bluuebunny/crossref_metadata_2025_split huggingface dataset:
ERBB signaling attenuates proinflammatory activation of nonclassical monocytes
Authors: Ryzhov Sergey , Matafonov Anton , Galindo Cristi L. , Zhang Qinkun , Tran Truc-Linh , Lenihan Daniel J. , Lenneman Carrie Geisberg , Feoktistov Igor , Sawyer Douglas B. 
Published: February 2017

Immune activation in chronic systolic heart failure (HF) correlates with disease severity and prognosis. Recombinant neuregulin-1 (rNRG-1) is being developed as a possible therapy for HF, based on the activation of ERBB receptors in cardiac cells. Work in animal models of HF led us to hypothesize that there may be direct effects of NRG-1 on immune system activation and inflammation. We investigated the expression of ERBB receptors and the effect of rNRG-1 isoform glial growth factor 2 (GGF2) in subpopulations of peripheral blood mononuclear cells (PB MNCs) in subjects with HF. We found that human monocytes express both ERBB2 and ERBB3 receptors, with high interindividual variability among subjects. Monocyte surface ERBB3 and TNF-α mRNA expression were inversely correlated in subjects with HF but not in human subjects without HF. GGF2 activation of ERBB signaling ex vivo inhibited LPS-induced TNF-α production, specifically in the CD14lowCD16+population of monocytes in a phosphoinositide 3-kinase-dependent manner. GGF2 suppression of TNF-α correlated directly with the expression of ERBB3. In vivo, a single dose of intravenous GGF2 reduced TNF-α expression in PB MNCs of HF subjects participating in a phase I safety study of GGF2. These results support a role for ERBB3 signaling in the regulation of TNF-α production from CD14lowCD16+monocytes and a need for further investigation into the clinical significance of NRG-1/ERBB signaling as a modulator of immune system function.NEW & NOTEWORTHY This study identified a novel role of neuregulin-1 (NRG-1)/ERBB signaling in the control of proinflammatory activation of monocytes. These results further improve our fundamental understanding of cardioprotective effects of NRG-1 in patients with heart failure.
Equations for O2and CO2solubilities in saline and plasma: combining temperature and density dependences
Authors: Christmas Kevin M. , Bassingthwaighte James B. 
Published: February 2017

Solubilities of respiratory gasses in water, saline, and plasma decrease with rising temperatures and solute concentrations. Henry’s Law, C = α·P, states that the equilibrium concentration of a dissolved gas is solubility times partial pressure. Solubilities in the water of a solution depend on temperature and the content of other solutes. Blood temperatures may differ more than 20°C between skin and heart, and an erythrocyte will undergo that range as blood circulates. The concentrations of O2and CO2are the driving forces for diffusion, exchanges, and for reactions. We provide an equation for O2and CO2solubilities, α, that allows for continuous changes in temperature, T, and solution density, ρ, in dynamically changing states:[Formula: see text]This two-exponential expression with a density scalar γ, and a density exponent β, accounts for solubility changes due to density changes of an aqueous solution. It fits experimental data on solubilities in water, saline, and plasma over temperatures from 20 to 40°C, and for plasma densities, ρsolup to 1.020 g/ml with ~0.3% error. The amounts of additional bound O2(to Hb) and CO2(bicarbonate and carbamino) depend on the concentrations in the local water space and the reaction parameters. During exercise, solubility changes are large; both ρsoland T change rapidly with spatial position and with time. In exercise hemoconcentration plasma, ρsolexceeds 1.02, whereas T may range over 20°C. The six parameters for O2and the six for CO2are constants, so solubilities are calculable continuously as T and ρsolchange.NEW & NOTEWORTHY Solubilities for oxygen and carbon dioxide are dependent on the density of the solution, on temperature, and on the partial pressure. We provide a brief equation suitable for hand calculators or mathematical modeling, accounting for these factors over a wide range of temperatures and solution densities for use in rapidly changing conditions, such as extreme exercise or osmotic transients, with better than 0.5% accuracy.
Soluble IL6R Expressed by Myeloid Cells Reduces Tumor-Specific Th1 Differentiation and Drives Tumor Progression
Authors: Tsukamoto Hirotake , Fujieda Koji , Hirayama Masatoshi , Ikeda Tokunori , Yuno Akira , Matsumura Keiko , Fukuma Daiki , Araki Kimi , Mizuta Hiroshi , Nakayama Hideki , Senju Satoru , Nishimura Yasuharu 
Published: February 2017

