bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic simulation and experimental verification of foam transport in porous media based on level set method
Authors: Zhang Chao , Wang Fei , Li Zhaomin , Chen Hailong
Published: June 2019

The properties of the foam fluid in porous media depend on its dynamic structure. However, few studies have focused on the dynamic structural change in foam. In this research, a method based on the level set method is proposed for the simulation of aqueous foam transport in porous media. As a first step, we focus on the Jamin effect, and a concise relation is established which reveals that the resultant pressure is proportional to the capillary pressure. Second, the snap‐off process of foam in porous media is studied, and both the two stages, including partial disintegration, are revealed based on the results. Third, the conclusion that foam automatically selects a larger channel in which to continue flowing is obtained by studying the foam selectivity. Finally, experiments are carried out to verify the simulation results using different models. The simulation results are in good agreement with the experimental results. These results are expected to be helpful for further understanding the foam characteristics and their effective applications.
Modeling and forecasting commodity market volatility with long‐term economic and financial variables
Authors: Nguyen Duc Khuong , Walther Thomas
Published: June 2019

This paper investigates the time‐varying volatility patterns of some major commodities as well as the potential factors that drive their long‐term volatility component. For this purpose, we make use of a recently proposed generalized autoregressive conditional heteroskedasticity–mixed data sampling approach, which typically allows us to examine the role of economic and financial variables of different frequencies. Using commodity futures for Crude Oil (WTI and Brent), Gold, Silver and Platinum, as well as a commodity index, our results show the necessity for disentangling the short‐term and long‐term components in modeling and forecasting commodity volatility. They also indicate that the long‐term volatility of most commodity futures is significantly driven by the level of global real economic activity as well as changes in consumer sentiment, industrial production, and economic policy uncertainty. However, the forecasting results are not alike across commodity futures as no single model fits all commodities.
Issues in assessing the health risks of n‐butanol
Authors: Segal Deborah , Bale Ambuja S. , Phillips Linda J. , Sasso Alan , Schlosser Paul M. , Starkey C. , Makris Susan L.
Published: June 2019

A literature review and health effects evaluation were conducted for n‐butanol, a chemical that occurs naturally in some foods, which is an intermediate in the production of butyl esters and can be used as a gasoline additive or blend. Studies evaluating n‐butyl acetate were included in the review as n‐butyl acetate is rapidly converted to n‐butanol following multiple routes of exposure. The primary n‐butanol health effects identified were developmental and nervous system endpoints. In conducting the literature review and evaluating study findings, the following observations were made: (1) developmental findings were consistently identified; (2) neurodevelopmental findings were inconsistent; (3) evidence for nervous system effects was weak; (4) comparing internal doses from oral and inhalation exposures using physiologically based pharmacokinetic models introduces uncertainties; and (5) a lack of mechanistic information for n‐butanol resulted in the reliance on mechanistic data for ethanol, which may or may not be applicable to n‐butanol. This paper presents findings from a literature review on the health effects of n‐butanol and proposes research to help reduce uncertainty that exists due to database limitations.
Prokaryotic SPHINX replication sequences are conserved in mammalian brain and participate in neurodegeneration
Authors: Szigeti‐Buck Klara , Manuelidis Laura
Published: June 2019

A new class of viral mammalian Slow Progressive Hidden INfections of variable (X) latency (“SPHINX”) DNAs, represented by the 1.8 and 2.4 kb nuclease‐protected circular elements, were discovered in highly infectious cytoplasmic particles isolated from Creutzfeldt‐Jakob Disease (CJD) and scrapie samples. These DNAs contained replication initiation sequences (REPs) with approximately 70% homology to those of environmental Acinetobacter phage. Antibodies against REP peptides from the 1.8 kb DNA highlighted a 41 kDa protein (spx) on Western blots, and in situ studies previously revealed its peripheral tissue expression, for example, in pancreatic islet cells, keratinocytes, kidney tubules, and oocytes but not pancreatic exocrine cells, alveoli, and striated muscle. To determine if spx concentrated in specific neurons and synapses, and also maintained a conserved pattern of architectural organization in mammalian brains, we evaluated mouse, rat, hamster, guinea pig (GP), and human samples. Most outstanding was the cross‐species concentration of spx in huge excitatory synapses of mossy fibers and small internal granule neuron synapses, the only excitatory neuron within the cerebellum. Spx also localized to excitatory glutamate type synapses in the hippocampus, and both cerebellar and hippocampal synaptic spx was demonstrable ultrastructurally. Studies of two well‐characterized models of sporadic CJD (sCJD) revealed novel spx pathology. Vacuolar loss of cerebellar synaptic complexes, thinning of the internal granule cell layer, and fibrillar spx accumulations within Purkinje neurons were prominent in sCJD GP brains. In rats, comparable spx fibrillar changes appeared in hippocampal pyramidal neurons, and they preceded prion protein misfolding. Hence, spx is an integral player in progressive neurodegeneration. The evolutionary origin, spread, and neuropathology of SPHINX 1.8 REP sequences opens another unanticipated chapter for mammalian symbiotic interactions with environmental microbes.
Sulforaphane administration alleviates diffuse axonal injury (DAI) via regulation signaling pathway of NRF2 and HO‐1
Authors: Wu Dong‐Mei , Zheng Zi‐Hui , Fan Shao‐Hua , Zhang Zi‐Feng , Chen Gui‐Quan , Lu Jun
Published: June 2019

Background

Nuclear factor erythroid 2‐related factor 2 (Nrf2) can alleviate diffuse axonal injury (DAI)‐induced apoptosis by regulating expression of heme oxygenase‐1 (HO‐1), while sulforaphane (SFN) was shown to reduce oxidative stress by increasing the expression of Nrf2. Therefore, we aimed to investigate therapeutic effect of SFN in the treatment of DAI and the ability of SFN to reduce oxidative stress.

