bluuebunny/crossref_metadata_2025 huggingface dataset:
A democracy we can eat: a livelihoods approach to TVET policy and provision
Authors: Kotze Astrid von
Published: December 2010

In Southern Africa, theories of adult education have remained modelled on imported paradigms. The urgency of particularly the first of the Millennium Development Goals, 'to eradicate extreme poverty and hunger' generally translates into policy and provision of skills training based on purely economistic considerations. In practice, lifelong education and learning occurs most commonly as part of other social practices and in the guise of community development. This article outlines the livelihood approach as a conceptual and methodological tool for a locally grounded understanding of what constitutes 'work' particularly in the context of poverty and high-risk environments. It argues that the principles of interconnectedness, relationality and agency are central to understanding livelihood practices and that participatory processes of data collection, dialogue and analysis should inform education and training policy. Programmes and curricula that fit in with the livelihood strategies of people have a greater chance of being supported and the process that leads to such understanding could provide a democratic model for adult education elsewhere.
The role of adult educators towards (potential) participants and their contribution to increasing participation in adult education - insights into existing research
Authors: Hippel Aiga von
Published: December 2010

Increasing participation in adult education and addressing certain (disadvantaged) target groups is not only a professed aim of educational politics on both the national and the international level, but also a pedagogical goal. Target group and participant orientation are fundamental concepts in this process. This article discusses results of a recent German research project which examined the perspective of adult educators. The question is raised as to how far adult educators believe that target groups and participant oriented quality and the promotion of competences among adult educators may contribute to an increase in enrolment in further education. By examining the attitudes of adult educators with regard to target groups and participant orientation possible ways of improving target group participation and participant orientation on the institutional level are suggested. Furthermore, the article touches upon research questions, asking how research on potential participants and actual participants could be linked to research on educational programmes and the profession.
Book review: The State, civil society and the citizen: Exploring relationships in the field of adult education in Europe
Authors: Nylander Erik
Published: December 2010

By Michal Bron Jr., Paula Guimarães and Rui Viera de Castro (Eds.) (Frankfurt am Main, Peter Lang, 2009) 229 pp., 42.50 €, ISBN 978-3-631-58593-1
Toxicity from Metals, Old Menaces and New Threats
Authors: Briner Wayne
Published: December 2010

Metals make up the bulk of the periodic table and range from the very light (e.g., beryllium) to the very heavy (e.g., the actinides). Metals are important constituents of life, drive economic activity and industry, but can also be a hazard to human health. The metals can be roughly divided into three groups. The first being those metals, such as iron and zinc, that are essential to human life and have a wide therapeutic dose range. The second group of metals, such as lead, mercury, and uranium, has no known biological role and are toxic even at low doses. The third group of metals, such as selenium and manganese, has a role in maintaining human health but has a very narrow dose range that, when exceeded, produces toxic effects. [...]
Insecticidal Activity of Essential Oil of Carum Carvi Fruits from China and Its Main Components against Two Grain Storage Insects
Authors: Fang Rui , Jiang Cai Hong , Wang Xiu Yi , Zhang Hai Ming , Liu Zhi Long , Zhou Ligang , Du Shu Shan , Deng Zhi Wei
Published: December 2010

During our screening program for agrochemicals from Chinese medicinal herbs and wild plants, the essential oil of Carum carvi fruits was found to possess strong contact toxicity against Sitophilus zeamais and Tribolium castaneum adults, with LD50 values of 3.07 and 3.29 mg/adult, respectively, and also showed strong fumigant toxicity against the two grain storage insects with LC50 values of 3.37 and 2.53 mg/L, respectively. The essential oil obtained by hydrodistillation was investigated by GC and GC-MS. The main components of the essential oil were identified to be (R)-carvone (37.98%) and D-limonene (26.55%) followed by α-pinene (5.21), cis-carveol (5.01%) and b-myrcene (4.67%). (R)-Carvone and D-limonene were separated and purified by silica gel column chromatography and preparative thin layer chromatography, and further identified by means of physicochemical and spectrometric analysis. (R)-Carvone and D-limonene showed strong contact toxicity against S. zeamais (LD50 = 2.79 and 29.86 mg/adult) and T. castaneum (LD50 = 2.64 and 20.14 mg/adult). (R)-Carvone and D-limonene also possessed strong fumigant toxicity against S. zeamais (LC50 = 2.76 and 48.18 mg/L) and T. castaneum adults (LC50 = 1.96 and 19.10 mg/L).
Synthesis of 2-(4,6-Dimethoxy-1,3,5-triazin-2-yloxyimino) Derivatives: Application in Solution Peptide Synthesis
Authors: Al-Warhi Tarfah I. , AL-Hazimi Hassan M.A. , El-Faham Ayman , Albericio Fernando
Published: December 2010

A new class of 1,3,5-triazinyloxyimino derivatives were prepared, characterized and tested for reactivity in solution peptide synthesis. The new triazinyloxyimino derivatives failed to activate the carboxyl group during formation of peptide bonds, but gave the corresponding N-triazinyl amino acid derivatives as a major product. The oxyma (ethyl 2-cyano-2-(hydroxyimino)acetate) uronium salt was superior to other uronium salts in terms of racemization, while 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT, 9) gave the best results.
Synthesis and Antitumor Activity of 3-Methyl-4-oxo-3,4-dihydroimidazo [5,1-d][1,2,3,5]tetrazine-8-carboxylates and -carboxamides
Authors: Liu Dan , Yang Jian-Guo , Cheng Jie , Zhao Lin-Xiang
Published: December 2010

