bluuebunny/crossref_metadata_2025_split huggingface dataset:
Benchmarking cryo-EM single particle analysis workflow
Authors: Kim Laura Y. , Rice William J. , Eng Edward T. , Kopylov Mykhailo , Cheng Anchi , Raczkowski Ashleigh M. , Jordan Kelsey D. , Bobe Daija , Potter Clinton S. , Carragher Bridget 
Published: May 2018

AbstractCryo electron microscopy facilities running multiple instruments and serving users with varying skill levels need a robust and reliable method for benchmarking both the hardware and software components of their single particle analysis workflow. The workflow is complex, with many bottlenecks existing at the specimen preparation, data collection and image analysis steps; the samples and grid preparation can be of unpredictable quality, there are many different protocols for microscope and camera settings, and there is a myriad of software programs for analysis that can depend on dozens of settings chosen by the user. For this reason, we believe it is important to benchmark the entire workflow, using a standard sample and standard operating procedures, on a regular basis. This provides confidence that all aspects of the pipeline are capable of producing maps to high resolution. Here we describe benchmarking procedures using a test sample, rabbit muscle aldolase.
3D Shape Modeling for Cell Nuclear Morphological Analysis and Classification
Authors: Kalinin Alexandr A. , Allyn-Feuer Ari , Ade Alex , Fon Gordon-Victor , Meixner Walter , Dilworth David , Husain Syed S. , de Wet Jeffrey R. , Higgins Gerald A. , Zheng Gen , Creekmore Amy , Wiley John W. , Verdone James E. , Veltri Robert W. , Pienta Kenneth J. , Coffey Donald S. , Athey Brian D. , Dinov Ivo D. 
Published: May 2018

AbstractQuantitative analysis of morphological changes in a cell nucleus is important for the understanding of nuclear architecture and its relationship with pathological conditions such as cancer. However, dimensionality of imaging data, together with a great variability of nuclear shapes, presents challenges for 3D morphological analysis. Thus, there is a compelling need for robust 3D nuclear morphometric techniques to carry out population-wide analysis. We propose a new approach that combines modeling, analysis, and interpretation of morphometric characteristics of cell nuclei and nucleoli in 3D. We used robust surface reconstruction that allows accurate approximation of 3D object boundary. Then, we computed geometric morphological measures characterizing the form of cell nuclei and nucleoli. Using these features, we compared over 450 nuclei with about 1,000 nucleoli of epithelial and mesenchymal prostate cancer cells, as well as 1,000 nuclei with over 2,000 nucleoli from serum-starved and proliferating fibroblast cells. Classification of sets of 9 and 15 cells achieved accuracy of 95.4% and 98%, respectively, for prostate cancer cells, and 95% and 98% for fibroblast cells. To our knowledge, this is the first attempt to combine these methods for 3D nuclear shape modeling and morphometry into a highly parallel pipeline workflow for morphometric analysis of thousands of nuclei and nucleoli in 3D.
A conserved glycine harboring disease-associated mutations is required for slow deactivation and high Ca2+ permeability in NMDA receptors
Authors: Amin Johansen B. , Leng Xiaoling , Gochman Aaron , Zhou Huan-Xiang , Wollmuth Lonnie P. 
Published: May 2018

ABSTRACTA variety of de novo and inherited missense mutations associated with neurological disorders are found in the NMDA receptor M4 transmembrane helices, which are peripheral to the pore domain in eukaryotic ionotropic glutamate receptors. Subsets of these mutations affect receptor gating with dramatic effects, including in one instance halting it, occurring at a conserved glycine near the extracellular end of M4. Functional experiments and molecular dynamic simulations of constructs with and without substitutions at this glycine indicate that it acts as a hinge, permitting the intracellular portion of the ion channel to laterally expand. This expansion stabilizes long-lived open states leading to slow deactivation and high Ca2+ permeability. Our studies provide a functional and structural framework for the effect of missense mutations on NMDARs at central synapses and highlight how the M4 segment may represent a pathway for intracellular modulation of NMDA receptor function.
Self-organization of Plk4 regulates symmetry breaking in centriole duplication
Authors: Yamamoto Shohei , Kitagawa Daiju 
Published: May 2018

