bluuebunny/crossref_metadata_2025 huggingface dataset:
Complexity and evolution of knowledge boundaries in an interdisciplinary research project
Authors: Thumbumrung Titima , Vasconcelos Ana , Cox Andrew
Published: August 2022

This paper aims to understand how and why knowledge boundaries occur, change, and evolve throughout the life‐cycle of interdisciplinary research projects, how they are experienced by different actors, and what strategies they deploy to overcome these boundaries. The study took a case study approach focusing on an interdisciplinary research project for the development of computerised tomography and digital X‐ray scanners in a governmental research organisation in Thailand. A multi‐method qualitative approach, involving semi‐structured interviews, participative observation, and artefact and document analysis, was adopted. Data was analysed through thematic analysis. The findings suggest that knowledge management is more complex and difficult than portrayed in previous studies because of the following: (1) knowledge boundaries evolve and exhibit different emphases at distinct stages of the project; (2) boundaries do not stem only from differences in knowledge across different organisational actors, but, equally importantly, due to the lack of awareness that these differences exist; (3) different organisational actors experience diverse types of knowledge boundary types when faced within the same situation; and (4) context, in terms of external pressures driving the project and influencing its direction, plays an important role in boundary construction and boundary‐spanning mechanisms. This paper presents a novel framework for conceptualising how and why knowledge boundaries evolve throughout an interdisciplinary research project, how these changes are experienced by different participating actors, and what boundary‐spanning mechanisms for bridging them are developed by them. It demonstrates that these changes are often shaped by external drivers that shape the development of the project.
Dual‐Functional Nonmetallic Plasmonic Hybrids with Three‐Order Enhanced Upconversion Emission and Photothermal Bio‐Therapy
Authors: Li Juan , Liu Lu , Chen Xueqin , Lu Changhai , Zhang Haipeng , Li Baojun , Xue Can , Lou Zaizhu
Published: August 2022

Plasmonic semiconductor nanoparticles (NPs) with wide‐range tailorable localized surface plasmon resonance (LSPR) hold exciting prospects on optical signal amplification. In this work, by precisely controlling oxygen vacancies around W atoms, plasmonic bismuth tungstate Bi2WO6 (BWO) nanosheets are constructed to enhance emission of Yb3+/Er3+ co‐doped NaYF4 upconversion nanoparticles (UCNPs). In the optimal conditions, the UCNPs/BWO‐2 hybrids exhibit over three‐order (1260‐fold) enhancement selectively on the 520 nm emission owing to the strong LSPR‐induced electrical field and photothermal effect. Moreover, it is found that the highly efficient emission of UCNPs/BWO‐2 allows it to act as a thermometer to monitor the real‐time local temperature with high absolute sensitivity of 5.8 × 10−3 K−1 in wide temperature range (up to 990 K). For proof‐of‐concept, the dual functions of plasmonic UCNPs/BWO‐2 hybrids on bioimaging and photothermal therapy for cancer cells are demonstrated that can be completely killed within 5 min under 980 nm irradiation. As far as it is known, this work reaches a new level on UCNPs emission enhancement by plasmonic semiconductor, exceeding most plasmonic metals.
FFF 3D Printing of Small Porous Structures from Polymer Compounds Using the Ultimaker 3
Authors: Ernst Matthias F. , Maletzko Annabelle , Baumann Sascha , Baumann Nils , Hübner Christof , Höhne Carl‐Christoph
Published: August 2022

Additive manufacturing offers a great potential for the production of objects with a tailor‐made inner structure especially in combination with material development in the field of polymer compounds. However, the design possibilities for the inner structure depend on printing resolution, accuracy, and reproducibility. The quality of small filigree objects printed by additive manufacturing processes for polymer materials like fused filament fabrication (FFF) depends on the polymer material itself as well as on the processing parameters in the additive manufacturing technology used. Here, the production of small porous structures by FFF with an Ultimaker 3 is analyzed using polylactic acid (PLA) as well as polymer compounds of PLA containing carbon nanotubes (CNTs) and polyvinyl alcohol (PVA) containing titanium dioxide (TiO2). The influences of the calibration of the building plate, the heights of the 1st, 2nd, and 3rd layers, and of particulate additives on the printing behavior of the polymer compound, and hence the resulting accuracy of the width of single printed lines, are studied. Additionally, the printing of lattice‐like scaffold structures using PLA/CNT forming the structure and PVA/TiO2 as soluble support structure is described.
Affinity selection‐mass spectrometry in the discovery of anti‐SARS‐CoV‐2 compounds
Authors: van Breemen Richard B. , Muchiri Ruth N.
Published: August 2022

Small molecule therapeutic agents are needed to treat or prevent infections by severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), which is the cause of the COVID‐19 pandemic. To expedite the discovery of lead compounds for development, assays have been developed based on affinity selection‐mass spectrometry (AS‐MS), which enables the rapid screening of mixtures such as combinatorial libraries and extracts of botanicals or other sources of natural products. AS‐MS assays have been used to find ligands to the SARS‐CoV‐2 spike protein for inhibition of cell entry as well as to the 3‐chymotrypsin‐like cysteine protease (3CLpro) and the RNA‐dependent RNA polymerase complex constituent Nsp9, which are targets for inhibition of viral replication. The AS‐MS approach of magnetic microbead affinity selection screening has been used to discover high‐affinity peptide ligands to the spike protein as well as the hemp cannabinoids cannabidiolic acid and cannabigerolic acid, which can prevent cell infection by SARS‐CoV‐2. Another AS‐MS method, native mass spectrometry, has been used to discover that the flavonoids baicalein, scutellarein, and ganhuangenin, can inhibit the SARS‐CoV‐2 protease 3CLpro. Native mass spectrometry has also been used to find an ent‐kaurane natural product, oridonin, that can bind to the viral protein Nsp9 and interfere with RNA replication. These natural lead compounds are under investigation for the development of therapeutic agents to prevent or treat SARS‐CoV‐2 infection.
Characterization of physical vapor deposited coating on acrylonitrile‐butadiene‐styrene and polycarbonate substrates
Authors: Toroslu A.G. , Tekiner Z. , Mert F.
Published: August 2022

