bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of cancer‐related potential biomarkers based on lncRNA–pseudogene–mRNA competitive networks
Authors: Wu Cheng , Wei Yunzhen , Zhu Yinling , Li Kun , Zhu Yanjiao , Zhao Yichuan , Chang Zhiqiang , Xu Yan
Published: February 2018

Accumulating evidence indicates that mRNAs and noncoding RNAs act as competitive endogenous RNAs (ceRNAs) and play a key role in tumorigenesis. However, the complex competitive relationship among genes remains unknown. In the present study, the long noncoding RNAs (lncRNAs), pseudogenes and mRNAs that compete with common microRNAs are defined as lncRNA–pseudogene–mRNA competitive triples. We find that some candidate ceRNAs, modules and triples are associated with cancers and can significantly divide patients into high‐risk and low‐risk groups; thus, they may serve as potential cancer biomarkers. In sum, the present study systematically analyzes the association between competitive triples and cancer, which provides a reference for a deeper understanding of cancer progression.
Entangled signal pathways can both control expression stability and induce stochastic focusing
Authors: Wang Haohua , Liu Peijiang , Li Qingqing , Zhou Tianshou
Published: February 2018

Gene transcription is often controlled by multiple interacting signal pathways, but how these pathways impact gene expression is not fully understood. Here, we refine a mechanic model based on experiments in murine embryonic stem cells and analyze the influence of pathway–pathway cross‐talk strength (CTS) on mRNA expression stability. We find that the CTS can tune this stability, depending on the manner of regulation. Furthermore, there is an optimal CTS such that the expression pattern is most stable but free energy consumption is at its highest; the CTS can induce stochastic focusing of the mRNA level but this is at the cost of energy. In both cases, there is a cross–talk‐mediated trade‐off, implying that entangled signal pathways can control both expression stability and energy dissipation.
Mitochondrial dysfunction and axon degeneration in progressive multiple sclerosis
Authors: Campbell Graham , Mahad Don J.
Published: February 2018

The neuron is the target of inflammatory demyelinating processes in multiple sclerosis (MS). In progressive MS, however, there is a gathering body of evidence indicating that molecular changes converge on mitochondria within neuronal cell bodies. The most reproducible change relates to mitochondrial respiratory chain complex deficiency, which compromises the capacity of neurons to generate ATP. The resulting energy failure state is coupled with an increase in demand for energy by the demyelinated axon, being particularly relevant to the long tracts such as corticospinal tracts with long projection axons. Recent work in our laboratory and that of our collaborators indicates the limited reflection of the mitochondria changes within neurons in experimental disease models. The mitochondrial changes within neuronal compartments are likely to offer novel targets for the improvement in neuronal function in patients with progressive MS.
CQ sensitizes human pancreatic cancer cells to gemcitabine through the lysosomal apoptotic pathway via reactive oxygen species
Authors: Fu Zhiping , Cheng Xi , Kuang Jie , Feng Haoran , Chen Lingxie , Liang Juyong , Shen Xiaonan , Yuen Stanley , Peng Chenghong , Shen Baiyong , Jin Zhijian , Qiu Weihua
Published: February 2018

As an established anticancer drug, gemcitabine (GEM) is an effective systemic treatment for advanced pancreatic cancer (PC). However, little is known about the potential effectors that may modify tumour cell sensitivity towards GEM. Autophagy, as a physiological cellular mechanism, is involved in both cell survival and cell death. In this study, we found that exposure to GEM induced a significant increase in autophagy in a dose‐dependent manner in PANC‐1 and BxPC‐3 cells. Inhibition of autophagy by chloroquine (CQ) and ATG7 siRNA increased GEM‐induced cytotoxicity, and CQ was more effective than ATG7 siRNA. Moreover, CQ significantly enhanced GEM‐induced apoptosis, while ATG7 siRNA failed to show the similar effect. Subsequently, we identified a potential mechanism of this cooperative interaction by showing that GEM with CQ pretreatment markedly triggered reactive oxygen species (ROS) boost and then increased lysosomal membrane permeability. Consequently, cathepsins released from lysosome into the cytoplasm induced apoptosis. We showed that CQ could enhance PC cells response to GEM in xenograft models. In conclusion, our data showed that CQ sensitized PC cells to GEM through the lysosomal apoptotic pathway via ROS. Thus, CQ as a potential adjuvant to GEM might represent an attractive therapeutic strategy for PC treatment.
Atmospheric DMS in the Arctic Ocean and Its Relation to Phytoplankton Biomass
Authors: Park Ki‐Tae , Lee Kitack , Kim Tae‐Wook , Yoon Young Jun , Jang Eun‐Ho , Jang Sehyun , Lee Bang‐Yong , Hermansen Ove
Published: February 2018

We recorded and analyzed the atmospheric dimethyl sulfide (DMS) mixing ratios at a remote Arctic location (Svalbard; 78.5°N, 11.8°E) during phytoplankton bloom periods in the years 2010, 2014, and 2015 and found varying regional relationships between the atmospheric DMS and the extent of exposure of the air mass to the phytoplankton biomass in the ocean surrounding the observation site. The DMS production capacity of the Greenland Sea was estimated to be a factor of 3 greater than that of the Barents Sea, whereas the phytoplankton biomass in the Barents Sea was more than twofold than that in the Greenland Sea. These apparently contradictory results may be induced by the occurrence of a greater abundance of DMS‐producing phytoplankton in the Greenland Sea than in the Barents Sea during the phytoplankton bloom periods.
The Slip Behavior and Source Parameters for Spontaneous Slip Events on Rough Faults Subjected to Slow Tectonic Loading
Authors: Tal Yuval , Hager Bradford H.
Published: February 2018

