bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defining candidate mRNA and protein EV biomarkers to discriminate ccRCC and pRCC from non-malignant renal cells in vitro
Authors: Zieren Richard C. , Dong Liang , Clark David J. , Kuczler Morgan D. , Horie Kengo , Moreno Leandro Ferreira , Lih Tung-Shing M. , Schnaubelt Michael , Vermeulen Louis , Zhang Hui , de Reijke Theo M. , Pienta Kenneth J. , Amend Sarah R. 
Published: July 2021

AbstractRenal cell carcinoma (RCC) accounts for over 400,000 new cases and 175,000 deaths annually. Diagnostic RCC biomarkers may prevent overtreatment in patients with early disease. Extracellular vesicles (EVs) are a promising source of RCC biomarkers because EVs carry proteins and messenger RNA (mRNA) among other biomolecules. We aimed to identify biomarkers and assess biological functions of EV cargo from clear cell RCC (ccRCC), papillary RCC (pRCC), and benign kidney cell lines. EVs were enriched from conditioned cell media by size exclusion chromatography. The EV proteome was assessed using Tandem Mass Tag mass spectrometry (TMT-MS) and NanoString nCounter technology was used to profile 770 cancer-related mRNA present in EVs. The heterogeneity of protein and mRNA abundance and identification highlighted the heterogeneity of EV cargo, even between cell lines of a similar pathological group (e.g., ccRCC or pRCC). Overall, 1726 proteins were quantified across all EV samples, including 181 proteins that were detected in all samples. In the targeted profiling of mRNA by NanoString, 461 mRNAs were detected in EVs from at least one cell line, including 159 that were present in EVs from all cell lines. In addition to a shared EV cargo signature, pRCC, ccRCC, and/or benign renal cell lines also showed unique signatures. Using this multi-omics approach, we identified 34 protein candidate pRCC EV biomarkers and 20 protein and 8 mRNA candidate ccRCC EV biomarkers for clinical validation.
Submicron particle docetaxel intratumoral injection in combination with anti-mCTLA-4 into 4T1-Luc orthotopic implants reduces primary tumor and metastatic pulmonary lesions
Authors: Maulhardt Holly , Marin Alyson , Hesseltine Holly , diZerega Gere 
Published: July 2021

AbstractWe describe here characterization of the response of local and metastatic disease and immunomodulation following intratumoral (IT) injection of submicron particle docetaxel (SPD) administered alone or in combination with systemic antibody anti-mCTLA-4 (anti-mCTLA-4) in the metastatic 4T1-Luc2-1A4 (4T1) murine breast cancer model. In-life assessments of treatment tolerance, tumor volume (TV), and metastasis were performed (n = 10 animals/group). At study end, immune cell populations in tumor-site tissues and peripheral blood were analyzed using flow cytometry. Signs of distress typical of this aggressive tumor model occurred across all animals except for the combination treated which were asymptomatic and gained weight. TV at study end was significantly reduced in the combination group versus untreated [43% reduced (p < 0.05)] and vehicle controls [54% reduced (p < 0.0001)]. No evidence of thoracic metastasis was found in 40% of combination group animals and thoracic bioluminescence imaging (BLI) was reduced vs. untreated controls (p < 0.01). Significant elevations (p < 0.05) in CD4 + T, CD4 + helper T, Treg, and NKT cells were found in tumor and blood in SPD or combination treatment compared to controls or anti-mCTLA-4. Combination treatment increased tumor-associated CD8 + T cells (p < 0.01), peripheral B cells (p < 0.01), and tumor associated and circulating dendritic cells (DC) (p < 0.05). Tumor-associated NK cells were significantly increased in SPD ± anti-mCTLA-4 treatments (p < 0.01). Myeloid-derived suppressor cells (MDSC) were reduced in bloods in SPD ± anti-mCTLA-4 groups (p < 0.05). These data demonstrate that both SPD and anti-mCTLA-4 produce local anti-tumor effects as well as reductions in metastasis which are significantly enhanced when administered in combination.
Spared Nerve Injury Causes Sexually Dimorphic Mechanical Allodynia and Differential Gene Expression in Spinal Cords and Dorsal Root Ganglia in Rats
Authors: Ahlström F.H.G. , Mätlik K. , Viisanen H. , Blomqvist K.J. , Liu X. , Lilius T.O. , Sidorova Y. , Kalso E.A. , Rauhala P.V. 
Published: July 2021

