First-passage time to clear the way for receptor-ligand binding in a crowded environment

Certain biological reactions, such as receptor-ligand binding at cell-cell interfaces and macromolecules binding to biopolymers, require many smaller molecules crowding a reaction site to be cleared. Examples include the T cell interface, a key player in immunological information processing. Diffusion sets a limit for such cavitation to occur spontaneously, thereby defining a timescale below which active mechanisms must take over. We consider $N$ independent diffusing particles in a closed domain, containing a sub-region with $N_{0}$ particles, on average. We investigate the time until the sub-region is empty, allowing a subsequent reaction to proceed. The first passage time is computed using an efficient exact simulation algorithm and an asymptotic approximation in the limit that cavitation is rare. In this limit, we find that the mean first passage time is sub-exponential, $T \propto e^{N_{0}}/N_{0}^2$. For the case of T cell receptors, we find that stochastic cavitation is exceedingly slow, $10^9$ seconds at physiological densities, however can be accelerated to occur within 5 second with only a four-fold dilution

First-Passage Time to Clear the Way for Receptor-Ligand Binding in a Crowded Environment

Certain biological reactions, such as receptor-ligand binding at cell-cell interfaces and macromolecules binding to biopolymers, require many smaller molecules crowding a reaction site to be cleared. Examples include the T-cell interface, a key player in immunological information processing. Diffusion sets a limit for such cavitation to occur spontaneously, thereby defining a time scale below which active mechanisms must take over. We consider N independent diffusing particles in a closed domain, containing a subregion with N_{0} particles, on average. We investigate the time until the subregion is empty, allowing a subsequent reaction to proceed. The first-passage time is computed using an efficient exact simulation algorithm and an asymptotic approximation in the limit that cavitation is rare. In this limit, we find that the mean first-passage time is subexponential, T∝e^{N_{0}}/N_{0}^{2}. For the case of T-cell receptors, we find that stochastic cavitation is exceedingly slow, 10^{9} s at physiological densities; however, it can be accelerated to occur within 5 s with only a fourfold dilution

Use of isotope dilution method to predict bioavailability of organic pollutants in historically contaminated sediments.

Many cases of severe environmental contamination arise from historical episodes, where recalcitrant contaminants have resided in the environment for a prolonged time, leading to potentially decreased bioavailability. Use of bioavailable concentrations over bulk chemical levels improves risk assessment and may play a critical role in determining the need for remediation or assessing the effectiveness of risk mitigation operations. In this study, we applied the principle of isotope dilution to quantify bioaccessibility of legacy contaminants DDT and PCBs in marine sediments from a Superfund site. After addition of 13C or deuterated analogues to a sediment sample, the isotope dilution reached a steady state within 24 h of mixing. At the steady state, the accessible fraction (E) derived by the isotope dilution method (IDM) ranged from 0.28 to 0.89 and was substantially smaller than 1 for most compounds, indicating reduced availability of the extensively aged residues. A strong linear relationship (R2=0.86) was found between E and the sum of rapid (Fr) and slow (Fs) desorption fractions determined by sequential Tenax desorption. The IDM-derived accessible concentration (Ce) was further shown to correlate closely with tissue residue in the marine benthic polychaete Neanthes arenaceodentata exposed in the same sediments. As shown in this study, the IDM approach involves only a few simple steps and may be readily adopted in laboratories equipped with mass spectrometers. This novel method is expected to be especially useful for historically contaminated sediments or soils, for which contaminant bioavailability may have changed significantly due to aging and other sequestration processes

Modeling of Firn Compaction for Estimating Ice-Sheet Mass Change from Observed Ice-Sheet Elevation Change

