An empirical analysis of consumers' attitudes toward pharmacies' advertising.

This study investigates current attitudes and opinions toward pharmacies' advertising. The purposes of this study were to determine (a) consumers' attitudes toward advertising by pharmacies and (b) whether age, race, income, marital status, occupation, education, sex, and number of children in household of the consumer accounted for any significant difference in attitudes toward pharmacies that advertise. The intent was to discover information that would be useful to pharmacies in planning marketing strategies and improving the quality of their advertising. The study seems to confirm the belief of many pharmacies that advertising and marketing clearly have a place in the future of pharmacists' services.

An empirical analysis of ethical and professional issues in physicians' advertising: A comparative cross-sectional study.

The purpose of this study is to investigate current attitudes and opinions of physicians' advertising and to compare them to the attitudes expressed 10 years previously. This study was designed to determine (a) consumers' attitudes toward advertising by physicians, and (b) whether age, occupation, income, education, or sex of consumer accounted for any significant difference in attitudes toward physicians who advertise. The study seems to confirm the belief of many marketing professionals that advertising and marketing do not have a place in the management and operation of professional services.

An empirical analysis of the public's attitudes toward advertising hospital services: a comparative cross-sectional study.

This study investigates current opinions about hospital advertising and compares them to the attitudes expressed 25 years ago. It replicates a survey done in 1985, using the same questionnaire and population to compare responses longitudinally. The study indicates some changes in the public's opinions of hospital advertising. Although the image of hospitals remains positive, most of the 2010 respondents' opinions were rather mixed regarding whether it is proper for hospitals to advertise. The study also confirmed that the quality of service and reputation of hospitals remain more important to the public than price.

Mutations in the 70K peroxisomal membrane protein gene in Zellweger syndrome.

The peroxisomal membrane protein, with a relative molecular mass of 70,000 (M(r) 70K) (PMP70), is an important component of peroxisomal membranes and an ATP-binding cassette protein. To investigate its possible involvement in Zellweger syndrome (ZS), an inborn error of peroxisome assembly, we cloned and sequenced cDNAs for human PMP70 and mapped the gene to chromosome 1. Amongst 32 probands with ZS or related disorders, we found two mutant PMP70 alleles in single ZS probands from the same complementation group. One allele has a donor splice site mutation and the second a missense mutation. Our results suggest that PMP70 plays an important role in peroxisome biogenesis and that mutations in PMP70 may be responsible for a subset of ZS patients.

Human PEX7 encodes the peroxisomal PTS2 receptor and is responsible for rhizomelic chondrodysplasia punctata.

Rhizomelic chondrodysplasia punctata (RCDP) is a rare autosomal recessive phenotype that comprises complementation group 11 of the peroxisome biogenesis disorders (PBD). PEX7, a candidate gene for RCDP identified in yeast, encodes the receptor for peroxisomal matrix proteins with the type-2 peroxisome targeting signal (PTS2). By homology probing we identified human and murine PEX7 genes and found that expression of either corrects the PTS2-import defect characteristic of RCDP cells. In a collection of 36 RCDP probands, we found two inactivating PEX7 mutations: one, L292ter, was present in 26 of the probands, all with a severe phenotype; the second, A218V, was present in three probands, including two with a milder phenotype. A third mutation, G217R, whose functional significance is yet to be determined, was present in five probands, all compound heterozygotes with L292ter. We conclude that PEX7 is responsible for RCDP (PBD CG11) and suggest a founder effect may explain the high frequency of L292ter.

Isolation of the human PEX12 gene, mutated in group 3 of the peroxisome biogenesis disorders.

The peroxisome biogenesis disorders (PBDs) are a group of genetically heterogeneous diseases lethal in early infancy. Although the clinical features of PBD patients may vary, cells from all PBD patients exhibit a defect in the import of one or more classes of peroxisomal matrix proteins. This cellular phenotype is shared by yeast pex mutants, and human orthologues of yeast PEX genes have been shown to be defective in some groups of PBD patients. We identified a putative human orthologue of ScPEX12 by screening the database of expressed sequence tags for cDNAs capable of encoding a protein similar to yeast Pex12p. Although its sequence similarity to yeast Pex12 proteins was limited, PEX12 shared the same subcellular distribution as yeast Pex12p and localized to the peroxisome membrane. PEX12 expression restored peroxisomal protein import in fibroblasts from PBD patients of complement group 3 (CG3) and frameshift mutations in PEX12 were detected in two unrelated CG3 patients. These data demonstrate that mutations in PEX12 are responsible for CG3 of the PBD and that PEX12 plays an essential role in peroxisomal matrix protein import.

Mutations in the PTS1 receptor gene, PXR1, define complementation group 2 of the peroxisome biogenesis disorders.

