bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing theory from practice: A case study in civil engineering airport design problem‐based learning
Authors: Pasandín Ana M. R. , Pérez Ignacio P.
Published: November 2020

In Spain, the students of the Master of Sciences (MSc) level in Civil Engineering have competencies in airport design, construction, conservation, and exploitation. Considering the need for improving the knowledge of these students in this area, the School of Civil Engineering of A Coruña implemented in the subject of Infrastructure of Roads and Airports (ICA) a brief workshop on airport design. This paper presents a case study in which problem‐based learning techniques were applied in this airport design workshop. To promote the students' interaction and improve their social skills, the workshop activities were conducted as onsite tasks. The workshop starting point was an individual real case of airport runway design. Master classes, practical lessons, private tutoring, specific software, audio‐visual material, and supporting documentation posted on the ICA Moodle site were used as teaching and learning resources. In particular, an analysis of the basic International Civil Aviation Organization standards on airport design was used by the students to solve their problem. In addition, for the design of the runway orientation, the ICA students used both the Federal Aviation Administration's WindRose computer online application and the traditional manual method. The results of both methods were critically compared. The high level of satisfaction indicated by the survey conducted at the end of the subject indicated the success of this teaching and learning methodology.
The experience of living with very high empathy: A critical realist, pragmatic approach to exploring objective and subjective layers of the phenomenon
Authors: Leonard Sally Rachel Kate , Willig Carla
Published: November 2020

Aims/objectives

Combining mixed methods in a pragmatic way, this research attempts to address the research question without being limited by methods’ philosophical and methodological constraints, which have traditionally separated quantitative and qualitative research. High empathy (HE) has been largely unexamined, considered an adaptive female skill facilitating interpersonal relationships. This research aims to contribute to the gap in research regarding the lived experience of HE.

Methodology/method

Within the critical realist paradigm, the Empathy Quotient (EQ) was used online to select the first eight participants who scored over 70/80 (average male score = 41/80, average female = 47/80). They were invited to a 90‐min interview, transcribed verbatim and analysed using interpretative phenomenological analysis (Smith, Flowers, & Larkin, 2009). Participants were women aged 25 to 68 years.

Results/findings

Using the EQ followed by IPA, we were able to significantly contribute to the existing research and theory, for example empathising‐systemising theory, mirror‐sensory synaesthesia, emotional intelligence, social intelligence, compassion fatigue, burnout, pathological altruism and compulsive caregiving syndrome.

Discussion/conclusions

HE is not simply an adaptive and socially beneficial skill as previously thought, nor is it pathological in itself. HE presented as significantly impacting intrapersonal and interpersonal processes sometimes for benefit within both the professional and personal realms but often with negative impact. Healthy management consists of clear boundaries between self/other and mature skills of emotional regulation lessening empathic distress (Pathological Altruism, 2012) allowing for empathic concern and feelings of emotional self‐esteem, in what participants termed ‘empathic wisdom’.
Nonprofit organization advertising on social media: The role of personality, advertising appeals, and bandwagon effects
Authors: Lim Hayoung Sally , Bouchacourt Lindsay , Brown‐Devlin Natalie
Published: November 2020

The current study aims to explore the role of personality in a nonprofit organization's advertisement on social media and how it influences two advertising components: the types of advertising appeal and social media metrics. A 2 (emotional vs. rational appeal) × 2 (high vs. low social media metrics) full‐factorial experiment was conducted. We found the positive effects of specific personality traits on attitude toward the ad and donation intention; the six HEXACO personality traits were positively related to attitude toward the ad, whereas Extraversion, Conscientiousness, and Openness to experience were the only traits positively related to donation intention. There was no interaction effect of the personality traits and the type of advertising appeal. We also found that Conscientiousness had a moderating role on the bandwagon effect of social media metrics, such that the bandwagon effects of social media metrics on the attitude toward the ad and donation intentions were only significant for participants with moderate (M) Conscientiousness and high (M + 1SD) Conscientiousness. Our findings will contribute to providing practical insights for how to design an effective nonprofit advertisement on social media as well as filling the gap in the literature on nonprofit advertising and personality.
Efficient and Short Method for Conjugation of 1‐Nitro‐9‐Aminoacridine to Important Peptidyl Fragments by a Solid Support Synthesis
Authors: Lahutta Monika
Published: November 2020

The efficient and short techniques for conjugation of 9‐aminoacridine with different peptidyl fragments are necessary for the development of active pharmaceutical ingredients (API). They need to be adopted to generate a new branch of acridine conjugates, enhancing their bioavailability for the examination in biological systems. The branch of developing acridine conjugates, built via different linkers and synthesized in this study, are expected as potential effective chemotherapeutics with dual mechanism of action. Recently, the methodology based on a solid‐phase technique has been successfully demonstrated in preparing a number of promising compounds. However, the reaction conditions for amide bond formation between 1‐nitro‐9‐aminoacridine and peptidyl fragments need to be optimized. In this study, the optimization of amide bond formation was demonstrated with the use of the solid‐phase synthesis to build a new promising group of 1‐nitro‐9‐aminoacridines conjugated to lactoferrin fragments via especially carboxy linker length.
Diterpenoids from the Whole Plants of Ajuga nipponensis and Their Inhibition of RANKL‐Induced Osteoclastogenesis
Authors: Wang Haijuan , Teng Xifeng , Zhang Yuting , Gu Qiong , He Lin
Published: November 2020

