Atom-scale compositional distribution in InAlAsSb-based triple junction solar cells by atom probe tomography.

The analysis by atom probe tomography (APT) of InAlAsSb layers with applications in triple junction solar cells (TJSCs) has shown the existence of In- and Sb-rich regions in the material. The composition variation found is not evident from the direct observation of the 3D atomic distribution and because of this a statistical analysis has been required. From previous analysis of these samples, it is shown that the small compositional fluctuations determined have a strong effect on the optical properties of the material and ultimately on the performance of TJSCs.

Atom probe tomography quantification of carbon in silicon.

Atom Probe Tomography (APT) was used to quantify carbon in implanted silicon at two various electric fields (~ 15 and 20 V/nm). Using equal proportions of implanted 12C and 13C, the numerous molecular ions that were observed were identified and their contribution to the carbon content statistically derived. Much more accurate carbon quantification was obtained in the lowest electric field analysis by comparing APT with Secondary Ion Mass Spectroscopy profiles. This was assigned to a lower amount of molecular ion dissociations. Furthermore, the number of self-interstitials trapped per carbon atom in clusters was derived. This value of interest for the microelectronics industry regarding dopant diffusion and implantation induced defects was estimated close to one, in agreement with the expected stoichiometry of the SiC phase present in the phase diagram. However, this was obtained only when using low electric field conditions.

Clustering and nearest neighbour distances in atom probe tomography: the influence of the interfaces.

The statistical 1NN method is an elegant way to derive the composition of small B-enriched clusters in a random AB solid solution from 3D atomic fields. An extension of this method is proposed that includes the contribution of interface region and provides an estimate of the core composition of clusters. This model is applied to boron-implanted silicon containing boron-enriched clusters. A comparison with the previous model is performed. This new approach gives relevant information, i.e. the core composition of clusters and the cluster-matrix interface width.

Haemophilus influenzae and Streptococcus pneumoniae infections in children with cerebrospinal fluid shunts.

OBJECTIVE: This paper reviews the frequency of central nervous system infections due to Haemophilus influenzae and Streptococcus pneumoniae associated with cerebrospinal fluid (CSF) shunts in pediatric patients. The need for immunizations in this patient population is also evaluated. PATIENTS: All patients with cerebrospinal fluid shunts except those with brain tumors seen in our clinics. METHODS: We reviewed data in three computer databases, kept prospectively recording details of CSF shunt procedures and CSF shunt-related infections. RESULTS: 1,226 patients underwent 3,889 shunt placements between 1957 and 2007. Twelve patients had 14 episodes of Haemophilus or pneumococcal infections. CONCLUSIONS: Children with CSF shunts are at high risk for infection with H. influenzae and S. pneumoniae. Routine immunizations during infancy in addition to the 23-valent polysaccharide pneumococcal vaccine should be highly and actively encouraged by health care providers caring for children with CSF shunts. Additional expanded-coverage vaccines should be utilized if and when they become available.

Nucleotide sequence and tissue distribution of three insulin-like growth factor I prohormones in salmon.

Tissue distribution and potential alternative splicing of insulin-like growth factor I (IGF-I) messenger RNA were studied using reverse transcriptase-polymerase chain reaction (RT-PCR) on RNA from several tissues at various stages of the life cycle of coho salmon (Oncorhynchus kisutch). DNA sequence analysis of RT-PCR products revealed three IGF-I mRNA transcripts, designated Ea-1, Ea-2, and Ea-3, which code for three distinct prohormones, IGF-IA-1, IGF-IA-2, and IGF-IA-3, respectively. The E-domain of proIGF-IA-1 is 35 amino acids long and shares 77% sequence identity with the E-domain of human proIGF-IA, which is also 35 amino acids long. The proIGF-IA-2 and proIGF-IA-3 E-domains are homologous to the proIGF-IA-1 E-domain but contain 27 and 39 amino acid inserts, respectively, between Lys86 and Glu87. In the human IGF-I gene Lys86 is coded by exon 4 and Glu87 is coded by exon 6. This suggests that Ea-2 and Ea-3 transcripts may be the result of alternative splicing during pre-mRNA processing. All three transcripts were readily detectable using a solution hybridization/RNase protection assay. Furthermore, RT-PCR and DNA sequencing analysis indicate the presence of three IGF-I prohormones in another member of the Salmonidae family, the Atlantic salmon (Salmo salar). An analysis of IGF-I and -II E-domains from several vertebrates suggests that certain chemical and physical properties of the molecule are well conserved despite wide variations in primary structure. Ea-1, Ea-2, and Ea-3 transcripts were found in whole embryos, and liver, muscle, and brain of juvenile and adult salmon. At least one IGF-I transcript was found in heart, kidney, testes, ovary, adipose tissue, and spleen of juvenile salmon. These results indicate that IGF-I is expressed during embryonic development of fish, and that most tissues are capable of IGF-I mRNA production. These data also indicate that pre-mRNA transcripts can be alternatively spliced to yield at least three prohormones.

