VASCULAR INJURY IN Col3a1+/- MICE MODEL OF VASCULAR EHLER-DANLOS SYNDROME

Vascular type of Ehlers-Danlos Syndrome (vEDS) is an inherited cardiovascular disease affecting the middle to large sized arteries, with an incidence rate of 1/5000. vEDS patients also show a significant phenotype of easily bruised skin, indicating aberrant wound healing and injury repair ability. Over 70% of the patients carry a glycine mutation located in their COL3A1 gene, which encodes the propeptide of type III collagen. Mutations in glycine residues lead to a disruption in the assembly and maturation of type III collagen. The goal and significance of the current study was to investigate the potential role of COL3A1 haploinsufficiency in the development of vEDS and develop new potential therapies for vEDS patients. Carotid ligation was applied to the Col3a1+/- mouse as an injury model, and the results confirm that Col3a1+/- mice have aberrant arterial injury repair. Arteries from the injured Col3a1+/- mice showed increased cell proliferation, inflammation, and neovessel formation. In vitro, fibroblasts explanted from Col3a1+/- mice have persistent myofibroblast status after treatment with TGF-β1, which validates the in vivo findings. Finally, two treatments were tested on Col3a1+/- mice after carotid ligation: bone marrow transplantation and celiprolol. Transplantation of Col3a1+/+ bone marrow to Col3a1+/- mice corrects the post-injury phenotypes, suggesting that bone marrow derived fibrocytes can be differentiated into myofibroblasts and produce sufficient type III collagen for successful wound healing. Celiprolol treatment on the Col3a1+/- mice also corrects the wound healing impairment by decreasing inflammation and cell proliferation. Therefore, this study validates a novel paradigm for vEDS that decreased supply of mature type III collagen fibrils affects fibroblasts in arterial wound healing and also provides evidence for bone marrow transplantation and celiprolol as potential new therapeutic approaches to the treatment of vEDS patients

Predicting Flux And Pressure Relationships of Large Scale Filtration with USD Model Inputs: Method and application

Ultra Scale-Down tools have demonstrated the huge benefit for rapid process development with reduced material requirement and better solutions. In this poster, a method was reported to predict the flux and transmembrane pressure relationships of a diafiltration application for a crossflow filtration (CFF) process, based on data generated using an Ultra Scale-Down (USD) device that uses dead-end mode of operation to mimic CFF. A new flux prediction protocol was developed to accurately determine the system resistance of large scale crossflow filtration (CFF) systems, and, to predict CFF performance using USD data. Antibody fragment (Fab’) is expressed in E. coli as an intracellular product and E.coli homogenate was used for scale-up studies and to validate the prediction results. Predicted and actual flux-pressure drop and transmission data showed good agreement. Wall shear rate correlations have been established for both the lab scale cassette and the USD device, and a mimic has been developed by operating both scales at equivalent membrane averaged shear rates

Industrial metal pollution in water and probabilistic assessment of human health risk

© 2016 Elsevier Ltd Concentration of eight heavy metals in surface and groundwater around Dhaka Export Processing Zone (DEPZ) industrial area were investigated, and the health risk posed to local children and adult residents via ingestion and dermal contact was evaluated using deterministic and probabilistic approaches. Metal concentrations (except Cu, Mn, Ni, and Zn) in Bangshi River water were above the drinking water quality guidelines, while in groundwater were less than the recommended limits. Concentration of metals in surface water decreased as a function of distance. Estimations of non-carcinogenic health risk for surface water revealed that mean hazard index (HI) values of As, Cr, Cu, and Pb for combined pathways (i.e., ingestion and dermal contact) were >1.0 for both age groups. The estimated risk mainly came from the ingestion pathway. However, the HI values for all the examined metals in groundwater were 1 × 10−4 for adult and children, respectively. Deterministic and probabilistic estimations of cancer risk through exposure to groundwater were well below the safety limit. Overall, the population exposed to Bangshi River water remained at carcinogenic and non-carcinogenic health threat and the risk was higher for adults. Sensitivity analysis identified exposure duration (ED) and ingestion rate (IR) of water as the most relevant variables affecting the probabilistic risk estimation model outcome

Privacy-Preserving Outsourcing of Large-Scale Nonlinear Programming to the Cloud

The increasing massive data generated by various sources has given birth to big data analytics. Solving large-scale nonlinear programming problems (NLPs) is one important big data analytics task that has applications in many domains such as transport and logistics. However, NLPs are usually too computationally expensive for resource-constrained users. Fortunately, cloud computing provides an alternative and economical service for resource-constrained users to outsource their computation tasks to the cloud. However, one major concern with outsourcing NLPs is the leakage of user's private information contained in NLP formulations and results. Although much work has been done on privacy-preserving outsourcing of computation tasks, little attention has been paid to NLPs. In this paper, we for the first time investigate secure outsourcing of general large-scale NLPs with nonlinear constraints. A secure and efficient transformation scheme at the user side is proposed to protect user's private information; at the cloud side, generalized reduced gradient method is applied to effectively solve the transformed large-scale NLPs. The proposed protocol is implemented on a cloud computing testbed. Experimental evaluations demonstrate that significant time can be saved for users and the proposed mechanism has the potential for practical use.Comment: Ang Li and Wei Du equally contributed to this work. This work was done when Wei Du was at the University of Arkansas. 2018 EAI International Conference on Security and Privacy in Communication Networks (SecureComm