Two new diterpenoids, ajudecunoid A (1) and ajudecunoid B (14), along with thirteen known diterpenoids, were isolated from the whole plants of Ajuga nipponensis Makino. Their structures were elucidated by the extensive spectroscopic analysis (UV, IR, MS, and NMR). The absolute configurations of ajudecunoid A (1) and ajudecunoid B (14) were defined through analysis of X‐ray crystallography. Fifteen compounds were evaluated for inhibition of the formation of osteoclasts in bone marrow‐derived macrophages (BMM) cells. Two neo‐clerodane diterpenoids ajuganipponin B (5) and (12S)‐6α,19‐diacetoxy‐18‐chloro‐4α‐hydroxy‐12‐tigloyloxy‐neo‐clerod‐13‐en‐15,16‐olide (12) showed significant inhibition of osteoclastogenesis with IC50 values of 0.88 and 0.79 μM, respectively. Here we firstly reported diterpenoids with anti‐osteoclastogenesis activity from A. nipponensis.
Chemical Translational Biology: Redefining Druggability of Protein‐Protein Interactions
Authors: Cesa Laura C.
Published: November 2020

Chemical biologists use chemical tools to answer biological questions. The translational application of these principles has led to an explosion in the discovery and druggability of new protein targets, including protein‐protein interactions (PPIs). Proteins tend to interact with other macromolecules using relatively large and featureless binding surfaces, which has hampered traditional drug discovery efforts, particularly for interactions with weaker affinity. In this article, I discuss several emerging strategies for targeting PPIs, including computational and structural methods and novel screening approaches. In particular, I focus on hijacking intrinsic protein allosteric pathways for the discovery and design of small‐molecule and peptide ligands.
Site‐Specific Antibody Fragment Conjugates for Reversible Staining in Fluorescence Microscopy
Authors: Schwach Jonathan , Kolobynina Ksenia , Brandstetter Katharina , Gerlach Marcus , Ochtrop Philipp , Helma Jonas , Hackenberger Christian P. R. , Harz Hartmann , Cardoso M. Cristina , Leonhardt Heinrich , Stengl Andreas
Published: November 2020

Antibody conjugates have taken a great leap forward as tools in basic and applied molecular life sciences that was enabled by the development of chemoselective reactions for the site‐specific modification of proteins. Antibody‐oligonucleotide conjugates combine the antibody's target specificity with the reversible, sequence‐encoded binding properties of oligonucleotides like DNAs or peptide nucleic acids (PNAs), allowing sequential imaging of large numbers of targets in a single specimen. In this report, we use the Tub‐tag® technology in combination with Cu‐catalyzed azide‐alkyne cycloaddition for the site‐specific conjugation of single DNA and PNA strands to an eGFP‐binding nanobody. We show binding of the conjugate to recombinant eGFP and subsequent sequence‐specific annealing of fluorescently labelled imager strands. Furthermore, we reversibly stain eGFP‐tagged proteins in human cells, thus demonstrating the suitability of our conjugation strategy to generate antibody‐oligonucleotides for reversible immunofluorescence imaging.
Development of the First Potential Nonpeptidic Positron Emission Tomography Tracer for the Imaging of CCR2 Receptors
Authors: Wagner Stefan , de Moura Gatti Fernando , Silva Daniel G. , Ortiz Zacarias Natalia V. , Zweemer Annelien J. M. , Hermann Sven , De Maria Monica , Koch Michael , Weiss Christina , Schepmann Dirk , Heitman Laura H. , Tschammer Nuska , Kopka Klaus , Junker Anna
Published: November 2020

Herein we report the design and synthesis of a series of highly selective CCR2 antagonists as 18F‐labeled PET tracers. The derivatives were evaluated extensively for their off‐target profile at 48 different targets. The most potent and selective candidate was applied in vivo in a biodistribution study, demonstrating a promising profile for further preclinical development. This compound represents the first potential nonpeptidic PET tracer for the imaging of CCR2 receptors.
Defining the role of neoadjuvant systemic therapy in high‐risk retroperitoneal sarcoma: A multi‐institutional study from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group
Authors: Tseng William W. , Barretta Francesco , Conti Lorenzo , Grignani Giovanni , Tolomeo Francesco , Albertsmeier Markus , Angele Martin K. , Rutkowski Piotr , Skoczylas Jacek , De Paoli Antonino , Navarria Federico , Raut Chandrajit P. , Fairweather Mark , Farma Jeffrey M. , Nessim Carolyn , Goel Neha , Grignol Valerie P. , Ford Samuel J. , Cardona Kenneth , Subhawong Ty , Tattersall Hannah L. , Lee Rachel M. , Hu James S. , von Mehren Margaret , Sanfilippo Roberta , Gronchi Alessandro
Published: November 2020

Background

In patients with retroperitoneal sarcoma (RPS), the incidence of recurrence after surgery remains high. Novel treatment approaches are needed. This retrospective study evaluated patients with primary, high‐risk RPS who received neoadjuvant systemic therapy followed by surgery to 1) determine the frequency and potential predictors of radiologic tumor responses and 2) assess clinical outcomes.

Methods

Clinicopathologic data were collected for eligible patients treated at 13 sarcoma referral centers from 2008 to 2018. Univariable and multivariable logistic models were performed to assess the association between clinical predictors and response. Overall survival (OS) and crude cumulative incidences of local recurrence and distant metastasis were compared.

