bluuebunny/crossref_metadata_2025 huggingface dataset:
Exogenous fatty acids alter phospholipid composition, membrane permeability, capacity for biofilm formation, and antimicrobial peptide susceptibility in Klebsiella pneumoniae
Authors: Hobby Chelsea R. , Herndon Joshua L. , Morrow Colton A. , Peters Rachel E. , Symes Steven J. K. , Giles David K.
Published: April 2018

Klebsiella pneumoniae represents a major threat to human health due to a combination of its nosocomial emergence and a propensity for acquiring antibiotic resistance. Dissemination of the bacteria from its native intestinal location creates severe, complicated infections that are particularly problematic in healthcare settings. Thus, there is an urgency for identifying novel treatment regimens as the incidence of highly antibiotic‐resistant bacteria rises. Recent findings have highlighted the ability of some Gram‐negative bacteria to utilize exogenous fatty acids in ways that modify membrane phospholipids and influence virulence phenotypes, such as biofilm formation and antibiotic resistance. This study explores the ability of K. pneumoniae to assimilate and respond to exogenous fatty acids. The combination of thin‐layer chromatography liquid chromatography‐mass spectrometry confirmed adoption of numerous exogenous polyunsaturated fatty acids (PUFAs) into the phospholipid species of K. pneumoniae. Membrane permeability was variably affected as determined by two dye uptake assays. Furthermore, the availability of many PUFAs lowered the MICs to the antimicrobial peptides polymyxin B and colistin. Biofilm formation was significantly affected depending upon the supplemented fatty acid.
Evaluation of smartphone‐based testing to generate exploratory outcome measures in a phase 1 Parkinson's disease clinical trial
Authors: Lipsmeier Florian , Taylor Kirsten I. , Kilchenmann Timothy , Wolf Detlef , Scotland Alf , Schjodt‐Eriksen Jens , Cheng Wei‐Yi , Fernandez‐Garcia Ignacio , Siebourg‐Polster Juliane , Jin Liping , Soto Jay , Verselis Lynne , Boess Frank , Koller Martin , Grundman Michael , Monsch Andreas U. , Postuma Ronald B. , Ghosh Anirvan , Kremer Thomas , Czech Christian , Gossens Christian , Lindemann Michael
Published: April 2018

Background: Ubiquitous digital technologies such as smartphone sensors promise to fundamentally change biomedical research and treatment monitoring in neurological diseases such as PD, creating a new domain of digital biomarkers.

Objectives: The present study assessed the feasibility, reliability, and validity of smartphone‐based digital biomarkers of PD in a clinical trial setting.

Methods: During a 6‐month, phase 1b clinical trial with 44 Parkinson participants, and an independent, 45‐day study in 35 age‐matched healthy controls, participants completed six daily motor active tests (sustained phonation, rest tremor, postural tremor, finger‐tapping, balance, and gait), then carried the smartphone during the day (passive monitoring), enabling assessment of, for example, time spent walking and sit‐to‐stand transitions by gyroscopic and accelerometer data.

Results: Adherence was acceptable: Patients completed active testing on average 3.5 of 7 times/week. Sensor‐based features showed moderate‐to‐excellent test‐retest reliability (average intraclass correlation coefficient = 0.84). All active and passive features significantly differentiated PD from controls with P < 0.005. All active test features except sustained phonation were significantly related to corresponding International Parkinson and Movement Disorder Society–Sponsored UPRDS clinical severity ratings. On passive monitoring, time spent walking had a significant (P = 0.005) relationship with average postural instability and gait disturbance scores. Of note, for all smartphone active and passive features except postural tremor, the monitoring procedure detected abnormalities even in those Parkinson participants scored as having no signs in the corresponding International Parkinson and Movement Disorder Society–Sponsored UPRDS items at the site visit.

Conclusions: These findings demonstrate the feasibility of smartphone‐based digital biomarkers and indicate that smartphone‐sensor technologies provide reliable, valid, clinically meaningful, and highly sensitive phenotypic data in Parkinson's disease. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Protein molecular modeling techniques investigating novel TAB2 variant R347X causing cardiomyopathy and congenital heart defects in multigenerational family
Authors: Caulfield Thomas R. , Richter John E. , Brown Emily E. , Mohammad Ahmed N. , Judge Daniel P. , Atwal Paldeep S.
Published: April 2018

Background

Haploinsufficiency of TAB2 is known to cause congenital heart defects and cardiomyopathy due to its important roles in cardiovascular tissue, both during development and through adult life. We report a sibling pair displaying adult‐onset cardiomyopathy, hypermobility, and mild myopia. Our proband, a 39‐year‐old male, presents only with the above symptoms, while his 36‐year‐old sister was also notable for a ventricular septal defect in her infancy.

Methods

Whole‐exome sequencing was utilized to identify the molecular basis of the phenotype found in two siblings. A molecular modeling technique that takes advantage of conformational sampling advances (Maxwell's demon molecular dynamics and Monte Carlo) were used to make a model of the mutant variant for comparative analytics to the wild‐type.

Results

Exome sequencing revealed a novel, heterogeneous pathogenic variant in TAB2, c.1039 C>T (p.R347X), that was present in both individuals. This pathogenic variant removes just over half the residues from the TAB2 protein and severely impacts its functional ability, which we describe in detail.

