Assessing Research Collaboration through Co-authorship Network Analysis

This is the final version. Available from Society of Research Administrators International via the link in this recordMaterial used with permission from Society of Research Administrators InternationalInterdisciplinary research collaboration is needed to perform transformative science and accelerate innovation. The Science of Team Science strives to investigate, evaluate, and foster team science, including institutional policies that may promote or hinder collaborative interdisciplinary research and the resources and infrastructure needed to promote team science within and across institutions. Social network analysis (SNA) has emerged as a useful method to measure interdisciplinary science through the evaluation of several types of collaboration networks, including co-authorship networks. Likewise, research administrators are responsible for conducting rigorous evaluation of policies and initiatives. Within this paper, we present a case study using SNA to evaluate interprogrammatic collaboration (evidenced by co-authoring scientific papers) from 2007-2014 among scientists who are members of four formal research programs at an NCI-designated Cancer Center, the Markey Cancer Center (MCC) at the University of Kentucky. We evaluate change in network descriptives over time and implement separable temporal exponential-family random graph models (STERGMs) to estimate the effect of author and network variables on the tendency to form a co-authorship tie. We measure the diversity of the articles published over time (Blau's Index) to understand whether the changes in the co-authorship network are reflected in the diversity of articles published by research members. Over the 8-year period, we found increased inter-programmatic collaboration among research members as evidenced by co-authorship of published scientific papers. Over time, MCC Members collaborated more with others outside of their research program and outside their initial dense co-authorship groups, however tie formation continues to be driven by co-authoring with individuals of the same research program and academic department. Papers increased in diversity over time on all measures with the exception of author gender. This inter-programmatic research was fostered by policy changes in cancer center administration encouraging interdisciplinary research through both informal (e.g., annual retreats, seminar series) and formal (e.g., requiring investigators from more than two research programs on applications for pilot funding) means. Within this cancer center, interdisciplinary co-authorship increased over time as policies encouraging this collaboration were implemented. Yet, there is room for improvement in creating more interdisciplinary and diverse ties between research program members.This research was supported by the Research Communications Office as well as the Biostatistics and Bioinformatics and the Cancer Research Informatics Shared Resources of the University of Kentucky Markey Cancer Center, funded by the National Cancer Institute Cancer Center Support Grant (P30CA177558). Dr. Eddens’ contribution was supported in part by a Building Interdisciplinary Research Careers in Women’s Health grant (#K12 DA035150) from the Office of Women’s Health Research, administered by the Department of Obstetrics and Gynecology of the College of Medicine, University of Kentucky. Dr. Vanderford is supported by the University of Kentucky’s Cancer Center Support Grant (NCI P30CA177558) and the Center for Cancer and Metabolism (NIGMS P20GM121327)

On the physical nature of the so-called prominence tornadoes

Funding: Open access publishing supported by the National Technical Library in Prague. S. Gunár and P. Heinzel acknowledge the support from grant 22-34841S of the Czech Science Foundation (GAČR). S. Gunár, P. Heinzel, and M. Zapiór acknowledge the support from the project RVO:67985815 of the Astronomical Institute of the Czech Academy of Sciences. N. Labrosse acknowledges support from STFC grant ST/T000422/1. M. Luna acknowledges support through the Ramón y Cajal fellowship RYC2018-026129-I from the Spanish Ministry of Science and Innovation, the Spanish National Research Agency (Agencia Estatal de Investigación), the European Social Fund through Operational Program FSE 2014 of Employment, Education and Training and the Universitat de les Illes Balears. This publication is part of the R + D + i project PID2020-112791GB-I00, financed by MCIN/AEI/10.13039/501100011033. T. Kucera acknowledges support of the NASA Heliophysics ISFM program. D.H.M. would like to thank the STFC for support via consolidated grant ST/W001195/1.The term ‘tornado’ has been used in recent years to describe several solar phenomena, from large-scale eruptive prominences to small-scale photospheric vortices. It has also been applied to the generally stable quiescent prominences, sparking a renewed interest in what historically was called ‘prominence tornadoes’. This paper carries out an in-depth review of the physical nature of ‘prominence tornadoes’, where their name subconsciously makes us think of violent rotational dynamics. However, after careful consideration and analysis of the published observational data and theoretical models, we conclude that ‘prominence tornadoes’ do not differ in any substantial way from other stable solar prominences. There is simply no unequivocal observational evidence of sustained and coherent rotational movements in quiescent prominences that would justify a distinct category of prominences sharing the name with the well-known atmospheric phenomenon. The visual impression of the column-like silhouettes, the perceived helical motions, or the suggestive Doppler-shift patterns all have a simpler, more likely explanation. They are a consequence of projection effects combined with the presence of oscillations and/or counter-streaming flows. ‘Prominence tornadoes’ are thus just manifestations of the complex nature of solar prominences when observed in specific projections. These coincidental viewing angles, together with the presence of fine-structure dynamics and simple yet profoundly distorting projection effects, may sometimes play havoc with our intuitive understanding of perceived shapes and motions, leading to the incorrect analogy with atmospheric tornadoes.Publisher PDFPeer reviewe

