Sex-based differences in functional brain activity during working memory in survivors of pediatric acute lymphoblastic leukemia

BACKGROUND: Long-term survivors of pediatric acute lymphoblastic leukemia are at elevated risk for neurocognitive deficits and corresponding brain dysfunction. This study examined sex-based differences in functional neuroimaging outcomes in acute lymphoblastic leukemia survivors treated with chemotherapy alone. METHODS: Functional magnetic resonance imaging (fMRI) and neurocognitive testing were obtained in 123 survivors (46% male; median [min-max] age = 14.2 years [8.3-26.5 years]; time since diagnosis = 7.7 years [5.1-12.5 years]) treated on the St. Jude Total XV treatment protocol. Participants performed the n-back working memory task in a 3 T scanner. Functional neuroimaging data were processed (realigned, slice time corrected, normalized, smoothed) and analyzed using statistical parametric mapping with contrasts for 1-back and 2-back conditions, which reflect varying degrees of working memory and task load. Group-level fMRI contrasts were stratified by sex and adjusted for age and methotrexate exposure. Statistical tests were 2-sided (P \u3c .05 statistical significance threshold). RESULTS: Relative to males, female survivors exhibited less activation (ie, reduced blood oxygen dependent-level signals) in the right parietal operculum, supramarginal gyrus and inferior occipital gyrus, and bilateral superior frontal medial gyrus during increased working memory load (family-wise error-corrected P = .004 to .008, adjusting for age and methotrexate dose). Female survivors were slower to correctly respond to the 2-back condition than males (P \u3c .05), though there were no differences in overall accuracy. Performance accuracy was negatively correlated with fMRI activity in female survivors (Pearson\u27s r = -0.39 to -0.29, P = .001 to .02), but not in males. CONCLUSIONS: These results suggest the working memory network is more impaired in female survivors than male survivors, which may contribute to ongoing functional deficits

Discrete structure of ultrathin dielectric films and their surface optical properties

The boundary problem of linear classical optics about the interaction of electromagnetic radiation with a thin dielectric film has been solved under explicit consideration of its discrete structure. The main attention has been paid to the investigation of the near-zone optical response of dielectrics. The laws of reflection and refraction for discrete structures in the case of a regular atomic distribution are studied and the structure of evanescent harmonics induced by an external plane wave near the surface is investigated in details. It is shown by means of analytical and numerical calculations that due to the existence of the evanescent harmonics the laws of reflection and refraction at the distances from the surface less than two interatomic distances are principally different from the Fresnel laws. From the practical point of view the results of this work might be useful for the near-field optical microscopy of ultrahigh resolution.Comment: 25 pages, 16 figures, LaTeX2.09, to be published in Phys.Rev.

Automated ventricular systems segmentation in brain CT images by combining low-level segmentation and high-level template matching

<p>Abstract</p> <p>Background</p> <p>Accurate analysis of CT brain scans is vital for diagnosis and treatment of Traumatic Brain Injuries (TBI). Automatic processing of these CT brain scans could speed up the decision making process, lower the cost of healthcare, and reduce the chance of human error. In this paper, we focus on automatic processing of CT brain images to segment and identify the ventricular systems. The segmentation of ventricles provides quantitative measures on the changes of ventricles in the brain that form vital diagnosis information.</p> <p>Methods</p> <p>First all CT slices are aligned by detecting the ideal midlines in all images. The initial estimation of the ideal midline of the brain is found based on skull symmetry and then the initial estimate is further refined using detected anatomical features. Then a two-step method is used for ventricle segmentation. First a low-level segmentation on each pixel is applied on the CT images. For this step, both Iterated Conditional Mode (ICM) and Maximum A Posteriori Spatial Probability (MASP) are evaluated and compared. The second step applies template matching algorithm to identify objects in the initial low-level segmentation as ventricles. Experiments for ventricle segmentation are conducted using a relatively large CT dataset containing mild and severe TBI cases.</p> <p>Results</p> <p>Experiments show that the acceptable rate of the ideal midline detection is over 95%. Two measurements are defined to evaluate ventricle recognition results. The first measure is a sensitivity-like measure and the second is a false positive-like measure. For the first measurement, the rate is 100% indicating that all ventricles are identified in all slices. The false positives-like measurement is 8.59%. We also point out the similarities and differences between ICM and MASP algorithms through both mathematically relationships and segmentation results on CT images.</p> <p>Conclusion</p> <p>The experiments show the reliability of the proposed algorithms. The novelty of the proposed method lies in its incorporation of anatomical features for ideal midline detection and the two-step ventricle segmentation method. Our method offers the following improvements over existing approaches: accurate detection of the ideal midline and accurate recognition of ventricles using both anatomical features and spatial templates derived from Magnetic Resonance Images.</p

