Improved Central Limit Theorem and bootstrap approximations in high dimensions

This paper deals with the Gaussian and bootstrap approximations to the distribution of the max statistic in high dimensions. This statistic takes the form of the maximum over components of the sum of independent random vectors and its distribution plays a key role in many high-dimensional econometric problems. Using a novel iterative randomized Lindeberg method, the paper derives new bounds for the distributional approximation errors. These new bounds substantially improve upon existing ones and simultaneously allow for a larger class of bootstrap methods.Comment: 53 page

Intravascular heavy chain-modification of hyaluronan during endotoxic shock

During inflammation, the covalent linking of the ubiquitous extracellular polysaccharide hyaluronan (HA) with the heavy chains (HC) of the serum protein inter alpha inhibitor (IαI) is exclusively mediated by the enzyme tumor necrosis factor α (TNFα)-stimulated-gene-6 (TSG-6). While significant advances have been made regarding how HC-modified HA (HC-HA) is an important regulator of inflammation, it remains unclear why HC-HA plays a critical role in promoting survival in intraperitoneal lipopolysaccharide (LPS)-induced endotoxemia while exerting only a modest role in the outcomes following intratracheal exposure to LPS. To address this gap, the two models of intraperitoneal LPS-induced endotoxic shock and intratracheal LPS-induced acute lung injury were directly compared in TSG-6 knockout mice and littermate controls. HC-HA formation, endogenous TSG-6 activity, and inflammatory markers were assessed in plasma and lung tissue. TSG-6 knockout mice exhibited accelerated mortality during endotoxic shock. While both intraperitoneal and intratracheal LPS induced HC-HA formation in lung parenchyma, only systemically-induced endotoxemia increased plasma TSG-6 levels and intravascular HC-HA formation. Cultured human lung microvascular endothelial cells secreted TSG-6 in response to both TNFα and IL1β stimulation, indicating that, in addition to inflammatory cells, the endothelium may secrete TSG-6 into circulation during systemic inflammation. These data show for the first time that LPS-induced systemic inflammation is uniquely characterized by significant vascular induction of TSG-6 and HC-HA, which may contribute to improved outcomes of endotoxemia

Chronology Protection and Non-Naked Singularity

We test the chronology protection conjecture in classical general relativity by investigating finitely vicious space-times. First we present singularity theorems in finitely vicious space-times by imposing some restrictions on the chronology violating sets. In the theorems we can refer to the location of an occurring singularity and do not assume any asymptotic conditions such as the existence of null infinities. Further introducing the concept of a non-naked singularity, we show that a restricted class of chronology violations cannot arise if all occurring singularities are the non-naked singularities. Our results suggest that the causal feature of the occurring singularities is the key to prevent the appearance of causality violation.Comment: 17 pages including 3 eps figures. Accepted for publication in Classical and Quantum Gravit

Upper bound for entropy in asymptotically de Sitter space-time

We investigate nature of asymptotically de Sitter space-times containing a black hole. We show that if the matter fields satisfy the dominant energy condition and the cosmic censorship holds in the considering space-time, the area of the cosmological event horizon for an observer approaching a future timelike infinity does not decrease, i.e. the second law is satisfied. We also show under the same conditions that the total area of the black hole and the cosmological event horizon, a quarter of which is the total Bekenstein-Hawking entropy, is less than $12\pi/\Lambda$, where $\Lambda$ is a cosmological constant. Physical implications are also discussed.Comment: 9 pages, REVTeX,2 figures; to be published in Phys.Rev.

The YUIMA project : a computational framework for simulation and inference of stochastic differential equations

The Yuima Project is an open source and collaborative e ort aimed at developing the R package named yuima for simulation and inference of stochastic di erential equations. In the yuima package, stochastic di erential equations can be of very abstract type, multidimensional, driven by Wiener process or fractional Brownian motion with general Hurst parameter, with or without jumps speci ed as L evy noise. The yuima package is intended to o er the basic infrastructure on which complex models and inference procedures can be built on. The computational framework implemented allow for the estimation of high frequency data and also o er the ability to perform Monte Carlo anal- ysis using cluster infrastructure whenever available in a transparent way to the user. Some real examples of model implementation and data estimation will be considere

Hochuekkito (TJ-41), a Kampo Formula, Ameliorates Cachexia Induced by Colon 26 Adenocarcinoma in Mice

Cachexia, a major cause of cancer-related death, is characterized by depletion of muscle and fat tissues, anorexia, asthenia, and hypoglycemia. Recent studies indicate that secretions of proinflammatory cytokines such as interleukin-6 (IL-6) play a crucial role in cachexia development, and that these cytokines are secreted from not only cancer cells but also host cells such as macrophages. In this study, we investigated the therapeutic effects of hochuekkito, a Kampo formula, on cachexia induced by colon 26 adenocarcinoma in mice. Hochuekkito treatment did not inhibit tumor growth, but significantly attenuated the reduction in carcass weight, food and water intake, weight of the gastrocnemius muscle and fat tissue around the testes, and decrease of serum triglyceride level compared with controls. Furthermore, hochuekkito treatment significantly reduced serum IL-6 level and IL-6 expression level in macrophages in tissues surrounding the tumor. In vitro studies showed that hochuekkito suppressed the production of IL-6 by THP-1 or RAW264.7 macrophage cells, although it did not affect IL-6 production by colon 26 carcinoma cells. These results suggest that hochuekkito inhibits the production of proinflammatory cytokines, particularly IL-6, by host cells such as macrophages. Therefore, hochuekkito may be a promising anticachectic agent for the treatment of patients with cancer

