Purpose: In plan optimization of intensity‐modulated radiation therapy(IMRT), all voxels inside the same structure are treated equally. In realty, the spatial location of hot/cold spots does have some clinical. One example is that hot spots, if cannot be removed, are more preferred to be located at the center, rather than the edge, of the tumor. Our goal is to develop a method that while preserving the plan quality represented by the DVH curves, reallocates hot and cold spots to more clinically preferred locations, by incorporating voxel's spatial information into the optimizationmodel. Methods and Materials: In traditional optimizationmodels, usually a convex objective function penalizes the deviation of the dose received by each voxel from its prescribed (if it is part of the target) or threshold dose (if it is part of a critical structure). In our model, instead of assuming an equal weight for all voxels inside a structure, we associate weights as a function of their physical position in the structure. By this modification, our model incorporates voxel‐based penalty weights for overdosing (penalizing the presence of hot spots) and underdosing (penalizing the presence of cold spots) depending of the location in the structure. The resulting convex optimization problem is solved by implementing a gradient algorithm with Armijo search. Results: We tested our model in four prostate cancer cases and we compare the characteristics of resulting hot/cold spots to those resulting from a correspondingly model without incorporating spatial information. It is observed that without sacrificing the plan quality represented by the DVH curves, our model relocates the hot/cold spots to more desired positions. Conclusions: We have proposed a new optimizationmodel that, by incorporating voxel's spatial location information, generates similar DVH curves to those from traditional model, while capable of redistributing hot/cold spots to more desirable locations.


This paper proposes a new framework to analyze the behavior of "public advocates", defined as professionals who seek to influence public policy on behalf of the public interest. Using the framework, it describes systemic pressures that lead public advocates to overuse adversarial, coercive tactics. The framework classifies each action of a public advocate into four broad categories based on choices about "strategy" (how to use available resources to cause change) and "stance" (the mental map of the person or institution that s/he seeks to influence). Alternative strategies can be arrayed on a continuum from "push" to "pull", and alternative stances from "friend" to "foe". Using a matrix or grid, advocacy to influence a particular target can be characterized as push-foe, push-friend, pull-foe, or pull-friend. Based on extensive personal experience, the author suggests that the choice of stance is subject to a systemic negative bias: in a sustained dispute, most competing advocates will come to see the "other" as foes. A foe stance distorts judgment about strategy so that push strategies appear to be the only realistic option. This explains the prevalence of what the author calls the "Advocacy Trap", where advocates continue to treat others as enemies (foe stance) to be attacked and discredited (push strategy) despite repeated failure. To the extent that successful public advocacy requires a judicious mix of push and pull strategies, public advocates need to maintain a stance of respect in the face of hostility. The author concludes by calling for a new conversation among educators, scholars, philanthropists, foundations, citizen activists and journalists on how to educate, recognize, and support public advocates who embody this approach.


The aim of this work is to analyze some equilibrium consequences of the behavior of heterogeneous ambiguity averse agents in inter-temporal general equilibrium models. As the focus is on the influence of ambiguity aversion, the choice of the models treated here was based on their previous use to attain similar results, allowing their use as a parameter. Because of that, it is considered here a general equilibrium model which fits in frameworks like in Araujo and Sandroni (1999), Sandroni (2000), Blume and Easley (2006) and Condie (2008). Two different approaches have been used: in the first (Chapter 2) we strive to find out what condition of beliefs is necessary to achieve equilibrium, and in the second (Chapter 3) we want to know what conditions are related to survival. There is also a chapter of preliminaries where the framework is discussed and some auxiliary results are presented. The first results are within the framework of Araujo and Sandroni (1999) where there is a complete market of contingent claims and bankruptcy is permitted, though incurring a penalty. Agents have the smooth ambiguity preferences presented by Klibanoff et al. (2005, 2009). The main result follows those others presented in the literature, but provides quite a different interpretation. It proves that a necessary condition for equilibrium existence is the convergence of ambiguity perception reduction. Other results are placed within the context of Blume and Easley (2006), where behavior is analyzed from the point of view of Pareto Optimal allocations. In this case, agents' behavior is determined by variational preferences (axiomatized by Macheroni et al. (2006a,b)). These preferences are more general than the expected utility (used by Sandroni (2000) and Blume and Easley (2006)) and maxmin utility (used by Condie


Following significant social and legal challenges to Australia's colonial policy of 'offshoring' immigration detention, the system has become more mobile and diffuse, expanding through a range of new, ad-hoc, and established detention sites both 'on' and 'offshore'. Refugees, asylum seekers and other non-citizens are frequently transferred and dispersed between these sites, which form 'spaces of disappearance'. In this article, we draw upon concepts of racial surveillance capitalism and data justice to analyse a work by the Manus Recording Project Collective, titled where are you today, that sought to expose and counter the colonial border's disappearing effects. The work involved the creation and distribution of audio-recordings from inside detention sites to subscribers. Recordings were distributed via text messages that also plotted individual subscribers in spatiotemporal relation to the detained artists that created them. The Collective thereby appropriated the tools of surveillance capitalism – such as GPS tracking and timestamping – to create dynamic digital cartographies of the mobile-carceral border. Through studying this work, we aim to deepen understandings of colonial bordering practices and highlight possibilities for disrupting the social divisions and exclusions that they reproduce.


