The hyperglycemia and ketosis of diabetes mellitus are generally associated with elevated levels of glucagon in the blood. This suggests that glucagon is a contributing factor in the metabolic abnormalities of diabetes mellitus. A glucagon-receptor antagonist might provide important evidence for glucagons's role in this disease. In this work we describe how we combined structural modifications that led to glucagon analogues with partial agonist activity to give glucagon analogues that can act as competitive antagonists of glucagon-stimulated adenylate cyclase activity. Using solid-phase synthesis methodology and preparative reverse-phase high-performance liquid chromatography, we synthesized the following seven glucagon analogues and obtained them in high purity: [D-Phe4,Tyr5,Arg12]glucagon (2); [D-Phe4,Tyr5,Lys17,18]glucagon (3); [Phe1,Glu3,Lys17,18]glucagon (4); [Glu3,Val5,Lys17,18]glucagon (5); [Asp3,D-Phe4,Ser5,Lys17,18]glucagon (6); I4-[Asp3,D-Phe4,Ser5,Lys17,18]glucagon (7); [Pro3]glucagon (8). Purity was assessed by enzymatic total hydrolysis, by chymotryptic peptide mapping, and by reverse-phase high-performance liquid chromatography. The new analogues were tested for specific binding, for their effect on the adenylate cyclase activity in rat liver membranes, and for their effect on the blood glucose levels in normal rats relative to glucagon. Analogues showing no adenylate cyclase activity were examined for their ability to act as antagonists by displacing glucagon-stimulated adenylate cyclase dose-response curves to the right (higher concentrations). The binding potencies of the new analogues relative to glucagon (= 100) were respectively 1.0 (2), 1.3 (3), 3.8 (4), 0.4 (5), 1.3 (6), 5.3 (7), and 3 (8). Glucagon analogues 3-5 and 8 were all weak partial agonists with EC50 values of 500 (3), 250 (4), 1600 (5), and 395 nM (8), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Objectives: Postherpetic neuropathy (PHN) is common, severe, and often refractory to treatment. We treated 10 patients with refractory PHN using Scrambler therapy, a neurocutaneous stimulation device that delivers "nonpain" information with surface electrodes. Methods: Scrambler therapy was given as 30-minute sessions daily for 10 days. Pain was recorded before and after treatment. Two centers. Result: The average pain score rapidly diminished from 7.64 ± 1.46 at baseline to 0.42 ± 0.89 at 1 month, a 95% reduction, with continued relief at 2 and 3 months. Patients achieved maximum pain relief with less than 5 treatments. Discussion: Scrambler therapy appears to have a promising effect on PHN, with prompt and continued relief and no side effects. Further research is warranted.


Abstruct- A general technique to characterize asymmetric coplanar waveguide (CPW) discontinuities with air bridges where both the fundamental coplanar and slotline modes may be excited together is presented. First, the CPW discontinuity without air bridges is analyzed using the space-domain integral equation (SDIE) approach. Second, the parameters (phase, amplitude, and wavelength) of the coplanar and slotline modes are extracted from an amplitude modulated-like standing wave existing in the CPW feeding lines. Then a 2n x 2n generalized scattering matrix of the n-port discontinuity without air bridges is derived which includes the occurring mode conversion. Finally, this generalized scattering matrix is reduced to an n x n matrix by enforcing suitable conditions at the ports which correspond to the excited slotline mode. For the purpose of illustration, the method is applied to a shielded asymmetric short-end CPW shunt stub, the scattering parameters of which are compared with those of a symmetric one. Experiments are performed on both discontinuities and the results are in good agreement with theoretical data. The advantages of using air bridges in CPW circuits as opposed to bond wires are also discussed.


There is, from both a scientific and a practical point of view, an emerging interest in investigating the necessary conditions for creating new businesses. Perhaps one of the most important factors is the presence of an entrepreneurial university that both advances emerging areas of knowledge and puts this knowledge to use in developing the local region (Clark, 1998; Cooke, 2002). Therefore, has academic entrepreneurship been of high focus in spin-off creation both from the research (Lindholm, 1994; Feldman and Klofsten, 2000; Rickne, 2000) as well as from the practitioner viewpoint? Furthermore, to what extent has it resulted in the creation of various training programmes and incu- bators (Aaboen et al., 2008; Bergek and Norman, 2008)? A good practical example of the positive regional development effects of promoting entrepreneurship is the Entrepreneurship and New Business Development Programme (hereafter called the ENP) which is highlighted in this chapter. To understand the underlying structures and processes of entrepreneurial regional developments, this chapter addresses the use of academic entrepreneurship training, where coaching and mentoring are key tools to improve the quality and economic value of new spin-off firms.


Abstract Phenomenon Clinical teachers perform overlapping tasks in education and patient care. They are therefore expected to juggle many professional identities such as educator and clinician. Yet little is known about how clinical teachers negotiate their professional identities. The present research examined the lived experiences of clinical teachers as they manage and make sense of their professional identities in the context of a faculty development program. Approach This study adopted interpretative phenomenological analysis, which is an idiographic and inductive methodological approach that enables an in-depth examination of how people conceptualize their personal and social worlds. In-depth semi-structured individual interviews were conducted with six purposively sampled Brazilian clinical teachers who were attending a faculty development program. Each participant's lived experience was analyzed independently. Then, these individual analyses were compared against each other to identify convergence and divergence. Findings Participants recognized one identity, which was labeled as embedding identity, containing other identities and roles. Participants integrated their professional identities in agreement with their personal identities, values, and beliefs, striving thus for identity consonance. Participants understood their craft as a relational process by which they wove themselves into their context and entangled their experience with that of others. They, however, diverged when recognizing who their peers were; whereas some named a single professional group (i.e., family physicians), others had a more comprehensive view and considered as peers healthcare professionals, students, and even patients. Finally, participants identified time constraints and lower prestige of family medicine as a medical discipline vis-à-vis other specialties as challenges posed by their contexts. Insights Clinical teachers have multifaceted identities, to which they give a sense, manage, and integrate into their daily practice. Participants recognized an embedding identity and looked for common points between the identities it contained, which allowed them to meaningfully reconcile the different demands from their overlapping professional identities. Thus, this research introduces the notion of embedding identity as a strategy to make sense of many professional identities. Variability in the embedding identities depicted in this investigation suggests the fluid and contextualized character of professional identity development. How participants saw themselves also influenced how they behaved and interacted with others accordingly. Understanding clinical teacher identity development enriches current perspectives of what it is like to be one of these medical professionals. Faculty development programs ought to consider these perspectives to better support clinical teachers in meeting the overlapping demands in education and patient care.


Using parallel file systems efficiently is a tricky problem due to inter-dependencies among multiple layers of I/O software, including high-level I/O libraries (HDF5, netCDF, etc.), MPI-IO, POSIX, and file systems (GPFS, Lustre, etc.). Profiling tools such as Darshan collect traces to help understand the I/O performance behavior. However, there are significant gaps in analyzing the collected traces and then applying tuning options offered by various layers of I/O software. Seeking to connect the dots between I/O bottleneck detection and tuning, we propose DXT Explorer, an interactive log analysis tool. In this paper, we present a case study using our interactive log analysis tool to identify and apply various I/O optimizations. We report an evaluation of performance improvement achieved for four I/O kernels extracted from science applications.


Determining nucleic acid concentrations in a sample is an important step prior to proceeding with downstream analysis in molecular diagnostics. Given the need for testing DNA amounts and its purity in many samples, including in samples with very small input DNA, there is utility of novel machine learning approaches for accurate and high-throughput DNA quantification. Here, we demonstrated the ability of a neural network to predict DNA amounts coupled to paramagnetic beads. To this end, a custom-made microfluidic chip is applied to detect DNA molecules bound to beads by measuring the impedance peak response (IPR) at multiple frequencies. We leveraged electrical measurements including the frequency and imaginary and real parts of the peak intensity within a microfluidic channel as the input of deep learning models to predict DNA concentration. Specifically, 10 different deep learning architectures are examined. The results of the proposed regression model indicate that an R_Squared of 97% with a slope of 0.68 is achievable. Consequently, machine learning models can be a suitable, fast, and accurate method to measure nucleic acid concentration in a sample. The results presented in this study demonstrate the ability of the proposed neural network to use the information embedded in raw impedance data to predict the amount of DNA concentration.


The present paper analyzed the practices of excluding vocabulary items from the standard language in four major Slavic monolingual dictionaries (Polish, Russian, Serbian, and Slovenian). The analysis has revealed that there exist a range of primary (overt) and secondary (implicit) exclusion labels and that their effect is negotiated in the sociocognitive context of the dictionary, in a communication between the dictionary and its users.


Xiaoning Li Jiangqiao Zhao Huiqing Zhang 5 Jianhui Cai 1Department of Surgery, Hebei Medical University, Shijiazhuang, Hebei 050017, People's Republic of China; 2Department of General Surgery, Hebei General Hospital, Shijiazhuang, Hebei 050051, People's Republic of China; 3Department of General SurgeryII, Baoding First Central Hospital, Baoding, Hebei 071000, People's Republic of China; 4Department of General Surgery, Cangzhou People's Hospital, Cangzhou, Hebei 061000, People's Republic of China; 5Department of Medical, Baoding First Central Hospital, Baoding, Hebei, People's Republic of China Purpose: This study aimed to investigate the regulatory effects and mechanisms of long non-coding RNA (LncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on gastric cancer (GC) cells. Methods: The expression of MALAT1 was detected in GC tissues and two GC cell lines (SGC-7901 and BGC-823). MALAT1 was overexpressed and silenced in GC cells by the transfection of pcDNA-MALAT1 and siRNA-MALAT1, respectively. The proliferation and apoptosis of transfected cells, as well as the tumor volume and weight in mice injected with transfected cells were determined. After identifying the interaction between microRNA-223p (miR-22-3p) and MALAT1/epidermal growth factor receptor 3 (ErbB3), the effects of miR-22-3p/ErbB3 silencing on the proliferation and apoptosis of GC cells were evaluated. Results: MALAT1 was significantly upregulated in GC tissues and cells and negatively associated with the survival of GC patients. Overexpression of MALAT1 significantly promoted the proliferation and inhibited the apoptosis of SGC-7901 cells, while silencing of MALAT1 exerts contrary effects on BGC-823 cells. Silencing of MALAT1 also significantly inhibited the tumor growth in mice. In addition, MALAT1 negatively regulated its target miR-22-3p. Silencing of miR-22-3p reversed the anti-tumor effects of MALAT1 silencing on GC cells. MiR-22-3p negatively regulated its target ErbB3. Silencing of ErbB3 reversed the tumor-promoting effects of miR-22-3p silencing on GC cells. Conclusion: Silencing of MALAT1 inhibited the proliferation and promoted the apoptosis of GC cells through upregulating miR-22-3p and downregulating ErbB3.


