bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of DNA-LL37 complexes in the activation of plasmacytoid dendritic cells and monocytes in subjects with type 1 diabetes
Authors: Badal Darshan , Dayal Devi , Singh Gunjan , Sachdeva Naresh 
Published: June 2020

AbstractInitiation of type 1 diabetes (T1D) is marked by the infiltration of plasmacytoid dendritic cells (pDCs) and monocytes in pancreatic islets. Dying beta cells release self-DNA, which forms complexes with antimicrobial peptide, LL37, and its delayed clearance can activate pDCs and monocytes. Here, we studied the phenotypic effects of DNA-LL37 complexes on pDCs and monocytes in 55 recently diagnosed T1D and 25 healthy control (HC) subjects. Following in vitro stimulation with DNA-LL37 complexes, T1D group demonstrated higher frequency and mean fluorescence intensity (MFI) of pDCs expressing IFN-α. Similarly, the monocytes in T1D group showed an increase in MFI of IFN-α. Post-stimulation, an increase in the antigen presentation and co-stimulatory ability of pDCs and monocytes was observed in T1D group, as indicated by higher expression of HLA-DR, CD80 and CD86. Upon co-culture, the stimulated monocytes and pDCs, particularly in the T1D group were able to further activate autologous CD4 + T cells, with increase in expression of CD69 and CD71. Finally, in a transwell assay, the stimulated pDCs and monocytes induced an increase in apoptosis of 1.1B4 beta cells. Additionally, we observed reduced expression of indoleamine 2,3-dioxygenase 1 (IDO1) in pDCs and monocytes of T1D subjects. Our results suggest that DNA-LL37 complexes activate pDCs and monocytes towards a proinflammatory phenotype during pathogenesis of T1D.
Rapid conjugation of antibodies to toxins to select candidates for the development of anticancer Antibody-Drug Conjugates (ADCs)
Authors: Hoffmann Ricarda M. , Mele Silvia , Cheung Anthony , Larcombe-Young Daniel , Bucaite Gintare , Sachouli Eirini , Zlatareva Iva , Morad Hassan O. J. , Marlow Rebecca , McDonnell James M. , Figini Mariangela , Lacy Katie E. , Tutt Andrew J. N. , Spicer James F. , Thurston David E. , Karagiannis Sophia N. , Crescioli Silvia 
Published: June 2020

AbstractAntibody-Drug Conjugates (ADCs) developed as a targeted treatment approach to deliver toxins directly to cancer cells are one of the fastest growing classes of oncology therapeutics, with eight ADCs and two immunotoxins approved for clinical use. However, selection of an optimum target and payload combination, to achieve maximal therapeutic efficacy without excessive toxicity, presents a significant challenge. We have developed a platform to facilitate rapid and cost-effective screening of antibody and toxin combinations for activity and safety, based on streptavidin-biotin conjugation. For antibody selection, we evaluated internalization by target cells using streptavidin-linked antibodies conjugated to biotinylated saporin, a toxin unable to cross cell membranes. For payload selection, we biotinylated toxins and conjugated them to antibodies linked to streptavidin to evaluate antitumour activity and pre-clinical safety. As proof of principle, we compared trastuzumab conjugated to emtansine via streptavidin-biotin (Trastuzumab-SB-DM1) to the clinically approved trastuzumab emtansine (T-DM1). We showed comparable potency in reduction of breast cancer cell survival in vitro and in growth restriction of orthotopic breast cancer xenografts in vivo. Our findings indicate efficient generation of functionally active ADCs. This approach can facilitate the study of antibody and payload combinations for selection of promising candidates for future ADC development.
Structural, mechanical and electronic properties and hardness of ionic vanadium dihydrides under pressure from first-principles computations
Authors: Wang Wenjie , Zhang Chuanzhao , Jin Yuanyuan , Li Song , Zhang Weibin , Kong Panlong , Xie Chengwu , Du Chengzhuo , Liu Qian , Zhang Caihong 
Published: June 2020

