 cells and LLC-PK1 cells. These results demonstrate that the expression of three natriuretic peptide receptors varies from cell to cell, which is relevant to cell- or tissue-specific action of the natriuretic peptide family.


This article examines how far, and in what ways, overseas systems of worker representation are influencing the Australian debate. After briefly exploring the diminution of legal support for worker representation over the last 15 years, the article contains a detailed analysis and comparison of recent policy proposals put forward by the Australian Council of Trade Unions and the Federal Labor Opposition. The ACTU policy draws heavily on the United States, Canadian and United Kingdom collective bargaining and union recognition systems, along with North American and (particularly) New Zealand concepts of 'good faith bargaining'. Key aspects of these overseas systems are highlighted. In contrast, the ALP industrial relations policy is a substantially diluted version of the ACTU blueprint, involving only minimal 'borrowing' from overseas worker representation laws. Importantly, stronger supports for collective bargaining - such as the NZ mechanism for arbitration of bargaining impasses - have been omitted from Labor's policy. If implemented, this would see the emergence in Australia of a blend of several overseas worker representation models, resulting in some improvement to the current legal framework's subversion of collective bargaining - but not to the extent desired by the ACTU.


Recently we have studied the secretion pattern of a pectin methylesterase inhibitor protein (PMEI1) and a polygalacturonase inhibitor protein (PGIP2) in tobacco protoplast using the protein fusions, secGFP-PMEI1 and PGIP2-GFP. Both chimeras reach the cell wall by passing through the endomembrane system but using distinct mechanisms and through a pathway distinguishable from the default sorting of a secreted GFP. After reaching the apoplast, secGFP-PMEI1 is stably accumulated in the cell wall, while PGIP2-GFP undergoes endocytic trafficking. Here we describe the final localization of PGIP2-GFP in the vacuole, evidenced by co-localization with the marker Aleu-RFP, and show a graphic elaboration of its sorting pattern. A working model taking into consideration the presence of a regulated apoplast-targeted secretion pathway is proposed.


Introduction Distinguishing biliary tract cancer (BTC: cholangiocarcinoma and gallbladder carcinoma) from benign biliary disease such as pre-malignant primary sclerosing cholangitis (PSC) or immunoglobulin G4-associated cholangitis (IAC) can be difficult. Serum markers such as CA19.9 and immunoglobulin G4 lack sensitivity and specificity. There is a need for better biomarkers to differentiate these clinically similar diseases. We aimed to perform serum immunoaffinity depletion, 2-dimensional difference gel electrophoresis (2-DIGE) and liquid chromatography tandem mass spectrometry to identify differential biomarkers in benign and malignant biliary disease and healthy volunteers. Methods Blood was prospectively collected from 37 patients with BTC, 11 with PSC, 7 with IAC and 30 healthy volunteers. Serum was pooled into the four clinical groups and immunoaffinity depleted via fast protein liquid chromatography to remove highly abundant proteins. Following 2-DIGE using minimal labelling Cy-dyes, gels were scanned then analysed with DeCyder software. Protein spots with a >2-fold differential expression (p<0.01, Student t test) were picked, trypsin digested and subjected to nanoflow reversed-phase liquid chromatography coupled to electrospray ionisation tandem mass spectrometry for protein identification. Results The median age of BTC, PSC, IAC and healthy groups were similar at 68 (range 27–93), 47 (range 22–76), 63 (range 43–71) and 64 (range 40–79) years, respectively. The median serum bilirubin in the BTC, PSC and IAC groups was 40 (range 8–616), 20 (range 7–457) and 12 (range 5–40) μmol/l, respectively. 30/37 BTC, 4/11 PSC and 1/4 IAC patients, had elevated (>37 IU/ml) CA 19.9 levels. 61 protein spots were picked, of which 34 were upregulated and 13 downregulated in BTC vs healthy, 32 upregulated and 9 downregulated in BTC vs PSC, and 7 upregulated and 12 downregulated in PSC vs IAC. Leucine-rich glycoprotein, apolipoprotein A-IV and E, MASP2, CLEC3B, RAD1 and vimentin were upregulated and Hsp90, C4BPA and SERPIND1 downregulated in BTC vs PSC. Carbonic anhydrase 1, lumican and twinfilin-2 were upregulated and IgG4 chain C region and MASP2 were downregulated in PSC vs IAC, respectively. Serum validation of putative markers is underway. Conclusion Differentially expressed serum proteins in benign and malignant biliary disease were identified using this proteomic approach. These putative markers may be useful in monitoring patients with PSC who are at increased risk of BTC.


