Mass Transport Perspective on an Accelerated Exclusion Process: Analysis of Augmented Current and Unit-Velocity Phases

In an accelerated exclusion process (AEP), each particle can "hop" to its adjacent site if empty as well as "kick" the frontmost particle when joining a cluster of size ℓ⩽ℓ_{max}. With various choices of the interaction range, ℓ_{max}, we find that the steady state of AEP can be found in a homogeneous phase with augmented currents (AC) or a segregated phase with holes moving at unit velocity (UV). Here we present a detailed study on the emergence of the novel phases, from two perspectives: the AEP and a mass transport process (MTP). In the latter picture, the system in the UV phase is composed of a condensate in coexistence with a fluid, while the transition from AC to UV can be regarded as condensation. Using Monte Carlo simulations, exact results for special cases, and analytic methods in a mean field approach (within the MTP), we focus on steady state currents and cluster sizes. Excellent agreement between data and theory is found, providing an insightful picture for understanding this model system.

Investigation of Human-Structure Interaction Through Experimental and Analytical Studies

Vibration serviceability is a widely recognized design criterion for assembly-type structures, such as stadiums, that are likely subjected to rhythmic human-induced excitation. Human-induced excitation of a structure occurs from the movement of the occupants such as walking, running, jumping, or dancing. Vibration serviceability is based on the level of comfort that people have with the vibrations of a structure. Current design guidance uses the natural frequency of the structure to assess vibration serviceability. However, a phenomenon known as human-structure interaction suggests that there is a dynamic interaction between the structure and passive occupants, altering the natural frequency of the system. Human-structure interaction is dependent on many factors, including the dynamic properties of the structure, posture of the occupants, and relative size of the crowd. It is unknown if the shift in natural frequency due to humanstructure interaction is significant enough to warrant consideration in the design process. This study explores the interface of both structural and crowd characteristics through experimental testing to determine if human-structure interaction should be considered because of its potential impact on serviceability assessment. An experimental test structure that represents the dynamic properties of a cantilevered stadium structure was designed and constructed. Experimental modal analysis was implemented to determine the dynamic properties of the empty test structure and when occupied with up to seven people arranged in different locations and postures. Comparisons of the dynamic properties were made between the empty and occupied testing configurations and analytical results from the use of a dynamic crowd model recommended from the Joint Working Group of Europe. Data trends lead to the development of a refined dynamic crowd model. This dynamic model can be used in conjunction with a finite element model of the test structure to estimate the dynamic influence due to human-structure interaction due to occupants standing with straight knees. In the future, the crowd model will be refined and can aid in assessing the dynamic properties of in-service stadium structures.

Experimental Evaluation of the Influence of Human-Structure Interaction for Vibration Serviceability

The effects of human-structure interaction on the dynamic performance of occupied structures have long been observed. The inclusion of the effects of human-structure interaction is important to ensure that the dynamic response of a structure is not overestimated. Previous observations, both in service and in the laboratory, have yielded results indicating that the effects are dependent on the natural frequency of the structure, the posture of the occupants, and the mass ratio of the occupants to the structure. These results are noteworthy, but are limited in their application,because the data are sparse and are only pertinent to a specific set of characteristics identified in a given study. To examine these characteristics simultaneously and consistently, an experimental test structure was designed with variable properties to replicate a variety of configurations within a controlled setting focusing on the effects of passive occupants. Experimental modal analysis techniques were employed to both the empty and occupied conditions of the structure and the dynamic properties associated with each condition were compared. Results similar to previous investigations were observed, including both an increase and a decrease in natural frequency of the occupied structure with respect to the empty structure, as well as the identification of a second mode of vibration. The damping of the combined system was higher for all configurations. Overall, this study provides a broad data set representing a wide array of configurations. The experimental results of this study were used to assess current recommendations for the dynamic properties of a crowd to analytically predict the effects of human-structure interaction. The experimental results were used to select a set of properties for passive, standing occupants and develop a new model that can more accurately represent the behavior of the human-structure system as experimentally measured in this study.

