Unification of Radio Galaxies and Their Accretion/Jet Properties

We investigate the relation between black hole mass, M_bh, and jet power, Q_jet, for a sample of BL Lacs and radio quasars. We find that BL Lacs are separated from radio quasars by the FR I/II dividing line in M_bh-Q_jet plane, which strongly supports the unification scheme of FR I/BL Lac and FR II/radio quasar. The Eddington ratio distribution of BL Lacs and radio quasars exhibits a bimodal nature with a rough division at L_bol/L_Edd~0.01, which imply that they may have different accretion modes. We calculate the jet power extracted from advection dominated accretion flow (ADAF), and find that it require dimensionless angular momentum of black hole j~0.9-0.99 to reproduce the dividing line between FR I/II or BL Lac/radio quasar if dimensionless accretion rate mdot=0.01 is adopted, which is required by above bimodal distribution of Eddington ratios. Our results suggest that black holes in radio galaxies are rapidly spinning.Comment: To appear JAA in Jun

Patterns of BAP1 protein expression provide insights into prognostic significance and the biology of uveal melanoma

Uveal melanoma (UM) is a rare aggressive intraocular tumour with a propensity for liver metastases, occurring in ∼50% of patients. The tumour suppressor BAP1 is considered to be key in UM progression. Herein, we present the largest study to date investigating cellular expression patterns of BAP1 protein in 165 UMs, correlating these patterns to prognosis. Full clinical, histological, genetic, and follow‐up data were available for all patients. BAP1 gene sequencing was performed on a subset of 26 cases. An independent cohort of 14 UMs was examined for comparison. Loss of nuclear BAP1 (nBAP1) protein expression was observed in 54% (88/165) UMs. nBAP1 expression proved to be a significant independent prognostic parameter: it identified two subgroups within monosomy 3 (M3) UM, which are known to have a high risk of metastasis. Strikingly, nBAP1‐positiveM3 UMs were associated with prolonged survival compared to nBAP1‐negative M3 UMs (Log rank, p = 0.014). nBAP1 protein loss did not correlate with a BAP1 mutation in 23% (6/26) of the UMs analysed. Cytoplasmic BAP1 protein (cBAP1) expression was also observed in UM: although appearing ‘predominantly diffuse’ in most nBAP1‐negative UM, a distinct ‘focal perinuclear’ expression pattern – localized immediately adjacent to the cis Golgi – was seen in 31% (18/59). These tumours tended to carry loss‐of‐function BAP1 mutations. Our study demonstrates loss of nBAP1 expression to be the strongest prognostic marker in UM, confirming its importance in UM progression. Our data suggest that non‐genetic mechanisms account for nBAP1 loss in a small number of UMs. In addition, we describe a subset of nBAP1‐negative UM, in which BAP1 is sequestered in perinuclear bodies, most likely within Golgi, warranting further mechanistic investigation

Artificial Neural Network Inference (ANNI): A Study on Gene-Gene Interaction for Biomarkers in Childhood Sarcomas

Objective: To model the potential interaction between previously identified biomarkers in children sarcomas using artificial neural network inference (ANNI). Method: To concisely demonstrate the biological interactions between correlated genes in an interaction network map, only 2 types of sarcomas in the children small round blue cell tumors (SRBCTs) dataset are discussed in this paper. A backpropagation neural network was used to model the potential interaction between genes. The prediction weights and signal directions were used to model the strengths of the interaction signals and the direction of the interaction link between genes. The ANN model was validated using Monte Carlo cross-validation to minimize the risk of over-fitting and to optimize generalization ability of the model. Results: Strong connection links on certain genes (TNNT1 and FNDC5 in rhabdomyosarcoma (RMS); FCGRT and OLFM1 in Ewing’s sarcoma (EWS)) suggested their potency as central hubs in the interconnection of genes with different functionalities. The results showed that the RMS patients in this dataset are likely to be congenital and at low risk of cardiomyopathy development. The EWS patients are likely to be complicated by EWS-FLI fusion and deficiency in various signaling pathways, including Wnt, Fas/Rho and intracellular oxygen. Conclusions: The ANN network inference approach and the examination of identified genes in the published literature within the context of the disease highlights the substantial influence of certain genes in sarcomas

