bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation appraisal of antibiotic resistance with fecal, metal and microplastic contamination in a tropical Indian river, lakes and sewage
Authors: Ram Bhagwana , Kumar Manish
Published: February 2020

The present study compares the prevalence of antibiotic-resistant bacteria (ARB) in the urban water of Ahmedabad (India), to understand the correlation of ARB with the fecal, metal, and microplastic contamination. Eleven samples, i.e., three locations of Sabarmati River along with one sample each from two (Chandola and Kankaria) lakes, and influents and effluents from three Sewage Treatment Plants (STPs) were analyzed in this study. E. coli isolated from the samples were subjected to three fluoroquinolones (Levofloxacin (LVX), Ciprofloxacin (CIP), and Norfloxacin (NFX)) and three non-fluoroquinolones (Kanamycin Monosulphate (KM), Tetracycline (TC), and Sulfamethoxazole (ST)) antibiotics for resistance quantification. Prevalence of the E. coli in the Sabarmati River (19,467–76,600 cfu mL−1) was higher than the lakes and STP(s), except the influent sample at Juhapura STP. Among the lake samples, Kankaria Lake (KL) exhibited 0% resistance towards all six antibiotics despite 5× prevalence of E. coli than that of Chandola Lake (CL) exhibiting up to 60% resistance for non-fluoroquinolones and 40% resistance to NFX. Multivariate statistical analyses suggest that resistance for ST, KM, and TC is more prevalent and correlated with electrical conductivity (EC), finer size microplastic, manganese (Mn), and nickel (Ni), whereas the resistance for fluoroquinolones (LVX, CIP, and NFX) seems highly influenced by seasonal temperature variation. Larger size microplastic clustered with salinity, ORP, and Pb. Further, fecal contamination and antibiotic resistance seem to be governed by the same source and processes, yet it does not show good correlation except for the river samples. This result may be attributed to the dynamic river–human interface, substantial wastewater discharge into the river, stagnant water flow, and urbanization-related discharge conditions rather than the upstream condition.
Multisensory Gains in Simple Detection Predict Global Cognition in Schoolchildren
Authors: Denervaud Solange , Gentaz Edouard , Matusz Pawel J. , Murray Micah M.
Published: February 2020

The capacity to integrate information from different senses is central for coherent perception across the lifespan from infancy onwards. Later in life, multisensory processes are related to cognitive functions, such as speech or social communication. During learning, multisensory processes can in fact enhance subsequent recognition memory for unisensory objects. These benefits can even be predicted; adults’ recognition memory performance is shaped by earlier responses in the same task to multisensory – but not unisensory – information. Everyday environments where learning occurs, such as classrooms, are inherently multisensory in nature. Multisensory processes may therefore scaffold healthy cognitive development. Here, we provide the first evidence of a predictive relationship between multisensory benefits in simple detection and higher-level cognition that is present already in schoolchildren. Multiple regression analyses indicated that the extent to which a child (N = 68; aged 4.5–15years) exhibited multisensory benefits on a simple detection task not only predicted benefits on a continuous recognition task involving naturalistic objects (p = 0.009), even when controlling for age, but also the same relative multisensory benefit also predicted working memory scores (p = 0.023) and fluid intelligence scores (p = 0.033) as measured using age-standardised test batteries. By contrast, gains in unisensory detection did not show significant prediction of any of the above global cognition measures. Our findings show that low-level multisensory processes predict higher-order memory and cognition already during childhood, even if still subject to ongoing maturation. These results call for revision of traditional models of cognitive development (and likely also education) to account for the role of multisensory processing, while also opening exciting opportunities to facilitate early learning through multisensory programs. More generally, these data suggest that a simple detection task could provide direct insights into the integrity of global cognition in schoolchildren and could be further developed as a readily-implemented and cost-effective screening tool for neurodevelopmental disorders, particularly in cases when standard neuropsychological tests are infeasible or unavailable.
Proteomic analyses of sheep (ovis aries) embryonic skeletal muscle
Authors: Wang Xinyue , Shi Tianpei , Zhao Zhida , Hou Haobin , Zhang Li
Published: February 2020

The growth and development of embryonic skeletal muscle plays a crucial role in sheep muscle mass. But proteomic analyses for embryonic skeletal development in sheep had been little involved in the past research. In this study, we explored differential abundance proteins during embryonic skeletal muscle development by the tandem mass tags (TMT) and performed a protein profile analyses in the longissimus dorsi of Chinese merino sheep at embryonic ages Day85 (D85N), Day105 (D105N) and Day135 (D135N). 5,520 proteins in sheep embryonic skeletal muscle were identified, and 1,316 of them were differential abundance (fold change ≥1.5 and p-value < 0.05). After the KEGG enrichment analyses, these differential abundance proteins were significant enriched in the protein binding, muscle contraction and energy metabolism pathways. After validation of the protein quantification with the parallel reaction monitoring (PRM), 41% (16/39) significant abundance proteins were validated, which was similar to the results of protein quantification with TMT. All results indicated that D85N to D105N was the stage of embryonic muscle fibers proliferation, while D105N to D135N was the stage of their hypertrophy. These findings provided a deeper understanding of the function and rules of proteins in different phases of sheep embryonic skeletal muscle growth and development.
Porphyromonas gingivalis triggers the shedding of inflammatory endothelial microvesicles that act as autocrine effectors of endothelial dysfunction
Authors: Bugueno Isaac Maximiliano , Zobairi El-Ghazouani Fatiha , Batool Fareeha , El Itawi Hanine , Anglès-Cano Eduardo , Benkirane-Jessel Nadia , Toti Florence , Huck Olivier
Published: February 2020