Methods

The 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide (MTT) assay was used to observe the effects of H2O
2 and SFN on cell viability. Fluorometric assay, Western blot analysis, and flow cytometry were conducted to validate the protective role of SFN in an animal model of DAI. In addition, the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were measured in DAI rats treated by SFN, while Western blot, immunohistochemistry assay, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay were carried out to verify the effect of SFN in different animal groups.

Results

Cell viability was reduced by H2O
2 in a dose‐dependent manner, while the treatment by SFN significantly promoted cell growth. Meanwhile the administration of SFN effectively reduced the levels of caspase‐3/poly(ADP‐ribose) polymerase (PARP) activity increased by the H
2O
2 treatment, indicating that the protective effect of SFN could be mediated by its ability to suppress caspase‐3 activation and PARP cleavage. In addition, the SFN treatment reduced the intracellular reactive oxygen species (ROS) generation induced by H
2O
2. Moreover, the MDA levels of SOD/GPx activity in various rat groups showed the protective effects of SFN in DAI rats. It is suspected that the protective effect of SFN was exerted via the activation of the Nrf2/HO‐1 signaling pathway. In this study, DAI and DAI + phosphate‐buffered saline (PBS) groups also showed the presence of more TUNEL‐positive cells compared with the sham‐operated group, while the SFN treatment reduced the extent of neuronal apoptosis.

Conclusions

By activating the Nrf2/HO‐1 signaling pathway and reducing the activity of caspase‐3, SFN reduces the apoptosis of neurons in brain trauma‐induced DAI.
Green synthesis of bis‐coumarin derivatives using Fe(SD)3as a catalyst and investigation of their biological activities
Authors: Mahmoodi Nosrat O. , Jalalifard Zeinab , Fathanbari Ghanbari Pirbasti
Published: June 2019

A convenient, practical, green, and environmentally friendly method was developed for the synthesis of biscoumarins and corresponding tetrakis products from the reaction of 4‐hydroxycoumarin and various aldehydes. The bis‐coumarins were synthesized in high yield under mild reaction conditions. Products were obtained in the presence of in situ prepared Fe(SD)3[Iron(III) dodecyl sulfate] as a combined Lewis acid–surfactant catalyst (LASC) in water in short reaction times. Also, the antibacterial activity of compounds was screened againstPseudomonas aeruginosaandEscherichia colias Gram‐negative bacteria andMicrococcus luteusandStaphylococcus aureusas Gram‐positive bacterial strains. Products3g,3k–lwere most active than cefotaxime againstE. coliand also compounds3cand3gwere most active than cefotaxime againstS. aureus.
Inhibition of microRNA‐103 attenuates inflammation and endoplasmic reticulum stress in atherosclerosis through disrupting the PTEN‐mediated MAPK signaling
Authors: Jiang Li , Qiao Yanguo , Wang Zhenghui , Ma Xiuzhu , Wang Haichao , Li Jian
Published: June 2019

Atherosclerosis (AS), a chronic disorder of large arteries, is the underlying pathological process of heart disease and stroke. Former researchers have found that microRNAs (miRs) are involved in the several key processes of AS. Apolipoprotein E knockout (ApoE−/−) mice fed a high‐fat‐diet (HFD) to establish AS model. The expression of miR‐103 was characterized in the mice model. The effects of miR‐103 on inflammation and endoplasmic reticulum stress (ERS) were analyzed when the expression of miR‐103 was inhibited in ApoE
−/− mice fed an HFD and human aortic endothelial cells (HAECs) exposed to oxidized low‐density lipoprotein (ox‐LDL). The relationship between miR‐103 and phosphatase and tensin homolog (PTEN) was identified by luciferase activity detection and real‐time quantitative polymerase chain reaction (RT‐qPCR). Gain‐ and loss‐function approaches were further applied for investigating the regulatory effects of miR‐103 and PTEN on ERS. Role of MAPK signaling was then analyzed using PD98059 to block this pathway. miR‐103 was highly expressed in the ApoEApoE
−/− mice fed an HFD. Downregulation of miR‐103 suppressed inflammation and ERS in endothelial cells isolated from ApoE
−/− mice fed a HFD and ox‐LDL‐exposed HAECs. In addition, miR‐103 can target PTEN and downregulate its expression. Overexpression of PTEN reversed the miR‐103‐induced activation of MAPK signaling. Moreover, PTEN upregulation or MAPK signaling inhibition ease miR‐103‐induced inflammation and ERS in vivo and in vitro. Thus, miR‐103 depletion restrains the progression of AS through blocking PTEN‐mediated MAPK signaling.
Dysregulated N6‐methyladenosine methylation writer METTL3 contributes to the proliferation and migration of gastric cancer
Authors: Liu Tong , Yang Sheng , Sui Jing , Xu Si‐Yi , Cheng Yan‐ping , Shen Bo , Zhang Yan , Zhang Xiao‐mei , Yin Li‐hong , Pu Yue‐pu , Liang Ge‐yu
Published: June 2019

