bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of Pyranopyrazoles Using Magnetically Recyclable Heterogeneous Iron Oxide‐silica Core‐shell Nanocatalyst
Authors: Soleimani Ebrahim , Jafarzadeh Mohammad , Norouzi Parastoo , Dayou Jedol , Sipaut Coswald Stephen , Mansa Rachel Fran , Saei Parisa
Published: December 2015

The Fe3O4@SiO2 core‐shell nanocatalyst were prepared and efficiently used for four‐component coupling reaction of aromatic aldehydes, malononitrile, ethyl acetoacetate and hydrazine hydrate in water/ethanol mixture. Various aromatic aldehydes possessing electron‐withdrawing and electron‐donating groups in different positions on the ring were successfully transformed to substituted pyranopyrazoles in high yields in short time. The nanocatalyst was easily recovered, and reused five times without significant loss in cata‐ lytic activity and performance. The structure, size and morphology of the nanosized catalyst were studied by various techniques such as Fourier transform infrared spectroscopy, powder X‐ray diffraction, dynamic light scattering and transmission electron microscopy.
Enhanced Cellular Activity in Gelatin‐Poly(Ethylene Glycol) Hydrogels without Compromising Gel Stiffness
Authors: Hoang Thi Thai Thanh , Lee Jung Seok , Lee Yunki , Park Kyung Min , Park Ki Dong
Published: December 2015

Adhesion and proliferation of cells are often suppressed in rigid hydrogels as gel stiffness induces mechanical stress to embedded cells. Herein, the composite hydrogel systems to facilitate high cellular activities are described, while maintaining relatively high gel stiffness. This unusual property is obtained by harmonizing gelatin‐poly(ethylene glycol)‐tyramine (GPT, semisynthetic polymer) and gelatin‐hydroxyphenyl propionic acid conjugates (GH, natural polymer) into hydrogels. A minimum GH concentration of 50% is necessary for cells to be proliferative. GPT is utilized to improve biological stability (>1 week) and gelation time (<20 s) of the hydrogels. These results suggest that deficiency in cellular activity driven by gel stiffness could be overcome by finely tuning the material properties in the microenvironments.

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Convergence theory of exact interpolation scheme for computing several eigenvectors
Authors: Pultarová I.
Published: December 2015

An asymptotic convergence analysis of a new multilevel method for numerical solution of eigenvalues and eigenvectors of symmetric and positive definite matrices is performed. The analyzed method is a generalization of the original method that has recently been proposed by R. Kužel and P. Vaněk (DOI: 10.1002/nla.1975) and uses a standard multigrid prolongator matrix enriched by one full column vector, which approximates the first eigenvector. The new generalized eigensolver is designed to compute
eigenvectors. Their asymptotic convergence in terms of the generalized residuals is proved, and its convergence factor is estimated. The theoretical analysis is illustrated by numerical examples. Copyright © 2015 John Wiley & Sons, Ltd.
Domiciliary noninvasive positive airway pressure therapy in children
Authors: Amin Reshma , Al‐Saleh Suhail , Narang Indra
Published: December 2015

There has been a dramatic increase in the past few decades in the number of children receiving noninvasive positive airway pressure (PAP) therapy at home. Although PAP therapy was first prescribed for children with obstructive sleep apnea, the indications have rapidly widened to include treatment for central hypoventilation syndromes, neuromuscular and chest wall disorders as well as primary respiratory diseases. Given the rapidly expanding use of PAP therapy in children, pediatric pulmonologists need to be familiar with the indications, technical and safety considerations as well as potential complications and challenges that may arise when caring for children using PAP therapy. This review article covers the definition of PAP therapy, modes, interfaces, devices, indications, contraindications, suggested settings, complications as well as the factors influencing the adherence. Pediatr Pulmonol. 2016;51:335–348. © 2015 Wiley Periodicals, Inc.
Diagnostic assays for polyomavirus JC and progressive multifocal leukoencephalopathy
Authors: White Martyn K. , Sariyer Ilker K. , Gordon Jennifer , Delbue Serena , Pietropaolo Valeria , Berger Joseph R. , Khalili Kamel
Published: December 2015

Progressive multifocal leukoencephalopathy (PML) is a devastating and often fatal demyelinating disease of the central nervous system for which effective therapies are lacking. It is caused by the replication of polyomavirus JC (JCV) in the oligodendrocytes and astrocytes leading to their cytolytic death and loss of myelin from the subcortical white matter. While the virus is very common in human populations worldwide, the incidence of the disease is very low and confined almost exclusively to individuals with some form of immunological dysfunction. However, the number of people who constitute the at‐risk population is growing larger and includes individuals with HIV‐1/AIDS and patients receiving immunomodulatory therapies such as multiple sclerosis patients treated with natalizumab. Further adding to the public health significance of this disease are the difficulties encountered in the diagnosis of PML and the lack of useful biomarkers for PML progression. In this review, we examine the diagnostic assays that are available for different aspects of the JCV life cycle, their usefulness and drawbacks, and the prospects for improvements. Copyright © 2015 John Wiley & Sons, Ltd.
Absence of Benefit of Transcatheter Arterial Chemoembolization (TACE) in Patients with Resectable Solitary Hepatocellular Carcinoma
Authors: Ha Tae‐Yong , Hwang Shin , Lee Young‐Joo , Kim Ki‐Hun , Ko Gi‐Young , II Gwon Dong , Ahn Chul‐Soo , Moon Deok‐Bog , Song Gi‐Won , Jung Dong‐Hwan , Lee Han Chu , Lim Young‐Suk , Kim Kang Mo , Shim Ju Hyun , Choi Jeong‐Heon , Lee Sung‐Gyu
Published: December 2015

Background

This study aimed to assess the prognostic impact of preoperative transcatheter arterial chemoembolization (TACE) on long‐term survival outcomes in patients undergoing resection of small solitary hepatocellular carcinoma (HCC).

