Background: The non-interventional study CONIFER was designed to assess the safety and clinical practicability of deferasirox for the treatment of transfusional iron overload in myelodysplastic syndrome (MDS) patients. Methods: Patients included in the study were diagnosed with MDS and received at least 1 treatment with deferasirox. The observation period covered the time from the initial visit until the last follow-up. Results: The data of 99 patients with MDS scored mainly as International Prognostic Scoring System (IPSS) low and intermediate 1 were evaluated. The mean age of the participants was 75 years and 58% of the patients were male. Iron overload was assessed by serum ferritin level (mean baseline serum ferritin 2,080 ± 1,244 µg/l). Patients were treated for a mean duration of 16 months (mean daily dose at baseline 11.8 ± 7.0 mg/kg). Stratification of serum ferritin levels by deferasirox dose showed a reduction at the higher but no reduction at the lower dose (< 15 mg/kg vs. ≥ 15 mg/kg and < 20 mg/kg vs. ≥ 20 mg/kg). The majority of patients (81%) were affected by at least 1 adverse event, with decreased renal creatinine clearance being the most frequent. Conclusion: Higher doses (≥ 15 mg/kg) of deferasirox effectively and safely reduced serum ferritin levels in MDS patients with transfusional iron overload.


This study intends to find a relation between children´s perceived restoration and their environmental orientations. In order to do that, a designed perceived restoration scale adapted from the PRCS-C II was used as well as an adapted version of the Children´s Environmental Perceptions Scale (CEPS). A total of 832 children aged between 6 and 13 participated in the study. The results show that there is a relation between the perceived restoration due to the nature present in the school playground and the environmental orientations children show.
Keywords:    Children, environmental orientations, perceived restoration, nature.
© 2017 The Authors. Published for AMER ABRA by e-International Publishing House, Ltd., UK. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Peer–review under responsibility of AMER (Association of Malaysian Environment-Behaviour Researchers), ABRA (Association of Behavioural Researchers on Asians) and cE-Bs (Centre for Environment-Behaviour Studies), Faculty of Architecture, Planning & Surveying, Universiti Teknologi MARA, Malaysia.


The classic Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPNs) are a heterogeneous group of hematopoietic stem-cell diseases, characterized by activated JAK/STAT signaling and significant phenotypic mimicry, including a propensity for evolution to myeloid blast phase disease. Effective therapeutic options are limited for patients with Ph- MPNs in the blast phase (MPN-BP), and allogeneic stem-cell transplantation is the only known cure. Our increasing understanding of the molecular pathogenesis of this group of diseases, coupled with the increasing availability of targeted agents, has the potential to inform new subset-specific therapeutic approaches. Ultimately, progress in MPN-BP will hinge on prospective clinical and translational investigations with the goal of generating more effective treatment interventions. This case-based review highlights the molecular and clinical heterogeneities of MPN-BP and incorporates a treatment algorithm that underscores the importance of a personalized approach to this challenging group of diseases.


The syntheses and RNA cleavage efficiencies of a new series of oligonucleotide conjugates of Cu(II)-serinol-terpyridine and 1,3-propanediol are reported. These reagents, termed ribozyme mimics, were designed such that they would yield multiple unpaired RNA residues directly opposite the site of the RNA cleavage catalyst upon ribozyme mimic-RNA duplex formation. This design effect was implemented using the 1,3-propanediol linker 3, which mimics the three-carbon spacing between the 5'- and 3'-hydroxyls of a natural nucleotide. Incorporation of one or more of these 1,3-propanediol linkers at positions directly adjacent to the serinol-terpyridine modification in the ribozyme mimic DNA strand resulted in cleavage at multiple phosphates in a complementary 31-mer RNA target sequence. The linkers effectively created artificial mismatches in the RNA-DNA duplexes, rendering the opposing RNA residues much more susceptible to cleavage via the transesterification/hydrolysis pathway. The RNA cleavage products produced by the various mimics correlated directly with the number and locations of the linkers in their DNA strands, and the most active ribozyme mimic in the series exhibited multiple turnover in the presence of excess 31-mer RNA target.


The structure of melt-spun nylon 6 filaments was studied using on-line x-ray diffraction and birefringence measurements. Measurements were also made on as-spun and treated filaments. On-line wide-angle x-ray scattering measurements indicated that crystallization did not occur on the nylon 6 spinline at spinning rates up to 1000 m/min when spinning was done into either ambient air of 60% relative humidity or into wet saturated air. The filaments did crystalline gradually on the bobbin to a paracrystalline pseudohexagonal (γ) form. The rate of crystallization was dependent on the molecular orientation developed in the spun filaments. Crystalline orientation factors based on hexagonal symmetry were computed as a function of take-up velocity for fibers which were conditioned 24 hr in air at 65% relative humidity. Annealing in air or treatment in water or 20% formic acid solution causes a transformation from the pseudohexagonal form to the α monoclinic form. The tangent modulus of elasticity and tensile strength of spun and conditioned filaments increase with increasing take-up velocity and spinline stress, while elongation to break decreases with these variables.


Cerebrovascular accidents (CVA) are important causes of neurological clinical signs in dogs. The objective of this work was to describe concurrent diseases and ultrasonographic features in dogs with CVA confirmed through postmortem evaluation. All medical records of transcranial Doppler ultrasonography (TCDUS) examinations performed in 512 dogs between 2007 and 2009 were reviewed, searching for history and clinical diagnosis, as well as sonographic and histological results. Forty-two dogs were selected, showing acute onset of clinical signs with no progressive focal cerebral dysfunction and diagnosis of cerebrovascular disease confirmed at necropsy. Concurrent diseases and conditions were: cerebral amyloid microangiopathy (33%), endocrinopathies (31%), coagulopathy (24%), Schnauzer hyperlipemia (7%) and unknown (5%). The relation between sonography and histology results indicated 100% sensitivity and 90% specificity for focal lesion detection. A diffuse decrease in echogenicity was related to inflammatory diseases and/or edema with 62% sensitivity. A diffuse increase in echogenicity has 100% sensitivity and was usually related to aging changes. This study showed the occurrence of coexisting diseases with CVA and sonographic features of these conditions in small breed dogs.


The current method for determining shot peening intensities and to verify process parameters in production is to use Almen strips and saturation curves. Even though it is a well established process it still has some disadvantages. For example, measurements can not be stored over a longer period of time due to relaxation of the material, online intensity verification is not possible and the whole process itself can be quite time consuming, depending on the complexity of the part to be peened. In order to find another process which can be used more conveniently, intensity verification by means of velocity measurement of the peening media was investigated. Different parameters which are known to influence the peening intensity were varied and their effects on the shot velocity were documented. Pressure, shot flow, type of nozzle, type of peening media, as well as hose bending and peening angle are among the variables tested. Two different methods of velocity measurement were used and compared with one another. A long-term study under production conditions was carried out to test the stability and reliability of the measurement process. Based on the results, the potentials of the velocity measurement were identified and possibilities were explored to include this process in production as a substitute for or alternative to Almen strip measurement.


______ Abstract Staging processes and choreographies of contemporary dance and performance: do they have to be perceived as a mere passing of choreographic notations from a single choreographer to dancers who have to repeat them "mindlessly" (Laermans 2015, 196)? Or should these rather be discussed as a reciprocal situation providing aesthetic experiences for participants in a singular-plural mode? To put it differently: Might choreography have the capacity to create an environment for the refinement of a democratic grass-roots consciousness? In order to discuss these questions, I have adapted various scientific perspectives in my research (Julian, forthcoming, autumn 2021). The starting point of my studies lies in theatre studies based on comparative methods. Artistic practices are juxtaposed in order to highlight their specificity. In a second step––inspired by the discourse as developed in theatre studies (Tatari 2017; Ruhsam 2011) ––I discussed staging processes in conjunction with an ontological principle as conceptualised by the philosopher Jean-Luc Nancy (2000): the specificity of being-with makes it possible to theorise a range of infinite possibilities and differences that evolve by the mere execution of movement patterns. The third perspective is based on sociological methods that were adapted in order to embed the staging process in real-life conditions. My consideration here is that only by knowing imbalances that may exist in social life we understand the dynamics unfolding throughout a group that gathers in order to create a piece. The fourth perspective I apply in this article is based on a method called the aesthetic field as conceived by the philosopher Arnold Berleant (1970): having similarities to being-with makes it possible to cover not merely human interactions and social conditions but also interactions and permeations with a thing world, such as architectures, a stage design, costumes. Thus, the thing world can be seen as co-choreographing the work.


This study examined the effect of dissolved organic matter (DOM) on ectoenzymatic activity, bacterial growth and community structure in the Hudson River. Our main approach was to mix bacterial communities and water from various locations in the Hudson River and its tributaries, and then to monitor bacterial activity and community structure determined by fluorescence in situ hybridization with oligonucleotide probes. The locations differed significantly in DOM composition and concentrations, ectoenzyme activity and bacterial community structure. We found that water source and, to a lesser extent, source of the inoculum significantly affected nearly all aspects of bacterial activity and community structure. A common inoculum grown in different waters often led to as much as a 2-fold difference in enzyme activities. When 2 different bacterial communities were inoculated in the same water, community structure and the activity of some ectoenzymes remained different after several days. Other data also pointed to a dependence of ectoenzyme activity on community structure. Activity of several ectoenzymes covaried with the relative abundances of the 4 bacterial groups we examined (alpha-, beta- and gamma-proteobacteria, and Cytophaga-like bacteria); the highest correlation was between beta-proteobacteria and phosphatase activity. In multi-variate regression analyses, community structure explained a significant amount of the variation in rates of all ectoenzymes except 2 proteases. The abundance of Cytophaga-like bacteria was the dominant variable in the regression models for the activity of 3 ectoenzymes. These data suggest that DOM can affect the relative abundance of the major heterotrophic bacterial groups, and that the relative abundance of these groups could have an impact on DOM hydrolysis.


