The Mayo Clinic Florida Microdosimetric Kinetic Model of Clonogenic Survival: Application to Various Repair-Competent Rodent and Human Cell Lines

The relative biological effectiveness (RBE) calculations used during the planning of ion therapy treatments are generally based on the microdosimetric kinetic model (MKM) and the local effect model (LEM). The Mayo Clinic Florida MKM (MCF MKM) was recently developed to overcome the limitations of previous MKMs in reproducing the biological data and to eliminate the need for ion-exposed in vitro data as input for the model calculations. Since we are considering to implement the MCF MKM in clinic, this article presents (a) an extensive benchmark of the MCF MKM predictions against corresponding in vitro clonogenic survival data for 4 rodent and 10 cell lines exposed to ions from ¹H to ²³⁸U, and (b) a systematic comparison with published results of the latest version of the LEM (LEM IV). Additionally, we introduce a novel approach to derive an approximate value of the MCF MKM model parameters by knowing only the animal species and the mean number of chromosomes. The overall good agreement between MCF MKM predictions and in vitro data suggests the MCF MKM can be reliably used for the RBE calculations. In most cases, a reasonable agreement was found between the MCF MKM and the LEM IV.     

Coagulation Factor XIIIa and Activated Protein C Activate Platelets via GPVI and PAR1

Platelet and coagulation activation are highly reciprocal processes driven by multi-molecular interactions. Activated platelets secrete several coagulation factors and expose phosphatidylserine, which supports the activation of coagulation factor proteins. On the other hand, the coagulation cascade generates known ligands for platelet receptors, such as thrombin and fibrin. Coagulation factor (F)Xa, (F)XIIIa and activated protein C (APC) can also bind to platelets, but the functional consequences are unclear. Here, we investigated the effects of the activated (anti)coagulation factors on platelets, other than thrombin. Multicolor flow cytometry and aggregation experiments revealed that the ‘supernatant of (hirudin-treated) coagulated plasma’ (SCP) enhanced CRP-XL-induced platelet responses, i.e., integrin α_IIbβ₃ activation, P-selectin exposure and aggregate formation. We demonstrated that FXIIIa in combination with APC enhanced platelet activation in solution, and separately immobilized FXIIIa and APC resulted in platelet spreading. Platelet activation by FXIIIa was inhibited by molecular blockade of glycoprotein VI (GPVI) or Syk kinase. In contrast, platelet spreading on immobilized APC was inhibited by PAR1 blockade. Immobilized, but not soluble, FXIIIa and APC also enhanced in vitro adhesion and aggregation under flow. In conclusion, in coagulation, factors other than thrombin or fibrin can induce platelet activation via GPVI and PAR receptors.     

Proteomic Biomarkers of the Apnea Hypopnea Index and Obstructive Sleep Apnea: Insights into the Pathophysiology of Presence,Severity, and Treatment Response

Obstructive sleep apnea (OSA), a disease associated with excessive sleepiness and increased cardiovascular risk, affects an estimated 1 billion people worldwide. The present study examined proteomic biomarkers indicative of presence, severity, and treatment response in OSA. Participants (n = 1391) of the Stanford Technology Analytics and Genomics in Sleep study had blood collected and completed an overnight polysomnography for scoring the apnea–hypopnea index (AHI). A highly multiplexed aptamer-based array (SomaScan) was used to quantify 5000 proteins in all plasma samples. Two separate intervention-based cohorts with sleep apnea (n = 41) provided samples pre- and post-continuous/positive airway pressure (CPAP/PAP). Multivariate analyses identified 84 proteins (47 positively, 37 negatively) associated with AHI after correction for multiple testing. Of the top 15 features from a machine learning classifier for AHI ≥ 15 vs. AHI < 15 (Area Under the Curve (AUC) = 0.74), 8 were significant markers of both AHI and OSA from multivariate analyses. Exploration of pre- and post-intervention analysis identified 5 of the 84 proteins to be significantly decreased following CPAP/PAP treatment, with pathways involving endothelial function, blood coagulation, and inflammatory response. The present study identified PAI-1, tPA, and sE-Selectin as key biomarkers and suggests that endothelial dysfunction and increased coagulopathy are important consequences of OSA, which may explain the association with cardiovascular disease and stroke.     