Currently, the development of high-integrity embedded component-based software systems is not supported by well-integrated means allowing for quality evaluation and design support within a development process. Quality, especially dependability, is very important for such systems. The CHESS (Composition with Guarantees for High-integrity Embedded Software Components Assembly) project aims at providing a new systems development methodology to capture extra-functional concerns and extend Model Driven Engineering industrial practices and technology approaches to specifically address the architectural structure, the interactions and the behavior of system components while guaranteeing their correctness and the level of service at run time. The CHESS methodology is expected to be supported by a tool-set which consists of a set of plug-ins integrated within the Eclipse IDE. In the framework of the CHESS project, this thesis addresses the lack of well integrated means concerning quality evaluation and proposes an integrated framework to evaluate the dependability of high-integrity embedded systems. After a survey of various failure behavior analysis techniques, a specific technique, called Failure Propagation and Transformation Calculus (FPTC), is selected and a plug-in, called CHESS-FPTC, is developed within the CHESS tool-set. FPTC technique allows users to calculate the failure behavior of the system from the failure behavior of its building components. Therefore, to fully support FPTC, CHESS-FPTC plug-in allows users to model the failure behavior of the building components, perform the analysis automatically and get the analysis results back into their initial models. A case study about AAL2 Signaling Protocol is presented to illustrate and evaluate the CHESS-FPTC framework.


Individual equity securities are prone to large and abrupt stock price drops. In this article, the authors provide a framework for measuring, forecasting, and avoiding such stock price crashes. First, the authors identify the events that most frequently cause stock prices to crash, and then they construct a parsimonious model for forecasting stock price crashes. Finally, they examine how positioning a portfolio to reduce exposure to stocks with high crash risk can improve investment performance. This article provides a framework that should help investors construct equity portfolios with fewer stock price crashes, higher returns, and lower volatility.


CONTEXT
The link between adolescent fiber consumption, inflammation, and body fat distribution has not been investigated.

OBJECTIVE
This study investigated associations of dietary fiber intake with inflammatory-related biomarkers and robust measures of total and central adiposity in a sample of 559 adolescents aged 14-18 yr (49% female, 45% Black).

METHODS
Fasting blood samples were measured for leptin, adiponectin, resistin, C-reactive protein, and fibrinogen. Diet was assessed with four to seven 24-h recalls, and physical activity was determined by accelerometry. Fat-free soft tissue mass and fat mass were measured by dual-energy x-ray absorptiometry. Visceral adipose tissue was assessed using magnetic resonance imaging.

RESULTS
Multiple linear regression, adjusting for age, race, Tanner stage, fat-free soft tissue mass, energy intake, and physical activity, revealed that dietary fiber intake was inversely associated with fat mass and serum leptin in males (all P < 0.03) but not in females. In both genders, dietary fiber intake was negatively associated with visceral adipose tissue, plasma C-reactive protein, and plasma fibrinogen and positively associated with plasma adiponectin (all P < 0.05). No relations were found between dietary fiber intake and plasma resistin in either males or females.

CONCLUSION
Our adolescent data suggest that greater consumption of dietary fiber is associated with lower visceral adiposity and multiple biomarkers implicated in inflammation.


Abstract. The utilization of dry steam as a low energy preprocessing step in the pelletization of switchgrass was evaluated in this work. Ground switchgrass was moisture-conditioned at 16% and 18% wet basis (w.b.) and then subjected to 100°C and 120°C steam treatment cycles in an autoclave before being formed into pellets. Similarly, pellets were formed from switchgrass moisture-conditioned at 16% and 18% without steam treatment (control). Determined metrics included particle density, particle size distribution, pellet density, diametral and axial strengths, and durability using both tumbling box and friabilator. Pellet density values were similar to particle density for all treatments suggesting pelleting produced highly compressed biomass with little voids remaining. Neither particle density nor pellet density significantly changed (p>0.05) due to steam conditioning. Although not significant (p>0.05), an increase in pellet diametral strength was observed for the 120°C dry steam conditioning compared to the non-steam conditioned and 100°C dry steam conditioning pellets. Axial strength of single pellets for control and dry steam conditioned materials were not significantly different (p>0.05). Pellet durability analysis resulted in an average friability of 93.8% for control and all treatments. The more aggressive box durability test indicates that dry steam conditioned pellets had a 7% to 10% lower durability compared to pellets formed using unconditioned switchgrass. Overall, the dry steam conditioning did not result in improved pellet quality for the tested moisture contents compared to the control. Future work is required to test the dry steam conditioning at other moisture and/or particle size levels.


