Morphology-Controlled Coating of Colloidal Particles with Silica: Influence of Particle Surface Functionalization.

We present a general, convenient, and efficient synthetic concept for the coating of colloidal particles with a silica (SiO2) shell of well-defined and precisely controlled morphology and porosity. Monodisperse submicroscopic polystyrene (PS) particles were synthesized via two-stage emulsifier-free emulsion polymerization and subsequent swelling polymerization, enabling selective particle surface modification by the incorporation of ionic (methacrylic acid, MAA) or nonionic (hydroxyethyl methacrylate, HEMA or methacrylamide, MAAm) comonomers, which could be proven by zeta potential measurements as well as by determining the three-phase contact angle of the colloidal particles adsorbed at the air-water and n-decane-water interface. The functionalized particles could be directly coated with silica shells of variable thickness, porosity, and controlled surface roughness in a seeded sol-gel process from tetraethoxysilane (TEOS), leading to hybrid PS@silica particles with morphologies ranging from core-shell (CS) to raspberry-type architectures. The experimental results demonstrated that the silica coating could be precisely tailored by the type of surface functionalization, which strongly influences the surface properties of the colloidal particles and thus the morphology of the final silica shell. Furthermore, the PS cores could be easily removed by thermal treatment, yielding extremely uniform hollow silica particles, while maintaining their initial shell architecture. These particles are highly stable against irreversible aggregation and could be readily dried, purified, and redispersed in various solvents. Herein we show a first example of coating semiconducting CdSe/ZnS nanocrystals with smooth and spherical silica shells by applying the presented method that are expected to be suitable systems for applications as markers in biology and life science by using fluorescence microscopy methods, which are also briefly discussed.

Free-space optical communications research and demonstrations at the U.S. Naval Research Laboratory.

Free-space optical communication can allow high-bandwidth data links that are hard to detect, intercept, or jam. This makes them attractive for many applications. However, these links also require very accurate pointing, and their availability is affected by weather. These challenges have limited the deployment of free-space optical systems. The U.S. Naval Research Laboratory has, for the last 15 years, engaged in research into atmospheric propagation and photonic components with a goal of characterizing and overcoming these limitations. In addition several demonstrations of free-space optical links in real-world Navy applications have been conducted. This paper reviews this work and the principles guiding it.

Reduction of scintillation in optical modulating retro-reflector links.

Optical modulating retro-reflectors enable free-space optical links that have greatly reduced pointing requirements and do not require a laser at one end of the link. However, these types of links can exhibit very high optical scintillation due to the double passage of the beam through the atmosphere. This high scintillation causes fades and surges that can lead to packet errors in the link. It is shown that scintillation can be greatly reduced through a combination of techniques including retro-reflector diversity, aperture averaging and bistatic optical interrogation. Improvements of 20 dB in link performance are demonstrated.

Fully reversible shape transition of soft spheres in elastomeric polymer opal films.

Core-interlayer-shell (CIS) beads featuring noncross-linked hard cores were used to prepare large and well-defined elastomeric opal films with remarkably distinct iridescent reflection colors. The matrix of the opal films was cross-linked by UV-irradiation after compression molding of the CIS beads mixed with a bifunctional monomer. Stress-induced deformation of the embedded PS cores lead to hexagonally arranged spheroid oblates with an aspect ratio of 2.5. Optical characterization shows that bead deformation provokes a tremendous photonic band gap shift of about 160 nm. Fully reversible shape transition from the spheroid oblates back to the spherical beads and hence full recovery of the original photonic band gap can be achieved.

One year failure rate for de-novo ventriculo-peritoneal shunts in children from a small volume paediatric neurosurgical unit.

It is the belief of some that results of shunt surgery for the treatment of hydrocephalus in children are improved if the surgery is performed in high-volume centres. Currently in the UK paediatric neurosurgery is undergoing a service review. As part of this review a set of standards of care are being drafted which state that 1-year failure rates and infection rates for de-novo ventriculo-peritoneal shunts in children should be less than 40% and 10%, respectively. Our de-novo shunt infection rate (4.3%) and our 1-year failure rate (28.6%) are well within the standards set by this process and comparable to published literature from much higher volume centres.

Gravity as a factor of aggregative stability and coagulation.