A link between periodontitis and atherothrombosis has been highlighted. The aim of this study was to determine the influence of Porphyromonas gingivalis on endothelial microvesicles (EMVPg) shedding and their contribution to endothelial inflammation. Endothelial cells (EC) were infected with P. gingivalis (MOI = 100) for 24 h. EMVPg were isolated and their concentration was evaluated by prothrombinase assay. EMVPg were significantly increased in comparison with EMVCtrl shedded by unstimulated cells. While EMVCtrl from untreated EC had no effect, whereas, the proportion of apoptotic EC was increased by 30 nM EMVPg and viability was decreased down to 25%, a value elicited by P. gingivalis alone. Moreover, high concentration of EMVPg (30 nM) induced a pro-inflammatory and pro-oxidative cell response including up-regulation of TNF-α, IL-6 and IL-8 as well as an altered expression of iNOS and eNOS at both mRNA and protein level. An increase of VCAM-1 and ICAM-1 mRNA expression (4.5 folds and 3 folds respectively (p < 0.05 vs untreated) was also observed after EMVPg (30 nM) stimulation whereas P. gingivalis infection was less effective, suggesting a specific triggering by EMVPg. Kinasome analysis demonstrated the specific effect induced by EMVPg on main pro-inflammatory pathways including JNK/AKT and STAT. EMVPg are effective pro-inflammatory effectors that may have detrimental effect on vascular homeostasis and should be considered as potential autocrine and paracrine effectors involved in the link between periodontitis and atherothrombosis.
Association of past dengue fever epidemics with the risk of Zika microcephaly at the population level in Brazil
Authors: Carvalho Marilia Sá , Freitas Laís Picinini , Cruz Oswaldo Gonçalves , Brasil Patrícia , Bastos Leonardo Soares
Published: February 2020

Despite all the research done on the first Zika virus (ZIKV) epidemics, it was only after the Brazilian epidemic that the Congenital Zika Syndrome was described. This was made possible due to the large number of babies born with microcephaly in the Northeast region (NE) in a narrow time. We hypothesize that the fivefold difference in the rate of microcephalic neonates between the NE and other regions is partially an effect of the population prior immunity against Dengue viruses (DENV), that cross-react with ZIKV. In this ecological study, we analysed the interaction between dengue fever epidemics from 2001 to 2014 and the 2015/2016 microcephaly epidemic in 400 microregions in Brazil using random-effects models under a Bayesian approach. The estimated effect of the time lag between the most recent large dengue epidemic (>400/100,000 inhabitants) and the microcephaly epidemic ranged from protection (up to 6 years prior) to an increased risk (from 7 to 12 years). This sustained window of protection, larger than described in previous longitudinal studies, is possibly an effect of herd immunity and of multiple exposures to DENV that could boost immunity.
RyR1-targeted drug discovery pipeline integrating FRET-based high-throughput screening and human myofiber dynamic Ca2+ assays
Authors: Rebbeck Robyn T. , Singh Daniel P. , Janicek Kevyn A. , Bers Donald M. , Thomas David D. , Launikonis Bradley S. , Cornea Razvan L.
Published: February 2020

Elevated cytoplasmic [Ca2+] is characteristic in severe skeletal and cardiac myopathies, diabetes, and neurodegeneration, and partly results from increased Ca2+ leak from sarcoplasmic reticulum stores via dysregulated ryanodine receptor (RyR) channels. Consequently, RyR is recognized as a high-value target for drug discovery to treat such pathologies. Using a FRET-based high-throughput screening assay that we previously reported, we identified small-molecule compounds that modulate the skeletal muscle channel isoform (RyR1) interaction with calmodulin and FK506 binding protein 12.6. Two such compounds, chloroxine and myricetin, increase FRET and inhibit [3H]ryanodine binding to RyR1 at nanomolar Ca2+. Both compounds also decrease RyR1 Ca2+ leak in human skinned skeletal muscle fibers. Furthermore, we identified compound concentrations that reduced leak by > 50% but only slightly affected Ca2+ release in excitation-contraction coupling, which is essential for normal muscle contraction. This report demonstrates a pipeline that effectively filters small-molecule RyR1 modulators towards clinical relevance.
Number of teeth is associated with facial size in humans
Authors: Oeschger Elias S. , Kanavakis Georgios , Halazonetis Demetrios J. , Gkantidis Nikolaos
Published: February 2020

During human evolution there has been an increase in the size of the brain and the cranium, whereas the size of the face, as well as the size and number of teeth have decreased. In modern humans, the occurrence of missing permanent teeth, namely tooth agenesis, is common. It could be attributed to a biological mechanism of tooth number reduction that has evolved during time and might still be active. Although, if evident, it would add support to this theory, the relationship between this phenotype and craniofacial size remains largely unknown. The present case-control study shows that modern individuals with tooth agenesis have indeed smaller facial configurations. For example, a 15-year-old female with no, one, or ten missing teeth would have a facial centroid size of 511.83, 510.81, or 501.70 mm, respectively. No such effect was observable in the cranial base and the cranium. Our results suggest that common gene regulatory mechanisms that have evolved over time, continue to regulate the number of teeth and facial size of modern humans in a coordinated manner. We anticipate our findings to enrich our understanding of the evolution and development of the human head and kindle future developmental research on this field.
A Nursing Care Intervention Model for Elderly People to Ascertain General Profiles of Functionality and Self Care Needs
Authors: Goes Margarida , Lopes Manuel José , Oliveira Henrique , Fonseca César , Marôco João
Published: February 2020

