Dynamical fluctuations in biochemical reactions and cycles

We develop theory for the dynamics and fluctuations in some cyclic and linear biochemical reactions. We use the approach of maximum caliber, which computes the ensemble of paths taken by the system, given a few experimental observables. This approach may be useful for interpreting single-molecule or few-particle experiments on molecular motors, enzyme reactions, ion-channels, and phosphorylation-driven biological clocks. We consider cycles where all biochemical states are observable. Our method shows how: (1) the noise in cycles increases with cycle size and decreases with the driving force that spins the cycle and (2) provides a recipe for estimating small-number features, such as probability of backward spin in small cycles, from experimental data. The back-spin probability diminishes exponentially with the deviation from equilibrium. We believe this method may also be useful for other few-particle nonequilibrium biochemical reaction systems

Apnea, bradycardia and desaturation spells in premature infants: impact of a protocol for the duration of 'spell-free' observation on interprovider variability and readmission rates.

ObjectiveTo study the impact of implementing a protocol to standardize the duration of observation in preterm infants with apnea/bradycardia/desaturation spells before hospital discharge on length of stay (LOS) and readmission rates.Study designA protocol to standardize the duration of in-hospital observation for preterm infants with apnea, bradycardia and desaturation spells who were otherwise ready for discharge was implemented in December 2013. We evaluated the impact of this protocol on the LOS and readmission rates of very low birth weight infants (VLBW). Data on readmission for apnea and an apparent life-threatening event (ALTE) within 30 days of discharge were collected. The pre-implementation epoch (2011 to 2013) was compared to the post-implementation period (2014 to 2016).ResultsThere were 426 and 368 VLBW discharges before and after initiation of the protocol during 2011 to 2013 and 2014 to 2016, respectively. The LOS did not change with protocol implementation (66±42 vs 64±42 days before and after implementation of the protocol, respectively). Interprovider variability on the duration of observation for apneic spells (F-8.8, P=0.04) and bradycardia spells (F-17.4, P<0.001) decreased after implementation of the protocol. The readmission rate for apnea/ALTE after the protocol decreased from 12.1 to 3.4% (P=0.01).ConclusionImplementing an institutional protocol for VLBW infants to determine the duration of apnea/bradycardia/ desaturation spell-free observation period as recommended by the American Academy of Pediatrics clinical report did not prolong the LOS but effectively reduced interprovider variability and readmission rates

Breakdown of Strong-Coupling Perturbation Theory in Doped Mott Insulators

We show that doped Mott insulators, such as the copper-oxide superconductors, are asymptotically slaved in that the quasiparticle weight, $Z$, near half-filling depends critically on the existence of the high energy scale set by the upper Hubbard band. In particular, near half filling, the following dichotomy arises: $Z\ne 0$ when the high energy scale is integrated out but Z=0 in the thermodynamic limit when it is retained. Slavery to the high energy scale arises from quantum interference between electronic excitations across the Mott gap. Broad spectral features seen in photoemission in the normal state of the cuprates are argued to arise from high energy slavery.Comment: Published versio

Second-line antiretroviral therapy in a workplace and community-based treatment programme in South Africa: determinants of virological outcome.

: Background: As antiretroviral treatment (ART) programmes in resource-limited settings mature, more patients are experiencing virological failure. Without resistance testing, deciding who should switch to second-line ART can be difficult. The consequences for second-line outcomes are unclear. In a workplace- and community-based multi-site programme, with 6-monthly virological monitoring, we describe outcomes and predictors of viral suppression on second-line, protease inhibitor-based ART.Methods: We used prospectively collected clinic data from patients commencing first-line ART between 1/1/03 and 31/12/08 to construct a study cohort of patients switched to second-line ART in the presence of a viral load (VL) ?400 copies/ml. Predictors of VL<400 copies/ml within 15 months of switch were assessed using modified Poisson regression to estimate risk ratios.Results: 205 workplace patients (91.7% male; median age 43 yrs) and 212 community patients (38.7% male; median age 36 yrs) switched regimens. At switch compared to community patients, workplace patients had a longer duration of viraemia, higher VL, lower CD4 count, and higher reported non-adherence on first-line ART. Non-adherence was the reported reason for switching in a higher proportion of workplace patients. Following switch, 48.3% (workplace) and 72.0% (community) achieved VL<400, with non-adherence (17.9% vs. 1.4%) and virological rebound (35.6% vs. 13.2% with available measures) reported more commonly in the workplace programme. In adjusted analysis of the workplace programme, lower switch VL and younger age were associated with VL<400. In the community programme, shorter duration of viraemia, higher CD4 count and transfers into programme on ART were associated with VL<400.Conclusion: High levels of viral suppression on second-line ART can be, but are not always, achieved in multi-site treatment programmes with both individual- and programme-level factors influencing outcomes. Strategies to support both healthcare workers and patients during this switch period need to be evaluated; sub-optimal adherence, particularly in the workplace programme must be addressed

