bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine learning approach for distinguishing malignant and benign lung nodules utilizing standardized perinodular parenchymal features from CT
Authors: Uthoff Johanna , Stephens Matthew J. , Newell John D. , Hoffman Eric A. , Larson Jared , Koehn Nicholas , De Stefano Frank A. , Lusk Chrissy M. , Wenzlaff Angela S. , Watza Donovan , Neslund‐Dudas Christine , Carr Laurie L. , Lynch David A. , Schwartz Ann G. , Sieren Jessica C.
Published: May 2019

Purpose

Computed tomography (CT) is an effective method for detecting and characterizing lung nodules in vivo. With the growing use of chest CT, the detection frequency of lung nodules is increasing. Noninvasive methods to distinguish malignant from benign nodules have the potential to decrease the clinical burden, risk, and cost involved in follow‐up procedures on the large number of false‐positive lesions detected. This study examined the benefit of including perinodular parenchymal features in machine learning (ML) tools for pulmonary nodule assessment.

Methods

Lung nodule cases with pathology confirmed diagnosis (74 malignant, 289 benign) were used to extract quantitative imaging characteristics from computed tomography scans of the nodule and perinodular parenchyma tissue. A ML tool development pipeline was employed using k‐medoids clustering and information theory to determine efficient predictor sets for different amounts of parenchyma inclusion and build an artificial neural network classifier. The resulting ML tool was validated using an independent cohort (50 malignant, 50 benign).

Results

The inclusion of parenchymal imaging features improved the performance of the ML tool over exclusively nodular features (P < 0.01). The best performing ML tool included features derived from nodule diameter‐based surrounding parenchyma tissue quartile bands. We demonstrate similar high‐performance values on the independent validation cohort (AUC‐ROC = 0.965). A comparison using the independent validation cohort with the Fleischner pulmonary nodule follow‐up guidelines demonstrated a theoretical reduction in recommended follow‐up imaging and procedures.

Conclusions

Radiomic features extracted from the parenchyma surrounding lung nodules contain valid signals with spatial relevance for the task of lung cancer risk classification. Through standardization of feature extraction regions from the parenchyma, ML tool validation performance of 100% sensitivity and 96% specificity was achieved.
Euthanasia via CO2 inhalation causes premature cortical granule exocytosis in mouse oocytes and influences in vitro fertilization and embryo development
Authors: Wuri Liga , Agca Cansu , Agca Yuksel
Published: May 2019

Generation of high quality mouse metaphase II oocytes is an integral part for efficient in vitro fertilization (IVF), and subsequent embryo production for reproductive studies and genome banking. The main objectives of this study were to investigate the impact of various euthanasia methods on IVF, embryo development, and subcellular structures of MII mouse oocytes. Following superovulation regimen, female mice were euthanized by high flow CO2 (H CO2), low flow CO2 (L CO2), or cervical dislocation (CD). The MII oocytes obtained from these mice were evaluated for subcellular integrity by assessing their cortical granules and F‐actin. Furthermore, fertilization and subsequent embryonic development competence up to blastocyst stage were also evaluated in vitro. The oocytes collected from females euthanized by CD resulted in significantly higher two‐cell development rates (p = 0.028) and subsequently lead to in higher embryo development rates (p = 0.027) compared with oocytes from females euthanized by L CO2. The cortical granule integrity analysis revealed significantly higher rate of premature cortical granules exocytosis (PCGE) for L CO2 group compared with CD and H CO2 groups (p < 0.001). These data collectively suggest that CO2 associated PCGE during euthanasia procedure is the main cause of decreased IVF rates and CD is the optimal euthanasia method for the purpose of obtaining good quality MII oocytes for mouse IVF and other reproductive studies.
Ion channels and signaling pathways used in the fast polyspermy block
Authors: Wozniak Katherine L. , Carlson Anne E.
Published: May 2019

Fertilization of an egg by multiple sperms, polyspermy, is lethal to most sexually reproducing species. To combat the entry of additional sperm into already fertilized eggs, organisms have developed various polyspermy blocks. One such barrier, the fast polyspermy block, uses a fertilization‐activated depolarization of the egg membrane to electrically inhibit supernumerary sperm from entering the egg. The fast block is commonly used by eggs of oviparous animals with external fertilization. In this review, we discuss the history of the fast block discovery, as well as general features shared by all organisms that use this polyspermy block. Given the diversity of habitats of external fertilizers, the fine details of the fast block‐signaling pathways differ drastically between species, including the identity of the depolarizing ions. We highlight the known molecular mediators of these signaling pathways in amphibians and echinoderms, with a fine focus on ion channels that signal these fertilization‐evoked depolarizations. We also discuss the investigation for a fast polyspermy block in mammals and teleost fish, and we outline potential fast block triggers. Since the first electrical recordings made on eggs in the 1950s, the fields of developmental biology and electrophysiology have substantially matured, and yet we are only now beginning to discern the intricate molecular mechanisms regulating the fast block to polyspermy.
Optimized and accelerated 19F‐MRI of inhaled perfluoropropane to assess regional pulmonary ventilation
Authors: Neal Mary A. , Pippard Benjamin J. , Hollingsworth Kieren G. , Maunder Adam , Dutta Prosenjit , Simpson A. John , Blamire Andrew M. , Wild James M. , Thelwall Peter E.
Published: May 2019

Purpose

To accelerate 19F‐MR imaging of inhaled perfluoropropane using compressed sensing methods, and to optimize critical scan acquisition parameters for assessment of lung ventilation properties.

