Scalable parallel simulation of small-scale structures in cold dark matter

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Physics, 2005.Includes bibliographical references (p. 179-181).We present a parallel implementation of the particle-particle/particle-mesh (P³M) algorithm for distributed memory clusters. The llp3m-hc code uses a hybrid method for both computation and domain decomposition. Long-range forces are computed using a Fourier transform gravity solver on a regular mesh; the mesh is distributed across parallel processes using a static one-dimensional slab domain decomposition. Short-range forces are computed by direct summation of close pairs; particles are distributed using a dynamic domain decomposition based on a space-filling Hilbert curve. A nearly-optimal method was devised to dynamically repartition the particle distribution so as to maintain load balance even for extremely inhomogeneous mass distributions. Tests using 800³ simulations on a 40-processor Beowulf cluster showed good load balance and scalability up to 80 processes. We discuss the limits on scalability imposed by communication and extreme clustering and suggest how they may be removed by extending our algorithm to include a new adaptive P³M technique, which we then introduce and present as a new llap3m-hc code. We optimize free parameters of adaptive P³M to minimize force errors and the timing required to compute short range forces. We apply our codes to simulate small scale structure of the universe at redshift z > 50. We observe and analyze the formation of caustics in the structure and compare it with the predictions of semi-analytic models of structure formation. The current limits on neutralino detection experiments assume a Maxwell-Boltzmann velocity distribution and smooth spatial distribution of dark matter.(cont.) It is shown in this thesis that inhomogeneous distribution of dark matter on small scales significantly changes the predicted event rates in direct detection dark matter experiments. The effect of spatial inhomogeneity weakens the upper limits on neutralino cross section produced in the Cryogenic Dark Matter Search Experiment.by Alexander V. Shirokov.Ph.D

The imprints of primordial non-gaussianities on large-scale structure: scale dependent bias and abundance of virialized objects

We study the effect of primordial nongaussianity on large-scale structure, focusing upon the most massive virialized objects. Using analytic arguments and N-body simulations, we calculate the mass function and clustering of dark matter halos across a range of redshifts and levels of nongaussianity. We propose a simple fitting function for the mass function valid across the entire range of our simulations. We find pronounced effects of nongaussianity on the clustering of dark matter halos, leading to strongly scale-dependent bias. This suggests that the large-scale clustering of rare objects may provide a sensitive probe of primordial nongaussianity. We very roughly estimate that upcoming surveys can constrain nongaussianity at the level |fNL| <~ 10, competitive with forecasted constraints from the microwave background.Comment: 16 pages, color figures, revtex4. v2: added references and an equation. submitted to PRD. v3: simplified derivation, additional reference

Анатомия хайпа вокруг No Man’s Sky: интернет-платформы и барьеры демонстрации видеоигр

Статья посвящена истории, приключившейся с одной из самых ожидаемых видеоигр последних лет—No Man’s Sky. Данная игра разрабатывалась около пяти лет и почти все это время была окружена хайпом и медийным шумом, которые привели к колоссальным ожиданиям от игры. В глазах аудитории она должна была стать революцией в игровой индустрии. Однако после выхода игра получила низкие оценки игровой прессы, и крайне отрицательные отзывы игроков. В адрес разработчиков посыпались всевозможные обвинения, предполагающие, что в самой игре отсутствовали многие возможности, показанные в трейлерах. Опираясь на теоретические ресурсы platform studies и понятие демонстрации, авторы пытаются ответить вопрос о том, почему игра провалилась. На основе проведенного исследования специфики трейлеров и комментариев пользователей платформы YouTube, авторы пришли к выводу, что провал игры, с одной стороны, результат не прямой лжи со стороны разработчиков, а недосказанности в отношении игры, не информативности её демонстраций, вследствие чего они были открыты для интерпретаций и работы воображения. Эта открытость также связана с барьерами форм демонстраций видеоигр, которые не позволяют передать непосредственный опыт игрового процесса. С другой стороны, к неудаче, постигшей No Man’s Sky, привела специфика функционирования YouTube как платформы, позволяющей аудитории участвовать в создании того, что можно было бы назвать «медийной версией» реальности No Man’s Sky. Эта версия оказалась куда более масштабной и грандиозной, чем сама No Man’s Sky. Проблема в том, что разработчики не ограничивали разрастание этой «медийной версии», что в итоге и привело к провалу столь ожидаемой игры. Таким образом, можно говорить о множественном характере современных культурных объектов, в производстве которого участвуют и сами пользователи

Application of optical coherence tomography for in vivo monitoring of the meningeal lymphatic vessels during opening of blood–brain barrier: mechanisms of brain clearing

The meningeal lymphatic vessels were discovered 2 years ago as the drainage system involved in the mechanisms underlying the clearance of waste products from the brain. The blood–brain barrier (BBB) is a gatekeeper that strongly controls the movement of different molecules from the blood into the brain. We know the scenarios during the opening of the BBB, but there is extremely limited information on how the brain clears the substances that cross the BBB. Here, using the model of sound-induced opening of the BBB, we clearly show how the brain clears dextran after it crosses the BBB via the meningeal lymphatic vessels. We first demonstrate successful application of optical coherence tomography (OCT) for imaging of the lymphatic vessels in the meninges after opening of the BBB, which might be a new useful strategy for noninvasive analysis of lymphatic drainage in daily clinical practice. Also, we give information about the depth and size of the meningeal lymphatic vessels in mice. These new fundamental data with the applied focus on the OCT shed light on the mechanisms of brain clearance and the role of lymphatic drainage in these processes that could serve as an informative platform for a development of therapy and diagnostics of diseases associated with injuries of the BBB such as stroke, brain trauma, glioma, depression, or Alzheimer disease

