Miracle-dz/UniFAR-FTUs huggingface dataset:
Representation of microphysical processes in cloud‐resolving models: Spectral (bin) microphysics versus bulk parameterization

Most atmospheric motions of different spatial scales and precipitation are closely related to phase transitions in clouds. The continuously increasing resolution of large‐scale and mesoscale atmospheric models makes it feasible to treat the evolution of individual clouds. The explicit treatment of clouds requires the simulation of cloud microphysics. Two main approaches describing cloud microphysical properties and processes have been developed in the past four and a half decades: bulk microphysics parameterization and spectral (bin) microphysics (SBM). The development and utilization of both represent an important step forward in cloud modeling. This study presents a detailed survey of the physical basis and the applications of both bulk microphysics parameterization and SBM. The results obtained from simulations of a wide range of atmospheric phenomena, from tropical cyclones through Arctic clouds using these two approaches are compared. Advantages and disadvantages, as well as lines of future development for these methods are discussed.
A novel role of macrophage PIST protein in regulating Leishmania major infection

PDZ protein interacting specifically with Tc10 or PIST is a mammalian trans-Golgi resident protein that regulates subcellular sorting of plasma membrane receptors. PIST has recently been found to play an important role in regulating viral pathogenesis. Alteration in PIST expression is linked to the reprogramming of cell surface receptors which is crucial in determining herpes simplex virus1 infection. In this context, PIST is crucial in triggering autophagy via Beclin 1 -PI3KC3 pathway. However, there is complete lack in our knowledge on the role of this protein in any parasitic infection. Leishmania parasites infect their host macrophage cells via phagocytosis and their survival within the parasitophorous compartment has recently been found to be dependent on host autophagy by a yet to be identified mechanism. Using Leishmania major (L. major)-macrophage infection model system we, for the first-time report here that in infected macrophages Golgi resident PIST protein migrates towards the parasite containing compartment. We have also found that PIST associates with Beclin 1, however, not with LC3 within L. major parasite containing compartment of infected macrophages. Further, we performed genetic ablation of PIST by siRNA and observed that knockdown of macrophage PIST in turn helps in parasite replication. Contrary to this, overexpression of PIST in macrophages restricted the multiplication of L. major. Collectively, our study for the first time reveals that PIST is essential in regulating intracellular parasite, L. major infection within macrophage cells. Summary Statement Mammalian PIST protein plays a crucial role in regulating cellular trafficking events. Here, we showed that PIST status is altered within Leishmania major parasite infected macrophages. Further, we confirmed that PIST is essential in restricting parasite growth. Additionally, a potential interacting axis between PIST and Beclin 1 is identified during infection.
The contribution of plant life and growth forms to global gradients of vascular plant diversity

Plant life and growth forms (shortened to ‘plant forms’) represent key functional strategies of plants in relation to their environment and provide important insights into the ecological constraints acting on the distribution of biodiversity. Despite their ecological importance, how the spectra of plant forms contribute to global gradients of plant diversity is unresolved. Using a novel dataset comprising >295,000 species, we quantify the contribution of different plant forms to global gradients of vascular plant diversity. Further, we establish how plant form distributions in different biogeographical regions are associated with contemporary and paleoclimate conditions, environmental heterogeneity, and phylogeny. We find a major shift in representation by woody perennials in tropical latitudes to herb-dominated floras in temperate and boreal regions, following a sharp latitudinal gradient in plant form diversity from the tropics to the poles. We also find significant functional differences between regions, mirroring life and growth form responses to environmental conditions, which is mostly explained by contemporary climate (18-87%), and phylogeny (6-62%), with paleoclimate and heterogeneity playing only a minor role (<23%). This research highlights variation in the importance of different plant forms to diversity gradients worldwide, providing a much-needed quantification for long-standing ideas and concepts structuring plant assemblages.
Cell-Type Specific Connectivity of Whisker-Related Sensory and Motor Cortical Input to Dorsal Striatum

