Loss of NUMB drives aggressive bladder cancer via a RHOA/ROCK/YAP signaling axis.

Advances in bladder cancer (BCa) treatment have been hampered by the lack of predictive biomarkers and targeted therapies. Here, we demonstrate that loss of the tumor suppressor NUMB promotes aggressive bladder tumorigenesis and worsens disease outcomes. Retrospective cohort studies show that NUMB-loss correlates with poor prognosis in post-cystectomy muscle-invasive BCa patients and increased risk of muscle invasion progression in non-muscle invasive BCa patients.

Fully Bayesian Autoencoders with Latent Sparse Gaussian Processes.

We present a fully Bayesian autoencoder model that treats both local latent variables and global decoder parameters in a Bayesian fashion. This approach allows for flexible priors and posterior approximations while keeping the inference costs low. To achieve this, we introduce an amortized MCMC approach by utilizing an implicit stochastic network to learn sampling from the posterior over local latent variables.

Transport and Nonreciprocity in Monitored Quantum Devices: An Exact Study.

We study noninteracting fermionic systems undergoing continuous monitoring and driven by biased reservoirs. Averaging over the measurement outcomes, we derive exact formulas for the particle and heat flows in the system. We show that these currents feature competing elastic and inelastic components, which depend nontrivially on the monitoring strength γ.

Observation of universal Hall response in strongly interacting Fermions.

The Hall effect, which originates from the motion of charged particles in magnetic fields, has deep consequences for the description of materials, extending far beyond condensed matter. Understanding such an effect in interacting systems represents a fundamental challenge, even for small magnetic fields. In this work, we used an atomic quantum simulator in which we tracked the motion of ultracold fermions in two-leg ribbons threaded by artificial magnetic fields.

How Much Is Enough? A Study on Diffusion Times in Score-Based Generative Models.

Score-based diffusion models are a class of generative models whose dynamics is described by stochastic differential equations that map noise into data. While recent works have started to lay down a theoretical foundation for these models, a detailed understanding of the role of the diffusion time is still lacking. Current best practice advocates for a large to ensure that the forward dynamics brings the diffusion sufficiently close to a known and simple noise distribution; however, a smaller value of should be preferred for a better approximation of the score-matching objective and higher computational efficiency.

Strong coupling between a photon and a hole spin in silicon.

Spins in semiconductor quantum dots constitute a promising platform for scalable quantum information processing. Coupling them strongly to the photonic modes of superconducting microwave resonators would enable fast non-demolition readout and long-range, on-chip connectivity, well beyond nearest-neighbour quantum interactions. Here we demonstrate strong coupling between a microwave photon in a superconducting resonator and a hole spin in a silicon-based double quantum dot issued from a foundry-compatible metal-oxide-semiconductor fabrication process.

Aberrant phosphorylation inactivates Numb in breast cancer causing expansion of the stem cell pool.

Asymmetric cell division is a key tumor suppressor mechanism that prevents the uncontrolled expansion of the stem cell (SC) compartment by generating daughter cells with alternative fates: one retains SC identity and enters quiescence and the other becomes a rapidly proliferating and differentiating progenitor. A critical player in this process is Numb, which partitions asymmetrically at SC mitosis and inflicts different proliferative and differentiative fates in the two daughters. Here, we show that asymmetric Numb partitioning per se is insufficient for the proper control of mammary SC dynamics, with differential phosphorylation and functional inactivation of Numb in the two progeny also required.

CDK12 promotes tumorigenesis but induces vulnerability to therapies inhibiting folate one-carbon metabolism in breast cancer.

Cyclin-dependent kinase 12 (CDK12) overexpression is implicated in breast cancer, but whether it has a primary or only a cooperative tumorigenic role is unclear. Here, we show that transgenic CDK12 overexpression in the mouse mammary gland per se is sufficient to drive the emergence of multiple and multifocal tumors, while, in cooperation with known oncogenes, it promotes earlier tumor onset and metastasis. Integrative transcriptomic, metabolomic and functional data reveal that hyperactivation of the serine-glycine-one-carbon network is a metabolic hallmark inherent to CDK12-induced tumorigenesis.

A Scalable Bayesian Sampling Method Based on Stochastic Gradient Descent Isotropization.

