2,495 research outputs found
A meta-analysis of structural MRI studies of the brain in systemic lupus erythematosus (SLE)
A comprehensive search of published literature in brain volumetry was conducted in three autoimmune diseases — systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and ulcerative colitis (UC) — with the intention of performing a meta-analysis of published data. Due to the lack of data in RA and UC, the reported meta-analysis was limited to SLE. The MEDLINE database was searched for studies from 1988 to March 2022. A total of 175 papers met the initial inclusion criteria, and 16 were included in a random-effects meta-analysis. The reduction in the number of papers included in the final analysis is primarily due to the lack of overlap in measured and reported brain regions. A significantly lower volume was seen in patients with SLE in the hippocampus, corpus callosum, and total gray matter volume measurements as compared to age- and sex-matched controls. There were not enough studies to perform a meta-analysis for RA and UC; instead, we include a summary of published volumetric studies. The meta-analyses revealed structural brain abnormalities in patients with SLE, suggesting that lower global brain volumes are associated with disease status. This volumetric difference was seen in both the hippocampus and corpus callosum and total gray matter volume measurements. These results indicate both gray and white matter involvements in SLE and suggest there may be both localized and global reductions in brain volume
Structure formation in the presence of relativistic heat conduction: corrections to the Jeans wave number with a stable first order in the gradients formalism
The problem of structure formation in relativistic dissipative fluids was
analyzed in a previous work within Eckart's framework, in which the heat flux
is coupled to the hydrodynamic acceleration, additional to the usual
temperature gradient term. It was shown that in such case, the pathological
behavior of fluctuations leads to the disapperance of the gravitational
instability responsible for structure formation. In the present work the
problem is revisited now using a constitutive equation derived from
relativistic kinetic theory. The new relation, in which the heat flux is not
coupled to the hydrodynamic acceleration, leads to a consistent first order in
the gradients formalism. In this case the gravitational instability remains,
and only relativistic corrections to the Jeans wave number are obtained. In the
calculation here shown the non-relativistc limit is recovered, opposite to what
happens in Eckart's case.Comment: 10 pages, no figure
Endothelial Progenitor Cells and Cardiovascular Events in Patients with Chronic Kidney Disease – a Prospective Follow-Up Study
BACKGROUND: Endothelial progenitor cells (EPCs) mediate vascular repair and regeneration. Their number in peripheral blood is related to cardiovascular events in individuals with normal renal function. METHODS: We evaluated the association between functionally active EPCs (cell culture) and traditional cardiovascular risk factors in 265 patients with chronic kidney disease stage V receiving hemodialysis therapy. Thereafter, we prospectively assessed cardiovascular events, e.g. myocardial infarction, percutaneous transluminal coronary angioplasty (including stenting), aorto-coronary bypass, stroke and angiographically verified stenosis of peripheral arteries, and cardiovascular death in this cohort. RESULTS: In our patients EPCs were related only to age (r=0.154; p=0.01). During a median follow-up period of 36 months 109 (41%) patients experienced a cardiovascular event. In a multiple Cox regression analysis, we identified EPCs (p=0.03) and patient age (p=0.01) as the only independent variables associated with incident cardiovascular events. Moreover, a total of 70 patients died during follow-up, 45 of those due to cardiovascular causes. Log rank test confirmed statistical significance for EPCs concerning incident cardiovascular events (p=0.02). CONCLUSIONS: We found a significant association between the number of functionally active EPCs and cardiovascular events in patients with chronic kidney disease. Thus, defective vascular repair and regeneration may be responsible, at least in part, for the enormous cardiovascular morbidity in this population
Eta Carinae and the Luminous Blue Variables
We evaluate the place of Eta Carinae amongst the class of luminous blue
variables (LBVs) and show that the LBV phenomenon is not restricted to
extremely luminous objects like Eta Car, but extends luminosities as low as
log(L/Lsun) = 5.4 - corresponding to initial masses ~25 Msun, and final masses
as low as ~10-15 Msun. We present a census of S Doradus variability, and
discuss basic LBV properties, their mass-loss behaviour, and whether at maximum
light they form pseudo-photospheres. We argue that those objects that exhibit
giant Eta Car-type eruptions are most likely related to the more common type of
S Doradus variability. Alternative atmospheric models as well as
sub-photospheric models for the instability are presented, but the true nature
of the LBV phenomenon remains as yet elusive. We end with a discussion on the
evolutionary status of LBVs - highlighting recent indications that some LBVs
may be in a direct pre-supernova state, in contradiction to the standard
paradigm for massive star evolution.Comment: 27 pages, 6 figures, Review Chapter in "Eta Carinae and the supernova