Accumulating evidence implies that N6‐methyladenosine (m6A) methylation participated in the tumorigenesis of gastric cancer (GC). Here we synthetically analyzing the prognostic value and expression profile of seven m6A methylation‐relevant genes through silico analysis of sequencing data downloaded from The Cancer Genome Atlas, Kaplan–Meier plotter, and Gene Expression Omnibus database. We explored the methyltransferase‐like 3 (METTL3) expression in GC cell line and tumor tissues by reverse transcription quantitative polymerase chain reaction and western blot analysis. The m6A methylation status of total RNA was measured by m6A RNA methylation quantification kit. Small interfering RNA was used to establish METTL3 knockdown cell lines. We also measure the proliferation and migration capability GC cell. Furthermore, we detect the epithelial cell mesenchymal transition marker and m6A methylation level after METTL3 knock down. Our result revealed that METTL3 was significantly increased in GC tissues compared with control in big crowd data sets. Survival analysis showed that METTL3 serve as a poor prognostic factor for GC patients. The expression level of METTL3 gradually increased with the progress of tumor stage and grade. GFI1 is an important transcription factor associated with METTL3. We verified the up‐trend of METTL3 in messenger RNA and protein expression and observed a significant increase in the m6A methylation status of total RNA in the GC cells and tissues. METTL3 knockdown inhibited total RNA m6A methylation level, as well as cell proliferation and migration capacity. Moreover, METTL3 knockdown decreased α‐smooth muscle actin. Taken together, our finding revealed that m6A methylation writer METTL3 serve as an oncogene in tumorigenesis of GC.
DJ‐1 regulates tyrosine hydroxylase expression through CaMKKβ/CaMKIV/CREB1 pathway in vitro and in vivo
Authors: Xu Xingyun , Wang Rui , Hao Zongbing , Wang Guanghui , Mu Chenchen , Ding Jianqing , Sun Wanping , Ren Haigang
Published: June 2019

Lack of dopamine production and neurodegeneration of dopaminergic neurons in the substantia nigra are considered as the major characteristics of Parkinson's disease, a prevalent movement disorder worldwide. DJ‐1 mutation leading to loss of its protein functions is a genetic factor of PD. In this study, our results illustrated that DJ‐1 can directly interact with Ca2+/calmodulin‐dependent protein kinase kinase β (CaMKKβ) and modifies the cAMP‐responsive element binding protein 1 (CREB1) activity, thus regulates tyrosine hydroxylase (TH) expression. In Dj‐1 knockout mouse substantia nigra, the levels of TH and the phosphorylation of CREB1 Ser133 are significantly decreased. Moreover, Dj‐1 deficiency suppresses the phosphorylation of CaMKIV (Thr196/200) and CREB1 (Ser133), subsequently inhibits TH expression in vitro. Furthermore, Knockdown of Creb1 abolishes the effects of DJ‐1 on TH regulation. Our data reveal a novel pathway in which DJ‐1 regulates CaMKKβ/CaMKIV/CREB1 activities to facilitate TH expression.
Characterization and tentative identification of new flunitrazepam metabolites in authentic human urine specimens using liquid chromatography‐Q exactive‐HF hybrid quadrupole‐Orbitrap‐mass spectrometry (LC‐QE‐HF‐MS)
Authors: Qin Shiyang , Xin Guobin , Wang Yuanfeng , Qiao Jing , Zhang Wenfang , Xu Duoqi , Xu Zizhen , Liu Yongtao , Zhang Ying , Lu Jianghai
Published: June 2019

Flunitrazepam (FNZ) is a potent hypnotic, sedative, and amnestic drug used to treat severe insomnia. In our recent study, FNZ metabolic profiles were investigated carefully. Six authentic human urine samples were purified using solid phase extraction (SPE) without enzymatic hydrolysis, and urine extracts were then analyzed by liquid chromatography‐Q exactive‐HF hybrid quadrupole‐Orbitrap‐mass spectrometry (LC‐QE‐HF‐MS), using the full scan positive ion mode and targeted MS/MS (ddms2) technique to make accurate mass measurements. There were 25 metabolites, including 13 phase I and 12 phase II metabolites, which were detected and tentatively identified by LC‐QE‐HF‐MS. In addition, nine previously unreported phase II glucuronide conjugates and four phase I metabolites are reported here for the first time. Eight metabolic pathways, including N‐reduction and O‐reduction, N‐glucuronidation, O‐glucuronidation, mono‐hydroxylation and di‐hydroxylation, demethylation, acetylation, and combinations, were implicated in this work, and 2‐O‐reduction together with dihydroxylation were two novel metabolic pathways for FNZ that were identified tentatively. Although 7‐amino FNZ is widely considered to be the primary metabolite, a previously unreported metabolites (M12) can also serve as a potential biomarker for FNZ misuse.
Exploring two contrasting surface‐active exopolysaccharides from a single strain of Ochrobactrum utilizing different hydrocarbon substrates
Authors: Sengupta Dipanjan , Datta Sriparna , Biswas Dipa
Published: June 2019

