Liposomally trapped AraCTP to overcome AraC resistance in a murine lymphoma in vitro.

Two cell lines, one sensitive and one resistant to the cytotoxic effects of cytosine arabinoside (AraC) were studied in vitro as a drug-resistance model. The sensitivity of these cell lines, to the effects of free and liposomally trapped AraC and AraCTP as well as empty liposomes alone and mixed with free drug, was studied. This was done by following the inhibition of [3H]-dT incorporation into cellular DNA during exposure to the various drugs and liposomes. Some of the liposomal-lipid compositions inhibited [3H]-dT incorporation at very low concentrations, which made them unsuitable for further study. Liposomes composed of a 7:2:1 molar ratio of phosphatidylcholine:cholesterol:phosphatidic acid were selected as a suitable non-inhibitory carrier. Sensitivity of the two cell lines to free AraC differed by 3 logs, when compared in the [3H]-dT-incorporation assay. The resistant cell line was studied further, and was found to be up to 2 logs more sensitive to AraCTP when given in liposomes than to either the free drug alone or mixed with empty liposomes. It appears from these studies that liposomes are able to help overcome drug resistance in this cell line in vitro

An Assessment to Benchmark the Seismic Performance of a Code-Conforming Reinforced-Concrete Moment-Frame Building

This report describes a state-of-the-art performance-based earthquake engineering methodology that is used to assess the seismic performance of a four-story reinforced concrete (RC) office building that is generally representative of low-rise office buildings constructed in highly seismic regions of California. This “benchmark” building is considered to be located at a site in the Los Angeles basin, and it was designed with a ductile RC special moment-resisting frame as its seismic lateral system that was designed according to modern building codes and standards. The building’s performance is quantified in terms of structural behavior up to collapse, structural and nonstructural damage and associated repair costs, and the risk of fatalities and their associated economic costs. To account for different building configurations that may be designed in practice to meet requirements of building size and use, eight structural design alternatives are used in the performance assessments. Our performance assessments account for important sources of uncertainty in the ground motion hazard, the structural response, structural and nonstructural damage, repair costs, and life-safety risk. The ground motion hazard characterization employs a site-specific probabilistic seismic hazard analysis and the evaluation of controlling seismic sources (through disaggregation) at seven ground motion levels (encompassing return periods ranging from 7 to 2475 years). Innovative procedures for ground motion selection and scaling are used to develop acceleration time history suites corresponding to each of the seven ground motion levels. Structural modeling utilizes both “fiber” models and “plastic hinge” models. Structural modeling uncertainties are investigated through comparison of these two modeling approaches, and through variations in structural component modeling parameters (stiffness, deformation capacity, degradation, etc.). Structural and nonstructural damage (fragility) models are based on a combination of test data, observations from post-earthquake reconnaissance, and expert opinion. Structural damage and repair costs are modeled for the RC beams, columns, and slabcolumn connections. Damage and associated repair costs are considered for some nonstructural building components, including wallboard partitions, interior paint, exterior glazing, ceilings, sprinkler systems, and elevators. The risk of casualties and the associated economic costs are evaluated based on the risk of structural collapse, combined with recent models on earthquake fatalities in collapsed buildings and accepted economic modeling guidelines for the value of human life in loss and cost-benefit studies. The principal results of this work pertain to the building collapse risk, damage and repair cost, and life-safety risk. These are discussed successively as follows. When accounting for uncertainties in structural modeling and record-to-record variability (i.e., conditional on a specified ground shaking intensity), the structural collapse probabilities of the various designs range from 2% to 7% for earthquake ground motions that have a 2% probability of exceedance in 50 years (2475 years return period). When integrated with the ground motion hazard for the southern California site, the collapse probabilities result in mean annual frequencies of collapse in the range of [0.4 to 1.4]x10 -4 for the various benchmark building designs. In the development of these results, we made the following observations that are expected to be broadly applicable: (1) The ground motions selected for performance simulations must consider spectral shape (e.g., through use of the epsilon parameter) and should appropriately account for correlations between motions in both horizontal directions; (2) Lower-bound component models, which are commonly used in performance-based assessment procedures such as FEMA 356, can significantly bias collapse analysis results; it is more appropriate to use median component behavior, including all aspects of the component model (strength, stiffness, deformation capacity, cyclic deterioration, etc.); (3) Structural modeling uncertainties related to component deformation capacity and post-peak degrading stiffness can impact the variability of calculated collapse probabilities and mean annual rates to a similar degree as record-to-record variability of ground motions. Therefore, including the effects of such structural modeling uncertainties significantly increases the mean annual collapse rates. We found this increase to be roughly four to eight times relative to rates evaluated for the median structural model; (4) Nonlinear response analyses revealed at least six distinct collapse mechanisms, the most common of which was a story mechanism in the third story (differing from the multi-story mechanism predicted by nonlinear static pushover analysis); (5) Soil-foundation-structure interaction effects did not significantly affect the structural response, which was expected given the relatively flexible superstructure and stiff soils. The potential for financial loss is considerable. Overall, the calculated expected annual losses (EAL) are in the range of $52,000 to$97,000 for the various code-conforming benchmark building designs, or roughly 1% of the replacement cost of the building ($8.8M). These losses are dominated by the expected repair costs of the wallboard partitions (including interior paint) and by the structural members. Loss estimates are sensitive to details of the structural models, especially the initial stiffness of the structural elements. Losses are also found to be sensitive to structural modeling choices, such as ignoring the tensile strength of the concrete (40 EAL) or the contribution of the gravity frames to overall building stiffness and strength (15 change in EAL). Although there are a number of factors identified in the literature as likely to affect the risk of human injury during seismic events, the casualty modeling in this study focuses on those factors (building collapse, building occupancy, and spatial location of building occupants) that directly inform the building design process. The expected annual number of fatalities is calculated for the benchmark building, assuming that an earthquake can occur at any time of any day with equal probability and using fatality probabilities conditioned on structural collapse and based on empirical data. The expected annual number of fatalities for the code-conforming buildings ranges between 0.05*10 -2 and 0.21*10 -2 , and is equal to 2.30*10 -2 for a non-code conforming design. The expected loss of life during a seismic event is perhaps the decision variable that owners and policy makers will be most interested in mitigating. The fatality estimation carried out for the benchmark building provides a methodology for comparing this important value for various building designs, and enables informed decision making during the design process. The expected annual loss associated with fatalities caused by building earthquake damage is estimated by converting the expected annual number of fatalities into economic terms. Assuming the value of a human life is$3.5M, the fatality rate translates to an EAL due to fatalities of $3,500 to$5,600 for the code-conforming designs, and $79,800 for the non-code conforming design. Compared to the EAL due to repair costs of the code-conforming designs, which are on the order of$66,000, the monetary value associated with life loss is small, suggesting that the governing factor in this respect will be the maximum permissible life-safety risk deemed by the public (or its representative government) to be appropriate for buildings. Although the focus of this report is on one specific building, it can be used as a reference for other types of structures. This report is organized in such a way that the individual core chapters (4, 5, and 6) can be read independently. Chapter 1 provides background on the performance-based earthquake engineering (PBEE) approach. Chapter 2 presents the implementation of the PBEE methodology of the PEER framework, as applied to the benchmark building. Chapter 3 sets the stage for the choices of location and basic structural design. The subsequent core chapters focus on the hazard analysis (Chapter 4), the structural analysis (Chapter 5), and the damage and loss analyses (Chapter 6). Although the report is self-contained, readers interested in additional details can find them in the appendices

