Ion-implantation induced anomalous surface amorphization in silicon

Spectroscopic ellipsometry (SE), high-depth-resolution Rutherford backscattering (RBS) and channeling have been used to examine the surface damage formed by room temperature N and B implantation into silicon. For the analysis of the SE data we used the conventional method of assuming appropriate optical models and fitting the model parameters (layer thicknesses and volume fraction of the amorphous silicon component in the layers) by linear regression. The dependence of the thickness of the surface-damaged silicon layer (beneath the native oxide layer) on the implantation parameters was determined: the higher the dose, the thicker the disordered layer at the surface. The mechanism of the surface amorphization process is explained in relation to the ion beam induced layer-by-layer amorphization. The results demonstrate the applicability of Spectroscopic ellipsometry with a proper optical model. RBS, as an independent cross-checking method supported the constructed optical model

Inhomogeneous Distribution of Components in Solid Protein Pharmaceuticals:Origins, Consequences, Analysis, and Resolutions

Successful development of stable solid protein formulations usually requires the addition of one or several excipients to achieve optimal stability. In these products, there is a potential risk of an inhomogeneous distribution of the various ingredients, specifically the ratio of protein and stabilizer may vary. Such inhomogeneity can be detrimental for stability but is mostly neglected in literature. In the past, it was challenging to analyze inhomogeneous component distribution, but recent advances in analytical techniques have revealed new options to investigate this phenomenon. This paper aims to review fundamental aspects of the inhomogeneous distribution of components of freeze-dried and spray-dried protein formulations. Four key topics will be presented and discussed, including the sources of component inhomogeneity, its consequences on protein stability, the analytical methods to reveal component inhomogeneity, and possible solutions to prevent or mitigate inhomogeneity

Sublinear time algorithms for earth mover's distance

We study the problem of estimating the Earth Mover’s Distance (EMD) between probability distributions when given access only to samples of the distributions. We give closeness testers and additive-error estimators over domains in [0, 1][superscript d], with sample complexities independent of domain size – permitting the testability even of continuous distributions over infinite domains. Instead, our algorithms depend on other parameters, such as the diameter of the domain space, which may be significantly smaller. We also prove lower bounds showing the dependencies on these parameters to be essentially optimal. Additionally, we consider whether natural classes of distributions exist for which there are algorithms with better dependence on the dimension, and show that for highly clusterable data, this is indeed the case. Lastly, we consider a variant of the EMD, defined over tree metrics instead of the usual l 1 metric, and give tight upper and lower bounds

Surface Engineering Methods for Powder Bed Printed Tablets to Optimize External Smoothness and Facilitate the Application of Different Coatings

In a previous attempt to achieve ileo-colonic targeting of bovine intestinal alkaline phosphatase (BIAP), we applied a pH-dependent coating, the ColoPulse coating, directly on powder bed printed (PBP) tablets. However, the high surface roughness necessitated an additional sub-coating layer [Nguyen, K. T. T., Pharmaceutics 2022]. In this study, we aimed to find a production method for PBP tablets containing BIAP that allows the direct application of coating systems. Alterations of the printing parameters, binder content, and printing layer height, when combined, were demonstrated to create visually less rough PBP tablets. The addition of ethanol vapor treatment further improved the surface’s smoothness significantly. These changes enabled the direct application of the ColoPulse, or enteric coating, without a sub-coating. In vitro release testing showed the desired ileo-colonic release or upper-intestinal release for ColoPulse or enteric-coated tablets, respectively. Tablets containing BIAP, encapsulated within an inulin glass, maintained a high enzymatic activity (over 95%) even after 2 months of storage at 2–8 °C. Importantly, the coating process did not affect the activity of BIAP. In this study, we demonstrate, for the first time, the successful production of PBP tablets with surfaces that are directly coatable with the ColoPulse coating while preserving the stability of the encapsulated biopharmaceutical, BIAP.</p

Host Transcription Profile in Nasal Epithelium and Whole Blood of Hospitalized Children Under 2 Years of Age With Respiratory Syncytial Virus Infection.

BACKGROUND: Most insights into the cascade of immune events after acute respiratory syncytial virus (RSV) infection have been obtained from animal experiments or in vitro models. METHODS: In this study, we investigated host gene expression profiles in nasopharyngeal (NP) swabs and whole blood samples during natural RSV and rhinovirus (hRV) infection (acute versus early recovery phase) in 83 hospitalized patients <2 years old with lower respiratory tract infections. RESULTS: Respiratory syncytial virus infection induced strong and persistent innate immune responses including interferon signaling and pathways related to chemokine/cytokine signaling in both compartments. Interferon-α/β, NOTCH1 signaling pathways and potential biomarkers HIST1H4E, IL7R, ISG15 in NP samples, or BCL6, HIST2H2AC, CCNA1 in blood are leading pathways and hub genes that were associated with both RSV load and severity. The observed RSV-induced gene expression patterns did not differ significantly in NP swab and blood specimens. In contrast, hRV infection did not as strongly induce expression of innate immunity pathways, and significant differences were observed between NP swab and blood specimens. CONCLUSIONS: We conclude that RSV induced strong and persistent innate immune responses and that RSV severity may be related to development of T follicular helper cells and antiviral inflammatory sequelae derived from high activation of BCL6

Determination of the primary structure and carboxyl pKAs of heparin-derived oligosaccharides by band-selective homonuclear-decoupled two-dimensional 1H NMR