During production and characterization of exopolysaccharides (EPS) of Ochrobactrum pseudintermedium C1, it was observed that an experimental change in the basic hydrocarbon type of substrate for bacterial utilization led to elicitation of different surface‐active properties in the EPS produced. In the sugar substrate, it elicited surfactant property, while in oil substrates it elicited emulsifying property, which indicated that the EPS might be different. Consequently, attention was focused on a detailed analysis of this substrate‐specific EPS. Utilizing waste sugar, edible, and mineral oil substrates, EPS produced in each situation was characterized. Besides estimating surface activity and thermostability, each substrate‐specific EPS was analyzed by Fourier‐transform infrared spectroscopy, gas chromatography‐mass spectroscopy, 1H‐nuclear magnetic resonance, and matrix‐assisted laser desorption/ionization—time of flight mass spectroscopy to find any structural difference. The results were significantly contrasting although the similarity in molecular mass suggested a basic similarity in polysaccharide structure. Morphological differences were also evident both macroscopically and microscopically with scanning electron microscopy. As the surface‐active property of EPS was dependent on the substrate utilized, their structural differences might account for it. These diverse surface activities of EPS produced by a single bacterial strain simply by changing the nature of substrate would also augment their bioapplications. Moreover, utilization of waste and easily available substrates should make such applications convenient, ecofriendly, and cost‐worthy.
Non‐Invasive Ultrasound Quantification of Scar Tissue Volume Identifies Early Functional Changes During Tendon Healing
Authors: Ackerman Jessica E. , Studentsova Valentina , Myers Marlin , Buckley Mark R. , Richards Michael S. , Loiselle Alayna E.
Published: June 2019

Tendon injuries are very common and disrupt the transmission of forces from muscle to bone, leading to impaired function and quality of life. Successful restoration of tendon function after injury is a challenging clinical problem due to the pathological, scar‐mediated manner in which the tendons heal. Currently, there are no standard treatments to modulate scar tissue formation and improve tendon healing. A major limitation to the identification of therapeutic candidates has been the reliance on terminal endpoint metrics of healing in pre‐clinical studies, which require a large number of animals and result in destruction of the tissue. To address this limitation, we have identified quantification of scar tissue volume (STV) from ultrasound (US) imaging as a longitudinal, non‐invasive metric of tendon healing. STV was strongly correlated with established endpoint metrics of gliding function including gliding resistance and metatarsophalangeal (MTP) flexion angle. However, no associations were observed between STV and structural or material properties. To define the sensitivity of STV to identify differences between functionally discrete tendon healing phenotypes, we utilized S100a4 haploinsufficient mice (S100a4GFP/+), which heal with improved gliding function relative to wild‐type (WT) littermates. A significant decrease in STV was observed in S100a4GFP/+ repairs, relative to WT at day 14. Taken together, these data suggest US quantification of STV as a means to facilitate the rapid screening of biological and pharmacological interventions to improve tendon healing, and identify promising therapeutic targets, in an efficient, cost‐effective manner. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2476–2485, 2019
Plasma Citrulline Concentrations in Neonates With or Without Gastrointestinal Disease During Periods of Parenteral and Enteral Nutrition
Authors: Herrera Oscar R. , Talati Ajay J. , Helms Richard A.
Published: June 2019

Introduction

Citrulline is synthesized primarily in enterocytes. Retrospective work revealed higher plasma concentrations in patients without gastrointestinal (GI) disease than in those with GI disease, regardless of bowel resection, leading us to speculate whether it could be used as a marker of gut function prospectively. Our purpose was to analyze plasma citrulline in these patients, comparing a period of exclusive parenteral nutrition (PN) vs both PN and enteral nutrition (PN/EN).

Methods

Premature neonates were included in this study. Plasma samples were collected during 2 periods, PN and PN/EN. They were classified into groups: patients without GI disease (Group 1), patients with GI disease without resection (Group 2), and patients with GI disease and resection (Group 3). Plasma was analyzed by high‐performance liquid chromatography and tandem mass spectrometry (LC‐MS/MS). Data were described as median with ranges.

Results

Fifty patients were recruited for this study, from which 164 samples were obtained and analyzed by LC‐MS. Median plasma citrulline concentrations were 12.3 (5.6–39.4) µmol/L, 14.9 (6.8–39.8) µmol/L, and 10.8 (2.0–23.6) µmol/L for Groups 1, 2, and 3, respectively. After Bonferroni correction, only Group 3 had a significantly different median from the others. No differences were observed within periods of nutrition (PN vs PN/EN). Postconceptual age (PCA), among others, was assessed to determine differences for which the former demonstrated significance.

Conclusion

Premature neonates with bowel resection had lower plasma citrulline concentrations, confirming its role as gut mass marker, though without differences during transitional feeding. PCA may affect expression of this protein.
Meta‐analysis of full ROC curves: Additional flexibility by using semiparametric distributions of diagnostic test values
Authors: Hoyer Annika , Kuss Oliver
Published: June 2019

Diagnostic test accuracy studies frequently report on sensitivities and specificities for more than one threshold of the diagnostic test under study. Although it is obvious that the information from all thresholds should be used for a meta‐analysis, in practice, frequently, only a single pair of sensitivity and specificity is selected. To overcome this disadvantage, we recently proposed a statistical model for the meta‐analysis of such full receiver operating characteristic (ROC) curves that uses the relationship between a ROC curve and a bivariate model for interval‐censored data. In this model, diagnostic tests values reported by the single studies were assumed to follow a parametric distribution. We propose a generalization of this model that allows for a flexible semiparametric modelling of the underlying distribution of the diagnostic test values by using the idea of piecewise constant hazard modelling. We show the results of a simulation study that indicates that the approach works reasonably well in practice. Finally, we illustrate the model by the example of population‐based screening for type 2 diabetes mellitus.
Changes in the extent and distribution of urban land cover in the Democratic People's Republic of Korea (North Korea) between 1987 and 2010
Authors: Kang Sangjun , Choi Jinmu , Yoon Hyejin , Choi Woonsup
Published: June 2019

