Identification of true microstructure of composites based on various flax fibre assemblies by means of three-dimensional tomography

Lately it has been demonstrated that natural fibres may be an environmentally superior alternative for, e.g., glass fibres. In order to estimate properties of composite materials made of natural fibres, models designed for synthetic fibres are often used. The models usually do not account for irregularities in the material, e.g., suboptimal fibre orientation due to the twisting angle of fibres in yarns. Use of models without taking those features into account might lead to unreliable results. Methods to quantify the microstructural properties of natural fibre composites with X-ray microtomography and three-dimensional image analysis are demonstrated in this work. The methods are applied to flax fibre composites made from three different kinds of pre-forms. Microstructural parameters estimated with the methods are used in micromechanical models for the stiffness of the composite. Comparison between rule-of-mixtures and classical laminate theory is made, highlighting the requirement for accurate parameter estimation and use of a model that accounts for significant structural features of the material.Godkänd; 2015; 20150818 (joffe

Mildronate and its Neuroregulatory Mechanisms : Targeting the Mitochondria, Neuroinflammation, and Protein Expression

This review for the first time summarizes the data obtained in the neuropharmacological studies of mildronate, a drug previously known as a cardioprotective agent. In different animal models of neurotoxicity and neurodegenerative diseases, we demonstrated its neuroprotecting activity. By the use of immunohistochemical methods and Western blot analysis, as well as some selected behavioral tests, the new mechanisms of mildronate have been demonstrated: a regulatory effect on mitochondrial processes and on the expression of nerve cell proteins, which are involved in cell survival, functioning, and inflammation processes. Particular attention is paid to the capability of mildronate to stimulate learning and memory and to the expression of neuronal proteins involved in synaptic plasticity and adult neurogenesis. These properties can be useful in neurological practice to protect and treat neurological disorders, particularly those associated with neurodegeneration and a decline in cognitive functions.publishersversionPeer reviewe

Mildronate's protective effects in the peripheral nervous system : Stavudine-induced neuropathy and formalin-induced inflammation

Funding Information: This work was supported by the Latvian Council of Science Grant Nr. 05-1418; ESF Grant ESS2004/3; Contract No. 453, between the Latvian Institute of Organic Synthesis and the Joint Stock Company “Grindex”; Contract No. 2377, between the University of Latvia and the Joint Stock Company “Grindex”; and a L’ORÉAL Latvian “For Women In Science” fellowship with the support of the Latvian National Commission for UNESCO and the Latvian Academy of Sciences.Mildronate, previously known as a cardioprotective drug, recently was found to normalise mitochondrial processes by preventing the dysfunction of complex I in rat liver mitochondria. Previously we have shown also the ability of mildronate to prevent pathologies in the central nervous system by normalizing the expression of different signalling molecules in brain tissue. This allowed us to suggest that mildronate may possess a beneficial role also in peripheral nervous system pathologies. The present study was designed to assess the peripheral tissue damage caused by anti-HIV drug stavudine, as well as pain and inflammation caused by formalin. For this demonstration, we investigated the influence of mildronate: (1) on decreased myelin expression and increased neuron degeneration in rat sciatic nerve tissue caused by stavudine; and (2) on formalin-induced inflammation in mice. We found that mildronate protected the stavudine-induced degeneration of neurons in rat peripheral sciatic nerve without a significant influence on demyelination. In a formalin test, mildronate showed anti-inflammatory action comparable to that of indomethacin, a reference drug. The present results show that mildronate is capable of regulating peripheral nerve damage and peripheral inflammatory responses. We suggest that the multifunctional effects of mildronate can be attributed to its ability to regulate mitochondrial processes. The obtained data indicate protective effects of mildronate in different peripheral neurological pathologies.publishersversionPeer reviewe

Neuroprotective Properties of Mildronate, a Small Molecule, in a Rat Model of Parkinson’s Disease

Previously, we have found that mildronate [3-(2,2,2-trimethylhydrazinium) propionate dihydrate], a small molecule with charged nitrogen and oxygen atoms, protects mitochondrial metabolism that is altered by inhibitors of complex I and has neuroprotective effects in an azidothymidine-neurotoxicity mouse model. In the present study, we investigated the effects of mildronate in a rat model of Parkinson’s disease (PD) that was generated via a unilateral intrastriatal injection of the neurotoxin 6-hydroxydopamine (6-OHDA). We assessed the expression of cell biomarkers that are involved in signaling cascades and provide neural and glial integration: the neuronal marker TH (tyrosine hydroxylase); ubiquitin (a regulatory peptide involved in the ubiquitin-proteasome degradation system); Notch-3 (a marker of progenitor cells); IBA-1 (a marker of microglial cells); glial fibrillary acidic protein, GFAP (a marker of astrocytes); and inducible nitric oxide synthase, iNOS (a marker of inflammation). The data show that in the 6-OHDA-lesioned striatum, mildronate completely prevented the loss of TH, stimulated Notch-3 expression and decreased the expression of ubiquitin, GFAP and iNOS. These results provide evidence for the ability of mildronate to control the expression of an array of cellular proteins and, thus, impart multi-faceted homeostatic mechanisms in neurons and glial cells in a rat model of PD. We suggest that the use of mildronate provides a protective effect during the early stages of PD that can delay or halt the progression of this neurodegenerative disease

