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Brakemeier, Eva-Lotta. "Nachruf auf Hubert Feger". Psychologische Rundschau 74, n. 4 (ottobre 2023): 245–46. http://dx.doi.org/10.1026/0033-3042/a000652.
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Milyutin, Vasily, Zuzana Birčáková, Mária Fáberová, Radovan Bureš, Peter Kollár e Ján Füzer. "Effect of Rare-Earth Doping on Dynamic Magnetic Properties of FeGa Alloy". Materials Science Forum 1081 (24 marzo 2023): 149–54. http://dx.doi.org/10.4028/p-97z6qj.
Testo completoAbstract (sommario):
The magnetization process at elevated frequencies (up to 15 kHz) of ring-shaped binary Fe81Ga19 alloy was studied. Frequency and magnetic field dependences of coercive field and remanent induction were analyzed. Hysteresis loops and initial permeability were studied at low (200 Hz) and high (15 kHz) frequencies. The same measurements were made for FeGaRE alloys to establish the effect of rare-earth elements on dynamic magnetic properties.
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Koklic, Tilen, Rima Chattopadhyay, Rinku Majumder e Barry R. Lentz. "Factor Xa dimerization competes with prothrombinase complex formation on platelet-like membrane surfaces". Biochemical Journal 467, n. 1 (20 marzo 2015): 37–46. http://dx.doi.org/10.1042/bj20141177.
Testo completoAbstract (sommario):
Exposure of phosphatidylserine (PS) molecules on activated platelet membrane surface is a crucial event in blood coagulation. Binding of PS to specific sites on factor Xa (fXa) and factor Va (fVa) promotes their assembly into a complex that enhances proteolysis of prothrombin by approximately 105. Recent studies demonstrate that both soluble PS and PS-containing model membranes promote formation of inactive fXa dimers at 5 mM Ca2+. In the present study, we show how competition between fXa dimerization and prothrombinase formation depends on Ca2+ and lipid membrane concentrations. We used homo-FRET measurements between fluorescein–E–G–R–chloromethylketone (CK)–Xa [fXa irreversibly inactivated by alkylation of the active site histidine residue with FEGR (FEGR–fXa)] and prothrombinase activity measurements to reveal the balance between fXa dimer formation and fXa–fVa complex formation. Changes in FEGR–fXa dimer homo-FRET with addition of fVa to model-membrane-bound FEGR–fXa unambiguously demonstrated that formation of the FEGR–fXa–fVa complex dissociated the dimer. Quantitative global analysis according to a model for protein interaction equilibria on a surface provided an estimate of a surface constant for fXa dimer dissociation (KfXa×fXad, σ) approximately 10-fold lower than KfXa×fVad,σ for fXa–fVa complex. Experiments performed using activated platelet-derived microparticles (MPs) showed that competition between fXa dimerization and fXa–fVa complex formation was even more prominent on MPs. In summary, at Ca2+ concentrations found in the maturing platelet plug (2–5 mM), fVa can compete fXa off of inactive fXa dimers to significantly amplify thrombin production, both because it releases dimer inhibition and because of its well-known cofactor activity. This suggests a hitherto unanticipated mechanism by which PS-exposing platelet membranes can regulate amplification and propagation of blood coagulation.
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Ulshöfer, Kuno, e Kommission für Geschichtliche Landeskunde In Baden-Württemberg. "Rezension von: Kommission für Geschichtliche Landeskunde in Baden-Württemberg (Hrsg.), Schwäbische Chroniken der Stauferzeit". Württembergisch Franken 64 (4 marzo 2024): 299. http://dx.doi.org/10.53458/wfr.v64i.10704.
Testo completoAbstract (sommario):
Schwäbische Chroniken der Stauferzeit. Hrsg. von der Kommission für geschichtliche Landeskunde in Baden-Württemberg. Sigmaringen: Thorbecke. 1. Historia Weiforum. Neu hrsg., übers, u. erl. von Erich König. 1978 (Nachdr. d. Ausg. 1938) 28, 154 S.. 2. Die Zwiefalter Chroniken Ortliebs und Bertholds. Neu hrsg., übers, u. erl. von Luitpold Wallach, Erich König und Karl Otto Müller. 1978 (Nachdr. d. Ausg. 1941) 16, 60, 385 S.. 3. Die Chronik des Klosters Petershausen. Neu hrsg. u. übers, von Otto Feger. 1978 (Nachdr. d. Ausg. 1956) 276 S.
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Fedorov, Yury A., Darya F. Kostenko e Irina V. Dotsenko. "Behavior of Nickel's Migration Forms in Water Along the Continuum “The Mius River's Estuary - the Taganrog Bay of the Azov Sea”". UNIVERSITY NEWS. NORTH-CAUCASIAN REGION. NATURAL SCIENCES SERIES, n. 4-2 (216-2) (18 gennaio 2023): 77–89. http://dx.doi.org/10.18522/1026-2237-2022-4-2-77-89.
Testo completoAbstract (sommario):
The studys results of nickel (Ni) migration forms in water along the continuum “the Mius River estuary - the Taganrog Bay of the Azov Sea” are presented. Standard methods, specialized equipment and mathematical and statistical analysis were applied. It is revealed that experimental data on the content of the nickel dissolved form do not exceed global background concentrations. The nickel suspended migration form with dominant values in the Mius River zone (54-71 % of the gross content) prevailed along the continuum. A symbiotic behavior was established for all Ni migration forms with a general decrease in concentrations along the profile of “the Mius River→the Taganrog Bay”. A correlation analysis was carried out between the contents of Nigr., Nidis., Nisusp., Nisusp. in % of the total and physical and chemical parameters, as well as various forms of iron. The significance level of p≥0.05 was noted in the pair S (‰) and Nigr., Nidis., Nisusp., and moderate direct connections are characteristic of the pairs Ni susp. in % of the total – Fegr., Nigr. – Fesusp. in % of Fegr. and Nisusp. in % of the total – Fesusp. in % of Fegr.. With a sub-parallel decrease in these indicators, the withdrawal of both nickel and iron into the bottom sediments was recorded.
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Al-Aizari, Ahmed Ali, Yaser Hassan Dewir, Rashid Sultan Al-Obeed, Adel M. Al-Saif, Khalid F. Almutairi, Hosakatte Niranjana Murthy e Mansor Hakiman. "Study of Shoot Tip Necrosis Problems of Fegra Fig (Ficus palmata Forssk.) In Vitro in Saudi Arabia". HortScience 59, n. 8 (agosto 2024): 1127–32. http://dx.doi.org/10.21273/hortsci17765-24.
Testo completoAbstract (sommario):
This work studied the micropropagation of fegra fig (F. palmata Forssk.) during which we experienced the incidence of shoot-tip necrosis (STN). STN was evident during the shoot elongation stage, which was regenerated on Murashige and Skoog (MS) medium supplemented with 2 mg/L 6-benzylaminopurine. To alleviate SNT, we conducted a series of experiments and supplemented the medium with calcium chloride (40, 80, and 120 mg/L), ascorbic acid (50, 100, and 150 mg/L), silver nitrate (1, 2, and 3 mg/L), and boric acid (9.3, 12.4, and 15.5 mg/L). Results showed that all the treatments controlled STN at varying levels, and supplementation of medium with 3 mg/L silver nitrate reduced the incidence of STN from 80% to 24%. The regenerated shoots were rooted on the same medium with incubation of cultures in the dark for 3 weeks and subsequent 4 weeks of incubation under 16/8-hour light/dark photoperiod. The growth parameters (number of shoots and roots, length of the main shoot and root, fresh and dry weights), photosynthetic pigments (chlorophylls and carotenoids), and relative water content of plantlets were restored with the application of 3 mg/L silver nitrate to the medium. Incubation of cultures initially in the dark followed by 16/8-hour light incubation facilitated axillary shoot elongation. On the basis of our findings, it is recommended to culture the regenerated axillary shoots of fegra fig onto MS medium containing 3% sucrose, 1.5 mg/L activated charcoal, and 3 mg/L silver nitrate to manage STN effectively.
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Birčáková, Zuzana, Vasily Milyutin, Peter Kollár, Mária Fáberová, Radovan Bureš, Ján Füzer, Miroslav Neslušan, Serhii Vorobiov e Marianna Batkova. "Magnetic characteristics and core loss separation in magnetostrictive FeGa and FeGaRE (RE = Tb, Y) alloys". Intermetallics 151 (dicembre 2022): 107744. http://dx.doi.org/10.1016/j.intermet.2022.107744.
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Zúñiga Ugalde, Felipe. "Essential of Soil Science: Soil Formation, Functions, Use and Classification (World Reference Base, WRB). 2018. Borntraeger Science Publishers, Stuttgart, Germany. 171 p. (101 figuras, 22 tablas)." Agro sur 47, n. 1 (30 aprile 2019): 3–4. http://dx.doi.org/10.4206/agrosur.2019.v47n1-02.
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Este libro, corresponde a una traducción en inglés del texto de "Bodenkunde in Stichworten” publicado por primera vez en 1969 por el Prof. Diedrich Schröder, en Kiel (Schlichting, 1970) quien lo actualizó hasta su fallecimiento en 1988. En 1992, el profesor Winfried E. H. Blum (BOKU, Viena) retoma esta meritoria tarea publicando la 5.a edición de este libro (Stahr, 1993; Feger, 2007) hasta su 7.a edición en 2012. La presente versión en inglés se divide en nueve capítulos. La introducción es breve, pero muy clara respecto a las funciones y la importancia del suelo. En los ...
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Berrier-Lucas, Celine, e Charlène Arnaud. "Éditorial. Les Communs : un éclairage réflexif". Revue de l’organisation responsable Vol. 19, n. 2 (2 luglio 2024): 3–9. http://dx.doi.org/10.3917/ror.192.0003.
Testo completoAbstract (sommario):
Cet essai se propose de contribuer à l’appel lancé par Philippe Eynaud, Clément Feger et Corinne Vercher-Chaptal (2024), dans leur article introductif de ce numéro spécial, de considérer les « angles morts » de la recherche contemporaine sur les communs. Nous mobilisons les approches critiques en management afin de mettre en lumière la face sombre des communs, les communs négatifs (Mies & Bennholdt-Thomsen, 2001 ; Monnin, 2021), qui dans le contexte actuel de crises socio-écologiques et d’injustices prolifèrent (Tsing, 2015b). Cette critique prometteuse – et à travers elle, cet essai – constitue ainsi une invite à politiser les communs négatifs comme constitutifs du capitalisme moderne.
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Abdelrahim, Ahmed M., Muhammad G. Abd El-Moghny e Mohamed S. El-Deab. "In situ generation of exfoliated graphene layers on recycled graphite rods for enhanced capacitive performance of Ni–Co binary hydroxide". RSC Advances 11, n. 42 (2021): 26258–72. http://dx.doi.org/10.1039/d1ra03954g.
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A functionalized exfoliated graphite rod (FEGR), with a high surface area, is produced for use as a promising substrate for supercapacitors, via controlled oxidative treatment of a recycled graphite rod of exhausted zinc–carbon batteries.
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Drewelow, Horst. "Giftedness — More Than IQ". Gifted Education International 13, n. 2 (settembre 1998): 136–39. http://dx.doi.org/10.1177/026142949801300206.
Testo completoAbstract (sommario):
There is no doubt about the assertion that high intellectual abilities of different kinds play a substantial role in conceptions of giftedness. At the same time most researchers in theory agree that giftedness is not identical with high intelligence. An analysis of literature though is reflecting a different picture (Bartenswerfer, 1990, Feger, 1990; Carter & Swanson, 1990; Heller & Menacher, 1992; Rogers, 1989): Wherever giftedness is discussed, nothing but intellectual giftedness is meant. In many publications we find IQ scores, with differing cut-off-levels of 125, 130, 140, 150 points, as the only indicators for giftedness. Such an “IQ-diagnosis” has found many critics within research on gifted education.