Nucleotide sequence and growth hormone-regulated expression of salmon insulin-like growth factor I mRNA.

Protein and cDNA sequence analysis have revealed that the insulin-like growth factor (IGF-I) has been highly conserved among several mammalian species. Using the combined techniques of polymerase chain reaction and molecular cloning, we have now obtained the cDNA sequence encoding preproIGF-I from a teleost species, Oncorhynchus kisutch (coho salmon). The 2020 nucleotide (nt) cloned cDNA sequence contains a 528 nt open reading frame encoding 176 amino acids in preproIGF-I and 175 nt and 1317 nt of flanking 5'- and 3'-untranslated regions, respectively. The deduced amino acid sequence of salmon IGF-I is highly conserved relative to its mammalian homologues and there are only 14 amino acid differences out of 70 between salmon and human IGF-I. Interestingly, the C-terminal E domain of salmon proIGF-I, which is presumed to be proteolytically cleaved during biosynthesis, also shows striking amino acid sequence homology with its mammalian counterpart, except for an internal 27 residue segment that is unique to salmon proIGF-I. Northern analysis revealed that salmon preproIGF-I mRNA consists predominantly of a single 3900 nt sized band although minor bands were also observed after prolonged autoradiographic exposure. The RNA analysis also revealed that the level of preproIGF-I mRNA is increased 6-fold in liver RNA isolated from salmon injected with bovine GH, as compared to untreated controls. These results demonstrate that the primary structure and regulated expression of IGF-I by GH have been conserved in teleosts.

An analytical model accounting for tip shape evolution during atom probe analysis of heterogeneous materials.

An analytical model describing the field evaporation dynamics of a tip made of a thin layer deposited on a substrate is presented in this paper. The difference in evaporation field between the materials is taken into account in this approach in which the tip shape is modeled at a mesoscopic scale. It was found that the non-existence of sharp edge on the surface is a sufficient condition to derive the morphological evolution during successive evaporation of the layers. This modeling gives an instantaneous and smooth analytical representation of the surface that shows good agreement with finite difference simulations results, and a specific regime of evaporation was highlighted when the substrate is a low evaporation field phase. In addition, the model makes it possible to calculate theoretically the tip analyzed volume, potentially opening up new horizons for atom probe tomographic reconstruction.

Conservation of PDX-1 structure, function, and expression in zebrafish.

Development of the mammalian pancreas has been studied extensively in mice. The stages from budding of the pancreatic anlaga through endocrine and exocrine cell differentiation and islet formation have been described in detail. Recently, the homeodomain transcription factor PDX-1 has been identified as an important factor in the proliferation and differentiation of the pancreatic buds to form a mature pancreas. To evaluate the possibility of using zebrafish as a model for the genetic analysis of pancreas development, we have cloned and characterized PDX-1 from this organism. The deduced sequence of zebrafish PDX-1 contains 246 amino acids and is 95% identical to mammalian PDX-1 in the homeodomain. We also cloned zebrafish preproinsulin complementary DNA as a marker for islet tissue. By in situ hybridization we demonstrate that PDX-1 and insulin are coexpressed during embryonic development and in adults, although PDX-1 expression appears to be biphasic. Insulin expression apparently begins before 44 hpf, the earliest stage examined in this study. Additionally, very high levels of PDX-1 expression were observed in the pyloric caeca, the accessory digestive organs that also are derived from the proximal region of the intestine in teleosts. Finally, our data show that the evolutionary conservation of zebrafish PDX-1 extends to its DNA binding properties. Zebrafish PDX-1 was equally as effective as mouse PDX-1 in stimulating insulin gene transcription, and maximum promoter activation was dependent on the presence of four intact A elements. The demonstration of this capability suggests that transcriptional regulatory mechanisms that control pancreatic development and insulin gene expression have been conserved among vertebrates.

Divergence of insulin-like growth factors I and II in the elasmobranch, Squalus acanthias.

