bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic Efficiency in Digital Pathology
Authors: Mills Anne M. , Gradecki Sarah E. , Horton Bethany J. , Blackwell Rebecca , Moskaluk Christopher A. , Mandell James W. , Mills Stacey E. , Cathro Helen P.
Published: September 2017

Prior work has shown that digital images and microscopic slides can be interpreted with comparable diagnostic accuracy. Although accuracy has been well-validated, the interpretative time for digital images has scarcely been studied and concerns about efficiency remain a major barrier to adoption. We investigated the efficiency of digital pathology when compared with glass slide interpretation in the diagnosis of surgical pathology biopsy and resection specimens. Slides were pulled from 510 surgical pathology cases from 5 organ systems (gastrointestinal, gynecologic, liver, bladder, and brain). Original diagnoses were independently confirmed by 2 validating pathologists. Diagnostic slides were scanned using the Philips IntelliSite Pathology Solution. Each case was assessed independently on digital and optical by 3 reading pathologists, with a ≥6 week washout period between modalities. Reading pathologists recorded assessment times for each modality; digital times included time to load the case. Diagnostic accuracy was determined based on whether a rendered diagnosis differed significantly from the original diagnosis. Statistical analysis was performed to assess for differences in interpretative times across modalities. All 3 reading pathologists showed comparable diagnostic accuracy across optical and digital modalities (mean major discordance rates with original diagnosis: 4.8% vs. 4.4%, respectively). Mean assessment times ranged from 1.2 to 9.1 seconds slower on digital versus optical. The slowest reader showed a significant learning effect during the course of the study so that digital assessment times decreased over time and were comparable with optical times by the end of the series. Organ site and specimen type did not significantly influence differences in interpretative times. In summary, digital image reading times compare favorably relative to glass slides across a variety of organ systems and specimen types. Mean increase in assessment time is 4 seconds/case. This time can be minimized with experience and may be further balanced by the improved ease of electronic chart access allowed by digital slide viewing, as well as quantitative assessments which can be expedited on digital images.
MAML2 Rearrangements in Variant Forms of Mucoepidermoid Carcinoma
Authors: Bishop Justin A. , Cowan Morgan L. , Shum Chung H. , Westra William H.
Published: September 2017

Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy. Recent studies have shown that most MECs harbor gene fusions involving MAML2—an alteration that appears to be specific for MEC, a finding that could be diagnostically useful. While most cases of MEC are histologically straightforward, uncommon variants can cause considerable diagnostic difficulty. We present 2 variants of MEC for which MAML2 studies were crucial in establishing a diagnosis: a previously undescribed ciliated variant, and the recently described Warthin-like variant. All cases of ciliated and Warthin-like MEC were retrieved from the archives of The Johns Hopkins Hospital. Break-apart fluorescence in situ hybridization for MAML2 was performed on all cases. One ciliated MEC and 6 Warthin-like MECs were identified. The ciliated MEC presented as a 4.6 cm cystic lymph node metastasis originating from the tongue base in a 47-year-old woman. The Warthin-like MECs presented as parotid masses ranging in size from 1.2 to 3.3 (mean, 2.7 cm) in 4 women and 2 men. The ciliated MEC consisted of macrocystic spaces punctuated by tubulopapillary proliferations of squamoid cells and ciliated columnar cells. The Warthin-like MECs were comprised of cystic spaces lined by multilayered oncocytic to squamoid cells surrounded by a circumscribed cuff of lymphoid tissue with germinal centers. In these cases, the Warthin-like areas dominated the histologic picture. Conventional MEC, when present, represented a minor tumor component. MAML2 rearrangements were identified in all cases. Warthin-like MEC, and now a ciliated form of MEC, are newly described variants of a common salivary gland carcinoma. Unfamiliarity with these novel forms, unanticipated cellular features (eg, cilia), and morphologic overlap with mundane benign processes (eg, developmental ciliated cysts, Warthin tumor) or other carcinomas (eg, ciliated human papillomavirus–related carcinoma) may render these variants susceptible to misdiagnosis. These unusual variants appear to consistently harbor MAML2 fusions—a finding that establishes a clear link to conventional MEC and provides a valuable adjunct in establishing the diagnosis.
Recurrent BRAF Gene Fusions in a Subset of Pediatric Spindle Cell Sarcomas
Authors: Kao Yu-Chien , Fletcher Christopher D.M. , Alaggio Rita , Wexler Leonard , Zhang Lei , Sung Yun-Shao , Orhan Dicle , Chang Wei-Chin , Swanson David , Dickson Brendan C. , Antonescu Cristina R.
Published: September 2017

