Immunogenicity of unprocessed and photooxidized bovine and human osteochondral grafts in collagen-sensitive mice

BACKGROUND: Autologous and allogeneic osteochondral grafts have been used to repair damaged or diseased cartilage. There are drawbacks to both of these methods, however. Another possible source for osteochondral grafting is photooxidized xenograft scaffolds. The purpose of this study was to evaluate the adaptive immune response to unprocessed and photooxidized xenogeneic osteochondral grafts in a collagen-sensitive mouse model. METHODS: Unprocessed and photooxidized bovine and human osteochondral grafts were used. The grafts were implanted subcutaneously in collagen-sensitive DBA/1LacJ mice for four or twelve weeks. ELISPOT assays were conducted with spleen cells to evaluate the number of collagen-specific T cells that produce IL-2, IL-4, IL-5 or IFN-γ. Serum was collected and ELISA assays were performed to determine the titers of collagen-specific and total IgG, IgG1, IgG2a, or IgM antibodies. Histology was conducted on the retrieved osteochondral grafts. RESULTS: Results indicated that, with respect to adaptive T cell immunity, the photooxidized bovine grafts, unprocessed human grafts and photooxidized human grafts did not induce a significant response to collagen. The unprocessed bovine grafts, however, were slightly more immunogenic, inducing a weak immune response. With respect to antibody production, the bovine grafts were less immunogenic than the human grafts. Bovine collagen-specific IgG antibodies were not induced by these grafts, but production of IgM after twelve weeks was observed with both the unprocessed and photooxidized bovine grafts. In contrast, photooxidized human osteochondral grafts induced IgG1 and IgG2a antibodies, while the unprocessed human grafts did not. Pre-existing human collagen-specific IgM antibodies were present in all mice, including sham-operated negative controls that did not receive an implant. Histological analysis revealed some degree of fibrous encapsulation and inflammatory infiltrations in both bovine and human implants, whether unprocessed or photooxidized. CONCLUSION: Both bovine and human cartilage grafts showed weak, but clear immunogenicity in the DBA/1LacJ mice, indicating that immunogenic collagen was still contained in the grafts, even after cleaning and photooxidation. The process of photooxidation is still important in osteochondral grafting, since it stabilizes the surface of the cartilage by cross-linking the collagen fibers, and allows for immediate load bearing and joint resurfacing

The vimentin cytoskeleton: when polymer physics meets cell biology

The proper functions of tissues depend on the ability of cells to withstand stress and maintain shape. Central to this process is the cytoskeleton, comprised of three polymeric networks: F-actin, microtubules, and intermediate filaments (IFs). IF proteins are among the most abundant cytoskeletal proteins in cells; yet they remain some of the least understood. Their structure and function deviate from those of their cytoskeletal partners, F-actin and microtubules. IF networks show a unique combination of extensibility, flexibility and toughness that confers mechanical resilience to the cell. Vimentin is an IF protein expressed in mesenchymal cells. This review highlights exciting new results on the physical biology of vimentin intermediate filaments and their role in allowing whole cells and tissues to cope with stress

Probability for Primordial Black Holes Pair in 1/R Gravity

The probability for quantum creation of an inflationary universe with a pair of black holes in 1/R - gravitational theory has been studied. Considering a gravitational action which includes a cosmological constant ($\Lambda$) in addition to $\delta R^{- 1}$ term, the probability has been evaluated in a semiclassical approximation with Hartle-Hawking boundary condition. We obtain instanton solutions determined by the parameters $\delta$ and $\Lambda$ satisfying the constraint $\delta \leq \frac{4 \Lambda^{2}}{3}$. However, we note that two different classes of instanton solutions exists in the region $0 < \delta < \frac{4 \Lambda^{2}}{3}$. The probabilities of creation of such configurations are evaluated. It is found that the probability of creation of a universe with a pair of black holes is strongly suppressed with a positive cosmological constant except in one case when $0 < \delta < \Lambda^{2}$. It is also found that gravitational instanton solution is permitted even with $\Lambda = 0$ but one has to consider $\delta < 0$. However, in the later case a universe with a pair of black holes is less probable.Comment: 15 pages, no figure. submitted to Phys. Rev.