Methods

Enrolled patients had undergone macroscopic curative resection of solitary 2–5 cm HCC with (n = 105) or without (n = 830; control group) preoperative TACE.

Results

TACE group was divided into subgroups A (n = 68, 1–2 TACEs within 12 months), B (n = 23, ≥3 TACEs within 12 months), and C (n = 14, TACE prior to 12 months). The number of TACE sessions was 1.8 ± 1.6. In TACE A‐C subgroups, pathological response of tumor necrosis >50 % at median post‐TACE period after final TACE was observed in 41 (60.3 %) at 1.9 months, 10 (43.5 %) at 2.1 months, and 2 (14.3 %) at 18.9 months, respectively. The 5‐year tumor recurrence and patient survival rates were 62.8 and 70.4 % in TACE group and 51.4 and 83.4 % in control group, respectively (p ≤ 0.003). Median periods of postoperative tumor recurrence in TACE A‐C subgroups and control group were 35, 13, 14, and 55 months, respectively (p < 0.001); and postoperative survival periods at 75 % survival rate were 51, 38, 51, and 98 months, respectively (p = 0.003). TACE‐induced extensive tumor necrosis did not improve postoperative prognosis in TACE A subgroup (p ≥ 0.053). Postoperative prognosis after preoperative sequential TACE and portal vein embolization was comparable to that of the control group (p ≥ 0.052).

Conclusions

Preoperative TACE for small solitary HCCs may adversely affect post‐resection prognosis, irrespective of pathological responses. Preoperative TACE should be avoided for patients with resectable small HCCs.
Clinical Decision Support Tools for Selecting Interventions for Patients with Disabling Musculoskeletal Disorders: A Scoping Review
Authors: Gross Douglas P. , Armijo-Olivo Susan , Shaw William S. , Williams-Whitt Kelly , Shaw Nicola T. , Hartvigsen Jan , Qin Ziling , Ha Christine , Woodhouse Linda J. , Steenstra Ivan A.
Published: December 2015

PurposeWe aimed to identify and inventory clinical decision support (CDS) tools for helping front-line staff select interventions for patients with musculoskeletal (MSK) disorders.MethodsWe used Arksey and O’Malley’s scoping review framework which progresses through five stages: (1) identifying the research question; (2) identifying relevant studies; (3) selecting studies for analysis; (4) charting the data; and (5) collating, summarizing and reporting results. We considered computer-based, and other available tools, such as algorithms, care pathways, rules and models. Since this research crosses multiple disciplines, we searched health care, computing science and business databases.ResultsOur search resulted in 4605 manuscripts. Titles and abstracts were screened for relevance. The reliability of the screening process was high with an average percentage of agreement of 92.3 %. Of the located articles, 123 were considered relevant. Within this literature, there were 43 CDS tools located. These were classified into 3 main areas: computer-based tools/questionnaires (n = 8, 19 %), treatment algorithms/models (n = 14, 33 %), and clinical prediction rules/classification systems (n = 21, 49 %). Each of these areas and the associated evidence are described. The state of evidentiary support for CDS tools is still preliminary and lacks external validation, head-to-head comparisons, or evidence of generalizability across different populations and settings.ConclusionsCDS tools, especially those employing rapidly advancing computer technologies, are under development and of potential interest to health care providers, case management organizations and funders of care. Based on the results of this scoping review, we conclude that these tools, models and systems should be subjected to further validation before they can be recommended for large-scale implementation for managing patients with MSK disorders.
Stroke Education in Canadian Emergency Medicine Residency Programs
Authors: Harris Devin R. , Teal Philip , Turton Matthew , Lahiffe Brian , Pulfrey Simon
Published: December 2015

Objectives

Stroke and transient ischemic attack (TIA) are common disorders treated by Canadian emergency physicians. The diagnosis and management of these conditions is time-sensitive and complex, requiring that emergency physicians have adequate training. This study sought to determine the extent of stroke and TIA training in Canadian emergency medicine residency programs.

Methods

A two-page survey was emailed to directors of all English-speaking emergency medicine residency programs in Canada. This included both the Fellow of the Royal College of Physicians of Canada (FRCPC) and the College of Family Physicians Enhanced Training [CCFP(EM)] residency programs. The number of mandatory and elective rotations, lectures, and examinations relevant to stroke and TIA were assessed.

Results

Nine FRCPC programs responded (of 11; RR=82%) and 11 CCFP(EM) programs responded (of 18; RR=61%), representing 20 of 29 programs in Canada (RR: 20/29=69%). Mandatory general neurology (3/9) and stroke neurology (2/9) rotations were offered in a minority of FRCPC programs and not at all in CCFP(EM) programs (0/11). Neuroradiology rotations were mandatory in 1/9 FRCPC programs and no CCFP(EM) programs (0/11). Acute ischemic stroke was allocated 3 hours of lecture time per year in all residency programs, regardless of route of training. Despite the fact that 100% of respondents train residents in facilities that administer thrombolysis for stroke, only 1/11 (9%) CCFP(EM) programs and 0/9 FRCPC programs have residents act as stroke team leaders.

