bluuebunny/crossref_metadata_2025_split huggingface dataset:
Control problems for energy harvester model and interpolation in Hardy space
Authors: Shubov Marianna A. 
Published: January 2020

AbstractThree control problems for the system of two coupled differential equations governing the dynamics of an energy harvesting model are studied. The system consists of the equation of an Euler–Bernoulli beam model and the equation representing the Kirchhoff's electric circuit law. Both equations contain coupling terms representing the inverse and direct piezoelectric effects. The system is reformulated as a single evolution equation in the state space of 3‐component functions. The control is introduced as a separable forcing term on the right‐hand side of the operator equation. The first control problem deals with an explicit construction of that steers an initial state to zero on a time interval [0, T]. The second control problem deals with the construction of such that the voltage output is equal to some given function (with being given as well). The third control problem deals with an explicit construction of both the force profile, , and the control, , which generate the desired voltage output . Interpolation theory in the Hardy space of analytic functions is used in the solution of the second and third problems.
Low‐dose megavoltage cone‐beam computed tomography using a novel multi‐layer imager (MLI)
Authors: Myronakis Marios , Huber Pascal , Lehmann Mathias , Fueglistaller Rony , Jacobson Matthew , Hu Yue‐Houng , Baturin Paul , Wang Adam , Shi Mengying , Harris Thomas , Morf Daniel , Berbeco Ross 
Published: January 2020

PurposeThe feasibility of low‐dose megavoltage cone‐beam acquisition (MVCBCT) using a novel, high detective quantum efficiency (DQE) multi‐layer imager (MLI) was investigated. The aim of this work was to reconstruct MVCBCT images using the MLI at different total dose levels, and assess Hounsfield Unit (HU) accuracy, noise and contrast‐to‐noise ratio (CNR) for low‐dose megavoltage cone‐beam acquisition.MethodsThe MLI has four stacked layers; each layer contains a combination of copper filter/converter, gadolinium oxysulfide (GOS) scintillator and a‐Si detector array. In total, 720 projections of a CATPHAN® phantom were acquired over 360° at 2.5, 6, and 6 MV flattening filter free (FFF) beam energies on a Varian TrueBeam LINAC. The dose per projection was 0.01, 0.0167, and 0.05 MU for 2.5, 6, and 6 MV FFF, respectively. MVCBCT images were reconstructed with varying numbers of projections to provide a range of doses for evaluation. Hounsfield Unit uniformity, accuracy, noise and CNR were estimated. Improvements were quantified relative to the standard AS1200 single‐layer imager.ResultsAverage HU uniformity for the MLI reconstructions was within a range of 95%‐99% for all of the energies studied. Relative electron density estimation from HU values was within 0.4% ± 1.8% from nominal values. The CNR for MVCBCT based on MLI projections was 2–4× greater than from AS1200 projections. The 2.5 MV beam acquisition with the MLI exhibited the lowest noise and the best balance between CNR and dose for low‐dose reconstructions.ConclusionsMegavoltage cone‐beam acquisition imaging with a novel MLI prototype mounted on a clinical linear accelerator demonstrated substantial improvement over the standard AS1200 EPID. Further optimization of MVCBCT reconstruction, particularly for 2.5 MV acquisitions, will improve image metrics. Overall, the MLI improves CNR at substantially lower doses than currently required by conventional detectors. This new high DQE detector could provide high‐quality MVCBCT at clinically acceptable doses.
Correlation of plasma metabolites with glucose and lipid fluxes in human insulin resistance
Authors: Hartstra Annick V. , de Groot Pieter F. , Mendes Bastos Diogo , Levin Evgeni , Serlie Mireille J. , Soeters Maarten R. , Pekmez Ceyda T. , Dragsted Lars O. , Ackermans Mariette T. , Groen Albert K. , Nieuwdorp Max 
Published: January 2020

