The length of time's arrow

An unresolved problem in physics is how the thermodynamic arrow of time arises from an underlying time reversible dynamics. We contribute to this issue by developing a measure of time-symmetry breaking, and by using the work fluctuation relations, we determine the time asymmetry of recent single molecule RNA unfolding experiments. We define time asymmetry as the Jensen-Shannon divergence between trajectory probability distributions of an experiment and its time-reversed conjugate. Among other interesting properties, the length of time's arrow bounds the average dissipation and determines the difficulty of accurately estimating free energy differences in nonequilibrium experiments

Comparison of Intraoperative Fluoroscopy to Postoperative Weight-Bearing Radiographs Obtained 4 to 6 Weeks After Bunion Repair With A Chevron Osteotomy

Background: During operative treatment of bunions, an attempt is made to correct the hallux valgus angle (HVA) and the intermetatarsal angle (IMA). In this study, the HVA and the IMA were measured using intraoperative C-arm fluoroscopic images obtained during surgical treatment of a bunion with chevron osteotomy. These angles were again measured using weight-bearing radiographs obtained 4 to 6 weeks postoperatively. Methods: At our institution, we reviewed medical records of patients who underwent a bunion repair with chevron osteotomy between January 2013 and October 2017. A total of 26 feet from 24 patients were included. Three authors (ALP, TMH, and RAM) measured the HVA and IMA using intraoperative fluoroscopic images and postoperative weight-bearing radiographs (4 measurements per foot; total, 104 measurements). The authors were blinded to their previous angular measurements and to measurements made by the others. An intraclass correlation coefficient was calculated for the HVA and IMA measurements between groups (ie, intraoperative fluoroscopic images and postoperative radiographs) to determine interobserver reliability. We compared the angles measured by the authors between groups and used a paired t test for statistical evaluation. Results: Interobserver difference of the HVA and IMA was low between intraoperative fluoroscopic images and postoperative weight-bearing radiographs (0.98 and 0.79; 0.78 and 0.95, respectively). The measured IMAs were relatively consistent between groups (6.21° and 6.37°, respectively); only two patients had a difference \u3e 3°. There was a greater difference in HVAs between groups (11.5° and 14.2°, respectively). In 11 feet, the HVA was \u3e 5° (range, 5.3-12.7°) in the postoperative radiograph compared to the fluoroscopic image. In one foot, we noted a 7° decrease of the HVA on the postoperative radiograph. The average difference of HVA between groups was 2.6° (P \u3c 0.0001), whereas the IMA was 0.16° (P = 0.002). Conclusions: Interobserver measurements of the HVA and IMA were reliable on both the intraoperative fluoroscopic images and the postoperative weightbearing radiographs. The IMA was similar between groups; however, the HVA was often greater on the postoperative weight-bearing radiographs

The pentameric complex drives immunologically covert cell -cell transmission of wild-type human cytomegalovirus

Human cytomegalovirus (HCMV) strains that have been passaged in vitro rapidly acquire mutations that impact viral growth. These laboratory-adapted strains of HCMV generally exhibit restricted tropism, produce high levels of cell-free virus, and develop susceptibility to natural killer cells. To permit experimentation with a virus that retained a clinically relevant phenotype, we reconstructed a wild-type (WT) HCMV genome using bacterial artificial chromosome technology. Like clinical virus, this genome proved to be unstable in cell culture; however, propagation of intact virus was achieved by placing the RL13 and UL128 genes under conditional expression. In this study, we show that WT-HCMV produces extremely low titers of cell-free virus but can efficiently infect fibroblasts, epithelial, monocyte-derived dendritic, and Langerhans cells via direct cell–cell transmission. This process of cell–cell transfer required the UL128 locus, but not the RL13 gene, and was significantly less vulnerable to the disruptive effects of IFN, cellular restriction factors, and neutralizing antibodies compared with cell-free entry. Resistance to neutralizing antibodies was dependent on high-level expression of the pentameric gH/gL/gpUL128–131A complex, a feature of WT but not passaged strains of HCMV

Network Archaeology: Uncovering Ancient Networks from Present-day Interactions

Often questions arise about old or extinct networks. What proteins interacted in a long-extinct ancestor species of yeast? Who were the central players in the Last.fm social network 3 years ago? Our ability to answer such questions has been limited by the unavailability of past versions of networks. To overcome these limitations, we propose several algorithms for reconstructing a network's history of growth given only the network as it exists today and a generative model by which the network is believed to have evolved. Our likelihood-based method finds a probable previous state of the network by reversing the forward growth model. This approach retains node identities so that the history of individual nodes can be tracked. We apply these algorithms to uncover older, non-extant biological and social networks believed to have grown via several models, including duplication-mutation with complementarity, forest fire, and preferential attachment. Through experiments on both synthetic and real-world data, we find that our algorithms can estimate node arrival times, identify anchor nodes from which new nodes copy links, and can reveal significant features of networks that have long since disappeared.Comment: 16 pages, 10 figure

