•Novel machine learning algorithm based on physics informed neural networks (PINNs) for approximating solutions of forward and inverse problems for radiative transfer.•Fast, robust and accurate ...approach, independent of the equation dimensionality.•Estimates on the generalization error of PINNs for the unsteady and steady forward problem.•Extensive numerical experiments demonstrating the accuracy and efficiency of the proposed algorithm.
We propose a novel machine learning algorithm for simulating radiative transfer. Our algorithm is based on physics informed neural networks (PINNs), which are trained by minimizing the residual of the underlying radiative transfer equations. We present extensive experiments and theoretical error estimates to demonstrate that PINNs provide a very easy to implement, fast, robust and accurate method for simulating radiative transfer. We also present a PINN based algorithm for simulating inverse problems for radiative transfer efficiently.
The engineering of future generations of nanodelivery systems aims at the creation of multifunctional vectors endowed with improved circulation, enhanced targeting and responsiveness to the ...biological environment. Moving past purely bio-inert systems, researchers have begun to create nanoparticles capable of proactively interacting with the biology of the body. Nature offers a wide-range of sources of inspiration for the synthesis of more effective drug delivery platforms. Because the nano-bio-interface is the key driver of nanoparticle behavior and function, the modification of nanoparticles’ surfaces allows the transfer of biological properties to synthetic carriers by imparting them with a biological identity. Modulation of these surface characteristics governs nanoparticle interactions with the biological barriers they encounter. Building off these observations, we provide here an overview of virus- and cell-derived biomimetic delivery systems that combine the intrinsic hallmarks of biological membranes with the delivery capabilities of synthetic carriers. We describe the features and properties of biomimetic delivery systems, recapitulating the distinctive traits and functions of viruses, exosomes, platelets, red and white blood cells. By mimicking these biological entities, we will learn how to more efficiently interact with the human body and refine our ability to negotiate with the biological barriers that impair the therapeutic efficacy of nanoparticles.
In a perfect sequence of events, nanoparticles (NPs) are injected into the bloodstream where they circulate until they reach the target tissue. The ligand on the NP surface recognizes its specific ...receptor expressed on the target tissue and the drug is released in a controlled manner. However, once injected in a physiological environment, NPs interact with biological components and are surrounded by a protein corona (PC). This can trigger an immune response and affect NP toxicity and targeting capabilities. In this review, we provide a survey of recent findings on the NP-PC interactions and discuss how the PC can be used to modulate both cytotoxicity and the immune response as well as to improve the efficacy of targeted delivery of nanocarriers.
Abstract
Physics-informed neural networks (PINNs) have recently been very successfully applied for efficiently approximating inverse problems for partial differential equations (PDEs). We focus on a ...particular class of inverse problems, the so-called data assimilation or unique continuation problems, and prove rigorous estimates on the generalization error of PINNs approximating them. An abstract framework is presented and conditional stability estimates for the underlying inverse problem are employed to derive the estimate on the PINN generalization error, providing rigorous justification for the use of PINNs in this context. The abstract framework is illustrated with examples of four prototypical linear PDEs. Numerical experiments, validating the proposed theory, are also presented.
Bone defects pose a heavy burden on patients, orthopedic surgeons, and public health resources. Various pathological conditions cause bone defects including trauma, tumors, inflammation, ...osteoporosis, and so forth. Auto‐ and allograft transplantation have been developed as the most commonly used clinic treatment methods, among which autologous bone grafts are the golden standard. Yet the repair of bone defects, especially large‐volume defects in the geriatric population or those complicated with systemic disease, is still a challenge for regenerative medicine from the clinical perspective. The fast development of biomaterials and nanomedicine favors the emergence and promotion of efficient bone regeneration therapies. In this review, we briefly summarize the progress of novel biomaterial and nanomedical approaches to bone regeneration and then discuss the current challenges that still hinder their clinical applications in treating bone defects.
We present an overview of common causes of bone defects, the unmet clinical needs, and the utility of biomaterials and nanotechnology to facilitate bone regeneration. Besides, we propose several key approaches to improve bone repair strategies. This perspective provides a guidance for future research direction of bone repair to improve treatment efficiency in both clinical and research perspectives.
In the field of oncology research, a deeper understanding of tumor biology has shed light on the role of environmental conditions surrounding cancer cells. In this regard, targeting the tumor ...microenvironment has recently emerged as a new way to access this disease. In this work, a novel extracellular matrix (ECM)-targeting nanotherapeutic was engineered using a lipid-based nanoparticle chemically linked to an inhibitor of the ECM-related enzyme, lysyl oxidase 1 (LOX), that inhibits the crosslinking of elastin and collagen fibers. We demonstrated that, when the conjugated vesicles were loaded with the chemotherapeutic epirubicin, superior inhibition of triple negative breast cancer (TNBC) cell growth was observed both in vitro and in vivo. Moreover, in vivo results displayed prolonged survival, minimal cytotoxicity, and enhanced biocompatibility compared to free epirubicin and epirubicin-loaded nanoparticles. This all-in-one nano-based ECM-targeting chemotherapeutic may provide a key-enabling technology for the treatment of TNBC.
Inflammation and Cancer: In Medio Stat Nano Molinaro, Roberto; Corbo, Claudia; Livingston, Megan ...
