bluuebunny/crossref_metadata_2025 huggingface dataset:
Abandoning statistical significance is both sensible and practical
Authors: Amrhein Valentin , Gelman Andrew , Greenland Sander , McShane Blakeley B
Published: April 2019

To the Editor of JAMA

Dr Ioannidis writes against our proposals to abandon statistical significance in scientific reasoning and publication, as endorsed in the editorial of a recent special issue of an American Statistical Association journal devoted to moving to a “post p<0.05 world.” We appreciate that he echoes our calls for “embracing uncertainty, avoiding hyped claims…and recognizing ‘statistical significance’ is often poorly understood.” We also welcome his agreement that the “interpretation of any result is far more complicated than just significance testing” and that “clinical, monetary, and other considerations may often have more importance than statistical findings.”

Nonetheless, we disagree that a statistical significance-based “filtering process is useful to avoid drowning in noise” in science and instead view such filtering as harmful. First, the implicit rule to not publish nonsignificant results biases the literature with overestimated effect sizes and encourages “hacking” to get significance. Second, nonsignificant results are often wrongly treated as zero. Third, significant results are often wrongly treated as truth rather than as the noisy estimates they are, thereby creating unrealistic expectations of replicability. Fourth, filtering on statistical significance provides no guarantee against noise. Instead, it amplifies noise because the quantity on which the filtering is based (the p-value) is itself extremely noisy and is made more so by dichotomizing it.

We also disagree that abandoning statistical significance will reduce science to “a state of statistical anarchy.” Indeed, the journal Epidemiology banned statistical significance in 1990 and is today recognized as a leader in the field.

Valid synthesis requires accounting for all relevant evidence—not just the subset that attained statistical significance. Thus, researchers should report more, not less, providing estimates and uncertainty statements for all quantities, justifying any exceptions, and considering ways the results are wrong. Publication criteria should be based on evaluating study design, data quality, and scientific content—not statistical significance.

Decisions are seldom necessary in scientific reporting. However, when they are required (as in clinical practice), they should be made based on the costs, benefits, and likelihoods of all possible outcomes, not via arbitrary cutoffs applied to statistical summaries such as p-values which capture little of this picture.

The replication crisis in science is not the product of the publication of unreliable findings. The publication of unreliable findings is unavoidable: as the saying goes, if we knew what we were doing, it would not be called research. Rather, the replication crisis has arisen because unreliable findings are presented as reliable.
NLRP12 suppresses hepatocellular carcinoma via downregulation of cJun N-terminal kinase activation in the hepatocyte
Authors: Udden SM Nashir , Kwak Youn-Tae , Godfrey Victoria , Khan Md Abdul Wadud , Khan Shahanshah , Loof Nicolas , Peng Lan , Zhu Hao , Zaki Hasan
Published: April 2019

Hepatocellular carcinoma (HCC) is a deadly human cancer associated with chronic inflammation. The cytosolic pathogen sensor NLRP12 has emerged as a negative regulator of inflammation, but its role in HCC is unknown. Here we investigated the role of NLRP12 in HCC using mouse models of HCC induced by carcinogen diethylnitrosamine (DEN). Nlrp12-/- mice were highly susceptible to DEN-induced HCC with increased inflammation, hepatocyte proliferation, and tumor burden. Consistently, Nlrp12-/- tumors showed higher expression of proto-oncogenes cJun and cMyc and downregulation of tumor suppressor p21. Interestingly, antibiotics treatment dramatically diminished tumorigenesis in Nlrp12-/- mouse livers. Signaling analyses demonstrated higher JNK activation in Nlrp12-/- HCC and cultured hepatocytes during stimulation with microbial pattern molecules. JNK inhibition or NLRP12 overexpression reduced proliferative and inflammatory responses of Nlrp12-/- hepatocytes. In summary, NLRP12 negatively regulates HCC pathogenesis via downregulation of JNK-dependent inflammation and proliferation of hepatocytes.
CCL5 promotes breast cancer recurrence through macrophage recruitment in residual tumors
Authors: Walens Andrea , DiMarco Ashley V , Lupo Ryan , Kroger Benjamin R , Damrauer Jeffrey S , Alvarez James V
Published: April 2019

Over half of breast-cancer-related deaths are due to recurrence 5 or more years after initial diagnosis and treatment. This latency suggests that a population of residual tumor cells can survive treatment and persist in a dormant state for many years. The role of the microenvironment in regulating the survival and proliferation of residual cells following therapy remains unexplored. Using a conditional mouse model for Her2-driven breast cancer, we identify interactions between residual tumor cells and their microenvironment as critical for promoting tumor recurrence. Her2 downregulation leads to an inflammatory program driven by TNFα/NFκB signaling, which promotes immune cell infiltration in regressing and residual tumors. The cytokine CCL5 is elevated following Her2 downregulation and remains high in residual tumors. CCL5 promotes tumor recurrence by recruiting CCR5-expressing macrophages, which may contribute to collagen deposition in residual tumors. Blocking this TNFα-CCL5-macrophage axis may be efficacious in preventing breast cancer recurrence.
Cerebellar folding is initiated by mechanical constraints on a fluid-like layer without a cellular pre-pattern
Authors: Lawton Andrew K , Engstrom Tyler , Rohrbach Daniel , Omura Masaaki , Turnbull Daniel H , Mamou Jonathan , Zhang Teng , Schwarz J M , Joyner Alexandra L
Published: April 2019