In this study, acrylonitrile‐butadiene‐styrene and polycarbonate substrates plastics were coated with aluminum by physical vapor deposition method in order to determine which one is a better choice for outdoor reflector technology. This investigation has been done by applying the coating on a reflector that is already been used in the lighting industry. Scraping test, caustic soda and caustic potash test, reflection efficiency performance test and surface roughness test methods were used to determine the selection. Coatings on acrylonitrile‐butadiene‐styrene and polycarbonate plastic materials were characterized by scanning electron microscopy and energy dispersive x‐ray spectrometry. Although acrylonitrile‐butadiene‐styrene plastic material is easier for injection molding and cheaper than polycarbonate material, the results showed that polycarbonate plastic material is more efficient than acrylonitrile‐butadiene‐styrene plastic material, especially in terms of surface roughness and reflection efficiency.
Effect of cooling system and forming structure on grain sizes and mechanical properties of S43CMnV for non‐quenched and tempered steel crankshaft
Authors: Liu F. , Shen N.R. , Zhou L. , Huang B. , Yue G. , Lin S.Y. , Luo Y.C. , Mao X.F. , Du J.
Published: August 2022

Taking the given S43CMnV non‐quenched and tempered steel multi‐cylinder (3‐cylinder and 4‐cylinder) crankshaft as the research object, the intrinsic relationship between the forging process, temperature controlled cooling process of 3‐cylinder crankshaft and the global‐local grain evolution process was analyzed by Deform‐3D software. Meanwhile, the influence relationship between average grain sizes and comprehensive mechanical properties of the 3‐cylinder and 4‐cylinder crankshaft was compared and analyzed in details. The results show that for the 3‐cylinder crankshaft, the larger cooling rates can achieve the smaller grain sizes. When the temperature controlled cooling rate is 60 °C/min, the average grain sizes of the crankshaft pin bearing, main bearing and flange end are 61.5 μm, 96.9 μm and 70.7 μm respectively, which meets the requirements of production process (approximately 127 μm). Wherein, the grain sizes and mechanical properties of the 4‐cylinder crankshaft are better than those of the 3‐cylinder crankshaft, and the after‐forging elongation of the 4‐cylinder crankshaft can reach at approximately 16.6 %. Furthermore, the grain sizes evolution of 3‐cylinder crankshaft obtained by numerical simulations are basically consistent with the experimental grain size results, and it is feasible to predict and control the grain sizes’ evolution and mechanical properties of the crankshaft hot forging by using Deform‐3D.
Kaiser MH clinicians may strike over lack of patient care
Authors: Canady Valerie A.
Published: August 2022

Enough is enough. That's no doubt the thinking behind the more than 2,000 unionized California‐based psychologists, therapists, chemical dependency counselors and social workers who've demanded that Kaiser Permanente provide urgently needed mental health services to its patients.
The increasingly pivotal role of supervisors and mentors
Authors: Greaney Thomas M.
Published: August 2022

The landscape of delivering critically needed mental health counseling and other services has shifted dramatically during the COVID‐19 pandemic. Some see it as an earthquake, forever changing the topography of mental health service delivery. In fact, the acuity and frequency of mental health crises precipitated by isolation and recurrence of substance use during the COVID‐19 national health crisis resulted in 30% of U.S. adults reporting “symptoms consistent with depression or anxiety since April 2020.” (“Telehealth has played an outsized role meeting mental health needs during the COVID‐19 pandemic,” https://www.KFF.org, March 15, 2022). Telehealth was used in an attempt to bridge the gap of client needs during stay‐at‐home periods of isolation.
Selection of deep or superficial recipient vein in lower extremity reconstruction using free flap: A systematic review and meta‐analysis
Authors: Shimbo Keisuke , Kawamoto Haruka , Koshima Isao
Published: August 2022

Background

Free flap surgeries are useful procedures for lower‐extremity reconstruction. Recipient vein selection for anastomosis is important to avoid venous congestion and thrombosis. Although deep or superficial venous system can be used as a recipient vein site, there is a lack of consensus on which system would be superior to avoid postoperative complications. This systematic review and meta‐analysis aimed to assess the differences in outcomes between deep and superficial vein anastomosis for lower‐extremity free flap reconstruction.

Methods

The PubMed, Scopus, Web of Science, and Cochrane Library medical databases were systematically searched from inception to April 2022, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐analyses guidelines. A comparative meta‐analysis was conducted on studies of deep and superficial venous system anastomosis outcomes, comprising vascular thrombosis, reoperation, complete flap necrosis, and any flap necrosis. The fixed‐effects meta‐analysis model was used when low heterogeneity (I2 < 50%) was present.

