Metronidazole (MTZ) is a widely used drug, but due to its many side effects, there is a growing trend today to use a minimum dose while maintaining high efficacy. One way to meet this demand is to reduce the size of the drug particles. A relatively new method of size reduction is attaching the drug molecules to a mesoporous carrier. In this paper, we studied the fixation of MTZ molecules on mesoporous silica carriers. The drug was immobilized on two mesoporous silica materials (Syloid, SBA-15) with the use of a variety of immersion techniques and solvents. The immobilized drug was subjected to physicochemical examinations (e.g., SEM, XPS, XRD, nitrogen uptake, DSC) and dissolution studies. A significantly higher immobilization was attained on SBA-15 than on a Syloid carrier. Among the processing parameters, the type of MTZ solvent had the highest influence on immobilization. Ultrasonic agitation had a lower but still significant impact, while the concentration of MTZ in the solution made no difference. Under optimal conditions, with the application of an ethyl acetate solution, the surface coverage on SBA-15 reached as much as 91%. The immobilized MTZ exhibited a ca. 10% faster dissolution rate as compared to the pure micron-sized drug particles.


The space of higher education has been receiving enough disruptions lately from the vast amount of advancements in technology. They are forced to adapt to the dynamic demands, tools, and other technological changes that can be overwhelming. This adaptation to technological changes is often referred as digital transformation, which is unavoidable, unless if the institution is ready to be deemed irrelevant. This paper will start the discussion on the topic of this transformation; the role of university, why the transformation is needed, and what are the challenges that come with such transformation.


The objective of this article is to assess whether the recent economic evolution of EU accession countries and their expected developments for the coming years put them in a better or a worse position to join the euro. Using structural vector autoregression models, the results show that shocks are more asymmetric in candidate countries than in current euro-zone members and that the situation has worsened in the most recent years. However, it seems that monetary policies in accession countries are closely influenced by monetary conditions in the euro zone. If this is the case, then the costs of losing monetary independence when joining the euro would be reduced. In any case, and considering that, on average, correlations are still far from the values of the euro-zone countries, the flexibility of real sector and labor markets will be essential for the sustainability of joining the euro.


Production grids have a potential for parallel execution of a very large number of tasks but also introduce a high overhead that significantly impacts the execution of short tasks. In this work, we present a strategy to optimize the partitioning of jobs on a grid infrastructure. This method takes into account the variability and the difficulty to model a multi-user large-scale environment used for production. It is based on probabilistic estimations of the grid overhead. We first study analytically modeled environments and then we show results on a real grid infrastructure. We demonstrate that this method leads to a significant time speed-up and to a substantial saving of the number of submitted tasks with respect to a blind maximal partitioning strategy.


Objective. To assess the evolution of preexisting extraarticular manifestations of rheumatoid arthritis (EA-RA) in patients treated with anti-tumor necrosis factor-α (TNF-α), as well as the development of new EA-RA. Methods. We assessed EA-RA in 152 patients receiving anti-TNF-α treatment. Results. In 22 cases, a new EA-RA developed. In 5 cases, there was evidence of progression of preexisting EA-RA. Regression was found in 4 cases. Some patients were in disease remission when they developed EA-RA, whereas some patients had moderate/high disease activity. Conclusion. EA-RA are still present in patients treated with anti-TNF-α. Development of new severe EA-RA is rare in patients receiving anti-TNF therapy.


Tidally-generated, trapped motions can signie cantly enhance and modify sea level and currents in the island proximity. The analytical solution for incident waves interacting with a cylindrical island with a circular sill has been constructed to investigate this phenomenon. To derive solutions for the scattering problems simple Sverdrup and Kelvin waves are used as incident waves. The amplie cation of the signal along the island perimeter has shown to be a function of frequency, relative dimensions of the island and the circular sill surrounding the island, relative sill depth, and the bottom friction. Although the incident diurnal tide may be amplie ed through the resonant response, this resonance occurs in the shallow water where the bottom friction damps the effect. The dispersion equation shows that the geometry of the problem favors amplie cation of semidiurnal tides. Analytical solutions obtained by superposition of the incident and scattered waves around an island are used to explain the observed peculiarities of tides in the vicinity of the Pribilof Islands, Bering Sea.


This research focuses a new method of using data obtained from CT images combined with digital CAD and rapid prototyping model for the surgical planning of difficult corrective and this new application enables the surgeon to choose the proper configuration and location of internal fixation of plate on humerus bone in the field of orthopaedics. This paper presents the procedure for making model of humerus bone using rapid prototyping technologies [RPT]. Production of prototypes for medical modeling (orthopaedics) in general can be classified into two broad categories based on manufacturing process route and type of data available, i.e. designed data and scanned/digitized data. Designed data is data that is created according to a person's idea on computer aided design (CAD) system. For this type of data, the designer has total control to modify, adjust and manipulate his design ideas to serve the functional purpose of his design. Producing models with this type of data is very straightforward and no further data treatment is required. CAD solid model can be directly converted to STL format for use in subsequent rapid prototyping process. For this type of data, the user has limited capability to modify and manipulate the geometry and further processing is required before they can be readily used by rapid prototyping system. For example, further data treatment is needed for Scanned data from computed tomography (CT) and agnatic resonance imaging (MRI) scanners which capture soft and hard tissue information based on density threshold value. The undesired soft tissue data is removed before it is sent to rapid prototyping machine for fabrication.


Epstein Barr virus (EBV) has been implicated in the pathogenesis of oral hairy leukoplakia (OHL). EBV is normally detected by lesional biopsy. The objectives of this study were to examine oral scrapes containing squamous epithelial cells (squames) from HIV-infected people with and without clinical lesions of OHL, and from healthy non-HIV-infected controls, for EBV-DNA by the polymerase chain reaction (PCR). EBV-DNA was detected in 65% of HIV-infected people and 20% of healthy HIV-negative controls but in HIV-infected individuals it was found as frequently in those without OHL as in those with. Moreover, EBV-DNA was not detected in all HIV-infected individuals, nor in all OHL. The results suggest that the presence or absence of detectable EBV-DNA in oral scrapes, though a guide, cannot be regarded as absolutely reliable in the diagnosis or exclusion of OHL.


Using positron emission tomography (PET) and intravenously injected (13)N(2), we assessed the topographical distribution of pulmonary perfusion (Q) and ventilation (V) in six healthy, spontaneously breathing subjects in the supine and prone position. In this technique, the intrapulmonary distribution of (13)N(2), measured during a short apnea, is proportional to regional Q. After resumption of breathing, regional specific alveolar V (sVA, ventilation per unit of alveolar gas volume) can be calculated from the tracer washout rate. The PET scanner imaged 15 contiguous, 6-mm-thick, slices of lung. Vertical gradients of Q and sVA were computed by linear regression, and spatial heterogeneity was assessed from the squared coefficient of variation (CV(2)). Both CV and CV were corrected for the estimated contribution of random imaging noise. We found that 1) both Q and V had vertical gradients favoring dependent lung regions, 2) vertical gradients were similar in the supine and prone position and explained, on average, 24% of Q heterogeneity and 8% of V heterogeneity, 3) CV was similar in the supine and prone position, and 4) CV was lower in the prone position. We conclude that, in recumbent, spontaneously breathing humans, 1) vertical gradients favoring dependent lung regions explain a significant fraction of heterogeneity, especially of Q, and 2) although Q does not seem to be systematically more homogeneous in the prone position, differences in individual behaviors may make the prone position advantageous, in terms of V-to-Q matching, in selected subjects.


Abstract Purpose This article evaluates the effect of antiepileptic drugs (AEDs) on thyroid function tests in children with epilepsy. Methodology One hundred twenty children were studied, with 40 patients taking older generation AEDs Na valproate (N = 20) and carbamazepine (N = 20), 40 patients taking newer generation AEDs levetiracetam (N = 20) and oxcarbazepine (N = 20), and 40 healthy children as controls. Serum T3, T4, FT4, and thyroid-stimulating hormone (TSH) were measured. Results Patients taking Na valproate had lower T3, T4, and a higher TSH level than controls. Patients taking carbamazepine had the lowest T3, T4, and FT4 serum levels among patients receiving AEDs. Conclusion The thyroid function tests were affected by the use of Na valproate and carbamazepine compared to both the control group and the group taking newer AEDs oxcarbazepine and levetiracetam. In addition, there was no effect of levetiracetam on thyroid function test results.


Abstract. Analyzing optical remote sensing imagery depends heavily on their spatial resolution. At the same time, this data is adversely affected by fixed sensor parameters and environmental influences. Methods for increasing the quality of such data and concomitantly optimizing its information content are, thus, in high demand. In particular, single-image super-resolution (SISR) approaches aim to achieve this goal solely by observing the individual images.We propose to adapt a generic deep residual neural network architecture for SISR to deal with the special properties of remote sensing satellite imagery, especially taking into account the different spatial resolutions of individual Sentinel-2 bands, i.e., ground sampling distances of 20 m and 10 m. As a result, this method is able to increase the perceived resolution of the 20 m channels and mesh all spectral bands. Experimental evaluation and ablation studies on large datasets have shown superior performance compared to the state-of-the-art and that the model is not bound by its capacity.


As embedded systems grow increasingly complex, there is a pressing need for diagnosing and monitoring capabilities that estimate the system state robustly. This paper is based on approaches that address the problem of robustness by reasoning over declarative models of the physical plant, represented as a variant of factored Hidden Markov Models, called Probabilistic Concurrent Constraint Automata. Prior work on Mode Estimation of PCCAs is based on a Best-First Trajectory Enumeration (BFTE) algorithm. Two algorithms have since made improvements to the BFTE algorithm: 1) the Best-First Belief State Update (BFBSU) algorithm has improved the accuracy of BFTE and 2) the MEXEC algorithm has introduced a polynomial-time bounded algorithm using a smooth deterministic decomposable negation normal form (sd-DNNF) representation.

This paper introduces a new DNNF-based Belief State Estimation (DBSE) algorithm that merges the polynomial time bound of the MEXEC algorithm with the accuracy of the BFBSU algorithm. This paper also presents an encoding of a PCCA as a CNF with probabilistic data, suitable for compilation into an sd-DNNF-based representation. The sd-DNNF representation supports computing k belief states from k previous belief states in the DBSE algorithm.


