Developing Regenerative Treatments for Developmental Defects, Injuries, and Diseases Using Extracellular Matrix Collagen-Targeting Peptides.

Collagen is the most widespread extracellular matrix (ECM) protein in the body and is important in maintaining the functionality of organs and tissues. Studies have explored interventions using collagen-targeting tissue engineered techniques, using collagen hybridizing or collagen binding peptides, to target or treat dysregulated or injured collagen in developmental defects, injuries, and diseases. Researchers have used collagen-targeting peptides to deliver growth factors, drugs, and genetic materials, to develop bioactive surfaces, and to detect the distribution and status of collagen. All of these approaches have been used for various regenerative medicine applications, including neovascularization, wound healing, and tissue regeneration. In this review, we describe in depth the collagen-targeting approaches for regenerative therapeutics and compare the benefits of using the different molecules for various present and future applications

Low-complexity Noncoherent Iterative CPM Demodulator for FH Communication

In this paper, we investigate the noncoherent iterative demodulation of coded continuous phase modulation (CPM) in frequency hopped (FH) systems. In this field, one important problem is that the complexity of the optimal demodulator is prohibitive unless the number of symbols per hop duration is very small. To solve this problem, we propose a novel demodulator, which reduces the complexity by applying phase quantization and exploiting the phase rotational invariance property of CPM signals. As shown by computational complexity analysis and numerical results, the proposed demodulator approaches the performance of the optimal demodulator, and provides considerable performance improvement over the existing solutions with the same computational complexity

Positive solutions of two-point boundary value problems of nonlinear fractional differential equation at resonance

This paper is concerned with a kind of nonlinear fractional differential boundary value problem at resonance with Caputo's fractional derivative. Our main approach is the recent Leggett-Williams norm-type theorem for coincidences due to O'Regan and Zima. The most interesting point is the acquisition of positive solutions for fractional differential boundary value problem at resonance. Moreover, an example is constructed to show that our result here is valid

In Utero Transplantation of Placenta-Derived Mesenchymal Stromal Cells for Potential Fetal Treatment of Hemophilia A.

Hemophilia A (HA) is an X-linked recessive disorder caused by mutations in the factor VIII ( FVIII) gene leading to deficient blood coagulation. The current standard of care is frequent infusions of plasma-derived FVIII or recombinant B-domain-deleted FVIII (BDD-FVIII). While this treatment is effective, many patients eventually develop FVIII inhibitors that limit the effectiveness of the infused FVIII. As a monogenic disorder, HA is an ideal target for gene or cell-based therapy. Several studies have investigated allogeneic stem cell therapy targeting in utero or postnatal treatment of HA but have not been successful in completely correcting HA. Autologous in utero transplantation of mesenchymal stem cells is promising for treatment of HA due to the naive immune status of the fetal environment as well as its potential to prevent transplant rejection and long-term FVIII inhibitor formation. HA can be diagnosed by chorionic villus sampling performed during the first trimester (10 to 13 wk) of gestation. In this study, we used an established protocol and isolated placenta-derived mesenchymal stromal cells (PMSCs) from first trimester chorionic villus tissue and transduced them with lentiviral vector encoding the BDD-FVIII gene. We show that gene-modified PMSCs maintain their immunophenotype and multipotency, express, and secrete high levels of active FVIII. PMSCs were then transplanted at embryonic day 14.5 (E14.5) into wild-type fetuses from time-mated pregnant mice. Four days after birth, pups were checked for engraftment, and varying levels of expression of human green fluorescent protein were found in the organs tested. This study shows feasibility of the approach to obtain PMSCs from first trimester chorionic villus tissue, genetically modify them with the FVIII gene, and transplant them in utero for cell-mediated gene therapy of HA. Future studies will involve evaluation of long-term engraftment, phenotypic correction in HA mice, and prevention of FVIII inhibitor development by this approach

Positive solutions for higher-order nonlinear fractional differential equation with integral boundary condition

In this paper, we study a kind of higher-order nonlinear fractional differential equation with integral boundary condition. The fractional differential operator here is the Caputo's fractional derivative. By means of fixed point theorems, the existence and multiplicity results of positive solutions are obtained. Furthermore, some examples given here illustrate that the results are almost sharp

The study of higher-order resonant and non-resonant boundary value problems

The existence of at least one solution to a nonlinear $n^\textrm{th}$ order differential equation $x^{(n)} = f(t,x,x',\ldots,x^{(n-1)}), \ 0 <t<1$, under both non-resonant and resonant boundary conditions, is proved. The methods involve the characterization of the $R_\delta$-set and an application of a new generalization for a multi-valued version of the Miranda Theorem