Long-term treatment of uterine fibroids with ulipristal acetate

Objective: To investigate the efficacy and safety of ulipristal acetate (UPA) for long-term treatment of symptomatic uterine fibroids.<p></p> Design: Repeated intermittent open-label UPA courses, each followed by randomized double-blind norethisterone acetate (NETA) or placebo.<p></p> Setting: European clinical gynecology centers.<p></p> Patient(s): Two hundred and nine women with symptomatic fibroids including heavy menstrual bleeding.<p></p> Intervention(s): Patients received up to four 3-month courses of UPA 10 mg daily, immediately followed by 10-day double-blind treatment with NETA (10 mg daily) or placebo.<p></p> Main Outcome Measure(s): Amenorrhea, fibroid volume, endometrial histology.<p></p> Result(s): After the first UPA course, amenorrhea occurred in 79% of women, with median onset (from treatment start) of 4 days (interquartile range, 2–6 days). Median fibroid volume change was −45% (interquartile range, −66%; −25%). Amenorrhea rates were 89%, 88%, and 90% for the 131, 119, and 107 women who received treatment courses 2, 3, and 4, respectively. Median times to amenorrhea were 2, 3, and 3 days for treatment courses 2, 3, and 4, respectively. Median fibroid volume changes from baseline were −63%, −67%, and −72% after treatment courses 2, 3, and 4, respectively. All endometrial biopsies showed benign histology without hyperplasia; NETA did not affect fibroid volume or endometrial histology.<p></p> Conclusion(s): Repeated 3-month UPA courses effectively control bleeding and shrink fibroids in patients with symptomatic fibroids

Informing women about hormone replacement therapy: the consensus conference statement

Background: The risks/benefits balance of hormone replacement therapy is controversial. Information can influence consumers' knowledge and behavior; research findings about hormone replacement therapy are uncertain and the messages provided by the media are of poor quality and incomplete, preventing a fully informed decision making process. We therefore felt that an explicit, rigorous and structured assessment of the information needs on this issue was urgent and we opted for the organisation of a national consensus conference (CC) to assess the current status of the quality of information on hormone replacement therapy (HRT) and re-visit recent research findings on its risks/ benefits. Methods: We chose a structured approach based on the traditional CC method combined with a structured preparatory work supervised by an organising committee (OC) and a scientific board (SB). The OC and SB chose the members of the CC's jury and appointed three multidisciplinary working groups (MWG) which were asked to review clinical issues and different aspects of the quality of information. Before the CC, the three MWGs carried out: A literature review on the risk/benefit profile of HRT and two surveys on the quality of information on lay press and booklets targeted to women. A population survey on women's knowledge, attitude and practice was also carried out. The jury received the documents in advance, listened the presentations during the two-day meeting of the CCs, met immediately after in a closed-door meeting and prepared the final document. Participants were researchers, clinicians, journalists as well as consumers' representatives. Results: Key messages in the CC's deliberation were: a) women need to be fully informed about the transient nature of menopausal symptoms, about HRT risks and benefits and about the availability of non-pharmacological interventions; b) HRT is not recommended to prevent menopausal symptoms; c) the term "HRT" is misleading and "post menopausal hormone therapy" should be the preferred definition. Conclusion: This CC led to the identification of specific information drawbacks. Women are exposed to messages that are often partial, non evidence-based nor transparently developed. The structured and participative methodology of this CC allowed a multidisciplinary perspective and a substantial lay people input

The influence of DNA repair on neurological degeneration, cachexia, skin cancer and internal neoplasms: autopsy report of four xeroderma pigmentosum patients (XP-A, XP-C and XP-D)

BACKGROUND: To investigate the association of DNA nucleotide excision repair (NER) defects with neurological degeneration, cachexia and cancer, we performed autopsies on 4 adult xeroderma pigmentosum (XP) patients with different clinical features and defects in NER complementation groups XP-A, XP-C or XP-D. RESULTS: The XP-A (XP12BE) and XP-D (XP18BE) patients exhibited progressive neurological deterioration with sensorineural hearing loss. The clinical spectrum encompassed severe cachexia in the XP-A (XP12BE) patient, numerous skin cancers in the XP-A and two XP-C (XP24BE and XP1BE) patients and only few skin cancers in the XP-D patient. Two XP-C patients developed internal neoplasms including glioblastoma in XP24BE and uterine adenocarcinoma in XP1BE. At autopsy, the brains of the 44 yr XP-A and the 45 yr XP-D patients were profoundly atrophic and characterized microscopically by diffuse neuronal loss, myelin pallor and gliosis. Unlike the XP-A patient, the XP-D patient had a thickened calvarium, and the brain showed vacuolization of the neuropil in the cerebrum, cerebellum and brainstem, and patchy Purkinje cell loss. Axonal neuropathy and chronic denervation atrophy of the skeletal muscles were observed in the XP-A patient, but not in the XP-D patient. CONCLUSIONS: These clinical manifestations and autopsy findings indicate advanced involvement of the central and peripheral nervous system. Despite similar defects in DNA repair, different clinicopathological phenotypes are seen in the four cases, and therefore distinct patterns of neurodegeneration characterize XP-D, XP-A and XP-C patients