Results

Six studies with 789 flaps were included in the analysis and qualitative and quantitative syntheses. The rate of vascular thrombosis (8.2% vs. 15.1%; p = .005) was significantly lower for flaps involving deep vein anastomosis than for those involving superficial vein anastomosis. The rate of reoperation after deep vein anastomosis was lower than that after superficial vein anastomosis, with no statistically significant difference (9.0% vs. 14.7%; p = .06). There were no significant differences in the rates of complete (2.5% vs. 2.0%; p = .90) or any flap necrosis (7.0% vs. 9.8%; p = .20).

Conclusion

Deep vein anastomosis might be recommended for avoiding vascular thrombosis.
A probabilistic data assimilation framework to reconstruct finite element error fields from sparse error estimates: Application to sub‐modeling
Authors: Paul Rouse James , Kerfriden Pierre , Hamadi Maxime
Published: August 2022

The present work proposes a computational approach that recovers full finite element error fields from a small number of estimates of errors in scalar quantities of interest. The approach is weakly intrusive and is motivated by large scale industrial applications wherein modifying the finite element models is undesirable and multiple regions of interest may exist in a single model. Error estimates are developed using a Zhu‐Zienkiewicz estimator coupled with the adjoint methodology to deliver goal‐oriented results. A Bayesian probabilistic estimation framework is deployed for full field estimation. An adaptive, radial basis function based reduced order modeling strategy is implemented to reduce the cost of calculating the posterior. The Bayesian reconstruction approach, accelerated by the proposed model reduction technology, is shown to yield good probabilistic estimates of full error fields, with a computational complexity that is acceptable compared to the evaluation of the goal‐oriented error estimates. The novelty of the work is that a set of computed error estimates are considered as partial observations of an underlying error field, which is to be recovered. Future improvements of the method include the optimal selection of goal‐oriented error measures to be acquired prior to the error field reconstruction.
Validation of energy expenditure and macronutrient oxidation measured by two new whole‐room indirect calorimeters
Authors: Dörner Rebecca , Hägele Franziska A. , Koop Jana , Rising Russell , Foerster Thomas , Olsen Thomas , Hasler Mario , Müller Manfred J. , Bosy‐Westphal Anja
Published: August 2022

Objective

The aim of this study was to validate two new whole‐room indirfect calorimeters according to Room Indirect Calorimetry Operating and Reporting Standards (RICORS 1.0).

Methods

For technical validation, 16 propane combustion tests were performed to determine accuracy and precision of energy expenditure (EE) and ventilation rates of oxygen (VO2), carbon dioxide (VCO2), and respiratory exchange ratio (VCO2/VO2). For biological validation, eight participants (mean [SD], age 24.1 [2.5] years; BMI 24.3 [3.1] kg/m2) underwent four 24‐hour protocols under highly standardized conditions: (1) isocaloric sedentary, (2) fasting sedentary, (3) isocaloric active, and (4) fasting active. Reliability (coefficients of variation [CV]) and minimal detectable changes (MDC) were calculated for 24‐hour EE, sleeping metabolic rate (SMR), physical activity energy expenditure (PAEE), thermic effect of food (TEF), and macronutrient oxidation rates.

Results

Technical validation showed high reliability and recovery rates for VO2 (0.75% and 100.8%, respectively), VCO2 (0.49% and 100.6%), and EE (0.54% and 98.2%). Biological validation revealed CV and MDC for active conditions of 1.4% and 4.3% for 24‐hour EE, 1.7% and 5.9% for SMR, and 30.2% and 38.4% for TEF, as well as 5.8% and 10.5% for PAEE, respectively. Mean CV and MDC for macronutrient oxidation rates were 9.9% and 22.9%, respectively.

Conclusions

The precision of 24‐hour EE and SMR was high, whereas it was lower for PAEE and poor for TEF.
Pulmonary function in children and adolescents with sickle cell disease after nonmyeloablative hematopoietic cell transplantation
Authors: Monagel Dania A. , Guilcher Gregory M. T. , Nettel‐Aguirre Alberto , Bendiak Glenda N.
Published: August 2022

Background

Pulmonary complications are common in sickle cell disease (SCD). The use of standard myeloablative conditioning regimens may increase the risk of lung injury. We report serial pulmonary function testing (PFT) outcomes in children with SCD who underwent a matched‐sibling donor hematopoietic cell transplantation (HCT) using nonmyeloablative (NMA) protocol.

Methods

This is a retrospective chart review describing pulmonary outcomes in pediatric patients post HCT. The conditioning regimen consisted of alemtuzumab and a single fraction of 300 cGy of total body irradiation (TBI), and sirolimus for graft‐versus‐host disease (GVHD) prophylaxis. Serial PFT testing was performed pre and post HCT. The evaluated pulmonary measures included: forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), FEV1/FVC, and forced expiratory flow (FEF25‐75).

Results

Twelve subjects were included in the analysis. All had HbSS genotype, and five of the 12 patients had one or more episodes of acute chest syndrome prior to HCT. Serial PFT measures were completed per patient. No patient was diagnosed with chronic GVHD of any organ post HCT. The baseline median FVC, FEV1, FEV1/FVC, and FEF25‐75 were within the normal range and remained relatively unchanged post HCT. A linear mixed effects model, adjusting for gender and time from HCT, suggested no significant relationship between HCT and PFT parameters, including FVC, FEV1, and FEV1/FVC. Interestingly, the FEF25‐75 results exhibited a shift in the means post HCT (pre‐HCT 86.2% predicted and post‐HCT 93.05% predicted, p‐value = .018).