A core set of International Classification of Functioning, Disability and Health codes was used to ascertain general profiles of functionality as a function of biological and sociodemographic characteristics and to develop structured nursing interventions in accordance with self care deficits identified by studying self care behavior for elderly people living in both extensively and sparsely populated rural areas. Data were collected by health professionals in the participants’ houses. An exploratory factor analysis enabled reduced data dimensions, and factorial validity was assessed by a confirmatory factor analysis. An ordinal regression model was built to identify general profiles of functionality as a function of age. A bar graph was used as a measurement tool for nursing care needs as a function of self care behavior and functional profile level. No functional problems were expected among people under the age of 74 years, while mild functionality problems were expected among people older than 74 years. Regarding nursing care needs, the results of the constructed model suggested that the functional concept “Support and Relationships” is associated with higher levels of functional problems and thus a greater need for self care interventions and that people aged 85 years and older always show therapeutic self care deficits.
Nationwide prediction of type 2 diabetes comorbidities
Authors: Dworzynski Piotr , Aasbrenn Martin , Rostgaard Klaus , Melbye Mads , Gerds Thomas Alexander , Hjalgrim Henrik , Pers Tune H.
Published: February 2020

Identification of individuals at risk of developing disease comorbidities represents an important task in tackling the growing personal and societal burdens associated with chronic diseases. We employed machine learning techniques to investigate to what extent data from longitudinal, nationwide Danish health registers can be used to predict individuals at high risk of developing type 2 diabetes (T2D) comorbidities. Leveraging logistic regression-, random forest- and gradient boosting models and register data spanning hospitalizations, drug prescriptions and contacts with primary care contractors from >200,000 individuals newly diagnosed with T2D, we predicted five-year risk of heart failure (HF), myocardial infarction (MI), stroke (ST), cardiovascular disease (CVD) and chronic kidney disease (CKD). For HF, MI, CVD, and CKD, register-based models outperformed a reference model leveraging canonical individual characteristics by achieving area under the receiver operating characteristic curve improvements of 0.06, 0.03, 0.04, and 0.07, respectively. The top 1,000 patients predicted to be at highest risk exhibited observed incidence ratios exceeding 4.99, 3.52, 1.97 and 4.71 respectively. In summary, prediction of T2D comorbidities utilizing Danish registers led to consistent albeit modest performance improvements over reference models, suggesting that register data could be leveraged to systematically identify individuals at risk of developing disease comorbidities.
Inferring quantity and qualities of superimposed reaction rates from single molecule survival time distributions
Authors: Reisser Matthias , Hettich Johannes , Kuhn Timo , Popp Achim P. , Große-Berkenbusch Andreas , Gebhardt J. Christof M.
Published: February 2020

Actions of molecular species, for example binding of transcription factors to chromatin, may comprise several superimposed reaction pathways. The number and the rate constants of such superimposed reactions can in principle be resolved by inverse Laplace transformation of the corresponding distribution of reaction lifetimes. However, current approaches to solve this transformation are challenged by photobleaching-prone fluorescence measurements of lifetime distributions. Here, we present a genuine rate identification method (GRID), which infers the quantity, rates and amplitudes of dissociation processes from fluorescence lifetime distributions using a dense grid of possible decay rates. In contrast to common multi-exponential analysis of lifetime distributions, GRID is able to distinguish between broad and narrow clusters of decay rates. We validate GRID by simulations and apply it to CDX2-chromatin interactions measured by live cell single molecule fluorescence microscopy. GRID reveals well-separated narrow decay rate clusters of CDX2, in part overlooked by multi-exponential analysis. We discuss the amplitudes of the decay rate spectrum in terms of frequency of observed events and occupation probability of reaction states. We further demonstrate that a narrow decay rate cluster is compatible with a common model of TF sliding on DNA.
Altruistic food sharing behavior by human infants after a hunger manipulation
Authors: Barragan Rodolfo Cortes , Brooks Rechele , Meltzoff Andrew N.
Published: February 2020

Altruistic behavior entails giving valuable benefits to others while incurring a personal cost. A distinctively human form of altruistic behavior involves handing nutritious food to needy strangers, even when one desires the food. Engaging in altruistic food transfer, instead of keeping the food, is costly, because it reduces the caloric intake of the benefactor vis-à-vis the beneficiary. Human adults engage in this form of altruistic behavior during times of war and famine, when giving food to others threatens one’s own survival. Our closest living primate relatives, chimpanzees (Pan troglodytes) and bonobos (Pan paniscus), exhibit notable constraints on the proclivity to engage in such food transfer (particularly chimpanzees), although they share many social-cognitive commonalities with humans. Here we show that in a nonverbal test, 19-month-old human infants repeatedly and spontaneously transferred high-value, nutritious natural food to a stranger (Experiment 1) and more critically, did so after an experimental manipulation that imposed a feeding delay (Experiment 2), which increased their own motivation to eat the food. Social experience variables moderated the expression of this infant altruistic behavior, suggesting malleability.
One-step Synthesized Silver Nanoparticles Using Isoimperatorin: Evaluation of Photocatalytic, and Electrochemical Activities
Authors: Mavaei Maryamosadat , Chahardoli Azam , Shokoohinia Yalda , Khoshroo Alireza , Fattahi Ali
Published: February 2020

