Normal Sections Research Articles

Cross-Section Stability and Design of Normal Strength and High Strength Steel I-Sections in Fire

The structural response and design of normal strength and high strength steel I-sections at elevated temperatures are investigated in this paper. The shell finite element models of steel I-section elements capable of replicating their behavior in fire are developed and validated against experimental results from the literature. The validated shell finite element models are then utilized to generate extensive structural performance data for steel I-sections, considering a broad range of plate slenderness values for cross-section elements, elevated temperature levels, cross-section aspect ratios as well as different loading conditions and normal strength and high strength steel grades. The accuracy of the existing methods provided in the European structural steel fire design standard EN 1993-1-2 and its upcoming version prEN 1993-1-2 for the ultimate strength predictions of normal strength and high strength steel cross-sections in fire is assessed. Scope for improvement is observed. Considering this, a new method for the ultimate strength predictions of normal strength and high strength steel sections at elevated temperatures is put forward. It is shown that the proposed method leads to more accurate ultimate strength predictions for normal strength and high strength steel I-sections in fire with a higher level of reliability relative to the existing design methods provided in EN 1993-1-2 and prEN 1993-1-2.

P383 THIRD–DEGREE ATRIOVENTRICULAR BLOCK AND HYPERCALCEMIA: NOT ALWAYS JUST THE HEART

Abstract A 81–year–old lady was admitted to the ER due to anorexia, fever and oliguria. Previous medical history was unknown as she had arrived in Italy one month before and her son was not aware of it. Upon arrival she was soporous and bradicardic. Physical examination consisted of mild pulmonary rales, diffuse abdominal pain and leg edema. ECG showed a third–degree atrioventricular block with narrow QRS and average heart rate of 40 bpm with no signs of ischemia. X–ray showed mild congestion. She was admitted to CCU. Blood tests showed hypoglicemia (53 mg/dL), anemia (Hb 9.9g/dL), low platelet count, renal dysfunction (creatinine 1.43mg/dL), high C–reactive protein, normal potassium but high calcemia (13 mg/dL). To investigate hypercalcemia parathyroid hormone was dosed and was in range, so a CT scan was needed to rule out pancreatitis, cancer or bone lesions. Also a cardiac echo was done: it showed a hypertrophic left ventricle with preserved contractility, no significant valvular dysfunctions, normal right sections with pulmonary hypertension, no pericardial effusion. While performing the subcostal view however multiple formations were seen at the hepatic level. CT scan confirmed multiple pathological conglomerating lymphadenopathies in the abdomen towards the femoral region, reaching 5 cm of diameter; no bone lesions were found. Inguinal lymph node biopsy was performed. Due to persistent complete AV block along with persistent hypercalcemia and hypoglycemia despite medical therapy, considering the electrolyte imbalance not corrigible due to a malignancy a pacemaker was implanted. The result of the lymph node biopsy was consistent with a form of Diffuse Large B–Cell Lymphoma. This case highlights how a 3–rd degree AV block may present with non–specific symptoms. When it is found it may not always represent a pure cardiac problem as sometimes it is the epiphenomenon of a systemic disease. Particularity of this case is that cardiologists are less used to take into consideration calcium balance. Nevertheless, although infrequent, hypercalcemia is a cause of significant conduction disease. After having looked for it, searching for its etiology is mandatory as some could be reversible and thus the AV block as well. For this reason, when a complete AV block is found ruling out hypercalcemia is fundamental, taking into consideration that the conduction disease may represent the first red flag of an unknown malignancy

Spatial Whole Transcriptome Profiling of the Tumor Microenvironment in Prostate Carcinomas

