bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pro-inflammatory cytokines induce cell death, inflammatory responses, and endoplasmic reticulum stress in human iPSC-derived beta cells
Authors: Demine Stéphane , Schiavo Andrea Alex , Marín-Cañas Sandra , Marchetti Piero , Cnop Miriam , Eizirik Decio L. 
Published: January 2020

Abstract
Background
Adult human pancreatic beta cells are the “gold standard” for studies on diabetes pathogenesis, but their use is limited by insufficient availability and variable quality. An important effort has recently taken place to differentiate beta cells from human induced pluripotent stem cells (iPSCs) and validate their use for diabetes research. We presently used a 7-stage protocol to generate beta cells from human iPSC and evaluated whether these cells are responsive to the pro-inflammatory cytokines (IFNγ, IL-1β, or IFNα) that play a role in type 1 diabetes.

Methods
The iPSC-derived islet-like cell clusters contained 40–50% beta and 10–15% alpha cells and expressed the receptors for IFNγ, IL-1β, or IFNα. Cells were exposed to either IFNγ (1000 U/mL) + IL-1β (50 U/mL) or IFNα alone (2000 U/mL) for 24/48 h. Apoptosis was quantified using Hoechst/propidium iodide staining or the RealTime Glo Apoptosis Kit (Promega). After treatment, CXCL10 secretion was quantified by ELISA. The expression of multiples genes (Ins, Gcg, Nkx2.2, Nkx6.1, Pdx1, Mafa, BiP, Chop, Atf3, CXCL10, CXCL9, CCL5, and HLA-ABC) was quantified by RT-qPCR. Phosphorylation state and total expression of STAT1/STAT2, as well as expression of PDL1 and of the ER chaperone BiP, were quantified by Western blotting. The co-localization of HLA-ABC or cleaved caspase-3 and Ins/Gcg expression was assessed by immunohistochemistry. The presence of HLA-ABC at the plasma membrane was measured by flow cytometry.

Results
IFNγ + IL-1β and IFNα induced apoptosis of the cells after 48 h of exposure. Cleaved caspase-3 co-localized mostly but not exclusively with Ins+ cells. Exposure to IFNγ + IL-1β induced a pro-inflammatory phenotype, including increased CXCL10, CXCL9, and CCL5 expression; CXCL10 secretion; and HLA-ABC expression. HLA overexpression was confirmed at the protein level by Western blotting and flow cytometry. Exposure to IFNγ + IL-1β (but not IFNα) also induced beta cell dedifferentiation and endoplasmic reticulum stress (increase in BiP, Chop, and Atf3 mRNA expression). Phosphorylation of STAT1 was stimulated already after 1 h by IFNγ + IL-1β and IFNα, while phosphorylation of STAT2 was only activated by IFNα at 1–4 h. PDL1 expression was increased by both IFNγ + IL-1β and IFNα.

Conclusions
Our data show that human iPSC-derived beta cells respond to pro-inflammatory cytokines IL-1β + IFNγ and IFNα, by activating the same pathogenic processes as adult human primary beta cells. These cells thus represent a valuable tool for future research on the pathogenesis of type 1 diabetes.
Preconditioning of mesenchymal stromal cells with low-intensity ultrasound: influence on chondrogenesis and directed SOX9 signaling pathways
Authors: Sahu Neety , Budhiraja Gaurav , Subramanian Anuradha 
Published: January 2020

