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.

Custos de procedimentos de saúde e associação com nível de atividade física e estado nutricional de idosos hipertensos e diabéticos: análise do Estudo SABE - Saúde, Bem-estar e Envelhecimento, 2010

Introdução O nível de atividade física (NAF) insuficiente e estado nutricional (EN) inadequado conferem risco de desenvolvimento de hipertensão arterial e diabete, bem como dificultam o controle destas doenças. Assim, infere-se que os custos despendidos pelo SUS com medicamentos, internações e consultas de hipertensos e diabéticos apresentem relação inversa com NAF, incluindo a prática de caminhada e EN. Entretanto, estudos epidemiológicos que descrevam estes custos e analisem essas associações na população idosa são inexistentes no Brasil, o que dificulta a fundamentação para a implementação de políticas publicas para a economia de recursos. Objetivo Descrever os custos com procedimentos de saúde de idosos hipertensos e diabéticos e verificar qual a sua associação com NAF e EN, segundo sexo e grupos etários. Métodos A amostra foi constituída por 806 idosos com autorreferência à hipertensão e/ou diabete ( 60 anos) residentes no município de São PauloSP, participantes das três coortes do Estudo Saúde, Bem-estar e Envelhecimento SABE - em 2010. A variável dependente custo total anual (em Reais), foi estimada com base nos dados autorreferidos sobre uso de medicamentos, uso dos serviços ambulatoriais e internações hospitalares, retroativos a um ano da coleta de dados. A variáveis explanatórias: i) NAF foi estimada a partir de entrevista utilizando o International Physical Activity Questionnaire (IPAQ, versão curta), classificando os idosos segundo duração da realização de atividades físicas moderada, em ativos ( 150 minutos/semana) e insuficientemente ativos (< 150 minutos/semana); ii) Prática de caminhada, categorizada segundo frequência semanal: a) 4 dias/ semana; b) 1 a 3 dias/semana; c) não caminha. iii) EN, identificado pelo índice de massa corporal (IMC), classificando os idosos em dois grupos: a) IMC < 28 kg/ m²; b) IMC 28 kg/ m² (excesso de peso); as variáveis de controle foram o sexo, grupos etários (a. 70 anos; b. 65 a 69 anos; c. 60 a 64 anos); estado civil (a. casado; b. outros) e, escolaridade (a. sem escolaridade; b. 1 ano). A descrição dos custos segundo as NAF e EN foi representada pelos valores de média e IC95 por cento , mediana e P25 P75, valores mínimos e máximos. Modelos de regressão logística múltipla foram empregados para analisar as associações entre variáveis dependentes e explanatórias. O nível de significância foi estabelecido em 5 por cento e todas as análises foram realizadas considerando amostras complexas, por meio do software Stata, 13.0. 9 Resultados: A média de custo total anual por pessoa foi de R$ 732,54 e a soma dos custos relativa a 12 meses para os 806 idosos foi de R$ 609.587,20, sempre superiores para idosos em excesso de peso, com NAF insuficiente e para idosos que não caminham. Idosos em excesso de peso apresentaram chance 50 por cento superior de estarem no grupo de maior custo total anual (OR 1.49, IC95 por cento 1.01 2.18) e mais de 70 por cento superior de maior custo com medicamentos (OR 1.71, IC95 por cento 1.18 2.47). A ausência de caminhada significou a chance superior para maiores custos anuais com medicamentos (OR 1.63, IC95 por cento 1.06 2.51) e custos totais (OR 1.82, IC95 por cento 1.17 2.81). Todas as análises ajustadas por sexo e idade. O NAF não se associou aos custos totais e custo com medicamentos (p>0.05). Conclusão: Os custos para o controle de HAS e DM em idosos são altos e se associam inversamente à prática de caminhada e ao estado nutricional, especialmente em relação ao custo com o uso de medicamentos antihipertensivos e hipoglicemiantes.