The anterior dorsolateral striatum (DLS) is heavily innervated by convergent excitatory projections from the primary motor (M1) and sensory cortex (S1) and is considered an important site of sensorimotor integration. M1 and S1 corticostriatal synapses have functional differences in the strength of their connections with striatal spiny projection neurons (SPNs) and fast-spiking interneurons (FSIs) in the DLS, and as a result exert an opposing influence on sensory-guided behaviors. In the present study, we tested whether M1 and S1 inputs exhibit differences in the subcellular anatomical distribution onto striatal neurons. We injected adeno-associated viral vectors encoding spaghetti monster fluorescent proteins (sm.FPs) into M1 and S1, and used confocal microscopy to generate 3D reconstructions of corticostriatal inputs to single identified SPNs and FSIs obtained through ex-vivo patch-clamp electrophysiology. We found that SPNs are less innervated by S1 compared to M1, but FSIs receive a similar number of inputs from both M1 and S1. In addition, M1 and S1 inputs were distributed similarly across the proximal, medial, and distal regions of SPNs and FSIs. Notably, clusters of inputs were prevalent in SPNs but not FSIs. Our results suggest that SPNs have stronger functional connectivity to M1 compared to S1 due to a higher density of synaptic inputs. The clustering of M1 and S1 inputs onto SPNs but not FSIs suggest that cortical inputs are integrated through cell-type specific mechanisms and more generally have implications for how sensorimotor integration is performed in the striatum. Significance Statement The dorsolateral striatum (DLS) is a key brain area involved in sensorimotor integration due to its dense innervation by the primary motor (M1) and sensory cortex (S1). However, the quantity and anatomical distribution of these inputs to the striatal cell population has not been well characterized. In this study we demonstrate that corticostriatal projections from M1 and S1 differentially innervate spiny projection neurons (SPNs) and fast-spiking interneurons (FSIs) in the DLS. S1 inputs innervate SPNs less than M1 and are likely to form synaptic clusters in SPNs but not in FSIs. These findings suggest that sensorimotor integration is partly achieved by differences in the synaptic organization of corticostriatal inputs to local striatal microcircuits.
Modelling capture efficiency of single-cell RNA-sequencing data improves inference of transcriptome-wide burst kinetics

Gene expression is characterised by stochastic bursts of transcription that occur at brief and random periods of promoter activity. The kinetics of gene expression burstiness differs across the genome and is dependent on the promoter sequence, among other factors. Single-cell RNA sequencing (scRNA-seq) has made it possible to quantify the cell-to-cell variability in transcription at a global genome-wide level. However, scRNA-seq data is prone to technical variability, including low and variable capture efficiency of transcripts from individual cells. Here, we propose a novel mathematical theory for the observed variability in scRNA-seq data. Our method captures burst kinetics and variability in both cell size and capture efficiency, which allows us to propose several likelihood-based and simulation-based methods for the inference of burst kinetics from scRNA-seq data. Using both synthetic and real data, we show that the simulation-based methods provide an accurate, robust and flexible tool for inferring burst kinetics from scRNA-seq data. In particular, in supervised manner, a simulation-based inference method based on neural networks proves to be accurate and useful in application to both allele and non-allele specific scRNA-seq data.
Ecient Computation with Dedekind Reals

Cauchy’s construction of reals as sequences of rational approximations is the theoretical basis for a number of implementations of exact real numbers, while Dedekind’s construction of reals as cuts has inspired fewer useful computational ideas. Nevertheless, we can see the computational content of Dedekind reals by constructing them within Abstract Stone Duality (ASD), a computationally meaningful calculus for topology. This provides the theoretical background for a novel way of computing with real numbers in the style of logic programming. Real numbers are dened in terms of (lower and upper) Dedekind cuts, while programs are expressed as statements about real numbers in the language of ASD. By adapting Newton’s method to interval arithmetic we can make the computations as ecient as those based on Cauchy reals. The results reported in this talk are joint work with Paul Taylor.
Spontaneous Necker-Cube Reversals are not that Spontaneous

