bluuebunny/crossref_metadata_2025_split huggingface dataset:
Testing miniaturized extraction chromatography protocols for combined 87Sr/86Sr and δ88/86Sr analyses of pore water by MC‐ICP‐MS
Authors: Argentino Claudio , Lugli Federico , Cipriani Anna , Panieri Giuliana 
Published: May 2021

AbstractWe tested two miniaturized extraction chromatography protocols for strontium isolation based on 300 μL (Protocol 1) and 30 μL (Protocol 2) column volumes of Sr‐Spec resin, for the simultaneous determination of 87Sr/86Sr and δ88/86Sr by MC‐ICP‐MS. The accuracy and precision of the Sr isotope ratios have been evaluated by analyzing JCt‐1 and SRM 1640a reference materials, resulting in a reproducibility of 87Sr/86Sr and δ88/86Sr values of 0.000026 and 0.04‰ (Protocol 1) (2SD, n = 3), and of 0.000074 and 0.13‰ (Protocol 2) (2SD, n = 4), respectively. The Sr isotopic composition of SRM 1640a, presented here for the first time, is 87Sr/86Sr = 0.708790 ± 0.000062 and δ88/86Sr = 0.07 ± 0.10‰ (2SD, n = 6). Protocols 1 and 2 were successfully applied to pore waters extracted from marine sediment cores from the northern Barents Sea. Our results demonstrate that both protocols attain accurate 87Sr/86Sr ratios and allow the detection of natural variations in δ88/86Sr in marine pore waters. Compared to previous Sr/matrix separation methods, Protocol 2 is significantly less costly, making it particularly suitable for large‐scale oceanological and limnological studies.
The Vibrant Interplay of Light and Self‐Reporting Macromolecular Architectures
Authors: Geiselhart Christina M. , Mutlu Hatice 
Published: May 2021

AbstractInspired by nature, notable efforts have been made towards the exploration of self‐reporting polymers within the last decades. Whereas the majority of the previously reported self‐reporting polymers deliberately relies on a diverse set of mechanisms triggered via different stimuli (e.g., mechanical, thermal, pH, solvation, light, and chemical amongst others), light plays a ubiquitous role not only as a remote trigger, but also as non‐destructive readout signal for the practical applications of self‐reporting polymers. Due to the ever‐growing interest within the respective field (e.g., load bearing materials, nanotechnology, biomedicine, or theranostics), herein a synthetic overview is presented with the aim to provide an informative perspective on challenges facing the vibrant interplay of light and self‐reporting macromolecular architectures.
Overcoming challenges of HERG potassium channel liability through rational design: Eag1 inhibitors for cancer treatment
Authors: Toplak Žan , Hendrickx Louise A. , Abdelaziz Reham , Shi Xiaoyi , Peigneur Steve , Tomašič Tihomir , Tytgat Jan , Peterlin‐Mašič Lucija , Pardo Luis A. 
Published: May 2021

AbstractTwo decades of research have proven the relevance of ion channel expression for tumor progression in virtually every indication, and it has become clear that inhibition of specific ion channels will eventually become part of the oncology therapeutic arsenal. However, ion channels play relevant roles in all aspects of physiology, and specificity for the tumor tissue remains a challenge to avoid undesired effects. Eag1 (KV10.1) is a voltage‐gated potassium channel whose expression is very restricted in healthy tissues outside of the brain, while it is overexpressed in 70% of human tumors. Inhibition of Eag1 reduces tumor growth, but the search for potent inhibitors for tumor therapy suffers from the structural similarities with the cardiac HERG channel, a major off‐target. Existing inhibitors show low specificity between the two channels, and screenings for Eag1 binders are prone to enrichment in compounds that also bind HERG. Rational drug design requires knowledge of the structure of the target and the understanding of structure–function relationships. Recent studies have shown subtle structural differences between Eag1 and HERG channels with profound functional impact. Thus, although both targets' structure is likely too similar to identify leads that exclusively bind to one of the channels, the structural information combined with the new knowledge of the functional relevance of particular residues or areas suggests the possibility of selective targeting of Eag1 in cancer therapies. Further development of selective Eag1 inhibitors can lead to first‐in‐class compounds for the treatment of different cancers.
Theory of continuous inverseclass‐Epower amplifier modes andcontinuous‐mode self‐distortion
Authors: de Almeida Jorge Virgilio , Wu Ke 
Published: May 2021