Conclusions

Formal training in stroke and TIA is limited in Canadian emergency medicine residency programs. Enhanced training opportunities should be developed as this disease is sudden, life-threatening, and can have disabling or fatal consequences, and therapeutic options are time sensitive.
Boundary conditions for the formation of the Moon
Authors: Reuver M. , de Meijer R.J. , ten Kate I.L. , van Westrenen W.
Published: December 2015

Recent measurements of the chemical and isotopic composition of lunar samples indicate that the Moon's bulk composition shows great similarities with the composition of the silicate Earth. Moon formation models that attempt to explain these similarities make a wide variety of assumptions about the properties of the Earth prior to the formation of the Moon (the proto-Earth), and about the necessity and properties of an impactor colliding with the proto-Earth. This paper investigates the effects of the proto-Earth's mass, oblateness and internal core-mantle differentiation on its moment of inertia. The ratio of angular momentum and moment of inertia determines the stability of the proto-Earth and the binding energy, i.e. the energy needed to make the transition from an initial state in which the system is a rotating single body with a certain angular momentum to a final state with two bodies (Earth and Moon) with the same total angular momentum, redistributed between Earth and Moon. For the initial state two scenarios are being investigated: a homogeneous (undifferentiated) proto-Earth and a proto-Earth differentiated in a central metallic and an outer silicate shell; for both scenarios a range of oblateness values is investigated. Calculations indicate that a differentiated proto-Earth would become unstable at an angular momentum L that exceeds the total angular momentum of the present-day Earth–Moon system (L0) by factors of 2.5–2.9, with the precise maximum dependent on the proto-Earth's oblateness. Further limitations are imposed by the Roche limit and the logical condition that the separated Earth–Moon system should be formed outside the proto-Earth. This further limits the L values of the Earth–Moon system to a maximum of about L/L0 = 1.5, at a minimum oblateness (a/c ratio) of 1.2. These calculations provide boundary conditions for the main classes of Moon-forming models. Our results show that at the high values of L used in recent giant impact models (1.8 < L/L0 < 3.1), the proposed proto-Earths are unstable before (Cuk & Stewart, 2012) or immediately after (Canup, 2012) the impact, even at a high oblateness (the most favourable condition for stability). We conclude that the recent attempts to improve the classic giant impact hypothesis by studying systems with very high values of L are not supported by the boundary condition calculations in this work. In contrast, this work indicates that the nuclear explosion model for Moon formation (De Meijer et al., 2013) fulfills the boundary conditions and requires approximately one order of magnitude less energy than originally estimated. Hence in our view the nuclear explosion model is presently the model that best explains the formation of the Moon from predominantly terrestrial silicate material.
The past, present and future of fluorescent protein tags in anaerobic protozoan parasites
Authors: MORIN-ADELINE VICTORIA , ŠLAPETA JAN
Published: December 2015

The world health organization currently recognizes diarrhoeal diseases as a significant cause of death in children globally. Protozoan parasites such asGiardiaandEntamoebathat thrive in the oxygen-deprived environment of the human gut are common etiological agents of diarrhoea. In the urogenital tract of humans, the anaerobic protozoan parasiteTrichomonas vaginalisis notorious as the most common non-viral, sexually transmitted pathogen. Even with high medical impact, our understanding of anaerobic parasite physiology is scarce and as a result, treatment choices are limited. Fluorescent proteins (FPs) are invaluable tools as genetically encoded protein tags for advancing knowledge of cellular function. These FP tags emit fluorescent colours and once attached to a protein of interest, allow tracking of parasite proteins in the dynamic cellular space. Application of green FPs-like FPs in anaerobic protozoans is hindered by their oxygen dependency. In this review, we examine aspects of anaerobic parasite biology that clash with physio-chemical properties of FPs and limit their use as live-parasite protein tags. We expose novel FPs, such as miniSOG that do not require oxygen for signal production. The potential use of novel FPs has the opportunity to leverage the anaerobe parasitologist toolkit to that of aerobe parasitologist.
Childhood adversity and cortical thickness and surface area in a population at familial high risk of schizophrenia
Authors: Barker V. , Bois C. , Johnstone E. C. , Owens D. G. C. , Whalley H. C. , McIntosh A. M. , Lawrie S. M.
Published: December 2015

Background

There is now a well-established link between childhood adversity (CA) and schizophrenia. Similar structural abnormalities to those found in schizophrenia including alterations in grey-matter volume have also been shown in those who experience CA.

Method

We examined whether global estimates of cortical thickness or surface area were altered in those familial high-risk subjects who had been referred to a social worker or the Children's Panel compared to those who had not.

Results

We found that the cortical surface area of those who were referred to the Children's Panel was significantly smaller than those who had not been referred, but cortical thickness was not significantly altered. There was also an effect of social work referral on cortical surface area but not on thickness.