Networked buffering: a basic mechanism for distributed robustness in complex adaptive systems

A generic mechanism - networked buffering - is proposed for the generation of robust traits in complex systems. It requires two basic conditions to be satisfied: 1) agents are versatile enough to perform more than one single functional role within a system and 2) agents are degenerate, i.e. there exists partial overlap in the functional capabilities of agents. Given these prerequisites, degenerate systems can readily produce a distributed systemic response to local perturbations. Reciprocally, excess resources related to a single function can indirectly support multiple unrelated functions within a degenerate system. In models of genome:proteome mappings for which localized decision-making and modularity of genetic functions are assumed, we verify that such distributed compensatory effects cause enhanced robustness of system traits. The conditions needed for networked buffering to occur are neither demanding nor rare, supporting the conjecture that degeneracy may fundamentally underpin distributed robustness within several biotic and abiotic systems. For instance, networked buffering offers new insights into systems engineering and planning activities that occur under high uncertainty. It may also help explain recent developments in understanding the origins of resilience within complex ecosystems. \ud \u

Genetically Determined Plasma Lipid Levels and Risk of Diabetic Retinopathy: A Mendelian Randomization Study.

Results from observational studies examining dyslipidemia as a risk factor for diabetic retinopathy (DR) have been inconsistent. We evaluated the causal relationship between plasma lipids and DR using a Mendelian randomization approach. We pooled genome-wide association studies summary statistics from 18 studies for two DR phenotypes: any DR (N = 2,969 case and 4,096 control subjects) and severe DR (N = 1,277 case and 3,980 control subjects). Previously identified lipid-associated single nucleotide polymorphisms served as instrumental variables. Meta-analysis to combine the Mendelian randomization estimates from different cohorts was conducted. There was no statistically significant change in odds ratios of having any DR or severe DR for any of the lipid fractions in the primary analysis that used single nucleotide polymorphisms that did not have a pleiotropic effect on another lipid fraction. Similarly, there was no significant association in the Caucasian and Chinese subgroup analyses. This study did not show evidence of a causal role of the four lipid fractions on DR. However, the study had limited power to detect odds ratios less than 1.23 per SD in genetically induced increase in plasma lipid levels, thus we cannot exclude that causal relationships with more modest effect sizes exist

The correlation between reading and mathematics ability at age twelve has a substantial genetic component

Dissecting how genetic and environmental influences impact on learning is helpful for maximizing numeracy and literacy. Here we show, using twin and genome-wide analysis, that there is a substantial genetic component to children’s ability in reading and mathematics, and estimate that around one half of the observed correlation in these traits is due to shared genetic effects (so-called Generalist Genes). Thus, our results highlight the potential role of the learning environment in contributing to differences in a child’s cognitive abilities at age twelve

The Impact of Boundary Spanning Scholarly Publications and Patents

Human knowledge and innovation are recorded in two media: scholarly publication and patents. These records not only document a new scientific insight or new method developed, but they also carefully cite prior work upon which the innovation is built.We quantify the impact of information flow across fields using two large citation dataset: one spanning over a century of scholarly work in the natural sciences, social sciences and humanities, and second spanning a quarter century of United States patents.We find that a publication's citing across disciplines is tied to its subsequent impact. In the case of patents and natural science publications, those that are cited at least once are cited slightly more when they draw on research outside of their area. In contrast, in the social sciences, citing within one's own field tends to be positively correlated with impact

The 2dF Galaxy Redshift Survey: spectral types and luminosity functions

We describe the 2dF Galaxy Redshift Survey (2dFGRS) and the current status of the observations. In this exploratory paper, we apply a principal component analysis to a preliminary sample of 5869 galaxy spectra and use the two most significant components to split the sample into five spectral classes. These classes are defined by considering visual classifications of a subset of the 2dF spectra, and also by comparison with high-quality spectra of local galaxies. We calculate a luminosity function for each of the different classes and find that later-type galaxies have a fainter characteristic magnitude, and a steeper faint-end slope. For the whole sample we find M*=−19.7 (for Ω=1, H₀=100 km s⁻¹ Mpc⁻¹), α=−1.3, φ*=0.017. For class 1 (‘early-type’) we find M*=−19.6, α=−0.7, while for class 5 (‘late-type’) we find M*=−19.0, α=−1.7. The derived 2dF luminosity functions agree well with other recent luminosity function estimates