Results

Data on 158 patients were analyzed. A median of 3 cycles of neoadjuvant systemic therapy (interquartile range, 2‐4 cycles) were given. The regimens were mostly anthracycline based; however, there was significant heterogeneity. No patients demonstrated a complete response, 37 (23%) demonstrated a partial response (PR), 88 (56%) demonstrated stable disease, and 33 (21%) demonstrated progressive disease (PD) according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Only a higher number of cycles given was positively associated with PR (P = .005). All patients underwent complete resection, regardless of the tumor response. Overall, patients whose tumors demonstrated PD before surgery showed markedly worse OS (P = .005). An indication of a better clinical outcome was seen in specific regimens given for grade 3 dedifferentiated liposarcoma and leiomyosarcoma.

Conclusions

In patients with high‐risk RPS, the response to neoadjuvant systemic therapy is fair overall. Disease progression on therapy may be used to predict survival after surgery. Subtype‐specific regimens should be further validated.
Population Pharmacokinetic Model for Ertugliflozin in Healthy Subjects and Patients With Type 2 Diabetes Mellitus
Authors: Fediuk Daryl J. , Zhou Susan , Dawra Vikas Kumar , Sahasrabudhe Vaishali , Sweeney Kevin
Published: November 2020

Ertugliflozin is a selective sodium‐glucose cotransporter 2 inhibitor approved as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (T2DM). A population pharmacokinetic (popPK) model was developed to characterize the pharmacokinetics (PK) of ertugliflozin and quantify the influence of intrinsic (eg, body weight, age, sex, race, estimated glomerular filtration rate [eGFR], T2DM) and extrinsic (eg, food) covariates on the PK parameters of ertugliflozin. The analysis was conducted using data from 15 clinical studies (phases 1‐3) enrolling healthy subjects and patients with T2DM, which included 13,691 PK observations from 2276 subjects and was performed using nonlinear mixed‐effects modeling. A 2‐compartment popPK model with first‐order absorption and a lag time and first‐order elimination, described the plasma concentration–time profile of ertugliflozin after single and multiple dosing in healthy subjects and in patients with T2DM. Apparent clearance increased with increasing body weight and eGFR, was slightly lower in patients with T2DM and females, and was slightly higher in Asians. Apparent central volume of distribution increased with increasing body weight and was higher in females and Asians. Administration of ertugliflozin with food decreased the absorption rate constant (ka) and relative bioavailability (F1) compared with fasted. When ertugliflozin was administered without regard to food, estimates of ka and F1 were similar to those for administration with food. The popPK model successfully characterized ertugliflozin exposure in healthy subjects and patients with T2DM. None of the covariates evaluated had a clinically relevant effect on ertugliflozin PK.
Supramolecular Ladder Assemblies as a Model for Probing Electronic Interactions between Multiple Stacked π‐Conjugated Systems
Authors: Huang Chi‐Huao , Jardel Damien , Lautrette Guillaume , Pianet Isabelle , Kuhn Alexander , Bassani Dario M.
Published: November 2020

A series of mono‐, di‐, and tri‐topic receptors in which H‐bonding sites, complementary to those of barbituric acid (BA), are fused is used to induce the supramolecular assembly of n×m ladders containing 1, 2, or 3 triphenylenevinylene units appended with BA. The topological constraint enforced by the architectures induces through‐space interactions between the electroactive moieties that are reflected in the electronic absorption and emission spectrum. The n=2, m=2 or m=3 architectures undergo two single electron oxidation events, indicative of the formation of the corresponding mono‐ and di‐radical cation species with comproportionation constants of 340 and 70, respectively. Comparison of the electrochemical potentials suggests that the charges are delocalized over the electroactive units in the assembly.
Genotyping validates the efficacy of photographic identification in a capture‐mark‐recapture study based on the head scale patterns of the prairie lizard (Sceloporus consobrinus)
Authors: Tomke Sarah A. , Kellner Chris J.
Published: November 2020

Population studies often incorporate capture‐mark‐recapture (CMR) techniques to gather information on long‐term biological and demographic characteristics. A fundamental requirement for CMR studies is that an individual must be uniquely and permanently marked to ensure reliable reidentification throughout its lifespan. Photographic identification involving automated photographic identification software has become a popular and efficient noninvasive method for identifying individuals based on natural markings. However, few studies have (a) robustly assessed the performance of automated programs by using a double‐marking system or (b) determined their efficacy for long‐term studies by incorporating multi‐year data. Here, we evaluated the performance of the program Interactive Individual Identification System (I3S) by cross‐validating photographic identifications based on the head scale pattern of the prairie lizard (Sceloporus consobrinus) with individual microsatellite genotyping (N = 863). Further, we assessed the efficacy of the program to identify individuals over time by comparing error rates between within‐year and between‐year recaptures. Recaptured lizards were correctly identified by I3S in 94.1% of cases. We estimated a false rejection rate (FRR) of 5.9% and a false acceptance rate (FAR) of 0%. By using I3S, we correctly identified 97.8% of within‐year recaptures (FRR = 2.2%; FAR = 0%) and 91.1% of between‐year recaptures (FRR = 8.9%; FAR = 0%). Misidentifications were primarily due to poor photograph quality (N = 4). However, two misidentifications were caused by indistinct scale configuration due to scale damage (N = 1) and ontogenetic changes in head scalation between capture events (N = 1). We conclude that automated photographic identification based on head scale patterns is a reliable and accurate method for identifying individuals over time. Because many lizard or reptilian species possess variable head squamation, this method has potential for successful application in many species.
Performance Assessment of Spectrum Selective Nanofluid‐Based Cooling for a Self‐Sustaining Greenhouse
Authors: Sajid Muhammad Usman , Bicer Yusuf
Published: November 2020