Conclusions

Cortical surface area increases post-natally more than cortical thickness. Our findings suggest that CA can influence structural changes in the brain and it is likely to have a greater impact on cortical surface area than on cortical thickness.
Dual objective motion planning subject to state constraints
Authors: Sadegh Nader
Published: December 2015

This paper presents a novel motion planning approach inspired by the Dynamic Programming (DP) applicable to multi degree of freedom robots (mobile or stationary) and autonomous vehicles. The proposed discrete–time algorithm enables a robot to reach its destination through an arbitrary obstacle field in the fewest number of time steps possible while minimizing a secondary objective function. Furthermore, the resulting optimal trajectory is guaranteed to be globally optimal while incorporating state constraints such as velocity, acceleration, and jerk limits. The optimal trajectories furnished by the algorithm may be further updated in real time to accommodate changes in the obstacle field and/or cost function. The algorithm is proven to terminate in a finite number of steps without its computational complexity increasing with the type or number of obstacles. The effectiveness of the global and replanning algorithms are demonstrated on a planar mobile robot with three degrees of freedom subject to velocity and acceleration limits. The computational complexity of the two algorithms are also compared to that of an A*–type search.
Calculating a linear-time solution to the densest-segment problem
Authors: CURTIS SHARON , MU SHIN-CHENG
Published: December 2015

The problem of finding a densest segment of a list is similar to the well-known maximum segment sum problem, but its solution is surprisingly challenging. We give a general specification of such problems, and formally develop a linear-time online solution, using a sliding-window style algorithm. The development highlights some elegant properties of densities, involving partitions that are decreasing and all right-skew.
Infiltrate and Conquer: Showing the World What Librarians Can Do
Authors: Allbon Emily
Published: December 2015

Infiltrate and Conquer … looks at how librarians might take inspiration from outside of their profession to gain greater visibility and influence within their own workplaces. The piece is a mixture of experiences: from the author, Emily Allbon, from others who have left the profession but who use those skills in other careers, and also from some librarians outside of law. The focus here is on why, and indeed how, to forge partnerships and encourage collaboration with others inside and outside of your profession. The author's Lawbore website and associated technologies will be discussed throughout the article.
A Copyright Snapshot: the Impact of New Copyright Legislation on Information Professionals
Authors: Stannard Emily
Published: December 2015

This article, written by Emily Stannard, is based on her presentation at the 2015 BIALL Annual Conference. The article discusses the recent statutory changes to the Copyright, Designs and Patents Act 1988 and reflects on the impact it has had on information professionals, especially those working within the cultural heritage and education sectors. The wording of the legislation is considered in detail with the aid of case law to provide context where necessary, particularly with reference to fair dealing provisions. Developments within the Digital Single Market of the European Union also have a significant impact on national copyright law, and it is imperative that information professionals remain informed about upcoming copyright initiatives as well as making sense of the new statutory instruments.
An exploration of the prevalence and predictors of work-related well-being among psychosocial oncology professionals: An application of the job demands–resources model
Authors: Turnell Adrienne , Rasmussen Victoria , Butow Phyllis , Juraskova Ilona , Kirsten Laura , Wiener Lori , Patenaude Andrea , Hoekstra-Weebers Josette , Grassi Luigi
Published: December 2015

Objective:

Burnout is reportedly high among oncology healthcare workers. Psychosocial oncologists may be particularly vulnerable to burnout. However, their work engagement may also be high, counteracting stress in the workplace. This study aimed to document the prevalence of both burnout and work engagement, and the predictors of both, utilizing the job demands–resources (JD–R) model, within a sample of psychosocial oncologists.

Method:

Psychosocial-oncologist (N = 417) clinicians, recruited through 10 international and national psychosocial-oncology societies, completed an online questionnaire. Measures included demographic and work characteristics, burnout (the MBI–HSS Emotional Exhaustion (EE) and Depersonalization (DP) subscales), the Utrecht Work Engagement Scale, and measures of job demands and resources.

Results:

High EE and DP was reported by 20.2 and 6.6% of participants, respectively, while 95.3% reported average to high work engagement. Lower levels of job resources and higher levels of job demands predicted greater burnout, as predicted by the JD–R model, but the predicted interaction between these characteristics and burnout was not significant. Higher levels of job resources predicted higher levels of work engagement.

Significance of results:

Burnout was surprisingly low and work engagement high in this sample. Nonetheless, one in five psychosocial oncologists have high EE. Our results suggest that both the positive (resources) and negative (demands) aspects of this work environment have an on impact burnout and engagement, offering opportunities for intervention. Theories such as the JD–R model can be useful in guiding research in this area.
The experimental power of FR900359 to study Gq-regulated biological processes
Authors: Schrage Ramona , Schmitz Anna-Lena , Gaffal Evelyn , Annala Suvi , Kehraus Stefan , Wenzel Daniela , Büllesbach Katrin M. , Bald Tobias , Inoue Asuka , Shinjo Yuji , Galandrin Ségolène , Shridhar Naveen , Hesse Michael , Grundmann Manuel , Merten Nicole , Charpentier Thomas H. , Martz Matthew , Butcher Adrian J. , Slodczyk Tanja , Armando Sylvain , Effern Maike , Namkung Yoon , Jenkins Laura , Horn Velten , Stößel Anne , Dargatz Harald , Tietze Daniel , Imhof Diana , Galés Céline , Drewke Christel , Müller Christa E. , Hölzel Michael , Milligan Graeme , Tobin Andrew B. , Gomeza Jesús , Dohlman Henrik G. , Sondek John , Harden T. Kendall , Bouvier Michel , Laporte Stéphane A. , Aoki Junken , Fleischmann Bernd K. , Mohr Klaus , König Gabriele M. , Tüting Thomas , Kostenis Evi
Published: December 2015