Architected materials are materials engineered to utilize their topological aspects to enhance the related physical and mechanical properties. With the witnessed progressive advancements in fabrication techniques, obstacles and challenges experienced in manufacturing geometrically complex architected materials are mitigated. Different strut-based architected lattice structures have been investigated for their topology-property relationship. However, the focus on lattice design has recently shifted toward structures with mathematically defined architectures. In this work, we investigate the architecture-property relationship associated with the possible configurations of employing the mathematically attained Schoen's I-WP (IWP) minimal surface to create lattice structures. Results of mechanical testing showed that sheet-based IWP lattice structures exhibit a stretching-dominated behavior with the highest structural efficiency as compared to other forms of strut-based and skeletal-based lattice structures. This study presents experimental and computational evidence of the robustness and suitability of sheet-based IWP structures for different engineering applications, where strong and lightweight materials with exceptional energy absorption capabilities are required.


This study focuses on the influence of surface treatment and fibre sizes on mechanical behavior, physical properties and morphology of rice husk fibre (RHF) reinforced polylactic-acid (PLA). Modified RHF was prepared by using 6w.t.% sodium hydroxide (NaOH) and distilled water. PLA composite reinforced with 25w.t.% volume fractions of modified RHF was mixed using the internal mixer and fabricated by the mini injection moulding. Tensile and flexural strength results showed that the PLA composite with 100, 200 and 500μm particles sizes of water treated fibre are much higher than those of alkaline treated. DSC measurement was performed and indicated that the Tg, Tm and ΔHm of PLA reduced after reinforcement with water treated and alkaline treated fibres. TGA results showed that the treatment reduced the thermal stability of the PLA. FESEM micrographs for flexural fractured surfaces of composites showed micro crack and pores due to brittle fracture of the PLA matrix adjacent to the fibre as a result of the brittle nature of the PLA resin.


Aim: Gradients of environmental heterogeneity perform a strong influence on the distribution of organisms and determine differences in composition, where more physically complex habitats harbor greater species richness than those simpler. We took as assumptions that differences in environmental requirements of taxa promote distinct distribution patterns which are carried through to community nestedness. Therefore, we hypothesized that more heterogeneous sites hold more nested, richer and abundant communities than those less heterogeneous ones. Methods: We analyzed Chironomidae occurrence of 29 floodplain lakes, through one-year-surveys. Analyses of variance were performed to test differences among data. To test our hypothesis, we calculated correlations between the gradients of environmental heterogeneity and Chironomidae metacommunity. Results: Highest values in all Chironomidae attributes were recorded in general to the floodplain lakes from Paraná System, mainly in September. Positive correlation between all Chironomidae attributes (i.e, richness, density, Biodiversity score and NODF index) both with PCA scores and variation coefficient values supported our initial hypothesis about the importance of environmental heterogeneity in metacommunity assembly. Conclusions: We have demonstrated how differences in environmental heterogeneity promote the nestedness in floodplain lakes and the importance of more heterogeneous places in supporting richer and more abundant communities in species. Such results contribute to future studies on composition and richness of Chironomidae community in other kind of environments. Nested distribution suggests that, despite the existence of floodplain lakes including most of the Chironomidae richness, considering the dispersal ability of species and environmental requirements, there is a strong interaction between all environments of the area. Therefore, areas that have locations with different patterns of richness and composition are critical to maintaining the diversity of the group at the landscape level.


Background Preoperative radiological imaging in pectus excavatum sometimes coincidentally yields additional intrathoracic abnormalities. In the context of a larger research project investigating replacement of CT scans by 3D-surface scanning as routine preoperative work-up for pectus excavatum, this study aims to quantify the incidence of clinically relevant intrathoracic abnormalities found incidentally using conventional CT in pectus excavatum patients. Methods A single-center retrospective cohort study was conducted including pectus excavatum patients, receiving CT between 2012 and 2021 as part of their preoperative evaluation. Radiology reports were reviewed for additional intrathoracic abnormalities and scored into three subclasses: non-clinically relevant, potentially clinically relevant or clinically relevant findings. Also, two-view plain chest radiographs reports, if available, were evaluated for those patients with a clinically relevant finding. Subgroup analysis was performed to compare adolescents and adults. Results In total, 382 patients were included, of whom 117 were adolescents. Although in 41 patients (11%) an additional intrathoracic abnormality was found, only two patients (0.5%) presented with a clinically relevant abnormality requiring additional diagnostics, postponing surgical correction. In only one of the two patients, plain chest radiographs were available, which did not show the abnormality. Subgroup analyses revealed no differences in (potentially) clinically relevant abnormalities between adolescents and adults. Conclusions The prevalence of clinically relevant intrathoracic abnormalities in pectus excavatum patients was low, supporting the notion that CT and plain radiographs can be safely replaced by 3D-surface scanning in the preoperative work-up for pectus excavatum repair.


Induction of DNA damage triggers a complex biological response concerning not only repair systems but also virtually every cell function. DNA topoisomerases regulate the level of DNA supercoiling in all DNA transactions. Reverse gyrase is a peculiar DNA topoisomerase, specific to hyperthermophilic microorganisms, which contains a helicase and a topoisomerase IA domain that has the unique ability to introduce positive supercoiling into DNA molecules. We show here that reverse gyrase of the archaean Sulfolobus solfataricus is mobilized to DNA in vivo after UV irradiation. The enzyme, either purified or in cell extracts, forms stable covalent complexes with UV-damaged DNA in vitro. We also show that the reverse gyrase translocation to DNA in vivo and the stabilization of covalent complexes in vitro are specific effects of UV light irradiation and do not occur with the intercalating agent actinomycin D. Our results suggest that reverse gyrase might participate, directly or indirectly, in the cell response to UV light-induced DNA damage. This is the first direct evidence of the recruitment of a topoisomerase IA enzyme to DNA after the induction of DNA damage. The interaction between helicase and topoisomerase activities has been previously proposed to facilitate aspects of DNA replication or recombination in both Bacteria and Eukarya. Our results suggest a general role of the association of such activities in maintaining genome integrity and a mutual effect of DNA topology and repair.


Intensity inhomogeneity occurs when pixels in medical images overlap due to anomalies in medical imaging devices. These anomalies lead to difficult medical image segmentation. This study proposes a new active contour model (ACM) with fractional sinc function to inexpensively segment medical images with intensity inhomogeneity. The method integrates a nonlinear fractional sinc function in its curve evolution and edge enhancement. The fractional sinc function contributes in giving a rapid contour movement where it improves the curve's bending capability. Furthermore, the fractional sinc function enables the contour evolution to move toward the object based on the preserved edges. This study uses the proposed method to segment medical images with intensity inhomogeneity using five various image modalities. With improved speed, the proposed method more accurately segments medical images compared with other baseline methods.


The interferometric coherence map derived from the cross-correlation of two complex registered synthetic aperture radar (SAR) images is the reflection of imaged targets. In many applications, it can act as an independent information source, or give additional information complementary to the intensity image. Specially, the statistical properties of the coherence are of great importance in land cover classification, segmentation and change detection. However, compared to the amount of work on the statistical characters of SAR intensity, there are quite fewer researches on interferometric SAR (InSAR) coherence statistics. And to our knowledge, all of the existing work that focuses on InSAR coherence statistics, models the coherence with Gaussian distribution with no discrimination on data resolutions or scene types. But the properties of coherence may be different for different data resolutions and scene types. In this paper, we investigate on the coherence statistics for high resolution data over urban areas, by making a comparison of the accuracy of several typical statistical models. Four typical land classes including buildings, trees, shadow and roads are selected as the representatives of urban areas. Firstly, several regions are selected from the coherence map manually and labelled with their corresponding classes respectively. Then we try to model the statistics of the pixel coherence for each type of region, with different models including Gaussian, Rayleigh, Weibull, Beta and Nakagami. Finally, we evaluate the model accuracy for each type of region. The experiments on TanDEM-X data show that the Beta model has a better performance than other distributions.


In humans overlap between various neurodegenerative disorders is a well known phenomenon. We reported a case of a 77-year-old woman with parkinsonism, dystonia, psychiatric symptoms and progressing dementia misdiagnosed at the age of 51 years as Parkinson's disease. Histopathological examination of the patient's brain performed 26 years after the disease onset revealed numerous axonal spheroids and iron deposits in structures of the nigro-pallido-striatal system that enabled to diagnose neurodegeneration with brain iron accumulation (NBIA) (former Hallervorden-Spatz syndrome), and changes characteristic for Alzheimer's disease (AD). NBIA is a group of rare clinically and genetically heterogeneous diseases of the extrapyramidal system which common feature is abnormal iron storage in the basal ganglia. Disturbed iron metabolism is also one of the hypothetical patho-mechanisms of AD. A coexistence of morphological changes characteristic for AD and NBIA in our patient suggests that similar molecular mechanisms may be involved in pathogenesis of various neurodegenerative processes, especially in disorders with iron dyshomeostasis. This case contributes also to the increasing evidence of NBIA heterogeneity.


Concomitant to the analysis of poverty is the measurement of vulnerability. Estimates of household vulnerability to income poverty are developed using a modified probit model that considers volatilities in income as being explained by some household characteristics. Resulting vulnerability estimates are found to be higher than poverty rates, suggesting that policy interventions will have to be developed to minimize the risk households face in becoming income poor, or at least help them in mitigating the impact of their becoming poor.


Pervasive computing aims to build an aggregated environment around a user by knitting diverse computing and communicating devices and software services into a single homogeneous unit. Our work is to develop a Pervasive computing framework which harnesses the power of Semantic Web and Web Services, facilitating the development of effective and intelligent Pervasive environments. This paper presents a high level view of the framework and how different Pervasive services can be built on this framework.