AbstractA closed‐form solution for the continuous inverse class E (class E−1) design space is presented for the first time1. Analogous to the class‐E power amplifier (PA) modes, the zero current and its derivative conditions needed for the class E−1switching action can also be shown to be satisfied with any second harmonic susceptance. The complementary relationship between the continuous PA modes for class E and class E−1are analytically proven. Signal integrity limitations on the continuous class E and class E−1PA modes are demonstrated to exist and to limit the useful range of solutions of the design space.2Consequently, the maximum achievable bandwidth using the continuum of solutions in both class E/E−1is not 2 octaves as previously reported but only 1 octave.
Micro‐electrodes for in situ temperature and bio‐impedance measurement
Authors: Leung Timothy Ka Wai , Ji Xudong , Peng Boyu , Chik Gary Kwok Ki , Dai Derek Shui Hong Siddhartha , Fang Ge , Zhang Tengfei , Cheng Xing , Kwok Ka Wai , Tsang Anderson Chun On , Leung Gilberto Ka Kit , Chan Paddy Kwok Leung 
Published: May 2021

AbstractWith fast recovery time and effective in situ tumor tissue killing ability, thermal ablation has become a popular treatment for tumors compared with chemotherapy and radiation. The thermal dose measurement of current technology is usually accompanied by monitoring a large area impedance across two ablation catheters and the localized impedance measurement is difficult to achieve. In this work, thermal‐resistive sensor and impedance sensor are fabricated on the curved surface of a capillary tube with 1 mm outer diameter. The device is applied for real‐time in situ tissue impedance monitoring during thermal ablation. The calibrated thermal‐resistive sensors have an average temperature coefficient of resistance (TCR) of 0.00161 ± 5.9% °C‐1 with an accuracy of ±0.7 °C. By adding electro‐polymerized PEDOT:PSS (poly(3,4‐ethylenedioxythiophene)‐poly(styrenesulfonate)) on the 300 µm diameter gold electrodes, the interface impedance reduces two orders from 408 to 3.7 kΩ at 100 Hz. The Randles equivalent circuit model fittings show a two‐order improvement in the electrode capacitance from 7.29 to 753 nF. In the ex vivo porcine liver laser ablation test, the temperature of the porcine liver tissue can reach 70°C and the impedance would drop by 50% in less than 5 minutes. The integration of laser ablation fiber with the impedance and temperature sensors can further expand the laser ablation technique to smaller scale and for precise therapeutics.
Dynamically scheduling and maintaining a flexible server
Authors: Huang Jefferson , Down Douglas G. , Lewis Mark E. , Wu Cheng‐Hung 
Published: May 2021

AbstractDeciding how to jointly schedule jobs and perform preventive maintenance is a fundamental problem in flexible manufacturing systems, particularly those arising in semiconductor manufacturing. At the same time, past work in this area shows that, even when there is only one station and one type of job, identifying policies that minimize the amount of work‐in‐process (WIP) is a difficult problem. In this paper, we study a single‐station version of this problem with an arbitrary number of job classes, with the objective of minimizing average maintenance costs plus the weighted average amount of WIP. We identify conditions under which it suffices to schedule jobs according to both a server‐state‐dependent version of the cμ‐rule, and a static cμ‐rule where the average service rates are used. One of these conditions states that the ratio between the service rates should remain constant as the server deteriorates. When this assumption does not hold, scheduling with the cμ‐rule can in fact lead to an unstable system; we illustrate this using a simple example. On the other hand, we also present numerical evidence that cμ‐based scheduling performs well compared to other scheduling rules, and relative to a policy based on solving a Markov decision process.
Phase I Trial of Cemiplimab, Radiotherapy, Cyclophosphamide, and Granulocyte Macrophage Colony-Stimulating Factor in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
Authors: Babiker Hani , Brana Irene , Mahadevan Daruka , Owonikoko Taofeek , Calvo Emiliano , Rischin Danny , Moreno Victor , Papadopoulos Kyriakos P. , Crittenden Marka , Formenti Silvia , Giralt Jordi , Garrido Pilar , Soria Ainara , Hervás-Morón Asunción , Mohan Kosalai Kal , Fury Matthew , Lowy Israel , Mathias Melissa , Feng Minjie , Li Jingjin , Stankevich Elizabeth 
Published: May 2021

Abstract

Lessons Learned

Background
Refractory and metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) generally does not respond to PD-1 inhibitor monotherapy. Cemiplimab is a human anti–PD-1 monoclonal antibody. An expansion cohort enrolled patients with R/M HNSCC in a phase I study combining cemiplimab plus radiation therapy (RT), cyclophosphamide, and granulocyte macrophage colony-stimulating factor (GM-CSF).