药物纤维及其在新型给药系统中的应用

综述了制备药物纤维的材料和技术以及药物纤维在新型给药系统(DDS)中的应用。分析了目前药物纤维DDS技术存在的问题。药物纤维可分为原料型、天然纤维的后整理型、聚合物型及复合型。其制备方法主要有传统纺丝方法、静电纺丝技术、非织造布技术以及后整理技术。指出中草药纤维的DDS、智能释药纤维DDS及多药多级控释DDS是今后药物纤维DDS研究的方向。     

Coherent interaction of atoms with a beam of light confined in a light cage

Controlling coherent interaction between optical fields and quantum systems in scalable, integrated platforms is essential for quantum technologies. Miniaturise...     

Citywide: Supporting Interactive Digital Experiences Across Physical Space

The Citywide project is exploring ways in which technology can provide people with rich and engaging digital experiences as they move through physical space, including historical experiences, performances and games. This paper describes some initial results and experiences with this project based upon two prototype demonstrators. In the first, we describe an application in which a search party explores an archaeological site, uncovering enacted scenes within the virtual world that are of a historical relevance to their particular physical location. In the second, we describe a museum experience where participants explore an outdoors location, hunting for buried virtual artifacts that they then bring back to a museum for a more detailed study. Our demonstrators employ a varied set of devices, including mobile wireless interfaces for locating hotspots of virtual activity when outdoors, to give different experiences of the virtual world depending upon location, task, available equipment and accuracy of tracking. We conclude by discussing some of the potential advantages of using an underlying shared virtual world to support interactive experiences across extended physical settings.     

Activity Based Costing for Component-Based Software Development

Component-based software development is a promising set of technologies designed to move software creation from its current, labor-intensive, craft-like approach to a more modern, reuse-centered style. However, a lesson learned from previous radical software process innovations is that a strong technology alone is generally insufficient for successful adoption. In order for gains to be realized from such technologies the management practices surrounding the implementation of the new technology must also change. It is with this view that we propose the adoption of a complementary management approach called activity based costing (ABC) to allow organizations to properly account for and recognize the gains from a component-based approach. ABC enables a management environment where appropriate incentives are created for the development and reuse of software components. Data from a large software vendor who has experience with ABC in a traditional software development environment are presented, along with a chart of accounts for a modern, component-based model.     

Comparison of modified injection molding and conventional machining in biodegradable behavior of perforated cannulated magnesium hip stents

In this study,perforated cannulated magnesium(Mg)hip stents were fabricated via modified Mg injection molding and conventional machining,respectively.Additionally,the stent canal was filled with paraffin to simulate injection of biomaterials.The microstructure,mechanical performance,corrosion behavior,and biocompatibility were comparably studied.Scanning electron microscopy(SEM)and energy dispersive spectroscopy(EDS)showed higher affinity of interstitial element such as oxygen and carbon as consequences of routine molding process.After immersion in SBF,machining stents showed reduced degradation rate and increased deposition of calcium phosphate compared to molding stents.Corrosion resistance was improved via paraffin-filling.Consistently,the hemolysis and in vitro osteoblast cell culture models showed favourable biocompatibility in machining stents compared to molding ones,which was improved by paraffin-filling treatment as well.These results implied that the feasibility of the prepared machining stents as the potential in vivo orthopaedic application where slower degradation is required,which could be enhanced by designing canal-filling injection of biomaterials as well.     

Passive samplers provide a better prediction of PAH bioaccumulation in earthworms and plant roots than exhaustive, mild solvent, and cyclodextrin extractions

A number of extraction methods have been developed to assess polycyclic aromatic hydrocarbon (PAH) bioavailability in soils. As these methods are rarely tested in a comparative manner, against different test organisms, and using field-contaminated soils, it is unclear which method gives the most accurate measure of the actual soil ecosystem exposure. In this study, PAH bioavailability was assessed in ten field-contaminated soils by using exhaustive acetone/hexane extractions, mild solvent (butanol) extractions, cyclodextrin extractions, and two passive sampling methods; solid phase micro extraction (SPME) and polyoxymethylene solid phase extraction (POM-SPE). Results were compared to actual PAH bioaccumulation in earthworms (Eisenia fetida) and rye grass (Lolium multiflorum) roots. Exhaustive, mild solvent and cyclodextrin extractions consistently overpredicted biotic concentrations by a factor of 10-10?000 and therefore seem inappropriate for predicting PAH bioaccumulation in field contaminated soils. In contrast, passive samplers generally predicted PAH concentrations in earthworms within a factor of 10, although correlations between predicted and measured concentrations were considerably scattered. The same applied to the plant data, where passive samplers also tended to underpredict root concentrations. These results indicate the potential of passive samplers to predict PAH bioaccumulation, yet call for comparative studies between passive samplers and further research on plant bioavailability.