An in vitro study of osteoblast vitality influenced by the vitamins C and E

Vitamin C and vitamin E are known as important cellular antioxidants and are involved in several other non-antioxidant processes. Generally vitamin C and vitamin E are not synthesized by humans and therefore have to be applied by nutrition. The absence or deficiency of the vitamins can lead to several dysfunctions and even diseases (e.g. scurvy). The main interest in this study is that vitamin C and E are known to influence bone formation, e.g. vitamin C plays the key role in the synthesis of collagen, the major component of the extracellular bone matrix. In the present study we evaluate the effect of ascorbic acid (vitamin C) and α-tocopherol (vitamin E) on the proliferation and differentiation of primary bovine osteoblasts in vitro. Starting from standard growth medium we minimized the foetal calf serum to reduce their stimulatory effect on proliferation. An improved growth and an increased synthesis of the extracellular matrix proteins collagen type I, osteonectin and osteocalcin was observed while increasing the ascorbic acid concentration up to 200 μg/ml. Furthermore the effects of α-tocopherol on cell growth and cell differentiation were examined, whereby neither improved growth nor increased synthesis of the extracellular matrix proteins collagen type I, osteonectin and osteocalcin were detected. Further investigations are necessary to target at better supportive effect of vitamins on bone regeneration, and healing

Unfolded Protein Response Activation Reduces Secretion and Extracellular Aggregation of Amyloidogenic Immunoglobulin Light Chain

Light-chain amyloidosis (AL) is a degenerative disease characterized by the extracellular aggregation of a destabilized amyloidogenic Ig light chain (LC) secreted from a clonally expanded plasma cell. Current treatments for AL revolve around ablating the cancer plasma cell population using chemotherapy regimens. Unfortunately, this approach is limited to the ∼70% of patients who do not exhibit significant organ proteotoxicity and can tolerate chemotherapy. Thus, identifying new therapeutic strategies to alleviate LC organ proteotoxicity should allow AL patients with significant cardiac and/or renal involvement to subsequently tolerate established chemotherapy treatments. Using a small-molecule screening approach, the unfolded protein response (UPR) was identified as a cellular signaling pathway whose activation selectively attenuates secretion of amyloidogenic LC, while not affecting secretion of a nonamyloidogenic LC. Activation of the UPR-associated transcription factors XBP1s and/or ATF6 in the absence of stress recapitulates the selective decrease in amyloidogenic LC secretion by remodeling the endoplasmic reticulum proteostasis network. Stress-independent activation of XBP1s, or especially ATF6, also attenuates extracellular aggregation of amyloidogenic LC into soluble aggregates. Collectively, our results show that stress-independent activation of these adaptive UPR transcription factors offers a therapeutic strategy to reduce proteotoxicity associated with LC aggregation

Predictors for failure of supraglottic superimposed high-frequency jet ventilation during endoscopic upper airway surgery in pediatric patients

Airway surgery in pediatric patients is challenging with regard to balancing surgical exposure with ventilation requirements, as during the procedure the airway must be shared between laryngologist and anesthetist. For endoscopic laryngeal surgery, different methods of ventilation are used, among others jet ventilation via a specifically adapted suspension laryngoscope using a dual jet stream(Supraglottic Superimposed High Frequency Jet ventilation, SSHFJV) (1).High BMI and a history of pulmonary pathology proved to be factors contributing to failing of SSHFJV in adult patients (2). However, factors influencing the failure of SSHFJV in pediatric patients have never been described yet

Accelerated Particle Swarm Optimization and Support Vector Machine for Business Optimization and Applications

Business optimization is becoming increasingly important because all business activities aim to maximize the profit and performance of products and services, under limited resources and appropriate constraints. Recent developments in support vector machine and metaheuristics show many advantages of these techniques. In particular, particle swarm optimization is now widely used in solving tough optimization problems. In this paper, we use a combination of a recently developed Accelerated PSO and a nonlinear support vector machine to form a framework for solving business optimization problems. We first apply the proposed APSO-SVM to production optimization, and then use it for income prediction and project scheduling. We also carry out some parametric studies and discuss the advantages of the proposed metaheuristic SVM.Comment: 12 page

Cartoon Computation: Quantum-like computing without quantum mechanics

We present a computational framework based on geometric structures. No quantum mechanics is involved, and yet the algorithms perform tasks analogous to quantum computation. Tensor products and entangled states are not needed -- they are replaced by sets of basic shapes. To test the formalism we solve in geometric terms the Deutsch-Jozsa problem, historically the first example that demonstrated the potential power of quantum computation. Each step of the algorithm has a clear geometric interpetation and allows for a cartoon representation.Comment: version accepted in J. Phys.A (Letter to the Editor

Universal neural field computation

Turing machines and G\"odel numbers are important pillars of the theory of computation. Thus, any computational architecture needs to show how it could relate to Turing machines and how stable implementations of Turing computation are possible. In this chapter, we implement universal Turing computation in a neural field environment. To this end, we employ the canonical symbologram representation of a Turing machine obtained from a G\"odel encoding of its symbolic repertoire and generalized shifts. The resulting nonlinear dynamical automaton (NDA) is a piecewise affine-linear map acting on the unit square that is partitioned into rectangular domains. Instead of looking at point dynamics in phase space, we then consider functional dynamics of probability distributions functions (p.d.f.s) over phase space. This is generally described by a Frobenius-Perron integral transformation that can be regarded as a neural field equation over the unit square as feature space of a dynamic field theory (DFT). Solving the Frobenius-Perron equation yields that uniform p.d.f.s with rectangular support are mapped onto uniform p.d.f.s with rectangular support, again. We call the resulting representation \emph{dynamic field automaton}.Comment: 21 pages; 6 figures. arXiv admin note: text overlap with arXiv:1204.546

Pharmacologic IRE1/XBP1s Activation Confers Targeted ER Proteostasis Reprogramming

Activation of the IRE1/XBP1s signaling arm of the unfolded protein response (UPR) is a promising strategy to correct defects in endoplasmic reticulum (ER) proteostasis implicated in diverse diseases. However, no pharmacologic activators of this pathway identified to date are suitable for ER proteostasis remodeling through selective activation of IRE1/XBP1s signaling. Here, we use high-throughput screening to identify non-toxic compounds that induce ER proteostasis remodeling through IRE1/XBP1s activation. We employ transcriptional profiling to stringently confirm that our prioritized compounds selectively activate IRE1/XBP1s signaling without activating other cellular stress-responsive signaling pathways. Furthermore, we demonstrate that our compounds improve ER proteostasis of destabilized variants of amyloid precursor protein (APP) through an IRE1-dependent mechanism and reduce APP-associated mitochondrial toxicity in cellular models. These results establish highly selective IRE1/XBP1s activating compounds that can be widely employed to define the functional importance of IRE1/XBP1s activity for ER proteostasis regulation in the context of health and disease. [Figure not available: see fulltext.]