Note: This document has been superseded by Guidelines to the international locational banking statistics and Guidelines to the international consolidated banking statistics This Guide to the international banking statistics is intended to serve two main purposes: firstly, to provide reporting countries with definitions and guidelines for the reporting of data; secondly, to give a detailed account of current country practices regarding the coverage and disaggregation of the reported data. The Guide describes two statistical systems, the locational banking statistics and the consolidated banking statistics. It replaces the previous issue (July 2000) and includes numerous changes and updates to the tables on countries' reporting practices. The locational banking statistics, which are described in Part I, gather quarterly data on international financial claims and liabilities of bank offices resident in the reporting countries broken down by currency, sector and country of residence of counterparty, and by nationality of reporting banks. In this system, both domestic and foreign-owned banking offices in the reporting countries record their positions on a gross (unconsolidated) basis, including those vis-ý-vis own affiliates, which is consistent with the principles of national accounts, balance of payments and external debt statistics. The statistics were introduced with a breakdown by major individual currencies and a partial sectoral and geographical breakdown at the beginning of the 1970s to provide information on the development and growth of the eurocurrency markets. In the subsequent years, the issue of recycling oil-related surpluses and the accompanying rise in international indebtedness shifted the emphasis in favour of a more detailed geographical breakdown and of flow data. The outbreak of the debt crisis in the early 1980s stimulated further efforts to refine both the geographical coverage of the data and the estimates of exchange rate adjusted flows. In the early 1990s, strong interest arose in making use of these statistics to improve the coverage and accuracy of the recording of balance of payments transactions. Following the financial crises in emerging economies in the late 1990s the locational banking statistics became an important component of the Joint BIS-IMF-OECD-World Bank Statistics on External Debt, which were developed in response to requests for dissemination of more timely external debt indicators. The consolidated banking statistics, which are described in Part II, collect quarterly data on banks' international financial claims broken down by remaining maturity and sector of borrower. In addition, they include information on exposures by country of immediate borrower and on the reallocation of claims (ie risk transfers) to the country of ultimate risk. The latter is defined as the country where the guarantor of a claim resides. The data mainly cover claims reported by domestic bank head offices, including the exposures of their foreign affiliates, and are collected on a worldwide consolidated basis with inter-office positions being netted out. The statistics also provide separate data on international claims of foreign bank offices whose head offices are located outside the reporting countries on an unconsolidated basis. The statistics were introduced as a semiannual reporting exercise in the late 1970s and early 1980s to provide information on the country risk exposures of major individual nationality banking groups to developing countries. Following the financial crises in emerging economies in the late 1990s, the consolidated banking statistics were enhanced to include complete country coverage of banks' on-balance sheet exposures, separate country data on an ultimate risk basis and a move to a quarterly reporting frequency. In response to recommendations of a working group of the CGFS, and in order to maintain the consolidated banking statistics as a key source of public information on international financial market developments, it is planned to improve the measurement of commercial banks' consolidated country risk exposures on an ultimate risk basis. Consequently, the statistics will, as from end-2004, cover more detailed and comprehensive data on country risk exposures inclusive of derivatives and other off-balance sheet positions. Part III of this Guide provides a glossary of terms used in the locational and consolidated banking statistics, while part IV contains a list of international organisations (Appendix 1) and official monetary authorities (Appendix 2). Beginning in 1998, the BIS has invited a number of additional countries, in particular from emerging markets, to participate in the international banking statistics. This is intended to further increase the global coverage of the statistics. So far, 12 economies have joined the locational (Australia, Bermuda, Brazil, Chile, Guernsey, India, Isle of Man, Jersey, Panama, Portugal, Taiwan (China) and Turkey) and nine have joined the consolidated (Brazil, Chile, Hong Kong, India, Panama, Portugal, Singapore, Taiwan (China), and Turkey) banking statistics, with more countries expected to be included in the near future. The Guide has been prepared with the assistance of the central banks or official authorities contributing to the two sets of international banking statistics. The BIS is grateful to all these institutions for their cooperation and valuable advice in its preparation. Note: This document supersedes "The Guide to the International Banking Statistics" (July 2000)


Avirulent Bacteria and parasites act as "tiny missile like carriers" capable to carry the magnetic nanoparticles (NMP) together with anticancer or radiosensitizer drugs at the tumor site. We compared the iron-oxide particles binding characteristics with nitroimidazole in monoaxenic avirulent E.histolytica NIH 200, Candida albicans and Salmonella BR 509 alongwith their membrane lipids and drug sensitivity. Major results were: 1. Microscopic experiments showed engulfed MNP particles passaged across the microbe membrane; 2.E.histolytica was oval shaped; Candida was thread like structure with capability of iron and manganese synthesis in situ; and Salmonella BR 509 was rod shaped 1 micron in size; 3. The nano-sized particles were diffused slowly into the cell membrane by stimulation of colony stimulating factor; 4.The nitroimidazole coated nanoparticles embedded in microbe membranes showed sequential reduction of gluconeogenesis and energy metabolic integrity loss in microbes due to their interaction with host tissue sites; 5.The MNP-loaded micro-organism showed slow drug delivery rate from micro-organisms dependent on size of nanoparticle, composition of microorganism membrane; 6. The comparison showed the nitroimidazole release rate was dependent on medium pH, temperature, nutrients used and colony stimulating factor in Candida > Salmonella > E.histolytica at temperature range of 41.5to 42.5˚C and magnetic field at 0.5-1 MHz;7. At high magnetic field, the microorganism cells showed necrosi s, loss of cell viability. In conclusion, the mechanism of nitroimidazole controlled release across microbial membrane depends on physiological pH, culture medium composition, nanoparticle size, colony stimulating factor, magnetic field and temperature. The mechanism of controlled drug delivery by avirulent micro-organisms has significance in designing a targeted anticancer drug therapy to focal tumors.


In this chapter, novel attack‐aware routing and wavelength assignment (Aa‐RWA) algo‐ rithms for multiperiod network planning are proposed. The considered physical layer attacks addressed in this chapter are high‐power jamming attacks. These attacks are modeled as interactions among lightpaths as a result of intra‐channel and/or inter‐chan‐ nel crosstalk. The proposed Aa‐RWA algorithm first solves the problem for given traffic demands, and subsequently, the algorithm is enhanced in order to deal with demands under uncertainties. The demand uncertainty is considered in order to provide a solu‐ tion for several periods, where the knowledge of demands for future periods can only be estimated. The objective of the Aa‐RWA algorithm is to minimize the impact of possible physical layer attacks and at the same time minimize the investment cost (in terms of switching equipment deployed) during the network planning phase.


Abstract A key limiting factor in organising and using information from physical specimens curated in natural science collections is making that information computable, with institutional digitization tending to focus more on imaging the specimens themselves than on efficiently capturing computable data about them. Label data are traditionally manually transcribed today with high cost and low throughput, rendering such a task constrained for many collection-holding institutions at current funding levels. We show how computer vision, optical character recognition, handwriting recognition, named entity recognition and language translation technologies can be implemented into canonical workflow component libraries with findable, accessible, interoperable, and reusable (FAIR) characteristics. These libraries are being developed in a cloud-based workflow platform—the 'Specimen Data Refinery' (SDR)—founded on Galaxy workflow engine, Common Workflow Language, Research Object Crates (RO-Crate) and WorkflowHub technologies. The SDR can be applied to specimens' labels and other artefacts, offering the prospect of greatly accelerated and more accurate data capture in computable form. Two kinds of FAIR Digital Objects (FDO) are created by packaging outputs of SDR workflows and workflow components as digital objects with metadata, a persistent identifier, and a specific type definition. The first kind of FDO are computable Digital Specimen (DS) objects that can be consumed/produced by workflows, and other applications. A single DS is the input data structure submitted to a workflow that is modified by each workflow component in turn to produce a refined DS at the end. The Specimen Data Refinery provides a library of such components that can be used individually, or in series. To cofunction, each library component describes the fields it requires from the DS and the fields it will in turn populate or enrich. The second kind of FDO, RO-Crates gather and archive the diverse set of digital and real-world resources, configurations, and actions (the provenance) contributing to a unit of research work, allowing that work to be faithfully recorded and reproduced. Here we describe the Specimen Data Refinery with its motivating requirements, focusing on what is essential in the creation of canonical workflow component libraries and its conformance with the requirements of an emerging FDO Core Specification being developed by the FDO Forum.


Many gaps remain in understanding fatigue across the phases of the cancer experience. These include determining the extent to which fatigue is a presenting or continuing symptom of cancer or a side effect of cancer treatment, identifying those at highest risk of fatigue, defining factors that differentiate between those who do and do not experience fatigue, and characterizing fatigue in special populations such as those with advanced cancer, children, and elders. This article reviews current knowledge of who experiences fatigue, the relationship of fatigue to cancer treatment, and the phenomenon of persistent fatigue following treatment. Critical elements in the research agenda that need to be addressed include the relationship of fatigue to other symptoms of cancer or side effects of treatment, mechanisms underlying fatigue and the development of mechanism-specific approaches to preventing and managing this troublesome symptom.


High volatility and enormous international capital flows are negative effects of the globalization of financial markets that can lead to financial crises like those of the 1990s. The Tobin tax often has been put forward as a measure to diminish globalization risks since it is claimed to discourage short-term speculation. The arguments of the proponents of this transactions tax are based on the assumption that (i) short-term trading is destabilizing and speculative and causes the volatility to increase, (ii) the Tobin tax does discourage this speculation and (iii) the Tobin tax causes market participants to orientate more by macroeconomic fundamentals. This paper suggests that these assumptions are quite questionable. Moreover, a Tobin tax of a sensible rate would be too small to protect countries from currency fires and would generate only little monetary autonomy. In addition to theoretical economic doubts there arise some political problems, which can make the tax to become infeasible.


