EL-hyperstructures: an overview

This paper gives a current overview of theoretical background of a special class of hyperstructures constructed from quasi / partially or dered (semi) groups using a construction known as the "Ends lemma". The paper is a collection of both older and new results presented at AHA 2011

A critical assessment of the nature, scope and adequacy of the Taliban and Al Qaeda sanctions regime(s) established by the United Nations Security Council

Alongside the development of methods of terrorism, society has developed ways of fighting it. This dissertation addresses modern forms of countering terrorism in the sense of sanctions regime(s) established by the United Nations Security Council. It is therefore primarily intended for people who already have some knowledge in this area and wish to explore this field further. This work is divided into three main sections. While relying largely, but not exclusively, on the Report of the National Commission on Terrorist Attacks Upon the United States and Steve Coll’s Ghost wars, the first section describes the circumstances under which the Taliban and al Qaeda formed and evolved. It also focuses on the motivations of the United Nations Security Council to impose targeted sanctions under Resolution 1267 (1999). Grasping the historical background is necessary for understanding the next section, which examines the core of the sanctions regime, particularly its general idea, structure and processes that allow it to achieve its designated goals. Based on research findings and a wide range of relevant materials, the concluding section assesses the effectiveness of the sanctions regime as well as providing a view towards future challenges and prospects

Genetic background modifies neurodegeneration and neuroinflammation driven by misfolded human tau protein in rat model of tauopathy: implication for immunomodulatory approach to Alzheimer's disease

<p>Abstract</p> <p>Background</p> <p>Numerous epidemiological studies demonstrate that genetic background modifies the onset and the progression of Alzheimer's disease and related neurodegenerative disorders. The efficacious influence of genetic background on the disease pathway of amyloid beta has been meticulously described in rodent models. Since the impact of genetic modifiers on the neurodegenerative and neuroinflammatory cascade induced by misfolded tau protein is yet to be elucidated, we have addressed the issue by using transgenic lines expressing the same human truncated tau protein in either spontaneously hypertensive rat (SHR) or Wistar-Kyoto (WKY) genetic background.</p> <p>Methods</p> <p>Brains of WKY and SHR transgenic rats in the terminal stage of phenotype and their age-matched non-transgenic littermates were examined by means of immunohistochemistry and unbiased stereology. Basic measures of tau-induced neurodegeneration (load of neurofibrillary tangles) and neuroinflammation (number of Iba1-positive microglia, their activated morphology, and numbers of microglia immunoreactive for MHCII and astrocytes immunoreactive for GFAP) were quantified with an optical fractionator in brain areas affected by neurofibrillary pathology (pons, medulla oblongata). The stereological data were evaluated using two-way ANOVA and Student's t-test.</p> <p>Results</p> <p>Tau neurodegeneration (neurofibrillary tangles (NFTs), axonopathy) and neuroinflammation (microgliosis, astrocytosis) appeared in both WKY and SHR transgenic rats. Although identical levels of transgene expression in both lines were present, terminally-staged WKY transgenic rats displayed significantly lower final NFT loads than their SHR transgenic counterparts. Interestingly, microglial responses showed a striking difference between transgenic lines. Only 1.6% of microglia in SHR transgenic rats expressed MHCII in spite of having a robust phagocytic phenotype, whereas in WKY transgenic rats, 23.2% of microglia expressed MHCII despite displaying a considerably lower extent of transformation into phagocytic phenotype.</p> <p>Conclusions</p> <p>These results show that the immune response represents a pivotal and genetically variable modifying factor that is able to influence vulnerability to neurodegeneration. Therefore, targeted immunomodulation could represent a prospective therapeutic approach to Alzheimer's disease.</p

Novel mutations in the toll like receptor genes cause hyporesponsiveness to Mycobacterium avium subsp. paratuberculosis infection

Toll like receptors play a central role in the recognition of pathogen associated molecular patterns (PAMPs). Mutations in TLR1, TLR2 and TLR4 genes may change the PAMP reorganization ability which causes altered responsiveness to the bacterial pathogens. A case control study, performed to assess the association between TLR gene mutations and susceptibility to Mycobacterium avium subsp. paratuberculosis (MAP), revealed novel mutations (TLR1 - Ser150Gly and Val220Met; TLR2 - Phe670Leu) that hindered either PAMP recognition or further downstream TLR pathway activation. A cytokine expression experiments (IL-4, IL-8, IL-10, IL-12 and IFN-&#x3b3;) in the challenged mutant and wild type moDCs (mocyte derived dendritic cells) confirmed the negative impact of these mutations and altered TLR downstream activation. Further In silico analysis of the TLR1 and TLR4 ectodomains (ECD) revealed the polymorphic nature of the central ECD and irregularities in the central LRR motifs. The most critical positions that may alter the pathogen recognition ability of TLR were: the 9th amino acid position in LRR motif (TLR1, LRR10) and 4th residue downstream to LRR domain (exta LRR region of TLR4). The study describes novel mutations in the TLRs and presents their association with the MAP infection

