The bias in reversing the Box-Cox transformation in time series forecasting: An empirical study based on neural networks

The Box-Cox transformation is a technique mostly utilized to turn the probabilistic distribution of a time series data into approximately normal. And this helps statistical and neural models to perform more accurate forecastings. However, it introduces a bias when the reversion of the transformation is conducted with the predicted data. The statistical methods to perform a bias-free reversion require, necessarily, the assumption of Gaussianity of the transformed data distribution, which is a rare event in real-world time series. So, the aim of this study was to provide an effective method of removing the bias when the reversion of the Box-Cox transformation is executed. Thus, the developed method is based on a focused time lagged feedforward neural network, which does not require any assumption about the transformed data distribution. Therefore, to evaluate the performance of the proposed method, numerical simulations were conducted and the Mean Absolute Percentage Error, the Theil Inequality Index and the Signal-to-Noise ratio of 20-step-ahead forecasts of 40 time series were compared, and the results obtained indicate that the proposed reversion method is valid and justifies new studies. (C) 2014 Elsevier B.V. All rights reserved.

Expression of the classical and nonclassical HLA molecules in breast cancer

Considering that downregulation of HLA expression could represent a potential mechanism for breast carcinogenesis and metastasis, the aim of the present study was to use immunohistochemical methods to analyze the expression of HLA-Ia, HLA-DR, HLA-DQ, HLA-E, and HLA-G in invasive ductal carcinoma (IDC) of the breast and to relate this HLA profile to anatomopathological parameters. Fifty-two IDC from breast biopsies were stratified according to histological differentiation (well, moderately, and poorly differentiated) and to the presence of metastases in axillary lymph nodes. The expression of HLA molecules was assessed by immunohistochemistry, using a computer-assisted system. Overall, 31 (59.6%) out of the 52 IDC breast biopsies exhibited high expression of HLA-G, but only 14 (26.9%) showed high expression of HLA-E. A large number (41, 78.8%) of the biopsies showed low expression of HLA-Ia, while 45 (86.5%) showed high expression of HLA-DQ and 36 (69.2%) underexpressed HLA-DR. Moreover, 24 (41.2%) of 52 biopsies had both low HLA-Ia expression and high HLA-G expression, while 11 (21.2%) had low HLA-Ia expression and high HLA-E expression. These results suggest that, by different mechanisms, the downregulation of HLA-Ia, HLA-E, and HLA-DR and the upregulation of HLA-G and HLA-DQ are associated with immune response evasion and breast cancer aggressiveness.

Food of the Red Drum, Sciaenops ocellata, from Mississippi Sound

Examined digestive tracts of the red drum in Mississippi Sound contained mostly decapod crustaceans. Crustaceans accounted for 34 of 59 encountered taxa, more than reported from any other region. Nevertheless, the general diet for 104 fish with food contents out of the 107 examined is similar to that reported for red drum in several other studies from other areas. In addition to crustaceans, fishes followed by polychaetes occurred as the most important items (in 99, 43, and 15% of the drum with food, respectively). Blue crabs occurred in even more drum than the frequently encountered penaeid shrimps. Other commercial species were negligible in the diet. Sixteen large drum from Georgia beaches were also examined; unlike those from Mississippi, many of these contained echinoderms, but not polychaetes or penaeids. We suggest that the red drum’s migrations may be regulated by optimal abundance of specific types of dietary organisms.

Frequent downregulation of the transcription factor Foxa2 in lung cancer through epigenetic silencing

