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The presence of a mean magnetic field aligned with the direction of the acceleration greatly modifies the development of the Rayleigh–Taylor instability (RTI). High resolution direct numerical simulations of the Boussinesq–Navier–Stokes equations under the magnetohydrodynamics approximation reveal that, after an initial damping of the perturbations at the interface between the two miscible fluids, a rapid increase of the mixing layer is observed. Structures are significantly stretched in the vertical direction because magnetic tension prevents small-scale shear instabilities. When the vertical turbulent velocity exceeds the Alfvén velocity, the flow transitions to turbulence, structures break and an enhanced mixing occurs with strong dissipation. Afterwards, the mixing zone slows down and its growth rate is decreased compared to the hydrodynamic case. For larger magnitudes of the mean magnetic field, a strong anisotropy persists, and an increased fraction of potential energy injected into the system is lost into turbulent magnetic energy: as a consequence, the mixing zone growth rate is decreased even more. This phenomenology is embedded in a general buoyancy-drag equation, derived from simplified equations that reflect the large-scale dynamics, in which the drag coefficient is increased by the presence of turbulent magnetic energy.

The possibility to accelerate electron beams to ultra-relativistic velocities over short distances by using plasma-based technology holds the potential for a revolution in the field of particle accelerators 1 – 4 . The compact nature of plasma-based accelerators would allow the realization of table-top machines capable of driving a free-electron laser (FEL) 5 , a formidable tool to investigate matter at the sub-atomic level by generating coherent light pulses with sub-ångström wavelengths and sub-femtosecond durations 6 , 7 . So far, however, the high-energy electron beams required to operate FELs had to be obtained through the use of conventional large-size radio-frequency (RF) accelerators, bound to a sizeable footprint as a result of their limited accelerating fields. Here we report the experimental evidence of FEL lasing by a compact (3-cm) particle-beam-driven plasma accelerator. The accelerated beams are completely characterized in the six-dimensional phase space and have high quality, comparable with state-of-the-art accelerators 8 . This allowed the observation of narrow-band amplified radiation in the infrared range with typical exponential growth of its intensity over six consecutive undulators. This proof-of-principle experiment represents a fundamental milestone in the use of plasma-based accelerators, contributing to the development of next-generation compact facilities for user-oriented applications 9 . Using a compact, particle-beam-driven plasma-based accelerator to accelerate high-quality electron beams that are completely characterized in the six-dimensional phase space, free-electron lasing  is observed with narrow-band amplified radiation in the infrared range.

Selective inhibition of BCL-2 is expected to enhance therapeutic vulnerability in luminal estrogen receptor-positive breast cancers. We show here that the BCL-2 dependency of luminal tumor cells is nevertheless mitigated by breast cancer-associated fibroblasts (bCAFs) in a manner that defines MCL-1 as another critical therapeutic target. bCAFs favor MCL-1 expression and apoptotic resistance in luminal cancer cells in a IL-6 dependent manner while their own, robust, survival also relies on MCL-1. Studies based on ex vivo cultures of human luminal breast cancer tissues further argue that the contribution of stroma-derived signals to MCL-1 expression shapes BCL-2 dependency. Thus, MCL-1 inhibitors are beneficial for targeted apoptosis of breast tumor ecosystems, even in a subtype where MCL-1 dependency is not intrinsically driven by oncogenic pathways.

Karyotype complexity has major prognostic value in many malignancies. There is no consensus on the definition of a complex karyotype, and the prognostic impact of karyotype complexity differs from one disease to another. Due to the importance of the complex karyotype in the prognosis and treatment of several hematological diseases, the Francophone Group of Hematological Cytogenetics (Groupe Francophone de Cytogénétique Hématologique, GFCH) has developed an up-to-date, practical document for helping cytogeneticists to assess complex karyotypes in these hematological disorders. The evaluation of karyotype complexity is challenging, and it would be useful to have a consensus method for counting the number of chromosomal abnormalities (CAs). Although it is not possible to establish a single prognostic threshold for the number of CAs in all malignancies, a specific consensus prognostic cut-off must be defined for each individual disease. In order to standardize current cytogenetic practices and apply a single denomination, we suggest defining a low complex karyotype as having 3 CAs, an intermediate complex karyotype as having 4 CAs, and a highly complex karyotype as having 5 or more CAs.

Transcription by RNA Polymerase II (Pol II) is initiated by the hierarchical assembly of the pre-initiation complex onto promoter DNA. Decades of research have shown that the TATA-box binding protein (TBP) is essential for Pol II loading and initiation. Here, we report instead that acute depletion of TBP in mouse embryonic stem cells has no global effect on ongoing Pol II transcription. In contrast, acute TBP depletion severely impairs RNA Polymerase III initiation. Furthermore, Pol II transcriptional induction occurs normally upon TBP depletion. This TBP-independent transcription mechanism is not due to a functional redundancy with the TBP paralog TRF2, though TRF2 also binds to promoters of transcribed genes. Rather, we show that the TFIID complex can form and, despite having reduced TAF4 and TFIIA binding when TBP is depleted, the Pol II machinery is sufficiently robust in sustaining TBP-independent transcription.

The Free-Electron Laser facility of the EuPRAXIA@SPARC_LAB infrastructure is driven by an electron beam with 1 GeV energy, produced by an X-band normal conducting linear accelerator followed by a plasma wakefield acceleration stage. The AQUA beamline aims at delivering variable polarization photons in the 3-4 nm wavelength range by means of out-of-vacuum APPLE-X permanent magnet undulators with 18 mm period length. The main radiator is composed by an array of ten APPLE-X 2 m-long modules. The current AQUA design is investigated and discussed taking into account effects on the FEL performance from off-axis injection as well as from modelling of the resistive wall wakefields in the foreseen vacuum chamber.

