Wideband 67-116 GHz cryogenic receiver development for ALMA Band 2

The Atacama Large Millimeter/sub-millimeter Array (ALMA) is already revolutionising our understanding of the Universe. However, ALMA is not yet equipped with all of its originally planned receiver bands, which will allow it to observe over the full range of frequencies from 35-950 GHz accessible through the Earth's atmosphere. In particular Band 2 (67-90 GHz) has not yet been approved for construction. Recent technological developments in cryogenic monolithic microwave integrated circuit (MMIC) high electron mobility transistor (HEMT) amplifier and orthomode transducer (OMT) design provide an opportunity to extend the originally planned on-sky bandwidth, combining ALMA Bands 2 and 3 into one receiver cartridge covering 67-116 GHz. The IF band definition for the ALMA project took place two decades ago, when 8 GHz of on-sky bandwidth per polarisation channel was an ambitious goal. The new receiver design we present here allows the opportunity to expand ALMA's wideband capabilities, anticipating future upgrades across the entire observatory. Expanding ALMA's instantaneous bandwidth is a high priority, and provides a number of observational advantages, including lower noise in continuum observations, the ability to probe larger portions of an astronomical spectrum for, e.g., widely spaced molecular transitions, and the ability to scan efficiently in frequency space to perform surveys where the redshift or chemical complexity of the object is not known a priori. Wider IF bandwidth also reduces uncertainties in calibration and continuum subtraction that might otherwise compromise science objectives. Here we provide an overview of the component development and overall design for this wideband 67-116 GHz cryogenic receiver cartridge, designed to operate from the Band 2 receiver cartridge slot in the current ALMA front end receiver cryostat.Comment: 8 pages, proceedings from the 8th ESA Workshop on Millimetre-Wave Technology and Applications (https://atpi.eventsair.com/QuickEventWebsitePortal/millimetre-wave/mm-wave

Re-emergence of enterovirus D68 in Europe after easing the COVID-19 lockdown, September 2021

We report a rapid increase in enterovirus D68 (EV-D68) infections, with 139 cases reported from eight European countries between 31 July and 14 October 2021. This upsurge is in line with the seasonality of EV-D68 and was presumably stimulated by the widespread reopening after COVID-19 lockdown. Most cases were identified in September, but more are to be expected in the coming months. Reinforcement of clinical awareness, diagnostic capacities and surveillance of EV-D68 is urgently needed in Europe.Peer Reviewe

Toward visualization of nanomachines in their native cellular environment

The cellular nanocosm is made up of numerous types of macromolecular complexes or biological nanomachines. These form functional modules that are organized into complex subcellular networks. Information on the ultra-structure of these nanomachines has mainly been obtained by analyzing isolated structures, using imaging techniques such as X-ray crystallography, NMR, or single particle electron microscopy (EM). Yet there is a strong need to image biological complexes in a native state and within a cellular environment, in order to gain a better understanding of their functions. Emerging methods in EM are now making this goal reachable. Cryo-electron tomography bypasses the need for conventional fixatives, dehydration and stains, so that a close-to-native environment is retained. As this technique is approaching macromolecular resolution, it is possible to create maps of individual macromolecular complexes. X-ray and NMR data can be ‘docked’ or fitted into the lower resolution particle density maps to create a macromolecular atlas of the cell under normal and pathological conditions. The majority of cells, however, are too thick to be imaged in an intact state and therefore methods such as ‘high pressure freezing’ with ‘freeze-substitution followed by room temperature plastic sectioning’ or ‘cryo-sectioning of unperturbed vitreous fully hydrated samples’ have been introduced for electron tomography. Here, we review methodological considerations for visualizing nanomachines in a close-to-physiological, cellular context. EM is in a renaissance, and further innovations and training in this field should be fully supported

Molecular epidemiology and evolutionary trajectory of emerging echovirus 30, Europe

In 2018, an upsurge in echovirus 30 (E30) infections was reported in Europe. We conducted a large-scale epidemiologic and evolutionary study of 1,329 E30 strains collected in 22 countries in Europe during 2016-2018. Most E30 cases affected persons 0-4 years of age (29%) and 25-34 years of age (27%). Sequences were divided into 6 genetic clades (G1-G6). Most (53%) sequences belonged to G1, followed by G6 (23%), G2 (17%), G4 (4%), G3 (0.3%), and G5 (0.2%). Each clade encompassed unique individual recombinant forms; G1 and G4 displayed >= 2 unique recombinant forms. Rapid turnover of new clades and recombinant forms occurred over time. Clades G1 and G6 dominated in 2018, suggesting the E30 upsurge was caused by emergence of 2 distinct clades circulating in Europe. Investigation into the mechanisms behind the rapid turnover of E30 is crucial for clarifying the epidemiology and evolution of these enterovirus infections.Molecular basis of virus replication, viral pathogenesis and antiviral strategie

High cumulative JC virus seroconversion rate during long-term use of natalizumab

Background and purpose John Cunningham virus (JCV) seropositivity is a risk factor for the development of natalizumab‐associated progressive multifocal leukoencephalopathy (PML) in multiple sclerosis (MS) patients. When JCV seronegative patients seroconvert, their risk of developing PML increases. Limited longitudinal data exist about the seroconversion rate amongst natalizumab‐treated relapsing−remitting MS (RRMS) patients. Our objective was to evaluate the seroconversion rate in a large Dutch cohort of natalizumab‐treated RRMS patients. Seroconversion was defined as at least two consecutive seropositive serum samples (or cessation of therapy after a single seropositive sample because of seropositivity) after initial seronegative testing. Methods and results In our study of 179 patients for whom longitudinal blood samples were available over a long period (median 4.2 years), anti‐JCV antibody indices were measured in 933 available samples. Eighty‐six patients (48.0%) tested seronegative initially. Of these 86 seronegative patients, 23 patients (26.7%) seroconverted during follow‐up. The annualized seroconversion rate was 7.1%. Seroconversion occurred between 9 and 90 months (median 43 months) of treatment. The rate of seroconversion was independent of follow‐up duration. No significant increase was seen in the anti‐JCV antibody index in the non‐converting patients during the follow‐up. Conclusion The annualized seroconversion rate of 7.1% in patients using natalizumab, cumulatively leading to more than 25% of seronegative patients becoming seropositive in 4 years, is of clinical relevance and should be taken into account in the risk assessment when considering the start of natalizumab therapy