. In the range of 1200°C to 1500°C, the transient hot-wire method was applied to measure the thermoconductivity of boron-containing slag, and the characteristics relationship of thermoconductivity with temperature was obtained. The thermoconductivity decreased rapidly with the elevation of temperature in the concerned temperature zone. The effect of thermoconductivity from compositions was obtained in the concerned temperature zone. The thermoconductivity increased with the increase of component of SiO2 and MgO. This is in favor of realization of quick cooling and increasing efficiencies of extraction of boron. This study not only provides an important properties parameter for the integrated utilization of boron-containing slag and helps to understand the conductivity mechanism of boron-containing slag, but also has a reference significance and practical value about the development of heat conduction theory in silicate system.


Abstract The internal architecture and external form of fluvial channel bodies is governed by both intrinsic and extrinsic controls. Extrinsic controls such as climate, eustasy, and tectonism are believed to have modest effects on channel-body types and geometries in high-subsidence settings. The effects of climate are particularly cryptic in high-accommodation settings and have proven extremely difficult to separate from other extrinsic controls such as tectonics and eustasy. The thick successions preserved in such basins have the potential to be relatively stratigraphically complete and are, therefore, valuable for interpreting basin evolution. This study documents the external geometry and internal architectural styles of fluvial channel bodies in a spectacularly exposed, 7-km-thick, Mississippian–Permian section from the Cumberland Basin, Atlantic Canada. Four fluvial styles are recognized: perennial, strongly seasonal, ephemeral, and fixed. Fluvial styles are not randomly distributed throughout the stratigraphic succession; instead discrete stratigraphic intervals consist of predominantly one type of fluvial style. Four stratigraphic intervals (E1–E4) in which strongly seasonal fluvial styles are predominant are recognized and alternate with intervals that are characterized by either perennial or ephemeral deposits. This suggests that a coherent record of climate change as manifested by changes in precipitation and runoff regime is recorded in the internal architecture of sandbodies.


Abstract Human epidermal growth factor receptor type 2 (HER2) is overexpressed in various cancers; thus, HER2-targeting single-domain antibodies (sdAb) could offer a useful platform for radioimmunotherapy. In this study, we optimized the labeling of an anti-HER2-sdAb with the α-particle-emitter 225Ac through a DOTA-derivative. The formed radioconjugate was tested for binding affinity, specificity and internalization properties, whereas cytotoxicity was evaluated by clonogenic and DNA double-strand-breaks assays. Biodistribution studies were performed in mice bearing subcutaneous HER2pos tumors to estimate absorbed doses delivered to organs and tissues. Therapeutic efficacy and potential toxicity were assessed in HER2pos intraperitoneal ovarian cancer model and in healthy C57Bl/6 mice. [225Ac]Ac-DOTA-2Rs15d exhibited specific cell uptake and cell-killing capacity in HER2pos cells (EC50 = 3.9 ± 1.1 kBq/mL). Uptake in HER2pos lesions peaked at 3 hours (9.64 ± 1.69% IA/g), with very low accumulation in other organs (<1% IA/g) except for kidneys (11.69 ± 1.10% IA/g). α-camera imaging presented homogeneous uptake of radioactivity in tumors, although heterogeneous in kidneys, with a higher signal density in cortex versus medulla. In mice with HER2pos disseminated tumors, repeated administration of [225Ac]Ac-DOTA-2Rs15d significantly prolonged survival (143 days) compared to control groups (56 and 61 days) and to the group treated with HER2-targeting mAb trastuzumab (100 days). Histopathologic evaluation revealed signs of kidney toxicity after repeated administration of [225Ac]Ac-DOTA-2Rs15d. [225Ac]Ac-DOTA-2Rs15d efficiently targeted HER2pos cells and was effective in treatment of intraperitoneal disseminated tumors, both alone and as an add-on combination with trastuzumab, albeit with substantial signs of inflammation in kidneys. This study warrants further development of [225Ac]Ac-DOTA-2Rs15d.


Purpose. This work provides information about households where grandparents assume roles as full‐time surrogate parents to their grandchildren. Social policy implications of these relationships and potential social policy changes to help these families are presented. Methodology. A comprehensive review of the literature was conducted to appropriately represent the phenomenon of grandparents raising grandchildren. Information regarding the functioning of both grandparents and grandchildren are addressed. Findings. Grandparents who raise their grandchildren tend to experience elevated levels of stress that negatively impact their social, emotion, and physical well‐being. Children in these families may encounter problems with psychological development, adjustment, and educational functioning. Grandparents who raise their grandchildren significantly influence the development of these children in the social and educational environments. The children also impact their grandparents' well‐being. The findings underscore the need to consider social policy implications for these families. Originality/Value. This work emphasises the functioning of not only grandparents in these families, but grandchildren as well. Additionally, information is provided regarding the pejorative impact of certain social policies on grandparents' social‐emotional well‐being and the grandchildren's behavioural and educational functioning. Social policy propositions are offered to help these families. The information in this article will likely help professionals in governmental, social service, and educational agencies work better with these families.


This paper describes a simulation study of reconnection options for white sturgeon Acipenser transmontanus subpopulations in adjacent river segments above and below CJ Strike Dam on the Snake River, Idaho, USA. In contrast to the downstream river segment, the upstream river segment is long and has areas that are suitable for spawning during normal and wet hydrologic conditions. We evaluated demographic and genetic consequences of upstream and downstream passage using different model assumptions about trashrack spacing and density-dependent effects on the spawning interval. Our genetic results predict that, although reconnection would introduce new alleles to the upstream subpopulation, it would also preserve alleles from the down- stream subpopulation by propagating them in the larger subpopulation above the dam. Our demographic results predict that halving the space between trashracks would have large and unequivocal benefits, whereas the predicted effects of reconnection were smaller and more sensitive to model assumptions. Simulated upstream passage tended to benefit both subpopulations only in the absence of density-dependent limitation. In the presence of density dependence, the combination of halved trashrack spacing and upstream and downstream passage produced the best results. Narrower trashracks kept spawning adults in the upstream segment with spawning habitat, while allowing their progeny to migrate downstream. Screening appears to be the best option for such a species in this configuration of a long river segment acting as a demographic source above a short one acting as a demographic sink.


In the paper, a new spatio-temporal segmentation algorithm is proposed to extract moving objects from video sequences, the sequences were taken by stationary cameras. First, the motion detection is used to achieve the mask representing moving regions with a estimation noise parameter. Which can effectively improve noise immunity. Due to the shortage of the moving video object textures, the eight-neighbor motion detection is present, which is used to smooth the mask boundary and fill the interior holes. Then a morphological filter is applied to refine the moving mask. Second, spatial segmentation is detected by the Canny operator. Then utilize the gradient histogram to select the high threshold to increase the adaptivity of Canny algorithm. Finally, merge the temporal and spatial mask by neighborhood matching algorithm to ensure further reliability and efficiency of our algorithm. Experiments on typical sequences have successfully demonstrated the validity of the proposed algorithm.


This paper employs a standard Tobin-Markowitz framework to analyse the determinants of capital flows into the CIS countries. Using data from 1996-2006, we find that the Russian financial crisis of 1998 has had a profound impact on capital flows into the CIS (both directly and indirectly). Firstly, it introduced a structural shift in the investors' behaviour by shifting the focus from the external factors to the internal ones, e.g. domestic interest and GDP growth rates. Secondly, it also drastically changed the impact of a number of explanatory variables on capital flows into the CIS. Political risk was found to be the second most important determinant of capital flows into the CIS. Additionally, we report some strong evidence of co-movement between portfolio flows into the CIS and CEEC, coupled with strong complementarity between global stock market activity and portfolio inflows into the CIS. Interestingly, external factors tend to be of a higher significance than internal factors for the largest members (Russia, Ukraine and Kazakhstan) of the CIS; whereas domestic variables tend to have a greater impact on the capital flows into the smaller CIS countries.


The United States Supreme Court confronted the issue of a classroom display of the Ten Commandments almost 25 years ago in the case of Stone v. Graham. In that case, the Court struck down a Kentucky statute that required the posting of the Ten Commandments in all public school classrooms. In a per curiam opinion, the Court summarily reversed a decision of the Supreme Court of Kentucky and concluded that the statute violated the First Amendment's Establishment Clause because it had no secular purpose. The outcomes of recent judicial decisions considering the constitutionality of the display of the Ten Commandments have not been uniform. While the courts have all applied similar legal standards, considering both whether the government had a secular purpose for its display and whether the display gave the appearance of government endorsement of religion, their analysis has been far from uniform. Courts have disagreed over a number of critical issues including how to assess government expressions of a secular purpose, how to evaluate the place of the Ten Commandments in the history of American law, how to characterize the historical context of the challenged display, and whether displaying the Ten Commandments along with other documents of secular significance legitimizes a secular purpose for the display and eliminates any risk of government endorsement of religion.


This paper discusses the reasons behind the Lehman Brother's failure. It analyses whether it could be prevented and what measures were necessary. We open the discussion with the factors that led to this event followed by company history. Some of the leading causes were the bazaar for Credit Default Swaps, falsification of financial statement, and unethical behavior of top executives. In the falsification of financial statements, Repo 105 procedure played a major role in creating healthier financial statements for Lehman. Several recommended that the falsification by the top managers dishonored the Sarbanes-Oxley Act. The paper concludes with the supreme size and universal scale of the crisis, and the incomparable reaction of the government, to stabilize the system, calls for a cautious assessment of the financial system.


