Simple mechanochemistry describes the dynamics of kinesin molecules

Recently, Block and coworkers [Visscher, K., Schnitzer, M. J., & Block, S. M. (1999) Nature (London) 400, 184–189 and Schnitzer, M. J., Visscher, K. & Block, S. M. (2000) Nat. Cell Biol. 2, 718–723] have reported extensive observations of individual kinesin molecules moving along microtubules in vitro under controlled loads, F = 1 to 8 pN, with [ATP] = 1 μM to 2 mM. Their measurements of velocity, V, randomness, r, stalling force, and mean run length, L, reveal a need for improved theoretical understanding. We show, presenting explicit formulae that provide a quantitative basis for comparing distinct molecular motors, that their data are satisfactorily described by simple, discrete-state, sequential stochastic models. The simplest (N = 2)-state model with fixed load-distribution factors and kinetic rate constants concordant with stopped-flow experiments, accounts for the global (V, F, L, [ATP]) interdependence and, further, matches relative acceleration observed under assisting loads. The randomness, r(F,[ATP]), is accounted for by a waiting-time distribution, ψ\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}{\mathrm{_{1}^{+}}}\end{equation*}\end{document}(t), [for the transition(s) following ATP binding] with a width parameter ν ≡ 〈t〉2/〈(Δt)2〉≃2.5, indicative of a dispersive stroke of mechanicity ≃0.6 or of a few (≳ν − 1) further, kinetically coupled states: indeed, N = 4 (but not N = 3) models do well. The analysis reveals: (i) a substep of d0 = 1.8–2.1 nm on ATP binding (consistent with structurally based suggestions); (ii) comparable load dependence for ATP binding and unbinding; (iii) a strong load dependence for reverse hydrolysis and subsequent reverse rates; and (iv) a large (≳50-fold) increase in detachment rate, with a marked load dependence, following ATP binding.

Acesso ao tratamento oncológico no município de São Paulo: o câncer de mama como condição traçadora

Acompanhando a tendência mundial, o Brasil apresenta um processo de envelhecimento de sua população, caracterizado pelo aumento das condições crônicas, inclusive do câncer. O quadro convoca mudanças profundas nos sistemas de saúde, demandando a implantação de Redes de Atenção, a fim de garantir acesso a todos os níveis de atenção, superando a fragmentação do cuidado. Com o intuito de conhecer os avanços no que se refere à atenção oncológica em rede, analisou-se o acesso ao tratamento do câncer em São Paulo, especialmente a partir do surgimento da Lei dos sessenta dias. Foram considerados os sistemas de monitoramento da atenção oncológica no município, além de analisados os itinerários assistenciais de usuárias, utilizando o câncer de mama como condição traçadora. Não foi possível identificar uma redução do tempo de espera para iniciar o tratamento, a partir do banco do Registro Hospitalar de Câncer de são Paulo, considerando que não há completude na base a partir de 2013, sendo observado que o tempo indicado na lei foi ultrapassado nos dois anos anteriores. Da mesma forma, notou-se um aumento da proporção de estádios avançados nesse período. Ainda com relação à variável tempo, as informações no SIGA demonstraram que, em 2013, o tempo médio para uma consulta em Onco-mastologia nos serviços de gestão municipal que estão sob regulação foi de apenas 4 dias. Por meio dos Sistemas de Informação Ambulatorial e Hospitalar, observou-se um aumento estatisticamente significativo na produção de radioterapia e de cirurgias oncológicas entre os anos 2011 e 2014, e uma tendência de redução dos procedimentos quimioterápicos. O Sistema de Informação sobre Câncer de Mama demonstrou aumento no percentual de mamografias alteradas, aspecto que, ao ser analisado em conjunto com o aumento da proporção de estadiamentos avançados, pode ser indicativo de maior dificuldade no acesso ao diagnóstico precoce do câncer de mama. Observou-se que a judicialização esteve muito relacionada a acesso a medicamentos quimioterápicos, de prescrição após a entrada nos serviços especializados, o que confirma que o acesso ao tratamento de câncer de mama no município não apresenta grandes barreiras. Um importante efeito visualizado com o surgimento da Lei foi a padronização dos protocolos de acesso aos serviços de gestão municipal e estadual. Entretanto, a rede de oncologia em São Paulo continua fragmentada dentre seus componentes estruturais, as ações permanecem no plano da construção de fluxos de encaminhamento, ficando restrita à atenção especializada. A atenção oncológica na cidade é atravessada pelo setor privado, o que deixa na dependência dos prestadores a disponibilização de vagas para acesso e o fluxo interno de cada serviço. O poder ainda continua com os grandes prestadores, não sendo bem conhecidos os caminhos para o acesso a algumas instituições, nem publicizadas as informações sobre fila e tempo de espera. A legislação sozinha não é indutora de melhoria de acesso, nem muito menos de garantia de integralidade. Um importante desafio para o SUS é a integração dos serviços e a construção de redes de atenção com centralidade na APS, garantindo, acima de tudo, o diagnóstico em tempo oportuno e a efetiva gestão sobre os serviços privados contratados de média e alta complexidade.

