355 research outputs found
Intercalation-enhanced electric polarization and chain formation of nano-layered particles
Microscopy observations show that suspensions of synthetic and natural
nano-layered smectite clay particles submitted to a strong external electric
field undergo a fast and extended structuring. This structuring results from
the interaction between induced electric dipoles, and is only possible for
particles with suitable polarization properties. Smectite clay colloids are
observed to be particularly suitable, in contrast to similar suspensions of a
non-swelling clay. Synchrotron X-ray scattering experiments provide the
orientation distributions for the particles. These distributions are understood
in terms of competing (i) homogenizing entropy and (ii) interaction between the
particles and the local electric field; they show that clay particles polarize
along their silica sheet. Furthermore, a change in the platelet separation
inside nano-layered particles occurs under application of the electric field,
indicating that intercalated ions and water molecules play a role in their
electric polarization. The resulting induced dipole is structurally attached to
the particle, and this causes particles to reorient and interact, resulting in
the observed macroscopic structuring. The macroscopic properties of these
electro-rheological smectite suspensions may be tuned by controlling the nature
and quantity of the intercalated species, at the nanoscale.Comment: 7 pages, 5 figure
Scattering statistics of rock outcrops: Model-data comparisons and Bayesian inference using mixture distributions
The probability density function of the acoustic field amplitude scattered by
the seafloor was measured in a rocky environment off the coast of Norway using
a synthetic aperture sonar system, and is reported here in terms of the
probability of false alarm. Interpretation of the measurements focused on
finding appropriate class of statistical models (single versus two-component
mixture models), and on appropriate models within these two classes. It was
found that two-component mixture models performed better than single models.
The two mixture models that performed the best (and had a basis in the physics
of scattering) were a mixture between two K distributions, and a mixture
between a Rayleigh and generalized Pareto distribution. Bayes' theorem was used
to estimate the probability density function of the mixture model parameters.
It was found that the K-K mixture exhibits significant correlation between its
parameters. The mixture between the Rayleigh and generalized Pareto
distributions also had significant parameter correlation, but also contained
multiple modes. We conclude that the mixture between two K distributions is the
most applicable to this dataset.Comment: 15 pages, 7 figures, Accepted to the Journal of the Acoustical
Society of Americ
Potential Antiviral Options against SARS-CoV-2 Infection
As of June 2020, the number of people infected with severe acute respiratory coronavirus 2 (SARS-CoV-2) continues to skyrocket, with more than 6.7 million cases worldwide. Both the World Health Organization (WHO) and United Nations (UN) has highlighted the need for better control of SARS-CoV-2 infections. However, developing novel virus-specific vaccines, monoclonal antibodies and antiviral drugs against SARS-CoV-2 can be time-consuming and costly. Convalescent sera and safe-in-man broad-spectrum antivirals (BSAAs) are readily available treatment options. Here, we developed a neutralization assay using SARS-CoV-2 strain and Vero-E6 cells. We identified the most potent sera from recovered patients for the treatment of SARS-CoV-2-infected patients. We also screened 136 safe-in-man broad-spectrum antivirals against the SARS-CoV-2 infection in Vero-E6 cells and identified nelfinavir, salinomycin, amodiaquine, obatoclax, emetine and homoharringtonine. We found that a combination of orally available virus-directed nelfinavir and host-directed amodiaquine exhibited the highest synergy. Finally, we developed a website to disseminate the knowledge on available and emerging treatments of COVID-19
Characterization and Comparison of 2 Distinct Epidemic Community-Associated Methicillin-Resistant Staphylococcus aureus Clones of ST59 Lineage.
