The presence of impurities, particularly the API-related impurities, i.e., degradation-related impurities (DRIs) and interaction-related impurities (IRIs), may affect the quality, safety, and efficacy of drug products. Since the regulatory requirements and management strategies are required to be established and complied, sources of impurities shall be carefully classified prior to take subsequent steps such as development of analytical methods and acceptance criteria. Current international regulatory requirements for the management of impurities in pharmaceuticals were reviewed. Procedures for the identification of DPIs in pharmaceuticals, i.e., ethyl cysteinate dimer, (R)-N-methyl-3-(2-bromophenoxy) -3-phenylpropanamine, sestamibi, etc., using high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) were studied. Scheme for the establishment of analytical methods and acceptance criteria of process-related impurities (PRIs) and DRIs in accordance with the requirements of International Council for Harmonization (ICH) and algorithm to perform the identification of DPIs by using LC-MS/MS has been proposed. Practice of kinetic study to distinguish PRIs and DRIs, determination of the potential core fragments coupled with a predicted list of relevant transformations for conducting MS/MS scans, applications of stable isotope distribution patterns or natural abundances, practice of mass balance, etc., have been well demonstrated to justify the reliabilities of identification results.


Natural-technological accidents, or NATECHs, reveal a particular exposure and vulnerability of industrial facilities to extreme, intense or localised natural hazards. This has been confirmed, in a recent past, by events such as the 1999 Izmit earthquake, the 2002 floods in Southeast France, and the 2004 hurricane Katrina in the U.S. In a way, NATECHs can be considered as an invitation to revisit fields of expertise usually featured in accidental risk analysis. Likewise, efforts devoted to risk reduction and emergency response should also benefit from a NATECH-specific look at industrial facilities. Despite a growing body of regulation for industry operation in hazard-prone areas, mitigation efforts still often address NATECH risks with stand-alone actions and mono-disciplinary approach. This paper advocates for a more integrated approach that features several disciplines. These include: engineering science (for risk analysis; structural resistance etc.); organisation sciences and sociology; geosciences and geography; and risk communication. It will present the progress made in ERRA-NATECH on the development of a new risk Analysis Method. This risk analysis method is supposed to answer the following emerging risk issue: how to cope Industry development in areas exposed to natural hazards or disasters: higher hazard potential, higher frequency of accidents.


A training set of 90 malignant cases (positives) and 61 non-malignant cases (negatives) was used to determine statistics for five parameters based on white blood cell analysis. The statistics used were thresholds, differences between the positive and negative means, and the weighted correlation matrix. Three decision methods using these statistics were then applied to a test set of 90 positives and 60 negatives. The percentage of correct decisions ranged from 98.67 per cent for parameter 3. The best result using only parameters capable of recognition by an automated apparatus was 94.00 per cent.


Window technique is one of the simplest methods to design finite impulse response (FIR) filters. It uses special functions to truncate an infinite sequence to a finite one. In this paper, we propose window techniques based on integer sequences. The striking feature of the proposed work is that it overcomes all the problems posed by floating point numbers and inaccuracy, as the sequences are made of only integers. Some of these integer window sequences, yield sharp transition, while some of them result in zero ripple in passband and stopband.


OBJECTIVE
There is evidence that major depression increases the risk for dementia, but there is conflicting evidence as to whether depression may accelerate cognitive decline in dementia. The authors tested the hypothesis that decline in cognitive function over time is more pronounced in patients with dementia with comorbid depression, when compared with patients with dementia without depression history.

DESIGN
Prospective, longitudinal cohort study of aging.

SETTING
Nursing home.

PARTICIPANTS
Three hundred thirteen elderly nursing home residents (mean age at baseline: 86.99 years, standard deviation = 6.7; 83.1% women). At baseline, 192 residents were diagnosed with dementia, and another 27 developed dementia during follow-up. Thirty residents suffered from major depression at any point during the study, and 48 residents had a history of depression.

MEASUREMENTS
The authors measured cognitive decline using change in Mini-Mental State Examination (MMSE) scores over up to 36 months. The authors calculated multilevel regression models to estimate the effects of age, gender, education, dementia status, depression, depression history, and an interaction between dementia and depression, on change in MMSE scores over time.

RESULTS
Beyond the effects of age, gender, and education, residents showed steeper cognitive decline in the presence of dementia (β = -13.69, standard error = 1.38) and depression (β = -4.16, SE = 1.2), which was further accelerated by the presence of both depression and dementia (β = -2.72, SE = 0.65).

CONCLUSIONS
In dementia, the presence of depression corresponds to accelerated cognitive decline beyond gender and level of education, suggesting a unique influence of depression on the rate of cognitive decline in dementia.


Urban traffic planning has a fundamental role in our society, for it improves the use of traffic roads and optimizes the flow of both vehicles and pedestrians. Nowadays, different mathematical models exist to facilitate this activity. They are virtually built and computer simulated and are basically categorized in two groups: macro and micro-simulation models. The first presents traffic as flow values whereas the second specifies traffic by representing each vehicle. The primary goal of this work was to develop a singular traffic micro-simulation tool using a desktop Virtual Reality (VR) interface and improved steering behaviours. This tool will serve as a basis for the future development of a transit simulator with a distributed architecture.


Fenofibrate, a drug of fibrate class, is mainly used to reduce cholesterol levels in patients at risk of cardiovascular disease. However, bioavailability of fenofibrate is often low and unpredictably due to its poor solubility. Microparticle entrapped micelles (MEM) technology is a novel method of incorporating surfactants in solid dosage form for improving in vitro and in vivo performance of poorly water soluble drugs. Increasing the fenofibrate solubility by MEM technology has not been reported in the literature. In this study, the formulation of fenofibrate modified by MEM technology (FB-MEM) was studied. The FB-MEM was then filled in the hard capsules with high dissolution profile. Fenofibrate was solubilized in various surfactants (tween 80, tween 60, Kolliphor P407, Acrysol K140, Gelucire 44/14) at different concentration of 0.5; 1; 3 and 5 % at cloud point temperature; the dispersion was dried to obtain solid product. The FE-MEM with highest solubility was then characterized by DSC and FTIR spectra. By using Acrysol K140 as surfactant, the FEMEM solubility was enhanced up to 644 mg fenofibrate / 1 g surfactant. DSC diagram and FTIR spectra showed that there was no chemical interaction between fenofibrate and Acrysol K140. The high solubility of FE-MEM was thus possibly due to low melting point of this mixture and small size of FE-MEM. By using Primellose as disintegration excipient, hard capsule containing 200 mg of fenofibrate (FE-MEM) showed an equivalent dissolution profile with Lipanthyl (the similariry factor f2 = 53). Keyword: fenofibrate, microparticle entrapped micelles (MEM), hard capsule, high dissolution profile.


For the last decade, the fabrication of ordered structures of phage has been of great interest as a means of utilizing the outstanding biochemical properties of phage in developing useful materials. Combined with other organic/inorganic substances, it has been demonstrated that phage is a superior building block for fabricating various functional devices, such as the electrode in lithium-ion batteries, photovoltaic cells, sensors, and cell-culture supports. Although previous research has expanded the utility of phage when combined with genetic engineering, most improvements in device functionality have relied upon increases in efficiency owing to the compact, more densely packable unit size of phage rather than on the unique properties of the ordered nanostructures themselves. Recently, self-templating methods, which control both ther- modynamic and kinetic factors during the deposition process, have opened up new routes to exploiting the ordered structural properties of hierarchically organized phage architectures. In addition, ordered phage films have exhibited unexpected functional properties, such as structural color and optical filtering. Structural colors or optical filtering from phage films can be used for optical phage-based sensors, which combine the structural properties of phage with target-specific binding motifs on the phage-coat proteins. This self-templating method may contribute not only to practical applications, but also provide insight into the fundamental study of biomacro- molecule assembly in in vivo systems under complicated and dynamic conditions. DOI 10.1002/tcr.201200012


This paper describes the magnetic properties, recording performance and corrosion resistance of sputtered CoCr alloy films and CoCrTa alloy films. The saturation magnetization of CoCr was 525 emu/cc and not affected by substitution of a small amount of Ta. CoCrTa films exhibit greater coercive force values than CoCr films. The maximum coercive force of CoCrTa was 1400 Oe at a thickness of 400A, whereas at a similar thickness the coercive force of CoCr was 900 Oe. The coercive force decreases linearly with temperature (25°C. to 125°C.) at a rate of 3.16 Oe/°C. for CoCrTa and 1.87 Oe/°C. for CoCr. Longitudinal recording performance at -3 dB signal level was 8386 flux reversals/cm (21,300 fci) and 11,063 flux reversals/cm (28,100 fci) for CoCr and CoCrTa respectively. The alloys exhibited corrosion resistance at 80% relative humidity and 65° C. for a two-week period equivalent to at least six years under ambient disc drive conditions.


The aim of the present study was to study the effects of cycling and pure concentric and pure eccentric high-intensity interval exercise (HIIE) on skeletal muscle (i.e., vastus lateralis) and cerebral oxygenation. Twelve healthy males (n = 12, age 26 ± 1 yr, body mass 78 ± 2 kg, height 176 ± 2 cm, body fat 17 ± 1% of body mass) performed, in a random order, cycling exercise and isokinetic concentric and eccentric exercise. The isokinetic exercises were performed on each randomly selected leg. The muscle and the cerebral oxygenation were assessed by measuring oxyhemoglobin, deoxyhemoglobin, total hemoglobin, and tissue saturation index. During the cycling exercise, participants performed seven sets of seven seconds maximal intensity using a load equal to 7.5% of their body mass while, during isokinetic concentric and eccentric exercise, they were performed seven sets of five maximal muscle contractions. In all conditions, a 15 s rest was adopted between sets. The cycling HIIE caused greater fatigue (i.e., greater decline in fatigue index) compared to pure concentric and pure eccentric isokinetic exercise. Muscle oxygenation was significantly reduced during HIIE in the three exercise modes, with no difference between them. Cerebral oxygenation was affected only marginally during cycling exercise, while no difference was observed between conditions. It is concluded that a greater volume of either concentric or eccentric isokinetic maximal intensity exercise is needed to cause exhaustion which, in turn, may cause greater alterations in skeletal muscle and cerebral oxygenation.


