bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting neurodegenerative diseases: Drug discovery in a challenging arena
Authors: Abou-Gharbia Magid , Childers Wayne
Published: June 2012

Neurodegenerative diseases represent one of the health care community’s truly unmet medical needs. They can be loosely classified into two categories, acute and chronic. One of the best known chronic neurodegenerative diseases, Alzheimer’s disease, represents a serious health care problem that may well exceed the limits of current fiscal and care giver resources. No disease-modifying therapeutic agents have been identified, and the few available symptomatic treatments possess limitations in their duration of action and side effects. Despite decades of drug discovery research and numerous clinical trials, no truly effective treatment for stroke, the most prevalent acute neurodegenerative disease, has been identified. This article summarizes two recent drug discovery projects, one targeting Alzheimer’s disease and the other targeting ischemic stroke. Both projects involved design, synthesis, and biological evaluation of a novel series of heterocyclic derivatives.
Circulating Human Hepcidin-25 Concentrations Display a Diurnal Rhythm, Increase with Prolonged Fasting, and Are Reduced by Growth Hormone Administration
Authors: Troutt Jason S , Rudling Mats , Persson Lena , Ståhle Lars , Angelin Bo , Butterfield Anthony M , Schade Andrew E , Cao Guoqing , Konrad Robert J
Published: June 2012

BACKGROUND

Hepcidin-25 reduces iron absorption by binding to the intestinal iron transporter ferroportin and causing its degradation. Currently, little is known about the basal regulation of circulating hepcidin-25. In addition, although erythropoietin administration has been reported to decrease the circulating hepcidin concentration, information is limited regarding how other stimulators of erythropoiesis, such as growth hormone (GH), might alter hepcidin-25 concentrations.

METHODS

We used a sensitive and specific hepcidin-25 dual–monoclonal antibody sandwich immunoassay to measure hepcidin-25 in healthy human volunteers at various time points throughout the day and during 3 days of fasting and subsequent refeeding. We also measured hepcidin-25 concentrations in healthy volunteers after GH administration.

RESULTS

In healthy individuals, hepcidin-25 concentrations displayed a diurnal variation, with concentrations being lowest in the early morning and steadily increasing throughout the day before declining during the evening hours, a pattern that was not influenced by food intake. Prolonged fasting produced statistically significant increases in hepcidin-25 concentrations. Refeeding reversed this process, and GH administration markedly decreased hepcidin-25 concentrations.

CONCLUSIONS

Our results indicate that in humans, hepcidin-25 exhibits diurnal changes that can be altered by prolonged fasting, which increases hepcidin-25 concentrations approximately 3-fold after 3 days of fasting, possibly owing to a suppression of erythropoiesis that may occur during the fasting state to preserve tissue iron concentrations. In contrast, GH administration decreased hepcidin-25 concentrations by approximately 65%, presumably by stimulating erythropoiesis. These results indicate that circulating hepcidin-25 concentrations display much more dynamic and rapid variation than might have been anticipated previously.
Party Systems, Critical Junctures, and Cleavages in Southeast Asia
Authors: Ufen Andreas
Published: June 2012

This article differentiates between clientelist (Thailand and the Philippines) and cleavage-based parties and party systems (Malaysia and Indonesia) with reference to insights of historical institutionalism. Clientelist parties, in contrast to cleavage-based ones, often undermine democratization because, on average, representativeness is weak, bureaucracy is more politicized, and rent-seeking behavior is widespread.
Strong State and Strong Civil Society in Contemporary South Korea
Authors: Oh Jennifer S.
Published: June 2012

This article examines the impact of Korean civil society on politics since democratization. Weak mediating institutions prevent the systematic inclusion of societal actors in the policymaking process, pitting an increasingly strengthened civil society against the state. Consequently, Korean state-society relations continue to remain contentious, posing challenges to democratic governance.
North Korea's Hereditary Succession
Authors: Lim Jae-Cheon
Published: June 2012

Focusing on the early stage, this paper compares the Kim Il Sung-Kim Jong Il succession with the Kim Jong Il-Kim Jong Un succession. Analyzing their differences and similarities, the study attempts to provide a better understanding of the leadership formation of Kim Jong Un, who now rules North Korea.
Polymorphisms of the drug transporter gene ABCB1 predict side effects of treatment with cabergoline in patients with PRL adenomas
Authors: Athanasoulia A P , Sievers C , Ising M , Brockhaus A C , Yassouridis A , Stalla G K , Uhr M
Published: June 2012

Introduction

Treatment with dopamine agonists in patients with prolactin (PRL) adenomas and Parkinson's disease is associated with central side effects. Central side effects may depend on a substance's ability to pass the blood–brain barrier, which can be actively controlled by transporter molecules such as the P-glycoprotein (P-gp) encoded by theABCB1gene.

