Modelling prostate motion for data fusion during image-guided interventions

There is growing clinical demand for image registration techniques that allow multimodal data fusion for accurate targeting of needle biopsy and ablative prostate cancer treatments. However, during procedures where transrectal ultrasound (TRUS) guidance is used, substantial gland deformation can occur due to TRUS probe pressure. In this paper, the ability of a statistical shape/motion model, trained using finite element simulations, to predict and compensate for this source of motion is investigated. Three-dimensional ultrasound images acquired on five patient prostates, before and after TRUS-probe-induced deformation, were registered using a nonrigid, surface-based method, and the accuracy of different deformation models compared. Registration using a statistical motion model was found to outperform alternative elastic deformation methods in terms of accuracy and robustness, and required substantially fewer target surface points to achieve a successful registration. The mean final target registration error (based on anatomical landmarks) using this method was 1.8 mm. We conclude that a statistical model of prostate deformation provides an accurate, rapid and robust means of predicting prostate deformation from sparse surface data, and is therefore well-suited to a number of interventional applications where there is a need for deformation compensation.     

Real-time quantification of microscale bioadhesion events in situ using imaging surface plasmon resonance (iSPR)

From macro- to nanoscales, adhesion phenomena are all-pervasive in nature yet remain poorly understood. In recent years, studies of biological adhesion mechanisms, terrestrial and marine, have provided inspiration for "biomimetic" adhesion strategies and important insights for the development of fouling-resistant materials. Although the focus of most contemporary bioadhesion research is on large organisms such as marine mussels, insects and geckos, adhesion events on the micro/nanoscale are critical to our understanding of important underlying mechanisms. Observing and quantifying adhesion at this scale is particularly relevant for the development of biomedical implants and in the prevention of marine biofouling. However, such characterization has so far been restricted by insufficient quantities of material for biochemical analysis and the limitations of contemporary imaging techniques. Here, we introduce a recently developed optical method that allows precise determination of adhesive deposition by microscale organisms in situ and in real time; a capability not before demonstrated. In this extended study we used the cypris larvae of barnacles and a combination of conventional and imaging surface plasmon resonance techniques to observe and quantify adhesive deposition onto a range of model surfaces (CH(3)-, COOH-, NH(3)-, and mPEG-terminated SAMs and a PEGMA/HEMA hydrogel). We then correlated this deposition to passive adsorption of a putatively adhesive protein from barnacles. In this way, we were able to rank surfaces in order of effectiveness for preventing barnacle cyprid exploration and demonstrate the importance of observing the natural process of adhesion, rather than predicting surface effects from a model system. As well as contributing fundamentally to the knowledge on the adhesion and adhesives of barnacle larvae, a potential target for future biomimetic glues, this method also provides a versatile technique for laboratory testing of fouling-resistant chemistries.     

Resistance of galactoside-terminated alkanethiol self-assembled monolayers to marine fouling organisms

Self-assembled monolayers (SAMs) of galactoside-terminated alkanethiols have protein-resistance properties which can be tuned via the degree of methylation [Langmuir 2005, 21, 2971-2980]. Specifically, a partially methylated compound was more resistant to nonspecific protein adsorption than the hydroxylated or fully methylated counterparts. We investigate whether this also holds true for resistance to the attachment and adhesion of a range of marine species, in order to clarify to what extent resistance to protein adsorption correlates with the more complex adhesion of fouling organisms. The partially methylated galactoside-terminated SAM was further compared to a mixed monolayer of ω-substituted methyl- and hydroxyl-terminated alkanethiols with wetting properties and surface ratio of hydroxyl to methyl groups matching that of the galactoside. The settlement (initial attachment) and adhesion strength of four model marine fouling organisms were investigated, representing both micro- and macrofoulers; two bacteria (Cobetia marina and Marinobacter hydrocarbonoclasticus), barnacle cypris larvae (Balanus amphitrite), and algal zoospores (Ulva linza). The minimum in protein adsorption onto the partially methylated galactoside surface was partly reproduced in the marine fouling assays, providing some support for a relationship between protein resistance and adhesion of marine fouling organisms. The mixed alkanethiol SAM, which was matched in wettability to the partially methylated galactoside SAM, consistently showed higher settlement (initial attachment) of test organisms than the galactoside, implying that both wettability and surface chemistry are insufficient to explain differences in fouling resistance. We suggest that differences in the structure of interfacial water may explain the variation in adhesion to these SAMs.     

