ALICE – ITS3 — A bent, wafer-scale CMOS detector Kluge, A.
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
10/2022, Letnik:
1041
Journal Article
Recenzirano
ALICE is developing the ITS3 (inner tracker system) as upgrade of the inner layers of the presently installed ITS with the aim to improve the pointing resolution by factor of two and to lower the ...material budget to an unprecedented value of 0.05% X0 per layer.
Its three layers are based on Monolithic Active Pixel Sensors (MAPS) thinned down to 20-40 μm. The configuration employs half-cylinders, which are bent around the beam pipe with bending radii of 18, 24 and 30 mm, respectively. The sensors are produced using stitching techniques allowing to reach a length of 28 cm. As consequence, the detector consists of six MAPS sensors only. The material budget is kept to a minimum using carbon foam elements to hold the stitched sensors in place, as well as by employing airflow cooling.
This contribution summarises the achieved R&D results on bending and thinning, the mechanical prototype, beam tests and the 65 nm prototype ASIC test, as well as the path towards the last remaining milestone, the implementation of a wafer-scale, stitched sensor design.
Mitochondria and endothelial function Kluge, Matthew A; Fetterman, Jessica L; Vita, Joseph A
Circulation research,
2013-Apr-12, Letnik:
112, Številka:
8
Journal Article
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Odprti dostop
In contrast to their role in cell types with higher energy demands, mitochondria in endothelial cells primarily function in signaling cellular responses to environmental cues. This article provides ...an overview of key aspects of mitochondrial biology in endothelial cells, including subcellular location, biogenesis, dynamics, autophagy, reactive oxygen species production and signaling, calcium homeostasis, regulated cell death, and heme biosynthesis. In each section, we introduce key concepts and then review studies showing the importance of that mechanism to endothelial control of vasomotor tone, angiogenesis, and/or inflammatory activation. We particularly highlight the small number of clinical and translational studies that have investigated each mechanism in human subjects. Finally, we review interventions that target different aspects of mitochondrial function and their effects on endothelial function. The ultimate goal of such research is the identification of new approaches for therapy. The reviewed studies make it clear that mitochondria are important in endothelial physiology and pathophysiology. A great deal of work will be needed, however, before mitochondria-directed therapies are available for the prevention and treatment of cardiovascular disease.
There is a large unmet need for off-the-shelf biomaterial options to supplant venous autografts in bypass and reconstructive surgical procedures. Existing graft alternatives formed from ...non-degradable synthetic polymers are not capable of maintaining long-term patency and are thus not indicated for <6 mm inner diameter bypass procedures. To fill this void, degradable silk-based biomaterials have been proposed that can maintain their mechanical properties (i.e. compliance) while facilitating slow but progressive biomaterial remodeling and host integration mediated by cellular colonization. The goal of the present study was to enhance the porosity of gel-spun silk tubes, to facilitate faster degradation rates and improve cellularity, and thus improve host integration over time in vivo, while maintaining requisite mechanical functions. Silk solutions with a range of molecular weight distributions and, in turn, viscosities were used to generate tubes of varying porosities. A decrease in solution concentration correlated with an increase in mean pore size and overall porosity through a density-dependent mechanism. Tubes were mechanically analyzed, and these properties were the basis of an analytical model used to correlate tube formulations to structural compliance, which were shown to be similar to the saphenous vein. Tubes were also tested for suture retention to ensure surgical utility despite increased porosity. Tubes were implanted in the abdominal aorta of Sprague-Dawley rats via an end-to-end anastomosis model. Tubes with higher porosities showed early improvements in cell colonization that progressively increased over time; conversely, the dense architecture of less porous grafts (20MB) inhibited cell ingrowth and resulted in minimal biomaterial degradation at the 6-month time point. None of the highly porous tubes (5 MB and 10MB) remained patent at 6 months, likely due remodeling inducing bulk mechanical failure or a compromised blood-material interface.
