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Structural Health Monitoring (SHM) provides the facilities for in-service monitoring of structural performance and damage assessment, and is a key element of condition based maintenance and damage prognosis. This comprehensive book brings readers up to date on the most important changes and advancements in the structural health monitoring technologies applied to civil engineering structures. It covers all aspects required for such monitoring in the field, including sensors and networks, data acquisition and processing, damage detection techniques and damage prognostics techniques. The book also includes a number of case studies showing how the techniques can be applied in the development of sustainable and resilient civil infrastructure systems. This book offers in-depth chapter coverage of: Sensors and Sensing Technology for Structural Monitoring; Data Acquisition, Transmission, and Management; Structural Damage Identification Techniques; Modal Analysis of Civil Engineering Structures; Finite Element Model Updating; Vibration Based Damage Identification Methods; Model Based Damage Assessment Methods; Monitoring Based Reliability Analysis and Damage Prognosis; and Applications of SHM Strategies to Large Civil Structures.

The design of atomic-scale microstructural traps to limit the diffusion of hydrogen is one key strategy in the development of hydrogen-embrittlement-resistant materials. In the case of bearing steels, an effective trapping mechanism may be the incorporation of finely dispersed V-Mo-Nb carbides in a ferrite matrix. First, we charged a ferritic steel with deuterium by means of electrolytic loading to achieve a high hydrogen concentration. We then immobilized it in the microstructure with a cryogenic transfer protocol before atom probe tomography (APT) analysis. Using APT, we show trapping of hydrogen within the core of these carbides with quantitative composition profiles. Furthermore, with this method the experiment can be feasibly replicated in any APT-equipped laboratory by using a simple cold chain.

Structures of voltage-gated sodium channelsIn “excitable” cells, like neurons and muscle cells, a difference in electrical potential is used to transmit signals across the cell membrane. This difference is regulated by opening or closing ion channels in the cell membrane. For example, mutations in human voltage-gated sodium (Nav) channels are associated with disorders such as chronic pain, epilepsy, and cardiac arrhythmia. Pan et al. report the high-resolution structure of a human Nav channel, and Shen et al. report the structures of an insect Nav channel bound to the toxins that cause pufferfish and shellfish poisoning in humans. Together, the structures give insight into the molecular basis of sodium ion permeation and provide a path toward structure-based drug discovery.Science, this issue p. eaau2486, p. eaau2596INTRODUCTIONThe nine subtypes of mammalian voltage-gated sodium (Nav) channels, Nav1.1 to Nav1.9, are responsible for the initiation and propagation of action potentials in specific excitable systems, among which Nav1.4 functions in skeletal muscle. Responding to membrane potential changes, Nav channels undergo sophisticated conformational shifts that lead to transitions between resting, activated, and inactivated states. Defects in Nav channels are associated with a variety of neurological, cardiovascular, muscular, and psychiatric disorders. In addition, Nav channels are targets for natural toxins and clinical therapeutics.Understanding the physiological and pathophysiological mechanisms of Nav channels requires knowing the structure of each conformational state. All eukaryotic Nav channels comprise a single polypeptide chain, the α subunit, that folds to four homologous repeats I to IV. Channel properties are modulated by one or two subtype-specific β subunits. Cryo–electron microscopy (cryo-EM) structures of two Nav channels, one from American cockroach and the other from electric eel, were resolved in two distinct conformations. However, the inability to record currents of either channel in heterologous systems prevented functional assignment of these structures. Structural elucidation of a functionally well-characterized Nav channel is required to establish a model for structure-function relationship studies.RATIONALEAfter extensive screening for expression systems, protein boundaries, chimeras, affinity tags, and combination with subtype-specific β subunits, we focused on human Nav1.4 in the presence of β1 subunit for cryo-EM analysis. The complex, which was transiently coexpressed in human embryonic kidney (HEK) 293F cells with BacMam viruses and purified through tandem affinity columns and size exclusion chromatography, was concentrated to ~0.5 mg/ml for cryo-EM sample preparation and data acquisition.RESULTSThe cryo-EM structure of human Nav1.4-β1 complex was determined to 3.2-Å resolution. The extracellular and transmembrane domains, including the complete pore domain, all four voltage-sensing domains (VSDs), and the β1 subunit, were clearly resolved, enabling accurate model building (see the figure).The well-resolved Asp/Glu/Lys/Ala (DEKA) residues, which are responsible for specific Na+ permeation through the selectivity filter, exhibit identical conformations to those seen in the other two Nav structures. A glyco-diosgenin (GDN) molecule, the primary detergent used for protein purification and cryo-EM sample preparation, penetrates the intracellular gate of the pore domain, holding it open to a diameter of ~5.6 Å. The central cavity of the pore domain is filled with lipid-like densities, which traverse the side wall fenestrations.Voltage sensing involves four to six Arg/Lys residues on helix S4 of the VSD. This helix moves “up” (away from the cytoplasm) in response to changes of the membrane potential, and this opens the channel finally. All four VSDs display up conformations. The movement of the gating charge residues is facilitated by coordination to acidic and polar residues on S1 to S3. The improved resolution allows detailed analysis of the coordination.The fast inactivation Ile/Phe/Met (IFM) motif on the short linker between repeats III and IV inserts into a hydrophobic cavity enclosed by the S6 and S4-S5 segments in repeats III and IV. Analysis of reported functional residues and disease mutations corroborates our recently proposed allosteric blocking mechanism for fast inactivation.CONCLUSIONThe structure provides important insight into the molecular basis for Na+ permeation, electromechanical coupling, asynchronous activation, and fast inactivation of the four repeats. It opens a new chapter for studying the structure-function relationships of Nav channels, affords an accurate template to map mutations associated with diseases such as myotonia and periodic paralysis hyperkalemic, and illuminates a path toward precise understanding and intervention with specific Nav channelopathies.Voltage-gated sodium (Nav) channels, which are responsible for action potential generation, are implicated in many human diseases. Despite decades of rigorous characterization, the lack of a structure of any human Nav channel has hampered mechanistic understanding. Here, we report the cryo–electron microscopy structure of the human Nav1.4-β1 complex at 3.2-Å resolution. Accurate model building was made for the pore domain, the voltage-sensing domains, and the β1 subunit, providing insight into the molecular basis for Na+ permeation and kinetic asymmetry of the four repeats. Structural analysis of reported functional residues and disease mutations corroborates an allosteric blocking mechanism for fast inactivation of Nav channels. The structure provides a path toward mechanistic investigation of Nav channels and drug discovery for Nav channelopathies.

