bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of a vibrationally excited level in methyl formate through microwave and far-infrared spectroscopy
Authors: Kobayashi Kaori , Sakai Yusuke , Fujitake Masaharu , Tokaryk Dennis W. , Billinghurst Brant E. , Ohashi Nobukimi
Published: April 2020

Methyl formate (HCOOCH3) is an important interstellar molecule. More than 1000 rotational transitions including those from the ground state, torsionally excited states, and of its isotopologues have been observed towards several astrophysical sources. The laboratory spectra of methyl formate in the microwave spectral region contain many unassigned transitions and many of them are likely to be due to rotational transitions in the low-lying excited states. We report the laboratory identification of new rotational transitions in the COC deformation (ν12) excited state. The identification was made possible by combining the microwave data with rotation–vibration spectra taken in the far-infrared region at the Canadian Light Source synchrotron.
Bifurcations of Negative Responses to Positive Feedback Current Mediated by Memristor in a Neuron Model with Bursting Patterns
Authors: Wu Fuqiang , Gu Huaguang
Published: April 2020

In contrast to traditional viewpoint that positive feedback current always enhances neural firing activities, in the present paper, we identify that the excitatory feedback current mediated by memristor can induce negative responses of bursting patterns, which can be well interpreted with bifurcations. For the Hindmarsh–Rose neuron model without memristor, the period-adding bifurcations of bursting patterns and increase of firing frequency can be induced by increasing the excitatory effect of the background current. After introducing a memristor to simulate the biological synapse or electromagnetic induction effect, inverse period-adding or complex bifurcations of bursting patterns are induced by the excitatory feedback current mediated by the memristor. The number of spikes per burst becomes smaller and the firing frequency becomes lower when increasing the positive feedback gain. Such negative responses of bursting patterns to the positive feedback current are demonstrated in a circuit designed with Digital Signal Processor systems of the MatLab software. Furthermore, the underlying bifurcation mechanism of the negative responses to the positive feedback is acquired with fast–slow variable dissection method. With increasing feedback gain, the initial phase of the burst, which corresponds to a saddle-node bifurcation point of the fast subsystem, delays, while the termination phase of the burst, which corresponds to a saddle-homoclinic bifurcation point, remains unchanged. Therefore, the burst becomes narrower with increasing feedback gain, which leads to decrease in the number of spikes within a burst and decrease in firing frequency. The results present a paradoxical nonlinear phenomenon and the dynamical mechanism, which is helpful for understanding the functions of memristor and roles of the electromagnetic induction current.
An Improved Return Maps Method for Parameter Estimation of Chaotic Systems
Authors: Peng Yuexi , Sun Kehui , He Shaobo
Published: April 2020

Recently, an effective method called return maps is proposed for the parameter estimation of chaotic systems. However, high time-consumption limits practical applications. In this paper, we focus on this problem, and an improved return maps method is proposed. It combines the differential evolution algorithm with the return maps method, and simplifies the calculation process of Euclidean distance. Numerical simulations are carried out on two fractional-order chaotic systems, and the other five methods are used as the comparison. Results show that the improved method can accurately estimate the parameters of chaotic systems, and it saves much time than does the classical return maps method. Furthermore, the proposed method also exhibits good anti-noise performance.
Asymptotic Analysis of an Age-Structured HIV Infection Model with Logistic Target-Cell Growth and Two Infecting Routes
Authors: Yan Dongxue , Fu Xianlong
Published: April 2020

This paper deals with an age-structured HIV infection model with logistic growth for target cells and both virus-to-cell and cell-to-cell infection routes. Based on the existence of the infection-free and infection equilibria and some rigorous analyses for the considered model, we study the asymptotic stability of these equilibria via determining the distribution of eigenvalues. We also address the persistence of the solution semi-flow by proving the existence of a global attractor. Furthermore, Hopf bifurcation occurring at the positive steady state is exploited. At last, some numerical examples are provided to illustrate the obtained results.
An Image Encryption Algorithm Based on Random Walk and Hyperchaotic Systems
Authors: Xu Cong , Sun Jingru , Wang Chunhua
Published: April 2020

In this paper, we propose an image encryption algorithm based on random walk and two hyperchaotic systems. The random walk method is adopted to scramble the position of pixels within a block. Furthermore, the permutation operation between blocks is presented to enhance the scramble effect. Thus, high correlation among pixels of original image is broken by permutation. Moreover, the chosen plaintext attack is used to test the anti-attack ability of the proposed algorithm. By analyzing experimental results and comparing with other image encryption algorithms, we show that the proposed algorithm has better performance and higher security.
The Entropy and Reversibility of Cellular Automata on Cayley Tree
Authors: Akın Hasan , Chang Chih-Hung
Published: April 2020

In this paper, we study linear cellular automata (CAs) on Cayley tree of order [Formula: see text] over the field [Formula: see text] (the set of prime numbers modulo [Formula: see text]). After revealing the rule matrix corresponding to cellular automata on Cayley tree with the null boundary condition, we analyze the reversibility problem of these cellular automata for some given values of [Formula: see text] and the levels [Formula: see text] of Cayley tree. The necessary and sufficient conditions for determining whether a CA is reversible or not are demonstrated. Furthermore, we compute the measure-theoretical entropy of the cellular automata which we define on Cayley tree. We show that for CAs on Cayley tree, the measure entropy with respect to uniform Bernoulli measure is infinity.
Engro Fertilizers Limited: Cost of Capital and Valuation
Authors: Seyyed Fazal Jawad , Ashfaq Hafsa
Published: April 2020