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Maier, Anna, Janina Bittner, Jörg M. Fegert e Ulrike Hoffmann. "Sensibilisierung für (sexualisierte) Gewalt in der Jugendarbeit". deutsche jugend, n. 12 (9 dicembre 2022): 530–39. http://dx.doi.org/10.3262/dj2212530.
Testo completoAbstract (sommario):
Mit sexualisierter Gewalt gegen Kinder und Jugendliche und der Frage, wie man Mitarbeiterinnen und Mitarbeiter in der Jugendarbeit dafür sensibilisieren kann, befassen sich Anna Maier, Janina Bittner, Jörg M. Fegert und Ulrike Hoffmann in diesem Beitrag. Sie weisen darauf hin, dass es bei solchen Delikten nach wie vor eine erhebliche Dunkelziffer gibt. Viele Fälle von sexualisierter Gewalt werden nicht erkannt; die Betroffenen schweigen jahrelang aus Gründen wie Scham oder sozialem Druck. Weil etwa die Hälfte der Ehrenamtlichen in Deutschland regelmäßig mit Kindern und Jugendlichen arbeitet, konzentrieren sich die Autor/inn/en auf den ehrenamtlichen Bereich. Sie zeigen auf, wie Ehrenamtliche sexualisierter Gewalt auf die Spur kommen können; sie stellen die Risikokonstellationen, aber auch Schutzfaktoren dar und erklären, wie Schutzkonzepte in Einrichtungen und Organisationen der Jugendarbeit auf den Weg gebracht werden können und wie bei einem Verdachtsfall vorgegangen werden kann. Hingewiesen wird schließlich auf eine Fortbildungs- und Informationsplattform zur Sensibilisierung für Gefährdungsfaktoren, die an der Klinik für Kinder- und Jugendpsychiatrie des Uniklinikums Ulm entwickelt worden ist.
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Kazumori, H., A. Yamada, M. Mita, T. Nokuo e M. Saito. "Field Emission SEM with a Newly Developed FEGUN and Conical Strongly Excited Objective Lens". Microscopy and Microanalysis 6, S2 (agosto 2000): 764–65. http://dx.doi.org/10.1017/s143192760003631x.
Testo completoAbstract (sommario):
A newly developed cold FE-GUN which enables to us to obtain large probe current and low emission noise, and conical strongly excited objective lens has been installed on the JSM-6700F Scanning Electron Microscope (SEM). In the range of accelerating voltages from 0.5 to 15kV, this instrument has got much better resolution as compared with in-lens type SEM (Ohyama et al 1986)(Fig. 1). We can obtain high-resolution secondary electron images with large samples (ex. 150mm ϕ×10mmH).Our old type objective lens (Kazumori et al 1994) has the limitation of working distance (WD), but the new lens enables us to work at very short WD at accelerating voltage of 15kV. As a result the spherical (Cs) and chromatic (Cc) aberration constants are 1.9mm and 1.7mm respectively at a WD of 3mm.In order to get large probe current, we increased emission current and got near the distance between the t ip of emi tter and the pr inciple plane of condenser lens.
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Adityo, Rayno Dwi. "Studi Normatif Legalitas Peran Tokoh Masyarakat Dalam Undang-Undang No. 7 Tahun 2012 Tentang Penanganan Konflik Sosial". JURNAL MAHKAMAH 2, n. 1 (31 luglio 2017): 1. http://dx.doi.org/10.25217/jm.v2i1.102.
Testo completoAbstract (sommario):
Currently indonesia often torn asunder with different kinds of events which is quite disturbing national stability start of the disintegration by separatist group and other’s. It is something that can be easy occur given indonesia is a archipelago state, so in controlled requires strength tight from own society or the state of directly. With the diversity of social conflict tribal often law ineffective so that we consider that the need for the role of an instrument informal as community figures, traditional leaders and religion figures that more actively in acktivity has purpose for making stability the condition from social conflict.
This research, writter trying to give some description that is the participation from community, traditional leaders and religion figures most important for resolving the conflict and as the law in Indonesian that participation this fegures had tranformation from unformal side to formal side as the UU No. 7 Tahun 2012 Tentang Penanganan Konflik Sosial mandating.
Key Words: Law, to respon, community figures, formal and unformal.
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Setyawan, Wahyu Beny Mukti, e Fery Dona. "E-INTEGRATIVE CONTROL SYSTEM AS A COMMUNITY ORGANIZATION SUPERVISION DESIGN TO REALIZE THE CONCEPT OF STATE". Jurnal Hukum 36, n. 2 (19 settembre 2020): 117. http://dx.doi.org/10.26532/jh.v36i2.11390.
Testo completoAbstract (sommario):
The government, as the party that has the mandate from the people tosa feguar ditsso vereignty, has revoked permits for the establish men to social organizations which are deemed contrary to the ideology of the State. The Ministryof Law and Human Rights as the party that grants the permit can immediately revokethelicense on the basis of the contractus actus principle contained in the Perppu No. 2 of 2017 concerning Amendmentsto Law No. 17 of 2013 concerning Community Organization. Even though they have taken repressive steps, the Ministry of Law and Human Rights has not taken any preventiveaction in obstructing and preventing theemergence of social organizations that are contrary to the ideology of the State. There fore the authors providean effective solution in theformofan E-Integrative Control System as a Social Organization Supervision Design to Realize the Concept of State Sovereignty so that the Government as the party responsible for granting perm its for the establish men to social organizations and contradicting stateideology. Which could threaten theso vereigntyandintegrity of the Unitary State of the Republic of Indonesia.
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Nashawi, Fatimah A., Hani Y. Abdullah, Nahlaa A. Khalifa, Ibrahim A. Alzahrani e Ahmed A. Al-Ghamdi. "Effect of Different Saudi Honey Types Mixed with Natural Substances on Some Bacterial Strains". Journal of King Abdulaziz University - Medical Sciences 24, n. 1 (31 marzo 2017): 23–31. http://dx.doi.org/10.4197/med.24-1.3.
Testo completoAbstract (sommario):
To evaluate the antibacterial eff ects of three types of Saudi honey (Feghra, Sider and Natural honey) alone and mixed with ginger or lemon in comparison to Manuka honey as a potential natural antibacterial agent. Saudi honeys were evaluated against five types of bacterial strains; Klebsiella pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, Haemophilus influenzae and Streptococcus pneumoniae. Chocolate agars were prepared first with different concentrations of each type of honey, and then with specific concentrations either of ginger or lemon added to honey. Bacterial species were inoculated on each agar and incubated at 37oC in a CO2 incubator overnight. Significant differences were found between diff erent types of honey and different concentrations of the same honey on bacterial growth. There are no significant differences and synergistic effects when adding ginger to diff erent honey types. Addition of lemon show significant differences and good synergistic effects against all tested bacterial species except Klebsiella pneumoniae and Staphylococcus aureus at 15 and 20% honey concentration. In conclusion, antibacterial effects of different types of honey are type and concentration dependent. Adding lemon to the different types of honey changes the pH and acidity and increases the honey’s antibacterial effect.
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Feldshtein, Eugene E., Larisa N. Dyachkova e Justyna Patalas-Maliszewska. "On Investigating the Microstructural, Mechanical, and Tribological Properties of Hybrid FeGr1/SiC/Gr Metal Matrix Composites". Materials 14, n. 1 (1 gennaio 2021): 174. http://dx.doi.org/10.3390/ma14010174.
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In recent years, studies of different properties of hybrid metal matrix composites, as well as very detailed issues, have been published. In this article, ready-made iron, graphite, and silicon carbide powders were used to produce the base material and composites. An analysis of some microstructural and mechanical properties, as well as the tribological behavior of metal matrix composites (MMCs), based on FeGr1 sintered material with the single and hybrid addition of a silicon carbide and graphite was undertaken. During the study, the flexural and compressive strength of MMCs were analyzed and changes of the momentary coefficient of friction, the temperature of friction, as well as wear rates of the MMCs tested were monitored. Based on the results, it was revealed that wear rates decreased 12-fold in comparison to the base material when SiC or SiC + Gr were added. Further research into MMCs with ceramic particle additives is proposed.
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Baureithel, Ulrike. "Buchrezension Aufarbeitung des sexuellen Kindesmissbrauchs in Deutschland, hgg. v. Jörg M. Fegert, Trauma & Gewalt, Heft 02, Klett-Cotta 2011". Sexuologie. Zeitschrift für Sexualmedizin, Sexualtherapie und Sexualwissenschaft 18, n. 34 (dicembre 2011): 213–15. http://dx.doi.org/10.61387/s.2011.34.24.
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Baloga, Martin. "Constitutiones Synodales Ecclesiae Strigoniensis". Notitiae Historiae Ecclesiasticae 12, n. 2 (2023): 43–53. http://dx.doi.org/10.54937/nhe.2023.12.2.43-53.
Testo completoAbstract (sommario):
In 1493, the Ostrihom Synod was held. It resulted in the document Constitutiones Synodales Ecclesiae Strigoniensis printed in 1494 in Vienna. However, this print was not available to historians for many centuries. In the middle of the 20th century, two specimens were identified. One defective copy of the print is located in Zagreb, and the other one, the only complete copy, is stored in SNK in Martin. The publisher is Theobald Feger and the printer is Johann Winterburger. The press contains several regulations concerning the area of church life. The printed text contains 37 canons of the synod and liturgical calendar. The presented unique item is a part of the envelope and its bookbinding originates from the 19th century. The owner was the Franciscan order in Bratislava, which owned one of the largest libraries in Hungary. Further research of incunabula connected to the territory of Hungary may reveal more similarly rare documents.
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Chattopadhyay, Rima, Tilen Koklic e Barry Lentz. "Factor Xa Dimerization and Prothrombinase Complex Formation Are Competitive Process On a Membrane Surface." Blood 114, n. 22 (20 novembre 2009): 2123. http://dx.doi.org/10.1182/blood.v114.22.2123.2123.
Testo completoAbstract (sommario):
Abstract Abstract 2123 Poster Board II-100 Exposure of phosphatidylserine (PS) molecules on activated platelet membranes is a crucial event in blood coagulation. Binding of PS to a specific site on factors Xa and on Va promotes prothrombinase assembly and enhances proteolytic activity of factor Xa. PS binding produces significant structural changes in both proteins. Recent studies demonstrate formation of inactive Xa dimer by both soluble, short-chain PS and PS-containing membranes at high Ca+2 concentration (Chattopadhyay et al.,2009, Biophys. J, 974). Association of factor Xa with factor Va in the presence of soluble PS relieves this inactivation. From kinetic measurements, we found that apparent Kd's for the Xa-Va interaction in the presence of 50 mM PS/PC (25/75) membranes increased in with increasing factor Xa concentrations, suggesting that factor Va must compete with factor Xa dimer in order to form the Xa-Va complex on the membrane surface. The fluorescence anisotropy of active site labeled factor Xa, FEGR (Fluorescein-GLU-GLY-ARG-chloromethylketone)-Xa, is lowered in the presence of PS membrane on which it forms dimer (Koklic et al., October 2009, Biophys. J., V-97, Issue 8) We report now that addition of factor Va to FEGR-Xa/membrane samples produced a saturating increase in anisotropy, clearly indicating that factor Va competed with factor Xa dimer formation. This experiment was repeated for several Ca2+ concentrations and yielded increasing apparent Kd's for Xa-Va interaction with increasing Ca2+concentration. FEGR-Xa fluorescence anisotropy as well as DEGR-Xa (factor Xa labeled at the active site with Dansyl-GLU-GLY-ARG-chloromethylketone) fluorescence intensity at varying membrane and factor Va concentrations for both 23 nm and 120 nm vesicles were analyzed globally to obtain surface Kd's of dimerization and factor Va-factor Xa interaction. This showed that membrane discreteness (slow distribution of factor Xa between discrete membrane vesicles) had almost no effect on the competition between factor Xa dimer formation and Xa-Va complex formation. We conclude that prothrombinase complex formation can overcome PS-induced factor Xa inhibition through factor Xa dimer formation at Ca2+ concentrations just above plasma concentration. In this way, one can imagine that factor Va is required to overcome factor Xa dimerization and amplify thrombin production in the early platelet plug. Supported by USPHS grant HL072827 to BRL. Disclosures: No relevant conflicts of interest to declare.
