Substance P and Alpha-Calcitonin Gene-Related Peptide Differentially Affect Human Osteoarthritic and Healthy Chondrocytes

Osteoarthritis (OA) is a degenerative joint disease that not only causes cartilage loss but also structural damage in all joint tissues. Joints are innervated by alpha-calcitonin gene-related peptide (αCGRP) and substance P (SP)-positive sensory nerve fibers. Alteration of sensory joint innervation could be partly responsible for degenerative changes in joints that contribute to the development of OA. Therefore, our aim was to analyze and compare the molecular effects of SP and αCGRP on the metabolism of articular chondrocytes from OA patients and non-OA cartilage donors. We treated the cells with SP or αCGRP and analysed the influence of these neuropeptides on chondrocyte metabolism and modulation of signaling pathways. In chondrocytes from healthy cartilage, SP had minimal effects compared with its effects on OA chondrocytes, where it induced inflammatory mediators, inhibited chondrogenic markers and promoted apoptosis and senescence. Treatment with αCGRP also increased apoptosis and senescence and reduced chondrogenic marker expression in OA chondrocytes, but stimulated an anabolic and protective response in healthy chondrocytes. The catabolic influence of SP and αCGRP might be due to activation of ERK signaling that could be counteracted by an increased cAMP response. We suggest that a switch between the G-subunits of the corresponding receptors after binding their ligands SP or αCGRP plays a central role in mediating the observed effects of sensory neuropeptides on chondrocytes

The chemical composition of globular clusters in the Local Group

We present detailed abundance measurements for 45 globular clusters (GCs) in galaxies in (and, in one case, beyond) the Local Group. The measurements are based on new high-resolution integrated-light spectra of GCs in NGC 185, NGC 205, M31, M33, and NGC 2403, combined with reanalysis of previous observations of GCs in the Fornax dSph, WLM, NGC 147, NGC 6822, and the Milky Way. The GCs cover the range -2.8 < [Fe/H] < -0.1 and we determined abundances for Fe, Na, Mg, Si, Ca, Sc, Ti, Cr, Mn, Ni, Cu, Zn, Zr, Ba, and Eu. Corrections for non local thermodynamic equilibrium effects are included for Na, Mg, Ca, Ti, Mn, Fe, Ni, and Ba. For several of the galaxies, our measurements provide the first quantitative constraints on the detailed composition of their metal-poor stellar populations. Overall, the GCs in different galaxies exhibit remarkably uniform abundance patterns of the alpha-, iron-peak, and neutron-capture elements, with a dispersion of less than 0.1 dex in [alpha/Fe] for the full sample. There is a hint that GCs in dwarf galaxies are slightly less alpha-enhanced (by about 0.04 dex on average) than those in larger galaxies. One GC in M33 (HM33-B) resembles the most metal-rich GCs in the Fornax dSph (Fornax 4) and NGC 6822 (SC7) by having alpha-element abundances closer to scaled-solar values, possibly hinting at an accretion origin. We find that the alpha-element abundances strongly correlate with those of Na, Sc, Ni, and Zn. Several GCs with [Fe/H]<-1.5 are deficient in Mg compared to other alpha-elements. We find no GCs with strongly enhanced r-process abundances as reported for metal-poor stars in some ultra-faint dwarfs and the Magellanic Clouds. The similarity of the abundance patterns for metal-poor GCs in different environments points to similar early enrichment histories and only allow for minor variations in the initial mass function.Comment: 34 pages + 6 appendices. Accepted for publication in Astronomy & Astrophysic

Observational constraints on the origin of the elements. V. Non-LTE abundance ratios of [Ni/Fe] in Galactic stars and enrichment by sub-Chandrasekhar mass SNe

We constrain the role of different SN Ia channels in the chemical enrichment of the Galaxy by studying the abundances of nickel in Galactic stars. We investigate four different SN Ia sub-classes, including the classical single-degenerate near-Chandrasekhar mass SN Ia, the fainter SN Iax systems associated with He accretion from the companion, as well as two sub-Ch mass SN Ia channels. The latter include the double-detonation of a white dwarf accreting helium-rich matter and violent white dwarf mergers. NLTE models of Fe and Ni are used in the abundance analysis. In the GCE models, we include new delay time distributions arising from the different SN Ia channels, as well as recent yields for core-collapse supernovae and AGB stars. The data-model comparison is performed using a Markov chain Monte Carlo framework that allows us to explore the entire parameter space allowed by the diversity of explosion mechanisms and the Galactic SN Ia rate, taking into account the uncertainties of the observed data. We show that NLTE effects have a non-negligible impact on the observed [Ni/Fe] ratios in the Galactic stars. The NLTE corrections to Ni abundances are not large, but strictly positive, lifting the [Ni/Fe] ratios by ~+0.15 dex at [Fe/H] =-2. We find that that the distributions of [Ni/Fe] in LTE and in NLTE are very tight, with a scatter of < 0.1 dex at all metallicities, supporting earlier work. In LTE, most stars have scaled-solar Ni abundances, [Ni/Fe] = 0, with a slight tendency for sub-solar [Ni/Fe] ratios at lower [Fe/H]. In NLTE, however, we find a mild anti-correlation between [Ni/Fe] and metallicity, and a slightly elevated [Ni/Fe] ratios at [Fe/H] < -1.0. The NLTE data can be explained by the GCE models calculated with a substantial, ~ 75%, fraction of sub-Ch SN Ia.Comment: accepted for publication in Astronomy & Astrophysics, abridged version of the abstrac