The case is based on Engro Fertilizers Limited (EFERT), a company listed on the Pakistan Stock Exchange and an important player in the fertilizer sector of Pakistan. The case describes the role of a senior equity analyst at Intermarket Securities Limited (IMS), Qasim Ahmad, who is preparing the Intermarket Pulse report on Pakistan’s fertilizer sector. The upcoming report, due on 16 February 2017, requires a comprehensive analysis. Qasim gathered the background information on the fertilizer sector in Pakistan as well as EFERT and asked a newly hired junior analyst to prepare an estimate of EFERT’s cost of capital. Now Qasim has to review the workings of the new hire and then prepare the cash flow forecast to determine the stock’s target price.
Feature Suites Company Limited: The Management Contract of Manor Inn
Authors: Racela Olimpia C. , Narula Ravisara
Published: April 2020

Feature Suites Co. Ltd. (Feature Suites), a hospitality and restaurant business, had hired Agate Hospitality Group (Agate) in 1987 to manage the operations of its Manor Inn under Agate’s Modish hotel brand. The management contract between Feature Suites and Agate would end on 31 January 2018 and the ongoing 10 months of negotiations for contract renewal needed to come to a close. The two parties had different views on the level of the operator guarantees in return of the proposed maintenance budget of THB250 million. Feature Suites needed to decide whether to renew the existing contract or to pursue another alternative to manage its Manor Inn hotel operations.
Fault geometry, segmentation and slip distribution associated with the 1939 Erzincan earthquake rupture along the North Anatolian fault, Turkey
Authors: Emre Ömer , Kondo Hisao , Özalp Selim , Elmacı Hasan
Published: April 2020

The intracontinental plate boundary, dextral North Anatolian fault (NAF), is well-known by the westward migration of the multi-segment large earthquake sequence during the twentieth century. The sequence, started by the 1939 Erzincan earthquake (M
w
7.9), resulted in a 330 km-long multi-segment surface rupture. Slip magnitudes are relatively consistent on each segment, with averages per segment slip varying from 2.3 to 8.8 m, with maximum horizontal displacements up to 10.5 m. The variable slip along the 1939 surface rupture may be attributed to the differences in the strain accumulated on each segment between the penultimate event and the 1939 event, with higher slip measured in segments with greater elapse times. Deviation of the west end of the rupture propagation from the main strand of the NAF to the Ezinepazarı fault splay appears to be controlled not only by accumulated strain on that fault splay, but also by factors such as rupture direction, fault geometry and the level of stress transferred at the segment boundary. Analysis of rupture geometry and slip distribution in the 1939 earthquake has implications for source-fault characterization of similar multi-segment strike-slip faults.
Anode Corrosion of Zn-Air Fuel Cell: Mechanism and Protection
Authors: Huang Shangwei , Pei Pucheng , Wang Zhezheng
Published: April 2020

Zn-air fuel cells are potential for grid-scale storage and portable power sources, which combine high energy density and low cost. However, Zn anodes undergo the corrosion in both the operation and downtime. The corrosion of the Zn electrode causes the low utilization of active materials, the release of hydrogen and heat. The temperature of the Zn electrode even rises above 100 °C in downtime. Here we show that replacing the electrolyte with tiny amounts of glycerol can avoid the thermal runaway of the Zn electrode in downtime. We demonstrate the mechanism of Zn electrode corrosion in the aqueous electrolytes under all operating conditions. Under the open-circuit conditions, the electrode potential causes corrosion. At operation condition, the combination of electrode potential and abscission of Zn particles leads to the corrosion, and the dynamic change of solution/electrode interface brings inductance characteristics. These conclusions and strategies can be applied to not only Zn-air fuel cells but also other metal-based electrodes in aqueous electrolytes.
TRPV1 activation stimulates NKCC1 and increases hydrostatic pressure in the mouse lens
Authors: Shahidullah Mohammad , Mandal Amritlal , Mathias Richard T. , Gao Junyuan , Križaj David , Redmon Sarah , Delamere Nicholas A.
Published: April 2020

The porcine lens response to a hyperosmotic stimulus involves an increase in the activity of an ion cotransporter sodium-potassium/two-chloride cotransporter 1 (NKCC1). Recent studies with agonists and antagonists pointed to a mechanism that appears to depend on activation of transient receptor potential vanilloid 1 (TRPV1) ion channels. Here, we compare responses in lenses and cultured lens epithelium obtained from TRPV1−/− and wild type (WT) mice. Hydrostatic pressure (HP) in lens surface cells was determined using a manometer-coupled microelectrode approach. The TRPV1 agonist capsaicin (100 nM) caused a transient HP increase in WT lenses that peaked after ∼30 min and then returned toward baseline. Capsaicin did not cause a detectable change of HP in TRPV1−/− lenses. The NKCC inhibitor bumetanide prevented the HP response to capsaicin in WT lenses. Potassium transport was examined by measuring Rb+ uptake. Capsaicin increased Rb+ uptake in cultured WT lens epithelial cells but not in TRPV1−/− cells. Bumetanide, A889425, and the Akt inhibitor Akti prevented the Rb+ uptake response to capsaicin. The bumetanide-sensitive (NKCC-dependent) component of Rb+ uptake more than doubled in response to capsaicin. Capsaicin also elicited rapid (<2 min) NKCC1 phosphorylation in WT but not TRPV1−/− cells. HP recovery was shown to be absent in TRPV1−/− lenses exposed to hyperosmotic solution. Bumetanide and Akti prevented HP recovery in WT lenses exposed to hyperosmotic solution. Taken together, responses to capsaicin and hyperosmotic solution point to a functional role for TRPV1 channels in mouse lens. Lack of NKCC1 phosphorylation and Rb+ uptake responses in TRPV1−/− mouse epithelium reinforces the notion that a hyperosmotic challenge causes TRPV1-dependent NKCC1 activation. The results are consistent with a role for the TRPV1-activated signaling pathway leading to NKCC1 stimulation in lens osmotic homeostasis.
Isoform-specific Na,K-ATPase and membrane cholesterol remodeling in motor endplates in distinct mouse models of myodystrophy
Authors: Kravtsova Violetta V. , Bouzinova Elena V. , Chibalin Alexander V. , Matchkov Vladimir V. , Krivoi Igor I.
Published: April 2020