ABSTRACT Trichomonas vaginalis is an important pathogen in both men and women. Culture is considered the diagnostic gold standard, although studies have shown that PCR is more sensitive than either culture or wet mount for the diagnosis of T. vaginalis infections. We sought to identify a simple method for stabilizing T. vaginalis DNA in urine samples that could be easily applied to molecular testing. The stability of T. vaginalis DNA in 40 urine samples was assessed by storage for various times at either 4°C or room temperature with or without the Becton Dickinson urine preservative transport (UPT) kit. Overall, there was better stability of T. vaginalis DNA when specimens were stored at 4°C than when they were stored at 20 to 22°C and when the UPT system was used. T. vaginalis DNA was stable in specimens stored without using the UPT at 4°C for about 3 days and at room temperature for only 1 day. For specimens placed in the UPT within 24 h (times of 1, 6, and 24 h) of collection, the DNA was stable for up to 30 days when stored at 4°C. For specimens stored at room temperature, the urine should be added to the UPT ideally within 1 hour of collection, and in this case the DNA remained stable for up to 30 days. When storing specimens at room temperature, a delay of 24 h prior to adding to UPT led to an unacceptably high loss of assay sensitivity.


The protein product of the gene responsible for ocular albinism type 1, named OA1, is a pigment-cell-specific membrane glycoprotein, displaying features of G-protein-coupled receptors, yet exclusively localized to late endosomes, lysosomes and melanosomes. To dissect the signals responsible for the intracellular localization of OA1, we generated chimeric proteins consisting of the cytosolic domains of OA1 fused to the lumenal and transmembrane domains of LAMP1; in addition, we generated missense and deletion mutants of full-length OA1. Using this approach, we identified two separate sorting signals that are both necessary and sufficient for intracellular retention, as well as lysosomal and melanosomal localization, in melanocytic and non-melanocytic cells. These sorting signals are an unconventional dileucine motif within the third cytosolic loop and a novel motif, characterized by a tryptophan-glutamic acid doublet, within the C-terminal tail. Both motifs must be mutated to promote the plasma membrane localization of OA1, suggesting that they can independently drive its intracellular targeting. In addition, both motifs act similarly as lysosomal sorting signals in non-melanocytic cells, but appear to carry different specificities in melanocytic cells. Our findings indicate that OA1 contains multiple unconventional signals responsible for its lysosomal and melanosomal localization, and reveal a remarkable and unforeseen complexity in the regulation of polytopic protein sorting to specialized secretory organelles.


The 2002 Romanow Commission on the Future of Health Care recommended improvements in education and practice in end-of-life care for a growing and aging Canadian population. The aim of this study was to design, develop, and evaluate a continuing professional development program in end-of-life care for accreditation by the Ontario College of Family Physicians. The challenge was to provide a robust, interactive program easily accessible to busy family doctors distributed over a large geographic area. A comprehensive and collaborative knowledge building model, blending asynchronous Knowledge Forum® technology and synchronous interactive videoconferencing was created, to enable individual knowledge improvement and community advancement of ideas in clinical practice. The focus of this design research was a novel method of online, embedded and concurrent self-assessment. Results indicated gains in understanding and program satisfaction associated with knowledge building participation.


ABSTRACT Legionella pneumophila uses the Icm/Dot type 4B secretion system (T4BSS) to deliver translocated protein substrates to the host cell, promoting replication vacuole formation. The conformational state of the translocated substrates within the bacterial cell is unknown, so we sought to determine if folded substrates could be translocated via this system. Fusions of L. pneumophila Icm/Dot-translocated substrates (IDTS) to dihydrofolate reductase (DHFR) or ubiquitin (Ub), small proteins known to fold rapidly, resulted in proteins with low translocation efficiencies. The folded moieties did not cause increased aggregation of the IDTS and did not impede interaction with the adaptor protein complex IcmS/IcmW, which is thought to form a soluble complex that promotes translocation. The translocation defect was alleviated with a Ub moiety harboring mutations known to destabilize its structure, indicating that unfolded proteins are preferred substrates. Real-time analysis of translocation, following movement during the first 30 min after bacterial contact with host cells, revealed that the folded moiety caused a kinetic defect in IDTS translocation. Expression of an IDTS fused to a folded moiety interfered with the translocation of other IDTS, consistent with it causing a blockage of the translocation channel. Furthermore, the folded protein fusions also interfered with intracellular growth, consistent with inefficient or impaired translocation of proteins critical for L. pneumophila intracellular growth. These studies indicate that substrates of the Icm/Dot T4SS are translocated to the host cytosol in an unfolded conformation and that folded proteins are stalled within the translocation channel, impairing the function of the secretion system.


The database community has made rapid strides in capturing, representing, and querying uncertain data. Probabilistic databases capture the inherent uncertainty in derived tuples as probability estimates. Data acquisition and stream systems can produce succinct summaries of very large and time-varying datasets. This tutorial addresses the natural next step in harnessing uncertain data: How can we efficiently and quantifiably determine what, how, and how much to learn in order to make good decisions based on the imprecise information available. The material in this tutorial is drawn from a range of fields including database systems, control and information theory, operations research, convex optimization, and statistical learning. The focus of the tutorial is on the natural constraints that are imposed in a database context and the demands of imprecise information from an optimization point of view. We look both into the past as well as into the future; to discuss general tools and techniques that can serve as a guide to database researchers and practitioners, and to enumerate the challenges that lie ahead.