Ten Years of Tau-Targeted Immunotherapy: The Path Walked and the Roads Ahead

Neurofibrillary pathology comprised of pathological tau protein is closely tied to a range of neurodegenerative disorders, the most common of which is Alzheimer’s disease. While they are individually rarer, a range of other disorders, the tauopathies (including Pick’s disease, progressive supranuclear palsy, corticobasal degeneration, primary progressive aphasia, and ∼50% of behavioral variant frontotemporal dementia cases) display pronounced underlying tau pathology. In all cases, the distribution and amount of tau pathology closely correlates with the severity and phenotype of cognitive impairment, and with the pattern and degree of brain atrophy. Successfully counteracting tau pathology is likely to halt or slow the progression of these debilitating disorders. This makes tau a target of prime importance, yet an elusive one. The diversity of the tau proteome and post-translational modifications, as well as pathophysiology of tau are reviewed. Beginning 2013, a range of tau-targeted immunotherapies have entered clinical development; these therapies, and their common themes and differences are reviewed. The manuscript provides an extensive discussion on epitope selection for immunotherapies against tau pathology, on immunological mechanisms involved in their action, and challenges such as immune senescence, vaccine design, or evolution of epitopes. Furthermore, we provide methodological recommendations for the characterization of active vaccines and antibodies, animal models, and the target itself – the diseased tau proteome

Evaluation of Effective Thermal Conductivities of Porous Textile Composites

An uncoupled multi-scale homogenization approach is used to estimate the effective thermal conductivities of plain weave C/C composites with a high degree of porosity. The geometrical complexity of the material system on individual scales is taken into account through the construction of a suitable representative volume element (RVE), a periodic unit cell, exploiting the information provided by the image analysis of a real composite system on every scale. Two different solution procedures are examined. The first one draws on the classical first order homogenization technique assuming steady state conditions and periodic distribution of the fluctuation part of the temperature field. The second approach is concerned with the solution of a transient flow problem. Although more complex, the latter approach allows for a detailed simulation of heat transfer in the porous system. Effective thermal conductivities of the laminate derived from both approaches through a consistent homogenization on individual scales are then compared with those obtained experimentally. A reasonably close agreement between individual results then promotes the use of the proposed multi-scale computational approach combined with the image analysis of real material systems.Comment: 17 pages, 7 figure

Folding of Alzheimer's core PHF subunit revealed by monoclonal antibody 423

AbstractAt present, the conformation-dependent monoclonal antibodies (mAb) provide the only information on folding of tau in the core PHF. Monoclonal antibody MN423 recognizes all and only those Alzheimer's disease (AD) core paired helical filaments (PHFs) subunits, which terminate at Glu391. Using recombinant analogs of the core PHF subunit corresponding to tau residues τ297–391, we found that the C-terminal pentapeptide 387DHGAE391 represented only one component of the structure recognized by mAb 423. Therefore, deletion mutants of the core subunit were generated to identify assembled parts of this conformational structure. We localized two spatially close components in the region 306–325 (306VQIVYK311 and 321KCGSL325) contributing to formation of the structure identified by mAb 423. Thus, the spatial proximity of three subunit segments 306VQIVYK311, 321KCGSL325 and 387DHGAE391 represents constraints for intramolecular folding of the core PHF subunit. Since PHF represents a compelling drug target in AD, structural knowledge presented could contribute to structure-based drug design

Operation and Planning of Energy Hubs Under Uncertainty - a Review of Mathematical Optimization Approaches

Co-designing energy systems across multiple energy carriers is increasingly attracting attention of researchers and policy makers, since it is a prominent means of increasing the overall efficiency of the energy sector. Special attention is attributed to the so-called energy hubs, i.e., clusters of energy communities featuring electricity, gas, heat, hydrogen, and also water generation and consumption facilities. Managing an energy hub entails dealing with multiple sources of uncertainty, such as renewable generation, energy demands, wholesale market prices, etc. Such uncertainties call for sophisticated decision-making techniques, with mathematical optimization being the predominant family of decision-making methods proposed in the literature of recent years. In this paper, we summarize, review, and categorize research studies that have applied mathematical optimization approaches towards making operational and planning decisions for energy hubs. Relevant methods include robust optimization, information gap decision theory, stochastic programming, and chance-constrained optimization. The results of the review indicate the increasing adoption of robust and, more recently, hybrid methods to deal with the multi-dimensional uncertainties of energy hubs

Neuropsychological Functioning and Temperament Traits in a Czech Sample of Children and Adolescents at Familial Risk of Bipolar Disorder

Background: Although a positive family history is the strongest predictor for bipolar disorder (BD), most offspring of BD parents (BO) will not develop the disorder. Identification of vulnerability markers for BD is essential for specific individual risk estimation. Impairments in cognitive functioning and the presence of specific temperament traits are considered promising candidates.Methods: Sixty-three BO (48% female; 11.8 ± 3.3 years) and 54 control offspring (CO; 44% female; 12.3 ± 3.2 years) comparable in sex (p = 0.4) and age (p = 0.4) were enrolled. Detection of current sub/threshold mood symptoms by the Kiddie Schedule for Affective Disorders and Schizophrenia and General Behavior Inventory was applied to separate BO into ultrahigh-risk (UHR) and high-risk (HR) subgroups. Cognitive functions were tested by the Developmental Neuropsychological Assessment II test battery, d2 Test of Attention, and Amsterdam Neuropsychological Tasks. Temperament was assessed by the Temperament in Middle Childhood and Early Adolescent Temperament Questionnaires.Results: The BO sample consisted of 5 BD, 17 UHR, and 41 HR participants. We did not observe any significant differences between the BO and CO groups or between the UHR, HR, and CO subgroups (Hedges' g = 0.21–0.39) in cognitive functioning. The BO differed significantly in some temperament traits from the CO (g = 0.42–0.61), while the UHR subgroup exhibited lower effortful control and attention focusing than both HR and CO participants (g = 0.92–1.19).Limitations: The cross-sectional design and wide age range of the sample limited our findings.Conclusions: Neuropsychological impairment does not seem to be a trait marker of BD in the premorbid stage. Temperament with low effortful control and low attention focusing might be associated with the development of mood disorders in BO