AbstractNeuropathic pain is more prevalent in women. However, females are under-represented in animal experiments, and the mechanisms of sex differences remain inadequately understood. We used the spared nerve injury (SNI) model in rats to characterize sex differences in pain behaviour, unbiased RNA-Seq and proteomics to study the mechanisms. Male and female rats were subjected to SNI- and sham-surgery. Mechanical and cold allodynia were assessed. Ipsilateral lumbar dorsal root ganglia (DRG) and spinal cord (SC) segments were collected for RNA-seq analysis with DESeq2 on Day 7. Cerebrospinal fluid (CSF) samples for proteomic analysis and DRGs and SCs for analysis of IB-4 and CGRP, and IBA1 and GFAP, respectively, were collected on Day 21. Females developed stronger mechanical allodynia. There were no differences between the sexes in CGRP and IB-4 in the DRG or glial cell markers in the SC. No CSF protein showed change following SNI. DRG and SC showed abundant changes in gene expression. Sexually dimorphic responses were found in genes related to T-cells (cd28, ctla4, cd274, cd4, prf1), other immunological responses (dpp4, c5a, cxcr2 and il1b), neuronal transmission (hrh3, thbs4, chrna4 and pdyn), plasticity (atf3, c1qc and reg3b), and others (bhlhe22, mcpt1l, trpv6). We observed significantly stronger mechanical allodynia in females and numerous sexually dimorphic changes in gene expression following SNI in rats. Several genes have previously been linked to NP, while some are novel. Our results suggest gene targets for further studies in the development of new, possibly sex-specific, therapies for NP.
Functional and Anatomical Characterization of Corticotropin-Releasing Factor Receptor Subtypes of the Rat Spinal Cord Involved in Somatic Pain Relief
Authors: Mousa Shaaban A. , Shaqura Mohammed , Khalefa Baled I. , Li Li , Al-Madol Mohammed , Treskatsch Sascha , Schäfer Michael 
Published: July 2021

AbstractCorticotropin-releasing factor (CRF) orchestrates our body’s response to stressful stimuli. Pain is often stressful and counterbalanced by activation of CRF receptors along the nociceptive pathway, although the involvement of the CRF receptor subtypes 1 and/or 2 (CRF-R1 and CRF-R2, respectively) in CRF-induced analgesia remains controversial. Thus, the aim of the present study was to examine CRF-R1 and CRF-R2 expression within the spinal cord of rats with Freund’s complete adjuvant-induced unilateral inflammation of the hind paw using reverse transcriptase polymerase chain reaction, Western blot, radioligand binding, and immunofluorescence confocal analysis. Moreover, the antinociceptive effects of intrathecal (i.t.) CRF were measured by paw pressure algesiometer and their possible antagonism by selective antagonists for CRF-R1 and/or CRF-R2 as well as for opioid receptors. Our results demonstrated a preference for the expression of CRF-R2 over CRF-R1 mRNA, protein, binding sites and immunoreactivity in the dorsal horn of the rat spinal cord. Consistently, CRF as well as CRF-R2 agonists elicited potent dose-dependent antinociceptive effects which were antagonized by the i.t. CRF-R2 selective antagonist K41498, but not by the CRF-R1 selective antagonist NBI35965. In addition, i.t. applied opioid antagonist naloxone dose-dependently abolished the i.t. CRF- as well as CRF-R2 agonist-elicited inhibition of somatic pain. Importantly, double immunofluorescence confocal microscopy of the spinal dorsal horn showed CRF-R2 on enkephalin (ENK)-containing inhibitory interneurons in close opposition of incoming mu-opioid receptor-immunoreactive nociceptive neurons. CRF-R2 was, however, not seen on pre- or on postsynaptic sensory neurons of the spinal cord. Taken together, these findings suggest that i.t. CRF or CRF-R2 agonists inhibit somatic inflammatory pain predominantly through CRF-R2 receptors located on spinal enkephalinergic inhibitory interneurons which finally results in endogenous opioid-mediated pain inhibition.
Effects of water salinity on the foam dynamics for EOR application
Authors: Rudyk Svetlana , Al-Khamisi Sami , Al-Wahaibi Yahya 
Published: July 2021