The peroxisome biogenesis disorders (PBDs) are lethal recessive diseases caused by defects in peroxisome assembly. We have isolated PXR1, a human homologue of the yeast P. pastoris PAS8 (peroxisome assembly) gene. PXR1, like PAS8, encodes a receptor for proteins with the type-1 peroxisomal targeting signal (PTS1). Mutations in PXR1 define complementation group 2 of PBDs and expression of PXR1 rescues the PTS1 import defect of fibroblasts from these patients. Based on the observation that PXR1 exists both in the cytosol and in association with peroxisomes, we propose that PXR1 protein recognizes PTS1-containing proteins in the cytosol and directs them to the peroxisome.

Mutations in PEX1 are the most common cause of peroxisome biogenesis disorders.

The peroxisome biogenesis disorders (PBDs) are a group of lethal autosomal-recessive diseases caused by defects in peroxisomal matrix protein import, with the concomitant loss of multiple peroxisomal enzyme activities. Ten complementation groups (CGs) have been identified for the PBDs, with CG1 accounting for 51% of all PBD patients. We identified the human orthologue of yeast PEX1, a gene required for peroxisomal matrix protein import. Expression of human PEX1 restored peroxisomal protein import in fibroblasts from 30 CG1 patients, and PEX1 mutations were detected in multiple CG1 probands. A common PEX1 allele, G843D, is present in approximately half of CG1 patients and has a deleterious effect on PEX1 activity. Phenotypic analysis of PEX1-deficient cells revealed severe defects in peroxisomal matrix protein import and destabilization of PEX5, the receptor for the type-1 peroxisomal targetting signal, even though peroxisomes were present in these cells and capable of importing peroxisomal membrane proteins. These data demonstrate an important role for PEX1 in peroxisome biogenesis and suggest that mutations in this gene are the most common cause of the PBDs.

Wafer scale manufacturing of high precision micro-optical components through X-ray lithography yielding 1800 Gray Levels in a fingertip sized chip.

We present a novel x-ray lithography based micromanufacturing methodology that offers scalable manufacturing of high precision optical components. It is accomplished through simultaneous usage of multiple stencil masks made moveable with respect to one another through custom made micromotion stages. The range of spectral flux reaching the sample surface at the LiMiNT micro/nanomanufacturing facility of Singapore Synchrotron Light Source (SSLS) is about 2 keV to 10 keV, offering substantial photon energy to carry out deep x-ray lithography. In this energy range, x-rays penetrate through resist materials with only little scattering. The highly collimated rectangular beam architecture of the x-ray source enables a full 4″ wafer scale fabrication. Precise control of dose deposited offers determined chain scission in the polymer to required depth enabling 1800 discrete gray levels in a chip of area 20 mm2 and with more than 2000 within our reach. Due to its parallel processing capability, our methodology serves as a promising candidate to fabricate micro/nano components of optical quality on a large scale to cater for industrial requirements. Usage of these fine components in analytical devices such as spectrometers and multispectral imagers transforms their architecture and shrinks their size to pocket dimension. It also reduces their complexity and increases affordability while also expanding their application areas. Consequently, equipment based on these devices is made available and affordable for consumers and businesses expanding the horizon of analytical applications. Mass manufacturing is especially vital when these devices are to be sold in large quantities especially as components for original equipment manufacturers (OEM), which has also been demonstrated through our work. Furthermore, we also substantially improve the quality of the micro-components fabricated, 3D architecture generated, throughput, capability and availability for industrial application. Manufacturing 1800 Gray levels or more through other competing techniques is either limited due to multiple process steps involved or due to unacceptably long time required owing to their pencil beam architecture. Our manufacturing technique presented here overcomes both these shortcomings in terms of the maximum number of gray levels that can be generated, and the time required to generate the same.

Radiation-induced melting in coherent X-ray diffractive imaging at the nanoscale.

Coherent X-ray diffraction techniques play an increasingly significant role in the imaging of nanoscale structures, ranging from metallic and semiconductor to biological objects. In material science, X-rays are usually considered to be of a low-destructive nature, but under certain conditions they can cause significant radiation damage and heat loading on the samples. The qualitative literature data concerning the tolerance of nanostructured samples to synchrotron radiation in coherent diffraction imaging experiments are scarce. In this work the experimental evidence of a complete destruction of polymer and gold nanosamples by the synchrotron beam is reported in the case of imaging at 1-10 nm spatial resolution. Numerical simulations based on a heat-transfer model demonstrate the high sensitivity of temperature distribution in samples to macroscopic experimental parameters such as the conduction properties of materials, radiation heat transfer and convection. However, for realistic experimental conditions the calculated rates of temperature rise alone cannot explain the melting transitions observed in the nanosamples. Comparison of these results with the literature data allows a specific scenario of the sample destruction in each particular case to be presented, and a strategy for damage reduction to be proposed.