Despite the discovery of heterotrimeric αβγ G proteins ∼25 years ago, their selective perturbation by cell-permeable inhibitors remains a fundamental challenge. Here we report that the plant-derived depsipeptide FR900359 (FR) is ideally suited to this task. Using a multifaceted approach we systematically characterize FR as a selective inhibitor of Gq/11/14 over all other mammalian Gα isoforms and elaborate its molecular mechanism of action. We also use FR to investigate whether inhibition of Gq proteins is an effective post-receptor strategy to target oncogenic signalling, using melanoma as a model system. FR suppresses many of the hallmark features that are central to the malignancy of melanoma cells, thereby providing new opportunities for therapeutic intervention. Just as pertussis toxin is used extensively to probe and inhibit the signalling of Gi/o proteins, we anticipate that FR will at least be its equivalent for investigating the biological relevance of Gq.
Erratum: The effect of background music on episodic memory and autonomic responses: listening to emotionally touching music enhances facial memory capacity
Authors: Proverbio Alice Mado , Nasi Valentina Lozano , Arcari Laura Alessandra , De Benedetto Francesco , Guardamagna Matteo , Gazzola Martina , Zani Alberto
Published: December 2015

The aim of this study was to investigate how background auditory processing can affect other perceptual and cognitive processes as a function of stimulus content, style and emotional nature. Previous studies have offered contrasting evidence, and it has been recently shown that listening to music negatively affected concurrent mental processing in the elderly but not in young adults. To further investigate this matter, the effect of listening to music vs. listening to the sound of rain or silence was examined by administering an old/new face memory task (involving 448 unknown faces) to a group of 54 non-musician university students. Heart rate and diastolic and systolic blood pressure were measured during an explicit face study session that was followed by a memory test. The results indicated that more efficient and faster recall of faces occurred under conditions of silence or when participants were listening to emotionally touching music. Whereas auditory background (e.g., rain or joyful music) interfered with memory encoding, listening to emotionally touching music improved memory and significantly increased heart rate. It is hypothesized that touching music is able to modify the visual perception of faces by binding facial properties with auditory and emotionally charged information (music), which may therefore result in deeper memory encoding.
Origins of Cell-to-Cell Bioprocessing Diversity and Implications of the Extracellular Environment Revealed at the Single-Cell Level
Authors: Vasdekis A. E. , Silverman A. M. , Stephanopoulos G.
Published: December 2015

Bioprocess limitations imposed by microbial cell-to-cell phenotypic diversity remain poorly understood. To address this, we investigated the origins of such culture diversity during lipid production and assessed the impact of the fermentation microenvironment. We measured the single-cell lipid production dynamics in a time-invariant microfluidic environment and discovered that production is not monotonic, but rather sporadic with time. To characterize this, we introduce bioprocessing noise and identify its epigenetic origins. We linked such intracellular production fluctuations with cell-to-cell productivity diversity in culture. This unmasked the phenotypic diversity amplification by the culture microenvironment, a critical parameter in strain engineering as well as metabolic disease treatment.
An efficient planar accordion-shaped micromixer: from biochemical mixing to biological application
Authors: Cosentino Armando , Madadi Hojjat , Vergara Paola , Vecchione Raffaele , Causa Filippo , Netti Paolo Antonio
Published: December 2015

Micromixers are the key component that allow lab-on-a-chip and micro total analysis systems to reach the correct level of mixing for any given process. This paper proposes a novel, simple, passive micromixer design characterized by a planar accordion-shape geometry. The geometrical characteristics of the presented design were analyzed numerically in the range of 0.01 < Re < 100 based on the micromixer performance. The performance of the most efficient design was experimentally investigated by means of fluorescence microscopy for a range of low diffusion coefficients, 10−12 < D < 10−11 m2/s. The micromixer structure was fabricated in a simple single-step process using maskless lithography and soft lithography. The experimental results showed a very good agreement with the predicted numerical results. This micromixer design including a single serpentine unit (1-SERP) displayed an efficiency higher than 90% (mixing length = 6.4 mm) creating a pressure drop of about 500 Pa at Re = 0.1 and 60 kPa at Re = 10. A mixing efficiency of almost 100% was readily reached when three serpentine units were included (3-SERP). Finally, the potential diagnostic value of the presented microdevice was validated experimentally for Red Blood Cell (RBC) lysis.
Simvastatin suppresses breast cancer cell proliferation induced by senescent cells
Authors: Liu Su , Uppal Harpreet , Demaria Marco , Desprez Pierre-Yves , Campisi Judith , Kapahi Pankaj
Published: December 2015

Cellular senescence suppresses cancer by preventing the proliferation of damaged cells, but senescent cells can also promote cancer though the pro-inflammatory senescence-associated secretory phenotype (SASP). Simvastatin, an HMG-coA reductase inhibitor, is known to attenuate inflammation and prevent certain cancers. Here, we show that simvastatin decreases the SASP of senescent human fibroblasts by inhibiting protein prenylation, without affecting the senescent growth arrest. The Rho family GTPases Rac1 and Cdc42 were activated in senescent cells and simvastatin reduced both activities. Further, geranylgeranyl transferase, Rac1 or Cdc42 depletion reduced IL-6 secretion by senescent cells. We also show that simvastatin mitigates the effects of senescent conditioned media on breast cancer cell proliferation and endocrine resistance. Our findings identify a novel activity of simvastatin and mechanism of SASP regulation. They also suggest that senescent cells, which accumulate after radio/chemo therapy, promote endocrine resistance in breast cancer and that simvastatin might suppress this resistance.
Isotope effect on the circular dichroism spectrum of methyl α-D-glucopyranoside in aqueous solution
Authors: Kanematsu Yusuke , Kamiya Yukiko , Matsuo Koichi , Gekko Kunihiko , Kato Koichi , Tachikawa Masanori
Published: December 2015