Gravity is a potential factor of aggregative stability and/or coagulation for any heterogeneous system having a density contrast between the dispersed phase and its dispersion medium. However, gravity becomes comparable to other stability factors only when the particle size becomes large enough. Since the particle size may grow in time due to various other instabilities, even nano-systems may eventually become susceptible to gravity. There have been many attempts in the last century to incorporate gravity in the overall theory of aggregative stability, but the relevant papers are scattered over a wide variety of journals, some of which are very obscure. Reviews on this subject in modern handbooks are scarce and inadequate. No review describes the role of gravity at all three levels introduced by DLVO theory for characterizing aggregative stability, namely: particle pair interaction, collision frequency and population balance equation. Furthermore, the modern tendency towards numerical solutions overshadows existing analytical solutions. We present a consistent review at each DLVO level. First we describe the role of gravity in particle pair interactions, including both available analytical solutions as well as numerical stability diagrams. Next we discuss a number of works on collision frequency, including works for both charged and non-charged particles. Finally, we present analytical solutions of the population balance equation that takes gravity into account and then compare these analytical solutions with numerical solutions. In addition to the traditional aggregate model we also discuss work on a fractal model and its relevance to gravity controlled stability. Finally, we discuss many experimental works and their relationship to particular theoretical predictions.

Polymorphisms of dopamine-beta-hydroxylase in ADHD children.

ADHD is a multifactorial disorder clinically characterized by inattentiveness, impulsivity and hyperactivity. The occurrence of this disorder varies between 3 and 6% of the child population, with boys predominating over girls at a ratio of 3 : 1 or more. Dysfunction or imbalance between the dopaminergic and noradrenergic systems of neurotransmitters can play a key role in the ADHD pathophysiology. Alteration of the dopamine/noradrenaline levels can result in hyperactivity. DBH is an enzyme responsible for the conversion of dopamine into noradrenaline. The DBH protein is released in response to stimulation. DBH activity, derived largely from sympathetic nerves, can be measured in human plasma. Patients with ADHD showed decreased activities of DBH in serum and urine. Low DBH levels correlate indirectly with the seriousness of the hyperkinetic syndrome in children (Galvin et al., 1995, 1997). In the DBH gene, the G444A, G910T, C1603T, C1912T, C-1021T, 5'-ins/del and TaqI polymorphisms occur frequently and may affect the function of gene products or modify gene expression and thus influence the progression of ADHD. This article reviews the DBH itself and polymorphisms in the DBH gene that influence the DBH activity in the serum and the CSF level of DBH. All those are evaluated in connection with ADHD.

[History of medical genetics in the Czech Republic]. / Historie lékarské genetiky v Ceské republice.

History of the medical genetics in Bohemia since the period of Mendel is described. Effects of the abuse of genetics in Germany before and during the Second Word War as well as consequences of the liquidation of genetics in the postwar Russia on the development of genetics and the activity of geneticist in the Czech countries are documented. The paper gives information on the progress of modern Czech medical genetics, the role of the Society of Medical Genetics of the Czech Medical Association and the credit the eminent geneticist achieved in the organization and advancement of this specialization. The network of genetic laboratories and the list of available services in the Czech Republic are described in the context of model health care in contemporary Europe.

Large-scale ordering of nanoparticles using viscoelastic shear processing.

Despite the availability of elaborate varieties of nanoparticles, their assembly into regular superstructures and photonic materials remains challenging. Here we show how flexible films of stacked polymer nanoparticles can be directly assembled in a roll-to-roll process using a bending-induced oscillatory shear technique. For sub-micron spherical nanoparticles, this gives elastomeric photonic crystals termed polymer opals showing extremely strong tunable structural colour. With oscillatory strain amplitudes of 300%, crystallization initiates at the wall and develops quickly across the bulk within only five oscillations. The resulting structure of random hexagonal close-packed layers is improved by shearing bidirectionally, alternating between two in-plane directions. Our theoretical framework indicates how the reduction in shear viscosity with increasing order of each layer accounts for these results, even when diffusion is totally absent. This general principle of shear ordering in viscoelastic media opens the way to manufacturable photonic materials, and forms a generic tool for ordering nanoparticles.

Fluorescent multiplex PCR--fast method for autosomal dominant spinocerebellar ataxias screening.