AbstractBackgroundContinuous low-intensity ultrasound (cLIUS) facilitates the chondrogenic differentiation of human mesenchymal stromal cells (MSCs) in the absence of exogenously added transforming growth factor-beta (TGFβ) by upregulating the expression of transcription factor SOX9, a master regulator of chondrogenesis. The present study evaluated the molecular events associated with the signaling pathways impacting SOX9 gene and protein expression under cLIUS.MethodsHuman bone marrow-derived MSCs were exposed to cLIUS stimulation at 14 kPa (5 MHz, 2.5 Vpp) for 5 min. The gene and protein expression of SOX9 was evaluated. The specificity ofSOX9upregulation under cLIUS was determined by treating the MSCs with small molecule inhibitors of select signaling molecules, followed by cLIUS treatment. Signaling events regulatingSOX9expression under cLIUS were analyzed by gene expression, immunofluorescence staining, and western blotting.ResultscLIUS upregulated the gene expression ofSOX9and enhanced the nuclear localization of SOX9 protein when compared to non-cLIUS-stimulated control. cLIUS was noted to enhance the phosphorylation of the signaling molecule ERK1/2. Inhibition of MEK/ERK1/2 by PD98059 resulted in the effective abrogation of cLIUS-inducedSOX9expression, indicating that cLIUS-inducedSOX9upregulation was dependent on the phosphorylation of ERK1/2. Inhibition of integrin and TRPV4, the upstream cell-surface effectors of ERK1/2, did not inhibit the phosphorylation of ERK1/2 and therefore did not abrogate cLIUS-inducedSOX9expression, thereby suggesting the involvement of other mechanoreceptors. Consequently, the effect of cLIUS on the actin cytoskeleton, a mechanosensitive receptor regulatingSOX9, was evaluated. Diffused and disrupted actin fibers observed in MSCs under cLIUS closely resembled actin disruption by treatment with cytoskeletal drug Y27632, which is known to increase the gene expression ofSOX9. The upregulation ofSOX9under cLIUS was, therefore, related to cLIUS-induced actin reorganization.SOX9upregulation induced by actin reorganization was also found to be dependent on the phosphorylation of ERK1/2.ConclusionsCollectively, preconditioning of MSCs by cLIUS resulted in the nuclear localization of SOX9, phosphorylation of ERK1/2 and disruption of actin filaments, and the expression ofSOX9was dependent on the phosphorylation of ERK1/2 under cLIUS.
Nonlinear conservation laws for the Schrödinger boundary value problems of second order
Authors: Ren Ming , Yun Shiwei , Li Zhenping 
Published: January 2020

AbstractIn this paper, we apply a reliable combination of maximum modulus method with respect to the Schrödinger operator and Phragmén–Lindelöf method to investigate nonlinear conservation laws for the Schrödinger boundary value problems of second order. As an application, we prove the global existence to the solution for the Cauchy problem of the semilinear Schrödinger equation. The results reveal that this method is effective and simple.
The Prognostic Index Independently Predicts Survival in Patients with Pancreatic Ductal Adenocarcinoma Undergoing Resection
Authors: Gruber Elisabeth S. , Jomrich Gerd , Kaider Alexandra , Gnant Michael , Sahora Klaus , Schindl Martin 
Published: January 2020

Abstract
Background
Cancer-related inflammation is associated with tumour proliferation, maintenance and dissemination. It therefore impacts pancreatic cancer survival. The goal of this study was to examine the Prognostic Index (PI) as a prognostic biomarker for survival in patients with pancreatic ductal adenocarcinoma (PDAC). In addition, we explored factors known to interact with the immune and inflammation cascade that might interfere with the PI’s strength for prognostication.

Methods
Patients with PDAC undergoing resection were analysed retrospectively. The PI was calculated from preoperatively derived C-reactive protein levels and white blood count. Data were subject to correlation and survival analysis.

Results
Of 357 patients, 235 (65.8%) patients had a PI 0, 108 (30.3%) PI 1, and 14 (3.9%) PI 2. Median (quartiles) survival with a high PI (group 1 + 2) was 13.2 months (7.7–27.0), compared with 18.7 months (10.2–35.4) with a low PI (group 0; p = 0.012). The PI proved to be an independent prognostic factor for cancer-specific survival (p = 0.003) adjusted for conventional prognostic factors. Prognostic strength was influenced by the presence of a bile stent (p = 0.032).

Conclusions
The PI is a strong and solid independent prognostic tool for survival in patients with PDAC undergoing resection. Preoperative survey of inflammatory activity as provided by the use of a biomarker like the PI may help to identify those patients at risk of a poor prognosis.
(NON) HUMAN(IMAL) RIGHTS: DISMANTLING THE SEPARATENESS IN LAW AND POLICY
Authors: WILSON AMY P. 
Published: January 2020

In 2016, the South African Constitutional Court recognised that the guaranteed human right to the environment, as contained in the Constitution, includes animal welfare. In its judgment, the court stated that the suffering of individual animals is correctly linked to conservation and that this “illustrates the extent to which showing respect and concern for individual animals reinforces broader environmental protections. Animal welfare and animal conservation together reflect two intertwined values”. Although the effect of the statement by the highest court in the land is yet to be fully realised, the court unambiguously demonstrated in its ruling the clear link between human rights and animal interests. These interests are not only to be interpreted in the broad sense relating to species-conservation, but rather the interests and welfare of individual animals.
Building on from this approach and the rationale provided by the court, this Paper looks to explore more broadly the interaction and linkages between human and animal rights and interests. More particularly, it attempts to illustrate how these concepts may reinforce and enrich one another and how this relationship may be better reflected in law and policy. It will argue that sophisticated democracies and movements require an integrational approach. By expanding the scope and interpretation of certain human rights to include animal interests; and through coordinated, targeted efforts – we ensure notion of justice is achieved, for all who require it.
Further structural studies of the lytic polysaccharide monooxygenase AoAA13 belonging to the starch-active AA13 family
Authors: Muderspach Sebastian J. , Tandrup Tobias , Frandsen Kristian E. H. , Santoni Gianluca , Poulsen Jens-Christian N. , Leggio Leila Lo 
Published: January 2020