Current medicinal chemistry,
01/2018, Letnik:
25, Številka:
34
Journal Article
Recenzirano
Odprti dostop
Cancer treatment still remains a challenge due to the several limitations of currently used chemotherapeutics, such as their poor pharmacokinetics, unfavorable chemical properties, as well as ...inability to discriminate between healthy and diseased tissue. Nanotechnology offered potent tools to overcome these limitations. Drug encapsulation within a delivery system permitted i) to protect the payload from enzymatic degradation/ inactivation in the blood stream, ii) to improve the physicochemical properties of poorly water-soluble drugs, like paclitaxel, and iii) to selectively deliver chemotherapeutics to the cancer lesions, thus reducing the off-target toxicity, and promoting the intracellular internalization. To accomplish this purpose, several strategies have been developed, based on biological and physical changes happening locally and systemically as a consequence of tumorigenesis. Here, we will discuss the role of inflammation in the different steps of tumor development and the strategies based on the use of nanoparticles that exploit the inflammatory pathways in order to selectively target the tumor-associated microenvironment for therapeutic and diagnostic purposes.
The discovery of paclitaxel (PTX) has been a milestone in anti-cancer therapy and has promoted the development and marketing of various formulations that have revolutionized the therapeutic approach ...towards several malignancies. Despite its peculiar anti-cancer activity, the physico-chemical properties of PTX compromise the administration of the compound in polar media. Because of this, since the development of the first Food and Drug Administration (FDA)-approved formulation (Taxol
), consistent efforts have been made to obtain suitable delivery systems able to preserve/increase PTX efficacy and to overcome the side effects correlated to the presence of some excipients. The exploitation of natural polymers as potential materials for drug delivery purposes has favored the modulation of the bioavailability and the pharmacokinetic profiles of the drug, and in this regard, several formulations have been developed that allow the controlled release of the active compound. In this mini-review, the recent advances concerning the design and applications of natural polymer-based hydrogels containing PTX-loaded biocompatible nanocarriers are discussed. The technological features of these formulations as well as the therapeutic outcome achieved following their administration will be described, demonstrating their potential role as innovative systems to be used in anti-tumor therapy.
Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, is a chronic inflammatory condition of the gastrointestinal (GI) tract. Currently, it is treated with ...immunosuppressant or biologics that often induce severe adverse effects. Thus, there is an urgent clinical need for more specific treatments. To provide a valid therapeutic tool for IBD therapy, in this work we developed biomimetic nanovesicles by manipulating leukocyte membranes to exploit mechanisms of T-cell recruitment during inflammation. A subset of T-lymphocytes participates in homing to inflamed tissue in the gastrointestinal tract by overexpressing the α4β7 integrin, which is responsible for binding to its receptor on the endothelial membrane, the mucosal addressin cell adhesion molecule 1. Based on this principle, we engineered biomimetic vesicles, referred to as specialized leukosomes (SLKs), which are leukocyte-like carriers 'doped' with the α4β7 integrin over-induced in purified immune cells. We tested SLKs in an in vivo murine model of IBD induced by treatment with dextran sulfate sodium. Notably, treatment of IBD mice with SLKs allowed us to observe a reduction of inflammation (favorable modulation of both pro- and anti-inflammatory genes, as well as reduction of immune cells infiltration into the colon tissue), and a consequent enhanced intestinal repair (low epithelial damage). In this study, we demonstrate that biological-derived nanoparticles can be used not only as naturally targeted drug delivery systems, but also as nano-therapeutics endowed with intrinsic anti-inflammatory properties.
Abstract
Milky Way Cepheid variables with accurate Hubble Space Telescope photometry have been established as standards for primary calibration of the cosmic distance ladder to achieve a ...percent-level determination of the Hubble constant (
H
0
). These 75 Cepheid standards are the fundamental sample for investigation of possible residual systematics in the local
H
0
determination due to metallicity effects on their period–luminosity relations. We obtained new high-resolution (
R
∼ 81,000), high-signal-to-noise (S/N ∼ 50–150) multiepoch spectra of 42 out of 75 Cepheid standards using the ESPaDOnS instrument at the 3.6 m Canada–France–Hawaii Telescope. Our spectroscopic metallicity measurements are in good agreement with the literature values with systematic differences up to 0.1 dex due to different metallicity scales. We homogenized and updated the spectroscopic metallicities of all 75 Milky Way Cepheid standards and derived their multiwavelength (
GVIJHK
s
) period–luminosity–metallicity and period–Wesenheit–metallicity relations using the latest Gaia parallaxes. The metallicity coefficients of these empirically calibrated relations exhibit large uncertainties due to low statistics and a narrow metallicity range (ΔFe/H = 0.6 dex). These metallicity coefficients are up to 3 times better constrained if we include Cepheids in the Large Magellanic Cloud and range between −0.21 ± 0.07 and −0.43 ± 0.06 mag dex
−1
. The updated spectroscopic metallicities of these Milky Way Cepheid standards were used in the Cepheid–supernovae distance ladder formalism to determine
H
0
= 72.9 ± 1.0 km s
−1
Mpc
−1
, suggesting little variation (∼0.1 km s
−1
Mpc
−1
) in the local
H
0
measurements due to different Cepheid metallicity scales.
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