Na,K-ATPase is a membrane transporter that is critically important for skeletal muscle function. Mdx and Bla/J mice are the experimental models of Duchenne muscular dystrophy and dysferlinopathy that are known to differ in the molecular mechanism of the pathology. This study examines the function of α1- and α2-Na,K-ATPase isozymes in respiratory diaphragm and postural soleus muscles from mdx and Bla/J mice compared with control С57Bl/6 mice. In diaphragm muscles, the motor endplate structure was severely disturbed (manifested by defragmentation) in mdx mice only. The endplate membrane of both Bla/J and mdx mice was depolarized due to specific loss of the α2-Na,K-ATPase electrogenic activity and its decreased membrane abundance. Total FXYD1 subunit (modulates Na,K-ATPase activity) abundance was decreased in both mouse models. However, the α2-Na,K-ATPase protein content as well as mRNA expression were specifically and significantly reduced only in mdx mice. The endplate membrane cholesterol redistribution was most pronounced in mdx mice. Soleus muscles from Bla/J and mdx mice demonstrated reduction of the α2-Na,K-ATPase membrane abundance and mRNA expression similar to the diaphragm muscles. In contrast to diaphragm, the α2-Na,K-ATPase protein content was altered in both Bla/J and mdx mice; membrane cholesterol re-distribution was not observed. Thus, the α2-Na,K-ATPase is altered in both Bla/J and mdx mouse models of chronic muscle pathology. However, despite some similarities, the α2-Na,K-ATPase and cholesterol abnormalities are more pronounced in mdx mice.
Aurothioglucose enhances proangiogenic pathway activation in lungs from room air and hyperoxia-exposed newborn mice
Authors: Dunigan-Russell Katelyn , Lin Vivian , Silverberg Mary , Wall Stephanie B. , Li Rui , Gotham John , Nicola Teodora , Sridharan Anusha , Snowball John , Delaney Cassidy , Li Qian , Tipple Trent E.
Published: April 2020

Bronchopulmonary dysplasia (BPD), a long-term respiratory morbidity of prematurity, is characterized by attenuated alveolar and vascular development. Supplemental oxygen and immature antioxidant defenses contribute to BPD development. Our group identified thioredoxin reductase-1 (TXNRD1) as a therapeutic target to prevent BPD. The present studies evaluated the impact of the TXNRD1 inhibitor aurothioglucose (ATG) on pulmonary responses and gene expression in newborn C57BL/6 pups treated with saline or ATG (25 mg/kg ip) within 12 h of birth and exposed to room air (21% O2) or hyperoxia (>95% O2) for 72 h. Purified RNA from lung tissues was sequenced, and differential expression was evaluated. Hyperoxic exposure altered ~2,000 genes, including pathways involved in glutathione metabolism, intrinsic apoptosis signaling, and cell cycle regulation. The isolated effect of ATG treatment was limited primarily to genes that regulate angiogenesis and vascularization. In separate studies, pups were treated as described above and returned to room air until 14 days. Vascular density analyses were performed, and ANOVA indicated an independent effect of hyperoxia on vascular density and alveolar architecture at 14 days. Consistent with RNA-seq analyses, ATG significantly increased vascular density in room air, but not in hyperoxia-exposed pups. These findings provide insights into the mechanisms by which TXNRD1 inhibitors may enhance lung development.
High-intensity, low-frequency repetitive transcranial magnetic stimulation enhances excitability of the human corticospinal pathway
Authors: D’Amico Jessica M. , Dongés Siobhan C. , Taylor Janet L.
Published: April 2020

In this study, we present a novel, intensity-dependent repetitive transcranial magnetic stimulation (rTMS) protocol that induces lasting, plastic changes within the corticospinal tract. High-intensity rTMS at a frequency of 0.1 Hz induces facilitation of motor evoked potentials (MEPs) lasting at least 35 min. Additionally, these changes are not limited only to small MEPs but occur throughout the recruitment curve. Finally, facilitation of MEPs following high-intensity rTMS does not appear to be due to changes in intracortical inhibition or facilitation.
The Na+-K+-ATPase is needed in glia of touch receptors for responses to touch inC. elegans
Authors: Johnson Christina K. , Fernandez-Abascal Jesus , Wang Ying , Wang Lei , Bianchi Laura
Published: April 2020

Increasing evidences support that accessory cells in mechanosensors regulate neuronal output; however, the glial molecular mechanisms that control this regulation are not fully understood. We show here in Caenorhabditis elegans that specific glial Na+-K+-ATPase genes are needed for nose touch-avoidance behavior. Our data support the requirement of these Na+-K+-ATPases for homeostasis of Na+and K+in nose touch receptors. Our data add to our understanding of glial regulation of mechanosensors.
Titin: A Tunable Spring in Active Muscle
Authors: Nishikawa Kiisa
Published: April 2020

