Here we report the results of the first ever contemporaneous multi-wavelength observation campaign on the BL Lac object PKS 2155−304 involving Swift, NuSTAR, Fermi-LAT, and H.E.S.S. The use of these ...instruments allows us to cover a broad energy range, which is important for disentangling the different radiative mechanisms. The source, observed from June 2013 to October 2013, was found in a low flux state with respect to previous observations but exhibited highly significant flux variability in the X-rays. The high-energy end of the synchrotron spectrum can be traced up to 40 keV without significant contamination by high-energy emission. A one-zone synchrotron self-Compton model was used to reproduce the broadband flux of the source for all the observations presented here but failed for previous observations made in April 2013. A lepto-hadronic solution was then explored to explain these earlier observational results.
Objective. Accumulating evidence suggests that B-cell depletion therapy by rituximab may be effective for autoimmune disorders. However, an optimal dose of rituximab and a mechanism of its action ...remain to be established. We performed a dose-escalation study for treatment of Japanese patients with autoimmune diseases including eight with SLE and one with Evans’ syndrome. Methods. Rituximab was infused intravenously, weekly 4 times in a dose-escalating fashion at three different doses of 100, 250 or 375 mg/m2 to three patients each. Immunological parameters were monitored at certain points until 12 months after the treatment. Results. Rituximab was well tolerated and safe in these patients. Seven out of eight SLE patients and one with Evans’ syndrome clinically responded completely or partially to the treatment. Four patients achieved long-term remission (18–30 months) without any additional treatment. In these patients, a significant decrease in circulating B cells continued for 6 months after the treatment. The mean fluorescence intensities of CD19, CD21, CD40 and BR3 on the residual B cells as well as the percentage of CD69+ CD4+ T cells decreased significantly. Serum TNF-α levels decreased significantly on day 2. The Th1/Th2 balance of CD4+ T cells gradually shifted towards a Th1 type by 6 months. Conclusion. In addition to B-cell depletion, modification of B-cell and T-cell phenotypes as well as cytokine profiles may be involved in the action of rituximab.
Despite being heavily exploited, pangolins (Pholidota: Manidae) have been subject to
limited research, resulting in a lack of reliable population estimates and standardised
survey methods for the ...eight extant species. Camera trapping represents a unique opportunity
for broad-scale collaborative species monitoring due to its largely nondiscriminatory
nature, which creates considerable volumes of data on a relatively wide
range of species. This has the potential to shed light on the ecology of rare, cryptic and
understudied taxa, with implications for conservation decision-making. We undertook a
global analysis of available pangolin data from camera trapping studies across their range
in Africa and Asia. Our aims were (1) to assess the utility of existing camera trapping efforts
as a method for monitoring pangolin populations, and (2) to gain insights into the distribution
and ecology of pangolins. We analysed data collated from 103 camera trap surveys
undertaken across 22 countries that fell within the range of seven of the eight
pangolin species, which yielded more than half a million trap nights and 888 pangolin
encounters. We ran occupancy analyses on three species (Sunda pangolin Manis javanica,
white-bellied pangolin Phataginus tricuspis and giant pangolin Smutsia gigantea). Detection
probabilities varied with forest cover and levels of human influence for P. tricuspis, but were low (<0.05) for all species. Occupancy was associated with distance from rivers for M.
javanica and S. gigantea, elevation for P. tricuspis and S. gigantea, forest cover for P. tricuspis
and protected area status for M. javanica and P. tricuspis.We conclude that camera traps are
suitable for the detection of pangolins and large-scale assessment of their distributions.
However, the trapping effort required to monitor populations at any given study site using
existing methods appears prohibitively high. This may change in the future should
anticipated technological and methodological advances in camera trapping facilitate
greater sampling efforts and/or higher probabilities of detection. In particular, targeted
camera placement for pangolins is likely to make pangolin monitoring more feasible with
moderate sampling efforts.
