Dynamic optimal experimental design yields marginal improvement over steady‐state results for computational maximisation of regulatory T‐cell induction in ex vivo culture

The isolation of T cells, followed by differentiation into Regulatory T cells (Tregs), and re‐transplantation into the body has been proposed as a therapeutic option for inflammatory bowel disease. A key requirement for making this a viable therapeutic option is the generation of a large population of Tregs. However, cytokines in the local microenvironment can impact the yield of Tregs during differentiation. As such, experimental design is an essential part of evaluating the importance of different cytokine concentrations for Treg differentiation. However, currently only single, constant concentrations of the cytokines have been investigated. This work addresses this point by performing experimental design in silico which seeks to maximize the predicted induction of Tregs relative to Th17 cells, by selecting an optimal input function for the concentrations of TGF‐β, IL‐2, IL‐6, and IL‐23. While this approach sounds promising, the results show that only marginal improvements in the concentration of Tregs can be achieved for dynamic cytokine profiles as compared to optimal constant concentrations. Since constant concentrations are easier to implement in experiments, it is recommended for this particular system to keep the concentrations constant where IL‐6 should be kept low and high concentrations of TGF‐β, IL‐2, and IL‐23 should be used.Inspec keywords: patient treatment, molecular biophysics, proteins, cellular biophysics, diseasesOther keywords: Tregs relative, optimal input function, dynamic cytokine profiles, optimal constant concentrations, IL‐23, computational maximisation, regulatory T‐cell induction, inflammatory bowel disease, viable therapeutic option, local microenvironment, Treg differentiation, single concentrations, predicted induction, dynamic optimal experimental design, interleukin‐2, IL‐6, transforming growth factor‐β     

Microalgae-Based Biohybrid Microrobot for Accelerated Diabetic Wound Healing

A variety of wound healing platforms have been proposed to alleviate the hypoxic condition and/or to modulate the immune responses for the treatment of chronic wounds in diabetes. However, these platforms with the passive diffusion of therapeutic agents through the blood clot result in the relatively low delivery efficiency into the deep wound site. Here, a microalgae-based biohybrid microrobot for accelerated diabetic wound healing is developed. The biohybrid microrobot autonomously moves at velocity of 33.3 µm s⁻¹ and generates oxygen for the alleviation of hypoxic condition. In addition, the microrobot efficiently bound with inflammatory chemokines of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) for modulating the immune responses. The enhanced penetration of microrobot is corroborated by measuring fibrin clots in biomimetic wound using microfluidic devices and the enhanced retention of microrobot is confirmed in the real wounded mouse skin tissue. After deposition on the chronic wound in diabetic mice without wound dressing, the wounds treated with microrobots are completely healed after 9 days with the significant decrease of inflammatory cytokines below 31% of the control level and the upregulated angiogenesis above 20 times of CD31⁺ cells. These results confirm the feasibility of microrobots as a next-generation platform for diabetic wound healing.     

Wavelet transforms for detecting microcalcifications in mammograms

Clusters of fine, granular microcalcifications in mammograms may be an early sign of disease. Individual grains are difficult to detect and segment due to size and shape variability and because the background mammogram texture is typically inhomogeneous. The authors develop a 2-stage method based on wavelet transforms for detecting and segmenting calcifications. The first stage is based on an undecimated wavelet transform, which is simply the conventional filter bank implementation without downsampling, so that the low-low (LL), low-high (LH), high-low (HL), and high-high (HH) sub-bands remain at full size. Detection takes place in HH and the combination LH+HL. Four octaves are computed with 2 inter-octave voices for finer scale resolution. By appropriate selection of the wavelet basis the detection of microcalcifications in the relevant size range can be nearly optimized. In fact, the filters which transform the input image into HH and LH+HL are closely related to prewhitening matched filters for detecting Gaussian objects (idealized microcalcifications) in 2 common forms of Markov (background) noise. The second stage is designed to overcome the limitations of the simplistic Gaussian assumption and provides an accurate segmentation of calcification boundaries. Detected pixel sites in HH and LH+HL are dilated then weighted before computing the inverse wavelet transform. Individual microcalcifications are greatly enhanced in the output image, to the point where straightforward thresholding can be applied to segment them. FROG curves are computed from tests using a freely distributed database of digitized mammograms.     

Refining the level for anticipated hepatotoxicity in acetaminophen poisoning

Treatment of an acetaminophen overdose with N-acetyl cysteine usually is based on the position of the 4-h acetaminophen (APAP) level on the Rumack-Matthew nomogram; however, there is disagreement on the level at which clinically relevant hepatotoxicity occurs. A retrospective review of all acute adult formulation APAP exposures reported to our poison center between 1986 and 1993 was performed and cases corresponding to the "possible risk or toxicity" range on the nomogram were identified. Our current poison center protocol for APAP poisoning does not recommend treatment with N-acetylcysteine (NAC) in low-risk patients if the 4-h serum APAP level or the extrapolated equivalent falls within the possible toxicity range on the nomogram. Seventeen cases met the inclusion criteria for the study and received no NAC; six additional patients met inclusion criteria but received one or two doses of NAC before therapy was discontinued. No patients in either group demonstrated clinical evidence of hepatotoxicity. This pilot study suggests that patients with no risk factors and APAP levels in the "possible risk" range may not require NAC therapy.     