H/D isotope effect on the circular dichroism spectrum of methyl α-D-glucopyranoside in aqueous solution has been analyzed by multicomponent density functional theory calculations using the polarizable continuum model. By comparing the computational spectra with the corresponding experimental spectrum obtained with a vacuum-ultraviolet circular dichroism spectrophotometer, it was demonstrated that the isotope effect provides insights not only into the isotopic difference of the intramolecular interactions of the solutes, but also into that of the solute–solvent intermolecular interaction.
High-Throughput Non-Contact Vitrification of Cell-Laden Droplets Based on Cell Printing
Authors: Shi Meng , Ling Kai , Yong Kar Wey , Li Yuhui , Feng Shangsheng , Zhang Xiaohui , Pingguan-Murphy Belinda , Lu Tian Jian , Xu Feng
Published: December 2015

Cryopreservation is the most promising way for long-term storage of biological samples e.g., single cells and cellular structures. Among various cryopreservation methods, vitrification is advantageous by employing high cooling rate to avoid the formation of harmful ice crystals in cells. Most existing vitrification methods adopt direct contact of cells with liquid nitrogen to obtain high cooling rates, which however causes the potential contamination and difficult cell collection. To address these limitations, we developed a non-contact vitrification device based on an ultra-thin freezing film to achieve high cooling/warming rate and avoid direct contact between cells and liquid nitrogen. A high-throughput cell printer was employed to rapidly generate uniform cell-laden microdroplets into the device, where the microdroplets were hung on one side of the film and then vitrified by pouring the liquid nitrogen onto the other side via boiling heat transfer. Through theoretical and experimental studies on vitrification processes, we demonstrated that our device offers a high cooling/warming rate for vitrification of the NIH 3T3 cells and human adipose-derived stem cells (hASCs) with maintained cell viability and differentiation potential. This non-contact vitrification device provides a novel and effective way to cryopreserve cells at high throughput and avoid the contamination and collection problems.
RNAi mediated inhibition of viroid infection in transgenic plants expressing viroid-specific small RNAs derived from various functional domains
Authors: Adkar-Purushothama Charith Raj , Kasai Atsushi , Sugawara Kohei , Yamamoto Hideki , Yamazaki Yuto , He Ying-Hong , Takada Nobuyuki , Goto Hideki , Shindo Sahori , Harada Takeo , Sano Teruo
Published: December 2015

Previous attempts to develop RNAi-mediated viroid-resistant transgenic plants using nearly full-length Potato spindle tuber viroid (PSTVd) hairpin RNA (hpRNA) were successful; however unusual phenotypes resembling viroid infection occurred. Therefore, in the present work, transgenic Nicotiana benthamiana lines expressing both partial and truncated versions of PSTVd hpRNA were developed. Specifically, seven partial or truncated versions of PSTVd sequences were selected according to the hotspots of both PSTVd-sRNAs and functional domains of the PSTVd. A total of 21 transgenic lines Nicotiana benthamiana were developed under the control of either the CaMV-35S or the CoYMV promoters. All of the transgenic lines established here were monitored for the induction of phenotypic changes, for PSTVd-sRNA expression and for the resistance against PSTVd infection. Additionally, this study demonstrates the use of inverted repeat construct sequences as short as 26- to -49 nucleotides for both the efficient expression of the PSTVd-sRNA and the inhibition of PSTVd infection.
Suspended sediments limit coral sperm availability
Authors: Ricardo Gerard F. , Jones Ross J. , Clode Peta L. , Humanes Adriana , Negri Andrew P.
Published: December 2015

Suspended sediment from dredging activities and natural resuspension events represent a risk to the reproductive processes of coral and therefore the ongoing maintenance of reefal populations. To investigate the underlying mechanisms that could reduce the fertilisation success in turbid water, we conducted several experiments exposing gametes of the coralsAcropora tenuisandA. milleporato two sediment types. Sperm limitation was identified in the presence of siliciclastic sediment (230 and ~700 mg L−1), with 2–37 fold more sperm required to achieve maximum fertilisation rates, when compared with sediment-free treatments. This effect was more pronounced at sub-optimum sperm concentrations. Considerable (>45%) decreases in sperm concentration at the water’s surface was recorded in the presence of siliciclastic sediment and a >20% decrease for carbonate sediment. Electron microscopy then confirmed sediment entangled sperm and we propose entrapment and sinking is the primary mechanism reducing sperm available to the egg. Longer exposure to suspended sediments and gamete aging further decreased fertilisation success when compared with a shorter exposure. Collectively, these findings demonstrate that high concentrations of suspended sediments effectively remove sperm from the water’s surface during coral spawning events, reducing the window for fertilisation with potential subsequent flow-on effects for recruitment.
Cardioprotective effects of fatty acid amide hydrolase inhibitor URB694, in a rodent model of trait anxiety
Authors: Carnevali Luca , Vacondio Federica , Rossi Stefano , Macchi Emilio , Spadoni Gilberto , Bedini Annalida , Neumann Inga D. , Rivara Silvia , Mor Marco , Sgoifo Andrea
Published: December 2015