Materials and methods

We aimed to determine whether cabergoline is transported by the P-gp and whether polymorphisms of its encodingABCB1gene predict central side effects of cabergoline therapy in patients with PRL adenomas. i) In an experimental mouse model lacking the homologues of the humanABCB1gene (Abcb1abdouble knockout mouse model), we examined whether cabergoline is a substrate of the P-gp using eight mutant and eight wild-type mice. ii) In a human case–control study including 79 patients with PRL adenomas treated with cabergoline at the Max Planck Institute of Psychiatry in Munich, we investigated the association of four selectedABCB1gene single nucleotide polymorphisms (SNPs) (rs1045642, rs2032582, rs2032583 and rs2235015), with the occurrence of central side effects under cabergoline therapy.

Results

i) In the experimental mouse model, we observed that brain concentrations of cabergoline were tenfold higher in the mutant mice compared with their wild-type littermates, implying that cabergoline is indeed a substrate of the transporter P-gp at the blood–brain barrier level. ii) In the human study, we observed significant negative associations under cabergoline for the C-carriers and heterozygous CT individuals of SNP rs1045642 with two central side effects (frequency of fatigue and sleep disorders) and for the G-carriers of SNP rs2032582 with the enhancement of dizziness. For the SNPs rs2235015 and rs2032583, no associations with central side effects under cabergoline were found.

Discussion

This is the first study demonstrating that individualABCB1gene polymorphisms, reflecting a different expression and function of the P-gp, could predict the occurrence of central side effects under cabergoline. Our findings can be viewed as a step into personalised therapy in PRL adenoma patients.
Combination of sorafenib and everolimus impacts therapeutically on adrenocortical tumor models
Authors: Mariniello Barbara , Rosato Antonio , Zuccolotto Gaia , Rubin Beatrice , Cicala Maria Verena , Finco Isabella , Iacobone Maurizio , Frigo Anna Chiara , Fassina Ambrogio , Pezzani Raffaele , Mantero Franco
Published: June 2012

Treatment options are insufficient in patients with adrenocortical carcinoma (ACC). Based on the efficacy of sorafenib, a tyrosine kinase inhibitor, and everolimus, an inhibitor of the mammalian target of rapamycin in tumors of different histotype, we aimed at testing these drugs in adrenocortical cancer models. The expression of vascular endothelial growth factor and its receptors (VEGFR1–2) was studied in 18 ACCs, 33 aldosterone-producing adenomas, 12 cortisol-producing adenomas, and six normal adrenal cortex by real-time PCR and immunohistochemistry and by immunoblotting in SW13 and H295R cancer cell lines. The effects of sorafenib and everolimus, alone or in combination, were tested on primary adrenocortical cultures and SW13 and H295R cells by evaluating cell viability and apoptosis in vitro and tumor growth inhibition of tumor cell line xenografts in immunodeficient mice in vivo. VEGF and VEGFR1–2 were detected in all samples and appeared over-expressed in two-thirds of ACC specimens. Dose-dependent inhibition of cell viability was observed particularly in SW13 cells after 24 h treatment with either drug; drug combination produced markedly synergistic growth inhibition. Increasing apoptosis was observed in tumor cells treated with the drugs, particularly with sorafenib. Finally, a significant mass reduction and increased survival were observed in SW13 xenograft model undergoing treatment with the drugs in combination. Our data suggest that an autocrine VEGF loop may exist within ACC. Furthermore, a combination of molecularly targeted agents may have both antiangiogenic and direct antitumor effects and thus could represent a new therapeutic tool for the treatment of ACC.
Genome Rearrangements Caused by Depletion of Essential DNA Replication Proteins inSaccharomyces cerevisiae
Authors: Cheng Edith , Vaisica Jessica A , Ou Jiongwen , Baryshnikova Anastasia , Lu Yong , Roth Frederick P , Brown Grant W
Published: June 2012

Genetic screens of the collection of ∼4500 deletion mutants in Saccharomyces cerevisiae have identified the cohort of nonessential genes that promote maintenance of genome integrity. Here we probe the role of essential genes needed for genome stability. To this end, we screened 217 tetracycline-regulated promoter alleles of essential genes and identified 47 genes whose depletion results in spontaneous DNA damage. We further showed that 92 of these 217 essential genes have a role in suppressing chromosome rearrangements. We identified a core set of 15 genes involved in DNA replication that are critical in preventing both spontaneous DNA damage and genome rearrangements. Mapping, classification, and analysis of rearrangement breakpoints indicated that yeast fragile sites, Ty retrotransposons, tRNA genes, early origins of replication, and replication termination sites are common features at breakpoints when essential replication genes that suppress chromosome rearrangements are downregulated. We propose mechanisms by which depletion of essential replication proteins can lead to double-stranded DNA breaks near these features, which are subsequently repaired by homologous recombination at repeated elements.
On the Prospects of Whole-Genome Association Mapping inSaccharomyces cerevisiae
Authors: Connelly Caitlin F , Akey Joshua M
Published: June 2012

