bluuebunny/crossref_metadata_2025_split huggingface dataset:
Providing laying hens in group-housed enriched cages with access to barley silage reduces aggressive and feather-pecking behaviour
Authors: Johannson S.G. , Raginski C. , Schwean-Lardner K. , Classen H.L. 
Published: May 2016

Two trials were conducted to study the effect of feeding barley silage on the behaviour and performance of beak-trimmed laying hens. In each trial, 20 hens and 2 roosters were housed in each of eight group-housed enriched cages, with four cages provided a laying hen diet and four cages additionally given free access to barley silage. Egg production and quality, and hen behaviour were assessed throughout the trials (Trial One 20–30 weeks; Trial Two 19–28 weeks). Data were analysed using Proc Mixed of SAS 9.4 and differences were significant when P ≤ 0.05. Silage-fed hens consumed 41 (13.9 g DM) and 50 (13.5 g DM) grams of silage per hen per day in Trials One and Two, respectively, while consuming less layer diet. Birds fed silage spent less time expressing aggressive and feather-pecking behaviours and in nest boxes, and more time feeding than control birds. Egg production, egg quality, and bird weight were not affected by treatment; yolk colour was darker for the silage treatment. Feathering quality was improved in silage-fed birds compared to control birds. It was concluded that providing hens with access to barley silage can improve welfare indicators without negatively affecting the egg production and egg quality.
Correctness and Completeness of Logic Programs
Authors: Drabent Włodzimierz 
Published: May 2016

We discuss proving correctness and completeness of definite clause logic programs. We propose a method for proving completeness, while for proving correctness we employ a method that should be well known but is often neglected. Also, we show how to prove completeness and correctness in the presence of SLD-tree pruning, and point out that approximate specifications simplify specifications and proofs.
We compare the proof methods to declarative diagnosis (algorithmic debugging), showing that approximate specifications eliminate a major drawback of the latter. We argue that our proof methods reflect natural declarative thinking about programs, and that they can be used, formally or informally, in everyday programming.
Disrupting Hypoxia-Induced Bicarbonate Transport Acidifies Tumor Cells and Suppresses Tumor Growth
Authors: McIntyre Alan , Hulikova Alzbeta , Ledaki Ioanna , Snell Cameron , Singleton Dean , Steers Graham , Seden Peter , Jones Dylan , Bridges Esther , Wigfield Simon , Li Ji-Liang , Russell Angela , Swietach Pawel , Harris Adrian L. 
Published: May 2016

Abstract
Tumor hypoxia is associated clinically with therapeutic resistance and poor patient outcomes. One feature of tumor hypoxia is activated expression of carbonic anhydrase IX (CA9), a regulator of pH and tumor growth. In this study, we investigated the hypothesis that impeding the reuptake of bicarbonate produced extracellularly by CA9 could exacerbate the intracellular acidity produced by hypoxic conditions, perhaps compromising cell growth and viability as a result. In 8 of 10 cancer cell lines, we found that hypoxia induced the expression of at least one bicarbonate transporter. The most robust and frequent inductions were of the sodium-driven bicarbonate transporters SLC4A4 and SLC4A9, which rely upon both HIF1α and HIF2α activity for their expression. In cancer cell spheroids, SLC4A4 or SLC4A9 disruption by either genetic or pharmaceutical approaches acidified intracellular pH and reduced cell growth. Furthermore, treatment of spheroids with S0859, a small-molecule inhibitor of sodium-driven bicarbonate transporters, increased apoptosis in the cell lines tested. Finally, RNAi-mediated attenuation of SLC4A9 increased apoptosis in MDA-MB-231 breast cancer spheroids and dramatically reduced growth of MDA-MB-231 breast tumors or U87 gliomas in murine xenografts. Our findings suggest that disrupting pH homeostasis by blocking bicarbonate import might broadly relieve the common resistance of hypoxic tumors to anticancer therapy. Cancer Res; 76(13); 3744–55. ©2016 AACR.
MFG-E8 Drives Melanoma Growth by Stimulating Mesenchymal Stromal Cell–Induced Angiogenesis and M2 Polarization of Tumor-Associated Macrophages
Authors: Yamada Kazuya , Uchiyama Akihiko , Uehara Akihito , Perera Buddhini , Ogino Sachiko , Yokoyama Yoko , Takeuchi Yuko , Udey Mark C. , Ishikawa Osamu , Motegi Sei-ichiro 
Published: May 2016

