Connectivity-enhanced diffusion analysis reveals white matter density disruptions in first episode and chronic schizophrenia.

Reduced fractional anisotropy (FA) is a well-established correlate of schizophrenia, but it remains unclear whether these tensor-based differences are the result of axon damage and/or organizational changes and whether the changes are progressive in the adult course of illness. Diffusion MRI data were collected in 81 schizophrenia patients (54 first episode and 27 chronic) and 64 controls. Analysis of FA was combined with "fixel-based" analysis, the latter of which leverages connectivity and crossing-fiber information to assess both fiber bundle density and organizational complexity (i.e., presence and magnitude of off-axis diffusion signal). Compared with controls, patients with schizophrenia displayed clusters of significantly lower FA in the bilateral frontal lobes, right dorsal centrum semiovale, and the left anterior limb of the internal capsule. All FA-based group differences overlapped substantially with regions containing complex fiber architecture. FA within these clusters was positively correlated with principal axis fiber density, but inversely correlated with both secondary/tertiary axis fiber density and voxel-wise fiber complexity. Crossing fiber complexity had the strongest (inverse) association with FA (r = -0.82). When crossing fiber structure was modeled in the MRtrix fixel-based analysis pipeline, patients exhibited significantly lower fiber density compared to controls in the dorsal and posterior corpus callosum (central, postcentral, and forceps major). Findings of lower FA in patients with schizophrenia likely reflect two inversely related signals: reduced density of principal axis fiber tracts and increased off-axis diffusion sources. Whereas the former confirms at least some regions where myelin and or/axon count are lower in schizophrenia, the latter indicates that the FA signal from principal axis fiber coherence is broadly contaminated by macrostructural complexity, and therefore does not necessarily reflect microstructural group differences. These results underline the need to move beyond tensor-based models in favor of acquisition and analysis techniques that can help disambiguate different sources of white matter disruptions associated with schizophrenia

Synthesis and Functional Evaluation of DNA-Assembled Polyamidoamine Dendrimer Clusters for Cancer Cell-Specific Targeting

SummaryWe sought to produce dendrimers conjugated to different biofunctional moieties (fluorescein [FITC] and folic acid [FA]), and then link them together using complementary DNA oligonucleotides to produce clustered molecules that target cancer cells that overexpress the high-affinity folate receptor. Amine-terminated, generation 5 polyamidoamine (G5 PAMAM) dendrimers are first partially acetylated and then conjugated with FITC or FA, followed by the covalent attachment of complementary, 5′-phosphate-modified 34-base-long oligonucleotides. Hybridization of these oligonucleotide conjugates led to the self-assembly of the FITC- and FA-conjugated dendrimers. In vitro studies of the DNA-linked dendrimer clusters indicated specific binding to KB cells expressing the folate receptor. Confocal microscopy also showed the internalization of the dendrimer cluster. These results demonstrate the ability to design and produce supramolecular arrays of dendrimers using oligonucleotide bridges. This will also allow for further development of DNA-linked dendrimer clusters as imaging agents and therapeutics

The Evolution of Active Galactic Nuclei in Clusters of Galaxies to Redshift 1.3

We have measured the luminous active galactic nucleus (AGN) population in a large sample of clusters of galaxies and find evidence for a substantial increase in the cluster AGN population from z ~ 0.05 to z ~ 1.3. The present sample now includes 32 clusters of galaxies, including 15 clusters above z = 0.4, which corresponds to a three-fold increase compared to our previous work at high redshift. At z < 0.4, we have obtained new observations of AGN candidates in six additional clusters and found no new luminous AGN in cluster members. Our total sample of 17 low-redshift clusters contains only two luminous AGNs, while at high redshifts there are 18 such AGNs, or an average of more than one per cluster. We have characterized the evolution of luminous X-ray AGNs as the fraction of galaxies with M_R < M*_R (z) + 1 that host AGNs with rest-frame, hard X-ray [2-10 keV] luminosities L_X,H ≥ 10^43 erg s^–1. The AGN fraction increases from fA = 0.134^+0.18 _–0.087 % at a median z = 0.19 to fA = 1.00^+0.29 _–0.23 % at a median z = 0.72. Our best estimate of the evolution is a factor of 8 increase to z = 1 and the statistical significance of the increase is 3.8σ. This dramatic evolution is qualitatively similar to the evolution of the star-forming galaxy population in clusters known as the Butcher-Oemler effect. We discuss the implications of this result for the coevolution of black holes and galaxies in clusters, the evolution of AGN feedback, searches for clusters with the Sunyaev-Zel'dovich effect, and the possible detection of environment-dependent downsizing