Avaliação do prognóstico com a utilização de dois escores de mortalidade em terapia intensiva pediátrica de nível de atendimento terciário

A redução da mortalidade é um objetivo fundamental das unidades de terapia intensiva pediátrica (UTIP). O estágio de gravidade da doença reflete a magnitude das comorbidades e distúrbios fisiológicos no momento da internação e pode ser avaliada pelos escores prognósticos de mortalidade. Os dois principais escores utilizados na UTIP são o Pediatric Risk of Mortality (PRISM) e o Pediatric Index of Mortality (PIM). O PRISM utiliza os piores valores de variáveis fisiológicas e laboratoriais nas primeiras 24 horas de internação enquanto o PIM2 utiliza dados da primeira hora de internação na UTIP e apenas uma gasometria arterial. Não há consenso na literatura, entre PRISM e PIM2, quanto à utilidade e padronização na admissão na terapia intensiva para as crianças e adolescentes, principalmente em uma UTI de nível de atendimento terciário. O objetivo do estudo foi estabelecer o escore de melhor performance na avaliação do prognóstico de mortalidade que seja facilmente aplicável na rotina da UTIP, para ser utilizado de forma padronizada e contínua. Foi realizado um estudo retrospectivo onde foram revisados os escores PRISM e PIM2 de 359 pacientes internados na unidade de terapia intensiva pediátrica do Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da USP, considerada uma unidade de atendimento de nível terciário. A mortalidade foi de 15%, o principal tipo de admissão foi clinico (78%) sendo a principal causa de internação a disfunção respiratória (37,3%). Os escores dos pacientes que foram a óbito mostraram-se maiores do que o dos sobreviventes. Para o PRISM foi 15 versus 7 (p = 0,0001) e para o PIM2, 11 versus 5 (p = 0,0002), respectivamente. Para a amostra geral, o Standardized Mortality Ratio (SMR) subestimou a mortalidade tanto para o PIM2 quanto para o PRISM [1,15 (0,84 - 1,46) e 1,67 (1,23 - 2,11), respectivamente]. O teste de Hosmer-Lemeshow mostrou calibração adequada para ambos os escores [x2 = 12,96 (p = 0,11) para o PRISM e x2 = 13,7 (p = 0,09) para o PIM2]. A discriminação, realizada por meio da área sob a curva ROC, foi mais adequada para o PRISM do que para o PIM2 [0,76 (IC 95% 0,69 - 0,83) e 0,65 (IC 95% 0,57 - 0,72), respectivamente, p= 0,002]. No presente estudo, a melhor sensibilidade e especificidade para o risco de óbito do PRISM foi um escore entre 13 e 14, mostrando que, com o avanço tecnológico, o paciente precisa ter um escore mais elevado, ou seja, maior gravidade clínica do que a população original, para um maior risco de mortalidade. Os escores de gravidade podem ter seus resultados modificados em consequência: do sistema de saúde (público ou privado), da infraestrutura da UTIP (número de leitos, recursos humanos, parque tecnológico) e indicação da internação. A escolha de um escore de gravidade depende das características individuais da UTIP, como o tempo de espera na emergência, presença de doença crônica complexa (por exemplo, pacientes oncológicos) e como é realizado o transporte para a UTIP. Idealmente, estudos multicêntricos têm maior significância estatística. No entanto, estudos com populações maiores e mais homogêneas, especialmente nos países em desenvolvimento, são difíceis de serem realizados

Consumer trial, continuous use, and economic benefits of a retail service innovation:the case of the personal shopping assistant