Methods

Simulations were performed to determine optimal acquisition parameters for maximal perfluoropropane signal‐to‐noise ratio (SNR) in human lungs for a spoiled gradient echo sequence. Optimized parameters were subsequently employed for 19F‐MRI of inhaled perfluoropropane in a cohort of 11 healthy participants using a 3.0 T scanner. The impact of 1.8×, 2.4×, and 3.0× undersampling ratios on 19F‐MRI acquisitions was evaluated, using both retrospective and prospective compressed sensing methods.

Results

3D spoiled gradient echo 19F‐MR ventilation images were acquired at 1‐cm isotropic resolution within a single breath hold. Mean SNR was 11.7 ± 4.1 for scans acquired within a single breath hold (duration = 18 s). Acquisition of 19F‐MRI scans at shorter scan durations (4.5 s) was also demonstrated as feasible. Application of both retrospective (n = 8) and prospective (n = 3) compressed sensing methods demonstrated that 1.8× acceleration had negligible impact on qualitative image appearance, with no statistically significant change in measured lung ventilated volume. Acceleration factors of 2.4× and 3.0× resulted in increasing differences between fully sampled and undersampled datasets.

Conclusion

This study demonstrates methods for determining optimal acquisition parameters for 19F‐MRI of inhaled perfluoropropane and shows significant reduction in scan acquisition times (and thus participant breath hold duration) by use of compressed sensing.
Short echo time relaxation‐enhanced MR spectroscopy reveals broad downfield resonances
Authors: Gonçalves Sónia I. , Ligneul Clémence , Shemesh Noam
Published: May 2019

Purpose

Most MR spectroscopy (MRS) pulse sequences rely on broadband excitation with water saturation and typically focus on upfield signals. By contrast, the downfield spectrum, which contains many potentially useful resonances, is typically not targeted because conventional water‐suppressed techniques indirectly saturate the labile protons through exchange. Relaxation‐enhanced MRS (RE‐MRS) uses frequency‐selective excitation while actively avoiding bulk water perturbation, thereby enabling high‐quality downfield spectroscopy. However, RE‐MRS typically requires very long (typically >40 ms) echo times (TEs) due to its localization module, which inevitably decreases sensitivity and filters shorter T2 components. Here, we overcome this limitation by combining RE‐MRS and image selected in vivo spectroscopy (ISIS) localization, abbreviated iRE‐MRS, which in turn allows very short TEs (5 ms using our hardware).

Methods

Experiments were performed in vitro for validation as well as and in in vivo rat brains at 9.4T.

Results

The new iRE‐MRS methodology was validated in phantoms where good performance was noted. When the downfield spectrum was investigated at short TEs in in vivo rat brains, iRE‐MRS provided very high sensitivity; the ensuing downfield spectra encompassed numerous broad peaks, as well as a broad baseline. All downfield spectral peaks were highly attenuated by increasing TEs as well as by applying water saturation, although to different extent. The signal ratios also varied between TEs, suggesting that exchange rates are different among the downfield signals.

Conclusions

Short‐TE iRE 1H downfield MRS opens new directions in the investigation of in vivo downfield metabolites and their role on healthy and disease processes.
Genetic Population Structure of White Grunt in the Southeastern United States
Authors: O'Donnell Timothy P. , Reichert Marcel J. M. , Darden Tanya L.
Published: May 2019

The White Grunt Haemulon plumierii is a reef-associated coastal fish species in the western Atlantic Ocean that occurs from the Chesapeake Bay south through the Gulf of Mexico and along the eastern coast of Brazil. In U.S. waters, there are recreational and commercial fisheries for White Grunt, but there are currently no size regulations in the recreational fishery and no size or trip regulations in the commercial fishery. A stock assessment for White Grunt is necessary prior to enacting any potential future regulations, and informed stock boundaries must first be delineated. Studies finding regional differences in genetic population structure and growth rates for White Grunt in the southeastern USA have resulted in uncertainty of stock definition. The objective of the present study was to evaluate the genetic population structure of White Grunt in the southeastern USA and the U.S. Virgin Islands using 10 microsatellite markers. Pairwise genetic distances, allele frequency distributions, principal coordinates analysis, and Bayesian clustering results indicated that White Grunt should be separated into four distinct populations among the regions sampled: the Carolinas (North Carolina and South Carolina); southeast Florida, including the Florida Keys (from Cape Canaveral to Key West); eastern Gulf of Mexico (western coast of Florida north of Key West); and the U.S. Caribbean. The genetic differentiation results presented here, along with regional growth studies, warrant the management of White Grunt as three separate stocks in the Atlantic Ocean bordering the continental USA: the Carolinas, southeast Florida and Florida Keys, and the eastern Gulf of Mexico, with at least one other separate stock in the Caribbean Sea.
Advances in pile integrity testing
Authors: Ertel Jens-Peter , Niederleithinger Ernst , Grohmann Maria
Published: May 2019

For decades, the low‐strain impact integrity testing using a hammer blow is well established as a method of quality assurance for various pile types. However, this method has its limitations. Our research and development focuses on improving the excitation signal using a shaker system in contrast to the standard hammer method. Another approach is to increase the amount of sensors used during testing. The purpose is to identify the direction of wave propagation that gives advantages under difficult conditions, such as piles below structures.