BackgroundDespite years of studies and effort, the best strategies for treating prostate cancer and minimizing the complications of treatment remain unanswered questions. This gap in knowledge is partially due to the inability to dissect the complex heterogeneous tumor microenvironment (TME) and immune compartment. Spatially resolved molecular profiling of tumor sections will enhance our understanding of these complexities; However, it has been particularly challenging to do spatial molecular profiling in formalin‐fixed paraffin‐embedded (FFPE) tissues due to RNA degradation associated with this tissue‐embedding method, which is routinely used in oncology workflows.The 10x Genomics Visium Spatial Gene Expression Solution for FFPE tissue overcomes these limitations, enabling spatial gene expression analysis of FFPE tissues combined with classical histology staining techniques such as Hematoxylin & Eosin (H&E) staining and immunofluorescence.MethodsWe used the 10x Genomics Visium Spatial Gene Expression Solution for FFPE tissue to analyze and resolve tumorigenic profiles in sections of normal and adenocarcinoma prostate samples. This assay incorporates ~5,000 molecularly barcoded, spatially encoded capture probes in spots over which the tissue is placed, imaged, and permeabilized. Imaging and sequencing data are processed together, resulting in a spatially resolved transcriptional readout.ResultsWe profiled the whole transcriptome in normal, invasive adenocarcinoma, and acinar cell carcinoma FFPE human prostate tissues.Unsupervised clustering of the whole transcriptome data from normal, invasive adenocarcinoma, and acinar cell prostate carcinoma FFPE sections enabled the identification of 2 different regions, which had a well defined spatial distribution within the tissues. Well known prostate gland and prostate‐cancer markers were over‐expressed in the corresponding healthy and cancerous portions of the tissue, validating the performance of this method. We found that, while in healthy tissues basal cells and luminal cells are spatially organized, this pattern is lost in tumor samples, where luminal cells are greatly expanded in the invasive carcinoma region and do not colocalize with basal cells. Moreover, T lymphocytes are dispersed throughout the whole tissue section in the adenocarcinoma, while plasma B cells are located in the peritumoral region which could impact prognosis.ConclusionsSpatial whole transcriptome analysis opens new opportunities for better understanding the TME which can not only help discover novel predictive tumor biomarkers, but also enable identifying cell type and tumor region specific drug targets.

Harmonic unit normal sections of Grassmannians associated with cross products

Let $$G\left( k,n\right) $$ be the Grassmannian of oriented subspaces of dimension k of $$\mathbb {R}^{n}$$ with its canonical Riemannian metric. We study the energy of maps assigning to each $$P\in G\left( k,n\right) $$ a unit vector normal to P. They are sections of a sphere bundle $$E_{k,n}^{1}$$ over $$G\left( k,n\right) $$ . The octonionic double and triple cross products induce in a natural way such sections for $$k=2$$ , $$n=7$$ and $$k=3$$ , $$n=8$$ , respectively. We prove that they are harmonic maps into $$E_{k,n}^{1}$$ endowed with the Sasaki metric. This, together with the well-known result that Hopf vector fields on odd dimensional spheres are harmonic maps into their unit tangent bundles, allows us to conclude that all unit normal sections of the Grassmannians associated with cross products are harmonic. In a second instance we analyze the energy of maps assigning an orthogonal complex structure $$J\left( P\right) $$ on $$P^{\bot }$$ to each $$P\in G\left( 2,8\right) $$ . We prove that the one induced by the octonionic triple product is a harmonic map into a suitable sphere bundle over $$G\left( 2,8\right) $$ . This generalizes the harmonicity of the canonical almost complex structure of $$S^{6}$$ .

EARTH SECTION PATHS. SOLUTION TO THE INVERSE AND DIRECT PROBLEMS, AND WAYPOINTS WITHOUT ITERATIONS

The use of central elliptical sections in the calculation of air and sea routes and normal sections in Geodesy is common. Elliptic sections do not represent the shortest path between two points, although are often used in navigation to replace the geodesic lines. All developments include some kind of iteration to solve one of the problems, direct or inverse. When using vector algebra methods and perturbed series, the problems can be solved using an equidistant circle that represents the path of the elliptical section. This is possible because the flattening of the elliptical section is less than or equal to the Earth’s flattening, which implies that the series calculated for the terrestrial ellipsoid, used in the section, always converge. Three direct methods are described in order to calculate: the distance, the azimuth, the coordinates of a point and intermediate positions of an elliptical section. Those algorithms provide solutions to the inverse and direct algorithms with a consistency of the order of truncation error of double-type numbers.