Multichannel Fourier-transform interferometry for fast signals.

Multichannel Fourier transform interferometry to measure the spectrum of arbitrarily short pulses and of fast time-varying signals was achieved using a micro/nanomanufactured multimirror array. We describe the performance of a demonstrator FTIR that works in the mid-infrared (MIR) range of 700-1400 cm(-1) and reaches a spectral resolution of 10 cm(-1) taking into account apodization. Spectral measurements down to pulse lengths of 319 µs were carried out using a mechanical camera shutter. Arbitrarily short pulses are expected feasible provided the source can deliver enough photons to overcome the noise equivalent number of photons.

Multivariate analysis techniques in the forensics investigation of the postblast residues by means of Fourier transform-infrared spectroscopy.

Fourier transform-infrared (FT-IR) spectroscopy has gained considerable attention among the forensic scientists because it shows high sensitivity and selectivity and offers near real time detection of analyzed samples. However, the amount of obtained information due to complexity of the measured spectra forces the use of additional data processing. Application of the multivariate statistical techniques for the analysis of the FT-IR data seems to be necessary in order to enable feature extraction, proper evaluation, and identification of obtained spectra. In this article, an attempt to develop a feasible procedure for characterization of spectroscopic signatures of the explosive materials in the remnants after explosion has been made. All spectra were derived after analysis of samples from debris after especially prepared and performed blasts with the use of three various highly explosive materials: C-4, 2,4,6-trinitrotoluene (TNT), and pentaerythritol tetranitrate (PETN). Two well-known multivariate statistical methods, hierarchical cluster analysis (HCA) and principal component analysis (PCA), were tested in order to classify the samples into separate classes using a broad wavelength data range (4000-600 cm(-1)) on collected spectra sets. After many trials it seems that PCA is the best choice for the mentioned earlier tasks. It was found that only three principal components carry over 99.6% of variance within the sample set. The results show that FT-IR spectroscopy in combination with multivariate methods is well-suited for identification and differentiation purposes even in quite large data sets, and for that reason forensic laboratories could employ these methods for rapid screening analysis.

All-metal self-supported THz metamaterial--the meta-foil.

Modern metamaterials face functional constraints as they are commonly embedded in or deposited on dielectric materials. We provide a new solution by microfabricating a completely free-standing all-metal self-supported metamaterial. Using upright S-string architecture with the distinctive feature of metallic transverse interconnects, we form a locally stiff, globally flexible space-grid. Infrared Fourier transform interferometry reveals the typical double-peak structure of a magnetically excited left-handed and an electrically excited right-handed pass-band that is maintained under strong bending and heating, and is sensitive to dielectrics. Exploiting UV/X-ray lithography and ultimately plastic moulding, meta-foils can be mass manufactured cost-effectively to serve as optical elements.

Subcellular localization of creatine kinase in Torpedo electrocytes: association with acetylcholine receptor-rich membranes.

Creatine kinase (CK, EC 2.7.3.2) has recently been identified as the intermediate isoelectric point species (pl 6.5-6.8) of the Mr 40,000-43,000 nonreceptor, peripheral v-proteins in Torpedo marmorata acetylcholine receptor-rich membranes (Barrantes, F. J., G. Mieskes, and T. Wallimann, 1983, Proc. Natl. Acad. Sci. USA, 80: 5440-5444). In the present study, this finding is substantiated at the cellular and subcellular level of the T. marmorata electric organ by immunofluorescence and by protein A-gold labeling of either ultrathin cryosections of electrocytes or purified receptor-membrane vesicles that use subunit-specific anti-chicken creatine kinase antibodies. The muscle form of the kinase, on the one hand, is present throughout the entire T. marmorata electrocyte except in the nuclei. The brain form of the kinase, on the other hand, is predominantly located on the ventral, innervated face of the electrocyte, where it is closely associated with both surfaces of the postsynaptic membrane, and secondarily in the synaptic vesicles at the presynaptic terminal. Labeling of the noninnervated dorsal membrane is observed at the invaginated sac system. In the case of purified acetylcholine receptor-rich membranes, antibodies specific for chicken B-CK label only one face of the isolated vesicles. No immunoreaction is observed with anti-chicken M-CK antibodies. A discussion follows on the possible implications of these localizations of creatine kinase in connection with the function of the acetylcholine receptor at the postsynaptic membrane, the Na/K ATPase at the dorsal electrocyte membrane, and the ATP-dependent transmitter release at the nerve ending.

Sequence-specific cleavage of double helical DNA by triple helix formation.

