Power asymmetry in CMB polarization maps from PLANCK : a local variance analysis

A persistent signal of power asymmetry on opposite hemispheres of CMB sky was seen in full-sky temperature measurements made so far. This asymmetry was seen in microwave sky from WMAP as well as PLANCK satellites, and calls for attention the larger question of \emph{statistical isotropy}, one of the foundational principles of modern cosmology. In this work we present an analysis of polarized CMB maps from PLANCK 2015 full mission data. We apply the local variance estimator on low resolution $E-$mode maps from PLANCK 2015 polarization \texttt{Commander} solution. We find a significant hemispherical power asymmetry in polarization data on large angular scales, at the level of $\sim 2.6-3.9\%$ depending on the galactic mask, and the circular disc radius used for computing local variance maps. However the direction is found to be pointing broadly towards CMB kinetic dipole direction. Precise measurements of CMB polarization in future will shed light on this apparent discrepancy in the anisotropy axis seen in temperature and polarized CMB sky, and likely influence of systematics on our findings.Comment: 21 pages, 10 figures, 3 table

Failure properties and microstructure of healthy and aneurysmatic human thoracic aortas subjected to uniaxial extension with a focus on the media

Current clinical practice for aneurysmatic interventions is often based on the maximum diameter of the vessel and/or on the growth rate, although rupture can occur at any diameter and growth rate, leading to fatality. For 27 medial samples obtained from 12 non-aneurysmatic (control) and 9 aneurysmatic human descending thoracic aortas we examined: the mechanical responses up to rupture using uniaxial extension tests of circumferential and longitudinal specimens; the structure of these tissues using second-harmonic imaging and histology, in particular, the content proportions of collagen, elastic fibers and smooth muscle cells in the media. It was found that the mean failure stresses were higher in the circumferential directions (Control-C 1474 kPa; Aneurysmatic-C 1446 kPa), than in the longitudinal directions (Aneurysmatic-L 735kPa; Control-L 579 kPa). This trend was the opposite to that observed for the mean collagen fiber directions measured from the loading axis (Control-L > Aneurysmatic-L > Aneurysmatic-C > Control-C), thus suggesting that the trend in the failure stress can in part be attributed to the collagen architecture. The difference in the mean values of the out-of-plane dispersion in the radial/longitudinal plane between the control and aneurysmatic groups was significant. The difference in the mean values of the mean fiber angle from the circumferential direction was also significantly different between the two groups. Most specimens showed delamination zones near the ruptured region in addition to ruptured collagen and elastic fibers. This study provides a basis for further studies on the microstructure and the uniaxial failure properties of (aneurysmatic) arterial walls towards realistic modeling and prediction of tissue failure

A Regenerative Cardiac Patch Formed by Spray Painting of Biomaterials onto the Heart

Layering a regenerative polymer scaffold on the surface of the heart, termed as a cardiac patch, has been proven to be effective in preserving cardiac function after myocardial infarction (MI). However, the placement of such a patch on the heart usually needs open-chest surgery, which is traumatic, therefore prevents the translation of this strategy into the clinic. We sought to device a way to apply a cardiac patch by spray painting in situ polymerizable biomaterials onto the heart with a minimally invasive procedure. To prove the concept, we used platelet fibrin gel as the “paint” material in a mouse model of MI. The use of the spraying system allowed for placement of a uniform cardiac patch on the heart in a mini-invasive manner without the need for sutures or glue. The spray treatment promoted cardiac repair and attenuated cardiac dysfunction after MI

Derivation of therapeutic lung spheroid cells from minimally invasive transbronchial pulmonary biopsies

