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Strain sensing around the fastener holes is fundamentally significant in structural health monitoring and failure detections. Conventional non-destructive testing (NDT) techniques typically have limitations in performing reliable and efficient inspections. Here, a laser speckle imaging system (LSIS) has been developed to achieve non-contact, non-destructive and remote strain sensing. Methods for determining optimal laser speckle patterns have been investigated to achieve remote sensing of strain up to a working distance of 5 m. This LSIS was applied to study the anisotropic properties of un-notched and circular notched specimens in cold-rolled aluminium sheet, an important material for the construction of lightweight aircraft structures. The results showed that strain distributions determined by LSIS are consistent with finite element (FE) predictions in which the evolution of strain concentrations not only depends on the notch size but also on material anisotropy. This study demonstrates the potential application of LSIS as an effective NDT technique for full-field, non-contact and remote sensing of anisotropic deformation around fastener holes.

Addressing the increase in complexity and number of orthopaedic surgeries especially in the aging population is a major challenge to orthopaedic surgeons. The availability of physical model of patient-specific bones can benefit pre-operative planning of surgeries and lead to better surgical options and improved outcomes. This paper describes a CT-based agile 3D printing system for manufacturing patient-specific bones that can be used for preoperative planning and assist in the choice and application of orthopaedic implants.

Mutations and deletions in PTEN-induced kinase 1 (PINK1) cause autosomal recessive Parkinson's disease (PD), the second most common neurodegenerative disorder. PINK1 is a nuclear-genome encoded Ser/Thr kinase in mitochondria. PINK1 deletion was reported to affect dopamine (DA) levels in the striatum and mitochondrial functions but with conflicting results. The role of PINK1 in mitochondrial function and in PD pathogenesis remains to be elucidated thoroughly. In this study, we measured DA release using fast-scan cyclic voltammetry in acute striatal slices from both PINK1 knockout (KO) and wild-type (WT) mice at different ages. We found that single pulse-evoked DA release in the dorsal striatum of PINK1 KO mice was decreased in an age-dependent manner. Furthermore, the decrease was because of less DA release instead of an alteration of DA transporter function or DA terminal degeneration. We also found that PINK1 KO striatal slices had significantly lower basal mitochondria respiration compared with that of WT controls, and this impairment was also age-dependent. These results suggest that the impaired DA release is most likely because of mitochondrial dysfunction and lower ATP production.

This paper presents a Slope one improved algorithm based on user similarity and user interest forgetting function. Aiming at the problem of large number of users and a lot of noise data, the inactive users are filtered out by setting the threshold of user activity, and then the neighbors of the target users are obtained through the calculation of user similarity. According to interest forgetting function, and then filter out items that have less effect on current users to reduce the noise data to improve the accuracy of the algorithm. Experimental comparison shows that the improved algorithm has better accuracy than the commonly used weighted Slope one and two-pole Slope one.

In the modern supply chain management, optimizing supply chain can reduce the cost of the enterprise. In the optimization of supply chain, the inventory optimization is a very important part. Through forecasting the inventory amount, we can reduce the cost of the inventory. And we also can optimize the supply chain. Because the supply chain network is complex, we use the chaos theory to study and predict the inventory. In this paper, we put forward a chaotic forecasting method which is based on the BP neural and genetic algorithm. This new method is BP-GA chaos prediction algorithm. We use the method to predict the inventory amount. The experiment shows that the method has achieved good forecasting effect.