Infantile fibrosarcomas (IFS) represent a distinct group of soft tissue tumors occurring in patients under 2 years of age and most commonly involving the extremities. Most IFS show recurrent ETV6-NTRK3 gene fusions, sensitivity to chemotherapy, and an overall favorable clinical outcome. However, outside these well-defined pathologic features, no studies have investigated IFS lacking ETV6-NTRK3 fusions, or tumors with the morphology resembling IFS in older children. This study was triggered by the identification of a novel SEPT7-BRAF fusion in an unclassified retroperitoneal spindle cell sarcoma in a 16-year-old female by targeted RNA sequencing. Fluorescence in situ hybridization screening of 9 additional tumors with similar phenotype and lacking ETV6-NTRK3 identified 4 additional cases with BRAF gene rearrangements in the pelvic cavity (n=2), paraspinal region (n=1), and thigh (n=1) of young children (0 to 3 y old). Histologically, 4 cases including the index case shared a fascicular growth of packed monomorphic spindle cells, with uniform nuclei and fine chromatin, and a dilated branching vasculature; while the remaining case was composed of compact cellular sheets of short spindle to ovoid cells. In addition, a minor small blue round cell component was present in 1 case. Mitotic activity ranged from 1 to 9/10 high power fields. Immunohistochemical stains were nonspecific, with only focal smooth muscle actin staining demonstrated in 3 cases tested. Of the remaining 5 BRAF negative cases, further RNA sequencing identified 1 case with EML4-NTRK3 in an 1-year-old boy with a foot IFS, and a second case with TPM3-NTRK1 fusion in a 7-week-old infant with a retroperitoneal lesion. Our findings of recurrent BRAF gene rearrangements in tumors showing morphologic overlap with IFS expand the genetic spectrum of fusion-positive spindle cell sarcomas, to include unusual presentations, such as older children and adolescents and predilection for axial location, thereby opening new opportunities for kinase-targeted therapeutic intervention.
Diagnostic and Prognostic Biomarkers of Adrenal Cortical Carcinoma
Authors: Mete Ozgur , Gucer Hasan , Kefeli Mehmet , Asa Sylvia L.
Published: September 2017

The diagnosis of low-grade adrenal cortical carcinoma (ACC) confined to the adrenal gland can be challenging. Although there are diagnostic and prognostic molecular tests for ACC, they remain largely unutilized. We examined the diagnostic and prognostic value of altered reticulin framework and the immunoprofile of biomarkers including IGF-2, proteins involved in cell proliferation and mitotic spindle regulation (Ki67, p53, BUB1B, HURP, NEK2), DNA damage repair (PBK, γ-H2AX), telomere regulation (DAX, ATRX), wnt-signaling pathway (beta-catenin) and PI3K signaling pathway (PTEN, phospho-mTOR) in a tissue microarray of 50 adenomas and 43 carcinomas that were characterized for angioinvasion as defined by strict criteria, Weiss score, and mitotic rate–based tumor grade. IGF-2 and proteins involved in cell proliferation and mitotic spindle regulation (Ki67, p53, BUB1B, HURP, NEK2), DNA damage proteins (PBK, γ-H2AX), regulators of telomeres (DAXX, ATRX), and beta-catenin revealed characteristic expression profiles enabling the distinction of carcinomas from adenomas. Not all biomarkers were informative in all carcinomas. IGF-2 was the most useful biomarker of malignancy irrespective of tumor grade and cytomorphologic features, as juxtanuclear Golgi-pattern IGF-2 reactivity optimized for high specificity was identified in up to 80% of carcinomas and in no adenomas. Loss rather than qualitative alterations of the reticulin framework yielded statistical difference between carcinoma and adenoma. Angioinvasion defined as tumor cells invading through a vessel wall and intravascular tumor cells admixed with thrombus proved to be the best prognostic parameter, predicting adverse outcome in the entire cohort as well as within low-grade ACCs. Low mitotic tumor grade, Weiss score, global loss of DAXX expression, and high phospho-mTOR expression correlated with disease-free survival, but Weiss score and biomarkers failed to predict adverse outcome in low-grade disease. Our results underscore the importance of careful morphologic assessment coupled with ancillary diagnostic and prognostic biomarkers of ACC.
Sentinel Lymph Nodes in Classic Invasive Lobular Carcinoma of the Breast
Authors: Patel Ami , D’Alfonso Timothy , Cheng Esther , Hoda Syed A.
Published: September 2017

The assessment of sentinel lymph nodes (SLN) on hematoxylin and eosin (H&E)–stained sections in cases of classic type of invasive lobular carcinoma (cILC) is considered unreliable, particularly in cases with minimal involvement, that is by either isolated tumor cells (pN0i+) or micrometastases (pN1mi). Although the impact of minimal SLN involvement has been shown to be insignificant in most clinical trials (even though cILC was either under-represented or not separated in the respective cohorts), the results of MIRROR trial did emphasize the need for additional therapy in cases with minimally involved SLN to ensure improved disease-free survival. We sought to study the role of cytokeratin immunohistochemistry (CK-IHC) in evaluating SLN in cILC. A total of 582 cILC cases with SLN diagnosed over a 12-year period (2005 to 2016) were reviewed. In all, 394/582 (68%) cases had H&E(−)/CK(−) SLN. In total, 188/582 (32%) cases showed some degree of SLN involvement of which 143/582 (25%) cases had readily identifiable SLN involvement on H&E slides. Overall, 45/582 (7.7%) cases had H&E(−)/CK(+) SLN. The following data relate to the latter subset of 45 cases. Mean age of patients: 61 y (range: 32 to 86 y); right: 24 (53%), left: 21 (47%); multifocal and/or multicentric: 22 (49%); mean size: 2.0 cm (range: 0.25 to 4.4 cm); mean number of SLN: 2.5; mean number of involved SLN: 1.2; and cases with prior needle core or excisional biopsy: 45 (100%). CK(+) cells were identified in isolation or in loose clusters, either in subcapsular sinuses or nodal cortex or both. Overall, 30/45 (67%) showed ≤200 CK(+) cells (ie, pN0i+), and 15/45 (33%) showed >200 CK(+) cells (ie, pN1mi). In total, 15/45 (33%) cases underwent axillary lymph node dissection, of which 4/45 (9%) cases were positive. cILC recurred in 3/45 (7%) cases. On statistical analyses, the number of CK(+) cells (≤/>200) did not correlate with either axillary lymph node-positivity or with recurrence. Number of CK(+) cells (≤/>200) readily distinguished pN0i+ from pN1mi based on AJCC’s numerical criteria. CK(+) cells could be quantified in linear terms (ie, AJCC’s size criteria of pN0i+ and pN1mi was applicable) in only 2 cases. On the basis of these findings, the use of CK-IHC staining should be considered for SLN in cases of cILC to ensure detection, and precise determination of extent, of involvement; however, the prognostic significance of this procedure would have to await results of additional studies with long-term follow-up.
Epidemiology of Admissions From the Emergency Department Among Febrile Infants Younger Than 90 Days in the United States, 2002 to 2012
Authors: Nguyen Diana K. , Fleischman Ross J. , Friedlander Scott , Zangwill Kenneth M.
Published: September 2017