We study the response to slow tectonic loading of rough faults governed by velocity weakening rate and state friction, using a 2‐D plane strain model. Our numerical approach accounts for all stages in the seismic cycle, and in each simulation we model a sequence of two earthquakes or more. We focus on the global behavior of the faults and find that as the roughness amplitude, br, increases and the minimum wavelength of roughness decreases, there is a transition from seismic slip to aseismic slip, in which the load on the fault is released by more slip events but with lower slip rate, lower seismic moment per unit length, M0,1d, and lower average static stress drop on the fault, Δτt. Even larger decreases with roughness are observed when these source parameters are estimated only for the dynamic stage of the rupture. For br ≤ 0.002, the source parameters M0,1d and Δτt decrease mutually and the relationship between Δτt and the average fault strain is similar to that of a smooth fault. For faults with larger values of br that are completely ruptured during the slip events, the average fault strain generally decreases more rapidly with roughness than Δτt.
Crystal structures of FMN‐bound and FMN‐free forms of dihydroorotate dehydrogenase from Trypanosoma brucei
Authors: Kubota Tomomi , Tani Osamu , Yamaguchi Tomohiko , Namatame Ichiji , Sakashita Hitoshi , Furukawa Koji , Yamasaki Kazuhiko
Published: February 2018

Dihydroorotate dehydrogenase (DHODH) is a flavin‐binding enzyme essential for pyrimidine biosynthesis, which converts dihydroorotate to orotate. Three‐dimensional structures of cytosolic DHODH of parasitic protozoa are of interest in drug discovery for neglected tropical diseases, especially because these enzymes possess significantly different structural and functional properties from the membrane‐associated human enzyme. The existing crystal structures of the flavin mononucleotide (FMN)‐bound DHODHs reveal a number of interactions stabilizing FMN. However, to understand the binding mechanism correctly, it is necessary to compare the structures of the FMN‐bound and FMN‐free forms, because the protein moiety of the former is not necessarily the same as the latter. Here, we prepared the FMN‐free DHODH of Trypanosoma brucei using an Escherichia coli overexpression system. Although this apoform lacks enzymatic activity, simple incubation with FMN activated the enzyme. It was stable enough to be crystallized, enabling us to determine its structure by X‐ray crystallography at 1.6 Å resolution. We also determined the FMN‐bound form at 1.8 Å resolution. Although the two structures have essentially the same scaffold, we observed flipping of a peptide‐bond plane in the vicinity of the FMN‐binding site, accompanied by an alternative hydrogen‐bonding pattern. Comparisons of B factors of the protein main chain revealed that binding of FMN decreased flexibility of most of the residues at the FMN‐binding site, but increased flexibility of a lid‐like loop structure over the active center. This increase was ascribed to a conformational change in an FMN‐contacting residue, Asn195, which induced a rearrangement of a hydrogen‐bond network of the residues comprising the lid.
Chemoenzymatic Approaches to the Synthesis of the Calcimimetic Agent Cinacalcet Employing Transaminases and Ketoreductases
Authors: Marx Lisa , Ríos‐Lombardía Nicolás , Farnberger Judith F. , Kroutil Wolfgang , Benítez‐Mateos Ana I. , López‐Gallego Fernando , Morís Francisco , González‐Sabín Javier , Berglund Per
Published: February 2018

Several chemoenzymatic routes have been explored for the preparation of cinacalcet, a calcimimetic agent. Transaminases (TAs) and ketoreductases (KREDs) turned out to be useful biocatalysts for the preparation of key optically active precursors. Thus, the asymmetric amination of 1‐acetonaphthone yielded an enantiopure (R)‐amine, which can be alkylated in one step to yield cinacalcet. Alternatively, the bioreduction of the same ketone resulted in an enantiopure (S)‐alcohol, which was easily converted into the previous (R)‐amine. In addition, the reduction was efficiently performed with the KRED and its cofactor co‐immobilized on the same porous surface. This self‐sufficient heterogeneous biocatalyst presented an accumulated total turnover number (TTN) for the cofactor of 675 after 5 consecutive operational cycles. Finally, in a preparative scale synthesis the TA‐based approach was performed in aqueous medium and led to enantiopure cinacalcet in two steps and 50% overall yield.

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Aniline ortho C−H Sulfuration/Cyclization with Elemental Sulfur for Efficient Synthesis of 2‐Substituted Benzothiazoles under Metal‐Free Conditions
Authors: Jiang Jingjing , Li Guozheng , Zhang Feng , Xie Hao , Deng Guo‐Jun
Published: February 2018

A three‐component synthesis of 2‐substituted benzothiazoles from aryl amines, elemental sulfur and styrenes or aryl acetylenes in 1‐methylpyrrolidin‐2‐one (NMP) is described. Two C−S and one C−N bonds were selectively formed in one‐pot under metal‐free conditions.

