Data Integration And Targeted Anticancer Drug Synergies Prediction

In the past decades, targeted cancer therapies have made considerable achievements in inhibiting cancer progression by modulating specific molecular targets. However, targeted cancer therapies have reached a plateau of efficacy as the primary therapy since tumor cells can achieve adaptability through functional redundancies and activation of compensatory signaling pathways. Therapies using drug combinations have been developed to overcome the bottleneck. Accurate predictions of synergies effect can help prioritize biological experiments to identify effective combination therapies. Data integration can give us a deeper insight into the mechanism of cancer and drug synergies and help to address the challenge in prediction of drug combinations. In this thesis, we illustrate that integrative analysis of multiple types of omics data and pharmacological data can more effectively identify drug synergies, hence improve the prediction accuracy. As part of the AstraZeneca-Sanger Drug Combination Prediction DREAM Challenge, we showed that multiple data integration methods could identify multiple oncogenes and tumor suppressor genes as signature genes. We showed that several models built through data integration outperformed benchmark models without data integration methods

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

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

Comparative Study on the Choice of Muslim migrants Residence in Xi’an and Lanzhou Cities, China

Residential choice is one of the basic contents of urban adaptation of the floating population and an important aspect in determining the quality of life in the city. This study is for Muslim migrants with three attributes (minority, floating population and religious belief). The purpose is to reveal the commonalities and differences in the choice of living spaces of Muslim Migrants in multi-ethnic cities Lanzhou and Xi’an, to provide guidance for the targeted management of Muslim migrants and promote their urban integration. Based on available research data from 2017-2019, the study adopts spatial analysis and regression analysis to explore the results of the selection of Muslim migrants living space in two cities and its influencing factors. The main conclusions are as follows: 1) The commonality of Muslim migrants living space in the two cities lies in: the distribution pattern of “Living around the mosque and running business nearby the mosque” still exists. The living space of Muslim migrants consists of points (mosques), lines (streets or traffic lines), and faces (inhabited areas), forming a spatial distribution pattern of the “mosque + community” residential circle. Differences: Muslim migrants in Hui’s street, Xi’an, taking the “Mosque-alley system” as an independent social organization, and their living space presents a " mosque-alley Interlaced" distribution. Muslim migrants living in the urban village community on the periphery of Hui’s street take "mosque" and "farm market" as the dual core, showing the “core (mosque/market) + community” inlaid living space situation. The Muslim migrants in Lanzhou generally live around the mosque or close to the streets and roads that lead to mosque. 2). In terms of commonality, the living choices of Muslim migrants in both cities consider the distance from the place of work, the mosque or the Muslim community to the place of residence. In terms of differences, the residential choice of Muslim migrants in Xi’an is mainly influenced by the composition of the living, the income of wages, and the nature of the occupation. The choice is mainly influenced by the rent level, occupational nature and wage income of the house; and the main influencing factors of the choice of Muslim migrants in Lanzhou are the education level and the rent level of the house. The main influencing factors of residential location selection are education level and mobility purpose. The level of education, traditional living customs, and rent levels have become the core factors determining the urban accommodation adaptation of Muslim migrants

Adaptive Control of a Class of Switched Nonlinear System with Partial State Constraints Using a Barrier Lyapunov Function

This paper discusses partial state constraint adaptive tracking control problem of switched nonlinear systems with uncertain parameters. In order to ensure boundedness of the outputs and prevent the states from violating the constraints, a barrier Lyapunov function (BLF) is employed. Based on backstepping method, an adaptive controller for the switched system is designed. Furthermore, the state-constrained asymptotic tracking under arbitrary switching is performed. The closed-loop signals keep bounded when the initial states and control parameters are given. Finally, examples and simulation results are reported to illustrate the effectiveness of the proposed controller

Correlation-pattern-based Continuous-variable Entanglement Detection through Neural Networks

Entanglement in continuous-variable non-Gaussian states provides irreplaceable advantages in many quantum information tasks. However, the sheer amount of information in such states grows exponentially and makes a full characterization impossible. Here, we develop a neural network that allows us to use correlation patterns to effectively detect continuous-variable entanglement through homodyne detection. Using a recently defined stellar hierarchy to rank the states used for training, our algorithm works not only on any kind of Gaussian state but also on a whole class of experimentally achievable non-Gaussian states, including photon-subtracted states. With the same limited amount of data, our method provides higher accuracy than usual methods to detect entanglement based on maximum-likelihood tomography. Moreover, in order to visualize the effect of the neural network, we employ a dimension reduction algorithm on the patterns. This shows that a clear boundary appears between the entangled states and others after the neural network processing. In addition, these techniques allow us to compare different entanglement witnesses and understand their working. Our findings provide a new approach for experimental detection of continuous-variable quantum correlations without resorting to a full tomography of the state and confirm the exciting potential of neural networks in quantum information processing.Comment: 9 pages (incl. appendix), 6 figures, comments welcome