Multiple quantum solid-state NMR indicates a parallel, not antiparallel, organization of β-sheets in Alzheimer's β-amyloid fibrils

Senile plaques associated with Alzheimer's disease contain deposits of fibrils formed by 39- to 43-residue β-amyloid peptides with possible neurotoxic effects. X-ray diffraction measurements on oriented fibril bundles have indicated an extended β-sheet structure for Alzheimer's β-amyloid fibrils and other amyloid fibrils, but the supramolecular organization of the β-sheets and other structural details are not well established because of the intrinsically noncrystalline, insoluble nature of amyloid fibrils. Here we report solid-state NMR measurements, using a multiple quantum (MQ) 13C NMR technique, that probe the β-sheet organization in fibrils formed by the full-length, 40-residue β-amyloid peptide (Aβ1–40). Although an antiparallel β-sheet organization often is assumed and is invoked in recent structural models for full-length β-amyloid fibrils, the MQNMR data indicate an in-register, parallel organization. This work provides site-specific, atomic-level structural constraints on full-length β-amyloid fibrils and applies MQNMR to a significant problem in structural biology.

Diversity Arrays: a solid state technology for sequence information independent genotyping

Here we present the successful application of the microarray technology platform to the analysis of DNA polymorphisms. Using the rice genome as a model, we demonstrate the potential of a high-throughput genome analysis method called Diversity Array Technology, DArT‘. In the format presented here the technology is assaying for the presence (or amount) of a specific DNA fragment in a representation derived from the total genomic DNA of an organism or a population of organisms. Two different approaches are presented: the first involves contrasting two representations on a single array while the second involves contrasting a representation with a reference DNA fragment common to all elements of the array. The Diversity Panels created using this method allow genetic fingerprinting of any organism or group of organisms belonging to the gene pool from which the panel was developed. Diversity Arrays enable rapid and economical application of a highly parallel, solid-state genotyping technology to any genome or complex genomic mixtures.

Effect of lactose solid-state on the aerosolization performance of drug-carrier mixtures

Lactose, in particular α-lactose monohydrate, is the most used carrier for inhalation. Its surface and solid-state properties are of paramount importance in determining drug aerosolization performance. However, these properties may be altered by processing, such as micronization, thus affecting the product performance and stability. The present research project focused on the study of the effect of lactose solid-state on the aerosolization performance of drug-carrier mixtures, giving particular attention to the impact of micronization on lactose physico-chemical properties. The formation of a fraction of hygroscopic anhydrous α-lactose, rather than amorphous lactose, as a consequence of the mechanical stress stemming from micronization was evidenced by 1H NMR, XRPD and DSC analyses performed on samples of micronized lactose. The development of a new DVS method capable to identify and quantify different forms of α-lactose (hygroscopic anhydrous, stable anhydrous and amorphous), even simultaneously present in the same sample, confirmed the results obtained with the above-mentioned techniques. The influence of lactose solid-state on drug respirability was then evaluated through the preparation and in vitro aerodynamic assessment of ternary and binary mixtures containing two different drugs. In particular, the use, as carriers, of anhydrous forms of α-lactose in place of the conventional α-lactose monohydrate resulted in significantly improved respirability in the case of salbutamol sulphate and poorer performance in the case of budesonide. In an attempt to rationalize the obtained results, IGC was selected as a tool to investigate possible variations in the surface energy of the studied lactose carriers and APIs. A direct correlation between the total surface free energy of lactose carriers and drug respirability was not found. However, salbutamol sulphate and budesonide exhibited different specific surface free energy, to which the difference in the aerosolization performance may be, at least in part, ascribed.