Objective: This study aimed to explore the development of working conditions within and between occupations in the Swedish labor market from 1997 to 2015 and whether any polarization in working conditions concurrently occurred between occupations. Methods: Cross-sectional data from ten waves of the Swedish Work Environment Surveys (1997–2015) were used and an aggregated occupational-level dataset was created using the Swedish Standard Classification of Occupations. To capture the patterns of change in working conditions over time (ie, growth), growth curve modeling was used to identify the starting points for 89 occupations (intercepts) as well as both the shape (functional form) and rate of growth (slope) over time. Results: The Swedish labor market was stable overall, with some small, mainly positive, changes in job demands and resources. Different occupations developed in divergent directions, but there was no evidence of polarization. Conclusions: The findings indicate that macro-level stability can hide highly heterogeneous patterns of change among different occupational groups. This type of analysis, taking context into account, could be valuable for decision makers intending to improve the work environment.


The fatty acid and glucose incorporation into glycerides and glycerol release from adipose tissue were determined in a middle‐aged population of 109 men and 41 women. 43 men and 19 women were rrormolipidaemic. The same analysis was also carried out in 13 male and 9 female normolipidaemic students. Needle biopsy specimens of adipose tissue were incubated in vitro in an albumin medium containing 3H‐fatty acids and 14C‐glucose. After two hours of incubation values for fatty acid and glucose incorporation were calculated from the incorporation of 3H‐activity into the fatty acids and 14C‐activity into the glycerol moiety of extracted glycerides. The mean values for fatty acid incorporation were lower in all types of hypertriglyceridaemic subjects (II B, III, IV and V) than in the normolipidaemic control subjects. In the male hypertriglyceridaemic population 36 % had values for fatty acid incorporation below the 5th percentile of the normolipidaemic group and 14 % had values below the lowest normal value. The rate of fatty acid incorporation was negatively correlated with the serum triglyceride concentration. This correlation remained unchanged when partial correlation was performed when the influence of body weight was eliminated. Fatty acid and glucose incorporation correlated positively. Incorporation of glucose behaved in the same way as described above for incorporation of fatty acids. Glycerol and fatty acid release was the same in the normo‐ and hypertriglyceridaemic groups. It is likely that the removal of plasma triglycerides from blood requires hydrolysis of triglycerides to fatty acids and the subsequent removal of the fatty acids. The hypothesis has been formulated that when the former process is normal, a defect of fatty acid removal (a low rate of fatty acid incorporation into glycerides) may be responsible for an impaired removal of plasma triglyceride‐fatty acids. A low rate of fatty acid incorporation may contribute to the development of hypertrigiyceridaemia, according to this hypothesis.


Technological developments have left indelible impacts on the economy all along the line. Every novel invention realized changes production processes rapidly, which concomitantly transforms social life. One of the most apparent examples of this is the First Industrial Revolution emerged in the 18 th Century. Subsequent to this development which was considered as the beginning of production in the factory environment, the second industrial revolution based on automation (First half of 20 th Century) and the third Industrial Revolution based on electronics (last quarter of the 20 th century) were realized. Finally, the Fourth Industrial Revolution (Industry 4.0) process was initiated by Germany in 2011. In line with this process in which cyber-physical systems and robotic technologies are expected to prevail, Super-Smart Society (Society 5.0) model was developed by Japan in 2017. Both Industry 4.0 and Society 5.0 implementations are expected to have a significant impact on economic and social life and to change both labor and Welfare State practices fundamentally. It is also possible that these aforementioned developments may have an impact on social security system of the government. Likewise, the emergence of extensive unemployment condition due to robotic technologies and training for adaptation of available labor force to the new technologies may lead to redesign of the social security system. The aim of this study is to demonstrate the possible impacts of the Industry 4.0 and Society 5.0 processes on social security expenditures. The basic result obtained from the study; unemployment increase and training activities for the labor-force increases social security expenditures, but however digitalization process in Welfare State implementations may be expected to decrease social security expenditures in the long-run depending on efficiency and effectiveness increases in the government.


Pathology slide images capture tumor histomorphological details in high resolution. However, manual detection and characterization of tumor regions in pathology slides is labor intensive and subjective. Using a deep convolutional neural network (CNN), we developed an automated tumor region recognition system for lung cancer pathology slides. From the identified regions, we extracted 22 well-defined tumor shape features and found that 15 of them were significantly associated with patient survival outcome in lung adenocarcinoma patients from the National Lung Screening Trial. A tumor shape-based prognostic model was developed and validated in an independent patient cohort (n=389). The predicted high-risk group had significantly worse survival than the low-risk group (p value = 0.0029). Predicted risk group serves as an independent prognostic factor (high-risk vs. low-risk, hazard ratio = 2.25, 95% CI 1.34-3.77, p value = 0.0022) after adjusting for age, gender, smoking status, and stage. This study provides new insights into the relationship between tumor shape and patient prognosis.