Background and Objectives

Febrile infants younger than 90 days are often subjected to invasive diagnostic evaluation and hospitalization to monitor for serious bacterial infection (SBI) despite recent changes in SBI risk and advances in diagnostics. Nationwide provider practices, over time, are unknown for this group. Our objective was to determine the likelihood of admission and associated complications of care for such infants, particularly those at lowest risk for SBI.

Methods

This is a retrospective cohort study including multisite emergency department (ED) visits using administrative data from the Pediatric Emergency Care Applied Research Network Core Data Project. We examined uncomplicated febrile infants younger than 90 days seen in the ED from 2002 to 2012 who did not have an explicit infectious diagnosis, critical illness, or chronic condition.

Results

We identified 38,224 infants, among whom, 11,600 (31%) were admitted. We observed a 3% increase in ED admission every year during the study period (P < 0.05). Age less than 30 days and black race were independent predictors of admission (P < 0.01). We identified 227 complications of care in the ED. Among those with a specified cause, 49% were attributed to antibiotic use or procedures related to the diagnosis and empiric treatment of suspected infection.

Conclusions

Despite the decreasing risk of SBI and diagnostic advances during the study period, the odds of hospital admission increased for febrile infants at low risk for sepsis. We also provide first data on therapeutic and diagnostic test–related adverse events in this setting. These data provide further justification for a consensus guideline on management of such infants.
Abusive Injuries Are Worse Than Vehicular Injuries
Authors: Robertson Brian D. , Abbe Marisa , Pelletier Jamie , Hennes Halim
Published: September 2017

Objectives

The objective of this study was to compare the injury severity and outcome of motor vehicle and nonaccidental traumatic injuries and examine trends in mortality rates over time.

Methods

We reviewed data from 2005 to 2013 from a level 1 pediatric trauma center including demographics, injury severity, and outcomes. Primary outcomes of interest were mortality rates and hospital length of stay.

Results

Injury severity scores were significantly worse for nonaccidental traumas (NATs) (P < 0.001) compared with motor vehicle collisions and motor pedestrian collisions. Nonaccidental traumas were also found to have significantly longer length of stay and higher fatality rates (P < 0.001). Significant differences were also found for the types of injuries sustained for head, extremity, trunk, and other injuries (P < 0.001), and for internal injuries (P < 0.01. Admission rates also dropped for both motor vehicle collisions and motor pedestrian collisions across the 9-year period (P < 0.001) but remained stable for NATs.

Conclusion

In this study population, more severe injuries, higher mortality rates, and longer hospital stays were observed in pediatric NAT compared with those sustained through vehicular means. Furthermore, we observed statistically significant declines in motor vehicle–related injuries compared with NAT.
The Effect of External Thermomechanical Stimulation and Distraction on Reducing Pain Experienced by Children During Blood Drawing
Authors: Inal Sevil , Kelleci Meral
Published: September 2017

This study aimed to investigate the sole and combined effects of external thermomechanical stimulation and distraction in pain relief of children during blood drawing.

This is a randomized clinical trial. The sample consisted of 218 children aged 6 to 12 years who were randomly assigned to 4 groups: group 1 received no intervention, group 2 received external thermomechanical stimulation using Buzzy, group 3 received distraction via DistrACTION Cards, and group 4 received a combination of both external thermomechanical stimulation and distraction. Preprocedural anxiety was assessed through observers' observations using the Children's Anxiety and Pain Scale. Children's pain levels were assessed by themselves, observers, and parents, as reported using the Faces Pain Scale–Revised. Preprocedural anxiety did not differ significantly (P > 0.05). When the 3 study groups were compared with the control group, all 3 groups had significantly lower pain levels than the control group (P < 0.001). The lowest pain level was measured in the combined condition (Buzzy and DistrACTION Cards). The mean score of the device group was lower than the distraction group.
New perspectives in ocean acidification research: editor's introduction to the special feature on ocean acidification
Authors: Munday Philip L.
Published: September 2017