Abstract
Secretion of the powerful angiogenic factor MFG-E8 by pericytes can bypass the therapeutic effects of anti-VEGF therapy, but the mechanisms by which MFG-E8 acts are not fully understood. In this study, we investigated how this factor acts to promote the growth of melanomas that express it. We found that mouse bone marrow–derived mesenchymal stromal cells (MSC) expressed a substantial amount of MFG-E8. To assess its expression from this cell type, we implanted melanoma cells and MSC derived from wild type (WT) or MFG-E8 deficient [knockout (KO)] into mice and monitored tumor growth. Tumor growth and M2 macrophages were each attenuated in subjects coimplanted with KO-MSC compared with WT-MSC. In both xenograft tumors and clinical specimens of melanoma, we found that MFG-E8 expression was heightened near blood vessels where MSC could be found. Through in vitro assays, we confirmed that WT-MSC–conditioned medium was more potent at inducing M2 macrophage polarization, compared with KO-MSC–conditioned medium. VEGF and ET-1 expression in KO-MSC was significantly lower than in WT-MSC, correlating in vivo with reduced tumor growth and numbers of pericytes and M2 macrophages within tumors. Overall, our results suggested that MFG-E8 acts at two levels, by increasing VEGF and ET-1 expression in MSC and by enhancing M2 polarization of macrophages, to increase tumor angiogenesis. Cancer Res; 76(14); 4283–92. ©2016 AACR.
Biased Expression of the FOXP3Δ3 Isoform in Aggressive Bladder Cancer Mediates Differentiation and Cisplatin Chemotherapy Resistance
Authors: Zhang Hanwei , Prado Kris , Zhang Kelvin X. , Peek Elizabeth M. , Lee Jane , Wang Xiaoyan , Huang Jiaoti , Li Gang , Pellegrini Matteo , Chin Arnold I. 
Published: May 2016

Abstract
Purpose: The transcriptional regulation mediating cancer cell differentiation into distinct molecular subtypes and modulating sensitivity to existing treatments is an enticing therapeutic target. Our objective was to characterize the ability of the forkhead/winged transcription factor FOXP3 to modulate the differentiation of bladder cancer.
Experimental Design: Expression of FOXP3 was analyzed by immunohistochemistry in a tumor microarray of 587 samples and overall survival in a subset of 187 patients following radical cystectomy. Functional assays were performed in SW780 and HT1376 cell lines in vitro and in vivo and gene expression profiling performed by RNA-Seq. Validation was undertaken using gene expression profiles of 131 patients from The Cancer Genome Atlas (TCGA) consortium in bladder cancer.
Results: FOXP3 expression correlates with bladder cancer stage and inversely with overall survival, with biased expression of the FOXP3Δ3 isoform. Functional assays of FOXP3Δ3 demonstrated resistance to chemotherapy in vitro, whereas subcutaneous xenografts overexpressing FOXP3Δ3 developed larger and more poorly differentiated bladder cancers. RNA expression profiling revealed a unique FOXP3Δ3 gene signature supporting a role in chemotherapy resistance. Accordingly, knockdown of Foxp3 by siRNA in HT1376 cells conferred sensitivity to cisplatin- and gemcitabine-induced cytotoxicity. Validation in TCGA dataset demonstrated increased expression of FOXP3 in subtypes II to IV and skewing of molecular subtypes based on FOXP3Δ3-specific gene expression.
Conclusions: (i) Biased expression of the FOXP3Δ3 isoform in bladder cancer inversely correlates with overall survival, (ii) FOXP3Δ3 induces a unique gene program that mediates cancer differentiation, and (iii) FOXP3Δ3 may augment chemotherapy resistance. Clin Cancer Res; 22(21); 5349–61. ©2016 AACR.
Characterization of CD33/CD3 Tetravalent Bispecific Tandem Diabodies (TandAbs) for the Treatment of Acute Myeloid Leukemia
Authors: Reusch Uwe , Harrington Kimberly H. , Gudgeon Chelsea J. , Fucek Ivica , Ellwanger Kristina , Weichel Michael , Knackmuss Stefan H.J. , Zhukovsky Eugene A. , Fox Judith A. , Kunkel Lori A. , Guenot Jeanmarie , Walter Roland B. 
Published: May 2016

