Building on the scientific understanding and technological infrastructure of single-mode fibers, multimode fibers are being explored as a means of adding new degrees of freedom to optical ...technologies such as telecommunications, fiber lasers, imaging, and measurement. Here, starting from a baseline of single-mode nonlinear fiber optics, we introduce the growing topic of multimode nonlinear fiber optics. We demonstrate a new numerical solution method for the system of equations that describes nonlinear multimode propagation, the generalized multimode nonlinear Schrödinger equation. This numerical solver is freely available, implemented in MATLAB and includes a number of multimode fiber analysis tools. It features a significant parallel computing speed-up on modern graphical processing units, translating to orders-of-magnitude speed-up over the conventionally-used split-step Fourier method. We demonstrate its use with several examples in graded- and step-index multimode fibers. Finally, we discuss several key open directions and questions, whose answers could have significant scientific and technological impact.
Antibody (Ab) crosslinking of HLA I molecules on the surface of endothelial cells triggers proliferative and pro‐survival intracellular signaling, which is implicated in the process of chronic ...allograft rejection, also known as transplant vasculopathy (TV). The purpose of this study was to investigate the role of mammalian target of rapamycin (mTOR) in HLA I Ab‐induced signaling cascades. Everolimus provides a tool to establish how the mTOR signal network regulates HLA I–mediated migration, proliferation and survival. We found that everolimus inhibits mTOR complex 1 (mTORC1) by disassociating Raptor from mTOR, thereby preventing class I–induced phosphorylation of mTOR, p70S6K, S6RP and 4E‐BP1, and resultant class I–stimulated cell migration and proliferation. Furthermore, we found that everolimus inhibits class I–mediated mTORC2 activation (1) by disassociating Rictor and Sin1 from mTOR; (2) by preventing class I–stimulated Akt phosphorylation and (3) by preventing class I–mediated ERK phosphorylation. These results suggest that everolimus is more effective than sirolimus at antagonizing both mTORC1 and mTORC2, the latter of which is critical in endothelial cell functional changes leading to TV in solid organ transplantation after HLA I crosslinking. Our findings point to a potential therapeutic effect of everolimus in prevention of chronic Ab‐mediated rejection.
The authors investigate the effects of the mTOR inhibitor everolimus on HLA‐I antibody‐induced endothelial cell signaling, and find that everolimus inhibits HLA‐I antibody‐mediated formation of mTOR complexes, activation of mTORC1‐ and mTORC2‐related signaling networks, and functional changes more potently than sirolimus.
Arginine-rich cell-penetrating peptides do not enter cells by directly passing through a lipid membrane; they instead passively enter vesicles and live cells by inducing membrane multilamellarity and ...fusion. The molecular picture of this penetration mode, which differs qualitatively from the previously proposed direct mechanism, is provided by molecular dynamics simulations. The kinetics of vesicle agglomeration and fusion by an iconic cellpenetrating peptide—nonaarginine—are documented via real-time fluorescence techniques, while the induction of multilamellar phases in vesicles and live cells is demonstrated by a combination of electron and fluorescence microscopies. This concert of experiments and simulations reveals that the identified passive cell penetration mechanism bears analogy to vesicle fusion induced by calcium ions, indicating that the two processes may share a common mechanistic origin.
SRIM – The stopping and range of ions in matter (2010) Ziegler, James F.; Ziegler, M.D.; Biersack, J.P.
Nuclear instruments & methods in physics research. Section B, Beam interactions with materials and atoms,
06/2010, Letnik:
268, Številka:
11
Journal Article
Recenzirano
Odprti dostop
SRIM is a software package concerning the
Stopping and
Range of
Ions in
Matter. Since its introduction in 1985, major upgrades are made about every six years. Currently, more than 700 scientific ...citations are made to SRIM every year. For
SRIM-2010, the following major improvements have been made: (1) About 2800 new experimental stopping powers were added to the database, increasing it to over 28,000 stopping values. (2) Improved corrections were made for the stopping of ions in compounds. (3) New heavy ion stopping calculations have led to significant improvements on SRIM stopping accuracy. (4) A self-contained SRIM module has been included to allow SRIM stopping and range values to be controlled and read by other software applications. (5) Individual interatomic potentials have been included for all ion/atom collisions, and these potentials are now included in the SRIM package. A full catalog of stopping power plots can be downloaded at
www.SRIM.org. Over 500 plots show the accuracy of the stopping and ranges produced by SRIM along with 27,000 experimental data points. References to the citations which reported the experimental data are included.
The behavior of claystone exposed to temperatures up to 1000°C has been investigated experimentally at laboratory scale. Uniaxial and triaxial compressive testing and other measurements of geometric ...and density changes were performed on the specimens after thermal treatment. These experiments showed that compared to untreated specimens, bulk density increases with increasing temperature, while total porosities of those exposed to 200°C and above dramatically increase. Deformation modulus and compressive strength of the specimens exposed to thermal treatment at 800°C and below always increase, but decrease after 1000°C treatment, compared to those exposed at room temperature. In addition, thermal treatment has little influence on the types of stress–strain curves and failure under conditions of confining pressures up to 20MPa and at temperatures up to 1000°C. Micro-crack closure in rocks due to thermal expansion is the main contributor to the increase in strength below 200°C, and baking effects contribute to increase in strength up to 800°C, whereas significant fracturing causes a decrease in strength at 1000°C.