Tool wear plays an important role in cutting process research. It affects the quality of machined surface and cutting parameter to a great extent, such as cutting force, cutting temperature and cutting quiver. In order to predict tool wear in hard cutting process by using FEM method, the character of tool wear during cutting process is presented firstly, and Usui's tool wear rate model is introduced. Then the FEM model for steady state cutting process using Abaqus is established. FEM model describes the workpiece material characteristic accurately for the process of PCBN tool cutting GCr15 by adoptiving Johnson-Cook constitutive model. Simulation results of steady cutting process offer foundation to simulate tool wear.


The effects of an addition of polyethylene functionalized with ricinol-2-oxazoline methyl maleate (PE-g-MRO), acting as compatibilizer, on the morphology, phase transitions and selected mechanical properties of the blendsconsisted of thermoplastic polyester elastomer/polyamide 6 (TPE-E/ PA6) prepared by reactive extrusion were investigated. Thermodynamic parameters (glass transition temperature, temperature and enthalpy of crystallization and melting transitions of the blends versus their compositions) were determined using differential scanning calorimetry (DSC, Table 2, Figs. 1-3). Morphology of TPE-E/PE-g-MRO/PA6 blends has been characterized by scanning electron microscopy (SEM). Furthermore the static tensile and flexural properties as well as Charpy impact strength and heat distortion temperature (Table 4) were tested. It has been found that the blends investigated showed compatible heterogenic structure (Figs. 4, 5) formed during reactive extrusion as a result of the reactions of functional groups of TPE-E, PA 6 or PE-g-MRO. The structure stabilizes on the microphase level what let obtain high impact strength and excellent mechanical properties of the blends (Table 4, Fig. 6). SEM results are in agreement with DSC results as well as with the results of formic acid extraction (Table 3) and suggest the formation of new TPE-E-block-PA6 copolymers, increasing the interfacial interactions. The results confirm the effective action of PE-g-MRO as a compatibilizer for TPE-E/ PA6 blends causing the improvement of majority of functional properties, mainly impact strength, of these blends.


Quality is the hallmark of a competitive product. It is necessary to use inspection stations to check product quality and process performance. In this paper, the authors are concerned with the problem of location of inspection stations in a multistage manufacturing system. The authors present two stochastic search algorithms for solving this problem, one based on simulated annealing and the other on genetic algorithms. These algorithms are developed to determine the location of inspection stations resulting in a minimum expected total cost in a multistage manufacturing system. The total cost includes inspection, processing and scrapping cost at each stage of the production process. A penalty cost is also included in it to account for a defective item which is not detected by the inspection scheme. A set of test examples are solved using these algorithms. The authors also compare performance of these two algorithms.


Apoptin, a protein expressed by chicken anemia virus, is found predominantly in the cytoplas min normal cells, whereas it localizes in the nucleus in transformed and malignant cells. However, the mechanisms that regulate the different subcellular localization of Apoptin in normal and tumor cells have not been fully clarified. In this work, a putative nuclear export signal (NES) in Apoptin was predicted. It was testified that the putative NES (pNES) of Apoptin was not a functional NES, but actually acted as a cytoplasmic retention signal. Deletion of the pNES led to the nuclear accumulation of Apoptin in normal cells. In addition,when a strong nuclear localization signal was introduced into Apoptin, it exclusively translocated to the nucleus in normal cells. These observations indicated that the cytoplasmic localization of Apoptin in normal cells results from the balance between cytoplasmic retention and nuclear import. On the other hand, the pNES was also proved to be necessary for Apoptin multimerization. Mutants lacking the pNES did not form obviously visible globular aggregates in normal or tumor cells.


Fatigue tests were made on some 1.375-inch-diameter and 0.300-inch diameter specimens of a 17S-T aluminum alloy rod. One test of a large specimen was run continuously to failure at a maximum stress of 22,000 pounds per square inch. In two other tests of large specimens, thin surface layers were removed periodically until failure occurred. The same nominal maximum stress of 22,000 pounds per square inch was used throughout the two tests and the load on the fatigue machine was lowered accordingly after the removal of each surface layer. As each test progressed the stress in the metal of the final surface area therefore was increased after the removal of each surface layer. Because of the stresses used, this metal was overstressed, that is, stressed above its endurance limit. All the remaining specimens were subjected to similar over- stressing conditions but no metal was removed and a low initial stress was increased periodically to a final maximum value of 22,000 pounds per square inch as each test progressed. It was found that the fatigue resistance of 17S-T aluminum alloy can be increased by moderate overstressing. Apparently the increase in fatigue lift obtained in the tests of specimens from which layers were removed was the result of overstressing rather than from the removal of damaged surface layers.


This study looks at the performance of livestock production in Uruguay and Paraguay, analyzing two situations with different implications for development: the displacement of livestock by soybean production as occurred in Uruguay and in the Eastern region of Paraguay, and the expansion of the agricultural frontier in western Paraguay through deforestation. In the case of Uruguay, and despite being displaced to lower-quality land, the livestock sector has seen a historical increase in output and productivity between 2002 and 2006 as the result of rapid growth in beef and milk production and a reduction of sheep stocks to historical lows. This growth was driven by changes in nutrition, mostly due to an increase in the area under cultivated pasture during the second half of the 1990s, the use of grain and supplements associated to dairy production, and more recently, by intensive fattening of cattle. Improved nutrition resulted in a reduction in the slaughter age of steers, an increase in the offtake rate and a larger contribution of dairy to total output. In the case of Paraguay, beef production more than doubled between 2005 and 2016, driven by productivity growth which increased by 70 percent during this period. The expansion of soybean production in the Eastern region after 2006 displaced livestock to the Western Region of Chaco. In this new environment, the adoption of high yielding varieties of tropical pastures together with improved animal genetics were the main factors behind increased productivity. Despite these positive developments, livestock sectors in Uruguay and Paraguay still face major challenges to sustain growth in the future. In the case of Uruguay, the challenge is to accelerate and sustain TFP growth, which stagnated again after 2006. For Paraguay, challenges for future development are those related to the environment, as future expansion of production will continue to take place into forest land in the Chaco region. Although the introduction of cultivated pastures has increased productivity and reduced emissions per unit of output both in Uruguay and Paraguay, in the case of Paraguay, increased production, a growing animal stock and deforestation will continue to increase GHG emissions and will require greater control in the use of natural resources and new technological developments to increase environmental efficiency of livestock production.


This research was based on the conceptual framework that students' low mathematics achievement in school is related to their poor study habits. Thus, the intervention titled Mathematics Self-Regulated Learning Program aimed to help selected children from Southeast Asia (the Philippines) improve their Mathematics achievement, Mathematics self-regulated learning, and Mathematics school grade. This research focused on the following difference scores: 1) Mathematics achievement, Mathematics self-regulated learning, and Mathematics school grade between experimental and control groups (N = 60); and 2) Mathematics achievement, Mathematics self-regulated learning, and Mathematics school grade between younger and older groups (N = 60). The main result supports self-regulated learning theory which states that when students are given opportunities to self-regulate and explicitly taught of self-regulated learning strategies, academic achievement is more likely to be positively affected. The study confirms that students as active agents of their behaviors can be trained to be responsible learners and thus acquire the goal of life-long education which is learning not just what to learn but more importantly how to learn. ********** Why do some people approach learning tasks eagerly while others avoid them or work half-heartedly? Why do some seek and enjoy learning, while others are afraid to learn? Educators and parents long have been plagued by the problem of students' low achievement in school. Many have had the frustrating experience of watching a child undermine his or her chances for a good performance simply by not trying. A student who performs poorly as a consequence of not studying or not completing assignments is usually perceived by his teachers as a hopeless case. Many students who encounter achievement problems in school frequently warrant the concerned scrutiny of teachers and parents alike. They are victims of pre-judgment that they can do no better. The researcher in her three years of teaching in the elementary grades encountered colleagues and parents who have lost hope in teaching children who were branded as "lazy"; "just don't like to try"; and "take for granted studyi3ng." This experience served as a challenge to the researcher. She likes to contend that children can be taught of self-regulated learning skills and thus improve their performance in school. Teachers have the responsibility to teach students not just what to learn but more importantly how to learn. Teaching students of self-regulated learning strategies is reflective of the life-long goal of education which is teaching students the will as well as the skill in learning (Pintrich & de Groot, 1990). As the old aphorism would say "... teach a man how to fish and you have fed him for life." This study helped students realize that it is possible for them to generate and direct their own learning experiences rather than act in response to external controls. That they are self-initiators who can exercise personal choice and control of the methods needed to attain the learning goals they have set for themselves. That they function as origins of their own behavior rather than pawns controlled by outside forces (de Charms, 1987). In this way, their fullest potential will be developed. Teachers can use self-regulated learning strategies on their students and therefore change the traditional perception of teachers that some students just cannot learn what they teach. The researcher hopes that the teachers will internalize within themselves that students come to school to learn and should be taught how to learn. The teacher should contribute to the development of student's positive self-image, rather than to the establishment of a self-defeating behavior. Research indicated that students' low achievement in school is related to their poor study habits. Figure 1 illustrates that training the students to be self-regulated learners through the Self-Regulated Learning Program (SRLP) will help them improve their Mathematics achievement and study habits. …


In the present study, anti-Avian influenza virus H9N2 activity of aqueous extracts (5, 10, 15, 20, 25%) of Zingiber officinalis and Allium sativum was evaluated. Embryo-toxicity was evaluated by histopathological scoring of Chorio-allantoic membrane of chick embryos. Cytotoxicity of extracts was determined by MTT assay on Vero cells. Aqueous extract of ginger had antiviral activity at 10, 15, 20 and 25% while garlic had activity at 15, 20 and 25%. Histopathological scoring of chorio-allantoic membrane for aqueous extracts (5, 10, 15, 20, 25%) of ginger (0.66±0.57, 1.33±0.57, 1.66±0.57, 2.66±0.57, 3.66±0.57, respectively) and garlic (1.00±0.00, 1.33±0.57, 2.00±0.00, 2.33±0.57, 3.66±0.57, respectively) was concentration dependant. MTT assay revealed cytotoxicity of both plants was also concentration dependent. Extracts of ginger (5, 10, 15, 20, 25%) had lower cytotoxicity (71, 59, 28, 22, 0 % cell survival, respectively) as compared to garlic (61, 36. 20, 11, 3% cell survival, respectively). Overall results revealed that concentration of aqueous extract of ginger (10%), showing antiviral activity against H9N2, was less toxic to vero cells (> 50% cell survival). It is insinuated that ginger may have anti- Avian influenza virus H9N2 potential and its active compounds needs further investigations.