Changes in ice-sheet surface elevation are caused by a combination of ice-dynamic imbalance, ablation, temporal variations in accumulation rate, firn compaction and underlying bedrock motion. Thus, deriving the rate of ice-sheet mass change from measured surface elevation change requires information on the rate of firn compaction and bedrock motion, which do not involve changes in mass, and requires an appropriate firn density to associate with elevation changes induced by recent accumulation rate variability. We use a 25 year record of surface temperature and a parameterization for accumulation change as a function of temperature to drive a firn compaction model. We apply this formulation to ICESat measurements of surface elevation change at three locations on the Greenland ice sheet in order to separate the accumulation-driven changes from the ice-dynamic/ablation-driven changes, and thus to derive the corresponding mass change. Our calculated densities for the accumulation-driven changes range from 410 to 610 kg/cu m, which along with 900 kg/cu m for the dynamic/ablation-driven changes gives average densities ranging from 680 to 790 kg/cu m. We show that using an average (or "effective") density to convert elevation change to mass change is not valid where the accumulation and the dynamic elevation changes are of opposite sign

Does Exam-targeted Training Help Village Doctors Pass the Certified (Assistant) Physician Exam and Improve Their Practical Skills? A Cross-sectional Analysis of Village Doctors\u27 Perspectives in Changzhou in Eastern China

Background Quality of health care needs to be improved in rural China. The Chinese government, based on the 1999 Law on Physicians, started implementing the Rural Doctor Practice Regulation in 2004 to increase the percentage of certified physicians among village doctors. Special exam-targeted training for rural doctors therefore was launched as a national initiative. This study examined these rural doctors’ perceptions of whether that training helps them pass the exam and whether it improves their skills. Methods Three counties were selected from the 4 counties in Changzhou City in eastern China, and 844 village doctors were surveyed by a questionnaire in July 2012. Chi-square test and Fisher exact test were used to identify differences of attitudes about the exam and training between the rural doctors and certified (assistant) doctors. Longitudinal annual statistics (1980–2014) of village doctors were further analyzed. Results Eight hundred and forty-four village doctors were asked to participate, and 837 (99.17%) responded. Only 14.93% of the respondents had received physician (assistant) certification. Only 49.45% of the village doctors thought that the areas tested by the certification exam were closely related to the healthcare needs of rural populations. The majority (86.19%) felt that the training program was “very helpful” or “helpful” for preparing for the exam. More than half the village doctors (61.46%) attended the “weekly school”. The village doctors considered the most effective method of learning was “continuous training (40.36%)” . The majority of the rural doctors (89.91%) said they would be willing to participate in the training and 96.87% stated that they could afford to pay up to 2000 yuan for it. Conclusions The majority of village doctors in Changzhou City perceived that neither the certification exam nor the training for it are closely related to the actual healthcare needs of rural residents. Policies and programs should focus on providing exam-preparation training for selected rural doctors, reducing training expenditures, and utilizing web-based methods. The training focused on rural practice should be provided to all village doctors, even certified physicians. The government should also adjust the local licensing requirements to attract and recruit new village doctors

Slow Passage through a Saddle-Node Bifurcation in Discrete Dynamical Systems

We study a discrete non-autonomous system whose autonomous counterpart (with the frozen bifurcation parameter) admits a saddle-node bifurcation, and in which the bifurcation parameter slowly changes in time and is characterized by a sweep rate constant $\epsilon$. The discrete system is more appropriate for modeling realistic systems since only time series data is available. We show that in contrast to its autonomous counterpart, when the time mesh size $\Delta t$ is less than the order $O(\epsilon)$, there is a bifurcation delay as the bifurcation time-varying parameter is varied through the bifurcation point, and the delay is proportional to the two-thirds power of the sweep rate constant $\epsilon$. This bifurcation delay is significant in various realistic systems since it allows one to take necessary action promptly before a sudden collapse or shift to different states. On the other hand, when the time mesh size $\Delta t$ is larger than the order $o(\epsilon)$, the dynamical behavior of the solution is dramatically changed before the bifurcation point. This behavior is not observed in the autonomous counterpart. Therefore, the dynamical behavior of the system strongly depends on the time mesh size. Finally. due to the very discrete feature of the system, there are no efficient tools for the analytical study of the system. Our approach is elementary and analytical

