bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure of a monolayer of molecular rotors on aqueous subphase from grazing-incidence X-ray diffraction
Authors: Kaleta Jiří , Wen Jin , Magnera Thomas F. , Dron Paul I. , Zhu Chenhui , Michl Josef
Published: March 2018

Significance

The so-far-unknown 2D ferroelectric assemblies of dipolar molecular rotors would be of considerable interest for miniaturization of analog electronics. We have prepared a monolayer of such rod-shaped rotors on an aqueous surface and used grazing-incidence X-ray scattering to determine that its structure meets theoretical requirements for ferroelectricity perfectly. The dipoles, averaged between the three nearest neighbors, stand 0.83 nm apart in a horizontal triangular grid and their rotation axes are vertical. One deck of interlocked triptycenes is located above and one below the dipoles, and on the average seven molecules of water are present near each dipole. It remains to be seen whether the structure can be transferred to an insulator surface undisturbed and is indeed ferroelectric.
The acquisition of L2 speaking
Authors: Lowie Wander , Verspoor Marjolijn H. , van Dijk Marijn
Published: March 2018

The complex dynamic systems theory approach to second language development has great explanatory power in accounting for the development of speaking as an emergent process. CDST approaches focus on the process of development, rather than on the products of learning, and often include the learner’s variability over time as an important source of information. In this chapter a CDST perspective is given of speaking in a second language. The individually owned and variable process of speaking development is illustrated with longitudinal speaking data of identical twins as they learn English as a second language in Taiwan. Our observations emphasize the individual nature of the development of speaking in a second language, which has important implications for effective language teaching for L2 speaking.
Amari/anmari/anma and totemo/tottemo in history and discourse
Authors: Shinzato Rumiko
Published: March 2018

This chapter first presents the distributional patterns of totemo and amari as positive polarity items (PPIs) and negative polarity items (NPIs) in a present-day spoken corpus, by paying due attention to their morphophonological variants, tottemo and anmari/anma. It also analyzes ‘prefabs’ (Bybee 2006) they form as PPI and NPI. Second, it delineates the diachronic development of totemo from NPI to PPI and that of amari from PPI to NPI, and offers an explanatory account incorporating three concepts: counter-expectation (Traugott 1999), structural reanalysis and bifurcation/divergence (Bolinger 1968). In a theoretical context of polarity studies, the paper supports Hoeksema’s (2012) stance that comprehensive accounts need both a syntagmatic relationship (licenser-licensee) as well as a paradigmatic relationship with other similar items in competition.
Genre and the cultural realms of taste in Japanese, Korean, and U.S. online recipes
Authors: Strauss Susan , Chang Heesun , Matsumoto Yumi
Published: March 2018

This chapter investigates the language, culture, and the discourse of food in Japan, Korea, and the United States, as prototypical exemplars of Western culture (U.S.) and Eastern culture (Japan and Korea). We compare and contrast patterns of discursive representations of food and social interaction using the broad analytic unit of genre. The online cooking recipe contains complex discourse about food as well as reader/user commentary. Genre analysis of this type, including the socially organized interactional exchanges between members of socio-cultural groups, provides insights into praxis – and can serve as robust resources for socialization of novices e.g., students of foreign language, as they come to understand the macro and micro levels of discourse qua social practice.
Rescue Therapy for Procedural Complications Associated With Deployment of Flow-Diverting Devices in Cerebral Aneurysms
Authors: Al-Mufti Fawaz , Amuluru Krishna , Cohen Eric R , Patel Vikas , El-Ghanem Mohammad , Wajswol Ethan , Dodson Vincent , Al-Marsoummi Sarmad , Majmundar Neil , Dangayach Neha S , Nuoman Rolla , Gandhi Chirag D
Published: March 2018

Flow diverting devices (FDDs) have revolutionized the treatment of morphologically complex intracranial aneurysms such as wide-necked, giant, or fusiform aneurysms. Although FDDs are extremely effective, they carry a small yet significant risk of intraprocedural complications. As the implementation of these devices increases, the ability to predict and rapidly treat complications, especially those that are iatrogenic or intraprocedural in nature, is becoming increasingly more necessary.

Our objective in this paper is to provide a descriptive summary of the various types of intraprocedural complications that may occur during FDDs deployment and how they may best be treated. A systematic and qualitative review of the literature was conducted using electronic databases MEDLINE and Google Scholar. Searches consisted of Boolean operators “AND” and “OR” for the following terms in different combinations: “aneurysm,” “endovascular,” “flow diverter,” “intracranial,” and “pipeline.”

