Saturation of the filament density of ultrashort intense laser pulses in air

We experimentally and numerically characterize multiple filamentation of laser pulses with incident intensities of a few TW/cm2. Propagating 100TW laser pulses over 42m in air, we observe a new propagation regime where the filament density saturates. As also evidenced by numerical simulations in the same intensity range, the total number of filaments is governed by geometric constraints and mutual interactions among filaments rather than by the available power in the bea

The 10th VLTI School of Interferometry: Premiering a Fully Online Format

International audienceVery Large Telescope Inerferometer (VLTI) schools have nearly a 20-year history and have trained a significant fraction of today's optical interferometrists who use high-angular-resolution techniques on a regular basis. Very early in the development of the VLTI, training was identified by the community as a necessary tool, as the expertise in optical long-baseline interferometry was limited to a few groups in France and Germany (in those early years the UK was not an ESO member state). The first VLTI school took place in Les Houches, France, in 2002 and since then VLTI schools have been organised in several locations (France, Germany, Hungary, Poland, Portugal) roughly every two years, the previous one being held in 2018 in Lisbon. The VLTI schools are funded and coordinated through the European Interferometry Initiative (Eii)

The Synovial Sarcoma-Associated SYT-SSX2 Oncogene Antagonizes the Polycomb Complex Protein Bmi1

This study demonstrates deregulation of polycomb activity by the synovial sarcoma-associated SYT-SSX2 oncogene, also known as SS18-SSX2. Synovial sarcoma is a soft tissue cancer associated with a recurrent t(X:18) translocation event that generates one of two fusion proteins, SYT-SSX1 or SYT-SSX2. The role of the translocation products in this disease is poorly understood. We present evidence that the SYT-SSX2 fusion protein interacts with the polycomb repressive complex and modulates its gene silencing activity. SYT-SSX2 causes destabilization of the polycomb subunit Bmi1, resulting in impairment of polycomb-associated histone H2A ubiquitination and reactivation of polycomb target genes. Silencing by polycomb complexes plays a vital role in numerous physiological processes. In recent years, numerous reports have implicated gain of polycomb silencing function in several cancers. This study provides evidence that, in the appropriate context, expression of the SYT-SSX2 oncogene leads to loss of polycomb function. It challenges the notion that cancer is solely associated with an increase in polycomb function and suggests that any imbalance in polycomb activity could drive the cell toward oncogenesis. These findings provide a mechanism by which the SYT-SSX2 chimera may contribute to synovial sarcoma pathogenesis

Dynamic changes in gene expression in vivo predict prognosis of tamoxifen-treated patients with breast cancer

Introduction: Tamoxifen is the most widely prescribed anti-estrogen treatment for patients with estrogen receptor (ER)-positive breast cancer. However, there is still a need for biomarkers that reliably predict endocrine sensitivity in breast cancers and these may well be expressed in a dynamic manner. Methods: In this study we assessed gene expression changes at multiple time points (days 1, 2, 4, 7, 14) after tamoxifen treatment in the ER-positive ZR-75-1 xenograft model that displays significant changes in apoptosis, proliferation and angiogenesis within 2 days of therapy. Results: Hierarchical clustering identified six time-related gene expression patterns, which separated into three groups: two with early/transient responses, two with continuous/late responses and two with variable response patterns. The early/transient response represented reductions in many genes that are involved in cell cycle and proliferation (e.g. BUB1B, CCNA2, CDKN3, MKI67, UBE2C), whereas the continuous/late changed genes represented the more classical estrogen response genes (e.g. TFF1, TFF3, IGFBP5). Genes and the proteins they encode were confirmed to have similar temporal patterns of expression in vitro and in vivo and correlated with reduction in tumour volume in primary breast cancer. The profiles of genes that were most differentially expressed on days 2, 4 and 7 following treatment were able to predict prognosis, whereas those most changed on days 1 and 14 were not, in four tamoxifen treated datasets representing a total of 404 patients. Conclusions: Both early/transient/proliferation response genes and continuous/late/estrogen-response genes are able to predict prognosis of primary breast tumours in a dynamic manner. Temporal expression of therapy-response genes is clearly an important factor in characterising the response to endocrine therapy in breast tumours which has significant implications for the timing of biopsies in neoadjuvant biomarker studies.Publisher PDFPeer reviewe