SummaryObjectiveInsulin resistance develops prior to the onset of overt type 2 diabetes, making its early detection vital. Direct accurate evaluation is currently only possible with complex examinations like the stable isotope‐based hyperinsulinemic euglycemic clamp (HIEC). Metabolomic profiling enables the detection of thousands of plasma metabolites, providing a tool to identify novel biomarkers in human obesity.DesignLiquid chromatography mass spectrometry–based untargeted plasma metabolomics was applied in 60 participants with obesity with a large range of peripheral insulin sensitivity as determined via a two‐step HIEC with stable isotopes [6,6‐2H2]glucose and [1,1,2,3,3‐2H5]glycerol. This additionally enabled measuring insulin‐regulated lipolysis, which combined with metabolomics, to the knowledge of this research group, has not been reported on before.ResultsSeveral plasma metabolites were identified that significantly correlated with glucose and lipid fluxes, led by plasma (gamma‐glutamyl)citrulline, followed by betaine, beta‐cryptoxanthin, fructosyllysine, octanylcarnitine, sphingomyelin (d18:0/18:0, d19:0/17:0) and thyroxine. Subsequent machine learning analysis showed that a panel of these metabolites derived from a number of metabolic pathways may be used to predict insulin resistance, dominated by non‐essential amino acid citrulline and its metabolite gamma‐glutamylcitrulline.ConclusionThis approach revealed a number of plasma metabolites that correlated reasonably well with glycemic and lipolytic flux parameters, measured using gold standard techniques. These metabolites may be used to predict the rate of glucose disposal in humans with obesity to a similar extend as HOMA, thus providing potential novel biomarkers for insulin resistance.
Prekallikrein – an emerging therapeutic target for Klebsiella pneumoniae infection?†
Authors: Lam Zena , Condliffe Alison M 
Published: January 2020

AbstractKlebsiella pneumoniae is a Gram‐negative bacterium that is increasingly difficult to treat due to the emergence of multidrug resistant strains. In a recent article, Ding et al demonstrate that prekallikrein depletion in mice followed by intranasal instillation of K. pneumoniae leads to a reduced bacterial burden and prolonged host survival, together with evidence of reduced distant organ damage. These effects are apparently independent of the role of prekallikrein in the contact system, and are associated with transcriptional changes relevant to innate immunity in the lung, established prior to infection. This study highlights the importance of further investigating the role of prekallikrein and other contact cascade components in host defence to counter K. pneumoniae (and perhaps other pathogens), with an overall aim of identifying potential therapeutic targets relevant to pulmonary infection with such resistant pathogens. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Topical sirolimus for the treatment of cutaneous manifestations of vascular anomalies: A case series
Authors: Badia Priscila , Ricci Kiersten , Gurria Juan P. , Dasgupta Roshni , Patel Manish , Hammill Adrienne 
Published: January 2020

AbstractBackgroundVascular anomalies (VA), characterized by the abnormal development or growth of blood and/or lymphatic vessels, encompasses a spectrum of conditions with a range of symptoms and complications. VA are frequently associated with cutaneous complications that can cause significant morbidity. Systemic sirolimus has previously been shown to be effective in the treatment of complicated VA. There are limited studies to date on the use of topical sirolimus for the treatment of cutaneous manifestations of VA.MethodsRetrospective review of medical records of pediatric patients with VA treated with topical sirolimus at a single quaternary pediatric institution. Response was determined by clinical subjective and objective measures of improvement.ResultsTwenty‐three patients with cutaneous VA manifestations were treated with topical sirolimus. Median age was 14 (range 4‐27 years). The main indication for treatment was complication of lymphatic blebbing (82%, n = 19) including lymphatic fluid leakage, bleeding, pain, pruritus, swelling, or recurrent infection. Treatment course ranged from 109 to 1424 days with median of 622 days. No major side effects were reported. Eighty‐six percent of patients (n = 20) had subjective or objective improvement of cutaneous lesions. Lymphatic blebbing complications improved in 90% (n = 17) of individuals. Eighty‐two percent (n = 14) of patients not receiving concurrent systemic sirolimus demonstrated improvement with topical therapy. One patient electively stopped treatment due to pruritus and burning sensation.ConclusionTopical sirolimus appears to be a beneficial therapy for lymphatic blebbing associated with lymphatic malformations or mixed malformations with a lymphatic component, although benefit in other VA remains unclear. Topical sirolimus was well‐tolerated with minimal side effects.
Single polymer composite sheets from polypropylene nonwoven fabric and films. Influence of processing conditions on final properties
Authors: Vazquez Yamila V. , Castillo Luciana A. , Barbosa Silvia E. 
Published: January 2020

