Computational Molecular Design Using Tabu Search

The focus of this project is the use of computational molecular design (CMD) in the design of novel crosslinked polymers. A design example was completed for a dimethacrylate as part of a comonomer used in dental restoration, with the goal to create a dental adhesive with a longer clinical lifetime than those already on the market. The CMD methodology begins with the calculation of molecular descriptors that describe the crosslinked polymer structure. Connectivity index are used as the primary set of descriptors, and have been used successfully in other CMD projects. Quantitative structure property relationships (QSPRs) were developed relating the structural descriptors to the experimentally collected property data. Models were chosen using Mallows' Cp with correlation coefficient significance. Desirable target property values were chosen which lead to an improved clinical lifetime. Structural constraints were defined to increase stability and ease of synthesis. The Tabu Search optimization algorithm was used to design polymers with desirable properties. Finally, a prediction interval was calculated for each candidate to represent the possible error in the predicted properties. The described methodology provides a list of candidate monomers with predicted properties near the desired target values, which are selected such that the adhesives will show improved propertoes relative to the standard HEMA/BisGMA formulation. The methodology can be easily altered to allow for additional property calculations and structural constraints. This methodology can also be used for molecular design projects beyond crosslinked polymers

Increasing Inter-Modal Access to Transit: Phase II

Phase II of the two part study assess pedestrian and bicycle accessibility in the areas surrounding Ardmore Junction, Avondale park and Ride, and Lindenwold Station using PLOS and BLOS software. Field views were conducted to collect data and assess non-motorized mobility enhancements supporting station access. The analysis revealed that even where pedestrian access within a quarter mile radius was acceptable, bicycle access within a mile radius may be unacceptable. The Absence of road buffers along sidewalks, visible striping at intersections, and appropriate bicycle racks at stations all degrade the non-motorized travel environment. Improvements in the buffering, striping, and bicycle racks at stations and their surrounding areas would do a lot to improve the non-motorized access and use of transit stations

Chester Riverfront and Community Rail Access Study

This study examined connecting SEPTA's Wilmington-Newark regional rail line with existing and planned development along the Chester City Riverfront. Three alternatives were considered for connecting the regional rail service and the Chester City Riverfront: retain, replace, or relocate the Highland Avenue Station. Construction costs ranged from $17 to$27 million, depending on the strategy. It was determined that the current Highland Avenue Station would necessitate closure in 3 to 5 years based on structural safety concerns. Based on the factors outlined, it is suggested that Townsend/Engle or a new station at Highland Avenue appear to be the best choices, with the possibility of keeping Flower Street as another option. The details of land acquisition, design, and construction still need to be worked out between land owners, Chester City and SEPTA. The report informs the policy conversation and narrows possible locations for further engineering study

Homotopic functional connectivity disruptions in glioma patients are associated with tumor malignancy and overall survival

BACKGROUND: Gliomas exhibit widespread bilateral functional connectivity (FC) alterations that may be associated with tumor grade. Limited studies have examined the connection-level mechanisms responsible for these effects. Given the typically strong FC observed between mirroring/homotopic brain regions in healthy subjects, we hypothesized that homotopic connectivity (HC) is altered in low-grade and high-grade glioma patients and the extent of disruption is associated with tumor grade and predictive of overall survival (OS) in a cohort of METHODS: We used a mirrored FC-derived cortical parcellation to extract blood-oxygen-level-dependent (BOLD) signals and to quantify FC differences between homotopic pairs in normal-appearing brain in a retrospective cohort of glioma patients and healthy controls. RESULTS: Fifty-nine glioma patients (WHO grade 2, CONCLUSIONS: These findings demonstrate an association between tumor grade and HC alterations that may underlie global FC changes and provide prognostic information

Functional connectivity within glioblastoma impacts overall survival

BACKGROUND: Glioblastoma (GBM; World Health Organization grade IV) assumes a variable appearance on MRI owing to heterogeneous proliferation and infiltration of its cells. As a result, the neurovascular units responsible for functional connectivity (FC) may exist within gross tumor boundaries, albeit with altered magnitude. Therefore, we hypothesize that the strength of FC within GBMs is predictive of overall survival. METHODS: We used predefined FC regions of interest (ROIs) in de novo GBM patients to characterize the presence of within-tumor FC observable via resting-state functional MRI and its relationship to survival outcomes. RESULTS: Fifty-seven GBM patients (mean age, 57.8 ± 13.9 y) were analyzed. Functionally connected voxels, not identifiable on conventional structural images, can be routinely found within the tumor mass and was not significantly correlated to tumor size. In patients with known survival times (n = 31), higher intranetwork FC strength within GBM tumors was associated with better overall survival even after accounting for clinical and demographic covariates. CONCLUSIONS: These findings suggest the possibility that functionally intact regions may persist within GBMs and that the extent to which FC is maintained may carry prognostic value and inform treatment planning

Dynamics of DNA replication loops reveal temporal control of lagging-strand synthesis

In all organisms, the protein machinery responsible for the replication of DNA, the replisome, is faced with a directionality problem. The antiparallel nature of duplex DNA permits the leading-strand polymerase to advance in a continuous fashion, but forces the lagging-strand polymerase to synthesize in the opposite direction. By extending RNA primers, the lagging-strand polymerase restarts at short intervals and produces Okazaki fragments. At least in prokaryotic systems, this directionality problem is solved by the formation of a loop in the lagging strand of the replication fork to reorient the lagging-strand DNA polymerase so that it advances in parallel with the leading-strand polymerase. The replication loop grows and shrinks during each cycle of Okazaki fragment synthesis. Here we use single-molecule techniques to visualize, in real time, the formation and release of replication loops by individual replisomes of bacteriophage T7 supporting coordinated DNA replication. Analysis of the distributions of loop sizes and lag times between loops reveals that initiation of primer synthesis and the completion of an Okazaki fragment each serve as a trigger for loop release. The presence of two triggers may represent a fail-safe mechanism ensuring the timely reset of the replisome after the synthesis of every Okazaki fragment.