Differential detection of impact site versus rotational site injury by magnetic resonance imaging and microglial morphology in an unrestrained mild closed head injury model.

Seventy-five percent of all traumatic brain injuries are mild and do not cause readily visible abnormalities on routine medical imaging making it difficult to predict which individuals will develop unwanted clinical sequelae. Microglia are brain-resident macrophages and early responders to brain insults. Their activation is associated with changes in morphology or expression of phenotypic markers including P2Y12 and major histocompatibility complex class II. Using a murine model of unrestrained mild closed head injury (mCHI), we used microglia as reporters of acute brain injury at sites of impact versus sites experiencing rotational stress 24 h post-mCHI. Consistent with mild injury, a modest 20% reduction in P2Y12 expression was detected by quantitative real-time PCR (qPCR) analysis but only in the impacted region of the cortex. Furthermore, neither an influx of blood-derived immune cells nor changes in microglial expression of CD45, TREM1, TREM2, major histocompatibility complex class II or CD40 were detected. Using magnetic resonance imaging (MRI), small reductions in T2 weighted values were observed but only near the area of impact and without overt tissue damage (blood deposition, edema). Microglial morphology was quantified without cryosectioning artifacts using ScaleA(2) clarified brains from CX3CR1-green fluorescence protein (GFP) mice. The cortex rostral to the mCHI impact site receives greater rotational stress but neither MRI nor molecular markers of microglial activation showed significant changes from shams in this region. However, microglia in this rostral region did display signs of morphologic activation equivalent to that observed in severe CHI. Thus, mCHI-triggered rotational stress is sufficient to cause injuries undetectable by routine MRI that could result in altered microglial surveillance of brain homeostasis. Acute changes in microglial morphology reveal brain responses to unrestrained mild traumatic brain injury In areas subjected to rotational stress distant from impact site In the absence of detectable changes in standard molecular indicators of brain damage, inflammation or microglial activation. That might result in decreased surveillance of brain function and increased susceptibility to subsequent brain insults

Modeling Neural Immune Signaling of Episodic and Chronic Migraine Using Spreading Depression In Vitro

Migraine and its transformation to chronic migraine are healthcare burdens in need of improved treatment options. We seek to define how neural immune signaling modulates the susceptibility to migraine, modeled in vitro using spreading depression (SD), as a means to develop novel therapeutic targets for episodic and chronic migraine. SD is the likely cause of migraine aura and migraine pain. It is a paroxysmal loss of neuronal function triggered by initially increased neuronal activity, which slowly propagates within susceptible brain regions. Normal brain function is exquisitely sensitive to, and relies on, coincident low-level immune signaling. Thus, neural immune signaling likely affects electrical activity of SD, and therefore migraine. Pain perception studies of SD in whole animals are fraught with difficulties, but whole animals are well suited to examine systems biology aspects of migraine since SD activates trigeminal nociceptive pathways. However, whole animal studies alone cannot be used to decipher the cellular and neural circuit mechanisms of SD. Instead, in vitro preparations where environmental conditions can be controlled are necessary. Here, it is important to recognize limitations of acute slices and distinct advantages of hippocampal slice cultures. Acute brain slices cannot reveal subtle changes in immune signaling since preparing the slices alone triggers: pro-inflammatory changes that last days, epileptiform behavior due to high levels of oxygen tension needed to vitalize the slices, and irreversible cell injury at anoxic slice centers

L-Drawings of Directed Graphs

We introduce L-drawings, a novel paradigm for representing directed graphs aiming at combining the readability features of orthogonal drawings with the expressive power of matrix representations. In an L-drawing, vertices have exclusive $x$- and $y$-coordinates and edges consist of two segments, one exiting the source vertically and one entering the destination horizontally. We study the problem of computing L-drawings using minimum ink. We prove its NP-completeness and provide a heuristics based on a polynomial-time algorithm that adds a vertex to a drawing using the minimum additional ink. We performed an experimental analysis of the heuristics which confirms its effectiveness.Comment: 11 pages, 7 figure

Morphological Criteria for Diagnosis of Pulmonary Lesions of Lungs in Tumors Based on Resection Material

Morphological criteria of diagnosis of dust lesions of lungs in tumors on resectionmaterial are considered in the article. It is shown that the complex application of various research methods allows the identification of dust particles in the lung and lymph node tissues, and contributes to the improvement of the diagnosis of dust lesions of the respiratory system. Morphological characteristics of bauxite pneumoconiosis in primary lung cancer on resection material are presented