Cuttings reinjection is an effective way to treat oilfield waste. There is still a risk of slurry leakage during the field operations although cuttings re-injection technology has been widely used. The study of fracture initiation and propagation during cuttings re-injection is important for operational design. Fracturing is a complex physical process that combines fluid seepage, temperature diffusion, stress change, and rock damage. In offshore cuttings re-injection projects, the temperature difference between the injection slurry and the formation has a significant impact on the fracture behaviors, especially in high-temperature-high-pressure (HTHP) formations. In this paper, a fully coupled thermal-hydraulic-mechanical (THM) model was developed by the cohesive element method for modeling cuttings re-injection. The multi-physical field evolution in cuttings re-injection process in HTHP offshore formation was studied. The simulation results show that the cooling effect of the injection fluid causes the contraction of the formation which leads to an increase in the tensile stress of the rock and a decrease in the formation fracture pressure. The cooling effect results in a wider and shorter fracture than the case without the consideration of the cooling effect. Therefore, it allows more slurry to be injected in a limited near-wellbore zone, reducing the risk of slurry leakage during the injection process. The cooling effect is positively correlated with the temperature difference between the injection slurry and the formation.


Reviewed by Lucia Belles-CalveraIULMA / Universitat Jaume I, Spain

Multimodality in Higher Education, by Archer and Breuer (2016) deals with multimodal writing practices and pedagogies in tertiary education. With the boost of new technologies in the field of education, studies on modes of communication (e.g. writing) have focused on their evolution throughout the years, particularly in the learning process.
This book is aimed at educators and researchers who are interested in the writing communication practices required in a variety of domains, namely architecture, engineering or cultural studies among others. It is true that Multimodality has become quite complex in the past few years given that writing is regarded as a means of knowledge even in practical fields, such as science and media production. In this sense, this volume could be used as a resource book for those educators who want to reflect on the relevance of multimodal competencies when conveying a message, especially when they want to suit students' needs in the near future. At the same time, the content of the book is precise and easy to follow as it includes interviews and pictures that can help readers understand the changes that have taken place in the communication landscape.


The general characteristics of the main salmon (Salmo salar L.) stocks in the Massif armoricain (Brittany and Lower Normandy), in the Loire-Allier and in the Adour-Gaves-Nive have been summarized. Due to the poor quality of the previous fishing statistics, there is no clear picture of the historical evolution of the salmon stock. However, a dramatic decrease in the endemic range of Atlantic salmon in France can be shown since the mid-18th century and more particularly during the last 50 years. The lack of precise informations describing the size of the catches and the levels of exploitation at sea and in the estuaries make it impossible to estimate the impact that exploitation has led on the evolution of salmon stocks. The mean age of salmon in freshwater ranges from 1 to 1.5 years. The Loire-Allier basin is characterized by a relatively high proportion of large salmon (3 fish) in the rod catches. Fish native to Brittany and Lower-Normandy (Massif armoricain) have lower growth rates than those from the Loire-Allier and Adour-Gaves-Nive Basins. A greater proportion of the early grilse stocks (migration May-July) are males than compared with fish running later. The sex ratio of the multi-sea-winter salmon is biased towards females.


This paper presents an efficient mechanism to achieve significant energy savings in heterogeneous wireless sensor networks such as HPWREN. Environmental sensors are typically located in remote and hard-to-reach locations far from the main high-bandwidth data links. Therefore the sensed data needs to be routed through multiple hops before reaching the backbone. The routing is done by battery-powered nodes using license free radios such as 802.11. In this context, minimizing energy consumption is critical to maintaining operational data links. We propose a distributed low-power scheduling algorithm that limits the number of active nodes and allows a large portion of nodes to sleep. The algorithm works in a completely distributed manner, requiring handshaking only when a node enters and exits the network. Routing of packets relies on a dynamically changing backbone of nodes. The nodes of the backbone provide connectivity and are responsible for delivering the packets to the proper destinations. The proposed solution sits on top of the unmodified MAC layer so that legacy network devices can be used, and expensive hardware/software modifications are avoided. Thus our solution is cheap yet easily deployable. Our results show up to 60% energy savings per battery operated node while maintaining efficient data delivery.


We investigate the formation and properties of low surface brightness galaxies (LSBGs) with M* > 109.5 M⊙ in the eagle hydrodynamical cosmological simulation. Galaxy surface brightness depends on a combination of stellar mass surface density and mass-to-light ratio (M/L), such that low surface brightness is strongly correlated with both galaxy angular momentum (low surface density) and low specific star formation rate (high M/L). This drives most of the other observed correlations between surface brightness and galaxy properties, such as the fact that most LSBGs have low metallicity. We find that LSBGs are more isolated than high-surface-brightness galaxies (HSBGs), in agreement with observations, but that this trend is driven entirely by the fact that LSBGs are unlikely to be close-in satellites. The majority of LSBGs are consistent with a formation scenario in which the galaxies with the highest angular momentum are those that formed most of their stars recently from a gas reservoir co-rotating with a high-spin dark matter halo. However, the most extended LSBG discs in EAGLE, which are comparable in size to observed giant LSBGs, are built up via mergers. These galaxies are found to inhabit dark matter haloes with a higher spin in their inner regions (<0.1r200c), even when excluding the effects of baryonic physics by considering matching haloes from a dark-matter-only simulation with identical initial conditions.


Albendazole (ABZ) presystemic clearance was studied in rat by perfusion of a 25 microM ABZ solution in isolated intestinal loops. Significant secretion of the active metabolite, ABZSO, into the lumen was observed. The metabolite was also present in mesenteric blood. After 30 min of intestinal perfusion, 64% of the ABZ dose had disappeared from lumen. The total amount of ABZSO measured was 0.341 +/- 0.04 nmol/cm with 0.176 +/- 0.03 nmol/cm in mesenteric blood. The metabolite secretion to intestinal lumen was 0.165 +/- 0.05 nmol/cm. Intestinal sulfoxidation was induced by repeated administration of ABZ and ABZ coadministered with surfactants, especially polysorbate 80. The enantioselectivity of the in vitro intestinal sulfoxidation of ABZ showed that the relative contribution of P-450 and flavin-containing monooxygenase was quite similar, but after the induction by ABZ coadministered with polysorbate 80, the cytochrome P-450 system contribution was significantly increased. The appearance of ABZSO in mesenteric blood clearance was also increased under these conditions.


Eight 1-[(2-chlorophenyl)carbamoyl]naphthalen-2-yl alkylcarbamates and eight 1-[(2-nitrophenyl)carbamoyl]naphthalen-2-yl alkylcarbamates were tested for their activity related to the inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. The PET-inhibiting activity of the compounds was relatively low; the corresponding IC50 values ranged from 0.05 to 0.664 mmol/L; and the highest activity within the series of compounds was observed for 1-[(2-chlorophenyl)-carbamoyl]naphthalen-2-yl propylcarbamate. It has been proven that the compounds are PET-inhibitors in photosystem II. Despite rather low PET-inhibiting activities, primary structure-activity trends can be discussed.


This paper presents a strategy for seeding streamlines in 3D flow fields. Its main goal is to capture the essential flow patterns and to provide sufficient coverage in the field while reducing clutter. First, critical points of the flow field are extracted to identify regions with important flow patterns that need to be presented. Different seeding templates are then used around the vicinity of the different critical points. Because there is significant variability in the flow pattern even for the same type of critical point, our template can change shape depending on how far the critical point is from transitioning into another type of critical point. To accomplish this, we introduce the /spl alpha/-/spl beta/ map of 3D critical points. Next, we use Poisson seeding to populate the empty regions. Finally, we filter the streamlines based on their geometric and spatial properties. Altogether, this multi-step strategy reduces clutter and yet captures the important 3D flow features.


In the identification, evaluation and acquisition of suitable computer related software products and skills, as well as Internet products and skills, organisations have continuously sought to streamline their business processes. Historically the route taken has been dictated by the outcome of previous decisions — organisations have been governed by their chosen hardware and software environments or had to justify significant re-investment in a change of direction. This could, however, all be about to change radically in the immediate future.


{[Fe(I)Pc(-2)(-)]·(TMP(+))}·0.5C6H14 (1) and {Co(i)Pc(-2)(-)}·(TMP(+)) (2) salts containing iron(I) and cobalt(I) phthalocyanine anions and N,N,N'-trimethylpiperazinium cations (TMP(+)) have been obtained as single crystals. The TMP(+) cations coordinate to the iron(I) centers in 1 by free nitrogen atoms to form a weak N(TMP(+))-Fe bond of 2.568(3) and 2.553(3) Å length at 150 and 105 K, respectively. This is the first zwitterionic assembly containing anions and cations in one neutral coordination {[Fe(I)Pc(-2)(-)]·(TMP(+))} unit. The Fe(I)Pc(-2)(-) anions manifest strongly asymmetric EPR signals in the spectrum of 1 which can be fitted well by four components at 298 K with g1 = 2.1770, g2 = 2.1681, g3 = 2.1425 and g4 = 2.0708. The signal is attributed to the low-spin (S = 1/2) Fe(I) with the d(7) configuration. The EPR spectrum of 1 does not change qualitatively upon slow cooling from 298 down to 4 K. Quenching of the sample for seconds produces a different EPR spectrum at 4 K. This spectrum can be attributed to the frozen metastable state of Fe(I)Pc(-2)(-) which exists only at low temperatures and transfers to the spectrum observed for the slowly cooled sample above 70 K. Salt 2 contains EPR silent cobalt(I) with the d(8) configuration and in this case the TMP(+) cations do not coordinate to the cobalt(I) atoms.


Current challenges in microRNA (miRNA) research are to improve the identification of in vivo mRNA targets and clarify the complex interplay existing between a specific miRNA and multiple biological networks. MiRonTop is an online java web tool that integrates DNA microarrays or high-throughput sequencing data to identify the potential implication of miRNAs on a specific biological system. It allows a rapid characterization of the most pertinent mRNA targets according to several existing miRNA target prediction approaches. It also provides useful representations of the enrichment scores according to the position of the target site along the 3-UTR, where the contribution of the sites located in the vicinity of the stop codon and of the polyA tail can be clearly highlighted. It provides different graphs of miRNA enrichment associated with up-or down-regulated transcripts and different summary tables about selections of mRNA targets and their functional annotations by Gene Ontology.