According to "The Strategy of the Development of the Country to 2020. Active Society. Competitive Economy. Efficient State", the factors of growing importance for the modern and complex development of the nation and the state are the values and standards of behaviour accepted by the society allowing communication and cooperation. They predominantly determine the readiness to take a risk, as well as creative and innovative activities. Moreover, they exert a significant impact on the ability to cooperate and create social capital. They are also gaining greater importance as a development factor.1 This is essential in the contemporary world, in which political, social, economic or cultural transformations generate serious modifications in various


Abstract Objective To investigate the relationship between poor Fe status and overweight or obesity in elderly respondents in South Africa. Design Cross-sectional, observational baseline survey. Setting Sharpeville, South Africa. Subjects A sample size calculation determined a representative sample of 104 randomly selected elderly (≥60 years) respondents. Measurements included weight, height, biochemical and haematological parameters. Measured BMI was used to categorise the respondents into normal weight, overweight and obese groups. Results The majority of the women were overweight (28·4 %) or obese (54·6 %); 58 % of the respondents had normal Fe status, 15 % were classified as Fe depleted, 9 % as Fe deficient and 13 % as Fe-deficient anaemic. Ten per cent of the respondents had low Hb levels with no other low Fe status parameters, and were thus anaemic due to other causes. A significant correlation (r = 0·318, P < 0·001) existed between BMI and high-sensitivity C-reactive protein (hs-CRP). hs-CRP was negatively correlated to serum Fe levels (r = −0·319, P < 0·001). No significant relationships existed between BMI and Fe status parameters. Conclusions A coexistence of obesity and poor Fe status were observed in these elderly respondents. The positive relationship between hs-CRP and BMI indicated chronic inflammation in the higher BMI groups. The negative relationship between hs-CRP and serum Fe indicated that lower serum Fe levels were related to the inflammation linked with higher BMI. A relationship between obesity-related chronic, low-grade inflammation and poor Fe status has been found in adults, but the significance of the current study is that this relationship was also confirmed for elderly persons.


Leitmotifs are recurring themes and can occur in all kinds of creative work, including music, theatre, film, literature and poetry. A leitmotif can serve to aid memory or to bind a work together.It can be used as a device to add coherence to a whole, or to narrate a story without the use of words, adding an extra semiotic level to the narrative. So what to do when a recurrent theme has to be audio described in a film? It may be an image, a sound or a tune, which is associated with an emotion or with a key element in the development of the film narrative. Should it be explicitly highlighted by the description?The article begins with a brief presentation of leitmotif in films, providing various examples. It then focuses on one experiment, using eye-tracking and comprehension questions to test the reception and impact of information delivered by audio description on the user, and measuring how exogenous attention through audio description may impact on and interact with the audience. It is hoped that this article will pave the way toa different approach towards drafting audio description where explicitation is not seen as patronising and subjective, but as an audio narratological featurepeculiarto audio description.


The MPC Omega and Theta models for creep deformation and life prediction have become popular in recent years. Both models offer better prediction than classical constitutive models such as Norton Power law, Bailey-Norton law, and Norton-Soderberg law to name a few. The Omega model uses a strain hardening approach and requires two material constants for creep deformation and life prediction. An analytical solution to the constants are available and it is easy to manipulate and implement numerically. However, the analytical damage of the Omega model predicts an unrealistic linear damage evolution. The Theta model uses a time-hardening approach, and requires four constant that are a function of stress and temperature. For materials under isothermal conditions, with tertiary creep dominant deformation, the Theta model constants can be determined using only two constants. Life prediction using the Theta and Omega models depends on the final creep strain. The final creep strain observed in an experiment is stochastic; dependent on the material, testing conditions, and operator. The statistics of final creep strain must be investigated before the Theta or Omega models can be applied. In literature, some authors add a nonlinear damage variable to the Theta model; however, critical damage at rupture is not unity violating the assumptions of continuum damage mechanics. There is a superior Sin-hyperbolic continuum damage model available in the literature that can be used to overcome these problems. It is hypothesized that a functional relationships exist between the three models and these relationships can be exploited to achieve more accurate and easy to implement creep deformation and life predictions. In this study, the relationships between the constants of MPC Omega, Theta, and a Sin-hyperbolic CDM models are determined analytically. The sin-hyperbolic model incorporates a continuum damage variable in the creep strain rate equation. The damage function exhibits a more realistic elliptical path and is constructed such that damage is always unity at rupture. This function facilitates conversion of one models' constants to the constants of the other two. The relationships between the constants are identified, while maintaining dimensional homogeneity. Using the derived relationships, the three models can be easily compared and the disadvantages of each respective model can be avoided. Experimental data at four different configurations of stress (6.3 to 36.5 ksi) and temperature (1200 to 1800°F) (sixteen data sets) for Hastelloy X is used to compare the models. Creep rupture data at seven temperature levels (600 to 1000°C) and a wide stress range (5 to 500 MPa) is used to analyze life prediction. The constants for each model are determined. Using one models' constants and the derived relationships; the predictions of the other two models are generated. It is observed that the relationship generated curves agree with experimental data.Finally, it is demonstrated that using the derived relationships, the most useful aspects of each model can combined. An elliptical damage evolution curve is obtained for the Omega model. The final creep strain rate dependency problem of the Theta model can be avoided. It is observed that the Sinh model becomes more flexible and easy to implement.Copyright © 2016 by ASME


We need conceptual modelling languages to gain domain knowledge in the requirements engineering and analysis phases of an IS development project. These languages should serve an IS expert as means of communication between him or her and the domain expert. Many different modelling languages have been used for conceptual modelling. Consequently, questions relating to the quality of these languages have arisen. Wand, Weber and others have evaluated these languages using an ontology. Each of the languages was found to contain certain deficits. Because our aim is to construct a language without such deficits, we propose the opposite technique. We develop an ontologically clear modelling language for process modelling with the help of the BWW representational model. In addition to this modelling language, we introduce a process model which guides model creation. Both components form a conceptual modelling method.


Maximizing water returns to river basins by managing interbasin transfers is one of several major objectives guiding the ongoing development of Georgia's first Comprehensive State-wide Water Management Plan. Interbasin water transfers currently play a significant role in meeting water supply needs throughout the metropolitan Atlanta area. Continuing population growth across northern Georgia has heightened concern over the continuing use of interbasin transfers as a primary water management tool because of potentially negative environmental and economic impacts to the river basin of origin. This paper investigates the availability and quality of relevant environmental information for assessing the potential adverse environmental effects of interbasin transfers to river basins of origin in Georgia. Existing information describing environmental attributes of 14 sub-basins in seven river basins is compiled using GIS, and subbasins are ranked and analyzed with respect to natural resource values, common trends, data gaps, and its ability to support water planning efforts and decisions regarding interbasin transfers.


Colloidal nanoparticles exhibit unusual individual and collective behaviour, often associated with interesting electrical, optical or electromagnetic properties. Thiol-passivated colloidal gold nanoparticles possess in addition a self-organising property, which, when the particles are deposited on a substrate, yields a plethora of fascinating patterns. The conditions of formation of these patterns are investigated, in order to understand the principles of - and gain control over - non-equilibrium self-organisation following drop evaporation.

The work presented in this thesis relies mostly on experimental observations, although the results are supported by numerical simulations carried out in the group and based on modified versions of the model developed by Rabani et al. in 2003 [1]. A novel deposition method is introduced, which provides controllable conditions for the occurrence of a wide variety of patterns, including close-packed monolayers of nanoparticles. Pattern and surface characterisation is achieved by combined microscopy techniques - atomic force microscopy (AFM) and real-time contrast-enhanced optical microscopy. The influence on pattern formation of the nanoparticle-solvent-substrate interactions is studied by altering the physical properties of all three components (substrate, solvent and nanoparticles).

The experimental set-up allows a meniscus-driven evaporation of the solvent of the nanoparticle solution and enables monitoring of drying front instabilities during the dewetting process. The effects of these instabilities on pattern formation are investigated and highlight a strong contribution of free excess ligands.

We have focused on two specific types of patterns which emerge in these experiments : fingering structures and nanoparticle rings. The former are reminiscent of patterns that form in a number of other systems, a process usually called "viscous fingering". A thorough investigation reveals that the mechanism of formation of such patterns involves the combination of specific experimental conditions and at least two different dewetting processes, with different time and length scales. A "pseudo-3D" Monte Carlo model recreates such conditions and yields simulated results which are in good qualitative and quantitative agreement with experimental results. On the other hand, nanoparticle rings, although they are a recurrent type of pattern observed in nanoparticle assemblies [2, 3], form according to a mechanism which is not yet fully understood. We show however that wetting properties play a central role in ring formation and growth. As in the case of fingering structures, a narrow range of parameters has been determined, via an exhaustive experimental investigation, which favours the occurrence of nanoparticle rings.

For all the nanoparticle assemblies studied in this thesis (close-packed monolayers, fingering structures and nanoparticle rings), the deduction of pattern formation mechanisms from experimental observation (and simulations) relies on the very high degree of reproducibility that it is possible to attain using the combination of a meniscus-driven evaporation, a very fine tuning of experimental conditions and nanoparticle-solvent-substrate interactions, and a systematic cross-characterisation by complementary imaging techniques.