[Extract] SUMMARY This study forms part of a wider research program investigating the risks to native fauna associated with the use of the second generation anticoagulant rodenticide Klerat® (0.005% brodifacoum active ingredient) in Queensland sugarcane fields. The study focuses on the five sugarcane growing areas where rodents are known to cause serious damage to crops and where Klerat® is currently or may potentially be used.

Seven of the nine species of owl which are found in Australia are known to occur within sugarcane growing areas in Queensland. A search of available literature and a lengthy consultation process with ornithologists throughout the state identified a general paucity of quantitative data relating to populations of owls in and around Queensland sugarcane growing areas apart from the Herbert River district where estimates of breeding populations of five species over the past 10 years are available. One known cause of mortality of owls in sugarcane growing areas is roadkill by collision with vehicles. One dead owl has been analysed for anticoagulant residues and was found to contain detectable levels of brodifacoum.

A number of factors were identified as potentially affecting owl populations in sugarcane growing areas and comprised: •extraordinary climatic events •fire •habitat change •human-related mortality •cane growing practices •immigration from other owl populations •mortality due to disease •agricultural practices in adjoining non-sugarcane crops •provision of owl nesting boxes •rodenticide use

The likely level of impact of each factor on owl populations in general during the study timeframe (past 25 years) was assessed. Two factors; changes to owl habitat and the use of rodenticides in sugarcane crops were identified as likely to have a high potential impact. All other factors were assessed as having a low impact apart from the effect of disease which was unable to be assessed due to a lack of available information.

The potential for secondary poisoning of owls from rodenticide use was reviewed in detail. It was concluded that there appears to be a significant potential for secondary poisoning of owls to occur in Queensland sugarcane as a result of the use of Klerat® due to the following factors: •even when Klerat® is applied at the recommended rate and using a pulse baiting technique there is the potential for high brodifacoum loadings in rodent prey to occur; •the consumption of bait does not appear to affect rodent behaviour, at least initially, therefore intoxicated rodents are probably as available to hunting owls as unaffected ones; •three species of owls are known to concentrate virtually all their hunting activity around sugarcane areas, and are selecting the same two rodent species as prey as are the targets of baiting campaigns; •four of the owl species are known to concentrate hunting effort in areas supporting large numbers of rodents and are therefore more likely to prey upon baited rodents as these areas will also attract baiting effort; and •four of the owl species concentrate their hunting effort around the margins of sugarcane blocks which is where the majority of bait is placed, particularly late in the growing season.

The Herbert River district was used as a case study for investigating the role of factors identified as potentially affecting owl populations in a substantial decline in owl numbers which has occurred in the district since 1992/93. It is likely that some, if not many of the factors listed above could have combined to Owl effect owl numbers during the decline period. However, many of these influences would have been occurring over a long time-frame and perhaps increasing their impact on owl populations gradually (e.g. road kills, habitat change) or only in the short term (e.g. disease, climate, emigration). Given the severity of the population decline observed (75-85% reduction in some species numbers), there must have been a few key factors that have created the impetus for this observed population crash. Two of these seem the most likely culprits: secondary poisoning from the introduction of Klerat® and the loss of habitat for breeding and foraging. Without further detailed information on past and present owl population numbers and data on the influence of habitat clearing and rodenticide introduction on these numbers, a definitive answer cannot be provided. However, the data presented in Young and De Lai (1997) presents a compelling case for the impact of secondary poisoning.

It was recommended that: information regarding the extent and type of natural habitats cleared for sugarcane in all districts under consideration should be obtained from the Department of Environment and the potential impact of habitat clearing on owl populations should be reviewed in light of this information; any further use of Klerat® and the potential impact of secondary poisoning on native fauna should be very closely monitored in the field on a small scale before its widespread introduction; and consideration be given to the use as an alternative in northern Queensland, other internationally accepted and low secondary poisoning risk rodenticides.


Climate change has become a key environmental narrative of the 21st century. However, emphasis on the science of climate change has overshadowed studies focusing on human interpretations of climate history, of adaptation and resilience, and of explorations of the institutions and cultural coping strategies that may have helped people adapt to climate changes in the past. Moreover, although the idea of climate change has been subject to considerable scrutiny by the physical sciences, recent climate scholarship has highlighted the need for a re‐examination of the cultural and spatial dimensions of climate, with contributions from the humanities and social sciences. Establishing a multidisciplinary dialogue and approach to climate research past, present, and future has arguably never been more important. This article outlines developments in historical climatology research and considers examples of integrated multidisciplinary approaches to climate, climatic variability, and climate change research, conducted across the physical sciences, social sciences, humanities, and the arts. We highlight the international Atmospheric Circulation Reconstructions over the Earth (ACRE) initiative as one example of such an integrated approach. Initially, ACRE began as a response from climate science to the needs of the agricultural sector in Queensland, Australia for a longer, more spatially, and temporally‐complete database of the weather. ACRE has now evolved to embrace an international group of researchers working together across disciplines to integrate their efforts into a four‐dimensional (4D) dynamical global historical climate‐quality reanalysis (reconstruction). WIREs Clim Change 2016, 7:164–174. doi: 10.1002/wcc.379


Country of Origin Labelling (COOL) regulation has been applied in the United States meat sector since October 2008. The industry must label beef, lamb and pork (ground meat and muscle cuts) sold through retail outlets according to its country of origin. The labelling requirements create differentiation at the retail level and may impose additional costs on producers, processors and retailers in the U.S. and elsewhere. The purpose of this analysis is to investigate whether there has been structural change in U.S. import demand for Canadian hog/pork products. Given that COOL has been in place for a limited period of time, we implement statistical procedures that are robust to structural change occurring at the end of the sample. We find evidence that COOL has impacted U.S./Canada slaughter hog trade flows. While Canadian feeder hog prices appear to have declined concurrently with the introduction of COOL, statistical hypothesis testing found little evidence of structural change for feeder hog trade flows that could be associated with COOL.


Moose browsing pressure in the vicinity of supplementary winter feeding stations eventually declines over time. It is believed that continual winter browsing over multiple years causes locally reduced shoot growth and forage availability for moose ( Alces alces ). We tested this hypothesis by comparing the size of annual shoots of Scots pine ( Pinus sylvestris ), downy birch ( Betula pubescens ), and Norway spruce ( Picea abies ) along a distance gradient from supplementary feeding stations. Contrary to our hypothesis, we found that shoot size was larger at feeding stations than at distances out to 1500 m. This increase in shoot size was probably not related directly to browsing, but to higher nutrient and light availability associated with moose activity at feeding stations. Increased use of Norway spruce, yet reduced browsing overall at feeding stations, probably reflects the overall decline in abundance of preferred Scots pine and downy birch in a local environment substantially altered by an artificially and abnormally high density of moose.


To reduce cost and ease maintenance, industrial control systems (ICS) have adopted Ethernetbased interconnections that integrate operational technology (OT) systems with information technology (IT) networks. This integration has made these critical systems vulnerable to attack. Security solutions tailored to ICS environments are an active area of research. Anomalybased network intrusion detection systems are well-suited for these environments. Often these systems must be optimized for their specific environment. In prior work, we introduced a method for assessing the impact of various anomaly-based network IDS settings on security. This paper reviews the experimental outcomes when we applied our method to a full-scale ICS test bed using actual attacks. Our method provides new and valuable data to operators enabling more informed decisions about IDS configurations.


With new design disciplines that challenge the borders of design practice and inquiry comes new possibilities for prototyping techniques and approaches. The basis for such an evolution is a firm understanding of the existing knowledge generated in design and the challenges posed by new design disciplines, such as service design. This study identifies a framework of perspectives for prototyping to reveal what the existing toolbox of prototyping contains based on a literature overview. Going through published literature from the early 1980s and onward, the framework is constructed using the following perspectives; purpose, fidelity, audience, position in the process, technique, and representation. These perspectives make knowledge about prototyping explicit and summarise contemporary approaches. Based on current challenges and characteristic attributes of service design the framework is then reconstructed to better cater to design for services. The conclusions are that validity and author are two perspectives that complement the existing framework, and that prototyping so far does not support a holistic approach to prototyping services.


Bipyridine glycoluril (BPG), a urea-fused bipyridine tecton, forms a square-pyramidal secondary building unit with copper(ii) which further self-assembles to give a porous hydrogen-bonded complex. This complex displays a high proton conductivity of 4.45 × 10-3 S cm-1 at 90 °C and 95% relative humidity (RH). Chains consisting of coordinated water, solvent water and nitrate anions embedded in the complex are responsible for high proton conduction. The proton conduction pathway was corroborated by ab initio electronic structure calculations with molecular dynamics (MD) simulations using the Nudged Elastic Band (NEB) method. The theoretical activation energy estimated to be 0.18 eV is in close agreement with the experimental value of 0.15 eV which evidences a Grotthuss proton hopping mechanism. We thus demonstrate that the hydrogen-bonded complex encapsulating appropriate counter ions, coordinated water and solvent water molecules exhibts superprotonic conductivity.