Expansion of CAG trinucleotide repeats has been shown to cause a number of autosomal dominant spinocerebellar ataxias such as SCA1, SCA2, SCA3/MJD, SCA6 and SCA7. These disorders are characterized by a wide inter- and intrafamiliar variation in clinical features. The same mutation can result in different phenotypes and the very similar phenotypes can be caused by different mutations. Therefore it is necessary to investigate more SCA genes (according to prevalence) to identify the causal elongation. We developed a fast and efficient screening method based on touchdown multiplex PCR with fluorescent labelled primers for the most common types of SCAs (SCA 1, 2, 3 and 7). It has been reliable in 113 probands tested. Fragment analysis was performed by using 6% denaturing polyacrylamide gel and employing the automated DNA sequencer. This method considerably shortens the process of molecular genetic screening of SCAs and might be used as a tip for designing other SCA screening sets.

[Expression of PAX2 and PAX8 genes in conventional type of renal carcinoma and their role in the tumor prognosis]. / Exprese genu PAX2 a PAX8 v konvencním typu renálního karcinomu a jejich role v prognostice tohoto onemocnení.

BACKGROUND: Sporadic renal cell carcinoma is one of the most common kidney malignancies in adults (85%). According to the IARC (The International Agency of Research on Cancer) Czech Republic has the first world position in the incidence and mortality for RCC. The prognosis of RCC is very poor because of high mortality around 70 to 50% and unpredictable progression after tumor removal. More precise molecular prognostic markers are required. Genes PAX2 and PAX8 control cell division during embryonic development and plays crucial role in tumor development because of stimulation of cell proliferation and/or inhibition of apoptotic program. METHODS AND RESULTS: Our RCC sample collection contains 64 tumor samples and 10 "normal" renal samples extracted from the affected kidney. mRNA was isolated from all samples and converted into cDNA. Expression of PAX genes was analyzed by using relative quantification real-time PCR with TaqMan labelled probe and GAPDH gene as an endogenous control. CONCLUSIONS: Expression of PAX2 gene was found in 97% and expression of PAX8 gene was found in 89% of analyzed tumor samples. The expression of both target genes was found in all "normal" renal samples. The level of expression of both PAX genes was very variable with the range from hundred times lower to forty times higher in comparison with the expression of chosen endogenous control. There were found no correlations between the expression of target genes and clinical-histological markers. These results do not have prognostic value yet because of short duration of patient observation. Follow-up clinical data are essential for completion of this research.

Methylation changes in promoter and enhancer regions of the WT1 gene in Wilms' tumours.

Although the WT1 gene has been implicated in the aetiology of Wilms' tumour, mutations in WT1 are found only in minority of the tumours. DNA methylation of regulatory elements represents another possibility of modulation of gene expression. We studied methylation in the promoter and enhancer regions of the WT1 gene in 34 Wilms' tumour patients by the polymerase chain reaction on HpaII-digested DNA and by the bisulphite method. No methylation was detected in the promoter region in either tumour or normal kidney or blood DNA samples. In contrast, a HpaII site in the enhancer region was at least partially methylated in normal kidney and blood DNA samples and in about one-third of the tumours, while the majority of tumours showed no methylation. The differential methylation in the enhancer region of the WT1 gene may indicate that methylation of this element can play a role in the regulation of this gene.

Molecular analysis of chromosome 21 in a patient with a phenotype of Down syndrome and apparently normal karyotype.

Down syndrome (DS) is caused in most cases by the presence of an extra chromosome 21. It has been shown that the DS phenotype is produced by duplication of only a small part of the long arm of chromosome 21, the 21q22 region, including and distal to locus D21S55. We present molecular investigations on a woman with clinically typical DS but apparently normal chromosomes. Her parents were consanguineous and she had a sister with a DS phenotype, who died at the age of 15 days. Repeated cytogenetic investigations (G-banding and high resolution banding) on the patient and her parents showed apparently normal chromosomes. Autoradiographs of quantitative Southern blots of DNAs from the patient, her parents, trisomy 21 patients, and normal controls were analyzed after hybridization with unique DNA sequences regionally mapped on chromosome 21. Sequences D21S59, D21S1, D21S11, D21S8, D21S17, D21S55, ERG, D21S15, D21S112, and COL6A1 were all found in two copies. Fluorescent in situ hybridization with a chromosome 21-specific genomic library showed no abnormalities and only two copies of chromosome 21 were detected. Nineteen markers from the critical region studied with polymerase chain reaction amplification of di- and tetranucleotide repeats did not indicate any partial trisomy 21. From this study we conclude that the patient does not have any partial submicroscopic trisomy for any segment of chromosome 21. It seems reasonable to assume that she suffers from an autosomal recessive disorder which is phenotypically indistinguishable from DS.

