bluuebunny/crossref_metadata_2025_split huggingface dataset:
Self-assembly of robust gold nanoparticle monolayer architectures for quantitative protein interaction analysis by LSPR spectroscopy
Authors: Flesch Julia , Kappen Marie , Drees Christoph , You Changjiang , Piehler Jacob 
Published: March 2020

AbstractLocalized surface plasmon resonance (LSPR) detection offers highly sensitive label-free detection of biomolecular interactions. Simple and robust surface architectures compatible with real-time detection in a flow-through system are required for broad application in quantitative interaction analysis. Here, we established self-assembly of a functionalized gold nanoparticle (AuNP) monolayer on a glass substrate for stable, yet reversible immobilization of Histidine-tagged proteins. To this end, one-step coating of glass substrates with poly-L-lysine graft poly(ethylene glycol) functionalized with ortho-pyridyl disulfide (PLL-PEG-OPSS) was employed as a reactive, yet biocompatible monolayer to self-assemble AuNP into a LSPR active monolayer. Site-specific, reversible immobilization of His-tagged proteins was accomplished by coating the AuNP monolayer with tris-nitrilotriacetic acid (trisNTA) PEG disulfide. LSPR spectroscopy detection of protein binding on these biocompatible functionalized AuNP monolayers confirms high stability under various harsh analytical conditions. These features were successfully employed to demonstrate unbiased kinetic analysis of cytokine-receptor interactions.
Human ovarian cancer intrinsic mechanisms regulate lymphocyte activation in response to immune checkpoint blockade
Authors: Natoli Marina , Bonito Nair , Robinson James D. , Ghaem-Maghami Sadaf , Mao Yumeng 
Published: March 2020

AbstractImmune checkpoint blocking antibodies are currently being tested in ovarian cancer (OC) patients and have shown some responses in early clinical trials. However, it remains unclear how human OC cancer cells regulate lymphocyte activation in response to therapy. In this study, we have established and optimised an in vitro tumour-immune co-culture system (TICS), which is specifically designed to quantify the activation of multiple primary human lymphocyte subsets and human cancer cell killing in response to PD-1/L1 blockade. Human OC cell lines and treatment naïve patient ascites show differential effects on lymphocyte activation and respond differently to PD-1 blocking antibody nivolumab in TICS. Using paired OC cell lines established prior to and after chemotherapy relapse, our data reveal that the resistant cells express low levels of HLA and respond poorly to nivolumab, relative to the treatment naïve cells. In accordance, knockdown of IFNγ receptor expression compromises response to nivolumab in the treatment naïve OC cell line, while enhanced HLA expression induced by a DNA methyltransferase inhibitor promotes lymphocyte activation in TICS. Altogether, our results suggest a ‘cross resistance’ model, where the acquired chemotherapy resistance in cancer cells may confer resistance to immune checkpoint blockade therapy through down-regulation of antigen presentation machinery. As such, agents that can restore HLA expression may be a suitable combination partner for immunotherapy in chemotherapy-relapsed human ovarian cancer patients.
Radiation exposure during retrograde intrarenal surgery (RIRS): a prospective multicenter evaluation
Authors: Hein Simon , Wilhelm Konrad , Miernik Arkadiusz , Schoenthaler Martin , Suarez-Ibarrola Rodrigo , Gratzke Christian , Salem Johannes , Karapanos Leonidas , Netsch Christopher , Becker Benedikt , Secker Armin , Veser Julian , Neisius Andreas , Fritsche Hans-Martin , Schnabel Marco Julius 
Published: March 2020

Abstract
Purpose
Retrograde intrarenal surgery (RIRS) may require extensive X-ray usage. We evaluated the impact of preoperative surgeon briefing regarding the inclusion and evaluation of fluoroscopy time (FT) and dose area product (DAP) in a multicenter study on the applied X-ray usage.

