Collagen-mimetic peptide-modifiable hydrogels for articular cartilage regeneration

Regenerative medicine strategies for restoring articular cartilage face significant challenges to recreate the complex and dynamic biochemical and biomechanical functions of native tissues. As an approach to recapitulate the complexity of the extracellular matrix, collagen-mimetic proteins offer a modular template to incorporate bioactive and biodegradable moieties into a single construct. We modified a Streptococcal collagen-like 2 protein with hyaluronic acid (HA) or chondroitin sulfate (CS)-binding peptides and then cross-linked with a matrix metalloproteinase 7 (MMP7)-sensitive peptide to form biodegradable hydrogels. Human mesenchymal stem cells (hMSCs) encapsulated in these hydrogels exhibited improved viability and significantly enhanced chondrogenic differentiation compared to controls that were not functionalized with glycosaminoglycan-binding peptides. Hydrogels functionalized with CS-binding peptides also led to significantly higher MMP7 gene expression and activity while the HA-binding peptides significantly increased chondrogenic differentiation of the hMSCs. Our results highlight the potential of this novel biomaterial to modulate cell-mediated processes and create functional tissue engineered constructs for regenerative medicine applications

Mapping Local Cytosolic Enzymatic Activity in Human Esophageal Mucosa with Porous Silicon Nanoneedles

Porous silicon nanoneedles can map Cathepsin B activity across normal and tumor human esophageal mucosa. Assembling a peptide‐based Cathepsin B cleavable sensor over a large array of nano­needles allows the discrimination of cancer cells from healthy ones in mixed culture. The same sensor applied to tissue can map Cathepsin B activity with high resolution across the tumor margin area of esophageal adenocarcinoma. [Image: see text

Multi-modal hydrogel-based platform to deliver and monitor cardiac progenitor/stem cell engraftment

Retention and survival of transplanted cells are major limitations to the efficacy of regenerative medicine, with short-term paracrine signals being the principal mechanism underlying current cell therapies for heart repair. Consequently, even improvements in short-term durability may have a potential impact on cardiac cell grafting. We have developed a multimodal hydrogel-based platform comprised of a poly(ethylene glycol) network cross-linked with bioactive peptides functionalized with Gd(III) in order to monitor the localization and retention of the hydrogel in vivo by magnetic resonance imaging. In this study, we have tailored the material for cardiac applications through the inclusion of a heparin-binding peptide (HBP) sequence in the cross-linker design and formulated the gel to display mechanical properties resembling those of cardiac tissue. Luciferase-expressing cardiac stem cells (CSC-Luc2) encapsulated within these gels maintained their metabolic activity for up to 14 days in vitro. Encapsulation in the HBP hydrogels improved CSC-Luc2 retention in the mouse myocardium and hind limbs at 3 days by 6.5- and 12- fold, respectively. Thus, this novel heparin-binding based, Gd(III)-tagged hydrogel and CSC-Luc2 platform system demonstrates a tailored, in vivo detectable theranostic cell delivery system that can be implemented to monitor and assess the transplanted material and cell retention

Field evidence for the influence of weathering on rock erodibility and channel form in bedrock rivers

Erosion processes in bedrock-floored rivers shape channel cross-sectional geometry and the broader landscape. However, the influence of weathering on channel slope and geometry is not well understood. Weathering can produce variation in rock erodibility within channel cross-sections. Recent numerical modeling results suggest that weathering may preferentially weaken rock on channel banks relative to the thalweg, strongly influencing channel form. Here, we present the first quantitative field study of differential weathering across channel cross-sections. We hypothesize that average cross-section erosion rate controls the magnitude of this contrast in weathering between the banks and the thalweg. Erosion rate, in turn, is moderated by the extent to which weathering processes increase bedrock erodibility. We test these hypotheses on tributaries to the Potomac River, Virginia, with inferred erosion rates from similar to 0.1m/kyr to \u3e0.8m/kyr, with higher rates in knickpoints spawned by the migratory Great Falls knickzone. We selected nine channel cross-sections on three tributaries spanning the full range of erosion rates, and at multiple flow heights we measured (1) rock compressive strength using a Schmidt hammer, (2) rock surface roughness using a contour gage combined with automated photograph analysis, and (3) crack density (crack length/area) at three cross-sections on one channel. All cross-sections showed significant (

Thermodynamical Metrics and Black Hole Phase Transitions

An important phase transition in black hole thermodynamics is associated with the divergence of the specific heat with fixed charge and angular momenta, yet one can demonstrate that neither Ruppeiner's entropy metric nor Weinhold's energy metric reveals this phase transition. In this paper, we introduce a new thermodynamical metric based on the Hessian matrix of several free energy. We demonstrate, by studying various charged and rotating black holes, that the divergence of the specific heat corresponds to the curvature singularity of this new metric. We further investigate metrics on all thermodynamical potentials generated by Legendre transformations and study correspondences between curvature singularities and phase transition signals. We show in general that for a system with n-pairs of intensive/extensive variables, all thermodynamical potential metrics can be embedded into a flat (n,n)-dimensional space. We also generalize the Ruppeiner metrics and they are all conformal to the metrics constructed from the relevant thermodynamical potentials.Comment: Latex, 25 pages, reference added, typos corrected, English polished and the Hawking-Page phase transition clarified; to appear in JHE