A total of 94 papers were included in our analysis; approximately 87 of these papers dealt with periprocedural endovascular (mainly related to FDDs) complications and their treatment; 7 studies concerned background material. The main categories of periprocedural complications encountered during deployment of FDDs are failure of occlusion, parent vessel injury and/or rupture, spontaneous intraparenchymal hemorrhage, migration or malposition of the FDDs, thromboembolic or ischemic events, and side branch occlusion

Periprocedural complications occur mainly due to thromboembolic events or mechanical issues related to device deployment and placement. With increasing use and expanding versatility of FDDs, the understanding of these complications is vital in order to effectively manage such situations in a timely manner.
Effect of Therapeutic Hypothermia Initiated After 6 Hours of Age on Death or Disability Among Newborns With Hypoxic-Ischemic Encephalopathy: A Randomized Clinical Trial
Authors: Laptook Abbot R. , Shankaran Seetha , Tyson Jon E. , Munoz Breda , Bell Edward F. , Goldberg Ronald N. , Parikh Nehal A. , Ambalavanan Namasivayam , Pedroza Claudia , Pappas Athina , Das Abhik , Chaudhary Aasma S. , Ehrenkranz Richard A. , Hensman Angelita M. , Van Meurs Krisa P. , Chalak Lina F. , Hamrick Shannon E. G. , Sokol Gregory M. , Walsh Michele C. , Poindexter Brenda B. , Faix Roger G. , Watterberg Kristi L. , Frantz Ivan D. , Guillet Ronnie , Devaskar Uday , Truog William E. , Chock Valerie Y. , Wyckoff Myra H. , McGowan Elisabeth C. , Carlton David P. , Harmon Heidi M. , Brumbaugh Jane E. , Cotten C. Michael , Sánchez Pablo J. , Hibbs Anna Maria , Higgins Rosemary D.
Published: March 2018

(Abstracted from JAMA 2017;318(16):1550–1560)

Hypoxic-ischemic neonatal encephalopathy can cause mortality and devastating lifelong cerebral palsy, neurosensory deficits, and cognitive impairments in neonates. Therapeutic hypothermia initiated within 6 hours after birth has been found to reduce the risk of death or disability at 18 months for hypoxic-ischemic encephalopathy.
Effect of Preconception Impaired Glucose Tolerance on Pregnancy Outcomes in Women With Polycystic Ovary Syndrome
Authors: Wei Daimin , Zhang Bo , Shi Yuhua , Zhang Lin , Zhao Shigang , Du Yanzhi , Xu Lizhen , Legro Richard S. , Zhang Heping , Chen Zi-Jiang
Published: March 2018

(Abstracted from J Clin Endocrinol Metab 2017;102:3822–3829)

Intrinsic insulin resistance is common in women with polycystic ovary syndrome (PCOS), and it is recommended that they undergo an oral glucose tolerance test (OGTT) to screen for diabetes. However, there is no consensus on whether impaired glucose tolerance (IGT) affects pregnancy outcomes.
Emergence of Nontuberculous Mycobacterial Lymphadenitis in Children After the Discontinuation of Mandatory Bacillus Calmette and GuÉrin Immunization in France
Authors: Lacroix Adèle , Piau Caroline , Lanotte Philippe , Carricajo Anne , Guillouzouic Aurelie , Peuchant Olivia , Cady Anne , Dupin Clarisse , Fangous Marie-Sarah , Martin Christian , Cariou Marie-Estelle , Le Gall Florence , Bemer Pascale , Tattevin Pierre
Published: March 2018

Eighty-five children were diagnosed with culture-confirmed nontuberculous mycobacterial cervical lymphadenitis within the MYCOMED surveillance network from 2004 to 2013. The mean incidence sharply increased from 0.57 to 3.7 per 100,000 children per year, after the discontinuation of mandatory bacillus Calmette and Guérin immunization in 2007. Cases were documented as Mycobacterium avium (62.3%), Mycobacterium intracellulare (15.3%) and Mycobacterium lentiflavum (12.9%). Outcome was favorable in all, with or without surgery or antimycobacterial treatment.
How central is central poststroke pain? The role of afferent input in poststroke neuropathic pain: a prospective, open-label pilot study
Authors: Haroutounian Simon , Ford Andria L. , Frey Karen , Nikolajsen Lone , Finnerup Nanna B. , Neiner Alicia , Kharasch Evan D. , Karlsson Pall , Bottros Michael M.
Published: March 2018

Central poststroke pain (CPSP) is a neuropathic pain disorder, the underlying mechanisms of which are not well understood. It has been suggested that stroke-associated loss of inhibitory neurons in the spinothalamic tract causes disinhibition of thalamic neurons, which autonomously generate ectopic nociceptive action potentials responsible for the pain experience. We hypothesized that CPSP is a result of misinterpretation of afferent sensory input by the sensitized neurons within the brain, rather than generated spontaneously by the damaged central nervous system (CNS) neurons. To test this hypothesis, we prospectively recruited 8 patients with definite CPSP affecting at least 1 extremity. In an open-label intervention, an ultrasound-guided peripheral nerve block with lidocaine was performed to block afferent sensory input from a painful extremity. Spontaneous and evoked pain, neuropathic pain descriptors, and lidocaine plasma concentrations were measured. The blockade of peripheral sensory input resulted in complete abolition of pain in 7 of the 8 subjects within 30 minutes (the primary outcome measure of the study), and >50% pain relief in the remaining participant. Median (interquartile range) spontaneous pain intensity changed from 6.5 (4.3-7.0) at baseline to 0 (0-0) after the block (P = 0.008). All mechanical/thermal hypersensitivity was abolished by the nerve block. The results suggest that it is unlikely that CPSP is autonomously generated within the CNS. Rather, this pain is dependent on afferent input from the painful region in the periphery, and may be mediated by misinterpretation of peripheral sensory input by sensitized neurons in the CNS.
Linking Psychological Strain and Suicide Ideation
Authors: Zhang Jie , Liu Yuxin , Zhang Jianwei , Chen Chen
Published: March 2018

