Constructing a Non-Negative Low Rank and Sparse Graph with Data-Adaptive Features

This paper aims at constructing a good graph for discovering intrinsic data structures in a semi-supervised learning setting. Firstly, we propose to build a non-negative low-rank and sparse (referred to as NNLRS) graph for the given data representation. Specifically, the weights of edges in the graph are obtained by seeking a nonnegative low-rank and sparse matrix that represents each data sample as a linear combination of others. The so-obtained NNLRS-graph can capture both the global mixture of subspaces structure (by the low rankness) and the locally linear structure (by the sparseness) of the data, hence is both generative and discriminative. Secondly, as good features are extremely important for constructing a good graph, we propose to learn the data embedding matrix and construct the graph jointly within one framework, which is termed as NNLRS with embedded features (referred to as NNLRS-EF). Extensive experiments on three publicly available datasets demonstrate that the proposed method outperforms the state-of-the-art graph construction method by a large margin for both semi-supervised classification and discriminative analysis, which verifies the effectiveness of our proposed method

OVERCOMING THE AGE-ASSOCIATED DECLINE IN NEURAL STEM CELL PROLIFERATION

poster abstractThe U.S. population is aging. Age-related cognitive decline is a major public health problem. Developing an approach to treat or delay cognitive decline is critical. Neurogenesis by neural stem/progenitor cells (NSCs) in the hippocampus is related to cognitive function, and is greatly affected by the aging process. The molecular signaling that regulates age-related decline in neurogenesis is still poorly understood. Here we took the advantage of a transgenic mouse, Nestin-GFP, to assess neurogenesis and molecular signal-ing related to age-related decline in neurogenesis. We found that the total number of NSCs, including quiescent neural progenitors (QNPs) and amplify-ing neural progenitors (ANPs) decreased as the mice aged, but more im-portantly, ANPs are more significantly affected than QNPs, leading to further reduction in number and proliferation of ANPs. We further found that the mTOR signaling pathway is impaired in NSCs as mice age. Activating the mTOR signaling pathway through Ketamine injections increased NSC prolif-eration in aged mice. In contrast, inhibiting the activity of the mTOR signal-ing pathway by rapamycin is sufficient to reduce ANP proliferation in young mice. These results indicate that NSCs becomes more quiescent when the activity of mTOR signaling is compromised in aged mice, and stimulating the activity of mTOR signaling can overcome the age-associated decline in NSC proliferation. This data suggests that promoting stem cell proliferation to en-hance neurogenesis may be a potential approach for attenuating cognitive decline in the aging brain.This work was supported by funding from the Ralph W. and Grace M. Showalter Research Award, Indiana University Biological Research Grant, NIH grants RR025761 and 1R21NS072631-01A, and Undergraduate Research Opportunities Program (UROP)

NEROPATHOLOGICAL APPROACH FOR BLAST-WAVE INDUCED MILD BRAIN INJURY

poster abstractVeterans of Iraq and Afghanistan are extremely susceptible to complica-tions derived from blast-wave induced mild traumatic brain injury (mTBI) sustained from road-side bombs and IEDs. Furthermore, there are 1.5 mil-lion civilian incidences of TBIs annually in the United States, and as many as nearly 75% of them are mTBIs. An mTBI is an important medical concern because it can lead to long-term cognitive, emotional difficulties and behav-ioral disturbances. Neuroimaging with CT or MRI is usually negative. That is why mTBI has been called an “invisible wound.” There are no effective treatments for these disorders, partially due to the fact that the pathological basis leading to neurological disorders are poorly understood. Using a blast-wave injury model, several mice were given injuries similar to those from the front lines. The damaged brains were collected, mounted, stained, and imaged to track the dendrite and spine degeneration, both over all and by type of spine. After quantification, the results showed that the injured brain is intact without showing dramatic lesion or cell death, however, when we further assessed the morphologies of the spared neurons by using Golgi staining to visualize the individual neurons including their processes and spines in a very high resolution, we found that the dendrites of the spared neurons in the injured cortex demonstrated dramatic swelling with beading, a hallmark of dendritic injury, and there was a significant decrease in the number of mature (mushroom) spines, as well as a significant decrease in the overall number of spines. The function of the central nervous system critically relies on the synaptic connection from the different neurons be-tween the spines. The widespread synapse loss disrupts neural circuitry fol-lowing mTBI and will certainly contribute to neurological disorders. Our re-sults showed that mild blast-wave induced injury led to extensive dendrite degeneration and synapse reduction in the cortex in an animal model. This experimental study sheds light on the neuropathology of mild TBI in humans, and suggests that neurodegeneration may be a novel target for developing diagnostic methods and therapeutic approaches for mTBI in the future

