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In this study, atom probe tomography (APT) was used to investigate strontium-containing bioactive glass particles (BG-Sr10) and strontium-releasing bioactive glass-based scaffolds (pSrBG), both of which are attractive biomaterials with applications in critical bone damage repair. We outline the challenges and corresponding countermeasures of this nonconductive biomaterial for APT sample preparation and experiments, such as avoiding direct contact between focussed ion beam micromanipulators and the extracted cantilever to reduce damage during liftout. Using a low imaging voltage (≤3 kV) and current (≤500 pA) in the scanning electron microscope and a low acceleration voltage (≤2 kV) and current (≤200 pA) in the focussed ion beam prevents tip bending in the final stages of annular milling. To optimize the atom probe experiment, we considered five factors: total detected hits, multiple hits, the background level, the charge-state ratio, and the accuracy of the measured compositions, to explore the optimal laser pulse for BG-Sr10 bioactive glass. We show that a stage temperature of 30 K, 200–250 pJ laser pulse energy, 0.3% detection rate, and 200 kHz pulse rate are optimized experimental parameters for bioactive glass. The use of improved experimental preparation methods and optimized parameters resulted in a 90% successful yield of pSrBG samples by APT.

Barrier membranes are an essential tool in guided bone Regeneration (GBR), which have been widely presumed to have a bioactive effect that is beyond their occluding and space maintenance functionalities. A standardized calvaria implantation model was applied for 2, 8, and 16 weeks on Wistar rats to test the interactions between the barrier membrane and the underlying bone defects which were filled with bovine bone substitute materials (BSM). In an effort to understand the barrier membrane’s bioactivity, deeper histochemical analyses, as well as the immunohistochemical detection of macrophage subtypes (M1/M2) and vascular endothelial cells, were conducted and combined with histomorphometric and statistical approaches. The native collagen-based membrane was found to have ossified due to its potentially osteoconductive and osteogenic properties, forming a “bony shield” overlying the bone defects. Histomorphometrical evaluation revealed the resorption of the membranes and their substitution with bone matrix. The numbers of both M1- and M2-macrophages were significantly higher within the membrane compartments compared to the underlying bone defects. Thereby, M2-macrophages significantly dominated the tissue reaction within the membrane compartments. Statistically, a correlation between M2-macropahges and bone regeneration was only found at 2 weeks post implantationem, while the pro-inflammatory limb of the immune response correlated with the two processes at 8 weeks. Altogether, this study elaborates on the increasingly described correlations between barrier membranes and the underlying bone regeneration, which sheds a light on the understanding of the immunomodulatory features of biomaterials.

Cytocompatibility analyses of new implant materials or biomaterials are not only prescribed by the Medical Device Regulation (MDR), as defined in the DIN ISO Norm 10993-5 and -12, but are also increasingly replacing animal testing. In this context, jellyfish collagen has already been established as an alternative to mammalian collagen in different cell culture conditions, but a lack of knowledge exists about its applicability for cytocompatibility analyses of biomaterials. Thus, the present study was conducted to compare well plates coated with collagen type 0 derived from Rhizostoma pulmo with plates coated with bovine and porcine collagen. The coated well plates were analysed in vitro for their cytocompatibility, according to EN ISO 10993-5/−12, using both L929 fibroblasts and MC3T3 pre-osteoblasts. Thereby, the coated well plates were compared, using established materials as positive controls and a cytotoxic material, RM-A, as a negative control. L929 cells exhibited a significantly higher viability (#### p < 0.0001), proliferation (## p < 0.01), and a lower cytotoxicity (## p < 0.01 and # p < 0.05)) in the Jellagen® group compared to the bovine and porcine collagen groups. MC3T3 cells showed similar viability and acceptable proliferation and cytotoxicity in all collagen groups. The results of the present study revealed that the coating of well plates with collagen Type 0 derived from R. pulmo leads to comparable results to the case of well plates coated with mammalian collagens. Therefore, it is fully suitable for the in vitro analyses of the cytocompatibility of biomaterials or medical devices.