In the era of big data, it is often the rare categories that are of great interest in many high-impact applications, ranging from financial fraud detection in online transaction networks to emerging trend detection in social networks, from network intrusion detection in computer networks to fault detection in manufacturing. As a result, rare category characterization becomes a fundamental learning task, which aims to accurately characterize the rare categories given limited label information. The unique challenge of rare category characterization, i.e., the non-separability nature of the rare categories from the majority classes, together with the availability of the multi-modal representation of the examples, poses a new research question: how can we learn a salient rare category oriented embedding representation such that the rare examples are well separated from the majority class examples in the embedding space, which facilitates the follow-up rare category characterization? To address this question, inspired by the family of curriculum learning that simulates the cognitive mechanism of human beings, we propose a self-paced framework named SPARC that gradually learns the rare category oriented network representation and the characterization model in a mutually beneficial way by shifting from the 'easy' concept to the target 'difficult' one, in order to facilitate more reliable label propagation to the large number of unlabeled examples. The experimental results on various real data demonstrate that our proposed SPARC algorithm: (1) shows a significant improvement over state-of-the-art graph embedding methods on representing the rare categories that are non-separable from the majority classes; (2) outperforms the existing methods on rare category characterization tasks.


Scanning through laser field strength and ellipticity, we show that the ellipticity anomaly in harmonic generation in C60 results from uneven saturations at different laser ellipticities. The smaller the laser ellipticity is, the faster the harmonic generation yield saturates with the laser strength. Harmonic generations at nonzero ellipticities take advantage of the earlier saturation at zero ellipticity, continue to grow with the laser field strength and eventually surpass the zero-ellipticity harmonic generation, which leads to the anomalous dependence. The theory predicts that the ellipticity dependence in C60 is much richer than those found in atoms: With an increase in laser field strength, a single maximum can be split into multiple maxima, and the global maximum comes back to zero ellipticity and reclaims its dominance over all other peaks.


The hypothesis that a localized lordosis, or tethering of the posterior elements of the spine, is the primary cause of the vertebral rotation in idiopathic scoliosis was investigated in anatomic specimens of human and calf spinal columns. The specimens were axially loaded with and without a posterior tether created using Zielke instrumentation. Lateral deflection and axial rotation were monitored roentgenographically. The vertebrae of tethered spines showed increased rotation in the direction associated with idiopathic scoliosis. The spinous processes moved toward the concavity at the apex of the induced lateral curve. Conversely, untethered spines either exhibited little rotation or rotated in the opposite direction; the spinous processes moved toward the convexity of the curve. Rotations toward the convexity occur in rotational kyphosis. Thus the hypothesis that idiopathic scoliosis is a rotational lordosis is substantiated; the characteristic rotation can be explained with the aid of a geometric model.


Abstract Geothermal fluids form by the infiltration, heating and circulation of meteoric waters in the Earth's crust. Rock-water reactions, boiling and condensation processes influence the chemistry of the fluids. The composition of geothermal fluids ranges from that of gold-depositing, dilute waters to saline, oil-field brines; as such they form a link between these two aqueous systems. Techniques developed to examine the processes active in geothermal systems may find valuable application in gold exploration and hydrocarbon reservoir modelling. The concept of hydrological regime is introduced and applied to recognising deposits of geothermal activity, the level of preservation and permeable, potentially gold-bearing zones in ancient epithermal systems. Mixing models, such as Cl-enthalpy plots, and geothermometry can aid identification of breakthrough of edge waters and casing damage. Differences in the equilibration time of geothermometers may enable the thermal profile or history of the reservoir to be developed. Statistical models enable major controls or sources of the solutes to be isolated, and aid in the correlation of formation waters between wells.


Szolnok lies in the heart of the Great Hungarian Plain known as the capital city of the River Tisza, a Pan-European rive


Dysfunction of the corneal endothelium due to cell loss caused by aging, disease or trauma can lead to severe visual impairment and blindness. Traditionally, dysfunctional endothelia are managed surgically, by removing the entire central cornea and transplanting either donor corneal tissue (penetrating keratoplasty), or just endothelia isolated from donor corneas. As in many cases it is only the corneal endothelium requiring replacement, many attempts were made over the last decades to develop an endothelial substitute, thereby precluding the need for the use of full donor corneas. This article reviews these attempts, which include artificial membranes, cell-coated corneal transplants, and cell-coated membranes. The presumption of an artificial corneal endothelium capable of duplicating the transendothelial ion-and-fluid transport function is examined in light of the latest hypotheses regarding the mechanism of this function.


ABSTRACT Personal hygiene accounts for 30–45% of water use in households in Organisation for Economic Co-operation and Development (OECD) countries, and of this water, the greatest proportion is used for showering. More efficient showers can be achieved by using efficient technologies – mainly efficient showerheads – as well as through the adoption of sustainable habits, such as reducing shower frequency and duration. A review of the websites of water utilities in cities of OECD countries shows little effort to promote water-saving shower habits. Addressing this shortcoming would improve the sustainability of water use, compared with the current focus on efficient technologies.


Following allegations of environmental contamination, a scheme for the surveillance of animal health on dairy farms in the vicinity of a large complex of chemical industries in the region of Cork harbour was initiated in 1991. Multidisciplinary investigations were undertaken as a result of unusual incidents of animal ill-health or decreased productivity, and an explosion and fire at one of the industrial plants. There was no evidence that exposure to environmental pollutants caused variations in either productivity or the incidence of disease. Many incidents which might have been linked with environmental pollution were found to have other causes. A broad database of animal disease incidence, productivity and blood composition has been established, and a bank of tissues taken from animals submitted for routine slaughter has been frozen, so that they may be analysed for toxins if required. The main difficulty encountered during the study was inadequate disclosure of information by some herd owners.


SIR,-Professor W E Waters and others (12 November, p 1442) report an unexpected higher mortality in women aged 45 to 64 years who did not have headaches or migraine compared with those who suffered from these ailments. I wonder if this finding is related to the fact that women who are susceptible to migraine are less likely to have ever smoked. In a survey of 336 patients attending the Charing Cross Hospital migraine clinic there were significant differences between smokers and non-smokers.1 2 Smokers had more frequent and severe attacks, they were more likely to attend the hospital for acute treatment, and there was a 10-fold drop in the number of attacks when they stopped smoking. 74%° of the patients were women, and eight times more women than men aged over 40 had never smoked, suggesting an early intolerance to smoking. Migraine sufferers may be protected from other diseases as they are more likely to avoid alcohol and foods with a high amine content, such as cheese and chocolate, which they have discovered will precipitate their attacks.3


The ubiquitin-proteasome proteolytic pathway is pivotal in most biological processes. Despite a great level of information available for the eukaryotic 26S proteasome—the protease responsible for the degradation of ubiquitylated proteins— several structural and functional questions remain unanswered. To gain more insight into the assembly and function of the metazoan 26S proteasome, a two-hybrid-based protein interaction map was generated using 30 Caenorhabditis elegans proteasome subunits. The results recapitulate interactions reported for other organisms and reveal new potential interactions both within the 19S regulatory complex and between the 19S and 20S subcomplexes. Moreover, novel potential proteasome interactors were identified, including an E3 ubiquitin ligase, transcription factors, chaperone proteins and other proteins not yet functionally annotated. By providing a wealth of novel biological hypotheses, this interaction map constitutes a framework for further analysis of the ubiquitin-proteasome pathway in a multicellular organism amenable to both classical genetics and functional genomics.


This article examines journalists' narratives of the constellations of factors that shaped the coverage of the 2011–2012 social protest in Israel, and how journalists used the protest to negotiate their roles, practices, and values against the backdrop of their own professional and economic struggles. Based on in-depth interviews with reporters and editors who were involved in the coverage of the protest movement, this article analyzes journalists' interpretations and negotiations of the various influences on their work during the two major waves of the protest. An analysis of patterns of collision and concurrence between individual, organizational, and professional domains of influence in journalists' narratives shows that while the norm of objectivity remains a key site of tension in relation to other factors, considerations of newsworthiness are constructed as complementing and justifying all other types of influence. An examination of diachronic patterns suggests that journalists' individual conditions and positions play a greater role in journalists' narratives in the first stage of the protest, giving way to professional values and organizational economic considerations in later stages. Although these findings further complicate the protest paradigm, they also show a dominant pattern of "paradigm repair" at the level of both journalists' professional ideology and protest coverage.


Background To date, insertion torque value (ITV) and implant stability quotient (ISQ) obtained by the Osstell instrument are common clinical methods to assess the initial stability of an implant for a predictable loading procedure. The aim of this current study is to evaluate the ITV and ISQ as stability parameters as part of the decision-making protocol in the adoption of immediate loading in fresh extraction sockets. Materials and Methods A total of 41 tapered implants were allocated into two groups: the test group (n = 11; 3 males and 8 females; mean age: 62.8 ± 10.7) which received 18 implants as type 1 fresh extraction sockets after teeth removal and the control group (n = 7; 4 males and 3 females; mean age: 65.4 ± 9.7) which received 23 implants placed in healed sockets for a period of at least 3 months. Both the ITV and ISQ data were recorded at the time of insertion (t0). Since ITV (test group) and ITV/ISQ (control group) values were useful for the immediate loading protocol, a screw-retained temporary crown was immediately loaded. ISQ values were recorded after a healing period of 4 months (t1). Results ITV mean values at t0 in test and control groups were, respectively, 48.61 ± 15.39 and 70.47 ± 14.71, whereas ISQ mean values were 57.55 ± 1.93 and 72.86 ± 5.25, respectively, showing a statistically significant difference (p value < 0.001). ISQ mean values at t1 in either the test or the control group were 68.68 ± 4.20 and 74.54 ± 4.17, not showing a statistical difference. The implant survival rate was 100% in both groups, and no surgical and prosthetic complications were reported during the study. Conclusion In conclusion, this study remarked the presence of a residual gap that influenced the ISQ during implant insertion in fresh extraction sockets making this parameter not sufficient for a conclusive decision in the immediate loading, whereas the ITV alone showed to be the best parameter for a final substantial decision.


Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide, representing a group of disorders characterized by loss of cardiac function as a result of irreversible damage to cardiomyocytes which results in scar tissue formation. Stem cell therapy are a viable option to improve cardiac function and to promote the repair and regeneration of the myocardium. Several preclinical and clinical trials have shown that transplantation of functional and healthy SCs can promote myocardial regeneration and repair. Here, we focus on the therapeutic applications of embryonic stem cells and adult stem cells to human CVD.


This paper investigates the impact of inflation accounting on key financal ratios. To this end, the financial statements of 132 companies listed in the Istanbul Stock Exchange (ISE) are studied. An analyis of paired samples t test has been conducted on the financial ratios of the companies. The results show that a significant difference between adjusted cost based financial ratios and historical cost based financial ratios occurs only for current, ratios, equity ratios and noncurrent turnover ratios. The study does not cover companies operating in the financial sector. The companies reporting in accordance with IFRS for the studied periods that spans 2001-2004 are not included in the study either. The study offers valuable information as to analysing companies operating in hiper inflation economies.


This paper shows how the dips and secular dimming in the KIC8462852 light curve can originate in circumstellar material distributed around a single elliptical orbit (e.g. exocomets). The expected thermal emission and wavelength dependent dimming is derived for different orbital parameters and geometries, including dust that is optically thick to stellar radiation, and for a size distribution of dust with realistic optical properties. We first consider dust distributed evenly around the orbit, then show how to derive its uneven distribution from the optical light curve and to predict light curves at different wavelengths. The fractional luminosity of an even distribution is approximately the level of dimming times stellar radius divided by distance from the star at transit. Non-detection of dust thermal emission for KIC8462852 thus provides a lower limit on the transit distance to complement the 0.6 au upper limit imposed by 0.4 d dips. Unless the dust distribution is optically thick, the putative 16 per cent century-long secular dimming must have disappeared before the WISE 12 mum measurement in 2010, and subsequent 4.5 mum observations require transits at >0.05 au. However, self-absorption of thermal emission removes these constraints for opaque dust distributions. The passage of dust clumps through pericentre is predicted to cause infrared brightening lasting tens of days and dimming during transit, such that total flux received decreases at wavelengths <5 mum, but increases to potentially detectable levels at longer wavelengths. We suggest that lower dimming levels than seen for KIC8462852 are more common in the Galactic population and may be detected in future transit surveys.


A total of 14 patients had operations for massive colonic haemorrhage. Of the seven who had a right hemicolectomy, four had the bleeding site localised, and three had only 'equivocal' indications of a right-sided source. One of these rebled 11 months later, but all survived and are well. Of the remaining patients, two had left-sided resection, one requiring an immediate second operation for rebleeding, and five, subtotal colectomy, of whom two died. A literature review confirms the suggestion that if the bleeding site has not been identified but, nevertheless, there are clues suggesting it to be right-sided, the best results will be obtained by right hemicolectomy. Left-sided resection should be used only when there is proof of left-sided bleeding, otherwise there will be an unacceptably high mortality. No clues, 'equivocal' indications of a left-sided source, or the presence of bilateral disease, should lead the operator to perform subtotal colectomy.


Groups, companies, and organizations identify themselves via symbols. Symbols have the potential to create group identity and at the same time create group boundaries, thus allowing for achieving the benefits of cooperation by ingroup members. We use a laboratory experiment to study the role of group identity, created by the use of symbols, in mitigating the holdup problem. As a team symbol we employ color t-shirts. We find that the usage of t-shirts itself does not create a strong enough group identity to mitigate the holdup problem. However, in our previous research, we found that group identity created by t-shirts and a group chat aimed to help team members to solve a task is capable of resolving the holdup problem. These findings are consistent with the everyday practice where organizations often make significant investments in team-building and socialization activities, suggesting that an important objective of such activities might be to strengthen group identity so that it is effective even in highly strategic environments.


Four Middle and Upper(?) Ordovician formations are exposed east of Mazourka Canyon in the Independence Quadrangle. The Chazyan Mazourka formation, approximately 500 feet of limestone and shale, conformably succeeds early Ordovician(?) dolomite and belongs to the Pogonip group. The overlying Barrel Spring formation, approximately 150 feet of Mohawkian sandstone, shale, and limestone, is assigned to the Eureka group. Approximately 200 feet of Mohawkian argillaceous limestone, dolomite, and quartzite make up the unnamed remainder of the Eureka group. Approximately 175 feet of Upper Ordovician(?) dolomite resting on the Eureka group is tentatively assigned to the Ely Springs formation. Silurian rocks disconformably succeed the Ely Springs formation.


Rudimentary supernumerary digits and preauricular skin "tags" are relatively common congenital abnormalities. These abnormalities can present as isolated occurrences or as part of a syndrome. Isolated polydactyly occurs in approximately 0.3 of 1000 live births in white populations and from 3.6 to 10 of 1000 live births in black populations. 1,2 Preauricular tags are also relatively common anomalies. Little attention has been paid to the treatment of these lesions, but pediatricians are commonly taught to ligate the base of these lesions with suture material as a simple, inexpensive form of removal. We recently saw a patient in whom a secondary bacterial infection developed after suture ligation of a supernumerary digit ( Figure ), prompting us to reevaluate this technique and consider the potential problems inherent in this traditional form of treatment. Suture ligation of the base of supernumerary digits and preauricular skin tags is a commonly practiced technique in pediatrics. Although documentation


Today the borderless internet is used by state and non-state actors to manipulate information and societies in ways that were unheard of 50 years ago. Malicious actors can rapidly conduct information maneuvers with little cost at unprecedented scales to achieve far reaching consequences across the internet. They do this byexploiting features of the various social media platforms and the way humans naturally understand what they read and hear. These cyber-mediated threats to open anddemocratic societies have led to an emerging discipline known as social cybersecurity. While various aspects of these campaigns have been explored, little research hasfocused on the campaign level of engagement. Our research seeks to answer the question: How can information warfare campaigns be identified and characterizedquickly? Our goal is to 1) Improve understanding of information operations, and 2) Develop techniques to rapidly identify key factors such as bots and memes.To accomplish this, I present the strategic context of the information warfare that we see today, and identify and define information warfare forms of maneuver. I developvarious supervised and unsupervised methods to identify bots at four different data granularities. I present a deep learning model to classify memes as well as studythe evolution of memes within a conversation. I present a template for understanding the major components of an information campaign and develop automatic waysto populate this template for a specific event. Finally, we present a Bot, Cyborg, and Troll Field Guide to help analysts and the general population understand these entities.


Carbonaceous materials (CM), such as activated carbons or biochars, have been shown to significantly reduce porewater concentrations and risks by binding hydrophobic organic compounds (HOCs) present in aquatic sediments. In the present study, the authors review the current state‐of‐the‐art use of CM as an extensive method for sediment remediation, covering both technical and ecological angles. The review addresses how factors such as CM type, particle size and dosage, sediment characteristics, and properties of contaminants affect the effectiveness of CM amendment to immobilize HOCs in aquatic sediments. The authors also review the extent to which CM may reduce bioaccumulation and toxicity of HOCs and whether CM itself has negative effects on benthic species and communities. The review is based on literature and datasets from laboratory as well as field trials with CM amendments. The presence of phases such as natural black carbon, oil, or organic matter in the sediment reduces the effectiveness of CM amendments. Carbonaceous material additions appear to improve the habitat quality for benthic organisms by reducing bioavailable HOC concentrations and toxicity in sediment. The negative effects of CM itself on benthic species, if any, have been shown to be mild. The beneficial effects of reducing toxicity at low CM concentrations most probably outweigh the mild negative effects observed at higher CM concentrations. Environ. Toxicol. Chem. 2012;31:693–704. © 2012 SETAC


Interactive training approaches are used in industry and business for on-demand and compulsory training. However, use by counselor educators has been slow in developing this potential area of growth. Given current technologies, uses for interactive, easily created materials can become an important addition to the training of professional counselors in classrooms, by distance learning, in web-based training and, importantly, as a stand-alone product for increasing skill. Recently a selfdirected interactive CD-ROM training program, "Clinical Supervisor Training: An Interactive Training Program for the Helping Professions," was developed by the authors. The training package presents a format for the use of current technologies for enhancing training and teaching efforts of educators, particularly counselor educators. The focus of the program is clinical supervision. While this discipline lends itself to the use of computer-based interactivity, it is the premise of this document that many other areas of teaching and learning also can be enhanced by these methods. In fact, while this document covers details of the creation and development of the CD-ROM and training manual that accompanies the program, similar processes can be adapted for almost all areas within counselor education. (Author) Reproductions supplied by EDRS are the best that can be made from the on ma! document. On-Demand Interactive Clinical Supervision Training: Using Multimedia for Building Basic Skills in Supervision


The most important thing to remember about the drowning of New Orleans is that it wasn't a natural disaster. It was a man-made disaster, created by lousy engineering, misplaced priorities and pork-barrel politics. Katrina was not the Category 5 killer the Big Easy had always feared; it was a Category 3 storm that missed New Orleans, where it was at worst a weak 2. The city's defenses should have withstood its surges, and if they had we never would have seen the squalor in the Superdome, the desperation on the rooftops, the shocking tableau of the Mardi Gras city underwater for weeks. We never would have heard the comment "Heckuva job, Brownie." The Federal Emergency Management Agency (fema) was the scapegoat, but the real culprit was the U.S. Army Corps of Engineers, which bungled the levees that formed the city's man-made defenses and ravaged the wetlands that once formed its natural defenses. Americans were outraged by the government's response, but they still haven't come to grips with the government's responsibility for the catastrophe. They should. Two years after Katrina, the effort to protect coastal Louisiana from storms and restore its vanishing wetlands has become one of the biggest government extravaganzas since the moon mission—and the Army Corps is running the show, with more money and power than ever. Many of the same coastal scientists and engineers who sounded alarms about the vulnerability of New Orleans long before Katrina are warning that the Army Corps is poised to repeat its mistakes—and extend them along the entire Louisiana coast. If you liked Katrina, they say, you'll love what's coming next.


