G band atmospheric radars: new frontiers in cloud physics

Clouds and associated precipitation are the largest source of uncertainty in current weather and future climate simulations. Observations of the microphysical, dynamical and radiative processes that act at cloud scales are needed to improve our understanding of clouds. The rapid expansion of ground-based super-sites and the availability of continuous profiling and scanning multi-frequency radar observations at 35 and 94 GHz have significantly improved our ability to probe the internal structure of clouds in high temporal-spatial resolution, and to retrieve quantitative cloud and precipitation properties. However, there are still gaps in our ability to probe clouds due to large uncertainties in the retrievals. The present work discusses the potential of G band (frequency between 110 and 300 GHz) Doppler radars in combination with lower frequencies to further improve the retrievals of microphysical properties. Our results show that, thanks to a larger dynamic range in dual-wavelength reflectivity, dual-wavelength attenuation and dual-wavelength Doppler velocity (with respect to a Rayleigh reference), the inclusion of frequencies in the G band can significantly improve current profiling capabilities in three key areas: boundary layer clouds, cirrus and mid-level ice clouds, and precipitating snow

Proteomic mapping of differentially vulnerable pre-synaptic populations identifies regulators of neuronal stability in vivo.

Synapses are an early pathological target in many neurodegenerative diseases ranging from well-known adult onset conditions such as Alzheimer and Parkinson disease to neurodegenerative conditions of childhood such as spinal muscular atrophy (SMA) and neuronal ceroid lipofuscinosis (NCLs). However, the reasons why synapses are particularly vulnerable to such a broad range of neurodegeneration inducing stimuli remains unknown. To identify molecular modulators of synaptic stability and degeneration, we have used the Cln3-/- 33 mouse model of a juvenile form of NCL. We profiled and compared the molecular composition of anatomically-distinct, differentially-affected pre-synaptic populations from the Cln3-/- 35 mouse brain using proteomics followed by bioinformatic analyses. Identified protein candidates were then tested using a Drosophila CLN3 model to study their ability to modify the CLN3-neurodegenerative phenotype in vivo. We identified differential perturbations in a range of molecular cascades correlating with synaptic vulnerability, including valine catabolism and rho signalling pathways. Genetic and pharmacological targeting of key ‘hub’ proteins in such pathways was sufficient to modulate phenotypic presentation in a Drosophila CLN3 model. We propose that such a workflow provides a target rich method for the identification of novel disease regulators which could be applicable to the study of other conditions where appropriate models exist

A new large animal model of CLN5 neuronal ceroid lipofuscinosis in Borderdale sheep is caused by a nucleotide substitution at a consensus splice site (c.571 + 1G >>> A) leading to excision of exon 3

Batten disease (neuronal ceroid lipofuscinoses, NCLs) are a group of inherited childhood diseases that result in severe brain atrophy, blindness and seizures, leading to premature death. To date, eight different genes have been identified, each associated with a different form. Linkage analysis indicated a CLN5 form in a colony of affected New Zealand Borderdale sheep. Sequencing studies established the disease-causing mutation to be a substitution at a consensus splice site (c.571 + 1G > A), leading to the excision of exon 3 and a truncated putative protein. A molecular diagnostic test has been developed based on the excision of exon 3. Sequence alignments support the gene product being a soluble lysosomal protein. Western blotting of isolated storage bodies indicates the specific storage of subunit c of mitochondrial ATP synthase. This flock is being expanded as a large animal model for mechanistic studies and trial therapies

Ihomelanooman onkologinen hoito päivittyi

Tiivistelmä Suomen Melanoomaryhmä ry päivitti suosituksensa ihomelanooman onkologisesta hoidosta. Vuoden kestävää liitännäislääkehoitoa PD-1-vasta-aineella eli immuuniaktivaation vapauttajalla (nivolumabi tai pembrolitsumabi) tai dabrafenibilla ja trametinibilla harkitaan leikatuille, levinneisyysasteen IIIB-IV melanoomapotilaille melanooman uusiutumisriskin pienentämiseksi. Päätös liitännäishoidosta tehdään yhdessä potilaan kanssa hyödyt ja haitat huomioiden. Levinneen melanooman ensilinjan hoitovaihtoehtona ovat PD-1-vasta-aineet, joiden lisäksi BRAFV600-mutaatiopositiivisille potilaille soveltuvat hoidot BRAF:n ja MEK:n estäjillä. Immunologista yhdistelmähoitoa CTLA-4- ja PD-1-vasta-aineilla (ipilimumabi ja nivolumabi) harkitaan huonoennusteisille hyväkuntoisille potilaille. Muita edenneen melanooman lääkehoitovaihtoehtoja ovat onkolyyttinen virushoito (TVEC) pinnallisen metastasoinnin ja isoloitu raajaperfuusio- eli ILP-hoito raajaan rajoittuvan metastasoinnin yhteydessä sekä solunsalpaajahoidot. Nopeasti kehittyvän hoidon vuoksi melanoomapotilaat pyritään rekrytoimaan kliinisiin hoitotutkimuksiin aina kun se on mahdollista