Miracle-dz/UniFAR-FTUs huggingface dataset:
Strategies for manipulating the relative concentration of recombinant rotavirus structural proteins during simultaneous production by insect cells.

Adequate production strategies of virus-like particles are among the challenges that must be addressed before such complex multimeric structures find practical applications as vaccines. Attainment of the correct stoichiometric relation between proteins that constitute virus-like particles should result in an increased productivity by maximizing the concentration of assembled proteins and preventing the accumulation of waste monomers. In this work, strategies for manipulating the relative concentration between two of the structural proteins that constitute rotavirus-like particles (VP2 and VP6) were explored using the insect cell baculovirus expression vector system. It was shown that multiplicity of infection is a useful tool for manipulating protein production rates and maximum concentrations in cultures expressing one or two recombinant proteins. Thus, multiplicity of infection can be employed for improving production of rotavirus-like particles. VP2 and VP6 production rates obtained during individual infections remained unchanged when both were simultaneously produced, indicating that such rates can be utilized for estimating protein concentrations during coexpression. Manipulation of the time of infection between the two recombinant baculoviruses, proposed here for the first time, also proved to be effective for controlling the relative protein concentrations. The use of such sequential infections constituted an effective production alternative that does not require high amounts of virus stocks and is easy to implement. In addition to VP2 and VP6, kinetic parameters for the individual production of the other two proteins (VP4 and VP7) that constitute rotavirus-like particles were also obtained.
Hours of Work and Fatigue-Related Error: A Survey of New Zealand Anaesthetists

A nationwide survey (70% response) documented anaesthetists’ hours of work, their perceptions about safety limits and their recollection of fatigue-related errors in clinical practice. In the preceding six months, 71% of trainees and 58% of specialists had exceeded their self-defined safety limits for continuous anaesthesia administration. For 50% of trainees and 27% of specialists, their average working week exceeded their own limits for maintaining patient safety, and for 63% of trainees and 40% of specialists, it exceeded their limits for maintaining their personal well-being. Fatigue-related errors were reported by 86% of respondents, with 32% recalling errors in the preceding six months. Specialists were more likely to report a fatigue-related error if they had exceeded their own safety limits for continuous anaesthesia administration, or for weekly work hours. Current measures are not preventing anaesthetists from working hours that they consider to be unsafe for patients or harmful to their own well-being.
Developing and evaluating complementary therapy services: part 2. Examining the effects of treatment on health status.

OBJECTIVES To investigate the effect on patient health status of an outpatient service providing acupuncture, osteopathy, and homeopathy. DESIGN Pragmatic quasiexperimental design with waiting-list control group. SETTING A district general hospital in the United Kingdom. SUBJECTS All patients referred to the service during the study period. OUTCOME MEASURES The Short Form 36-Item Health Status Survey (SF-36). RESULTS With the exception of the Physical Functioning scale, statistical differences in scores were found between the treatment and control group on all SF-36 scales. Sensitivity analysis designed to deal with nonresponse supports the robustness of the results. CONCLUSION This study provides evidence for the effectiveness of an outpatient acupuncture, osteopathy and homeopathy service in terms of benefits to patients' health status.
Chironomus tentans life‐cycle test: Design and evaluation for use in assessing toxicity of contaminated sediments