AbstractFactors limiting foam injection for EOR application are exceptionally low rock permeability and exceedingly high salinity of the formation water. In this regard, foam formation using internal olefin sulfonate is investigated over a wide salinity range (1, 5, 8, 10, and 12% NaCl) through 10 mD limestone. The relationships between pressure drop (dP), apparent viscosity, liquid flow rate, total flow rate, salinity, foam texture, and length of foam drops at the outlet used as an indicator of viscosity are studied. Foaming is observed up to 12% NaCl, compared to a maximum of 8% NaCl in similar core-flooding experiments with 50 mD limestone and 255 mD sandstone. Thus, the salinity limit of foam formation has increased significantly due to the low permeability, which can be explained by the fact that the narrow porous system acts like a membrane with smaller holes. Compared to the increasing dP reported for highly permeable rocks, dP linearly decreases in almost the entire range of gas fraction (fg) at 1–10% NaCl. As fg increases, dP at higher total flow rate is higher at all salinities, but the magnitude of dP controls the dependence of apparent viscosity on total flow rate. Low dP is measured at 1% and 10% NaCl, and high dP is measured at 5, 8, and 12% NaCl. In the case of low dP, the apparent viscosity is higher at higher total flow rate with increasing gas fraction, but similar at two total flow rates with increasing liquid flow rate. In the case of high dP, the apparent viscosity is higher at lower total flow rate, both with an increase in the gas fraction and with an increase in the liquid flow rate. A linear correlation is found between dP or apparent viscosity and liquid flow rate, which defines it as a governing factor of foam flow and can be considered when modeling foam flow.
Designing a unique feedback mechanism for hydrogel-forming microneedle array patches: a concept study
Authors: Hutton Aaron R. J. , Kirkby Melissa , Larrañeta Eneko , Donnelly Ryan F. 
Published: July 2021

AbstractAlthough microneedle array patch (MAP) technology is reaching ever closer to regulatory approval, it remains imperative that approaches to further improve patient acceptance are still explored. Addressing this perception, a water-filled reservoir was incorporated into a hydrogel-forming MAP system to provide a novel feedback mechanism. To confirm successful MAP skin insertion, the end user would both hear and feel the rupture of the water-filled reservoir. Interestingly, a 50-µL water-filled reservoir ruptured at 30.27 ± 0.39 N, which has previously been shown as the mean application force for MN insertion in human subjects following appropriate instruction. Importantly, no significant difference in % cumulative permeation of FITC-dextran 10 kDa and fluorescein sodium after 24 h was observed between a 50-µL reservoir and the current method of application that has been successfully used in both in vitro and in vivo studies (p > 0.05). Therefore, as drug delivery was not affected, this proof-of-concept study has shown that a water-filled reservoir feedback mechanism has the potential to serve as a viable tool for consistent MAP skin insertion.
Graphical abstract
Feasibility of hydrogen fuel cell technology for railway intercity services: a case study for the Piedmont in North Carolina
Authors: Madovi Orwell , Hoffrichter Andreas , Little Nick , Foster Shanelle N. , Isaac Raphael 
Published: July 2021

AbstractDiesel fuel combustion results in exhaust containing air pollutants and greenhouse gas emissions. Many railway vehicles use diesel fuel as their energy source. Exhaust emissions, as well as concerns about economical, alternative power supply, have driven efforts to move to hydrogen motive power. Hydrogen fuel cell technology applied to railways offers the opportunity to eliminate harmful exhaust emissions and the potential for a low- or zero-emission energy supply chain. Currently, only multiple-unit trains with hydrail technology operate commercially. Development of an Integrated Hybrid Train Simulator for intercity railway is presented. The proposed tool incorporates the effect of powertrain components during the wheel-to-tank process. Compared to its predecessors, the proposed reconfigurable tool provides high fidelity with medium requirements and minimum computation time. Single train simulation and the federal government’s Greenhouse gases, Regulated Emissions, and Energy use in Transportation (GREET®) model are used in combination to evaluate the feasibility of various train and powertrain configurations. The Piedmont intercity service operating in North Carolina is used as a case study. The study includes six train configurations and powertrain options as well as nine hydrogen supply options in addition to the diesel supply. The results show that a hydrail option is not only feasible, but a low- or zero-carbon hydrogen supply chain could be possible.
Bio-inspired smart surface to achieve controllable locomotion through adjustable anisotropic friction
Authors: Ji Zhongying , Qin Shiyu , Ma Shuanhong , Jia Xin , Wang Xiaolong , Zhou Feng 
Published: July 2021