Models based in differential expansion of elastic material, axonal constraints, directed growth, or multi-phasic combinations have been proposed to explain brain folding. However, the cellular and physical processes present during folding have not been defined. We used the murine cerebellum to challenge folding models with in vivo data. We show that at folding initiation differential expansion is created by the outer layer of proliferating progenitors expanding faster than the core. However, the stiffness differential, compressive forces, and emergent thickness variations required by elastic material models are not present. We find that folding occurs without an obvious cellular pre-pattern, that the outer layer expansion is uniform and fluid-like, and that the cerebellum is under radial and circumferential constraints. Lastly, we find that a multi-phase model incorporating differential expansion of a fluid outer layer and radial and circumferential constraints approximates the in vivo shape evolution observed during initiation of cerebellar folding.
Cloning and characterization of a tyrosine decarboxylase involved in the biosynthesis of galanthamine inLycoris aurea
Authors: Wang Rong , Han Xiaokang , Xu Sheng , Xia Bing , Jiang Yumei , Xue Yong , Wang Ren
Published: April 2019

Background

Galanthamine, one kind of Amaryllidaceae alkaloid extracted from theLycorisspecies, is used in the treatment of Alzheimer’s disease. In regards to medical and economic importance, the biosynthesis and regulatory mechanism of the secondary metabolites inLycorisremain uninvestigated.

Methods

BLAST was used to identify the sequence of tyrosine decarboxylase in the transcriptome ofLycoris aurea(L’Hér) Herb. The enzyme activity of this TYDC was determined by using heterologous expressed protein in theEscherichia colicells. The related productive contents of tyramine were detected using High Performance Liquid Chromatography (HPLC). According to the available micro RNA sequencing profiles and degradome database ofL. aurea, microRNA396 were isolated, which targets toLaTYDC1and RNA Ligase-Mediated-Rapid Amplification of cDNA Ends (RLM-RACE) were used to confirm the cleavage. The expression levels of miR396 andLaTYDC1were measured using a quantitative real-time polymerase chain reaction (qRT-PCR).

Results

LaTYDC1 was mainly expressed in root, bulb, leaf and flower fitting the models for galanthamine accumulation. This decarboxylase efficiently catalyzes tyrosine to tyramine conversion. Under methyl jasmonate (MeJA) treatment, the expression ofLaTYDC1and the content of tyramine sharply increase. The use of RLM-RACE confirms that miR396 promotes the degradation ofLaTYDC1mRNA. Under MeJA treatment, the expression of miR396 was suppressed while the expression level ofLaTYDC1sharply increased. Following the increase of the miR396 transcriptional level,LaTYDC1was significantly repressed.

Conclusion

LaTYDC1 participates in the biosynthesis of galanthamine, and is regulated by miR396. This finding also provides genetic strategy for improving the yield of galanthamine in the future.
Characterization of the iPSC-derived conditioned medium that promotes the growth of bovine corneal endothelial cells
Authors: Liu Qing , Guo Yonglong , Liu Shiwei , Wang Peiyuan , Xue Yunxia , Cui Zekai , Chen Jiansu
Published: April 2019

Corneal endothelial cells (CECs) maintain corneal transparency and visual acuity. However, the limited proliferative capability of these cells in vitro has prompted researchers to find efficient culturing techniques for them. The aim of our study was to evaluate the use of conditioned medium (CM) obtained from induced pluripotent stem cells (iPSCs) as a source for the effective proliferation of bovine CECs (B-CECs). In our study, the proliferative ability of B-CECs was moderately enhanced when the cells were grown in 25% iPSC conditioned medium (iPSC-CM). Additionally, hexagonal cell morphology was maintained until passage 4, as opposed to the irregular and enlarged shape observed in control corneal endothelial medium (CEM). B-CECs in both the 25% iPSC-CM and CEM groups expressed and Na+-K+-ATPase. The gene expression levels of NIFK, Na+-K+-ATPase, Col4A and Col8A and the percentage of cells entering S and G2 phases were higher in the iPSC-CM group. The number of apoptotic cells also decreased in the iPSC-CM group. In comparison to the control cultures, iPSC-CM facilitated cell migration, and these cells showed better barrier functions after several passages. The mechanism of cell proliferation mediated by iPSC-CM was also investigated, and phosphorylation of Akt was observed in B-CECs after exposure to iPSC-CM and showed sustained phosphorylation induced for up to 180 min in iPSC-CM. Our findings indicate that iPSC-CM may employ PI3-kinase signaling in regulating cell cycle progression, which can lead to enhanced cellular proliferation. Effective component analysis of the CM showed that in the iPSC-CM group, the expression of activin-A was significantly increased. If activin-A is added as a supplement, it could help to maintain the morphology of the cells, similar to that of CM. Hence, we conclude that activin-A is one of the effective components of CM in promoting cell proliferation and maintaining cell morphology.
Identification and expression analysis of the GDSL esterase/lipase family genes, and the characterization of SaGLIP8 in Sedum alfredii Hance under cadmium stress
Authors: Li He , Han Xiaojiao , Qiu Wenmin , Xu Dong , Wang Ying , Yu Miao , Hu Xianqi , Zhuo Renying
Published: April 2019

Background

The herb Sedum alfredii (S. alfredii) Hance is a hyperaccumulator of heavy metals (cadmium (Cd), zinc (Zn) and lead (Pb)); therefore, it could be a candidate plant for efficient phytoremediation. The GDSL esterase/lipase protein (GELP) family plays important roles in plant defense and growth. Although the GELP family members in a variety of plants have been cloned and analyzed, there are limited studies on the family’s responses to heavy metal-stress conditions.

