5,428 research outputs found
Maximum entropy models for antibody diversity
Recognition of pathogens relies on families of proteins showing great
diversity. Here we construct maximum entropy models of the sequence repertoire,
building on recent experiments that provide a nearly exhaustive sampling of the
IgM sequences in zebrafish. These models are based solely on pairwise
correlations between residue positions, but correctly capture the higher order
statistical properties of the repertoire. Exploiting the interpretation of
these models as statistical physics problems, we make several predictions for
the collective properties of the sequence ensemble: the distribution of
sequences obeys Zipf's law, the repertoire decomposes into several clusters,
and there is a massive restriction of diversity due to the correlations. These
predictions are completely inconsistent with models in which amino acid
substitutions are made independently at each site, and are in good agreement
with the data. Our results suggest that antibody diversity is not limited by
the sequences encoded in the genome, and may reflect rapid adaptation to
antigenic challenges. This approach should be applicable to the study of the
global properties of other protein families
Second Order Perturbations of Flat Dust FLRW Universes with a Cosmological Constant
We summarize recent results concerning the evolution of second order
perturbations in flat dust irrotational FLRW models with . We
show that asymptotically these perturbations tend to constants in time, in
agreement with the cosmic no-hair conjecture. We solve numerically the second
order scalar perturbation equation, and very briefly discuss its all time
behaviour and some possible implications for the structure formation.Comment: 6 pages, 1 figure. to be published in "Proceedings of the 5th
Alexander Friedmann Seminar on Gravitation and Cosmology", Int. Journ. Mod.
Phys. A (2002). Macros: ws-ijmpa.cls, ws-p9-75x6-50.cl
Averaging in Cosmology
In this paper we discuss the effect of local inhomogeneities on the global
expansion of nearly FLRW universes, in a perturbative setting. We derive a
generic linearized averaging operation for metric perturbations from basic
assumptions, and we explicify the issue of gauge invariance. We derive a gauge
invariant expression for the back-reaction of density inhomogeneities on the
global expansion of perturbed FLRW spacetimes, in terms of observable
quantities, and we calculate the effect quantitatively. Since we do not adopt a
comoving gauge, our result incorporates the back-reaction on the metric due to
scalar velocity and vorticity perturbations. The results are compared with the
results by other authors in this field.Comment: 24 pages, Latex, accepted for publication in Phys. Rev.
Examining if being overweight really confers protection against dementia: Sixty-four year follow-up of participants in the Glasgow University alumni cohort study
BACKGROUND: Recent large-scale studies suggest that obesity and overweight may confer protection against future dementia. This observation could, however, be generated by reverse causality. That is, weight loss in the incipient phase of dementia ascribed to diminished self-care, including sub-optimal nutrition, would have the effect of generating such an inverse association. One approach to circumventing this problem would be to measure weight in a population which is young enough to be free of the symptoms of dementia which is then followed up for dementia occurrence over many decades. METHODS: In a prospective cohort study, body mass index, and other potential risk factors, were measured in 9547 male university undergraduates (mean age 20.5Â years) in 1948-68 who were then linked to national mortality registers. RESULTS: Of 2537 deaths over a mean of 50.6Â years follow up, 140 were ascribed to dementia. There was no association between overweight and future dementia deaths (age-adjusted hazard ratio; 95Â % confidence interval: 0.93; 0.49, 1.79). CONCLUSION: In this cohort study of former university students, being overweight in youth did not confer protection against later dementia death
Sifting for Sapphires: Systematic Selection of Tidal Disruption Events in iPTF
We present results from a systematic selection of tidal disruption events
(TDEs) in a wide-area (4800~deg), band, Intermediate Palomar
Transient Factory (iPTF) experiment. Our selection targets typical
optically-selected TDEs: bright (60\% flux increase) and blue transients
residing in the center of red galaxies. Using photometric selection criteria to
down-select from a total of 493 nuclear transients to a sample of 26 sources,
we then use follow-up UV imaging with the Neil Gehrels Swift Telescope,
ground-based optical spectroscopy, and light curve fitting to classify them as
14 Type Ia supernovae (SNe Ia), 9 highly variable active galactic nuclei
(AGNs), 2 confirmed TDEs, and 1 potential core-collapse supernova. We find it
possible to filter AGNs by employing a more stringent transient color cut ( 0.2 mag); further, UV imaging is the best discriminator for filtering
SNe, since SNe Ia can appear as blue, optically, as TDEs in their early phases.
However, when UV-optical color is unavailable, higher precision astrometry can
also effectively reduce SNe contamination in the optical. Our most stringent
optical photometric selection criteria yields a 4.5:1 contamination rate,
allowing for a manageable number of TDE candidates for complete spectroscopic
follow-up and real-time classification in the ZTF era. We measure a TDE per
galaxy rate of 1.7 10 gal yr (90\%
CL in Poisson statistics). This does not account for TDEs outside our selection
criteria, thus may not reflect the total TDE population, which is yet to be
fully mapped.Comment: 24 pages, 21 figures. Accepted for publication in the Astrophysical
Journal Supplement Serie
Big data and data repurposing – using existing data to answer new questions in vascular dementia research
Introduction:
Traditional approaches to clinical research have, as yet, failed to provide effective treatments for vascular dementia (VaD). Novel approaches to collation and synthesis of data may allow for time and cost efficient hypothesis generating and testing. These approaches may have particular utility in helping us understand and treat a complex condition such as VaD.