Pilot study of hyperopic LASIK using the solid-state laser technology

Background To evaluate and report the visual, refractive, and aberrometric outcomes of LASIK for the correction of low to moderate hyperopia in a pilot group using a commercially available solid-state laser. Methods Prospective pilot study including 11 consecutive eyes with low to moderate hyperopia of six patients undergoing LASIK surgery using the Pulzar Z1 solid-state laser (CustomVis Laser Pty Ltd., currently CV Laser). Visual, refractive, and aberrometric changes were evaluated. Potential complications were evaluated as well. Mean follow-up time was 6.6 months (range, 3 to 11 months). Results A significant improvement in LogMAR uncorrected distance visual acuity (UDVA) was observed postoperatively (p = 0.01). No significant change was detected in LogMAR corrected distance visual acuity (CDVA) (p = 0.21). Postoperative LogMAR UDVA was 0.1 (about 20/25) or better in ten eyes (90.9 %). Mean overall efficacy and safety indices were 1.03 and 1.12. Postoperatively, no losses of lines of CDVA were observed. Postoperative spherical equivalent was within ±1.00 D in ten eyes (90.9 %). With regard to aberrations, no statistically significant changes were found in higher order and primary coma RMS postoperatively (p ≥ 0.21), and only minimal but statistically significant negativization of primary spherical aberration (p = 0.02) was observed. No severe complications were observed. Conclusion LASIK surgery using the solid-state laser technology seems to be a useful procedure for the correction of low to moderate hyperopia, with minimal induction of higher order aberrations.

Influence of the Difference Between Corneal and Refractive Astigmatism on LASIK Outcomes Using Solid-State Technology

Purpose: To evaluate the influence of the difference between preoperative corneal and refractive astigmatism [ocular residual astigmatism (ORA)] on outcomes obtained after laser in situ keratomileusis (LASIK) surgery for correction of myopic astigmatism using the solid-state laser technology. Methods: One hundred one consecutive eyes with myopia or myopic astigmatism of 55 patients undergoing LASIK surgery using the Pulzar Z1 solid-state laser (CustomVis Laser Pty Ltd, currently CV Laser) were included. Visual and refractive changes at 6 months postoperatively and changes in ORA and anterior corneal astigmatism and posterior corneal astigmatism (PCA) were analyzed. Results: Postoperatively, uncorrected distance visual acuity improved significantly (P < 0.01). Likewise, refractive cylinder magnitude and spherical equivalent were reduced significantly (P < 0.01). In contrast, no significant changes were observed in ORA magnitude (P = 0.81) and anterior corneal astigmatism (P = 0.12). The mean overall efficacy and safety indices were 0.96 and 1.01, respectively. These indices were not correlated with preoperative ORA (r = −0.15, P = 0.15). Furthermore, a significant correlation was found between ORA (r = 0.81, P < 0.01) and PCA postoperatively, but not preoperatively (r = 0.12, P = 0.25). Likewise, a significant correlation of ORA with manifest refraction was only found postoperatively (r = −0.38, P < 0.01). Conclusions: The magnitude of ORA does not seem to be a predictive factor of efficacy and safety of myopic LASIK using a solid-state laser platform. The higher relevance of PCA after surgery in some cases may explain the presence of unexpected astigmatic residual refractive errors.

Summaries of physical research in research in metallurgy, solid state physics and ceramics.

"January 1957 (TISE Issuance Date)."

Summaries of physical research in research in metallurgy, solid state physics and ceramics.

"July 1959 (TIS Issuance Date)."

Summaries of the UDAEC basic research programs in metallurgy, solid state physics and ceramics.

"January 1964 (DTIE Issuance Date)."

Summaries of the UDAEC basic research programs in metallurgy, solid state physics and ceramics : (fiscal year 1964)

"January 1965 (DTIE Issuance Date)."

Solid state data acquisition and processing system (SSDAPS). Volume III: description, installation, calibration, and operating procedures. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Summaries of the UDAEC basic research programs in metallurgy, solid state physics and ceramics.

"June 1961 (OIT Issuance Date)."

A solid state digital data recorder for monitoring autmotive crash environments. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Potential means of cost reduction in grade crossings motorist-warning control equipment. Volume II: comparison of solid state and relay devices and techniques. Final report.

Transportation Systems Center, Cambridge, Mass.

Solid state data acquisition and processing system (SSDAPS). Volume I: system summary and volume II: description, operation, and verification test report. Final report.

National Highway Traffic Safety Administration, Washington, D.C.