Melting transitions in biomembranes

We investigated melting transitions in biological membranes in their native state that include their membrane proteins. These membranes originated from \textit{E. coli}, \textit{B. subtilis}, lung surfactant and nerve tissue from the spinal cord of several mammals. For some preparations, we studied the pressure, pH and ionic strength dependence of the transition. For porcine spine, we compared the transition of the native membrane to that of the extracted lipids. All preparations displayed melting transitions of 10-20 degrees below physiological or growth temperature, independent of the organism of origin and the respective cell type. The position of transitions in \textit{E. coli} membranes depends on the growth temperature. We discuss these findings in the context of the thermodynamic theory of membrane fluctuations that leads to largely altered elastic constants, an increase in fluctuation lifetime and in membrane permeability associated with the transitions. We also discuss how to distinguish lipid transitions from protein unfolding transitions. Since the feature of a transition slightly below physiological temperature is conserved even when growth conditions change, we conclude that the transitions are likely to be of major biological importance for the survival and the function of the cell.Comment: 12 pages, 6 Figures, 1 supplement with 1 figur

Large-scale Biometrics Deployment in Europe: Identifying Challenges and Threats

With large-scale biometrics deployment in the EU still in its infancy and with stakeholders racing to position themselves in view of the lucrative market that is forecasted, a study to identify challenges and threats that need to be dealt with was launched. This is the result: a report on Biometrics large-scale Deployment in Europe. The report tackles three main issues namely, the status, security / privacy and testing / certification processes. A survey was launched so as to help reveal the actual status of Biometrics large-scale Deployment initiatives in EU. The main outcome of the survey was that an open dissemination of implementation results policy is needed mainly on deployment plans, strategies, barriers and best practices. The security/ privacy challenges study identified a number of issues, the most important of which were related to proportionality and compliance to the existing regulatory framework while at the same time it revealed an important number of related actions aiming at ensuring both data security and privacy. The aim of the Bio Testing Europe study was double: to identify and collect comparable and certified results under different technologies, vendors and environments situations and to feed in this information to animate discussion among the members of a European network which would enhance the European testing and certification capacity. The study presents an integrated picture of the identified issues as well as a number of recommendations. With some of the systems that are being implemented involving millions of individuals as target users it is important for policy makers to adopt some of the options presented so as to address the identified through the study challengesJRC.J.4-Information Societ

Matematički pristup za unapređenje pouzdanosti podešavanja parametara u modeliranju procesa anaerobne digestije

The Nash-Sutcliffe model efficiency coefficient (ENSC) has been modified in order to assess the quality of simulations compared to observed data from the mesophilic monofermentation of grass silage. By applying the ENSC it is not only possible to find parameter sets with the best fit, but also to analyze the sensitivity of each parameter. For modeling the concentration of hydrogen, both the maximum uptake rate for hydrogen km_H2 and half-saturation coefficient of hydrogen KS_H2 are equally sensitive. Modeling the concentration of organic acids as acetate, propionate and butyrate, maximum uptake rate km as well as the free ammonia inhibition constant for acetate uptake KI_NH3 and hydrogen inhibition constants KI_H2, respectively are much more sensitive than their corresponding half-saturation constants KS. Only changes of hydrogen inhibition constants and maximum uptake of acetate compared to the ADM1 suggested values (for mesophilic sludge digestion) were necessary to fit the measurements.Model Nash-Sutcliffe koeficijenta efikasnosti (ENSC) primijenjen je u svrhu procjene kvalitete simulacija u usporedbi s promatranim podacima mezofilne monofermentacije travne silaže. Primjenom ENSC nije moguće pronaći najbolje moguće odgovarajuće skupove parametara, isto tako nije moguće analizirati osjetljivost svakog parametra. Za modeliranje koncentracije vodika, jednako su osjetljivi maksimalna stopa unosa vodika km_H2 kao i poluzasićenost vodikom KS_H2. Modeliranje koncentracije organskih kiselina kao acetata, propionata i butirata, maksimalni unos km jednako kao i konstanta inhibicije bez amonijaka za unos acetata KI_NH3 i konstanta inhibicije vodika KI_H2, mnogo više su osjetljiviji u odnosu na njihove odgovarajuće poluzasićene konstante KS. Za odgovarajuća mjerenja samo su bile potrebne promjene konstante inhibicije vodika i maksimalnog unosa acetate u usporedbi s ADMI predloženim vrijednostima (za mezofilnu digestiju taloga)

Almost-equidistant sets

For a positive integer d, a set of points in d-dimensional Euclidean space is called almost-equidistant if for any three points from the set, some two are at unit distance. Let f(d) denote the largest size of an almost-equidistant set in d-space. It is known that f(2) = 7 , f(3) = 10 , and that the extremal almost-equidistant sets are unique. We give independent, computer-assisted proofs of these statements. It is also known that f(5) ≥ 16. We further show that 12 ≤ f(4) ≤ 13 , f(5) ≤ 20 , 18 ≤ f(6) ≤ 26 , 20 ≤ f(7) ≤ 34 , and f(9) ≥ f(8) ≥ 24. Up to dimension 7, our work is based on various computer searches, and in dimensions 6–9, we give constructions based on the known construction for d= 5. For every dimension d≥ 3 , we give an example of an almost-equidistant set of 2 d+ 4 points in the d-space and we prove the asymptotic upper bound f(d) ≤ O(d 3 / 2)