Psychosocial causes of suicidal ideation among those who do not have diagnosable mental illnesses remain largely unexplored. Synthesizing the strain theory of suicide and self-determination theory, this research tested a multiple mediator model linking psychological strain with suicidal ideation via three basic psychological need satisfaction. Data from 750 professional employees in China support for the partially mediated effects of psychological strain via need satisfaction of competence and relatedness. These findings contribute to understanding Chinese employees' suicidal ideation from positive psychology perspective that is distinct from what is known from psychopathology.
Impact of Music Therapy on Hospitalized Patients Post-Elective Orthopaedic Surgery
Authors: Gallagher Lisa M. , Gardner Vickie , Bates Debbie , Mason Shelley , Nemecek Jeanine , DiFiore Jacquelyn Baker , Bena James , Li Manshi , Bethoux Francois
Published: March 2018

BACKGROUND:

Music therapy (MT) research has demonstrated positive effects on fatigue, depressed mood, anxiety, and pain in perioperative care areas. However, there has been limited research on the effects of MT for surgical patients on orthopaedic units.

PURPOSE:

The purpose of this study was to understand the impact of MT sessions on post-elective orthopaedic surgery patients' pain, mood, nausea, anxiety, use of narcotics and antiemetics, and length of stay.

METHODS:

This was a randomized controlled study with an experimental arm (MT sessions) and a control arm (standard medical care). Patients received MT within 24 hours of admission to the unit, as well as every day of their stay. Same-day pre- and postdata were collected 30 minutes apart for both arms, including patient self-reported mood, pain, anxiety, and nausea. Use of medications and length of stay were gleaned from the electronic medical record.

RESULTS:

Data were obtained for 163 patients, age 60.5 ± 11.1 years, 56% of whom were male. Joints targeted by surgeries were hips (54%), knees (42%), and shoulders (4%). There were significantly greater changes favoring the MT group on Day 1 (pain, anxiety, and mood), Day 2 (pain, anxiety, mood, and nausea), and Day 3 (pain, anxiety, and mood). Among participants with a pre–pain score of 2 or more on Day 1, a decrease of at least 2 points was noted in 36% of the MT group and 10% of the control group (P < .001). Overall, 73% of MT patients versus 41% of control patients reported improved pain (P < .001). No significant between-group differences in medications or length of stay were noted.

CONCLUSIONS:

We observed greater same-day improvements of pain, emotional status, and nausea with MT sessions, compared to usual care, in patients hospitalized after elective orthopaedic surgeries. Effects on narcotic and antiemetic usage, as well as length of stay, were not observed. More research needs to be conducted to better understand the benefits of MT pre- and post-elective orthopaedic surgery.
Does anthrax antitoxin therapy have a role in the treatment of inhalational anthrax?
Authors: Vietri Nicholas J.
Published: March 2018

Purpose of review

Inhalational anthrax is a rare disease and Bacillus anthracis is a likely pathogen to be used in a biological attack. The lack of clinical experience with anthrax has led experts to develop treatment guidelines. These guidelines recommend anthrax antitoxin to be used in conjunction with antibiotics for the treatment of patients with systemic anthrax infection, yet there is still a lack of human or animal data to support this recommendation.

Recent findings

The U.S. Food and Drug Administration-approved anthrax antitoxins in 2012, 2015, and 2016. These products have been stockpiled for use in a public health emergency. Although efficacy is high when given early, their efficacy diminishes quickly when given after the development of bacteremia. Animal studies showing a significant incremental benefit of antitoxin therapy when combined with antibiotic therapy were not required by the U.S. Food and Drug Administration for product approval.

There is no conclusive evidence demonstrating that anthrax antitoxin therapy, when combined with a therapeutic course of antibiotics provides a survival benefit in inhalational anthrax. Additional research is needed in improved anthrax-antitoxin therapies, novel small molecule toxin inhibitors that act intracellularly, and studies of supportive care such as hemodynamic and ventilatory support, to improve the survival for inhalational anthrax patients and help mitigate the threat caused by the misuse of B. anthracis.
The impact of malnutrition on childhood infections
Authors: Walson Judd L. , Berkley James A.
Published: March 2018

Purpose of review

Almost half of all childhood deaths worldwide occur in children with malnutrition, predominantly in sub-Saharan Africa and South Asia. This review summarizes the mechanisms by which malnutrition and serious infections interact with each other and with children's environments.

Recent findings

It has become clear that whilst malnutrition results in increased incidence, severity and case fatality of common infections, risks continue beyond acute episodes resulting in significant postdischarge mortality. A well established concept of a ‘vicious-cycle’ between nutrition and infection has now evolving to encompass dysbiosis and pathogen colonization as precursors to infection; enteric dysfunction constituting malabsorption, dysregulation of nutrients and metabolism, inflammation and bacterial translocation. All of these interact with a child's diet and environment. Published trials aiming to break this cycle using antimicrobial prophylaxis or water, sanitation and hygiene interventions have not demonstrated public health benefit so far.

