bluuebunny/crossref_metadata_2025 huggingface dataset:
Hamiltonian Monte Carlo for Simultaneous Interface and Spatial Field Detection (HMCSISFD) and its application to a piping zone interface detection problem
Authors: Koch Michael Conrad , Osugi Misato , Fujisawa Kazunori , Murakami Akira
Published: September 2021

In practice, inverse problems related to explicit interface detection rely on scarcely available information of the background continuous spatial fields. To accurately carry on inversion in such cases, a method called Hamiltonian Monte Carlo for Simultaneous Interface and Spatial Field Detection (HMCSISFD) is developed. Update of the interface parameters is done in a reversible mesh moving framework leading to a change in domain geometry which forces a recomputation of the spatial field covariance function as it is domain dependent. The eigenvalue problem and its derivatives w.r.t. the parameters are solved again on the updated domain to enable dimensionality reduction of the spatial field parameters through the use of the truncated Karhunen‐Loève expansion. This simultaneous parameter update procedure is applied to the detection of the interface and spatial field properties of a piping zone. Inversion is done considering hydraulic head and discharge rate data, with a priori known observation noise, from a carefully designed laboratory seepage flow experiment in a domain consisting a predefined piping zone. The static pipe in the experiment is representative of a pipe in equilibrium beneath an embankment/levee where the current hydraulic gradient isn't sufficient to cause further pipe progression. Markov chains obtained from the HMCSISFD method show convergence and the true interface and spatial field parameters are found to lie well within the 95% high probability density regions and the 0.05 and 0.95 quantiles, respectively, provided a proper choice for the observation noise is made.
Long‐term lower urinary tract sequelae following AUS cuff erosion
Authors: Chertack Nathan A. , Caldwell Kelly M. , Joice Gregory A. , Kavoussi Mehraban , Dropkin Benjamin M. , Ortiz Nicolas M. , Baumgarten Adam S. , Shakir Nabeel A. , Sanders Sarah C. , Hudak Steven J. , Morey Allen F.
Published: September 2021

Aims

To examine the rate of lower urinary tract complications (LUTC) and urinary diversion (UD) after artificial urinary sphincter (AUS) explantation with the acute reconstruction of AUS cuff erosion defects.

Methods

We performed a retrospective study of patients who underwent in‐situ urethroplasty (ISU) for AUS cuff erosion from June 2007 to December 2020. Outcomes included LUTC (urethral stricture, diverticulum, fistula), AUS reimplantation, and UD. Defect size was prospectively estimated acutely and a subanalysis was performed to determine the impact of erosion severity (small erosions [<33% circumferential defect] and large erosions [≥33%]) on these outcomes. Kaplan–Meier curves were created to compare survival between the two groups.

Results

A total of 40 patients underwent ISU for urethral cuff erosion. The median patient age was 76 years old with a median erosion circumference of 46%. The overall LUTC rate was 30% (12/40) with 35% (14/40) of patients requiring permanent UD. Secondary AUS placement occurred in 24/40 (60%) patients with 11/24 (46%) leading to repeat erosion. On subanalysis, small erosion was associated with improved LUTC‐free and UD‐free survival but not associated with AUS reimplantation.

Conclusions

Lower urinary tract complications are common after AUS cuff erosion and can lead to the need for permanent UD. Patients with larger erosions are more likely to undergo UD and reach this end‐stage condition earlier compared to patients with small erosions.
Communication‐based predictive energy management strategy for a hybrid powertrain
Authors: Deng Junpeng , Adelberger Daniel , del Re Luigi
Published: September 2021

Predictive information can significantly improve energy efficiency in a hybrid powertrain, especially for a long drive. Ideally the prediction of a sufficiently long horizon can bring the maximum benefit, however during this horizon the traffic can change, making it impossible to continue the chosen optimal strategy. Due to the limited vision of vehicles' sensors, it is difficult to acquire information far away. Against this background, this article proposes a predictive optimal control strategy in the connected environment. It combines real‐world vehicle‐to‐everything (V2X) information and cloud communication to allow for swift reaction and loss mitigation. More specifically, V2X information is used to detect impending changes on the route and the cloud is used to map these changes onto new constraints on the operation of the HEV. Instead of using “static” V2X information directly, a more realistic prediction method considering the dynamic of traffic is developed. Besides, an update strategy is adopted to timely cope with uncertainties. The performance of the approach is shown by a case study based on real driving cycles in Austria. The results show that the proposed structure is able to improve the performance (mainly fuel efficiency) up to .
Molecular genetic evidence supporting diverse histogenic origins of germ cell tumors
Authors: Jung Seung‐Hyun , Park Hyeon‐Chun , Choi Youn Jin , Song Sang Yong , Chung Yeun‐Jun , Lee Sug Hyung
Published: September 2021

