Calibrating and testing tissue equivalent proportional counters with 37Ar

A method for testing and calibrating tissue equivalent proportional counters with37Ar is described.37Ar is produced by exposure of argon in its normal isotope composition to thermal neutrons. It is shown that - up to volume ratios of 0.01 of argon to the tissue equivalent gas - there is no appreciable effect of the argon admixture on the function of the proportional counter. Conventional calibration methods with characteristic x-rays or with -particles require modifications of the detectors, and they test only small sub-volumes in the counters. In contrast, argon permits calibrations and tests of the resolution that are representative for the entire counter volume and that do not require changes in detector construction. The method is equally applicable to multi-element proportional counters; it is here exemplified by its application to a long cylindrical counter of simplified design that is part of such a multi-element configuration

Radially restricted linear energy transfer for high-energy protons: A new analytical approach

Radially restricted linear energy transfer (LET) is a basic physical parameter relevant to radiation biology and radiation protection. In this report a convenient method is presented for the analytical computation of this quantity without the need for complicated simulation. The method uses the energy-re-stricted LETL, as recently redefined in a 1993 ICRU draft document and supplements it by a relatively simple term that represents the energy of fast rays lost within distancer from the track core. The method provides a better fit than other models and is valid over the entire range of radial distance from track center to the maximum radial distance traveled by the most energetic secondary electrons.L r computed by this approach differs only a few percent from the values Contribution to the international symposium on heavy ions research: space, radiation protection and therapy, 21–24 March 1994, Sophia-Antipolis, Franc

Methylglyoxal-dependent glycative stress and deregulation of SIRT1 functional network in the ovary of PCOS mice

Advanced glycation end-products (AGEs) are involved in the pathogenesis and consequences of polycystic ovary syndrome (PCOS), a complex metabolic disorder associated with female infertility. The most powerful AGE precursor is methylglyoxal (MG), a byproduct of glycolysis, that is detoxified by the glyoxalase system. By using a PCOS mouse model induced by administration of dehydroepiandrosterone (DHEA), we investigated whether MG-dependent glycative stress contributes to ovarian PCOS phenotype and explored changes in the Sirtuin 1 (SIRT1) functional network regulating mitochondrial functions and cell survival. In addition to anovulation and reduced oocyte quality, DHEA ovaries revealed altered collagen deposition, increased vascularization, lipid droplets accumulation and altered steroidogenesis. Here we observed increased intraovarian MG-AGE levels in association with enhanced expression of receptor for AGEs (RAGEs) and deregulation of the glyoxalase system, hallmarks of glycative stress. Moreover, DHEA mice exhibited enhanced ovarian expression of SIRT1 along with increased protein levels of SIRT3 and superoxide dismutase 2 (SOD2), and decreased peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC1 alpha), mitochondrial transcriptional factor A (mtTFA) and translocase of outer mitochondrial membrane 20 (TOMM20). Finally, the presence of autophagy protein markers and increased AMP-activated protein kinase (AMPK) suggested the involvement of SIRT1/AMPK axis in autophagy activation. Overall, present findings demonstrate that MG-dependent glycative stress is involved in ovarian dysfunctions associated to PCOS and support the hypothesis of a SIRT1-dependent adaptive response

Crosstalk between the ubiquitin-proteasome system and autophagy in a human cellular model of Alzheimer's disease

Alzheimer's disease is the most common progressive neurodegenerative disorder characterized by the abnormal deposition of amyloid plaques, likely as a consequence of an incorrect processing of the amyloid-β precursor protein (AβPP). Dysfunctions in both the ubiquitin-proteasome system and autophagy have also been observed. Recently, an extensive cross-talk between these two degradation pathways has emerged, but the exact implicated processes are yet to be clarified. In this work, we gained insight into such interplay by analyzing human SH-SY5Y neuroblastoma cells stably transfected either with wild-type AβPP gene or 717 valine-to-glycine AβPP-mutated gene. The over-expression of the AβPP mutant isoform correlates with an increase in oxidative stress and a remodeled pattern of protein degradation, with both marked inhibition of proteasome activities and impairment in the autophagic flux. To compensate for this altered scenario, cells try to promote the autophagy activation in a HDAC6-dependent manner. The treatment with amyloid-β(42) oligomers further compromises proteasome activity and also contributes to the inhibition of cathepsin-mediated proteolysis, finally favoring the neuronal degeneration and suggesting the existence of an Aβ(42) threshold level beyond which proteasome-dependent proteolysis becomes definitely dysfunctional

Preliminary definitions for the sonographic features of synovitis in children

Objectives Musculoskeletal ultrasonography (US) has the potential to be an important tool in the assessment of disease activity in childhood arthritides. To assess pathology, clear definitions for synovitis need to be developed first. The aim of this study was to develop and validate these definitions through an international consensus process. Methods The decision on which US techniques to use, the components to be included in the definitions as well as the final wording were developed by 31 ultrasound experts in a consensus process. A Likert scale of 1-5 with 1 indicating complete disagreement and 5 complete agreement was used. A minimum of 80% of the experts scoring 4 or 5 was required for final approval. The definitions were then validated on 120 standardized US images of the wrist, MCP and tibiotalar joints displaying various degrees of synovitis at various ages. Results B-Mode and Doppler should be used for assessing synovitis in children. A US definition of the various components (i.e. synovial hypertrophy, effusion and Doppler signal within the synovium) was developed. The definition was validated on still images with a median of 89% (range 80-100) of participants scoring it as 4 or 5 on a Likert scale. Conclusions US definitions of synovitis and its elementary components covering the entire pediatric age range were successfully developed through a Delphi process and validated in a web-based still images exercise. These results provide the basis for the standardized US assessment of synovitis in clinical practice and research

Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in acute lung injury to reduce pulmonary dysfunction (HARP-2) trial : study protocol for a randomized controlled trial

Acute lung injury (ALI) is a common devastating clinical syndrome characterized by life-threatening respiratory failure requiring mechanical ventilation and multiple organ failure. There are in vitro, animal studies and pre-clinical data suggesting that statins may be beneficial in ALI. The Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in Acute lung injury to Reduce Pulmonary dysfunction (HARP-2) trial is a multicenter, prospective, randomized, allocation concealed, double-blind, placebo-controlled clinical trial which aims to test the hypothesis that treatment with simvastatin will improve clinical outcomes in patients with ALI

The expression of monocarboxylate transporters in thyroid carcinoma can be associated with the morphological features of BRAF (V600E) mutation

BRAF (V600E) mutation, usually performed by DNA techniques, is one of the most common diagnostic markers in papillary thyroid carcinoma. Few papers have demonstrated that plump cells (eosinophilic cytoplasms and papillary thyroid carcinoma nuclei) and peculiar sickle-shaped nuclei represent morphological features of BRAF (V600E) on papillary thyroid carcinomas. These features seem to be linked to glycolytic phenotype whereby monocarboxylate transporters 1-4 are hypothesized to have a dominant role as lactate transporters. We investigated the association between these morphological features and monocarboxylate transporters 1 and 4 in 48 cyto-histological samples diagnosed as "positive for malignancy-favoring papillary thyroid carcinoma". These cases were processed with liquid-based cytology and underwent BRAF (V600E) mutational analysis (pyrosequencing) on liquid-based cytology and monocarboxylate transporters immunostaining on histology. The expression of monocarboxylate transporter 1, monocarboxylate transporter 4, glucose trasporter-1 and carbonic anhidrase were scored semi-quantitatively with expression from 0 to 3+ (strong positivity). The 33 mutated and 15 wild type cases showed 100 % cyto-histological concordance. The cytological evaluation revealed plump cells and sickle nuclear shape in 100 % mutated cases. Monocarboxylate transporter 1 yielded 76 % positivity in the mutated cases especially in both the plump cells and sickle-shaped nuclei, whereas the wild types showed 13.3 % positive monocarboxylate transporter 1 (p = 0.00013). Monocarboxylate transporter 4 resulted in 100 % positivity in mutated and 40 % in wild types (p 0.05). This is the first report analyzing the association between monocarboxylate transporter expression and the morphological features of BRAF (V600E) mutated papillary thyroid carcinomas suggesting the possible involvement of lactate in the morphological features.info:eu-repo/semantics/publishedVersio

Mutual information rate and bounds for it

The amount of information exchanged per unit of time between two nodes in a dynamical network or between two data sets is a powerful concept for analysing complex systems. This quantity, known as the mutual information rate (MIR), is calculated from the mutual information, which is rigorously defined only for random systems. Moreover, the definition of mutual information is based on probabilities of significant events. This work offers a simple alternative way to calculate the MIR in dynamical (deterministic) networks or between two data sets (not fully deterministic), and to calculate its upper and lower bounds without having to calculate probabilities, but rather in terms of well known and well defined quantities in dynamical systems. As possible applications of our bounds, we study the relationship between synchronisation and the exchange of information in a system of two coupled maps and in experimental networks of coupled oscillators

Measurement-based quantum control of mechanical motion

Controlling a quantum system based on the observation of its dynamics is inevitably complicated by the backaction of the measurement process. Efficient measurements, however, maximize the amount of information gained per disturbance incurred. Real-time feedback then enables both canceling the measurement's backaction and controlling the evolution of the quantum state. While such measurement-based quantum control has been demonstrated in the clean settings of cavity and circuit quantum electrodynamics, its application to motional degrees of freedom has remained elusive. Here we show measurement-based quantum control of the motion of a millimetre-sized membrane resonator. An optomechanical transducer resolves the zero-point motion of the soft-clamped resonator in a fraction of its millisecond coherence time, with an overall measurement efficiency close to unity. We use this position record to feedback-cool a resonator mode to its quantum ground state (residual thermal occupation n = 0.29 +- 0.03), 9 dB below the quantum backaction limit of sideband cooling, and six orders of magnitude below the equilibrium occupation of its thermal environment. This realizes a long-standing goal in the field, and adds position and momentum to the degrees of freedom amenable to measurement-based quantum control, with potential applications in quantum information processing and gravitational wave detectors.Comment: New version with corrected detection efficiency as determined with a NIST-calibrated photodiode, added references and revised structure. Main conclusions are identical. 41 pages, 18 figure