Introduction There is a notable absence of consensus on how to generate estimates ofpopulation-level incidence. Incidence is a considerably more sensitive and harder to estimate indicator of epidemiological trends than prevalence. We used a novel hybrid method to estimate HIV incidence by age and sex in a rural district of KwaZulu-Natal, South Africa. Methods Our novel method uses an 'optimal weighting' of estimates based on an implementation of a particular 'synthetic cohort' approach (interpreting the age/time structure of prevalence, in conjunction with estimates of excess mortality) and biomarkers of 'recent infection' (combining Lag-Avidity, Bio-Rad Avidity and viral load results to define recent infection, and adapting the method for age-specific incidence estimation). Data were obtained from a population-based cross-sectional HIV survey conducted in Mbongolwane and Eshowe health service areas in 2013. Results Using the combined method, we find that age-specific HIV incidence in females rose rapidly during adolescence, from 1.33 cases/100 person-years (95% CI:0.98,1.67) at age 15 to a peak of 5.01/100PY (4.14,5.87) at age 23. In males, incidence was lower, 0.34/100PY (0.00-0.74) at age 15, and rose later, peaking at 3.86/100PY(2.52-5.20) at age 30. Susceptible population-weighted average incidence in females aged 15-29 was estimated at 3.84/100PY (3.36-4.40), in males aged 15-29 at 1.28/100PY(0.68-1.50) and in all individuals aged 15-29 at 2.55/100PY (2.09-2.76). Using the conventional recency biomarker approach, we estimated HIV incidence among females aged 15-29 at 2.99/100PY (1.79-4.36), among males aged 15-29 at 0.87/100PY(0.22-1.60) and among all individuals aged 15-59 at 1.66/100PY (1.13-2.27). Discussion HIV incidence was very high in women aged 15-30, peaking in the early 20s. Men had lower incidence, which peaked at age 30. The estimates obtained from the hybrid method are more informative than those produced by conventional analysis of biomarker data, and represents a more optimal use of available data than either the age-continuous biomarker or synthetic cohort methods alone. The method is mainly useful at younger ages, where excess mortality is low and uncertainty in the synthetic cohort estimates is reasonably small. Conclusion Application of this method to large-scale population-based HIV prevalence surveys is likely to result in improved incidence surveillance over methods currently in wide use. Reasonably accurate and precise age-specific estimates of incidence are important to target better prevention, diagnosis and care strategies.


This paper presents the results of an investigation requested by the Multilateral Investment Fund of the Inter-American Development Bank under its Caribbean Microfinance Capacity Building project (CARIB-CAP) to strengthen microfinance in the English-speaking Caribbean. With the financial support of the Compete Caribbean program, this report seeks specifically to analyze the extent to which the regulation of financial entities in the region is supporting or inhibiting the development of microfinance in the region. Among the issues considered are the case for regulation, the differences between prudential and non-prudential regulation, the differences in regulatory arrangements among countries in the region, and especially the impact of these regulations on the availability of microfinancial services and on the different types of financial institutions that provide these services.


The discrete equations of motion derived using a variational principle are particularly attractive to be used in numerical optimal control methods. This is mainly because: i) they exhibit excellent energy behavior, ii) they extend gracefully to systems with holonomic constraints and iii) they admit compact representation of the discrete state space. In this paper we propose the use of sparse finite differencing techniques for the Discrete Mechanics and Optimal Control method. In particular we show how to efficiently construct estimates of the Jacobian and Hessian matrices when the dynamics of the optimal control problem is discretized using a variational integrator. To demonstrate the effectiveness of this scheme we solve a human motion planning problem of an industrial assembly task, modeled as a multibody system consisting of more than one hundred degrees of freedom.


Staphylococcus aureus is a Gram-positive bacterium that causes varieties of serious infections, and thus remains a significant threat to public health. The Mu50 glycopeptide-resistant S.aureus strain has reduced susceptibility to vancomycin, a glycopeptide antibiotic that is heavily relied on for the treatment of infections caused by S.aureus. The two component system GraSR genes from Mu50 glycopeptide-resistant S.aureus have been identified as a mediator in a rapid signal transduction cascade that occurs when the bacteria cell wall is stressed by antibiotics. Mu50 S.aureus, GraS and GraR were successfully cloned, expressed and purified using Glutathione Sepharose 4B for GraS which is designed for a single step purification of GST fusion protein, while GraR was purified using Fast Protein Liquid Chromatography with an anion exchanger resin DEAE Sepharose. The proteins are now ready for subsequent kinetics studies to investigate their role in cell wall stress by antibiotics, and regulation in cell wall biosynthesis. The Analysis of the Native Molecular Weight of the Citrate/Methylcitrate Synthase mmgD from strain 168" of Bacillus subtilis, a rod shape gram-positive bacterium, capable of forming endospore during inadequate supply of nutrients, and the mother cell metabolic gene (mmg) is one operon that is expressed during this sporulation. The mmgD protein is one of the six open reading frames (ORFs) of the mmg operon and was shown previously to be a combined citrate/methylcitrate synthase. The goal of this work was to determine the native molecular weight of this protein. Gel filtration chromatography is one of the methods use in determining the native state of a protein by comparing to known standard proteins molecular weights. The previously cloned mmgD gene was expressed, purified and subjected to gel filtration chromatography to establish its apparent native molecular weight. The analysis showed that a major fraction of the protein existed as a monomer while a very small fraction eluted from this column showed an aggregation of proteins.


We present an MPEG--7 compliant description of generic video sequences aiming at their scalable transmission and reconstruction. The proposed method allows efficient and flexible video coding while keeping the advantages of textual descriptions in database applications. Visual objects are described in terms of their shape, color, texture and motion; these features can be extracted automatically and are sufficient in a wide range of applications. To permit partial sequence reconstruction, at least one simple qualitative as well as a quantitative descriptor is provided for each feature. In addition, we propose a structure for the organization of the descriptors into objects and scenes and some possible applications for our method. Experimental results obtained with news and video surveillance sequences validate our method and highlight its main features.


Thioredoxin-1 (Trx1) is a thiol-disulfide oxidoreductase that can reduce transiently formed disulfide bonds in substrate proteins. The enzyme is released from lymphocytes and has extracellular cytokine-like actions, but the mechanisms by which it produces such effects are not known. Schwertassek et al. used a modified form of Trx1 in a substrate trapping assay (in which the engineered Trx1 formed long-lived mixed disulfide intermediates with its targets) to search for cell-surface proteins that might be modified by the enzyme. An affinity tag on the modified Trx1 allowed purification of the complexes and subsequent identification of associated proteins by mass spectrometry. In the human Epstein-Barr virus--transformed lymphoblastoid B cell line LCL-721.220--the authors found just one primary target of Trx-1, a member of the tumor necrosis factor receptor (TNFR) superfamily known as TNFRSF8 or CD30. The association of the proteins was lost under reducing conditions and, although all TNFR superfamily members characteristically have cysteine-rich domains, association with Trx1 was specific to CD30. Modification of CD30 appeared to cause a conformational change in the receptor because recognition of the receptor by antibodies was altered. This action of Trx1 required the presence of a source of reducing equivalents. Incubation of Hodgkin's lymphoma HDLM-2 cells decreased binding of recombinant soluble CD30 ligand to its receptor at the cell surface and, in the YT granular lymphoma cell line, blocked increased expression of the gene encoding the interleukin-2 receptor alpha chain, which is normally activated by CD30 signaling. The authors thus propose that excreted Trx1 may alter receptor function and may, in this way, link oxidative stress to lymphocyte function. U. Schwertassek, Y. Balmer, M. Gutscher, L. Weingarten, M. Preuss, J. Engelhard, M. Winkler, T. P. Dick, Selective redox regulation of cytokine receptor signaling by extracellular thioredoxin-1. EMBO J. 26, 3086-3097 (2007). [PubMed]


The cancer stem cell (CSC) hypothesis implicates the development of new therapeutic approaches to target the CSC population. Characterization of the pathways that regulate CSCs activity will facilitate the development of targeted therapies. We recently reported that the enzymatic activity of ALDH1, as measured by the ALDELFUOR assay, can be utilized to isolate normal and malignant breast stem cells in both primary tumors and cell lines. In this study, utilizing a tumorsphere assay, we have demonstrated the role of retinoid signaling in the regulation of breast CSCs self-renewal and differentiation. Utilizing the gene set enrichment analysis (GSEA) algorithm we identified gene sets and pathways associated with retinoid signaling. These pathways regulate breast CSCs biology and their inhibition may provide novel therapeutic approaches to target breast CSCs.


Estrone conjugate (E 1 C) and pregnanediol glucuronide (PdG) were predominant steroid metabolites of estrogen and progesterone in feces of most primates and could be used to evaluate ovarian function. These metabolites were determined along with records of genital swelling throughout 3-4 months period from three female Javan Gibbons (Hylobates moloch) maintained in pairing-typed cage at Schmutzer Primate Center, Jakarta (Ullah) and at Taman Margasatwa Taman Sari, Bandung (Donna and Citah). Following methanolic extraction of lyophilized fecal powder, samples were analyzed using enzyme linked immunosorbent assay (ELISA) for E 1 C and PdG. In all of the three females observed, both hormone profiles did not indicate any regular cycle of ovarian function even though genital swellings were sometimes observed. In one female (Donna) the hormone patterns showed clear signs of cycle irregularities with extended luteal phase of 40 days and erratic pattern of follicular phase. Of the other two females, no ovarian cycle was found. The data indicate that the fecal steroids analysis is a practical and valuable diagnostic tool for providing reliable information on ovarian function in Javan Gibbon. Factors affected reproductive hormonal profile should be taken in consideration in trying to achieve success in captive breeding program for this species.