Muscle has conventionally been viewed as a motor that converts chemical to kinetic energy in series with a passive spring, but new insights emerge when muscle is viewed as a composite material whose elastic elements are tuned by activation. New evidence demonstrates that calcium-dependent binding of N2A titin to actin increases titin stiffness in active skeletal muscles, which explains many long-standing enigmas of muscle physiology.
Numerical Solution of Fractional-Order HIV Model Using Homotopy Method
Authors: Aljhani Sami , Md Noorani Mohd Salmi , Alomari A. K.
Published: April 2020

In this study, we construct a convergent algorithm for generating an approximate analytic solution for the fractional HIV infection of CD4+ T cells with Atangana–Baleanu fractional derivatives in the Caputo sense. We compute the solution by utilizing the fractional homotopy analysis transform method (FHATM) and achieved a convergence region of the solution by employing an auxiliary parameter. Moreover, we apply a numerical scheme proposed by Toufik and Atangana for solving this kind of problem and compared with our results. A good agreement between the new algorithm and the numerical scheme is remarkable. The solution via the present algorithm can be obtained without any linearization or discretization which makes it reliable and easy to apply.
Fernblock® Upregulates NRF2 Antioxidant Pathway and Protects Keratinocytes from PM2.5-Induced Xenotoxic Stress
Authors: Delgado-Wicke Pablo , Rodríguez-Luna Azahara , Ikeyama Yoshifumi , Honma Yoichi , Kume Toshiaki , Gutierrez María , Lorrio Silvia , Juarranz Ángeles , González Salvador
Published: April 2020

Humans in modern industrial and postindustrial societies face sustained challenges from environmental pollutants, which can trigger tissue damage from xenotoxic stress through different mechanisms. Thus, the identification and characterization of compounds capable of conferring antioxidant effects and protection against these xenotoxins are warranted. Here, we report that the natural extract of Polypodium leucotomos named Fernblock®, known to reduce aging and oxidative stress induced by solar radiations, upregulates the NRF2 transcription factor and its downstream antioxidant targets, and this correlates with its ability to reduce inflammation, melanogenesis, and general cell damage in cultured keratinocytes upon exposure to an experimental model of fine pollutant particles (PM2.5). Our results provide evidence for a specific molecular mechanism underpinning the protective activity of Fernblock® against environmental pollutants and potentially other sources of oxidative stress and damage-induced aging.
Topological Indices of Certain Transformed Chemical Structures
Authors: Zuo Xuewu , Liu Jia-Bao , Iqbal Hifza , Ali Kashif , Rizvi Syed Tahir Raza
Published: April 2020

Topological indices like generalized Randić index, augmented Zagreb index, geometric arithmetic index, harmonic index, product connectivity index, general sum-connectivity index, and atom-bond connectivity index are employed to calculate the bioactivity of chemicals. In this paper, we define these indices for the line graph of k-subdivided linear [n] Tetracene, fullerene networks, tetracenic nanotori, and carbon nanotube networks.
Intravitreal Injections in Arc Sterile Setting: Safety Profile after More Than 10,000 Treatments
Authors: Furino Claudio , Grassi Maria Oliva , Bini Vito , Nacucchi Annalisa , Boscia Francesco , Reibaldi Michele , Recchimurzo Nicola , Alessio Giovanni
Published: April 2020

Purpose. To report the occurrence of endophthalmitis and other complications after intravitreal injections (IVIs) in the Arc Sterile setting. Methods. A retrospective study that enrolled all patients who underwent IVIs between November 2017 and March 2019, collecting data about the patient’s gender and age, type of injected drug, diagnosis, other ocular pathologies, physician and possible occurrence of endophthalmitis, or other complications. Results. Ten thousand and eighty-three IVIs were performed during the study period, involving 2014 eyes of 1,670 patients with an average age of 71.37 ± 11.63 years. The injected drugs included ranibizumab (54.6%), aflibercept (38.0%), dexamethasone (6.7%), pegaptanib (0.3%), bevacizumab (0.4%), and ocriplasmin (0.01%). The diagnosis included neovascular age-related macular degeneration (859), myopic choroidal neovascularization (154), diabetic macular edema (576), retinal vein occlusion (203), and miscellaneus diagnosis (222). No cases of endophthalmitis were recorded. One hundred and sixty-nine cases of ocular hypertension were detected, while the most frequent complication was subconjunctival hemorrhage, identified after 1,180 IVIs. The residents performed over 80% of IVIs, but there was no statistically significant difference in incidence of complications between the residents group and consultants group. Conclusions. Arc Sterile seems to be a safe setting in which IVIs can be carried out, regarding infective risk, and it is easy to set up compared to operation theatre and useful to improve intravitreal injections governance.
Inhibition of GPR91 Reduces Inflammatory Mediators Involved in Active Labor in Myometrium
Authors: Lim Ratana , Lappas Martha
Published: April 2020

