SPARC, a 32-kDa matricellular glycoprotein, mediates interactions between cells and their extracellular matrix, and targeted deletion of Sparc results in compromised extracellular matrix in mice. ...Fibronectin matrix provides provisional tissue scaffolding during development and wound healing and is essential for the stabilization of mature extracellular matrix. Herein, we report that SPARC expression does not significantly affect fibronectin-induced cell spreading but enhances fibronectin-induced stress fiber formation and cell-mediated partial unfolding of fibronectin molecules, an essential process in fibronectin matrix assembly. By phage display, we identify integrin-linked kinase as a potential binding partner of SPARC and verify the interaction by co-immunoprecipitation and colocalization in vitro. Cells lacking SPARC exhibit diminished fibronectin-induced integrin-linked kinase activation and integrin-linked kinase-dependent cell-contractile signaling. Furthermore, induced expression of SPARC in SPARC-null fibroblasts restores fibronectin-induced integrin-linked kinase activation, downstream signaling, and fibronectin unfolding. These data further confirm the function of SPARC in extracellular matrix organization and identify a novel mechanism by which SPARC regulates extracellular matrix assembly.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Vitamin D deficiency (VDD) is ubiquitous in the Indian subcontinent. VDD has been shown to impair muscle functions. However, the association of VDD with cardiorespiratory endurance is uncertain. ...Hence, we enrolled and supplemented vitamin D in military recruits with VDD with an aim to evaluate effect of supplementation on cardiorespiratory endurance and muscle strength.
We enrolled 90 military recruits with VDD and randomly allotted them to two groups equally. The group I received cholecalciferol granules 60,000 IU every fortnight for twelve weeks (cases), and the group II was observed as control. Muscle strength and cardiorespiratory endurance was assessed with a battery of tests (standing broad jump, bent arm hang test, 20 m shuttle run) at baseline and repeated at the end of training (nineteen weeks). Blood samples were collected for measurement of serum 25(OH)D and parathyroid hormone.
In Group I and Group II, there was significant increase in 25(OH) D levels (25.8 ± 7.1 and 17.3 ± 3.5 ng/ml, respectively), and in VO2 max (9.8 ± 8.8 and 12.7 ± 8.6 ml/kg/min, respectively) compared with the baseline values. However, no significant change was observed in muscle strength after supplementation. There was no difference between the groups in VO2 max and muscle strength at baseline and at the end of training.
Vitamin D supplementation did not improve muscle strength and cardiorespiratory endurance in military recruits with VDD. A significant rise in 25(OH) D was observed even in those not supplemented with vitamin D.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We present the design, fabrication, and experimental characterization of silicon nitride based medium-index contrast gratings on glass substrate for fluorescence enhancement in the yellow to red ...spectral range with resonances for both incident excitation and fluorescence emission wavelengths under surface normal incidence. A comparison of the design space to realize resonant field enhancement in high-index contrast silicon and medium-index contrast silicon nitride grating structures is presented. The one-dimensional sub-wavelength grating structures studied here are designed with large duty cycle (∼80%) to account for the medium refractive index contrast (Δn ∼ 0.5) between silicon nitride and the glass substrate to ensure that the device operates in the two-mode regime. The resonant enhancement of fluorescence is experimentally verified using rhodamine-B isothiocyanate dye as the fluorophore of interest. A resonant enhancement of 10.8 times is demonstrated in this sample when compared to un-patterned film for transverse electric-transverse magnetic (TE-TM) polarization combination. We have also performed simulation study with plane wave excitation and incoherent dipole array emission to model the resonant excitation and emission processes, respectively. The simulations corroborate well with the best observed experimental results for the doubly resonant fluorescence configuration. Silicon nitride based medium contrast gratings are a promising platform to fabricate scalable structures for resonant enhancement of light-matter interaction with potential applications in high-sensitivity biological fluorescence assays and as a platform for polarization selective interrogation of light emission from nanoscale emitters attached to the grating.
The time-evolution operator obtained from the fractional-time Schrödinger equation (FTSE) is said to be nonunitary since it does not preserve the norm of the vector state in time. As done in the ...time-dependent non-Hermitian quantum formalism, for a traceless non-Hermitian two-level quantum system, we demonstrate that it is possible to map the nonunitary time-evolution operator in a unitary one. It is done by considering a dynamical Hilbert space with a time-dependent metric operator, constructed from a Hermitian time-dependent Dyson map, in respect to which the system evolves in a unitary way, and the standard quantum mechanics interpretation can be made properly. To elucidate our approach, we consider three examples of Hamiltonian operators and their corresponding unitary dynamics obtained from the solutions of FTSE, and the respective Dyson maps.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
C-reactive protein and albumin as predictors of all-cause and cardiovascular mortality in chronic kidney disease.