Performance robustness analysis in machine-assisted design of photonic devices

Machine-assisted design of integrated photonic devices (e.g. through optimization and inverse design methods) is opening the possibility of exploring very large design spaces, novel functionalities and non-intuitive geometries. These methods are generally used to optimize performance figures-of-merit. On the other hand, the effect of manufacturing variability remains a fundamental challenge since small fabrication errors can have a significant impact on light propagation, especially in high-index-contrast platforms. Brute-force analysis of these variabilities during the main optimization process can become prohibitive, since a large number of simulations would be required. To this purpose, efficient stochastic techniques integrated in the design cycle allow to quickly assess the performance robustness and the expected fabrication yield of each tentative device generated by the optimization. In this invited talk we present an overview of the recent advances in the implementation of stochastic techniques in photonics, focusing in particular on stochastic spectral methods that have been regarded as a promising alternative to the classical Monte Carlo method. Polynomial chaos expansion techniques generate so called surrogate models by means of an orthogonal set of polynomials to efficiently represent the dependence of a function to statistical variabilities. They achieve a considerable reduction of the simulation time compared to Monte Carlo, at least for mid-scale problems, making feasible the incorporation of tolerance analysis and yield optimization within the photonic design flow

Morphological diagnosis of dust lung damages associated with tumors

The publication is aimed at the morphological diagnosis optimization of dust lung damages associated with tumors. It describes characteristics of morphological changes of the lungs with the main types of professional dust pathology: silicosis, antracosis, antracomosis and electric welder pneumoconiosis. There are given histological criteria of lung damage in dust pathology and differential diagnosis. The final conclusion on professional dust pathology in operated patients has to be made by a pathologist with all methods of examination including morphological data.Цель статьи - совершенствование морфологической диагностики пылевых профессиональных поражений легких, ассоциированных с опухолями. Дана патоморфологическая картина при основных видах профессиональной пылевой патологии - силикозе, антракозе, антракокониозе, асбестозе, пневмокониозе электросварщика и непрофессиональных пылевых поражениях легких. Определена роль морфологического заключения для диагностики профессиональной патологии

Random Field Models for Relaxor Ferroelectric Behavior

Heat bath Monte Carlo simulations have been used to study a four-state clock model with a type of random field on simple cubic lattices. The model has the standard nonrandom two-spin exchange term with coupling energy $J$ and a random field which consists of adding an energy $D$ to one of the four spin states, chosen randomly at each site. This Ashkin-Teller-like model does not separate; the two random-field Ising model components are coupled. When $D / J = 3$, the ground states of the model remain fully aligned. When $D / J \ge 4$, a different type of ground state is found, in which the occupation of two of the four spin states is close to 50%, and the other two are nearly absent. This means that one of the Ising components is almost completely ordered, while the other one has only short-range correlations. A large peak in the structure factor $S (k)$ appears at small $k$ for temperatures well above the transition to long-range order, and the appearance of this peak is associated with slow, "glassy" dynamics. The phase transition into the state where one Ising component is long-range ordered appears to be first order, but the latent heat is very small.Comment: 7 pages + 12 eps figures, to appear in Phys Rev

Atomistic origins of high-performance in hybrid halide perovskite solar cells

The performance of organometallic perovskite solar cells has rapidly surpassed that of both conventional dye-sensitised and organic photovoltaics. High power conversion efficiency can be realised in both mesoporous and thin-film device architectures. We address the origin of this success in the context of the materials chemistry and physics of the bulk perovskite as described by electronic structure calculations. In addition to the basic optoelectronic properties essential for an efficient photovoltaic device (spectrally suitable band gap, high optical absorption, low carrier effective masses), the materials are structurally and compositionally flexible. As we show, hybrid perovskites exhibit spontaneous electric polarisation; we also suggest ways in which this can be tuned through judicious choice of the organic cation. The presence of ferroelectric domains will result in internal junctions that may aid separation of photoexcited electron and hole pairs, and reduction of recombination through segregation of charge carriers. The combination of high dielectric constant and low effective mass promotes both Wannier-Mott exciton separation and effective ionisation of donor and acceptor defects. The photoferroic effect could be exploited in nanostructured films to generate a higher open circuit voltage and may contribute to the current-voltage hysteresis observed in perovskite solar cells.Comment: 6 pages, 5 figure