Conclusions

Analysis of the proband's family showed a history of cardiomyopathy, but no congenital heart defects or connective tissue disease. We highlight the heterogeneity in phenotype of TAB2 pathogenic variants and confirm the pathogenicity of this new variant through neoteric protein modeling techniques.
On the global dynamic behaviour for a generalized haematopoiesis model with almost periodic coefficients and oscillating circulation loss rate
Authors: Amster Pablo , Balderrama Rocío
Published: April 2018

A generalized non‐linear nonautonomous model for the haematopoiesis (cell production) with several delays and an oscillating circulation loss rate is studied. We prove a fixed point theorem in abstract cones, from which different results on existence and uniqueness of positive almost periodic solutions are deduced. Moreover, some criteria are given to guarantee that the obtained positive almost periodic solution is globally exponentially stable.
The well‐posedness of the double‐diffusive convection system in a bounded domain
Authors: Chen Fei , Guo Boling , Zeng Lan
Published: April 2018

In this paper, we consider the well‐posedness of the initial and boundary value problem for the double‐diffusive convection system in a bounded domain
. We first prove the local existence of the unique strong solution with large initial data in
and then extend it to a global one provided the L2 norm of the initial data is small.
On the numerical solution of stochastic quadratic integral equations via operational matrix method
Authors: Mirzaee Farshid , Samadyar Nasrin
Published: April 2018

In this paper, stochastic operational matrix of integration based on delta functions is applied to obtain the numerical solution of linear and nonlinear stochastic quadratic integral equations (SQIEs) that appear in modelling of many real problems. An important advantage of this method is that it dose not need any integration to compute the constant coefficients. Also, this method can be utilized to solve both linear and nonlinear problems. By using stochastic operational matrix of integration together collocation points, solving linear and nonlinear SQIEs converts to solve a nonlinear system of algebraic equations, which can be solved by using Newton's numerical method. Moreover, the error analysis is established by using some theorems. Also, it is proved that the rate of convergence of the suggested method is O(h2). Finally, this method is applied to solve some illustrative examples including linear and nonlinear SQIEs. Numerical experiments confirm the good accuracy and efficiency of the proposed method.
On some dynamic inequalities of Steffensen type on time scales
Authors: Abdeldaim A. , El‐Deeb A. A. , Agarwal Praveen , El‐Sennary H. A.
Published: April 2018

In the present article, we investigate some new inequalities of Steffensen type on an arbitrary time scale using the diamond‐α dynamic integrals, which are defined as a linear combination of the delta and nabla integrals. The obtained inequalities extend some known dynamic inequalities on time scales and unify and extend some continuous inequalities and their discrete analogues.
Impact of miR‐140 Deficiency on Non‐Alcoholic Fatty Liver Disease
Authors: Wolfson Benjamin , Lo Pang‐Kuo , Yao Yuan , Li Linhao , Wang Hongbing , Zhou Qun
Published: April 2018

Scope

We have previously shown that loss of miR‐140 has a pro‐fibrotic effect in the mammary gland. This study aims to investigate whether miR‐140 loss and obesity act synergistically to promote non‐alcoholic fatty liver disease (NAFLD), and to identify the underlying mechanisms.

Methods and Results

Liver tissues were isolated from lean‐fat‐diet and high‐fat‐diet fed wild‐type and miR‐140 knockout mice. Using molecular staining and immunohistochemistry techniques, increased development of NAFLD and fibrotic indicators in miR‐140 knockout mice were identified. Utilizing an in vitro model system, miR‐140 was demonstrated to target TLR‐4, and miR‐140 overexpression was shown to be sufficient to inhibit palmitic acid signaling through the TLR‐4/NFκB pathway.

Conclusion

These findings demonstrate that loss of miR‐140 results in increased expression of TLR‐4, sensitizing cells to palmitic acid signaling and in increased inflammatory activity through the TLR4/NFκB pathway. This signaling axis promotes NAFLD development in a high‐fat diet context and indicates the potential utility of miR‐140 rescue as a therapeutic strategy in NAFLD.
The Leiden Family Lab study on Social Anxiety Disorder: A multiplex, multigenerational family study on neurocognitive endophenotypes
Authors: Bas‐Hoogendam Janna Marie , Harrewijn Anita , Tissier Renaud L.M. , van der Molen Melle J.W. , van Steenbergen Henk , van Vliet Irene M. , Reichart Catrien G. , Houwing‐Duistermaat Jeanine J. , Slagboom P. Eline , van der Wee Nic J.A. , Westenberg P. Michiel
Published: April 2018

Abstract

Objectives

Social anxiety disorder (SAD) is a serious and prevalent psychiatric condition, with a heritable component. However, little is known about the characteristics that are associated with the genetic component of SAD, the so‐called “endophenotypes”. These endophenotypes could advance our insight in the genetic susceptibility to SAD, as they are on the pathway from genotype to phenotype. The Leiden Family Lab study on Social Anxiety Disorder (LFLSAD) is the first multiplex, multigenerational study aimed to identify neurocognitive endophenotypes of social anxiety.

Methods

The LFLSAD is characterized by a multidisciplinary approach and encompasses a variety of measurements, including a clinical interview, functional and structural magnetic resonance imaging and an electroencephalography experiment. Participants are family members from 2 generations, from families genetically enriched for SAD.

Results

The sample (n = 132 participants, from 9 families) was characterized by a high prevalence of SAD, in both generations (prevalence (sub)clinical SAD: 38.3%). Furthermore, (sub)clinical SAD was positively related to self‐reported social anxiety, fear of negative evaluation, trait anxiety, behavioral inhibition, negative affect, and the level of depressive symptoms.

