Transit priority strategies have been implemented in many cities to improve levels of service for transit passengers and to encourage modal change. So far, researches on these methods encompass homogeneous traffic flow operating in disciplined lane movement, which is not the case in Dhaka city, where mixed traffic dominates and lacks lane discipline resulting traffic mishaps. Hence, this study endeavors to develop new-fangled bus priority schemes and evaluate its effectiveness in improving the road network performances by making quantitative comparison with existing priority methods to identify the most viable scheme for local traffic conditions. A wide range of traffic data of two peak periods comprising 7 hours of traffic flow in each of the 3 consecutive days, had been recorded and later extracted using image processing technique, from a section of 6-lane major artery road–Kazi Nazrul Islam Avenue to model the road network initially, which was later calibrated to simulate mixed traffic system. Furthermore, for each considered priority schemes, 20 different scenarios with varying traffic volume and bus to vehicle ratio have been simulated with VISSIM for 16,92,000 simulation seconds in total, to evaluate the effectiveness of priority methods for prevailing traffic conditions in terms of average traffic delay. The study proposed bus priority with intermittent bus lane, a new concept for dynamic bus lane, as to prioritize bus without compromising delay of other traffic, and hence, developed algorithm for simulating it in an urban road network for local traffic conditions, using Vehicle Actuated Programming within microsimulation software VISSIM. This priority method makes a lane intermittently dedicated to bus rather than exclusively dedicating the lane, making the prioritization of public transport adaptive with its demand in a signalized corridor. Furthermore, when the lane is not dedicated to bus, active bus priority was incorporated to improve the mobility of public transport upon the detection of bus prior to signal. Results show that bus signal priority minimizes average delay per vehicle by at least 40% or in some cases up to 120% more than what dedicated bus lane does in an urban road network having mixed traffic conditions, whereas the case is totally opposite while considering minimization of average delay per bus only due to the fact that even though signal priority is triggered upon the detection of bus prior to the signal, other vehicles get the advantage of green extension in case of active priority due to weak lane discipline that increases the degree of uncertainty of reaching the bus to stop line before red phase starts. This study also perceives proposed priority scheme to be effective in low volume of traffic with bus demand, referred as bus to vehicle ratio, up to 17.5% in the road network. Further rise in the bus demand makes dedicated bus lane preferable for the prevailing traffic condition. However, in case of bus demand below 12.5%, the priority method seems more potent in ameliorating the network performances up to 3500 veh/hr at most than other priority rules. This research may be used as a good reference for policy makers to choose the best bus priority alternatives by assessing their suitability for the prevailing traffic conditions of the road network under consideration.


Neutrophils are the most abundant nucleated cells in blood circulation and play important roles in the innate and adaptive immune responses. Neutrophil-specific antigens, only expressed on neutrophils, are glycoproteins originally identified in studies on neonatal neutropenia due to fetal-maternal incompatibility and autoimmune neutropenia of infancy. The most investigated neutrophil–specific antigens are the NA and NB antigens that their incompatibilities also cause transfusioninduced febrile reactions and acute lung injury, a potentially fatal reaction, and in bone marrow transplantation, causing graft rejection. NA antigens are members of the immunoglobulin superfamily and are low-affinity Fc-receptors FcγRIIIb (CD16b). Fc receptors connect the F(ab), the antigen-binding fragment of the antibody molecules, to neutrophils and lead them to recognize and phagocytize the targeted antigens. The NB (CD177) antigen belongs to the urokinase-type Plasminogen Activator Receptor Superfamily (uPAR, CD59, Ly6), but its specific functions have not been fully determined. It is known, however, that NB antigen binds proteinase-3 (PR3 to the neutrophil membrane), a serine protease. In clinical studies, it was also demonstrated that NB expression is highly elevated in Polycythemia Vera and is unexpectedly expressed in some cancer tissues. Neutrophil-specific antigens are examples of antigens that have important biological and clinical activities beyond antigenicity.


The micro-/nanoscopic structure of the hybrid organic-inorganic materials, based on polyether chains covalently linked to a silica framework through urea bridges, referred as ureasilicates or ureasils, and As2S3-ureasil composites with ion-implanted Ag nanoparticles is investigated. The formation of Ag nanoparticles is confirmed using optical transmission (surface plasmon resonance band of Ag nanoparticles) at ion-implantation doses of 2.5×1016 and 5.0×1016 ion/cm2 on the example of ureasil. It is established with scanning electron microscopy that incorporation of the As2S3 clusters into ureasil assists to ion-synthesis of Ag nanoparticles in polymer matrix, more effectively at higher doses of ion-implantation and for silver containing (As2S3)95Ag5-ureasil composite. (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)


This paper examined e-logistic practices and health care supply chain management in the context of Ugandan public referral hospitals. The prime objective was to examine the relationship between e-logistics operations and performance of health care supply chain management. A quantitative research approach was utilized to gather data from public referral hospitals respondents using structured survey questionnaires.  For data analysis, descriptive statistics and Partial Least Squares-Structural Equation Modelling were utilised, aided by SmartPLS 3. Findings showed a positive significant relationship between e-logistics operations and performance of health care supply chain management in the context of Ugandan public referral hospitals. This study implies that the key e-logistics operations in relation to the performance of health care supply chain management, are central management of drugs, the correct order picking of drugs given to the right patients for quality control, and presence of an electronic system to update stock daily. Additionally, the findings designated that, e-logistics operations are related to the performance of health care supply chain management in terms of ICTs tracking systems and data transparency. The practical implication to the health sector- stakeholders, is to consider ICT-tracking systems and data transparency for e-logistics operations and performance of health care supply chain management.


On the basis of the closed-time path formalism of non-equilibrium quantum field theory, we derive the real-time quantum dynamics of heavy quark systems. Even though our primary goal is the description of heavy quarkonia, our method allows a unified description of the propagation of single heavy quarks as well as their bound states. To make calculations tractable, we deploy leading-order perturbation theory and consider the non-relativistic limit. Various dynamical equations, such as the master equation for quantum Brownian motion and time-evolution equation for heavy quark and quarkonium forward correlators, are obtained from a single operator, the renormalized effective Hamiltonian. We are thus able to reproduce previous results of perturbative calculations of the drag force and the complex potential simultaneously. In addition, we present stochastic time-evolution equations for heavy quark and quarkonium wave function, which are equivalent to the dynamical equations.


Pheromone-stimulated male Heteropoda venatoria (L.) produce sounds during bouts of leg oscillations while coupled to the substratum by their tarsal adhesive hairs. No stridulatory organ is involved. Preventing palpal percussion and abdominal vibration does not eliminate primary sound production. Leg oscillation rates of 63, 83, and 125 Hz, roughly estimated from high-speed cinematographic samples of signalling, were within 1 SD of the mean frequencies of the lowest (Y = 88 Hz) or highest (Y = 146 Hz) frequency wave-trains, as indicated by oscillographic analysis of such sounds. These signals resemble and are analogous in origin to insect flight-sounds, the fundamental frequency being determined directly by the appendage oscillation rate. Hypotheses about the roles of vibration in these and other spiders, including araneids, are considered.


The objective of the study was to identify the vaginal douching habits and the factors that would have a connection with this practice in women from Eskisehir Province in Turkey. This descriptive and cross-sectional study was conducted from 1 May to 30 June, 2005. In present study, any sampling technique was not used. The subjects were women belonging to the 15 - 49 age groups who were admitted to No. 2 Family Planning Center and Sultandere Primary Health Care Center. A survey containing such questions about the socio-demographic and reproductive characteristics was conducted on these women via a face-to-face interview method. Among the statistical tests, chi-square test and logistic regression analysis were utilized. A total number of 503 women with an average age of 33.18 ± 7.50 were attended at the health center. Vaginal douching was performed in 47.7% women and the most common the method was cleansing (66.6%) and post-intercourse (71.8%). The information about these methods was obtained mostly from their mothers (31.6%). In accordance with the results obtained from the study, the vaginal douching practice is a widespread conventional attitude among women and should be given the necessary importance. It was concluded that it is necessary to provide health education for women who state that they get information concerning the practice mostly from their mothers and this wrong attitude change needs to be corrected. Since vaginal lavage is directly linked with low education levels and the state of unemployment, it is resolved that such measures should be taken to increase the socio-economic levels of women. It is also concluded that special importance should be attached to the health education of the primary health care profession concerning the vaginal lavage.

 Key words: Vaginal douching, practice, attitude, knowledge, Turkish women.


This work contributes to the field of human-system interaction modeling through an artificial intelligence approach. It focuses on the cooperative realization of a complex task. For this purpose, we propose a human-agent interaction model based on game theory to describe the decision making between the human operator and the assistant agent. The proposed model is based on searching Nash equilibria for a repeated two-player game in which each player has a choice between two actions. In particular, the assistant agent knows how to calculate the equilibrium that depends on information coming from the context (human operator and work environment). This approach allows us to consider a context aware human-machine system. Then, the assistant agent knows how to optimize its intervention with regard to the human operator assisted by this agent during a complex task. For the validation of our model, we highlight the efficiency of the assistant agent using this principle by considering a road traffic simulator using Netlogo. An analysis of the simulation results is provided to illustrate the effectiveness of our approach.


It is widely accepted that atherosclerosis and thrombus formation are closely associated. Recent progress in the development of molecular markers of blood coagulation and platelet enabled us to estimate even the slight activation of blood coagulation and platelet activation systems. We investigated a contract phase-activate coagulation and factor -inhibitor complex (factor XIa-alpha 1 antitrypsin) and expression of CD62P on platelet surface, a specific antigen on platelet, in patients with coronary arterial diseases. We compared these activation markers after stratifying patients according to the number of significant coronary artery stenoses. Patients with three-vessel disease had significantly increased levels of factor XIa-alpha 1 antitrypsin, fibrinogen, and CD62P expression compared to those in other subgroups. Although it is unknown whether these abnormalities are the cause or the result of the vascular lesion, these findings may be important to understand the pathophysiology underlying atherosclerosis or propagation of the atherosclerotic process itself.