This paper analyzes optimal portfolio decisions of long-horizon investors with undiversifiable labor income risk and exogenous expected retirement and lifetime horizons. It shows that the fraction of savings optimally invested in stocks is unambiguously larger for employed investors than for retired investors when labor income risk is uncorrelated with stock return risk. This result provides support for the popular recommendation by investment advisors that employed investors should invest in stocks a larger proportion of their savings than retired investors. This paper also examines the effect of increasing labor income risk on savings and portfolio choice and finds that, when labor income risk is independent of stock market risk, a mean-preserving increases in the variance of labor income growth increases the investor's willingness to save and reduce her willingness to hold the risky asset in her portfolio. A sensible calibration of the model shows that savings are relatively more responsive to changes in labor income risk than portfolio demands. Positive correlation between labor income innovations and unexpected asset returns also reduces the investor's willingness to hold the risky asset, because of its poor properties as a hedge against unexpected declines in labor income. This paper also provides intuition on the peculiar form of optimal portfolio choice of very young investors predicted by the standard life-cycle model.


It seems beyond bizarre to ask whether Justice Scalia had a theory of textual interpretation. If he did not have such a theory, what were he and his critics talking about for the past three decades? The answer is that they were talking about part of a theory of textual interpretation but not an actual, complete theory. A complete theory of textual interpretation must prescribe principles of admissibility (what counts towards meaning), significance (how much does the admissible evidence count), standards of proof (how much evidence do you need for a justified conclusion), burdens of proof (does inertia lie with acceptance or rejection of a proposed meaning), and closure (when is the evidence set adequate to justify a claim). Justice Scalia said a great deal about principles of admissibility and significance, but he said very little about the other essential elements of an interpretative theory. Moreover, much of what Justice Scalia said, and much else that can be inferred from his writings, about statutes and constitutions concerned theories of adjudication rather than theories of interpretation. The relationship between interpretation – the ascertainment of textual meaning – and adjudication – the determination of real-world cases – is actually quite complex, even if one has a normative theory of adjudication that says to decide cases as much as possible in accordance with interpretatively derived textual meaning. In the end, one probably cannot say that Justice Scalia had a theory of textual interpretation. He came close, however, to articulating a complete theory of how to apply statutes and constitutions in adjudication; he was lacking only a clear identification of the appropriate standard of proof for resolving legal claims in adjudication.


Background: Social media data is a promising source of social science data. However, deriving the demographic characteristics of users and dealing with the nonrandom, nonrepresentative populations from which they are drawn represent challenges for social scientists.

Objective: Given the growing use of social media data in social science research, this paper asks two questions: 1) To what extent are findings obtained with social media data generalizable to broader populations, and 2) what is the best practice for estimating demographic information from Twitter data?

Methods: Our analyses use information gathered from 979,992 geo-located Tweets sent by 22,356 unique users in South East England between 23 June and 4 July 2014. We estimate demographic characteristics of the Twitter users with the crowd-sourcing platform CrowdFlower and the image-recognition software Face++. To evaluate bias in the data, we run a series of log-linear models with offsets and calibrate the nonrepresentative sample of Twitter users with mid-year population estimates for South East England.

Results: CrowdFlower proves to be more accurate than Face++ for the measurement of age, whereas both tools are highly reliable for measuring the sex of Twitter users. The calibration exercise allows bias correction in the age-, sex-, and location-specific population counts obtained from the Twitter population by augmenting Twitter data with mid-year population estimates.

Contribution: The paper proposes best practices for estimating Twitter users' basic demographic characteristics and a calibration method to address the selection bias in the Twitter population, allowing researchers to generalize findings based on Twitter to the general population.


Background Gliomas are the most common primary brain tumours, accounting for 80% of malignant tumours of the central nervous system. Glioblastoma Multiforme (GBM), a grade IV glioma, is the most aggressive, with an overage overall survival (OS) of 12 months, and the most prevalent, about 60–70% of all gliomas. In recent years, chromosomal, genetic and epigenetic mutations in GBM have been discovered and are under investigation to determinate their role in clinical practice. Purpose To determine the main biomarkers evaluated for possible clinical utility in GBM. Materials and methods Literature review of biomarkers associated with treatment response/prognosis in GBM published in 2009 or later in a third or upper quartile in their category. Results Forty-two articles were reviewed. The main biomarkers identified in gliomas were: mutations involving isocitrate dehydrogenase, 1p/19q deletion status and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. Currently, MGMT status is the most acknowledged, being considered a predictive factor for chemotherapy response. The MGMT gene encodes an enzyme that repairs the damage induced by O(6)-alkylating agents, such as temozolomide, an oral chemotherapy drug indicated in primary GBM. About 50% of patients show this promoter methylated in tumoral cells, resulting in low expression of this enzyme. Several studies show higher OS and free survival progression (FSP) in patients with methylated promoter. Patients with unmethylated promoter present a response to radiotherapy plus temozolomide similar to radiotherapy alone, in terms of OS and FSP. The most accepted method of determining promoter status is polymerase chain reaction after extraction of DNA and sodium bisulphite conversion. Conclusions Biomarkers such as MGMT promoter methylation status could help therapeutic management of GBM patients. Although the role of MGMT promoter methylation status in GBM response to temozolomide is well known, it is not yet taken into account in clinical decision-taking. No conflict of interest.


Long non-coding RNAs (lncRNAs) have recently gained attention because of their regulatory roles on expression of genes involved in the immune response and cancer. In the present study, we evaluated expression of two lncRNAs (GSTT1-AS1 and IFNG-AS1) and their target genes (TNFA and IFNG) in human lung cancer samples and their adjacent non-cancerous tissues (ANCTs) to find their putative role in the pathogenesis of lung cancer. No significant difference was found in the expression of TNFA, IFNG, GSTT1-AS1 and IFNG-AS1 between tumoral and non-tumoral tissues. Expression levels of these genes were not associated with tumor stage after adjusting the effects of age. Moreover, expression levels of none of these genes were correlated with patients' age. However, significant pairwise correlations were detected between expressions of genes in both tumoral and non-tumoral tissues. TNFA, IFNG, GSTT1-AS1 and IFNG-AS1 are not possibly involved in the pathogenesis of lung cancer.


This thesis presents a number of methodological developments that were raised by a real life application to measuring the efficiency of bank branches. The advent of internet banking and phone banking is changing the role of bank branches from a predominantly transaction-based one to a sales-oriented role. This fact requires the development of new forms of assessing and comparing branches of a bank. In addition, performance assessment models must also take into account the fact that bank branches are service and for-profit organisations to which providing adequate service quality as well as being profitable are crucial objectives. This study analyses bank branches performance in their new roles in three different areas: their effectiveness in fostering the use of new transaction channels such as the internet and the telephone (transactional efficiency); their effectiveness in increasing sales and their customer base (operational efficiency); and their effectiveness in generating profits without compromising the quality of service (profit efficiency). The chosen methodology for the overall analysis is Data Envelopment Analysis (DEA). The application attempted here required some adaptations to existing DEA models and indeed some new models so that some specialities of our data could be handled. These concern the development of models that can account for negative data, the development of models to measure profit efficiency, and the development of models that yield production units with targets that are nearer to their observed levels than targets yielded by traditional DEA models. The application of the developed models to a sample of Portuguese bank branches allowed their classification according to the three performance dimensions (transactional, operational and profit efficiency). It also provided useful insights to bank managers regarding how bank branches compare between themselves in terms of their performance, and how, in general, the three performance dimensions are connected between themselves.


This paper summarizes the technical basis for the application of wetland protection regulatory schemes upon a number of typical environmental engineering and related projects. A number of scientifically recognized wetland values are outlined, since these from the basis for most regulatory controls and project permit strategies. Federal and state wetland regulatory programs are considered, with special focus upon the current status of the U. S. Army Corps of Engineers 404 permit program and Massachusetts Department of Environmental Quality Engineering regulations in relation to environmental engineering projects located in or adjacent to wetlands. (Author abstract. )


Vidy Bay is located near Lausanne on the northern shore of Lake Geneva in an area where sewage outfalls and drinking water intakes are positioned. Local circulation patterns may control water quality aspects in this part of lake. Currents are mainly influenced by variable wind regimes and the lake's thermal structure. Field experiments and numerical simulations were carried out to quantify the circulation patterns in this part of the lake. A set of Lagrangian drifters was used to capture current patterns and to measure air and water temperature and wind velocity in Vidy Bay. Current measurements were compared with simulations from a 3D hydrodynamic model (Delft3D-FLOW), covering all of Lake Geneva. Higher resolutions of bathymetry and grid mesh size were used for the Vidy Bay. Meteorological data for the model's surface boundary conditions were provided by the high-resolution (2.2 km gridded) MeteoSwiss COSMO-2 model. Modeled currents compared well with the field data. The validated model was used to identify typical current patterns in the bay. Consistent with previous observations of the bay's currents, the modeling results showed that Vidy currents are highly variable both spatially and temporally, although current patterns were found to be follow the forcing by the different wind regimes across the whole lake.