School Principals' Attitudes Towards Performance Based Compensation

The main objective of this study is to determine the attitudes of school principals regarding a performance based compensation system. This study identifies the attitudes towards specific factors that should be considered in the implementation of a system of performance based compensation. The data have been analyzed to determine if a principal's demographic characteristics affect his/her level of agreement with performance based compensation and the factors for implementation. In addition, this study unveils areas of concern that principals have conveyed regarding the implementation of a performance based compensation system. Data was obtained from 444 public school principals representing 444 schools and 178 districts in the state of Colorado. Measures used in the treatment of the data include descriptive statistics and one-way ANOVA. The major findings of this study were: 1. 82.4% of respondents believe that teachers, principals and administrators should be included in performance based compensation (PBC). 2. The top two indicators that respondents believed should be included in a PBC system are student achievement (88.5%) and teacher evaluations (77.6%) 3. The 3 largest obstacles to PBC that respondents identified are: a. The capacity to link student achievement to teacher evaluations (82.9%) b. Teacher Union Resistance (67.1%) c. Cost (55.9%) 4. Principals in urban, rural and suburban geographic groups disagree about the effects of performance based compensation. 5. The top 5 overall concerns regarding Performance Based Compensation were: a. Concerns regarding effectively using assessment to measure performance of all teachers/equity between teachers b. Concerns regarding evaluation (time for principals to learn, consistency from school to school, time for principals to evaluate, quality of evaluation tool). c. Not in favor of PBC due to philosophical views or concerns about lack of research. d. Concerns regarding the equity between classrooms and districts across the state due to poverty levels and unequal resources. e. Concerns that performance based compensation will result in a decline in teacher collaboration and an increase in competition between teachers. Based upon these findings, the researcher concluded that there is not a strong general acceptance of performance based compensation systems. However, urban principals in Colorado tend to view PBC somewhat more favorably than do principals in suburban or rural areas. Most importantly, systems to link student achievement to teacher evaluation must be collaboratively created to ensure PBC systems are equitable, consistent and fair.

Geochemistry of labile organic matter in sediments and interstitial waters of ODP Sites 107-651 and 107-653

Sediment and interstitial water from Sites 651 and 653 (ODP Leg 107) were investigated by organic geochemical methods to characterize labile organic compound classes (amino compounds and carbohydrates) and to evaluate their progressive diagenetic and thermal degradation in deep-sea sediments. Downhole distribution of dissolved organic carbon (DOC) appears related to redox zones associated with bacterial activity and of diagenetic recrystallization of biogenic tests and not so much to organic matter concentrations in ambient sediments. DOC ranges from 250 to 8300 µmol/L (3-100.1 ppm). Amino acids contribute 10%-0.3% of DOC; carbohydrates range from 78 to 5 µmol/L. Rate of degradation of amino acids by thermal effects and/or bacterial activity at both sites (significantly different in sedimentation rates: average 41 cm/1000 yr in the top 300 m at Site 651, average 3.9 cm/1000 yr in the Pliocene/Quaternary sequence at Site 653 to 220 mbsf) is more dependent on exposure time rather than on the depth within the sediment column. Variability in neutral, acidic, and basic amino acid fractions of total amino acids (with a range of 1.1-0.02 µmol/g sediment; up to 2.5% of organic carbon) varies with carbonate content and by differences in thermal stability of amino acids. Distribution patterns of monosaccharides are interpreted to result from differences in organic matter sources, sedimentation rates, and the degree of organic matter decomposition prior to and subsequent to burial. Total particulate carbohydrates range from 1.82 to 0.21 µmol/g sediment and contribute about 8% to the sedimentary organic matter. Investigation of trace metals in the interstitial waters did not show any correlation of either DOC, amino compounds, or carbohydrates.

Lithology, mineralogy and geochemistry of ODP Hole 118-735B and 176-735B respectively

Ocean Drilling Program (ODP) Hole 735B, located on Atlantis Bank on the Southwest Indian Ridge, penetrated 1508 meters below seafloor with an average recovery of 87%, providing a nearly continuous sample of a significant part of oceanic Layer 3. Based on variations in texture and mineralogy, 12 major lithologic units are recognized in the section, ranging from 39.5 to 354 m thick. The principal lithologies include troctolite, troctolitic gabbro, olivine gabbro and microgabbro, gabbro, gabbronorite and Fe-Ti oxide gabbro, gabbronorite, and microgabbro. Highly deformed mylonites, cataclasites, and amphibole gneisses are locally present, as are small quantities of pyroxenite, anorthositic gabbro, and trondhjemite. Downhole variations in mineral composition, particularly for olivine and clinopyroxene, show a number of cyclic variations. Plagioclase compositions show the widest variations and correspond to different degrees of deformation and alteration as well as primary processes. Downhole chemical variations correspond reasonably well with variations in mineral compositions. Iron and titanium mainly reflect the presence of Fe-Ti oxide gabbros but show some cyclical variations in the lower part of the core where oxide gabbros are sparse. CaO is highly variable but shows a small but consistent increase downhole. MgO is more uniform than CaO and shows a very small downward increase. Sulfur and CO2 contents are generally low, but S shows significant enrichment in lithologic Unit IV, which consists of Fe-Ti oxide gabbro, reflecting the presence of sulfide minerals in the sequence. The lithologic, mineralogical, and geochemical data provided here will allow detailed comparisons with ophiolite sections as well as sections of in situ ocean crust drilled in the future.