We revisit the evaluation of the pionic mechanism of the $\bar{u}-\bar{d}$-asymmetry in the proton structure function. Our analysis is based on the unitarity relation between contributions of different mechanisms to the inclusive particle production and the total photoabsorption cross-section (i.e. the proton structure function). We reanalyze the role of isovector reggeons in inclusive production of nucleons and Delta isobars in hadronic reactions. A rather large contribution of reggeon-exchange induced production of Delta isobars is found. This leaves much less room for the pion-exchange induced mechanism of $\Delta$ production and provides a constraint on the $\pi N \Delta$ form factor. The production of leading pions in proton-proton collisions puts additional constraints on the $\pi NN$ vertex form factors. All these constraints are used then to estimate the pion content of the nucleon and allow to calculate parameter-free the x-dependence of $\bar d - \bar u$. We discuss the violation of the Gottfried Sum Rule and $\bar d$-$\bar u$ asymmetry and compare to the one obtained from the E866 experiment at Fermilab.


In this paper, we aim to develop a new type of neutrosophic crisp set called the retract neutrosophic crisp set and shows a grayscale image in a 2D Cartesian domain with neutrosophic crisp components in the neutrosophic domain. The introduced set is a retraction of any triple structured crisp set. Whereas, the retractset deduced from any neutrosophic crisp set is coincide its corresponding star neutrosophic crisp set defined in by Salama et al. [1]. Hence we construct a new type of neutrosophic crisp topological spaces, called the retract neutrosophic crisp topological space as a retraction of the star neutrosophic topological space. Moreover, we investigate some of its properties.


A scientific approach to meticulously examine the significance of warranty as a key marketing tool to promote sales of goods by virtue of warranty length optimization, which presumably results into an increase in the overall profit for an organization is proposed. Understanding warranty from customer's perspective, we can construe that, a customer indubitably considers it to be an "implied warranty" i.e. a formal commitment of the seller, which entrusts certain responsibilities on the manufacturer towards product quality for ensuring product performance after sales safe-guarding the end user's expectations and interest. The two models presented in this paper cater to two different scenarios: (1) longer warranty period to increase marketability and in creating goodwill for the manufacturer and sacrificing on the overall profit, (2) shorter warranty period ensuring improved profitability for the manufacturer. Exponential distribution is used to represent the lifetime of a product. Two numerical illustrations demonstrate applications of the models and their comparison.


In situ real-time x-ray diffraction was used to study temperature-induced structural changes of 1–5 nm Au, Pt, and AuPt nanocatalysts supported on silicon substrates. Synchrotron-based x-ray diffraction indicates that the as-synthesized Au and Au64Pt36 nanoparticles have a non-crystalline structure, while the Pt nanoparticles have the expected cubic structure. The nanoparticles undergo dramatic structural changes at temperatures as low as 120 °C. During low-temperature annealing, the Au and AuPt nanoparticles first melt and then immediately coalesce to form 4–5 nm crystalline structures. The Pt nanoparticles also aggregate but with limited intermediate melting. The detailed mechanisms of nucleation and growth, though, are quite different for the three types of nanoparticles. Most interestingly, solidification of high-density AuPt nanoparticles involves an unusual transient morphological transformation that affects only the surface of the particles. AuPt nanoparticles on silicon undergo partial phase segregation only upon annealing at extremely high temperatures (800 °C).


It was found that the affinity of a monoclonal antibody directed against a recombinantly expressed HIV-1 capsid protein p24 (rp24) strongly increased after chemical modification of the Iysine residues of rp24 with different amounts of maleic anhydride. The extent and the sites of modification were analyzed by MALDI-TOF mass spectrometry. Unmodified rp24 and the differently modified rp24 samples were tested for binding the murine monoclonal antibody CB4-1 which recognizes the epitope GATPQDLNTML comprising residues 46-56 of rp24. An increase in the number of modified lysine residues led to enhanced binding affinity of CB4-1. Most pronounced effects were observed after substitution of the first amino groups: an average number of three modified residues per protein molecule increases the binding affinity by a factor of 23, but the substitution of the remaining nine residues increases the binding affinity only by a factor of 11. Fully modified rp24 variant proteins were bound by CB4-1 with Kd values comparable to that of the peptide epitope. Conformation and stability of the unmodified rp24, highly (rp24F, 9 residues; rp24G, 11 residues) modified, and fully modified protein (rp24I, 11 lysine residues and N-terminus) were analyzed by circular dichroism (CD) and fluorescence spectroscopy under different solvent conditions. Little difference in conformation and unfolding behavior was observed between the unmodified and highly modified rp24, which differ drastically in the antibody binding behavior. The fully modified sample, however, displayed a significant decrease in alpha-helical content. Thus, the epitope seems to be hidden (cryptotope) in the unmodified rp24 in a low-affinity binding conformation and becomes displayed at low levels of chemical modification which obviously induce subtle structural changes prior to changes of the overall folding observable by spectroscopic means.


Hepatocellular carcinoma (HCC) is the most common primary liver malignant tumor, and the targeted therapy for HCC is very limited. Our previous study demonstrated that prodigiosin(PG), a secondary metabolite from Serratia marcescens found in the intestinal flora of cockroaches, inhibits the proliferation of HCC and increases the expression of CHOP, a marker protein for endoplasmic reticulum stress (ERS)-mediated apoptosis, in a dose-dependent manner. However, the mechanisms underlying the activity of PG in vivo and in vitro are unclear. This study explored the molecular mechanisms of PG-induced ERS against liver cancer in vitro and in vivo. The apoptosis of hepatocellular carcinoma cells induced by PG through endoplasmic reticulum stress was observed by flow cytometry, colony formation assay, cell viability assay, immunoblot analysis, and TUNEL assay. The localization of PG in cells was observed using laser confocal fluorescence microscopy. Flow cytometry was used to detect the intracellular Ca2+ concentration after PG treatment. We found that PG could promote apoptosis and inhibit the proliferation of HCC. It was localized in the endoplasmic reticulum of HepG2 cells, where it induces the release of Ca2+. PG also upregulated the expression of key unfolded response proteins, including PERK, IRE1α, Bip, and CHOP, and related apoptotic proteins, including caspase3, caspase9, and Bax, but down-regulated the expression of anti-apoptotic protein Bcl-2 in liver cancer. Alleviating ERS reversed the above phenomenon. PG had no obvious negative effects on the functioning of the liver, kidney, and other main organs in nude mice, but the growth of liver cancer cells was inhibited by inducing ERS in vivo. The findings of this study showed that PG promotes apoptosis of HCC by inducing ERS.


A major concern in distributed networks is the ability to provide acceptable levels of security. This is achieved by using encryption and authentication mechanisms that depend on encryption keys. However, given the ever-expanding nature of the network, it is difficult to keep setting up authorities that can aid the key- exchange process. This paper presents a novel solution to the challenge of exchanging keys of a large, distributed network without the need to set up additional authorities. The key-exchange scheme presented takes advantage of features such as packet anonymity, random selection and a multi- path approach for the exchange process. The paper also discusses the effectiveness of the proposed scheme against various threat scenarios.


The case of soil contamination by heavy metals in environment shows an increasing amount along with the constructions and development period that has been done. The identification of heavy metal content in the field is extremely hard to be done without a laboratory activity. Therefore, it needs a quick and non-destructive approach or method to identify the metal content of the soil in the field. The application of Near Infrared Reflectance Spectroscopy (NIRs) technology is a method that non-destructively able to detect the heavy metal content in the soil by using Partial Least Square Regression (PLSR). Pretreatment spectrum which is done using the Multiplicative Scatter Correction (MSC) can improve the results of the prediction models of PLSR. The results of MSC pretreatment spectrum can repair and improve the accuracy of the predictions of Lead (Pb) and Zinc (Zn) in the soil. Eight samples were used for analysis of each of Pb and Zn content. The measured data were pre-treated by MSC. It was obtained that value of r = 0.98, R 2 = 0.97 and RPD = 6.46 for the Pb content measurement. Meanwhile, the measurement for Zn obtained the value of r = 0.98, R 2 = 0.97 and RPD = 6.28. Therefore, it can be inferred that the NIRs is one of technologies which is worth reckoned as the right and quick means to predict the content of heavy metals in soil in a non-destructively and environmentally friendly way.


Correspondence: Dr. Sameer Neupane, MD Department of Pathology, B. P Koirala Memorial Cancer Hospital, Bharatpur, Nepal Primary carcinosarcoma of the lung is exceedingly rare. It is described as malignancy composed of a mixture of carcinoma and sarcoma elements. The sarcomatous element is usually spindle cell but may contain cartilage, bone or skeletal muscle. We report a case of pulmonary carcinosarcoma in a 66 years male who presented with cough, chest pain on exertion, anorexia and weight loss. Brush cytology revealed poorly differentiated non-small cell carcinoma. Histopathological examination showed proliferation of malignant spindle cells containing bone and malignant cartilage admixed with areas of keratinized squamous cells with few foci of ill-defi ned glandular structure. On immunohistochemistry, carcinomatous component of tumor showed positivity for cytokeratin AE1/AE3 and spindle cell component were positive for vimentin. These fi ndings led to diagnosis of carcinosarcoma. ABSTRACT


Patients with renal failure and undergoing a cadaver renal transplant were found to have plasma concentrations of laudanosine, following the administration of a single bolus dose of atracurium 0.5 mg kg-1, higher than those found in patients without renal failure. Since laudanosine is a known central nervous system stimulant in a variety of animal species, its actions should be investigated further in man, and particularly in patients with renal failure.


