Efficient computation of Morse-Smale complexes for three-dimensional scalar functions

The Morse-Smale complex is an efficient representation of the gradient behavior of a scalar function, and critical points paired by the complex identify topological features and their importance. We present an algorithm that constructs the Morse-Smale complex in a series of sweeps through the data, identifying various components of the complex in a consistent manner. All components of the complex, both geometric and topological, are computed, providing a complete decomposition of the domain. Efficiency is maintained by representing the geometry of the complex in terms of point sets.     

Identification of nasopharyngeal carcinoma antigens that induce humoral immune response by proteomic analysis

A proteomics-based approach has been used to identify proteins that commonly elicit a humoral immune response in nasopharyngeal carcinoma (NPC). Sera from 19 newly diagnosed NPC patients and 19 healthy individuals were analyzed for IgG autoantibodies against NPC proteins resolved by 2-DE. Protein spots that exhibited selective reactivity with sera from NPC patients were identified by MS. Among nine identified proteins, cytokeratin 19 (CK19), Erb3 binding protein (EBP1), and Rho GDP dissociation inhibitor-beta (Rho-GDI-2) induced autoantibodies in more than 36.8% of NPC patients but not in healthy individuals. Furthermore, Western blot analysis and immunohistochemical staining were performed to determine the expression and localization of CK19, EBP1, and Rho-GDI-2 in NPC and normal nasopharyngeal mucosal tissues. Up-regulated CK19 and EBP1, but not Rho-GDI-2, were observed in NPC vs. normal tissue. Subcellular localization of the three proteins in NPC tissue was same as that in the normal tissue. Thus, overexpression of CK19 and EBP1 may be one of the mechanisms for their autoantibody development in NPC. To validate the findings of a proteomic analysis, occurrence of autoantibodies against these three proteins was detected by immunoprecipitation and Western blot analysis in additional 30 NPC patients, 23 other types of cancer patients and 20 healthy individuals. Results showed that frequency of autoantibodies against CK19, EBP1 and Rho-GDI-2 in NPC patients was significantly higher than that in other types of cancer patients and healthy individuals. We conclude that CK19, EBP1 and Rho-GDI-2 may have utility in NPC screening and diagnosis.     

Contribution of laser microdissection-based technology to proteomic analysis in hepatocellular carcinoma developing on cirrhosis

Hepatocellular carcinoma (HCC) is a major cause of cancer worldwide. Proteomic studies provide opportunities to uncover targets for the diagnosis and treatment of this disease. However, in HCC developing in a setting of cirrhosis, the detection of proteome alterations may be hampered by the increased cellular heterogeneity of tissue when analysing global liver homogenates. The aim of this study was to evaluate whether the identification of proteome alterations in these HCC cases was improved when the differential protein profile between tumour and non-tumour areas of liver was determined using hepatocytes isolated by laser microdissection (LM). Differential profiles established with LM-hepatocytes and liver section homogenates using 2-DE and MS exhibited noticeable differences: 30% of the protein spots with deregulated expression in tumorous LM-samples did not display any modification in homogenates; conversely 15% of proteins altered in tumorous homogenates were not impaired in LM-hepatocytes. These alterations resulted from the presence in cirrhotic liver of fibrotic stroma which displayed a protein pattern different from that determined in LM-hepatocytes. In conclusion, our data demonstrate the interest of LM in distinguishing between fibrotic and hepatocyte proteome alterations and thus the benefit of LM to proteome studies of HCC developing in a context of cirrhosis.     

Detection of colorectal adenoma and cancer based on transthyretin and C3a-desArg serum levels

Colorectal cancer is the second leading cause of cancer death, and it develops from benign colorectal adenomas in over 95% of patients. Early detection of these cancer precursors by screening tests and their removal can potentially eradicate more than 95% of colorectal cancers before they develop. To discover sensitive and specific biomarkers for improvement of pre‐clinical diagnosis of colorectal adenoma and cancer, we analysed in two independent studies (n = 87 and n = 83 patients) serum samples from colorectal cancer (stage III), colorectal adenoma and control patients using SELDI‐TOF‐MS. Extensive statistical analysis was performed to establish homogeneous patient groups based on their clinical data. Two biomarkers that were each able to distinguish control patients from either colorectal adenoma or colorectal cancer patients (p<0.001) were identified as transthyretin (pre‐albumin) and C3a‐desArg by MS/MS and were further validated by antibody‐based assays (radial immunodiffusion, ELISA). A combination of both proteins clearly indicated the presence of colorectal adenoma or carcinoma. Using a cut‐off of <0.225 g/L for transthyretin and >1974 ng/mL for C3a‐desArg, we found a sensitivity and specificity for colorectal adenoma of 96% and 70%, respectively.     