During observation of the ambiguous Necker cube, our perception suddenly reverses between two about equally possible 3D interpretations. During passive observation, perceptual reversals seem to be sudden and spontaneous. A number of theoretical approaches postulate destabilization of neural representations as a precondition for spontaneous reversals of ambiguous figures. In the current study, we focused on possible EEG correlates of perceptual destabilization, that may allow to predict an upcoming perceptual reversal. We presented ambiguous Necker cube stimuli in an onset-paradigm and investigated the neural processes underlying endogenous reversals as compared to perceptual stability across two consecutive stimulus presentations. In a separate experimental condition, disambiguated cube variants were alternated randomly, to exogenously induce perceptual reversals. We compared the EEG immediately before and during endogenous Necker cube reversals with corresponding time windows during exogenously induced perceptual reversals of disambiguated cube variants. For the ambiguous Necker cube stimuli, we found the earliest differences in the EEG between reversal trials and stability trials already one second before a reversal occurred, at bilateral parietal electrodes. The traces remained similar until approximately 1100 ms before a perceived reversal, became maximally different at around 890 ms (p=7.59*10−6, Cohen’s d=1.35) and remained different until shortly before offset of the stimulus preceding the reversal. No such patterns were found in the case of disambiguated cube variants. The identified EEG effects may reflect destabilized states of neural representations, related to destabilized perceptual states preceding a perceptual reversal. They further indicate that spontaneous Necker cube reversals are most probably not as spontaneous as generally thought. Rather, the destabilization may occur over a longer time scale, at least one second before a reversal event.
An innate granuloma eradicates an environmental pathogen using Gsdmd and Nos2

Granulomas often form around pathogens that cause chronic infections. Here, we discover a novel granuloma model in mice. Chromobacterium violaceum is an environmental bacterium that stimulates granuloma formation that not only successfully walls off but also clears the infection. The infected lesion can arise from a single bacterium that replicates in the presence of a neutrophil swarm. Bacterial replication ceases when macrophages organize around the infection and form a granuloma. This granuloma response is accomplished independently of adaptive immunity that is typically required to organize granulomas. The C. violaceum-induced granuloma requires at least two separate defense pathways, gasdermin D and iNOS, to maintain the integrity of the granuloma architecture. These innate granulomas successfully eradicate C. violaceum infection. Therefore, this new C. violaceum-induced granuloma model demonstrates that innate immune cells successfully organize a granuloma and thereby eradicate infection by an environmental pathogen.
The pleiotropic functions of Pri smORF peptides synchronize leg development regulators

The last decade witnesses the emergence of the abundant family of smORF peptides, encoded by small ORF (<100 codons), whose biological functions remain largely unexplored. Bioinformatic analyses here identify hundreds of putative smORF peptides expressed in Drosophila imaginal leg discs. Thanks to a functional screen in legs, we found smORF peptides involved in morphogenesis, including the pioneer smORF peptides Pri. Since we identified its target Ubr3 in the epidermis and pri was known to control leg development through misunderstood mechanisms, we investigated the role of Ubr3 in mediating pri function in legs. We found that pri play several roles during leg development both in patterning and in cell survival. At larval pupal transition, Pri peptides cooperate with Ubr3 to insure cell survival and leg morphogenesis. Earlier, during larval stage, pri activates independently of Ubr3 tarsal transcriptional programs and Notch and EGFR signalling pathways. Our results highlight Ubr3 dependent and independent functions of Pri peptides and their pleiotropy. Moreover, we reveal that the smORF peptide family is a reservoir of overlooked developmental regulators, displaying distinct molecular functions and orchestrating leg development. Summary statement Pri smORF peptides activate multiple actors regulating signalling pathways, transcription and apoptosis by distinct mechanisms to insure tarsal patterning and epithelial morphogenesis during leg development.
Discovery of long non-coding RNAs in the liver fluke, Fasciola hepatica