Radial Blast Prediction for High Explosive Cylinders initiated at Both Ends

This paper presents experimental results for the double ended initiation of cylindrical, explosive charges. Bare cylindrical charges of PE4 (RDX/binder 88/12 %) were used with length to diameter ratios of 1/3.7 to 5.75/1 and masses of 0.25 to 0.45 kg. Pressure measurements were taken at distances of 1 to 3.5 m in the radial direction. It was found that it was possible to predict the peak overpressure in the radial direction using P=K′ M(L/D)^1/3R⁻³. M is the mass of explosive, L the length of the explosive charge, D the diameter of the explosive charge, and R the distance from the charge. For PE4, K′=2251 kPa m³ kg⁻¹ for all length to diameter ratios. The double ended initiation gives a peak overpressure 1.6 times that for single ended initiation. The impulse for double ended initiation was found to be the same as for single ended initiated charges.     

Structural, biological, and evolutionary relationships of plant food allergens sensitizing via the gastrointestinal tract

The recently completed genome sequence of the model plant species Arabidopsis has been estimated to encode over 25,000 proteins, which, on the basis of their function, can be classified into structural and metabolic (the vast majority of plant proteins), protective proteins, which defend a plant against invasion by pathogens or feeding by pests, and storage proteins, which proved a nutrient store to support germination in seeds. It is now clear that almost all plant food allergens are either protective or storage proteins. It is also becoming evident that those proteins that trigger the development of an allergic response through the gastrointestinal tract belong primarily to two large protein superfamilies: (1) The cereal prolamin superfamily, comprising three major groups of plant food allergens, the 2S albumins, lipid transfer proteins, and cereal alpha-amylase/trypsin inhibitors, which have related structures, and are stable to thermal processing and proteolysis. They include major allergens from Brazil nut, peanuts, fruits, such as peaches, and cereals, such as rice and wheat; (2) The cupin superfamily, comprising the major globulin storage proteins from a number of plant species. The globulins have been found to be allergens in plant foods, such as peanuts, soya bean, and walnut; (3) The cyteine protease C1 family, comprising the papain-like proteases from microbes, plants, and animals. This family contains two notable allergens that sensitize via the GI tract, namely actinidin from kiwi fruit and the soybean allergen, Gly m Bd 30k/P34. This study describes the properties, structures, and evolutionary relationships of these protein families, the allergens that belong to them, and discusses them in relation to the role protein structure may play in determining protein allergenicity.     

Barriers impairing mineral bioaccessibility and bioavailability in plant-based foods and the perspectives for food processing

Abstract

Plant-based foods gain more importance since they play a key role in sustainable, low-meat and healthy diets. In developing countries, these food products, especially legumes and cereals, are important staple foods. Nevertheless, the question arises on how efficient they are to deliver minerals and if it is useful to encourage their consumption to reduce the prevalence of mineral deficiencies? This review paper focuses on the discrepancy between the mineral content and the amount of minerals that can be released and absorbed from plant-based foods during human digestion which can be attributed to several inherent factors such as the presence of mineral antinutrients (phytic acid, polyphenols and dietary fiber) and physical barriers (surrounding macronutrients and cell wall). Further, this review paper summarizes the effects of different processing techniques (milling, soaking, dehulling, fermentation, germination and thermal processing) on mineral bioaccessibility and bioavailability of plant-based foods. The positive impact of these techniques mostly relies on the fact that antinutrients levels are reduced due to removal of fractions rich in antinutrients and/or due to their leaching into the processing liquid. Although processing can have a positive effect, it also can induce leaching out of minerals and a reduced mineral bioaccessibility and bioavailability.     