The occurrence of saline waters in the Baltic Shield in Sweden is consistent with ongoing but incomplete Holocene flushing and depends on the geometry and connectivity of conductive structures at both regional and local scales, and on the surface topography. Numerical simulation of regional variable-density fluid flow during Holocene land-rise and coastal regression shows that the existence of any old saline water, whether derived from submarine recharge in regions below Sweden's highest postglacial coastline or geochemical processes in the crystalline rock, is an indication either of slow fluid movements through the bedrock over long times, or of long travel distances through fracture systems before arriving at measurement points. During the land-rise period, regional flow is not affected by the variable density of fluids in the upper few kilometers of the shield, and the topography of the water table is the only driving force. The spatial distribution of meteoric flushing water and pre-Holocene waters may be complex, with the possibility of relatively fresh water in fracture zones below salty units even at depths of a few kilometers. The domination of the topographic driving force implies that deep saline water is not necessarily stagnant, and significant flow may be expected to occur in well-connected horizons even at depth. Local topography variation and fracture zone location combine to create a complex flow field in which local topographic driving forces extend to considerable depth in some areas, whereas regional topographic forces predominate in others. Thus, a pattern may be difficult to discern in measurements of the regional salinity distribution, although it is clear that the coastal region is the major zone of discharge for deeper pre-Holocene fluids. During the land-rise period, the regional flow field equilibrates with changing climatic conditions and coastal positions, while the distribution of flushing water and older water lags and will perpetually change between successive glaciations. These characteristics have direct implications for the safety of nuclear water repositories located at depth in Baltic Shield rocks.


Provisions of federal laws that protect reproductive health in the workplace and information on recent federal actions that seek to enhance such protection are reviewed. California's Birth Defects Prevention Act and its Proposition 65, regulatory programs that specifically address reproductive toxicity, also are described.


summary Strongyloidiasis can involve many organs and, therefore, can have unspecific and unusual clinical manifestations, making the infection difficult to diagnose. Further-more, lack of familiarity with this condition can have catastrophic consequences. Due to its unique life cycle, Strongyloides is capable of infecting a host until death of the host. Strongyloidiasis can be a severe disease, caus-ing both hyperinfection syndrome and disseminated disease, particularly in transplantation patients. Thus, any patient who came from or traveled to an endemic area of the world may potentially be infected with this parasite, particularly if symptoms and blood and/or tissue eosino-philia are present. Clinicians should search for strongy-loidiasis in any patient awaiting transplantation who has epidemiologic risk factors or clinical or laboratory signs of the condition. References 1. Liu LX, Weller PF. Strongyloidiasis and other intestinal nematode infections. Infect Dis Clin North Am


The Joint Defence Facility Pine Gap, located just outside the town of Alice Springs in Central Australia and managed by the U.S. National Reconnaissance Office (NRO), is one of the largest U.S. technical intelligence collection facilities in the world.  The corporate presence at Pine Gap has expanded substantially in terms of both the number of companies involved and the total number of civilian contract personnel, and has changed significantly in functional terms, since the 1990s. It includes some of the major US aerospace and defence companies, such as Raytheon, Boeing, Northrop Grumman and General Dynamics, as well as major computer companies, such as IBM and Hewlett-Packard. It also includes an increasing number of 'pure play' companies, who focus almost entirely on contracts from the National Reconnaissance Office, Central Intelligence Agency (CIA) and National Security Agency (NSA), such as Scitor Corporation, SAIC and Leidos.  In addition to the supply of equipment (such as satellite dishes/radomes and computers) and the provision of specialised technical services (such as satellite control and antenna alignment), these companies are now also engaged in a wide variety of management, operations and maintenance roles. While the base is nominally a 'joint' United States-Australian facility, virtually all of the major companies involved are U.S. corporations or their Australian branches – further emphasizing the already heavily asymmetrical character of the 'jointness' of Pine Gap. Moreover, corporations are not necessarily the best or most objective interpreters of US-Australian security and intelligence priorities or Australia's national interests.


Context Controversy remains over the optimal timing of percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI) who have initially been treated with fibrinolytic agents. Objective A meta-analysis of studies was performed comparing immediate or early angiography after fibrinolysis versus a more conservative strategy of deferred PCI or ischaemia-guided management. Data sources MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov Study selection Nine contemporary randomised controlled trials eligible for inclusion enrolling a total of 3325 patients were identified. Follow-up ranged between 1 and 12 months. Data extraction Data were extracted by two independent reviewers using a standard form and cross-checked. Results There was suggestive evidence for a reduction in the risk of total mortality in patients undergoing immediate or early PCI. There were no significant differences in the risk of stroke or major bleeding. Conclusions These results support the current recommendation of a routine early invasive strategy in STEMI patients after successful fibrinolysis.


This study had the purpose to accomplish a bibliographical survey in national journals on experiences of educational practices told by nurses of hospital services. The database used was LILACS and the key words were: continuous education, permanent education and health services. The criteria for the selection of the articles were: to be directly related with the hospital area; to have nurses as main authors; to report results of experiences of educational practices and; to be published from1997 to 2007. The samples consisted of 17 articles. The analysis of the published experiences allows concluding that: the educational practices still follow the logic of the Continuous Education; its planning is not totally complete; there is lack of information on workload, methodological strategies and of evaluation, resources and expected results and; nurses still publishes in an isolated way. The analyzed articles lead to the reflection of a need of transforming educational practices and not just being reproductive of an uncritical performance at the working environment. It does not have to do with excluding Continuous Education activities, but, with the inclusion of practices of Continuous Education in Service in the hospital work environment, with the effective participation of the workers.


These are the stories of the people in Parita Mukta's family, a family which has traversed the continents bearing with it an array of memories and stories, both magical and mythological. The book follows the move of the author's grandparents in the early 1920s from the princely region of Kathiawar in western India (now Gujurat) to the Kenyan colony and spans a period of over eighty years. It tells the history of the children, grandchildren and great-grandchildren of these migrants as they built their lives first in East Africa and then from the 1970s onwards in the cities of London, Ahemdabad, Miami and Toronto. It describes the jostling of a peasant world-view with that of an unbridled financial system. This is not a chronological tale of migration, it is a book set in a universe where magical tales are as tangible as the everyday material world, life-stories becoming entangled with fairy tales and fairy tales informing lives. In stunning lyrical prose Mukta sheds light on the way memories shape the journeys and aspirations of those who have lived in close proximity.


