Increased CD47 and MHC Class I Inhibitory Signals Expression in Senescent CD1 Primary Mouse Lung Fibroblasts

Cellular senescence is more than a proliferative arrest in response to various stimuli. Senescent cells (SC) participate in several physiological processes, and their adequate removal is essential to maintain tissue and organism homeostasis. However, SC accumulation in aging and age-related diseases alters the tissue microenvironment leading to deterioration. The immune system clears the SC, but the specific scenarios and mechanisms related to recognizing and eliminating them are unknown. Hence, we aimed to evaluate the existence of three regulatory signals of phagocytic function, CD47, major histocompatibility complex class I (MHC-I), and calreticulin, present in the membrane of SC. Therefore, primary fibroblasts were isolated from CD1 female mice lungs, and stress-induced premature senescence (SIPS) was induced with hydrogen peroxide. Replicative senescence (RS) was used as a second senescent model. Our results revealed a considerable increment of CD47 and MHC-I in RS and SIPS fibroblasts. At the same time, no significant changes were found in calreticulin, suggesting that those signals might be associated with evading immune system recognition and thus averting senescent cells clearance.     

d-Hole localization and the suppression of superconductivity in YBa2(Cu1-xZnx)3O7?y

The temperature and Zn concentration dependence of the electrical resistivity, specific heat, magnetic susceptibility, and electron paramagnetic resonance (EPR) spectra of YBa₂(Cu_1–x Zn _x )₃O_7–y withy0.1 has been measured forx0.16. In addition, the temperature and field dependence of the magnetization has been measured for 2<T<300K and 0<H<9.0T, along with the temperature and quasihydrostatic pressure dependence of the electrical resistivity for selected samples for 0<P<13 GPa. The substitution of Zn for Cu in YBa₂Cu₃O_7–y causes a rapid and nearly linear depression of the superconducting transition temperature,T _c , withT _c going to 0 K forx 0.10. YBa₂(Cu_1–x Zn _x )₃O_7–y retains the YBa₂Cu₃O_7-y orthorhombic structure forx0.16 for both the superconducting and nonsuperconducting samples. Initially, the unit cell volume increases nearly linearly with Zn content; however, an abrupt change occurs in the vicinityx=0.8–0.10. Forx<0.10, the temperature dependence of the electrical resistivity,(T), is metallic-like (d/dT>0) and increases gradually with increasing Zn content. However, forx 0.10,(T) becomes semiconductor-like, with a very rapid increase of the resistivity with increasingx. The electrical resistivity, magnetic susceptibility, EPR spectra, and specific heat all indicate that thed-holes associated with the Cu ions become localized in the nonsuperconducting phase,x>-0.10.     

Osteogenic Differentiation of Human Adipose-Derived Stem Cells Seeded on a Biomimetic Spongiosa-like Scaffold: Bone Morphogenetic Protein-2 Delivery by Overexpressing Fascia

Human adipose-derived stem cells (hADSCs) have the capacity for osteogenic differentiation and, in combination with suitable biomaterials and growth factors, the regeneration of bone defects. In order to differentiate hADSCs into the osteogenic lineage, bone morphogenetic proteins (BMPs) have been proven to be highly effective, especially when expressed locally by route of gene transfer, providing a constant stimulus over an extended period of time. However, the creation of genetically modified hADSCs is laborious and time-consuming, which hinders clinical translation of the approach. Instead, expedited single-surgery gene therapy strategies must be developed. Therefore, in an in vitro experiment, we evaluated a novel growth factor delivery system, comprising adenoviral BMP-2 transduced fascia tissue in terms of BMP-2 release kinetics and osteogenic effects, on hADSCs seeded on an innovative biomimetic spongiosa-like scaffold. As compared to direct BMP-2 transduction of hADSCs or addition of recombinant BMP-2, overexpressing fascia provided a more uniform, constant level of BMP-2 over 30 days. Despite considerably higher BMP-2 peak levels in the comparison groups, delivery by overexpressing fascia led to a strong osteogenic response of hADSCs. The use of BMP-2 transduced fascia in combination with hADSCs may evolve into an expedited single-surgery gene transfer approach to bone repair.     