Methods
Patients with R/M HNSCC refractory to at least first-line therapy and for whom palliative RT is clinically indicated received cemiplimab plus RT, cyclophosphamide, and GM-CSF. The co-primary objectives were the safety, tolerability, and efficacy of cemiplimab plus RT, cyclophosphamide, and GM-CSF in 15 patients with R/M HNSCC.

Results
Fifteen patients were enrolled. Patients discontinued treatment due to progression of disease. The most common treatment-emergent adverse events (TEAEs) of any grade were fatigue (40.0%), constipation (26.7%), and asthenia, dyspnea, maculo-papular rash, and pneumonia (each 20%). The only grade ≥3 TEAE that occurred in two patients was pneumonia (13.3%). By investigator assessment, there was one partial response (6.7%); disease control rate was 40.0% (95% confidence interval [CI], 16.3–67.7; five patients with stable disease); seven patients had progressive disease, and two were not evaluable. Median progression-free survival by investigator assessment was 1.8 months (95% CI, 1.7–4.7).

Conclusion
The regimen demonstrated tolerability but not efficacy above that which can be achieved with anti–PD-1 inhibitor monotherapy for R/M HNSCC.
Switching the Inhibitor‐Enzyme Recognition Profile via Chimeric Carbonic Anhydrase XII
Authors: Smirnovienė Joana , Smirnov Alexey , Zakšauskas Audrius , Zubrienė Asta , Petrauskas Vytautas , Mickevičiūtė Aurelija , Michailovienė Vilma , Čapkauskaitė Edita , Manakova Elena , Gražulis Saulius , Baranauskienė Lina , Chen Wen‐Yih , Ladbury John E. , Matulis Daumantas 
Published: May 2021

AbstractA key part of the optimization of small molecules in pharmaceutical inhibitor development is to vary the molecular design to enhance complementarity of chemical features of the compound with the positioning of amino acids in the active site of a target enzyme. Typically this involves iterations of synthesis, to modify the compound, and biophysical assay, to assess the outcomes. Selective targeting of the anti‐cancer carbonic anhydrase isoform XII (CA XII), this process is challenging because the overall fold is very similar across the twelve CA isoforms. To enhance drug development for CA XII we used a reverse engineering approach where mutation of the key six amino acids in the active site of human CA XII into the CA II isoform was performed to provide a protein chimera (chCA XII) which is amenable to structure‐based compound optimization. Through determination of structural detail and affinity measurement of the interaction with over 60 compounds we observed that the compounds that bound CA XII more strongly than CA II, switched their preference and bound more strongly to the engineered chimera, chCA XII, based on CA II, but containing the 6 key amino acids from CA XII, behaved as CA XII in its compound recognition profile. The structures of the compounds in the chimeric active site also resembled those determined for complexes with CA XII, hence validating this protein engineering approach in the development of new inhibitors.
Development and optimization of high‐performance PEEK/CF/Nanosilica hybrid composites
Authors: Lin Leyu , Schlarb Alois K. 
Published: May 2021

In the present study, tribological properties of PEEK/CF/nanosilica composites with distinct amounts of silica nanoparticles against steel were studied by using a block‐on‐ring tribometer followed by the characterizations of associated transfer films and polymer worn surfaces. The results demonstrate that the content of silica nanoparticles exerts an obvious influence on the friction and wear properties of PEEK/CF/nanosilica composites. Under low‐load conditions, the friction coefficient and specific wear rate exhibit opposite dependence on the nanosilica content. The friction coefficient decreases with increasing nanofiller content, while the specific wear rate increases with enhancing nanosilica loading. When the load conditions were changed toward high values, the divergence of the tribological properties becomes insignificant, which show less dependence on the nanosilica loading. Taking into account the practical applications of such composites, the composite containing 2 wt.% silica nanoparticles can serve as an excellent candidate for manufacturing tribological components in the practical applications.
Diurnal variations in the thickness of the inner bark of tree trunks in relation to xylem water potential and phloem turgor
Authors: Epron Daniel , Kamakura Mai , Azuma Wakana , Dannoura Masako , Kosugi Yoshiko 
Published: May 2021