Methods
A prospective multicenter study of 6 tertiary centers was performed. Each center recruited up to 25 prospective patients with renal stones of any size for RIRS. Prior to study´s onset, all surgeons were briefed about hazards of radiation and on strategies to avoid high doses in RIRS. Prospective procedures were compared to past procedures, as baseline data. FT was defined as the primary outcome. Secondary parameters were stone-free rate (SFR), complications according to the Clavien, SATAVA and postureteroscopic lesion scale. Results were analyzed using T test, chi-squared test, univariate analysis and confirmed in a multivariate regression model.

Results
303 patients were included (145 retro- and 158 prospective). Mean FT and DAP were reduced from 130.8 s/565.8 to 77.4 s/357.8 (p < 0.05). SFR was improved from 85.5% to 93% (p < 0.05). Complications did not vary significantly. Neither stone position (p = 0.569), prestenting (p = 0.419), nor surgeons’ experience (> 100 RIRS) had a significant impact on FT. Significant univariate parameters were confirmed in a multivariate model, revealing X-ray training to be radiation protective (OR − 44, p = 0.001).

Conclusions
Increased surgeon awareness of X-ray exposure risks has a significant impact on FT and DAP. This “awareness effect” is a simple method to reduce radiation exposure for the patient and OR staff without the procedures´ outcome and safety being affected.
A mating-of-trees approach for graph distances in random planar maps
Authors: Gwynne Ewain , Holden Nina , Sun Xin 
Published: March 2020

AbstractWe introduce a general technique for proving estimates for certain random planar maps which belong to the $$\gamma $$
γ
-Liouville quantum gravity (LQG) universality class for $$\gamma \in (0,2)$$

γ
∈
(
0
,
2
)

. The family of random planar maps we consider are those which can be encoded by a two-dimensional random walk with i.i.d. increments via a mating-of-trees bijection, and includes the uniform infinite planar triangulation (UIPT; $$\gamma =\sqrt{8/3}$$

γ
=

8
/
3

); and planar maps weighted by the number of different spanning trees ($$\gamma =\sqrt{2}$$

γ
=

2

), bipolar orientations ($$\gamma =\sqrt{4/3}$$

γ
=

4
/
3

), or Schnyder woods ($$\gamma =1$$

γ
=
1

) that can be put on the map. Using our technique, we prove estimates for graph distances in the above family of random planar maps. In particular, we obtain non-trivial upper and lower bounds for the cardinality of a graph distance ball consistent with the Watabiki (Prog Theor Phys Suppl 114:1–17, 1993) prediction for the Hausdorff dimension of $$\gamma $$
γ
-LQG and we establish the existence of an exponent for certain distances in the map. The basic idea of our approach is to compare a given random planar map M to a mated-CRT map—a random planar map constructed from a correlated two-dimensional Brownian motion—using a strong coupling (Zaitsev in ESAIM Probab Stat 2:41–108, 1998) of the encoding walk for M and the Brownian motion used to construct the mated-CRT map. This allows us to deduce estimates for graph distances in M from the estimates for graph distances in the mated-CRT map which we proved (using continuum theory) in a previous work. In the special case when $$\gamma =\sqrt{8/3}$$

γ
=

8
/
3

, we instead deduce estimates for the $$\sqrt{8/3}$$

8
/
3

-mated-CRT map from known results for the UIPT. The arguments of this paper do not directly use SLE/LQG, and can be read without any knowledge of these objects.
FERM domain–containing protein 6 identifies a subpopulation of varicose nerve fibers in different vertebrate species
Authors: Beck Josefa , Kressel Michael 
Published: March 2020