Conclusions

By the multidimensional character of the measurements and thorough characterization of the sample, the LFLSAD offers unique opportunities to investigate candidate neurocognitive endophenotypes of SAD.
Therapeutic experience with hepatoblastoma associated with trisomy 18
Authors: Inoue Akiko , Suzuki Ryo , Urabe Keisuke , Kawamura Yutaro , Masuda Midori , Kishi Kanta , Takitani Kimitaka , Katayama Hiroshi , Tomiyama Hideki , Hayashi Michihiro , Nemoto Shintaro , Uchiyama Kazuhisa , Tamai Hiroshi
Published: April 2018

Trisomy 18 is often fatal, but patients with this disease can now have longer survival due to proactive treatment intervention. However, hepatoblastomas may develop in these patients. In this study, we report four cases of hepatoblastoma associated with trisomy 18. All of the patients had congenital heart disease and three had undergone intracardiac surgical repair. Tumor growth was relatively slow in all cases, and there were no problems with chemotherapy tolerability and surgical resection. Three of the patients are currently disease‐free and the fourth is alive with remaining of the tumor. These cases suggest that combined chemotherapy and surgical resection may be an option to treat hepatoblastoma associated with trisomy 18 when cardiac pulmonary function is relatively stable.
Improving the processibility and mechanical properties of poly(lactic acid)/linear low‐density polyethylene/paraffin wax blends by subcritical gas‐assisted processing
Authors: Chen Yann‐Jiun , Yu Emily , Ellingham Thomas , Chung Chunhui , Turng Lih‐Sheng
Published: April 2018

Previous studies have shown that paraffin wax (PW) is capable of improving the ductility and fluidity of poly(lactic acid) (PLA) matrices. However, PLA and PW are immiscible, thus the low melting temperature of PW (at around 55°C) will pose some processing difficulties and/or practical application limitations on PLA/PW blends. Since linear low‐density polyethylene (LLDPE) and PW exhibited miscibility at a 90%/10% weight ratio and a melting temperature of 123°C, LLDPE was added to the PLA/PW blends in order to increase their thermal stability, processability, and elongation‐at‐break. The blends were prepared by a twin‐screw extruder using two different melt compounding processes: conventional melt compounding extrusion and subcritical gas‐assisted processing. Then, neat PLA, LLDPE, and the blends were injection molded into tensile bars for evaluation. To observe the effects of the two melt compounding processes, the thermal properties, mechanical properties, and phase morphologies of the various blends were characterized. The physical foaming agent (nitrogen, N2) used in the subcritical gas‐assisted processing process also plasticized the melt, thereby reducing the likelihood of thermal degradation and improving the mixing performance. POLYM. ENG. SCI., 58:2320–2331, 2018. © 2018 Society of Plastics Engineers
Durable pressure filtration membranes based on polyaniline–polyimide P84 blends
Authors: Yusoff Izzati Izni , Rohani Rosiah , Khairul Zaman Nadiah , Junaidi Mohd Usman Mohd , Mohammad Abdul Wahab , Zainal Zamardina
Published: April 2018

A pressure filtration membrane from conducting polymer polyaniline (PANI) is known to possess low mechanical strength and thermal stability. Therefore, it is believed that the properties of the membrane can be enhanced by blending PANI with a conventional polymer like polyimide (PI), which possesses high mechanical strength and thermal stability. A thermal analysis revealed that polymer chain of blend membranes started to break beyond the melting temperature of pure PANI membrane indicating that the addition of PI hindered the degradation of PANI and thus slowed down the decomposition process. Mechanical tests further showed that PANI/PI membrane had a tensile strength that was 60% higher than pure PANI membrane. Furthermore, the surface hydrophilicity and negativity of the blend membrane increased as it was doped in acid, thereby reflecting the exploitation of advantages of both polymers. Rejection at various molecular ranges of PEGs showed that PANI/PI membrane was initially in the ultrafiltration (UF) range, but later fell into the nanofiltration (NF) range when an acid dopant was introduced to the membrane. According to the long‐term filtration performance, the PANI/PI membrane was able to sustain a rejection of up to 99% in Congo red solution with just a slight reduction in flux. POLYM. ENG. SCI., 59:E82–E92, 2019. © 2018 Society of Plastics Engineers
Polyurethane/doxorubicin nanoparticles based on electrostatic interactions as pH‐sensitive drug delivery carriers
Authors: Huang Dengcheng , Zhou Yu , Xiang Yuan , Shu Meijie , Chen Hongxiang , Yang Bing , Liao Xinghua
Published: April 2018