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N‐Heterocyclic‐Carbene‐Treated Gold Surfaces in Pentacene Organic Field‐Effect Transistors: Improved Stability and Contact at the Interface
Authors: Lv Aifeng , Freitag Matthias , Chepiga Kathryn M. , Schäfer Andreas H. , Glorius Frank , Chi Lifeng
Published: February 2018

N‐Heterocyclic carbenes (NHCs), which react with the surface of Au electrodes, have been successfully applied in pentacene transistors. With the application of NHCs, the charge‐carrier mobility of pentacene transistors increased by five times, while the contact resistance at the pentacene–Au interface was reduced by 85 %. Even after annealing the NHC–Au electrodes at 200 °C for 2 h before pentacene deposition, the charge‐carrier mobility of the pentacene transistors did not decrease. The distinguished performance makes NHCs as excellent alternatives to thiols as metal modifiers for the application in organic field‐effect transistors (OFETs).
Self‐Assembly of Azobenzene Derivatives into Organogels and Photoresponsive Liquid Crystals
Authors: Wang Hongyan , Han Yi , Yuan Wei , Wu Mengjiao , Chen Yulan
Published: February 2018

A new class of coil–rod–coil molecules with an azobenzene core was synthesized. They were found to form robust organogels in several organic solvents. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), FTIR spectroscopy, UV/Vis absorption spectroscopy, 1H NMR spectroscopy, and X‐ray diffraction (XRD) revealed that in these organogels, the molecules self‐assembled into a nanofiber network with an H‐type aggregation mode under the joint effect of π–π stacking, intermolecular hydrogen bonding, and van der Waals forces. Interestingly, the incorporation of the azobenzene mesogene into the rigid core led to photoisomerizable liquid crystal materials, which exhibited quick responsiveness to light and temperature, along with the trans–cis transition stimulated by UV light and heating.
Virus‐Like Particle Engineering: From Rational Design to Versatile Applications
Authors: Ding Xuanwei , Liu Dong , Booth George , Gao Wei , Lu Yuan
Published: February 2018

As mimicking natural virus structures, virus‐like particles (VLPs) have evolved to become a widely accepted technology used for humans which are safe, highly efficacious, and profitable. Several remarkable advantages have been achieved to revolutionize the molecule delivery for diverse applications in nanotechnology, biotechnology, and medicine. Here, the rational structure design, manufacturing process, functionalization strategy, and emerging applications of VLPs is reviewed. The situation and challenges in the VLP engineering, the key development orientation, and future applications have been discussed. To develop a good VLP design concept, the virus/VLP‐host interactions need to be examined and the screening methods of the VLP stabilization factors need to be established. The functionalization toolbox can be expanded to fabricate smart, robust, and multifunctional VLPs. Novel robust VLP manufacturing platforms are required to deliver vaccines in resource‐poor regions with a significant reduction in the production time and cost. The future applications of VLPs are always driven by the development of emerging technologies and new requirements of modern life.
The fully‐extended conformation in peptides and proteins
Authors: Crisma Marco , Formaggio Fernando , Alemán Carlos , Torras Joan , Ramakrishnan Chandrasekharan , Kalmankar Neha , Balaram Padmanabhan , Toniolo Claudio
Published: February 2018

The intramolecularly H‐bonded, fully‐extended conformation (C5) of an α‐amino acid residue (and the resulting 2.05‐helix obtained via its propagation) is one of the least extensively investigated types of peptide and protein backbone secondary structure. This situation does still currently occur despite its unique ability to enjoy by far the largest separation per residue among peptide conformations. In this article, we offer a detailed update of our present knowledge on this intriguing 3D‐structure of peptides in the crystal state as obtained from recently published investigations, complemented by a statistical analysis for its occurrence in the crystal structures of α‐amino acid derivatives and peptides available in the Cambridge Structural Database. We have expanded this useful information to the results of a bioinformatics analysis performed on this (so far largely unappreciated) conformation authenticated in all proteins solved by X‐ray diffraction to a resolution of ≤ 1.5 Å. In the last section, we describe the results of our DFT calculations on the conformational preferences of a set of homopeptides (from monomer to octamer) based on as many as six proteins and two noncoded, carefully selected, α‐amino acids. From this literature survey integrated by new energy calculations, we have definitely provided strong support to the thesis that this polypeptide 3D‐structure does indeed exist, it should be not neglected in future studies by structural biochemists, and it represents a very attractive, novel backbone for applications for organic, medicinal, and biomaterials chemists.
The association between HSD3B7 gene variant and Parkinson's disease in ethnic Chinese
Authors: Lu Zhong‐Jiao , Wang Ling , Sun Xiao‐Yi , Li Jun‐Ying , Cheng Lan , Li Nan‐Nan , Peng Rong
Published: February 2018

Objectives

Studies at the genomewide level of Parkinson's disease (PD) suggested a significant association between the Hydroxy‐delta‐5‐steroid dehydrogenase, 3 beta‐ and steroid delta isomerase 7 (HSD3B7) gene rs9938550 variant and a decreased risk for PD. But its effect has only been discussed in Caucasian populations, and no phenotypic characteristics were included. To investigate the novel variant for PD in Chinese Han populations, we performed an association analysis of rs9938550 variant in a large cohort.

Methods

Using a case–control methodology, a total of 2,239 subjects (1,072 sporadic patients with PD and 1,167 control) were genotyped and the genetic association was analyzed.

Results

No significant association was found between allele A of rs9938550 and PD in the entire cohort (p = .079). However, the frequency of allele A was lower in late‐onset PD (LOPD) as compared with controls older than 50 years (OR = 0.62, 95% CI: 0.45–0.85, padjust = .002). Relatively lower Unified Parkinson's Disease Rating Scale scores were demonstrated in mid‐ to late‐stage PD with GA + AA genotypes than GG genotype (padjust = .018), while other clinical features were similar between carriers and noncarriers.

