It is well known that fever often occurs in patients with congestive heart failure. During the early use of the clinical thermometer Wunderlich 1 noted this finding, but he also said that subnormal temperatures were by no means uncommon. In reviewing the medical literature it is surprising to find so little has been said either about fever in relation to congestive heart failure or concerning the frequency with which complications occur in patients suffering from that disease. Harrison's 2 opinion, as expressed in his book entitled "Failure of the Circulation," is as follows: Fever in some degree occurs in a large proportion of patients with congestive heart failure. A slight increase in temperature may possibly be dependent on the increase in the metabolic rate which many patients exhibit, but fever of more considerable magnitude usually signifies infection, infarction, or thrombus formation. More commonly fever is to be ascribed to pulmonary


Today is nothing similar to yesterday, at our time.In this respect, when we examine especially advertising sector, we see that there are some forces shaping our world and these forces are very different from the forces in the past. We also witness rapid changes occuring in a day within minutes. In this respect, the condition of advertising sector in Turkey is similar to that in other countries. When we examine political advertising campaigns held in Turkey and the researches made about them, we see that the necessary archiving has not been done and this subject has not been dealt with according the political science so far. We encounter with "Advertising" that has an increasingly popularity when we analyse some concepts on political promotion amd marketing recently. As a consequence, the changes in the world conjuncture and differing position of political promotion shaped this work and brought it to the agenda. According to the mentioned determiners, of a different research subject from the previous ones is diffened due to different approach on communicvation science and corresponding promotion discipline. Beside, the concept of this work is determined according to; political promotion, perception abd practices in Turkey, promotion from the perspectives of Turkish politicians, the political panaroma of Tırkey and the analysis of historical development of political promotion. Regarding the table resulting from the general evaluation, the limits of research are completed with the evaluation of the political promotion campaigns done in pre-elections in Turkey between 19502002, the changes and effescts of slogan, target mass and vote preferences and the evaluation of their effects in quality and quantity.


Transmission and scattering problems involving complex potentials are important in physics, in particular in describing nuclear collisions. We describe many pedagogical features of transmission in one dimension and scattering and absorption cross sections in three dimensions for a rectangular absorptive potential and compare the results with scattering from real barriers and a hard sphere. For a given energy in one dimension we show that the absorption reaches a maximum for a critical value of the absorption strength and then monotonically decreases with an increase in the absorption strength. An infinitely absorptive well becomes almost fully reflective and thus is similar to an infinitely high barrier. Similar results are found in three dimensions. We show that the absorption cross section in three dimensions diverges at a threshold energy, which is of critical importance for exothermic reactions.


One of the major causes of premature failure in asphalt pavements is moisture damage. Asphalt mixtures designed without considering climate impacts may suffer from durability problems caused by movement of water inside the asphalt mixture. Rolling traffic over wet pavement builds up pore pressure in the mixture, which will consequently accelerate deterioration. The objective of the study was to assess the moisture damage to asphalt concrete mixtures by means of complex modulus testing of dry and moisture-conditioned asphalt specimens with various mixture compositions. The asphalt mixtures were conditioned with the Moisture Induced Sensitivity Tester (MIST), which aims to replicate pore pressure in field conditions. The results showed a decline in stiffness modulus and a reduction in elastic properties after MIST conditioning. In addition, the results indicated that binder content and air void content had a significant influence on the reduction in stiffness. To capture the relationship between air void content, binder content, and the reduction in stiffness, a relationship was developed and validated with measurements on cores extracted in the field.


Point-of-care ultrasound is often used as first line imaging for the evaluation of flank pain in the emergency department and can potentially expedite diagnosis or decrease the use of abdominal CT scans, preventing unnecessary radiation exposure. This is a case report of a 77-year-old female who presented with acute flank pain. Point-of-care ultrasound revealed the absence of a ureteral jet on the right side, supporting the diagnosis of ureteral obstruction, which was confirmed on computed tomography. This case report aims to demonstrate the value of identification of ureteral jets when using point-of-care ultrasound to diagnose ureteral obstruction. Knowledge of more subtle and specific ultrasound findings such as this can help expedite more precise diagnoses. Topics Ureteral obstruction, ureteral jets, hydronephrosis, renal colic, renal calculi, point-of-care ultrasound, flank pain.


Decision theory has become widely accepted in the AI community as a useful framework for planning and decision making. Applying the framework typically requires elicitation of some form of probability and utility information. While much work in AI has focused on providing representations and tools for elicitation of probabilities, relatively little work has addressed the elicitation of utility models. This imbalance is not particularly justified considering that probability models are relatively stable across problem instances, while utility models may be different for each instance. Spending large amounts of time on elicitation can be undesirable for interactive systems used in low-stakes decision making and in time-critical decision making. In this paper we investigate the issues of reasoning with incomplete utility models. We identify patterns of problem instances where plans can be proved to be suboptimal if the (unknown) utility function satisfies certain conditions. We present an approach to planning and decision making that performs the utility elicitation incrementally and in a way that is informed by the domain model.


Lymph nodes are organs that control immune cells and provide a major pathway for primary tumors to metastasize. A nanoparticles-based strategy has several advantages that make it suitable for achieving effective lymphatic delivery. First, the size of nanoparticles can be tailored to meet a size range appropriate for lymphatic migration. In addition, functionalized nanoparticles can target cells of interest for delivery of drugs or imaging probes. Existing lymph node contrast agents map all lymph nodes regardless of metastasis status; however, by using nanoparticles, it is possible to selectively target lymphatic metastases. Moreover, using functionalized nanoparticles, it is possible to specifically deliver anticancer drugs to metastatic lymph nodes. In this review, we introduce the use of nanoparticles for lymphatic mapping, in particular highlighting design considerations for detecting metastatic lymph nodes. Furthermore, we assess trends in lymph node-targeting nanoparticles in clinical practice and suggest future directions for lymph node-targeting nanoparticles.


An endeavor is made to outline the history of that phase of the conservation movement which has led to unit operation since the World War period; also to show that the geologist has played a vital part in furthering its cause and in bringing the petroleum industry to an appreciation of the advantages of developing an oil and gas structure as a geological unit. A summary is given of the geology of six oil and gas fields involving public lands in the western United States now under unit operation, namely, North and Middle domes of Kettleman Hills, California, Little Buffalo Basin, Big Sand Draw, Billy Creek, and Pitchfork fields in Wyoming. The geology of the McCallum field, North Park, Colorado, for which unit operation is contemplated, is also reviewed. The Federal laws and regulations governing unit operation on lands in which mineral title is still in the Government are cited and the salient geological and administrative features to be considered in the presentation of plans for unit operation of cooperative development for approval by the Secretary of the Interior are suggested.


Skin is a comparatively accessible organ possessing many conserved regulatory and signaling pathways, drawing researchers from varied fields toward its study. Hair follicle (HF) biology in particular has expanded rapidly over the preceding decade, helping to shape and develop scientific knowledge across diverse areas of biomedical research, beyond the skin. The hope in compiling this review is to inspire more researchers to utilize the HF as an instructive biological model, bringing with them fresh perspectives and experience from differing fields of study. The authors also wish to further motivate seasoned hair researchers to explore the further reaches of their understanding and the discoveries yet to be made. For this reason, the authors have endeavored to collate an eclectic mix of some of the most thought‐provoking and scientifically intriguing articles associated with the field of HF research, published in the preceding two years.


Incentives of executives and board of directors play an important role in corporate decisions. Principal agent theory suggests a tradeoff between risk and incentives in optimal compensation contracts for managers. The first essay of this dissertation explores the relationship between the distribution of incentive compensation among top executives and firm risk. This essay develops and tests a two-agent model of optimal incentive compensation for corporate executives. The model investigates the effects of firm risk and cooperation among executives in the design of incentive contracts and offers two contrasting propositions: 1. When importance of cooperation is invariant to risk, the ratio of incentive compensation of the CEO to that of other top executive(s) increases with risk. 2. In contrast, when importance of co-operation increases with risk, the ratio of incentive compensation first increases and then decreases with risk. Using EXECUCOMP data from 1992 to 2002 I test these propositions and find evidence supporting the second proposition, but none for the first.The second essay examines the relation between board independence of target firms and the returns to targets and acquirers around takeover announcements. Using a sample of 232 large relative size takeovers, I reexamine whether target board independence is related to target or acquirer returns and their share in the total wealth change around announcements. Unlike Cotter et al. (1997), I do not find independent target boards to be associated with higher target premiums or lower acquirer returns. Similar to Wulf (2004), I find that target returns are lower when target CEOs obtain CEO positions in the merged firm. However, target board independence does not mitigate the lower premium targets receive when their CEOs are CEOs of the merged firm. I conclude that the takeover market is competitive such that target board independence is unrelated to gain sharing between targets and acquirers in larger relative size takeovers.


BACKGROUND
The aim of this study was to confirm our clinical impression that intra-abdominal handlebar injuries are progressively increasing in number and severity in the latest years.

METHODS
A retrospective analysis of data concerning 132 patients admitted to our department of pediatric surgery during a 10-year period (between 2003 and 2012), following bicycle-related blunt abdominal trauma, was performed. Patients were divided into two groups: those who fall from their bicycle (N.=43) and those who sustained direct impact from the handlebars (N.=89) and compared.

RESULTS
Number of admitted patients due to bike related injury was increased during a 10-year period. The bikes used by 91.6% of the participants were the high quality BMX, with rigid and strong handlebars. The average age for both groups was 10.3 years (4-16 years). Boys were injured more than girls. Thirty patients from both groups sustained severe abdominal visceral injuries, 25 from the handlebar group and 6 from the fall group (P=0.018). The overall average length of hospital stay was 3.04 days, with 36 cases (27.36%) requiring pediatric intensive care unit (PICU) admission (N.=26 of the handlebar group and N.=10 of the fall group, P=0.024). Eight children sustaining handlebar injuries required abdominal surgery compared to only one case for the fall group (P=0.018), when excluding extra-abdominal procedures.

