Learning Fourier-Constrained Diffusion Bridges for MRI Reconstruction

Recent years have witnessed a surge in deep generative models for accelerated MRI reconstruction. Diffusion priors in particular have gained traction with their superior representational fidelity and diversity. Instead of the target transformation from undersampled to fully-sampled data, common diffusion priors are trained to learn a multi-step transformation from Gaussian noise onto fully-sampled data. During inference, data-fidelity projections are injected in between reverse diffusion steps to reach a compromise solution within the span of both the diffusion prior and the imaging operator. Unfortunately, suboptimal solutions can arise as the normality assumption of the diffusion prior causes divergence between learned and target transformations. To address this limitation, here we introduce the first diffusion bridge for accelerated MRI reconstruction. The proposed Fourier-constrained diffusion bridge (FDB) leverages a generalized process to transform between undersampled and fully-sampled data via random noise addition and random frequency removal as degradation operators. Unlike common diffusion priors that use an asymptotic endpoint based on Gaussian noise, FDB captures a transformation between finite endpoints where the initial endpoint is based on moderate degradation of fully-sampled data. Demonstrations on brain MRI indicate that FDB outperforms state-of-the-art reconstruction methods including conventional diffusion priors

Precision calculation of γd→π+nn\gamma d\to \pi^+ nn within chiral perturbation theory

The reaction $\gamma d\to \pi^+ nn$ is calculated up to order $\chi^{5/2}$ in chiral perturbation theory, where $\chi$ denotes the ratio of the pion to the nucleon mass. Special emphasis is put on the role of nucleon--recoil corrections that are the source of contributions with fractional power in $\chi$. Using the known near threshold production amplitude for $\gamma p\to \pi^+ n$ as the only input, the total cross section for $\gamma d\to \pi^+ nn$ is described very well. A conservative estimate suggests that the theoretical uncertainty for the transition operator amounts to 3 % for the computed amplitude near threshold.Comment: 28 page

Chiral Perturbation Theory in Few-Nucleon Systems

The low-energy effective theory of nuclear physics based on chiral symmetry is reviewed. Topics discussed include the nucleon-nucleon force, few-body potentials, isospin violation, pion-deuteron scattering, proton-neutron radiative capture, pion photoproduction on the deuteron, and pion production in proton-proton collisions.Comment: 15 pages, 2 figures, Latex, aipproc.sty and epsfig, invited talk at the 6th Conference on the Intersections of Particle and Nuclear Physics, Big Sky, May 199

Carrying out a multi-model integrated assessment of European energy transition pathways: Challenges and benefits

With the publication of the European Green Deal, the European Union has committed to reaching carbon neutrality by 2050. The envisaged reductions of direct greenhouse gases emissions are seen as technically feasible, but if a wrong path is pursued, significant unintended impacts across borders, sectors, societies and ecosystems may follow. Without the insights gained from an impact assessment framework reaching beyond the techno-economic perspective, the pursuit of direct emission reductions may lead to counterproductive outcomes in the long run. We discuss the opportunities and challenges related to the creation and use of an integrated assessment framework built to inform the European Commission on the path to decarbonisation. The framework is peculiar in that it goes beyond existing ones in its scope, depth and cross-scale coverage, by use of numerous specialised models and case studies. We find challenges of consistency that can be overcome by linking modelling tools iteratively in some cases, harmonising modelling assumptions in others, comparing model outputs in others. We find the highest added value of the framework in additional insights it provides on the technical feasibility of decarbonisation pathways, on vulnerability aspects and on unintended environmental and health impacts on national and sub-national scale.(c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Molecular, genetic and epigenetic pathways of peroxynitrite-induced cellular toxicity