As further trials are planned, key gaps in knowledge can be filled by applying new tools to re-examine old questions relating to immune competence during and after infection events and changes in nutritional status; and how to characterize overt and subclinical infection, intestinal permeability to bacteria and the role of antimicrobial resistance using specific biomarkers.
Surgical Treatment of Nonsyndromic Unicoronal Craniosynostosis
Authors: Alford Jake , Derderian Christopher A. , Smartt James M.
Published: March 2018

Purpose:

Unicoronal synostosis (UCS) remains one of the most difficult craniofacial conditions to treat. This review attempts to consolidate all existing literature from the past 25 years that has investigated surgical treatment of nonsyndromic UCS. Additional attention is paid to specific areas of controversy regarding surgical management and evaluation of UCS: outcomes of fronto-orbital advancement (FOA) versus endoscopic strip craniectomy (ESC), emergence of spring-associated cranioplasty for craniosynostosis, and morphologic assessment metrics.

Methods:

A literature search from 1992 to 2017 was performed with a defined search strategy and manual screening process. About 24 studies were included in the final review.

Results:

There is inconsistency among studies in measuring outcomes. Despite wide utilization, FOA produces mixed results, especially when looking at long-term outcomes. Preliminary data suggest advantages to using ESC over FOA with regard to facial symmetry, postoperative strabismus, and operating time. Distraction osteogenesis has long been utilized in Asia and is now being actively studied in the United States. Data on spring-assisted cranioplasty are lacking. Long-term results at skeletal maturity for many of these techniques are lacking.

Discussion:

Despite some promising results, methods of measurement are inconsistent and long-term data are lacking. All future research in this area would benefit from consistent and standardized reporting of data, including perioperative statistics and reproducible 3-dimensional computed tomography craniofacial measurements. Additionally, no definitive recommendations can be made until data at skeletal maturity are studied, and all studies would benefit from long-term follow-up data.
Divergent gene expression among phytoplankton taxa in response to upwelling
Authors: Lampe Robert H. , Cohen Natalie R. , Ellis Kelsey A. , Bruland Kenneth W. , Maldonado Maria T. , Peterson Tawnya D. , Till Claire P. , Brzezinski Mark A. , Bargu Sibel , Thamatrakoln Kimberlee , Kuzminov Fedor I , Twining Benjamin S. , Marchetti Adrian
Published: March 2018

Frequent blooms of phytoplankton occur in coastal upwelling zones creating hotspots of biological productivity in the ocean. As cold, nutrient-rich water is brought up to sunlit layers from depth, phytoplankton are also transported upwards to seed surface blooms that are often dominated by diatoms. The physiological response of phytoplankton to this process, commonly referred to as shift-up, is characterized by rapid growth rates and increases in nitrate assimilation. To examine the molecular underpinnings behind this phenomenon, metatranscriptomics was applied to a simulated upwelling experiment using natural phytoplankton communities from the California Upwelling Zone. An increase in diatom growth following five days of incubation was attributed to the generaChaetocerosandPseudo-nitzschia. Here we show that certain bloom-forming diatoms exhibit a distinct transcriptional response that coordinates shift-up where diatoms exhibited the greatest transcriptional change following upwelling; however, comparison of coexpressed genes exposed overrepresentation of distinct sets within each of the dominant phytoplankton groups. The analysis revealed that diatoms frontload genes involved in nitrogen assimilation likely in order to outcompete other groups for available nitrogen during upwelling events. We speculate that the evolutionary success of diatoms may be due, in part, to this proactive response to frequently encountered changes in their environment.
Neurodynamic explanation of inter-individual and inter-trial variability in cross-modal perception
Authors: Kumar G. Vinodh , Dutta Shrey , Talwar Siddharth , Roy Dipanjan , Banerjee Arpan
Published: March 2018

A widely used experimental design in multisensory integration is the McGurk paradigm that entail illusory (cross-modal) perception of speech sounds when presented with incongruent audio-visual (AV) stimuli. However, the distribution of responses across trials and individuals is heterogeneous and not necessarily everyone in a given group of individuals perceives the effect. Nonetheless, existing studies in the field primarily focus on addressing the correlation between subjective behavior and cortical activations to reveal the neuronal mechanisms underlying the perception of McGurk effect, typically in the “frequent perceivers”. Additionally, a solely neuroimaging approach does not provide mechanistic explanation for the observed inter-trial or inter-individual heterogeneity. In the current study we employ high density electroencephalogram (EEG) recordings in a group of 25 human subjects that allow us to distinguish “frequent perceivers” from “rare perceivers” using behavioral responses as well as from the perspective of large-scale brain functional connectivity (FC). Using global coherence as a measure of large-scale FC, we find that alpha band coherence, a distinctive feature in frequent perceivers is absent in the rare perceivers. Secondly, a decrease in alpha band coherence and increase in gamma band coherence occur during illusory perception trials in both frequent and rare perceivers. Source analysis followed up with source time series reconstructions reveals a large scale network of brain areas involving frontal, temporal and parietal areas that are involved in network level processing of cross-modal perception. Finally, we demonstrate that how a biophysically realistic computational model representing the interaction among key neuronal systems (visual, auditory and multisensory cortical regions) can explain the empirical observations. Each system involves a group of excitatory and inhibitory Hindmarsh Rose neurons that are coupled amongst each other. Large-scale FC between areas is conceptualized using coupling functions and the identity of a specific system, e.g., visual/ auditory/ multisensory is chosen using empirical estimates of the time-scale of information processing in these systems. The model predicts that the disappearance of alpha band coherence observed in rare perceivers stems from a negligible direct A-V (audio-visual) coupling however, an increase in indirect interaction via multisensory node leads to enhanced gamma band and reduced alpha band coherences observed during illusory perception. Overall, we establish the mechanistic basis of large-scale FC patterns underlying cross-modal perception.
Whole-exome sequencing identified rare variants associated with body length and girth in cattle
Authors: Chen Yan , Du Min , Liu Yining , Gao Xue , Zhang Wengang , Xu Ling , Zhang Lupei , Gao Huijiang , Xu Lingyang , Zhu Bo , Zhao Min , Li Junya
Published: March 2018