Stochastic gradient sg-based algorithms for Markov chain Monte Carlo sampling (sgmcmc) tackle large-scale Bayesian modeling problems by operating on mini-batches and injecting noise on sgsteps. The sampling properties of these algorithms are determined by user choices, such as the covariance of the injected noise and the learning rate, and by problem-specific factors, such as assumptions on the loss landscape and the covariance of sg noise. However, current sgmcmc algorithms applied to popular complex models such as Deep Nets cannot simultaneously satisfy the assumptions on loss landscapes and on the behavior of the covariance of the sg noise, while operating with the practical requirement of non-vanishing learning rates.

Seasonal Variation of Plant Defense Inductor Ellagitannins in Strawberry Leaves under Field Conditions for Phytosanitary Technological Applications.

Many natural compounds can activate the plant immunity, and for this reason, they have attracted special interest in crop disease management. Previously, we isolated from strawberry leaves an ellagitannin (HeT), which elicits plant defense responses. In this research, we investigated bioactive compounds from field-collected strawberry leaves capable of inducing defense responses in against a bacterial pathogen.

Nucleation of Ergodicity by a Single Mobile Impurity in Supercooled Insulators.

We consider a disordered Hubbard model and show that, at sufficiently weak disorder, a single spin-down mobile impurity can thermalize an extensive initially localized system of spin-up particles. Thermalization is enabled by resonant processes that involve correlated hops of the impurity and localized particles. This effect indicates that Anderson localized insulators behave as "supercooled" systems, with mobile impurities acting as ergodic seeds.

Phase-Coherent Dynamics of Quantum Devices with Local Interactions.

This review illustrates how Local Fermi Liquid (LFL) theories describe the strongly correlated and coherent low-energy dynamics of quantum dot devices. This approach consists in an effective elastic scattering theory, accounting exactly for strong correlations. Here, we focus on the mesoscopic capacitor and recent experiments achieving a Coulomb-induced quantum state transfer.

Strawberry fatty acyl glycosides enhance disease protection, have antibiotic activity and stimulate plant growth.

An increasing interest in the development of products of natural origin for crop disease and pest control has emerged in the last decade. Here we introduce a new family of strawberry acyl glycosides (SAGs) formed by a trisaccharide (GalNAc-GalNAc-Glc) and a monounsaturated fatty acid of 6 to 12 carbon atoms linked to the glucose unit. Application of SAGs to Arabidopsis thaliana (hereafter Arabidopsis) plants triggered a transient oxidative burst, callose deposition and defense gene expression, accompanied by increased protection against two phytopathogens, Pseudomonas viridiflava and Botrytis cinerea.

Cereal Circular RNAs (circRNAs): An Overview of the Computational Resources for Identification and Analysis.

Circular RNAs (circRNAs) are a widespread class of endogenous noncoding RNAs and they have been studied in the past few years, implying important biological functions in all kingdoms of life. Recently, circRNAs have been identified in many plant species, including cereal crops, showing differential expression during stress response and developmental programs, which suggests their role in these process. In the following years, it is expected that insights into the functional roles of circRNAs can be used by cereal scientists and molecular breeders with the aim to develop new strategies for crop improvement.

Vanishing Hall Response of Charged Fermions in a Transverse Magnetic Field.

We study the Hall response of two-dimensional lattice systems of charged fermions in a transverse magnetic field, in the ballistic coherent limit. We identify a setup in which this response vanishes over wide regions of parameter space: the "Landauer-Büttiker" setup commonly studied for coherent quantum transport, consisting of a strip contacted to biased ideal reservoirs of charges. We show that this effect does not rely on particle-hole symmetry, and is robust to a variety of perturbations including variations of the transverse magnetic field, chemical potential, and temperature.

Update on Postnatal Corticosteroids to Prevent or Treat Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is a major complication of premature birth that significantly affects mortality and long-term morbidity in numerous immature infants. Corticosteroids are particularly suitable for treating BPD, as lung inflammation is central to its pathogenesis. Corticosteroids have considerable, fast beneficial effects on lung function in premature infants with lung disease, but they are also associated with several serious adverse effects, which may have a detrimental impact on long-term outcome.

Universal Hall Response in Interacting Quantum Systems.