AbstractBased on a combination of the CALYPSO method for crystal structure prediction and first-principles calculations, we explore the crystal structures of VH2 under the pressure range of 0−300 GPa. The cubic Fm-3m phase with regular VH8 cubes is predicted to transform into orthorhombic Pnma structure with fascinating distorted VH9 tetrakaidecahedrons at 47.36 GPa. Both the Fm-3m phase at 0 GPa and the Pnma phase at 100 GPa are mechanically and dynamically stable, as verified with the calculations of elastic constants and phonon dispersions, respectively. Moreover, the calculated electronic band structure and density of states indicate both stable phases are metallic. Remarkably, the analyses of the Poisson’s ratio, electron localization function (ELF) and Bader charge substantiate that both stable phases are ionic crystals on account of effective charges transferring from V atom to H. On the basis of the microscopic hardness model, the Fm-3m and Pnma crystals of VH2 are potentially incompressible and hard materials with the hardness values of 17.83 and 17.68 GPa, respectively.
PTH(1–34) treatment and/or mechanical loading have different osteogenic effects on the trabecular and cortical bone in the ovariectomized C57BL/6 mouse
Authors: Roberts Bryant C. , Arredondo Carrera Hector M. , Zanjani-pour Sahand , Boudiffa Maya , Wang Ning , Gartland Alison , Dall’Ara Enrico 
Published: June 2020

AbstractIn preclinical mouse models, a synergistic anabolic response to PTH(1–34) and tibia loading was shown. Whether combined treatment improves bone properties with oestrogen deficiency, a cardinal feature of osteoporosis, remains unknown. This study quantified the individual and combined longitudinal effects of PTH(1–34) and loading on the bone morphometric and densitometric properties in ovariectomised mice. C57BL/6 mice were ovariectomised at 14-weeks-old and treated either with injections of PTH(1–34); compressive loading of the right tibia; both interventions concurrently; or both interventions on alternating weeks. Right tibiae were microCT-scanned from 14 until 24-weeks-old. Trabecular metaphyseal and cortical midshaft morphometric properties, and bone mineral content (BMC) in 40 different regions of the tibia were measured. Mice treated only with loading showed the highest trabecular bone volume fraction at week 22. Cortical thickness was higher with co-treatment than in the mice treated with PTH alone. In the mid-diaphysis, increases in BMC were significantly higher with loading than PTH. In ovariectomised mice, the osteogenic benefits of co-treatment on the trabecular bone were lower than loading alone. However, combined interventions had increased, albeit regionally-dependent, benefits to cortical bone. Increased benefits were largest in the mid-diaphysis and postero-laterally, regions subjected to higher strains under compressive loads.
Trace amines produced by skin bacteria accelerate wound healing in mice
Authors: Luqman Arif , Muttaqin Muhammad Zainul , Yulaipi Sumah , Ebner Patrick , Matsuo Miki , Zabel Susanne , Tribelli Paula Maria , Nieselt Kay , Hidayati Dewi , Götz Friedrich 
Published: June 2020

AbstractCertain skin bacteria are able to convert aromatic amino acids (AAA) into trace amines (TA) that act as neuromodulators. Since the human skin and sweat contain a comparatively high content of AAA one can expect that such bacteria are able to produce TA on our skin. Here we show that TA-producingStaphylococcus epidermidisstrains expressing SadA are predominant on human skin and that TA accelerate wound healing. In wounded skin, keratinocytes produce epinephrine (EPI) that leads to cell motility inhibition by β2-adrenergic receptor (β2-AR) activation thus delay wound healing. As β2-AR antagonists, TA and dopamine (DOP) abrogate the effect of EPI thus accelerating wound healing both in vitro and in a mouse model. In the mouse model, theS. epidermidiswild type strain accelerates wound healing compared to its ΔsadAmutant. Our study demonstrates that TA-producingS. epidermidisstrains present on our skin might be beneficial for wound healing.
Hedgehog signaling activation required for glypican-6-mediated regulation of invasion, migration, and epithelial–mesenchymal transition of gastric cancer cells
Authors: Zeng Chen , Yan Ran , Yang Guanghua , Xiang Sen , Zhao Fuli 
Published: June 2020