For complex System-on-chips (SoCs) fabricated in nanometer technologies, the system-level on-chip communication architecture is emerging as a significant source of power consumption. Managing and optimizing this important component of SoC power requires a detailed understanding of the characteristics of its power consumption. Various power estimation and low-power design techniques have been proposed for the global interconnects that form part of SoC communication architectures (e.g., low-swing buses, bus encoding, etc). While effective, they only address a limited part of communication architecture power consumption. A state-of-the-art communication architecture, viewed in its entirety, is quite complex, comprising several components, such as bus interfaces, arbiters, bridges, decoders, and multiplexers, in addition to the global bus lines. Relatively little research has focused on analyzing and comparing the power consumed by different components of the communication architecture. In this work, we present a systematic evaluation and analysis of the power consumed by a state-of-the-art communication architecture (the AMBA on-chip bus), using a commercial design flow. We focus on developing a quantitative understanding of the relative contributions of different communication architecture components to its power consumption, and the factors on which they depend. We decompose the communication architecture power into power consumed by logic components (such as arbiters, decoders, bus bridges), global bus lines (that carry address, data, and control information), and bus interfaces. We also perform studies that analyze the impact of varying application traffic characteristics, and varying SoC complexity, on communication architecture power. Based on our analyses, we evaluate different techniques for reducing the power consumed by the on-chip communication architecture, and compare their effectiveness in achieving power savings at the system level. In addition to quantitatively reinforcing the view that on-chip communication is an important target for system-level power optimization, our work demonstrates (i) the importance of considering the communication architecture in its entirety, and (ii) the opportunities that exist for power reduction through careful communication architecture design.


Beetles (Coleoptera) are the most common insects recovered from the Lower Jurassic Mintaja insect locality of Western Australia, with over half of the fossils recorded from this site being isolated coleopteran elytra. A range of partial beetle bodies and other isolated beetle sclerites have also been recovered from the locality; much of this material is taxonomically unidentifiable due to its disarticulation and poor preservation. A number of the Mintaja coleopterans are assigned to the archostematan family Ommatidae, including Zygadenia westraliensis (Riek, 1968) comb. nov, previously placed in the morphogenus Mesothoris, and an unnamed species of Tetraphalerus. Also recorded is a new species of elaterid, Lithomerus wunda sp. nov., along with other fragments likely attributable to the same family. The remaining material is assigned into morphospecies, separated primarily on preserved body parts — specifically, there are three morphospecies based on partially articulated coleopteran bodies, two morphospecies based on isolated head capsules, three morphospecies based on isolated thoracic sclerites, three morphospecies based on isolated abdominal sclerites, and 13 morphospecies based on isolated elytra. Overall, the ecology of these fossils is difficult to interpret due to poor preservation, although some of the beetles were likely aquatic, and the Ommatidae and Elateridae were both likely xylophilous. There is a strong similarity between the Mintaja coleopterans and those from the Late Triassic Denmark Hill locality of Queensland, though many of these similarities are based on morphotaxa and may be superficial in nature. Of the species that have been assigned to named taxa, all are generally typical of the Late Mesozoic worldwide, with Zygadenia, Tetraphalerus and Lithomerus all long‐ranging, cosmopolitan genera.


Canonically, MST1/2 functions as a core kinase of the Hippo pathway and non-canonically is both activated during apoptotic signaling and acts in concert with RASSFs in T-cells. Faithful signal transduction relies on both appropriate activation and regulated substrate phosphorylation by the activated kinase. Considerable progress has been made understanding the molecular mechanisms regulating activation of MST1/2 and identifying downstream signaling events. Here we present a kinetic analysis analyzing how the ability of MST1/2 to phosphorylate substrates is regulated. Using a steady state kinetic system, we parse the contribution of different factors including the domains of MST2, phosphorylation, caspase cleavage, and complex formation to MST2 activity. In the unphosphorylated state, we find the SARAH domain stabilizes substrate binding. Phosphorylation, we also determine, drives activation of MST2 and that once activated the kinase domain is free of regulation. The binding partners SAV1, MOB1A, and RASSF5 do not alter the kinetics of phosphorylated MST2. We also show that the caspase cleaved MST2 fragment is as active as full-length suggesting that the linker region of MST2 does not inhibit the catalytic activity of the kinase domain but instead regulates MST2 activity through non-catalytic mechanisms. This kinetic analysis helps establish a framework for interpreting how signaling events, mutations, and post-translational modifications contribute to signaling of MST2 in vivo.


This paper presents the evaluation of cytoprotective ability of trehalose-based eye drops in comparison with commercially available preparations during the experimental desiccation of cultured human corneal epithelial cells. Cultured human corneal epithelial cells (hCEC) underwent incubation with 7 different, commercially available medicaments used commonly in dry eye syndrome treatment, followed by desiccation trial performed on air under the flow hood for 5, 15, 30, and 45 minutes. Cell viability was quantified by live/dead fluorescent assay, while the presence of apoptotic cells was estimated by immunofluorescent staining for active caspase 3 protein. The preservation of membrane functions was evaluated using neutral red staining, while the preservation of proper morphology and phenotype was determined by fluorescent staining for actin filaments, nuclei, and p63 protein. The trehalose-based eye drops showed the highest efficiency in prevention of cell death from desiccation; moreover, this preparation preserved the normal cellular morphology, functions of cell membrane, and proliferative activity more effectively than other tested medicaments.


The theorem of P. Fong about a splitting field of representations of a finite group G will be improved to the effect that the order of G mentioned in it will be replaced by the exponent of G. The proof depends on the Brauer-Witt theorem and properties of cyclotomic algebras.


This paper investigates the effects of inhomogeneity and anisotropy on the EEG forward problem using spherical head models. The role of skull and brain anisotropy along with the effects of inhomogeneity in different layers of the spherical volume conductor have been quantified, numerically and analytically, using statistical modalities such as RDM, MAG and CC. The paper also investigates the effect of mesh density, selection of element type and role of adaptive mesh refinement on the accuracy and convergence of the finite element method.


As the demand for liquefied natural gas increases globally there are many local emerging markets arising but the technology and the infrastructure is capital intensive. The plants include many piping solutions which need to be designed specifically for this kind of application. The objective of this work is to evaluate the potential of using a pre – insulated pipe dimensioning model, developed for Uponor Infra Oy, a market leading Finnish company in piping infrastructure manufacturing, for liquefied natural gas applications. The methods used during the study were research and mathematics based including researching European standards on pre – insulated piping and thermodynamic calculations to establish the method of calculating thermodynamic properties of pre – insulated pipes. The results indicate that there is a potential in using pre – insulated pipe dimensioning calculation methods for liquefied natural gas applications.


This article offers perspectives into some of the key intersections between ethics in representation and game design by showcasing an extended ten-minute version of the presenters' original video about the provocation of visual ethics in gaming, first shown at the summit 'Re/Sponse-able Visual Ethics.' This version particularly divulges further detail into the ludic and congruent real-world dynamics that come into play in coding and facilitating both the game's system of rules and mechanics as well as the player's immersion in its game world. Topics principally addressed included the relationship and function of violence in procedural-based game activity, and game developer intentions or responses to their chosen subjects and themes embedded into their game. While the video and its topics primarily aligned to the presenters' respective disciplines, it is still a valuable platform to instigate new or expand existing avenues of research into the relationship of ethics and gaming.


The widespread of ransomware experienced in the last years has been caused also by the ability of attackers to introduce changes and mutations that make the malware hard to identify from antimalware software. In this paper we propose a two-phase method based on machine learning on API-level analysis aimed (i) to effectively detect ransomware despite the applied techniques for obfuscation and introduced variations, (ii) to provide a tool for security analysts to track phylogenetic relationships exploiting the binary tree obtained by the classification analysis. We preliminary experimented the proposed method on real-world ransomware applications belonging to three widespread families (i.e., petya, badrabbit and wannacry), obtaining encouraging results in ransomware detection and family identification. A discussion about the ransomware-related phylogenetic relationships is also provided.


The robustness principle, written by Jon Postel in an early version of TCP implementation, states that the communicating entities should be liberal while accepting the data. Several entities on the Internet do follow this principle. For instance, in this work, we show that many popular web servers on the Internet are generous as they wait for a substantial time period to receive the remaining portion of an incomplete web request. Unfortunately, this behavior also makes them vulnerable to a class of cyber attacks, commonly known as Slow Rate DoS attacks. HTTP/2, the recent version of HTTP, is recently found vulnerable to these attacks. However, the impact of Slow HTTP/2 DoS attacks on real web servers on the Internet has not been studied yet. Also, to the best of our knowledge, there is no defense scheme known to detect Slow Rate DoS attacks against HTTP/2 in real-time. To bridge these gaps, we first test the behavior of HTTP/2 supporting web servers on the Internet against Slow HTTP/2 DoS attacks. Subsequently, we propose a scheme to detect these attacks in real-time. We show that the proposed detection scheme can detect attacks in real-time with high accuracy and marginal computational overhead.