The homogenized hoop elastic moduli are key parameters of RTPs that must be considered in the buckling collapse predictions and pipe designs. However, it is difficult to give an accurate analytical solution due to the material anisotropy of RTPs. To address this problem, a novel method is proposed based on the classical elastic stability theory and NASA SP-8007 formula. This method is under the assumption that the critical pressures of homogenized RTPs equal the critical pressures calculated by the classical lamination theory and Donnell-type stability differential equations. One advantage of this method is that it could simultaneously consider the extensional response, the bending response, and the extensional-bending coupling response of laminates in the calculation of homogenized hoop elastic moduli. Meanwhile, it gives a more concise formula form and doesn’t involve successive iterations in comparison with the existing homogenization method. Numerical simulations of the crushing case were used to verify the effectiveness of the proposed method. Compared with numerical results and the existing homogenization method, the proposed method was found to give accurate results. Furthermore, the effects of fiber’s winding angles and thickness-radius ratios, and the proportional relations between the homogenized hoop elastic moduli and the reciprocal of radii were investigated.

Reinforced thermoplastic pipes (RTPs) can experience collapse under external pressure. The maximum external pressure that RTPs can resist before buckling collapse must be considered in engineering practice. To predict the critical pressure of RTPs, a new analytical model is proposed by analyzing the hoop stress distributions of crushed rings. The model is made under the assumption that the maximum hoop stress equals the critical stress when pipes collapse. Different from the previously reported studies, focusing on axial compression, the critical stress of cylinders' buckling under crushing loads is formulated. With regard to the material anisotropy of RTPs, the equivalent stiffness method is applied to obtain the homogenized hoop elastic modulus in the proposed model. The effectiveness of the proposed model is verified by eigenvalue analyses on solid models and continuum shell models. Compared with numerical methods and Timoshenko and Gere (1961), the proposed model was found to give accurate critical pressures and hoop stress distributions. Furthermore, the optimal range for fiber’s winding angle is obtained, and the effect of thickness-radius ratios on critical pressure and the disproportionate motions of singularity points are also discussed.

Passive immunization with anti-tau monoclonal antibodies has been shown by several laboratories to reduce age-dependent tau pathology and neurodegeneration in mutant tau transgenic mice. These studies have used repeated high weekly doses of various tau antibodies administered systemically for several months and have reported reduced tau pathology of ∼40–50% in various brain regions. Here we show that direct intrahippocampal administration of the adeno-associated virus (AAV)-vectored anti-phospho-tau antibody PHF1 to P301S tau transgenic mice results in high and durable antibody expression, primarily in neurons. Hippocampal antibody levels achieved after AAV delivery were ∼50-fold more than those reported following repeated systemic administration. In contrast to systemic passive immunization, we observed markedly reduced (≥80–90%) hippocampal insoluble pathological tau species and neurofibrillary tangles following a single dose of AAV-vectored PHF1 compared with mice treated with an AAV-IgG control vector. Moreover, the hippocampal atrophy observed in untreated P301S mice was fully rescued by treatment with the AAV-vectored PHF1 antibody. Vectored passive immunotherapy with an anti-tau monoclonal antibody may represent a viable therapeutic strategy for treating or preventing such tauopathies as frontotemporal dementia, progressive supranuclear palsy, or Alzheimer's disease.SIGNIFICANCE STATEMENTWe have used an adeno-associated viral (AAV) vector to deliver the genes encoding an anti-phospho-tau monoclonal antibody, PHF1, directly to the brain of mice that develop neurodegeneration due to a tau mutation that causes frontotemporal dementia (FTD). When administered systemically, PHF1 has been shown to modestly reduce tau pathology and neurodegeneration. Since such antibodies do not readily cross the blood–brain barrier, we used an AAV vector to deliver antibody directly to the hippocampus and observed much higher antibody levels and a much greater reduction in tau pathology. Using AAV vectors to deliver antibodies like PHF1 directly to brain may constitute a novel approach to treating various neurodegenerative disorders, such as FTD and Alzheimer's disease.

