How do scientists perceive the current publication culture? A qualitative focus group interview study among Dutch biomedical researchers.

OBJECTIVE: To investigate the biomedical scientist's perception of the prevailing publication culture. DESIGN: Qualitative focus group interview study. SETTING: Four university medical centres in the Netherlands. PARTICIPANTS: Three randomly selected groups of biomedical scientists (PhD, postdoctoral staff members and full professors). MAIN OUTCOME MEASURES: Main themes for discussion were selected by participants. RESULTS: Frequently perceived detrimental effects of contemporary publication culture were the strong focus on citation measures (like the Journal Impact Factor and the H-index), gift and ghost authorships and the order of authors, the peer review process, competition, the funding system and publication bias. These themes were generally associated with detrimental and undesirable effects on publication practices and on the validity of reported results. Furthermore, senior scientists tended to display a more cynical perception of the publication culture than their junior colleagues. However, even among the PhD students and the postdoctoral fellows, the sentiment was quite negative. Positive perceptions of specific features of contemporary scientific and publication culture were rare. CONCLUSIONS: Our findings suggest that the current publication culture leads to negative sentiments, counterproductive stress levels and, most importantly, to questionable research practices among junior and senior biomedical scientists

The impact of constructive operating lease capitalisation on key accounting ratios

Current UK lease accounting regulation does not require operating leases to be capitalised in the accounts of lessees, although this is likely to change with the publication of FRS 5. This study conducts a prospective analysis of the effects of such a change. The potential magnitude of the impact of lease capitalisation upon individual users' decisions, market valuations, company cash flows, and managers' behaviour can be indicated by the effect on key accounting ratios, which are employed in decision-making and in financial contracts. The capitalised value of operating leases is estimated using a method similar to that suggested by Imhoff, Lipe and Wright (1991), adapted for the UK accounting and tax environment, and developed to incorporate company-specific assumptions. Results for 1994 for a random sample of 300 listed UK companies show that, on average, the unrecorded long-term liability represented 39% of reported long-term debt, while the unrecorded asset represented 6% of total assets. Capitalisation had a significant impact (at the 1% level) on six of the nine selected ratios (profit margin, return on assets, asset turnover, and three measures of gearing). Moreover, the Spearman rank correlation between each ratio before and after capitalisation revealed that the ranking of companies changed markedly for gearing measures in particular. There were significant inter-industry variations, with the services sector experiencing the greatest impact. An analysis of the impact of capitalisation over the five-year period from 1990 to 1994 showed that capitalisation had the greatest impact during the trough of the recession. Results were shown to be robust with respect to key assumptions of the capitalisation method. These findings contribute to the assessment of the economic consequences of a policy change requiring operating lease capitalisation. Significant changes in the magnitude of key accounting ratios and a major shift in company performance rankings suggest that interested parties' decisions and company cash flows are likely to be affected

Chemical Modifications of Gold Surfaces with Basic Groups and a Fluorescent Nanoparticle Adhesion Assay To Determine Their Surface pKa

For pharmaceutical, biological, and biomedical applications, the functionalization of gold surfaces with pH-sensitive groups has great potential. The aim of this work was to modify gold surfaces with pH-sensitive groups and to determine the pKa of the modified gold surfaces using a fluorescent nanoparticle adhesion assay. To introduce pH-sensitive groups onto gold surfaces, we modified gold-coated silicon slides with four different bases: 4-mercaptopyridine (4-MP), 4-pyridylethylmercaptan (4-PEM), 4-aminothiophenol (4-ATP), and 2-mercaptoethylamine (2-MEA). To screen whether the modifications were successful, the binding of negatively charged fluorescently labeled nanoparticles to the positively charged surfaces was visualized by fluorescence microscopy and atomic force microscopy. Next, the pKa of the modified surfaces was determined by quantifying the pH-dependent adhesion of the fluorescently labeled nanoparticles with fluorescence spectroscopy. Fluorescence microscopy showed that the gold surfaces were successfully modified with the four different basic molecules. Moreover, fluorescence spectroscopy revealed that fluorescently labeled negatively charged nanoparticles bound onto gold surfaces that were modified with one of the four bases in a pH-dependent manner. By quantifying the adsorption of negatively charged fluorescently labeled nanoparticles onto the functionalized gold surfaces and using the Henderson–Hasselbalch equation, the pKa of these surfaces was determined to be 3.7 ± 0.1 (4-MP), 5.0 ± 0.1 (4-PEM), 5.4 ± 0.1 (4-ATP), and 7.4 ± 0.3 (2-MEA). We successfully functionalized gold surfaces with four different basic molecules, yielding modified surfaces with different pKa values, as determined with a fluorescent nanoparticle adhesion assay.Drug Delivery Technolog

Unconventional Transport Routes of Soluble and Membrane Proteins and Their Role in Developmental Biology