Self-organization of magma supply controls crustal thickness variation and tectonic pattern along melt-poor mid-ocean ridges

In nature, variations in mantle sources and magmatic processes lead to significant changes of crustal thickness distribution and spreading pattern at mid-ocean ridges. Distributions in crust thicknesses are relatively uniform at fast ridges. On the contrary, great lateral fluctuations with even mantle rocks exhumation are observed at slow and ultraslow ridges. Similarity, the spreading pattern changes from symmetric configuration (at fast ridges) to highly asymmetric plates accretion with detachment faults and oceanic core complexes (at slow ridges). Recent modeling studies suggested that magmatism may play a key role in the variation. Yet, the physical mechanisms controlling spatial-temporal distribution and intensity of the magmatic activity at mid-ocean ridges remain elusive. In this study, using 3D self-consistent magmatic-thermomechanical numerical models, we systematically investigate the effect of mantle potential temperature and spreading rate on the crustal thickness lateral variations and tectonic pattern at spreading ridges of various opening rates. Our numerical results show that along melt-poor slow-ultraslow mid-ocean ridges, there are two fundamentally different types of ridge sections that spontaneously form and alternate. This is due to a tectono-magmatic instability which self-consistently partitions melt supply beneath the ridge. Two geometries form: (1) normal ridge sections (NR) with elevated topography, normal thickness of oceanic crust and a hot thermal structure, and (2) fracture zone sections (FZ) with lowered topography, thin/absent crust, exhumed mantle rocks, and a cold thermal structure. The tectono-magmatic instability along spreading ridges is triggered by the combined effects of a reduced melt supply from the mantle into crustal magma chambers and an increase in brittle layer thickness. Such bimodal structure is then maintained by the combined effects of buoyant melt partitioning along the ridge, localized latent heat release from crustal magma crystallization, and different spreading modes. This results, on one hand, in hotter, thinner and elevated magmatic sections (tectono-magmatic spreading), and, on the other hand, in colder, thicker and subsided amagmatic sections (purely tectonic spreading). This predicted bimodal distribution finds a good agreement with natural observations. This suggests that spontaneous self-organization of magma supply controlled by spreading rate and mantle potential temperature plays a critical role in shaping tectonic and crustal patterns of mid-ocean ridges.

Digital spatial profiling of collapsing glomerulopathy

Collapsing glomerulopathy is a histologically distinct variant of focal and segmental glomerulosclerosis that presents with heavy proteinuria and portends a poor prognosis. Collapsing glomerulopathy can be triggered by viral infections such as HIV or SARS-CoV-2. Transcriptional profiling of collapsing glomerulopathy lesions is difficult since only a few glomeruli may exhibit this histology within a kidney biopsy and the mechanisms driving this heterogeneity are unknown. Therefore, we used recently developed digital spatial profiling (DSP) technology which permits quantification of mRNA at the level of individual glomeruli. Using DSP, we profiled 1,852 transcripts in glomeruli isolated from formalin fixed paraffin embedded sections from HIV or SARS-CoV-2-infected patients with biopsy-confirmed collapsing glomerulopathy and used normal biopsy sections as controls. Even though glomeruli with collapsing features appeared histologically similar across both groups of patients by light microscopy, the increased resolution of DSP uncovered intra- and inter-patient heterogeneity in glomerular transcriptional profiles that were missed in early laser capture microdissection studies of pooled glomeruli. Focused validation using immunohistochemistry and RNA in situ hybridization showed good concordance with DSP results. Thus, DSP represents a powerful method to dissect transcriptional programs of pathologically discernible kidney lesions.

T-Cadherin, E-Cadherin, PR-A, and ER-α Levels in Deep Infiltrating Endometriosis.

The goal of this study was to compare the T-cadherin, E-cadherin, progesterone receptor (PR), and estrogen receptor (ER) staining levels of deep infiltrating endometriosis (DIE) tissue, ovarian endometriomas and normal endometrial tissues in the same individuals. The tissue sections of both DIE nodule(s) and endometrioma(s) of 15 cases were examined. As a control group, normal endometrial tissue sections of 23 cases were examined. T-cadherin, E-cadherin, ER-α, and PR-A staining levels of DIE, endometrioma tissues, and endometrial tissues were compared immunohistochemically. H -score was calculated to compare the expression of T-cadherin, E-cadherin, ER-α, and PR-A in immunohistochemical staining based on the percentage of cells stained at each intensity level. T-cadherin, E-cadherin, ER, and PR H -score were lowest in DIE tissue and highest in endometrial tissue ( P <0.0001, <0.0001, <0.0001, and <0.0001, respectively). In correlation analysis, a positive correlation was found between T-cadherin, E-cadherin, PR, and ER H -score ( P <0.0001 for each). T-cadherin, E-cadherin, ER, and PR H -score were lowest in DIE tissue and highest in endometrium tissue. We think that examination of DIE tissue and endometrioma tissue from the same individual excludes the possibility of an effect due to different genetic and environmental factors from different individuals. With the help of this exclusion we showed that DIE and endometrioma have different biological properties.