Lysozme, a humoral defence protein, played an important bactericidal activity in Atlantic salmon and halibut. Turbidometric and bactericidal killing assays were used to determine the lysozyme level and serum killing activity respectively. A challenged experiment in native halibut ( Hippoglossus hippoglossus ) with different doses (10 3 ,10 5 , 10 9 ) of Aeromonas salmonidae (MT423) has been proved that there is no significant relationship between the lysozyme level and bactericidal killing activity (p>0.005). Lysozyme level in halibut serum was significantly higher than that of Atlantic salmon serum. Lysozyme activity of serum collected from fish during the summer was found to be significantly higher, ranging from 650 to 850 µg. Halibut serum showed varying level of killing activity (KI) during summer (0.266-0.873) and winter (0.255-1.344) whereas Atlantic salmon had very poor killing activity (0.414 -6.867). There was no correlation between the lysozyme activity of the serum and bactericidal activity in the serum of A. salmonicida infected halibut.


One of the conclusions from comparative empirical studies of the structural challenges towards making global production and consumption patterns compatible with environmental limits is that rich countries would need to 'degrow' (O'Neill 2015; Fritz and Koch 2016). To shed light on the potential role of the state in such a planned downscaling process the paper compares state roles in a capitalist economy (oriented at monetary growth or exchange value) and a postgrowth economy (oriented at physical parameters such as matter and energy throughput or use values). First, contributions to materialist state and regulation theories are applied to analyse the state's roles in a capitalist growth economy: above all as rule of law, welfare state, environmental state and in relation to state spatiality. To these roles correspond economic policies to intermediate corporate interests, social policies to de- and recommodify labour power and environmental policies to produce 'green growth'. Second, the paper argues that state roles would need to change to bring forth environmental sustainability and social equality in a postgrowth context. State economic, social and environmental policies would be oriented at the provision of 'sustainable welfare' (Koch and Mont 2016), specifically the provision of sufficient need satisfiers for all people now and in future (Gough 2015). It is generally argued that robust (welfare) states would be necessary to steer a mixed economy that functions within environmental limits and serve as primus inter pares in a governance network comprising above all global and local levels. Finally, the paper discusses state 'eco-social' policies such as wealth sharing, minimum and maximum incomes as well as carbon rationing that can facilitate the transformation from a growth to a postgrowth economy. Such policies potentially serve as 'real utopian' alternatives to capitalism (Wright 2010) and the traditional environmental state.


Puerperal hematoma is an uncommon complication of childbirth with a potential for serious morbidity and possible mortality. Prevention, using good surgical technique with attention to hemostasis in the repair of lacerations and episiotomies, should limit the occurrence of this complication. Puerperal hematomas, however, are not unavoidable. Thus, one must be alert to the possibility so that the hematoma can be diagnosed early and treated aggressively. This includes correcting hypovolemia and intervening with active surgical management if the hematoma is large or expanding.


Two groups of male, 9-week-old goats (5 goats/group) were vaccinated subcutaneously with formalized exotoxin of Corynebacterium pseudotuberculosis, with Freund's incomplete adjuvant. Each goat was given 2 vaccinations, 2 weeks apart. At each vaccination, each group 1 goat was given 0.5 ml of toxoid, and each group 2 goat was given 1 ml of toxoid. Twenty days after the 2nd vaccination, vaccinated goats and 5 nonvaccinated 12-week-old goats (controls) were inoculated intradermally (challenge exposed) with live C pseudotuberculosis, monitored for 13 weeks, and euthanatized. At necropsy, 5 of the 10 vaccinated goats did not have C pseudotuberculosis lesions, 3 had abscesses limited to the inoculation site and draining lymph node, and 2 had disseminated bacterial lesions. Of the 5 nonvaccinated controls, 4 had disseminated abscesses and 1 had a single abscess in an internal node. Serologically, 9 of the 10 vaccinated goats developed positive (greater than or equal to 1:8) antibody titers against the exotoxin within 1 week after inoculation; the 10th goat seroconverted 2 weeks after inoculation, whereas control goats required 3 weeks to develop a positive antibody response. Therefore, early during an infection with C pseudotuberculosis, antibodies against the exotoxin may protect a goat against spread of the organism. All goats were injected intradermally before challenge exposure, 10 days after challenge exposure, and at 4, 8, and 12 weeks after challenge exposure with a skin-test reagent composed of fragmented bacterial cells.(ABSTRACT TRUNCATED AT 250 WORDS)


Both exercise training (Ex) and superoxide dismutase (SOD) mimetic tempol have antihypertensive and renal protective effects in rodent models of several hypertensions. We recently reported that Ex increases nitric oxide (NO) production and the expression levels of endothelial and neuronal NO synthase (eNOS and nNOS) in the kidney and aorta of the spontaneously hypertensive rats (SHR) and normotensive Wistar–Kyoto rats (WKY). We also found that endogenous hydrogen peroxide (H2O2) upregulates the expression levels of eNOS and nNOS in SHR. To elucidate the mechanism of the Ex-upregulated NO system in the kidney, we examined the additive effect of Ex and tempol on the renal NO system in SHR and WKY. Our data showed that, in SHR, both Ex and tempol increase the levels of H2O2 and nitrate/nitrite (NOx) in plasma and urine. We also observed an increased renal NOS activity and upregulated expression levels of eNOS and nNOS with decreased NADPH oxidase activity. The effects of the combination of Ex and tempol on these variables were cumulate in SHR. On the other hand, we found that Ex increases these variables with increased renal NADPH oxidase activity, but tempol did not change these variables or affect the Ex-induced upregulation in the activity and expression of NOS in WKY. The SOD activity in the kidney and aorta was activated by tempol only in SHR, but not in WKY; whereas Ex increased SOD activity only in the aorta in both SHR and WKY. These results indicate that Ex-induced endogenous H2O2 produced in the blood vessel and other organs outside of the kidney may be carried to the kidney by blood flow and stimulates the NO system in the kidney.