Abstract : Patients with locally advanced breast cancer, which represents less than 5% of annually diagnosed breast cancer cases, are a very heterogeneous group of patients. The optimal management of these patients remains controversial. Several randomized and nonrandomized clinical trials demonstrate a benefit in the use of chemotherapy combined with local treatment (surgery and/or radiation therapy) for these patients with prolongation of both disease free and overall survival. Given the ability of radiation therapy to control local disease and the failure of conventional chemotherapy to provide long lasting control of distant disease, combining paclitaxel with radiation therapy seems worthy of investigation. We have shown in tissue culture a supraadditive interaction between this drug and radiation. In our clinical trial, patients received six weekly 3-hour infusions of paclitaxel during preoperative radiation therapy, followed by modified radical mastectomy when possible. All patients received adjuvant CAF chemotherapy. To date, we have enrolled six patients; three patients at 25 mg/M2, and three patients at 33 mg/M2 paclitaxel. No unexpected adverse reactions were observed in the first six patients. Three of six patients obtained a clinical complete response prior to surgery, two patients had a partial response, and one patient progressed. All patients had a mastectomy with a pathologic response remarkable for residual microscopic disease in those patients who had clinical complete responses. Two patients are dead of disease, three patients are free of disease, and one is alive, but clinical status is unknown. Pharmacokinetic studies revealed levels of drug present in serum 4-72 hours after infusion in the radiation sensitizing range observed in tissue culture. Needle aspirations of tumors during chemoradiation were obtained.


Rough terrain autonomous navigation continues to pose a challenge to the robotics community. Robust navigation by a mobile robot depends not only on the individual performance of perception and planning systems, but on how well these systems are coupled. When traversing complex unstructured terrain, this coupling (in the form of a cost function) has a large impact on robot behavior and performance, necessitating a robust design. This paper explores the application of Learning from Demonstration to this task for the Crusher autonomous navigation platform. Using expert examples of desired navigation behavior, mappings from both online and offline perceptual data to planning costs are learned. Challenges in adapting existing techniques to complex online planning systems and imperfect demonstration are addressed, along with additional practical considerations. The benefits to autonomous performance of this approach are examined, as well as the decrease in necessary designer effort. Experimental results are presented from autonomous traverses through complex natural environments.


Aim To examine system characteristics associated with variations in unplanned admission rates in those aged 85+. Design Mixed methods. Setting Primary care trusts in England were ranked according to changes in admission rates for people aged 85+ between 2007 and 2009, and study sites selected from each end of the distribution: three 'improving' sites where rates had declined by more than 4% and three 'deteriorating' sites where rates had increased by more than 20%. Each site comprised an acute hospital trust, its linked primary care trust/clinical commissioning group, the provider of community health services and adult social care. Participants A total of 142 representatives from these organisations were interviewed to understand how policies had been developed and implemented. McKinsey's 7S framework was used as a structure for investigation and analysis. Results In general, improving sites provided more evidence of comprehensive system focused strategies backed by strong leadership, enabling the development and implementation of policies and procedures to avoid unnecessary admissions of older people. In these sites, primary and intermediate care services appeared more comprehensive and better integrated with other parts of the system, and policies in emergency departments were more focused on providing alternatives to admission. Conclusions Health and social care communities which have attenuated admissions of people aged 85+ prioritised developing a shared vision and strategy, with sustained implementation of a suite of interventions.


This article quantifies the effects of increasing global geopolitical uncertainty on the size of migration flows to Western Europe. Uncertainty is measured by the number of victims of terrorist attacks worldwide. The effect on migration flows is quantified through the estimation of vector autoregressive models on a panel of 15 European countries and on France, thanks to an original migration dataset. The estimations suggest that the flows of permanent migrants are generally reduced by global terrorism. In particular, the increase in uncertainty that followed the attacks of September 11, 2001, caused an 8% drop in flows to Europe and a 19% drop in flows to France. The effect of global uncertainty on the flow of asylum seekers depends on the country: on average in Europe, asylum applications increase with terrorism, but for France, they decrease with terrorism. This difference can be explained by the geographical position and border control policies of France.


Monolayers presenting methyl-terminated (hydrophobic) and hydroxyl-terminated (hydrophilic) surfaces on silica have been studied by molecular dynamics simulation and the effects of hydrogen bonding, chain length, and chain mixing on the frictional properties determined. The hydroxyl-terminated monolayers were found to show large adhesion zones as a result of strong interfacial interlayer hydrogen bonds; the interfacial sliding forces observed in the hydroxyl-terminated monolayers being one order of magnitude higher than the interfacial forces for the hydrophobic surfaces at the characteristic point of zero-load. Mixed hydroxyl- and methyl-terminated monolayers of equal length were found to exhibit intermediate shear stress values between those observed for pure monolayers, with the magnitude of the shear stress depending on the surface content of the hydroxyl-terminated chains. For mixed monolayers of unequal chain lengths, at high loads a maximum in the magnitude of the shear stress as a function of the length of the methyl-terminated chain was observed due to the creation of a buffer zone between the hydroxyl-terminated chains that produces strong hydrogen-bonding interactions. The effect of a constant normal load or constant separation simulation ensemble on the results has also been studied and in general found to have minimal influence on the observed behavior, although some differences are observed for the shear stress at intermediate normal loads due to the formation of stronger hydrogen bond networks at constant load compared to constant separation.


Abstract A quantitative determination of Fe3+/ΣFe ratios using the electron microprobe is presented for glasses. The measurements are based on the shift of the Fe-Lα peak position between Fe3+ and Fe2+, resulting from differences in self-absorption. We present new calibration curves for glasses with Fe contents as low as 2 wt.% Fe. This method was used for glasses from a metasomatized spinel lherzolite (Massif Central, France) in which highly vesicular glass associated with secondary minerals occurs in reaction pockets around corroded Cr-spinels. The glass was found to be oxidized homogeneously with Fe3+/ΣFe ≈ 0.70 (measured with an uncertainty of 0.06), in contrast with the value of ~0.15 that would correspond to the former melt under fO₂ conditions inferred from secondary minerals. The glass oxidation probably results from the dissociation of the melt-water content under degassing, prior to local hematite depositions (spinel rims and crack fillings).


Introduction: The World Health Organisation (WHO) and the International Pharmaceutical Federation (FIP) recommend emphasising clinical education within a balanced pharmacy curriculum. During the summer of 2016 the University of Graz (KFU), sponsored an elective English language teaching event on clinical pharmacy for undergraduate pharmacy students. This project aimed to evaluate the views, experiences and attitudes of Austrian students taking part in this clinical pharmacy teaching event. Methods: A mixed method study using a quantitative questionnaire survey followed by qualitative semi-structured, one-to-one telephone interviews. Results: The response rate to the questionnaire and telephone interview study was 67% (n=20) and 30% (n=6) respectively. Students were satisfied with the teaching event (very good: 90% (n=18); good: (10% (n=2). They felt inspired to learn more about clinical pharmacy in the future (100% (n=20)). Main themes included opportunity, relevance and the desire to shape their own future profession. Conclusion: Students at KFU welcomed the opportunity to learn about clinical pharmacy at undergraduate level.


Rationale: Nitric oxide (NO) bioavailability is reduced in the setting of heart failure. Nitrite (NO2) is a critically important NO intermediate that is metabolized to NO during pathological states. We have previously demonstrated that sodium nitrite ameliorates acute myocardial ischemia/reperfusion injury. Objective: No evidence exists as to whether increasing NO bioavailability via nitrite therapy attenuates heart failure severity after pressure-overload–induced hypertrophy. Methods and Results: Serum from patients with heart failure exhibited significantly decreased nitrosothiol and cGMP levels. Transverse aortic constriction was performed in mice at 10 to 12 weeks. Sodium nitrite (50 mg/L) or saline vehicle was administered daily in the drinking water postoperative from day 1 for 9 weeks. Echocardiography was performed at baseline and at 1, 3, 6, and 9 weeks after transverse aortic constriction to assess left ventricular dimensions and ejection fraction. We observed increased cardiac nitrite, nitrosothiol, and cGMP levels in mice treated with nitrite. Sodium nitrite preserved left ventricular ejection fraction and improved left ventricular dimensions at 9 weeks (P<0.001 versus vehicle). In addition, circulating and cardiac brain natriuretic peptide levels were attenuated in mice receiving nitrite (P<0.05 versus vehicle). Western blot analyses revealed upregulation of Akt-endothelial nitric oxide-nitric oxide-cGMP-GS3K&bgr; signaling early in the progression of hypertrophy and heart failure. Conclusions: These results support the emerging concept that nitrite therapy may be a viable clinical option for increasing NO levels and may have a practical clinical use in the treatment of heart failure.


