180 research outputs found
High Spatial Resolution Fast-Neutron Imaging Detectors for Pulsed Fast-Neutron Transmission Spectroscopy
Two generations of a novel detector for high-resolution transmission imaging
and spectrometry of fast-neutrons are presented. These devices are based on a
hydrogenous fiber scintillator screen and single- or multiple-gated intensified
camera systems (ICCD). This detector is designed for energy-selective neutron
radiography with nanosecond-pulsed broad-energy (1 - 10 MeV) neutron beams.
Utilizing the Time-of-Flight (TOF) method, such a detector is capable of
simultaneously capturing several images, each at a different neutron energy
(TOF). In addition, a gamma-ray image can also be simultaneously registered,
allowing combined neutron/gamma inspection of objects. This permits combining
the sensitivity of the fast-neutron resonance method to low-Z elements with
that of gamma radiography to high-Z materials.Comment: Also published in JINST:
http://www.iop.org/EJ/abstract/1748-0221/4/05/P0501
Mitochondrial damage-associated molecular patterns (DAMPs) in inflammatory bowel disease
Background
The inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohn’s
disease (CD) are chronic relapsing inflammatory disorders which have a rising
incidence and cause significant morbidity. There are currently several
treatment options with many more in the drug pipeline, but there are a lack of
accurate biomarkers for decisions on treatment choice, assessment of disease
activity and prognostication. There is a growing interest and desire for
personalised or ‘precision’ medicine in IBD where novel biomarkers may help
individualise IBD care in terms of diagnosis, choice of therapy, monitoring of
response and detection of relapse. One class of functionally active biomarkers
which have yet to be thoroughly investigated in IBD is damage-associated
molecular patterns (DAMPs) including mitochondrial DNA (mtDNA). It has
been recently shown that gut mitochondrial dysfunction can result in loss of
epithelial barrier function and the development of colitis. Mitochondrial DAMPs
have recently been described as elevated in several inflammatory diseases.
Hypothesis
The primary hypothesis of this thesis is that circulating levels of mtDNA is
elevated in IBD. Secondary hypotheses are: (a) levels of other mitochondrial
DAMPs are elevated in IBD, (b) circulating mtDNA can be used as a novel
biomarker in IBD and (c) mtDNA is released locally at sites of inflammation in
IBD.
Methods
Plasma and serum were collected prospectively from recruited IBD patients
and non-IBD controls. Faeces and colonic tissue were collected from a subset
of these patients. mtDNA in serum, plasma and faeces was measured using
qPCR (amplifying COXIII/ND2 genes). Mass spectrometry was used to detect
mitochondrial formylated peptides in the plasma of a subset of patients. IBD
tissue was assessed for (a) mitochondrial damage using transmission electron
microscopy (TEM) and (b) TLR9 expression, the target for mtDNA.
Results
97 patients with IBD (67 UC and 30 CD), and 40 non-IBD controls were
recruited. Plasma mtDNA levels were increased in UC and CD (both p<0.0001)
compared to non-IBD controls; with significant correlations with blood (CRP,
albumin, white cell count), clinical and endoscopic markers of severity; and
disease activity. In active UC, we detected significantly higher circulating
mitochondrial formylated peptides and faecal mtDNA levels (vs. non-IBD
controls [p<0.01 and <0.0001 respectively]) with demonstrable TEM evidence
of intestinal mucosal mitochondrial damage. In active IBD, TLR9+ lamina
propria inflammatory cells were significantly higher in UC/CD compared to
controls (both p<0.05).
Conclusions
Taken together, the findings suggest mtDNA is released during active
inflammation in inflammatory bowel disease and is a potential novel
mechanistic biomarker
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