Conclusion

Our study suggests that HCT in children with SCD may prevent the anticipated decline in pulmonary function over time.
Ethical issues associated with prenatal screening using non‐invasive prenatal testing for sex chromosome aneuploidy
Authors: Johnston Molly , Warton Chanelle , Pertile Mark D. , Taylor‐Sands Michelle , Delatycki Martin B. , Hui Lisa , Savulescu Julian , Mills Catherine
Published: August 2022

Prenatal screening for sex chromosome aneuploidies (SCAs) is increasingly available through expanded non‐invasive prenatal testing (NIPT). NIPT for SCAs raises complex ethical issues for clinical providers, prospective parents and future children. This paper discusses the ethical issues that arise around NIPT for SCAs and current guidelines and protocols for management. The first section outlines current practice and the limitations of NIPT for SCAs. It then outlines key guidelines before discussing the ethical issues raised by this use of NIPT. We conclude that while screening for SCAs should be made available for people seeking to use NIPT, its implementation requires careful consideration of what, when and how information is provided to users.
Temporal shifts in safety and efficacy profile of mycophenolate mofetil 2 g versus 3 g daily early after heart transplantation
Authors: Braghieri Lorenzo , Jennings Douglas L. , Bohn Bruno , Habal Marlena , Pinsino Alberto , Mondellini Giulio M. , Ladanyi Annamaria , Latif Farhana , Clerkin Kevin , Restaino Susan , Kurlansky Paul , Takeda Koji , Naka Yoshifumi , Demmer Ryan T. , Sayer Gabriel T. , Uriel Nir , Colombo Paolo C. , Yuzefpolskaya Melana
Published: August 2022

Study Objective

Mycophenolate mofetil (MMF) is the gold‐standard immunosuppressive agent in heart transplantation (HT), but dose‐dependent toxicities (e.g., neutropenia) are frequent. Gut bacteria β‐d‐glucuronidases (GUS) modulate MMF bioavailability, and changes in the intestinal flora may influence the pharmacokinetics of MMF. The objective of this study was to evaluate the safety and efficacy of MMF 1.5 g every 12 h (q12) [high‐dose, HD] versus 1 g q12 [low‐dose, LD] and explore the association between neutropenia and GUS.

Measurements

We compared the incidence of acute cellular rejection (ACR) and neutropenia during the first 6 months post‐HT. The association between neutropenia and GUS was investigated in an exploratory analysis on a subset of patients with prospectively collected stool data. Stool samples were analyzed using 16S rRNA sequencing.

Main Results

A total of 168 patients (120 MMF‐HD, 48 MMF‐LD; mean age 55.7 years, 79% male) were studied. Neutropenia occurred in 38.6% of patients at a median of 106 [64–143] days. Freedom from neutropenia was lower in MMF‐HD compared with MMF‐LD (57% vs. 73%, p = 0.03). ACR (≥1R/1B) occurred in 37.5% of patients at a median of 20 [10–96] days, while high‐grade ACR (≥2R/3A) occurred in 11.3% at a median of 14 [9–89] days. Freedom from ACR was similar between groups. MMF‐LD was associated with more high‐grade ACR (hazard ratio [HR] 3.47, 95% confidence interval [CI] 1.09–11.08, p = 0.03) during the first month, but less neutropenia (HR 0.54, 95% CI 0.29–1.00, p = 0.05) between 1 and 6 months. GUS‐producing bacteria were more abundant in neutropenic patients.

Conclusions

MMF‐LD was associated with higher rates of early high‐grade ACR and lower rates of later neutropenia. Further studies are warranted to test whether temporal MMF dose adjustments and gut microbial composition could improve clinical outcomes post‐HT.
A mutant allele of the flowering promoting factor 1 gene at the tomato BRACHYTIC locus reduces plant height with high quality fruit
Authors: Lee Man Bo , Shekasteband Reza , Hutton Samuel F. , Lee Tong Geon
Published: August 2022

Reduced plant height due to shortened stems is beneficial for improving crop yield potential, better resilience to biotic/abiotic stresses, and rapid crop producer adoption of the agronomic and management practices. Breeding tomato plants with a reduced height, however, poses a particular challenge because this trait is often associated with a significant fruit size (weight) reduction. The tomato BRACHYTIC (BR) locus controls plant height. Genetic mapping and genome assembly revealed three flowering promoting factor 1 (FPF1) genes located within the BR mapping interval, and a complete coding sequence deletion of the telomere proximal FPF1 (Solyc01g066980) was found in the br allele but not in BR. The knock‐out of Solyc01g066980 in BR large‐fruited fresh‐market tomato reduced the height and fruit yield, but the ability to produce large size fruits was retained. However, concurrent yield evaluation of a pair of sister lines with or without the br allele revealed that artificial selection contributes to commercially acceptable yield potential in br tomatoes. A network analysis of gene‐expression patterns across genotypes, tissues, and the gibberellic acid (GA) treatment revealed that member(s) of the FPF1 family may play a role in the suppression of the GA biosynthesis in roots and provided a framework for identifying the responsible molecular signaling pathways in br‐mediated phenotypic changes. Lastly, mutations of br homologs also resulted in reduced height. These results shed light on the genetic and physiological mechanisms by which the br allele alters tomato architecture.
Targeted mutagenesis of StISAC stabilizes the production of anthocyanins in potato cell culture
Authors: D'Amelia Vincenzo , Staiti Annalisa , D'Orso Fabio , Maisto Maria , Piccolo Vincenzo , Aversano Riccardo , Carputo Domenico
Published: August 2022