Purpose: We sought to determine the mechanisms of downregulation of the airway transcription factor Foxa2 in lung cancer and the expression status of Foxa2 in non-small-cell lung cancer (NSCLC). Methods: A series of 25 lung cancer cell lines were evaluated for Foxa2 protein expression, FOXA2 mRNA levels, FOXA2 mutations, FOXA2 copy number changes and for evidence of FOXA2 promoter hypermethylation. In addition, 32 NSCLCs were sequenced for FOXA2 mutations and 173 primary NSCLC tumors evaluated for Foxa2 expression using an immunohistochemical assay. Results: Out of the 25 cell lines, 13 (52%) had undetectable FOXA2 mRNA. The expression of FOXA2 mRNA and Foxa2 protein were congruent in 19/22 cells (p = 0.001). FOXA2 mutations were not identified in primary NSCLCs and were infrequent in cell lines. Focal or broad chromosomal deletions involving FOXA2 were not present. The promoter region of FOXA2 had evidence of hypermethylation, with an inverse correlation between FOXA2 mRNA expression and presence of CpG dinucleotide methylation (p < 0.0001). In primary NSCLC tumor specimens, there was a high frequency of either absence (42/173, 24.2%) or no/low expression (96/173,55.4%) of Foxa2. In 130 patients with stage I NSCLC there was a trend towards decreased survival in tumors with no/low expression of Foxa2 (HR of 1.6, 95%CI 0.9-3.1; p = 0.122). Conclusions: Loss of expression of Foxa2 is frequent in lung cancer cell lines and NSCLCs. The main mechanism of downregulation of Foxa2 is epigenetic silencing through promoter hypermethylation. Further elucidation of the involvement of Foxa2 and other airway transcription factors in the pathogenesis of lung cancer may identify novel therapeutic targets. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

A high energy perspective of the co-evolution of black holes and their host galaxies

Thanks to the Chandra and XMM–Newton surveys, the hard X-ray sky is now probed down to a flux limit where the bulk of the X-ray background is almost completely resolved into discrete sources, at least in the 2–8 keV band. Extensive programs of multiwavelength follow-up observations showed that the large majority of hard X–ray selected sources are identified with Active Galactic Nuclei (AGN) spanning a broad range of redshifts, luminosities and optical properties. A sizable fraction of relatively luminous X-ray sources hosting an active, presumably obscured, nucleus would not have been easily recognized as such on the basis of optical observations because characterized by “peculiar” optical properties. In my PhD thesis, I will focus the attention on the nature of two classes of hard X-ray selected “elusive” sources: those characterized by high X-ray-to-optical flux ratios and red optical-to-near-infrared colors, a fraction of which associated with Type 2 quasars, and the X-ray bright optically normal galaxies, also known as XBONGs. In order to characterize the properties of these classes of elusive AGN, the datasets of several deep and large-area surveys have been fully exploited. The first class of “elusive” sources is characterized by X-ray-to-optical flux ratios (X/O) significantly higher than what is generally observed from unobscured quasars and Seyfert galaxies. The properties of well defined samples of high X/O sources detected at bright X–ray fluxes suggest that X/O selection is highly efficient in sampling high–redshift obscured quasars. At the limits of deep Chandra surveys (∼10−16 erg cm−2 s−1), high X/O sources are generally characterized by extremely faint optical magnitudes, hence their spectroscopic identification is hardly feasible even with the largest telescopes. In this framework, a detailed investigation of their X-ray properties may provide useful information on the nature of this important component of the X-ray source population. The X-ray data of the deepest X-ray observations ever performed, the Chandra deep fields, allows us to characterize the average X-ray properties of the high X/O population. The results of spectral analysis clearly indicate that the high X/O sources represent the most obscured component of the X–ray background. Their spectra are harder (G ∼ 1) than any other class of sources in the deep fields and also of the XRB spectrum (G ≈ 1.4). In order to better understand the AGN physics and evolution, a much better knowledge of the redshift, luminosity and spectral energy distributions (SEDs) of elusive AGN is of paramount importance. The recent COSMOS survey provides the necessary multiwavelength database to characterize the SEDs of a statistically robust sample of obscured sources. The combination of high X/O and red-colors offers a powerful tool to select obscured luminous objects at high redshift. A large sample of X-ray emitting extremely red objects (R−K >5) has been collected and their optical-infrared properties have been studied. In particular, using an appropriate SED fitting procedure, the nuclear and the host galaxy components have been deconvolved over a large range of wavelengths and ptical nuclear extinctions, black hole masses and Eddington ratios have been estimated. It is important to remark that the combination of hard X-ray selection and extreme red colors is highly efficient in picking up highly obscured, luminous sources at high redshift. Although the XBONGs do not present a new source population, the interest on the nature of these sources has gained a renewed attention after the discovery of several examples from recent Chandra and XMM–Newton surveys. Even though several possibilities were proposed in recent literature to explain why a relatively luminous (LX = 1042 − 1043erg s−1) hard X-ray source does not leave any significant signature of its presence in terms of optical emission lines, the very nature of XBONGs is still subject of debate. Good-quality photometric near-infrared data (ISAAC/VLT) of 4 low-redshift XBONGs from the HELLAS2XMMsurvey have been used to search for the presence of the putative nucleus, applying the surface-brightness decomposition technique. In two out of the four sources, the presence of a nuclear weak component hosted by a bright galaxy has been revealed. The results indicate that moderate amounts of gas and dust, covering a large solid angle (possibly 4p) at the nuclear source, may explain the lack of optical emission lines. A weak nucleus not able to produce suffcient UV photons may provide an alternative or additional explanation. On the basis of an admittedly small sample, we conclude that XBONGs constitute a mixed bag rather than a new source population. When the presence of a nucleus is revealed, it turns out to be mildly absorbed and hosted by a bright galaxy.