CONCLUSIONS
Number of pediatric patients admitted due to bike related injury has been gradually increasing. Children who suffer from direct impact of the handlebars are more likely to require abdominal operative intervention and PICU admission than those who fall. Preventive measures are urgently needed in order to defeat this trend.


Abstract Hydrothermal systems associated with oceanic spreading centres are now recognized as relatively common phenomena, and the organic chemistry occurring there is geologically rapid and novel. Especially in the marine hydrothermal systems at water depths >1.5 km, this chemistry proceeds at high temperatures (up to >400° C) and high pressures (>150 bar) in an aqueous open flow medium. Continental systems may also be of interest, as for example failed or dormant rifts and regions around piercement volcanoes. Organic matter alteration to petroleum hydrocarbons by reductive reactions occurs in hydrothermal systems over a wide temperature window (c. 60 to >400° C), under high pressure, and in a brief geological period of time (years to hundreds of years). Thus, the products are considered to be in a metastable equilibrium state during their brief formation and residence times at high temperatures. These conditions are conducive to organic chemistry which yields concurrent products by reduction (due to mineral buffering), oxidation (high thermal stress) and synthesis. Therefore, this brief time interval coupled with the wide range of hydrothermal petroleum compositions indicates that organic matter maturation and petroleum generation, expulsion and migration occur as an overlapping continuous process during hydrothermal activity. The behavior of organic matter (CH4-C40+) in near to supercritical water, in many cases with associated high concentrations of CO2 and methane, needs to be further characterized in order to understand the implications of this novel phenomenon in geological and geochemical processes.


By now, most companies know that activity-based costing, an innovative accounting system that breaks down overhead far more precisely than old-fashioned systems do, can be used to trim waste, improve service, and make better product-mix and pricing decisions. Yet the actual design and implementation of a successful ABC system remains largely a mystery for many companies. Analyzes the experiences of eight real-life companies who took on the challenge of implementing an ABC system, revealing the mistakes, successes, and ultimate triumphs that resulted in each case. Winner of the Notable Contribution to Management Accounting Literature Award.


: Compassion unites people during times of suffering and distress. Unfortunately, compassion cannot take away suffering. Why then, is compassion important for people who suffer? Nurses work in a domain where human suffering is evidently present. In order to give meaning to compassion in the domain of professional care, it is necessary to describe what compassion is. The purpose of this paper is to explore questions and contradictions in the debate on compassion related to nursing care. The paper reviews classical philosophers as well as contemporary scientists' main arguments on compassion. First, I will examine the relationship between compassion and suffering. Second, how does one recognize serious suffering? This issue raises questions about the role of imagination and the need for identification. Third, literature describes compassion as an emotion. Some philosophers consider emotions uncontrollable feelings; others see a clear rational dimension in emotions. In order to determine what compassion is, it is necessary to weigh these contradictional arguments. Fourth, I will discuss motives for compassion. Is compassion an act of altruism or egoism? In this debate Nietzsche and Schopenhauer are well-known opponents. Today, analysis of their arguments leads to some surprising conclusions. Fifth, there is the issue of fault and compassion. Can we only feel compassionate when people who suffer are not to blame for their own suffering? Such a condition faces professional caretakers with a dilemma which needs a thorough analysis if compassion is to be of use in the field of professional care. Finally, I will explore the moral meaning of compassion. Compassion, described as a concept with cognitive as well as affective dimensions, also has volitional and behavioural aspects. These aspects specifically are of importance to nursing care and further research of compassion in the nursing domain.


Objective To examine the costs and cost effectiveness of telehealth in addition to standard support and treatment, compared with standard support and treatment. Design Economic evaluation nested in a pragmatic, cluster randomised controlled trial. Setting Community based telehealth intervention in three local authority areas in England. Participants 3230 people with a long term condition (heart failure, chronic obstructive pulmonary disease, or diabetes) were recruited into the Whole Systems Demonstrator telehealth trial between May 2008 and December 2009. Of participants taking part in the Whole Systems Demonstrator telehealth questionnaire study examining acceptability, effectiveness, and cost effectiveness, 845 were randomised to telehealth and 728 to usual care. Interventions Intervention participants received a package of telehealth equipment and monitoring services for 12 months, in addition to the standard health and social care services available in their area. Controls received usual health and social care. Main outcome measure Primary outcome for the cost effectiveness analysis was incremental cost per quality adjusted life year (QALY) gained. Results We undertook net benefit analyses of costs and outcomes for 965 patients (534 receiving telehealth; 431 usual care). The adjusted mean difference in QALY gain between groups at 12 months was 0.012. Total health and social care costs (including direct costs of the intervention) for the three months before 12 month interview were £1390 (€1610; $2150) and £1596 for the usual care and telehealth groups, respectively. Cost effectiveness acceptability curves were generated to examine decision uncertainty in the analysis surrounding the value of the cost effectiveness threshold. The incremental cost per QALY of telehealth when added to usual care was £92 000. With this amount, the probability of cost effectiveness was low (11% at willingness to pay threshold of £30 000; >50% only if the threshold exceeded about £90 000). In sensitivity analyses, telehealth costs remained slightly (non-significantly) higher than usual care costs, even after assuming that equipment prices fell by 80% or telehealth services operated at maximum capacity. However, the most optimistic scenario (combining reduced equipment prices with maximum operating capacity) eliminated this group difference (cost effectiveness ratio £12 000 per QALY). Conclusions The QALY gain by patients using telehealth in addition to usual care was similar to that by patients receiving usual care only, and total costs associated with the telehealth intervention were higher. Telehealth does not seem to be a cost effective addition to standard support and treatment. Trial registration ISRCTN43002091.


Metaphor has proven to be one of the richest and most robust ideas in the design of computer applications and user interfaces. The basic idea is very simple: present functionality in such a way that the user can access and apply specific prior knowledge while learning and using a novel tool. But the practical and theoretical ramifications of this idea both in the brief history of humancomputer interaction and in its current prospects are quite considerable. In this paper, we first summarize a view of the relevant history. We then develop the notion that metaphors should be conceived of as bound to contexts of use: The recognition and interpretation of metaphors typically depends upon the establishment of a meaningful task context. We think there is a need to focus consideration of metaphors on the scenarios of use from which they arise. We suggest that this reconception of metaphors as bound to scenarios of use converges with recent developments in scenario-based specification and object-oriented design, and that it provides new opportunities for putting metaphors to work in the specification, design and implementation of systems.


Objective. Dynamic, contrast-enhanced magnetic resonance imaging (DCE-MRI), the quantification of enhancement within the synovial membrane and bone by extracting curves using fast T1-weighted sequences during intravenous administration of contrast agent, evaluates synovitis and bone marrow edema in psoriatic arthritis (PsA). In this pilot study, we looked at possible differences between joint synovitis and tenosynovitis in PsA as compared with rheumatoid arthritis (RA). Methods. Seven patients with PsA and 10 with RA were studied. After DCE-MRI was performed on 3 axial slices of the wrist, the enhancement ratio was calculated on 6 different regions of interest (ROI) of the synovial membrane outlined by the operator: the wrist compartment, 3 extensor tendon compartments, and 2 flexor compartments. DCE-MRI results were quantitatively analyzed using the Dynamika software, a computer-aided semiautomated method. Results. In PsA, the area of the ROI outlined around the first and second extensor compartments was larger than in RA; the opposite was true for the extensor carpi ulnaris region. The volume of inflammation was significantly higher in RA than in PsA for all the extensor compartments except the second, and in the joint synovial membrane. The DCE-MRI indicators of the degree of inflammation were higher for PsA in the joint synovial membrane (p = 0.002 and p < 0.001, respectively). There was a significant correlation between volume of inflammation but not its degree and 28-joint Disease Activity Score at the level of the wrist joint (r = 0.6; p = 0.01). Conclusion. DCE-MRI can reveal useful and potentially clinically important information on the characteristics of different types of arthritis.


The deep inferior epigastric perforator (DIEP) flap is used with increasing frequency in post-mastectomy breast reconstruction. Preoperative mapping with CT angiography (CTa) is crucial in reducing surgical complications and optimizing surgical techniques. Our study's goal was to investigate the accuracy of conventional CT (cCT), performed during disease staging, compared to CTa in preoperative DIEP flap planning. In this retrospective, single-center study, we enrolled patients scheduled for mastectomy and DIEP flap breast reconstruction, subjected to cCT within 24 months after CTa. We included 35 patients in the study. cCT accuracy was 95% (CI 0.80–0.98) in assessing the three largest perforators, 100% (CI 0.89–100) in assessing the dominant perforator, 93% (CI 0.71–0.94) in assessing the perforator intramuscular course, and 90.6% (CI 0.79–0.98) in assessing superficial venous communications. Superficial inferior epigastric artery (SIEA) caliber was recognized in 90% of cases (CI 0.84–0.99), with an excellent assessment of superficial inferior epigastric vein (SIEV) integrity (96% of cases, CI 0.84–0.99), and a lower accuracy in the evaluation of deep inferior epigastric artery (DIEA) branching type (85% of cases, CI 0.69–0.93). The mean X-ray dose spared would have been 788 ± 255 mGy/cm. Our study shows that cCT is as accurate as CTa in DIEP flap surgery planning.


