Neurite imaging reveals microstructural variations in human cerebral cortical gray matter

We present distinct patterns of neurite distribution in the human cerebral cortex using diffusion magnetic resonance imaging (MRI). We analyzed both high-resolution structural (T1w and T2w images) and diffusion MRI data in 505 subjects from the Human Connectome Project. Neurite distributions were evaluated using the neurite orientation dispersion and density imaging (NODDI) model, optimized for gray matter, and mapped onto the cortical surface using a method weighted towards the cortical mid-thickness to reduce partial volume effects. The estimated neurite density was high in both somatosensory and motor areas, early visual and auditory areas, and middle temporal area (MT), showing a strikingly similar distribution to myelin maps estimated from the T1w/T2w ratio. The estimated neurite orientation dispersion was particularly high in early sensory areas, which are known for dense tangential fibers and are classified as granular cortex by classical anatomists. Spatial gradients of these cortical neurite properties revealed transitions that colocalize with some areal boundaries in a recent multi-modal parcellation of the human cerebral cortex, providing mutually supportive evidence. Our findings indicate that analyzing the cortical gray matter neurite morphology using diffusion MRI and NODDI provides valuable information regarding cortical microstructure that is related to but complementary to myeloarchitecture

String solitons in the M5-brane worldvolume with a Nambu-Poisson structure and Seiberg-Witten map

We analyze BPS equations for string-like configurations derived from the M5-brane worldvolume action with a Nambu-Poisson structure constructed in arXiv:0804.3629, arXiv:0805.2898. We solve the BPS equations up to the first order in the parameter $g$ which characterizes the strength of the Nambu-Poisson bracket. We compare our solutions to previously constructed BPS string solitons in the conventional description of M5-brane in a constant three-form background via Seiberg-Witten map, and find agreement.Comment: v2: minor corrections, the title slightly changed. 10 pages. v3: some clarifying comment

Branes from a non-Abelian (2,0) tensor multiplet with 3-algebra

In this paper, we study the equations of motion for non-Abelian N=(2,0) tensor multiplets in six dimensions, which were recently proposed by Lambert and Papageorgakis. Some equations are regarded as constraint equations. We employ a loop extension of the Lorentzian three-algebra (3-algebra) and examine the equations of motion around various solutions of the constraint equations. The resultant equations take forms that allow Lagrangian descriptions. We find various (5+d)-dimensional Lagrangians and investigate the relation between them from the viewpoint of M-theory duality.Comment: 44+1 pages, reference added, typos corrected, and several discussions added; v3, reference added, many typos corrected, the language improved; v4, some typos and references corrected, final version to appear in J. Phys.

An anisotropic hybrid non-perturbative formulation for 4D N = 2 supersymmetric Yang-Mills theories

We provide a simple non-perturbative formulation for non-commutative four-dimensional N = 2 supersymmetric Yang-Mills theories. The formulation is constructed by a combination of deconstruction (orbifold projection), momentum cut-off and matrix model techniques. We also propose a moduli fixing term that preserves lattice supersymmetry on the deconstruction formulation. Although the analogous formulation for four-dimensional N = 2 supersymmetric Yang-Mills theories is proposed also in Nucl.Phys.B857(2012), our action is simpler and better suited for computer simulations. Moreover, not only for the non-commutative theories, our formulation has a potential to be a non-perturbative tool also for the commutative four-dimensional N = 2 supersymmetric Yang-Mills theories.Comment: 32 pages, final version accepted in JHE

Phase I study of TP300 in patients with advanced solid tumors with pharmacokinetic, pharmacogenetic and pharmacodynamic analyses

Background: A Phase I dose escalation first in man study assessed maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and recommended Phase II dose of TP300, a water soluble prodrug of the Topo-1 inhibitor TP3076, and active metabolite, TP3011. <p/>Methods: Eligible patients with refractory advanced solid tumors, adequate performance status, haematologic, renal, and hepatic function. TP300 was given as a 1-hour i.v. infusion 3-weekly and pharmacokinetic (PK) profiles of TP300, TP3076 and TP3011 were analysed. Polymorphisms in CYP2D6, AOX1 and UGT1A1 were studied and DNA strand-breaks measured in peripheral blood mononuclear cells (PBMCs). <p/>Results: 32 patients received TP300 at 1, 2, 4, 6, 8, 10, 12 mg/m2. MTD was 10 mg/m2; DLTs at 12 (2/4 patients) and 10 mg/m2 (3/12) included thrombocytopenia and febrile neutropenia; diarrhea was uncommon. Six patients (five had received irinotecan), had stable disease for 1.5-5 months. TP3076 showed dose proportionality in AUC and Cmax from 1--10 mg/m2. Genetic polymorphisms had no apparent influence on exposure. DNA strand-breaks were detected after TP300 infusion. <p/>Conclusions: TP300 had predictable hematologic toxicity, and diarrhea was uncommon. AUC at MTD is substantially greater than for SN38. TP3076 and TP3011 are equi-potent with SN38, suggesting a PK advantage

A No-Go Theorem for M5-brane Theory

The BLG model for multiple M2-branes motivates an M5-brane theory with a novel gauge symmetry defined by the Nambu-Poisson structure. This Nambu-Poisson gauge symmetry for an M5-brane in large C-field background can be matched, on double dimension reduction, with the Poisson limit of the noncommutative gauge symmetry for a D4-brane in B-field background. Naively, one expects that there should exist a certain deformation of the Nambu-Poisson structure to match with the full noncommutative gauge symmetry including higher order terms. However, We prove the no-go theorem that there is no way to deform the Nambu-Poisson gauge symmetry, even without assuming the existence of a deformation of Nambu-Poisson bracket, to match with the noncommutative gauge symmetry in 4+1 dimensions to all order, regardless of how the double dimension reduction is implemented.Comment: v4: minor modifications

