bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abscisic acid form, concentration, and application timing influence phenology and bud cold hardiness in Merlot grapevines
Authors: Bowen Pat , Shellie Krista C. , Mills Lynn , Willwerth Jim , Bogdanoff Carl , Keller Markus 
Published: May 2016

The effects of abscisic acid (ABA) form, concentration, and application timing on bud cold hardiness, phenology, and fruiting performance of Merlot grapevines (Vitis vinifera) were evaluated in a three-year field trial with site locations in British Columbia and Ontario, Canada, and in Washington and Idaho, United States. Solutions containing natural S-ABA (ABAN) and a purported long-lived ABA analogue 8'-acetylene ABA (ABAA) at differing concentrations were applied to the vine canopy at veraison or post-harvest. Postharvest foliar applications of ABANat concentrations greater than or equal to 5000 ppm tended to advance leaf abscission and increase autumn bud cold hardiness. Postharvest foliar applications of ABAAat 1000 ppm tended to delay budbreak in the spring following application and increase spring bud cold hardiness. Fruit yield and basic composition were affected little by the ABA treatments. Bud hardiness was enhanced by ABANmostly in autumn and by ABAAmostly in the spring, indicating that the suitability of ABA forms for reducing bud damage would depend on when injurious cold events are more likely.
Thinking about the geosciences in their religious/philosophical context
Authors: Kölbl-Ebert Martina 
Published: May 2016

Abstract

At some stage in their past, all advanced civilizations have developed some sort of mining industry and a mythical approach to the explanation of various geological phenomena. Nevertheless, the geosciences per se developed in Europe, as part of natural philosophy and from there spread throughout the globe. Why Europe was the cradle of this type of natural philosophy, which led to modern science, can only be understood if we take into account not only the history of science, but a more general history of human intellectual accomplishments, including a history of theology and philosophy. This paper endeavours to trace the philosophical/religious settings that either furthered or hampered science. Historically, geology and palaeontology have been fashionable sciences from their first tentative beginnings in Renaissance times to the late nineteenth century. They were popular and of public interest as long as they bore not only scientific fruits, but also had a certain feedback on the contemporary world view. This paper outlines these interdependencies between the two
magisteria
of science and religion and gives an insight into the contemporary relationship between geology and religion.
Dicer Elicits Paclitaxel Chemosensitization and Suppresses Cancer Stemness in Breast Cancer by Repressing AXL
Authors: Chang Ting-Yu , Chen Hsin-An , Chiu Ching-Feng , Chang Yi-Wen , Kuo Tsang-Chih , Tseng Po-Chun , Wang Weu , Hung Mien-Chie , Su Jen-Liang 
Published: May 2016

Abstract
Paclitaxel is a standard-of-care chemotherapy for breast cancer, despite the increasing recognition of its poor effectiveness in the treatment of patients with advanced disease. Here, we report that adenovirus-type 5 E1A-mediated elevation of the miRNA-processing enzyme Dicer is sufficient to enhance paclitaxel sensitization and reduce cancer stem-like cell properties in this setting. Elevating Dicer expression increased levels of the AXL kinase targeting miRNA miR-494, thereby repressing AXL expression to increase paclitaxel sensitivity. We found that Dicer expression was regulated at the transcription level by E1A, through activation of an MAPK14/CEBPα pathway. Our findings define a mechanism of E1A-mediated chemosensitization for paclitaxel, which is based upon the suppression of breast cancer stem-like cells, with potential implications for the diagnosis and treatment of breast cancer patients. Cancer Res; 76(13); 3916–28. ©2016 AACR.
A Novel Bispecific Antibody Targeting EGFR and cMet Is Effective against EGFR Inhibitor–Resistant Lung Tumors
Authors: Moores Sheri L. , Chiu Mark L. , Bushey Barbara S. , Chevalier Kristen , Luistro Leopoldo , Dorn Keri , Brezski Randall J. , Haytko Peter , Kelly Thomas , Wu Sheng-Jiun , Martin Pauline L. , Neijssen Joost , Parren Paul W.H.I. , Schuurman Janine , Attar Ricardo M. , Laquerre Sylvie , Lorenzi Matthew V. , Anderson G. Mark 
Published: May 2016

