Waughsvendsen9247

Neoadjuvant immune checkpoint blockade has shown promising clinical activity. Here, we characterized early kinetics in tumor-infiltrating and circulating immune cells in oral cancer patients treated with neoadjuvant anti-PD-1 or anti-PD-1/CTLA-4 in a clinical trial (NCT02919683). Tumor-infiltrating CD8 T cells that clonally expanded during immunotherapy expressed elevated tissue-resident memory and cytotoxicity programs, which were already active prior to therapy, supporting the capacity for rapid response. Systematic target discovery revealed that treatment-expanded tumor T cell clones in responding patients recognized several self-antigens, including the cancer-specific antigen MAGEA1. Treatment also induced a systemic immune response characterized by expansion of activated T cells enriched for tumor-infiltrating T cell clonotypes, including both pre-existing and emergent clonotypes undetectable prior to therapy. The frequency of activated blood CD8 T cells, notably pre-treatment PD-1-positive KLRG1-negative T cells, was strongly associated with intra-tumoral pathological response. These results demonstrate how neoadjuvant checkpoint blockade induces local and systemic tumor immunity.Leishmaniasis is a major tropical disease with increasing global incidence. Due to limited therapeutic options with severe drawbacks, the discovery of alternative treatments based on natural bioactive compounds is important. In our previous studies we have pointed out the antileishmanial activities of olive tree-derived molecules. In this study, we aimed to investigate the in vitro and in vivo antileishmanial as well as the in vivo immunomodulatory effects of oleocanthal, a molecule that has recently gained increasing scientific attention. Pure oleocanthal was isolated from extra virgin olive oil through extraction and chromatography techniques. The in vitro antileishmanial effects of oleocanthal were examined with a resazurin-based assay, while its in vivo efficacy was evaluated in Leishmania major-infected BALB/c mice by determining footpad induration, parasite load in popliteal lymph nodes, histopathological outcome, antibody production, cytokine profile of stimulated splenocytes and immune gene expression, at three weeks after the termination of treatment. Oleocanthal demonstrated in vitro antileishmanial effect against both L. major promastigotes and intracellular amastigotes. This effect was further documented in vivo as demonstrated by the suppressed footpad thickness, the decreased parasite load and the inflammatory cell influx at the infection site. Oleocanthal treatment led to the dominance of a Th1-type immunity linked with resistance against the disease. This study establishes strong scientific evidence for olive tree-derived natural products as possible antileishmanial agents and provides an adding value to the scientific research of oleocanthal.Simple, low-cost, and high-performance atmospheric water harvesting (AWH) still remains challenging in the context of global water shortage. Here, we present a simple and low-cost macroporous hydrogel for high-performance AWH to address this challenge. We employed an innovative strategy of pore foaming and vacuum drying to rationally fabricate a macroporous hydrogel. The hydrogel is endowed with a macroporous structure and a high specific surface area, enabling sufficient contact of the inner sorbent with outside air and high-performance AWH. The experiments demonstrate that macroporous hydrogels can achieve high-performance AWH with a broad range of sorption humidity [relative humidity (RH) from 100% to even lower than 20%], high water sorption capacity (highest 433.72% of hydrogel's own weight at ∼98% RH, 25 °C within 60 h), rapid vapor capturing (the sorption efficiency is as high as 0.32 g g-1 h-1 in the first 3 h at 90% RH, 25 °C), unique durability, low desorption temperature (∼50 °C, lowest), and high water-releasing rate (release 99.38% of the sorbed water under 500 W m-2 light for 6 h). The results show that this macroporous hydrogel can sorb water more than 193.46% of its own weight overnight (13 h) at a RH of ∼90%, 25 °C and release as high as 99.38% of the sorbed water via the photothermal effect. VE821 It is estimated that the daily water yield can reach up to approximately 2.56 kg kg-1 day-1 in real outdoor conditions, enabling daily minimum water consumption of an adult. Our simple, affordable, and easy-to-scale-up macroporous hydrogel can not only unleash the unlimited possibilities for large-scale and high-performance AWH but also offer promising opportunities for functional materials, soft matter, flexible electronics, tissue engineering, and biomedical applications.Small field dosimetry is significantly different from the dosimetry of broad beams due to loss of electron side scatter equilibrium, source occlusion, and effects related to the choice of detector. However, use of small fields is increasing with the increase in indications for intensity-modulated radiation therapy and stereotactic body radiation therapy, and thus the need for accurate dosimetry is ever more important. Here we propose to leverage machine learning (ML) strategies to reduce the uncertainties and increase the accuracy in determining small field output factors (OFs). Linac OFs from a Varian TrueBeam STx were calculated either by the treatment planning system (TPS) or measured with a W1 scintillator detector at various multi-leaf collimator (MLC) positions, jaw positions, and with and without contribution from leaf-end transmission. The fields were defined by the MLCs with the jaws at various positions. Field sizes between 5 and 100 mm were evaluated. Separate ML regression models were generated based on the TPS calculated or the measured datasets. Accurate predictions of small field OFs at different field sizes (FSs) were achieved independent of jaw and MLC position. A