Germ cell tumors (GCTs) originate during the histogenesis of primordial germ cells to mature gametes. Previous studies identified five histogenic mechanisms in ovarian mature teratomas (type I: failure of meiosis I; type II: failure of meiosis II; type III: duplication of the genome of a mature gamete; type IV: no meiosis; and type V: fusion of two different ova), but those of other GCTs remain elusive. In this study, we analyzed 84 GCTs of various pathologic types to identify the histogenesis using single‐nucleotide polymorphism array by analyzing copy‐neutral loss of heterozygosity (CN‐LOH) and copy number alterations (CNAs). We detected types I and II in ovarian teratomas, type III in ovarian teratomas and yolk sac tumors (YSTs), and type IV in all GCT types. The GCTs with multiple‐type histogenesis (I–IV) (ovarian mature/immature teratomas and YST) show meiotic CN‐LOH with scant CNAs. Type IV‐only GCTs are either with mitotic CN‐LOH and abundant CNAs (seminoma, dysgerminoma, testicular mixed GCTs) or with scant CNAs and no CN‐LOH (pediatric testicular and mediastinal teratomas). The development sequences of CN‐LOH and CNA are different between the multiple type (I–IV) GCTs and type IV‐only GCTs. We analyzed two different histologic areas in eight GCTs (one mature teratoma with a mucin‐secreting adenoma, two immature teratomas, and five mixed GCTs). We found that GCTs (mature teratoma, immature teratoma, and mixed GCT) showed different genomic alterations between histologic areas, suggesting that genomic differences within a GCT could accompany histologic differentiation. Of note, we found evidence for collision tumors in a mixed GCT. Our data indicate that GCTs may have various histogenesis and intratumoral genomic differences, which might provide important information for the identification of GCTs, especially for those with different histologic areas. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Weakly supervised annotation‐free cancer detection and prediction of genotype in routine histopathology
Authors: Schrammen Peter Leonard , Ghaffari Laleh Narmin , Echle Amelie , Truhn Daniel , Schulz Volkmar , Brinker Titus J , Brenner Hermann , Chang‐Claude Jenny , Alwers Elizabeth , Brobeil Alexander , Kloor Matthias , Heij Lara R , Jäger Dirk , Trautwein Christian , Grabsch Heike I , Quirke Philip , West Nicholas P , Hoffmeister Michael , Kather Jakob Nikolas
Published: September 2021

Deep learning is a powerful tool in computational pathology: it can be used for tumor detection and for predicting genetic alterations based on histopathology images alone. Conventionally, tumor detection and prediction of genetic alterations are two separate workflows. Newer methods have combined them, but require complex, manually engineered computational pipelines, restricting reproducibility and robustness. To address these issues, we present a new method for simultaneous tumor detection and prediction of genetic alterations: The Slide‐Level Assessment Model (SLAM) uses a single off‐the‐shelf neural network to predict molecular alterations directly from routine pathology slides without any manual annotations, improving upon previous methods by automatically excluding normal and non‐informative tissue regions. SLAM requires only standard programming libraries and is conceptually simpler than previous approaches. We have extensively validated SLAM for clinically relevant tasks using two large multicentric cohorts of colorectal cancer patients, Darmkrebs: Chancen der Verhütung durch Screening (DACHS) from Germany and Yorkshire Cancer Research Bowel Cancer Improvement Programme (YCR‐BCIP) from the UK. We show that SLAM yields reliable slide‐level classification of tumor presence with an area under the receiver operating curve (AUROC) of 0.980 (confidence interval 0.975, 0.984; n = 2,297 tumor and n = 1,281 normal slides). In addition, SLAM can detect microsatellite instability (MSI)/mismatch repair deficiency (dMMR) or microsatellite stability/mismatch repair proficiency with an AUROC of 0.909 (0.888, 0.929; n = 2,039 patients) and BRAF mutational status with an AUROC of 0.821 (0.786, 0.852; n = 2,075 patients). The improvement with respect to previous methods was validated in a large external testing cohort in which MSI/dMMR status was detected with an AUROC of 0.900 (0.864, 0.931; n = 805 patients). In addition, SLAM provides human‐interpretable visualization maps, enabling the analysis of multiplexed network predictions by human experts. In summary, SLAM is a new simple and powerful method for computational pathology that could be applied to multiple disease contexts. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
A review on extraction, chemical treatment, characterization of natural fibers and its composites for potential applications
Authors: Jagadeesh Praveenkumara , Puttegowda Madhu , Mavinkere Rangappa Sanjay , Siengchin Suchart
Published: September 2021

In recent days, natural fiber reinforced polymer composite is more popular due to its extensive properties suitable for various potential applications. The attention towards natural fibers is because of low cost, biodegradable, recyclability, nonabrasive, combustible, lightweight, and nontoxic properties. However, there is a need for furthermore fundamental knowledge for the raw materials processing and fabrication of composite structures, which is still challenging in current days. Natural fiber sources exist all over the world, which is obtained from animals, plants and minerals. The quality of the natural fibers depends on the extraction methods and different processing techniques. These natural fibers surface characteristics could be enhanced by selecting suitable surface treatment and chemical treatment. These fiber treatments reduce the water intake percentage, improve the adhesive nature, and enhance the overall performance of resulting polymer composites. Among all the chemical treatments, alkaline treatment (NaOH) is the most preferred chemical treatment because of its effectiveness and its low cost. This review article proposes the natural fibers detailed classification, composition, structure, properties, and extraction methods, chemical and surface treatments. We also summarize the previous research work findings on the fibers treatment, properties of natural/natural hybrid polymer composites and natural/synthetic hybrid polymer composites with applications.
Grafting of poly(ε‐caprolactone) from Abaca cellulose fibers via ring‐opening polymerization resulting in facile one‐pot biocomposites
Authors: Roy Bernice Lorraine F. , Heinrich Lydia A. , Tayo Lemmuel L. , Malmström Eva , Engström Joakim
Published: September 2021