In hot climatic conditions, the temperature inside a greenhouse is much higher than the ambient temperature and requires significant cooling to maintain the temperature in the optimal range. This study proposes a novel concept for a self‐sustaining greenhouse, which integrates evacuated tube collectors, a multistage flash desalination system, vapor absorption cooling system, and photovoltaic thermal (PV/T) system to produce freshwater, cooling, and electricity. The PV/T system uses spectrum selective nanofluid that is circulated over the roof of the greenhouse and absorbs solar radiation having wavelengths greater than 1400 nm to reduce cooling load inside the greenhouse and optimize the spectrum use. The performance of the proposed system is evaluated using energy and exergy analysis. The energy efficiencies of the evacuated tube collector, desalination unit, and PV/T system are obtained as 45.85%, 46.16%, and 51.25%, respectively. The absorption cooling system achieves an energetic coefficient of performance of 0.83. The overall energy and exergy efficiencies of the proposed system are found to be 30% and 5.88%, respectively. The application of spectrum selective nanofluid on the roof of the greenhouse yields about 26% reduction in the cooling load of the greenhouse.
Seismic evaluation of two‐elevation ceiling system by shake table tests
Authors: Qi Liangjie , Kurata Masahiro , Ikeda Yoshiki , Kunitomo Keiichiro , Takaoka Masashi
Published: November 2020

Past earthquakes highlighted the vulnerability of the suspended ceiling, especially in earthquake‐prone countries like Japan; the post‐earthquake reconnaissance showed that damage to ceiling systems led to immeasurable economic loss and disturbance of the timely rescue of casualty. The existing studies have mostly focused on the seismic performance of regular square and leveled ceilings, whereas the inevitable requirements to accommodate air ducts, nonstructural piping, and electrical equipment resulted in a two‐elevation ceiling system. This paper reports a series of full‐scale shake table tests on a typical two‐elevation ceiling system, which includes electrical equipment, piping system, and commonly used suspended ceiling structure. Experimental observations showed that the two‐elevation ceiling system performed well under earthquake excitation. No fallen panels or overall system collapse occurred during shaking. This paper discusses the effects of a temporary‐positioning‐bracing bar (TPBB) between two ceiling elevations and peripheral constraints by surrounding wall on the acceleration and displacement response and torsional behavior in the ceiling system. Then, a simplified analytical model was established and verified with the experimental response of different ceiling configurations. The test results indicated that a sufficiently strong TPBB is essential to reduce the relative displacement between two ceiling elevations, and it ensures the integrity of two ceiling elevations in the ceiling system. In conclusion, the TPBB shall remain in the ceiling system after the construction stage.
Could N‐acetylcysteine improve the safety of clozapine?
Authors: Chrétien Basile , Fedrizzi Sophie , Lelong‐Boulouard Véronique , Sassier Marion , Alexandre Joachim , Dolladille Charles
Published: November 2020

Clozapine is an atypical antipsychotic indicated in patients with treatment‐resistant schizophrenia which remains underused due to safety issues. Mechanisms behind these adverse effects are complex and not fully understood. They may involve immune‐related mechanisms, direct toxic effects and oxidative stress. Clozapine‐induced oxidative stress might indeed notably be involved in the onset of neutropenia, agranulocytosis, myocarditis, sialorrhea, and metabolic alterations. Therefore, the association of N‐acetylcysteine (NAC), an easily accessible, low‐cost and well tolerated antioxidant drug could be of interest in clozapine‐treated patients to improve clozapine safety. Furthermore, according to recent studies NAC could help to improve schizophrenia symptoms. We believe that the use of NAC in the context of clozapine prescribing merits further study, as it could improve clozapine safety which may lead to a wider use and ultimately improve the healthcare of thousands of patients. NAC could also secondarily show positive knock‐on effects for the patients by improving clinical symptoms of schizophrenia in synergy with clozapine, and by reducing substance abuse and thus by improving the patient's overall condition. However, given the rarity of clozapine‐induced severe adverse effects, only a large volume of data (e.g., National adverse events monitoring) could assess the benefits of NAC on clozapine safety.
Linking hydrological variations at local scales to regional climate teleconnection patterns
Authors: Rasouli Kabir , Scharold Karis , Mahmood Taufique H. , Glenn Nancy F. , Marks Danny
Published: November 2020

Climate patterns over preceding years affect seasonal water and moisture conditions. The linkage between regional climate and local hydrology is challenging due to scale differences, both spatially and temporally. In this study, variance, correlation, and singular spectrum analyses were conducted to identify multiple hydroclimatic phases during which climate teleconnection patterns were related to hydrology of a small headwater basin in Idaho, USA. Combined field observations and simulations from a physically based hydrological model were used for this purpose. Results showed statistically significant relations between climate teleconnection patterns and hydrological fluxes in the basin, and climate indices explained up to 58% of hydrological variations. Antarctic Oscillation (AAO), North Atlantic Oscillation (NAO), and Pacific North America (PNA) patterns affected mountain hydrology, in that order, by decreasing annual runoff and rain on snow (ROS) runoff by 43% and 26% during a positive phase of NAO and 25% and 9% during a positive phase of PNA. AAO showed a significant association with the rainfall‐to‐precipitation ratio and explained 49% of its interannual variation. The runoff response was affected by the phase of climate variability indices and the legacy of past atmospheric conditions. Specifically, a switch in the phase of the teleconnection patterns of NAO and PNA caused a transition from wet to dry conditions in the basin. Positive AAO showed no relation with peak snow water equivalent and ROS runoff in the same year, but AAO in the preceding year explained 24 and 25% (p < 0.05) of their variations, suggesting that the past atmospheric patterns are equally important as the present conditions in affecting local hydrology. Areas sheltered from the wind and acted as a source for snow transport showed the lowest (40% below normal) ROS runoff generation, which was associated with positive NAO that explained 33% (p < 0.01) of its variation. The findings of this research highlighted the importance of hydroclimatic phases and multiple year variations that must be considered in hydrological forecasts, climate projections, and water resources planning.
Determinants of the renminbi anchor effect: From the perspective of the belt and road initiative
Authors: Cai Wanlin
Published: November 2020

