bluuebunny/crossref_metadata_2025 huggingface dataset:
Sexual Dimorphism of Gut Microbiota Dictates Therapeutics Efficacy of Radiation Injuries
Authors: Cui Ming , Xiao Huiwen , Li Yuan , Zhang Shuqin , Dong Jiali , Wang Bin , Zhu Changchun , Jiang Mian , Zhu Tong , He Junbo , Wang Haichao , Fan Saijun
Published: August 2019

Accidental or iatrogenic ionizing radiation exposure precipitates acute and chronic radiation injuries. The traditional paradigm of mitigating radiotherapy‐associated adverse side effects has ignored the gender‐specific dimorphism of patients' divergent responses. Here, the effects of sexual dimorphism on curative efficiencies of therapeutic agents is examined in murine models of irradiation injury. Oral gavage of simvastatin ameliorates radiation‐induced hematopoietic injury and gastrointestinal tract dysfunction in male mice, but adversely deteriorates these radiation syndromes in female animals. In a sharp contrast, feeding animals with high‐fat diet (HFD) elicites explicitly contrary results. High‐throughput sequencing of microbial 16S rRNA, host miRNA, and mRNA shows that simvastatin or HFD administration preventes radiation‐altered enteric bacterial taxonomic structure, preserves miRNA expression profile, and reprogrammes the spectrum of mRNA expression in small intestines of male or female mice, respectively. Notably, faecal microbiota transplantation of gut microbes from opposite sexual donors abrogates the curative effects of simvastatin or HFD in respective genders of animals. Together, these findings demonstrate that curative efficiencies of therapeutic strategies mitigating radiation toxicity might be dependent on the gender of patients, thus simvastatin or HFD might be specifically useful for fighting against radiation toxicity in a sex‐dependent fashion partly based on sex‐distinct gut microbiota composition in preclinical settings.
The CRISPR‐Cas13a Gene‐Editing System Induces Collateral Cleavage of RNA in Glioma Cells
Authors: Wang Qixue , Liu Xing , Zhou Junhu , Yang Chao , Wang Guangxiu , Tan Yanli , Wu Ye , Zhang Sijing , Yi Kaikai , Kang Chunsheng
Published: August 2019

RNA is rarely used as a therapeutic target due to its flexible structure and instability. CRISPR‐Cas13a is a powerful tool for RNA knockdown, and the potential application of CRISPR‐Cas13a in cancer cells should be further studied. In this study, overexpression of LwCas13a by lentivirus in glioma cells reveals that crRNA‐EGFP induces a “collateral effect” after knocking down the target gene in EGFP‐expressing cells. EGFRvIII is a unique EGFR mutant subtype in glioma, and the CRISPR‐Cas13a system induces death in EGFRvIII‐overexpressing glioma cells. Bulk and single‐cell RNA sequencing analysis in U87‐Cas13a‐EGFRvIII cells confirm the collateral effect of the CRISPR‐Cas13a system. Furthermore, CRISPR‐Cas13a inhibits the formation of glioma intracranial tumors in mice. The results demonstrate the collateral effect of the CRISPR‐Cas13a system in cancer cells and the powerful tumor‐eliminating potential of this system.
Spin‐Momentum Locking in the Gate Tunable Topological Insulator BiSbTeSe2 in Non‐Local Transport Measurements
Authors: Voerman Joris A. , Li Chuan , Huang Yingkai , Brinkman Alexander
Published: August 2019

The helical spin‐momentum locking of an electron in a topological surface state is a feature excellently suited for the use in spintronic applications. Devices are fabricated that allow to generate, transport, and detect the spin‐polarization coming from an electronic current in the topological surface state of BiSbTeSe2; a topological insulator reported to have a negligible bulk contribution to its conduction. The successful creation of such a device is described, as is a study of the generated spin‐polarized current as the BiSbTeSe2 surface state is gated through its Dirac point. A non‐local voltage difference across separated ferromagnetic leads is observed, larger than previously reported in literature. The spin‐polarization has a maximum when the Fermi level crosses the Dirac point.
Developmental and epileptic encephalopathy in two siblings with a novel, homozygous missense variant in SCN1B
Authors: Darras Natasha , Ha Thoa K. , Rego Shannon , Martin Pierre‐Marie , Barroso Eva , Slavotinek Anne M. , Cilio Maria R.
Published: August 2019

Developmental and epileptic encephalopathies are genetic disorders in which both the developmental disability and the frequent epileptic activity are the effect of a specific gene variant. While heterozygous variants in SCN1B have been described in families with generalized epilepsy with febrile seizures plus, Type 1, only three cases of homozygous, missense variants in SCN1B have been reported in association with autosomal recessive inheritance of a severe developmental and epileptic encephalopathy. We present two siblings who are homozygous for a novel, missense variant in SCN1B, c.265C>T, predicting p.Arg89Cys. The proband is an 11‐year‐old female with infantile‐onset, fever‐induced, intractable generalized tonic–clonic seizures, myoclonic seizures, and developmental slowing and autism spectrum disorder occurring later in the course of the disease. Her 4‐year‐old brother had a similar epilepsy phenotype, but still displays normal development. This variant has not been previously reported in the homozygous state in control databases. The variant was predicted to be damaging and occurred in the vicinity of other epileptic encephalopathy‐associated missense variants that are biallelic and located in the extracellular immunoglobulin loop domain of the protein, which mediates interaction of the beta‐1 subunit with cellular adhesion molecules. Our report is the first set of siblings with homozygosity for the p.Arg89Cys variant in SCN1B and further implicates biallelic mutations in this gene as a cause of epileptic encephalopathy mimicking Dravet syndrome. Interestingly, the phenotype we observed was milder compared to that previously described in patients with recessive SCN1B mutations.
Nutritional composition of the diet of the western gorilla (Gorilla gorilla): Interspecific variation in diet quality
Authors: Lodwick Jessica L. , Salmi Roberta
Published: August 2019