The promoters of human cell cycle genes integrate signals from two tumor suppressive pathways during cellular transformation

Deciphering regulatory events that drive malignant transformation represents a major challenge for systems biology. Here we analyzed genome-wide transcription profiling of an in-vitro transformation process. We focused on a cluster of genes whose expression levels increased as a function of p53 and p16INK4A tumor suppressors inactivation. This cluster predominantly consists of cell cycle genes and constitutes a signature of a diversity of cancers. By linking expression profiles of the genes in the cluster with the dynamic behavior of p53 and p16INK4A, we identified a promoter architecture that integrates signals from the two tumor suppressive channels and that maps their activity onto distinct levels of expression of the cell cycle genes, which in turn, correspond to different cellular proliferation rates. Taking components of the mitotic spindle as an example, we experimentally verified our predictions that p53-mediated transcriptional repression of several of these novel targets is dependent on the activities of p21, NFY and E2F. Our study demonstrates how a well-controlled transformation process allows linking between gene expression, promoter architecture and activity of upstream signaling molecules.Comment: To appear in Molecular Systems Biolog

Tag-Aware Recommender Systems: A State-of-the-art Survey

In the past decade, Social Tagging Systems have attracted increasing attention from both physical and computer science communities. Besides the underlying structure and dynamics of tagging systems, many efforts have been addressed to unify tagging information to reveal user behaviors and preferences, extract the latent semantic relations among items, make recommendations, and so on. Specifically, this article summarizes recent progress about tag-aware recommender systems, emphasizing on the contributions from three mainstream perspectives and approaches: network-based methods, tensor-based methods, and the topic-based methods. Finally, we outline some other tag-related works and future challenges of tag-aware recommendation algorithms.Comment: 19 pages, 3 figure

Substrate-induced band gap opening in epitaxial graphene

Graphene has shown great application potentials as the host material for next generation electronic devices. However, despite its intriguing properties, one of the biggest hurdles for graphene to be useful as an electronic material is its lacking of an energy gap in the electronic spectra. This, for example, prevents the use of graphene in making transistors. Although several proposals have been made to open a gap in graphene's electronic spectra, they all require complex engineering of the graphene layer. Here we show that when graphene is epitaxially grown on the SiC substrate, a gap of ~ 0.26 is produced. This gap decreases as the sample thickness increases and eventually approaches zero when the number of layers exceeds four. We propose that the origin of this gap is the breaking of sublattice symmetry owing to the graphene-substrate interaction. We believe our results highlight a promising direction for band gap engineering of graphene.Comment: 10 pages, 4 figures; updated reference

CD20 and CD19 targeted vectors induce minimal activation of resting B lymphocytes

B lymphocytes are an important cell population of the immune system. However, until recently it was not possible to transduce resting B lymphocytes with retro- or lentiviral vectors, making them unsusceptible for genetic manipulations by these vectors. Lately, we demonstrated that lentiviral vectors pseudotyped with modified measles virus (MV) glycoproteins hemagglutinin, responsible for receptor recognition, and fusion protein were able to overcome this transduction block. They use either the natural MV receptors, CD46 and signaling lymphocyte activation molecule (SLAM), for cell entry (MV-LV) or the vector particles were further modified to selectively enter via the CD20 molecule, which is exclusively expressed on B lymphocytes (CD20-LV). It has been shown previously that transduction by MV-LV does not induce B lymphocyte activation. However, if this is also true for CD20-LV is still unknown. Here, we generated a vector specific for another B lymphocyte marker, CD19, and compared its ability to transduce resting B lymphocytes with CD20-LV. The vector (CD19ds-LV) was able to stably transduce unstimulated B lymphocytes, albeit with a reduced efficiency of about 10% compared to CD20-LV, which transduced about 30% of the cells. Since CD20 as well as CD19 are closely linked to the B lymphocyte activation pathway, we investigated if engagement of CD20 or CD19 molecules by the vector particles induces activating stimuli in resting B lymphocytes. Although, activation of B lymphocytes often involves calcium influx, we did not detect elevated calcium levels. However, the activation marker CD71 was substantially up-regulated upon CD20-LV transduction and most importantly, B lymphocytes transduced with CD20-LV or CD19ds-LV entered the G1b phase of cell cycle, whereas untransduced or MV-LV transduced B lymphocytes remained in G0. Hence, CD20 and CD19 targeting vectors induce activating stimuli in resting B lymphocytes, which most likely renders them susceptible for lentiviral vector transduction

Electronic stress tensor analysis of hydrogenated palladium clusters

We study the chemical bonds of small palladium clusters Pd_n (n=2-9) saturated by hydrogen atoms using electronic stress tensor. Our calculation includes bond orders which are recently proposed based on the stress tensor. It is shown that our bond orders can classify the different types of chemical bonds in those clusters. In particular, we discuss Pd-H bonds associated with the H atoms with high coordination numbers and the difference of H-H bonds in the different Pd clusters from viewpoint of the electronic stress tensor. The notion of "pseudo-spindle structure" is proposed as the region between two atoms where the largest eigenvalue of the electronic stress tensor is negative and corresponding eigenvectors forming a pattern which connects them.Comment: 22 pages, 13 figures, published online, Theoretical Chemistry Account