AbstractSingle polypropylene (PP) composites from a film/nonwoven fabric/film was obtained by hot calendering in order to develop recyclable, flexible, and low‐cost sheets. Processing temperature (Tp) influence on morphology and mechanical properties of developed single composites was analyzed. Two different values of roll temperature (140 and 150°C) were studied, keeping constant rotation speed and rolls distance. Results revealed notable differences in materials microstructure induced by a difference of only 10°C in Tp. Sheets obtained at 140°C presented a well‐defined film/nonwoven fabric/film structure, meanwhile the highest Tp led to a greater melting extent of external films which penetrate into the fabric, creating a more compact structure. Moreover, results confirmed that changes in Tp can induce a differential mechanical performance showing higher strength, and ductility in sheets processed at 150°C. Homogeneous sheets with good mechanical behavior, proper nonwoven fabric/films adhesion, and uniform thickness were obtained.
Understanding and monitoring the capacitance‐voltage technique for the characterization of tandem solar cells
Authors: Leon Cyril , Le Gall Sylvain , Gueunier‐Farret Marie‐Estelle , Brézard‐Oudot Aurore , Jaffre Alexandre , Moron Nicolas , Vauche Laura , Medjoubi Karim , Veinberg Vidal Elias , Longeaud Christophe , Kleider Jean‐Paul 
Published: January 2020

AbstractThis paper presents a simple and nondestructive method to determine doping densities and built‐in potential of subcells by adapting the well‐known capacitance‐voltage (C‐V) technique to two‐terminal (2 T) tandem solar cells. Because of the electrical coupling between the two subcells in a monolithic 2 T tandem solar cell, the standard method using a Mott‐Schottky plot (1/C2 vs V) cannot be applied. Using numerical modeling, it is demonstrated that, by under chosen illumination conditions where only one subcell can absorb the light, it is possible to explore the bias dependence of the capacitance and to extract the parameters of the other subcell if the appropriate frequency conditions are present. This method is experimentally applied to an AlGaAs/Si tandem cell, and parameters of both AlGaAs and Si cells are extracted. Finally, the validity of that method is assessed by the very good agreement obtained when comparing the values extracted from our measurements on the tandem cell to those extracted from measurements on isotype cells and to the values targeted during the fabrication process of the AlGaAs/Si tandem solar cell.
Differences in the chitinolytic activity of mammalian chitinases on soluble and insoluble substrates
Authors: Barad Benjamin A. , Liu Lin , Diaz Roberto E. , Basilio Ralp , Van Dyken Steven J. , Locksley Richard M. , Fraser James S. 
Published: January 2020

AbstractChitin is an abundant polysaccharide used by many organisms for structural rigidity and water repulsion. As such, the insoluble crystalline structure of chitin poses significant challenges for enzymatic degradation. Acidic mammalian chitinase, a processive glycosyl hydrolase, is the primary enzyme involved in the degradation of environmental chitin in mammalian lungs. Mutations to acidic mammalian chitinase have been associated with asthma, and genetic deletion in mice increases morbidity and mortality with age. We initially set out to reverse this phenotype by engineering hyperactive acidic mammalian chitinase variants. Using a screening approach with commercial fluorogenic substrates, we identified mutations with consistent increases in activity. To determine whether the activity increases observed were consistent with more biologically relevant chitin substrates, we developed new assays to quantify chitinase activity with insoluble chitin, and identified a one‐pot fluorogenic assay that is sufficiently sensitive to quantify changes to activity due to the addition or removal of a carbohydrate‐binding domain. We show that the activity increases from our directed evolution screen were lost when insoluble substrates were used. In contrast, naturally occurring gain‐of‐function mutations gave similar results with oligomeric and insoluble substrates. We also show that activity differences between acidic mammalian chitinase and chitotriosidase are reduced with insoluble substrate, suggesting that previously reported activity differences with oligomeric substrates may have been driven by differential substrate specificity. These results highlight the need for assays against physiological substrates when engineering metabolic enzymes, and provide a new one‐pot assay that may prove to be broadly applicable to engineering glycosyl hydrolases.
Immunological characterization of HM5023507, an orally active PI3Kδ/γ inhibitor
Authors: Cai Yu , Yu Jun , Ren Ping , He Jianlin , Wu Zhipeng , Xiao Kun , Jia Hong , Wang Jian , Sai Yang , Dai Guangxiu , Li Xiong , Su Weiguo , Ngo Karen , Castro Glenda , Acton Paul D. , Fung‐Leung Wai‐Ping , Edwards James P. , Venable Jennifer , Rao Tadimeti S. 
Published: January 2020