Two questionnaires and a survey conducted by Dr. Corey Gilbert in his Human Sexuality course taught at two private, Christian schools provided the data for this research. Research was conducted using statistical correlation between sexual experiences against social and environmental factors, including but not limited to: parental influence, sexual education in school, comfort talking with peers, and age of sexual exposure. The quantitative cross correlation revealed many statistically significant correlations including student conservativeness with sexual behaviors, parental influence on the child's sexual behavior, and a correlation between the main source of sexual information and number of risky sexual experiences. The qualitative data was derived from questions about the Human Sexuality course itself, and revealed students in these courses, not dependent on their sexual experiences or self-labeled conservativeness, are eager to discuss their feelings and experiences in the effort to better understand healthy sexuality. There appears to be something missing in our present day system of teaching sexuality, and it is evident in the mentality and behaviors of our current college generation


Objective: To assess improvement in predictive performance of Global Registry of Acute Coronary Events risk score (GRS) by addition of a glucose matrix. Methods: 1,056 acute coronary syndrome (ACS) survivors without known diabetes had pre-discharge fasting (FPG) and 2-h post-load plasma glucose (2h-PG) measured. GRS was calculated. Major adverse cardiac events (MACE; death and non-fatal myocardial infarction) were recorded during follow-up. Cox proportional hazard regression predicted event-free survival. Likelihood ratio test, Akaike's information criteria, continuous net reclassification index (NRI>0), and integrated discrimination improvement (IDI) were used to test the additional prognostic value of glycaemic indices over GRS. Results: During a median follow-up of 36.5 months, 211 MACEs (20.0%), 96 deaths (9.1%), and 115 non-fatal re-infarctions (10.9%), occurred. 2h-PG, but not FPG, independently predicted MACE-free survival at all time points (HR 1.08, 95% CI 1.03–1.13, p = 0.002, at 3 years). Risk of MACE increased by 8–11% with every 1 mmol/L rise in 2h-PG. 2h-PG significantly improved the prognostic models containing GRS. Models containing GRS and 2h-PG yielded lowest corrected Akaike's information criteria compared to that with only GRS. 2h-PG, but not FPG, improved NRI>0 (NRI>0 0.169, p = 0.028 at 3 years) and IDI (IDI of 0.66%, p = 0.018 at 3 years) significantly at all time points during the follow-up. Conclusions: 2h-PG, but not FPG, improves performance of GRS-containing models in predicting post-ACS prognosis in the short to medium term.


Coffee consumers differ in the importance and value they place in high-quality coffee. Focus groups revealed that coffee choices are influenced by habit, familiarity, meaning and significance, price, and one's identity as it relates to coffee. Emotional consumer tests were performed with three different qualities of coffee, leading to the identification of four consumer clusters that varied in their degree of "involvement" with coffee. "Typical coffee drinkers" and "uninterested coffee drinkers" did not care strongly about coffee, while "coffee lovers" loved all coffee and "coffee snobs" were choosey and discriminative about their coffee. Self-identified coffee connoisseurs were no more likely to consume high-quality coffee than non-connoisseurs, suggesting that self-selecting an identity may say more about consumers wish to convey versus their true consumption habits. The most important emotional qualities consumers seek in their coffee relate to gratification, calming, focusing, the absence of disgust, and general positive


Intestinal barrier dysfunction remains a critical problem in patients with intracerebral hemorrhage (ICH) and is associated with poor prognosis. Ghrelin, a brain-gut peptide, has been shown to exert protection in animal models of gastrointestinal injury. However, the effect of ghrelin on intestinal barrier dysfunction post-ICH and its possible underlying mechanisms are still unknown. This study was designed to investigate whether ghrelin administration attenuates intestinal barrier dysfunction in experimental ICH using an intrastriatal autologous blood infusion mouse model. Our data showed that treatment with ghrelin markedly attenuated intestinal mucosal injury at both histomorphometric and ultrastructural levels post-ICH. Ghrelin reduced ICH-induced intestinal permeability according to fluorescein isothiocyanate conjugated-dextran (FITC-D) and Evans blue extravasation assays. Concomitantly, the intestinal tight junction-related protein markers, Zonula occludens-1 (ZO-1) and claudin-5 were upregulated by ghrelin post-ICH. Additionally, ghrelin reduced intestinal intercellular adhesion molecule-1 (ICAM-1) expression at the mRNA and protein levels following ICH. Furthermore, ghrelin suppressed the translocation of intestinal endotoxin post-ICH. These changes were accompanied by improved survival rates and an attenuation of body weight loss post-ICH. In conclusion, our results suggest that ghrelin reduced intestinal barrier dysfunction, thereby reducing mortality and weight loss, indicating that ghrelin is a potential therapeutic agent in ICH-induced intestinal barrier dysfunction therapy.


Very few areas of medical science have experienced more rapid development of new and beneficial treatment approaches during the past two decades than the disciplines required for total care of patients with major thermal injury. The introduction of a multidisciplinary scientific approach to the diagnosis and treatment of very complex postburn complications has been primarily responsible for the major advances in clinical care. This report highlights those areas of advancement which have been most significant in upgrading current inpatient therapy.


A time-resolved Raman spectrometer is demonstrated based on a $256\times 8$ single-photon avalanche diodes fabricated in CMOS technology (CMOS SPAD) line sensor and a 573-nm fiber-coupled diamond Raman laser delivering pulses with duration below 100-ps full-width at half-maximum (FWHM). The collected backscattered light from the sample is dispersed on the line sensor using a custom volume holographic grating having 1800 lines/mm. Efficient fluorescence rejection in the Raman measurements is achieved due to a combination of time gating on sub-100-ps time scale and a 573-nm excitation wavelength. To demonstrate the performance of the spectrometer, fluorescent oil samples were measured. For organic sesame seed oil having a continuous wave (CW) mode fluorescence-to-Raman ratio of 10.5 and a fluorescence lifetime of 2.7 ns, a signal-to-distortion value of 76.2 was achieved. For roasted sesame seed oil having a CW mode fluorescence-to-Raman ratio of 82 and a fluorescence lifetime of 2.2 ns, a signal-to-distortion value of 28.2 was achieved. In both cases, the fluorescence-to-Raman ratio was reduced by a factor of 24–25 owing to time gating. For organic oil, spectral distortion was dominated by dark counts, while for the more fluorescent roasted oil, the main source of spectral distortion was timing skew of the sensor. With the presented postprocessing techniques, the level of distortion could be reduced by 88%–89% for both samples. Compared with common 532-nm excitation, approximately 73% lower fluorescence-to-Raman ratio was observed for 573-nm excitation when analyzing the organic sesame seed oil.


Characterizing the intermediate phenotypes, such as gene expression, that mediate genetic effects on complex diseases is a fundamental problem in human genetics. Existing methods utilize genotypic data and summary statistics to identify putative disease genes, but cannot distinguish pleiotropy from causal mediation and are limited by overly strong assumptions about the data. To overcome these limitations, we develop Causal Multivariate Mediation within Extended Linkage disequilibrium (CaMMEL), a novel Bayesian inference framework to jointly model multiple mediated and unmediated effects relying only on summary statistics. We show in simulation that CaMMEL accurately distinguishes between mediating and pleiotropic genes unlike existing methods. We applied CaMMEL to Alzheimer's disease (AD) and found 206 causal genes in sub-threshold loci (p < 10−4). We prioritized 21 genes which mediate at least 5% of local genetic variance, disrupting innate immune pathways in AD.


Abstract:This article explores the large Scandinavian trade in cheap and colorful Chinese silk textiles between 1731 and 1761. Most pieces brought from Canton (Guangzhou) to Denmark and Sweden were monochrome, with discreet designs and patterns. What stood out was the wide color assortment, shades named with a nomenclature shared by the European East India companies. Changing quantities of different shades of red and blue silks reveal shifting Scandinavian consumer demands. The lack of new colors in the assortment of cheap and cheerful Chinese silks suggests, however, that Canton only played a limited role as a fashion leader.


Letter from F. A. Mood to Hon. J. D. Giddings. Mood explains that his letter encloses original and duplicate copies of contracts made by the Trustees of Southwestern University regarding Southwestern Life Insurance Company. He asks Giddings to sign and forward the contract at his earliest convenience. Mood then describes how Southwestern has experienced an encouraging influx of students at Christmas and expects more by 21 February, the beginning of the spring term. The university enjoys a high level of scholarship, and Mood hopes for continued blessings for the school.


: The studies carried during ships navigation covered some intrinsic factors (levels of noise, vibration, microclimate, air components, concentration of polymers, electrostatic fields, and others) of the ship and such extrinsic environmental factors as climate of the navigation area, temperature, ambient air moisture, wind force and direction. The studies proved strong correlation between hygienic parameters in the ship and its type and destination, length of service, climate of the navigation area, that is assumed to be a criteria for evaluation of work conditions at the ship.