AbstractDuring centriole duplication, a single daughter centriole is formed near the mother centriole. The mechanism that determines a single duplication site is unknown. Here, we demonstrate that intrinsic self-organization of Plk4 underlies symmetry breaking in centriole duplication. We show that in its nonphosphorylated state, Plk4 preferentially self-assembles via a disordered linker and that this self-assembly is prevented by autophosphorylation. Consistently, the dissociation dynamics of centriolar Plk4 are controlled by autophosphorylation. We further found that autophophorylated Plk4 is localized as a single focus around the mother centriole before procentriole formation, and is subsequently targeted for STIL-HsSAS6 loading. Perturbing Plk4 self-organization affects the asymmetry of centriolar Plk4 distribution and centriole duplication. We propose that the spatial patterning of Plk4 directs a single duplication site per mother centriole.
Water motion as a transformation mechanism of algal communities structure in Lake Baikal
Authors: Kravtsova Lyubov S. , Mizandrontse Igor B. , Vorobyova Svetlana S. , Izhboldina Lyudmila A. , Mincheva Elena V. , Potyomkina Tatyana G. , Triboy Tatyana I. , Khanaev Igor V. , Sherbakovv Dmitry Yu. , Fedotov Andrey P. 
Published: May 2018

AbstractThe diversity of algal communities of phytoplankton and meio-and macrophytes was investigated in Lake Baikal. Fragments ofSpirogyrathallomes were recorded in the phytoplankton community of Southern Baikal, which had never been recorded before in its composition. It was also established that the structure of benthic algal communities changed in comparison with that in 2000 due to intense development of filamentous algae, particularlySpirogyra. Its lowest biomass was recorded in the surf zone and wave breaking, whereas the highest biomass was registered in the area of weakened effect of waves on the bottom. The cover percent of the bottom with filamentous algae in different areas of the coastal zone varied from 0 to 100%. Hydraulic characteristics ofSpirogyrawere the same as those of planktonic diatoms. The circulation currents and wave effect on the bottom favoured transfer and distribution ofSpirogyrafrom the location of its intense development into the coastal area of Lake Baikal.
Genomic analysis of EuropeanDrosophila melanogasterpopulations reveals longitudinal structure, continent-wide selection, and previously unknown DNA viruses
Authors: Kapun Martin , Barrón Maite G. , Staubach Fabian , Obbard Darren J. , Wiberg R. Axel W. , Vieira Jorge , Goubert Clément , Rota-Stabelli Omar , Kankare Maaria , Bogaerts-Márquez María , Haudry Annabelle , Waidele Lena , Kozeretska Iryna , Pasyukova Elena G. , Loeschcke Volker , Pascual Marta , Vieira Cristina P. , Serga Svitlana , Montchamp-Moreau Catherine , Abbott Jessica , Gibert Patricia , Porcelli Damiano , Posnien Nico , Sánchez-Gracia Alejandro , Grath Sonja , Sucena Élio , Bergland Alan O. , Guerreiro Maria Pilar Garcia , Onder Banu Sebnem , Argyridou Eliza , Guio Lain , Schou Mads Fristrup , Deplancke Bart , Vieira Cristina , Ritchie Michael G. , Zwaan Bas J. , Tauber Eran , Orengo Dorcas J. , Puerma Eva , Aguadé Montserrat , Schmidt Paul S. , Parsch John , Betancourt Andrea J. , Flatt Thomas , González Josefa 
Published: May 2018

AbstractGenetic variation is the fuel of evolution, with standing genetic variation especially important for short-term evolution and local adaptation. To date, studies of spatio-temporal patterns of genetic variation in natural populations have been challenging, as comprehensive sampling is logistically difficult, and sequencing of entire populations costly. Here, we address these issues using a collaborative approach, sequencing 48 pooled population samples from 32 locations, and perform the first continent-wide genomic analysis of genetic variation in EuropeanDrosophila melanogaster. Our analyses uncover longitudinal population structure, provide evidence for continent-wide selective sweeps, identify candidate genes for local climate adaptation, and document clines in chromosomal inversion and transposable element frequencies. We also characterise variation among populations in the composition of the fly microbiome, and identify five new DNA viruses in our samples.
Response to “No evidence of functional co-adaptation between clustered microRNAs”
Authors: Wang Yirong , Zhang Hong , Lu Jian 
Published: May 2018