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Berghahn, K. L. "Poetische Vernunft. Moral und Asthetik im Deutschen Idealismus. Von Hans Feger. Stuttgart: Metzler, 2007. 630 Seiten. 79,95." Monatshefte 101, n. 2 (1 giugno 2009): 275–79. http://dx.doi.org/10.1353/mon.0.0118.
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Królczyk, Grzegorz, Eugene Feldshtein, Larisa Dyachkova, Mariusz Michalski, Tomasz Baranowski e Roman Chudy. "On the Microstructure, Strength, Fracture, and Tribological Properties of Iron-Based MMCs with Addition of Mixed Carbide Nanoparticulates". Materials 13, n. 13 (27 giugno 2020): 2892. http://dx.doi.org/10.3390/ma13132892.
Testo completoAbstract (sommario):
In this paper, the features of the strength, fractures, and tribological behavior of metal-matrix composites based on the FeGr1 material are discussed. To improve the material properties, a mixture of SiC, Al2O3 and C nanoparticulates have been added to an iron-based matrix. The simplex lattice design method and hardness, compression, and bending tests were used to determine the mechanical properties. Scanning electron microscopy was applied for fracture features analysis. Different fracture types, mainly trans-crystalline quasi-brittle and brittle fracture or inter-granular fracture and microcracks were registered for the composites tested. Depending on the type and amount of ceramic additives, significant changes in strength, as well as in the fracture features of the metal-matrix composites (MMCs), were observed. Based on tribological tests, changes in the momentary coefficients of friction, temperature of the friction surface, and wear rate of the composites with nanoparticulates were described. An analysis of the worn surface morphology revealed changes in the wear process depending on the MMC composition. It was shown that the use of hybrid mixed additives based on hard ceramic nanoparticulates improved both strength and tribological properties of composites.
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Tesoro, Giuliana. "Advances in polyimide science and technology, C. Feger and M. M. Khojasteh, Eds., M/S/Htoo technomic publishing, 1993". Journal of Polymer Science Part A: Polymer Chemistry 31, n. 13 (dicembre 1993): 3501. http://dx.doi.org/10.1002/pola.1993.080311343.
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Al-Aizari, Ahmed Ali, Yaser Hassan Dewir, Abdel-Halim Ghazy, Abdullah Al-Doss e Rashid Sultan Al-Obeed. "Micropropagation and Genetic Fidelity of Fegra Fig (Ficus palmata Forssk.) and Grafting Compatibility of the Regenerated Plants with Ficus carica". Plants 13, n. 9 (6 maggio 2024): 1278. http://dx.doi.org/10.3390/plants13091278.
Testo completoAbstract (sommario):
Ficus palmata is an important fig species that produces edible and nutritious fruit and possesses several therapeutic uses. This study reports an effective method for the micropropagation of F. palmata using nodal explants. In vitro shoots were cultured for 7 weeks onto MS medium fortified with different concentrations of cytokinins, light intensities, sucrose concentrations, and light/dark incubation treatments. Optimal axillary shoot proliferation (10.9 shoots per explant) was obtained on a medium containing 30 g/L sucrose and supplemented with 2 mg/L 6-benzylaminopurine (BAP) under 35 μmol/m2/s light intensity. Dark incubation limited the foliage growth but favored shoot elongation and rooting compared with light incubation. Elongated shoots, under dark conditions, were rooted (100%; 6.67 roots per explant) onto MS medium containing 1 mg/L indole-3-acetic acid (IAA) and 1.5 g/L activated charcoal. The micropropagated plantlets were acclimatized with a 95% survival rate. In this study, the genetic fidelity of micropropagated F. palmata clones along with their mother plant was tested using randomly amplified polymorphic DNA (RAPD), inter-simple sequence repeats (ISSR), and start codon targeted (SCoT) molecular markers. The genetic similarity between the micropropagated plantlets and the mother plant of F. palmata was nearly 95.9%, assuring high uniformity and true-to-type regenerated plants. Using micropropagated F. palmata plantlets as a rootstock proved appropriate for the grafting F. carica ‘Brown Turkey’. These findings contribute to the commercial propagation and production of the fig crop.
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Pyts, T. "NAMES OF METAL-PROCESSING CRAFTSMEN IN GERMAN DIALECTS". Вісник Житомирського державного університету імені Івана Франка. Філологічні науки, n. 3(98) (23 dicembre 2022): 171–82. http://dx.doi.org/10.35433/philology.3(98).2022.171-182.
Testo completoAbstract (sommario):
The article studies the Silesian, Low Prussian, and East Pomeranian names of metal-processing craftsmen of the 14th–16th centuries. The article substantiates the topicality of studying the German dialects that disappeared due to the World War II, analyses specialized literature, characterizes the history of studying the German names of craftsmen in the former East-German dialects, determines the level of their coverage, formulates the objective and task of the publication and outlines the perspectives of further academic research. Besides, the article provides the insight into the word-formative peculiarities of the names of craftsmen, the form of their fixation within the Silesian, Low Prussian, and East Pomeranian dialects. Each form is accompanied by the data concerning the time and place of the fixation. The research established, 63 names of metal-processing craftsmen. They include: а) names of manufacturers of small items for household and clerical use; b) makers of arms and armor; c) moulders; d) jewelers and coiners; e) common names to designate smith; f) other names of craftsmen. The formative bases of metal-processing craftsmen were established: а) names of handicrafts; b) names of materials of which they were produced; c) names of craftsmen’s actions; d) names of the color of the processed material; e) according to the general characteristic of the items; f) according to the general characteristic of the materials. Besides, 1/3 of the names of craftsmen are formed with suffixes: -er, -ler, -ner, -ir, -orre, and 2/3 bi-root. The other word-formative bases in the names of the craftsmen with the different roots are as follows: -schmied, -gießer, -macher, -hauer, -feger, -böter, -gräber, -schläger, -schneider, -schlosser, -zieher. 16 synonymic rows can be identified within the established names of metal-processing craftsmen.
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Jones, Shauna Laurel, Edda R. H. Waage e Karl Benediktsson. "Himnesk rödd en helvískur andi? Um friðun álftar á Íslandi og nýlega árekstra álfta og kornbænda". Ritið 19, n. 3 (18 dicembre 2019): 9–43. http://dx.doi.org/10.33112/ritid.19.3.2.
Testo completoAbstract (sommario):
Þegar árekstrar koma upp í sambúð dýra og manna er nauðsynlegt að skoða vel þær forsendur sem að baki liggja. Í greininni er fjallað um þær deilur sem sprottið hafa upp á síðustu árum um alfriðun álftarinnar og tengjast aukinni kornrækt. Í upphafi er gerð stutt grein fyrir nýlegum nálgunum sem tengjast auknum áhuga á sambandi dýra og manna í hugvísindum. Í stað þess að skoða dýr sem óvirka þolendur eða jafnvel vélar, eins og algengt hefur verið um aldir, er nú lögð áhersla á gerendahæfni þeirra og gagnvirk tengsl við umhverfi sitt. Þau eru virkir þátttakendur í lífpólitík hvers tíma. Friðun tegunda er eitt birtingarform slíkrar lífpólitíkur, sem auk líffræðilegrar vitneskju snýst ævinlega um margvísleg gildi og hrif. Friðunarsaga álftarinnar er að því búnu rakin. Ýmsar fornar heimildir og lagaákvæði vitna um mikilvægi hennar sem nytjafugls á fyrstu öldum Íslandsbyggðar. Álftin hafði enn fremur margþætta menningarlega þýðingu í gegnum aldirnar. Þegar fyrsta almenna löggjöf um friðun fugla kom til sögu á nítjándu öld var þó ekki horft sérstaklega til álfta, enda fuglinn enn veiddur að einhverju marki. Nytja- og friðunarsjónarmið tókust á í rökræðum um álftina, sem var loks tekin í hóp alfriðaðra fugla árið 1913. Á síðustu áratugum tuttugustu aldar jókst kornrækt verulega í sveitum landsins. Jafnframt hefur álftum fjölgað og raddir hafa heyrst meðal bænda um að aflétta beri friðun fuglsins. Í rannsókn höfunda á Suðurlandi voru tekin eigindleg ítarviðtöl við níu kornbændur til að varpa skýrara ljósi á sambúð bænda og álfta. Reynsla þeirra og viðhorf voru með ýmsu móti. Flestir töldu álftir vera skynugar skepnur og viðurkenndu gerendahæfni þeirra. Hins vegar töldu þeir almennt ekki að fuglinn hefði sérstakt gildi sökum fegurðar. Flestir töldu að breyta þyrfti ákvæðum um alfriðun álfta. Ábyrgð á þeim árekstrum sem upp hafa komið var oftast varpað á fuglinn. Að rætur árekstranna mætti rekja til athafna þeirra sjálfra var almennt ekki ofarlega í huga bændanna. Í heild sýnir sagan af samskiptum manna og álfta vel hinar flóknu sögulegu rætur og menningarlegu forsendur sem vernd dýrategunda byggir jafnan á. Rannsóknir af þessu tagi, sem nýta kenningar og aðferðir umhverfishugvísinda, eru mikilvægar til að auka skilning á lífpólitík náttúruverndar.
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Loveland, P. "Waldböden: ein Bildatlas der wichtigsten Bodentypen aus Österreich, Deutschland und der Schweiz - edited by Leitgeb, E., Reiter, R., Englisch, M., Lüscher, P., Schad, P. & Feger, K.H." European Journal of Soil Science 64, n. 6 (2 ottobre 2013): 823. http://dx.doi.org/10.1111/ejss.12085.
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Gauer, J. "Book Review: Ernst Leitgeb, Rainer Reiter, Michael Englisch, Peter Lüscher, Peter Schad, Karl-Heinz Feger: Waldböden. Ein Bildatlas der wichtigsten Bodentypen aus Österreich, Deutschland und der Schweiz." Journal of Plant Nutrition and Soil Science 176, n. 4 (23 luglio 2013): 640–41. http://dx.doi.org/10.1002/jpln.201390024.
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Ennis, D. M. "Making Choices without Reference to Chemistry or Brains. Review of New Developments in Psychological Choice Modeling, by Geert De Soete, Hebert Feger, and Karl C. Klauer (Eds.)". Journal of Mathematical Psychology 37, n. 1 (marzo 1993): 136–42. http://dx.doi.org/10.1006/jmps.1993.1008.
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Fimm-Todt, Franziska, Joachim Lauterwasser, Eva-Maria Egenter, Christian Weber, Daniel Feger, Katharina Schaich, Sarah Ulrich et al. "Abstract 4072: Cytotoxic effects of LRRK2 inhibitors in combined treatment with chemotherapeutic agents on a large panel of cancer cell lines". Cancer Research 82, n. 12_Supplement (15 giugno 2022): 4072. http://dx.doi.org/10.1158/1538-7445.am2022-4072.