Largely due to data unavailability, the spatial pattern of urban growth in North Korea has been rarely studied. This study explored urban changes in North Korea and provided their plausible causes. The present study used satellite‐based land cover data sets produced by the government of South Korea to examine the extent and distribution of urban land cover in North Korea between the late 1980s (1987–1989) and late 2000s (2008–2010) at the municipal level. The urban expansion intensity index (UEII) was calculated for two 10‐year intervals, and the spatial autocorrelation of UEII values was examined. Major findings from the study are summarized as follows: (a) the capital city Pyongyang's dominance continued without any obvious sign of slowing down, (b) economic development districts do not appear to have much influence on urban land cover changes, and (c) the extent of urban land cover slightly decreased in much of the country between the late 1990s (1997–1999) and late 2000s (2008–2010). The results and discussion in this study suggest internal migration and stagnant economy as probably important causes for the phenomena.
Genetic link to schizophrenia ‘greatly’ overestimated, more research urged
Authors: Canady Valerie A.
Published: June 2019

A new study published in Psychiatry Research examining the limitations of genetic research studies on schizophrenia suggests that researchers have greatly overestimated schizophrenia as being primarily a genetic disease. Future research should focus on the nongenetic aspects, the authors say.
Robust pCASL perfusion imaging using a 3D Cartesian acquisition with spiral profile reordering (CASPR)
Authors: Greer Joshua S. , Wang Xinzeng , Wang Yiming , Pinho Marco C. , Maldjian Joseph A. , Pedrosa Ivan , Madhuranthakam Ananth J.
Published: June 2019

Purpose

To improve the robustness of arterial spin‐labeled measured perfusion using a novel Cartesian acquisition with spiral profile reordering (CASPR) 3D turbo spin echo (TSE) in the brain and kidneys.

Methods

The CASPR view ordering followed a pseudo‐spiral trajectory on a Cartesian grid, by sampling the center of k‐space at the beginning of each echo train of a segmented 3D TSE acquisition. With institutional review board approval and written informed consent, 14 normal subjects (9 brain and 5 kidneys) were scanned with pCASL perfusion imaging using 3D CASPR and compared against 3D linear TSE (brain and kidneys), the established 2D EPI and 3D gradient and spin echo perfusion (brain), and 2D single‐shot turbo spin‐echo perfusion (kidneys). The SNR and the quantitative perfusion values were compared among different acquisitions.

Results

3D CASPR TSE achieved robust perfusion across all slices compared to 3D linear TSE in the brain and kidneys. Compared to 2D EPI, 3D CASPR TSE showed higher SNR across the brain (P < 0.01), and exhibited good agreement (36.4 ± 4.7 and 36.9 ± 5.3 mL/100 g/min with 2D EPI and 3D CASPR, respectively), and with 3D gradient and spin echo (27.9 ± 7.2 mL/100 g/min). Compared to a single slice 2D single‐shot turbo spin‐echo acquisition, 3D CASPR TSE achieved robust perfusion across the entire kidneys in similar scan time with comparable quantified perfusion values (154.1 ± 74.6 and 151.7 ± 70.6 mL/100 g/min with 2D single‐shot turbo spin‐echo and 3D CASPR, respectively).

Conclusion

The CASPR view ordering with 3D TSE achieves robust arterial spin‐labeled perfusion in the brain and kidneys because of the sampling of the center of k‐space at the beginning of each echo train.
Numerical modeling of rock failure under dynamic loading with polygonal elements
Authors: Saksala Timo , Jabareen Mahmood
Published: June 2019

Polygonal finite elements are gaining an increasing attention in the computational mechanics literature, but their application in rock mechanics is very rare. This paper deals with numerical modeling of rock failure under dynamic loading based on polygonal finite elements. For this end, a damage‐viscoplastic constitutive model for rock based on the Mohr‐Coulomb criterion with the Rankine criterion as a tensile cutoff is employed and implemented with the polygonal finite element method. Moreover, the mineral mesostructure or rock is described by randomly mapping groups of polygonal elements representing the constituent minerals into a global mesh and assigning these groups with the corresponding mineral material properties. The performance of the polygonal elements is compared with that of the linear and quadratic triangular and bilinear quadrilateral elements in numerical simulations of controlled shear band formation under uniaxial compression and lateral splitting failure in the dogbone tension test. Numerical simulations of uniaxial tension and compression tests as well as dynamic Brazilian disc test under increasing loading rates demonstrate that the present approach predicts the correct failure modes as well as the dynamic increase in strength of rock.
Development of Obesity Competencies for Medical Education: A Report from the Obesity Medicine Education Collaborative
Authors: Kushner Robert F. , Horn Deborah B. , Butsch W. Scott , Brown Joshua D. , Duncan Katherine , Fugate Colony S. , Gorney Carol , Grunvald Eduardo L. , Igel Leon I. , Pasarica Magdalena , Pennings Nicholas , Soleymani Taraneh , Velazquez Amanda
Published: June 2019

Objective

Obesity Medicine Education Collaborative (OMEC) was formed to develop obesity‐focused competencies and benchmarks that can be used by undergraduate and graduate medical education program directors. This article describes the developmental process used to create the competencies.

Methods

Fifteen professional organizations with an interest in obesity collaborated to form OMEC. Using the six Core Competencies of the Accreditation Council for Graduate Medical Education as domains and as a guiding framework, a total of 36 group members collaborated by in‐person meetings, email exchange, and conference calls. An iterative process was used by each working subgroup to develop the competencies and assessment benchmarks. The initial work was subsequently externally reviewed by 19 professional organizations.

Results

Thirty‐two competencies were developed across the six domains. Each competency contains five descriptive measurement benchmarks for evaluator rating.