The Integrated European Project "GEHA - GEnetics of Healthy Aging": recruitment, health status assessment and survival of the Italian 90+ sibpairs

The present study is part of the EU Integrated Project “GEHA – Genetics of Healthy Aging” (Franceschi C et al., Ann N Y Acad Sci. 1100: 21-45, 2007), whose aim is to identify genes involved in healthy aging and longevity, which allow individuals to survive to advanced age in good cognitive and physical function and in the absence of major age-related diseases. Aims The major aims of this thesis were the following: 1. to outline the recruitment procedure of 90+ Italian siblings performed by the recruiting units of the University of Bologna (UNIBO) and Rome (ISS). The procedures related to the following items necessary to perform the study were described and commented: identification of the eligible area for recruitment, demographic aspects related to the need of getting census lists of 90+siblings, mail and phone contact with 90+ subjects and their families, bioethics aspects of the whole procedure, standardization of the recruitment methodology and set-up of a detailed flow chart to be followed by the European recruitment centres (obtainment of the informed consent form, anonimization of data by using a special code, how to perform the interview, how to collect the blood, how to enter data in the GEHA Phenotypic Data Base hosted at Odense). 2. to provide an overview of the phenotypic characteristics of 90+ Italian siblings recruited by the recruiting units of the University of Bologna (UNIBO) and Rome (ISS). The following items were addressed: socio-demographic characteristics, health status, cognitive assessment, physical conditions (handgrip strength test, chair-stand test, physical ability including ADL, vision and hearing ability, movement ability and doing light housework), life-style information (smoking and drinking habits) and subjective well-being (attitude towards life). Moreover, haematological parameters collected in the 90+ sibpairs as optional parameters by the Bologna and Rome recruiting units were used for a more comprehensive evaluation of the results obtained using the above mentioned phenotypic characteristics reported in the GEHA questionnaire. 3. to assess 90+ Italian siblings as far as their health/functional status is concerned on the basis of three classification methods proposed in previous studies on centenarians, which are based on: • actual functional capabilities (ADL, SMMSE, visual and hearing abilities) (Gondo et al., J Gerontol. 61A (3): 305-310, 2006); • actual functional capabilities and morbidity (ADL, ability to walk, SMMSE, presence of cancer, ictus, renal failure, anaemia, and liver diseases) (Franceschi et al., Aging Clin Exp Res, 12:77-84, 2000); • retrospectively collected data about past history of morbidity and age of disease onset (hypertension, heart disease, diabetes, stroke, cancer, osteopororis, neurological diseases, chronic obstructive pulmonary disease and ocular diseases) (Evert et al., J Gerontol A Biol Sci Med Sci. 58A (3): 232-237, 2003). Firstly these available models to define the health status of long-living subjects were applied to the sample and, since the classifications by Gondo and Franceschi are both based on the present functional status, they were compared in order to better recognize the healthy aging phenotype and to identify the best group of 90+ subjects out of the entire studied population. 4. to investigate the concordance of health and functional status among 90+ siblings in order to divide sibpairs in three categories: the best (both sibs are in good shape), the worst (both sibs are in bad shape) and an intermediate group (one sib is in good shape and the other is in bad shape). Moreover, the evaluation wanted to discover which variables are concordant among siblings; thus, concordant variables could be considered as familiar variables (determined by the environment or by genetics). 