A web-accessible computer program for calculating electrical potentials and ion activities at cell-membrane surfaces

Increasing evidence indicates that plant responses to ions (uptake/transport, inhibition, and alleviation of inhibition) are dependent upon ion activities at the outer surface of root-cell plasma membranes (PMs) rather than activities in the bulk-phase rooting medium

Understanding resistance vs. susceptibility in visceral leishmaniasis using mouse models of Leishmania infantum Infection

Every year, up to 90,000 new cases of Visceral Leishmaniasis and 30,000 resultant deaths are estimated to occur worldwide. Such numbers give relevance to the continuous study of this complex form of the disease: a zoonosis and an anthroponosis; two known etiological agents (Leishmania infantum and L. donovani, respectively); with an estimated average ratio of 1 symptomatic per 10 asymptomatic individuals; and sometimes associated with atypical clinical presentations. This complexity, which results from a long co-evolutionary process involving vector-host, host-pathogen, and pathogen-vector interactions, is still not completely understood. The determinants of visceralization are not fully defined and the dichotomy resistance vs. susceptibility remains unsolved, translating into obstacles that delay the progress of global disease control. Inbred mouse models, with different susceptibility patterns to Leishmania infection, have been very useful in exploring this dichotomy. BALB/c and C57BL/6 mice were described as susceptible strains to L. donovani visceral infection, while SV/129 was considered resistant. Here, we used these three mouse models, but in the context of L. infantum infection, the other Leishmania species that cause visceral disease in humans, and dynamically compared their local and systemic infection-induced immune responses in order to establish a parallel and to ultimately better understand susceptibility vs. resistance in visceral leishmaniasis. Overall, our results suggest that C57BL/6 mice develop an intermediate "infection-phenotype" in comparison to BALB/c and SV/129 mouse strains, considering both the splenic parasite burden and the determined target organs weights. However, the immune mechanisms associated with the control of infection seem to be different in each mouse strain. We observed that both BALB/c and SV/129, but not C57BL/6 mice, show an infection-induced increase of splenic T follicular helper cells. On the other hand, differences detected in terms of CD21 expression by B cells early after infection, together with the quantified anti-Leishmania specific antibodies, suggest that SV/129 are faster than BALB/c and C57BL/6 mice in the assembly of an efficient B-cell response. Additionally, we observed an infection-induced increase in polyfunctional CD4+ T cells in the resistant SV/129 model, opposing an infection-induced increase in CD4+IL-10+ cells in susceptible BALB/c mice. Our data aligns with the observations reported for L. donovani infection and suggest that not only a single mechanism, but an interaction of several could be necessary for the control of this parasitic disease.The research leading to these results has received funding from the project NORTE-01-0145-FEDER-000012, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). PC was supported by Foundation for Science and Technology (FCT), Portugal, through the individual grant SFRH/BD/121252/2016

Implementation of a Toffoli Gate with Superconducting Circuits

The quantum Toffoli gate allows universal reversible classical computation. It is also an important primitive in many quantum circuits and quantum error correction schemes. Here we demonstrate the realization of a Toffoli gate with three superconducting transmon qubits coupled to a microwave resonator. By exploiting the third energy level of the transmon qubit, the number of elementary gates needed for the implementation of the Toffoli gate, as well as the total gate time can be reduced significantly in comparison to theoretical proposals using two-level systems only. We characterize the performance of the gate by full process tomography and Monte Carlo process certification. The gate fidelity is found to be $68.5\pm0.5$%.Comment: 4 pages, 5figure

