How good was the profitability of British Railways, 1870-1912?

This paper provides new estimates of the return on capital employed (ROCE) for major British railway companies. It shows that ROCE was generally below the cost of capital after the mid-1870s and fell till the turn of the century. Addressing issues of cost inefficiency could have restored ROCE to an adequate level in the late 1890s but not in 1910. Declines in ROCE hit share prices and returns to shareholders were negative after 1897. Optimal portfolio analysis shows that, whilst railway securities would have had a substantial weight prior to this date, investors would have been justified in rushing to the exits thereafter

Ccdc11 is a novel centriolar satellite protein essential for ciliogenesis and establishment of left-right asymmetry

The establishment of left–right (L-R) asymmetry in vertebrates is dependent on the sensory and motile functions of cilia during embryogenesis. Mutations in CCDC11 disrupt L-R asymmetry and cause congenital heart disease in humans, yet the molecular and cellular functions of the protein remain unknown. Here we demonstrate that Ccdc11 is a novel component of centriolar satellites—cytoplasmic granules that serve as recruitment sites for proteins destined for the centrosome and cilium. Ccdc11 interacts with core components of satellites, and its loss disrupts the subcellular organization of satellite proteins and perturbs primary cilium assembly. Ccdc11 colocalizes with satellite proteins in human multiciliated tracheal epithelia, and its loss inhibits motile ciliogenesis. Similarly, depletion of CCDC11 in Xenopus embryos causes defective assembly and motility of cilia in multiciliated epidermal cells. To determine the role of CCDC11 during vertebrate development, we generated mutant alleles in zebrafish. Loss of CCDC11 leads to defective ciliogenesis in the pronephros and within the Kupffer’s vesicle and results in aberrant L-R axis determination. Our results highlight a critical role for Ccdc11 in the assembly and function of motile cilia and implicate centriolar satellite–associated proteins as a new class of proteins in the pathology of L-R patterning and congenital heart disease

INFORMATION CONTENT OF COYOTE BARKS HOWLS

The information content of coyote (Canis latrans) vocalizations is poorly understood, but has important implications for understanding coyote behavior. Coyotes probably use information present in barks or howls to recognize individuals, but the presence of individually-specific information has not bean demonstrated. We found that coyote barks and howls contained individually specific characteristics: discriminant analysis correctly classified barks of five coyotes 69% of the time and howls of six coyotes 83% of the time. We also investigated the stability of vocalization characteristics at multiple distances from the source. Recordings were played back and re-recorded at 10 m, 600m, and 1,000m. Vocalization features were measured at each distance and analyzed to determine whether characteristics were stable. Most howl characteristics did not change with distance, and regardless of the distance discriminant analysis was 81% accurate at assigning howls among six individuals. Bark characteristics, however, were less stable and it is unlikely that barks could be used for individual recognition over long distances. The disparate results for the two vocalization types suggest that howls and barks serve separate functions. Howls appear optimized to convey information (i.e. data), while barks seem more suitable for attracting attention and acoustic ranging

Staged and Notched Labyrinth Weir Hydraulics

ABSTRACT: Replacement spillways are frequently required to pass revised and larger design storm events. Generally matching the outflow hydrograph of the existing spillway is also a common design requirement. Labyrinth spillways can increase spillway discharge capacity. Staged and notched sections of crest have been used in design to satisfy discharge hydrograph requirements. However, inadequate hydraulic design information is available specific to staged and notched labyrinth weirs. In this study, the flow characteristics of multiple staged and notched labyrinth weir configurations (laboratory-scale) were tested. Head-discharge relationships were evaluated experimentally and compared with computed results using superposition (predicting the discharge over the upper and lower stages separately and summing). The results of this comparison show that, for all configurations tested, the superposition technique estimated actual discharges by approximately ±10%

Association between bilirubin and cardiovascular disease risk factors: using Mendelian randomization to assess causal inference

Background: Elevated serum bilirubin has been associated with reduced risk of cardiovascular disease (CVD). However, serum bilirubin is also related with several potential confounders related to CVD, such as obesity. Mendelian randomization has been proposed as a method to address challenges to validity from confounding and reverse causality. It utilizes genotype to estimate causal relationships between a gene product and physiological outcomes. In this report, we demonstrate its use in assessing direct causal relations between serum bilirubin levels and CVD risk factors, including obesity, cholesterol, measures of vascular function and blood pressure. Methods: Study subjects included 868 asymptomatic individuals. Study subjects were genotyped at the UGT1A1*28 locus, which is strongly associated with bilirubin levels. Results: Serum bilirubin levels were inversely associated with levels of several cardiovascular disease risk factors, including body mass index (p = 0.003), LDL (p = 0.0005) and total cholesterol (p = 0.0002). In contrast, UGT1A1*28 genotype, a known cause of elevated bilirubin levels, was not significantly associated with any of these traditional CVD risk factors. We did observe an association between genotype and brachial artery diameter (p = 0.003) and cold pressor reactivity (p = 0.01). Conclusions: Our findings imply that the observed association of serum bilirubin levels with body mass index and cholesterol are likely due to confounding and suggest that previously established CVD benefits of increased bilirubin may in part be mediated by the early regulation of vascular structure and reactivity