5. to perform a survival analysis by using mortality data at 1st January 2009 from the follow-up as the main outcome and selected functional and clinical parameters as explanatory variables. Methods A total of 765 90+ Italian subjects recruited by UNIBO (549 90+ siblings, belonging to 258 families) and ISS (216 90+ siblings, belonging to 106 families) recruiting units are included in the analysis. Each subject was interviewed according to a standardized questionnaire, comprising extensively utilized questions that have been validated in previous European studies on elderly subjects and covering demographic information, life style, living conditions, cognitive status (SMMSE), mood, health status and anthropometric measurements. Moreover, subjects were asked to perform some physical tests (Hand Grip Strength test and Chair Standing test) and a sample of about 24 mL of blood was collected and then processed according to a common protocol for the preparation and storage of DNA aliquots. Results From the analysis the main findings are the following: - a standardized protocol to assess cognitive status, physical performances and health status of European nonagenarian subjects was set up, in respect to ethical requirements, and it is available as a reference for other studies in this field; - GEHA families are enriched in long-living members and extreme survival, and represent an appropriate model for the identification of genes involved in healthy aging and longevity; - two simplified sets of criteria to classify 90+ sibling according to their health status were proposed, as operational tools for distinguishing healthy from non healthy subjects; - cognitive and functional parameters have a major role in categorizing 90+ siblings for the health status; - parameters such as education and good physical abilities (500 metres walking ability, going up and down the stairs ability, high scores at hand grip and chair stand tests) are associated with a good health status (defined as “cognitive unimpairment and absence of disability”); - male nonagenarians show a more homogeneous phenotype than females, and, though far fewer in number, tend to be healthier than females; - in males the good health status is not protective for survival, confirming the male-female health survival paradox; - survival after age 90 was dependent mainly on intact cognitive status and absence of functional disabilities; - haemoglobin and creatinine levels are both associated with longevity; - the most concordant items among 90+ siblings are related to the functional status, indicating that they contain a familiar component. It is still to be investigated at what level this familiar component is determined by genetics or by environment or by the interaction between genetics, environment and chance (and at what level). Conclusions In conclusion, we could state that this study, in accordance with the main objectives of the whole GEHA project, represents one of the first attempt to identify the biological and non biological determinants of successful/unsuccessful aging and longevity. Here, the analysis was performed on 90+ siblings recruited in Northern and Central Italy and it could be used as a reference for others studies in this field on Italian population. Moreover, it contributed to the definition of “successful” and “unsuccessful” aging and categorising a very large cohort of our most elderly subjects into “successful” and “unsuccessful” groups provided an unrivalled opportunity to detect some of the basic genetic/molecular mechanisms which underpin good health as opposed to chronic disability. Discoveries in the topic of the biological determinants of healthy aging represent a real possibility to identify new markers to be utilized for the identification of subgroups of old European citizens having a higher risk to develop age-related diseases and disabilities and to direct major preventive medicine strategies for the new epidemic of chronic disease in the 21st century.

Problem-specific design of metaheuristics for constrained spanning tree problems

When designing metaheuristic optimization methods, there is a trade-off between application range and effectiveness. For large real-world instances of combinatorial optimization problems out-of-the-box metaheuristics often fail, and optimization methods need to be adapted to the problem at hand. Knowledge about the structure of high-quality solutions can be exploited by introducing a so called bias into one of the components of the metaheuristic used. These problem-specific adaptations allow to increase search performance. This thesis analyzes the characteristics of high-quality solutions for three constrained spanning tree problems: the optimal communication spanning tree problem, the quadratic minimum spanning tree problem and the bounded diameter minimum spanning tree problem. Several relevant tree properties, that should be explored when analyzing a constrained spanning tree problem, are identified. Based on the gained insights on the structure of high-quality solutions, efficient and robust solution approaches are designed for each of the three problems. Experimental studies analyze the performance of the developed approaches compared to the current state-of-the-art.