Advances in sequencing technology have enabled whole-genome sequences to be obtained from multiple individuals within species, particularly in model organisms with compact genomes. For example, 36 genome sequences of Saccharomyces cerevisiae are now publicly available, and SNP data are available for even larger collections of strains. One potential use of these resources is mapping the genetic basis of phenotypic variation through genome-wide association (GWA) studies, with the benefit that associated variants can be studied experimentally with greater ease than in outbred populations such as humans. Here, we evaluate the prospects of GWA studies in S. cerevisiae strains through extensive simulations and a GWA study of mitochondrial copy number. We demonstrate that the complex and heterogeneous patterns of population structure present in yeast populations can lead to a high type I error rate in GWA studies of quantitative traits, and that methods typically used to control for population stratification do not provide adequate control of the type I error rate. Moreover, we show that while GWA studies of quantitative traits in S. cerevisiae may be difficult depending on the particular set of strains studied, association studies to map cis-acting quantitative trait loci (QTL) and Mendelian phenotypes are more feasible. We also discuss sampling strategies that could enable GWA studies in yeast and illustrate the utility of this approach in Saccharomyces paradoxus. Thus, our results provide important practical insights into the design and interpretation of GWA studies in yeast, and other model organisms that possess complex patterns of population structure.
Angels, Ritual and Sacred Space in Islam
Authors: Burge S. R.
Published: June 2012

The idea of ‘sacred space’ has been discussed frequently in the study of religion, both the ways in which faith communities engage with sacred space, as well as how different religions define and authenticate their sacred spaces. This article will look at the ways in which Muslim sacred spaces are defined in Islam, looking particularly at the way in which angels are used to confirm the sanctity of particular locations. It will look notions of sacred space in relation to the Ka’ba and other places of prayer, comparing Muslim ideas with those of Judaism, Christianity and other religious traditions.
Sound of Sama: The Use of Poetical Imagery in South Asian Sufi Music
Authors: Ghani Kashshaf
Published: June 2012

In the cultural space of the subcontinent Sufi rituals constitute an important area of research, stirring academic and non-academic inquisitiveness. And in this regard no aspect of Sufi ritualism has been more contentious than the practice of Sama (Sufi musical assemblies). Frowned upon by orders such as the Qadiris and Naqshbandis; regulated by the State in the name of Shariah (Islamic Law), Sama assemblies have been, for centuries, the defining spiritual exercise of many a leading Sufi silsila. But what constitutes the sama? How does the content(s) of such a ritual arouse spiritual sensibilities? Is there any definite structure for conducting such assemblies? These are some of the questions this paper will try to answer. While analyzing the ritual content of Sufi music the vast range of mystical poetry of both classical and south Asian Sufism needs to be taken into consideration. Indeed the music of sama is not normally conceived as apart from Sufi poetry that constitute the text. These texts create a poetic idiom, rich in image and metaphor together with a discernable degree of symbolic interpretation. What sort of an image, and of whom, do these texts portray? Who constitutes the central focus of these poetical imageries? Is there any dominant ideology working behind these textual interpretations? Such questions tend to arise, an answer to which will be sought in the course of my discussion.
BRCAness: Finding the Achilles Heel in Ovarian Cancer
Authors: Rigakos Georgios , Razis Evangelia
Published: June 2012

Ovarian cancer is the leading cause of death among gynecological cancers. It exhibits great heterogeneity in tumor biology and treatment response. Germline mutations of DNA repair genes BRCA1/2 are the fundamental defects in hereditary ovarian cancer that expresses a distinct phenotype of high response rates to platinum agents, improved disease-free intervals and survival rates, and high-grade serous histology. The term “BRCAness” describes the phenotypic traits that some sporadic ovarian tumors share with tumors in BRCA1/2 germline mutation carriers and reflects similar causative molecular abnormalities. BRCA pathway studies and molecular profiling reveal BRCA-related defects in almost half of the cases of ovarian cancer. BRCA-like tumors are particularly sensitive to DNA-damaging agents (e.g., platinum agents) because of inadequate BRCA-mediated DNA repair mechanisms, such as nucleotide-excision repair and homologous recombination (HR). Additional inhibition of other DNA repair pathways leads to synthetic lethality in HR-deficient cells; this has been employed in the treatment of BRCA-like ovarian tumors with poly(ADP-ribose) polymerase inhibitors with promising results. This article presents a comprehensive review of the relevant literature on the role of BRCAness in ovarian cancer with respect to BRCA function, methods of BRCA epigenetic defect detection and molecular profiling, and the implications of BRCA dysfunction in the treatment of ovarian cancer.
Numerical investigation of transient hydration of unsaturated geosynthetic clay liners
Authors: Siemens G. , Take W.A. , Rowe R.K. , Brachman R.W.I.
Published: June 2012