TRAUMATIC BRAIN INJURY LEADS TO ABERRANT MIGRATION OF ADULT-BORN NEURONS IN THE HIPPOCAMPUS

poster abstractTraumatic brain injury (TBI) is the leading cause of death in children and young adults, leading to substantial cognitive impairment, motor dysfunction and epilepsy. There is no effective treatment for these dis-orders. The discovery of neural stem/progenitor cells (NSCs) in the adult brain raises a potentially promising strategy for repairing CNS in-jury.Our previous study showed that TBI promotes NSC proliferation in an attempt to initiate innate repair and/or plasticity mechanisms. However, the spontaneously post-traumatic recovery of hippocampal-related cognitive and memory functions is very limited. Better under-standing of neurogenesis following TBI may provide additional inter-vention to further enhance neurogenesis for successfully repairing the damaged brain following TBI. Although newborn neurons generated from NSCs are continuously added to the brain throughout our life, they must migrate from their birthplace to their appropriate destina-tion to develop into mature neurons. When we tracked the migration of newly generated neurons in the adult hippocampus after TBI, we found that a large percentage of immature neurons migrate pass their normal stopping site at the inner granular cell layer, and misplace in the outer granular cell layer of the hippocampal dentate gyrus. The aberrant migration of adult-born neurons in the hippocampus occurs 3 days after TBI, and lasts for 10 weeks, resulting in a great number of newly generated neurons misplaced in the outer granular layer in the hippocampus. The newborn neurons at the displaced position will not be able to make correct connections with their appropriate targets, and may even make wrong connections with inappropriate nearby tar-gets in the pre-existing neural network. Abnormal migration can cause several diseases including epilepsy. These results suggest that stimu-lation of endogenous adult neural stem cells following TBI might offer new avenues for cell-based therapy. Additional intervention is required to further enhance successful neurogenesis for repairing the damaged brain

Finding Global Optimum for Truth Discovery: Entropy Based Geometric Variance

Truth Discovery is an important problem arising in data analytics related fields such as data mining, database, and big data. It concerns about finding the most trustworthy information from a dataset acquired from a number of unreliable sources. Due to its importance, the problem has been extensively studied in recent years and a number techniques have already been proposed. However, all of them are of heuristic nature and do not have any quality guarantee. In this paper, we formulate the problem as a high dimensional geometric optimization problem, called Entropy based Geometric Variance. Relying on a number of novel geometric techniques (such as Log-Partition and Modified Simplex Lemma), we further discover new insights to this problem. We show, for the first time, that the truth discovery problem can be solved with guaranteed quality of solution. Particularly, we show that it is possible to achieve a (1+eps)-approximation within nearly linear time under some reasonable assumptions. We expect that our algorithm will be useful for other data related applications

The Role of 7,8-Dihydroxyflavone in Preventing Dendrite Degeneration in Cortex After Moderate Traumatic Brain Injury

Our previous research showed that traumatic brain injury (TBI) induced by controlled cortical impact (CCI) not only causes massive cell death, but also results in extensive dendrite degeneration in those spared neurons in the cortex. Cell death and dendrite degeneration in the cortex may contribute to persistent cognitive, sensory, and motor dysfunction. There is still no approach available to prevent cells from death and dendrites from degeneration following TBI. When we treated the animals with a small molecule, 7,8-dihydroxyflavone (DHF) that mimics the function of brain-derived neurotrophic factor (BDNF) through provoking TrkB activation reduced dendrite swellings in the cortex. DHF treatment also prevented dendritic spine loss after TBI. Functional analysis showed that DHF improved rotarod performance on the third day after surgery. These results suggest that although DHF treatment did not significantly reduced neuron death, it prevented dendrites from degenerating and protected dendritic spines against TBI insult. Consequently, DHF can partially improve the behavior outcomes after TBI