Conclusions

This set of OMEC obesity‐focused competencies is the first evaluation tool developed to be used within undergraduate and graduate medical training programs for both formative and summative assessments. Routine and more robust assessment is expected to increase the competence of health care providers to assess, prevent, and treat obesity. In addition to dissemination, the competencies and benchmarks will need to undergo evaluation for further validity and practicality.
Maternal BMI‐Increasing Genetic Risk Score and Fetal Weights among Diverse US Ethnic Groups
Authors: Shrestha Deepika , Rahman Mohammad L. , Hinkle Stefanie N. , Workalemahu Tsegaselassie , Tekola‐Ayele Fasil
Published: June 2019

Objective

Associations between maternal genetic risk for obesity and fetal weight were examined at the end of the first (13 weeks 6 days), second (27 weeks 6 days), and third (40 weeks 0 days) trimesters of pregnancy among four race/ethnic groups in the US.

Methods

For 603 white, 591 black, 535 Hispanic, and 216 Asian women, maternal genetic risk score (GRS) was calculated as the sum of 189 BMI‐increasing alleles and was categorized into high or low GRS. Associations between GRS (continuous and categorical) and estimated fetal weight were tested overall and stratified by prepregnancy BMI, gestational weight gain (GWG), and fetal sex.

Results

High GRS compared with low GRS was associated with increased fetal weight at the end of the second (β: 22.7 g; 95% CI: 2.4‐43.1; P = 0.03) and third trimesters (β: 88.3 g; 95% CI: 9.0‐167.6; P = 0.03) among Hispanic women. The effect of GRS was stronger among Hispanic women with normal prepregnancy weight, adequate first trimester GWG, or inadequate second trimester GWG (P < 0.05). Among Asian women, high GRS was associated with increased weight among male fetuses but decreased weight among female fetuses (P < 0.05).

Conclusions

Maternal obesity genetic risk was associated with fetal weight with potential effect modifications by maternal prepregnancy BMI, GWG, and fetal sex.
Molecular pathology of the luminal class of urothelial tumors
Authors: Bernardo Carina , Eriksson Pontus , Marzouka Nour‐al‐dain , Liedberg Fredrik , Sjödahl Gottfrid , Höglund Mattias
Published: June 2019

Molecular subtypes of urothelial carcinoma may be divided into luminal and nonluminal tumors. Nonluminal tumors are composed of cases with basal/squamous‐like or small cell/neuroendocrine features, with a consensus on the molecular characteristics of the respective subtype. In contrast, luminal tumors are more disparate with three to five suggested subtypes and with definitions that do not always cohere. To resolve some of these disparities we assembled a cohort of 344 luminal tumors classified as urothelial‐like (Uro), with the subtypes UroA, UroAp, UroB, and UroC, or genomically unstable (GU) according to the LundTax system. Cases were systematically analyzed by immunohistochemistry using antibodies for proteins representing important biological processes or cellular states: KRT5, EGFR, and CDH3 for the integrity of a basal cell layer; CCNB1, Ki67, and FOXM1 for proliferation; FGFR3 and ERBB2 for receptor tyrosine kinase status; CCND1, CDKN2A(p16), RB1, and E2F3 for cell cycle regulation; PPARG, GATA3, and TP63 for the differentiation regulatory system; and KRT20 and UPK3 for the differentiation readout. We show that Uro tumors form one, albeit heterogenous, group characterized by FGFR3, CCND1, and RB1 expression, but low or absence of CDKN2A(p16) and ERBB2 expression. The opposite expression pattern is observed in GU cases. Furthermore, Uro tumors are distinguished from GU tumors by showing a high RB1/p16 expression ratio. Class defining characteristics were independent of pathological stage and growth pattern, and thus intrinsic. In Uro tumors, proliferation was limited to a well‐defined single layer of basal‐like cells in UroA tumors but occurred throughout the tumor parenchyma, independent of the basal layer, in the more progressed UroAp and UroC tumors. A similar change in proliferation topology was not observed in GU. We conclude that luminal urothelial carcinomas consist, at the molecular pathology level, of two major subtypes, the larger heterogenous Uro and the biologically distinct GU subtype. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Estimates for material shrinkage in molded parts caused by time‐varying cavity pressures
Authors: Bushko Wit C. , Stokes Vijay K.
Published: June 2019

The phenomenology of shrinkage is established through injection molding experiments in which shrinkage was measured at 25‐mm intervals along the length and width of rectangular plaques, molded in an instrumented mold. A simple solidification model, which assumes the solidified material to be elastic, is developed for the effect of time‐varying temperature and pressure histories on part shrinkage. This model predicts a linear dependence of shrinkage on an “effective pressure,” which combines the thermal diffusivity of the material, the wall thickness, and the time‐varying cavity pressure into a single parameter that is uniquely related to the shrinkage. The effective pressure is shown to effectively correlate in‐plane shrinkage data. The solidification model characterizes two material parameters, which can be estimated from the pressure‐volume‐temperature (PVT) diagram for the material, that describe the sensitivity of the shrinkage to the local cavity pressure history. The residual stresses predicted by this model are rather crude. POLYM. ENG. SCI., 59:1648–1656 2019. © 2019 Society of Plastics Engineers
Tough and recoverable triple‐network hydrogels based on multiple pairs of toughing mechanisms with excellent ionic conductivity as stable strain sensors
Authors: Li Shuai , Bu Ximan , Wu Linlin , Ma Xiaofeng , Diao Wenjing , Zhuang Zhenzhen , Zhou Yongmin
Published: June 2019