Methods

Multiple sequence alignments and phylogenetic analyses were performed according to the criteria described. A WGCNA was used to construct co-expression regulatory networks. The roots of S. alfredii seedlings were treated with 100 µM CdCl2 for qRT-PCR to analyze expression levels in different tissues. SaGLIP8 was transformed into the Cd sensitive mutant strain yeast Δycf1 to investigate its role in resistance and accumulation to Cd.

Results

We analyzed GELP family members from genomic data of S. alfredii. A phylogenetic tree divided the 80 identified family members into three clades. The promoters of the 80 genes contained certain elements related to abiotic stress, such as TC-rich repeats (defense and stress responsiveness), heat shock elements (heat stress) and MYB-binding sites (drought-inducibility). In addition, 66 members had tissue-specific expression patterns and significant responses to Cd stress. In total, 13 hub genes were obtained, based on an existing S. alfredii transcriptome database, that control 459 edge genes, which were classified into five classes of functions in a co-expression subnetwork: cell wall and defense function, lipid and esterase, stress and tolerance, transport and transcription factor activity. Among the hub genes, Sa13F.102 (SaGLIP8), with a high expression level in all tissues, could increase Cd tolerance and accumulation in yeast when overexpressed.

Conclusion

Based on genomic data of S. alfredii, we conducted phylogenetic analyses, as well as conserved domain, motif and expression profiling of the GELP family under Cd-stress conditions. SaGLIP8 could increase Cd tolerance and accumulation in yeast. These results indicated the roles of GELPs in plant responses to heavy metal exposure and provides a theoretical basis for further studies of the SaGELP family’s functions.
Materialidad, formas de vida y animalidad en películas de Ignacio Agüero y José Luis Torres Leiva
Authors:   Pontificia Universidad Católica de Chile, De los Ríos Valeria
Published: April 2019

Este artículo explora los intercambios entre humanos y no humanos a partir de dos películas chilenas contemporáneas: El otro día (2012), de Ignacio Agüero, y El viento sabe que vuelvo a casa (2016), de José Luis Torres Leiva. Estas películas configuran un ensamblaje en el que se genera una conexión a partir de la figura de Agüero, quien dirige una y protagoniza la otra. Ambos filmes organizan sus narrativas a partir de un dispositivo espacial y topográfico que facilita el contacto entre materialidades humanas y no humanas. Estas películas se construyen a partir del diálogo y de la relación con otros, pero también suponen la mirada atenta del entorno, en el que emergen presencias orgánicas e inorgánicas que afectan el tratamiento de la temporalidad, el montaje y las distinciones genéricas entre documental y ficción.
Operación Termita: por una segunda línea en el cine chileno
Authors:   Centro de Estudios Latinoamericanos Universidad de Chile, Pinto Iván , González Sebastián ,   The University of Edinburgh United Kingdom, Munjin Vanja ,   Universidade Nova de Lisboa Portugal
Published: April 2019

Desde la explosión de un nuevo cine chileno a mediados de la década del 2000, la discusión sobre sus fuentes, motivaciones, narrativas y estéticas ha enfocado sus esfuerzos en la constitución de un canon del cine chileno contemporáneo bajo el apelativo de “Novísimo cine chileno”. Al interior de de esa discusión este artículo busca dividir líneas de trabajo, estableciendo una división entre una primera línea festivalera y de reconocimiento internacional y una segunda que la tensiona, trayendo a discusión obras menos visibilizadas que desde una operación “termita” carcome las intenciones proselitistas de cualquier índole
The Impacts of Distributive Justice and Perceived Organizational Support on Turnover Intention within The Poultry Industry
Authors: Tanoto Sherly Rosalina , Sugiharto Merry Yuanita
Published: April 2019

Increased numbers of job-hopping in Indonesia might result in negative costs for organizations. Earlier research in turnover intention tends to emphasize organizational commitment yet it neglects the importance of perceived fairness in allocating results and perceived support from organizations. The aim of this study is to investigate the influence of distributive justice and perceived organizational support to turnover intention in a company within the poultry industry. This study implements quantitative method by administering surveys to 142 fulltime employees. Partial Least Square was utilized to test the research model. Results of this study demonstrated that perceived organizational support is the most significant factor for turnover intention and distributive justice has higher influence on perceived organizational support compared with turnover intention. These findings contribute to the development of employers and managers’ initiatives to promote support and distributive fairness toward their employees.
Capping Silica Nanoparticles with Tryptophan‐Mediated Cucurbit[8]uril Complex for Targeted Intracellular Drug Delivery Triggered by Tumor‐Overexpressed IDO1 Enzyme
Authors: Qiao Haishi , Jia Jing , Shen Haowen , Zhao Sibo , Chen Enping , Chen Wei , Di Bin , Hu Chi
Published: April 2019

Nanosystems responsive to tumor‐specific enzymes are considered as a highly attractive approach to intracellular drug release for targeted cancer therapy. Mesoporous silica nanoparticles are capped with tryptophan‐mediated cucurbit[8]uril complex with Fe3O4 to minimize the premature drug leakage while being able to deliver the payload on demand at the target tissue. The supramolecular interaction between tryptophan and cucurbit[8]uril is disrupted in the presence of indoleamine 2,3‐dioxygenase 1 (IDO1) enzyme (abundant in the tumor intracellular microenvironment), which catalyzes the metabolism of tryptophan into N‐formylkynurenine, resulting in the disassembly of the “gate‐keeper” of the nanocarriers and intracellular release of therapeutics exclusively in tumor cells. The drug release from the nanocarrier with high selectivity to overexpressed IDO1 enzyme induces significant cytotoxicity against HepG2 cells in vitro, as well as the superior antitumor effects in vivo. This robust supramolecular nanosystem with sophisticated structure and property provides a promising platform for intracellular drug release targeting the intrinsic microenvironmental enzyme inside the tumor cells.
Effect of Electric Field on the Lubricating Performance of Ga‐Based Liquid Metal
Authors: Guo Jie , Cheng Jun , Tan Hui , Zhu Shengyu , Qiao Zhuhui , Yang Jun , Liu Weimin
Published: April 2019