Abstract
Gastric cancer (GC) is the fifth most common cancer worldwide and one of the most aggressive cancers in China. Glypican 6 is highly expressed in gastric adenocarcinoma and may act as a diagnostic and prognostic marker; however, the functional importance and molecular mechanism of glypican 6 in GC remains unclear. In the current study, we aimed to reveal the function and mechanism of glypican 6 in two GC cell lines: MKN-45 and SGC-7901. We found higher expression of glypican 6 in MKN-45 and SGC-7901 cells than in cells from the normal gastric mucosa epithelial cell line GES-1. Glypican 6 knockdown suppressed MKN-45 and SGC-7901 cell proliferation. A Transwell assay confirmed that glypican 6 silencing inhibited the migration and invasiveness of MKN-45 and SGC-7901 cells. Epithelial-to-mesenchymal transition (EMT) markers were determined by western blotting, and the results showed reduced Vimentin expression and elevated E-cadherin expression in glypican 6 short interfering RNA (siRNA) transfected MKN-45 and SGC-7901 cells. However, glypican 6 overexpression in GES-1 cells showed no significant promotion on GES-1 cells proliferation and migration. Further studies confirmed that glypican 6 siRNA regulated Hedgehog and Gli1 signaling and participated in the function of glypican 6 on MKN-45 and SGC-7901 cell migration and invasion. Our findings suggest that decreased glypican 6 expression inhibits the migration and invasion ability of GC cells.
Listening Effort in Native and Nonnative English-Speaking Children Using Low Linguistic Single- and Dual-Task Paradigms
Authors: Oosthuizen Ilze , Picou Erin M. , Pottas Lidia , Myburgh Hermanus Carel , Swanepoel De Wet 
Published: June 2020

Purpose
It is not clear if behavioral indices of listening effort are sensitive to changes in signal-to-noise ratio (SNR) for young children (7–12 years old) from multilingual backgrounds. The purpose of this study was to explore the effects of SNR on listening effort in multilingual school-aged children (native English, nonnative English) as measured with a single- and a dual-task paradigm with low-linguistic speech stimuli (digits). The study also aimed to explore age effects on digit triplet recognition and response times (RTs).

Method
Sixty children with normal hearing participated, 30 per language group. Participants completed single and dual tasks in three SNRs (quiet, −10 dB, and −15 dB). Speech stimuli for both tasks were digit triplets. Verbal RTs were the listening effort measure during the single-task paradigm. A visual monitoring task was the secondary task during the dual-task paradigm.

Results
Significant effects of SNR on RTs were evident during both single- and dual-task paradigms. As expected, language background did not affect the pattern of RTs. The data also demonstrate a maturation effect for triplet recognition during both tasks and for RTs during the dual-task only.

Conclusions
Both single- and dual-task paradigms were sensitive to changes in SNR for school-aged children between 7 and 12 years of age. Language background (English as native language vs. English as nonnative language) had no significant effect on triplet recognition or RTs, demonstrating practical utility of low-linguistic stimuli for testing children from multilingual backgrounds.
Thecoperitoneal Shunt Migration through Anus–A Rare Presentation
Authors: Ambekar Sudheer , Vekariya Mayank 
Published: June 2020

AbstractThe thecoperitoneal (TP) shunt is a cerebrospinal fluid (CSF) diversion technique. It is a commonly used technique in many neurosurgical conditions, and many complications are associated with it. This is a case of TP shunt migration through the anus. It is an uncommon and rare presentation of one of the complications associated with the TP shunt. Caregivers should keep this in mind about this complication, as it leads to devastating complications like meningitis and suffering for the patient.
The effect of cultural transmission on shared sign language persistence
Authors: Mudd Katie , de Vos Connie , de Boer Bart 
Published: June 2020

AbstractIn this paper, we revisit a mathematical model of sign language persistence by Aoki and Feldman (Theor Popul Biol 39(3):358–372, 1991), which investigates the evolution of genes causing deafness, affected by an assortative mating parameter, and the cultural transmission of sign language. To assess their model, we reimplement it as an agent-based simulation to be able to easily represent structured relationships in a finite population. We study the persistence of shared sign languages, a categorization of sign languages, which are typically shared by deaf and hearing members of a small community with a high incidence of hereditary deafness (Nyst, 2012. Shared sign languages. Sign language: An international handbook, pp. 552–574). We observe how shared sign language persistence is affected by hearing signers, marriage patterns, and various modes of sign language transmission: vertical, horizontal, oblique, and grandparental transmission. In contrast to Aoki and Feldman’s (Theor Popul Biol 9(3):358–372, 1991) finding that modes of transmission other than vertical are negligible, in the agent-based model we find that adding modes of transmission helps to ensure shared sign language persistence. A better understanding of sign language persistence has relevance for processes of cultural evolution, (sign language) linguistics, and language endangerment.
Sequence and word frequency
Authors: Barlow Michael 
Published: June 2020