Testo completoAbstract (sommario):
Abstract Leucin-rich repeat kinase 2 (LRRK2) plays an important role in the onset of sporadic as well as familial Parkinson’s disease. Pathogenic gain-of-function mutations of LRRK2 are associated with aberrant LRRK2 hyperactivity which results in neurotoxicity and protein aggregation caused by dysfunctional autophagy and vesicle trafficking. Thus, the development of LRRK2 inhibitors represents a promising strategy for the treatment of Parkinson’s disease. Interestingly LRRK2 mutations have also been reported to increase the risk for the onset of different types of cancer (e.g. breast, thyroid, lung). Several studies suggest that LRRK2 is involved in the regulation of different cancer-related pathways (e.g. ATM-p53-p21-pathway, JNK pathway). Deregulation of LRRK2 activity caused by mutations has been shown to interfere with these pathways thereby increasing the risk to develop certain types of cancer. Since anti-cancer treatments mostly target the same pathways, we hypothesized that LRRK2 inhibitors may affect anti-cancer treatments in specific cancer cell types. In this study we report on the analyses of various inhibitors (e.g. MLi-2 and PF-06447475) on LRRK2 autophosphorylation at S935 in a cellular phosphorylation assay using the non-small cell lung cancer cell line A549 in comparison to biochemical LRRK2 activity assays. Furthermore, we compare the direct LRRK2 inhibitor effect on the proliferation of 140 cell lines, as well as their potential combinatorial impact on the potency of chemotherapeutic agents (e.g. Adriamycin). The observed effects can help to understand the implications of pharmaceutical LRRK2 inhibition in the treatment of both Parkinson’s disease and cancer. Citation Format: Franziska Fimm-Todt, Joachim Lauterwasser, Eva-Maria Egenter, Christian Weber, Daniel Feger, Katharina Schaich, Sarah Ulrich, Oliver Siedentopf, Frank Totzke, Michael Kubbutat, Jan Erik Ehlert. Cytotoxic effects of LRRK2 inhibitors in combined treatment with chemotherapeutic agents on a large panel of cancer cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4072.
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Schaich, Katharina, Daniel Feger, Oliver Siedentopf, Sarah Ulrich e Jan Erik Ehlert. "Abstract 357: Characterization of KRas pathway inhibitors in 2D and 3D screening formats". Cancer Research 82, n. 12_Supplement (15 giugno 2022): 357. http://dx.doi.org/10.1158/1538-7445.am2022-357.
Testo completoAbstract (sommario):
Abstract The KRas/Raf/MEK signalling axis has been identified to play a critical role in the formation of cancer, resulting in several investigational new drugs targeting this pathway. Identification of appropriate drugs is hampered, however, by the assumption that a three-dimensional setting may be required to observe significant inhibitory effects, possibly due to alternate gene expression and protein activity in such a “closer-to-physiology” setting. In order to explore that topic, in the current study we have made use of our 140 cell lines (CL)-2D proliferation panel (3 days incubation) and our 100CL-3D soft agar panel (> 7 days incubation). On these platforms, we have compared inhibitors targeting the KRas/Raf/MEK pathway via either KRas:SOS interaction (e.g. BI3406), the KRas mutation at G12C (e.g. AMG510), or Raf-kinase (e.g. AZ628) and MEK1/2-kinase activity (e.g. AZD6244). It showed that especially the Raf- and MEK kinase inhibitors exhibited significantly enhanced potency in the 3D soft agar setting in the majority of the cell lines tested. The other inhibitors also showed an increased potency under soft agar conditions, however, on clearly fewer cell lines and usually not as strongly. For all kinds of inhibitors tested, the most significant changes in potency were associated with enhanced efficacy as observed by stronger cell death induction. Differences may be attributable to three-dimensional growth, but also to the elongated duration of the soft agar assay. For selected conditions, we addressed this topic by analyzing the inhibitor impact on 3D spheroid growth after shorter incubation times. Our results show that 3D growth analysis either in the soft agar or spheroid setting clearly supports the development of KRas/Raf/MEK pathway inhibitors. Citation Format: Katharina Schaich, Daniel Feger, Oliver Siedentopf, Sarah Ulrich, Jan Erik Ehlert. Characterization of KRas pathway inhibitors in 2D and 3D screening formats [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 357.
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Cherdron, H. "Polyimide: „Polyimides: Materials, Chemistry and Characterization”︁. Hrsg. von C. Feger, M. M. Khojasteh und J. E. McGrath. Elsevier Science Publishers, Amsterdam 1989. 788 S., Abb., Tab., geb. $ 241.50. ISBN 0-444-88241-3". Nachrichten aus Chemie, Technik und Laboratorium 38, n. 3 (marzo 1990): 362–63. http://dx.doi.org/10.1002/nadc.19900380319.
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Vuaroqueaux, Vincent, Daniel Feger, Anne-Lise Peille, Oliver Siedentopf, Sadhana Panzade, Sarah Ulrich, Sebastian Dempe, Heinz-Herbert Fiebig e Jan Erik Ehlert. "Abstract 1132: A systems biology approach combining ProLiFiler and Cancer Data Miner for an enhanced preclinical characterization of the WEE-1 inhibitor Adavosertib". Cancer Research 82, n. 12_Supplement (15 giugno 2022): 1132. http://dx.doi.org/10.1158/1538-7445.am2022-1132.
Testo completoAbstract (sommario):
Abstract Adavosertib (AZD1775, MK-1775), a clinical stage inhibitor of the tyrosine kinase WEE1, was investigated in a cell proliferation and survival assay with 140 human cancer cell lines (CLs) representing all major tumor types (ProLiFiler platform of Reaction Biology) followed by mechanism of action (MoA) and biomarker analyses using 4HF Biotec’s Cancer Data Miner in silico platform. Adavosertib exhibited a broad anti-cancer activity across all hematological and solid tumor types with IC50 values ranging from 0.06 to 10 µM (median: 0.38 µM), matching the consistently high expression of the WEE1 gene. Among 900 reference compounds, the activity profile of adavosertib correlated best with the profiles of compounds targeting the replication stress response including other WEE1 inhibitors but also inhibitors of checkpoint kinase 1 and 2 (CHK1/2) or ataxia telangiectasia-mutated (ATM). Significant correlations were also seen with compounds blocking mitosis, DNA replication and DNA repair. Interestingly, we observed a subset of cell lines that were resistant to both DNA synthesis and PARP inhibitors but were sensitive to WEE1 inhibition. Moreover, by using multiple datasets of WEE1 inhibitors connected to the molecular annotations of CLs for a data driven biomarker screening, we identified MYC mutations as a predictive marker of sensitivity and PIK3CA or ERBB2 gene amplifications as predictors of resistance. Transcriptome analysis identified up to 900 genes for which higher expression in CLs was associated with CL sensitivity to the compound. Preliminary pathway analysis indicated that these genes are well represented among nuclear factor and Myc-regulated genes. In conclusion, our studies demonstrate broad anticancer activity of adavosertib and confirm its proposed MoA. The biomarkers we identified will facilitate the selection of pre-clinical in vivo tumor models and, if confirmed, even patient selection for clinical trials. The combined use of the ProLiFiler and Cancer Data Miner Platforms has the potential to accelerate and de-risk the development of anti-cancer agents. Citation Format: Vincent Vuaroqueaux, Daniel Feger, Anne-Lise Peille, Oliver Siedentopf, Sadhana Panzade, Sarah Ulrich, Sebastian Dempe, Heinz-Herbert Fiebig, Jan Erik Ehlert. A systems biology approach combining ProLiFiler and Cancer Data Miner for an enhanced preclinical characterization of the WEE-1 inhibitor Adavosertib [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1132.
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Castro, Carla N., Daniel Feger, Sarah Ulrich, Oliver Siedentopf e Jan E. Ehlert. "Abstract 2893: Exploring the combinatorial potential of bispecific T-cell engagers in high throughput format". Cancer Research 82, n. 12_Supplement (15 giugno 2022): 2893. http://dx.doi.org/10.1158/1538-7445.am2022-2893.
Testo completoAbstract (sommario):
Abstract Bispecific antibodies are being explored as a means to modulate responses of the immune system to tumor infiltration. They are emerging as a growing class of immunotherapies with potential to further improve clinical efficacy and safety. Besides tumor-targeted and dual immunomodulators, the most important class of therapeutically relevant bispecific antibodies are engagers of cytotoxic immune cells to kill tumor cells. These are mainly engager of T-cells (BiTE´s), but also NK-cell engager several of which have entered clinics with Blinatumomab (anti-CD3/anti-CD19) being FDA-approved for the treatment of Acute Lymphoblastic Leukemia. Several studies are under way to address potential combinatorial effects with other compounds in clinics. In order to facilitate analysis of the cytotoxic impact of BiTE´s in high throughput, we developed a 384-well format assay system based on Luciferase-labeled tumor cells. This detection technology has many advantages. As only the tumor cells are labeled, the specific detection of luciferase exclusively correlates to the number of viable tumor cells, allowing for co-cultures with high excess of effector cells without them interfering in the detection. Due to high sensitivity, only few tumor cells are required for a decent signal/noise ratio, keeping the overall need for primary effector cells to the lowest, even at high effector/target cell ratios. That can be of great advantage when working with rare cytotoxic subpopulations (e.g. NK-cells), precious samples from patients, or simply saves resources when performing large exploratory studies. In addition, combination of low 384-well format volumes with nanodrop agent dispensing technology minimizes amounts of expensive antibodies and other agents. Applying this technology, we evaluated the combinatorial effects of Blinatumomab with immune modulators (e.g. Lenalidomide), kinase inhibitors (e.g. MEK-inhibitor, Selumetinib) and other clinically relevant agents (e.g. MCL1-inhibitor, S63845) on the Luciferase-labeled GCB-like DLBCL cell line OCI-LY1. Depending on compound combination, we observe synergistic but also antagonistic effects. Our data support the outstanding usefulness of this methodological approach for the exploration of bispecific cytotoxic immune cell engager agents. Citation Format: Carla N. Castro, Daniel Feger, Sarah Ulrich, Oliver Siedentopf, Jan E. Ehlert. Exploring the combinatorial potential of bispecific T-cell engagers in high throughput format [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2893.
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Bernat, James L. "Book Review Intervening in the Brain: Changing Psyche and Society (Ethics of Science and Technology Assessment. Vol. 29.) By Reinhard Merkel, Gerard Boer, and Jörg M. Fegert, with four others. 533 pp. Berlin, Springer, 2007. $99. 978-3-540-46476-1". New England Journal of Medicine 357, n. 20 (15 novembre 2007): 2095–96. http://dx.doi.org/10.1056/nejmbkrev0706190.
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Holtorf, Kaja, Anne-Lise Peille, Daniel Feger, Vincent Vuaroqueaux, Jan Erik Ehlert e Nadine Obier. "Abstract 5157: Development and evaluation of a high-throughput method for rapid detection of surface antigen expression in fixed cells". Cancer Research 84, n. 6_Supplement (22 marzo 2024): 5157. http://dx.doi.org/10.1158/1538-7445.am2024-5157.