Stress and Predation Impacts on North American Quail Translocations

Translocations have been used in attempts to bolster or restore native quail populations for \u3e150 years, often with little success. However, with some northeastern United States quail populations undetectable or extirpated, and others across the United States on the extreme decline, translocation as a tool for quail population restoration is becoming increasingly popular. Two factors contributing to translocation failure are physiological stress and predation. Chronic stress associated with translocations can result in weight loss, reduced immune system function, suppressed reproduction, and an altered fight-or-flight response. These stress-induced responses increase vulnerability to predation, the primary cause of quail mortality. Here, we review the relationship between quail translocations, stress, and predation, and recommend future research and best practices to mitigate the impacts of stress and predation on translocated quail. To improve future translocation outcomes, more research is needed on stress mitigation throughout the translocation process (capture, handling, transport, and release). While capture and handling are unavoidably stressful, there is greater potential to reduce stress levels during holding and transport. Recent validation of fecal corticosterone metabolites as a non-invasive method to quantify stress in quail offers a useful tool for testing stress reduction protocols. Preliminary experimental results regarding nutritional supplements and stress levels are inconclusive, but enrichment during temporary holding and access to travel rations may help improve survival in long-distance (\u3e800 km) translocations. We also recommend predator control at release sites, particularly for raccoons (Procyon lotor) and other mesomammals

The Crustal Rigidity of a Neutron Star, and Implications for PSR 1828-11 and other Precession Candidates

We calculate the crustal rigidity parameter, b, of a neutron star (NS), and show that b is a factor 40 smaller than the standard estimate due to Baym & Pines (1971). For a NS with a relaxed crust, the NS's free-precession frequency is directly proportional to b. We apply our result for b to PSR 1828-11, a 2.5 Hz pulsar that appears to be precessing with period 511 d. Assuming this 511-d period is set by crustal rigidity, we show that this NS's crust is not relaxed, and that its reference spin (roughly, the spin for which the crust is most relaxed) is 40 Hz, and that the average spindown strain in the crust is 5 \times 10^{-5}. We also briefly describe the implications of our b calculation for other well-known precession candidates.Comment: 44 pages, 10 figures, submitted to Ap