In order to obtain a pH‐sensitive delivery carrier for doxorubicin (DOX), DOX‐loaded polyurethane (PU·DOX) nanoparticles were readily prepared in water by electrostatic interactions between amphiphilic polyurethane with carboxyl pendent groups (PU‐COOH) and doxorubicin hydrochloride (DOX·HCl). The structures of the products obtained were characterized by Fourier transform infrared spectroscopy, 1H NMR spectroscopy, gel permeation chromatography, UV–visible spectroscopy, dynamic light scattering and transmission electron microscopy. The average hydrodynamic size of the PU·DOX nanoparticles was around 182 nm with negative surface charge (−1.1 mV) and a spherical or rodlike shape. PU·DOX nanoparticles had a higher drug‐loading content of 14.1 wt%. The in vitro drug release properties of PU·DOX nanoparticles were investigated at pH 4.0, 5.0 and 7.4, respectively. PU·DOX nanoparticles exhibited a good pH‐sensitive drug release property, but there was almost no release of DOX from PU·DOX nanoparticles at pH 7.4. The in vitro cellular uptake assay and the Cell Counting Kit‐8 assay demonstrated that PU·DOX nanoparticles had a higher level of cellular internalization and higher inhibitory effects on the proliferation of human breast cancer (MCF‐7) cells than pure DOX. The enhancement of the inhibition effects resulted from increasing apoptosis‐inducing effects on MCF‐7 cells, which was related to the enhancement of Bax expression and the reduction of Bcl‐2 expression confirmed by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay, real‐time polymerase chain reaction (PCR) assay and western blot assay. © 2018 Society of Chemical Industry
Psychosexual development and satisfaction with timing of developmental milestones among adult survivors of childhood cancer
Authors: Lehmann Vicky , Keim Madelaine C. , Ferrante Amanda C. , Olshefski Randal S. , Gerhardt Cynthia A.
Published: April 2018

Objective

To extend the limited research on psychosexual development among childhood cancer survivors, by not only focusing on the prevalence and age of milestone attainment, but also survivors' attitudes toward the timing of reaching such milestones.

Methods

Adult survivors of childhood cancer (N = 90; Mage = 29.8, SD = 5.2), recruited from a US pediatric institution, completed online surveys indicating whether they had reached 5 milestones of psychosexual development (ie, first kiss, first boy‐/girlfriend, first physical intimacy, sexual debut, first time in love), age at attainment, and perceptions about the timing (ie, right time, wished it had happened earlier, wished they had waited).

Results

Almost all survivors had reached each milestone (≥90%), except for sexual debut (83.3%). Survivors reported their first kiss as the earliest milestone at age 14.6 (N = 82, 92%) and falling in love as the latest milestone at age 18.8 (N = 80; 90%). This timing did not differ by sex/cancer‐specific factors. Most survivors (~60%) felt they reached each milestone at the right time. Compared with US normative data, both male and female survivors were less likely to have experienced their sexual debut and were approximately 1.5 years older at sexual debut. Nevertheless, 59% of survivors felt that this timing was right and 31% wished they had waited longer.

Conclusions

This is the first study to demonstrate that although childhood cancer survivors may delay some aspects of psychosexual development, most are satisfied with this timing. Research and clinical practice should emphasize survivors' perceptions/satisfaction toward psychosexual development rather than focusing only on normative milestone attainment.
Tidal breath eNO measurements in a cohort of unsedated hospitalized neonates—A method validation
Authors: Schmidt Birgitte J. , Reim Pauline S. , Jensen Andreas K. , Albertsen Per , Greisen Gorm , Jørgensen Inger M.
Published: April 2018

Aim

Exhaled Nitric oxide (eNO) is an inflammatory marker. In 2002 Hall et al. [J Appl Physiol. 92:59‐66] established an infant eNO measurement method, fulfilling four criteria of feasibility: simple, non‐invasive, without impact on the natural breathing pattern, and accounting for flow by NO output (V'NO). Although tidal breathing is accepted as an eNO measurement method in uncooperative patients, it is seldom used outside research labs. The variability and lack of validated methods have restrained from exploring the area in preterm and term neonates the last years. This study aimed to validate clinically feasible longitudinal online tidal eNO and V'NO in a real‐life birth cohort of un‐sedated, hospitalized preterm, and term neonates.

Method

We included 149 newborns, GA 28‐42 weeks. Each scheduled for six repeated, non‐invasive, on‐line eNO measurements with Ecomedics CLD 88sp and NO‐free air. We used three 60‐second‐eNO measurements. The method was adapted to fit preterm and term neonates with unstable respiration, without excluding sighs and surrounding breaths.

Result

Protocol measurements with a maximum mutual difference of 1 ppb succeeded in 85‐99%, increasing with postnatal age. We performed mixed model analyses in three hierarchical measurement levels. Despite the irregular breathing of newborns, the predictions of individual eNO levels in the average infant was a 0.05 SD. Exhaled NO was flow‐dependent (P = 0.028); V'NO but not eNO was associated with preterm birth (P < 0.001) and >24 h CPAP treatment (P = 0.0316).

Conclusion

We validated clinically, non‐invasive, online eNO measurements in neonates. The method was well tolerated and exhibited low subject‐specific‐prediction‐variance and high success rates.
Surface enhanced Raman spectroscopy distinguishes amyloid Β‐protein isoforms and conformational states
Authors: Yu Xinke , Hayden Eric Y. , Xia Ming , Liang Owen , Cheah Lisa , Teplow David B. , Xie Ya‐Hong
Published: April 2018