To meet nutritional needs, primates adjust their diets in response to local habitat differences, though whether these dietary modifications translate to changes in dietary nutrient intake is unknown. A previous study of two populations of the mountain gorilla (MG: Gorilla beringei) found no evidence for intraspecific variation in the nutrient composition of their diets, despite ecological and dietary differences between sites. One potential explanation is that nutritional variability in primate diets requires greater ecological divergence than what was captured between MG sites, underpinning environmental differences in the nutrient quality of plant foods. To test whether Gorilla exhibits interspecific variation in dietary composition and nutrient intake, we studied the composition and macronutrients of the western gorilla (WG: Gorilla gorilla) staple diets and compared them with published data from the two MG populations. We recorded feeding time and food intake of four adult female WGs from one habituated group over a period of 11 months (December 2004–October 2005) at the Mondika Research Center, Republic of Congo, allowing for assessment of seasonal patterns of nutrient intake. Staple diets of WGs and MGs diverged in their dietary and macronutrient composition. Compared to MGs, the staple diet of WGs (by intake) contained higher proportions of fruit (43%) and leaf (12%) and a lower proportion of herb (39%), resulting in a higher intake of total nonstructural carbohydrate and fiber and a lower intake of crude protein. Staple gorilla fruits and herbs differed in nutrient quality between sites. Gorillas exhibit nutritional flexibility that reflects ecological variation in the nutrient quality of plant foods. Since dietary quality typically affects rates of growth and reproduction in primates, our results suggest that interspecific differences in nutrient intake and food quality may shape differences in gorilla nutrient balancing and female life history strategies.
Mildred Dresselhaus and Solid State Pedagogy at MIT
Authors: Martin Joseph D.
Published: August 2019

Mildred Dresselhaus is known for her influential research on the physics of carbon. Her wide‐ranging influence as a physics teacher, although well‐known to her students, has been less thoroughly examined. Exploring how Dresselhaus grew into her role teaching solid state physics at MIT reveals much about how that subfield evolved.
Cobalt‐Catalyzed Asymmetric Hydrogenation of C=N Bonds Enabled by Assisted Coordination and Nonbonding Interactions
Authors: Hu Yanhua , Zhang Zhenfeng , Zhang Jian , Liu Yangang , Gridnev Ilya D. , Zhang Wanbin
Published: August 2019

An efficient cobalt‐catalyzed asymmetric hydrogenation of C=N bonds has been realized. Chiral hydrazines were obtained in high yields and with excellent enantioselectivities (95–98 % ee). The hydrogenation went smoothly at up to 2000 substrate/catalyst and on a gram scale. The success of this reaction relies on the presence of an NHBz group in the substrates, with the reactivity and enantioselectivity improved by an assisted coordination to the cobalt atom and a nonbonding interaction with the ligand. Furthermore, this reaction has practical applications for the synthesis of several useful chiral nitrogen‐containing compounds.
An AIE‐Based Probe for Rapid and Ultrasensitive Imaging of Plasma Membranes in Biosystems
Authors: Shi Lei , Liu Yan‐Hong , Li Kun , Sharma Amit , Yu Kang‐Kang , Ji Myung Sun , Li Ling‐Ling , Zhou Qian , Zhang Hong , Kim Jong Seung , Yu Xiao‐Qi
Published: August 2019

The abnormality of the plasma membrane (PM) is an important biomarker for cell status and many diseases. Hence, visualizing the PM, especially in complex systems, is an emerging field in the life sciences, especially in low‐resource settings. Herein, we developed a water‐soluble PM‐specific probe utilizing electrostatic and hydrophobic interaction strategies with aggregation‐induced emission as the signal output. The probe could image the PM with many advanced features (wash‐free, ultrafast staining process, excellent PM specificity, and good biocompatibility), which were demonstrated by the PM imaging of neurons. The probe allowed for the first time the imaging of erythrocytes in the complex brain environment through a fluorescence‐based method. Moreover, the PM of the epidermal and partial view of the eyeball structure of live zebrafish are also revealed.
Exact Maximum Likelihood Estimates of Cox's Regression Parameters Based on Categorized Factorial Data
Authors: D'Amico F. , Rao B. R.
Published: August 2019

This paper describes how Cox's Proportional Hazards model may be used to analyze dichotomized factorial data obtained from a right‐censored epidemiological study where time to response is of interest. Exact maximum likelihood estimates of the relative mortality rates are obtained for any number of prognostic factors, as well as their joint asymptotic sampling distribution. These rates represent excess mortality due to the various levels of the prognostic factors. The results are used to discuss the effect of the factors on the survival probability distribution of a cohort of industrial workers who have been exposed to a carcinogen. Kaplan‐Meier estimates of the survival function of the internal control population are used to determine the expected number of deaths in the study population. This method differs from the usual lite‐table procedure. Asymptotic tests are proposed for some simultaneous and conditional statistical hypotheses.
An Approximation to the Bayes Optimal Multi‐Stage Design in the Colton Model for Clinical Trials
Authors: Langenberg P. , Srinivasan R.
Published: August 2019

A simple and operationally convenient approximation is proposed for the Bayes optimal multistage design within the Colton decision‐theoretic model for the comparison of two medical treatments. The two‐ and three‐stage designs are developed in full; the latter is found to be superior to several existing designs including some involving sequential adaptive sampling.
Analysing Proportions that Arise from Factorial Experiments when the Underlying Proportions are Heterogeneous Within Groups
Authors: Brooks R. J.
Published: August 2019

