The tail of the Jurassic fish Leedsichthys problematicus (Osteichthyes: Actinopterygii) collected by Alfred Nicholson Leeds - an example of the importance of historical records in palaeontology

The specimen of the tail of <i>Leedsichthys problematicus</i>, now in The Natural History Museum, London, was one of the most spectacular fossil vertebrates from the Oxford Clay Formation of Peterborough, but as an isolated find it shares no bones in common with the holotype of the genus and species. However, a letter from Alfred Nicholson Leeds and related documents cast valuable new light on the excavation of the tail, indicating that it was discovered with cranial bones, gill-rakers, and two pectoral fins, thereby including elements that can potentially be compared with those of the holotype. The documents also clearly indicate that The Natural History Museum's specimen is not part of the same individual as any other numbered specimen of <i>Leedsichthys</i> as had been speculated on other occasions. The maximum size of the animal represented by The Natural History Museum's specimen was possibly around 9 metres, considerably less than previous estimates of up to 27.6 metres for <i>Leedsichthys</i>. Historical documentary evidence should therefore be rigorously checked both when studying historical specimens in science, and in preparing text for museum display labels

Safety and feasibility of transcranial direct current stimulation (tDCS) combined with sensorimotor retraining in chronic low back pain: a protocol for a pilot randomised controlled trial

Introduction Chronic low back pain (LBP) is a common and costly health problem yet current treatments demonstrate at best, small effects. The concurrent application of treatments with synergistic clinical and mechanistic effects may improve outcomes in chronic LBP. This pilot trial aims to (1) determine the feasibility, safety and perceived patient response to a combined transcranial direct current stimulation (tDCS) and sensorimotor retraining intervention in chronic LBP and (2) provide data to support a sample size calculation for a fully powered trial should trends of effectiveness be present. Methods and analysis A pilot randomised, assessor and participant-blind, sham-controlled trial will be conducted. Eighty participants with chronic LBP will be randomly allocated to receive either (1) active tDCS + sensorimotor retraining or (2) sham tDCS + sensorimotor retraining. tDCS (active or sham) will be applied to the primary motor cortex for 20 min immediately prior to 60 min of supervised sensorimotor retraining twice per week for 10 weeks. Participants in both groups will complete home exercises three times per week. Feasibility, safety, pain, disability and pain system function will be assessed immediately before and after the 10-week intervention. Analysis of feasibility and safety will be performed using descriptive statistics. Statistical analyses will be conducted based on intention-to-treat and per protocol and will be used to determine trends for effectiveness. Ethics and dissemination Ethical approval has been gained from the institutional human research ethics committee (H10184). Written informed consent will be provided by all participants. Results from this pilot study will be submitted for publication in peer-reviewed journals. Trial registration number ACTRN1261600062448

Assimilating MODIS and AMSR-E Snow Observations in a Snow Evolution Model

In this paper four simple computationally inexpensive, direct insertion data assimilation schemes are presented, and evaluated, to assimilate Moderate Resolution Imaging Spectroradiometer (MODIS) snow cover, which is a binary observation, and Advanced Microwave Scanning Radiometer for Earth Observing System (EOS) (AMSR-E) snow water equivalent (SWE) observations, which are at a coarser resolution than MODIS, into a numerical snow evolution model. The four schemes are 1) assimilate MODIS snow cover on its own with an arbitrary 0.01 m added to the model cells if there is a difference in snow cover; 2) iteratively change the model SWE values to match the AMSR-E equivalent value; 3) AMSR-E scheme with MODIS observations constraining which cells can be changed, when both sets of observations are available; and 4) MODIS-only scheme when the AMSR-E observations are not available, otherwise scheme 3. These schemes are used in the winter of 2006/07 over the southeast corner of Colorado and the tri-state area: Wyoming, Colorado, and Nebraska. It is shown that the inclusion of MODIS data enables the model in the north domain to have a 15% improvement in number of days with a less than 10% disagreement with the MODIS observation 24 h later and approximately 5% for the south domain. It is shown that the AMSR-E scheme has more of an impact in the south domain than the north domain. The assimilation results are also compared to station snow-depth data in both domains, where there is up-to-a-factor-of-5 underestimation of snow depth by the assimilation schemes compared with the station data but the snow evolution is fairly consistent

