Fractional differentiability for solutions of nonlinear elliptic equations

We study nonlinear elliptic equations in divergence form $${\operatorname{div}}{\mathcal A}(x,Du)={\operatorname{div}}G.$$ When ${\mathcal A}$ has linear growth in $Du$, and assuming that $x\mapsto{\mathcal A}(x,\xi)$ enjoys $B^\alpha_{\frac{n}\alpha, q}$ smoothness, local well-posedness is found in $B^\alpha_{p,q}$ for certain values of $p\in[2,\frac{n}{\alpha})$ and $q\in[1,\infty]$. In the particular case ${\mathcal A}(x,\xi)=A(x)\xi$, $G=0$ and $A\in B^\alpha_{\frac{n}\alpha,q}$, $1\leq q\leq\infty$, we obtain $Du\in B^\alpha_{p,q}$ for each $p<\frac{n}\alpha$. Our main tool in the proof is a more general result, that holds also if ${\mathcal A}$ has growth $s-1$ in $Du$, $2\leq s\leq n$, and asserts local well-posedness in $L^q$ for each $q>s$, provided that $x\mapsto{\mathcal A}(x,\xi)$ satisfies a locally uniform $VMO$ condition

Dike intrusions during rifting episodes obey scaling relationships similar to earthquakes

As continental rifts evolve towards mid-ocean ridges, strain is accommodated by repeated episodes of faulting and magmatism. Discrete rifting episodes have been observed along two subaerial divergent plate boundaries, the Krafla segment of the Northern Volcanic Rift Zone in Iceland and the Manda-Hararo segment of the Red Sea Rift in Ethiopia. In both cases, the initial and largest dike intrusion was followed by a series of smaller intrusions. By performing a statistical analysis of these rifting episodes, we demonstrate that dike intrusions obey scaling relationships similar to earthquakes. We find that the dimensions of dike intrusions obey a power law analogous to the Gutenberg-Richter relation and the long-term release of geodetic moment is governed by a relationship consistent with the Omori law. Due to the effects of magma supply, the timing of secondary dike intrusions differs from that of the aftershocks. This work provides evidence of self-similarity in the rifting process

Tissue Barriers to Arbovirus Infection in Mosquitoes

Citation: Franz, A. W. E., Kantor, A. M., Passarelli, A. L., & Clem, R. J. (2015). Tissue Barriers to Arbovirus Infection in Mosquitoes. Viruses-Basel, 7(7), 3741-3767. doi:10.3390/v7072795Arthropod-borne viruses (arboviruses) circulate in nature between arthropod vectors and vertebrate hosts. Arboviruses often cause devastating diseases in vertebrate hosts, but they typically do not cause significant pathology in their arthropod vectors. Following oral acquisition of a viremic bloodmeal from a vertebrate host, the arbovirus disease cycle requires replication in the cellular environment of the arthropod vector. Once the vector has become systemically and persistently infected, the vector is able to transmit the virus to an uninfected vertebrate host. In order to systemically infect the vector, the virus must cope with innate immune responses and overcome several tissue barriers associated with the midgut and the salivary glands. In this review we describe, in detail, the typical arbovirus infection route in competent mosquito vectors. Based on what is known from the literature, we explain the nature of the tissue barriers that arboviruses are confronted with in a mosquito vector and how arboviruses might surmount these barriers. We also point out controversial findings to highlight particular areas that are not well understood and require further research efforts

Heritable CRISPR/Cas9-Mediated Genome Editing in the Yellow Fever Mosquito, Aedes aegypti