The architecture and design of a high-speed quadrature direct digital frequency synthesizer (DDFS) is presented. The architecture is based on a novel multiplier-based angle-rotation algorithm that does not distort the magnitude of the sine and cosine outputs. This algorithm maps well into the DSP slices present in modern FPGAs. The design has a 32-bit frequency control word, 16-bit outputs, and a tuning resolution of 0.23 Hz at 1 GHz. Implemented in a Xilinx Virtex-7 FPGA, the design dissipates 54.9 mW of power, a performance previously attainable only in ASIC designs.


We present an overview of the common types of tubal patency tests, with a focus on hysterosalpingo-foam sonography (HyFoSy). Current evidence suggests that HyFoSy is an accurate alternative to X-ray hysterosalpingography (HSG) for outpatient tubal evaluation in women who are at low risk for tubal disease. It may be superior to saline hysterosalpingo-contrast sonography (HyCoSy) in excluding tubal occlusion. A hyperechogenic medium may enhance contrast visualization and enable clearer delineation of tubal anatomy. This may enhance confidence in the diagnosis of tubal patency, reduce false occlusion results, and improve the diagnostic yield of the test. It would be reasonable to deduce that HyFoSy would have similar performance characteristics as HyCoSy with other positive contrast agents. The available evidence supports the accuracy of HyFoSy compared to other forms of tubal investigation. We suggest a decision-making pathway based on the most current professional recommendations and available evidence. However, in this article, we do not provide a definitive exposition of the methods used for investigating tubal patency. Rather, we explore the contexts in which the various investigations are most and least suitable, and identify their strengths and limitations. Finally, we also discuss challenges encountered when performing tubal contrast sonography in clinical practice, including the problem of false occlusion results.


Turbomachinery flows are characterized by a very high intensity turbulent mean part. As a consequence, laminar flow in boundary layer regions undergoes transition through direct excitation of turbulence. This is the so-called bypass transition. Regions form that are intermittently laminar and turbulent. In particular in accelerating flows, as on the suction side of a turbine blade, this intermittent flow can extend over a very large part of the boundary layer. Classical turbulence modelling based on global time averaging is not valid in intermittent flows. To take correctly account of the intermittency, conditioned averages are necessary. These are averages taken during the fraction of time the flow is turbulent or laminar respectively. Starting from the Navier-Stokes equations, conditioned continuity, momentum and energy equations are derived for the laminar and turbulent parts of an intermittent flow. The turbulence is described by the classical k-e model. The supplementary parameter introduced by the conditioned averaging is the intermittency factor. In the calculations, this factor is prescribed in an algebraic way.Copyright © 1994 by ASME


The multiple isomorphous replacement method of protein crystallography has revealed the structures of several proteins, but the method is limited by the need for many isomorphous crystals. This difficulty could be eased to a large extent by using a molecular fragment as a model for the unknown structure, when only one set of X-ray intensities need be measured. This thesis discusses ways to determine the orientation of such a partial structure, and recommends a new method to determine the location of a properly oriented partial structure in the crystal unit cell. These methods were applied to the proteins human lysozyme, hen lysozyme crystallised at a high temperature, and goat α-lactalbumin, for all of which part of the published structure of hen lysozyme was used as a model. Only the application to human lysozyme was successful, and the failure in the case of the high-temperature hen lysozyme is surprising. An application of these methods to the antibiotic thiostrepton, using an almost complete structure from another crystal form as a model was successful. Having found a partial structure which explains the X-ray data moderately well, it is necessary to complete and refine the model. Several of the theories discussed in this thesis assume Wilson statistics, which are shown to apply to human lysozyme surprisingly well. Three types of completion / refinement technique were applied, a least squares refinement of atomic occupancies, direct methods, and the use of maps with Fourier coefficients with phases derived from the partial structure. The first two methods failed, but the third had partial success. The relationship between "difference maps", Sim weighting, and the α-synthesis is discussed; an extension of Luzzati's treatment of maps with Fourier coefficients F exp(ia c ) shows that of these three Fourier syntheses, the α-synthesis has the best (unknown peak height)/(known peak height) ratio, whereas Sim weighting has the best signal/noise ratio – which, incidentally, never exceeds unity for acentric data – where "noise" is defined in a more realistic way than that adopted by Sim. A corrected and extended version of a previous semi-quantitative account of difference maps is given. The application of various Fourier syntheses to human lysozyme structure factor amplitudes proceeded as a test of methods in parallel with the isomorphous replacement study by other workers; it is recommended that both F obs , and difference maps be calculated, using Sim weighting. Small differences in the main chain conformations of hen and human lysozymes can be determined, missing side chain atoms can often be placed, but rearrangements of the structure as determined by the isomorphous replacement study are not always seen on difference maps. The value of the residual for a randomly wrong structure when a mixture of acentric and centric data is used is shown to be within 0.007 of the value which corresponds to a linear interpolation between the all centric and all acentric limiting cases.


Soil borne pathogens and nematodes are very destructive in vegetable crops and one of the most limiting factors to farmer's income. Soil fumigation has been an essential component of greenhouse crops since the 1960s, but according to the Montreal Protocol (1997), methyl bromide, as an ozone-depleting compound, is banned for plant protection (fumigation applications) in Romania, starting January 2005. Growing vegetables without soil fumigants has remained a challenge, in part because commercially acceptable eggplant cultivars produced through conventional breeding lack resistance to many soil borne plant pathogens. Grafting cultivars with high quality and productivity on rootstocks that are resistant to the soil pests and diseases is a method known for many years, but which was improved and quickly spread in the last years. Therefore, the objective of the research was to evaluate the performance of the eggplant grafting on some rootstocks, in greenhouse conditions. The study was carried out in the experimental greenhouse of the Horting Institute from Bucharest. Data obtained in the combinations scion/rootstock were compared with data recorded from plants not grafted. Disease incidence, disease severity and the attack degree of soilborne disease and pest were determined and calculated in the experimental variants. The grafting process led to significant reduction in the incidence of attack produced by soil borne disease (Fusarium oxysporum f. sp. melongenae, Pyrenochaeta lycopersici) and nematodes (Meloidogyne incognita).


The large centre-of-mass energy available at the Large Hadron Collider (LHC) allows
for the copious production of top quark pairs in association with other final state
particles at high transverse momenta.
Several final state observables that are sensitive to additional radiation in top
anti-top quark final states has been measured by the ATLAS experiment.
The production of top quark pair in association with $W$ and $Z$ bosons or with a
photon have been also measured.
Analyses probing the top pair production with additional QCD radiation include the
multiplicity of jets for various transverse momentum thresholds in the 13 TeV data.
These measurements are compared to modern Monte Carlo generators based on NLO QCD
matrix element or LO multi-leg matrix elements,
and the results are consistent with the standard model predictions within the
uncertainties.


Meatball is a beef-processed food that easily found in the various regions in Indonesia. Price and quality are two factors that are used by consumers in buying this particular food. This study aims to determine the effect of meatball quality and price on consumer purchase decisions. The independent variables in this study are quality and price and the consumer purchase decisions as the dependent variable. Each variable has a few indicators as benchmark. This is a quantitative research. The data were collected using a questionnaire and analyzed using multiple regression. The population in this research was all meatball consumers in the city of Caruban and the sample of 100 respondents drawn using purposive sampling technique. Based on the analysis that has been done, it is known that the quality and price of meatvall influence consumer purchase decisions. The quality of meatball taken from its taste and the bechmark of the price taken from the general prices. The regression results indicate that the quality have a greater influence on the buying decision than the price.


By means of an approach that employs alkali-metal alloys, bulk single-phase (RbxK1–x)3C6O superconductors have been prepared for all x between 0 and 1. For x = 1 it is shown that the maximum superconducting fraction, which approaches 100% in sintered pellets, occurs at a Rb to C60 ratio of 3:1. More importantly, single-phase superconductors are formed at all intermediate values of x, and it is shown that the transition temperature (Tc) increases linearly with x in this series of materials. The formation of a continuous range of solid solutions demonstrates that the rubidium- and potassium-doped C60 superconducting phases must be isostructural, and furthermore, suggests that the linear increase in Tc with x results from a chemical pressure effect.


Infraspecific categories are widely used for Lepidoptera, probably because of the attention from collectors that this order has received, but in other groups of insects their use is more restricted. The terms subspecies, race, form, variety, aberration, phase and caste are all employed by entomologists but with no great consistency. This is unfortunate because the phenomena which they are intended to describe are easily categorized; it should be possible to achieve a more standardized usage.

Since genetic isolation is necessary to permit the divergence of a population to a state on which it may be appropriate to bestow an infraspecific label, factors contributing towards a state of isolation in insect populations are discussed.


We detail in this paper the numerical implementation of the so-called image curvature microscope , an algorithm that computes accurate image curvatures at subpixel resolution, and yields a curvature map conforming with our visual perception. In contrast to standard methods, which would compute the curvature by a finite difference scheme, the curvatures are evaluated directly on the level lines of the bilinearly interpolated image, after their independent smoothing, a step necessary to remove pixelization artifacts. The smoothing step consists in the affine erosion of the level lines through a geometric scheme, and can be applied in parallel to all level lines. The online algorithm allows the user to visualize the image of curvatures at different resolutions, as well as the set of level lines before and after smoothing. Source Code The ANSI C++ implementation reviewed by IPOL is given in the file curv.cpp. The complete source code, code documentation, and online demo are accessible at the IPOL web page of this article 1. The level lines extraction (files levelLine.cpp, lltree.cpp) and level lines smoothing (file gass.cpp) are independent algorithms, out of the scope of this article, and details for their implementation are planned for separate IPOL publications.