The total food industry system in the United States is visualized as a nationwide network linking major market area components (products, consumption and structure) to major systems components (e.g. information systems, financial structure, transport and legal-regulatory) for the major market areas of the country. Emphasis is placed on identification and measurement of the linkages and relationships between and among this myriad of system components. A cooperative national effort is urged to model the system for measurement and evaluation of current and future food systems.


Background: Obesity and poor respiratory function are associated with morbidity and mortality. Obesity affects lung function, however the impact of all degrees of obesity on lung function need to be explored in different populations and genders. Aims and Objectives: The authors investigated the relation of BMI, waist circumference, physical activity with lung function in Hail City, Saudi Arabia. Materials and Methods: This analysis included 359 females aged 18–44 years with no known preexisting serious illness and who had complete anthropometric (height, weight and waist circumference) and forced vital capacity (FVC) using simple spirometry and chest measurements. Physical activity was measured using "International Physical Activity Questionnaire" (IPAQ). Results: Both FVC and predicted FVC along with chest expansion measurements were linearly and inversely related across the entire range of body mass index (BMI) and waist circumference (WC) and positively associated with physical activity in study subjects even after adjusting for age confirming our hypothesis. However, BMI and physical activity explained the greatest proportion of variance for both FVC and chest expansion in regression analysis as compared to WC. Conclusion: In the general adult female population, obesity may play a role in the impairment of lung function even from BMI ≥ 35 kg/m2 while even moderate physical activity can positively affect lung function.


Based on the Lyapunov stability theorem, a model reference adaptive sliding mode control scheme is proposed in this paper for a class of multi-input multi-output (MIMO) dynamic systems with mismatched model uncertainties and external disturbances in order to solve robust tracking problems. In this method adaptive mechanisms are employed both in sliding surface function and control effort so that once the dynamics of controlled system enter the designated sliding surface, the trajectories of tracking errors can achieve asymptotic stability even if the mismatched perturbations exist. In addition, with adaptive mechanisms embedded in the proposed control scheme, the controller is able to adapt the unknown upper bound of perturbations without requiring the information of upper bound of perturbations. A numerical example is given for demonstrating the feasibility of the proposed control scheme.


In the 1960s Anton Ehrenzweig devised an experimental course for school art teachers based on his deep knowledge of British psychoanalytic theory, especially Melanie Klein's ideas of projection and introjection. Ehrenzweig's early advocacy for the idea of an artist teacher, which formed a key element of his Art Teachers Certificate course at Goldsmiths, could be seen as ahead of its time, anticipating some of the ideas and practices of the past couple of decades. However, his claim that good teachers use their pupils as a medium for the teacher's own creativity raises ethical questions that still resonate today. In this article, I will draw out some comparisons between Ehrenzweig's theories of creativity and art education, and recent writing on the artist teacher. I will consider ways in which Ehrenzweig's development of Kleinian psychoanalytic theory can both complement and challenge current thinking about the merging and differentiation of artist, teacher and student identities.


Art-based learning is a way of engaging the intellectual, affective, visual and kinaesthetic domains modelling creative, lateral thinking and personal meaning-making through metaphor as well as coaching dialogue. It is a form of experiential learning involving learning cycles to entice deep reflection in and on practice and deep, transformative learning. Art-based learning is essential to the studies of Expression and Communication and of Transpersonal Art Therapy (TAT). This journal-type essay explores what happened during an arts-based activity as part of the author's study in TAT practice. The activity concerned finger-painting 'the journey of self-realisation' and the resulting imagery was used to coach dialogue. Describing the process through a series of steps, the author discusses the experiences and insights that emerged during and after the process. Though subjective and not necessarily applicable to all situations, this essay may encourage tertiary educators of studies in Education and Health to ...


This article focuses on the use of critical discourse analysis in ethnographic research on homosexual and transsexual identity in eastern Slovakian Roma settlements. Critical Discourse Analysis offers a methodological and analytical system for handling the identifi cation process of these actors. Using some premises of Norman Fairclough's critical discourse analysis, the author attempts to demonstrate how homosexual and transsexual individuals (labelled using native categories such as homosexaulis, gayos, buzerantos, kerado, or tato) are identified, and how this process of identifi cation is linked to existing social practices. In the analysis the author focuses on analytical issues, including the problem of identifying buzerantos and the semiotic aspects of identification methods that can be observed in the context of conjunctural events of social practice. Other issues the author deals with include how this identification process relates to genre, style and discourse, how subjectivity is involved in discourse, and in what ways members' resources are changing the limits of discourse. The fi nal point analysed is the practice of homosexuality and transsexuality as an alternative discourse type, which challenges the strategies of stigmatisation and changes the classifi cation frames governing what is appropriate or inappropriate.