Interethnic Interaction Dynamics in the Russian Federation

The collapse of the Soviet Union at the beginning of the 1990s also meant the end of the idea of a common soviet identity incarnated in the "soviet man" and the new "historic community of the soviet people". While this idea still lives on in the generations of the 1920s to 1940s, the younger generations tend to prefer identification with family, profession, ethnic group or religion. Ms. Alexakhina set out to investigate different interethnic interaction strategies in the multi-ethnic context of the Russian Federation, with an emphasis on analysing the role of cultural and ethno-demographic characteristics of minority ethnic groups. It aimed to identify those specific patterns of interaction dynamics that have emerged in response to the political and economic transformation at present under way. The basic supposition was that the size and growth of an ethnic population are defined not only by demographic features such as fertility, mortality and net migration, but are also dependent on processes interethnic interaction and ethnic transition. The central hypothesis of the project was that the multi-ethnic and multi-cultural composition of Russia is apparently manifesting itself in the ethnic minority groups in various forms, but particularly in the form of ethnic revival and/or assimilation. The results of these complex phenomena are manifested as changes in ethnic attachments (national re-identification and language behaviour (multi-lingualism, language transition and loss of the mother tongue). The stress of the political and economic crisis has stimulated significant changes in ethnographic, social and cultural characteristics of inter-ethnic dynamics such as the rate of national re-identification, language behaviour, migration activity and the spread of mixed marriages, among both those minorities with a long history of settlement in Russia and those that were annexed during the soviet period. Patterns of language behaviour and the spread of mixed marriages were taken as the main indicators of the directions of interethnic interaction described as assimilation, ethnic revival and cultural pluralism. The first stage of the research involved a statistical analysis of census data from 1959 to 1994 in order to analyse the changing demographic composition of the largest ethnic groups of the Russian Federation. Until 1989 interethnic interaction in soviet society was distinguished by the process of russification but the political and economic transformation has stimulated the process of ethnic revival, leading to an apparent fall in the size of the Russian population due to ethnic re-identification by members of other ethnic groups who had previously identified themselves as Russian. Cross-classification of nationalities by demographic, social and cultural indicators has shown that the most important determinants of the nature of interethnic interaction are cultural factors such as religion and language affiliation. The analysis of the dynamics of language shift through the study of bilingualism and the domains of language usage for different demographic groups revealed a strong correlation between recognition of Russian as a mother tongue among some non-Russian ethnic groups and the declining size of these groups. The main conclusion from this macro-analysis of census data was the hypothesis of the growing importance of social and political factors upon ethnic succession, that ethnic identity is no longer a stable characteristic but has become dynamic in nature. In order to verify this hypothesis Ms. Alexakhina conducted a survey in four regions showing different patterns of interethnic interaction: the Karelian Republic, Buryatiya, the Nenezkii Autonomous Region and Tatarstan. These represented the west, east, north and south of the Russian Federation. Samples for the survey were prepared on the basis of census lists so as to exclude mono-Russian families in favour of mixed and ethnic-minority families. The survey confirmed the significant growth in the importance of ethnic affiliation in the everyday lives of people in the Federation following the de-centralisation of the political and economic spheres. Language was shown to be a key symbol of the consciousness of national distinction, confirmed by the fact that the process of russification has been reversed by the active mastering of the languages of titular nationalities. The results also confirmed that individual ethnic identity has ceased to be a fixed personal characteristic of one's cultural and genetic belonging, and people's social adaptation to the current political, social and economic conditions is also demonstrated in changes in individual ethnic self-identification. In general terms, the dynamic nature of national identity means that ethnic identity is at present acquiring the special features of overall social identity, for which the frequent change of priorities is an inherent feature of a person's life cycle. These are mainly linked with a multi-ethnic environment and high individual social mobility. From her results Ms. Alexakhina concludes that the development of national languages and multi-lingualism, together with the preservation of Russian as a state language, seems to be the most promising path to peaceful coexistence and the development of the national cultures of different ethnic groups within the Russian Federation.

Evaluation of Binocular Eye Trackers and Algorithms for 3D Gaze Interaction in Virtual Reality Environments

Tracking user’s visual attention is a fundamental aspect in novel human-computer interaction paradigms found in Virtual Reality. For example, multimodal interfaces or dialogue-based communications with virtual and real agents greatly benefit from the analysis of the user’s visual attention as a vital source for deictic references or turn-taking signals. Current approaches to determine visual attention rely primarily on monocular eye trackers. Hence they are restricted to the interpretation of two-dimensional fixations relative to a defined area of projection. The study presented in this article compares precision, accuracy and application performance of two binocular eye tracking devices. Two algorithms are compared which derive depth information as required for visual attention-based 3D interfaces. This information is further applied to an improved VR selection task in which a binocular eye tracker and an adaptive neural network algorithm is used during the disambiguation of partly occluded objects.

Gain-of-function mutation S422L in the KCNJ8-encoded cardiac K(ATP) channel Kir6.1 as a pathogenic substrate for J-wave syndromes.