Why this research MattersThe inner bark plays important roles in tree stems, including radial exchange of water with the xylem and translocation of carbohydrates. Both processes affect the water content and the thickness of the inner bark on a diurnal basis. For the first time, we simultaneously measured the diurnal variations in the inner bark thickness of hinoki cypress (Chamaecyparis obtusa) by using point dendrometers and those of local xylem potential by using stem psychrometers located next to the dendrometers to determine how these variations were related to each other, to phloem turgor and carbohydrate transport. We also estimated the axial hydrostatic pressure gradient by measuring the osmolality of the sap extracted from the inner bark. The inner bark shrunk during the day and swelled during the night with an amplitude related to day‐to‐day and seasonal variations in climate. The relationship between changes in xylem water potential and inner bark thickness exhibited a hysteresis loop during the day with a median lag of 2 h. A phloem turgor‐related signal can be retrieved from the diurnal variations in the inner bark thickness, which was higher at the upper than at the lower position along the trunk. However, a downward hydrostatic pressure gradient was only observed at dawn, suggesting diurnal variations in the phloem sap flow velocity.
TT genotype of the MMP‐9‐1562C/T polymorphism may be a risk factor for thrombolytic therapy‐induced hemorrhagic complications after acute ischemic stroke
Authors: Dusanovic Pjevic Marija , Jekic Biljana , Beslac Bumbasirevic Ljiljana , Vojvodic Ljubica , Damnjanovic Tatjana , Grk Milka , Maksimovic Nela , Pesic Milica , Gulic Milica , Trickovic Jelena , Kacar Katarina 
Published: May 2021

AbstractIntroductionLevels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) influence recombinant tissue plasminogen activator (rtPA) therapy response in patients with acute ischemic stroke (AIS). Serum levels of MMPs and TIMPs along with the expression of genes coding these proteins are related to the recovery and appearance of adverse effects (AE) after AIS. Consequently, it is important to explore whether polymorphisms in regulatory sequences of MMPs and TIMPs are associated with rtPA response in AIS patients.ObjectivesTo determine whether selected polymorphic variants within MMP‐2, MMP‐9, and TIMP‐2 genes may influence rtPA therapy response with regard to outcomes in patients with AIS and the occurrence of AE.MethodsOur study included 166 patients suffering AIS, treated with rtPA. Patients’ recovery was estimated using the Modified Rankin Scale (mRS) 3 months after the AIS occurred. Favorable outcome was defined with scores 0–1 and poor outcome with scores 2–6. Genotyping was performed using real‐time PCR (rs243866, rs243865, rs243864, rs2277698, and rs8179090) and PCR‐RFLP (rs2285053, rs3918242) methods. Additionally, rtPA AE were followed during the hospitalization.ResultsThere was no significant association between genotypes and alleles of selected polymorphisms and rtPA therapy response measured through the decrease of the mRS score in patients with AIS. Intracranial hemorrhage, as well as parenchymal hematoma type 2, was significantly more frequent in patients with TT genotype of the MMP‐9‐1562C/T polymorphism (p = 0.047, p = 0.011, respectively). Patients with intracranial hemorrhages after rtPA were significantly more likely to have the TT genotype of TIMP‐2‐303C/T polymorphism and the TT genotype of MMP‐9‐1562C/T polymorphism (p < 0.001).ConclusionTT genotype of the MMP‐9‐1562C/T polymorphism may be a risk factor for rtPA‐induced hemorrhagic complications after AIS.
Von der LED bis zur laserbasierten Lichtquelle
Authors: Brümmer Mathias , Hartwig Ulrich 
Published: May 2021

ZusammenfassungProjektionssysteme erfordern Lichtquellen mit kleiner Étendue und hoher Leuchtdichte. Diese Anforderungen werden von Hochdruck‐Entladungslampen, LEDs und laserbasierten Lichtquellen erfüllt. Hochdruck‐Entladungslampen erzielen höchste Leuchtdichten. Sie sind preiswert und finden noch immer in lichtstarken Videoprojektoren verbreitet Anwendung. Die Leuchtdichte moderner Dünnfilm‐LEDs ist ausreichend, um kleinere Endoskope, Bühnenscheinwerfer oder Kleinprojektoren effizient zu betreiben. Lichtquellen mit Laserdioden überschreiten die Leuchtdichte von Entladungslampen, können aber aus Sicherheitsgründen direkt nur bei geringer Strahlungsleistung betrieben werden. LARP‐Lichtquellen wandeln das Laserlicht über einen Leuchtstoff in normales Licht um. Damit sind sie hell genug, um Hochdruck‐Entladungslampen zu ersetzen. Sie sind allerdings noch sehr teuer. Deshalb finden sie zurzeit vor allem in High‐End‐Geräten und Autoscheinwerfern im Premiumbereich Anwendung.
Bose‐Einstein‐Kondensat aus Exzitonen?
Authors: Wurstbauer Ursula , Holleitner Alexander W. 
Published: May 2021

