A multiple-network poroelastic model for biological systems and application to subject-specific modelling of cerebral fluid transport

Biological tissue can be viewed as porous, permeable and deformable media infiltrated by fluids, such as blood and interstitial fluid. A finite element model has been developed based on the multiple-network poroelastic theory to investigate transport phenomenon in such biological systems. The governing equations and boundary conditions are adapted for the cerebral environment as an example. The numerical model is verified against analytical solutions of classical consolidation problems and validated using experimental data of infusion tests. It is then applied to three-dimensional subject-specific modelling of brain, including anatomically realistic geometry, personalised permeability map and arterial blood supply to the brain. Numerical results of smoking and non-smoking subjects show hypoperfusion in the brains of smoking subjects, which also demonstrate that the numerical model is capable of capturing spatio-temporal fluid transport in biological systems across different scales

Exploring neurodegenerative disorders using a novel integrated model of cerebral transport: Initial results

The neurovascular unit (NVU) underlines the complex and symbiotic relationship between brain cells and the cerebral vasculature, and dictates the need to consider both neurodegenerative and cerebrovascular diseases under the same mechanistic umbrella. Importantly, unlike peripheral organs, the brain was thought not to contain a dedicated lymphatics system. The glymphatic system concept (a portmanteau of glia and lymphatic) has further emphasized the importance of cerebrospinal fluid transport and emphasized its role as a mechanism for waste removal from the central nervous system. In this work, we outline a novel multiporoelastic solver which is embedded within a high precision, subject specific workflow that allows for the co-existence of a multitude of interconnected compartments with varying properties (multiple-network poroelastic theory, or MPET), that allow for the physiologically accurate representation of perfused brain tissue. This novel numerical template is based on a six-compartment MPET system (6-MPET) and is implemented through an in-house finite element code. The latter utilises the specificity of a high throughput imaging pipeline (which has been extended to incorporate the regional variation of mechanical properties) and blood flow variability model developed as part of the VPH-DARE@IT research platform. To exemplify the capability of this large-scale consolidated pipeline, a cognitively healthy subject is used to acquire novel, biomechanistically inspired biomarkers relating to primary and derivative variables of the 6-MPET system. These biomarkers are shown to capture the sophisticated nature of the NVU and the glymphatic system, paving the way for a potential route in deconvoluting the complexity associated with the likely interdependence of neurodegenerative and cerebrovascular diseases. The present study is the first, to the best of our knowledge, that casts and implements the 6-MPET equations in a 3D anatomically accurate brain geometry

A fully dynamic multi-compartmental poroelastic system: Application to aqueductal stenosis

This study proposes the implementation of a fully dynamic four-network poroelastic model which is underpinned by multiple-network poroelastic theory (MPET), in order to account for the effects of varying stages of aqueductal stenosis and atresia during acute hydrocephalus. The innovation of the fully dynamic MPET implementation is that it avoids the commonplace assumption of quasi-steady behaviour; instead, it incorporates all transient terms in the casting of the equations and in the numerical solution of the resulting discrete system. It was observed that the application of mild stenosis allows for a constant value of amalgamated ventricular displacement in under 2.4 h, whereas the application of a severe stenosis delays this settlement to approximately 10 h. A completely blocked aqueduct does not show a clear sign of reaching a steady ventricular displacement after 24 h. The increasing ventricular pressure (complemented with ventriculomegaly) during severe stenosis is causing the trans-parenchymal tissue region to respond, and this coping mechanism is most attenuated at the regions closest to the skull and the ventricles. After 9 h, the parenchymal tissue shows to be coping well with the additional pressure burden, since both ventriculomegaly and ventricular CSF (cerebrospinal fluid) pressure show small increases between 9 and 24 h. Localised swelling in the periventricular region could also be observed through CSF fluid content, whilst dilation results showed stretch and compression of cortical tissue adjacent to the ventricles and skull