The Dynamics of the Policies of Ethnic Cleansing in Silesia in the Nineteenth and Twentieth Centuries

Through studying German, Polish and Czech publications on Silesia, Mr. Kamusella found that most of them, instead of trying to objectively analyse the past, are devoted to proving some essential "Germanness", "Polishness" or "Czechness" of this region. He believes that the terminology and thought-patterns of nationalist ideology are so deeply entrenched in the minds of researchers that they do not consider themselves nationalist. However, he notes that, due to the spread of the results of the latest studies on ethnicity/nationalism (by Gellner, Hobsbawm, Smith, Erikson Buillig, amongst others), German publications on Silesia have become quite objective since the 1980s, and the same process (impeded by under funding) has been taking place in Poland and the Czech Republic since 1989. His own research totals some 500 pages, in English, presented on disc. So what are the traps into which historians have been inclined to fall? There is a tendency for them to treat Silesia as an entity which has existed forever, though Mr. Kamusella points out that it emerged as a region only at the beginning of the 11th century. These same historians speak of Poles, Czechs and Germans in Silesia, though Mr. Kamusella found that before the mid-19th century, identification was with an inhabitant's local area, religion or dynasty. In fact, a German national identity started to be forged in Prussian Silesia only during the Liberation War against Napoleon (1813-1815). It was concretised in 1861 in the form of the first Prussian census, when the language a citizen spoke was equated with his/her nationality. A similar census was carried out in Austrian Silesia only in 1881. The censuses forced the Silesians to choose their nationality despite their multiethnic multicultural identities. It was the active promotion of a German identity in Prussian Silesia, and Vienna's uneasy acceptance of the national identities in Austrian Silesia which stimulated the development of Polish national, Moravian ethnic and Upper Silesian ethnic regional identities in Upper Silesia, and Polish national, Czech national, Moravian ethnic and Silesian ethnic identities in Austrian Silesia. While traditional historians speak of the "nationalist struggle" as though it were a permanent characteristic of Silesia, Mr. Kamusella points out that such a struggle only developed in earnest after 1918. What is more, he shows how it has been conveniently forgotten that, besides the national players, there were also significant ethnic movements of Moravians, Upper Silesians, Silesians and the tutejsi (i.e. those who still chose to identify with their locality). At this point Mr. Kamusella moves into the area of linguistics. While traditionally historians have spoken of the conflicts between the three national languages (German, Polish and Czech), Mr Kamusella reminds us that the standardised forms of these languages, which we choose to dub "national", were developed only in the mid-18th century, after 1869 (when Polish became the official language in Galicia), and after the 1870s (when Czech became the official language in Bohemia). As for standard German, it was only widely promoted in Silesia from the mid 19th century onwards. In fact, the majority of the population of Prussian Upper Silesia and Austrian Silesia were bi- or even multilingual. What is more, the "Polish" and "Czech" Silesians spoke were not the standard languages we know today, but a continuum of West-Slavic dialects in the countryside and a continuum of West-Slavic/German creoles in the urbanised areas. Such was the linguistic confusion that, from time to time, some ethnic/regional and Church activists strove to create a distinctive Upper Silesian/Silesian language on the basis of these dialects/creoles, but their efforts were thwarted by the staunch promotion of standard German, and after 1918, of standard Polish and Czech. Still on the subject of language, Mr. Kamusella draws attention to a problem around the issue of place names and personal names. Polish historians use current Polish versions of the Silesian place names, Czechs use current Polish/Czech versions of the place names, and Germans use the German versions which were in use in Silesia up to 1945. Mr. Kamusella attempted to avoid this, as he sees it, nationalist tendency, by using an appropriate version of a place name for a given period and providing its modern counterpart in parentheses. In the case of modern place names he gives the German version in parentheses. As for the name of historical figures, he strove to use the name entered on the birth certificate of the person involved, and by doing so avoid such confusion as, for instance, surrounds the Austrian Silesian pastor L.J. Sherschnik, who in German became Scherschnick, in Polish, Szersznik, and in Czech, Sersnik. Indeed, the prospective Silesian scholar should, Mr. Kamusella suggests, as well as the three languages directly involved in the area itself, know English and French, since many documents and books on the subject have been published in these languages, and even Latin, when dealing in depth with the period before the mid-19th century. Mr. Kamusella divides the policies of ethnic cleansing into two categories. The first he classifies as soft, meaning that policy is confined to the educational system, army, civil service and the church, and the aim is that everyone learn the language of the dominant group. The second is the group of hard policies, which amount to what is popularly labelled as ethnic cleansing. This category of policy aims at the total assimilation and/or physical liquidation of the non-dominant groups non-congruent with the ideal of homogeneity of a given nation-state. Mr. Kamusella found that soft policies were consciously and systematically employed by Prussia/Germany in Prussian Silesia from the 1860s to 1918, whereas in Austrian Silesia, Vienna quite inconsistently dabbled in them from the 1880s to 1917. In the inter-war period, the emergence of the nation-states of Poland and Czechoslovakia led to full employment of the soft policies and partial employment of the hard ones (curbed by the League of Nations minorities protection system) in Czechoslovakian Silesia, German Upper Silesia and the Polish parts of Upper and Austrian Silesia. In 1939-1945, Berlin started consistently using all the "hard" methods to homogenise Polish and Czechoslovakian Silesia which fell, in their entirety, within the Reich's borders. After World War II Czechoslovakia regained its prewar part of Silesia while Poland was given its prewar section plus almost the whole of the prewar German province. Subsequently, with the active involvement and support of the Soviet Union, Warsaw and Prague expelled the majority of Germans from Silesia in 1945-1948 (there were also instances of the Poles expelling Upper Silesian Czechs/Moravians, and of the Czechs expelling Czech Silesian Poles/pro-Polish Silesians). During the period of communist rule, the same two countries carried out a thorough Polonisation and Czechisation of Silesia, submerging this region into a new, non-historically based administrative division. Democratisation in the wake of the fall of communism, and a gradual retreat from the nationalist ideal of the homogeneous nation-state with a view to possible membership of the European Union, caused the abolition of the "hard" policies and phasing out of the "soft" ones. Consequently, limited revivals of various ethnic/national minorities have been observed in Czech and Polish Silesia, whereas Silesian regionalism has become popular in the westernmost part of Silesia which remained part of Germany. Mr. Kamusella believes it is possible that, with the overcoming of the nation-state discourse in European politics, when the expression of multiethnicity and multilingualism has become the cause of the day in Silesia, regionalism will hold sway in this region, uniting its ethnically/nationally variegated population in accordance with the principle of subsidiarity championed by the European Union.