Introduction The reported incidence of JE among patients with acute encephalitic syndrome (AES) in Nepal ranges between 20% to 62%. In light of the lack of up-to-date data, we sought to describe the epidemiology of JE in Chitwan, Nepal. Methods A prospective observational study was conducted during 2010–2012 in the College of Medical Science in the Chitwan District. Patients with suspected JE were tested for anti-JE IgM in serum and cerebrospinal fluid (CSF). Results Of 227 all patients tested, 18 (7.9%) were found positive for JE. 17/202 (8.4%) patients with AES had JE. All, with the exception of two patients, were diagnosed on the basis of positive a serologic test, both in serum and CSF samples. Patients with JE were significantly older (42.1±27.6 years) than patients without JE (25.6±25.2 years, p = 0.02). Half of JE cases occurred in adults older than 50. More of the JE cases (11/18, 61.1%) occurred during the rainy season when compared to the JE negative patients [71/209, (34%), p = 0.01]. None of the JE patients had a relevant travel history, and one recalled having been immunized against JE. There was a variation in the geographic distribution of cases across the districts of the central Terai. Conclusions In this cohort, the proportion of patients with AES who had JE was lower than in previous studies. In addition, most patients were adults, and cases were not distributed uniformly across the central Terai region. The risk of acquiring JE by short-term travelers in the area is likely to be low. Vector-control programs and the promotion of mosquito avoidance behavior in the Terai region should continue. The high proportions of adults among patients with JE may suggest recent changes in the epidemiology of JE in the central Terai region, and routine immunization of all adults should be considered.


The article proposes a methodology for assessing the development of damage in building structures, subjected to differential settlement and uplift, using the analysis of Interferometry Synthetic Aperture Radar (InSAR) data. The proposed methodology is targeted towards general applicability, capable of providing assessment results for measurements over wide geographic areas and for varying structural typologies. The methodology is not limited to ground movement measurements linked to tunnelling, as is the common case. Instead it extends to the monitoring of arbitrary movement in buildings, for example, due to ground consolidation, water table changes or excavation. The methodology is designed for use alongside patrimonial building databases, from which data on individual building geometry and typology are extracted on a region or country scale. Ground movement monitoring data are used for the calculation of the building deformation, expressed in different types of deformation parameters. The combined use of this data with analytical models for settlement damage classification in building structures enables the assessment in patrimonial building structures, at a country scale. The methodology is elaborated and applied on the patrimonial inventory of Belgium for the evaluation of potential settlement and uplift damage on buildings over a period of nearly three decades. The analysis results are compared to on-site observations.


INTRODUCTION
Intrathyroid metastases are uncommon. Clinically, the distinction may be difficult with thyroid malignant tumor.

CASE REPORT
A 76-year-old woman was referred to our department for an evaluation of a dysphonia. She had a past history of renal cancer 6 months ago. A multinodular goiter was noticed at the palpation. Left recurrent laryngeal nerve palsy was observed; there was no cervical lymph node. Fine-needle aspiration was not contributive. Computed tomography confirmed the multinodular goiter. Total thyroidectomy was performed and final histologic examination revealed a metastasis of a renal cancer.

CONCLUSION
Even if intrathyroid metastasis are rare, the practitioner must suggest the diagnosis if the patient had a thyroid tumor and a past history of cancer. A fine-needle aspiration can help the diagnosis. The surgical management is recommended for isolated metastasis to the thyroid gland especially in renal cancer.


Multidrug drug-resistant (MDR)-Acinetobacter baumannii (A. baumannii) is one of the most feared nosocomial bacterial agents worldwide, and the World Health Organization classified carbapenem-resistant strains as a priority "1" critical pathogen. In Nigeria, the paucity of information on this pathogen makes it difficult to estimate its potential impact on public health and veterinary medicine. This systemic review was done to prepare an impact assessment for One Health based on the occurrence of A. baumannii in different environments and the antimicrobial resistance. A detailed search of articles on A. baumannii in Nigeria was conducted using search strings in the following databases: PubMed, Scopus, Google search engine, and Google scholars. This study revealed that 14 out of the 36 states in Nigeria reported A. baumannii. Specifically, 19/24 articles described isolates from clinical settings, 4/24 from the environment, and 1/24 from animal sources. A. baumannii occurrence of 9.15% (503/5496) was recorded from 8.4% (418/4950), 16.06% (80/498), and 10.42% (5/48) of samples of clinical, environmental, and animal origin by culture, respectively. The most common antibiotics to which A. baumannii was resistant were chloramphenicol, ampicillin-sulbactam, amoxicillin, amoxicillin-clavulanate, cefuroxime, ceftazidime, ceftriaxone, gentamycin, and tetracycline. Seventeen resistance determinants were described for A. baumannii isolates originating mostly from clinical sources with blaOXA-51 and blaOXA-23 gene makers frequently reported. This study demonstrates the lack of data on A. baumannii from animals. Clinical MDR- A. baumannii isolates, particularly in Intensive Care Units (ICUs), are a severe public health concern in Nigeria. Thus, findings from this review will form a baseline for future surveillance research.


Three anti-cholecystokinin antibodies were used to label the stomatogastric nervous system of the crab Cancer borealis. Labeled tissues were examined as whole mounts using laser scanning confocal microscopy. Although each of the anti-cholecystokinin antibodies labeled a variety of structures within the stomatogastric nervous system (including somata, fibers and neuropil), the pattern of labeling produced by each antibody was distinct. These results indicate that there is a family of cholecystokinin-like molecules that are differentially distributed among a subpopulation of the neurons in the stomatogastric nervous system of Cancer borealis.


Objective.To examine the distribution of risk and the correlation between risks in a home care population with regard to several important adverse outcomes. Background.Researchers and policy makers have long recognized the heterogeneity of home care populations. Most research in this area focuses on identifying predictors of adverse outcomes. The degree of the heterogeneity of risks is much more poorly understood. Yet understanding the degree of risk heterogeneity at the population level is important because it has implications for the extent to which the level of care should vary among recipients. Study setting. Patients enrolled in the Arizona Health Care Cost Containment System (AHCCCS) program, between the December 1992 and April 1998. Outcome measures. Estimating the risk for nursing home placement, hospitalization, death, and functional decline. Methods.Estimating discrete time hazard models. From these models the predicted risk for each outcome is estimated and the distribution and correlation of predicted risks is examined. Model fit is assessed through split sample techniques and by examining the ratio of predicted to actual outcomes for selected sub-groups. Results.The estimates reveal a wide variation in predicted risk. The ratio of predicted risk at the 90th percentile relative to the 10th percentile ranges from 4.99 for nursing home admission to 6.65 for hospitalization. The distributions of predicted risks are all skewed, particularly the distributions for death and nursing home admission. Predicted nursing home risk is highly correlated with the predicted risk for death (&rgr; = 0.71). The predicted risk for hospitalization is not strongly correlated with the predicted risk for either death or nursing home admission. Conclusion.The wide variation in risk among home care patients suggests that efficient allocation of resources would require variation in spending and targeting of services based on patient characteristics. Greater research regarding the effectiveness of home care for different sub-populations is called for.


In the Paleoproterozoic Transamazonas Province, synkinematic granitogenesis has taken place synchronously with compressive tectonic stress. The synkinematic character of the granites is marked by their WNW elongate shape, and by the presence of pervasive and concordant synmagmatic foliation. Ductile shear zones are concordant to the previous regional WNW structures, and tend to be accommodated along contacts between Rhyacian synkinematic granitoids and both Archean orthogneisses and Siderian metabasites. Locally phyllonitic shear zones and brittle-ductile shear zones with cataclasites are oriented subparallel to the preexisting ductile foliation. Late orogenic brittle faults N30E-trending strike-slip faults are either sinistral or destral. 40Ar/39Ar dating of muscovite developed on fault planes gave ages of 1977 ± 8 Ma and 1968 ± 11 Ma. Structural and geochronological data from rocks of the Transamazonas Province permit to conclude that most mylonites and brittle structures were controlled by preexisting structures such as geological contacts and petrographic facies boundaries. Compressive tectonic stress would have initiated at ca. 2100 Ma, since the former magmatic arc (Bacajai complex), still present at 2070 Ma when syntectonic granites were emplaced and remained until 1975 Ma after granite plutonism and regional cooling.


Agriculture is one of the key drivers of Ethiopia's long-term development and food security. It supports 85% of the total population, constitutes 43% of GDP and 80% of export value. For the country to reach middle-income prestige by 2025 and make significant inroads against food insecurity, strategic choices and concerted and strategic investments in agricultural sector are vigorous. The government of Ethiopia has put maximum efforts to increase agricultural output. However, increments in agricultural production and productivity, the expected benefits, have not been achieved yet. Low agricultural production and productivity is the major cause of food insecurity in the country emanating from lack of suitable technologies for beneficiaries, low adoption of agricultural innovations, and lack of active participation of farmers in agricultural research. Therefore, this study examines critical factors that hinder farmers' participation in agricultural research in Ethiopia. A total sample size of 39 respondents comprising 16 farmers, 14 researchers and 9 development agents were interviewed purposively based on snowball sampling technique. Qualitative research design was used in this research. Data were collected using semi-structured interviews, focus group discussions and observations and analysed descriptively. The empirical results reveal that lack of sufficient time, bad experiences in the past, perception of farmers' for researchers, farmer's attitude for research, the type of research, lack of stakeholder's willingness to learn from one another, loose integration of indigenous and scientific knowledge and insignificant change of new technologies to material wealth critically hindered farmer's participation in agricultural research to bring innovation in agriculture. Innovation in agriculture comes from the interaction of the different actors that are working in agriculture since each actor brings their own knowledge and results in social learning. Insignificant innovation in agricultural research results in food insecurity in the country.


