Optimizing aerosolization of a high-dose L-arginine powder for pulmonary delivery

In this study a carrier-free dry powder inhalation (DPI) containing L-arginine (ARG) was developed. As such, it is proposed that ARG could be used for adjunctive treatment of cystic fibrosis and/or tuberculosis. Various processing methods were used to manufacture high-dose formulation batches consisting various amounts of ARG and excipients. The formulations were evaluated using several analytical methods to assess suitability for further investigation. Several batches had enhanced in vitro aerolization properties. Significant future challenges include the highly hygroscopic nature of unformulated ARG powder and identifying the scale of dose of ARG required to achieve the response in lungs

Long-range coherence and mesoscopic transport in N-S metallic structures

We review the mesoscopic transport in a diffusive proximity superconductor made of a normal metal (N) in metallic contact with a superconductor (S). The Andreev reflection of electrons on the N-S interface is responsible for the diffusion of electron pairs in N. Superconducting-like properties are induced in the normal metal. In particular, the conductivity of the N metal is locally enhanced by the proximity effect. A re-entrance of the metallic conductance occurs when all the energies involved (e.g. temperature and voltage) are small. The relevant characteristic energy is the Thouless energy which is $\hbar$ divided by the diffusion time for an electron travelling throughout the sample. In loop-shaped devices, a 1/T temperature-dependent oscillation of the magnetoresistance arises with a large amplitude from the long-range coherence of low-energy pairs.Comment: Review paper, 13 pages with 5 included epsf figures, to appear in Superlattices and Microstructures, minor change

Andreev Tunneling in Strongly Interacting Quantum Dots

We review recent work on resonant Andreev tunneling through a strongly interacting quantum dot connected to a normal and to a superconducting lead. We derive a general expression for the current flowing in the structure and discuss the linear and non-linear transport in the nonperturbative regime. New effects associated to the Kondo resonance combined with the two-particle tunneling arise. The Kondo anomaly in the $I-V$ characteristics depends on the relative size of the gap energy and the Kondo temperature.Comment: 8 pages, 4 figures; submitted to Superlattices and Microstructure

In-vitro evaluation of the shear bond strength and fluoride release of a new bioactive dental composite material

The aim of this study was (1) to determine and compare the shear bond strength (SBS) of a bioactive composite ?Activa Bioactive Restorative? with and without bonding agent and a nanocomposite ?Filtek Z350 XT/ Z350? and (2) to measure and co

Andreev tunnelling in quantum dots: A slave-boson approach

We study a strongly interacting quantum dot connected to a normal and to a superconducting lead. By means of the slave-boson technique we investigate the low temperature regime and discuss electrical transport through the dot. We find that the zero bias anomaly in the current-voltage characteristics which is associated to the occurance of the Kondo resonance in the quantum dot, is enhanced in the presence of superconductivity, due to resonant Andreev scattering.Comment: 4 pages, 1 figur

Kondo-resonance, Coulomb blockade, and Andreev transport through a quantum dot

We study resonant tunneling through an interacting quantum dot coupled to normal metallic and superconducting leads. We show that large Coulomb interaction gives rise to novel effects in Andreev transport. Adopting an exact relation for the Green's function, we find that at zero temperature, the linear response conductance is enhanced due to Kondo-Andreev resonance in the Kondo limit, while it is suppressed in the empty site limit. In the Coulomb blockaded region, on the other hand, the conductance is reduced more than the corresponding conductance with normal leads because large charging energy suppresses Andreev reflection.Comment: 3 pages Revtex, 4 Postscript figures, accepted for publication in Phys. Rev.

Extraordinary Temperature Dependence of the Resonant Andreev Reflection

An extraordinary temperature dependence of the resonant Andreev reflection via discrete energy level in a normal-metal / quantum-dot / superconductor (N-QD-S) system is predicted theoretically by using Green function technique. The width of zero bias conductance peak in N-QD-S is about $\sqrt{\Gamma _L^2+\Gamma_R^2}$ and does not exhibit thermal broadening, where $\Gamma_L$ and $\Gamma_R$ are the coupling strength between QD and leads. Considering the intra-dot Coulomb interaction, the Coulomb blockade oscillations conducted by Andreev reflection differs dramatically from that in N-QD-N. Instead of thermal broadening, finite temperature induces more resonant peaks around the oscillation peaks of zero temperature. This effect can be applied to determine the coupling strength and QD level spacing in N-QD-S.Comment: 11 pages, 3 figures, LaTe

