Is it mathematically correct to fit AFM data (obtained on biological materials) to equations arising from Hertzian mechanics?

When testing soft biological samples using the Atomic Force Microscopy (AFM) nanoindentation method, the force-indentation data is usually fitted to the equations provided by Hertzian mechanics. Nevertheless, a significant question remains up to date; is this a correct approach from a mathematical perspective? Biological materials are heterogeneous, so 'what do we calculate' when using a classic fitting approach? In this paper, conclusive answers to the abovementioned questions are provided. In addition, a new tool for the nanomechanical characterization of biological samples, the depth-dependent mechanical properties maps, is introduced.

SPNsim: A database of simulated solitary pulmonary nodule PET/CT images facilitating computer aided diagnosis.

The aim of the present work was to design and develop a database of simulated solitary pulmonary nodules (SPN) in pairs of computed tomography (CT) and positron emission tomography (PET) images, using Monte Carlo (MC) simulation methods. We have developed an SPN image modeling pipeline to feed the database entitled SPNsim. The database is web-accessible and it is contains two subsets of simulated PET/CT SPN images. The first subset is currently composed of 1000 cases containing pairs of the transaxial CT and the corresponding PET slice with various types of simulated SPNs, presented as individual records. The second subset contains pairs of the transaxial CT and the corresponding PET slice of simulated SPNs, presenting cases of graded difficulty in diagnosis. The users of the database will have the ability to set queries in order to retrieve cases with certain characteristics, as well as characterized image sets. All images are freely available and may be downloaded from the website. SPNsim provides a useful reference data set for training and evaluation of computer aided detection (CAD) and diagnosis (CADx) systems focusing on SPN.

Molecular indicators for pollution source identification in marine and terrestrial water of the industrial area of Kavala city, North Greece.

Eight terrestrial and four marine water samples were collected from the industrial section of the city of Kavala in northern Greece to determine the occurrence and distribution of organic contaminants, as well as to identify the molecular markers of different emission sources. The samples were analyzed by means of non-target screening analyses. The analytical procedure included a sequential extraction of the samples, GC-FID, GC/MS analyses, and additional quantitative analyses of selected pollutants. The results show a wide variety of compounds including halogenated compounds, technical additives and metabolites, phosphates, phthalates, benzothiazoles, etc. A close relationship between many of the contaminants and their emission sources was determined based on their molecular structures and information on technical applications.

Optimization of nitrogen removal and start-up of Psyttalia sewage treatment works.

Bench scale experiments were conducted in order to finalize the design of the secondary treatment stage of Psyttalia Sewage Treatment Works that serves the Greater Athens area with a population equivalent of 3.5 million. Carbon and nitrogen removal efficiencies and activated sludge settling characteristics were determined through continuous flow experiments and determination of the maximum specific utilization rates of ammonia (AUR) and nitrate (NUR). According to the results of the pilot experiments the need arose for a significant increase in the initial design's anoxic volume to ensure a 70% average annual nitrogen removal. AUR experiments showed an insignificant inhibition to the nitrification process in the order of 0-30%, representative of typical domestic sewage. The findings of the pilot study were in good agreement with full scale data obtained during the start up of Psyttalia biological treatment plant. According to full scale data and AUR tests a very satisfactory nitrogen removal efficiency was obtained during start up. Finally both lab scale and full scale data indicated that the activated sludge plant operating on Psyttalia primary effluent that has a high oil and grease content, is prompt to experience foaming problems due to the excessive growth of filamentous microorganisms M. parvicella and Gordona amarae - like microorganisms.

Is there a role of whole body bone scan in early stages of non small cell lung cancer patients.

PURPOSE: The aim of our study was to re-evaluate the role of whole-body bone scanning (WBBS) in detecting bone metastases in apparently operable stages of non small cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: We made a retrospective analysis of 60 patients (53 males, 7 females, aged 47-87 years, mean 68+/-4) between 2004-2006. All patients had a full series of imaging staging procedures including WBBS. Their medical records were reviewed with respect to how often bone metastases were detected and whether or not the patients showed any symptoms or laboratory abnormalities indicating bone involvement. RESULTS: Skeletal metastases (confirmed afterwards by x-ray, computed tomography or biopsy) were found in 11 (18.3%) patients. All of them had normal serum alkaline phosphatase and calcium concentrations. Eleven patients had symptoms suggesting bone metastases and 49 were asymptomatic. Bone metastases were detected in 3 (27.2%) of 11 clinically symptom-positive patients and in 8 (16.3%) of 49 clinically symptom-negative patients. CONCLUSION: The present study indicates that if bones scans were done only in patients reporting skeletal symptoms an important number of patients (16.3%) would have been misstaged due to asymptomatic bone metastases. We conclude that in patients with apparently operable NSCLC preoperative staging using WBBS is useful to avoid under-staging and futile surgery.