Pile integrity testing using a shaker system was performed on two 11‐m‐long piles of 90 cm in diameter. While one pile was intact, the other one showed a flaw at approximately 3.5 m below pile top, which was confirmed by standard pile integrity testing in 2012. A logarithmic sweep between 500 Hz and 1 KHz of 0.1 s was used as the input signal, being vertically injected into the pile. Prior to that, simulations on similar pile geometries showed that the depth of the pile toe as well as flaws within the pile can be extracted by applying regularised deconvolution. The result is the impulse response in the time domain.

The application of deconvolution on the measured signals shows that it is possible to identify the pile length, but it is more difficult to clearly extract the flaw’s position in the pile. Additional digital signal processing techniques and the improvement of the regularised deconvolution method and the experimental setup need to be investigated.

Another way to improve the pile integrity testing method is to use a multi‐channel sensor arrangement. By arranging several accelerometers vertically along the accessible part of the pile shaft, it is possible to distinguish between downward and upward travelling waves. Furthermore, it is possible to estimate the unknown wave speed, which gives the possibility of more accurate pile length calculations. The method was evaluated successfully during a measurement campaign of a slab foundation with subjacent piles. In 20 of 28 cases, the pile length could be detected accurately.
China–Pakistan Economic Corridor (CPEC) development projects and entrepreneurial potential of locals
Authors: Kanwal Shamsa , Pitafi Abdul Hameed , Pitafi Adnan , Nadeem Muhammad Athar , Younis Amna , Chong Ren
Published: May 2019

This research explores a very important issue arising from the initiation of China–Pakistan Economic Corridor (CPEC) in Pakistan, as the major impact seems to be focused towards small businesses and how they will cope in this competitive market once Chinese businesses enter in the country. According to scholars and officials, CPEC will generate several business opportunities for the local Pakistani community. However, studies related to the CPEC project are limited and only focused on the development of the CPEC project in various aspects alone. The existing study examined the local entrepreneur's attitude and intention in the context of CPEC using a sample of 255 survey questionnaires. Structural equation modeling was used to test the proposed hypotheses. Data were gathered from the existing business community in Karachi, Pakistan. The results validated most of the hypotheses showing positive attitude towards entrepreneurs and intention towards CPEC development project. Specifically, local transportation and accessibility of cities show a significant relationship with a positive attitude. Similarly, the attitude of entrepreneurs also shows a positive relationship with entrepreneur's intention towards CPEC development projects. Findings have important theoretical and practical implications for policymakers of CPEC in creating an overall entrepreneurial ecosystem.
Transitional care practices, services, and delivery in childhood cancer survivor programs: A survey study of U.S. survivorship providers
Authors: Sadak Karim Thomas , Szalda Dava , Lindgren Bruce R. , Kinahan Karen E. , Eshelman‐Kent Debra , Schwartz Lisa A. , Henderson Tara , Freyer David R.
Published: May 2019

Purpose

There are limited reports describing transition of young adult childhood cancer survivors (CCS) from pediatric to adult‐focused survivorship care. The purpose of this study was to characterize current transitional care practices in the United States.

Project Description

An online survey was sent to one preselected respondent at 163 Children's Oncology Group member institutions in the United States. Data were collected about (i) the availability and type of long‐term follow‐up services for adult CCS and (ii) policies and procedures for transitioning. Logistic regression was used to evaluate factors related to care for CCS.

Results

The response rate was 60% (97/163). Eighty‐one respondents (84%) represented centers with specialized pediatric‐focused CCS programs. Thirty‐nine percent (38/97) of programs delivered specialized transitional care for adult CCS. Adult‐centered care was delivered in both pediatric (39%, 15/38) and adult oncology clinics (39%, 15/38). The most common perceived transition barriers were lack of available partnering adult providers and adult providers’ lack of knowledge regarding CCS. The larger the program in terms of new diagnoses, the more likely they were to offer formal transitional care (<50 vs >200: odds ratios [OR] 20.0; 95% CI 3.2, 100.0, P = 0.004).

Conclusions

A variety of models are utilized for delivering care to adult CCS. Our results suggest that interventions to establish effective partnerships with adult providers on appropriate care of CCS may facilitate expanded availability of these services.
The Role of p38 MAPK in Triacylglycerol Accumulation during Apoptosis
Authors: Li Nasi , Saitou Marie , Atilla‐Gokcumen Gunes Ekin
Published: May 2019

Lipids are emerging as key regulators of apoptosis. Specific lipid species are associated with apoptosis with important functional roles, but the understanding of the regulation of these lipid species is still limited. It has been previously shown by our laboratory that polyunsaturated triacylglycerols accumulate and get stored within lipid droplets during apoptosis via activated glycerolipid biosynthesis. In this work, the biochemical mechanisms that result in the activation of glycerolipid biosynthesis and, consequently, triacylglycerol and lipid droplet accumulation during apoptosis are investigated. The transcriptomes of control and apoptotic HCT‐116 cells are compared and gene enrichment analysis revealed the upregulation of p38 mitogen‐activated protein kinase (MAPK). It is shown that p38 MAPK regulates triacylglycerol biosynthesis through diacylglycerol acyltransferase1 during apoptosis. Perilipin 2 and cytosolic phospholipase A2delta are also shown to be involved in lipid droplet and polyunsaturated triacylglycerol accumulation in this process. Overall, the results provide new insights into the upregulation of glycerolipid synthesis during apoptosis.
Exploring emotion regulation as a mediator of the relationship between resilience and distress in cancer
Authors: Vaughan Emma , Koczwara Bogda , Kemp Emma , Freytag Corinna , Tan Wilson , Beatty Lisa
Published: May 2019

Objectives

Distress in patients with cancer is a significant problem that affects up to 32% of patients. Yet research indicates that 35% of cancer patients do maintain high levels of well‐being. Resilience is one psychological factor implicated as being protective against distress; however, the mechanisms for this relationship are currently unknown. The present study aimed to explore emotion regulation as a potential mediator of the relationship between resilience and distress.