Abstract The clay mineralogical composition of 87 topsoil (0–15 cm) samples from inland valleys (IVs) and flood plains (FPs) in seven West African countries, namely Côte d'Ivoire, Ghana, Guinea, Mali, Niger, Nigeria and Sierra Leone, was examined using X-ray diffraction analysis to gain basic information for the development of sustainable lowland agriculture in the region. The results of the present study revealed that the clay fraction (< 2 m) of these samples consisted of 68.4% of 7 Å minerals (low-activity clays such as kaolin minerals), 26.6% of 14 Å minerals (relatively high-activity clays such as smectite and vermiculite) and 5.1% of 10 Å minerals (illite or clay micas) and showed a high variability in the composition. With respect to the soil material classification based on the relative abundance of these three types of minerals, Type 7 (rich in 7 Å minerals) accounted for 42.5% of the total samples, while 39.7% of all the samples were Type 7-10 and 7-14 with a predominance of 7 Å minerals and with negligible amounts of 10 and/or 14 Å minerals, respectively. Type 14-7 accounted for 17.2% of the total samples and was only recorded in Nigeria. The other clay mineral types (i.e. Types 7-10-14, 14, 10, 10-7, 10-14 and 14-10) that were composed mainly of 10 and/or 14 Å minerals were hardly found in the West African lowland soils, whereas Types 14 and 7-10-14 were observed in a vertic soil of Southeast Ghana and in northern Ghana, respectively. In contrast, no significant differences in the clay mineralogical composition were found between the IV and FP soils. Geographical distribution of the soil types showed that the soils in the eastern part of West Africa contained more 14 Å and 10 Å minerals than those in the western part. Although the effect of agro-climatological differences was not conspicuous, soils in the Sahel and Sudan savanna zones showed a higher percentage of 14 Å clay minerals than those in the Guinea savanna and equatorial forest zones. The findings were as follows: (1) the low fertility status of the lowland soils in the region was closely associated with their poor mineralogical characteristics (i.e. predominance of 1:1 type clay minerals and a lower amount of 2:1 type clay minerals), (2) no significant differences in the mean clay mineralogical composition were observed between the IV and FP soils, indicating that the lower fertility of the IV soils mainly resulted from the lower clay content, (3) the clay mineralogy of the West African lowland soils was more strongly influenced by the nature of the parent materials than by the climatic conditions and relief.


This report summarizes the results of studies conducted in FY 1992 to develop methods for the identification and quantification of cyanide species in ferrocyanide tank waste. Currently there are 24 high-level waste storage tanks at the Hanford Site that have been placed on a Ferrocyanide Tank Watchlist because they contain an estimated 1,000 g-moles or greater amount of precipitated ferrocyanide. This amount of ferrocyanide is of concern because the consequences of a potential explosion may exceed those reported previously in safety analyses. The threshold concentration of total cyanide within the tank waste matrix that is expected to be a safety concern is estimated at approximately 1 to 3 wt%. Methods for detection and speciation of ferrocyanide complexes in actual waste are needed to definitively measure and quantitate the amount of ferrocyanides present within actual waste tanks to a lower limit of at least 0.1 wt% in order to bound the safety concern.


While vertebral artery injuries are uncommon, they can have significant morbidity if not identified and treated in a timely fashion. While the majority of vertebral artery injuries are the result of blunt injury and typically have favorable outcomes, a substantial percentage of patients with penetrating injury to the neck may also have vertebral artery injury necessitating angiographic or operative intervention. A 45-year-old male sustained a single stab wound to the apex of the posterior triangle of the neck, below the left mastoid process. At the scene, Emergency Medical Services personnel reported large blood loss and upon arrival, his initial vital signs were consistent with Class II/III hemorrhagic shock. Physical examination revealed a 9 cm longitudinal and deep laceration which began to bleed rapidly and profusely during his inital evaluation. The patient was intubated and rapidly transported to the operating room for exploration of the wound with direct control of the suspected vascular injury via suture ligation and application of vascular clips and to interventional radiology suite for embolization. Operative control was necessary however, immediate post-operative angiography allowed confirmation of collateral cerebral perfusion. The patient had an uneventful recovery and was evaluated in the Trauma Clinic during his 7, 14, 30 and 60-day follow-up.


An integrated pollution assessment index approach was used to assess the application of heavy metal pollution indices in the Ngoua watershed in southwestern (SW) Cameroon. The concentrations of Pb, Cr, Cu, Ni, Zn, Mo, Fe and Al in most of the water samples exceeded the maximum allowable concentration recommended by the World Health Organization (WHO). The Heavy Metal Evaluation Index (HEI) shows strong correlations with the Heavy Metal Pollution Index (HPI), Metal Index (MI) and the degree of contamination (Cd), and gives a better assessment of the pollution levels. Selected samples from the 10 sampling stations were classified as high polluted in Cd, MI and HPI in relation to the respective critical values. These values show comparable results to those of the HEI and indicate that about 88% of the samples with above average values were classified as highly contaminated and the remaining samples (12%) with below average values were classified as moderately contaminated. The Enrichment Factor (EF) analysis and the pollution indices reveal that the water quality is mainly controlled by natural and geogenic processes with major anthropogenic input. The current level of heavy metal distribution in the water of the Ngoua catchment is an environmental and health concern and requires special attention.


Because isoniazid is a selective inducer of CYP2E1 and isoniazid-induced hepatotoxicity is believed to be due to activation of its metabolites by CYP450, this study was undertaken to determine the effect of isoniazid containing regimen on CYP2E1 in TB-patients. The activity of CYP2E1 in 11 newly diagnosed TB-patients (5 F, 6 M) was investigated before (day 0) and during (day 14) treatment for tuberculosis. CYP2E1 activity was measured using the plasma metabolic ratio (MR) of 6-hydroxy-chlorzoxazone to chlorzoxazone, while CYP2E1 quantity in the peripheral lymphocytes was measured using SDS-PAGE. By day 14 of anti-tuberculosis treatment, the activity of CYP2E1 was inhibited by 72% in 8 patients, but increased in 3 patients. The MR for the 8 patients was reduced from (Median & Range) 2.78 (1.1-21.5) on day 0, to 0.75 (0.4-1.22) on day 14, (P = 0.0006). Renal function was normal before and during the investigation. The detection of CYP2E1 by in peripheral lymphocytes was so variable that it could not be correlated with enzyme activity. Nevertheless, its detection in peripheral lymphocytes where normally is not resident indicates that CYP2E1 was induced by isoniazid. These results indicate that during treatment for tuberculosis with isoniazid containing regimen, CYP2E1 is induced but its activity is inhibited by isoniazid.


Petri Net, a widely studied mathematical formalism, is a graphical notation for modeling systems. Petri Nets provide the foundation for modeling concurrency, communication, synchronization, and resource sharing constraints that are inherent to many systems. However, Petri Nets do not scale well when it comes to modeling and simulating large systems. Colored Petri Nets (CPNs) extend Petri Nets with a high level programming language, making them more suitable for modeling large systems. The CPN language allows the creation of models as a set of modules in a hierarchical manner and permits both timed and untimed models. Untimed models are used to validate the logical correctness of a system, whereas timed models are used to evaluate performance. This tutorial introduces the reader to the vocabulary and constructs of both Petri Nets and CPNs and illustrates the use of CPN Tools in creating and simulating models by means of familiar simple examples.


Rhinitis or asthma or both occur in some people because a specific reaginic antibody (IgE) develops after exposure to a particular allergen, for example house dust or grass pollen, and becomes attached to the surface of mast cells in nasal and bronchial tissue. Subsequent exposure of these tissue sites to the allergen and consequent interaction of allergen and reaginic antibody on the surface of mast cells results in their disruption with release of various substances which act on blood vessels and plain muscle and so cause the symptoms of asthma or rhinitis. Injections of successively increasing concentrations of the allergen (hyposensitisation) are widely used to treat these conditions. Where such treatment is effective it is suggested that the injections increase the plasma concentrations of 'blocking' antibody (IgG) specific for this allergen, so mopping up allergen that enters the body later and 'blocking' the union of allergen and IgE on the surface of mast cells, thus preventing the damaging reactions.


While it has long been possible to study the process of recombination in yeast and other single‐celled organisms, it has been difficult to distinguish between pathways of meiotic and mitotic recombination in multicellular eukaryotes. The experimental system described here bridges the historically separated fields of Genetic Recombination and DNA Repair in Drosophila. It is now feasible to study the repair of unique double‐strand breaks induced in the Drosophila genome by the excision of a P‐transposable element or by cleavage at an introduced endonuclease recognition sequence. This repair can be studied in both somatic cells and mitotically dividing germ cells. The repair of these breaks occurs mainly by copying sequence from a template located anywhere in the karyoplasm, and occurs in both male and female flies. This system, which was the first of its kind in metazoan organisms, is now being used for gene targeting in Drosophila. This review summarizes results that provide new insights into the process of gap repair in Drosophila and outline some recent experiments that demonstrate the power of the gene targeting technique. BioEssays 20:317‐327, 1998.© 1998 John Wiley & Sons, Inc.


Among the species of the genus Passiflora, P. foetida L. presents highest genetic variability and also great medicinal importance. This species is used in the treatment of diseases such as asthma, jaundice, and in the form of poultices for erysipelas and skin diseases with inflammation. Therefore, studies are needed to preserve them. Its seeds present dormancy and often take several months to germinate. The tissue culture is a alternative form to propagate species. The objective was to establish and micropropagation P. foetida L., and create a germplasm bank. Seeds were scarified, disinfected, and inoculated on MS medium (½) without regulators for 66 days. Hypocotyls explants obtained of seedlings in vitro germinated were transferred and placed in the same medium supplemented with BAP (1,0 mg L-1). In the establishment phase of 45% of the explants sprouted and formed axillary buds. 88,9% of hypocotyl explants induced shoots and 11,1% produced callus. Seedling measuring 1,82 cm length and rooted were acclimatized.


