ALBERT

Description: Inhibition of programmed death 1 (PD-1), expressed on activated T cells, can break through immune resistance and elicit durable responses in human melanoma as well as other types of cancers. Canine oral malignant melanoma is one of the most aggressive tumors bearing poor prognosis due to its high metastatic potency. However, there are few effective treatments for the advanced stages of melanoma in veterinary medicine. Only one previous study indicated the potential of the immune checkpoint inhibitor, anti-canine PD-L1 therapeutic antibody in dogs, and no anti-canine PD-1 therapeutic antibodies are currently available. Here, we developed two therapeutic antibodies, rat-dog chimeric and caninized anti-canine PD-1 monoclonal antibodies and evaluated in vitro functionality for these antibodies. Moreover, we conducted a pilot study to determine their safety profiles and clinical efficacy in spontaneously occurring canine cancers. In conclusion, the anti-canine PD-1 monoclonal antibody was relatively safe and effective in dogs with advanced oral malignant melanoma and other cancers. Thus, our study suggests that PD-1 blockade may be an attractive treatment option in canine cancers.

Description: A novel and feasible solution to generate plane spiral orbital angular momentum (PSOAM) vortex beam is proposed in this paper. The general principle of generating PSOAM in circular antenna array (CAA) is deduced, and verified by the simulation of the dipole CAA. Four double-slot Vivaldi antenna elements connect sequentially and are inserted into a CAA, which makes the proposed antenna easily fabricated and fully miniaturized. Both simulated and measured results show that it can generate PSOAM with l = 3 (l is the mode number of vortex wave) at 5 GHz. The vortex phase of l = 3 is observed, the measured peak gain is 5.7 dB. The VSWR remains below 2 from 4 to 6 GHz, which shows the impedance bandwidth of S11 

Description: We study the dynamics of three populations evolving in a two-dimensional discrete grid according to rules of attraction, rejection, or indifference following the framework of the seminal model by Sakoda and we apply it to migration phenomena. An interesting feature of the Sakoda model is the existence of a Potts-like energy which, as a common principle, decreases as time passes by. Here we consider the evolution of two populations until stabilization, then, we perturb this attractor by the inclusion of a third arrival: the immigrants. We show the conditions under which this irruption does not alter significantly the previous attractor (a sociological morphostatic behaviour) or it is dramatically changed (morphogenetic behaviour). We observe empirically that for a morphostatic behaviour the energy decreases while for morphogenesis this energy increases, revealing an escalation of social tension.

Description: Activation of GABAA receptors causes in immature neurons a functionally relevant decrease in the intracellular Cl− concentration ([Cl−]i), a process termed ionic plasticity. Amount and duration of ionic plasticity depends on kinetic properties of [Cl−]i homeostasis. In order to characterize the capacity of Cl− accumulation and to quantify the effect of persistent GABAergic activity on [Cl−]i, we performed gramicidin-perforated patch-clamp recordings from CA3 pyramidal neurons of immature (postnatal day 4–7) rat hippocampal slices. These experiments revealed that inhibition of NKCC1 decreased [Cl−]i toward passive distribution with a time constant of 381 s. In contrast, active Cl− accumulation occurred with a time constant of 155 s, corresponding to a rate of 15.4 µM/s. Inhibition of phasic GABAergic activity had no significant effect on steady state [Cl−]i. Inhibition of tonic GABAergic currents induced a significant [Cl−]i increase by 1.6 mM, while activation of tonic extrasynaptic GABAA receptors with THIP significantly reduced [Cl−]i.. Simulations of neuronal [Cl−]i homeostasis supported the observation, that basal levels of synaptic GABAergic activation do not affect [Cl−]i. In summary, these results indicate that active Cl−-uptake in immature hippocampal neurons is sufficient to maintain stable [Cl−]i at basal levels of phasic and to some extent also to compensate tonic GABAergic activity.

Description: Atmospheric aerosols play an important role in the formation of warm clouds by acting as efficient cloud condensation nuclei (CCN) and their interactions are believed to cool the Earth-Atmosphere system (‘first indirect effect or Twomey effect’) in a highly uncertain manner compared to the other forcing agents. Here we demonstrate using long-term (2003–2016) satellite observations (NASA’s A-train satellite constellations) over the northern Indian Ocean, that enhanced aerosol loading (due to anthropogenic emissions) can reverse the first indirect effect significantly. In contrast to Twomey effect, a statistically significant increase in cloud effective radius (CER, µm) is observed with respect to an increase in aerosol loading for clouds having low liquid water path (LWP 

Description: A nanocomposite material characterized by peroxidase-like properties was developed through the dispersion of platinum nanoparticles (PtNPs) inside a hydrogelic matrix. The integration of the PtNP catalysts within the matrix resulted in their stabilization, preventing aggregation and precipitation in media of environmental interest, characterized by high ionic strength and by the presence of organic solutes. A thorough optimization of the matrix design was aimed at granting optimal diffusion of the reagents, in order to maintain the efficiency of the catalytic action. Such combined features allowed the implementation and prototyping of a colorimetric method for the detection of mercury in environmental water samples. The assay was based on a chromogenic reaction catalyzed by the peroxidase-like activity of PtNPs and its specific inhibition caused by trace amounts of mercury.