Neutralization mechanism of a highly potent antibody against Zika virus

The rapid spread of Zika virus (ZIKV), which causes microcephaly and Guillain-Barré syndrome, signals an urgency to identify therapeutics. Recent efforts to rescreen dengue virus human antibodies for ZIKV cross-neutralization activity showed antibody C10 as one of the most potent. To investigate the ability of the antibody to block fusion, we determined the cryoEM structures of the C10-ZIKV complex at pH levels mimicking the extracellular (pH8.0), early (pH6.5) and late endosomal (pH5.0) environments. The 4.0 Å resolution pH8.0 complex structure shows that the antibody binds to E proteins residues at the intra-dimer interface, and the virus quaternary structure-dependent inter-dimer and inter-raft interfaces. At pH6.5, antibody C10 locks all virus surface E proteins, and at pH5.0, it locks the E protein raft structure, suggesting that it prevents the structural rearrangement of the E proteins during the fusion event—a vital step for infection. This suggests antibody C10 could be a good therapeutic candidate

Associatioin of Plasma Aβ Peptides with Blood Pressure in the Elderly

Background Aß peptides are often considered as catabolic by-products of the amyloid ß protein precursor (APP), with unknown physiological functions. However, several biological properties have been tentatively attributed to these peptides, including a role in vasomotion. We assess whether plasma Aß peptide levels might be associated with systolic and diastolic blood pressure values (SBP and DBP, respectively). Methodology/Principal Findings Plasma Aß1-40 and Aß1-42 levels were measured using an xMAP-based assay in 1,972 individuals (none of whom were taking antihypertensive drugs) from 3 independent studies: the French population-based 3C and MONA-LISA (Lille) studies (n = 627 and n = 769, respectively) and the Australian, longitudinal AIBL study (n = 576). In the combined sample, the Aß1-42/ Aß1-40 ratio was significantly and inversely associated with SBP (p = 0.03) and a similar trend was observed for DBP (p = 0.06). Using the median age (69) as a cut-off, the Aß1-42/Aß1-40 ratio was strongly associated with both SBP and DBP in elderly individuals (p = 0.002 and p = 0.03, respectively). Consistently, a high Aß1-42/ Aß1-40 ratio was associated with a lower risk of hypertension in both the combined whole sample (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.56-0.90) and (to an even greater extent) in the elderly subjects (OR, 0.53; 95% CI, 0.37–0.75). Lastly, all these associations appeared to be primarily driven by the level of plasma Aß1-40. Conclusion The plasma Aß1-42/Aß1-40 ratio is inversely associated with SBP, DBP and the risk of hypertension in elderly subjects, suggesting that Aß peptides affect blood pressure in vivo. These results may be particularly relevant in Alzheimer\u27s disease, in which a high Aß1-42/Aß1-40 plasma ratio is reportedly associated with a decreased risk of incident disease

Self-Collected Mid-Turbinate Swabs for the Detection of Respiratory Viruses in Adults with Acute Respiratory Illnesses

BACKGROUND: The gold standard for respiratory virus testing is a nasopharyngeal (NP) swab, which is collected by a healthcare worker. Midturbinate (MT) swabs are an alternative due to their ease of collection and possible self-collection by patients. The objective of this study was to compare the respiratory virus isolation of flocked MT swabs compared to flocked NP swabs. METHODS: Beginning in October 2008, healthy adults aged 18 to 69 years were recruited into a cohort and followed up for symptoms of influenza. They were asked to have NP and MT swabs taken as soon as possible after the onset of a fever or two or more respiratory symptoms with an acute onset. The swabs were tested for viral respiratory infections using Seeplex® RV12 multiplex PCR detection kit. Seventy six pairs of simultaneous NP and MT swabs were collected from 38 symptomatic subjects. Twenty nine (38%) of these pairs were positive by either NP or MT swabs or both. Sixty nine (91%) of the pair results were concordant. Two samples (3%) for hCV OC43/HKU1 and 1 sample (1%) for rhinovirus A/B were positive by NP but negative by MT. One sample each for hCV 229E/NL63, hCV OC43/HKU1, respiratory syncytial virus A, and influenza B were positive by MT but negative by NP. CONCLUSIONS: Flocked MT swabs are sensitive for the diagnosis of multiple respiratory viruses. Given the ease of MT collection and similar results between the two swabs, it is likely that MT swabs should be the preferred method of respiratory cell collection for outpatient studies. In light of this data, larger studies should be performed to ensure that this still holds true and data should also be collected on the patient preference of collection methods