Dynamic high-resolution computer simulation of electrophoretic enantiomer separations with neutral cyclodextrins as chiral selectors.

GENTRANS, a comprehensive one-dimensional dynamic simulator for electrophoretic separations and transport, was extended for handling electrokinetic chiral separations with a neutral ligand. The code can be employed to study the 1:1 interaction of monovalent weak and strong acids and bases with a single monovalent weak or strong acid or base additive, including a neutral cyclodextrin, under real experimental conditions. It is a tool to investigate the dynamics of chiral separations and to provide insight into the buffer systems used in chiral capillary zone electrophoresis (CZE) and chiral isotachophoresis. Analyte stacking across conductivity and buffer additive gradients, changes of additive concentration, buffer component concentration, pH, and conductivity across migrating sample zones and peaks, and the formation and migration of system peaks can thereby be investigated in a hitherto inaccessible way. For model systems with charged weak bases and neutral modified β-cyclodextrins at acidic pH, for which complexation constants, ionic mobilities, and mobilities of selector-analyte complexes have been determined by CZE, simulated and experimentally determined electropherograms and isotachopherograms are shown to be in good agreement. Simulation data reveal that CZE separations of cationic enantiomers performed in phosphate buffers at low pH occur behind a fast cationic migrating system peak that has a small impact on the buffer composition under which enantiomeric separation takes place.

[Computer tomographic differentiation of intrathoracic neoplasms and inflammation in the dog].

The purpose of this study was to elaborate on the advantages and limits of computed tomography (CT) in the differentiation of thoracic lesions, in particular neoplasias. In the course of the investigation CT-scans of the thorax of 31 dogs with lesions in the area of the lungs or mediastinum were evaluated. The lesions were rated by morphology, distribution pattern, attenuation values and contrast-enhancement. Biopsies or the whole body underwent a pathohistological examination. Of the 31 dogs 17 had neoplastic and 14 had inflammatory lesions in the thoracic region. With help of the CT, the exact localisations of the different lesions was possible in most cases. Due to their characteristic morphologies, distribution patterns and attenuation values the differentiation between inflammatory and neoplastic lesions was possible in most cases (n=25/31) on the basis of the CT-scans. Mean non-enhanced CT attenuation values of the neoplastic lesions ranged between 31 and 50 HU, of the inflammatory lesions between -251 and 9 HU. Both neoplastic and inflammatory lesions showed contrast enhancement (between 14 and 38 HU and between 2 and 95 HU respectively). The mediastinal abcesses enhanced mainly on the periphery of the lesion. A differentiation of the various types of neoplastic lesions based on the non-enhanced attenuation values was not successful. Only metastasis could be differentiated because of their distribution pattern.

Mechanisms of Ligand–Protein Interaction in Sec-14-like Transporters Investigated by Computer Simulations

We review our recent work on protein-ligand interactions in vitamin transporters of the Sec-14-like protein. Our studies focused on the cellular-retinaldehyde binding protein (CRALBP) and the alpha-tocopherol transfer protein (alpha-TTP). CRALBP is responsible for mobilisation and photo-protection of short-chain cis-retinoids in the dim-light visual cycle or rod photoreceptors. alpha-TTP is a key protein responsible for selection and retention of RRR-alpha-tocopherol, the most active isoform of vitamin E in superior animals. Our simulation studies evidence how subtle chemical variations in the substrate can lead to significant distortion in the structure of the complex, and how these changes can either lead to new protein function, or be used to model engineered protein variants with tailored properties. Finally, we show how integration of computational and experimental results can contribute in synergy to the understanding of fundamental processes at the biomolecular scale.

Precision of fit of implant-supported screw-retained 10-unit computer-aided-designed and computer-aided-manufactured frameworks made from zirconium dioxide and titanium: an in vitro study