Music improves the therapeutic effects of bevacizumab in rats with glioblastoma: Modulation of drug distribution to the brain

Background: The development of new methods for modulation of drug distribution across to the brain is a crucial step in the effective therapies for glioblastoma (GBM). In our previous work, we discovered the phenomenon of music-induced opening of the blood-brain barrier (OBBB) in healthy rodents. In this pilot study on rats, we clearly demonstrate that music-induced BBB opening improves the therapeutic effects of bevacizumab (BZM) in rats with GBM via increasing BZM distribution to the brain along the cerebral vessels. Methods: The experiments were performed on Wistar male rats (200-250 g, n=161) using transfected C6-TagRFP cell line and the loud rock music for OBBB. The OBBB was assessed by spectrofluorometric assay of Evans Blue (EB) extravasation and confocal imaging of fluorescent BZM (fBZM) delivery into the brain. Additionally, distribution of fBZM and Omniscan in the brain was studied using fluorescent and magnetic resonance imaging (MRI), respectively. To analyze the therapeutic effects of BZM on the GBM growth in rats without and with OBBB, the GBM volume (MRI scans), as well as immunohistochemistry assay of proliferation (Ki67 marker) and apoptosis (Bax marker) in the GBM cells were studied. The Mann-Whitney-Wilcoxon test was used for all analysis, the significance level was p < 0.05, n=7 in each group. Results: Our finding clearly demonstrates that music-induced OBBB increases the delivery of EB into the brain tissues and the extravasation of BZM into the brain around the cerebral vessels of rats with GBM. Music significantly increases distribution of tracers (fBZM and Omniscan) in the rat brain through the pathways of brain drainage system (perivascular and lymphatic), which are an important route of drug delivery into the brain. The music-induced OBBB improves the suppressive effects of BZM on the GBM volume and the cellular mechanisms of tumor progression that was accompanied by higher survival among rats in the GBM+BZM+Music group vs. other groups. Conclusion: We hypothesized that music improves the therapeutic effects of BZM via OBBB in the normal cerebral vessels and lymphatic drainage of the brain tissues. This contributes better distribution of BZM in the brain fluids and among the normal cerebral vessels, which are used by GBM for invasion and co-opt existing vessels as a satellite tumor form. These results open the new perspectives for an improvement of therapeutic effects of BZM via the music-induced OBBB for BZM in the normal cerebral vessels, which are used by GBM for migration and progression

Photodynamic opening of the blood-brain barrier using different photosensitizers in mice

In a series of previous studies, we demonstrated that the photodynamic therapy (PDT), as a widely used tool for treatment of glioblastoma multiforme (GBM), also site-specifically opens the blood-brain barrier (BBB) in PDT-dose and age-related manner via reversible disorganization of the tight junction machinery. To develop the effective protocol of PDT-opening of the BBB, here we answer the question of what kind of photosensitizer (PS) is the most effective for the BBB opening. We studied the PDT-opening of the BBB in healthy mice using commercial photosensitizers (PSs) such as 5-aminolevulenic acid (5-ALA), aluminum phthalocyanine disulfonate (AlPcS), zinc phthalocyanine (ZnPc) and new synthetized PSs such as galactose functionalized ZnPc (GalZnPc). The spectrofluorimetric assay of Evans Blue albumin complex (EBAC) leakage and 3-D confocal imaging of FITC-dextran 70 kDa (FITCD) extravasation clearly shows a revisable and dose depended PDT-opening of the BBB toEBACand FITCD associated with a decrease in presence of tight junction (TJ) in the vascular endothelium. The PDT effects on the BBB permeability, TJ expression and the fluorescent signal from the brain tissues are more pronounced in PDT-GalZnPc vs. PDT-5-ALA/AlPcS/ZnPc. These pre-clinical data are the first important informative platform for an optimization of the PDT protocol in the light of new knowledge about PDT-opening of the BBB for drug brain delivery and for the therapy of brain diseases. © 2019 by the authors

Photobiomodulation of lymphatic drainage and clearance: perspective strategy for augmentation of meningeal lymphatic functions

There is a hypothesis that augmentation of the drainage and clearing function of the meningeal lymphatic vessels (MLVs) might be a promising therapeutic target for preventing neurological diseases. Here we investigate mechanisms of photobiomodulation (PBM, 1267 nm) of lymphatic drainage and clearance. Our results obtained at optical coherence tomography (OCT) give strong evidence that low PBM doses (5 and 10 J/cm2) stimulate drainage function of the lymphatic vessels via vasodilation (OCT data on the mesenteric lymphatics) and stimulation of lymphatic clearance (OCT data on clearance of gold nanorods from the brain) that was supported by confocal imaging of clearance of FITC-dextran from the cortex via MLVs. We assume that PBM-mediated relaxation of the lymphatic vessels can be possible mechanisms underlying increasing the permeability of the lymphatic endothelium that allows molecules transported by the lymphatic vessels and explain PBM stimulation of lymphatic drainage and clearance. These findings open new strategies for the stimulation of MLVs functions and non-pharmacological therapy of brain diseases