Maize leaf phosphoenolpyruvate carboxylase [PEPC; orthophosphate:oxaloacetate carboxy-lyase (phosphorylating), EC 126.96.36.1991 protein-serine kinase (PEPC-PK) phosphorylates serine-15 of its target enzyme, thus leading to an increase in catalytic activity and a concomitant decrease in malate sensitivity of this cytoplasmic C4 photosynthesis enzyme in the light. We have recently demonstrated that the PEPC-PK activity in maize leaves is slowly, but strikingly, increased in the light and decreased in darkness. In this report, we provide evidence that cycloheximide, an inhibitor of cytoplasmic protein synthesis, when fed to detached leaves of C4 monocots (maize, sorghum) and dicots (Portulaca oleracea) in the dark or light, completely prevents the in vivo light activation of PEPC-PK activity regardless of whether the protein kinase activity is assessed in vivo or in vitro. In contrast, chloramphenicol, an inhibitor of protein synthesis in chloroplasts, has no effect on the light activation of maize PEPC-PK. Similarly, treatment with cycloheximide did not influence the light activation of other photosynthesis-related enzymes in maize, including cytoplasmic sucrose-phosphate synthase and chloroplast stromal NADPH-malate dehydrogenase and pyruvate,P; dikinase. These and related results, in which detached maize leaves were treated simultaneously with cycloheximide and microcystin-LR, a potent in vivo and in vitro inhibitor of the PEPC type 2A protein phosphatase, indicate that short-term protein turnover of the PEPC-PK itself or some other essential component(s) (e.g., a putative protein that modifies this kinase activity) is one of the primary levels in the complex and unique regulatory cascade effecting the reversible light activation/seryl phosphorylation of PEPC in the mesophyll cytoplasm of C4 plants. Light reversibly activates a number of photosynthesisrelated enzymes in plants via several different mechanisms (1-4). Among these is the light activation of leaf cytoplasmic phosphoenolpyruvate carboxylase [PEPC; orthophosphate:oxaloacetate carboxy-lyase (phosphorylating), EC 184.108.40.206] in C4 plants by reversible protein phosphorylation (5, 6). Previous in vitro (7, 8) and in vivo (9) studies with maize leafPEPC demonstrated that the phosphorylation ofa single, N-terminal seryl residue (Ser-15) leads to an increase in catalytic activity and a decrease in feedback inhibition of the target enzyme by L-malate. Related findings from a reconstituted phosphorylation system indicated that the activity of the protein-serine kinase that catalyzes this regulatory phosphorylation of PEPC is not affected by a number of putative, light-modulated cytoplasmic effectors (e.g., reduced thioredoxin h, Ca2+, PPj, fructose 2,6-bisphosphate) and autophosphorylation (6, 7). However, more recent work has established that the phosphoenolpyruvate carboxylase proteinserine kinase (PEPC-PK) is activated by light and inactivated by darkness in vivo (10). Moreover, this striking regulatory process appears independent of SH status, Ca2l levels, and a putative, tight-binding PEPC-PK effector (10). One of the distinguishing features of the reversible light activation of PEPC-PK and its target enzyme, PEPC, in C4 plants is its sluggishness in vivo; when compared to the in vivo activation of photoregulated mesophyll chloroplast stromal enzymes such as pyruvate,Pi dikinase (PPDK) and NADPHmalate dehydrogenase (MDH) (2, 6), the former are both relatively slow processes, taking up to 1 hr, rather than minutes, for completion (10-12). To gain more insight into this difference and the specific mechanism(s) by which the PEPC-PK activity in vivo is slowly, but strikingly, increased in the light and decreased in darkness (10), detached maize leaves were fed two widely used inhibitors of protein synthesis. PEPC-PK activity was subsequently assessed either in vivo [malate IC50 values for inhibition of the target enzyme (11, 12)] or in vitro [32p phosphorylation of purified dark-form PEPC (7, 10)]. Whereas chloramphenicol (CAP), a 70S ribosome-specific inhibitor of chloroplastic protein synthesis, had no effect on the light activation of PEPC-PK, cycloheximide (CHX), an inhibitor of cytoplasmic protein synthesis, completely blocked the light activation of this protein-serine kinase. In contrast, the in vivo activation of several other photoregulated cytoplasmic [sucrose-phosphate synthase (SPS)] and chloroplastic (PPDK, MDH) photosynthesisrelated enzymes was not influenced by CHX treatment. These results indicate that the synthesis and degradation of PEPC-PK per se or some other essential component(s) are involved at one of the primary levels in the regulatory cascade effecting the reversible light activation/seryl phosphorylation ofPEPC in the mesophyll cytoplasm ofC4 plants. MATERIALS AND METHODS Materials. Maize (Zea mays L., cv. Golden Cross Bantam) plants were grown as described (7, 10). [y-32P]ATP [specific activity, 3000 Ci (111 TBq)/mmol] was purchased from Amersham. Dark-form maize leaf PEPC was purified by the procedure described (7, 8). All biochemical reagents were obtained from Sigma except for microcystin-LR (MC) (CalAbbreviations: PEPC, phosphoenolpyruvate carboxylase; PEPCPK, phosphoenolpyruvate carboxylase protein-serine kinase; SPS, sucrose-phosphate synthase; PPDK, pyruvate,P1 dikinase; MDH, NADPH-malate dehydrogenase; CHX, cycloheximide; CAP, chloramphenicol; MC, microcystin-LR. §To whom reprint requests should be addressed at: University of Nebraska-Lincoln, Department of Biochemistry, 210 BcH, East Campus, Lincoln, NE 68583-0718. 2712 The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact. Proc. Natl. Acad. Sci. USA 88 (1991) 2713 biochem). Stock solutions of 10 mM CHX and 310 mM CAP were prepared in absolute ethanol, while 0.5 mM MC was dissolved in 20% (vol/vol) methanol. Feeding of Protein Synthesis and Protein Phosphatase Inhibitors. Preilluminated leaves (-2 g fresh wt each) from 4to 6-week-old maize plants were excised underwater, inserted into 150-ml beakers containing 100 ml of distilled water (control), 5 ILM CHX, 310 ,uM CAP, or 10 nM MC in water and maintained at room temperature. When feeding was done in the dark, the beakers were placed in a darkened fume hood overnight. The dark sample was then prepared from these leaves and the corresponding light sample was collected after a 90-min illumination of the tissue. When feeding was done in the light, detached control leaves that had been preilluminated for 1.5 hr in water were either maintained in water or fed inhibitors for 4 hr in continued light, followed by preparation of leaf extracts. Illumination was provided by a forced-air cooled 300-W, low-temperature lamp at an incident light intensity of 600-800 /iE m 2 s-' (E, einstein) (400-700 nm). Preparation of Leaf Extracts. Samples (0.3 g fresh wt) from the control or inhibitor-treated leaf material were chopped and ground at 40C in a prechilled mortar containing washed sand, 2% (wt/vol) insoluble polyvinylpyrrolidone, and 1.5 ml of the appropriate extraction buffer. Buffer A [0.1 M Tris HC1, pH 8.0/20% (vol/vol) glycerol/10 mM MgCl2/14 mM 2-mercaptoethanol/1 mM EDTA] was used for preparation ofPEPC and its protein-serine kinase; buffer B (buffer A plus 2 mM pyruvate) was used for PPDK; buffer C (50mM Mops-NaOH, pH 7.5/15 mM MgCl2/2.5 mM dithiothreitol/1 mM EDTA/0.1% Triton X-100) was used for SPS; and buffer D (0.1 M Tris-HCl, pH 8.0/1 mM EDTA/14 mM 2-mercaptoethanol) was used for MDH. The crude leaf homogenates were filtered through an 80-,tm nylon net and centrifuged for 1.5 min at 8700 x g. The supernatant fluid was either used immediately (PPDK, MDH) or after a 0.2-ml aliquot was rapidly desalted at 4°C on a Sephadex G-25 column (1 x 5 cm) equilibrated with 0.1 M Tris-HCI, pH 7.5/10 mM MgCI2/20% (vol/vol) glycerol for PEPC and PEPC-PK or buffer C minus Triton X-100 for SPS. Activity Assays. PEPC activity was determined spectrophotometrically at 340 nm and 30°C. The assay mixture (12) contained, in a total vol of 1 ml, 50mM Hepes-KOH (pH 7.3), 2.5 mM phosphoenolpyruvate, 5 mM MgCI2, 1 mM NaHCO3, 0.2 mM NADH, 10 units of malate dehydrogenase, various concentrations of L-malate, and 10 ,ul of desalted extract (added last). Malate IC50 values were taken as the malate concentration required for 50%o inhibition of PEPC activity under these assay conditions. PEPC-PK activity was measured by 32p incorporation from [y32P]ATP into purified dark-form PEPC (10). The phosphorylation mixture contained 35 ,ul of desalted extract, 10 ug of purified dark-form maize PEPC, an adenylate kinase inhibitor plus a creatine kinase/phosphocreatine ADP-scavenging system (10), 25 ,uM ATP, and 3 ,Ci of [y-32P]ATP in a final vol of60 p1. After 45 min of incubation at 30°C, the reaction was stopped by adding 20 ,ud of SDS sample buffer (0.25 M Tris-HCl, pH 6.8/8% SDS/40o glycerol/20% 2-mercaptoethanol), followed by immediate boiling for 2 min. Vertical SDS/PAGE was performed as described (13, 14), and autoradiographs were prepared from the dried gels with Kodak X-Omat AR film and two Lightning Plus intensifying screens (DuPont) at -800C. SPS, PPDK, andMDH activities were measured according to ref. 15 (at limiting substrate concentrations plus 10 mM P1 at 250C), ref. 16 (forward direction plus 2.5 mM glucose 6-phosphate and 2 units of purified maize PEPC at 300C), and ref. 17 at 30TC, respectively. RESULTS AND DISCUSSION Effects of CHX, CAP, and MC on the Light-Induced Changes in Malate Sensitivity of Maize Leaf PEPC. The IC50 values for PEPC inhibition by L-malate were used as an indirect means of following the effect of dark to light transitions on the apparent in vivo activity of the PEPC-PK since these values reflect the seryl-phosphorylation status of the target enzyme both in vitro (7, 8) and in vi


Desmoid tumors, also known as aggressive fibromatosis, are fibromuscular neoplasms that arise from mesenchymal cell lines. They may occur in almost all soft tissue compartments. Primary desmoids of the small bowel are rare but potentially serious tumors presenting unique challenges to the general surgeon. We present one case of a 59-year-old man presenting with three months of abdominal distension secondary to a small bowel desmoid. Computed tomography of the abdomen showed an 18-cm mass in the mid-abdomen without obvious vital structure encasement. Percutaneous biopsy of the mass indicated a desmoid tumor. The patient underwent a successful elective exploratory laparotomy with resection and primary enteric anastomosis. Final pathology revealed the mass to be a primary desmoid of the small bowel. His post-operative course was uneventful. At two years after surgery, he is symptom free, and there is no evidence of disease recurrence. Due to the rare nature of primary small bowel desmoids, there are few specific care pathways outlined. This is a challenging pathology to treat that often requires a multidisciplinary team of surgical and medical oncologists.


The complement of glucan-hydrolysing enzymes produced by yeast species is considered to be relevant to morphogenesis, since this polysaccharide is the major structural component of the yeast cell wall. beta-glucanase systems of different species consist of both 1,3-beta- and 1,6-beta-hydrolases, which exert their action by either an exo- or an endo-splitting mechanism. The diversity of beta-glucanase systems, even among related species, is striking. The enzymes are produced for export, and the active forms of some of them seem to be generated upon secretion. Genetic approaches and the cloning of the glucanase genes are being used to clarify the biological role of the different enzymes. These also offer a possibility for genetic analysis of the functions related to cell wall dynamics with potential applications in biotechnology.