Drosophila genetics is one of the most powerful tools in modern biology. For many years, the "forward genetic" approach using Drosophila has been extraordinarily successful in elucidating the molecular pathways of many physiological processes and behaviors. Recently, the "reverse genetic" approach in Drosophila is increasingly being developed as a major tool for research in biology, especially in the study of human diseases. Parkinson's disease (PD) is the second most common neurodegenerative disease. Kinase signaling has been directly implicated in PD pathogenesis. Mutations in PTEN-induced kinase 1 (PINK1) cause PARK6 type PD, in which mitochondrial deficits are at the center of pathogenesis. Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most prevalent genetic cause of both familial (PARK8 type with autosomal dominant inheritance) and sporadic PD. To understand the mechanism of PINK1- and LRRK2- mediated pathogenesis, reverse-engineered Drosophila models have been critical tools. Here the authors will discuss the usage of Drosophila models in their and other laboratories, and share scientific insights that originate from these studies, and discuss their experimental results of the effect of PINK1 on proteasome function. The authors will also comment on the different approaches taken in these lines of investigation.

Mutations in PTEN-induced kinase 1 (PINK1), a mitochondrial Ser/Thr kinase, cause an autosomal recessive form of Parkinson's disease (PD), PARK6. To investigate the mechanism of PINK1 pathogenesis, we used the Drosophila Pink1 knockout (KO) model. In mitochondria isolated from Pink1-KO flies, mitochondrial respiration driven by the electron transport chain (ETC) is significantly reduced. This reduction is the result of a decrease in ETC complex I and IV enzymatic activity. As a consequence, Pink1-KO flies also display a reduced mitochondrial ATP synthesis. Because mitochondrial dynamics is important for mitochondrial function and Pink1-KO flies have defects in mitochondrial fission, we explored whether fission machinery deficits underlie the bioenergetic defect in Pink1-KO flies. We found that the bioenergetic defects in the Pink1-KO can be ameliorated by expression of Drp1 , a key molecule in mitochondrial fission. Further investigation of the ETC complex integrity in wild type, Pink1-KO, PInk1-KO/Drp1 transgenic, or Drp1 transgenic flies indicates that the reduced ETC complex activity is likely derived from a defect in the ETC complex assembly, which can be partially rescued by increasing mitochondrial fission. Taken together, these results suggest a unique pathogenic mechanism of PINK1 PD: The loss of PINK1 impairs mitochondrial fission, which causes defective assembly of the ETC complexes, leading to abnormal bioenergetics.

A heterostructural composite composed of g-C3N4 and Bi2O3 was achieved by the one-pot and thermal-induced polycondensation method using melamine and Bi(NO[Formula: see text] as precursor at 550[Formula: see text]C under air atmosphere. The crystalline phase, components and morphologies of the as-prepared composites were investigated by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM). Besides, the photocatalytic activity of composites was evaluated by degrading RhB aqueous solution at room temperature under visible light irradiation. Compared with bulk g-C3N4, the photocatalytic efficiency of the 0.5% Bi2O3/g-C3N4 (Bi–CN) was increased by up to four times. The introduction of Bi2O3 enhances not only the light absorption ability, but also the separation of photogenerated electron–hole pairs.

Microglia have been shown to contribute to the clearance of brain amyloid β peptides (Aβ), the major component of amyloid plaques, in Alzheimer’s disease (AD). However, it is not known whether microglia play a similar role in the clearance of tau, the major component of neurofibrillary tangles (NFTs). We now report that murine microglia rapidly internalize and degrade hyperphosphorylated pathological tau isolated from AD brain tissue in a time-dependent manner in vitro. We further demonstrate that microglia readily degrade human tau species released from AD brain sections and eliminate NFTs from brain sections of P301S tauopathy mice. The anti-tau monoclonal antibody MC1 enhances microglia-mediated tau degradation in an Fc-dependent manner. Our data identify a potential role for microglia in the degradation and clearance of pathological tau species in brain and provide a mechanism explaining the potential therapeutic actions of passively administered anti-tau monoclonal antibodies.

