1,696 research outputs found
Signaling Modification by GPCR Heteromer and Its Implication on X-Linked Nephrogenic Diabetes Insipidus
published_or_final_versio
Epidemiological and Evolutionary Dynamics of Influenza B Viruses in Malaysia, 2012-2014
Epidemiological and evolutionary dynamics of influenza B Victoria and Yamagata lineages remained poorly understood in the tropical Southeast Asia region, despite causing seasonal outbreaks worldwide. From 2012-2014, nasopharyngeal swab samples collected from outpatients experiencing acute upper respiratory tract infection symptoms in Kuala Lumpur, Malaysia, were screened for influenza viruses using a multiplex RT-PCR assay. Among 2,010/3,935 (51.1%) patients infected with at least one respiratory virus, 287 (14.3%) and 183 (9.1%) samples were tested positive for influenza A and B viruses, respectively. Influenza-positive cases correlate significantly with meteorological factors-total amount of rainfall, relative humidity, number of rain days, ground temperature and particulate matter (PM10). Phylogenetic reconstruction of haemagglutinin (HA) gene from 168 influenza B viruses grouped them into Yamagata Clade 3 (65, 38.7%), Yamagata Clade 2 (48, 28.6%) and Victoria Clade 1 (55, 32.7%). With neuraminidase (NA) phylogeny, 30 intra-clade (29 within Yamagata Clade 3, 1 within Victoria Clade 1) and 1 inter-clade (Yamagata Clade 2-HA/Yamagata Clade 3-NA) reassortants were identified. Study of virus temporal dynamics revealed a lineage shift from Victoria to Yamagata (2012-2013), and a clade shift from Yamagata Clade 2 to Clade 3 (2013-2014). Yamagata Clade 3 predominating in 2014 consisted of intra-clade reassortants that were closely related to a recent WHO vaccine candidate strain (B/Phuket/3073/2013), with the reassortment event occurred approximately 2 years ago based on Bayesian molecular clock estimation. Malaysian Victoria Clade 1 viruses carried H274Y substitution in the active site of neuraminidase, which confers resistance to oseltamivir. Statistical analyses on clinical and demographic data showed Yamagata-infected patients were older and more likely to experience headache while Victoria-infected patients were more likely to experience nasal congestion and sore throat. This study describes the evolution of influenza B viruses in Malaysia and highlights the importance of continuous surveillance for better vaccination policy in this region.published_or_final_versio
Heavy fermions and two loop electroweak corrections to
Applying effective Lagrangian method and on-shell scheme, we analyze the
electroweak corrections to the rare decay from some
special two loop diagrams in which a closed heavy fermion loop is attached to
the virtual charged gauge bosons or Higgs. At the decoupling limit where the
virtual fermions in inner loop are much heavier than the electroweak scale, we
verify the final results satisfying the decoupling theorem explicitly when the
interactions among Higgs and heavy fermions do not contain the nondecoupling
couplings. Adopting the universal assumptions on the relevant couplings and
mass spectrum of new physics, we find that the relative corrections from those
two loop diagrams to the SM theoretical prediction on the branching ratio of
can reach 5% as the energy scale of new physics
GeV.Comment: 30 pages,4 figure
A gentle introduction to the functional renormalization group: the Kondo effect in quantum dots
The functional renormalization group provides an efficient description of the
interplay and competition of correlations on different energy scales in
interacting Fermi systems. An exact hierarchy of flow equations yields the
gradual evolution from a microscopic model Hamiltonian to the effective action
as a function of a continuously decreasing energy cutoff. Practical
implementations rely on suitable truncations of the hierarchy, which capture
nonuniversal properties at higher energy scales in addition to the universal
low-energy asymptotics. As a specific example we study transport properties
through a single-level quantum dot coupled to Fermi liquid leads. In
particular, we focus on the temperature T=0 gate voltage dependence of the
linear conductance. A comparison with exact results shows that the functional
renormalization group approach captures the broad resonance plateau as well as
the emergence of the Kondo scale. It can be easily extended to more complex
setups of quantum dots.Comment: contribution to Les Houches proceedings 2006, Springer styl
Knockout studies reveal an important role of <i>plasmodium</i> lipoic acid protein ligase a1 for asexual blood stage parasite survival
Lipoic acid (LA) is a dithiol-containing cofactor that is essential for the function of a-keto acid dehydrogenase complexes. LA acts as a reversible acyl group acceptor and 'swinging arm' during acyl-coenzyme A formation. The cofactor is post-translationally attached to the acyl-transferase subunits of the multienzyme complexes through the action of octanoyl (lipoyl): <i>N</i>-octanoyl (lipoyl) transferase (LipB) or lipoic acid protein ligases (LplA). Remarkably, apicomplexan parasites possess LA biosynthesis as well as scavenging pathways and the two pathways are distributed between mitochondrion and a vestigial organelle, the apicoplast. The apicoplast-specific LipB is dispensable for parasite growth due to functional redundancy of the parasite's lipoic acid/octanoic acid ligases/transferases. In this study, we show that <i>LplA1</i> plays a pivotal role during the development of the erythrocytic stages of the malaria parasite. Gene disruptions in the human malaria parasite <i>P.falciparum</i> consistently were unsuccessful while in the rodent malaria model parasite <i>P. berghei</i> the <i>LplA1</i> gene locus was targeted by knock-in and knockout constructs. However, the <i>LplA1</i> <sup>(-)</sup> mutant could not be cloned suggesting a critical role of LplA1 for asexual parasite growth <i>in vitro</i> and <i>in vivo</i>. These experimental genetics data suggest that lipoylation during expansion in red blood cells largely occurs through salvage from the host erythrocytes and subsequent ligation of LA to the target proteins of the malaria parasite
Can Antiviral Drugs Contain Pandemic Influenza Transmission?
