bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulatory and strategic considerations for addressing immunogenicity and related responses in biopharmaceutical development programs
Authors: Vandivort Tyler C. , Horton David B. , Johnson Steven B. 
Published: June 2020

AbstractThe last three decades have seen the biotherapeutic drug market evolve from promising concept to market dominance in a range of clinical indications. This growth has been spurred by the success of established drug classes like monoclonal antibodies, but also by the introduction of biosimilars, and more recently, multiple novel cell and gene therapies. Biotherapeutic drug development presents many unique challenges, but unintended immune responses are among the most common reasons for program attrition. Anti-drug antibodies can impact the safety and efficacy of drug products, and related immune responses, like the cytokine release syndrome that occurred in the infamous TGN-1412 clinical trial, can be challenging to predict with nonclinical models. For this reason, it is important that development programs proceed with a scientifically grounded and measured approach to these responses. This process begins at the discovery stage with the application of “quality by design,” continues into the clinic with the development of quality assays and management strategies, and culminates in the effective presentation of this information in regulatory documents. This review provides an overview of some of the key strategic and regulatory considerations for biotherapeutics as they pertain to immunogenicity and related responses.
Habermasian utopia or Sunstein's echo chamber? The ‘dark side’ of hashtag hijacking and feminist activism
Authors: Dempsey Willis Reilly Anne 
Published: June 2020

AbstractSociety thinks, talks, and communicates in ways which are inherently different now from the pre-Internet era. Hashtags in particular have transformed community formation around a particular topic, issue, or goal. A new and relatively under-studied phenomenon is that of ‘hashtag hijacking’, where individuals or groups use a particular hashtag to draw attention to arguments and narratives which undermine or oppose the hashtag's objective. Most of the current literature looks at hashtag hijacking as a positive outlet for counter-discourse/counter-narratives to challenge dominant groups. This study, however, looks at the ‘dark side’ of hashtag hijacking, where groups use trolling tactics similar to the Alt_Right to reinforce misogynistic views. The hijacking of three hashtags is explored in this study: #notacriminal, #women2drive, and #mydressmychoice, to explore feminist theories on the role of social media in a ‘public space’. Does Twitter function as one common public sphere where inequalities are so deeply embedded that minority voices have no hope of being heard? Or does Twitter function as a meeting place for multiple competing public spheres, thus allowing minority – and in this case feminist – voices to be heard?
Paleo-Critical Zones, windows into the changing life and landscapes during the Quaternary Period
Authors: Ashley Gail M. 
Published: June 2020

ABSTRACTThe Critical Zone (CZ) as visualized in 1998 was a way to integrate the research of the four scientific spheres (lithosphere, hydrosphere, biosphere and atmosphere) at the surface of Earth and to study the linkages, feedbacks and record of processes. Rather than closeting studies by a variety of disciplines into their respective pigeonholes the CZ perspective provides the symbiotic framework from which the tendrils of improved understanding can radiate outward to new disciplines and/or feedback into the component disciplines. During the last 2 decades, CZ research has been limited to the modern environment. Knowledge gained from the modern and the focus on interpreting ancient records allows for the development of paleo-CZs (PCZs). PCZs provide a powerful tool for improved understanding of the landscapes during the Quaternary Period and the response of this thin skin to glaciations, sea level fluctuations and evolving life. Case studies from hominins in East Africa andHomo sapiensin the Americas provide examples of the rich records stored in PCZs. As we move into the space age, the CZ can provide a platform from which to guide future exploration of the proto Critical Zones on the rocky planets and asteroids of our solar system.
Canada in the North America Region: Implications of the Trump Presidency
Authors: Macdonald Laura 
Published: June 2020

AbstractThe election of Donald Trump and his decision to renegotiate the North American Free Trade Agreement (NAFTA) represented a shock to the Canadian and Mexican governments and business elites. Drawing on the New Regionalism(s) Approach (NRA), this article reviews the response of the Canadian state to the crisis in the North American regional project. I argue that this newer theoretical approach better explains the dynamics of regionalization or regional decomposition than mainstream theories by integrating the role played by uneven globalization, normative and ideational dimensions, and civil society in processes of regional integration and/or decomposition.
Impact of temperature and growth phases on lipid composition and fatty acid profile of a thermophilic Bacillariophyta strain related to the genus Halamphora from north-eastern Tunisia
Authors: Bouzidi Nahla , Zili Fatma , García-Maroto Federico , López Alonso Diego , Ben Ouada Hatem 
Published: June 2020