Seventeen novel 3-methyl-4-oxo-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxylate and -carboxamide derivatives were synthesized and evaluated for their growth inhibition in seven human solid tumor and a human leukemia HL-60 cell lines. Compound IVa showed more activity than the other compounds and the positive control temozolomide. In the presence of 40 mg/mL of IVa, the survival rate of all tested tumor cells was less than 10%. Esters displayed more potent antitumour activity than amides and temozolomide against HL-60 cells. These compounds also exhibited considerably enhanced water-solubility.
Detection of Cartilage Oligomeric Matrix Protein Using a Quartz Crystal Microbalance
Authors: Wang Shih-Han , Shen Chi-Yen , Weng Ting-Chan , Lin Pin-Hsuan , Yang Jia-Jyun , Chen I-Fen , Kuo Shyh-Ming , Chang Shwu-Jen , Tu Yuan-Kun , Kao Yu-Hsien , Hung Chih-Hsin
Published: December 2010

Current methods for diagnosing early stage osteoarthritis (OA) based on the magnetic resonance imaging and enzyme-linked immunosorbent assay methods are specific, but require specialized laboratory facilities and highly trained personal to obtain a definitive result. In this work, a user friendly and non-invasive quartz crystal microbalance (QCM) immunosensor method has been developed to detect Cartilage Oligomeric Matrix Protein (COMP) for early stage OA diagnosis. This QCM immunosensor was fabricated to immobilize COMP antibodies utilizing the self-assembled monolayer technique. The surface properties of the immunosensor were characterized by its FTIR and electrochemical impedance spectra (EIS). The feasibility study was based on urine samples obtained from 41 volunteers. Experiments were carried out in a flow system and the reproducibility of the electrodes was evaluated by the impedance measured by EIS. Its potential dynamically monitored the immunoreaction processes and could increase the efficiency and sensitivity of COMP detection in laboratory-cultured preparations and clinical samples. The frequency responses of the QCM immunosensor changed from 6 kHz when testing 50 ng/mL COMP concentration. The linear regression equation of frequency shift and COMP concentration was determined as: y = 0.0872 x + 1.2138 (R2 = 0.9957). The COMP in urine was also determined by both QCM and EIS for comparison. A highly sensitive, user friendly and cost effective analytical method for the early stage OA diagnosis has thus been successfully developed.
National and International Standardization (International Organization for Standardization and European Committee for Standardization) Relevant for Sustainability in Construction
Authors: Krigsvoll Guri , Fumo Marina , Morbiducci Renata
Published: December 2010

Sustainability in construction has a short history in terms of principles, standardizations and applications. From the Brundtland Report “Our Common Future”, a new vision of the resource deficits, climate impacts and the social responsibility gave growth to the idea of sustainability also in design and construction. Consequently, in around 2000, the international and national organizations for standardization started to develop standards for the application of sustainable principles. This paper gives an overview of existing and planned standards, and examples on how to use them as a framework for the development of methods and tools for assessment.
Green Jobs in Australia: A Status Report
Authors: Thomas Ian , Sandri Orana , Hegarty Kathryn
Published: December 2010

This paper captures the breadth of complexity in the debate about ‘green jobs’ as the world seeks to transition to a ‘low carbon economy’ and to reduce greenhouse gas emissions through the reduction of reliance for energy on the burning of fossil fuels. A consideration is provided within both the Australian and international contexts of the current assertions and projections regarding green jobs, their definition and location in the economy. The substantive focus of the paper is on the development of these notions in the Australian context. We consider the understanding brought to the term and explore some of the intersections for vocational employment and training which have emerged in debate about the ways in which nations will manage the carbon pollution reduction imperative. We explore the ways forward for a coherent understanding of the need to build capacity for green jobs.
The Cyanobacteria Derived Toxin Beta-N-Methylamino-L-Alanine and Amyotrophic Lateral Sclerosis
Authors: Banack Sandra A. , Caller Tracie A. , Stommel Elijah W.
Published: December 2010

There is mounting evidence to suggest that environmental factors play a major role in the development of neurodegenerative diseases like ALS (Amyotrophic Lateral Sclerosis). The non-protein amino acid beta-N-methylamino-L-alanine (BMAA) was first associated with the high incidence of Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex (ALS/PDC) in Guam, and has been implicated as a potential environmental factor in ALS, Alzheimer’s disease, and other neurodegenerative diseases. BMAA has a number of toxic effects on motor neurons including direct agonist action on NMDA and AMPA receptors, induction of oxidative stress, and depletion of glutathione. As a non-protein amino acid, there is also the strong possibility that BMAA could cause intraneuronal protein misfolding, the hallmark of neurodegeneration. While an animal model for BMAA-induced ALS is lacking, there is substantial evidence to support a link between this toxin and ALS. The ramifications of discovering an environmental trigger for ALS are enormous. In this article, we discuss the history, ecology, pharmacology and clinical ramifications of this ubiquitous, cyanobacteria-derived toxin.
Spider-Venom Peptides as Therapeutics
Authors: Saez Natalie J. , Senff Sebastian , Jensen Jonas E. , Er Sing Yan , Herzig Volker , Rash Lachlan D. , King Glenn F.
Published: December 2010