Antiviral drugs dispensed during the 2009 influenza pandemic generally failed to
contain transmission. This poses the question of whether preparedness for a
future pandemic should include plans to use antiviral drugs to mitigate
transmission
Detecting undiagnosed atrial fibrillation in UK primary care: Validation of a machine learning prediction algorithm in a retrospective cohort study
Aims To evaluate the ability of a machine learning algorithm to identify patients at high risk of atrial fibrillation in primary care. Methods A retrospective cohort study was undertaken using the DISCOVER registry to validate an algorithm developed using a Clinical Practice Research Datalink (CPRD) dataset. The validation dataset included primary care patients in London, England aged ≥30 years from 1 January 2006 to 31 December 2013, without a diagnosis of atrial fibrillation in the prior 5 years. Algorithm performance metrics were sensitivity, specificity, positive predictive value, negative predictive value (NPV) and number needed to screen (NNS). Subgroup analysis of patients aged ≥65 years was also performed. Results Of 2,542,732 patients in DISCOVER, the algorithm identified 604,135 patients suitable for risk assessment. Of these, 3.0% (17,880 patients) had a diagnosis of atrial fibrillation recorded before study end. The area under the curve of the receiver operating characteristic was 0.87, compared with 0.83 in algorithm development. The NNS was nine patients, matching the CPRD cohort. In patients aged ≥30 years, the algorithm correctly identified 99.1% of patients who did not have atrial fibrillation (NPV) and 75.0% of true atrial fibrillation cases (sensitivity). Among patients aged ≥65 years (n = 117,965), the NPV was 96.7% with 91.8% sensitivity. Conclusions This atrial fibrillation risk prediction algorithm, based on machine learning methods, identified patients at highest risk of atrial fibrillation. It performed comparably in a large, real-world population-based cohort and the developmental registry cohort. If implemented in primary care, the algorithm could be an effective tool for narrowing the population who would benefit from atrial fibrillation screening in the United Kingdom
The role of multiple marks in epigenetic silencing and the emergence of a stable bivalent chromatin state
We introduce and analyze a minimal model of epigenetic silencing in budding
yeast, built upon known biomolecular interactions in the system. Doing so, we
identify the epigenetic marks essential for the bistability of epigenetic
states. The model explicitly incorporates two key chromatin marks, namely H4K16
acetylation and H3K79 methylation, and explores whether the presence of
multiple marks lead to a qualitatively different systems behavior. We find that
having both modifications is important for the robustness of epigenetic
silencing. Besides the silenced and transcriptionally active fate of chromatin,
our model leads to a novel state with bivalent (i.e., both active and
silencing) marks under certain perturbations (knock-out mutations, inhibition
or enhancement of enzymatic activity). The bivalent state appears under several
perturbations and is shown to result in patchy silencing. We also show that the
titration effect, owing to a limited supply of silencing proteins, can result
in counter-intuitive responses. The design principles of the silencing system
is systematically investigated and disparate experimental observations are
assessed within a single theoretical framework. Specifically, we discuss the
behavior of Sir protein recruitment, spreading and stability of silenced
regions in commonly-studied mutants (e.g., sas2, dot1) illuminating the
controversial role of Dot1 in the systems biology of yeast silencing.Comment: Supplementary Material, 14 page
Solitary waves in the Nonlinear Dirac Equation
In the present work, we consider the existence, stability, and dynamics of
solitary waves in the nonlinear Dirac equation. We start by introducing the
Soler model of self-interacting spinors, and discuss its localized waveforms in
one, two, and three spatial dimensions and the equations they satisfy. We
present the associated explicit solutions in one dimension and numerically
obtain their analogues in higher dimensions. The stability is subsequently
discussed from a theoretical perspective and then complemented with numerical
computations. Finally, the dynamics of the solutions is explored and compared
to its non-relativistic analogue, which is the nonlinear Schr{\"o}dinger
equation. A few special topics are also explored, including the discrete
variant of the nonlinear Dirac equation and its solitary wave properties, as
well as the PT-symmetric variant of the model
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