Silicon solar cell–integrated stress and temperature sensors for photovoltaic modules

We propose silicon solar cell–integrated stress and temperature sensors as a new approach for the stress and temperature measurement in photovoltaic (PV) modules. The solar cell–integrated sensors enable a direct and continuous in situ measurement of mechanical stress and temperature of solar cells within PV modules. In this work, we present a proof of concept for stress and temperature sensors on a silicon solar cell wafer. Both sensors were tested in a conventional PV module setup. For the stress sensor, a sensitivity of (−47.41 ± 0.14)%/GPa has been reached, and for the temperature sensor, a sensitivity of (3.557 ± 0.008) × 10$^{-3}$ K$^{-1}$ has been reached. These sensors can already be used in research for increased measurement accuracy of the temperature and the mechanical stress in PV modules because of the implementation at the precise location of the solar cells within a laminate stack, for process evaluation, in‐situ measurements in reliability tests, and the correlation with real exposure to climates

Специфика взаимодействия лазерного излучения с веществом при лазерной гравировке

Целью работы является выявление закономерности формирования структуры и свойств материала при многократном наложении импульсов лазерного излучения. В ходе работы рассмотрены факторы, влияющие на скорость удаления материала; исследовано влияние параметров лазерного излучения на структуру и свойства материала в зоне воздействия и вблизи ее; определены параметры возникающего пароплазменного факела; определена зависимость амплитуды реактивной отдачи плазменной струи от интенсивности лазерного воздействия. В результате определены области параметров лазерного воздействия наносекундной длительности импульса, при которых наблюдается формирование глубокого проплавления.The aim of the work is to identify patterns of material structure and properties formation with repeated imposition of laser radiation pulses. In the course of the work, factors affecting the rate of material removal are considered; the influence of laser radiation parameters on the structure and properties of the material in the impact zone and near it has been investigated; the parameters of the emerging vapor-plasma flare were determined; the dependence of the amplitude of the reactive recoil of the plasma jet on the intensity of laser irradiation is determined. As a result, the areas of parameters of the laser effect of a nanosecond pulse duration at which the formation of deep melting is observed are determined

Exploring the mechanisms of renoprotection against progressive glomerulosclerosis

In this review, I introduce the strategy developed by our laboratory to explore the mechanisms of renoprotection against progressive glomerulosclerosis leading to renal death. First, I describe the experimental rat model in which disturbances of vascular regeneration and glomerular hemodynamics lead to irreversible glomerulosclerosis. Second, I discuss the possible mechanisms determining the progression of glomerulosclerosis and introduce a new imaging system based on intravital confocal laser scanning microscopy. Third, I provide an in-depth review of the regulatory glomerular hemodynamics at the cellular and molecular levels while focusing on the pivotal role of Ca2+-dependent gap junctional intercellular communication in coordinating the behavior of mesangial cells. Last, I show that local delivery of renoprotective agents, in combination with diagnostic imaging of the renal microvasculature, allows the evaluation of the therapeutic effects of angiotensin II receptor and cyclooxygenase activity local blockade on the progression of glomerulosclerosis, which would otherwise lead to renal death

PDGF-C Induces Maturation of Blood Vessels in a Model of Glioblastoma and Attenuates the Response to Anti-VEGF Treatment

Recent clinical trials of VEGF inhibitors have shown promise in the treatment of recurrent glioblastomas (GBM). However, the survival benefit is usually short-lived as tumors escape anti-VEGF therapies. Here we tested the hypothesis that Platelet Derived Growth Factor-C (PDGF-C), an isoform of the PDGF family, affects GBM progression independent of VEGF pathway and hinders anti-VEGF therapy.We first showed that PDGF-C is present in human GBMs. Then, we overexpressed or downregulated PDGF-C in a human GBM cell line, U87MG, and grew them in cranial windows in nude mice to assess vessel structure and function using intravital microscopy. PDGF-C overexpressing tumors had smaller vessel diameters and lower vascular permeability compared to the parental or siRNA-transfected tumors. Furthermore, vessels in PDGF-C overexpressing tumors had more extensive coverage with NG2 positive perivascular cells and a thicker collagen IV basement membrane than the controls. Treatment with DC101, an anti-VEGFR-2 antibody, induced decreases in vessel density in the parental tumors, but had no effect on the PDGF-C overexpressing tumors.These results suggest that PDGF-C plays an important role in glioma vessel maturation and stabilization, and that it can attenuate the response to anti-VEGF therapy, potentially contributing to escape from vascular normalization