Interleukin-1 polymorphisms associated with increased risk of gastric cancer

Helicobacter pylori infection is associated with a variety of clinical outcomes including gastric cancer and duodenal ulcer disease. The reasons for this variation are not clear, but the gastric physiological response is influenced by the severity and anatomical distribution of gastritis induced by H. pylori. Thus, individuals with gastritis predominantly localized to the antrum retain normal (or even high) acid secretion, whereas individuals with extensive corpus gastritis develop hypochlorhydria and gastric atrophy, which are presumptive precursors of gastric cancer. Here we report that interleukin-1 gene cluster polymorphisms suspected of enhancing production of interleukin-1-beta are associated with an increased risk of both hypochlorhydria induced by H. pylori and gastric cancer. Two of these polymorphism are in near-complete linkage disequilibrium and one is a TATA-box polymorphism that markedly affects DNA-protein interactions in vitro. The association with disease may be explained by the biological properties of interleukin-1-beta, which is an important pro-inflammatory cytokine and a powerful inhibitor of gastric acid secretion. Host genetic factors that affect interleukin-1-beta may determine why some individuals infected with H. pylori develop gastric cancer while others do no

Two-Way Minimization: A Novel Treatment Allocation Method for Small Trials

Randomization is a hallmark of clinical trials. If a trial entails very few subjects and has many prognostic factors (or many factor levels) to be balanced, minimization is a more efficient method to achieve balance than a simple randomization. We propose a novel minimization method, the ‘two-way minimization’. The method separately calculates the ‘imbalance in the total numbers of subjects’ and the ‘imbalance in the distributions of prognostic factors’. And then to allocate a subject, it chooses—by probability—to minimize either one of these two aspects of imbalances. As such, it is a method that is both treatment-adaptive and covariate-adaptive. We perform Monte-Carlo simulations to examine its statistical properties. The two-way minimization (with proper regression adjustment of the force-balanced prognostic factors) has the correct type I error rates. It also produces point estimates that are unbiased and variance estimates that are accurate. When there are important prognostic factors to be balanced in the study, the method achieves the highest power and the smallest variance among randomization methods that are resistant to selection bias. The allocation can be done in real time and the subsequent data analysis is straightforward. The two-way minimization is recommended to balance prognostic factors in small trials

Operational approach to open dynamics and quantifying initial correlations

A central aim of physics is to describe the dynamics of physical systems. Schrodinger's equation does this for isolated quantum systems. Describing the time evolution of a quantum system that interacts with its environment, in its most general form, has proved to be difficult because the dynamics is dependent on the state of the environment and the correlations with it. For discrete processes, such as quantum gates or chemical reactions, quantum process tomography provides the complete description of the dynamics, provided that the initial states of the system and the environment are independent of each other. However, many physical systems are correlated with the environment at the beginning of the experiment. Here, we give a prescription of quantum process tomography that yields the complete description of the dynamics of the system even when the initial correlations are present. Surprisingly, our method also gives quantitative expressions for the initial correlation.Comment: Completely re-written for clarity of presentation. 15 pages and 2 figure

Optogenetics and deep brain stimulation neurotechnologies

Brain neural network is composed of densely packed, intricately wired neurons whose activity patterns ultimately give rise to every behavior, thought, or emotion that we experience. Over the past decade, a novel neurotechnique, optogenetics that combines light and genetic methods to control or monitor neural activity patterns, has proven to be revolutionary in understanding the functional role of specific neural circuits. We here briefly describe recent advance in optogenetics and compare optogenetics with deep brain stimulation technology that holds the promise for treating many neurological and psychiatric disorders

Plasmonic chirality imprinting on nucleobase-displaying supramolecular nanohelices by metal-nucleobase recognition

Supramolecular self-assembly is an important process that enables the conception of complex structures mimicking biological motifs. Herein, we constructed helical fibrils through chiral self-assembly of nucleobase–peptide conjugates (NPCs), where achiral nucleobases are helically displayed on the surface of fibrils, comparable to polymerized nucleic acids. Selective binding between DNA and the NPC fibrils was observed with fluorescence polarization. Taking advantage of metal–nucleobase recognition, we highlight the possibility of deposition/assembly of plasmonic nanoparticles onto the fibrillar constructs. In this approach, the supramolecular chirality of NPCs can be adaptively imparted to metallic nanoparticles, covering them to generate structures with plasmonic chirality that exhibit significantly improved colloidal stability. The self-assembly of rationally designed NPCs into nanohelices is a promising way to engineer complex, optically diverse nucleobase-derived nanomaterials