High-Rate Data-Capture for an Airborne Lidar System

A high-rate data system was required to capture the data for an airborne lidar system. A data system was developed that achieved up to 22 million (64-bit) events per second sustained data rate (1408 million bits per second), as well as short bursts (less than 4 s) at higher rates. All hardware used for the system was off the shelf, but carefully selected to achieve these rates. The system was used to capture laser fire, single-photon detection, and GPS data for the Slope Imaging Multi-polarization Photo-counting Lidar (SIMPL). However, the system has applications for other laser altimeter systems (waveform-recording), mass spectroscopy, xray radiometry imaging, high-background- rate ranging lidar, and other similar areas where very high-speed data capture is needed. The data capture software was used for the SIMPL instrument that employs a micropulse, single-photon ranging measurement approach and has 16 data channels. The detected single photons are from two sources those reflected from the target and solar background photons. The instrument is non-gated, so background photons are acquired for a range window of 13 km and can comprise many times the number of target photons. The highest background rate occurs when the atmosphere is clear, the Sun is high, and the target is a highly reflective surface such as snow. Under these conditions, the total data rate for the 16 channels combined is expected to be approximately 22 million events per second. For each photon detection event, the data capture software reads the relative time of receipt, with respect to a one-per-second absolute time pulse from a GPS receiver, from an event timer card with 0.1-ns precision, and records that information to a RAID (Redundant Array of Independent Disks) storage device. The relative time of laser pulse firings must also be read and recorded with the same precision. Each of the four event timer cards handles the throughput from four of the channels. For each detection event, a flag is recorded that indicates the source channel. To accommodate the expected maximum count rate and also handle the other extreme of very low rates occurring during nighttime operations, the software requests a set amount of data from each of the event timer cards and buffers the data. The software notes if any of the cards did not return all the data requested and then accommodates that lower rate. The data is buffered to minimize the I/O overhead of writing the data to storage. Care was taken to optimize the reads from the cards, the speed of the I/O bus, and RAID configuration

Open repair of chronic thoracic and thoracoabdominal aortic dissection using deep hypothermia and circulatory arrest

Background Chronic dissection of the thoracic and thoracoabdominal aorta as sequela of a prior type A or B dissection is a challenging problem that requires close radiographic surveillance and prompt operative intervention in the presence of symptoms or aneurysm formation. Open repair of chronic thoracic and thoracoabdominal aortic dissection using deep hypothermia has been our preferred method to treat this complex pathology. The advantages of this technique include organ and spinal cord protection, the flexibility to extend the repair proximally into the arch, and the ability to limit ischemia to all vascular beds. Methods Open repair of arch by left thoracotomy and descending thoracic and thoracoabdominal aortic pathology using deep hypothermia was performed in 664 patients from 1995 to 2015. A subset of this cohort had chronic thoracoabdominal aortic dissection (n = 196). All nonemergency cases received coronary angiography and echocardiography preoperatively. Significant coronary artery disease or severe aortic insufficiency was addressed before repair of the chronic dissection. In recent years, lumbar drains were placed preoperatively in the most extensive repairs (extents II and III). Important intercostal arteries from T8 to L1 were revascularized with smaller-diameter looped grafts. Multibranched grafts for the visceral segment have been preferred in recent years. Results Mean age of patients was 58 ± 14 years. Men comprised 74% of the cohort. Aortopathy was confirmed in 18% of the cohort. Prior thoracic aortic repair occurred in 57% of patients, and prior abdominal aortic repair occurred in 14% of patients. Prior type A aortic dissection occurred in 44% of patients, and prior type B occurred in 56% of patients. Operative mortality was 3.6%, permanent spinal cord ischemia occurred in 2.6% of patients, permanent hemodialysis occurred in 0% of patients, and permanent stroke occurred in 1% of patients. Reexploration for bleeding was 5.1%, and respiratory failure requiring tracheostomy occurred in 2.6%. Postoperative length of stay was 11.9 ± 9.7 days. Reintervention for pseudoaneurysm or growth of a distal aneurysm was 6.9%. The 1-, 5-, and 10-year survivals were 93%, 79%, and 57%, respectively. Conclusions Open repair of chronic thoracic and thoracoabdominal aortic dissection using deep hypothermia and circulatory arrest has low morbidity and mortality. The need for reintervention is low, and long-term survival is excellent. We believe that open repair continues to be the gold standard in patients who are suitable candidates for surgery

