bluuebunny/crossref_metadata_2025 huggingface dataset:
Tensile Fracture Behavior of 316L Austenitic Stainless Steel Manufactured by Hot Isostatic Pressing
Authors: Cooper A. J. , Brayshaw W. J. , Sherry A. H.
Published: February 2018

Herein we investigate how the oxygen content in hot isostatically pressed (HIP’d) 316L stainless steel affects the mechanical properties and tensile fracture behavior. This work follows on from previous studies, which aimed to understand the effect of oxygen content on the Charpy impact toughness of HIP’d steel. We expand on the work by performing room-temperature tensile testing on different heats of 316L stainless steel, which contain different levels of interstitial elements (carbon and nitrogen) as well as oxygen in the bulk material. Throughout the work we repeat the experiments on conventionally forged 316L steel as a reference material. The analysis of the work indicates that oxygen does not contribute to a measureable solution strengthening mechanism, as is the case with carbon and nitrogen in austenitic stainless steels (Werner in Mater Sci Eng A 101:93–98, 1988). Neither does oxygen, in the form of oxide inclusions, contribute to precipitation hardening due to the size and spacing of particles. However, the oxide particles do influence fracture behavior; fractography of the failed tension test specimens indicates that the average ductile dimple size is related to the oxygen content in the bulk material, the results of which support an on-going hypothesis relating oxygen content in HIP’d steels to their fracture mechanisms by providing additional sites for the initiation of ductile damage in the form of voids.
Frank Stinchfield Award: Identification of the At-risk Genotype for Development of Pseudotumors Around Metal-on-metal THAs
Authors: Kilb Brett K. J. , Kurmis Andrew P. , Parry Michael , Sherwood Karen , Keown Paul , Masri Bassam A. , Duncan Clive P. , Garbuz Donald S.
Published: February 2018

Background

Once touted as the future of hip arthroplasty, metal-on-metal (MoM) bearing surfaces have fallen sharply from favor with the emergence of a strong body of evidence demonstrating unacceptably high premature implant failure rates. The previously unpredictable development of adverse local tissue reactions (ALTRs) has been a substantive contributor to this. Although the underlying pathophysiology of these so-called “pseudotumors” is now well understood, the fundamental predisposing patient risk factors have remained elusive.

Questions/purposes

The aim of this research, as a clinical-genotype correlation analysis, was to identify specific alleles (genes) associated with the development of ALTRs in patients with in situ MoM THAs.

Methods

A case-control study of patients who received a large-head, primary MoM THA between 2005 and 2008 was performed with a minimum followup of 5 years. Twenty-six patients who had undergone revision of a primary MoM THA secondary to symptomatic ALTRs were recruited. The mean timeframe from primary MoM THA to symptomatic revision was 5.5 years (range, 1-10 years). Twenty-eight control subjects were randomly selected asymptomatic patients with no evidence of ALTRs on protocol-specific screening. Baseline demographics and high-resolution genotype (human leukocyte antigen [HLA] Class II) were collected for all patients. Cohorts were similar with respect to age at the time of primary MoM THA (mean, 54.8 versus 54.9 years, p = 0.95) and serum cobalt (mean, 5.5 versus 8.5 μg/L, p = 0.09) and chromium concentrations (mean, 2.9 versus 4.2 μg/L, p = 0.27). The association between genotype and revision surgery secondary to ALTRs was determined with gender as a covariate.

Results

The prevalence of the risk genotype was 30% (16 of 54) among the entire cohort. Adjusting for sex, the odds of revision were 6.1 times greater among patients with the risk genotype present than among patients without (95% confidence interval [CI], 1.5-25.4; p = 0.01). Among females, the specificity of the risk genotype was 1.0 (95% CIexact, 0.5-1.0; pexact= 0.03), and for males, it was 0.8 (95% CIexact, 0.6-0.9; pexact< 0.01).

Conclusions

The findings of this study suggest that, among patients with a primary MoM THA, allelic variation within the HLA Class II loci may be a strong, independent risk factor associated with the need for subsequent revision surgery secondary to pseudotumor formation.

Clinical Relevance

Given the hypothesis-generating nature of this novel undertaking, confirmatory prospective clinical studies are required to further elucidate this correlation and to explore the clinical utility of targeted genetic screening in this specific population. This research may, however, represent a key missing piece in the puzzle that is metal ion-induced pseudotumor formation.
English vowel perception by Polish advanced learners of English
Authors: Balas Anna
Published: February 2018

This article examines English vowel perception by advanced Polish learners of English in a formal classroom setting (i.e., they learnt English as a foreign language in school while living in Poland). The stimuli included 11 English noncewords in bilabial (/bVb/), alveolar (/dVd/) and velar (/gVg/) contexts. The participants, 35 first-year English majors, were examined during the performance of three tasks with English vowels: a categorial discrimination oddity task, an L1 assimilation task (categorization and goodness rating) and a task involving rating the (dis-)similarities between pairs of English vowels. The results showed a variety of assimilation types according to the Perceptual Assimilation Model (PAM) and the expected performance in a discrimination task. The more difficult it was to discriminate between two given vowels, the more similar these vowels were judged to be. Vowel contrasts involving height distinctions were easier to discriminate than vowel contrasts with tongue advancement distinctions. The results also revealed that the place of articulation of neighboring consonants had little effect on the perceptibility of the tested English vowels, unlike in the case of lower-proficiency learners. Unlike previous results for naïve listeners, the present results for advanced learners showed no adherence to the principles of the Natural Referent Vowel framework. Generally, the perception of English vowels by these Polish advanced learners of English conformed with PAM's predictions, but differed from vowel perception by naïve listeners and lower-proficiency learners.
Swift and Low-Cost Surge in Chemical Threat Response: Is It Possible? The Experience of a French Hospital
Authors: Brizio Albert , Hubert Jean-Christophe , Hennequin Brigitte , Bouchez Jeremy , Kouka Marie-Clément
Published: February 2018

