From Isotropic to Anisotropic Side Chain Representations: Comparison of Three Models for Residue Contact Estimation

The criterion to determine residue contact is a fundamental problem in deriving knowledge-based mean-force potential energy calculations for protein structures. A frequently used criterion is to require the side chain center-to-center distance or the -to- atom distance to be within a pre-determined cutoff distance. However, the spatially anisotropic nature of the side chain determines that it is challenging to identify the contact pairs. This study compares three side chain contact models: the Atom Distance criteria (ADC) model, the Isotropic Sphere Side chain (ISS) model and the Anisotropic Ellipsoid Side chain (AES) model using 424 high resolution protein structures in the Protein Data Bank. The results indicate that the ADC model is the most accurate and ISS is the worst. The AES model eliminates about 95% of the incorrectly counted contact-pairs in the ISS model. Algorithm analysis shows that AES model is the most computational intensive while ADC model has moderate computational cost. We derived a dataset of the mis-estimated contact pairs by AES model. The most misjudged pairs are Arg-Glu, Arg-Asp and Arg-Tyr. Such a dataset can be useful for developing the improved AES model by incorporating the pair-specific information for the cutoff distance

Synergism between particle-based multiplexing and microfluidics technologies may bring diagnostics closer to the patient

In the field of medical diagnostics there is a growing need for inexpensive, accurate, and quick high-throughput assays. On the one hand, recent progress in microfluidics technologies is expected to strongly support the development of miniaturized analytical devices, which will speed up (bio)analytical assays. On the other hand, a higher throughput can be obtained by the simultaneous screening of one sample for multiple targets (multiplexing) by means of encoded particle-based assays. Multiplexing at the macro level is now common in research labs and is expected to become part of clinical diagnostics. This review aims to debate on the “added value” we can expect from (bio)analysis with particles in microfluidic devices. Technologies to (a) decode, (b) analyze, and (c) manipulate the particles are described. Special emphasis is placed on the challenges of integrating currently existing detection platforms for encoded microparticles into microdevices and on promising microtechnologies that could be used to down-scale the detection units in order to obtain compact miniaturized particle-based multiplexing platforms

Noncovalent cross-links in context with other structural and functional elements of proteins

Proteins are heteropolymers with evolutionary selected native sequences of residues. These native sequences code for unique and stable 3D structures indispensable for biochemical activity and for proteolysis resistance, the latter which guarantees an appropriate lifetime for the protein in the protease rich cellular environment. Cross-links between residues close in space but far in the primary structure are required to maintain the folded structure of proteins. Some of these cross-links are covalent, most frequently disulfide bonds, but the majority of the cross-links are sets of cooperative noncovalent long-range interactions. In this paper we focus on special clusters of noncovalent long-range interactions: the Stabilization Centers (SCs). The relation between the SCs and secondary structural elements as well as the relation between SCs and functionally important regions of proteins are presented to show a detailed picture of these clusters, which are believed to be primarily responsible for major aspects of protein stability

Екзогенні чинники ризику як умови для боротьби з туберкульозом

Objective – exogenous risk factors were studied at 142 new pulmonary ТВ cases with treatment default comparing with 105 succesfully treated patients under DOTS strategy. Materials and methods. The high ТВ incidence (104.6/100.000 in 2012) and low treatment succes rate (62 % in 2012) is mainly due to a high default (7.8 % in 2012) and failure rate (3.5 % in 2012) and characterise the epidemiological situation in Republic of Moldova. Results and discussion. According to predictible value, high risk factors for default were: male sex, economic disadvantaged state, single civic status, codependence, previously released from detention; medium risk factors - low education level, extrem poverty. Conclusions. Social, educational support and with drawl techics must be implemented to all patients exposed to risk factors for enhancing tuberculosis treatment result. Мета роботи – вивчення екзогенних чинників ризику в 142 нових випадках туберкульозу легень з неуспішним лікуванням порівняно з 105 успішно пролікованими хворими по DOTS-стратегії. Матеріали та методи. Захворюваність на туберкульоз в Республіці Молдова на сьогодні досить висока (104,6 на 100 тис. у 2012 p.), ефективність лікування низька (62 % у 2012 р.) в основному через переривання програми терапії (7,8 % у 2012 р.) і відмов (3,5 % у 2012 p.), що характеризує епідеміологічну ситуацію як не цілком благополучну. Результати та обговорення. До високих чинників ризику зараховують чоловічу стать, економічно несприятливу ситуацію в країні, високий рівень міграції, кількість звільнених з-під варти. До середніх чинників ризику зараховують неповну освіту і крайню бідність. Висновки. Соціальна освітня та технічна підтримка повинні бути реалізовані для всіх осіб, які належать до груп ризику із захворювання па туберкульоз, з метою підвищення ефективності контролю за епідеміологічною ситуацією з цього інфекційного захворювання

ß1/ß2/ß3-adrenoceptor knockout mice are obese and cold-sensitive but have normal lipolytic responses to fasting

Catecholamines are viewed as major stimulants of diet- and cold-induced thermogenesis and of fasting-induced lipolysis, through the &beta;-adrenoceptors (&beta;1/&beta;2/&beta;3). To test this hypothesis, we generated &beta;1/&beta;2/&beta;3-adrenoceptor triple knockout (TKO) mice and compared them to wild type animals. TKO mice exhibited normophagic obesity and cold-intolerance. Their brown fat had impaired morphology and lacked responses to cold of uncoupling protein-1 expression. In contrast, TKO mice had higher circulating levels of free fatty acids and glycerol at basal and fasted states, suggesting enhanced lipolysis. Hence, &beta;-adrenergic signalling is essential for the resistance to obesity and cold, but not for the lipolytic response to fasting.<br /

Optimization of the rotational moulding process for polyolefins

Hollow plastic parts can be made by a number of manufacturing methods, but only rotational moulding offers the ability to create one-piece, stress-free parts with attractive economics. However, the fundamental nature of rotational moulding is such that cycle times are long. Consequently, the plastic is subjected to relatively high temperatures, in the presence of air, for excessive periods of time. This can lead to thermal and oxidative degradation at the inner free surface of the plastic, resulting in a deterioration in the performance of the moulded part. The industry relies heavily on the experience of operators to establish the best processing conditions to avoid degradation, but this is problematic and inefficient. Unfortunately, automatic process control is difficult owing to the complex rotation of the mould. Recent developments highlighting the importance of the peak air temperature inside the mould have been an important step forward, but ever-increasing technical demands on moulders make it clear that more sophisticated process control is needed. It is known that the processing conditions that lead to degradation vary with factors that affect the heating rate, such as the type of mould used and the thickness of the end-product. In the work reported here, a method is proposed for predicting the onset of degradation, on the basis that this occurs when the concentration of antioxidant in the polymer reaches zero. Good agreement has been obtained between the experimental and predicted optimum processing temperature for polyethylenes stabilized with different antioxidant systems. A procedure is described for identifying the best rotational moulding conditions so that more efficient manufacturing methods can be achieved