SMART: Unique splitting-while-merging framework for gene clustering

Copyright @ 2014 Fa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Successful clustering algorithms are highly dependent on parameter settings. The clustering performance degrades significantly unless parameters are properly set, and yet, it is difficult to set these parameters a priori. To address this issue, in this paper, we propose a unique splitting-while-merging clustering framework, named “splitting merging awareness tactics” (SMART), which does not require any a priori knowledge of either the number of clusters or even the possible range of this number. Unlike existing self-splitting algorithms, which over-cluster the dataset to a large number of clusters and then merge some similar clusters, our framework has the ability to split and merge clusters automatically during the process and produces the the most reliable clustering results, by intrinsically integrating many clustering techniques and tasks. The SMART framework is implemented with two distinct clustering paradigms in two algorithms: competitive learning and finite mixture model. Nevertheless, within the proposed SMART framework, many other algorithms can be derived for different clustering paradigms. The minimum message length algorithm is integrated into the framework as the clustering selection criterion. The usefulness of the SMART framework and its algorithms is tested in demonstration datasets and simulated gene expression datasets. Moreover, two real microarray gene expression datasets are studied using this approach. Based on the performance of many metrics, all numerical results show that SMART is superior to compared existing self-splitting algorithms and traditional algorithms. Three main properties of the proposed SMART framework are summarized as: (1) needing no parameters dependent on the respective dataset or a priori knowledge about the datasets, (2) extendible to many different applications, (3) offering superior performance compared with counterpart algorithms.National Institute for Health Researc

Functionally relevant white matter degradation in multiple sclerosis: a tract-based spatial meta-analysis

Purpose To identify statistical consensus between published studies for distribution and functional relevance of tract white matter (WM) degradation in multiple sclerosis (MS). Materials and Methods By systematically searching online databases, tract-based spatial statistics studies were identified that compared fractional anisotropy (FA; a marker for WM integrity) in MS patients to healthy control subjects, correlated FA in MS patients with physical disability, or correlated FA in MS patients with cognitive performance. Voxelwise meta-analysis was performed by using the Signed Differential Mapping method for each comparison. Moderating effects of mean age, mean physical disability score, imager magnet strength, lesion load, and number of diffusion directions were assessed by means of meta-regression. Results Meta-analysis was performed on data from 495 patients and 253 control subjects across 12 studies. MS diagnosis was significantly associated with widespread lower tract FA (nine studies; largest cluster, 4379 voxels; z = 7.1; P < .001). Greater physical disability was significantly associated with lower FA in the right posterior cingulum, left callosal splenium, right inferior fronto-occipital fasciculus, and left fornix crus (six studies; 323 voxels; z = 1.7; P = .001). Impaired cognition was significantly associated with lower FA in the callosal genu, thalamus, right posterior cingulum, and fornix crus (seven studies; largest cluster, 980 voxels; z = 2.5; P < .001). Conclusion WM damage is widespread in MS with differential and only minimally overlapping distributions of low FA that relates to physical disability and cognitive impairment. The higher number of clusters of lower FA in relation to cognition and their higher z scores suggest that cerebral WM damage may have a greater relevance to cognitive dysfunction than physical disability in MS, and that low anterior callosal and thalamic FA have specific importance to cognitive status