AbstractmicroRNAs (miRNAs) are a class of endogenously expressed small non-coding RNAs that regulate target genes at the post-transcriptional level. One significant feature of miRNA is that their genomic locations are often clustered together in the genome. In a previous study (Wang, et al. 2016), we proposed a “functional co-adaptation” model to explain how clustering helps new miRNAs survive and develop functions during long-term evolution. In a manuscript recently posted at bioRxiv (doi:10.1101/274811), Marco claimed that he re-analyzed our data and came to a different conclusion. However, we found his analyses were conducted in an inappropriate approach. He also claimed that the absence of substitution in highly conserved miRNAs does not support the “functional co-adaption” model based on the misunderstanding of our model. In summary, the analyses and claims of Marco, which are flawed, do not refute our model.
DUSP28 is a novel biomarker responsible for aggravating malignancy via the autocrine signaling pathways in metastatic pancreatic cancer
Authors: Lee Jungwhoi , Lee Jungsul , Choi Chulhee , Kim Jae Hoon 
Published: May 2018

AbstractPancreatic cancer remains one of the most dangerous cancers with a grave prognosis. We previously reported that pancreatic cancer cells can secrete dual specificity phosphatise 28 (DUSP28) to the cultured medium. However, its biological function is poorly understood. Here, we have identified the function of DUSP28 in human metastatic pancreatic cancer. Treatment with recombinant DUSP28 (rDUSP28) significantly increased the migration, invasion, and viability of metastatic pancreatic cancer cells through the activation of CREB, AKT, and ERK1/2 signaling pathways. Furthermore, rDUSP28 acted as an oncogenic reagent through the interaction with integrin α1 in metastatic pancreatic cancer cells. In addition, rDUSP28 induced pro-angiogenic effects in human umbilical vein endothelial cells (HUVECs). Administration of rDUSP28 also produced tumor growth in vivo. Notably, sDUSP28 can easily be detected by immunoassay. The results establish the rationale for sDUSP28 as a promising therapeutic target and biomarker for metastatic pancreatic cancer patients.
Automated cellular structure extraction in biological images with applications to calcium imaging data
Authors: Mishne Gal , Coifman Ronald R. , Lavzin Maria , Schiller Jackie 
Published: May 2018

AbstractRecent advances in experimental methods in neuroscience enable measuring in-vivo activity of large populations of neurons at cellular level resolution. To leverage the full potential of these complex datasets and analyze the dynamics of individual neurons, it is essential to extract high-resolution regions of interest, while addressing demixing of overlapping spatial components and denoising of the temporal signal of each neuron. In this paper, we propose a data-driven solution to these challenges, by representing the spatiotemporal volume as a graph in the image plane. Based on the spectral embedding of this graph calculated across trials, we propose a new clustering method, Local Selective Spectral Clustering, capable of handling overlapping clusters and disregarding clutter. We also present a new nonlinear mapping which recovers the structural map of the neurons and dendrites, and global video denoising. We demonstrate our approach on in-vivo calcium imaging of neurons and apical dendrites, automatically extracting complex structures in the image domain, and denoising and demixing their time-traces.
Criticality in Tumor Evolution and Clinical Outcome
Authors: Persi Erez , Wolf Yuri I. , Leiserson Mark D.M. , Koonin Eugene V. , Ruppin Eytan 
Published: May 2018