Service innovations in retailing have the potential to benefit consumers as well as retailers. This research models key factors associated with the trial and continuous use of a specific self-service technology (SST), the personal shopping assistant (PSA), and estimates retailer benefits from implementing that innovation. Based on theoretical insights from prior SST studies, diffusion of innovation literature, and the technology acceptance model (TAM), this study develops specific hypotheses and tests them on a sample of 104 actual users of the PSA and 345 nonusers who shopped at the retail store offering the PSA device. Results indicate that factors affecting initial trial are different from those affecting continuous use. More specifically, consumers' trust toward the retailer, novelty seeking, and market mavenism are positively related to trial, while technology anxiety hinders the likelihood of trying the PSA. Perceived ease of use of the device positively impacts continuous use while consumers' need for interaction in shopping environments reduces the likelihood of continuous use. Importantly, there is evidence on retailer benefits from introducing the innovation since consumers using the PSA tend to spend more during each shopping trip. However, given the high costs of technology, the payback period for recovery of investments in innovation depends largely upon continued use of the innovation by consumers. Important implications are provided for retailers considering investments in new in-store service innovations. Incorporation of technology within physical stores affords opportunities for the retailer to reduce costs, while enhancing service provided to consumers. Therefore, service innovations in retailing have the potential to benefit consumers as well as retailers. This research models key factors associated with the trial and continuous use of a specific SST in the retail context, the PSA, and estimates retailer benefits from implementing that innovation. In so doing, the study contributes to the nascent area of research on SSTs in the retail sector. Based on theoretical insights from prior SST studies, diffusion of innovation literature, and the TAM, this study develops specific hypotheses regarding the (1) antecedent effects of technological anxiety, novelty seeking, market mavenism, and trust in the retailer on trial of the service innovation; (2) the effects of ease of use, perceived waiting time, and need for interaction on continuous use of the innovation; and (3) the effect of use of innovation on consumer spending at the store. The hypotheses were tested on a sample of 104 actual users of the PSA and 345 nonusers who shopped at the retail store offering the PSA device, one of the early adopters of PSA in Germany. Data were analyzed using logistic regression (antecedents of trial), multiple regression (antecedents of continuous use), and propensity score matching (assessing retailer benefits). Results indicate that factors affecting initial trial are different from those affecting continuous use. More specifically, consumers' trust toward the retailer, novelty seeking, and market mavenism are positively related to trial, while technology anxiety hinders the likelihood of trying the PSA. Perceived ease of use of the device positively impacts continuous use, while consumers' need for interaction in shopping environments reduces the likelihood of continuous use. Importantly, there is evidence on retailer benefits from introducing the innovation since consumers using the PSA tend to spend more during each shopping trip. However, given the high costs of technology, the payback period for recovery of investments in innovation depends largely upon continued use of the innovation by consumers. Important implications are provided for retailers considering investments in new in-store service innovations. The study contributes to the literature through its (1) simultaneous examination of antecedents of trial and continuous usage of a specific SST, (2) the demonstration of economic benefits of SST introduction for the retailer, and (3) contribution to the stream of research on service innovation, as against product innovation.

Quality of Service System Approximation in IP Networks

This paper is sponsored by the Ministry of Education and Research of the Republic of Bulgaria in the framework of project No 105 “Multimedia Packet Switching Networks Planning with Quality of Service and Traffic Management”.

Single-Server Queueing System with Markov-Modulated Arrivals and Service Times

Key words: Markov-modulated queues, waiting time, heavy traffic.

Comparison between Numerical and Simulation Methods for Age-dependent Branching Models with Immigration

2000 Mathematics Subject Classification: primary: 60J80, 60J85, secondary: 62M09, 92D40

Limiting Distributions for Lifetimes in Alternating Renewal Processes

2000 Mathematics Subject Classification: 60K05

Estimation of a Regression Function on a Point Process and its Application to Financial Ruin Risk Forecast

2000 Mathematics Subject Classification: Primary 60G55; secondary 60G25.

Preferences of Hungarian consumers for quality, access and price attributes of health care services — result of a discrete choice experiment

In 2010, a household survey was carried out in Hungary among 1037 respondents to study consumer preferences and willingness to pay for health care services. In this paper, we use the data from the discrete choice experiments included in the survey, to elicit the preferences of health care consumers about the choice of health care providers. Regression analysis is used to estimate the effect of the improvement of service attributes (quality, access, and price) on patients’ choice, as well as the differences among the socio-demographic groups. We also estimate the marginal willingness to pay for the improvement in attribute levels by calculating marginal rates of substitution. The results show that respondents from a village or the capital, with low education and bad health status are more driven by the changes in the price attribute when choosing between health care providers. Respondents value the good skills and reputation of the physician and the attitude of the personnel most, followed by modern equipment and maintenance of the office/hospital. Access attributes (travelling and waiting time) are less important. The method of discrete choice experiment is useful to reveal patients’ preferences, and might support the development of an evidence-based and sustainable health policy on patient payments.