Background: Necroptosis has been an alternatively identified mechanism of programmed cancer cell death, which plays a significant role in cancer. However, research about necroptosis-related long noncoding RNAs (lncRNAs) in cancer are still few. Moreover, the potentially prognostic value of necroptosis-related lncRNAs and their correlation with the immune microenvironment remains unclear. The present study aimed to explore the potential prognostic value of necroptosis-related lncRNAs and their relationship to immune microenvironment in triple-negative breast cancer (TNBC). Methods: The RNA expression matrix of patients with TNBC was obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Finally, 107 patients of GSE58812, 159 patients of TCGA, and 143 patients of GSE96058 were included. Necroptosis-related lncRNAs were screened by Cox regression and Pearson correlation analysis with necroptosis-related genes. By LASSO regression analysis, nine necroptosis-related lncRNAs were employed, and a cell necroptosis index (CNI) was established; then, we evaluated its prognostic value, clinical significance, pathways, immune infiltration, and chemotherapeutics efficacy. Results: Based on the CNI value, the TNBC patients were divided into high- and low-CNI groups, and the patients with high CNI had worse prognosis, more lymph node metastasis, and larger tumor (p < 0.05). The receiver operating characteristic (ROC) analysis showed that the signature performed well. The result of the infiltration proportion of different immune cell infiltration further explained that TNBC patients with high CNI had low immunogenicity, leading to poor therapeutic outcomes. Moreover, we found significant differences of the IC50 values of various chemotherapeutic drugs in the two CNI groups, which might provide a reference to make a personalized chemotherapy for them. Conclusion: The novel prognostic marker CNI could not only precisely predict the survival probability of patients with TNBC but also demonstrate a potential role in antitumor immunity and drug sensitivity.


Gentamicin (GEN) is a kind of aminoglycoside antibiotic with the adverse effect of nephrotoxicity. Currently, no effective measures against the nephrotoxicity have been approved. In the present study, epigallocatechin gallate (EG), a useful ingredient in green tea, was used to attenuate its nephrotoxicity. EG was shown to largely attenuate the renal damage and the increase of malondialdehyde (MDA) and the decrease of glutathione (GSH) in GEN-injected rats. In NRK-52E cells, GEN increased the cellular ROS in the early treatment phase and ROS remained continuously high from 1.5 H to 24 H. Moreover, EG alleviated the increase of ROS and MDA and the decrease of GSH caused by GEN. Furthermore, EG activated the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). After the treatment of GEN, the protein level of cleaved-caspase-3, the flow cytometry analysis and the JC-1 staining, the protein levels of glutathione peroxidase 4 (GPX4) and SLC7A11, were greatly changed, indicating the occurrence of both apoptosis and ferroptosis, whereas EG can reduce these changes. However, when Nrf2 was knocked down by siRNA, the above protective effects of EG were weakened. In summary, EG attenuated GEN-induced nephrotoxicity by suppressing apoptosis and ferroptosis.


Objective: In the setting of acute ST-elevation myocardial infarction (STEMI), reperfusion therapy with primary percutaneous coronary intervention (PCI) performed by an experienced team or pharmacological reperfusion with thrombolytic therapy is highly recommended. Standard echocardiographic measurement of the left ventricular ejection fraction (LVEF) is widely used to assess left ventricular global systolic function. This study was designed to compare the assessment of global left ventricular function by standard LVEF and global longitudinal strain (GLS) in the two well-known reperfusion strategies. Materials and Methods: We conducted a retrospective single-center observational study in 50 patients with acute STEMI who underwent primary PCI (n = 25) and Tenecteplase (TNK)-based pharmacological reperfusion therapy (n = 25). The primary outcome was left ventricle (LV) systolic function after primary PCI, as assessed by two-dimensional (2D) GLS using speckle-tracking echocardiography (STE), as well as LVEF using standard 2D echocardiogram using Simpson's biplane method. Results: Overall mean age was 53.7 ± 6.9 years with 88% male gender. The mean door-to-needle time was 29.8 ± 4.2 min in the TNK-based pharmacological reperfusion therapy arm, and the mean door-to-balloon time was 72.9 ± 15.4 min in the primary PCI arm. LV systolic function was significantly better in the primary PCI arm as compared to the TNK-based pharmacological reperfusion therapy, both by 2D STE (mean GLS: −13.6 ± 1.4 vs. −10.3 ± 1.2, P ≤ 0.001) and LVEF (mean LVEF: 42.2 ± 2.9 vs. 39.9 ± 2.7, P = 0.006). There were no significant differences in mortality and inhospital complications in both groups. Conclusion: Global LV systolic function is significantly better after primary coronary angioplasty as compared to TNK-based pharmacological reperfusion therapy when assessed by routine LVEF and 2D GLS in the setting of acute STEMI.


The goal of the present dissertation is to improve the current state of the art in configuration management in networking experimentation infrastructures (testbeds). In particular, our goal is to solve the scenario technology-dependency problem, so the same scenarios can be reused in different testbeds. In order to achieve this goal, three objectives have to be addressed. First, to develop a modeldriven configuration management architecture that decouples scenario specifications from the testbeds in which they will be finally deployed. This has to be done without modifying existing testbeds or their management tools. Secondly, a Testbed Independent Model (TIM), based on DMTF's CIM, used as main architectural component in order to provide scenario technologyindependency. Finally, a generic and systematic methodology to transform TIM scenarios to the specification formats used in the different current or future testbeds. In order to achieve these objectives, our work includes an extensive analysis of the most salient experimentation infrastructures existing today, paying special attention to their configuration management systems. In addition, different technologies to model and transform management information are analyzed, in order to find the best one to base our architecture on. This dissertation also includes an experimental validation to assess the feasibility of our architecture, which is applied to two different testbeds used for real world experimentation. Additionally, several application cases are described, both for novel testbed architectures (such as the ones defined in Future Internet initiatives) and production environments.


Abstract Distribution network planning identifies the least cost network investment that satisfies load growth requirements without violating any system and operational constraints. Power injections from distributed generation change network power flows, modifying energy losses. Determining appropriate location and optimal size of distributed generation with respect to network configuration and load distribution in the feeder is main challenge in the changing regulatory and economic scenarios. Among the benefits of distributed generation is the reduction in active power losses, which can improve the system performance; reliability, and efficiency. In this article, the multi-location distributed generation placement problem aims to minimize the total active power loss of radial distribution networks using a genetic algorithm based solution algorithm. This technical benefit of energy savings due to the reduction in active power loss can also be translated into economic benefits. The loss sensitivity to the change in active power injection is used in selecting candidate location(s) for installation of distributed generation devices. A comparison of the results for loss reduction and savings with other reported methods show the effectiveness of the proposed method.


Introduction and objectives: Acute lymphoblastic leukemia (ALL) in pediatric patients is an issue that affects the quality of life of the patient and his family, so it is urgent to know the physiology, presentation, and functionality of the cell population that allows determining the more effective treatments. The objective is to review the evidence derived from cohort studies and clinical trials on ALL in pediatric patients. Method: A retrospective study carried out based on the search for cohort studies and clinical trials in the last 10 years in MEDLINE, EMBASE, and Cochrane Controlled Trials Register whose keywords [Acute and Lymphoblastic Leukemia], [epigenetical], [Drug Therapy], [Pediatric]. Results: 87 articles were found based on titles and abstracts, of which 16 focus on the age group and criteria of interest. Of the 10% of the known etiology, genetic alterations are more important. However, there are epigenetic modifications that are important for leukemia to occur, such as DNA methylation, histone modification, and regulation by non-coding RNAs. Discussion/conclusions: Acute lymphoblastic leukemia in a heterogeneous pathology and the study of its molecular biology is very useful to identify therapeutic targets and have greater effectiveness in treatment and increase disease-free survival with a longer-term than the current one. In each proposed treatment scheme, it is sought that there be greater effectiveness and less toxicity as in the AIEOP-BFM ALL or IDA-FLAG schemes.


The National Cancer Institute9s Minority-Based Community Clinical Oncology Program (MBCCOP), initiated in 1990, provides infrastructure support for the conduct of NCI-sponsored cancer control and symptom management, prevention and treatment trials in communities serving significant number of racial and ethnic minorities. As a component of a larger community oncology network, an additional goal of this program is to contribute to the understanding of and to the literature on cancer and health disparities in clinical research. The 13 currently funded MBCCOPs provide excellent examples of the challenges and successes of recruitment, enrollment and retention of clinical trials in public, community, academic and Veterans9 Administration environments. The objectives of this presentation are to (1) describe the impact of the MBCCOPs on the NCI clinical trials network; (2) discuss the lessons learned, with an emphasis on how the programs have met increasing challenges over nearly two decades; (3) provide examples of the different staffing needed for the conduct of clinical research for different institutions, (i.e., outreach vs. in-house data management, patient vs. nurse navigators; and (4) highlight how the MBCCOPs provide a resource for research across disciplines to help narrow cancer disparities. The John Stroger Hospital of Cook County will be highlighted to demonstrate how the cancer burden and the health status and needs at this public hospital led to trial selection, research projects and community engagement.


Abstract The aim of this paper is to provide an addendum to a paper by Rose with the same title which has appeared in an earlier issue of this Journal [2]. Our new result is: Theorem. A ring of characteristic zero which admits elimination of quantifiers in the language (0, 1, +, ·) is an algebraically closed field.


One of the future instruments to resolve the origin of the unidentified 3.5 keV emission line is the Micro-X sounding rocket telescope. According to the estimate made in 2015, Micro-X will be able to detect on average about 18.2 photons from the 3.5 keV line during its 300-second-long planned observation. However, this estimate is based on the extrapolation of the 3.5 keV line signal from the innermost Galactic Centre (GC) region available in 2015. With newly available reports on the 3.5 keV line emission in five off-centre regions, we found that similar Micro-X payload will result in 3.4-4.3 counts on average, depending on the dark matter distribution. Therefore, we show that the 3.5 keV line is unlikely to be detected with a single Micro-X launch using an original Micro-X payload. Increasing its field-of-view from 20$^\circ$ to 33$^\circ$ and its repointing out of GC (to avoid the brightest X-ray point source on the sky, Sco X-1) will increase the expected number of counts from 3.5 keV line to 7.5-7.9, which corresponds to its expected marginal ($\sim 2\sigma$) detection within a single Micro-X observation.


: The purpose of this article is to emphasize the nurse's role toward persons with arterial hypertension. Therefore it's introduced an application form that is used for nursing consultation to outpatients.