Acoustic and electroacoustic spectroscopy for characterizing concentrated dispersions and emulsions.

We describe two different techniques (acoustics and electroacoustics), both of which employ ultrasound instead of light for extracting information about the properties of liquid-based dispersions. Ultrasound can propagate through samples that are not transparent for light, which open up many new applications not possible with classical light scattering methods. Acoustic and electroacoustic techniques offer a unique opportunity to characterize concentrated dispersion, emulsions and microemulsions in their natural states. Elimination of a dilution step required for most other techniques (light scattering, sedimentation, electrophoresis) is crucial for an adequate characterization of liquid dispersions, especially when the high concentration leads to structured systems. As with any macroscopic method, ultrasonic techniques characterize the sample in two steps. The first step is to measure some macroscopic property. The second step involves some theoretical treatment of the measured raw data which yields the desired information. Acoustic spectroscopy deals with measuring the attenuation of ultrasound within a certain frequency range. Electroacoustic spectroscopy has two implementations depending on the driving force. We emphasize here on the so-called Colloid Vibration Current (CVI) which is generated by the sound wave as it passes through the dispersion. A review of the theoretical basis of acoustics and electroacoustics is given, with emphasis on models that have been applied to concentrated systems. Recently, new theories have been developed for both acoustics and electroacoustics using a 'coupled phase model' and 'cell model concept'. The coupled phase model is widely used for describing a relative motion of the particles and liquid in the sound wave. The cell model approach opens the way to include both particle-particle interactions and polydispersity into the theoretical model. Experimental evidence is presented that shows that this new approach is successful in concentrated systems up to 45% vol. A short review of the possible applications of acoustics and electroacoustics measurements to a range of systems is presented including: ceramics, mixed dispersed systems, chemical-mechanical polishing abrasives, emulsions, microemulsions and latex materials.

Relationship between experimental results in mammals and man. II. Cytogenetic analysis of bone-marrow cells after treatment of cytembena and cyclophosphamide- cytembena combination.

Cytogenetic analysis and the micronucleus test of bone-marrow cells was used to study the possible extrapolation of results from experimental animals to man. Cytembena was given i.p. in doses of 5, 10, 20, 40 and 80 mg/kg body wt. to Wistar rats and in doses of 20, 40 and 80 mg/kg body wt. to ICR mice and to Chinese hamsters. Five patients with various types of malignancy, so far medically untreated, received 20 mg Cytembena/kg body wt i.v. A combination of Cytembena and cylophosphamide was applied i.p. in single equal doses 1 : 1 of 5,10, 20, and 40 mg/kg body wt to ICR mice, Chinese hamsters and Wistar rats. Patients were given i.v. 20 mg Cytembena and 20 mg cyclophosphamide/kg body wt. Bone-marrow cells were examined 24 h after the administration. The frequency of abnormal metaphases and chromosomal breaks after Cytembena treatment was low; nonetheless, the indicated dose-effect relationship was found in all the rodents used. The frequency of chromosomal breaks was 2--3 times higher in rodents in comparison with man, after treatment with a dose of 20 mg Cytembena/kg body wt. Highest frequencies of induced aberrations were found in mice. The rodents appeared to be 3--4 times more sensitive to the induction of chromosomal breaks and abnormal metaphases than man, after a dose of 20 mg Cytembena and 20 mg cyclophosphamide/kg body wt. The micronucleus test may be regarded as a screening method for assessing mutagenic activity of chemical compounds. Chromosomal analysis and the micronucleus test were about equally convincing in detecting mutagenic effects even with the lowest doses of drugs used. However, the dose-effect relationship was more pronounced in chromosomal aberrations than in the micronucleus test.

The importance of blast cell DNA content for prognosis of childhood acute lymphoblastic leukemia.

The prognostic value of cellular DNA content measured by static cytophotometry was evaluated in 69 children with acute lymphoblastic leukemia (ALL) using the pretreatment distribution of the DNA content in blast cells of bone marrow and peripheral blood. The median follow-up of the whole group of patients was 45 months. Aneuploidy was detected in 71% of children, most of them showing a hyperdiploid content (DNA index greater than 1.05). The duration of complete remission was significantly longer in patients with distinct hyperdiploid DNA content (DNA index greater than 1.16) than in those with less hyperdiploid and diploid DNA content (DNA index less than 1.16). The results achieved by static cytophotometry were compared with flow cytometry analysis and with cytogenetic investigations of chromosomal abnormalities in leukemic cells. Higher correlation was found between flow cytometry and cytogenetics. Flow cytometry proved to be a more convenient method for detection of the DNA content in leukemic cells than static cytophotometry.