Problem. Some G-protein-coupled receptors (GPCRs) are regulators of inflammation, yet the role of the GPRC, GPR91, is unknown in human myometrium during the processes of human labor and delivery, a major inflammatory event. Method of Study. GPR91 mRNA expression was assessed using RT-qPCR in myometrium obtained from women at term Caesarean section in the absence of labor and during active spontaneous labor and in a mouse model of inflammation-induced preterm labor. Human primary myometrial cells were used to determine the effect of proinflammatory mediators on GPR91 and the effect of GPR91 siRNA on prolabor mediators. Statistical significance was ascribed to a P<0.05. Results. GPR91 mRNA expression was significantly higher in myometrium from women during term spontaneous labor compared to no labor. Likewise, in mice, GPR91 mRNA expression was significantly upregulated in myometrium during inflammation-induced preterm labor compared to preterm no labor. In myometrial cells, IL1B and TNF significantly increased GPR91 mRNA expression. Knockdown of GPR91 by siRNA in myometrial cells significantly suppressed the secretion and/or expression of IL1B- and TNF-induced proinflammatory cytokines (GM-CSF, IL1A, IL1B, and IL6) and chemokines (CXCL8 and CCL2), myometrial contractility (expression of the contraction-associated proteins PTGFR and CX43, secretion of the uterotonic PGF2α, and in situ collagen gel contraction), and the transcription factor NF-κB. Conclusion. Our findings demonstrate that GPR91 is involved in the genesis of proinflammatory and prolabor mediators induced by IL1B or TNF and collectively suggest that GPR91 may contribute to augmentation of the labor processes.
Assessment of Lumbar Lordosis Distribution with a Novel Mathematical Approach and Its Adaptation for Lumbar Intervertebral Disc Degeneration
Authors: Sandor Zoltan , Rathonyi Gabor Kristof , Dinya Elek
Published: April 2020

Introduction. Low back pain and disc degeneration could be linked to global spinal geometry. Our study aimed to develop a reliable new mathematical method to assess the local distribution of total lumbar lordosis with a single numeric parameter and compare it with lumbar intervertebral disc degeneration using routine MRI scans. Methods. An online, open access, easy-to-use platform for measurements was developed based on a novel mathematical approach using MRIs of 60 patients. Our Spinalyze Software can be used online with uploaded MRIs. Several new parameters were introduced and assessed to describe variation in segmental lordosis distribution with a single numerical value. The Pfirrmann grading system was used for the classification of lumbar intervertebral disc degeneration. Relationships were investigated between the grade categories of L1-S1 lumbar discs and the MRI morphological parameters with correlation analysis. Results. Results confirm that the determination of measurement points and calculated parameters are reliable (ICCs and Pearson r values > 0.90), and these parameters were independent of gender. The digression percentage (K%), one of our new parameters, did not show a statistical relationship with the Cobb-angle. According to our results, the maximum deflection breaking-point of lumbar lordosis and its location can be different with the same Cobb-angle and the distribution of global lordosis is uneven because the shape of the lumbar lordosis is shifted downward and centered around the L4 lumbar vertebra. The interobserver reliability of the Pfirrmann grades reading was in the excellent agreement category (88.33% agreement percentage, 0.84 kappa), and digression percentage (K%) showed a significant negative correlation with all L1-S1 disc grades with increasing r correlation values. This means that the smaller the value of digression percentage (K%), the more the number of worn discs in the lower lumbar sections. Conclusions. Spinalyze Software based on a novel mathematical approach provides a free, easy-to-use, reliable, and online measurement tool using standard MRIs to approximate the curvature of lumbar lordosis. The new reliable K% (digression percentage) is one single quantitative parameter to assess the local distribution of total lumbar lordosis. The results indicate that digression percentage (K%) may possibly be associated with the development of lumbar intervertebral disc degeneration. Further evaluation is needed to assess its behavior and advantage.
Sodium Butyrate Protects N2a Cells against Aβ Toxicity In Vitro
Authors: Sun Jingxuan , Yuan Boyu , Wu Yancheng , Gong Yuhong , Guo Wenjin , Fu Shoupeng , Luan Yongxin , Wang Wei
Published: April 2020

Alzheimer’s disease (AD) is a common neurodegenerative disease. Aβ plays an important role in the pathogenesis of AD. Sodium butyrate (NaB) is a short-chain fatty acid salt that exerts neuroprotective effects such as anti-inflammatory, antioxidant, antiapoptotic, and cognitive improvement in central nervous system diseases. The aim of this study is to research the protective effects of NaB on neurons against Aβ toxicity and to uncover the underlying mechanisms. The results showed that 2 mM NaB had a significant improvement effect on Aβ-induced N2a cell injury, by increasing cell viability and reducing ROS to reduce injury. In addition, by acting on the GPR109A receptor, NaB regulates the expression of AD-related genes such as APP, NEP, and BDNF. Therefore, NaB protects N2a cells from Aβ-induced cell damage through activating GPR109A, which provides an innovative idea for the treatment of AD.
Cardiomyocyte Contractility and Autophagy in a Premature Senescence Model of Cardiac Aging
Authors: Häseli Steffen , Deubel Stefanie , Jung Tobias , Grune Tilman , Ott Christiane
Published: April 2020

Globally, cardiovascular diseases are the leading cause of death in the aging population. While the clinical pathology of the aging heart is thoroughly characterized, underlying molecular mechanisms are still insufficiently clarified. The aim of the present study was to establish an in vitro model system of cardiomyocyte premature senescence, culturing heart muscle cells derived from neonatal C57Bl/6J mice for 21 days. Premature senescence of neonatal cardiac myocytes was induced by prolonged culture time in an oxygen-rich postnatal environment. Age-related changes in cellular function were determined by senescence-associated β-galactosidase activity, increasing presence of cell cycle regulators, such as p16, p53, and p21, accumulation of protein aggregates, and restricted proteolysis in terms of decreasing (macro-)autophagy. Furthermore, the culture system was functionally characterized for alterations in cell morphology and contractility. An increase in cellular size associated with induced expression of atrial natriuretic peptides demonstrated a stress-induced hypertrophic phenotype in neonatal cardiomyocytes. Using the recently developed analytical software tool Myocyter, we were able to show a spatiotemporal constraint in spontaneous contraction behavior during cultivation. Within the present study, the 21-day culture of neonatal cardiomyocytes was defined as a functional model system of premature cardiac senescence to study age-related changes in cardiomyocyte contractility and autophagy.
Identification of a Novel Eight‐lncRNA Prognostic Signature for HBV‐HCC and Analysis of Their Functions Based on Coexpression and ceRNA Networks
Authors: Zhao Xiaonan , Bai Zhenzi , Li Chenghua , Sheng Chuanlun , Li Hongyan
Published: April 2020

