bluuebunny/crossref_metadata_2025_split huggingface dataset:
MONARCH 2: Abemaciclib in Combination With Fulvestrant in Women With HR+/HER2− Advanced Breast Cancer Who Had Progressed While Receiving Endocrine Therapy
Authors: Sledge George W. , Toi Masakazu , Neven Patrick , Sohn Joohyuk , Inoue Kenichi , Pivot Xavier , Burdaeva Olga , Okera Meena , Masuda Norikazu , Kaufman Peter A. , Koh Han , Grischke Eva-Maria , Frenzel Martin , Lin Yong , Barriga Susana , Smith Ian C. , Bourayou Nawel , Llombart-Cussac Antonio 
Published: June 2017

Purpose MONARCH 2 ( ClinicalTrials.gov identifier: NCT02107703) compared the efficacy and safety of abemaciclib, a selective cyclin-dependent kinase 4 and 6 inhibitor, plus fulvestrant with fulvestrant alone in patients with advanced breast cancer (ABC). Patients and Methods MONARCH 2 was a global, double-blind, phase III study of women with hormone receptor-positive and human epidermal growth factor receptor 2-negative ABC who had progressed while receiving neoadjuvant or adjuvant endocrine therapy (ET), ≤ 12 months from the end of adjuvant ET, or while receiving first-line ET for metastatic disease. Patients were randomly assigned 2:1 to receive abemaciclib or placebo (150 mg twice daily) on a continuous schedule and fulvestrant (500 mg, per label). The primary end point was investigator-assessed progression-free survival (PFS), and key secondary end points included overall survival, objective response rate (ORR), duration of response, clinical benefit rate, quality of life, and safety. Results Between August 2014 and December 2015, 669 patients were randomly assigned to receive abemaciclib plus fulvestrant (n = 446) or placebo plus fulvestrant (n = 223). Abemaciclib plus fulvestrant significantly extended PFS versus fulvestrant alone (median, 16.4 v 9.3 months; hazard ratio, 0.553; 95% CI, 0.449 to 0.681; P < .001). In patients with measurable disease, abemaciclib plus fulvestrant achieved an ORR of 48.1% (95% CI, 42.6% to 53.6%) compared with 21.3% (95% CI, 15.1% to 27.6%) in the control arm. The most common adverse events in the abemaciclib versus placebo arms were diarrhea (86.4% v 24.7%), neutropenia (46.0% v 4.0%), nausea (45.1% v 22.9%), and fatigue (39.9% v 26.9%). Conclusions Abemaciclib at 150 mg twice daily plus fulvestrant was effective, significantly improving PFS and ORR and demonstrating a tolerable safety profile in women with hormone receptor-positive and human epidermal growth factor receptor 2-negative ABC who progressed while receiving ET.
Low-intensity pulsed ultrasound promotes cell motility through vinculin-controlled Rac1 GTPase activity
Authors: Atherton Paul , Lausecker Franziska , Harrison Andrew , Ballestrem Christoph 
Published: June 2017

ABSTRACT
Low-intensity pulsed ultrasound (LIPUS) is a therapy used clinically to promote healing. Using live-cell imaging we show that LIPUS stimulation, acting through integrin-mediated cell-matrix adhesions, rapidly induces Rac1 activation associated with dramatic actin cytoskeleton rearrangements. Our study demonstrates that the mechanosensitive focal adhesion (FA) protein vinculin, and both focal adhesion kinase (FAK, also known as PTK2) and Rab5 (both the Rab5a and Rab5b isoforms) have key roles in regulating these effects. Inhibiting the link of vinculin to the actin-cytoskeleton abolished LIPUS sensing. We show that this vinculin-mediated link was not only critical for Rac1 induction and actin rearrangements, but was also important for the induction of a Rab5-dependent increase in the number of early endosomes. Expression of dominant-negative Rab5, or inhibition of endocytosis with dynasore, also blocked LIPUS-induced Rac1 signalling events. Taken together, our data show that LIPUS is sensed by cell matrix adhesions through vinculin, which in turn modulates a Rab5-Rac1 pathway to control ultrasound-mediated endocytosis and cell motility. Finally, we demonstrate that a similar FAK-Rab5-Rac1 pathway acts to control cell spreading upon fibronectin.
Secreted tissue inhibitor of matrix metalloproteinase restricts trans-synaptic signaling to coordinate synaptogenesis
Authors: Shilts Jarrod , Broadie Kendal 
Published: June 2017