The emerging applications of hydrogels in flexible devices require it possess multifunctional properties including stable mechanical and functions under various deformations or external environments. Herein, a multifunctional polyvinyl alcohol/M‐alginate/PAM hydrogel with very excellent mechanical properties and sensing functions was fabricated by introducing multiple pairs of toughing mechanisms into triple network (TN). The multiple supramolecular physical networks work as sacrificial networks to toughen the materials when hydrogel deforms. The broken bonds can reform upon unloading endowing the recovery of hydrogels' properties and functions with the assistance of the elastic covalent network. The optimal TN hydrogels are extremely tough (a fracture strength of 512 kPa, a fracture toughness of 3 MJ/m3) and recoverable from fatigue damage (~77% toughness recovery after 5 min resting at room temperature). The presence of abundant ionic species endows the tough and recoverable TN hydrogels high ionic conductivity and high sensitivity as strain sensors. Moreover, such TN hydrogels with multi‐bond crosslinking in three networks can potentially guarantee stable mechanical and sensor functions under various deformations or external environments compared to the DN candidates. This work provides a simple strategy for fabricating multifunctional hydrogels with high stability to fulfill its flexible devices applications. POLYM. ENG. SCI., 59:1657–1666 2019. © 2019 Society of Plastics Engineers
Upregulation of the Glutaminase II Pathway Contributes to Glutamate Production upon Glutaminase 1 Inhibition in Pancreatic Cancer
Authors: Udupa Sunag , Nguyen Stephanie , Hoang Giang , Nguyen Tu , Quinones Addison , Pham Khoa , Asaka Ryoichi , Nguyen Kiet , Zhang Cissy , Elgogary Amira , Jung Jin G. , Xu Qingguo , Fu Jie , Thomas Ajit G. , Tsukamoto Takashi , Hanes Justin , Slusher Barbara S. , Cooper Arthur J. L. , Le Anne
Published: June 2019

The targeting of glutamine metabolism specifically via pharmacological inhibition of glutaminase 1 (GLS1) has been translated into clinical trials as a novel therapy for several cancers. The results, though encouraging, show room for improvement in terms of tumor reduction. In this study, the glutaminase II pathway is found to be upregulated for glutamate production upon GLS1 inhibition in pancreatic tumors. Moreover, genetic suppression of glutamine transaminase K (GTK), a key enzyme of the glutaminase II pathway, leads to the complete inhibition of pancreatic tumorigenesis in vivo unveiling GTK as a new metabolic target for cancer therapy. These results suggest that current trials using GLS1 inhibition as a therapeutic approach targeting glutamine metabolism in cancer should take into account the upregulation of other metabolic pathways that can lead to glutamate production; one such pathway is the glutaminase II pathway via GTK.
A density functional theory study on the superacidity of sulfuric, fluorosulfuric, and triflic acid derivatives with two cyclopentadiene rings: ion pairs formation in the gas phase
Authors: Valadbeigi Younes , Vianello Robert
Published: June 2019

The gas phase acidity of organosulfuric acid derivatives with two cyclopentadiene rings replacing the doubly‐bonded oxygen atoms was computationally assessed using the B3LYP DFT functional and 6–311++G(d,p) basis set. Introduced five‐membered rings increased the acidity through the delocalization of the excess negative charge in conjugates bases and by providing positions to accommodate electron withdrawing substituents such as F and CN. The calculated enthalpies of deprotonation (∆Hacid) of polycyanated systems were as low as 227.8 to 263.2 kcal mol–1 indicating exceptional superacidity. Substitution of one OH moiety by F or CF3 groups offered additional acidifying effect by preventing prototropic tautomerism in the neutral acids that acts towards lowering the acidity. The designed systems spontaneously protonated H2O and NH3 in the gas phase and produced stable ion pair clusters.
Neurally adjusted ventilatory assist versus conventional ventilation in the pediatric population: Are there benefits?
Authors: Karikari Serwaa , Rausa Jacqueline , Flores Saul , Loomba Rohit S.
Published: June 2019

Introduction

Neurally‐adjusted ventilator assist (NAVA) is a relatively new form of ventilation in which the electrical activity of the diaphragm is sensed by a catheter. The amplitude of this electrical signal is then used to deliver an appropriately proportioned pressure supported breath to the patient. Due to the synchronous nature of the breaths and the patient‐adjusted nature of the support, NAVA has been shown to have benefits over conventional ventilation. Meta‐analyses were conducted of published pediatric studies to compare ventilatory endpoints between NAVA and conventional ventilation.

Methods

Studies comparing ventilatory parameters between NAVA and conventional ventilation in pediatric patients were identified. These studies were reviewed for appropriateness for inclusion and studies of only pediatric patients with data for similar endpoints between both arms were then pooled.

Results

Statistically significant differences were noted in asynchrony, peak inspiratory pressure (PIP), and oxygen saturation by pulse oximetry. Asynchrony was 17% lower with NAVA, PIP was 1.74 cmH20 lower with NAVA, and oxygen saturation was 1.1% greater with NAVA. There was no statistically significant difference in peak expiratory pressure, mean airway pressure, electrical diaphragmatic activity, respiratory rate, hydrogen ion concentration, partial pressure of oxygen, or partial pressure of carbon dioxide.

Conclusion

Statistically significant differences were noted in percent asynchrony, PIP, and oxygen saturation when comparing NAVA to conventional ventilation. These all tended to favor NAVA. Other than percent asynchrony, however, the other statistically significant findings were not clinically significant.
Systematic review of the effectiveness of Kinesio taping for children with brachial plexus injury
Authors: Hassan Basant Saiid , Abbass Mai Elsayed , Elshennawy Shorouk
Published: June 2019

Objective

The purpose of this systematic review was to investigate the effectiveness of Kinesio taping on upper limb motor function in children with brachial plexus injury.