mean and maximum % relative error of 0.38 ± 0.39% and 3.62%, respectively, for the best-performing models based on the measured datasets were found. The prediction accuracy was independent of contribution from leaf-end transmission. Several ML models for predicting small field OFs were generated, validated, and tested. Incorporating these models into the dose calculation workflow could greatly increase the accuracy and robustness of dose calculations for any radiotherapy delivery technique that relies heavily on small fields.Animal societies exhibit complex dynamics that require multi-level descriptions. They are difficult to model, as they encompass information at different levels of description, such as individual physiology, individual behaviour, group behaviour and features of the environment. The collective behaviour of a group of animals can be modelled as a dynamical system. Typically, models of behaviour are either macroscopic (differential equations of population dynamics) or microscopic (such as Markov chains, explicitly specifying the spatio-temporal state of each individual). These two kind of models offer distinct and complementary descriptions of the observed behaviour. Macroscopic models offer mean field description of the collective dynamics, where collective choices are considered as the stable steady states of a nonlinear system governed by control parameters leading to bifurcation diagrams. Microscopic models can be used to perform computer simulations or as building blocks for robot controllers, at the individual level, of the observed spatial behaviour of animals. Here, we present a methodology to translate a macroscopic model into different microscopic models. We automatically calibrate the microscopic models so that the resulting simulated collective dynamics fit the solutions of the reference macroscopic model for a set of parameter values corresponding to a bifurcation diagram leading to multiple steady states. We apply evolutionary algorithms to simultaneously optimize the parameters of the models at different levels of description. This methodology is applied, in simulation, to an experimentally validated shelter-selection problem solved by gregarious insects and robots. Our framework can be used for multi-level modelling of collective behaviour in animals and robots.Radiomics features extracted from medical images have been widely reported to be useful in the patient specific outcome modeling for variety of assessment and prediction purposes. Successful application of radiomics features as imaging biomarkers, however, is dependent on the robustness of the approach to the variation in each step of the modeling workflow. Variation in the input image quality is one of the main sources that impacts the reproducibility of radiomics analysis when a model is applied to broader range of medical imaging data. The quality of medical image is generally affected by both the scanner related factors such as image acquisition/reconstruction settings and the patient related factors such as patient motion. This article aimed to review the published literatures in this field that reported the impact of various imaging factors on the radiomics features through the change in image quality. The literatures were categorized by different imaging modalities and also tabulated based on the imaging parameters and the class of radiomics features included in the study. Strategies for image quality standardization were discussed based on the relevant literatures and recommendations for reducing the impact of image quality variation on the radiomics in multi-institutional clinical trial were summarized at the end of this article.Deployable membranes are being increasingly applied in numerous space projects owing to their light weight, small stowage volume and capacity for use at large scales. The geometric design of biomimetic folding is studied to design crease patterns for triangular deployable membranes applied in space. Various crease designs for triangular membranes based on leaf-in, leaf-out and orthogonal patterns are put forward, especially patterns composed of triangular and hexagonal units. In order to analyse the membrane folding method based on biomimetic folding, a set of evaluation indices, including linear dimension ratio, deployment ratio, crease length and junction number, are established. The indices for various membrane folding patterns are calculated according to the crease distributions and geometric relations. Furthermore, a parametric study of crease parameters is performed to determine how the parameters affect folding behaviour and deployment efficiency. These indices can provide an indication to help with the selection of crease patterns and folding parameters for triangular deployable membranes according to the required performance and space mission requirements.Fish scale inspired materials and structures can provide advanced mechanical properties and functionalities. These materials, inspired by fish scales, take the form of either composite materials or multi-material discrete exoskeleton type structures. Over the last decade they have been under intense scrutiny for generating tailorable and tunable stiffness, penetration and fracture resistance, buckling prevention, nonlinear damping, hydrodynamic and camouflaging functions. Such programmable behavior emerges from leveraging their unique morphology and structure-property relationships. Several advanced tools for characterization, manufacturing, modeling and computation have been employed to understand and discover their behavior. With the rapid proliferation of additive manufacturing techniques and advances in modeling and computational methods, this field is seeing renewed efforts to realize even more ambitious designs. In this paper we present a review and recapitulation of the state-of-the art of fish scale inspired materials.