ABSTRACT
Synaptogenesis is coordinated by trans-synaptic signals that traverse the specialized synaptomatrix between presynaptic and postsynaptic cells. Matrix metalloproteinase (Mmp) activity sculpts this environment, balanced by secreted tissue inhibitors of Mmp (Timp). Here, we use the simplified Drosophila melanogaster matrix metalloproteome to test the consequences of eliminating all Timp regulatory control of Mmp activity at the neuromuscular junction (NMJ). Using in situ zymography, we find Timp limits Mmp activity at the NMJ terminal and shapes extracellular proteolytic dynamics surrounding individual synaptic boutons. In newly generated timp null mutants, NMJs exhibit architectural overelaboration with supernumerary synaptic boutons. With cell-targeted RNAi and rescue studies, we find that postsynaptic Timp limits presynaptic architecture. Functionally, timp null mutants exhibit compromised synaptic vesicle cycling, with activity that is lower in amplitude and fidelity. NMJ defects manifest in impaired locomotor function. Mechanistically, we find that Timp limits BMP trans-synaptic signaling and the downstream synapse-to-nucleus signal transduction. Pharmacologically restoring Mmp inhibition in timp null mutants corrects bone morphogenetic protein (BMP) signaling and synaptic properties. Genetically restoring BMP signaling in timp null mutants corrects NMJ structure and motor function. Thus, Timp inhibition of Mmp proteolytic activity restricts BMP trans-synaptic signaling to coordinate synaptogenesis.
Ο ρόλος του μέντορα στο ελληνικό εκπαιδευτικό σύστημα: διερεύνηση απόψεων εκπαιδευτικών πρωτοβάθμιας εκπαίδευσης νομού Θεσσαλονίκης για την αναγκαιότητα εφαρμογής του θεσμού
Authors: Παππά Ελένη , Ιορδανίδης Γεώργιος 
Published: June 2017

Στόχος της παρούσας έρευνας είναι η διερεύνηση του τρόπου με τον οποίο εκπαιδευτικοί της Πρωτοβάθμιας Εκπαίδευσης αντιλαμβάνονται το ρόλο του μέντορα (mentoring) ως υποστηρικτική δομή. Συνάμα, προσανατολίζεται στη διερεύνηση της άποψης των εκπαιδευτικών για την αναγκαιότητα εισαγωγής του θεσμού, τον πιθανό βαθμό ανταπόκρισής του στις ανάγκες των εκπαιδευτικών και τις προϋποθέσεις αποτελεσματικής εφαρμογής του. Συμμετέχοντες στην έρευνα ήταν 215 εκπαιδευτικοί πρωτοβάθμιας εκπαίδευσης. Η στατιστική επεξεργασία των δεδομένων του ερωτηματολογίου έγινε με τη χρήση του στατιστικού λογισμικού S.P.S.S. 22. Έγινε έλεγχος όλων των μεταβλητών με βάση το φύλο και τη διδακτική/εργασιακή εμπειρία. Επιπρόσθετα, οι προϋποθέσεις εφαρμογής του θεσμού (Ενότητα Ε1) ελέγχθηκαν και σε σχέση με τα τυπικά και επιπρόσθετα προσόντα. Στη συνέχεια, πραγματοποιήθηκε ενδελεχής ανάλυση με βάση τα ευρήματα των πινάκων συνάφειας και των αναδυόμενων συσχετίσεων. Τα ερευνητικά αποτελέσματα ανέδειξαν ότι οι εκπαιδευτικοί συναινούν στην εφαρμογή του θεσμού με ένα πιλοτικό πρόγραμμα, που αξιοποιεί ερευνητικά πορίσματα και επιτυχημένες διαρθρώσεις προγραμμάτων εφαρμοσμένων στο εξωτερικό, διενεργώντας τις απαραίτητες προσαρμογές στα ελληνικά δεδομένα αλλά καταγράφηκε μια δυσπιστία κυρίως από το έμπειρο εκπαιδευτικό προσωπικό. Η ενσωμάτωση του θεσμού στις σχολικές μονάδες διαφαίνεται ότι εξυπηρετεί την εξατομικευμένη αντιμετώπιση των αναγκών του εκπαιδευτικού πληθυσμού. Συνάμα, αναδύεται ότι το καθοδηγητικό πρόγραμμα ενέχει τη δυναμική ανάπτυξης συνεργατικής επαγγελματικής κουλτούρας με απόρροια τη διάχυση της ωφέλειας στους εμπλεκόμενους της εκπαιδευτικής διαδικασίας.
Report of the Nomenclature Committee for Bryophytes: 13
Authors: Klazenga Niels 
Published: June 2017

