No abstract

No abstract

Insulin-like growth factor binding protein (IGFBP)-3 has been shown to potently inhibit proliferation of various cell types in an insulin-like growth factor (IGF)-independent manner. We have previously shown that IGFBP-3 induces apoptosis in an IGF-independent manner through the activation of caspases involved in a death receptor-mediated pathway in MCF-7 human breast cancer cells. In the present study, we present further evidence that IGFBP-3 inhibits cell proliferation through the induction of cell cycle arrest in the same cell line. Induction of IGFBP-3 in MCF-7 cells inhibited cell proliferation whereas presence of small interfering RNA against IGFBP-3 abolished cell inhibitory effect of IGFBP-3, suggesting that the observed growth inhibition is specific. Flow cytometry analysis showed that induced expression of IGFBP-3 led to an arrest of the cell cycle in G1-S phase. Western immunoblot analysis showed a significant decrease in the levels of the cell cycle-regulated proteins such as cyclin D1, cyclin D3, cyclin E, cyclin A, cyclin-dependent kinase (CDK) 2, CDK4, retinoblastoma protein (pRB), and phosph-pRB, suggesting a possible mechanism for cell cycle arrest by IGFBP-3. Northern blot analysis and real-time quantitative PCR demonstrated a significant decrease in gene expression of cyclin D1. Additional phosphorylation assay showed that IGFBP-3 decreased the phosphorylation activity of CDK2 and CDK4. These results show that cellular production of IGFBP-3 leads to G1 cell cycle arrest with inhibition of CDK2 and CDK4. Taken together, IGFBP-3 exerts its growth inhibitory action through not only induction of apoptosis but also the G1 cell cycle arrest in human breast cancer cells.

Abstract:In order to mitigate carbon dioxide (CO 2 ) emissions, policy action that addresses vehicle emissions is essential. While many previous studies have focused on light-duty vehicles (LDV), little is known about medium-and heavy-duty vehicles (MHDV). This study lays the groundwork for future MHDV investigations in the Republic of Korea by developing an MHDV CO 2 emissions inventory. The bottom-up approach was used to calculate national CO 2 emissions. Simulation methods that calculated the CO 2 emissions of each vehicle and statistical data, such as vehicle miles traveled (VMT) and the number of registered vehicles were used to predict CO 2 emissions. The validity of this simulation model was examined by comparing it with the chassis dynamometer test results. The results of this study showed that the CO 2 emissions of MHDV in 2015 were 24.47 million tons, which was 25.5% of the total road transportation CO 2 emissions, despite only comprising 4.2% of the total vehicles. Trucks emitted 69.6% and buses emitted 30.4% of the total MHDV CO 2 emissions. Using the results between 2012 and 2015, the level of business-as-usual (BAU) CO 2 emissions will be 25.37 million tons in 2020.