Sequence type (ST) 59 is an epidemic lineage of community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) isolates. Taiwanese CA-MRSA isolates belong to ST59 and can be grouped into 2 distinct clones, a virulent Taiwan clone and a commensal Asian-Pacific clone. The Taiwan clone carries the Panton-Valentine leukocidin (PVL) genes and the staphylococcal chromosomal cassette mec (SCCmec) VT, and is frequently isolated from patients with severe disease. The Asian-Pacific clone is PVL-negative, carries SCCmec IV, and a frequent colonizer of healthy children. Isolates of both clones were characterized by their ability to adhere to respiratory A549 cells, cytotoxicity to human neutrophils, and nasal colonization of a murine and murine sepsis models. Genome variation was determined by polymerase chain reaction of selected virulence factors and by multi-strain whole genome microarray. Additionally, the expression of selected factors was compared between the 2 clones. The Taiwan clone showed a much higher cytotoxicity to the human neutrophils and caused more severe septic infections with a high mortality rate in the murine model. The clones were indistinguishable in their adhesion to A549 cells and persistence of murine nasal colonization. The microarray data revealed that the Taiwan clone had lost the ø3-prophage that integrates into the β-hemolysin gene and includes staphylokinase- and enterotoxin P-encoding genes, but had retained the genes for human immune evasion, scn and chps. Production of the virulence factors did not differ significantly in the 2 clonal groups, although more α-toxin was expressed in Taiwan clone isolates from pneumonia patients. In conclusion, the Taiwan CA-MRSA clone was distinguished by enhanced virulence in both humans and an animal infection model. The evolutionary acquisition of PVL, the higher expression of α-toxin, and possibly the loss of a large portion of the β-hemolysin-converting prophage likely contribute to its higher pathogenic potential than the Asian-Pacific clone
A Reduction in Ribonucleotide Reductase Activity Slows Down the Chromosome Replication Fork but Does Not Change Its Localization
BACKGROUND:It has been proposed that the enzymes of nucleotide biosynthesis may be compartmentalized or concentrated in a structure affecting the organization of newly replicated DNA. Here we have investigated the effect of changes in ribonucleotide reductase (RNR) activity on chromosome replication and organization of replication forks in Escherichia coli. METHODOLOGY/PRINCIPAL FINDINGS:Reduced concentrations of deoxyribonucleotides (dNTPs) obtained by reducing the activity of wild type RNR by treatment with hydroxyurea or by mutation, resulted in a lengthening of the replication period. The replication fork speed was found to be gradually reduced proportionately to moderate reductions in nucleotide availability. Cells with highly extended C periods showed a "delay" in cell division i.e. had a higher cell mass. Visualization of SeqA structures by immunofluorescence indicated no change in organization of the new DNA upon moderate limitation of RNR activity. Severe nucleotide limitation led to replication fork stalling and reversal. Well defined SeqA structures were not found in situations of extensive replication fork repair. In cells with stalled forks obtained by UV irradiation, considerable DNA compaction was observed, possibly indicating a reorganization of the DNA into a "repair structure" during the initial phase of the SOS response. CONCLUSION/SIGNIFICANCE:The results indicate that the replication fork is slowed down in a controlled manner during moderate nucleotide depletion and that a change in the activity of RNR does not lead to a change in the organization of newly replicated DNA. Control of cell division but not control of initiation was affected by the changes in replication elongation
A systematic analysis of host factors reveals a Med23-interferon-λ regulatory axis against herpes simplex virus type 1 replication
Herpes simplex virus type 1 (HSV-1) is a neurotropic virus causing vesicular oral or genital skin lesions, meningitis and other diseases particularly harmful in immunocompromised individuals. To comprehensively investigate the complex interaction between HSV-1 and its host we combined two genome-scale screens for host factors (HFs) involved in virus replication. A yeast two-hybrid screen for protein interactions and a RNA interference (RNAi) screen with a druggable genome small interfering RNA (siRNA) library confirmed existing and identified novel HFs which functionally influence HSV-1 infection. Bioinformatic analyses found the 358 HFs were enriched for several pathways and multi-protein complexes. Of particular interest was the identification of Med23 as a strongly anti-viral component of the largely pro-viral Mediator complex, which links specific transcription factors to RNA polymerase II. The anti-viral effect of Med23 on HSV-1 replication was confirmed in gain-of-function gene overexpression experiments, and this inhibitory effect was specific to HSV-1, as a range of other viruses including Vaccinia virus and Semliki Forest virus were unaffected by Med23 depletion. We found Med23 significantly upregulated expression of the type III interferon family (IFN-λ) at the mRNA and protein level by directly interacting with the transcription factor IRF7. The synergistic effect of Med23 and IRF7 on IFN-λ induction suggests this is the major transcription factor for IFN-λ expression. Genotypic analysis of patients suffering recurrent orofacial HSV-1 outbreaks, previously shown to be deficient in IFN-λ secretion, found a significant correlation with a single nucleotide polymorphism in the IFN-λ3 (IL28b) promoter strongly linked to Hepatitis C disease and treatment outcome. This paper describes a link between Med23 and IFN-λ, provides evidence for the crucial role of IFN-λ in HSV-1 immune control, and highlights the power of integrative genome-scale approaches to identify HFs critical for disease progression and outcome
A new resorbable device for ligation of blood vessels - A pilot study
