Some Variants of the Controlled Random Search Algorithm for Global Optimization

We suggested some modifications to the controlled random search (CRS) algorithm for global optimization. We introduce new trial point generation schemes in CRS, in particular, point generation schemes using linear interpolation and mutation. Central to our modifications is the probabilistic adaptation of point generation schemes within the CRS algorithm.A numerical study is carried out using a set of 50 test problems many of which are inspired by practical applications. Numerical experiments indicate that the resulting algorithms are considerably better than the previous versions. Thus, they offer a reasonable alternative to many currently available stochastic algorithms, especially for problems requiring direct search type methods.     

The Inspiratory Maneuver: A Simple Method to Assess the Superficial Lamina Propria During Endoscopy

We describe a simple means of assessing the condition of the superficial lamina propria during endoscopy, which we use in our practice as an adjunct to careful stroboscopic examination. An intake of breath against partially adducted vocal folds serves to draw the mucosa inferomedially into the glottis, which reveals areas of diminished mobility, the relationship of mucosal lesions to deeper tissues of the vocal folds, and subtle submucosal lesions. This is possible because of the unique geometry of the glottis that renders the vector forces of airflow different at inspiration and expiration. Because the integrity of the superficial lamina propria is essential to healthy phonation, we have found the inspiratory maneuver useful across a wide variety of mucosal pathologic conditions.     

Crystal Structure Investigation of RE–Ni–Zn Ternary Compounds (RE = La,Ce, Tb)

The RENiZn (RE = La, Tb), RE₂Ni₂Zn (RE = La, Ce, Tb) and La₃Ni₃Zn ternary compounds were synthesized by two methods: by heating in a resistance furnace evacuated quartz ampoules containing Al₂O₃‐crucibles with element pieces and by induction melting in sealed Ta crucibles with subsequent annealing at 400 °C. Scanning electron microscopy (SEM) coupled with energy dispersive X‐ray spectroscopy (EDXS) was used for examining microstructure and phase composition of some of the alloys. The crystal structures for all the investigated phases were solved or confirmed on single crystal data by applying the direct methods refined by a standard least square procedure: LaNiZn – str. type ZrNiAl, hexagonal, , hP9, a = 0.7285(1), c = 0.3938(1) nm, wR₂ = 0.0534, 257 F² values, 14 variables; a = 0.7044(1), c = 0.3782(1) nm, wR₂ = 0.0447, 236 F² values, 14 variables for TbNiZn; La₂Ni₂Zn – str. type Pr₂Ni₂Al, orthorhombic, Immm, oI10, a = 0.4381(1), b = 0.5459(1) c = 0.8605(2) nm, wR₂ = 0.0824, 223 F² values, 13 variables; a = 0.4365(1), b = 0.5430(1) c = 0.8279(2) nm, wR₂ = 0.0635, 209 F² values, 13 variables for Ce₂Ni₂Zn; a = 0.4209(1), b = 0.5366(1) c = 0.8165 (1) nm, wR₂ = 0.0757, 200 F² values, 13 variables for Tb₂Ni₂Zn; La₃Ni₃Zn – str. type Y₃Co₃Ga, orthorhombic, Cmcm, oS28, a = 0.4276(1), b = 1.0310(2) c = 1.3636(3) nm, wR₂ = 0.0859, 579 F² values, 26 variables. The structural peculiarities of these compounds and their relations are discussed.     

Oral Breathing Increases Pth and Vocal Effort by Superficial Drying of Vocal Fold Mucosa

Oral breathing superficially dehydrates the airway lumen by decreasing the depth of the sol layer in humans and animals. Conversely, nasal breathing can increase the humidity of inspired air. We compared the effects of short-term oral and nasal breathing on P_th and perceived vocal effort in 20 female subjects randomly assigned to two groups: oral breathing (N = 10, age 21–32 years); nasal breathing (N = 10, age 20–36 years). We hypothesized that short-term oral breathing, but not nasal breathing, would increase P_th, and that subjects would perceive this change as an increase in vocal effort. Following 15 minutes of oral breathing, P_th increased at comfortable and low pitch (p < 0.01) with 6 of 10 subjects reporting increased vocal effort. Nasal breathing reduced P_th at all three pitches (p < 0.01), and 7 of 10 subjects reported decreased vocal effort. Over all subjects, 49% of the variance in treatment-induced change in P_th was accounted for by change in vocal effort (R = 0.70). We posit that obligatory oral breathing places healthy subjects at risk for symptoms of increased vocal effort. The facilitatory role of superficial hydration on vocal fold oscillation should be considered in biomechanical models of phonation and in the clinical prevention of laryngeal dryness.     