Traumatic Brain Injury Stimulates Neural Stem Cell Proliferation via Mammalian Target of Rapamycin Signaling Pathway Activation

Neural stem cells in the adult brain possess the ability to remain quiescent until needed in tissue homeostasis or repair. It was previously shown that traumatic brain injury (TBI) stimulated neural stem cell (NSC) proliferation in the adult hippocampus, indicating an innate repair mechanism, but it is unknown how TBI promotes NSC proliferation. In the present study, we observed dramatic activation of mammalian target of rapamycin complex 1 (mTORC1) in the hippocampus of mice with TBI from controlled cortical impact (CCI). The peak of mTORC1 activation in the hippocampal subgranular zone, where NSCs reside, is 24-48 h after trauma, correlating with the peak of TBI-enhanced NSC proliferation. By use of a Nestin-GFP transgenic mouse, in which GFP is ectopically expressed in the NSCs, we found that TBI activated mTORC1 in NSCs. With 5-bromo-2'-deoxyuridine labeling, we observed that TBI increased mTORC1 activation in proliferating NSCs. Furthermore, administration of rapamycin abolished TBI-promoted NSC proliferation. Taken together, these data indicate that mTORC1 activation is required for NSC proliferation postinjury, and thus might serve as a therapeutic target for interventions to augment neurogenesis for brain repair after TBI

Delayed and progressive damages to juvenile mice after moderate traumatic brain injury

Symptoms are commonly more severe in pediatric traumatic brain injury (TBI) patients than in young adult TBI patients. To understand the mechanism, juvenile mice received a controlled cortical impact (CCI) injury at moderate level. Tissue lesion and cell death were measured and compared to our previous reports on brain injury in the young adult mice that received same level of impact using same injury device. Tissue lesion and cell death in the cortex was much less in the juvenile mouse brain in the first few hours after injury. However, once the injury occurred, it developed more rapidly, lasted much longer, and eventually led to exaggerated cell death and a 32.7% larger tissue lesion cavity in the cortex of juvenile mouse brain than of young adult mouse brain. Moreover, we found significant cell death in the thalamus of juvenile brains at 72 h, which was not commonly seen in the young adult mice. In summary, cell death in juvenile mice was delayed, lasted longer, and finally resulted in more severe brain injury than in the young adult mice. The results suggest that pediatric TBI patients may have a longer therapeutic window, but they also need longer intensive clinical care after injury

An Optimal Method for Diffusion Parameters of Nonlinear Diffusion Problem of Drug Releasing in 2D-Disc Device by Separate Variable Method

An optimization control model and the corresponding computational method drawing the diffusion parameters of the nonlinear problem for the drug releasing in the 2D-disc device were given in this paper. Firstly, based on the nonlinear diffusion equation of the drug releasing in the 2D-disc device, we used the linear diffusion problem to discrete the nonlinear diffusion problem with the discrete space and the discrete time. Then, by the separate variable method, the solution of the linear problem was given. Next, the least square method based on the separate variable idea (LSMSV) was used to estimate the nonlinear appropriate diffusion parameters. Finally, a numerical example was presented to show that the control model and the numerical method were valid for computing the diffusion coefficient of the nonlinear problem for the drug releasing in the 2D-disc device

Aging impairs dendrite morphogenesis of newborn neurons and is rescued by 7, 8-dihydroxyflavone

All aging individuals will develop some degree of decline in cognitive capacity as time progresses. The molecular and cellular mechanisms leading to age-related cognitive decline are still not fully understood. Through our previous research, we discovered that active neural progenitor cells selectively become more quiescent in response to aging, thus leading to the decline of neurogenesis in the aged hippocampus. Here, we further find that aging impaired dendrite development of newborn neurons. Currently, no effective approach is available to increase neurogenesis or promote dendrite development of newborn neurons in the aging brain. We found that systemically administration of 7, 8-dihydroxyflavone (DHF), a small molecule imitating brain-derived neurotrophic factor (BDNF), significantly enhanced dendrite length in the newborn neurons, while it did not promote survival of immature neurons, in the hippocampus of 12-month-old mice. DHF-promoted dendrite development of newborn neurons in the hippocampus may enhance their function in the aging animal leading to a possible improvement in cognition