Abstract
Purpose: Randomized studies with gemtuzumab ozogamicin have validated CD33 as a target for antigen-specific immunotherapy of acute myelogenous leukemia (AML). Here, we investigated the potential of CD33/CD3-directed tandem diabodies (TandAbs) as novel treatment approach for AML. These tetravalent bispecific antibodies provide two binding sites for each antigen to maintain the avidity of a bivalent antibody and have a molecular weight exceeding the renal clearance threshold, thus offering a longer half-life compared to smaller antibody constructs.
Experimental Design: We constructed a series of TandAbs composed of anti-CD33 and anti-CD3 variable domains of diverse binding affinities and profiled their functional properties in CD33+ human leukemia cell lines, xenograft models, and AML patient samples.
Results: Our studies demonstrated that several CD33/CD3 TandAbs could induce potent, dose-dependent cytolysis of CD33+ AML cell lines. This effect was modulated by the effector-to-target cell ratio and strictly required the presence of T cells. Activation and proliferation of T cells and maximal AML cell cytolysis correlated with high avidity to both CD33 and CD3. High-avidity TandAbs were broadly active in primary specimens from patients with newly diagnosed or relapsed/refractory AML in vitro, with cytotoxic properties independent of CD33 receptor density and cytogenetic risk. Tumor growth delay and inhibition were observed in both prophylactic and established HL-60 xenograft models in immunodeficient mice.
Conclusions: Our data show high efficacy of CD33/CD3 TandAbs in various preclinical models of human AML. Together, these findings support further study of CD33/CD3 TandAbs as novel immunotherapeutics for patients with AML. Clin Cancer Res; 22(23); 5829–38. ©2016 AACR.
Determination of Clinical Outcome in Mitral Regurgitation With Cardiovascular Magnetic Resonance Quantification
Authors: Myerson Saul G. , d’Arcy Joanna , Christiansen Jonathan P. , Dobson Laura E. , Mohiaddin Raad , Francis Jane M. , Prendergast Bernard , Greenwood John P. , Karamitsos Theodoros D. , Neubauer Stefan 
Published: May 2016

Background—
Surgery for severe mitral regurgitation is indicated if symptoms or left ventricular dilation or dysfunction occur. However, prognosis is already reduced by this stage, and earlier surgery on asymptomatic patients has been advocated if valve repair is likely, but identifying suitable patients for early surgery is difficult. Quantifying the regurgitation may help, but evidence for its link with outcome is limited. Cardiovascular magnetic resonance (CMR) can accurately quantify mitral regurgitation, and we examined whether this was associated with the future need for surgery.

Methods and Results—

One hundred nine asymptomatic patients with echocardiographic moderate or severe mitral regurgitation had baseline CMR scans and were followed up for up to 8 years (mean, 2.5±1.9 years). CMR quantification accurately identified patients who progressed to symptoms or other indications for surgery: 91% of subjects with regurgitant volume ≤55 mL survived to 5 years without surgery compared with only 21% with regurgitant volume >55 mL (
P
<0.0001). A similar separation was observed for regurgitant fraction ≤40% and >40%. CMR-derived end-diastolic volume index showed a weaker association with outcome (proportions surviving without surgery at 5 years, 90% for left ventricular end-diastolic volume index <100 mL/m
2
versus 48% for ≥100 mL/m
2
) and added little to the discriminatory power of regurgitant fraction/volume alone.

Conclusions—
CMR quantification of mitral regurgitation was associated with the development of symptoms or other indications for surgery and showed better discriminatory ability than the reference-standard CMR-derived ventricular volumes. CMR may be able to identify appropriate patients for early surgery, with the potential to change clinical practice, although the clinical benefits of early surgery require confirmation in a clinical trial.
ML-CIRRUS: The Airborne Experiment on Natural Cirrus and Contrail Cirrus with the High-Altitude Long-Range Research Aircraft HALO
Authors: Voigt Christiane , Schumann Ulrich , Minikin Andreas , Abdelmonem Ahmed , Afchine Armin , Borrmann Stephan , Boettcher Maxi , Buchholz Bernhard , Bugliaro Luca , Costa Anja , Curtius Joachim , Dollner Maximilian , Dörnbrack Andreas , Dreiling Volker , Ebert Volker , Ehrlich Andre , Fix Andreas , Forster Linda , Frank Fabian , Fütterer Daniel , Giez Andreas , Graf Kaspar , Grooß Jens-Uwe , Groß Silke , Heimerl Katharina , Heinold Bernd , Hüneke Tilman , Järvinen Emma , Jurkat Tina , Kaufmann Stefan , Kenntner Mareike , Klingebiel Marcus , Klimach Thomas , Kohl Rebecca , Krämer Martina , Krisna Trismono Candra , Luebke Anna , Mayer Bernhard , Mertes Stephan , Molleker Sergej , Petzold Andreas , Pfeilsticker Klaus , Port Max , Rapp Markus , Reutter Philipp , Rolf Christian , Rose Diana , Sauer Daniel , Schäfler Andreas , Schlage Romy , Schnaiter Martin , Schneider Johannes , Spelten Nicole , Spichtinger Peter , Stock Paul , Walser Adrian , Weigel Ralf , Weinzierl Bernadett , Wendisch Manfred , Werner Frank , Wernli Heini , Wirth Martin , Zahn Andreas , Ziereis Helmut , Zöger Martin 
Published: May 2016