Homopyrimidine oligodeoxyribonucleotides with EDTA-Fe attached at a single position bind the corresponding homopyrimidine-homopurine tracts within large double-stranded DNA by triple helix formation and cleave at that site. Oligonucleotides with EDTA.Fe at the 5' end cause a sequence specific double strand break. The location and asymmetry of the cleavage pattern reveal that the homopyrimidine-EDTA probes bind in the major groove parallel to the homopurine strand of Watson-Crick double helical DNA. The sequence-specific recognition of double helical DNA by homopyrimidine probes is sensitive to single base mismatches. Homopyrimidine probes equipped with DNA cleaving moieties could be useful tools for mapping chromosomes.

Ceramidase deficiency in Farber's disease (lipogranulomatosis).

Ceramidase activity could not be demonstrated in the kidney and cerebellum from a deceased patient with Farber's disease, whereas the activities of six control acid hydrolase enzymes appeared normal. This enzyme defect presumably accounts for the accumulation that has been described in two patients and may represent the biochemical basis of this disorder.

Prolonged survival and remyelination after hematopoietic cell transplantation in the twitcher mouse.

The twitcher mouse is an animal model of galactosylceramidase deficiency (Krabbe's disease), a human sphingolipidosis. The effects of hematopoietic cell transplantation as potential enzyme replacement therapy were examined in the twitcher mouse. Survival in twitcher mice with transplants was significantly prolonged and was associated with gradual repair of demyelination in peripheral nerves. In contrast, there was no improvement in the neurodegenerative process in the central nervous system after transplantation. These observations indicate that cellular transplantation may effectively provide in vivo enzyme replacement for the peripheral manifestations of genetic storage diseases. Strategies to perturb the blood-brain barrier may be necessary for enzyme replacement to be therapeutic in diseases with central nervous system manifestations.

Peroxisomal defects in neonatal-onset and X-linked adrenoleukodystrophies.

Accumulation of very long chain fatty acids in X-linked and neonatal forms of adrenoleukodystrophy (ALD) appears to be a consequence of deficient peroxisomal oxidation of very long chain fatty acids. Peroxisomes were readily identified in liver biopsies taken from a patient having the X-linked disorder. However, in liver biopsies from a patient having neonatal-onset ALD, hepatocellular peroxisomes were greatly reduced in size and number, and sedimentable catalase was markedly diminished. The presence of increased concentrations of serum pipecolic acid and the bile acid intermediate, trihydroxycoprostanic acid, in the neonatal ALD patient are associated with a generalized diminution of peroxisomal activities that was not observed in the patient with X-linked ALD.

A PEX10 defect in a patient with no detectable defect in peroxisome assembly or metabolism in cultured fibroblasts.

Zellweger spectrum disorders (ZSD) are diagnosed by biochemical assay in blood, urine and cultured fibroblasts and PEX gene mutation identification. In most cases studies in fibroblasts corroborate results obtained in body fluids. In 1996 Clayton and colleagues described a 10-year old girl with evidence of a peroxisome disorder, based on elevated bile acid metabolites and phytanate. At the time it was not possible to distinguish whether she had a ZSD or a single peroxisomal protein defect. Studies in our laboratory showed that she also had elevated plasma pipecolate, supporting the former diagnosis. Despite the abnormal metabolites detected in blood (phytanate, bile acid intermediates and pipecolate), analysis of multiple peroxisomal pathways in fibroblasts yielded normal results. In addition, she had a milder clinical phenotype than usually associated with ZSD. Since complementation analysis to determine the gene defect was not possible, we screened this patient following the PEX Gene Screen algorithm (PGS). The PGS provides a template for sequencing PEX gene exons independent of complementation analysis. Two mutations in PEX10 were identified, a frameshift mutation inherited from her father and a de novo missense mutation in a conserved functional domain on the other allele. This case highlights that molecular analysis may be essential to the diagnosis of patients at the milder end of the ZSD spectrum. Furthermore, it supports the concept that some tissues are less affected by certain PEX gene defects than brain and liver.

Free-standing THz electromagnetic metamaterials.

Using micromanufactured S-shaped gold strings suspended in free space by means of window-frames, we experimentally demonstrate an electromagnetic meta-material (EM(3)) in which the metallic structures are no longer embedded in matrices or deposited on substrates such that the response is solely determined by the geometrical parameters and the properties of the metal. Two carefully aligned and assembled window-frames form a bi-layer chip that exhibits 2D left-handed pass-bands corresponding to two different magnetic resonant loops in the range of 1.4 to 2.2 THz as characterized by Fourier transform interferometry and numerical simulation. Chips have a comparably large useful area of 56 mm(2). Our results are a step towards providing EM(3) that fulfill the common notions of a material.