Recent studies have shown that vertebrates, including teleostean fishes, amphibians, birds and mammals, contain two distinct insulin-like growth factor (IGF) genes. In contrast agnathans, represented by hagfish, apparently have only one IGF that has features characteristic of both IGF-I and IGF-II. Between these groups the elasmobranchs occupy a critical position in terms of the phylogeny of IGFs. We sought to determine if gene duplication and divergence of IGF-I and IGF-II occurred before or after divergence of elasmobranchs from other vertebrates by cloning IGF-like molecules from Squalus acanthias. Our analysis shows that Squalus liver produces two distinct IGF-like molecules. One has greater sequence identity to, and conserved features characteristic of, known IGF-I molecules, while the other is more IGF-II like. These results suggest that the prototypical IGF molecule duplicated and diverged in an ancestor of the extant gnathostomes.

Differential expression and hormonal regulation of alternatively spliced IGF-I mRNA transcripts in salmon.

Salmon have been shown to express alternatively spliced IGF-I mRNA transcripts coding for four different IGF-I prohormones. These transcripts, now designated Ea-1, Ea-2, Ea-3 and Ea-4, differ in size due to the inclusion of additional sequences in the E domain-coding region of the molecule. In this study, the tissue distribution and hormonal regulation of expression of alternatively spliced IGF-I mRNA transcripts were investigated in coho salmon. IGF-I mRNAs were detected by solution hybridization/RNase protection assay in all tissues examined. GH treatment significantly increased hepatic IGF-I mRNA content. Hepatic IGF-I mRNA levels were not influenced by prolactin or somatolactin. Heart, fat, brain, kidney, spleen and ovary IGF-I mRNA levels were not affected by GH, prolactin or somatolactin. Ea-1, Ea-3 and Ea-4 mRNA transcripts were detectable in the liver, and Ea-1 and Ea-3 levels increased dramatically in response to GH treatment, whereas the amount of Ea-4 mRNA was unchanged. Most non-hepatic tissues expressed only the Ea-4 transcript, and expression was not influenced by GH, prolactin or somatolactin. Ea-1 and Ea-3 transcripts were visible in gill samples from fish treated with GH. The ovaries of juvenile fish expressed Ea-1, Ea-2 and Ea-4. The amounts of these transcripts were not changed by gonadotrophin treatment. During smoltification of juvenile coho salmon, liver and gill IGF-I mRNA levels increased with increasing plasma GH and thyroxine concentrations. Muscle, brain and ovary IGF-I mRNA levels were unchanged during this period. These data suggest that the liver is a major site of IGF-I production in response to GH. Heart, fat, brain, kidney, spleen and ovary did not show increased IGF-I mRNA levels in response to GH treatment. GH and prolactin had inconsistent effects on muscle IGF-I mRNA levels. Somatolactin and a gonadotrophin preparation did not stimulate IGF-I expression in tissues of juvenile fish. Differences in tissue GH responsiveness can be partially explained by the expression of alternatively spliced IGF-I mRNAs. Of the four hepatic IGF-I mRNA transcripts, Ea-1 and Ea-3 are GH-responsive, while Ea-2 and Ea-4 are not. Most non-hepatic tissues express only the Ea-4 transcript, and IGF-I mRNA levels do not increase after GH treatment. The increased IGF-I mRNA levels observed in gill tissue during smoltification suggest that other factors, in addition to GH, may regulate IGF-I expression.(ABSTRACT TRUNCATED AT 400 WORDS)

Developmental and tissue-regulated expression of IGF-I and IGF-II mRNAs in Sparus aurata.

Recent studies have shown that homologues of the mammalian IGF-I and -II genes are also found in teleosts. We report here the cDNAs coding for IGF-I and IGF-II cloned from the gilthead seabream, Sparus aura ta. Sequence comparisons revealed that both IGFs have been well conserved among teleosts, although Sparus IGF-I is shorter bv three amino acid residues due to truncated B-and C-domains. Using the cloned cDNAs as probes, the relative expression of IGF-I and IGF-II mRNAs were assayed in different Sparus tissues. Sparus liver clearly contained the highest level of IGF-I mRNA while relatively high levels of IGF-II mRNA were found in liver, heart and gill using the ribonuclease protection assay. After GH administration the amount of IGF-I mRNA was increased by 220% in liver but no changes in IGF-II mRNA levels were detected in any tissue. We also assayed the expression of IGF-I and IGF-II in Sparus during early development. The IGF-II mRNA level was highest in larva I day after hatching and decreased thereafter. In contrast, IGF-I mRNA was detected in 1-day-old larva but there was an increase in expression in 12- and 16-day-old larva. These results demonstrated that the expression of IGF-I and IGF-II is highly regulated in teleosts and suggest that they play distinct roles during growth and development.

Characterization of a salmon insulin-like growth factor I promoter.