Abstract
It is well-established that the linear ordering of words in a sentence is influenced by a variety of factors that are typically labelled as grammatical, discourse or cognitive constraints. The aim of the present study is to determine whether frequency effects are visible in the sequencing of words in a sentence. In other words, do “more frequently used units tend to be placed before less frequently used units” (Fenk-Oczlon 2001: 443)? Using a corpus of newspaper articles, we examine the frequency of words in different positions in sentences. That is, using data from thousands of sentences, we investigate the median value for the frequency or rank of words in first position in a sentence, compared with second position, and so on. We find that there is a frequency effect in English: the first element in a sentence has the highest frequency and last element in a sentence has the lowest frequency, with the middle of sentences having a more or less flat frequency profile. We also find that the overall shape of the frequency profile for sentences is rather consistent even when sentence length is taken into account.
Narrative viewpoint and subjective construal across languages
Authors: Lu Wei-lun 
Published: June 2020

AbstractThe present study explores the viewpointing function of word order inversion and associated stylistic strategies across languages, comparing English-Chinese multiple parallel texts as illustration. In particular, I investigate whether the cognitive strategy of inverting the word order to create a subjective construal is similar in both languages, to what extent, and if the languages differ, what systematic contingency plans there are. To answer the question, I examined selected excerpts with inversion written in English and their multiple translations in Mandarin Chinese, to see how the subjective construals in the English originals are rendered. I find that in addition to inversion, the English samples exhibit a zoom-in effect through use of punctuation, the participial clause, and an ad hoc schema of [some] – [X] with the middle three instantiations sharing an identical phonological schema. The identical phonological schema and the shared narrative viewpoint makes the three instantiations iconic. In comparison, the Chinese renditions employ the presentative construction and a focus particle to approximate the character-based viewpoint, but the zoom-in effect is not present in any of the Chinese versions. Another important difference is the generally longer iconic part in the Chinese versions, due to the productivity of four-character templates at the phonological pole in Mandarin Chinese.
Emphatic italics and the information structure of a prose text
Authors: Lukl Jiří 
Published: June 2020

Abstract
The emphatic function of italics has largely been ignored by linguists despite the value its understanding clearly has for written discourse studies. This paper aims to fill this gap. It is inspired by the types of relationship between the degrees of communicative dynamism and the degrees of prosodic prominence which the theory of functional sentence perspective has established for spoken language and applies them to written communication. At the same time, it maintains the distinction between the two modes of communication and suggests that it is only through covert prosody that any real parallels may be sought. The study uses two versions of a small corpus of written fiction. In the first version the original emphatic italics are preserved. In this instance the author’s intended covert prosody is partially accessible to the reader. The second version is one from which emphatic italics were removed. In this case the reader can only rely on their own covert prosody for interpretation. The versions were analyzed separately, and the analyses were then compared. Three relational types between the plain and italicized versions are identified: typographically amplifying, typographically revaluating, and typographically disambiguating. The paper concludes by suggesting some further avenues of research.
Role of social interaction abroad in the L2 acquisition of sociolinguistic variation
Authors: Denbaum Nofiya 
Published: June 2020

Abstract
Previous studies have concluded that second language learners (L2Ls) are capable of acquiring sociolinguistic variation. Since previous studies have found conflicting evidence on the effect that social interaction abroad has on the acquisition of sociolinguistic variation, the present study addresses this gap by including measures of this individual difference. Participants consist of students from a large US university who participate in a 6-week study abroad program in Santiago, Dominican Republic, compared to an at-home group. Participants completed a Study Abroad Social Interaction Questionnaire (SASIQ) and written contextualized tasks. The main purpose of the study is to examine whether students approach local norms of subject expression after studying abroad and what role social interaction abroad has in the acquisition process.
Proposing a tripartite intensifier system
Authors: Kanwit Matthew , Terán Virginia 
Published: June 2020