Intra-Organ Variation in Age-Related Mutation Accumulation in the Mouse

Using a transgenic mouse model harboring chromosomally integrated lacZ mutational target genes, we previously demonstrated that mutations accumulate with age much more rapidly in the small intestine than in the brain. Here it is shown that in the small intestine point mutations preferentially accumulate in epithelial cells of the mucosa scraped off the underlying serosa. The mucosal cells are the differentiated villus cells that have undergone multiple cell divisions. A smaller age-related increase, also involving genome rearrangements, was observed in the serosa, which consists mainly of the remaining crypts and non-dividing smooth muscle cells. In the brain we observed an accumulation of only point mutations in no other areas than hypothalamus and hippocampus. To directly test for cell division as the determining factor in the generation of point mutations we compared mutation induction between mitotically active and quiescent embryonic fibroblasts from the same lacZ mice, treated with either UV (a point mutagen) or hydrogen peroxide (a clastogen). The results indicate that while point mutations are highly replication-dependent, genome rearrangements are as easily induced in non-dividing cells as in mitotically active ones. This strongly suggests that the point mutations found to have accumulated in the mucosal part of the small intestine are the consequence of replication errors. The same is likely true for point mutations accumulating in hippocampus and hypothalamus of the brain since neurogenesis in these two areas continues throughout life. The observed intra-organ variation in mutation susceptibility as well as the variation in replication dependency of different types of mutations indicates the need to not only extend observations made on whole organs to their sub-structures but also take the type of mutations and mitotic activity of the cells into consideration. This should help elucidating the impact of genome instability and its consequences on aging and disease

Resolve and eco: the halo mass-dependent shape of galaxy stellar and baryonic mass functions

In this work, we present galaxy stellar and baryonic (stars plus cold gas) mass functions (SMF and BMF) and their halo mass dependence for two volume-limited data sets. The first, RESOLVE-B, coincides with the Stripe 82 footprint and is extremely complete down to baryonic mass Mbary ∼ 10^9.1 M⊙, probing the gas-rich dwarf regime below Mbary ∼ 10^10 M⊙. The second, ECO, covers a ~40× larger volume (containing RESOLVE-A) and is complete to Mbary ~10^9.4 M⊙. To construct the SMF and BMF we implement a new “cross-bin sampling” technique with Monte Carlo sampling from the full likelihood distributions of stellar or baryonic mass. Our SMFs exhibit the “plateau” feature starting below Mstar ~10^10 M⊙ that has been described in prior work. However, the BMF fills in this feature and rises as a straight power law below ~10^10 M⊙, as gas-dominated galaxies become the majority of the population. Nonetheless, the low-mass slope of the BMF is not as steep as that of the theoretical dark matter halo MF. Moreover, we assign group halo masses by abundance matching, finding that the SMF and BMF separated into four physically motivated halo mass regimes reveal complex structure underlying the simple shape of the overall MFs. In particular, the satellite MFs are depressed below the central galaxy MF “humps” in groups with mass < 10^13.5 M⊙ yet rise steeply in clusters. Our results suggest that satellite destruction and/or stripping are active from the point of nascent group formation. We show that the key role of groups in shaping MFs enables reconstruction of a given survey’s SMF or BMF based on its group halo mass distribution

CD34+/M-cadherin+ Bone Marrow Progenitor Cells Promote Arteriogenesis in Ischemic Hindlimbs of ApoE−/− Mice