AbstractIL6 produced by tumor cells promotes their survival, conferring a poor prognosis in patients with cancer. IL6 also contributes to immunosuppression of CD4+ T cell–mediated antitumor effects. In this study, we focused on the impact of IL6 trans-signaling mediated by soluble IL6 receptors (sIL6R) expressed in tumor-bearing hosts. Higher levels of sIL6R circulating in blood were observed in tumor-bearing mice, whereas the systemic increase of sIL6R was not prominent in tumor-bearing mice with myeloid cell–specific conditional deletion of IL6R even when tumor cells produced sIL6R. Abundant sIL6R was released by CD11b+ cells from tumor-bearing mice but not tumor-free mice. Notably, IL6-mediated defects in Th1 differentiation, T-cell helper activity for tumor-specific CD8+ T cells, and downstream antitumor effects were rescued by myeloid-specific deletion of sIL6R. Expression of the T-cell transcription factor c-Maf was upregulated in CD4+ T cells primed in tumor-bearing mice in an IL6-dependent manner. Investigations with c-Maf loss-of-function T cells revealed that c-Maf activity was responsible for IL6/sIL6R-induced Th1 suppression and defective T-cell–mediated antitumor responses. In patients with cancer, myeloid cell–derived sIL6R was also possibly associated with Th1 suppression and c-Maf expression. Our results argued that increased expression of sIL6R from myeloid cells and subsequent c-Maf induction were adverse events for counteracting tumor-specific Th1 generation. Overall, this work provides a mechanistic rationale for sIL6R targeting to improve the efficacy of T-cell–mediated cancer immunotherapy. Cancer Res; 77(9); 2279–91. ©2017 AACR.
The Global Aerosol Synthesis and Science Project (GASSP): Measurements and Modeling to Reduce Uncertainty
Authors: Reddington C. L. , Carslaw K. S. , Stier P. , Schutgens N. , Coe H. , Liu D. , Allan J. , Browse J. , Pringle K. J. , Lee L. A. , Yoshioka M. , Johnson J. S. , Regayre L. A. , Spracklen D. V. , Mann G. W. , Clarke A. , Hermann M. , Henning S. , Wex H. , Kristensen T. B. , Leaitch W. R. , Pöschl U. , Rose D. , Andreae M. O. , Schmale J. , Kondo Y. , Oshima N. , Schwarz J. P. , Nenes A. , Anderson B. , Roberts G. C. , Snider J. R. , Leck C. , Quinn P. K. , Chi X. , Ding A. , Jimenez J. L. , Zhang Q. 
Published: February 2017

AbstractThe largest uncertainty in the historical radiative forcing of climate is caused by changes in aerosol particles due to anthropogenic activity. Sophisticated aerosol microphysics processes have been included in many climate models in an effort to reduce the uncertainty. However, the models are very challenging to evaluate and constrain because they require extensive in situ measurements of the particle size distribution, number concentration, and chemical composition that are not available from global satellite observations. The Global Aerosol Synthesis and Science Project (GASSP) aims to improve the robustness of global aerosol models by combining new methodologies for quantifying model uncertainty, to create an extensive global dataset of aerosol in situ microphysical and chemical measurements, and to develop new ways to assess the uncertainty associated with comparing sparse point measurements with low-resolution models. GASSP has assembled over 45,000 hours of measurements from ships and aircraft as well as data from over 350 ground stations. The measurements have been harmonized into a standardized format that is easily used by modelers and nonspecialist users. Available measurements are extensive, but they are biased to polluted regions of the Northern Hemisphere, leaving large pristine regions and many continental areas poorly sampled. The aerosol radiative forcing uncertainty can be reduced using a rigorous model–data synthesis approach. Nevertheless, our research highlights significant remaining challenges because of the difficulty of constraining many interwoven model uncertainties simultaneously. Although the physical realism of global aerosol models still needs to be improved, the uncertainty in aerosol radiative forcing will be reduced most effectively by systematically and rigorously constraining the models using extensive syntheses of measurements.
The Convection, Aerosol, and Synoptic-Effects in the Tropics (CAST) Experiment: Building an Understanding of Multiscale Impacts on Caribbean Weather via Field Campaigns
Authors: Hosannah N. , González J. , Rodriguez-Solis R. , Parsiani H. , Moshary F. , Aponte L. , Armstrong R. , Harmsen E. , Ramamurthy P. , Angeles M. , León L. , Ramírez N. , Niyogi D. , Bornstein B. 
Published: February 2017