Investigation of the uptake ability of fly ashes produced after lignite combustion.

Fly ash samples from the five steam electric power stations of the Lignite Center of Western Macedonia were used in this study. They consisted mainly of anhydrite, lime, quartz and amorphous material as well as feldspars, calcite, micas + clays, portlandite and gehlenite which were all present in minor amounts. Anhydrite, lime and portlandite in the fly ash samples diminished upon treatment with ammonium acetate aqueous solution, whereas quartz, feldspars, gehlenite and amorphous material were enriched. The uptake ability of the fly ash samples ranged from 89 to 101 mequ./100g. The uptake ability of the samples was mainly attributed to the amorphous material and the microporous minerals, micas + clays. The amorphous material content was estimated at between 17 and 20 wt% in the treated fly ashes and may be unburned organic matter and amorphous inorganic material that resulted during the combustion of the lignite. A positive correlation was observed between the uptake ability and the total percentage of amorphous material and micas + clays. The relatively high uptake ability of the fly ash samples could lead to additional industrial and environmental uses of the fly ashes. The environmental advantage of fly ash exploitation will be particularly important for large electric power centers, such as the LCWM.

Presenilin-1 binds cytoplasmic epithelial cadherin, inhibits cadherin/p120 association, and regulates stability and function of the cadherin/catenin adhesion complex.

Here we show that presenilin-1 (PS1), a protein involved in Alzheimer's disease, binds directly to epithelial cadherin (E-cadherin). This binding is mediated by the large cytoplasmic loop of PS1 and requires the membrane-proximal cytoplasmic sequence 604-615 of mature E-cadherin. This sequence is also required for E-cadherin binding of protein p120, a known regulator of cadherin-mediated cell adhesion. Using wild-type and PS1 knockout cells, we found that increasing PS1 levels suppresses p120/E-cadherin binding, and increasing p120 levels suppresses PS1/E-cadherin binding. Thus PS1 and p120 bind to and mutually compete for cellular E-cadherin. Furthermore, PS1 stimulates E-cadherin binding to beta- and gamma-catenin, promotes cytoskeletal association of the cadherin/catenin complexes, and increases Ca(2+)-dependent cell-cell aggregation. Remarkably, PS1 familial Alzheimer disease mutant DeltaE9 increased neither the levels of cadherin/catenin complexes nor cell aggregation, suggesting that this familial Alzheimer disease mutation interferes with cadherin-based cell-cell adhesion. These data identify PS1 as an E-cadherin-binding protein and a regulator of E-cadherin function in vivo.

Presenilin-1 forms complexes with the cadherin/catenin cell-cell adhesion system and is recruited to intercellular and synaptic contacts.

In MDCK cells, presenilin-1 (PS1) accumulates at intercellular contacts where it colocalizes with components of the cadherin-based adherens junctions. PS1 fragments form complexes with E-cadherin, beta-catenin, and alpha-catenin, all components of adherens junctions. In confluent MDCK cells, PS1 forms complexes with cell surface E-cadherin; disruption of Ca(2+)-dependent cell-cell contacts reduces surface PS1 and the levels of PS1-E-cadherin complexes. PS1 overexpression in human kidney cells enhances cell-cell adhesion. Together, these data show that PS1 incorporates into the cadherin/catenin adhesion system and regulates cell-cell adhesion. PS1 concentrates at intercellular contacts in epithelial tissue; in brain, it forms complexes with both E- and N-cadherin and concentrates at synaptic adhesions. That PS1 is a constituent of the cadherin/catenin complex makes that complex a potential target for PS1 FAD mutations.

Enrichment of presenilin 1 peptides in neuronal large dense-core and somatodendritic clathrin-coated vesicles.