In 2016 France hosted the European football championship. In a context of an increased terrorist threat, Chemical, Bacteriological, Radiological, Nuclear (CBRN) attacks were considered possible. Three days prior to the beginning of the event, the Health Authorities required that a medium sized hospital close to a major potential target, prepare a chemical decontamination centre. Despite a low level of preparedness, little external help, and very few extra resources, an efficient decontamination chain (all premises necessary for the management of contaminated victims: from the entrance gate to the post-decontamination dressing cabins) was set up in 15 days (12 days after the unrealistic deadline). Numerous practical measures allowed three persons in CBRN personal protective equipment (PPE) to manage the whole chain, providing a maximum flow of 24 persons/hour. Volunteers were trained in PPE dressing, undressing and in decontamination procedures. This experience, offers a novel paradigm in managing chemical decontamination, in terms of attitude, and with adaptations to overcome practical constraints. It demonstrates that it is possible to set up a decontamination chain rapidly at very low cost. This provides an attractive option for less advanced countries and in humanitarian contexts. Some additional refinements, enhancements may be considered to further improve results. (Disaster Med Public Health Preparedness. 2018;12:649–656)
“The War, like the Wicked Wand of a Wizard, Strikes Me and Carry Away All that I Have Loved:” Soldiers’ Family Lives and Petition Writing in Ijebu, Southwestern Nigeria, 1943–1945
Authors: Coates Oliver
Published: February 2018

The social isolation of the African soldiery is a recurrent assumption in the historiography of the Second World War in Anglophone Africa; such factors as the experience of Hausa soldiers within a cohesive barracks community, a strong sense of warrior identity, and few ties to civilian life are too often generalized into an account of the soldiery as necessarily isolated. Focusing on Ijebu in southwestern Nigeria, an area with little history of colonial military service prior to the Second World War, this paper will argue that far from being deeply isolated, Ijebu soldiers and their families strove desperately to maintain customary obligations during the men’s military service in South Asia and the Middle East in 1944 and 1945. By examining soldiers’ petitions to the Ijebu District Officer, as well as petitions from their wives, brothers, and parents, we will see that soldiers were bound by a powerful sense of obligation to their extended family not only in terms of financial support, but also in relation to labor, security, administration, and redistribution. Contextualizing these sources in terms of the ethnography of customary obligations in southwestern Nigeria, this paper will argue that neither soldiers nor their families primarily regarded these men as martial professionals, but instead perceived soldiering as a subordinate and secondary concern to family and economic commitments, as expressed through customary obligations. Although it likely differs from the experience of soldiers from supposedly “martial” groups, the experience of the Ijebu sheds light on the military service of the newer groups recruited during the war.
Cost-Effectiveness of Competing Treatment Strategies for Clostridium difficile Infection: A Systematic Review
Authors: Le Phuc , Nghiem Van T. , Mullen Patricia Dolan , Deshpande Abhishek
Published: February 2018

BACKGROUND

Clostridium difficile infection (CDI) presents a substantial economic burden and is associated with significant morbidity. While multiple treatment strategies have been evaluated, a cost-effective management strategy remains unclear.

OBJECTIVE

We conducted a systematic review to assess cost-effectiveness analyses of CDI treatment and to summarize key issues for clinicians and policy makers to consider.

METHODS

We searched PubMed and 5 other databases from inception to August 2016. These searches were not limited by study design or language of publication. Two reviewers independently screened the literature, abstracted data, and assessed methodological quality using the Drummond and Jefferson checklist. We extracted data on study characteristics, type of CDI, treatment characteristics, and model structure and inputs.

RESULTS

We included 14 studies, and 13 of these were from high-income countries. More than 90% of these studies were deemed moderate-to-high or high quality. Overall, 6 studies used a decision-tree model and 7 studies used a Markov model. Cost of therapy, time horizon, treatment cure rates, and recurrence rates were common influential factors in the study results. For initial CDI, fidaxomicin was a more cost-effective therapy than metronidazole or vancomycin in 2 of 3 studies. For severe initial CDI, 2 of 3 studies found fidaxomicin to be the most cost-effective therapy. For recurrent CDI, fidaxomicin was cost-effective in 3 of 5 studies, while fecal microbiota transplantation (FMT) by colonoscopy was consistently cost-effective in 4 of 4 studies.

CONCLUSIONS

The cost-effectiveness of fidaxomicin compared with other pharmacologic therapies was not definitive for either initial or recurrent CDI. Despite its high cost, FMT by colonoscopy may be a cost-effective therapy for recurrent CDI. A consensus on model design and assumptions are necessary for future comparison of CDI treatment.

