1,109 research outputs found
Weak representations of relation algebras and relational bases
Published versio
A regularisation approach to causality theory for C^{1,1}Lorentzian metrics
We show that many standard results of Lorentzian causality theory remain valid if the regularity of the metric is reduced to C^{1,1}. Our approach is based on regularisations of the metric adapted to the causal structure
How citation boosts promote scientific paradigm shifts and Nobel Prizes
Nobel Prizes are commonly seen to be among the most prestigious achievements
of our times. Based on mining several million citations, we quantitatively
analyze the processes driving paradigm shifts in science. We find that
groundbreaking discoveries of Nobel Prize Laureates and other famous scientists
are not only acknowledged by many citations of their landmark papers.
Surprisingly, they also boost the citation rates of their previous
publications. Given that innovations must outcompete the rich-gets-richer
effect for scientific citations, it turns out that they can make their way only
through citation cascades. A quantitative analysis reveals how and why they
happen. Science appears to behave like a self-organized critical system, in
which citation cascades of all sizes occur, from continuous scientific progress
all the way up to scientific revolutions, which change the way we see our
world. Measuring the "boosting effect" of landmark papers, our analysis reveals
how new ideas and new players can make their way and finally triumph in a world
dominated by established paradigms. The underlying "boost factor" is also
useful to discover scientific breakthroughs and talents much earlier than
through classical citation analysis, which by now has become a widespread
method to measure scientific excellence, influencing scientific careers and the
distribution of research funds. Our findings reveal patterns of collective
social behavior, which are also interesting from an attention economics
perspective. Understanding the origin of scientific authority may therefore
ultimately help to explain, how social influence comes about and why the value
of goods depends so strongly on the attention they attract.Comment: 6 pages, 6 figure
Measuring co-authorship and networking-adjusted scientific impact
Appraisal of the scientific impact of researchers, teams and institutions
with productivity and citation metrics has major repercussions. Funding and
promotion of individuals and survival of teams and institutions depend on
publications and citations. In this competitive environment, the number of
authors per paper is increasing and apparently some co-authors don't satisfy
authorship criteria. Listing of individual contributions is still sporadic and
also open to manipulation. Metrics are needed to measure the networking
intensity for a single scientist or group of scientists accounting for patterns
of co-authorship. Here, I define I1 for a single scientist as the number of
authors who appear in at least I1 papers of the specific scientist. For a group
of scientists or institution, In is defined as the number of authors who appear
in at least In papers that bear the affiliation of the group or institution. I1
depends on the number of papers authored Np. The power exponent R of the
relationship between I1 and Np categorizes scientists as solitary (R>2.5),
nuclear (R=2.25-2.5), networked (R=2-2.25), extensively networked (R=1.75-2) or
collaborators (R<1.75). R may be used to adjust for co-authorship networking
the citation impact of a scientist. In similarly provides a simple measure of
the effective networking size to adjust the citation impact of groups or
institutions. Empirical data are provided for single scientists and
institutions for the proposed metrics. Cautious adoption of adjustments for
co-authorship and networking in scientific appraisals may offer incentives for
more accountable co-authorship behaviour in published articles.Comment: 25 pages, 5 figure
Evolutionary Toggling of Vpx/Vpr Specificity Results in Divergent Recognition of the Restriction Factor SAMHD1
SAMHD1 is a host restriction factor that blocks the ability of lentiviruses such as HIV-1 to undergo reverse transcription in myeloid cells and resting T-cells. This restriction is alleviated by expression of the lentiviral accessory proteins Vpx and Vpr (Vpx/Vpr), which target SAMHD1 for proteasome-mediated degradation. However, the precise determinants within SAMHD1 for recognition by Vpx/Vpr remain unclear. Here we show that evolution of Vpx/Vpr in primate lentiviruses has caused the interface between SAMHD1 and Vpx/Vpr to alter during primate lentiviral evolution. Using multiple HIV-2 and SIV Vpx proteins, we show that Vpx from the HIV-2 and SIVmac lineage, but not Vpx from the SIVmnd2 and SIVrcm lineage, require the C-terminus of SAMHD1 for interaction, ubiquitylation, and degradation. On the other hand, the N-terminus of SAMHD1 governs interactions with Vpx from SIVmnd2 and SIVrcm, but has little effect on Vpx from HIV-2 and SIVmac. Furthermore, we show here that this difference in SAMHD1 recognition is evolutionarily dynamic, with the importance of the N- and C-terminus for interaction of SAMHD1 with Vpx and Vpr toggling during lentiviral evolution. We present a model to explain how the head-to-tail conformation of SAMHD1 proteins favors toggling of the interaction sites by Vpx/Vpr during this virus-host arms race. Such drastic functional divergence within a lentiviral protein highlights a novel plasticity in the evolutionary dynamics of viral antagonists for restriction factors during lentiviral adaptation to its hosts. © 2013 Fregoso et al
The strike rate index: a new index for journal quality based on journal size and the h-index of citations
Quantifying the impact of scientific research is almost always controversial, and there is a need for a uniform method that can be applied across all fields. Increasingly, however, the quantification has been summed up in the impact factor of the journal in which the work is published, which is known to show differences between fields. Here the h-index, a way to summarize an individual's highly cited work, was calculated for journals over a twenty year time span and compared to the size of the journal in four fields, Agriculture, Condensed Matter Physics, Genetics and Heredity and Mathematical Physics. There is a linear log-log relationship between the h-index and the size of the journal: the larger the journal, the more likely it is to have a high h-index. The four fields cannot be separated from each other suggesting that this relationship applies to all fields. A strike rate index (SRI) based on the log relationship of the h-index and the size of the journal shows a similar distribution in the four fields, with similar thresholds for quality, allowing journals across diverse fields to be compared to each other. The SRI explains more than four times the variation in citation counts compared to the impact factor
A Single-Arm, Proof-Of-Concept Trial of Lopimune (Lopinavir/Ritonavir) as a Treatment for HPV-Related Pre-Invasive Cervical Disease
BACKGROUND:
Cervical cancer is the most common female malignancy in the developing nations and the third most common cancer in women globally. An effective, inexpensive and self-applied topical treatment would be an ideal solution for treatment of screen-detected, pre-invasive cervical disease in low resource settings.