Ga‐based liquid metal (GLM) can be used as a current‐carrying lubricant, due to its combination of excellent electrical conductivity and good lubricity. However, the influence of electric field parameters on the lubrication mechanism of GLM is still unclear. This paper attempts to investigate the influence of current magnitude, voltage magnitude, current direction, and load on the lubrication behaviors of GLM at atmosphere and room temperature (≈26 °C). It is found that the interface action mechanism induced by an electric field is mainly reflected in four aspects, namely, Joule heating effect, electric field force, electrochemical effect, and electromigration effect. These interfacial physical and chemical effects are governed by the current magnitude, voltage magnitude, current direction, and load, bringing about distinct frictional products and thereby influencing the lubrication behaviors. Briefly, FeGa3 can only be formed when the current reaches 6 A and the load is above 40 N, and it has obvious friction‐reducing properties, but increases the wear due to its low content. When the frictional product is just the Ga‐rich film, the increase of oxidation degree is detrimental to the wear resistance.
Generating Energy from Air: Solid State Planar Concentration Cell Based on Graphene Oxide
Authors: Wei Di
Published: April 2019

Adv. Mater. Technol. 2016, 1, 1600145

The above article from Advanced Materials Technologies, published online on 5 September 2016 and in Volume 1, Issue 8 in Wiley Online Library (http://onlinelibrary.wiley.com), has been retracted at the request of Nokia, and in agreement with the journal Editor‐in‐Chief and Wiley.

Following an investigation conducted by Nokia, the retraction has been agreed because it was ascertained by Nokia that the author reported results which included other people's ideas and experiments without their knowledge and consent, that he did not acknowledge all those involved in the study, and that he submitted the manuscript to the journal without prior vetting and authorization by Nokia, in violation of Nokia's policies.

[1] D. Wei, Adv. Mater. Technol. 2016, 1, 1600145, https://doi.org/10.1002/admt.201600145.
Synthesis of Benzo[a]quinolizidines via an Aza‐Michael/Oxidative Mannich Process
Authors: Jung Areum , Min Sun‐Joon
Published: April 2019

The synthesis of substituted benzo[a]quinolizidines via aza‐Michael addition of tetrahydroisoquinolines to alkyl vinyl ketones, followed by oxidative Mannich cyclization, is described. Various Michael adducts are easily prepared, and subsequent DDQ‐mediated oxidations stereoselectively afford the corresponding azacycles efficiently. Furthermore, the one‐pot aza‐Michael/oxidative Mannich process gave benzo[a]quinolizidines, thus providing a metal‐free and practical synthetic route to N‐heterocyclic building blocks.
Lipase‐Powered Mesoporous Silica Nanomotors for Triglyceride Degradation
Authors: Wang Lei , Hortelão Ana C. , Huang Xin , Sánchez Samuel
Published: April 2019

We report lipase‐based nanomotors that are capable of enhanced Brownian motion over long periods of time in triglyceride solution and of degrading triglyceride droplets that mimic “blood lipids”. We achieved about 40 min of enhanced diffusion of lipase‐modified mesoporous silica nanoparticles (MSNPs) through a biocatalytic reaction between lipase and its corresponding water‐soluble oil substrate (triacetin) as fuel, which resulted in an enhanced diffusion coefficient (ca. 50 % increase) at low triacetin concentration (<10 mm). Lipase not only serves as the power engine but also as a highly efficient cleaner for the triglyceride droplets (e.g., tributyrin) in PBS solution, which could yield potential biomedical applications, for example, for dealing with diseases related to the accumulation of triglycerides, or for environmental remediation, for example, for the degradation of oil spills.
Geochemical Sources and Availability of Amidophosphates on the Early Earth
Authors: Gibard Clémentine , Gorrell Ian B. , Jiménez Eddy I. , Kee Terence P. , Pasek Matthew A. , Krishnamurthy Ramanarayanan
Published: April 2019

Phosphorylation of (pre)biotically relevant molecules in aqueous medium has recently been demonstrated using water‐soluble diamidophosphate (DAP). Questions arise relating to the prebiotic availability of DAP and other amidophosphosphorus species on the early earth. Herein, we demonstrate that DAP and other amino‐derivatives of phosphates/phosphite are generated when Fe3P (proxy for mineral schreibersite), condensed phosphates, and reduced oxidation state phosphorus compounds, which could have been available on early earth, are exposed to aqueous ammonia solutions. DAP is shown to remain in aqueous solution under conditions where phosphate is precipitated out by divalent metals. These results show that nitrogenated analogues of phosphate and reduced phosphite species can be produced and remain in solution, overcoming the thermodynamic barrier for phosphorylation in water, increasing the possibility that abiotic phosphorylation reactions occurred in aqueous environments on early earth.
Facile Preparation of Spirolactones by an Alkoxycarbonyl Radical Cyclization–Cross‐Coupling Cascade
Authors: Weires Nicholas A. , Slutskyy Yuriy , Overman Larry E.
Published: April 2019