AbstractA thermo-tolerant diatom species has been isolated from Tunisian hot spring water (40°C). The isolated diatom has been molecularly identified and classified into the genus Halamphora. The growth kinetics, lipid content and distribution of fatty acids were assessed at 20 and 30°C temperature levels and constant irradiance in controlled batch cultures (11 days). Halamphora sp. showed better growth (μ = 0.53 day−1) and a higher lipid yield (25% of the dry weight) at a higher temperature (30°C). Under the two temperatures tested, the highest lipid and fatty acid contents were mainly reached during the stationary growth phase. The fatty acid profile showed a significant content of two essential fatty acids, eicosapentaenoic acid (EPA, 20:5n-3) and arachidonic acid (AA, 20:4n-6), reaching ~15% and ~21% of the total fatty acids, respectively, at 20°C and 30°C. The distribution of the different components of the fatty acids showed that EPA and AA were mainly located in the neutral lipid fraction in the stationary phase.
Frontal EEG asymmetry moderates the associations between negative temperament and behavioral problems during childhood
Authors: Liu Ran , Calkins Susan D. , Bell Martha Ann 
Published: June 2020

AbstractFearful inhibition and impulsivity-anger significantly predict internalizing and externalizing problems, respectively. An important moderator that may affect these associations is frontal EEG asymmetry (FA). We examined how temperament and FA at 6 years interactively predicted behavioral problems at 9 years. A community sample of 186 children (93 boys, 93 girls) participated in the study. Results indicated that the effect of fearful inhibition on parent-reported internalizing problems increased as children exhibited greater right FA. The effect of impulsivity-anger on parent-reported externalizing problems increased as children showed greater left FA. Because FA was allowed to vary rather than children being dichotomized into membership in left FA and right FA groups, we observed that children’s FA contributed to the resilience process only when FA reached specific asymmetry levels. These findings highlight the importance of considering the different functions of FA in combination with specific dimensions of temperament in predicting children’s socioemotional outcomes. Clinical implications include providing suggestions for intervention services by demonstrating the role of FA in developing behavioral problems and inspiring research on whether it is possible to alter EEG activation and thus potentially improve developmental outcomes.
Nitrogen fertilizer programs following rice exposure to a sub-lethal concentration of paraquat
Authors: Lawrence Benjamin H. , Bond Jason A. , Golden Bobby R. , Allen Thomas W. , Reynolds Daniel B. , Bararpour Taghi 
Published: June 2020

AbstractOff-target paraquat movement to rice has become a major problem in recent years for rice producers in the midsouthern United States. Nitrogen (N) fertilizer is applied to rice in greater quantity and frequency than all other nutrients to optimize rice yield. Two separate field studies were conducted from 2015 to 2018 in Stoneville, MS, to assess whether starter N fertilizer can aid rice recovery from exposure to a sub-lethal concentration of paraquat and to evaluate rice response to different N fertilizer management strategies following exposure to a sub-lethal concentration of paraquat. In both studies, paraquat treatments consisted of paraquat at 0 and 84 g ai ha–1 applied to rice in the two- to three-leaf (EPOST) growth stage. In the starter fertilizer study, N fertilizer at 24 kg ha–1 as ammonium sulfate (AMS) was applied to rice at spiking- to one-leaf (VEPOST), two- to three-leaf (EPOST), or three- to four-leaf (MPOST) growth stages before and after paraquat treatment. In the N fertilizer timing study, N fertilizer at 168 kg N ha–1 was applied in a single four-leaf to one-tiller (LPOST) application or two-, three-, and two four-way split applications. Despite starter N fertilizer applications, paraquat injured rice ≥41%, reduced height 57%, reduced dry weight prior to flooding 77%, delayed maturity 10 d, reduced dry weight at maturity 33%, and reduced rough rice yield 35% in the starter fertilizer study. Similarly, in the N fertilizer timing study, paraquat injured rice ≥45%, reduced height 14%, delayed maturity 10 d, reduced dry weight at maturity 44%, and reduced rough rice yield 50% for all N fertilizer management strategies. Both studies indicate that severe complications in growth and development can occur from rice exposure to a sub-lethal concentration of paraquat. In both studies, manipulation of N fertilizer management did not facilitate rice recovery from early-season exposure to paraquat.
Radiogenic Power and Geoneutrino Luminosity of the Earth and Other Terrestrial Bodies Through Time
Authors: McDonough W. F. , Šrámek O. , Wipperfurth S. A. 
Published: June 2020