Testo completoAbstract (sommario):
Abstract Cell surface proteins are increasingly considered in the development of novel anticancer agents, as demonstrated by recent clinical successes in the field of immuno-oncology and antibody-drug conjugates (ADCs). These conjugates specifically target antigens present on the surface of tumor cells, enabling the delivery of cytotoxic agents to specific tumor sites. During the preclinical development of such compounds, for example, when they are tested on a wide panel of cell lines, it is essential to have a rapid and reliable method for monitoring target expression and distribution. Complementing our 160 Cell line panel ProLiFiler™, we report here the development of a novel method named oncoFLOW-Profiler™ which includes steps of cell fixation, micronic storage, staining, and measurement by flow cytometry. This method is applied in a 96-well format, enabling screening of all cell lines in parallel and analysis of the expression of different targets in just one day. In this proof-of-concept study, we investigated the level of ERBB2 expression across the ProLiFiler panel of 160-cell lines in order to validate this methodology. We first compared the impact of fixation methods and sample storage on knowingly positive and negative control cell lines over a period of several months. ERBB2 measurements from the oncoFLOW-Profiler™ will be analyzed and validated by comparison with various OMICs datasets from the Cancer DataMiner platform (4HF Biotec), including RNA expression, mutational status, and protein expression levels. To determine the expression cutoff of ERBB2 amplified models, results will be analyzed according to gene copy number variation. Finally, the flow cytometry data generated will be investigated for use as a predictor of response to clinically approved ADCs targeting ERBB2: Kadcyla and Enhertu. Here we present a method that we have demonstrated is feasible for investigating cell surface receptor/antigens during preclinical phase of drug development. Our method has enabled us to successfully assess ERBB2 in biological samples and to identify models sensitive to ADCs targeting ERBB2. We will also discuss the results of ongoing experiments analyzing the applicability of this screen to intracellular targets and carbohydrate-based surface antigens, which cannot be analyzed either by transcriptomics or proteomics. Citation Format: Kaja Holtorf, Anne-Lise Peille, Daniel Feger, Vincent Vuaroqueaux, Jan Erik Ehlert, Nadine Obier. Development and evaluation of a high-throughput method for rapid detection of surface antigen expression in fixed cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5157.
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Fimm-Todt, Franziska, Ezgi Dikici, Katharina Schaich, Oliver Siedentopf, Joachim Lauterwasser, Daniel Feger e Jan Erik Ehlert. "Abstract 549: Characterization of the selective inhibitory effect of KRas inhibitors in different cellular assay formats". Cancer Research 83, n. 7_Supplement (4 aprile 2023): 549. http://dx.doi.org/10.1158/1538-7445.am2023-549.
Testo completoAbstract (sommario):
Abstract The proto-oncogene KRas is a well-described small GTPase that functions as a molecular switch for major physiological signaling pathways involved in cell proliferation, differentiation and survival. It has been shown that activating mutations in KRas are among the most common oncogenic drivers of tumorigenesis. Missense mutations of KRas result in constitutive activation due to impaired hydrolysis of GTP which enhances tumor-promoting downstream signaling pathways. Most KRas mutations are located in exon 2 or 3 including the most frequently changed glycine 12 which is present in most pancreatic cancers as well as in colorectal cancers and lung adenocarcinomas. Although direct inhibition of KRas is challenging due to its small size, smooth surface and limited druggable pockets on its surface, first promising drug candidates for selected KRas mutants have been developed in recent years (e.g. Sotorasib, MRTX1133, BI-2852). It was the aim of this study to characterize the selective inhibitory effects of KRas inhibitors in a panel of cancer cell lines harboring different KRas mutations like G12C, G12V or G12D. So, we applied different cellular techniques including phosphorylation assays as well as 2D proliferation and 3D spheroid assays to screen KRas inhibitors for their effect on distinct KRas mutants. Firstly, inhibitors were tested in a cellular assay monitoring phosphorylation of the downstream target ERK at residues Thr202/Tyr204. Analysis applying the cellular pERK AlphaLisa assay showed a high selectivity of several inhibitors for specific KRas mutants, while RAF and MEK inhibitors showed no significant selectivity in the panel of cancer cell lines tested here. Next, KRas inhibitors were tested in a cellular 2D proliferation and a 3D spheroid assay to determine the inhibitory effect on cell growth in both settings. In line with published data, for some inhibitors we could observe a high selectivity for a specific KRas mutant which was even more pronounced in the 3D format as compared to the 2D setup. Most likely due to the fact that 3D growth assays mimic physiological conditions more closely than 2D settings. Interestingly, in the 2D and 3D assays we could not find such a clear inhibitory effect of the MEK and RAF inhibitors as compared to the cellular pERK assay. These results indicate that the described cellular pERK AlphaLisa assay established for selected cancer cell lines could be a useful tool to screen newly developed KRas inhibitors for their selective inhibition of specific KRas mutants. Additionally, the application of not only 2D proliferation but also 3D growth studies can further characterize the inhibitory potential of these KRas inhibitors. Citation Format: Franziska Fimm-Todt, Ezgi Dikici, Katharina Schaich, Oliver Siedentopf, Joachim Lauterwasser, Daniel Feger, Jan Erik Ehlert. Characterization of the selective inhibitory effect of KRas inhibitors in different cellular assay formats [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 549.
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Castro, Carla, Philipp Metzger, Daniel Feger, Sarah Ulrich, Oliver Siedentopf, Jan E. Ehlert e Holger Weber. "Abstract 4419: Use of luciferase-labeled target cells to explore immune cell killing in high throughput format in 2D and 3D co-cultures". Cancer Research 83, n. 7_Supplement (4 aprile 2023): 4419. http://dx.doi.org/10.1158/1538-7445.am2023-4419.
Testo completoAbstract (sommario):
Abstract With the development and approval of cutting-edge immune-based approaches for cancer treatment in recent years, the global immune-oncological (IO) pipelines have dramatically increased. To overcome the challenges of rising treatment resistance, new strategies are being developed pointing towards enhancing and sustaining T cell-mediated cytotoxicity, exploiting NK, monocytes and γδT cell killing capacity, and combinatorial therapies, among others. Examples of such strategies are the bispecific antibodies, which are mainly T-cell (BiTE) engagers, but also NK-cell engagers. In addition to the FDA approved immune checkpoint inhibitors, monoclonal antibodies against tumor antigens are being developed to enhance the cytotoxic response of NK and macrophages/monocytes through antibody-induced cell cytotoxicity (ADCC) To facilitate the efficacy analysis of BiTEs, we developed a 384-well format assay system based on luciferase-labeled tumor cells (advantages: high-throughput capability, non-radioactive, non-toxic, relatively low cost, and easily adaptable to automation). As only the tumor cells are labeled, the specific detection of luciferase exclusively correlates to the number of viable tumor cells, allowing for co-cultures with high excess of effector cells without the effector cells causing interference. Due to high sensitivity, few tumor cells are required for a sufficient signal/noise ratio, keeping the overall need for primary effector cells to a minimum, even at high effector/target cell ratios. This is of great advantage when working with rare cytotoxic subpopulations (e.g. NK cells), precious samples from patients, or simply saves resources when performing large exploratory studies. In addition, combination of low 384-well format volumes with nanodrop agent dispensing technology minimizes the amounts of expensive antibodies and other agents. Applying this technology, we evaluated the combinatorial effects of Blinatumomab with other clinically relevant agents on the luciferase-labeled GCB-like DLBCL cell line OCI-LY1. Depending on compound combination, we observe synergistic (e.g. Lenalidomide) but also antagonistic effects (e.g. MEK-inhibitor, Selumetinib, and MCL-1-inhibitor, S63845). We also developed CD3-stimulated T cell killer assays either using target cells grown in monolayer or spheroids, with the intent to study checkpoint inhibitors or other T cell activation modulators. In contrast to target cells grown in monolayers, immune cytotoxicity of spheroids by anti-CD3 stimulated T cells was incomplete, showing the additional challenge for effector cells when using 3D cultures as targets. Moreover, we show an ADCC example using NK as cytotoxic cells. Our data supports the outstanding usefulness of this methodological approach for the exploration of the overall efficiency of a therapy to enhance tumor cell killing by immune effector cells. Citation Format: Carla Castro, Philipp Metzger, Daniel Feger, Sarah Ulrich, Oliver Siedentopf, Jan E. Ehlert, Holger Weber. Use of luciferase-labeled target cells to explore immune cell killing in high throughput format in 2D and 3D co-cultures. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4419.
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Wright, W. W. "Advances in polyimide science and technology, proceedings of the fourth international conference on polyimides. Edited by C. Feger, M. M. Khojasteh and M. S. Htoo. Technomic Publishing Co. Inc., Pennsylvania, USA, 1993. pp. xi + 706, price SWfr238. ISBN 0-87762-983-8". Polymer International 33, n. 3 (marzo 1994): 342. http://dx.doi.org/10.1002/pi.1994.210330320.
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40
Vuaroqueaux, Vincent, Nadine Obier, Anne-Lise Peille, Daniel Feger, Katharina Schaich, Thomas Metz, Sebastian Dempe, Heinz-Herbert Fiebig e Jan Erik Ehlert. "Abstract 4895: Introduction of a platform for preclinical profiling of drug conjugates: a case study with sacituzumab govitecan". Cancer Research 83, n. 7_Supplement (4 aprile 2023): 4895. http://dx.doi.org/10.1158/1538-7445.am2023-4895.
Testo completoAbstract (sommario):
Abstract Drug-conjugates are an emerging class of anticancer agents combining the cytotoxic activity of highly potent chemotherapeutic agents with the target specificity of an antibody, a small molecule or a peptide ligand directed against a cancer-associated protein. With nearly half a century of development, profound advancements have been made in the development of these therapeutics. The most advanced are antibody-drug conjugates (ADCs) with currently >100 in development and 11 approved by the FDA. To facilitate preclinical evaluation of novel drug conjugates, Reaction Biology and 4HF Biotec have developed a dedicated platform allowing specific in vitro and in silico analyses for this class of therapeutics. The platform is intended to provide information on the potency of the drug conjugate over the corresponding stand-alone cytotoxin, the cancer entities to be treated, the target engagement and the determinant(s) of cancer cell sensitivity. Here, we present our platform to refine antitumor potential of Sacituzumab govitecan (ScG), a recently approved TROP-2 targeted ADC used for the treatment of triple-negative breast cancer. First, we used the ProLiFiler™ (Reaction Biology), a cell proliferation and survival assay with 140 human cancer cell lines, to establish the antitumor profile of ScG, its payload SN-38 and three other cytotoxins (camptothecin, MMAE and mertansine) to validate the results of our assay. The IC50 obtained for the cytotoxins were next validated using the MoAFinder (4HF Biotec), a tool derived from the NIH COMPARE algorithm that ranks drugs based on the similarity of their growth inhibitory profiles. The analysis confirmed that SN-38 and camptothecin antitumor profiles, as established with the ProLiFiler, correlated best with other topoisomerase-1 inhibitors from our database of more than 1,000 compounds. Mertansine and MMAE correlated best with tubulin inhibitors and were more potent than camptothecin and SN-38. Overall, the response to these cytotoxins was stronger in cell lines from hyperproliferative cancers such as hematological malignancies than in those from solid cancers. Next, by using OMICS data (internal and publicly available), qPCR and flow cytometry connected to drug sensitivity profiles, we will present a differential biomarker screen of ScG vs. SN-38 to identify molecular determinants of sensitivity toward the ADC and its cytotoxin. We will address the expression level of TROP2 and its predictivity for tumor cell sensitivity, screen for predictors of SN-38 response and investigate possible off-target effects in cell lines sensitive to ScG but lacking TROP2 expression. Overall, the study demonstrates the potential of our platform to investigate drug conjugates. The comparative profiling of ScG and its payload allows to identify candidate cancer entities for ScG treatment and to improve patient enrollment into clinical trials using biomarkers. Citation Format: Vincent Vuaroqueaux, Nadine Obier, Anne-Lise Peille, Daniel Feger, Katharina Schaich, Thomas Metz, Sebastian Dempe, Heinz-Herbert Fiebig, Jan Erik Ehlert. Introduction of a platform for preclinical profiling of drug conjugates: a case study with sacituzumab govitecan. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4895.
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Peille, Anne-Lise, Kaja Holtorf, Pablo Anton Garcia, Nadine Obier, Daniel Feger, Thomas Metz, Sebastian Dempe, Heinz-Herbert Fiebig, Jan Ehlert e Vincent Vuaroqueaux. "Abstract 4708: Potency and selectivity of ERBB2-targeting antibody drug conjugates in vitro". Cancer Research 84, n. 6_Supplement (22 marzo 2024): 4708. http://dx.doi.org/10.1158/1538-7445.am2024-4708.