Ocean acidification, caused by the uptake of additional carbon dioxide (CO
2
) from the atmosphere, will have far-reaching impacts on marine ecosystems (Gattuso & Hansson 2011
Ocean acidification
. Oxford University Press). The predicted changes in ocean chemistry will affect whole biological communities and will occur within the context of global warming and other anthropogenic stressors; yet much of the biological research conducted to date has tested the short-term responses of single species to ocean acidification conditions alone. While an important starting point, these studies may have limited predictive power because they do not account for possible interactive effects of multiple climate change drivers or for ecological interactions with other species. Furthermore, few studies have considered variation in responses among populations or the evolutionary potential within populations. Therefore, our knowledge about the potential for marine organisms to adapt to ocean acidification is extremely limited. In 2015, two of the pioneers in the field, Ulf Riebesell and Jean-Pierre Gattuso, noted that to move forward as a field of study, future research needed to address critical knowledge gaps in three major areas: (i) multiple environmental drivers, (ii) ecological interactions and (iii) acclimation and adaptation (Riebesell and Gattuso 2015
Nat. Clim. Change
5
, 12–14 (
doi:10.1038/nclimate2456
)). In May 2016, more than 350 researchers, students and stakeholders met at the 4th International Symposium on the Ocean in a High-CO
2
World in Hobart, Tasmania, to discuss the latest advances in understanding ocean acidification and its biological consequences. Many of the papers presented at the symposium reflected this shift in focus from short-term, single species and single stressor experiments towards multi-stressor and multispecies experiments that address knowledge gaps about the ecological impacts of ocean acidification on marine communities. The nine papers in this Special Feature are from authors who attended the symposium and address cutting-edge questions and emerging topics in ocean acidification research, across the taxonomic spectrum from plankton to top predators. They cover the three streams of research identified as crucial to understanding the biological impacts of ocean acidification: (i) the relationship with other environmental drivers, (ii) the effects on ecological process and species interactions, and (iii) the role that individual variation, phenotypic plasticity and adaptation will have in shaping the impacts of ocean acidification and warming on marine ecosystems.
The requirement of Mettl3-promoted
MyoD
mRNA maintenance in proliferative myoblasts for skeletal muscle differentiation
Authors: Kudou Kensuke , Komatsu Tetsuro , Nogami Jumpei , Maehara Kazumitsu , Harada Akihito , Saeki Hiroshi , Oki Eiji , Maehara Yoshihiko , Ohkawa Yasuyuki
Published: September 2017

Myogenic progenitor/stem cells retain their skeletal muscle differentiation potential by maintaining myogenic transcription factors such as MyoD. However, the mechanism of how MyoD expression is maintained in proliferative progenitor cells has not been elucidated. Here, we found that
MyoD
expression was reduced at the mRNA level by cell cycle arrest in S and G2 phases, which in turn led to the absence of skeletal muscle differentiation. The reduction of
MyoD
mRNA was correlated with the reduced expression of factors regulating RNA metabolism, including methyltransferase like 3 (Mettl3), which induces N
6
-methyladenosine (m
6
A) modifications of RNA. Knockdown of Mettl3 revealed that
MyoD
RNA was specifically downregulated and that this was caused by a decrease in processed, but not unprocessed, mRNA. Potential m
6
A modification sites were profiled by m
6
A sequencing and identified within the 5′ untranslated region (UTR) of
MyoD
mRNA. Deletion of the 5′ UTR revealed that it has a role in
MyoD
mRNA processing. These data showed that Mettl3 is required for
MyoD
mRNA expression in proliferative myoblasts.
Discovery of novel representatives of bilaterian neuropeptide families and reconstruction of neuropeptide precursor evolution in ophiuroid echinoderms
Authors: Zandawala Meet , Moghul Ismail , Yañez Guerra Luis Alfonso , Delroisse Jérôme , Abylkassimova Nikara , Hugall Andrew F. , O'Hara Timothy D. , Elphick Maurice R.
Published: September 2017

Neuropeptides are a diverse class of intercellular signalling molecules that mediate neuronal regulation of many physiological and behavioural processes. Recent advances in genome/transcriptome sequencing are enabling identification of neuropeptide precursor proteins in species from a growing variety of animal taxa, providing new insights into the evolution of neuropeptide signalling. Here, detailed analysis of transcriptome sequence data from three brittle star species,
Ophionotus victoriae
,
Amphiura filiformis
and
Ophiopsila aranea
, has enabled the first comprehensive identification of neuropeptide precursors in the class Ophiuroidea of the phylum Echinodermata. Representatives of over 30 bilaterian neuropeptide precursor families were identified, some of which occur as paralogues. Furthermore, homologues of endothelin/CCHamide, eclosion hormone, neuropeptide-F/Y and nucleobinin/nesfatin were discovered here in a deuterostome/echinoderm for the first time. The majority of ophiuroid neuropeptide precursors contain a single copy of a neuropeptide, but several precursors comprise multiple copies of identical or non-identical, but structurally related, neuropeptides. Here, we performed an unprecedented investigation of the evolution of neuropeptide copy number over a period of approximately 270 Myr by analysing sequence data from over 50 ophiuroid species, with reference to a robust phylogeny. Our analysis indicates that the composition of neuropeptide ‘cocktails’ is functionally important, but with plasticity over long evolutionary time scales.
Glareosin: a novel sexually dimorphic urinary lipocalin in the bank vole,
Myodes glareolus
Authors: Loxley Grace M. , Unsworth Jennifer , Turton Michael J. , Jebb Alexandra , Lilley Kathryn S. , Simpson Deborah M. , Rigden Daniel J. , Hurst Jane L. , Beynon Robert J.
Published: September 2017