Methods

A cross‐sectional survey examining emotional regulation, resilience, and distress was completed by 227 patients from two hospitals with heterogeneous cancer types. Measures included the Difficulties in Emotion Regulation Scale (DERS), the Connor Davidson Resilience Scale, and the Depression, Anxiety, Stress Scale.

Results

Difficulties in emotion regulation and resilience explained 33.2% of the variance in distress. Resilience had a significant direct effect on distress, accounting for 15.8% of the variance. However, this effect was no longer significant when difficulties in emotion regulation were controlled for. The indirect effect through difficulties in emotion regulation was significant, b = 0.009, 95% CI [−0.013,−0.007], suggesting that the effect of resilience on distress was fully mediated by emotion regulation. Parallel mediation analyses also examined the differential effects of the six DERS subscales on the relationship between resilience and distress.

Conclusion

These findings suggest that emotion regulation is an important mediator of resilience in cancer. Hence, in patients with cancer, difficulties in emotion regulation (and the DERS specifically) might be a useful focus for screening for patients at risk of distress.
Introducing the Prescribing Skills Assessment box sets
Authors: Dowden Angela
Published: May 2019

All recently‐qualified medics will be familiar with the Prescribing Safety Assessment (PSA), an examination that must be passed before doctors can move on to their F2 foundation year. Now, the British Pharmacological Society, which co‐created the PSA, is championing wider use of its Prescribing Skills Assessment – the cloudbased learning platform that underpins the PSA – and is introducing a series of ‘box sets’ to test prescribers in various areas of prescribing.
Nyxoid (naloxone) nasal spray for opioid overdose
Authors: Parsons Graham
Published: May 2019

Nyxoid (naloxone) 1.8mg nasal spray was recently launched as emergency therapy for known or suspected opioid overdose in both medical and non‐medical settings. This article summarises the product's indications, recommended use, advantages and disadvantages and place in therapy.
A Minimal Physiologically‐Based Pharmacokinetic Model for Tacrolimus in Living‐Donor Liver Transplantation: Perspectives Related to Liver Regeneration and the cytochrome P450 3A5 (CYP3A5) Genotype
Authors: Itohara Kotaro , Yano Ikuko , Tsuzuki Tetsunori , Uesugi Miwa , Nakagawa Shunsaku , Yonezawa Atsushi , Okajima Hideaki , Kaido Toshimi , Uemoto Shinji , Matsubara Kazuo
Published: May 2019

In adult patients after living‐donor liver transplantation, postoperative days and the cytochrome P450 3A5 (CYP3A5) genotype are known to affect tacrolimus pharmacokinetics. In this study, we constructed a physiologically‐based pharmacokinetic model adapted to the clinical data and evaluated the contribution of liver regeneration as well as hepatic and intestine CYP3A5 genotypes on tacrolimus pharmacokinetics. As a result, liver function recovered immediately and affected the total body clearance of tacrolimus only during a limited period after living‐donor liver transplantation. The clearance was about 1.35‐fold higher in the recipients who had a liver with the CYP3A5*1 allele than in those with the CYP3A5*3/*3 genotype, whereas bioavailability was ~0.7‐fold higher in the recipients who had intestines with the CYP3A5*1 allele than those with CYP3A5*3/*3. In conclusion, the constructed physiologically‐based pharmacokinetic model clarified that the oral clearance of tacrolimus was affected by the CYP3A5 genotypes in both the liver and intestine to the same extent.
Critically Reviewing GraphoGame Across the World: Recommendations and Cautions for Research and Implementation of Computer‐Assisted Instruction for Word‐Reading Acquisition
Authors: McTigue Erin M. , Solheim Oddny Judith , Zimmer Wendi K. , Uppstad Per Henning
Published: May 2019

Overall, game‐based technology for early reading instruction has not robustly met the learning potentials of young readers. To better understand the effects and limitations of computer‐assisted instruction in classrooms, researchers have called for more critical attention to learning theory, methodological selection, and context for learning. GraphoGame (GG), an adaptive serious game designed to prevent reading difficulties through the promotion of sound–symbol connections, has been implemented in over 20 countries. Therefore, the GG research base provides an opportunity to synthesize research on a single computer‐assisted instruction across diverse contexts. Surprisingly, despite extensive use and further implementation plans, no review has yet synthesized GG's effects. Specifically, this systematic literature review, with an embedded meta‐analysis, synthesized 28 empirical studies for theory, methodological quality, and outcomes. The GG research base was dominated by theories of reading disabilities and psycholinguistics. Methodologically, quantitative methods, focusing on phonological and decoding outcome measures only, were most common. The meta‐analysis (n = 19), measuring GG's impact on word‐reading outcomes, did not yield an overall meaningful effect size (g = −0.02). However, among moderators (language complexity, duration of intervention, and adult interaction), adult interaction was significant, favoring implementation contexts with high levels of adult interaction. Specifically, studies with high adult interaction produced an average positive effect size (g = 0.48), which suggests implications for classroom use. Regarding future research, the authors recommend stronger clarity of theory, attention to learning context, and a more purposeful collection of process data, which can be obtained through greater plurality of methodology.
Developing a project sustainability index for sustainable development in transnational public–private partnership projects
Authors: Chen Chuan , Yu Yao , Osei‐Kyei Robert , Chan Albert Ping Chuen , Xu Jing
Published: May 2019