High C-reactive protein (CRP) and hypoalbuminemia are associated with increased risk ...of mortality in patients with kidney failure. There are limited data evaluating the relationships between CRP, albumin, and outcomes in chronic kidney disease (CKD) stages 3 and 4.
The Modification of Diet in Renal Disease (MDRD) Study was a randomized controlled trial conducted between 1989 and 1993. CRP was measured in frozen samples taken at baseline. Survival status and cause of death, up to December 31, 2000, were obtained from the National Death Index. Multivariable Cox models were used to examine the relationship of CRP stratified into high CRP ≥3.0mg/L (N = 414) versus low CRP<3.0mg/L (N = 283), and serum albumin, with all-cause and cardiovascular mortality.
Median follow-up time was 125 months, all-cause mortality was 20% (N = 138) and cardiovascular mortality was 10% (N = 71). In multivariable analyses adjusting for demographic, cardiovascular and kidney disease factors, both high CRP (HR, 95% CI = 1.56, 1.07-2.29) and serum albumin (HR = 0.94 per 0.1 g/dL increase, 95% CI = 0.89-0.99) were independent predictors of all-cause mortality. High CRP (HR 1.94, 95% CI 1.13-3.31), but not serum albumin (HR 0.94, 95% CI 0.87-1.02), was an independent predictor of cardiovascular mortality.
Both high CRP and low albumin, measured in CKD stages 3 and 4, are independent risk factors for all-cause mortality. High CRP, but not serum albumin, is a risk factor for cardiovascular mortality. These results suggest that high CRP and hypoalbuminemia provide prognostic information independent of each other in CKD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Nonlinear optics is an important area of photonics research for realizing active optical functionalities such as light emission, frequency conversion, and ultrafast optical switching for applications ...in optical communication, material processing, precision measurements, spectroscopic sensing and label-free biological imaging. An emerging topic in nonlinear optics research is to realize high efficiency optical functionalities in ultra-small, sub-wavelength length scale structures by leveraging interesting optical resonances in surface relief metasurfaces. Such artificial surfaces can be engineered to support high quality factor resonances for enhanced nonlinear optical interaction by leveraging interesting physical mechanisms. The aim of this review article is to give an overview of the emerging field of nonlinear optics in dielectric based sub-wavelength periodic structures to realize efficient harmonic generators, wavelength mixers, optical switches etc. Dielectric metasurfaces support the realization of high quality-factor resonances with electric field concentrated either inside or in the vicinity of the dielectric media, while at the same time operate at high optical intensities without damage. The periodic dielectric structures considered here are broadly classified into guided-mode resonant structures and resonant metasurfaces. The basic physical mechanisms behind guided-mode resonances, electromagnetically-induced transparency like resonances and bound-states in continuum resonances in periodic photonic structures are discussed. Various nonlinear optical processes studied in such structures with example implementations are also reviewed. Finally, some future directions of interest in terms of realizing large-area metasurfaces, techniques for enhancing the efficiency of the nonlinear processes, heterogenous integration, and extension to non-conventional wavelength ranges in the ultra-violet and infrared region are discussed.
The integration of two-dimensional (2D) materials with resonant photonic structures is seen as a promising direction for enhancing its nonlinear optical response. The design of such heterogeneous ...resonant structures has often relied on multi-parameter sweeps to determine the optimized dimensions of resonant optical structure that results in good resonance characteristics, often in the absence of the 2D material. Such an approach is computationally intensive and may not necessarily result in efficient generation or collection of nonlinear signals from the designed structure. Here, we report hybrid-genetic optimization (HGA) based design and experimental demonstration of second harmonic generation (SHG) enhancement from Fabry–Perot structures of single and double multilayer gallium selenide (GaSe) flakes with bottom silicon dioxide, and index matched polymethyl methacrylate spacer/encapsulation layers. HGA technique utilized here speeds up the multilayer cavity design by 8.8 and 89-times for the single and double GaSe structures when compared to the full parameter-sweep, with measured SHG enhancement of 128- and 400-times, respectively, when compared to a reference sample composed of GaSe layer of optimized thickness on 300 nm silicon dioxide layer. SHG conversion efficiencies obtained from the HGA structures are 1–2 orders of magnitude higher than previous reports on 2D material integrated resonant metasurfaces or Bragg cavities.
