105,627 research outputs found
The contributions of interlocking loops and extensive nonlinearity to the properties of circadian clock models
No full textSensitivity and robustness are essential properties of circadian clock systems, enabling them to respond to the environment but resist noisy variations. These properties should be recapitulated in computational models of the circadian clock. Highly nonlinear kinetics and multiple loops are often incorporated into models to match experimental time-series data, but these also impact on model properties for clock models
A MAP of ye rout w'ch Hannibal took through GAUL & over the Alpes into ITALY
No full textPublished in volume 12 of "An Universal history, from the earliest account of time /
Compiled from original authors; and illustrated with maps, cuts, notes, &c. With a general index to the whole" in Chapter 6 The History of Rome, from the Beginning to the End of the second Punic War".The prime meridian was determined to be the Ferro meridian. Scale bar at the bottom of the map in Roman Miles
Consistent robustness analysis (CRA) identifies biologically relevant properties of regulatory network models
No full textA number of studies have previously demonstrated that "goodness of fit" is insufficient in reliably classifying the credibility of a biological model. Robustness and/or sensitivity analysis is commonly employed as a secondary method for evaluating the suitability of a particular model. The results of such analyses invariably depend on the particular parameter set tested, yet many parameter values for biological models are uncertain
Practice nurse involvement in giving depot neuroleptic injections: development of a patient assessment and monitoring checklist
No full textAround 25% of people with schizophrenia have no specialist contact, but are looked after entirely in general practice. We aimed to determine the involvement of practice nurses in administering depot neuroleptics, and their needs for training in patient assessment. Methods included a postal survey of all practice nurses in one health authority, and interviews with practice nurses and expert nurse advisers, to explore attitudes and knowledge. Of 140 practices, 93 employed 194 practice nurses between them. Of the 192 nurses who responded to the survey, 131 (68%) were currently administering depot neuroleptics, to a total of 278 patients between them. For many patients, the nurse was their only regular professional contact. Few nurses had any mental health training, and levels of knowledge of schizophrenia, its treatment and drug side-effects, were often no better than a lay person's. A one-day course was developed, attended by 21 practice nurses, at which written and videotaped educational material was provided and feedback on its usefulness obtained. The course participants welcomed training in a brief structured assessment of depot neuroleptic patients to be carried out every three months. This should enable them to detect changes in mental state and other care needs, and to bring them to the doctor's attention
Human Endothelial Cells Modulate CD4+ T Cell Populations and Enhance Regulatory T Cell Suppressive Capacity
No full textEndothelial cells (ECs) line the luminal surface of blood vessels and have an active role in the recruitment of leukocytes, including immune cell activation. Regulatory T cells (Tregs) are immune suppressor cells that maintain peripheral tolerance and must interact with the endothelium as they traffic into tissue. We hypothesized that human ECs could modulate Tregs and their suppressor function. Cocultures of CD4+ T cells with human umbilical vein ECs (HUVECs) or dermal microvascular ECs (HDMECs) were conducted and analyzed for activation and proliferation after 72 and 120 h using flow cytometry. In monocyte-depleted cultures, human ECs were found to support CD4+ T cell proliferation in the presence of external mitogens phytohemagglutinin or anti-CD3/28 antibodies (aCD3/28). Activation was shown by CD25 expression in these cells that also transiently expressed the Treg transcription factor FOXP3. HUVECs supported the specific concurrent proliferation of both effector T cells and Tregs when cocultured with aCD3/28. Purified Tregs were also functionally activated by prior coculture with EC to suppress effector T (Teff) cell proliferation. Both direct coculture and indirect coculture of EC and Treg showed activation of the Treg suppressive phenotype. However, whereas HUVEC showed enhancement of suppression by both mechanisms, HDMEC only supported Treg suppressive activity via the contact-independent mechanism. In the contact-independent cultures, the soluble mediators IL-6, GM-CSF, or G-CSF released from ECs following interferon-γ activation were not responsible for the enhanced Treg suppressor function. Following direct coculture, Treg expression of inhibitory receptors PD-1 and OX40 was elevated while activated EC expressed the counter ligands programmed death ligand (PD-L)1 and PD-L2. Therefore, human ECs have a role in supporting T cell proliferation and increasing Treg suppressor function. This ability of EC to enhance Treg function could offer novel targets to boost Treg activity during inflammatory disorders
Modelling the widespread effects of TOC1 signalling on the plant circadian clock and its outputs
No full textThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. This work was supported by the European Commission FP7 Collaborative Project TiMet (project 245143). SynthSys is a Centre for Integrative and Systems Biology supported by BBSRC and EPSRC award D019621. Work in P.M. laboratory is supported by grants from the Ramón Areces Foundation, from the Spanish Ministry of Science and Innovation (MICINN) (BIO2010-16483) and from EUROHORCS (European Heads Of Research Councils) and the European Science Foundation (ESF) through the EURYI Award.Peer reviewe
Letter, [Author unclear] to Paulina T. Merritt
No full textHandwritten letter to Paulina Merritt from an unknown author, October 1, 1876.
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