The utility of R-2(2)(9) biimidazole-carboxylate, R-2(2)(10) biimidazole-oxalate/squarate and R-2(2) (9) biimidazole-(tris-oxalate) synthons is considered for crystal engineering of hydrogen-bonded networks based on [Co-III(H(2)biim)(3)](3+) cations (H(2)biim = 2,2-biimidazole) and oxalate, squarate or [M-III(C2O4)(3-) anions. Syntheses and crystal structures are described for [Co-III(H(2)biim)(3)](3-) [M-III(C2O4)(3)]center dot 2H(2)O (M = Cr, 1; M = Co, 2), [Co-III(H(2)biim)(3)](HC4O4)(3)center dot 2H(2)O, 3, and [Co-III(H(2)biim)(3)](C2O4)Cl center dot 5.5H(2)O, 4. Compounds 1 and 2 are isostructural and comprise [Co(H(2)biim)(3)](3+) cations bridged by [M(oxalate)(3)](3-) anions in two directions and water molecules in the third direction to give a 3D H-bonded network. Both outer and inner 0 atoms of the coordinated oxalate ions act as H-bond acceptors, forming motifs closely related to the anticipated R-2(2)(9) biimidazole-(tris-oxalate) synthon. Compound 3 contains a more complex H-bond pattern in 3D, built from the intended R-2(2)(10) biimidazole-squarate synthon and additional H-bonds between protonated squarate molecules and water molecules. The structure of compound 4 (obtained with synchrotron radiation) contains layers in which stacked pairs of oxalate anions bridge between [Co-III(H(2)biim)(3)](3+) cations to form a dense 2D kgd-net, separated by layers of disordered chloride anions and H-bonded water molecules.


The source responsible for reionizing the universe at z>6 remains uncertain. While an energetically adequate population of star-forming galaxies may be in place, it is unknown whether a large enough fraction of their ionizing radiation can escape into the intergalactic medium. Attempts to measure this escape fraction in intensely star-forming galaxies at lower redshifts have largely yielded upper limits. In this paper, we present new Hubble Space Telescope Cosmic Origins Spectrograph and archival Far-Ultraviolet Spectroscopic Explorer (FUSE) far-UV spectroscopy of a sample of 11 Lyman Break Analogs (LBAs), a rare population of local galaxies that strongly resemble the high-z Lyman Break galaxies. We combine these data with Sloan Digital Sky Survey optical spectra and Spitzer photometry. We also analyze archival FUSE observations of 15 typical UV-bright local starbursts. We find evidence of small covering factors for optically thick neutral gas in three cases. This is based on two independent pieces of evidence: a significant residual intensity in the cores of the strongest interstellar absorption-lines tracing neutral gas and a small ratio of extinction-corrected Hα to UV plus far-IR luminosities. These objects represent three of the four LBAs that contain a young, very compact (∼102 pc), and highly massive (∼109 M☉) dominant central object (DCO). These three objects also differ from the other galaxies in showing a significant amount of blueshifted Lyα emission, which may be related to the low covering factor of neutral gas. All four LBAs with DCOs in our sample show extremely high velocity outflows of interstellar gas, with line centroids blueshifted by about 700 km s−1 and maximum outflow velocities reaching at least 1500 km s−1. We show that these properties are consistent with an outflow driven by a powerful starburst that is exceptionally compact. We speculate that such extreme feedback may be required to enable the escape of ionizing radiation from star-forming galaxies.


We present the case of a 13 year old patient with myocardial bridge in left anterior descending coronary artery, who develops a myocardial infarction after a cardiothoracic trauma. About 24 hours after admission for trauma, an Electrocardiogram (ECG) showed an ST-segment elevation on anterior-lateral leads and QS complex referable to anterior-septal infarction, and an increase in troponin T serum levels was noted. An impaired left ventricular ejection fraction with diffuse regional wall motion abnormalities involving the left ventricular apex and interventricular septum were seen at transthoracic echocardiography. Contrast enhanced cardiac magnetic resonan-ce showed a widespread myocardial edema and necrosis at the level of left ventricular apex and interventricular septum. Intramural hemorrhage and signs of microvascular damage were found mainly at the mid-ventricular level of the antero-septal and anterior segments of myocardium. The coronary angiography revealed normal coronary arteries except for a myocardial bridge on distal part of left anterior descending coronary artery. A myocardial infarction with hemorrhage and microvascular damage was diagnosed, but the absence of a correspondence between site of the most severe myocardial injury and distal location of myocardial bridge was noted. Whether myocardial infarction and microvascular damage have been caused only by traumatic hit, or also by the contribution of myocardial bridge, is unknown. An intense constriction of left anterior descending coronary artery at the level of myocardial bridge could have determined thrombus formation with subsequent septal and distal embolization and myocardial infarction.


Dyscalculia, or mathematics learning disability, has received growing attention in recent years. Working memory and number sense are hypothesized to form important determinants of dyscalculia, but longitudinal assessments of number sense in children with or at-risk for dyscalculia are scarce. The current study investigated number line development in first and second grade, in addition to kindergarten predictors and mathematical proficiency as an outcome. Children (n = 396) could be divided into three latent growth classes: at-risk, catch-up, and typical, based on their number line development. Growth was predicted by kindergarten number sense and verbal working memory. According to the class to which they were assigned, children differed in mathematical proficiency at the end of grade 2. The current study makes an important contribution to the understanding of risk for dyscalculia, showing that children at-risk can be distinguished based on their number line development, and that kindergarten variables ar...


We propose a new framework for differentially private optimization of convex functions which are Lipschitz in an arbitrary norm $\|\cdot\|$. Our algorithms are based on a regularized exponential mechanism which samples from the density $\propto \exp(-k(F+\mu r))$ where $F$ is the empirical loss and $r$ is a regularizer which is strongly convex with respect to $\|\cdot\|$, generalizing a recent work of [Gopi, Lee, Liu '22] to non-Euclidean settings. We show that this mechanism satisfies Gaussian differential privacy and solves both DP-ERM (empirical risk minimization) and DP-SCO (stochastic convex optimization) by using localization tools from convex geometry. Our framework is the first to apply to private convex optimization in general normed spaces and directly recovers non-private SCO rates achieved by mirror descent as the privacy parameter $\epsilon \to \infty$. As applications, for Lipschitz optimization in $\ell_p$ norms for all $p \in (1, 2)$, we obtain the first optimal privacy-utility tradeoffs; for $p = 1$, we improve tradeoffs obtained by the recent works [Asi, Feldman, Koren, Talwar '21, Bassily, Guzman, Nandi '21] by at least a logarithmic factor. Our $\ell_p$ norm and Schatten-$p$ norm optimization frameworks are complemented with polynomial-time samplers whose query complexity we explicitly bound.


Artocarpus lakoocha Roxb. belongs to family ofMoraceae. It is commonly called asMonkey jack. Artocarpus lakoocha Roxb. is a perennial tree found on west coast fromKokan southwards to Kerala and Tamil Nadu. In present study, a HPTLC method has been developed and validated for simultaneous determination of â-sitosterol and Lupeol in the bark powder of Artocarpus lakoocha Roxb. plant. Chromatographywas performed on silica gel 60 F254 HPTLCplate, with toluene:methanol, 8:1 (v/v), asmobile phase. After development, plates were treated with Lieberman-Burchard Reagent, detection and quantification were performed by densitometry at 366 nm in fluorescencemode. The method was validated in terms of its linearity, limits of detection and quantification and precision following standard protocols. â- Sitosterol and Lupeol was found to be linear in the range of 10 µg mL-1 – 40µg mL-1 for both. Average content of â- Sitosterol and Lupeol in Bark powder of Artocarpus lakoocha Roxb. was found to be 0.106 mg and 0.242 mg respectively. The method was found to be simple, faster, precise, sensitive, and accurate and can be used for routine quality control of herbal raw materials and for the quantification of these compounds in plant materials.


We combine dependent types with linear type systems that soundly and completely capture polynomial time computation. We explore two systems for capturing polynomial time: one system that disallows construction of iterable data, and one, based on the LFPL system of Martin Hofmann, that controls construction via a payment method. Both of these are extended to full dependent types via Quantitative Type Theory, allowing for arbitrary computation in types alongside guaranteed polynomial time computation in terms. We prove the soundness of the systems using a realisability technique due to Dal Lago and Hofmann. Our long-term goal is to combine the extensional reasoning of type theory with intensional reasoning about the resources intrinsically consumed by programs. This paper is a step along this path, which we hope will lead both to practical systems for reasoning about programs' resource usage, and to theoretical use as a form of synthetic computational complexity theory.


Statement of the problem: Both the medical and psychological literature has indicated that stress impacts people's wellbeing. HIV positive individuals are among the most heavily stressed people. Stress comes from various sources such as relationships, lack of acceptance by family and friends, as well as other worries of day to day living (Lazarus and Folkman, 1984). However, stress has not been extensively researched in Zambia to examine its effects on neurocognitive functioning among individuals living with HIV and AIDS. Moreover, although social support has been found to reduce disease progression among chronically ill cancer patients, little is known about the interaction effects of social support and stress on neurocognitive functioning among HIV positive individuals. Objective: This study sought to examine the effects of stress and social support on neurocognitive functioning among HIV positive individuals in Lusaka, Zambia. Methods: Sample of the study consisted of 263 men and women (men= 107, women= 156) from six Clinics in Lusaka district. Their age ranged between 20 to 65 years. Their education was at least 5 years of schooling and above. This was a crosssectional study. The International neurobehavioural test battery was used to assess neurocognitive functioning. It assessed the neuropsychological performance of participants by administering various neuropsychological tests that measure brain function. Other measures included Perceived Stress Scale (PSS10) for stress and Medical Outcome Study Social Support Survey (MOSSS) for social support. ANOVA, Ttest and other statistics were used to analyse data with the help of SPSS version 16. Results: The results also indicated that stress has a significant relationship with working memory and verbal fluency, but not with other neurocognitive domains. Social support and its interaction with stress has no effect on neurocognitive functioning. Marital status was also related to stress and social support. The divorced group reported high stress (although the results were not statistically significant) levels and low social support received. The married group reported low stress levels and high social support. The results indicated that stress levels between participants did not differ by gender. Males and females were equally stress. Conclusion: HIV and AIDS affects neurocognitive functioning. Although the sample was mildly stressed, stress was significantly associated with working memory and verbal fluency. It is recommended that future study should consider the chronically stressed individuals to better understand the relationship between stress and neurocognitive dysfunctions. It is also recommended that government and other service providers continue the process of counseling even after the HIV positive individual has started antiretroviral.