AbstractHow mutation and selection determine the fitness landscape of tumors and hence clinical outcome is an open fundamental question in cancer biology, crucial for the assessment of therapeutic strategies and resistance to treatment. Here we explore the mutation-selection phase-diagram of 6721 primary tumors representing 23 cancer types, by quantifying the overall somatic point mutation load (ML) and selection (dN/dS) in the entire proteome of each tumor. We show thatMLstrongly correlates with patient survival, revealing two opposing regimes around a critical point. In lowMLcancers, high number of mutations indicates poor prognosis, whereas highMLcancers show the opposite trend, due to mutational meltdown. Although the majority of cancers evolve near neutrality, deviations are observed at extremeMLs. Cancers with the highestMLevolve under purifying selection, whereas those with the lowestMLshow signatures of positive selection, demonstrating how selection affects cancer fitness. Moreover, different cancers occupy specific positions on theML-dN/dSplane, revealing a diversity of evolutionary trajectories. These results support and expand the theory of tumor evolution and its non-linear effects on survival.Significance StatementIt remains an open fundamental question how mutation and selection co-determine the course of cancer evolution. We construct a selection-mutation phase diagram, using tumor mutation load and selection strength as key variables, and assess their association with clinical outcome. We demonstrate the existence of a biphasic evolutionary regime, whereby beyond a criticalML, the fitness of tumors decreases with the number of mutations, while the proteome evolves near neutrality. Deviations from neutrality in extremeMLelucidate how positive and purifying selections maintain tumor fitness. These results empirically corroborate the existence of a critical state in cancer evolution predicted by theory, and have fundamental and likely clinical implications.
A mechanism-based computational model to capture the interconnections among epithelial-mesenchymal transition, cancer stem cells and Notch-Jagged signaling
Authors: Bocci Federico , Jolly Mohit K. , George Jason , Levine Herbert , Onuchic José N. 
Published: May 2018

AbstractEpithelial-mesenchymal transition (EMT) and cancer stem cell formation (CSCs) are two fundamental and well-studied processes contributing to cancer metastasis and tumor relapse. Cells can undergo a partial EMT to attain a hybrid epithelial/mesenchymal (E/M) phenotype or a complete EMT to attain a mesenchymal one. Similarly, cells can reversibly gain or lose ‘stemness’. This plasticity in cell states is modulated by signaling pathways such as Notch. However, the interconnections among the cell states enabled by EMT, CSCs and Notch signaling remain elusive. Here, we devise a computational model to investigate the coupling among the core decision-making circuits for EMT, CSCs and the Notch pathway. Our model predicts that hybrid E/M cells are most likely to associate with stemness traits and exhibit enhanced Notch-Jagged signaling – a pathway that is implicated in therapeutic resistance. Further, we show that the position of the ‘stemness window’ on the ‘EMT axis’ is varied by altering the coupling strength between EMT and CSC circuits, and/or modulating Notch signaling. Finally, we analyze the gene expression profile of CSCs from several cancer types and observe a heterogeneous distribution along the ‘EMT axis’, suggesting that different subsets of CSCs may exist with varying phenotypes along the epithelial-mesenchymal plasticity axis. Our computational model offers insights into the complex EMT-stemness interplay and provides a platform to investigate the effects of therapeutic perturbations such as treatment with metformin, a common anti-diabetic drug that has been associated with decreased cancer incidence and increased lifespan of patients. Our mechanism-based model helps explain how metformin can both inhibit EMT and blunt the aggressive potential of CSCs simultaneously, by driving the cells out of a hybrid E/M stem-like state with enhanced Notch-Jagged signaling.
Strategic planning and performance of SMEs in Ghana
Authors: Donkor Jacob , Donkor George Nana Agyekum , Kwarteng Collins Kankam 
Published: May 2018

Purpose
This paper aims to examine the interacting effect of market dynamism and strategic planning on the performance of small- and medium-scale enterprises (SMEs) in Ghana.

Design/methodology/approach
This study has used quantitative approach in dealing with the interacting effect of market dynamic on strategic planning and SMEs’ performance in Ghana. Purposive sampling is used to select 200 small- and medium-sized manufacturing and service firms in Ghana. The hierarchical multiple regression analysis is performed to test the hypotheses.

Findings
This study finds that a consistent application of strategic planning methodologies contributes to the advancement of SME performance in Ghana. In addition, it was ascertained that market dynamism has a significant positive relationship with firm performance, although its effect is not significant. Finally, the study reveals that market dynamism only influences SME performance when there is strategic planning.

