915 research outputs found
Two-channel point-contact tunneling theory of superconductors
We introduce a two-channel tunneling model to generalize the widely used BTK
theory of point-contact conductance between a normal metal contact and
superconductor. Tunneling of electrons can occur via localized surface states
or directly, resulting in a Fano resonance in the differential conductance
. We present an analysis of within the two-channel model when
applied to soft point-contacts between normal metallic silver particles and
prototypical heavy-fermion superconductors CeCoIn and CeRhIn at high
pressures. In the normal state the Fano line shape of the measured is well
described by a model with two tunneling channels and a large
temperature-independent background conductance. In the superconducting state a
strongly suppressed Andreev reflection signal is explained by the presence of
the background conductance. We report Andreev signal in CeCoIn consistent
with standard -wave pairing, assuming an equal mixture of
tunneling into [100] and [110] crystallographic interfaces. Whereas in
CeRhIn at 1.8 and 2.0 GPa the signal is described by a -wave
gap with reduced nodal region, i.e., increased slope of the gap opening on the
Fermi surface. A possibility is that the shape of the high-pressure Andreev
signal is affected by the proximity of a line of quantum critical points that
extends from 1.75 to 2.3 GPa, which is not accounted for in our description of
the heavy-fermion superconductor.Comment: 13 pages, 13 figure
Digested wheat gluten inhibits binding between leptin and its receptor
BACKGROUND: Leptin resistance is considered a primary risk factor for obesity. It has been hypothesized that dietary cereal grain protein could cause leptin resistance by preventing leptin from binding to its receptor. Non-degraded dietary wheat protein has been found in human serum at a mean level of 41 ng/mL. Here, we report our findings from testing whether enzymatically digested gluten from wheat prevents leptin from binding to the leptin receptor in vitro. Gluten from wheat was digested with pepsin and trypsin under physiological conditions. Pepsin and trypsin activity was removed from the gluten digest with a 10 kDa spin-filter or by heat treatment at 100°C for 30 min. Binding to the leptin receptor of leptin mixed with gluten digest at a series of concentrations was measured using surface plasmon resonance technology. RESULTS: Binding of the gluten digest to the leptin receptor was not detected. Spin-filtered gluten digest inhibited binding of leptin to the leptin receptor, with 50% inhibition at a gluten digest concentration of ~10 ng/mL. Heat-treated gluten digest did not inhibit leptin binding. CONCLUSIONS: Digested wheat gluten inhibits binding of leptin to the leptin receptor, with half-maximal inhibition at 10 ng/mL. The inhibition is significant at clinically relevant concentrations and could therefore serve as a novel pathway to investigate to understand the molecular basis of leptin resistance, obesity and associated disorders
Age at Seroconversion, HLA Genotype, and Specificity of Autoantibodies in Progression of Islet Autoimmunity in Childhood
Context: Children with initial autoantibodies to either insulin (IAA) or glutamic acid decarboxylase (GADA) differ in peak age of seroconversion and have different type 1 diabetes (T1D) risk gene associations, suggesting heterogeneity in the disease process. Objective: To compare the associations of age at seroconversion, HLA risk, and specificity of secondary autoantibodies with the progression of islet autoimmunity between children with either IAA or GADA as their first autoantibody. Design and methods: A cohort of 15,253 children with HLA-associated increased risk of T1D participated in a follow-up program in which islet autoantibodies were regularly measured. The median follow-up time was 6.7 years. Spearman correlation, Kaplan-Meier survival plots, and Cox proportional-hazard models were used for statistical analyses. Results: Persistent positivity for at least one of the tested autoantibodies was detected in 998 children; 388 of children progressed to clinical T1D. Young age at initial seroconversion was associated with a high probability of expansion of IAA-initiated autoimmunity and progression to clinical diabetes, whereas expansion of GADA-initiated autoimmunity and progression to diabetes were not dependent on initial seroconversion age. The strength of HLA risk affected the progression of both IAA- and GADA-initiated autoimmunity. The simultaneous appearance of two other autoantibodies increased the rate of progression to diabetes compared with that of a single secondary autoantibody among subjects with GADA-initiated autoimmunity but not among those with IAA as the first autoantibody. Conclusions: Findings emphasize the differences in the course of islet autoimmunity initiated by either IAA or GADA supporting heterogeneity in the pathogenic process.Peer reviewe
Needle biopsy through the abdominal wall for the diagnosis of gastrointestinal stromal tumour - Does it increase the risk for tumour cell seeding and recurrence?