AbstractWe report the Earth's rate of radiogenic heat production and (anti)neutrino luminosity from geologically relevant short‐lived radionuclides (SLR) and long‐lived radionuclides (LLR) using decay constants from the geological community, updated nuclear physics parameters, and calculations of theβspectra. We track the time evolution of the radiogenic power and luminosity of the Earth over the last 4.57 billion years, assuming an absolute abundance for the refractory elements in the silicate Earth and key volatile/refractory element ratios (e.g., Fe/Al, K/U, and Rb/Sr) to set the abundance levels for the moderately volatile elements. The relevant decays for the present‐day heat production in the Earth (19.9 ± 3.0 TW) are from40K,87Rb,147Sm,232Th,235U, and238U. Given element concentrations in kg‐element/kg‐rock and densityρin kg/m3, a simplified equation to calculate the present‐day heat production in a rock isurn:x-wiley:ggge:media:ggge22244:ggge22244-math-0001The radiogenic heating rate of Earth‐like material at solar system formation was some 103to 104times greater than present‐day values, largely due to decay of26Al in the silicate fraction, which was the dominant radiogenic heat source for the first∼10 Ma. Assuming instantaneous Earth formation, the upper bound on radiogenic energy supplied by the most powerful short‐lived radionuclide26Al (t1/2= 0.7 Ma) is 5.5×1031 J, which is comparable (within a factor of a few) to the planet's gravitational binding energy.
Geomagnetic and Solar Dependency of MSTIDs Occurrence Rate: A Climatology Based on Airglow Observations From the Arecibo Observatory ROF
Authors: Terra Pedrina , Vargas Fabio , Brum Christiano G. M. , Miller Ethan S. 
Published: June 2020

AbstractWe employ in this work the first O(1D) 630.0‐nm airglow data set registered at the Remote Optical Facility (ROF) in Culebra, Puerto Rico, during the descending phase of the solar cycle #24. From 4 November 2015 to 26 September 2019, observations were carried out during 633 nights at ROF using a small all‐sky imager, while MSTID events were identified in 225 of 499 nights classified as clear. A quantitative analysis of these MSTIDs and their dependency by geophysical parameters (solar and geomagnetic activities) are the main focus of this study. We introduce an original statistical methodology that examines the unique features of the data set and minimizes the cross contamination of individual modulators onto one another, avoiding bias in the results. Our findings include a primary peak of MSTIDs occurrence in the December solstice and a secondary peak in the June solstice. We observed a remarkable correlation in the occurrence rate of the MSTIDs with the geomagnetic activity. A notable modulation of the MSTIDs occurrence rate with the solar activity is also found, which includes periods of correlation and anticorrelation depending on the season. This modulation has an annual component that is ~33% and ~83% stronger than the semiannual and terannual components, respectively. We discuss these findings based on a previous study of the thermospheric neutral winds derived from 30 years of Fabry‐Perot interferometer observations at Arecibo Observatory. Our results, which are valid for low to moderate solar activity, point out circumstances that might explain differences in previous climatological studies of nighttime MSTIDs.
How Sediment Thickness Influences Subduction Dynamics and Seismicity
Authors: Brizzi Silvia , van Zelst Iris , Funiciello Francesca , Corbi Fabio , van Dinther Ylona 
Published: June 2020

