Dose-response resistance to HIV-1/MuLV pseudotype virus ex vivo in a hairpin ribozyme transgenic mouse model

We have investigated the efficacy of a hairpin ribozyme targeting the 5′ leader sequence of HIV-1 RNA in a transgenic model system. Primary spleen cells derived from transgenic or control mice were infected with HIV-1/MuLV pseudotype virus. A significantly reduced susceptibility to infection in ribozyme-expressing transgenic spleen cells (P = 0.01) was shown. Variation of transgene-expression levels between littermates revealed a dose response between ribozyme expression and viral resistance, with an estimated cut off value below 0.2 copies of hairpin ribozyme per cell. These findings open up possibilities for studies on ribozyme efficacy and anti-HIV-1 gene therapy.

Approximate solution for frequency synchronization in a finite-size Kuramoto model

Peer reviewed

A model for amplification of hair-bundle motion by cyclical binding of Ca2+ to mechanoelectrical-transduction channels

Amplification of auditory stimuli by hair cells augments the sensitivity of the vertebrate inner ear. Cell-body contractions of outer hair cells are thought to mediate amplification in the mammalian cochlea. In vertebrates that lack these cells, and perhaps in mammals as well, active movements of hair bundles may underlie amplification. We have evaluated a mathematical model in which amplification stems from the activity of mechanoelectrical-transduction channels. The intracellular binding of Ca2+ to channels is posited to promote their closure, which increases the tension in gating springs and exerts a negative force on the hair bundle. By enhancing bundle motion, this force partially compensates for viscous damping by cochlear fluids. Linear stability analysis of a six-state kinetic model reveals Hopf bifurcations for parameter values in the physiological range. These bifurcations signal conditions under which the system’s behavior changes from a damped oscillatory response to spontaneous limit-cycle oscillation. By varying the number of stereocilia in a bundle and the rate constant for Ca2+ binding, we calculate bifurcation frequencies spanning the observed range of auditory sensitivity for a representative receptor organ, the chicken’s cochlea. Simulations using prebifurcation parameter values demonstrate frequency-selective amplification with a striking compressive nonlinearity. Because transduction channels occur universally in hair cells, this active-channel model describes a mechanism of auditory amplification potentially applicable across species and hair-cell types.

Fine specificity of the antibody response to myelin basic protein in the central nervous system in multiple sclerosis: the minimal B-cell epitope and a model of its features.

T cells, B cells, and antibody are found in the white matter of the central nervous system in multiple sclerosis. The epitope center for the antibody response to human myelin basic protein (MBP) fits precisely the minimal epitope Pro85-Val-Val-His-Phe-Phe-Lys-Asn-Ile-Val-Thr-Pro96 for that reported for HLA DR2b (DRB1*1501)-restricted T cells that recognize MBP [Wucherpfenning, K.W., Sette, A., Southwood, S., Oseroff, C., Matsui, M., Strominger, J. & Hafler, D. (1994) J. Exp. Med. 179, 279-290], and overlaps with the reported DR2a-restricted epitope for T cells reactive to MBP [Martin, R., Howell, M. D., Jaraquemada, D., Furlage, M., Richert, J., Brostoff, S., Long, E. O., McFarlin, D. E. & McFarland, H. F. (1991) J. Exp. Med. 173, 19-24]. We describe a molecular model of this epitope.

Variability of the ocean heat content during the last millennium - an assessment with the ECHO-g Model

Studies addressing climate variability during the last millennium generally focus on variables with a direct influence on climate variability, like the fast thermal response to varying radiative forcing, or the large-scale changes in atmospheric dynamics (e. g. North Atlantic Oscillation). The ocean responds to these variations by slowly integrating in depth the upper heat flux changes, thus producing a delayed influence on ocean heat content (OHC) that can later impact low frequency SST (sea surface temperature) variability through reemergence processes. In this study, both the externally and internally driven variations of the OHC during the last millennium are investigated using a set of fully coupled simulations with the ECHO-G (coupled climate model ECHAMA4 and ocean model HOPE-G) atmosphere-ocean general circulation model (AOGCM). When compared to observations for the last 55 yr, the model tends to overestimate the global trends and underestimate the decadal OHC variability. Extending the analysis back to the last one thousand years, the main impact of the radiative forcing is an OHC increase at high latitudes, explained to some extent by a reduction in cloud cover and the subsequent increase of short-wave radiation at the surface. This OHC response is dominated by the effect of volcanism in the preindustrial era, and by the fast increase of GHGs during the last 150 yr. Likewise, salient impacts from internal climate variability are observed at regional scales. For instance, upper temperature in the equatorial Pacific is controlled by ENSO (El Nino Southern Oscillation) variability from interannual to multidecadal timescales. Also, both the Pacific Decadal Oscillation (PDO) and the Atlantic Multidecadal Oscillation (AMO) modulate intermittently the interdecadal OHC variability in the North Pacific and Mid Atlantic, respectively. The NAO, through its influence on North Atlantic surface heat fluxes and convection, also plays an important role on the OHC at multiple timescales, leading first to a cooling in the Labrador and Irminger seas, and later on to a North Atlantic warming, associated with a delayed impact on the AMO.