............................................................................................................. iii DEDICATION .......................................................................................................... v ACKNOWLEDGEMENTS ...................................................................................... vi NOMENCLATURE.................................................................................................. vii TABLE OF CONTENTS .......................................................................................... viii LIST OF FIGURES................................................................................................... x LIST OF TABLES .................................................................................................... xii


Estimation of upward heat losses is required for design or thermal performance evaluation of a flat plate collector. Collectors with vertical configuration are used at high latitudes and are integrated with building walls. Values of glass cover temperature are required for calculation of upward heat losses under different operating conditions. Glass cover temperature can be determined from numerical solution of heat balance equations. In the present work an empirical relation for glass cover temperature of a single glazed flat plate collector for angle of tilt 60 to 90 degree is proposed. Values of glass cover temperature obtained from this empirical relation have been used for computation of top heat loss coefficient of flat plate collector. Analytical equation has been employed for estimation of Ut . The range of variables covered in the present analysis is 20 °C to 150 °C for absorber plate temperature, 0.1 to 0.95 for absorber coating emittance, 20 mm to 50 mm for air gap spacing, 60 deg to 90 deg for collector tilt, 5 W/m2 K to 30 W/m2 K for wind heat transfer coefficient and −10 °C to + 40 °C for ambient temperature. The maximum absolute error in values of Ut is within two percent in comparison to values obtained by numerical solution of heat balance equations over the entire range of variables covered in the present work.Copyright © 2010 by ASME


eScholarship provides open access, scholarly publishing services to the University of California and delivers a dynamic research platform to scholars worldwide. Abstract: Many urban planners promote mixed-use developments as one component of a broader sustainable development strategy. Scholars and advocates argue that these neighborhoods have the potential to reduce traffic congestion by promoting fewer trips, shorter travel distances, and alternative modes of travel. With their mix of ethnic residents, businesses, services, and community institutions, many ethnic neighborhoods are mixed-use neighborhoods. We hypothesize, therefore, that residents of these ethnic neighborhoods will exhibit different travel behavior than those living outside of ethnic neighborhoods. Drawing on data from the 2000 U.S. Census, we examine whether residents of ethnic neighborhoods are more likely to commute by carpool and public transit than other workers. We find a significant relationship between residential location in ethnic clusters and travel behavior. The findings provide insight into the relationship among social networks, land use, and travel behavior. ABSTRACT Many urban planners promote mixed-use developments as one component of a broader sustainable development strategy. Scholars and advocates argue that these neighborhoods have the potential to reduce traffic congestion by promoting fewer trips, shorter travel distances, and alternative modes of travel. With their mix of ethnic residents, businesses, services, and community institutions, many ethnic neighborhoods are mixed-use neighborhoods. We hypothesize, therefore, that residents of these ethnic neighborhoods will exhibit different travel behavior than those living outside of ethnic neighborhoods. Drawing on data from the 2000 U.S. Census, we examine whether residents of ethnic neighborhoods are more likely to commute by carpool and public transit than other workers. We find a significant relationship between residential location in ethnic clusters and travel behavior. The findings provide insight into the relationship among social networks, land use, and travel behavior.


The oil industry is experiencing a critical situation as the Covid-19 pandemic outbreak. There are several challenges that facing the industry specially the investors as the global decline in demand for Energy merchandises, the future exploration and development drilling in new assets that require massive investments is still uncertain based on the current market price and conditions. The much-reported fall in oil prices and the acute pressure on IOCs to survive in this environment led the companies to stop many ongoing projects and shrink work profile that affected the oil production all over the world.
 The situation in Egypt is quite challenging for the investors as Egypt is a big consumer, along with the political stability that kept the economy running directed the big IOCs to embrace innovative approaches to lower the operating costs that has the direct impact on the cost per barrel to support maintaining the country growth and secure current energy demand.
 Dragon Oil company as newly introduced to Egypt's market after acquiring the market shares of one of the major joint ventures in Egypt (Gulf of Suez Petroleum Company- GUPCO) in October 2019 has faced the same dilemma of exerted pressure on the expenditures (Capex and Opex) in order to cope with the global market circumstances. However that didn't deter the company to embrace an innovative way of thinking and handling for the situation.
 Dragon Oil/GUPCO multi-disciplinary teams achieved successfully a production incremental increase of 10,000 barrels per day through the past six month by adapting a strategic management innovative plans, alternative lower cost technical solutions, production optimization and introducing new proved technologies to the 50 years old assets.
 This paper will highlight the complete workflow adopted by GUPCO/Dragon Oil teams covering the whole process aspects; appraise, select, define and execution phases to achieve the company goals. The work done was including restoring production from Shut-in offshore platforms or wells via fixing the surface network using neoteric solutions, widely applying rigless interventions using several new techniques in the current producers to maximize their production and optimizing the production cycle across the four production chokes
 In Summary, Dragon Oil/GUPCO teams managed to increase GUPCO's production despite of the restricted budget and the negative impact of COVID-19 pandemic on the oil price and reach an outstanding performance in operation excellence and safety aspects that results in arresting the natural decline and increase the growth production by about 15% from the 2019 Average production.


Population-based evidence suggests that the prevalence of psychotic symptoms varies with ethnicity. However, the validity of these self-reported experiences, both as measures of psychotic symptoms per se and as measures of ethnic variation in risk for reporting these symptoms, is questionable. Cultural background and social position may affect the experience and expression of symptoms, which may in turn affect their measurement in survey research. This thesis explores these issues by assessing the psychometric properties of psychosis screening instruments as measures of ethnic differences in psychosis risk in two contexts, Great Britain and the United States. Following this, differences in risk for reporting psychotic symptoms were examined in the context of the varying social and economic conditions to which different ethnic groups and migrant generations are exposed.This was accomplished in the following way: Firstly, the prevalence of self-reported psychotic symptoms was examined across ethnic and generational groups in two large samples of British and American populations; Secondly, the construct validity of the instruments was assessed by means of exploratory and confirmatory factor analyses of response to their symptom indicators. The concurrent validity of the symptoms with measures of self-perceived cognitive and social dysfunction was then examined in a structural equation modeling framework; Thirdly, the cross-ethnic and cross-generational validity of response to these screening instruments was assessed in a multiple-group confirmatory factor analysis framework in which in which the psychometric characteristics of the instruments were compared; And finally, ethnic and generational differences in risk for reporting psychotic symptoms were examined in the context of differential exposure to racial discrimination.Both instruments had construct validity in their measurement of psychotic symptoms, with the exception of one item in the British instrument, as well as concurrent validity with measures of self-perceived cognitive or social dysfunction. The British instrument performed adequately in the measurement of psychotic symptoms across ethnic groups, but did not across migrant generations. The American instrument performed adequately in the measurement of psychotic symptoms across generations, but not across ethnic groups. The effect of measurement noninvariance on the estimation of risk across groups was, however, modest in size. Finally, there was evidence for risk of reporting psychotic symptoms being raised among those who were exposed to racial discrimination.These findings suggest that these self-reported psychotic symptoms constitute clinically relevant phenomena which appear phenotypically similar to the clinical symptoms in diagnosed psychotic disorder. Risk is distributed unevenly over ethnic groups in Britain and the US, is higher among minorities who were exposed to social adversity, and higher among the second generation (in most cases). These patterns are, therefore, highly suggestive of social causation in the aetiology of these self-reported symptoms.


A survey was conducted in August 2008 to determine the distribution and extent of stalked diatoms in major rivers and streams in Grand Teton National Park (GTNP). We determined that a nuisance bloom of the diatom Didymosphenia geminata was present in Lake Creek from the outlet of Phelps Lake to approximately 1 km downstream of the Rockefeller Preserve. This bloom was considered "excessive" because the coverage of the stream substrate was 70% or above for greater than 1 km. This diatom species is able to survive out of water in damp conditions, and it may be transported on the gear of recreationalists. In GTNP, this diatom was found in a high visitor use area, with concomitant potential for the species to be spread by anglers to other sites within the national park. Although there are several factors that appear to influence its distribution, recent nuisance blooms of this species suggest popular angling sites are often sites of nuisance blooms. Decontamination of aquatic gear by recreationalists may be appropriate to limit the spread of nuisance blooms within the national park system and adjacent public and private water bodies.


We study the impact of corporate networks on the takeover process. We find that better connected companies are more active bidders. When a bidder and a target have one or more directors in common, the probability that the takeover transaction will be successfully completed augments, and the duration of the negotiations is shorter. Connected targets more frequently accept offers that involve equity. Directors of the target firm (who are not interlocked) have a better chance to be invited to the board of the combined firm in connected M&As. While connections have a clear impact on the takeover strategy and process, we do not find evidence that the market acknowledges connections between bidders and targets as the announcement returns are not statistically different from those bidders and targets which are ex ante not connected.


The hygiene hypothesis assumes a low incidence of allergic diseases in families engaging in farming work. However, a few studies have indicated rural life as a potential risk factor for atopic dermatitis (AD). Using a large Japanese birth cohort dataset, we calculated the accumulated incidence of AD in children aged 6 months and 1, 2, and 3 years by family business and the hazard ratio. We adjusted for confounding factors. The father's job was considered the family business. We analysed data on 41,469 father–child pairs at 6 months of age, 40,067 pairs at 1 year, 38,286 pairs at 2 years, and 36,570 pairs at 3 years. We found the highest accumulated incidence of AD among children with fathers engaged in primary industry, with 2.5% at the age of 6 months, 6.6% at 1 year, 12.0% at 2 years, and 15.4% at 3 years. Among primary industry occupations, forestry was associated with the highest incidence of AD across these ages. The hazard ratio of AD was also highest for children whose family business was primary industry. In conclusion, the highest incidence and hazard ratio of AD were observed among children whose fathers worked in primary industry.


Little research has been done on Western women who convert to Shi'i Islam. To fill this gap, this study was conducted on American and Canadian women who have converted to Shi'i Islam. Most of the research subjects in this study reported a moderate to severe sense of social marginalization after conversion. This marginalization resulted from membership in multiple minority groups (Shi'i, Muslim, convert, and female); Black converts reported the most severe sense of marginalization due to the added pressure of being a racial minority in North America. Most of the research subjects also experienced a sense of social exclusion from other Shi'i Muslims. Therefore, the question arises as to why these women continued to adhere to Shi'i Islam despite these difficulties. This article will attempt to answer this question through an analysis of the data provided by the research subjects.