We have identified four transcription initiation sites in the salmon insulin-like growth factor I (IGF-I) gene. Use of the most upstream transcription start site generates a minor mRNA species with a 5' untranslated region (UTR) of approximately 450-550 nucleotides, whereas transcription starting at the downstream initiation sites results in more abundant IGF-I mRNAs with 5'-UTRs approximately 250, 245, and 165 nucleotides in length. No consensus TATA box-like elements are present immediately upstream of the most upstream start site identified, nor is this region particularly GC-rich. Transient expression assays, however, demonstrated orientation-dependent promoter activity in a 386-nucleotide-long fragment containing the major downstream transcription start sites. Additionally, reverse transcriptase polymerase chain reaction (RT-PCR) analyses demonstrated tissue and developmental stage-specific use of the various transcription start sites identified.

Longevity of patients born with myelomeningocele.

There are limited data concerning the life expectancy for individuals born with myelomeningocele (MM), with and without hydrocephalus. To ascertain such data was our first purpose. We have selected all patients with MM in our computer database, The Patient Data Management System (PDMS/fx). Data were transferred to Excel for primary and SPSS/PC for final analysis by Kaplan-Meier life survival curves. Of the 1,054 patients with MM in the Birth Defects Clinic and the University of Washington Medical Center (UWMC) of Seattle, 505 are now over the age of 21 (391) or have died (114). Follow-up information was available since 1994 for 132, 62% of whom we have had contact within the past 2 years. The second purpose was to identify potential health factors associated with long-term outcome of patients with MM. Patient variables chosen as relevant to survival included hydrocephalus, treatment before or after 1975, and health maintenance determined by outcome for those receiving care within the last 5 years or those last seen before. Age at last appointment and reason for visit were determined in order to identify age-specific health care needs of the adult population. Survival and medical needs were obtained from the UWMC's computer database, Mindscape, and by telephone survey for adult patients not seen in the last 2 years. Death is more frequent earlier in life for those MM patients with hydrocephalus. Ordinary degenerative disorders affect MM patients earlier in life than normals. Our data extend life expectancy for patients with MM and hydrocephalus to age 40 years with some reliability for those treated from 1957 to 1974, but only 24 years for those treated with modern techniques after 1974. More data is needed to determine long-term survival.

Epidemiology of tethered cord with meningomyelocele.

This paper describes the epidemiology of tethered cord syndrome and its etiologies and co-morbidities following initial repair of both meningomyeloceles and lipomeningomyelocele. A review of the pertinent literature and data from 654 cases of meningomyelocele and 118 cases of lipomeningomyelocele has been drawn from a computerized database, Patient Data Management System/fx. Only cases born since 1964 were analyzed for the etiologies, co-morbidities, spinal cord abnormalities detected by contrast studies or MRI and for significant symptoms and signs. Tethered cord symptoms were related to an attachment to a rigid tether for all 31 cases following lipomeningomyelocele repair but 62 (75%) of the 83 post meningomyelocele repair patients developed the symptoms of tethered cord. Causes other than, or in addition to, tethering included an obstructed cerebrospinal fluid shunt, syringohydromyelia, benign tumor and spinal cord hypoplasia. Quantitative differentiation between asymptomatic thin spinal cords and symptomatic spinal cord hypoplasia as well as between central canal enlargement and symptomatic syringohydromyelia could not be demonstrated. Collaborative, multi-center studies of larger numbers of patients are recommended.

3D analysis of advanced nano-devices using electron and atom probe tomography.

The structural and chemical properties of advanced nano-devices with a three-dimensional (3D) architecture have been studied at the nanometre scale. An original method has been used to characterize gate-all-around and tri-gate silicon nanowire transistor by combining electron tomography and atom probe tomography (APT). Results show that electron tomography is a well suited method to determine the morphological structure and the dimension variations of devices provided that the atomic number contrast is sufficient but without an absolute chemical identification. APT can map the 3D chemical distribution of the atoms in devices but suffers from strong distortions in the dimensions of the reconstructed volume. These may be corrected using a simple method based on atomic density correction and electron tomography data. Moreover, this combination is particularly useful in helping to understand the evaporation mechanisms and improve APT reconstructions. This paper demonstrated that a full 3D characterization of nano-devices requires the combination of both tomography techniques.

Point process statistics in atom probe tomography.

We present a review of spatial point processes as statistical models that we have designed for the analysis and treatment of atom probe tomography (APT) data. As a major advantage, these methods do not require sampling. The mean distance to nearest neighbour is an attractive approach to exhibit a non-random atomic distribution. A χ(2) test based on distance distributions to nearest neighbour has been developed to detect deviation from randomness. Best-fit methods based on first nearest neighbour distance (1 NN method) and pair correlation function are presented and compared to assess the chemical composition of tiny clusters. Delaunay tessellation for cluster selection has been also illustrated. These statistical tools have been applied to APT experiments on microelectronics materials.