To increase the production of decorated anthocyanins in potato cell cultures, we knocked out a novel potato gene, named Inducer Silencing of Anthocyanins in Cell culture (StISAC), using CRISPR‐Cas9 editing. Our results provided evidence that mutant cell lines doubled the accumulation level of anthocyanins biosynthesized. Moreover, the production of these important pigments was stabilized over time. Our study overcame important challenges in the efficient biotechnological production of these valuable pigments and reported the function of a novel anthocyanin biosynthesis repressor gene.
Registration of ‘ND VitPro’ hard red spring wheat
Authors: Green Andrew J. , Mergoum Mohamed , Frohberg Richard , Underdahl Jesse , Horsley Richard , Walz Adam , Simsek Senay , Otteson Brian , Heilman‐Morales Ana Maria , Friskop Andrew , Ransom Joel , Rickertsen John , Ostlie Mike , Schatz Blaine , Hanson Bryan , Eriksmoen Eric , Pradhan Gautam , Martin Glenn , Rasmussen Jack , Zhong Shaobin , Friesen Tim , Rouse Matthew , Jin Yue , Chao Shiaoman , Acevedo Maricelis
Published: August 2022

‘ND VitPro’ (Reg. no. CV‐1194, PI 682660) is a hard red spring wheat (HRSW, Triticum aestivum L.) developed at North Dakota State University and released by the North Dakota Agricultural Experiment Station in 2017. It was tested as experimental line ND825 and released because of improved straw strength as well as strong disease resistance and end‐use quality. ND VitPro is moderately resistant to stem rust, leaf rust, and Fusarium head blight. The name ND VitPro was chosen due to its high vitreous kernel percentage and high grain protein.
Corona‐aged performance of nano‐filled HTV silicone rubber
Authors: Saleem Muhammad Z. , Akbar Mohammad , Alam Shahid
Published: August 2022

To develop compact and relatively low maintenance demanding high voltage transmission systems, polymeric insulators are widely replacing traditionally used insulators for the past several decades. Further efforts focusing on enhancing their antiaging performance by adding fillers to increase the reliability of power systems are being made through extensive research globally. Among the causes of degradation, corona discharge is considered of great concern and needs to be investigated at length. Toward that end, several types of high‐temperature vulcanized silicone rubber (HTV‐SiR) were reinforced with varying quantities of nano‐sized boron nitride (BN) and silicon carbide (SiC) fillers are evaluated in this study. Test samples with different formulations are fabricated and exposed to alternating current (AC) corona discharge for a duration of 72 h. Thereafter, the induced modifications in their surface characteristics and bulk properties are assessed using several diagnostic and complementary techniques involving measurements of partial discharge and volume current, scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and Fourier transform infrared (FTIR) spectroscopy. The volume current is recorded using a standardized three‐electrode system at different levels of the test voltage and ambient temperature in an attempt to evaluate its dependence on the electric field and temperature. As a result of the conducted study and allied analysis, it is reported that the damaging impact of corona retards more in the case of loading HTV‐SiR with nano‐sized particles of BN as compared to SiC. The obtained FTIR spectra demonstrate an increase in the transmittance intensity of principal peaks in the aged samples, being higher in the unfilled SiR than its filled counterparts. It is further revealed that exposure of the studied samples to corona discharge elevates their volume current possibly due to charge injection and space charge effect, particularly at higher temperatures and strong electric field.
Insight into the structural basis of the dual inhibitory mode of Lima bean (Phaseolus lunatus) serine protease inhibitor
Authors: Ahmad Malik Shoaib , Akbar Zeeshan , Choudhary Muhammad Iqbal
Published: August 2022

Bovine pancreatic trypsin was crystallized, in‐complex with Lima bean trypsin inhibitor (LBTI) (Phaseolus lunatus L.), in the form of a ternary complex. LBTI is a Bowman–Birk‐type bifunctional serine protease inhibitor, which has two independent inhibitory loops. Both of the loops can inhibit trypsin, however, only the hydrophobic loop is specific for inhibiting chymotrypsin. The structure of trypsin incomplex with the LBTI has been solved and refined at 2.25 Å resolution, in the space group P41, with Rwork/Rfree values of 18.1/23.3. The two binding sites of LBTI differ in only two amino acids. Lysine and leucine are the key residues of the two different binding loops positioned at the P1, and involved in binding the S1 binding site of trypsin. The asymmetric unit cell contains two molecules of trypsin and one molecule of LBTI. The key interactions include hydrogen bonds between LBTI and active site residues of trypsin. The 3D structure of the enzyme–inhibitor complex provided details insight into the trypsin inhibition by LBTI. To the best of our knowledge, this is the first report on the structure of trypsin incomplex with LBTI.
Characterization of TR‐107, a novel chemical activator of the human mitochondrial protease ClpP
Authors: Fennell Emily M. J. , Aponte‐Collazo Lucas J. , Wynn Joshua D. , Drizyte‐Miller Kristina , Leung Elisa , Greer Yoshimi Endo , Graves Paul R. , Iwanowicz Andrew A. , Ashamalla Hani , Holmuhamedov Ekhson , Lang Henk , Karanewsky Donald S. , Der Channing J. , Houry Walid A. , Lipkowitz Stanley , Iwanowicz Edwin J. , Graves Lee M.
Published: August 2022