ROS1 gene arrangements occur in approximately 1% to 2% of non-small cell lung cancers. Crizotinib, the ROS1-tyrosine kinase inhibitor (TKI), has been approved for ROS1-rearranged lung cancer based on its dramatic therapeutic effect, but cures are usually not achieved. We have been focused on relationships between Yes associated protein1 (YAP1) and resistance to molecular target drugs. YAP1, a main mediator of the Hippo pathway, promotes cell proliferation and epithelial-mesenchymal transition and is associated with drug resistance in some cancer types. We previously demonstrated that YAP1 mediates survival against alectinib therapy in anaplastic lymphoma kinase-rearranged lung cancer cells. Then, in this study, we evaluated the role of YAP1 as an initial survival mechanism from lorlatinib in ROS1-rearranged lung cancer. We established a patient-derived EZR-ROS1-rearranged lung cancer cell line (KTOR71) from pleural effusion of a patient who acquired resistance to crizotinib. Subsequently, we conducted functional analysis of YAP1 involvement in drug-resistance, using this patient-derived cell line. DNA sequencing confirmed that KTOR71 cells harbored EZR-ROS1 fusion and ROS1 S1986F mutation, which is known crizotinib resistance mutation. KTOR71 cells were sensitive to lorlatinib, while resistant to crizotinib in cell viability assay (CVA). Nuclear localization of YAP1, which is an activation marker of YAP1, was assessed using immunofluorescence staining. In KTOR71 cells, YAP1 was activated after lorlatinib exposure. Then, to evaluate functional role of YAP1 in the initial survival against lorlatinib, the genetic inhibition of YAP1 in KTOR71 cells were performed using small interfering RNA (siRNA). Silencing of YAP1 by siRNA enhanced sensitivity to lorlatinib in KTOR71 cells in CVA. Furthermore, to confirm this functional role of YAP1 in vivo, we established the KTOR71 cell-derived xenograft model. The combination therapy with lorlatinib and verteporfin, an inhibitor of YAP1-TEAD interaction, sustained tumor remission significantly compared with lorlatinib monotherapy in vivo. Finally, we found that AKT was reactivated with activation of YAP1 and silencing of YAP1 by siRNA suppressed this AKT reactivation. These results suggest that YAP1 may be a potential drug target for ROS1-rearranged lung cancer. Citation Format: Masatoshi Yamazoe, Hiroaki Ozasa, Tetsuya Ohgimoto, Kazutaka Hosoya, Hitomi Ajimizu, Tomoko Funazo, Yuto Yasuda, Takahiro Tsuji, Hironori Yoshida, Ryo Itotani, Yuichi Sakamori, Young Hak Kim, Hirai Toyohiro. Activation of YAP1 confers ROS1 inhibitor resistance in ROS1-rearranged lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1098.


The Web is essential for education and e-learning. This situation has been boosted by migration to distance education due to the SARS-Co V-2. However, students with disabilities have been seriously affected because online teaching is very often not accessible. For this reason, this research aims to evaluate the accessibility of the homepages of the web portals of the Ecuadorian higher education institutions ranked in the Webometrics with the Web Content Accessibility Guidelines (WCAG) 2.1 of the World Wide Web Consortium. The results obtained determined that the 65 homepages analyzed of the web portals have accessibility errors. Therefore, we concluded that we should adopt the WCAG in the web sites to comply with the Ecuadorian technical regulation RTE INEN 288 "Accessibility for web content."


Four years ago, we introduced the use of Castelli membrane tubes into our practice. Although initial reports in the literature and restrictions on indications from the manufacturer on use were extremely cautionary, we were able, by careful intraoperative technique and the use of postoperative antibiotics, to expand the use of the membrane tube and offer it to our entire patient population. To document this, we used a prospective study of 124 consecutive ears receiving a membrane tube. Follow-up study included clinical, audiometric, and tympanometric evaluation. We found the membrane tube to function extremely well in an extremely high percentage of ears, regardless of whether the ear contains serous or mucoid fluid. The advantages of membrane tubes include the lack of special care required, resultant high patient and parental acceptance, and the low incidence of draining ears with tubes in place.


The article discusses a number of pressing problems related to the functioning of institutions of the President of the United States. It studies and analyzes the sources of presidential power, the theory of checks and balances, and provides an overview and assessment of the terminology of the topic. The author examines the legal nature of the presidency and the relationship of Congress and the President of the United States. Furthermore, he analyzes the role of U.S. Supreme Court decisions in determining the place and role of the President within the framework of the legal system.


An ongoing challenge in physics is to make increasingly accurate measurements of physical quantities. Bose–Einstein condensates in atomic gases are ideal candidates for use in precision measurement schemes since they are extremely cold and have laser-like coherence properties. In this paper, we review these two attributes and discuss how they could be exploited to improve the resolution in a range of different measurements.


In consideration of security and banning minors from Internet bars, there's a need to monitor Internet surfing personnel in Internet bars. Common monitoring systems invariably achieve this goal by installing specialized equipments and dedicated hardware. The monitoring system discussed in this paper takes advantage of the general existing equipments in most Internet bars, i.e. computer's USB cameras, to realize the same function, therefore it costs much less. The key technique in the implementation of this system is developing USB device filtering driver on the base of WDM mode. A USB camera' function is extended by developing its filtering driver and thus it could provide the service for the monitoring system. In this paper, the overall design and key technique of the system is discussed.


The high grey-flannel fog of winter closed off the Salinas Valley from the sky and from all the rest of the world. On every side it sat like a lid on the mountains and made of the great valley a closed pot. On the broad, level land floor the gang plows bit deep and left the black earth shining like metal where the shares had cut. On the foothill ranches across the Salinas River, the yellow stubble fields seemed to be bathed in pale cold sunshine, but there was no sunshine in the valley now in December. The thick willow scrub along the river flamed with sharp and positive yellow leaves.


What kind of explanation does history promote? Does history give us an advantage in dealing with current as well as bygone problems? These two different questions assume very similar burdens when historians defend the "usefulness" of their writing and research. The demand that history be "useful" impinges especially hard on the profession today in the areas of educational and black history. The reasons are, or should be, obvious. What is less obvious at the moment is which of the many meanings of "useful" do historians find most compelling. In the past, the professional and educational role of the historian has been largely affected by the questions he poses to deal with in the "usefulness" of his discipline.


This study aimed to identify evidence of validity for the Test of Nonverbal Intelligence – TONI 3 - Form A in the evaluation of the intellectual ability of people with Down Syndrome (DS). It comprises 51 people with the syndrome, of both sexes, ages ranging from 6 to 24 (M=15.3; SD =4.9), coming from institutes for special education in the interior of the state of Sao Paulo. The test was administered individually and the results showed evidence that confirms the reliability of the TONI 3 - Form A for the assessment of developmental abilities. Similar to what was observed in the normative sample, the average score was higher in subgroups formed by people with higher average age, though there have been oscillations in the score of some age groups in which the people with DS were divided. There was no significant statistical difference between the results obtained with the normative sample and the people with Down Syndrome, which suggests the usefulness of other similar studies, to be carried out with bigger samples, aiming to identify patterns of cognitive ability development in people with Down Syndrome.


The article deals with the role of the United States in forming military doctrine of Japan from 1945 to 2010. The article also examined the influence of Samurai military tradition on military and ideological training of Japanese army and Navy since the late 19th to mid 20th century, the history of development of strategic relations between the United States and Japan after the Second World War in military, economic and political fields. Documents on political and economic development of Japan from 1945 to the present day have been explored; factors which have had a huge impact on the formation of a new military doctrine have been examined.


This article presents a technique based on the JBIG algorithm for binary shape coding in both lossless and lossy modes. Because it is applied directly to the bitmap representing the shape information, it bypasses the overhead in computation of an intermediate contour representation and its associated conversions. This leads to a simpler algorithm which is more suitable for a larger class of shape data. In addition a mechanism is proposed which allows a rate control for lossy coding mode.


Electron spin resonance provides a specific and sensitive method of studying para-magnetic free atoms in gases at low pressures. We are using this technique to study the reactions of free oxygen atoms and hydrogen atoms with simple hydrocarbons using an X–band superheterodyne spectrometer (Coates 1964; Brown 1966) with a TE102 mode cavity. With this arrangement, only atoms (which have magnetic dipole transitions) can be detected, the smallness of the magnet available has prevented the use of a cavity which was also suitable for the electric dipole transitions of diatomic radicals. Magnetic field modulation at 33 c/s is used and the signal recorded in differential form by phase sensitive detection at 33 c/s. Transitions of molecular oxygen are used to calibrate the sensitivity at regular intervals (Krongelb & Strandberg 1959; Westenberg & de Haas 1964), this calibration was checked by measuring the oxygen atoms produced in the stoichiometric titration of active nitrogen with known flows of nitric oxide. All the reactions studied to date are first order in free atom concentration, therefore only relative concentrations are needed except in determining the overall stoichiometry. It was found that the peak-to-peak height of the differential display and its first moment were strictly proportional to each other for both oxygen atoms and hydrogen atoms at constant total pressure (figure 1) providing the usual precautions were taken to avoid line distortion and power saturation. Nitrogen atoms, which give very narrow lines and have a long spin relaxation time, need particular care. The design and operation of the flow system call for some comment. A 10 mm diameter quartz flow tube is used with a fixed distance of about 1 m between the discharge and the measuring cavity (figure 2). For typical total pressures around 2 mmHg, a 50 W microwave discharge gives about 1% of free atoms (i. e. 10-9 g atom cm-3 or 6 x 1014 atoms cm-3). Concentrations of hydrogen atoms are measured down to 10-11 g atom cm-3 (6 x 1012 atoms cm-3), the limit of detection being smaller than this by about a factor of 10. A movable probe permits the introduction of varying amounts of reactants at different points upstream from the measuring cavity. The change of atom concentration at the cavity is then wholly due to the reaction being studied, and the loss of atoms by parallel processes such as recombination on the walls of the flow tube is automatically cancelled, providing it and the reaction studied are both first order in free atoms (Clyne & Thrush 1963). This condition is fulfilled for the surface recombination of oxygen atoms and hydrogen atoms. The above relation holds even if the surface recombination is not uniform (Hartley & Thrush 1967). Since all runs can start from the same measured atom concentration irrespective of the reaction time and reactant concentration chosen, the reproducibility and drift of the spectrometer and flow system can be checked frequently. Under favourable conditions, spectrometer reproducibility approaches 3%.