The development and standardization of toxicity test methods for assessing toxicity of contaminated freshwater sediments has focused predominantly on short‐term exposures and lethality. In many situations, however, toxicity is more likely to become manifest over long periods of time so there is need for standardized testing procedures by which sublethal sediment toxicity can be adequately assessed. In this study, we present and evaluate a new life cycle test, using the midge Chironomus tentans, which enables the assessment of sublethal toxicity of contaminated sediments. In designing the life cycle test, our goal was to make the assay relatively straightforward and, to the extent possible, methodologically compatible with the standard 10‐d test. The test is initiated with newly hatched (<24 h) larvae and uses four effects‐based endpoints to assess toxicity: survival, growth, emergence, and reproduction. Survival is determined at 20 d and at the end of the test by back‐calculating through emergence data. Growth can be determined at 20 d, which corresponds to the 10‐d endpoint in the 10‐d C. tentans growth test initiated with 10‐d‐old larvae. From day 23 to the end of the test, emergence and reproduction are monitored daily. The number of eggs per female is determined for each egg mass, which is then incubated for 6 d to determine hatching success. Each treatment in the life cycle test is terminated separately after 7 consecutive days without emergence. We evaluated the life cycle test by following one generation of C. tentans in sediments collected from the upper Mississippi River. Survival of larvae exceeded 90% at 20 d. Of these larvae, between 60 and 70% successfully emerged; survivorship among pupae and adults exceeded 85%. Mean egg production ranged from 906 to 1,107 eggs per female. The test required 65 d to complete, including pretest preparation. These data show that the C. tentans life cycle test can be used to assess sublethal toxicity accurately in contaminated sediments and provides a suitable compliment to the standard C. tentans 10‐d test.
Sustaining patient and public involvement in research: A case study of a research centre

The literature on patient and public involvement (PPI) in research covers a wide range of topics. However, one area of investigation that appears under developed is the sustainability and impact of PPI beyond involvement in time-limited research projects. This paper presents a case study of PPI development in one primary care research centre in England, and its approach to making this sustainable using documentary sources and material from a formal evaluation. We provide narrative accounts of the set-up, operation and main processes of PPI, and its perceived impact. PPI requires a long-term perspective with participation and trust growing over time, and both users and researchers learning what approaches work best. PPI is a complex interplay of clarity of purpose, defined roles and relationships, organised support (paid PPI staff) and a well-funded infrastructure. ‘Soft systems’ are equally important such as flexible and informal approaches to meetings, adapting timetables and environments to meet the needs of lay members and to create spaces for relationships to develop between researchers and lay members that are based on mutual trust and respect. This case study highlights that the right combination of ethos, flexible working practices, leadership, and secure funding goes a long way to embedding PPI beyond ad hoc involvement. This allows PPI in research to be integrated in the infrastructure and sustainable.
Epidemiological characteristics of fatal pedestrian accidents in Fars Province of Iran: a community-based survey.

OBJECTIVE To determine the epidemiological characteristics of fatal pedestrian accidents in Fars Province of Iran. METHODS This cross-sectional study was conducted in Fars Province of Iran during a 29-month period from March 2009 to July 2011. The data were from the Fars Forensic Medicine Registry. In 4 923 recorded road traffic accident fatalities, 971 deaths were due to pedestrian accidents. The demographic and accident-related information were analyzed by SPSS version 11.5. P value less than 0.05 was considered significant. RESULTS The mean age of decedents was (47.2+/-26.2) years, ranging from 6 months to 103 years old. Males accounted for 69.8% of all deaths. Fatal accidents were most common in September; 56.1% of the fatal injuries occurred on intracity roads and 33.1% on extracity roads. Fatal head injuries were present in 60.54% of cases. Evaluation of the injury site and the cause of death found that they were significantly associated with age, interval between injury and death. Besides, the type of roads played an important role in mortality. CONCLUSION Although the clinical management of trauma patients has been improved in our country in the recent decade, decreasing the burden of injuries needs coordination among trauma system organizations.
Is there a cognate advantage for typically developing Spanish-speaking English-language learners?