Body measurements can be used in determining body size to monitor the cattle growth and examine the response to selection. Despite efforts putting into the identification of common genetic variants, the mechanism understanding of the rare variation in complex traits about body size and growth remains limited. Here, we firstly performed GWAS study for body measurement traits in Simmental cattle, however there were no SNPs exceeding significant level associated with body measurements. To further investigate the mechanism of growth traits in beef cattle, we conducted whole exome analysis of 20 cattle with phenotypic differences on body girth and length, representing the first systematic exploration of rare variants on body measurements in cattle. By carrying out a three-phase process of the variant calling and filtering, a sum of 1158, 1151, 1267, and 1303 rare variants were identified in four phenotypic groups of two growth traits, higher/ lower body girth (BG_H and BG_L) and higher/lower body length (BL_H and BL_L) respectively. The subsequent functional enrichment analysis revealed that these rare variants distributed in 886 genes associated with collagen formation and organelle organization, indicating the importance of collagen formation and organelle organization for body size growth in cattle. The integrative network construction distinguished 62 and 66 genes with different co-expression patterns associated with higher and lower phenotypic groups of body measurements respectively, and the two sub-networks were distinct. Gene ontology and pathway annotation further showed that all shared genes in phenotypic differences participate in many biological processes related to the growth and development of the organism. Together, these findings provide a deep insight into rare genetic variants of growth traits in cattle and this will have a promising application in animal breeding.
Survival of the simplest: the cost of complexity in microbial evolution
Authors: Held Torsten , Klemmer Daniel , Lässig Michael
Published: March 2018

The evolution of microbial and viral organisms often generates clonal interference, a mode of competition between genetic clades within a population. In this paper, we show that interference strongly constrains the genetic and phenotypic complexity of evolving systems. Our analysis uses biophysically grounded evolutionary models for an organism’s quantitative molecular phenotypes, such as fold stability and enzymatic activity of genes. We find a generic mode of asexual evolution calledphenotypic interferencewith strong implications for systems biology: it couples the stability and function of individual genes to the population’s global speed of evolution. This mode occurs over a wide range of evolutionary parameters appropriate for microbial populations. It generates selection against genome complexity, because the fitness cost of mutations increases faster than linearly with the number of genes. Recombination can generate a distinct mode of sexual evolution that eliminates the superlinear cost. We show that positive selection can drive a transition from asexual to facultative sexual evolution, providing a specific, biophysically grounded scenario for the evolution of sex. In a broader context, our analysis suggests that the systems biology of microbial organisms is strongly intertwined with their mode of evolution.
Autoreactive T cells preferentially drive differentiation of non-responsive memory B cells at the expense of germinal center maintenance
Authors: Jain Rajiv W , Parham Kate A , Tesfagiorgis Yodit , Craig Heather C , Romanchik Emiliano , Kerfoot Steven M
Published: March 2018

B cell fate decisions within a germinal center (GC) are critical to determining the outcome of the immune response to a given antigen. Here, we characterize GC kinetics and B cell fate choices in a response to the autoantigen myelin oligodendrocyte glycoprotein (MOG), and compare them the response to a standard model foreign antigen (NP-haptenated ovalbumin, NPOVA). Both antigens generated productive primary responses, as evidenced by GC development, circulating antigen-specific antibodies, and differentiation of memory B cells. However, in the MOG response the status of the cognate T cell partner drove preferential B cell differentiation to a memory phenotype at the expense of GC maintenance, resulting in a truncated GC. Reduced plasma cell differentiation was largely independent of T cell influence. Interestingly, memory B cells formed in the MOG GC were unresponsive to secondary challenge and this could not be overcome with T cell help.
Engineered Peptide Barcodes for In-Depth Analyses of Binding Protein Ensembles
Authors: Egloff Pascal , Zimmermann Iwan , Arnold Fabian M. , Hutter Cedric A. J. , Morger Damien , Opitz Lennart , Poveda Lucy , Keserue Hans-Anton , Panse Christian , Roschitzki Bernd , Seeger Markus A.
Published: March 2018

Binding protein generation relies on laborious screening cascades that process candidate molecules individually. To break with this paradigm, we developed NestLink, a binder selection and identification technology able to biophysically characterize thousands of library members at once without handling individual clones at any stage of the process. NestLink builds on genetically fused barcoding peptides, termed flycodes, which are designed for maximal detectability by mass spectrometry and serve as unique molecular identifiers for accurate deep sequencing. We applied NestLink to overcome current limitations of binder generation. Rare binders against an integral membrane protein were identified directly in the cellular environment of a human pathogen. Hundreds of binder candidates were simultaneously ranked according to kinetic parameters. Adverse effects of target immobilization were overcome by selecting nanobodies against an ABC transporter entirely in solution. NestLink may provide a basis for the selection of tailored binder characteristics directly in tissues or in living organisms.
Hydrophobicity drives the systemic distribution of lipid-conjugated siRNAs via lipid transport pathways
Authors: Osborn Maire F. , Coles Andrew H. , Biscans Annabelle , Haraszti Reka A. , Roux Loic , Davis Sarah , Ly Socheata , Echeverria Dimas , Hassler Matthew R. , Godinho Bruno M.D.C. , Nikan Mehran , Khvorova Anastasia
Published: March 2018