This paper examines the convergence process in Brazil over the period of 1985-2004, giving a special attention to the role of human capital as a conditioning factor to convergence. It examines how different levels of human capital influence growth in different regions of Brazil. Different measures of human capital are used in the growth regressions and the results show that they play a significant role in explaining the growth process. The evidence indicates that different levels of human capital have different impacts on the per capita income growth, depending on the level of development of the states. Lower levels of human capital explain better the convergence among the less developed states and higher levels of human capital are more adequate among the more developed states. The impact of the relative intermediate levels of human capital on growth is stronger in all samples, suggesting the existence of threshold effect in education. JEL classification: O, O1, O15


ABSTRACT This paper considers the situation of students with a disability studying in institutions of higher education, and how they can be helped to achieve their academic aims with the minimum of personal discomfort. Three main groups of students are identified—ambulant disabled and wheelchair bound students, students with partial or complete loss of sight, and students with hearing impairments—and their particular problems and needs are discussed. Strategies for helping them achieve their academic aims are offered, including the suggestion that each institution should formulate a statement of policy in relation to admitting such students so as to ensure their welfare while they are studying.


The purpose of this study was to examine the efficiency of Texas public school districts through Data Envelopment Analysis. The Data Envelopment Analysis estimation method calculated and assigned efficiency scores to each of the 931 school districts considered in the study. The efficiency scores were utilized in two phases. First, the school district efficiency scores were combined with school district student achievement to evaluate effectiveness with efficiency. A framework was constructed to graph the scores on an x-axis of student achievement scores and a y-axis of efficiency scores to further illustrate the data. The framework was evaluated with the full statewide sample and with school districts categorized into similar peer groups. Then, using variables selected from related scholarly literature, a regression analysis identified which factors impacted school district efficiency statewide. The non-discretionary variables included in the study were total student enrollment, the percentage of non-white students and the percentage of economically disadvantaged students. The discretionary variables selected included the teacher-to-student ratio, teachers' average years of experience, the percentage of teachers with master's degrees and the average teacher base salary. Amongst the seven factors selected for regression analysis, five statistically significant variables were identified as impacting statewide school district efficiency. All three non-discretionary variables were identified as statistically significant on efficiency and included total student enrollment, the percentage of non-white students and the percentage of economically disadvantaged students. Two discretionary factors showed statistically significant effects on efficiency which included teachers' average years of experience and the percentage of teachers with master's degrees. The teacher-to-student ratio and the average teacher base salary were ineffective in predicting efficiency. This study contributed to the understanding on educational efficiency. Data Envelopment Analysis has been employed mainly in the private sector to analyze efficiency in economics and business organizations. This study added to the educational research on selecting Data Envelopment Analysis as a primary estimation method for analyzing the efficiency of school systems.


The electrical properties of organic field‐effect transistors (OFETs) are usually characterized by applying models initially developed for inorganic‐based devices, which often implies the use of approximations that might be inappropriate for organic semiconductors. These approximations have brought limitations to the understanding of the device physics associated with organic materials. A strategy to overcome this issue is to establish straightforward connections between the macroscopic current characteristics and microscopic charge transport in OFETs. Here, a 3D kinetic Monte Carlo model is developed that goes beyond both the conventional assumption of zero channel thickness and the gradual channel approximation to simulate carrier transport and current. Using parallel computing and a new algorithm that significantly improves the evaluation of electric potential within the device, this methodology allows the simulation of micrometer‐sized OFETs. The current characteristics of representative OFET devices are well reproduced, which provides insight into the validity of the gradual channel approximation in the case of OFETs, the impact of the channel thickness, and the nature of microscopic charge transport.


This paper pursues the question 'who needs the nation?' which was first posed by Kobena Mercer, the Black British cultural critic, in Welcome to the Jungle (1994). It interrogates not just the proposition of who needs the nation as a fixed referent, but who can afford to be content to be contained by its disciplinary boundaries. These are questions of interest to practitioners committed to understanding what the ramifications are for national histories in the wake of postcolonial studies and work around diasporic communities and subjects. Who writes—who even sees—the histories of subjects exiled from the 'national body', those refugees (deliberate or otherwise) from national history and its disciplinary regimes—before the 20th century, in the European context? Who questions the apparent naturalness of the nation as an analytical framework in western histories? And, finally, what does this question mean for the sovereignty of Greater Britain, whose historiography has traditionally been one of the technologies of the national state and which is in the process of being challenged and refigured through the analytics of culture, postcolonialism and feminism?


Introduction and purpose: Physical activity is an important component of health at old age and energy expenditure vary according to level of physical activity. The current study aimed to assess physical activity-related energy expenditure and metabolic equivalent of elderly in Kashan, Iran. Materials & Methods: This descriptive cross-sectional study was conducted among 400 elderly (aged more than 60 years old) attending to health care centers of Kashan. The sampling method in this study was multiple-stage cluster sampling. International Physical Activity Questionnaire was used to calculate physical activity and the metabolic equivalent. Data analyzed using SPSS version 16 by employing variety of tests including descriptive statistics, Kolmogorov-Smirnov test, Kruskal-Wallis test and regression. The significance level for all the tests were considered p0.05. Findings: The results of this study indicated that average metabolic expenditure of elderly was 364.84 ±326.21 (IQR=222). Majority of elderly (%79.2) placed in low energy expenditure category and mainly (%87.2) had low levels of physical activity. Our findings showed a significant relationship between the average energy expenditure with physical activity level (p=0.001). According to the results of regression analysis, walking (p=0.001), personal affairs (p=0.001), housekeeping Affairs (p=0.001), activities related to leisure time (p=0.001) and sedentary activities (p=0.001) were significant predictors of energy expenditure among elderly. Conclusion: The results of current study showed that elderly had low level of energy expenditure and physical activity. Thereby, it is recommended to provide opportunities for physical activity at health-care centers and educate staffs for motivating elderly to have an active life.


Adhesion properties of diamond thin films are essential to their performance in technical applications. To obtain the adhesive strength precisely and quantitatively has been the frontier issue to the related scientists and engineers. In this paper, a new experimental equipment for blister tests was designed purposely and fabricated considering related influencing facts. A free-standing window of diamond thin film with the support of silicon wafer was obtained by the aid of photolithography and anisotropic wet etching technology so as to improve the precision of quantitative adhesion measures of diamond films. The mechanics for calculating the quantitative driving force of blister-induced delamination of diamond thin film is presented, which is on base of intensive modeling and simulation. The laser interferometer measurement with fine solution was used to pick up dynamic signals of diamond thin film bulge deformation in micrometer scale and the relationship demonstration of stress to strain of the diamond thin film was available, as a consequence, the adhesive strength could be obtained precisely and quantitatively by the valid model. The paper confirms the accessibility to precise quantitative adhesion measures of diamond films and the results will be beneficial to wide application of diamond thin films in the related fields.


Initial-pressed juice is an important intermediate product in cane sugar industry, and sugar brix is a key indicator for evaluating sugar quality. Real-time evaluation of sugar quality requires determining the content of sugar brix in all steps of the cane sugar process. Near-infrared (NIR) spectroscopy is simple, rapid and non-destructive technologies on the analysis of material contents. In this study, the chemometric algorithm of parameter- combined tuning of Savitzky-Golay (SG) smoother and Partial Least Squares (PLS) regression was utilized for NIR analysis of sugar brix contents in sugarcane initial-pressure juice. The algorithms of combined optimization of SG smoother and PLS regression was achieved and the calibration models were optimally established by screening the expanded 540 SG smoothing modes and the 1-30 latent valuables (LV). The optimized models have high predictive accuracy. These results confirm that the combined optimization of SG smoothing modes and PLS LVs is effective in the quantitative determination of sugar brix contents in sugarcane initial-pressure juice, and that


This article describes the approach taken by First Interstate Services Company to reduce data processing costs by centralizing the procurement of hardware, software, and services. Because this functional centralization was counter to First Interstate's decentralized culture, its formation and development required careful planning and implementation to gain acceptance. Over time, beneficial innovations and significant, well-documented cost reductions generated acceptance and support for this centralized function. This article identifies key factors for successful centralization of data processing procurement in organization and describes future challenges facing the function.


This research aims to apply confirmatory factor analysis to identify the digital transformation components for higher education institutions. The research sample consisted of 300 personnel from agencies within higher education institutions, which are higher education institutions under the Ministry of Higher Education, Science, Research and Innovation, Thailand that use the database system on educational quality assurance called Commission on Higher Education Quality Assessment online system (CHE QA Online). The selection was the result of multi-stage random sampling from 100 higher education instructions. The research tool was an online questionnaire form on factors influencing the success of information systems in the digital transformation for higher education institutions by 5-level rating scale based on the Likert's scale. The result revealed that digital transformation factor consistent with empirical data (p-value = 0.860), which consist of 6 components: 1) Strategy 2) Process 3) Product/Service 4) People 5) Data) and 6) Technology. The research findings help higher education institutions prepare for the elements necessary for the institutional transformation to a digital organization.


