172,141 research outputs found
Upper limits on the 21 cm power spectrum atz = 5.9 from quasar absorption line spectroscopy
No full textWe present upper limits on the 21 cm power spectrum at z = 5.9 calculated from the model-independent limit on the neutral fraction of the intergalactic medium of derived from dark pixel statistics of quasar absorption spectra. Using 21CMMC, a Markov chain Monte Carlo Epoch of Reionization analysis code, we explore the probability distribution of 21 cm power spectra consistent with this constraint on the neutral fraction. We present 99 per cent confidence upper limits of Δ2(k) < 10–20 mK2 over a range of k from 0.5 to 2.0 h Mpc−1, with the exact limit dependent on the sampled k mode. This limit can be used as a null test for 21 cm experiments: a detection of power at z = 5.9 in excess of this value is highly suggestive of residual foreground contamination or other systematic errors affecting the analysis
ON-LINE CHARACTERIZATION OF CHOLINESTERASE INHIBITORS BY IMMOBILIZED ENZYME REACTORS
No full textIn the search for new therapeutics for Alzheimer’s Disease (AD), the investigation of the mechanism of action of new cholinesterase inhibitors represents a key aspect for new lead selection and subsequent optimization and development. However, the in vitro characterization of drug candidates on isolated target enzymes often requires a long operating time and a large amount of disposable expensive material. The recent development and aplication of stable immobilized enzyme reactors (IMERs) can ameliorate these concerns, and such in-solution methods should be potentially utilized in automated procedures to obtain efficient and effective higher throughput screening. In this context, the focus of this work was the development and characterization of a new IMER containing immobilized human recombinant butyrylcholinesterase (BChE) for the on-line kinetic characterization of specific, pseudo-irreversible and brain-targeted BChE inhibitors as potential drug candidates for AD. The selected phenserine and cymserine analogues were synthesized, characterized by classical ex vivo binding assays [1], and assessed by BChE-IMER.
For a pseudo-irreversible inhibitor, the kinetics constants describe the mode and duration of enzyme inhibition that will, in turn, influence the duration of the inhibitors’s in vivo pharmacological actions. The kinetic constants were determined for selected phenserine and cymserine analogues using a purposely-designed on-line procedure. Specifically, agents were inserted on to the BChE-IMER that fed directly into a HPLC system connected to a UV-Vis detector, BChE-IMER activity was determined on the basis of the Ellman reaction [2]. The carbamoylation and decarbamoylation phases at different inhibitor concentrations were then monitored continuously over time. Results allowed elucidation of the inhibition duration, mode of action and structure-activity relationships of the inhibitors of interest, which were compared to available values deriving from classical assessment.
(1) N.H. Greig, T. Utsuki, D.K. Ingram, Y. Wang, G. Pepeu, C. Scali, Q.S. Yu, I. Mamczarz, H.W. Holloway, T. Giordano, D. Chen, K. Furukawa, K. Sambamurti, A. Brossi, D.K. Lahiri: Selective butyrylcholinesterase inhibition elevates brain acetylcholine, augments learning and lowers Alzheimer beta-amyloid peptide in rodent. Proc Natl Acad Sci USA 2005, 102: 17213-18.