Testo completoAbstract (sommario):
Abstract Previously we have reported on the relevance of the joint ProLiFiler and Cancer DataMiner platforms when studying the antitumor efficacy of novel antibody-drug conjugates (ADCs), such as Sacituzumab govitecan. In this study, we use our platforms to investigate and compare the selectivity of two FDA-approved Trastuzumab-based ADCs targeting ERBB2: Kadcyla, the first-in-class ADC employing a microtubule inhibitor bound via a non-cleavable linker, and Enhertu, which combines a topoisomerase inhibitor with a protease-cleavable linker. We performed a cell proliferation and survival assay using the ProLiFilerTM (Reaction Biology) to characterize the in vitro antitumor effects of Enhertu, Kadcyla, and their individual cytotoxins, deruxtecan & mertansine on 160 human cancer cell lines (CLs). The resulting data were uploaded to 4HF´s Cancer DataMiner platform for data analysis. First, we confirmed high potency and limited selectivity of mertansine, as it displayed an IC50 < 250 nM (mean: 27.3 nM) in 95% of cell lines (CLs). A COMPARE analysis confirmed that mertansine data correlated best with those of other microtubule inhibitors in our drug databases (e.g., MMAE, Spearman rho = 0.79, p=9.6E-27). Conversely, a paired analysis showed that CLs were less sensitive to Kadcyla than to mertansine except for CLs overexpressing ERBB2. The 160-CL panel included a total of nine CLs (six mammary, two gastric, one ovarian) with strong ERBB2 overexpression (Affymetrix data >10), mostly associated with ERBB2 gene amplification; seven of them were the most sensitive CLs to Kadcyla (IC50 < 6 nM). Focusing solely on breast cancer cell lines (breast cancer is the approved indication for Kadcyla), we observed a strong correlation between sensitivity to Kadcyla and ERBB2 expression (Spearman r = -0.78, p = 0.003). Interestingly, in line with published data, the ERBB2-overexpressing cell lines SNU-216 (stomach cancer) and JIM-T1 (breast cancer) were less sensitive to Kadcyla. In non-ERBB2-amplified CLs, Kadcyla sensitivity did not correlate with ERBB2 expression levels. Focusing on ERBB2-negative CLs such as hematological CLs, we unexpectedly observed consistent cell inhibition (mean IC50 =33 nM) with Kadcyla, suggesting that the ADC was cleaved, and the payload released into the medium. Overall, this study has demonstrated the relevance of our platforms to study and compare newly developed ADCs. Cytotoxic activities recorded for conjugates and free payloads, along with molecular data for the test cell lines, provides insight in the mode of action of conjugates and their target cell populations and hence can support the development of ADCs. Investigations are underway with Enhertu and its payload deruxtecan, and results will be compared with those obtained for Kadcyla and mertansine. Citation Format: Anne-Lise Peille, Kaja Holtorf, Pablo Anton Garcia, Nadine Obier, Daniel Feger, Thomas Metz, Sebastian Dempe, Heinz-Herbert Fiebig, Jan Ehlert, Vincent Vuaroqueaux. Potency and selectivity of ERBB2-targeting antibody drug conjugates in vitro [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4708.
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Krueger, W., D. Feger, A. Friedman, T. Doan e K. D’silva. "POS1498 COMORBIDITIES AND SAFETY EVENTS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS". Annals of the Rheumatic Diseases 82, Suppl 1 (30 maggio 2023): 1106.1–1106. http://dx.doi.org/10.1136/annrheumdis-2023-eular.2379.
Testo completoAbstract (sommario):
BackgroundSystemic lupus erythematosus (SLE) is a complex autoimmune disease with multiorgan involvement. High disease activity may drive the development of comorbidities and safety events in SLE.ObjectivesTo assess the prevalence of comorbidities and history of safety events at the time of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) assessment and the incidence of newly diagnosed comorbidities and safety events post-SLEDAI assessment among a prevalent cohort of adult SLE patients ≥18 years old.MethodsThis was a retrospective observational cohort study using the OM1 SLE Registry data from January 2013 to February 2022 (OM1, Inc., Boston, MA). The index date was defined as the first observed or estimated SLEDAI score with ≥12 months of prior data occurring after the first observed SLE diagnosis. The baseline period included all observed time prior to and including the index date. The follow-up period for identifying incident comorbidities and safety events included all available data after the index date. Incidence rates were stratified by disease activity.ResultsAmong 10,837 patients, mean age was 52 years and 92% were female. The most common existing comorbidities were hypertension (44%), fibromyalgia (32%), anemia (29%), dyslipidemia (29%), thyroid disease (26%), obesity (25%), depression (22%), rheumatoid arthritis (22%), anxiety (19%), and Sjögren’s syndrome (18%). History of safety events at baseline most commonly included any infection (11%), abnormal liver function tests, hepatitis, or acute liver injury (ALI) (8%), elevated creatinine or acute kidney injury (AKI) (6%), and any malignancy (5%). Most patients were treated with first-line therapy for SLE (glucocorticoids and/or antimalarials) during follow-up (89%). Use of second-line (methotrexate, azathioprine, leflunomide) and third-line (belimumab, anifrolumab, mycophenolate mofetil, mycophenolic acid, tacrolimus, cyclosporine, voclosporin, rituximab) SLE therapies were less common (29% and 30%, respectively). During follow-up, 36% of patients had no disease activity, 28% had mild activity, 22% had moderate activity, and 14% had severe activity. Greater disease activity was associated with higher rates of incident hypertension, dyslipidemia, anxiety, thyroid disease, end-stage renal disease or dialysis, chronic liver disease/cirrhosis, avascular necrosis, seizures or epilepsy, and Sjögren’s syndrome. The most common incident safety events regardless of disease activity were any infection (30.7 per 1000 person-years [PY]), abnormal liver function tests, hepatitis, or ALI (20.3 per 1000 PY), and elevated creatinine or AKI (17.9 per 1000 PY). Correlation between incident safety events and disease activity varied by outcome.ConclusionMany common comorbidities occur more frequently among patients with higher SLE disease activity. The association between disease activity and the incidence of safety events was less clear. SLE-related systemic inflammation, comorbidities, and effects of SLE treatment (both positive and negative) likely contribute to patients’ risk profiles.Table 1.Incidence Rates per 1000 person-years Stratified by Index SLEDAI ScoreComorbidity or Safety EventNo Activity N=3,919Mild N=3,022Moderate N=2,413Severe N=1,483Hypertension38.038.742.743.3Dyslipidemia31.832.034.335.7Anxiety26.930.932.338.5Thyroid disease23.624.327.229.0End-stage renal disease or dialysis3.23.63.65.3Chronic liver disease3.64.05.05.2Avascular necrosis2.52.93.44.4Seizures or epilepsy5.36.37.18.4Sjögren’s syndrome7.27.88.212.7Abnormal liver function16.322.425.419.2Abnormal kidney function14.420.920.318.0Any infection24.72336.430.6Major adverse cardiovascular events8.19.26.36.6Venous thromboembolism2.34.44.04.6Any malignancy7.04.65.65.2Disease activity cutoffs: No activity (SLEDAI=0), low (SLEDAI=1-5), moderate (SLEDAI=6-10), severe (SLEDAI=11+)AcknowledgementsThe authors would like to thank OM1, Inc. for providing the data and statistical analysis for this project. Financial support for the study was provided by AbbVie. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship.Disclosure of InterestsWhitney Krueger Shareholder of: AbbVie, Employee of: AbbVie, Danielle Feger Shareholder of: AbbVie, Employee of: AbbVie, Alan Friedman Shareholder of: AbbVie, Employee of: AbbVie, Thao Doan Shareholder of: AbbVie, Employee of: AbbVie, Kristin D’Silva Shareholder of: AbbVie, Employee of: AbbVie.
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Kleinert, S., P. Rapp, F. Schuch, M. Ronneberger, J. Wendler, P. Sternad, F. Popp et al. "AB0494 COGNITIVE IMPAIRMENT IN AXIAL SPONDYLOARTHRITIS?" Annals of the Rheumatic Diseases 80, Suppl 1 (19 maggio 2021): 1274–75. http://dx.doi.org/10.1136/annrheumdis-2021-eular.1353.
Testo completoAbstract (sommario):
Background:There is some evidence that neuropsychiatric changes occur in systemic lupus(1) and rheumatoid arthritis(2). However, little is known regarding a possible disease-related impairment of cognitive abilities in axial spondyloarthritis (axSpA).Objectives:To evaluate patients with axSpA regarding cognitive impairments.Methods:Patients with axSpA attending two rheumatology practices were routinely evaluated by rheumatologists and underwent a computer-based memory and attention test (MAT) (3, 4) with subscale scores ranging from 0 (worst) to 15 (best). The results of short-term memory and working memory were compared to an age-, sex- and education-matched control group of healthy subjects. Descriptive results are presented as median (IQR) for interval data and n (%) for nominal data if not stated otherwise. Two-tailed Wilcoxon signed-rank tests including Bonferroni-Holm adjustment for multiple tests were conducted to investigate the magnitude of potential differences in cognitive abilities.Results:101 consecutive patients were tested (Table 1). After multiple testing adjustment for two subscales, Wilcoxon signed-rank tests returned significant findings for working memory (V = 539.5, p = 0.006, |r| = 0.204) but not for short-term memory (V = 1075, p = 0.351, |r| = 0.078). Regarding the scales’ anchors, descriptive results on pairwise differences suggested axSpA patients to have working memory scores that are on average 10.7% lower compared to control participants (mean Δ= -1.64, SD Δ= 5.95).Table 1.Patients and disease characteristicsn%MeanSDMedian25% Quantile75% QuantileAge10110051.111.6524260Age (female)4847.552.611.75444.561Age (male)5352.549.811.5514157< 13 years formal education4746.5≥ 13 years formal education5453.5HLA B27 positive n/N64/9263.4Disease duration (years)10110013.711.712421Disease duration (female, years)4847.511.69.99417.2Disease duration (male, years)5352.515.512.915523BASDAI9291.13.71.73.82.45BASFI9190.132.42.31.24.5BASMI7574.31.92.3103ASDAS98972.30.82.31.82.8Conclusion:The MAT computerized testing is a feasible test and was well accepted by patients. Results regarding working memory suggest that cognitive abilities needed to accomplish everyday tasks may be impaired in axSpA patients. Further work is needed to characterise possible causes of or associations with this cognitive impairment.References:[1]Zabala A, Salgueiro M, Saez-Atxukarro O, Ballesteros J, Ruiz-Irastorza G, Segarra R. Cognitive Impairment in Patients With Neuropsychiatric and Non-neuropsychiatric Systemic Lupus Erythematosus: A Systematic Review and Meta-analysis. J Int Neuropsychol Soc. 2018:1-11.[2]Vitturi BK, Nascimento BAC, Alves BR, de Campos FSC, Torigoe DY. Cognitive impairment in patients with rheumatoid arthritis. J Clin Neurosci. 2019;69:81-7.[3]Adler G, Bektas M, Feger M, Lembach Y. [Computer-based assessment of memory and attention: evaluation of the memory and attention test (MAT)]. Psychiatr Prax. 2012;39(2):79-83.[4]Adler G, Lembach Y. Memory and selective attention in multiple sclerosis: cross-sectional computer-based assessment in a large outpatient sample. Eur Arch Psychiatry Clin Neurosci. 2015;265(5):439-43.Acknowledgements:This study was funded by the RHADAR GbR (A Network of Rheumatologists), Bahnhofstr. 32, 82152 Planegg, Germany. RHADAR GbR has received a grant for this study from Novartis Pharma GmbH.Disclosure of Interests:Stefan Kleinert Consultant of: Novartis, Abbvie, Grant/research support from: Novartis, Praxedis Rapp: None declared., Florian Schuch Speakers bureau: Novartis, Abbvie, Gilead, Consultant of: Novartis, Abbvie, Gilead, Monika Ronneberger: None declared., Joerg Wendler Speakers bureau: Roche, Pharma, JanssenCilag, Novartis, Abbvie, Consultant of: JanssenCilag, Patrizia Sternad: None declared., Florian Popp: None declared., Peter Bartz-Bazzanella: None declared., Cay-Benedict von der Decken: None declared., Kirsten Karberg Speakers bureau: Roche, Sanofi, Abbvie, Lilly, Georg Gauler Speakers bureau: Abbvie, Gilead, Novartis, Lilly, Consultant of: Lilly, Gilead, Abbvie, Patrick Wurth Speakers bureau: Abbvie, Lilly, UCB, Medac, Susanna Spaethling-Mestekemper Speakers bureau: Abbvie, BMS, Celgene, Gilead, GSK, Hexal, Lilly, MSD, Novartis, Pfizer, Sanofi, UCB, Christoph Kuhn: None declared., Matthias Englbrecht Speakers bureau: AbbVie, Chugai, Eli Lilly, Novartis, Roche, Sanofi, Mundipharma, Paid instructor for: AbbVie, Chugai, Roche, Consultant of: AbbVie, Novartis, Roche, Sanofi, Grant/research support from: Roche, Chugai, Wolfgang Vorbrüggen: None declared., Georg Adler: None declared., Martin Welcker Speakers bureau: Abbvie, Actelion, Amgen, Biogen,BMS, Berlin Chemie, Celgene, Galapagos, Gilead, GSK, Hexal, Janssen, Medac, MSD, Mundipharma, Mylan, Novartis, Pfizer, Roche, Sanofi, SOBI, UCB, Grant/research support from: Novartis, Abbvie.