Presenilin 1 is an integral membrane protein specifically cleaved to yield an N-terminal and a C-terminal fragment, both membrane-associated. More than 40 presenilin 1 mutations have been linked to early-onset familial Alzheimer disease, although the mechanism by which these mutations induce the Alzheimer disease neuropathology is not clear. Presenilin 1 is expressed predominantly in neurons, suggesting that the familial Alzheimer disease mutants may compromise or change the neuronal function (s) of the wild-type protein. To elucidate the function of this protein, we studied its expression in neuronal vesicular systems using as models the chromaffin granules of the neuroendocrine chromaffin cells and the major categories of brain neuronal vesicles, including the small clear-core synaptic vesicles, the large dense-core vesicles, and the somatodendritic and nerve terminal clathrin-coated vesicles. Both the N- and C-terminal presenilin 1 proteolytic fragments were greatly enriched in chromaffin granule and neuronal large dense-core vesicle membranes, indicating that these fragments are targeted to these vesicles and may regulate the large dense-core vesicle-mediated secretion of neuropeptides and neurotransmitters at synaptic sites. The presenilin 1 fragments were also enriched in the somatodendritic clathrin-coated vesicle membranes, suggesting that they are targeted to the somatodendritic membrane, where they may regulate constitutive secretion and endocytosis. In contrast, these fragments were not enriched in the small clear-core synaptic vesicle or in the nerve terminal clathrin-coated vesicle membranes. Taken together, our data indicate that presenilin 1 proteolytic fragments are targeted to specific populations of neuronal vesicles where they may regulate vesicular function. Although full-length presenilin 1 was present in crude homogenates, it was not detected in any of the vesicles studied, indicating that, unlike the presenilin fragments, full-length protein may not have a vesicular function.

Insulin potentiates the transactivation potency of the glucocorticoid receptor.

A single copy of a glucocorticoid-responsive element (GRE) is sufficient in mediating the combinatorial response of a promoter to both glucocorticoids and insulin in HepG2 cells. This requires the presence of active glucocorticoid receptor (GR) since the response is significantly inhibited by the anti-glucocorticoid RU30406. The N'- and C'-terminal parts of the GR protein are not involved in mediating the response. Insulin had no effect on GR binding to GRE but it affected both the level and the phosphorylation state of nuclear-bound GR. Thus, insulin alters the GR transactivation potency while, concomitantly, modifies the molecule at the posttranslational level.

Insulin enhances glucocorticoid induction of gene expression in a sequence specific manner.

Glucocorticoid receptor (GR) induces transcriptional activation of specific genes by binding to cis-acting enhancer sequences termed glucocorticoid responsive elements (GREs). Insulin regulates gene transcription part of which is mediated sequences dominated by GREs. By transient expression in HTC cells of fusion gene consist MMTV 5' flanking sequences containing the GREs on the thymidine kinase promoter (TK) and the coding region of the chloramphenicol acetyl transferase gene (CAT), we demonstrate that insulin increases 2-fold the produced induction from dexamethasone, while insulin alone does not exceed any significant effect. This synergistic effect of insulin is sequence specific since, expression of the glucocorticoid unresponsive gene RSV-CAT at the same cell line is affected neither by insulin nor dexamethasone or both. Transient expression of CAT constructs with progressive 5' deletion mutants of mouse mammary tumor virus (MMTV) promoter, fail to detect a cis-acting insulin responsive DNA element, that participates in increased dexamethasone mediated induction. We believe that insulin activates an intracellular mediator-transcription factor, that stimulates gene expression indirectly, by interaction with the glucocorticoid receptor.

[Is the postoperative course following goniotrepanation modified by the age of the patient?]. / Wird der postoperative Verlauf nach Goniotrepanation vom Alter des Patienten beeinflusst?

The authors tried to establish whether the patient's age has any bearing on the postoperative course of goniotrepanation. A total of 150 eyes operated on, which had been regularly followed up for more than 10 years, were classified in three age groups, each comprising 50 eyes. The following parameters were evaluated: indication for the operation, behavior of the postoperative I.O.P., behaviour of the filtering bleb, behavior of the visual functions, and late complications. The comparative investigations produced the following findings: (1) The postoperative mean IOP value is independent of the patient's age; (2) visual functions were adversely affected to a significant degree postoperatively in older patients, and (3) a cystic configuration of the filtering bleb was significantly more common in older individuals. On the basis of these findings the authors recommend covered sclerectomy procedures, even in younger individuals suffering from chronic simple glaucoma, because the prognosis for the functions and the ultimate fate of the eye is reasonably good.

[Are functional disturbances in chronic simple glaucoma indispensable for carrying out a covered sclerectomy operation? (author's transl)]. / Ist die Funktionsstörung bei Glaucoma simplex eine unerlässliche Voraussetzung für eine gedeckte Sklerektomie?

The existence of functional disturbances in chronic simple glaucoma is generally considered to be an indispensable prerequisite in deciding to perform a glaucoma operation. The favorable results obtained with the covered sclerectomies and their small percentage of postoperative complications have encouraged the authors to prefer operative treatment over conservative magangement more often in chronic simple glaucoma. The decision between operative and conservative management does not however depend solely on the existence of visual field defects. It also depends on the social status of the patient, poor drug tolerance and other factors as well.