Plasma insulin-like factor 3 (INSL3) in male patients with osteoporosis and Klinefelter’s syndrome

Insulin-like factor 3 (INSL3) is a peptide hormone produced in leydig cells of the testes. Its role in the adult male is unknown but INSL3 and its receptor RXFP2 have been linked to bone cell differentiation. It is speculated that low levels of INSL3 could be responsible for low bone mineral density in patients with primary osteoporosis and Klinefelter’s Syndrome. The aim of this study was to assess plasma INSL3 in patients with osteoporosis and Klinefelter’s Syndrome compared to healthy males. Fourteen healthy males, 21 males with osteoporosis (4 primary and 17 secondary) and 4 patients with Klinefelter’s Syndrome were studied. Plasma INSL3, testosterone, LH, FSH and Sex hormone-binding globulin were evaluated. Plasma INSL3 concentrations were similar in osteoporosis patients compared to healthy controls (0.72 vs. 0.69 ng/mL, p=0.26). INSL3 was significantly higher in patients with primary osteoporosis (n=4) compared to age-matched healthy controls (n=8) (0.845 vs. 0.665 ng/mL, p=0.021). INSL3 levels in Klinefelter’s Syndrome patients were significantly lower compared to healthy controls (0.39 vs. 0.69 ng/mL, p=0.01). Plasma INSL3 levels were lower in Klinefelter’s Syndrome reflecting testicular failure. INSL3 levels were not lower in men with osteoporosis. The relationship between INSL3, its receptor and bone metabolism requires further study

Spin half fermions with mass dimension one: theory, phenomenology, and dark matter

We provide the first details on the unexpected theoretical discovery of a spin-one-half matter field with mass dimension one. It is based upon a complete set of dual-helicity eigenspinors of the charge conjugation operator. Due to its unusual properties with respect to charge conjugation and parity, it belongs to a non-standard Wigner class. Consequently, the theory exhibits non-locality with (CPT)^2 = - I. We briefly discuss its relevance to the cosmological `horizon problem'. Because the introduced fermionic field is endowed with mass dimension one, it can carry a quartic self-interaction. Its dominant interaction with known forms of matter is via Higgs, and with gravity. This aspect leads us to contemplate the new fermion as a prime dark matter candidate. Taking this suggestion seriously we study a supernova-like explosion of a galactic-mass dark matter cloud to set limits on the mass of the new particle and present a calculation on relic abundance to constrain the relevant cross-section. The analysis favours light mass (roughly 20 MeV) and relevant cross-section of about 2 pb. Similarities and differences with the WIMP and mirror matter proposals for dark matter are enumerated. In a critique of the theory we bare a hint on non-commutative aspects of spacetime, and energy-momentum space.Comment: 78 pages [Changes: referee-suggested improvements, additional important references, and better readability

Laser-plasma interactions in long-scale-length plasmas under direct-drive National Ignition Facility conditions

Laser-plasma interaction experiments have been carried out on the OMEGA laser system [T. R. Boehly et al., Opt. Commun. 133, 495 (1997)] under plasma conditions representative of the peak of a 1.5 MJ direct-drive laser pulse proposed for the National Ignition Facility (NIF). Plasmas have been formed by exploding 18–20 μm thick CH foils and by irradiating solid CH targets from one side, using up to 20 kJ of laser energy with phase plates installed on all beams. These plasmas and the NIF plasmas are predicted to have electron temperatures of 4 keV and density scale lengths close to 0.75 mm at the peak of the laser pulse. The electron temperature and density of the exploding-foil plasmas have been diagnosed using time-resolved x-ray spectroscopy and stimulated Raman scattering, respectively, and are consistent with predictions of the two-dimensional Eulerian hydrodynamics code SAGE [R. S. Craxton and R. L. McCrory, J. Appl. Phys. 56, 108 (1984)]. When the solid-target or exploding-foil plasmas were irradiated with an f/6f/6 interaction beam at 1.5×1015 W/cm2,1.5×1015W/cm2, well above the NIF f/8f/8 cluster intensity of ∼ 2×1014 W/cm2,∼2×1014W/cm2, stimulated Brillouin backscattering (SBS) was found to be completely inhibited. A conservative upper limit of direct-backscattered SRS was found to be ∼5% from the solid targets. SRS and SBS are thus unlikely to have a significant impact on target performance at the peak of the NIF direct-drive laser pulse. © 1999 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/70094/2/PHPAEN-6-5-2072-1.pd