This paper presents a hybrid modulation technique consisting of singe-reference six-pulsemodulation (SRSPM) for front-end dc/dc converter and 33% modulation for three-phase inverter. Employing proposed novel SRSPM to control front-end dc/dc converter, high frequency (HF) pulsating dc voltage waveform is produced, which is equivalent to six-pulse output at 6× line frequency (rectified 6-pulse output of balanced three-phase ac waveforms) once averaged. It reduces the control complexity owing to single-reference three-phase modulation as compared to conventional three-reference three-phase SPWM. In addition, it relives the need of dc-link capacitor reducing the cost and volume. Eliminating dc link capacitor helps in retaining the modulated information at the input of the three-phase inverter. It needs only 33% (one third) modulation of the inverter devices to generate balanced three-phase voltage waveforms resulting in significant saving in (at least 66%) switching losses of inverter semiconductor devices. At any instant of line cycle, only two switches are required to switch at HF and remaining switches retain their unique state of either ON or OFF. Besides, inverter devices are not commutated when the current through them is at its peak value. Drop in switching loss accounts to be around 86.6% in comparison with a standard voltage source inverter (VSI) employing standard three-phase sine pule width modulation. This paper explains operation and analysis of the HF two-stage inverter modulated by the proposed novel modulation scheme. Analysis has been verified by simulation results using results demonstrate effectiveness of the proposed modulation.


In recent times, the menace of job insecurity has become an important topic within sociology of industry, sociology of work and occupation, media sources, commentators and many observers because of the disastrous effects associated with deindustrialization. This study was designed to investigate the effect of deindustrialization of peripheral nations. Secondary sources of data were purposely collected and conflict perspective was employed in analyzing the study. The study revealed that employment in knowledge-based services is higher in recent decades compare to manufacturing industries. Technological changes often displaced workers (manual) from existing jobs. Unemployment and underdevelopment are tied to displacement of workers which result to social problems. It was recommended that peripheral Nations should develop their local technology to accelerate development instead of depending on western paradigm which denies majority (manual) workers employment opportunities. More so, Government in less-Developed societies should be committed to National policy on science and technology aimed at enhancing full industrialization that can generate employment opportunities for both manual and services information workers in order to avert the catastrophic negative effects associated with deindustrialization.


Abstract

In keeping with the ethos of the Higher Education Funding Council for England (HEFCE), related Key Information Sets (KIS) and National Student Survey (HEFCE 2012), the local university's five year strategic plan 2011-15 (Strategic Plan 2011) includes at its heart investing in the student experience with a curriculum that is flexible and responsive to changes both within and outside the university, and offering a 'high quality university experience' through innovative methods of learning. As part of a varied array of teaching, learning and assessment facilities, the university boasts of skills lab services which increasingly provide a unique opportunity for student midwives to practice clinical skills in a safe environment which ultimately prepares them to be fit for practice at the point of registration (Nursing and Midwifery Council (NMC) 2009). However, there has not been a formal evaluation of this service to date.

Purpose

This study set out to evaluate the current service provided for pre-registration midwifery students in the university skills lab in order to establish current standard, provide a benchmark for future development, and contribute to the students' learning experience.

Methodology

Using a case study approach, a representative convenient sample of users of the service was studied. Participants included 7 third year and 3 first year students from the pre-registration midwifery programme based on one of the two university campus sites, and 2 midwifery lecturers plus 2 skills lab support staff working across both campuses. All participants were asked about their experience of using the skills labs. Interviews were transcribed verbatim and analysed using a thematic approach and NVivo software. Student focus groups and staff one-to-one interviews were carried out, as well as observation of activity in the skills lab. Relevant document analysis was also undertaken.

Findings

The main themes emerging from analysis of the data include the following: both staff and students felt that there was more theory than practice in the teaching and learning activities in the skills lab; that the management of time and communication around the assessment process in the skills lab could be improved; that the quality and authenticity of equipment and facilities could be improved; that capacity issues, consisting of an interaction between student numbers, time and space management in the lab, had a negative impact on the learning experience; and that better communication amongst users overall could further improve the service.

Implications

Whilst some of the findings support the literature, there appears to be some new information particularly related to student perceptions of the theory - practice ratio of sessions, and capacity issues impacting on learning. The author makes several recommendations for educational institutions providing a skills lab service including the following: Educational institutions should
• explore innovative teaching strategies such as the blended approach which would allow more time for students to spend on hands-on practice in the lab,
• explore strategies to enhance the authenticity of the equipment to improve the students' learning experience in the lab,
• develop better communication systems and appropriate management of timetables, coupled with clear guidelines for staff-student ratios in order to address capacity issues; clear communication around assessment that takes into account individual students' unique needs must also be ensured.

Limitations

The author recognises that this study was primarily based on the experience of students from one out of two university campuses admitting pre-registration midwifery students. This was due to time constraints related to the timetable for the Master's study. It would therefore be useful to consider further research that encompasses the experience of students from both campus sites as well as addressing possible issues surrounding parity of experience across sites.


The publication of a new British textbook of clinical cardiology is an event of major importance. The author, who is senior physician and director of the cardiac department, King's College Hospital, London, describes his aim as "a reasonably comprehensive book with a strong bedside bias" and expresses the hope that it may be useful to undergraduate as well as to postgraduate students. Clinical Heart Disease is indeed a comprehensive textbook-comparable in size to "Paul Wood"-and it represents a monumental achievement by a single compiler. Cardiac and respiratory investigations are fully described; surgical treatment, anaesthesia for cardiac patients, and peripheral vascular disease are all adequately covered. It is an easy book to read; and the material is set out in a manner designed to aid learning, with free use of italics, some good aphorisms, and a few mnemonics. The style is refreshingly dogmatic. For example, in the chapter on clinical examination, the author says: "The practice of describing the apex beat as so many inches from the mid-line should be abandoned"; and "The hepatojugular reflux is useless for the detection of early heart failure." Of the mnemonics, a good example is the word "Cassius"-as an aid to recalling the remediable causes of hypertension; another is "Two A's and five T's"-for the differential diagnosis of cyanosis due to right to left shunts in infants. Each chapter ends with a list of 10 to 20 "Salient Features" and select references. Inevitably, there are places where the author's dogma will be disputed by other experts: for instance, the statement "The apex beat has position only, not character"; and "It is unsafe to diagnose an Austin Flint murmur unless the aortic incompetence is syphilitic." Inevitably, too, the time lag between completion of the manuscript and publication of the book has rendered parts out of date. Thus, in the section on the recording of the blood pressure, it is stated that the United Kingdom is exceptional in accepting the fourth phase as indicating the diastolic level. This was so for a number of years; but in 1967, the American Heart Association recommended adoption of the British practice. A notable omission is the subject of the hemi-blocks. These deficiencies will no doubt be remedied in a second edition. Clinical Heart Disease is adequately illustrated, though there is a certain amount of unnecessary duplication. The black and white line diagrams and pressure recordings are clear, and so are the electrocardiograms. On the other hand, some of the x-rays and many of the phonocardiograms are of poor quality. It is a good comprehensive textbook for the postgraduate student and a useful reference book for the general physician and the practising cardiologist. The undergraduate, on the other hand, will probably find it too detailed for his purpose, and too expensive for his pocket.


We study the power of state-dependent unemployment insurance (UI) to stabilize short-run fluctuations, allowing for arbitrary deviations from full information and rational expectations. Expectations are critical because higher UI generosity raises consumption, to a large extent, by lowering precautionary savings. If UI generosity is indexed to the unemployment rate, households must forecast the unemployment rate to anticipate the policy stance. We estimate unemployment expectations in response to identified aggregate shocks. We quantify the consequences of these imperfect expectations through the lens of a Heterogeneous Agent New Keynesian model. First, we work directly with the estimated forecast errors. Our methodological contribution is to use the non-parametric history of forecast errors and forecast revisions to solve dynamic decisions of optimizing agents. By doing so, we sidestep the need to choose a particular model of belief formation. The estimated model implies that imperfect anticipation substantially affects the stimulative power of UI extensions. Second, we compare alternative ways of implementing UI policies. To run counterfactuals, we estimate a structural model of belief formation. We show that a combination of noisy information and diagnostic expectations fits the data best among a large set of popular alternatives. A UI extension that is announced directly is more stimulative in the very short run than one that is indexed to the unemployment rate.