Despite effective treatment for those living with Human Immunodeficiency Virus (HIV), there are still two million new infections each year. Protein-based HIV entry inhibitors, being highly effective and specific, could be used to protect people from initial infection. One of the most promising of these for clinical use is 5P12-RANTES, a variant of the chemokine RANTES/CCL5. The N-terminal amino acid of 5P12-RANTES is glutamine (Gln; called Q0), a residue that is prone to spontaneous cyclization when at the N-terminus of a protein. It is not known how this cyclization affects the potency of the inhibitor or whether cyclization is necessary for the function of the protein, although the N-terminal region of RANTES has been shown to be critical for receptor interactions, with even small changes having a large effect. We have studied the kinetics of cyclization of 5P12-RANTES as well as N-terminal variations of the protein that either produce an identical cyclized terminus (Glu0) or that cannot similarly cyclize (Asn0, Phe0, Ile0, and Leu0). We find that the half life for N-terminal cyclization of Gln is roughly 20 h at pH 7.3 at 37 °C. However, our results show that cyclization is not necessary for the potency of this protein and that several replacement terminal amino acids produce nearly-equally potent HIV inhibitors while remaining CC chemokine receptor 5 (CCR5) antagonists. This work has ramifications for the production of active 5P12-RANTES for use in the clinic, while also opening the possibility of developing other inhibitors by varying the N-terminus of the protein.

We have designed, fabricated and measured high-Q λ /2 coplanar waveguide microwave resonators whose resonance frequency is made tunable with magnetic field by inserting a DC-SQUID array (including 1 or 7 SQUIDs) inside. Their tunability range is 30% of the zero field frequency. Their quality factor reaches up to 3×10 4 . We present a model based on thermal fluctuations that accounts for the dependence of the quality factor with magnetic field.

ObjectivesThe objective of this study was to evaluate whether higher reported accuracy estimates are associated with shorter time to publication among imaging diagnostic accuracy studies.MethodsWe included primary imaging diagnostic accuracy studies, included in meta-analyses from systematic reviews published in 2015. For each primary study, we extracted accuracy estimates, participant recruitment periods and publication dates. Our primary outcome was the association between Youden’s index (sensitivity + specificity − 1, a single measure of diagnostic accuracy) and time to publication.ResultsWe included 55 systematic reviews and 781 primary studies. Study completion dates were missing for 238 (30%) studies. The median time from completion to publication in the remaining 543 studies was 20 months (IQR 14–29). Youden’s index was negatively correlated with time from completion to publication (rho = −0.11, p = 0.009). This association remained significant in multivariable Cox regression analyses after adjusting for seven study characteristics: hazard ratio of publication was 1.09 (95% CI 1.03–1.16, p = 0.004) per unit increase for logit-transformed estimates of Youden’s index. When dichotomizing Youden’s index by a median split, time from completion to publication was 20 months (IQR 13–33) for studies with a Youden’s index below the median, and 19 months (14–27) for studies with a Youden’s index above the median (p = 0.104).ConclusionImaging diagnostic accuracy studies with higher accuracy estimates were weakly associated with a shorter time to publication.Key points• Higher accuracy estimates are weakly associated with shorter time to publication.• Lag in time to publication remained significant in multivariate Cox regression analyses.• No correlation between accuracy and time from submission to publication was identified.

PurposeTo evaluate the epidemiology of systematic reviews (SRs) published in imaging journals.MethodsA MEDLINE search identified SRs published in imaging journals from 1 January 2000–31 December 2016. Articles retrieved were screened against inclusion criteria. Demographic and methodological characteristics were extracted from studies. Temporal trends were evaluated using linear regression and Pearson’s correlation coefficients.Results921 SRs were included that reported on 27,435 primary studies, 85,276,484 patients and were cited 26,961 times. The SR publication rate increased 23-fold (r=0.92, p<0.001) while the proportion of SRs to non-SRs increased 13-fold (r = 0.94, p<0.001) from 2000 (0.10%) to 2016 (1.33%). Diagnostic test accuracy (DTA) SRs were most frequent (46.5%) followed by therapeutic SRs (16.6%). Most SRs did not report funding status (54.2%). The median author team size was five; this increased over time (r=0.20, p<0.001). Of the studies, 67.3% included an imaging specialist co-author; this decreased over time (r=-0.57, p=0.017). Most SRs included a meta-analysis (69.6%). Journal impact factor positively correlated with SR publication rates (r=0.54, p<0.001). Magnetic resonance imaging (MRI) and ‘vascular and interventional radiology’ were the most frequently studied imaging modality and subspecialty, respectively. The USA, UK, China, Netherlands and Canada were the top five publishing countries.ConclusionsThe SR publication rate is increasing rapidly compared with the rate of growth of non-SRs; however, they still make up just over 1% of all studies. Authors, reviewers and editors should be aware of methodological and reporting standards specific to imaging systematic reviews including those for DTA and individual patient data.Key Points• Systematic review publication rate has increased 23-fold from 2000–2016.• The proportion of systematic reviews to non-systematic reviews has increased 13-fold.• The USA, UK and China are the most frequent published countries; those from the USA and China are increasing the most rapidly.