A Search for Sub-Millisecond Pulsars

We have conducted a search of 19 southern Galactic globular clusters for sub-millisecond pulsars at 660 MHz with the Parkes 64-m radio telescope. To minimize dispersion smearing we used the CPSR baseband recorder, which samples the 20 MHz observing band at the Nyquist rate. By possessing a complete description of the signal we could synthesize an optimal filterbank in software, and in the case of globular clusters of known dispersion measure, much of the dispersion could be removed using coherent techniques. This allowed for very high time resolution (25.6 us in most cases), making our searches in general sensitive to sub-millisecond pulsars with flux densities greater than about 3 mJy at 50 cm. No new pulsars were discovered, placing important constraints on the proportion of pulsars with very short spin periods in these clusters.Comment: 8 pages, 3 figures, to appear in Ap

Improving speaker turn embedding by crossmodal transfer learning from face embedding

Learning speaker turn embeddings has shown considerable improvement in situations where conventional speaker modeling approaches fail. However, this improvement is relatively limited when compared to the gain observed in face embedding learning, which has been proven very successful for face verification and clustering tasks. Assuming that face and voices from the same identities share some latent properties (like age, gender, ethnicity), we propose three transfer learning approaches to leverage the knowledge from the face domain (learned from thousands of images and identities) for tasks in the speaker domain. These approaches, namely target embedding transfer, relative distance transfer, and clustering structure transfer, utilize the structure of the source face embedding space at different granularities to regularize the target speaker turn embedding space as optimizing terms. Our methods are evaluated on two public broadcast corpora and yield promising advances over competitive baselines in verification and audio clustering tasks, especially when dealing with short speaker utterances. The analysis of the results also gives insight into characteristics of the embedding spaces and shows their potential applications

First Measurement of a Rapid Increase in the AGN Fraction in High-Redshift Clusters of Galaxies

We present the first measurement of the AGN fraction in high-redshift clusters of galaxies (z~0.6) with spectroscopy of one cluster and archival data for three additional clusters. We identify 8 AGN in all four of these clusters from the Chandra data, which are sensitive to AGN with hard X-ray (2-10keV) luminosity L_{X,H} > 10^43 erg/s in host galaxies more luminous than a rest frame M_R < -20 mag. This stands in sharp contrast to the one AGN with L_{X,H} > 10^43 erg/s we discovered in our earlier study of eight low-redshift clusters with z=0.06-0.31 (average z~0.2). Three of the four high-redshift cluster datasets are sensitive to nearly L_{X,H} > 10^42 erg/s and we identify seven AGN above this luminosity limit, compared to two in eight, low-redshift clusters. Based on membership estimates for each cluster, we determine that the AGN fraction at z~0.6 is f_A(L_X>10^42;M_R<-20) = 0.028 (+0.019/-0.012) and f_A(L_X>10^43;M_R<-20) = 0.020 (+0.012/-0.008). These values are approximately a factor of 20 greater than the AGN fractions in lower-redshift (average z~0.2) clusters of galaxies and represent a substantial increase over the factors of 1.5 and 3.3 increase, respectively, in the measured space density evolution of the hard X-ray luminosity function over this redshift range. Potential systematic errors would only increase the significance of our result. The cluster AGN fraction increases more rapidly with redshift than the field and the increase in cluster AGN indicates the presence of an AGN Butcher-Oemler Effect.Comment: ApJL Accepted, 5 pages, 2 figure

Wave Packet Dynamics, Ergodicity, and Localization in Quasiperiodic Chains

In this paper, we report results for the wave packet dynamics in a class of quasiperiodic chains consisting of two types of weakly coupled clusters. The dynamics are studied by means of the return probability and the mean square displacement. The wave packets show anomalous diffusion in a stepwise process of fast expansion followed by time intervals of confined wave packet width. Applying perturbation theory, where the coupling parameter v is treated as perturbation, the properties of the eigenstates of the system are investigated and related to the structure of the chains. The results show the appearance of non-localized states only in sufficiently high orders of the perturbation expansions. Further, we compare these results to the exact solutions obtained by numerical diagonalization. This shows that eigenstates spread across the entire chain for v>0, while in the limit v->0 ergodicity is broken and eigenstates only spread across clusters of the same type, in contradistinction to trivial localization for v=0. Caused by this ergodicity breaking, the wave packet dynamics change significantly in the presence of an impurity offering the possibility to control its long-term dynamics.Comment: 10 pages, 9 figure