Indeterminate reinforced concrete frames subjected to inelastic cyclic deformation.

Four full-size statically indeterminate reinforced concrete frames with two symmetrical bays were tested to obtain sufficient data to evaluate the adequacy of the current ACI-ASCE Committee 352 design recommendations, as well as to determine whether a relaxation of some of the limits in these guidelines can be justified. Each specimen contained three 8.5-foot-long columns, connected at mid-height by two 9-foot-long beams. Initially, a constant axial load was applied to each column. The specimens were then subjected to a displacement-controlled loading schedule to simulate the type of displacements a frame may experience during a severe earthquake. In designing the specimens, the latest recommendations of the ACI-ASCE Committee 352 and the ACI building code ACI 318-83 were satisfied except for the following modifications: (1) the flexural strength ratio (M(R)) in the second specimen was reduced from 1.4 to 1.2, (2) the shear-stress factors (γ) in the joints of the third specimen were increased from 12 and 15 to 15 and 20 for the exterior and interior joints respectively, and (3) the number of the transverse reinforcements inside the right exterior joint in the fourth specimen was reduced from 4 to 2 sets of hoops. The conclusion inferred from the results indicate that for drift levels within the elastic range, the elongations and the rotations of the beam regions near the faces of the columns, in addition to the joint shear strains, were not affected by the design values for the primary variables in the last three specimens. For larger excursions into the inelastic range, the relaxation of the current Committee 352 design recommendations in the last three specimens not only showed a significant effect in reducing the elongations and the rotations of the beams, or in increasing the joint shear strains but led to lower energy dissipation of the specimens. Consequently, the current design guidelines by the ACI-ASCE Committee 352 yield statically indeterminate frames which exhibit sufficient ductility

Identification of Novel Mutations in Colorectal Cancer Patients Using AmpliSeq Comprehensive Cancer Panel

Biomarker discovery would be an important tool in advancing and utilizing the concept of precision and personalized medicine in the clinic. Discovery of novel variants in local population provides confident targets for developing biomarkers for personalized medicine. We identified the need to generate high-quality sequencing data from local colorectal cancer patients and understand the pattern of occurrence of variants. In this report, we used archived samples from Saudi Arabia and used the AmpliSeq comprehensive cancer panel to identify novel somatic variants. We report a comprehensive analysis of next-generation sequencing results with a coverage of >300X. We identified 466 novel variants which were previously unreported in COSMIC and ICGC databases. We analyzed the genes associated with these variants in terms of their frequency of occurrence, probable pathogenicity, and clinicopathological features. Among pathogenic somatic variants, 174 were identified for the first time in the large intestine. APC, RET, and EGFR genes were most frequently mutated. A higher number of variants were identified in the left colon. Occurrence of variants in ERBB2 was significantly correlated with those of EGFR and ATR genes. Network analyses of the identified genes provide functional perspective of the identified genes and suggest affected pathways and probable biomarker candidates. This report lays the ground work for biomarker discovery and identification of driver gene mutations in local population

Clinico-Pathological Features and Immunohistochemical Comparison of p16, p53, and Ki-67 Expression in Muscle-Invasive and Non-Muscle-Invasive Conventional Urothelial Bladder Carcinoma

Introduction: The identification of bladder detrusor muscle invasion in urothelial cancer is essential for prognosis and management. We studied the clinical, histological, and immunohistochemical expression of p16, p53, and Ki-67 in urothelial detrusor muscle-invasive bladder cancer (MIBC) and urothelial non-detrusor muscle-invasive bladder cancer (NMIBC) in Egyptian patients. Methods: Sixty-two bladder urothelial cancer cases obtained through TURBT were included and divided into two groups: (MIBC, stage T2) and NMIBC (T1). Tissue blocks were recut and re-examined microscopically; then, the immunostaining of p16, p53, and Ki-67 was performed to compare both groups and evaluate the 13% cut-off for Ki-67, 20% for p53, and p16 intensity in various conditions aided by telepathology technology. Results and conclusion: Hematuria was the main clinical first presentation, with no significant difference between either group. The mean age was 61.6 years, with male predominance (52 males and 10 females). The absence of papillary histological pattern was associated with a higher stage, including detrusor muscle invasion (p = 0.000). The overall average percent of p53 immunostaining was 12.9%, revealing no significant difference between MIBC and NMIBC when a cut-off of 20% was implicated. The Ki-67 expression was correlated with higher grade and muscle invasion; however, no association was found with the other two markers’ expression. The negative immunostaining of p16 was associated with low grade and NMIBC in the case of the preservation of the papillary pattern. We recommend further studies on the cut-off of widely used markers and more immunohistochemical and genetic studies on the p16(INK4A), taking into consideration the histological pattern of conventional carcinomas