Fluorescent probe studies of biomembranes and model systems. The design and use of anionic site reporters

The fluorescence properties of a homologous series of fluorescent alkylamines are described. The binding of the probes to crythrocyte membranes increases with the length of the alkyl chain. The probes are shown to interact more strongly with membranes than with protein and lipid model systems. The binding of the probes to the membrane is sensitive to the cation concentration of the medium.

Random security scheme selection for mobile transactions

Security in a mobile communication environment is always a matter for concern, even after deploying many security techniques at device, network, and application levels. The end-to-end security for mobile applications can be made robust by developing dynamic schemes at application level which makes use of the existing security techniques varying in terms of space, time, and attacks complexities. In this paper we present a security techniques selection scheme for mobile transactions, called the Transactions-Based Security Scheme (TBSS). The TBSS uses intelligence to study, and analyzes the security implications of transactions under execution based on certain criterion such as user behaviors, transaction sensitivity levels, and credibility factors computed over the previous transactions by the users, network vulnerability, and device characteristics. The TBSS identifies a suitable level of security techniques from the repository, which consists of symmetric, and asymmetric types of security algorithms arranged in three complexity levels, covering various encryption/decryption techniques, digital signature schemes, andhashing techniques. From this identified level, one of the techniques is deployed randomly. The results shows that, there is a considerable reduction in security cost compared to static schemes, which employ pre-fixed security techniques to secure the transactions data.

A cooperative game theoretic approach to prototype selection

In this paper we consider the task of prototype selection whose primary goal is to reduce the storage and computational requirements of the Nearest Neighbor classifier while achieving better classification accuracies. We propose a solution to the prototype selection problem using techniques from cooperative game theory and show its efficacy experimentally.

Is there a role for microsampling in antibiotic pharmacokinetic studies?

- Introduction Clinical pharmacokinetic studies of antibiotics can establish evidence-based dosing regimens that improve the likelihood of eradicating the pathogen at the site of infection, reduce the potential for selection of resistant pathogens, and minimize harm to the patient. Innovations in small volume sampling (< 50 μL) or ‘microsampling’ may result in less-invasive sample collection, self-sampling and dried storage. Microsampling may open up opportunities in patient groups where sampling is challenging. - Areas Covered The challenges for implementation of microsampling to assure suitability of the results, include: acceptable study design, regulatory agency acceptance, and meeting bioanalytical validation requirements. This manuscript covers various microsampling methods, including dried blood/plasma spots, volumetric absorptive microsampling, capillary microsampling, plasma preparation technologies and solid-phase microextraction. - Expert Opinion The available analytical technology is being underutilized due to a lack of bridging studies and validated bioanalytical methods. These deficiencies represent major impediments to the application of microsampling to antibiotic pharmacokinetic studies. A conceptual framework for the assessment of the suitability of microsampling in clinical pharmacokinetic studies of antibiotics is provided. This model establishes a ‘contingency approach’ with consideration of the antibiotic and the type and location of the patient, as well as the more prescriptive bioanalytical validation protocols.

Impact of exercise selection on hamstring muscle activation

Objective: To determine the extent to which different strength training exercises selectively activate the commonly injured biceps femoris long head (BFLH) muscle. Methods: This two-part observational study recruited 24 recreationally active males. Part 1 explored the amplitudes and the ratios of lateral to medial hamstring (BF/MH) normalised electromyography (nEMG) during the concentric and eccentric phases of 10 common strength training exercises. Part 2 used functional magnetic resonance imaging (fMRI) to determine the spatial patterns of hamstring activation during two exercises which i) most selectively, and ii) least selectively activated the BF in part 1. Results: Eccentrically, the largest BF/MH nEMG ratio was observed in the 45° hip extension exercise and the lowest was observed in the Nordic hamstring (NHE) and bent-knee bridge exercises. Concentrically, the highest BF/MH nEMG ratio was observed during the lunge and 45° hip extension and the lowest was observed for the leg curl and bent-knee bridge. fMRI revealed a greater BFLH to semitendinosus activation ratio in the 45° hip extension than the NHE (p<0.001). The T2 increase after hip extension for BFLH, semitendinosus and semimembranosus muscles were greater than that for BFSH (p<0.001). During the NHE, the T2 increase was greater for the semitendinosus than for the other hamstrings (p≤0.002). Conclusion: This investigation highlights the non-uniformity of hamstring activation patterns in different tasks and suggests that hip extension exercise more selectively activates the BFLH while the NHE preferentially recruits the semitendinosus. These findings have implications for strength training interventions aimed at preventing hamstring injury.