We theoretically study the Hall effect on interacting M-leg ladder systems, comparing different measures and properties of the zero temperature Hall response in the limit of weak magnetic fields. Focusing on SU(M) symmetric interacting bosons and fermions, as relevant for, e.g.

The Genetic Transformation of Sweet Orange (Citrus sinensis L. Osbeck) for Enhanced Resistance to Citrus Canker.

Developing disease resistance is one of the most important components of any plant breeding program. Citrus traditional breeding methods (bud sport selection, crossbreeding, and other breeding channels) are a laborious task and often hampered by long juvenility, a high degree of heterozygosity, polyembryony, self-incompatibility, and abortion of reproductive organs. An interesting alternative to the classical breeding approach is the use of genetic transformation, which provides the means for adding a single agronomic trait to a plant without otherwise altering its phenotype.

Development of PSP1, a Biostimulant Based on the Elicitor AsES for Disease Management in Monocot and Dicot Crops.

In this work, we present a novel biostimulant for sustainable crop disease management, PSP1, based on the plant defense-elicitor AsES, an extracellular protease produced by the strawberry fungal pathogen . Fungal fermentation conditions and downstream processing were determined to maximize extracellular protein production, product stability and a high plant defense-eliciting activity, as monitored by anthracnose resistance in supernatant-treated strawberry plants subsequently infected with a virulent strain of . Fermentation batches were shown to reduce anthracnose development by 30-60% as compared to infected non-treated plants.

Ellagitannin HeT obtained from strawberry leaves is oxidized by bacterial membranes and inhibits the respiratory chain.

Plant secondary metabolism produces a variety of tannins that have a wide range of biological activities, including activation of plant defenses and antimicrobial, anti-inflammatory and antitumoral effects. The ellagitannin HeT (1--galloyl-2,3;4,6-bis-hexahydroxydiphenoyl-β-d-glucopyranose) from strawberry leaves elicits a strong plant defense response, and exhibits antimicrobial activity associated to the inhibition of the oxygen consumption, but its mechanism of action is unknown. In this paper we investigate the influence of HeT on bacterial cell membrane integrity and its effect on respiration.

The ellagitannin HeT induces electrolyte leakage, calcium influx and the accumulation of nitric oxide and hydrogen peroxide in strawberry.

HeT (1-0-galloyl-2,3; 4,6-bis-hexahydroxydiphenoyl-β-D-glucopyranose) is a penta-esterified ellagitannin obtained from strawberry leaves. Previous studies have shown that foliar application of HeT prior to inoculation with a virulent pathogen increases the resistance toward Colletotrichum acutatum in strawberry plants and to Xanthomonas citri subsp. citri in lemon plants.

Statistical inference in mechanistic models: time warping for improved gradient matching.

Inference in mechanistic models of non-linear differential equations is a challenging problem in current computational statistics. Due to the high computational costs of numerically solving the differential equations in every step of an iterative parameter adaptation scheme, approximate methods based on gradient matching have become popular. However, these methods critically depend on the smoothing scheme for function interpolation.

Probabilistic disease progression modeling to characterize diagnostic uncertainty: Application to staging and prediction in Alzheimer's disease.

Disease progression modeling (DPM) of Alzheimer's disease (AD) aims at revealing long term pathological trajectories from short term clinical data. Along with the ability of providing a data-driven description of the natural evolution of the pathology, DPM has the potential of representing a valuable clinical instrument for automatic diagnosis, by explicitly describing the biomarker transition from normal to pathological stages along the disease time axis. In this work we reformulated DPM within a probabilistic setting to quantify the diagnostic uncertainty of individual disease severity in an hypothetical clinical scenario, with respect to missing measurements, biomarkers, and follow-up information.

Inducible expression of Bs2 R gene from Capsicum chacoense in sweet orange (Citrus sinensis L. Osbeck) confers enhanced resistance to citrus canker disease.

Transgenic expression of the pepper Bs2 gene confers resistance to Xanthomonas campestris pv. vesicatoria (Xcv) pathogenic strains which contain the avrBs2 avirulence gene in susceptible pepper and tomato varieties. The avrBs2 gene is highly conserved among members of the Xanthomonas genus, and the avrBs2 of Xcv shares 96% homology with the avrBs2 of Xanthomonas citri subsp.