A laser based needle-free liquid drug injection device has been developed. A laser beam is focused inside the liquid contained in the rubber chamber of micro scale. The focused laser beam causes explosive bubble growth, and the sudden volume increase in a sealed chamber drives a microjet of liquid drug through the micronozzle. The exit diameter of a nozzle is 125 μm and the injected microjet reaches an average velocity of 264 m/s. This device adds the time-varying feature of microjet to the current state of liquid injection for drug delivery.


Galactose in serum and galactose-1-phosphate in erythrocytes were measured in six transferase deficient children to determine if these metabolites could be used in detecting transferase deficient galactosemia. In all six children the galactose levels were normal and the galactose-1-phosphate elevated. The galactose level depends on diet and the rate of metabolism to galactose-1-phosphate and, therefore, should not be used to predict transferase deficient galactosemia. The galactose-1-phosphate level was elevated in all the transferase deficient children because once formed it cannot be metabolized. Measurement of galactose-1-phosphate is difficult and is usually requested to determine whether or not the child is following the galactose restricted diet. In transferase deficient galactosemia, the enzyme hexose-1-phosphate uridylyltransferase is absent. The diagnosis should be determined by measurement of the activity of the enzyme hexose-1-phosphate uridylyltransferase in erythrocytes. In galactokinase deficient galactosemia, the enzyme galactokinase is absent. Galactose levels are elevated but the amount present depends on diet and how soon the blood was collected after the ingestion of galactose containing foods. The diagnosis of galactokinase deficient galactosemia is based on the measurement of the enzyme galactokinase in erythrocytes.


The simulation studies were carried out on the oriented silicon steel produced by thin slab casting and rolling (TSCR) and twin-roll strip casting in the laboratory. The precipitation of inhibiter, formation of microstructure and texture were investigated before cold rolling. The inhomogeneous microstructure and texture gradient were observed in the 7-pass hot-rolled strip(2mm)for TSCR process, and texture gradient was not changed after normalizing, and the twin-roll strip casting directly supplied a strip with approx 2mm of thickness being same as that of hot-rolled strip by TSCR. The microstructure of twin-rolling casting strip was almost composed of all equiaxed grains which similar to the normalizing microstructure in TSCR process, but the random texture was obtained by twin-rolling strip casting. The dispersed and clustered precipitates were presented in hot-rolled strip when the ingots were soaked at 1200°C and 1150°C respectively for the TSCR process. And disperse and acicular precipitates were observed by TEM for air-cooling cast strips for process twin-rolling casting.


Bacterial trimethylamine dehydrogenase contains a novel type of covalently bound flavin mononucleotide and a tetrameric iron-sulphur centre. The dehydrogenase takes up 1.5mol of dithionite/mol of enzyme and is thereby converted into the flavin quinol-reduced (4Fe-4S) form, with the expected bleaching of the visible absorption band of the flavin and the emergence of signals of typical reduced ferredoxin in the electronparamagnetic-resonance spectrum. On reduction with a slight excess of substrate, however, unusual absorption and electron-paramagnetic-resonance spectra appear quite rapidly. The latter is attributed to extensive interaction between the reduced (4Fe-4S) centre and the flavin semiquinone. The species of enzyme arising during the catalytic cycle were studied by a combination of rapid-freeze e.p.r. and stopped-flow spectophotometry. The initial reduction of the flavin to the quinol form is far too rapid to be rate-limiting in catalysis, as is the reoxidation of the substrate-reduced enzyme by phenazine methosulphate. Formation of the spin-spin-interacting species from the dihydroflavin is considerably slower, however, and it may be the rate-limiting step in the catalytic cycle, since its rate of formation agrees reasonably well with the catalytic-centre activity determined in steady-state kinetic assays. In addition to the interacting form, a second form of the enzyme was noted during reduction by trimethylamine, differing in absorption spectrum, the structure of which remains to be determined.


&NA; Familial hypercholesterolemia (FH) is caused by mutations in the low density lipoprotein receptor (LDLR) gene. To study the impact of mutations affecting the hydrophobic transmembrane domain of the LDLR, each of the 22 amino acids of the transmembrane domain was individually mutated to arginine. The more centrally in the transmembrane domain an arginine was located, the lower amounts of the 120 kDa precursor LDLR in the endoplasmic reticulum were observed. This led to lower amounts of the 160 kDa mature LDLR on the cell surface. For the mutants V797R‐LDLR, L798R‐LDLR and L799R‐LDLR a proportion of full‐length receptors including the transmembrane and cytoplasmic domains, was secreted into the endoplasmic reticulum lumen to appear in the culture medium. When the transmembrane domain of the epidermal growth factor receptor (EGFR) was replaced by that of the mutant L799R‐LDLR, similar effects were observed for the EGFR as for L799R‐LDLR. Introducing arginines in the transmembrane domain of the LDLR also affected metalloproteinase cleavage of the ectodomain and &ggr;‐secretase cleavage within the transmembrane domain. The most likely explanation for the low amounts of the 120 kDa precursor is that a basic residue in the hydrophobic transmembrane domain prevents the mutant LDLR from being inserted in the endoplasmic reticulum membrane from the Sec61 translocon complex. As a consequence, quality control systems could be activated. However, our data indicate that proteasomal degradation, lysosomal degradation, autophagy or ectodomain cleavage were not the underlying mechanism for degradation of these mutant LDLRs.