Abstract
The Midlatitude Cirrus experiment (ML-CIRRUS) deployed the High Altitude and Long Range Research Aircraft (HALO) to obtain new insights into nucleation, life cycle, and climate impact of natural cirrus and aircraft-induced contrail cirrus. Direct observations of cirrus properties and their variability are still incomplete, currently limiting our understanding of the clouds’ impact on climate. Also, dynamical effects on clouds and feedbacks are not adequately represented in today’s weather prediction models.
Here, we present the rationale, objectives, and selected scientific highlights of ML-CIRRUS using the G-550 aircraft of the German atmospheric science community. The first combined in situ–remote sensing cloud mission with HALO united state-of-the-art cloud probes, a lidar and novel ice residual, aerosol, trace gas, and radiation instrumentation. The aircraft observations were accompanied by remote sensing from satellite and ground and by numerical simulations.
In spring 2014, HALO performed 16 flights above Europe with a focus on anthropogenic contrail cirrus and midlatitude cirrus induced by frontal systems including warm conveyor belts and other dynamical regimes (jet streams, mountain waves, and convection). Highlights from ML-CIRRUS include 1) new observations of microphysical and radiative cirrus properties and their variability in meteorological regimes typical for midlatitudes, 2) insights into occurrence of in situ–formed and lifted liquid-origin cirrus, 3) validation of cloud forecasts and satellite products, 4) assessment of contrail predictability, and 5) direct observations of contrail cirrus and their distinction from natural cirrus. Hence, ML-CIRRUS provides a comprehensive dataset on cirrus in the densely populated European midlatitudes with the scope to enhance our understanding of cirrus clouds and their role for climate and weather.
A Five-Century Reconstruction of Hawaiian Islands Winter Rainfall
Authors: Diaz Henry F. , Wahl Eugene R. , Zorita Eduardo , Giambelluca Thomas W. , Eischeid Jon K. 
Published: May 2016

Abstract
Few if any high-resolution (annually resolved) paleoclimate records are available for the Hawaiian Islands prior to ~1850 CE, after which some instrumental records start to become available. This paper shows how atmospheric teleconnection patterns between North America and the northeastern North Pacific (NNP) allow for reconstruction of Hawaiian Islands rainfall using remote proxy information from North America. Based on a newly available precipitation dataset for the state of Hawaii and observed and reconstructed December–February (DJF) sea level pressures (SLPs) in the North Pacific Ocean, the authors make use of a strong relationship between winter SLP variability in the northeast Pacific and corresponding DJF Hawaii rainfall variations to reconstruct and evaluate that season’s rainfall over the period 1500–2012 CE. A general drying trend, though with substantial decadal and longer-term variability, is evident, particularly during the last ~160 years. Hawaiian Islands rainfall exhibits strong modulation by El Niño–Southern Oscillation (ENSO), as well as in relation to Pacific decadal oscillation (PDO)-like variability. For significant periods of time, the reconstructed large-scale changes in the North Pacific SLP field described here and by construction the long-term decline in Hawaiian winter rainfall are broadly consistent with long-term changes in tropical Pacific sea surface temperature (SST) based on ENSO reconstructions documented in several other studies, particularly over the last two centuries. Also noted are some rather large multidecadal fluctuations in rainfall (and hence in NNP SLP) in the eighteenth century of undetermined provenance.
The Role of Reversed Equatorial Zonal Transport in Terminating an ENSO Event
Authors: Chen Han-Ching , Hu Zeng-Zhen , Huang Bohua , Sui Chung-Hsiung 
Published: May 2016