PURPOSE Cross-linguistic cognates are words that share form and meaning in two languages (e.g., helicopter-helicóptero); translation equivalents are words that share meaning but not form (e.g., house-casa). Research consistently demonstrates a performance speed and/or accuracy advantage for processing cognates versus noncognates in bilingual adults; studies with children are limited, with equivocal results. We investigated the potential for a cognate advantage for processing expressive and receptive vocabulary in the spoken (vs. written) modality in typically developing Spanish-speaking English-language learners (ELLs). METHOD Thirty 8- to 13-year-old native Spanish-speaking children learning English as their second language completed standardized vocabulary tests in spoken English. Each test item was classified as a cognate or noncognate based on phonological overlap with its Spanish translation. Group and individual analyses were used to examine the effects of cognates. RESULTS At the group level, children's test scores were higher for items that were classified as cognates as compared to noncognates of comparable difficulty. However, not all children demonstrated this cognate advantage. Age predicted significant amounts of variance in cognate performance on the receptive test. CONCLUSION Overall, typically developing Spanish-speaking school-age ELL students demonstrated a cognate advantage. There was also considerable within-group variation in performance. Clinical implications are discussed, and directions for future study are provided.
City Size and Wage Disparity in Segmented Labour Market in China

type="main"> The relation between city size and wage inequality is well established for Western countries. This paper finds that city size–wage premium exists across Chinese cities to a lower extent than the Western world. Further, using a simplified model on the Chinese Household Income Project survey data, we find that the city size–wage premium varies with difference in skills among urban citizens. The variation amounts to 50% more for the high-skill workers compared with their low-skill counterparts. Moreover, owing to the presence of segmented labour market, the patterns of city size–wage premium and city size–wage inequality premium are notably different for the migrants, who receive a much lesser wage than the citizens and do not experience wage variation owing to their skill heterogeneity.
House dust mites induce proliferation of severe asthmatic smooth muscle cells via an epithelium-dependent pathway.

RATIONALE Asthma is a frequent airway disease, and asthma control determinants have been associated with indoor allergen sensitization. The most frequent allergens are house dust mites (HDM), which act in vivo on the bronchial epithelial layer. Severe asthma has also been associated with bronchial remodeling and more specifically with increased mass of bronchial smooth muscle (BSM). However, the relationship between HDM stimulation of the bronchial epithelial layer and BSM remodeling is unknown. OBJECTIVES To evaluate whether epithelial stimulation with HDM induces BSM cell proliferation in subjects with severe asthma. METHODS A total of 22 subjects with severe asthma and 27 subjects with no asthma were recruited. We have developed an in vitro culture model combining an epithelium layer in air-liquid interface (ALI) interacting with BSM. We assessed BSM proliferation using BrdU incorporation. We explored the role of epithelium-derived mediators using reverse-transcriptase polymerase chain reaction (RT-PCR) and ELISA in vitro and in vivo. Finally, leukotrienes receptor expression was assessed in vitro by flow cytometry and RT-PCR and ex vivo by laser microdissection and RT-PCR. MEASUREMENTS AND MAIN RESULTS We found that epithelial stimulation by HDM selectively increased the proliferation of asthmatic BSM cells and not that of nonasthmatic cells. The mechanism involved epithelial protease-activated receptor-2-dependent production of leukotrienes C4 associated with an overexpression of leukotrienes receptor CysLTR1 by asthmatic BSM cells in vitro and ex vivo. CONCLUSIONS This work demonstrates the selective role of HDM on BSM remodeling in patients with severe asthma and points out different therapeutic targets at epithelial and smooth muscle levels.
Educational Mobility Across Three Generations of American Women

We analyze the intergenerational transmission of education in a three-generation sample of women from the 20th century US. We find strong three-generation educational persistence, with the association between the education of grandmothers and their granddaughters approximately two times stronger than would be expected under the type of first-order autoregressive transmission structure that has been assumed in much of the existing two-generation mobility literature. These findings are robust to using alternative empirical specifications and sample constructions, and are successfully replicated in a second independently drawn data set. Analyses that include males in the youngest and oldest generations produce very similar estimates. A variety of potential mechanisms linking the educational outcomes of grandparents and grandchildren are discussed and where possible tested empirically.
Relative sparing of item recognition memory in a patient with adult‐onset damage limited to the hippocampus