Evaluation of Sodium Valproate-Induced Hepatotoxicity and Protective Role of Vitamin C (Ascorbic Acid) and Silymarin in Adult Albino Rats

Background and Objectives: Drugs hepatotoxicity is one of the most prevalent problems seen in medical practice. Many medications are linked to hepatotoxicity, including acetaminophen, tamoxifen and sodium valproate (VPA). The objective of this study is to investigate the preventive impact of silymarin (SIL) and /or vitamin C (Vit.C) on hepatotoxic Sodium Valproate in albino Rats. &#x0D; Methods: Thirty adult male albino rats were divided equally into six groups; group (I): normal control, group (II): VPA 700 mg/kg, group (III): VPA + SIL 50 mg/kg, group (IV): VPA+ Vit.C 50 mg/kg and group (VI): VPA + SIL +Vit.C, VPA. The animals were killed after 14 days, and livers were taken for histological and biochemical analysis.&#x0D; Results: After 14 days, animals were sacrificed, and livers were collected for histopathologic examination and biochemical assessment. VPA group exhibited a significant increase in serum alanine aminotransferase and aspartate aminotransferase. Liver sections showed loss of normal pattern of hepatocytes, inflammatory infiltration, congested central vein and fatty infiltration. Each of ascorbic acid and silymarin partially improved the histological pattern of the liver. When they were combined together, they depict marked improvement in the measured parameters and showed normal liver sections.&#x0D; Conclusion: silymarin (SIL) and /or vitamin C (Vit.C) has hepatoprotective effects against VPA induced toxicity on liver.

Несуча здатність доведених до граничного стану (ULS) пошкоджених бетонних балок з ВFRP, підсилених фіброармованими пластиками (СFRP)

The aim of this article is to familiarize with the experimental and theoretical study of the load-bearing capacity of BFRP concrete beams damaged in previous studies and brought to failure, reinforced with carbon-plastic fabric in the lower stretched zone and carbon-plastic jackets in the supporting areas under the action of low-cycle sign-repeated transverse loading of high levels with the development of initial data for the physical model of the methodology for calculating the strength of their normal and inclined sections. The article presents the results of testing concrete beams reinforced with ВFRP, strengthened with carbon fiber reinforced polymer (CFRP) strips in the lower tensile zones and carbon fiber reinforced polymer jackets at support sections, previously tested to ultimate limit state (ULS). The load-carrying capacity of the reinforced FRP support sections of beam structures, brought to the ultimate limit state (ULS), should be determined primarily under the action of bending moment through the critical inclined crack. The performed experimental and theoretical studies have established the possibility and feasibility of strengthening damaged and brought to the boundary state (ULS) concrete structures with BFRP external fiber-reinforced plastics (CFRP) while observing the established technology. The bearing capacity of CFRP-reinforced damaged concrete beams with BFRP should only be determined for the action of bending moments along normal sections in elements with large (a/d = 3) and medium (a/d = 2) shear spans and along inclined sections in beams with small (a/d=1) shear spans.

Evaluation of travel time reliability in urban areas using mobile navigation applications in Jordan

This study aims to assess the Travel Time Reliability (TTR) in urban areas in Irbid city, Jordan, using a mobile application (Ultra GPS Logger), which retains the current location, speed, and time every three seconds. The study evaluated the TTR at the Origin-Destination (OD) level and the segment level. Each OD was divided into several segments with different interruption types to determine which segments have the lowest reliability and the most extended delay. The evaluation was based on several measures according to the Federal Highway Administration (FHWA), such as the buffer time, Buffer Index (BI), Travel Time Index (TTI), 95th percentile, standard deviation, and Coefficient of Variation. Chi-Square test for independence was carried to study the association between the period during the day, day of the week, and section type with the BI Level, and other combinations. Results showed that the normal sections, without traffic signals and roundabouts, had a significant effect on TTR compared with 3-Leg intersections, 4-Leg intersections, and roundabouts. Results also confirmed that trips reliability does not mean there is no delay or congestion, but there is some certainty in travel time prediction for a specific route and journey.