This paper presents a new method for person-specific face shape estimation under varying head pose of a previously unseen person from a single image. We describe a featureless approach based on a deformable 3D model and a learned face subspace. The proposed approach is based on maximizing a likelihood measure associated with a learned face subspace, which is carried out by a stochastic and genetic optimizer. We conducted the experiments on a subset of Honda Video Database showing the feasibility and robustness of the proposed approach. For this reason, our approach could lend itself nicely to complex frameworks involving 3D face tracking and face gesture recognition in monocular videos.


A numerically based method is used for deriving an expression for the stress cone profile of termiated high voltage cables. The application to a compact 138 kV XLPEI cable with XLPE molded termination is demonstrated The profile expression is in terms of the cable insulation radius and the specified maximum longitudinal electric stress at the profile.


We describe a time-integrating acousto-optic correlator that allows several channels to be multiplexed optically by means of a coherence-multiplexed superluminescent laser diode. Parallel channels are generated by birefringent electro-optic modulators set in cascade to induce optical path differences greater than the coherence length of the source. The system can be combined with most of the other previously reported multichannel techniques used in acousto-optic processors.


Skeletal muscle relaxants (SMR) are commonly used drugs prescribed for the treatment of muscle spasm and discomfort. Although many have been in use for decades, physicians may be unaware of the accumulating evidence of their risks, benefits, safety and side effects. This review examines the efficacy, side effects, and safety of three commonly prescribed SMRs: metaxalone, cyclobenzaprine, and carisoprodol. All three appear to have equal efficacy, but their side effects vary considerably. Metaxalone has the fewest reports of side effects, and no reports of major safety issues. Cyclobenzaprine, closely related to the tricyclic antidepressants, causes the expected lethargy and anticholinergic side effects, and may have some toxicity in overdose and in combination with other substances. Carisoprodol raises the greatest concern. Reports in the literature suggest a significant potential for physical and psychological dependence perhaps suggesting a potential for misuse. It also has, perhaps, the greatest toxicity. A secondary goal of this review is to stimulate more discourse about these commonly used, but poorly understood compounds.


Influence of cross-section magnetic field on a positive columb of the gas charge is consedered. Analitical expressions for concentration of the charged particles are designed and analysed depending Cross - section coordinate. It is shown, that at growth of magnetic field from zero value, baundery concentration increases from zero and reaches the maximal value. At enough strong magnetic field, dependent on parameters of plasma, boundery concentration again to aspire to zero.


Risperidone is one of the most widely used atypical antipsychotic drugs and is approved for the treatment of mental disorders (eg. schizophrenia, autism) in children and adolescents. The present study investigated the repeated treatment effect of risperidone and associated neurotropic mechanism in the phencyclidine (PCP)-induced hyperlocomotion model in adolescent rats. We examined whether repeated risperidone treatment would cause a sensitized inhibition of PCP-induced hyperlocomotion in adolescent rats, and whether such a sensitization effect was mediated by risperidone-induced alterations in Brain-Derived Neurotrophic Factor (BDNF), an important biomarker which plays a role in neuropathology of schizophrenia and action of antipsychotic medications. Male adolescent Sprague-Dawley rats (postnatal days [P] 44-48) were first treated with risperidone (0.5 or 1.0 mg/kg, sc) or vehicle and tested in the PCP (3.2 mg/kg, sc)-induced hyperlocomotion model for 5 consecutive days. Three days later, all rats were then challenged with risperidone (0.5 mg/kg) and PCP on ~P 51 to assess the potential sensitization effect. They were then sacrificed 1 day later and BDNF levels in the prefrontal cortex (PFC), striatum and hippocampus were examined using Western blotting. Behaviorally, repeated risperidone treatment progressively increased its inhibition of PCP-induced hyperlocomotion across the 5 test days. In the subsequent challenge test, rats previously treated with risperidone 1.0 mg/kg showed a stronger inhibition of the PCP-induced hyperlocomotion than those previously treated with vehicle, indicating a robust risperidone sensitization. However, no such group differences in the BDNF and its precursor proteins in any of the three brain regions were found. Therefore, although repeated adolescent risperidone administration induced a sensitization effect in the PCP-induced hyperlocomotion model in a dose-dependent fashion, whether BDNF is critically involved in this effect is still unsettled. Future work that directly manipulates BDNF systems is needed to further investigate this issue.


This study traces the development of Native Studies at Canadian universities from 8its ivory tower origins through its gradual descent to the grass roots by examining four programs which emerged in four different decades in four different provinces. The unique characteristics of the programs and the circumstances which led to these differences, namely, the times in which each program was established, the location of the program, the program's structure, and the level of involvement of the First Nations in each university are explored. The study demonstrates that since Native Studies first burst upon the academic scene in the late sixties, the programs have steadily increased their responsiveness to First Nations' needs by expanding the curriculum, increasing the participation of Native students and instructors, reaching out to the communities, and involving First Nations people as cultural consultants and throughout the universities' governing bodies. Through a series of interviews with those involved in the programs and an examination of university records, the differences in the origins of the four programs and the unique ways in which each program has approached Native Studies are revealed.


Benign paroxysmal positional vertigo (BPPV) frequently occurs in females over 50 years old, suggesting that a postmenopausal decrease in estrogen secretion might be involved in its onset. An estrogen deficiency is generally known to cause osteoporosis through a reduction in bone mass. This study was designed to investigate a clinical association between idiopathic BPPV and osteoporosis.


Antibody-functionalized nanoparticles (NPs) have shown numerous benefits in drug delivery and biosensing, improving the specificity of cell targeting and analyte detection, respectively. However, one of the main challenges is the lack of control over antibody orientation on the NP surface. Popular and easy conjugation strategies, such as carbodiimide-based conjugations, lead to a random orientation of antibodies on the NPs, compromising ligand functionality and contributing to undesired biological effects and reduced target recognition. While new methods for more controlled NP functionalization have been proposed, there is a lack of techniques that can elucidate the orientation of the antibodies at the single-particle level to determine the conjugation outcome and, therefore, the NPs' potential in selective targeting. Here, spectrally-resolved direct stochastic optical reconstruction microscopy (SR-dSTORM), an optical super-resolution technique, is introduced to quantify the relationship between total and functional NP conjugated cetuximab antibodies at the single-particle level. An evident single-particle heterogeneity in total and functional cetuximab is observed, leading to particles with different functional : total ratios. Additionally, the results indicate that the functional : total ratio of cetuximab highly depends on the conjugated cetuximab concentration. Overall, SR-dSTORM represents a direct approach for the NP structure–functionality relationship quantification, providing a platform to improve antibody-conjugated NPs characterization and facilitating their rational design.


Manufacturing enterprises are increasingly more aware of the importance of establishing collaborative relationships with their network partners, due to the advantages associated to collaboration. Nevertheless, the participation in a collaborative network (CN) comes with associated challenges, namely the need to reduce the potential for conflicts among partners. A CN consists of heterogeneous partners, each one defining its own objectives and activating its own strategies. In this context, the ability to quickly identify partners with aligned strategies is crucial for smooth operation of the CN. The main aim of this paper is to address the partners' selection problem in the context of Virtual organizations Breeding Environments (VBE) that facilitate and enable the creation of Virtual Organisations (VO), as one type of CN. In a first stage, the sets of enterprises, characterised by having the required competencies to create the VO, are identified among different potential candidates within the VBE. In a second stage, the strategies alignment approach, based on the system dynamics simulation method, is used for the partners' selection process, identifying the best set of enterprises. In this paper, the final stage of partners' selection process is addressed by obtaining the degree of alignment of the business strategies formulated by each set of enterprises. In the light of this, a system dynamics-simulation model, in AnyLogic, is presented to obtain the set of enterprises that have higher levels of alignment in its strategies. The proposed system dynamics-simulation model is applied to a case in the building industry, to deal with the partners' selection problem in a VBE with the aim of forming a stable and sustainable VO.


The paper discloses the question of ambivalent character of the metaphor as means of expression of the meaning. The metaphor appears as effective phenomenon in cognitive process. At the same time, in particular philosophical texts the metaphor can reduce the subject of the research and bring self-contradictory meanings. The author's position consists in the idea that in general the metaphor is not effective means for the practical research, however, the metaphorical argumentation reveals the dual character of social or historical phenomena. The author demonstrates the functioning of the social metaphors with examples of the works of T. Hobbes, J. Locke, K. Marx and shows that they can be reconsidered conceptually in the light of context of the use. Depending on the such context, self-contradiction appears, ambivalence of the metaphorical potential and the meaning of the research phenomenon can appear ambiguous. Using the methods of the analysis and comparison, the author aimed at re-analyzing the metaphor as means of the search and reflection of the sense; reflecting its ambivalent character in cases when it is used in the social or epistemological researches; revealing the dual connotation of the metaphorical argumentation in particular philosophical works. Generalized results of the paper can be shown by the following statements: 1) The metaphorical meaning of concepts in social, historical, epistemological practice partly replaces the direct meaning and forms further human culture in a trail from deviation to norm. 2) The concepts "Leviathan" (T. Hobbes), "voice of reason" (J. Locke), "capital" (K. Marx) in metaphorical interpretation form ambivalent historical narratives of criteria of the justice, the truth, the social law and in as such form further human culture. 3) The inner potential of the researches connected with the variety of metaphorical uses is especially important to the sphere of socio-philosophical and socio-political searches.