Abstract
Non–small cell lung cancers (NSCLC) with activating EGFR mutations become resistant to tyrosine kinase inhibitors (TKI), often through second-site mutations in EGFR (T790M) and/or activation of the cMet pathway. We engineered a bispecific EGFR-cMet antibody (JNJ-61186372) with multiple mechanisms of action to inhibit primary/secondary EGFR mutations and the cMet pathway. JNJ-61186372 blocked ligand-induced phosphorylation of EGFR and cMet and inhibited phospho-ERK and phospho-AKT more potently than the combination of single receptor–binding antibodies. In NSCLC tumor models driven by EGFR and/or cMet, JNJ-61186372 treatment resulted in tumor regression through inhibition of signaling/receptor downmodulation and Fc-driven effector interactions. Complete and durable regression of human lung xenograft tumors was observed with the combination of JNJ-61186372 and a third-generation EGFR TKI. Interestingly, treatment of cynomolgus monkeys with JNJ-61186372 resulted in no major toxicities, including absence of skin rash observed with other EGFR-directed agents. These results highlight the differentiated potential of JNJ-61186372 to inhibit the spectrum of mutations driving EGFR TKI resistance in NSCLC. Cancer Res; 76(13); 3942–53. ©2016 AACR.
Genomic Landscape Established by Allelic Imbalance in the Cancerization Field of a Normal Appearing Airway
Authors: Jakubek Yasminka , Lang Wenhua , Vattathil Selina , Garcia Melinda , Xu Li , Huang Lili , Yoo Suk-Young , Shen Li , Lu Wei , Chow Chi-Wan , Weber Zachary , Davies Gareth , Huang Jing , Behrens Carmen , Kalhor Neda , Moran Cesar , Fujimoto Junya , Mehran Reza , El-Zein Randa , Swisher Stephen G. , Wang Jing , Fowler Jerry , Spira Avrum E. , Ehli Erik A. , Wistuba Ignacio I. , Scheet Paul , Kadara Humam 
Published: May 2016

Abstract
Visually normal cells adjacent to, and extending from, tumors of the lung may carry molecular alterations characteristics of the tumor itself, an effect referred to as airway field of cancerization. This airway field has been postulated as a model for early events in lung cancer pathogenesis. Yet the genomic landscape of somatically acquired molecular alterations in airway epithelia of lung cancer patients has remained unknown. To begin to fill this void, we sought to comprehensively characterize the genomic architecture of chromosomal alterations inducing allelic imbalance (AI) in the airway field of the most common type of lung tumors, non–small cell lung cancer (NSCLC). To do so, we conducted a genome-wide survey of multiple spatially distributed normal-appearing airways, multiregion tumor specimens, and uninvolved normal tissues or blood from 45 patients with early-stage NSCLC. We detected alterations in airway epithelia from 22 patients, with an increased frequency in NSCLCs of squamous histology. Our data also indicated a spatial gradient of AI in samples at closer proximity to the NSCLC. Chromosome 9 displayed the highest levels of AI and comprised recurrent independent events. Furthermore, the airway field AI included oncogenic gains and tumor suppressor losses in known NSCLC drivers. Our results demonstrate that genome-wide AI is common in the airway field of cancerization, providing insights into early events in the pathogenesis of NSCLC that may comprise targets for early treatment and chemoprevention. Cancer Res; 76(13); 3676–83. ©2016 AACR.
Novel ß-HPV49 Transgenic Mouse Model of Upper Digestive Tract Cancer
Authors: Viarisio Daniele , Müller-Decker Karin , Zanna Paola , Kloz Ulrich , Aengeneyndt Birgit , Accardi Rosita , Flechtenmacher Christa , Gissmann Lutz , Tommasino Massimo 
Published: May 2016

Abstract
The beta genus of human papillomaviruses (ß-HPV) includes approximately 50 different viral types that are subdivided into five species (ß-1 through ß-5). Nonmelanoma cancers may involve some ß-1 and ß-2 HPV types, but the biology of most ß-HPV types and their possible connections to human disease are still little characterized. In this study, we studied the effects of ß-3 type HPV49 in a novel transgenic (Tg) mouse model, using a cytokeratin K14 promoter to drive expression of the E6 and E7 genes from this virus in the basal skin epidermis and the mucosal epithelia of the digestive tract (K14 HPV49 E6/E7-Tg mice). Viral oncogene expression only marginally increased cellular proliferation in the epidermis of Tg animals, compared with wild-type littermates, and we observed no spontaneous tumor formation during their entire lifespan. However, we found that K14 HPV49 E6/E7-Tg mice were highly susceptible to upper digestive tract carcinogenesis upon initiation with 4-nitroquinoline 1-oxide (4NQO). This was a selective effect, as the same mice did not exhibit any skin lesions after chronic UV irradiation. Opposite results were observed in an analogous Tg model expressing the ß-2 HPV38 E6 and E7 oncogenes at the same anatomic sites. While these mice were highly susceptible to UV-induced skin carcinogenesis, as previously shown, they were little affected by 4NQO treatment. Overall, our findings highlight important differences in the biologic properties of certain ß-type HPV that affect their impact on carcinogenesis in an anatomic site-specific manner. Cancer Res; 76(14); 4216–25. ©2016 AACR.
BRAF Status in Personalizing Treatment Approaches for Pediatric Gliomas
Authors: Olow Aleksandra , Mueller Sabine , Yang Xiaodong , Hashizume Rintaro , Meyerowitz Justin , Weiss William , Resnick Adam C. , Waanders Angela J. , Stalpers Lukas J.A. , Berger Mitchel S. , Gupta Nalin , James C. David , Petritsch Claudia K. , Haas-Kogan Daphne A. 
Published: May 2016