BACKGROUND J-wave syndromes have emerged conceptually to encompass the pleiotropic expression of J-point abnormalities including Brugada syndrome (BrS) and early repolarization syndrome (ERS). KCNJ8, which encodes the cardiac K(ATP) Kir6.1 channel, recently has been implicated in ERS following identification of the functionally uncharacterized missense mutation S422L. OBJECTIVE The purpose of this study was to further explore KCNJ8 as a novel susceptibility gene for J-wave syndromes. METHODS Using polymerase chain reaction, denaturing high-performance liquid chromatography, and direct DNA sequencing, comprehensive open reading frame/splice site mutational analysis of KCNJ8 was performed in 101 unrelated patients with J-wave syndromes, including 87 with BrS and 14 with ERS. Six hundred healthy individuals were examined to assess the allelic frequency for all variants detected. KCNJ8 mutation(s) was engineered by site-directed mutagenesis and coexpressed heterologously with SUR2A in COS-1 cells. Ion currents were recorded using whole-cell configuration of the patch-clamp technique. RESULTS One BrS case and one ERS case hosted the identical missense mutation S422L, which was reported previously. KCNJ8-S422L involves a highly conserved residue and was absent in 1,200 reference alleles. Both cases were negative for mutations in all known BrS and ERS susceptibility genes. K(ATP) current of the Kir6.1-S422L mutation was increased significantly over the voltage range from 0 to 40 mV compared to Kir6.1-WT channels (n = 16-21; P <.05). CONCLUSION These findings further implicate KCNJ8 as a novel J-wave syndrome susceptibility gene and a marked gain of function in the cardiac K(ATP) Kir6.1 channel secondary to KCNJ8-S422L as a novel pathogenic mechanism for the phenotypic expression of both BrS and ERS.

A BAYESIAN APPROACH TO DOSE-RESPONSE ASSESSMENT AND DRUG-DRUG INTERACTION ANALYSIS: APPLICATION TO IN VITRO STUDIES

The considerable search for synergistic agents in cancer research is motivated by the therapeutic benefits achieved by combining anti-cancer agents. Synergistic agents make it possible to reduce dosage while maintaining or enhancing a desired effect. Other favorable outcomes of synergistic agents include reduction in toxicity and minimizing or delaying drug resistance. Dose-response assessment and drug-drug interaction analysis play an important part in the drug discovery process, however analysis are often poorly done. This dissertation is an effort to notably improve dose-response assessment and drug-drug interaction analysis. The most commonly used method in published analysis is the Median-Effect Principle/Combination Index method (Chou and Talalay, 1984). The Median-Effect Principle/Combination Index method leads to inefficiency by ignoring important sources of variation inherent in dose-response data and discarding data points that do not fit the Median-Effect Principle. Previous work has shown that the conventional method yields a high rate of false positives (Boik, Boik, Newman, 2008; Hennessey, Rosner, Bast, Chen, 2010) and, in some cases, low power to detect synergy. There is a great need for improving the current methodology. We developed a Bayesian framework for dose-response modeling and drug-drug interaction analysis. First, we developed a hierarchical meta-regression dose-response model that accounts for various sources of variation and uncertainty and allows one to incorporate knowledge from prior studies into the current analysis, thus offering a more efficient and reliable inference. Second, in the case that parametric dose-response models do not fit the data, we developed a practical and flexible nonparametric regression method for meta-analysis of independently repeated dose-response experiments. Third, and lastly, we developed a method, based on Loewe additivity that allows one to quantitatively assess interaction between two agents combined at a fixed dose ratio. The proposed method makes a comprehensive and honest account of uncertainty within drug interaction assessment. Extensive simulation studies show that the novel methodology improves the screening process of effective/synergistic agents and reduces the incidence of type I error. We consider an ovarian cancer cell line study that investigates the combined effect of DNA methylation inhibitors and histone deacetylation inhibitors in human ovarian cancer cell lines. The hypothesis is that the combination of DNA methylation inhibitors and histone deacetylation inhibitors will enhance antiproliferative activity in human ovarian cancer cell lines compared to treatment with each inhibitor alone. By applying the proposed Bayesian methodology, in vitro synergy was declared for DNA methylation inhibitor, 5-AZA-2'-deoxycytidine combined with one histone deacetylation inhibitor, suberoylanilide hydroxamic acid or trichostatin A in the cell lines HEY and SKOV3. This suggests potential new epigenetic therapies in cell growth inhibition of ovarian cancer cells.