An alkoxycarbonyl radical cyclization–cross‐coupling cascade has been developed that allows functionalized γ‐butyrolactones to be prepared in one step from simple tertiary alcohol‐derived homoallylic oxalate precursors. The reaction succeeds with aryl and vinyl electrophiles and is compatible with heterocyclic fragments in both coupling partners. This chemistry allows for the rapid construction of spirolactones, which are of interest in drug discovery endeavors.
Synthesis, Properties, and Application of Tetrakis(pentafluoroethyl)gallate, [Ga(C2F5)4]−
Authors: Niemann Mark , Neumann Beate , Stammler Hans‐Georg , Hoge Berthold
Published: April 2019

Weakly coordinating anions (WCAs) are important for academic reasons as well as for technical applications. Tetrakis(pentafluoroethyl)gallate, [Ga(C2F5)4]−, a new WCA, is accessible by treatment of [GaCl3(dmap)] (dmap=4‐dimethylaminopyridine) with LiC2F5. The anion [Ga(C2F5)4]− proved to be reluctant towards deterioration by aqueous hydrochloric acid or lithium hydroxide. Various salts of [Ga(C2F5)4]− were synthesized with cations such as [PPh4]+, [CPh3]+, [(O2H5)2(OH2)2]2+, and [Li(dec)2]+ (dec=diethyl carbonate). Thermolysis of [(O2H5)2(OH2)2][Ga(C2F5)4]2 gives rise to a dihydrate of tris(pentafluoroethyl)gallane, [Ga(C2F5)3(OH2)2]. All products were characterized by NMR and IR spectroscopy, mass spectrometry, X‐ray diffraction, and elemental analysis. Furthermore, an outlook for the application of [Li(dec)2][Ga(C2F5)4] as a conducting salt in lithium‐ion batteries is presented.
Anatomical Assessment of the Adult Skeleton of Zebrafish Reared Under Different Thyroid Hormone Profiles
Authors: Keer Stephanie , Cohen Karly , May Catherine , Hu Yinan , McMenamin Sarah , Hernandez Luz Patricia
Published: April 2019

Thyroid hormone (TH) directs the growth and maintenance of tissues throughout the body during development and into adulthood, and plays a particularly important role in proper ossification and homeostasis of the skeleton. To better understand the roles of TH in the skeletogenesis of a vertebrate model, and to define areas of the skeleton that are particularly sensitive to developmental TH, we examined the effects of hypo‐ and hyperthyroidism on skeletal development in zebrafish. Performing a bone‐by‐bone anatomical assessment on the entire skeleton of adult fish, we found that TH is required for proper ossification, growth, morphogenesis, and fusion of numerous bones. We showed that the pectoral girdle, dermatocranium, Weberian apparatus, and dentary are particularly sensitive to TH, and that TH affects development of skeletal element regardless of bone type and developmental origin. Indeed, the hormone does not universally promote ossification: we found that developmental TH prevents ectopic ossification in multiple thin bones and within connective tissue of the jaw. In all, we found that TH regulates proper morphogenesis and ossification in the majority of zebrafish bones, and that the requirement for the hormone extends across bone types and developmental profiles. Anat Rec, 302:1754–1769, 2019. © 2019 American Association for Anatomy
Design, synthesis, in silico ADMET profile and GABA‐A docking of novel phthalazines as potent anticonvulsants
Authors: El‐Helby Abdel‐Ghany A. , Ayyad Rezk R. A. , Zayed Mohamed F. , Abulkhair Hamada S. , Elkady Hazem , El‐Adl Khaled
Published: April 2019

A new series of 2‐substituted‐2,3‐dihydrophthalazine‐1,4‐diones (2‒9) were designed and synthesized to evaluate their anticonvulsant activity. The neurotoxicity was assessed using the rotarod test. Molecular docking was performed for the synthesized compounds to assess their binding affinities as γ‐aminobutyric acid A (GABA‐A) receptor agonists as a possible mechanism of their anticonvulsant action, to rationalize their anticonvulsant activity in a qualitative way. The data obtained from the molecular modeling was strongly matched with that obtained from the biological screening, which revealed that compounds5a,9b, and9hshowed the highest binding affinities toward the GABA‐A receptor and also showed the highest anticonvulsant activities with relative potencies of 1.66, 1.63, and 1.61, respectively, compared with diazepam. The most active compounds5a,9b, and9hwere further tested against maximal electroshock seizures. Compounds5aand9bshowed 100% protection at a dose level of 125 µg/kg, while compound9hexhibited 83.33% protection at the same dose level. A GABA enzymatic assay was performed for these highly active compounds to confirm the obtained results and to explain the possible mechanism for their anticonvulsant action. These agents exerted low neurotoxicity and a high safety margin compared with valproate as a reference drug. Most of our designed compounds exhibited a good ADMET profile.
Porphyrin‐containing Polyimide with Enhanced Light Absorption and Photocatalysis Activity
Authors: Cui Zhiwei , Zhou Jun , Liu Teng , Wang Yicong , Hu Yue , Wang Ying , Zou Zhigang
Published: April 2019

A series of porphyrin‐containing polyimide (PI) photocatalysts were synthesized by a one‐step solvothermal method. Characterization results revealed that porphyrin was uniformly coupled into the PI framework through covalent bonding and the visible‐light absorption was greatly improved. The photodegradation activity of porphyrin‐containing PIs for methyl orange (MO) under visible light was enhanced significantly, with the highest pseudo‐first‐order rate constant 35 times higher than that of neat porphyrin and 10 times higher than that of porphyrin‐free PI. The enhancement is mainly attributed to an increased light harvesting accompanied by a varied HOMO level, which was clarified by control experiments, characterizations and theoretical calculations. This work provides an insight into multiple effects of dye molecules in dye‐containing heterogeneous photocatalysts.
Coexisting Cooperative Cognitive Micro‐/Nanorobots
Authors: Chang Xiaocong , Tang Wentian , Feng Yiwen , Yu Hao , Wu Zhiguang , Xu Tailin , Dong Huijuan , Li Tianlong
Published: April 2019