In the current study, isoimperatorin, a natural furanocoumarin, is used as a reducing reagent to synthesize isoimperatorin mediated silver nanoparticles (Iso-AgNPs), and photocatalytic and electrocatalytic activities of Iso-AgNPs are evaluated. Iso-AgNPs consisted of spherically shaped particles with a size range of 79–200 nm and showed catalytic activity for the degradation (in high yields) of New Fuchsine (NF), Methylene Blue (MB), Erythrosine B (ER) and 4-chlorophenol (4-CP) under sunlight irradiation. Based on obtained results, Iso-AgNPs exhibited 96.5%, 96.0%, 92%, and 95% degradation rates for MB, NF, ER, and 4-CP, respectively. The electrochemical performance showed that the as-prepared Iso-AgNPs exhibited excellent electrocatalytic activity toward hydrogen peroxide (H2O2) reduction. It is worth noticing that the Iso-AgNPs were used as electrode materials without any binder. The sensor-based on binder-free Iso-AgNPs showed linearity from 0.1 µM to 4 mM with a detection limit of 0.036 μM for H2O2. This binder-free and straightforward strategy for electrode preparation by silver nanoparticles may provide an alternative technique for the development of other nanomaterials based on isoimperatorin under green conditions. Altogether, the application of isoimpratorin in the synthesis of nano-metallic electro and photocatalysts, especially silver nanoparticles, is a simple, cost-effective and efficient approach.
Nucleus accumbens pathways control cell-specific gene expression in the medial prefrontal cortex
Authors: Hikida Takatoshi , Yao Shuhei , Macpherson Tom , Fukakusa Ayumi , Morita Makiko , Kimura Haruhide , Hirai Keisuke , Ando Tatsuya , Toyoshiba Hiroyoshi , Sawa Akira
Published: February 2020

The medial prefrontal cortex (mPFC) is a critical component of a cortico-basal ganglia-thalamo-cortical loop regulating limbic and cognitive functions. Within this circuit, two distinct nucleus accumbens (NAc) output neuron types, dopamine D1 or D2 receptor-expressing neurons, dynamically control the flow of information through basal ganglia nuclei that eventually project back to the mPFC to complete the loop. Thus, chronic dysfunction of the NAc may result in mPFC transcriptomal changes, which in turn contribute to disease conditions associated with the mPFC and basal ganglia. Here, we used RNA sequencing to analyse differentially expressed genes (DEGs) in the mPFC following a reversible neurotransmission blocking technique in D1 or D2 receptor-expressing NAc neurons, respectively (D1-RNB, or D2-RNB). Gene Set Enrichment Analysis revealed that gene sets of layer 5b and 6 pyramidal neurons were enriched in DEGs of the mPFC downregulated in both NAc D1- and D2-RNB mice. In contrast, gene sets of layer 5a pyramidal neurons were enriched in upregulated DEGs of the mPFC in D1-RNB mice, and downregulated DEGs of the mPFC in D2-RNB mice. These findings reveal for the first time that NAc output pathways play an important role in controlling mPFC gene expression.
Cyclosporine H Improves the Multi-Vector Lentiviral Transduction of Murine Haematopoietic Progenitors and Stem Cells
Authors: Olender Leonid , Bujanover Nir , Sharabi Omri , Goldstein Oron , Gazit Roi
Published: February 2020

Haematopoietic stem cells (HSCs) have the potential for lifetime production of blood and immune cells. The introduction of transgenes into HSCs is important for basic research, as well as for multiple clinical applications, because HSC transplantation is an already established procedure. Recently, a major advancement has been reported in the use of cyclosporine H (CsH), which can significantly enhance the lentivirus (LV) transduction of human haematopoietic stem and progenitor cells (HSPCs). In this study, we employed CsH for LV transduction of murine HSCs and defined haematopoietic progenitors, confirming previous findings in more specific subsets of primitive haematopoietic cells. Our data confirm increased efficiencies, in agreement with the published data. We further experimented with the transduction with the simultaneous use of several vectors. The use of CsH yielded an even more robust increase in rates of multi-vector infection than the increase for a single-vector. CsH was reported to reduce the innate resistance mechanism against LV infection. We indeed found that additional pretreatment could increase the efficiency of transduction, in agreement with the originally reported results. Our data also suggest that CsH does not reduce the efficiency of transplantation into immune-competent hosts or the differentiation of HSCs while enhancing stable long-term expression in vivo. This new additive will surely help many studies in animal models and might be very useful for the development of novel HSC gene therapy approaches.
CAPA neuropeptides and their receptor form an anti-diuretic hormone signaling system in the human disease vector, Aedes aegypti
Authors: Sajadi Farwa , Uyuklu Ali , Paputsis Christine , Lajevardi Aryan , Wahedi Azizia , Ber Lindsay Taylor , Matei Andreea , Paluzzi Jean-Paul V.
Published: February 2020

Insect CAPA neuropeptides are homologs of mammalian neuromedin U and are known to influence ion and water balance by regulating the activity of the Malpighian ‘renal’ tubules (MTs). Several diuretic hormones are known to increase primary fluid and ion secretion by insect MTs and, in adult female mosquitoes, a calcitonin-related peptide (DH31) called mosquito natriuretic peptide, increases sodium secretion to compensate for the excess salt load acquired during blood-feeding. An endogenous mosquito anti-diuretic hormone was recently described, having potent inhibitory activity against select diuretic hormones, including DH31. Herein, we functionally deorphanized, both in vitro and in vivo, a mosquito anti-diuretic hormone receptor (AedaeADHr) with expression analysis indicating highest enrichment in the MTs where it is localized within principal cells. Characterization using a heterologous in vitro system demonstrated the receptor was highly sensitive to mosquito CAPA neuropeptides while in vivo, AedaeADHr knockdown abolished CAPA-induced anti-diuretic control of DH31-stimulated MTs. CAPA neuropeptides are produced within a pair of neurosecretory cells in each of the abdominal ganglia, whose axonal projections innervate the abdominal neurohaemal organs, where these neurohormones are released into circulation. Lastly, pharmacological inhibition of nitric oxide synthase (NOS) and protein kinase G (PKG) signaling eliminated anti-diuretic activity of CAPA, highlighting the role of the second messenger cGMP and NOS/PKG in this anti-diuretic signaling pathway.
In utero elemental tags in vertebrae of the scalloped hammerhead shark Sphyrna lewini reveal migration patterns of pregnant females
Authors: Coiraton Claire , Amezcua Felipe
Published: February 2020