Mutual Information for Testing Gene-Environment Interaction

Despite current enthusiasm for investigation of gene-gene interactions and gene-environment interactions, the essential issue of how to define and detect gene-environment interactions remains unresolved. In this report, we define gene-environment interactions as a stochastic dependence in the context of the effects of the genetic and environmental risk factors on the cause of phenotypic variation among individuals. We use mutual information that is widely used in communication and complex system analysis to measure gene-environment interactions. We investigate how gene-environment interactions generate the large difference in the information measure of gene-environment interactions between the general population and a diseased population, which motives us to develop mutual information-based statistics for testing gene-environment interactions. We validated the null distribution and calculated the type 1 error rates for the mutual information-based statistics to test gene-environment interactions using extensive simulation studies. We found that the new test statistics were more powerful than the traditional logistic regression under several disease models. Finally, in order to further evaluate the performance of our new method, we applied the mutual information-based statistics to three real examples. Our results showed that P-values for the mutual information-based statistics were much smaller than that obtained by other approaches including logistic regression models.

A review on continuous wave functional near-infrared spectroscopy and imaging instrumentation and methodology

This year marks the 20th anniversary of functional near-infrared spectroscopy and imaging (fNIRS/fNIRI). As the vast majority of commercial instruments developed until now are based on continuous wave technology, the aim of this publication is to review the current state of instrumentation and methodology of continuous wave fNIRI. For this purpose we provide an overview of the commercially available instruments and address instrumental aspects such as light sources, detectors and sensor arrangements. Methodological aspects, algorithms to calculate the concentrations of oxy- and deoxyhemoglobin and approaches for data analysis are also reviewed. From the single-location measurements of the early years, instrumentation has progressed to imaging initially in two dimensions (topography) and then three (tomography). The methods of analysis have also changed tremendously, from the simple modified Beer-Lambert law to sophisticated image reconstruction and data analysis methods used today. Due to these advances, fNIRI has become a modality that is widely used in neuroscience research and several manufacturers provide commercial instrumentation. It seems likely that fNIRI will become a clinical tool in the foreseeable future, which will enable diagnosis in single subjects.

Effects of Thoratec pulsatile ventricular assist device (PVAD) timing on the abdominal aortic wave intensity pattern

Arterial waves are seen as possible independent mediators of cardiovascular risks, and the wave intensity analysis (WIA) has therefore been proposed as a method for patient selection for ventricular assist device (VAD) implantation. Interpreting measured wave intensity (WI) is challenging and complexity is increased by the implantation of a VAD. The waves generated by the VAD interact with the waves generated by the native heart, and this interaction varies with changing VAD settings. Eight sheep were implanted with a pulsatile VAD (PVAD) through ventriculo-aortic cannulation. The start of PVAD ejection was synchronized to the native R-wave and delayed between 0 % - 90 % of the cardiac cycle in 10 % steps or phase shifts (PS). Pressure and velocity signals were registered, using a combined Doppler and pressure wire positioned in the abdominal aorta, and used to calculate the WI. Depending on the PS, different wave interference phenomena occurred. Maximum unloading of the left ventricle (LV) coincided with constructive interference and maximum blood flow pulsatility, and maximum loading of the LV coincided with destructive interference and minimum blood flow pulsatility. We believe, that non-invasive WIA could potentially be used clinically to assess the mechanical load of the LV, and to monitor the peripheral hemodynamics such as blood flow pulsatility and risk of intestinal bleeding.

Kinetics and kinematics of the tölt: effects of rider interaction and shoeing manipulations

