This paper aims to investigate the performance of typical cold-formed steel (CFS) beam-to-beam connections between floor bearers and floor joists through a series of full-scale experiments. The investigated connections consisted of a lipped channel (floor joist), an unlipped channel (floor bearer), a thin-walled clip angle (connector), and a self-drilling screw (fastener). In this study, customised T-shaped and H-shaped CFS connection specimens were tested to examine the performance under tension and shear loads, respectively. Two sizes of self-drilling screws, 10 G and 14 G, were used with the selected load bearing clip angle. The fabricated connection specimens were subjected to displacement-controlled tension and shear loads. The experiments uncovered the ultimate connection strengths, load-displacement relationships, and failure mechanisms of the designed CFS connections under the applied loads. Moreover, the experimental tensile and shear strengths of the connections were compared with the strengths predicted by the standard design equations. It was found that the screw pullout on the anchored leg of the clip angle was the main mode of failure under the tensile load. On the other hand, two different failure modes—fracturing of 10 G screws or shear buckling of the cantilevered leg of the clip angle with 14 G screws—were observed in the H-shaped specimen under the applied shear load. Among the designed connection specimens, the maximum tensile load capacity was 30.86 kN and the maximum shear load capacity 88.15 kN. The standard design calculations predicted screw pullout failure under tension, while the shear bucking failure mode of the clip angle under shear load was overlooked.
Poly(ADP-ribose) polymerase (PARP) is a critical DNA repair enzyme involved in DNA single-strand break repair via the base excision repair pathway. PARP inhibitors have been shown to sensitize tumors to DNA-damaging agents and to also selectively kill homologous recombination repair-defective cancers, such as those arising in BRCA1 and BRCA2 mutation carriers. Recent proof-of-concept clinical studies have demonstrated the safety and substantial antitumor activity of the PARP inhibitor, olaparib in BRCA1/2 mutation carriers, highlighting the wide therapeutic window that can be achieved with this synthetic lethal strategy. Likewise, the PARP inhibitor, BSI-201, in combination with carboplatin and gemcitabine have produced promising results in "triple-negative" breast cancers. There are also currently numerous other PARP inhibitors in clinical development. The potential broader therapeutic application of these approaches to a wide range of sporadic tumors harboring specific defects in the homologous recombination repair pathway has generated a great deal of excitement within the oncology community. This review discusses the rationale for targeting PARP and details the strategies and challenges involved in the clinical development of such inhibitors and their future potential applications in cancer medicine.
Dormancy-associated antigens encoded by the dormancy survival regulon (DosR) genes are required for survival of Mycobacterium tuberculosis (Mtb) in macrophages. However, mechanisms underlying survival of Mtb in macrophages remains to be elucidated. A recombinant Mycobacterium smegmatis strain (rMs) expressing a fusion protein of two dormancy‑associated antigens Rv2031c and Rv2626c from Mtb was constructed in the present study. In an in vitro culture, growth rate of rMs was lower compared with Ms. A total of 24 h following infection of murine macrophages with rMs or Ms, percentage of viable cells decreased and the number of bacteria in viable cells increased compared with Ms, demonstrating that virulence and intracellular survival of rMs were enhanced. Compared with macrophages infected with Ms, necrosis of macrophages infected with rMs was increased, while apoptosis was inhibited. Macrophages infected with rMs secreted more interferon‑γ and interleukin‑6, but fewer nitric oxide and tumor necrosis factor‑α, compared with macrophages infected with Ms. The present study demonstrated that the fusion protein composed of dormancy‑associated antigens Rv2031c and Rv2626c in Ms serves a physiological function of a dormancy‑associated antigen and modulates innate immunity of host macrophages, therefore favoring intracellular bacillary survival.
