Modelling neuromuscular blockade: a stochastic approach based on clinical data

During surgical interventions, a muscle relaxant drug is frequently administered with the objective of inducing muscle paralysis. Clinical environment and patient safety issues lead to a huge variety of situations that must be taken into account requiring intensive simulation studies. Hence, population models are crucial for research and development in this field.

This work develops a stochastic population model for the neuromuscular blockade (NMB) (muscle paralysis) level induced by atracurium based on a deterministic individual model already proposed in the literature. To achieve this goal, a joint Lognormal distribution is considered for the patient-dependent parameters. This study is based on clinical data collected during general anaesthesia. The procedure developed enables to construct a reliable reference bank of parametrized models that not only reproduces the overall features of the NMB, but also the inter-individual variability characteristic of physiological signals. It turns out that this bank constitutes a fundamental tool to support research on identification and control algorithms and is suitable to be integrated in clinical decision support systems.     

A mean field approach to Coulomb blockade for a disordered assembly of quantum dots

The Coulomb blockade (CB) in quantum dots (QDs) is by now well documented. It has been used to guide the fabrication of single electron transistors. Even the most sophisticated techniques for synthesizing QDs (e.g. MOCVD/MBE) result in an assembly in which a certain amount of disorder is inevitable. On the other hand, theoretical approaches to CB limit themselves to an analysis of a single QD. In the present work we consider two types of disorders: (i) size disorder; e.g. QDs have a distribution of sizes which could be unimodal or bimodal in nature. (ii) Potential disorder with the confining potential assuming a variety of shapes depending on growth condition and external fields. We assume a Gaussian distribution in disorder in both size and potential and employ a simplified mean field theory. To do this we rely on the scaling laws for the CB (also termed as Hubbard U) obtained for an isolated QD [1]. We analyze the distribution in the Hubbard U as a consequence of disorder and observe that Coulomb blockade is partially suppressed by the disorder. Further, the distribution in U is a skewed Gaussian with enhanced broadening.      

Coulomb blockade sensors based on nanostructured mesoporous silicon

Mesoporous silicon (mesoPS) is a nanosponge where Si nanocrystals are interconnected forming a disordered 3D array. The electronic characteristics of this material are particularly interesting, due to some intriguing effects, such as a huge increase of conductivity, reversible insulator-to-metal transition and n- or p-type doping of the nanocrystals, exhibited in presence of donor or acceptor molecules like NH₃ and NO₂. Here we report on the observation of a sharp conductance gap, which can be ascribed to Coulomb blockade phenomena. Moreover, we show that the width of the gap can be tuned by NO₂ molecules, so that the fabrication of highly sensitive threshold sensors is possible. Our results suggest that electrochemical etching of heavily doped Si can be used as a simple self-assembly technique for the production of Si nanocrystal arrays and for the fabrication of sensitive nanosensors.     

Size-dependent single electron tunneling effect in Au nanoparticles

We investigated single electron tunneling (SET) behavior of dodecanethiol-coated Au nanoparticles of two different sizes (average sizes are 5 nm and 2 nm) using nanogap electrodes, which have a well-defined gap size, at various temperatures. The Coulomb staircases and the Coulomb gap near-zero bias voltage caused by the suppression of the tunneling electrons due to the Coulomb blockade effect were observed in the current-voltage (I-V) curves of both sizes of nanoparticles at a low temperature (10 K). At room temperature, the Coulomb gap was observed only in the I-V curve of the smaller nanoparticles. This result indicates that the charging energy of the smaller nanoparticles is enough to overcome the thermal energy at room temperature. This suggests that it is possible to operate the SET devices at room temperature using the smaller nanoparticles as a Coulomb island.     

Coulomb Blockade of a Mesoscopic RLC Circuit

The quantum theory of the mesoscopic RLC circuit and the condition for Coulomb blockade are given by using canonical quantization and a unitary transformation from the classical equation of motion. Our results show that there is a threshold voltage _T in the circuit. The threshold voltage is related not only to the junction capacitance and inductance, but also to the resistance of the circuit. Generally speaking, the larger the resistance, the larger the threshold voltage. This clarifies the phenomenon of the Coulomb blockade of the dissipative mesoscopic circuit.     

