143 research outputs found
Antibody mimetic receptor proteins for label-free biosensors
The development of high sensitivity biosensors, for example for clinical diagnostics, requires the
identification of suitable receptor molecules which offer high stability, specificity and affinity, even when
embedded into solid-state biosensor transducers. Here, we present an electrochemical biosensor
employing small synthetic receptor proteins (Mw < 15 kDa) which emulate antibodies but with improved
stability, sensitivity and molecular recognition properties, in particular when immobilized on a solid
sensor surface. The synthetic receptor protein is a non-antibody-based protein scaffold with variable
peptide regions inserted to provide the specific binding, and was designed to bind anti-myc tag antibody
(Mw � 150 kDa), as a proof-of-principle exemplar. Both the scaffold and the selected receptor protein
were found to have high thermostability with melting temperatures of 101 �C and 85 �C, respectively.
Furthermore, the secondary structures of the receptor protein were found to be very similar to that of
the original native scaffold, despite the insertion of variable peptide loops that create the binding sites. A
label-free electrochemical sensor was fabricated by functionalising a microfabricated gold electrode
with the receptor protein. A change in the phase of the electrochemical impedance was observed when
the biosensor was subjected to anti-myc tag antibodies at concentrations between 6.7 pM and 6.7 nM.
These findings demonstrate that these non-antibody receptor proteins are excellent candidates for
recognition molecules in label-free biosensors
Rational design of DNA nanostructures for single molecule biosensing
The ability to detect low concentrations of biomarkers in patient samples is one of the cornerstones of modern healthcare. In general, biosensing approaches are based on measuring signals resulting from the interaction of a large ensemble of molecules with the sensor. Here, we report a biosensor platform using DNA origami featuring a central cavity with a target-specific DNA aptamer coupled with a nanopore read-out to enable individual biomarker detection. We show that the modulation of the ion current through the nanopore upon the DNA origami translocation strongly depends on the presence of the biomarker in the cavity. We exploit this to generate a biosensing platform with a limit of detection of 3 nM and capable of the detection of human C-reactive protein (CRP) in clinically relevant fluids. Future development of this approach may enable multiplexed biomarker detection by using ribbons of DNA origami with integrated barcoding
Distinct Clinical and Laboratory Patterns of Pneumocystis jirovecii Pneumonia in Renal Transplant Recipients.
Late post-transplant Pneumocystis jirovecii pneumonia (PcP) has been reported in many renal transplant recipients (RTRs) centers using universal prophylaxis. Specific features of PcP compared to other respiratory infections in the same population are not well reported. We analyzed clinical, laboratory, administrative and radiological data of all confirmed PcP cases between January 2009 and December 2014. To identify factors specifically associated with PcP, we compared clinical and laboratory data of RTRs with non-PcP. Over the study period, 36 cases of PcP were identified. Respiratory distress was more frequent in PcP compared to non-PcP (tachypnea: 59%, 20/34 vs. 25%, 13/53, p = 0.0014; dyspnea: 70%, 23/33 vs. 44%, 24/55, p = 0.0181). In contrast, fever was less frequent in PcP compared to non-PcP pneumonia (35%, 11/31 vs. 76%, 42/55, p = 0.0002). In both cohorts, total lymphocyte count and serum sodium decreased, whereas lactate dehydrogenase (LDH) increased at diagnosis. Serum calcium increased in PcP and decreased in non-PcP. In most PcP cases (58%, 21/36), no formal indication for restart of PcP prophylaxis could be identified. Potential transmission encounters, suggestive of interhuman transmission, were found in 14/36, 39% of patients. Interhuman transmission seems to contribute importantly to PcP among RTRs. Hypercalcemia, but not elevated LDH, was associated with PcP when compared to non-PcP
Thermal conductivity of MgB in the superconducting state
We present thermal conductivity measurements on very pure and dense bulk
samples, as indicated by residual resistivity values as low as 0.5 mW cm and
thermal conductivity values higher than 200 W/mK. In the normal state we found
that the Wiedemann Franz law, in its generalized form, works well suggesting
that phonons do not contribute to the heat transport. The thermal conductivity
in the superconducting state has been analysed by using a two-gap model. Thank
to the large gap anisotropy we were able to evaluate quantitatively intraband
scattering relaxation times of and bands, which depend on the
disorder in different way; namely, as the disorder increases, it reduces more
effectively the relaxation times of than of bands, as
suggested by a recent calculation [1].Comment: 12 pages, 5 figure
RVB Contribution to Superconductivity in
We view as electronically equivalent to (non-staggered) graphite
( layer) that has undergone a zero gap semiconductor to a superconductor
phase transition by a large c-axis (chemical) pressure due to layers.