Automatically translating images to texts involves image scene understanding and language modeling. In this paper, we propose a novel model, termed RefineCap, that refines the output vocabulary of the language decoder using decoder-guided visual semantics, and implicitly learns the mapping between visual tag words and images. The proposed Visual-Concept Refinement method can allow the generator to attend to semantic details in the image, thereby generating more semantically descriptive captions. Our model achieves superior performance on the MS-COCO dataset in comparison with previous visual-concept based models.


The epidemiologic data demonstrated by SEER clearly show a decrease of cervical cancer over the decades due to widespread cervical cancer screening with a pap smear, although there is currently a shift in the age distribution resulting in an increase of cervical cancer among younger women, and a lower screening rate is a problem, particularly in Japan. Another peculiar trend is an increase of endocervical adenocarcinomas, and the underlying cause of this trend is still unknown. A screening program, employing the Bethesda system terminology and liquid-based cytology, combined with HPV DNA testing and p16(INK4a) immunohistochemistry/ cytochemistry, and a management guideline proposed by ASCCP, has been contributing to the early detection of cervical cancers. However, it should be kept in mind that an HPV-targeted strategy is effective only for squamous lesions, which is mostly HPV-driven neoplasms, and that unusual HPV-negative adenocarcinomas, including gastric, clear cell, and mesonephric types, are a pitfall of HPV DNA testing and vaccination. Therefore, potential biomarkers, which can be applied for both squamous and glandular lesions, are awaited. The gastric type of adenocarcinoma of the cervix, a recently described subtype, is a distinct entity showing an aggressive clinical behavior, and, importantly, is estimated to be more frequent than in western countries.


Although the scientific evidence is not entirely supportive, atypical antipsychotics have been used widely for the treatment of children and adolescents with mental illnesses as alternatives to typical antipsychotics which have more serious unwanted adverse effects than atypical neuroleptics. On the basis of clinical experiences and research data, atypical antipsychotics have been prescribed for adolescents with schizophrenia, manic or mixed episodes of bipolar disorders, tic disorders, aberrant behaviors in pervasive developmental disorders, and impulsive or violent behaviors in disruptive behavior disorders. Due to their efficacy and relatively more tolerable side effects, the use of atypical antipsychotics has become increasingly popular in child and adolescent psychiatry. However, we should pay attention to the limitations associated with short-term clinical experiences and the lack of well-designed controlled studies, especially in terms of adverse effects including those involving metabolic processes.


Describes an application of fuzzy set theory to real problems. The problems we study refer to concepts, policies, strategies and techniques of total quality management used in industrial enterprises and also service companies. More specifically, the paper focuses on the quality evaluation process applied in these institutions in order to verify if the quality of their processes, products, services and general resources (mainly human resources) are reaching better levels. The paper utilizes parameters and criteria from the National Brazilian Quality Award as a reference. The obtained results show the theoretical and practical adjustment of fuzzy sets to the general quality evaluation model under study.


An electromagnetic pulse (EMP) explodes in real-time and causes critical damage within a short period to not only electric devices, but also to national infrastructures. In terms of EMP shielding rooms, metal plate has been used due to its excellent shielding effectiveness (SE). However, it has difficulties in manufacturing, as the fabrication of welded parts of metal plates and the cost of construction are non-economical. The objective of this study is to examine the applicability of the arc thermal metal spraying (ATMS) method as a new EMP shielding method to replace metal plate. The experimental parameters, metal types (Cu, Zn-Al), and coating thickness (100–700 μm) used for the ATMS method were considered. As an experiment, a SE test against an EMP in the range of 103 to 1010 Hz was conducted. Results showed that the ATMS coating with Zn-Al had similar shielding performance in comparison with metal plate. In conclusion, the ATMS method is judged to have a high possibility of actual application as a new EMP shielding material.


In the current study, twin wind blades are designed, fabricated and the effect of various gap ratio (g*) at various angle of attacks (α) on a next to each other twin wind blades are examined in an openchannel wind tunnel. Aerodynamic forces and moments are determined by using three-constraint force balancer. For gap ratio of zero, the aerodynamic attributes are like those of a solitary wind blade edge. As g* increases, these two wind blades actuate the vertical wake to stage vortex shedding modes. With further increment in g*, the wake stream pattern was like those behind a solitary wind blade. For a solitary wind blade, the maximum lift is found to be at α = 30. The pitching moment increases with α. The impact of upper aerofoil blade on the lower one diminished as g* increases. doi: 10.5829/ije.2018.31.05b.18


Piper methysticum leaf/root/stem extract is the cosmetic ingredient name for a material derived from the leaves, roots, and stems of the Piper methysticum G. Forster plant, commonly known as kava kava. This and other kava-derived ingredients are used as skin-conditioning agents at concentrations from 0.0001% to 0.1%. The Food and Drug Administration issued a consumer advisory in 2002 expressing concern about liver damage in individuals who have ingested kava products. The available oral toxicity data support the concern about liver damage on ingestion but do not resolve the question, for example, whether these ingredients would be substantially absorbed through the skin. Other data needs are described, including toxicology data for yangonin, methysticin, and kavain, which may be present in kava-derived ingredients. Accordingly, the available data are insufficient to support the safety of these ingredients in cosmetics.


Introduction: Chronic kidney failure in India and around the world is a significant health problem. The most effective and affordable treatment may require screening for early detection,intervention and prevention. Public awareness is a key determinant to overcome the burden of Chronic Kidney Disease(CKD). However, there is a lack of information on CKD among South Indian people. Aim: To assess the awareness and knowledge of CKD among the South Indian population. Materials and Methods: A questionnaire-based cross-sectional study was conducted through an online form; the questions were generally based on the physiological role of kidney and awareness questions related to CKD. The sample size was 500 participants, of age >18 years and snowball sampling method was implemented. Among the study population, 68 participants had a family history of CKD and they were excluded. The data were analysed through Pearson Chi-Square test. Results: The mean knowledge score was 13 (SD±5.0), with values ranging from 0 to 22. The mean age of the population was 47.80±8.5 years. Multiple regression on demographic data and knowledge yielded statistically negligible results.The study population included 432 participants and the result showed the realms that most responded incorrectly were physiology of kidney, CKD symptoms, risk factors and the domain of testing and diagnosis. Conclusion: The participants had ample knowledge of the risk factors, signs and symptoms of CKD and insufficient knowledge of the physiological function of the kidney and the diagnosis of CKD. Therefore, efforts are necessary to create awareness and educate people about the early detection and prevention of CKD.


There are two microtubule-microfilament systems in the posterior silk gland cells of Bombyx mori. One is a radial microtubule system; the other is a circular microtubule-microfilament system. These two systems are presumably concerned with the intracellular transport of secretory granules of fibroin and the secretion of fibroin into the lumen, respectively. Conventional and scanning electron microscopic observations of the two microtubule-microfilament systems in the posterior silk gland cells are reported. Scanning electron micrographs showed that a number of parallel linear cytoplasmic processes ran circularly on the luminal surface of the posterior silk gland cells. These processes were assumed to correspond to the circular microtubule-microfilament systems. The effects of cytochalasin (B or D), a secretion stimulating agent of fibroin, on the intracellular recording of membrane potential from the posterior silk gland cells are also reported. Exposure to cytochalasin resulted in depolarization of the membrane potential of the gland cells. Possible functional roles of the two microtubule-microfilament systems in the secretory mechanism of fibroin are discussed with reference to the effects of antimitotic reagents and cytochalasin on these two systems.


This paper presents a system that retrieves descriptive phrases of proper nouns from free text. Sentences holding the specified noun are ranked using a technique based on pattern matching, word counting, and sentence location. No domain specific knowledge is used. Experiments show the system able to rank highly those sentences that contain phrases describing or defining the query noun. In contrast to existing methods, this system does not use parsing techniques but still achieves high levels of accuracy. From the results of a large-scale experiment, it is speculated that the success of this simpler method is due to the high quantities of free text being searched. Parallels between this work and recent findings in the very large corpus track of TREC are drawn.


Abstract : The general objective of the proposed research was to determine how reasoning ability, or intellectual capacity, affects gain in reading ability. The theory underlying the present research was that poor readers consist of two types--those who read poorly because of deficits in their reasoning ability and those who read poorly because of deficits in reading practice, or experience. The effect of reading practice upon reading ability was investigated using high school students who read poorly. The reading training involved a recently developed technique, called programmed prose, which allows regular reading material to be automatically converted into training material. A PLATO IV computer terminal was used to administer the programmed prose passages. Each student was given 50 to 70 hours of individualized instruction on the terminal. There were three separate studies with six high school students in each study. All students were at about grade level 5 in reading ability prior to the instruction. One half of the students in each study were selected because they purportedly had high reasoning ability, as indicated by high scores on the Raven Progressive Matrices Test; the other one half had low scores on this test. The results were consistent across all three studies. The high Raven groups, who supposedly had high reasoning ability and should benefit greatly from reading training, did not gain more than the low Raven groups. When gain in reading ability was measured using a test that was just like the task employed in the reading training, there was a large amount of gain--from grade level 5 to 8.