Kaduna Metropolis is the capital city of Kaduna State, Nigeria and comprises four local governments. It is experiencing rapid urbanization and its associated challenges, including management of municipal solid waste (MSW). Solid waste management is currently handled by government engaged contractors who are paid for their services from public funds. Such contractors operate around public land uses and major roads. Other areas of the metropolis are serviced by the informal sector. Since transfer stations, public waste bins and official waste dumps are not easily accessible to the populated, low income areas, the informal waste contractors readily dispose MSW in drains and streams leading to floods during the rainy season. Residents of such areas are at risk and lack the organization, funding and structure to mitigate and adapt to the situation. Recently, MSW has become a resource, an opportunity for the poor to earn a living. Non participation of communities in MSW management constitutes a challenge. This study examined the development of community participation in MSW management in Kaduna and recommends the way forward. Data for the study was collected through questionnaires, focus group interviews and field inspection of six locations of mostly low income and densely populated areas of Kaduna. An average 88% of these people want free solid waste management services, a difficult desire in view of the resultant zero cost recovery. The study recommends an integrated MSW management structure involving government waste contractors, the informal sector and the communities.


Working-class Appalachian women on the picket line, fighting for better working conditions. White women organizing against the racial integration of schools. Native American women struggling for Indian treaty rights. African American women in the Black Panther Party. What prompts these women to adopt political stances outside mainstream politics? How are these women changed by personal experiences of militancy and activism? Until recently, radical and militant activists have been viewed largely as male, while women have been assumed to be apolitical, more interested in domestic concerns and personal relationships than in public issues and political controversies. Despite evidence that women have been involved in a wide range of political activities, from revolutionary parties to racial hate groups, little attention has been paid to women's radical action. No Middle Ground brings together a wide variety of contributors to uncover women's roles in radical and militant movements. Examining women's radicalism in the United States from the 1950s through the 1990s, the volume details women's activism in both right-wing and left-wing movements, in feminist as well as anti-feminist groups, and in both movements supporting racial equality and those favoring race supremacism. The essays shed light on the conditions which encourage women's militancy, the issues around which women mobilize, how they organize, and what divides them in organizations. The essays and personal narratives in No Middle Ground advance our understanding of the gendered underpinnings of activism that occurs outside the "middle ground" of conventional electoral and pressure group politics. They suggest the significance of identity, consciousness, personal biography, and external context for understanding women's involvement with radical protest movements. No Middle Ground brings new insight into women's oppositional politics, as well as into our understandings of radical action.


In Carnal Appetites, Elspeth Probyn charts the explosion of interest in food - from the cults that spring up around celebrity chefs, to our love/hate relationship with fast food, our fetishization of food and sex, and the impact of our modes of consumption on our identities. 'You are what you eat' the saying goes, but is the tenet truer than ever? As the range of food options proliferates in the West, our food choices become inextricably linked with our lives and lifestyles. Probyn also tackles issues that trouble society, asking questions about the nature of appetite, desire, greed and pleasure, and shedding light on subjects including: fast food, vegetarianism, food sex, cannibalism, forced feeding, and fat politics.


APPOINTMENTAlmost 13 years after retiring from politics, the "unwild and uncrazy" Michael Wilson, the finance minister and then the international trade minister in the two majority governments of former conservative prime minister Brian Mulroney, was named ambassador to the United States, Canada's most important diplomatic posting.It was a critical choice by the newly appointed minority government of Prime Minister Stephen Harper in February 2006. Relations between Canada and the United States had deteriorated sharply under Harper's Liberal predecessors, Jean Chretien and Paul Martin, even though Martin had made improved relations a priority. Matters weren't helped by the fact that there hadn't been an effective, long-serving ambassador in Washington for a number of years. Frank McKenna, the former Liberal premier of New Brunswick, resigned after only 10 months in the position after Harper won the election of 23 January. Former Deputy Prime Minister John Manley, like McKenna a Liberal leadership candidate who ultimately decided not to run, had been offered the embassy under Martin but declined.Given the offer to Manley and the appointment of McKenna, it was hardly a surprise that the embassy was offered to another politician, rather than to a diplomat. And that, according to one well-placed source, was not a bad thing: "Washington is the last place you need a traditional diplomat. Canada needs a decision-maker like Wilson who understands politics in Washington."Nor was it a surprise-though a tribute to the confidence that Harper had in Wilson-that the politician chosen was from the old Progressive Conservative side of the party, and had been a senior minister under Mulroney. After all, influential figures of that era, including Marjory LeBreton, Hugh Segal, and Derek Burney-himself a former ambassador to the United States-played roles during the campaign. In fact, Burney is thought to have helped persuade Harper to appoint Wilson (in an interview, Burney praised the appointment of "my old friend and colleague," but declined to discuss his role in the choice). Contributing to the appointment was the fact that the former finance minister had been co-chair of the Ontario campaign and had shared platforms with Harper, who joked that he had learned his charisma from Wilson.Whatever the politics, the appointment was widely praised in the press-The Economist called it "shrewd"-and by decision-makers. Every one of the 15 or so figures (including Liberals such as Roy MacLaren and Patrick Gossage) interviewed for this article had positive things to say about Wilson (a spokesperson for the embassy said that Wilson was declining interview requests).The Toronto native was variously described as highly experienced, a man of integrity and presence, dogged and determined, knowledgeable both about business and politics, exceptionally hard-working, and, most importantly, a person with direct access to the prime minister. "Diplomats are paid to lie for their country," mused Hugh Segal, a former Mulroney chief of staff and now a senator. "Michael is not a guy for whom lying, even in its lightest sense, is easily embraced.""It's hard not to look at his resume and say, it's our lucky day," commented Pamela Wallin, consul-general in New York. Added Richard Remillard, his press secretary from 1984 to 1990, "He's so formidable because behind that quiet, silent exterior, there is a real core of steel."While that core of steel will be essential in negotiating with the notoriously hard-nosed Americans, Allan Gotlieb, who was the ambassador from 1981 to 1989, points out that the real question is how tough an ambassador can be with his or her own government when it is wrong on an issue and needs to be told to back off."If you are popular in Ottawa, maybe you are not doing your job," he said. Fortunately, he continued, "Michael Wilson is not worried about popularity, and he is not running for anything. …


Enterprises increasingly rely on structured datasets to run their businesses. These datasets take a variety of forms, such as structured files, databases, spreadsheets, or even services that provide access to the data. The datasets often reside in different storage systems, may vary in their formats, may change every day. In this paper, we present GOODS, a project to rethink how we organize structured datasets at scale, in a setting where teams use diverse and often idiosyncratic ways to produce the datasets and where there is no centralized system for storing and querying them. GOODS extracts metadata ranging from salient information about each dataset (owners, timestamps, schema) to relationships among datasets, such as similarity and provenance. It then exposes this metadata through services that allow engineers to find datasets within the company, to monitor datasets, to annotate them in order to enable others to use their datasets, and to analyze relationships between them. We discuss the technical challenges that we had to overcome in order to crawl and infer the metadata for billions of datasets, to maintain the consistency of our metadata catalog at scale, and to expose the metadata to users. We believe that many of the lessons that we learned are applicable to building large-scale enterprise-level data-management systems in general.


In this paper we discuss topological BF theories in 3 and 4 dimensions. Observables are associated to ordinary knots and links (in 3 dimensions) and to 2‐knots (in 4 dimensions). The vacuum expectation values of such observables give a wide range of invariants. Here we consider mainly the 3 dimensional case, where these invariants include Alexander polynomials, HOMFLY polynomials and Kontsevich integrals.


Chronic malaria shortens telomeres Chronic infections are assumed to cause little damage to the host, but is this true? Migrant birds can pick up various species of malaria parasite while overwintering in the tropics. After initial acute malaria, migrant great reed warblers, which nest in Sweden and overwinter in Africa, are asymptomatically infected for life. Asghar et al. discovered that these cryptically infected birds laid fewer eggs and were less successful at rearing healthy offspring than uninfected birds. Furthermore, infected birds had significantly shorter telomeres (the protective caps on the ends of chromosomes) and produced chicks with shortened telomeres. Science, this issue p. 436 Chronic asymptomatic infection correlates with reduced breeding success and shortened telomeres in great reed warblers. Recovery from infection is not always complete, and mild chronic infection may persist. Although the direct costs of such infections are apparently small, the potential for any long-term effects on Darwinian fitness is poorly understood. In a wild population of great reed warblers, we found that low-level chronic malaria infection reduced life span as well as the lifetime number and quality of offspring. These delayed fitness effects of malaria appear to be mediated by telomere degradation, a result supported by controlled infection experiments on birds in captivity. The results of this study imply that chronic infection may be causing a series of small adverse effects that accumulate and eventually impair phenotypic quality and Darwinian fitness.


Social networks allow users getting personalized recommendations for interesting resources like websites or scientific papers by using reviews of users they trust. Search engines rank documents by using the reference structure to compute a visibility for each document with reference structure-based functions like PageRank. Personalized document visibilities can be computed by integrating both approaches. We present a framework for incorporating the information from both networks, and ranking algorithms using this information for personalized recommendations. Because the computation of document visibilities is costly and therefore cannot be done in runtime, i.e., when a user searches a document repository, we pay special attention to develop algorithms providing an efficient calculation of personalized visibilities at query time based on precalculated global visibilities. The presented ranking algorithms are evaluated by a simulation study.


