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To enhance the design and research work on dynamic characteristics of high-rise laminated timber buildings, this paper carried out a modal analysis study on one of the largest laminated timber buildings in China. The finite element calculating modal analysis was carried out using SAP2000 software, and the experimental modal analysis of the building was carried out via environmental excitation. The calculating modal results and the experimental modal results showed good agreement. The calculating modal frequency values were generally lower than the experimental modal frequency values. The natural frequencies obtained by the two methods appeared in the Y-direction first-order bending mode and had values of 2.03 and 2.5 Hz, respectively. The corresponding frequencies of the first-order torsional mode were 2.82 and 3.25 Hz, respectively. The distribution of the CLT core tube along the length direction of the building has an impact on the vibration mode. The six-story part shows the second-order bending form, while the four-story section only shows the first-order bending form. The above work provides a case study and reference for the simulation and modal analysis of high-rise laminated timber buildings, demonstrating the critical role of the core tube structure in such wooden buildings. This insight contributes to a better understanding of structural performance and design considerations in similar projects. [ABSTRACT FROM AUTHOR]

Double minutes (DMs), extrachromosomal gene fragments found within certain tumors, have been noted to carry onco- and drug resistance genes contributing to tumor pathogenesis and progression. After screening for SUMO-related molecule expression within various tumor sample and cell line databases, we found that SUMO-conjugating enzyme UBC9 has been associated with genome instability and tumor cell DM counts, which was confirmed both in vitro and in vivo. Karyotyping determined DM counts post-UBC9 knockdown or SUMOylation inhibitor 2-D08, while RT-qPCR and Western blot were used to measure DMcarried gene expression in vitro. In vivo, fluorescence in situ hybridization (FISH) identified micronucleus (MN) expulsion. Western blot and immunofluorescence staining were then used to determine DNA damage extent, and a reporter plasmid system was constructed to detect changes in homologous recombination (HR) and non-homologous end joining (NHEJ) pathways. Our research has shown that UBC9 inhibition is able to attenuate DM formation and lower DM-carried gene expression, in turn reducing tumor growth and malignant phenotype, via MN efflux of DMs and lowering NHEJ activity to increase DNA damage. These findings thus reveal a relationship between heightened UBC9 activity, increased DM counts, and tumor progression, providing a potential approach for targeted therapies, via UBC9 inhibition. [ABSTRACT FROM AUTHOR]

Chemical benchmarking was used to investigate the temporal variation of the persistence of chemical contaminants in a Swedish lake. The chemicals studied included 12 pharmaceuticals, an artificial sweetener, and an X-ray contrast agent. Measurements were conducted in late spring, late autumn, and winter. The transformation half-life in the lake could be quantified for 7 of the chemicals. It ranged from several days to hundreds of days. For 5 of the chemicals (bezafibrate, climbazole, diclofenac, furosemide, and hydrochlorothiazide), the measured persistence was lower in late spring than in late autumn. This may have been caused by lower temperatures and/or less irradiation during late autumn. The seasonality in chemical persistence contributed to changes in chemical concentrations in the lake during the year. The impact of seasonality of persistence was compared with the impact of other important variables determining concentrations in the lake: chemical inputs and water flow/dilution. The strongest seasonal variability in chemical concentration in lake water was observed for hydrochlorothiazide (over a factor of 10), and this was attributable to the seasonality in its persistence. [ABSTRACT FROM AUTHOR]

It is challenging to measure the persistence of chemicals under field conditions. In this work, two approaches for measuring persistence in the field were compared: the chemical mass balance approach, and a novel chemical benchmarking approach. Ten pharmaceuticals, an X-ray contrast agent, and an artificial sweetener were studied in a Swedish lake. Acesulfame K was selected as a benchmark to quantify persistence using the chemical benchmarking approach. The 95% confidence intervals of the half-life for transformation in the lake system ranged from 780-5700 days for carbamazepine to <1-2 days for ketoprofen. The persistence estimates obtained using the benchmarking approach agreed well with those from the mass balance approach (1-21% difference), indicating that chemical benchmarking can be a valid and useful method to measure the persistence of chemicals under field conditions. Compared to the mass balance approach, the benchmarking approach partially or completely eliminates the need to quantify mass flow of chemicals, so it is particularly advantageous when the quantification of mass flow of chemicals is difficult. Furthermore, the benchmarking approach allows for ready comparison and ranking of the persistence of different chemicals. [ABSTRACT FROM AUTHOR]