During the last couple of years, sustainability has become topical in transnational public–private partnership (TPPP) projects primarily because of the enormous impact TPPP projects have on the environment, economic, and well‐being of people. This paper aims to develop a model that could be used to evaluate the sustainability levels of TPPP projects. The proposed model consists of four categories of social responsibility factors; these include economic, environment, social, and people‐oriented factors. Of the four categories, social factors obtained the highest coefficient (i.e., 0.255) in the TPPP sustainability index equation. The substantive model will enable practitioners to quantify the sustainability levels of TPPP projects prior to their implementations. Moreover, the outputs of this study inform private investors of the key areas to focus on to enhance sustainable development through TPPP project implementations.
Sequential trials in the context of competing risks: Concepts and case study, with R and SAS code
Authors: Baayen C. , Volteau C. , Flamant C. , Blanche P.
Published: May 2019

Sequential designs and competing risks methodology are both well established. Their combined use has recently received some attention from a theoretical perspective, but their joint application in practice has been discussed less. The aim of this paper is to provide the applied statistician with a basic understanding of both sequential design theory and competing risks methodology and how to combine them in practice. Relevant references to more detailed theoretical discussions are provided, and all discussions are illustrated using a real case study. Extensive R and SAS code is provided in the online Supplementary Material.
Electrochemical Sensors and Biosensors Based on Graphene Functionalized with Metal Oxide Nanostructures for Healthcare Applications
Authors: Kumar Sudesh , Bukkitgar Shikandar D. , Singh Supriya , Pratibha  , Singh Vanshika , Reddy Kakarla Raghava , Shetti Nagaraj P. , Venkata Reddy Ch. , Sadhu Veera , Naveen S.
Published: May 2019

Graphene has attracted wide consideration in recent years to the assembly of sensitive sensors and biosensors due to its unique and remarkable physical and electrochemical properties. Moreover, graphene, as an essential two‐dimensional carbon material with remarkably high quartz and electronic superiority, has also received significant research attention. This review presents the different synthesis techniques of graphene; graphene functionalized based electrochemical sensors and biosensors for various health care appellations. Further, were discussed on the basis of enhanced catalytic activity, improved detection limit in conjunction with sensitivity, and selectivity. Synergistic action of graphene and metal oxide nanostructure has contributed towards high activity as a biosensing material. The results with different sensors and biosensors for the detection of significant biomarkers such as protein sensor, electrochemical immune sensor, phytochrome sensor, cholesterol biosensor glucose, hydrogen peroxide, and nicotinamide adenine dinucleotide detection sensor etc., and highlighted the use of graphene and functionalized graphene in different sensing platforms. Finally, the challenges related to less aggregated graphene‐based electrochemical sensors and biosensors as well as future research directions are discussed.
Total Synthesis of (3R, 4 S)‐4‐Hydroxylasiodiplodin via Ring Closing Metathesis Protocol
Authors: Reddy Julakanti Satyanarayana , Manimala Patel , Gangababu Marri , Rammohan Aluru , Yadav Jillu Singh
Published: May 2019

Total synthesis of (3R, 4 S)‐4‐Hydroxylasiodiplodin has been accomplished through convergent strategy using D‐isoascorbic acid and trihydroxybenzoic acid as the starting materials in an optimal reaction sequence. The salient features of the synthesis are the utilization of Stille coupling, trans‐esterification and Ring‐Closing Metathesis (RCM).
ICT‐Based Blue‐Emitting Dual‐Functional Probe (Ugi EML BLUE) for Bio‐Imaging and Cytotoxic Activities on HeLa Cells
Authors: Puthumana Shyam Shankar Eramangalam , Damodaran Bahulayan
Published: May 2019

An Intramolecular Charge Transfer (ICT) based blue emitting fluorescent probe (Ugi EML BLUE) has been developed and its binding properties against human CDK2 protein have been studied via docking methods. The docking studies showed that, Ugi EML BLUE can effectively interact with the ATP binding sites of CDK2. The positive results obtained from the docking studies have been extended to the bio‐imaging as well as antineoplastic applications in HeLa cells. The in vitro biological activity studies revealed the remarkable potential of Ugi EML BLUE as a dual‐functional molecule that can be used not only as a CDK2‐targeted fluorescent probe for bio‐imaging (λabs 338 nm, λems 443 nm) but also as a CDK2 targeted inhibitor for HeLa cells (IC 50: 0.5 μg/mL). At the sub cellular level, Ugi EML BLUE can selectively interact with the ATP binding sites of the activated CDK 2 to arrest the transfer of phosphate groups from its bound ATP to the serine and threonine residues of the target substrates involved in DNA transcription and replication initiated at the G1 cell cycle phase and which will lead to the inhibition of tumor growth.
A Metallogel Based on a Zwitterionic Spirocyclic Meisenheimer Complex: Sensing of Fluoride Ions in Water and Moisture Content in Organic Solvents
Authors: Mohar Mrittika
Published: May 2019