OBJECTIVE To analyze the precision of fit of implant-supported screw-retained computer-aided-designed and computer-aided-manufactured (CAD/CAM) zirconium dioxide (ZrO) frameworks. MATERIALS AND METHODS Computer-aided-designed and computer-aided-manufactured ZrO frameworks (NobelProcera) for a screw-retained 10-unit implant-supported reconstruction on six implants (FDI positions 15, 13, 11, 21, 23, 25) were fabricated using a laser (ZrO-L, N = 6) and a mechanical scanner (ZrO-M, N = 5) for digitizing the implant platform and the cuspid-supporting framework resin pattern. Laser-scanned CAD/CAM titanium (TIT-L, N = 6) and cast CoCrW-alloy frameworks (Cast, N = 5) fabricated on the same model and designed similar to the ZrO frameworks were the control. The one-screw test (implant 25 screw-retained) was applied to assess the vertical microgap between implant and framework platform with a scanning electron microscope. The mean microgap was calculated from approximal and buccal values. Statistical comparison was performed with non-parametric tests. RESULTS No statistically significant pairwise difference was observed between the relative effects of vertical microgap between ZrO-L (median 14 μm; 95% CI 10-26 μm), ZrO-M (18 μm; 12-27 μm) and TIT-L (15 μm; 6-18 μm), whereas the values of Cast (236 μm; 181-301 μm) were significantly higher (P < 0.001) than the three CAD/CAM groups. A monotonous trend of increasing values from implant 23 to 15 was observed in all groups (ZrO-L, ZrO-M and Cast P < 0.001, TIT-L P = 0.044). CONCLUSIONS Optical and tactile scanners with CAD/CAM technology allow for the fabrication of highly accurate long-span screw-retained ZrO implant-reconstructions. Titanium frameworks showed the most consistent precision. Fit of the cast alloy frameworks was clinically inacceptable.

Are We Sims? How Computer Simulations Represent and What this Means for the Simulation Argument

N. Bostrom’s simulation argument and two additional assumptions imply that we are likely to live in a computer simulation. The argument is based upon the following assumption about the workings of realistic brain simulations: The hardware of a computer on which a brain simulation is run bears a close analogy to the brain itself. To inquire whether this is so, I analyze how computer simulations trace processes in their targets. I describe simulations as fictional, mathematical, pictorial, and material models. Even though the computer hardware does provide a material model of the target, this does not suffice to underwrite the simulation argument because the ways in which parts of the computer hardware interact during simulations do not resemble the ways in which neurons interact in the brain. Further, there are computer simulations of all kinds of systems, and it would be unreasonable to infer that some computers display consciousness just because they simulate brains rather than, say, galaxies.

Computer planned, image-guided combined resection and ablation for bilobar colorectal liver metastases

For patients with extensive bilobar colorectal liver metastases (CRLM), initial surgery may not be feasible and a multimodal approach including microwave ablation (MWA) provides the only chance for prolonged survival. Intraoperative navigation systems may improve the accuracy of ablation and surgical resection of so-called "vanishing lesions", ultimately improving patient outcome. Clinical application of intraoperative navigated liver surgery is illustrated in a patient undergoing combined resection/MWA for multiple, synchronous, bilobar CRLM. Regular follow-up with computed tomography (CT) allowed for temporal development of the ablation zones. Of the ten lesions detected in a preoperative CT scan, the largest lesion was resected and the others were ablated using an intraoperative navigation system. Twelve months post-surgery a new lesion (Seg IVa) was detected and treated by trans-arterial embolization. Nineteen months post-surgery new liver and lung metastases were detected and a palliative chemotherapy started. The patient passed away four years after initial diagnosis. For patients with extensive CRLM not treatable by standard surgery, navigated MWA/resection may provide excellent tumor control, improving longer-term survival. Intraoperative navigation systems provide precise, real-time information to the surgeon, aiding the decision-making process and substantially improving the accuracy of both ablation and resection. Regular follow-ups including 3D modeling allow for early discrimination between ablation zones and recurrent tumor lesions.

Dynamic computer simulation of electrophoretic enantiomer migration order and separation in presence of a neutral cyclodextrin

One-dimensional dynamic computer simulation was employed to investigate the separation and migration order change of ketoconazole enantiomers at low pH in presence of increasing amounts of (2-hydroxypropyl)-β-cyclodextrin (OHP-β-CD). The 1:1 interaction of ketoconazole with the neutral cyclodextrin was simulated under real experimental conditions and by varying input parameters for complex mobilities and complexation constants. Simulation results obtained with experimentally determined apparent ionic mobilities, complex mobilities, and complexation constants were found to compare well with the calculated separation selectivity and experimental data. Simulation data revealed that the migration order of the ketoconazole enantiomers at low (OHP-β-CD) concentrations (i.e. below migration order inversion) is essentially determined by the difference in complexation constants and at high (OHP-β-CD) concentrations (i.e. above migration order inversion) by the difference in complex mobilities. Furthermore, simulations with complex mobilities set to zero provided data that mimic migration order and separation with the chiral selector being immobilized. For the studied CEC configuration, no migration order inversion is predicted and separations are shown to be quicker and electrophoretic transport reduced in comparison to migration in free solution. The presented data illustrate that dynamic computer simulation is a valuable tool to study electrokinetic migration and separations of enantiomers in presence of a complexing agent.