Analytical result of the effect of spin scattering and impurity-assistance on magnetoresistance in doped magnetic tunneling junctions

An extended tunneling Hamiltonian method is proposed to study the temperature-dependent tunneling magnetoresistance (TMR) in doped magnetic tunnel junctions. It is found that for nonmagnetic dopants (Si), impurity-assisted tunneling is mainly elastic, giving rise to a weak spin polarization, thereby reduces the overall TMR, while for magnetic ions (Ni), the collective excitation of local spins in δ-doped magnetic layer contributes to the severe drop of TMR and the behavior of the variation of TMR with temperature different from that for Si-doping. The theoretical results can reproduce the main characteristic features of experiments. Received 13 January 2002 / Received in final form 30 November 2002 Published online 6 March 2003 RID="a" ID="a"e-mail: yctao12@163.com     

玻璃中的半导体量子点

介绍了玻璃中的半导体量子点。对玻璃中半导体量子点的生长过程、量子的电子态，量子尺寸效应、库仑阻塞效应及介电效应，做了比较全面的介绍。讨论了量子点的应用及发展前景。     

Enhancing Triple Negative Breast Cancer Immunotherapy by ICG‐Templated Self‐Assembly of Paclitaxel Nanoparticles

Combination cancer immunotherapy has shown promising potential for simultaneously eliciting antitumor immunity and modulating the immunosuppressive tumor microenvironment (ITM). However, combination immunotherapy with multiple regimens suffers from the varied chemo‐physical properties and inconsistent pharmacokinetic profiles of the different therapeutics. To achieve tumor‐specific codelivery of the immune modulators, an indocyanine green (ICG)‐templated self‐assembly strategy for preparing dual drug‐loaded two‐in‐one nanomedicine is reported. ICG‐templated self‐assembly of paclitaxel (PTX) nanoparticles (ISPN), and the application of ISPN for combination immunotherapy of the triple negative breast cancer (TNBC) are demonstrated. The ISPN show satisfied colloidal stability and high efficacy for tumor‐specific codelivery of ICG and PTX through the enhanced tumor permeability and retention effect. Upon laser irradiation, the ICG component of ISPN highly efficiently induces immunogenic cell death of the tumor cells via activating antitumor immune response through photodynamic therapy. Meanwhile, PTX delivered by ISPN suppresses the regulatory T lymphocytes (T_regs) to combat ITM. The combination treatment of TNBC with ISPN and αPD‐L1‐medaited immune checkpoint blockade therapy displays a synergistic effect on tumor regression, metastasis inhibition, and recurrence prevention. Overall, the ICG‐templated nanomedicine may represent a robust nanoplatform for combination immunotherapy.     

Inhibition of Immunosuppressive Tumors by Polymer‐Assisted Inductions of Immunogenic Cell Death and Multivalent PD‐L1 Crosslinking

Checkpoint blockade immunotherapies harness the host's own immune system to fight cancer, but only work against tumors infiltrated by swarms of preexisting T cells. Unfortunately, most cancers to date are immune‐deserted. Here, a polymer‐assisted combination of immunogenic chemotherapy and PD‐L1 degradation is reported for efficacious treatment in originally nonimmunogenic cancer. “Priming” tumors with backbone‐degradable polymer‐epirubicin conjugates elicits immunogenic cell death and fosters tumor‐specific CD8+ T cell response. Sequential treatment with a multivalent polymer‐peptide antagonist to PD‐L1 overcomes adaptive PD‐L1 enrichment following chemotherapy, biases the recycling of PD‐L1 to lysosome degradation via surface receptor crosslinking, and produces prolonged elimination of PD‐L1 rather than the transient blocking afforded by standard anti‐PD‐L1 antibodies. Together, these findings establish the polymer‐facilitated tumor targeting of immunogenic drugs and surface crosslinking of PD‐L1 as a potential new therapeutic strategy to propagate long‐term antitumor immunity, which might broaden the application of immunotherapy to immunosuppressive cancers.     

Peptide-Based Nanomaterials for Tumor Immunotherapy

With the increasing understanding of tumor immune circulation mechanisms, tumor immunotherapy including immune checkpoint blockade has become a research hotspot, which requires the development of more accurate and more efficient drugs with fewer side effects. In line with this requirement, peptides with good biocompatibility, targeting, and specificity become favorable theranostic reagents, and a series of promising candidates for tumor immunotherapy based on peptides have been developed. Additionally, the advantages of nanomaterials as drug carriers such as higher affinity have been demonstrated, providing possibilities of combination therapy. In this review, we summarize the development of peptide-based nanomaterials in tumor immunotherapy from the two aspects of functionalization and self-assembly. Furthermore, new methods for peptide screening, especially machine-learning-related strategies, is also a topic we were interested in, as this forms the basis for the construction of peptide-based platforms. Peptides provide broad prospects for tumor immunotherapy and we hope that this summary can provide insight into possible avenues for future exploration.