Brattle-Boro type rats with average weight of 200 gms were used for the experiment. We established 5 groups with 10 rats in each. Group I was the control group, Group II pancreatic trauma group and Group III rats were the pancreatitis group induced by 50% alcohol. Groups IV and V were the groups in which Octreotide was injected in different time intervals after induction of pancreatitis by 50% alcohol. Amylase values were statistically significant between the control group in which Octreotide was injected in different time intervals after induction of pancreatitis by 50% alcohol. The amylase values were statistically significant between the control group and the experiments (t2 = 4.69 p < 0.001, t3 = 8.06 p < 0.00001, t4 = 4.23 p < 0.002, t5 = 4.3 p < 0.002), and it was also significant between Group III and Groups II, IV, V (t2 = 9.62 p < 0.0001, t4 = 10.26 p < 0.0001, t5 = 3.69 p < 0.005), but it was not found significant between Groups II and IV, V (t4 = 0.52 p < 0.6, t5 = 1.69 p < 0.1). Histopathologic examination of the trauma group showed congestion, minimal lymphomonocyte infiltration. Patchy necrosis and shrinkage of the acinar cells with ductal dilatation were seen in the SMS 201-995 injection groups which were more pronounced in Group V. As a conclusion SMS 201-995 is not effective to prevent the ongoing pathology of pancreatitis but the increasing values of amylase were limited on the level of simply induced traumatic pancreatitis. It may be useful in the suppression of the enzymatic production during the course of pancreatitis.


One of the important design considerations in modern watercooled nuclear reactors is their thermal performance during hypothetical accident situations. However, an accurate analysis of the system thermal-hydraulics is required before the thermal margins can be appraised. An analysis based on the method of characteristics has been developed by which the exact solution to flow decay transients in homogeneous two-phase systems can be obtained. The exact solution presented yields the system flow and quality at each point in space and time during an exponential flow decay transient. These parameters can then be combined with an appropriate critical heat flux (CHF) correlation to predict the occurrence of transient CHF. (auth)


Over the last decade, structure–function relationships have begun to encompass networks of brain areas rather than individual structures. For example, corticostriatal circuits have been associated with sensorimotor, limbic, and cognitive information processing, and damage to these circuits has been shown to produce unique behavioral outcomes in Autism, Parkinson's Disease, Schizophrenia and healthy ageing. However, it remains an open question how abnormal or absent connectivity can be detected at the individual level. Here, we provide a method for clustering gross morphological structures into subregions with unique functional connectivity fingerprints, and generate network probability maps usable as a baseline to compare individual cases against. We used connectivity metrics derived from resting‐state fMRI (N = 100), in conjunction with hierarchical clustering methods, to parcellate the striatum into functionally distinct clusters. We identified three highly reproducible striatal subregions, across both hemispheres and in an independent replication dataset (N = 100) (dice‐similarity values 0.40–1.00). Each striatal seed region resulted in a highly reproducible distinct connectivity fingerprint: the putamen showed predominant connectivity with cortical and cerebellar sensorimotor and language processing areas; the ventromedial striatum cluster had a distinct limbic connectivity pattern; the caudate showed predominant connectivity with the thalamus, frontal and occipital areas, and the cerebellum. Our corticostriatal probability maps agree with existing connectivity data in humans and non‐human primates, and showed a high degree of replication. We believe that these maps offer an efficient tool to further advance hypothesis driven research and provide important guidance when investigating deviant connectivity in neurological patient populations suffering from e.g., stroke or cerebral palsy. Hum Brain Mapp 38:1478–1491, 2017. © 2016 Wiley Periodicals, Inc.


Although historians recognize Deborah Franklin's abilities and accomplishments, she invariably suffers in comparison with her famous husband. She seems to have shared the fate of Anne Bradstreet a century earlier, whose worldly spouse, Simon, for years remained object of his wife's tender affection and dutiful supervision of his affairs. The article attempts to examine and evaluate Mrs. Franklin's immeasurable contribution to the Franklin household and business, which enabled Benjamin to act on the international arena and indulge in the frivolities of the contemporary high life, against his egalitarian declarations.


arbitrary, but it will be complemented by a second volume which should include dislocations, patterns in dendrites, and the properties of ionic crystal surfaces. For anyone wanting to come to terms with current theories for crystal growth, the book is an excellent starting-point for each of the selected topics. However, it should be stressed that the reader will need a strong stomach for mathematics. Applications of the theories to real, rather than model, systems are rare. Specific test examples include the melting of graphite intercalation compounds, and mercury chain compounds. With such a flavour it is likely that the book will appeal more to physical chemists rather than earth scientists. Despite these drawbacks it should still be useful as a reference book for mineralogists concerned with the fundamental details of crystal growth mechanisms. R. FREER


In O+OB close binary systems, a secular motion of the apsides arises from orbital perturbations due to superior order momenta of the gravitational classical potential and general relativity effects. This phenomenon and theoretical stellar structure models, can be used to estimate absolute masses of the system components, even for non-eclipsing binaries. This project aims to establish the feasibility of this mass determination method in all the massive close binary stars for which it could be applied. In this work we briefly describe the selection criteria of the systems to be studied, the sampling status of their radial velocity curves, the adopted procedures for spectroscopic data reduction, and few preliminary results.


A rich model based motion vector steganalysis benefiting from both temporal and spatial correlations of motion vectors is proposed in this work. The proposed steganalysis method has a substantially superior detection accuracy than the previous methods, even the targeted ones. The improvement in detection accuracy lies in several novel approaches introduced in this work. Firstly, it is shown that there is a strong correlation, not only spatially but also temporally, among neighbouring motion vectors for longer distances. Therefore, temporal motion vector dependency along side the spatial dependency is utilized for rigorous motion vector steganalysis. Secondly, unlike the filters previously used, which were heuristically designed against a specific motion vector steganography, a diverse set of many filters which can capture aberrations introduced by various motion vector steganography methods is used. The variety and also the number of the filter kernels are substantially more than that of used in previous ones. Besides that, filters up to fifth order are employed whereas the previous methods use at most second order filters. As a result of these, the proposed system captures various decorrelations in a wide spatio-temporal range and provides a better cover model. The proposed method is tested against the most prominent motion vector steganalysis and steganography methods. To the best knowledge of the authors, the experiments section has the most comprehensive tests in motion vector steganalysis field including five stego and seven steganalysis methods. Test results show that the proposed method yields around 20% detection accuracy increase in low payloads and 5% in higher payloads.


The Pandemic situation caused due to SARS-CoV-2 causing Coronavirus Disease (CoVID-19) around globe. Recent, COVID-19 main protease complex (Mpro), highly modulating enzyme in SARS-CoV-2 was reported for viral replication and transcription. This multifunctionality of Mpro attracts for identification of potential drug target. Considering impact, In silico analysis was performed for Palmatine alkaloid against Mpro. Naturally, present in Tinospora cordifolia, found effective against Cancer, HIV, viral infections, diabetics. In methods, physico-chemical analysis by ProtParam tool and Structure of Mpro was predicted by SWISS-MODEL Workspace homology modeling server. Superimposition Structure and significant equal QMQE, QSQE values were found for eight highly similar templates. Structural assessment validation by Ramachandran plot (97.67% favoured), Local Quality estimate ratio (>0.6) and higher QMEAN score (y-axis). Further, docking was performed with validated Mpro model by SwissDock server. Interaction with -8.281919 ΔG indicates reliable Interaction. Also, comparative docking reveals, most favoured Palmatine interaction. Thus, an attempt was made to find potent inhibitor for SARS-CoV-2, as there is no promising and specific anti-viral drug or vaccine available for prevention and treatment of infections. However, In Vitro studies are required. Toxicity studies reported against Palmatine for acute effect (135 mg/kg body weight) on mouse model LD 50.


The tumor stroma performs an important role in carcinogenesis. It predominantly consists of fibroblasts and the connective tissue produced by them, and undergoes a multitude of interactions with the surrounding cancer cells. Since irradiation is part of the majority of therapeutic strategies for head and neck squamous cell carcinoma, more information regarding the effects of a previous irradiation on the tumor stroma is desirable. In the present study, fibroblasts were cultivated from human non-irradiated and pre-irradiated skin of the neck for 48 h. Subsequently, analyses of cell viability, apoptosis, necrosis and motility were conducted via MTT assay, Annexin V/propidium iodide staining, electronic cell counting for 4 consecutive days, and scratch assay. Pre-irradiated fibroblasts exhibited a significantly slower growth rate as well as increased rates of apoptosis and necrosis. They also exhibited significantly decreased motility compared with non-irradiated fibroblasts. These results indicated the long-term effects of irradiation on fibroblasts, which may affect cancer recurrence in the irradiated region via the tumor stroma. More information, such as that regarding the secretory capacities of pre-irradiated fibroblasts, is required to evaluate the possible therapeutic implications of these findings.


Gastropexy is a surgical technique performed to prevent and decrease the recurrence rate of gastric dilatation and volvulus (GDV). The objective of this prospective, a descriptive cohort study on 100 client-owned dogs who were presented with GDV, is to describe a modified belt-loop gastropexy and determine its intraoperative complications and long-term efficacy. The transversus abdominis muscle was used to make an oblique belt-loop. A seromuscular antral fold, instead of a seromuscular antral flap, was passed through the belt-loop, and then, the passed portion of the antral fold was sutured to the dissected edge of the abdominal wall. Intraoperative complications related to gastropexy were recorded, and the incidence of GDV recurrence was determined a minimum of 1 yr postoperatively via telephone with the referring veterinarians and the owners. There were no intraoperative complications related to the modified belt-loop gastropexy technique. Based on follow-up conversations, none of the dogs presented signs of GDV recurrence during the follow-up period. Based on the results, there is strong clinical evidence that a modified belt-loop gastropexy prevents recurrence of GDV in dogs surviving an acute episode.