Infect Control Hosp Epidemiol 2018;39:412–424
Early–middle Holocene ecological change and its influence on human subsistence strategies in the Luoyang Basin, north-central China
Authors: Zhang Junna , Xia Zhengkai , Zhang Xiaohu , Storozum Michael J. , Huang Xiaozhong , Han Jianye , Xu Hong , Zhao Haitao , Cui Yifu , Dodson John , Dong Guanghui
Published: February 2018

In north-central China, subsistence practices transitioned from hunting and gathering to millet-based agriculture between the early and middle Holocene. To better understand how ancient environmental changes influenced this shift in subsistence strategies and human activities at regional to local levels, we conducted palynological and lithologic analyses on radiocarbon-dated sediment cores from the Luoyang Basin, western Henan Province. Our palynological results suggest that vegetation shifted from broad-leaved deciduous forest (9230–8850 cal yr BP) to steppe-meadow vegetation (8850–7550 cal yr BP), and then to steppe with sparse trees (7550–6920 cal yr BP). Lithologic analyses also indicate that the stabilization of the Luoyang Basin’s floodplain after ~8370 cal yr BP might have attracted people to move into the basin, promoting the emergence of millet-based agriculture during the Peiligang culture period (8500–7000 cal yr BP). Once agricultural practices emerged, the climatic optimum after ~7550 cal yr BP likely facilitated the expansion of the Yangshao culture (7000–5000 cal yr BP) in north-central China. As agriculture intensified, pollen taxa related to human disturbance, such asUrtica, increased in abundance.
Millennial-scale decline in coho salmon abundance since the middle Holocene in a coastal Oregon watershed, USA
Authors: Gavin Daniel G. , Kusler Jennifer E. , Finney Bruce P.
Published: February 2018

The population size of anadromous salmon in the Pacific Northwest is strongly influenced by decadal variation in watershed and oceanographic conditions and therefore should also be influenced by larger magnitude millennial-scale variations in these conditions. We studied δ15N of bulk organic matter in lake sediment from Woahink Lake, Oregon, as a proxy of marine-derived nutrients (MDN) from spawning coho salmon. We compared this site to a control lake with a natural barrier to salmon migration. From 7.5 to 5.4 ka, a dune was emplaced, breached, and emplaced again, forming Woahink Lake in a former estuary. δ15N decreased steadily since 5.4 ka at Woahink but not at the control lake. δ15N reached a minimum just prior to anthropogenic nutrient loading, which caused an increase in δ15N, thus precluding a comparison with the historical decline in salmon abundance. A mixing model of lake-water nitrate, developed to explore alternate scenarios for the observed range of δ15N, could not explain these results without invoking MDN input from at least several hundred salmon annually. Our results show a previously unreported pattern of a millennial-scale decline in salmon that has plausible linkages to parallel changes in ocean circulation and productivity.
Marx and World History
Authors: Krätke Michael R.
Published: February 2018

In 1881–1882, Marx undertook extensive historical studies, covering a large part of what was then known as “world history”. The four large notebooks with excerpts from the works of (mainly) two leading historian of his time, Schlosser and Botta, have remained largely unpublished. In this article, Marx’s last studies of the course of world history are contextualized: Marx’s previous historical studies and his ongoing, but unfinished work on the critique of political economy. The range and scope of his notes is astoundingly broad, going far beyond European history and actually covering many other parts of the world. Marx’s focus in these studies supports the interpretation offered in the article: that the author of “Capital” was fascinated by the long process of the making of the modern states and the European states system, one of the crucial prerequisites of the rise of modern capitalism in Europe.
The Judiciary within the State: Governance and Cohesion of the Judiciary
Authors: Lord Thomas of Cwmgiedd
Published: February 2018

I am particularly grateful to be accorded the honour and privilege of giving this year's Lionel Cohen Lecture as it enables me to examine the position of the judiciary within the state.
Why underlying representations?
Authors: HYMAN LARRY M.
Published: February 2018

Phonology is a rapidly changing and increasingly varied field, having traveled quite some distance from its original structuralist and generative underpinnings. In this overview I address the status of underlying representations (URs) in phonology, which have been rejected by a number of researchers working in different frameworks. After briefly discussing the current state of phonology, I survey the arguments in favor of vs. against URs, considering recent surface-oriented critiques and alternatives. I contrast three straightforward abstract tonal analyses against the potential arguments which accuse URs of being (i) wrong, (ii) redundant, (iii) indeterminate, (iv) insufficient, or (v) uninteresting. Identifying two distinct goals in linguistics which I refer to as determining ‘what’s in the head?’ vs. ‘what’s in the language?’, I suggest, responding to some rather strong opinions to the contrary, that URs are an indispensable and welcome tool offering important insights into the typology of phonological systems, if not beyond.
New and emerging uses of CRISPR/Cas9 to genetically manipulate apicomplexan parasites
Authors: Di Cristina Manlio , Carruthers Vern B.
Published: February 2018

Although the application of CRISPR/Cas9 genome engineering approaches was first reported in apicomplexan parasites only 3 years ago, this technology has rapidly become an essential component of research on apicomplexan parasites. This review briefly describes the history of CRISPR/Cas9 and the principles behind its use along with documenting its implementation in apicomplexan parasites, especially Plasmodium spp. and Toxoplasma gondii. We also discuss the recent use of CRISPR/Cas9 for whole genome screening of gene knockout mutants in T. gondii and highlight its use for seminal genetic manipulations of Cryptosporidium spp. Finally, we consider new variations of CRISPR/Cas9 that have yet to be implemented in apicomplexans. Whereas CRISPR/Cas9 has already accelerated rapid interrogation of gene function in apicomplexans, the full potential of this technology is yet to be realized as new variations and innovations are integrated into the field.
Functions of Turkish evidentials in early child–caregiver interactions: a growth curve analysis of longitudinal data
Authors: UZUNDAĞ Berna A. , TAŞÇI Süleyman S. , KÜNTAY Aylin C. , AKSU-KOÇ Ayhan
Published: February 2018