Is there evidence for export-led adoption of ISO 14001? A review of the literature using meta-regression

Does the export orientation of a firm affect the likelihood that it adopts an environmental management certification? We use meta-regression methods to analyze systematically the corpus of published research on export-led adoption of the largest and most prominent certification, ISO 14001. We show that the explanatory variables authors choose to include in their models reflect the tenets of stakeholder and institutional theories. We also find that the literature suffers from substantial publication bias but that, once this is accounted for appropriately, a genuine effect remains. The evidence from 20 years of published studies taken as a whole is that export does incentivize the adoption of the standard as often hypothesized by proponents of voluntary approaches and self-regulation

Periplasmic depolymerase provides insight into ABC transporter-dependent secretion of bacterial capsular polysaccharides

This work was supported in part by grants from the Canadian Institutes of Health Research (FDN_148364) (to C.W.). S.D.L. is a recipient of a Natural Science and Engineering Research Council Alexander Graham Bell Canada Graduate Scholarship and Michael Smith Foreign Study Supplement. C.W. is a Canada Research Chair. J.H.N. is a Wellcome Trust Investigator (100209/Z/12/Z).Capsules are surface layers of hydrated capsular polysaccharides (CPSs) produced by many bacteria. The human pathogen Salmonella enterica serovar Typhi produces "Vi antigen" CPS, which contributes to virulence. In a conserved strategy used by bacteria with diverse CPS structures, translocation of Vi antigen to the cell surface is driven by an ATP-binding cassette (ABC) transporter. These transporters are engaged in heterooligomeric complexes proposed to form an enclosed translocation conduit to the cell surface, allowing the transporter to power the entire process. We identified Vi antigen biosynthesis genetic loci in genera of the Burkholderiales, which are paradoxically distinguished from S. Typhi by encoding VexL, a predicted pectate lyase homolog. Biochemical analyses demonstrated that VexL is an unusual metal-independent endolyase with an acidic pH optimum that is specific for Oacetylated Vi antigen. A 1.22-Å crystal structure of the VexL-Vi antigen complex revealed features which distinguish common secreted catabolic pectate lyases from periplasmic VexL, which participates in cell-surface assembly. VexL possesses a right-handed parallel beta-superhelix, of which one face forms an electropositive glycan-binding groove with an extensive hydrogen bonding network that includes Vi antigen acetyl groups and confers substrate specificity. VexL provided a probe to interrogate conserved features of the ABC transporter-dependent export model. When introduced into S. Typhi, VexL localized to the periplasm and degraded Vi antigen. In contrast, a cytosolic derivative had no effect unless export was disrupted. These data provide evidence that CPS assembled in ABC transporter-dependent systems is actually exposed to the periplasm during envelope translocation.Publisher PDFPeer reviewe

Non-invasive assessment of murine PD-L1 levels in syngeneic tumor models by nuclear imaging with nanobody tracers

Blockade of the inhibitory PD-1/PD-L1 immune checkpoint axis is a promising cancer treatment. Nonetheless, a significant number of patients and malignancies do not respond to this therapy. To develop a screen for response to PD-1/PD-L1 inhibition, it is critical to develop a non-invasive tool to accurately assess dynamic immune checkpoint expression. Here we evaluated non-invasive SPECT/CT imaging of PD-L1 expression, in murine tumor models with varying PD-L1 expression, using high affinity PD-L1-specific nanobodies (Nbs). We generated and characterized 37 Nbs recognizing mouse PD-L1. Among those, four Nbs C3, C7, E2 and E4 were selected and evaluated for preclinical imaging of PD-L1 in syngeneic mice. We performed SPECT/CT imaging in wild type versus PD-L1 knock-out mice, using Technetium-99m (99mTc) labeled Nbs. Nb C3 and E2 showed specific antigen binding and beneficial biodistribution. Through the use of CRISPR/Cas9 PD-L1 knock-out TC-1 lung epithelial cell lines, we demonstrate that SPECT/CT imaging using Nb C3 and E2 identifies PD-L1 expressing tumors, but not PD-L1 non-expressing tumors, thereby confirming the diagnostic potential of the selected Nbs. In conclusion, these data show that Nbs C3 and E2 can be used to non-invasively image PD-L1 levels in the tumor, with the strength of the signal correlating with PD-L1 levels. These findings warrant further research into the use of Nbs as a tool to image inhibitory signals in the tumor environment