AbstractPurpose: Alteration of the BRAF/MEK/MAPK pathway is the hallmark of pediatric low-grade gliomas (PLGGs), and mTOR activation has been documented in the majority of these tumors. We investigated combinations of MEK1/2, BRAFV600E and mTOR inhibitors in gliomas carrying specific genetic alterations of the MAPK pathway.Experimental Design: We used human glioma lines containing BRAFV600E (adult high-grade: AM-38, DBTRG, PLGG: BT40), or wild-type BRAF (pediatric high-grade: SF188, SF9427, SF8628) and isogenic systems of KIAA1549:BRAF-expressing NIH/3T3 cells and BRAFV600E-expressing murine brain cells. Signaling inhibitors included everolimus (mTOR), PLX4720 (BRAFV600E), and AZD6244 (MEK1/2). Proliferation was determined using ATP-based assays. In vivo inhibitor activities were assessed in the BT40 PLGG xenograft model.Results: In BRAFV600E cells, the three possible doublet combinations of AZD6244, everolimus, and PLX4720 exhibited significantly greater effects on cell viability. In BRAFWT cells, everolimus + AZD6244 was superior compared with respective monotherapies. Similar results were found using isogenic murine cells. In KIAA1549:BRAF cells, MEK1/2 inhibition reduced cell viability and S-phase content, effects that were modestly augmented by mTOR inhibition. In vivo experiments in the BRAFV600E pediatric xenograft model BT40 showed the greatest survival advantage in mice treated with AZD6244 + PLX4720 (P &lt; 0.01).Conclusions: In BRAFV600E tumors, combination of AZD6244 + PLX4720 is superior to monotherapy and to other combinatorial approaches. In BRAFWT pediatric gliomas, everolimus + AZD6244 is superior to either agent alone. KIAA1549:BRAF-expressing tumors display marked sensitivity to MEK1/2 inhibition. Application of these results to PLGG treatment must be exercised with caution because the dearth of PLGG models necessitated only a single patient-derived PLGG (BT40) in this study. Clin Cancer Res; 22(21); 5312–21. ©2016 AACR.
A New Class of Antibody–Drug Conjugates with Potent DNA Alkylating Activity
Authors: Miller Michael L. , Fishkin Nathan E. , Li Wei , Whiteman Kathleen R. , Kovtun Yelena , Reid Emily E. , Archer Katie E. , Maloney Erin K. , Audette Charlene A. , Mayo Michele F. , Wilhelm Alan , Modafferi Holly A. , Singh Rajeeva , Pinkas Jan , Goldmacher Victor , Lambert John M. , Chari Ravi V.J. 
Published: May 2016

Abstract
The promise of tumor-selective delivery of cytotoxic agents in the form of antibody–drug conjugates (ADC) has now been realized, evidenced by the approval of two ADCs, both of which incorporate highly cytotoxic tubulin-interacting agents, for cancer therapy. An ongoing challenge remains in identifying potent agents with alternative mechanisms of cell killing that can provide ADCs with high therapeutic indices and favorable tolerability. Here, we describe the development of a new class of potent DNA alkylating agents that meets these objectives. Through chemical design, we changed the mechanism of action of our novel DNA cross-linking agent to a monofunctional DNA alkylator. This modification, coupled with linker optimization, generated ADCs that were well tolerated in mice and demonstrated robust antitumor activity in multiple tumor models at doses 1.5% to 3.5% of maximally tolerated levels. These properties underscore the considerable potential of these purpose-created, unique DNA-interacting conjugates for broadening the clinical application of ADC technology. Mol Cancer Ther; 15(8); 1870–8. ©2016 AACR.
Diplogasteroides nix n. sp. (Nematoda: Diplogastridae), a cryptic species related to D. andrassyi, isolated from Monochamus urussovii (Coleoptera: Cerambycidae) from Hokkaido, Japan, with remarks on body surface structures
Authors: Kanzaki Natsumi , Sakamoto Hironori , Maehara Noritoshi 
Published: May 2016