The new General Data Protection Regulation (GDPR) was approved on April 27 2016. The GDPR 2016/679 aims to ensure the coherence of natural persons' protection within the European Union (EU), comprising very important innovative rules that will be applied across the EU and will directly affect every Member State. Furthermore, it aims to overcome the existing fragmented regulations and to modernise the principles of privacy in the EU. This regulation will come into force in May 2018, bringing along several challenges for citizens, companies and other private and public organisations. The protection of personal data is a fundamental right. The GDPR considers a 'special category of personal data', which includes data regarding health, since this is sensitive data and is therefore subject to special conditions regarding treatment and access by third parties. This premise provides the focus of this research work, where the implementation of the GDPR in health clinics in Portugal is analysed. The results are discussed in light of the data collected in the survey and possible future works are identified.


There is a wealth of game theoretical approaches to the evolution and maintenance of cooperation between unrelated individuals and accumulating empirical tests of these models. This contrasts strongly with our lack of knowledge on proximate causes of cooperative behaviour. Marine cleaning mutualism has been used as a model system to address functional aspects of conflict resolution: client reef fish benefit from cleaning interactions through parasite removal, but cleaner fish Labroides dimidiatus prefer client mucus. Hence, feeding against their preference represents cooperative behaviour in cleaners. Cleaners regularly cheat non-predatory clients while they rarely cheat predatory clients. Here, we asked how precisely cleaners can adjust service quality from one interaction to the next. We found that non-predatory clients receive a better service if the previous client was a predator than if the previous client was a non-predator. In a related laboratory experiment, a handnet used as a stressor resulted in cleaners feeding more against their preference in subsequent interactions. The combination of the cleaners' behaviour in the two studies shows that the cleaners' service quality for a given client species is not fixed, but it can be manipulated. The results suggest that short-term stress is one factor that causes cleaners to increase their levels of cooperation, a hypothesis that is amenable to further experiments manipulating the endocrine system.


Purpose

This study aims to examine reciprocal exchange in teams using a psychological contract (PC) framework. Adopting Rousseau's conceptualization of the contract, the authors explore the extent to which the team members reciprocate perceived team obligations and fulfilment by adjusting their own obligations and fulfilment. A new scale for the measurement of obligations and fulfilment was developed. Team commitment was hypothesized as a mediating variable.

Design/methodology/approach

The new PC scale was tested in a longitudinal study design. A survey of a representative sample of 230 Dutch first-year college students nested in 73 teams was conducted.

Findings

The authors found that in student teams, perceived team obligations at Time 1 are positively associated with perceived member obligations at Time 2. Furthermore, they found higher commitment to the team as the team fulfilled the obligations as perceived by its members. Contrary to the exchange theory, in student teams, perceived fulfilment of obligations at Time 1 is not reciprocated by more obligations of its members at Time 2. No significant mediating effects are found of team commitment.

Originality/value

To date, this study provides the first measurement of contract fulfilment in non-hierarchical team relationships. The instrument can act as a tool to assess future team effectiveness and performance and adjust team composition accordingly.


This paper mainly dealt with the following problems by using a number-code substitution task: What kind of relation is there between reactive inhibition (IR) and reinforcement? Does reactive inhibition develop, whether reinforcement is given to subjects or not?Eight groups were so constructed that three variables (the intertrial rest, the rest inserted after twenty trials, and the verbal reinforcement) would be operated. The performance in 20 prerest trials and the reminiscence were compared between each group. The subjects in each group had 30sec practice in each trial.The following results were obtained:(1) The performance of the distributed-practice groups was superior to that of the massed-practice groups.(2) The group who had the intertrial rests of 1min was superior in the prerest performance to the group who had 15sec for each intertrial rest.(3) The performance of the 15-second rest group who was rewarded during each interval was not superior to that of the group who had 15sec for each intertrial rest with no reward.(4) The massed-practice group showed the statistically significant reminiscence.(5) The 15-second rest group showed the statistically significant reminiscence after the 10-min rest.(6) Whether reinforcement was given to the subjects or not, the reactive inhibition developed. This suggests that the reactive inhibition process is very similar to that of fatigue, though it is not clear whether this inhibition process is peripheral or central in the nervous system.


The observed seasonal and interannual fluctuations in the Brazil-Malvinas confluence region are investigated using a wind-driven isopycnic coordinate model of the South Atlantic Ocean south of 10°S. The model is configured on a rotated Mercator grid with 2° horizontal resolution and five constant-density layers in the vertical. In order to model the passage of the Antarctic Circumpolar Current (ACC) across the basin, the grid is augmented by a channel extension to the west of Drake Passage and east of 50°E, having the width of Drake Passage. A series of benchmark experiments with annual mean climatological forcing shows that (1) when bottom topography is included, one observes a reduction in Drake Passage transport in agreement with previous studies, as well as a northward shift in the Brazil Current separation latitude, (2) an increase in Drake Passage transport to realistic values does not cause any further northward shift in the separation point, and (3) the model is relatively insensitive to the choice of lateral boundary conditions. A second set of experiments, in which the forcing is by seasonal climatological wind data and the Drake Passage transport is relaxed to a constant annual mean value, indicates the presence of a semiannual signal in the annual transport cycles for the Malvinas Current and for the ACC through Drake Passage. That signal is significantly damped in the Brazil Current region, and the amplitude of each cycle is reduced in comparison to observations. When the value to which the Drake Passage transport is relaxed is allowed to vary in time, the semiannual wind-forced oscillation in the Malvinas region remains evident, with additional superimposed variations related to the variations in the transport forcing. The final experiments are forced by a 10-year data set of realistic wind stress values, providing 10-year time series of model output for analysis of the interrelationships of the principal Southwestern Atlantic currents. A high correlation at the semiannual period is found to exist among the cycles of Drake Passage transport, Malvinas Current transport, and seasonal movements of the Brazil-Malvinas confluence latitude, while the Brazil Current transport cycle exhibits a significant energy peak only at the annual period. We conclude that the locally wind-forced semiannual signal south of the confluence is significantly damped before reaching the Brazil Current region by several factors: friction, the opposing flow of the current itself, and the inability of the Malvinas to penetrate the subtropical circulation that is confined to the upper model layers.


This article reports an uncommon cause of gastrointestinal bleeding in a young male with uncorrected Tetralogy of Fallot (TOF). This is the first reported instance of gastrointestinal stromal tumor (GIST) causing bleeding in a patient with uncorrected TOF. A 32-year-old Caucasian male with severe developmental delay and uncorrected TOF presented with black tarry stools. On admission, the patient was hypotensive and tachycardic. He was successfully resuscitated with fluids and blood transfusion. Upper gastrointestinal endoscopy was performed and biopsy revealed GIST. It is interesting to note that the patient survived till this age without any medical or surgical treatment. This case presents GIST as a cause of gastrointestinal bleeding in uncorrected TOF. Cytogenetic analysis revealed deletion of short arm of chromosome 18. This case illustrates that tyrosine kinase inhibitor may be an acceptable alternative therapy to surgical resection.


Abstract : The NIST EXPRESS toolkit is a software library for building Express-related tools. This paper is one in a series describing the latest version of the toolkit. This document describes shortcomings of previous versions of the toolkit, requirements for improvement, and a recommended approach for addressing those requirements. A background knowledge of EXPRESS and the EXPRESS toolkit is presumed as well as a rudimentary grasp of basic compiler construction techniques.


In this study, settling experiment was performed about cohesive and sandy soils among representative sample expected to dredge and dump for analysis of settling and consolidation characteristic. The analysis showed the definite difference between cohesive soils and sandy soils of relationships with settling and consolidation coefficient, a water content, interfacial heights. But directly after a dredged reclamation, prediction results about a initial volume change showed that cohesive soil of a water content change was decreased rapidly as time goes by, but sandy soils made no difference in a water content change. Results were compared and analyzed with the settling and consolidation coefficient and a initial settling velocity by real soil amounts for a feasibility check about test conditions applied to these experiment: we judge that test conditions are appropriate, each material by such these analyses suggests the scope of settling and consolidation coefficient, average and the representative relational formula.


OBJECTIVE
To explore the value of the POSSUM scoring system in predicting postoperative morbidity and mortality of pancreatoduodenectomy (PD).

METHODS
Two hundreds and sixty-five consecutive PDs were performed between January 2005 and December 2007. POSSUM scores which relied on 12 physiologic and 6 operative variables were prospectively calculated for each case. Expected morbidity and mortality were estimated based on POSSUM scores and were compared with observed morbidity, which were diagnosed according to the Clavien complication scheme and domestic reference criteria respectively, and mortality.

RESULTS
Physiologic scores of 265 cases ranged from 12 to 24,the mean was 15. Operative scores ranged from 14 to 24, the mean was 17. The overall POSSUM scores ranged from 0.24 to 0.88. Average expected morbidity was 43.8%, expected cases were 116. Observed morbidity rate was 39.6% (105/265). The expected and observed morbidities and cases had no significantly differences. All patients were classified to 1 of 4 strata based on their individual POSSUM scores and subsequent risk of morbidity. Predictive value was the highest when scores ranged from 0.4 to 0.8. POSSUM exhibited less predictive value for mortality, but if POSSUM was more than 0.5, it was useful for mortality predicting.

CONCLUSIONS
POSSUM scoring system has high value for predicting the risk of morbidity in PD and can be helpful in guiding surgery and postoperative management decisions.


OBJECT
The authors prospectively assessed the value of awake craniotomy used nonselectively in patients undergoing resection of supratentorial tumors.

METHODS
The demographic features, presenting symptoms, tumor location, histological diagnosis, outcomes, and complications were documented for 610 patients who underwent awake craniotomy for supratentorial tumor resection. Intraoperative brain mapping was used in 511 cases (83.8%). Mapping identified eloquent cortex in 115 patients (22.5%) and no eloquent cortex in 396 patients (77.5%).