Studies have demonstrated the prognosis potential of long noncoding RNAs (lncRNAs) for hepatocellular carcinoma (HCC), but specific lncRNAs for hepatitis B virus‐ (HBV‐) related HCC have rarely been reported. This study was aimed at identifying a lncRNA prognostic signature for HBV‐HCC and exploring their underlying functions. The sequencing dataset was collected from The Cancer Genome Atlas database as the training set, while the microarray dataset was obtained from the European Bioinformatics Institute database (E‐TABM‐36) as the validation set. Univariate and multivariate Cox regression analyses identified that eight lncRNAs (TSPEAR‐AS1, LINC00511, LINC01136, MKLN1‐AS, LINC00506, KRTAP5‐AS1, ZNF252P‐AS1, and THUMPD3‐AS1) were significantly associated with overall survival (OS). These eight lncRNAs were used to construct a risk score model. The Kaplan‐Meier survival curve results showed that this risk score can significantly differentiate the OS between the high‐risk group and the low‐risk group. Receiver operating characteristic curve analysis demonstrated that this risk score exhibited good prediction effectiveness (area under the curve (AUC) = 0.990 for the training set; AUC = 0.903 for the validation set). Furthermore, this lncRNA risk score was identified as an independent prognostic factor in the multivariate analysis after adjusting other clinical characteristics. The crucial coexpression (LINC00511‐CABYR, THUMPD3‐AS1‐TRIP13, LINC01136‐SFN, LINC00506‐ANLN, and KRTAP5‐AS1/TSPEAR‐AS1/MKLN1‐AS/ZNF252P‐AS1‐MC1R) or competing endogenous RNA (THUMPD3‐AS1‐hsa‐miR‐450a‐TRIP13) interaction axes were identified to reveal the possible functions of lncRNAs. These genes were enriched into cell cycle‐related biological processes or pathways. In conclusion, our study identified a novel eight‐lncRNA prognosis signature for HBV‐HCC patients and these lncRNAs may be potential therapeutic targets.
Diagnostic Accuracy of Quantitative Micro-Elastography for Margin Assessment in Breast-Conserving Surgery
Authors: Kennedy Kelsey M. , Zilkens Renate , Allen Wes M. , Foo Ken Y. , Fang Qi , Chin Lixin , Sanderson Rowan W. , Anstie James , Wijesinghe Philip , Curatolo Andrea , Tan Hsern Ern I. , Morin Narelle , Kunjuraman Bindu , Yeomans Chris , Chin Synn Lynn , DeJong Helen , Giles Katharine , Dessauvagie Benjamin F. , Latham Bruce , Saunders Christobel M. , Kennedy Brendan F.
Published: April 2020

Inadequate margins in breast-conserving surgery (BCS) are associated with an increased likelihood of local recurrence of breast cancer. Currently, approximately 20% of BCS patients require repeat surgery due to inadequate margins at the initial operation. Implementation of an accurate, intraoperative margin assessment tool may reduce this re-excision rate. This study determined, for the first time, the diagnostic accuracy of quantitative micro-elastography (QME), an optical coherence tomography (OCT)–based elastography technique that produces images of tissue microscale elasticity, for detecting tumor within 1 mm of the margins of BCS specimens. Simultaneous OCT and QME were performed on the margins of intact, freshly excised specimens from 83 patients undergoing BCS and on dissected specimens from 7 patients undergoing mastectomy. The resulting three-dimensional images (45 × 45 × 1 mm) were coregistered with postoperative histology to determine tissue types present in each scan. Data from 12 BCS patients and the 7 mastectomy patients served to build a set of images for reader training. One hundred and fifty-four subimages (10 × 10 × 1 mm) from the remaining 71 BCS patients were included in a blinded reader study, which resulted in 69.0% sensitivity and 79.0% specificity using OCT images, versus 92.9% sensitivity and 96.4% specificity using elasticity images. The quantitative nature of QME also facilitated development of an automated reader, which resulted in 100.0% sensitivity and 97.7% specificity. These results demonstrate high accuracy of QME for detecting tumor within 1 mm of the margin and the potential for this technique to improve outcomes in BCS.

Significance:

An optical imaging technology probes breast tissue elasticity to provide accurate assessment of tumor margin involvement in breast-conserving surgery.
Regression of Papillary Thyroid Cancer during Nivolumab for Renal Cell Cancer
Authors: Palermo Andrea , Napolitano Andrea , Maggi Daria , Naciu Anda Mihaela , Tabacco Gaia , Manfrini Silvia , Crescenzi Anna , Taffon Chiara , Pantano Francesco , Vincenzi Bruno , Tonini Guiseppe , Santini Daniele
Published: April 2020

Immune checkpoint inhibitors have been recently approved for cancer treatment. Nivolumab is a monoclonal antibody specific for programmed cell death-1 (PD-1) that modulates T-cell response. It was initially used for the treatment of malignant melanoma and then approved in other cancers, such as non-small cell lung cancer and clear cell renal cell carcinoma (ccRCC). So far, the activity of nivolumab in patients with thyroid malignancies has been reported in a single case of anaplastic thyroid cancer. Here, we report the case of a patient with ccRCC who developed a papillary thyroid carcinoma (PTC) under first-line sunitinib treatment. During nivolumab, the second-line treatment for ccRCC, we unexpectedly observed a complete regression of PTC.
Serum Klotho, Cardiovascular Events, and Mortality in Nondiabetic Chronic Kidney Disease
Authors: Yang Ke , Yang Jiangxin , Bi Xianjin , Yu Zhikai , Xiao Tangli , Huang Yinghui , Liu Yong , Xiong Jiachuan , Zhao Jinghong
Published: April 2020