Amyloid β‐protein (Aβ) self‐association is one process linked to the development of Alzheimer's disease (AD). Aβ peptides, including its most abundant forms, Aβ40 and Aβ42, are associated with the two predominant neuropathologic findings in AD, vascular and parenchymal amyloidosis, respectively. Efforts to develop therapies for AD often have focused on understanding and controlling the assembly of these two peptides. An obligate step in these efforts is the monitoring of assembly state. We show here that surface‐enhanced Raman spectroscopy (SERS) coupled with principal component analysis (PCA) readily distinguishes Aβ40 and Aβ42. We show further, through comparison of assembly dependent changes in secondary structure and morphology, that the SERS/PCA approach unambiguously differentiates closely related assembly stages not readily differentiable by circular dichroism spectroscopy, electron microscopy, or other techniques. The high discriminating power of SERS/PCA is based on the rich structural information present in its spectra, which comprises not only on interatomic resonances between covalently associated atoms and hydrogen bond interactions important in controlling secondary structure, but effects of protein orientation relative to the substrate surface. Coupled with the label‐free, single molecule sensitivity of SERS, the approach should prove useful for determining structure activity relationships, suggesting target sites for drug development, and for testing the effects of such drugs on the assembly process. The approach also could be of value in other systems in which assembly dependent changes in protein structure correlate with the formation of toxic peptide assemblies.
Labeling membrane receptors with lectins and evaluation of the midgut histochemistry of Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) populations with different levels of susceptibility to formulated Bt
Authors: Oliveira Andresa CB , Wanderley‐Teixeira Valeria , Silva Cristiane TS , Teixeira Álvaro AC , Siqueira Herbert AA , Cruz Glauciane S , Neto Clovis J C Lapa , Lima Amanda LR , Correia Maria TS
Published: April 2018

BACKGROUND

Studies show that insects can adapt to the toxins of Bacillus thuringiensis under field and laboratory conditions through the development of resistance to the bacterium and its formulations. This has been demonstrated in the failure to control Tuta absoluta populations in Brazil. This study evaluated membrane receptors using peroxidase‐labeled lectins and the midgut histochemistry of T. absoluta populations to assess susceptibility to the insecticides Bt fomulations. The histochemistry analysis used Periodic Acid–Schiff for glycogen and Ponceau Xylidine for total proteins. The presence of glucose/mannose and N‐acetylgalactosamine (GalNAc) was analyzed using specific lectins. One susceptible and one tolerant population were used in the study; insects were exposed to the insecticide concentrations recommended by the manufacturers. The midgut was collected after an interval of 20 min and analyzed using optical microscopy.

RESULTS

Bt fomulation interferes with the glycogen content, whereas XenTari® interferes with the protein content, irrespective of the level of susceptibility. High expression of GalNAc residues was observed using soybean lectin labeling, indicating a direct relationship between the glycosylation pattern and susceptibility to Bt fomulation in the Pelotas population.

CONCLUSION

The use of Bt fomulation caused greater alterations in the larval intestinal histophysiology compared to the use of XenTari®. © 2018 Society of Chemical Industry
Optimal planning of phase II/III programs for clinical trials with multiple endpoints
Authors: Kieser Meinhard , Kirchner Marietta , Dölger Eva , Götte Heiko
Published: April 2018

Owing to increased costs and competition pressure, drug development becomes more and more challenging. Therefore, there is a strong need for improving efficiency of clinical research by developing and applying methods for quantitative decision making. In this context, the integrated planning for phase II/III programs plays an important role as numerous quantities can be varied that are crucial for cost, benefit, and program success. Recently, a utility‐based framework has been proposed for an optimal planning of phase II/III programs that puts the choice of decision boundaries and phase II sample sizes on a quantitative basis. However, this method is restricted to studies with a single time‐to‐event endpoint. We generalize this procedure to the setting of clinical trials with multiple endpoints and (asymptotically) normally distributed test statistics. Optimal phase II sample sizes and go/no‐go decision rules are provided for both the “all‐or‐none” and “at‐least‐one” win criteria. Application of the proposed method is illustrated by drug development programs in the fields of Alzheimer disease and oncology.
Costunolide promotes imatinib‐induced apoptosis in chronic myeloid leukemia cells via the Bcr/Abl–Stat5 pathway
Authors: Cai Hong , He Xiaolin , Yang Chunhui
Published: April 2018

Costunolide, a sesquiterpene lactone, is a small molecular monomer extracted from Inula helenium (Compositae). In the present study, we assessed the antileukemia effects of costunolide on the human chronic myeloid leukemia cell line K562 and its combined activity with imatinib. A Cell Counting Kit‐8 assay demonstrated that costunolide significantly inhibited K562 cell proliferation and enhanced imatinib‐induced anti‐proliferative activity. We found that costunolide significantly induced mitochondrial apoptosis in K562 cells by modulating the protein levels of Bcl‐2 family members and by inducing caspase activation. Costunolide promoted imatinib‐induced apoptosis via the Bcr/Abl–signal transducer and activator of transcription 5 pathway. Costunolide inhibited proliferation by inducing cell cycle arrest in the G2/M phase by decreasing cyclin B1 and cyclin‐dependent kinase 2 expression and increasing p21 expression. Together, these results demonstrate that costunolide may be a potent therapeutic agent against chronic myeloid leukemia.
GLM‐based statistical control r‐charts for dispersed count data with multicollinearity between input variables
Authors: Park Kayoung , Kim Jong‐Min , Jung Dongmin
Published: April 2018

The Poisson distribution is commonly used to describe count data for a control chart. However, it may not be appropriate for overdispersion or underdispersion. Thus, it is necessary to generalize the control chart to work well in such situations. This paper proposes a strategy for monitoring dispersed count data with multicollinearity between input variables by combining generalized linear model and principal component analysis. In the strategy, the generalized linear model using flexible distributions is performed on principal component scores from principal component analysis. The deviance residuals from the fitted model are then used to monitor the process. Simulation is conducted for performance under various situations. Also, a real dataset that is not suitable for a classical control chart is used in our example. The results from the simulated data and real data example support our proposed method.
Mechanistic dichotomy in the gas‐phase addition of NO3 to polycyclic aromatic hydrocarbons: Theoretical study
Authors: Ghigo Giovanni , Maranzana Andrea , Tonachini Glauco
Published: April 2018