GPU-based real-time approximation of the ablation zone for radiofrequency ablation

Percutaneous radiofrequency ablation (RFA) is becoming a standard minimally invasive clinical procedure for the treatment of liver tumors. However, planning the applicator placement such that the malignant tissue is completely destroyed, is a demanding task that requires considerable experience. In this work, we present a fast GPU-based real-time approximation of the ablation zone incorporating the cooling effect of liver vessels. Weighted distance fields of varying RF applicator types are derived from complex numerical simulations to allow a fast estimation of the ablation zone. Furthermore, the heat-sink effect of the cooling blood flow close to the applicator's electrode is estimated by means of a preprocessed thermal equilibrium representation of the liver parenchyma and blood vessels. Utilizing the graphics card, the weighted distance field incorporating the cooling blood flow is calculated using a modular shader framework, which facilitates the real-time visualization of the ablation zone in projected slice views and in volume rendering. The proposed methods are integrated in our software assistant prototype for planning RFA therapy. The software allows the physician to interactively place virtual RF applicator models. The real-time visualization of the corresponding approximated ablation zone facilitates interactive evaluation of the tumor coverage in order to optimize the applicator's placement such that all cancer cells are destroyed by the ablation.     

Intelligent security and access control framework for service-oriented architecture

One of the most significant difficulties with developing Service-Oriented Architecture (SOA) involves meeting its security challenges, since the responsibilities of SOA security are based on both the service providers and the consumers. In recent years, many solutions to these challenges have been implemented, such as the Web Services Security Standards, including WS-Security and WS-Policy. However, those standards are insufficient for the new generation of Web technologies, including Web 2.0 applications. In this research, we propose an intelligent SOA security framework by introducing its two most promising services: the Authentication and Security Service (NSS), and the Authorization Service (AS). The suggested autonomic and reusable services are constructed as an extension of WS-¹ security standards, with the addition of intelligent mining techniques, in order to improve performance and effectiveness. In this research, we apply three different mining techniques: the Association Rules, which helps to predict attacks, the Online Analytical Processing (OLAP) Cube, for authorization, and clustering mining algorithms, which facilitate access control rights representation and automation. Furthermore, a case study is explored to depict the behavior of the proposed services inside an SOA business environment. We believe that this work is a significant step towards achieving dynamic SOA security that automatically controls the access to new versions of Web applications, including analyzing and dropping suspicious SOAP messages and automatically managing authorization roles.     

Characterization of terrestrial water dynamics in the Congo Basin using GRACE and satellite radar altimetry

The Congo Basin is the world's third largest in size (~ 3.7 million km²), and second only to the Amazon River in discharge (~ 40,200 m³ s^− 1 annual average). However, the hydrological dynamics of seasonally flooded wetlands and floodplains remains poorly quantified. Here, we separate the Congo wetland into four 3° × 3° regions, and use remote sensing measurements (i.e., GRACE, satellite radar altimeter, GPCP, JERS-1, SRTM, and MODIS) to estimate the amounts of water filling and draining from the Congo wetland, and to determine the source of the water. We find that the amount of water annually filling and draining the Congo wetlands is 111 km³, which is about one-third the size of the water volumes found on the mainstem Amazon floodplain. Based on amplitude comparisons among the water volume changes and timing comparisons among their fluxes, we conclude that the local upland runoff is the main source of the Congo wetland water, not the fluvial process of river-floodplain water exchange as in the Amazon. Our hydraulic analysis using altimeter measurements also supports our conclusion by demonstrating that water surface elevations in the wetlands are consistently higher than the adjacent river water levels. Our research highlights differences in the hydrology and hydrodynamics between the Congo wetland and the mainstem Amazon floodplain.     

A lumped-parameter model to investigate the effect of plantar pressure on arterial blood flow in a diabetic foot

This paper presents a lumped-parameter model for the big-toe region that investigates the effect of plantar pressure on the diameter of the blood vessels, specifically the arteries, in the presence of arterial and/or tissue changes. The model developed in this paper uses a multi-domain energy system approach to develop the lumped-parameter differential equations. Blood flow is modelled as fluidic flow through compliant pipes that have inertia, stiffness, and damping. The tissue material is treated as a soft compliant material that transmits the external force to the blood vessels. Conclusions have been drawn to show the effect of plantar pressure, tissue damage, and their combination on the diameter of the blood vessels. The principles used here can be used to model the entire foot and the model used to investigate the effect of plantar pressure, tissue damage, and arterial changes on different parts of the foot. The work presented here may also have applications in other vascular diseases.     

Collection and transfusion of blood and blood components in the United States, 1989

A poor response to L-DOPA in addition to parkinsonian, cerebellar, and autonomic signs is commonly regarded as indicative of clinical multiple system atrophy (MSA). We compared the motor response to a single oral administration of 250 mg L-DOPA/25 mg carbidopa in eight MSA patients and eight Parkinson's disease (PD) patients with the "on-off" phenomenon, evaluating L-DOPA peripheral pharmacokinetics. Motor response was consistently good in all PD patients, but only four MSA patients had a (moderate) response. Pharmacokinetic parameters did not differ between the groups. The varying extent of putaminal damage could be responsible for the differing motor response to L-DOPA in MSA patients.