Further, like the \ppi bonded planar organic molecules, graphite is an old
resonating valence bond (RVB) system. The RVB's are the `preexisting cooper
pairs' in the `parental' zero gap semiconducting (graphite) sheets that
manifests themselves as a superconducting ground state of the transformed
metal. Some consequences are pointed out.Comment: 4 pages, 2 figure, RevTex. Based on a talk given at the Institute
Seminar Week, IMSc, Madras (12-16, Feb. 2001
Muon-spin-relaxation study of the magnetic penetration depth in MgB2
The magnetic vortex lattice (VL) of polycrystalline MgB2 has been
investigated by transverse-field muon-spin-relaxation (TF-MuSR). The evolution
of TF-MuSR depolarization rate, sigma, that is proportional to the second
moment of the field distribution of the VL has been studied as a function of
temperature and applied magnetic field. The low temperature value s exhibits a
pronounced peak near Hext = 75 mT. This behavior is characteristic of strong
pinning induced distortions of the VL which put into question the
interpretation of the low-field TF-MuSR data in terms of the magnetic
penetration depth lambda(T). An approximately constant value of sigma, such as
expected for an ideal VL in the London-limit, is observed at higher fields of
Hext > 0.4 T. The TF-MuSR data at Hext = 0.6 T are analyzed in terms of a
two-gap model. We obtain values for the gap size of D1 = 6.0 meV (2D1/kBTc =
3.6), D2 = 2.6 meV (2D2/kBTc = 1.6), a comparable spectral weight of the two
bands and a zero temperature value for the magnetic penetration depth of lambda
= 100 nm. In addition, we performed MuSR-measurements in zero external field
(ZF-MuSR). We obtain evidence that the muon site (at low temperature) is
located on a ring surrounding the center of the boron hexagon. Muon diffusion
sets in already at rather low temperature of T > 10 K. The nuclear magnetic
moments can account for the observed relaxation rate and no evidence for
electronic magnetic moments has been obtained.Comment: 15 pages, 4 figure
Epidemiology and outcomes of medically attended and microbiologically confirmed bacterial foodborne infections in solid organ transplant recipients
Food-safety measures are recommended to solid organ transplant (SOT) recipients. However, the burden of foodborne infections in SOT recipients has not been established. We describe the epidemiology and outcomes of bacterial foodborne infections in a nationwide cohort including 4405 SOT recipients in Switzerland between 2008 and 2018. Participants were prospectively followed for a median of 4.2 years with systematic collection of data on infections, and patient and graft-related outcomes. We identified 151 episodes of microbiologically confirmed bacterial foodborne infections occurring in median 1.6 years (IQR 0.58-3.40) after transplantation (131 [88%] Campylobacter spp. and 15 [10%] non-typhoidal Salmonella). The cumulative incidence of bacterial foodborne infections was 4% (95% CI 3.4-4.8). Standardized incidence rates were 7.4 (95% CI 6.2-8.7) and 4.6 (95% CI 2.6-7.5) for Campylobacter and Salmonella infections, respectively. Invasive infection was more common with Salmonella (33.3% [5/15]) compared to Campylobacter (3.2% [4/125]; p = .001). Hospital and ICU admission rates were 47.7% (69/145) and 4.1% (6/145), respectively. A composite endpoint of acute rejection, graft loss, or death occurred within 30 days in 3.3% (5/151) of cases. In conclusion, in our cohort bacterial foodborne infections were late post-transplant infections and were associated with significant morbidity, supporting the need for implementation of food-safety recommendations
Specific heat of classical disordered elastic systems
We study the thermodynamics of disordered elastic systems, applied to vortex
lattices in the Bragg glass phase. Using the replica variational method we
compute the specific heat of pinned vortons in the classical limit. We find
that the contribution of disorder is positive, linear at low temperature, and
exhibits a maximum. It is found to be important compared to other
contributions, e.g. core electrons, mean field and non linear elasticity that
we evaluate. The contribution of droplets is subdominant at weak disorder in
.Comment: 4 pages, RevTe
Physical Property Characterization of Bulk MgB2 Superconductor
We report synthesis, structure/micro-structure, resistivity under magnetic
field [R(T)H], Raman spectra, thermoelectric power S(T), thermal conductivity
K(T), and magnetization of ambient pressure argon annealed polycrystalline bulk
samples of MgB2, processed under identical conditions. The compound
crystallizes in hexagonal structure with space group P6/mmm. Transmission
electron microscopy (TEM) reveals electron micrographs showing various types of
defect features along with the presence of 3-4nm thick amorphous layers forming
the grain boundaries of otherwise crystalline MgB2. Raman spectra of the
compound at room temperature exhibited characteristic phonon peak at 600 cm-1.