Valine, leucine, and isoleucine were extracted by the lactating bovine mammary gland in excess of outputs in milk protein. Carbon-14 uniformly labeled L-valine, L-leucine or L-isoleucine were catabolized when incubated in vitro with lactating bovine mammary tissue slices. The pathways of degradation of these amino acids by mammary tissue appear to be those common to other tissues. These amino acids represent a potential source of energy to the mammary gland as well as a source of carbon and alpha-amino nitrogen for synthesis of nonessential amino acids.


Our aim is to provide the Rapid Entire Body Assessment for computer operator, this review is convenience for assessment of jobs in various professions like construction, health care jobs and workshops, etc. The computer technology is growing in daily life, computer is operated by user for a longer time so, sitting posture should be taken care by the operator if not it may lead to harmful effect for the body such as body ache, neck pain, pain in the spinal cord, various disorder relating to change in eye pressure and also there may occur a vision related problem caused by continuous use of computer for longer duration of time and also work stress will cause incardiovascular diseases so, the computer operators can protect themselves from those health issues by implementing good body posture by the use of sensors and communication devices we can continuously monitor the computer operator for the betterment of sitting posture of human body. The Arduino UNO microcontroller board is based on the Atmega328 is used. Eye blink sensor is used to avoid eye pressure by continuously monitoring the eye, Flex sensor is used to access the bending information of the knee, the angles and positioning can be matched with the computer is analysed through accelerometer. All these alerts are provided through audio and display system. Key points: Arduino Uno, flex sensor, eye blink sensor, accelerometer sensor, audio and display system.


Leg muscles are generally viewed as motors, contracting and relaxing to drive legs up, forward, and down. But new results reported on page 1113 challenge the long-standing assumption that muscles always do actual work, shortening against resistance to propel an animal forward. By directly monitoring a leg muscle in turkeys running on a treadmill, researchers have now found that the muscle hardly contracts at all, at least when the animals run on level ground. Instead, it shortens slightly before the foot is planted to exert the force needed to keep the tendon attaching the muscle to the heel stretched while the foot is on the ground, thus storing energy for the next stride. As a result, the muscle does very little work.


Author(s): Chan, Wei-Ting | Advisor(s): Kahng, Andrew B. | Abstract: In the past decades, device scaling along the Moore's Law trajectory has been the major focus of technology innovation in the semiconductor industry. However, this scaling has in recent years slowed down due to power limits, lithography complexity, and other physics limitations. The semiconductor industry has identified several looming technology challenges and expected new design paradigms that demand new "design-based equivalent scaling" approaches to enable continuation of Moore's Law. This thesis addresses several aspects of these challenges, for both the "More-Moore" and "More-than-Moore" domains.Interconnect reliability increases the design uncertainty in advanced node technologies. Electromigration is a growing concern in sub-22nm technology. To close a costly "chicken-egg" loop that spans library characterization and signoff in the presence of design adaptivity, we study the interlock among front-end (device) aging, voltage scaling, and electromigration; we furthermore quantify timing and power costs of meeting lifetime requirements. Based on this, we provide new signoff guidelines and demonstrate that suboptimal choice of voltage step size and scheduling strategy can result in decreased product lifetime.As semiconductor technology advances, leading-edge product companies must rapidly improve yield for designs that seek to reach mass production while still early in the adoption of a new technology node. We study the possible mitigation of yield loss by opportunistic, last-stage redundant logic insertion in early advanced-node production. We describe a yield estimation methodology, and propose an integer linear programming-based optimization of redundant logic insertion for opportunistic yield optimization.In sub-14nm processes, routability challenges arise from multiple patterning and pin access constraints that drastically weaken the correlation between global-route congestion and detailed-routing design rule violations. We present a method that applies machine learning techniques to effectively predict detailed-routing design rule violations after global routing, as well as detailed placement techniques to effectively reduce detailed-routing design rule violations.Beyond conventional design paradigms, three-dimensional integrated circuits (3DICs) with multiple tiers are expected to achieve large benefits (e.g., in terms of power and area) as compared to conventional two-dimensional designs. However, upper bounds on the potential power and area benefits from 3DIC integration with multiple tiers are not well-explored. We use the concept of implementation with infinite dimension to estimate upper bounds on power and area benefits achievable by 3DICs versus 2DICs. We observe that design power sensitivity to implementation with different dimensions correlates well with placement-based Rent parameter of the netlist. We show that the quality of netlist synthesis and optimization benefits from awareness of the target implementation dimension (e.g., 2D versus 3D).Last, aggressive requirements for low power and high performance in VLSI designs have led to increased interest in non-conventional computation paradigms. Approximate and stochastic hardware can achieve improved energy efficiency compared to accurate, traditional hardware modules. To exploit any benefits of approximate and stochastic hardware modules, design tools should be able to quickly and accurately estimate the output quality of composed approximate designs. We propose new accuracy estimation methodologies for approximate hardware and stochastic hardware, respectively. For stochastic circuits, we further investigate opportunities to optimize circuits under aggressive voltage scaling. We find that logical and physical design techniques can be combined to significantly expand the already powerful accuracy-energy tradeoff possibilities of stochastic circuits.


This guide is a resource for students taking SOWK 391. It will lead you to databases with helpful journal articles, books, websites, and other resources.


The chemical industry is one of the industries with the most stringent safety regulations. Regular revision, servicing and maintenance work is required due to the high stress placed on equipment by exposure to very aggressive substances, high temperatures and pressures. This e-fact focuses on the specific risks related to various dangerous substances that maintenance workers in chemical plants are exposed to, and gives some basic recommendations on how these risks can be tackled, including some good practice examples.


This research aims to build a decision support system for real estate bubble early warning in accordance with the forecasted bubble degree. Both theoretical review and empirical evidence will be conducted to determine the ultimate input variables for the forecasting model. It begins with the identification of the symptom indicators of real estate bubble. The quantitative and qualitative information will be analyzed in uncertain and imprecise environments. Then the principal component analysis (PCA) will be applied to categorize these key indicators. Based on the key variables, advanced mathematical methods like artificial neural network (ANN) and support vector machine (SVM) will be deployed for mapping the complicated non-linear relationship between the bubble indicators and the bubble degree. Meanwhile, the forecasting ability of ANN and SVM will be compared, so as to determine a more desirable one for bubble forecasting. Market data from Hong Kong and Mainland China are employed for the empirical study. The ultimate aim is to build a real estate price bubble early warning system (EWS), and provide an objectives basis of planning, decision-making for the government and real estate management departments respectively.


Background In MOBILITY (NCT01061736), SC sarilumab (150 or 200 mg q2w) + MTX demonstrated efficacy in adults with RA and inadequate response to MTX. The most common TEAEs were infections, neutropenia, injection site reactions, and increased transaminases. Objectives To examine association between clinical response and radiographic progression and functional response (HAQ-DI) in MOBILITY. Methods In this post hoc analysis, associations between HAQ-DI and clinical efficacy categories (CDAI, DAS28-CRP, SDAI, and Boolean-based ACR/EULAR remission) were tested at wk 16. Trend for change from baseline (BL) in HAQ-DI across response categories was assessed using the Jonckheere-Terpstra test. Results Regardless of definition, percentage achieving remission (CDAI ≤2.8, DAS28-CRP <2.6, SDAI ≤3.3) or no x-ray progression was higher with sarilumab vs Pbo (P<0.05). Overall, there was a significant trend between magnitude of clinical response at wk 16 and improvement in physical function (Table). This trend was also observed for radiographic progression (mTSS change from BL), regardless of cutoff (≤0.5 and ≤0). In patients achieving remission, there was a numerically greater improvement in HAQ-DI with sarilumab vs placebo (Pbo). Even if patients did not achieve remission or LDA, the sarilumab group had generally greater numerical improvements in HAQ-DI vs Pbo. Conclusions Achieving LDA or remission, or absence of radiographic progression, was associated with overall greater improvement in physical function. Irrespective of whether patients achieved remission or LDA, sarilumab + MTX showed greater improvements in HAQ-DI than Pbo + MTX. Acknowledgements This study was sponsored by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc. Editorial support was provided by MedThink SciCom and funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc. Disclosure of Interest M. Genovese Grant/research support from: Roche, Sanofi, GlaxoSmithKline, R-Pharma, RuiYi, and Bristol-Myers Squibb, Consultant for: Roche, Sanofi, GlaxoSmithKline, R-Pharma, RuiYi, and Bristol-Myers Squibb, H. van Hoogstraten Shareholder of: Sanofi Genzyme, Employee of: Sanofi Genzyme, W. Kampman Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, S. Jayawardena Shareholder of: Sanofi Genzyme, Employee of: Sanofi Genzyme, T. Huizinga Consultant for: Sanofi, Roche, and Abblynx.


