To the Editor Condon, B. R.; Wyper, D. J.; Patterson, J. ...
Journal of cerebral blood flow and metabolism,
06/2016, Letnik:
6, Številka:
5
Journal Article
Setosphaeria turcica, a hemibiotrophic pathogenic dothideomycete, is the causal agent of Northern Leaf Blight of maize, which periodically causes significant yield losses worldwide. To explore ...molecular mechanisms of fungal pathogenicity and virulence to the host, an efficient targeted gene knockout transformation system using Agrobacterium tumefaciens was established with field collected strains. The starting materials, incubation time, induction medium type, Agrobacterium cell density, and method of co-incubation were optimized for deletion of 1,3,8-trihydroxynaphthalene reductase, a gene in the melanin biosynthesis pathway, as a test case. Four additional genes were deleted in two different S. turcica field isolates to confirm robustness of the method. One of these mutant strains was reduced in virulence compared with the wild-type strain when inoculated on susceptible maize. Transformation efficiency was ≈20 ± 3 transformants per 1× 10(6) germlings and homologous recombination efficiency was 33.3 to 100%.
This article analyzes several unresolved issues in World Trade Organization (WTO) law that may affect the WTO-consistency of measures that are likely to be taken to address climate change. How should ...the WTO deal with environmental subsidies under the General Agreement on Tariffs and Trade (GATT), the Agreement on Agriculture and the Subsidies and Countervailing Measures (SCM) Agreement? Can the general exceptions in GATT Article XX be applied to other agreements in Annex 1A? Are processing and production methods relevant to determining the issue of 'like products' in GATT Articles I and III, the SCM Agreement and the Antidumping Agreement and the TBT Agreement? What is the scope of paragraphs b and g in GATT Article XX and the relationship between these two paragraphs? What is the relationship between GATT Article XX and multilateral environmental agreements in the context of climate change? How should Article 2 of the TBT Agreement be interpreted and applied in the context of climate change? The article explores these issues.
This article describes how librarians can benefit from being members of research integrity committees. As two academic librarians, the authors share the ways that they have found professional ...fulfillment and joy through service on the Institutional Animal Care and Use Committee (IACUC) for vertebrate animal research activities and the Institutional Review Board (IRB) for human subjects research. Their participation on research integrity committees has provided opportunities to build new relationships, demonstrate their expertise, and find meaning in their contributions to research production. Participation on the IACUC has allowed one author to better understand research designs and instrumentation and laboratory techniques. She has built new relationships with research administrators, scientists, and lab managers, and found new opportunities to use her unique search skills. The other author, while serving on the IRB, has extended her professional network and highlighted her expertise as a qualitative researcher. She has built stronger relationships with research administrators and scholars and found new opportunities for advancing responsible data management conversations across campus. Participating in these committees has been professionally empowering and has allowed the authors to contribute to research integrity in important ways.
Research data services are provided by multiple units across and beyond the library, which is why communication and collaboration are paramount to building support for researchers. By exploring how ...Research Data Services (RDS) programs can function in the fragmented landscape of research support on campuses, we outline the role of collaboration in building programs. In this paper, we discuss building an RDS program by emphasizing three strategies for collaboration: collaborating within the library, collaborating across campus, and collaborating externally with those without direct ties to your organization. The aim of this paper is to offer attainable examples and strategies for building collaborations across campuses for libraries that have small or nascent RDS programs--how to approach and cultivate partnerships, how to set realistic goals, and how to work holistically within the fragmented academy. Keywords: research data services, external collaborations, cross-campus collaborations, goalsetting, outreach, faculty learning community, institutional support, open practices, affordability
Post-lumbar puncture (LP) headache may be due to "low CSF pressure", leading to stretching of pain sensitive intracranial structures. The low intracranial pressure is secondary to net loss of ...intracranial CSF. It has, however, not been possible to measure intracranial CSF volume accurately during life until recently. Intracranial CSF volume can now be measured non-invasively by a MRI technique. The changes in intracranial CSF volume were studied in 20 patients who had LP. Total intracranial CSF volume was reduced in 19 of the 20 patients 24 hours after LP (range -1.8 mls to -158.6 mls). Most of the CSF was lost from the cortical sulci. Very large reductions in intracranial CSF volume were frequently related to post-LP headache but some patients developed headache with relatively little alteration in the intracranial CSF volume. There was not a measurable change in position of the intracranial structures following LP.
Purpose
E6201 is a natural product–inspired novel inhibitor of mitogen-activated protein kinase/extracellular signal–regulated kinase kinase-1 (MEK1) and other kinases and is currently under ...development as an anticancer (parenteral administration) and antipsoriasis agent (topical application). In vitro and in vivo preclinical studies were performed to characterize the pharmacokinetics of E6201. Allometric scaling was applied to predict human pharmacokinetics of E6201.