Oxidative stress plays a key role in the pathogenesis of cancer and many metabolic diseases; therefore, an effective antioxidant therapy would be of great importance in these circumstances. Nevertheless, convincing randomized clinical trials revealed that antioxidant supplementations were not associated with significant reduction in incidence of cancer, chronic diseases and all-cause mortality. As oxidation of essential molecules continues, it turns to nitro-oxidative stress because of the involvement of nitric oxide in pathogenesis processes. Peroxynitrite damages via several distinctive mechanisms; first, it has direct toxic effects on all biomolecules and causes lipid peroxidation, protein oxidation and DNA damage. The second mechanism involves the induction of several transcription factors leading to cytokine-induced chronic inflammation. Finally, it causes epigenetic perturbations that exaggerate nuclear factor kappa-B mediated inflammatory gene expression. Lessons-learned from the treatment of several chronic disorders including pulmonary diseases suggest that, chronic inflammation and glucocorticoid resistance are regulated by prolonged peroxynitrite production

Histone Deacetylases Regulate Gonadotropin-Releasing Hormone I Gene Expression via Modulating Otx2-Driven Transcriptional Activity

BACKGROUND: Precise coordination of the hypothalamic-pituitary-gonadal axis orchestrates the normal reproductive function. As a central regulator, the appropriate synthesis and secretion of gonadotropin-releasing hormone I (GnRH-I) from the hypothalamus is essential for the coordination. Recently, emerging evidence indicates that histone deacetylases (HDACs) play an important role in maintaining normal reproductive function. In this study, we identify the potential effects of HDACs on Gnrh1 gene transcription. METHODOLOGY/PRINCIPAL FINDINGS: Inhibition of HDACs activities by trichostatin A (TSA) and valproic acid (VPA) promptly and dramatically repressed transcription of Gnrh1 gene in the mouse immortalized mature GnRH neuronal cells GT1-7. The suppression was connected with a specific region of Gnrh1 gene promoter, which contains two consensus Otx2 binding sites. Otx2 has been known to activate the basal and also enhancer-driven transcription of Gnrh1 gene. The transcriptional activity of Otx2 is negatively modulated by Grg4, a member of the Groucho-related-gene (Grg) family. In the present study, the expression of Otx2 was downregulated by TSA and VPA in GT1-7 cells, accompanied with the opposite changes of Grg4 expression. Chromatin immunoprecipitation and electrophoretic mobility shift assays demonstrated that the DNA-binding activity of Otx2 to Gnrh1 gene was suppressed by TSA and VPA. Overexpression of Otx2 partly abolished the TSA- and VPA-induced downregulation of Gnrh1 gene expression. CONCLUSIONS/SIGNIFICANCE: Our data indicate that HDAC inhibitors downregulate Gnrh1 gene expression via repressing Otx2-driven transcriptional activity. This study should provide an insight for our understanding on the effects of HDACs in the reproductive system and suggests that HDACs could be potential novel targets for the therapy of GnRH-related diseases

Circadian Desynchrony Promotes Metabolic Disruption in a Mouse Model of Shiftwork

Shiftwork is associated with adverse metabolic pathophysiology, and the rising incidence of shiftwork in modern societies is thought to contribute to the worldwide increase in obesity and metabolic syndrome. The underlying mechanisms are largely unknown, but may involve direct physiological effects of nocturnal light exposure, or indirect consequences of perturbed endogenous circadian clocks. This study employs a two-week paradigm in mice to model the early molecular and physiological effects of shiftwork. Two weeks of timed sleep restriction has moderate effects on diurnal activity patterns, feeding behavior, and clock gene regulation in the circadian pacemaker of the suprachiasmatic nucleus. In contrast, microarray analyses reveal global disruption of diurnal liver transcriptome rhythms, enriched for pathways involved in glucose and lipid metabolism and correlating with first indications of altered metabolism. Although altered food timing itself is not sufficient to provoke these effects, stabilizing peripheral clocks by timed food access can restore molecular rhythms and metabolic function under sleep restriction conditions. This study suggests that peripheral circadian desynchrony marks an early event in the metabolic disruption associated with chronic shiftwork. Thus, strengthening the peripheral circadian system by minimizing food intake during night shifts may counteract the adverse physiological consequences frequently observed in human shift workers