Syndesomes for enhanced wound healing and therapeutic angiogenesis in a diabetic diseased state

Peripheral vascular disease (PVD) affects more than 202 million people globally and about 20% of the population above 65 years of age in the United States alone. Type-2 diabetes afflicts around 347 million people worldwide and leads to the death of 4.6 million people. The rising prevalence of strong risk factors like smoking, hypertension, hypercholesterolemia, and obesity indicate that the affected population will continue to grow. Currently no long-term therapies exist in clinical practice for peripheral ischemia and non-healing chronic ulcers, both of which are common clinical consequences of PVD and type-2 diabetes. Current clinical treatments including exercise therapy, pharmaco- therapy, and surgical intervention can provide only relatively short-term relief from progressive vascular disease. Some attractive therapeutic strategies are to use growth factors, cytokines, viral delivery of growth factor genes, or the implantation of stem cells to revascularize ischemic tissue and heal chronic wounds. While these emerging therapies have been successfully applied in healthy animal models, they have achieved only limited success in humans with long-term disease. Thus, the overall goal of this thesis is to understand the reasons behind the failure of the clinical trials using growth factor therapy and to engineer therapeutics to circumvent the problems. We observed a dramatic reduction in the protein levels of growth factor co- receptors, including syndecan-4, in the diabetic mouse model. We speculated that since co-receptors are critical for growth factor signaling cascade, this reduction in expression might lead to inefficient growth factor signaling. Our hypothesis was confirmed in the diseased ob/ob mice where we observed significant resistance to angiogenesis via growth factor therapy. Co-delivery of syndecan-4 along with fibroblast growth factor-2 (FGF-2) in an optimized liposomal formulation (syndesome) drastically improved the body’s responsiveness to FGF-2. Treatment with syndesomes also enhanced revascularization in ischemic hind limbs and increased wound healing in full thickness cutaneous wounds in the diseased mouse model. The studies performed and described here are the first attempt, to our knowledge, for an effective understanding of the mechanisms involved in metabolic disorder in humans due to long-term disease and to explore steps for overcoming the associated clinical problems.Biomedical Engineerin

Higher Order Differential Analysis of NORX

In this paper, we analyse the higher order differential properties of NORX, an AEAD scheme submitted to CAESAR competition. NORX is a sponge based construction. Previous efforts, by the designers themselves, have focused on the first order differentials and rotational properties for a small number of steps of the NORX core permutation, which turn out to have quite low biases when extended to the full permutation. In our work, the higher order differential properties are identified that allow to come up with practical distinguishers of the 4-round full permutation for NORX64 and half round less than the full permutation (i.e., 3.5-round) for NORX32. These distinguishers are similar to zero-sum distinguishers but are probabilistic in nature rather than deterministic, and are of order as low as four. The distinguishers have very low complexities, and are significantly more efficient than the generic generalized birthday attack for the same configurations of zero-sums. While these distinguishers identify sharper non-randomness than what the designers identified, our results do not lend themselves for cryptanalysis of full-round NORX encryption or authentication

Ten simple rules for providing a meaningful research experience to high school students

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Quantum noise limited microwave amplification using a graphene Josephson junction

Josephson junctions (JJ) and their tunable properties, including their nonlinearities, form the core of superconducting circuit quantum electrodynamics (cQED). In quantum circuits, low-noise amplification of feeble microwave signals is essential and the Josephson parametric amplifiers (JPA) are the widely used devices. The existing JPAs are based on Al-AlOx-Al tunnel junctions realized in a superconducting quantum interference device geometry, where magnetic flux is the knob for tuning the frequency. Recent experimental realizations of 2D van der Waals JJs provide an opportunity to implement various cQED devices with the added advantage of tuning the junction properties and the operating point using a gate potential. While other components of a possible 2D van der Waals cQED architecture have been demonstrated -- quantum noise limited amplifier, an essential component, has not been realized. Here we implement a quantum noise limited JPA, using a graphene JJ, that has linear resonance gate tunability of 3.5 GHz. We report 24 dB amplification with 10 MHz bandwidth and -130 dBm saturation power; performance on par with the best single-junction JPAs. Importantly, our gate tunable JPA works in the quantum-limited noise regime which makes it an attractive option for highly sensitive signal processing. Our work has implications for novel bolometers -- the low heat capacity of graphene together with JJ nonlinearity can result in an extremely sensitive microwave bolometer embedded inside a quantum noise-limited amplifier. In general, our work will open up exploration of scalable device architecture of 2D van der Waals materials by integrating a sensor with the quantum amplifier.Comment: 15 pages, 4 figures, and supplementary informatio