SummaryThe following four names of bryophytes are recommended for conservation: Hypnum uncinatulum against H. pseudocupressiforme, Tortula angustata against Syrrhopodon crispus, Selenia Nutt. against Selenia Hill and Haplocladium (Müll. Hal.) Müll. Hal. against Haplocladium Nägeli. The following three names are not recommended for conservation: Globulina boliviana against Trichostomum brunneum, Bartramia curvata against B. fontanoides and Jungermania ornithopoides with a conserved spelling (“ornithopodioides”). The Committee failed to reach a decision on the conservation of Gertrudia validinervis against Barbula uncinicoma. Futhermore, the Committee considers Rauiella Reimers and Rauhiella Pabst & Braga not confusable.
Report on corrections and future considerations for Appendices II–VIII of the International Code of Nomenclature for algae, fungi, and plants
Authors: Wiersema John H. , May Tom W. , Turland Nicholas J. 
Published: June 2017

AbstractFor the first time, the main text and Appendices II–VIII of the International Code of Nomenclature were separately published following decisions of the 2011 Melbourne Nomenclature Section, which contributed to the subsequent development of an online resource capable of producing the Appendices in real time. These developments, and others pertaining to newly generated lists of fungal names, raise issues outlined in this paper that should be discussed by the upcoming 2017 Shenzhen Nomenclature Section. An accounting of all corrections and additions to the online version (based on the hardcopy version) of Melbourne Appendices II–VIII is also appended.
Unraveling relationships in the morphologically diverse and taxonomically challenging “justicioid” lineage (Acanthaceae: Justicieae)
Authors: Kiel Carrie A. , Daniel Thomas F. , Darbyshire Iain , McDade Lucinda A. 
Published: June 2017

AbstractThis is the first study in Acanthaceae to provide a robust and well‐sampled phylogenetic framework for the “justicioid” lineage (Acanthaceae: Acanthoideae: Justicieae), a clade that includes at least 1000 species that together occupy essentially the entire distributional range of the family as a whole. Species are morphologically diverse and occupy a wide variety of habitats. Although much progress has been made in understanding phylogenetic relationships within Acanthaceae, well‐sampled phylogenetic studies are lacking for justicioids. DNA sequence data from six regions for 178 accessions from across the entire lineage were used to test monophyly and validity of 17 putative genera of justicioids on a global scale. Included among these genera is the species‐rich genus Justicia for which we evaluate the current morphology‐based classification with a focus on Old World taxa. Our results strongly support monophyly of New World justicioids, including all New World species of Justicia plus species assigned to at least five other smaller genera. Further, with a greatly expanded taxon sample, we confirm our earlier unexpected result that Diclipterinae are embedded within justicioids. As traditionally circumscribed, Diclipterinae lack the morphological traits that mark justicioids and thus had not previously been associated with that group. This study further extends this unexpected result by placing a number of Old World justicioids in a clade that is sister to Diclipterinae. Although some genera of justicioids, notably of Diclipterinae, are monophyletic, Justicia is grossly polyphyletic. We explore these results by examining the diagnostic utility of morphological characters for major clades with a focus on inflorescences, androecia, pollen and seeds. We further use our results as context for documenting evolutionary patterns of floral traits and pollinator relationships, as well as biogeographic patterns, across this species‐rich and diverse clade.
Europas Hoffnung auf den Brennspiegel im 13. Jahrhundert
Authors: Lohrmann Dietrich 
Published: June 2017