Since the original descriptions by Tay in 1881 and Sachs in 1887 of amaurotic familial idiocy in infants, a great deal of knowledge has been added to the subject, and it is now recognized that this condition exists not only in the form of ( a ) infantile amaurotic familial idiocy as originally described but in three additional forms, namely ( b ) the late infantile type, ( c ) the juvenile type and ( d ) the adult type. 1 As the cases reported in this paper are instances of the classic form of amaurotic familial idiocy, to which the name Tay-Sachs disease has been given, a brief description of the disease will be limited to this form only and the others will be omitted as being beyond the scope of this presentation. Tay-Sachs disease is uncommon, though not rare; and while cases have been reported for the past fifty years, a search of the literature available


Abstract : The creation and implementation of The Landing Ship Tank brought amphibious operations to a new level of significance in the U.S military during WWII. Without its introduction during the war, many operations such as the landing at Normandy or the island hopping of the Pacific, would have been delayed or not conducted and could very well have cost the US victory during these conflicts. Presented in this thesis is a review of amphibious warfare development in the interwar period to include the aspects of doctrine and tactics, types of landing craft and ships that were used by the U.S. Military. It also examined the training exercises and the equipment that were available to the U.S. military in the interwar period. Further, the study conducts an analysis of the technological innovations that were introduced because of the operational requirements for the LST and the way in which they were employed in theater. This thesis looks at the evolution of the LST from its initial conception to the end of WWII in 1945. The study finds that the LST performed a vital service to the U.S. and its Allies during WWII and it changed how the U.S. military conducted amphibious operations on a tactical and operational level. It also shows that the LST did not impact published amphibious warfare doctrine. A historical understanding of this ship and the influence it had on major operations during WWII can provide insight for future naval leaders and policy makers in the design and employment of innovative new amphibious ships.


ABSTRACT Warm dense matter is a peculiar state with solid densities and temperatures 1 − 100 eV. Its ab initio description waits united efforts of quantum chemistry, condensed matter and plasma physics. We use the finite temperature Kohn–Sham density functional theory (a 'workhorse' in this field) to study the pressure build-up with increase of electronic temperature in crystal and amorphous warm dense matter (WDM) gold. We compare the ab initio results with the effective ion–ion interaction model and reveal the possibility to separate the free electron contribution to the total pressure in WDM and to determine the corresponding degree of ionisation. For the sake of clarity, we try to describe our findings using the proper framework of statistical physics and briefly review the free energy models for WDM.


The Plutonium Protection System (PPS) is an integrated safeguards system developed by Sandia Laboratories for the Department of Energy, Office of Safeguards and Security. The system is designed to demonstrate and test concepts for the improved safeguarding of plutonium. Volume 2 of the PPS final report describes the hardware elements of the system. The major areas containing hardware elements are the vault, where plutonium is stored, the packaging room, where plutonium is packaged into Container Modules, the Security Operations Center, which controls movement of personnel, the Material Accountability Center, which maintains the system data base, and the Material Operations Center, which monitors the operating procedures in the system. References are made to documents in which details of the hardware items can be found.


Rho family GTPases are ideal candidates to regulate aspects of cytoskeletal dynamics downstream of axon guidance receptors. To examine the in vivo role of Rho GTPases in midline guidance, dominant negative (dn) and constitutively active (ct) forms of Rho, Drac1, and Dcdc42 are expressed in the Drosophila CNS. When expressed alone, only ctDrac and ctDcdc42 cause axons in the pCC/MP2 pathway to cross the midline inappropriately. Heterozygous loss of Roundabout enhances the ctDrac phenotype and causes errors in embryos expressing dnRho or ctRho. Homozygous loss of Son-of-Sevenless (Sos) also enhances the ctDrac phenotype and causes errors in embryos expressing either dnRho or dnDrac. CtRho suppresses the midline crossing errors caused by loss of Sos. CtDrac and ctDcdc42 phenotypes are suppressed by heterozygous loss of Profilin, but strongly enhanced by coexpression of constitutively active myosin light chain kinase (ctMLCK), which increases myosin II activity. Expression of ctMLCK also causes errors in embryos expressing either dnRho or ctRho. Our data confirm that Rho family GTPases are required for regulation of actin polymerization and/or myosin activity and that this is critical for the response of growth cones to midline repulsive signals. Midline repulsion appears to require down-regulation of Drac1 and Dcdc42 and activation of Rho.


Introduction The risk to health for workers exposed to silica is well established, however the number of workers exposed is less well known, particularly in developing economies. In order to successfully address the issue of exposure and its effects an accurate assessment of the problem is required. The emerging economies of Brazil, Russia, India, China and South Africa (BRICS) are major geopolitical entities with diverse industrial economies, acting as indicators of development in there respective geographical areas, making them ideal as a focal point on which assessments may be focused. Methods A narrative literature review was performed to provide information regarding the key industrial areas for exposure in each of the BRICS nations. Where available qualitative estimates on the key industries associated with silica exposure in each Nation were determined. Results Due to similarities in the economic and industrial landscape of the BRICS mining was the most common exposure cause, with high levels also seen in construction and manufacturing. Neither detailed nor approximate records of exposure where available from any of the Nations, although non-industry specific estimates could be accessed for each Nation with the exception of Russia, where very little published information was available. Conclusion Future efforts to reduce exposure are dependent on an accurate assessment and recording of exposure levels. Currently there is very little large-scale empirical data available from any of the Nations assessed though with the exception of Russia all of the Nations profiled have some publically available records through both academic research and governmental monitoring. From this review it is apparent that further work is required by industry and governments to provide and publish accurate data regarding silica exposure.


Thermal shock behavior of ceramics plays a decisive role in their broad industrial applications. For enhanced understanding of damage and failure mechanism under thermal shock loading, in the present work, a combination of experimental testing and numerical simulation methods has been used. The thermal shock behavior of the alumina (99.7%) disk samples has been investigated by using a plasma test stand: the bottom of the ceramic disks were locally heated in the center by plasma beam; during the heat treatment the temperature distribution at the top of the sample was recorded with a thermographic system. To characterize the thermal shock resistance, a thermomechanical simulation was subsequently carried out. It calculates the temperature and stress distribution within the ceramic disks. The calculated critical thermal tension stresses are reported, which led to the failure of the ceramic disks under thermal shock loading. The effect of the sample thickness on the temperature and stress distribution is presented. Compared with the experimental results the simulated results show excellent agreement. As conclusion, it is possible to determine the thermal shock behavior of ceramic materials by the combination of experimental testing and numerical simulation.


Abstract. Forest liming is a management tool that has and continues to be used
extensively across northern Europe to counteract acidification processes
from anthropogenic sulfur and nitrogen (N) deposition. In this study, we
quantified how liming affects soil organic carbon (SOC) stocks and attempt
to disentangle the mechanisms responsible for the often contrasting
processes that regulate net soil carbon (C) fluxes. Using a paired plot
experimental design we compared SOC stocks in limed plots with adjacent
unlimed control plots at 28 experimental sites to 60 cm soil depth in mature
broadleaf and coniferous forests across Germany. Historical soil data from a
subset of the paired experiment plots were analyzed to assess how SOC stocks
in both control and limed plots changed between 1990 and 2019. Overall, we found that forest floor C stocks have been accumulating over
time in the control plots. Liming however largely offset organic layer
buildup in the L/Of layer, and forest floor C stocks remained unchanged
over time in the limed plots. This, in turn, meant that nutrients remained
mobile and were not bound in soil organic matter complexes. Results from the
paired plot analysis showed that forest floor C stocks were significantly
lower in limed plots than the control (−34 %, −8.4 ± 1.7 Mg C ha−1) but did not significantly affect SOC stocks in the
mineral soil, when all sites are pooled together. In the forest floor
layers, SOC stocks exhibited an exponential decrease with increasing pH,
highlighting how lime-induced improvements in the biochemical environment
stimulate organic matter (OM) decomposition. Nevertheless, for both forest
floor and mineral soils, the magnitude and direction of the belowground C
changes hinged directly on the inherent site characteristics, namely, forest
type (conifer versus broadleaf), soil pH, soil texture, and the soil SOC
stocks. On the other hand, SOC stock decreases were often offset by other
processes that fostered C accumulation, such as improved forest productivity
or increased carbon stabilization, which correspondingly translated to an
overall variable response by SOC stocks, particularly in the mineral soil. Lastly, we measured soil carbon dioxide (CO2) and soil methane
(CH4) flux immediately after a re-liming event at three of the
experimental sites. Here, we found that (1) liming doubles CH4 uptake
in the long-term; (2) soil organic matter mineralization
processes respond quickly to liming, even though the duration and size of
the CO2 flush varied between sites; and (3) lime-derived CO2
contributed very little to total CO2 emissions over the measurement
period (determined using stable isotope approaches).


There have been significant advances in sorghum
research and considerable increases in world
sorghum grain production and yield in the past
decade. However, the sobering fact 1s that, with
the notable exception of India, there has been
only a minimal improvement in overall production
from the countries where sorghum is used
primarily in human food (Kanwar and Ryan 1976)
and indications are that production trends will be
negative before long in many countries (Ryan,
rsonal communication). This is a,slruation that
an be ignored only at our peril. It is a situation for v which something can be done, but only if we take
an objective look at our ideas-many of which are
preconceived. We must realize that the solutions
proposed and results obtained in the sorghum
research field in developed countries, must be
examined very critically before being adopted or
utilized as blueprints for attacking the serious and
urgent problems of increasing sorghum production,
particularly in Africa. I make no apology.
therefore, for 'slanting' my remarks today on
entomology, towards the developing world situation.
Even a brief scan of the sorghum literature
shows that the developed world is exceptionally
well catered for, both by the amount and quality of
information being produced on sorghum in all
scientific disciplines, including entomology.
However, I suspect that in the 10 years since the
last sorghum symposium, the number of research
nd development workers, who are able to devote b eir full time to the sorghum crop in Africa and
the developing world has not increased to anywhere
near the extent needed, to cope with the
well documented problems of feeding their rapidly
expanding populations. Indeed the number of
sorghum research workers in the developing
world may well have decreased!