Background: Bioglass is a highly adoptable bone substitute material which can be combined with so-called therapeutic ions. However, knowledge is poor regarding the influence of therapeutic ions on immune reactions and associated bone healing. Thus, the aim of this work was to investigate the influence of strontium- and copper-doped bioglass on the induction of M1 and M2 macrophages, as well as vascularization. Materials and Methods: Two types of alkali glass were produced based on ICIE16 bioglass via the melt-quench method with the addition of 5 wt% copper or strontium (ICIE16-Cu and ICIE16-Sr). Pure ICIE16 and 45S5 bioglass were used as control materials. The ion release and chemical composition of the bioglass were investigated, and an in vivo experiment was subcutaneously performed on Sprague–Dawley rats. Results: Scanning electron microscopy revealed significant differences in the surface morphology of the bioglass materials. Energy dispersive X-ray spectroscopy confirmed the efficiency of the doping process by showing the ion-release kinetics. ICIE16-Cu exhibited a higher ion release than ICIE16-Sr. ICIE16-Cu induced low immune cell migration and triggered not only a low number of M1 and M2 macrophages but also of blood vessels. ICIE16-Sr induced higher numbers of M1 macrophages after 30 days. Both bioglass types induced numbers of M2 macrophages comparable with those found in the control groups. Conclusion: Bioglass doping with copper and strontium did not significantly influence the foreign body response nor vascularization of the implantation bed in vivo. However, all the studied bioglass materials seemed to be biocompatible.

Although various studies have investigated differences in the tissue reaction pattern to synthetic and xenogeneic bone substitute materials (BSMs), a lack of knowledge exists regarding the classification of both materials based on the DIN ISO 10993-6 scoring system, as well as the histomorphometrical measurement of macrophage subtypes within their implantation beds. Thus, the present study was conducted to analyze in vivo responses to both xenogeneic and synthetic bone substitute granules. A standardized calvaria implantation model in Wistar rats, in combination with established scoring, histological, histopathological, and histomorphometrical methods, was conducted to analyze the influence of both biomaterials on bone regeneration and the immune response. The results showed that the application of the synthetic BSM maxresorb® induced a higher pro-inflammatory tissue response, while the xenogeneic BSM cerabone® induced a higher anti-inflammatory reaction. Additionally, comparable bone regeneration amounts were found in both study groups. Histopathological scoring revealed that the synthetic BSM exhibited non-irritant scores at all timepoints using the xenogeneic BSM as control. Overall, the results demonstrated the biocompatibility of synthetic BSM maxresorb® and support the conclusion that this material class is a suitable alternative to natural BSM, such as the analyzed xenogeneic material cerabone®, for a broad range of indications.

Bioglasses are highly adoptable bone substitute materials, which can be combined with so-called therapeutic ions. These ions have shown to influence underlying molecular processes of the bone regeneration cascade. Moreover, it is known that bone substitutes induce an immune reaction within their implantation area involving macrophages and their pro- and anti-inflammatory subtypes dependent on their chemical composition. However, only poor knowledge exists regarding the influence of therapeutic ions onto the immune reactions and the associated bone healing. Thus, the aim of this work was to investigate the influence of strontium- and copper-doped bioglasses on the induction of M1- and M2-macrophages as well as the implant bed vascularization. (2) Methods: For this study, two alkali glasses were produced on basis of ICIE-16 bioglass via the melt-quench route with the addition of 5 wt% copper or strontium (ICIE16-Cu and ICIE16-Sr). Pure ICIE16 and 45S5 bioglasses were used as control materials. The bioactivity (ion release), chemical composition and the surface pattern were investigated, as well as an in vivo experiment was performed using the subcutaneous implantation model in rats. (3) Results: SEM imaging showed different formations of hydroxyapatite on the surfaces of the bioglass systems after submersion in simulated body fluid. EDX analysis confirmed the doping process by showing the release kinetics. Copper-doped bioglass exhibited a higher ion release than strontium-doped bioglass. Copper induced both a low immune cell migration and triggered a low number of M1- and M2-macrophages but also of blood vessels. The strontium-containing bioactive glass induced higher numbers of M1-macrophages after 30 days. Both copper- and strontium-doped bioglasses induced comparable numbers of M2-macrophages as found in the control groups. (4) Conclusions: Bioglass doping with copper and strontium did not exhibit significant influence on the foreign body response or the implantation bed vascularization in vivo. However, the prepared bioglass systems seemed to be biocompatible.

