A critical analysis of the 'amyloid cascade hypothesis'

The 'amyloid cascade hypothesis' (ACH) is the most influential model of the pathogenesis of Alzheimer's disease (AD). The hypothesis proposes that the deposition of β-amyloid (Aβ) is the initial pathological event in AD, leading to the formation of extracellular senile plaques (SP), tau-immunoreactive neurofibrillary tangles (NFT), neuronal loss, and ultimately, clinical dementia. Ever since the formulation of the ACH, however, there have been questions regarding whether it completely describes AD pathogenesis. This review critically examines various aspects of the ACH including its origin and development, the role of amyloid precursor protein (APP), whether SP and NFT are related to the development of clinical dementia, whether Aβ and tau are 'reactive' proteins, and whether there is a pathogenic relationship between SP and NFT. The results of transgenic experiments and treatments for AD designed on the basis of the ACH are also reviewed. It was concluded: (1) Aβ and tau could be the products rather than the cause of neuro-degeneration in AD, (2) it is doubtful whether there is a direct causal link between Aβ and tau, and (3) SP and NFT may not be directly related to the development of dementia, (4) transgenic models involving APP alone do not completely replicate AD pathology, and (5) treatments based on the ACH have been unsuccessful. Hence, a modification of the ACH is proposed which may provide a more complete explanation of the pathogenesis of AD.

Global Results for Solution to the Mass-Critical Schrödinger Equation with Convolution Nonlinearity in R^n

Георги Венков, Христо Генев - Разглеждаме един клас от L^2 - критични нелинейни уравнения на Шрьодингер в R^(1+n) с конволюционна нелинейност от тип Хартри. Целта ни е да установим локалното и глобално съществуване на решенията, както и коректност на задачата на Коши в достатъчно малка околност на нулата в пространството L^2 (R^n). Като естествено следствие на глобалните резултати ние доказваме съществуване на оператор на разсейване за малки начални условия.

On the Critical Points of Kyurkchiev’s Method for Solving Algebraic Equations

This paper is dedicated to Prof. Nikolay Kyurkchiev on the occasion of his 70th anniversary This paper gives sufficient conditions for kth approximations of the zeros of polynomial f (x) under which Kyurkchiev’s method fails on the next step. The research is linked with an attack on the global convergence hypothesis of this commonly used in practice method (as correlate hypothesis for Weierstrass–Dochev’s method). Graphical examples are presented.

The refinement and validation of the critical decision making and problem solving scale moral dilema (CDP-MD)

This thesis extended previous research on critical decision making and problem solving by refining and validating a measure designed to assess the use of critical thinking and critical discussion in sociomoral dilemmas. The purpose of this thesis was twofold: 1) to refine the administration of the Critical Thinking Subscale of the CDP to elicit more adequate responses and for purposes of refining the coding and scoring procedures for the total measure, and 2) to collect preliminary data on the initial reliabilities of the measure. Subjects consisted of 40 undergraduate students at Florida International University. Results indicate that the use of longer probes on the Critical Thinking Subscale was more effective in eliciting adequate responses necessary for coding and evaluating the subjects performance. Analyses on the psychometric properties of the measure consisted of test-retest reliability and inter-rater reliability.

Geometric inequalities for initial data with symmetries

We consider a class of initial data sets (Σ,h,K) for the Einstein constraint equations which we define to be generalized Brill (GB) data. This class of data is simply connected, U(1)²-invariant, maximal, and four-dimensional with two asymptotic ends. We study the properties of GB data and in particular the topology of Σ. The GB initial data sets have applications in geometric inequalities in general relativity. We construct a mass functional M for GB initial data sets and we show:(i) the mass of any GB data is greater than or equals M, (ii) it is a non-negative functional for a broad subclass of GB data, (iii) it evaluates to the ADM mass of reduced t − φi symmetric data set, (iv) its critical points are stationary U(1)²-invariant vacuum solutions to the Einstein equations. Then we use this mass functional and prove two geometric inequalities: (1) a positive mass theorem for subclass of GB initial data which includes Myers-Perry black holes, (2) a class of local mass-angular momenta inequalities for U(1)²-invariant black holes. Finally, we construct a one-parameter family of initial data sets which we show can be seen as small deformations of the extreme Myers- Perry black hole which preserve the horizon geometry and angular momenta but have strictly greater energy.