Long non-coding (lnc)RNAs are a class of eukaryotic RNA that do not code for protein and are linked with transcriptional regulation, amongst a myriad of other functions. Using a custom in silico pipeline we have identified 6,436 putative lncRNA transcripts in the liver fluke parasite, Fasciola hepatica; none of which are conserved with those previously described from Schistosoma mansoni. F. hepatica lncRNAs were distinct from F. hepatica mRNAs in transcript length, coding probability, exon/intron composition, expression patterns, and genome distribution. RNA-Seq and digital droplet PCR measurements demonstrated developmentally regulated expression of lncRNAs between intra-mammalian life stages; a similar proportion of lncRNAs (14.2 %) and mRNAs (12.8 %) were differentially expressed (p<0.001), supporting a functional role for lncRNAs in F. hepatica life stages. While most lncRNAs (81%) were intergenic, we identified some that overlapped protein coding loci in antisense (13%) or intronic (6%) configurations. We found no unequivocal evidence for correlated developmental expression within positionally correlated lncRNA:mRNA pairs, but global co-expression analysis identified five lncRNA that were inversely co-regulated with 89 mRNAs, including a large number of functionally essential proteases. The presence of micro (mi)RNA binding sites in 3135 lncRNAs indicates the potential for miRNA-based post-transcriptional regulation of lncRNA, and/or their function as competing endogenous (ce)RNAs. This first description of lncRNAs in F. hepatica provides an avenue to future functional and comparative genomics studies that will provide a new perspective on a poorly understood aspect of parasite biology.
An improved Nicotiana benthamiana bioproduction chassis provides novel insights into nicotine biosynthesis

The model plant Nicotiana benthamiana is an increasingly attractive organism for the production of high-value, biologically active molecules. However, N. benthamiana accumulates high levels of pyridine alkaloids, in particular nicotine, which complicates the downstream purification processes. Here, we report the assembly of an improved N. benthamiana genome as well as the generation of low-nicotine lines by CRISPR/Cas9-based inactivation of berberine bridge enzyme-like proteins (BBLs). Triple as well as quintuple mutants accumulated 3-4 times less nicotine than the respective control lines. The availability of lines without functional BBLs allowed us to probe their catalytic role in nicotine biosynthesis, which has remained obscure. Notably, chiral analysis revealed that the enantiomeric purity of nicotine was fully lost in the quintuple mutants. In addition, precursor feeding experiments showed that these mutants cannot facilitate the specific loss of C6 hydrogen that characterizes natural nicotine biosynthesis. Our work delivers an improved N. benthamiana chassis for bioproduction and opens the possibility that BBLs are the sought-after coupling enzymes in nicotine biosynthesis.
Localisation and tissue tropism of the symbiont Microsporidia MB in the germ line and somatic tissues of Anopheles arabiensis

The Anopheles symbiont, Microsporidia MB, is maternally inherited and has a strong malaria transmission-blocking phenotype in Anopheles arabiensis. Microsporidia MB is also vertically transmitted, sexually transmitted and avirulent. These characteristics are expected to promote its spread through mosquito populations, enhancing the potential of Microsporidia MB as a candidate for the development of a symbiont-mediated malaria transmission blocking strategy. We found that the patterns of Microsporidia MB localisation over the development of An. arabiensis indicate accumulation in tissues linked to its transmission, specifically the male and female gonadal tissues. Transovarial vertical transmission of Microsporidia MB occurs in the female An. arabiensis ovary when Microsporidia MB becomes localised to the cytoplasm of the developing oocyte. In male An. arabiensis, Microsporidia MB is localised in the testis and vas deferens. Notably, a high intensity of Microsporidia MB can also be observed in the An. arabiensis adult but not larval gut. The levels of Microsporidia MB found in the female ovary are linked to the progression of oogenesis, increasing after blood feeding initiates the development of eggs. The levels of Microsporiodia MB in the male and female gonadal and gut tissue do not increase as mosquitoes age. Altogether, the high specificity of Microsporidia MB tissue localisation patterns and changes in infection prevalence and intensity suggest adaptation to maximise transmission and avirulence in Anopheles arabiensis. Importance Microsporidia MB is a symbiont with strong malaria transmission-blocking phenotype in Anopheles arabiensis. It spreads in mosquito populations through mother-to-offspring and sexual transmission. The ability of Microsporidia MB to block Plasmodium transmission together with its ability to spread within Anopheles populations and its avirulence to the host makes it a very attractive candidate for developing a key strategy to stop malaria transmissions. Here, we report the basis of Microsporidia MB transmission. We find that Microsporidia MB accumulates in Anopheles arabiensis tissues linked to its sexual and vertical transmission. Its prevalence and intensity in the tissues over the mosquito life cycle suggest adaptation to maximise transmission and avirulence in Anopheles arabiensis. These findings provide the foundation for understanding the factors that affect Microsporidia MB transmission efficiency. This will contribute to the establishment of strategies to maximize Microsporidia MB transmission for Anopheles mosquito population replacement and malaria transmission blocking.
Parameterization for the ITER Production