Very low doses of muscimol and baclofen ameliorate cognitive deficits and regulate protein expression in the brain of a rat model of streptozocin-induced Alzheimer's disease

Recent studies devoted to neuroprotection have focused on the role of the gamma-aminobutyric acid (GABA) system in regulating neuroinflammatory processes which play a key role in the neurodegenerative processes observed in Alzheimer's disease (AD) by inducing glial cell overactivation and impairing neurotransmission. Data on the efficacy of classical GABA-A and GABA-B receptor agonists (muscimol and baclofen, respectively) in animal models of AD are not available. Moreover, no published studies have examined the ability of optimal doses of these compounds to prevent neuroinflammation, the alterations in neurotransmission and cognitive deficits. In the present study, we used a non-transgenic rat model of AD obtained by intracerebroventricular streptozocin (STZ) injection and assessed the effects of muscimol and baclofen at very low doses (0.01-0.05mg/kg) on spatial memory and the expression of cortical and hippocampal proteins related to neuroinflammation, namely proteins involved in astroglial functions (glial fibrillary acidic protein, GFAP), GABA synthesis (GABA synthesizing enzyme, glutamic acid decarboxylase 67, GAD67) and acetylcholine degradation (acetylcholine esterase). The presented study demonstrated that in a rat model of STZ-induced AD both muscimol and baclofen at the tested doses exerted memory-enhancing and anti-inflammatory effects, as well as normalization of acetylcholine esterase and GABA expression. We suggested that the function of very low doses of GABA receptor agonists differs from typical GABA-related inhibition and may be mediated by the allosteric sites of GABA receptors or other non-specific cell regulatory pathways

Intranasal Administration of Extracellular Vesicles Derived from Human Teeth Stem Cells Improves Motor Symptoms and Normalizes Tyrosine Hydroxylase Expression in the Substantia Nigra and Striatum of the 6-Hydroxydopamine-Treated Rats

Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting millions of people worldwide. At present, there is no effective cure for PD; treatments are symptomatic and do not halt progression of neurodegeneration. Extracellular vesicles (EVs) can cross the blood–brain barrier and represent promising alternative to the classical treatment strategies. In the present study, we examined therapeutic effects of intranasal administration of EVs derived from human exfoliated deciduous teeth stem cells (SHEDs) on unilateral 6‐hydroxydopamine (6‐OHDA) medial forebrain bundle (MFB) rat model of PD. CatWalk gait tests revealed that EVs effectively suppressed 6‐OHDA‐induced gait impairments. All tested gait parameters (stand, stride length, step cycle, and duty cycle) were significantly improved in EV‐treated animals when compared with 6‐OHDA‐lesion group rats. Furthermore, EVs slowed down numbers of 6‐OHDA‐induced contralateral rotations in apomorphine test. Improvements in motor function correlated with normalization of tyrosine hydroxylase expression in the striatum and substantia nigra. In conclusion, we demonstrated, for the first time, the therapeutic efficacy of intranasal administration of EVs derived from SHEDs in a rat model of PD induced by 6‐OHDA intra‐MFB lesion. Our findings could be potentially exploited for the development of new treatment strategies against PD

The EC4 European syllabus for post-graduate training in clinical chemistry and laboratory medicine : Version 4-2012

Laboratory medicine’s practitioners across the European community include medical, scientific and pharmacy trained specialists whose contributions to health and healthcare is in the application of diagnostic tests for screening and early detection of disease, differential diagnosis, monitoring, management and treatment of patients, and their prognostic assessment. In submitting a revised common syllabus for post-graduate education and training across the 27 member states an expectation is set for harmonised, high quality, safe practice. In this regard an extended ‘Core knowledge, skills and competencies’ division embracing all laboratory medicine disciplines is described. For the first time the syllabus identifies the competencies required to meet clinical leadership demands for defining, directing and assuring the efficiency and effectiveness of laboratory services as well as expectations in translating knowledge and skills into ability to practice. In a ‘Specialist knowledge’ division, the expectations from the individual disciplines of Clinical Chemistry/Immunology, Haematology/Blood Transfusion, Microbiology/ Virology, Genetics and In Vitro Fertilisation are described. Beyond providing a common platform of knowledge, skills and competency, the syllabus supports the aims of the European Commission in providing safeguards to increasing professional mobility across European borders at a time when demand for highly qualified professionals is increasing and the labour force is declining. It continues to act as a guide for the formulation of national programmes supplemented by the needs of individual country priorities.peer-reviewe

