235 research outputs found
Note on Information Entropy for Quantized Normal Distribution
Control Systems Laboratory changed its name to Coordinated Science LaboratoryContract DA-11-022-ORD-72
Notes on the Estimation of Information Measures
Control Systems Laboratory changed its name to Coordinated Science LaboratoryContract DA-36-039-SC-5669
Cutting the Gordian knot : early and complete amino acid sequence confirmation of class II lasso peptides by HCD fragmentation
SAJ would like to thank the University of Aberdeen for an Elphinstone Scholarship. CC-A thanks CONICYT PFCHA/DOCTORADO BECAS CHILE/2016 (#21160585) fellowship and CONICYT Basal Centre Grant for the Centre for Biotechnology and Bioengineering, CeBiB (FB0001). JFC also thanks CONICYT for a National PhD Scholarship (#21110356) and a Visiting Student Scholarship.Peer reviewedPostprin
Unravelling the size distribution of social groups with information theory on complex networks
The minimization of Fisher's information (MFI) approach of Frieden et al.
[Phys. Rev. E {\bf 60} 48 (1999)] is applied to the study of size distributions
in social groups on the basis of a recently established analogy between scale
invariant systems and classical gases [arXiv:0908.0504]. Going beyond the ideal
gas scenario is seen to be tantamount to simulating the interactions taking
place in a network's competitive cluster growth process. We find a scaling rule
that allows to classify the final cluster-size distributions using only one
parameter that we call the competitiveness. Empirical city-size distributions
and electoral results can be thus reproduced and classified according to this
competitiveness, which also allows to correctly predict well-established
assessments such as the "six-degrees of separation", which is shown here to be
a direct consequence of the maximum number of stable social relationships that
one person can maintain, known as Dunbar's number. Finally, we show that scaled
city-size distributions of large countries follow the same universal
distribution
Dissipation time and decay of correlations
We consider the effect of noise on the dynamics generated by
volume-preserving maps on a d-dimensional torus. The quantity we use to measure
the irreversibility of the dynamics is the dissipation time. We focus on the
asymptotic behaviour of this time in the limit of small noise. We derive
universal lower and upper bounds for the dissipation time in terms of various
properties of the map and its associated propagators: spectral properties,
local expansivity, and global mixing properties. We show that the dissipation
is slow for a general class of non-weakly-mixing maps; on the opposite, it is
fast for a large class of exponentially mixing systems which include uniformly
expanding maps and Anosov diffeomorphisms.Comment: 26 Pages, LaTex. Submitted to Nonlinearit
Runaway Events Dominate the Heavy Tail of Citation Distributions
Statistical distributions with heavy tails are ubiquitous in natural and
social phenomena. Since the entries in heavy tail have disproportional
significance, the knowledge of its exact shape is very important. Citations of
scientific papers form one of the best-known heavy tail distributions. Even in
this case there is a considerable debate whether citation distribution follows
the log-normal or power-law fit. The goal of our study is to solve this debate
by measuring citation distribution for a very large and homogeneous data. We
measured citation distribution for 418,438 Physics papers published in
1980-1989 and cited by 2008. While the log-normal fit deviates too strong from
the data, the discrete power-law function with the exponent does
better and fits 99.955% of the data. However, the extreme tail of the
distribution deviates upward even from the power-law fit and exhibits a
dramatic "runaway" behavior. The onset of the runaway regime is revealed
macroscopically as the paper garners 1000-1500 citations, however the
microscopic measurements of autocorrelation in citation rates are able to
predict this behavior in advance.Comment: 6 pages, 5 Figure
MultiMetEval: comparative and multi-objective analysis of genome-scale metabolic models
Comparative metabolic modelling is emerging as a novel field, supported by the development of reliable and standardized approaches for constructing genome-scale metabolic models in high throughput. New software solutions are needed to allow efficient comparative analysis of multiple models in the context of multiple cellular objectives. Here, we present the user-friendly software framework Multi-Metabolic Evaluator (MultiMetEval), built upon SurreyFBA, which allows the user to compose collections of metabolic models that together can be subjected to flux balance analysis. Additionally, MultiMetEval implements functionalities for multi-objective analysis by calculating the Pareto front between two cellular objectives. Using a previously generated dataset of 38 actinobacterial genome-scale metabolic models, we show how these approaches can lead to exciting novel insights. Firstly, after incorporating several pathways for the biosynthesis of natural products into each of these models, comparative flux balance analysis predicted that species like Streptomyces that harbour the highest diversity of secondary metabolite biosynthetic gene clusters in their genomes do not necessarily have the metabolic network topology most suitable for compound overproduction. Secondly, multi-objective analysis of biomass production and natural product biosynthesis in these actinobacteria shows that the well-studied occurrence of discrete metabolic switches during the change of cellular objectives is inherent to their metabolic network architecture. Comparative and multi-objective modelling can lead to insights that could not be obtained by normal flux balance analyses. MultiMetEval provides a powerful platform that makes these analyses straightforward for biologists. Sources and binaries of MultiMetEval are freely available from https://github.com/PiotrZakrzewski/MetEval/downloads