OBJECTIVE Recent advances in optics and miniaturization have enabled the development of a growing number of minimally invasive procedures, yet innovative training methods for the use of these techniques remain lacking. Conventional teaching models, including cadavers and physical trainers as well as virtual reality platforms, are often expensive and ineffective. Newly developed 3D printing technologies can recreate patient-specific anatomy, but the stiffness of the materials limits fidelity to real-life surgical situations. Hollywood special effects techniques can create ultrarealistic features, including lifelike tactile properties, to enhance accuracy and effectiveness of the surgical models. The authors created a highly realistic model of a pediatric patient with hydrocephalus via a unique combination of 3D printing and special effects techniques and validated the use of this model in training neurosurgery fellows and residents to perform endoscopic third ventriculostomy (ETV), an effective minimally invasive method increasingly used in treating hydrocephalus. METHODS A full-scale reproduction of the head of a 14-year-old adolescent patient with hydrocephalus, including external physical details and internal neuroanatomy, was developed via a unique collaboration of neurosurgeons, simulation engineers, and a group of special effects experts. The model contains "plug-and-play" replaceable components for repetitive practice. The appearance of the training model (face validity) and the reproducibility of the ETV training procedure (content validity) were assessed by neurosurgery fellows and residents of different experience levels based on a 14-item Likert-like questionnaire. The usefulness of the training model for evaluating the performance of the trainees at different levels of experience (construct validity) was measured by blinded observers using the Objective Structured Assessment of Technical Skills (OSATS) scale for the performance of ETV. RESULTS A combination of 3D printing technology and casting processes led to the creation of realistic surgical models that include high-fidelity reproductions of the anatomical features of hydrocephalus and allow for the performance of ETV for training purposes. The models reproduced the pulsations of the basilar artery, ventricles, and cerebrospinal fluid (CSF), thus simulating the experience of performing ETV on an actual patient. The results of the 14-item questionnaire showed limited variability among participants' scores, and the neurosurgery fellows and residents gave the models consistently high ratings for face and content validity. The mean score for the content validity questions (4.88) was higher than the mean score for face validity (4.69) (p = 0.03). On construct validity scores, the blinded observers rated performance of fellows significantly higher than that of residents, indicating that the model provided a means to distinguish between novice and expert surgical skills. CONCLUSIONS A plug-and-play lifelike ETV training model was developed through a combination of 3D printing and special effects techniques, providing both anatomical and haptic accuracy. Such simulators offer opportunities to accelerate the development of expertise with respect to new and novel procedures as well as iterate new surgical approaches and innovations, thus allowing novice neurosurgeons to gain valuable experience in surgical techniques without exposing patients to risk of harm.


We study the power of the bounded-width consistency algorithm in the context of the fixed-template Promise Constraint Satisfaction Problem (PCSP). Our main technical finding is that the template of every PCSP that is solvable in bounded width satisfies a certain structural condition implying that its algebraic closure-properties include weak near unanimity polymorphisms of all large arities. While this parallels the standard (non-promise) CSP theory, the method of proof is quite different and applies even to the regime of sublinear width. We also show that, in contrast with the CSP world, the presence of weak near unanimity polymorphisms of all large arities does not guarantee solvability in bounded width. The separating example is even solvable in the second level of the Sherali-Adams (SA) hierarchy of linear programming relaxations. This shows that, unlike for CSPs, linear programming can be stronger than bounded width. A direct application of these methods also show that the problem of $q$-coloring $p$-colorable graphs is not solvable in bounded or even sublinear width, for any two constants $p$ and $q$ such that $3 \leq p \leq q$. Turning to algorithms, we note that Wigderson's algorithm for $O(\sqrt{n})$-coloring $3$-colorable graphs with $n$ vertices is implementable in width $4$. Indeed, by generalizing the method we see that, for any $\epsilon>0$ smaller than $1/2$, the optimal width for solving the problem of $O(n^\epsilon)$-coloring $3$-colorable graphs with $n$ vertices lies between $n^{1-3\epsilon}$ and $n^{1-2\epsilon}$. The upper bound gives a simple $2^{\Theta(n^{1-2\epsilon}\log(n))}$-time algorithm that, asymptotically, beats the straightforward $2^{\Theta(n^{1-\epsilon})}$ bound that follows from partitioning the graph into $O(n^\epsilon)$ many independent parts each of size $O(n^{1-\epsilon})$.


Multicasting in WDM core networks is an efficient way to economize network resources for several multimedia applications. Due to their complexity and cost, multicast capable switches are rare in the proposed architectures. The paper investigates the multicast routing without splitters in directed (asymmetric) graphs. The objective is to minimize the number of used wavelengths and if there are several solutions, choose the lowest cost one. We show that the optimal solution is a set of light-trails. An efficient heuristic is proposed to minimize conflicts between the light-trails, and so to minimize the number of used wavelengths. The performance is compared to existing light-trail based heuristics. Our algorithm provides a good solution with a few wavelengths required and a low cost.


Based on the principle of minimal energy and the coherent rotation model, two types of the jump phenomena, complete and incomplete jump phenomenon, are proved to exist in the angular dependence of the exchange bias with noncollinear unidirectional and uniaxial anisotropies. It is found that the transition between complete and incomplete jump phenomena occurs on condition that the exchange-coupling constant exceeds a critical value. Additionally, two different modes of the magnetization rotation, the whole-plane rotation, and the half-plane rotation are present in the magnetization reversal process, and they are dependent on the direction of the external field. Furthermore, the equations of the critical angle, at which orientation the exchange bias field reaches a maximum value and the coercivity disappears, are also derived in this paper. The numerical calculations in this paper are consistent with the relevant experimental observations, indicating that our method to study the angular dependence of the exchange bias as well as the magnetization reversal behaviors is valid. Our discussion about the jump phenomenon, the critical angle, and the modes of the magnetization reversal can explain the observed differences in results between different experiments.


Abstract Objectives The cephalosporin nitric oxide (NO)-donor prodrug DEA-C3D ('DiEthylAmin-Cephalosporin-3′-Diazeniumdiolate') has been shown to initiate the dispersal of biofilms formed by the Pseudomonas aeruginosa laboratory strain PAO1. In this study, we investigated whether DEA-C3D disperses biofilms formed by clinical cystic fibrosis (CF) isolates of P. aeruginosa and its effect in combination with two antipseudomonal antibiotics, tobramycin and colistin, in vitro. Methods β-Lactamase-triggered release of NO from DEA-C3D was confirmed using a gas-phase chemiluminescence detector. MICs for P. aeruginosa clinical isolates were determined using the broth microdilution method. A crystal violet staining technique and confocal laser scanning microscopy were used to evaluate the effects of DEA-C3D on P. aeruginosa biofilms alone and in combination with tobramycin and colistin. Results DEA-C3D was confirmed to selectively release NO in response to contact with bacterial β-lactamase. Despite lacking direct, cephalosporin/β-lactam-based antibacterial activity, DEA-C3D was able to disperse biofilms formed by three P. aeruginosa clinical isolates. Confocal microscopy revealed that DEA-C3D in combination with tobramycin produces similar reductions in biofilm to DEA-C3D alone, whereas the combination with colistin causes near complete eradication of P. aeruginosa biofilms in vitro. Conclusions DEA-C3D is effective in dispersing biofilms formed by multiple clinical isolates of P. aeruginosa and could hold promise as a new adjunctive therapy to patients with CF.


Abstract  Two methods of otolith increment analysis were used to describe spatial, temporal and gender variation in growth of sand whiting, Sillago ciliata (Cuvier), in four south-east Australian estuaries. Mean annual standardised otolith increment widths were used as indices of individual lifetime growth rates, while raw otolith increment widths were used to describe variation in growth throughout the life of S. ciliata. Temporal variation in growth was observed at an annual scale, while spatial variation in growth was observed between estuaries. Growth rates increased significantly with decreasing latitude and greater mean sea surface temperatures. A divergence in growth rates between sexes was detected, with females growing faster than males after sexual maturity. This study highlights how otolith increment analyses can: (1) be used to analyse temporal trends in growth from a single sample and (2) provide insight into juvenile growth when samples have an absence of undersized fish.


The COVID-19 pandemic is an eminent threat posed by nature to the survival of the whole community. The cost X it imposes upon the community can be mitigated by the community's pre-emptive public goods: an early warning system, capacity for monitoring, contact tracing and isolating infected persons, the strength of its public health system and the cultivated readiness to cooperate with anti-COVID protocols. The community provides these public goods in a nonstrategic game N (Nature) where the probability of a "bad outcome" (being symptomatically infected) falls with the total spending on pre-emptive public goods. Aside from N, members of the community play an Economic Dilemma Game (EDG), a symmetric Prisoner's Dilemma Game (PDG) with strategy set (C, D), where the community earns its economic income which in turn provides the financing of the pre-emptive public goods. Games EDG and N are fused into a composite game N+EDG by defining the probability of a good outcome as increasing with the level of public goods financing. N+EDG has the same strategy set (C, D) as EDG but the payoffs of players are composite: the payoff from EDG less the expected share of the pandemic cost to the members. We show that there is a threshold pandemic cost X0 (Ostrom threshold) so that if X ≥ X0, the N+EDG has dominant strategy in C. At the cooperative equilibrium, the community is at its peak strength: economic output from EDG is largest and the contribution to pre-emptive public good is highest. A severe-enough cost of the pandemic threat as perceived by the group (i) causes players to exhibit an altruistic phenotype (choosing C every time) and (ii) leads to the lowest probability of a bad outcome. We argue that previous experience with pandemics in the last two decades on top of a higher tendency to follow authority in East Asia supported both the provision of better pre-emptive public goods and the higher abidance with anti-COVID protocols. These explain better performance.