We recently described the identification of a new class of small‐molecule activators of the mitochondrial protease ClpP. These compounds synthesized by Madera Therapeutics showed increased potency of cancer growth inhibition over the related compound ONC201. In this study, we describe chemical optimization and characterization of the next generation of highly potent and selective small‐molecule ClpP activators (TR compounds) and demonstrate their efficacy against breast cancer models in vitro and in vivo. We selected one compound (TR‐107) with excellent potency, specificity, and drug‐like properties for further evaluation. TR‐107 showed ClpP‐dependent growth inhibition in the low nanomolar range that was equipotent to paclitaxel in triple‐negative breast cancer (TNBC) cell models. TR‐107 also reduced specific mitochondrial proteins, including OXPHOS and TCA cycle components, in a time‐, dose‐, and ClpP‐dependent manner. Seahorse XF analysis and glucose deprivation experiments confirmed the inactivation of OXPHOS and increased dependence on glycolysis following TR‐107 exposure. The pharmacokinetic properties of TR‐107 were compared with other known ClpP activators including ONC201 and ONC212. TR‐107 displayed excellent exposure and serum t1/2 after oral administration. Using human TNBC MDA‐MB‐231 xenografts, the antitumor response to TR‐107 was investigated. Oral administration of TR‐107 resulted in a reduction in tumor volume and extension of survival in the treated compared with vehicle control mice. ClpP activation in vivo was validated by immunoblotting for TFAM and other mitochondrial proteins. In summary, we describe the identification of highly potent new ClpP agonists with improved efficacy against TNBC, through targeted inactivation of OXPHOS and disruption of mitochondrial metabolism.
Process‐oriented evaluation of the oversea AROME configuration: Focus on the representation of cloud organisation
Authors: Beucher Florent , Couvreux Fleur , Bouniol Dominique , Faure Ghislain , Favot Florence , Dauhut Thibaut , Ayet Alex
Published: August 2022

This study evaluates the ability of the French convection‐permitting model AROME‐OM to represent shallow cumulus and their main organisations for boreal winter conditions in the North Atlantic trades. It uses a set of three winter seasons (January–February, 2018–2020) of high‐resolution (1.3 and 2.5 km) simulations over the Caribbean domain (9.7–22.9°N, 75.3–51.7°W). The model is assessed against soundings at Grantley Adams Airport and remote‐sensing observations at a site located on the east coast of Barbados which is representative of downwind trade regimes. The thermodynamic environment of the model fits the observations overall but the boundary layer is slightly too deep, resulting in a weak cold and dry bias. Both model and observations clearly exhibit (a) a double peak of cloud fraction, a first peak near the cloud base and a second one near the cloud top and (b) a larger variance in cloudiness near the top of the deepest cumuli, at around 2 km, with a higher sensitivity to the environment. We then take advantage of the EUREC4A field campaign which took place in January–February 2020 to assess the ability of the model to reproduce the four main mesoscale patterns and to characterize the air masses in which they develop. All the observations confirm the capacity of the model to predict the different mesoscale organizations and their associated environment.
Global position tracking control of PMSM servo system via internal model approach and experimental validations
Authors: Ping Zhaowu , Jia Yingjie , Li Yaoyi , Huang Yunzhi , Wang Hai , Lu Jun‐Guo
Published: August 2022

In practical engineering, load torque disturbance and parameter uncertainties are two important factors, which may deteriorate the tracking accuracy of permanent magnet synchronous motor (PMSM) servo system. Therefore, its global position tracking control problem is a challenging task when the load torque disturbance is time‐varying and the motor parameters are unknown. In this article, an internal model controller based on global robust output regulation (GROR) theory is proposed to achieve this control objective. In particular, we first formulate the global position tracking control problem as a GROR problem. Then, the GROR problem is converted into a global robust stabilization problem of an augmented system by constructing an appropriate internal model. Finally, we can stabilize the augmented system by a global stabilization controller instead of local stabilization controller used in the recent work, which guarantees global position tracking and disturbance rejection of PMSM servo system. The excellent position tracking performance of our design is demonstrated by both simulation and experimental results.
High‐Performance Natural Graphite Anode for Lithium‐Ion Batteries: Using TiO2 as an Additive
Authors: Babaiee Mohsen , Baktashian Shaghayegh , Zarei‐Jelyani Mohammad , Eqra Rahim , Gholami Mehrdad
Published: August 2022

In this study, an attempt has been made to improve the performance of natural graphite anode using TiO2 nanoparticles additive. In this method, high‐performance electrodes have been achieved by addition of TiO2 nanoparticles to base graphite active material, which is able to offer supplementary effects. TiO2 emulsions with different concentrations of 10 %, 20 %, and 100 % are applied to prepare the binder solvent. The graphite anode made with 10 % concentration of TiO2 emulsion (NG−T10) shows the best performance in comparison with other samples. The Nano‐scale images of the scanning electron microscope (SEM) affirm the existence of a uniform coating on the surface of the natural graphite particles for the NG−T10 electrode. Energy‐dispersive X‐ray (EDX) spectroscopy on the NG−T10 sample clearly indicates the Ti element signal. According to atomic force microscopy (AFM) images, an increment in surface roughness can provide a more effective surface and improve wettability, resulting in better electrochemical performance of NG−T10. The charge‐discharge test of the NG−T10 half‐cell represents an excellent cycle performance without any capacity degradation during 100 cycles at 0.5 C. However, the value of capacity retention for bare natural graphite (BNG) is 90.7 % in the same conditions. The electrochemical impedance spectroscopy (EIS) results indicate that the existence of TiO2 nanoparticles in NG−T10 improves the resistance of solid electrolyte interface (SEI) film and charge‐transfer resistance. The NG−T10 also enhances the pouch cell capacity at various current densities up to 4 C.
Carbon Quantum Dot Modified Reduced Graphene Oxide Framework for Improved Alkali Metal Ion Storage Performance
Authors: Jin Shikai , Allam Omar , Lee Kyungbin , Lim Jeonghoon , Lee Michael J. , Loh Sze Hou , Jang Seung Soon , Lee Seung Woo
Published: August 2022