MRI detection of peritoneal adhesion with dialysate enhancement

This study investigated the use of clinical peritoneal dialysis fluid (dialysate) as a peritoneal contrast agent to visualize peritoneal adhesions in rats at 7 Tesla. Intraperitoneal injection of dialysate (~0.1 mL/g) allowed the MR detection of peritoneal adhesions that were surgically induced in all rats studied (N = 6). MR measurements of adhesion surface areas correlated well with the postmortem estimations (R = 0.99). T1 and T2 values of undiluted dialysate were found to be 3017.5¡Ó35.3 ms and 108.4¡Ó2.0 ms, respectively. These findings demonstrated dialysate-enhanced MRI as a potentially valuable technique in clinical detection and evaluation of post-surgical peritoneal adhesion and to monitor therapeutic interventions (i.e., against peritoneal adhesion) in future preclinical research.published_or_final_versio

Monolithic high-temperature superconducting heterodyne Josephson frequency down-converter

A monolithic microwave integrated circuit (MMIC) frequency down-converter based on a compact high-T c superconducting (HTS) device is demonstrated. The on-chip integrated HTS down-converter consists of a 7-9 GHz bandpass filter for RF input, a lowpass filter for intermediate frequency output, and a self-pumped Josephson heterodyne mixer. All the above passive and active components are fabricated on a single 10 mm × 20 mm chip of YBa 2Cu 3O 7-x film on MgO substrate. Characterization of this MMIC HTS down-converter in terms of frequency response, conversion gain, frequency-tuneability, bias dependence, dynamic range, linearity, and intrinsic noise are presented in this paper. © 2012 Crown

Concept of a Self-Learning Workplace Cell for Worker Assistance While Collaboration with a Robot Within the Self-Adapting-Production-Planning-System

For some time, the focus of past research on industrial workplace designs has been the optimization of processes from the technological point of view. Since human workers have to work within this environment the design process must regard Human Factor needs. The operators are under additional stress due to the range of high dynamic processes and due to the integration of robots and autonomous operating machines. There have been few studies on how Human Factors influence the design of workplaces for Human-Robot Collaboration (HRC). Furthermore, a comprehensive, systematic and human-centred design solution for industrial workplaces particularly considering Human Factor needs within HRC is widely uncertain and a specific application with reference to production workplaces is missing. The research findings described in this paper aim the optimization of workplaces for manual production and maintenance processes with respect to the workers within HRC. In order to increase the acceptance of integration of human-robot teams, the concept of the Assisting-Industrial-Workplace-System (AIWS) was developed. As a flexible hybrid cell for HRC integrated into a Self-Adapting-Production-Planning-System (SAPPS) assists the worker while interaction

Targeting Btk/Etk of prostate cancer cells by a novel dual inhibitor.

Btk and Etk/BMX are Tec-family non-receptor tyrosine kinases. Btk has previously been reported to be expressed primarily in B cells and has an important role in immune responses and B-cell malignancies. Etk has been shown previously to provide a strong survival and metastasis signal in human prostate cancer cells, and to confer androgen independence and drug resistance. While the role of Etk in prostate carcinogenesis is well established, the functions of Btk in prostate cancer have never been investigated, likely due to the perception that Btk is a hematopoietic, but not epithelial, kinase. Herein, we found that Btk is overexpressed in prostate cancer tissues and prostate cancer cells. The level of Btk in prostate cancer tissues correlates with cancer grades. Knockdown of Btk expression selectively inhibits the growth of prostate cancer cells, but not that of the normal prostate epithelial cells, which express very little Btk. Dual inhibition of Btk and Etk has an additive inhibitory effect on prostate cancer cell growth. To explore Btk and Etk as targets for prostate cancer, we developed a small molecule dual inhibitor of Btk and Etk, CTN06. Treatment of PC3 and other prostate cancer cells, but not immortalized prostate epithelial cells with CTN06 resulted in effective cell killing, accompanied by the attenuation of Btk/Etk signals. The killing effect of CTN06 is more potent than that of commonly used inhibitors against Src, Raf/VEGFR and EGFR. CTN06 induces apoptosis as well as autophagy in human prostate cancer cells, and is a chemo-sensitizer for docetaxel (DTX), a standard of care for metastatic prostate cancer patients. CTN06 also impeded the migration of human prostate cancer cells based on a 'wound healing' assay. The anti-cancer effect of CTN06 was further validated in vivo in a PC3 xenograft mouse model

Testing and comparing two self-care-related instruments among older Chinese adults