AbstractFERM domain–containing protein 6 (FRMD6) is a member of the FERM protein superfamily, which is evolutionary highly conserved and has recently been identified as an upstream regulator of the conserved growth-promoting Hippo signaling pathway. In clinical studies, the FRMD6 gene is correlated with high significance to Alzheimer’s disease and cognitive impairment implicating a wider role of this protein in the nervous system. Scare data are available on the localization of endogenous FRMD6 in neural tissues. Using a FRMD6-directed antiserum, we detected specific immunoreactivity in varicose nerve fibers in the rat central and peripheral nervous system. FRMD6-immunoreactive (-ir) neurons were found in the sensory ganglia of cranial nerves, which were marked by a pool of labeled cytoplasmic granules. Cross-species comparative studies detected a morphologically identical fiber population and a comparable fiber distribution in tissues from xenopus and human cranial nerves and ganglia. In the spinal cord, FRMD6-ir was detectable in the terminal endings of primary afferent neurons containing substance P (SP). In the rat diencephalon, FRMD6-ir was co-localized with either SP- or arginine vasopressin–positive fibers in Broca’s diagonal band and the lateral septum. Dense fiber terminals containing both FRMD6-ir and growth hormone-releasing hormone were found in the median eminence. The intimate association of FRMD6 with secretory vesicles was investigated in vitro. Induction of exocytotic vesicles in cultured cells by ectopic expression of the SP precursor molecule preprotachykinin A led to a redistribution and co-localization of endogenous FRMD6 with secretory granules closely mimicking the observations in tissues.
Modeling functional requirements using tacit knowledge: a design science research methodology informed approach
Authors: Benfell Adrian 
Published: March 2020

AbstractThe research in this paper adds to the discussion linked to the challenge of capturing and modeling tacit knowledge throughout software development projects. The issue emerged when modeling functional requirements during a project for a client. However, using the design science research methodology at a particular point in the project helped to create an artifact, a functional requirements modeling technique, that resolved the issue with tacit knowledge. Accordingly, this paper includes research based upon the stages of the design science research methodology to design and test the artifact in an observable situation, empirically grounding the research undertaken. An integral component of the design science research methodology, the knowledge base, assimilated structuration and semiotic theories so that other researchers can test the validity of the artifact created. First, structuration theory helped to identify how tacit knowledge is communicated and can be understood when modeling functional requirements for new software. Second, structuration theory prescribed the application of semiotics which facilitated the development of the artifact. Additionally, following the stages of the design science research methodology and associated tasks allows the research to be reproduced in other software development contexts. As a positive outcome, using the functional requirements modeling technique created, specifically for obtaining tacit knowledge on the software development project, indicates that using such knowledge increases the likelihood of deploying software successfully.
Functional analysis of suspected splicing variants in CLCN5 gene in Dent disease 1
Authors: Inoue Tomohiko , Nagano China , Matsuo Masafumi , Yamamura Tomohiko , Sakakibara Nana , Horinouchi Tomoko , Shibagaki Yugo , Ichikawa Daisuke , Aoto Yuya , Ishiko Shinya , Ishimori Shingo , Rossanti Rini , Iijima Kazumoto , Nozu Kandai 
Published: March 2020

Abstract
Background
In recent years, the elucidation of splicing abnormalities as a cause of hereditary diseases has progressed. However, there are no comprehensive reports of suspected splicing variants in the CLCN5 gene in Dent disease cases. We reproduced gene mutations by mutagenesis, inserted the mutated genes into minigene vectors, and investigated the pathogenicity and onset mechanisms of these variants.

Methods
We conducted functional splicing assays using a hybrid minigene for six suspected splicing variants (c.105G>A, c.105+5G>C, c.106−17T>G, c.393+4A>G, c.517−8A>G, c.517−3C>A) in CLCN5. We extracted information on these variants from the Human Gene Mutation Database. We reproduced minigene vectors with the insertion of relevant exons with suspected splicing variants. We then transfected these minigene vectors into cultured cells and extracted and analyzed the mRNA. In addition, we conducted in silico analysis to confirm our minigene assay results.

Results
We successfully determined that five of these six variants are pathogenic via the production of splicing abnormalities. One showed only normal transcript production and was thus suspected of not being pathogenic (c.106−17T>G).