In animals, early embryogenesis is maternally controlled, whereas in plants, parents contribute equally to the proembryo transcriptome. Thus, the question remains whether equivalent parental contribution to the transcriptome of the early proembryo means equal control of early embryogenesis. Here, on the basis of cell-lineage-specific and allele-specific transcriptome analysis, we reveal that paternal and maternal genomes contribute equally to the transcriptomes of both the apical cell lineage and the basal cell lineage of early proembryos. However, a strong maternal effect on basal cell lineage development was found, indicating that equal parental contribution to the transcriptome is not necessarily coupled with equivalent parental control of proembryonic development. Parental contributions to embryogenesis therefore cannot be concluded solely on the basis of the ratio of paternal/maternal transcripts. Furthermore, we demonstrate that parent-of-origin genes display developmental-stage-dependent and cell-lineage-dependent allelic expression patterns. These findings will facilitate the investigation of specific parental roles in specific processes of early embryogenesis.

The “green” production of bitumen has raised increasing interest in recent years to reduce the environmental, energy and petro-based concerns. Bio-oil, prepared by biomass pyrolysis, can be used as substitute for petro-based bitumen in bitumen or bitumen-based coatings, for its similar properties of good adhesion and anti-corrosion characteristics. Although biomass is a renewable and widespread chemicals resource, its value-added utilization is still difficult. Several studies have qualitatively demonstrated the use of bio-bitumen in practical applications. The present study investigates the effects and properties and the incorporation of bio-bitumen shown to improve the performance of traditional petro-bitumen to some extent. Bio-bitumen was prepared from biomass pyrolysis oil and applied to self-adhesive and doped hot-melt sheets. Resulting physical properties demonstrate that bio-bitumen is a potential substitute in bitumen coating sheet.IMPLICATIONSThis paper is intended to verify the effect of pyrolyzed bio-oil from wheat straw on the performance of bitumen, as well as the feasibility of application in the coating sheet. Up to now, the research on bio-bitumen is mainly in pavement bitumen. In the present research, bio-bitumen was applied to the coating sheet in different proportions. Interestingly, the prepared coating sheet exhibited higher adhesion. Other performances, such as temperature stability, mechanical strength and temperature flexibility of coating sheet showed improvement in the presence of bio- oil, which indicated the suitability of bio-oil in coating sheet bitumen.

Synthetic bone substitute materials (BSMs) are becoming the general trend, replacing autologous grafting for bone tissue engineering (BTE) in orthopedic research and clinical practice. As the main component of bone matrix, collagen type I has played a critical role in the construction of ideal synthetic BSMs for decades. Significant strides have been made in the field of collagen research, including the exploration of various collagen types, structures, and sources, the optimization of preparation techniques, modification technologies, and the manufacture of various collagen-based materials. However, the poor mechanical properties, fast degradation, and lack of osteoconductive activity of collagen-based materials caused inefficient bone replacement and limited their translation into clinical reality. In the area of BTE, so far, attempts have focused on the preparation of collagen-based biomimetic BSMs, along with other inorganic materials and bioactive substances. By reviewing the approved products on the market, this manuscript updates the latest applications of collagen-based materials in bone regeneration and highlights the potential for further development in the field of BTE over the next ten years.

