Interactions of linear dicationic molecules with lipid A: structural requisites for optimal binding affinity

The structural determinants of the binding affinity of linear dicationic molecules toward lipid A have been examined with respect to the distance between the terminal cationic functions, the basicity, and the type of cationic moieties using a series of spermidine derivatives and pentamidine analogs by fluorescence spectroscopic methods, The presence of two terminal cationic groups corresponds to enhanced affinity, A distinct sigmoidal relationship between the intercationic distance and affinity was observed with a sharp increase at 11 Angstrom, levelling off at about 13 Angstrom. The basicity (pK) and nature of the cationic functions are poor correlates of binding potency, since molecules bearing primary amino, imidazolino, or guanido termini are equipotent, The interaction of pentamidine, a bisamidine drug, with lipid A, characterized in considerable detail employing the putative intermolecular excimerization of the drug, suggests a stoichiometry of 1:1 in the resultant complex, The binding is driven almost exclusively by electrostatic forces, and is dependent on the ionization states of both lipid A and the drug, Under conditions when lipid A is highly disaggregated, pentamidine binds specifically to bis-phosphoryl- but not to monophosphoryl-lipid A indicating that both phosphate groups of lipid A are necessary for electrostatic interactions by the terminal amidininium groups of the drug, Based on these data, a structural model is proposed for the pentamidine-lipid A complex, which may be of value in designing endotoxin antagonists from first principles.

BER-optimized linear parallel interference cancellers for multicarrier DS-CDMA systems

In this paper, we consider the design and bit-error performance analysis of linear parallel interference cancellers (LPIC) for multicarrier (MC) direct-sequence code division multiple access (DS-CDMA) systems. We propose an LPIC scheme where we estimate and cancel the multiple access interference (MAT) based on the soft decision outputs on individual subcarriers, and the interference cancelled outputs on different subcarriers are combined to form the final decision statistic. We scale the MAI estimate on individual subcarriers by a weight before cancellation. In order to choose these weights optimally, we derive exact closed-form expressions for the bit-error rate (BER) at the output of different stages of the LPIC, which we minimize to obtain the optimum weights for the different stages. In addition, using an alternate approach involving the characteristic function of the decision variable, we derive BER expressions for the weighted LPIC scheme, matched filter (MF) detector, decorrelating detector, and minimum mean square error (MMSE) detector for the considered multicarrier DS-CDMA system. We show that the proposed BER-optimized weighted LPIC scheme performs better than the MF detector and the conventional LPIC scheme (where the weights are taken to be unity), and close to the decorrelating and MMSE detectors.

Backbone chemical shift assignments of the acyl-acyl carrier protein intermediates of the fatty acid biosynthesis pathway of Plasmodium falciparum

We report the backbone chemical shift assignments of the acyl-acyl carrier protein (ACP) intermediates of the fatty acid biosynthesis pathway of Plasmodium falciparum. The acyl-ACP intermediates butyryl (C4), -octanoyl (C8), -decanoyl (C10), -dodecanoyl (C12) and -tetradecanoyl (C14)-ACPs display marked changes in backbone HN, Cα and Cβ chemical shifts as a result of acyl chain insertion into the hydrophobic core. Chemical shift changes cast light on the mechanism of expansion of the acyl carrier protein core.

Methodological perspectives for register-based health system performance assessment : Developing a hip fracture monitoring system in Finland

The resources of health systems are limited. There is a need for information concerning the performance of the health system for the purposes of decision-making. This study is about utilization of administrative registers in the context of health system performance evaluation. In order to address this issue, a multidisciplinary methodological framework for register-based data analysis is defined. Because the fixed structure of register-based data indirectly determines constraints on the theoretical constructs, it is essential to elaborate the whole analytic process with respect to the data. The fundamental methodological concepts and theories are synthesized into a data sensitive approach which helps to understand and overcome the problems that are likely to be encountered during a register-based data analyzing process. A pragmatically useful health system performance monitoring should produce valid information about the volume of the problems, about the use of services and about the effectiveness of provided services. A conceptual model for hip fracture performance assessment is constructed and the validity of Finnish registers as a data source for the purposes of performance assessment of hip fracture treatment is confirmed. Solutions to several pragmatic problems related to the development of a register-based hip fracture incidence surveillance system are proposed. The monitoring of effectiveness of treatment is shown to be possible in terms of care episodes. Finally, an example on the justification of a more detailed performance indicator to be used in the profiling of providers is given. In conclusion, it is possible to produce useful and valid information on health system performance by using Finnish register-based data. However, that seems to be far more complicated than is typically assumed. The perspectives given in this study introduce a necessary basis for further work and help in the routine implementation of a hip fracture monitoring system in Finland.