Conclusion
We found that five CLCN5 variants disrupted the original splice site, resulting in aberrant splicing. It is sometimes difficult to obtain mRNA from patient samples because of the fragility of mRNA or its low expression level in peripheral leukocytes. Our in vitro system can be used as an alternative to in vivo assays to determine the pathogenicity of suspected splicing variants.
An adaptive discontinuous Galerkin method for the simulation of hurricane storm surge
Authors: Beisiegel Nicole , Vater Stefan , Behrens Jörn , Dias Frédéric 
Published: March 2020

AbstractNumerical simulations based on solving the 2D shallow water equations using a discontinuous Galerkin (DG) discretisation have evolved to be a viable tool for many geophysical applications. In the context of flood modelling, however, they have not yet been methodologically studied to a large extent. Systematic model testing is non-trivial as no comprehensive collection of numerical test cases exists to ensure the correctness of the implementation. Hence, the first part of this manuscript aims at collecting test cases from the literature that are generally useful for storm surge modellers and can be used to benchmark codes. On geographic scale, hurricane storm surge can be interpreted as a localised phenomenon making it ideally suited for adaptive mesh refinement (AMR). Past studies employing dynamic AMR have exclusively focused on nested meshes. For that reason, we have developed a DG storm surge model on a triangular and dynamically adaptive mesh. In order to increase computational efficiency, the refinement is driven by physics-based refinement indicators capturing major model sensitivities. Using idealised numerical test cases, we demonstrate the model’s ability to correctly represent all source terms and reproduce known variability of coastal flooding with respect to hurricane characteristics such as size and approach speed. Finally, the adaptive mesh significantly reduces computing time with no effect on storm waves measured at discrete wave gauges just off the coast which shows the model’s potential for use as a robust simulation tool for real-time predictions.
Institutional conditions and social innovations in emerging economies: insights from Mexican enterprises’ initiatives for protecting/preventing the effect of violent events
Authors: Guerrero Maribel , Urbano David 
Published: March 2020

AbstractLatin-American countries are characterised by societal problems like violence, crime, corruption, the informality that influence any entrepreneurial activity developed by individuals/organisations. Social innovations literature confront “wicked problems” with strong interdependencies among different systems/actors. Yet, little is known about how firms use innovation to hedge against economic, political or societal uncertainties (i.e., violence, social movements, democratisation, pandemic). By translating social innovation and institutional theory approaches, this study analyses the influence of formal institutions (government programs and actions) and informal institutions (corruption, extortion and informal trade) on the development/implementation of enterprises’ technological initiatives for protecting/preventing of victimisation. By using data from 5525 establishments interviewed in the 2012/2014 National Victimisation Survey of the Mexican National Institute of Statistics and Geography (INEGI), our findings shows that formal conditions (government programs) and informal conditions (corruption, extortion and informal trade) are associated with an increment in the number of enterprises’ social innovations. Our findings also contribute to the debate about institutional conditions, social innovations, and the role of ecosystems’ actors in developing economies. A provoking discussion and implications for researchers, managers and policymakers emerge from this study.
Explaining Deviatoric Residual Stresses in Aluminum Matrix Composites with Complex Microstructure
Authors: Evsevleev S. , Sevostianov I. , Mishurova T. , Hofmann M. , Garcés G. , Bruno G. 
Published: March 2020

AbstractThe residual stresses in multiphase metal matrix composites with both random planar-oriented short fibers and particles were studied by neutron diffraction and by a model based on the reformulation of classic Maxwell’s homogenization method. Contrary to common understanding and state-of-the-art models, we experimentally observed that randomly oriented phases possess non-hydrostatic residual stress. The recently developed modeling approach allows calculating the residual stress inallphases of the composites. It rationalizes the presence of deviatoric stresses accounting for the interaction of random oriented phases with fibers having preferential orientation.
Statistical Analysis and Evaluation of Macroeconomic Policies: A Selective Review
Authors: Liu Ze-qin , Cai Zong-wu , Fang Ying , Lin Ming 
Published: March 2020