Infection-related titanium implant failure rates remain exceedingly high in the clinic. Functional surface coating represents a very promising strategy to improve the antibacterial and bioactive properties of titanium alloy implants. Here, we describe a novel bioactive surface coating that consists of a mussel-inspired carboxymethyl chitosan hydrogel loaded with silver nanoparticles (AgNPs) to enhance the bioactive properties of the titanium alloy. The preparation of hydrogel is based on gallic acid grafted carboxymethyl chitosan (CMCS-GA) catalyzed by DMTMM (4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride). To build a firm bonding between the hydrogel and titanium alloy plate, a polydopamine layer was introduced onto the surface of the titanium alloy. With HRP/H2O2 catalysis, CMCS-GA can simply form a firm gel layer on the titanium alloy plate through the catechol groups. The surface properties of titanium alloy were characterized by scanning electron microscope (SEM), X-ray photoelectron spectroscopy (XPS), and water contact angle. Silver nanoparticles were loaded into the gel layer by in situ reduction to enhance the antibacterial properties. In vitro antibacterial and cell viability experiments showed that the AgNPs-loaded Ti-gel possesses excellent antibacterial properties and did not affect the proliferation of rabbit mesenchymal stem cells (MSCs).

The ocean covers more than 70% of the global area and contains rich resources. Marine exploration has attracted more and more attention due to its scientific, strategic and economic importance, and one of the necessary conditions for marine exploration and development is the ability to have underwater communication. Underwater acoustic communication is a relatively mature means of communication at present, but due to the influence of multipath interference and Doppler effect, the underwater communication transmission bandwidth is small, the time delay is high, and can not meet the needs of high-speed transmission. Underwater wireless optical communication (UWOC) can provide large bandwidth transmission, low latency and high security. However, the scattering characteristics of seawater to light cause time-domain dispersion, which limits the channel bandwidth. In addition, the influence of optoelectronic modulation and devices limits the bandwidth of receiver and transmitter. In recent years, underwater wireless communication technology has attracted much attention, and its application in the field of ocean engineering has broad prospects, such as underwater high-definition video transmission and deep sea observation, so the realization of high-speed underwater wireless communication system has become an urgent problem to be solved.

Guided bone regeneration (GBR) has become a clinically standard modality for the treatment of localized jawbone defects. Barrier membranes play an important role in this process by preventing soft tissue invasion outgoing from the mucosa and creating an underlying space to support bone growth. Different membrane types provide different biological mechanisms due to their different origins, preparation methods and structures. Among them, collagen membranes have attracted great interest due to their excellent biological properties and desired bone regeneration results to non-absorbable membranes even without a second surgery for removal. This work provides a comparative summary of common barrier membranes used in GBR, focusing on recent advances in collagen membranes and their biological mechanisms. In conclusion, the review article highlights the biological and regenerative properties of currently available barrier membranes with a particular focus on bioresorbable collagen-based materials. In addition, the advantages and disadvantages of these biomaterials are highlighted, and possible improvements for future material developments are summarized.

Dihydrotanshinone I (DHT) is a natural component in Salvia miltiorrhiza and has been widely researched for its multiple bioactivities. However, poor solubility and biocompatibility of DHT limit its desirable application for clinical purposes. Herein, DHT was encapsulated with bovine serum albumin (BSA) to enhance bioavailability. Compared to free DHT, DHT–BSA NPs (nanoparticles) showed an improved solubility in normal saline and increased protection against hydrogen peroxide–induced oxidative damage in PC12 cells. In addition, DHT–BSA NPs administered by intravenous injection displayed a significant efficacy in the middle cerebral artery occlusion/reperfusion models, without any impact on the cerebral blood flow. In summary, DHT–BSA NPs show an enhanced bioavailability compared with free DHT and a successful penetration into the central nervous system for stroke therapy, demonstrating their application potential in cardio–cerebrovascular diseases.

Many researchers have shown that it is engineering feasible to use fiber-reinforced polymer (FRP) bars instead of steel bars as the tension-affected main bars in reinforced concrete structures. However, concrete slabs strengthened with FRP bars are limited in the field of civil engineering. For example, the elastic modulus of FRP bars is low, and the ductility of the member is reduced due to the brittleness of FRP bars. To solve these problems as much as possible, scholars have adopted an idea that can use both FRP bars and steel bars in concrete members. There are still some problems with the bending behavior and durability of the proposed structural reinforcement, and further research is needed in this area. In this paper, the concrete slabs strengthened with GFRP reinforcement and reinforced mixing on the bending properties and durability of the experimental research, and some important findings are summarized.