The analysis of proportions that arise from experiments that involve several factors is considered when there is heterogeneity of the underlying proportions within each combination of the levels of the factors. An analysis is described which can be implemented using a standard statistical program. This also provides an approximate analysis when the data are assumed to be Beta‐binomially distributed.
Testing Significant Homogeneities Within Binary Information Strings
Authors: Buser Mauro W.
Published: August 2019

In a previous paper (Buser, 1982) a nonparametric test has been presented for deciding whether or not a binary coded taxonomic node is significantly homogeneous. In the following tables the corresponding critical values, both for the one and two tailed test, are given.
Some Results for the Normal Manova Linear Functional Relationships Model
Authors: Shah A. C
Published: August 2019

Given the normal multivariate linear regression model Y = BX + E, with B subjected to the linear restrictions H BJ = W A, J known, W and H unknown, A known, the maximum likelihood estimates of H, B, W, are obtained. A likelihood ratio test criterion for testing H = H0, W = W0 is provided. The results are extended to the GMANOVA model. All results are obtained in terms of the original variates directly, unlike Healy (1980) who obtains the results for the MANOVA model in terms of the canonical transformations of the original variates.
Luminescence properties of a novel red phosphor 6LaPO4–3La3PO7–2La7P3O18:Eu3+
Authors: Liu Ru , Wang Xigui
Published: August 2019

Eu3+‐doped 6LaPO4–3La3PO7–2La7P3O18 red luminescent phosphors were synthesized by co‐deposition and high‐temperature solid‐state methods and its polyphase state was confirmed by X‐ray diffraction analysis. Transmission electron microscopy showed the grain morphology as a mixture of rods and spheres. Luminescence properties of the phosphor were investigated and its red emission parameters were evaluated as a function of Eu3+ concentration (3.00–6.00 mol%). Excitation spectra of 6LaPO4–3La3PO7–2La7P3O18:Eu3+ showed strong absorption bands at 280, 395, and 466 nm, while the luminescence spectra exhibited prominent red emission peak centred at 615 nm (5D0→7F2) in the red region. CIE chromaticity coordinates of the 6LaPO4–3La3PO7–2La7P3O18:5%Eu3+ phosphor were (0.668, 0.313) in the red region, and defined its potential application as a red phosphor.
Adopted children who kill their adoptive parents
Authors: Hubbell James T. , Heide Kathleen M. , Khachatryan Norair
Published: August 2019

The killing of parents, frequently referred to as parricide, is a disturbing phenomenon that often generates widespread media coverage. Most of the scholarly literature on this topic has focused on biological offspring who kill mothers and fathers. Some analyses have examined juveniles and adults who kill their stepparents. To date, virtually no research exists on children who kill their adoptive parents because this type of victim–offender relationship has been absent from available homicide databases, thereby preventing such analyses. The present study is a content analysis of news reports of 46 cases of adopted children who killed their adoptive parents in several different countries. Data pertaining to offender and victim demographics, incident characteristics, and the processing of offenders from the initial charge through conviction and sentencing are examined. To the extent possible, media accounts are used to classify cases according to motives or circumstances leading to the killings. The article concludes with a comparison of profiles of children who kill adoptive parents in relation to those who kill biological parents, important observations that emerged from these news accounts, and discussion of possible explanations of parricide by adopted children, including adopted children syndrome, reactive attachment disorder, and biological risk factors. Limitations of this study and directions for future research are addressed.
Optimization of chemoenzymatic Baeyer–Villiger oxidation of cyclohexanone to ε‐caprolactone using response surface methodology
Authors: Zhang Yuanyuan , Jiang Weiwei , Lv Kuiying , Sun Yangjian , Gao Xin , Zhao Qiuxiang , Ren Wenjie , Wang Fanye , Liu Junhong
Published: August 2019

ε‐Caprolactone (ε‐CL) has attracted a great deal of attention and a high product concentration is of great significance for reducing production cost. The optimization of ε‐CL synthesis through chemoenzymatic Baeyer–Villiger oxidation mediated by immobilized Trichosporon laibacchii lipase was studied using response surface methodology (RSM). The yield of ε‐CL was 98.06% with about 1.2 M ε‐CL concentration that has a substantial increase mainly due to both better stability of the cross‐linked immobilized lipase used and the optimum reaction conditions in which the concentration of cyclohexanone was 1.22 M, the molar ratio of cyclohexanone:urea hydrogen peroxide (UHP) was 1:1.3, and the reaction temperature was 56.5°C. Based on our experimental results, it can be safely concluded that there are three reactions in this reaction system, not just two reactions, in which the third reaction is that the acetic acid formed reacts with UHP to form peracetic acid in situ catalyzed by the immobilized lipase. A quadratic polynomial model based on RSM experimental results was developed and the R2 value of the equation is 0.9988, indicating that model can predict the experimental results with high precision. The experimental results also show that the molar ratio of cyclohexanone to UHP has very significant impact on the yield of ε‐CL (p < .0006).
Silica‐Supported MnII Sites as Efficient Catalysts for Carbonyl Hydroboration, Hydrosilylation, and Transesterification
Authors: Ghaffari Behnaz , Mendes‐Burak Jorge , Chan Ka Wing , Copéret Christophe
Published: August 2019