An engineered gastrointestinally stable microbial leucine decarboxylase for potential treatment of maple syrup urine disease

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Biomaterials and Nanotherapeutics for Enhancing Skin Wound Healing

Wound healing is an intricate process that requires complex coordination between many cells and an appropriate extracellular microenvironment. Chronic wounds often suffer from high protease activity, persistent infection, excess inflammation, and hypoxia. While there has been intense investigation to find new methods to improve cutaneous wound care; the management of chronic wounds, burns, and skin wound infection remain challenging clinical problems. Ideally, advanced wound dressings can provide enhanced healing and bridge the gaps in the healing processes that prevent chronic wounds from healing. These technologies have great potential for improving outcomes in patients with poorly healing wounds but face significant barriers in addressing the heterogeneity and clinical complexity of chronic or severe wounds. Active wound dressings aim to enhance the natural healing process and work to counter many aspects that plague poorly healing wounds including excessive inflammation, ischemia, scarring and wound infection. This review paper discusses recent advances in the development of biomaterials and nanoparticle therapeutics to enhance wound healing. In particular, this review focuses on the novel cutaneous wound treatments that have undergone significant preclinical development or currently used in clinical practice

Syndecan-4 proteoliposomes for enhanced cutaneous wound healing and minimized inflammatory immune response

Disclosed herein are compositions and articles for wound healing that contain proteovesicles, comprising a syndecan polypeptide embedded in a lipid vesicle, and a PDGF polypeptide. Also disclosed is the use of these compositions to enhance wound healing.Board of Regents, University of Texas Syste

Distribution and homing of tree snail Rachis bengalensis Lamarck (Gastropoda) on a new host plant

Volume: 95Start Page: 142End Page: 14

Overcoming Disease-Induced Growth Factor Resistance in Therapeutic Angiogenesis Using Recombinant Co-Receptors Delivered by a Liposomal System

Current treatment options for ischemia include percutaneous interventions, surgical bypass or pharmacological interventions aimed at slowing the progression of vascular disease. Unfortunately, while each of these treatment modalities provides some benefit for patients in the short-term, many patients have resistant or recurrent disease that is poorly managed by these therapies. A highly appealing strategy for treating ischemic disease is to stimulate the revascularization of the tissue to restore blood flow. While many techniques have been explored in this regard, clinically effective angiogenic therapies remain elusive. Here, we hypothesized that the presence of co-morbid disease states inherently alters the ability of the body to respond to angiogenic therapies. Using a mouse model of diabetes and obesity, we examined alterations in the major components for the signaling pathways for FGF-2, VEGF-A and PDGF under normal and high fat dietary conditions. In skeletal muscle, a high fat diet increased levels of growth factor receptors and co-receptors including syndecan-1, syndecan-4 and PDGFR-alpha in wild-type mice. These increases did not occur in Ob/Ob mice on a high fat diet and there was a significant decrease in protein levels for neuropilin-1 and heparanase in these mice. With the aim of increasing growth factor effectiveness in the context of disease, we examined whether local treatment with alginate gel-delivered FGF-2 and syndecan-4 proteoliposomes could overcome the growth factor resistance in these mice. This treatment enhanced the formation of new blood vessels in Ob/Ob mice by 6 fold in comparison to FGF-2 delivered alone. Our studies support that disease states cause a profound shift in growth factor signaling pathways and that co-receptor-based therapies have potential to overcome growth factor resistance in the context of disease.Biomedical Engineerin