The urine of bank voles (
Myodes glareolus
) contains substantial quantities of a small protein that is expressed at much higher levels in males than females, and at higher levels in males in the breeding season. This protein was purified and completely sequenced at the protein level by mass spectrometry. Leucine/isoleucine ambiguity was completely resolved by metabolic labelling, monitoring the incorporation of dietary deuterated leucine into specific sites in the protein. The predicted mass of the sequenced protein was exactly consonant with the mass of the protein measured in bank vole urine samples, correcting for the formation of two disulfide bonds. The sequence of the protein revealed that it was a lipocalin related to aphrodisin and other odorant-binding proteins (OBPs), but differed from all OBPs previously described. The pattern of secretion in urine used for scent marking by male bank voles, and the similarity to other lipocalins used as chemical signals in rodents, suggest that this protein plays a role in male sexual and/or competitive communication. We propose the name glareosin for this novel protein to reflect the origin of the protein and to emphasize the distinction from known OBPs.
Detecting rare asymmetrically methylated cytosines and decoding methylation patterns in the honeybee genome
Authors: Welsh Laura , Maleszka Ryszard , Foret Sylvain
Published: September 2017

Context-dependent gene expression in eukaryotes is controlled by several mechanisms including cytosine methylation that primarily occurs in the CG dinucleotides (CpGs). However, less frequent non-CpG asymmetric methylation has been found in various cell types, such as mammalian neurons, and recent results suggest that these sites can repress transcription independently of CpG contexts. In addition, an emerging view is that CpG hemimethylation may arise not only from deregulation of cellular processes but also be a standard feature of the methylome. Here, we have applied a novel approach to examine whether asymmetric CpG methylation is present in a sparsely methylated genome of the honeybee, a social insect with a high level of epigenetically driven phenotypic plasticity. By combining strand-specific ultra-deep amplicon sequencing of illustrator genes with whole-genome methylomics and bioinformatics, we show that rare asymmetrically methylated CpGs can be unambiguously detected in the honeybee genome. Additionally, we confirm differential methylation between two phenotypically and reproductively distinct castes, queens and workers, and offer new insight into the heterogeneity of brain methylation patterns. In particular, we challenge the assumption that symmetrical methylation levels reflect symmetry in the underlying methylation patterns and conclude that hemimethylation may occur more frequently than indicated by methylation levels. Finally, we question the validity of a prior study in which most of cytosine methylation in this species was reported to be asymmetric.
Perception of global image contrast involves transparent spatial filtering and the integration and suppression of local contrasts (not RMS contrast)
Authors: Meese Tim S. , Baker Daniel H. , Summers Robert J.
Published: September 2017

When adjusting the contrast setting on a television set, we experience a perceptual change in the global image contrast. But how is that statistic computed? We addressed this using a contrast-matching task for checkerboard configurations of micro-patterns in which the contrasts and spatial spreads of two interdigitated components were controlled independently. When the patterns differed greatly in contrast, the higher contrast determined the perceived global contrast. Crucially, however, low contrast additions of one pattern to intermediate contrasts of the other caused a paradoxical
reduction
in the perceived global contrast. None of the following metrics/models predicted this: max, linear sum, average, energy, root mean squared (RMS), Legge and Foley. However, a nonlinear gain control model, derived from contrast detection and discrimination experiments, incorporating wide-field summation and suppression, did predict the results with no free parameters, but only when spatial filtering was removed. We conclude that our model describes fundamental processes in human contrast vision (the pattern of results was the same for expert and naive observers), but that above threshold—when contrast pedestals are clearly visible—vision's spatial filtering characteristics become transparent, tending towards those of a delta function prior to spatial summation. The global contrast statistic from our model is as easily derived as the RMS contrast of an image, and since it more closely relates to human perception, we suggest it be used as an image contrast metric in practical applications.
Pragmatic analysis of the electric submerged arc furnace continuum
Authors: Karalis K. , Karkalos N. , Antipas G. S. E. , Xenidis A.
Published: September 2017

A transient mathematical model was developed for the description of fluid flow, heat transfer and electromagnetic phenomena involved in the production of ferronickel in electric arc furnaces. The key operating variables considered were the thermal and electrical conductivity of the slag and the shape, immersion depth and applied electric potential of the electrodes. It was established that the principal stimuli of the velocities in the slag bath were the electric potential and immersion depth of the electrodes and the thermal and electrical conductivities of the slag. Additionally, it was determined that, under the set of operating conditions examined, the maximum slag temperature ranged between 1756 and 1825 K, which is in accordance with industrial measurements. Moreover, it was affirmed that contributions to slag stirring due to Lorentz forces and momentum forces due to the release of carbon monoxide bubbles from the electrode surface were negligible.
Influence of solvents in the preparation of cobalt sulfide for supercapacitors
Authors: Anil Kumar Yedluri , Srinivasa Rao S. , Punnoose Dinah , Venkata Tulasivarma Chebrolu , Gopi Chandu V. V. M. , Prabakar Kandasamy , Kim Hee-Je
Published: September 2017

