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We investigate and model a method for producing entanglement between two spatially separated Bose-Einstein condensates (BECs). In our approach, a spin-polarized BEC is squeezed using a (Sz)2 interaction, then are split into two separate clouds. After the split, we consider that the particle number in each cloud collapses to a fixed number. We show that this procedure is equivalent to applying an interaction corresponding to squeezing each cloud individually plus an entangling operation. We analyze the system's inter-well entanglement properties and show that it can be detected using correlation-based entanglement criteria. The nature of the states is illustrated by Wigner functions and have the form of a correlated squeezed state. The conditional Wigner function shows high degrees of non-classicality for dimensionless squeezing times beyond 1 N , where N is the number of particles per BEC.

Cancer causes the second-highest rate of death world-wide. A major shortcoming inherent in most of anticancer drugs is their lack of tumor selectivity. Nanodrugs for cancer therapy administered intravenously escape renal clearance, are unable to penetrate through tight endothelial junctions of normal blood vessels and remain at a high level in plasma. Over time, the concentration of nanodrugs builds up in tumors due to the EPR effect, reaching several times higher than that of plasma due to the lack of lymphatic drainage. This review will address in detail the progress and prospects of tumor-targeting via EPR effect for cancer therapy.

Following its discovery more than 30 years ago, the enhanced permeability and retention (EPR) effect has become the guiding principle for cancer nanomedicine development. Over the years, the tumor-targeted drug delivery field has made significant progress, as evidenced by the approval of several nanomedicinal anticancer drugs. Recently, however, the existence and the extent of the EPR effect - particularly in patients - have become the focus of intense debate. This is partially due to the disbalance between the huge number of preclinical cancer nanomedicine papers and relatively small number of cancer nanomedicine drug products reaching the market. To move the field forward, we have to improve our understanding of the EPR effect, of its cancer type-specific pathophysiology, of nanomedicine interactions with the heterogeneous tumor microenvironment, of nanomedicine behavior in the body, and of translational aspects that specifically complicate nanomedicinal drug development. In this virtual special issue, 24 research articles and reviews discussing different aspects of the EPR effect and cancer nanomedicine are collected, together providing a comprehensive and complete overview of the current state-of-the-art and future directions in tumor-targeted drug delivery.

Quartz (trigonal, low-temperature α-quartz) is the most important polymorph of the silica (SiO 2 ) group and one of the purest minerals in the Earth crust. The mineralogy and mineral chemistry of quartz are determined mainly by its defect structure. Certain point defects, dislocations and micro-inclusions can be incorporated into quartz during crystallisation under various thermodynamic conditions and by secondary processes such as alteration, irradiation, diagenesis or metamorphism. The resulting real structure is a fingerprint of the specific physicochemical environment of quartz formation and also determines the quality and applications of SiO 2 raw materials. Point defects in quartz can be related to imperfections associated with silicon or oxygen vacancies (intrinsic defects), to different types of displaced atoms, and/or to the incorporation of foreign ions in lattice sites and interstitial positions (extrinsic defects). Due to mismatch in charges and ionic radii only a limited number of ions can substitute for Si 4+ in the crystal lattice or can be incorporated in interstitial positions. Therefore, most impurity elements in quartz are present at concentrations below 1 ppm. The structural incorporation in a regular Si 4+ lattice site has been proven for Al 3+ , Ga 3+ , Fe 3+ , B 3+ , Ge 4+ , Ti 4+ , P 5+ and H + , of which Al 3+ is by far the most common and typically the most abundant. Unambiguous detection and characterisation of defect structures in quartz are a technical challenge and can only be successfully realised by a combination of advanced analytical methods such as electron paramagnetic resonance (EPR) spectroscopy, cathodoluminescence (CL) microscopy and spectroscopy as well as spatially resolved trace-element analysis such as laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and secondary-ion mass spectrometry (SIMS). The present paper presents a review of the state-of-the-art knowledge concerning the mineralogy and mineral-chemistry of quartz and illustrates important geological implications of the properties of quartz.

For more than three decades, enhanced permeability and retention (EPR)-effect-based nanomedicines have received considerable attention for tumor-selective treatment of solid tumors. However, treatment of advanced cancers remains a huge challenge in clinical situations because of occluded or embolized tumor blood vessels, which lead to so-called heterogeneity of the EPR effect. We previously developed a method to restore impaired blood flow in blood vessels by using nitric oxide donors and other agents called EPR-effect enhancers. Here, we show that two novel EPR-effect enhancers—isosorbide dinitrate (ISDN, Nitrol®) and sildenafil citrate—strongly potentiated delivery of three macromolecular drugs to tumors: a complex of poly(styrene-co-maleic acid) (SMA) and cisplatin, named Smaplatin® (chemotherapy); poly(N-(2-hydroxypropyl)methacrylamide) polymer-conjugated zinc protoporphyrin (photodynamic therapy and imaging); and SMA glucosamine-conjugated boric acid complex (boron neutron capture therapy). We tested these nanodrugs in mice with advanced C26 tumors. When these nanomedicines were administered together with ISDN or sildenafil, tumor delivery and thus positive therapeutic results increased two- to four-fold in tumors with diameters of 15 mm or more. These results confirmed the rationale for using EPR-effect enhancers to restore tumor blood flow. In conclusion, all EPR-effect enhancers tested showed great potential for application in cancer therapy.