Citation: Dong, S. Z., Lin, J. Y., Held, N. L., Clem, R. J., Passarelli, A. L., & Franz, A. W. E. (2015). Heritable CRISPR/Cas9-Mediated Genome Editing in the Yellow Fever Mosquito, Aedes aegypti. Plos One, 10(3), 13. doi:10.1371/journal.pone.0122353In vivo targeted gene disruption is a powerful tool to study gene function. Thus far, two tools for genome editing in Aedes aegypti have been applied, zinc-finger nucleases (ZFN) and transcription activator-like effector nucleases (TALEN). As a promising alternative to ZFN and TALEN, which are difficult to produce and validate using standard molecular biological techniques, the clustered regularly interspaced short palindromic repeats/CRISPR-associated sequence 9 (CRISPR/Cas9) system has recently been discovered as a "do-it-yourself" genome editing tool. Here, we describe the use of CRISPR/Cas9 in the mosquito vector, Aedes aegypti. In a transgenic mosquito line expressing both Dsred and enhanced cyan fluorescent protein (ECFP) from the eye tissue-specific 3xP3 promoter in separated but tightly linked expression cassettes, we targeted the ECFP nucleotide sequence for disruption. When supplying the Cas9 enzyme and two sgRNAs targeting different regions of the ECFP gene as in vitro transcribed mRNAs for germline transformation, we recovered four different G1 pools (5.5% knockout efficiency) where individuals still expressed DsRed but no longer ECFP. PCR amplification, cloning, and sequencing of PCR amplicons revealed indels in the ECFP target gene ranging from 2-27 nucleotides. These results show for the first time that CRISPR/Cas9 mediated gene editing is achievable in Ae. aegypti, paving the way for further functional genomics related studies in this mosquito species

Long-term clinical and radiographic analysis of platform matching and platform switching implants in the esthetic zone: a retrospective cohort study

Background: The aims of this study are to retrospectively compare the clinical, radiographic and esthetic outcomes of platform switching (PS) and platform matching (PM) dental implants in the anterior maxilla after ≥ 10 years of functional loading. Methods: Marginal bone loss (MBL) levels were recorded; furthermore, peri-implant clinical parameters (PPD, BOP, PI) were collected and the Pink and White Esthetic scores (PES/WES) were used to evaluate the esthetic outcomes. Wilcoxon signed rank tests were performed to compare collected parameters among the two groups, with a p-value &lt; 0.05. Results: A final sample of 58 patients was enrolled in this study (PM implants = 29; PS implants = 29). PS implants showed lower MBL levels (1.02 ± 0.81 mm vs. 1.67 ± 0.99 mm, p = 0.028) and PPD values (3.69 ± 1.1 vs. 5.16 ± 1.09 mm, p &lt; 0.001) compared to PM implants. Mean PES values were higher in the PS group compared to the PM group (8.46 ± 0.69 vs. 7.89 ± 0.78, p &lt; 0.005), while there were no differences for WES values (7.82 ± 1.09 vs. 7.71 ± 0.85, p &gt; 0.05) and peri-implant diseases’ prevalence (p &gt; 0.05). Conclusions: After 10 years, PS implants showed statistically significant lower MBL and PPD values and higher PES values compared to PM implants

Single-cell analysis: visualizing pharmaceutical and metabolite uptake in cells with label-free 3D mass spectrometry imaging

Detecting metabolites and parent compound within a cell type is now a priority for pharmaceutical development. In this context, three-dimensional secondary ion mass spectrometry (SIMS) imaging was used to investigate the cellular uptake of the antiarrhythmic agent amiodarone, a phospholipidosis-inducing pharmaceutical compound. The high lateral resolution and 3D imaging capabilities of SIMS combined with the multiplex capabilities of ToF mass spectrometric detection allows for the visualization of pharmaceutical compound and metabolites in single cells. The intact, unlabeled drug compound was successfully detected at therapeutic dosages in macrophages (cell line: NR8383). Chemical information from endogenous biomolecules was used to correlate drug distributions with morphological features. From this spatial analysis, amiodarone was detected throughout the cell with the majority of the compound found in the membrane and subsurface regions and absent in the nuclear regions. Similar results were obtained when the macrophages were doped with amiodarone metabolite, desethylamiodarone. The FWHM lateral resolution measured across an intracellular interface in a high lateral resolution ion images was approximately 550 nm. Overall, this approach provides the basis for studying cellular uptake of pharmaceutical compounds and their metabolites on the single cell level