The scope of this study is to empirically test the renminbi's (RMB) anchor effect. Since the proposal of the Belt and Road (B&R) Initiative, the RMB is shown to have made more remarkable progress as an anchor currency in B&R countries compared to non‐B&R countries. The ordered logit model is then used to examine the determinants of the RMB anchor effect. The results show that the probability of the RMB being an anchor currency increases with the higher the trade integration, the higher the investment dependence, the better the RMB infrastructure and the closer the policy cooperation. The results also provide evidence on how to further strengthen the RMB anchor effect and promote the RMB internationalization in the long run. On the basis of strengthening its policy cooperation with B&R countries, China should use its sustainable growth of trade and investment to provide the impetus for RMB internationalization. Furthermore, it should optimize the layout of the RMB offshore market, increase the openness of the financial market, and strengthen currency cooperation among central banks to provide guarantees for RMB internationalization.
Cadmium exposure induces endothelial dysfunction via disturbing lipid metabolism in human microvascular endothelial cells
Authors: Liang Hao , Yue Rongchuan , Zhou Chao , Liu Mengyu , Yu Xi , Lu Shengzhong , Zeng Jing , Yu Zhengping , Zhou Zhou , Hu Houxiang
Published: November 2020

Cadmium (Cd) is an occupational and environmental heavy metal pollutant derived from many sources that is linked to endothelial homeostasis. The endothelium is an important site of Cd deposition, while increasing evidence has revealed there is a close relationship between endothelial dysfunction and abnormal lipid metabolism. However, the effects of the alterations in lipid metabolism on endothelial cells (ECs) after Cd exposure still remain unclear. In our study, human microvascular endothelial cells (HMEC‐1) were exposed to 40‐μM Cd for 6, 12, or 24 h or 10‐, 20‐, or 40‐μM Cd for 24 h, respectively. The Cd exposure accelerated the decomposition of triglyceride (TG) and resulted in the accumulation of free fatty acids (FFAs). These changes stimulated cytotoxicity, impaired fatty acid oxidation (FAO), induced reactive oxygen species (ROS) generation, altered the mitochondrial membrane potential (MMP), and decreased the ATP content, which eventually led to endothelial dysfunction and cell death. In summary, exposure to cadmium caused endothelial dysfunction by disrupting lipid metabolism in HMEC‐1. These changes were mainly due to FFA accumulation and FAO inhibition, which further induced ROS generation and mitochondrial dysfunction. Moreover, our results provide novel insight into understanding the alterations of lipid metabolism induced by Cd exposure in ECs.
Near‐infrared double‐illumination optical‐resolution photoacoustic microscopy
Authors: Li Mingsheng , Shi Jiawei , Yiu Canice Chun‐Yin , Li Can , Wong Kenneth Kin‐Yip , Wang Lidai
Published: November 2020

Label‐free chemical bond imaging is of great importance in biology and medicine. Photoacoustic imaging at the third near‐infrared windows (1600‐1870 nm, near‐infrared‐III) provides a stable molecular vibrational imaging tool for lipid‐rich tissue owing to the first overtone transition of the CH bond at 1.7 μm. However, lacking high‐energy pulsed laser sources at 1.7 μm and the strong water absorption significantly limit the signal‐to‐noise ratio of the lipid imaging, especially for thin lipid tissues. To circumvent this barrier, we develop near‐infrared‐III double‐illumination optical‐resolution photoacoustic microscopy (DIOR‐PAM) for improving the sensitivity of label‐free lipid imaging. Using the same laser, DIOR‐PAM can enhance the sensitivity by nearly 100%, which we prove in the Monte Carlo simulation. We experimentally demonstrated 50% ~ 100% sensitivity enhancements on nonbiological and biological lipid‐rich samples.
Positively charged liposomes consisting of the KTTKS pentapeptide conjugated with rhodamine increase rhodamine toxicity in E. coli and zebrafish embryo
Authors: Hsieh Kai‐Hsuan , Hsu Chih‐Ying , Hung I‐Ju , Yeh Chih‐Ling , Chen Yau‐Hung , Cheng Chien‐Chung
Published: November 2020

Liposomes composed of cell‐penetrating peptide derivatives increased transport across the cell membrane. Conjugating rhodamine to a cell‐penetrating peptide increased the toxicity of rhodamine in E. coli and zebrafish embryos. A similar total protein inhibition pattern with different intensities, indicating that the interaction pathways of the rho‐KTTKS‐CONH2 monomer and liposomes were the same. It suggests that the rho‐KTTKS‐CONH2 liposomes showed higher toxicity because better transport across the cell membrane increased the effective concentration inside cells. The staining of zebrafish embryos using rho‐KTTKS‐CONH2 liposomes showed a longer retention time, suggesting that it can penetrate deeper tissues or organs in zebrafish.
Model‐Informed Dose Optimization in Pregnancy
Authors: Chaphekar Nupur , Caritis Steve , Venkataramanan Raman
Published: November 2020