In this study, cobalt sulfide (CoS) electrodes are synthesized using various solvents such as water, ethanol and a combination of the two via a facile chemical bath deposition method on Ni foam. The crystalline nature, chemical states and surface morphology of the prepared CoS nanoparticles are characterized using X-ray diffraction, X-ray photoelectron spectroscopy, scanning electron microscopy and transition electron microscopy. The electrochemical properties of CoS electrodes are also evaluated using cyclic voltammetry, galvanostatic charge–discharge and electrochemical impedance spectroscopy. When used as an electrode for a supercapacitor, CoS prepared with ethanol as a solvent exhibits a capacitance of 41.36 F g
−1
at 1.5 A g
−1
, which is significantly better than that prepared using water and water/ethanol-based solvents (31.66 and 18.94 F g
−1
at 1.5 A g
−1
, respectively). This superior capacitance is attributed to the ideal surface morphology of the solvent, which allows for easy diffusion of electrolyte ions into the inner region of the electrode. High electrical conduction enables a high rate capability. These results suggest that CoS nanoparticles are highly promising for energy storage applications as well as photocatalysis, electrocatalysis, water splitting and solar cells, among others. These results show that CoS is a promising positive electrode material for practical supercapacitors.
Design of cinnamaldehyde amino acid Schiff base compounds based on the quantitative structure–activity relationship
Authors: Wang Hui , Jiang Mingyue , Li Shujun , Hse Chung-Yun , Jin Chunde , Sun Fangli , Li Zhuo
Published: September 2017

Cinnamaldehyde amino acid Schiff base (CAAS) is a new class of safe, bioactive compounds which could be developed as potential antifungal agents for fungal infections. To design new cinnamaldehyde amino acid Schiff base compounds with high bioactivity, the quantitative structure–activity relationships (QSARs) for CAAS compounds against
Aspergillus niger
(
A. niger
) and
Penicillium citrinum (P. citrinum)
were analysed. The QSAR models (
R
2
 = 0.9346 for
A. niger
,
R
2
 = 0.9590 for
P. citrinum,
) were constructed and validated. The models indicated that the molecular polarity and the Max atomic orbital electronic population had a significant effect on antifungal activity. Based on the best QSAR models, two new compounds were designed and synthesized. Antifungal activity tests proved that both of them have great bioactivity against the selected fungi.
Highly efficient synthesis of [60]fullerene oxides by plasma jet
Authors: Jiang Sheng-Peng , Duan Shengxia , Liu Kai-Qing , Yang Xiao-Yu , Cheng Cheng , Li Jiaxing , Wang Guan-Wu
Published: September 2017

Atmospheric pressure nonequilibrium plasma jet has been applied to the synthesis of [60]fullerene oxides (C
60
O
n
) for the first time. C
60
O and C
60
O
2
were produced and isolated in high yields up to 44% and 21%, respectively. The structural assignment of C
60
O was confirmed by comparison with the reported spectroscopic data. Theoretical calculations of
13
C NMR chemical shifts for eight isomers of C
60
O
2
were performed and compared with the experimental data to assign the most possible structure for the obtained C
60
O
2
dominantly as an
e
isomer.
Celebrating 30 years of science from the James Clerk Maxwell Telescope
Authors: Robson Ian , Holland Wayne S. , Friberg Per
Published: September 2017

The James Clerk Maxwell Telescope (JCMT) has been the world’s most successful single-dish telescope at submillimetre wavelengths since it began operations in 1987. From the pioneering days of single-element photometers and mixers, through to the state-of-the-art imaging and spectroscopic cameras, the JCMT has been associated with a number of major scientific discoveries. Famous for the discovery of ‘SCUBA’ galaxies, which are responsible for a large fraction of the far-infrared background, the JCMT has pushed the sensitivity limits arguably more than any other facility in this most difficult of wavebands in which to observe. Closer to home, the first images of huge discs of cool debris around nearby stars gave us clues to the evolution of planetary systems, further evidence of the importance of studying astrophysics in the submillimetre region. Now approaching the 30th anniversary of the first observations, the telescope continues to carry out unique and innovative science. In this review article, we look back on some of the major scientific highlights from the past 30 years.
Stability of the shear-thinning boundary-layer flow over a flat inclined plate
Authors: Griffiths P. T.
Published: September 2017

In this study, we consider the boundary-layer flow of an inelastic non-Newtonian fluid over an inclined flat plate. Using two popular generalized Newtonian models, we determine base flow profiles and associated linear stability results for a range shear-thinning fluids. In addition to neutral stability curves, we also present results concerning the linear growth of the Tollmien–Schlichting waves as they propagate downstream. Furthermore, to gain an insight into the underlying physical mechanisms affecting the destabilization of the disturbances, an integral energy equation is derived and energy calculations are presented. Results from all three analyses suggest that the effect of shear-thinning will act to stabilize the boundary-layer flow. Consequently, it can be argued that the addition of shear-thinning agents could act as a passive control mechanism for flows of this nature.
A vertebrate retina with segregated colour and polarization sensitivity
Authors: Novales Flamarique Iñigo
Published: September 2017

Besides colour and intensity, some invertebrates are able to independently detect the polarization of light. Among vertebrates, such separation of visual modalities has only been hypothesized for some species of anchovies whose cone photoreceptors have unusual ultrastructure that varies with retinal location. Here, I tested this hypothesis by performing physiological experiments of colour and polarization discrimination using the northern anchovy,Engraulis mordax. Optic nerve recordings showed that the ventro-temporal (VT), but not the ventro-nasal (VN), retina was polarization sensitive, and this coincided with the exclusive presence of polarization-sensitive photoreceptors in the VT retina. Spectral (colour) sensitivity recordings from the VN retina indicated the contribution of two spectral cone mechanisms to the optic nerve response, whereas only one contributed to the VT retina. This was supported by the presence of only one visual pigment in the VT retina and two in the VN retina, suggesting that only the VN retina was associated with colour sensitivity. Behavioural tests further demonstrated that anchovies could discriminate colour and the polarization of light using the ventral retina. Thus, in analogy with the visual system of some invertebrates, the northern anchovy has a retina with segregated retinal pathways for colour and polarization vision.
Adaptation to a novel family environment involves both apparent and cryptic phenotypic changes
Authors: Schrader Matthew , Jarrett Benjamin J. M. , Rebar Darren , Kilner Rebecca M.
Published: September 2017