Background: Regenerating gene type IV (RegIV) is a candidate marker for cancer and inflammatory bowel disease. In this study,
its potential as a novel marker for the detection of gastric cancer ...peritoneal micrometastases was examined. Patients and
Methods: RegIV mRNA levels in the peritoneal washes of 95 gastric cancer patients and 22 with benign disease were quantified
by real-time RT-PCR. To examine whether expression of RegIV enhance tumorigenicity or not, thirty two mice were injected intraperitoneally
or subcutaneously with RegIV transfectants of TMK-1 cells, parental TMK-1 cells, or neomycin control transfectants. Results:
RegIV expression was markedly higher in patients with peritoneal metastases compared to those without. The level of RegIV
mRNA in gastric cancer patients was related to the extent of wall penetration. A cut-off value for RegIV-positive expression
was based on an analysis of negative control patients with benign disease, and gastric cancer patients above the cut-off value
constituted the micrometastasis (MM+) group. Based on this criteria, 3 out of 43 T1 or T2 cases were MM+ (93% specificity).
Among 15 patients with peritoneal dissemination (7 out of 15 cases were positive by cytology), 14 cases were positive for
RegIV expression (93% sensitivity), while analysis of carcinoembryonic antigen (CEA) mRNA failed to detect micrometastases
in 4 cases (73% sensitivity). Combined analysis of CEA and RegIV improved the accuracy of diagnosis to 100%. The prognosis
of RegIV-positive cases was significantly worse than that of RegIV-negative cases. Multivariate analysis using the Cox proportional
hazards model suggested that RegIV may be an independent prognostic factor. Stable expression of RegIV significantly enhanced
peritoneal metastasis in an animal model of gastric cancer. Conclusion: These findings suggest that RegIV mRNA expression
has the potential to serve as a novel marker for detecting peritoneal dissemination in gastric cancer.
The H.E.S.S. Collaboration has discovered a new very high energy (VHE, E > 0.1 TeV) γ-ray source, HESS J1741−302, located in the Galactic plane. Despite several attempts to constrain its nature, no ...plausible counterpart has been found so far at X-ray and MeV/GeV γ-ray energies, and the source remains unidentified. An analysis of 145-h of observations of HESS J1741−302 at VHEs has revealed a steady and relatively weak TeV source (~1% of the Crab Nebula flux), with a spectral index of Γ = 2.3 ± 0.2stat ± 0.2sys, extending to energies up to 10 TeV without any clear signature of a cut-off. In a hadronic scenario, such a spectrum implies an object with particle acceleration up to energies of several hundred TeV. Contrary to most H.E.S.S. unidentified sources, the angular size of HESS J1741−302 is compatible with the H.E.S.S. point spread function at VHEs, with an extension constrained to be below 0.068° at a 99% confidence level. The γ-ray emission detected by H.E.S.S. can be explained both within a hadronic scenario, due to collisions of protons with energies of hundreds of TeV with dense molecular clouds, and in a leptonic scenario, as a relic pulsar wind nebula, possibly powered by the middle-aged (20 kyr) pulsar PSR B1737−30. A binary scenario, related to the compact radio source 1LC 358.266+0.038 found to be spatially coincident with the best fit position of HESS J1741−302, is also envisaged.
A subset of Alzheimer disease cases is caused by autosomal dominant mutations in genes encoding the amyloid β-protein precursor or presenilins. Whereas some amyloid β-protein precursor mutations ...alter its metabolism through effects on Aβ production, the pathogenic effects of those that alter amino acid residues within the Aβ sequence are not fully understood. Here we examined the biophysical effects of two recently described intra-Aβ mutations linked to early-onset familial Alzheimer disease, the D7N Tottori-Japanese and H6R English mutations. Although these mutations do not affect Aβ production, synthetic Aβ(1-42) peptides carrying D7N or H6R substitutions show enhanced fibril formation. In vitro analysis using Aβ(1-40)-based mutant peptides reveal that D7N or H6R mutations do not accelerate the nucleation phase but selectively promote the elongation phase of amyloid fibril formation. Notably, the levels of protofibrils generated from D7N or H6R Aβ were markedly inhibited despite enhanced fibril formation. These N-terminal Aβ mutations may accelerate amyloid fibril formation by a unique mechanism causing structural changes of Aβ peptides, specifically promoting the elongation process of amyloid fibrils without increasing metastable intermediates.
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