Upper estimate of martingale dimension for self-similar fractals

We study upper estimates of the martingale dimension $d_m$ of diffusion processes associated with strong local Dirichlet forms. By applying a general strategy to self-similar Dirichlet forms on self-similar fractals, we prove that $d_m=1$ for natural diffusions on post-critically finite self-similar sets and that $d_m$ is dominated by the spectral dimension for the Brownian motion on Sierpinski carpets.Comment: 49 pages, 7 figures; minor revision with adding a referenc

Tachyon Condensation and Black Strings

We show that under certain conditions, closed string tachyon condensation produces a topology changing transition from black strings to Kaluza-Klein "bubbles of nothing." This can occur when the curvature at the horizon is much smaller than the string scale, so the black string is far from the correspondence point when it would make a transition to an excited fundamental string. This provides a dramatic new endpoint to Hawking evaporation. A similar transition occurs for black p-branes, and can be viewed as a nonextremal version of a geometric transition. Applications to AdS black holes and the AdS soliton are also discussed.Comment: 23 pages, 1 figure, v2: references adde

Nontangential limits and Fatou-type theorems on post-critically finite self-similar sets

In this paper we study the boundary limit properties of harmonic functions on $\mathbb R_+\times K$, the solutions $u(t,x)$ to the Poisson equation $$\frac{\partial^2 u}{\partial t^2} + \Delta u = 0,$$ where $K$ is a p.c.f. set and $\Delta$ its Laplacian given by a regular harmonic structure. In particular, we prove the existence of nontangential limits of the corresponding Poisson integrals, and the analogous results of the classical Fatou theorems for bounded and nontangentially bounded harmonic functions.Comment: 22 page

Deletion of dystrophin In-Frame Exon 5 leads to a severe phenotype: Guidance for Exon skipping strategies

Duchenne and Becker muscular dystrophy severity depends upon the nature and location of the DMD gene lesion and generally correlates with the dystrophin open reading frame. However, there are striking exceptions where an in-frame genomic deletion leads to severe pathology or protein-truncating mutations (nonsense or frame-shifting indels) manifest as mild disease. Exceptions to the dystrophin reading frame rule are usually resolved after molecular diagnosis on muscle RNA. We report a moderate/severe Becker muscular dystrophy patient with an in-frame genomic deletion of DMD exon 5. This mutation has been reported by others as resulting in Duchenne or Intermediate muscular dystrophy, and the loss of this in-frame exon in one patient led to multiple splicing events, including omission of exon 6, that disrupts the open reading frame and is consistent with a severe phenotype. The patient described has a deletion of dystrophin exon 5 that does not compromise recognition of exon 6, and although the deletion does not disrupt the reading frame, his clinical presentation is more severe than would be expected for classical Becker muscular dystrophy. We suggest that the dystrophin isoform lacking the actin-binding sequence encoded by exon 5 is compromised, reflected by the phenotype resulting from induction of this dystrophin isoform in mouse muscle in vivo. Hence, exon skipping to address DMD-causing mutations within DMD exon 5 may not yield an isoform that confers marked clinical benefit. Additional studies will be required to determine whether multi-exon skipping strategies could yield more functional dystrophin isoforms, since some BMD patients with larger in-frame deletions in this region have been reported with mild phenotypes

Impacts and effects of ocean warming on intertidal rocky habitats.

• Intertidal rocky habitats comprise over 50% of the shorelines of the world, supporting a diversity of marine life and providing extensive ecosystem services worth in the region of US$ 5-10 trillion per year. • They are valuable indicators of the impacts of climate change on the wider marine environment and ecosystems. • Changes in species distributions, abundance and phenology have already been observed around the world in response to recent rapid climate change. • Species-level responses will have considerable ramifications for the structure of communities and trophic interactions, leading to eventual changes in ecosystem functioning (e.g. less primary producing canopy-forming algae in the North-east Atlantic). • Whilst progress is made on the mitigation1 required to achieve goals of a lower-carbon world, much can be done to enhance resilience to climate change. Managing the multitude of other interactive impacts on the marine environment, over which society has greater potential control (e.g. overfishing, invasive non-native species, coastal development, and pollution), will enable adaptation1 in the short and medium term of the next 5-50 years

Critical ace2 determinants of sars-cov-2 and group 2b coronavirus infection and replication

The angiotensin-converting enzyme 2 (ACE2) receptor is a major severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) host range determinant, and understanding SARS-CoV-2-ACE2 interactions will provide important insights into COVID-19 pathogenesis and animal model development. SARS-CoV-2 cannot infect mice due to incompatibility between its receptor binding domain and the murine ACE2 receptor. Through molecular modeling and empirical in vitro validation, we identified 5 key amino acid differences between murine and human ACE2 that mediate SARS-CoV-2 infection, generating a chimeric humanized murine ACE2. Additionally, we examined the ability of the humanized murine ACE2 receptor to permit infection by an additional preemergent group 2B coronavirus, WIV-1, providing evidence for the potential pan-virus capabilities of this chimeric receptor. Finally, we predicted the ability of these determinants to inform host range identification of preemergent coronaviruses by evaluating hot spot contacts between SARS-CoV-2 and additional potential host receptors. Our results identify residue determinants that mediate coronavirus receptor usage and host range for application in SARS-CoV-2 and emerging coronavirus animal model development. IMPORTANCE SARS-CoV-2 (the causative agent of COVID-19) is a major public health threat and one of two related coronaviruses that have caused epidemics in modern history. A method of screening potential infectible hosts for preemergent and future emergent coronaviruses would aid in mounting rapid response and intervention strategies during future emergence events. Here, we evaluated determinants of SARS-CoV-2 receptor interactions, identifying key changes that enable or prevent infection. The analysis detailed in this study will aid in the development of model systems to screen emergent coronaviruses as well as treatments to counteract infections