In humans, chronic anxiety represents an independent risk factor for cardiac arrhythmias and sudden death. Here we evaluate in male Wistar rats bred for high (HAB) and low (LAB) anxiety-related behavior, as well as non-selected (NAB) animals, the relationship between trait anxiety and cardiac electrical instability and investigate whether pharmacological augmentation of endocannabinoid anandamide-mediated signaling exerts anxiolytic-like and cardioprotective effects. HAB rats displayed (i) a higher incidence of ventricular tachyarrhythmias induced by isoproterenol and (ii) a larger spatial dispersion of ventricular refractoriness assessed by means of an epicardial mapping protocol. In HAB rats, acute pharmacological inhibition of the anandamide-degrading enzyme, fatty acid amide hydrolase (FAAH), with URB694 (0.3 mg/kg), (i) decreased anxiety-like behavior in the elevated plus maze, (ii) increased anandamide levels in the heart, (iii) reduced isoproterenol-induced occurrence of ventricular tachyarrhythmias and (iv) corrected alterations of ventricular refractoriness. The anti-arrhythmic effect of URB694 was prevented by pharmacological blockade of the cannabinoid type 1 (CB1), but not of the CB2, receptor. These findings suggest that URB694 exerts anxiolytic-like and cardioprotective effects in HAB rats, the latter via anandamide-mediated activation of CB1 receptors. Thus, pharmacological inhibition of FAAH might be a viable pharmacological strategy for the treatment of anxiety-related cardiac dysfunction.
Plant stoichiometric responses to elevated CO2 vary with nitrogen and phosphorus inputs: Evidence from a global-scale meta-analysis
Authors: Huang Wenjuan , Houlton Benjamin Z. , Marklein Alison R. , Liu Juxiu , Zhou Guoyi
Published: December 2015

Rising levels of atmospheric CO2 have been implicated in changes in the nitrogen (N) and phosphorus (P) content of terrestrial vegetation; however, questions remain over the role of C, N and P interactions in driving plant nutrient stoichiometry, particularly whether N and P additions alter vegetation responses to CO2 enrichment singly. Here we use meta-analysis of 46 published studies to investigate the response of plant N and P to elevated CO2 alone and in combination with nutrient (N and P) additions across temperate vs. tropical biomes. Elevated CO2 reduces plant N concentrations more than plant P concentrations in total biomass pools, resulting in a significant decline in vegetation N/P. However, elevated CO2 treatments in combination with N additions increase plant P concentrations, whereas P additions have no statistical effect on plant N concentrations under CO2 enrichment. These results point to compensatory but asymmetrical interactions between N, P and CO2; that changes in N rapidly alter the availability of P, but not the converse, in response to increased CO2. Our finding implies widespread N limitation with increasing atmospheric CO2 concentrations alone. We also suggest that increased anthropogenic N deposition inputs could enhance plant N and P in a progressively CO2-enriched biosphere.
MicroRNA 19a replacement partially rescues fin and cardiac defects in zebrafish model of Holt Oram syndrome
Authors: Chiavacci Elena , D’Aurizio Romina , Guzzolino Elena , Russo Francesco , Baumgart Mario , Groth Marco , Mariani Laura , D’Onofrio Mara , Arisi Ivan , Pellegrini Marco , Cellerino Alessandro , Cremisi Federico , Pitto Letizia
Published: December 2015

Holt-Oram Syndrome (HOS) is an autosomal dominant heart-hand syndrome caused by mutations in the TBX5 gene, a transcription factor capable of regulating hundreds of cardiac-specific genes through complex transcriptional networks. Here we show that, in zebrafish, modulation of a single miRNA is sufficient to rescue the morphogenetic defects generated by HOS. The analysis of miRNA-seq profiling revealed a decreased expression of miR-19a in Tbx5-depleted zebrafish embryos compared to the wild type. We revealed that the transcription of the miR-17-92 cluster, which harbors miR-19a, is induced by Tbx5 and that a defined dosage of miR-19a is essential for the correct development of the heart. Importantly, we highlighted that miR-19a replacement is able to rescue cardiac and pectoral fin defects and to increase the viability of HOS zebrafish embryos. We further observed that miR-19a replacement shifts the global gene expression profile of HOS-like zebrafish embryos towards the wild type condition, confirming the ability of miR-19a to rescue the Tbx5 phenotype. In conclusion our data demonstrate the importance of Tbx5/miR-19a regulatory circuit in heart development and provide a proof of principle that morphogenetic defects associated with HOS can be rescued by transient miRNA modulation.
The interplay of the Notch signaling in hepatic stellate cells and macrophages determines the fate of liver fibrogenesis
Authors: Bansal Ruchi , van Baarlen Joop , Storm Gert , Prakash Jai
Published: December 2015

Hepatic stellate cells (HSCs) known as “master producers” and macrophages as “master regulators”, are the key cell types that strongly contribute to the progression of liver fibrosis. Since Notch signaling regulates multiple cellular processes, we aimed to study the role of Notch signaling in HSCs differentiation and macrophages polarization and to evaluate its implication in liver fibrogenesis. Notch pathway components were found to be significantly upregulated in TGFβ-activated HSCs, inflammatory M1 macrophages and in mouse and human fibrotic livers. Interestingly, inhibition of Notch using a selective γ-secretase inhibitor, Avagacestat, significantly inhibited TGFβ-induced HSC activation and contractility and suppressed M1 macrophages. Additionally, Avagacestat inhibited M1 driven-fibroblasts activation and fibroblasts-driven M1 polarization (nitric oxide release) in fibroblasts and macrophages co-culture and conditioned medium studies. In vivo, post-disease treatment with Avagacestat significantly attenuated fibrogenesis in CCl4-induced liver fibrosis mouse model. These effects were attributed to the reduction in HSCs activation and inhibition of inflammatory M1 macrophages and upregulation of suppressive M2 macrophages. These findings suggest that Notch signaling plays a crucial role in HSC activation and M1/M2 polarization of macrophages in liver fibrosis. These results provide new insights for the development of novel therapies against liver fibrosis through modulation of Notch signaling.
Comparison of the depolarization response of human mesenchymal stem cells from different donors
Authors: Sundelacruz Sarah , Levin Michael , Kaplan David L.
Published: December 2015