Pure thin films of Co1.7Fe1.3O4 spinel iron cobaltites were prepared for the first time by radio frequency sputtering. Such films are made of small crystallites of about 20 to 30 nm in diameter. Because Co1.7Fe1.3O4 films have a composition located in the miscibility gap of Fe3O4–Co3O4, they can be submitted to spinodal transformation below about 900 °C. This transformation was also confirmed at 600 °C by X-ray diffraction and transmission electron microscopy studies. It was demonstrated however that this spinodal transformation occurs after only a few hours at low temperature. Indeed, after annealing in air at 300 to 450 °C for a few hours, the spinodal transformation leading to two-phase spinels, one rich in iron and the other rich in cobalt, was clearly revealed by Raman spectroscopy and electrical measurements.


Diagnostic methods, used in the contemporary medical practice, consist of a combination of distressing invasive (bronchial biopsy, bronchoalveolar lavage) and semi-invasive (induced sputum technique) methods. Monitoring of specific molecules produced during pathological processes in biological matrices is a relatively new technique which represents an alternative way of an entirely non-invasive and comfortable method. The principle is based on the quantification of specific substances - "biomarkers", which are considered to be objectively measurable indicators of a physiological/pathological condition of the organism. Unlike non-specific matrices such as blood plasma (reflecting the state of the whole organism), the exhaled breath condensate is a specific matrix. Concentration levels of biomarkers in the latter matrix evidence the pathological process only in the airways and lungs. Typical molecules to be monitored include H2O2, leukotrienes, prostaglandins, lipoxins and prostanoids.


This study examines whether or not having an internal or external strategic focus interacts with prior experience in small business to impact perceived organizational performance. Utilizing a sample of 237 small business owners from the southeast U.S., a factorial ANOVA and Regression Analysis were used to test hypotheses related to these constructs. Results indicated that utilizing an internal focus was associated with higher performance among both experienced and inexperienced small business owners; however, an external focus was only positively related to performance for inexperienced business owners. No overall difference in performance was found for experience itself.


Multiple Input Multiple Output (MIMO) system has several input and output antennas for executing the data transmission. Channel Estimation (CE) is required in MIMO, to achieve the effective signal transmission over the various amount of antennas. By using CE over the MIMO, the noiseless data transmission is performed. Hence in this paper, a Multi-layer Neural Network (MNN) is used for identifying the CE and this system is named as Multi-layer Neural Network-MIMO-Digital Filter (MNN-MIMO-CE) is proposed for blind channel equalization. The MNN-MIMO-CE has Feed forward Artificial Neural Network (FANN) with back propagation in Levenberg-Marquardt (LM) algorithm and it has two processes MNN training and MNN testing. LM algorithm is used to train the MNN. These processes are used to provide the CE for different combination of antennas. The performance of the MNN-MIMO-CE method is evaluated in comparison with the existing method [25] through simulations using BER as the performance measure.


In a mobile ad hoc network (MANET), each node has to rely on others to relay its packets. Since most mobile nodes are typically constrained by power and computing resources, some nodes may choose not to be cooperative by refusing to do so while still using the network to forward their packets. Most previous works focus on data forwarding. However, dropping control packets is a better strategy for the selfish nodes to avoid themselves from being asked to forward data packets and hence could conserve resources for their own use. In this paper, we present a new mechanism to detect those selfish nodes. Each node is expected to contribute to the network on the continual basis within a time frame. Those which fail will undergo a test for their suspicious behaviour. Simulation results shows that our scheme could be used to detect selfish nodes in a network.


Modern societies belief life insurance scheme, which is designed to be backbone of man survival, ensure financial security and offers readymade source of long term capital financing for the infrastructural project is capable of combating the besetting problem of man so that life can be made easy and continuous. The dramatic increase in competition within the insurance sector and the needs of insurance by people has concurrently resulted in more policy options being available in Nigeria market. The different types and attributes of life insurance plans are to provide quality in the products, so as to satisfy human wants. This study is carried out to measure the buyers' trade-offs among multi-attributed products and services (utilities) that are derived from purchasing a particular life insurance plan using descriptive statistical analysis (Mean Score). The result show that the policyholders generally are not satisfied with the Life insurance products based on the attributes attached to each of the product.


Abstract We have carried out TEM observations of agates of geode origin and Beltane opals. Optically observable individual fibres in agates are composed of many fine fibres which consist of quartz crystallites of 8 to 100 nm in length stacked together parallel to <112¯0> or <11¯00> with c-axes perpendicular to the fibre elongation. The optically observable systematic striations in agate are found to consist of cyclic alternation of layers due to variation in grain size and porosity. Large quartz crystals, protruding into the spaces of geodes, represent the last stage of formation of these bands, and are merely a continuation of the banding sequence. Nanometre scale textures of cristobalite fibres were revealed in Beltane opals. The cristobalite crystallites have the size of 3 to 20 nm in length and are also stacked together. Our TEM results suggest that embryonic particles were formed in their corresponding growth environments and agglutinated to form fibres.


Casein kinase II (CKII) is a ubiquitous protein kinase composed of two subunits, alpha and beta, that can use both ATP and GTP as phosphoryl donors. Two genes located on two separate chromosomes were identified for CKIIalpha: one on chromosome 20 band 13 with an approximate size of 20 kb and a second on chromosome 11 band 15.5-p15.4 that is the same size as the cDNA of locus 20 kb (1.2 kb) and does not contain any introns. The two genes differ in four amino acids. Recently, it has been demonstrated that a membrane-associated platelet-derived CKII phosphorylates coagulation factor Va. The mRNA encoding the platelet CKII was isolated from fresh human platelets, and the corresponding cDNAs encoding the alpha and beta subunits of human platelet CKII were produced and sequenced. The cDNA for platelet CKIIalpha was found to be 99.7% homologous to the CKIIalpha intronless gene, having the same characteristic amino acid residues at positions 128, 256, 287, and 351. However, the cDNA of platelet CKIIalpha has a different amino acid at position 236 (Arg --> His), which is not found in the intronless gene. The cDNA of the CKIIbeta subunit was completely identical with the sequence of the CKIIbeta subunit isolated from other tissues. Since platelets arise from megakaryocytes, mRNA was isolated from the megakaryocytic cell line MEG-01 and the cDNA for CKIIalpha was cloned and sequenced. The cDNA was found to be identical to the intronless gene found in platelets. We have also investigated the expression of the intronless gene in several other cell lines. Expression of the intronless gene was only found in cell line MEG-01. Our data demonstrate expression of the CKIIalpha intronless gene in megakaryocytes and platelets.


Campylobacter spp. have been identified as etiologic agents in outbreaks and sporadic cases of gastroenteritis in developed countries. In developing countries, most reported Campylobacter infections are in children. Previously reported prevalences of Campylobacter spp. in children in Southeast Asia range from 2.9% to 15%. The frequency and pattern of occurrence of Campylobacter spp. differ between developed and developing countries, especially in the number of cases reported in adults and the presence of any seasonal patterns in occurrence. Although the severity of Campylobacter infection in adults was different between developed and developing countries, the clinical symptoms of infection in adults resulting from infection in developing countries was similar to those in developed countries. Many different animal species maintain Campylobacter spp. with no clinical signs. There do not appear to be significantly different colonization rates of Campylobacter in food animals between developed and developing countries. The role of C. jejuni as a primary pathogen in farm animals is uncertain. C. jejuni can be found in feces of diarrheic and healthy calves and piglets. Campylobacter with resistance to antimicrobial agents have been reported in both developed and developing countries, and the situation seems to deteriorate more rapidly in developing countries, where there is widespread and uncontrolled use of antibiotics resistance was observed at high levels in food animals in both developed and developing countries. Studies suggested an association between antimicrobial use in food animals and the development of resistance in human isolates in developed countries.


We have demonstrated very good performance, high yield Ka-band multifunctional MMIC results using our recently developed 0.25-/spl mu/m gate length pseudomorphic HEMT (PHEMT) manufacturing technology. Four types of MMIC transceiver components-low noise amplifiers, power amplifiers, mixers, and voltage controlled oscillators-were processed on the same PHEMT wafer, and all were fabricated using a common gate recess process. High performance and high producibility for all four MMIC components was achieved through the optimization of the device epitaxial structure, a process with wide margins for critical process steps and circuit designs that allow for anticipated process variations, resulting in significant performance margins. We obtained excellent results for the Ka-band power amplifier: greater than 26 dBm output power at center frequency with 4.0% standard deviation over the 3-in. wafer, 2-GHz bandwidth, greater than 20 pet-cent power-added efficiency, over 8 dB associated gain, and over 10 dB linear gain. The best performance for the Ka-band LNA was over 17 dB gain and 3.5 dB noise figure at Ka-band. In this paper, we report our device, process, and circuit approach to achieve the state-of-the-art performance and producibility of our MMIC chips. >


We present (sub)millimeter line and continuum observations in a mosaicing mode of the massive star forming region Cepheus A East made with the Submillimeter Array (SMA). Our mosaic covers a total area of about 3$'$ $\times$ 12$'$ centered in the HW 2/3 region. For the first time, this observational study encloses a high angular resolution ($\sim$ 3$''$) together with a large scale mapping of Cepheus A East. We report compact and high velocity $^{12}$CO(2-1) emission associated with the multiple east-west bright H$_2$ condensations present in the region. Blueshifted and redshifted gas emission is found towards the east as well as west of HW 2/3. The observations suggest the presence of multiple large-scale east-west outflows that seems to be powered at smaller scales by radio sources associated with the young stars HW2, HW3c and HW3d. A kinematical study of part of the data suggests that the molecular outflow powered by HW2 is precesing with time as recently reported. Our data reveal five periodic ejections of material separated approximately every 10$^\circ$ as projected in the plane of the sky. The most recent ejections appear to move toward the plane of the sky. An energetic explosive event as the one that occurred in Orion BN/KL or DR21 does not explain the kinematics, and the dynamical times of the multiple ejections found here. The continuum observations only revealed a strong millimeter source associated with the HW 2/3 region. High angular resolution observations allow us to resolve this extended dusty object in only two compact sources (with spatial sizes of approximately 300 AU) associated with HW2 and HW3c. Finally, the bright optical/X-Ray HH 168 -- GDD37 object might be produced by strong shocks related with the outflow from HW3c.