Inbreeding Alters Activities of the Stress-Related Enzymes Chitinases and β-1,3-Glucanases

Pathogenesis-related proteins, chitinases (CHT) and β-1,3-glucanases (GLU), are stress proteins up-regulated as response to extrinsic environmental stress in plants. It is unknown whether these PR proteins are also influenced by inbreeding, which has been suggested to constitute intrinsic genetic stress, and which is also known to affect the ability of plants to cope with environmental stress. We investigated activities of CHT and GLU in response to inbreeding in plants from 13 Ragged Robin (Lychnis flos-cuculi) populations. We also studied whether activities of these enzymes were associated with levels of herbivore damage and pathogen infection in the populations from which the plants originated. We found an increase in pathogenesis-related protein activity in inbred plants from five out of the 13 investigated populations, which suggests that these proteins may play a role in how plants respond to intrinsic genetic stress brought about by inbreeding in some populations depending on the allele frequencies of loci affecting the expression of CHT and the past levels of inbreeding. More importantly, we found that CHT activities were higher in plants from populations with higher levels of herbivore or pathogen damage, but inbreeding reduced CHT activity in these populations disrupting the increased activities of this resistance-related enzyme in populations where high resistance is beneficial. These results provide novel information on the effects of plant inbreeding on plant–enemy interactions on a biochemical level.