AbstractIn this paper, we highlight some recent developments of a new route to evaluate macroeconomic policy effects, which are investigated under the framework with potential outcomes. First, this paper begins with a brief introduction of the basic model setup in modern econometric analysis of program evaluation. Secondly, primary attention goes to the focus on causal effect estimation of macroeconomic policy with single time series data together with some extensions to multiple time series data. Furthermore, we examine the connection of this new approach to traditional macroeconomic models for policy analysis and evaluation. Finally, we conclude by addressing some possible future research directions in statistics and econometrics.
Effect of enhanced supply air filtration in buildings on protecting citizens from environmental radioactive particles
Authors: Kulmala Ilpo , Zwęgliński Tomasz , Smolarkiewicz Marcin , Salmela Hannu , Kalliohaka Tapio , Taipale Aimo , Kataja Jari , Mäkipää Vesa 
Published: March 2020

AbstractThe effect of enhanced filtration on protection citizens staying indoor against airborne radionuclides released during nuclear core melt accidents was determined by field measurements using outdoor particles as simulants. An electrically enhanced filter was installed in the HVAC system of an office building and its removal efficiency for particles was altered by using a separate particle charging section in power on and off positions. The effect of air filtration on indoor particle concentrations was determined by using an automated measurement system which was continuously sampling from the outdoor air, filtered supply air and exhaust air. With the aid of the measured outdoor and modelled indoor concentrations the indoor/outdoor ratio of particles of outdoor origin could be accurately determined. External charging of the particles increased the electret filters removal efficiency for 0.4 µrn size particles from 60% to 95%, resulting in decrease of the average I/O ratio of the same size particles from 0.67 to 0.40. Despite the high improvement in the supply air filtration efficiency the indoor concentrations decreased only modestly which is likely due to the leaky construction of the building, demonstrating the detrimental effect of air infiltration on the protection provided by buildings against outdoor airborne hazards. Practical implications: The developed method allows quantification of the key parameters affecting the protection of buildings against outdoor contaminants, thus allowing accurate estimation of size resolved indoor to outdoor ratios for fine particles. The electrically enhanced filter can remove effectively also submicron particles thus reducing the occupant exposure to outdoor hazardous or harmful materials. Best results can be achieved with airtight buildings.
Discrepancy Between Fasting Flow-Mediated Dilation and Parameter of Lipids in Blood: A Randomized Exploratory Study of the Effect of Omega-3 Fatty Acid Ethyl Esters on Vascular Endothelial Function in Patients With Hyperlipidemia
Authors: Teramoto Tamio , Shibata Hirotaka , Suzaki Yuki , Matsui Shingo , Uemura Naoto , Tomiyama Hirofumi , Yamashina Akira 
Published: March 2020

Abstract
Introduction
Omega-3 fatty acid ethyl esters (omega-3), an eicosapentaenoic acid and docosahexaenoic acid preparation (Lotriga®, Takeda Pharmaceutical Company Limited), are approved in Japan to treat triglyceridemia. We investigated the effects of omega-3 on vascular endothelial function, measured by flow-mediated dilation (FMD).

Methods
Patients with dyslipidemia receiving 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors were randomized 1:1 to receive omega-3 at 2 g (QD) or 4 g (2 g BID) for 8 weeks. The primary end point was the change from baseline of fasting %FMD in each treatment group. Secondary end points included the 4-h postprandial %FMD and 4-h postprandial triglyceride (TG) level.

Results
Thirty-seven patients were randomized to receive omega-3 at 2 g (n = 18) or 4 g (n = 19). Mean fasting %FMD did not increase from baseline to week 8 in the 2-g group (− 1.2%) or 4-g group (− 1.3%). Mean 4-h postprandial %FMD did not change from baseline to week 8 in the 2-g group (0.0%), but increased in the 4-g group (1.0%). Mean 4-h postprandial TG level decreased by 34.7 mg/dl from baseline over week 8 in the 2-g group, with a significantly larger decrease in the 4-g group of 75.9 mg/dl (p < 0.001). No new safety concerns were identified.

Conclusions
Fasting %FMD did not improve after 8 weeks of omega-3 treatment at 2 g or 4 g. After 8 weeks, 4-h postprandial TG levels showed improvement at both doses, with a greater reduction in the 4-g group.

Trial Registration
ClinicalTrials.gov, ID: NCT02824432.