Computer assisted planning and navigation of periacetabular osteotomy with range of motion optimization

Femoroacetabular impingement (FAI) before or after Periacetabular Osteotomy (PAO) is surprisingly frequent and surgeons need to be aware of the risk preoperatively and be able to avoid it intraoperatively. In this paper we present a novel computer assisted planning and navigation system for PAO with impingement analysis and range of motion (ROM) optimization. Our system starts with a fully automatic detection of the acetabular rim, which allows for quantifying the acetabular morphology with parameters such as acetabular version, inclination and femoral head coverage ratio for a computer assisted diagnosis and planning. The planned situation was optimized with impingement simulation by balancing acetabuar coverage with ROM. Intra-operatively navigation was conducted until the optimized planning situation was achieved. Our experimental results demonstrated: 1) The fully automated acetabular rim detection was validated with accuracy 1.1 ± 0.7mm; 2) The optimized PAO planning improved ROM significantly compared to that without ROM optimization; 3) By comparing the pre-operatively planned situation and the intra-operatively achieved situation, sub-degree accuracy was achieved for all directions.

A computer-assisted microscopic analysis of bone tissue developed inside a polyactive plymer implanted into an equine articular surface

One of the most promising applications for the restoration of small or moderately sized focal articular lesions is mosaicplasty (MP). Although recurrent hemarthrosis is a rare complication after MP, recently, various strategies have been designed to find an effective filling material to prevent postoperative bleeding from the donor site. The porous biodegradable polymer Polyactive (PA; a polyethylene glycol terephthalate - polybutylene terephthalate copolymer) represents a promising solution in this respect. A histological evaluation of the longterm PA-filled donor sites obtained from 10 experimental horses was performed. In this study, attention was primarily focused on the bone tissue developed in the plug. A computer-assisted image analysis and quantitative polarized light microscopic measurements of decalcified, longitudinally sectioned, dimethylmethylene blue (DMMB)- and picrosirius red (PS) stained sections revealed that the coverage area of the bone trabecules in the PA-filled donor tunnels was substantially (25%) enlarged compared to the neighboring cancellous bone. For this quantification, identical ROIs (regions of interest) were used and compared. The birefringence retardation values were also measured with a polarized light microscope using monochromatic light. Identical retardation values could be recorded from the bone trabeculae developed in the PA and in the neighboring bone, which indicates that the collagen orientation pattern does not differ significantly among these bone trabecules. Based on our new data, we speculate that PA promotes bone formation, and some of the currently identified degradation products of PA may enhance osteo-conduction and osteoinduction inside the donor canal.

Fully Automatic CT Segmentation for Computer-Assisted Pre-operative Planning of Hip Arthroscopy

Extraction of both pelvic and femoral surface models of a hip joint from CT data for computer-assisted pre-operative planning of hip arthroscopy is addressed. We present a method for a fully automatic image segmentation of a hip joint. Our method works by combining fast random forest (RF) regression based landmark detection, atlas-based segmentation, with articulated statistical shape model (aSSM) based hip joint reconstruction. The two fundamental contributions of our method are: (1) An improved fast Gaussian transform (IFGT) is used within the RF regression framework for a fast and accurate landmark detection, which then allows for a fully automatic initialization of the atlas-based segmentation; and (2) aSSM based fitting is used to preserve hip joint structure and to avoid penetration between the pelvic and femoral models. Validation on 30 hip CT images show that our method achieves high performance in segmenting pelvis, left proximal femur, and right proximal femur surfaces with an average accuracy of 0.59 mm, 0.62 mm, and 0.58 mm, respectively.

Computer Vision-Based Carbohydrate Estimation for Type 1 Diabetic Patients Using Smartphones

Background: Individuals with type 1 diabetes (T1D) have to count the carbohydrates (CHOs) of their meal to estimate the prandial insulin dose needed to compensate for the meal’s effect on blood glucose levels. CHO counting is very challenging but also crucial, since an error of 20 grams can substantially impair postprandial control. Method: The GoCARB system is a smartphone application designed to support T1D patients with CHO counting of nonpacked foods. In a typical scenario, the user places a reference card next to the dish and acquires 2 images with his/her smartphone. From these images, the plate is detected and the different food items on the plate are automatically segmented and recognized, while their 3D shape is reconstructed. Finally, the food volumes are calculated and the CHO content is estimated by combining the previous results and using the USDA nutritional database. Results: To evaluate the proposed system, a set of 24 multi-food dishes was used. For each dish, 3 pairs of images were taken and for each pair, the system was applied 4 times. The mean absolute percentage error in CHO estimation was 10 ± 12%, which led to a mean absolute error of 6 ± 8 CHO grams for normal-sized dishes. Conclusion: The laboratory experiments demonstrated the feasibility of the GoCARB prototype system since the error was below the initial goal of 20 grams. However, further improvements and evaluation are needed prior launching a system able to meet the inter- and intracultural eating habits.