Background: Intense efforts to improve current molecular therapy in pancreatic ductal adenocarcinoma (PDAC) have focused on suppression of the MAPK/ERK1/2 pathway. Inhibitors of MEK1/2, downstream target of the frequently mutated RAS oncogene, are currently in development. Recently, results of a phase II clinical trial revealed that selumetinib, a second-generation MEK1/2 inhibitor, has not yielded its promising preclinical efficacy in PDAC patients. A novel Extracellular Signal Regulated Kinase 1/2 (ERK1/2) inhibitor, VTX-11e, has been recently developed as a potent and selective inhibitor of ERK1/2. In this study, we evaluated the effects of VTX-11e on cell growth and apoptosis in pancreatic cancer cell lines and compared VTX-11e to selumetinib. Methods: Fifty percent Growth Inhibition (GI50) and Lethal Dose (LD) were determined at 72 hours in 65 PDAC cell lines with increasing concentrations of VTX-11e or selumetinib. Apoptosis was quantified by Annexin V/PI following VTX-11e or selumetinib treatment at increasing concentrations at 24 and 72 hours and 7 days. Elk1 phosphorylation levels were determined by Western Blotting as a well-established readout for downstream MAPK pathway output. Results: More than a third of VTX-11e-treated PDAC lines showed GI50 concentrations of ≤2μM. LD drug response curves of cell lines treated with VTX-11e showed cell death induction at lower concentrations than selumetinib in close to half the cell lines tested. This finding was confirmed by assessment of apoptosis by the AnnexinV/PI assay. We demonstrated that VTX-11e induced significant increased apoptosis in a subset of the PDAC lines compared to selumetinib, leading to as much as 50% apoptotic cells. Furthermore, VTX-11e and selumetinib suppressed phosphorylation of downstream target Elk1 equally. Conclusion: Our results show that the novel ERK1/2 inhibitor VTX-11e leads to a significant increase in apoptosis as compared to the MEK1/2 inhibitor selumetinib in a subset of pancreatic cancer cell lines. This finding suggests that targeting ERK1/2 directly may be a more effective therapeutic strategy than targeting upstream MEK1/2 in some PDAC. Current studies are ongoing to determine the differential mechanism of action between VTX-11e and selumetinib. Citation Format: Anne M. Miermont, Holger Pflicke, Hannah Guan, Harshini Chinnasamy, Craig Thomas, Udo Rudloff. Direct inhibition of ERK1/2 by VTX-11e leads to increased induction of apoptosis in a subset of pancreatic cancer cell lines as compared to MEK1/2 inhibition by selumetinib (AZD6244). [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 5538. doi:10.1158/1538-7445.AM2013-5538


Role-based access policies model the users domain by means of complex structures where roles, which represent jobs or responsibilities assumed by users, are specialized into more concrete subroles which inherit properties and authorizations from their parents. Such an approach can be applied within the context of educational applications, where different roles are easily identified each of which has different views of the same information items and different capabilities to modify them. Moreover, even though this approach, has only been oriented towards modeling security requirements, it can be extended to support personalized access to the information. In this paper, we describe how to combine the basic principles of RBAC policies and adaptation with a view of providing personalized access to the different types of users of a web-based course. Moreover, we also present Courba, a platform to generate personalized web-based courses using XML to support the definition of access policies.


Enterprise data integration is the process of combining data from multiple sources to fulfil business and market needs. Traditional approaches such as shared databases and messaging-oriented systems fall short of new challenges to keep pace with the evolution of big data in changing markets. Such challenges can be observed at two levels. First, during integration design we need to establish a concise, visual and loosely-coupled mapping to support data integration without disturbing internal business process and applications. Second, at the execution level we need to support efficient bidirectional transformations and synchronisations to respond to evolving requirements in a cost-effective manner. Graph databases such as neo4j are designed to handle and integrate big data from heterogeneous sources using efficient navigation based query languages such as Gremlin. For flexibility and performance, they do not ensure data quality through schemata but leave it to the application level. They are built on top of a rich data model that can be utilised to realise the interconnectedness of real-world data domains. On the other hand, model-driven design and implementation techniques have been widely adopted to build systems at a high level of abstraction. They exploit visual relational models such as the Unified Modelling Language (UML) to describe systems at various stages of development and allow to automatically generate application logic. In this thesis, we present a model-driven approach to bidirectional transformations and synchronisations between relational sources in neo4j. We describe data sharing between relational sources using declarative Triple Graph Grammars (TGGs), then compile them into query and update operations in Gremlin to execute controlled transformations and synchronisations in neo4j using a Model-To-Text (M2T) transformation approach. To ensure the validity and the efficiency of our approach, we evaluate the correctness and the performance of generated Gremlin queries using well-known bidirectional transformations testing suites. The results show that our approach is valid and efficient to support enterprise data sharing and synchronisations. The approach combines the data quality of schema-based solutions while utilising the performance of Gremlin queries on neo4j to perform loosely coupled incremental data transformations for data driven applications.


A superlattice structure of planar metamaterial is fabricated, where the orientation of double-split ring resonators is altered in a periodic way. A time-domain terahertz transmission spectrum shows an enhanced Q-factor resonance appears when a closed mode is selectively excited by angular tuning of polarization direction. The polarization-angle selective resonance in metamaterial superlattice has a potential application in the selective field enhancement for spectroscopy.


We derive the efficiencies of two new tests for exponentiality which are based on a recent characterization that uses the idea of a random shift. The finite-sample performance of the newly proposed tests is evaluated and compared to other existing tests by means of Monte Carlo simulations. It is found that the new tests perform favourably when compared to the other tests. Overall the best performing tests seem to be our new Kolmogorov-Smirnov type test, the score function based test by Cox and Oakes, and the Kolmogorov-Smirnov type test based on the mean residual life. The tests are also applied to a real-world data set with i.i.d. data as well as to simulated data from a Cox-proportional hazards model, where we test whether the so-called Cox–Snell residuals follow a standard exponential distribution.


This study derives from and extends the discussions of a US DOE sponsored workshop held on 30 and 31 May, 2000 in Boulder, CO concerning issues and uncertainties related to long-term eddy covariance measurements of carbon and energy exchanges. The workshop was organized in response to concerns raised at the 1999 annual AmeriFlux meeting about the lack of uniformity among sites when making spectral corrections to eddy covariance flux estimates and when correcting the eddy covariance CO2 fluxes for lack of energy balance closure. Ultimately, this lack of uniformity makes cross-site comparisons and global synthesis difficult and uncertain. The workshop had two primary goals: first, to highlight issues involved in the accuracy of long-term eddy covariance flux records; and second, to identify research areas and actions of high priority for addressing these issues. Topics covered at the workshop include different methods for making spectral corrections, the influence of 3D effects such as drainage and advection, underestimation of eddy covariance fluxes due to inability to measure low frequency contributions, coordinate systems, and nighttime flux measurements. In addition, this study also covers some new and potentially important issues, not raised at the workshop, involving density terms to trace gas eddy covariance fluxes (Webb et al., 1980) . Wherever possible, this paper synthesizes these discussions and make recommendations concerning methodologies and research priorities. Published by Elsevier Science B.V.


We demonstrate experimentally that chirping of broadband 15-fs pulses has drastic effects on the differential transmission (DT) response of bulk semiconductors for excitation well above the bandgap. In particular, the rise and the initial fast decay of the spectrally integrated (SI) DT response and the shape of DT spectra are modified by chirp in an unexpected way. These new results have an impact on both fundamental studies and ultrafast switching applications as, for example, mode locking of solid-state lasers. Experiments were performed on a 200-nm thick Al/sub 0.06/Ga/sub 0.94/As sample at 300 K.


Herpes simplex virus type 1 (HSV-1) has great potential to be applied as a viral tool for gene delivery or oncolysis. The broad infection tropism of HSV-1 makes it a suitable tool for targeting many different cell types, and its 150 kb double-stranded DNA genome provides great capacity for exogenous genes. Moreover, the features of neuron infection and neuron-to-neuron spread also offer special value to neuroscience. HSV-1 strain H129, with its predominant anterograde transneuronal transmission, represents one of the most promising anterograde neuronal circuit tracers to map output neuronal pathways. Decades of development have greatly expanded the H129-derived anterograde tracing toolbox, including polysynaptic and monosynaptic tracers with various fluorescent protein labeling. These tracers have been applied to neuroanatomical studies, and have contributed to revealing multiple important neuronal circuits. However, current H129-derived tracers retain intrinsic drawbacks that limit their broad application, such as yet-to-be improved labeling intensity, potential nonspecific retrograde labeling, and high toxicity. The biological complexity of HSV-1 and its insufficiently characterized virological properties have caused difficulties in its improvement and optimization as a viral tool. In this review, we focus on the current H129-derived viral tracers and highlight strategies in which future technological development can advance its use as a tool.


The human neuro-musculoskeletal system constantly deploys passive (e.g., posture adjustment) and active (e.g., muscle co-contraction) control strategies to regulate upper limb impedance and stability while interacting with the outside world. Upper limb impedance has been assessed through in vivo experiments and model-based simulations. The experiments are practically limited to small samples of able-bodied subjects and few limb postures, and model-based approaches have mostly used simplified upper limb models. Our objective was to develop and validate a computational approach to estimate upper limb impedance parameters - stiffness, viscosity, and inertia - at the endpoint (i.e., hand) using a neuromusculoskeletal model with realistic geometry. We added a planar manipulandum to an existing upper limb model implemented in OpenSim (version 3.3) and used contact modeling to attach the manipulandum's handle to the musculoskeletal model's hand. The hand was placed at several locations lateral to the shoulder joint along anterior/posterior and medial/lateral axes. At each location, during forward dynamics simulations, the manipulandum applied small perturbations to the hand in eight different directions. The spatial variation of the computed, model-based impedance parameters was similar to that of experimentally measured impedance parameters. However, the overall size of the stiffness and viscosity components was larger in the model than from experiments.Clinical Relevance— Computational modeling and simulations can estimate upper limb impedance properties to complement and overcome the limitations of experiments, especially for clinical populations. The computational approach could ultimately inform new interventions and devices to restore limb stability in people with shoulder disabilities.


A team of three researchers published Two Thousand Sentences of Tokunoshima Dialect with a DVD whose main content includes KWIC (Key Word In Context) reference data in Tokunoshima dialect. KWIC is a very powerful tool for analyzing the dialect. Moreover, the raw data from which the KWIC was made and the programs for processing the data are also included in the DVD. Thus, how the final result
was obtained is made clear in this article.