A model intercomparison of changes in the Atlantic thermohaline circulation in response to increasing atmospheric CO2 concentration

As part of the Coupled Model Intercomparison Project, integrations with a common design have been undertaken with eleven different climate models to compare the response of the Atlantic thermohaline circulation ( THC) to time-dependent climate change caused by increasing atmospheric CO2 concentration. Over 140 years, during which the CO2 concentration quadruples, the circulation strength declines gradually in all models, by between 10 and 50%. No model shows a rapid or complete collapse, despite the fairly rapid increase and high final concentration of CO2. The models having the strongest overturning in the control climate tend to show the largest THC reductions. In all models, the THC weakening is caused more by changes in surface heat flux than by changes in surface water flux. No model shows a cooling anywhere, because the greenhouse warming is dominant.

The European Union’s Response to Piracy: Are the Lessons Learned in the Horn of Africa a Model for the Gulf of Guinea? EU Diplomacy Paper/2015

The European Union (EU) is seen as the leading actor in successfully fighting piracy around the Horn of Africa. As a global trade power with strong economic interests, the EU is also challenged by similar maritime security threats in the Gulf of Guinea. To date, there has been no comprehensive analysis to assess the potential transfer of successful EU instruments from the Horn of Africa to the piracy situation in West African waters. This paper examines to what extent the EU can draw on its experience made in the Horn of Africa to deter piracy in West African waters. Based on qualitative research interviews, lessons learned from East Africa are identified and subsequently applied to the situation in the Gulf of Guinea. The results show that the EU is only partially drawing on its experience made in the Horn of Africa. One the one hand, it is rather reluctant to use crisis management instruments such as naval operations. On the other hand, the EU is drawing on its successful leadership in international political and military cooperation from around the Horn of Africa in order to make more effective use of available resources in the Gulf of Guinea.

RRREG: Stata module to estimate linear probability model for randomized response data

rrreg fits a linear probability model for randomized response data

Age model of sediment core V20-120 (Table 2)

Time series analyses of atmospheric and oceanic variables in a late Pleistocene record from the northwest Pacific show the complex relationship of the response of various segments of the climate system to changes in the earth's orbit. Most variance spectra of time series from this subarctic record contain frequency peaks with periods corresponding to at least one of the major orbital components of eccentricity, obliquity, or precession. Although the radiolarian faunal (water mass) assemblages have prominent spectral peaks with 41,000-year periods which are coherent with obliquity at this frequency, only the Transitional faunal assemblage contains variance focused at a frequency corresponding to the 100,000-year period of eccentricity. Three of these faunal time series also show variance concentrated at a frequency with a 20,000-year period. These three time series are not coherent at a 20,000-year frequency with either of the dominant spectral peaks of precession. They are coherent, however, with variations in the second harmonic of the obliquity cycle. Changes in obliquity apparently affect siliceous faunal abundances in the northwest Pacific region of this high-latitude site more than variations in eccentricity or precession. Maxima in the time series of quartz abundance occur during low values of eccentricity and high glacial ice volume. Because atmospheric winds serve as the major source of supply of quartz to the sediments at this site, these high quartz values reflect increased aridity at the source region. Except for short periods during interglacials, the characteristics of the surface waters in this region of the subarctic Pacific during much of the last 460,000 years were similar to those which exist today in the Sea of Okhotsk. The spectrum of winter sea surface temperature estimates, derived from siliceous microfaunal abundances, contains dominant frequency peaks at periods of 100,000, 41,000, and 23,000 years which are coherent with eccentricity, obliquity, and precession, respectively. Based upon the relationship of the Subarctic Front with the dominance of specific faunal asemblages, the front was positioned south of its present-day location throughout much of the late Pleistocene.

The Great Lakes as a test model for profile response to sea level changes /

"December 1984."

Los Angeles and Long Beach Harbors model study : resonant response of the harbors for Phase 1 of the Los Angeles deep-draft dry bulk export terminal /

"January 1984."

Los Angeles and Long Beach harbors model study : Deep-Draft Dry Bulk Export Terminal, alternative no. 6: resonant response and tidal circulation studies /

"July 1985."

Analytical modeling of driver response in crash avoidance maneuvering. Volume II: an interactive tire model for driver/vehicle simulation. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Analytical modeling of driver response in crash avoidance maneuvering. Volume III: a trim model and computer program for determining ground vehicle steady state operating conditions and quasilinear stability coefficients. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Wave response of the proposed harbor at Agat, Guam : numerical model investigation /

"March 1987."