Research limitations/implications
The findings are limited to the SMEs in Ghana. The study of market dynamism, strategic planning and performance is a very complex activity; therefore, to gather rich data on such research work may be best accomplished if the researchers adopt mixed method data gathering techniques. This will enrich the understanding on market dynamism, strategic planning and SMEs’ performance relationship.

Practical implications
The findings of this research work offer guidance to owners or managers considering how to develop market dynamics and strategic planning to enhance firm performance.

Originality/value
This study reports on an obvious gap in the prevailing literature that few empirical research works have explored on the possible impacts of market dynamism and strategic planning on performance of SMEs in a third world country.
Status and conditions of small- and medium-sized enterprises as predictors in empowering rural communities in Samar Island, Philippines
Authors: Miranda Asterio Tenedero , Miranda Juneth Lourdes Fiel 
Published: May 2018

Purpose
This study aims to determine the status and conditions of small and medium enterprises (SMEs) as predictors in empowering the rural communities of Samar Island, Philippines. Specifically, it aimed to describe SMEs’ organizational variables, and assess their conditions in terms of membership/ownership structure; leadership; policies, systems and procedures; resource mobilization; linkages and networking; communication systems; and awards and recognition; determine the level of empowerment of rural communities with SMEs along the aspects of material, perceptual and relational changes; and find out whether significant relationship exist between the organizational variables and the level of empowerment.

Design/methodology/approach
The study is a descriptive survey that utilized structured survey questionnaires, personal interviews and dialogues with the respondents in the actual data collection. The survey involved 18 SMEs from the rural communities of the 12 municipalities from the 3 provinces of Samar Island, as study samples – 6 coming from each province with 2 SMEs in every sub-sector of trading, manufacturing and services. Out of 270 respondents, 256 (94.81 per cent) responded. All statistics were computed using the SPSS computer software.

Findings
The organizational variables of the SMEs such as membership and ownership structure, leadership, policies, systems and procedures, resource mobilization, linkages and networking, communication systems and awards and recognition were assessed to be all “good” and were found to have significant relationship with the level of empowerment of rural communities with SMEs.

Originality/value
The rural communities with SMEs were empowered along the aspects of material, perceptual and relational changes. The result of the study indicated that through SMEs, rural people experienced changes in their lives. The test about the relationship of the organizational variables such as nature and ownership of business enterprise, leadership, policies, systems and procedures, resource mobilization, linkages and networking, communication systems and awards and recognition and the level of empowerment of rural communities as determined by changes in the material, perceptual and relational aspects of rural life proved to have significant relationships.
Lean-green manufacturing: the enabling role of information technology resource
Authors: Ghobakhloo Morteza , Azar Adel , Fathi Masood 
Published: May 2018

PurposeThe purpose of this paper is to contribute to the existing knowledge about the relationships between information technology (IT), lean manufacturing (LM), organizational environmental issues and business performance.Design/methodology/approachA questionnaire-based survey was conducted to collect data from 122 elite manufacturers, and the hypothesized relationships were tested using partial least squares structural equation modeling.FindingsIT competence in LM acts as a lower-order organizational capability, and its business value should be recognized through the intermediate roles of LM effectiveness and environmental management capability. Findings recommend that the net benefits of LM are mainly materialized through waste and pollution reduction and simplified implementation of proactive environmental practices.Research limitations/implicationsAmong other limitations, relying on a rather small sample size and cross-sectional data of this research, and lack of generalizability of findings, tends to have certain limitations. An interesting direction for future research would be to extend this research by assessing interaction of other types of IT resources with LM and organizational environmental issues.Practical implicationsBoth LM and proactive environmental management are information-intensive. Investment in both technological and human aspects of IT resource aimed at increasing the effectiveness of LM activities and proactive environmental practices is imperative for contemporary manufacturers.Originality/valueThis study introduces the IT capability of IT competence in LM and two organizational capabilities of LM effectiveness and environmental management capability. By doing so, the study highlights the significant role of organizational environmental issues in devising firms’ IT and advanced manufacturing technology investment strategies in LM context.