1,380 research outputs found
Towards an understanding of hole superconductivity
From the very beginning K. Alex M\"uller emphasized that the materials he and
George Bednorz discovered in 1986 were superconductors. Here I would
like to share with him and others what I believe to be key reason for why
high cuprates as well as all other superconductors are hole
superconductors, which I only came to understand a few months ago. This paper
is dedicated to Alex M\"uller on the occasion of his 90th birthday.Comment: Dedicated to Alex M\"uller on the Occasion of his 90th Birthday.
arXiv admin note: text overlap with arXiv:1703.0977
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
Approximate probabilistic verification of hybrid systems
Hybrid systems whose mode dynamics are governed by non-linear ordinary
differential equations (ODEs) are often a natural model for biological
processes. However such models are difficult to analyze. To address this, we
develop a probabilistic analysis method by approximating the mode transitions
as stochastic events. We assume that the probability of making a mode
transition is proportional to the measure of the set of pairs of time points
and value states at which the mode transition is enabled. To ensure a sound
mathematical basis, we impose a natural continuity property on the non-linear
ODEs. We also assume that the states of the system are observed at discrete
time points but that the mode transitions may take place at any time between
two successive discrete time points. This leads to a discrete time Markov chain
as a probabilistic approximation of the hybrid system. We then show that for
BLTL (bounded linear time temporal logic) specifications the hybrid system
meets a specification iff its Markov chain approximation meets the same
specification with probability . Based on this, we formulate a sequential
hypothesis testing procedure for verifying -approximately- that the Markov
chain meets a BLTL specification with high probability. Our case studies on
cardiac cell dynamics and the circadian rhythm indicate that our scheme can be
applied in a number of realistic settings
Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB)
BACKGROUND:Cutaneous leishmaniasis (CL) is a neglected tropical disease caused by protozoan parasites of the genus Leishmania. CL causes enormous suffering in many countries worldwide. There is no licensed vaccine against CL, and the chemotherapy options show limited efficacy and high toxicity. Localization of the parasites inside host cells is a barrier to most standard chemo- and immune-based interventions. Hence, novel drugs, which are safe, effective and readily accessible to third-world countries and/or drug delivery technologies for effective CL treatments are desperately needed. METHODOLOGY/PRINCIPAL FINDINGS:Here we evaluated the antileishmanial properties and delivery potential of polyhexamethylene biguanide (PHMB; polyhexanide), a widely used antimicrobial and wound antiseptic, in the Leishmania model. PHMB showed an inherent antileishmanial activity at submicromolar concentrations. Our data revealed that PHMB kills Leishmania major (L. major) via a dual mechanism involving disruption of membrane integrity and selective chromosome condensation and damage. PHMB's DNA binding and host cell entry properties were further exploited to improve the delivery and immunomodulatory activities of unmethylated cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODN). PHMB spontaneously bound CpG ODN, forming stable nanopolyplexes that enhanced uptake of CpG ODN, potentiated antimicrobial killing and reduced host cell toxicity of PHMB. CONCLUSIONS:Given its low cost and long history of safe topical use, PHMB holds promise as a drug for CL therapy and delivery vehicle for nucleic acid immunomodulators
MRI of the lung (3/3)-current applications and future perspectives
BACKGROUND: MRI of the lung is recommended in a number of clinical indications. Having a non-radiation alternative is particularly attractive in children and young subjects, or pregnant women. METHODS: Provided there is sufficient expertise, magnetic resonance imaging (MRI) may be considered as the preferential modality in specific clinical conditions such as cystic fibrosis and acute pulmonary embolism, since additional functional information on respiratory mechanics and regional lung perfusion is provided. In other cases, such as tumours and pneumonia in children, lung MRI may be considered an alternative or adjunct to other modalities with at least similar diagnostic value. RESULTS: In interstitial lung disease, the clinical utility of MRI remains to be proven, but it could provide additional information that will be beneficial in research, or at some stage in clinical practice. Customised protocols for chest imaging combine fast breath-hold acquisitions from a "buffet" of sequences. Having introduced details of imaging protocols in previous articles, the aim of this manuscript is to discuss the advantages and limitations of lung MRI in current clinical practice. CONCLUSION: New developments and future perspectives such as motion-compensated imaging with self-navigated sequences or fast Fourier decomposition MRI for non-contrast enhanced ventilation- and perfusion-weighted imaging of the lung are discussed. Main Messages • MRI evolves as a third lung imaging modality, combining morphological and functional information. • It may be considered first choice in cystic fibrosis and pulmonary embolism of young and pregnant patients. • In other cases (tumours, pneumonia in children), it is an alternative or adjunct to X-ray and CT. • In interstitial lung disease, it serves for research, but the clinical value remains to be proven. • New users are advised to make themselves familiar with the particular advantages and limitations
Management of venous thrombosis in fibular free osseomusculocutaneous flaps used for mandibular reconstruction: clinical techniques and treatment considerations
<p>Abstract</p> <p>Background</p> <p>Mandibular reconstruction by means of fibula transplants is the standard therapy for severe bone loss after subtotal mandibulectomy. Venous failure still represents the most common complication in free flap surgery. We present the injection of heparine into the arterial pedicle as modification of the revising both anastomoses in these cases and illustrate the application with a clinical case example.</p> <p>Methods</p> <p>Methods consist of immediate revision surgery with clot removal, heparin perfusion by direct injection in the arterial vessel of the pedicle, subsequent high dose low-molecular weight heparin therapy, and leeches. After 6 hours postoperatively, images of early flap recovery show first sings of recovery by fading livid skin color.</p> <p>Results</p> <p>The application of this technique in a patient with venous thrombosis resulted in the complete recovery of the flap 60 hours postoperatively. Other cases achieved similar success without additional lysis Therapy or revision of the arterial anastomosis.</p> <p>Conclusion</p> <p>Rescue of fibular flaps is possible even in patients with massive thrombosis if surgical revision is done quickly.</p
The Hubbard model within the equations of motion approach
The Hubbard model has a special role in Condensed Matter Theory as it is
considered as the simplest Hamiltonian model one can write in order to describe
anomalous physical properties of some class of real materials. Unfortunately,
this model is not exactly solved except for some limits and therefore one
should resort to analytical methods, like the Equations of Motion Approach, or
to numerical techniques in order to attain a description of its relevant
features in the whole range of physical parameters (interaction, filling and
temperature). In this manuscript, the Composite Operator Method, which exploits
the above mentioned analytical technique, is presented and systematically
applied in order to get information about the behavior of all relevant
properties of the model (local, thermodynamic, single- and two- particle ones)
in comparison with many other analytical techniques, the above cited known
limits and numerical simulations. Within this approach, the Hubbard model is
shown to be also capable to describe some anomalous behaviors of the cuprate
superconductors.Comment: 232 pages, more than 300 figures, more than 500 reference
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
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