Vertebral microchemistry recently allowed to infer the migration patterns of the scalloped hammerhead shark Sphyrna lewini in the Mexican Pacific, however conclusions regarding the movements of reproductive females were hindered by the small sample size. Considering that S. lewini is a placental viviparous species, maternal supply of nutrients to the embryos might influence their vertebral microchemistry while in utero and provide intrinsic markers of the pregnant female environmental histories. This hypothesis was tested before attempting to infer the migration patterns of pregnant females through the analyses of the in utero elemental profiles quantified in the vertebrae of coastal young-of-the-year (‘YOY’). Vertebrae were obtained from sharks captured along the Mexican Pacific coast in 2016. Vertebral microchemistry was quantified using laser ablation inductively-coupled plasma mass spectrometry. Elemental signatures at vertebral edge were consistent between each pregnant female and her embryos demonstrating the viability of employing in utero elemental signatures as a maternal tag of the gestation-related environmental histories. Analyses of the YOY in utero Sr:Ba and Pb:Ca profiles suggested that pregnant females either (1) progressively migrated offshore before quickly returning to coastal habitats before term or (2) remained nearshore during complete gestation. Considering the endangered status of S. lewini, current management measures may be insufficient for the sustainable management of the population as pregnant females may be particularly susceptible to fisheries when remaining nearshore or entering coastal habitats prior to pupping.
Broadband microwave coding metamaterial absorbers
Authors: Tran Manh Cuong , Pham Van Hai , Ho Tuan Hung , Nguyen Thi Thuy , Do Hoang Tung , Bui Xuan Khuyen , Bui Son Tung , Le Dac Tuyen , Pham The Linh , Vu Dinh Lam
Published: February 2020

In this paper, a broadband metamaterial microwave absorber is designed, simulated and measured. Differently from the traditional method which is only based on unit cell boundary conditions, we carried out full-wave finite integration simulations using full-sized configurations. Starting from an elementary unit cell structure, four kinds of coding metamaterial blocks, 2 × 2, 3 × 3, 4 × 4 and 6 × 6 blocks were optimized and then used as building blocks (meta-block) for the construction of numerous 12 × 12 topologies with a realistic size scale. We found the broadband absorption response in the frequency range 16 GHz to 33 GHz, in good agreement with the equivalent medium theory prediction and experimental observation. Considering various applications of metamaterials or metamaterial absorbers in the electromagnetic wave processing, including the radars or satellite communications, requires the frequency in the range up to 40 GHz. Our study could be useful to guide experimental work. Furthermore, compared to the straightforward approach that represents the metamaterials configurations as 12 × 12 matrices of random binary bits (0 and 1), our new approach achieves significant gains in the broadband absorption. Our method also may be applied to the full-sized structures with arbitrary dimensions, and thus provide a useful tool in the design of metamaterials with specific desired frequency ranges.
Comparison of energy expenditure and substrate metabolism during overground and motorized treadmill running in Chinese middle-aged women
Authors: Li Shuo , Xue Jing-jing , Hong Ping , Song Chao , He Zi-hong
Published: February 2020

The purpose of this study was to compare differences of energy expenditure and substrate metabolism between motorized-treadmill and overground running in three different velocities in Chinese middle-aged women. In total, 74 healthy middle-aged women (age, 48 ± 4 years; height, 159.4 ± 4.9 cm; weight, 58.6 ± 6.7 kg; and body-mass index (BMI), 23.1 ± 2.7 kg/m2) volunteered to participate in this study. Bioelectrical-impedance analysis was used to measure body composition. Energy expenditure, carbohydrates (CHO), and fat oxidation were calculated with indirect calorimetry during motorized-treadmill and overground running. Running speed from slow to fast was 7.0, 8.0, and 9.0 km/h. The duration of each velocity was 6 min, separated by 5–15 min rest. There was no significant difference in energy expenditure between overground and treadmill running at the speed of 7 km/h (8.10 ± 1.25 vs. 7.75 ± 1.13 kcal/min, p > 0.05). Energy expenditure of overground running at 8 and 9 km/h was higher than that of treadmill running (9.36 ± 1.40 vs. 8.54 ± 1.21 kcal/min; 10.33 ± 1.55 vs. 9.54 ± 1.36 kcal/min; both p < 0.01). Fat contribution to energy consumption was significantly higher during treadmill running than during overground running (both p < 0.01) at speeds of 8 and 9 km/h. Overground running at high intensity incurred greater energy consumption than treadmill running did. However, results showed greater fat utilization during treadmill running than during overground running at high intensity. It is critical that these differences are taken into account when we prescribe training modes and intensities for middle-aged women.
ROR1 regulates chemoresistance in Breast Cancer via modulation of drug efflux pump ABCB1
Authors: Fultang Norman , Illendula Abhinav , Lin Jianhuang , Pandey Manoj K. , Klase Zachary , Peethambaran Bela
Published: February 2020