Manganese, the third most abundant transition‐metal element after iron and titanium, has recently been demonstrated to be an effective homogeneous catalyst in numerous reactions. Herein, the preparation of silica‐supported MnII sites is reported using Surface Organometallic Chemistry (SOMC), combined with tailored thermolytic molecular precursors approach based on Mn2[OSi(OtBu)3]4 and Mn{N(SiMe3)2}2⋅THF. These supported MnII sites, free of organic ligands, efficiently catalyze numerous reactions: hydroboration and hydrosilylation of ketones and aldehydes as well as the transesterification of industrially relevant substrates.
Membrangestützte Flüssig/Flüssig‐Extraktion – Wo stehen wir heute?
Authors: Riedl Wolfgang
Published: August 2019

Dank Weiterentwicklungen in den Materialwissenschaften und der Fertigungstechnik stehen heute Membranen für stabile Flüssig/Flüssig‐Extraktionsprozesse zur Verfügung. Mit rigorosen Berechnungsmodellen lassen sich sowohl die für eine Trennaufgabe erforderlichen Membranflächen berechnen als auch Optimierungen der Modulform durchführen. In Schnelltests können die prinzipielle Eignung sowie kinetische Parameter ermittelt werden. Damit sind die Voraussetzungen geschaffen, die spezifischen Vorteile dieser Trenntechnik im technischen Einsatz nutzen zu können.
A 3‐Part Phase 1 Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DSP‐6952 in Healthy Japanese Subjects and Those With ≤3 Spontaneous Bowel Movements per Week
Authors: Yumizaki Takuya , Maeda Mika , Fujita Tomoe , Kakuyama Hiroyoshi , Kumagai Yuji
Published: August 2019

We hypothesized that DSP‐6952, a partial agonist of the 5‐hydroxytryptamine type‐4 receptor and a gastrointestinal prokinetic agent, can induce natural bowel movements by enhancing gastrointestinal motility and colonic transit in patients with chronic constipation and irritable bowel syndrome with constipation. This 3‐part phase 1 study evaluated the safety, tolerability, and pharmacokinetic and pharmacodynamic profiles of DSP‐6952. Eighty‐eight Japanese subjects (64 healthy volunteers and 24 subjects with spontaneous bowel movements ≤3 times/wk) were randomized to DSP‐6952 or placebo. The overall incidence of treatment‐emergent adverse events (TEAEs) was similar for DSP‐6952 and placebo. The most frequent TEAEs were gastrointestinal disorders; diarrhea was more common with DSP‐6952, but only when it was administered to healthy volunteers. Peak plasma concentration (Cmax) and area under the concentration‐time curve (AUC) of DSP‐6952 were dose‐proportional within a range of 4‐120 mg. Under fed conditions, the Cmax and AUC of DSP‐6952 were approximately half those of fasting conditions. No abnormal drug accumulation was observed with repeated administration. In subjects with spontaneous bowel movements ≤3 times/wk, the median change in the frequency of bowel movements from baseline increased, although the difference did not reach statistical significance. DSP‐6952 was well tolerated at single and multiple doses up to 120 mg/d, with a linear pharmacokinetic profile among all subjects.
Synthesis of low‐complexity mechanical networks with constrained element values
Authors: Wang Kai , Ji Xiaofu , Hu Yinlong
Published: August 2019

This paper investigates the synthesis problem of one‐port mechanical networks consisting of one damper, one inerter, and a finite number of springs, where the damping coefficient and inertance are some values in given intervals. Due to the construction limitation, the element values of dampers and inerters are usually required to be constrained in certain ranges instead of any positive values. A necessary and sufficient condition is derived for any positive‐real admittance to be realizable as such class of networks, which is in terms of the coefficients of the admittance and the upper and lower bounds of element value constraints. Moreover, the corresponding synthesis procedure is presented based on the derivation process and realizations of three‐port spring networks. Finally, numerical examples are given for illustration. The results of this paper can be utilized in the design of inerter‐based mechanical control systems.
Dyslexia Augusti: Does Suetonius describe a pattern of signs consistent with dyslexia?
Authors: O'Sullivan David , Hammond Sean
Published: August 2019

It is generally agreed that Morgan was the first to reliably describe dyslexia with the case of Percy F. However, Suetonius, in “The lives of the twelve Caesars” describes the Emperor Augustus as having a range of language and literacy difficulties that could be consistent with this diagnosis. Using the framework of cognitive psychology, which rarely comments on the historical record, this article argues that Suetonius describes both signs and compensating strategies typical of an adult with remediated developmental dyslexia. If accepted, this analysis would locate a possible coherent description of the condition back to the second century CE.
Intraguild predation enables coexistence of competing phytoplankton in a well‐mixed water column
Authors: Moeller Holly V. , Neubert Michael G. , Johnson Matthew D.
Published: August 2019

Resource competition theory predicts that when two species compete for a single, finite resource, the better competitor should exclude the other. However, in some cases, weaker competitors can persist through intraguild predation, that is, by eating their stronger competitor. Mixotrophs, species that meet their carbon demand by combining photosynthesis and phagotrophic heterotrophy, may function as intraguild predators when they consume the phototrophs with which they compete for light. Thus, theory predicts that mixotrophy may allow for coexistence of two species on a single limiting resource. We tested this prediction by developing a new mathematical model for a unicellular mixotroph and phytoplankter that compete for light, and comparing the model's predictions with a laboratory experimental system. We find that, like other intraguild predators, mixotrophs can persist when an ecosystem is sufficiently productive (i.e., the supply of the limiting resource, light, is relatively high), or when species interactions are strong (i.e., attack rates and conversion efficiencies are high). Both our mathematical and laboratory models show that, depending upon the environment and species traits, a variety of equilibrium outcomes, ranging from competitive exclusion to coexistence, are possible.
Exploring Main Group Metal Borosulfates: Similarities and Differences of Two New Borosulfates M[B2O(SO4)3] (M = Sr, Pb)
Authors: Netzsch Philip , Gross Peter , Takahashi Hirotaka , Lotfi Sogol , Brgoch Jakoah , Höppe Henning A.
Published: August 2019