Conclusions

Our results support that the HSD3B7 rs9938550 variant, which is likely linked to bile acid biosynthesis, reduces the risk of LOPD in Chinese patients and might induce a benign clinical performance.
Competition for nutrients and light: testing advances in resource competition with a natural phytoplankton community
Authors: Burson Amanda , Stomp Maayke , Greenwell Emma , Grosse Julia , Huisman Jef
Published: February 2018

A key challenge in ecology is to understand how nutrients and light affect the biodiversity and community structure of phytoplankton and plant communities. According to resource competition models, ratios of limiting nutrients are major determinants of species composition. At high nutrient levels, however, species interactions may shift to competition for light, which might make nutrient ratios less relevant. The “nutrient‐load hypothesis” merges these two perspectives, by extending the classic model of competition for two nutrients to include competition for light. Here, we test five key predictions of the nutrient‐load hypothesis using multispecies competition experiments. A marine phytoplankton community sampled from the North Sea was inoculated in laboratory chemostats provided with different nitrogen (N) and phosphorus (P) loads to induce either single resource limitation or co‐limitation of N, P, and light. Four of the five predictions were validated by the experiments. In particular, different resource limitations favored the dominance of different species. Increasing nutrient loads caused changes in phytoplankton species composition, even if the N:P ratio of the nutrient loads remained constant, by shifting the species interactions from competition for nutrients to competition for light. In all treatments, small species became dominant whereas larger species were competitively excluded, supporting the common view that small cell size provides a competitive advantage under resource‐limited conditions. Contrary to expectation, all treatments led to coexistence of diatoms, cyanobacteria and green algae, resulting in a higher diversity of species than predicted by theory. Because the coexisting species comprised three phyla with different photosynthetic pigments, we speculate that niche differentiation in the light spectrum might play a role. Our results show that mechanistic resource competition models that integrate nutrient‐based and light‐based approaches provide an important step forward to understand and predict how changing nutrient loads affect community composition.
Using niche breadth theory to explain generalization in mutualisms
Authors: Batstone Rebecca T. , Carscadden Kelly A. , Afkhami Michelle E. , Frederickson Megan E.
Published: February 2018

For a mutualism to remain evolutionarily stable, theory predicts that mutualists should limit their associations to high‐quality partners. However, most mutualists either simultaneously or sequentially associate with multiple partners that confer the same type of reward. By viewing mutualisms through the lens of niche breadth evolution, we outline how the environment shapes partner availability and relative quality, and ultimately a focal mutualist's partner breadth. We argue that mutualists that associate with multiple partners may have a selective advantage compared to specialists for many reasons, including sampling, complementarity, and portfolio effects, as well as the possibility that broad partner breadth increases breadth along other niche axes. Furthermore, selection for narrow partner breadth is unlikely to be strong when the environment erodes variation in partner quality, reduces the costs of interacting with low‐quality partners, spatially structures partner communities, or decreases the strength of mutualism. Thus, we should not be surprised that most mutualists have broad partner breadth, even if it allows for ineffective partners to persist.
2,4‐Thiazolidinedione as a Bioactive Linker for Ferrocenyl Sugar–Triazole Conjugates: Synthesis, Characterization and Biological Properties
Authors: Shinde Dilip N. , Trivedi Rajiv , Vamsi Krishna Narra , Lingamallu Giribabu , Sridhar Balasubramanian , Khursade Parag S. , Reddy Shetty Prakasham
Published: February 2018

A new series of ferrocenyl sugar–triazole conjugates, derived from d‐xylose, d‐ribose and d‐galactose, linked by a 2,4‐thiazolidinedione moiety, has been prepared. Facile 1,3‐dipolar‐Huisgen coupling reactions of the respective sugar azides with the ferrocenyl 2,4‐thiazolidinedione alkyne units give the corresponding conjugates. These conjugates have been characterized by various spectroscopic techniques, including UV/Vis spectroscopy. The electrochemical analysis exhibits one‐electron reversible oxidation behaviour, except for 5c and 5f, which exhibit quasireversible behaviour. Single‐crystal X‐ray diffraction studies of two of the compounds (2 and 3) are performed to determine their structures. The 2,4‐thiazolidinedione linked ferrocenyl sugar–triazole conjugates exhibit moderate‐to‐good antibacterial and antidiabetic activities.
Azobis[tetrazolide]‐Carbonates of the Lanthanides – Breaking the Gadolinium Break
Authors: Müller Danny , Knoll Christian , Herrmann Andrea , Savasci Gökcen , Welch Jan M. , Artner Werner , Ofner Johannes , Lendl Bernhard , Giester Gerald , Weinberger Peter , Steinhauser Georg
Published: February 2018

A series of rare earth element (REE) mixed‐anion 5,5′‐azobis(1H‐tetrazol‐1‐ide)‐carbonate ([REE2(ZT)2CO3(H2O)10]·2H2O; REE = lanthanides plus yttrium) coordination compounds were synthesized, characterized, and analyzed. Syntheses by simple metathesis reactions under a CO2 atmosphere were carried out at ambient (La–Gd and Ho) and elevated pressures (55 bar; Tb, Dy, Er, Tm, Yb, and Y). The resulting crystalline materials were characterized principally by single‐crystal X‐ray diffraction and vibrational spectroscopy (infrared and Raman). All materials are structurally isotypic, crystallizing in the space group C2/c and show nearly identical spectroscopic properties for all the elements investigated. Cell parameters, bond lengths, and bond angles differ marginally, revealing only a slight variation coinciding with the lanthanide (Ln) contraction, that is, the change in the ionic radii of the trivalent rare earth elements. The herein reported series of rare earth element azobis[tetrazolide]‐carbonates represents a remarkable exception as they are a series of isotypic REE coordination compounds with tetrazolide‐derived ligands unaffected by the “gadolinium break”.
Catalytic C‐Alkylation of Pyrroles with Primary Alcohols: Hans Fischer's Alkali and a New Method with Iridium P,N,P‐Pincer Complexes
Authors: Koller Sebastian , Blazejak Max , Hintermann Lukas
Published: February 2018