RESULTS
Neurological deficits occurred in 89 patients (14.6%). In the subset of 511 patients in whom brain mapping was performed, 78 (15.3%) experienced postoperative neurological worsening. This phenomenon was more common in patients with preoperative neurological deficits or in those individuals in whom mapping successfully identified eloquent tissue. Twenty-five (4.9%) of the 511 patients suffered intraoperative seizures, and two of these individuals required intubation and induction of general anesthesia after generalized seizures occurred. Four (0.7%) of the 610 patients developed wound complications. Postoperative hematomas developed in seven patients (1.1%), four of whom urgently required a repeated craniotomy to allow evacuation of the clot. Two patients (0.3%) required readmission to the hospital soon after being discharged. There were three deaths (0.5%).

CONCLUSIONS
Awake craniotomy is safe, practical, and effective during resection of supratentorial lesions of diverse pathological range and location. It allows for intraoperative brain mapping that helps identify and protect functional cortex. It also avoids the complications inherent in the induction of general anesthesia. Awake craniotomy provides an excellent alternative to surgery of supratentorial brain lesions in patients in whom general anesthesia has been induced.


In early 2018, Google announced Kotlin to be one of the official languages for developing Android applications (next to Java). Moreover, several studies reveal that Kotlin is about to make its way to an important language in the developer community. Developers praise the conciseness, short syntax and null pointer safety. No question, a competition has started, but can Kotlin replace Java in the long run? Several factors (combined) will determine if a developer decides learning and/or using Kotlin over Java. Of course, it is also a question of investment. Furthermore, one of the major questions is: Does the short syntax and conciseness of Kotlin causes less occurrences of bad practices? In order to shed light on this question, an experiment was conducted. Java and Kotlin repositories were downloaded from GitHub, bad practices in the respective projects were analysed, counted, summed up and eventually saved in CSV files. After that, several well established statistical methods were applied to the data to get meaningful results. The main conclusion is: A substantial difference in the occurrence of bad practices can not be confirmed.


In view of India unlocking, to secure a large population of this country, the healthcare facilities delivering primary care as well standalone health facilities need to be secured from impacts of COVID-19 pandemic. This document dwells on the broader guidelines for primary care practitioners/standalone private health facilities/frontline healthcare facilities to mitigate the impact of COVID-19 Pandemic. The authors understand that the situation is evolving, so the guidelines too will keep evolving.


The computational efficiency of the FEA is strongly dependent on the algorithmic and numerical efficiency of the FE solver. This is particularly important in case of implicit FE codes, such as DD3IMP, the in‐house static implicit FE solver under analysis in this work. This study describes the procedure adopted to identify the main computational bottlenecks of the FE solver in order to introduce the OpenMP directives and, consequently, to achieve a major speedup of the whole algorithm. The different parallelized branches of the code are tested using the well‐known square cup deep drawing example, considering different FE discretizations. The analysis of the preliminary results, concerning the CPU wall time, allows to demonstrate that the adoption of HPC techniques, such as the abovementioned OpenMP directives, enables to: (i) achieve a speedup factor close to the number of cores (in a single computer); (ii) solve a problem in a shorter time; (iii) solve a bigger problem in the same amount of time and, thus, (iv) achieve a better solution in a given amount of time.


In this work we study whether parametrized spherically symmetric black hole solutions in metric theories of gravity can appear to be isospectral when studying perturbations. From a theory agnostic point of view, the test scalar field wave equation is the ideal starting point to approach the quasi-normal mode spectrum in alternative black hole solutions. We use a parametrization for the metric proposed by Rezzolla and Zhidenko, as well as the the higher order WKB method in the determination of the quasi-normal mode spectra. We look for possible degeneracies in a tractable subset of the parameter space with respect to the Schwarzschild quasi-normal modes. Considering the frequencies and damping times of the expected observationally most relevant quasi-normal modes, we find such degeneracies. We explicitly demonstrate that the leading Schwarzschild quasi-normal modes can be approximated by alternative black hole solutions when their mass is treated as free parameter. In practice, we conclude that the mass has to be known with extremely high precision in order to restrict the leading terms in the metric expansion to currently known limits coming from the PPN expansion. Possible limitations of using the quasi-normal mode ringdown to investigate black hole space-times are being discussed.


Quantitation of HBV-DNA is the most precise test for measuring viral replication. A commercial liquid phase hybridation test (Abbott) is now commonly used for diagnosis and monitoring of chronic hepatitis B. Interpretation of weak positive results obtained with this test are often difficult. Fifty-four sera with a concentration lower than 12 pg/ml with the Abbott HBV-DNA assay were tested with another commercial hybridation assay (Digene-Murex) and with an in-house PCR test. PCR is positive in 24 sera among the 35 HBs antigen positive sera, but is always negative in HBs Antigene negative sera. All the HBe Antigen positive sera were positive with the PCR test. A positive result was obtained with the Digene test in only 14 sera, 13 of them were confirmed by PCR. Ten sera among the remaining 11 PCR positive sera had a low HBV-DNA concentration but under the Digene cut-off level (10 pg/ml). The sensitivity could be greatly enforced with a lower cut-off level without any lack of specificity. The PCR test remains very helpful for sera with low concentration of HBV-DNA.


Maslahah in al-Juwayni's thinking is not a source of law, but it is an indicator in determining the existence of a law. Basically, maslahah which is the basis and purpose of the establishment of sharia, in the view of al-Juwayni, concerns all universal human needs that can guarantee the maintenance and uphold of human life's milestones. This is al-Juwayni's formulation includes four things, namely guaranteed the maintenance of religion, soul, honor (ancestry), and human property. Then in making istinbat a law, especially related to cases that have not been regulated by the legal status, it must refer to the five categories of maslahah as formulated by al-Juwayni. These five categories are the basis and purpose of the making and determination of the law found in the text.


The aim of this qualitative study was to investigate existing knowledge and the use of communication strategies in emotional care for patients receiving palliative care in Brazil. It was performed from August, 2008, to July, 2009, with 303 health professionals who worked or had frequent contact with patients receiving palliative care, using a questionnaire. Data was submitted to descriptive and analytical statistical treatment. The professionals reported not knowing about communication strategies, showing a significant difference (p-value 0.0011) in comparing subjects with and without previous training in palliative care, showing that those who had received proper training know/use more communication strategies when providing care for their patients on an emotional level. The strategies most often cited were: careful listening, verbal reaffirmation of care, using open questions, and affective touch. We conclude that there is little knowledge and poor use of communication strategies among health professionals in towards the emotional care of patients receiving palliative care.


The left ventricular assist device (LVAD), used thus far as a bridge to heart transplantation, may offer an alternative to heart transplantation. Because patients receiving LVADs are in cardiogenic shock, many experience acute ischemic renal failure in the peri-implantation period. We describe 10 patients who underwent dialysis after receiving LVADs for end-stage heart disease. Among 37 patients who received an LVAD, 10 required dialytic support (8 men, 2 women; mean age, 47.3 ± 11.3 yr; mean APACHE II score at ICU admission, 18.0 ± 4.7). Renal replacement therapy was started for fluid removal within 48 hours of LVAD implantation in 8 patients. Continuous renal replacement therapy (CRRT) was the first-line modality for 9 patients, including 3 slow continuous ultrafiltrations (SCUF), 4 continuous venovenous hemofiltrations (CWH), 5 continuous venovenous hemodiafiltrations (CWHD), 2 continuous arteriovenous hemofiltrations (CAVH), and 1 continuous arteriovenous hemodiafiltration (CAVHD). Patients remained on CRRT for a mean of 14.4 ± 6.1 days, and 5 were eventually changed to intermittent hemodialysis. The mean time on renal replacement therapy was 27.8 ± 19.7 days. During CRRT, despite daily average ultrafiltration of 3,445 ± 623 mL, net fluid loss was only 358 ± 507 mL/day. Metabolic control achieved with CRRT, expressed as mean ± SD, was: BUN 75.5 ± 13.0 mg/dL (26.9 ± mmol/L), serum creatinine 4.0 ± 0.7 mg/dL (354 ± 62 mmol/L), carbon dioxide content (bicarbonate plus dissolved CO2) 21.5 ± 1.7 mEq/L, and serum electrolytes within normal limits. Survival for patients with LVADs who did not require dialysis was 93% compared with 40% for the group with combined LVADs and dialytic support. The 4 patients who survived in the dialysis group all recovered renal function, and their need for dialysis ceased within 18 to 33 days. Mean serum creatinine levels at follow-up after transplantation were 2.0 ± 1.0 mg/dL (177 ± 88 mmol/L). In conclusion, CRRT provides good metabolic control and allows large ultrafiltration volume in patients supported by an implantable LVAD. We observed a 40% survival rate in patients with combined LVADS and dialytic support, and the survivors all recovered renal function.


In this study, we evaluate and compare two different approaches for multilingual phone recognition in code-switched and non-code-switched scenarios. First approach is a front-end Language Identification (LID)-switched to a monolingual phone recognizer (LID-Mono), trained individually on each of the languages present in multilingual dataset. In the second approach, a
 common multilingual phone-set
 derived from the International Phonetic Alphabet (IPA) transcription of the multilingual dataset is used to develop a Multilingual Phone Recognition System (Multi-PRS). The bilingual code-switching experiments are conducted using Kannada and Urdu languages. In the first approach, LID is performed using the state-of-the-art i-vectors. Both monolingual and multilingual phone recognition systems are trained using Deep Neural Networks. The performance of LID-Mono and Multi-PRS approaches are compared and analysed in detail. It is found that the performance of Multi-PRS approach is superior compared to more conventional LID-Mono approach in both code-switched and non-code-switched scenarios. For code-switched speech, the effect of length of segments (that are used to perform LID) on the performance of LID-Mono system is studied by varying the window size from 500 ms to 5.0 s, and full utterance. The LID-Mono approach heavily depends on the accuracy of the LID system and the LID errors cannot be recovered. But, the Multi-PRS system by virtue of not having to do a front-end LID switching and designed based on the
 common multilingual phone-set
 derived from several languages, is not constrained by the accuracy of the LID system, and hence performs effectively on code-switched and non-code-switched speech, offering low Phone Error Rates than the LID-Mono system.