Between 1808 and 1862 the British Navy liberated an estimated 99,000 Africans from the transatlantic slave trade and settled them in and around Freetown, Sierra Leone. Many of these Liberated Africans received a missionary education, allowing to them to record accounts of their enslavement. The narratives of Liberated Africans Samuel Crowther and Joseph Wright rank among the best-known narratives of Africans who endured enslavement in Africa. Equally detailed but heretofore unpublished is the narrative of James Will, born Kealoo in the western extremities of Yorubaland in the present-day Republic of Benin. Captured in war as a child around 1830, Kealoo was sold into transatlantic slavery by the notorious Brazilian slave dealer Francisco Felix de Souza, passing through the port of Ouidah. This paper traces Kealoo's voyage from enslavement to emancipation, and his rise from apprentice to affluent trader and Methodist preacher in colonial Freetown. As a victim of the Yoruba wars, Kealoo's narrative elucidates the personal impact of processes that dispersed an unprecedented number of Yoruba speakers throughout the Atlantic in the nineteenth century.


The reactions of a series of strained bicyclic and tricyclic one-carbon bridged lactams with organometallic reagents have been investigated. These amides permit isolation of a number of remarkably stable hemiaminals upon nucleophilic addition to the twisted amide bonds present in the lactam precursors. The factors that affect the stability of the resulting bridged hemiaminals are presented. In some cases, the hemiaminals were found to collapse to the open-form amino ketones in a manner expected for traditional carboxylic acid derivatives. Transannular N...C=O interactions were also observed in some nine-membered amino ketones. Additionally, tricyclic bridged lactams were found to react with some nucleophiles that typically react with ketones but not with planar amides. The effect of geometry on the reactivity of amide bonds and the amide bond distortion range that marks the boundary of amide-like and ketone-like carbonyl reactivity of lactams are also discussed.


Osteoarthritis (OA) is a common and often disabling condition affecting older adults. Treatment using anti-inflammatory drugs (NSAIDs) often contributes to morbidity ( 1 ). It is a common reason for people seeking help from primary care ( 2 ). However, unfortunately management approaches often reflect the ageist view that OA is an inevitable consequence of ageing.


Hydrogen sulfide (H2S) is an endogenously produced signaling molecule that can be cytoprotective, especially in conditions of ischemia/reperfusion injury. However, exposure to exogenous H2S can be toxic, perhaps due to unregulated activation of endogenous H2S signaling pathways. We use the nematode C. elegans to define mechanisms that mediate the physiological effects of H2S in animals. We have previously shown that in C. elegans the hypoxia inducible factor (hif-1) coordinates the initial transcriptional response to H2S and is essential to survive exposure to low concentrations of H2S. In this study, we performed a forward genetic screen to identify mutations that suppress the lethality of hif-1 mutant animals in H2S. The mutations we recovered do not suppress embryonic lethality or reproductive arrest of hif-1 mutant animals in hypoxia, nor can they improve viability of hif-1 mutant animals exposed to hydrogen cyanide, indicating that these are specific for H2S. We found that the hif-1 suppressor mutations activate the skn-1/Nrf2 transcription factor. Activation of SKN-1 by hif-1 suppressor mutations increased the expression of a subset of H2S-responsive genes, consistent with our previous finding that skn-1 plays a role in the transcriptional response to H2S. Using transgenic rescue, we show a single gene, rhy-1, alone is sufficient to protect hif-1 mutant animals in H2S. Our data indicate that RHY-1 acts in concert with CYSL-1, an orthologue of human cystathionine β-synthase, to promote survival in H2S. The rhy-1 gene encodes a predicated O-acyltransferase enzyme that has previously been shown to negatively regulate HIF-1 activity. Our studies reveal a novel function of RHY-1, which is independent of hif-1, that protects against toxic effects of H2S.


—With the rise in the adaptation of edge computing frameworks for application deployment, one should decide where to place the enormous amounts of data generated at the edge to provide satisfactory services. Some edge applications like augmented reality games have co-located end-users which provide an opportunity to use location and network proximity as measures to identify the best storage nodes. However, given the resource constraints of heterogeneous edge server nodes, data placement algorithms should consider the storage capacity, fan-in and fan- out limits to ensure low-latency services. In this paper, we discuss three data placement strategies (distance, latency, and spatial) that consider different factors like location, network latency, storage capacity, and fan in/out distributions with dynamic replication of read-only data. Based on our simulation and emulation experiments, distance and latency-based strategies are best suited for sparse edge environments and the spatial for dense edge environments.


Many vertebrates have an ocular skeleton composed of cartilage and/or bone situated within the sclera of the eye. In this study we investigated whether modern and fossil sharks have an ocular skeleton, and whether it is conserved in morphology. We describe the scleral skeletal elements of three species of modern sharks and compare them to those found in fossil sharks from the Cleveland Shale (360 Mya). We also compare the elements to contemporaneous arthrodires from the same deposit. Surprisingly, the morphology of the skeletal support of the eye was found to differ significantly between modern and fossil sharks. All three modern shark species examined (spiny dogfish shark Squalus acanthias, porbeagle shark Lamna nasus and blue shark Prionace glauca) have a continuous skeletal element that encapsulates much of the eyeball; however, the tissue composition is different in each species. Histological and morphological examination revealed scleral cartilage with distinct tesserae in parts of the sclera of the porbeagle and blue shark, and more diffuse calcification in the dogfish. Strengthening of the scleral cartilage by means of tesserae has not been reported previously in the shark eye. In striking contrast, the ocular skeleton of fossil sharks comprises a series of individual elements that are arranged in a ring, similar to the arrangement in modern and fossil reptiles. Fossil arthrodires also have a multi‐unit sclerotic ring but these are composed of fewer elements than in fossil sharks. The morphology of these elements has implications for the behaviour and visual capabilities of sharks that lived during the Devonian Period. This is the first time that such a dramatic variation in the morphology of scleral skeletal elements has been observed in a single lineage (Chondrichthyes), making this lineage important for broadening our understanding of the evolution of these elements within jawed vertebrates.


Electrical distribution is one of the most important parameters in industrial processes. Therefore, good power quality is needed as a supply to industrial machines. The use of industrial machines has an impact on the emergence of harmonics. As a result of the large Harmonics, the quality of power is getting worse, affecting productivity in the industry. Therefore, samples were taken using a Power Quality Analyzer on an 800 kVA transformer on the secondary side of the transformer to maximise the supply of electricity to consumers. Then obtained THDi Phase L1 of 23.1%, phase L2 of 24.7% and phase L3 of 21% and IHDi on the 5th order in phase L1 18.3%, phase L2 20.7% and phase L3 16.6% regarding (IEEE Std 3002.8-2018) and (SPLN D5.004-1:2012) the IHDi value should not be more than 7%. Then simulated using MATLAB/Simulink by designing the Second Order High Pass Filter and C-Type Filter. The results obtained by combining the two filters gained THDi results in the L1 phase at 2.53%, the L2 phase at 2.69% and the L3 phase at 2.22% and the IHDi at the 5th order of the L1 phase at 1.48%, the L2 phase 1.62% and L3 phase 1.33%.


This paper covers the proposed solution for security of computer network in the Ministry of Defence and the Serbian Armed Forces using virtual honeynets. The security is covered from the aspect of the architecture of computer networks with Internet access. The proposed usage of virtual honeynets for protection takes into account the accomplishments of science in this field as well as security methods and techniques, users' needs and opportunities along with the computer network components of the MoD and the SAF that can be targets for attack.


MXene, a new class of 2D materials, has gained significant attention owing to its attractive electrical conductivity, tunable work function, and metallic nature for wide range of applications. Herein, delaminated few layered Ti3C2Tx MXene contacted Si solar cells with a maximum power conversion efficiency (PCE) of ≈11.5% under AM1.5G illumination are demonstrated. The formation of an Ohmic junction of the metallic MXene to n+‐Si surface efficiently extracts the photogenerated electrons from n+np+‐Si, decreases the contact resistance, and suppresses the charge carrier recombination, giving rise to excellent open‐circuit voltage and short‐circuit current density. The rapid thermal annealing process further improves the electrical contact between Ti3C2Tx MXene and n+‐Si surface by reducing sheet resistance, increasing electrical conductivity, and decreasing cell series resistance, thus leading to a remarkable improvement in fill factor and overall PCE. The work demonstrated here can be extended to other MXene compositions as potential electrodes for developing highly performing solar cells.


The aim of this study was to investigate the effects of aerobic activity on Serum IgG concentration. Consequently, 10 male physical education students with age ranging from 21 to 24 years old and mean body mass index 22.22 kg m2 volunteered to participate in this study. Aerobic activity was performed on bicycle ergometer for 30 minutes at intensity of 70 to 75 percent of maximum heart rate. Blood samples were obtained from subjects before and after aerobic activity. Changes in serum IgG concentration in pre-test and post-test were analyzed by dependent t-test using spss software. The results showed that aerobic activity not significantly effect on Serum IgG concentration (p=0.357). This study concludes that sub maximal aerobic activity does not affect on serum IgG concentration and there is no concern for athletes and coaches that sub maximal aerobic activity can impair immune function.


Java is very densely populated since it is inhabited by more than 60% of the total population of Indonesia. Based on data from the Ministry of Forestry, forest loss between 2000-2005 in Java was about 800,000 hectares. Regardless of the debate on whether the different methodologies of forest inventory applied in 2005 have resulted in an underestimation of the figure of forest loss or not, the decrease of forest cover in Java is obvious and needs immediate response. Spatial modeling of the deforestation will assist the policy makers in understanding this process and in taking it into consideration, when decisions are made on the issue. Moreover, the results can be used as data input to solve environmental problems resulting from deforestation. The authors of this chapter modeled the deforestation in Java by using logistic regression. Percentage of deforested area was considered as the response variable, whilst biophysical and socioeconomic factors, that explain the current spatial pattern in deforestation, were assigned as explanatory variables. Furthermore, the authors predicted the future deforestation process, and then, for the case of Java, it was validated with the actual deforestation derived from MODIS satellite imageries from 2000 to 2008. Results of the study showed that the impacts of population density, road density, and slope are significant. Population density and road density have negative impacts on deforestation, while slope has positive impact. Deforestation on Java Island tends to occur in remote areas with limited access, low density population and relatively steep slopes. Implication of the model is that the government should pay more attention to remote rural areas and develop good access to accelerate and create alternative non agricultural jobs in order to reduce pressure on the forest.