As efforts to replace nonsustainable plastics increase, biocomposites from cellulose fibers and biodegradable polymers like poly(ε‐caprolactone) (PCL) are promising candidates. The necessary adhesion between fibers and matrix can be achieved by grafting polymeric chains onto the fibers. Herein, we report grafting of PCL onto Abaca fibers (AFs), a one‐pot method to obtain a composite containing grafted fiber and free PCL, and the characterization of prepared composite films. Three parameters for pretreatment (disintegration, drying, and solvent exchange) of AF were compared. Short and long PCL chains with molecular weights below and close to the chain entanglement weight of PCL were grafted from AFs. Using benzyl alcohol as an additional initiator, free PCL was simultaneously prepared. The unreacted monomer was removed by precipitation in water, resulting in ready‐made one‐pot composites. The biocomposites containing the free PCL and PCL‐grafted AFs were further processed by a combination of compounding and hot‐pressing. The analyzed mechanical (tensile) and rheological properties show a large dependence on the lengths of the PCL grafts. The herein‐reported composites pave the way for interesting bio‐based alternatives to plastic, especially looking at the tailoring of material properties.
Characterization of HLA‐A*33:03 epitopes via immunoprecipitation and LC‐MS/MS
Authors: Khan Amir , Shin Ji‐Yon , So Min Kyung , Na Jung‐Hyun , Justesen Sune , Ansari Adnan Ahmad , Ko Byoung Joon , Ahn Sung‐Min
Published: September 2021

Human leukocyte antigen (HLA) class I has more than 18,000 alleles, each of which binds to a set of unique peptides from the cellular degradome. Deciphering the interaction between antigenic peptides and HLA proteins is crucial for understanding immune responses in autoimmune diseases and cancer. In this study, we aimed to characterize the peptidome that binds to HLA‐A*33:03, which is one of the most prevalent HLA‐A alleles in the Northeast Asian population, but poorly studied. For this purpose, we analyzed the HLA‐A*33:03 monoallelic B cell line using immunoprecipitation of HLA‐A and peptide complexes, followed by liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). In this study, we identified 5731 unique peptides that were associated with HLA A*33:03, and experimentally validated the affinity of 40 peptides for HLA‐A*33:03 and their stability in HLA A*33:03‐peptides complexes. To our knowledge, this study represents the largest dataset of peptides associated with HLA‐A*33:03. Also, this is the first study in which HLA A*33:03‐associated peptides were experimentally validated.
Prevalence of collusion in cancer communications: A meta‐analysis
Authors: Sutar Roshan , Chaudhary Pooja , Yadav Vikas
Published: September 2021

Introduction

Collusion is the non‐disclosure of information about diagnosis or prognosis, frequently encountered in cancer care and palliative services. Unraveling collusion is a skill and differences among communication techniques by Health Care Workers have maintained the process of non‐disclosure to patients and caregivers. Identifying the prevalence of collusion in cancer care is required to improve the existing strategies across the world.

Methods

A systematic review of the literature from 1991 to 2020 in the English language was conducted with the protocol registration on PROSPERO ID (CRD 42021249216.) to identify the pooled prevalence of collusion.

Results

By using random effect model, the pooled prevalence estimate among patients for the diagnostic and prognostic collusion was 24.15, (95% CI [17.09; 32.96], Tou2 = 1.0801, I2 = 97.9%, Cochran's Q = 1058.22, df = 21, p‐value < 0.001) and 37.92, (95% CI [22.46; 56.30], Tou2 = 1.9641, I2 = 98.6%, Cochran's Q = 944.26, df = 13, p‐value < 0.001) respectively. There was no difference across subgroups with different types of setting for the interview, WHO regions and trend over the years.

Conclusions

Substantial prevalence of collusion goes unnoticed in cancer care. A meaningful understanding of such a large prevalence requires inquiry into the existing communication paradigm in cancer care across the world. The findings also question the need of formulating uniform interview techniques and structured assessment tools or questionnaires in cancer care to improve the disclosure rates.
Holocene ice wedges of the Kolyma Lowland and January paleotemperature reconstructions based on oxygen isotope records
Authors: Vasil'chuk Yurij K. , Budantseva Nadine A.
Published: September 2021

Ice wedges in the Holocene deposits of alases and floodplains have been studied in the Kolyma Lowland region. Most ice wedges have been found within alases dated to between 11 and 4.2 cal kyr BP, corresponding to the Greenlandian and Northgrippian stages of the Holocene. This study confirms that the greatest intensity of ice wedge growth occurred during ~10.5–6 cal kyr BP. A decrease in their growth was mainly caused by alas draining and reduced sedimentation. In the last 4–4.5 cal kyr BP (defined as the Meghalayan stage of the Holocene), ice wedges continued to grow in old alases, sometimes as a younger generation, as well as within young alases and floodplains of the Kolyma River and its tributaries. Mean January air temperatures were quite stable during the Holocene and varied usually approximately between −33 and −41°C, with a slight cooling during the Meghalayan stage. Minor variations in mean January air temperature may indicate a stability of winter climate of northern Yakutia, probably as a result of the stable influence of the Siberian anticyclone.
Structural insights into the binding of nanobodies LaM2 and LaM4 to the red fluorescent protein mCherry
Authors: Wang Ziying , Li Long , Hu Rongting , Zhong Peiyu , Zhang Yiran , Cheng Shihao , Jiang He , Liu Rui , Ding Yu
Published: September 2021