In languages with evidential marking, utterances consist of an informational content and a specification of the mode of access to that information. In this first longitudinal study investigating the acquisition of the Turkish evidential marker −mIşin naturalistic child–caregiver interactions, we examined six children between 8 and 36 months of age. We charted individual differences in child and caregiver speech over time by conducting growth curve analyses. Children followed a similar course of acquisition in terms of the proportion of the marker in overall speech. However, children exhibited differences with respect to the order of emergence of different evidential functions (e.g., inference, hearsay), where each child showed a unique pattern irrespective of the frequency in caregiver input. Nonfactual use of the marker was very frequent in child and caregiver speech, where high-SES caregivers mostly produced the marker during story-telling and pretend play, and low-SES caregivers for regulating the child's behavior.
Archipelagos of learning: environmental education on islands
Authors: SELBY DAVID , KAGAWA FUMIYO
Published: February 2018

This article appreciatively reviews environmental education practice on islands through the lens of four key strands of environmental education discourse: biodiversity, conservation and science-framed education; place-based, indigenized and bioregional education; climate change and disaster risk reduction education; and education for sustainable development. Arising from these strands and their interface, six questions are asked of the examples of island practice reviewed. A final section asks what is distinctive about environmental education on islands and comes up with five principal findings. First, it is observed that environmental education initiatives on islands are markedly eclectic in their rich blending of practice from within the different strands. Second, it is noted that environmental education practice on different islands, especially in the Pacific, is marked by a return to indigenous, community-based learning. Third, the emergence of a distinctive pedagogy is remarked upon, especially the greater weighting given to relational, socio-affective and action-orientated learning. Fourth, the paucity of inter-island cosmopolitan dialogue is noted and questions are asked about how to ensure island learners steeped in learning about place can be brought to connect with the global environmental problematic. Fifth, the frequency of cross-curricular, interdisciplinary, even trans-disciplinary framing of environmental education initiatives is identified as bringing distinctiveness to island practice.
Experience Machines, Conflicting Intuitions and the Bipartite Characterization of Well-being
Authors: STEVENSON CHAD M.
Published: February 2018

While Nozick and his sympathizers assume there is a widespread anti-hedonist intuition to prefer reality to an experience machine, hedonists have marshalled empirical evidence that shows such an assumption to be unfounded. Results of several experience machine variants indicate there is no widespread anti-hedonist intuition. From these findings, hedonists claim Nozick's argument fails as an objection to hedonism. This article suggests the argument surrounding experience machines has been misconceived. Rather than eliciting intuitions about what is prudentially valuable, these intuitive judgements are instead calculations about prudential pay-offs and trade-offs. This position can help explain the divergence of intuitions people have about experience machines.
Haemodynamic consequences following closure of an Abernethy malformation in a patient following a total cavopulmonary shunt
Authors: Sasikumar Deepa , Sasidharan Bijulal , Ayyappan Anoop
Published: February 2018

A 17-year-old girl with situs ambiguous, hypoplastic right ventricle with a large ventricular septal defect, and severe pulmonary stenosis had undergone Kawashima operation 10 years back. She had significant desaturation because of a large Abernethy malformation, with reverse shunting from the inferior caval vein to the portal vein. It was closed with a vascular plug, with improvement in oxygen saturation. She developed extensive inferior caval vein thrombus following the procedure, which was managed conservatively by anti-coagulation.
Inferring the atmospheric duct from radar sea clutter using the improved artificial bee colony algorithm
Authors: Yang Chao , Guo Lixin
Published: February 2018

In this paper, an orthogonal crossover artificial bee colony (OCABC) algorithm based on orthogonal experimental design is presented and applied to infer the marine atmospheric duct using the refractivity from clutter technique, and the radar sea clutter power is simulated by the commonly used parabolic equation method. In order to test the accuracy of the OCABC algorithm, the measured data and the simulated clutter power with different noise levels are, respectively, utilized to estimate the evaporation duct and surface duct. The estimation results obtained by the proposed algorithm are also compared with those of the comprehensive learning particle swarm optimizer and the artificial bee colony algorithm combined with opposition-based learning and global best search equation. The comparison results demonstrate that the performance of proposed algorithm is better than those of the compared algorithms for the marine atmospheric duct estimation.
Home-based exercise for elderly patients with intermittent claudication limited by osteoarticular disorders – feasibility and effectiveness of a low-intensity programme
Authors: Lamberti Nicola , Straudi Sofia , Lissia Efisio , Cavazzini Lorenza , Buja Sergio , Manfredini Roberto , Basaglia Nino , Manfredini Fabio
Published: February 2018