ABSTRACT: Geosynthetic clay liners (GCLs) are commonly used as hydraulic barriers, owing to their low hydraulic conductivity and their ability to form a composite barrier system with geomembranes. The GCL is manufactured and placed at a low initial moisture content, and must hydrate in the field in order to function as an effective barrier. With the overlying geomembrane limiting infiltration from above, moisture must come from the underlying foundation soil. In this paper, numerical simulations are completed to calibrate models for GCL hydration followed by a sensitivity analysis on the underlying soil properties and moisture content. The results show that the driving factor used to predict the GCL hydration level is the suction value provided by the underlying soil. The GCL requires such a small quantity of moisture relative to the amount in the soil that the suction within the soil at the beginning and end of models is relatively constant. The time rate of GCL hydration was found to be mainly a function of the unsaturated properties of the GCL. A methodology is developed to predict the final GCL moisture content and time rate of hydration.
Mechanical characteristics of soft clay treated with fibre and cement
Authors: Fatahi B. , Khabbaz H. , Fatahi B.
Published: June 2012

ABSTRACT: In this study, the influence of three types of fibre – polypropylene, recycled carpet and steel – on the mechanical properties of cement-treated clay is investigated. Cement-treated clay specimens were prepared with cement contents of 5%, 10% and 15% by weight of dry soil, and cured for 14 days. To investigate and understand the influence of different fibre types and contents, three different percentages of fibre content were adopted. The results of unconfined compression tests on 90 cylindrical samples of cement-treated clay with varied cement and fibre contents are analysed to discern the relationships between these parameters and the key mechanical properties, including unconfined compressive strength and stiffness of treated soil. Furthermore, indirect tension test results of a further 90 treated soil samples have been used to determine the influence of fibre and cement content on the tensile strength of the treated soil. The fibre reinforcement increases the peak compressive strength. The addition of fibres increases the residual strength and changes the brittle behaviour of the cement-treated clay to that of a more ductile material. The tensile strength of the cement-treated clay is increased by adding carpet and steel fibres, but small quantities of polypropylene fibres do not influence the tensile strength.
Electrical resistivity method for the measurement of density changes near a probe
Authors: DIJKSTRA J. , BROERE W. , VAN TOL A.F.
Published: June 2012

In order to investigate changes in porosity in saturated silica sand, an electrical resistivity probe for physical model testing was developed. For non-conducting particles, electrical resistivity measurements in porous media actually measure the resistivity of the pore water, changes of which are directly related to porosity change. The sensor has been integrated in a measurement probe and a model pile to measure density changes continuously during penetration. This first implementation used in the geotechnical centrifuge shows the feasibility of the method, although the initial results also show some systematic errors resulting from the construction of the probe and the measurement method itself.
Manipulating the intrinsic parameters of propagule pressure: implications for bio‐invasion
Authors: Hedge Luke H. , O'Connor Wayne A. , Johnston Emma L.
Published: June 2012

Much effort has been devoted to understanding the factors promoting species colonisation, and processes that may cause small incipient populations to fail. Post colonisation and community level processes are proving to be less reliable predictors of initial population size and propagule pressure is now posited as a key predictor of species establishment. Yet, empirical studies manipulating the intrinsic parameters of propagule pressure, such as arrival frequency (number), and intensity (size) are lacking. Understanding colonisation and incipient population survival is particularly important in the field of bio‐invasions. Propagule pressure is now often cited as a key determinant of invasion success, yet we have few empirical tests manipulating the intrinsic parameters of propagule pressure. We conducted a series of factorial field experiments utilizing larvae of the cosmopolitan invasive oyster Crassostrea gigas. A newly developed technique was used to quantitatively alter the size of propagules and the frequency at which they arrive. When total propagule pressure was held constant, and the size and arrival frequency was altered, frequent small inoculations dramatically increased incipient population size >65% relative to infrequent large introductions. We also found that smaller, less dense inoculations resulted in >85% greater proportional settlement and colonisation of this cosmopolitan species. Predation altered the overall survival of incipient oyster populations, but did not alter this pattern.

Our findings may help explain patterns of ballast water and hull‐fouling introductions, as ports and harbours that receive frequent exposure to invasive propagules from the same source location will be at greater risk of invasion.
Specification of data schema mappings using weaving models
Authors: Anicic Nenad , Neskovic Sinisa , Vuckovic Milica , Cvetkovic Radovan
Published: June 2012

Weaving models are used in the model driven engineering (MDE) community for
various application scenarios related to model mappings. However, an analysis
of its suitability for specification of heterogeneous schema mappings reveals
that weaving models lack support for mapping rules and, therefore, cannot
prevent mapping specifications which are semantically meaningless, wrong or
disallowed. This paper proposes a solution which overcomes the identified
open issue by providing the explicit support for semantic mapping rules. It
is based on introduction of weaving metamodels augmented with constraints
written in OCL. The role of OCL constraints is to restrict mapping
specifications to only those which are semantically meaningful. Using well
known MDE technologies, such as EMF and QVT, an existing tool is used to
validate the presented solution. This solution is also successfully evaluated
in practice.
Describing papers and reviewers’ competences by taxonomy of keywords
Authors: Kalmukov Yordan
Published: June 2012