Abstract
Lytic polysaccharide monooxygenases (LPMOs) are recently discovered copper enzymes that cleave recalcitrant polysaccharides by oxidation. The structure of an Aspergillus oryzae LPMO from the starch degrading family AA13 (AoAA13) has previously been determined from an orthorhombic crystal grown in the presence of copper, which is photoreduced in the structure. Here we describe how crystals reliably grown in presence of Zn can be Cu-loaded post crystallization. A partly photoreduced structure was obtained by severely limiting the X-ray dose, showing that this LPMO is much more prone to photoreduction than others. A serial synchrotron crystallography structure was also obtained, showing that this technique may be promising for further studies, to reduce even further photoreduction. We additionally present a triclinic structure of AoAA13, which has less occluded ligand binding site than the orthorhombic one. The availability of the triclinic crystals prompted new ligand binding studies, which lead us to the conclusion that small starch analogues do not bind to AoAA13 to an appreciable extent. A number of disordered conformations of the metal binding histidine brace have been encountered in this and other studies, and we have previously hypothesized that this disorder may be a consequence of loss of copper. We performed molecular dynamics in the absence of active site metal, and showed that the dynamics in solution differ somewhat from the disorder observed in the crystal, though the extent is equally dramatic.
Effects of Huaiqihuang Granules adjuvant therapy in children with primary nephrotic syndrome
Authors: Zhou Ping , Xiao Qiong , Chen Lan , Zou Zhi-Jie , Wang Yu-Qing , Zhu Lin , Yu Hai-Yan , Zhao Cheng-Guang , Wu Yu-Bin , Du Xuan-Yi 
Published: January 2020

AbstractObjectiveThis study aims to observe the curative effect of Huaiqihuang Granules adjuvant therapy on primary nephrotic syndrome (PNS).MethodsA total of 112 children with PNS were randomly divided into three groups, and changes in serum inflammatory cytokines, interleukin, lymphocyte subsets and immunoglobulin were observed.ResultsBefore treatment, IL-18, TNF-α, CD8+ increased, while IL-10, CD4+, NK cells, IgA, IgG and Foxp3+Treg cells decreased. After Huaiqihuang Granules treatment, IL-18, TNF-α, CD8+ decreased, while IL-10, CD4+, NK cells, IgA, IgG and Foxp3+Treg cells increased.ConclusionFunctions of cell immunity and humoral immunity in PNS patients before treatment were suppressed and disordered. Huaiqihuang granules can play a role in immunoregulation, with slight side reactions.
Immune negative regulator TIPE2 inhibits cervical squamous cancer progression through Erk1/2 signaling
Authors: Huang Li-Qiong , Zheng Bo , He Yi 
Published: January 2020

AbstractTumor necrosis factor (TNF)-α-induced protein-8-like 2, or TIPE2, is a newly found immune negative regulatory molecule. This study further investigated the role of TIPE2 on proliferation and invasion of cervical squamous cancer cells. Expression of TIPE2 was compared in cervical squamous cancer tissues and adjacent normal tissues by Western blot and immunohistochemistry (IHC). Cervical squamous cancer cell lines, SiHa and C33A, were transfected with recombinant plasmid encoding TIPE2 and tested for cytologic characteristics. The impact of TIPE2 on phosphorylation of extracellular signal-regulated kinase (Erk) signaling pathway was also tested by Western blot analysis of key factors. TIPE2 expression was higher in cervical cancer tissues than that in normal tissue. IHC score of tumor tissue was negatively associated with lymphatic metastasis. Over expression of TIPE2 effectively inhibited the proliferation of cervical cancer cells. Wound healing and transwell assay showed that over expression of TIPE2 suppressed cell migration and invasion in vitro. Meanwhile, phosphorylation of Erk1/2 and upstream mitogen-activated protein kinase kinase (MEK) 1/2 was reduced by TIPE2. TIPE2 is negatively related with development of cervical squamous cancer. TIPE2 is an inhibitory factor of proliferation and invasion of cervical squamous cancer cells, probably through inhibiting Erk signaling pathway.
Some transpose-free CG-like solvers for nonsymmetric ill-posed problems
Authors: Gazzola Silvia , Novati Paolo 
Published: January 2020