Although enthusiasm for the "killer-application" in the mobile sector has decreased, location based services still seem to be valuable mobile services. Today's location based services are mostly forced to use the proprietary location information provided by mobile network operators. The approach that is discussed here depicts a way of locating a mobile client independently from certain network operators and in heterogeneous networks. The Location Trader system collects and provides location information for users and providers of location based services. The accumulated interaction of each user of the user community enables to generate reliable location information in the Location Trader database. This paper prepares the groundwork for modeling the core principles of unintended value co-production with the Location Trader System. We intend to focus our analysis on the Location Trader System resp. Services, as the phenomenon of value co-production is widespread because of low coordination costs for integration and transactions enabled by immateriality and potential automation of business and transaction processes. The focus of this paper is the simulation of the user integration based on the theoretical basis.


&NA; Elevated level of homocysteine (Hcy) is considered a risk factor for neurodegenerative diseases, but the mechanisms remain to be established. Because high Hcy is associated with an up‐regulation of the ALOX5 gene product, the 5Lipoxygenase (5LO), herein we investigated whether this activation is responsible for the Hcy effect on neurodegeneration or is a secondary event. To reach this goal, wild type mice and mice genetically deficient for 5LO were assessed after being exposed to a diet known to significantly increase brain levels of Hcy. Confirming compliance with the dietary regimen, we found that by the end of the study brain levels of Hcy were significantly increase in both groups. However, diet‐induced high Hcy resulted in a significant increase in A&bgr;, tau phosphorylation, neuroinflammation, synaptic pathology and memory impairment in control mice, but not in mice lacking ALOX5. Taken together our findings demonstrate that the up‐regulation of the ALOX5 gene pathway is responsible for the development of the biochemical and behavioral sequelae of high Hcy brain levels in the context of a neurodegenerative phenotype. They provide critical support that this gene and its expressed protein are viable therapeutic targets to prevent the onset, or delay neurodegenerative events in subjects exposed to this risk factor.


The quest for safety improvement with weight reduction of vehicles and consequently lower fuel consumption, led the automotive industry to begin research into the third generation of advanced high strength steels. These steels present complex microstructures, composed of martensite, bainite and stable retained austenite. Two of the main treatments for obtaining these microstructures are the low temperature austempering and Quenching and Partitioning (Q&P). The objective of this work is to evaluate the microhardness and adhesive wear performance of a high silicon steel alloyed with niobium submitted to the treatments mentioned above. The austempering treatment was conducted at 340 °C for 1 and 3 hours. Partitioning steps in Q&P were performed at 250 °C for 10, 30 and 60 minutes. Results shows that niobium addition promotes changes in the bainite morphology which improved the wear resistance.


ABSTRACT Application of glyphosate (N-[phosphonomethyl] glycine) to Bradyrhizobium sp. (Lupinus)-nodulated lupin plants caused modifications in the protein pattern of bacteroids. The most significant change was the presence of a 44-kDa polypeptide in bacteroids from plants treated with the higher doses of glyphosate employed (5 and 10 mM). The polypeptide has been characterized by the amino acid sequencing of its N terminus and the isolation and nucleic acid sequencing of its encoding gene. It is putatively encoded by a single gene, and the protein has been identified as a putative porin. Protein modeling revealed the existence of several domains sharing similarity to different porins, such as a transmembrane beta-barrel. The protein has been designated BLpp, for Bradyrhizobium sp. (Lupinus) putative porin, and would be the first porin described in Bradyrhizobium sp. (Lupinus). In addition, a putative conserved domain of porins has been identified which consists of 87 amino acids, located in the BLpp sequence 30 amino acids downstream of the N-terminal region. In bacteroids, mRNA of the BLpp gene shows a basal constitutive expression that increases under glyphosate treatment, and the expression of the gene is seemingly regulated at the transcriptional level. By contrast, in free-living bacteria glyphosate treatment leads to an inhibition of BLpp mRNA accumulation, indicating a different effect of glyphosate on BLpp gene expression in bacteroids and free-living bacteria. The possible role of BLpp in a metabolite interchange between Bradyrhizobium and lupin is discussed.


The recent Segment Anything Model (SAM) represents a big leap in scaling up segmentation models, allowing for powerful zero-shot capabilities and flexible prompting. Despite being trained with 1.1 billion masks, SAM's mask prediction quality falls short in many cases, particularly when dealing with objects that have intricate structures. We propose HQ-SAM, equipping SAM with the ability to accurately segment any object, while maintaining SAM's original promptable design, efficiency, and zero-shot generalizability. Our careful design reuses and preserves the pre-trained model weights of SAM, while only introducing minimal additional parameters and computation. We design a learnable High-Quality Output Token, which is injected into SAM's mask decoder and is responsible for predicting the high-quality mask. Instead of only applying it on mask-decoder features, we first fuse them with early and final ViT features for improved mask details. To train our introduced learnable parameters, we compose a dataset of 44K fine-grained masks from several sources. HQ-SAM is only trained on the introduced detaset of 44k masks, which takes only 4 hours on 8 GPUs. We show the efficacy of HQ-SAM in a suite of 9 diverse segmentation datasets across different downstream tasks, where 7 out of them are evaluated in a zero-shot transfer protocol. Our code and models will be released at https://github.com/SysCV/SAM-HQ.