The gas‐phase addition mechanism of the NO3 radical (an important tropospheric nocturnal oxidizing species) to some selected polycyclic aromatic hydrocarbons (PAHs), important pollutants of the troposphere, has been computationally analysed. Purpose of this work is to verify whether the reaction can take place through a mechanism different from the simple radical addition to the π aromatic system. This mechanism could consist in an Electron Transfer (ET) from the aromatics to NO3, thus generating an aromatic radical‐cation and a nitrate anion at long CO distances. The coulomb attraction should finally bind the two species and generate the radical adduct without any electronic energy barrier. The CASPT2 results show that, while benzene and naphthalene react with NO3 through a plain radical mechanism, anthracene reacts by a mechanism with a partial ET character, and pentacene reacts with a sort of inner‐sphere ET pathway. These results concur to explain the high reactivity of NO3 with larger PAHs whose ionization energy is below 7 eV and could be important in studies of environmental PAH oxidative degradation.
Filling in the gaps: A theoretical grounding for an education programme for adolescent socioemotional and vocational development in Ireland
Authors: Clerkin Aidan
Published: April 2018

Since the 1970s, schools in Ireland have offered an optional programme known as ‘Transition Year’ midway through secondary education, when students are typically 15 years old. It lasts one academic year and aims to promote maturity, social development and vocational exploration, and to give students a chance to develop personal and intellectual interests in the absence of high‐stakes examination pressure. On returning to more conventional classes, participants are expected to be better prepared to study and better prepared for life beyond school. The evolution of Transition Year over nearly half a century has been driven primarily by committed teachers and particular policy decisions, but, despite increasing uptake, it has lacked a strong theoretical grounding. This has contributed to a measure of public ambivalence and vulnerability to political vicissitudes. This paper reviews the extant literature on Transition Year, situates Transition Year in the context of selected aspects of the psychological literature on socioemotional development, highlights avenues for future research and discusses its relevance to social and emotional learning in global education beyond Ireland.
Useful information for stakeholder engagement: A multivariate proposal of an Industrial Corporate Social Responsibility Practices Index
Authors: Amor‐Esteban Víctor , Galindo‐Villardón Mª‐Purificación , García‐Sánchez Isabel‐María
Published: April 2018

The aim of this paper is to create an industrial corporate social responsibility practices index (ICSRPI) that allows us to determine the level of sustainable business commitment in the main industries. The ICSRPI allows simplification and quantification of corporate social responsibility (CSR) practices; identification of those industries which present greater deficiencies in sustainability systems to facilitate the planning of various improvement actions; and provision of pertinent information on environmental and social issues to guide stakeholders in their decision‐making processes. In this sense, empirically, the ICSRPI reveals that companies from more polluting sectors, such as oil and gas, chemical, paper or mining, are perceived as having high environmental risk and are the leaders in sustainable development. Companies from less polluting sectors, such as the media or financial services, have lower CSR scores; however, they present high values in social issues, giving higher priority to business ethics and the rights of employees.
High Efficiency Light‐Emitting Transistor with Vertical Metal–Oxide Heterostructure
Authors: Liu Xiang , Kuang Wenjian , Ni Haibin , Tao Zhi , Chang Jianhua , Liu Qinquan , Ge Junxiang , Li Chi , Dai Qing
Published: April 2018

The monolithic integration of light‐emission with a standard logic transistor is a much‐desired multifunctionality. Here, a high‐efficiency light‐emitting transistor (LET) employing an inorganic quantum dots (QDs) emitter and a laser‐annealed vertical metal–oxide heterostructure is reported. The experimental results show that the peak efficiency and luminance of this QDs LET (QLET) are 11% and 8000 cdm−2, respectively at a monochromatic emitting light wavelength of 585 nm. As far as it is known, these are among the highest values ever achieved for LETs. More importantly, the QLET exhibits an ultrahigh electron mobility of up to 25 cm2 V−1 S−1, a lower efficiency roll‐off (7% at high 3000 cdm−2), and excellent stability with long‐duration gate stress switching cycles. Additionally, this approach is compatible with those used in conventional large‐area silicon electronic manufacturing and can enable a scalable and cost‐effective procedure for future integrated versatile displays and lighting applications.
State‐of‐the‐Art Design and Rapid‐Mixing Production Techniques of Lipid Nanoparticles for Nucleic Acid Delivery
Authors: Evers Martijn J. W. , Kulkarni Jayesh A. , van der Meel Roy , Cullis Pieter R. , Vader Pieter , Schiffelers Raymond M.
Published: April 2018