SAHG, a comprehensive database of predicted structures of all human proteins

Most proteins from higher organisms are known to be multi-domain proteins and contain substantial numbers of intrinsically disordered (ID) regions. To analyse such protein sequences, those from human for instance, we developed a special protein-structure-prediction pipeline and accumulated the products in the Structure Atlas of Human Genome (SAHG) database at http://bird.cbrc.jp/sahg. With the pipeline, human proteins were examined by local alignment methods (BLAST, PSI-BLAST and Smith–Waterman profile–profile alignment), global–local alignment methods (FORTE) and prediction tools for ID regions (POODLE-S) and homology modeling (MODELLER). Conformational changes of protein models upon ligand-binding were predicted by simultaneous modeling using templates of apo and holo forms. When there were no suitable templates for holo forms and the apo models were accurate, we prepared holo models using prediction methods for ligand-binding (eF-seek) and conformational change (the elastic network model and the linear response theory). Models are displayed as animated images. As of July 2010, SAHG contains 42 581 protein-domain models in approximately 24 900 unique human protein sequences from the RefSeq database. Annotation of models with functional information and links to other databases such as EzCatDB, InterPro or HPRD are also provided to facilitate understanding the protein structure-function relationships

Identification of NeuN immunopositive cells in the adult mouse subventricular zone

In the adult rodent subventricular zone (SVZ), there are neural stem cells (NSCs) and the specialized neurogenic niche is critical to maintain their stemness. To date, many cellular and noncellular factors that compose the neurogenic niche and markers to identify subpopulations of Type A cells have been confirmed. In particular, neurotransmitters regulate adult neurogenesis and mature neurons in the SVZ have been only partially analyzed. Moreover, Type A cells, descendants of NSCs, are highly heterogeneous and more molecular markers are still needed to identify them. In the present study, we systematically classified NeuN, commonly used as a marker of mature and immature post‐mitotic neurons, immunopositive (+) cells within the adult mouse SVZ. These SVZ‐NeuN+ cells (SVZ‐Ns) were mainly classified into two types. One was mature SVZ‐Ns (M‐SVZ‐Ns). Neurochemical properties of M‐SVZ‐Ns were similar to those of striatal neurons, but their birth date and morphology were different. M‐SVZ‐Ns were generated during embryonic and early postnatal stages with bipolar peaks and extended their processes along the wall of the lateral ventricle. The second type was small SVZ‐Ns (S‐SVZ‐Ns) with features of Type A cells. They expressed not only markers of Type A cells, but also proliferated and migrated from the SVZ to the olfactory bulb. Furthermore, S‐SVZ‐Ns could be classified into two types by their spatial locations and glutamic acid decarboxylase 67 expression. Our data indicate that M‐SVZ‐Ns are a new component of the neurogenic niche and S‐SVZ‐Ns are newly identified subpopulations of Type A cells

Sphingolipids in COPD

Sphingolipids are a distinct class of lipid molecules widely found in nature, principally as cell membrane constituents. After initial uncertainty about their function, sphingolipids have been increasingly recognised to be metabolically active entities involved in many biological processes, including the control of inflammation. Their role as mediators of inflammation may have significant implications for a range of lung diseases in which inflammation is a central element of pathogenesis. Chronic obstructive pulmonary disease (COPD), a highly prevalent and morbid condition predominantly affecting cigarette smokers, is a prime example of a respiratory illness with an inflammatory component. Understandably, sphingolipids have received growing attention for their increasingly demonstrated role in the pathophysiology of COPD. The present review aims to be among the first to focus exclusively on the connection between sphingolipids and lung inflammation in COPD, providing the reader with a clinically oriented synopsis of this intriguing association

Moderate Thermal Stress Causes Active and Immediate Expulsion of Photosynthetically Damaged Zooxanthellae (Symbiodinium) from Corals.

The foundation of coral reef biology is the symbiosis between corals and zooxanthellae (dinoflagellate genus Symbiodinium). Recently, coral bleaching, which often results in mass mortality of corals and the collapse of coral reef ecosystems, has become an important issue around the world as coral reefs decrease in number year after year. To understand the mechanisms underlying coral bleaching, we maintained two species of scleractinian corals (Acroporidae) in aquaria under non-thermal stress (27°C) and moderate thermal stress conditions (30°C), and we compared the numbers and conditions of the expelled Symbiodinium from these corals. Under non-thermal stress conditions corals actively expel a degraded form of Symbiodinium, which are thought to be digested by their host coral. This response was also observed at 30°C. However, while the expulsion rates of Symbiodinium cells remained constant, the proportion of degraded cells significantly increased at 30°C. This result indicates that corals more actively digest and expel damaged Symbiodinium under thermal stress conditions, likely as a mechanism for coping with environmental change. However, the increase in digested Symbiodinium expulsion under thermal stress may not fully keep up with accumulation of the damaged cells. There are more photosynthetically damaged Symbiodinium upon prolonged exposure to thermal stress, and corals release them without digestion to prevent their accumulation. This response may be an adaptive strategy to moderate stress to ensure survival, but the accumulation of damaged Symbiodinium, which causes subsequent coral deterioration, may occur when the response cannot cope with the magnitude or duration of environmental stress, and this might be a possible mechanism underlying coral bleaching during prolonged moderate thermal stress