This thesis is part of my own story and that of the people with whom I worked and researched in Tonga. The research paradigm is action research and both qualitative and quantitative techniques have been used to distil an understanding of education change in Tonga. In essence, there are cultural factors which make educational change difficult to enact and from an outsider's perspective this can be difficult to comprehend. From an insider's perspective, however, cultural identity and cultural roles have helped to define and articulate Tongan values and to describe who the Tongan people are. Culture has also provided a rich social network which has helped to sustain the Tongan people as they transition and interact with the wider world.
There are, therefore, elements of historical research (such as that by Campbell) and ethnographic research (such as that by Thaman) embedded in this semi-longitudinal study of education and leadership in Tonga through my work with teachers and school principals. This thesis, therefore, does not follow the traditional positivism model that is more linear in focus; rather it follows the action research paradigm that knowledge formation is iterative and that investigators need to explore the narrative and the discourse from a number of perspectives and over time.
In part, this action research study tells of my growing awareness that, if the people of one culture (in this case, Tongan) wish to make changes in a facet of its society, it is by no means assured that somebody outside that culture can contribute significantly and directly to that change.
In 2009, as a volunteer education consultant with an Australian non-government agency, I was invited by the head of the Free Wesleyan Church of Tonga Education System to 'improve' the classroom skills of its teachers and to design a five-year strategic plan for the System. So, the first major question I addressed is:
1. What changes might be suggested to the leaders of the Free Wesleyan Church of Tonga Education System which could enhance the quality of education in the System?
The answer starts with a description of Tonga – its geography and its history, its social and hierarchical structure and various facets of its culture, including two key facets, religion and education (Chapter 2, Part B). There is limited academic literature related to Tongan education but there are historical documents and policy statements to which reference is made throughout the thesis. This action research takes into account the experiences and understanding of the stakeholder teachers, school principals and education officers.
The description of Tonga is followed by an outline of my own experience during five, three-month visits which I made to the country over five years (Chapter 3, Part A). Among other things, this experience led me to conclude that the issues I had been encountering could be addressed in a descriptive research thesis.
During those visits, various aspects of Tongan culture were acting both for and against the so-called 'improvement' sought by the senior officers of the education system. Therefore, a second question emerged:
2. What cultural factors affect the degree to which changes are implemented?
A culturally appropriate process of ascertaining the desired knowledge and views was designed and carried out. Chapter 3, Parts B to E to and Chapter 4 explain the method and the results of this process which included interviews with nineteen education officers, school principals and deputy principals. The results include interview responses which demonstrated a deeper knowledge and understanding of the issues involved and an implied preparedness to be involved in the changes many of the interviewees regarded as desirable. Most of the telling comments were about attitudes, hierarchy, limited resources to implement change, leadership that was linked to Tongan values and an economy that struggled to sustain its people using Western criteria.
Thus, the final question I address in this thesis is:
3. What are the most realistic strategies for improvement and how might the System implement them?
Chapter 5 addresses this question. For the most part, the answers came from the leaders of the education system – the principals, the deputies, the education officers and the people who have cultural 'authority' to bring about change. A problem is that they are in a tension. Do they look to an education system that is modelled on Western values and expectations or do they keep with a Tongan education system which respects the past, hierarchy and traditional teaching methods focussed on drill and examinations? Tonga is in transition and the tensions of that transition are reflected in the voices of the participants in this action research study. It appears that schools are struggling to construct 'relevance' for their students, as more of them leave the kingdom for work and other opportunities in Australia, New Zealand and the USA.
The evidence from this study suggests that the solution to the teaching problems perceived by the education leaders in the Free Wesleyan Church of Tonga Education System lies within themselves. Outsiders have a role to play but it is, at best, a secondary one. The Western system cannot be imposed and Tongans are unlikely to accept a solution that is inconsistent with their values. Western ideas and resources may be offered to the Tongan education leaders but they are empowered to select from this array and, in the end, work together with a range of stakeholders to find the best fit that respects their values and provides opportunities for the future of their young people.


It was recently argued that SU(3) chains in the $p$-box symmetric irreducible representation (irrep) exhibit a "Haldane gap" when $p$ is a multiple of 3 and are otherwise gapless [Nucl. Phys. B $\boldsymbol{924}$, 508 (2017)]. We extend this argument to the self-conjugate irreps of SU(3) with $p$ columns of length 2 and $p$ columns of length 1 in the Young tableau ($p=1$ corresponding to the adjoint irrep), arguing that they are always gapped but have spontaneously broken parity symmetry for $p$ odd but not even.


Incorporating multiuser detection (MUD) at receivers in a Multihop Packet Radio or ad-hoc Network has the potential to drastically improve performance. In this work, possible improvements are investigated and it is suggested that the Channel Coding Theorem be used for accurate modeling of the radio channel. With this model, MUD is shown to be more beneficial to ad-hoc networks employing spread-spectrum signals and in this case, the single-hop throughput increases linearly with the number of packets received. The delay performance of a narrow-band system employing Spatial-Time Division Multiple Access (S-TDMA) for scheduling is considered. MUD is incorporated into previously-proposed scheduling methods and a new method is proposed for generating the S-TDMA schedule by exploiting the detector. By simulation, MUD is shown to provide shorter length schedules, with the proposed method outperforming a systematic search. These results show that MUD typically provides a 20% reduction in the S-TDMA frame length, and thus decreases delay at low loads.


Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC

Myeloid cells localize to invasive edges of solid tumors where they promote invasive tumor growth, intravasation into vasculature and metastasis of malignant cells1,2. Fibroblasts, on the other hand, lead collective cell migration3 of carcinoma cells via fostering extracellular matrix (ECM) remodeling and generating tracks of collagen fibers that act as "highways" for cell migration4,5. To identify soluble molecules mediating these juxtacrine communication mechanisms between myeloid cells and fibroblasts in potentiating metastasis, we conducted pilot studies with subsets of spleen- or tumor-derived myeloid cells, tumor-derived fibroblasts, and mammary adenocarcinoma cells. Whereas spleen-derived CD11b+Ly6ChiLy6G− monocytes promote fibroblast migration ex vivo, two populations of tumor-derived myeloid cells, e.g., CD11b+Gr1+ and CD11b+Gr1− cells possessed this capability. In ex vivo migration assays, fibroblast migration was dependent on myeloid cell-derived factors, e.g., CXCL11, CXCL15, FGF2, IGF-1 and Shh, as well as fibroblast Akt and ERK1/2 phosphorylation. Inhibition of fibroblast MEK reduced myeloid cell-induced fibroblast migration, whereas FGF-RI inhibition completely abolished this capability. These studies indicate a role for myeloid cell-fibroblast communication in fostering migration (and potentially activation) of fibroblasts that lead collective cell migration properties of mammary carcinoma cells. Ongoing studies are identifying specific subpopulations of tumor-associated myeloid cells possessing these activities, as well as the role of FGF receptor signaling pathways in facilitating metastasis.

1.

Wyckoff, J.B., et al. Direct visualization of macrophage-assisted tumor cell intravasation in mammary tumors. Cancer Res 67, 2649-2656 (2007).

2.

Qian, B.Z. & Pollard, J.W. Macrophage diversity enhances tumor progression and metastasis. Cell 141, 39-51 (2010).

3.

Friedl, P., Locker, J., Sahai, E. & Segall, J.E. Classifying collective cancer cell invasion. Nat Cell Biol 14, 777-783 (2012).

4.

Khalil, A.A. & Friedl, P. Determinants of leader cells in collective cell migration. Integr Biol (Camb) 2, 568-574 (2010).

5.

Gritsenko, P.G., Ilina, O. & Friedl, P. Interstitial guidance of cancer invasion. J Pathol 226, 185-199 (2012).

The authors acknowledge generous support from the NIH/NCI, a Dept of Defense (DoD) Breast Cancer Research Program Postdoctoral Fellowship, a DoD Era of Hope Scholar Expansion Award, Susan G. Komen Fndt, and the Breast Cancer Research Fndt.

Citation Format: Aubie K. Shaw, Sergey Novitskiy, Lisa M. Coussens, Harold L. Moses. Myeloid cells promote fibroblast invasion and lead mammary adenocarcinoma cell invasion. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2301. doi:10.1158/1538-7445.AM2013-2301


This paper presents our vision for Evasive Internet, where destinations are only reachable through capabilities, which serve as hosts' flat transient addresses. Just as today's host addresses, our capabilities are obtained from the DNS hierarchy, thus never exposing destinations themselves to unprotected traffic. Our design supports in-network authentication of transient addresses and attribution of traffic they generate; our design further gives hosts full control over incoming flows. We achieve these objectives without exposing hosts to unprotected capability request traffic and without distributed filtering infrastructure. While significant work is needed to flesh out our vision, we hope it will contribute to improving security in future networks.


A biomechanical variable of interest to cyclists and cycling coaches is postural stability. A cyclist's position on a bicycle can be easily measured in a laboratory environment using motion capture software, but is difficult to measure in the field. The focus of this paper was to identify the legitimacy of a sacrum mounted triaxial accelerometer to identify temporal acceleration magnitudes of the centre of mass (CoM) whilst cycling against a motion analysis system. To provide validation of the sensor, data was collected at the torso as cyclists pedaled at varied cadences against a motion analysis system. The effects of cycling cadence and changes to torso angle via changes to hand position revealed that wearable technology (accelerometers) provide legitimacy in the assessment of torso accelerations during cycling. The minimal variation and change in agreement between the two systems during cycling indicates the adherence method of the accelerometer was suitable.


OBJECTIVE
To examine the diagnosis and treatment of arteriovenous malformations in adults, because of the tendency of the condition to recur.

DESIGN
Chart and literature review.

SETTING
Three tertiary-care hospitals.

PATIENTS
Twelve adults with diffuse arteriovenous malformations of the extremities.

INTERVENTIONS
Surgery of embolotherapy.

MAIN OUTCOME MEASURE
Recurrence.

RESULTS
Of the 12 cases reviewed, the arteriovenous malformations recurred in 8 patients; 2 of these were well, 6 months and 2 years after a second or third treatment. Two others were well, 2 months and 5 years after surgery or embolotherapy. One pregnant woman, whose case is described in detail, received no treatment, and her arteriovenous malformation diminished in size after her child was born. The outcome in the last patient is unknown.

CONCLUSION
Diffuse arteriovenous malformations recur after ablative treatment.