ZusammenfassungZweidimensionale (2D) Kristalle zeigen verstärkt Vielteilchenphänomene, was sie für Forschung und Anwendungen interessant macht. Dafür sorgt die viel geringere Abschirmung der Ladungsträger im Vergleich zum dreidimensionalen Fall. Verantwortlich dafür sind die Flachheit des Materials, die dieelektrische Umgebung und mit der reduzierten Dimensionalität verbundene Quanteneinschränkungen. 2D‐Kristalle können zudem aufeinander gestapelt werden, wobei die einzelnen Schichten nur durch Van‐der‐Waals‐Kräfte verbunden sind. Solche künstlichen Van‐der‐Waals‐Kristalle erlauben die Realisierung einer Fülle von neuartigen physikalischen Systemen. In halbleitenden Heterostrukturen gelang es nun, erste Hinweise für ein optisch generiertes Bose‐Einstein‐Kondensat von Exzitonen zu finden.
Das hölzerne Gelächter
Authors: Mathelitsch Leopold , Verovnik Ivo 
Published: May 2021

ZusammenfassungEin Spielzeug‐Xylophon ist meist das erste Instrument unserer Kindheit – wenn auch mit Metallplättchen als Klangerzeuger. Dabei bedeutet das Wort Xylophon im Griechischen „Holzklang“. Xylophone und Marimbas gab es bereits in der Antike. Instrumente mit Metallplättchen zeigen ein signifikant anderes Schwingungsverhalten als solche mit Holzplättchen. Deren Klang lässt sich durch Feilen an den richtigen Stellen in einem weiten Bereich abstimmen.
Pain burden in children with cerebral palsy (CPPain) survey: Study protocol
Authors: Andersen Randi Dovland , Genik Lara , Alriksson‐Schmidt Ann I. , Anderzen‐Carlsson Agneta , Burkitt Chantel , Bruflot Sindre K. , Chambers Christine T. , Jahnsen Reidun B. , Jeglinsky‐Kankainen Ira , Kildal Olav Aga , Ramstad Kjersti , Sheriko Jordan , Symons Frank J. , Wallin Lars , Andersen Guro L. 
Published: May 2021

AbstractPain is a significant health concern for children living with cerebral palsy (CP). There are no population‐level or large‐scale multi‐national datasets using common measures characterizing pain experience and interference (ie, pain burden) and management practices for children with CP. The aim of the CPPain survey is to generate a comprehensive understanding of pain burden and current management of pain to change clinical practice in CP. The CPPain survey is a comprehensive cross‐sectional study. Researchers plan to recruit approximately 1400 children with CP (primary participants) across several countries over 6‐12 months using multimodal recruitment strategies. Data will be collected from parents or guardians of children with CP (0‐17 years) and from children with CP (8‐17 years) who are able to self‐report. Siblings (12‐17 years) will be invited to participate as controls. The CPPain survey consists of previously validated and study‐specific questionnaires addressing demographic and diagnostic information, pain experience, pain management, pain interference, pain coping, activity and participation in everyday life, nutritional status, mental health, health‐related quality of life, and the effect of the COVID‐19 pandemic on pain and access to pain care. The survey will be distributed primarily online. Data will be analyzed using appropriate statistical methods for comparing groups. Stratification will be used to investigate subgroups, and analyses will be adjusted for appropriate sociodemographic variables. The Norwegian Regional Committee for Medical and Health Research Ethics and the Research Ethics Board at the University of Minnesota in USA have approved the study. Ethics approval in Canada, Sweden, and Finland is pending. In addition to dissemination through peer‐reviewed journals and conferences, findings will be communicated through the CPPain Web site (www.sthf.no/cppain), Web sites directed toward users or clinicians, social media, special interest groups, stakeholder engagement activities, articles in user organization journals, and presentations in public media.