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Lynce, Filipa, Candace Mainor, Xue Geng, Greg Jones, Ilana Schlam, Hongkun Wang, Ute Feger et al. "Abstract PD9-02: Peripheral immune subsets and circulating tumor DNA (ctDNA) in patients (pts) with residual triple negative breast cancer (TNBC) treated with adjuvant immunotherapy and/or chemotherapy (chemo): The OXEL study". Cancer Research 82, n. 4_Supplement (15 febbraio 2022): PD9–02—PD9–02. http://dx.doi.org/10.1158/1538-7445.sabcs21-pd9-02.
Testo completoAbstract (sommario):
Abstract Background: Poor clinical outcomes are noted in pts with TNBC who do not achieve a pathologic complete response (pCR). We characterized peripheral immune subsets and the role of minimal residual disease (MRD) detection via ctDNA in pts who participated in the OXEL study. Methods: OXEL (Opdivo® -XELoda ®) is a recently completed phase II open-label 3-arm randomized study of nivolumab (nivo), capecitabine (cape) or the combination as adjuvant therapy (tx) for pts with residual TNBC after appropriate neoadjuvant chemo. Residual disease was defined as ≥ 1.0 cm of primary tumor and/or nodal involvement. Eligible pts had completed definitive local tx. Pts were randomly assigned to nivo 360 mg iv q3wks x 6 (arm A); cape 1250mg/m2 po bid D1-D14 q3 wks x 6 (arm B); nivo 360mg iv q3wks + cape 1250mg/m2 po bid D1-D14 q3 wks x 6 (arm C). Peripheral blood mononuclear cells (PBMCs) and ctDNA were assessed at baseline (D1 of cycle 1), 6, and 12 wks and at time of recurrence, if applicable. PBMCs were stained with 30 markers and analyzed by flow cytometry to identify changes in 158 immune cell subsets at 6 wks, as a percent of total PBMCs. RaDaRTM, a deep sequencing based, tumor-informed personalized assay was utilized to detect the presence of ctDNA in plasma. Distant disease-free survival (DDFS) and overall survival (OS) were analyzed by the Kaplan-Meier method and Log-Rank test was used to compare DDFS and OS according to baseline MRD results. All pts will be followed for distant recurrence and survival for 3 yrs. Here we report the translational endpoints of the OXEL study. Clinical endpoints according to treatment received will be reported in a future analysis. Results: 45 pts were enrolled between 8/2018 and 6/2021. 29 (64%) were Caucasian and 14 (31%) were African American. Mean age at enrollment was 51 [+/- 12]. 93% of pts received a taxane-anthracycline containing neoadjuvant tx. 15 pts were randomized to each arm. DDFS probability at 1-yr and 2-yrs was 0.71 (+/- 0.07) and 0.66 (+/- 0.08) respectively. At 12 mos of median follow up, 13/45 pts (29%) experienced distant recurrence, none had local recurrence. 43 pts were evaluated for PBMC subsets. Changes in PBMC subsets at 6 wks were different amongst the arms; in arm A, reductions in NK subsets, including a 33% reduction in CD56dimCD16- cells, were observed, while in arm B, increases in naïve CD4+ T cells (+45%) and CD73+CD8+ T cells (+12%) and reductions in ki67+CD8+ T cells (-48%) were noted. In arm C, increases were observed in conventional dendritic cells (+36%), effector memory ki67+CD4+ T cells (+46%), and CD56dimCD16- NK cells (+29%). 33 pts underwent successful MRD analysis. 12/33 (36%) pts were MRD+ at baseline. 2/12 pts MRD+ at baseline subsequently cleared MRD, with undetectable ctDNA on future time points; neither patient has had recurrence to date. The remaining 10/12 MRD+ pts (83%) have experienced distance recurrence. 21/33 (64%) pts were ctDNA negative at baseline; 20/33 remained negative for all follow up timepoints. 10/11 pts experiencing distant recurrence were MRD+ at baseline, compared to 1/11 pt who became MRD+ at wk 6 post initiation of tx. At 12 mos of median follow-up, baseline MRD+ testing was significantly associated with an inferior DDFS ( p<0.0001 Log-rank test, median DDFS 4.0 mos vs. not reached) and OS (p=0.02 Log-rank test, median OS not reached for both groups). Results will be updated at the time of abstract presentation. Conclusions: Changes in PBMC subsets were associated with receipt of chemo and/or immunotherapy. Our results suggest that baseline MRD+ in pts without pCR is a poor prognostic factor. Future trials aiming to optimize adjuvant treatment with chemo and/or immunotherapy in residual TNBC should consider incorporating ctDNA as a selection marker of pts at higher risk of recurrence. Citation Format: Filipa Lynce, Candace Mainor, Xue Geng, Greg Jones, Ilana Schlam, Hongkun Wang, Ute Feger, Renee Donahue, Nicole Toney, Caroline Jochems, Jeffrey Schlom, Christopher Gallagher, Rita Nanda, Deena Graham, Erica M Stringer-Reasor, Neelima Denduluri, Julie Collins, Asma A Dilawari, Ami Chitalia, Shruti Tiwari, Raquel Nunes, Rebecca Kaltman, Katia Khoury, Margaret Gatti-Mays, Sandra M Swain, Heather A. Parsons, Paula Pohlmann, Claudine Isaacs. Peripheral immune subsets and circulating tumor DNA (ctDNA) in patients (pts) with residual triple negative breast cancer (TNBC) treated with adjuvant immunotherapy and/or chemotherapy (chemo): The OXEL study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD9-02.
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Pintos Amengual, Gabriel. "Ciencia y náutica. Los textos de pilotaje del siglo XVIII". Vínculos de Historia Revista del Departamento de Historia de la Universidad de Castilla-La Mancha, n. 12 (28 giugno 2023): 343–57. http://dx.doi.org/10.18239/vdh_2023.12.18.
Testo completoAbstract (sommario):
RESUMENEn este artículo se trata de analizar los textos de pilotaje utilizados en el siglo xviii y su adecuación a la ciencia del momento. Para ello, abordamos el estado de la ciencia mediante el establecimiento de los hitos que marcaron la evolución de la navegación astronómica científica y, por otra parte, realizamos el análisis comparativo de los textos, para finalmente determinar si estos adoptaron o no los adelantos de la ciencia náutica y en su caso el periodo transcurrido hasta incluirlos en los textos. Palabras clave: ciencia, náutica, astronomía de posición, textos náuticos Topónimos: EspañaPeriodo: siglo xviii ABSTRACTThis article tries to analyze the pilotage texts used in the 18th century and their adaptation to the existing science. To do this, we address the state of science by establishing the milestones that marked the evolution of scientific astronomical navigation; on the other hand, we perform a comparative analysis of the texts. We finally determine whether or not they adopted the advances in nautical science and where appropriate, the period that elapsed until such advances were included in the texts. Keywords: science, nautical science, position astronomy, nautical textsPlace names: SpainPeriod: 18th century REFERENCIASAlberola Romá, A. y Die Maculet, R. (2013): Jorge Juan y Santacilia: ciencia, educación y enseñanza en la España del siglo xviii. Jorge Juan y la ciencia ilustrada en España (pp. 63-82), Madrid, Ministerio de Defensa.Alfonsini, L. (2011): Étienne Bézout (1730-1783), Mathématicien del lumières. Paris, L´Harmattan.Archer, M. (1756): Lecciones náuticas, explicadas en el Museo Matemático del M.N. y M.L. Señorío de Vizcaya, Noble Villa de Bilbao, Bilbao: Antonio de Eguzquisa Impresor de dicho M.N. y M.L. Señorío.Arroyo Ruiz-Zorrilla, R. (1989): Apunte para una historia de la enseñanza de la náutica en España, Madrid, Centro de Publicaciones del Ministerio de Transportes Turismo y Comunicaciones.Barreda, F. de (1765): El marinero instruido en el arte de navegación especulativo, y práctico, según el método, con que se enseña a los colegiales del Real Seminario de Sr. San Telmo, extramuros de la Ciudad de Sevilla, Sevilla. Bezout, E. (1781): Cours de mathématiques. A l’usage des gardes du Pavillon et de la Marine. Contenant le Traité de Navigation, De L’Imprimerie De PH.- D. Pierres. Paris.Bourne, W. (1574): A Regiment for the Sea: Conteyning most profitable Rules, Mathematical experiences, and perfect knowledge of Navigation, for all Coastes and Countreys: most needefull and necessarie for all Seafaring men and Travellers, as Pilotes, Mariners, Marchants, c. London, H. Bynneman for Thomas Hacket.Cedillo y Rujaque, P. M. (1717): Compendio de la arte de navegar, Sevilla, Lucas Martín de Hermosilla. — (1745): Tratado de de cosmografía y náutica, Cádiz: En la imprenta Real de Marina, y Casa de la Contratación de don Miguel Gómez Guiráun.Cotter, C. H. (1968): A history of nautical astronomy, London-Sydney-Toronto, Hollis y Carter.Fernández de Navarrete, M. (1846): Disertación sobre la historia de la náutica y de las ciencias matemáticas. Que han contribuido á sus progresos entre los españoles, Madrid, Imprenta de la viuda de Calero.García Franco, S. (1947): Historia del arte y ciencia de navegar. Desenvolvimiento histórico de los cuatro términos de la navegación, 2 volúmenes, Madrid, Instituto histórico de Marina.García Garralón, M. (2007): Taller de mareantes: El Real Colegio Seminario de San Telmo de Sevilla (1681-1847), 2 volúmenes, Sevilla, Cajasol Obra Social.García Sevillano, J. (1736): Nuevo régimen de navegación, Madrid, Joaquín Sánchez.Gaztañeta Yturribalga, A. (1692): Norte de la navegación hallado por el cuadrante de reducción, Sevilla: por Juan Francisco de Blas impresor mayor de dicha ciudad.— (1693): Cuadrante geométrico universal para la conversión esférica a lo plano, aplicado al arte de navegar.González González, F. J. (1992): Astronomía y navegación en España siglos XVI-XVIII, Madrid: Mapfre.— (2006): Del arte de marear a la navegación astronómica: Técnicas e instrumentos de navegación en la España de la Edad Moderna, Cuadernos de Historia Moderna, 135-166. Guillén Tato, J. F. (1935): La náutica española en el siglo xvii, Madrid, Gráfica Universal.Hewson, J.B. (1983): A history of the practice of navigation. Glasgow. Browm, Son Ferguson, Limited.Hormigón, M. (1995): Paradigmas y matemáticas: Un modelo teórico para la investigación en historia de las matemáticas, Zaragoza. Ibáñez Fernández, M. D. (2000): La difusión de conocimientos náuticos en la España decimonónica: La navegación astronómica en los textos de náutica españoles del siglo xix. Tesis doctoral. Bilbao: Universidad del País Vasco.— (2002): Tratados españoles de náutica (siglos xvi-xvii). Historia Naval. Instituto de Historia Naval, 20 (76), 35-57.