Although we have an immense scholarly literature on the arts, education, and certain aspects of cultural policy in the Soviet Union, it remains difficult to find this material synthesized into a single convenient volume. A group of German scholars has recently sought to remedy the deficiency with a collection of extended essays, and the effort is remarkable, not least because it does achieve synthesis despite the involvement of seven authors. A guiding conception is needed to achieve this synthesis, and it is set forth with admirable clarity in the introduction by Karl-Heinz Ruffmann. He penetratingly notes both the problem of cultural backwardness and the seriousness with which a new postrevolutionary Bolshevik leadership regarded that problem. There is a difference between accepting a given ideological position and acknowledging the commitment of others to it; and Ruffmann's way of treating Leninist perceptions of cultural issues—by giving full credence to the seriousness of the Bolshevik approach to these problems—avoids distortions commonly resulting when observers stand resolutely outside their subject and rely upon implicit antagonism rather than explicit criticism. All the contributors to the book are worthy of mention. The opening, and by far the longest, contribution is Oskar Anweiler's study of educational policy. This is followed by Klaus Meyer's treatment of science policy, Peter Hiibner's review of policy toward literature, and Hans-Jiirgen Drengenberg's study of policy toward the arts. The two concluding sections, on somewhat more unusual topics, are Bernhard Dilger's examination of national and minority cultures in the USSR and Wolfgang Kasack's survey of Soviet cultural policies in international relations. The omission of religion as a topic is explained by lack of space for an aspect of "negative cultural policy"; the slighting of the performing arts is not explained. Most of the contributors base the surveys offered in this volume on earlier and more detailed original research. But the fact that their contributions are surveys in no way diminishes the value of the book. Given the informing conceptualization that unifies the different parts, the volume provides a synthesis that undoubtedly exceeds the capabilities of any single scholar, and it illuminates, in comparative perspective, a vast range of vitally important policies that have unfolded since the Bolshevik seizure of power.


Palatine grafts, which today represent the simplest and most reliable technique for enhancing the adherent gum--a problem of great importance in periodontal treatment--are discussed together with other techniques designed for the same purpose. Bone site palatine grafts which restore adherent gum on the alveolar bone, are distinguished from osteo-dental site grafts which are proposed for the treatment of split gums and which only take partially on the radicular surface.


Herein, we report light-promoted photo/hydrogen atom transfer dual catalysis for arylsilylation of alkenes via the radical-radical cross-coupling with diverse hydrosilanes, which provides a simple and efficient method to prepare various organosilicon compounds with a wide range of substrate scope and good functional group tolerance under transition-metal- and chemical-oxidant-free conditions. Furthermore, the arylsilylation of alkenes can also proceed via the possible electron donor-acceptor complex under exogenous photocatalyst-free conditions.


The role of diet in rheumatoid arthritis (RA) has been the topic of extensive research. The present review aimed to present and appraise the studies assessing adherence to the Mediterranean diet (MD) and the primary/secondary prevention of rheumatoid arthritis. Based on the available studies, the evidence appears low and adherence to the MD does not appear to affect RA indices.


Health Care embraces a multitude of "services provided to individuals or communities by agents of the health services or professions, for the purpose of promoting, maintaining, monitoring, or restoring health." Health services meet the needs of entire population; cover the full range of Preventive, Curative and Rehabilitative services, as part of the basic social services of a country. India has a population of over 1.2 billion with 28 states and 9 Union Territories. Central government formulates comprehensive health policies and plans under the direction of the Ministry of Health and Family Welfare for items of national importance, including disease control, medical education, the medical profession, and state budgets, are the shared responsibility of the central government and individual states. Public health sector consist of Primary Health Care (Provided at Sub centre) Secondary Health Care (Provided at PHC, CHC, DH) Tertiary Health Care (Provided at large hospitals).
Public health sector is multifaceted various types of providers practicing in different systems of medicine, within different ownership structures. Individual states are given primary authority over most aspects of healthcare. An estimated 80% of public healthcare funding comes from the states. In-patient hospitalisation expenditure in India increased to 300% in last 10yrs in which more than 80% of expenditure met by OOPE, which leads to nearly 6million families getting into poverty due to catastrophic health expenditure. This led Government of India to launch Ayushman Bharat on 23 September 2018 with objective to cover over 10.74 crore poor and vulnerable families.
Biography:
Abhiruchi Galhotra is working as Additional Professor, Dept. of Community & Family Medicine, AIIMS, Raipur. Nodal Officer for ICMR funded Research Project on Prevalence & Etiology of Hearing Impairment. Post PG teaching experience
of 17 years. Supervisor for 2 PG theses. Contributed 5 chapters in various textbooks of which one is by Springer Nature and 2 others are by Springer. I also have more than 25 research publications to my credit which includes original articles, review articles, commentary, viewpoint and letter to editor.
Speaker Publications:
1. Bhat Ramesh (2006). Financial Health of Private sector hospitals in India.
2. Berman, P (2010). 'The Impoverishing effects of health Care payments in India: New methodology and findings'. Economic and Political weekly 27(16): 65-71.
3. Chaudhuri, A., and Roy, K. (2008). 'Changes in out-of-pocket payments for healthcare in Vietnam and its impact on equity in payments, 1992–2002'. Health Policy 88(1): 38–48
4. Economic Research Foundation (2006). Government health expenditure in India: a benchmark study. New Delhi.
5. National Commission on Macroeconomics and Health (2005). Financing and delivery of health care services in India.
5th World Congress on Public Health and Nutrition; London, UK- February 24-25, 2020.
Abstract Citation:
Abhiruchi Galhotra, A cross sectional study of utilization of sanitary facilities by adolescent girls in an urban slum of Raipur City, Chhattisgarh, India, Public Health 2020, 5th World Congress on Public Health and Nutrition; London, UK- February 24-25, 2020 (https://publichealth.healthconferences.org/abstract/2020/an-overview-of-health-care-system-in-india)


Acknowledgments Introduction 1. Social Accounts and Social Relations 1. A Simple Social Accounting Matrix 2. Implications of the Accounts 3. Disaggregating Effective Demand 4. A More Realistic SAM 5. Stock-Flow Relationships 6. A SAM and Asset Accounts for the United States 7. Further Thoughts 2. Prices and Distribution 1. Classical Macroeconomics 2. Classical Theories of Price and Distribution 3. Neoclassical Cost-Based Prices 4. Hat Calculus, Measuring Productivity Growth, and Full Employment Equilibrium 5. Mark-up Pricing in the Product Market 6. Efficiency Wages for Labor 7. New Keynesian Crosses and Methodological Reservations 8. First Looks at Inflation 3. Money, Interest, and Inflation 1. Money and Credit 2. Diverse Interest Theories 3. Interest Rate Cost-Push 4. Real Interest Rate Theory 5. The Ramsey Model 6. Dynamics on a Flying Trapeze 7. The Overlapping Generations Growth Model 8. Wicksell's Cumulative Process Inflation Model 9. More on Inflation Taxes 4. Effective Demand and Its Real and Financial Implications 1. The Commodity Market 2. Macro Adjustment via Forced Saving and Real Balance Effects 3. Real Balances, Input Substitution, and Money Wage Cuts 4. Liquidity Preference and Marginal Efficiency of Capital 5. Liquidity Preference, Fisher Arbitrage, and the Liquidity Trap 6. The System as a Whole 7. The IS/LM Model 8. Keynes and Friends on Financial Markets 9. Financial Markets and Investment 10. Consumption and Saving 11 "Disequilibrium" Macroeconomics 12. A Structuralist Synopsis 5. Short-Term Model Closure and Long-Term Growth 1. Model "Closures" in the Short Run 2. Graphical Representations and Supply-Driven Growth 3. Harrod, Robinson, and Related Stories 4. More Stable Demand-Determined Growth 6. Chicago Monetarism, New Classical Macroeconomics, and Mainstream Finance 1. Methodological Caveats 2. A Chicago Monetarist Model 3. A Cleaner Version of Monetarism 4. New Classical Spins 5. Dynamics of Government Debt 6. Ricardian Equivalence 7. The Business Cycle Conundrum 8. Cycles from the Supply Side 9. Optimal Behavior under Risk 10. Random Walk, Equity Premium, and the Modigliani-Miller Theorem 11. More on Modigliani-Miller 12. The Calculation Debate and Super-Rational Economics 7. Effective Demand and the Distributive Curve 1. Initial Observations 2. Inflation, Productivity Growth, and Distribution 3. Absorbing Productivity Growth 4. Effects of Expansionary Policy 5. Financial Extensions 6. Dynamics of the System 7. Comparative Dynamics 8. Open Economy Complications 8. Structuralist Finance and Money 1. Banking History and Institutions 2. Endogenous Finance 3. Endogenous Money via Bank Lending 4. Money Market Funds and the Level of Interest Rates 5. Business Debt and Growth in a Post-Keynesian World 6. New Keynesian Approaches to Financial Markets 9. A Genus of Cycles 1. Goodwin's Model 2. A Structuralist Goodwin Model 3. Evidence for the United States 4. A Contractionary Devaluation Cycle 5. An Inflation Expectations Cycle 6. Confidence and Multiplier 7. Minsky on Financial Cycles 8. Excess Capacity, Corporate Debt Burden, and a Cold Douche 9. Final Thoughts 10. Exchange Rate Complications 1. Accounting Conundrums 2. Determining Exchange Rates 3. Asset Prices, Expectations, and Exchange Rates 4. Commodity Arbitrage and Purchasing Power Parity 5. Portfolio Balance 6. Mundell-Fleming 7. IS/LM Comparative Statics 8. UIP and Dynamics 9. Open Economy Monetarism 10. Dornbusch 11. Other Theories of the Exchange Rate 12. A Developing Country Debt Cycle 13. Fencing in the Beast 11. Growth and Development Theories 1. New Growth Theories and Say's Law 2. Distribution and Growth 3. Models with Binding Resource or Sectoral Supply Constraints 4. Accounting for Growth 5. Other Perspectives 6. The Mainstream Policy Response 7. Where Theory Might Sensibly Go References Index


We demonstrate a new MMIC smart power amplifier, which consists of dual chain power amplifiers with a single matching network, the power added efficiency (PAE) of which, for 16 dBm output power, is as much as 21%, which represents more than a factor of three improvement of the PAE while satisfying all W-CDMA specifications. The power amplifier has been devised with two different parallel connected InGaP/GaAs HBT power amplifiers, each amplifier fitted to different a maximum power value: one to 17.5 dBm for low power mode and the other to 28 dBm for high power mode. The low power mode reveals -33 dBc of adjacent channel leakage power ratio (ACLR) at 16 dBm with 14 mA of quiescent current. The high power mode exhibits 40% of PAE and -30 dBc of ACLR at the maximum output power of 28 dBm.