Research on Surrounding Rock Stability Test of Tunneling Roadway under Complex Geological Conditions

Different geological conditions are often encountered in the excavation of coal mine roadways, with fault-fracture zone being the most commonly seen complex geological conditions. Fault-fracture zone is characterized by complex lithologic property and joint development and can easily cause safety accidents when excavation burrows through the fault. Therefore, grouting reinforcement of fault-fracture zone is often implemented to ensure coal mine safety production. Based on the tunnel excavation case of −530 - −650 m belt conveyor inclined roadway at Huainan Pan’er Coal Mine, borehole optical fiber and electrical testing technologies were applied to monitor and analyze the dynamics of the surrounding rock stability when roadway excavation passed through the F1 fault, and evaluate the effect of grouting reinforcement on fault-fracture zone. According to the results of optical fiber and electrical methods, the distributional characteristics and evolution patterns of strain and electric resistivity were analyzed. The research pointed out the distinct difference in variation characteristics of strain and electrical fields between grouted reinforced fault-fracture zone and normal rock strata sections. This indicates that the grouting reinforcement effectively improve physical properties of rock strata in the fractured section, the stability of the rock strata at the fault-fracture zone was effectively increased, the degree of fault activation and deformation was relatively small, and roadway surrounding rock basically retained its original properties, pointing to high stability.

EVALUATION OF NLRP3 INFLAMMASOME PROTEIN EXPRESSION IN ULCERATIVE COLITIS

The aim: This study aimed to evaluate the NLRP3 immunoreactivity in ulcerative colitis in various clinical presentations. Materials and methods: The retrospective study involved 80 formalin fixed paraffin embedded tissue blocks. These were divided into 50 samples of ulcerative colitis and 30 with normal colonoscopy findings. NLRP3 protein expression patterns were evaluated in various cellular components in tissue sections using immunohistochemistry method. Results: NLRP3 inflammasome was significantly expressed with higher percentage among ulcerative colitis tissue sections compared with normal tissue sections. Intense staining was observed in Paneth cells at the base of crypts, inflammatory cells infiltrated between glands and near the base of crypts. Variable intensities of NLRP3 staining were observed in surface epithelial cells and glandular epithelium. Statically higher percentage of expression was found among active disease and patients with extra-intestinal complications. Conclusions: The NLRP3 protein expression pattern was upregulated among various cellular compartments among ulcerative colitis and correlated with disease activity.

ЧИСЛЕННО-ЭКСПЕРИМЕНТАЛЬНОЕ ИССЛЕДОВАНИЕ НЕЛИНЕЙНОГО СЖАТИЯ ПАКЕТОВ МЕТАЛЛИЧЕСКИХ ПЛЕТЕНЫХ СЕТОК

The results of numerical simulation of elastoplastic compression of symmetrical fragments of a package of woven steel meshes are presented. The thickness of the symmetrical fragment is one and two layers. The study was carried out under dynamic loading conditions in the ANSYS LS-DYNA computer system. The mesh package is formed by superimposing layers on top of each other while maintaining the direction of the wires. The packet has a quasi-periodic structure; therefore, symmetrical fragments can be distinguished. For two mesh layers, a fragment is accepted, taking into account the shift of the layer in the lateral directions by half the size of the cell. The compression was carried out by a pair of absolutely rigid plates moving symmetrically towards each other at a constant speed for a given time interval. A multilinear plasticity model with isotropic hardening was used to describe the behavior of the material. If the maximum specified deformation is exceeded in the calculation, the diagram automatically continues with a small linear hardening modulus. A comparative analysis of numerical solutions for the compression of symmetrical fragments from one and two layers of a woven mesh is carried out. When the fragments are compressed, a strongly uneven stress-strain state arises in the wires, especially large irreversible deformations occur in the knots of weaving. The deformation curves of the fragments have characteristic inflections associated with the fact that the deformation process includes not only knots of weaving, but also deformations of wire compression along its entire length. The numerical results are compared with the experimental dynamic compression curve of a multilayer mesh package. The compression curves are different for one and two layers. For two layers of grids, the deformation curve at low pressure is more consistent with the experimental data. Two stages of behavior of the deformation diagram are observed at low and high degrees of compression, the characteristic inflection is formed somewhat earlier than in the numerical solution for one layer. Numerical dependences of the relative area of the normal and lateral passage sections of a symmetrical fragment of a mesh package on the compression strain are obtained. These data can be used to simulate the propagation of shock waves through multilayer woven mesh packages.