AbstractIt has long been recognized that sediments subducting along the megathrust influence the occurrence of giant (Mw ≥ 8.5) megathrust earthquakes. However, the limited observation span and the concurrent influence of multiple parameters on megathrust behavior prevent us from understanding how sediments affect earthquake size and frequency. Here, we address these limitations by using two‐dimensional, visco‐elasto‐plastic, seismo‐thermo‐mechanical numerical models to isolate how sediment thickness affects subduction geometry and seismicity. Our results show that increasing sediment thickness on the incoming plate results in a decrease of the slab dip, as the trench retreats due to the seaward growth of the sedimentary wedge that also unbends the slab. This decrease in megathrust dip results in a wider seismogenic zone, so that the maximum magnitude of megathrust earthquakes increases. Concurrently, the recurrence time of characteristic events increases and partial ruptures are introduced. The maximum magnitude estimated for subduction segments with the thickest sediment input (Makran, West‐Aegean, and Calabria) is distinctly higher than the instrumentally recorded magnitude. These segments may thus experience larger than as of yet observed earthquakes, albeit infrequently. Increasing sediment thickness also decreases megathrust normal stresses, as the seismogenic zone is more shallow and overlain by a lighter forearc structure. Thicker incoming plate sediments also favor more splay fault activity, whereas we observe more outer rise events for low sediment thickness. Finally, we demonstrate that modeling long‐term subduction dynamics and sediment subduction is crucial for understanding and quantifying megathrust seismicity and seismic potential of subduction zones.
Sources, Transformation, and Fate of Dissolved Organic Matter in the Gravel Bar of a Prealpine Stream
Authors: Boodoo Kyle S. , Fasching Christina , Battin Tom J. 
Published: June 2020

AbstractGravel bars (GBs) are hotspots of biogeochemical activity, likely impacting carbon dynamics in streams and rivers. However, it remains unclear how GBs process dissolved organic matter (DOM) received from stream water and groundwater. Here we investigate the spatial and temporal variability of DOM concentration and composition within a GB using DOM absorbance and fluorescence measurements. We found clear seasonal and diurnal patterns in DOM composition within the GB, indicating changing contributions of DOM sources and transformation processes. While DOM composition was characterized by more protein‐like DOM in summer, with increasing contributions of humic‐like DOM toward winter within the stream water and GB, groundwater DOM exhibited a strong aromatic and humic‐like character year‐round. DOM composition and concentration varied diurnally during autumn and winter within the GB and stream water, while seasonally higher groundwater inputs in summer likely muted the diurnal pattern, pointing to the importance of seasonal hydrological controls on DOM dynamics. Mixing model analysis showed GB DOM characteristics to differ from that predicted by stream water‐groundwater mixing within the GB, particularly in summer. Dissolved organic carbon concentration decreased along flow paths through the GB with increasing residence time, likely pointing to microbial uptake and/or adsorption to sediment surfaces within the GB, with concurrent clear shifts in DOM composition. While freshly produced and more humified DOM increased along GB flow paths, protein‐like fluorescence (C3) was removed, indicating the simultaneous production and removal of DOM. Together, our findings highlight the role of GBs in DOM removal and transformation, influenced by seasonal shifts in temperature and hydrodynamics.
Spatial and Temporal Heterogeneity Analysis of Water Conservation in Beijing‐Tianjin‐Hebei Urban Agglomeration Based on the Geodetector and Spatial Elastic Coefficient Trajectory Models
Authors: Chen Junhe , Wang Dongchuan , Li Guodong , Sun Zhichao , Wang Xiao , Zhang Xian , Zhang Wei 
Published: June 2020

AbstractTo regulate regional water resources, it is essential to identify the relationships among the elements that influence water conservation. Taking the Beijing‐Tianjin‐Hebei urban agglomeration as the study area, the authors applied a new method in combination with a geodetector model and spatial elastic coefficient trajectory model to reveal factors controlling water conservation and to identify relationships among the elements driving water conservation, in which the water conservation capacity and its spatial distribution were achieved using an Integrated Valuation of Ecosystem Services and Tradeoffs model. The authors selected precipitation, potential evapotranspiration, temperature, land use, maximum burial depth of soil, plant‐available water content, soil‐saturated hydraulic conductivity, percentage slope, gross domestic product, and population as the spatial driving factors, which measured the influence on the distribution of water conservation capacity on the whole region, plateaus, mountains, and plains, respectively. On the basis of previous research results, the authors selected precipitation, potential evapotranspiration, and land use as time‐driven factors. The results indicated that the strong water conservation capacity was reflected primarily in the Yanshan and Taihang Mountains and the eastern coastal areas. The water conservation capacity of the entire region, mountains, plateaus, and plains was affected mainly by the soil‐saturated hydraulic conductivity, plant‐available water content, precipitation, and precipitation, respectively. Each driving factor exhibited a clearly interactive influence on the spatial distribution of water conservation in terms of space and time.
Extent and Cessation of the Mid‐Cretaceous Hikurangi Plateau Underthrusting: Impact on Global Plate Tectonics and the Submarine Chatham Rise
Authors: Riefstahl Florian , Gohl Karsten , Davy Bryan , Barrett Rachel 
Published: June 2020