Many proteins and cargoes in eukaryotic cells are secreted through the conventional secretory pathway that brings proteins and membranes from the endoplasmic reticulum to the plasma membrane, passing through various cell compartments, and then the extracellular space. The recent identification of an increasing number of leaderless secreted proteins bypassing the Golgi apparatus unveiled the existence of alternative protein secretion pathways. Moreover, other unconventional routes for secretion of soluble or transmembrane proteins with initial endoplasmic reticulum localization were identified. Furthermore, other proteins normally functioning in conventional membrane traffic or in the biogenesis of unique plant/fungi organelles or in plasmodesmata transport seem to be involved in unconventional secretory pathways. These alternative pathways are functionally related to biotic stress and development, and are becoming more and more important in cell biology studies in yeast, mammalian cells and in plants. The city of Lecce hosted specialists working on mammals, plants and microorganisms for the inaugural meeting on "Unconventional Protein and Membrane Traffic" (UPMT) during 4-7 October 2016. The main aim of the meeting was to include the highest number of topics, summarized in this report, related to the unconventional transport routes of protein and membranes

Diphtheria toxoid and N-trimethyl chitosan layer-by-layer coated pH-sensitive microneedles induce potent immune responses upon dermal vaccination in mice

Dermal immunization using antigen-coated microneedle arrays is a promising vaccination strategy. However, reduction of microneedle sharpness and the available surface area for antigen coating is a limiting factor. To overcome these obstacles, a layer-by-layer coating approach can be applied onto pH-sensitive microneedles. Following this approach, pH-sensitive microneedle arrays (positively charged at coating pH 5.8 and nearly uncharged at pH 7.4) were alternatingly coated with negatively charged diphtheria toxoid (DT) and N-trimethyl chitosan (TMC), a cationic adjuvant. First, the optimal DT dose for intradermal immunization was determined in a dose-response study, which revealed that low-dose intradermal immunization was more efficient than subcutaneous immunization and that the EC50 dose of DT upon intradermal immunization is 3-fold lower, as compared to subcutaneous immunization. In a subsequent immunization study, microneedle arrays coated with an increasing number (2, 5, and 10) of DT/TMC bilayers resulted in step-wise increasing DT-specific immune responses. Dermal immunization with microneedle arrays coated with 10 bilayers of DT/TMC (corresponding with ± 0.6 μg DT delivered intradermally) resulted in similar DT-specific immune responses as subcutaneous immunization with 5 μg of DT adjuvanted with aluminum phosphate (8-fold dose reduction). Summarizing, the layer-by-layer coating approach onto pH-sensitive microneedles is a versatile method to precisely control the amount of coated and dermally-delivered antigen that is highly suitable for dermal immunization.</p

Accounting Restatements: Are they Always Bad News for Investors?

This study investigates a large sample of financial statement restatements over the period 1986-2001, and compares restatements caused by changes in accounting principles to those caused by errors. Typically, investors perceive restatements as negative signals due to three potential reasons: (i) the restatement indicates problems with the accounting system that may be manifestations of broader operational (and managerial) problems, (ii) the restatement causes downward revisions in future cash flows expectations, and (iii) the restatement indicates managerial attempts to cover up income decline through “cooking the books”. We provide evidence that market reactions to restatements due to errors are generally negative. We show that these restatements come in periods of declining profits and lower profits than industry peers for the restating firms, consistent with both opportunistic managerial behavior and operational problems. However, investors’ reactions to income-increasing restatements due to errors are not different from zero, suggesting that the perceived failure of the accounting system is just offset by the upward revisions in future cash flow expectations in these cases of income-increasing errors. Thus, our combined results show that not all restatements are alike; users of the information need to carefully assess the existence and potential effects of the three factors that typically cause the downward revisions in stock prices on a case by case basis

Reduction in PA28αβ activation in HD mouse brain correlates to increased mHTT aggregation in cell models

Huntington’s disease is an autosomal dominant heritable disorder caused by an expanded CAG trinucleotide repeat at the N-terminus of the Huntingtin (HTT) gene. Lowering the levels of soluble mutant HTT protein prior to aggregation through increased degradation by the proteasome would be a therapeutic strategy to prevent or delay the onset of disease. Native PAGE experiments in HdhQ150 mice and R6/2 mice showed that PA28αβ disassembles from the 20S proteasome during disease progression in the affected cortex, striatum and hippocampus but not in cerebellum and brainstem. Modulating PA28αβ activated proteasomes in various in vitro models showed that PA28αβ improved polyQ degradation, but decreased the turnover of mutant HTT. Silencing of PA28αβ in cells lead to an increase in mutant HTT aggregates, suggesting that PA28αβ is critical for overall proteostasis, but only indirectly affects mutant HTT aggregation

Culture as a mediator of climate change adaptation: Neither static nor unidirectional

Though there is increasing recognition of the cultural dimensions that shape climate change adaptation, our experience from working with actors engaged in adaptation policy and practice suggests that the role of culture still tends to be conceived in overly narrow and fixed terms. This is exemplified in portrayals of conservative cultural norms as stifling positive change. A growing body of research across the world indicates that the reality is seldom as simple as this – culture works in complex and variable ways, and, most importantly, is inherently dynamic. Drawing especially from research work on vulnerability and adaptation conducted in semi-arid regions, we illustrate this argument by briefly exploring three themes - multiple knowledge systems for farming in Botswana, the dynamics of pastoralist values and livelihoods in Kenya, and the interplay of caste and livelihood choices in India. Understanding how different facets of culture such as these operate in context helps move away from viewing culture statically as a barrier or enabler, and toward a more plural and dynamic appreciation of the role of culture in adaptation. This includes recognising the potential for factors that may be construed as barriers to become enablers. Critical, balanced engagement with cultural dimensions in both research and practice, understanding and working with these dynamic social structures, is essential if adaptation is to create meaningful and lasting change for those who need it most