On the Initial Stages of the Densification and Lithification of Sediments

Peer reviewed

On the Initial Stages of the Densification and Lithification of Sediments

Peer reviewed

Early Years Teachers and young children’s rights: the need for critical dialogue

The absence of knowledge about children’s rights is frequently associated with ineffective implementation of the United Nations Convention on the Rights of the Child (UNCRC); this directly impacts on children’s lives and the ways they are viewed by adults (Freeman 1998; Pugh 2015). Recent research (Jerome et al. 2015) has highlighted the lack of focus on children’s rights in the initial training of teachers and other education practitioners. In this paper I analyse the status of children’s rights in the standards for Early Years Teachers (EYTs) introduced in 2013 in England. Informed by the findings from research in sites of early years practice, I suggest possibilities for a critical dialogue that repositions the UNCRC as a visible and explicit framework of reference for EYTs’ work with young children.

Applications for nanomaterials in critical technologies

This thesis is devoted to the development, synthesis, properties, and applications of nano materials for critical technologies, including three areas: (1) Microbial contamination of drinking water is a serious problem of global significance. About 51% of the waterborne disease outbreaks in the United States can be attributed to contaminated ground water. Development of metal oxide nanoparticles, as viricidal materials is of technological and fundamental scientific importance. Nanoparticles with high surface areas and ultra small particle sizes have dramatically enhanced efficiency and capacity of virus inactivation, which cannot be achieved by their bulk counterparts. A series of metal oxide nanoparticles, such as iron oxide nanoparticles, zinc oxide nanoparticles and iron oxide-silver nanoparticles, coated on fiber substrates was developed in this research for evaluation of their viricidal activity. We also carried out XRD, TEM, SEM, XPS, surface area measurements, and zeta potential of these nanoparticles. MS2 virus inactivation experiments showed that these metal oxide nanoparticle coated fibers were extremely powerful viricidal materials. Results from this research suggest that zinc oxide nanoparticles with diameter of 3.5 nm, showing an isoelectric point (IEP) at 9.0, were well dispersed on fiberglass. These fibers offer an increase in capacity by orders of magnitude over all other materials. Compared to iron oxide nanoparticles, zinc oxide nanoparticles didn’t show an improvement in inactivation kinetics but inactivation capacities did increase by two orders of magnitude to 99.99%. Furthermore, zinc oxide nanoparticles have higher affinity to viruses than the iron oxide nanoparticles in presence of competing ions. The advantages of zinc oxide depend on high surface charge density, small nanoparticle sizes and capabilities of generating reactive oxygen species. The research at its present stage of development appears to offer the best avenue to remove viruses from water. Without additional chemicals and energy input, this system can be implemented by both points of use (POU) and large-scale use water treatment technology, which will have a significant impact on the water purification industry. (2) A new family of aliphatic polyester lubricants has been developed for use in micro-electromechanical systems (MEMS), specifically for hard disk drives that operate at high spindle speeds (>15000rpm). Our program was initiated to address current problems with spin-off of the perfluoroether (PFPE) lubricants. The new polyester lubricant appears to alleviate spin-off problems and at the same time improves the chemical and thermal stability. This new system provides a low cost alternative to PFPE along with improved adhesion to the substrates. In addition, it displays a much lower viscosity, which may be of importance to stiction related problems. The synthetic route is readily scalable in case additional interest emerges in other areas including small motors. (3) The demand for increased signal transmission speed and device density for the next generation of multilevel integrated circuits has placed stringent demands on materials performance. Currently, integration of the ultra low-k materials in dual Damascene processing requires chemical mechanical polishing (CMP) to planarize the copper. Unfortunately, none of the commercially proposed dielectric candidates display the desired mechanical and thermal properties for successful CMP. A new polydiacetylene thermosetting polymer (DEB-TEB), which displays a low dielectric constant (low-k) of 2.7, was recently developed. This novel material appears to offer the only avenue for designing an ultra low k dielectric (1.85k), which can still display the desired modulus (7.7Gpa) and hardness (2.0Gpa) sufficient to withstand the process of CMP. We focused on further characterization of the thermal properties of spin-on poly (DEB-TEB) ultra-thin film. These include the coefficient of thermal expansion (CTE), biaxial thermal stress, and thermal conductivity. Thus the CTE is 2.0*10-5K-1 in the perpendicular direction and 8.0*10-6 K-1 in the planar direction. The low CTE provides a better match to the Si substrate which minimizes interfacial stress and greatly enhances the reliability of the microprocessors. Initial experiments with oxygen plasma etching suggest a high probability of success for achieving vertical profiles.