The generalized second law of thermodynamics of the universe bounded by the event horizon and modified gravity theories

In this paper, we investigate the validity of the generalized second law of thermodynamics of the universe bounded by the event horizon. Here we consider homogeneous and isotropic model of the universe filled with perfect fluid in one case and in another case holographic model of the universe has been considered. In the third case the matter in the universe is taken in the form of non-interacting two fluid system as holographic dark energy and dust. Here we study the above cases in the Modified gravity, f(R) gravity.Comment: 9 page

Magnetic operations: a little fuzzy physics?

We examine the behaviour of charged particles in homogeneous, constant and/or oscillating magnetic fields in the non-relativistic approximation. A special role of the geometric center of the particle trajectory is elucidated. In quantum case it becomes a 'fuzzy point' with non-commuting coordinates, an element of non-commutative geometry which enters into the traditional control problems. We show that its application extends beyond the usually considered time independent magnetic fields of the quantum Hall effect. Some simple cases of magnetic control by oscillating fields lead to the stability maps differing from the traditional Strutt diagram.Comment: 28 pages, 8 figure

Insulin micro-secretion in Type 1 diabetes and related microRNA profiles

The aim of this cross-sectional study was to compare plasma C-peptide presence and levels in people without diabetes (CON) and with Type 1 diabetes and relate C-peptide status to clinical factors. In a subset we evaluated 50 microRNAs (miRs) previously implicated in beta-cell death and associations with clinical status and C-peptide levels. Diabetes age of onset was stratified as adult (≥ 18 y.o) or childhood ( 20 years. Plasma C-peptide was measured by ultrasensitive ELISA. Plasma miRs were quantified using TaqMan probe-primer mix on an OpenArray platform. C-peptide was detectable in 55.3% of (n= 349) people with diabetes, including 64.1% of adults and 34.0% of youth with diabetes, p 20 years) had detectable C-peptide (60%) than in those with shorter diabetes duration (39%, p for trend< 0.05). Nine miRs significantly correlated with detectable C-peptide levels in people with diabetes and 16 miRs correlated with C-peptide levels in CON. Our cross-sectional study results are supportive of (a) greater beta-cell function loss in younger onset Type 1 diabetes; (b) persistent insulin secretion in adult-onset diabetes and possibly regenerative secretion in childhood-onset long diabetes duration; and (c) relationships of C-peptide levels with circulating miRs. Confirmatory clinical studies and related basic science studies are merited

Dark energy cosmology with generalized linear equation of state

Dark energy with the usually used equation of state $p=w\rho$, where $w=const<0$ is hydrodynamically unstable. To overcome this drawback we consider the cosmology of a perfect fluid with a linear equation of state of a more general form $p=\alpha(\rho-\rho_0)$, where the constants $\alpha$ and $\rho_0$ are free parameters. This non-homogeneous linear equation of state provides the description of both hydrodynamically stable ($\alpha>0$) and unstable ($\alpha<0$) fluids. In particular, the considered cosmological model describes the hydrodynamically stable dark (and phantom) energy. The possible types of cosmological scenarios in this model are determined and classified in terms of attractors and unstable points by the using of phase trajectories analysis. For the dark energy case there are possible some distinctive types of cosmological scenarios: (i) the universe with the de Sitter attractor at late times, (ii) the bouncing universe, (iii) the universe with the Big Rip and with the anti-Big Rip. In the framework of a linear equation of state the universe filled with an phantom energy, $w<-1$, may have either the de Sitter attractor or the Big Rip.Comment: 12 pages, 11 figures, typos corrected, references adde