There is growing evidence supporting the role of inflammation in early brain injury and cerebral vasospasm following subarachnoid hemorrhage (SAH). Matrix metalloproteinases (MMPs) are released by ...inflammatory cells and can mediate early brain injury via disruption of the extracellular matrix and mediate vasospasm by cleaving endothelin-1 into vasoactive fragments. We hypothesize that inflammation marked by neutrophil elevation and MMP-9 release in human SAH is associated with vasospasm and with poor clinical outcome. We enrolled consecutive SAH subjects (
N
= 55), banked serial blood and cerebrospinal fluid (CSF) samples, and evaluated their 3-month modified Rankin scores (mRS). Vasospasm was defined as >50% vessel caliber reduction on angiography 6–8 days post-SAH. A poor outcome was defined as mRS > 2. We compared blood leukocyte and neutrophil counts during post-SAH days 0–14 with respect to vasospasm and 3-month outcome. In a subset of SAH subjects (
N
= 35), we compared blood and CSF MMP-9 by enzyme-linked immunosorbent assay (ELISA) on post-SAH days 0–1, 2–3, 4–5, 6–8, and 10–14 with respect to vasospasm and to 3-month outcome. Persistent elevation of blood leukocyte (
p
= 0.0003) and neutrophil (
p
= 0.0002) counts during post-SAH days 0–14 are independently associated with vasospasm after adjustment for major confounders. In the same time period, blood neutrophil count (post-SAH days 2–3,
p
= 0.018), blood MMP-9 (post-SAH days 4–5,
p
= 0.045), and CSF MMP-9 (post-SAH days 2–3,
p
= 0.05) are associated with poor 3-month SAH clinical outcome. Neutrophil count correlates with blood MMP-9 (post-SAH days 6–8,
R
= 0.39;
p
= 0.055; post-SAH days 10–14,
R
= 0.79;
p
< 0.0001), and blood MMP-9 correlates with CSF MMP-9 (post-SAH days 4–5,
R
= 0.72;
p
= 0.0002). Elevation of CSF MMP-9 during post-SAH days 0–14 is associated with poor 3-month outcome (
p
= 0.0078). Neither CSF nor blood MMP-9 correlates with vasospasm. Early rise in blood neutrophil count and blood and CSF MMP-9 are associated with poor 3-month SAH clinical outcome. In blood, neutrophil count correlates with MMP-9 levels, suggesting that neutrophils may be an important source of blood MMP-9 early in SAH. Similarly, CSF and blood MMP-9 correlate positively early in the course of SAH, suggesting that blood may be an important source of CSF MMP-9. Blood and CSF MMP-9 are associated with clinical outcome but not with vasospasm, suggesting that MMP-9 may mediate brain injury independent of vasospasm in SAH. Future in vitro studies are needed to investigate the role of MMP-9 in SAH-related brain injury. Larger clinical studies are needed to validate blood and CSF MMP-9 as potential biomarkers for SAH outcome.
The performance of the CDF luminosity monitor Acosta, D; Klimenko, S; Konigsberg, J ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
11/2002, Letnik:
494, Številka:
1
Journal Article
Recenzirano
We describe the initial performance of the detector used for the luminosity measurement in the CDF experiment in Run II at the Tevatron. The detector consists of low-mass gaseous Cherenkov counters ...with high light yield (∼100 photoelectrons) and monitors the process of inelastic
p
p
̄
scattering. It allows for several methods of precise luminosity measurements at peak instantaneous luminosities of
2×10
32
cm
−2
s
−1
, corresponding to an average of six
p
p
̄
interactions per bunch crossing.
A Time-of-Flight detector in CDF-II Acosta, D.; Ahn, M.; Anikeev, K. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
02/2004, Letnik:
518, Številka:
1
Journal Article
Recenzirano
A Time-of-Flight (TOF) detector, based on plastic scintillators and fine-mesh photomultipliers, has been added to the Collider Detector at Fermilab (CDF)-II experiment at the Tevatron
p
p
̄
collider. ...The primary physics motivation is to provide charged kaon identification to improve neutral B meson flavor determination. Besides that, the TOF detector found application in the CDF trigger system in implementation of highly ionizing particle, high multiplicity and cosmic rays triggers.
A high-performance track fitter for use in ultra-fast electronics Clement, E.; De Mattia, M.; Dutta, S. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
08/2019, Letnik:
935
Journal Article
Recenzirano
Odprti dostop
This article describes a new charged-particle track fitting algorithm designed for use in high-speed electronics applications such as hardware-based triggers in high-energy physics experiments. ...Following a novel technique designed for fast electronics, the positions of the hits on the detector are transformed before being passed to a linearized track parameter fit. This transformation results in fitted track parameters with a very linear dependence on the hit positions. The approach is demonstrated in a representative detector geometry based on the CMS detector at the Large Hadron Collider. The fit is implemented in FPGA chips and optimized for track fitting throughput and obtains excellent track parameter performance. Such an algorithm is potentially useful in any high-speed track-fitting application.