Universitatsverlag Gottingen T book brings together information about the latest academic library building projects from across Europe. New attractive buildings and huge renovation projects are presented in this documentation which continues the tradition established by Professor Elmar Mittler (formerly Director of the State and University Library Gottingen), who was the first chairman of the LIBER Architecture Group. The publication of this book coincides with the 15th LIBER Architecture Group Seminar which will take place in Madrid in April 2010. In addition to hearing about the latest developments in planning and design and offering visits to new library buildings, the Seminar provides an occasion to debate ideas and meet colleagues from institutions across Europe. I hope that the projects in this book will provide ideas for your own work and that they will also stimulate your interest in new library architecture and the creative use of space. New Library Buildings in Europe


Several data emphasize the neuroendocrine aspects of human placenta. Classical hypophyseo‐tropic neurohormones are produced and secreted by the human placenta. Indeed, in contrast with non pregnant subjects, gonadotropin‐releasing hormone (GnRH) and corticotropin‐releasing factor (CRF) are measurable in maternal plasma during pregnancy. The aim of the present study was to investigate the characteristics of the secretory pattern of maternal plasma GnRH and CRF levels. A total of 25 healthy pregnant women participated in the present cross‐sectional study. Plasma levels of the two neurohormones were measured according to three different time‐intervals: 1) every five minutes for eight hours (n=4), 2) every ten minutes for four hours (n= 15), 3) every four hours for 24 hours (n =7). Following an acidic extraction plasma GnRH and CRF levels were measured by specific radioimmunoassay. Using two different algorithms (Detect and Cluster) a pulsatile pattern for both plasma GnRH and CRF levels was observed. Specific pulse frequency, amplitude, and duration were found. In the groups of women studied with a longer sampling interval, pulse frequency of GnRH or CRF levels did not differ between first and third trimester of gestation. However, amplitude of CRF pulses were significantly higher at term than at early stages of pregnancy (p≤0.01), while GnRH pulse amplitude was highest in women at first trimester of gestation. Evaluating the degree of concordance in all subjects, GnRH pulses significantly correlated with CRF pulses at 30 min. lag (p≤0.01). No significant circadian changes were found for any circulating neurohormone measured. The present study showed that maternal circulating neurohormone levels change according to a pulsatile pattern, probably reflecting the placental secretory events.


In this paper, an efficient extension of network simplex algorithm is presented. In static scheduling problem, where there is no change in situation, the challenge is that the large problems can be solved in a short time. In this paper, the Static Scheduling problem of Automated Guided Vehicles in container terminal is solved by Network Simplex Algorithm (NSA) and NSA+, which extended the standard NSA. The algorithms are based on graph model and their performances are at least 100 times faster than traditional simplex algorithm for Linear Programs. Many random data are generated and fed to the model for 50 vehicles. We compared results of NSA and NSA+ for the static automated vehicle scheduling problem. The results show that NSA+ is significantly more efficient than NSA. It is found that, in practice, NSA and NSA+ take polynomial time to solve problems in this application.


The invention discloses methods and apparatuses for verifying and creating safe articles. A method and apparatus for determining a digital signature from an article made of paper, cardboard, plastic or many other material types. A coherent source directs a beam to illuminate the article and a detector arrangement collects data points from light scattered from many different parts of the article to collect a large number of independent data points, typically 500 or more. By collecting a large number of independent signal contributions specific to many different parts of the article, a digital signature can be computed that is unique to the area of the article that has been scanned. This measurement can be repeated whenever required to test authenticity of the article. Using this method, ithas been discovered that it is essentially pointless to go to the effort and expense of making specially prepared tokens, since unique characteristics are measurable in a straightforward manner from a wide variety of every day articles.


Visible-infrared cross modality person re-identification (VI-ReID) is a core but challenging technology in the 24-hours intelligent surveillance system. How to eliminate the large modality gap lies in the heart of VI-ReID. Conventional methods mainly focus on directly aligning the heterogeneous modalities into the same space. However, due to the unbalanced color information between the visible and infrared images, the features of visible images tend to overfit the clothing color information, which would be harmful to the modality alignment. Besides, these methods mainly align the heterogeneous feature distributions in dataset-level while ignoring the valuable identity information, which may cause the feature misalignment of some identities and weaken the discrimination of features. To tackle above problems, we propose a novel approach for VI-ReID. It learns the color-irrelevant features through the color-irrelevant consistency learning (CICL) and aligns the identity-level feature distributions by the identity-aware modality adaptation (IAMA). The CICL and IAMA are integrated into a joint learning framework and can promote each other. Extensive experiments on two popular datasets SYSU-MM01 and RegDB demonstrate the superiority and effectiveness of our approach against the state-of-the-art methods.


The diagnostic value and technical versatility of the previously described telescopic catheter system was demonstrated in 15 patients by super-selective angiography of the external carotid artery. It was possible in all patients to catheterise the individual branches with the F-catheter; the polyethylene-S-catheter could then be passed 3 to 5 cm, beyond the tip of the F-catheter. In almost half the patients, spasm of the injected artery was observed, particularly of the superficial temporal and external occipital arteries; this was reversed by intravenous papaverine and did not interfere with detailed diagnosis. It was usually possible to obtain filling of peripheral vessels, thereby demonstrating the territory of the middle meningeal artery, the scalp, sub-mandibular gland and the pinna. There were no complications as a result of the catheterisation. The usefulness and advantages of the telescopic catheter system for therapeutic neuro-radiological procedures, with embolisation of external branches in man, are discussed.


Author(s): Bernstein, Laurence Elliot | Advisor(s): Bandeira, Nuno; Briggs, Steven | Abstract: Tandem mass spectrometry (MS/MS) has long been the leading method of identifying peptides and proteins in complex biological samples and many algorithms have been created for this purpose. Many of the methods for searching MS/MS spectra against a database of known proteins must restrict the number of post-translational modifications (PTMs) that they can identify because the larger the number of PTMs being considered, the larger the search space, which in turn increases both computational complexity and the potential for false matches. In addition these algorithms cannot discover new peptides or homologues or be used with species for which a protein database does not exist. Newer algorithms have been developed that perform "open" or "blind" searches capable of finding any possible modifications, however these methods increase the search space even further, often resulting in lower performance and the generation of many putative modification masses that must be sifted through manually to determine which are real. To address the shortcomings of the existing methods, we created a new blind database search algorithm based on spectral networks. Our method uses a modification of the standard spectral tagging filtration techniques tailored for contig-consensus spectra generated from spectral networks, along with, the first of its kind, penalty-based, dynamic programming spectrum-database alignment algorithm that is able to accurately to identify both a priori specified modifications as well as novel PTMs. We then developed a workflow based on these new techniques that combines previous work in clustering, spectral alignment, spectral networks, and multi-spectral assembly. Because our new algorithm only identifies spectra that lie within the spectral networks, we created a workflow, called RaVen, that merged our method with MS-GF+ and combines the results from both methods resulting in a method with massive improvement in overall identification rates above existing methods while at the same time identifying many more rare modifications in samples. We also propose an improved way of measuring the accuracy of blind search algorithms: "peptide variants" which better meet captures the goals of blind search methods and does not rely on precise localization of modifications (which is very difficult to achieve for most algorithms).


A case of appendiceal abscess presenting leukemoid reaction is reported. A seven-month-old male infant was admitted because of fever and diarrhea. Anemic conjunctiva and mild abdominal distension were the only physical findings on arrival. Progressive leukocytosis with left shift maturation was noted during hospitalization. The maximal white blood cell count was 178,000/cumm, with a high leukocyte alkaline phosphatase score. On the fourth day of admission, a palpable right lower quadrant abdominal mass with local tenderness was found. Appendiceal abscess was diagnosed by both ultrasonography and computed tomography. The infant received triple antibiotic therapy consisting of ampicillin, gentamicin, and clindamycin for 10 days; the mass disappeared two weeks later. As appendiceal abscess is a rare occurrence in infants and its production of a leukemoid reaction is even rarer, the case described here may cause a diagnostic challenge, and deserves attention from clinicians.


First-person video naturally brings the use of a physical environment to the forefront, since it shows the camera wearer interacting fluidly in a space based on his intentions. However, current methods largely separate the observed actions from the persistent space itself. We introduce a model for environment affordances that is learned directly from egocentric video. The main idea is to gain a human-centric model of a physical space (such as a kitchen) that captures (1) the primary spatial zones of interaction and (2) the likely activities they support. Our approach decomposes a space into a topological map derived from first-person activity, organizing an ego-video into a series of visits to the different zones. Further, we show how to link zones across multiple related environments (e.g., from videos of multiple kitchens) to obtain a consolidated representation of environment functionality. On EPIC-Kitchens and EGTEA+, we demonstrate our approach for learning scene affordances and anticipating future actions in long-form video.


While it is rarely indicated today, fenestration of the horizontal semicircular canal has left its mark in otologic history. A significant number of patients with fenestrated ears are alive today requiring continued care. A review of both the technique of fenestration as well as the particular postoperative problems is presented to familiarize younger otologists involved in their management.


Background Return to sport after serious knee surgery which is anterior cruciate ligament reconstruction (ACLR) is very difficult and sometimes unsuccessful process. Main goals of postoperative period is to restore balance, limb symmetry of hamstrings and quadriceps strength and power. Player's recovery to pre-injury level in term of specific sport performance as well as mental awareness of re-injury is a difficult task. From strength and conditioning perspective, landing technique, sudden changes of movement direction are crucial abilities for sport participation and should be sustained on high level after return to play. Objectives We aimed to assess mid-term functional outcomes after ACLR in professional football players with sport performance outcome – time on the pitch; first team appearances seasons after surgery in comparison to season before injury. Methods Group I included 17 players who had undergone isolated ACLR using semitendinosus (ST) ipsilateral autograft and successfully return to sport. Postoperatively, they participated in full time professional physical therapy, resulted in return to sport and competition. Group II included 25 players without severe knee ankle injuries. The two groups were matched for age and body mass index (BMI). Functional tests – Figure of 8 Hop Test, Side-Hop and quadriceps/hamstrings torque under isometric conditions measurements were performed at a mean of ±32 months postoperatively (min.23 months). Research of sport participation were conducted to set every player real time's spent on the pitch, based on match protocols, football database's. Results The limbs with the ACLR had greater LSI = 3% for quadriceps and LSI = 10% for hamstrings isometric torque as compared to uninjured side (p = 0.389, p = 0.077 respectively). The subjects with ACLR had non-significantly higher (p = 0.319) values with regard to dominant side quadriceps and non-significantly lower (p = 0.414) hamstring's peak torque respectively in inter-group comparison. Results of the hop tests showed nonsignificant intra-group side to side differences and significantly faster Side-Hop test performance for Group II in inter-group operated/kicking side comparison (p = 0.028). Return to training in ACL group was ±7,2 months. Return to match/match time – ±8,30 months/ ±32,0 min. Match Time in percentage of pre-injury season - return to sport season 55%, second season after return 92% vs preinjury, at follow-up 104%. Conclusions At the time of follow-up, the ACLR group had worse functional outcomes in terms of hamstring strength and the results of the Figure of 8 Hop Test, Side-Hop Test. However, bigger inter limb asymmetry was found in non-ACL group with kicking side domination higher than 10% for hamstrings. Soccer player after ACL reconstruction in this cohort had 55% pitch time in return to sport season relatively to preinjury time. Second and at follow-up season time spend on pitch was 92 and 104% respectively as compared to preinjury season. Intergroup comparison revealed that soccer players who had undergone ACLR had less quadriceps and hamstrings strength and worse hop performance.