(2) G.L. Ellman, K.D. Courtney, V. Jr. Andres, R.M. Featherstone. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 1961, 7: 88-95
Constraints on the temperature of the intergalactic medium atz= 8.4 with 21-cm observations
No full text
Autistic symptoms in Greig cephalopolysyndactyly syndrome: a family case report
No full textAbstract Background Greig cephalopolysyndactyly syndrome is a rare multiple congenital anomaly syndrome characterized by the triad of polysyndactyly (preaxial or mixed preaxial and postaxial), macrocephaly, and ocular hypertelorism. Little is known about the neuropsychological phenotype and the developmental features of this syndrome. Case presentation We describe the clinical features of a 7-year-old Italian white boy affected by Greig cephalopolysyndactyly syndrome in comorbidity with autism spectrum disorder and the case of his 45-year-old white father, carrying the same point deletion (c.3677del) in the GLI3 gene and showing subclinical autistic symptoms. We performed a neuropsychiatric assessment of cognitive, adaptive, socio-communicative, and behavioral skills of the child. Concurrently, the father underwent his first psychiatric evaluation of cognitive skills and autistic symptoms. Conclusions We report the first clinical description of an association between autistic symptoms and Greig cephalopolysyndactyly syndrome in two members of the same family with the same genetic point deletion. Further research is required in order to draw an accurate conclusion regarding the association between Greig cephalopolysyndactyly syndrome and autism
More c-Bhaskar Rao designs with small block size
No full textAbstractIn this article we resolve some of the open problems left in two other articles. A c-Bhaskar Rao design, i.e., a c-BRD(v,k,λ), is formed by signing the v by b incidence matrix of a BIBD(v,k,λ) so that the inner product of any two distinct rows is c. We complete Greig, Hurd, McCranie and Sarvate's work on the spectrum of c-BRD(v,4,λ) when c≠0. In the classic (i.e., c=0) case, we establish the existence of 0-BRD(3t+1,4,2) for all 3t+1⩾433, with at most 30 smaller exceptions, all with t odd. Morgan, Preece and Rees have given a list of nested BIBDs with v⩽16 and r⩽30; they have one open case. By reformulating this problem, and constructing a (−1)-BRD(16,10,9), we provide a solution for this open case
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Alternative job search strategies in remote rural and peri-urban labour markets: the role of social networks
No full textThis paper examines the importance of informal methods (especially social networking) to the job search strategies used by unemployed people. It compares three areas: a small rural town; a larger, more sparsely populated, remote rural area; and a centrally-located, peri-urban labour market. The analysis is based first on survey research undertaken with 490 job seekers across the study areas. Emerging issues were then followed up during a series of twelve focus groups. The survey research showed that job seekers in the rural study areas were significantly more likely to use social networks to look for work. However, those who had experienced repeated or long-term periods out of work, the unskilled and young people were significantly less likely to use such networks. Focus groups confirmed the perceived importance of social networking to the job search process in rural areas, in contrast to the more marginal role such methods appear to play in peri-urban settings. For many rural job seekers, formal job search activities conducted through Jobcentres were seen as largely symbolic, lacking the practical value of social networking. These results suggest that service providers seeking to assist unemployed people in rural areas need to address the problems faced by many disadvantaged job seekers who are currently caught between their lack of social network relations and the absence of local public employment service facilities in more remote communities
Mitomycin C in highly myopic eyes - Author reply
No full textOphthalmology. 2005 Feb;112(2):208-18; discussion 219.
Mitomycin C modulation of corneal wound healing after photorefractive keratectomy in highly myopic eyes.
Gambato C, Ghirlando A, Moretto E, Busato F, Midena E.
SourceRefractive Surgery Service and Antimetabolite Therapy Research Unit, Department of Ophthalmology, University of Padova, Padova, Italy.
Abstract
PURPOSE: To evaluate the role of topical mitomycin C in corneal wound healing (CWH) after photorefractive keratectomy (PRK) in highly myopic eyes.
DESIGN: Prospective, double-masked, randomized clinical trial.
PARTICIPANTS: Seventy-two eyes of 36 patients affected by high (>7 diopters) myopia.
METHODS: In each patient, one eye was randomly assigned to PRK with intraoperative topical 0.02% mitomycin C application, and the fellow eye was treated with a placebo. Postoperatively, mitomycin C-treated eyes received artificial tears (3 times daily, tapered in 3 months), whereas the fellow eye was treated with fluorometholone sodium 2% and artificial tears (3 times daily, tapered in 3 months).
MAIN OUTCOME MEASURES: Uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA), contrast sensitivity, manifest refraction, and biomicroscopy. Contrast sensitivity was determined using the Pelli-Robson chart. Corneal confocal microscopy documented CWH.
RESULTS: Mean follow-up was 18 months (range, 12-36). No side effects or toxic effects were documented. At 12-month follow-up examination, UCVAs (logarithm of the minimum angle of resolution) were 0.4+/-0.48 and 0.5+/-0.53 (P = .03) in mitomycin C-treated eyes and corticosteroid-treated eyes, respectively. At 1 year, corneal haze developed in 20% of corticosteroid-treated eyes, versus 0% of mitomycin C-treated eyes. At 12, 24, and 36 months, corneal confocal microscopy showed activated keratocytes and extracellular matrix significantly more evident in untreated eyes (Ps = 0.004, 0.024, and 0.046, respectively).
CONCLUSION: Topical intraoperative application of 0.02% mitomycin C can reduce haze formation in highly myopic eyes undergoing PRK.
Comment in
Ophthalmology. 2006 Feb;113(2):357; author reply 357-8
- …