The CDF Cherenkov luminosity monitor Acosta, D.; Klimenko, S.; Konigsberg, J. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
04/2001, Letnik:
461, Številka:
1
Journal Article
Recenzirano
We have built a novel device for precision measurements of luminosity in the CDF experiment at the high
p
p
̄
collision rates expected during Run II. The detector consists of long, conical, gaseous ...Cherenkov counters that point to the collision region and monitor the average number of inelastic
p
p
̄
interactions by measuring the number of particles, and their arrival time, in each bunch crossing. For these primary particles, using isobutane at atmospheric pressure as a radiator, a large amount of Cherenkov light (∼100 photoelectrons) will be collected, with good amplitude and time resolutions, onto small and efficient PMTs. Suitable amplitude thresholds will be applied to discriminate from non-primary particles and other backgrounds which yield little light in the counters. This detector is expected to reliably perform bunch-by-bunch luminosity measurements at peak instantaneous luminosities of 2×10
32
cm
−2
s
−1 with six interactions per bunch crossing, on average, and respond to a 132
ns bunch spacing.
The cytoplasmic, dense granules of cloned T cell lines were isolated and analyzed for their functional and biochemical properties. Isolated granules of approximately 90% homogeneity, in the presence ...of Ca, effect strong tumoricidal and hemolytic activity. Tumor cell lysis is complete in less than 30 min, with less than 2 micrograms granule protein corresponding to a killer/target ratio of 3-6:1 by assuming 50% yield for granule isolation. The granules contain a set of unique proteins, responsible for cytolytic activity and designated K1 to K6, in the molecular weight range of 14,000 to 75,000, as defined by sodium dodecyl sulfate (SDS) polyacrylamide slab gel analysis under reducing and nonreducing conditions. Cytolysis mediated by isolated granules is accompanied by the assembly of tubular complexes of 160 A (poly P1) and of approximately 70 A width (poly P2) that are inserted into membranes and form ultrastructural membrane lesions. As shown by immunofluorescence and by Percoll gradient fractionation, cytolytic granules are detected in cells of cytolytic T cell lineage and not in the T cell lymphomas E14 and S194. Poly perforin 1 assembled by CTLL-2 upon stimulation with concanavalin A (Con A) and phorbol myristate acetate (PMA) was isolated by detergent extraction and gel filtration. Poly P1 is composed of disulfide-linked subunits that, after reduction, co-migrate with certain granule proteins. The results are compatible with the hypothesis that the dense granules of cytolytic T cells contain cytolytic proteins that polymerize to disulfide-linked tubular poly perforins in a Ca-dependent reaction and may cause cytolysis by membrane insertion and transmembrane channel formation.
A unique immunoliposome has been developed as a drug delivery vehicle for immunotherapy. Human recombinant interleukin-2 (IL-2) has been chemically coupled to the external surface of small ...unilamellar vesicles (SUVs) containing methotrexate as a candidate immunosuppresive agent in order to specifically direct the drug-bearing liposome to activated T-cells expressing the high affinity IL-2 receptor. This drug delivery system is designed to deliver an immunosuppressive agent to those cells that actively participate in disorders such as graft rejection without delivering an effective but potentially toxic drug to all cells of the immune system as well as other healthy tissues. IL-2 was chemically modified with succinimidyl 4-
p-maleidophenyl butyrate(SMPB) while the receptor binding domain on IL-2 was protected by monoclonal anti-IL-2 bound to Protein A-Silica Gel. The antibody recognizes the
receptor binding domain
of the IL-2 molecule. The IL-2 was derivatized with S-succinimidyl-S-thioacetate (SATA) in order to add an acetyl thioester group to the lipid and create the complex. The derivatized lipid (SATA-PE) was then part of the liposome formulation containing DSPC:cholesterol: SATA-PE at a mole ratio of 1.5:1.0:0.26. SMPB-IL-2 was covalently coupled to the external surface of the SUV after deacetylation of the thioester moiety at pH 7.4 in PBS. Liposomes prepared by sonication or extrusion had an average diameter of 46–50 nm. SUV-IL-2 bound to the high affinity IL-2 receptor as measured by competitive binding assays and Scatchard analysis using
111InCl
2-loaded liposomes The preparation exhibited a binding constant of 30 pM, consistent with values for free IL-2 cited in the literature. SUV IL-2 could be used as the sole source of IL-2 for the murine CTLL-2 T-cell line or for human mitogen-activated PBLs. The presence of IL-2 coupled to the surface was absolutely required for delivery of the drug to the cell. When methotrexate was encapsulated within the internal aqueous space, receptor-mediated endocytosis led to the inhibition of proliferation due to delivery of MTX to the cytoplasm of the cell. More than 90% of the methotrexate was retained within the liposome during storage over a 24-h period at 4°C. This immunoliposome represents a new class of cell specific immunoliposomes whose entry into the cell is controlled by a cell surface receptor.
Luminosity monitor based on Cherenkov counters for pp̄ colliders Elias, J; Klimenko, S; Konigsberg, J ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
03/2000, Letnik:
441, Številka:
3
Journal Article
Recenzirano
We describe here a novel approach to luminosity measurements for
p
p
̄
collider experiments. We propose to use low-pressure gaseous Cherenkov counters at small angles relative to the beam direction ...to determine the rate of inelastic
p
p
̄
interactions. With a propotype counter, we measured at a beam test a light yield of over 100 photoelectrons and a timing resolution of better than 50 ps. The CDF collaboration will use a detector based on this technique for luminosity measurements at the upgraded Tevatron collider.
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