Hydrogen‐autotransfer alkylation (HAT or “borrowing‐hydrogen” alkylation) of heteroaromatic compounds has been studied with a range of substrates recently, but pyrroles have been largely absent from such studies. The conditions for HAT alkylations of pyrroles were investigated under a variety of conditions and were found to take place under basic alcoholic conditions (Hans Fischer alkylation) in the absence of transition‐metal catalysts; by means of a heterogeneous Pd/C catalyst in the presence of base; and finally by means of homogeneous transition‐metal catalysis combining a base and iridium pincer complexes generated in situ that have not previously been used in HAT alkylations of heterocycles.
Radical‐Induced, Palladium‐Catalyzed C–H Activation: An Approach to Functionalize 4H‐Benzo[d][1,3]oxazin‐4‐one Derivatives by Using Toluenes, Aldehydes, and Benzyl Alcohols
Authors: Kumar Prashant , Gupta Mohit , Bahadur Vijay , Parmar Virinder S. , Singh Brajendra K.
Published: February 2018

Toluenes, aldehydes, and benzyl alcohols have been utilized in the radical‐induced direct functionalization of 4H‐benzo[d][1,3]oxazin‐4‐one derivatives by using a palladium‐catalyzed C–H activation strategy. The stability, low toxicity, and ease of access to toluenes, aldehydes, and benzyl alcohols have made them suitable candidates for this transformation. The reaction proceeded smoothly with high functional group compatibility and afforded the desired products in moderate to good yields. Mechanistic investigations illustrate the radical pathway and highlight the importance of both catalyst and oxidant.
Identity centrality moderates the relationship between acceptance of group‐based stressors and well‐being
Authors: Crane Monique Frances , Louis Winnifred R. , Phillips Jacqueline K. , Amiot Catherine E. , Steffens Niklas K.
Published: February 2018

Two two‐wave studies were used to examine the proposition that identity centrality enhances the effectiveness of stressor acceptance in the face of group‐based stressors. Study 1 was conducted in newly commencing psychology students (N = 154). Stressor intensity, psychology student identity centrality, and attempted stressor acceptance were measured at two‐time points over 6‐weeks. Study 2 was conducted in a group of early to late career veterinarians (N = 92) and extended Study 1 by assessing stressor frequency as an indicator of the level of demand. Veterinarian identity centrality and stressor acceptance were measured twice over 12‐months. Both studies provided support for the predicted three‐way interaction. Only when Time 1 stressors and identity centrality were both high was stressor acceptance related to a reduction in perceived stressor intensity (Study 1) or burnout symptoms (Study 2) at Time 2. These findings suggest that identity centrality enhances the effectiveness of stressor acceptance for supporting wellbeing and resilience.
Why do we self‐punish? Perceptions of the motives and impact of self‐punishment outside the laboratory
Authors: de Vel‐Palumbo Melissa , Woodyatt Lydia , Wenzel Michael
Published: February 2018

This study explores perceptions of why people punish themselves in response to feelings of moral failure. Experimental research has posited some of self‐punishment's functions, but it remains unclear whether the perceived motives and outcomes for those engaging in spontaneous self‐punishment are fundamentally distinct from those in experimental settings. This study explores and interprets laypersons’ experiences of their own self‐punishment, using qualitative and quantitative data collected in an online survey. Self‐punishers responded to a series of questions examining what kinds of self‐punishment behaviours they engage in and why, and their effects on emotions, cognitions, and relationships. Key themes identified via thematic analysis included self‐punishment as an emotion regulation strategy, as an opportunity to reflect and learn from the transgression, and the notion that self‐punishment becomes normalised. Analysis of these themes suggests that self‐punishment can reflect both psychological avoidance and resolution of problems, and that these two functions have different implications for reconciliation.

Key message

Our analysis of naturalistic self‐punishment experiences revealed dimensions of self‐punishment neglected in the empirical literature, in particular the notion of self‐punishment as an exploration (rather than an evasion) of one's guilt.
Studying the emergence of a new social representation: Changes in thinking about nanotechnologies in early 21st‐century Italy
Authors: Brondi Sonia , Neresini Federico
Published: February 2018

We investigated the emergence of a new social representation (SR) of a techno‐scientific innovation—nanotechnologies—among the Italian public. We reviewed how nanotechnologies entered parliamentary debates and the media agenda in the early third millennium. We conducted cross‐sectional surveys in 2006 (N = 246) and 2011 (N = 486) to examine the emerging SR of nanotechnologies. We sought to observe processes of anchoring and objectification ‘in action’, by analyzing roles of (i) social groups, and (ii) neighboring SRs of science and of technology, over time. Several changes from 2006 to 2011 were identified: From a ‘descriptive’ to an ‘evaluative’ approach; from a ‘neutral’ to a ‘controversial’ issue; from a ‘concrete’ to an ‘abstract’ object; and from a ‘technological’ to a ‘scientific’ phenomenon. We conclude that nanotechnologies finally became ‘relevant enough’ by 2011 to be considered a proper object of SR, and an emerging SR can be observed.
Assessment of the impact of different vegetation patterns on soil erosion processes on semiarid loess slopes
Authors: Feng Tianjiao , Wei Wei , Chen Liding , Rodrigo‐Comino Jesús , Die Chen , Feng Xinran , Ren Kemeng , Brevik Eric C. , Yu Yang
Published: February 2018