An algorithmic and information-theoretic approach to multimetric index construction

The use of multimetric indices (MMIs), such as the widely used index of biological integrity (IBI), to measure, track, summarize and infer the overall impact of human disturbance on biological communities has been steadily growing in recent years. Initially, MMIs were developed for aquatic communities using preselected biological metrics as indicators of system integrity. As interest in these bioassessment tools has grown, so have the types of biological systems to which they are applied. For many ecosystem types the appropriate biological metrics to use as measures of biological integrity are not known a priori. As a result, a variety of ad hoc protocols for selecting metrics empirically has developed. However, the assumptions made by proposed protocols have not be explicitly described or justified, causing many investigators to call for a clear, repeatable methodology for developing empirically derived metrics and indices that can be applied to any biological system. An issue of particular importance that has not been sufficiently addressed is the way that individual metrics combine to produce an MMI that is a sensitive composite indicator of human disturbance. In this paper, we present and demonstrate an algorithm for constructing MMIs given a set of candidate metrics and a measure of human disturbance. The algorithm uses each metric to inform a candidate MMI, and then uses information-theoretic principles to select MMIs that capture the information in the multidimensional system response from among possible MMIs. Such an approach can be used to create purely empirical (data-based) MMIs or can, optionally, be influenced by expert opinion or biological theory through the use of a weighting vector to create value-weighted MMIs. We demonstrate the algorithm with simulated data to demonstrate the predictive capacity of the final MMIs and with real data from wetlands from Acadia and Rocky Mountain National Parks. For the Acadia wetland data, the algorithm identified 4 metrics that combined to produce a −0.88 correlation with the human disturbance index. When compared to other methods, we find this algorithmic approach resulted in MMIs that were more predictive and comprise fewer metrics

Mass Models and Sunyaev-Zeldovich Effect Predictions for a Flux Limited Sample of 22 Nearby X-Ray Clusters

We define a 90% complete, volume-limited sample of 31 z<0.1 x-ray clusters and present a systematic analysis of public ROSAT PSPC data on 22 of these objects. Our efforts are undertaken in support of the Penn/OVRO SZE survey, and to this end we present predictions for the inverse Compton optical depth towards all 22 of these clusters. We have performed detailed Monte Carlo simulations to understand the effects of the cluster profile uncertainties on the SZE predictions given the OVRO 5.5-meter telescope beam and switching patterns; we find that the profile uncertainties are one of the least significant components of our error budget for SZE-based distance measurements. We also present baryonic masses and baryon mass fractions derived under the assumption of hydrostatic equilibrium for these 22 clusters. The mean baryonic mass fraction within R_500 \sim 500 h^-1 kpc is (7.02 \pm 0.28) x 10^-2 h^-3/2, or (19.8 \pm 0.8) x 10^-2 for h=0.5. We confirm the Allen et al. (1993) claim of an excess absorbing column density towards Abell 478, but do not find similar anomalies in the other 21 clusters in our sample. We also find some evidence for an excess of soft counts in the ROSAT PSPC data. A measurement of H_o using these models and OVRO SZE determinations will be presented in a second paper.Comment: 51 pages, 6 figures included in text. Added comparison of different cosmologies; accepted for publication in Ap

Toxicokinetic Profiles of α-ketoglutarate Cyanohydrin, a Cyanide Detoxification Product, Following Exposure to Potassium Cyanide

Poisoning by cyanide can be verified by analysis of the cyanide detoxification product, α-ketoglutarate cyanohydrin (α-KgCN), which is produced from the reaction of cyanide and endogenous α-ketoglutarate. Although α-KgCN can potentially be used to verify cyanide exposure, limited toxicokinetic data in cyanide-poisoned animals are available. We, therefore, studied the toxicokinetics of α-KgCN and compared its behavior to other cyanide metabolites, thiocyanate and 2-amino-2-thiazoline-4-carboxylic acid (ATCA), in the plasma of 31 Yorkshire pigs that received KCN (4 mg/mL) intravenously (IV) (0.17 mg/kg/min). α-KgCN concentrations rose rapidly during KCN administration until the onset of apnea, and then decreased over time in all groups with a half-life of 15 min. The maximum concentrations of α-KgCN and cyanide were 2.35 and 30.18 μM, respectively, suggesting that only a small fraction of the administered cyanide is converted to α-KgCN. Although this is the case, the α-KgCN concentration increased \u3e100-fold over endogenous concentrations compared to only a three-fold increase for cyanide and ATCA. The plasma profile of α-KgCN was similar to that of cyanide, ATCA, and thiocyanate. The results of this study suggest that the use of α-KgCN as a biomarker for cyanide exposure is best suited immediately following exposure for instances of acute, high-dose cyanide poisoning