1,524 research outputs found
Therapeutic strategies in Parkinson's disease: what we have learned from animal models
No full textParkinson’s disease (PD), the second most common neurodegenerative disorder, is characterized by a loss of dopamin-ergic neurons in the substantia nigr a, as well as in other brain areas. The currently available dopamine replacement therapy provides merely sy mptomatic benefit and is ineffective because habituation and side effects arise relatively quickly. Studying the genetic forms of PD in animal models provides novel insight that allows targeting of specific aspects of this heterogenic disease more specifically. Among others, two important cellular deficits are associated with PD; these deficits relate to (1) synaptic transmission and vesicle trafficking, and (2) mitochondr ial function, relating respectively to the dominant and recessive mutations in PD-causing genes. With increased knowledge of PD, the possibility of identifying an efficient, long-lasting treatment is becoming more conceivable, but this can only be done with an increased knowledge of the specific affected cellular mechanisms. This review discusses how discoveries in animal models of PD have clarified the therapeutic potential of pathways disrupted in PD, w ith a specific focus on synaptic transmission, vesicle trafficking, and mitochondrial function.sponsorship: European Research Council, KU Leuven, Fonds Wetenschappelijk Onderzoek, Fundação para a Ciência e a Tecnologia (FCT), Interuniversitaire Attractie Pool (IAP) by the Belgian Science Policy (BELSPO), Instituut voor Wetenschap en Technologie (IWT), VIB, Methusalem grant of the Flemish government, Hercules Foundationstatus: Publishe
Accelerated norm-optimal iterative learning control
No full textThis paper proposes a novel technique for accelerating the convergence of the previously published norm-optimal iterative learning control (NOILC) methodology. The basis of the results is a formal proof of an observation made by the first author, namely that the NOILC algorithm is equivalent to a successive projection algorithm between linear varieties in a suitable product Hilbert space. This leads to two proposed accelerated algorithms together with well-defined convergence properties. The results show that the proposed accelerated algorithms are capable of ensuring monotonic error norm reductions and can outperform NOILC by more rapid reductions in error norm from iteration to iteration. In particular, examples indicate that the approach can improve the performance of NOILC for the problematic case of non-minimum phase systems. Realisation of the algorithms is discussed and numerical simulations are provided for comparative purposes and to demonstrate the numerical performance and effectiveness of the proposed methods
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The Life and Work of D.H. Hyers, 1913-1997
No full textThe following is a sketch of the life and work of Donald Holmes Hyers, Professor Emeritus from the University of Southern California. The theorem put forth by Hyers in 1941 concerning linear functional equations has gained a great deal of interest over the past two decades. Hundreds of articles have been written citing his works, many of which have furthered the theorem. This paper contains a brief description of Hyers’ theorem, a biographical essay and an extensive bibliography of Hyers’ work and works citing the Hyers theorem or the D.H. Hyers–S.M. Ulam–Th.M. Rassias theorem or related subjects of almost the last three decades. The author of this paper is the grandson of D.H. Hyers
Functional genomic analysis of frataxin deficiency reveals tissue-specific alterations and identifies the PPAR{gamma} pathway as a therapeutic target in Friedreich's ataxia.
No full textFriedreich's ataxia (FRDA), the most common inherited ataxia, is characterized by focal neurodegeneration, diabetes mellitus, and life-threatening cardiomyopathy. Frataxin, which is significantly reduced in patients with this recessive disorder, is a mitochondrial iron-binding protein, but how its deficiency leads to neurodegeneration and metabolic derangements is not known. We performed microarray analysis of heart and skeletal muscle in a mouse model of frataxin deficiency, and found molecular evidence of increased lipogenesis in skeletal muscle, and alteration of fiber-type composition in heart, consistent with insulin resistance and cardiomyopathy, respectively. Since the peroxisome proliferator-activated receptor gamma (PPARgamma) pathway is known to regulate both processes, we hypothesized that dysregulation of this pathway could play a key role in frataxin deficiency. We confirmed this by showing a coordinate dysregulation of the PPARgamma coactivator Pgc1a and transcription factor Srebp1 in cellular and animal models of frataxin deficiency, and in cells from FRDA patients, who have marked insulin resistance. Finally, we show that genetic modulation of the PPARgamma pathway affects frataxin levels in vitro, supporting PPARgamma as a novel therapeutic target in FRDA
The treatment of Italy and Italians in D.H. Lawrence's writings
No full textThis thesis was scanned from the print manuscript for digital preservation and is copyright the author.
Researchers can access this thesis by asking their local university, institution or public library to
make a request on their behalf. Monash staff and postgraduate students can use the link in the References field
Environmental (waste) compliance control systems for UK SMEs
No full textWhile the ‘environment’ is often perceived as a heavily regulated area of business, in reality, directly-regulated businesses represent a small proportion of the business community. This study aimed to evaluate and outline potential improvements to compliance controls for small and medium-sized enterprises (SMEs), particularly those involved in the waste sector. Forty-four SMEs from England were interviewed/audited between April-September 2008. Using a UK-based system as a case-in-point, the Environment Agency’s (EA) Operational Risk Appraisal (‘Opra’)/Compliance Assessment Report (CAR) system was analysed. Environmental compliance performance indicators and an initial assessment methodology for SMEs were developed. The study showed:• Compliance with permitting legislation was poor in many areas.• Regulatory authorities are either unable/failing to implement their enforcement policies or unable/failing to identify non-compliances due to the infrequency or limited nature of their inspections.• Improvements are needed to the EA Opra/CAR system – control measures are not fully taken into account when calculating risk.Recommendations to improve SME compliance controls include using internationally applicable general and specific compliance and non-compliance performance indicators, re-designing the Opra system and using an initial assessment methodology based on understanding the hazardousness of SME categories, compliance levels and operator competency.<br/
The Importance Of Sex In Marriage Reflected In D.H. Lawrence’s Lady Chatterley’s Lover Novel (1928): A Psychoanalytic Perspective
No full textThis study is about the importance of sex in marriage in Lady Chatterley’s Lover. The objectives of the study are conducted to identify the indicators of the need for sex of the major character, to describe the major character attempt to meet the need, and to reveal the underlying reason of why the major character did viewed from the psychoanalytic perspective. The object of the study is Lady Chatterley’s Lover by D.H. Lawrence. It used psychoanalytic perspective. This research is a descriptive qualitative research. The type of data in this study is a text that consists of words, phrases and sentences. There are two data sources in this study. The primary data source is Lady
Chatterley’s Lover by D.H. Lawrence. The secondary data source consists of the other data, which have a relationship with the study, such as some biography of
the author, and other relevant information. The result of the study shows the following conclusions. First, based on the structural analysis the author wants to deliver a message that the meeting of sexual need is important in marriage. Second, based on the psychoanalytic perspective, it clear that in this novel D.H. Lawrence describes psychological phenomena in which one is seeking for the sexual satisfaction from a person other than one‟s spouse
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