Interaction behaviors are a crucial, distinctive feature of organisms in ecological systems. Inspired by nature, micro‐/nanorobots also show interaction behaviors with a significant number of novel and advanced functionalities. The micro‐/nanoscale size and self‐driven abilities of micro‐/nanorobots have attracted considerable attention for potential applications. The mission of micro‐/nanorobots has evolved from basic mechanical transfer or assistance to a diverse range of complex tasks, such as targeted drug delivery, biosensing, and environmental remediation. Herein, we focus on the interaction behavior of coexisting cooperative cognitive (Tri‐Co) micro‐/nanorobots, summarize recent research, and classify the interactions into three broad types: with the environment, with robot peers, and with human external control.
A case–control analysis of maternal diet and risk of neural tube defects in Bangladesh
Authors: Obrycki John F. , Lee Jane J. , Kapur Kush , Paul Ligi , Hasan Md Omar Sharif Ibne , Mia Selim , Quamruzzaman Quazi , Christiani David C. , Mazumdar Maitreyi
Published: April 2019

Objectives

Mothers need a nutrient‐rich diet for healthy neural tube development. Neural tube defect risk can be reduced through fortifying grain products with folic acid and taking folic acid supplements. Fortification is not required in Bangladesh. Maternal supplement use rates are low, similar to other countries. This study evaluates maternal dietary intake during pregnancy to identify possible interventions.

Methods

A food frequency questionnaire (FFQ) assessed maternal diet. The primary aim compared dietary intake (calories, fat, carbohydrate, protein, fiber, vitamins, and minerals) between mothers of infants with myelomeningocele (cases) and mothers of controls. Secondary aims included (i) comparing foods consumed and (ii) evaluating if rice intake correlated with arsenic exposure. Pairedt‐tests, Wilcoxon signed rank tests, McNemar's chi‐squared test, and linear regression were used.

Results

This study included 110 matched mother–infant pairs (55 cases/55 controls). Mothers of cases and mothers of controls had similar caloric intake [median 2406 kcal/day vs. 2196 kcal/day (p = 0.071)]. Mothers in both groups consumed less than half the daily recommended 600 μg of folate. Diets were potentially deficient in vitamins A, D, E, potassium, sodium, and iron. Steamed rice was the primary food consumed for both groups, and this rice intake was not associated with toenail arsenic.

Conclusions

Dietary interventions should increase folate, vitamins A, D, E, potassium, sodium, and iron intake in Bangladeshi mothers. Folic acid fortification of grain products maybe the only viable strategy to achieve adequate folate intake for mothers. Given the central role of rice to the Bangladeshi diet, fortifying rice may be a viable option.
Determination of GL‐V9, a derivative of wogonin, in rat plasma by UPLC–MS/MS and its application to a pharmacokinetic study after oral and pulmonary administration
Authors: Xing Han , Ren Chang , Kong Ying , Ni Qi , Wang Zeyu , Zhao Di , Li Ning , Chen Xijing , Lu Yang
Published: April 2019

GL‐V9, a derivative of wogonin, shows much more potent anticancer properties than wogonin. In this study, a selective, sensitive and rapid ultra‐high‐performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) method was developed and validated for the determination of GL‐V9 in rat plasma. Plasma samples were processed using methanol to precipitate protein. Chromatographic separation of analytes was achieved on a C18 column using gradient elution within 4.5 min. The mobile phase consisted of acetonitrile and water including 0.1% (v/v) formic acid and 5 mm ammonium acetate. GL‐V9 and caffeine (internal standard) were monitored by positive electrospray triple quadrupole mass spectrometer and quantified using multiple reaction monitoring (MRM) mode with the transitions of m/z 410.20 → 126.10 (GL‐V9) and 195.10 → 138.00 (IS: caffeine), respectively. Good linearity was obtained over the range of 2–1000 ng/mL (R2 > 0.99) and the extraction recovery was 101.91 ± 11.34%. The intra‐ and inter‐day precision variations were small (RSD 1.35–6.96%) and the relative error (RE) of accuracy was −7.35–6.27%. The established and validated UPLC–MS/MS method was successfully applied to study the pharmacokinetic behavior of GL‐V9 after administration through different delivery routes. The results demonstrated that pulmonary delivery exhibited a greater advantage in terms of improving bioavailability compared with oral administration.
Assorted control charts: An efficient statistical approach to monitor pH values in ecotoxicology lab
Authors: Abbas Nasir , Saeed Usman , Riaz Muhammad
Published: April 2019

Primarily, three types of control charts are employed to observe the disturbances in the process parameters. The large shifts are detected efficiently by Shewhart's control chart, whereas for small and medium instabilities, cumulative sum and exponentially weighted moving average control charts are used. This study proposes an assorted approach to monitor small, medium, and large disturbances in a single control charting procedure. For the evaluation of the proposed assorted control chart, we have used various measures like average run length, standard deviation run length, extra quadratic loss, relative average run length, and performance comparison index. A comparison of the proposed assorted control chart is presented with some typical charts including the Shewhart, cumulative sum, exponentially weighted moving average control charts, and some advanced modification such as combined Shewhart‐EWMA (CSE), combined Shewhart‐CUSUM (CSC), mixed EWMA‐CUSUM (MEC), FIR EWMA, and adaptive EWMA (AEWMA). Finally, a real‐life application example is presented to monitor the pH level of water in an ecotoxicology lab.
Alloyed Tetranuclear Metal Chains of Pd4−nPtn (n=0–3) Scaffolded by a New Linear Tetraphosphine Containing a PNP Bridge
Authors: Tanase Tomoaki , Tanaka Miho , Hamada Mami , Morita Yuka , Nakamae Kanako , Ura Yasuyuki , Nakajima Takayuki
Published: April 2019