Soil erosion hinders the recovery and development of ecosystems in semiarid regions. Rainstorms, coupled with the absence of vegetation and improper land management, are important causes of soil erosion in such areas. Greater effort should be made to quantify the initial erosion processes and try to find better solutions for soil and water conservation. In this research, 54 rainfall simulations were performed to assess the impacts of vegetation patterns on soil erosion in a semiarid area of the Loess Plateau, China. Three rainfall intensities (15 mm h‐1, 30 mm h‐1 and 60 mm h‐1) and six vegetation patterns (arbors‐shrubs‐grass ‐A‐S‐G‐, arbors‐grass‐shrubs ‐A‐G‐S‐, shrubs‐arbors‐grass ‐S‐A‐G‐, shrubs‐grass‐arbors ‐S‐G‐A‐, grass‐shrubs‐arbors ‐G‐S‐A‐ and grass‐arbors‐shrubs ‐G‐A‐S‐) were examined at different slope positions (summits, backslopes and footslopes) in the plots (33.3%, 33.3%, 33.3%), respectively. Results showed that the response of soil erosion to rainfall intensity differed under different vegetation patterns. On average, increasing rainfall intensity by 2 to 4 times induced increases of 3.1 to 12.5 times in total runoff and 6.9 to 46.4 times in total sediment yield, respectively. Moreover, if total biomass was held constant across the slope, the patterns of A‐G‐S and A‐S‐G (planting arbor at the summit position) had the highest runoff (18.34 L m‐2 h‐1) and soil losses (197.98 g m‐2 h‐1), while S‐A‐G had the lowest runoff (5.51 L m‐2 h‐1) and soil loss (21.77 g m‐2 h‐1). As indicated by redundancy analysis (RDA) and Pearson correlation results, a greater volume of vegetation located on the back‐ and footslopes acted as effective buffers to prevent runoff generation and sediment yield. Our findings indicated that adjusting vegetation position along slopes can be a crucial tool to control water erosion and benefit ecosystem restoration on the Loess Plateau and other similar regions of the world. Copyright © 2018 John Wiley & Sons, Ltd.
Benefit‐Cost Analysis and Emerging Technologies
Authors: Mannix Brian
Published: February 2018

Emerging technologies are, by definition, full of surprises: developments that we cannot fully anticipate and that might have some bad outcomes as well as good ones. This presents a challenge for anyone trying to make forward‐looking policy decisions, including those who apply benefit‐cost analysis. BCA is now widely known and used, but it is also widely misunderstood—by many of its advocates as well as its detractors. In this essay, I will begin by examining some of the strengths and weaknesses of BCA as a normative science. Yes, “normative science” is an oxymoron, and the incongruity it speaks to is a source of much of the controversy; BCA is an imperfect answer, but often the best available answer, to the question of how a society should go about making collective but not unanimous choices.

I also want to take a hard look at the question of what we are evaluating. BCA is designed to weigh government actions, to see whether they are in the public interest; it is not designed to evaluate private actions. But if the government action is to approve a private action that otherwise would be prohibited, then the BCA inevitably must evaluate the latter. From the perspective of a government regulator, it is very tempting to shift the burden of proof onto private innovators—to obligate them to seek permission to proceed, and to demonstrate that their proposed actions have acceptable risks and will produce a net social benefit. But such burden‐shifting is not merely an administrative convenience; it has serious economic consequences that need to be examined.
Lessons from Environmental Regulation
Authors: Sinden Amy
Published: February 2018

Much of the most substantive and in‐depth experience with formal cost‐benefit analysis in the public policy realm has occurred in the context of federal environmental regulation in the United States. This experience has many important lessons to teach in the realm of synthetic biology. Indeed, many of the dangers and pitfalls that arise when decision‐makers use formal CBA to evaluate environmental regulation seem likely to arise in the synthetic biology context as well, sometimes in particularly troubling forms. Unfortunately, while in many instances these concerns may well point toward a rejection of formal CBA for synthetic biology, the experience from environmental regulation turns out to be far less helpful in identifying alternative decision‐making tools. Because the decisions that arise in the synthetic biology context have a fundamentally different structure from decisions about environmental regulation, the most useful alternatives from that context do not map easily onto this new context.

It may well be generally true that in the search for decision‐making tools, we should not be looking for a single silver bullet that will work in all public policy realms. Perhaps, instead, different kinds of decision‐making call for different tools. This may be true even within the realm of synthetic biology. I am not entirely sure what the “right” tool is for synthetic biology applications, or even whether a “right” tool exists. But at the end of this essay, I offer a few tentative thoughts about why scenario analysis—a strategic planning tool first developed in the context of military planning following World War II—might be one alternative worth considering.
Integrating Scenario Planning and Cost‐Benefit Methods
Authors: Aldrich Stephen C.
Published: February 2018

By their nature, the most vexing social problems reflect collisions between social and economic interests of parties with highly divergent views and perspectives on the cause and character of what is at issue and the consequences that flow from it. Conflicts around biotechnology applications are good examples of these problems. When considering the potential consequences of proposed biotechnology applications, an enormous range of perspectives arise reflecting the breadth of different and often competing interests with a stake in life's future.