Vegetable oil is a major edible oil and an important industrial raw material. However, breeders have found it challenging to improve the oil content of crop seeds, and little is known about regulators with the potential to increase oil content via molecular engineering in modern oil crop breeding. We reported an F-box protein, Arabidopsis thaliana MYB Interaction Factor 1 (AtMIF1), which is a member of the ubiquitin-protein ligase E3 complex involved in the 26S proteasome protein degradation pathway. AtMIF1 physically interacts with MYB domain protein 5 (MYB5), which results in MYB5 degradation, so that transcriptional activation of the MYB/bHLH/WD-repeat (MBW) complex does not occur normally and GLABRA2 (GL2), encoding an inhibitor of oil content and functioning as a direct downstream gene of MBW, is not properly transcribed. AtMIF1 functioned as a positive regulator that increases oil content by attenuating GL2 inhibition. We overexpressed AtMIF1 and obtained transgenic plants with significantly higher seed oil contents. Importantly, both vegetative and reproductive growth of the transgenic plants appeared normal. In summary, this work reveals a novel regulator, AtMIF1, and a new regulatory pathway, 26S proteasome-AtMIF1-MYB5, for increasing the oil content of seeds without affecting plant growth, thus facilitating oil crop breeding.

Papermaking waste liquid (black liquor) is a serious source of water pollution worldwide. The subsequent treatment of it is very difficult cause it contains a large amount of lignin, inorganic salts, organic matter, and pigments, which lead to serious water pollution. Lignin is the main by-product of the paper industry and is the only natural aromatic recyclable resource. Its effective utilization rate is currently less than 3%. Therefore, how to effectively recycle lignin in papermaking waste liquid and further synthesize industrialized products is of great significance to the sustainable development and environmental protection. Besides, based on the shortage of petroleum resources in recent years, the application of biomass resources instead of petroleum resources in the industry is also an important issue. In this article, we explored the best optimal conditions for the oxypropylation and esterification of lignin, and prepared bio-bitumen based on modified lignin, and then applied it to the waterproof coating sheets. FTIR and mechanical properties (softening point, low-temperature flexibility, peel strength, etc.) were tested on the obtained waterproof coating sheets. The results show that the addition of modified lignin reduced the softening point and peel strength of the coating sheets. Interestingly, both oxypropylated lignin (OL) and esterified lignin (OEL) were very beneficial to resist the decrease in peel strength during the aging process, showing a significant improvement in the performance of the coating sheets after aging compared to the control.

The microstructure of the surface oxide film formed on an Fe-9Cr Ferritic-Martensitic (F-M) steel after exposure to deaerated high-temperature steam at 600°C for 100 h has been analyzed in detail by advanced characterization techniques. The surface oxide film has been revealed to have a triplex structure, including an outer oxide layer, an inner oxide layer, and an internal oxide layer. Although the outer and inner oxide layers are continuous, the internal oxide layer has been proved to consist of interconnected metallic and chromite phases, which is a typical feature of internal oxidation. The formation mechanisms of each layer have been discussed, finding that, contrary to what the available space model suggests, an external oxidation is not the controlling oxidation mechanism of F-M steels in high-temperature steam. The higher resolution used in this study confirms that the controlling mechanism is internal oxidation.

In animals, early embryogenesis is maternally controlled, whereas in plants, parents contribute equally to the proembryo transcriptome. Thus, the question remains whether equivalent parental contribution to the transcriptome of the early proembryo means equal control of early embryogenesis. Here, on the basis of cell-lineage-specific and allele-specific transcriptome analysis, we reveal that paternal and maternal genomes contribute equally to the transcriptomes of both the apical cell lineage and the basal cell lineage of early proembryos. However, a strong maternal effect on basal cell lineage development was found, indicating that equal parental contribution to the transcriptome is not necessarily coupled with equivalent parental control of proembryonic development. Parental contributions to embryogenesis therefore cannot be concluded solely on the basis of the ratio of paternal/maternal transcripts. Furthermore, we demonstrate that parent-of-origin genes display developmental-stage-dependent and cell-lineage-dependent allelic expression patterns. These findings will facilitate the investigation of specific parental roles in specific processes of early embryogenesis.