Chemoresistance is one of the leading causes of mortality in breast cancer (BC). Understanding the molecules regulating chemoresistance is critical in order to combat chemoresistant BC. Drug efflux pump ABCB1 is overexpressed in chemoresistant neoplasms where it effluxes various chemotherapeutic agents from cells. Because it is expressed in normal and cancerous cells alike, attempts at targeting ABCB1 directly have failed due to low specificity and disruption of normal tissue. A proposed method to inhibit ABCB1 is to target its cancer-specific, upstream regulators, mitigating damage to normal tissue. Few such cancer-specific upstream regulators have been described. Here we characterize ROR1 as an upstream regulator of ABCB1. ROR1 is highly expressed during development but not expressed in normal adult tissue. It is however highly expressed in several cancers. ROR1 is overexpressed in chemoresistant BC where it correlates with poor therapy response and tumor recurrence. Our data suggests, ROR1 inhibition sensitizes BC cells to chemo drugs. We also show ROR1 regulates ABCB1 stability and transcription via MAPK/ERK and p53. Validating our overall findings, inhibition of ROR1 directly correlated with decreased efflux of chemo-drugs from cells. Overall, our results highlight ROR1’s potential as a therapeutic target for multidrug resistant malignancies.
Process Intensification in Continuous Crystallization
Authors: Stelzer T. , Lakerveld R. , Myerson A. S.
Published: February 2020

Process intensification (PI) is a design approach that offers concrete benefits to improve the performance of processes and processing within many branches of the chemical, food, and pharmaceutical industry. Crystallization, an important unit operation within these industry branches, may also benefit from PI. Generally, the PI approaches can be categorized in four fundamental domains (time, space, function, energy). Continuous processing of crystallization is already by itself one of the PI approaches within the time domain. Although PI can also be achieved using batch crystallization concepts, this chapter will focus on PI approaches from all four domains beneficially applied in continuous crystallization settings. Each principle is illustrated with examples from academia and/or industry. Perspectives on the level of maturity of these examples and future PI challenges rounds out the chapter.
Process Analytical Technology in Continuous Crystallization
Authors: Simon L. L. , Simone E.
Published: February 2020

This chapter discusses the topic of process analytical technology (PAT) in the context of continuous manufacturing and crystallization. The chapter starts with the introduction of the quality by design (QbD) concept, which heavily relies on the application of PAT tools for its implementation. The next section discusses the most widely used PAT instruments for batch and continuous crystallization processes. Furthermore, the issues of data analysis and management for the application of PAT in continuous manufacturing and crystallization are discussed. A detailed discussion on the use of econometrics hypothesis tests for systematic steady-state detection is presented in one of paragraphs of this chapter. Model-free PAT-based control strategies for continuous crystallization processes are discussed in the second part of the chapter while the PAT implementation in the monitoring and control of mixed suspension mixed product removal (MSMPR) and tubular crystallizers are highlighted in the final two sections.
Continuous Enantioselective Crystallization of Chiral Compounds
Authors: Lorenz Heike , Temmel Erik , Seidel-Morgenstern Andreas
Published: February 2020

This chapter describes the possibility of attaining pure enantiomers through enantioselective crystallization. Focus is set on demonstrating options to realize separation processes operating continuously. Introductions are given to solid–liquid equilibria, the various types of phase diagrams of chiral systems, relevant kinetic phenomena, including metastable zones, and possible process options for batch and continuous separation of enantiomers. In the main part, results of case studies carried out in our laboratory are presented. Racemic mixtures of two conglomerates, namely D-/L-threonine and D-/L-asparagine monohydrate, were resolved by exploiting different variants of preferential crystallization, including two continuous operation modes.
Economic Analysis of Continuous Crystallisation
Authors: Diab Samir , Jolliffe Hikaru G. , Gerogiorgis Dimitrios I.
Published: February 2020

Continuous manufacturing can offer significant operating and economic benefits to both laboratory- and production scale campaigns, compared to currently dominant, yet expensive and inefficient, batch methods. Continuous crystallisation designs offer reduced batch-to-batch variation, but may attain lower yields than their batch counterparts if not optimised. Technoeconomic analyses of different crystallisation configurations are valid methodologies for rapid screening of cost-optimal designs to elucidate attainable benefits over traditional batch methods. Process modelling and optimisation can be implemented for rapid, comparative evaluation of multiple configurations to establish the most promising continuous crystallisation designs. Mixed suspension-mixed product removal (MSMPR) and continuous oscillatory baffled crystallisers (COBCs) are feasible and viable continuous crystalliser designs with a variety of experimental and modelling studies presented in the literature demonstrating their viability as a simple alternative to batch crystallisers. This work describes the technoeconomic evaluation and optimisation of different crystallisation configurations for three active pharmaceutical ingredients (APIs): cyclosporine, paracetamol and aliskiren. Total cost minima are compared for different design scenarios (recycle consideration, number of implemented crystallisers, specified plant capacity) to elucidate cost-optimal designs. The current work highlights the effect of a variety of process considerations for crystalliser design and the importance of technoeconomic optimisation at the early stages of continuous crystallisation process development.
Digital Design and Operation of Continuous Crystallization Processes via Mechanistic Modelling Tools
Authors: Mitchell Niall A. , Bermingham Sean K. , Burcham Christopher L. , Polster Christopher S. , Tahir Furqan , Mack John
Published: February 2020