Spiders are the most successful venomous animals and the most abundant terrestrial predators. Their remarkable success is due in large part to their ingenious exploitation of silk and the evolution of pharmacologically complex venoms that ensure rapid subjugation of prey. Most spider venoms are dominated by disulfide-rich peptides that typically have high affinity and specificity for particular subtypes of ion channels and receptors. Spider venoms are conservatively predicted to contain more than 10 million bioactive peptides, making them a valuable resource for drug discovery. Here we review the structure and pharmacology of spider-venom peptides that are being used as leads for the development of therapeutics against a wide range of pathophysiological conditions including cardiovascular disorders, chronic pain, inflammation, and erectile dysfunction.
Strategy for Treating Motor Neuron Diseases Using a Fusion Protein of Botulinum Toxin Binding Domain and Streptavidin for Viral Vector Access: Work in Progress
Authors: Drachman Daniel B. , Adams Robert N. , Balasubramanian Uma , Lu Yang
Published: December 2010

Although advances in understanding of the pathogenesis of amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) have suggested attractive treatment strategies, delivery of agents to motor neurons embedded within the spinal cord is problematic. We have designed a strategy based on the specificity of botulinum toxin, to direct entry of viral vectors carrying candidate therapeutic genes into motor neurons. We have engineered and expressed fusion proteins consisting of the binding domain of botulinum toxin type A fused to streptavidin (SAv). This fusion protein will direct biotinylated viral vectors carrying therapeutic genes into motor nerve terminals where they can enter the acidified endosomal compartments, be released and undergo retrograde transport, to deliver the genes to motor neurons. Both ends of the fusion proteins are shown to be functionally intact. The binding domain end binds to mammalian nerve terminals at neuromuscular junctions, ganglioside GT1b (a target of botulinum toxin), and a variety of neuronal cells including primary chick embryo motor neurons, N2A neuroblastoma cells, NG108-15 cells, but not to NG CR72 cells, which lack complex gangliosides. The streptavidin end binds to biotin, and to a biotinylated Alexa 488 fluorescent tag. Further studies are in progress to evaluate the delivery of genes to motor neurons in vivo, by the use of biotinylated viral vectors.
Monkeypox Virus Infections in Small Animal Models for Evaluation of Anti-Poxvirus Agents
Authors: Hutson Christina L. , Damon Inger K.
Published: December 2010

An ideal animal model for the study of a human disease is one which utilizes a route of infection that mimics the natural transmission of the pathogen; the ability to obtain disease with an infectious dose equivalent to that causing disease in humans; as well having a disease course, morbidity and mortality similar to that seen with human disease. Additionally, the animal model should have a mode(s) of transmission that mimics human cases. The development of small animal models for the study of monkeypox virus (MPXV) has been quite extensive for the relatively short period of time this pathogen has been known, although only a few of these models have been used to study anti-poxvirus agents. We will review those MPXV small animal models that have been developed thus far for the study of therapeutic agents.
Mining Health Care Administrative Data with Temporal Association Rules on Hybrid Events
Authors: Sacchi L. , Cerra C. , Fratino P. , Bellazzi R. , Concaro S.
Published: December 2010

Objective: The analysis of administrative health care data can be helpful to conveniently assess health care activities. In this context temporal data mining techniques can be suitably exploited to get a deeper insight into the processes underlying health care delivery. Inthis paperwepresent an algorithm for the extraction of temporal association rules (TARs) on sequences of hybrid events and its application on health care administrative databases.

Methods: We propose a method that extends TAR mining by managing hybrid events, namely events characterized by a heterogeneous temporal nature. Hybrid events include both point-like events (e.g. ambulatory visits) and interval-like events (e.g. drug consumption). The definition of user-defined rule templates can be optionally used to constrain the search only to the extraction of a subset of interesting rules. A TAR post-pruning strategy, based on a case-control approach, is also presented.

Results: We analyzed the administrative database of diabetic patients in charge to the regional health care agency (ASL) of Pavia. TAR mining allowed to find patterns specifically related to the diabetic population in comparison with a control group, as well as to check the compliance of the actual clinical careflow with the ASL recommendations.

Conclusion: The experimental results highlighted the main potentials of the algorithm, such as the opportunity to detect interesting temporal relationships between diagnostic or therapeutic patterns, or to check the adherence of past temporal behaviors to specific expected paths (e.g. guidelines) or to discover new knowledge that could be implicitly hidden in the data.
Rapid Assessment of Clinical Information Systems in the Healthcare Setting
Authors: Ash J. S. , Sittig D. F. , Bunce A. , Guappone K. , Dykstra R. , Carpenter J. , Richardson J. , Wright A. , McMullen C. K.
Published: December 2010

Objective: Recent legislation in the United States provides strong incentives for implementation of electronic health records (EHRs). The ensuing transformation in U. S. health care will increase demand for new methods to evaluate clinical informatics interventions. Timeline constraints and a rapidly changing environment will make traditional evaluation techniques burdensome. This paper describes an anthropological approach that provides a fast and flexible way to evaluate clinical information systems.