A Finite Element Analysis of a rigid sphere contact with a deformable elastic-plastic plat called indentation model is studied. The numerical results are applied on the rough surfaces contact of the GW model. A series of the relationships of the rough surfaces contact parameters are obtained. The contact parameters of the indentation model and the flattening model are compared in detail and the reasons for their differences are analyzed. In the case of single asperity contact, for ω/ωc > 1, the Indentation model reaches the initial plastic yield while the flattening model is ω/ωc = 1. In ω/ωc = 10, the plastic yield reaches the contact surface for the first time, and the corresponding point of ψ = 0.5 the flattening model is relatively earlier in . The contact parameters of rough surface in different plasticity indexes are compared again. On the point of ω/ωc = 6, the contact parameters of the flattening model and the indentation model coincide perfectly. For 0.5 < ψ < 4, the difference between the parameters curves become larger and larger. To the point of ψ = 4, when the distance difference reaches the maximum, it begins to decrease until the two curves are close to coincide again. The dimensionless elastic-plastic contact hardness is introduced. The relation between real contact area and the contact pressure of the indentation model can be acquired quickly. The results show that the geometric shape of deformable contact parts has an important effect on the contact parameters, especially for the extension of plastic deformation region within a specific range of plasticity index.


iportant item in the Declaration of Geneva is "My colleagues will be my brothers." It will be a gross violation of that ethical code if the B.M.A. or any other menber of the W.M.A. supports any move to expel, not the South African Government, but the M.A.S.A.-whose members are all our professional brethren who have not (as I trust this letter has shown) violated any part of the medical ethical code but, on the contrary, have maintained and are maintaining it under difficulties that have no parallel in any other country. They deserve fraternal commendation and support, not unbrotherly and unjustifiable condemnation.-I am, etc.,


Host range varies widely among species of parasitic plants. Parasitic plants realize host selection through induction by chemical molecular signals, including germination stimulants and haustoria-inducing factors (HIFs). Research on parasitic plant biology has provided information on germination, haustorium induction, invasion, and haustorial structures and functions. To date, some molecular mechanisms have been suggested to explain how germination stimulants work, involving a chemical change caused by addition of a nucleophilic protein receptor, and direct or indirect stimulation of ethylene generation. Haustorium initiation is induced by HIFs that are generated by HIF-releasing enzymes from the parasite or triggered by redox cycling between electrochemical states of the inducers. Haustorium attachment is non-specific, however, the attachment to a host is facilitated by mucilaginous substances produced by haustorial hairs. Following the attachment, the intrusive cells of parasites penetrate host cells or push their way through the host epidermis and cortex between host cells, and some types of cell wall-degrading enzymes may assist in the penetration process. After the establishment of host-parasite associations, parasitic plants develop special morphological structures (haustoria) and physiological characteristics, such as high transpiration rates, high leaf conductance, and low water potentials in hemiparasites, for nutrient transfer and resource acquisition from their hosts. Therefore, they negatively affect the growth and development and even cause death of their hosts.


The 1989 experiment by the Scripps Marine Physical Laboratory, studying sound propagation down the continental slope off Pt. Arguello and Pt. Conception, CA, has furnished evidence for the downslope conversion effect in which sound propagating down from a source over the continental shelf, by its interaction with the sloping ocean floor, gets trapped into the sound channel. As a consequence, the horizontal arrival structure observed at a distant receiver over deep water (the Scripps FLIP array, in this case) shows a flat ''pedestal'' shape centered at ±20° about the horizontal, while with a source also over deep water, a central minimum would be apparent due to Snell's law. Our calculations, using the CENTRO/ANTS normal mode code written by J. I. Arvelo and developed further at Catholic University, bears out the pedestal shape of the arrival structure. In these calculations, downslope propagation is treated adiabatically, and the bottom structure (sediment with underlying rock) is correctly taken into acc...


Reproductive males encounter potential mates under a range of circumstances that influence the costs, benefits or feasibility of alternative courtship tactics. Thus, males may be under strong selection to flexibly modify their behaviour. Red-sided garter snakes (Thamnophis sirtalis parietalis) in Manitoba overwinter in communal dens, and court and mate in large aggregations in early spring. The number of males within a courting group varies considerably, as do the body sizes of both males and females. We manipulated these factors to set up replicated courtship groups in outdoor arenas, and analysed videotapes of 82 courtship trials to quantify courting behaviours of male snakes. Larger and more heavy-bodied males courted more vigorously than did their smaller, thinner-bodied rivals, and large females attracted more intense courtship. The major effect, however, involved the number of rival males competing for copulation. Males in large groups not only reduced their overall vigour of courtship, but also modified their tactics in such a way as to benefit from the courtship activities of rival males. That is, they devoted less energy to inducing female receptivity (which requires energy-expensive caudocephalic waving) and more effort to behaviour (tail-searching) that enhanced their own probability of mating if the female gaped her cloaca. This social parasitism reveals an unsuspected plasticity and complexity in the behavioural tactics of reproducing male snakes.


In this study, radiation induced changes in a polymer gel dosimeter manufactured using 2-hydroxyethylacrylate (HEA) and N,N'-methylene-bisacrylamide (BIS) were investigated using magnetic resonance imaging (MRI) and FT-Raman spectroscopy. The variation in magnetic resonance relaxation time (T2) with absorbed dose was modelled assuming fast exchange of magnetization. Overall good agreement between the model and experimental data was obtained. However, comparison with FT-Raman data suggests that not all the protons attached to the polymer contribute to the relaxation process. Furthermore, for certain compositions improved agreement with experimental data was achieved when a lower fraction of polymer protons available for exchange with water was assumed in the low dose region. This indicates that the T2 value is influenced by the composition and topology of the formed polymer, which may vary with absorbed dose. The concept of percentage dose resolution (Dp delta, %) was introduced to enable optimization of gel compositions for use in relative dosimetry applications. This concept was applied to demonstrate the effects of varying the gelatine concentration, the total fraction of monomer/crosslinker (%T) and the relative fraction of crosslinker (%C) on gel performance in HEA gels as well as compare the performance of HEA and a standard polyacrylamide gel (PAG). The percentage dose resolution was improved for all HEA gels compared to the PAG dosimeter containing 3% acrylamide and 3% BIS. Increasing the total concentration of monomer was shown to have the largest single effect. In the range of doses of interest for clinical radiation therapy, Dp delta, % for the optimal HEA gel (4% HEA, 4% BIS) was lower than 2.3%, compared to 3.8% for the PAG dosimeter.


Placement Podcasts – Project Update Including the Employer's Perspective

The University of Huddersfield is one of the UK's top providers of sandwich education. Like other UK institutions, there is an awareness that as student expectations change the take up of placement opportunities needs to be more actively encouraged.

Often the best ambassadors for placements are the students who have already benefited from them. Therefore in 2007 an original project 'Placement Podcasts' was instigated which set out to document students talking about their placement experiences. This work was presented at WACE, 2007 in Singapore. Materials can now be viewed at: http://www.hud.ac.uk/tqef/placementvideo.html

Now, into its second phase, selected students are being 'followed' throughout their placement year, with the aim of recording their personal and professional development. To enable a broader perspective and cover the alternative dynamics of this partnership the views of both employers and placement tutors are also being sought. In particular, how the university sector is supporting the development of higher level skills.

The paper will focus on:
• The triangular partnership that exists between employer, student and the university.
• The views of the employers:
o The benefits they receive from the recruitment of work placement students.
o How employer insights may be used to inform course and curriculum development in a broad sense.
o How employers' views can influence our practice.
• Other topics to be covered include:
o Progress to date on the project
o Ongoing dissemination
o How technical issues have been addressed.
Video clips will additionally be used at the conference.


This paper provides an efficient way to design an automatic car braking system using Fuzzy Logic. The system could avoid accidents caused by the delays in driver reaction times at critical situations. The proposed Fuzzy Logic Controller is able to brake a car when the car approaches for an obstacle in the very near range. Collision avoidance is achieved by steering the car if the obstacle is in the tolerable range and hence there is no necessity to apply the brakes. Another FLC (which is cascaded with the first FLC for collision avoidance) implements the Anti-lock Braking capability during heavy braking condition. Thus the system is made intelligent since it could take decisions automatically depending upon the inputs from ultrasonic sensors. A simulative study is done using MATLAB and Lab view software. The results obtained by the simulation model are compared with the existing system and the proposed model conveys a satisfactory result which has high consumer acceptance.


The transition of homogeneous turbulence from an initially isotropic three-dimensional to a quasi-two-dimensional state is simulated numerically for a conducting, incompressible fluid under a uniform magnetic field B0. The magnetic Reynolds number is assumed to be small, so that the induced fluctuations of the magnetic field are small compared with the imposed magnetic field B0, and can be computed from a quasi-static approximation. If the imposed magnetic field is strong enough, all variations of the flow field in the direction of B0 are damped out. This effect is important e.g. in the design of liquid-metal cooling systems for fusion reactors, and the properties of the final state are relevant to atmospheric turbulence. An extended version of the code of Orszag & Patterson (1972) is used to integrate the Navier-Stokes equations for an incompressible fluid. The initial hydrodynamic Reynolds number is 60. The magnetic interaction number N is varied between zero and 50. Periodic boundary conditions are used. The resolution corresponds to 323 points in real space. The full nonlinear simulations are compared with otherwise identical linear simulations; the linear results agree with the nonlinear ones within 3% for about one-fifth of the large-scale turnover time. This departure is a consequence of the return-to-equilibrium tendencies caused mainly by energy transfer towards high wavenumbers. The angular energy transfer and the energy exchange between different components are smaller, and become virtually zero for large values of N. For N ≈ 50 we reach a quasi-two-dimensional state. Here, the energy transfer towards high wavenumbers is reduced for the velocity components perpendicular to B0 but relatively increased for the component parallel to B0. The overall behaviour is more similar to three-than to purely two-dimensional turbulence. This finding is of great importance for turbulence models of the atmosphere. The realization of a purely two-dimensional state does not seem to be possible for decaying turbulence. The magnetic field causes highly intensified pressure fluctuations, which contribute to the redistribution of the anisotropic Lorentz forcing.


Abstract Coagulation behaviour of polyaluminium chloride (PACl) was comparatively investigated in terms of the removal of turbidity and colour with surface water. The growth of flocs was also compared. The results show that the decrease in saturation and values of dissolved oxygen was ca. 20% for ALCAT and PAX 18 at both dosages and 15% for PAX XL 19H, respectively. The floc formation growth indicated that PACl coagulation occurred not only by charge neutralization but also by a form of sweep flocculation. Besides, flocs formed by ALCAT had better sizes than the flocs formed by PAX 18 and PAX XL19H. The rate of sedimentation was stable during coagulation with higher doses, and it was dependent on the substance used.