Unbiased estimates of galaxy scaling relations from photometric redshift surveys

Many physical properties of galaxies correlate with one another, and these correlations are often used to constrain galaxy formation models. Such correlations include the color-magnitude relation, the luminosity-size relation, the Fundamental Plane, etc. However, the transformation from observable (e.g. angular size, apparent brightness) to physical quantity (physical size, luminosity), is often distance-dependent. Noise in the distance estimate will lead to biased estimates of these correlations, thus compromising the ability of photometric redshift surveys to constrain galaxy formation models. We describe two methods which can remove this bias. One is a generalization of the V_max method, and the other is a maximum likelihood approach. We illustrate their effectiveness by studying the size-luminosity relation in a mock catalog, although both methods can be applied to other scaling relations as well. We show that if one simply uses photometric redshifts one obtains a biased relation; our methods correct for this bias and recover the true relation

Computational design of natural laminar flow wings for transonic transport application

Two research programs are described which directly relate to the application of natural laminar flow (NLF) technology to transonic transport-type wind planforms. Each involved using state-of-the-art computational methods to design three-dimensional wing contours which generate significant runs of favorable pressure gradients. The first program supported the Variable Sweep Transition Flight Experiment and involves design of a full-span glove which extends from the leading edge to the spoiler hinge line on the upper surface of an F-14 outer wing panel. Boundary-layer and static-pressure data will be measured on this design during the supporting wind-tunnel and flight tests. These data will then be analyzed and used to infer the relationship between crossflow and Tollmein-Schlichting disturbances on laminar boundary-layer transition. A wing was designed computationally for a corporate transport aircraft in the second program. The resulting wing design generated favorable pressure gradients from the leading edge aft to the mid-chord on both upper and lower surfaces at the cruise design point. Detailed descriptions of the computational design approach are presented along with the various constraints imposed on each of the designs. Wing surface pressure distributions, which support the design objective and were derived from transonic three-dimensional analyses codes, are also presented. Current status of each of the research programs is included in the summary

How well do CMIP5 climate simulations replicate historical trends and patterns of meteorological droughts?

Assessing the uncertainties and understanding the deficiencies of climate models are fundamental to developing adaptation strategies. The objective of this study is to understand how well Coupled Model Intercomparison-Phase 5 (CMIP5) climate model simulations replicate ground-based observations of continental drought areas and their trends. The CMIP5 multimodel ensemble encompasses the Climatic Research Unit (CRU) ground-based observations of area under drought at all time steps. However, most model members overestimate the areas under extreme drought, particularly in the Southern Hemisphere (SH). Furthermore, the results show that the time series of observations and CMIP5 simulations of areas under drought exhibit more variability in the SH than in the Northern Hemisphere (NH). The trend analysis of areas under drought reveals that the observational data exhibit a significant positive trend at the significance level of 0.05 over all land areas. The observed trend is reproduced by about three-fourths of the CMIP5 models when considering total land areas in drought. While models are generally consistent with observations at a global (or hemispheric) scale, most models do not agree with observed regional drying and wetting trends. Over many regions, at most 40% of the CMIP5 models are in agreement with the trends of CRU observations. The drying/wetting trends calculated using the 3 months Standardized Precipitation Index (SPI) values show better agreement with the corresponding CRU values than with the observed annual mean precipitation rates. Pixel-scale evaluation of CMIP5 models indicates that no single model demonstrates an overall superior performance relative to the other models