Methods: Adapting mixed-method evaluation approaches from anthropology, we describe a rapid assessment process (RAP) for assessing clinical informatics interventions in health care that we developed and used during seven site visits to diverse community hospitals and primary care settings in the U. S.

Setting: Our multidisciplinary team used RAP to evaluate factors that either encouraged people to use clinical decision support (CDS) systems or interfered with use of these systems in settings ranging from large urban hospitals to single-practitioner, private family practices in small towns.

Results: Critical elements of the method include: 1) developing a fieldwork guide; 2) carefully selecting observation sites and participants; 3) thoroughly preparing for site visits; 4) partnering with local collaborators; 5) collecting robust data by using multiple researchers and methods; and 6) analyzing and reporting data in a structured manner helpful to the oraganizations being evaluated.

Conclusions: RAP, iteratively developed over the course of visits to seven clinical sites across the U.S., has succeeded in allowing a multidisciplinary team of informatics researchers to plan, gather and analyze data, and report results in a maximally efficient manner.
Development of ICF Code Selection Tools for Mental Health Care
Authors: Miura Y. , Takemura T. , Ashida N. , Nakagawa R. , Mineno T. , Matsumura Y. , Manabe S.
Published: December 2010

Background: The International Classification of Functioning, Disability and Health (ICF) has been available as a means of coding life functions but the coding process is cumbersome due to the large number of ICF codes. In the current study, we developed ICF code selection tools to support the coding of activity and participation data recorded in domiciliary mental health care reports.

Methods: We first developed a search system to facilitate the selection of ICF codes by tracking back through codes’ conceptual trees using a directory tool. We performed a morphological analysis on the training data set to correlate nouns with the ICF codes and obtained an analysis corpus to which numerical scores representing the frequencies of associated ICF codes for each noun were assigned. Based on the obtained corpus we developed a full-text search tool, which could simplify ICF coding relative to that performed using the directory tool. We then evaluated the usefulness of the former tool on the test data set.

Results: Using the full-text search tool, correct ICF codes were recorded in the first candidate list for only 54.2% of sentences. However, correct ICF codes appeared on the combined candidate lists for 90.1% of sentences and on the top three candidate lists for 71.7%. In a specific case (General Tasks and Demands), 100% of the correct codes were included on the combined candidate lists.

Conclusion: We developed selection tools that effectively supported ICF coding, although it was impossible to fully automate ICF coding. This indicated that ICF codes could more effectively be applied to mental health care.
Brønsted acid-promoted azide–olefin [3 + 2] cycloadditions for the preparation of contiguous aminopolyols: The importance of disiloxane ring size to a diastereoselective, bidirectional approach to zwittermicin A
Authors: Muchalski Hubert , Hong Ki Bum , Johnston Jeffrey N
Published: December 2010

We report the first study of substrate-controlled diastereoselection in a double [3 + 2] dipolar cycloaddition of benzyl azide with α,β-unsaturated imides. Using a strong Brønsted acid (triflic acid) to activate the electron deficient imide π-bond, high diastereoselection was observed provided that a 1,1,3,3-tetraisopropoxydisiloxanylidene group (TIPDS) is used to restrict the conformation of the central 1,3-anti diol. This development provides a basis for a stereocontrolled approach to the aminopolyol core of (−)-zwittermicin A using a bidirectional synthesis strategy.
The Role of Osteoclast-Associated Receptor in Osteoimmunology
Authors: Nemeth Katharina , Schoppet Michael , Al-Fakhri Nadia , Helas Susann , Jessberger Rolf , Hofbauer Lorenz C. , Goettsch Claudia
Published: December 2010

The term osteoimmunology is coined for molecular and cellular cross talk between the skeletal and immune system. Immunomodulatory signals have long been implicated as key regulators of bone metabolism. Recently, osteoclast-associated receptor (OSCAR), an IgG-like receptor, has been identified as an important osteoimmunological mediator. OSCAR expression in bone is highly conserved across different species, and the molecule is an important costimulatory receptor for osteoclast differentiation through activation of NFATc1. In humans, OSCAR is expressed by macrophages, monocytes, and monocyte-derived dendritic cells and modulates the response of the innate and adaptive immune systems by promoting cell activation and maturation, Ag presentation, and proinflammatory circuits. Human studies indicate that OSCAR may contribute to the pathogenesis and severity of osteoporosis and rheumatoid arthritis. In this paper, we review the structure-function relationship, expression pattern, and physiological role of OSCAR in osteoimmunology and summarize its potential implications for human diseases.
Neuroinflammation Screening in Immunotherapy Trials against Alzheimer's Disease
Authors: Andreasen Niels , Blennow Kaj , Zetterberg Henrik
Published: December 2010

Due to side effects in the form of meningoencephalitis in the interrupted phase II AN1792 trial of active antiamyloidβ(Aβ) immunization against Alzheimer's disease (AD), there has been concern that anti-Aβimmunization may cause destructive neuroinflammation. Here, we report on two patients fulfilling clinical AD criteria who were diagnosed with Lyme neuroborreliosis during screening before inclusion in anti-Aβimmunotherapy trials. The two cases illustrate the necessity of careful biochemical screening for neuroinflammatory/neuroinfectious conditions before an AD diagnosis is made and before clinical AD patients are included in trials of therapy that could impact the immune system. Should the two cases have been included and deteriorated, additional investigations might have led to the erroneous conclusion that therapy-induced meningoencephalitis had occurred.
Formation and Repair of Tobacco Carcinogen‐Derived Bulky DNA Adducts
Authors: Hang Bo
Published: December 2010