The appropriate duration of therapy is often open to question. Extended antimicrobial therapy is associated with selection of resistant organisms, adverse events, expense and poor patient compliance. Evidence suggests that a short duration of treatment is as effective as a longer course of treatment for certain common community-acquired infections, such as acute otitis media, acute bacterial sinusitis, infectious exacerbations of chronic bronchitis, community-acquired pneumonia,and acute pyelonephritis.


The objects of this study are eight X-Men: First Classcomic books, volume 1 published from September 2006 until April 2007 andX-Men: First Classmovie made in 2011.Texts in the forms of dialogues and visual images taken both from the comic books and the movie are the data which then are analysed qualitatively. Applying intersemiotic translation promoted by Zecca, this study is trying to uncover how social and economic factors influence translation process and whether there are any continuity and changes along the process.
            The study focuses on the social and economic aspects involved in the process of transforming X-Men: First Class comic books as the source text, into the movie version as the targeted texts. Some adaptation and changes occurred as the consequence; plot and story lines are twisted, characters involved are replaced for the purpose of meeting the expectation of the targeted market of the movie. Supported by those who were involved in the process and the social issues echoing at the time when the process is happening, the social issues depicted in the texts are also sifted.


The traditional philosophy of science approach to prediction leaves little room for appreciating the value and potential of imprecise predictions. At best, they are considered a stepping stone to more precise predictions, while at worst they are viewed as detracting from the scientific quality of a discipline. The aim of this paper is to show that imprecise predictions are undervalued in philosophy of science. I review the conceptions of imprecise predictions, and the main criticisms levelled against them: (i) that they cannot aid in model selection and improvement and (ii) that they cannot support effective interventions in practical decision making. I will argue against both criticisms, showing that imprecise predictions have a circumscribed but important and legitimate place in the study of complex heterogeneous systems. The argument is illustrated and supported by an example from conservation biology, where imprecise models were instrumental in saving the kōkako from extinction.


Spent mushroom substrate (SMS) is a noxious byproduct of the mushroom industry. The aim of this work was to convert SMS into organic-mineral micronutrient (Zn(II), Mn(II), and Cu(II)) fertilizer via biosorption and examine the effect of its application in field tests on maize compared to commercial reference micronutrient fertilizer. Crop yield and crop quality were assessed, and multielemental analysis of grains was conducted for the evaluation of the fertilization effect on maize grains and to assess bioavailability of nutrients from fertilizers. Grain yield for maize treated with micronutrients delivered with SMS was noticeably higher (11.5%) than the untreated group and the NPK (nitrogen, phosphorus, potassium) fertilizer treated only group (2.8%). Bioavailability (TF) of micronutrients from SMS were comparable with reference micronutrient fertilizer (7% Zn, 4% Mn, and 2.3% Cu). The new product has the potential to be used as a micronutrient fertilizer. Satisfactory results of grain yield (6.4 Mg ha-1), high content of micronutrients (Zn 1.6%, Mn 1.2%, and Cu 1.8%), and macronutrients (P 1.0%, S 3.1%, Ca 8.2%, and K 0.2%) were observed. The bioavailability suggests that enriched SMS could be a good alternative to fertilizers in the present market.


The coronavirus disease 2019 (COVID-19) pandemic has resulted in more than 900,000 deaths in the United States, disproportionately affecting racial and ethnic minorities. The pandemic is likely leading to disparate experiences of loss, though little research to date has examined disparities in experiences of loss from COVID-19. Drawing on a nationally representative survey of 6,000 first- and second-generation Latinx and Asian adults carried out in April and May 2021, this study reveals sharp disparities between and within ethnoracial groups in the United States in the experience of losing household members or close family and friends to COVID-19. Latinx adults were 1.65 times more likely than Asian adults to experience the loss of a loved one from COVID-19 (38 percent vs. 23 percent). First- and second-generation Indian Americans experienced disproportionately high rates of loss relative to other Asian Americans (33 percent). Looking both across and within ethnoracial categories is critical for understanding how the pandemic has compounded preexisting disadvantage.


Device parameter variations exhibit an increasingly serious impact on analog and mixed-signal circuit behavior. In this paper, we propose a novel fully-analog on-chip adaptive body bias calibration method, for efficiently reducing mismatches in transistor pairs. We present three circuit implementations which achieve a mismatch reduction between 61% and 73% in terms of standard deviation.


All robots create consequential sound—sound produced as a result of the robot's mechanisms—yet little work has explored how sound impacts human-robot interaction. Recent work shows that the sound of different robot mechanisms affects perceived competence, trust, human-likeness, and discomfort. However, the physical sound characteristics responsible for these perceptions have not been clearly identified. In this paper, we aim to explore key characteristics of robot sound that might influence perceptions. A pilot study from our past work showed that quieter and higher-pitched robots may be perceived as more competent and less discomforting. To better understand how variance in these attributes affects perception, we performed audio manipulations on two sets of industrial robot arm videos within a series of four new studies presented in this paper. Results confirmed that quieter robots were perceived as less discomforting. In addition, higher-pitched robots were perceived as more energetic, happy, warm, and competent. Despite the robot's industrial purpose and appearance, participants seemed to prefer more "cute" (or "kawaii") sound profiles, which could have implications for the design of more acceptable and fulfilling sound profiles for human-robot interactions with practical collaborative robots.


The Src family kinase Lyn initiates intracellular signal transduction by associating with a variety of immune receptors such as antigen receptor on B cells and high-affinity Fc receptor (FcR) for immunoglobulin Ig(E) (FcεRI) on mast cells. Involvement of Lyn in the IgE-mediated immediate-type hypersensitivity is well documented, but the physiological significance of Lyn in IgG-dependent, type III low-affinity FcR for IgG (FcγRIII)-mediated responses is largely unknown. In this study, we generated a double-mutant mouse strain deficient in both type II FcR for IgG (FcγRIIB) and Lyn to exclude any involvement of inhibitory signaling by FcγRIIB, which otherwise downregulates FcγRIII-mediated cellular responses. FcγRIIB-deficient but Lyn-sufficient mice served as controls. The Lyn deficiency attenuated IgG-mediated systemic anaphylaxis in vivo, and significantly reduced calcium mobilization and degranulation responses of bone marrow–derived mast cells (BMMCs) in vitro. However, we found that either interleukin 4 or tumor necrosis factor α release by BMMCs was comparable to that from Lyn-deficient and control mice, and the reverse-passive Arthus reaction was equally induced in both mutant mice, indicating that Lyn is not involved in the onset of the IgG-mediated, FcγRIII-dependent late phase responses of mast cells. These findings provide us with insight into distinct signaling mechanisms in mast cells underlying the development of diverse pathologies as well as a therapeutic potential for selective treatment of allergic disorders.


Background: Acyclovir and valacyclovir are used for the treatment and prophylaxis of infections with herpes simplex virus (HSV) and varicella zoster virus (VZV). The aim of this study is to provide insight into the pharmacodynamics (PD) of (val)acyclovir. Methods: Patients were retrospectively selected, based on therapeutic drug monitoring for acyclovir, to create a population pharmacokinetic (PK) model in Pmetrics. This PK model was used to develop a PK/PD model to study the effect of acyclovir levels on VZV viral load in plasma in immunocompromised patients. Results: Immunocompromised patients with known VZV viral loads in plasma were included for PK/PD modelling (N = 4, with 23 measure points); they were part of the population of 43 patients used for PK model building. The PK/PD model described the data well (r2 = 0.83). This is a hopeful first step in clarifying the pharmacodynamics of acyclovir; however, the data in this study are limited. Conclusions: Our preliminary PK/PD model can be used in further research to determine the effect of acyclovir levels on VZV viral load.


In today's era of globalization, the role of various sectors in the development of economy - namely, primary, secondary and tertiary - is changing day by day. As in the past, agriculture was the dominating sector in the countries like India but with rapid policy changes, the secondary and tertiary sectors seem to be gaining importance. Due to changes in the general level of affluence the indicators like per capita and GDP become the most important for development and with increasing product complexity and life expectancy, the tertiary sector is gaining more importance because of increased demand of services. So in the present paper we briefly examined the impact of sector-wide production and power consumption on the Gross State Domestic Product of Haryana using logit regression analysis and found that 1% change in primary sector production leads to 0.38% increase in GSDP; 1% change in secondary sector production leads to .48% change in GSDP; and 1% change in tertiary sector leads to .25% increase in GSDP. All three sectors are found to be statistically significant at 1% level of significance. The total paper is divided into five sections: the introduction, review of related literature, research methodology, data analysis and its interpretation, and the conclusion.


ABSTRACT This study investigates the potential beneficial effects of niacin (NA; vitamin B3) supplementation in rats chronically exposed to methylmercury (MeHg). Animals were randomly assigned to one of 4 groups (n = 6): Group I, control, received distilled water by gavage; Group II, received MeHg (100 µg/kg/d) by gavage; Group III, received NA (50 mg/kg/d) in drinking water; Group IV, received MeHg (100 µg/kg/d) by gavage + NA (50 mg/kg/d) in drinking water. Biochemical parameters levels of glucose, triglycerides, total cholesterol and fractions, and enzyme activities aspartate transaminase (AST) and alanine transaminase (ALT) were determined. Further, oxidative stress markers activity of glutathione peroxidase (GPx) and catalase (CAT) activity, as well as levels of reduced glutathione (GSH), malondialdehyde (MDA), and nitric oxide, were examined, and the comet assay was performed, using blood/plasma. Hg levels were measured in blood, brain, and kidneys of animals. Our results demonstrated that NA reduced adverse effects produced by MeHg. The mechanism underlying these effects appears to be related to the intrinsic antioxidant potential of NA. Considering the beneficial effects attributed to NA following MeHg exposure and that fish are the main source of both NA and MeHg, future studies need to evaluate the potential counteractive effect of NA against the adverse consequences of MeHg exposure in fish-eating populations.


