The effect of geometrical presplit blast parameters on presplit quality at Kuusilampi open pit mine

In open pit mines, controlled blasting methods are used to reduce blast damage on the remaining rock mass, which increases the safety and economy of the operation. Presplitting is one of the most common controlled blasting methods used to achieve stable pit walls. The aim of this thesis is to discover suitable presplitting designs for the different areas of the Kuusilampi open pit mine. Furthermore, this thesis studied the connection between a geotechnical block model's rock mass quality estimates and the result of presplit blasting. This study has been conducted to improve the slope stability at the mine by improving the presplit blasting practices. This thesis consists of a historical review of presplitting practice at Kuusilampi open pit and presplitting tests. Presplitting tests were conducted with smaller diameter explosive cartridge than previously used and different borehole diameters, inclinations and spacings. The results were estimated based on visual inspection of the presplit faces and by calculating the half core factor, and over- and underbreak in cubic meters per square meter of presplit face. In this thesis, no major differences were found in the presplit results with the different presplit parameters. Furthermore, it was concluded that the greatest improvements to the slope stability at the Kuusilampi open pit could be achieved with modifications to the buffer row. Additionally, no connection was found between the rock mass quality estimate of the geotechnical block model and presplitting results, because the geotechnical block model was found to lack sufficient accuracy and resolution to represent the rock mass quality accurately

Physiological levels of estradiol limit murine osteoarthritis progression

Among patients with knee osteoarthritis (OA), postmenopausal women are over-represented. The purpose of this study was to determine whether deficiency of female sex steroids affects OA progression and to evaluate the protective effect of treatment with a physiological dose of 17β-estradiol (E2) on OA progression using a murine model. Ovariectomy (OVX) of female mice was used to mimic a postmenopausal state. OVX or sham-operated mice underwent surgery for destabilization of the medial meniscus (DMM) to induce OA. E2 was administered in a pulsed manner for 2 and 8 weeks. OVX of OA mice did not influence the cartilage phenotype or synovial thickness, while both cortical and trabecular subchondral bone mineral density (BMD) decreased after OVX compared with sham-operated mice at 8 weeks post-DMM surgery. Additionally, OVX mice displayed decreased motor activity, reduced threshold of pain sensitivity, and increased number of T cells in the inguinal lymph nodes compared to sham-operated mice 2 weeks after OA induction. Eight weeks of treatment with E2 prevented cartilage damage and thickening of the synovium in OVX OA mice. The motor activity was improved after E2 replacement at the 2 weeks time point, which was also associated with lower pain sensitivity in the OA paw. E2 treatment protected against OVX-induced loss of subchondral trabecular bone. The number of T cells in the inguinal lymph nodes was reduced by E2 treatment after 8 weeks. This study demonstrates that treatment with a physiological dose of E2 exerts a protective role by reducing OA symptoms

Pulsed administration for physiological estrogen replacement in mice

Estrogens are important regulators of body physiology and have major effects on metabolism, bone, the immune- and central nervous systems. The specific mechanisms underlying the effects of estrogens on various cells, tissues and organs are unclear and mouse models constitute a powerful experimental tool to define the physiological and pathological properties of estrogens. Menopause can be mimicked in animal models by surgical removal of the ovaries and replacement therapy with 17β-estradiol in ovariectomized (OVX) mice is a common technique used to determine specific effects of the hormone. However, these studies are complicated by the non-monotonic dose-response of estradiol, when given as therapy. Increased knowledge of how to distribute estradiol in terms of solvent, dose, and administration frequency, is required in order to accurately mimic physiological conditions in studies where estradiol treatment is performed. In this study, mice were OVX and treated with physiological doses of 17β-estradiol-3-benzoate (E2) dissolved in miglyol or PBS. Subcutaneous injections were performed every 4 days to resemble the estrus cycle in mice. Results show that OVX induces an osteoporotic phenotype, fat accumulation and impairment of the locomotor ability, as expected. Pulsed administration of physiological doses of E2 dissolved in miglyol rescues the phenotypes induced by OVX. However, when E2 is dissolved in PBS the effects are less pronounced, possibly due to rapid wash out of the steroid. </p

Phosphorylation site S122 in estrogen receptor alpha has a tissue-dependent role in female mice

Estrogen treatment increases bone mass and reduces fat mass but is associated with adverse effects in postmenopausal women. Knowledge regarding tissue-specific estrogen signaling is important to aid the development of new tissue-specific treatments. We hypothesized that the posttranslational modification phosphorylation in estrogen receptor alpha (ER alpha) may modulate ER alpha activity in a tissue-dependent manner. Phosphorylation of site S122 in ER alpha has been shown in vitro to affect ER alpha activity, but the tissue-specific role in vivo is unknown. We herein developed and phenotyped a novel mouse model with a point mutation at the phosphorylation site 122 in ER alpha (S122A). Female S122A mice had increased fat mass and serum insulin levels but unchanged serum sex steroid levels, uterus weight, bone mass, thymus weight, and lymphocyte maturation compared to WT mice. In conclusion, phosphorylation site S122 in ER alpha has a tissue-dependent role with an impact specifically on fat mass in female mice. This study is the first to demonstrate in vivo that a phosphorylation site in a transactivation domain in a nuclear steroid receptor modulates the receptor activity in a tissue-dependent manner