Diplogasteroides nix n. sp. is described based on its typological characteristics, molecular profile and mating experiments. Diplogasteroides nix n. sp. is characterised by its tube-like stoma with three small dorsal teeth and two subventral ridges, spicule clearly ventrally bent at one-third from the anterior end, gubernaculum with a somewhat squared anterior end and sharply pointed distal end in a lateral view and nine pairs of genital papillae with an arrangement of ⟨v1, (v2, v3d)/v4, ad, ph, (v5, v6, v7), pd⟩, with the very small v5 and v6 protruding from socket-like bases, and v6 has a tripartite tip on males and well developed receptaculum seminis in females. In addition to the general morphological characters, the new species has several small secretory pore-like openings connected to secretory cells just beneath the surface cuticle (tentatively termed as ‘lateral glands’) in both males and females, and two pairs of button-like surface structures with clear internal connections in females. The new species is typologically and molecularly very similar to its tentatively assigned closest relative, D. andrassyi. These two species are morphologically almost identical, forming a cryptic species complex with some very minor morphological differences, e.g., the morphology of gubernaculum somewhat roundish squared vs clearly rounded anterior edge. Molecularly, these two species have identical small subunit sequences and have only 5 bp difference in the D2-D3 extension segments of the large subunit. However, the new species can be distinguished from D. andrassyi by mating incompatibility, yielding only F1 progenies in both male × female and female × male combinations. Biologically, these two species and another close relative were isolated from different carrier Monochamus longhorn beetles, i.e., D. nix n. sp., D. andrassyi and D. asiaticus have been found from M. urussovii, M. grandis and M. alternatus, respectively. However, because these beetle species share the distribution range and host tree species, further collection and identification are necessary to understand their host (carrier) interactions and specificity.
Tylenchid entomoparasites isolated from Spondylis buprestoides (L.) and Asemum striatum (L.) (Coleoptera: Cerambycidae)
Authors: Kanzaki Natsumi , Giblin-Davis Robin M. , Gonzalez Rafael , Trujillo Yasiel , Hajek Ann E. 
Published: May 2016

Tylenchid entomoparasites were isolated from two longhorn beetle species,Spondylis buprestoidesfrom Tsukuba, Japan, andAsemum striatumfrom Ithaca, Tompkins County, NY, USA. Parasitic females and juveniles were obtained fromS. buprestoides, where the female has a large body (5-6 mm long), clear stylet retracted into the body and degenerate anus and rectum, similar to some neotylenchids and allantonematids. By contrast, only stylet-bearing parasitic juveniles were found in eggs ofA. striatum, and detailed morphological analysis was not done for this isolate. These two isolates of parasites were molecularly characterised, and analysed for their phylogenetic status based on the small subunit of the ribosomal RNA gene. The phylogenetic inference suggested that the two parasitic nematodes are close to each other, and to thesiricidicolasuperspecies of the genusDeladenus,i.e., these two species andDeladenusform a well-supported clade. Because these two host beetle species belong to the same cerambycid subfamily (Spondylinae) from disparate locations, a subfamily-associated nematode parasite lineage may be revealed by further field surveys.
Accuracy of Rotational and Divergent Kinetic Energy Spectra Diagnosed from Flight-Track Winds
Authors: Bierdel Lotte , Snyder Chris , Park Sang-Hun , Skamarock William C. 
Published: May 2016

Abstract
Under assumptions of horizontal homogeneity and isotropy, one may derive relations between rotational or divergent kinetic energy spectra and velocities along one-dimensional tracks, such as might be measured by aircraft. Two recent studies, differing in details of their implementation, have applied these relations to the Measurement of Ozone and Water Vapor by Airbus In-Service Aircraft (MOZAIC) dataset and reached different conclusions with regard to the mesoscale ratio of divergent to rotational kinetic energy. In this study the accuracy of the method is assessed using global atmospheric simulations performed with the Model for Prediction Across Scales, where the exact decomposition of the horizontal winds into divergent and rotational components may be easily computed. For data from the global simulations, the two approaches yield similar and very accurate results. Errors are largest for the divergent component on synoptic scales, which is shown to be related to a very dominant rotational mode. The errors are, in particular, sufficiently small so that the mesoscale ratio of divergent to rotational kinetic energy can be derived correctly. The proposed technique thus provides a strong observational check of model results with existing large commercial aircraft datasets. The results do, however, show a significant dependence on the height and latitude ranges considered, and the disparate conclusions drawn from previous applications to MOZAIC data may result from the use of different subsets of the data.
Constraints on Climate Sensitivity from Space-Based Measurements of Low-Cloud Reflection
Authors: Brient Florent , Schneider Tapio 
Published: May 2016