This study was aimed at optimising the composition of recycled plastic based composite for improving mechanical performance. The fractions of virgin polypropylene (vPP), talcum powder (talc) and maleic anhydride grafted polypropylene (MAPP) were selected as controllable factors. Taguchi L9 (33) orthogonal array (OA) was applied as an experimental design tool. Compositions were prepared by extrusion and injection moulding. The performance was measured and expressed in signal to noise (S/N) ratio. The S/N ratios were investigated by the Taguchi coupled analysis of variance (ANOVA) to determine optimal condition. The effectiveness and efficiency of the proposed approach was demonstrated through confirmation tests.

Objective Baicalin, which is isolated from Scutellariae Radix, has been shown to possess therapeutic potential for different diseases. Cardiac microvessel injury in myocardial ischemia–reperfusion (IR) has been extensively explored. However, there have been no studies investigating the physiological regulatory mechanisms of baicalin on nitric oxide production and the necroptosis of cardiac microvascular endothelial cells (CMECs) in myocardial IR injury. This study was designed to investigate the contribution of baicalin to repressing necroptosis and preventing IR-mediated CMEC dysfunction. Materials and Methods Indicators of ventricular structure and function were measured by an echocardiographic system. An MTT assay was performed to assess cell viability. Nitrite detection was performed to detect nitric oxide content, and cGMP content was determined using a commercially available cGMP complete ELISA kit. Morphology and molecular characteristics were detected by electron micrographs, quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. Result Our results demonstrated that baicalin significantly improved cardiac function, decreased the myocardial infarction area, and inhibited myocardial cell apoptosis. Moreover, baicalin had a protective effect on cardiac microvessels and promoted the production of nitric oxide (NO) and the level of cGMP in rats that underwent myocardial IR injury. The results of the in vitro experiments showed that baicalin markedly improved cell activity and function in CMECs exposed to hypoxia-reoxygenation (HR). Further experiments indicated that baicalin supplementation suppressed the protein expression of RIP1, RIP3 and p-MLKL to interrupt CMEC necroptosis. In addition, baicalin promoted the production of NO via activating the PI3K-AKT-eNOS signaling pathway. Taken together, our results identified the PI3K-AKT-eNOS axis as a new pathway responsible for reperfusion-mediated microvascular damage. Conclusion Baicalin protected CMECs in IR rats by promoting the release of NO via the PI3K-AKT-eNOS pathway and mitigated necroptosis by inhibiting the protein expression of RIP1, RIP3 and p-MLKL.

Polyethylene (PE) is one of the most widespread plastic materials. Nevertheless, due to its recalcitrance against biological degradation and the presence of toxic additives, landfilled and carelessly disposed PE products have caused serious pollution in the natural environments. In this work, we aimed to investigate the growth characteristics of Microbulbifer hydrolyticus IRE-31 and its application in the biological degradation of low-density PE. The IRE-31 strain was isolated from marine pulp mill wastes rich in lignin which is a natural complex polymer containing also saturated carbon-carbon bonds like in PE. Following 30 days cultivation of the IRE-31 strain, the biodegradation of linear low-density PE particles was evidenced clearly by morphological changes of the polymer surface monitored by scanning electron microscopy and the formation of additional carbonyl groups in the polymer chains indicated by Fourier transform infrared spectroscopy.