Identification of Apurinic/apyrimidinic endonuclease 1 (APE1) as the endoribonuclease that cleaves c-myc mRNA

Endonucleolytic cleavage of the coding region determinant (CRD) of c-myc mRNA appears to play a critical role in regulating c-myc mRNA turnover. Using 32P-labeled c-myc CRD RNA as substrate, we have purified and identified two endoribonucleases from rat liver polysomes that are capable of cleaving the transcript in vitro. A 17-kDa enzyme was identified as RNase1. Apurinic/apyrimidinic (AP) DNA endonuclease 1 (APE1) was identified as the 35-kDa endoribonuclease that preferentially cleaves in between UA and CA dinucleotides of c-myc CRD RNA. APE1 was further confirmed to be the 35-kDa endoribonuclease because: (i) the endoribonuclease activity of the purified 35-kDa native enzyme was specifically immuno-depleted with APE1 monoclonal antibody, and (ii) recombinant human APE1 generated identical RNA cleavage patterns as the native liver enzyme. Studies using E96A and H309N mutants of APE1 suggest that the endoribonuclease activity for c-myc CRD RNA shares the same active center with the AP-DNA endonuclease activity. Transient knockdown of APE1 in HeLa cells led to increased steady-state level of c-myc mRNA and its half-life. We conclude that the ability to cleave RNA dinucleotides is a previously unidentified function of APE1 and it can regulate c-myc mRNA level possibly via its endoribonuclease activity

Theoretical Analysis of Competing Conformational Transitions in Superhelical DNA

We develop a statistical mechanical model to analyze the competitive behavior of transitions to multiple alternate conformations in a negatively supercoiled DNA molecule of kilobase length and specified base sequence. Since DNA superhelicity topologically couples together the transition behaviors of all base pairs, a unified model is required to analyze all the transitions to which the DNA sequence is susceptible. Here we present a first model of this type. Our numerical approach generalizes the strategy of previously developed algorithms, which studied superhelical transitions to a single alternate conformation. We apply our multi-state model to study the competition between strand separation and B-Z transitions in superhelical DNA. We show this competition to be highly sensitive to temperature and to the imposed level of supercoiling. Comparison of our results with experimental data shows that, when the energetics appropriate to the experimental conditions are used, the competition between these two transitions is accurately captured by our algorithm. We analyze the superhelical competition between B-Z transitions and denaturation around the c-myc oncogene, where both transitions are known to occur when this gene is transcribing. We apply our model to explore the correlation between stress-induced transitions and transcriptional activity in various organisms. In higher eukaryotes we find a strong enhancement of Z-forming regions immediately 5′ to their transcription start sites (TSS), and a depletion of strand separating sites in a broad region around the TSS. The opposite patterns occur around transcript end locations. We also show that susceptibility to each type of transition is different in eukaryotes and prokaryotes. By analyzing a set of untranscribed pseudogenes we show that the Z-susceptibility just downstream of the TSS is not preserved, suggesting it may be under selection pressure

Transcription profiling of lung adenocarcinomas of c-myc-transgenic mice: Identification of the c-myc regulatory gene network

<p>Abstract</p> <p>Background</p> <p>The transcriptional regulator c-Myc is the most frequently deregulated oncogene in human tumors. Targeted overexpression of this gene in mice results in distinct types of lung adenocarcinomas. By using microarray technology, alterations in the expression of genes were captured based on a female transgenic mouse model in which, indeed, c-Myc overexpression in alveolar epithelium results in the development of bronchiolo-alveolar carcinoma (BAC) and papillary adenocarcinoma (PLAC). In this study, we analyzed exclusively the promoters of induced genes by different in silico methods in order to elucidate the c-Myc transcriptional regulatory network.</p> <p>Results</p> <p>We analyzed the promoters of 361 transcriptionally induced genes with respect to c-Myc binding sites and found 110 putative binding sites in 94 promoters. Furthermore, we analyzed the flanking sequences (+/- 100 bp) around the 110 c-Myc binding sites and found Ap2, Zf5, Zic3, and E2f binding sites to be overrepresented in these regions. Then, we analyzed the promoters of 361 induced genes with respect to binding sites of other transcription factors (TFs) which were upregulated by c-Myc overexpression. We identified at least one binding site of at least one of these TFs in 220 promoters, thus elucidating a potential transcription factor network. The analysis correlated well with the significant overexpression of the TFs Atf2, Foxf1a, Smad4, Sox4, Sp3 and Stat5a. Finally, we analyzed promoters of regulated genes which where apparently not regulated by c-Myc or other c-Myc targeted TFs and identified overrepresented Oct1, Mzf1, Ppargamma, Plzf, Ets, and HmgIY binding sites when compared against control promoter background.</p> <p>Conclusion</p> <p>Our in silico data suggest a model of a transcriptional regulatory network in which different TFs act in concert upon c-Myc overexpression. We determined molecular rules for transcriptional regulation to explain, in part, the carcinogenic effect seen in mice overexpressing the c-Myc oncogene.</p