AbstractPhysical uncertainties in global-warming projections are dominated by uncertainties about how the fraction of incoming shortwave radiation that clouds reflect will change as greenhouse gas concentrations rise. Differences in the shortwave reflection by low clouds over tropical oceans alone account for more than half of the variance of the equilibrium climate sensitivity (ECS) among climate models, which ranges from 2.1 to 4.7 K. Space-based measurements now provide an opportunity to assess how well models reproduce temporal variations of this shortwave reflection on seasonal to interannual time scales. Here such space-based measurements are used to show that shortwave reflection by low clouds over tropical oceans decreases robustly when the underlying surface warms, for example, by −(0.96 ± 0.22)% K−1 (90% confidence level) for deseasonalized variations. Additionally, the temporal covariance of low-cloud reflection with temperature in historical simulations with current climate models correlates strongly (r = −0.67) with the models’ ECS. Therefore, measurements of temporal low-cloud variations can be used to constrain ECS estimates based on climate models. An information-theoretic weighting of climate models by how well they reproduce the measured deseasonalized covariance of shortwave cloud reflection with temperature yields a most likely ECS estimate around 4.0 K; an ECS below 2.3 K becomes very unlikely (90% confidence).
Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma
Authors: Usmani Saad Z. , Weiss Brendan M. , Plesner Torben , Bahlis Nizar J. , Belch Andrew , Lonial Sagar , Lokhorst Henk M. , Voorhees Peter M. , Richardson Paul G. , Chari Ajai , Sasser A. Kate , Axel Amy , Feng Huaibao , Uhlar Clarissa M. , Wang Jianping , Khan Imran , Ahmadi Tahamtan , Nahi Hareth 
Published: May 2016

Key Points
A pooled analysis of 2 daratumumab trials showed no new safety signals, an overall response rate of 31%, and deep and durable responses. Median overall survival was 20.1 months; benefit was also shown in patients who achieved minimal response/stable disease.
Tailored message interventions versus typical messages for increasing participation in colorectal cancer screening among a non-adherent population: A randomized controlled trial
Authors: Hirai Kei , Ishikawa Yoshiki , Fukuyoshi Jun , Yonekura Akio , Harada Kazuhiro , Shibuya Daisuke , Yamamoto Seiichiro , Mizota Yuri , Hamashima Chisato , Saito Hiroshi 
Published: May 2016

Abstract
Background
The purpose of this study was to examine the effectiveness and cost-efficiency of a tailored message intervention compared with a non-tailored message intervention for increasing colorectal cancer (CRC) screening rates among a non-adherent population, in a community-based client reminder program.

Methods
After a baseline survey for psychological segmentation, 2140 eligible individuals were randomly assigned either to a group with a tailored matched-message condition (N = 356), a group with a non-tailored unmatched-message condition (N = 355), or to two control groups, one using a typical message with a professional design (N = 717) and one without a professional design (N = 712). The main outcome measure was attendance rates in a community-organized CRC screening program within five months of receiving a print reminder.

Results
There was a significant difference in fecal occult blood test (FOBT) attendance rates at follow-up assessments between the tailored matched-message condition (14.0 %) and the control (9.9 %; OR = 1.48, p = 0.026), while there was no significant difference between the unmatched-message condition (11.0 %) and the control (OR = 1.12, p = 0.558), and between the matched-message condition and the unmatched-message condition (OR = 1.32, p = 0.219). The cost of a one-person increase in FOBT screening was 3,740 JPY for the tailored matched-message condition, while it was 2,747 JPY for the control.

Conclusions
A tailored-message intervention for segmented individuals designed to increase CRC screening rates in a community-based client reminder program was significantly effective compared to a usual reminder, but not more effective than an unmatched message in a randomized controlled trial, and was not sufficiently effective to highlight its value from a cost perspective. Therefore, the tailored intervention including target segmentation needs to be improved for future implementation in a CRC screening program for a non-adherent population.

Trial registration
UMIN Clinical Trials Registry UMIN000004384. Date of Registration: March 2011.