170 research outputs found
TBA for non-perturbative moduli spaces
Recently, an exact description of instanton corrections to the moduli spaces
of 4d N=2 supersymmetric gauge theories compactified on a circle and Calabi-Yau
compactifications of Type II superstring theories was found. The equations
determining the instanton contributions turn out to have the form of
Thermodynamic Bethe Ansatz. We explore further this relation and, in
particular, we identify the contact potential of quaternionic string moduli
space with the free energy of the integrable system and the Kahler potential of
the gauge theory moduli space with the Yang-Yang functional. We also show that
the corresponding S-matrix satisfies all usual constraints of 2d integrable
models, including crossing and bootstrap, and derive the associated Y-system.
Surprisingly, in the simplest case the Y-system is described by the MacMahon
function relevant for crystal melting and topological strings.Comment: 25 pages, 1 figur
Brezin-Gross-Witten model as "pure gauge" limit of Selberg integrals
The AGT relation identifies the Nekrasov functions for various N=2 SUSY gauge
theories with the 2d conformal blocks, which possess explicit Dotsenko-Fateev
matrix model (beta-ensemble) representations the latter being polylinear
combinations of Selberg integrals. The "pure gauge" limit of these matrix
models is, however, a non-trivial multiscaling large-N limit, which requires a
separate investigation. We show that in this pure gauge limit the Selberg
integrals turn into averages in a Brezin-Gross-Witten (BGW) model. Thus, the
Nekrasov function for pure SU(2) theory acquires a form very much reminiscent
of the AMM decomposition formula for some model X into a pair of the BGW
models. At the same time, X, which still has to be found, is the pure gauge
limit of the elliptic Selberg integral. Presumably, it is again a BGW model,
only in the Dijkgraaf-Vafa double cut phase.Comment: 21 page
Optical Magnetometry
Some of the most sensitive methods of measuring magnetic fields utilize
interactions of resonant light with atomic vapor. Recent developments in this
vibrant field are improving magnetometers in many traditional areas such as
measurement of geomagnetic anomalies and magnetic fields in space, and are
opening the door to new ones, including, dynamical measurements of bio-magnetic
fields, detection of nuclear magnetic resonance (NMR), magnetic-resonance
imaging (MRI), inertial-rotation sensing, magnetic microscopy with cold atoms,
and tests of fundamental symmetries of Nature.Comment: 11 pages; 4 figures; submitted to Nature Physic
Amyloid-Mediated Sequestration of Essential Proteins Contributes to Mutant Huntingtin Toxicity in Yeast
BACKGROUND: Polyglutamine expansion is responsible for several neurodegenerative disorders, among which Huntington disease is the most well-known. Studies in the yeast model demonstrated that both aggregation and toxicity of a huntingtin (htt) protein with an expanded polyglutamine region strictly depend on the presence of the prion form of Rnq1 protein ([PIN+]), which has a glutamine/asparagine-rich domain. PRINCIPAL FINDINGS: Here, we showed that aggregation and toxicity of mutant htt depended on [PIN+] only quantitatively: the presence of [PIN+] elevated the toxicity and the levels of htt detergent-insoluble polymers. In cells lacking [PIN+], toxicity of mutant htt was due to the polymerization and inactivation of the essential glutamine/asparagine-rich Sup35 protein and related inactivation of another essential protein, Sup45, most probably via its sequestration into Sup35 aggregates. However, inhibition of growth of [PIN+] cells depended on Sup35/Sup45 depletion only partially, suggesting that there are other sources of mutant htt toxicity in yeast. CONCLUSIONS: The obtained data suggest that induced polymerization of essential glutamine/asparagine-rich proteins and related sequestration of other proteins which interact with these polymers represent an essential source of htt toxicity
Parent formulation at the Lagrangian level
The recently proposed first-order parent formalism at the level of equations
of motion is specialized to the case of Lagrangian systems. It is shown that
for diffeomorphism-invariant theories the parent formulation takes the form of
an AKSZ-type sigma model. The proposed formulation can be also seen as a
Lagrangian version of the BV-BRST extension of the Vasiliev unfolded approach.