Fractures of the acetabulum, the cavity of the hip that hosts the femoral head, are complex to understand, plan, and surgically reduce. Segmenting bone fragments in CT scans is fundamental for assisting surgeons in their therapeutically process and can benefit from recent learning-based advances. In this paper, we extended a learning-based network for the semantic segmentation of six pelvic bones: left and right hip, left and right femur, sacrum, and lumbar spine. This semantic segmentation is then process by a surgeon to separate fracture fragments, similarly to an existing baseline process. Results on 6 fracture cases show a qualitative improvement of the final fragment segmentation quality. Mostly, the segmentation time is statistically significantly reduced from 94 min to 18 min, in mean, which is a promising step towards using such learning-based method in preoperative clinical routine.


BACKGROUND
Pancreatic resections are associated with high morbidity (30% to 60%) and mortality (5%). Synthetic analogues of somatostatin are advocated by some surgeons to reduce complications following pancreatic surgery, however their use is controversial.

OBJECTIVES
To determine whether prophylactic somatostatin analogues should be used routinely in pancreatic surgery.

SEARCH STRATEGY
We searched the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, issue 4), MEDLINE, EMBASE and Science Citation Index Expanded to November 2009.

SELECTION CRITERIA
We included randomised controlled trials comparing prophylactic somatostatin or one of its analogues versus no drug or placebo during pancreatic surgery (irrespective of language or publication status).

DATA COLLECTION AND ANALYSIS
Two authors independently assessed trials for inclusion and independently extracted data. We analysed data with both the fixed-effect and the random-effects models using Review Manager (RevMan). We calculated the risk ratio (RR), mean difference (MD) or standardised mean difference (SMD) with 95% confidence intervals (CI) based on an intention-to-treat or available case analysis. When it was not possible to perform either of the above, we performed per protocol analysis.

MAIN RESULTS
We identified 17 trials (of high risk of bias) involving 2143 patients. The overall number of patients with postoperative complications was lower in the somatostatin analogue group (RR 0.71; 95% CI 0.62 to 0.82) but there was no difference in the perioperative mortality, re-operation rate or hospital stay between the groups. The incidence of pancreatic fistula was lower in the somatostatin analogue group (RR 0.64; 95% CI 0.53 to 0.78). The proportion of these fistulas that were clinically significant was not mentioned in most trials. On inclusion of trials that clearly distinguished clinically significant fistulas, there was no difference between the two groups (RR 0.69; 95% CI 0.34 to 1.41). Subgroup analysis revealed a shorter hospital stay in the somatostatin analogue group than the controls for patients with malignant aetiology (MD -7.57; 95% CI -11.29 to -3.84).

AUTHORS' CONCLUSIONS
Somatostatin analogues reduce perioperative complications but do not reduce perioperative mortality. In those undergoing pancreatic surgery for malignancy, they shorten hospital stay. Further adequately powered trials with low risk of bias are necessary. Based on the current available evidence, somatostatin and its analogues are recommended for routine use in patients undergoing pancreatic resection for malignancy. There is currently no evidence to support their routine use in pancreatic surgeries performed for other indications.


The purpose of this study was to develop a learning model based Commercial Graphic Design project-based learning approach, was chosen as a strategy in the learning product development research. University students as the target audience of this model are the students of the fifth semester Visual Communications Design Studies Program Faculty of Art and Design University of Trisakti. Dick, Carey, and Carey models of Research and Development (R and D) are applied to develop this model. The model consists of the systematic phase used to develop products Commercial Graphics. Results of learning products reviewed by expert instructional design, instructional material expert, and instructional media specialist. A series of formative evaluation session - a review and revision process - undertaken in developing this learning products. The results showed that the learning model Commercial Graphics implemented a project-based approach has been improving learning outcomes better than the target - the students of the fifth semester Visual Communications Design Studies Program Faculty of Art and Design University of Trisakti. The results of the research and development of this model in the category of Good. Product effectiveness learning materials can be seen from the test results of students before reading the book knowledge and test results after reading the book. The average value of pre-test result is 64,4, while the result of posttest result is 78,80 The result shows improvement of learning result, test value shows bigger than 17,36 means, and it can be concluded that the learning materials product can improve student learning outcomes . The result of observation from class also shows result of achievement of indicator with answer yes is, 100%, for opening activity, 98,33%, for core activity.


The deposition conditions of less explored La0.7Sr0.3MnO3 (LSMO) and Bi2Sr2Ca1Cu2O8 (Bi-2212) heterostructures are investigated in terms of two different deposition orders. One is in the order of Bi-2212/LSMO and the other is LSMO/Bi-2212. The experimental results indicate the metal-insulator transition (TMI) and Curie temperature (TCurie) of LSMO as well as the superconducting critical transition (TC) of the Bi-2212 to be very sensitive to the order of deposition. In Bi-2212/LSMO, due to factors such as strain, roughness, and degree of oxygenation, superconductivity is not stabilized to interact with LSMO. Whereas the LSMO/Bi-2212 order of deposition displays both superconductivity and ferromagnetic behavior for a single post annealing condition. In LSMO/Bi-2212, depositing Bi-2212 as a top layer and post annealing in air is crucial to achieve optimal carrier concentration for exhibiting high TC.


Background and purpose Previous studies have documented disparate access to cerebrovascular neurosurgery for patients of different racial and socioeconomic backgrounds. We further investigated the effect of race and insurance status on access to treatment of unruptured intracranial aneurysms (UIAs) and compared it with data on patients with aneurysmal subarachnoid hemorrhage (aSAH). Methods Through the use of a national database, admissions for clipping or coiling of an UIA and for aSAH were identified. Demographic characteristics of patients were characterized according to age, sex, race/ethnicity, and insurance status, and comparisons between patients admitted for treatment of an UIA versus aSAH were performed. Results There were 10 545 admissions for clipping or coiling of an UIA and 33 166 admissions for aSAH between October 2014 and July 2018. White/non-Hispanic patients made up a greater proportion of patients presenting for treatment of an UIA than those presenting with aSAH (64.3% vs 48.2%; P<0.001), whereas black/Hispanic patients presented more frequently with aSAH than for treatment of an UIA (29.3% vs 26.1%; P=0.006). On multivariate linear regression analysis, the proportion of patients admitted for management of an UIA relative to those admitted for aSAH increased with the proportion of patients who were women (P<0.001) and decreased with the proportion of patients with a black/Hispanic background (P=0.010) and those insured with Medicaid or without insurance (P=0.003). Conclusion For patients with UIAs, racial, ethnic, and socioeconomic backgrounds appear to continue to influence access to treatment.


Maintaining effective analgesia during invasive procedures performed under general anesthesia is important for minimizing postoperative complications and ensuring satisfactory patient wellbeing and recovery. While patients under deep sedation may demonstrate an apparent lack of response to noxious stimulation, areas of the brain related to pain perception may still be activated. Thus, these patients may still experience pain during invasive procedures. The current study used anesthetized or sedated cynomolgus macaques and functional magnetic resonance imaging (fMRI) to assess the activationof the parts of the brain involved in pain perception during the application of peripheral noxious stimuli. Noxious pressure applied to the foot resulted in the bilateral activation of secondary somatosensory cortex (SII) and insular cortex (Ins), which are both involved in pain perception, in macaques under either propofol or pentobarbital sedation. No activation of SII/Ins was observed in macaques treated with either isoflurane or a combination of medetomidine, midazolam, and butorphanol. No movement or other reflexes were observed in response to noxious pressure during stimulation under anesthesia or sedation. The current findings show that despite the lack of visible behavioral symptoms of pain during anesthesia or sedation, brain activation suggests the presence of pain depending on the anesthetic agent used. These data suggest that fMRI could be used to noninvasively assess pain and to confirm the analgesic efficacy of currently used anesthetics. By assessing analgesic efficacy, researchers may refine their experiments, and design protocols that improve analgesia under anesthesia.


This paper develops a taxonomy of political regimes that distinguishes between three sets of rights—property rights, political rights and civil rights. The truly distinctive nature of liberal democracy is the protection of civil rights (equal treatment by the state for all groups) in addition to the other two. The paper shows how democratic transitions that are the product of a settlement between the elite (who care mostly about property rights) and the majority (who care about political rights), generically fail to produce liberal democracy. Instead, the emergence of liberal democracy requires low levels of inequality and weak identity cleavages.


Objectives: The objective of present study aim towards promising potential of acyclovir containing Poly Lactic-Co-Glycolic Acid based nanoparticles for delivering drug to ocular cavity and could be view as alternative to conventional dosage form. Methods: The acyclovir containing Poly Lactic- Co-Glycolic Acid based polymeric nanoparticles were prepared by using nanoprecipitation technique and the optimized formulation was evaluated for particle size, encapsulation efficiency, in vitro release study, Differential Scanning Calorimetry, X-Ray Diffraction, Scanning Electron Microscopy, redispersibility, swelling index, ex vivo study and stability studies. Results: Among all the developed polymeric Nanoparticle formulations, optimized formulation (F1) showed Zeta Particle size 269 nm, Encapsulation Efficiency 90.1%. In vitro release studies exhibited 98.78% of drug release within 3 hr and ex-vivo studies indicate optimize formulation is nonirritant. Differential Scanning Calorimetry and X-Ray Diffraction indicate the optimized formulation show amorphous form. Scanning Electron Microscopy of optimized formulation show cylindrical in shape and their size was in the nanometer range. In terms of particle size, drug loading performance, redispersibility, in vitro release characteristics, sterility and better ocular tolerability, the formulated acyclovir nanoparticles were found to be a suitable and potential natural carrier. Suitable results have been shown in the stability study of acyclovir from nanoparticles. Conclusion: Therefore, the results concluded that Polymeric Nanoparticle could be considered as ocular delivery system for the prolong residence time of precorneal drug and increase penetration of corneal drug.