Development of a medium-capacity guideway transit planning guide

Rapid population increase and booming economic growth have caused a significant escalation in car ownership in many cities, leading to additional or, multiple traffic problems on congested roadways. The increase of automobiles is generating a significant amount of congestion and pollution in many cities. It has become necessary to find a solution to the ever worsening traffic problems in our cities. Building more roadways is nearly impossible due to the limitations of right-of-way in cities. Studies have shown that guideway transit could provide effective transportation and could stimulate land development. The Medium-Capacity Guideway Transit (MCGT) is one of the alternatives to solve this problem. The objective of this research was to better understand the characteristics of MCGT systems, to investigate the existing MCGT systems around the world and determine the main factors behind the planning of successful systems, and to develop a MCGT planning guide. The factors utilized in this study were determined and were analyzed using Excel. A MCGT Planning Guide was developed using Microsoft Visual Basic. ^ A MCGT was defined as a transit system whose capacity can carry up to 20,000 passengers per hour per direction (pphpd). The results shown that Light Rail Transit (LRT) is favored when peak hour demand is less than 13,000 pphpd. Automated People Mover (APM) is favored when the peak hour demand is more than 18,000 pphpd. APM systems could save up to three times the waiting time cost compared to that of the LRT. If comfort and convenience are important, then using an APM does make sense. However, if cost is the critical factor, then LRT will make more sense because it is reasonable service at a reasonable price. If travel time and safety (accident/crush) costs were included in calculating life-cycle “total” costs, the capital cost advantage of LRT disappeared and APM could become very competitive. The results also included a range of cost-performance criteria for MCGT systems that help planners, engineers, and decision-makers to select the most feasible system for their respective areas. ^

Business process quantitative analysis and optimization for service industries

The total time a customer spends in the business process system, called the customer cycle-time, is a major contributor to overall customer satisfaction. Business process analysts and designers are frequently asked to design process solutions with optimal performance. Simulation models have been very popular to quantitatively evaluate the business processes; however, simulation is time-consuming and it also requires extensive modeling experiences to develop simulation models. Moreover, simulation models neither provide recommendations nor yield optimal solutions for business process design. A queueing network model is a good analytical approach toward business process analysis and design, and can provide a useful abstraction of a business process. However, the existing queueing network models were developed based on telephone systems or applied to manufacturing processes in which machine servers dominate the system. In a business process, the servers are usually people. The characteristics of human servers should be taken into account by the queueing model, i.e. specialization and coordination. ^ The research described in this dissertation develops an open queueing network model to do a quick analysis of business processes. Additionally, optimization models are developed to provide optimal business process designs. The queueing network model extends and improves upon existing multi-class open-queueing network models (MOQN) so that the customer flow in the human-server oriented processes can be modeled. The optimization models help business process designers to find the optimal design of a business process with consideration of specialization and coordination. ^ The main findings of the research are, first, parallelization can reduce the cycle-time for those customer classes that require more than one parallel activity; however, the coordination time due to the parallelization overwhelms the savings from parallelization under the high utilization servers since the waiting time significantly increases, thus the cycle-time increases. Third, the level of industrial technology employed by a company and coordination time to mange the tasks have strongest impact on the business process design; as the level of industrial technology employed by the company is high; more division is required to improve the cycle-time; as the coordination time required is high; consolidation is required to improve the cycle-time. ^

Otimização de parâmetros mecânicos e microestruturais dos moldes em areia de sílica ligados quimicamente pelo processo de cura a frio em fundição de aço