ZusammenfassungBrennspiegel mit möglichst starker Konzentration der reflektierten Strahlen auf einen Brennpunkt faszinierten die Wissenschaft seit der Antike. Sie trafen schon im Europa des 13. Jahrhunderts auf ein nachhaltiges Interesse. Mindestens fünf bedeutende Autoren, zwei Engländer, ein Pikarde, ein Flame, ein „Thuringo-Polonus“ und ein Pariser Magister aus dem Limousin, beschäftigten sich mit der Theorie der Reflexion, verglichen die verschiedenen Arten von Spiegeln nach ihrer Leistung und bauten sie auch in der Praxis. Der Anstoß zu diesen Forschungen und Experimenten ging aus von der lateinischen Übersetzung eines ins Latein übersetzten Traktates des großen arabischen Gelehrten Ibn al-Haitam / Alhazen (um 1000). Ein enger Vertrauter des künftigen Papstes Clemens IV., Roger Bacon, unterstützte 1266–1268 den Bau eines ersten westeuropäischen Brennspiegels durch den pikardischen Ingenieur Pierre de Maricourt. Durch Bacon gelangten wichtige Informationen an die päpstliche Kurie. Sie war damals ein wichtiges Zentrum auch der Naturforschung. Außer der Hoffnung auf praktische Nutzung konzentrierter Sonnenwärme in verschiedenen Gewerben faszinierte der Gedanke eines militärischen Einsatzes gegen die Muslime im Heiligen Land. Das Interesse an Brennspiegeln erlahmte nie, es ist in Form der CSP-Technologie von großer aktueller Bedeutung, leidet aber erneut unter vorherrschend finanzieller Bewertung.
Effect of Cooking Conditions on Quality Characteristics of Confit Cod: Prediction by MRI
Authors: Pérez Palacios Trinidad , Caballero Daniel , Bravo Sara , Mir Bel Jorge , Antequera Teresa 
Published: June 2017

Abstract
This study evaluates the effect of low temperature (60, 64 and 68 °C) and different times (15 and 20 min) of cooking on physicochemical and sensory characteristics of confit cod and analyzes confit cod in a non-destructive way by means of magnetic resonance imaging (MRI) and computer vision techniques. Higher scores for acceptability and flavor in 60 °C–20 min and 64 °C–20 min samples and some physicochemical differences were found. These results allow distinguishing four groups of confit cods as a function of cooking conditions – 60 °C–15 min/68 °C–15 min/68 °C–20 min/60 °C–20 min, 64 °C–15 min, 64 °C–20 min – and proposing to cook confit cod at 60–64 °C during 20 min. Prediction by means of computational texture features from MRI gave moderate-to-good correlation (0.6–0.75) for six quality attributes and very good-to-excellent relationship (0.75–1) for other six. Thus, computational texture features seem to be appropriate to determine the quality attributes of confit cod in a non-destructive way.
Säkular – mehr als „nichtreligiös“?
Authors: Kalbheim Boris , Ziebertz Hans-Georg 
Published: June 2017

AbstractThere is hardly an autonomous description of those who do not belong to a religious denomination and who don't regard themselves as religious in a traditional way. The terms “non-denominational” and “non-religious” implicate a dissociation from the historically traditional concept of religion, but they do not offer any alternative ideological communalities. This article discusses the option of a “secular worldview” and investigates whether religious and non-religious respondents differ in their attitudes on selected human rights – and if so, to what extent. The empirical study (N=2244) shows that human rights are supported by all young people, athough in some cases with differing emphases. In basic terms, we can discern a common worldview or ‘Weltanschauung’ of secular respondents. This is recognizable as an approval of the intrinsic value of the Other as well as a recognition of norms set by public society.
Effect on Cs removal of solid-phase metal oxidation in metal ferrocyanides
Authors: Lee Keun-Young , Kim Jimin , Oh Maengkyo , Lee Eil-Hee , Kim Kwang-Wook , Chung Dong-Yong , Moon Jei-Kwon 
Published: June 2017