In an effort to better assess the impact of future timber harvest on wildlife, and to develop pertinent recovery plans for endangered species in specific locations, habitat queries (searches to retrieve data from a vegetation database) may be used to identify polygons (homogenous areas for specific forest stand characteristics) used by a species. During the late winters of 2009, 2011 and 2012, I developed and tested queries to predict the distribution of Boreal Woodland Caribou (Rangifer tarandus caribou) habitat in Mistik Forest Management Agreement (FMA) area, in northwestern Saskatchewan. The objectives of this study were to 1) identify polygons with late-winter habitat potential according to forest stand composition and structural characteristics, 2) verify habitat use by Woodland Caribou, and 3) identify stands that should be protected in the future. In 2009, with a query based on generalities taken from Woodland Caribou habitat studies conducted in areas other than the Mistik FMA area, only 25% of track encounters (n = 8) occurred in polygons judged to be suitable for Woodland Caribou. After modifying the original query to include muskegs (treed bogs, treed fens, and treed swamps) that were ≤2 km apart, and upland stands that were ≤2 km from these muskegs, 76% and 93% of track encounters occurred in suitable polygons in 2011 (n = 46) and 2012 (n = 45), respectively. As predicted, the majority (61.5%) of 91 track encounters (≤2 Woodland Caribou/track encounter in most cases) occurred in muskegs, and nearly 25% were in late-successional, upland deciduous and mixed coniferous-deciduous stands located within 2 km from the edge of muskegs. Track encounters were significantly more frequent than expected in muskegs ( P 40% canopy closure with 0-10 m-high trees. There were no track encounters in Black Spruce ( Picea mariana) stands with 0-40% canopy closure and 0-20 m-high trees, and in Jack Pine (Pinus banksiana) pure or mixed coniferous stands. Track encounters were significantly less frequent than expected ( P<0.01) in deciduous stands. In muskeg habitats used by Woodland Caribou, there was 1 track encounter/246 m of transect in 2011, and 1 track encounter/264 m of transect in 2012. Woodland Caribou track encounters were recorded at the beginning of transects, beside active roads and on pipelines, or further away depending on the distance of transects from roads and suitable muskeg habitat. The findings of this study led to a more effective rating of forest stands to predict the late-winter distribution of Boreal Woodland Caribou in Mistik FMA area. The index of track encounters/km of suitable muskeg habitat may be useful to assess the persistence of the Woodland Caribou population over time.


Bevacizumab, an antibody against vascular endothelial growth factor (VEGF), is a promising, yet controversial, drug in human glioblastoma treatment (GBM). Its effects on tumor burden, recurrence, and vascular physiology are unclear. We therefore determined the tumor response to bevacizumab at the phenotypic, physiological, and molecular level in a clinically relevant intracranial GBM xenograft model derived from patient tumor spheroids. Using anatomical and physiological magnetic resonance imaging (MRI), we show that bevacizumab causes a strong decrease in contrast enhancement while having only a marginal effect on tumor growth. Interestingly, dynamic contrast-enhanced MRI revealed a significant reduction of the vascular supply, as evidenced by a decrease in intratumoral blood flow and volume and, at the morphological level, by a strong reduction of large- and medium-sized blood vessels. Electron microscopy revealed fewer mitochondria in the treated tumor cells. Importantly, this was accompanied by a 68% increase in infiltrating tumor cells in the brain parenchyma. At the molecular level we observed an increase in lactate and alanine metabolites, together with an induction of hypoxia-inducible factor 1α and an activation of the phosphatidyl-inositol-3-kinase pathway. These data strongly suggest that vascular remodeling induced by anti-VEGF treatment leads to a more hypoxic tumor microenvironment. This favors a metabolic change in the tumor cells toward glycolysis, which leads to enhanced tumor cell invasion into the normal brain. The present work underlines the need to combine anti-angiogenic treatment in GBMs with drugs targeting specific signaling or metabolic pathways linked to the glycolytic phenotype.


Protein kinases play a critical role in a wide variety of cellular processes through post-translational protein phosphorylation and identification of their substrate proteins is important for understanding the enzymes' mechanism of action and elucidating their functions in physiological and disease processes. However, there have been few systematic investigations of protein kinase substrates due to a lack of high-throughput kinetic assays. Thus, we designed an on-chip protein kinase assay for profiling kinase kinetic parameters by introducing the phosphorylation rate (Vp) under physiological conditions, instead of the maximal velocity (Vmax), in a high-throughput manner. We applied this method to the kinetic analysis of protein kinase A (PKA) for 28 nuclear, cytosolic, plasma membrane, and extracellular target proteins to determine the substrate affinity (Km), Vp (FIATP10/s), and substrate preference (Vp/Km). We then constructed a map of PKA's kinetic parameters with respect to the 28 proteins based on subcellular localization. Thus, the on-chip protein kinase kinetic profiling is an ideal approach for systematically investigating substrate proteins of protein kinases and fully characterizing the enzymes' physiological functions.


Problem Solving with C++ is intended for use in the C++ introductory programming course. Created for the beginner, it is also suitable for readers interested in learning the C++ programming language. Problem Solving with C++ continues to be the most widely used textbook by students and instructors in the introduction to programming and C++ language course. Through each edition, hundreds and thousands of students have valued Walt Savitchs approach to programming, which emphasizes active reading through the use of well-placed examples and self-test examples. Created for the beginner, this book focuses on cultivating strong problem-solving and programming techniques while introducing students to the C++ programming language. MyProgrammingLab for Problem Solving with C++ is a total learning package. MyProgrammingLab is an online homework, tutorial, and assessment program that truly engages students in learning. It helps students better prepare for class, quizzes, and examsresulting in better performance in the courseand provides educators a dynamic set of tools for gauging individual and class progress. Teaching and Learning Experience This program presents a better teaching and learning experiencefor you and your students. Personalized Learning with MyProgrammingLab: Through the power of practice and immediate personalized feedback, MyProgrammingLab helps students fully grasp the logic, semantics, and syntax of programming. Keep Your Course Current: This edition features a new introduction to C++11 in the context of C++98. Flexible Coverage that Fits your Course: Instructors can easily adapt the order in which chapters and sections are covered in their course without losing continuity. Clear and Friendly Presentation: Savitchs clear, concise style is a hallmark feature of the text, receiving praise from students and instructors alike. Tried-and-true Pedagogy: A suite of pedagogical tools, enhanced by understandable language and code, has been used by hundreds of thousands of students and instructors. Note: You are purchasing a standalone product; MyProgrammingLab does not come packaged with this content. If you would like to purchase both the physical text and MyProgrammingLab search for ISBN-10: 0133862216/ISBN-13: 9780133862218. That package includes ISBN-10: 0133591743/ISBN-13: 9780133591743 and ISBN-10: 0133834417 /ISBN-13: 9780133834413. MyProgrammingLab is not a self-paced technology and should only be purchased when required by an instructor.


In engineering practice, security incident in real terms is a gray system, so it is possible to predict the accident using gray system theory. In this article, we established the prediction model for pit deformation based on gray system theory, and predicted the pit deformation in future adopting actual project monitoring data. The results are in good agreement with the measured values, indicating the prediction model has good accuracy and has positive significance in guiding informationizaton construction of excavation engineering. We establish the metabolism model to improve the accuracy of the prediction model. Practice has shown that the accuracy of the metabolism model is higher than that of the old information model; the predicted results are consistent with the measured data


We carried out survey in a total 16 villages locating in and around the different protected areas in Nagaland. Out of 265 respondent 69 (28.2%) respondents confirmed the presence of sun bear by direct sighting and indirect evidences in 2 PAs of Nagaland. Overall status of sun bear was found to be low and rare in and around Pas. In the Nagaland states, human population is constantly on the increase and as a result, there are increasing biotic pressure on protected areas and reserve forests. The potential tropical rainforest habitats of sun bear should be well protected and management action for improvement these habitats should be taken up on priority. Livestock grazing should be restricted in forest areas. Presence of sun bears has been confirmed in the Itanki and Fakim National Parks of Nagaland, but it showed patchy distribution. Both direct and indirect evidences (scats, claw marks and foot prints) of sun bears were observed by inhabitants of these areas. Sun bears were reported to be sighted and indirect evidences were seen by inhabitants of villages.Public education and awareness programmes towards conservation and natural history of sun bear must be initiated by the forest department. Study on ecology and management of sun bear is also very necessary for formulation of action plan for mitigation of human-sun bear conflict and long term conservation of the species.


The Amen Anti-Addiction Intervention (AAI) is
an austere regimen intended to eradicate addictive impulses and behaviors. The
theoretical and empirical foundations of this intervention are explicated
herein. The AAI entails daily cyclic fasting, chronic caloric restriction,
supplementation with specific neutraceutical agents, rigorous exercise, and
minimalist meditation. The physiological focus of the AAI is twofold: the
augmentation of neurogenesis in a manner analogous to the effect of
psychotropic drugs and the activation of areas in the brain involved in the
regulation of emotional arousal and reward. The psychological focus of the AAI
is similarly twofold: the attenuation of anxiety and/or impulsivity and the
cultivation of mental mastery and/or self-control. It shall be argued that the
AAI, by virtue of its explicit integration of biological, psychological, and
sociological elements—each of which evidently influences addiction—will
plausibly be an improvement over existing interventions aimed at the treatment
of addiction.


Watersheds are physical regions from which all arriving water flows to a single exit point. The shared hydrology means that other biophysical systems are linked, typically with upper-gradient regions influencing lower-gradient ones. This situation frames the challenge of managing economic and other uses of watersheds both in terms of individual activities and their influence on other connected processes and activities. Economics provides concepts and methods that help managers with decision making in the complex physical, biological, and institutional environment of a watershed. Among the important concepts and methods that help characterize watershed processes are externalities, impacts of economic activity that fall upon individuals not party to the activity, and third parties, individuals impacted without consent. Public goods and common pool resources describe categories of things or processes that by their nature are not amenable to regular market transactions. Their regulation requires special consideration and alternative approaches to markets. Benefit-cost analysis and valuation are related methods that provide a means to compare alternative uses of the same system. Each is based on the normative argument that the best use provides the greatest net benefits to society. And intergenerational equity is a value orientation that argues for preservation of watershed processes for the benefit of future generations. The need for effective watershed management methods pushed 20th-century economists to adapt their discipline to the complexity of watersheds, from which emerged subdisciplines of natural resource economics, environmental economics, and ecological economics. The field is still evolving with a growing interest in data gathering through land-based low-cost data collection systems and remote sensing, and in emerging data analysis techniques to improve management decisions.