Objectives The study aimed to test and compare the reliability and validity, including sensitivity and specificity of the two self-care-related instruments, the Self-care Ability Scale for the Elderly (SASE), and the Appraisal of Self-care Agency Scale-Revised (ASAS-R), among older adults in the Chinese context. Methods A cross-sectional design was used to conduct this study. The sample consisted of 1152 older adults. Data were collected by a questionnaire including the Chinese version of SASE (SASE-CHI), the Chinese version of ASAS-R (ASAS-R-CHI) and the Exercise of Self-Care Agency scale (ESCA). Homogeneity and stability, content, construct and concurrent validity, and sensitivity and specificity were assessed. Results The Cronbach's alpha (α) of SASE-CHI was 0.89, the item-to-total correlations ranged from r = 0.15 to r = 0.81, and the test-retest correlation coefficient (intra-class correlation coefficient, ICC) was 0.99 (95% CI, 0.99±1.00; P<0.001). The Cronbach's α of ASAS-R-CHI was 0.78, the item-to-total correlations ranged from r = 0.20 to r = 0.65, and the test-retest ICC was 0.95 (95% CI, 0.92±0.96; P<0.001). The content validity index (CVI) of SASE-CHI and ASAS-R-CHI was 0.96 and 0.97, respectively. The findings of exploratory and confirmatory factor analyses (EFA and CFA) confirmed a good construct validity of SASE-CHI and ASAS-R-CHI. The Pearson's rank correlation coefficients, as a measure of concurrent validity, between total score of SASE-CHI and ESCA and ASAS-R-CHI and ESCA were assessed to 0.65 (P<0.001) and 0.62 (P<0.001), respectively. Regarding ESCA as the criterion, the area under the receiver operator characteristic (ROC) curve for the cut-point of SASE-CHI and ASAS-R-CHI were 0.93 (95% CI, 0.91±0.94) and 0.83 (95% CI, 0.80±0.86), respectively. Conclusion There is no significant difference between the two instruments. Each has its own characteristics, but SASE-CHI is more suitable for older adults. The key point is that the users can choose the most appropriate scale according to the specific situation.publishedVersionNivå

Interface Engineering for Atomic Layer Deposited Alumina Gate Dielectric on SiGe Substrates.

Optimization of the interface between high-k dielectrics and SiGe substrates is a challenging topic due to the complexity arising from the coexistence of Si and Ge interfacial oxides. Defective high-k/SiGe interfaces limit future applications of SiGe as a channel material for electronic devices. In this paper, we identify the surface layer structure of as-received SiGe and Al2O3/SiGe structures based on soft and hard X-ray photoelectron spectroscopy. As-received SiGe substrates have native SiOx/GeOx surface layers, where the GeOx-rich layer is beneath a SiOx-rich surface. Silicon oxide regrows on the SiGe surface during Al2O3 atomic layer deposition, and both SiOx and GeOx regrow during forming gas anneal in the presence of a Pt gate metal. The resulting mixed SiOx-GeOx interface layer causes large interface trap densities (Dit) due to distorted Ge-O bonds across the interface. In contrast, we observe that oxygen-scavenging Al top gates decompose the underlying SiOx/GeOx, in a selective fashion, leaving an ultrathin SiOx interfacial layer that exhibits dramatically reduced Dit

Interface Engineering for Atomic Layer Deposited Alumina Gate Dielectric on SiGe Substrates.

Optimization of the interface between high-k dielectrics and SiGe substrates is a challenging topic due to the complexity arising from the coexistence of Si and Ge interfacial oxides. Defective high-k/SiGe interfaces limit future applications of SiGe as a channel material for electronic devices. In this paper, we identify the surface layer structure of as-received SiGe and Al2O3/SiGe structures based on soft and hard X-ray photoelectron spectroscopy. As-received SiGe substrates have native SiOx/GeOx surface layers, where the GeOx-rich layer is beneath a SiOx-rich surface. Silicon oxide regrows on the SiGe surface during Al2O3 atomic layer deposition, and both SiOx and GeOx regrow during forming gas anneal in the presence of a Pt gate metal. The resulting mixed SiOx-GeOx interface layer causes large interface trap densities (Dit) due to distorted Ge-O bonds across the interface. In contrast, we observe that oxygen-scavenging Al top gates decompose the underlying SiOx/GeOx, in a selective fashion, leaving an ultrathin SiOx interfacial layer that exhibits dramatically reduced Dit