Pregnancy is associated with several physiological changes that can alter the pharmacokinetics (PK) and pharmacodynamics of drugs. These may require dosing changes in pregnant women to achieve drug exposures comparable to the nonpregnant population. There is, however, limited information available on the PK and pharmacodynamics of drugs used during pregnancy. Practical difficulties in performing PK studies and potential liability issues are often the reasons for the availability of limited information. Over the past several years, there has been a rapid development in the application of various modeling strategies such as population PK and physiologically based PK modeling to provide guidance on drug dosing in this special patient population. Population PK models rely on measured PK data, whereas physiologically based PK models integrate physiological, preclinical, and clinical data to quantify changes in PK of drugs in various patient populations. These modeling strategies offer a promising approach to identify the drugs with PK changes during pregnancy and guide dose adjustment in pregnant women. This review focuses on PBPK modeling to guide drug therpay in pregnancy.
Applications of Physiologically Based Pharmacokinetic Modeling of Rivaroxaban—Renal and Hepatic Impairment and Drug‐Drug Interaction Potential
Authors: Willmann Stefan , Coboeken Katrin , Kapsa Stefanie , Thelen Kirstin , Mundhenke Markus , Fischer Kerstin , Hügl Burkhard , Mück Wolfgang
Published: November 2020

The non–vitamin K antagonist oral anticoagulant rivaroxaban is used in several thromboembolic disorders. Rivaroxaban is eliminated via both metabolic degradation and renal elimination as unchanged drug. Therefore, renal and hepatic impairment may reduce rivaroxaban clearance, and medications inhibiting these clearance pathways could lead to drug‐drug interactions. This physiologically based pharmacokinetic (PBPK) study investigated the pharmacokinetic behavior of rivaroxaban in clinical situations where drug clearance is impaired. A PBPK model was developed using mass balance and bioavailability data from adults and qualified using clinically observed data. Renal and hepatic impairment were simulated by adjusting disease‐specific parameters, and concomitant drug use was simulated by varying enzyme activity in virtual populations (n = 1000) and compared with pharmacokinetic predictions in virtual healthy populations and clinical observations. Rivaroxaban doses of 10 mg or 20 mg were used. Mild to moderate renal impairment had a minor effect on area under the concentration‐time curve and maximum plasma concentration of rivaroxaban, whereas severe renal impairment caused a more pronounced increase in these parameters vs normal renal function. Area under the concentration‐time curve and maximum plasma concentration increased with severity of hepatic impairment. These effects were smaller in the simulations compared with clinical observations. AUC and Cmax increased with the strength of cytochrome P450 3A4 and P‐glycoprotein inhibitors in simulations and clinical observations. This PBPK model can be useful for estimating the effects of impaired drug clearance on rivaroxaban pharmacokinetics. Identifying other factors that affect the pharmacokinetics of rivaroxaban could facilitate the development of models that approximate real‐world pharmacokinetics more accurately.
Surface enhanced Raman spectroscopy‐based evaluation of the membrane protein composition of the organohalide‐respiring Sulfurospirillum multivorans
Authors: Cialla‐May Dana , Gadkari Jennifer , Winterfeld Andreea , Hübner Uwe , Weber Karina , Diekert Gabriele , Schubert Torsten , Goris Tobias , Popp Jürgen
Published: November 2020

Bacteria often employ different respiratory chains that comprise membrane proteins equipped with various cofactors. Monitoring the protein inventory that is present in the cells under a given cultivation condition is often difficult and time‐consuming. One example of a metabolically versatile bacterium is the microaerophilic organohalide‐respiring Sulfurospirillum multivorans. Here, we used surface enhanced Raman spectroscopy (SERS) to quickly identify the cofactors involved in the respiration of S. multivorans. We cultured the organism with either tetrachloroethene (perchloroethylene, PCE), fumarate, nitrate, or oxygen as electron acceptors. Because the corresponding terminal reductases of the four different respiratory chains harbor different cofactors, specific fingerprint signals in SERS were expected. Silver nanostructures fabricated by means of electron beam lithography were coated with the membrane fractions extracted from the four S. multivorans cultivations, and SERS spectra were recorded. In the case of S. multivorans cultivated with PCE, the recorded SERS spectra were dominated by Raman peaks specific for Vitamin B12. This is attributed to the high abundance of the PCE reductive dehalogenase (PceA), the key enzyme in PCE respiration. After cultivation with oxygen, fumarate, or nitrate, no Raman spectral features of B12 were found.
Analysis of scarlet elf cup (Sarcoscypha coccinea) carotenoids in vivo by Raman spectroscopy
Authors: Dzhagan Volodymyr , Dzhagan Veronika , Hreshchuk Oleksandr , Taran Natalia
Published: November 2020