AbstractPhosphoinositide 3‐kinases, delta (PI3Kδ) and gamma (PI3Kγ) are enriched in immune cells and regulate the development and function of innate and adaptive immunity. Dual PI3Kδγ inhibitors are considered high value targets for their potential to treat a variety of immune‐mediated diseases, but their discovery has been challenging. Here we describe the preclinical pharmacology of HM5023507, an orally active dual inhibitor of δγ isoforms in immune signaling. HM5023507 inhibited PI3Kδ and PI3Kγ isoforms with greater than 100‐fold selectivity against PI3Kα and PI3Kβ in recombinant enzymatic assays and in primary human immune cells with an exquisite selectivity against other targets. HM5023507 attenuated the PI3Kδ/γ signaling in human basophils (IC50: 42/340 nmol/L; selectivity ratio ~1:8). HM5023507 attenuated the activation and function of human B and T cells, Th17 differentiation of CD4 T cells in the blood of healthy donors and rheumatoid arthritis patients, and cytokine and IgG production in human T and B cell cocultures, in vitro. Orally dosed HM5023507 attenuated PI3K δ/γ‐mediated immune signaling in the rat in a dose‐related manner. In addition, HM5023507 inhibited semiestablished collagen‐induced arthritic inflammation in the rats (ED50 of 0.25mg/kg, p.o. BID or 0.5 mg/kg, QD, AUC: 1422 ng/mL*h), improved histopathology‐ and micro‐computed tomography (µCT)‐based indices of joint damage, bone destruction, and attenuated the levels of anti‐collagen antibody, with an overall anti‐inflammatory profile matching that of a TNFα neutralizing antibody. The PI3K δγ inhibitory profile of HM5023507 and its selectivity make it a useful tool to further delineate immunobiology of dual PI3K δγ targeting.
A flexible LEO satellite modem with Ka‐band RF frontend for a data relay satellite system
Authors: Katona Zoltán , Gräßlin Michael , Donner Anton , Kranich Norman , Brandt Hartmut , Bischl Hermann , Brück Martin 
Published: January 2020

SummaryFrom a geostationary Earth orbit (GEO) satellite's perspective, a low Earth orbit (LEO) satellite is visible on more than half of its orbit. Albeit the free‐space loss of an inter‐satellite link is much higher than the one of a direct ground link, considerable data rates and download volumes can be achieved. In this paper, we describe the system architecture of an integrated approach for a data relay satellite system and the development of LEO satellite and ground station modems. The approach allows serving several small and inexpensive LEO satellites at the same time both with low rate telemetry/telecommand links and with high rate download of sensor data.
Hydrogels for Medical and Environmental Applications
Authors: Jayakumar Anjali , Jose Vishal K. , Lee Jong‐Min 
Published: January 2020

AbstractHydrogels are heavily‐hydrated 3D microliths having loose, porous structures. Unlike organogels, elastomers, and carbohydrates, hydrogels are structures with water as a continuous phase/solvent. Being water‐based, they provide a lot of scope for facile improvizations in their structure and in introducing chemical functionalities. They can house various functional materials in their highly porous networks, making them potential candidates for diverse applications. Various possibilities in using different starting materials for hydrogels are described herein, and it is shown how choosing and optimizing these components that make up the hydrogel can modify their properties. Studying hydrogels and their formulations will enable the understanding of their multifunctional properties. External stimuli‐responsive and functional systems can be designed out of these microliths to suit a wide range of applications like biosensing, cancer therapy, regenerative medicine, drug delivery, environmental parameter sensing, water desalination, heavy‐metal adsorption, and water treatment. Environmental degradation is occurring at an alarming rate, cascading the adverse effects on the environment but also causing detrimental effects in public health. In this review, multiple perspectives from state‐of‐the‐art literature are brought together to examine hydrogels as very powerful, sustainable, cost‐effective, and simple solutions for the betterment of the environment and subsequently, public health.
DNA-PK: gatekeeper for IKKγ/NEMO nucleocytoplasmic shuttling in genotoxic stress-induced NF-kappaB activation
Authors: Medunjanin Senad , Putzier Maximilian , Nöthen Till , Weinert Sönke , Kähne Thilo , Luani Blerim , Zuschratter Werner , Braun-Dullaeus Ruediger C. 
Published: January 2020