Abstract
Modulated by global-, continental-, regional-, and local-scale processes, convective precipitation in coastal tropical regions is paramount in maintaining the ecological balance and socioeconomic health within them. The western coast of the Caribbean island of Puerto Rico is ideal for observing local convective dynamics as interactions between complex processes involving orography, surface heating, land cover, and sea-breeze–trade wind convergence influence different rainfall climatologies across the island. A multiseason observational effort entitled the Convection, Aerosol, and Synoptic-Effects in the Tropics (CAST) experiment was undertaken using Puerto Rico as a test case, to improve the understanding of island-scale processes and their effects on precipitation. Puerto Rico has a wide network of observational instruments, including ground weather stations, soil moisture sensors, a Next Generation Weather Radar (NEXRAD), twice-daily radiosonde launches, and Aerosol Robotic Network (AERONET) sunphotometers. To achieve the goals of CAST, researchers from multiple institutions supplemented existing observational networks with additional radiosonde launches, three high-resolution radars, continuous ceilometer monitoring, and air sampling in western Puerto Rico to monitor convective precipitation events. Observations during three CAST measurement phases (22 June–10 July 2015, 6–22 February 2016, and 24 April–7 May 2016) captured the most extreme drought in recent history (summer 2015), in addition to anomalously wet early rainfall and dry-season (2016) phases. This short article presents an overview of CAST along with selected campaign data.
Measuring Memory and Attention to Preview in Motion
Authors: Jagacinski Richard J. , Hammond Gordon M. , Rizzi Emanuele 
Published: February 2017

Objective Use perceptual-motor responses to perturbations to reveal the spatio-temporal detail of memory for the recent past and attention to preview when participants track a winding roadway. Background Memory of the recently passed roadway can be inferred from feedback control models of the participants’ manual movement patterns. Similarly, attention to preview of the upcoming roadway can be inferred from feedforward control models of manual movement patterns. Method Perturbation techniques were used to measure these memory and attention functions. Results In a laboratory tracking task, the bandwidth of lateral roadway deviations was found to primarily influence memory for the past roadway rather than attention to preview. A secondary auditory/verbal/vocal memory task resulted in higher velocity error and acceleration error in the tracking task but did not affect attention to preview. Attention to preview was affected by the frequency pattern of sinusoidal perturbations of the roadway. Conclusion Perturbation techniques permit measurement of the spatio-temporal span of memory and attention to preview that affect tracking a winding roadway. They also provide new ways to explore goal-directed forgetting and spatially distributed attention in the context of movement. More generally, these techniques provide sensitive measures of individual differences in cognitive aspects of action. Application Models of driving behavior and assessment of driving skill may benefit from more detailed spatio-temporal measurement of attention to preview.
Insight in psychosis: Standards, science, ethics and value judgment
Authors: Jacob KS 
Published: February 2017

Background: The clinical assessment of insight solely employs biomedical perspectives and criteria to the complete exclusion of context and culture and to the disregard of values and value judgments. Aim: The aim of this discussion article is to examine recent research from India on insight and explanatory models in psychosis and re-examine the framework of assessment, diagnosis and management of insight and explanatory models. Methods: Recent research from India on insight in psychosis and explanatory models is reviewed. Results: Recent research, which has used longitudinal data and adjusted for pretreatment variables, suggests that insight and explanatory models of illness at baseline do not predict course, outcome and treatment response in schizophrenia, which seem to be dependent on the severity and quality of the psychosis. It supports the view that people with psychosis simultaneously hold multiple and contradictory explanatory models of illness, which change over time and with the trajectory of the illness. It suggests that insight, like all explanatory models, is a narrative of the person’s reality and a coping strategy to handle with the varied impact of the illness. Conclusion: This article argues that the assessment of insight necessarily involves value entailments, commitments and consequences. It supports a need for a broad-based approach to assess awareness, attribution and action related to mental illness and to acknowledge the role of values and value judgment in the evaluation of insight in psychosis.
‘Powerlessness’ or ‘doing the right thing’ – Moral distress among nursing home staff caring for residents at the end of life: An interpretive descriptive study
Authors: Young Amanda , Froggatt Katherine , Brearley Sarah G 
Published: February 2017

Background: Caring for dying people can contribute to moral distress experienced by healthcare professionals. Moral distress can occur when this caring is restricted by organisational processes, resources or the provision of futile care. These factors apply to end of life care in nursing homes but research is lacking. Aim: To describe how nursing home staff experience moral distress when caring for residents during and at the end of life. Methods: An interpretive descriptive design, using the critical incident technique in semi-structured interviews to collect data from nursing home staff. Data were analysed using a thematic analysis approach. Setting: Four nursing homes in one large metropolitan area. Participants: A total of 16 staff: 2 nurse managers, 4 nurses and 10 care assistants. Findings: Participants described holding ‘good dying’ values which influenced their practice. The four practice-orientated themes of advocating, caring, communicating and relating with residents were found to influence interactions with residents, relatives, general practitioners, and colleagues. These led staff to be able to ‘do the right thing’ or to experience ‘powerlessness’, which could in turn lead to staff perceiving a ‘bad death’ for residents. Conclusion: When there are incongruent values concerning care between staff and others involved in the care of residents, staff feel powerless to ‘do the right thing’ and unable to influence care decisions in order to avoid a ‘bad death’. This powerlessness is the nature of their moral distress.
Halting natural resource depletion: Engaging with economic and political power
Authors: Lindenmayer David 
Published: February 2017