Background: Experimental studies indicate that Klotho deficiency is a pathogenic factor for CKD-related complications, including cardiovascular disease (CVD). However, the association between serum Klotho and clinical outcomes in nondiabetic CKD patients needs to be further clarified. We aimed to determine whether serum Klotho levels are associated with CVD events and mortality in predialysis CKD patients without diabetes. Methods: A total of 336 CKD stage 2–5 predialysis patients without diabetes were recruited and followed from the end of 2014 to January 2019 for CVD events and overall mortality. Serum Klotho was detected by ELISA and divided into quartiles (lowest, middle, second highest, and highest quartiles) according to their serum Klotho category. Results: After a median follow-up of 3.52 years (IQR 3.34–3.76), Kaplan-Meier analysis showed that, compared to participants with a Klotho level in the highest quartile (the reference category), those in the lowest Klotho quartile were associated with a higher all-cause mortality risk (HR = 7.05; 95% CI 1.59–31.25) and a higher CVD event risk (HR = 3.02; 95% CI 1.45–6.30). In addition, the middle Klotho quartile was also associated with CVD event risk (HR = 2.56; 95% CI 1.21–5.41). Moreover, in the multivariate-adjusted model, the lowest Klotho quartile remained significantly associated with all-cause mortality (HR = 5.17; 95% CI 1.07–24.96), and the middle Klotho quartile maintained a significant association with CVD event risk (HR = 2.32; 95% CI 1.03–5.21). Conclusion: These results suggest that lower serum Klotho levels are independently associated with overall mortality and CVD events in nondiabetic predialysis CKD patients.
Fibrolamellar Carcinoma: A Multimodal Approach
Authors: Barreira João Vasco , Silva Nádia , Parmanande Anuraj , Rocha Manuel , Coelho João S. , Marques Hugo Pinto , da Luz Ricardo
Published: April 2020

Fibrolamellar carcinoma is a rare variant of hepatocellular carcinoma not associated with cirrhosis or viral hepatitis. Serum alpha-fetoprotein levels are usually normal; the histology is of a well-differentiated tumor, and the staging is the same as for hepatocellular carcinoma. We describe the case of a female patient in her 4th decade of life with a diagnosis of fibrolamellar hepatocellular carcinoma with a multimodal approach. The rare incidence of this cancer and its unusual clinical presentation justifies reporting this case and highlights the importance of multidisciplinary teams in the treatment of cancer patients.
Increased Myocardial Oxygen Consumption Precedes Contractile Dysfunction in Hypertrophic Cardiomyopathy Caused by Pathogenic
TNNT2
Gene Variants
Authors: Parbhudayal Rahana Y. , Harms Hendrik J. , Michels Michelle , van Rossum Albert C. , Germans Tjeerd , van der Velden Jolanda
Published: April 2020

Background

Hypertrophic cardiomyopathy is caused by pathogenic sarcomere gene variants. Individuals with a thin‐filament variant present with milder hypertrophy than carriers of thick‐filament variants, although prognosis is poorer. Herein, we defined if decreased energetic status of the heart is an early pathomechanism in

TNNT
2

(troponin T gene) variant carriers.

Methods and Results

Fourteen individuals with

TNNT
2

variants (genotype positive), without left ventricular hypertrophy (G+/
LVH
−; n=6) and with
LVH
(G+/
LVH
+; n=8) and 14 healthy controls were included. All participants underwent cardiac magnetic resonance and [
11
C]‐acetate positron emission tomography imaging to assess
LV
myocardial oxygen consumption, contractile parameters and myocardial external efficiency. Cardiac efficiency was significantly reduced compared with controls in G+/
LVH
− and G+/
LVH
+. Lower myocardial external efficiency in G+/
LVH
− is explained by higher global and regional oxygen consumption compared with controls without changes in contractile parameters. Reduced myocardial external efficiency in G+/
LVH
+ is explained by the increase in
LV
mass and higher oxygen consumption. Septal oxygen consumption was significantly lower in G+/
LVH
+ compared with G+/
LVH
−. Although
LV
ejection fraction was higher in G+/
LVH
+, both systolic and diastolic strain parameters were lower compared with controls, which was most evident in the hypertrophied septal wall.

Conclusions

Using cardiac magnetic resonance and [
11
C]‐acetate positron emission tomography imaging, we show that G+/
LVH
− have an initial increase in oxygen consumption preceding contractile dysfunction and cardiac hypertrophy, followed by a decline in oxygen consumption in G+/
LVH
+. This suggests that high oxygen consumption and reduced myocardial external efficiency characterize the early gene variant–mediated disease mechanisms that may be used for early diagnosis and development of preventive treatments.
Examining the Suitability of the International Minority Rights Regime as an Avenue for Advancing Self-Determination Claims
Authors: Carvosso Rhys
Published: April 2020