Efficient delivery of therapeutic RNA is the fundamental obstacle preventing its clinical utility. Lipid conjugation improves plasma half-life, tissue accumulation, and cellular uptake of small interfering RNAs (siRNAs). However, the impact of conjugate structure and hydrophobicity on siRNA pharmacokinetics is unclear, impeding the design of clinically relevant lipid-siRNAs. Using a panel of biologically-occurring lipids, we show that lipid conjugation modulates siRNA hydrophobicity and governs spontaneous partitioning into distinct plasma lipoprotein classes in vivo. Lipoprotein binding influences siRNA distribution by delaying renal excretion and promoting uptake into lipoprotein receptor-enriched tissues. Lipid-siRNAs elicit mRNA silencing without causing toxicity in a tissue-specific manner. Lipid-siRNA internalization occurs independently of lipoprotein endocytosis, and is mediated by siRNA phosphorothioate modifications. Although biomimetic lipoprotein nanoparticles have been considered for the enhancement of siRNA delivery, our findings suggest that hydrophobic modifications can be leveraged to incorporate therapeutic siRNA into endogenous lipid transport pathways without the requirement for synthetic formulation.
Cs[Tf2N]: a second polymorph with a layered structure
Authors: Stritzinger Jared T. , Droessler Janelle E. , Scott Brian L. , Goff George S.
Published: March 2018

The structural determination of the ionic liquid, caesium bis[(trifluoromethyl)sulfonyl]imide or poly[[μ4-bis[(trifluoromethyl)sulfonyl]imido]caesium(I)], Cs[N(SO2CF3)2] or Cs[Tf2N], reveals a second polymorph that also crystallizes in a layer structure possessing monoclinic P21/c symmetry at 120 K instead of C2/c for the known polymorph [Xue et al. (2002). Solid State Sci.
4, 1535–1545]. The caesium ions in the cationic layers are coordinated by the sulfonyl groups of the bistriflimide molecules from anion layers while the trifluoromethyl groups are oriented in the opposite direction, forming a non-polar surface separating the layers. The layer direction is (100).
2-Fluoro-5-nitroaniline
Authors: Moorthy K. , NizamMohideen M. , Vetrivel S. , Vinoth E. , Arun A.
Published: March 2018

In the title compound, C6H5FN2O2, the dihedral angle between the nitro group and the benzene ring is 3.68 (2)°, and an intramolecular N—H...F hydrogen bond is observed. The crystal packing is consolidated by C—H...O and N—H...O hydrogen bonds; together, these generate [110] double chains.
Occult return, divine grace, and saabui: practising transnational kinship in postsocialist Guinea
Authors: Cohen Adrienne
Published: March 2018

In the Republic of Guinea, where transnational migration has become a critical path to prestige among young urbanites, migrant success abroad is intimately connected to the cultivation of kin ties at home. For performing artists, who were the darlings of Guinea's Socialist Revolution (1958‐84), the experience of migration is uniquely linked to the fall of the socialist state and to the precarity of urban life in contemporary Africa. This article describes how Guinean artists manage distance and uncertainty through three practices: occult aggression, grace‐seeking, and patronage (saabui), which together illustrate the contours and limitations of kinship's efficacy in transnational space. By exploring transnational kinship as an intersubjective and productive practice that can extend beyond obligation or solidarity and into the realm of magic, this article proposes new ways of conceptualizing what it means for migrants to maintain significant connections across national borders.
Plasticity of mycangia in Xylosandrus ambrosia beetles
Authors: Li You , Ruan Yong‐Ying , Stanley Edward L. , Skelton James , Hulcr Jiri
Published: March 2018

Insects that depend on microbial mutualists evolved a variety of organs to transport the microsymbionts while dispersing. The ontogeny and variability of such organs is rarely studied, and the microsymbiont's effects on the animal tissue development remain unknown in most cases. Ambrosia beetles (Coleoptera: Curculionidae: Scolytinae or Platypodinae) and their mutualistic fungi are an ideal system to study the animal–fungus interactions. While the interspecific diversity of their fungus transport organ—mycangia—is well‐known, their developmental plasticity has been poorly described. To determine the ontogeny of the mycangium and the influence of the symbiotic fungus on the tissue development, we dissected by hand or scanned with micro‐CT the mycangia in various developmental stages in five Xylosandrus ambrosia beetle species that possess a large, mesonotal mycangium: Xylosandrus amputatus, Xylosandrus compactus, Xylosandrus crassiusculus, Xylosandrus discolor, and Xylosandrus germanus. We processed 181 beetle samples from the United States and China. All five species displayed three stages of the mycangium development: (1) young teneral adults had an empty, deflated and cryptic mycangium without fungal mass; (2) in fully mature adults during dispersal, the pro‐mesonotal membrane was inflated, and most individuals developed a mycangium mostly filled with the symbiont, though size and symmetry varied; and (3) after successful establishment of their new galleries, most females discharged the bulk of the fungal inoculum and deflated the mycangium. Experimental aposymbiotic individuals demonstrated that the pronotal membrane invaginated independently of the presence of the fungus, but the fungus was required for inflation. Mycangia are more dynamic than previously thought, and their morphological changes correspond to the phases of the symbiosis. Importantly, studies of the fungal symbionts or plant pathogen transmission in ambrosia beetles need to consider which developmental stage to sample. We provide illustrations of the different stages, including microphotography of dissections and micro‐CT scans.
A general framework for globally optimized pagination
Authors: Mittelbach Frank
Published: March 2018

Pagination problems deal with questions around transforming a source text stream into a formatted document by dividing it up into individual columns and pages, including adding auxiliary elements that have some relationship to the source stream data but may allow a certain amount of variation in placement (such as figures or footnotes).