PURPOSE
Pre-participation health screening is recommended to detect individuals susceptible to serious adverse cardiovascular complications during exercise. Although expert opinion and best available scientific evidence have informed recent modifications, there remains limited experimental data to support or refute current practice. We therefore aimed to quantify the impact of change to the ACSM pre-participation health screening guidelines on risk classification and referral for medical clearance in a large cohort of undergraduate university students.

METHODS
Participants attended the laboratory on a single occasion to undergo pre-participation health screening. Information concerning health status was obtained via self-report questionnaire and objective physiological assessment with all data recorded electronically and evaluated against ACSM screening guidelines (9 and 10 Edition).

RESULTS
Five-hundred and fifty-three students completed the study. The 9th Edition screening guidance resulted in eighty-two (15%) subjects classified as high-risk, almost one quarter (24%) classified as moderate-risk, and almost two-thirds (61%) classified as low-risk. In comparison, the updated 10 Edition screening guidance resulted in a significant reduction in those previously classified as either high-risk (5%) or moderate risk (2%), respectively. The majority of subjects (93%) were therefore cleared to begin a structured exercise programme. Taken together, approximately one-third (32%) fewer medical referrals were required when applying the updated 10 Edition guidance (χ (4) = 247.7, P<0.001).

CONCLUSION
The updated ACSM 10 Edition pre-participation screening guidance reduces medical referrals by approximately one-third. These findings are in keeping with previous reports and thus serve to consolidate and justify recent modification - particularly when applied to young adult or adolescent populations. The findings and arguments presented should be used to refine and inform future guidance.


Social surveys and interviews are staple methods within health research. One of the perceived merits of the postal questionnaire is the anonymity it affords to participants, enabling people to provide honest accounts, particularly in relation to sensitive topics. Interviewing can potentially introduce bias to participants' accounts because of a compulsion to provide socially desirable responses. Here we examine these assumptions through a comparison of questionnaire and interview accounts of the help-seeking experiences of people with symptoms of cancer. Public discourses of early diagnosis of cancer are increasingly commonplace, particularly after the 'Be Clear on Cancer' campaigns, which reinforced the importance of consulting quickly when experiencing cancer symptoms. This study aimed to explore the help-seeking experiences of people with symptoms of lung or colorectal cancer by inviting patients to complete a questionnaire about their symptom onset and first consultation with a health care practitioner. A sub sample of these participants were interviewed about their help-seeking experiences, with the interviews taking place within 8 weeks of the questionnaires being returned. We found that the reported length of the help-seeking interval (time from first symptom to first consultation with a health care practitioner) differed in questionnaire and interview accounts for the majority of participants. Whilst we may have expected participants to report longer intervals in the questionnaire, because of its perceived ability to reduce social desirability bias, we found that the converse was true; for most of the cases where there was a discrepancy in interval length between questionnaire and interview, longer help-seeking intervals were reported in the interview. We shall consider possible explanations for these unexpected results, suggesting that the concept of 'public accounts' and 'private accounts' provides insight into these discrepant participant responses. The formality of the questionnaire and the closed nature of questioning may encourage participants to report more socially acceptable behaviours in order to conform to public discourses around early help-seeking and early diagnosis. Whereas in interviews, participants were able to report more deviant accounts because they were within the private setting (their homes) and were able to narrate their stories and detail their reasoning.


. Investigating effects of grape seed extract on neuropathic pain in the streptozotocin-induced diabetic mice. Yurt A., Köksal B., Gürbüz P., Yıldız A., Vardı N., Alçin E. Diabetes mellitus is a complicated and serious health problem involving peripheral neuropathy. This situation causes to loss of senses, tingle and pain. Diabetic peripheral neuropathy (DPN) affects 236 million people around the World. Hence there is a need to investigate alternative ways of cure focusing on DPN. Flavonoids have potential on pain due to their permeability characteristic in the capillary microcirculation system and in lowering blood pressure. Flavonoids are common in grape seed. The main flavonoids of grape seed involve proanthocyanidins which might be an effective agent in cure of pain in DPN. The purpose of this study is to investigate effects of grape seed extract on neuropathic pain in the Streptozotocin-induced diabetic mice. In the study, 50 eight-week old BALB-C strain mice in five different groups (Control, Diabetic Control, Control+25 mg/kg, Diabetes+25 mg/kg and Diabetes+50 mg/kg) were used. To induce diabetes in thirty of these animals, single dose Streptozotocin (180 mg/kg) was administered intraperitoneally. After diabetes was observed, grape seed extract (25 mg/kg and 50 mg/kg body weight) was administered by oral gavage in three groups (Control+25 mg/kg, Diabetes+25 mg/kg and Diabetes+50 mg/kg) during six weeks. At the end of the second and sixth weeks, pain threshold measurements in hot plate test were performed in line with a predetermined thermal pain model. Also the tissues of the sciatic nerve and abdominal aorta from the animals were histologically investigated. As a result hot plate measurements, pain threshold values of the animals in Diabetes+50mg/kg group significantly differed from the measurements of the animals in control group in the first measurements and from the animals in Diabetes+25 mg/kg group in the second measurements (p<0.05). However pain threshold values of the animals in Diabetes+25 mg/kg group differed significantly from the values of the animals in control+25 mg/kg group and control group. It means pain threshold values of the animals in Diabetes+50 mg/kg and Diabetes+25 mg/kg groups were significantly lower than the values of the animals in the other groups. The results of histological investigations showed that degenerations of myelin sheet and axons in diabetic control group were decreased significantly in Diabetes+50 mg/kg and Diabetes+25 mg/kg groups. Moreover degenerations of aorta tissues of animals in diabetic group were not seen in the animals of Diabetes+50 mg/kg except for tunica adventitia inflammation. It can be said that grape seed extract decreased threshold of neuropathic pain in the Streptozotocin-induced diabetic mice and prevented degenerations of myelin sheet and axons, and aorta tissues.


Wireless sensor and actuator networks have expanding applications which requires better throughput, power efficiency and cost effectiveness. This study intends to contribute to the growing pool of knowledge on WSAN especially in the design for novel applications such as image or video over WSANs, and solar energy and RF energy harvesting for the WSAN nodes. Two basic scalable wireless sensor and actuator networks were implemented and characterized in terms of throughput and power consumption. The two WSANs are the Zigbee-based WSAN which is based on the IEEE 802.15.4 protocol, and the ISM-based Zigbee which makes use of the industrial, scientific and medical (ISM) radio bands. The star topology was used for both WSAN implementations. The throughput is quantified with varied factors including distance from node to node, obstructions in between nodes and co-channel interference. As distance and obstructions between nodes are increased, the throughput for both networks decreases with varying degrees. Co-channel interference is also considered. The ISM-based WSAN network is weak in dealing with co-channel interference and error rate as compared to the Zigbee-based WSAN, thus requiring it to have a better data encryption. Power consumption is generally larger for the ISM-based WSAN as compared to its Zigbee-based counterpart. However, the ISM-based nodes consume the same power even up to a few hundreds of meters distance and are thus practical for covering large distances. Therefore, the Zigbee-based WSAN system is more appropriate for closed environment, such as in room automation and home automation applications where distance from node to node is relatively shorter. The ISM-based WSAN prototype, on the other hand, can be developed further for applications in larger areas such as deployment in fields and cities, since transmission is not generally limited by distance and obstructions.


An existing finite-element solver for steady, non-linear subsonic flow is extended in order to treat unsteady potential flow problems in the Laplace domain. The numerical formulation makes use of unstructured meshes including explicitly modelled, triangulated wake surfaces. Meshes can contain both linear and quadratic volume and surface elements, thus allowing to favor either very fast solution times or high spatial resolution. Aeroelastic problems are dealt with by modelling moving or deforming bodies by means of transpiration boundary conditions. Deformations of the aerodynamic mesh are computed either by projection of aerodynamic mesh nodes onto the finite elements of a structural shell model, or by radial basis function interpolation suitable for beam-type structural models. In addition to simple validation cases, an application of the solver for the evaluation of gust loads on a commuter aircraft is presented. In order to evaluate the use of the method in the context of a relevant, industrial-scale load analysis, typical geometrical and structural models for a twin-turboprop aircraft in the 15t-class (e.g. Saab 340, CN-235, Dash 8, Do 328) are employed.


The developmental changes in the activity of kidney transamidinase in male and female rats were investigated. The activity in both sexes increased rapidly after birth, reaching adult levels at 4 days of age. After weaning, the activity in male rats remained constant, while in female rats it declined to 60% of that in males. Thus, transamidinase is in the neonatal cluster of enzyme differentiation.


The normal microscopic and macroscopic changes that occur with aging and the neurophysiological effects of these neuroanatomical changes are described. Among the microscopic changes are dendritic and neuronal losses, thinning of axons and myelin sheaths; a decrease in the number of receptors and amount of neurotransmitter available together with the appearance of lipofuscin, granulovacuolar organelles, neurofibrillary tangles and senile plaques. Macroscopic changes include decreases in the weight and volume of the brain, thinning of the cortical mantle and white matter tracts, widening of sulci and fissures, and meningeal thickening. Neurophysiologically aging persons evidence decreased recent memory, a decreased ability to process information and an increased conduction time. These factors result in increased learning time, response time and, hence, recovery time. The major nursing implications of these neurophysiological changes for spinal cord injured persons relate to safety when mobilizing and engaging in self care and providing increased learning time.