Immunohistochemical expression of cyclooxygenase-2 in oral lichen planus and normal oral mucosa

Oral lichen planus (OLP) is a chronic inflammatory disease for which the pathogenesis is complex and not fully understood; autoimmunity has been suggested as a causative factor. World health organization (WHO) has classified OLP as a potentially malignant lesion. Cyclooxygenase-2 (COX-2) is an inducible key enzyme that generates prostanoids which play a critical role in inflammation, immunopathology; also considered as a malignant potential marker. The present study was conducted to analyze and compare epithelial COX-2 expression in OLP clinical subtypes and normal oral mucosa to evaluate its role in the pathophysiology of the disease process. This retrospective immunohistochemistry (IHC) study was performed on tissue sections of 30 OLP and 10 normal oral mucosae for COX-2 expression. Descriptive and comparative statistical methods were done using 'one-way Analysis of Variance (ANOVA), 't' and Chi-square tests. All the OLP showed epithelial COX-2 expression; strong expression was noted in 80% of the OLP while normal oral mucosa sections showed no expression. Cox-2 expression was significantly higher in erosive lichen planus compared to reticular lichen planus. Strong expression of COX-2 in OLP suggested its important role in pathogenesis. Although COX-2 has been connected to malignant development and autoimmunity, as the malignant development in OLP is quite rare, this study suggests that increased levels of COX-2 seen here may support an autoimmune cause of the disease process.

Анализ результатов расчета железобетонных плит с дисперсным армированием при упругой и неупругой работе нормальных сечений

The article provides an analysis of the calculation results of reinforced concrete slabs with dispersed reinforcement for elastic and inelastic operation of normal sections and various forms of stress diagrams. These materials include classical reinforced cement (the bar diameter is 1.2 mm with a pitch of 10 mm) and its variant, heavy reinforced cement (the bar diameter is 3-5 mm with a pitch of 15-30 mm). Reinforcement is applied evenly over the entire thickness. There has been found out that during elastic operation of sections and triangular stress diagrams, the calculated bearing capacity of the slabs is determined by the concrete strength in the compressed zone, and it is much lower than the actual one. In the plastic operation of sections and with rectangular stress diagrams, the design bearing capacity exceeds the actual one averagely up to15 %.The calculated bearing capacity of plates with dispersed reinforcement is recommended to be determined with parabolic stress diagrams.

Features of the Calculation of Bending Elements of Steel-Fiber-Concrete Structures According to Normal Sections

Features of the Calculation of Bending Elements of Steel-Fiber-Concrete Structures According to Normal Sections