The first strontium borosulfate Sr[B2O(SO4)3] and a novel lead borosulfate Pb[B2O(SO4)3] were obtained by solvothermal reaction of the respective anhydrous metal chlorides MCl2 (M = Sr, Pb) with H[B(HSO4)4] at 300 °C. The crystal structure of Sr[B2O(SO4)3] [Pnma, Z = 4, a = 1657.38(27) pm, b = 1203.68(19) pm, c = 439.484(8) pm] is isotypic with Ba[B2O(SO4)3] and consists of chains, built up by three membered rings of two borate tetrahedra and a sulfate tetrahedron. These rings are further connected via corner‐sharing sulfate tetrahedra and hence can be classified as loop branched zweier double chains. Pb[B2O(SO4)3] crystallizes in a new structure type [P21/m, Z = 2, a = 440.00(2) pm, b = 1210.19(5) pm, c = 860.43(4) pm, β = 103.587(2) °] closely related to Sr[B2O(SO4)3]. Both structures share the common supergroup Pnmm and basically differ by the orientation of adjacent anionic chains. The coordination surrounding of Pb2+ indicates a lone pair activity and DFT calculations confirmed a weak polarizability. Moreover, the compounds were characterized by electrostatic calculations, vibrational spectroscopy and thermal analysis and broaden the structural and chemical diversity of borosulfates.
SGXPool: Improving the performance of enclave creation in the cloud
Authors: Li Dingding , Lin Ronghua , Tang Lijie , Liu Hai , Tang Yong
Published: August 2019

Deploying user data or programs in cloud risks divulging their privacy because the cloud‐side supervisors, such as system administrators, can leverage the higher privilege to snoop the user data. Based on the trusted execution environment (TEE) technology, Intel Software Guard eXtension (SGX) is a practical remedy to user privacy, which employs hardware‐assisted enclave to wrap the sensitive data, preventing them from the disclosure. However, the application performance is hurt due to the CPU‐expensive and frequent operations on the enclave creation and destruction. In this paper, we propose SGXPool, an application‐level framework of resource management to relieve the above issue. SGXPool first uses a preallocated resource pool to assign/revoke the enclave on demand and avoids its cost of dynamical creation and destruction. Then, SGXPool utilizes another resource pool to constrain the threading overhead such as thread initialization, scheduling, and destruction. In addition, SGXPool exposes the simple and clear interface, allowing users or programmers to apply SGXPool without any intrusive modifications on the original SGX application. We implement SGXPool in the typical web servers which use the multithreading to handle the concurrent user requests. The evaluation results show that SGXPool can improve the performance of the original multithreading system up to 19 times. Meanwhile, the original security of SGX is maintained.
Synergies in offshore wind and oil industry for carbon capture and utilization
Authors: Gondal Irfan Ahmad , Masood Syed Athar
Published: August 2019

The concentration of greenhouse gases (GHG)s and specifically CO2 continue to rise in the global environment including the atmosphere and the oceans. Oil and gas exploration in oceans and the increased probability of CO2 being destined for ocean storage have made the oceans much vulnerable to acidification and hence detrimental to the entire marine ecosystem. Offshore wind energy, along with other renewables, have the potential to lower the rate of CO2 absorption in the global eco system. Distant offshore wind farms are faced with the problem of dispatch of surplus wind power. Power‐to‐gas technology can be used to convert the offshore wind power into synthetic natural gas that can be transported through the existing network of offshore gas pipelines. The novel method has the capability to significantly reduce GHG emissions, solve the power dispatch problems of offshore wind farms, as well as reduce the oceanic environmental degradation. © 2019 Society of Chemical Industry and John Wiley & Sons, Ltd.
Appraisal of Cardiac Ejection Fraction With Liver Disease Severity: Implication in Post–Liver Transplantation Mortality
Authors: Kwon Hye‐Mee , Moon Young‐Jin , Jung Kyeo‐Woon , Park Yong‐Seok , Kim Kyoung‐Sun , Jun In‐Gu , Song Jun‐Gol , Hwang Gyu‐Sam
Published: August 2019

Background and Aims

Enhanced sympathetic nervous activation and peripheral vasodilation in end‐stage liver disease (ESLD) may limit the importance of left ventricular ejection fraction (LVEF) as an influential prognosticator. We sought to understand the LVEF and cardiac dimensions in ESLD patients in order to define the LVEF threshold to predict all‐cause mortality after liver transplantation (LT).

Approach and Results

Data were collected prospectively from the Asan LT Registry between 2008 and 2016, and outcomes were retrospectively reviewed. LVEF, end‐diastolic volume index (EDVI), and end‐diastolic elastance (Eed) were measured by preoperative echocardiography. Of 2,799 patients, 452 (16.2%) had LVEF ≤ 60%, with 29 (1.0%) having LVEF < 55% and 269 (9.6%) had LVEF ≥ 70%. Over a median of 5.4‐year follow‐up, 329 (11.8%) patients died: 104 (3.7%) died within 90 days. LVEF (range, 30%‐81%) was directly proportionate to Model for End‐stage Liver Disease (MELD) scores, an index of liver disease severity, in survivors but showed a fixed flat‐line pattern in nonsurvivors (interaction P = 0.004 between groups), with lower EDVI (P = 0.013) and higher Eed (P = 0.001) in the MELD ≥ 20 group. Patients with LVEF ≤ 60% had higher 90‐day (13% vs. 7.4%; log rank, P = 0.03) and median 5.4‐year (26.7% vs. 16.2%; log rank, P = 0.003) mortality rates in the MELD ≥ 20 group, respectively, compared to those with LVEF > 60%. Specifically, in the MELD > 35 group, median 5.4‐year mortality rate was 53.3% in patients with LVEF ≤ 60% versus 24% in those with LVEF > 60% (log rank P < 0.001). By contrast, mortality rates of LVEF ≤ 60% and > 60% were similar in the MELD < 20 group (log rank P = 0.817).