This article focuses on the importance of the precise calculation of
similarity factors between papers and reviewers for performing a fair and
accurate automatic assignment of reviewers to papers. It suggests that papers
and reviewers? competences should be described by taxonomy of keywords so
that the implied hierarchical structure allows similarity measures to take
into account not only the number of exactly matching keywords, but in case of
non-matching ones to calculate how semantically close they are. The paper
also suggests a similarity measure derived from the well-known and
widely-used Dice's coefficient, but adapted in a way it could be also applied
between sets whose elements are semantically related to each other (as
concepts in taxonomy are). It allows a non-zero similarity factor to be
accurately calculated between a paper and a reviewer even if they do not
share any keyword in common.
Nearest neighbor voting in high dimensional data: Learning from past occurrences
Authors: Tomasev Nenad , Mladenic Dunja
Published: June 2012

Hubness is a recently described aspect of the curse of dimensionality
inherent to nearest-neighbor methods. This paper describes a new approach for
exploiting the hubness phenomenon in k-nearest neighbor classification. We
argue that some of the neighbor occurrences carry more information than
others, by the virtue of being less frequent events. This observation is
related to the hubness phenomenon and we explore how it affects
high-dimensional k-nearest neighbor classification. We propose a new
algorithm, Hubness Information k-Nearest Neighbor (HIKNN), which introduces
the k-occurrence informativeness into the hubness-aware k-nearest neighbor
voting framework. The algorithm successfully overcomes some of the issues
with the previous hubness-aware approaches, which is shown by performing an
extensive evaluation on several types of high-dimensional data.
Indexing ordered trees for (nonlinear) tree pattern matching by pushdown automata
Authors: Travnícek J. , Janousek J. , Melichar B.
Published: June 2012

Trees are one of the fundamental data structures used in Computer Science. We
present a new kind of acyclic pushdown automata, the tree pattern pushdown
automaton and the nonlinear tree pattern pushdown automaton, constructed for
an ordered tree. These automata accept all tree patterns and nonlinear tree
patterns, respectively, which match the tree and represent a full index of
the tree for such patterns. Given a tree with n nodes, the numbers of these
distinct tree patterns and nonlinear tree patterns can be at most 2n?1 +n and
at most (2+v)n?1+2, respectively, where v is the maximal number of nonlinear
variables allowed in nonlinear tree patterns. The total sizes of
nondeterministic versions of the two pushdown automata are O(n) and O(n2),
respectively. We discuss the time complexities and show timings of our
implementations using the bit-parallelism technique. The timings show that
for a given tree the running time is linear to the size of the input pattern.
Environmental activism as a new form of political participation of the youth in Serbia
Authors: Vukelic Jelisaveta , Stanojevic Dragan
Published: June 2012

The aim of this paper is to explore whether the environmental activism is a
new form of political participation of the Serbian youth. One of the
characteristics of the postindustrial societies is a general citizen
withdrawal from the traditional channels of political participation.
Political disengagement is thought to characterize all citizens but most of
all the young people. However, although young people may have turned away
from mainstream politics, they are nevertheless concerned with a wide range
of issues that could be considered political in a broader sense of the term.
In the post-socialist Europe young people tend to be even less involved in
political life than the youth in the established democracies. However, they
are also likely to adopt novel forms of political expression. Whether the
Serbian youth follow the same pattern of political involvement, we intend to
explore in this article. In searching for the answer to this question, we
will focus our analysis on the environmental activism, as one of the forms of
the new political engagement widely accepted among young people.
Neuropsychological assessment and treatment possibilities of cognitive deficit in schizophrenic patients
Authors: Totic-Poznanovic Sanja , Pavlovic Dragan , Djordjevic Jelena , Pavlovic Aleksandra , Marinkovic Dragan
Published: June 2012

nema
The role of autofluorescence bronchoscopy in monitoring a tumorous lesion in the bronchial mucosa: a case report
Authors: Skrbic Dusan , Stojanovic Goran , Povazan Djordje , Djuric Mirna , Eri Zivka
Published: June 2012

Introduction. Autofluorescence bronchoscopy (AFB) is a diagnostic procedure
that is included in all diagnostic algorithms discovering precancerous
lesions in the large airways. Case report. We presented a 71-year-old patient
submitted to exploration due to prolonged cough. Both noninvasive and
invasive pulmonary diagnostic management was carried out. On bronchoscopy, an
endobronchial mass was detected in the apical bronchus. A positive endoscopy
finding indicated AFB which disclosed a fluorescence alteration of the tumor
mucosa and the former bronchoscopy site. Histopathological analysis of the
catheter biopsy obtained samples from the right upper lobe confirmed
fibrinous purulent pneumonia in organization. The applied treatment resulted
in regression of both symptoms and the lesion in the right upper lobe. Due to
a positive AFB finding, the patient was regularly observed over the following
three years, having had three control AFB to monitor the initial finding.
Conclusion. AFB may be utilized in the routine of everyday practice to assess
the spread of the disease, as well as in the postsurgical and long-term
follow-up of operated patients. The procedure may also be applied to enable
an easier and more reliable observation of patients with suspicious
endobronchial lesions, smokers with altered fluorescence of the bronchial
mucosa, and chronic patients.
Nitrofurantoin-induced immune-mediated lung and liver disease
Authors: Milic Rade , Plavec Goran , Tufegdzic Ivana , Tomic Ilija , Sarac Sanja , Loncarevic Olivera
Published: June 2012