Anti-tau immunotherapy has been proposed as a promising therapy for various tauopathies including Alzheimer's disease (AD), frontotemporal dementia (FTD) and progressive supranuclear palsy (PSP). However, there are limitations to passive immunization including the need for repeated administration and the very low levels of antibody that get into brain from the circulation. To circumvent the disadvantages of passive immunization, we have used serotype rh. 10 adeno-associated virus vectors to deliver an anti-tau monoclonal antibody PHF1, known to reduce tau pathology following passive immunization in several tauopathy mouse models directly to the CNS. To accomplish this, we stereotactically administered 1010 viral genomes (vg) of AAVrh. 10-PHF1 or AAVrh. 10-mCherry as a control, bilaterally into the hippocampus of young (3.5-month old) homozygous P301L mice, a model that develops robust tau pathology in an age- and brain region-dependent manner. Six months after injection, mice were sacrificed to measure the presence of anti-tau antibody as well as the effects of treatment on tau pathology in several brain regions using specific ELISAs and immunohistochemistry (IHC) for quantifying pathological and normal tau. In pilot experiments using wild-type C57BL/6 and P301L mice, we observed much higher levels of PHF1 antibody in the hippocampus when delivered via the AAVrh. 10 vector compared to passive immunization (3100-fold higher). We observed that treatment with AAVrh. 10-PHF1 resulted in a marked antibody-dependent reduction in tau pathology in P301L mice, including a highly significant reduction in tau pathology in the hippocampus (≥80-90% p=0.001) compared to the control vector. There was also no reduction in total tau measured by ELISA in any brain region examined. Based on these observations, AAVrh. 10 gene delivery of anti-tau monoclonal antibodies to the CNS may represent a novel therapeutic strategy for treating various tauopathies including FTD, PSP and AD.

Huntington's disease (HD) is caused by expansion of a polyglutamine tract near the N-terminal of huntingtin. Mutant huntingtin forms aggregates in striatum and cortex, where extensive cell death occurs. We used a Drosophila polyglutamine peptide model to assess the role of specific cell death regulators in polyglutamine-induced cell death. Here, we report that polyglutamine-induced cell death was dramatically suppressed in flies lacking Dark, the fly homolog of human Apaf-1, a key regulator of apoptosis. Dark appeared to play a role in the accumulation of polyglutamine-containing aggregates. Suppression of cell death, caspase activation and aggregate formation were also observed when mutant huntingtin exon 1 was expressed in homozygous dark mutant animals. Expanded polyglutamine induced a marked increase in expression of Dark, and Dark was observed to colocalize with ubiquitinated protein aggregates. Apaf-1 also was found to colocalize with huntingtin-containing aggregates in a murine model and HD brain, suggesting a common role for Dark/Apaf-1 in polyglutamine pathogenesis in invertebrates, mice and man. These findings suggest that limiting Apaf-1 activity may alleviate both pathological protein aggregation and neuronal cell death in HD.

We conducted blinded psychiatric assessments of 26 Amish subjects (52 ± 11 years) from four families with prevalent bipolar spectrum disorder, identified 10 potentially pathogenic alleles by exome sequencing, tested association of these alleles with clinical diagnoses in the larger Amish Study of Major Affective Disorder (ASMAD) cohort, and studied mutant potassium channels in neurons. Fourteen of 26 Amish had bipolar spectrum disorder. The only candidate allele shared among them was rs78247304, a non-synonymous variant of KCNH7 (c.1181G>A, p.Arg394His). KCNH7 c.1181G>A and nine other potentially pathogenic variants were subsequently tested within the ASMAD cohort, which consisted of 340 subjects grouped into controls subjects and affected subjects from overlapping clinical categories (bipolar 1 disorder, bipolar spectrum disorder and any major affective disorder). KCNH7 c.1181G>A had the highest enrichment among individuals with bipolar spectrum disorder (χ2 = 7.3) and the strongest family-based association with bipolar 1 (P = 0.021), bipolar spectrum (P = 0.031) and any major affective disorder (P = 0.016). In vitro, the p.Arg394His substitution allowed normal expression, trafficking, assembly and localization of HERG3/Kv11.3 channels, but altered the steady-state voltage dependence and kinetics of activation in neuronal cells. Although our genome-wide statistical results do not alone prove association, cumulative evidence from multiple independent sources (parallel genome-wide study cohorts, pharmacological studies of HERG-type potassium channels, electrophysiological data) implicates neuronal HERG3/Kv11.3 potassium channels in the pathophysiology of bipolar spectrum disorder. Such a finding, if corroborated by future studies, has implications for mental health services among the Amish, as well as development of drugs that specifically target HERG3/Kv11.3.