Human cancer cells typically harbour multiple chromosomal aberrations, nucleotide substitutions and epigenetic modifications that drive malignant transformation. The Cancer Genome Atlas ( TCGA) pilot project aims to assess the value of large- scale multi- dimensional analysis of these molecular characteristics in human cancer and to provide the data rapidly to the research community. Here we report the interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas - the most common type of primary adult brain cancer - and nucleotide sequence aberrations in 91 of the 206 glioblastomas. This analysis provides new insights into the roles of ERBB2, NF1 and TP53, uncovers frequent mutations of the phosphatidylinositol- 3- OH kinase regulatory subunit gene PIK3R1, and provides a network view of the pathways altered in the development of glioblastoma. Furthermore, integration of mutation, DNA methylation and clinical treatment data reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated glioblastomas, an observation with potential clinical implications. Together, these findings establish the feasibility and power of TCGA, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer.

The rhesus macaque ( Macaca mulatta ) is an abundant primate species that diverged from the ancestors of Homo sapiens about 25 million years ago. Because they are genetically and physiologically similar to humans, rhesus monkeys are the most widely used nonhuman primate in basic and applied biomedical research. We determined the genome sequence of an Indian-origin Macaca mulatta female and compared the data with chimpanzees and humans to reveal the structure of ancestral primate genomes and to identify evidence for positive selection and lineage-specific expansions and contractions of gene families. A comparison of sequences from individual animals was used to investigate their underlying genetic diversity. The complete description of the macaque genome blueprint enhances the utility of this animal model for biomedical research and improves our understanding of the basic biology of the species.

Magnetic relaxations have been measured for up to 20 h for a flux-grown YBa 2 Cu 3 O 7- δ single crystal, with the applied field (up to 7 T) parallel to the c -axis. A ln( t ) relaxation of the magnetisation, found from the Anderson-Kim flux creep model, only describes our data for low temperatures and low fields. However, we have found that a power-law relaxation ( M )( t )∝ t -α ), which points to a logarithmic current-dependence of the effective activation energy [ U ( J )= U 0 ln ( J 0 / J )], fits the data well for a wide range of temperatures and applied fields. Values for U 0 ( B, T ) have been obtained from the power-law relation, and compared with the values derived from the logarithmic relaxation rates. Discrepancies between them are discussed. Possible connections between our experimental data and Feigel'man's collective flux creep theory are also discussed.

Background We present here the assembly of the bovine genome. The assembly method combines the BAC plus WGS local assembly used for the rat and sea urchin with the whole genome shotgun (WGS) only assembly used for many other animal genomes including the rhesus macaque. Results The assembly process consisted of multiple phases: First, BACs were assembled with BAC generated sequence, then subsequently in combination with the individual overlapping WGS reads. Different assembly parameters were tested to separately optimize the performance for each BAC assembly of the BAC and WGS reads. In parallel, a second assembly was produced using only the WGS sequences and a global whole genome assembly method. The two assemblies were combined to create a more complete genome representation that retained the high quality BAC-based local assembly information, but with gaps between BACs filled in with the WGS-only assembly. Finally, the entire assembly was placed on chromosomes using the available map information. Over 90% of the assembly is now placed on chromosomes. The estimated genome size is 2.87 Gb which represents a high degree of completeness, with 95% of the available EST sequences found in assembled contigs. The quality of the assembly was evaluated by comparison to 73 finished BACs, where the draft assembly covers between 92.5 and 100% (average 98.5%) of the finished BACs. The assembly contigs and scaffolds align linearly to the finished BACs, suggesting that misassemblies are rare. Genotyping and genetic mapping of 17,482 SNPs revealed that more than 99.2% were correctly positioned within the Btau_4.0 assembly, confirming the accuracy of the assembly. Conclusion The biological analysis of this bovine genome assembly is being published, and the sequence data is available to support future bovine research.

To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production. Fil: Bovine Genome Sequencing and Analysis Consortium. Bovine Genome Sequencing And Analysis Consortium; Estados Unidos Fil: Amadio, Ariel Fernando. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Santa Fe. Estación Experimental Agropecuaria Rafaela; Argentina Fil: Poli, Mario Andres. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Genética; Argentina

Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers--including NF1, APC, RB1 and ATM--and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.