Conclusions

LVEF ≤ 60% is strongly associated with higher post‐LT mortality rates in the MELD ≥ 20 group, indicating the need to appraise both LVEF and liver disease severity simultaneously. Enhanced diastolic elastance with low EDVI provides insights into pathogenesis of low LVEF in nonsurvivors with MELD ≥ 20.
Comparison between thrombotic risk scores in essential thrombocythemia and survival implications
Authors: Santoro M. , Accurso V. , Mancuso S. , Carlisi M. , Raso S. , Tarantino G. , Di Piazza F. , Perez A. , Russo A. , Siragusa S.
Published: August 2019

The conventional thrombotic risk stratification in essential thrombocythemia (ET) distinguishes patients in two risk groups based on previous thrombosis and age (< or >60). The IPSET‐thrombosis takes into account four risk factors: age greater than 60 years and the presence of CV risk factors, thrombosis history and JAK2 V617F presence. The revised IPSET‐thrombosis uses three adverse variables to delineate four risk categories: age greater than 60, thrombosis history, and JAK2 V617F presence. We compared different risk models in the estimation of thrombotic risk in 191 patients with ET and the role of specific driver mutations affecting overall survival, according to thrombotic risk. We also evaluated the mutational status of patients showing history of thrombosis or cardiovascular events versus patients who did not. Finally, we verified whether the thrombotic risk had a significant impact on survival in our ET patients. The data analysis has been performed through the conventional statistics and overall survival estimated by using the Kaplan‐Meyer method. Interestingly, either using the traditional system for thrombotic risk or the IPSET‐t prognostic score or the current stratification for the thrombotic risk, high‐risk patients are always highly represented. This evidence is of note, being the high‐risk category indicated for cytoreduction, affecting quality of life, despite the good overall prognosis of patients with ET diagnosis in general. The analysis of overall survival in our patients, according to different models for thrombotic risk, highlighted the poor prognosis of high‐risk patients compared with those with a lower thrombotic risk, in particular when using traditional stratification and current stratification. In conclusion, the occurrence of thrombotic or cardiovascular events represents one of the most severe complications at diagnosis or during follow‐up of ET despite current recommendations, having a significant impact on morbidity and survival.
Entropy generation analysis of convective airflow in a solar updraft tower power plant
Authors: Tayebi Tahar
Published: August 2019

The main objective of this numerical investigation is to interpret the entropy generation for free convection airflow in a solar tower updraft system. The ground surface is subjected to uniform hot temperature and the collector cover is maintained at lower constant temperature while the chimney wall is adiabatic. Two dimensionless equations of steady laminar free convective airflow are discretized using the finite volume approach. Numerical solutions were accomplished for different values of the Rayleigh number. Results are given in terms of isotherms, velocity magnitude, local entropy generation associated with thermal and fluid friction, local total entropy generation and local Bejan number contours for Rayleigh number ranging between 103 and 108. The reported results show that thermal and frictional irreversibilities are proportional to the Rayleigh number. Also, it was found that, at lower Rayleigh, total irreversibility is attributable to the thermal irreversibilities and occurs essentially in the collector section. At higher Rayleigh, frictional irreversibilities are increased significantly and become the dominant source of irreversibility in the solar tower, and the chimney section is the main contributor in the total irreversibility in the system.
Pharmacological inhibition of the MEK5/ERK5 and PI3K/Akt signaling pathways synergistically reduces viability in triple‐negative breast cancer
Authors: Wright Thomas D. , Raybuck Christopher , Bhatt Akshita , Monlish Darlene , Chakrabarty Suravi , Wendekier Katy , Gartland Nathan , Gupta Mohit , Burow Matthew E. , Flaherty Patrick T. , Cavanaugh Jane E.
Published: August 2019

Triple‐negative breast cancers (TNBCs) represent 15% to 20% of all breast cancers and are often associated with poor prognosis. The lack of targeted therapies for TNBCs contributes to higher mortality rates. Aberrations in the phosphoinositide‐3‐kinase (PI3K) and mitogen‐activated protein kinase pathways have been linked to increased breast cancer proliferation and survival. It has been proposed that these survival characteristics are enhanced through compensatory signaling and crosstalk mechanisms. While the crosstalk between PI3K and extracellular signal‐regulated kinase 1/2 (ERK1/2) pathways has been characterized in several systems, new evidence suggests that MEK5/ERK5 signaling is a key component in the proliferation and survival of several aggressive cancers. In this study, we examined the effects of dual inhibition of PI3K/protein kinase B (Akt) and MEK5/ERK5 in the MDA‐MB‐231, BT‐549, and MDA‐MB‐468 TNBC cell lines. We used the Akt inhibitor ipatasertib, ERK5 inhibitors XMD8‐92 and AX15836, and the novel MEK5 inhibitor SC‐1‐181 to investigate the effects of dual inhibition. Our results indicated that dual inhibition of PI3K/Akt and MEK5/ERK5 signaling was more effective at reducing the proliferation and survival of TNBCs than single inhibition of either pathway alone. In particular, a loss of Bad phosphorylation at two distinct sites was observed with dual inhibition. Furthermore, the inhibition of both pathways led to p21 restoration, decreased cell proliferation, and induced apoptosis. In addition, the dual inhibition strategy was determined to be synergistic in MDA‐MB‐231 and BT‐549 cells and was relatively nontoxic in the nonneoplastic MCF‐10 cell line. In summary, the results from this study provide a unique prospective into the utility of a novel dual inhibition strategy for targeting TNBCs.
Results From a First‐in‐Human Study of BNZ‐1, a Selective Multicytokine Inhibitor Targeting Members of the Common Gamma (γc) Family of Cytokines
Authors: Frohna Paul A. , Ratnayake Anoshie , Doerr Nick , Basheer Asjad , Al‐Mawsawi Laith Q. , Kim Woo Jae , Zapata Juan C. , Wu Xiaorong , Waldmann Thomas A. , Azimi Nazli , Tagaya Yutaka
Published: August 2019