The Nature of Ultra-Luminous Compact X-Ray Sources in Nearby Spiral Galaxies

Studies were made of ASCA spectra of seven ultra-luminous compact X-ray sources (ULXs) in nearby spiral galaxies; M33 X-8 (Takano et al. 1994), M81 X-6 (Fabbiano 1988b; Kohmura et al. 1994; Uno 1997), IC 342 Source 1 (Okada et al. 1998), Dwingeloo 1 X-1 (Reynolds et al. 1997), NGC 1313 Source B (Fabbiano & Trinchieri 1987; Petre et al. 1994), and two sources in NGC 4565 (Mizuno et al. 1999). With the 0.5--10 keV luminosities in the range 10^{39-40} ergs/s, they are thought to represent a class of enigmatic X-ray sources often found in spiral galaxies. For some of them, the ASCA data are newly processed, or the published spectra are reanalyzed. For others, the published results are quoted. The ASCA spectra of all these seven sources have been described successfully with so called multi-color disk blackbody (MCD) emission arising from optically-thick standard accretion disks around black holes. Except the case of M33 X-8, the spectra do not exhibit hard tails. For the source luminosities not to exceed the Eddington limits, the black holes are inferred to have rather high masses, up to ~100 solar masses. However, the observed innermost disk temperatures of these objects, Tin = 1.1--1.8 keV, are too high to be compatible with the required high black-hole masses, as long as the standard accretion disks around Schwarzschild black holes are assumed. Similarly high disk temperatures are also observed from two Galactic transients with superluminal motions, GRO 1655-40 and GRS 1915+105. The issue of unusually high disk temperature may be explained by the black hole rotation, which makes the disk get closer to the black hole, and hence hotter.Comment: submitted to ApJ, December 199

More on the Nambu-Poisson M5-brane Theory: Scaling limit, background independence and an all order solution to the Seiberg-Witten map

We continue our investigation on the Nambu-Poisson description of M5-brane in a large constant C-field background (NP M5-brane theory) constructed in Refs.[1, 2]. In this paper, the low energy limit where the NP M5-brane theory is applicable is clarified. The background independence of the NP M5-brane theory is made manifest using the variables in the BLG model of multiple M2-branes. An all order solution to the Seiberg-Witten map is also constructed.Comment: expanded explanations, minor corrections and typos correcte

Discovery of Genes Activated by the Mitochondrial Unfolded Protein Response (mtUPR) and Cognate Promoter Elements

In an accompanying paper, we show that the mitochondrial Unfolded Protein Response or mtUPR is initiated by the activation of transcription of chop through an AP-1 element in the chop promoter. Further, we show that the c/ebpβ gene is similarly activated and CHOP and C/EBPβ subsequently hetero-dimerise to activate transcription of mtUPR responsive genes. Here, we report the discovery of six additional mtUPR responsive genes. We found that these genes encoding mitochondrial proteases YME1L1 and MPPβ, import component Tim17A and enzymes NDUFB2, endonuclease G and thioredoxin 2, all contain a CHOP element in their promoters. In contrast, genes encoding mitochondrial proteins Afg3L2, Paraplegin, Lon and SAM 50, which do not have a CHOP element, were not up-regulated. Conversely, genes with CHOP elements encoding cytosolic proteins were not induced by the accumulation of unfolded proteins in mitochondria. These results indicate that mtUPR responsive genes appear to share a requirement for a CHOP element, but that this is not sufficient for the regulation of the mtUPR. A more detailed analysis of promoters of mtUPR responsive genes revealed at least two additional highly conserved, putative regulatory sites either side of the CHOP element, one a motif of 12 bp which lies 14 bp upstream of the CHOP site and another 9 bp element, 2 bp downstream of the CHOP site. Both of these additional elements are conserved in the promoters of 9 of the ten mtUPR responsive genes we have identified so far, the exception being the Cpn60/10 bidirectional promoter. Mutation of each of these elements substantially reduced the mtUPR responsiveness of the promoters suggesting that these elements coordinately regulate mtUPR

Biochemical characterization of Acacia schweinfurthii serine proteinase inhibitor

One of the many control mechanisms of serine proteinases is their specific inhibition by protein proteinase inhibitors. An extract of Acacia schweinfurthii was screened for potential serine proteinase inhibition. It was successfully purified to homogeneity by precipitating with 80% (v/v) acetone and sequential chromatographic steps, including ion-exchange, affinity purifica- Q2 tion and RP-HPLC. Reducing SDS-PAGE conditions revealed an inhibitor (ASTI) consisting of two polypeptide chains A and B of approximate molecular weights of 16 and 10 kDa, respectively, and under non-reducing conditions, 26 kDa was observed. The inhibitor was shown to inhibit bovine trypsin (Ki of 3.45 nM) at an approximate molar ratio of inhibitor: trypsin (1:1). The A- and B-chains revealed complete sequences of 140 and 40 amino acid residues, respectively. Sequence similarity (70%) was reported between ASTI A-chain and ACTI A-chain (Acacia confusa) using the ClustalW. The B-chain produced a 76% sequence similarity between ASTI and Leucaena leucocephala trypsin inhibitor