Abstract. Background: Peripheral arterial disease (PAD) is a common cardiovascular pathology affecting mobility in elderly. Osteoarticular diseases (ODs), responsible for functional limitations and confounding leg symptoms, may interfere with exercise therapy. This study evaluates the feasibility and effectiveness of a structured home-based exercise programme on rehabilitative outcomes in a cohort of elderly PAD patients with and without coexisting ODs. Patients and methods: Patients were enrolled from 2002 to 2016 in an exercise programme prescribed and controlled at the hospital and based on two daily 10-minute home walking sessions below the self-selected speed. The presence and localization of ODs at baseline were derived from consultation of medical documents. The ankle-brachial index and functional outcomes, defined as speed at the onset of claudication and attainable maximal speed by an incremental treadmill test, were assessed at baseline and discharge. Feasibility was determined according to dropout rate, number of visits, duration of the programme, and adherence. Results: A total of 1,251 PAD patients were enrolled (931 men; 71 ± 9 years; 0.63 ± 0.19 ankle-brachial index). Eight hundred sixty-four patients were free of ODs (ODfreePAD, 69 %), whereas 387 were affected by ODs (ODPAD, 31 %), predominantly located in the spine (72 %). In the logistic regression models, the presence of ODs was associated with female sex, overweight, sedentary and/or driving professions. At discharge, ODPADand ODfreePADdid not differ in dropout rates (12 % each), programme duration (378 ± 241 vs. 390 ± 260 days), number of visits (7 ± 3 each), and adherence (80 % each). Similar improvements for ODPADand ODfreePADwere observed for the ankle-brachial index (0.06 ± 0.12 each), the speed at onset of claudication (0.7 ± 0.7 vs. 0.7 ± 0.8 kmh-1; p = 0.70), and maximal speed (0.4 ± 0.6 vs. 0.4 ± 0.6 kmh-1; p = 0.77). Conclusions: Equally satisfactory rehabilitative outcomes were observed in elderly patients with claudication limited by ODs who completed a well-tolerated, low-impact structured exercise programme.
Identification of a novel microRNA-mRNA regulatory biomodule in human prostate cancer
Authors: Zhang Yanqiong , Jiang Funeng , He Huichan , Ye Jianheng , Mao Xia , Guo Qiuyan , Wu Shu-lin , Zhong Weide , Wu Chin-Lee , Lin Na
Published: February 2018

Our recent study identified a list of differentially expressed microRNAs (miRNAs) in human prostate cancer (PCa) tissues compared to adjacent benign prostate tissues. In the current study, to identify the crucial miRNA–mRNA regulatory biomodule involved into prostate carcinogenesis based on the previous miRNA expression profile in PCa, we proposed an integrated systematic approach which combined miRNA-mediated gene expression regulatory network analysis, experimental validations in vitro and in vivo, as well as clinical significance evaluation. As a result, the CCND1-RNASEL-CDKN1A-TP73-MDM2-UBE2I axis was identified as a bottleneck in the miRNA-mediated gene expression regulatory network of PCa according to network topological analysis. The direct binding relationship between TP73 and PCa downregulated miR-193a-5p, and the direct binding relationship between UBE2I and PCa upregulated miR-188-5p were both experimentally validated. In addition, miR-193a-5p had a more significant regulatory effect on the tumor promoter isoform of TP73-deltaNp73 than on the tumor suppressive isoform of TP73-TAp73. Importantly, the deregulation of either the miR-193a-5p-TP73 or miR-188-5p-UBE2I axes was significantly associated with aggressive progression and poor prognosis in PCa patients. Gain- and loss-of-function experiments showed that miR-193a-5p efficiently inhibited in vitro PCa cell proliferation, migration, and invasion, and in vivo tumor growth, and markedly induced PCa cell apoptosis via regulating TP73 with a corresponding suppression of the CCND1-RNASEL-CDKN1A-MDM2 axis. In contrast, miR-188-5p exerted its tumor promoter roles through targeting UBE2I with a subsequent activation of the CCND1-RNASEL-CDKN1A-MDM2 axis. Taken together, this integrated analysis revealed the potential roles of the miR-193a-5p/TP73 and miR-188-5p/UBE2i negative regulation pairs in PCa. In addition to the significant clinical relevance, miR-193a-5p- and miR-188-5p-regulated CCND1-RNASEL-CDKN1A-TP73-MDM2-UBE2I signaling may be a novel regulatory biomodule in prostate carcinogenesis.
Long glucocorticoid-induced leucine zipper regulates human thyroid cancer cell proliferation
Authors: Ayroldi Emira , Petrillo Maria Grazia , Marchetti Maria Cristina , Cannarile Lorenza , Ronchetti Simona , Ricci Erika , Cari Luigi , Avenia Nicola , Moretti Sonia , Puxeddu Efisio , Riccardi Carlo
Published: February 2018