Abstract
This study shows the sudden basinwide reversal of anomalous equatorial zonal transport above the thermocline at the peaking phase of ENSO triggers rapid termination of ENSO events. The anomalous equatorial zonal transport is controlled by the concavity of anomalous thermocline meridional structure across the equator. During the developing phase of ENSO, opposite zonal transport anomalies form in the western-central and central-eastern equatorial Pacific, respectively. Both are driven by the equatorial thermocline anomalies in response to zonal wind anomalies over the western-central equatorial ocean. At this stage, the anomalous zonal transport in the east enhances ENSO growth through zonal SST advection. In the mature phase of ENSO, off-equatorial thermocline depth anomalies become more dominant in the eastern Pacific because of the reflection of equatorial signals at the eastern boundary. As a result, the meridional concavity of the thermocline anomalies is reversed in the east. This change reverses zonal transport rapidly in the central-to-eastern equatorial Pacific, joining with the existing reversed zonal transport anomalies farther to the west, and forms a basinwide transport reversal throughout the equatorial Pacific. This basinwide transport reversal weakens the ENSO SST anomalies by reversed advection. More importantly, the reversed zonal transport reduces the existing zonal tilting of the equatorial thermocline and weakens its feedback to wind anomalies effectively. This basinwide reversal is built in at the peak phase of ENSO as an oceanic control on the evolution of both El Niño and La Niña events. The reversed zonal transport anomaly after the mature phase weakens El Niño in the eastern Pacific more efficiently than it weakens La Niña.
A Multiscale Evaluation of the Detection Capabilities of High-Resolution Satellite Precipitation Products in West Africa
Authors: Guilloteau Clément , Roca Rémy , Gosset Marielle 
Published: May 2016

AbstractValidation studies have assessed the accuracy of satellite-based precipitation estimates at coarse scale (1° and 1 day or coarser) in the tropics, but little is known about their ability to capture the finescale variability of precipitation. Rain detection masks derived from four multisatellite passive sensor products [Tropical Amount of Precipitation with an Estimate of Errors (TAPEER), PERSIANN-CCS, CMORPH, and GSMaP] are evaluated against ground radar data in Burkina Faso. The multiscale evaluation is performed down to 2.8 km and 15 min through discrete wavelet transform. The comparison of wavelet coefficients allows identification of the scales for which the precipitation fraction (fraction of space and time that is rainy) derived from satellite observations is consistent with the reference. The wavelet-based spectral analysis indicates that the energy distribution associated with the rain/no rain variability throughout spatial and temporal scales in satellite products agrees well with radar-based precipitation fields. The wavelet coefficients characterizing very finescale variations (finer than 40 km and 2 h) of satellite and ground radar masks are poorly correlated. Coarse spatial and temporal scales are essentially responsible for the agreement between satellite and radar masks. Consequently, the spectral energy of the difference between the two masks is concentrated in fine scales. Satellite-derived multiyear mean diurnal cycles of rain occurrence are in good agreement with gauge data in Benin and Niger. Spectral analysis and diurnal cycle computation are also performed in the West Africa region using the TRMM Precipitation Radar. The results at the regional scale are consistent with the results obtained over the ground radar and gauge sites.
What Happens With Untreated Nasal Polyps Over Time? A 13-Year Prospective Study
Authors: Oscarsson Martin , Johansson Leif , Bende Mats 
Published: May 2016

Objectives: Nasal polyps are often seen in ENT practice, but little is known about the pathogenesis and the natural development. Our objective was to follow individuals with untreated nasal polyps prospectively, in terms of polyp size, symptoms, and respiratory function. Methods: Thirty-three individuals, aged 27 to 87 years, with untreated nasal polyps were identified in a population-based study. Peak nasal inspiratory flow, olfactory function, and size of the nasal polyps were examined. Respiratory symptoms were also registered. Follow-up examinations were performed after 6 and 13 years, with change between visits analyzed. Results: Over time, polyp size as well as occurrence of unilateral or bilateral polyps varied without an obvious pattern, with no consistent trends in respiratory function or symptoms. Twenty-one individuals (64%) were still untreated at the 6-year follow-up, and 12 (36%) remained untreated during the whole 13-year follow-up. Dropouts were due mainly to death. Seven individuals (21%) started treatment during the follow-up and had larger polyps and more subjective respiratory symptoms at baseline compared to the untreated group. Conclusion: Nasal polyps found occasionally are often part of a chronic entity but do not necessarily evolve into a more serious condition over time. Treatment should therefore be based on the patients’ subjective problems.