A number of models for the critical surface of , and in general A15 superconductors, have been devel- oped in the past years. This paper compares the most common parameterizations using consistent notation. Although the pa- rameterizations appear dissimilar at first sight, they are in reality all based on a fit of the normalized pinning force vs. the reduced field, and have similar scalings for the critical field and critical temperature based on a Unified Scaling Law. In this paper we take the various parameterizations as a basis for a generic scaling proposed for the characterization and production follow-up of the ITER strands. The accuracy of the scaling is estimated using the fitting residuals on various sets of data available in literature. We discuss the results, and give our view of the work towards a unified, practical parameterization.
Ensemble Generation for Models of Multimodal Systems

Abstract In this work the performance of ensembles generated by commonly used methods in a nonlinear system with multiple attractors is examined. The model used here is a spectral truncation of a barotropic quasigeostrophic channel model. The system studied here has 44 state variables, great enough to exhibit the problems associated with high state dimension, but small enough so that experiments with very large ensembles are practical, and relevant probability density functions (PDFs) can be evaluated explicitly. The attracting sets include two stable limit cycles. To begin, the basins of attraction of two known stable limit cycles are characterized. Large ensembles are then used to calculate the evolution of initially Gaussian PDFs with a range of initial covariances. If the initial covariances are small, the PDF remains essentially unimodal, and the probability that a point drawn from the initial PDF lies in a different basin of attraction from the mean of that PDF is small. If the initial covariances a.
Erzeugende und Relationen verallgemeinerter Einheitengruppen.

Ist R einer der oben genannten Ringe, so sei GR die Gruppe derjenigen Matrizen X aus G, deren Komponenten samt denen der Inversen X^ in R liegen. Es ist bekannt ([2], Thm. 6. 12 und 12.3; [3], §5), daß G0 durch endlich viele Elemente erzeugt und durch endlich viele Relationen definiert werden kann. Dasselbe wurde in [1] im Falle einiger klassischer Gruppen auch für G0(Ä) bewiesen. Andererseits /l x\ ist G0(Ä) schon für die Gruppe G der Matrizen L . l und allgemeiner für alle unipotenten Gruppen nicht mehr endlich erzeugbar. Es erhebt sich die Frage, unter welchen Umständen die Gruppe G0(Ä) endlich erzeugbar bzw. definierbar ist. Im folgenden wird diese Frage auf ähnliche Fragen über die p-adischen Gruppen Gk zurückgeführt. Sagen wir, eine Teilmenge L einer Gruppe H sei ein definierender Teil von H, wenn H von L erzeugt und durch alle zwischen Elementen a, &, c aus L bestehenden Relationen ab = c definiert wird, so gilt nämlich der Satz. Die Gruppe G0(S) ist genau dann durch endlich viele Elemente erzeugbar (bzw. auch durch endlich viele Relationen definierbar), wenn Gk für jedes $$S einen (in der $-adischen Topologie) kompakten erzeugenden (bzw. definierenden) Teil besitzt. Es bleibt also die Frage, welche Gruppen Gk einen kompakten erzeugenden (bzw, definierenden) Teil haben. Hierzu hat A. Borel gezeigt): ) Unveröffentlicht.