HLA allele frequencies and susceptibility to COVID-19 in a group of 99 Italian patients

With the aim to individuate alleles that may reflect a higher susceptibility to the disease, in the present study we analyzed the HLA allele frequency distribution in a group of 99 Italian patients affected by a severe or extremely severe form of COVID-19. After the application of Bonferroni's correction for multiple tests, a significant association was found for HLA-DRB1*15:01, -DQB1*06:02 and -B*27:07, after comparing the results to a reference group of 1017 Italian individuals, previously typed in our laboratory. The increased frequencies observed may contribute to identify potential markers of susceptibility to the disease, although controversial results on the role of single HLA alleles in COVID-19 patients have been recently reported

Reduction of T Lymphoma Cells and Immunological Invigoration in a Patient Concurrently Affected by Melanoma and Sezary Syndrome Treated With Nivolumab

Despite the recent availability of several new drugs in hemato-oncology, T-cell lymphomas are still incurable and PD-1 blockade could represent a therapeutic chance for selected patients affected by these malignancies, although further studies are required to understand the biological effects of anti-PD-1 mAbs on neoplastic T-cells and to identify biomarkers for predicting and/or monitoring patients' response to therapy. Sezary Syndrome (SS) represents a rare and aggressive variant of cutaneous T cell lymphoma (CTCL) with a life expectancy of less than 5 years, characterized by the co-presence of neoplastic lymphocytes mainly in the blood, lymph nodes and skin. In this study we analyzed longitudinal blood samples and lesional skin biopsies of a patient concurrently affected by SS and melanoma who underwent 22 nivolumab administrations. In blood, we observed a progressive reduction of SS cell number and a raise in the percentage of normal CD4+ and CD8+ T cells and NK cells over total leukocytes. Eight weeks from the start of nivolumab, these immune cell subsets showed an increase of Ki67 proliferation index that positively correlated with their PD-1 expression. Conversely, SS cells displayed a strong reduction of Ki67 positivity despite their high PD-1 expression. On skin biopsies we observed a marked reduction of SS cells which were no more detectable at the end of therapy. We also found an increase in the percentage of normal CD4+ T cells with a concomitant decrease of that of CD8+ and CD4+ CD8+ T cells, two cell subsets that, however, acquired a cytotoxic phenotype. In summary, our study demonstrated that nivolumab marked reduced SS tumor burden and invigorated immune responses in our patient. Our data also suggest, for the first time, that Ki67 expression in circulating neoplastic and immune cell subsets, as well as an enrichment in T cells with a cytotoxic phenotype in lesional skin could be valuable markers to assess early on treatment SS patients' response to PD-1 blockade, a therapeutic strategy under clinical investigation in CTCL (NCT03385226, NCT04118868)

Investigating the Origin of Seismic Swarms

According to the U.S. Geological Survey’s Earthquake Hazards Program, a seismic swarm is “a localized surge of earth- quakes, with no one shock being conspicuously larger than all other shocks of the swarm. They might occur in a variety of geologic environments and are not known to be indicative of any change in the long- term seismic risk of the region in which they occur” (http://vulcan.wr.usgs.gov/Glossary/ Seismicitydescription_earthquakes.html). The definition reveals how little is actually known about seismic swarms. For example, could certain seismic settings be more prone to swarms? Could a fault zone prone to large energetic earthquakes release part of its stress through seismic swarms? Do swarms keep hazards in balance, or could their onset increase hazards? To gain insight into the nature of seismic swarms in nonvolcanic areas and to better understand their influence on seismic hazards, the Istituto Nazionale di Geofisica e Vulcanologia (INGV) and the German Research Centre for Geoscience (GFZ) began a combined research project within the framework of the Network of European Research Infrastructures for Earthquake Risk Assessment and Mitigation (NERA; see http:// www.nera-eu.org/). The project focused on monitoring swarm activity occurring in the Pollino range in Southern Apennines, Italy.Published361-3721.1. TTC - Monitoraggio sismico del territorio nazionaleN/A or not JCRrestricte