Total organic carbon (TOC) on ground bulk and carbonate-free sediment samples of ODP Hole 151-911A

A multiproxy analysis of Hole 911A (Ocean Drilling Program (ODP) Leg 151) drilled on the Yermak Plateau (eastern Arctic Ocean) is used to investigate the behaviour of the Svalbard/Barents Sea ice sheet (SBIS) during late Pliocene and early Pleistocene (~3.0-1.7 Ma) climate changes. Contemporary with the 'Mid-Pliocene (~3 Ma) global warmth' (MPGW), a warmer period lasting ~300 kyr with seasonally ice-free conditions in the marginal eastern Arctic Ocean is assumed to be an important regional moisture source, and possibly one decisive trigger for intensification of the Northern Hemisphere glaciation in the Svalbard/Barents Sea area at ~2.7 Ma. An abrupt pulse of ice-rafted debris (IRD) to the Yermak Plateau at ~2.7 Ma reflects distinct melting of sediment-laden icebergs derived from the SBIS and may indicate the protruding advance of the ice sheet onto the outer shelf. Spectral analysis of the total organic carbon (TOC) record being predominantly of terrigenous/fossil-reworked origin indicates SBIS and possibly Scandinavian Ice Sheet response to incoming solar radiation at obliquity and precession periodicities. The strong variance in frequencies near the 41 kyr obliquity cycle between 2.7 and 1.7 Ma indicates, for the first time in the Arctic Ocean, a close relationship of SBIS growth and decay patterns to the Earth's orbital obliquity amplitudes, which dominated global ice volume variations during late Pliocene/early Pleistocene climate changes.

Macular atrophy in patients with long-term anti-VEGF treatment for neovascular age-related macular degeneration.

PURPOSE To identify the prevalence and progression of macular atrophy (MA) in neovascular age-related macular degeneration (AMD) patients under long-term anti-vascular endothelial growth factor (VEGF) therapy and to determine risk factors. METHOD This retrospective study included patients with neovascular AMD and ≥30 anti-VEGF injections. Macular atrophy (MA) was measured using near infrared and spectral-domain optical coherence tomography (SD-OCT). Yearly growth rate was estimated using square-root transformation to adjust for baseline area and allow for linearization of growth rate. Multiple regression with Akaike information criterion (AIC) as model selection criterion was used to estimate the influence of various parameters on MA area. RESULTS Forty-nine eyes (47 patients, mean age 77 ± 14) were included with a mean of 48 ± 13 intravitreal anti-VEGF injections (ranibizumab:37 ± 11, aflibercept:11 ± 6, mean number of injections/year 8 ± 2.1) over a mean treatment period of 6.2 ± 1.3 years (range 4-8.5). Mean best-corrected visual acuity improved from 57 ± 17 letters at baseline (= treatment start) to 60 ± 16 letters at last follow-up. The MA prevalence within and outside the choroidal neovascularization (CNV) border at initial measurement was 45% and increased to 74%. Mean MA area increased from 1.8 ± 2.7 mm(2) within and 0.5 ± 0.98 mm(2) outside the CNV boundary to 2.7 ± 3.4 mm(2) and 1.7 ± 1.8 mm(2) , respectively. Multivariate regression determined posterior vitreous detachment (PVD) and presence/development of intraretinal cysts (IRCs) as significant factors for total MA size (R(2) = 0.16, p = 0.02). Macular atrophy (MA) area outside the CNV border was best explained by the presence of reticular pseudodrusen (RPD) and IRC (R(2) = 0.24, p = 0.02). CONCLUSION A majority of patients show MA after long-term anti-VEGF treatment. Reticular pseudodrusen (RPD), IRC and PVD but not number of injections or treatment duration seem to be associated with the MA size.

Ilustracion y continuacion a la Curia Philipica y correccion de las citas que en ella se hallan erradas : tratase de la mercancia ... Tomo segundo /

Mode of access: Internet.

Revista universitaria.

Historical abstracts. Part B. Twentieth century abstracts

Annali universali di medicina.

Editors: 1817-39, Annibala Omodei; 1840-Mar. 1856, C. A. Calderini; Apr. 1856- Romolo Griffini.

Romantische Novellen.

"Anmerkungen": v. 1, p. [315]-319; v. 2, p. [327]-330.