BACKGROUND: Cell-based therapy shows promise in treating peripheral arterial disease (PAD); however, the optimal cell type and long-term efficacy are unknown. In this study, we identified a novel subpopulation of adult progenitor cells positive for CD34 and M-cadherin (CD34⁺/M-cad⁺ BMCs) in mouse and human bone marrow. We also examined the long-lasting therapeutic efficacy of mouse CD34⁺/M-cad⁺ BMCs in restoring blood flow and promoting vascularization in an atherosclerotic mouse model of PAD. METHODS AND FINDINGS: Colony-forming cell assays and flow cytometry analysis showed that CD34⁺/M-cad⁺ BMCs have hematopoietic progenitor properties. When delivered intra-arterially into the ischemic hindlimbs of ApoE⁻/⁻ mice, CD34⁺/M-cad⁺ BMCs alleviated ischemia and significantly improved blood flow compared with CD34⁺/M-cad⁻ BMCs, CD34⁻/M-cad⁺ BMCs, or unselected BMCs. Significantly more arterioles were seen in CD34⁺/M-cad⁺ cell-treated limbs than in any other treatment group 60 days after cell therapy. Furthermore, histologic assessment and morphometric analyses of hindlimbs treated with GFP⁺ CD34⁺/M-cad⁺ cells showed that injected cells incorporated into solid tissue structures at 21 days. Confocal microscopic examination of GFP⁺ CD34⁺/M-cad⁺ cell-treated ischemic legs followed by immunostaining indicated the vascular differentiation of CD34⁺/M-cad⁺ progenitor cells. A cytokine antibody array revealed that CD34⁺/M-cad⁺ cell-conditioned medium contained higher levels of cytokines in a unique pattern, including bFGF, CRG-2, EGF, Flt-3 ligand, IGF-1, SDF-1, and VEGFR-3, than did CD34⁺/M-cad⁻ cell-conditioned medium. The proangiogenic cytokines secreted by CD34⁺/M-cad⁺ cells induced oxygen- and nutrient-depleted endothelial cell sprouting significantly better than CD34⁺/M-cad⁻ cells during hypoxia. CONCLUSION: CD34⁺/M-cad⁺ BMCs represent a new progenitor cell type that effectively alleviates hindlimb ischemia in ApoE⁻/⁻ mice by consistently improving blood flow and promoting arteriogenesis. Additionally, CD34⁺/M-cad⁺ BMCs contribute to microvascular remodeling by differentiating into vascular cells and releasing proangiogenic cytokines and growth factors

Angular Momentum of Early- and Late-type Galaxies: Nature or Nurture?

We investigate the origin, the shape, the scatter, and the cosmic evolution in the observed relationship between specific angular momentum $j_\star$ and the stellar mass $M_\star$ in early-type (ETGs) and late-type galaxies (LTGs). Specifically, we exploit the observed star-formation efficiency and chemical abundance to infer the fraction f_\rm inf of baryons that infall toward the central regions of galaxies where star formation can occur. We find f_\rm inf\approx 1 for LTGs and $\approx 0.4$ for ETGs with an uncertainty of about $0.25$ dex, consistent with a biased collapse. By comparing with the locally observed $j_\star$ vs. $M_\star$ relations for LTGs and ETGs we estimate the fraction $f_j$ of the initial specific angular momentum associated to the infalling gas that is retained in the stellar component: for LTGs we find $f_j\approx 1.11^+0.75_-0.44$, in line with the classic disc formation picture; for ETGs we infer $f_j\approx 0.64^+0.20_-0.16$, that can be traced back to a $z<1$ evolution via dry mergers. We also show that the observed scatter in the $j_\star$ vs. $M_\star$ relation for both galaxy types is mainly contributed by the intrinsic dispersion in the spin parameters of the host dark matter halo. The biased collapse plus mergers scenario implies that the specific angular momentum in the stellar components of ETG progenitors at $z\sim 2$ is already close to the local values, in pleasing agreement with observations. All in all, we argue such a behavior to be imprinted by nature and not nurtured substantially by the environment

Subhaloes gone Notts: subhaloes as tracers of the dark matter halo shape

We study the shapes of subhalo distributions from four dark-matter-only simulations of Milky Way-type haloes. Comparing the shapes derived from the subhalo distributions at high resolution to those of the underlying dark matter fields, we find the former to be more triaxial if the analysis is restricted to massive subhaloes. For three of the four analysed haloes, the increased triaxiality of the distributions of massive subhaloes can be explained by a systematic effect caused by the low number of objects. Subhaloes of the fourth halo show indications for anisotropic accretion via their strong triaxial distribution and orbit alignment with respect to the dark matter field. These results are independent of the employed subhalo finder. Comparing the shape of the observed Milky Way satellite distribution to those of high-resolution subhalo samples from simulations, we find agreement for samples of bright satellites, but significant deviations if faint satellites are included in the analysis. These deviations might result from observational incompleteness