Cerebral ischaemia appears to be an important mechanism of secondary neuronal injury in traumatic brain injury (TBI) and is an important predictor of outcome. To date, the thresholds of cerebral ...blood flow (CBF) and cerebral oxygen utilization (CMRO2) for irreversible tissue damage used in TBI studies have been adopted from experimental and clinical ischaemic stroke studies. Identification of irreversibly damaged tissue in the acute phase following TBI could have considerable therapeutic and prognostic implications. However, it is questionable whether stroke thresholds are applicable to TBI. Therefore, the aim of this study was to determine physiological thresholds for the development of irreversible tissue damage in contusional and pericontusional regions in TBI, and to determine the ability of such thresholds to accurately differentiate irreversibly damaged tissue. This study involved 14 patients with structural abnormalities on late-stage MRI, all of whom had been studied with 15O PET within 72 h of TBI. Lesion regions of interest (ROI) and non-lesion ROIs were constructed on late-stage MRIs and applied to co-registered PET maps of CBF, CMRO2 and oxygen extraction fraction (OEF). From the entire population of voxels in non-lesion ROIs, we determined thresholds for the development of irreversible tissue damage as the lower limit of the 95% confidence interval for CBF, CMRO2 and OEF. To test the ability of a physiological variable to differentiate lesion and non-lesion tissue, we constructed probability curves, demonstrating the ability of a physiological variable to predict lesion and non-lesion outcomes. The lower limits of the 95% confidence interval for CBF, CMRO2 and OEF in non-lesion tissue were 15.0 ml/100 ml/min, 36.7 μmol/100 ml/min and 25.9% respectively. Voxels below these values were significantly more frequent in lesion tissue (all P < 0.005, Mann–Whitney U-test). However, a significant proportion of lesion voxels had values above these thresholds, so that definition of the full extent of irreversible tissue damage would not be possible based upon single physiological thresholds. We conclude that, in TBI, the threshold of CBF below which irreversible tissue damage consistently occurs differs from the classical CBF threshold for stroke (where similar methodology is used to define such thresholds). The CMRO2 threshold is comparable to that reported in the stroke literature. At a voxel-based level, however (and in common with ischaemic stroke), the extent of irreversible tissue damage cannot be accurately predicted by early abnormalities of any single physiological variable.
Coronary artery disease occurs in an accelerated fashion in the donor heart after heart transplantation (TxCAD), but the cause is poorly understood. The risk of developing TxCAD is increased by ...cytomegalovirus (CMV) infection and decreased by use of calcium blockers. Our group observed that prophylactic administration of ganciclovir early after heart transplantation inhibited CMV illness, and we now propose to determine whether this therapy also prevents TxCAD.
One hundred forty-nine consecutive patients (131 men and 18 women aged 48+/-13 years) were randomized to receive either ganciclovir or placebo during the initial 28 days after heart transplantation. Immunosuppression consisted of muromonab-CD3 (OKT-3) prophylaxis and maintenance with cyclosporine, prednisone, and azathioprine. Mean follow-up time was 4.7+/-1.3 years. In a post hoc analysis of this trial designed to assess efficacy of ganciclovir for prevention of CMV disease, we compared the actuarial incidence of TxCAD, defined by annual angiography as the presence of any stenosis. Because calcium blockers have been shown to prevent TxCAD, we analyzed the results by stratifying patients according to use of calcium blockers. TxCAD could not be evaluated in 28 patients because of early death or limited follow-up. Among the evaluable patients, actuarial incidence of TxCAD at follow-up (mean, 4.7 years) in ganciclovir-treated patients (n=62) compared with placebo (n=59) was 43+/-8% versus 60+/-10% (P<0.1). By Cox multivariate analysis, independent predictors of TxCAD were donor age >40 years (relative risk, 2.7; CI, 1.3 to 5.5; P<0.01) and no ganciclovir (relative risk, 2.1; CI, 1.1 to 5.3; P=0.04). Stratification on the basis of calcium blocker use revealed differences in TxCAD incidence when ganciclovir and placebo were compared: no calcium blockers (n=53), 32+/-11% (n=28) for ganciclovir versus 62+/-16% (n=25) for placebo (P<0.03); calcium blockers (n=68), 50+/-14% (n=33) for ganciclovir versus 45+/-12% (n=35) for placebo (P=NS).
TxCAD incidence appears to be lower in patients treated with ganciclovir who are not treated with calcium blockers. Given the limitations imposed by post hoc analysis, a randomized clinical trial is required to address this issue.