Pathologic roles of interleukin (IL)‐2, IL‐9, and IL‐15, have been implicated in multiple T‐cell malignancies and autoimmune diseases. BNZ‐1 is a selective and simultaneous inhibitor of IL‐2, IL‐9, and IL‐15, which targets the common gamma chain signaling receptor subunit. In this first‐in‐human study, 18 healthy adults (n = 3/cohort) received an intravenous dose of 0.2, 0.4, 0.8, 1.6, 3.2, or 6.4 mg/kg infused over ≤5 minutes on day 1 and were followed for 30 days for safety and pharmacokinetic/pharmacodynamic sample collection. No dose‐limiting toxicities, infusion reactions, or serious or severe treatment‐emergent adverse events were observed. Headache was the only treatment‐emergent adverse event in >1 subject (n = 3). Peak and total BNZ‐1 exposure was generally dose proportional, with a terminal elimination half‐life of ∼5 days. Pharmacodynamic effects of BNZ‐1 on regulatory T cells (Tregs, IL‐2), natural killer (NK) cells (IL‐15) and CD8 central memory T cells (Tcm, IL‐15) were measured by flow cytometry and used to demonstrate target engagement. For Tregs, 0.2 mg/kg was an inactive dose, while a maximum ∼50% to 60% decrease from baseline was observed on day 4 after doses of 0.4 to 1.6 mg/kg, and higher doses produced an 80% to 93% decrease from baseline on day 15. Similar pharmacodynamic trends were observed for natural killer cells and CD8 Tcm, although decreases in CD8 Tcm were more prolonged. These subpopulations returned to/toward baseline by day 31. T cells (total, CD4, and CD8), B cells, and monocytes were unchanged throughout. These preliminary results suggest that BNZ‐1 safely and selectively inhibits IL‐2 and IL‐15, which results in robust, reversible immunomodulation.
Impact assessment and investigation of factors associated with herpesviruses viremia in the first year of renal transplantation
Authors: Savassi‐Ribas Flavia , Gomes dos Santos de Almeida Stéphanie , Baez Camila Freze , Magalhães de Souza Leandro , Wagner Tereza Cristina Simão , Matuck Tereza Azevedo , Monteiro de Carvalho Deise De Boni , Marandino Guimarães Maria Angelica Arpon , Varella Rafael Brandão
Published: August 2019

The increased risk for opportunistic infections after a renal transplant requires monitoring of viral infections to avoid future complications. Our goal was to investigate the impact and factors associated with Epstein‐Barr virus (EBV), human cytomegalovirus (HCMV) and human herpesvirus type 6 (HHV‐6) viremia in renal transplant recipients. Whole blood samples were collected monthly from 82 patients during the first semester and then quarterly up to 1 year after transplantation. EBV, HCMV, and HHV‐6 were detected and quantified by TaqMan real‐time polymerase chain reaction. The results showed that EBV and HCMV viremia were detected in 32 patients (39% each), while HHV‐6 viremia in only 3 patients (3.7%). EBV was significantly associated with age (P = .050), thymoglobuline induction (P = .019), mTOR inhibitor‐based therapy (P = .003), and female gender (P = .044). HCMV was significantly associated with basiliximab induction (P = .015), mycophenolate mofetil (MMF)‐based therapy (P = .003) and allograft acute rejection (P = .033). Moreover, HCMV‐disease was correlated with MMF‐based therapy (P = .021) and female gender (P = .003). In conclusion, EBV and HCMV viremia were associated with different immunosuppressive induction and maintenance strategies. Additionally, higher HCMV viremia (> 10
4 copies/mL) was related to acute allograft rejection.
The decision‐making process in viral marketing—A review and suggestions for further research
Authors: Reichstein Thomas , Brusch Ines
Published: August 2019

Viral marketing is used to widely distribute content. To achieve this goal, the basic decision‐making process from content reception to interaction must be clarified. This paper examines the decision‐making process of individuals in viral marketing using a new dynamic model. In addition, this work reviews the existing literature on viral marketing and structures to identify existing issues for further research. The decision‐making process is basically divided into two stages. In the first decision stage, individuals decide whether content should be considered. When individuals agree to view the content, they decide in the second stage whether they want to interact with it. These two decisions are influenced by three factors: the framework conditions, content, and interaction aims. With the help of the decision model, this paper summarizes the most important findings from viral marketing research over the last 20 years. In addition, this work provides new opportunities for further research in the field of viral marketing.
Side differences in the degree of mosaicism of the buccal mucosa in Turner syndrome
Authors: Thunström Sofia , Landin‐Wilhelmsen Kerstin , Bryman Inger , Hanson Charles
Published: August 2019

Background

The aim was to investigate if there were any differences in the degree of mosaicism between the left‐ and right‐hand sides of the buccal mucosa in women with Turner syndrome.