Raman spectroscopy, an established optical method of remote diagnostics of pigments and dyes, is applied here for the first time to the cup fungus Scarlet elf cup (Sarcoscypha coccinea or Plectania coccinea or Peziza coccinea) from the order Pezizales (Ascomycota). As‐collected fungi samples are investigated, not subject to any treatment. The dominant vibrational features in the acquired in vivo spectrum, around 1000, 1150, and 1500 cm−1, respectively, clearly indicate it is dominated by carotenoid(s). Contrary to most previous Raman studies of carotenoids, including few studies of fungi, which focused on the latter three strongest fundamental vibrations, we have resolved and analyzed in detail 30 vibrational bands, including rarely studied wavenumber range above 2000 cm−1. We discuss in detail the inferred from our spectral analysis carotenoid species in comparison with those previously reported for Sarcoscypha coccinea by other methods. In particular, we suggest two characteristic ring vibrations, at 1131 and 1283 cm−1, to be used as a measure of the ratio of astaxanthin and plectaniaxanthin to β‐carotene and lycopene in this and similar fungi. In addition, we report the fluorescence spectrum of this fungal species, present as background in the Raman spectrum at visible excitation. The results obtained in this work will facilitate subsequent more quantitative studies of carotenoid composition in other kinds of fungi and other microorganisms using Raman spectroscopy in combination with other techniques.
Oil‐in‐water Pickering emulsion stabilization with oppositely charged polysaccharide particles: chitin nanocrystals/fucoidan complexes
Authors: Liu Zhao , Hu Miao , Zhang Shuang , Jiang Lianzhou , Xie Fengying , Li Yang
Published: November 2020

BACKGROUND

Chitin nanocrystals (ChN) are insoluble particles that can be used as stabilizers for Pickering emulsions. Their unique cationic properties and antibacterial activity have generated considerable interest among researchers. However, ChN have remained largely underexplored. Furthermore, the droplets of the emulsions stabilized by ChN are as large as 10–100 μm, and their physical stability requires further improvement. Some studies have shown that the spontaneous reaction of oppositely charged particles can effectively stabilize the emulsions. Positively charged ChN and negatively charged fucoidan (F) were therefore compounded to stabilize Pickering emulsions, and the stability of these emulsions was analyzed qualitatively.

RESULTS

The results showed that the composite particles comprising two polysaccharides in a mass ratio of 1:1 and at a pH of 2 (ChN1‐F1‐pH 2) possessed the lowest sulfate content (20.1%) and almost zero potential (−3 mV), indicating a high degree of neutralization of the positively charged amino group in ChN and the negatively charged sulfate group in F. Meanwhile, ChN1‐F1‐pH 2 displayed a dense network structure that improved the dispersibility and wettability (contact angle = 9.3°). Fourier transform infrared spectroscopy results confirmed that ChN and F were effectively combined through electrostatic interaction or neutralization to produce a polyelectrolyte complex. Furthermore, the particle size of the Pickering emulsion stabilized by ChN‐F was significantly reduced, and the maximum size did not exceed 10 μm; the physical and storage stability also improved. The ChN1‐F1‐pH 2 emulsion presented excellent storage stability; in particular, the emulsions stabilized by ChN1‐F1‐pH 5 and ChN1‐F1‐pH 6 exhibited excellent flocculation stabilities.

CONCLUSION

The size of the emulsion droplets stabilized by the oppositely charged polysaccharide particles (ChN‐F complexes) reduced significantly. Furthermore, by changing the mass ratio and pH, the microstructure and binding degree of the complexes can be adjusted, thereby promoting their adsorption on the oil–water interface and improving the stability of the Pickering emulsion. © 2020 Society of Chemical Industry
Textural and structural properties of a κ‐carrageenan–konjac gum mixed gel: effects of κ‐carrageenan concentration, mixing ratio, sucrose and Ca2+ concentrations and its application in milk pudding
Authors: Wang Xin , Zhou Dengyun , Guo Qi , Liu Caiyun
Published: November 2020

BACKGROUND

Mixtures of carrageenan and konjac gum are useful for specific applications in gel‐based foods. Focusing on the changes of textural and structural properties, the effects of κ‐carrageenan and konjac ratio and sucrose and Ca2+ concentrations on mixed gels were studied in this research. Furthermore, application of κ‐carrageenan–konjac gum mixed gel to milk puddings was investigated.

RESULTS

There was a better synergistic effect when the ratio of κ‐carrageenan and konjac was 7:3. The mixed gel containing 10 g kg−1 κ‐carrageenan–konjac gum was characterized by higher hardness, chewiness, adhesiveness and resilience and denser network structure. Besides, the addition of 5–10 wt% sucrose or 0.02 wt% Ca2+ could enhance the hardness, chewiness and adhesiveness of the mixed gel, as well as affording a denser network structure. For milk pudding, moderate hardness, chewiness and resilience could be obtained by adding 1.5 g kg−1 κ‐carrageenan–konjac gum mixture.

CONCLUSIONS

This research provides useful information for the formation of κ‐carrageenan–konjac gum gel and its application in milk pudding. © 2020 Society of Chemical Industry
Restoring soil carbon and chemical properties through silvopastoral adoption in the Colombian Amazon region
Authors: Olaya‐Montes Andres , Llanos‐Cabrera Maria P. , Cherubin Maurício R. , Herrera‐Valencia Wilmer , Ortiz‐Morea Fausto A. , Silva‐Olaya Adriana M.
Published: November 2020