DNA adducts play a central role in chemical carcinogenesis. The analysis of formation and repair of smoking‐related DNA adducts remains particularly challenging as both smokers and nonsmokers exposed to smoke are repetitively under attack from complex mixtures of carcinogens such as polycyclic aromatic hydrocarbons and N‐nitrosamines. The bulky DNA adducts, which usually have complex structure, are particularly important because of their biological relevance. Several known cellular DNA repair pathways have been known to operate in human cells on specific types of bulky DNA adducts, for example, nucleotide excision repair, base excision repair, and direct reversal involving O6‐alkylguanine DNA alkyltransferase or AlkB homologs. Understanding the mechanisms of adduct formation and repair processes is critical for the assessment of cancer risk resulting from exposure to cigarette smoke, and ultimately for developing strategies of cancer prevention. This paper highlights the recent progress made in the areas concerning formation and repair of bulky DNA adducts in the context of tobacco carcinogen‐associated genotoxic and carcinogenic effects.
Biosynthesis and Virulent Behavior of Lipids Produced byMycobacterium tuberculosis: LAM and Cord Factor: An Overview
Authors: Rajni  , Rao Nisha , Meena Laxman S.
Published: December 2010

Mycobacterium tuberculosisis the causative agent of tuberculosis disease, which has developed a myriad of exceptional features contributing to its survival within the hostile environment of host cell. Unique cell wall structure with high lipid content plays an imperative role in the pathogenicity of mycobacteria. Cell wall components of MTB such as lipoarabinomannan and Trehalose dimycolate (cord factor) are virulent in nature apart from its virulence genes. Virulent effect of these factors on host cells reduces host cell immunity. LAM has been known to inhibit phagosome maturation by inhibiting the Ca2+/calmodulin phosphatidyl inositol-3-kinase hvps34 pathways. Moreover, TDM (Trehalose dimycolate) also inhibits fusion between phospholipid vesicles and migration of polymorphonuclear neutrophils. The objective of this paper is to understand the virulence of LAM and cord factor on host cell which might be helpful to design an effective drug against tuberculosis.
Biomarkers of Alzheimer′s Disease: From Central Nervous System to Periphery?
Authors: Mossello Enrico , Ballini Elena , Mello Anna Maria , Tarantini Francesca , Simoni David , Baldasseroni Samuele , Marchionni Niccolò
Published: December 2010

Alzheimer′s Disease (AD) is the most frequent form of dementia and represents one of the main causes of disability among older subjects. Up to now, the diagnosis of AD has been made according to clinical criteria. However, the use of such criteria does not allow an early diagnosis, as pathological alterations may be apparent many years before the clear‐cut clinical picture. An early diagnosis is even more valuable to develop new treatments, potentially interfering with the pathogenetic process. During the last decade, several neuroimaging and cerebrospinal fluid (CSF) parameters have been introduced to allow an early and accurate detection of AD patients, and, recently, they have been included among research criteria for AD diagnosis. However, their use in clinical practice suffers from limitations both in accuracy and availability. The increasing amount of knowledge about peripheral biomarkers will possibly allow the future identification of reliable and easily available diagnostic tests.
Insight into Glutamate Excitotoxicity from Synaptic Zinc Homeostasis
Authors: Takeda Atsushi
Published: December 2010

Zinc is released from glutamatergic (zincergic) neuron terminals in the hippocampus, followed by the increase in Zn2+ concentration in the intracellular (cytosol) compartment, as well as that in the extracellular compartment. The increase in Zn2+ concentration in the intracellular compartment during synaptic excitation is mainly due to Zn2+ influx through calcium‐permeable channels and serves as Zn2+ signaling as well as the case in the extracellular compartment. Synaptic Zn2+ homeostasis is important for glutamate signaling and altered under numerous pathological processes such as Alzheimer′s disease. Synaptic Zn2+ homeostasis might be altered in old age, and this alteration might be involved in the pathogenesis and progression of Alzheimer′s disease; Zinc may play as a key‐mediating factor in the pathophysiology of Alzheimer′s disease. This paper summarizes the role of Zn2+ signaling in glutamate excitotoxicity, which is involved in Alzheimer′s disease, to understand the significance of synaptic Zn2+ homeostasis in the pathophysiology of Alzheimer′s disease.
Manganese Inhalation as a Parkinson Disease Model
Authors: Ordoñez-Librado José Luis , Anaya-Martínez Verónica , Gutierrez-Valdez Ana Luisa , Colín-Barenque Laura , Montiel-Flores Enrique , Avila-Costa Maria Rosa
Published: December 2010