Mature neurons have diminished intrinsic regenerative capacity. Axotomy of the peripheral branch of adult dorsal root ganglia (a "conditioning" lesion) triggers a transcription-dependent axon growth program. Here, we show that this growth program requires the function of the transcription factor Smad1. After peripheral axotomy, neuronal Smad1 is upregulated, and phosphorylated Smad1 accumulates in the nucleus. Both events precede the onset of axonal extension. Reducing Smad1 by RNA interference in vitro impairs axonal growth, and the continued presence of Smad1 is required to maintain the growth program. Furthermore, intraganglionic injection of BMP2 or 4, which activates Smad1, markedly enhances axonal growth capacity, mimicking the effect of a conditioning lesion. Thus, activation ofSmad1by axotomy is a key component of the transcriptional switch that promotes an enhanced growth state of adult sensory neurons. [ABSTRACT FROM AUTHOR]

Axon regeneration is hindered by a decline of intrinsic axon growth capability in mature neurons. Reversing this decline is associated with the induction of a large repertoire of regeneration-associated genes (RAGs), but the underlying regulatory mechanisms of the transcriptional changes are largely unknown. Here, we establish a correlation between diminished axon growth potential and histone 4 (H4) hypoacetylation. When neurons are triggered into a growth state, as in the conditioning lesion paradigm, H4 acetylation is restored, and RAG transcription is initiated. We have identified a set of target genes of Smad 1, a proregenerative transcription factor, in conditioned DRG neurons. We also show that, during the epigenetic reprogramming process, histone-modifying enzymes work together with Smadl to facilitate transcriptional regula-tion of RAGs. Importantly, targeted pharmacological modulation of the activity of histone-modifying enzymes, such as histone deacetylases, leads to induction of multiple RAGs and promotion of sensory axon regeneration in a mouse model of spinal cord injury. Our findings suggest epigenetic modulation as a potential therapeutic strategy to enhance axon regeneration. [ABSTRACT FROM AUTHOR]

The article offers information on a study that explores diversified transcriptional responses of myeloid and glial cells in spinal cord injury shaped by epigenetic regulator histone deacetylase 3 (HDAC3) activity. It mentions that diversification of myeloid and glial subtypes in spinal cord injury and an extensive influence of HDAC3.

The embryonic formation of midbrain dopaminergic (mDA) neurons in vivo provides critical guidelines for the in vitro differentiation of mDA neurons from stem cells, which are currently being developed for Parkinson's disease cell replacement therapy. Bone morphogenetic protein (BMP)/SMAD inhibition is routinely used during early steps of stem cell differentiation protocols, including for the generation of mDA neurons. However, the function of the BMP/SMAD pathway for in vivo specification of mammalian mDA neurons is virtually unknown. Here, we report that BMP5/7-deficient mice (Bmp5-/-; Bmp7-/-) lackmDAneurons due to reduced neurogenesis in the mDA progenitor domain. As molecular mechanisms accounting for these alterations in Bmp5-/-; Bmp7-/- mutants, we have identified expression changes of the BMP/SMAD target genes MSX1/2 (msh homeobox 1/2) and SHH (sonic hedgehog). Conditionally inactivatingSMAD1in neural stem cells of mice in vivo (Smad1Nes) hampered the differentiation of progenitor cells intomDAneurons by preventing cell cycle exit, especially of TH+SOX6+ (tyrosine hydroxylase, SRY-box 6) and TH+GIRK2+ (potassium voltage-gated channel subfamily-J member-6) substantia nigra neurons. BMP5/7 robustly increased the in vitro differentiation of human induced pluripotent stem cells and induced neural stem cells to mDA neurons by up to threefold. In conclusion, we have identified BMP/SMAD signaling as a novel critical pathway orchestrating essential steps of mammalian mDA neurogenesis in vivo that balances progenitor proliferation and differentiation. Moreover, we demonstrate the potential of BMPs to improve the generation of stem-cell-derived mDA neurons in vitro, highlighting the importance of sequential BMP/SMAD inhibition and activation in this process. [ABSTRACT FROM AUTHOR]

This study deals with the problem of reliable precise tracking control for the networked control system with non-zero external inputs (NEIs). A new control scheme is developed by introducing an integral item in the control law and taking stochastic actuator failure (SAF) into account, by which a better steady tracking performances can be achieved. Based on Lyapunov theory, a reliable control design method that guarantees the network-based tracking control systems with zero steady-state error in the conditions of both NEIs and SAFs is designed. Simulation results demonstrate the effectiveness of the developed controller design scheme. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the ability of axons to regenerate in injured spinal cord by activation of bone morphogenetic protein (BMP)/Smad1 signaling pathway in adult neurons. The study examined the expression patterns of Smad1 and performed injection of recombinant adeno-associated virus (AA) into the lumbar in adult mice. The study founds that BMP/Smad1 in axon outgrowth during development thus representing a therapeutic approach for axonal regeneration.