We have isolated, by interspecies hybridization, two classes of Drosophila cDNA each encoding a different guanylate cyclase (GC). One of them encodes an alpha subunit homolog of soluble GC, designated DGC alpha 1, and the other encodes a receptor-type GC, designated DrGC. The dgc alpha 1 cDNA encodes a protein of 676 amino acids and maps to 99B. In situ hybridization to adult tissue sections showed that dgc alpha 1 mRNA is found mainly in the cell bodies of the optic lobe, central brain, and thoracic ganglia. The DGC alpha 1 protein was also localized primarily to the nervous system by immunocytochemical staining, consistent with results of in situ hybridization. However, no detectable expression of this protein was found in the retina. The other class of cDNA, drgc, maps to 76C and encodes a 1525-amino acid protein displaying structural features similar to other known receptor-type guanylate cyclases. However, it has a C-terminal 430 amino acid region that has no homology to any known proteins. drgc RNA is expressed at low levels throughout development and in adult heads and bodies. In situ hybridizations to adult tissue sections showed that drgc mRNA is expressed in a wide range of tissues, including the optic lobe, central brain, thoracic ganglia, digestive tract, and the oocyte.

The complexity of channels in 3D seismic data always makes detailed interpretation challenging. Similarly, definition of sand bars and beaches is also complicated as they are only partially visible when seismic amplitude is examined. To improve the imaging of these features, current interpretation workflows use advanced color and opacity based co-rendering techniques to merge multiple attributes information. Other than to enhance these sedimentary features in 3D views with combinations of different attributes, this paper proposes to separate their reflection waveforms directly from 3D imaging data by exploiting the waveform diversity mechanism. Our separation model is set up upon the assumption that seismic data are composed of coherent events and abrupt features (correspond to sedimentary features). According to their appearance in vertical sections, we model these two kinds of seismic features as linear structures and punctate structures respectively. Two appropriate waveform dictionaries are chosen, one of which is used for the representation of the coherent events and the other for the sedimentary features. The separation process is promoted by the sparsity of both waveform components in their corresponding representing dictionaries. The capacity of the proposed method is illustrated using modeling data and real 3D seismic data with complex depositional systems.

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson's disease. We created a LRRK2 transgenic mouse model that recapitulates cardinal features of the disease: an age-dependent and levodopa-responsive slowness of movement associated with diminished dopamine release and axonal pathology of nigrostriatal dopaminergic projection. These mice provide a valid model of Parkinson's disease and are a resource for the investigation of pathogenesis and therapeutics.

Mutations in PTEN induced kinase 1 (PINK1), a mitochondrial Ser/Thr kinase, cause an autosomal recessive form of Parkinson's disease (PD), PARK6. Here, we report that PINK1 exists as a dimer in mitochondrial protein complexes that co-migrate with respiratory chain complexes in sucrose gradients. PARK6 related mutations do not affect this dimerization and its associated complexes. Using in vitro cell culture systems, we found that mutant PINK1 or PINK1 knock-down caused deficits in mitochondrial respiration and ATP synthesis. Furthermore, proteasome function is impaired with a loss of PINK1. Importantly, these deficits are accompanied by increased alpha-synclein aggregation. Our results indicate that it will be important to delineate the relationship between mitochondrial functional deficits, proteasome dysfunction and alpha-synclein aggregation.