Risk catalogs have proved to be an important instrument of preventive medicine for the identification of pregnancies at risk. Their purpose and usefulness is beyond all doubt. Nevertheless problems of principle are attached to them since they deflect the attention from the living reality of the individual case to statistically formed collectives. The importance of the problems for risk catalogs changes according to the social change and the constantly improved perinatal results. Age, parity and socioeconomic risks reflect such trends in development most clearly. Future tasks lie in the quantification of risks by differentiating the degrees of severity. A certain intrinsic dynamism of the present risk catalogs leads, e. g. to a constantly increasing incidence of sections. For this reason a constant feedback must exist between risk catalog and statistics.


We have employed a modified version of the LLNL Bounce-average Fokker-Planck code to model neutral beam-produced sloshing-ion equilibria in the TARA endplugs. The questions we have addressed concern the effect of deuterium beam operation as opposed to hydrogen operation, and the advantage of using full-energy beams rather than the usual three-component beams. We find that, for the expected "base case" TARA operating parameters, a 40% savings in required beam power is attained by using deuterium beams rather than hydrogen beams, and that the use of full-energy beams results in an additional 26% power savings for these parameters. For higher plasma temperatures the use of full-energy beams becomes significantly advantagous. We have also investigated the equilibria of two possible alternate mirror configurations for the TARA endplugs, believed to be more stable to trapped particle modes, and report those results here.


The process of ignition in aero-engines raises many practical issues that need to be faced during the design process. Recent experiments and simulations have provided detailed insights into ignition in single-injector configurations and on the light-round sequence in annular combustors. It was shown that large eddy simulation (LES) was able to reliably reproduce the physical phenomena involved in the ignition of both perfectly premixed and liquid spray flames. This study aims at further extending the knowledge on flame propagation during the ignition of annular multiple injector combustors by focusing the attention on the effects of heat losses, which have not been accounted for in numerical calculations before. This problem is examined by developing LESs of the light-round process with a fixed temperature at the solid boundaries. Calculations are carried out for a laboratory-scale annular system. Results are compared in terms of flame shape and light-round duration with available experiments and with an adiabatic LES serving as a reference. Wall heat losses lead to a significant reduction in the flame propagation velocity as observed experimentally. However, the LES underestimates this effect and leads to a globally shorter light-round. To better understand this discrepancy, the study focuses then on the analysis of the near wall region. An a priori analysis underlines the shortcomings associated with the chosen wall law by considering a more advanced wall model that fully accounts for variable thermophysical properties and for the unsteadiness of the boundary layer.


Composite materials especially glass fibre reinforced plastics (GFRP) are being widely used in many industry nowadays due to its special mechanical properties and light weight. The performance of composite materials is often
controlled by fibre volume fraction, V1. Hence, the main objective of this study is to investigate the effect of V1 onto the mechanical properties of composite plate. The
fibre used is chopped strand mat (CSM) type E-glass fibre where the matrix used is based on unsaturated polyester resin. The composite plates were prepared by hand lay-up technique. Rule of mixture (ROM) and modified rule of mixture (MROM)were used to predict the performance of the composite plates. Tensile test according to ASTM D 3039 was carried out to obtain ultimate strength and modulus of
elasticity of the composite plate with different V1. Three different composite systems were tested in this study. The actual Vj ofthe composite plates were justified by burn
out test (SIRIM MS 1390:1995). MROM was found had better validity than ROM to be used to estimate the mechanical properties of specimens after compared with experimental results. The experimental results show that the mechanical properties were improved when V1 is increased. Thus, the influence of fibre volume fraction on the mechanical properties of CSM E-glass fibre/polyester composites has been evaluated.


For simultaneous dimension reduction and variable selection for general regression models, including the multi-index model as a special case, we propose a penalized minimum average variance estimation method, combining the ideas of minimum average variance estimation in dimension reduction and regularization in variable selection. The resulting estimator can be found in a computationally efficient manner. Under mild conditions, the new method can consistently select all relevant predictors and has the oracle property. Simulations and a data example demonstrate the effectiveness and efficiency of the proposed method.


Clinical microbiology is a vast subject that covers a wide range of sub categories that include clinical bacteriology, clinical virology, clinical mycology, and clinical parasitology. The present book is a compilation of both research and review pieces related to the field of clinical bacteriology.


9-Methoxy-2-methylellipticinium acetate (6), along with the 9-methyl and 9-chloro derivatives (7, and 8, respectively) have shown remarkable selectivities in vitro against the NCI human CNS cancer subpanel. In order to target these types of compounds to the CNS in vivo, a series of 1,2-dihydroellipticines was synthesized. 9-Methoxy-2-methyl-1,2-dihydroellipticine (9) retained the potency and selectivity of the parent compound 6 but was unstable toward oxidation to 6. In order to improve the stability of 9, it was converted to the vinylogous amide 33 by introduction of a formyl group in the 4-position. Compound 33 proved to be much more stable than 9, but it was also less potent than 9 by about 1 order of magnitude, and it was less selective for the CNS subpanel than 9. To overcome the limited water solubilities of the ellipticines and dihydroellipticines, several ellipticine analogues incorporating polar groups on the N-2 nitrogen were prepared. The 2-(methoxymethyl)ellipticinium salts 24 and 25, as well as the (methylthio)methyl congener 26, were relatively potent anticancer agents which displayed cytotoxicity selectivity profiles similar to compound 6. The cytotoxic dihydroellipticines 9 and 10 exhibited potencies approaching that of ellipticine itself in facilitating the formation of a "cleavable complex", while the least cytotoxic ellipticine derivatives exhibited no cleavage above background.


For mobile robots moving in a plane, the mean square consensus problem is investigated under Markovian communication of partly known transition probabilities. Based on linear matrix inequalities, bisection search and numerical optimization, a design method is presented of feedback gains guaranteeing mean square consensus.


By using stoichiometric amounts of (C5H5)2FePF6, the isomeric neutral diamidate-bridged molecules, alpha- and beta-(DAniF)3Mo2(ArN(O)CC(O)NAr)Mo2(DAniF)3, with Ar = p-MeOC6H4, have been oxidized to give the PF6 salts of the four cations alpha1+, alpha2+, beta1+, and beta2+. All four structures have been accurately determined and, together with supporting evidence from near-IR, EPR, NMR and magnetic susceptibility measurements, it clearly establishes that in the mixed-valent alpha+ species the unpaired electron is localized over only one of the Mo2 units while the alpha2+ cation behaves as a diradical having two Mo25+ units that are essentially uncoupled. However, the beta+ species is fully delocalized, in the time scale of the experiments, with the unpaired electron being equally shared by the two Mo2 units. It displays a HOMO-1 --> SOMO transition at 4700 cm-1 (Deltanu1/2 = 2300 cm-1). Because of strong coupling, the beta2+ species is diamagnetic.


Purpose: OX40 agonist–based combinations are emerging as a novel avenue to improve the effectiveness of cancer immunotherapy. To better guide its clinical development, we characterized the role of the OX40 pathway in tumor-reactive immune cells. We also evaluated combining OX40 agonists with targeted therapy to combat resistance to cancer immunotherapy. Experimental Design: We utilized patient-derived tumor-infiltrating lymphocytes (TILs) and multiple preclinical models to determine the direct effect of anti-OX40 agonistic antibodies on tumor-reactive CD8+ T cells. We also evaluated the antitumor activity of an anti-OX40 antibody plus PI3Kβ inhibition in a transgenic murine melanoma model (Braf mutant, PTEN null), which spontaneously develops immunotherapy-resistant melanomas. Results: We observed elevated expression of OX40 in tumor-reactive CD8+ TILs upon encountering tumors; activation of OX40 signaling enhanced their cytotoxic function. OX40 agonist antibody improved the antitumor activity of CD8+ T cells and the generation of tumor-specific T-cell memory in vivo. Furthermore, combining anti-OX40 with GSK2636771, a PI3Kβ-selective inhibitor, delayed tumor growth and extended the survival of mice with PTEN-null melanomas. This combination treatment did not increase the number of TILs, but it instead significantly enhanced proliferation of CD8+ TILs and elevated the serum levels of CCL4, CXCL10, and IFNγ, which are mainly produced by memory and/or effector T cells. Conclusions: These results highlight a critical role of OX40 activation in potentiating the effector function of tumor-reactive CD8+ T cells and suggest further evaluation of OX40 agonist–based combinations in patients with immune-resistant tumors.


Tumor necrosis factor-α antagonists (TNFA) are associated with an increased risk of infections, including TB. Prior data showed that flow cytometric (FC) detection of co-expression of surface markers CD25(IL-2α receptor) and CD134(OX40) can identify antigen-specific effector CD4 + and CD8 + T-cell activation in LTBI. This diagnostic FC strategy has not been reported in active TB. A 18 year-old, US-born presented with 3 months of night sweats, abdominal pain, fever and cough. She received infliximab to treat ulcerative colitis for 2 years prior to presentation and had a negative tuberculous skin test. Chest CT revealed miliary pattern and lymphadenopathy. QuantiFERON-TB Gold in-Tube™ test was positive (2.62 IU/mL). Transbronchial lung biopsy and bronchoalveolar lavage showed acid-fast bacilli and culture showed pansensitive M. tuberculosis (MTB). Peripheral blood mononuclear cells were stimulated with specific MTB (RD1-peptides) and purified protein derivative (PPD) antigens and controls. Cells were marked with fluorescent antibodies to CD3, CD4, CD8, CD25 and OX40; 2x10 5 cells were analyzed. FC detection of CD25 + CD134 + co-expression in CD3 + CD4 + T-cells stimulated with RD1-peptides and PPD were 0.34% and 0.84%, respectively. Upregulation of CD25+CD134 on CD3 + CD8 + T-cells after stimulation with RD1-peptides and PPD were 0.26% and 0.59%, respectively. The FC assay results were within the positive thresholds for TB infection (Escalante P et al. AJRCCM, 2015). This new FC immune profiling strategy can detect antigen-specific T-cell activation in a patient with disseminated TB associated with TNFA. TNFA do not appear to cause false negative results to this test but further validation studies are warranted.


Chloritoid- and kyanite-bearing acid metavolcanic rocks of the Abitibi Greenstone belt have acquired an aluminum surplus by weathering prior to metamorphism. The weathering increases from the top of the volcanic unit downwards, as shown by increasing values for both Niggli-t and the Zr/P ratio. The depositional environment of these rocks is postulated to be either shallow marine or terrestrial.