Cell and Material‐Specific Phage Display Peptides Increase iPS‐MSC Mediated Bone and Vasculature Formation In Vivo

Biomimetically designed materials matching the chemical and mechanical properties of tissue support higher mesenchymal stem cell (MSC) adhesion. However, directing cell‐specific attachment and ensuring uniform cell distribution within the interior of 3D biomaterials remain key challenges in healing critical sized defects. Previously, a phage display derived MSC‐specific peptide (DPIYALSWSGMA, DPI) was combined with a mineral binding sequence (VTKHLNQISQSY, VTK) to increase the magnitude and specificity of MSC attachment to calcium‐phosphate biomaterials in 2D. This study investigates how DPI‐VTK influences quantity and uniformity of iPS‐MSC mediated bone and vasculature formation in vivo. There is greater bone formation in vivo when iPS‐MSCs are transplanted on bone‐like mineral (BLM) constructs coated with DPI‐VTK compared to VTK (p < 0.002), uncoated BLM (p < 0.037), acellular BLM/DPI‐VTK (p < 0.003), and acellular BLM controls (p < 0.01). This study demonstrates, for the first time, the ability of non‐native phage‐display designed peptides to spatially control uniform cell distribution on 3D scaffolds and increase the magnitude and uniformity of bone and vasculature formation in vivo. Taken together, the study validates phage display as a novel technology platform to engineer non‐native peptides with the ability to drive cell specific attachment on biomaterials, direct bone regeneration, and engineer uniform vasculature in vivo.Non‐native peptides derived from a combinatorial phage display are engineered to increase iPS‐MSC attachment on biomaterials and increase the quantity and uniformity of bone and vasculature formation in vivo. Findings validate phage display as a new technology platform to engineer the interface between selective cell populations and specific biomaterial chemistries.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149285/1/adhm201801356_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149285/2/adhm201801356.pd

Molecular Dynamics Simulations of Weak Detonations

Detonation of a three-dimensional reactive non-isotropic molecular crystal is modeled using molecular dynamics simulations. The detonation process is initiated by an impulse, followed by the creation of a stable fast reactive shock wave. The terminal shock velocity is independent of the initiation conditions. Further analysis shows supersonic propagation decoupled from the dynamics of the decomposed material left behind the shock front. The dependence of the shock velocity on crystal nonlinear compressibility resembles solitary behavior. These properties categorize the phenomena as a weak detonation. The dependence of the detonation wave on microscopic potential parameters was investigated. An increase in detonation velocity with the reaction exothermicity reaching a saturation value is observed. In all other respects the model crystal exhibits typical properties of a molecular crystal.Comment: 38 pages, 20 figures. Submitted to Physical Review

IC-Cut: A Compositional Search Strategy for Dynamic Test Generation

Abstract. We present IC-Cut, short for “Interface-Complexity-based Cut”, a new compositional search strategy for systematically testing large programs. IC-Cut dynamically detects function interfaces that are simple enough to be cost-effective for summarization. IC-Cut then hierarchically decomposes the program into units defined by such functions and their sub-functions in the call graph. These units are tested independently, their test results are recorded as low-complexity function summaries, and the summaries are reused when testing higher-level functions in the call graph, thus limiting overall path explosion. When the decomposed units are tested exhaustively, they constitute verified components of the program. IC-Cut is run dynamically and on-the-fly during the search, typically refining cuts as the search advances. We have implemented this algorithm as a new search strategy in the whitebox fuzzer SAGE, and present detailed experimental results ob-tained when fuzzing the ANI Windows image parser. Our results show that IC-Cut alleviates path explosion while preserving or even increasing code coverage and bug finding, compared to the current generational-search strategy used in SAGE.

A histomorphometric meta-analysis of sinus elevation with various grafting materials

Several grafting materials have been used in sinus augmentation procedures including autogenous bone, demineralized freeze-dried bone (DFDBA), hydroxyapatite, β-tricalcium phosphate (β-TCP), anorganic deproteinized bovine bone and combination of these and others. Up to now a subject of controversy in maxillofacial surgery and dentistry is, what is the most appropriate graft material for sinus floor augmentation

Global well-posedness of the KP-I initial-value problem in the energy space

We prove that the KP-I initial value problem is globally well-posed in the natural energy space of the equation

Proving Memory Safety of the ANI Windows Image Parser Using Compositional Exhaustive Testing

We report in this paper how we proved memory safety of a complex Windows image parser written in low-level C in only three months of work and using only three core tech-niques, namely (1) symbolic execution at the x86 binary level, (2) exhaustive program path enumeration and testing, and (3) user-guided program decomposition and summariza-tion. We also used a new tool, named MicroX, for executing code fragments in isolation using a custom virtual machine designed for testing purposes. As a result of this work, we are able to prove, for the first time, that a Windows image parser is memory safe, i.e., free of any buffer-overflow secu-rity vulnerabilities, modulo the soundness of our tools and several additional assumptions regarding bounding input-dependent loops, fixing a few buffer-overflow bugs, and ex-cluding some code parts that are not memory safe by design. In the process, we also discovered and fixed several limita-tions in our tools, and narrowed the gap between systematic testing and verification. 1

Multimodal neuro-nanotechnology: Challenging the existing paradigm in glioblastoma therapy

Integrating multimodal neuro- and nanotechnology-enabled precision immunotherapies with extant systemic immunotherapies may finally provide a significant breakthrough for combatting glioblastoma (GBM). The potency of this approach lies in its ability to train the immune system to efficiently identify and eradicate cancer cells, thereby creating anti-tumor immune memory while minimizing multi-mechanistic immune suppression. A critical aspect of these therapies is the controlled, spatiotemporal delivery of structurally defined nanotherapeutics into the GBM tumor microenvironment (TME). Architectures such as spherical nucleic acids or poly(beta-amino ester)/dendrimer-based nanoparticles have shown promising results in preclinical models due to their multivalency and abilities to activate antigen-presenting cells and prime antigen-specific T cells. These nanostructures also permit systematic variation to optimize their distribution, TME accumulation, cellular uptake, and overall immunostimulatory effects. Delving deeper into the relationships between nanotherapeutic structures and their performance will accelerate nano-drug development and pave the way for the rapid clinical translation of advanced nanomedicines. In addition, the efficacy of nanotechnology-based immunotherapies may be enhanced when integrated with emerging precision surgical techniques, such as laser interstitial thermal therapy, and when combined with systemic immunotherapies, particularly inhibitors of immune-mediated checkpoints and immunosuppressive adenosine signaling. In this perspective, we highlight the potential of emerging treatment modalities, combining advances in biomedical engineering and neurotechnology development with existing immunotherapies to overcome treatment resistance and transform the management of GBM. We conclude with a call to action for researchers to leverage these technologies and accelerate their translation into the clinic