Long glucocorticoid-induced leucine zipper (L-GILZ) has recently been implicated in cancer cell proliferation. Here, we investigated its role in human thyroid cancer cells. L-GILZ protein was highly expressed in well-differentiated cancer cells from thyroid cancer patients and differentiated thyroid cancer cell lines, but poorly expressed in anaplastic tumors. A fusion protein containing L-GILZ, when overexpressed in an L-GILZ-deficient 8505C cell line derived from undifferentiated human thyroid cancer tissue, inhibited cellular proliferation in vitro. In addition, when this protein was injected into nude mice, in which cells from line 8505C had been transplanted, xenograft growth was reduced. Since the mitogen-activated protein kinase (MAPK) pathway is frequently hyperactivated in thyroid cancer cells as a result of the BRAFV600E or Ras mutation, we sought to further investigate the role of L-GILZ in the MAPK pathway. To this end, we analyzed L-GILZ expression and function in cells treated with MAPK inhibitors. We used 8505C cells, which have the BRAFV600E mutation, or the CAL-62 cell line, which harbors a Ras mutation. The cells were treated with the BRAF-specific drug vemurafenib (PLX4032) or the MEK1/2 inhibitor, U0126, respectively. Treatment with these agents inhibited MAPK activation, reduced cell proliferation, and upregulated L-GILZ expression. L-GILZ silencing reversed the antiproliferative activity of the MAPK inhibitors, consistent with an antiproliferative role. Treatment with MAPK inhibitors led to the phosphorylation of the cAMP/response element-binding protein (CREB), and active CREB bound to the L-GILZ promoter, contributing to its transcription. We suggest that the CREB signaling pathway, frequently deregulated in thyroid tumors, is involved in L-GILZ upregulation and that L-GILZ regulates thyroid cancer cell proliferation, which may have potential in cancer treatment.
IL-32 gamma reduces lung tumor development through upregulation of TIMP-3 overexpression and hypomethylation
Authors: Yun Jaesuk , Park Mi Hee , Son Dong Ju , Nam Kyung Tak , Moon Dae Bong , Ju Jung Heun , Hwang Ok Kyung , Choi Jeong Soon , Kim Tae Hoon , Jung Young Suk , Hwang Dae Yeon , Han Sang Bae , Yoon Do-Young , Hong Jin Tae
Published: February 2018

The low expression of tissue inhibitor of metalloproteinase 3 (TIMP-3) is important in inflammatory responses. Therefore, inhibition of TIMP-3 may promote tumor development. Our study showed that expression of TIMP-3 was elevated in lL-32γ mice lung tissues. In this study, we investigated whether IL-32γ mice inhibited lung tumor development through overexpression of TIMP-3 and its methylation. To explore the possible underlying mechanism, lung cancer cells were transfected with IL-32γ cDNA plasmid. A marked increase in TIMP-3 expression was caused by promoter methylation. Mechanistic studies indicated that TIMP-3 overexpression reduced NF-κB activity, which led to cell growth inhibition in IL-32γ transfected lung cancer cells. We also showed that IL-32γ inhibits expression of DNA (cytosine-5-)-methyltransferase 1 (DNMT1). Moreover, IL-32γ inhibits the binding of DNMT1 to TIMP-3 promoter, but this effect was reversed by the treatment of DNA methyltransferase inhibitor (5-Aza-CdR) and NF-κB inhibitor (PS1145), suggesting that a marked increase in TIMP-3 expression was caused by inhibition of promoter hypermethylation via decreased DNMT1 expression through the NF-κB pathway. In an in vivo carcinogen induced lung tumor model, tumor growth was inhibited in IL-32γ overexpressed mice with elevated TIMP-3 expression and hypomethylation accompanied with reduced NF-κB activity. Moreover, in the lung cancer patient tissue, the expression of IL-32 and TIMP-3 was dramatically decreased at a grade-dependent manner compared to normal lung tissue. In summary, IL-32γ may increase TIMP-3 expression via hypomethylation through inactivation of NF-κB activity, and thereby reduce lung tumor growth.
Attosecond recorder of the polarization state of light
Authors: Jiménez-Galán Álvaro , Dixit Gopal , Patchkovskii Serguei , Smirnova Olga , Morales Felipe , Ivanov Misha
Published: February 2018

High harmonic generation in multi-color laser fields opens the opportunity of generating isolated attosecond pulses with high ellipticity. Such pulses hold the potential for time-resolving chiral electronic, magnetization, and spin dynamics at their natural timescale. However, this potential cannot be realized without characterizing the exact polarization state of light on the attosecond timescale. Here we propose and numerically demonstrate a complete solution of this problem. Our solution exploits the extrinsic two-dimensional chirality induced in an atom interacting with the chiral attosecond pulse and a linearly polarized infrared probe. The resulting asymmetry in the photoelectron spectra allows to reconstruct the complete polarization state of the attosecond pulse, including its possible time dependence. The challenging problem of distinguishing circularly polarized, partially polarized, or unpolarized pulses in the extreme ultraviolet range is also resolved. We expect this approach to become the core ingredient for attosecond measurements of chiral-sensitive processes in gas and condensed phase.
Frequency multiplexing for quasi-deterministic heralded single-photon sources
Authors: Joshi Chaitali , Farsi Alessandro , Clemmen Stéphane , Ramelow Sven , Gaeta Alexander L.
Published: February 2018

Parametric single-photon sources are well suited for large-scale quantum networks due to their potential for photonic integration. Active multiplexing of photons can overcome the intrinsically probabilistic nature of these sources, resulting in near-deterministic operation. However, previous implementations using spatial and temporal multiplexing scale unfavorably due to rapidly increasing switching losses. Here, we break this limitation via frequency multiplexing in which switching losses remain fixed irrespective of the number of multiplexed modes. We use low-noise optical frequency conversion for efficient frequency switching and demonstrate multiplexing of three modes. We achieve a generation rate of 4.6 × 104 photons per second with an ultra-low g(2)(0) = 0.07 indicating high single-photon purity. Our scalable, all-fiber multiplexing system has a total loss of just 1.3 dB, such that the 4.8 dB multiplexing enhancement markedly overcomes switching loss. Our approach offers a promising path to creating a deterministic photon source on an integrated chip-based platform.
Evidence that DNA polymerase δ contributes to initiating leading strand DNA replication in Saccharomyces cerevisiae
Authors: Garbacz Marta A. , Lujan Scott A. , Burkholder Adam B. , Cox Phillip B. , Wu Qiuqin , Zhou Zhi-Xiong , Haber James E. , Kunkel Thomas A.
Published: February 2018