•Bulk density increases with temperature.•The increase in total porosity becomes notable above 200°C.•E and σc at 800°C and below are higher than those at room temperature.•Micro-crack closure and baking effects contribute to the increase in strength.•Fracturing causes a decrease in strength at 1000°C.
The outcomes of many diseases differ between women and men, with women experiencing a higher incidence and more severe pathogenesis of autoimmune and some infectious diseases. It has been suggested ...that this is partially due to activation of plasmacytoid dendritic cells (pDCs), the main producers of interferon (IFN)‐α, in response to toll‐like receptor (TLR)7 stimulation. We investigated the induction of type I IFN (IFN‐I) subtypes upon TLR7 stimulation on isolated pDCs. Our data revealed a sex‐specific differential expression of IFN‐Is, with pDCs from females showing a significantly higher mRNA expression of all 13 IFN‐α subtypes. In addition, pDCs from females had higher levels of IFN‐β mRNA after stimulation, indicating that sex differences in IFN‐I production by pDCs were mediated by a signaling event upstream of the first loop of IFN‐I mRNA transcription. Furthermore, the surface expression levels of the common IFN‐α/β receptor subunit 2 were significantly higher on pDCs from females in comparison to males. These data indicate that higher IFN‐α production is already established at the mRNA level and propose a contribution of higher IFN‐α/β receptor 2 expression on pDCs to the immunological differences in IFN‐I production observed between females and males.
After stimulation via TLR7 (where TLR is toll‐like receptor), plasmacytoid dendritic cells (pDCs) derived from females have higher mRNA expression levels of all IFNA subtypes and IFNB, as well as higher percentages of IFN‐α‐producing pDCs in comparison to males. The common IFN‐α/β receptor is furthermore expressed at higher levels on pDCs from females in comparison to males.
The gut microbiota contributes to host energy metabolism, and altered gut microbiota has been associated with obesity-related metabolic disorders. We previously reported that a probiotic alone or ...together with a prebiotic controls body fat mass in healthy overweight or obese individuals in a randomised, double-blind, placebo controlled clinical study (ClinicalTrials.gov NCT01978691). We now aimed to investigate whether changes in the gut microbiota may be associated with the observed clinical benefits. Faecal and plasma samples were obtained from a protocol compliant subset (n=134) of participants from a larger clinical study where participants were randomised (1:1:1:1) into four groups: (1) placebo, 12 g/d microcrystalline cellulose; (2) Litesse® Ultra™ polydextrose (LU), 12 g/day; (3) Bifidobacterium animalis subsp. lactis 420™ (B420), 10
cfu/d in 12 g microcrystalline cellulose; (4) LU+B420, 1010 cfu/d of B420 in 12 g/d LU for 6 months of intervention. The faecal microbiota composition and metabolites were assessed as exploratory outcomes at baseline, 2, 4, 6 months, and +1 month post-intervention and correlated to obesity-related clinical outcomes. Lactobacillus and Akkermansia were more abundant with B420 at the end of the intervention. LU+B420 increased Akkermansia, Christensenellaceae and Methanobrevibacter, while Paraprevotella was reduced. Christensenellaceae was consistently increased in the LU and LU+B420 groups across the intervention time points, and correlated negatively to waist-hip ratio and energy intake at baseline, and waist-area body fat mass after 6 months treatment with LU+B420. Functional metagenome predictions indicated alterations in pathways related to cellular processes and metabolism. Plasma bile acids glycocholic acid, glycoursodeoxycholic acid, and taurohyodeoxycholic acid and tauroursodeoxycholic acid were reduced in LU+B420 compared to Placebo. Consumption of B420 and its combination with LU resulted in alterations of the gut microbiota and its metabolism, and may support improved gut barrier function and obesity-related markers.
HSC homing, quiescence, and self-renewal depend on the bone marrow HSC niche. A large proportion of solid tumor metastases are bone metastases, known to usurp HSC homing pathways to establish ...footholds in the bone marrow. However, it is not clear whether tumors target the HSC niche during metastasis. Here we have shown in a mouse model of metastasis that human prostate cancer (PCa) cells directly compete with HSCs for occupancy of the mouse HSC niche. Importantly, increasing the niche size promoted metastasis, whereas decreasing the niche size compromised dissemination. Furthermore, disseminated PCa cells could be mobilized out of the niche and back into the circulation using HSC mobilization protocols. Finally, once in the niche, tumor cells reduced HSC numbers by driving their terminal differentiation. These data provide what we believe to be the first evidence that the HSC niche serves as a direct target for PCa during dissemination and plays a central role in bone metastases. Our work may lead to better understanding of the molecular events involved in bone metastases and new therapeutic avenues for an incurable disease.
PDF