AbstractThis paper introduces and analyzes an original class of Krylov subspace methods that provide an efficient alternative to many well-known conjugate-gradient-like (CG-like) Krylov solvers for square nonsymmetric linear systems arising from discretizations of inverse ill-posed problems. The main idea underlying the new methods is to consider some rank-deficient approximations of the transpose of the system matrix, obtained by running the (transpose-free) Arnoldi algorithm, and then apply some Krylov solvers to a formally right-preconditioned system of equations. Theoretical insight is given, and many numerical tests show that the new solvers outperform classical Arnoldi-based or CG-like methods in a variety of situations.
Das Ende des Staatsstreichs
Authors: Heinemann Winfried 
Published: January 2020

Vorspann
Der Staatsstreich, der am Abend des 20. Juli 1944 im Bendlerblock zusammenbrach, wurde nicht von Truppen des Berliner Wachbataillons niedergeschlagen, wie es dessen Kommandeur, der fanatische Nazi Major Otto Ernst Remer, und sein Adjutant Leutnant Hans Wilhelm Hagen, nach dem Krieg immer wieder dargestellt haben. Die ersten, die sich gegen Stauffenberg und dessen Mitverschwörer stellten, waren Offiziere aus dem Stab des Allgemeinen Heeresamts. Drei von ihnen, die Oberstleutnante Herber, von der Heyde und Pridun, wurden kurz darauf bevorzugt zum Oberst befördert; außer den Beförderungen von Remer und Hagen wurde im Wachbataillon kaum jemand belobigt. Nach außen hin aber zog das Regime es vor, den „Frontkämpfer“ und Eichenlaubträger Remer sowie den Reservisten aus dem Reichspropagandaministerium Hagen als die „Männer der Stunde“ herauszustellen, und nicht die Generalstabsoffiziere aus den Büros im Bendlerblock. Auch nach dem Krieg nutzten Remer und Hagen ihre Reputation für ihre rechtsradikalen Bestrebungen, während sich die eigentlichen Umsturzgegner aus dem Bendlerblock in bürgerliche Existenzen zurückzogen und von ihrer Rolle am 20. Juli möglichst wenig wissen wollten.
Der Generaloberst und die Historiker
Authors: Fröhlich Paul 
Published: January 2020

Vorspann
In den 1950er und 1960er Jahren überschwemmte eine Fülle von zeitgeschichtlichen Memoiren, Editionen und Dokumentationen zum NS-Regime beziehungsweise zum Zweiten Weltkrieg den Markt. Wie zuletzt Magnus Brechtken für den Fall Albert Speer zeigte, (ent-)standen einiger dieser Werke unter dem geschichtspolitischen Einfluss der ehemaligen Akteure und dienten einer weit verbreiteten Exkulpationsmentalität. Im Lichte dieser aktuellen Forschungsthemen untersucht Paul Fröhlich die Publikationsgeschichte des Kriegstagebuchs von Franz Halder, Chef des Generalstabs des Heeres zwischen 1938 und 1942. Er zeigt den außerordentlichen Einfluss Halders und dessen Entlastungsnarrative auf die Praxis der zeitgeschichtlichen Forschung seit dem Ende der 1940er Jahre und stellt die Frage nach der Akteursnähe der damaligen Historiker.
Lung Function of Adults Born at Very Low Birth Weight
Authors: Yang Jun , Kingsford Rachel A. , Horwood John , Epton Michael J. , Swanney Maureen P. , Stanton Josh , Darlow Brian A. 
Published: January 2020

BACKGROUND:
Much remains unknown about the consequences of very low birth weight (VLBW) and bronchopulmonary dysplasia (BPD) on adult lungs. We hypothesized that VLBW adults would have impaired lung function compared with controls, and those with a history of BPD would have worse lung function than those without.

METHODS:
At age 26 to 30 years, 226 VLBW survivors of the New Zealand VLBW cohort and 100 term controls born in 1986 underwent lung function tests including spirometry, plethysmographic lung volumes, diffusing capacity of the lung for carbon monoxide, and single-breath nitrogen washout (SBN2).

RESULTS:
An obstructive spirometry pattern was identified in 35% VLBW subjects versus 14% controls, with the majority showing mild obstruction. Compared with controls, VLBW survivors demonstrated significantly lower forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity (FVC) ratio (FEV1/FVC), forced expiratory flow at 25% to 75% of FVC and higher residual volume (RV), RV/total lung capacity (TLC) ratio (RV/TLC), decreased diffusing capacity of the lung for carbon monoxide, and increased phase III slope for SBN2. The differences persisted after adjustment for sex and smoking status. Within the VLBW group, subjects with BPD showed significant reduction in FEV1, FEV1/FVC, and forced expiratory flow at 25% to 75% of FVC, and increase in RV, RV/TLC, and phase III slope for SBN2, versus subjects without. The differences remained after adjustment for confounders.