METHODS:
Between 01/03/2013 and 01/08/2013, women attending Kenyatta National Hospital's Family Planning and Gynaecology Outpatients clinics were tested for HIV, HPV (Cervista®) and liquid based cervical cytology (LBC -ThinPrep®). HIV negative women diagnosed as high-risk HPV positive with high grade squamous intraepithelial lesions (HSIL) were examined by colposcopy and given a 2 week course of 1 capsule of Lopimune (CIPLA) twice daily, to be self-applied as a vaginal pessary. Colposcopy, HPV testing and LBC were repeated at 4 and 12 weeks post-start of treatment with a final punch biopsy at 3 months for histology. Primary outcome measures were acceptability of treatment with efficacy as a secondary consideration.
RESULTS:
A total of 23 women with HSIL were treated with Lopimune during which time no adverse reactions were reported. A maximum concentration of 10 ng/ml of lopinavir was detected in patient plasma 1 week after starting treatment. HPV was no longer detected in 12/23 (52.2%, 95%CI: 30.6-73.2%). Post-treatment cytology at 12 weeks on women with HSIL, showed 14/22 (63.6%, 95%CI: 40.6-82.8%) had no dysplasia and 4/22 (18.2%, 95%CI: 9.9-65.1%) were now low grade demonstrating a combined positive response in 81.8% of women of which 77.8% was confirmed by histology. These data are supported by colposcopic images, which show regression of cervical lesions.
CONCLUSIONS:
These results demonstrate the potential of Lopimune as a self-applied therapy for HPV infection and related cervical lesions. Since there were no serious adverse events or detectable post-treatment morbidity, this study indicates that further trials are clearly justified to define optimal regimes and the overall benefit of this therapy.
TRIAL REGISTRATION:
ISRCTN Registry 48776874
Search for Exotic Strange Quark Matter in High Energy Nuclear Reactions
We report on a search for metastable positively and negatively charged states
of strange quark matter in Au+Pb reactions at 11.6 A GeV/c in experiment E864.
We have sampled approximately six billion 10% most central Au+Pb interactions
and have observed no strangelet states (baryon number A < 100 droplets of
strange quark matter). We thus set upper limits on the production of these
exotic states at the level of 1-6 x 10^{-8} per central collision. These limits
are the best and most model independent for this colliding system. We discuss
the implications of our results on strangelet production mechanisms, and also
on the stability question of strange quark matter.Comment: 21 pages, 9 figures, to be published in Nuclear Physics A (Carl Dover
memorial edition
The Citation Field of Evolutionary Economics
Evolutionary economics has developed into an academic field of its own,
institutionalized around, amongst others, the Journal of Evolutionary Economics
(JEE). This paper analyzes the way and extent to which evolutionary economics
has become an interdisciplinary journal, as its aim was: a journal that is
indispensable in the exchange of expert knowledge on topics and using
approaches that relate naturally with it. Analyzing citation data for the
relevant academic field for the Journal of Evolutionary Economics, we use
insights from scientometrics and social network analysis to find that, indeed,
the JEE is a central player in this interdisciplinary field aiming mostly at
understanding technological and regional dynamics. It does not, however, link
firmly with the natural sciences (including biology) nor to management
sciences, entrepreneurship, and organization studies. Another journal that
could be perceived to have evolutionary acumen, the Journal of Economic Issues,
does relate to heterodox economics journals and is relatively more involved in
discussing issues of firm and industry organization. The JEE seems most keen to
develop theoretical insights
Maf1, a New Player in the Regulation of Human RNA Polymerase III Transcription
BACKGROUND: Human RNA polymerase III (pol III) transcription is regulated by several factors, including the tumor suppressors P53 and Rb, and the proto-oncogene c-Myc. In yeast, which lacks these proteins, a central regulator of pol III transcription, called Maf1, has been described. Maf1 is required for repression of pol III transcription in response to several signal transduction pathways and is broadly conserved in eukaryotes. METHODOLOGY/PRINCIPAL FINDINGS: We show that human endogenous Maf1 can be co-immunoprecipitated with pol III and associates in vitro with two pol III subunits, the largest subunit RPC1 and the α-like subunit RPAC2. Maf1 represses pol III transcription in vitro and in vivo and is required for maximal pol III repression after exposure to MMS or rapamycin, treatments that both lead to Maf1 dephosphorylation. CONCLUSIONS/SIGNIFICANCE: These data suggest that Maf1 is a major regulator of pol III transcription in human cells
- …