Human language constantly evolves due to the changing world and the need for easier forms of expression and communication. Our knowledge of language evolution is however still fragmentary despite significant interest of both researchers as well as wider public in the evolution of language. In this paper, we present an interactive framework that permits users study the evolution of words and concepts. The system we propose offers a rich online interface allowing arbitrary queries and complex analytics over large scale historical textual data, letting users investigate changes in meaning, context and word relationships across time.


Ge1-xMnx (x=0.05, 0.07, 0.11, 0.15, 0.19, 0.23, 0.26, 0.29) thin films were prepared by magnetron sputtering. All the films had a Ge cubic structure, and no indication of a secondary phase was found in any sample using X-ray diffraction (XRD). The crystal lattice constant increases with the Mn concentration, in accordance with Vegard's law. No films show clear magnetic domain structure under a magnetic force microscope (MFM). Atom force microscope (AFM) measurements show that all films have a uniform particle size distribution, and a columnar growth pattern. X-ray photoelectron spectroscopy (XPS) measurements indicate that the Mn atoms are not singlely in the bivalent. Electrical transport properties show that the resistance of the films increases with increasing Mn concentration, suggesting that the Mn ions are in deep-level acceptor states, while resistance decreases with increasing temperature, which is a typical semiconductor property.


The cell-surface adhesion molecule α6β4-integrin is a receptor for laminins and a component of hemidesmosomes. β4-Integrin expression is restricted to proliferating basal keratinocytes in the epidermis and is suppressed when differentiation commences. Altered β4-integrin expression levels correlate significantly with the aggressive behavior of cancers. In order to clarify the mechanisms that regulate transcription of the β4-integrin gene, we cloned its 5′-flanking region. This 5′-flanking region was found to have a high G + C content and not to contain either TATA or CAAT boxes. Nested delimitation and reporter analyses mapped a basal promoter to nucleotides −106 to +105, surrounding the most proximal transcription initiation site. Gel retardation and mutational analyses revealed that cooperation between AP1 and Ets, interacting with other factors, mediated the promoter activity. In addition to the promoter element, enhancer activity was found in the first intron (+1905/+3933) and in a sequence upstream of the promoter region (−414/−107). These findings should facilitate our understanding of the regulation of β4-integrin gene expression in processes such as cell growth and differentiation, apoptosis, and cancer development and metastasis.


Following the interaction of a neutrino with saline environment, the Cherenkov cone will be generated. The electromagnetic effect of the Cherenkov cone is perpendicular to the cone generator and it has the energy directly proportional to the neutrino energy. In the saline environment, neutrinos with very high energies (noise – 115 dBm) can be determined. Investigation of these neutrinos will lead to the construction of a Cherenkov detector. The construction of a Cherenkov detector involves the design and the construction of a very large number of detection elements and of cascade amplifiers. Another necessary condition is to know exactly the distribution of the dielectric parameters of the saline environment. In order to know the distribution of the dielectric parameters of the saline environment, it is necessary to make a map of their distribution. Under these conditions, the number of detection elements will be optimized and also the optimal position of the future Cherenkov detector will be determined. In this chapter, we will present the methodology of calculating the detection elements and a method to determine the dielectric parameters. Measurements of attenuation of the propagation of electromagnetic waves in this environment will be presented. We will detail how to optimize a Cherenkov detector.


EWSR1-FLI1, the chimeric oncogene specific for Ewing sarcoma (EwS), induces a cascade of signaling events leading to cell transformation. However, it remains elusive how genetically homogeneous EwS cells can drive heterogeneity of transcriptional programs. Here, we combined independent component analysis of single cell RNA-sequencing data from diverse cell types and model systems with time-resolved mapping of EWSR1-FLI1 binding sites and of open chromatin regions to characterize dynamic cellular processes associated with EWSR1-FLI1 activity. We thus defined an exquisitely specific and direct, super-enhancer-driven EWSR1-FLI1 program. In EwS tumors, cell proliferation was associated with a well-defined range of EWSR1-FLI1 activity; moreover, cells with a high EWSR1-FLI1 activity presented a strong oxidative phosphorylation metabolism. In contrast, a subpopulation of cells from below and above optimal EWSR1-FLI1 activity was characterized by increased hypoxia. Overall, our study reveals sources of intratumoral heterogeneity within Ewing tumors.