A cap-specific m6A writerN6,2′-O-dimethyladenosine (m6Am) is present at the transcription start nucleotide of capped mRNAs in vertebrates. Akichika et al. quantified the abundance of this modification in the transcriptome and identified the writer protein, cap-specific adenosine methyltransferase (CAPAM), needed for this modification. CAPAM contains a unique structure that recognizes cap-specific N6-methyladenosine (m6A) as the substrate. The protein interacts with RNA polymerase II, suggesting that the modification occurs cotranscriptionally. The m6Am promotes the translation of capped mRNAs in a eIF4E-independent fashion.Science, this issue p. eaav0080INTRODUCTIONN6-methyladenosine (m6A), an abundant modification in eukaryotic mRNAs and long-noncoding RNAs, has been recognized as a major epitranscriptome mark that plays critical roles in RNA metabolism and function. In addition to the internal m6A, N6, 2′-O-dimethyladenosine (m6Am) is present at the transcription start site of capped mRNAs in vertebrates. Previous studies reported that an eraser protein, FTO, demethylates N6-methyl group of m6Am and destabilizes a subset of mRNAs, suggesting a possible function of m6Am in stabilizing A-starting capped mRNAs. However, the biogenesis and functional role of m6Am remain elusive.RATIONALETo reveal the functional and physiological roles of m6Am, it is necessary to identify a writer protein for N6-methylation of m6Am. We first established a highly sensitive method to analyze 5′-terminal chemical structures of the capped mRNAs using mass spectrometry (RNA-MS), and then measured m6Am methylation status accurately. We employed RNA-MS to identify the writer gene by a reverse genetic approach. We chose several candidates of uncharacterized methyltransferases (MTases) that are conserved in vertebrates, but not in yeast, which does not have m6Am. Each of the candidates was knocked out in human cells. If the target gene is disrupted, RNA-MS can detect the absence of m6Am in mRNAs prepared from the knockout cells.RESULTSRNA-MS analysis revealed that m6Am modification in human mRNAs is more abundant (92%) than previously estimated. We identified human PCIF1 as cap-specific adenosine-N6-MTase (CAPAM) responsible for N6-methylation of m6Am. Indeed, m6Am disappeared completely and converted to Am modification in mRNAs prepared from the CAPAM knockout (KO) cells. The CAPAM KO cells were viable, but sensitive to oxidative stress, implying the physiological importance of m6Am. We showed that CAPAM catalyzes N6-methylation of m6Am in the capped mRNAs in an S-adenosylmethionine (SAM)–dependent manner. A series of biochemical studies revealed that CAPAM specifically recognizes the 7-methylguanosine (m7G) cap structure and preferentially N6-methylates m7GpppAm rather than m7GpppA, indicating the importance of the 2′-O-methyl group of the target site for efficient m6Am formation. CAPAM has a N-terminal WW domain that specifically interacts with the Ser5-phosphorylated C-terminal domain (CTD) of RNA polymerase II (RNAPII), suggesting that the CAPAM is recruited to the early elongation complex of RNAPII and introduces m6Am in a nascent mRNA chain cotranscriptionally. We also solved the crystal structure of CAPAM complexed with the cap analog and SAM analog. The core region of CAPAM is composed of MTase and helical domains. The m7G cap is bound to a pocket formed by these two domains. The SAM analog is recognized by an active site with the characteristic NPPF motif in the MTase domain. This structure reveals the molecular basis of cap-specific m6A formation. RNA-sequencing analysis of the CAPAM KO cells revealed that loss of m6Am does not affect transcriptome alteration. This result does not support the proposed function of m6Am in stabilizing A-starting capped mRNAs. Instead, ribosome profiling of the CAPAM KO cells showed that N6-methylation of m6Am promotes the translation of capped mRNAs.CONCLUSIONWe identified PCIF1/CAPAM as a cap-specific m6A writer for vertebrate mRNAs. Structural analysis revealed the molecular basis of cap-specific m6A formation by CAPAM. The ribosome profiling experiment revealed that CAPAM-mediated m6Am formation promotes translation of A-starting mRNAs, rather than stabilization of mRNAs.N6-methyladenosine (m6A), a major modification of messenger RNAs (mRNAs), plays critical roles in RNA metabolism and function. In addition to the internal m6A, N6, 2′-O-dimethyladenosine (m6Am) is present at the transcription start nucleotide of capped mRNAs in vertebrates. However, its biogenesis and functional role remain elusive. Using a reverse genetics approach, we identified PCIF1, a factor that interacts with the serine-5–phosphorylated carboxyl-terminal domain of RNA polymerase II, as a cap-specific adenosine methyltransferase (CAPAM) responsible for N6-methylation of m6Am. The crystal structure of CAPAM in complex with substrates revealed the molecular basis of cap-specific m6A formation. A transcriptome-wide analysis revealed that N6-methylation of m6Am promotes the translation of capped mRNAs. Thus, a cap-specific m6A writer promotes translation of mRNAs starting from m6Am.