Age Does Matter in Adolescents and Young Adults versus Older Adults with Advanced Melanoma; A National Cohort Study Comparing Tumor Characteristics, Treatment Pattern, Toxicity and Response
Cutaneous melanoma is a common type of cancer in Adolescents and Young Adults (AYAs, 15-39 years of age). However, AYAs are underrepresented in clinical trials investigating new therapies and the outcomes from these therapies for AYAs are therefore unclear. Using prospectively collected nation-wide data from the Dutch Melanoma Treatment Registry (DMTR), we compared baseline characteristics, mutational profiles, treatment strategies, grade 3-4 adverse events (AEs), responses and outcomes in AYAs (n = 210) and older adults (n = 3775) who were diagnosed with advanced melanoma between July 2013 and July 2018. Compared to older adults, AYAs were more frequently female (51% versus 40%, p = 0.001), and had a better Eastern Cooperative Oncology Group performance status (ECOG 0 in 54% versus 45%, p = 0.004). BRAF and NRAS mutations were age dependent, with more BRAF V600 mutations in AYAs (68% versus 46%) and more NRAS mutations in older adults (13% versus 21%), p < 0.001. This finding translated in distinct first-line treatment patterns, where AYAs received more initial targeted therapy. Overall, grade 3-4 AE percentages following first-line systemic treatment were similar for AYAs and older adults; anti-PD-1 (7% versus 14%, p = 0.25), anti-CTLA-4 (16% versus 33%, p = 0.12), anti-PD-1 + anti-CTLA-4 (67% versus 56%, p = 0.34) and BRAF/MEK-inhibition (14% versus 23%, p = 0.06). Following anti-CTLA-4 treatment, no AYAs experienced a grade 3-4 colitis, while 17% of the older adults did (p = 0.046). There was no difference in response to treatment between AYAs and older adults. The longer overall survival observed in AYAs (hazard ratio (HR) 0.7; 95% CI 0.6-0.8) was explained by the increased cumulative incidence of non-melanoma related deaths in older adults (sub-distribution HR 2.8; 95% CI 1.5-4.9), calculated by competing risk analysis. The results of our national cohort study show that baseline characteristics and mutational profiles differ between AYAs and older adults with advanced melanoma, leading to different treatment choices made in daily practice. Once treatment is initiated, AYAs and older adults show similar tumor responses and melanoma-specific survival
Safety and Efficacy of Checkpoint Inhibition in Patients With Melanoma and Preexisting Autoimmune Disease:A Cohort Study
BACKGROUND: Because immune checkpoint inhibition (ICI) can cause immune-related adverse events (irAEs) mimicking immunologic diseases, patients with preexisting autoimmune disease (AID) have been excluded from clinical trials. OBJECTIVE: To evaluate the safety and efficacy of ICI in patients with advanced melanoma with and without AID. DESIGN: Nationwide cohort study. SETTING: The Netherlands. PATIENTS: 4367 patients with advanced melanoma enrolled in the Dutch Melanoma Treatment Registry (DMTR) between July 2013 and July 2018 and followed through February 2019. MEASUREMENTS: Patient, clinical, and treatment characteristics; irAEs of grade 3 or higher; treatment response; and survival. RESULTS: A total of 415 patients (9.5%) had AID, categorized as rheumatologic AID (n = 227), endocrine AID (n = 143), inflammatory bowel disease (IBD) (n = 55), or "other" (n = 8). Of these, 228 patients (55%) were treated with ICI (vs. 2546 [58%] without AID); 87 were treated with anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4), 187 with anti-programmed cell death 1 (PD-1), and 34 with the combination. The incidences of irAEs of grade 3 or higher in patients with AID were 30% (95% CI, 21% to 41%) with anti-CTLA-4, 17% (CI, 12% to 23%) with anti-PD-1, and 44% (CI, 27% to 62%) with combination therapy; for patients without AID, the incidences were 30% (CI, 27% to 33%) (n = 916), 13% (CI, 12% to 15%) (n = 1540), and 48% (CI, 43% to 53%) (n = 388), respectively. Patients with AID more often discontinued anti-PD-1 treatment because of toxicity than patients without AID (17% [CI, 12% to 23%] vs. 9% [CI, 8% to 11%]). Patients with IBD were more prone to anti-PD-1-induced colitis (6 / 31 = 19% [CI, 7% to 37%]) than patients with other AIDs (3% [CI, 0% to 6%]) and patients without AID (2% [CI, 2% to 3%]). The objective response rate was similar in patients with versus without AID who were treated with anti-CTLA-4 (10% [CI, 5% to 19%] vs. 16% [CI, 14% to 19%]), anti-PD-1 (40% [CI, 33% to 47%] vs. 44% [CI, 41% to 46%]), or the combination (39% [CI, 20% to 59%] vs. 43% [CI, 38% to 49%]). Survival did not differ between patients with and those without AID (median, 13 months [CI, 10 to 16 months] vs. 14 months [CI, 13 to 15 months]). LIMITATION: Information was limited on AID severity and immunosuppressive treatment. CONCLUSION: Response to ICI with anti-CTLA-4, anti-PD-1, or their combination for advanced melanoma and overall incidence of any irAEs of grade 3 or higher were similar in patients with and without preexisting AID. However, severe colitis and toxicity requiring early discontinuation of treatment occurred more frequently among patients with preexisting IBD, warranting close follow-up. PRIMARY FUNDING SOURCE: The Netherlands Organization for Health Research and Development
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