Indicators of replicative damage in equine tendon fibroblast monolayers

<p>Background: Superficial digital flexor tendon (SDFT) injuries of horses usually follow cumulative matrix microdamage; it is not known why the reparative abilities of tendon fibroblasts are overwhelmed or subverted. Relevant in vitro studies of this process require fibroblasts not already responding to stresses caused by the cell culture protocols. We investigated indicators of replicative damage in SDFT fibroblast monolayers, effects of this on their reparative ability, and measures that can be taken to reduce it.</p> <p>Results: We found significant evidence of replicative stress, initially observing consistently large numbers of binucleate (BN) cells. A more variable but prominent feature was the presence of numerous gammaH2AX (γH2AX) puncta in nuclei, this being a histone protein that is phosphorylated in response to DNA double-stranded breaks (DSBs). Enrichment for injury detection and cell cycle arrest factors (p53 (ser15) and p21) occurred most frequently in BN cells; however, their numbers did not correlate with DNA damage levels and it is likely that the two processes have different causative mechanisms. Such remarkable levels of injury and binucleation are usually associated with irradiation, or treatment with cytoskeletal-disrupting agents.</p> <p>Both DSBs and BN cells were greatest in subconfluent (replicating) monolayers. The DNA-damaged cells co-expressed the replication markers TPX2/repp86 and centromere protein F. Once damaged in the early stages of culture establishment, fibroblasts continued to express DNA breaks with each replicative cycle. However, significant levels of cell death were not measured, suggesting that DNA repair was occurring. Comet assays showed that DNA repair was delayed in proportion to levels of genotoxic stress.</p> <p>Conclusions: Researchers using tendon fibroblast monolayers should assess their “health” using γH2AX labelling. Continued use of early passage cultures expressing initially high levels of γH2AX puncta should be avoided for mechanistic studies and ex-vivo therapeutic applications, as this will not be resolved with further replicative cycling. Low density cell culture should be avoided as it enriches for both DNA damage and mitotic defects (polyploidy). As monolayers differing only slightly in baseline DNA damage levels showed markedly variable responses to a further injury, studies of effects of various stressors on tendon cells must be very carefully controlled.</p&gt

Reef response to sea-level and environmental changes during the last deglaciation: Integrated Ocean Drilling Program Expedition 310, Tahiti Sea Level

The last deglaciation is characterized by a rapid sea-level rise and coeval abrupt environmental changes. The Barbados coral reef record suggests that this period has been punctuated by two brief intervals of accelerated melting (meltwater pulses, MWP), occurring at 14.08-13.61 ka and 11.4-11.1 ka (calendar years before present), that are superimposed on a smooth and continuous rise of sea level. Although their timing, magnitude, and even existence have been debated, those catastrophic sea-level rises are thought to have induced distinct reef drowning events. The reef response to sea-level and environmental changes during the last deglacial sea-level rise at Tahiti is reconstructed based on a chronological, sedimentological, and paleobiological study of cores drilled through the relict reef features on the modern forereef slopes during the Integrated Ocean Drilling Program Expedition 310, complemented by results on previous cores drilled through the Papeete reef. Reefs accreted continuously between 16 and 10 ka, mostly through aggradational processes, at growth rates averaging 10 mm yr-1. No cessation of reef growth, even temporary, has been evidenced during this period at Tahiti. Changes in the composition of coralgal assemblages coincide with abrupt variations in reef growth rates and characterize the response of the upward-growing reef pile to nonmonotonous sea-level rise and coeval environmental changes. The sea-level jump during MWP 1A, 16 ± 2 m of magnitude in ~350 yr, induced the retrogradation of shallow-water coral assemblages, gradual deepening, and incipient reef drowning. The Tahiti reef record does not support the occurrence of an abrupt reef drowning event coinciding with a sea-level pulse of ~15 m, and implies an apparent rise of 40 mm yr-1 during the time interval corresponding to MWP 1B at Barbados. © 2012 Geological Society of America

Preparation of atomically clean and flat Si(100) surfaces by low-energy ion sputtering and low-temperature annealing

Si(100) surfaces were prepared by wet-chemical etching followed by 0.3-1.5keV Ar ion sputtering, either at elevated or room temperature. After a brief anneal under ultrahigh vacuum conditions, the resulting surfaces were examined by scanning tunneling microscopy. We find that wet-chemical etching alone cannot produce a clean and flat Si(100) surface. However, subsequent 300eV Ar ion sputtering at room temperature followed by a 973K anneal yields atomically clean and flat Si(100) surfaces suitable for nanoscale device fabrication.Comment: 13 pages, 3 figures, to be published in Applied Surface Scienc

Small-Scale Vertical Movements of Summer Flounder Relative to Diurnal, Tidal, and Temperature Changes

Observation of animal movements on small spatial scales provides a means to understand how large-scale species distributions are established from individual behavioral decisions. Small-scale vertical movements of 14 Summer Flounder Paralichthys dentatus residing in Chesapeake Bay were observed by using depth data collected with archival tags. A generalized linear mixed model was employed to examine the relationship between these vertical movements and environmental covariates such as tidal state, time of day, lunar phase, and temperature. Vertical movements increased with warming water temperatures, and this pattern was most apparent at night and during rising and falling tides. Fish generally exhibited greater vertical movements at night, but the difference between vertical movements in the day and those at night decreased as fish increased in size. Results from this study fill a void in understanding the small-scale movements of Summer Flounder and could be incorporated into individual-based models to investigate how species distributions develop in response to environmental conditions

Termination of a continent-margin upwelling system at the Permian-Triassic boundary (Opal Creek, Alberta, Canada)