Developing and Advancing a Cyberinfrastructure to Gain Insights into Research Investments: An Organizing Research Framework

Developing and Advancing a Cyberinfrastructure to Gain Insights into Research Investments: An Organizing Research Framework Although the National Science Foundation (NSF) funds approximately 24% of basic research conducted in America’s colleges and universities (NSF), there is little we know about how NSF-­‐funding decisions have resulted in the current research landscape. This gap was the impetus for a project –Deep Insights Anytime, Anywhere (DIA2)— that begins to address this problem by focusing on NSF investments in undergraduate STEM education research, and how education innovations make an impact and diffuse throughout the STEM education community. The project team has designed an information portal (http://www.dia2.org) to allow researchers and scientists to browse and search public data from NSF to understand what research has taken place in specific areas and to find collaborators. There are many challenges in developing and using such a cyberinfrastructure, but also many potential advantages for practitioners and researchers. In this paper we will specifically discuss the research opportunities provided by DIA2 and present the research framework guiding the DIA2 project—a description of the three major themes/areas of research for the study. It summarizes the research questions and research activities corresponding to each of the themes, presents next steps, and based on our findings, highlights the value of DIA2 to members of the STEM education community. These concentrated efforts can help us better understand the domain of STEM research. Reference NSF. About the National Science Foundation. Retrieved October 14, 2014, from http://nsf.gov/about

Transcriptomic Analyses of Sexual Dimorphism of the Zebrafish Liver and the Effect of Sex Hormones

10.1371/journal.pone.0053562PLoS ONE81

Development and Airworthiness Certification of the Ti6Al4V Inlet Casing Inner Forging

The inlet casing inner has manufactured using Ti-6Al-4V alloy through a closed die-forging route. It undergoes cyclic loads in addition to operating in extreme conditions in high-temperature environments. The demanding mission requirement of these engines necessitates the inlet casing inner to be flawless throughout its life cycle while retaining its structural integrity. It makes the qualification for airworthiness of the casing, a daunting task. In addition, the qualification tests also help to evaluate the design and manufacturing processes (closed die forging) of the inlet casing inner. The tests also provide data for further improvement of the inlet casing inner in terms of strength and fatigue life. It helps to ensure that the inlet casing inner will be able to perform as expected throughout its operational life. All the batch and consolidated test results comply with the relevant ASTM, MIL standards, and test schedule requirements

Influence of sex, age, pubertal maturation and body mass index on circulating white blood cell counts in healthy European adolescents—the HELENA study

Percentiles 10th, 25th, 50th, 75th and 90th are presented for circulating white blood cells (WBC), neutrophils, lymphocytes, monocytes, eosinophils and basophils in healthy European adolescents (12.5–17.5 years, n = 405, 48.9 % boys), considering age, sex, puberty and body mass index (BMI). CD3+ (mature T cells), CD4+ (T helper), CD8+ (T cytotoxic), CD16+56+ (natural killer), CD19+ (B cells), CD3+CD45RA+, CD4+CD45RA+, CD8+CD45RA+ (naïve), CD3+CD45RO+, CD4+CD45RO+ and CD8+CD45RO+ (memory) lymphocytes were also analysed by immunophenotyping. Girls presented higher WBC, neutrophil, CD3+CD45RO+ and CD4+CD45RO+ cell counts and CD3+/CD19+ ratio, and lower CD3+CD45RA+ and CD4+CD45RA+ counts than boys. Age was associated with higher neutrophil counts and CD3+/CD19+, and lower CD19+ counts; in boys, with lower CD3+CD45RA+, CD4+CD45RA+ and CD8+CD45RA+ counts as well; in girls, with higher WBC, CD3+CD45RO+ and CD4+CD45RO+ counts. Pubertal maturation in boys was associated with lower WBC and lymphocyte counts; in girls, with higher basophil, CD3+CD45RO+ and CD4+CD45RO+ values. BMI was associated with higher WBC counts; in boys, also with higher lymphocyte counts; in girls, with higher neutrophil, CD4+, CD3+CD45RO+ and CD4+CD45RO+ counts. Conclusion: Our study provides normative values for circulating immune cells in adolescents, highlighting the importance of considering sex, age, pubertal maturation and BMI when establishing reference ranges for WBC in paediatric populations