No abstract

2794 Background The main difference of recently developed new prognostic classification, EUTOS score, from the conventionally used Sokal and Hasford scores is the simplicity of adopting only 2 clinical parameters, basophil counts and size of spleen, to discriminate high vs. low risks in chronic myeloid leukemia (CML). Concerns may rise from possible inter-observer gap when measuring the size of spleen. While there is currently controversial debate on its prognostic power, we present our single center results of comparing EUTOS score with other two scores. Patients and Methods Among 380 adult patients, consecutively registered as early chronic phase (CP) CML at Seoul St. Mary's Hospital (Jan. 2004 – Apr. 2010), who received imatinib (IM) as frontline therapy, 255 were evaluable for analysis: subjects were strictly limited to those with documented clinical parameters measured at very early time of diagnosis by a single doctor, before any cytoreduction therapies. The median age was 42 years (range, 19–77) with a slight male predominance (57%). Cytogenetic and molecular responses were calculated at specific time points and cumulative rates of response were compared according to risk scores. Event-free survival (EFS) was analyzed by time from start of IM to the time of events, defined by death from any cause, primary or secondary resistance to IM, progression to advanced phases, intolerance to IM and switch to second line tyrosine kinase inhibitor (TKI) or allografting. Response assessment followed current European Leukemia Net recommendation. Results Median time from diagnosis to IM start was 14 days (range, 1–183). After a median follow-up duration of 56.6 months (range, 13.0–102.2) in survivors, there were 10 deaths and 3 patients with disease progression to accelerated phase of blastic crisis. Sixty-four patients had switched IM to second TKI due to either IM resistance or intolerance. Overall comparisons are described in Table 1. Of 42 EUTOS high risk patients, only 25 high risk patients by Sokal and 15 by Hasford were included. Almost 90% of either low or intermediate (INT) risk patients by all risk models achieved complete cytogenetic response (CCyR) at 12 months after IM, whereas high risk groups had lower rates, especially in EUTOS high risk (57%, p = <0.0001). Regarding major molecular response (MMR) at 18 months, significant differences were observed according to risk stratifications by Sokal and EUTOS, but not in Hasford risks, in which the same proportion of low and INT risks achieved MMR (48%, P = 0.308). This seemingly less prominent prognostic difference of low vs. INT groups of Sokal and Hasford scores were further demonstrated by insignificant difference between these groups in cumulative incidence (CI) of CCyR and MMR. All 3 high risk groups showed significantly lower incidence of both CCyR and MMR compared to low risk groups. INT risk groups by Sokal and Hasford models failed to show statistical significance in all three outcomes: CI of CCyR and MMR, and 5-year EFS. Of note, high risk stratified by EUTOS score demonstrated the least favorable outcomes with strongest p-values (Table 1). Conclusion By simply comparing the p-values, our data may implicate that high risk group discriminated by the EUTOS score is predicted with more unfavorable outcomes in achieving CCyR, MMR and survival after IM frontline therapy. Furthermore, the lack of statistically significant difference between outcomes of low and INT risk groups by conventional risk models may challenge the need for future classification of INT from low risk in this era of TKI. Disclosures: No relevant conflicts of interest to declare.

The main objective of this experimental study was to investigate the spray atomization process of a multi-hole gasoline direct injector by characterizing the basic process of single-jet atomization as well as complex phenomena such as air entrainment and jet interactions. We measured the droplet size and velocity using a phase Doppler particle analysis system at different measurement distances and different injection pressures in both the parallel direction and the orthogonal direction with respect to spray propagation. In addition, we calculated the Weber numbers to characterize further the spray atomization process. Our experimental results showed that the droplet velocities followed similar trends for different measurement distances but that the peak value decreased as the distance increased. Furthermore, a leading edge of the spray was observed at the initial stage of injection but disappeared as the measurement distance increased. Based on the droplet diameter distribution, we confirmed that increasing the distance and air entrainment had effects on the jet atomization process. Air entrainment was seen at the edges of both sides of the jet when the droplet diameter was less than 23 mm and the droplet was travelling at a low velocity, and the spray atomization process was more activated under air entrainment conditions. A comparison of different injection pressures confirmed that the injection pressure plays an important role in droplet break-up.

n-3 PUFA such as EPA and DHA as well as oestrogen have been reported to decrease blood levels of cholesterol, but their underlying mechanism is unclear. The purpose of this study was to determine the effects of the combination of n-3 PUFA supplementation and oestrogen injection on hepatic cholesterol metabolism. Rats were fed a modified AIN-93G diet with 0, 1 or 2 % n-3 PUFA (EPA + DHA) relative to the total energy intake for 12 weeks. Rats were surgically ovariectomised at week 8, and, after 1-week recovery, rats were injected with 17β-oestradiol-3-benzoate (E 2 ) or maize oil for the last 3 weeks. Supplementation with n-3 PUFA and E 2 injection significantly increased the ratio of the hepatic expression of phosphorylated AMP activated protein kinase (p-AMPK):AMP activated protein kinase (AMPK) and decreased sterol regulatory element-binding protein-2, 3-hydroxy-3-methylglutaryl coenzyme A reductase and proprotein convertase subtilisin/kexin type 9. Supplementation with n-3 PUFA increased hepatic expression of cholesterol 7α-hydroxylase (CYP7A1), sterol 12α-hydroxylase (CYP8B1) and sterol 27-hydroxylase (CYP27A1); however, E 2 injection decreased CYP7A1 and CYP8B1 but not CYP27A1. Additionally, E 2 injection increased hepatic expression of oestrogen receptor-α and β. In conclusion, n-3 PUFA supplementation and E 2 injection had synergic hypocholesterolaemic effects by down-regulating hepatic cholesterol synthesis (n-3 PUFA and oestrogen) and up-regulating bile acid synthesis (n-3 PUFA) in ovariectomised rats.