418 research outputs found
Baby Skyrmion chains
Previous results on multi-charged Baby Skyrmion solutions have pointed to a
modular structure, comprised of charge two rings and single charge one
Skyrmions, which combine to form higher charged structures. In this paper we
present numerical evidence which shows an alternative finite chain,
multi-charged global energy minimum Baby Skymion solution. We then proceed from
the infinite plane, to Baby Skyrmions on a cylinder and then a torus, to obtain
the solutions of periodic Baby Skyrmions, of which periodic segments will
correspond to sections of large charge Baby Skyrmions in the plane
BAFF 60-mer, and Differential BAFF 60-mer Dissociating Activities in Human Serum, Cord Blood and Cerebrospinal Fluid.
B cell activation factor of the TNF family (BAFF/BLyS), an essential B cell survival factor of which circulating levels are elevated in several autoimmune disorders, is targeted in the clinic for the treatment of systemic lupus erythematosus (SLE). The soluble form of BAFF can exist as 3-mer, or as 60-mer that results from the ordered assembly of twenty 3-mers and that can be obtained from naturally cleaved membrane-bound BAFF or made as a recombinant protein. However, which forms of soluble BAFF exist and act in humans is unclear. In this study, BAFF 3-mer and 60-mer in biological fluids were characterized for size, activity and response to specific stimulators or inhibitors of BAFF. Human cerebrospinal fluids (CSF) from patients with multiple sclerosis and adult human sera contained exclusively BAFF 3-mer in these assays, also when BAFF concentrations were moderately SLE or highly (BAFFR-deficient individual) increased. Human sera, but not CSF, contained a high molecular weight, saturable activity that dissociated preformed recombinant BAFF 60-mer into 3-mer. This activity was lower in cord blood. Cord blood displayed BAFF levels 10-fold higher than in adults and consistently contained a fair proportion of active high molecular weight BAFF able to dissociate into 3-mer but not endowed with all properties of recombinant BAFF 60-mer. If BAFF 60-mer is produced in humans, it is dissociated, or at least attenuated in the circulation
No interactions between heparin and atacicept, an antagonist of B cell survival cytokines.
The TNF family ligands, B cell activating factor of the TNF family (BAFF, also known as B lymphocyte stimulator, BLyS) and a proliferation-inducing ligand (APRIL), share the transmembrane activator and calcium-modulator and cyclophilin ligand (CAML)-interactor (TACI) as one of their common receptors. Atacicept, a chimeric recombinant TACI/IgG1-Fc fusion protein, inhibits both ligands. TACI and APRIL also bind to proteoglycans and to heparin that is structurally related to proteoglycans. It is unknown whether the portion of TACI contained in atacicept can bind directly to proteoglycans, or indirectly via APRIL, and whether this could interfere with the anti-coagulant properties of heparin.
Binding of atacicept and APRIL to proteoglycan-positive cells was measured by FACS. Activities of heparin and atacicept were measured with activated factor Xa inhibition and cell-based assays. Effects of heparin on circulating atacicept was monitored in mice.
Atacicept did not bind to proteoglycan-positive cells, but when complexed to APRIL could do so indirectly via APRIL. Multimers of atacicept obtained after exposure to cysteine or BAFF 60-mer bound directly to proteoglycans. Atacicept alone, or in complex with APRIL, or in a multimeric form did not interfere with heparin activity in vitro. Conversely, heparin did not influence inhibition of BAFF and APRIL by atacicept and did not change circulating levels of atacicept.
Lack of detectable interference of APRIL-bound or free atacicept on heparin activity makes it unlikely that atacicept at therapeutic doses will interfere with the function of heparin in vivo
Correction to Residual stress relaxation in HFMI amp; 8209;treated fillet welds after single overload peaks
The article Residual stress relaxation in HFMI treated fillet welds after single overload peaks, written by Jan Schubnell, Eva Carl, Majid Farajian, Stefanos Gkatzogiannis, Peter Knödel, Thomas Ummenhofer, Robert Wimpory and Hamdollah Eslami, was originally published Online First without Open Access. After publication in volume 64, issue 6, page 1107 1117 the author decided to opt for Open Choice and to make the article an Open Access publication. Therefore, the copyright of the article has been changed to The Author s 2020 and the article is forthwith distributed under the terms of the Creative Commons Attribution Attribution 4. 0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author s and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http creativecommons.org licenses by 4.