Abstract
Metal ferrocyanides (MFCs) have been studied for many years and are regarded as efficient adsorbents for the selective removal of radioactive cesium (Cs) from contaminated aqueous solutions. Although their efficiency has been demonstrated, various investigations on the physicochemical, thermal, and radiological stability of the solids of MFCs are required to enhance the applicability of MFCs in the treatment process. We observed that the Cs adsorption efficiencies of cobalt and nickel ferrocyanides decreased as their aging period increased, while the Cs adsorption efficiencies of copper and zinc ferrocyanides did not decrease. The tendencies of these ferrocyanides were accelerated by exposure of the solids at a higher temperature for a longer time. Our comprehensive analyses demonstrated that only the oxidizable metals in the MFCs can be oxidized by aging time and increasing temperature; also, this affects the Cs removal efficiency by decreasing the exchangeable sites in the solids. The chemical stability of MFCs is very important for the optimization of the synthesis and storage conditions.
Differential regulation of monocarboxylate transporter 8 expression in thyroid cancer and hyperthyroidism
Authors: Badziong Julia , Ting Saskia , Synoracki Sarah , Tiedje Vera , Brix Klaudia , Brabant Georg , Moeller Lars Christian , Schmid Kurt Werner , Fuhrer Dagmar , Zwanziger Denise 
Published: June 2017

Objective
Thyroid hormone (TH) transporters are expressed in thyrocytes and most play a role in TH release. We asked whether expression of the monocarboxylate transporter 8 (MCT8) and the L-type amino acid transporters LAT2 and LAT4 is changed with thyrocyte dedifferentiation and in hyperfunctioning thyroid tissues.

Design and methods
Protein expression and localization of transporters was determined by immunohistochemistry in human thyroid specimen including normal thyroid tissue (NT, n = 19), follicular adenoma (FA, n = 44), follicular thyroid carcinoma (FTC, n = 45), papillary thyroid carcinoma (PTC, n = 40), anaplastic thyroid carcinoma (ATC, n = 40) and Graves’ disease (GD, n = 50) by calculating the ‘hybrid’ (H) score. Regulation of transporter expression was investigated in the rat follicular thyroid cell line PCCL3 under basal and thyroid stimulating hormone (TSH) conditions.

Results
MCT8 and LAT4 were localized at the plasma membrane, while LAT2 transporter showed cytoplasmic localization. MCT8 expression was downregulated in benign and malignant thyroid tumours as compared to NT. In contrast, significant upregulation of MCT8, LAT2 and LAT4 was found in GD. Furthermore, a stronger expression of MCT8 was demonstrated in PCCL3 cells after TSH stimulation.

Conclusions
Downregulation of MCT8 in thyroid cancers qualifies MCT8 as a marker of thyroid differentiation. The more variable expression of LATs in distinct thyroid malignancies may be linked with other transporter properties relevant to altered metabolism in cancer cells, i.e. amino acid transport. Consistent upregulation of MCT8 in GD is in line with increased TH release in hyperthyroidism, an assumption supported by our in vitro results showing TSH-dependent upregulation of MCT8.
Evolving Mistranslating tRNAs Through a Phenotypically Ambivalent Intermediate inSaccharomyces cerevisiae
Authors: Berg Matthew D , Hoffman Kyle S , Genereaux Julie , Mian Safee , Trussler Ryan S , Haniford David B , O’Donoghue Patrick , Brandl Christopher J 
Published: June 2017