LISA, binary stars, and the mass of the graviton

We extend and improve earlier estimates of the ability of the proposed LISA (Laser Interferometer Space Antenna) gravitational wave detector to place upper bounds on the graviton mass, m_g, by comparing the arrival times of gravitational and electromagnetic signals from binary star systems. We show that the best possible limit on m_g obtainable this way is ~ 50 times better than the current limit set by Solar System measurements. Among currently known, well-understood binaries, 4U1820-30 is the best for this purpose; LISA observations of 4U1820-30 should yield a limit ~ 3-4 times better than the present Solar System bound. AM CVn-type binaries offer the prospect of improving the limit by a factor of 10, if such systems can be better understood by the time of the LISA mission. We briefly discuss the likelihood that radio and optical searches during the next decade will yield binaries that more closely approach the best possible case.Comment: ReVTeX 4, 6 pages, 1 figure, submitted to Phys Rev

Graphene as Transparent Electrode for Direct Observation of Hole Photoemission from Silicon to Oxide

The outstanding electrical and optical properties of graphene make it an excellent alternative as a transparent electrode. Here we demonstrate the application of graphene as collector material in internal photoemission (IPE) spectroscopy; enabling the direct observation of both electron and hole injections at a Si/Al2O3 interface and successfully overcoming the long-standing difficulty of detecting holes injected from a semiconductor emitter in IPE measurements. The observed electron and hole barrier heights are 3.5 eV and 4.1 eV, respectively. Thus the bandgap of Al2O3 can be further deduced to be 6.5 eV, in close agreement with the valued obtained by vacuum ultraviolet spectroscopic ellipsometry analysis. The detailed optical modeling of a graphene/Al2O3/Si stack reveals that by using graphene in IPE measurements the carrier injection from the emitter is significantly enhanced and the contribution of carrier injection from the collector electrode is minimal. The method can be readily extended to various IPE test structures for a complete band alignment analysis and interface characterization.Comment: 15 pages, 5 figure

Longitudinal changes of spinal cord grey and white matter following spinal cord injury

Objectives: Traumatic and non-traumatic spinal cord injury produce neurodegeneration across the entire neuraxis. However, the spatiotemporal dynamics of spinal cord grey and white matter neurodegeneration above and below the injury is understudied. // Methods: We acquired longitudinal data from 13 traumatic and 3 non-traumatic spinal cord injury patients (8–8 cervical and thoracic cord injuries) within 1.5 years after injury and 10 healthy controls over the same period. The protocol encompassed structural and diffusion-weighted MRI rostral (C2/C3) and caudal (lumbar enlargement) to the injury level to track tissue-specific neurodegeneration. Regression models assessed group differences in the temporal evolution of tissue-specific changes and associations with clinical outcomes. // Results: At 2 months post-injury, white matter area was decreased by 8.5% and grey matter by 15.9% in the lumbar enlargement, while at C2/C3 only white matter was decreased (−9.7%). Patients had decreased cervical fractional anisotropy (FA: −11.3%) and increased radial diffusivity (+20.5%) in the dorsal column, while FA was lower in the lateral (−10.3%) and ventral columns (−9.7%) of the lumbar enlargement. White matter decreased by 0.34% and 0.35% per month at C2/C3 and lumbar enlargement, respectively, and grey matter decreased at C2/C3 by 0.70% per month. // Conclusions: This study describes the spatiotemporal dynamics of tissue-specific spinal cord neurodegeneration above and below a spinal cord injury. While above the injury, grey matter atrophy lagged initially behind white matter neurodegeneration, in the lumbar enlargement these processes progressed in parallel. Tracking trajectories of tissue-specific neurodegeneration provides valuable assessment tools for monitoring recovery and treatment effects

Longitudinal changes of spinal cord grey and white matter following spinal cord injury

Objectives: Traumatic and non-traumatic spinal cord injury produce neurodegeneration across the entire neuraxis. However, the spatiotemporal dynamics of spinal cord grey and white matter neurodegeneration above and below the injury is understudied. Methods: We acquired longitudinal data from 13 traumatic and 3 non-traumatic spinal cord injury patients (8-8 cervical and thoracic cord injuries) within 1.5 years after injury and 10 healthy controls over the same period. The protocol encompassed structural and diffusion-weighted MRI rostral (C2/C3) and caudal (lumbar enlargement) to the injury level to track tissue-specific neurodegeneration. Regression models assessed group differences in the temporal evolution of tissue-specific changes and associations with clinical outcomes. Results: At 2 months post-injury, white matter area was decreased by 8.5% and grey matter by 15.9% in the lumbar enlargement, while at C2/C3 only white matter was decreased (-9.7%). Patients had decreased cervical fractional anisotropy (FA: -11.3%) and increased radial diffusivity (+20.5%) in the dorsal column, while FA was lower in the lateral (-10.3%) and ventral columns (-9.7%) of the lumbar enlargement. White matter decreased by 0.34% and 0.35% per month at C2/C3 and lumbar enlargement, respectively, and grey matter decreased at C2/C3 by 0.70% per month. Conclusions: This study describes the spatiotemporal dynamics of tissue-specific spinal cord neurodegeneration above and below a spinal cord injury. While above the injury, grey matter atrophy lagged initially behind white matter neurodegeneration, in the lumbar enlargement these processes progressed in parallel. Tracking trajectories of tissue-specific neurodegeneration provides valuable assessment tools for monitoring recovery and treatment effects