This chapter will outline the application of digital design tools, specifically mechanistic models in the pharmaceutical industry, to enable more efficient development, design and control of API crystallization processes. Calibrated mechanistic models for crystallization can facilitate a more efficient workflow for studying and designing new continuous crystallization process, by characterising the process kinetics using batch crystallization data. The calibrated crystallization kinetics can then be utilised to inform the configuration of the continuous crystallization process, such as the number of stages to employ and the set-points for each stage. This analysis can be performed in silico via simulation prior to performing any continuous crystallization runs. It was shown in the first case study that the mechanistic model of the continuous crystallization can subsequently be employed to optimise the process to desired objective functions and provide a means to understand the various processing trade-offs. Finally, it was also shown how these mechanistic models can be further applied to facilitate the more efficient development of online MPCs. In comparison to the data-driven approach, the mechanistic models have the potential to significantly reduce the experimental effort, as well as material usage for MPC development.
Highly sensitive fluorescent carbon dots probe with ratiometric emission for the determination of ClO−
Authors: Zhang Huilin , Gao Yifang , Jiao Yuan , Lu Wenjing , Shuang Shaomin , Dong Chuan
Published: February 2020

A ratiometric fluorescent N,S co-doped carbon dots (N,S-CD) probe for ClO− has been facilely obtained via a one-step hydrothermal method.
Construction of trifluoromethylated quaternary stereocenters via p-quinone methides
Authors: Terashima Kyu , Kawasaki-Takasuka Tomoko , Agou Tomohiro , Kubota Toshio , Yamazaki Takashi
Published: February 2020

Development of a new synthetic method for the construction of quaternary centers with a CF3 group was realized by way of 1,6-addition of various nucleophiles to highly reactive δ-trifluoromethylated p-quinone methides generated in situ.
Building a smart surface with converse temperature-dependent wettability based on poly(acrylamide-co-acrylonitrile)
Authors: Chen Longbin , Yang Tao , Niu Yue , Mu Xin , Gong Yelei , Feng Yancong , de Rooij Nicolaas Frans , Wang Yao , Li Hao , Zhou Guofu
Published: February 2020

A sensitive, adjustable, and reversible smart surface with converse temperature-dependent wettability was constructed from an upper critical solution temperature-type copolymer.
Effects of electrospray mechanisms and structural relaxation on polylactide ion conformations in the gas phase: insights from ion mobility spectrometry and molecular dynamics simulations
Authors: Duez Quentin , Metwally Haidy , Hoyas Sébastien , Lemaur Vincent , Cornil Jérôme , De Winter Julien , Konermann Lars , Gerbaux Pascal
Published: February 2020

Gas-phase polymer ions may retain structural features associated with their electrospray formation mechanisms.
Unravelling the configuration of transient ortho-quinone methides by combining microfluidics with gas phase vibrational spectroscopy
Authors: Mayer Martin , Pahl Maik , Spanka Matthias , Grellmann Max , Sickert Marcel , Schneider Christoph , Asmis Knut R. , Belder Detlev
Published: February 2020

The alkylidene double bond configuration of transient ortho-quinone methides (o-QMs) is studied by cryogenic ion trap vibrational spectroscopy.
Confined benzene within InOF-1: contrasting CO2and SO2capture behaviours
Authors: Barrios-Vargas Luz J. , Ruiz-Montoya José G. , Landeros-Rivera Bruno , Álvarez J. Raziel , Alvarado-Alvarado Daniel , Vargas Rubicelia , Martínez Ana , González-Zamora Eduardo , Cáceres Ludy M. , Morales Juan C. , Ibarra Ilich A.
Published: February 2020

Benzene confinement enhances the CO2capture while decreases the SO2capture within InOF-1 due to the competition among molecules for the preferential adsorption sites. Pore channel view ofCO2Bz@InOF-1b(left) andSO2⋯Bz@InOF-1b(right) systems.
Electrochromic behaviour of Ir(iii) bis-cyclometalated 1,2-dioxolene tetra-halo complexes: fully reversible catecholate/semiquinone redox switches
Authors: Liguori Paola Francesca , Ghedini Mauro , La Deda Massimo , Godbert Nicolas , Parisi Francesco , Guzzi Rita , Ionescu Andreea , Aiello Iolinda
Published: February 2020

Ir(iii) redox switchable cyclometallated complexes were synthesized and their paramagnetic and electrochromic properties were investigated.
Dinuclear acetylide-bridged ruthenium(ii) complexes with rigid non-aromatic spacers
Authors: Naik Surabhi , Scottwell Synøve Ø. , Li Hsiu L. , Leong Chanel F. , D'Alessandro Deanna M. , Field Leslie D.
Published: February 2020

A series of dinuclear acetylide-bridged ruthenium complexes with rigid linkers 1,4-bicyclooctane and 1,12-p-carborane was synthesised and the metal-to-metal communication through the bridge was explored using cyclic voltammetry.
Bimetal composites for photocatalytic reduction of CO2 to CO in the near-infrared region by the SPR effect
Authors: Jiang Hua , Gong Shuaiqi , Xu Shu , Shi Penghui , Fan Jinchen , Cecen Volkan , Xu QunJie , Min YuLin
Published: February 2020

A major challenge in the field of photocatalytic carbon dioxide (CO2) reduction is to design catalyst systems featuring high selectivity for CO production, long-term stability and a composition of Earth-abundant elements.
Simultaneous sensitive detection and rapid adsorption of UO22+ based on a post-modified sp2 carbon-conjugated covalent organic framework
Authors: Zhang Cheng-Rong , Cui Wei-Rong , Jiang Wei , Li Fang-Fang , Wu Yi-Di , Liang Ru-Ping , Qiu Jian-Ding
Published: February 2020

Design of synthesis of regenerable fluorescent sp2 carbon-conjugated covalent organic frameworks for selective detection and extraction of uranium.
Branched-chain amino acids, especially of leucine and valine, mediate the protein restricted response in a piglet model
Authors: Yin Jie , Ma Jie , Li Yuying , Ma Xiaokang , Chen Jiashun , Zhang Haihan , Wu Xin , Li Fengna , Liu Zhiqiang , Li Tiejun , Yin Yulong
Published: February 2020