Red fluorescent proteins (RFPs) are powerful tools used in molecular biology research. Although RFP can be easily monitored in vivo, manipulation of RFP by suitable nanobodies binding to different epitopes of RFP is still desired. Thus, it is crucial to obtain structural information on how the different nanobodies interact with RFP. Here, we determined the crystal structures of the LaM2‐mCherry and LaM4‐mCherry complexes at 1.4 and 1.9 Å resolution. Our results showed that LaM2 binds to the side of the mCherry β‐barrel, while LaM4 binds to the bottom of the β‐barrel. The distinct binding sites of LaM2 and LaM4 were further verified by isothermal titration calorimetry, fluorescence‐based size exclusion chromatography, and dynamic light scattering assays. Mutation of the residues at the LaM2 or LaM4 binding interface to mCherry significantly decreased the binding affinity of the nanobody to mCherry. Our results also showed that LaM2 and LaM4 can bind to mCherry simultaneously, which is crucial for recruiting multiple operation elements to the RFP. The binding of LaM2 or LaM4 did not significantly change the chromophore environment of mCherry, which is important for fluorescence quantification assays, while several GFP nanobodies significantly altered the fluorescence. Our results provide atomic resolution interaction information on the binding of nanobodies LaM2 and LaM4 with mCherry, which is important for developing detection and manipulation methods for RFP‐based biotechnology.
Copper nitrite reductase from Sinorhizobium meliloti 2011: Crystal structure and interaction with the physiological versus a nonmetabolically related cupredoxin‐like mediator
Authors: Ramírez Cintia Soledad , Tolmie Carmien , Opperman Diederik Johannes , González Pablo Javier , Rivas María Gabriela , Brondino Carlos Dante , Ferroni Felix Martín
Published: September 2021

We report the crystal structure of the copper‐containing nitrite reductase (NirK) from the Gram‐negative bacterium Sinorhizobium meliloti 2011 (Sm), together with complex structural alignment and docking studies with both non‐cognate and the physiologically related pseudoazurins, SmPaz1 and SmPaz2, respectively. S. meliloti is a rhizobacterium used for the formulation of Medicago sativa bionoculants, and SmNirK plays a key role in this symbiosis through the denitrification pathway. The structure of SmNirK, solved at a resolution of 2.5 Å, showed a striking resemblance with the overall structure of the well‐known Class I NirKs composed of two Greek key β‐barrel domains. The activity of SmNirK is ~12% of the activity reported for classical NirKs, which could be attributed to several factors such as subtle structural differences in the secondary proton channel, solvent accessibility of the substrate channel, and that the denitrifying activity has to be finely regulated within the endosymbiont. In vitro kinetics performed in homogenous and heterogeneous media showed that both SmPaz1 and SmPaz2, which are coded in different regions of the genome, donate electrons to SmNirK with similar performance. Even though the energetics of the interprotein electron transfer (ET) process is not favorable with either electron donors, adduct formation mediated by conserved residues allows minimizing the distance between the copper centers involved in the interprotein ET process.
Target highlights in CASP14: Analysis of models by structure providers
Authors: Alexander Leila T. , Lepore Rosalba , Kryshtafovych Andriy , Adamopoulos Athanassios , Alahuhta Markus , Arvin Ann M. , Bomble Yannick J. , Böttcher Bettina , Breyton Cécile , Chiarini Valerio , Chinnam Naga babu , Chiu Wah , Fidelis Krzysztof , Grinter Rhys , Gupta Gagan D. , Hartmann Marcus D. , Hayes Christopher S. , Heidebrecht Tatjana , Ilari Andrea , Joachimiak Andrzej , Kim Youngchang , Linares Romain , Lovering Andrew L. , Lunin Vladimir V. , Lupas Andrei N. , Makbul Cihan , Michalska Karolina , Moult John , Mukherjee Prasun K. , Nutt William (Sam) , Oliver Stefan L. , Perrakis Anastassis , Stols Lucy , Tainer John A. , Topf Maya , Tsutakawa Susan E. , Valdivia‐Delgado Mauricio , Schwede Torsten
Published: September 2021

The biological and functional significance of selected Critical Assessment of Techniques for Protein Structure Prediction 14 (CASP14) targets are described by the authors of the structures. The authors highlight the most relevant features of the target proteins and discuss how well these features were reproduced in the respective submitted predictions. The overall ability to predict three‐dimensional structures of proteins has improved remarkably in CASP14, and many difficult targets were modeled with impressive accuracy. For the first time in the history of CASP, the experimentalists not only highlighted that computational models can accurately reproduce the most critical structural features observed in their targets, but also envisaged that models could serve as a guidance for further studies of biologically‐relevant properties of proteins.
Genome‐wide transcriptional response of the causal soybean sudden death syndrome pathogen Fusarium virguliforme to a succinate dehydrogenase inhibitor fluopyram
Authors: Sang Hyunkyu , Chang Hao‐Xun , Choi Sungyu , Son Doeun , Lee Gahee , Chilvers Martin I
Published: September 2021

BACKGROUND

Succinate dehydrogenase inhibitors (SDHIs) have been widely used to manage plant diseases caused by phytopathogenic fungi. Although attention to and use of SDHI fungicides has recently increased, molecular responses of fungal pathogens to SDHIs have often not been investigated. A SDHI fungicide, fluopyram, has been used as a soybean seed treatment and has displayed effective control of Fusarium virguliforme, one of the causal agents of soybean sudden death syndrome. To examine genome‐wide gene expression of F. virguliforme to fluopyram, RNA‐seq analysis was conducted on two field strains of F. virguliforme with differing SDHI fungicide sensitivity in the absence and presence of fluopyram.