Electron paramagnetic resonance (EPR) is an accurate and efficient technique to probe unpaired electrons in many applications across materials science, chemistry, and biology. Dynamic processes are investigated using EPR; however, these applications are limited by the use of resonator-based spectrometers such that the entire process must be confined to the resonator. The EPR-on-a-chip (EPRoC) device circumvents this limitation by integrating the entire EPR spectrometer into a single microchip. In this approach, the coil of a voltage-controlled oscillator (VCO) is used as the microwave source and detector simultaneously, operating under a protective coating such that the device may be placed in the sample solution directly. Additionally, improvements in sensitivity via rapid scan EPR (RS-EPR/RS-EPRoC) increase the accessible applications where SNR per measurement time is the fundamental limit. The herein reported device combines a dipstick EPRoC sensor with the enhanced sensitivity of frequency-swept frequency modulated rapid scan to measure triarylmethyl (trityl, Ox071) oxygen-sensitive probes dissolved in aqueous solutions. EPR spectra of Ox071 solutions were recorded using the RS-EPRoC sensor while varying the oxygen concentration of the solution between normal atmosphere and after purging the solution with nitrogen gas. We demonstrate that EPRoC may be employed to monitor dissolved oxygen in fluid solution in an online fashion.

In this study, an apple polysaccharide (AP) that exhibited a gelatin-like gelation behavior has been reported, with the gelation mechanism being further revealed. It was found that a suitable amount of Ca[sup.2+] addition (4.5 mmol·L[sup.−1]) induced the formation of AP gels at 0.5% (w/v) polymer concentration in a wide pH range (3.0–8.0) by holding the polysaccharide solution at 4 °C. However, no gel was formed in the absence of Ca[sup.2+]. Meanwhile, all gels melted around 33 °C upon reheating, and the change in pH did not significantly affect the formation and melting processes of the AP gels. Furthermore, ITC and EPR measurements indicated no detectable binding of Ca[sup.2+] to AP chains. Thus, the gelation mechanism was explained as Ca[sup.2+]-mediated electrostatic screening, whose presence facilitated AP chain–chain association and ultimately triggered network formation. Our results suggested that AP may exhibit high potential as a possible gelatin substitute in food production.

In 1979, development of the first polymer drug SMANCS [styrene-co-maleic acid (SMA) copolymer conjugated to neocarzinostatin (NCS)] by Maeda and colleagues was a breakthrough in the cancer field. When SMANCS was administered to mice, drug accumulation in tumors was markedly increased compared with accumulation of the parental drug NCS. This momentous result led to discovery of the enhanced permeability and retention effect (EPR effect) in 1986. Later, the EPR effect became known worldwide, especially in nanomedicine, and is still believed to be a universal mechanism for tumor-selective accumulation of nanomedicines. Some research groups recently characterized the EPR effect as a controversial concept and stated that it has not been fully demonstrated in clinical settings, but this erroneous belief is due to non-standard drug design and use of inappropriate tumor models in investigations. Many research groups recently provided solid evidence of the EPR effect in human cancers (e.g., renal and breast), with significant diversity and heterogeneity in various patients. In this review, we focus on the dynamics of the EPR effect and restoring tumor blood flow by using EPR effect enhancers. We also discuss new applications of EPR-based nanomedicine in boron neutron capture therapy and photodynamic therapy for solid tumors.

The twin unit EPR construction at Hinkley Point C is the first nuclear new build project to be undertaken in the UK in a generation. Moreover, it is now the country’s only new reactor project still in progress. The station’s two 1650 MWe plants [1] will complement the UK’s decarbonisedm energy mix with addition of approximately 7% of the current national requirement. In 2019, less than three years from the final investment decision, the ‘J0’ milestone was reached. This represents the end of the preparatory works, including all the common raft nuclear island concrete for Unit 1, enabling the upwards erection of the reactor containment and other support buildings. In addition to this, important milestones such as launch of the first tunnel boring machine, to tunnel the Unit 1 sea-water intake pipe have all been achieved. Over the coming years, the project will need to evolve in order to meet the increasing complexity and multi-organisation scope, which will present a challenging delivery environment. In order to support this, a UK-based Design Authority works on review, verification and acceptance of the HPC design including its UK specificities. This allows NNB, as licensee, to own its design and prepare the pre-commissioning safety case and operational strategies, defensible to the relevant UK regulators. As an example, this paper presents the roles and responsibilities in the Reactor Technology Team. This small, flexible team is involved in technical oversight of all aspects of the fuel & core design, through normal operations, anticipated and design-basis faults, severe accidents and radiological consequence estimation.

Nanomaterial-based drug delivery systems (NBDDS) are widely used to improve the safety and therapeutic efficacy of encapsulated drugs due to their unique physicochemical and biological properties. By combining therapeutic drugs with nanoparticles using rational targeting pathways, nano-targeted delivery systems were created to overcome the main drawbacks of conventional drug treatment, including insufficient stability and solubility, lack of transmembrane transport, short circulation time, and undesirable toxic effects. Herein, we reviewed the recent developments in different targeting design strategies and therapeutic approaches employing various nanomaterial-based systems. We also discussed the challenges and perspectives of smart systems in precisely targeting different intravascular and extravascular diseases.