Atlas is a suite of programs developed for assembly of genomes by a “combined approach” that uses DNA sequence reads from both BACs and whole-genome shotgun (WGS) libraries. The BAC clones afford advantages of localized assembly with reduced computational load, and provide a robust method for dealing with repeated sequences. Inclusion of WGS sequences facilitates use of different clone insert sizes and reduces data production costs. A core function of Atlas software is recruitment of WGS sequences into appropriate BACs based on sequence overlaps. Because construction of consensus sequences is from local assembly of these reads, only small (overlapper and split-scaffold are also being used in pure WGS projects.

The laboratory rat (Rattus norvegicus) is an indispensable tool in experimental medicine and drug development, having made inestimable contributions to human health. We report here the genome sequence of the Brown Norway (BN) rat strain. The sequence represents a high-quality 'draft' covering over 90% of the genome. The BN rat sequence is the third complete mammalian genome to be deciphered, and three-way comparisons with the human and mouse genomes resolve details of mammalian evolution. This first comprehensive analysis includes genes and proteins and their relation to human disease, repeated sequences, comparative genome-wide studies of mammalian orthologous chromosomal regions and rearrangement breakpoints, reconstruction of ancestral karyotypes and the events leading to existing species, rates of variation, and lineage-specific and lineage-independent evolutionary events such as expansion of gene families, orthology relations and protein evolution.

In order to study how Mn substitution changes the superconducting properties of the TlBaCaCuO compound, we have prepared samples with Mn in place of Cu, Tl and Ca respectively by solid-state reactions. We have examined their superconductive transitions by measurements of their resistive and magnetic behaviors, which show that Mn has a negative effect on the superconductivity. It has been found by energy dispersive spectrometry (EDS) and by secondary-ion mass spectrometry (SIMS) that even a relatively small amount of Mn can cause a significant loss of Cu and Tl in the Tl compound. X-ray diffraction and morphological analysis have shown that Mn can also bring in precipitated phases of BaCuO 2 and MnO 2 .

The imprints of domestication and breed development on the genomes of livestock likely differ from those of companion animals. A deep draft sequence assembly of shotgun reads from a single Hereford female and comparative sequences sampled from six additional breeds were used to develop probes to interrogate 37,470 single-nucleotide polymorphisms (SNPs) in 497 cattle from 19 geographically and biologically diverse breeds. These data show that cattle have undergone a rapid recent decrease in effective population size from a very large ancestral population, possibly due to bottlenecks associated with domestication, selection, and breed formation. Domestication and artificial selection appear to have left detectable signatures of selection within the cattle genome, yet the current levels of diversity within breeds are at least as great as exists within humans.

Background Rhesus macaques are the most widely utilized nonhuman primate model in biomedical research. Previous efforts have validated fewer than 900 single nucleotide polymorphisms (SNPs) in this species, which limits opportunities for genetic studies related to health and disease. Extensive information about SNPs and other genetic variation in rhesus macaques would facilitate valuable genetic analyses, as well as provide markers for genome-wide linkage analysis and the genetic management of captive breeding colonies. Results We used the available rhesus macaque draft genome sequence, new sequence data from unrelated individuals and existing published sequence data to create a genome-wide SNP resource for Indian-origin rhesus monkeys. The original reference animal and two additional Indian-origin individuals were resequenced to low coverage using SOLiD™ sequencing. We then used three strategies to validate SNPs: comparison of potential SNPs found in the same individual using two different sequencing chemistries, and comparison of potential SNPs in different individuals identified with either the same or different sequencing chemistries. Our approach validated approximately 3 million SNPs distributed across the genome. Preliminary analysis of SNP annotations suggests that a substantial number of these macaque SNPs may have functional effects. More than 700 non-synonymous SNPs were scored by Polyphen-2 as either possibly or probably damaging to protein function and these variants now constitute potential models for studying functional genetic variation relevant to human physiology and disease. Conclusions Resequencing of a small number of animals identified greater than 3 million SNPs. This provides a significant new information resource for rhesus macaques, an important research animal. The data also suggests that overall genetic variation is high in this species. We identified many potentially damaging non-synonymous coding SNPs, providing new opportunities to identify rhesus models for human disease.