This essay starts from an assumption that the traditional tool of cost‐benefit analysis is not adequate for adjudicating competing claims around the introduction of new biotechnology applications. It tends to require implicit simplifying assumptions that reduce or mask true underlying levels of complexity and uncertainty, and the results it produces deliver a definitive and singular answer, as opposed to a multiplicity of outcomes. In this essay, I describe some of the key elements of formal scenario planning to show how CBA could be redeployed as a supporting tool within the broader decision support methodology of formal scenario planning.
Beyond Cost‐Benefit Analysis in the Governance of Synthetic Biology
Authors: Wallach Wendell , Saner Marc , Marchant Gary
Published: February 2018

For many innovations, oversight fits nicely within existing governance mechanisms; nevertheless, others pose unique public health, environmental, and ethical challenges. Synthetic artemisinin, for example, has many precursors in laboratory‐developed drugs that emulate natural forms of the same drug. The policy challenges posed by synthetic artemisinin do not differ significantly in kind from other laboratory‐formulated drugs. Synthetic biofuels and gene drives, however, fit less clearly into existing governance structures. How many of the new categories of products require new forms of regulatory oversight, or at least extensive forms of testing, remains unclear.

Any effort to improve the governance of synthetic biology should start with a rich understanding of the different possible science‐policy interfaces that could help to inform governance. CBA falls into a subset of the overall range of possibilities, and which interface is appropriate may turn out to depend on context, on the demands of the decision at hand. In what follows, we lay out a typology of interfaces. After that, we turn to the question of how to draw upon the range of possible interfaces and effectively address the factual and moral complexities of emerging technologies. We propose a governance model built around structures that we call “governance coordinating committees.” GCCs are intended to be mechanisms for accommodating the complexities of innovations that have far‐ranging societal impacts. The production of biofuels, for example, could contaminate water supplies and have a destructive environmental impact if not managed correctly. The introduction of a gene drive could have economic and environmental impacts that are not restricted to one nation. Forging appropriate means for determining and evaluating those societal impacts, to the best of a corporation's, industry's, or government's ability, is central to responsible research and innovation. Public policy must be shaped in a manner that accommodates as many concerns as possible and minimizes risks.
CBA and Precaution: Policy‐Making about Emerging Technologies
Authors: Kaebnick Gregory E. , Gusmano Michael K.
Published: February 2018

In the technology assessment literature, the leading alternative to CBA‐like methods is usually held to be precaution, which is understood in various ways but is always about making decisions under conditions of uncertainty. Under such conditions, proponents of precaution commonly hold, a straightforward tallying of potential outcomes does not seem possible. Since CBA aims to tally up outcomes to determine which outcome would produce the greatest public benefit, precaution begins to look like, not just an alternative to CBA, but an incompatible alternative.

Nonetheless, some of the better‐known formulations of a precautionary principle expressly call for combining precaution with assessment of costs and benefits. This essay examines the possible intersection of precaution and CBA. It argues that a moderate kind of CBA is a necessary part of a moderate kind of precaution. The existing proposals for integrating CBA and precaution start with an assumption that the integrative task consists in combining decision tools that generate (contrasting) substantive guidance. An alternative approach, explored here, starts with the idea that precaution is not a decision‐generating tool. Rather, it is a way of organizing the thinking that leads eventually to substantive conclusions. The appropriate policy response is reached not by applying a principle but by studying the situation—the proposed action and the problem it is meant to address—and developing recommendations tailored to it. What makes the thinking precautionary is that it emphasizes certain questions—about risk, uncertainty, and values—that CBA tends to suppress. So understood, precaution may well slow the science but is not intrinsically opposed to science or innovation. It can be understood, in fact, as continuous with the science because the contextual understanding of the science and the problems it is meant to address would emerge—in part—from a close engagement with the science.
Human papilloma virus genotyping for the cross‐sectional and longitudinal probability of developing cervical intraepithelial neoplasia grade 2 or more
Authors: Del Mistro Annarosa , Adcock Rachael , Carozzi Francesca , Gillio‐Tos Anna , De Marco Laura , Girlando Salvatore , Rizzolo Raffaella , Frayle Helena , Trevisan Morena , Sani Cristina , Burroni Elena , Giorgi Rossi Paolo , Cuzick Jack , Ronco Guglielmo ,   the New Technologies for Cervical CancerWorking Group
Published: February 2018

Human papilloma virus (HPV) testing is more sensitive but less specific than cytology. We evaluated stand‐alone genotyping as a possible triage method. During a multicentre randomised controlled trial comparing HPV testing to conventional cytology, HPV‐positive women were referred to colposcopy and followed up if no high‐grade lesion was detected. HPV‐positive samples were genotyped by GP5+/GP6+ primed polymerase chain reaction followed by reverse line blot. Genotypes were hierarchically ordered by positive predictive value (PPV) for CIN grade 2 or more (CIN2+), and grouped by cluster analysis into three groups (A, B and C in decreasing order). Receiver operating characteristic curves were computed. Among 2,255 HPV‐positive women with genotyping, 239 CIN2+ (including 113 CIN3+) were detected at baseline or during a 3‐year follow‐up. HPV33 had the highest PPV with CIN2+ and CIN3+ as the endpoint and when considering lesions detected at baseline or also during follow‐up. HPV16 and HPV35 were the second and third, respectively. Cross‐sectional sensitivity for CIN2+ at baseline was 67.3% (95% CI 59.7–74.2), 91.8% (95% CI 86.6–95.5) and 94.7% (95% CI 90.2–97.6), respectively, when considering as “positive” any of the HPV types in group A (33, 16 and 35), A or B (31, 52, 18, 59 and 58) and A or B or C (39, 51, 56, 45 and 68). The corresponding cross‐sectional PPVs for CIN2+ were 15.8% 95% (CI 13.2–18.7), 12.0% (95% CI 10.3–13.9) and 9.6% (95% CI 8.2–11.1), respectively. HPV33, 16 and 35 confer a high probability of CIN2+ but this rapidly decreases when adding other genotypes.
Tunable poly(methacrylic acid‐co‐acrylamide) nanoparticles through inverse emulsion polymerization
Authors: Zhong Justin X. , Clegg John R. , Ander Eric W. , Peppas Nicholas A.
Published: February 2018

