Numerical study of the applicability of the Saint-Venant principle

The limits of the applicability of the Saint-Venant principle are investigated while using the LIRA-CAD app. A large number of bars loaded at the end with different loads are considered. A graph of the distribution of the zones of influence of the Saint-Venant principle is plotted, depending on the size of the bars. It can be concluded that the stress-strain state near the perturbation zones can be represented by three components, two of which are linear, and the third is self-balanced in force and moment

Development of software based on spectral characteristics for wind load

A method is proposed for processing data from experimental or numerical simulation of wind loads and impacts in order to obtain spectral characteristics, which will make it possible to more correctly calculate the response of a structure, in particular, take into account the resonant and turbulent components that affect the stress-strain state of structures. In the Python programming language, the WIND SPECTRUM software module was written, designed to process simulation data based on spectral characteristics, which implements the developed technique. Examples of processing the wind effect obtained from the results of numerical simulation in the ANSYS CFX software package are also given

Itt1p, a novel protein inhibiting translation termination in Saccharomyces cerevisiae

BACKGROUND: Termination of translation in eukaryotes is controlled by two interacting polypeptide chain release factors, eRFl and eRF3. eRFl recognizes nonsense codons UAA, UAG and UGA, while eRF3 stimulates polypeptide release from the ribosome in a GTP- and eRFl – dependent manner. Recent studies has shown that proteins interacting with these release factors can modulate the efficiency of nonsense codon readthrough. RESULTS: We have isolated a nonessential yeast gene, which causes suppression of nonsense mutations, being in a multicopy state. This gene encodes a protein designated Itt1p, possessing a zinc finger domain characteristic of the TRIAD proteins of higher eukaryotes. Overexpression of Itt1p decreases the efficiency of translation termination, resulting in the readthrough of all three types of nonsense codons. Itt1p interacts in vitro with both eRFl and eRF3. Overexpression of eRFl, but not of eRF3, abolishes the nonsense suppressor effect of overexpressed Itt1p. CONCLUSIONS: The data obtained demonstrate that Itt1p can modulate the efficiency of translation termination in yeast. This protein possesses a zinc finger domain characteristic of the TRIAD proteins of higher eukaryotes, and this is a first observation of such protein being involved in translation

SMN Protein Can Be Reliably Measured in Whole Blood with an Electrochemiluminescence (ECL) Immunoassay: Implications for Clinical Trials

Spinal muscular atrophy (SMA) is caused by defects in the survival motor neuron 1 (SMN1) gene that encodes survival motor neuron (SMN) protein. The majority of therapeutic approaches currently in clinical development for SMA aim to increase SMN protein expression and there is a need for sensitive methods able to quantify increases in SMN protein levels in accessible tissues. We have developed a sensitive electrochemiluminescence (ECL)-based immunoassay for measuring SMN protein in whole blood with a minimum volume requirement of 5μL. The SMN-ECL immunoassay enables accurate measurement of SMN in whole blood and other tissues. Using the assay, we measured SMN protein in whole blood from SMA patients and healthy controls and found that SMN protein levels were associated with SMN2 copy number and were greater in SMA patients with 4 copies, relative to those with 2 and 3 copies. SMN protein levels did not vary significantly in healthy individuals over a four-week period and were not affected by circadian rhythms. Almost half of the SMN protein was found in platelets. We show that SMN protein levels in C/C-allele mice, which model a mild form of SMA, were high in neonatal stage, decreased in the first few weeks after birth, and then remained stable throughout the adult stage. Importantly, SMN protein levels in the CNS correlated with SMN levels measured in whole blood of the C/C-allele mice. These findings have implications for the measurement of SMN protein induction in whole blood in response to SMN-upregulating therapy

Evaluation of SMN Protein, Transcript, and Copy Number in the Biomarkers for Spinal Muscular Atrophy (BforSMA) Clinical Study

BACKGROUND: The universal presence of a gene (SMN2) nearly identical to the mutated SMN1 gene responsible for Spinal Muscular Atrophy (SMA) has proved an enticing incentive to therapeutics development. Early disappointments from putative SMN-enhancing agent clinical trials have increased interest in improving the assessment of SMN expression in blood as an early "biomarker" of treatment effect. METHODS: A cross-sectional, single visit, multi-center design assessed SMN transcript and protein in 108 SMA and 22 age and gender-matched healthy control subjects, while motor function was assessed by the Modified Hammersmith Functional Motor Scale (MHFMS). Enrollment selectively targeted a broad range of SMA subjects that would permit maximum power to distinguish the relative influence of SMN2 copy number, SMA type, present motor function, and age. RESULTS: SMN2 copy number and levels of full-length SMN2 transcripts correlated with SMA type, and like SMN protein levels, were lower in SMA subjects compared to controls. No measure of SMN expression correlated strongly with MHFMS. A key finding is that SMN2 copy number, levels of transcript and protein showed no correlation with each other. CONCLUSION: This is a prospective study that uses the most advanced techniques of SMN transcript and protein measurement in a large selectively-recruited cohort of individuals with SMA. There is a relationship between measures of SMN expression in blood and SMA type, but not a strong correlation to motor function as measured by the MHFMS. Low SMN transcript and protein levels in the SMA subjects relative to controls suggest that these measures of SMN in accessible tissues may be amenable to an "early look" for target engagement in clinical trials of putative SMN-enhancing agents. Full length SMN transcript abundance may provide insight into the molecular mechanism of phenotypic variation as a function of SMN2 copy number. TRIAL REGISTRY: Clinicaltrials.gov NCT00756821

The method of local impact for the analysis of structures for progressive collapse

A method for calculation on the progressive collapse, in accordance with which the account of the fall of ceiling panels on the underlying floor when the loss of bearing capacity of vertical frame elements in the form of local impact determined by multiplying the weight plates on the dynamic coefficient determined by the drop height and static deflection. The calculation is carried out in several stages with the use of the LIRA SAPR software

The study of the perturbation of normal stresses in the rod of the I-section in the zone of application of the load

The study of the implementation of the Saint-Venant principle for restrained rods of the I-section exposed to various loads at its free end is carried out. When using the program complex LIRA SAPR are defined zones of disturbance of normal stresses

Numerical study of the applicability of the Saint-Venant principle

The limits of the applicability of the Saint-Venant principle are investigated while using the LIRA-CAD app. A large number of bars loaded at the end with different loads are considered. A graph of the distribution of the zones of influence of the Saint-Venant principle is plotted, depending on the size of the bars. It can be concluded that the stress-strain state near the perturbation zones can be represented by three components, two of which are linear, and the third is self-balanced in force and moment

The SMN complex, an assemblyosome of ribonucleoproteins

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