The challenges of integrating the discussion of controversial issues in initial teacher training

In the framework of the Bologna process, and with regard to pre-service teacher education, it is necessary to model student-centred learning experiences in order to promote the required competences for future professional practice and critical participation in society. Despite the potential of discussion in promoting several competences, this methodology does not always integrate the teaching practices. This case study sought to: a) understand the experiences and views of future teachers from a School of Education on the use of discussion in their past education; and b) investigate the impact of an educational experience centred on discussion. Data were collected through narratives, questionnaires, interviews and participant observation. The learning situations experienced through this study contributed to the development of citizens more aware of their role in society and allowed the promotion of skills indispensable for an Elementary Education teacher.

The challenges of integrating the discussion of controversial issues in initial teacher training

In the framework of the Bologna process, and with regard to pre-service teacher education, it is necessary to model student-centred learning experiences in order to promote the required competences for future professional practice and critical participation in society. Despite the potential of discussion in promoting several competences, this methodology does not always integrate the teaching practices. This case study sought to: a) understand the experiences and views of future teachers from a School of Education on the use of discussion in their past education; and b) investigate the impact of an educational experience centred on discussion. Data were collected through narratives, questionnaires, interviews and participant observation. The learning situations experienced through this study contributed to the development of citizens more aware of their role in society and allowed the promotion of skills indispensable for an Elementary Education teacher.

Acute Q Fever Presenting with Multi-Organ Failure: Re-Evaluation of the Initial Diagnosis

We present the case of a 48-year-old man admitted to the critical care unit with atrial fibrillation, and acute heart and kidney failure accompanied by coagulopathy and an abnormal liver test. Initially diagnosed as a non-ST elevation myocardial infarction, re-evaluation of the case led to the consideration of severe sepsis. Q fever and leptospirosis were the most probable causes and empiric treatment was initiated. A complete recovery was achieved following treatment.

Initial public offering

O presente relatório foi realizado no âmbito do estágio curricular do Mestrado em Análise Financeira do Instituto Superior de Contabilidade e Administração de Coimbra que decorreu na Critical Software S.A, na sua sede, em Taveiro, Coimbra. O relatório divide-se que três partes, nomeadamente, na caracterização da entidade de acolhimento e descrição das actividades desenvolvidas, no estudo da possibilidade de entrada em bolsa de valores da Critical Software e por último algumas notas conclusivas do tema apresentado. Os objectivo deste relatório consiste no estudo da Oferta Publica Inicial (Initial Public Oferring) aplicada à Critical Software, ou seja, pretendo analisar se a operação é vantajosa para a empresa e explanar as vantagens e desvantagens que advém desta operação. Este relatório explica as diversas exigências, procedimentos e custos que esta operação acarreta para a empresa.