Environmentally responsive biomaterials have played key roles in the design of biosensors and drug delivery vehicles. Their physical response to external stimuli, such as temperature or pH, can transduce a signal or trigger the release of a drug. In this work, we designed a robust, highly tunable, pH‐responsive nanoscale hydrogel system. We present the design and characterization of poly(methacrylic acid‐co‐acrylamide) hydrogel nanoparticles, crosslinked with methylenebisacrylamide, through inverse emulsion polymerization. The effects of polymerization parameters (i.e., identities and concentrations of monomer and surfactant) and polymer composition (i.e., weight fraction of ionic and crosslinking monomers) on the nanoparticles’ bulk and environmentally responsive properties were determined. We generated uniform, spherical nanoparticles which, through modulation of crosslinking, exhibit a volume swelling of 1.77–4.07, relative to the collapsed state in an acidic environment. We believe our system has potential as a base platform for the targeted, injectable delivery of hydrophilic therapeutics. With equal importance, however, we hope that our systematic analysis of the individual impacts of polymerization and purification conditions on nanoparticle composition, morphology, and performance can be used to expedite the development of alternate hydrophilic nanomaterials for a range of biomedical applications. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1677–1686, 2018.
Evaluation of a recombinant multiepitope antigen for diagnosis of hepatitis C virus: A lower cost alternative for antigen production
Authors: Thomasini Ronaldo Luis , Souza Hortencia Gisele Amaro , Bruna‐Romero Oscar , Totola Antonio Helvecio , Gonçales Neiva Sellan Lopes , Lima Cristiano Xavier , Teixeira Mauro Martins
Published: February 2018

Background

The most of the hepatitis C‐infected patients remain undiagnosed until they develop severe liver damage or submitted for serological screening.

Objective

To evaluate a recombinant multiepitope protein for detection of IgG anti‐hepatitis C virus. Method: A synthetic gene was cloned, expressed in Escherichia coli, and the recombinant protein was purified. Human serum panel consisted of 88 positives (20 HCV genotyped) and 376 negatives for hepatitis C, 6 positives for human acquired immunodeficiency virus, 6 syphilis positives, 6 hepatitis B positives were tested by IgG antihepatitis C virus using the protein by enzyme‐linked immunosorbent assay. In addition, 20 positive (all genotyped samples) and 20 negative samples were also tested by immunoblot and dot blot assays.

Results

Positive hepatitis C sera were strongly reactive against the protein by immunoblot assay. In the dot blot assay, positive sera were reactive until 1:1000 dilution and there were no false positive results in the hepatitis C negative sera. In the enzyme‐linked immunosorbent assay, positive and negative sera had significant discrimination. No cross‐reaction was observed in samples positive for syphilis; human acquired immunodeficiency virus and hepatitis B. All 20 genotyped samples were positive by the three methods.

Conclusion

The multiepitope protein used here has a lower cost compared to production of each antigen separately and could be an alternative for the serological diagnosis of hepatitis C.
Preclinical evaluation of a semi‐automated and rapid commercial electrophoresis assay for von Willebrand factor multimers
Authors: Pikta Marika , Zemtsovskaja Galina , Bautista Hector , Nouadje Georges , Szanto Timea , Viigimaa Margus , Banys Valdas
Published: February 2018

Background

The von Willebrand factor (VWF) multimer test is required to correctly subtype qualitative type 2 von Willebrand disease (VWD). The current VWF multimer assays are difficult, nonstandardized, and time‐consuming. The purpose of this study was to evaluate the clinical utility of the commercial VWF multimer kit by Sebia (Lisses, France), an electrophoresis technique yielding same‐day results.

Methods

Ten healthy volunteer plasma samples, in‐house reference plasma (IRP) and commercial normal plasma (CNP) samples, 10 plasma samples from patients with a known VWD type, 1 hemophilia A plasma sample, and 7 external quality assurance (EQA) samples were analyzed using the commercial VWF multimer kit. Additional coagulation testing included measurements of VWF antigen (VWF:Ag), VWF activity (VWF:Ac), and FVIII activity (FVIII:C).

Results

The CNP results revealed a relative loss of the highest molecular weight multimers; therefore, IRP was preferred as the reference sample. The interpretations of 10 patients with a known VWD type could be successfully reproduced and agreed with previous VWF multimer results. In all EQA surveys, the multimer results and final VWD diagnosis agreed with expert opinion.

Conclusions

The VWF multimer assay by Sebia is easy to perform and can be successfully implemented in any clinical laboratory for second‐stage evaluation of VWD. The resolution power of multimer distribution is adequate to correctly classify VWD types 1, 2A, 2B, and 3.