Effect of merging levels of locomotion scores for dairy cows on intra- and interrater reliability and agreement

Locomotion scores are used for lameness detection in dairy cows. In research, locomotion scores with 5 levels are used most often. Analysis of scores, however, is done after transformation of the original 5-level scale into a 4-, 3-, or 2-level scale to improve reliability and agreement. The objective of this study was to evaluate different ways of merging levels to optimize resolution, reliability, and agreement of locomotion scores for dairy cows. Locomotion scoring was done by using a 5-level scale and 10 experienced raters in 2 different scoring sessions from videos from 58 cows. Intra- and interrater reliability and agreement were calculated as weighted kappa coefficient (κw) and percentage of agreement (PA), respectively. Overall intra- and interrater reliability and agreement and specific intra- and interrater agreement were determined for the 5-level scale and after transformation into 4-, 3-, and 2-level scales by merging different combinations of adjacent levels. Intrarater reliability (κw) ranged from 0.63 to 0.86, whereas intrarater agreement (PA) ranged from 60.3 to 82.8% for the 5-level scale. Interrater κw = 0.28 to 0.84 and interrater PA = 22.6 to 81.8% for the 5-level scale. The specific intrarater agreement was 76.4% for locomotion level 1, 68.5% for level 2, 65% for level 3, 77.2% for level 4, and 80% for level 5. Specific interrater agreement was 64.7% for locomotion level 1, 57.5% for level 2, 50.8% for level 3, 60% for level 4, and 45.2% for level 5. Specific intra- and interrater agreement suggested that levels 2 and 3 were more difficult to score consistently compared with other levels in the 5-level scale. The acceptance threshold for overall intra- and interrater reliability (κw and κ ≥0.6) and agreement (PA ≥75%) and specific intra- and interrater agreement (≥75% for all levels within locomotion score) was exceeded only for the 2-level scale when the 5 levels were merged as (12)(345) or (123)(45). In conclusion, when locomotion scoring is performed by experienced raters without further training together, the lowest specific intra- and interrater agreement was obtained in levels 2 and 3 of the 5-level scale. Acceptance thresholds for overall intra- and interrater reliability and agreement and specific intra- and interrater agreement were exceeded only in the 2-level scale.     

Re-evaluating genetic algorithm performance under coordinate rotation of benchmark functions. A survey of some theoretical and practical aspects of genetic algorithms

In recent years, genetic algorithms (GAs) have become increasingly robust and easy to use. Current knowledge and many successful experiments suggest that the application of GAs is not limited to easy-to-optimize unimodal functions. Several results and GA theory give the impression that GAs easily escape from millions of local optima and reliably converge to a single global optimum. The theoretical analysis presented in this paper shows that most of the widely-used test functions have n independent parameters and that, when optimizing such functions, many GAs scale with an O(n ln n) complexity. Furthermore, it is shown that the current design of GAs and its parameter settings are optimal with respect to independent parameters. Both analysis and results show that a rotation of the coordinate system causes a severe performance loss to GAs that use a small mutation rate. In case of a rotation, the GA's complexity can increase up to O(nn) = O(exp(n ln n)). Future work should find new GA designs that solve this performance loss. As long as these problems have not been solved, the application of GAs will be limited to the optimization of easy-to-optimize functions.     

Efficient linear scaling geometry optimization and transition-state search for direct wavefunction optimization schemes in density functional theory using a plane-wave basis

Two linear scaling schemes for the search of stationary points on the nuclear potential energy surface have been developed and implemented for density functional theory programs using plane waves: a geometry optimizer based on the limited-memory Broyden–Fletcher–Goldfarb–Shanno (L-BFGS) method and a linear scaling method for transition-state search based on the microiterative scheme using the partitioned rational function optimizer (P-RFO) and L-BFGS. These optimizers are written with parallelized execution in mind. It is shown that the electronic wavefunction does not need to be fully optimized in the earlier stages of geometry optimization. The reasons for the robustness and good performance of the proposed schemes are identified. Test calculations are presented that use our implementation in the CPMD code.