Inhibition of CXCR2 Plays a Pivotal Role in Re-Sensitizing Ovarian Cancer to Cisplatin Treatment

cDNA microarray data conducted by our group revealed overexpression of CXCL2 and CXCL8 in ovarian cancer (OC) microenvironment. Herein, we have proven that the chemokine receptor, CXCR2, is a pivotal molecule in re-sensitizing OC to cisplatin, and its inhibition decreases cell proliferation, viability, tumor size in cisplatinresistant cells, as well as reversed the overexpression of mesenchymal epithelium transition markers. Altogether, our study indicates a central effect of CXCR2 in preventing tumor progression, due to acquisition of cisplatin chemoresistant phenotype by tumor cells, and patients’ high lethality rate. We found that the overexpression of CXCR2 by OC cells is persistent and anomalously confined to the cellular nuclei, thus pointing to an urge in developing highly lipophilic molecules that promptly permeate cells, bind to and inhibit nuclear CXCR2 to fight OC, instead of relying on the high-cost genetic engineered cells.acknowledge financial support from CAPES, FAPES and CNPq, as well as the Biotechnology Program/ RENORBIO from the Federal University of Espirito Santo, Espirito Santo, Brazil; Institute of Pathology and Molecular Immunology (IPATIMUP) and the Institute of Innovation and Health Research (I3s), Porto, Portugal

A new interpretation of total column BrO during Arctic spring

Emission of bromine from sea-salt aerosol, frost flowers, ice leads, and snow results in the nearly complete removal of surface ozone during Arctic spring. Regions of enhanced total column BrO observed by satellites have traditionally been associated with these emissions. However, airborne measurements of BrO and O3 within the convective boundary layer (CBL) during the ARCTAS and ARCPAC field campaigns at times bear little relation to enhanced column BrO. We show that the locations of numerous satellite BrO "hotspots" during Arctic spring are consistent with observations of total column ozone and tropopause height, suggesting a stratospheric origin to these regions of elevated BrO. Tropospheric enhancements of BrO large enough to affect the column abundance are also observed, with important contributions originating from above the CBL. Closure of the budget for total column BrO, albeit with significant uncertainty, is achieved by summing observed tropospheric partial columns with calculated stratospheric partial columns provided that natural, short-lived biogenic bromocarbons supply between 5 and 10 ppt of bromine to the Arctic lowermost stratosphere. Proper understanding of bromine and its effects on atmospheric composition requires accurate treatment of geographic variations in column BrO originating from both the stratosphere and troposphere. Copyright 2010 by the American Geophysical Union

Voxel-wise comparisons of cellular microstructure and diffusion-MRI in mouse hippocampus using 3D Bridging of Optically-clear histology with Neuroimaging Data (3D-BOND)

A key challenge in medical imaging is determining a precise correspondence between image properties and tissue microstructure. This comparison is hindered by disparate scales and resolutions between medical imaging and histology. We present a new technique, 3D Bridging of Optically-clear histology with Neuroimaging Data (3D-BOND), for registering medical images with 3D histology to overcome these limitations. Ex vivo 120 × 120 × 200 μm resolution diffusion-MRI (dMRI) data was acquired at 7 T from adult C57Bl/6 mouse hippocampus. Tissue was then optically cleared using CLARITY and stained with cellular markers and confocal microscopy used to produce high-resolution images of the 3D-tissue microstructure. For each sample, a dense array of hippocampal landmarks was used to drive registration between upsampled dMRI data and the corresponding confocal images. The cell population in each MRI voxel was determined within hippocampal subregions and compared to MRI-derived metrics. 3D-BOND provided robust voxel-wise, cellular correlates of dMRI data. CA1 pyramidal and dentate gyrus granular layers had significantly different mean diffusivity (p > 0.001), which was related to microstructural features. Overall, mean and radial diffusivity correlated with cell and axon density and fractional anisotropy with astrocyte density, while apparent fibre density correlated negatively with axon density. Astrocytes, axons and blood vessels correlated to tensor orientation

Therapeutic Application of an Ag-Nanoparticle-PNIPAAm-Modified Eggshell Membrane Construct for Dermal Regeneration and Reconstruction

