Preferential utilization of ketone bodies for the synthesis of myelin cholesterol in vivo

1. The distribution of radioactivity among lipid classes of myelin and other subcellular brain fractions of young rats (18-21 days) was determined after in vivo injection of (3-(14)C-labelled ketone bodies, [U-(14)C] glucose or [2-(14)C] glucose. 2. The incorporation ratios (sterol/fatty acids) were 0.67, 1.48, 0.25, 0.62 and 0.54 for whole brain, myelin, mitochondria, microsomes and synaptosomes, respectively, with (3-(14)C)-labelled ketone bodies as substrate and 0.37, 0.89, 0.19, 0.34 and 0.29 with [U-(14)C] glucose as substrate. These data show that, both in whole brain and in subcellular brain fractions, acetyl groups derived from ketone bodies are used for sterol synthesis to a large extent than acetyl groups originating from glucose. 3. The specific radioactivity of cholesterol is much higher in myelin than in whole brain or in the other brain fractions, particularly after administration of labelled ketone bodies as substrate. 4. The incorporation patterns of acetoacetate and D-3-hydroxybutyrate were very similar, indicating that both ketone bodies contribute acetyl groups for lipid synthesis via the same metabolic route. 5. Our data suggest that a direct metabolic path from ketone bodies towards cholesterol exists - possibly via acetoacetyl-CoA formation in the cytosol of brain cells - and that this process is most active in oligodendrocytes.     

An improved snare system for the nonsurgical retrieval of intravascular foreign bodies

We have modified a snare technique originally described for transcolonoscopic removal of colonic polyps for the retrieval of intravascular foreign bodies. The key difference from other snare techniques is the employment of a wire snare with a crimp in its midportion that enables the formation of a loop in a plane perpendicular to the axial direction of the guiding catheter. With this technique we have quickly removed a variety of objects from the right heart and pulmonary arteries in four patients.     

Morphologic and functional changes in the unilateral 6-hydroxydopamine lesion rat model for Parkinson’s disease discerned with μSPECT and quantitative MRI

Object

In the present study, we aimed to evaluate the impact of neurodegeneration of the nigrostriatal tract in a rodent model of Parkinson’s disease on the different MR contrasts (T₂, T₁, CBF and CBV) measured in the striatum.

Material and methods

Animals were injected with 6-hydroxydopamine (6OHDA) in the substantia nigra resulting in massive loss of nigrostriatal neurons and hence dopamine depletion in the ipsilateral striatum. Using 7T MRI imaging, we have quantified T₂, T₁, CBF and CBV in the striata of 6OHDA and control rats. To validate the lesion size, behavioral testing, dopamine transporter μSPECT and tyrosine hydroxylase staining were performed.

Results

No significant differences were demonstrated in the absolute MRI values between 6OHDA animals and controls; however, 6OHDA animals showed significant striatal asymmetry for all MRI parameters in contrast to controls.

Conclusions

These PD-related asymmetry ratios might be the result of counteracting changes in both intact and affected striatum and allowed us to diagnose PD lesions. As lateralization is known to occur also in PD patients and might be expected in transgenic PD models as well, we propose that MR-derived asymmetry ratios in the striatum might be a useful tool for in vivo phenotyping of animal models of PD.     

Increasing Angiogenesis Factors in Hypoxic Diabetic Wound Conditions by siRNA Delivery: Additive Effect of LbL-Gold Nanocarriers and Desloratadine-Induced Lysosomal Escape

Impaired wound healing in people with diabetes has multifactorial causes, with insufficient neovascularization being one of the most important. Hypoxia-inducible factor-1 (HIF-1) plays a central role in the hypoxia-induced response by activating angiogenesis factors. As its activity is under precise regulatory control of prolyl-hydroxylase domain 2 (PHD-2), downregulation of PHD-2 by small interfering RNA (siRNA) could stabilize HIF-1α and, therefore, upregulate the expression of pro-angiogenic factors as well. Intracellular delivery of siRNA can be achieved with nanocarriers that must fulfill several requirements, including high stability, low toxicity, and high transfection efficiency. Here, we designed and compared the performance of layer-by-layer self-assembled siRNA-loaded gold nanoparticles with two different outer layers—Chitosan (AuNP@CS) and Poly L-arginine (AuNP@PLA). Although both formulations have exactly the same core, we find that a PLA outer layer improves the endosomal escape of siRNA, and therefore, transfection efficiency, after endocytic uptake in NIH-3T3 cells. Furthermore, we found that endosomal escape of AuNP@PLA could be improved further when cells were additionally treated with desloratadine, thus outperforming commercial reagents such as Lipofectamine^® and jetPRIME^®. AuNP@PLA in combination with desloratadine was proven to induce PHD-2 silencing in fibroblasts, allowing upregulation of pro-angiogenic pathways. This finding in an in vitro context constitutes a first step towards improving diabetic wound healing with siRNA therapy.     

Robust control charts for time series data

This article presents a control chart for time series data, based on the one-step-ahead forecast errors of the Holt–Winters forecasting method. We use robust techniques to prevent that outliers affect the estimation of the control limits of the chart. Moreover, robustness is important to maintain the reliability of the control chart after the occurrence of alarm observations. The properties of the new control chart are examined in a simulation study and on a real data example.     

Learning about the opponent in automated bilateral negotiation: a comprehensive survey of opponent modeling techniques

A negotiation between agents is typically an incomplete information game, where the agents initially do not know their opponent’s preferences or strategy. This poses a challenge, as efficient and effective negotiation requires the bidding agent to take the other’s wishes and future behavior into account when deciding on a proposal. Therefore, in order to reach better and earlier agreements, an agent can apply learning techniques to construct a model of the opponent. There is a mature body of research in negotiation that focuses on modeling the opponent, but there exists no recent survey of commonly used opponent modeling techniques. This work aims to advance and integrate knowledge of the field by providing a comprehensive survey of currently existing opponent models in a bilateral negotiation setting. We discuss all possible ways opponent modeling has been used to benefit agents so far, and we introduce a taxonomy of currently existing opponent models based on their underlying learning techniques. We also present techniques to measure the success of opponent models and provide guidelines for deciding on the appropriate performance measures for every opponent model type in our taxonomy.     

Handling Transitive Relations in First-Order Automated Reasoning

We present a number of alternative ways of handling transitive binary relations that commonly occur in first-order problems, in particular equivalence relations, total orders, and transitive relations in general. We show how such relations can be discovered syntactically in an input theory, and how they can be expressed in alternative ways. We experimentally evaluate different such ways on problems from the TPTP, using resolution-based reasoning tools as well as instance-based tools. Our conclusions are that (1) it is beneficial to consider different treatments of binary relations as a user, and that (2) reasoning tools could benefit from using a preprocessor or even built-in support for certain types of binary relations.

     

Efficient task scheduling for runtime reconfigurable systems

Recent research indicates the promising performance of employing reconfigurable systems to accelerate multimedia and communication applications. Nonetheless, they are yet to be widely adopted. One reason is the lack of efficient operating system support for these platforms. In this paper, we address the problem of runtime task scheduling as a main part of the operating systems. To do so, a new task replacement parameter, called Time-Improvement, is proposed for compiler assisted scheduling algorithms. In contrast with most related approach, we validate our approach using real application workload obtained from an application for multimedia test remotely taken by students. The proposed online task scheduling algorithm outperforms previous algorithms and accelerates task execution from 4% up to 20%.