Variation of the mechanical properties of PMMA to suit osteoporotic cancellous bone

Poly(methyl methacrylate) (PMMA) is by far the most frequently used bone substitute material for vertebroplasty. However, there are serious complications, such as cement leakage and an increased fracture rate of the adjacent vertebral bodies. The latter may be related to the mechanical properties of the augmented segment within the osteoporotic spine. A possible counter-measure is prophylactic augmentation at additional levels, but this aggravates the risk for the patient. Introduction of pores is a possible method to reduce the inherent high stiffness of PMMA. This study investigates the effect of porosity on the mechanical properties of PMMA bone cement. Different fractions of a highly viscous liquid were mixed into the PMMA during preparation. An open-porous material with adjustable mechanical properties resulted after removal of the aqueous phase. Different radiopacifiers were admixed to investigate their suitability for vertebroplasty. The final material was characterized mechanically by compressive testing, microscopically and radiologically. In addition, the monomer release subsequent to hardening was measured by means of gas chromatography. The Young's modulus in compression could be varied between 2800 +/- 70 MPa and 120 +/- 150 MPa, and the compression ultimate strength between 170 +/- 5 MPa and 8 +/- 9 MPa for aqueous fractions ranging between 0 and 50% of volume. Only a slight decrease of the Young's modulus and small changes of ultimate strength were found when the mixing time was increased. An organic hydrophilic and lipophilic radiopacifier led to a higher Young's modulus of the porous material; however, the ultimate strength was not significantly affected by adding different radiopacifiers to the porous cement. The radiopacity was lost after washing the aqueous phase out of the pores. No separation occurred between the aqueous and the PMMA phase during injection into an open porous ceramic material. The monomer released was found to increase for increasing aqueous fractions, but remained comparable in magnitude to standard PMMA. This study demonstrates that a conventional PMMA can be modified to obtain a range of mechanical properties, including those of osteoporotic bone.

A Study of the Physical Properties of Low Tin Solders

In 1947, out of the 100,000 long tons of tin con­sumed in the United States, 25,000 tons went into solder. Tin plate took 39,000 tons while babbit, bronze and coll­apsible tubes accounted for approximately 17,000 tons. Solder ranked second to tin plate and required more than the next three major uses combined.

The Diverse Impacts of the Neo-liberal Social Policies on Children’s Welfare and Social Work with Young People: The Finnish Perspective

This article discusses the impacts of globalization, neo-liberal social policies and the Finnish economic recession of the 1990s on children's and young people's welfare. It summarises some of the impacts of Finnish social policies on the everyday lives of families with children and highlights some of the features of the recent and current debates surrounding youth delinquency and the societal reactions to young generations. All this contributes to a contradictory and conflicting societal context which challenges experts in the field of child welfare social work experts to operate - as expected - at the right moment, legally and effectively. Instead of being overly-defensive for the ‘good old’ ways of practicing social work with children, the authors invite social work scholars and practitioners to reconceptualise both the concept of children's citizenship and its position both in child welfare theory and practice in the context of children's global rights.

Education and Ideologies of the Knowledge Economy: Europe and the Politics of Emulation

The Austrian philosopher Ludwig Wittgenstein famously proposed a style of philosophy that was directed against certain pictures [bild] that tacitly direct our language and forms of life. His aim was to show the fly the way out of the fly bottle and to fight against the bewitchment of our intelligence by means of language: “A picture held us captive. And we could not get outside it, for it lay in our language and language seemed to repeat it to us inexorably” (Wittgenstein 1953, 115). In this context Wittgenstein is talking of philosophical pictures, deep metaphors that have structured our language but he does also use the term picture in other contexts (see Owen 2003, 83). I want to appeal to Wittgenstein in my use of the term ideology to refer to the way in which powerful underlying metaphors in neoclassical economics have a strong rhetorical and constitutive force at the level of public policy. Indeed, I am specifically speaking of the notion of ‘the performative’ in Wittgenstein and Austin. The notion of the knowledge economy has a prehistory in Hayek (1937; 1945) who founded the economics of knowledge in the 1930s, in Machlup (1962; 1970), who mapped the emerging employment shift to the US service economy in the early 1960s, and to sociologists Bell (1973) and Touraine (1974) who began to tease out the consequences of these changes for social structure in the post-industrial society in the early 1970s. The term has been taken up since by economists, sociologists, futurists and policy experts recently to explain the transition to the so-called ‘new economy’. It is not just a matter of noting these discursive strands in the genealogy of the ‘knowledge economy’ and related or cognate terms. We can also make a number of observations on the basis of this brief analysis. First, there has been a succession of terms like ‘postindustrial economy’, ‘information economy’, ‘knowledge economy’, ‘learning economy’, each with a set of related concepts emphasising its social, political, management or educational aspects. Often these literatures are not cross-threading and tend to focus on only one aspect of phenomena leading to classic dichotomies such as that between economy and society, knowledge and information. Second, these terms and their family concepts are discursive, historical and ideological products in the sense that they create their own meanings and often lead to constitutive effects at the level of policy. Third, while there is some empirical evidence to support claims concerning these terms, at the level of public policy these claims are empirically underdetermined and contain an integrating, visionary or futures component, which necessarily remains untested and is, perhaps, in principle untestable.

