Night Photostimulation of Clearance of Beta-Amyloid from Mouse Brain: New Strategies in Preventing Alzheimer’s Disease

The deposition of amyloid-β (Aβ) in the brain is a risk factor for Alzheimer’s disease (AD). Therefore, new strategies for the stimulation of Aβ clearance from the brain can be useful in preventing AD. Transcranial photostimulation (PS) is considered a promising method for AD therapy. In our previous studies, we clearly demonstrated the PS-mediated stimulation of lymphatic clearing functions, including Aβ removal from the brain. There is increasing evidence that sleep plays an important role in Aβ clearance. Here, we tested our hypothesis that PS at night can stimulate Aβ clearance from the brain more effectively than PS during the day. Our results on healthy mice show that Aβ clearance from the brain occurs faster at night than during wakefulness. The PS course at night improves memory and reduces Aβ accumulation in the brain of AD mice more effectively than the PS course during the day. Our results suggest that night PS is a more promising candidate as an effective method in preventing AD than daytime PS. These data are an important informative platform for the development of new noninvasive and nonpharmacological technologies for AD therapy as well as for preventing Aβ accumulation in the brain of people with disorder of Aβ metabolism, sleep deficit, elderly age, and jet lag.

Noninvasive technology of photostimulation of lymphatic clearance of red blood cells from the mouse brain after intraventricular hemorrhage.

Intraventricular hemorrhage (IVH) is the most fatal form of brain injury in adults and infants. However, therapy of IVH is very limited, and new strategies are needed to reduce hematoma expansion. For the first time, in our experiments on mice with IVH, we clearly demonstrate that transcranial low-level infra-red photostimulation (PS) accelerates the red blood cells (RBCs) evacuation from the ventricles that is associated with reducing the mortality in 1.57 times, improving emotional status and recovery of intracranial pressure. We revealed the mechanisms of PS-modulation of lymphatic contractility and tone of the lymphatic vessels underlying the lymphatic clearing functions. Our findings strongly suggest that PS-mediated stimulation of lymphatic clearance of RBCs can be a novel non-invasive, bedside, readily applicable, and commercially viable technology for the treatment of IVH.

A Model for Demand Planning in Supply Chains with Congestion Effects

This paper is concerned with demand planning for internal supply chains consisting of workstations, production facilities, warehouses, and transportation links. We address the issue of how to help a supplier firmly accept orders and subsequently plan to fulfill demand. We first formulate a linear aggregate planning model for demand management that incorporates elements of order promising, recipe run constraints, and capacity limitations. Using several scenarios, we discuss the use of the model in demand planning and capacity planning to help a supplier firmly respond to requests for quotations. We extend the model to incorporate congestion effects at assembly and blending nodes using clearing functions; the resulting model is nonlinear. We develop and test two algorithms to solve the nonlinear model: one based on inner approximation and the other on outer approximation.

Photostimulation of lymphatic clearance of red blood cells from the mouse brain after intraventricular hemorrhage

Intraventricular hemorrhage (IVH) is the most fatal form of brain injury, yet a therapy directed at ameliorating intraventricular clot is very limited. There is accumulating evidence that an augmentation of the meningeal lymphatic (MLVs) functions might be a promising therapeutic target for IVH. In particular, the photostimulation (PS) of MLVs could be promising for non-invasive therapy of IVH via PS of clearance of red blood cells (RBCs) from the brain via MLVs. Indeed, we uncover that PS has therapeutic effects on IVH in mice reducing the mortality, improving the emotional status, accelerating the RBCs evacuation from the ventricles and increasing the ICP recovery. Our findings strongly suggest that the PS-mediated stimulation of drainage and clearing functions of MLVs can be a novel bedside, readily applicable and commercially viable technologies for treatment of IVH. These pilot results open new horizons in a non-invasive therapy of IVH via PS stimulation of regenerative lymphatic mechanisms.

A Selective Fault Clearing Scheme for a Hybrid VSC-LCC Multi-Terminal HVdc System

A selective fault clearing scheme is proposed for a hybrid voltage source converter (VSC)-line commutated converter (LCC) multi-terminal high voltage direct current (HVdc) transmission structure in which two small capacity VSC stations tap into the main transmission line of a high capacity LCC-HVdc link. The use of dc circuit breakers (dc CBs) on the branches connecting to VSCs at the tapping points is explored to minimize the impact of tapping on the reliability of the main LCC link. This arrangement allows clearing of temporary faults on the main LCC line as usual by force retardation of the LCC rectifier. The faults on the branches connecting to VSC stations can be cleared by blocking insulated gate bipolar transistors (IGBTs) and opening ac circuit breakers (ac CB), without affecting the main line’s performance. A local voltage and current measurement based fault discrimination scheme is developed to identify the faulted sections and pole(s), and trigger appropriate fault recovery functions. This fault discrimination scheme is capable of detecting and discriminating short circuits and high resistances faults in any branch well before 2 ms. For the test grid considered, 6 kA, 2 ms dc CBs can easily facilitate the intended fault clearing functions and maintain the power transfer through healthy pole during single-pole faults.

The Settlement Infrastructure of Ukrainian Stock Market: State and Directions for Reform

The research defines the concepts of clearing and clearing activity. It explores the models of the clearing institutions’ organizational structure in EU countries. It also outlines the directions for the settlement and clearing infrastructure reform based on the diversification of the settlement and clearing functions. It should ensure the integrity of the stock market, the reduction of risks, the creation of an efficient and transparent system for the execution of transactions with securities; reduction of expenses of market participants; acceleration of payment terms for operations with securities and process of registration of property rights; differentiation of responsibility at different stages of performance of transactions. The author has defined the legal status of the Financial Settlements Center as a banking institution with a special legal personality of the conducting monetary settlements under transactions concerning securities and other financial instruments, made on the stock exchange and outside the stock exchange, if payments are made according to the principle of ‘supply against payment’. The study shows the need for the universal model of settlements to serve all the exchange markets. We offer to demonopolize the market of clearing services and to provide access for international clearing institutions. We also suggest transferring the settlement function to the Central Depositary and the clearing function – to clearing institutions.