The present study examines the effects of divalent and trivalent Manganese (Mn2+/Mn3+) mixture inhalation on mice to obtain a novel animal model of Parkinson disease (PD) inducing bilateral and progressive dopaminergic cell death, correlate those alterations with motor disturbances, and determine whetherL-DOPA treatment improves the behavior, to ensure that the alterations are of dopaminergic origin. CD-1 male mice inhaled a mixture of Manganese chloride and Manganese acetate, one hour twice a week for five months. Before Mn exposure, animals were trained to perform motor function tests and were evaluated each week after the exposure. By the end of Mn exposure, 10 mice were orally treated with 7.5 mg/kgL-DOPA. After 5 months of Mn mixture inhalation, striatal dopamine content decreased 71%, the SNc showed important reduction in the number of TH-immunopositive neurons, mice developed akinesia, postural instability, and action tremor; these motor alterations were reverted withL-DOPA treatment. Our data provide evidence that Mn2+/Mn3+mixture inhalation produces similar morphological, neurochemical, and behavioral alterations to those observed in PD providing a useful experimental model for the study of this neurodegenerative disease.
Limitations of Animal Models of Parkinson's Disease
Authors: Potashkin J. A. , Blume S. R. , Runkle N. K.
Published: December 2010

Most cases of Parkinson's disease (PD) are sporadic. When choosing an animal model for idiopathic PD, one must consider the extent of similarity or divergence between the physiology, anatomy, behavior, and regulation of gene expression between humans and the animal. Rodents and nonhuman primates are used most frequently in PD research because when a Parkinsonian state is induced, they mimic many aspects of idiopathic PD. These models have been useful in our understanding of the etiology of the disease and provide a means for testing new treatments. However, the current animal models often fall short in replicating the true pathophysiology occurring in idiopathic PD, and thus results from animal models often do not translate to the clinic. In this paper we will explain the limitations of animal models of PD and why their use is inappropriate for the study of some aspects of PD.
Multiple Sclerosis: Are Protective Immune Mechanisms Compromised by a Complex Infectious Background?
Authors: Krone Bernd , Grange John M.
Published: December 2010

The immunological background of multiple sclerosis (MS) manifests as an altered reactivity against a diverse range of infections, particularly with the Epstein-Barr virus. Although this could be only an epiphenomenon of a more generalised dysfunction of the immune system in MS, it is also possible that a complex infectious background forms the basis of a specific immune dysregulation finally causing the disease. It is thus suggested that the complex infectious background bears the key for an understanding of the immune pathogenesis of the disease. It appears probable that improved standards of hygiene cause regulatory defects in the immune system, allowing the abnormal expression of human endogenous retroviral (HERV) genes. On the basis of epidemiological observations we describe how a failure of expansion or an eclipse of a subfraction of self-antigen-specific CD8+T cells mediating immune repair, and a deleterious mode of action of HERV gene products, could underlie the pathogenesis of MS.
An Intron 7 Polymorphism in APP Affects the Age of Onset of Dementia in Down Syndrome
Authors: Jones Emma L. , Ballard Clive G. , Prasher Vee P. , Arno Matthew , Tyrer Stephen , Moore Brian , Hanney Maria Luisa
Published: December 2010

People with Down syndrome (DS) develop Alzheimer′s disease (AD) with an early age of onset. A tetranucleotide repeat, attt5−8, in intron 7 of the amyloid precursor protein has been associated with the age of onset of AD in DS in a preliminary study. The authors examine the impact of this polymorphism in a larger cohort of individuals with DS.
Adults with DS were genotyped for attt5−8 and APOE. The results were analysed with respect to the age of onset of dementia. The presence of three copies of the six‐repeat allele resulted in onset of dementia seven years earlier than in the presence of other genotypes. Further study is essential to elucidate the mechanism by which this polymorphism functions, with an exciting opportunity to identify novel treatment targets relevant for people with DS and AD.
The Role of Zinc in Alzheimer′s Disease
Authors: Watt Nicole T. , Whitehouse Isobel J. , Hooper Nigel M.
Published: December 2010

Zinc, the most abundant trace metal in the brain, has numerous functions, both in health and in disease. Zinc is released into the synaptic cleft of glutamatergic neurons alongside glutamate from where it interacts and modulates NMDA and AMPA receptors. In addition, zinc has multifactorial functions in Alzheimer′s disease (AD). Zinc is critical in the enzymatic nonamyloidogenic processing of the amyloid precursor protein (APP) and in the enzymatic degradation of the amyloid‐β (Aβ) peptide. Zinc binds to Aβ promoting its aggregation into neurotoxic species, and disruption of zinc homeostasis in the brain results in synaptic and memory deficits. Thus, zinc dyshomeostasis may have a critical role to play in the pathogenesis of AD, and the chelation of zinc is a potential therapeutic approach.
Tocilizumab: A Review of Its Safety and Efficacy in Rheumatoid Arthritis
Authors: Jones Graeme , Ding Changhai
Published: December 2010

Recent years have seen many exciting developments in the treatment of rheumatoid arthritis. Tocilizumab (TCZ) is a monoclonal antibody which inhibits the interleukin-6 receptor. After initial studies in Japan, it has been extensively studied in five multicentre clinical trials. This report summarises the key efficacy and toxicity findings from the major clinical trials. TCZ works quickly and effectively in rheumatoid arthritis either as monotherapy or in combination with other agents in early disease, DMARD inadequate responders, seronegative disease and after anti-TNF failure. The toxicity profile is manageable but includes infections (most notably skin and soft tissue), increases in serum cholesterol, transient decreases in neutrophil count and abnormal liver function tests (especially in combination with methotrexate). In summary, there is sufficient evidence to make TCZ a first line biologic therapy for rheumatoid arthritis especially for those who are unable to take methotrexate or who fail anti-TNF therapy.
Pseudodifferential calculus on a singular foliation
Authors: Androulidakis Iakovos , Skandalis Georges
Published: December 2010