<p>Abstract</p> <p>Background</p> <p>During surgery, controlled haemostasis to prevent blood loss is vital for a successful outcome. It can be difficult to ligate vessels located deep in the abdomen. A device that is easy to use and enables secure ligatures could be beneficial. Cable ties made of nylon have been used for ligation but the non-resorbable material caused tissue reactions. The objective of this study was to use a resorbable material to construct a device with a self-locking mechanism and to test its mechanical strength and ligation efficiency.</p> <p>Methods</p> <p>The device was manufactured by injection moulding of polydioxanone, a resorbable polymer used for suture materials. Polydioxanone with inherent viscosities of 1.9 dL/g and 1.3 dL/g were tested. The device consisted of a perforated flexible band which could be pulled through a case with a locking mechanism. After a first version of the device had been tested, some improvements were made. The locking case was downsized, corners were rounded off, the band was made thicker and the mould was redesigned to produce longer devices. Tensile tests were performed with the second version.</p> <p>The first version of the device was used to ligate the ovarian pedicle in a euthanized dog and to test echogenicity of the device with ultrasound. Compression of vessels of the ovarian pedicle was examined by histology. Both versions of the device were tested for haemostasis of and tissue grip on renal arteries in six anaesthetised pigs.</p> <p>Results</p> <p>The tensile strength of the flexible band of the devices with inherent viscosity of 1.9 dL/g was 50.1 ± 5.5 N (range 35.2-62.9 N, <it>n </it>= 11) and the devices with inherent viscosity of 1.3 dL/g had a tensile strength of 39.8 ± 8.1 N (range 18.6-54.2 N, <it>n </it>= 11). Injection moulding of the polymer with lower inherent viscosity resulted in a longer flow distance.</p> <p>Both versions of the device had an effective tissue grip and complete haemostasis of renal arteries was verified. The device attached to the ovarian pedicle could be seen with ultrasound, and vessel compression and occlusion were verified by histology.</p> <p>Conclusions</p> <p>Tests of functionality of the device showed complete haemostasis and good tissue grip. Devices with a band of sufficient length were easily applied and tightened in tissue.</p
Multiwavelength studies of MHD waves in the solar chromosphere: An overview of recent results
The chromosphere is a thin layer of the solar atmosphere that bridges the
relatively cool photosphere and the intensely heated transition region and
corona. Compressible and incompressible waves propagating through the
chromosphere can supply significant amounts of energy to the interface region
and corona. In recent years an abundance of high-resolution observations from
state-of-the-art facilities have provided new and exciting ways of
disentangling the characteristics of oscillatory phenomena propagating through
the dynamic chromosphere. Coupled with rapid advancements in
magnetohydrodynamic wave theory, we are now in an ideal position to thoroughly
investigate the role waves play in supplying energy to sustain chromospheric
and coronal heating. Here, we review the recent progress made in
characterising, categorising and interpreting oscillations manifesting in the
solar chromosphere, with an impetus placed on their intrinsic energetics.Comment: 48 pages, 25 figures, accepted into Space Science Review
Constitutional patriotism
Constitutional patriotism is a political theory that seeks to provide an explanation for the sense of ownership that most individuals have towards their national constitutional system. Specifically, constitutional patriotism assumes that free-thinking individuals involved in a discussion over the common good will reach an agreement that is perceived, at least by those involved in the debate, as having normative value. The awareness that such a deliberative process has historically been a part of the constitutional system also induces a sense of ownership of past historical accommodations of constitutional principles. The shared perception of being part of historically grounded institutions within a deliberative democracy is sometimes called the ‘normative surplus effect’ or ‘normative spill-over effect’ of the deliberative process. The theory, in its current form, was proposed by Jürgen Habermas and Jean-Werner Müller.
Debates over the common good might take place informally or within the state’s institutions. Pell-mell informal debates, with few exceptions, have a limited effect on amending constitutional norms. Yet, the prerogative to openly discuss laws and policies legitimised by constitutional norms is normally sufficient to develop an inner sense of belonging to a constitutional system. Deliberative debates within public institutions (e.g. parliaments and courts) are more likely to change the functioning of a constitutional system, but they are, by way of comparison to informal political discussions, normally constrained by the system of rules that regulate representative democracy and the administration of justice. Thus, the theory of constitutional patriotism provides an explanatory model for the historical development of a democratic constitutional system.
As one of the most persuasive explanatory theories of modern pluralist democracy, constitutional patriotism has attracted a series of well-articulated critiques. It has been suggested, for instance, that constitutional patriotism might not provide a plausible model of social integration for international organisations such as the European Union (EU). In this essay, I will provide an overview of the theory and a selection of its critiques
Domain-Domain Interactions Underlying Herpesvirus-Human Protein-Protein Interaction Networks
Protein-domains play an important role in mediating protein-protein interactions. Furthermore, the same domain-pairs mediate different interactions in different contexts and in various organisms, and therefore domain-pairs are considered as the building blocks of interactome networks. Here we extend these principles to the host-virus interface and find the domain-pairs that potentially mediate human-herpesvirus interactions. Notably, we find that the same domain-pairs used by other organisms for mediating their interactions underlie statistically significant fractions of human-virus protein inter-interaction networks. Our analysis shows that viral domains tend to interact with human domains that are hubs in the human domain-domain interaction network. This may enable the virus to easily interfere with a variety of mechanisms and processes involving various and different human proteins carrying the relevant hub domain. Comparative genomics analysis provides hints at a molecular mechanism by which the virus acquired some of its interacting domains from its human host
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