Data sources

Articles were identified through searches of the following databases: OVID, Web of Science, Science Direct, PubMed, Google Scholar, and the Cochrane library.

Methods

Studies were excluded if they were nonpeer‐reviewed publications, opinion articles, or not reported in English. The methodological quality of the studies was assessed using the Methodological Index for Nonrandomized Studies.

Results

Five studies met our inclusion criteria. Two studies were included in the meta‐analysis. A significant change was limited only to scapulothoracic internal rotation in three positions.

Conclusions

Adding Kinesio taping to the physical therapy programme to manage children with brachial plexus injury is still questionable and may help functional improvement. However, this improvement may be limited depending on the technique or mode of application.
Access and concentrations of atorvastatin in the prostate in men with prostate cancer
Authors: Knuuttila Emma , Riikonen Jarno , Syvälä Heimo , Auriola Seppo , Murtola Teemu J.
Published: June 2019

Background

Statins have anticancer effects on prostate cancer both in vitro and in vivo. It is unclear whether this is due to systemic cholesterol‐lowering or direct local growth inhibition in the prostate. It is also unclear whether statins can access the prostate; lipophilic statins could, in theory, pass lipid‐enriched cell membranes by passive diffusion. However, statin concentrations in the human prostate have not been measured before.

Methods

The study population was based on a randomized clinical trial where 158 men with prostate cancer were randomized to use 80 mg atorvastatin (ATV) or placebo daily for a median of 27 days before radical prostatectomy. ATV and atorvastatin lactone (ATV‐Lactone) concentrations in the plasma and in the prostate were measured with mass spectrometry in men randomized to the ATV arm. Linear trends between intraprostatic concentration and plasma concentration, body mass index, age, and duration of intervention were examined. The relative tissue concentrations of ATV and ATV‐Lactone were calculated in prostatic tissue and plasma to evaluate drug homeostasis. Subgroup analyses were stratified by tumor and population characteristics.

Results

The analysis involved a total of 55 men. When limited to men whose tissue concentrations of ATV was measurable (n = 28, 50%), median ATV concentration was 212% higher in the tissue (median concentration 17.6 ng/g) compared to the plasma (median concentration 3.6 ng/mL). Also, ATV‐L concentration was 590% higher in the tissue as compared to the plasma concentration. No statistically significant linear trends between the plasma and tissue concentrations were observed.

When comparing the relative concentration of atorvastatin lactone over ATV, the concentrations were in balance in the plasma, In the prostate, however, the relative concentration of atorvastatin lactone was 57% lower compared to ATV (P = .009 for the difference between prostate tissue and plasma). No effect modification by tumor or population characteristics was observed.

Conclusions

Measurable ATV concentrations in the prostate support ATV's ability to access the prostate from the circulation. ATV may accumulate in the prostate as intraprostatic concentrations are elevated compared to the plasma concentration.
Amyloidogenicity of naturally occurring full‐length animal IAPP variants
Authors: Palato Larry M. , Pilcher Shannon , Oakes Alissa , Lamba Arleen , Torres Jaris , Ledesma Monjaraz Litza I. , Munoz Crystabel , Njoo Edward , Rinauro Dillon J. , Menefee Kate Alexandra , Tun Angela , Jauregui Betssy L. , Shapiro Sarah , Nossiff Olivia H. , Olivares Eileen , Chang Kevin , Nguyen Viviane , Nogaj Luiza A. , Moffet David A.
Published: June 2019

The aggregation of the 37‐amino acid polypeptide human islet amyloid polypeptide (hIAPP), as either insoluble amyloid or as small oligomers, appears to play a direct role in the death of human pancreatic β‐islet cells in type 2 diabetes. hIAPP is considered to be one of the most amyloidogenic proteins known. The quick aggregation of hIAPP leads to the formation of toxic species, such as oligomers and fibers, that damage mammalian cells (both human and rat pancreatic cells). Whether this toxicity is necessary for the progression of type 2 diabetes or merely a side effect of the disease remains unclear. If hIAPP aggregation into toxic amyloid is on‐path for developing type 2 diabetes in humans, islet amyloid polypeptide (IAPP) aggregation would likely need to play a similar role within other organisms known to develop the disease. In this work, we compared the aggregation potential and cellular toxicity of full‐length IAPP from several diabetic and nondiabetic organisms whose aggregation propensities had not yet been determined for full‐length IAPP.
Temperature‐Dependent Characteristics of AlGaN/GaN Nanowire Channel High Electron Mobility Transistors
Authors: He Yunlong , Huang Zeyang , Zhang Meng , Wu Mei , Mi Minhan , Wang Chong , Yang Ling , Zhang Chunfu , Guo Lixin , Ma Xiaohua , Hao Yue
Published: June 2019

In this work, three AlGaN/GaN nanowire channel high electron mobility transistors (NC‐HEMTs) with different channel widths have been fabricated. The temperature dependent characteristics of NC‐HEMTs are studied and compared with conventional HEMT. The results show that the on‐state current density of NC‐HEMTs have weaker temperature dependence, and the threshold voltage variation of NC‐HEMTs is lower. In addition, the temperature characteristics of the drain‐induced barrier lowering of NC‐HEMT are first reported. Moreover, there are two main scattering mechanisms that influence the transconductance characteristics of NC‐HEMT, phonon scattering and Coulomb scattering, which correspond to different gate voltage biases.