Lipid nanoparticles (LNPs) are currently the most clinically advanced nonviral carriers for the delivery of small interfering RNA (siRNA). Free siRNA molecules suffer from unfavorable physicochemical characteristics and rapid clearance mechanisms, hampering the ability to reach the cytoplasm of target cells when administered intravenously. As a result, the therapeutic use of siRNA is crucially dependent on delivery strategies. LNPs can encapsulate siRNA to protect it from degradative endonucleases in the circulation, prevent kidney clearance, and provide a vehicle to deliver siRNA in the cell and induce its subsequent release into the cytoplasm. Here, the structure and composition of LNP–siRNA are described including how these affect their pharmacokinetic parameters and gene‐silencing activity. In addition, the evolution of LNP–siRNA production methods is discussed, as the development of rapid‐mixing platforms for the reproducible and scalable manufacturing has facilitated entry of LNP–siRNA into the clinic over the last decade. Finally, the potential of LNPs in delivering other nucleic acids, such as messenger RNA and CRISPR/Cas9 components, is highlighted alongside how a design‐of‐experiment approach may be used to improve the efficacy of LNP formulations.
Perovskite‐Based Nanocrystals: Synthesis and Applications beyond Solar Cells
Authors: Wang Ning , Liu Wenbo , Zhang Qichun
Published: April 2018

The recent progress in perovskite nanocrystals, including synthetic methods and their applications beyond solar cells, is discussed. Specifically, different synthetic routes to prepare various perovskite nanocrystals are considered, followed by their applications, including light‐emitting diodes, amplified spontaneous emission and lasing, photodetectors, resistance random access memory devices, and piezoelectric nanogenerators. Finally, an outlook for the future potential applications and possible challenges of perovskite nanocrystals is addressed.
3D Macroporous MoxC@N‐C with Incorporated Mo Vacancies as Anodes for High‐Performance Lithium‐Ion Batteries
Authors: Liu Shenghong , Li Feng , Wang Dan , Huang Chunmao , Zhao Yanming , Baek Jong‐Beom , Xu Jiantie
Published: April 2018

High electronic conductivity, low average working voltage, and high theoretical capacities enable molybdenum carbide‐based materials as promising anodes for lithium‐ion batteries (LIBs). Apart from the increase in the number of additional active sites, further enhancement in the specific activity of the active sites is also an effective way to improve the electrochemical performance of the molybdenum carbide‐based electrodes. Here, a series of 3D cross‐linked macroporous MoxC@N‐C nanocrystals with rich incorporated Mo vacancies, high specific activity of active sites, and nitrogen‐doped carbon (N‐C) coating are designed and synthesized using a simple method. Benefitting from its 3D robust structures for the rapid transporting and additional storage of Li+, the MoxC@N‐C‐2.5 displays a high initial reversible capacity of 879.3 mAh g−1 at 0.05 A g−1. Moreover, the MoxC@N‐C‐2.5 shows a high discharge capacity of 825.3 mAh g−1 at 0.5 A g−1 with an initial capacity retention of 61.9% after 200 cycles. As expected, this facile strategy can be extended to the fabrication of other nanocomposites with rich defects, numerous porous structures, and heteroatoms doped carbon coating as electrodes toward high‐performance LIBs.
The Internet of Things and the Smart City: Legal challenges with digital forensics, privacy, and security
Authors: Losavio Michael M. , Chow K. P. , Koltay Andras , James Joshua
Published: April 2018

The explosive growth of information and communications technologies (ICTs) as manifested in Smart Cities and the Internet of Things (IoT) creates more and more computable data with myriad benefits. They also produce ever more digital evidence of people's lives in all contexts, with commensurately greater potential risks to the safety and rights of citizens. Digital/computational forensics and analytics, used to combat crime, are the vanguard of the collision of these with public policy as to privacy and personal autonomy. They bring the evidentiary fruits of this technology directly to the policymaker, police investigator, and the judge. And to the marketer, stalker, and extortionist. We examine this technical‐legal interaction and how it might inform as to privacy and security with the IoT and the Smart City.
Agent‐based simulation framework and consensus algorithm for observing systems with adaptive modularity
Authors: Gallud Ximo , Selva Daniel
Published: April 2018

In this era of the “big data revolution,” the desired capabilities of Earth Observing Systems are growing fast: we need ever more frequent data sets, covering a larger part of the frequency spectrum, with lower latency, and higher spatial resolution. To better address these needs, the space systems community has been exploring the value of shifting from highly monolithic architectures, in which large and isolated spacecraft carry multiple instruments with synergistic and complementary goals, toward more distributed architectures, where the functions of these large systems are partitioned into a larger number of smaller satellites. In this paper, we present an agent‐based simulation framework that can help systems engineers assess whether or not it makes sense to be able to “change system modularity during operations” by means of temporary coalitions. Systems of observing autonomous vehicles work together to perform a set of observational tasks. The vehicles can decide to form physical coalitions with other vehicles for collective sensing of a target, when no agent alone can carry out the task, or individual observation results in degraded satisfaction. The framework extends the well‐known decentralized Coupled‐Constraint Consensus‐Based Bundle Algorithm to multivehicle single‐task allocation and introduces constraints on the formation of coalitions, so that agents can create or split a coalition depending on the benefits and costs associated with these actions. The framework is described in detail and demonstrated on a case study.
The Hydrolysis of AlN Powder – A Powerful Tool in Advanced Materials Engineering
Authors: Kocjan Andraž
Published: April 2018