Harmonizing methods to account for soil nitrous oxide emissions in Life Cycle Assessment of agricultural systems

CONTEXT: Worldwide greenhouse gas emissions (GHG) reached 59 Gt of COeq in 2019 and agricultural soils are the primary source of NO emissions. Life cycle assessments (LCA) have been successful in assessing GHG from agricultural systems. However, no review and harmonization attempt has been focused on soil NO emissions, despite the need to improve LCA methodologies for assessing GHG in agricultural LCA. OBJECTIVE: We therefore undertook a review and harmonization of existing methods to account for soil NO emissions in LCA of agricultural systems and products: i) to compare current methods used in LCA; ii) to identify advantages and iii) disadvantages of each method in LCA; iv) to suggest recommendations for LCA of agricultural systems; v) to identify research needs and potential methodological developments to account for soil NO emissions in the LCA of agricultural systems. In this paper, we consider as soil NO emissions, those originated from soils in relation to fertilisers (organic and manufactured), crop residues, land use/land management change, grassland management, manure and slurry applications and from grazing animals. METHODS: The approach adopted was based on two anonymous expert surveys and a series of expert workshops (n = 21) to define general and specific criteria to review LCA methods for GHG emissions used in LCA of agricultural systems. A broad list of keywords and search criteria was used as the research involved GHG assessment in agricultural LCA. Reviewed papers and methodology were then assessed by LCA and soil NO emission experts (n = 14). RESULTS AND DISCUSSION: >25,000 scientific papers and reports were identified, 1175 were screened, 263 included in the final review and 31 scientific papers were related to soil NO emissions. The results showed that a high level of accuracy corresponded to a low level of applicability and vice versa, following the assessment framework developed in this work through participatory approaches. SIGNIFICANCE: The choice of LCA methods, critical for high quality LCA of agricultural systems, should be based on the assessment objectives, data availability and expertise of the LCA practitioner. However, it is preferable to use DNDC model after calibration and validation or direct field measurements, considering system effects. When necessary data are lacking, IPCC tier 2 methodology where available should be used, otherwise 2019 IPCC Tier 1 methodology. This LCA method development should be synchronous with improvements of quantification methods and the assessment of a wider range of agricultural management practices and systems.This research has been developed within the PATHWAYS project, funded by the European Union’s Horizon 2020 Research and Innovation Programme European Union through Horizon 2020 Research and Innovation Programme under grant agreement No 101000395

Characterising splicing defects of ABCA4 variants within exons 13–50 in patient-derived fibroblasts

The ATP-binding cassette subfamily A member 4 gene (ABCA4)-associated retinopathy, Stargardt disease, is the most common monogenic inherited retinal disease. Given the pathogenicity of numerous ABCA4 variants is yet to be examined and a significant proportion (more than 15%) of ABCA4 variants are categorized as splice variants in silico, we therefore established a fibroblast-based splice assay to analyze ABCA4 variants in an Australian Stargardt disease cohort and characterize the pathogenic mechanisms of ABCA4 variants. A cohort of 67 patients clinically diagnosed with Stargardt disease was recruited. Genomic DNA was analysed using a commercial panel for ABCA4 variant detection and the consequences of ABCA4 variants were predicted in silico. Dermal fibroblasts were propagated from skin biopsies, total RNA was extracted and the ABCA4 transcript was amplified by RT-PCR. Our analysis identified a total of 67 unique alleles carrying 74 unique variants. The most prevalent splice-affecting complex allele c.[5461-10T > C; 5603A > T] was carried by 10% of patients in a compound heterozygous state. ABCA4 transcripts from exon 13 to exon 50 were readily detected in fibroblasts. In this region, aberrant splicing was evident in 10 out of 57 variant transcripts (18%), carried by 19 patients (28%). Patient-derived fibroblasts provide a feasible platform for identification of ABCA4 splice variants located within exons 13–50. Experimental evidence of aberrant splicing contributes to the pathogenic classification for ABCA4 variants. Moreover, identification of variants that affect splicing processes provides opportunities for intervention, in particular antisense oligonucleotide-mediated splice correction

Entropy Crisis, Ideal Glass Transition and Polymer Melting: Exact Solution on a Husimi Cactus

We introduce an extension of the lattice model of melting of semiflexible polymers originally proposed by Flory. Along with a bending penalty, present in the original model and involving three sites of the lattice, we introduce an interaction energy that corresponds to the presence of a pair of parallel bonds and a second interaction energy associated with the presence of a hairpin turn. Both these new terms represent four-site interactions. The model is solved exactly on a Husimi cactus, which approximates a square lattice. We study the phase diagram of the system as a function of the energies. For a proper choice of the interaction energies, the model exhibits a first-order melting transition between a liquid and a crystalline phase. The continuation of the liquid phase below this temperature gives rise to a supercooled liquid, which turns continuously into a new low-temperature phase, called metastable liquid. This liquid-liquid transition seems to have some features that are characteristic of the critical transition predicted by the mode-coupling theory.Comment: To be published in Physical Review E, 68 (2) (2003