Surface defects on steel parts borne costs of smelting industries due to the need of rework. Sand molds are frequently used in foundry industries and largely responsible for providing surface defects. This study aims to optimize the levels of the molding process variables to minimize the occurrence of surface defects in steel castings in silica sand molds chemically linked by cold cure process. The methodology used the experimental design with split plot, being considered in the study the resin percentage factors in the mold formulation, addition of iron oxide, type of paint, the paint application method, amount of ink layers, use of hot air along the lines and waiting time of the mold before casting. They were analyzed as response variables erosion defects, sand inclusion, penetration, porosity and surface finish. Tensile strength tests were performed to evaluate the influence of factors on mechanical parameters and the microstructural parameters were carried out the analysis of X-ray diffraction, scanning electron microscopy (SEM) and thermal analysis (TG / DSC / dilatometry). The results elucidate that for the faulty erosion, the only significant factor with a 95% confidence level was the type of ink and the ink alumina-based superior results obtained. For the sand inclusion of defect, there were three significant factors, with best results obtained with alumina-based paint and spray applied using hot air in the mold before casting the metal. For the defect penetration, there were four significant factors, the best results being achieved with 0.8% of resin and addition of iron oxide in the molding formulation, the paint being applied by brush and standby time of 24 hours before leak. For the defect porosity with a 95% confidence level, no significant factors. For the defect surface finish, the best results were achieved with the 0.8% formulation of the resin in the mold and application of the paint brush. To obtain the levels of the factors that optimize all defects simultaneously, we performed a weighted average of the results of each type of fault, concluding that the best levels of the factors were: 0.8% resin and addition of iron oxide in the formulation of the template, application of two coats of paint applied with a brush or spray, using hot air in the mold before casting and 24 hours of waiting ready the mold before casting. These levels of the optimized factors were used in an experiment to confirm that ratified the results, helping to reduce rework and consequently reducing costs of cast steel parts.

Fatores pré-abate que influenciam na qualidade da carne de frangos griller

The consumption of a product is directly linked to its quality, and are required to comply with quality standard regulations. In chicken "griller" which comes from industrial strains, selected for best growth performance, shot with up to 35 days old and weighing 1,400kg, they have not been reported in the literature a number of quality aspects This study aimed determine the muscle transformation time in the flesh in chickens "griller" incidence of meat defects, "PSE" (pale, soft and exdudative) and "DFD" (dark, firm and dry) and their correlation between different window times slaughter (total time between beginning of the fasting and the time of slaughter) and pH curve, four different times post mortem. The base data for the study was composed of information of 208 chickens, collected between August and September 2014, in a slaughterhouse slaughtering chickens in the middle region of Triangulo Mineiro and Alto Paranaíba. We used the Minitab 17.1.0 program for the development of descriptive statistical analysis and Pareto charts. The Pearson correlation was used to evaluate the linear relationship between two variables and Excel 2013, Microsoft Office®, to produce tables and graphs. The analysis consisted of 11 chickens cities and the distance to the poultry slaughterhouse ranged from 24.5 km to 123 km. It was observed that the pH curve decays gradually until time 5horas after slaughter, and its increase was 24, indicating the transformation of the muscle meat. The incidence of regular meat was 39.9%, "DFD" 30.3% and "PSE" 29.8%. For "DFD" meat, it was observed that factors: low ambient temperature, longer transportation and fast window and mileage at dirt road, contributed to its occurrence (p <0.05). For "PSE" meat, it was observed that lower body weight factors, longer transport favored frequency (p <0.05) of the meat defect. There was no significant correlation in variance analysis between distance, waiting time at rest shed and humidity related to meat defects (p> 0.05). This high incidence of defects meat may be due to pre-slaughter stress factors.

Group problem-solving skills training for self-harm: randomised controlled trial

Background: Rates of self-harm are high and have recently increased. This trend and the repetitive nature of self-harm pose a significant challenge to mental health services. Aims: To determine the efficacy of a structured group problem-solving skills training (PST) programme as an intervention approach for self-harm in addition to treatment as usual (TAU) as offered by mental health services. Method: A total of 433 participants (aged 18-64 years) were randomly assigned to TAU plus PST or TAU alone. Assessments were carried out at baseline and at 6-week and 6-month follow-up and repeated hospital-treated self-harm was ascertained at 12-month follow-up. Results: The treatment groups did not differ in rates of repeated self-harm at 6-week, 6-month and 12-month follow-up. Both treatment groups showed significant improvements in psychological and social functioning at follow-up. Only one measure (needing and receiving practical help from those closest to them) showed a positive treatment effect at 6-week (P = 0.004) and 6-month (P = 0.01) follow-up. Repetition was not associated with waiting time in the PST group. Conclusions: This brief intervention for self-harm is no more effective than treatment as usual. Further work is required to establish whether a modified, more intensive programme delivered sooner after the index episode would be effective.