In international climate change negotiations, China's role is an issue of perennial concern. In particular, the lack of quantitative, absolute emissions commitments from China has often been the focus of this concern. In line with changing domestic and international contexts, China is recalibrating its stance and strategy. Its participation in international climate change negotiations has evolved from playing a peripheral role to gradually moving to the center. This article examines China's stance and role in international climate change negotiations from a historical perspective. In so doing, the article discusses the evolution of international climate negotiations and China's stance in the lead‐up to and at the Paris conference. With Paris behind us, the focus is now turning to the implementation of the Paris Agreement. The article discusses post‐Paris focuses, generally in the international context and in particular in China's context. They both affect the outcomes of post Paris subsequent negotiations and hold the key to actually achieving desired outcomes. WIREs Clim Change 2017, 8:e443. doi: 10.1002/wcc.443


This paper examines conflict management and resolution, focusing specifically on the Dayak Iban society of
Sarawak. It argues that conflicts can be substantially reduced if people are socialized to accept their
respective roles in the socioeconomic and political structure of society. Conflicts among the communal Ibans
are kept to a bare minimum because their sociocultural values promote harmonious interdependence among
individuals. Those who transgress the community accepted norms of behaviour are quickly ostracized,
reprimanded and made to feel greatly ashamed. Iban acceptance of their positions and roles within the
social, economic and political structure of society has helped to maintain social harmony, economic justice
and political stability. On a higher order, that is in Malaysian society, it is the realization of this sense of
justice that made the NEP acceptable and successful in allocating the benefits of economic growth among the
various ethnic groups in the country. In other words, each community according to its needs as seen by
political leaders.


In Re: Defining Securitization, Professor Jonathan Lipson attempts to define a "true" securitization transaction. My article engages Lipson's, exploring how securitization should be legally defined. As a starting point, even a normative approach to defining a financial concept should be pragmatic, taking into account how the concept is used in the real world. The definition also should take into account dynamically changing financial markets and, in what I call an audience-adaptive approach, the different perspectives of policymakers and lawmakers, market participants and their lawyers, regulators and judges, and other members of the "audience" affected by the definition.


The possibility of combining both the advantages of a solar tower thermal power plant and of a solar parabolic trough power plant could be interesting from an energetic point of view as well from an economic point of view. The preliminary study of this combination feasibility is the goal of this project. The study of the project viability consist first of all on the modeling of the trough system, the energy balance of the parabolic troughs will be established at first. Secondly, and choosing a perfect solar day simulating a day when the solar radiation is rather stable, with no cloudy periods along the day, the power available from the trough plant can be calculated. Once we have estimated the power that we can introduce into the cycle of the tower plant, the main issue consists on how and where it is better to use this energy in the cycle. Several possibilities seem to be interesting a priori, however a more detailed study of each one is to be done in order to get to the most economic and efficient layout. The work related to the tower thermal power plant will be done taking as starting point the master thesis of James Spelling, who did an incredible work in this field and whose work will be a valuable help to continue the research on the proposed concept in this project of combining two plants, tower and trough. The main advantage of the tower design compared to the parabolic trough design is the higher temperature. As it will be explained further, thermal energy at higher temperature can be converted more efficiently, the exergy efficiency is better. In terms of storage, the high temperature results in a cheaper and a more efficient storage system. Nevertheless, the set up of the field of heliostats is more complex than the set up of the parabolic trough lines even though the area for a trough plant must be previously flattened. The lower temperature level that entails an inconvenient itself for a parabolic trough power plant may become an advantage when combining both types of concentrating solar power plants. If the results are positive enough that it seems interesting to combine both types of power plants, another step forward will be done towards the use of the sun energy as a renewable source thus making it a more interesting choice for power generation. Sun potential has already shown as an important technology not only at the present time but also in the future. Commercial solar plants have already achieved levelized energy costs around 12-15 UScts/kWh, and the potential for cost reduction is expected to follow this trend even further, to costs as low as 5 UScts/kWh. In addition the taxes imposed for the non-green power should make even more interesting the use of concentrating solar power plants. The requirements of high beam normal radiation lead to a limited amount of suitable places where the implantation of this technology is possible. However many places exist on Earth where the conditions are perfectly adapted, we talk about regions such as United States (the country with more carbon dioxide emissions in the world), some regions in Mexico, North Africa, India, Australia, northeastern Brazil and some locations around the Mediterranean, especially in the south of Spain. The challenge is therefore set for a change in our energy production scheme.


This article presents a classifi cation of tamgas on petroglyphs and portable items. Tamgas are signs of group identity used by medieval Turkic nomads inhabiting Southern Siberia, Mongolia, and Kazakhstan. We describe eight groups of tamgas found in the Altai and in Semirechye, and compare them with similar signs from other parts of the region. The mapping of tamgas, including petroglyphic, sphragistic, and others allowed us to assess their date, ethno-political attribution, and migration routes of groups with which they were associated. The comparison of tamgas in the Altai and Semirechye evidences close links between those regions. Whereas certain groups of tamgas (combinations of many varieties) were emblems of major tribal unions, others were supratribal markers of social status, privileged clans, and alliances. Certain emblems were dynastic signs of the ruling elite. Dynastic tamgas of the Yaglakar clan are known from sites such as Syrnakh-Gozy and Kuray I in the Altai. Certain tamgas on coins and petroglyphs in Semirechye are emblems of the 8th and 9th century Karluk rulers of the Altai (Chagyn, Taldura, etc.) and central Mongolia (Shivet ulan). Two groups of tamgas (No. 1 and 3) have many derivatives, marking certain divisions of the Karluk federation. An example of a supratribal emblem is tamga No. 2, which shows little variation despite being found in various contexts across a vast territory.


Does the pattern of social connections between individuals matter for macroeconomic outcomes? If so, where do differences in these patterns come from and how large are their effects? Using network analysis tools, we explore how different social network structures affect technology diffusion and thereby a country's rate of growth. The correlation between high-diffusion networks and income is strongly positive. But when we use a model to isolate the effect of a change in social networks on growth, the effect can be positive, negative, or zero. The reason is that networks diffuse both ideas and disease. Low-diffusion networks have evolved in countries where disease is prevalent because limited connectivity protects residents from epidemics. But a low-diffusion network in a low-disease environment compromises the diffusion of good ideas. In general, social networks have evolved to fit their economic and epidemiological environment. Trying to change networks in one country to mimic those in a higher-income country may well be counterproductive.


This paper describes a model for a robot to appropriately control its position when it presents information to a user. This capability is indispensable since in the future many robots will be functioning in daily situations as shopkeepers presenting products to customers or museum guides presenting information to visitors. Psychology research suggests that people adjust their positions to establish a joint view toward a target object. Similarly, when a robot presents an object, it should stand at an appropriate position that considers the positions of both the listener and the object to optimize the listener's field of view and to establish a joint view. We observed human-human interaction situations where people presented objects and developed a model for an information-presenting robot to appropriately adjust its position. Our model consists of four constraints for establishing O-space: (1) proximity to listener, (2) proximity to object, (3) listener's field of view, and (4) presenter's field of view. We also present an experimental evaluation of the effectiveness of our model.


Background : Given the longevity achievable with current prophylactic and therapeutic strategies for persons with HIV infection, quality of life (QOL) has emerged as a significant medical outcome measure, and its enhancement has an important goal. This review highlights the relevance and complexity of physical, psychological, and social factors as determinants of health-related quality of life in HIV-infected person in Bushehr province. Methods : This cross-sectional study was conducted using a convenience sampling method on 54 patients living with HIV or suffering from AIDS on 2009. The method of data collection was summarized questionnaire of World Health Organization (WHO-QOL-Brief). The main measured outcome in this study was quality of life and some related demographic and clinical variables. Results : The majority of the patients were males (46/54) and unemployed (37).25 participants were married. The mean±SD age of the patients was 38.1±7.47 years. Employment, marital status, level of education, and clinical stage of the disease, had a significant effect on the quality of life of the patients. In multivariate analysis, the most important predictor of the quality of life was job. Conclusion: The most important factors, association with decreased quality of life of the Patients in this study, were being separated or divorced, unemployment and being at severe stage of the disease. The relationship of these measures to treatment outcomes can and should be examined in clinical settings in resource-limited countries.