RESULTS

The analysis indicated that several xenobiotic detoxification‐related genes, such as those of deoxygenase, transferases and transporters, were highly induced by fluopyram. Among the genes, four ATP‐binding cassette (ABC) transporters were characterized by the yeast expression system. The results revealed that expression of three ABCG transporters was associated with reduced sensitivity to multiple fungicides including fluopyram. In addition, heterologous expression of a major facilitator superfamily (MFS) transporter that was highly expressed in the fluopyram‐insensitive F. virguliforme strain in the yeast system conferred decreased sensitivity to fluopyram.

CONCLUSION

This study demonstrated that xenobiotic detoxification‐related genes were highly upregulated in response to fluopyram, and expression of ABC or MFS transporter genes was associated with reduced sensitivity to the SDHI fungicide. This is the first transcriptomic analysis of the fungal species response to fluopyram and the finding will help elucidate the molecular mechanisms of SDHI resistance. © 2021 Society of Chemical Industry.
A multistate transition model for statin‐induced myopathy and statin discontinuation
Authors: Zhu Yuxi , Chiang Chien‐Wei , Wang Lei , Brock Guy , Milks M. Wesley , Cao Weidan , Zhang Pengyue , Zeng Donglin , Donneyong Macarius , Li Lang
Published: September 2021

The overarching goal of this study was to simultaneously model the dynamic relationships among statin exposure, statin discontinuation, and potentially statin‐related myopathic outcomes. We extracted data from the Indiana Network of Patient Care for 134,815 patients who received statin therapy between January 4, 2004, and December 31, 2008. All individuals began statin treatment, some discontinued statin use, and some experienced myopathy and/or rhabdomyolysis while taking the drug or after discontinuation. We developed a militate model to characterize 12 transition probabilities among six different states defined by use or discontinuation of statin and its associated myopathy or rhabdomyolysis. We found that discontinuation of statin therapy was common and frequently early, with 44.4% of patients discontinuing therapy after 1 month, and discontinuation is a strong indicator for statin‐induced myopathy (risk ratio, 10.8; p < 0.05). Women more likely than men (p < 0.05) and patients aged 65 years and older had a higher risk than those aged younger than 65 years to discontinue statin use or experience myopathy. In conclusion, we introduce an innovative multistate model that allows clear depiction of the relationship between statin discontinuation and statin‐induced myopathy. For the first time, we have successfully demonstrated and quantified the relative risk of myopathy between patients who continued and discontinued statin therapy. Age and sex were two strong risk factors for both statin discontinuation and incident myopathy.
A framework to guide dose & regimen strategy for clinical drug development
Authors: Sander Oliver , Magnusson Baldur , Ludwig Inga , Jullion Astrid , Meille Christophe , Lorand Daniel , Bornkamp Björn , Hinder Markus , Kovacs Steven J. , Looby Michael
Published: September 2021

Optimizing new drug therapies remains a challenge for clinical development, despite the use of ever more sophisticated quantitative methodologies. Although conceptually simple, the idea of finding the right treatment at the right dose for the right patient to ensure an appropriate balance of risks and benefits is challenging and requires a multidisciplinary approach. In this paper, we present a framework developed as a tool for organizing knowledge and facilitating collaboration in development teams.
Metaheuristics for pharmacometrics
Authors: Kim Seongho , Hooker Andrew C. , Shi Yu , Kim Grace Hyun J. , Wong Weng Kee
Published: September 2021

Metaheuristics is a powerful optimization tool that is increasingly used across disciplines to tackle general purpose optimization problems. Nature‐inspired metaheuristic algorithms is a subclass of metaheuristic algorithms and have been shown to be particularly flexible and useful in solving complicated optimization problems in computer science and engineering. A common practice with metaheuristics is to hybridize it with another suitably chosen algorithm for enhanced performance. This paper reviews metaheuristic algorithms and demonstrates some of its utility in tackling pharmacometric problems. Specifically, we provide three applications using one of its most celebrated members, particle swarm optimization (PSO), and show that PSO can effectively estimate parameters in complicated nonlinear mixed‐effects models and to gain insights into statistical identifiability issues in a complex compartment model. In the third application, we demonstrate how to hybridize PSO with sparse grid, which is an often‐used technique to evaluate high dimensional integrals, to search for‐efficient designs for estimating parameters in nonlinear mixed‐effects models with a count outcome. We also show the proposed hybrid algorithm outperforms its competitors when sparse grid is replaced by its competitor, adaptive gaussian quadrature to approximate the integral, or when PSO is replaced by three notable nature‐inspired metaheuristic algorithms.
Electrically Pumped Epitaxially Regrown GaSb‐Based Type‐I Quantum‐Well Surface‐Emitting Lasers with Buried High‐Index‐Contrast Photonic Crystal Layer
Authors: Shterengas Leon , Liu Ruiyan , Kipshidze Gela , Stein Aaron , Lee Won Jae , Hosoda Takashi , Zakharov Dmitri N. , Kisslinger Kim , Belenky Gregory
Published: September 2021