AbstractAnisotropic friction generated by microstructured surfaces is crucial for performing functions such as directional locomotion and adhesion in biological systems. Hence, an epoxy-based shape memory polymer (SMP) incorporating Fe3O4 nanoparticles is used in this study to create a smart surface with oriented structures to mimic anisotropic friction and exploit human-developed controllable locomotion systems. Applying the specific properties of the epoxy-based SMP, fast switching friction can be achieved by adjusting the topography and stiffness of the microstructures on the surface. In addition, the photothermogenesis effect of Fe3O4 nanoparticles induces changes in the asymmetric topography and stiffness on the SMP surface under the irradiation of near-infrared (NIR) light, thereby inducing a rapid switching of the friction force. Furthermore, a microbot is created to demonstrate remotely controlled locomotion, such as unidirectional and round-trip movements, and braking by switching the friction force under NIR light. These results are promising for the design of new intelligent surfaces and interfaces; additionally, they may facilitate the investigation of biological structures and processes.
Learning quantized neural nets by coarse gradient method for nonlinear classification
Authors: Long Ziang , Yin Penghang , Xin Jack 
Published: July 2021

AbstractQuantized or low-bit neural networks are attractive due to their inference efficiency. However, training deep neural networks with quantized activations involves minimizing a discontinuous and piecewise constant loss function. Such a loss function has zero gradient almost everywhere (a.e.), which makes the conventional gradient-based algorithms inapplicable. To this end, we study a novel class of biased first-order oracle, termed coarse gradient, for overcoming the vanished gradient issue. A coarse gradient is generated by replacing the a.e. zero derivative of quantized (i.e., staircase) ReLU activation composited in the chain rule with some heuristic proxy derivative called straight-through estimator (STE). Although having been widely used in training quantized networks empirically, fundamental questions like when and why the ad hoc STE trick works, still lack theoretical understanding. In this paper, we propose a class of STEs with certain monotonicity and consider their applications to the training of a two-linear-layer network with quantized activation functions for nonlinear multi-category classification. We establish performance guarantees for the proposed STEs by showing that the corresponding coarse gradient methods converge to the global minimum, which leads to a perfect classification. Lastly, we present experimental results on synthetic data as well as MNIST dataset to verify our theoretical findings and demonstrate the effectiveness of our proposed STEs.
Computing models for quotients of modular curves
Authors: Box Josha 
Published: July 2021

AbstractWe describe an algorithm for computing a$${\mathbb {Q}}$$Q-rational model for the quotient of a modular curve by an automorphism group, under mild assumptions on the curve and the automorphisms, by determiningq-expansions for a basis of the corresponding space of cusp forms. We also give a moduli interpretation for general morphisms between modular curves.
Sport for a Livelihood and Well-being: From Leisure Activity to Occupational Devotion
Authors: Hallmann Kirstin , Bogner Laura , Sander Kathrin , Reuß Konrad 
Published: July 2021

AbstractThis study explored the occupational devotion of lifestyle entrepreneurs and their well-being. Although the number of enterprises in the sports industry increased over the past years, limited literature exists on this topic. Therefore, this paper focused on lifestyle entrepreneurs who turned their sports into their occupations. We conducted semi-structured interviews and a follow-up survey with lifestyle entrepreneurs (N = 13) from various sports (e.g., yoga, kiting, football). The thematic analysis revealed a strong connection between the individuals’ choice of career and well-being. Other themes (and sub-themes), such as mental and physical health and value (co-)creation, were identified, corroborating the authors’ assumption that these lifestyle entrepreneurs started a career in their sports to reach a higher quality of life. The results uncovered that well-being and occupational devotion are closely linked. Co-creation is connected to well-being, and this can accrue social capital in the community. Thus, the results recommended support for lifestyle entrepreneurs as they provide community benefits.
Unsteady pressure measurement and numerical simulations in an end-wall region of a linear blade cascade
Authors: Flídr Erik , Straka Petr , Kladrubský Milan , Jelínek Tomáš 
Published: July 2021