Cryptic evolution occurs when evolutionary change is masked by concurrent environmental change. In most cases, evolutionary changes in the phenotype are masked by changing abiotic factors. However, evolutionary change in one trait might also be masked by evolutionary change in another trait, a phenomenon referred to as evolutionary environmental deterioration. Nevertheless, detecting this second type of cryptic evolution is challenging and there are few compelling examples. Here, we describe a likely case of evolutionary environmental deterioration occurring in experimental burying beetle (Nicrophorus vespilloides) populations that are adapting to a novel social environment that lacks post-hatching parental care. We found that populations rapidly adapted to the removal of post-hatching parental care. This adaptation involved clear increases in breeding success and larval density (number of dispersing larvae produced per gram of breeding carcass), which in turn masked a concurrent increase in the mean larval mass across generations. This cryptic increase in larval mass was accomplished through a change in the reaction norm that relates mean larval mass to larval density. Our results suggest that cryptic evolution might be commonplace in animal families, because evolving trophic and social interactions can potentially mask evolutionary change in other traits, like body size.
A Rescorla-Wagner Drift-Diffusion Model of Conditioning and Timing
Authors: Luzardo André , Alonso Eduardo , Mondragón Esther
Published: September 2017

Computational models of classical conditioning have made significant contributions to the theoretic understanding of associative learning, yet they still struggle when the temporal aspects of conditioning are taken into account. Interval timing models have contributed a rich variety of time representations and provided accurate predictions for the timing of responses, but they usually have little to say about associative learning. In this article we present a unified model of conditioning and timing that is based on the influential Rescorla-Wagner conditioning model and the more recently developed Timing Drift-Diffusion model. We test the model by simulating 10 experimental phenomena and show that it can provide an adequate account for 8, and a partial account for the other 2. We argue that the model can account for more phenomena in the chosen set than these other similar in scope models: CSC-TD, MS-TD, Learning to Time and Modular Theory. A comparison and analysis of the mechanisms in these models is provided, with a focus on the types of time representation and associative learning rule used.

Author Summary

How does the time of events affect the way we learn about associations between these events? Computational models have made great contributions to our understanding of associative learning, but they usually do not perform very well when time is taken into account. Models of timing have reached high levels of accuracy in describing timed behaviour, but they usually do not have much to say about associations. A unified approach would involve combining associative learning and timing models into a single framework. This article takes just this approach. It combines the influential Rescorla-Wagner associative model with a timing model based on the Drift-Diffusion process, and shows how the resultant model can account for a number of learning and timing phenomena. The article also compares the new model to others that are similar in scope.
Elucidation of the 14-3-3ζ interactome reveals critical roles of RNA splicing factors during adipogenesis
Authors: Mugabo Yves , Sadeghi Mina , Fang Nancy N. , Mayor Thibault , Lim Gareth E.
Published: September 2017

Adipogenesis is facilitated by a complex signaling network requiring strict temporal and spatial organization of effector molecules. Molecular scaffolds, such as 14-3-3 proteins, coordinate such events, and we have previously identified 14-3-3ζ as an essential scaffold in adipocyte differentiation. The interactome of 14-3-3ζ is large and diverse, and it is possible that novel adipogenic factors may be present within it. Mouse embryonic fibroblasts from mice over-expressing a TAP-epitope-tagged 14-3-3ζ molecule were generated, and following the induction of adipogenesis, TAP-14-3-3ζ complexes were purified, followed by mass spectrometry analysis to determine the 14-3-3ζ interactome. Over 100 proteins were identified as being unique to adipocyte differentiation, of which 56 were novel interacting partners. Previously established regulators of adipogenesis (ie, Ptrf/Cavin1 and Phb2) were found within the 14-3-3ζ interactome, confirming the ability of this approach to identify regulators of adipocyte differentiation. An enrichment of proteins in the interactome related to RNA metabolism, processing, and splicing was identified, and analysis of transcriptomic data revealed that 14-3-3ζ depletion in 3T3-L1 cells affected the alternative splicing of mRNA during adipocyte differentiation. Of the RNA splicing factors within the 14-3-3ζ interactome, depletion of Hnrnpf, Hnrnpk, Ddx6, and Sfpq by siRNA revealed essential roles of these proteins in adipogenesis and their roles in the alternative splicing ofLpin1. In summary, novel adipogenic factors can be detected within the 14-3-3ζ interactome, and further characterization of additional proteins within the 14-3-3ζ interactome has the potential of identifying novel targets to block the expansion of adipose tissue mass that occurs in obesity.
Protective effect of estrogen against intervertebral disc degeneration is attenuated by miR-221 through targeting estrogen receptor
Authors: Bin Sheng , Youchao Yuan , Xiangyang Liu , Yi Zhang , Hongzhe Liu , Xiongjie Shen , Bin Liu , Lei Chang
Published: September 2017