Specific Ion and Concentration Effects in Acetate Solutions with Na+, K+ and Cs+

How salt ions affect solutes and the water beyond the solvation shell is not well understood. Molecular dynamics simulations of alkali-acetate solutions were analysed here in order to examine if, and how, different cations and solute concentrations affect the water structure and the interactions between water and acetates. The results revealed that water structure is perturbed to more than 1 nm away from the acetates and that this effect is more pronounced in physiological than in molar electrolyte concentrations. Analysis of simulations of a soluble protein revealed that the water orientation is perturbed to at least 1.5 nm from the protein structure. Furthermore, modifications to the orientation of water around carboxylate side chains were shown to depend on the local environment on the protein surface, and could extend to well over 1 nm, which may have an effect on protein dynamics during MD simulations in small water boxes.     

Hydroxy-Porphyrin as an Effective,Endogenous Molecular Clamp during Early Stages of Amyloid Fibrillization

Amyloid fibril formation of proteins is of great concern in neurodegenerative disease and can be detrimental to the storage and stability of biologics. Recent evidence suggests that insulin fibril formation reduces the efficacy of type II diabetes management and may lead to several complications. To develop anti-amyloidogenic compounds of endogenous origin, we have utilized the hydrogen bond anchoring, π stacking ability of porphyrin, and investigated its role on the inhibition of insulin amyloid formation. We report that hydroxylation and metal removal from the heme moiety yields an excellent inhibitor of insulin fibril formation. Thioflavin T, tyrosine fluorescence, Circular Dichorism (CD) spectroscopy, Field emission scanning electron microscopy (FESEM) and molecular dynamics (MD) simulation studies suggest that hematoporphyrin (HP) having hydrogen bonding ability on both sides is a superior inhibitor compared to hemin and protoporphyrin (PP). Experiments with hen egg white lysozyme (HEWL) amyloid fibril formation also validated the efficacy of endogenous porphyrin based small molecules. Our results will help to decipher a general therapeutic strategy to counter amyloidogenesis.     

Validation of a sensitive and specific LC–MS/MS method and application to evaluate the systemic exposure and bioavailability of glycopyrrolate via different drug delivery approaches/devices

A specific and sensitive LC–MS/MS method using d₃-glycopyrrolate as the internal standard (IS) was developed for the quantitative determination of glycopyrrolate (GLY) in human plasma over a concentration range of 4.00–2000 pg/ml. The GLY and IS were extracted using a solid-phase extraction cartridge, then eluted with 0.5% formic acid in 70:30 acetonitrile–water. The eluate was directly injected into an Agilent Pursuit 5PFP column for analysis using an isocratic mobile phase of 50:50 A:B at a flow-rate of 0.500 ml/min (A, 10 mm ammonium acetate in 1% formic acid; B, methanol). The MS detection was in positive mode by monitoring m/z 318.3 → 116.1 (GLY) and 321.3 → 119.1 (IS). The method validation showed the linearity of r² ≥ 0.9960, intra-/inter-run precisions of ≤11.1% coefficient of variation and accuracies ranging from −2.5 to 12.8% relative error for all levels of quality control samples. This method was successfully employed to support a clinical study to compare absorption and bioavailability of GLY administered by a Magnair^® eFlow nebulizer to a Seebri^® Breezhaler^® with/without a charcoal blockade of gastric absorption. By comparison with intravenous administration, respective bioavailabilities of ~15% for GLY/Magnair and ~22% for the Seebri Breezhaler were found. The bioanalytical reliability was also demonstrated by satisfactory incurred sample reanalysis performance.     

LIQUID CRYSTAL DISPLAY APPLICATIONS: Past,Present & Future

Abstract

At ALCOM's international symposium on 12 – 13 October, 1995, over 100 participants gathered in beautiful Cuyahoga Falls, Ohio, to discuss current developments in dynamics and defects in liquid crystals and to honour Professor Alfred Saupe on the occasion of his 70th birthday. ALCOM, the US National Science Foundation and Technology Center on Advanced liquid Crystalline Optical Materials, is a consortium of Kent State, Case Western Reserve and Akron Universities.     

A Comparison of Two Methods of Formant Frequency Estimation for High-Pitched Voices

This study sought to compare formant frequencies estimated from natural phonation to those estimated using two methods of artificial laryngeal stimulation: (1) stimulation of the vocal tract using an artificial larynx placed on the neck and (2) stimulation of the vocal tract using an artificial larynx with an attached tube placed in the oral cavity. Twenty males between the ages of 18 and 45 performed the following three tasks on the vowels /a/ and /i/: (1) 4 seconds of sustained vowel, (2) 2 seconds of sustained vowel followed by 2 seconds of artificial phonation via a neck placement, and (3) 4 seconds of sustained vowel, the last two of which were accompanied by artificial phonation via an oral placement. Frequencies for formants 1-4 were measured for each task at second 1 and second 3 using linear predictive coding. These measures were compared across second 1 and second 3, as well as across all three tasks. Neither of the methods of artificial laryngeal stimulation tested in this study yielded formant frequency estimates that consistently agreed with those obtained from natural phonation for both vowels and all formants. However, when estimating mean formant frequency data for samples of large N, each of the methods agreed with mean estimations obtained from natural phonation for specific vowels and formants. The greatest agreement was found for a neck placement of the artificial larynx on the vowel /a/.