Methods

Buccal smears were taken on the left‐ and right‐hand sides at the same time for genetic analyses with fluorescence in situ hybridization in women with Turner syndrome, n = 20; 10 with and 10 without mosaicism based on the blood karyotype, and one control. A difference in the degree of mosaicism ≥5% between the sides was considered as an actual difference and <5% as equivalent.

Results

Of 20, 10 (50%) had ≥ 5% difference in the degree of mosaicism between the left‐ and right‐hand sides of the buccal mucosa. The mean difference was 9.1% and the median was 4.5%, range 1%–38%. The control with ordinary female karyotype had no side difference.

Conclusion

There was an intraorganic mosaicism of the buccal mucosa with a side difference in the degree of mosaicism of up to 38% in women with Turner syndrome. When mosaicism is strongly suspected, but not confirmed by the blood karyotype, it is recommended that buccal smears from both sides of the oral cavity should be analyzed.
A novel LAMP2 p.G93R mutation associated with mild Danon disease presenting with familial hypertrophic cardiomyopathy
Authors: Xu Jing , Wang Lu , Liu Xiangdong , Dai Qiming
Published: August 2019

Background

Danon disease (DD) is an X‐linked dominant multisystem disorder that is associated with cardiomyopathy, skeletal myopathy, and varying degrees of intellectual disability. It results from mutations in the lysosome‐associated membrane protein 2 (LAMP2) gene.

Methods

Herein, a proband with a mild DD case presenting with a familial hypertrophic cardiomyopathy (HCM) phenotype and additional family members were evaluated. Exome sequencing and Sanger sequencing were performed to explore the genetic basis of DD in the proband. Segregation, in silico, and functional analyses were carried out to explore potential pathogenicity in the candidate mutation.

Results

Exome sequencing and Sanger sequencing identified one novel missense mutation (p.G93R) in the LAMP2 gene in the proband, and this mutation was also identified in three other family members. In silico analysis of LAMP2 predicted that the mutation causes a conformational change and subsequent protein destabilization. Furthermore, functional examination showed that mutation carriers have a significant reduction in LAMP2 expression, which supports that the mutation is pathogenic. Moreover, skewed X chromosome inactivation (XCI) was identified in one female mutation carrier, thus suggesting that skewed XCI may be the reason why this individual escaped the pathogenic influence of the mutation.

Conclusion

These findings will aid in diagnosing DD patients carrying this LAMP2 mutation that presents with a HCM phenotype. Furthermore, this study illustrates the importance of utilizing a molecular diagnostic approach in HCM patients and is the first study to report a LAMP2 p.G93R mutation associated with mild DD and identify that XCI serves a protective role in DD etiology.
Existence, uniqueness, and numerical simulations of Föppl‐von Kármán equations for simply supported plate
Authors: Alkhayal Jana , Chehab Jean‐Paul , Jazar Mustapha
Published: August 2019

In this paper, we consider the Föppl‐von Kàrmàn equations in the case of a simply supported thin plate. We introduce a nonlinear Gauss‐Seidel fixed point scheme which allows to obtain a constructive proof of the existence and the uniqueness, when a small nonzero source term is considered. Numerical simulations are given using finite elements approximation. We point out the important role of a parameter which allows to select situations in which a buckling phenomena is observed numerically.
Compact dual‐band implantable planar inverted‐F antenna with bandwidth enhancement
Authors: Shang Jiangli , Yu Ying , Xu Li‐Jie
Published: August 2019

In this paper, a miniaturized planar inverted‐F antenna (PIFA) with a volume of 49.5 mm3 is proposed for biomedical implantable devices, operating in Medical Implant Communications Service (MICS, 402‐405 MHz) band and Industrial, Scientific, and Medical (ISM, 2.40‐2.48 GHz) band. It has a wide operating bandwidth in MICS band. The initial PIFA is designed with dual‐band performance, where the lower band is formed by quarter‐guided‐wavelength resonance and the higher band is formed by two‐guided‐wavelength resonance. Furthermore, by etching open‐slots between short and feed on the ground, a new resonance is introduced and moved towards the fundamental one, expanding the bandwidth in MICS band. Also, the introduction of slots lowers the initial resonant frequency in higher band, meeting the frequency demands of ISM band. Finally, the proposed antenna is measured in pork as well as skin‐mimicking gels, showing a bandwidth of 50.7% and 38% in MICS band, and 13.9% and 6.9% in ISM band.
A polarization reconfigurable discontinuous ring dipole antenna
Authors: Saraswat Kapil , Harish Ayyangar R.
Published: August 2019

A circularly polarized antenna is realized using a discontinuous ring dipole. With the introduction of p‐i‐n diodes, it has been possible to achieve polarization reconfigurability in the antenna. The antenna is fed by a tapered feed line, which also acts as a balun and biasing structure. The sense of rotation of the electric field vector (left‐hand or right‐hand) can be controlled by switching the states of the diodes. An equivalent circuit of the antenna is proposed, which has been used to compute the input reflection coefficient of the antenna. The performance of the antenna is verified by comparing the simulated results with the measured results. It has been observed that the antenna has 8.56% overlapping CP bandwidth (a common bandwidth for |S11| ≤ −10 dB and axial ratio, AR ≤3 dB) from 5.03to 5.48 GHz. A measured gain of 3.61 dBic is obtained for all polarization states. The proposed antenna can be used for the 5.2 GHz Wi‐Fi application.