Introduction. Nitrofurantoin, a furan derivative, introduced in the fifties
has widely been used as an effective agent for the treatment and prevention
of urinary tract infections (UTI). Spectrum of adverse reactions to
nitrofurantoin is wide, ranging from eosinophilic interstitial lung disease,
acute hepatitis and granulomatous reaction, to the chronic active hepatitis,
a very rare adverse effect, that can lead to cirrhosis and death. Case
report. We presented a 55-year-old female patient with eosinophilic
interstitial lung disease, severe chronic active hepatitis and several other
immune- mediated multisystemic manifestations of prolonged exposure to
nitrofurantoin because of the recurrent UTI caused by Escherichia coli. We
estimated typical radiographic and laboratory disturbances, also restrictive
ventilatory changes, severe reduction of carbon monoxide diffusion capacity
and abnormal liver function tests. Lymphocytic-eosinophylic alveolitis was
consistent with druginduced reaction. Hepatitis was confirmed by liver
biopsy. After withdrawal of nitrofurantoin and application of high dose of
glicocorticosteroids, prompt clinical and laboratory recovery was achieved.
Conclusion. Adverse drug reactions should be considered in patients with
concomitant lung and liver disease. The mainstay of treatment is drug
withdrawal and the use of immunosuppressive drugs in severe cases.
Consideration should be given to monitor lung and liver function tests during
long term nitrofurantoin therapy.
Public Policy and Teacher Education in Brazil after 1990
Authors: Guimarães Selva
Published: June 2012

The present research investigates public policy concerning teacher education in Brazil. It is a critical rereading of historical documents focusing on laws, legal documents, projects, institutional and public policies and teaching careers developed by the Brazilian state, as well as social and scientific organisations. Emphasis is given to current political, social and economic change and educational reform implemented since 1990 as well as to the effects of international decisions on the implementation of policies in Brazilian public education.
Transnational Higher Education and Sustainable Development: Current Initiatives and Future Prospects
Authors: Koehn Peter H.
Published: June 2012

Tertiary educational institutions increasingly are relied upon for sustainable development initiatives. This policy research note analyzes newly available data regarding seven key dimensions of 295 transnational sustainable development projects involving US universities. Comparative regional analysis of the projects profiled in the APLU/AAU database indicates that US universities engage in substantially fewer development projects in Central/Eastern Europe and the Middle East relative to other regions in the South. Further, these projects tend to be short term in duration, with a smaller proportion continuing to be active in 2011 and beyond. Donors or other external sources tend to be the principal impetus for projects in both regions, rather than campus faculty members. The findings suggest that one path to increasing higher education development initiatives in the Middle East and Central/Eastern Europe would center on providing opportunities and incentives for faculty at US and overseas partner institutions to build transnational contacts that lead to joint proposal initiation and submission. The future policy implications of these research findings highlight the importance of increased funding by government agencies, international organizations, NGOs, foundations and corporations for sustainable development projects undertaken through transcontinental higher education linkages of ten years' duration or longer. By expanding direct awards to higher education institutions for collaborative transnational initiatives, donors can further empower universities to address sustainable development challenges of the twenty-first century.
Education and the Labour Market in Brazil
Authors: De Oliveira Alberto , Filho Gilberto Abrantes
Published: June 2012

The aim of this article is to compare the schooling levels of individuals with the demands of the Brazilian labour market. The results demonstrate the high probability of compatibility between occupation and schooling levels. But high propensities for under-education were identified associated with skin colour and position in family. The results are consistent with Brazilian social inequality. In conclusion, although there is a dearth of qualified labour in specific segments, the widespread existence of compatibility between workers' occupations and their schooling levels suggests that companies have adapted themselves to the educational deficiencies of their workers.
Open Source in Higher Education: Towards an Understanding of Networked Universities
Authors: Quint-Rapoport Mia
Published: June 2012

This article addresses the question of understanding more about networked universities by looking at open source software developers working in academic contexts. It sketches their identities and work as an emerging professional community that both relies upon and develops digitally mediated networks and contributes to the progress of academic knowledge and scientific discoveries. The data for this study revolve around questionnaire responses from developers working on two open source software projects, one from the field of biology, the other from education. It provides a rare glimpse into a highly specialised social world. The study demonstrates how the commitments and ideals of open source software developers not only contribute to universities as digitally network institutions, but are foundational to their very constitution.
The Problem of the Welfare Profession: An Example — The Municipalisation of the Teaching Profession
Authors: Ringarp Johanna
Published: June 2012

As an answer to the welfare state's transformation and increased focus on goal- and result-oriented regulation, Swedish educational policy is in a state of change. The matter of the teaching profession's aspirations with regard to professionalisation has come up once again: reminders that reference the introduction of teacher certification in order to guarantee the quality of education have emerged from political quarters, while union quarters are pleading for greater status for the teaching profession. The article discusses whether the municipalisation of the teaching profession in 1989 was a break with the goal of Sweden's previous political debate on education - namely, a comprehensive school for all - and whether the increased control over the work of the teachers can be said to be a consequence of the reform.
The Deep Politics of War and the Curriculum of Disillusion
Authors: Smith David Geoffrey
Published: June 2012