Design and synthesis of stimuli‐responsive materials are highly desired for various practical applications. For this purpose, a picric acid and N,N′‐dicyclohexylcarbodiimide based highly rigid zwitterionic spirocyclic Meisenheimer complex has been applied to produce a metallogel. The Meisenheimer complex does not undergo self‐gelation under any condition. But it forms a stable gel only with Fe3+ ion in a 2:1 ratio in chloroform. Interestingly, the Meisenheimer complex shows bright yellow emission under 366 nm UV light. But the Fe3+ based metallogel does not show any emission under UV irradiation. However, in the presence of fluoride contaminated water, the metallogel surface shows bright yellow emission while checking inside a UV chamber. Thus the non‐fluorescent metallogel was utilized as a sensor of aqueous fluoride ion. The sensor is able to detect aqueous fluoride down to 156 ppb concentration. Like the gel, the dried metallogel solution is also non‐fluorescent in different polar as well as nonpolar organic solvent. But the same solution shows bright yellow emission in the presence of water. The fluorescence intensity was found to increase with an increase in the percentage of water. In this way, the xerogel was utilized as a sensor of undesired water content present in different organic solvents which can detect moisture content with a minimum detection limit of 0.04% for dichloromethane.
Negotiating with Terrorists: The Costs of Compliance
Authors: Arin Kerim Peren , Feess Eberhard , Kuhlenkasper Torben , Reich Otto F. M.
Published: May 2019

It is often argued that negotiating with terrorists will encourage terrorist attacks. To date, corroborating empirical evidence is scarce. Using ITERATE data, we investigate the impact of conceding to terrorist demands on terror activity. We restrict attention to hostage events with clear‐cut demands from terrorists. Our sample period runs from 1978 to 2005 and comprises 1435 events in 125 countries. Estimating a flexible and dynamic Structured Additive Regression model, we find that the percentage of successfully negotiated events has a nonlinear effect on future terror intensity consistent with our simple theoretical model. More specifically, although moderate rates of negotiation increase the number of future terror events, higher negotiation rates tend to have the opposite effect. The estimated threshold is around 20%.
“Systems medicine” in the view of von Bertalanffy's “organismic biology” and systems theory
Authors: Tretter Felix
Published: May 2019

Currently, medicine is transforming towards molecular systems medicine (MSM), based on molecular systems biology (MSB). These approaches should be related to Ludwig von Bertalanffy's vision of “organismic” systems biology/medicine (OSB/OSM) and of general system theory (GST), which he created already in the 1930s. In this paper, on the basis of current diversity of knowledge in medicine, major differences between MSB/MSM and OSB/OSM are highlighted: MSB is based on biochemical high‐throughput technologies, sophisticated mathematical data analytical tools, and supercomputers for computation, whereas OSB is based on developmental biology and is concept and theory oriented. Metatheoretical considerations show that holistic but still reductive MSM cannot bridge the categorical molecule–cell difference, the mind–body difference, and the environment–organism gap by a consistent molecular and mechanistic theory of the organism. In contrast, the options of theoretical interlevel modelling with the help of simply structured but complexly functioning organ models are discussed here. As example, the neurochemical mobile of the brain is discussed. Consequently, a reconsideration of GST in medicine, targeting OSM, seems to be fruitful by linking MSM with a core concept of a systems pathology and with psychosocial and clinical medicine.
Epigenetic Priming of Human Pluripotent Stem Cell-Derived Cardiac Progenitor Cells Accelerates Cardiomyocyte Maturation
Authors: Biermann Mitch , Cai Wenxuan , Lang Di , Hermsen Jack , Profio Luke , Zhou Ying , Czirok Andras , Isai Dona G. , Napiwocki Brett N. , Rodriguez Adriana M. , Brown Matthew E. , Woon Marites T. , Shao Annie , Han Tianxiao , Park Donglim , Hacker Timothy A. , Crone Wendy C. , Burlingham William J. , Glukhov Alexey V. , Ge Ying , Kamp Timothy J.
Published: May 2019

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) exhibit a fetal phenotype that limits in vitro and therapeutic applications. Strategies to promote cardiomyocyte maturation have focused interventions on differentiated hPSC-CMs, but this study tests priming of early cardiac progenitor cells (CPCs) with polyinosinic-polycytidylic acid (pIC) to accelerate cardiomyocyte maturation. CPCs were differentiated from hPSCs using a monolayer differentiation protocol with defined small molecule Wnt temporal modulation, and pIC was added during the formation of early CPCs. pIC priming did not alter the expression of cell surface markers for CPCs (>80% KDR+/PDGFRα+), expression of common cardiac transcription factors, or final purity of differentiated hPSC-CMs (∼90%). However, CPC differentiation in basal medium revealed that pIC priming resulted in hPSC-CMs with enhanced maturity manifested by increased cell size, greater contractility, faster electrical upstrokes, increased oxidative metabolism, and more mature sarcomeric structure and composition. To investigate the mechanisms of CPC priming, RNAseq revealed that cardiac progenitor-stage pIC modulated early Notch signaling and cardiomyogenic transcriptional programs. Chromatin immunoprecipitation of CPCs showed that pIC treatment increased deposition of the H3K9ac activating epigenetic mark at core promoters of cardiac myofilament genes and the Notch ligand, JAG1. Inhibition of Notch signaling blocked the effects of pIC on differentiation and cardiomyocyte maturation. Furthermore, primed CPCs showed more robust formation of hPSC-CMs grafts when transplanted to the NSGW mouse kidney capsule. Overall, epigenetic modulation of CPCs with pIC accelerates cardiomyocyte maturation enabling basic research applications and potential therapeutic uses. Stem Cells  2019;37:910–923
A facile method to fabricate durable super‐hydrophobic cotton fabric
Authors: Li Junyu , Wu Xi , Jiang Peiqing , Li Linfeng , He Jiahao , Xu Weilin , Li Wenbin
Published: May 2019