\"A concise, practical guide to structural design using steel, masonry, and timber Structural Design of Low-Rise Building in Cold-Formed Steel Reinforced Masonry, and Structural Timber authoritatively covers the primary aspects of structural design of low-rise buildings in the most common materials--cold-formed steel, reinforced masonry, and structural timber. Cold-formed steel was recently added to the NCEES (National Council of Examiners for Engineering and Surveying) structural exams, and this book also serves as a complete Professional Engineer/Structural Engineer exam study guide.Structural Design of Low-Rise Building in Cold-Formed Steel Reinforced Masonry, and Structural Timber Discusses concepts associated with day-to-day design Covers Steel Joist Institute (SJI) open-web joist systems Includes the most recent changes in fundamental code requirements pertaining to structural timber, reinforced masonry, and cold-formed steel Addresses loading requirements for low-rise buildings Presents the most important code changes pertaining to IBC-based design of structural masonry, cold-formed steel, and structural timber/wood\"--Provided by publisher.

When the DNA bases cytosine and guanine are next to each other, a methyl group is generally added to the pyrimidine, generating a mCpG dinucleotide. This modification alters DNA structure but can also affect function by inhibiting transcription factor (TF) binding. Yin et al. systematically analyzed the effect of CpG methylation on the binding of 542 human TFs (see the Perspective by Hughes and Lambert). In addition to inhibiting binding of some TFs, they found that mCpGs can promote binding of others, particularly TFs involved in development, such as homeodomain proteins. Science , this issue p. eaaj2239 ; see also p. 489 Genome-scale analysis reveals positive and negative binding of transcription factors to methylated CpG dinucleotides. The majority of CpG dinucleotides in the human genome are methylated at cytosine bases. However, active gene regulatory elements are generally hypomethylated relative to their flanking regions, and the binding of some transcription factors (TFs) is diminished by methylation of their target sequences. By analysis of 542 human TFs with methylation-sensitive SELEX (systematic evolution of ligands by exponential enrichment), we found that there are also many TFs that prefer CpG-methylated sequences. Most of these are in the extended homeodomain family. Structural analysis showed that homeodomain specificity for methylcytosine depends on direct hydrophobic interactions with the methylcytosine 5-methyl group. This study provides a systematic examination of the effect of an epigenetic DNA modification on human TF binding specificity and reveals that many developmentally important proteins display preference for mCpG-containing sequences.