The novel ATP-competitive inhibitor of the MET hepatocyte growth factor receptor EMD1214063 displays inhibitory activity against selected MET-mutated variants

The receptor tyrosine kinase MET is a prime target in clinical oncology due to its aberrant activation and involvement in the pathogenesis of a broad spectrum of malignancies. Similar to other targeted kinases, primary and secondary mutations seem to represent an important resistance mechanism to MET inhibitors. Here, we report the biologic activity of a novel MET inhibitor, EMD1214063, on cells that ectopically express the mutated MET variants M1268T, Y1248H, H1112Y, L1213V, H1112L, V1110I, V1206L, and V1238I. Our results demonstrate a dose-dependent decrease in MET autophosphorylation in response to EMD1214063 in five out of the eight cell lines (IC50 2-43nM). Blockade of MET by EMD1214063 was accompanied by a reduced activation of downstream effectors in cells expressing EMD1214063-sensitive mutants. In all sensitive mutant-expressing lines, EMD1214063 altered cell cycle distribution, primarily with an increase in G1 phase. EMD1214063 strongly influenced MET-driven biological functions, such as cellular morphology, MET-dependent cell motility and anchorage-independent growth. To assess the in vivo efficacy of EMD1214063, we used a xenograft tumor model in immunocompromised mice bearing NIH3T3 cells expressing sensitive and resistant MET mutated variants. Animals were randomized for the treatment with EMD1214063 (50mg/kg/day) or vehicle only. Remarkably, five days of EMD1214063 treatment resulted in a complete regression of the sensitive H1112L-derived tumors, while tumor growth remained unaffected in mice with L1213V tumors and in vehicle-treated animals. Collectively, the current data identifies EMD1214063 as a potent MET small molecule inhibitor with selective activity towards mutated MET variants.

The free escape continuum of diffuse ions upstream of the Earth's quasi-parallel bow shock

The Earth's bow shock is very efficient in accelerating ions out of the incident solar wind distribution to high energies (≈ 200 keV/e). Fluxes of energetic ions accelerated at the quasi-parallel bow shock, also known as diffuse ions, are best represented by exponential spectra in energy/charge, which require additional assumptions to be incorporated into these model spectra. One of these assumptions is a so-called "free escape boundary" along the interplanetary magnetic field into the upstream direction. Locations along the IBEX orbit are ideally suited for in situ measurements to investigate the existence of an upstream free escape boundary for bow shock accelerated ions. In this study we use 2 years of ion measurements from the background monitor on the IBEX spacecraft, supported by ACE solar wind observations. The IBEX Background Monitor is sensitive to protons > 14 keV, which includes the energy of the maximum flux for diffuse ions. With increasing distance from the bow shock along the interplanetary magnetic field, the count rates for diffuse ions stay constant for ions streaming away from the bow shock, while count rates for diffuse ions streaming toward the shock gradually decrease from a maximum value to ~1/e at distances of about 10 RE to 14 RE. These observations of a gradual decrease support the transition to a free escape continuum for ions of energy >14 keV at distances from 10 RE to 14 RE from the bow shock.