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 MgB2_{2} 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 $\pi$ and $\sigma$ bands, which depend on the disorder in different way; namely, as the disorder increases, it reduces more effectively the relaxation times of $\pi$ than of $\sigma$ bands, as suggested by a recent calculation [1].Comment: 12 pages, 5 figure

RVB Contribution to Superconductivity in MgB2MgB_2

We view $MgB_2$ as electronically equivalent to (non-staggered) graphite ($B^-$ layer) that has undergone a zero gap semiconductor to a superconductor phase transition by a large c-axis (chemical) pressure due to $Mg^{++}$ 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 $B^-$ (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 $d=3$.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