Computational models whose organization is inspired by the cortex are increasing in both number and popularity. Current instances of such models include convolutional networks, HMAX, Hierarchical Temporal Memory, and deep belief networks. These models present two practical challenges. First, they are computationally intensive. Second, while the operations performed by individual cells, or units, are typically simple, the code needed to keep track of network connectivity can quickly become complicated, leading to programs that are difficult to write and to modify. Massively parallel commodity computing hardware has recently become available in the form of general-purpose GPUs. This helps address the first problem but exacerbates the second. GPU programming adds an extra layer of difficulty, further discouraging exploration. To address these concerns, we have created a programming framework called CNS ('Cortical Network Simulator'). CNS models are automatically compiled and run on a GPU, typically 80-100x faster than on a single CPU, without the user having to learn any GPU programming. A novel scheme for the parametric specification of network connectivity allows the user to focus on writing just the code executed by a single cell. We hope that the ability to rapidly define and run cortically-inspired models will facilitate research in the cortical modeling community. CNS is available1 under the GNU General Public License.


Clearance of Chronic Virus The family of mRNA-editing enzymes, APOBEC, restricts hepatitis B virus (HBV) replication. Lucifora et al. (p. 1221, published online 20 February; see the Perspective by Shlomai and Rice) provide evidence that specific APOBECs mediate the anti-HBV effects of host cytokines, which in turn apparently induce nuclear deaminase activity without damaging host cells. Thus, there may be potential in these findings for developing a therapeutic route to curing chronic HBV infection. Cytokine induction renders viral DNA vulnerable and eliminates infection. Current antiviral agents can control but not eliminate hepatitis B virus (HBV), because HBV establishes a stable nuclear covalently closed circular DNA (cccDNA). Interferon-α treatment can clear HBV but is limited by systemic side effects. We describe how interferon-α can induce specific degradation of the nuclear viral DNA without hepatotoxicity and propose lymphotoxin-β receptor activation as a therapeutic alternative. Interferon-α and lymphotoxin-β receptor activation up-regulated APOBEC3A and APOBEC3B cytidine deaminases, respectively, in HBV-infected cells, primary hepatocytes, and human liver needle biopsies. HBV core protein mediated the interaction with nuclear cccDNA, resulting in cytidine deamination, apurinic/apyrimidinic site formation, and finally cccDNA degradation that prevented HBV reactivation. Genomic DNA was not affected. Thus, inducing nuclear deaminases—for example, by lymphotoxin-β receptor activation—allows the development of new therapeutics that, in combination with existing antivirals, may cure hepatitis B.


Summary Inventory management is considered to be an important field in Supply chain management. Once the efficient and effective management of inventory is carried out throughout the supply chain, service provided to the customer ultimately gets enhanced. Hence, to ensure minimal cost for the supply chain, the determination of the inventory to be held at various levels in a supply chain is unavoidable. Minimizing the total supply chain cost refers to the reduction of holding and shortage cost in the entire supply chain. Efficient inventory management is a complex process which entails the management of the inventory in the whole supply chain and getting the final solution as optimal, i.e. in the process of supply chain management, the stock level at each member of the supply chain should account to minimum total supply chain cost. The dynamic nature of the excess stock level and shortage level over all the periods is a serious issue when implementation is considered. In addition, the complexity of the problem increases when more number of products, distribution centers and agents are involved. Moreover, the supply chain cost increases because of the influence of lead times for supplying the stocks . A better optimization methodology would consider all these factors in the prediction of the optimal stock levels to be maintained in order to minimize the total supply chain cost. In this paper, these issues of inventory management have been focused and a novel approach based on Genetic Algorithm has been proposed in which the most probable excess stock level and shortage level required for inventory optimization in the supply chain is distinctively determined so as to achieve minimum total supply chain cost.


The present study was undertaken to determine the anti-microbial potential of the methanol extract of different plant parts of Pongamia Pinnata in vivo and in vitro. All the extractions were tested against different gram positive and gram negative bacteria and fungi to find out their antimicrobial activity using agar well diffusion and micro dilution method for fortitude the MIC value. The maximum antimicrobial activity of root extract was observed against E. coli and F. oxisporum while in leaf extract maximum antimicrobial activity was observed against S. aureus, B. cereus and A. solani. However, Callus extracts showed mild to moderate inhibitory effects against E. cloacae, P. aeruginosa, A. flavus and R. stolonifer. Besides these, the maximum antimicrobial activity of stem extract was observed only against A. niger. Flucanazole and Ampicillin standards were used as positive controls respectively for fungi and bacteria in this study.


The Truth and Reconciliation Commission made significant progress in examining abuses committed during the apartheid era in South Africa. Despite information revealed by the commission, a large number of individuals remained missing when the commission closed its proceedings. This provided the impetus for the establishment of a Missing Persons Task Team within the South African National Prosecuting Authority. The team has used evidence generated by The Truth and Reconciliation Commission as well as their own investigations to identify likely burial sites for activists and has conducted exhumations. The University of the Western Cape (UWC) was privileged to have been able to assist by initiating a DNA testing program to augment the non-DNA evidence gathered by the Missing Person's Task Team. In this review we consider some of the technological developments associated with the testing of skeletal remains and provide an overview of some of the cases analyzed to date.


Glucose homeostasis is regulated by the opposing actions of insulin and glucagon; insulin facilitates rapid glucose uptake from the blood stream to muscle and adipose cells. These tissues express the facilitative glucose transporter (GLUT4), which in response to insulin is translocated from intracellular compartments to the plasma membrane (PM) allowing glucose entry to cells. GLUT4 undergoes a complex intracellular trafficking itinerary, including recycling to and from the PM, but in the absence of insulin is mainly stored in GLUT4 storage vesicles (GSVs). When insulin binds its receptor, a complicated signalling cascade is initiated which results in the tethering, docking and fusion of GSVs to the PM. Fusion of the GSVs with the plasma membrane is mediated by SNARE proteins. The formation of a SNARE complex composed of Syntaxin4 (Sx4) and SNAP23 localised to the PM and VAMP2 on GSVs is a key event; the formation of this complex is in turn regulated by the Sec1/Munc18 protein, Munc18c. It has been shown that insulin stimulation leads to phosphorylation of Sx4 at two sites (Y115 and Y251) and Munc18c at Y521. The stoichiometry and order of phosphorylation are not yet known, and the biological consequences of this action to be uncovered. Therefore, the current study sought to ascertain the functional consequences of SNARE protein phosphorylation on GLUT4 trafficking. The approaches used include in vitro assessment of recombinant SNARE proteins and studies in vivo using 3T3-L1 adipocytes.
The results of this study confirmed that tyrosine 115 and 251 of syntaxin4 are phosphorylated in response to insulin in 3T3-L1 adipocytes; however, phosphorylation of Munc18c was ambiguous. Subsequently, phosphomimetic recombinant SNARE proteins were expressed and ternary SNARE complex formation was successfully recapitulated in vitro and the complex found to be SDS and heat resistant. Phosphomimetic syntaxin4 mutants showed increased formation of SNARE complexes, notably double phosphomimetic mutant. Moreover, binary interactions with other SNAREs (SNAP23 and VAMP2) revealed tighter binding and higher affinity of the double phosphomimetic syntaxin4 compared to wild-type syntaxin4. Additional spectroscopic evidences suggest these differences are due to conformational changes and syntaxin4 mutants are more likely to be in the open form especially the double phosphomimetic mutant.
In order to translate in vitro findings into cell models, in vivo intervention tools were generated including phospho-specific antibodies against phosphorylated residues in syntaxin4 and lentivirus particles for 3T3-L1 adipocytes infection. Antibodies validated on recombinant proteins phosphorylated using recombinant insulin receptor tyrosine kinase indicated they are functional and specific. Efforts dedicated towards optimizing working conditions for phospho-specific antibodies using adipocyte lysates were extensively examined, yet signals detected were generally found to be non-specific.
A non-intrusive protein-protein interaction protocol, proximity ligation assay, was used to detect insulin-stimulated phosphorylation in adipocytes. A positive signal was detected confirming antibodies functionality in this assay; further work will be required to optimize this.
Lentiviruses were used to over-express phosphomimetic mutants of syntaxin4 in 3T3-L1 adipocytes and Hela cells. The functionality of the transfected syntaxin4 mutants was assessed by measuring basal and insulin-stimulated glucose uptake. Infected native 3T3-L1 adipocytes showed a trend towards an increase in glucose uptake under basal conditions with no effect observed on the maximal insulin-stimulated rate of glucose transport. We speculate this may reflect the presence of the endogenous Sx4 molecules masking any effects of mutant over-expression thus Sx4 knockout cell lines was considered as an alternative experimental system. Sx4 overexpression rescued insulin-stimulated glucose uptake in Sx4 knockout 3T3-L1 cells and was significantly enhanced in cells expressing the double phosphomimetic mutant.
Finally, our work showed that the native Munc18c native mouse gene sequence expressed poorly in bacteria; hence we used a gene-enhanced sequence that was found to express well and purify effectively. CD spectroscopy showed similar structures of expressed Munc18c using either sequences. Phosphomimetic Munc18c (Y521E) binds with higher affinity both wild type and double phosphomimetic syntaxin4 compared to wild type Munc18c.
The data presented in this study suggest strongly that phosphorylation influences GLUT4 trafficking by altering the frequency and affinity of SNARE protein interactions. Such findings enrich knowledge about the mechanism of GLUT4 trafficking thus ultimately could help in understanding type 2 diabetes.