Expression profiling of lymph nodes in tuberculosis patients reveal inflammatory milieu at site of infection

Extrapulmonary manifestations constitute 15 to 20% of tuberculosis cases, with lymph node tuberculosis (LNTB) as the most common form of infection. However, diagnosis and treatment advances are hindered by lack of understanding of LNTB biology. To identify host response, Mycobacterium tuberculosis infected lymph nodes from LNTB patients were studied by means of transcriptomics and quantitative proteomics analyses. The selected targets obtained by comparative analyses were validated by quantitative PCR and immunohistochemistry. This approach provided expression data for 8,728 transcripts and 102 proteins, differentially regulated in the infected human lymph node. Enhanced inflammation with upregulation of T-helper1-related genes, combined with marked dysregulation of matrix metalloproteinases, indicates tissue damage due to high immunoactivity at infected niche. This expression signature was accompanied by significant upregulation of an immunoregulatory gene, leukotriene A4 hydrolase, at both transcript and protein levels. Comparative transcriptional analyses revealed LNTB-specific perturbations. In contrast to pulmonary TB-associated increase in lipid metabolism, genes involved in fatty-acid metabolism were found to be downregulated in LNTB suggesting differential lipid metabolic signature. This study investigates the tissue molecular signature of LNTB patients for the first time and presents findings that indicate the possible mechanism of disease pathology through dysregulation of inflammatory and tissue-repair processes.

Role of 16S ribosomal RNA methylations in translation initiation in Escherichia coli

Translation initiation from the ribosomal P-site is the specialty of the initiator tRNAs (tRNA(fMet)). Presence of the three consecutive G-C base pairs (G29-C41, G30-C40 and G31-C39) in their anticodon stems, a highly conserved feature of the initiator tRNAs across the three kingdoms of life, has been implicated in their preferential binding to the P-site. How this feature is exploited by ribosomes has remained unclear. Using a genetic screen, we have isolated an Escherichia coli strain, carrying a G122D mutation in folD, which allows initiation with the tRNA(fMet) containing mutations in one, two or all the three G-C base pairs. The strain shows a severe deficiency of methionine and S-adenosylmethionine, and lacks nucleoside methylations in rRNA. Targeted mutations in the methyltransferase genes have revealed a connection between the rRNA modifications and the fundamental process of the initiator tRNA selection by the ribosome.

Role of histidine residues in EcoP15I DNA methyltransferase activity as probed by chemical modification and site-directed mutagenesis

Towards understanding the catalytic mechanism of M.EcoP15I [EcoP15I MTase (DNA methyltransferase); an adenine methyltransferase], we investigated the role of histidine residues in catalysis. M.EcoP15I, when incubated with DEPC (diethyl pyrocarbonate), a histidine-specific reagent, shows a time- and concentration-dependent inactivation of methylation of DNA containing its recognition sequence of 5'-CAGCAG-3'. The loss of enzyme activity was accompanied by an increase in absorbance at 240 nm. A difference spectrum of modified versus native enzyme shows the formation of N-carbethoxyhistidine that is diminished by hydroxylamine. This, along with other experiments, strongly suggests that the inactivation of the enzyme by DEPC was specific for histidine residues. Substrate protection experiments show that pre-incubating the methylase with DNA was able to protect the enzyme from DEPC inactivation. Site-directed mutagenesis experiments in which the 15 histidine residues in the enzyme were replaced individually with alanine corroborated the chemical modification studies and established the importance of His-335 in the methylase activity. No gross structural differences were detected between the native and H335A mutant MTases, as evident from CD spectra, native PAGE pattern or on gel filtration chromatography. Replacement of histidine with alanine residue at position 335 results in a mutant enzyme that is catalytically inactive and binds to DNA more tightly than the wild-type enzyme. Thus we have shown in the present study, through a combination of chemical modification and site-directed mutagenesis experiments, that His-335 plays an essential role in DNA methylation catalysed by M.EcoP15I.

Simultaneous material selection and geometry design of statically determinate trusses using continuous optimization

In this work, we explore simultaneous geometry design and material selection for statically determinate trusses by posing it as a continuous optimization problem. The underlying principles of our approach are structural optimization and Ashby’s procedure for material selection from a database. For simplicity and ease of initial implementation, only static loads are considered in this work with the intent of maximum stiffness, minimum weight/cost, and safety against failure. Safety of tensile and compression members in the truss is treated differently to prevent yield and buckling failures, respectively. Geometry variables such as lengths and orientations of members are taken to be the design variables in an assumed layout. Areas of cross-section of the members are determined to satisfy the failure constraints in each member. Along the lines of Ashby’s material indices, a new design index is derived for trusses. The design index helps in choosing the most suitable material for any geometry of the truss. Using the design index, both the design space and the material database are searched simultaneously using gradient-based optimization algorithms. The important feature of our approach is that the formulated optimization problem is continuous, although the material selection from a database is an inherently discrete problem. A few illustrative examples are included. It is observed that the method is capable of determining the optimal topology in addition to optimal geometry when the assumed layout contains more links than are necessary for optimality.