Methods:
We present an overview of new uses for existing data to progress VaD research. The overview is the result of consultation with various stakeholders, focused literature review and learning from the group’s experience of successful approaches to data repurposing. In particular, we benefitted from the expert discussion and input of delegates at the 9th International Congress on Vascular Dementia (Ljubljana, 16-18th October 2015).
Results:
We agreed on key areas that could be of relevance to VaD research: systematic review of existing studies; individual patient level analyses of existing trials and cohorts and linking electronic health record data to other datasets. We illustrated each theme with a case-study of an existing project that has utilised this approach.
Conclusions:
There are many opportunities for the VaD research community to make better use of existing data. The volume of potentially available data is increasing and the opportunities for using these resources to progress the VaD research agenda are exciting. Of course, these approaches come with inherent limitations and biases, as bigger datasets are not necessarily better datasets and maintaining rigour and critical analysis will be key to optimising data use
Volume Expansion of Swiss-Cheese Universe
In order to investigate the effect of inhomogeneities on the volume expansion
of the universe, we study modified Swiss-Cheese universe model. Since this
model is an exact solution of Einstein equations, we can get an insight into
non-linear dynamics of inhomogeneous universe from it. We find that
inhomogeneities make the volume expansion slower than that of the background
Einstein-de Sitter universe when those can be regarded as small fluctuations in
the background universe. This result is consistent with the previous studies
based on the second order perturbation analysis. On the other hand, if the
inhomogeneities can not be treated as small perturbations, the volume expansion
of the universe depends on the type of fluctuations. Although the volume
expansion rate approaches to the background value asymptotically, the volume
itself can be finally arbitrarily smaller than the background one and can be
larger than that of the background but there is an upper bound on it.Comment: 22 pages, 7 figures, to be submitted to Phys. Rev.
Improving Incremental Balance in the GSI 3DVAR Analysis System
The Gridpoint Statistical Interpolation (GSI) analysis system is a unified global/regional 3DVAR analysis code that has been under development for several years at the National Centers for Environmental Prediction (NCEP)/Environmental Modeling Center. It has recently been implemented into operations at NCEP in both the global and North American data assimilation systems (GDAS and NDAS). An important aspect of this development has been improving the balance of the analysis produced by GSI. The improved balance between variables has been achieved through the inclusion of a Tangent Linear Normal Mode Constraint (TLNMC). The TLNMC method has proven to be very robust and effective. The TLNMC as part of the global GSI system has resulted in substantial improvement in data assimilation both at NCEP and at the NASA Global Modeling and Assimilation Office (GMAO)
Epidermal Growth Factor–PEG Functionalized PAMAM-Pentaethylenehexamine Dendron for Targeted Gene Delivery Produced by Click Chemistry
Aim of this study was the site-specific conjugation of an epidermal growth factor (EGF)-polyethylene glycol (PEG) chain by click chemistry onto a poly(amido amine) (PAMAM) dendron, as a key step toward defined multifunctional carriers for targeted gene delivery. For this purpose, at first propargyl amine cored PAMAM dendrons with ester ends were synthesized. The chain terminal ester groups were then modified by oligoamines with different secondary amino densities. The oligoamine-modified PAMAM dendrons were well biocompatible, as demonstrated in cytotoxicity assays. Among the different oligoamine-modified dendrons, PAMAM-pentaethylenehexamine (PEHA) dendron polyplexes displayed the best gene transfer ability. Conjugation of PAMAM-PEHA dendron with PEG spacer was conducted via click reaction, which was performed before amidation with PEHA. The resultant PEG-PAMAM-PEHA copolymer was then coupled with EGF ligand. pDNA transfections in HuH-7 hepatocellular carcinoma cells showed a 10-fold higher efficiency with the polyplexes containing conjugated EGF as compared to the ligand-free ones, demonstrating the concept of ligand targeting. Overall gene transfer efficiencies, however, were moderate, suggesting that additional measures for overcoming subsequent intracellular bottlenecks in delivery have to be taken
Massively Parallel Sequencing of Human Urinary Exosome/Microvesicle RNA Reveals a Predominance of Non-Coding RNA
Intact RNA from exosomes/microvesicles (collectively referred to as microvesicles) has sparked much interest as potential biomarkers for the non-invasive analysis of disease. Here we use the Illumina Genome Analyzer to determine the comprehensive array of nucleic acid reads present in urinary microvesicles. Extraneous nucleic acids were digested using RNase and DNase treatment and the microvesicle inner nucleic acid cargo was analyzed with and without DNase digestion to examine both DNA and RNA sequences contained in microvesicles. Results revealed that a substantial proportion (∼87%) of reads aligned to ribosomal RNA. Of the non-ribosomal RNA sequences, ∼60% aligned to non-coding RNA and repeat sequences including LINE, SINE, satellite repeats, and RNA repeats (tRNA, snRNA, scRNA and srpRNA). The remaining ∼40% of non-ribosomal RNA reads aligned to protein coding genes and splice sites encompassing approximately 13,500 of the known 21,892 protein coding genes of the human genome. Analysis of protein coding genes specific to the renal and genitourinary tract revealed that complete segments of the renal nephron and collecting duct as well as genes indicative of the bladder and prostate could be identified. This study reveals that the entire genitourinary system may be mapped using microvesicle transcript analysis and that the majority of non-ribosomal RNA sequences contained in microvesicles is potentially functional non-coding RNA, which play an emerging role in cell regulation
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