The WEPP in China, is the longest high-pressure pipeline in the world, eastern part of whose construction has been finished at the 1st Oct. 2003. Up to now, all the pipes of trunk line have been welded and buried under ground, about 740,000 metric tons of which were made by domestic pipe mills. Before this project the capacity of domestic pipe mills is pretty low: the max. O.D. is 711mm, the max. W.T. is 10.7mm, and the highest steel grade is API X60. However, the WEPP specification is very high: X70 with about 50% acicular ferrite, O.D. 1016mm, W.T. 14.6/17.5/21.0/26.2mm, and more than 190 J CVN value under −15 . This kind of pipe has never been made before in China. However, within about 2 years, Chinese mills successfully fulfilled the development and manufacturing of X70 steel coils and plates, the technical reconstruction of old production lines and installation of the new ones, the scientific research of pipe forming and high speed welding technology and test method, and the technology development of procedure and facilities for inside flow coating and outside 3PE coating. All the above will be detailed in this paper.Copyright © 2004 by ASME

Fragile X syndrome is a common form of inherited mental retardation caused by the absence of the fragile X mental retardation protein (FMRP). It has been hypothesized that FMRP is involved in the processing and/or translation of mRNAs. Human and mouse target-mRNAs, containing purine quartets, have previously been identified. By using cDNA-SELEX (systematic evolution of ligands by exponential enrichment), we identified another class of human target-mRNAs which contain U rich sequences. This technique, in contrast to oligonucleotide-based SELEX, allows the identification of FMRP targets directly from mRNA pools. Many of the proteins encoded by the identified FMRP targets have been implicated in neuroplasticity. Steady state levels of target-mRNAs were unchanged in the brain of fragile X mice. However, levels of two target-encoded proteins, an L-type calcium channel subunit and MAP1B, were downregulated in specific brain regions suggesting a defect in the expression of target-encoded proteins in fragile X syndrome.

A deficit in the Jerky protein in mice causes recurrent seizures reminiscent of temporal lobe epilepsy. Jerky is present in mRNA particles in neurons. We show that the N-terminal 168 amino acids of Jerky are necessary and sufficient for mRNA binding. The binding domain is similar to the two tandemly arranged homeodomain-like helix-turn-helix DNA binding motifs of centromere binding protein B. The putative helix-turn-helix motifs of Jerky can also bind double-stranded DNA and represent a novel mammalian RNA/DNA binding domain. Microarray analysis identified mRNAs encoding proteins involved in ribosome assembly and cellular stress response that specifically bound to the RNA binding domain of Jerky both in vitro and in vivo. These data suggest that epileptogenesis in Jerky-deficient mice most likely involves pathways associated with ribosome biogenesis and neuronal survival and/or apoptosis.

Temporal lobe epilepsy (TLE) is a common seizure disorder, but the underlying molecular mechanisms are unknown. We reported previously that inactivation of thejerkygene in mice causes recurrent limbic seizures highly similar to TLE. Electrophysiological studies showed abnormal firing in hippocampal neurons in these mice, but it is not known how a deficiency in the Jerky protein leads to neuronal hyperexcitability. Here we show that Jerky is a brain-specific protein with a high expression level in neurons. Jerky binds mRNAs with high affinity, and it is a component of messenger ribonucleoprotein complexesin vivo. However, Jerky is not associated with ribosomes and actively translating mRNAs. These data suggest that Jerky may regulate mRNA use in neurons, and its deficiency could lead to perturbations in the regulated use of preexisting mRNAs.