Silvopastoral systems (SPS) have been widely implemented in the Colombian Amazon region to improve pastures involving a greater diversity of species, soil tillage, fertilization, and higher stocking rate, which can induce changes in soil properties and functions. This study aimed to evaluate soil chemical properties and carbon sequestration changes due to the transition from traditional pastures to silvopastoral systems. The study was conducted in the Colombian Amazon region, specifically in La Montañita and El Doncello Counties, in Caquetá, the second most important hotspot of deforestation in the entire Amazon basin. In each study site, we established a chronosequence consisting of three areas following the typical land‐use change at the region: (i) native vegetation, (ii) traditional pasture, and (iii) silvopastoral system. We found that agricultural practices involving liming and tillage, performed under the silvopastoral management, contributed to reducing soil active acidity and exchangeable acidity with soil pH increasing from 3.8 to 4.3 and H++Al3+ decreasing from 5.8 to 2.3 cmolc kg−1. These alterations favored increases in Ca2+ and Mg2+ contents mainly, increasing the base saturation from 17% in traditional pastures to 55% under silvopastoral systems. The synergic effect of the mix of grasses and trees under silvopastoral management improved soil micronutrient contents and modified soil C stocks in 20–30 cm layer. A rate of soil C accretion of 0.26 Mg ha−1 yr−1 for the 0–30 cm detected in silvopastoral systems suggests that its implementation could be a promising tool for C sequestration in tropical regions, capable of restoring soil functioning of degraded areas.
Stability and flip bifurcation of a three‐dimensional exponential system of difference equations
Authors: Mylona Chrysoula , Papaschinopoulos Garyfalos , Schinas Christos J.
Published: November 2020

In this paper, we study the stability of the zero equilibrium and the occurrence of flip bifurcation of the following system of difference equations:whereai,bi,ci,di, andki, for ,2, and3, are real constants and the initial valuesx0,y0, andz0are real numbers. We study the stability of this system in the special case when one of the eigenvalues is equal to−1 and the remaining eigenvalues have absolute value less than 1, using the center manifold theory.
Technical Note: ADAM PETer – An anthropomorphic, deformable and multimodality pelvis phantom with positron emission tomography extension for radiotherapy
Authors: Gillmann Clarissa , Homolka Noa , Johnen Wibke , Runz Armin , Echner Gernot , Pfaffenberger Asja , Mann Philipp , Schneider Verena , Hoffmann Aswin L. , Troost Esther G. C. , Koerber Stefan A. , Kotzerke Jörg , Beuthien‐Baumann Bettina
Published: November 2020

Objective

To develop an anthropomorphic, deformable and multimodal pelvis phantom with positron emission tomography extension for radiotherapy (ADAM PETer).

Methods

The design of ADAM PETer was based on our previous pelvis phantom (ADAM) and extended for compatibility with PET and use in 3T magnetic resonance imaging (MRI). The formerly manually manufactured silicon organ surrogates were replaced by three‐dimensional (3D) printed organ shells. Two intraprostatic lesions, four iliac lymph node metastases and two pelvic bone metastases were added to simulate prostate cancer as multifocal and metastatic disease. Radiological properties [computed tomography (CT) and 3T MRI] of cortical bone, bone marrow and adipose tissue were simulated by heavy gypsum, a mixture of Vaseline and K2HPO4 and peanut oil, respectively. For soft tissues, agarose gels with varying concentrations of agarose, gadolinium (Gd) and sodium fluoride (NaF) were developed. The agarose gels were doped with patient‐specific activity concentrations of a Fluorine‐18 labelled compound and then filled into the 3D printed organ shells of prostate lesions, lymph node and bone metastases. The phantom was imaged at a dual energy CT and a 3T PET/MRI scanner.

Results

The compositions of the soft tissue surrogates are the following (given as mass fractions of agarose[w%]/NaF[w%]/Gd[w%]): Muscle (4/1/0.027), prostate (1.35/4.2/0.011), prostate lesions (2.25/4.2/0.0085), lymph node and bone metastases (1.4/4.2/0.025). In all imaging modalities, the phantom simulates human contrast. Intraprostatic lesions appear hypointense as compared to the surrounding normal prostate tissue in T2‐weighted MRI. The PET signal of all tumors can be localized as focal spots at their respective site. Activity concentrations of 12.0 kBq/mL (prostate lesion), 12.4 kBq/mL (lymph nodes) and 39.5 kBq/mL (bone metastases) were measured.

Conclusion

The ADAM PETer pelvis phantom can be used as multimodal, anthropomorphic model for CT, 3T‐MRI and PET measurements. It will be central to simulate and optimize the technical workflow for the integration of PET/MRI‐based radiation treatment planning of prostate cancer patients.
Invasive Blue Catfish in the Chesapeake Bay Region: A Case Study of Competing Management Objectives
Authors: Fabrizio Mary C. , Nepal Vaskar , Tuckey Troy D.
Published: November 2020

Freshwater fishes have been introduced outside their native range to establish recreational fisheries, but management conflicts arise when such introductions also result in potentially harmful effects on native species. In this case study, we focus on Blue Catfish Ictalurus furcatus, which were introduced in the Chesapeake Bay region and are now considered invasive. In many tidal tributaries, Blue Catfish have increased dramatically in abundance, expanded into high-salinity habitats (up to 21.8 psu), and negatively affected native species, prompting calls for the development of an effective management plan. However, management of this conflict species is complicated by multiple competing objectives, including control of population size, maintenance of trophy fisheries, and expansion of commercial fisheries for Blue Catfish. Seven management recommendations were advanced by the Invasive Catfishes Work Group to control the spread and limit the ecological impacts of Blue Catfish on native species. We highlight opportunities for addressing these complex management issues and guide our suggestions using results from research on invasive Blue Catfish ecology and population dynamics, as well as management of invasive species in general. A formal approach, such as structured decision analysis, is required to resolve conflicts among user groups and to address the wicked problem of Blue Catfish in the Chesapeake Bay region.