Traditionally, the pagination problem has been approached by separating it into one of micro‐typography (eg, breaking text into paragraphs, also known as h&j) and one of macro‐typography (eg, taking a galley of already formatted paragraphs and breaking them into columns and pages) without much interaction between the two.

While early solutions for both problem areas used simple greedy algorithms, Knuth and Plass introduced in 1981 a global‐fit algorithm for line breaking that optimizes the breaks across the whole paragraph. This algorithm was implemented in (see Computers & Typesetting, Volume B: TeX: The Program by Knuth in 1986) and has since kept its crown as the best available solution for this space. However, for macro‐typography there has been no (successful) attempt to provide a globally optimized page layout: All systems to date (including ) use greedy algorithms for pagination. Various problems in this area have been researched, and the literature documents some prototype development. However, none of them have been made widely available to the research community or ever made it into a generally usable and publicly available system.

This paper is an extended version of the author's work in 2016 originally presented at the 16th ACM Symposium on Document Engineering in Vienna, Austria. It presents a framework for a global‐fit algorithm for page breaking based on the ideas of Knuth/Plass. It is implemented in such a way that it is directly usable without additional executables with any modern installation. It therefore can serve as a test bed for future experiments and extensions in this space. At the same time, a cleaned‐up version of the current prototype has the potential to become a production tool for the huge number of users worldwide.

This paper also discusses 2 already implemented extensions that increase the flexibility of the pagination process (a necessary prerequisite for successful global optimization): the ability to automatically consider existing flexibility in paragraph length (by considering paragraph variations with different numbers of lines) and the concept of running the columns on a double spread a line long or short. It concludes with a discussion of the overall approach, its inherent limitations and directions for future research.
Molecular cloning, characterization, and expression profiles of the Sox3 gene in Chinese loach Paramisgurnus dabryanus
Authors: Xia Xiaohua , Huo Weiran , Wan Ruyan , Wang Peijin , Zhang Linxia , Chang Zhongjie
Published: March 2018

A number of studies have established that in vertebrates, Sox3 is involved in a wide range of developmental processes, including sex differentiation and neurogenesis. However, the exact functions of the Sox3 gene have not been documented so far in teleosts. Here, we cloned the full length cDNA of Sox3 from the teleost fish, Paramisgurnus dabryanus, which we designated PdSox3. Sequence analysis revealed that PdSox3 encodes a hydrophilic protein, and shares high homology with Sox3 in other species, ranging from mammals to fishes. Quantitative real‐time reverse transcription PCR, and in situ hybridization showed that PdSox3 is consistently expressed during embryogenesis, mainly localized in the developing central nervous system. Tissue distribution analyses revealed that PdSox3 is abundant in the adult brain, especially in particle cell layer. Furthermore, PdSox3 expression was higher in gonads, in primary spermatocyte cells, primary oocytes, and previtellogenic oocyte cells. All of these results suggest that PdSox3 plays an important role in early embryonic development, in particular the formation and development of the nervous system, and gonad development, similarly to other vertebrates. This is the first report describing Sox3 gene expression from this species, and the results are necessary to provide fundamental information on both the functional and evolutionary role of Sox3 across different species.
Clinical predictors of Alzheimer's disease progression
Authors: Hishikawa Nozomi , Fukui Yusuke , Takemoto Mami , Sato Kota , Shang Jingwei , Yamashita Toru , Ohta Yasuyuki , Abe Koji
Published: March 2018

Aim

Rates of disease progression differ among patients with Alzheimer's disease (AD), but prognostic predictions remain a challenge. We carried out a clinic‐based retrospective study to investigate the clinical factors for AD progression.

Methods

The 748 AD patients, who attended our hospital for >1 year and were given the Mini‐Mental State Examination (MMSE) at least three times, were divided into three groups according to the annual change rate of MMSE score (G): Aggravater group (G < −2), Stabler group (−2 ≤ G ≤ 2) and Improver group (2 < G). We compared the three groups on cognitive, affective and activities of daily living functions, response to medication, clinical fluctuations, serum levels of metabolic factors, and neuroimaging data.

Results

We found no significant differences in age, sex, educational attainment or body mass index across the groups. The Aggravater group showed better baseline MMSE (P < 0.01) and Abe's behavioral and psychological symptoms of dementia (P < 0.01) scores than the Improver group, but its MMSE improvement after drug treatment was the worst among the three groups (P < 0.01 vs Stabler/Improver). Fluctuations in MMSE (P < 0.01), apathy scale (P < 0.05) and activities of daily living (P < 0.01) scores were smaller in the Improver group than in the Aggravater or Stabler groups. Serum docosahexaenoic acid levels tended to be lower (trend P < 0.05) and voxel‐based specific regional analysis system for Alzheimer's disease Z‐scores tended to be higher (trend P < 0.05) in the Improver group than in the Stabler or Aggravater groups.