The payload oscillation inherent to all cranes makes it challenging for human operators to manipulate payloads quickly, accurately, and safely. Manipulation difficulty is also increased by nonintuitive crane-control interfaces. This paper describes a new interface that allows operators to drive a crane by moving a hand-held device (wand or glove) freely in space. A crane-mounted camera tracks the movement of the hand-held device, the position of which is used to drive the crane. Two control architectures were investigated. The first uses a simple feedback controller, and the second uses feedback and an input shaper. Two operator studies demonstrate that hand-motion crane control is faster and safer than using a standard push-button pendent control.


: Luteinizing hormone releasing hormone (LH-RH, luliberin) was revealed in the pineal organs of rats and cattle. The luliberin content per organ varied in rats from 5 to 66 ng, depending on sex and age. In some cases it could not be revealed by the direct radioimmunological method in the organ extracts, while neurohormone was detected by chromatography on carboxymethylcellulose or on Sephadex G-15. About 0.5 ng of LH-RH is contained in the bocine pineal organs, and the neurohormone competed with 125I-LH-RH for binding with a specific antiserum in the same way as synthetic luliberin. Mobility of LH-RH from the bovine and rat pineal organs during carboxymethylcellulose chromatography in the column coincided with such for synthetic LH-RH and the neurohormone from the rat hypothalamus. Besides, luliberin from the bovine pineal glands injected intraperitoneally to rats led to elevation of the LH blood level. No such effect occurred when luliberin from the epiphyses was preliminarily incubated with the LH-RH antiserum. A possible role played by luliberin in the pineal organ is discussed.


Purpose
The purpose of this study is to contribute to the debate in the literature about generalist CEOs by exploring the effect of board governance on CEO general managerial ability, focusing on one of the most crucial aspects of the board of directors, board size. Prior research shows that smaller boards constitute a more effective governance mechanism and therefore are expected to reduce agency costs.

Design/methodology/approach
The authors estimate the effect of board size on CEO general managerial ability, using a fixed-effects regression analysis, propensity score matching, as well as an instrumental-variable analysis. These techniques mitigate endogeneity greatly and make the results much more likely to show causality.

Findings
The results show that firms with smaller board size are more likely to hire generalist CEOs. Specifically, a decline in board size by one standard deviation raises CEO general managerial ability by 15.62%. A lack of diverse experiences in a small board with fewer directors makes it more necessary to hire a CEO with a broad range of professional experiences. Furthermore, the agency costs associated with generalist CEOs are greatly diminished in firms with a smaller board. Hence, firms with a smaller board are more inclined to hire generalist CEOs.

Originality/value
Although prior research has explored the effects of board size on various corporate outcomes, strategies and policies, this study is the first to investigate the effect of board size on CEO general managerial ability. This study contributes to the literature both in corporate governance and on CEO general managerial ability.


Malignant hyperthermia is a well-known rare life-threatening autosomal-dominant pharmacogenetic disease, The arti- cle deals with a halothane-caffeine contracture test. The test is a model of muscle reaction to triggers in-vitro and it is the "golden standard" for malignant hyperthermia susceptibility (MHS) diagnosis. Genetic analysis is less invasive, but its sensitivity is significantly lower. The review discusses both the methods which are essential to be completely reproduced in Russia, and their role in modern approach to MHS diagnosis.


: Closure of circular defects in the eyelids and canthal areas, as well as the face and neck regions, can present a challenging problem for the ophthalmic plastic surgeon. The O-to-Z plasty devised by Dr. Marvin Quickert is an excellent procedure for dealing with medium-sized circular defects in these regions. It is most commonly used after removal of benign or malignant tumors. In this procedure, skin is undermined from subcutaneous tissue and muscle around the entire circular defect. Two parallel incisions are made along normal lines of cleavage tangential to the circular defect. This allows the skin edges to be advanced and closed along a diagnol converting the defect to a Z closure. The advantage of this procedure is that it allows a smooth firm closure without a "dog-ear" defect. In addition, skin grafts can be avoided in closing many small- and moderate-sided circular defects.


The traditional regulatory approach to controlling pollution is inadequate in supporting sustainability, drawing attention to alternative strategies including self-regulation. However, such efforts rely on voluntary action on behalf of industry. Little research has been conducted to assess the effectiveness of these initiatives in the Canadian context.

Utilizing a combination of telephone and written questionnaires, Canadian manufacturing associations were surveyed to determine the extent to which voluntary environmental initiatives were promoted to their members.

The results indicate that only a small percentage of manufacturing associations promote formal voluntary environmental initiatives, suggesting that this form of self-regulation is not widely accepted by industry. These initiatives placed significant emphasis on legislative compliance and the goal and were deficient in key transparency and credibility indicators, suggesting that reliance on self-regulation alone is inadequate to address sustainable environmental management.


The objective of this study is to investigate under what circumstances Förster theory of electronic (resonance) energy transfer breaks down in molecular aggregates. This is achieved by simulating the dynamics of exciton diffusion, on the femtosecond timescale, in molecular aggregates using the Liouville–von Neumann equation of motion. Specifically the focus of this work is the investigation of both spatial and temporal deviations between exciton dynamics driven by electronic couplings calculated from Förster theory and those calculated from quantum electrodynamics. The quantum electrodynamics (QED) derived couplings contain medium- and far-zone terms that do not exist in Förster theory. The results of the simulations indicate that Förster coupling is valid when the dipole centres are within a few nanometres of one another. However, as the distance between the dipole centres increases from 2 nm to 10 nm, the intermediate- and far-zone coupling terms play non-negligible roles and Förster theory begins to break down. Interestingly, the simulations illustrate how contributions to the exciton dynamics from the intermediate- and far-zone coupling terms of QED are quickly washed-out by the near-zone mechanism of Förster theory for lattices comprising closely packed molecules. On the other hand, in the case of sparsely packed arrays, the exciton dynamics resulting from the different theories diverge within the 100 fs lifetime of the trajectories. These results could have implications for the application of spectroscopic ruler techniques as well as design principles relating to energy harvesting materials.


To accurately predict how ecosystems will respond to climate change – and how management actions can influence such responses – scientists and managers need a better understanding of how and when biotic interactions modify climate–growth relationships. However, current research has largely ignored the role of competition in modulating climate–growth relationships of mature trees. In this study, we assessed the effect of competition on tree responses to drought and interannual climate variability as well as linkages between climate sensitivity and morphological characteristics of the stem wood. We sampled 10 sites in north‐eastern Washington, USA, and used dendroecology to quantify responses of Douglas‐fir (Pseudotsuga menziesii) to drought and climate variability. Tree‐ring series were converted to basal area increment series, and the effects of competition on climate–growth relationships were assessed at the tree and site levels using a combination of correlation analyses and linear mixed‐effects models. Competition did not affect tree responses to extreme drought. When soil moisture was below average, tree growth was tightly coupled to climate variability for all trees, regardless of their competitive status. However, in wet years, competition had a pronounced, positive effect on climate sensitivity of growth. Trees with more competition from neighbours exhibited a significantly higher proportion of sapwood area in latewood (a morphological trait associated with greater drought resistance). Synthesis. Our results suggest that a tree's ability to cope with environmental variability is driven not just by the proximate effects of neighbours on resource availability, but also by phenotypic plasticity and long‐term adaptations to competitive stress (such as changes in carbon allocation). Findings have important implications for individual‐tree and stand‐level growth models and may help managers better understand how their activities will modify tree responses to climate change.


Opportunistic scheduling exploits the multiuser diversity to improve the performance of wireless communications. The scheduling gain is enabled by the channel feedback sent from the receiver to the transmitter. In this paper, we consider the so-called opportunistic cumulative distribution function (CDF) scheduling with threshold-based selective feedback in the orthogonal frequency division multiple access downlink system. Among opportunistic scheduling techniques, the CDF scheduling is known to provide multiuser diversity gain while maintaining fair radio resource sharing among users. We first derive the exact and asymptotic average sum rates assuming antenna selection at transmitters. The expressions are valid for arbitrary number of inter-cell interference and number of transmit antennas. Moreover, a closed-form approximation for the user rate distribution is calculated using the exact moments of the user sum rate. The approximation is shown to provide an accurate estimate for the rate distribution, and the results can be utilized in rate adaptation at the transmitter.


Vehicle registration system is an essential process for recording the transfer of vehicles' ownership. Most of existing systems are administratively centralized, semi‐automated, and rely on a formal proof provision. While these systems were initially proposed to preserve the owner's rights, prove their ownerships and legally record used motor‐land transportation means. Unfortunately, these systems also allow the registration of illegally smuggled and stolen vehicles. This is mainly due to inefficient verification methods, long heterogeneous administrative procedures or to corrupt individuals at the motor registration departments. Regardless of the reasons, the fact that the system allows such cases hints on a faulty design. Current systems are centralized and do not perform a double checking until a report is made, which means that this occurs after the fact of registering the forged vehicle. Noting that these reports are not always fruitful, if the vehicle's proofs were properly injected in the system. This paper proposes a system that is transparent where every vehicle registration is done under everyone's watchful eyes. No denying, no alteration, and no unauthorized injection may occur. The proposed system saves the owner's information and the vehicle's descriptions in transactions saved in a public blockchain where all the history of purchases regarding the subject vehicle may be tracked. The use of blockchain technology is motivated by its security, transparency, and traceability as well as its immutability and scalability in terms of users. We have evaluated our proposed solution in terms of its security and resiliency to the injection of forged transactions by the elaboration of the attack tree. The results show our solution's superiority when compared against current registration system.