Bioelectric signaling is currently being explored as a novel regulator of cell processes in non-excitable cells. In particular, stem cells have demonstrated increasing evidence of electrophysiology-mediated regulation of stemness acquisition, proliferation, differentiation and migration. However, in light of many reports of primary stem cell heterogeneity, it is important to characterize the variability of stem cell response to biophysical manipulations in order to assess the utility of bioelectric modulation as a universal strategy for stem cell control. In this work, human mesenchymal stem cells (hMSCs) from five donors were evaluated for their response to membrane potential (Vmem) depolarization. We compared the inter-donor variability of their osteogenic and adipogenic differentiation potential, as well as their ability to maintain a differentiated phenotype after induction. We identified the markers that responded most consistently across donors and found that calcium deposition and gene expression of bone sialoprotein, lipoprotein lipase and fatty acid binding protein 4 are the preferred markers for assessing differentiation response to Vmemdepolarization. We also note that since there exists variability even among some of these markers, these assays should be performed on any newly acquired hMSC population if their bioelectric properties are to be studied further.
Detection of fatty acid-binding protein 5 and small proline-rich protein 3 for forensic vaginal fluid identification by ELISA
Authors: Igoh Akihisa , Akutsu Tomoko , Doi Yusuke
Published: December 2015

Vaginal fluid identification is often required for forensic investigation of sexual assault cases.
Hydrophilic interaction liquid chromatography for separation and determination of pyrrolidinium ionic liquid cations
Authors: Guan Chao , Yu Hong
Published: December 2015

The separation and detection of pyrrolidinium cations by hydrophilic interaction liquid chromatography with indirect ultraviolet detection.
Confinement effects on the shape and composition of bimetallic nano-objects in carbon nanotubes
Authors: Li X. , Hungria T. , Garcia Marcelot C. , Axet M. R. , Fazzini P.-F. , Tan R. P. , Serp P. , Soulantica K.
Published: December 2015

The shape and the composition of bimetallic alloys prepared by in situ reduction of molecular precursors depends on the carbon nanotube diameter.
Organocatalytic enantio- and diastereoselective synthesis of 3,5-disubstituted prolines
Authors: Riaño Iker , Díaz Estibaliz , Uria Uxue , Reyes Efraím , Carrillo Luisa , Vicario Jose L.
Published: December 2015

The asymmetric synthesis of substituted pyrrolidines has been accomplished using a novel organocatalytic cyclization reaction promoted by aCinchonaalkaloid base primary amine.
Expedient synthesis of new cinnoline diones by Ru-catalyzed regioselective unexpected deoxygenation-oxidative annulation of propargyl alcohols with phthalazinones and pyridazinones
Authors: Rajkumar Subramani , Antony Savarimuthu S. , Senthil Kumaran Rajendran , Nagaraja C. M. , Gandhi Thirumanavelan
Published: December 2015

Ruthenium-catalyzed simple, cascade and one-pot synthesis of cinnoline-fused diones has been carried out by the C–H activation of phthalazinones/pyridazinones.
Target-selective photo-degradation of AFP-L3 and selective photo-cytotoxicity against HuH-7 hepatocarcinoma cells using an anthraquinone–PhoSL hybrid
Authors: Okuyama Mai , Ueno Haruna , Kobayashi Yuka , Kawagishi Hirokazu , Takahashi Daisuke , Toshima Kazunobu
Published: December 2015

A purposefully-designed anthraquinone–Pholiota squarrosa lectin (PhoSL) hybrid effectively degraded α-fetoprotein-L3 (AFP-L3) associated with liver cancer.
Optical and surface enhanced Raman scattering properties of Au nanoparticles embedded in and located on a carbonaceous matrix
Authors: Prakash Jai , Kumar Vinod , Kroon R. E. , Asokan K. , Rigato V. , Chae K. H. , Gautam S. , Swart H. C.
Published: December 2015

Au nanoparticles (NPs) on the surface and embedded in a matrix have been the subject of studies dealing with a variety of spectroscopic and sensing applications.
Controllable defluorination of fluorinated graphene and weakening of C–F bonding under the action of nucleophilic dipolar solvent
Authors: Wang Xu , Wang Weimiao , Liu Yang , Ren Mengmeng , Xiao Huining , Liu Xiangyang
Published: December 2015

Some dipolar solvents promote the reduction of fluorinated grapheee and the weakening of strong covalent C–F bonding, which leads to a series of changes in the structure and properties of fluorinated graphene.
Correction: Quantifying transient interactions between amide groups and the guanidinium cation
Authors: Balos V. , Bonn M. , Hunger J.
Published: December 2015

Correction for ‘Quantifying transient interactions between amide groups and the guanidinium cation’ by V. Balos et al., Phys. Chem. Chem. Phys., 2015, 17, 28539–28543.
Unique selectivity reversal in Am3+–Eu3+ extraction in a tripodal TREN-based diglycolamide in ionic liquid: extraction, luminescence, complexation and structural studies
Authors: Leoncini Andrea , Mohapatra Prasanta K. , Bhattacharyya Arunasis , Raut Dhaval R. , Sengupta Arijit , Verma Parveen K. , Tiwari Nidhi , Bhattacharyya Dibyendu , Jha Sambhunath , Wouda Anna M. , Huskens Jurriaan , Verboom Willem
Published: December 2015

A unique selectivity reversal in metal ion extraction was seen in DGA-TREN vis-à-vis T-DGA.