Abstract Purified native silk fibroin forms β -sheet-rich, physically cross-linked, hydrogels from aqueous solution, in a process influenced by environmental parameters. Previously we reported ...gelation times of days to weeks for aqueous native silk protein solutions, with high ionic strength and temperature and low pH responsible for increasing gelation kinetics. Here we report a novel method to accelerate the process and control silk fibroin gelation through ultrasonication. Depending on the sonication parameters, including power output and time, along with silk fibroin concentration, gelation could be controlled from minutes to hours, allowing the post-sonication addition of cells prior to final gel setting. Mechanistically, ultrasonication initiated the formation of β -sheets by alteration in hydrophobic hydration, thus accelerating the formation of physical cross-links responsible for gel stabilization. K+ at physiological concentrations and low pH promoted gelation, which was not observed in the presence of Ca2+ . The hydrogels were assessed for mechanical properties and proteolytic degradation; reported values matched or exceeded other cell-encapsulating gel material systems. Human bone marrow derived mesenchymal stem cells (hMSCs) were successfully incorporated into these silk fibroin hydrogels after sonication, followed by rapid gelation and sustained cell function. Sonicated silk fibroin solutions at 4%, 8%, and 12% (w/v), followed by mixing in hMSCs, gelled within 0.5–2 h. The cells grew and proliferated in the 4% gels over 21 days, while survival was lower in the gels with higher protein content. Thus, sonication provides a useful new tool with which to initiate rapid sol–gel transitions, such as for cell encapsulation.
Silk-based blood stabilization for diagnostics Kluge, Jonathan A.; Li, Adrian B.; Kahn, Brooke T. ...
Proceedings of the National Academy of Sciences,
05/2016, Letnik:
113, Številka:
21
Journal Article
Recenzirano
Odprti dostop
Advanced personalized medical diagnostics depend on the availability of high-quality biological samples. These are typically biofluids, such as blood, saliva, or urine; and their collection and ...storage is critical to obtain reliable results. Without proper temperature regulation, protein biomarkers in particular can degrade rapidly in blood samples, an effect that ultimately compromises the quality and reliability of laboratory tests. Here, we present the use of silk fibroin as a solid matrix to encapsulate blood analytes, protecting them from thermally induced damage that could be encountered during nonrefrigerated transportation or freeze–thaw cycles. Blood samples are recovered by simple dissolution of the silk matrix in water. This process is demonstrated to be compatible with a number of immunoassays and provides enhanced sample preservation in comparison with traditional air-drying paper approaches. Additional processing can remediate interactions with conformational structures of the silk protein to further enhance blood stabilization and recovery. This approach can provide expanded utility for remote collection of blood and other biospecimens empowering new modalities of temperature- independent remote diagnostics.
Endothelial dysfunction contributes to the development of atherosclerosis in patients with diabetes mellitus, but the mechanisms of endothelial dysfunction in this setting are incompletely ...understood. Recent studies have shown altered mitochondrial dynamics in diabetes mellitus with increased mitochondrial fission and production of reactive oxygen species. We investigated the contribution of altered dynamics to endothelial dysfunction in diabetes mellitus.
We observed mitochondrial fragmentation (P=0.002) and increased expression of fission-1 protein (Fis1; P<0.0001) in venous endothelial cells freshly isolated from patients with diabetes mellitus (n=10) compared with healthy control subjects (n=9). In cultured human aortic endothelial cells exposed to 30 mmol/L glucose, we observed a similar loss of mitochondrial networks and increased expression of Fis1 and dynamin-related protein-1 (Drp1), proteins required for mitochondrial fission. Altered mitochondrial dynamics was associated with increased mitochondrial reactive oxygen species production and a marked impairment of agonist-stimulated activation of endothelial nitric oxide synthase and cGMP production. Silencing Fis1 or Drp1 expression with siRNA blunted high glucose-induced alterations in mitochondrial networks, reactive oxygen species production, endothelial nitric oxide synthase activation, and cGMP production. An intracellular reactive oxygen species scavenger provided no additional benefit, suggesting that increased mitochondrial fission may impair endothelial function via increased reactive oxygen species.
These findings implicate increased mitochondrial fission as a contributing mechanism for endothelial dysfunction in diabetic states.
Spider silks and their applications Kluge, Jonathan A; Rabotyagova, Olena; Leisk, Gary G ...