Abstract
Tripartite systems demonstrate how a dominant form coexists with other variants without any falling into disuse, as each occupies a particular space (Kapatsinski, 2009). Intensifiers reveal language change through rapid variability and recycling in popularity (Tagliamonte, 2008), as seen in variationist analyses of Spanish intensification via bien and muy (Brown & Cortés-Torres, 2013).
We consider an additional variant (i.e., re) and determine to what extent we can classify Argentinean intensifiers as a tripartite system. In a contextualized task which manipulated adjective quality, verb type, and animacy, 136 speakers from Buenos Aires and Tucumán selected their preferred intensifier. Mixed-effects regressions indicated re is constrained linguistically and socially, and that it occupies a different, specialized space from bien, while muy pervades cross-contextually.
Adequate contextual explicitation in translation
Authors: Hirsch Galia 
Published: June 2020

AbstractOn the face of it, it appears that the explicitation of contextual knowledge is consistent withToury’s (1995)norm of acceptability rather than his norm of adequacy. This is because this type of explicitation, which seeks to bridge the gap in readers’ contextual knowledge, enhances readability and is directed towards the target audience. However, in this article I argue that the use of this type of explicitation actually demonstrates an awareness of the importance of adhering to the source text, and may thus be aligned with adequacy norms. To support the argument, I show that this type of explicitation seems to be more prevalent than ever before, using as an example a recent translation of a story by O. Henry into Hebrew, in the context of Hebrew translated literature generally moving towards the norm of adequacy (Zoran 1990;Weissbrod 1992;Ben-Shahar 1994). This highlights the complexity of the relation between increased explicitness and the notions of adequacy and acceptability.
Triple knockdown of CDC37, HSP90‐alpha and HSP90‐beta diminishes extracellular vesicles‐driven malignancy events and macrophage M2 polarization in oral cancer
Authors: Ono Kisho , Sogawa Chiharu , Kawai Hotaka , Tran Manh Tien , Taha Eman A. , Lu Yanyin , Oo May Wathone , Okusha Yuka , Okamura Hirohiko , Ibaragi Soichiro , Takigawa Masaharu , Kozaki Ken‐Ichi , Nagatsuka Hitoshi , Sasaki Akira , Okamoto Kuniaki , Calderwood Stuart K. , Eguchi Takanori 
Published: June 2020

ABSTRACTEvidence has been accumulating to indicate that extracellular vesicles (EVs), including exosomes, released by cancer cells can foster tumour progression. The molecular chaperones – CDC37, HSP90α and HSP90β play key roles in cancer progression including epithelial‐mesenchymal transition (EMT), although their contribution to EVs‐mediated cell–cell communication in tumour microenvironment has not been thoroughly examined. Here we show that triple depletion of the chaperone trio attenuates numerous cancer malignancy events exerted through EV release. Metastatic oral cancer‐derived EVs (MEV) were enriched with HSP90α HSP90β and cancer‐initiating cell marker CD326/EpCAM. Depletion of these chaperones individually induced compensatory increases in the other chaperones, whereas triple siRNA targeting of these molecules markedly diminished the levels of the chaperone trio and attenuated EMT. MEV were potent agents in initiating EMT in normal epithelial cells, a process that was attenuated by the triple chaperone depletion. The migration, invasion, and in vitro tumour initiation of oral cancer cells were significantly promoted by MEV, while triple depletion of CDC37/HSP90α/β reversed these MEV‐driven malignancy events. In metastatic oral cancer patient‐derived tumours, HSP90β was significantly accumulated in infiltrating tumour‐associated macrophages (TAM) as compared to lower grade oral cancer cases. HSP90‐enriched MEV‐induced TAM polarization to an M2 phenotype, a transition known to support cancer progression, whereas the triple chaperone depletion attenuated this effect. Mechanistically, the triple chaperone depletion in metastatic oral cancer cells effectively reduced MEV transmission into macrophages. Hence, siRNA‐mediated knockdown of the chaperone trio (CDC37/HSP90α/HSP90β) could potentially be a novel therapeutic strategy to attenuate several EV‐driven malignancy events in the tumour microenvironment.AbbreviationsCDC37: cell division control 37; EMT: epithelial‐mesenchymal transmission; EV: extracellular vesicles; HNSCC: head and neck squamous cell carcinoma; HSP90: heat shock protein 90; TAM: tumour‐associated macrophage