A new linear tetraphosphine containing a PNP phosphazane bridge, rac‐bis[(diphenylphosphinomethyl)phenylphosphino]phenylamine (rac‐dpmppan), was synthesized and utilized to support a series of Pd/Pt mixed metal tetranuclear chains, [Pd4−nPtn(μ‐rac‐dpmppan)2(XylNC)2](PF6)2 (XylNC=xylyl isocyanide; n=0: Pd4 (1), 1: PtPd3 (2), 2: PtPd2Pt (3), 2: Pt2Pd2 (4), 3: Pt2PdPt (5)), in which the number and positions of additional Pt atoms were successfully controlled depending on the respective synthetic procedures using transformations from 1 to 3 through 2 and from 4 to 5 by redox‐coupled exchange reactions. The 31P{1H} NMR and ESI mass spectra and X‐ray diffraction analyses revealed almost identical tetranuclear structures, with slight contraction of metal‐metal bonds according to incorporation of Pt atoms. The electronic absorption spectra of 1–5 exhibited characteristic bands at 635–510 nm with an energy propensity depending on the number and positions of Pt centres, which were assigned to HOMO (dσ*σσ*) to LUMO (dσ*σ*σ*) transition by theoretical calculations. The present results demonstrated that the electronic structures of Pd/Pt mixed‐metal tetranuclear complexes are finely tuned as orbital‐overlapping alloyed metal chains by atomically precise Pt incorporation in the Pd4 chain.
Simulation of unsteady blood flows in a patient‐specific compliant pulmonary artery with a highly parallel monolithically coupled fluid‐structure interaction algorithm
Authors: Kong Fande , Kheyfets Vitaly , Finol Ender , Cai Xiao‐Chuan
Published: April 2019

Computational fluid dynamics (CFD) is increasingly used to study blood flows in patient‐specific arteries for understanding certain cardiovascular diseases. The techniques work quite well for relatively simple problems but need improvements when the problems become harder when (a) the geometry becomes complex (eg, a few branches to a full pulmonary artery), (b) the model becomes more complex (eg, fluid‐only to coupled fluid‐structure interaction), (c) both the fluid and wall models become highly nonlinear, and (d) the computer on which we run the simulation is a supercomputer with tens of thousands of processor cores. To push the limit of CFD in all four fronts, in this paper, we develop and study a highly parallel algorithm for solving a monolithically coupled fluid‐structure system for the modeling of the interaction of the blood flow and the arterial wall. As a case study, we consider a patient‐specific, full size pulmonary artery obtained from computed tomography (CT) images, with an artificially added layer of wall with a fixed thickness. The fluid is modeled with a system of incompressible Navier‐Stokes equations, and the wall is modeled by a geometrically nonlinear elasticity equation. As far as we know, this is the first time the unsteady blood flow in a full pulmonary artery is simulated without assuming a rigid wall. The proposed numerical algorithm and software scale well beyond 10 000 processor cores on a supercomputer for solving the fluid‐structure interaction problem discretized with a stabilized finite element method in space and an implicit scheme in time involving hundreds of millions of unknowns.
Performance anomaly detection using isolation‐trees in heterogeneous workloads of web applications in computing clouds
Authors: Kardani‐Moghaddam Sara , Buyya Rajkumar , Ramamohanarao Kotagiri
Published: April 2019

Cloud computing is a model for on‐demand access to shared resources based on the pay‐per‐use policy. In order to efficiently manage the resources, a continuous analysis of the operational state of the system is required to be able to detect the performance degradations and malfunctioned resources as soon as possible. Every change in the workload, hardware condition, or software code can change the state of the system from normal to abnormal, which causes the performance and quality of service degradations. These changes or anomalies vary from a simple gradual increase in the load to flash crowds, hardware faults, software bugs, etc. In this paper, we propose Isolation‐Forest based anomaly detection (IFAD) framework based on the unsupervised Isolation technique for anomaly detection in a multi‐attribute space of performance indicators for web‐based applications. Unsupervised nature of the algorithm and its fast execution make this algorithm most suitable for the environments with dynamic nature where the patterns of data change frequently. The experiment results demonstrate that IFAD can achieve good detection accuracy especially in terms of precision for multiple types of the anomaly. Moreover, we show the importance of validating the accuracy of anomaly detection algorithms with regard to both Area Under the Curve (AUC) and Precision‐Recall AUC (PRAUC) in an extensive set of comparisons including multiple unsupervised algorithms. The demonstration of the effectiveness of each algorithm shown by PRAUC results indicates the importance of PRAUC in selecting suitable anomaly detection algorithm, which is largely ignored in the literature.
Self‐Assembly of a β‐Peptide Foldamer: The Role of the Surfactant in Three‐Dimensional Shape Selection
Authors: Gong Jintaek , Eom Taedaehyeong , Lee Wonchul , Roy Arup , Kwon Sunbum , Kim Hyungjun , Lee Hee‐Seung
Published: April 2019

The effect of a small ionic surfactant, cetyltrimethylammonium bromide (CTAB), on the self‐assembly of a β‐peptide has been systematically studied by using scanning electron microscopy, X‐ray diffraction, selected area electron diffraction, and molecular dynamics (MD) simulations. The latter study suggested that the formation of asymmetric microcrystals may be due to the preferential adsorption of CTAB on {011} and (001) crystal faces. This work provides a plausible rationale for the characteristic 3D morphogenesis of foldectures and elucidates the interaction between the surfactant and organic building block molecules.
Syntactic ambiguity resolution in dyslexia: An examination of cognitive factors underlying eye movement differences and comprehension failures
Authors: Stella Marianna , Engelhardt Paul E.
Published: April 2019