Cerebrospinal fluid neopterin as marker of the meningo-encephalitic stage of Trypanosoma brucei gambiense sleeping sickness.

BACKGROUND: Sleeping sickness, or human African trypanosomiasis (HAT), is a protozoan disease that affects rural communities in sub-Saharan Africa. Determination of the disease stage, essential for correct treatment, represents a key issue in the management of patients. In the present study we evaluated the potential of CXCL10, CXCL13, ICAM-1, VCAM-1, MMP-9, B2MG, neopterin and IgM to complement current methods for staging Trypanosoma brucei gambiense patients. METHODS AND FINDINGS: Five hundred and twelve T. b. gambiense HAT patients originated from Angola, Chad and the Democratic Republic of the Congo (D.R.C.). Their classification as stage 2 (S2) was based on the number of white blood cells (WBC) (>5/µL) or presence of parasites in the cerebrospinal fluid (CSF). The CSF concentration of the eight markers was first measured on a training cohort encompassing 100 patients (44 S1 and 56 S2). IgM and neopterin were the best in discriminating between the two stages of disease with 86.4% and 84.1% specificity respectively, at 100% sensitivity. When a validation cohort (412 patients) was tested, neopterin (14.3 nmol/L) correctly classified 88% of S1 and S2 patients, confirming its high staging power. On this second cohort, neopterin also predicted both the presence of parasites, and of neurological signs, with the same ability as IgM and WBC, the current reference for staging. CONCLUSIONS: This study has demonstrated that neopterin is an excellent biomarker for staging T. b. gambiense HAT patients. A rapid diagnostic test for detecting this metabolite in CSF could help in more accurate stage determination

Mutations at the Subunit Interface of Yeast Proliferating Cell Nuclear Antigen Reveal a Versatile Regulatory Domain

Acknowledgments We thank Szilvia Minorits for technical assistance. I.U. conceived and designed the project and wrote the manuscript. All authors participated in designing and performing the experiments, and analyzing the results. The authors declare no competing financial interests. This work was also supported by a grant from the National Research, Development and Innovation Office GINOP-2.3.2-15-2016-00001. Funding: This work was supported by Hungarian Science Foundation Grant OTKA 109521 and National Research Development and Innovation Office GINOP-2.3.2-15-2016-00001. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Scaled testing for COVID-19 needs community involvement.

With limited vaccine coverage and in the absence of specific therapeutics, the options to curb the COVID-19 pandemic today are mostly infection prevention measures and diagnostic tests to identify infected individuals rapidly, followed by isolation and contact tracing. The past months have seen significant worldwide scale-up of testing through quantitative PCR (qPCR) detecting nucleic acid of SARS-CoV-2. However, with the current resurgence of cases in Europe and elsewhere, qPCR demand far exceeds capacity. Moreover, qPCR is expensive, requires sophisticated laboratories, well-trained staff, and extensive logistics. Capacity deficits are aggravated in LMICs (Lower and Middle-Income Countries) with rampant shortages of tests kits, qualified staff, and laboratories, compromising clinical utility. Africa CDC reports 23 countries with proxy PCR coverage of <5000 tests/million population [1]. Alternative novel molecular diagnostics such as LAMP, DNAnudge and LAMPore remain widely unscalable. Moreover, even qPCR has its limitations in detecting non-infectious traces of viral RNA [2] and false negativity issues [3]. We conclude that molecular testing for COVID-19 is unfit for reaching scale at the community level