AbstractIt is increasingly apparent that the genetic code is not static and that organisms use variations in the genetic code for selective advantage. Berg...The genetic code converts information from nucleic acid into protein. The genetic code was thought to be immutable, yet many examples in nature indicate that variations to the code provide a selective advantage. We used a sensitive selection system involving suppression of a deleterious allele (tti2-L187P) in Saccharomyces cerevisiae to detect mistranslation and identify mechanisms that allow genetic code evolution. Though tRNASer containing a proline anticodon (UGG) is toxic, using our selection system we identified four tRNASer UGG variants, each with a single mutation, that mistranslate at a tolerable level. Mistranslating tRNALeu UGG variants were also obtained, demonstrating the generality of the approach. We characterized two of the tRNASer UGG variants. One contained a G26A mutation, which reduced cell growth to 70% of the wild-type rate, induced a heat shock response, and was lost in the absence of selection. The reduced toxicity of tRNASer UGG-G26A is likely through increased turnover of the tRNA, as lack of methylation at G26 leads to degradation via the rapid tRNA decay pathway. The second tRNASer UGG variant, with a G9A mutation, had minimal effect on cell growth, was relatively stable in cells, and gave rise to less of a heat shock response. In vitro, the G9A mutation decreases aminoacylation and affects folding of the tRNA. Notably, the G26A and G9A mutations were phenotypically neutral in the context of an otherwise wild-type tRNASer. These experiments reveal a model for genetic code evolution in which tRNA anticodon mutations and mistranslation evolve through phenotypically ambivalent intermediates that reduce tRNA function.
Pharmacological Inhibition of the DNA Damage Checkpoint Prevents Radiation-Induced Oocyte Death
Authors: Rinaldi Vera D , Hsieh Kristin , Munroe Robert , Bolcun-Filas Ewelina , Schimenti John C 
Published: June 2017

Abstract
Ovarian function is directly correlated with survival of the primordial follicle reserve. Women diagnosed with cancer have a primary imperative of treating the cancer, but since the resting oocytes are hypersensitive to the DNA-damaging modalities of certain chemo- and radiotherapeutic regimens, such patients face the collateral outcome of premature loss of fertility and ovarian endocrine function. Current options for fertility preservation primarily include the collection and cryopreservation of oocytes or in vitro-fertilized oocytes, but this necessitates a delay in cancer treatment and additional assisted reproductive technology procedures. Here, we evaluated the potential of pharmacological preservation of ovarian function by inhibiting a key element of the oocyte DNA damage checkpoint response, checkpoint kinase 2 (CHK2; CHEK2). Whereas nonlethal doses of ionizing radiation (IR) eradicate immature oocytes in wild-type mice, irradiated Chk2−/− mice retain their oocytes and, thus, fertility. Using an ovarian culture system, we show that transient administration of the CHK2 inhibitor 2-(4-(4-chlorophenoxy)phenyl)-1H-benzimidazole-5-carboxamide-hydrate (“CHK2iII”) blocked activation of the CHK2 targets TRP53 and TRP63 in response to sterilizing doses of IR, and preserved oocyte viability. After transfer into sterilized host females, these ovaries proved functional and readily yielded normal offspring. These results provide experimental evidence that chemical inhibition of CHK2 is a potentially effective treatment for preserving the fertility and ovarian endocrine function of women exposed to DNA-damaging cancer therapies such as IR.
Continuous-Flow Hydrogenation of 4-Phenylpyridine to 4-Phenylpiperidine with Integrated Product Isolation Using a CO2 Switchable System
Authors: Barwinski Bernhard , Migowski Pedro , Gallou Fabrice , Franciò Giancarlo , Leitner Walter 
Published: June 2017

Abstract
A process comprising a continuous-flow hydrogenation reaction integrated with selective water-organic solvent biphasic extraction using CO2 as molecular switch to control partitioning was devised for the synthesis of arylpiperidines from arylpyridines. The selective hydrogenation of 4-phenylpyridine using heterogeneous carbon-supported metal catalysts was chosen as model reaction. A design-of-experiment approach was used for the identification of suitable reaction conditions under continuous-flow operation. A maximum selectivity for 4-phenylpiperidine of 96% was achieved at 87% conversion suppressing the deep hydrogenation to 4-cyclohexylpiperidine almost completely (≤5%). The higher basicity of piperidines over pyridines was exploited for selective and reversible protonation of the product upon pressurization with CO2 separating it quantitatively from the remaining starting material in a water-EtOAc biphasic system. This concept enabled a fully integrated and a salt-free synthetic process using a standard Pd/C catalyst for the hydrogenation coupled with the CO2-triggered isolation of the desired product 4-phenylpiperidine in 81% yield and 98% purity.