Oncogene amplification and expression in pediatric solid tumors.

Oncogene amplification and expression and their mutual relationship was analyzed in 92 pediatric tumors by Southern and Northern blot hybridization with N-MYC, ERB A, ERB B, N-RAS and Shb probes. Amplification and overexpression was associated with more advanced clinical stages of tumor, especially in neuroblastomas, rhabdomyosarcomas and ganglioneuroblastomas. The most frequent alteration observed was N-MYC amplification together with overexpression. N-RAS amplification was not detected, while the overexpression of this oncogene was found in 3 cases. Neither amplification nor overexpression was revealed in any specimen of hepatoblastoma or hepatocellular carcinoma. We suggest that oncogenes overexpression provides more accurate prognostic information than amplification.

Clastogenicity and sister chromatid exchange induction by ftorafur.

The main effect of Ftorafur at the chromosomal level is the induction of chromatid and chromosome breaks, which is some pronounced in neoplastic or transformed cells than in normal cells. Different cell lines used in the study exhibited both in vitro and in vivo varying sensitivity to Ftorafur. Ftorafur does not increase the frequency of SCE.

Can ataxin-2 be down-regulated by allele-specific de novo DNA methylation in SCA2 patients?

Spinocerebellar ataxia type 2 (SCA2) is caused by a CAG trinucleotide repeat expansion within the coding region of the ataxin-2 gene. Affected individuals typically have between 34 and 57 CAG repeats. Signs of the disorder generally begin in adulthood and include progressive ataxia, dysarthria, tremor, hyporeflexia, and slow saccades. As with other trinucleotide repeat disorders, SCA2 exhibits an inverse correlation between the size of the CAG repeat and the age at onset of clinically detectable disease, with neonatal cases of SCA2 being reported in individuals harboring over 200 CAG repeats. However, a wide range of age at onset is typically observed, especially in individuals with < 40 CAG repeats. CAG repeat number alone explains approximately 25-80% of the variability. In this paper, we hypothesize that the level of mutant ataxin-2 protein in affected cells contributes to these differences. One of the mechanisms that might influence this protein levels is de novo DNA methylation, which would specifically target the allele with the expanded CAG repeat leading to transcriptional silencing. Consequently, the symptoms of SCA2 would occur later in the patient's life history. Our postulations, as well as those previously reported to account for the phenotype of SCA2, are discussed.

Identification of human male meiotic chromosomes.

The study is based on examinations of surgical testicular biopsies performed in eleven men aged from 19-79 years (300 cells at leptotent stage, 19 at zygotene, 300 cells at pachytene, 490 spermatocytes at diakinesis/first metaphase and 23 cells at the second metaphase of meiotic division), as well as post-mortem necropsies taken from six men aged from 19-51 years (6,000 cells at the first meiotic prophage). Identification of chromosomes at leptotene and zygotene stages is limited to the determination of X and Y chromosomes enclosed in the sex vesicle. At the pachytene stage, identification of chromosomes can make use of the differences in their length and number of chromomeres, but is feasible only in figures with good chromosome spreading. Identification of chromosomes at diakinesis/first metaphase in preparations stained by classical methods rests on the size and shape of the bivalents. Application of centromeric heterochromatin staining technique enables us to differentiate among bivalents Nos. 1, 2, and 3, to recognize bivalents belonging to the B group, to identify bivalents Nos. 9, 16, 17-18, and to distinguish between bivalent No. 21 and 22. It further permits the modality of pairing of the X and Y chromosomes to be determined by their short arms. Chromosomes of secondary spermatocytes at metaphase show typical morphological characteristics essential for karyotyping, so that it is possible to arrange them into the haploid karyotype, analogous to the karyotype of somatic cells. Male germinal cells undergo very rapid autolytic changes. No spermatocytes at diakinesis/first metaphase stage could be detected in specimens taken as early as 2 hours after death. The morphology of chromosomes of cells at earlier stages of the first meiotic prophase was markedly altered. Post-mortem testicular material was found unsuitable for an analysis of meiotic chromosomes.