AbstractThis contribution describes experimental and numerical research of an unsteady behaviour of a flow in an end-wall region of a linear nozzle cascade. Effects of compressibility ($$M_\mathrm {2,is}$$

M

2
,
is

) and inlet flow angle ($$\alpha _1$$

α
1

) were investigated. Reynolds number ($$Re_\mathrm {2,is}$$

R

e

2
,
is

$$=8.5\times 10^5$$

=
8.5
×

10
5

) was held constant for all tested cases. Unsteady pressure measurement was performed at the blade mid-span in the identical position $${\mathfrak {s}}$$
s
to obtain reference data. Surface flow visualizations were performed as well as the steady pressure measurement to support conclusions obtained from the unsteady measurements. Comparison of the surface Mach number distributions obtained from the experiments and from the numerical simulations are presented. Flow visualizations are then compared with calculated limiting streamlines on the blade suction surface. It was shown, that the flow structures in the end-wall region were not affected by the primary flow at the blade mid-span, even when the shock wave formed. This conclusion was made from the experimental, numerical, steady as well as unsteady points of view. Three significant frequencies in the power spectra suggested that there was a periodical interaction between the vortex structures in the end-wall region. Based on the data analyses, anisotropic turbulence was observed in the cascade.
Preventing Pressure Oscillations Does Not Fix Local Linear Stability Issues of Entropy-Based Split-Form High-Order Schemes
Authors: Ranocha Hendrik , Gassner Gregor J. 
Published: July 2021

AbstractRecently, it was discovered that the entropy-conserving/dissipative high-order split-form discontinuous Galerkin discretizations have robustness issues when trying to solve the simple density wave propagation example for the compressible Euler equations. The issue is related to missing local linear stability, i.e., the stability of the discretization towards perturbations added to a stable base flow. This is strongly related to an anti-diffusion mechanism, that is inherent in entropy-conserving two-point fluxes, which are a key ingredient for the high-order discontinuous Galerkin extension. In this paper, we investigate if pressure equilibrium preservation is a remedy to these recently found local linear stability issues of entropy-conservative/dissipative high-order split-form discontinuous Galerkin methods for the compressible Euler equations. Pressure equilibrium preservation describes the property of a discretization to keep pressure and velocity constant for pure density wave propagation. We present the full theoretical derivation, analysis, and show corresponding numerical results to underline our findings. In addition, we characterize numerical fluxes for the Euler equations that are entropy-conservative, kinetic-energy-preserving, pressure-equilibrium-preserving, and have a density flux that does not depend on the pressure. The source code to reproduce all numerical experiments presented in this article is available online (https://doi.org/10.5281/zenodo.4054366).
The Nature of Fear Among Farmers Working with Animal Production
Authors: Ceccato Vania , Lundqvist Peter , Abraham Jonatan , Göransson Eva , Alwall Svennefelt Catharina 
Published: July 2021

AbstractIn this article, we investigate the nature of fear among farmers working with animal production with particular focus on the impact of harassment and crimes linked to animal rights activism. The study is based on responses from 3815 animal farmers to a national survey in 2020 in Sweden. Cross-table analysis and logistic regression models underlie the methodology of the study. Findings show that three out of ten of those farmers feel afraid of being victimized by the actions of animal rights activists; the proportion is two-thirds among farmers with previous experience of victimization, and fear of victimization varies across Sweden and by type of activity. Perceived lack of support from the police, exacerbated by geographical isolation, are common determinants of farmers’ declared fear, particularly those whose families live on the farms and who have employees. While understanding the factors that affect farmers’ safety perceptions is important, the article ends by calling for further research on the ways by which fear of animal activism impacts farmers’ personal lives, those of their family and employees, and not least their livelihood.