Superconductivity is observed at 37.2K by magnetic susceptibility C(T),
resistivity R(T), thermoelectric power S(T), and thermal conductivity K(T)
measurements. The power law fitting of R(T) give rise to Debye temperature at
1400K which is found consistent with the theoretical fitting of S(T),
exhibiting ThetaD of 1410K and carrier density of 3.81x 1028/m3. Thermal
conductivity K(T) shows a jump at 38K, i.e., at Tc, which was missing in some
earlier reports. Critical current density (Jc) of up to 105 A/cm2 in 1-2T
(Tesla) fields at temperatures (T) of up to 10K is seen from magnetization
measurements. The irreversibility field, defined as the field related to
merging of M(H) loops is found to be 78, 68 and 42 kOe at 4, 10 and 20K
respectively. The superconducting performance parameters viz. irreversibility
field (Hirr) and critical current density Jc(H) of the studied MgB2 are
improved profoundly with addition of nano-SiC and nano-Diamond. The physical
property parameters measured for polycrystalline MgB2 are compared with earlier
reports and a consolidated insight of various physical properties is presented.Comment: 41 pages TEXT+Fig
Immunogenicity of High-Dose vs. MF59-adjuvanted vs. Standard Influenza Vaccine in Solid Organ Transplant Recipients: The STOP-FLU trial.
BACKGROUND
The immunogenicity of the standard influenza vaccine is reduced in solid-organ transplant (SOT) recipients, so that new vaccination strategies are needed in this population.
METHODS
Adult SOT recipients from nine transplant clinics in Switzerland and Spain were enrolled if they were >3 months after transplantation. High, with stratification by organ and time from transplant. The primary outcome was vaccine response rate, defined as a ≥4-fold increase of hemagglutination-inhibition titers to at least one vaccine strain at 28 days post-vaccination. Secondary outcomes included PCR-confirmed influenza and vaccine reactogenicity.
RESULTS
619 patients were randomized, 616 received the assigned vaccines, and 598 had serum available for analysis of the primary endpoint (standard, n=198; MF59-adjuvanted, n=205; high-dose, n=195 patients). Vaccine response rates were 42% (84/198) in the standard vaccine group, 60% (122/205) in the MF59-adjuvanted vaccine group, and 66% (129/195) in the high-dose vaccine group (difference in intervention vaccines vs. standard vaccine, 0.20 [97.5% CI 0.12-1]; p<0.001; difference in high-dose vs. standard vaccine, 0.24 [95% CI 0.16-1]; p<0.001; difference in MF59-adjuvanted vs. standard vaccine, 0.17 [97.5% CI 0.08-1]; p<0.001). Influenza occurred in 6% the standard, 5% in the MF59-adjuvanted, and 7% in the high-dose vaccine groups. Vaccine-related adverse events occurred more frequently in the intervention vaccine groups, but most of the events were mild.
CONCLUSIONS
In SOT recipients, use of an MF59-adjuvanted or a high-dose influenza vaccine was safe and resulted in a higher vaccine response rate.
TRIAL REGISTRATION
Clinicaltrials.gov NCT03699839
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