Epitaxially regrown electrically pumped photonic crystal surface‐emitting lasers (PCSELs) emitting near 2 and 2.6 μm are designed, fabricated, and characterized. A high‐index‐contrast photonic crystal layer is incorporated into the GaSb‐based laser heterostructure by air‐hole‐retaining epitaxial regrowth. A square lattice of triangular holes is etched in the top waveguide core layer of the incomplete laser heterostructure. The nanopatterned surface is subsequently cleaned and regrown with AlGaAsSb p‐cladding material. Transmission electron microscopy studies demonstrate uniform regrowth over the nanopatterned GaSb surface. The selected regrowth regimes yield a buried 2D array of elongated air‐holes. The diode PCSELs based on moderately etched nanopatterns demonstrate band‐edge lasing near 2 μm up to room temperatures. The cascade diode PCSELs operate near 2.6 μm with minimum threshold current densities of about 500 A cm−2 achieved at 180 K. The devices generate mW level output in narrow divergence beam emitted from the window in substrate contact. The angle‐resolved electroluminescence measurements reveal a four‐sub‐band band structure with an apparent photonic bandgap corresponding to the buried high‐index‐contrast square photonic crystal layer. The PCSELs made of heterostructures supporting two modes in the vertical direction demonstrate two sets of sub‐bands showing anti‐crossing‐like interaction.
Quercetin inhibiting the PD‐1/PD‐L1 interaction for immune‐enhancing cancer chemopreventive agent
Authors: Jing Lei , Lin Jieru , Yang Yang , Tao Li , Li Yuyin , Liu Zhenxing , Zhao Qing , Diao Aipo
Published: September 2021

Targeting the PD‐1/PD‐L1 immune checkpoints has achieved significant positive results in the treatment of multiple cancers. Quercetin is one of the most abundant dietary flavonoids found in various vegetables and fruits, and has a wide range of biological activities including immunomodulation. Here we report that quercetin dihydrate was screened and shown to inhibit the PD‐1/PD‐L1 interaction. Treatment with quercetin dihydrate promoted the killing activity of T cells on MDA‐MB‐231 and NCI‐H460 cancer cells. Experiments using the xenograft mouse model showed that the growth rate of tumor volumes and masses in the quercetin dihydrate‐treated mice were decreased. Immunohistochemistry of the tumors showed that CD8, GZMB, and IFN‐γ were increased in the quercetin dihydrate‐treated mice. These results suggest that quercetin dihydrate attenuates the inhibitory effect of PD‐L1 on T cells by inhibiting the PD‐1/PD‐L1 interaction, which has an exciting potential to be used as a cancer chemopreventive agent.
Quantum Illumination with Multiple Entangled Photons
Authors: Gallego Torromé Ricardo
Published: September 2021

In this work, a theoretical generalization of Lloyd's quantum illumination model for signal beams described by two entangled photon states is developed. It is shown that the new protocol is more sensitive than Lloyd's model with respect to signal‐to‐noise ratio (SNR) and reduces the required time‐bandwidth product to have the same enhancement in the SNR. The protocol is resilient against noise, potentially resilient against losses, and offers a method to find the range of the target. However, the generation of the required three photon states for the protocol remains a technical problem for its practical implementation.
A novel domain of attraction based synthesis of inverse optimal control
Authors: Prasanna Parvathy , Jacob Jeevamma , Nandakumar Mattida P.
Published: September 2021

This article proposes a novel and systematic methodology for the inverse optimal control (IOC) of a class of input affine nonlinear systems. First, the system is represented in the pseudo‐linear state‐dependent coefficient (SDC) form so as to facilitate the use of matrix algebraic concepts in the design, while preserving the nonlinear system dynamics. Second, the IOC problem which seeks the solution to the Hamilton–Jacobi–Bellman equation is translated to a diagonal stability (D‐stability) problem. Therefore, the general notion of D‐stability, which deals with the characterization of a matrix for the existence of a diagonal matrix such that , is redefined with respect to SDC factored matrices in this work. Consequently, the criteria for the existence (necessary condition) and determination of a diagonal solution (sufficient condition) are formulated in terms of the SDC matrices. It is shown in this work that these criteria can be readily met by the closed‐loop system matrix , for any arbitrary domain in state‐space, by manipulating only the diagonal elements using the diagonal matrix constituted by the IOC feedback. In short, the IOC feedback is designed such that the criteria for D‐stability by the closed‐loop system matrix is fulfilled. Hence this novel design methodology is meaningfully named as “Inverse optimal control via diagonal stabilization” (IOC‐D). The main advantages of IOC‐D include: (i) guaranteed estimate of the domain of attraction (DOA), (ii) Immense flexibility of design, and (iii) guaranteed closed form solution which makes the design procedure analytic and computationally efficient. Numerical simulations validate the theoretical developments and the overall efficiency of the proposed approach.
control of stochastic networked control systems with time‐varying delays: The event‐triggered sampling case
Authors: Zhu Quanxin , Huang Tingwen
Published: September 2021