Structural basis for activation of the therapeutic l-nucleoside analogs 3TC and troxacitabine by human deoxycytidine kinase

l-nucleoside analogs represent an important class of small molecules for treating both viral infections and cancers. These pro-drugs achieve pharmacological activity only after enzyme-catalyzed conversion to their tri-phosphorylated forms. Herein, we report the crystal structures of human deoxycytidine kinase (dCK) in complex with the l-nucleosides (−)-β-2′,3′-dideoxy-3′-thiacytidine (3TC)—an approved anti-human immunodeficiency virus (HIV) agent—and troxacitabine (TRO)—an experimental anti-neoplastic agent. The first step in activating these agents is catalyzed by dCK. Our studies reveal how dCK, which normally catalyzes phosphorylation of the natural d-nucleosides, can efficiently phosphorylate substrates with non-physiologic chirality. The capability of dCK to phosphorylate both d- and l-nucleosides and nucleoside analogs derives from structural properties of both the enzyme and the substrates themselves. First, the nucleoside-binding site tolerates substrates with different chiral configurations by maintaining virtually all of the protein-ligand interactions responsible for productive substrate positioning. Second, the pseudo-symmetry of nucleosides and nucleoside analogs in combination with their conformational flexibility allows the l- and d-enantiomeric forms to adopt similar shapes when bound to the enzyme. This is the first analysis of the structural basis for activation of l-nucleoside analogs, providing further impetus for discovery and clinical development of new agents in this molecular class

Highly Specific Antibodies for Co-Detection of Human Choline Kinase α1 and α2 Isoforms

BACKGROUND: Choline kinase is the first enzyme in the CDP-choline pathway that synthesizes phosphatidylcholine, the major phospholipid in eukaryotic cell membranes. In humans, choline kinase exists as three isoforms (CKα1, α2, and β). Specific inhibition of CKα has been reported to selectively kill tumoral cells. Monoclonal and polyclonal antibodies against CKα used in previous studies to detect the level of this isozyme in different cellular or biochemical contexts were able to detect either the α1 or the α2 isoform. METHODOLOGY/PRINCIPAL FINDINGS: In this study, an antiserum against CKα was produced by immunizing rabbits with denatured, purified recombinant CKα2 full-length protein. This antiserum was highly specific for CKα when tested with extracts from different cell lines, and there was no cross reactivity with purified CKβ and other related proteins like human ethanolamine kinases (EK) and yeast choline or ethanolamine kinases. The antiserum simultaneously detected both CKα1 and α2 isoforms in MCF-7 and HepG2 cell extracts, but not in HeLa, HCT-116, and mouse embryonic stem cell extracts. Subsequent protein dot blot assay of total CKα in a human normal/tumor protein array of 30 tissue samples by using the antiserum showed that CKα was not overexpressed in all tumor tissues when compared to their normal counterparts. Most striking differences between tumor and normal CKα expression levels were observed in kidney (11-fold higher in tumor) and liver (15-fold lower in tumor) samples. CONCLUSION/SIGNIFICANCE: Apart from its high sensitivity and specificity, the antiserum produced in this work, which does not require further purification, has the advantage of co-detecting both α1 and α2 isoforms in cell extracts for direct comparison of their expression levels

3rd Probabilistic Workshop Technical Systems, Natural Hazards

Modern engineering structures should ensure an economic design, construction and operation of structures in compliance with the required safety for persons and the environment. In order to achieve this aim, all contingencies and associated consequences that may possibly occur throughout the life cycle of the considered structure have to be taken into account. Today, the development is often based on decision theory, methods of structural reliability and the modeling of consequences. Failure consequences are one of the significant issues that determine optimal structural reliability. In particular, consequences associated with the failure of structures are of interest, as they may lead to significant indirect consequences, also called follow-up consequences. However, apart from determining safety levels based on failure consequences, it is also crucially important to have effective models for stress forces and maintenance planning ... (aus dem Vorwort

Materials perspective of polymers for additive manufacturing with selective laser sintering

The fundamental factors of polymer powders, their importance for successful selective laser sintering (SLS) processing, and the outstanding position of polyamide 12 (PA12) powders in this connection are presented. Considering key factors, the combination of intrinsic and extrinsic properties necessary to generate a powder likely for SLS application is emphasized. Only a specific combination of indicated points leads to success. This is one reason for fewer materials commercially available to date for SLS application. PA12 and some dry blends based on PA12 are today the materials that are used to generate almost all commercial SLS parts. The specific performance of particular PA12 for SLS processing is unmatched from other polymers so far. Reasons are the precise molecular control of SLS polymers for thermal behavior (enlargement of sintering window) and the open chain structure. This is for generation of sufficient mechanical properties and to induce interlayer bonding of successively sintered layers to reduce anisotropic part