Organic materials with redox‐active oxygen functional groups are of great interest as electrode materials for alkali‐ion storage due to their earth‐abundant constituents, structural tunability, and enhanced energy storage properties. Herein, a hybrid carbon framework consisting of reduced graphene oxide and oxygen functionalized carbon quantum dots (CQDs) is developed via the one‐pot solvothermal reduction method, and a systematic study is undertaken to investigate its redox mechanism and electrochemical properties with Li‐, Na‐, and K‐ions. Due to the incorporation of CQDs, the hybrid cathode delivers consistent improvements in charge storage performance for the alkali‐ions and impressive reversible capacity (257 mAh g−1 at 50 mA g−1), rate capability (111 mAh g−1 at 1 A g−1), and cycling stability (79% retention after 10 000 cycles) with Li‐ion. Furthermore, density functional theory calculations uncover the CQD structure‐electrochemical reactivity trends for different alkali‐ion. The results provide important insights into adopting CQD species for optimal alkali‐ion storage.
A welcome return for the BVA Welsh dinner
Authors: Cotton Helena
Published: August 2022

After a three‐year Covid hiatus we were delighted to once again connect with friends and colleagues at the BVA Welsh dinner, held at Cardiff City Hall on 5 July. Helena Cotton, BVA public affairs manager, reflects on our return to Wales.
Wind turbine nacelle cooling systems: A review
Authors: Fuskele Veeresh , Baredar Prashant , Sarviya Rishindra Mohan , Lal Shiv , Awasthi Shubham
Published: August 2022

The thermal load in the wind turbine nacelle is increasing due to the higher dissipation of heat from the various components in the high unit capacity wind mill. With the motive to develop a sustainable and efficient windmill, research on low cost highly efficient wind turbine nacelle cooling systems has become particularly important. In this review, the prominent waste heat producing sources and the extensively used cooling systems are described. A detailed analysis of the advantages and limitations of each system and the use of various cooling fluids as cooling medium in wind turbine nacelle cooling systems is also discussed. Use of nanofluids as cooling medium in liquid cooling system is also highlighted as it produces a higher thermal performance enhancement. Hence, it is identified as a promising option for a cooling medium and future research.

This article is categorized under:

Wind Power > Systems and Infrastructure

Wind Power > Science and Materials

Energy Infrastructure > Systems and Infrastructure
New advances in pharmaceutical strategies for sensitizing anti‐PD‐1 immunotherapy and clinical research
Authors: Jiang Mengshi , Qin Bing , Li Xiang , Liu Yu , Guan Guannan , You Jian
Published: August 2022

Attempts have been made continuously to use nano‐drug delivery system (NDDS) to improve the effect of antitumor therapy. In recent years, especially in the application of immunotherapy represented by antiprogrammed death receptor 1 (anti‐PD‐1), it has been vigorously developed. Nanodelivery systems are significantly superior in a number of aspects including increasing the solubility of insoluble drugs, enhancing their targeting ability, prolonging their half‐life, and reducing side effects. It can not only directly improve the efficacy of anti‐PD‐1 immunotherapy, but also indirectly enhance the antineoplastic efficacy of immunotherapy by boosting the effectiveness of therapeutic modalities such as chemotherapy, radiotherapy, photothermal, and photodynamic therapy (PTT/PDT). Here, we summarize the studies published in recent years on the use of nanotechnology in pharmaceutics to improve the efficacy of anti‐PD‐1 antibodies, analyze their characteristics and shortcomings, and combine with the current clinical research on anti‐PD‐1 antibodies to provide a reference for the design of future nanocarriers, so as to further expand the clinical application prospects of NDDSs.

This article is categorized under:

Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
[NEt3Me][O3], Synthesis, Crystal Growth and Crystal Structure Analysis
Authors: Schmid Jonas R. , Voßnacker Patrick , Jansen Martin , Riedel Sebastian
Published: August 2022

[NEt3Me][O3] was obtained for the first time by an ion exchange reaction in liquid ammonia. It was thoroughly characterized by X‐Ray diffraction [P21; a=598.51(4) pm, b=1032.03(7) pm, c=723.83(6) pm, β=92.677(3)°, R=0.0384, 15070 reflections] applying non‐spherical and spherical atomic form factors for the refinements. In contrast to previous reported ozonides, [NEt3Me][O3] is the first to adopt the tungsten carbide (WC) motif of cation/ anion arragemnent and shows an untypical hydrogen bond between the central oxygen atom of the ozonide and the cation. Additionally, IR spectroscopy as well as quantum‐chemical calculations were applied to further characterize the compound. The obtained ozonide showed high solubility in ammonia as well as acetonitrile and good properties as a synthon in ozonide chemistry.
On Partee’s “Noun Phrase Interpretation and Type-Shifting Principles”
Authors: Winter Yoad
Published: August 2022