Methods
In vitro metabolism studies for CYP induction and CYP inhibition were conducted using human hepatocytes and microsomes, respectively. Metabolic stability using microsomes and protein-binding studies using pooled plasma were performed for mice, rats, dogs, and human. Pharmacokinetics of E6201 and its isomeric metabolite, ER-813010, in mice, rats, and dogs was determined following single IV administration of E6201 at three dose levels. Bioanalysis was performed using LC/MS/MS. Pharmacokinetic parameters were determined using non-compartmental analysis, and allometric scaling with a two-compartment model was used to predict E6201 pharmacokinetics in humans.
Results
E6201 showed high plasma protein binding (>95%), and metabolic stability half-life ranged from 36 to 89 min across species. In vitro CYP inhibition (CYP1A2, 2C9, 2C19, 2D6, 2E1, and 3A) and CYP induction (CYP1A, 3A, 2C9, and 2C19) suggested no inhibitory or induction effect on the tested human CYPs up to 10 μM of E6201. Pharmacokinetics of E6201 in mice, rats, and dogs was characterized by mean clearance ranging from 3.45 to 10.92 L/h/kg, distribution volume ranging from 0.63 to 13.09 L/kg, and elimination half-life ranging from 0.4 to 1.6 h. ER-813010 was detected in all species with metabolite to parent exposure ratio (AUC
R
) ranging from 3.1 to 33.4% and exhibited fast elimination (<3 h). The allometry predicted high clearance and large volume of distribution of E6201 in humans and was in general in good agreement with the observed first human subject pharmacokinetics.
Conclusions
E6201 exhibited high clearance, high to moderate distribution, and fast elimination in preclinical species. In vitro results suggested that E6201 has low risk of drug–drug interactions due to CYP inhibition and induction in humans. In the first-in-man study, E6201 exhibited high clearance, which was well predicted by allometric scaling.
Experiments were carried out to investigate the effects of fluctuating low-level magnetic fields on the demography and behaviour of
Rhyzopertha dominica (F.). Adult insects were exposed to low-level ...magnetic fields, generated from both full- and half-wave rectified power supplies at 50
Hz and with magnetic-field strengths of 2–4 times that of the earth. Significant insect responses, in terms of changes to fecundity, development period and aspects of behaviour, were observed in many of the experiments and the nature of the response depended upon the power supply generating the magnetic field used.
There appeared to be a dose effect because the reduction in progeny production diminished with distance from the centre of the field and the effects upon fecundity were cumulative. Numbers of progeny produced declined steadily over a 5-week period of exposure to the magnetic field, contrasting with the control which increased over the same period. The behavioural experiments showed that, despite a marked position effect within the experimental room, the magnetic field clearly had a deterrent effect upon the insects.
The complex nature of the observed responses is discussed in relation to measured differences between the power supplies used in the experiments. The general issue of experimental methodology in such studies is also explored.
Objective – The University of New Hampshire (UNH) Library conducted an exploratory study of the pedagogical practices of social science instructors at UNH who teach using quantitative data in ...undergraduate courses. This study is connected to a suite of parallel studies at other higher education institutions that was designed and coordinated by Ithaka S+R.
The four aims of this study were to explore the ways in which instructors teach and engage undergraduates in the social sciences using quantitative data; understand the support needs of these instructors; develop actionable recommendations for campus stakeholders; and identify opportunities for the development of resources, services, or activities in the library to support the use of quantitative data in the classroom.
Methods – For the UNH study, the research team recruited eleven participants through convenience sampling for one-on-one, semi-structured interviews. The study sample included lecturers, assistant professors, associate professors, and full professors across seven social science disciplines from the Durham and Manchester campuses.
Results – Courses using data provide a unique opportunity for students to gain experience by working with hands-on examples. The two overarching themes identified speak to both the motivations of instructors who teach with data and the challenges and opportunities they face: teaching with data for data literacy and scientific literacy and teaching with data for statistical, data, and tools skill building.
Conclusion – Data literacy is an important set of competencies in part because of the quality and quantity of data students encounter; they need to have the ability to critically evaluate data, methods, and claims. This study directed attention to an area that had not previously been examined at UNH and is an important first step toward creating greater awareness and community of practice for social science instructors teaching with data. The UNH Library offers research data services and is exploring new ways of supporting data literacy. UNH has opportunities to create additional supports for instructors and students that could improve student learning outcomes. Such efforts may require cross-college or cross-department coordination as well as administrative support.
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