Advance in multi-hit detection and quantization in atom probe tomography.

The preferential retention of high evaporation field chemical species at the sample surface in atom-probe tomography (e.g., boron in silicon or in metallic alloys) leads to correlated field evaporation and pronounced pile-up effects on the detector. The latter severely affects the reliability of concentration measurements of current 3D atom probes leading to an under-estimation of the concentrations of the high-field species. The multi-hit capabilities of the position-sensitive time-resolved detector is shown to play a key role. An innovative method based on Fourier space signal processing of signals supplied by an advance delay-line position-sensitive detector is shown to drastically improve the time resolving power of the detector and consequently its capability to detect multiple events. Results show that up to 30 ions on the same evaporation pulse can be detected and properly positioned. The major impact of this new method on the quantization of chemical composition in materials, particularly in highly-doped Si(B) samples is highlighted.

Clustering and pair correlation function in atom probe tomography.

The measurement of the composition of small clusters from 3D maps as provided by atom probe tomography or Monte-Carlo simulations is a very tricky issue. A method based on pair correlation functions was developed. The analytical expression of the pair correlation function as a function of the phase composition, the number density and the size of spherical particles for a two-phase mono-dispersed system has been established. A best-fit procedure applied to experimental pair correlation function is shown to be a simple, fast and elegant way to determine the concentration of clusters and that of the parent phase as well as the radius and the number density of clusters. Application to carbon-doped silicon demonstrates the validity of this approach. Results were found very close to those derived by other means. This method was also applied to boron clustering in implanted silicon where clusters are not visible in 3D images. The advantage of this approach over other methods such as erosion or cluster identification is discussed.

Clustering and nearest neighbour distances in atom-probe tomography.

The measurement of chemical composition of tiny clusters is a tricky problem in both atom-probe tomography experiments and atomic simulations. A new approach relying on the distribution of the first nearest neighbour (1NN) distances between solute atoms in the 3D space composed of A and B atoms was developed. This new approach, the 1NN method, is shown to be an elegant way to get the composition of tiny B-enriched clusters embedded in a random AB solid solution. The theoretical statistical distributions of first neighbour distances P(r) for both random solid solution and solute-enriched clusters finely dispersed in a depleted matrix are established. It is shown that the most probable distance of P(r) gives directly the phase composition. Applications of this model to both one-phase SiGe alloy and boron-doped silicon containing small clusters indicate that this new approach is quite reliable.

Insulin-like growth factor I (IGF-I) mRNA expression in coho salmon, Oncorhynchus kisutch: Tissue distribution and effects of growth hormone/prolactin family proteins.

To examine the hormonal and nutritional regulation of insulin-like growth factor I (IGF-I) mRNA expression, a sequence-specific solution hybridization/RNase protection assay for coho salmon IGF-I mRNA was developed. This assay is both rapid and sensitive and has low inter- (less than 15%) and intra-assay variations (less than 5%). Using this assay, the tissue distribution of IGF-I mRNA and effects of growth hormone (GH), prolactin (PRL) and somatolactin (SL) on hepatic IGF-I mRNA expression in coho salmon were examined in vivo. Liver had the highest IGF-I mRNA level of 16 pg/µg DNA. Significant amounts of IGF-I mRNA were also found in all other tissues examined (intestine 4.1, kidney 3.8, gill arch 2.4, brain 2.4, ovary 2.3, muscle 2.1, spleen 1.7 and fat 1.1 pg/µg DNA). Injection of coho salmon GH at doses of 0.1 and 1 µg/g body weight significantly increased the hepatic IGF-I mRNA levels in a dose-dependent manner. Injection of coho salmon SL, a recently discovered member of the GH/PRL family, stimulated the IGF-I mRNA expression at the higher dose (1 µg/g), whereas coho salmon PRL had no effect at either dose. Concentration-dependent stimulation by coho salmon GH was also obtained in vitro in primary culture of salmon hepatocytes in concentrations ranging from 0.01 to 1 µg/ml. These results indicate that IGF-I mRNA expression occurs in a variety of tissues in coho salmon, and that at least the hepatic expression is under the regulation of GH and possibly other hormones. The sequence-specific assay established in the present study can be used for accurate quantitation of IGF-I mRNA in salmonid species, and can contribute to a better understanding of the physiology of IGF-I in salmonids.