Current therapeutic treatments for the repair and/or replacement of damaged skin following disease or traumatic injury is severely limited. The chicken eggshell membrane (ESM) is a unique material: its innate physical and mechanical characteristics offer optimal barrier properties and, as a naturally derived extract, it demonstrates inherent biocompatibility/biodegradability. To further enhance its therapeutic and clinical potential, the ESM can be modified with the thermo-responsive polymer, poly(N-isopropylacrylAmide) (PNIPAAm) as well as the incorporation of (drug-loaded) silver nanoparticles (AgNP); essentially, by a simple change in temperature, the release and delivery of the NP can be targeted and controlled. In this study, ESM samples were isolated using a decellularization protocol, and the physical and mechanical characteristics were profiled using SEM, FT-IR, DSC and DMA. PNIPAAm was successfully grafted to the ESM via amidation reactions and confirmed using FT-IR, which demonstrated the distinctive peaks associated with Amide A (3275 cm−1), Amide B (2970 cm−1), Amide I (1630 cm−1), Amide II (1535 cm−1), CH2, CH3 groups, and Amide III (1250 cm−1) peaks. Confirmation of the incorporation of AgNP onto the stratified membrane was confirmed visually with SEM, qualitatively using FT-IR and also via changes in absorbance at 380 nm using UV-Vis spectrophotometry during a controlled release study for 72 h. The biocompatibility and cytotoxicity of the novel constructs were assessed using human dermal fibroblast (HDFa) and mouse dermal fibroblast (L929) cells and standard cell culture assays. Metabolic activity assessment (i.e., MTS assay), LDH-release profiles and Live/Dead staining demonstrated good attachment and spreading to the samples, and high cell viability following 3 days of culture. Interestingly, longer-term viability (>5 days), the ESM-PNIPAAm and ESM-PNIPAAm (AgNP) samples showed a greater and sustained cell viability profile. In summary, the modified and enhanced ESM constructs were successfully prepared and characterized in terms of their physical and mechanical profiles. AgNP were successfully loaded into the construct and demonstrated a desirable release profile dependent on temperature modulation. Fibroblasts cultured on the extracted ESM samples and ESM-PNIPAAm demonstrated high biocompatibility in terms of high cell attachment, spreading, viability and proliferation rates. As such, this work summarizes the development of an enhanced ESM-based construct which may be exploited as a clinical/therapeutic wound dressing as well as a possible application as a novel biomaterial scaffold for drug development

Integrable Models of Internal Gravity Water Waves Beneath a Flat Surface

A two-layer fluid system separated by a pycnocline in the form of an internal wave is considered. The lower layer is bounded below by a flat bottom and the upper layer is bounded above by a flat surface. The fluids are incompressible and inviscid and Coriolis forces as well as currents are taken into consideration. A Hamiltonian formulation is presented and appropriate scaling leads to a KdV approximation. Additionally, considering the lower layer to be infinitely deep leads to a Benjamin-Ono approximation

Improving ductal carcinoma in situ classification by convolutional neural network with exponential linear unit and rank-based weighted pooling

Ductal carcinoma in situ (DCIS) is a pre-cancerous lesion in the ducts of the breast, and early diagnosis is crucial for optimal therapeutic intervention. Thermography imaging is a non-invasive imaging tool that can be utilized for detection of DCIS and although it has high accuracy (~88%), it is sensitivity can still be improved. Hence, we aimed to develop an automated artificial intelligence-based system for improved detection of DCIS in thermographs. This study proposed a novel artificial intelligence based system based on convolutional neural network (CNN) termed CNN-BDER on a multisource dataset containing 240 DCIS images and 240 healthy breast images. Based on CNN, batch normalization, dropout, exponential linear unit and rank-based weighted pooling were integrated, along with L-way data augmentation. Ten runs of tenfold cross validation were chosen to report the unbiased performances. Our proposed method achieved a sensitivity of 94.08±1.22%, a specificity of 93.58±1.49 and an accuracy of 93.83±0.96. The proposed method gives superior performance than eight state-of-theart approaches and manual diagnosis. The trained model could serve as a visual question answering system and improve diagnostic accuracy.British Heart Foundation Accelerator Award, UKRoyal Society International Exchanges Cost Share Award, UK RP202G0230Hope Foundation for Cancer Research, UK RM60G0680Medical Research Council Confidence in Concept Award, UK MC_PC_17171MINECO/FEDER, Spain/Europe RTI2018-098913-B100 A-TIC-080-UGR1