The tendency for aluminium nitride (AlN) powder to undergo hydrolysis, which can lead to a complete degradation of the material, is unique in metal nitrides. Although this form of hydrolysis has been known for a long time, it is generally considered as a nuisance, because it prevents the aqueous powder processing of AlN‐based ceramics. However, careful investigations of the course of hydrolysis, the reaction kinetics and the evolution of aluminium hydroxides have uncovered exceptional possibilities for the exploitation of this naturally driven process in the area of advanced materials engineering. It can be employed as superior synthesis path for hierarchically‐assembled, mesoporous alumina powders or coatings consisting of 2D nanocrystalline lamellas. The beneficial surface characteristics of the powder serve as an ideal template for further modifications useful in catalysis, while the powder's flowability enables facile preparation of high‐performance hierarchically porous structures. The coatings, on the other hand, are suitable as templates for superhydrophobic surfaces or as adhesive coatings for cementing zirconia dental ceramics. Finally, the hydrolysis‐assisted solidification (HAS) process has proved to be an important asset in the processing science and technology for fabrication of porous and dense ceramics and nanocomposites.
Implementation of failure modes and effects analysis in detergent production companies: A case study
Authors: Ershadi M. J. , Ershadi M. M.
Published: April 2018

Failure mode and effect analysis (FMEA) is the most important method used by production companies to identify potential risks regarding occupational and health hazards and environmental hazards. This method is also useful in defining preventive actions to reduce the effects of these risks. Detergent production companies continually encounter many occupational and health hazards and environmental hazards, the management and reduction of which requires complex assessment in real‐world applications. This paper presents a framework for application of FMEA for managing and ranking identified risks in detergent production companies. A case study is presented to show the application of an FMEA to investigate the results of its application and the outcomes from the analysis. A risk priority number (RPN) is proposed for each distinct risk. The application of FMEA in the detergent production company resulted in grouping the RPN of the identified risks into four different categories. The main corrective actions, which are determined to reduce the RPNs, are presented in this paper. Improving the RPN of the main risks is observed after executing the corrective actions.
Morphometry of the nulliparous pelvic floor
Authors: Nesbitt‐Hawes E. M. , Dietz H. P. , Abbott J. A.
Published: April 2018

Objectives

To describe morphometry of the pelvic floor in a large population of nulliparous women, comparing those with and those without pelvic pain. We also aimed to assess its association with characteristics such as age and body mass index (BMI).

Methods

This was a prospective study performed between January 2013 and November 2015 in non‐pregnant nulliparous women attending a general gynecology clinic. Following collection of demographic data, women were examined using translabial four‐dimensional (4D) ultrasound. Dynamic volumes of pelvic floor muscle were obtained at rest, on maximal contraction and on Valsalva maneuver, and analyzed at a later date by an assessor blinded to demographic details. Standard measurements for each volume included levator hiatal area and anteroposterior and transverse diameters, and pubovisceral muscle length and width. Subanalysis was performed comparing women with and those without pelvic pain. Linear regression analysis was performed to assess the association between characteristics, including age and BMI, and levator hiatal area at rest.

Results

Three hundred and sixty eight nulliparous women were examined using translabial 4D ultrasound. Median levator hiatal area was 10.62 cm2 at rest, 11.95 cm2 on Valsalva maneuver and 8.18 cm2 on maximal contraction. There was no difference between women with and those without pelvic pain when comparing biometric measurements of the pelvic floor musculature, except for in pubovisceral muscle width during the contraction phase. Regression analysis demonstrated that higher age and BMI were associated with increased levator hiatal area measurement.

Conclusions

Pelvic floor morphometry in nulliparous women is unchanged by pelvic pain, but levator hiatal area is increased in women with higher BMI and age. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
An Unusual Layered Crystal Packing Gives Rise to a Superior Thermal Stability of Energetic Salt of 3,6‐Bishydrazino‐1,2,4,5‐tetrazine
Authors: Zhang Gu‐Dan , Wang Zhen , Zhang Jian‐Guo
Published: April 2018

Five energetic salts of 3,6‐bishydrazino‐1,2,4,5‐tetrazine (BHT), namely (BHT)2(NTO)3 (3), (BHT)(BTT)·2H2O (4), (BHT)(DNP)2 (5), (BHT)(NATr)2 (6), and (BHT)(FOX‐7)2 (7), were synthesized and fully characterized by elemental analysis, FT‐IR, and mass spectra. The crystal structures of salts 3 and 4 were obtained and determined. Sensitivities towards outside stimuli and thermal behaviors of all the compounds were investigated, besides, thermodynamics of both 3 and 4 were calculated as well. The compounds 3–7 exhibit splendid thermal stabilities and satisfactory sensitivities simultaneously. Notably, unlike the previously known layered packing, compound 4 was found to adopt an unusual layered crystal packing with arch layers alternately arranged upward or downward. It may play an important role in contributing to its superior thermal stability (350 °C), providing an enlightening thinking to design new highly thermal stable energetic materials.
Membrane paradigm and RG flows for anomalous holographic theories
Authors: Copetti Christian , Fernández-Pendás Jorge
Published: April 2018

Abstract

Holographic RG flows can be better understood with the help of radially conserved charges. It was shown by various authors that the bulk gauge and diffeomorphism symmetries lead to the conservation of the zero mode of the holographic U(1) current and, if the spacetime is stationary, to that of the holographic heat current. In describing dual theories with ’t Hooft anomalies the bulk gauge invariance is broken by Chern-Simons terms. We show that conservation laws can still be derived and used to characterize the anomalous transport in terms of membrane currents at the horizon. We devote particular attention to systems with gravitational anomalies. These are known to be problematic due to their higher derivative content. We show that this feature alters the construction of the membrane currents in a way which is deeply tied with the anomalous gravitational transport.