Renal artery stenosis evaluation: diagnostic performance of gadobenate dimeglumine-enhanced MR angiography--comparison with DSA

PURPOSE: To prospectively determine diagnostic performance and safety of contrast material-enhanced (CE) magnetic resonance (MR) angiography with 0.1 mmol per kilogram of body weight gadobenate dimeglumine for depiction of significant steno-occlusive disease (> or =51% stenosis) of renal arteries, with digital subtraction angiography (DSA) as reference standard. MATERIALS AND METHODS: This multicenter study was approved by local institutional review boards; all patients provided written informed consent. Patient enrollment and examination at centers in the United States complied with HIPAA. Two hundred ninety-three patients (154 men, 139 women; mean age, 61.0 years) with severe hypertension (82.2%), progressive renal failure (11.3%), and suspected renal artery stenosis (6.5%) underwent CE MR angiography with three-dimensional spoiled gradient-echo sequences after administration of 0.1 mmol/kg gadobenate dimeglumine at 2 mL/sec. Anteroposterior and oblique DSA was performed in 268 (91.5%) patients. Three independent blinded reviewers evaluated CE MR angiographic images. Sensitivity, specificity, and accuracy of CE MR angiography for detection of significant steno-occlusive disease (> or =51% vessel lumen narrowing) were determined at segment (main renal artery) and patient levels. Positive and negative predictive values and positive and negative likelihood ratios were determined. Interobserver agreement was analyzed with generalized kappa statistics. A safety evaluation (clinical examination, electrocardiogram, blood and urine analysis, monitoring for adverse events) was performed. RESULTS: Of 268 patients, 178 who were evaluated with MR angiography and DSA had significant steno-occlusive disease of renal arteries at DSA. Sensitivity, specificity, and accuracy of CE MR angiography for detection of 51% or greater stenosis or occlusion were 60.1%-84.1%, 89.4%-94.7%, and 80.4%-86.9%, respectively, at segment level. Similar values were obtained for predictive values and for patient-level analyses. Few CE MR angiographic examinations (1.9%-2.8%) were technically inadequate. Interobserver agreement for detection of significant steno-occlusive disease was good (79.9% agreement; kappa = 0.69). No safety concerns were noted. CONCLUSION: CE MR angiography performed with 0.1 mmol/kg gadobenate dimeglumine, compared with DSA, is safe and provides good sensitivity, specificity, and accuracy for detection of significant renal artery steno-occlusive disease

Science cases for a visible interferometer

High spatial resolution is the key for the understanding various astrophysical phenomena. But even with the future E-ELT, single dish instruments are limited to a spatial resolution of about 4 mas in the visible. For the closest objects within our Galaxy most of the stellar photosphere remains smaller than 1 mas. With the success of long baseline interferometry these limitations were soom overcome. Today low and high resolution interferometric instruments on the VLTI and CHARA offer an immense range of astrophysical studies. Combining more telescopes and moving to visible wavelengths broadens the science cases even more. With the idea of developing strong science cases for a future visible interferometer, we organized a science group around the following topics: pre-main sequence and main sequence stars, fundamental parameters, asteroseismology and classical pulsating stars, evolved stars, massive stars, active galactic nuclei (AGNs) and imaging techniques. A meeting was organized on the 15th and 16th of January, 2015 in Nice with the support of the Action Specific in Haute Resolution Angulaire (ASHRA), the Programme National en Physique Stellaire (PNPS), the Lagrange Laboratory and the Observatoire de la Cote d'Azur, in order to present these cases and to discuss them further for future visible interferometers. This White Paper presents the outcome of the exchanges. This book is dedicated to the memory of our colleague Olivier Chesneau who passed away at the age of 41

Internal fixation treatments for intertrochanteric fracture: A systematic review and meta-Analysis of randomized evidence