The international legal right of all ‘peoples’ to self-determination applies indeterminately to minority groups. The limited jurisprudence tends toward an ‘internal’ dimension of the right being available to minorities, to be exercised and negotiated domestically. However, where a state-minority negotiation process fails, the international law of self-determination is inadequate to resolve the ensuing deadlock. Accordingly, this article examines the suitability of minority protections under international human rights law (‘minority rights’) as a supplementary set of rules by which disputes concerning the self-determination of minorities might be resolved. It argues that owing to the strong conceptual and doctrinal overlap between the two areas, the enforcement of minority rights is a suitable strategy for advancing a self-determination claim. However, two bars within existing international human rights enforcement procedures – the non-justiciability of self-determination, and the requirement that complainants must be “victims of a violation” – substantially reduce the utility of this strategy at present.
Rwanda Revisited: unamir ii
Authors: Frewen Lieutenant-General J.J.
Published: April 2020

In his article, John Frewen provides a first-hand account of his experience as the Australian contingent operations officer in Rwanda. In so doing he provides insight into the challenges that he and his fellow contingent members faced as they tried to conduct operations in a UN mission that was characterized as having a confused mandate, uncertain use of force authorizations, inadequate resourcing, and plagued by misjudgments as to the intentions of the main actors. A (and, indeed, the degree of respect they would afford the UN), failure of collective will, and misconceptions as to role, all played a part in unamir and unamir ii trying – often heroically – to act as ‘representatives of peace, where no true peace had yet settled
Do Not Intervene: unamir’s Rules of Engagement from the Inside
Authors: Drew Phillip , Beardsley Major (ret’d) Brent
Published: April 2020

This article provides a first-hand account on how the rules of engagement (roe) for the United Nations Assistance Mission in Rwanda (unamir) were developed and implemented. It provides insight into the difficulties that were encountered in developing the roe and getting them authorized. While the mission is often criticized for its failure to protect civilians from genocidal violence, the paper explores the factors that influenced the creation of the rules, and why, given its force structure, unamir was incapable of preventing or stopping the violence.
Wilfully Blind: the Security Council’s Response to Genocide in Rwanda
Authors: Paige Tamsin Phillipa
Published: April 2020

The UN Security Council’s response to the Rwanda genocide was a significant moment in history. It changed the face of international law, cementing individual criminal responsibility for atrocities in the canon of international law. It also saw the Security Council respond to mass atrocities without the consent of the state in question in a manner that ran counter to historical practice. But all of these outcomes are haunted by the fact that decisions made by the Security Council in the build up to the genocide served to create the conditions on the ground that allowed genocide to flourish. This intervention conducts a critical discourse analysis of the statements made by the Permanent Five members of the Security Council justifying these decisions in the context of whether Rwanda constituted a ‘threat to the peace’ under article 39 of the UN Charter, concluding that Security Council through its decisions was complicit in the genocide.
Humanitarian Intervention and R2P
Authors: Henderson Stacey
Published: April 2020

In this piece, Henderson looks to the shadow of Rwanda in terms of the concept of humanitarian intervention, and the evolution of the R2P doctrine. Tracing the re-examination of the conceptualisations of sovereignty and the principle of non-intervention that evolved after Rwanda, Henderson assesses the legal, normative, and institutional challenges that still attend the attainment of its goals. Henderson concludes on a note of cautious optimism: Although it is in no way a panacea, R2P – at the very least – raises the possibility that a greater range of measures may be taken in response to the commission, or anticipation of, atrocity crimes in the future. The legacy of Rwanda is the hope, reflected in R2P, that silence and idleness will never again be the international community’s response to genocide.
Assessing the EU Framework Regulation for the Screening of Foreign Direct Investment—What Is the Effect on Chinese Investors?
Authors: Gadocha Paweł Mateusz
Published: April 2020

An increase of Chinese investment into the territory of the European Union has raised EU regulators’ concerns regarding the public security of the EU. As a result, the new Framework Regulation 2019/452 establishing a framework for the screening of FDI into the EU was adopted as a legal instrument aimed at their control, applicable from 11 October 2020. Adopted within the scope of Common Commercial Policy of the EU, the Framework Regulation, however, might not become an effective legal measure, as its application by Member States both in light of the freedom of movement of capital and the relevant CJEU jurisprudence raises significant legal questions. This article broadly discusses the newly introduced cooperation mechanism between Member States and the European Commission, as well as the relevant effect of the Framework Regulation upon Chinese investment and the pending negotiations of the EU-China BIT.
A synopsis of Lasianthus (Lasiantheae, Rubiaceae) in Thailand and two additional new species

Authors: NAPIROON TIWTAWAT , CHAYAMARIT KONGKANDA , DAWSON SALLY , TILL WALTER , BALSLEV HENRIK
Published: April 2020

The genus Lasianthus in Thailand was studied on the basis of herbarium specimens and field investigation in Thai natural forests and protected areas during 2016–2018. A total of 68 species, including two subspecies and two varieties, are recognized, and their synonymy, distribution, and ecology are provided. Two new species, Lasianthus puffii and L. sithammaratensis are here described as new to science based on morphological characters of fertile and vegetative organs. Lasianthus puffii is similar to L. cyanocarpus but differs from that species by being densely hirsute, with 6‒8 mm long hairs on branches, branchlets, leaf blade, petioles, and calyx (not tomentose with 2‒3 mm long hairs) and drupes with five pyrenes (not. four pyrenes). Lasianthus sithammaratensis resembles L. appressus but differs in having calyx cupular (not campanulate) and drupes with 4‒5 pyrenes (not eight). Among the Thai Lasianthus, four names are reduced to synonymy, one species was transferred to the genus Paralasianthus and excluded from Thai Lasianthus. Here, a key for the identification to all Thai Lasianthus species, as well as their nomenclature, lists of specimens examined, and notes on distribution and affinities, are provided.