Non-linear model applied on composites exhibiting inelastic behavior: development and validation

The polymeric composite materials are in high demand by industries where light and strong materials are required. Although manmade fiber (e.g. glass, carbon, aramid fibers) are most often used to reinforce polymers, natural fibers due to their environmental friendliness and sustainability have been also considered. Natural fiber composites have shown to have great potential as a substitute for conventional glass fiber materials. However, bio-based composites exhibit highly non-linear behavior, besides they are very sensitive to elevated moisture and temperature. Therefore, careful design and optimization of composite properties defined by constituents, composition and internal structure is needed to meet requirements of real-life applications. This can be done by using accurate models that can take into account factors responsible for inelastic behavior of these materials. The initial part of this thesis is dealing with development of phenomenological approach to predict inelastic behavior of composites in tension. Viscoelasticity and viscoplasticity was analyzed in short term creep tests and modulus degradation in stiffness degradation tests. Schapery’s model for viscoelasticity and Zapa’s model for viscoplasticity was used to characterize nonlinearity. This method was then validated on short, randomly oriented fiber composites with different cellulosic fibers (flax, viscose) and bio-polymers (PLA, Lignin). The elastic modulus, tensile stress-strain curves and failure were analyzed at different humidity and temperature levels. Results showed high sensitivity to moisture and temperature and highly non-linear behavior of these materials. Modeling showed good agreement between experimental data and simulations.Since there is need for simulations of strain controlled tests, this model was rewritten in inverted incremental form. Simulations of stress-strain curves showed, that predictions are more accurate, when characterization of viscoelastic and viscoplastic parameters was done at stresses close to failure. However, due to creep rapture it was not always possible to characterize material at high stresses and in this case viscoelastic functions have to be extrapolated. The stress-strain curves can be then used to further adjust extrapolation of model parameters.The model developed in the first part of the thesis proved to be capable of predicting behavior of short fiber composites with good accuracy. However, in order to carry out simulations input parameters have to be experimentally obtained and it has to be done for every composite that is studied. The second part of this thesis is dedicated to development of constitutive model which uses parameters of constituents to predict behavior of material with any composition. This model then is applied on semi-structural natural fiber composites consisting of bio-based resins reinforced with continuous cellulosic fibers. Mechanical properties of different bio-based thermoset resins and regenerated cellulose fibers have been analyzed. Results showed comparable properties of bio-based and synthetic epoxy resins, even at elevated humidity levels, but high scattering of properties from sample to sample. They also showed that bio-based resin exhibit limited non-linearity whereas regenerated cellulose fiber is highly non-linear.In order to avoid large scatter typical for bio-based materials and improve accuracy of the model, methodology for parameter identification for viscoplastic model with use of only one sample has been suggested.The objective here is to simulate strain controlled tests and the most convenient way to do it is with Schapery’s strain formulation model. The parameters for such model can be obtained from relaxation tests, where viscoelastic strain is kept constant but due to presence of viscoplastic strain component such experiments are difficult to perform. Instead, constituents exhibiting viscoplastic behavior have been characterized in creep and viscoelastic parameters for Schapery’s strain formulation are obtained from simulations of relaxation tests with inverted incremental model. Then these parameters are used to simulate behavior of composite subjected to iso-strain conditions.Godkänd; 2015; 20150315 (livroz); Nedanstående person kommer att disputera för avläggande av teknologie doktorsexamen. Namn: Liva Pupure Ämne: Polymera konstruktionsmaterial/Polymeric Composite Materials Avhandling: Non-linear Model Applied on Composites Exhibiting Inelastic Behavior: Development and Validation Opponent: Industrial Assistant professor Maciej Wysocki, Chalmers tekniska högskola, Göteborg/Scientific Coordinator Leader Swerea SICOMP, Mölndal Ordförande: Professor Roberts Joffe, Avdelningen för materialvetenskap, Institutionen för teknikvetenskap och matematik, Luleå tekniska universitet, Luleå Tid: Fredag 17 april kl 10.00 Plats: E246, Luleå tekniska universite