We also discuss its possible interpretation as a multidimensional
generalization of the Hamiltonian BFV--BRST formalism. The general construction
is illustrated by examples of (parametrized) mechanics, relativistic particle,
Yang--Mills theory, and gravity.Comment: 26 pages, discussion of the truncation extended, typos corrected,
references adde
First order parent formulation for generic gauge field theories
We show how a generic gauge field theory described by a BRST differential can
systematically be reformulated as a first order parent system whose spacetime
part is determined by the de Rham differential. In the spirit of Vasiliev's
unfolded approach, this is done by extending the original space of fields so as
to include their derivatives as new independent fields together with associated
form fields. Through the inclusion of the antifield dependent part of the BRST
differential, the parent formulation can be used both for on and off-shell
formulations. For diffeomorphism invariant models, the parent formulation can
be reformulated as an AKSZ-type sigma model. Several examples, such as the
relativistic particle, parametrized theories, Yang-Mills theory, general
relativity and the two dimensional sigma model are worked out in details.Comment: 36 pages, additional sections and minor correction
Exome-wide somatic mutation characterization of small bowel adenocarcinoma
Small bowel adenocarcinoma (SBA) is an aggressive disease with limited treatment options. Despite previous studies, its molecular genetic background has remained somewhat elusive. To comprehensively characterize the mutational landscape of this tumor type, and to identify possible targets of treatment, we conducted the first large exome sequencing study on a population-based set of SBA samples from all three small bowel segments. Archival tissue from 106 primary tumors with appropriate clinical information were available for exome sequencing from a patient series consisting of a majority of confirmed SBA cases diagnosed in Finland between the years 2003-2011. Paired-end exome sequencing was performed using Illumina HiSeq 4000, and OncodriveFML was used to identify driver genes from the exome data. We also defined frequently affected cancer signalling pathways and performed the first extensive allelic imbalance (Al) analysis in SBA. Exome data analysis revealed significantly mutated genes previously linked to SBA (TP53, KRAS, APC, SMAD4, and BRAF), recently reported potential driver genes (SOX9, ATM, and ARID2), as well as novel candidate driver genes, such as ACVR2A, ACVR1B, BRCA2, and SMARCA4. We also identified clear mutation hotspot patterns in ERBB2 and BRAF. No BRAF V600E mutations were observed. Additionally, we present a comprehensive mutation signature analysis of SBA, highlighting established signatures 1A, 6, and 17, as well as U2 which is a previously unvalidated signature. Finally, comparison of the three small bowel segments revealed differences in tumor characteristics. This comprehensive work unveils the mutational landscape and most frequently affected genes and pathways in SBA, providing potential therapeutic targets, and novel and more thorough insights into the genetic background of this tumor type.Peer reviewe
Ultrasound-Enhanced Drug Transport and Distribution in the Brain
Drug delivery in the brain is limited by slow drug diffusion in the brain tissue. This study tested the hypothesis that ultrasound can safely enhance the permeation of drugs in the brain. In vitro exposure to ultrasound at various frequencies (85 kHz, 174 kHz, and 1 MHz) enhanced the permeation of tritium-labeled molecules with molecular weight up to 70 kDa across porcine brain tissue. A maximum enhancement of 24-fold was observed at 85 kHz and 1,200 J/cm2. In vivo exposure to 1-MHz ultrasound further demonstrated the ability of ultrasound to facilitate molecule distribution in the brain of a non-human primate. Finally, ultrasound under conditions similar to those used in vivo was shown to cause no damage to plasmid DNA, siRNA, adeno-associated virus, and fetal rat cortical neurons over a range of conditions. Altogether, these studies demonstrate that ultrasound can increase drug permeation in the brain in vitro and in vivo under conditions that did not cause detectable damage
Differential clonal evolution in oesophageal cancers in response to neo-adjuvant chemotherapy
How chemotherapy affects carcinoma genomes is largely unknown. Here we report whole-exome and deep sequencing of 30 paired oesophageal adenocarcinomas sampled before and after neo-adjuvant chemotherapy. Most, but not all, good responders pass through genetic bottlenecks, a feature associated with higher mutation burden pre-treatment. Some poor responders pass through bottlenecks, but re-grow by the time of surgical resection, suggesting a missed therapeutic opportunity. Cancers often show major changes in driver mutation presence or frequency after treatment, owing to outgrowth persistence or loss of sub-clones, copy number changes, polyclonality and/or spatial genetic heterogeneity. Post-therapy mutation spectrum shifts are also common, particularly C>A and TT>CT changes in good responders or bottleneckers. Post-treatment samples may also acquire mutations in known cancer driver genes (for example, SF3B1, TAF1 and CCND2) that are absent from the paired pre-treatment sample. Neo-adjuvant chemotherapy can rapidly and profoundly affect the oesophageal adenocarcinoma genome. Monitoring molecular changes during treatment may be clinically useful
Targeting immune checkpoints potentiates immunoediting and changes the dynamics of tumor evolution
The cancer immunoediting hypothesis assumes the immune system sculpts the cancer genome. Here the authors show, in a mouse model, that neutral evolution outweighs the effects of immunoselection and that immune checkpoint blockade potentiates the immunoediting, switching the system to non-neutral evolution
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