Generative Adversarial Networks (GANs) is a powerful family of models that learn an underlying distribution to generate synthetic data. Many existing studies of GANs focus on improving the realness of the generated image data for visual applications, and few of them concern about improving the quality of the generated data for training other classifiers -- a task known as the model compatibility problem. As a consequence, existing GANs often prefer generating `easier' synthetic data that are far from the boundaries of the classifiers, and refrain from generating near-boundary data, which are known to play an important roles in training the classifiers. To improve GAN in terms of model compatibility, we propose Boundary-Calibration GANs (BCGANs), which leverage the boundary information from a set of pre-trained classifiers using the original data. In particular, we introduce an auxiliary Boundary-Calibration loss (BC-loss) into the generator of GAN to match the statistics between the posterior distributions of original data and generated data with respect to the boundaries of the pre-trained classifiers. The BC-loss is provably unbiased and can be easily coupled with different GAN variants to improve their model compatibility. Experimental results demonstrate that BCGANs not only generate realistic images like original GANs but also achieves superior model compatibility than the original GANs.


The present study was designed to compare the life history traits of two Podarcis muralis populations located at sites of different elevation. The age at maturity was similar in both populations, whereas longevity was found to be lower in the lowland one (Derekoy). The males and females of both populations had a similar snout-vent length (SVL) and mean age. Sexual size dimorphism (SSD) was weak in the highland population, males being slightly larger than females, whereas a strong male-biased SSD was observed in the lowland one. The growth coefficient ( k ) and growth rates were similar in both populations. This study indicates that the age at maturation (2-3 years) and growth rates (2.37 mm/year) are similar in two populations of P. muralis exposed to different climatic and environmental conditions. Longevity was slightly higher in the highland population (16 years) compared to the lowland one (14 years).


This paper reports an analysis of the websites of UK departments of library and information science. Inlink counts of these websites revealed no statistically significant correlation with the quality of the research carried out by these departments, as quantified using departmental grades in the 2001 Research Assessment Exercise and citations in Google Scholar to publications submitted for that exercise. Reasons for this lack of correlation include: difficulties in disambiguating departmental websites from larger institutional structures; the relatively small amount of research-related material in departmental websites; and limitations in the ways that current web search engines process linkages to URLs. It is concluded that departmental-level webometric analyses do not at present provide an appropriate technique for evaluating academic research quality, and, more generally, that standards are needed for the formatting of URLs if inlinks are to become firmly established as a tool for website analysis.


Background: Drug-environment associative memory mechanisms and the resulting conditioned behaviors are key contributors in relapse to cocaine dependence. Recently, we reported rat amygdala phospholipase D as a key convergent downstream signaling partner in the expression of cocaine-conditioned behaviors mediated by glutamatergic and dopaminergic pathways. In the present study, 1 of the 2 known upstream serotonergic targets of phospholipase D, the serotonin (5-hydroxytryptamine) 2C receptor, was investigated for its role in recruiting phospholipase D signaling in cocaine-conditioned behaviors altered in the rat amygdala and dorsal hippocampus. Methods: Using Western-blot analysis, amygdala phospholipase D phosphorylation and total expression of phospholipase D/5-hydroxytryptamine 2C receptor were observed in early (Day-1) and late (Day-14) withdrawal (cocaine-free) states among male Sprague-Dawley rats subjected to 7-day cocaine-conditioned hyperactivity training. Functional studies were conducted using Chinese Hamster Ovary cells with stably transfected human unedited isoform of 5-hydroxytryptamine 2C receptor. Results: Phosphorylation of phospholipase D isoforms was altered in the Day-1 group of cocaine-conditioned animals, while increased amygdala and decreased dorsal hippocampus phospholipase D/5-hydroxytryptamine 2C receptor protein expression were observed in the Day-14 cocaine-conditioned rats. Functional cellular studies established that increased p phospholipase D is a mechanistic response to 5-HT2CR activation and provided the first evidence of a biased agonism by specific 5-hydroxytryptamine 2C receptor agonist, WAY163909 in phospholipase D phosphorylation 2, but not phospholipase D phosphorylation 1 activation. Conclusions: Phospholipase D signaling, activated by dopaminergic, glutamatergic, and serotonergic signaling, can be a common downstream element recruited in associative memory mechanisms altered by cocaine, where increased expression in amygdala and decreased expression in dorsal hippocampus may result in altered anxiety states and increased locomotor responses, respectively.


The cyst nematode, Globodera tabacum tabacum Behrens, and the parasitic angiosperm, Egyptian broomrape, Orobanche aegyptiaca Pers., are obligate root parasites that cause severe yield and quality loss of many important crop hosts. Although these represent two diverse classes of parasites, they have significant similarities in the modes of parasitism and complex interactions with their hosts. Conventional control methods have had limited success in controlling these parasites. The overall objective of this research was to engineer resistance to the cyst nematode and Egyptian broomrape by expressing genes encoding parasite specific toxins under the control of parasiteresponsive promoters using tobacco (Nicotiana tabacum L. cv. Xanthi). For nematode resistance, an anti-feeding strategy was employed utilizing the tomato proteinase inhibitor I (PI-I) gene as a nematode specific toxin. Transgenic tobacco plants were generated that expressed genes encoding an intracellarly retained or secreted form of tomato PI-I under the control of the nematode-inducible promoter, derived from tomato (Lycopersicon esculentum L.) Hmg2 gene. Our goals were to determine the effectiveness of local PI-I expression on nematode resistance and to determine if intracellular or extracellular PI-I deposition enhances resistance. Two constructs were generated that contained either the coding region of the tomato PI-I gene, lacking the signal sequence (EM1), or the coding region of PI-I including the signal sequence (EM2), fused to the nematode-responsive Hmg2 promoter. Transgenic PI-I plants were inoculated with G. t. tabacum cysts and evaluated for nematode interactions. Our results suggest that local expression of intercellular of PI-I significantly reduced cyst production when compared to the nontransformed controls. For broomrape resistance, a well characterized R/avr gene pair, the tobacco N resistance gene and the tobacco mosaic virus replicase (TMV) gene, was utilized to create novel gene-for-gene resistance via a N gene-mediated hypersensitive response (HR) to limit broomrape parasitism. The bean (Phaselous vulgaris L.) chalcone synthase 8 (CHS8) promoter has been characterized as a broomrape–responsive promoter. We introduced the CHS8:TMV replicase gene construct into tobacco plants that contains an endogenous N gene. Transgenic tobacco plants were inoculated with O. aegyptiaca seeds and monitored for parasite attachment and development. The expression of the TMV replicase leads to a significant reduction in broomrape parasitism. These genetic engineering strategies show promise in enhancing resistance to these destructive parasites.


This study aims to investigate Indonesian government policy on the environmental law in the era of regional autonomy by analyzing the by the conception of Indonesian government policy towards regional autonomy or decentralization, the relation between regional autonomy policy and law enforcement and violation to the environment and the Indonesian government's strategic policy towards environmental law in the era of regional autonomy. The methodology in this research uses a qualitative method with a descriptive research design. The results showed that the laws and regulations relating to environmental management are sufficient, but in their implementation, including in the supervision of their implementation, they need to receive serious attention. This is closely related to the good intentions of the government including the regional government, the community and the parties concerned to manage the environment as well as possible.


Delivering large media files over the Internet is a challenging task because it has some unique features that are different from delivering conventional Web documents. In this paper, we propose a fine-grained peer sharing technique for dealing with the problem in the context of content distribution networks. The key difference of the technique from conventional peer-to-peer systems is that the unit of peer sharing is not a complete media file, but at a finer granularity. By doing so, we improve the flexibility of replica servers for handling client requests. We analyze the storage requirement at replica servers and design a scheduling algorithm to coordinate the delivery process from multiple replica servers to a client. Our simulations show that the fine-grained peer sharing approach can reduce the initial latency of clients and the rejection rate of the system significantly over a simple peer sharing method


Multiple sclerosis (MS) is a chronic inflammatory disease that results in autoimmune demyelination of the human central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) is a widely-studied animal model of multiple sclerosis which reflects many of the histopathological and immunological features of MS. Because currently used therapies for multiple sclerosis result in broad-spectrum immunosuppression antigen specific vaccines may be an important alternative. Whereas the concept of traditional anti-microbial vaccination is to introduce the immune system with the foreign microbes to develop memory T and B cells self-reactive T cell suppression is the fundamental principle of tolerogenic vaccines. For EAE contemporary research is focused on the development of potent tolerogens. Fusion proteins of cytokine and neuroantigen (NAg) are assumed to be such potent tolerogens. Antigen presenting cells (APC) are targeted by the fusion proteins in a cytokine dependent manner. These APC have been shown to play a fundamental role in inducing sustainable self-tolerance. That is autoimmune effector T cells are eliminated by regulatory T (Treg) cells that are stimulated and expanded in a negative thymic selection process where dendritic cells (DC) play an inevitable role. The principle is that the cytokine domain of the fusion protein will interact with cytokine receptors on the APC and facilitate the presentation of covalently linked NAg to self reactive T cells and thereby induce a co-inhibitory signal leading to cytotoxicity and killing of NAg-specific autoreactive T cells. In an approach to induce tolerogenic response in EAE I have studied two fusion proteins consisting of interferon-beta (IFN-[beta]) fused to myelin oligodendrocyte glycoprotein (MOG) and IFN-[beta] fused to proteolipid peptide (PLP). Both fusion proteins were potent tolerogens. The fusion genes were cloned in pIRES2 expression plasmids and then expressed stably in human embryonic kidney cells and the fusion proteins were purified by affinity chromatography. Functional integrity of the IFN-[beta] domain within the fusion protein was confirmed by a T cell anti-proliferative assay and a class-I MHC induction assay. Biological activity of NAg domains were tested by NAg specific T cell proliferative assays. The tolerogenic effect of the fusion protein was assessed in two ways. First the preventive role of IFN-[beta]-PLP was examined by administering the protein before EAE induction which inhibited the subsequent incidence of EAE. Second IFN-[beta]-MOG was administered after disease onset which halted disease progression. In both cases covalent linkage between the IFN-[beta] and NAg domain was required to restore the tolerance.