Pharmacologic Tumor PDL1 Depletion with Cefepime or Ceftazidime Promotes DNA Damage and Sensitivity to DNA-Damaging Agents

The interaction between tumor surface-expressed PDL1 and immune cell PD1 for the evasion of antitumor immunity is well established and is targeted by FDA-approved anti-PDL1 and anti-PD1 antibodies. Nonetheless, recent studies highlight the immunopathogenicity of tumor-intrinsic PDL1 signals that can contribute to the resistance to targeted small molecules, cytotoxic chemotherapy, and αPD1 immunotherapy. As genetic PDL1 depletion is not currently clinically tractable, we screened FDA-approved drugs to identify those that significantly deplete tumor PDL1. Among the candidates, we identified the β-lactam cephalosporin antibiotic cefepime as a tumor PDL1-depleting drug (PDD) that increases tumor DNA damage and sensitivity to DNA-damaging agents in vitro in distinct aggressive mouse and human cancer lines, including glioblastoma multiforme, ovarian cancer, bladder cancer, and melanoma. Cefepime reduced tumor PDL1 post-translationally through ubiquitination, improved DNA-damaging-agent treatment efficacy in vivo in immune-deficient and -proficient mice, activated immunogenic tumor STING signals, and phenocopied specific genetic PDL1 depletion effects. The β-lactam ring and its antibiotic properties did not appear contributory to PDL1 depletion or to these treatment effects, and the related cephalosporin ceftazidime produced similar effects. Our findings highlight the rapidly translated potential for PDDs to inhibit tumor-intrinsic PDL1 signals and improve DNA-damaging agents and immunotherapy efficacy.     

Characterization of a Potent,Selective, and Safe Inhibitor,Ac15(Az8)2, in Reversing Multidrug Resistance Mediated by Breast Cancer Resistance Protein (BCRP/ABCG2)

Overexpression of breast cancer resistance transporter (BCRP/ABCG2) in cancers has been explained for the failure of chemotherapy in clinic. Inhibition of the transport activity of BCRP during chemotherapy should reverse multidrug resistance. In this study, a triazole-bridged flavonoid dimer Ac15(Az8)₂ was identified as a potent, nontoxic, and selective BCRP inhibitor. Using BCRP-overexpressing cell lines, its EC₅₀ for reversing BCRP-mediated topotecan resistance was 3 nM in MCF7/MX100 and 72 nM in S1M180 in vitro. Mechanistic studies revealed that Ac15(Az8)₂ restored intracellular drug accumulation by inhibiting BCRP-ATPase activity and drug efflux. It did not down-regulate the cell surface BCRP level to enhance drug retention. It was not a transport substrate of BCRP and showed a non-competitive relationship with DOX in binding to BCRP. A pharmacokinetic study revealed that I.P. administration of 45 mg/kg of Ac15(Az8)₂ resulted in plasma concentration above its EC₅₀ (72 nM) for longer than 24 h. It increased the AUC of topotecan by 2-fold. In an in vivo model of BCRP-overexpressing S1M180 xenograft in Balb/c nude mice, it significantly reversed BCRP-mediated topotecan resistance and inhibited tumor growth by 40% with no serious body weight loss or death incidence. Moreover, it also increased the topotecan level in the S1M180 xenograft by 2-fold. Our results suggest that Ac15(Az8)₂ is a promising candidate for further investigation into combination therapy for treating BCRP-overexpressing cancers.     

Recent Progress in Developing a LiOH-Based Reversible Nonaqueous Lithium–Air Battery

The realization of practical nonaqueous lithium–air batteries (LABs) calls for novel strategies to address their numerous theoretical and technical challenges. LiOH formation/decomposition has recently been proposed as a promising alternative route to cycling LABs via Li₂O₂. Herein, the progress in developing LiOH-based nonaqueous LABs is reviewed. Various catalytic systems, either soluble or solid-state, that can activate a LiOH-based electrochemistry are compared in detail, with emphasis in providing an updated understanding of the oxygen reduction and evolution reactions in nonaqueous media. We identify the key factors that can switch the cell chemistry between Li₂O₂ and LiOH and highlight the debate around these routes, as well as rationalize potential causes for these opposing opinions. The identities of the reaction intermediates, activity of redox mediators and additives, location of reaction interfaces, causes of parasitic reactions, as well as the effect of CO₂ on the LiOH electrochemistry, all play a critical role in altering the relative rates of a series of interconnected reactions and all warrant further investigation.