Significance We identify the abundant presence in the human brain of magnetite nanoparticles that match precisely the high-temperature magnetite nanospheres, formed by combustion and/or friction-derived heating, which are prolific in urban, airborne particulate matter (PM). Because many of the airborne magnetite pollution particles are <200 nm in diameter, they can enter the brain directly through the olfactory nerve and by crossing the damaged olfactory unit. This discovery is important because nanoscale magnetite can respond to external magnetic fields, and is toxic to the brain, being implicated in production of damaging reactive oxygen species (ROS). Because enhanced ROS production is causally linked to neurodegenerative diseases such as Alzheimer's disease, exposure to such airborne PM-derived magnetite nanoparticles might need to be examined as a possible hazard to human health. Biologically formed nanoparticles of the strongly magnetic mineral, magnetite, were first detected in the human brain over 20 y ago [Kirschvink JL, Kobayashi-Kirschvink A, Woodford BJ (1992) Proc Natl Acad Sci USA 89(16):7683–7687]. Magnetite can have potentially large impacts on the brain due to its unique combination of redox activity, surface charge, and strongly magnetic behavior. We used magnetic analyses and electron microscopy to identify the abundant presence in the brain of magnetite nanoparticles that are consistent with high-temperature formation, suggesting, therefore, an external, not internal, source. Comprising a separate nanoparticle population from the euhedral particles ascribed to endogenous sources, these brain magnetites are often found with other transition metal nanoparticles, and they display rounded crystal morphologies and fused surface textures, reflecting crystallization upon cooling from an initially heated, iron-bearing source material. Such high-temperature magnetite nanospheres are ubiquitous and abundant in airborne particulate matter pollution. They arise as combustion-derived, iron-rich particles, often associated with other transition metal particles, which condense and/or oxidize upon airborne release. Those magnetite pollutant particles which are <∼200 nm in diameter can enter the brain directly via the olfactory bulb. Their presence proves that externally sourced iron-bearing nanoparticles, rather than their soluble compounds, can be transported directly into the brain, where they may pose hazard to human health.


Lorna Martin's life is in chaos and she needs to make some big changes. After all, there must be a reason she keeps chasing after the wrong men, making toe-curling blunders at work and generally failing to keep her life on track. Egged on by her friends, she signs up for the talking cure: a year of therapy with the frosty Dr J. Along the way, she catches sight of the holy grail of true love in the shape of the gorgeous Dr McDreamy. But will Lorna find her own happy ending? With support (and not a little exasperation) from her friends and long-suffering sister, some serious setting-the-world-to-rights sessions involving too many bottles of wine, and the help of her inscrutable shrink, Lorna feels she might be getting her life together. Revealing, intimate and highly entertaining, Woman on the Verge of a Nervous Breakdown is a must-read for any woman who loves the idea of being in love and worries about settling for second best.


AIM
It is still debated as to whether rhythmic gymnastics is a discipline at risk of low back pain, because the concern for the extreme and repetitive hyperextension of the column may be counteracted by protective factors which are distinctive of rhythmic gymnasts, namely: leanness, lumbar flexibility and muscle strength. This study aimed to assess the prevalence of low back pain in a cohort of former elite-level rhythmic gymnasts of the Rhythmic Gymnastics National Team.

METHODS
The Study Group included 60 adult females who were former rhythmic gymnasts of the Italian National Team. The Control Group included 60 adult females comparable for age, who were never involved in high level sport competitions. A standardized questionnaire was used to evaluate low back-pain symptoms.

RESULTS
Low back pain complaints were reported by 22 former rhythmic gymnasts and by 28 controls (36.6% vs. 46.6%, p: n.s.); in the ex-gymnasts the age of onset of pain was earlier than in controls. The former rhythmic gymnasts complaining low back pain reported a higher prevalence of symptoms also during the time of competitions, and retired earlier than those without pain.

CONCLUSIONS
Former elite rhythmic gymnasts reported a prevalence of low back-pain similar to sex and age matched general population. However, the rhythmic gymnasts who complained back pain during the sport activity are at risk of an early onset of symptoms after the retire from competitions. This study suggests that rhythmic gymnastics is not associated with increased risk of low back pain in the adult age.


This report provides new evidence on Rhode Island's Temporary Caregiver Insurance (TCI) law, which took effect in January 2014, based on a survey of small and medium-sized businesses in the food services and manufacturing sectors in Rhode Island, Connecticut, and Massachusetts that we carried out in December 2013 (just before the law came into effect) and in January/February 2015 (one year after the law came into effect). We collected information about firm characteristics and productivity, employee life events and work flow, and employer-provided benefits. Comparing Rhode Island employers pre-and post-law to Massachusetts and Connecticut employers over the same time period, we found little evidence of significant impacts of the law on employers (although we note that the sample size for these estimates was small; 104 employers in Rhode Island, and 133 in the other two states combined). We also asked Rhode Island employers directly about their views towards TCI one year after it came into effect and found that a majority of the 213 Rhode Island employers interviewed in 2015 support the new law. Thus, our results suggest that laws like Rhode Island's TCI may not have significant impacts on small and medium-sized employers and could garner support by such employers once they have experienced them.


Since faculty can strongly influence the overall ethical climate of the University environment (Schulte et.al 1991), the professional and ethical conducts of faculty are of special concern to the public. In general, the aim of this study is to investigate the perceptions of students and lecturers on ethics in academia and lecturer-student interaction. Lecturers of Fakulti Pengurusan dan Pembangunan Sumber Manusia, Universiti Teknologi Malaysia and final year students of the faculty and three other engineering faculties were randomly selected to answer the questionnaire on the subject. Results of the study reveal that lecturers perceive more actions as unethical than the students. Gender and academic program are found to be factors influencing students' perceptions, but only in several situations. No demographic factors influence lecturers' ethical perceptions. Results of this study disclose that students' expectations on lecturers' actions are higher regarding ethics. Respondents agree that the collective and individual action of a member in a university will affect the overall image of the University. Findings show that unethical actions that most lecturers do are using university equipment for personal activities, teaching material that the lecturers have not really mastered and canceling office hours excessively. The study found that the likeliness of respondents committing the unethical behaviour is rather low compared to the likeliness of their colleagues doing it. Among recommendations proposed; the University should develop and communicate ethical values through ethics seminar, training, colloquium, University should focus on the quality of personnel and professional development programs for both students and faculty, setting good example or role modelling by the faculty and University members. In addition, the study suggests that the curriculum should emphasize in integrating ethics in all subjects taught and the staff code of ethics has to be made more aware to all University members.


Restricted germ cell loss through apoptosis is initiated in the fetal gonad around embryonic day 13.5 (E13.5) as part of normal germ cell development. The mechanism of this germ cell attrition is unknown. We show that Bcl-x plays a crucial role in maintaining the survival of mouse germ cells during gonadogenesis. A bcl-x hypomorphic mouse was generated through the introduction of a neomycin (neo) gene into the promoter of the bcl-x gene by homologous recombination. Mice that contained two copies of the hypomorphic allele had severe reproductive defects attributed to compromised germ cell development. Males with two mutant alleles lacked spermatogonia and were sterile; females showed a severely reduced population of primordial and primary follicles and exhibited greatly impaired fertility. Primordial germ cells (PGCs) in bcl-x hypomorph mice migrated to the genital ridge by E12.5 but were depleted by E15.5, a time when Bcl-x and Bax were present. Two additional bcl-x transcripts were identified in fetal germ cells more than 300 bp upstream of previously reported start sites. Insertion of a neo cassette led to a down-regulation of the bcl-x gene at E12.5 in the hypomorph. Bax was detected by immunohistochemistry in germ cells from bcl-x hypomorph and control testes at E12.5 and E13.5. Bcl-x function was restored, and animals of both genders were fertile after removal of the neo selection cassette using Cre-mediated recombination. Alternatively, the loss of Bcl-x function in the hypomorph was corrected by the deletion of both copies of the bax gene, resulting in a restoration of germ cell survival. These findings demonstrate that the balance of Bcl-x and Bax control PGC survival and apoptosis.


Language anxiety is independent of other general types of anxiety manifestations. This paper examines the possible causes of language anxiety in that a wider range of insights can be gained for effective foreign language teaching. A close review of the literature enables us to categorize language anxiety as learner-induced, classroom-related, skill-specific, and some culture-imposed, depending on different contexts. The potential sources provide us with an insightful view in the understanding of the difficulties students may have encountered in their process of language learning.


Reactive oxygen species (ROS) play a role in the degeneration of auditory hair cells because of aging, noise trauma, or ototoxic drugs. Hydrogenation is a fundamental reduction/deoxidation reaction in living organisms. This study thus examined the potential of hydrogen to protect auditory hair cells from ROS-induced damage. To generate ROS, we applied antimycin A to explant cultures of auditory epithelia, and examined the effect of hydrogen on the protection of hair cells against ROS. Incubation with a hydrogen-saturated medium significantly reduced ROS generation and subsequent lipid peroxidation in the auditory epithelia, leading to increased survival of the hair cells. These findings show the potential of hydrogen to protect auditory hair cells from ROS-induced damage.


The evaluation of malignancy-related features often helps to determine the prognoses for patients with carcinomas. One technique, which is becoming increasingly important for assessing such prognostic features is that of Fluorescence in situ Hybridization (FISH). By counting the number of FISH signals in a stack of 2- D images of a tumor (which together constitute the 3-D image volume), it is possible to determine whether there has been any loss or gain of the target DNA sequences and thereby evaluate the stage of the disease. However, visual counting of the FISH signals in this way is a tedious, fatiguing and time-consuming task. Therefore, we have developed an automated system for the quantitative evaluation of FISH signals. We present and discuss the implementation of an image processing module that segments, characterizes and counts the FISH signals in 3-D images of thick prostate tumor tissue specimens. Possible errors in the automatic counting of signals are listed and ways to circumvent these errors are described. We define a feature vector for a FISH signal and describe how we have used the weighted feature vector to segment specific signals from noise artifacts. In addition, we present a method, which allows overlapping FISH signals to be distinguished by fitting a local Gaussian model around the intensity profile and studying the feature vector of each model. Our complete image processing module overcomes the problems of manual counting of FISH signals in 3-D images of tumor specimens, thereby providing improved diagnostic and prognostic capability in qualitative diagnostic pathology.