Branched-chain amino acids (BCAAs) are reduced in various protein restricted models, while the detailed role of BCAAs in protein restricted response is still obscure.
OPENchip: an on-chip in situ molecular profiling platform for gene expression analysis and oncogenic mutation detection in single circulating tumour cells
Authors: Lee Amos C. , Svedlund Jessica , Darai Evangelia , Lee Yongju , Lee Daewon , Lee Han-Byoel , Kim Sung-Min , Kim Okju , Bae Hyung Jong , Choi Ahyoun , Lee Sumin , Jeong Yunjin , Song Seo Woo , Choi Yeongjae , Yeom Huiran , Lee Caleb S. , Han Wonshik , Lee Dong Soon , Jang Jin-Young , Madaboosi Narayanan , Nilsson Mats , Kwon Sunghoon
Published: February 2020

On-chip in situ molecular profiling for gene expression analysis and oncogenic mutation detection in single circulating tumour cells is presented.
Beyond graphene oxide: laser engineering functionalized graphene for flexible electronics
Authors: Rodriguez Raul D. , Khalelov Alimzhan , Postnikov Pavel S. , Lipovka Anna , Dorozhko Elena , Amin Ihsan , Murastov Gennadiy V. , Chen Jin-Ju , Sheng Wenbo , Trusova Marina E. , Chehimi Mohamed M. , Sheremet Evgeniya
Published: February 2020

We show a novel concept for the design of graphene-based materials via diazonium-mediated functionalization and subsequent laser treatment for flexible electronics.
Construction of efficient dual activating ratiometric YVO4:Nd3+/Eu3+ nanothermometers using co-doped and mixed phosphors
Authors: Kolesnikov Ilya E. , Mamonova Daria V. , Kalinichev Alexey A. , Kurochkin Mikhail A. , Medvedev Vasiliy A. , Kolesnikov Evgenii Yu. , Lähderanta Erkki , Manshina Alina A.
Published: February 2020

Co-doped and mixed nanoparticles were used for the construction of highly sensitive dual activating ratiometric luminescent thermometers and their performances were compared.
Continuous ultrathin UiO-66-NH2 coatings on a polymeric substrate synthesized by a layer-by-layer method: a kind of promising membrane for oil–water separation
Authors: Gao Jian , Wei Wei , Yin Yuan , Liu Meihua , Zheng Chunbai , Zhang Yifan , Deng Pengyang
Published: February 2020

An ultrathin UiO-66-NH2 coating based on a polymeric substrate was prepared by a layer-by-layer method and exhibited good oil–water separation performance.
How does cross-conjugation influence thiol additions to enones? A computational study of thiol trapping by the naturally occurring divinyl ketones zerumbone and α-santonin
Authors: Ting Jonathan Y. C. , Roseli Ras Baizureen , Krenske Elizabeth H.
Published: February 2020

DFT calculations show how the kinetics and thermodynamics of thiol additions to enones are affected by incorporation of the enone into a cross-conjugated divinyl ketone moiety.
Organocatalytic C–H fluoroalkylation of commodity polymers
Authors: Lewis Sally E. , Wilhelmy Bradley E. , Leibfarth Frank A.
Published: February 2020

Organocatalytic post-polymerization modification of commodity aromatic polymers diversifies their material properties.
High temperature Fe(iii) spin crossover behaviours in three unprecedented FeIII–MII–FeIII(M = Fe, Cd) linear trinuclear complexes
Authors: Ouyang Zhi-Jian , Mo Xiao-Ying , Yang Meng , Zhong Li , Chen Wen-Bin , Gao Song , Dong Wen
Published: February 2020

An azo-based ligand of azotetrazolyl-2,7-dihydroxynaphthalene (H3ATD) was used to synthesize three FeIII–MII–FeIII(M = Fe, Cd) linear trinuclear complexes with different high temperature spin crossover (SCO) behaviours for the terminal FeIIIions.
Cocrystallization with a clip-type molecule catcher: a new method to determine structures of liquid molecules
Authors: Liu Yuezhou , Chen Panpan , Shi Bingbing , Jiao Tianyu , Ju Huaqiang , Liu Peiren , Huang Feihe
Published: February 2020

In order to measure the precise structure of liquid molecules by X-ray single-crystal diffraction, we report a new and easy method using a glycoluril-derived molecular clip as a molecule catcher to form cocrystals with liquid molecules.
Discovery of highly functionalized 5,6-seco-grayanane diterpenoids as potent competitive PTP1B inhibitors
Authors: Zhou Junfei , Zuo Zhili , Liu Junjun , Zhang Hanqi , Zheng Guijuan , Yao Guangmin
Published: February 2020

Three competitive PTP1B inhibitory diterpenoids with a 5,6-seco-grayanane carbon skeleton (1–3) were isolated and identified fromRhododendron molle. A more potent competitive PTP1B inhibitor (9) was designed and prepared based on a docking study.
Synthesis, intermolecular interactions and biological activities of two new organic–inorganic hybrids C6H10N2,2Br and C6H10N2,2Cl·H2O
Authors: Hamdi Intissar , Bkhairia Intidhar , Roodt Andreas , Roisnel Thierry , Nasri Moncef , Naïli Houcine
Published: February 2020

A slow evaporation method has permitted the crystallization of two novel crystals of (2-aminomethyl)pyridindiumdihalide C6H10N2,2Br (1) and C6H10N2,2Cl·H2O (2).