Sosiaalipalveluja kaikille ja kaiken ikää? : Tutkimus suomalaisten mielipiteistä ja kokemuksista sosiaalipalveluista sekä niiden suhteesta legitimiteettiin

This research analyses opinions on the system of social welfare services from the point of view of clients and the public in general in Finland. The approach is quantitative, drawing on theories of the welfare-state tradition. The data used comes from the comprehensive Welfare and Services in Finland survey compiled by STAKES. While previous research on the welfare state has predominantly focused on surveying public opinion on social protection, this research focuses on social welfare services. The main focus of this research is on publicly funded care provided by municipal social welfare services. In this research, social welfare services include child day care, services for people with disabilities, home-help services, counselling by social workers and social assistance. The research considered in particular whether the clients or the population has different opinions towards social welfare services or social benefits. In addition, the research partly covers areas of informal care provided by family and friends. The research material consisted of the STAKES Welfare and Services in Finland survey. The data was compiled in 2004 and 2006 by Statistics Finland. The research comprises five articles. Additional data have been extracted from social welfare statistics and registers. Multiple approaches were applied in the survey on welfare and services the methods in this research included interviews by phone and mail, and register data. The sample size was 5 810 people in 2004 and 5 798 in 2006. The response rates were 82.7% and 83.7%, respectively. The results indicate that a large majority (90%) of the Finnish population is of the opinion that the public sector should bear the main responsibility for organising social and health services. The system of social welfare services and its personnel have strong public support 73% and 80% respectively. However, new and even negative tones have emerged in the Finnish debate on social welfare services. Women are increasingly critical of the performance of social welfare services and the level of social protection. Furthermore, this study shows that women more often than men wish to see an increase in the amount of privately organised social welfare services. Another group critical of the performance of social welfare services are pensioners. People who had used social welfare services were more critical than those who had not used them. Thus, the severest criticism was received from the groups who use and gain most from public services and benefits. However, the education and income variables identified in earlier studies no longer formed a significant dividing line, although people with higher education tend to foster a more positive view of the performance of social welfare services as well as the level of social protection. Income differences did not bear any significance, that is, belonging to a high or low income group was not a determining factor in the attitude towards social welfare services or social benefits. According to the research, family and friends still form an informal yet significant support network in people's everyday lives, and its importance has not been diminished by services provided by the welfare state. The Finnish public considers child day care the most reliable form of social welfare services. Indeed, child day care has become the most universal sector of our system of social welfare services. Other services that instil confidence included counselling by social workers and services for people with disabilities. On the other hand, social assistance and home-help services received negative feedback. The negative views were based on a number of arguments. One argument contends that the home-help service system, which was originally intended for universal use, is crumbling. The preventive role of home-help services has been reduced. These results mirror the increasingly popular opinion that social welfare services are not produced for all those who need them, but to an increasing extent for a select few of them. Municipalities are struggling with their finances and this, combined with negative publicity, has damaged the public's trust in some municipal social welfare services. A welfare state never achieves a stable condition, but must develop over time, as the world around it changes. Following the 1990's recession, we are now in a position where we can start to develop a system that responds to the needs of the next generation. Study results indicating new areas of dissatisfaction reflect the need to develop and improve the services provided. It is also increasingly essential that social welfare services pay attention to the opinions of clients and the public. Should the gap between opinions and actual activities increase, the legitimacy of the whole system would be questioned. Currently, the vast majority of Finns consider the system of social welfare services adequate, which provides us with the continuity required to maintain and improve client-oriented and reasonably priced social welfare services. Paying attention to the signals given by clients and the general public, and reacting to them accordingly, will also secure the development and legitimacy of the system in the future.