Introduction . Compared to most equine horse breeds which are able to walk, trot and canter /gallop, the gait repertoire of the Icelandic horses additionally includes the lateral gait tölt and frequently also the pace. With respect to the tölt gait, special shoeing, saddling and riding techniques have been developed for Icelandic horses in order to enhance its expressiveness and regularity. Toes are left unnaturally long and heavy shoes and paddings, as well as weighted boots are used to enforce the individual gait predisposition. For the same reason, the rider is placed more caudally to the horse's centre of mass as compared to other riding techniques. The biomechanical impact of these methods on the health of the locomotor system has so far never been subject of systematic research. Objectives . The aims of the presented study are (1) to describe the kinetic and kinematic characteristics of the tölt performed on a treadmill, (2) to understand the mechanical consequences of shoeing manipulation (long hooves, weighted boots) on the loading and protraction movement of the limbs, as well as (3) to study the pressure distribution and effects on the gait pattern of 3 different saddle types used for riding Icelandic horses. Materials and methods . Gait analysis was carried out in 13 Icelandic horses at walk and at slow and medium tölting and trotting speeds on a high-speed treadmill instrumented for measuring vertical ground reaction forces as well as temporal and spatial gait variables. Kinematic data of horse, rider and saddle were measured simultaneously. Gait analysis was first carried out with high, long hooves (SH) without and in combination with weighted boots (ad aim (2)). Afterwards, horses were re-shod according to current horseshoeing standards (SN) and gait analysis was repeated (ad aims (1) and (2)). In a second trial, horses were additionally equipped with a pressure sensitive saddle mat and were ridden with a dressage-like saddle (SDres), an Icelandic saddle (Slcel) and a saddle cushion (SCush) in the standard saddle position (ad aim 3). Results and conclusions . Compared to trot at the same speed, tölting horses had a higher stride rate and lower stride impulses. At the tölt loading of the forelimbs was increased in form of higher peak vertical forces (Fzpeak) due to shorter relative stance durations (StDrel). Conversely, in the hindlimbs, longer StDrel resulted in lower Fzpeak. Despite the higher head-neck position at tölt, there was no measurable shift in weight to the hindlimbs. Footfall rhythm was in most horses laterally coupled at the tölt and frequently had a slight fourbeat and a very short suspension phase at trot; underlining the fact that performance of correct gaits in Icelandic horses needs special training. Gait performance as it is currently judged in competition could be improved using a shoeing with SH, resulting in a 21 ± 5 mm longer dorsal hoof wall, but also a weight gain of 273 ± 50 g at the distal limb due to heavier shoeing material. Compared to SN, SH led to a lower stride rate, a longer stride length and a higher, but not wider, forelimb protraction arc, which were also positively associated with speed. At the tölt, the footfall rhythm showed less tendency to lateral couplets and at the trot, the suspension phase was longer. However, on the long term, SH may have negative implications for the health of the palmar structures of the distal foot by increased limb impulses, higher torques at breakover (up to 20%); as well as peak vertical forces at faster speeds. Compared to the shoeing style, the saddle type had less influence on limb forces or movements. The slight weight shift to the rear with SCush and Slcel may be explained by the more caudal position of the rider relative to the horse's back. With SCush, pressure was highest under the cranial part of the saddle, whereas the saddles with trees had more pressure under the caudal area.

Push and Pull Motivations for Quitting: A three-wave investigation of predictors and consequences of turnover

We report a new analysis of data from a multi-year study, some of which were previously published in the current journal. A longitudinal sample of 380 computer specialists was followed over two years, yielding three measures each of job satisfaction, organizational commitment, and turnover intentions, as well as actual turnover, and reasons for leaving, at Times 2 and 3. Career paths were more diverse than the classical distinction between stayers and leavers implies. Furthermore, although the largest single group of leavers cited “push” reasons, conforming to the classical withdrawal model, a sizable number were attracted to another job (“pull motivation”). In a three-wave structural equation model, job (dis)satisfaction predicted turnover, while organizational commitment exerted its influence only via its association with job satisfaction. As expected, however, attitudes predicted turnover only for participants with push motivation. Quitting, in turn, predicted an improvement in both satisfaction and commitment, indicating that it paid off for the individual. The necessity to study consequences of turnover and to distinguish between different subgroups of stayers and leavers is emphasized.

Interaction of small molecules with specific immune receptors: the p-i concept and its consequences

Drugs may stimulate the immune system by forming stable new antigenic complexes consisting of the drug or drug metabolite which is covalently bound to a protein or peptide (hapten-carrier complex). Both, B- and T-cell immunity may arise, the latter directed to hapten modified peptides presented by HLA molecules. Beside this immunological stimulation, drugs can also stimulate the immune system through binding by non-covalent bonds to proteins like immune receptors. This so-called “pharmacological interaction with immune receptors” concept (“p-i concept”) may occur with HLA or TCR molecules themselves (p-i HLA or p-i TCR), and not the immunogenic peptide. It is a type of “off-target” activity of the drug on immune receptors, but more complex as various cell types, cell interactions and functionally different T cells are involved. In this review the conditions which lead to activation of T cells by p-i are discussed: important factors for a functional consequence of drug binding is the location of binding (p-i HLA or p-i TCR); the exact site within these immune receptors; the affinity of binding and the finding that p-i HLA can stimulate the immune system like an allo-allele. The p-i concept is able to solve some puzzles of drug hypersensitivity reactions and are a basis to better treat and potentially avoid drug hypersensitivity reactions. Moreover, the p-i concept shows that in contrast to previous beliefs small molecules do interact with immune receptors with functional consequence. But these interactions are not based on “immune recognition”, are at odds with some immunological concepts, but may nevertheless open new possibilities to understand and even treat immune reactions