This study examined eye movements and comprehension of temporary syntactic ambiguities in individuals with dyslexia, as few studies have focused on sentence‐level comprehension in dyslexia. We tested 50 participants with dyslexia and 50 typically developing controls, in order to investigate (a) whether dyslexics have difficulty revising temporary syntactic misinterpretations and (b) underlying cognitive factors (i.e., working memory and processing speed) associated with eye movement differences and comprehension failures. In the sentence comprehension task, participants read subordinate‐main structures that were either ambiguous or unambiguous, and we also manipulated the type of verb contained in the subordinate clause (i.e., reflexive or optionally transitive). Results showed a main effect of group on comprehension, in which individuals with dyslexia showed poorer comprehension than typically developing readers. In addition, participants with dyslexia showed longer total reading times on the disambiguating region of syntactically ambiguous sentences. With respect to cognitive factors, working memory was more associated with group differences than was processing speed. Conclusions focus on sentence‐level syntactic processing issues in dyslexia (a previously under‐researched area) and the relationship between online and offline measures of syntactic ambiguity resolution.
Rapid assessment of coral cover from environmental DNA in Hawai'i
Authors: Nichols Patrick K. , Marko Peter B.
Published: April 2019

Coral reefs support the most diverse assemblages of marine life on Earth, yet are declining due to local and global stressors. Rapid and widespread monitoring is essential for tracking ecosystem responses, but assessment of coral communities traditionally relies on time‐consuming visual estimates of coral cover, the percentage of substrate occupied by living corals. The analysis of environmental DNA (eDNA) offers fast and efficient insights into the abundance and distribution of species, yet it remains untested to monitor coral biomass. Here, we demonstrate that visual estimates are highly correlated with the abundance of coral eDNA on reefs in Hawai'i measured with a relatively simple, rapid, but replicated PCR‐based metabarcoding approach. Target sequence length was also tested by amplifying short (~120 base‐pairs) and long (~400 base‐pairs) fragments from the same region of two mitochondrial DNA genes, 16S ribosomal DNA, and cytochrome oxidase‐1 using primers designed to preferentially amplify Hawaiian coral genera. Careful primer selection and target sequence lengths play an important role in determination of coral abundance from eDNA biomass. Given its broad applicability and ease of use, eDNA metabarcoding can provide complementary analytical support for biomonitoring programs and management initiatives tracking changes in coral cover caused by climate change and other disturbances on coral reefs.
Heart failure in cardiomyopathies: a position paper from the Heart Failure Association of the European Society of Cardiology
Authors: Seferović Petar M. , Polovina Marija , Bauersachs Johann , Arad Michael , Ben Gal Tuvia , Lund Lars H. , Felix Stephan B. , Arbustini Eloisa , Caforio Alida L.P. , Farmakis Dimitrios , Filippatos Gerasimos S. , Gialafos Elias , Kanjuh Vladimir , Krljanac Gordana , Limongelli Giuseppe , Linhart Aleš , Lyon Alexander R. , Maksimović Ružica , Miličić Davor , Milinković Ivan , Noutsias Michel , Oto Ali , Oto Öztekin , Pavlović Siniša U. , Piepoli Massimo F. , Ristić Arsen D. , Rosano Giuseppe M.C. , Seggewiss Hubert , Ašanin Milika , Seferović Jelena P. , Ruschitzka Frank , Čelutkiene Jelena , Jaarsma Tiny , Mueller Christian , Moura Brenda , Hill Loreena , Volterrani Maurizio , Lopatin Yuri , Metra Marco , Backs Johannes , Mullens Wilfried , Chioncel Ovidiu , de Boer Rudolf A. , Anker Stefan , Rapezzi Claudio , Coats Andrew J.S. , Tschöpe Carsten
Published: April 2019

Cardiomyopathies are a heterogeneous group of heart muscle diseases and an important cause of heart failure (HF). Current knowledge on incidence, pathophysiology and natural history of HF in cardiomyopathies is limited, and distinct features of their therapeutic responses have not been systematically addressed. Therefore, this position paper focuses on epidemiology, pathophysiology, natural history and latest developments in treatment of HF in patients with dilated (DCM), hypertrophic (HCM) and restrictive (RCM) cardiomyopathies. In DCM, HF with reduced ejection fraction (HFrEF) has high incidence and prevalence and represents the most frequent cause of death, despite improvements in treatment. In addition, advanced HF in DCM is one of the leading indications for heart transplantation. In HCM, HF with preserved ejection (HFpEF) affects most patients with obstructive, and ∼10% of patients with non‐obstructive HCM. A timely treatment is important, since development of advanced HF, although rare in HCM, portends a poor prognosis. In RCM, HFpEF is common, while HFrEF occurs later and more frequently in amyloidosis or iron overload/haemochromatosis. Irrespective of RCM aetiology, HF is a harbinger of a poor outcome. Recent advances in our understanding of the mechanisms underlying the development of HF in cardiomyopathies have significant implications for therapeutic decision‐making. In addition, new aetiology‐specific treatment options (e.g. enzyme replacement therapy, transthyretin stabilizers, immunoadsorption, immunotherapy, etc.) have shown a potential to improve outcomes. Still, causative therapies of many cardiomyopathies are lacking, highlighting the need for the development of effective strategies to prevent and treat HF in cardiomyopathies.