In this article, we aim to study the robust stabilization problem for a class of stochastic networked control delay systems with time‐varying delays and unknown parameters. By developing an event‐triggered strategy, the robustly exponential stability in mean‐square of the suggested system with an performance is obtained. Furthermore, the robustly exponential stabilization problem in mean‐square is also solved by designing an controller. Compared with many published results in the literature for discrete‐time stochastic systems, our work mainly focuses on the case of continuous‐time stochastic systems. In particular, time‐varying delays and unknown parameters are also considered. Finally, the applications of the theoretical results are illustrated by two numerical examples.
Leveraging real‐world evidence for determining performance goals for medical device studies
Authors: Wang Chenguang , Rosner Gary L. , Bao Tingting , Lu Nelson , Chen Wei‐Chen , Li Heng , Tiwari Ram , Xu Yunling , Yue Lilly Q.
Published: September 2021

Performance goals are numerical target values pertaining to effectiveness or safety endpoints in single‐arm medical device clinical studies. Typically, performance goals are determined at the planning stage of the investigational study under consideration based on summarized outcome information from existing relevant clinical trials. In recent years, there is a growing interest in leveraging real‐world evidence in medical product development. In this article, we introduce a new method for proposing performance goals by leveraging real‐world evidence. The method applies entropy balancing to address possible patient dissimilarities between the study's target patient population and existing real‐world patients, and can take into account operation differences between clinical studies and real‐world clinical practice. An illustrative example is provided to demonstrate how to implement the proposed method for performance goal determination while leveraging real‐world evidence.
Joint modeling of multivariate nonparametric longitudinal data and survival data: A local smoothing approach
Authors: You Lu , Qiu Peihua
Published: September 2021

In many clinical studies, evaluating the association between longitudinal and survival outcomes is of primary concern. For analyzing data from such studies, joint modeling of longitudinal and survival data becomes an appealing approach. In some applications, there are multiple longitudinal outcomes whose longitudinal pattern is difficult to describe by a parametric form. For such applications, existing research on joint modeling is limited. In this article, we develop a novel joint modeling method to fill the gap. In the new method, a local polynomial mixed‐effects model is used for describing the nonparametric longitudinal pattern of the multiple longitudinal outcomes. Two model estimation procedures, that is, the local EM algorithm and the local penalized quasi‐likelihood estimation, are explored. Practical guidelines for choosing tuning parameters and for variable selection are provided. The new method is justified by some theoretical arguments and numerical studies.
Hierarchical 3D Cuprous Sulfide Nanoporous Cluster Arrays Self‐Assembled on Copper Foam as a Binder‐Free Cathode for Hybrid Magnesium‐Based Batteries
Authors: Zhu Guilei , Xia Guanglin , Yu Xuebin
Published: September 2021

On account of easy accessibility, high theoretical volumetric capacity and dendrite‐free magnesium (Mg) anode, Mg battery has a great promise to be next generation rechargeable batteries, yet still remains a challenging task in acquiring fast Mg2+ kinetics and effective cathode materials. Herein, hierarchical 3D cuprous sulfide porous nanosheet decorated nanowire cluster arrays with robust adhesion on copper foam (Cu2S HP/CF), which is employed as a binder‐free conversion cathode material for magnesium/lithium hybrid battery, delivering impressively initial and reversible specific capacity of 383 and 311 mAh g−1 at 100 mA g−1, respectively, which are obviously outperformed corresponding powder cathode in a traditional method by using polymer binder, is reported. Intriguingly, benefiting from the hierarchical nanoporous array architecture and self‐assembly feature, Cu2S HP/CF cathode shows a remarkable cycling stability with a high capacity of 129 mAh g−1 at 300 mA g−1 over 500 cycles. This work not only highlights a guide for designing hierarchical nanoporous materials derived from metal–organic frameworks, but also provides a novel strategy of in situ formation to fabricate binder‐free cathodes.
Phase‐Transfer Exchange Lead Chalcogenide Colloidal Quantum Dots: Ink Preparation, Film Assembly, and Solar Cell Construction
Authors: Yuan Mohan , Wang Xia , Chen Xiao , He Jungang , Li Kanghua , Song Boxiang , Hu Huicheng , Gao Liang , Lan Xinzheng , Chen Chao , Tang Jiang
Published: September 2021

Solution‐processed colloidal quantum dots (CQDs) are promising candidates for the third‐generation photovoltaics due to their low cost and spectral tunability. The development of CQD solar cells mainly relies on high‐quality CQD ink, smooth and dense film, and charge‐extraction‐favored device architectures. In particular, advances in the processing of CQDs are essential for high‐quality QD solids. The phase transfer exchange (PTE), in contrast with traditional solid‐state ligand exchange, has demonstrated to be the most promising approach for high‐quality QD solids in terms of charge transport and defect passivation. As a result, the efficiencies of Pb chalcogenide CQD solar cells have been rapidly improved to 14.0%. In this review, the development of the PTE method is briefly reviewed for lead chalcogenide CQD ink preparation, film assembly, and device construction. Particularly, the key roles of lead halides and additional additives are emphasized for defect passivation and charge transport improvement. In the end, several potential directions for future research are proposed.
Highly Controllable Hierarchically Porous Ag/Ag2S Heterostructure by Cation Exchange for Efficient Hydrogen Evolution
Authors: Xu Huajie , Niu Xiaoxiao , Liu Zhuangzhuang , Sun Mingzi , Liu Zhaodi , Tian Zhimei , Wu Xiaoxia , Huang Bolong , Tang Yu , Yan Chun‐Hua
Published: September 2021