This article presents the fabrication of super‐hydrophobic cotton fabric using titanium dioxide nanoparticles and tetraethyl orthosilicate, alongside control samples modified by 1H,1H,2H,2H‐perfluorooctyltriethoxysilane. The samples were analyzed using scanning electron microscopy and Fourier transform infrared spectrometry, and then, the water contact angles were measured. Moreover, the durability of the hydrophobic surface was examined by measuring the abrasion resistance and laundering durability. For the tetraethyl orthosilicate‐treated fabric, the water contact angle reached 150.3°, whereas that for the 1H,1H,2H,2H‐perfluorooctyltriethoxysilane‐treated fabric was 154.1°. After 300 abrasion cycles (or 40 min of laundering), the water contact angles of cotton fabrics treated with a 20% tetraethyl orthosilicate treatment solution dropped by 6.67% (or 2.86%). Therefore, hydrophobic cotton fabrics can be obtained via treatment with tetraethyl orthosilicate solution, which is more environmentally friendly than that obtained via fluorosilanes such as 1H,1H,2H,2H‐perfluorooctyltriethoxysilane. J. VINYL ADDIT. TECHNOL., 26:3–9, 2020. © 2019 Society of Plastics Engineers
Silica and diatomite fillers modified fluorine rubber composites treated by silane‐coupling agents
Authors: Wu Weili , Cong Songyan
Published: May 2019

The fluorine rubber nanocomposites were prepared by using the silane‐coupling agents treated silica and diatomite, in which 3‐amino propyltriethoxysilane (KH550), 3‐mercapto‐propyl trimethoxysilane (KH590), and bis‐(γ‐triethoxysilylpropyl)‐tetrasulfide (Si69) of the coupling agent were used as the filler modifiers to increase the compatibility between filler and fluorine rubber. The structure and morphology of the composites were investigated by Fourier transform infrared spectroscopy and scanning electron microscopy. The Tg and thermal stability of the composites were investigated by dynamic mechanical analysis and thermogravimetric analysis. The results showed that the best coupling agent was KH550 and 2 phr (parts per hundred rubber). The KH550‐modified compound filler was crosslinked with fluorine rubber, and the compatibility between filler and fluorine rubber was improved and further confirmed to improve the thermal properties of fluorine rubber with the KH550‐modified filler. J. VINYL ADDIT. TECHNOL., 26:55–61, 2020. © 2019 Society of Plastics Engineers
Hybrid Inorganic‐Organic Frameworks: Synthesis and Crystal Structures of RbFe(SO4)(C2O4)0.5·H2O and CsM(SO4)(C2O4)0.5·H2O (M = Mn, Fe)
Authors: Li Xiaofang , Wu Yuandong , Mei Dajiang , Doert Thomas
Published: May 2019

Three new alkali metal transition metal sulfate‐oxalates, RbFe(SO4)(C2O4)0.5·H2O and CsM(SO4)(C2O4)0.5·H2O (M = Mn, Fe) were prepared through hydrothermal reactions and characterized by single‐crystal X‐ray diffraction, solid state UV/Vis/NIR diffuse reflectance spectroscopy, infrared spectra, thermogravimetric analysis, and powder X‐ray diffraction. The title compounds all crystallize in the monoclinic space group P21/c (no. 14) with lattice parameters: a = 7.9193(5), b = 9.4907(6), c = 8.8090(6) Å, β = 95.180(2)°, Z = 4 for RbFe(SO4)(C2O4)0.5·H2O; a = 8.0654(11), b = 9.6103(13), c = 9.2189(13) Å, β = 94.564(4)°, Z = 4 for CsMn(SO4)(C2O4)0.5·H2O; and a = 7.9377(3), b = 9.5757(4), c = 9.1474(4) Å, β = 96.1040(10)°, Z = 4 for CsFe(SO4)(C2O4)0.5·H2O. All compounds exhibit three‐dimensional frameworks composed of [MO6] octahedra, [SO4]2– tetrahedra, and [C2O4]2– anions. The alkali cations are located in one‐dimensional tunnels.
Geometric aspects of holographic bit threads
Authors: Agón Cesar A. , de Boer Jan , Pedraza Juan F.
Published: May 2019