Rapid kit-based (68)Ga-labelling and PET imaging with THP-Tyr(3)-octreotate:a preliminary comparison with DOTA-Tyr(3)-octreotate

BACKGROUND: Ge/(68)Ga generators provide an inexpensive source of a PET isotope to hospitals without cyclotron facilities. The development of new (68)Ga-based molecular imaging agents and subsequent clinical translation would be greatly facilitated by simplification of radiochemical syntheses. We report the properties of a tris(hydroxypyridinone) conjugate of the SSTR2-targeted peptide, Tyr(3)-octreotate (TATE), and compare the (68)Ga-labelling and biodistribution of [(68)Ga(THP-TATE)] with the clinical radiopharmaceutical [(68)Ga(DOTATATE)]. METHODS: A tris(hydroxypyridinone) with a pendant isothiocyanate group was conjugated to the primary amine terminus of H(2)N-PEG(2)-Lys(iv-Dde)(5)-TATE, and the resulting conjugate was deprotected to provide THP-TATE. THP-TATE was radiolabelled with (68)Ga(3+) from a (68)Ge/(68)Ga generator. In vitro uptake was assessed in SSTR2-positive 427-7 cells and SSTR2-negative 427 (parental) cells. Biodistribution of [(68)Ga(THP-TATE)] was compared with that of [(68)Ga(DOTATATE)] in Balb/c nude mice bearing SSTR2-positive AR42J tumours. PET scans were obtained 1 h post-injection, after which animals were euthanised and tissues/organs harvested and counted. RESULTS: [(68)Ga(THP-TATE)] was radiolabelled and formulated rapidly in <2 min, in ≥95 % radiochemical yield at pH 5–6.5 and specific activities of 60–80 MBq nmol(−1) at ambient temperature. [(68)Ga(THP-TATE)] was rapidly internalised into SSTR2-positive cells, but not SSTR2-negative cells, and receptor binding and internalisation were specific. Animals administered [(68)Ga(THP-TATE)] demonstrated comparable SSTR2-positive tumour activity (11.5 ± 0.6 %ID g(−1)) compared to animals administered [(68)Ga(DOTATATE)] (14.4 ± 0.8 %ID g(−1)). Co-administration of unconjugated Tyr(3)-octreotate effectively blocked tumour accumulation of [(68)Ga(THP-TATE)] (2.7 ± 0.6 %ID g(−1)). Blood clearance of [(68)Ga(THP-TATE)] was rapid and excretion was predominantly renal, although compared to [(68)Ga(DOTATATE)], [(68)Ga(THP-TATE)] exhibited comparatively longer kidney retention. CONCLUSIONS: Radiochemical synthesis of [(68)Ga(THP-TATE)] is significantly faster, proceeds under milder conditions, and requires less manipulation than that of [(68)Ga(DOTATATE)]. A (68)Ga-labelled tris(hydroxypyridinone) conjugate of Tyr(3)-octreotate demonstrates specificity and targeting affinity for SSTR2 receptors, with comparable in vivo targeting affinity to the clinical PET tracer, [(68)Ga(DOTATATE)]. Thus, peptide conjugates based on tris(hydroxypyridinones) are conducive to translation to kit-based preparation of PET tracers, enabling the expansion and adoption of (68)Ga PET in hospitals and imaging centres without the need for costly automated synthesis modules

Defective mitochondrial peroxiredoxin-3 results in sensitivity to oxidative stress in Fanconi anemia

Cells from patients with Fanconi anemia (FA), an inherited disorder that includes bone marrow failure and cancer predisposition, have increased sensitivity to oxidative stress through an unknown mechanism. We demonstrate that the FA group G (FANCG) protein is found in mitochondria. Wild-type but not G546R mutant FANCG physically interacts with the mitochondrial peroxidase peroxiredoxin-3 (PRDX3). PRDX3 is deregulated in FA cells, including cleavage by a calpainlike cysteine protease and mislocalization. FA-G cells demonstrate distorted mitochondrial structures, and mitochondrial extracts have a sevenfold decrease in thioredoxin-dependent peroxidase activity. Transient overexpression of PRDX3 suppresses the sensitivity of FA-G cells to H2O2, and decreased PRDX3 expression increases sensitivity to mitomycin C. Cells from the FA-A and -C subtypes also have PRDX3 cleavage and decreased peroxidase activity. This study demonstrates a role for the FA proteins in mitochondria witsh sensitivity to oxidative stress resulting from diminished peroxidase activity. These defects may lead to apoptosis and the accumulation of oxidative DNA damage in bone marrow precursors