AbstractThe transcription factors of the nuclear factor κB (NF-κB) family play a pivotal role in the cellular response to DNA damage. Genotoxic stress-induced activation of NF-κB differs from the classical canonical pathway by shuttling of the NF-κB Essential Modifier (IKKγ/NEMO) subunit through the nucleus. Here, we show that DNA-dependent protein kinase (DNA-PK), an enzyme involved in DNA double-strand break (DSB) repair, triggers the phosphorylation of NEMO by genotoxic stress, thereby enabling shuttling of NEMO through the nucleus with subsequent NF-κB activation. We identified serine 43 of NEMO as a DNA-PK phosphorylation site and point mutation of this serine to alanine led to a complete block of NF-κB activation by ionizing radiation (IR). Blockade of DNA-PK by a specific shRNA or by DNA-PKcs-deficient cells abrogated NEMO entry into the nucleus, as well. Accordingly, SUMOylation of NEMO, a prerequisite of nuclear NEMO, was abolished. Based on these observations, we propose a model in which NEMO phosphorylation by DNA-PK provides the first step in the nucleocytoplasmic trafficking of NEMO.
Dissipative Solutions and Semiflow Selection for the Complete Euler System
Authors: Breit Dominic , Feireisl Eduard , Hofmanová Martina 
Published: January 2020

AbstractTo circumvent the ill-posedness issues present in various models of continuum fluid mechanics, we present a dynamical systems approach aiming at the selection of physically relevant solutions. Even under the presence of infinitely many solutions to the full Euler system describing the motion of a compressible inviscid fluid, our approach permits to select a system of solutions (one trajectory for every initial condition) satisfying the classical semiflow property. Moreover, the selection respects the well accepted admissibility criteria for physical solutions, namely, maximization of the entropy production rate and the weak–strong uniqueness principle. Consequently, strong solutions are always selected whenever they exist and stationary states are stable and included in the selection as well. To this end, we introduce a notion of dissipative solution, which is given by a triple of density, momentum and total entropy defined as expectations of a suitable measure-valued solution.
Immunhistochemische und molekularpathologische Diagnostik von Lungenkarzinomen
Authors: Wagner Britta Janina , Buettner Reinhard 
Published: January 2020

ZusammenfassungDie Therapie der Lungenkarzinome hat binnen der letzten 15 Jahre einen revolutionären Wandel erfahren. Dank zielgerichteter Therapien, insbesondere Thyrosinkinaseinhibitoren (TKI), konnte die Prognose der Patienten deutlich verbessert werden. Aktuell rekrutierende Studien testen unter anderem neue MET-, KRAS-, ROS1-, RET- und NTRK-Inhibitoren. Erste klinische Daten sind vielversprechend, sodass es auch zukünftig Pathologen und Onkologen vor eine Herausforderung stellt, stets alle Facetten differenzierter Therapieentscheidungen im Blick zu halten. Die präzise Klassifikation von Lungenkarzinomen anhand immunhistochemischer und molekularpathologischer Analysen ist heute für die weitere Therapie und Prognose des Patienten von zentraler Bedeutung. Hinzu kommt, dass neue Technologien der Biopsiegewinnung Minihistologien oder zytologische Proben in höchster diagnostischer Qualität liefern. Aufgrund der Komplexität der notwendigen Diagnostik ist daher ein strategisches Vorgehen erforderlich, um unnötigen Materialverlust zu vermeiden. Ziel dieser Abhandlung ist es, eine aktuelle Übersicht für eine effiziente und zielgerichtete Diagnostik unter Berücksichtigung der aktuellen Studienlage zu erstellen.