Purpose: Preoperative percutaneous transabdominal wall biopsy may be considered to diagnose gastrointestinal stromal tumour (GIST) and plan preoperative treatment with tyrosine kinase inhibitors when an endoscopic biopsy is not possible. Hypothetically, a transabdominal wall biopsy might lead to cell seeding and conversion of a local GIST to a disseminated one. We investigated the influence of preoperative needle biopsy on survival outcomes. Methods: We collected the clinical data from hospital case records of the 397 patients who participated in the Scandinavian Sarcoma Group (SSG) XVIII/Arbeitsgemeinschaft Internistische Onkologie (AIO) randomised trial and who had a transabdominal fine needle and/or core needle biopsy carried out prior to study entry. The SSG XVIII/AIO trial compared 1 and 3 years of adjuvant imatinib in a patient population with a high risk of GIST recurrence after macroscopically radical surgery. The primary end-point was recurrence-free survival (RFS), and the secondary end-points included overall survival (OS). Results: A total of 47 (12.0%) out of the 393 patients with data available underwent a percutaneous biopsy. No significant difference in RFS or OS was found between the patients who underwent or did not undergo a percutaneous biopsy either in the entire series or in subpopulation analyses, except for a statistically significant RFS advantage for patients who had a percutaneous biopsy and a tumour >= 10 cm in diameter. Conclusion: A preoperative diagnostic percutaneous biopsy of a suspected GIST may not increase the risk for GIST recurrence in a patient population who receive adjuvant imatinib after the biopsy. (C) 2016 Elsevier Ltd. All rights reserved.Peer reviewe
The Scandinavian Sarcoma Group Central Register : 6,000 patients after 25 years of monitoring of referral and treatment of extremity and trunk wall soft-tissue sarcoma
Purpose - We wanted to examine the potential of the Scandinavian Sarcoma Group (SSG) Central Register, and evaluate referral and treatment practice for soft-tissue sarcomas in the extremities and trunk wall (STS) in the Nordic countries. Background - Based on incidence rates from the literature, 8,150 (7,000-9,300) cases of STS of the extremity and trunk wall should have been diagnosed in Norway, Finland, Iceland, and Sweden from 1987 through 2011. The SSG Register has 6,027 cases registered from this period, with 5,837 having complete registration of key variables. 10 centers have been reporting to the Register. The 5 centers that consistently report treat approximately 90% of the cases in their respective regions. The remaining centers have reported all the patients who were treated during certain time periods, but not for the entire 25-year period. Results - 59% of patients were referred to a sarcoma center untouched, i.e. before any attempt at open biopsy. There was an improvement from 52% during the first 5 years to 70% during the last 5 years. 50% had wide or better margins at surgery. Wide margins are now achieved less often than 20 years ago, in parallel with an increase in the use of radiotherapy. For the centers that consistently report, 97% of surviving patients are followed for more than 4 years. Metastasis-free survival (MFS) increased from 67% to 73% during the 25-year period. Interpretation - The Register is considered to be representative of extremity and trunk wall sarcoma disease in the population of Scandinavia, treated at the reporting centers. There were no clinically significant differences in treatment results at these centers.Peer reviewe
Assigning roles to DNA regulatory motifs using comparative genomics
Motivation: Transcription factors (TFs) are crucial during the lifetime of the cell. Their functional roles are defined by the genes they regulate. Uncovering these roles not only sheds light on the TF at hand but puts it into the context of the complete regulatory network
Observational and Dynamical Characterization of Main-Belt Comet P/2010 R2 (La Sagra)
We present observations of comet-like main-belt object P/2010 R2 (La Sagra)
obtained by Pan-STARRS 1 and the Faulkes Telescope-North on Haleakala in
Hawaii, the University of Hawaii 2.2 m, Gemini-North, and Keck I telescopes on
Mauna Kea, the Danish 1.54 m telescope at La Silla, and the Isaac Newton
Telescope on La Palma. An antisolar dust tail is observed from August 2010
through February 2011, while a dust trail aligned with the object's orbit plane
is also observed from December 2010 through August 2011. Assuming typical phase
darkening behavior, P/La Sagra is seen to increase in brightness by >1 mag
between August 2010 and December 2010, suggesting that dust production is
ongoing over this period. These results strongly suggest that the observed
activity is cometary in nature (i.e., driven by the sublimation of volatile
material), and that P/La Sagra is therefore the most recent main-belt comet to
be discovered. We find an approximate absolute magnitude for the nucleus of
H_R=17.9+/-0.2 mag, corresponding to a nucleus radius of ~0.7 km, assuming an
albedo of p=0.05. Using optical spectroscopy, we find no evidence of
sublimation products (i.e., gas emission), finding an upper limit CN production
rate of Q_CN<6x10^23 mol/s, from which we infer an H2O production rate of
Q_H2O<10^26 mol/s. Numerical simulations indicate that P/La Sagra is
dynamically stable for >100 Myr, suggesting that it is likely native to its
current location and that its composition is likely representative of other
objects in the same region of the main belt, though the relatively close
proximity of the 13:6 mean-motion resonance with Jupiter and the (3,-2,-1)
three-body mean-motion resonance with Jupiter and Saturn mean that dynamical
instability on larger timescales cannot be ruled out.Comment: 23 pages, 13 figures, accepted for publication in A
Risk Factors for Gastrointestinal Stromal Tumor Recurrence in Patients Treated With Adjuvant Imatinib
Peer reviewe
Protein GB1 Folding and Assembly from Structural Elements
Folding of the Protein G B1 domain (PGB1) shifts with increasing salt concentration from a cooperative assembly of inherently unstructured subdomains to an assembly of partly pre-folded structures. The salt-dependence of pre-folding contributes to the stability minimum observed at physiological salt conditions. Our conclusions are based on a study in which the reconstitution of PGB1 from two fragments was studied as a function of salt concentrations and temperature using circular dichroism spectroscopy. Salt was found to induce an increase in β-hairpin structure for the C-terminal fragment (residues 41 – 56), whereas no major salt effect on structure was observed for the isolated N-terminal fragment (residues 1 – 41). In line with the increasing evidence on the interrelation between fragment complementation and stability of the corresponding intact protein, we also find that salt effects on reconstitution can be predicted from salt dependence of the stability of the intact protein. Our data show that our variant (which has the mutations T2Q, N8D, N37D and reconstitutes in a manner similar to the wild type) displays the lowest equilibrium association constant around physiological salt concentration, with higher affinity observed both at lower and higher salt concentration. This corroborates the salt effects on the stability towards denaturation of the intact protein, for which the stability at physiological salt is lower compared to both lower and higher salt concentrations. Hence we conclude that reconstitution reports on molecular factors that govern the native states of proteins
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