Extreme Precipitation Estimation with Typhoon Morakot Using Frequency and Spatial Analysis

Typhoon Morakot lashed Taiwan and produced copious amounts of precipitation in 2009. From the point view of hydrological statistics, the impact of the precipitation from typhoon Morakot using a frequency analysis can be analyzed and discussed. The frequency curve, which was fitted mathematically to historical observed data, can be used to estimate the probability of exceedance for runoff events of a certain magnitude. The study integrates frequency analysis and spatial analysis to assess the effect of Typhoon Morakot event on rainfall frequency in the Gaoping River basin of southern Taiwan. First, extreme rainfall data are collected at sixteen stations for durations of 1, 3, 6, 12, and 24 hours and then an appropriate probability distribution was selected to analyze the impact of the extreme hydrological event. Spatial rainfall patterns for a return period of 200-yr with 24-hr duration with and without Typhoon Morakot are estimated. Results show that the rainfall amount is significantly different with long duration with and without the event for frequency analysis. Furthermore, spatial analysis shows that extreme rainfall for a return period of 200-yr is highly dependent on topography and is smaller in the southwest than that in the east. The results not only demonstrate the distinct effect of Typhoon Morakot on frequency analysis, but also could provide reference in future planning of hydrological engineering

Dynamic Inland Propagation of Thinning Due to Ice Loss at the Margins of the Greenland Ice Sheet

Mass-balance analysis of the Greenland ice sheet based on surface elevation changes observed by the European Remote-sensing Satellite (ERS) (1992-2002) and Ice, Cloud and land Elevation Satellite (ICESat) (2003-07) indicates that the strongly increased mass loss at lower elevations (<2000 m) of the ice sheet, as observed during 2003-07, appears to induce interior ice thinning at higher elevations. In this paper, we perform a perturbation experiment with a three-dimensional anisotropic ice-flow model (AIF model) to investigate this upstream propagation. Observed thinning rates in the regions below 2000m elevation are used as perturbation inputs. The model runs with perturbation for 10 years show that the extensive mass loss at the ice-sheet margins does in fact cause interior thinning on short timescales (i.e. decadal). The modeled pattern of thinning over the ice sheet agrees with the observations, which implies that the strong mass loss since the early 2000s at low elevations has had a dynamic impact on the entire ice sheet. The modeling results also suggest that even if the large mass loss at the margins stopped, the interior ice sheet would continue thinning for 300 years and would take thousands of years for full dynamic recovery

Mass Balance of the West Antarctic Ice-Sheet from ICESat Measurements

Mass balance estimates for 2003-2008 are derived from ICESat laser altimetry and compared with estimates for 1992-2002 derived from ERS radar altimetry. The net mass balance of 3 drainage systems (Pine Island, Thwaites/Smith, and the coast of Marie Bryd) for 2003-2008 is a loss of 100 Gt/yr, which increased from a loss of 70 Gt/yr for the earlier period. The DS including the Bindschadler and MacAyeal ice streams draining into the Ross Ice Shelf has a mass gain of 11 Gt/yr for 2003-2008, compared to an earlier loss of 70 Gt/yr. The DS including the Whillans and Kamb ice streams has a mass gain of 12 Gt/yr, including a significant thickening on the upper part of the Kamb DS, compared to a earlier gain of 6 Gt/yr (includes interpolation for a large portion of the DS). The other two DS discharging into the Ronne Ice Shelf and the northern Ellsworth Coast have a mass gain of 39 Gt/yr, compared to a gain of 4 Gt/yr for the earlier period. Overall, the increased losses of 30 Gt/yr in the Pine Island, Thwaites/Smith, and the coast of Marie Bryd DSs are exceeded by increased gains of 59 Gt/yr in the other 4 DS. Overall, the mass loss from the West Antarctic ice sheet has decreased to 38 Gt/yr from the earlier loss of 67 Gt/yr, reducing the contribution to sea level rise to 0.11 mm/yr from 0.19 mm/y