The study was conducted at University of Gujrat during 2015 with an objective to explore the effects of dust on Free Space Optics (FSO) communication. Growing pollution and dust gales motivated studies we presented in this paper. In this paper analysis of the influence of dust on free space optics communication is presented. We focused our studies on Lahore as it is polluted city of Punjab and made a comparison with dust effects in Rahimyar Khan Region. Dense dust consists of large dust particles that raise from Earths sphere and whose atmospheric intensification values are high enough to affect FSO communication links. Dust storm research is based on visibility data. In order to test visibility data, we made calculations of atmospheric conditions for different dust conditions. Visibility of wave is calculated using weather spark. As it is related with the optical attenuation, so we also calculated optical attenuation of dust particles due to influence of dust particles and compared it with that of Rahimyar Khan.


The 1994 Rwandan Genocide continues to have serious repercussions for peace and stability in the Great Lakes region of Africa. Here, the contributors look at the continuation of the conflict in the territory of Zaire, ultimately asking how best to handle a problem which has been a source of instability for years - the problem of refugee warriors.


Abstract This article examines the work of Robert Hurd (1905–1963), a Scottish nationalist architect, planner, and admirer of Scottish civic traditions, in order to query and enrich current anthropological approaches to "material politics" with their focus on material assemblies, infrastructures, and interactions that operate across scales and beyond discourse. Hurd was both an expert and planner and also an "artisan of nationalism" who sought to restore Scotland's built environment as at once a civic heritage and a material resource for a future of independence and self-determination. Hurd's attention to distinctively Scottish architectural forms and to historic centers and their development over time is significant as an idiom of nationalist thought, while his architectural work highlights the formal manipulation of scale and centrality to express political aspirations. He was an expert not only of infrastructure, plans, or populations and their needs, but also of the mediation of such material facts into architectural form and, in a broader sense, forms of life. Finally, Hurd's writing on "burgh" civic and architectural traditions, and his work as a conservation architect, together allow a better understanding of the role played by a conservative, tradition-minded modernism, and of narratives of tradition and national evolution, in the twentieth-century history and present development of Scotland's national and constitutional politics.


Candida albicans was cultured from the upper gastrointestinal tract of 44% and from the lower alimentary tract in 6% of 50 common pigeons (Columba livia). Thirty per cent of the samples of pigeon droppings collected from different locations were positive for the yeast. The colony forming units for positive samples ranged from 2 × 102-2·8 × 106 per g dry feces. The percentage of antigenic Groups A and B for the strains of C. albicans isolated was approximately the same as for strains isolated from human sources.


Vocabulary is one of the three essential components that constitute language knowledge, and vocabulary teaching is an essential part in English language teaching. In this paper, we discuss some vocabulary teaching strategies, so as to help the memorizing of vocabulary and enhance the efficiency of vocabulary teaching and learning.


Torra J, Cirujeda A, Recasens J, Taberner A & Powles SB (2010). PIM (Poppy Integrated Management): a bio-economic decision support model for the management of Papaver rhoeas in rain-fed cropping systems. Weed Research50, 127–139.

Summary

A bio-economic model for Papaver rhoeas designed for dry-land cropping systems in Spain was developed. The model included four seed bank layers to simulate seed movement in the soil profile resulting from tillage, with different emergence rates and seed bank mortalities depending on soil cultivation and burial depth. Users of Poppy Integrated Management (PIM) might specify the crop sequence and any feasible combination of 38 different weed management practices (herbicide and non-herbicide options) each year over 10 or 20 years. Weed treatment options included selective herbicides (14), non-selective herbicides (1), non-herbicide treatments (11) and user-defined treatments (1). PIM represented weed and seed bank population dynamics, weed–crop competition, weed treatment impacts, agronomic practices and financial details. The bio-economic model could be used to evaluate weed management scenarios by investigating the implications of different tillage, fallow and cereal rotational sequences and of constraints on herbicide availability. Model validation combined available data from literature with our own data, to show that PIM was sufficiently accurate for predicting P. rhoeas population dynamics. Sensitivity analyses indicated that economics associated with fuel, fertiliser and seed costs, as well as grain yield and price, were primary drivers of management decisions, whereas seedling emergence and initial seed bank size were of secondary importance.


My thesis is an exploration of the architectural production surrounding the French philosopher Gilles Deleuze, specifically, through the overarching theme of Deleuze's theory of subjectivity, which I will call subjectivization. I interpret this to mean the strange coalescence of matter, architectural subject, and event, in architectural experience and culture. I speculate that subjectivization presents a yet under-explored dimension of deleuzianism in architecture. In order to develop this I pursue two independent trajectories: firstly the narrative of architectural production surrounding Deleuze, from the 1970s until today, as it is an emergence of changing groupings, alliances, formations and disbandment in the pursuit of creative-intellectual tasks—what might be called the subjectivization of architecture—and, secondly, through a speculation about the architecture of subjectivization—that is, an attempt to explore, concretely, what might be the space and time of subjectivization.

Chapter One traces an oral history of deleuzianism in architecture, through conversations with Sanford Kwinter and John Rajchman, describing how the Deleuze milieu makes its way into architectural practice and discussion—subjectivization as a social and cultural emergence—whereas Chapter Two theorizes the emergence of an architectural subjectivity where architecture constitutes its own affective event—what I call subjectivization or material becoming-subject.


Together with determining the bone age of the immature and/or small-for date neonate, it is possible to work out the length of the tibia on the profile X ray of the leg. Authors have drafted up a scale of growth, featuring the 10 th, 50 th and 90 th percentiles common for boys and girls ranging from 28 to 42 weeks of gestation and they propose this new criterion for the study of pathological neonates, particularly the small-for-date. The method has a second advantage: it is possible to follow the increment of the tibia length by X rays taken at regular intervals and thus to estimate the various factors that can interfere with the child's growth, and in the first place, the quality of the food given to the child.


The decay $\tau^{-}\to K^{-}K_S\nu_{\tau}$ has been studied using $430\times10^6$ $e^+e^-\to \tau^+\tau^-$ events produced at a center-of-mass energy around 10.6 GeV at the PEP-II collider and studied with the BABAR detector. The mass spectrum of the $K^{-}K_S$ system has been measured and the spectral function has been obtained. The measured branching fraction ${\cal B}(\tau^{-}\to K^{-}K_S\nu_{\tau}) = (0.739\pm 0.011(\rm stat.)\pm 0.020(\rm syst.))\times 10^{-3}$ is found to be in agreement with earlier measurements.


The session initiation protocol (SIP) is the IETF alternative for session related signalling. SIP was used in the IP multimedia subsystem of 3rd generation partnership project (3GPP) UMTS networks. To be able to guarantee quality of service (QoS) to customers in carrier grade networks it is required to ensure QoS for signalling. Resources provided by the multiservices transport network have to be allocated to the signalling traffic. This paper introduces a methodology that enables dynamic resource allocation (DRA) on the basis of current message numbers. In particular, it can be used to dimension virtual SIP links (VSLs). The paper defines the DRA scheme, outlines its operation and gives simulation results that underline the advantages of dynamic resource allocation.


Multi-path transport is an important mechanism for supporting video communications in multihop wireless networks. In this paper, we investigate the joint problem of optimal path selection and rate allocation for multiple video sessions in a wireless mesh network. We present a mathematical formulation to optimize the application level performance (i.e., video distortion) in the context of path selection and rate allocation. For this complex optimization problem, we propose a branch-and-bound based solution procedure, embedded with the reformulation-linearization technique (RLT) that can produce (1-epsiv)-optimal solutions for any small epsiv . This result is significant as it not only provides theoretical understanding of this problem, but also offers a performance benchmark for any future proposed distributed algorithm and protocol for this problem. Simulation results are also provided to demonstrate the efficacy of the solution procedure.


Peritoneal mesothelioma was diagnosed in a 54-year-old female, who had never been exposed to asbestos. The clinical picture was dominated by progressive abdominal distension due to the development of ascites as well as tumor, severe right hypochondralgia and intermittent fever. Abnormal laboratory findings ESR, CRP, mild leukocytosis with normal differential, high serum levels of ferritin and /32-microglobulin, and an abnormal accumulation of isotope in the right upper quadrant of the abdomen on Ga scintigram. On exploratory laparotomy, the liver was found to be surrounded by tumor tissue, but histological examination was not diagnostic. A saliva test of the tissue was positive, indicating a high glycogen content. At autopsy the tumor was found to consist of two elements, epithelial and sarcomatoid. The final diagnosis was peritoneal mesothelioma.


Fish larvae of 'corvinas' (Pachyurus bonariensis and Plagioscion ternetzi) from Sinhá Mariana Lagoon, Mato Grosso State, were collected from March 2000 to March 2004, in order to determine the parasitic fauna of fishes. Larvae from the two species were parasitized by the same endoparasites: Contracaecum sp. Type 2 (larvae) (Nematoda: Anisakidae) in the mesentery and Neoechinorhynchus (Neoechinorhynchus) paraguayensis (Acanthocephala: Neoechinorhynchidae) in the stomach and the terminal portion of the intestine. Statistical analysis showed that there was a significant positive correlation between the standard length of hosts and the abundance of acanthocephalans and nematodes, and that the prevalence of nematodes presented a significant positive correlation with the standard length of the two species of hosts, indicating the presence of a cumulative process of infection. The present study constitutes the first record of nematodes and acanthocephalans parasitizing larval fish, as well as the first record of endoparasites in fish larvae in Brazil. In addition, it lists a new locality and two species of hosts for Contracaecum sp. Type 2 (larva) and N. (N.) paraguayensis.