CONCLUSIONS:
Adult VLBW survivors showed a higher incidence of airflow obstruction, gas trapping, reduced gas exchange, and increased ventilatory inhomogeneity versus controls. The findings suggest pulmonary effects due to VLBW persist into adulthood, and BPD is a further insult on small airway function.
Rhetorical Styles in Knowledge Communication
Authors: Załęska Maria 
Published: January 2020

The author of the article applied the rhetorical framework of three styles (genera dicendi) to highlight some of the communicative practices employed in academic discourse. By utilising the persuasive resources of the plain style, authors focus on the rhetorical purpose of docere/probare, i.e. to teach/to prove. The sober matter-of-factness of the plain style suggests to readers that there is no style at all, convincing them that the content reflects reality without any rhetorical mediation. In choosing the persuasive means of the middle style, researchers combine epistemic and aesthetic goals, trying to reach the rhetoric purpose of delectare, i.e. to delight. An engaging style helps them draw readers into intellectually complex issues. The grand style facilitates the reaching of the rhetorical purpose of movere, i.e. to move or induce action. It serves to present science as a helpful resource for readers to make decisions in their lives, hence it is likely to be used by engaged scholars and public intellectuals.
Linguistic and Stylistic Polyphony of Occasional Journalism
Authors: Wojtak Maria 
Published: January 2020

The article was intended as an attempt at defining a specific press publication in the form of a genre collection. It was the supplement to the Tygodnik Powszechny weekly (issue 29 of 2018) entitled “Festiwal Stolica Języka Polskiego” [Capital of Polish Language Festival]. The publication utilised the form of a press magazine, as apart from the program of the festival, it also included: an editorial, interviews, reviews, commentaries and the bios of selected festival guests. Thus, it offered a cooccurrence of specific statements in a specific place and time which is typical for such a collection. The whole could be assigned the function of announcing a cultural event (the festival), and the function of promoting it. The author analyses the publication from the discursive perspective, i.e. she focussed on specific communicational practices typical for contemporary press, which form a complex network of strategies, goals and forms of communication, which, in turn, form contemporary journalism. The analytical objective of the paper was to present the communicational polyphony of a specific collection of journalistic expressions, that is which interpret a specific reality and were used for convincing the readers to accept that interpretation. Individual texts were treated as voices, i.e. in types of linguistic actions formed in communicational (pragmatic) and formal terms.
Children’s Magazines as Tools for (Not Only) Reading Education
Authors: Adamski Andrzej 
Published: January 2020

The main aim of the article is to answer the question of how children’s magazines may be used as tools for media education understood as educating children on how to process media, and also as instilling the habit of reading periodicals and books. Hypothesis: It is generally assumed in the scholarly literature that periodicals for children may be an effective tool in encouraging a reading habit. Unfortunately, this segment of the press market, just as all other segments, faces declining readership due to the expansion of the digital media. Methodology: An analysis the existing data (e.g. study reports) and academic analyses in terms of the impact of the media, pedagogy, media education, and media psychology. The article is theoretical in nature. It stems from the discipline of the “science of social communication and the media”, yet it offers an interdisciplinary approach, due to its references to pedagogy, education, and technology.
The relationship between teaching styles and SEN students' reading comprehension achievement
Authors: Vlahava Kalliopi , Antoniou Faye 
Published: January 2020

The aim of the current study was to find out which are the characteristics that affect teachersâ€™ preference on specific teaching styles and whether students with Learning Disabilities are benefited by the use of specific teaching styles in the development of their reading comprehension skills. Seventeen English as a Foreign Language teachers and 309 students, 55 of which were identified as students with special educational needs (SEN), aged 9â€“11 years old, were participated in this study. A questionnaire consisting of four teaching scenarios, in order for teachersâ€™ preferred teaching style to be emerged, and a reading comprehension test, which sought to assess studentsâ€™ reading comprehension skill and their skill to draw conclusions based on the information given on the text, was given to the teachers and students, respectively. Results indicated a high teachers' preference for the suggestive teaching style when dealing with students with SEN in the mainstream classroom. Findings also showed that teaching styles have a significant impact on their studentsâ€™ competence of extracting meaning from written text. The most beneficial teaching style to students with SEN was the suggestive one.
Keywords: English as a foreign language, reading comprehension, special educational needs, teaching styles.