Improving the contrast of topographical AFM images by a simple averaging filter

New image-processing methods were applied to atomic force microscopy images in order to visualize small details on the surface of virus particles and living cells. Polynomial line flattening and plane fitting of topographical images were performed as first step of the image processing. In a second step, a sliding window approach was used for low-pass filtering and data smoothing. The size of the filtering window was adjusted to the size of the small details of interest. Subtraction of the smoothed data from the original data resulted in images with enhanced contrast. Topographical features which are usually not visible can be easily discerned in the processed images. The method developed in this study rendered possible the detection of small patterns on viral particles as well as thin cytoskeleton fibers of living cells. It is shown that the sliding window approach gives better results than Fourier-filtering. Our method can be generally applied to increase the contrast of topographical images, especially when small features are to be highlighted on relatively high objects.     

Cancer incidence and causes of death among total hip replacement patients: a review based on Nordic cohorts with a special emphasis on metal-on-metal bearings

All patients with total hip arthroplasty (THA) are exposed to soluble or particulate forms of Co and Cr. Adverse effects of these wear products are not known. Data from Nordic registries is used to estimate adverse effects on a large scale, based mostly on metal-on-polyethylene bearings. Cancer incidence was in line with the general population when the patients were operated on for all indications and significantly decreased when the indication was primary osteoarthritis. Stomach cancer and colorectal cancers were significantly reduced and prostate cancer and skin melanoma significantly increased. There was no significant excess of cancer in target organs, i.e. liver, kidney, or haematopoietic cancers. THA patients had reduced mortality and extended life expectancy compared with standard Nordic populations. All-site cancer incidence of the first-generation metal-on-metal McKee-Farrar patients operated on for primary osteoarthritis was in line with the general population after follow-up for up to 28 years. General mortality of these patients was also reduced and they also had an extended life expectancy. Temporary increases in haematopoietic cancers at different follow-up periods were seen in some cohorts. This malignancy deserves a special record linkage monitoring while large numbers of young patients are provided with the second generation of metal-on-metal prostheses.     

The clinical repair of teeth using direct filling materials: engineering considerations

This paper reviews the way in which teeth damaged by caries may be repaired clinically. The mechanical effects of caries are described, as are the materials available to repair the damage caused by this disease. Studies are reported which have shown that caries reduces the compressive strength of the tooth to less than 50 per cent of its original value and that, by use of appropriate materials and placement techniques, this can be restored to some 80 per cent of this value. However, very few studies have been carried out which view tooth repair from an engineering perspective. Instead, emphasis is placed on determining clinical durability of repairs. This is related to repair strength but brings in other factors, such as the oral hygiene of the patient. Despite this complication, durability studies show that modern restorative materials perform well under clinical conditions, from which it may be concluded that the repair process allows a structure to be fabricated that is essentially sound from an engineering viewpoint, even if inferior to the original tooth structure provided by nature.     

ELNES at magic angle conditions

If one needs to cancel the effects of the anisotropy of the sample in a EELS experiment in the TEM, a particular couple of values for the collection and convergence angle must be used, called magic angle conditions (MAC). Recent developments in the theory have shown that a full relativistic treatment is mandatory to correctly describe this effect and that the MAC are strongly dependent on the acceleration voltage. We show how the analytical formula can be derived and give the exact analytical solution for the MAC which can then be easily applied to every practical case. We show the consequences of the energy dependence of the magic angle and that the parallelity of the beam will be the limiting factor for high acceleration voltages while for low acceleration voltages the contribution coming from Bragg spots may make it impossible to reach MAC.