To investigate nuclear DNA replication enzymology in vivo, we have studied Saccharomyces cerevisiae strains containing a pol2-16 mutation that inactivates the catalytic activities of DNA polymerase ε (Pol ε). Although pol2-16 mutants survive, they present very tiny spore colonies, increased doubling time, larger than normal cells, aberrant nuclei, and rapid acquisition of suppressor mutations. These phenotypes reveal a severe growth defect that is distinct from that of strains that lack only Pol ε proofreading (pol2-4), consistent with the idea that Pol ε is the major leading-strand polymerase used for unstressed DNA replication. Ribonucleotides are incorporated into the pol2-16 genome in patterns consistent with leading-strand replication by Pol δ when Pol ε is absent. More importantly, ribonucleotide distributions at replication origins suggest that in strains encoding all three replicases, Pol δ contributes to initiation of leading-strand replication. We describe two possible models.
On the relative motions of long-lived Pacific mantle plumes
Authors: Konrad Kevin , Koppers Anthony A. P. , Steinberger Bernhard , Finlayson Valerie A. , Konter Jasper G. , Jackson Matthew G.
Published: February 2018

Mantle plumes upwelling beneath moving tectonic plates generate age-progressive chains of volcanos (hotspot chains) used to reconstruct plate motion. However, these hotspots appear to move relative to each other, implying that plumes are not laterally fixed. The lack of age constraints on long-lived, coeval hotspot chains hinders attempts to reconstruct plate motion and quantify relative plume motions. Here we provide 40Ar/39Ar ages for a newly identified long-lived mantle plume, which formed the Rurutu hotspot chain. By comparing the inter-hotspot distances between three Pacific hotspots, we show that Hawaii is unique in its strong, rapid southward motion from 60 to 50 Myrs ago, consistent with paleomagnetic observations. Conversely, the Rurutu and Louisville chains show little motion. Current geodynamic plume motion models can reproduce the first-order motions for these plumes, but only when each plume is rooted in the lowermost mantle.
Publisher Correction: Direct quantum process tomography via measuring sequential weak values of incompatible observables
Authors: Kim Yosep , Kim Yong-Su , Lee Sang-Yun , Han Sang-Wook , Moon Sung , Kim Yoon-Ho , Cho Young-Wook
Published: February 2018

In the original version of this Article, the penultimate sentence of the second paragraph of the “Schematic and theory” section of the Results originally incorrectly read as “For instance, choosing θA = π/4, 0, −π/8 and π/8 rotates the bases |0>, |1>, |+>, and |−> into |1>, thereby implementing the observableÂ=|0><0|, |1><1|, |+><+| and, respectively.” In the corrected version, “|−><−|” has been added before “, respectively”. This error has been corrected in both the PDF and HTML versions of the Article.
Author Correction: Muscle pathology from stochastic low level DUX4 expression in an FSHD mouse model
Authors: Bosnakovski Darko , Chan Sunny S. K. , Recht Olivia O. , Hartweck Lynn M. , Gustafson Collin J. , Athman Laura L. , Lowe Dawn A. , Kyba Michael
Published: February 2018

In the originally published version of this Article, an incorrect grant number, RO1 NS083549, was acknowledged. The correct grant number is RO1 AR055685. This error has now been corrected in both the PDF and HTML versions of the Article.
Sugar based N,N′-didodecyl-N,N′digluconamideethylenediamine gemini surfactant as corrosion inhibitor for mild steel in 3.5% NaCl solution-effect of synergistic KI additive
Authors: Aslam Ruby , Mobin Mohammad , Aslam Jeenat , Lgaz Hassane
Published: February 2018

The inhibitory behaviour of non-ionic sugar basedN,N′-didodecyl-N,N′-digluconamideethylenediamine gemini surfactant, designated as Glu(12)-2-Glu(12) on mild steel (MS) corrosion in 3.5% NaCl at 30–60 °C was explored using weight loss, PDP, EIS and SEM/EDAX/AFM techniques. The compound inhibited the corrosion of mild steel in 3.5% NaCl and the extent of inhibition was dependent on concentration and temperature. The inhibiting action of Glu(12)-2-Glu(12) is synergistically enhanced on addition of potassium iodide (KI) at all concentrations and temperatures. The inhibiting formulation comprising of 2.5 × 10−3mM of Glu(12)-2-Glu(12) and 10 mM of KI exhibits an inhibition efficiency of 96.9% at 60 °C. Quantum chemical calculations and MD simulation were applied to analyze the experimental data and elucidate the adsorption behaviour and inhibition mechanism of inhibitors. MD simulation showed a nearly parallel or flat disposition for Glu(12)-2-Glu(12) molecules on the MS surface providing larger blocking area to prevent the metal surface from corrosion.
Creating a 3D microbial and chemical snapshot of a human habitat
Authors: Kapono Clifford A. , Morton James T. , Bouslimani Amina , Melnik Alexey V. , Orlinsky Kayla , Knaan Tal Luzzatto , Garg Neha , Vázquez-Baeza Yoshiki , Protsyuk Ivan , Janssen Stefan , Zhu Qiyun , Alexandrov Theodore , Smarr Larry , Knight Rob , Dorrestein Pieter C.
Published: February 2018