imposters" (eds R. Humphreys and K. Davidson) new version submitted to
Springe
Weierstrass meets Enriques
We study in detail the degeneration of K3 to T^4/Z_2. We obtain an explicit
embedding of the lattice of collapsed cycles of T^4/Z_2 into the lattice of
integral cycles of K3 in two different ways. Our first method exploits the
duality to the heterotic string on T^3. This allows us to describe the
degeneration in terms of Wilson lines. Our second method is based on the
blow-up of T^4/Z_2. From this blow-up, we directly construct the full lattice
of integral cycles of K3. Finally, we use our results to describe the action of
the Enriques involution on elliptic K3 surfaces, finding that a Weierstrass
model description is consistent with the Enriques involution only in the
F-theory limit.Comment: 35 pages, 9 figure
Role of defects and disorder in the half-metallic full-Heusler compounds
Half-metallic ferromagnets and especially the full-Heusler alloys containing
Co are at the center of scientific research due to their potential applications
in spintronics. For realistic devices it is important to control accurately the
creation of defects in these alloys. We review some of our late results on the
role of defects and impurities in these compounds. More precisely we present
results for the following cases (i) doping and disorder in CoCr(Mn)Al(Si)
alloys, (ii) half-metallic ferrimagnetism appeared due to the creation of
Cr(Mn) antisites in these alloys, (iii) Co-doping in MnVAl(Si) alloys
leading to half-metallic antiferromagnetism, and finally (iv) the occurrence of
vacancies in the full-Heusler alloys containing Co and Mn. These results are
susceptible of encouraging further theoretical and experimental research in the
properties of these compounds.Comment: Chapter intended for a book with contributions of the invited
speakers of the International Conference on Nanoscale Magnetism 2007. Revised
version contains new figure
Indomethacin induces apoptosis via a MRP1-dependent mechanism in doxorubicin-resistant small-cell lung cancer cells overexpressing MRP1
Small-cell lung cancers (SCLCs) initially respond to chemotherapy, but are often resistant at recurrence. The non-steroidal anti-inflammatory drug indomethacin is an inhibitor of multidrug resistance protein 1 (MRP1) function. The doxorubicin-resistant MRP1-overexpressing human SCLC cell line GLC4-Adr was highly sensitive for indomethacin compared with the parental doxorubicin-sensitive line GLC4. The purpose of this study was to analyse the relationship between hypersensitivity to indomethacin and MRP1 overexpression. The experimental design involved analysis of the effect of MRP1 downregulation on indomethacin-induced cell survival and apoptosis in GLC4-Adr and GLC4, using siRNA. In addition the effect of indomethacin on glutathione levels and mitochondrial membrane potential was investigated. Small interfering RNAs directed against MRP1 reduced MRP1 mRNA levels twofold and reduced efflux pump function of MRP1, which was reflected by a 1.8-fold higher accumulation of MRP1 substrate carboxyfluorescein, in si-MRP1 versus si-Luciferase-transfected GLC4-Adr cells. Multidrug resistance protein 1 downregulation decreased initial high apoptosis levels 2-fold in GLC4-Adr after indomethacin treatment for 24 h, and increased cell survival (IC50) from 22.8±2.6 to 30.4±5.1 μM following continuous indomethacin exposure. Multidrug resistance protein 1 downregulation had no effect on apoptosis in GLC4 or on glutathione levels in both lines. Although indomethacin (20 μM) for 2 h decreased glutathione levels by 31.5% in GLC4-Adr, complete depletion of cellular glutathione by L-buthionine (S,R)-sulphoximine only resulted in a small increase in indomethacin-induced apoptosis in GLC4-Adr, demonstrating that a reduced cellular glutathione level is not the primary cause of indomethacin-induced apoptosis. Indomethacin exposure decreased mitochondrial membrane potential in GLC4-Adr cells, suggesting activation of the mitochondrial apoptosis pathway. Indomethacin induces apoptosis in a doxorubicin-resistant SCLC cell line through an MRP1-dependent mechanism. This may have implications for the treatment of patients with MRP1-overexpressing tumours
Beyond humanization and de-immunization: tolerization as a method for reducing the immunogenicity of biologics
Immune responses to some monoclonal antibodies (mAbs) and biologic proteins interfere with their efficacy due to the development of anti-drug antibodies (ADA). In the case of mAbs, most ADA target ‘foreign’ sequences present in the complementarity determining regions (CDRs). Humanization of the mAb sequence is one approach that has been used to render biologics less foreign to the human immune system. However, fully human mAbs can also drive immunogenicity. De-immunization (removing epitopes) has been used to reduce biologic protein immunogenicity. Here, we discuss a third approach to reducing the immunogenicity of biologics: introduction of Treg epitopes that stimulate Treg function and induce tolerance to the biologic protein. Supplementing humanization (replacing xenosequences with human) and de-immunization (reducing T effector epitopes) with tolerization (introducing Treg epitopes) where feasible, as a means of improving biologics ‘quality by design’, may lead to the development of ever more clinically effective, but less immunogenic, biologics
- …