In a previous paper ([1]), we associated a holonomy groupoid and a C*-algebra to any singular foliation

(M,\mathcal F)

. Using these, we construct the associated pseudodifferential calculus. This calculus gives meaning to a Laplace operator of any singular foliation

\mathcal F

on a compact manifold

M

, and we show that it can be naturally understood as a positive, unbounded, self-adjoint operator on

L^2(M)

.
Effects of experimental warming and increased ultraviolet B radiation on the Mediterranean plankton food web
Authors: Vidussi Francesca , Mostajir Behzad , Fouilland Eric , Le Floc'h Emilie , Nouguier Jean , Roques Cècile , Got Patrice , Thibault-Botha Delphine , Bouvier Thierry , Troussellier Marc
Published: December 2010

The responses of the plankton food web to increases in temperature and ultraviolet B radiation (UVBR, 280–320 nm) were experimentally investigated at a coastal Mediterranean site during spring. Eight moored mesocosms were used to compare natural plankton food web responses (control mesocosms) with three treatments simulating expected future local temperature and UVBR increases, as follows: (1) 3°C increase in water temperature, (2) 20% increase in incident UVBR, and (3) simultaneous 3°C increase in water temperature and 20% increase in incident UVBR. The plankton food web was resistant to elevated UVBR, having only moderate effects on plankton abundances and structure. In contrast, warming induced significant shifts in the plankton food web structure and function. Specifically, the abundance of protozooplankton (ciliates and flagellates) increased and the development time of copepods from nauplii to adults decreased. In the warm mesocosms, the emergence of copepod adult stages midway through the experiment resulted in a decrease in ciliates and consequently in an increase in heterotrophic flagellates. One unexpected result was that warming reduced the abundance of heterotrophic bacteria midway through the experiment. These results indicate a trophic‐cascade effect under warming. The increase in adult copepods diminishes ciliates and in turn favors heterotrophic flagellates that consume bacteria. Warming also induced an increase in net oxygen production, indicating an increase in net primary production.
The two faces of cirrus clouds
Authors: Barahona D. , Nenes A.
Published: December 2010

Abstract. Low ice crystal concentration and sustained in-cloud supersaturation, commonly found in cloud observations at low temperature, challenge our understanding of cirrus formation. Heterogeneous freezing from effloresced ammonium sulfate, glassy aerosol, dust and black carbon are proposed to cause these phenomena; low updrafts however is required for cirrus characteristics to agree with observations and is at odds with the gravity wave spectrum in the upper troposphere. Instead, background temperature fluctuations can establish a "dynamical equilibrium" between ice production and sedimentation loss that explains low temperature cirrus properties. This newly-discovered state is favored at low temperatures, does not require heterogeneous nuclei to occur, and is insensitive to their presence. Our understanding of cirrus clouds and their role in anthropogenic climate change is reshaped, as the type of dynamical forcing will set these clouds in one of two "preferred" microphysical regimes with very different susceptibility to aerosol.
Ceilometer lidar comparison: backscatter coefficient retrieval and signal-to-noise ratio determination
Authors: Heese B. , Flentje H. , Althausen D. , Ansmann A. , Frey S.
Published: December 2010

Abstract. The potential of a new generation of ceilometer instruments for aerosol monitoring has been studied in the Ceilometer Lidar Comparison (CLIC) study. The used ceilometer was developed by Jenoptik, Germany, and is designed to find both thin cirrus clouds at tropopause level and aerosol layers at close ranges during day and night-time. The comparison study was performed to determine up to which altitude the ceilometers are capable to deliver particle backscatter coefficient profiles. For this, the derived ceilometer profiles are compared to simultaneously measured lidar profiles at the same wavelength. The lidar used for the comparison was the multi-wavelengths Raman lidar PollyXT. To demonstrate the capabilities and limits of ceilometers for the derivation of particle backscatter coefficient profiles from their measurements two examples of the comparison results are shown. Two cases, a daytime case with high background noise and a less noisy night-time case, are chosen. In both cases the ceilometer profiles compare well with the lidar profiles in atmospheric structures like aerosol layers or the boundary layer top height. However, the determination of the correct magnitude of the particle backscatter coefficient needs a calibration of the ceilometer data with an independent measurement of the aerosol optical depth by a sun photometer. To characterizes the ceilometers signal performance with increasing altitude a comprehensive signal-to-noise ratio study was performed. During daytime the signal-to-noise ratio is higher than 1 up to 4–5 km depending on the aerosol content. In our night-time case the SNR is higher than 1 even up to 8.5 km, so that also aerosol layers in the upper troposphere had been detected by the ceilometer.
Satellite remote sensing of Asian aerosols: a case study of clean, polluted, and Asian dust storm days
Authors: Lee K. H. , Kim Y. J.
Published: December 2010