Abstract

We revisit the recent reformulation of the holographic prescription to compute entanglement entropy in terms of a convex optimization problem, introduced by Freedman and Headrick. According to it, the holographic entanglement entropy associated to a boundary region is given by the maximum flux of a bounded, divergenceless vector field, through the corresponding region. Our work leads to two main results: (i) We present a general algorithm that allows the construction of explicit thread configurations in cases where the minimal surface is known. We illustrate the method with simple examples: spheres and strips in vacuum AdS, and strips in a black brane geometry. Studying more generic bulk metrics, we uncover a sufficient set of conditions on the geometry and matter fields that must hold to be able to use our prescription. (ii) Based on the nesting property of holographic entanglement entropy, we develop a method to construct bit threads that maximize the flux through a given bulk region. As a byproduct, we are able to construct more general thread configurations by combining (i) and (ii) in multiple patches. We apply our methods to study bit threads which simultaneously compute the entanglement entropy and the entanglement of purification of mixed states and comment on their interpretation in terms of entanglement distillation. We also consider the case of disjoint regions for which we can explicitly construct the so-called multi-commodity flows and show that the monogamy property of mutual information can be easily illustrated from our constructions.
Efficient verification of concurrent systems using local-analysis-based approximations and SAT solving
Authors: Antonino Pedro , Gibson-Robinson Thomas , Roscoe A. W.
Published: May 2019

This work develops a type of local analysis that can prove concurrent systems deadlock free. As opposed to examining the overall behaviour of a system, local analysis consists of examining the behaviour of small parts of the system to yield a given property. We analyse pairs of interacting components to approximate system reachability and propose a new sound but incomplete/approximate framework that checks deadlock and local-deadlock freedom. By replacing exact reachability by this approximation, it looks for deadlock (or local-deadlock) candidates, namely, blocked (locally-blocked) system states that lie within our approximation. This characterisation improves on the precision of current approximate techniques. In particular, it can tackle non-hereditary deadlock-free systems, namely, deadlock-free systems that have a deadlocking subsystem. These are neglected by most approximate techniques. Furthermore, we demonstrate how SAT checkers can be used to efficiently implement our framework, which, typically, scales better than current techniques for deadlock-freedom analysis. This is demonstrated by a series of practical experiments.
Goals and targets: a developmental puzzle about sensitivity to others’ actions
Authors: Butterfill Stephen A.
Published: May 2019

Sensitivity to others’ actions is essential for social animals like humans and a fundamental requirement for any kind of social cognition. Unsurprisingly, it is present in humans from early in the first year of life. But what processes underpin infants’ sensitivity to others’ actions? Any attempt to answer this question must solve twin puzzles about the development of goal tracking. Why does some, but not all, of infants’ goal tracking appear to be limited by their abilities to represent the observed action motorically at the time it occurs? And why does their sensitivity to action sometimes manifest itself differently in dishabituation, pupil dilation and anticipatory looking? Solving these twin puzzles is critical for understanding humans’ earliest sensitivity to others’ actions. After introducing the puzzles, this paper argues that solving them may require identifying multiple, distinct processes for tracking the targets and goals of actions.
Decay Dynamics of Localized Surface Plasmons: Damping of Coherences and Populations of the Oscillatory Plasmon Modes
Authors: Kolwas Krystyna
Published: May 2019

Properties of plasmonic materials are associated with surface plasmons—the electromagnetic excitations coupled to coherent electron charge density oscillations on a metal/dielectric interface. Although decay of such oscillations cannot be avoided, there are prospects for controlling plasmon damping dynamics. In spherical metal nanoparticles (MNPs), the basic properties of localized surface plasmons (LSPs) can be controlled with their radius. The present paper handles the link between the size-dependent description of LSP properties derived from the dispersion relation based on Maxwell’s equations and the quantum picture in which MNPs are treated as “quasi-particles.” Such picture, based on the reduced density matrix of quantum open systems ruled by the master equation in the Lindblad form, enables to distinguish between damping processes of populations and coherences of multipolar plasmon oscillatory states and to establish the intrinsic relations between the rates of these processes, independently of the size of MNP. The impact of the radiative and the nonradiative energy dissipation channels is discussed.
A model of NSCLC microenvironment predicts optimal receptor targets
Authors: Han Chuang , Wu Yu
Published: May 2019

Background

Tumor microenvironment plays an essential role in the growth of malignancy. Understanding how tumor cells co‐evolve with tumor‐associated immune cells and stromal cells is important for tumor treatment.

Methods

In this paper, we propose a logistic population dynamics model for quantifying the intercellular signaling network in non‐small‐cell lung cancer (NSCLC). The model describes the evolutionary dynamics of cells and signaling proteins and was used to predict effective receptor targets through combination strategy analysis. Then, we optimized a multi‐target strategy analysis algorithm that was verified by applying it to virtual patients with heterogeneous conditions. Furthermore, to deal with acquired resistance which was commonly observed in patients with NSCLC, we proposed a novel targeting strategy — tracking targeted therapy, to optimize the treatment by improving the therapeutic strategy periodically.

Results

The synergistic effect when inhibiting multiple signaling pathways may help significantly retard carcinogenic processes associated with disease progression, compared with suppression of a single signaling pathway. While traditional treatment (surgery, radiotherapy and chemotherapy) tends to attack tumor cells directly, the multi‐target therapy we suggested here is aimed to inhibit the development of tumor by emasculating the relative competitive advantages of tumor cells and promoting that of normal cells.

Conclusion

The combination of traditional and targeted therapy, as an interesting experiment, was significantly more effective in treatment of virtual patients due to a clear complementary relationship between the two therapeutic schemes.