This article examines the historic uses of the phenomenon recently defined as ‘Deep Politics' to shed light on the underlying realities of the contemporary War on Terror. Deep Politics describes the multiple uses of misinformation to marshal public sentiment in directions desired by dominant political and economic forces. Facing the reality of Deep Politics today can be a disillusioning experience for those wedded to the rhetorical tropes of democracy, human rights and the rule of law. However, as the article attempts to illustrate, drawing on indigenous knowledge practice, disillusionment can be the first step in a longer process of cultural healing, away from naïve realism to an appreciation of the sacredness, or wholeness, of life, and the courage to face and deal with the broader truth of things.
Clean People in a Clean World
Authors: Cottey Alan
Published: June 2012

Bathing is here treated as an exemplar of the widespread profligacy of prosperous people and of the continually expanding expectations for all on this overloaded planet. The author places cleanliness in a wider context, not merely of animals but of all living organisms. With this in mind, it is possible to consider, in a wider than usual manner, our responses as the possessive market society turns into something else.
Reliability of a Treatment-Based Classification System for Subgrouping People With Low Back Pain
Authors: Henry Sharon M. , Fritz Julie M. , Trombley Andrea R. , Bunn Janice Y.
Published: June 2012

Study Design

Observational, cross-sectional reliability study.

Objectives

To examine the interrater reliability of novice raters in their use of the treatment-based classification (TBC) system for low back pain and to explore the patterns of disagreement in classification errors.

Background

Although the interrater reliability of individual test items in the TBC system is moderate to good, some error persists in classification decision making. Understanding which classification errors are common could direct further refinement of the TBC system.

Methods

Using previously recorded patient data (n = 24), 12 novice raters classified patients according to the TBC schema. These classification results were combined with those of 7 other raters, allowing examination of the overall agreement using the kappa statistic, as well as agreement/disagreement among pairwise comparisons in classification assignments. A chi-square test examined differences in percent agreement between the novice and more experienced raters and differences in classification distributions between these 2 groups of raters.

Results

Among 12 novice raters, there was 80.9% agreement in the pairs of classification (κ = 0.62; 95% confidence interval: 0.59, 0.65) and an overall 75.5% agreement (κ = 0.57; 95% confidence interval: 0.55, 0.69) for the combined data set. Raters were least likely to agree on a classification of stabilization (77.5% agreement). The overall percentage of pairwise classification judgments that disagreed was 24.5%, with the most common disagreement being between manipulation and stabilization (11.0%), followed by a mismatch between stabilization and specific exercise (8.2%).

Conclusion

Additional refinement is needed to reduce rater disagreement that persists in the TBC decision-making algorithm, particularly in the stabilization category. J Orthop Sports Phys Ther 2012;42(9):797–805, Epub 7 June 2012. doi:10.2519/jospt.2012.4078
Fragment C of Tetanus Toxin: New Insights into Its Neuronal Signaling Pathway
Authors: Calvo Ana C. , Oliván Sara , Manzano Raquel , Zaragoza Pilar , Aguilera José , Osta Rosario
Published: June 2012

When Clostridium tetani was discovered and identified as a Gram-positive anaerobic bacterium of the genus Clostridium, the possibility of turning its toxin into a valuable biological carrier to ameliorate neurodegenerative processes was inconceivable. However, the non-toxic carboxy-terminal fragment of the tetanus toxin heavy chain (fragment C) can be retrogradely transported to the central nervous system; therefore, fragment C has been used as a valuable biological carrier of neurotrophic factors to ameliorate neurodegenerative processes. More recently, the neuroprotective properties of fragment C have also been described in vitro and in vivo, involving the activation of Akt kinase and extracellular signal-regulated kinase (ERK) signaling cascades through neurotrophin tyrosine kinase (Trk) receptors. Although the precise mechanism of the molecular internalization of fragment C in neuronal cells remains unknown, fragment C could be internalized and translocated into the neuronal cytosol through a clathrin-mediated pathway dependent on proteins, such as dynamin and AP-2. In this review, the origins, molecular properties and possible signaling pathways of fragment C are reviewed to understand the biochemical characteristics of its intracellular and synaptic transport.
Development of Classification Models for Identifying “True” P-glycoprotein (P-gp) Inhibitors Through Inhibition, ATPase Activation and Monolayer Efflux Assays
Authors: Rapposelli Simona , Coi Alessio , Imbriani Marcello , Bianucci Anna Maria
Published: June 2012