X70 large diameter linepipe with helical seam SAW were developed, with 1016mm OD and 14.6mm WT. Acicular ferrite type linepipe steel is adopted for the base material, which was found having high toughness and low yield strength loss after pipe forming. The very stringent requirements for toughness, i.e. 190J/140J for average/minimum for pipe body and 120J/90J for average/minimum for weld and HAZ were meet successfully. The yield strength loss due to Bauschinger effect was found lower than 20 MPa, which benefited.Copyright © 2002 by ASME

Bipolar disorder is a common, heritable mental illness characterized by recurrent episodes of mania and depression. Despite considerable effort to elucidate the genetic underpinnings of bipolar disorder, causative genetic risk factors remain elusive. We conducted a comprehensive genomic analysis of bipolar disorder in a large Old Order Amish pedigree. Microsatellite genotypes and high-density SNP-array genotypes of 388 family members were combined with whole genome sequence data for 50 of these subjects, comprising 18 parent-child trios. This study design permitted evaluation of candidate variants within the context of haplotype structure by resolving the phase in sequenced parent-child trios and by imputation of variants into multiple unsequenced siblings. Non-parametric and parametric linkage analysis of the entire pedigree as well as on smaller clusters of families identified several nominally significant linkage peaks, each of which included dozens of predicted deleterious variants. Close inspection of exonic and regulatory variants in genes under the linkage peaks using family-based association tests revealed additional credible candidate genes for functional studies and further replication in population-based cohorts. However, despite the in-depth genomic characterization of this unique, large and multigenerational pedigree from a genetic isolate, there was no convergence of evidence implicating a particular set of risk loci or common pathways. The striking haplotype and locus heterogeneity we observed has profound implications for the design of studies of bipolar and other related disorders., Author Summary Bipolar disorder is a common, heritable mental illness characterized by recurrent episodes of mania and depression. Despite considerable efforts genetic studies have yet to reveal the precise genetic underpinnings of the disorder. In this study we have analyzed a large extended pedigree of Old Order Amish that segregates bipolar disorder. Our study design integrates both dense genotype and whole-genome sequence data. In a combined linkage and association analysis we identify five chromosomal regions with nominally significant or suggestive evidence for linkage, several of which constitute replication of earlier linkage findings for bipolar disorder in non-Amish families. Association analysis of genetic variants in each of the linkage regions yielded a number of plausible candidate genes for bipolar disorder. The striking genetic heterogeneity we observed in this genetic isolate has profound implications for the study of bipolar disorder in the general population.

Abstract The success of combined using SSAW and LSAW pipes for oil and gas pipeline in large scale is an important breakthrough of metallurgical and steel pipe manufacturing technology in China. Based on the greatly improved quality of SSAW pipe, this technology has brought up a very reliable and economic approach for pipeline Construction and a promising prospect of expanding the use of SSAW pipe. CNPC has applied this technology to construct many oil and gas pipelines both in and outside China successfully. P. 103

The neuronal ceroid lipofuscinoses (NCLs) are a genetically heterogeneous group of progressive neurodegenerative disorders characterized by the accumulation of autofluorescent lipopigment in various tissues1. Progressive epilepsy with mental retardation (EPMR, MIM 600143) was recently recognized as a new NCL subtype2 (CLN8). It is an autosomal recessive disorder characterized by onset of generalized seizures between 5 and 10 years, and subsequent progressive mental retardation3. Here we report the positional cloning of a novel gene, CLN8, which is mutated in EPMR. It encodes a putative transmembrane protein. EPMR patients were homozygous for a missense mutation (70C→G, R24G) that was not found in homozygosity in 433 controls. We also cloned the mouse Cln8 sequence. It displays 82% nucleotide identity with CLN8, conservation of the codon harbouring the human mutation and is localized to the same region as the motor neuron degeneration mouse, mnd, a naturally occurring mouse NCL (ref. 4). In mnd/mnd mice, we identified a homozygous 1-bp insertion (267-268insC, codon 90) predicting a frameshift and a truncated protein. Our data demonstrate that mutations in these orthologous genes underlie NCL phenotypes in human and mouse, and represent the first description of the molecular basis of a naturally occurring animal model for NCL.