One of the goals of forensic science is to identify individuals and their lifestyle by analyzing the trace signatures left behind in built environments. Here, microbiome and metabolomic methods were used to see how its occupants used an office and to also gain insights into the lifestyle characteristics such as diet, medications, and personal care products of the occupants. 3D molecular cartography, a molecular visualization technology, was used in combination with mass spectrometry and microbial inventories to highlight human-environmental interactions. Molecular signatures were correlated with the individuals as well as their interactions with this indoor environment. There are person-specific chemical and microbial signatures associated with this environment that directly relate who had touched objects such as computers, computer mice, cell phones, desk phone, table or desks. By combining molecular and microbial investigation forensic strategies, this study offers novel insights to investigators who value the reconstructing of human lifestyle and characterization of human environmental interaction.
Environmental and anthropogenic factors affecting the increasing occurrence of shark-human interactions around a fast-developing Indian Ocean island
Authors: Lagabrielle Erwann , Allibert Agathe , Kiszka Jeremy J. , Loiseau Nicolas , Kilfoil James P. , Lemahieu Anne
Published: February 2018

Understanding the environmental drivers of interactions between predators and humans is critical for public safety and management purposes. In the marine environment, this issue is exemplified by shark-human interactions. The annual shark bite incidence rate (SBIR) in La Réunion (Indian Ocean) is among the highest in the world (up to 1 event per 24,000 hours of surfing) and has experienced a 23-fold increase over the 2005–2016 period. Since 1988, 86% of shark bite events on surfers involved ocean-users off the leeward coast, where 96% of surfing activities took place. We modeled the SBIR as a function of environmental variables, including benthic substrate, sea temperature and period of day. The SBIR peaked in winter, during the afternoon and dramatically increased on coral substrate since the mid-2000s. Seasonal patterns of increasing SBIR followed similar fluctuations of large coastal shark occurrences (particularly the bull sharkCarcharhinus leucas), consistent with the hypothesis that higher shark presence may result in an increasing likelihood of shark bite events. Potential contributing factors and adaptation of ocean-users to the increasing shark bite hazard are discussed. This interdisciplinary research contributes to a better understanding of shark-human interactions. The modeling method is relevant for wildlife hazard management in general.
Synchrony and social connection in immersive Virtual Reality
Authors: Tarr B. , Slater M. , Cohen E.
Published: February 2018

Synchronising movements in time with others can have significant positive effects on affiliative attitudes and behaviors. To explore the generalizability of synchrony effects, and to eliminate confounds of suggestion, competence and shared intention typical of standard laboratory and field experiments, we used an Immersive Virtual Reality (VR) environment. Participants, represented as virtual humans, took part in a joint movement activity with two other programmed virtual humans. The timings of the co-participant characters’ movements were covertly manipulated to achieve synchrony or non-synchrony with the focal participant. Participants in the synchrony condition reported significantly greater social closeness to their virtual co-participants than those in the non-synchrony condition. Results indicate that synchrony in joint action causes positive social effects and that these effects are robust in a VR setting. The research can potentially inform the development of VR interventions for social and psychological wellbeing.
Nano-scale mechanisms explain the stiffening and strengthening of ligament tissue with increasing strain rate
Authors: Karunaratne Angelo , Li Simin , Bull Anthony M. J.
Published: February 2018

Ligament failure is a major societal burden causing disability and pain. Failure is caused by trauma at high loading rates. At the macroscopic level increasing strain rates cause an increase in failure stress and modulus, but the mechanism for this strain rate dependency is not known. Here we investigate the nano scale mechanical property changes of human ligament using mechanical testing combined with synchrotron X-ray diffraction. With increasing strain rate, we observe a significant increase in fibril modulus and a reduction of fibril to tissue strain ratio, revealing that tissue-level stiffening is mainly due to the stiffening of collagen fibrils. Further, we show that the reduction in fibril deformation at higher strain rates is due to reduced molecular strain and fibrillar gaps, and is associated with rapid disruption of matrix-fibril bonding. This reduction in number of interfibrillar cross-links explains the changes in fibril strain; this is verified through computational modelling.
Synergistic effect of mutagenesis and truncation to improve a polyesterase from Clostridium botulinum for polyester hydrolysis
Authors: Biundo Antonino , Reich Johanna , Ribitsch Doris , Guebitz Georg M.
Published: February 2018

The activity of the esterase (Cbotu_EstA) from Clostridium botulinum on the polyester poly(ethylene terephthalate) (PET) was improved by concomitant engineering of two different domains. On the one hand, the zinc-binding domain present in Cbotu_EstA was subjected to site-directed mutagenesis. On the other hand, a specific domain consisting of 71 amino acids at the N-terminus of the enzyme was deleted. Interestingly, a combination of substitution of residues present in the zinc-binding domain (e.g. S199A) synergistically increased the activity of the enzyme on PET seven fold when combined to the truncation of 71 amino acids at the N-terminus of the enzyme only. Overall, when compared to the native enzyme, the combination of truncation and substitutions in the zinc-binding domain lead to a 50-fold activity improvement. Moreover, analysis of the kinetic parameters of the Cbotu_EstA variants indicated a clear shift of activity from water soluble (i.e. para-nitrophenyl butyrate) to insoluble polymeric substrates. These results evidently show that the interaction with non-natural polymeric substrates provides targets for enzyme engineering.