Approximate methods for step function response of undamped non-linear spring mass systems with arbitrary hardening type spring characteristic

The possibility of applying two approximate methods for determining the salient features of response of undamped non-linear spring mass systems subjected to a step input, is examined. The results obtained on the basis of these approximate methods are compared with the exact results that are available for some particular types of spring characteristics. The extension of the approximate methods for non-linear systems with general polynomial restoring force characteristics is indicated.

Effect of static deflection on natural frequency of non-linear spring mass system by direct linearization method

An exact expression for the frequency of a non-linear cubic spring mass system is obtained considering the effect of static deflection. An alternative expression for the approximate frequency is also obtained by the direct linearization procedure; it is shown that this is very accurate as compared with the exact method. This approximate frequency equation is used to explain a “dual behaviour” of the frequency amplitude curves.

Response spectrum of non-linear spring mass system subjected to transient disturbances

The transient response spectrum of a cubic spring mass system subjected to a step function input is obtained. An approximate method is adopted where non-linear restoring force characteristic is replaced by two linear segments, so that the mean square error between them is a minimum. The effect of viscous damping on the peak response is also discussed for various values of the damping constant and the non-linearity restoring force parameter.

A Mechanistic Model for the Water-Gas Shift Reaction over Noble Metal Substituted Ceria

The water-gas shift (WGS) reaction was carried out in the presence of Pd and Pt substituted nanocrystalline ceria catalysts synthesized by solution combustion technique. The catalysts were characterized by powder XRD and XPS. The noble metals were found to be present in ionic form substituted for the cerium atoms. The catalysts showed highactivity for the WGS reaction with high conversions below 250 degrees C. The products of reaction were only carbon dioxide and hydrogen, and no hydrocarbons were observed even in trace quantities. The reactions were carried out with different amounts of noble metal ion substitution and 2% Pt substituted ceria was found to be the best catalyst. The various possible mechanisms for the reaction were proposed and tested for their consistency with experimental data. The dual site mechanism best described the kinetics of the reaction and the corresponding rate parameters were obtained.

Non-Linear vibration of an elastic string

Equations proposed in previous work on the non-linear motion of a string show a basic disagreement, which is here traced to an assumption about the longitudinal displacement u. It is shown that it is neither necessary nor justifiable to assume that u is zero; and also that the velocity of propagation of u disturbances in a string is different from that in an infinite medium, although this difference is usually negligible. After formulating the exact equations of motion for the string, a systematic procedure is described for obtaining approximations to these equations to any order, making only the assumption that the strain in the material of the string is small. The lowest order equations in this scheme are non-linear, and are used to describe the response of a string near resonance. Finally, it is shown that in the absence of damping, planar motion of a string is always unstable at sufficiently high amplitudes, the critical amplitude falling to zero at the natural frequency and its subharmonics. The effect of slight damping on this instability is also discussed.

A new approach to the study of non-linear non-autonomous systems

In this paper, a new approach to the study of non-linear, non-autonomous systems is presented. The method outlined is based on the idea of solving the governing differential equations of order n by a process of successive reduction of their order. This is achieved by the use of “differential transformation functions”. The value of the technique presented in the study of problems arising in the field of non-linear mechanics and the like, is illustrated by means of suitable examples drawn from different fields such as vibrations, rigid body dynamics, etc.

Study of a class of non-linear systems reducible to equivalent linear systems

In this paper, a method of arriving at transformations which convert a class of non-linear systems into equivalent linear systems, has been presented along with suitable examples, which illustrate its application.

Drag interaction effects in linear sphere-assemblies

Free-fall terminal velocities of single spheres and of single-row assemblies containing up to six spheres, with line of centres of spheres perpendicular to the direction of motion, have been determined in the particle Reynolds numbers range 0.2-4, and interaction effects obtained in the case of assemblies relative to drag on single isolated spheres, are discussed. The observed decrease in the drag on a sphere of an assembly is explained on the basis of theoretical considerations governing flow phenomena in such systems.