Abstract. In East Asia, satellite observation is important because aerosols from natural and anthropogenic sources have been recognized as a major source of regional and global air pollution. However, retrieving aerosols properties from satellite observations over land can be difficult because of the surface reflection, complex aerosol composition, and aerosol absorption. In this study, a new aerosol retrieval method called as the Moderate Resolution Imaging Spectroradiometer (MODIS) satellite aerosol retrieval (MSTAR) was developed and applied to three different aerosol event cases over East Asia. MSTAR uses a separation technique that can distinguish aerosol reflectance from top-of-atmosphere (TOA) reflectance. The aerosol optical thickness (AOT) was determined by comparing this aerosol reflectance with pre-calculated values. Three case studies show how the methodology identifies discrepancies between measured and calculated values to retrieve more accurate AOT. The comparison between MODIS and the Aerosol Robotic Network (AERONET) showed improvement using the suggested methodology with the cluster-based look-up-tables (LUTs) (linear slope = 0.94, R = 0.92) than using operational MODIS collection 5 aerosol products (linear slope = 0.78, R = 0.87). In conclusion, the suggested methodology is shown to work well with aerosol models acquired by statistical clustering of the observation data in East Asia.
A network of autonomous surface ozone monitors in Antarctica: technical description and first results
Authors: Bauguitte S. J.-B. , Brough N. , Frey M. M. , Jones A. E. , Maxfield D. J. , Roscoe H. K. , Rose M. C. , Wolff E. W.
Published: December 2010

Abstract. A suite of 10 autonomous ozone monitors, each powered using renewable energy, was developed and built to study surface ozone in Antarctica during the International Polar Year (2007–2009). The monitoring systems were deployed in a network around the Weddell Sea sector of coastal Antarctica with a transect up onto the Antarctic Plateau. The aim was to measure for a full year, thus gaining a much-improved broader view of boundary layer ozone seasonality at different locations as well as of factors affecting the budget of surface ozone in Antarctica. Ozone mixing ratios were measured based on UV photometry using a modified version of the commercial 2B Technologies Inc. Model 202 instrument. All but one of the autonomous units measured successfully within its predefined duty cycle throughout the year, with some differences in performance dependent on power availability and ambient temperature. Mean data recovery after removal of outliers was on average 70% (range 44–83%) and precision varied between 1.5 and 8 ppbv, thus was sufficiently good to resolve year-round the main ozone features of scientific interest. We conclude that, with adequate power, and noting a minor communication problem, our units would be able to operate successfully at ambient temperatures down to −60 °C. Systems such as the one described in this paper, or derivatives of it, could therefore be deployed either as local or regional networks elsewhere in the Arctic or Antarctic. Here we present technical information and first results from the experiment.
Comparison of ground-based FTIR and Brewer O3 total column with data from two different IASI algorithms and from OMI and GOME-2 satellite instruments
Authors: Viatte C. , Schneider M. , Redondas A. , Hase F. , Eremenko M. , Chelin P. , Flaud J.-M. , Blumenstock T. , Orphal J.
Published: December 2010

Abstract. An intercomparison of ozone total column measurements derived from various platforms is presented in this work. Satellite data from Infrared Atmospheric Sounding Interferometer (IASI), Ozone Monitoring Instrument (OMI) and Global Ozone Monitoring Experiment (GOME-2) are compared with data from two ground-based spectrometers (Fourier Transform Infrared spectrometer FTIR and Brewer), located at the Network for Detection of Atmospheric Composition Change (NDACC) super-site of Izaña (Tenerife), measured during a campaign from March to June 2009. These ground-based observing systems have already been demonstrated to perform consistent, precise and accurate ozone total column measurements. An excellent agreement between ground-based and OMI/GOME-2 data is observed. Results from two different algorithms for deriving IASI ozone total column are also compared: the European Organisation for the Exploitation of Meteorological Satellites (EUMETSAT/ESA) operational algorithm and the LISA (Laboratoire Interuniversitaire des Systèmes Atmosphériques) algorithm. A better agreement was found with LISA's analytical approach based on an altitude-dependent Tikhonov-Philips regularization: correlations are 0.94 and 0.89 compared to FTIR and Brewer, respectively; while the operational IASI ozone columns (based on neural network analysis) show correlations of 0.90 and 0.85, respectively, compared to the O3 columns obtained from FTIR and Brewer.
Rapid accretion of dissolved organic carbon in the springs of Florida: the most organic-poor natural waters
Authors: Duarte C. M. , Prairie Y. T. , Frazer T. K. , Hoyer M. V. , Notestein S. K. , Martínez R. , Dorsett A. , Canfield D. E.
Published: December 2010

Abstract. The concentration of dissolved organic carbon (DOC) in groundwater emanating as spring discharge at several locations in Florida, USA and the net increase in DOC in the downstream receiving waters were measured as part of a larger investigation of carbon dynamics in flowing waters. Springs with high discharge (>2.8 m3 s−1) were found to be the most organic-poor natural waters yet reported (13 ± 1.6 μmol C L−1), while springs with lesser discharge exhibited somewhat higher DOC concentrations (values ranging from 30 to 77 μmol C L−1). DOC concentrations increased rapidly downstream from the point of spring discharge, with the calculated net areal input rate of DOC ranging from 0.04 to 1.64 mol C m−2 d−1 across springs. Rates of DOC increase were generally greater in those springs with high discharge rates. These input rates compare favorably with values reported for gross primary production in these macrophyte-dominated spring systems, assuming that 17% of macrophyte primary production is lost, on average, as DOC. The measures reported here are possible only because of the remarkably low DOC levels in the up-surging groundwaters and the short residency times of the water in the spring-runs themselves.