BACKGROUND: Resident stem and progenitor cells have been identified in the lung over the last decade, but isolation and culture of these cells remains a challenge. Thus, although these lung stem and progenitor cells provide an ideal source for stem-cell based therapy, mesenchymal stem cells (MSCs) remain the most popular cell therapy product for the treatment of lung diseases. Surgical lung biopsies can be the tissue source but such procedures carry a high risk of mortality. METHODS: In this study we demonstrate that therapeutic lung cells, termed "lung spheroid cells" (LSCs) can be generated from minimally invasive transbronchial lung biopsies using a three-dimensional culture technique. The cells were then characterized by flow cytometry and immunohistochemistry. Angiogenic potential was tested by in-vitro HUVEC tube formation assay. In-vivo bio- distribution of LSCs was examined in athymic nude mice after intravenous delivery. RESULTS: From one lung biopsy, we are able to derive >50 million LSC cells at Passage 2. These cells were characterized by flow cytometry and immunohistochemistry and were shown to represent a mixture of lung stem cells and supporting cells. When introduced systemically into nude mice, LSCs were retained primarily in the lungs for up to 21 days. CONCLUSION: Here, for the first time, we demonstrated that direct culture and expansion of human lung progenitor cells from pulmonary tissues, acquired through a minimally invasive biopsy, is possible and straightforward with a three-dimensional culture technique. These cells could be utilized in long-term expansion of lung progenitor cells and as part of the development of cell-based therapies for the treatment of lung diseases such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF)

Effects of Matrix Metalloproteinases on the Performance of Platelet Fibrin Gel Spiked With Cardiac Stem Cells in Heart Repair: Effects of MMPs on Cell-Gel in Heart Repair

Stem cells and biomaterials have been studied for therapeutic cardiac repair. Previous studies have shown the beneficial effects of platelet fibrin gel and cardiac stem cells when cotransplanted into rodent hearts with myocardial infarction (MI). We hypothesized that matrix metalloproteinases (MMPs) play an important role in such protection. Thus, the present study is designed to elucidate the effects of MMP inhibition on the therapeutic benefits of intramyocardial injection of platelet fibrin gel spiked with cardiac stem cells (cell-gel) in a rat model of acute MI. In vitro, broad-spectrum MMP inhibitor GM6001 undermines cell spreading and cardiomyocyte contraction. In a syngeneic rat model of myocardial infarction, MMP inhibition blunted the recruitment of endogenous cardiovascular cells into the injected biomaterials, therefore hindering de novo angiogenesis and cardiomyogenesis. Echocardiography and histology 3 weeks after treatment revealed that metalloproteinase inhibition diminished the functional and structural benefits of cell-gel in treating MI. Reduction of host angiogenesis, cardiomyocyte cycling, and MMP-2 activities was evident in animals treated with GM6001. Our findings suggest that MMPs play a critical role in the therapeutic benefits of platelet fibrin gel spiked with cardiac stem cells for treating MI

Therapeutic microparticles functionalized with biomimetic cardiac stem cell membranes and secretome

Stem cell therapy represents a promising strategy in regenerative medicine. However, cells need to be carefully preserved and processed before usage. In addition, cell transplantation carries immunogenicity and/or tumourigenicity risks. Mounting lines of evidence indicate that stem cells exert their beneficial effects mainly through secretion (of regenerative factors) and membrane-based cell–cell interaction with the injured cells. Here, we fabricate a synthetic cell-mimicking microparticle (CMMP) that recapitulates stem cell functions in tissue repair. CMMPs carry similar secreted proteins and membranes as genuine cardiac stem cells do. In a mouse model of myocardial infarction, injection of CMMPs leads to the preservation of viable myocardium and augmentation of cardiac functions similar to cardiac stem cell therapy. CMMPs (derived from human cells) do not stimulate T-cell infiltration in immuno-competent mice. In conclusion, CMMPs act as ‘synthetic stem cells’ which mimic the paracrine and biointerfacing activities of natural stem cells in therapeutic cardiac regeneration

Comparison of a New bioprosthetic Mitral Valve to Other Commercially Available Devices Under Controlled Conditions in a Porcine Mode