Determination of the structure of heparin-derived oligosaccharides by 1H NMR is challenging because resonances for all but the anomeric protons cover less than 2 ppm. By taking advantage of increased dispersion of resonances for the anomeric H1 protons at low pD and the superior resolution of band-selective, homonuclear-decoupled (BASHD) two-dimensional 1H NMR, the primary structure of the heparin-derived octasaccharide ∆UA(2S)-[(1 → 4)-GlcNS(6S)-(1 → 4)-IdoA(2S)-]3-(1 → 4)-GlcNS(6S) has been determined, where ∆UA(2S) is 2-O-sulfated ∆4,5-unsaturated uronic acid, GlcNS(6S) is 6-O-sulfated, N-sulfated β-d-glucosamine and IdoA(2S) is 2-O-sulfated α-l-iduronic acid. The spectrum was assigned, and the sites of N- and O-sulfation and the conformation of each uronic acid residue were established, with chemical shift data obtained from BASHD-TOCSY spectra, while the sequence of the monosaccharide residues in the octasaccharide was determined from inter-residue NOEs in BASHD-NOESY spectra. Acid dissociation constants were determined for each carboxylic acid group of the octasaccharide, as well as for related tetra- and hexasaccharides, from chemical shift–pD titration curves. Chemical shift–pD titration curves were obtained for each carboxylic acid group from sub-spectra taken from BASHD-TOCSY spectra that were measured as a function of pD. The pKAs of the carboxylic acid groups of the ∆UA(2S) residues are less than those of the IdoA(2S) residues, and the pKAs of the carboxylic acid groups of the IdoA(2S) residues for a given oligosaccharide are similar in magnitude. Relative acidities of the carboxylic acid groups of each oligosaccharide were calculated from chemical shift data by a pH-independent method

Characterisation of Channel Waveguides Fabricated in an Er3+-Doped Tellurite Glass Using Two Ion Beam Techniques

Two methods were proposed and implemented for the fabrication of channel waveguides in an Er-doped Tellurite glass. In the first method, channel waveguides were fabricated by implanting 1.5 MeV and 3.5 MeV energy N+ ions through a special silicon mask to the glass sample at various fluences. Those waveguides implanted at a fluence of 1.0 &times; 1016 ions/cm2 operated up to 980 nm, and showed green upconversion of the Erbium ions. In the second method, channel waveguides were directly written in the Er3+: TeO2W2O3 glass using an 11 MeV C4+ ion microbeam with fluences in the range of 1 &middot; 1014&ndash;5 &middot; 1016 ions/cm2. The waveguides worked in single mode regime up to the 1540 nm telecom wavelength. Propagation losses were reduced from the 14 dB/cm of the as-irradiated waveguides by stepwise thermal annealing to 1.5 dB/cm at &lambda; = 1400 nm

Rapid decrease of malaria morbidity following the introduction of community-based monitoring in a rural area of central Vietnam

<p>Abstract</p> <p>Background</p> <p>Despite a successful control programme, malaria has not completely disappeared in Vietnam; it remains endemic in remote areas of central Vietnam, where standard control activities seem to be less effective. The evolution of malaria prevalence and incidence over two and half years in a rural area of central Vietnam, after the introduction of community-based monitoring of malaria cases, is presented.</p> <p>Methods</p> <p>After a complete census, six cross-sectional surveys and passive detection of malaria cases (by village and commune health workers using rapid diagnostic tests) were carried out between March 2004 and December 2006 in Ninh-Thuan province, in a population of about 10,000 individuals. The prevalence of malaria infection and the incidence of clinical cases were estimated.</p> <p>Results</p> <p>Malaria prevalence significantly decreased from 13.6% (281/2,068) in December 2004 to 4.0% (80/2,019) in December 2006. <it>Plasmodium falciparum </it>and <it>Plasmodium vivax </it>were the most common infections with few <it>Plasmodium malariae </it>mono-infections and some mixed infections. During the study period, malaria incidence decreased by more than 50%, from 25.7/1,000 population at risk in the second half of 2004 to 12.3/1,000 in the second half of 2006. The incidence showed seasonal variations, with a yearly peak between June and December, except in 2006 when the peak observed in the previous years did not occur.</p> <p>Conclusion</p> <p>Over a 2.5-year follow-up period, malaria prevalence and incidence decreased by more than 70% and 50%, respectively. Possibly, this could be attributed to the setting up of a passive case detection system based on village health workers, indicating that a major impact on the malaria burden can be obtained whenever prompt diagnosis and adequate treatment are available.</p

A Multi-Center Randomized Trial to Assess the Efficacy of Gatifloxacin versus Ciprofloxacin for the Treatment of Shigellosis in Vietnamese Children

The bacterial genus Shigella is the most common cause of dysentery (diarrhea containing blood and/or mucus) and the disease is common in developing countries with limitations in sanitation. Children are most at risk of infection and frequently require hospitalization and antimicrobial therapy. The WHO currently recommends the fluoroquinolone, ciprofloxacin, for the treatment of childhood Shigella infections. In recent years there has been a sharp increase in the number of organisms that exhibit resistance to nalidixic acid (an antimicrobial related to ciprofloxacin), corresponding with reduced susceptibility to ciprofloxacin. We hypothesized that infections with Shigella strains that demonstrate resistance to nalidixic acid may prevent effective treatment with ciprofloxacin. We performed a randomized controlled trial to compare 3 day ciprofloxacin therapy with 3 days of gatifloxacin, a newer generation fluoroquinolone with greater activity than ciprofloxacin. We measured treatment failure and time to the cessation of individual disease symptoms in 249 children with dysentery treated with gatifloxacin and 245 treated with ciprofloxacin. We could identify no significant differences in treatment failure between the two groups or in time to the cessation of individual symptoms. We conclude that, in Vietnam, ciprofloxacin and gatifloxacin are similarly effective for the treatment of acute dysentery