Establishing the hierarchical porous architectures has been considered to be the most efficient approach to realize the efficient mass diffusion and large exposed active sites of designed micro/nanomaterial catalysts for hydrogen evolution reactions (HER). In this work, the nonequivalent cation exchange strategy is developed to fabricate the hierarchically porous Ag/Ag2S heterostructure based on the rapid cation exchange by the metal‐organic framework (MOF)‐derived CoS. The as‐prepared Ag/Ag2S inherits the original 3D hollow morphology of CoS with porous nature, possessing abundant S‐vacancies and lattice strain simultaneously due to the coordination loss and in‐situ epitaxial growth of metallic Ag on the surface. Owing to the optimizations of lattice and electronic structures, the unique hierarchically porous Ag/Ag2S heterostructure exhibits superior catalytic performance than previously reported catalysts derived from MOF. Theoretical calculations have confirmed that the co‐existence of Ag cluster and sulfur vacancies activates the electroactivity of the interfacial defective region to boost the HER process. The binding strength of the proton and energetic trend of HER has been optimized with the formation of Ag/Ag2S heterostructure, which guarantees the efficient generation of H2. This study opens a new strategy for the utilization of the nonequivalent cation exchange strategy to efficiently synthesize advanced electrocatalysts with high performances.
All‐in‐One Nanomedicine: Multifunctional Single‐Component Nanoparticles for Cancer Theranostics
Authors: Cai Yu , Chen Xiaoyi , Si Jingxing , Mou Xiaozhou , Dong Xiaochen
Published: September 2021

The development of cancer diagnostic imaging and treatment is a major concern worldwide. By integrating imaging and therapy into one theranostic nanoplatform for simultaneously detecting tumors, evaluating the targeting ability and timely monitoring therapeutic responses provide more opportunities for precision medicine. Among various theranostic nanosystems, a series of single‐component nanoparticles (NPs) have been developed for “all‐in‐one” theranostics, which presents the unique properties of facile preparation, simple composition, defined structure, high reproducibility, and excellent biocompatibility. Specifically, utilizing single‐component NPs for both diagnostics and therapeutics can reduce the possible numerous untoward side effects and risks to the living body. In this review, the recent progress of multifunctional single‐component NPs in the applications of cancer theranostics is systematically summarized. Notably, the structure design, categories of NPs, targeted strategies, biomedical applications, potential barriers, challenges, and prospects for the future clinical practice of this rapidly growing field are discussed.
A Metallic Ion‐Induced Self‐Assembly Enabling Nanowire‐Based Aerogels
Authors: Shang Qi‐Guo , Wang Kang , Li Lin‐Ge , He Zhen , Jiang Hui‐Jun , Zhu Jian‐Hua , Liu Jian‐Wei
Published: September 2021

The controlled assembly of nanowires is one of the key challenges in the development of a range of functional 3D aerogels with unique physicochemical properties for practical applications. However, the deep understanding of the dynamic assemble process for fabricating nanowire aerogels remains elusive. Herein, a facile strategy is presented for the metallic ion‐induced assembly of nanowires into macroscopic aerogels via a solution‐based process. This method enables the interconnecting between polymer‐decorated nanowires via metallic coordination, resulting in plenty of nanowire bundles with the same orientation. Besides, the coordinated binding strength of nanowires with different metallic ions is also discussed. The assembly mechanism that the metallic ions induced dynamic behavior of nanowires is revealed via molecular dynamics theoretical evaluation. These findings benefit for constructing nanowire‐based aerogels with unique structural features and multi‐function, which pave new opportunities for other material systems.
Optimizing checkpoint‐based fault‐tolerance in distributed stream processing systems: Theory to practice
Authors: Jayasekara Sachini , Karunasekera Shanika , Harwood Aaron
Published: September 2021

Fault‐tolerance is an essential part of a stream processing system that guarantees data analysis could continue even after failures. State‐of‐the‐art distributed stream processing systems use checkpointing to support fault‐tolerance for stateful computations where the state of the computations is periodically persisted. However, the frequency of performing checkpoints impacts the performance (utilization, latency, and throughput) of the system as the checkpointing process consumes resources and time that can be used for actual computations. In practice, systems are often configured to perform checkpoints based on crude values ignoring factors such as checkpoint and restart costs, leading to suboptimal performance. In our previous work, we proposed a theoretical optimal checkpoint interval that maximizes the system utilization for stream processing systems to minimize the impact of checkpointing on system performance. In this article, we investigate the practical benefits of our proposed theoretical optimal by conducting experiments in a real‐world cloud setting using different streaming applications; we use Apache Flink, a well‐known stream processing system for our experiments. The experiment results demonstrate that an optimal interval can achieve better utilization, confirming the practicality of the theoretical model when applied to real‐world applications. We observed utilization improvements from 10% to 200% for a range of failure rates from 0.3 failures per hour to 0.075 failures per minute. Moreover, we explore how performance measures: latency and throughput are affected by the optimal interval. Our observations demonstrate that significant improvements can be achieved using the optimal interval for both latency and throughput.