AbstractGlobally, fisheries and forestry have been characterised by substantial ecological and economic problems. Both sectors have become notorious for depleting the stocks on which they depend, eroding the value of harvested natural resources over time and having significant negative ‘by-catch’ impacts on non-target natural resources. Problems of resource overuse and potential ecosystem collapse inherently derive from poor decisions influenced by those with undue or excessive economic, political and labour market power. Solutions to problems of unsustainability of resource management will need to engage with these economic drivers and beneficiaries, and require strategies including better and more independent assessments of the status and condition of resources. Deep-seated problems caused by resource over-commitment need more robust approaches to resource assessment that (1) better account for uncertainty (including uncertainty resulting from stock losses due to disturbance), (2) avoid ratchet effects and (3) provide appropriate ecological parameters for resource harvest. The United Nations framework for environmental and economic accounting methods can help assess the economic and other contributions of different resource-based industries and inform decisions about trade-offs between competing interests. Finally, there is value in examining successful and unsuccessful industry restructuring, in which decisions to transition away from demonstrably unsustainable resource industries have been made.
The relational responsibilities of scientists: (Re) considering science as a practice
Authors: Bezuidenhout Louise 
Published: February 2017

Studies of science are increasingly drawing attention to the highly communal nature of research. Ethics, sociology, philosophy, and anthropology of science all emphasize the key role that collaborative actions play in the generation of scientific knowledge. Nonetheless, despite the increasing interest in these communal aspects of scientific research, studies on the relationships underpinning communality are commonly focused on the how the individual interacts with their peers and contributes to the epistemic activities of science. In contrast, there is little literature that broadens out the scope of this analysis to consider the multidimensional nature of these research relationships. In particular, little is said about how scientists mediate their social interactions with peers during daily laboratory research. Less, indeed, is said about the tradition of ‘learning through example’ that characterizes most in situ laboratory training. All of these relational activities are of critical importance in sustaining and perpetuating the practice of science. It therefore becomes important to ask how we understand these relational activities directed towards building and sustaining relationships in different loci for the primary purpose of strengthening the practice of research and sustaining the traditions of scientific research. Moreover, it is vital to consider how discussions on responsibility may be cached out for individual scientists. This article employs a virtue ethics approach to consider these issues. It begins by sketching out the plethora of different relationships present in daily laboratory practice using existing ethnographic studies. It then uses virtue ethics to identify specific responsibilities that individual scientists have in cultivating and safeguarding the development of these relationships. It concludes by suggesting ways in which these issues may be taken up in teaching responsible conduct to scientists.
Complement activation products in acute heart failure: Potential role in pathophysiology, responses to treatment and impacts on long-term survival
Authors: Trendelenburg Marten , Stallone Fabio , Pershyna Kateryna , Eisenhut Timo , Twerenbold Raphael , Wildi Karin , Dubler Denise , Schirmbeck Lucia , Puelacher Christian , Rubini Gimenez Maria , Sabti Zaid , Osswald Luca , Breidthardt Tobias , Müller Christian 
Published: February 2017

Background: Previous studies have indicated a correlation between heart failure, inflammation and poorer outcome. However, the pathogenesis and role of inflammation in acute heart failure (AHF) is incompletely studied and understood. The aim of our study was to explore the potential role of innate immunity – quantified by complement activation products (CAPs) – in pathophysiology, responses to treatment and impacts on long-term survival in AHF. Methods: In a prospective study enrolling 179 unselected patients with AHF, plasma concentrations of C4d, C3a and sC5b-9 were measured in a blinded fashion on the first day of hospitalisation and prior to discharge. The final diagnosis, including the AHF phenotype, was adjudicated by two independent cardiologists. Long-term follow-up was obtained. Findings in AHF were compared to that obtained in 75 healthy blood donors (control group). Results: Overall, concentrations of all three CAPs were significantly higher in patients with AHF than in healthy controls (all p < 0.001). In an age-adjusted subgroup analysis, significant differences could be confirmed for concentrations of C4d and sC5b-9, and these parameters further increased after 6 days of in-hospital treatment ( p < 0.001). In contrast, C3a levels in AHF patients did not differ from those of the control group in the age-adjusted subgroup analysis and remained constant during hospitalisation. Concentrations of C4d, C3a and sC5b-9 were significantly higher when AHF was triggered by an infection as compared to other triggers ( p < 0.001). In addition, CAP levels significantly correlated with each other ( r = 0.64–0.76), but did not predict death within 2 years. Conclusions: Activation of complement with increased plasma levels of C4d and sC5b-9 at admission and increasing levels during AHF treatment seems to be associated with AHF, particularly when AHF was triggered by an infection. However, CAPs do not have a prognostic value in AHF.