— (2011): Evolución de la navegación astronómica en el siglo xix, Eusko Ikaskuntza, 209-242.Ibáñez Fernández, y Llombart, J. (2001): La comparación de textos en historia de la ciencia: Una propuesta metodológica. Llull. Revista de la Sociedad Española de Historia de las Ciencias y de las Técnicas, 24 (49), 131-148. Iglesia Martín, M.A. (2000): Estudio comparativo desde el punto de vista matemático de textos náuticos españoles del siglo xviii. Tesis doctoral. Leioa, Servicio Editorial de la Universidad del País Vasco.Juan y Santacilia, J. (1757): Compendio de Navegación para el uso de los caballeros guardias-marinas, Cádiz, En la Academia de los mismos Caballeros.Juan y Santacilia y Ulloa, A. (1748): Observaciones astronómicas y phísicas hechas en los Reynos del Perú, Reynos del Perú, por D. Jorge Juan, Comendador de Aliaga en el Orden de S. Juan, Socio Correfpondiente de la R. Academia de las Ciencias de París, y D.Antonio Ulloa, de la R. Sociedad de Londres, ambos Capitanes de Fragata de la R. Armada de las cuales se deduce la figura y magnitud de la tierra y se aplica a la Navegación. Madrid, Por Juan de Zuñiga.Koyré, A. (1990): Estudios galineanos, Quinta edición, Madrid, Siglo veintiuno de España Editores, S.A.Laguarda Trías, R. A. (1959): Comentarios sobre los orígenes de la navegación astronómica, Madrid, Consejo Superior de Investigaciones Científicas. Instituto Histórico de Marina.León Mantero, C., Santiago, A., Gutiérrez, M.P. (2020): “El método de máximos y mínimos en los libros de texto españoles”, En las matemáticas en España durante el siglo xviii a través de los libros y sus autores, Salamanca, Editorial Universidad, pp. 115-133.Llombart Palet, J, y Hormigón Blázquez, M. (1990): Un libro de texto de la escuela de náutica y matemáticas de Bilbao en el siglo xviii, en R. Codina y R. Llobera Jiménez, (Coords.), Historia, ciencia i ensenyament: Actes del III Simpòsium d’Enssenyament i Història de les Ciències i de les Tècniques, Barcelona, 1988, 439-452.Llombart Palet, J., y Iglesias Martín, M. A. (1998): Las aportaciones vascas al “arte de navegar” en algunos libros de náutica, Itsas memoria: revista de estudios marítimos del País Vasco, (2), 525-536.López Piñero, J. M. (1979): Ciencia y técnica en la sociedad española de los siglos xvi y xvii, Barcelona, Labor, S.A.Louzán Lago, F. (2005): Génesis y evolución de los instrumentos de alturas usados en navegación: Análisis de los errores cometidos durante las observaciones. Tesis doctoral. A Coruña, Universidade da Coruña.Manterola Zabala, M. (2016): Las matemáticas en los estudios de náutica en España en el siglo xviii: Estudio comparativo de los libros de texto empleados en la formación de pilotos y guardiamarinas. Tesis doctoral. Universidad de la Rioja: Programa de Doctorado de Ingeniería Eléctrica, Matemáticas y Computación. Departamento de matemáticas y Computación.Martínez Ruiz, E. (2013): La España Ilustrada de Jorge Juan. Jorge Juan y la ciencia ilustrada en España. Instituto de Historia y Cultura Naval XLVII Jornadas de Historia Marítima. Ciclo de Conferencias, (68), 13-43, Madrid, Ministerio de Defensa.Mazarredo Zalazar, J. (1790): Lecciones de navegación para el uso de las compañías de guardias marinas. Isla de León, Imprenta de su Academia.Navarro Brotons, V. (2014): Disciplinas, saberes y prácticas. Filosofía natural, matemáticas y astronomía en la sociedad española de la época moderna, Valencia, Universitat de Vàlencia.Navarro Loidi, J.M. (2008): El número e en los textos matemáticos españoles del siglo xviii. “Quaderns d’història de l’enginyeria”, 2008, vol. 9, p. 145-166.Pintos Amengual, G. (2020): Evolución del cálculo de la latitud por la altura meridiana incluido en los textos para la formación de los pilotos de la Carrera de Indias en tiempo de los Austrias, Naveg@mérica. Revista electrónica editada por la Asociación Española de Americanistas, (25).— (2021a): La transición a la navegación astronómica científica y la formación de los pilotos españoles, siglo xvi-xviii. Tesis doctoral. Escuela de Ingenieros de Bilbao.— (2021b): La influencia del Museo Matemático de Bilbao (1742) y las “Lecciones náuticas” (1756) de Miguel Archer, en el tránsito del “arte de navegar” a la “navegación astronómica científica” en la formación de los pilotos españoles, Llull: Revista de la Sociedad Española de Historia de las Ciencias y de las Técnicas, Año 2021, Vol. 44, Número 88.Rey Pastor, J. (1970): La ciencia y técnica en el descubrimiento de América, Buenos Aires, Espasa Calpe.Salvá, M. y Sainz de Baranda, P. (1852): Colección de documentos inéditos para la historia de España, Madrid, Imprenta de la Viuda de Calero, Volumen 21.Sánchez Martínez, A. (2010): La voz de los artesanos en el Renacimiento científico. Cosmógrafos y cartógrafos en el preludio de la nueva filosofía natural. Arbor Ciencia, Pensamiento y Cultura, May./jun., 2010, vol. CLXXXVI, p. 456. Sánchez Reciente, J. (1749): Tratado de navegación y theorica, y practica fegun el orden, y Methodo, con que fe enfeña en el Real Colegio Seminario de Sr. S. Telmo, extramuros de la Ciudad de Sevilla. Sevilla, Imprenta Caftellana.Sellés García, M. A. (2000): Navegación astronómica en la España del siglo xviii, Madrid, Universidad Nacional de Educación a Distancia.Sobel, D. (1998): Longitud, Madrid: Debate, S.A.Vázquez Lijó, J. M. (2006): La Matrícula de Mar y sus repercusiones en la Galicia del siglo xviii. Oh: Obradoiro De Historia Moderna, (15). https://doi.org/10.15304/ohm.15.919 Vázquez Queipo, V. (1967): Tablas de los logaritmos vulgares de los número desde 1 hasta 20 000 y de las líneas trigonométricas, Madrid, librería y casa editorial Hernando, S.A.Zaragoza y Vilanova, B. J. de. (1675): Esfera en común celeste y terráquea, Madrid, Juan Martín del Barrio.
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Zhou, Xin, Thomas Hutsch, Lars Penter, Holger Rudolph, Steffen Ihlenfeldt e Thomas Weißgärber. "Experimental and numerical analysis of damping behavior of iron graphite composite in machine tool joint". Journal of Vibration and Control, 14 novembre 2022, 107754632211383. http://dx.doi.org/10.1177/10775463221138379.
Testo completoAbstract (sommario):
Iron graphite (FeGr) composite is a potential design material for machine tools to increase vibration damping without additional energy. Previous studies focused on the isolated composite’s properties rather than their damping effect as a passive damper to assembled components. There is currently no effective model using real mode superposition (RMS) method for demonstrating the damping behavior of FeGr composites in a multi-material structure. This paper presents a local damping description for a finite element model with RMS assuming constant loss factor for all modes to simulate the damping behavior of FeGr composites and their contribution to system damping and a test rig to identify the model parameters for typical machine tool boundary conditions. The influence of FeGr spacers with 0, 20%, 40%, and 60% graphite content on eigenfrequency and on damping of the test rig was measured, and the results were used to identify the damping model. The agreement of eigenfrequencies and damping ratio between measurement and simulation proves the effectiveness of the parameterized damping model predicting the mode-dependent damping behavior of FeGr in machine tool joints. The material analysis indicates that increasing the graphite content of FeGr composites from 0 to 60% amplifies the system damping from 0.03% to 0.6% at first bending mode. The interface pressure in a tightly fastened FeGr joint affects the system damping significantly. When designing machine tools, the surface condition of FeGr composite cannot be overlooked. FeGr dominates system damping and shows better damping performance at high vibration amplitudes.
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Kang, Ting, Huaizhi Wang, Ting Wu, Jianchun Peng e Hui Jiang. "Solar irradiance prediction based on self-attention recursive model network". Frontiers in Energy Research 10 (5 settembre 2022). http://dx.doi.org/10.3389/fenrg.2022.977979.
Testo completoAbstract (sommario):
In recent years, with the continued development and popularity of sustainable energy sources and the increasing utilization of solar energy, accurate solar radiation prediction has become important. In this paper, we propose a new model based on deep learning, Feature-enhanced Gated Recurrent Unit, hereafter referred to as FEGRU, for solar radiation prediction. This model takes the source data with one-dimensional convolution and self-attention to feature attention and processes the data features, and then GRU performs feature extraction on solar irradiance data. Finally, the data dimensionality is transformed by a fully connected layer. The main advantage of FEGRU is that it does not require auxiliary data, but only time series data of solar irradiance can be used for good solar irradiance prediction. Our experiments with solar irradiance samples in Lyon, France, show that our model has better prediction results than the baseline model.
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Ibrahim, Fabio, e Tom Kattenberg. "Die heuristische Gefährdungsbeurteilung – ein Fortbildungsansatz zur Verbesserung der Polizeiarbeit im Umgang mit Personen in psychischen Ausnahmezuständen". Forensische Psychiatrie, Psychologie, Kriminologie, 1 febbraio 2024. http://dx.doi.org/10.1007/s11757-023-00818-z.
Testo completoAbstract (sommario):
ZusammenfassungZiel dieser Übersichtsarbeit ist die Diskussion des polizeilichen Umgangs mit psychisch erkrankten Personen und Personen in psychischen Ausnahmezuständen. Die Themenrelevanz wird anhand praktischer Beispiele sowie der Darstellung aktueller Forschungsergebnisse und -kontroversen aufgezeigt. Aufbauend auf der Schlussfolgerung von Lorey und Fegert (2021) zur notwendigen Verbesserung der polizeilichen Fortbildung werden Konzeptionsinhalte einer heuristischen Gefährdungsbeurteilung im Umgang mit Personen in psychischen Ausnahmezuständen abgeleitet. Ein dienststellenübergreifendes Ausbildungskonzept, mit vereinheitlichten Begrifflichkeiten und Handlungsempfehlungen, könnte den Polizist:innen mehr Handlungssicherheit ermöglichen, das Eskalationspotenzial verringern und den Einsatzerfolg erhöhen.
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Darras, Gilles. "Hans Feger (Hg.), Friedrich Schiller – Die Realität des Idealisten. 2006". Arbitrium 27, n. 1 (gennaio 2009). http://dx.doi.org/10.1515/arbi.2009.021.
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Brennan, Susan. "Blind Swimmers". Calabash: a Journal of Caribbean Arts and Letters 3, n. 1 (2004). http://dx.doi.org/10.33682/bw8a-fegr.
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