Trends in biotechnology (Regular ed.),
05/2008, Letnik:
26, Številka:
5
Journal Article
Recenzirano
Spider silks are characterized by remarkable diversity in their chemistry, structure and functions, ranging from orb web construction to adhesives and cocoons. These unique materials have prompted ...efforts to explore potential applications of spider silk equivalent to those of silkworm silks, which have undergone 5000 years of domestication and have a variety of uses, from textiles to biomedical materials. Recent progress in genetic engineering of spider silks and the development of new chimeric spider silks with enhanced functions and specific characteristics have advanced spider silk technologies. Further progress in yields of expressed spider-silk proteins, in the control of self-assembly processes and in the selective exploration of material applications is anticipated in the future. The unique features of spider silks, the progress and challenges in the cloning and expression of these silks, environmentally triggered silk assembly and disassembly and the formation of fibers, films and novel chimeric composite materials from genetically engineered spider silks will be reviewed.
Patients with oligometastatic disease can potentially be cured by using an ablative therapy for all active lesions. Stereotactic body radiotherapy (SBRT) is a non-invasive treatment option that ...lately proved to be as effective and safe as surgery in treating lung metastases (LM). However, it is not clear which patients benefit most and what are the most suitable fractionation regimens. The aim of this study was to analyze treatment outcomes after single fraction radiosurgery (SFRS) and fractionated SBRT (fSBRT) in patients with lung oligometastases and identify prognostic clinical features for better survival outcomes.
Fifty-two patients with 94 LM treated with SFRS or fSBRT between 2010 and 2016 were analyzed. The characteristics of primary tumor, LM, treatment, toxicity profiles and outcomes were assessed. Kaplan-Meier and Cox regression analyses were used for estimation of local control (LC), overall survival (OS) and progression-free survival.
Ninety-four LM in 52 patients were treated using SFRS/fSBRT with a median of 2 lesions per patient (range: 1-5). The median planning target volume (PTV)-encompassing dose for SFRS was 24 Gy (range: 17-26) compared to 45 Gy (range: 20-60) in 2-12 fractions with fSBRT. The median follow-up time was 21 months (range: 3-68). LC rates at 1 and 2 years for SFSR vs. fSBRT were 89 and 83% vs. 75 and 59%, respectively (p = 0.026). LM treated with SFSR were significantly smaller (p = 0.001). The 1 and 2-year OS rates for all patients were 84 and 71%, respectively. In univariate analysis treatment with SFRS, an interval of ≥12 months between diagnosis of LM and treatment, non-colorectal cancer histology and BED < 100 Gy were significantly associated with better LC. However, none of these parameters remained significant in the multivariate Cox regression model. OS was significantly better in patients with negative lymph nodes (N0), Karnofsky performance status (KPS) > 70% and time to first metastasis ≥12 months. There was no grade 3 acute or late toxicity.
Longer time to first metastasis, good KPS and N0 predicted better OS. Good LC and low toxicity rates were achieved after short SBRT schedules.
Aorto-atrial fistula is a rare and life-threatening complication of infective endocarditis, classically diagnosed by visualizing a connection between the aorta and atrium with associated continuous ...flow. A patient presented with bioprosthetic and native valve enterococcal endocarditis with multiple complications, including an aorto-atrial fistula that was diagnosed by color M-mode on transesophageal echocardiography. We review the features of aorto-atrial fistula and utilize this case to demonstrate how M-mode can be leveraged to provide improved temporal resolution in the setting of diagnostic uncertainty.
TDCpix pixel detector ASIC with 100 ps time stamping Rinella, G. Aglieri; Bonacini, S.; Jarron, P. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
08/2023, Letnik:
1053
Journal Article
Recenzirano
Odprti dostop
The TDCpix pixel read-out ASIC contains 1800 pixels arranged in 40 columns and 45 rows with the dimension of 300μm x 300μm. Each pixel contains a preamplifier and shaper circuit with a dynamic range ...of 0.8 to 10 fC and a rise time of 5 ns, followed by a Leading-Edge discriminator with Time-over-Threshold correction. The discriminator outputs of each pixel are connected to time-to-digital converters (TDC) measuring the time when the input signal has exceeded the threshold and the pulse width with a binning of 97 ps. The electronics noise of pre-amplifier/shaper is 170 e− or 2.7 mV rms with a gain of 65 mV/fC. The jitter of the entire processing chain for an electrical input signal of 2.4 fC is lower than 60 ps rms. The ASIC has been designed to work in radiated environments of 6 * 104 Gray per year and 2 x 1014 1 MeV neutron equivalent cm−2.
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