Structures and molecular-dynamics studies of three active-site mutants of bovine pancreatic phospholipase A(2)

Phospholipase A(2) hydrolyzes phospholipids at the sn-2 position to cleave the fatty-acid ester bond of L-glycerophospholipids. The catalytic dyad (Asp99 and His48) along with a nucleophilic water molecule is responsible for enzyme hydrolysis. Furthermore, the residue Asp49 in the calcium-binding loop is essential for controlling the binding of the calcium ion and the catalytic action of phospholipase A2. To elucidate the structural role of His48 and Asp49, the crystal structures of three active-site single mutants H48N, D49N and D49K have been determined at 1.9 angstrom resolution. Although the catalytically important calcium ion is present in the H48N mutant, the crystal structure shows that proton transfer is not possible from the catalytic water to the mutated residue. In the case of the Asp49 mutants, no calcium ion was found in the active site. However, the tertiary structures of the three active-site mutants are similar to that of the trigonal recombinant enzyme. Molecular-dynamics simulation studies provide a good explanation for the crystallographic results.

Splitting Algorithms for Fast Relay Selection: Generalizations, Analysis, and a Unified View

Relay selection for cooperative communications promises significant performance improvements, and is, therefore, attracting considerable attention. While several criteria have been proposed for selecting one or more relays, distributed mechanisms that perform the selection have received relatively less attention. In this paper, we develop a novel, yet simple, asymptotic analysis of a splitting-based multiple access selection algorithm to find the single best relay. The analysis leads to simpler and alternate expressions for the average number of slots required to find the best user. By introducing a new contention load' parameter, the analysis shows that the parameter settings used in the existing literature can be improved upon. New and simple bounds are also derived. Furthermore, we propose a new algorithm that addresses the general problem of selecting the best Q >= 1 relays, and analyze and optimize it. Even for a large number of relays, the scalable algorithm selects the best two relays within 4.406 slots and the best three within 6.491 slots, on average. We also propose a new and simple scheme for the practically relevant case of discrete metrics. Altogether, our results develop a unifying perspective about the general problem of distributed selection in cooperative systems and several other multi-node systems.

Selection of intrusion detection system threshold bounds for effective sensor fusion

The motivation behind the fusion of Intrusion Detection Systems was the realization that with the increasing traffic and increasing complexity of attacks, none of the present day stand-alone Intrusion Detection Systems can meet the high demand for a very high detection rate and an extremely low false positive rate. Multi-sensor fusion can be used to meet these requirements by a refinement of the combined response of different Intrusion Detection Systems. In this paper, we show the design technique of sensor fusion to best utilize the useful response from multiple sensors by an appropriate adjustment of the fusion threshold. The threshold is generally chosen according to the past experiences or by an expert system. In this paper, we show that the choice of the threshold bounds according to the Chebyshev inequality principle performs better. This approach also helps to solve the problem of scalability and has the advantage of failsafe capability. This paper theoretically models the fusion of Intrusion Detection Systems for the purpose of proving the improvement in performance, supplemented with the empirical evaluation. The combination of complementary sensors is shown to detect more attacks than the individual components. Since the individual sensors chosen detect sufficiently different attacks, their result can be merged for improved performance. The combination is done in different ways like (i) taking all the alarms from each system and avoiding duplications, (ii) taking alarms from each system by fixing threshold bounds, and (iii) rule-based fusion with a priori knowledge of the individual sensor performance. A number of evaluation metrics are used, and the results indicate that there is an overall enhancement in the performance of the combined detector using sensor fusion incorporating the threshold bounds and significantly better performance using simple rule-based fusion.

The selection, optimization, and compensation model in the work context: A systematic review and meta-analysis of two decades of research

Over the past two decades, the selection, optimization, and compensation (SOC) model has been applied in the work context to investigate antecedents and outcomes of employees' use of action regulation strategies. We systematically review, meta-analyze, and critically discuss the literature on SOC strategy use at work and outline directions for future research and practice. The systematic review illustrates the breadth of constructs that have been studied in relation to SOC strategy use, and that SOC strategy use can mediate and moderate relationships of person and contextual antecedents with work outcomes. Results of the meta-analysis show that SOC strategy use is positively related to age (rc = .04), job autonomy (rc = .17), self-reported job performance (rc = .23), non-self-reported job performance (rc = .21), job satisfaction (rc = .25), and job engagement (rc = .38), whereas SOC strategy use is not significantly related to job tenure, job demands, and job strain. Overall, our findings underline the importance of the SOC model for the work context, and they also suggest that its measurement and reporting standards need to be improved to become a reliable guide for future research and organizational practice.