This paper introduces an approach for formally verifying the safety of the flight controller of an octorotor platform. Our method involves finding regions of the octorotor's state space that are considered safe, and which can be proven to be invariant with respect to the dynamics. Specifically, exponential barrier functions are used to construct candidate invariant regions near desired commanded states. The proof that these regions are invariant is discovered automatically using the dReal SMT solver, which ensures the accurate command tracking of the octorotor to within a certain margin of error. Rotor failures in which rotor thrusts become stuck at fixed values are considered and accounted for via a pseudo-inverse control allocator. The safety of the control allocator is verified in dReal by checking that the thrusts demanded by the allocator never exceed the capability of the rotors. We apply our approach on a specific octorotor example and verify the desired command tracking properties of the controller under normal conditions and various combinations of rotor failures.


Madura cattle breeding has long had a strategic role in supporting local economy. This study aimed to identify the profiles of beef cattle breeding based on local resources. Location of the studywas in Sumber Hasil farmer group, Talang Village, Seronggi Sub district, District of Sumenep Madura, East Java. The data collected were primary and secondary data and analyzed descriptively. Beef cattle breeding has been practiced using Madura cattle sincethe 1980's. Rearing system was intensive, in which the livestock were kept in the pen all the time with cut and carry feeding system. The feed offered consisted of elephant grass, field grass, seam grass, bamboo leaves, complete feed, and others. In addition, 3 kg of rice bran per head was provided on daily basis. Most of the cattle was kept in the pen/cages that belonged to the farmer, and the rest was kept in the communal cage belonged to the farmer group. Breeding system was mostly (97%) with natural mating and the rest with artificial insemination (AI). Service per conseption for the former was mostly one times (92.39%).Calving interval and anestrus post partus of  madura cows during the time between 2012 and 2014 was 13.49±3.10 months and 55.38±18.39 days, respectively.


Based on rapid improvements in digital mode with the extensive educational contents, the purpose and focus of this paper is to show off the digital collection for the use of Officer Trainees from Indian Civil Services and Civil Servants at different levels in India and in other democratic countries. An attempt has been made to present a case study of developing the digital preservations in the library of LBS National Academy of Administration, India. It will give a brief introduction of the issues which had been considered while setting up a digital project with C-DAC for changing the environment from physical to Digital. The project in Gyanlok section in Gandhi Smriti Library was a voluminously pains-taking and herculean task, which had to be completed with precision, accuracy and commitment to preserve the heritage and historical books in digital mode for the readers in perspective. In this paper, the author describes the work done within Gandhi Smriti Library, LBSNAA. Digital Preservation Group had created a list and description of the functional components of an ideal digital preservation environment for its library. The evolution of Digital environment is evidenced by developments in education & research, and growth of the literature & resources. Information Scientists' skills in surfing, collecting, organizing, evaluating information can contribute to develop a Model of Digital Preservations for the Academicians, Students, Trainees, Researchers, and Civil Servants.


Female mosquitoes use odor and heat as cues to navigate to a suitable landing site on their blood host. The way these cues affect flight behavior and modulate anemotactic responses, however, is poorly understood. We studied in-flight behavioral responses of females of the nocturnal malaria mosquito Anopheles gambiae sensu stricto to human odor and heat. Flight-path characteristics in a wind tunnel (flow 20 cm/s) were quantified in three dimensions. With wind as the only stimulus (control), short and close to straight upwind flights were recorded. With heat alone, flights were similarly short and direct. The presence of human odor, in contrast, caused prolonged and highly convoluted flight patterns. The combination of odor+heat resulted in longer flights with more landings on the source than to either cue alone. Flight speed was greatest (mean groundspeed 27.2 cm/s) for odor+heat. Odor alone resulted in decreased flight speed when mosquitoes arrived within 30 cm of the source whereas mosquitoes exposed to odor+heat maintained a high flight speed while flying in the odor plume, until they arrived within 15 cm of the source. Human odor evoked an increase in crosswind flights with an additive effect of heat at close range (<15 cm) to the source. This was found for both horizontal and vertical flight components. However, mosquitoes nevertheless made upwind progress when flying in the odor+heat generated plume, suggesting that mosquitoes scan their environment intensively while they progress upwind towards their host. These observations may help to improve the efficacy of trapping systems for malaria mosquitoes by (1) optimizing the site of odor release relative to trap entry and (2) adding a heat source which enhances a landing response.


Human mobility patterns can provide valuable information in understanding the impact of human behavioral regularities in urban systems, usually with a specific focus on traffic prediction, public health or urban planning. While existing studies on human movement have placed huge emphasis on spatial location to predict where people go next, the time dimension component is usually being treated with oversimplification or even being neglected. Time dimension is crucial to understanding and detecting human activity changes, which play a negative role in prediction and thus may affect the predictive accuracy. This study aims to predict human movement from a spatio-temporal perspective by taking into account the impact of activity changes. We analyze and define changes of human activity and propose an algorithm to detect such changes, based on which a Markov chain model is used to predict human movement. The Microsoft GeoLife dataset is used to test our methodology, and the data of two selected users is used to evaluate the performance of the prediction. We compare the predictive accuracy (R2) derived from the data with and without implementing the activity change detection. The results show that the R2 is improved from 0.295 to 0.762 for the user with obvious activity changes and from 0.965 to 0.971 for the user without obvious activity changes. The method proposed by this study improves the accuracy in analyzing and predicting human movement and lays the foundation for related urban studies.


Background: Opioid-induced adrenal insufficiency (OIAI) is reported in up to 29% of chronic opioid users through suppression of the hypothalamus-pituitary-adrenal axis. Unrecognized adrenal insufficiency leads to increased morbidity and potentially death; thus, healthcare provider (HCP) awareness of OIAI is crucial. Objective: To assess the knowledge and current practices of HCPs regarding OIAI and to identify factors associated with decreased awareness. Methods: Cross-sectional, anonymous survey of HCPs in internal medicine specialties that prescribe or care for patients taking chronic opioids. Results: Of 91 (30%) participants who completed the survey, 51 (56%) were men and 52 (57%) were in training. Most responders were general internal medicine providers (n=33, 36%), followed by endocrinologists (n=13, 14%) and various other specialties (n=45, 49%). While 61 (67%) of respondents prescribe opioids, only 17 (19%) were comfortable in their knowledge of opioid side effects. Among non-endocrine providers, 53 (68%) identified AI as known opioid-induced endocrinopathy. Compared to other providers, endocrinologists were more likely to recognize opioid-related endocrinopathies (69% vs 24%, P = 0.01) and identify the correct symptoms for OIAI (38% vs 9% P <0.001). One in 4 non-endocrine providers reported discomfort in managing glucocorticoid replacement therapy. The majority (60%) of providers indicated that online resources and CME lectures would improve knowledge of OIAI. Conclusions: Our study identified several deficiencies in HCP knowledge of opioid-induced endocrine effects, especially in non-endocrine providers. As many symptoms of OIAI overlap with those of underlying condition, OIAI could be potentially missed highlighting the need to further educate providers about opioid-induced endocrinopathies.


UNLABELLED
Phosphatidylinositide 3' (PI3')-lipid signaling cooperates with oncogenic BRAF(V600E) to promote melanomagenesis. Sustained PI3'-lipid production commonly occurs via silencing of the PI3'-lipid phosphatase PTEN or, less commonly, through mutational activation of PIK3CA, encoding the 110-kDa catalytic subunit of PI3'-kinase-α (PI3Kα). To define the PI3K catalytic isoform dependency of BRAF-mutated melanoma, we used pharmacologic, isoform-selective PI3K inhibitors in conjunction with melanoma-derived cell lines and genetically engineered mouse (GEM) models. Although BRAF(V600E)/PIK3CA(H1047R) melanomas were sensitive to the antiproliferative effects of selective PI3Kα blockade, inhibition of BRAF(V600E)/PTEN(Null) melanoma proliferation required combined blockade of PI3Kα, PI3Kδ, and PI3Kγ, and was insensitive to PI3Kβ blockade. In GEM models, isoform-selective PI3K inhibition elicited cytostatic effects, but significantly potentiated melanoma regression in response to BRAF(V600E) pathway-targeted inhibition. Interestingly, PI3K inhibition forestalled the onset of MEK inhibitor resistance in two independent GEM models of BRAF(V600E)-driven melanoma. These results suggest that combination therapy with PI3K inhibitors may be a useful strategy to extend the duration of clinical response of patients with BRAF-mutated melanoma to BRAF(V600E) pathway-targeted therapies.

SIGNIFICANCE
Although BRAF(V600E) pathway-targeted therapies elicit melanoma regression, the onset of drug resistance limits the durability of response. Here, we show that combined treatment with PI3K inhibitors significantly forestalled the onset of MEK1/2 inhibitor-resistant disease in BRAF-mutated GEM melanoma models. These results provide a conceptual framework for the combined deployment of BRAF(V600E) plus PI3K pathway-targeted inhibitors in the treatment of a subset of patients with BRAF-mutated melanoma.