Montague’s classic article “The Proper Treatment of Quantification in Ordinary English” (PTQ, 1973) treated all NP occurrences as quantificational. Partee’s article “Noun Phrase Interpretation and Type-Shifting Principles” (1987) reconciles PTQ’s uniform quantificational strategy with the older distinction between three NP types: entities, predicates and quantifiers. On top of this distinction, Partee introduces operators that allow shifting the denotation of an NP to a different type than the one it is initially assigned. Using these type-shifters, one and the same NP may receive each of the three interpretations. In addition to this synthesis of previous approaches, Partee’s article contains a rather elaborate analysis of predicative NPs, as well as insightful hints about the treatment of definite NPs, nominalization phenomena, plural, mass and generic NPs, and the mathematical principles underlying type-shifting. At a more global level, Partee’s article marks a methodological transition in formal semantics, highlighting general principles that are relevant to different languages and to different linguistic frameworks, rather than technicalities of artificial language fragments. This general account and the new ways it opened for semantic theory, together with the paper’s lucid and friendly style, have made “Noun Phrase Interpretation and Type-Shifting Principles” one of the modern classics in formal semantics. After some necessary background on NPs in PTQ, this review covers the main innovations in Partee’s article, and comments on the work and its influence.
Specification-Guided Learning of Nash Equilibria with High Social Welfare
Authors: Jothimurugan Kishor , Bansal Suguman , Bastani Osbert , Alur Rajeev
Published: August 2022

Reinforcement learning has been shown to be an effective strategy for automatically training policies for challenging control problems. Focusing on non-cooperative multi-agent systems, we propose a novel reinforcement learning framework for training joint policies that form a Nash equilibrium. In our approach, rather than providing low-level reward functions, the user provides high-level specifications that encode the objective of each agent. Then, guided by the structure of the specifications, our algorithm searches over policies to identify one that provably forms an$$\epsilon $$ϵ-Nash equilibrium (with high probability). Importantly, it prioritizes policies in a way that maximizes social welfare across all agents. Our empirical evaluation demonstrates that our algorithm computes equilibrium policies with high social welfare, whereas state-of-the-art baselines either fail to compute Nash equilibria or compute ones with comparatively lower social welfare.
Sampling-Based Verification of CTMCs with Uncertain Rates
Authors: Badings Thom S. , Jansen Nils , Junges Sebastian , Stoelinga Marielle , Volk Matthias
Published: August 2022

We employ uncertain parametric CTMCs with parametric transition rates and a prior on the parameter values. The prior encodes uncertainty about the actual transition rates, while the parameters allow dependencies between transition rates. Sampling the parameter values from the prior distribution then yields a standard CTMC, for which we may compute relevant reachability probabilities. We provide a principled solution, based on a technique called scenario-optimization, to the following problem: From a finite set of parameter samples and a user-specified confidence level, compute prediction regions on the reachability probabilities. The prediction regions should (with high probability) contain the reachability probabilities of a CTMC induced by any additional sample. To boost the scalability of the approach, we employ standard abstraction techniques and adapt our methodology to support approximate reachability probabilities. Experiments with various well-known benchmarks show the applicability of the approach.
Synthesis and Analysis of Petri Nets from Causal Specifications
Authors: de Oliveira Oliveira Mateus
Published: August 2022

Petri nets are one of the most prominent system-level formalisms for the specification of causality in concurrent, distributed, or multi-agent systems. This formalism is abstract enough to be analyzed using theoretical tools, and at the same time, concrete enough to eliminate ambiguities that would arise at implementation level. One interesting feature of Petri nets is that they can be studied from the point of view of true concurrency, where causal scenarios are specified using partial orders, instead of approaches based on interleaving.

On the other hand, message sequence chart (MSC) languages, are a standard formalism for the specification of causality from a purely behavioral perspective. In other words, this formalism specifies a set of causal scenarios between actions of a system, without providing any implementation-level details about the system.

In this work, we establish several new connections between MSC languages and Petri nets, and show that several computational problems involving these formalisms are decidable. Our results fill some gaps in the literature that had been open for several years. To obtain our results we develop new techniques in the realm of slice automata theory, a framework introduced one decade ago in the study of the partial order behavior of bounded Petri nets. These techniques can also be applied to establish connections between Petri nets and other well studied behavioral formalisms, such as the notion of Mazurkiewicz trace languages.
Information Flow Guided Synthesis
Authors: Finkbeiner Bernd , Metzger Niklas , Moses Yoram
Published: August 2022

Compositional synthesis relies on the discovery of assumptions, i.e., restrictions on the behavior of the remainder of the system that allow a component to realize its specification. In order to avoid losing valid solutions, these assumptions should benecessaryconditions for realizability. However, because there are typically many different behaviors that realize the same specification, necessary behavioral restrictions often do not exist. In this paper, we introduce a new class of assumptions for compositional synthesis, which we callinformation flow assumptions. Such assumptions capture an essential aspect of distributed computing, because components often need to act upon information that is available only in other components. The presence of a certain flow of information is therefore often a necessary requirement, while the actual behavior that establishes the information flow is unconstrained. In contrast to behavioral assumptions, which are properties of individual computation traces, information flow assumptions arehyperproperties, i.e., properties of sets of traces. We present a method for the automatic derivation of information-flow assumptions from a temporal logic specification of the system. We then provide a technique for the automatic synthesis of component implementations based on information flow assumptions. This provides a new compositional approach to the synthesis of distributed systems. We report on encouraging first experiments with the approach, carried out with theBoSyHypersynthesis tool.