Description: Energy band alignment at the heterointerface between CdS and kesterite Cu2ZnSnS4 (CZTS) and its alloys plays a crucial role in determining the efficiency of the solar cells. Whereas Ag alloying of CZTS has been shown to reduce anti-site defects in the bulk and thus rise the efficiency, the electronic properties at the interface with the CdS buffer layer have not been extensively investigated. In this work, we present a detailed study on the band alignment between n-CdS and p-CZTS upon Ag alloying by depth-profiling ultraviolet photoelectron spectroscopy (UPS) and X-ray photoelectron spectroscopy (XPS). Our findings indicate that core-level peaks and the valence band edge of CdS exhibit a significant shift to a lower energy (larger than 0.4 eV) upon the etching of the CdS layer, which can be assigned due to band bending and chemical shift induced by a change in the chemical composition across the interface. Using a simplified model based on charge depletion layer conservation, a significantly larger total charge region depletion width was determined in Ag-alloyed CZTS as compared to its undoped counterpart. Our findings reveal a cliff-like band alignment at both CdS/CZTS and CdS/Ag-CZTS heterointerfaces. However, the conduction-band offset decreases by more than 0.1 eV upon Ag alloying of CZTS. The approach demonstrated here enables nanometer-scale depth profiling of the electronic structure of the p–n junction and can be universally applied to study entirely new platforms of oxide/chalcogenide heterostructures for next-generation optoelectronic devices.

Description: Porous three-dimensional hydrogel scaffolds have an exquisite ability to promote tissue repair. However, because of their high water content and invasive nature during surgical implantation, hydrogels are at an increased risk of bacterial infection. Recently, we have developed elastic biomimetic cryogels, an advanced type of polymeric hydrogel, that are syringe-deliverable through hypodermic needles. These needle-injectable cryogels have unique properties, including large and interconnected pores, mechanical robustness, and shape-memory. Like hydrogels, cryogels are also susceptible to colonization by microbial pathogens. To that end, our minimally invasive cryogels have been engineered to address this challenge. Specifically, we hybridized the cryogels with calcium peroxide microparticles to controllably produce bactericidal hydrogen peroxide. Our novel microcomposite cryogels exhibit antimicrobial properties and inhibit antibiotic-resistant bacteria (MRSA and Pseudomonas aeruginosa), the most common cause of biomaterial implant failure in modern medicine. Moreover, the cryogels showed negligible cytotoxicity toward murine fibroblasts and prevented activation of primary bone marrow-derived dendritic cells ex vivo. Finally, in vivo data suggested tissue integration, biodegradation, and minimal host inflammatory responses when the antimicrobial cryogels, even when purposely contaminated with bacteria, were subcutaneously injected in mice. Collectively, these needle-injectable microcomposite cryogels show great promise for biomedical applications, especially in tissue engineering and regenerative medicine.

Description: Immune cell infiltrates in melanoma have important prognostic value. Gene expression analysis may simultaneously quantify numbers and function of multiple immune cell subtypes in formalin-fixed paraffin-embedded (FFPE) tissues. Prior studies report single gene expression can represent individual immune cell subtypes, but this has not been shown in FFPE melanomas. We hypothesized that gene expression profiling of human melanomas using a new RNA expression technology in FFPE tissue would correlate with the same immune cells identified by immunohistochemistry (IHC). This retrospective study included melanoma specimens analyzed by IHC on tumor tissue microarray (TMA) cores and by gene expression profiling with EdgeSeq Immuno-Oncology Assay using qNPA technology on the corresponding tumors. Standardized gene expression levels were analyzed relative to enumerated cells by IHC using Spearman rank test to calculate r-values. Multivariate analysis was performed by Kruskal–Wallis test. 119 melanoma specimens had both IHC and gene expression information available. There were significant associations between the level of gene expression and its quantified IHC cell marker for CD45+, CD3+, CD8+, CD4+, and CD20+ cells (all p 

Description: The coronavirus SARS-CoV-2 emerging from Wuhan, China has developed into a global epidemic. Here, we combine both human mobility and non-pharmaceutical interventions (social-distancing and suspected-cases isolation) into SEIR transmission model to understand how coronavirus transmits in a global environment. Dynamic trends of region-specific time-variant reproduction number, social-distancing rate, work-resumption rate, and suspected-cases isolation rate have been estimated and plotted for each region by fitting stochastic transmission processes to the real total confirmed cases reported of each region. We find after shutdown in Wuhan, the reproduction number in Wuhan greatly declined from 6·982 (95% CI 2·558–14·668) on January 23rd, 2020 to 1.130 (95% CI 0.289–3.279) on February 7th, 2020, and there was a higher intervention level in terms of social-distancing and suspected-cases isolation in Wuhan than the Chinese average and Western average, for the period from the shutdown in Wuhan to mid-March. Future epidemic trajectories of Western countries up to October 10th, 2020, have been predicted with 95% confidence intervals. Through the scenario simulation, we discover the benefits of earlier international travel ban and rigorous intervention strategies, and the significance of non-pharmaceutical interventions. From a global perspective, it is vital for each country to control the risks of imported cases, and execute rigorous non-pharmaceutical interventions before successful vaccination development.