The relative effects of internal fixation strategies for intertrochanteric fracture after operation remain uncertain. We conducted a systematic review and meta-Analysis of randomized controlled trials (RCTs) to address this important issue. We searched PubMed, EMBASE and CENTRAL for RCTs that compared different internal fixation implants in patients with intertrochanteric fracture at 6-month follow-up or longer. We ultimately included 43 trials enrolling 6911 patients; most trials were small in sample sizes and events. Their risk of bias was generally unclear due to insufficient reporting. Because of these, no statistically significant differences were present from most of the comparisons across all the outcomes, and no definitive conclusions can be made. However, a number of trials compared two commonly used internal fixation strategies, gamma nail (GN) and sliding hip screw (SHS). There is good evidence suggesting that, compared to SHS, GN may increase the risk of cut out (OR = 1.87, 95% CI, 1.08 to 3.21), re-operation (OR = 1.61, 95% CI, 1.02 to 2.53), intra-operative (OR = 3.14, 95% CI, 1.34 to 7.35) and later fractures (OR = 3.67, 95% CI, 1.37 to 9.83). Future randomized trials or observational studies that are carefully designed and conducted are warranted to establish the effects of alternative internal fixation strategies for intertrochanteric fracture

Identification of target genes for wild type and truncated HMGA2 in mesenchymal stem-like cells

Background The HMGA2 gene, coding for an architectural transcription factor involved in mesenchymal embryogenesis, is frequently deranged by translocation and/or amplification in mesenchymal tumours, generally leading to over-expression of shortened transcripts and a truncated protein. Methods To identify pathways that are affected by sarcoma-associated variants of HMGA2, we have over-expressed wild type and truncated HMGA2 protein in an immortalized mesenchymal stem-like cell (MSC) line, and investigated the localisation of these proteins and their effects on differentiation and gene expression patterns. Results Over-expression of both transgenes blocked adipogenic differentiation of these cells, and microarray analysis revealed clear changes in gene expression patterns, more pronounced for the truncated protein. Most of the genes that showed altered expression in the HMGA2-overexpressing cells fell into the group of NF-κB-target genes, suggesting a central role for HMGA2 in this pathway. Of particular interest was the pronounced up-regulation of SSX1, already implicated in mesenchymal oncogenesis and stem cell functions, only in cells expressing the truncated protein. Furthermore, over-expression of both HMGA2 forms was associated with a strong repression of the epithelial marker CD24, consistent with the reported low level of CD24 in cancer stem cells. Conclusions We conclude that the c-terminal part of HMGA2 has important functions at least in mesenchymal cells, and the changes in gene expression resulting from overexpressing a protein lacking this domain may add to the malignant potential of sarcomas

A dynamical measure of the black hole mass in a quasar 11 billion years ago

Tight relationships exist in the local universe between the central stellar properties of galaxies and the mass of their supermassive black hole. These suggest galaxies and black holes co-evolve, with the main regulation mechanism being energetic feedback from accretion onto the black hole during its quasar phase. A crucial question is how the relationship between black holes and galaxies evolves with time; a key epoch to probe this relationship is at the peaks of star formation and black hole growth 8-12 billion years ago (redshifts 1-3). Here we report a dynamical measurement of the mass of the black hole in a luminous quasar at a redshift of 2, with a look back time of 11 billion years, by spatially resolving the broad line region. We detect a 40 micro-arcsecond (0.31 pc) spatial offset between the red and blue photocenters of the H$\alpha$ line that traces the velocity gradient of a rotating broad line region. The flux and differential phase spectra are well reproduced by a thick, moderately inclined disk of gas clouds within the sphere of influence of a central black hole with a mass of 3.2x10$^{8}$ solar masses. Molecular gas data reveal a dynamical mass for the host galaxy of 6x10$^{11}$ solar masses, which indicates an under-massive black hole accreting at a super-Eddington rate. This suggests a host galaxy that grew faster than the supermassive black hole, indicating a delay between galaxy and black hole formation for some systems.Comment: 5 pages Main text, 8 figures, 2 tables, to be published in Nature, under embargo until 29 January 2024 16:00 (London