Assessment of the quality of fall detection and management in primary care in the Netherlands based on the ACOVE quality indicators
We determined adherence to nine fall-related ACOVE quality indicators to investigate the quality of management of falls in the elderly population by general practitioners in the Netherlands. Our findings demonstrate overall low adherence to these indicators, possibly indicating insufficiency in the quality of fall management. Most indicators showed a positive association between increased risk for functional decline and adherence, four of which with statistical significance
Substantial reduction of inappropriate tablet splitting with computerised decision support: a prospective intervention study assessing potential benefit and harm
Measurement of differential cross sections for deuteron-proton breakup reaction at 160 MeV
Differential cross sections for deuteron breakup reaction
were measured for a large set of 243 geometrical configurations at the beam
energy of 80 MeV/nucleon. The cross section data are normalized by the
luminosity factor obtained on the basis of simultaneous measurement of elastic
scattering channel and the existing cross section data for this process. The
results are compared to the theoretical calculations modeling nuclear
interaction with and without taking into account the three-nucleon force (3NF)
and Coulomb interaction. In the validated region of the phase space both the
Coulomb force and 3NF play an important role in a good description of the data.
There are also regions, where the improvements of description due to including
3NF are not sufficient
Movement of the human foot in 100 pain free individuals aged 18–45 : implications for understanding normal foot function
Background:
Understanding motion in the normal healthy foot is a prerequisite for understanding the effects of pathology and thereafter setting targets for interventions. Quality foot kinematic data from healthy feet will also assist the development of high quality and research based clinical models of foot biomechanics. To address gaps in the current literature we aimed to describe 3D foot kinematics using a 5 segment foot model in a population of 100 pain free individuals.
Methods:
Kinematics of the leg, calcaneus, midfoot, medial and lateral forefoot and hallux were measured in 100 self reported healthy and pain free individuals during walking. Descriptive statistics were used to characterise foot movements. Contributions from different foot segments to the total motion in each plane were also derived to explore functional roles of different parts of the foot.
Results:
Foot segments demonstrated greatest motion in the sagittal plane, but large ranges of movement in all planes. All foot segments demonstrated movement throughout gait, though least motion was observed between the midfoot and calcaneus. There was inconsistent evidence of movement coupling between joints. There were clear differences in motion data compared to foot segment models reported in the literature.
Conclusions:
The data reveal the foot is a multiarticular structure, movements are complex, show incomplete evidence of coupling, and vary person to person. The data provide a useful reference data set against which future experimental data can be compared and may provide the basis for conceptual models of foot function based on data rather than anecdotal observations
Human PrP90-231-induced cell death is associated with intracellular accumulation of insoluble and protease-resistant macroaggregates and lysosomal dysfunction
To define the mechanisms by which hPrP90-231 induces cell death, we analyzed its interaction with living cells and monitored its intracellular fate. Treatment of SH-SY5Y cells with fluorescein-5-isothiocyanate (FITC)-conjugated hPrP90-231 caused the accumulation of cytosolic aggregates of the prion protein fragment that increased in number and size in a time-dependent manner. The formation of large intracellular hPrP90-231 aggregates correlated with the activation of apoptosis. hPrP90-231 aggregates occurred within lysotracker-positive vesicles and induced the formation of activated cathepsin D (CD), indicating that hPrP90-231 is partitioned into the endosomal–lysosomal system structures, activating the proteolytic machinery. Remarkably, the inhibition of CD activity significantly reduced hPrP-90-231-dependent apoptosis. Internalized hPrP90-231 forms detergent-insoluble and SDS-stable aggregates, displaying partial resistance to proteolysis. By confocal microscopy analysis of lucifer yellow (LY) intracellular partition, we show that hPrP90-231 accumulation induces lysosome destabilization and loss of lysosomal membrane impermeability. In fact, although control cells evidenced a vesicular pattern of LY fluorescence (index of healthy lysosomes), hPrP90-231-treated cells showed diffuse cytosolic fluorescence, indicating LY diffusion through damaged lysosomes. In conclusion, these data indicate that exogenously added hPrP90-231 forms intralysosomal deposits having features of insoluble, protease-resistant aggregates and could trigger a lysosome-mediated apoptosis by inducing lysosome membrane permeabilization, followed by the release of hydrolytic enzymes
- …