ПРОЧНОСТЬ СЖАТЫХ И ВНЕЦЕНТРЕННО СЖАТЫХ ЖЕЛЕЗОБЕТОННЫХ ЭЛЕМЕНТОВ С ЗОННЫМ АРМИРОВАНИЕМ ИЗ СТАЛЬНОЙ ФИБРЫ

The real nonlinear diagrams of concrete, reinforcement and steel-fiber concrete under dynamic loading are formulated and analytically described. Theoretical and experimental studies of the operation of compressed and non-centrally compressed elements with different levels of load application eccentricity under static and short-term dynamic loads are carried out. 3 reinforced concrete and 9 steel-fiber concrete elements were manufactured and tested for short-term dynamic load under central and off-center compression. New experimental data characterizing the process of deformation and destruction of steel-reinforced concrete models of columns have been obtained. Also, the schemes of destruction and cracking, the dependence of changes in the dynamic load over time, the movement of concrete, reinforcement and steel-fiber concrete over time are obtained. A method has been developed for calculating the strength and stability of such elements, taking into account the reinforcement of the section with steel fiber concrete. The influence of the use of zone reinforcement with steel fiber of compressed and non-centrally compressed reinforced concrete elements is numerically analyzed. The results of the calculation according to the developed methodology are compared with the results of experimental data. The optimal variant of the application of zone reinforcement made of steel fiber for compressed and non-centrally compressed elements operating under static and short-term dynamic loads is proposed. The analysis of the calculation results based on the developed method for calculating the strength of normal sections of non-centrally compressed reinforced concrete and steel-fiber concrete, based on the deformation model, and their comparison with the data of experimental studies under short-term dynamic loading show that the deviations are on average 10-18 %, which indicates that the developed method has sufficient accuracy to solve practical problems.

The Different Immune Profiles of Normal Colonic Mucosa in Cancer-Free Lynch Syndrome Carriers and Lynch Syndrome Colorectal Cancer Patients

Owing to the high load of immunogenic frameshift neoantigens, tumors arising in individuals with Lynch syndrome (LS), the most common inherited colorectal cancer (CRC) syndrome, are characterized by a pronounced immune infiltration. However, the immune status of normal colorectal mucosa in LS is not well characterized. We assessed the immune infiltrate in tumor-distant normal colorectal mucosa from LS CRC patients, sporadic microsatellite-unstable (MSI) and microsatellite-stable (MSS) CRC patients, and cancer-free LS carriers. CD3-positive, FOXP3-positive, and CD8-positive T cells were quantified in, respectively, 219, 233, and 201 formalin-fixed paraffin-embedded (FFPE) normal colonic mucosa tissue sections from CRC patients and cancer-free LS carriers and 26, 22, and 19 LS CRCs. CD3-positive T cells were also quantified in an independent cohort of 97 FFPE normal rectal mucosa tissue sections from LS carriers enrolled in the CAPP2 clinical trial. The expression of 770 immune-relevant genes was analyzed in a subset of samples with the use of the NanoString nCounter platform. LS normal mucosa specimens showed significantly elevated CD3-, FOXP3-, and CD8-positive T-cell densities compared with non-LS control specimens. Gene expression profiling and cluster analysis revealed distinct immune profiles in LS carrier mucosa with and without cancer manifestation. Long-term follow-up of LS carriers within the CAPP2 trial found a correlation between mucosal T-cell infiltrate and time to subsequent tumor occurrence. LS carriers show elevated mucosal T-cell infiltration even in the absence of cancer. The normal mucosa immune profile may be a temporary or permanent tumor risk modifier in LS carriers.

Epigenetic imprinting alterations as effective diagnostic biomarkers for early-stage lung cancer and small pulmonary nodules

BackgroundEarly lung cancer detection remains a clinical challenge for standard diagnostic biopsies due to insufficient tumor morphological evidence. As epigenetic alterations precede morphological changes, expression alterations of certain imprinted genes could serve as actionable diagnostic biomarkers for malignant lung lesions.ResultsUsing the previously established quantitative chromogenic imprinted gene in situ hybridization (QCIGISH) method, elevated aberrant allelic expression of imprinted genes GNAS, GRB10, SNRPN and HM13 was observed in lung cancers over benign lesions and normal controls, which were pathologically confirmed among histologically stained normal, paracancerous and malignant tissue sections. Based on the differential imprinting signatures, a diagnostic grading model was built on 246 formalin-fixed and paraffin-embedded (FFPE) surgically resected lung tissue specimens, tested against 30 lung cytology and small biopsy specimens, and blindly validated in an independent cohort of 155 patients. The QCIGISH diagnostic model demonstrated 99.1% sensitivity (95% CI 97.5–100.0%) and 92.1% specificity (95% CI 83.5–100.0%) in the blinded validation set. Of particular importance, QCIGISH achieved 97.1% sensitivity (95% CI 91.6–100.0%) for carcinoma in situ to stage IB cancers with 100% sensitivity and 91.7% specificity (95% CI 76.0–100.0%) noted for pulmonary nodules with diameters ≤ 2 cm.ConclusionsOur findings demonstrated the diagnostic value of epigenetic imprinting alterations as highly accurate translational biomarkers for a more definitive diagnosis of suspicious lung lesions.