P-glycoprotein (P-gp) is an efflux pump involved in the protection of tissues of several organs by influencing xenobiotic disposition. P-gp plays a key role in multidrug resistance and in the progression of many neurodegenerative diseases. The development of new and more effective therapeutics targeting P-gp thus represents an intriguing challenge in drug discovery. P-gp inhibition may be considered as a valid approach to improve drug bioavailability as well as to overcome drug resistance to many kinds of tumours characterized by the over-expression of this protein. This study aims to develop classification models from a unique dataset of 59 compounds for which there were homogeneous experimental data on P-gp inhibition, ATPase activation and monolayer efflux. For each experiment, the dataset was split into a training and a test set comprising 39 and 20 molecules, respectively. Rational splitting was accomplished using a sphere-exclusion type algorithm. After a two-step (internal/external) validation, the best-performing classification models were used in a consensus predicting task for the identification of compounds named as “true” P-gp inhibitors, i.e., molecules able to inhibit P-gp without being effluxed by P-gp itself and simultaneously unable to activate the ATPase function.
Reference Gene Selection in the Desert Plant Eremosparton songoricum
Authors: Li Xiao-Shuang , Yang Hong-Lan , Zhang Dao-Yuan , Zhang Yuan-Ming , Wood Andrew J.
Published: June 2012

Eremosparton songoricum (Litv.) Vass. (E. songoricum) is a rare and extremely drought-tolerant desert plant that holds promise as a model organism for the identification of genes associated with water deficit stress. Here, we cloned and evaluated the expression of eight candidate reference genes using quantitative real-time reverse transcriptase polymerase chain reactions. The expression of these candidate reference genes was analyzed in a diverse set of 20 samples including various E. songoricum plant tissues exposed to multiple environmental stresses. GeNorm analysis indicated that expression stability varied between the reference genes in the different experimental conditions, but the two most stable reference genes were sufficient for normalization in most conditions. EsEF and Esα-TUB were sufficient for various stress conditions, EsEF and EsACT were suitable for samples of differing germination stages, and EsGAPDHand EsUBQ were most stable across multiple adult tissue samples. The Es18S gene was unsuitable as a reference gene in our analysis. In addition, the expression level of the drought-stress related transcription factor EsDREB2 verified the utility of E. songoricum reference genes and indicated that no single gene was adequate for normalization on its own. This is the first systematic report on the selection of reference genes in E. songoricum, and these data will facilitate future work on gene expression in this species.
O6-Methylguanine-Methyltransferase (MGMT) Promoter Methylation Status in Glioma Stem-Like Cells is Correlated to Temozolomide Sensitivity Under Differentiation-Promoting Conditions
Authors: Villalva Claire , Cortes Ulrich , Wager Michel , Tourani Jean-Marc , Rivet Pierre , Marquant Celine , Martin Sebastien , Turhan Ali G. , Karayan-Tapon Lucie
Published: June 2012

Glioblastoma (GBM) is the most malignant type of primary brain tumor with a very poor prognosis. The actual standard protocol of treatment for GBM patients consists of radiotherapy and concomitant temozolomide (TMZ). However, the therapeutic efficacy of this treatment is limited due to tumor recurrence and TMZ resistance. Recently isolated, glioma stem-like cells (GSCs) are thought to represent the population of tumorigenic cells responsible for GBM resistance and recurrence following surgery and chemotherapy. In addition, MGMT (O6-methylguanine-methyltransferase) methylation is considered as one of the principal mechanisms contributing to TMZ sensitivity of GBM. In this study we have isolated GSCs from 10 adult GBM patients and investigated the relationship between MGMT methylation status and Temozolomide (TMZ) sensitivity of these lines grown either in stem-like or differentiation promoting conditions. Sensitivity to TMZ was significantly associated with MGMT methylation status in cells committed to differentiation but not in stem-like cells. In addition, patients harboring highly methylated MGMT promoters had a longer overall survival. These results reveal the importance of the differentiation process when considering the predictive value of MGMT status in GSCs for clinical response to TMZ.
Neuroglobin, a Novel Target for Endogenous Neuroprotection against Stroke and Neurodegenerative Disorders
Authors: Yu Zhanyang , Liu Ning , Liu Jianxiang , Yang Kevin , Wang Xiaoying
Published: June 2012

Brain neurons and tissues respond to sublethal injury by activating endogenous protective pathways. Recently, following the failure of a large number of clinical trials for protective strategies against stroke that aim to inhibit a specific ischemia response pathway, endogenous neuroprotection has emerged as a more promising and hopeful strategy for development of therapeutics against stroke and neurodegenerative disorders. Neuroglobin (Ngb) is an oxygen-binding globin protein that is highly and specifically expressed in brain neurons. Accumulating evidence have clearly demonstrated that Ngb is an endogenous neuroprotective molecule against hypoxic/ischemic and oxidative stress-related insults in cultured neurons and animals, as well as neurodegenerative disorders such as Alzheimer’s disease, thus any pharmacological strategy that can up-regulate endogenous Ngb expression may lead to novel therapeutics against these brain disorders. In this review, we summarize recent studies about the biological function, regulation of gene expression, and neuroprotective mechanisms of Ngb. Furthermore, strategies for identification of chemical compounds that can up-regulate endogenous Ngb expression for neuroprotection against stroke and neurodegenerative disorders are discussed.