Sustainability and environmental impact are important factors to consider in the software industry and especially in the training of the professionals who produce it. The non-renewable and increasingly limited resources of our planet generate the need to train engineers in the software area to assume their responsibility for sustainable development. Progress should be made in the inclusion of sustainable development principles in the curricula in the training of future software engineers. This article presents an analysis and monitoring of scientific publications, using bibliometric indicators in order to obtain and provide information on current research trends in the training of professionals in the area of software engineering with principles of sustainable development. For this reason, we conducted a bibliometric study of the Scopus database over the last 10 years, between 2010 and 2019, focusing on keywords such as software, education, teaching, learning, sustainable development and their respective variations. A systematic review method was used in this work, which produced an initial result of 581 papers. Subsequently, it was filtered through the thematic area of Computer Science, obtaining 232 documents. Subsequently, it was filtered by the Sustainable Development and education keywords, additionally filtering by documents type articles and conference publications for a result of 186 documents that resulted in 116 publications with at least one citation and 70 publications with zero citations. The analysis was performed using the search results analysis tool provided by Scopus and, in addition, VOSViewer as a tool to build and visualize bibliometric networks. The differential contribution of this study lies in the filtering, organization and analysis of 186 publications that allows it to be a source of bibliometric information that is expected to be an instrument that helps to focus future research in the area of sustainable software development. Overall and in accordance with the bibliometric indicators taken into account in this work, it is generally concluded that the Latin American region has very low impact production in the study area, than the areas of software engineering with the highest volume of Research related to sustainable development are requirements engineering, software design and architecture.


We classify noncompact homogeneous spaces which are Einstein and asymptotically harmonic. This completes the classification of Riemannian harmonic spaces in the homogeneous case: Any simply connected homogeneous harmonic space is flat, or rank-one symmetric, or a nonsymmetric Damek-Ricci space. Independently, Y. Nikolayevsky has obtained the latter classification under the additional assumption of nonpositive sectional curvatures [Ni2].


The formulae decoctions are commonly used in clinic and have characteristics of simple preparation and rapid effect. It was considered as a complex physical and chemical system. In this article, the physical and chemical properties and chemical components and their relationships were investigated to explore the changes of characteristics resulted from different combinations of drugs of Shaofu Zhuyu decoction. The method of partial leasts-quares regression was adopted to evaluate the correlation between physical and chemical parameters and chemical components. These researches may provide a new way to investigate the state of bioactive components, the action mechanisms, and property of treating diseases of traditional Chinese medicine decoction.


teaching learning practices how Dr. Finelli's research interests include student resistance to active learning, faculty adoption of evidence-based teaching practices, the use of technology and innovative pedagogies on student learning and success, and the impact of a flexible classroom space on faculty teaching and student learning. She also led a project to develop a taxonomy for the field of engineering education research, and she was part of a team that studied ethical decision-making in engineering students.


THE SUSTAINABILITY OF FINANCIAL FLOWS to developing countries depends heavily on the health of the corporate sector, which has been at the center of several recent crises. Corporate borrowers now account for more than a fifth of cross-border debt flows, compared with less than 5 percent in 1990, and flows of FDI, the dominant form of external financing for developing countries, are ultimately tied to corporate performance. Despite efforts to pay down debt since the 1997–98 crisis and the broad shift to flexible exchange rates, the corporate sector in developing countries remains subject to considerable risk. Corporate profitability in developing countries has shown a significant decline in recent years. As is painfully evident from the Asian crisis of 1997–98 and the more recent global high-tech collapse, capital flows that do not produce adequate returns are liable to sudden reversal. Many Asian corporations remain highly leveraged, in part because they substituted domestic for external debt. Those debt loads are more manageable now than they were in 1997–98, however, because interest rates are lower and creditors are more willing to roll over credits. Companies in Latin America and Eastern Europe, also highly leveraged, have increased their dependence on foreign finance. Dependence on foreign borrowing brings both risks and benefits. An excessive dependence on external finance hurt many Asian corporations in 1997–98. On the other hand, firms (especially Latin American firms) active in international markets during the 1990s appear to have benefited from a lower cost of capital. There is a need to improve the quality and timeliness of corporate data in developing countries.


Abstract Objectives. The aim of this study was to present up to date information concerning the diagnosis and treatment of primary aldosteronism (PA). PA is the most common cause of endocrine hypertension. It has been reported up to 24% of selective referred hypertensive patients. Methods. We did a search in Pub-Med and Google Scholar using the terms: PA, hyperaldosteronism, idiopathic adrenal hyperplasia, diagnosis of PA, mineralocorticoid receptor antagonists, adrenalectomy, and surgery. We also did cross-referencing search with the above terms. We had divided our study into five sections: Introduction, Diagnosis, Genetics, Treatment, and Conclusions. We present our results in a question and answer fashion in order to make reading more interesting. Results. PA should be searched in all high-risk populations. The gold standard for diagnosis PA is the plasma aldosterone/plasma renin ratio (ARR). If this test is positive, then we proceed with one of the four confirmatory tests. If positive, then we proceed with a localizing technique like adrenal vein sampling (AVS) and CT scan. If the lesion is unilateral, after proper preoperative preparation, we proceed, in adrenalectomy. If the lesion is bilateral or the patient refuses or is not fit for surgery, we treat them with mineralocorticoid receptor antagonists, usually spironolactone. Conclusions. Primary aldosteronism is the most common and a treatable case of secondary hypertension. Only patients with unilateral adrenal diseases are eligible for surgery, while patients with bilateral and non-surgically correctable PA are usually treated by mineralocorticoid receptor antagonist (MRA). Thus, the distinction between unilateral and bilateral aldosterone hypersecretion is crucial.


AbstractIn this paper, the authors have studied the effects of the different sintering atmospheres (vacuum, nitrogen-hydrogen, and dissociate ammonia) on 50A-50F duplex stainless steels, fabricated by the powder metallurgy process.The DSS sintered in atmosphere of N2-H2 exhibit a tensile strength of at least 500 MPa with an elongation to fracture smaller than 2%. The presence of nitrides was the main cause of the deterioration in the corrosion resistance.


This paper examines the changes in the size distribution of firms in the abortion services market between 1978 and 1992 in the US. The results indicate that for the entire 15-year period, the market shares of large abortion providers were increasing in both restrictive and nonrestrictive states. Also clinics and physician offices appear to be gaining market share relative to hospitals. These increasing market shares could be due to many factors, such as changes in the technology of providing abortions on an outpatient basis and changes in the relative prices of abortions in hospitals and abortions in non-hospital settings. Furthermore, this paper includes an analysis of the impact of state-level Medicaid funding regulations on the number, size, and type of abortion provider. These results have important implications for women's access to abortion services and for infant and maternal health.


Bruton9s tyrosine kinase (Btk) is an essential component of the B-cell receptor (BCR) signaling pathways regulating survival, activation, proliferation, and differentiation of B lymphocytes. The first Btk inhibitor, Ibrutinib, has demonstrated a significant clinical efficacy in a variety of B-cell malignancies. Through structure-guided approach, we have discovered two series of novel and potent Btk inhibitors, represented by EBI-1266 and EBI-1367, respectively. Both of these compounds showed high potency in inhibiting Btk kinase activity and growth of a number of aggressive lymphoma cell lines driven by aberrant BCR signaling, with IC50 value within low nanomolar range. Mechanistic studies examining BCR signaling pathway in related B cell lymphoma cell lines revealed that both EBI-1266 and EBI-1367 potently inhibited Btk phosphorylation and downstream Erk phosphorylation, similar to Ibrutinib. Furthermore, each compound showed unique and significant superiority over Ibrutinib: EBI-1266 had a cleaner selectivity profile against a panel of kinases with a cysteine residue in the conserved catalytic domain, and EBI-1367 exhibited >10-fold higher in vivo exposure in multiple preclinical species. In a tumor xenograft mouse model where tumor growth is dependent on Btk activity, both EBI-1266 and EBI-1367 showed significant oral anti-tumor activities, with EBI-1367 being more efficacious than Ibrutinib, consistent with a higher exposure of EBI-1367 in both blood and tumor tissues. No evidence of overt toxicities was observed in rodents with prolonged oral administration for two weeks with doses at least 3-fold above a highly efficacious dose. In summary, the pharmacological profiles of EBI-1266 and EBI-1367 indicate that these compounds have a great potential to become the next generation of Btk inhibitors, offering advantages in pharmaceutical development, enhanced in vivo efficacy and reduced toxicities. We are currently performing IND-enabling studies aiming to initiate phase I clinical trials for these Btk inhibitors. Citation Format: Jiayin Zhang, Dong Liu, Ru Shen, Yinfa Yan, Liuqing Yang, Minsheng Zhang, Jun Feng, Beibei Fu, Jerry Hu, Biao Lu, Hong Wan, Lei Zhang, Weikang Tao, Lianshan Zhang, Jingsong Cao. Discovery and pharmacological characterization of the second generation of Btk inhibitors with improved target selectivity and enhanced in vivo efficacy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2599. doi:10.1158/1538-7445.AM2015-2599


The elastic wavefields generated by surface loads in a transversely isotropic (TI) half-space of general orientation are studied. First, we consider the field of a point source, that is, Green's tensor of Lamb's problem for a TI solid. The complete far-field asymptotics of a quasi-longitudinal (qP) and two quasi-shear (qSH and qSV) waves are derived, including irregular directions. Then we present new computationally efficient high-frequency asymptotic models of the wavefields radiated by rectangular and circular transducers into a TI half-space.