Road traffic injuries (RTIs) cause a substantial disease burden in Vietnam. Evaluating health-related quality of life (HRQOL) among patients having a diversity of RTIs informs an integral part of treatment effectiveness. This study aims to examine HRQOL of patients suffering different RTIs in Vietnam's urban areas. A cross-sectional study was conducted on 408 patients from October to December 2018 in six hospitals in Thai Binh. The EuroQol-5 dimensions-5 levels (EQ-5D-5L) and visual analog scale (VAS) were used to assess the HRQOL of patients. Multivariable Tobit regression was applied to measure the difference of HRQOL among different kinds of injuries. The mean EQ-5D-5L and VAS score was 0.40–0.66, respectively. Mean EQ-5D-5L index was lowest in patients with oral and facial injuries (0.22) and fracture injuries (0.23), while patients having hand injuries had the highest EQ-5D-5L index (0.54). EQ-5D-5L index had a negative association with oral, facial, and fracture injuries. Meanwhile, patients with brain, fracture, and multiple injuries tended to have lower VAS score. Poor HRQOL among patients injured in road traffic were observed. Pain management, early rehabilitation, and mental health counseling services should be considered during treatment time, especially among those having the brain, oral and facial trauma, fracture, and multiple injuries.


The Advanced Solid-State Array Spectroradiometer (ASAS) is an airborne remote sensing instrument that acquires digital image data for 62 spectral channels in the visible and near-infared. It has an off-nadir tilting capability that has engendered its use as a tool for studying the bidirectional reflectance characteristics of Earth surfaces. Over the last three years, ASAS has undergone numerous upgrades that have resulted in increased data volumes and new data formats. A Unix-based processing system has been developed to decommutate, calibrate, analyze, and archive the ASAS digital imagery. In 1994, it will be tasked to process over 100 gigabytes of data to be acquired during field campaigns in Canada. This paper describes the ASAS processing system and the techniques involved in producing radiometrically calibrated data products for investigators.<<ETX>>


This article investigates factors that affect rejection rates in applications for outside finance among different types of investors (banks, venture capital funds, leasing firms, factoring firms, trade customers and suppliers, partners and working shareholders, private individuals and other sources), taking into account the non-randomness in a firm's decision to seek outside finance. The data support the traditional pecking order theory. Further, the data indicate that firms seeking capital are typically able to secure their requisite financing from at least one of the different available sources. However, external finance is often not available in the form that a firm would like. Copyright © The Author(s). Journal compilation © Royal Economic Society 2009.


Fine transverse folds can be seen by double contrast technique in the human esophagus which are similar to those seen regularly in the feline esophagus. These folds are transient in nature and possibly represent contraction of the muscularis mucosae. This fold pattern can be seen in patients with gastroesophageal reflux and in those with no symptoms of esophageal disease. The marginal serration should not be mistaken for diffuse ulceration on barium filled views of the esophagus. Distortion of interruption of the normal fold pattern can be seen in patients with superficial ulceration due to reflux esophagitis or other invasive mucosal lesions. Although the pathophysiologic significance of this phenomenon is uncertain, the demonstration and recognition of these folds allows for better definition of mucosal surface abnormalities.


Social influence has been widely accepted to explain people's cascade behaviors and further utilized in many related applications. However, few of existing work studied the direct, microscopic and temporal impact of social influence on people's behaviors in detail. In this paper we concentrate on the behavior modeling and systematically formulate the family of behavior propagation models (BPMs) including the static models (BP and IBP), and their discrete temporal variants (DBP and DIBP). To address the temporal dynamics of behavior propagation over continuous time, we propose a continuous temporal interest-aware behavior propagation model, called CIBP. As a new member of the BPM family, CIBP exploits the continuous-temporal functions (CTFs) to model the fully-continuous dynamic variance of social influence over time. Experiments on real-world datasets evaluated the family of BPMs and demonstrated the effectiveness of our proposed approach.


Transgenic mice are useful tools to investigate the mechanisms of the renal profibrotic actions of endothelin and angiotensin II. The overexpression of angiotensinogen and renin genes induces renal sclerosis independently of changes in systemic hemodynamics. The same results are observed when the endothelin-1 gene is overexpressed. Transgenic mice harboring the luciferase gene, under the control of the collagen I alpha2 chain promoter, and made hypertensive by induction of a nitric oxide (NO) deficiency have been studied. In this strain of mice, luciferase activity is an early index of renal and vascular fibrosis. Luciferase activity was increased in preglomerular arterioles and glomeruli when mice were treated with N:(omega)-nitro-L-arginine methyl ester, an inhibitor of NO synthases. Bosentan (an endothelin receptor antagonist) was as efficient as losartan (an AT1 receptor antagonist) in preventing renal fibrosis, although it did not decrease BP. In short-term experiments, angiotensin II produced an increase in luciferase activity that was entirely prevented by losartan but also by bosentan. It can be concluded that, during chronic inhibition of NO, the collagen I gene is activated, which contributes to the development of nephroangiosclerosis and glomerulosclerosis. Angiotensin II plays a major role in this fibrogenic process, and its effect is at least partly independent of systemic hemodynamics and mediated by the profibrotic action of endothelin-1.


Acute myeloid leukemia (AML) is a highly heterogeneous disease with numerous signaling pathways that contribute to its pathogenesis. Advances in our understanding of molecular mechanisms of AML pathogenesis and prognosis so far did not translate into significant clinical improvements. AML is still the highest unmet medical need within hematological malignancies area, particularly in case of the elderly patients. FLT3 inhibitors were investigated in the recent years as possible therapeutic agents, however to date the clinical trials of FLT3 inhibitors have yielded disappointing results. On the other hand, PIM kinases have been identified in the last years as critical downstream components of FLT3 signaling, especially in the case of oncogenic FLT3 mutants. PIM kinases are being overexpressed in a range of hematopoietic malignancies and solid cancers and the overexpression of PIMs is associated with a poor prognosis and decreased survival of patients suffering from cancer. In many cases also, PIM overexpression was associated with development of drug resistance. As dual and simultaneous inhibition of various pathway components is an emerging therapeutic idea, exemplified by several compounds in development for cancer treatment, we have developed a series of dual PIM/FLT3 small molecule inhibitors to investigate this concept. Similarly to examples of small molecule inhibitors from the JAK/STAT or PI3K/AKT pathways, where compounds are being developed as a way to improve efficacy, resistance development and overcoming the negative feedback loops, often seen after single target inhibition, we have observed increased potency of compounds developed in this series of dual PIM/FLT3 inhibitors. Synthesized inhibitors showed higher activity towards mutated FLT3 (FLT3-ITD and other FLT3 mutants) than wild type kinase and the selectivity profile on a panel of 450 kinases was comparable to best clinical examples of kinase inhibitors. In contrast to selective PIM inhibitors, the treatment with dual PIM/FLT3 inhibitors showed potent apoptosis induction as a results of Erk and S6 phosphorylation inhibition. The in vitro activity in FTL3-ITD positive cells was also confirmed in vivo in a PK/PD xenograft experiment, where sustained biomarker inhibition was observed already after single compounds administration. Oral administration of dual PIM/FLT3 inhibitors led to potent effect in vivo and in certain cases also to remissions in subcutaneous xenograft models. Observed activity profile and synergistic effects observed with other targeted therapies and standard of care compounds, makes dual PIM/FLT3 inhibitors an exciting approach for treatment of FLT3-mutant positive AML patients with high chances of clinical success. Citation Format: Wojciech Czardybon, Michal Galezowski, Renata Windak, Magdalena Salwinska, Izabela Dolata, Ewa Trebacz, Radoslaw Obuchowicz, Pawel Guzik, Magdalena Zawadzka, Ewelina Wincza, Katarzyna Wiklik, Mariusz Milik, Malgorzata Zurawska, Karolina Krawczynska, Krzysztof Brzozka. Identification of potent, dual PIM/FLT3 kinase inhibitors for AML treatment. [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 3245. doi:10.1158/1538-7445.AM2013-3245


This article uses the case of Ivory Coast as a starting point to present some considerations regarding the influence of international education norms in an education system which is recovering from a series of crises. After a historical overview of the internationalization of the system, the study focuses on the post-conflict era. The results are based on a literature review, as well as on empirical data, which draws on interviews, questionnaires and workshops organized with the school system's technical and financial partners between April 2012 and October 2013 in Abidjan, and in central and western Ivory Coast. The article shows that the presence of international organizations legitimizes the current government's actions. As a result, international aid is frequently sought out and highly valued. The education system has been rebuilt, developed and transformed under the influence of international organizations. The public authorities do not perceive this as a form of interference, and nor do the parents, teachers, school children, high-school students, and university students, as a consequence of the singular situation in which the State and the civil society are in this post-conflict era.


The use of fibres to reinforce brittle materials for
better performance has been employed since time immemorial.
Therefore, inclusion of steel fibres in concrete has always
improved the post-cracking strength and concrete ductility to a large extent while full potential of steel fibre reinforced
concrete (SFRC) is still yet to be exploited in practice. This study investigated the effects of fibre type, dosage and
maximum aggregate size on distribution and orientation and
hence, the flexural performance of steel fibre reinforced
concrete. Hooked-end steel fibres with 50 mm and 60 mm
length, aspect ratio of 45, 65 and 80, and dosages of 0 kg/m³, 25 kg/m³, 40 kg/m³, 50 kg/m³ and 60 kg/m³ were used with maximum sizes of coarse aggregate of 10mm and 20mm. X-ray Computed Tomography was employed for imaging cores taken
from the slab specimens after testing. The experimental results show a remarkable improvements in flexural strength up to 83% observed at larger dosage of steel fibre and when good interaction leading to better distribution and orientation of fibres within concrete matrix is sustained between right fibre geometry and appropriately sized aggregate.