The influence of hydrogen peroxide on the dynamics of transition into uncultivable state (UCS) and on the reversion of V. cholerae and their subcultures, resistant to hydrogen peroxide, was studied. The transition of the initial cultures in river and distilled water into UCS took place earlier than that in resistant to hydrogen peroxide variants. The capacity for reversion to hydrogen peroxide resistant subcultures preserved, on the average, 2 - 3 times longer. An increase in the level of hydrogen peroxide in uncultivable populations was found to be 2.7 - 4.4 times. Subcultures, resistant to hydrogen peroxide, in the vegetative form had lower characteristics of peroxide concentrations than in uncultivable form (UCF), but somewhat higher than in initial variants. In revertants the concentration of hydrogen peroxide was lower in UCF, but somewhat higher than in vegetative cultures. The dynamics of the formation of UCF by cholera vibrios, with different degree of stability to the action of hydrogen peroxide, the accumulation of hydrogen peroxide in uncultivable populations, the deceleration of transition into uncultivable forms, an accumulation of hydrogen peroxide and an increase in the time of the reversion of clones, resistant to hydrogen peroxide, made it possible to suggest that the accumulation of hydrogen peroxide was possible to make an essential contribution to the formation of UCF of cholera vibrios in an experiment.


This Summer's World Cup in Russia will showcase an array of expensive footballing talent. Off the pitch, however, moves are also afoot to bring the sector under the auspices of European Union employment legislation. This Working Paper looks at regulation of the football 'industry' in the context of emerging supranational modes of sports governance and assesses the likely consequences of formalizing employment relations. At the moment, regulation of this highly commercialised industry, which has been rapidly transformed from voluntary, non-profit organisations to public limited companies, still mainly takes place at the national level. However, the EU has been extending its policy remit beyond the exclusively economic and has taken an increasing interest in football and other sports. Among its aspirations are for social partners take more of a role in regulating the sports sector. The Working Paper analyses the likely impact of this on employment relations in football with a focus on widely overlooked problems of transposition and implementation.


Nitrogen implanted titanium alloys with enhanced wear resistance have been synthesized under the conditions of energy and N++N2 +ion dose in the range of 30keV to 120keV and 3×1017ions/cm2 to 1×1018ions/cm2, respectively. Auger electron spectroscopy and X-ray diffraction show that supersaturated titanium solid solution with the gradient nitrogen concentration and titanium nitride compounds are formed in the surface modified regions of the materials. Enhanced wear resistance of the nitrogen implanted titanium alloy at energy of 120keV and ion dose of 1×1018ions/cm2 has been showed and explained on the basis of observed microstructure including the formation of micropits on the wear track in the present study.


Nanostructured Lanthanum hexaboride (LaB6) powders were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), high resolution transmission electron microscopy (HRTEM) and X-ray photoelectron spectra (XPS). The average size of LaB6 nanoparticles is about 35nm, which are well crystallized with ball or ellipsoid with inconspicuous corners and covered by a 3-5nm thick amorphous layer containing oxygen and carbon. The absorption of LaB6 nanoparticles in visible and near infrared spectrum (NIR) was measured and compared with micron scale particles. The surface plasmon responance (SPR) of nanoparticles was very efficient at NIR blocking, which almost covered the whole NIR region. The influence of nanoparticles concentration on spectrum absorption was comparatively evident. Meanwhile, micron particles almost haven't NIR blocking function.


The effect of central administration of angiotensin II (ANG II) on efferent renal sympathetic nerve activity (RSNA) was studied in conscious sheep. ANG II (1 nmol/h), infused for 30 min into the lateral cerebral ventricles in five sheep, did not alter mean arterial pressure (MAP) but reduced RSNA to 38 +/- 5% of control. Intracerebroventricular infusion of higher doses of ANG II (3 and 10 nmol/h), which increased MAP by 12 +/- 2 and 14 +/- 3 mmHg, respectively, reduced RSNA to 9 +/- 5 and 11 +/- 7% of control. MAP and RSNA gradually returned to control over a period of 2 h after the infusions. Intracerebroventricular losartan (1 mg/h for 1 h before, and then during, angiotensin infusion) blocked all the effects of angiotensin (3 nmol/h). Baroreflex relationships constructed from the beat-to-beat relationship of RSNA to diastolic pressure showed a significant leftward shift during intracerebroventricular ANG II compared with the control relationship. The beat-to-beat relationship between central venous pressure and RSNA was abolished during intracerebroventricular infusion of ANG II. These findings demonstrate that intracerebroventricular ANG II has a direct central inhibitory action on RSNA that is independent of both arterial and low-pressure baroreceptors. This effect of angiotensin is mediated by central angiotensin AT-1 receptors.


The interaction of imidazole with Co electrodes in an electrochemical system was studied by surface-enhanced Raman scattering (SERS) and electrochemical methods. The SER spectra of Co in an imidazole solution as a function of the applied potential were analyzed and the assignment of the Raman bands was made. It was found that there were three kinds of surface species on the Co surface in different potential regions and they were interchangeable depending on the potential. In a relatively negative potential region (-1.2 to -0.9 V), imidazole was adsorbed on the surface and its orientation might change from a vertical configuration via the N-end of the pyridine ring to a tilted configuration via the C2=N3 double bond. In a more positive potential region (−0.8 to −0.7 V), the SERS signal from the adsorbed imidazole weakened and finally disappeared, meanwhile the signal from the Co and imidazole complex strengthened gradually. At the open circuit potential (−0.6 V), we detected very strong bands from the Co oxides. By comparing the Tafel curves of the Co electrode in the solution without and with imidazole, we found that imidazole has a marked effect on the corrosion inhibition of the Co electrode. This result demonstrates that we may be able to reveal the complicated interaction of surface species with metal surface at the molecular level by combining the SERS and electrochemical methods.