There is disagreement about whether selective hippocampal lesions in humans cause clear item recognition as well as recall deficits. Whereas Reed and Squire (Behav Neurosci 1997;111:667–775) found that patients with adult‐onset relatively selective hippocampal lesions showed clear item recognition deficits, Vargha‐Khadem et al. (Science 1997;277:376–380, Soc Neurosci Abstr 1998;24:1523) found that 3 patients who suffered selective hippocampal damage in early childhood showed clear recall deficits, but had relatively normal item recognition. Manns and Squire (Hippocampus 1999;9:495–499) argued, however, that item recognition may have been spared in these patients because the early onset of their pathology allowed compensatory mechanisms to develop. Therefore, to determine whether early lesion onset is critical for the relative sparing of item recognition and to determine whether its occurrence is influenced by task factors, we extensively examined item recognition in patient Y.R. , who has pathology of adult‐onset restricted to the hippocampus. Like the developmental cases, she showed clear free recall deficits on 34 tests, but her item recognition on 43 tests was relatively spared, and markedly less disrupted than her recall. Her item recognition performance relative to that of her controls was not significantly influenced by whether tests tapped visual or verbal materials, had a yes/no or forced‐choice format, contained few or many items, had one or several foils per target item, used short or very long delays, or were difficult or easy for normal subjects. Interestingly, YR's bilateral hippocampal destruction was greater than at least 2 of the 3 patients of Manns and Squire (Hippocampus 1999;9:495–499). The possible reasons why item recognition differs across patients with relatively selective hippocampal damage of adult‐onset and how the reasons that are truly critical can be best identified are discussed. Hippocampus 2002;12:325–340. © 2002 Wiley‐Liss, Inc.
Roles for librarians in systematic reviews: a scoping review

Objective What roles do librarians and information professionals play in conducting systematic reviews? Librarians are increasingly called upon to be involved in systematic reviews, but no study has considered all the roles librarians can perform. This inventory of existing and emerging roles aids in defining librarians’ systematic reviews services. Methods For this scoping review, the authors conducted controlled vocabulary and text-word searches in the PubMed; Library, Information Science & Technology Abstracts; and CINAHL databases. We separately searched for articles published in the Journal of the European Association for Health Information and Libraries, Evidence Based Library and Information Practice, the Journal of the Canadian Heath Libraries Association, and Hypothesis. We also text-word searched Medical Library Association annual meeting poster and paper abstracts. Results We identified 18 different roles filled by librarians and other information professionals in conducting systematic reviews from 310 different articles, book chapters, and presented papers and posters. Some roles were well known such as searching, source selection, and teaching. Other less documented roles included planning, question formulation, and peer review. We summarize these different roles and provide an accompanying bibliography of references for in-depth descriptions of these roles. Conclusion Librarians play central roles in systematic review teams, including roles that go beyond searching. This scoping review should encourage librarians who are fulfilling roles that are not captured here to document their roles in journal articles and poster and paper presentations.
Inhibition of DNA synthesis by aphidicolin induces supercoiling in simian virus 40 replicative intermediates.

Highly torsionally stressed replicative intermediate SV40 DNA molecules are produced when ongoing replicative DNA synthesis is inhibited by aphidicolin, a specific inhibitor of DNA polymerase alpha. The high negative superhelical density of these molecules can be partially released by intercalating drugs such as chloroquine or ethidium bromide. The torsionally stressed replicative intermediates bind to monoclonal anti‐Z‐DNA antibodies. Electron microscopy of anti‐Z‐DNA cross‐linked to torsionally stressed replicative intermediates shows that the antibody specifically binds close to the replication forks. The superhelical structures are not formed when SV40 DNA replication is inhibited by both aphidicolin and novobiocin, suggesting that a topoisomerase type II‐like enzyme is somehow involved in the introduction of torsional strain in replicative intermediate DNA. One interpretation of our data is that fork movement continues to some rather limited extent when SV40 DNA synthesis in replicative chromatin is blocked by aphidicolin. After deproteinization, the exposed single‐stranded DNA branches reassociate to form paranemic DNA structures with left‐handed helical stretches, while the reduced linking number of the parental strands induces a high negative superhelical density.
Activation of HER Family Signaling as a Mechanism of Acquired Resistance to ALK Inhibitors in EML4-ALK–Positive Non–Small Cell Lung Cancer