BACKGROUND/AIM: To evaluate three mitral bioprostheses (of comparable measured internal diameters) under controlled, stable, hemodynamic and surgical conditions by bench, echocardiographic, computerized tomography and autopsy comparisons pre‐ and postvalve implantation. METHODS: Fifteen similar‐sized Yorkshire pigs underwent preprocedural computerized tomography anatomic screening. Of these, 12 had consistent anatomic features and underwent implantation of a mitral bioprosthesis via thoracotomy on cardiopulmonary bypass (CPB). Four valves from each of three manufacturers were implanted in randomized fashion: 27‐mm Epic, 27‐mm Mosaic, and 25‐mm Mitris bioprostheses. After CPB, epicardial echocardiographic studies were performed to assess hemodynamic function and define any paravalvular leaks, followed by postoperative gated contrast computerized tomography. After euthanasia, animals underwent necropsy for anatomic evaluation. RESULTS: All 12 animals had successful valve implantation with no study deaths. Postoperative echocardiographic trans‐valve gradients varied among bioprosthesis manufacturers. The 25‐mm Mitris (5.1 ± 2.7)/(2.6 ± 1.3 torr) had the lowest peak/mean gradient and the 27‐mm Epic bioprosthesis had the highest (9.2 ± 3.7)/(4.6 ± 1.9 torr). Surgical valve opening area (SOA) varied with the 25‐mm Mitris having the largest SOA (2.4 ± 0.15 cm(2)) followed by the 27‐mm Mosaic (2.04 ± 0.23 cm(2)) and the 27‐mm Epic (1.8 ± 0.27 cm(2)) valve. Bench device orthogonal internal diameter measurements did not match manufacturer device size labeling: 25‐mm Mitris (23 × 23 mm), 27‐mm Mosaic (23 × 22 mm), 27‐mm Epic (21 × 21 mm). CONCLUSIONS: Current advertisement/packaging of commercial surgical mitral valves is not uniform. This study demonstrates marked variations in hemodynamics, valve opening area and anatomic dimensions between similar sized mitral bioprostheses. These data suggest a critical need for standardization and close scientific evaluation of surgical mitral bioprostheses to ensure optimal clinical outcomes

Intravenous Cardiac Stem Cell-Derived Exosomes Ameliorate Cardiac Dysfunction in Doxorubicin Induced Dilated Cardiomyopathy

Despite the efficacy of cardiac stem cells (CSCs) for treatment of cardiomyopathies, there are many limitations to stem cell therapies. CSC-derived exosomes (CSC-XOs) have been shown to be responsible for a large portion of the regenerative effects of CSCs. Using a mouse model of doxorubicin induced dilated cardiomyopathy, we study the effects of systemic delivery of human CSC-XOs in mice. Mice receiving CSC-XOs showed improved heart function via echocardiography, as well as decreased apoptosis and fibrosis. In spite of using immunocompetent mice and human CSC-XOs, mice showed no adverse immune reaction. The use of CSC-XOs holds promise for overcoming the limitations of stem cells and improving cardiac therapies

Intravenous Cardiac Stem Cell-Derived Exosomes Ameliorate Cardiac Dysfunction in Doxorubicin Induced Dilated Cardiomyopathy

Despite the efficacy of cardiac stem cells (CSCs) for treatment of cardiomyopathies, there are many limitations to stem cell therapies. CSC-derived exosomes (CSC-XOs) have been shown to be responsible for a large portion of the regenerative effects of CSCs. Using a mouse model of doxorubicin induced dilated cardiomyopathy, we study the effects of systemic delivery of human CSC-XOs in mice. Mice receiving CSC-XOs showed improved heart function via echocardiography, as well as decreased apoptosis and fibrosis. In spite of using immunocompetent mice and human CSC-XOs, mice showed no adverse immune reaction. The use of CSC-XOs holds promise for overcoming the limitations of stem cells and improving cardiac therapies