Animal movement, expressed through home ranges, can offer insights into spatial and habitat requirements. However, home range estimation methods vary, directly impacting conclusions. Recent technological advances in animal tracking (GPS and satellite tags), have enabled new methods for home range estimation, but so far have primarily targeted mammal and avian movement patterns. Most reptile home range studies only make use of two older estimation methods: Minimum Convex Polygons (MCP) and Kernel Density Estimators (KDE), particularly with the Least Squares Cross Validation (LSCV) and reference (href) bandwidth selection algorithms. The unique characteristics of reptile movement patterns (e.g. low movement frequency, long stop-over periods), prompt an investigation into whether newer movement-based methods –such as dynamic Brownian Bridge Movement Models (dBBMMs)– are applicable to Very High Frequency (VHF) radio-telemetry tracking data. To assess home range estimation methods for reptile telemetry data, we simulated animal movement data for three archetypical reptile species: a highly mobile active hunter, an ambush predator with long-distance moves and long-term sheltering periods, and an ambush predator with short-distance moves and short-term sheltering periods. We compared traditionally used home range estimators, MCP and KDE, with dBBMMs, across eight feasible VHF field sampling regimes for reptiles, varying from one data point every four daylight hours, to once per month. Although originally designed for GPS tracking studies, we found that dBBMMs outperformed MCPs and KDE href across all tracking regimes, with only KDE LSCV performing comparably at some higher-frequency sampling regimes. The performance of the LSCV algorithm significantly declined with lower-tracking-frequency regimes, whereas dBBMMs error rates remained more stable. We recommend dBBMMs as a viable alternative to MCP and KDE methods for reptile VHF telemetry data: it works under contemporary tracking protocols and provides more stable estimates, improving comparisons across regimes, individuals and species.


Females are twice as likely as males to develop posttraumatic stress disorder (PTSD), which may be a function of cultural prescriptions of gender, rather than biological sex. Gender-specific appraisals of trauma (i.e., Criterion A2 of PTSD) may increase susceptibility to developing posttraumatic stress in women. Results showed that exposure to accumulated intentionally caused traumas did not differ across sex. Female sex was associated with a 5.2 odds of endorsement of Criterion A2. After controlling for the effects of different types of traumatic event exposure and biological sex, masculine gender-type was negatively associated with endorsement of Criterion A2. Males classified as masculine were underrepresented in the group of participants who endorsed Criterion A2. Thus, masculine components of identity in males may buffer the effects of initial traumatic stress reactions. Implications for DSM-V are discussed.


Supervised machine learning approaches often rely on a "ground truth" label. However, obtaining one label through majority voting ignores the important subjectivity information in tasks such hate speech detection. Existing neural network models principally regard labels as categorical variables, while ignoring the semantic information in diverse label texts. In this paper, we propose AnnoBERT, a first-of-its-kind architecture integrating annotator characteristics and label text with a transformer-based model to detect hate speech, with unique representations based on each annotator's characteristics via Collaborative Topic Regression (CTR) and integrate label text to enrich textual representations. During training, the model associates annotators with their label choices given a piece of text; during evaluation, when label information is not available, the model predicts the aggregated label given by the participating annotators by utilising the learnt association. The proposed approach displayed an advantage in detecting hate speech, especially in the minority class and edge cases with annotator disagreement. Improvement in the overall performance is the largest when the dataset is more label-imbalanced, suggesting its practical value in identifying real-world hate speech, as the volume of hate speech in-the-wild is extremely small on social media, when compared with normal (non-hate) speech. Through ablation studies, we show the relative contributions of annotator embeddings and label text to the model performance, and tested a range of alternative annotator embeddings and label text combinations.


This study examined the development of the public discussion on Twitter about the abusive comments specific to misogynistic discourse after the suicide of Sulli, a female celebrity in South Korea. Both the pattern of social networking between the users and the semantic representations of user responses were analyzed from a social network perspective using a large-scale Twitter dataset. A total of 37,101 tweets generated by 25,258 users were collected and analyzed. The findings of the network analysis suggest that hubs and authorities on Twitter were closely connected to each other and contributed to promoting the public discussion about abusive comments in response to her death. The results of the semantic network analysis suggested that her death, presumably due in part to continuous hateful comments from trolls, evoked an open discussion about the deeply rooted abusive comments and misogyny that are prevalent in South Korea. Users perceived that sensational news coverage about celebrities and unethical journalistic practices led to abusive comments and her death. The users shared their observations that gendered hate speech contributed to Sulli's bullying. Dominant words that referred to Sulli's sexual harassment show the ways in which haters had bullied her, as well as the criticism of online harassment. The results imply that the issue of online misogyny was closely associated with abusive comments in the public consciousness. This study verified the role of celebrities in increasing awareness about social issues and word-of-mouth dissemination even after a death. This study also offers methodological insights by demonstrating how social network analysis can be used to analyze public discussion using big data.


A newborn female with intrauterine growth retardation, bilateral cleft lip and palate, absent external nares and eyelids, low set ears, short contracted limbs, webbed digits, intestinal malrotation, and unilateral renal agenesis is reported. These multiple malformations are considered part of the Neu-Laxova syndrome.


In this paper, we describe a design method and experimental results of a newly developed MR Fluid clutch which has a multi-layered disks and micro-size (50 micro meters) gaps of MR Fluid. The micro-size gap works for the reduction of magnetic resistance, amount of power supply and size of the total system. Static torques of the device was predictable with conventional magnetostatic analyses. Additionally, dynamic test shows that its response time is about 20 milliseconds.


This paper analyses the transition from a hunter-gat herer economy to another one based on agriculture and animal-husbandry in the eastern part of the Iberian Penin sula. Based on a comparative study of epipaleolithic and ear/y neolithic sites with radiocarbon dates ami/ or studies of fauna or cereals finds, we propose three models to explain the archaeological record.


Background: Patients with sepsis-associated acute kidney injury (AKI) are at risk of kidney damage, potentially necessitating acute temporary or chronic dialysis. Our study aims to estimate the odds ratio (OR) of preceding sepsis among patients requiring their first dialysis. Methods: A nationwide population-based case-only study was conducted using claims records from the National Health insurance database of Taiwan. All patients over 20 years of age who underwent their first dialysis between 2004 and 2016 were included in the study. The six months prior to their first dialysis served as a self-control period. Results: The study included 147,201 patients who required acute temporary and 75,031 patients who required chronic dialysis. The odds ratios for patients needing acute temporary dialysis after 1, 2, 3, and 4 weeks of exposure periods were 15.8, 10.7, 9.2, and 8.4, respectively. The ORs for patients requiring chronic dialysis were 7.0, 4.1, 4.2, and 3.7, respectively. Conclusions: Our findings indicate that sepsis was substantially associated with an increased risk of renal failure. The risk was highest during the first week following sepsis for both acute temporary and chronic dialysis cases.


Inclusive and sustainable industrial development implies environmental friendly industrial growth with positive implications for social targets such as employment generation. One of the most important options available to policymakers for reducing CO 2 emissions is industrial energy efficiency, which is particularly relevant for the discussion on green industrialization. Despite this intuitive concept, the economics measurement toolkit still lacks a methodological framework to analyse the extent to which energy efficiency interventions can generate simultaneous economic, environmental and employment-related improvements to boost inclusive and sustainable industrial development. This study fills this gap by introducing an original approach based on input-output tables to estimate the impact of improvements in industrial energy efficiency on value added, employment and energy savings among industries in the Republic of North Macedonia. The results show that triple dividends are possible in terms of inclusive and sustainable industrial development. Whereas a positive impact on employment is found in every scenario, a positive outcome in terms of value added essentially depends on the country's capacity to produce goods that accommodate firms' increasing demand from their use of energy cost savings.


Metarhizium robertsii is a plant root colonizing fungus that is also an insect pathogen. Its entomopathogenicity is a characteristic that was acquired during evolution from a plant endophyte ancestor. This transition provides a novel perspective on how new functional mechanisms important for host switching and virulence have evolved. From a random T-DNA insertion library, we obtained a pathogenicity defective mutant that resulted from the disruption of a sterol carrier gene (Mr-npc2a). Phylogenetic analysis revealed that Metarhizium acquired Mr-npc2a from an insect by horizontal gene transfer (HGT). Mr-NPC2a binds to cholesterol, an animal sterol, rather than the fungal sterol ergosterol, indicating it retains the specificity of insect NPC2 proteins. Mr-NPC2a is an intracellular protein and is exclusively expressed in the hemolymph of living insects. The disruption of Mr-npc2a reduced the amount of sterol in cell membranes of the yeast-like hyphal bodies that facilitate dispersal in the host body. These were consequently more susceptible to insect immune responses than the wild type. Transgenic expression of Mr-NPC2a increased the virulence of Beauveria bassiana, an endophytic insect-pathogenic fungus that lacks a Mr-NPC2a homolog.


Background Early intervention with an effective disease-modifying drug (DMD) offers the best chance of limiting the inflammatory process that contributes to irreversible axonal damage correlating with disability in multiple sclerosis (MS). It is equally important to ascertain fairly quickly whether patients are responding positively to the choice of therapy to allow time for either a treatment modification or a switch in treatment, a process we termed "treatment optimization". Various treatment optimization recommendations (TOR) have been proposed to help decide when a patient taking an MS DMD might be showing a sub-optimal response. We have applied the clinical scheme proposed by the Canadian TOR to the patients involved in the Prevention of Relapses and disability by Interferon Subcutaneously in MS 4-year (PRISMS-4) study, who received interferon β-1a treatment for 4 years, with the TOR applied retrospectively at year 1. Objective The aim of this investigation was to examine whether these TOR were able to predict which patients would go on to develop disease breakthrough (defined as any relapses or disease progression), indicative of a sub-optimal response over the ensuing 3 years of study and therefore might have benefited from a change in treatment. Results We found 39% of patients receiving therapy experienced either a medium or high level of concern of breakthrough after a year of treatment, and 89% of these patients went on to develop further breakthrough over years 2–4. Although 67% of the 61% of patients having no or low-level concern after a year of treatment also experienced further disease breakthrough, it was significantly less than the medium or high group. Conclusion This study shows that the Canadian TOR may be an important tool for early treatment optimization.