AbstractSubduction of oceanic plateaux are events that have occurred infrequently in Earth's history. Although rare, these events are thought to considerably influence regional tectonics and global plate motions. In the mid‐Cretaceous the oceanic Hikurangi Plateau collided with the formerly active East Gondwana margin: An event which falls into the same of a sudden change from subduction to extensional processes, including graben formation, development rift basin development, and exhumation of metamorphic core complexes in the Zealandia continent as well as a global‐scale plate reorganization event. In this study, we use recently acquired seismic refraction and gravity data along one profile across the submarine Chatham Rise, which represent a former accretionary wedge of the East Gondwana subduction zone. We demonstrate that the southward extent of the subducted Hikurangi Plateau in the lower crust beneath the submarine Chatham Rise along our profile is only ~150. This is ~150 km less than the previously suggested extent. Furthermore, we interpret that a slice of the subducted Phoenix Plate remains attached to the southern edge of the Hikurangi Plateau. We suggest that cessation of subduction in response to the Hikurangi Plateau jamming as well as the rollback and detachment of the Phoenix Plate slab played an important role in the changing tectonic forces across Zealandia in mid‐Cretaceous. Moreover, we suggest that the subduction cessation along the Hikurangi Plateau segment led to the fragmentation of the Gondwana subduction zone and Phoenix Plate, which significantly influenced and potentially prolonged the global mid‐Cretaceous plate reorganization event.
Insights to the neural response to food cues in class III compared with class I and II obese adults using a sample of endometrial cancer survivors seeking weight loss
Authors: Nock Nora L. , Jiang Huangqi , Borato Lauren , Alberts Jay , Dimitropoulos Anastasia 
Published: June 2020

Abstract
Background
The rates of severe or Class III obesity (BMI ≥ 40.0 kg/m2) and endometrial cancer (EC) incidence and mortality have been increasing significantly in the United States. Adults with severe obesity are more likely to die and women with severe obesity have a higher risk of EC development and mortality than those with Class I/II obesity (BMI: 30–<40 kg/m2). However, no prior studies have evaluated the neural response to food cues by obesity severity/class in adults with or without cancer.

Methods
We conducted a functional magnetic resonance imaging visual food cue task in 85 obese Stage I EC survivors who were seeking weight loss in a lifestyle intervention at baseline. We evaluated the neural response to high-calorie vs. non-food images after an overnight fast (fasted state) and after eating a standardized meal (fed state), and grouped patients by obesity class (Class I/II: n = 38; Class III: n = 47).

Results
In the fasted state, we found increased activation in several regions including the dorsolateral prefrontal cortex (DLPFC) in Class III and Class I/II patients (whole brain cluster corrected (WBCC), p < 0.05), which was significantly higher in Class III vs. Class I/II (p < 0.05). We found decreased activation in the insula in the fasted state, which was significantly lower in Class I/II vs. Class III (p = 0.03). In the fed state, we found increased activation in the DLPFC in Class III and Class I/II (WBCC, p < 0.05). The increased activation in cognitive control/inhibition regions (DLPFC) is consistent with the summative literature; however, the decreased activation in taste information processing regions (insula) was unexpected.

Conclusions
Our results provide novel insights on food cue response between different classes of obesity and highlight the importance of targeting the DLPFC in weight loss interventions, particularly in severely obese patients. Additional studies examining food-related neural circuitry between different classes of obesity are needed.