Intervertebral disc degeneration (IDD) is a multifactorial disease that associates apoptosis, senescence and calcification of cartilage cells, inflammatory response and alterations in the extracellular matrix. Previous documents imply that estrogen and miR-221 may be involved in IDD. This study further investigated their regulatory mechanisms underlying IDD. Normal and degenerated cartilaginous endplates (CEP) tissues were isolated surgically from juvenile patients with idiopathic scoliosis and adult patients with IDD, respectively. PCR and western blot assays showed decreased aggrecan, Col2A1, TGF-β and estrogen receptorα (ERα) levels in CEP, but increased MMP-3, adamts-5, IL-1β, TNF-α, IL-6 and miR-221 levels. CEP cells were harvested from degenerated CEP tissues and treated with doses of 17β-E2. 17β-E2 increased expression of aggrecan and Col2A1 levels in endplate chondrocytes and secretion of TGF-β, but decreased IL-6 secretion. Moreover, 17β-E2 inhibited the apoptosis and cell-cycle arrest in G0/G1, improving the cell viability. These data indicated estrogen confers protective effect against IDD. However, we found that ERα was a target of miR-221 via luciferase assay. miR-221 up-regulation via the mimics or ERα knockdown attenuated these protective effects conferred by estrogen, while intervention of miR-221 via the inhibitors promoted the protective effects. This study provided novel evidence that estrogen confers protective effects of CEP against IDD, however, up-regulated miR-221 in degenerated CEP decreased the protective effects via targeting ERα, thus it may be an important cause for IDD.
Shaping Epigenetic Memory via Genomic Bookmarking: Supplementary Information
Authors: Michieletto D. , Chiang M. , Colì D. , Papantonis A. , Orlandini E. , Cook P. R. , Marenduzzo D.
Published: September 2017

Reconciling the stability of epigenetic patterns with the rapid turnover of histone modifications and their adaptability to external stimuli is an outstanding challenge. Here, we propose a new biophysical mechanism that can establish and maintain robust yet plastic epigenetic domains via genomic bookmarking (GBM). We model chromatin as a recolourable polymer whose segments bear non-permanent histone marks (or colours) which can be modified by “writer” proteins. The three-dimensional chromatin organisation is mediated by protein bridges, or “readers”, such as Polycomb Repressive Complexes and Transcription Factors. The coupling between readers and writers drives spreading of biochemical marks and sustains the memory of local chromatin states across replication and mitosis. In contrast, GBM-targeted perturbations destabilise the epigenetic patterns. Strikingly, we demonstrate that GBM alone can explain the full distribution of Polycomb marks in a whole Drosophila chromosome. We finally suggest that our model provides a starting point for an understanding of the biophysics of cellular differentiation and reprogramming.
Glutamine metabolism regulates Th2 cell differentiation via the α-ketoglutalate-dependent demethylation of histone H3K27
Authors: Kuwahara Makoto , Izumoto Maya , Honda Hiroaki , Inoue Kazuki , Imai Yuuki , Suzuki Junpei , Maruyama Saho , Yasukawa Masaki , Yamashita Masakatsu
Published: September 2017

The acquisition of T cell functions seems to be closely linked to the reprogramming of the metabolic pathway. However, the impact of metabolic changes on the differentiation of helper T cell subsets remains unclear. We found that TCR-mediated activation of glutamine metabolism regulates Th2 cell differentiation via the supplementation of α-ketogulutalate (α-KG) and histone H3K27 demethylation. Deprivation of glutamine or pharmacological inhibition of glutamine metabolism blocks the induction of Th2 cell differentiation without affecting Stat6 phosphorylation. The methylation status of H3K27 at the Th2 cytokine gene locus was significantly increased in Th2 cells cultured under glutamine-deprived conditions. The inhibitory effect of glutamine-deprivation was antagonized by α-KG, and the α-KG-dependent induction of Th2 cell differentiation was reduced inutx-andjmjd3-deficientnaïve CD4 T cells. These findings show that the glutamine-a-ketoglutarate axis is crucial to regulating the epigenetic status at the Th2 cytokine gene locus and subsequent Th2 cell differentiation.
Interoperable genome annotation with GBOL, an extendable infrastructure for functional data mining
Authors: van Dam Jesse C.J. , Koehorst Jasper J. , Vik Jon Olav , Schaap Peter J. , Suarez-Diez Maria
Published: September 2017

Background

A standard structured format is used by the public sequence databases to present genome annotations. A prerequisite for a direct functional comparison is consistent annotation of the genetic elements with evidence statements. However, the current format provides limited support for data mining, hampering comparative analyses at large scale.

Results

The provenance of a genome annotation describes the contextual details and derivation history of the process that resulted in the annotation. To enable interoperability of genome annotations, we have developed the Genome Biology Ontology Language (GBOL) and associated infrastructure (GBOL stack). GBOL is provenance aware and thus provides a consistent representation of functional genome annotations linked to the provenance. GBOL is modular in design, extendible and linked to existing ontologies. The GBOL stack of supporting tools enforces consistency within and between the GBOL definitions in the ontology (OWL) and the Shape Expressions (ShEx) language describing the graph structure. Modules have been developed to serialize the linked data (RDF) and to generate a plain text format files.

Conclusion

The main rationale for applying formalized information models is to improve the exchange of information. GBOL uses and extends current ontologies to provide a formal representation of genomic entities, along with their properties and relations. The deliberate integration of data provenance in the ontology enables review of automatically obtained genome annotations at a large scale. The GBOL stack facilitates consistent usage of the ontology.