Purpose: Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKI) such as crizotinib show marked efficacy in patients with non–small cell lung cancer positive for the echinoderm microtubule-associated protein–like 4 (EML4)–ALK fusion protein. However, acquired resistance to these agents has already been described in treated patients, and the mechanisms of such resistance remain largely unknown. Experimental Design: We established lines of EML4-ALK–positive H3122 lung cancer cells that are resistant to the ALK inhibitor TAE684 (H3122/TR cells) and investigated their resistance mechanism with the use of immunoblot analysis, ELISA, reverse transcription and real-time PCR analysis, and an annexin V binding assay. We isolated EML4-ALK–positive lung cancer cells (K-3) from a patient who developed resistance to crizotinib and investigated their characteristics. Results: The expression of EML4-ALK was reduced at the transcriptional level, whereas phosphorylation of epidermal growth factor receptor (EGFR), HER2, and HER3 was upregulated, in H3122/TR cells compared with those in H3122 cells. This activation of HER family proteins was accompanied by increased secretion of EGF. Treatment with an EGFR-TKI induced apoptosis in H3122/TR cells, but not in H3122 cells. The TAE684-induced inhibition of extracellular signal–regulated kinase (ERK) and STAT3 phosphorylation observed in parental cells was prevented by exposure of these cells to exogenous EGF, resulting in a reduced sensitivity of cell growth to TAE684. K-3 cells also manifested HER family activation accompanied by increased EGF secretion. Conclusions: EGF-mediated activation of HER family signaling is associated with ALK-TKI resistance in lung cancer positive for EML4-ALK. Clin Cancer Res; 18(22); 6219–26. ©2012 AACR.
Location, Location, Location: Repetition and Proximity Increase Advertising Effectiveness

We examine a large-scale field experiment that measures the effect of online display advertising. Yahoo! Research and an American apparel retailer collaborated on the experiment that tracked the online and offline sales of 3 million retailer customers. We measure the impact of the frequency of advertising exposure using a simple randomized experiment: users in the ‘Full’ treatment group see the retailer’s ads, users in the ‘Control’ group see unrelated control ads, and users in the ‘Half’ treatment group see an equal probability mixture of the retailer and control ads. We find strong benefits to repeated exposures among users who see up to 50 ads, with revenues increasing approximately linearly at a rate of 4¢ per exposure. We find especially high ad effectiveness for the retailer’s best customers and those who live closest to its brick-and-mortar locations; these findings are consistent with advertising in a Hotelling model of differentiated firms.
Should I Stay or Should I Go: The Impact of Public Duty Motivation on Turnover Intentions

Despite the expansion of public service motivation (PSM) research in recent years, only a few studies have linked PSM with public employees` turnover, and they have typically understood turnover as a dichotomous decision of staying versus leaving. Unlike previous research, we explore the relationship by taking into account various exit options. Utilizing data from the 2005 Merit Principles Survey, we classify public employees` exit strategies into four types-not leaving, retiring, moving to another federal agency, and resigning from federal service-and examine how an indirect measure of PSM influences which of these exit strategies they intend to follow. We employ the indirect measure due to data availability; following previous research, we name this measure public duty motivation. Our findings suggest that the impact of public duty motivation varies across intended exit strategies: it decreases the likelihood of public employees intending to retire, while it leads them to be more likely to intend to move to another job within the federal government. In contrast, it is not a significant predictor of public employees` intention to resign from federal service.