Conclusions

Initial responses to medication, fluctuations in cognitive, affective and activities of daily living functions, serum docosahexaenoic acid levels, and medial temporal atrophy are clinical factors related to AD prognosis. Geriatr Gerontol Int 2018; 18: 929–936.
Size matters! Habitat preferences of the wrinkled bark beetle,Rhysodes sulcatus, the relict species of European primeval forests
Authors: Kostanjsek Fran , Sebek Pavel , Baranova Beata , Seric Jelaska Lucija , Riedl Vladan , Cizek Lukas
Published: March 2018

The wrinkled bark beetleRhysodes sulcatusis an endangered saproxylic beetle listed in the European Habitats Directive and in the Bern Convention (AnnexII). It is considered a relict of primeval forests and belongs among the most threatened saproxylic beetles in Europe.

The purpose of this study was to identify the key habitat requirements of the species. The study was carried out at several locations within different forest types in mid elevation forests dominated by oak, beech and spruce and montane beech‐fir forests in the Czech Republic, Slovakia and Croatia.

Coarse woody debris was checked for the presence of the beetle, and parameters of each inspected dead wood unit and its surroundings were recorded, including diameter, length, humidity, insolation, decomposition level and rot type. Surrounding forest characteristics, such as canopy density, main tree species, undergrowth, the amount and quality of the dead wood were also recorded.

The analysis shows that the presence of the beetle is affected mainly by the diameter of dead wood as well as its humidity, asR. sulcatuswas almost exclusively found in large, moist and well rotten fallen logs with a diameter greater than 60 cm. These findings may provide useful guidelines for sustainable forest management, specifically emphasising the need to retain large fallen logs at sites inhabited byR. sulcatuspopulations.
The impact of simulation education on self‐efficacy towards teaching for nurse educators
Authors: Garner S.L. , Killingsworth E. , Bradshaw M. , Raj L. , Johnson S.R. , Abijah S.P. , Parimala S. , Victor S.
Published: March 2018

Aim

The objective of this study was to assess the impact of a simulation workshop on self‐efficacy towards teaching for nurse educators in India. Additionally, we sought to revise and validate a tool to measure self‐efficacy in teaching for use with a global audience.

Background

Simulation is an evidence‐based teaching and learning method and is increasingly used in nursing education globally.

Introduction

As new technology and teaching methods such as simulation continue to evolve, it is important for new as well as experienced nurse educators globally to have confidence in their teaching skills and abilities.

Methods

The study included (1) instrument revision, and measures of reliability and validation, (2) an 8‐h faculty development workshop intervention on simulation, (3) pre‐ and post‐survey of self‐efficacy among nurse educators, and (4) investigation of relationship between faculty socio‐demographics and degree of self‐efficacy.

Results

The modified tool showed internal consistency (r = 0.98) and was validated by international faculty experts. There were significant improvements in total self‐efficacy (P < 0.001) and subscale scores among nurse educators after the simulation workshop intervention when compared to pre‐survey results. No significant relationships were found between socio‐demographic variables and degree of self‐efficacy.

Discussion

Strong self‐efficacy in teaching among nurse educators is crucial for effective learning to occur.

Conclusions and implications for nursing

Results indicated the simulation workshop was effective in significantly improving self‐efficacy towards teaching for nurse educators using an internationally validated tool.

Implications for nursing policy

The Minister of Health in India recently called for improvements in nursing education. Introducing nursing education on simulation as a teaching method in India and globally to improve self‐efficacy among teachers is an example of a strategy towards meeting this call.
Topical propranolol for infantile haemangiomas: a systematic review
Authors: Price A. , Rai S. , Mcleod R.W.J. , Birchall J.C. , Elhassan H.A.
Published: March 2018

Infantile haemangiomas are the most common tumour of infancy. Whilst the majority are left untreated to involute spontaneously, residual skin changes commonly occur, particularly in superficial haemangiomas. The current first‐line treatment for problematic lesions is oral propranolol; however due to the risk of systemic adverse effects, the use of off‐label topical preparations has recently been investigated. Our systematic review was conducted in accordance with PRISMA guidelines. Four databases were searched to identify original articles evaluating the use of topical propranolol as the primary therapy for infantile haemangiomas. Twelve articles with a total of 597 patients and 632 haemangiomas were included. Three topical propranolol preparations were used, creams, ointments and gels and were all prepared by local pharmaceutical laboratories. The concentration of propranolol ranged from 0.5% to 5%. Treatment duration ranged from two weeks to 16.5 months. Overall, 90% of lesions improved following the initiation of topical propranolol. A good or excellent response, defined as a reduction in the size of at least 50%, was seen in 59% of lesions. Earlier initiation of treatment (less than 3 months of age) was associated with improved outcomes. No systemic adverse effects were reported. Minor local reactions were seen in 1.3% of patients. Topical propranolol is safer than oral propranolol, though may be less effective. Topical propranolol may be more suitable for patients with small, superficial haemangiomas at risk of cosmetic sequelae, where the cosmetic or symptomatic impact does not warrant oral propranolol treatment.