Models of mass extinctions caused by greenhouse warming depend on the ability of warming to affect the oxygenation of the ocean, either through slowing circulation or changes in biological productivity and the organic carbon budget. Opal Creek, Alberta, Canada is a biostratigraphically continuous Permian–Triassic Boundary (PTB) section deposited in deep water on an outer shelf setting in the vast and understudied Panthalassic Ocean, along the western margin of Pangaea. The latest-Permian extinction is here represented as the disappearance of the previously dominant benthic fauna (siliceous sponges). On the basis of nitrogen and reduced sulfur isotopes as well as productivity-sensitive trace elements, the Middle Permian at Opal Creek is interpreted as a highly productive coastal upwelling zone where vigorous denitrification and sulfate reduction occurred in a mid-water oxygen minimum. Similar conditions appear to have continued into the latest Permian until the onset of a euxinic episode represented by a discrete pyrite bed and several trace element indicators of high productivity. This euxinic pulse is followed by the extinction of benthic fauna and a shift in nitrogen and sulfur isotopes to more normal marine values, suggesting the cessation of coastal upwelling and the consequent weakening of the mid-water oxygen minimum. The Lower Triassic appears to be a dysoxic, relatively unproductive environment with a bottom water oxygen minimum. Rhenium–osmium isotope systematics show a minimum of radiogenic Os near the main extinction event, which may be due to volcanic input, and increasingly radiogenic values approaching the PTB, possibly due to increased continental erosion. The Opal Creek system demonstrates that, while the biogeochemical crisis in the latest Permian was capable of impacting the coastal upwelling modality of ocean circulation, a transient increase in productivity likely drove the system toward euxinia and, ultimately, extinction

Theory of asymmetric non-additive binary hard-sphere mixtures

We show that the formal procedure of integrating out the degrees of freedom of the small spheres in a binary hard-sphere mixture works equally well for non-additive as it does for additive mixtures. For highly asymmetric mixtures (small size ratios) the resulting effective Hamiltonian of the one-component fluid of big spheres, which consists of an infinite number of many-body interactions, should be accurately approximated by truncating after the term describing the effective pair interaction. Using a density functional treatment developed originally for additive hard-sphere mixtures we determine the zero, one, and two-body contribution to the effective Hamiltonian. We demonstrate that even small degrees of positive or negative non-additivity have significant effect on the shape of the depletion potential. The second virial coefficient $B_2$, corresponding to the effective pair interaction between two big spheres, is found to be a sensitive measure of the effects of non-additivity. The variation of $B_2$ with the density of the small spheres shows significantly different behavior for additive, slightly positive and slightly negative non-additive mixtures. We discuss the possible repercussions of these results for the phase behavior of binary hard-sphere mixtures and suggest that measurements of $B_2$ might provide a means of determining the degree of non-additivity in real colloidal mixtures

Сутність адміністративного права за новою класифікацією юриспруденції

На основі новітніх підходів до розумінні завдань, об’єктів і класифікації юридичних наук запропонована перспектива розвитку адміністративного права і процесу, які повинні трансформуватися в нові юридичні науки: базисноантиделыктне «Адміністра­тивне право України», процедурне «Админо­регламентное право України» та у низку регулятивних юридичних наук, а також розробити Адміністративний кодекс України, Адміно-регламентній кодекс України, відповідні регулятивні кодекси.На основе новейших подходов к понимании задач, объектов и классификации юридических наук предложена перспектива развития административного права и процес­са, которые должны трансформироваться в новые юридические науки: базисноанти­деликтное «Административное право Украины», процедурное «Админо­регламентное право Украины» и ряд регулятивных юридических наук, а также разработать Административный кодекс Украины, Админо-регламентный кодекс Украины, соответствую­щие регулятивные кодексы.On the basis of the newest fittings to for understanding of tasks, objects and classification of legal sciences the prospect of development of administrative law and process is offered, which must be transformed in new legal sciences: basisuntidelictical the «Administrative law of Ukraine», procedural «Administrative-reglamental law of Ukraine» and the row of regulative legal sciences, and also to develop the Administrative code of Ukraine, Administrative­-reglamental code of Ukraine, proper regulative codes

Transient early wheeze and lung function in early childhood associated with chronic obstructive pulmonary disease genes

Background It has been hypothesized that a disturbed early lung development underlies the susceptibility to chronic obstructive pulmonary disease (COPD). Little is known about whether subjects genetically predisposed to COPD show their first symptoms or reduced lung function in c

Leptonic and Semileptonic Decays of Charm and Bottom Hadrons

We review the experimental measurements and theoretical descriptions of leptonic and semileptonic decays of particles containing a single heavy quark, either charm or bottom. Measurements of bottom semileptonic decays are used to determine the magnitudes of two fundamental parameters of the standard model, the Cabibbo-Kobayashi-Maskawa matrix elements $V_{cb}$ and $V_{ub}$. These parameters are connected with the physics of quark flavor and mass, and they have important implications for the breakdown of CP symmetry. To extract precise values of $|V_{cb}|$ and $|V_{ub}|$ from measurements, however, requires a good understanding of the decay dynamics. Measurements of both charm and bottom decay distributions provide information on the interactions governing these processes. The underlying weak transition in each case is relatively simple, but the strong interactions that bind the quarks into hadrons introduce complications. We also discuss new theoretical approaches, especially heavy-quark effective theory and lattice QCD, which are providing insights and predictions now being tested by experiment. An international effort at many laboratories will rapidly advance knowledge of this physics during the next decade.Comment: This review article will be published in Reviews of Modern Physics in the fall, 1995. This file contains only the abstract and the table of contents. The full 168-page document including 47 figures is available at http://charm.physics.ucsb.edu/papers/slrevtex.p