A Dynamic Bayesian Network Approach to Behavioral Modelling of Elderly People during a Home-based Augmented Reality Balance Physiotherapy Programme

In this study, we propose a dynamic Bayesian network (DBN)-based approach to behavioral modelling of community dwelling older adults at risk for falls during the daily sessions of a hologram-enabled vestibular rehabilitation therapy programme. The component of human behavior being modelled is the level of frustration experienced by the user at each exercise, as it is assessed by the NASA Task Load Index. Herein, we present the topology of the DBN and test its inference performance on real-patient data.Clinical Relevance- Precise behavioral modelling will provide an indicator for tailoring the rehabilitation programme to each individual's personal psychological needs

PERFIL PROTÉICO E EFICIÊNCIA REPRODUTIVA DE VACAS DE CORTE EM LACTAÇÃO SUPLEMENTADAS COM URÉIA NO VERÃO

O objetivo do presente estudo foi mensurar os níveis plasmáticos de proteína plasmática total (PPT), albumina e uréia, hematócrito e escore da condição corporal (ECC), visando avaliar o efeito da suplementação com uréia sobre o perfil protéico e o índice de prenhez (IP) de vacas de corte em lactação, mantidas em campo nativo, durante o período de verão. O experimento ocorreu entre setembro/2002 (primavera) e fevereiro/2003 (verão). As matrizes foram divididas aleatoriamente em dois grupos: controle © n=161) e tratado (T) n=159). Os grupos receberam mistura mineral, porém o T, recebeu adicionalmente 10% de uréia agrícola em janeiro e fevereiro. Relativamente a PPT, não foi observada diferença entre T e C, no verão. Na albumina, não foi observada diferença entre primavera e verão. O C apresentou concentrações maiores no verão do que o T. Os valores do hematócrito, no C de verão foram maiores do que os do C da primavera e T de verão. Na uréia o grupo T, no verão, apresentou níveis maiores do que os C de primavera e verão. Não houve diferença nos ECC entre primavera e verão, assim como entre T e C, no verão. Quanto ao IP, não houve diferença entre C e T. Em conclusão, a uréia tem efeitos deletérios sobre o perfil protéico de vacas de corte com cria ao pé, no verão, quando há alta disponibilidade de massa verde. A adição de uréia à mistura mineral não influência a eficiência reprodutiva das matrizes. Protein profile and reproductive efficiency of lactating beef cows, supplemented with urea during the summer Abstract The objective of the present study was to assay total protein (PPT), albumin and urea plasma levels, hematocrit, body conditions score (BCS) and pregnancy rates (PR) in beef cows supplemented or not with urea during the summer. The experiment started in September (spring) 2002 and ended in February (summer) 2003. The dams were randomly assigned in two experimental groups: control (C; n = 161) and treated (T; n = 159). Both groups received a complete mineral mix. For the T group, a total of 10% of agricultural grade urea was added to the mix during January and February. As a result, no differences in PPT has been observed between both experimental groups during the summer. However, in regard to plasmatic albumin no differences were found for both experimental groups between spring and summer but values showed to be higher for the C group than in T group during summer. There were no differences in BCS nor in IP. The addition of urea to the mineral mix has deleterious effects upon the protein profile os suckling beef cows, when trere is high avalability of forage. The use of urea has no effect on reproduction performance

The interaction of lean and building information modeling in construction

Lean construction and Building Information Modeling are quite different initiatives, but both are having profound impacts on the construction industry. A rigorous analysis of the myriad specific interactions between them indicates that a synergy exists which, if properly understood in theoretical terms, can be exploited to improve construction processes beyond the degree to which it might be improved by application of either of these paradigms independently. Using a matrix that juxtaposes BIM functionalities with prescriptive lean construction principles, fifty-six interactions have been identified, all but four of which represent constructive interaction. Although evidence for the majority of these has been found, the matrix is not considered complete, but rather a framework for research to explore the degree of validity of the interactions. Construction executives, managers, designers and developers of IT systems for construction can also benefit from the framework as an aid to recognizing the potential synergies when planning their lean and BIM adoption strategies