Low-threshold vertical-cavity surface-emitting lasers based onoxide-confinement and high contrast distributed Bragg reflectors

The interest in low-threshold vertical-cavity surface-emitting lasers (VCSEL's) is increased by the demonstration of the small size, low loss optical mode due to oxide-confinement in the Fabry-Perot microcavity laser. Intense recent work in this area has resulted in numerous record breaking demonstrations of low-threshold current, high wall-plug efficiency, and high speed. In this paper, we discuss the impact of the dielectric cavity design to enhance control of the optical mode. We argue that high contrast dielectric mirrors can become an important design approach, especially for small apertures limited by diffraction loss. Experimental results are compared for different types of mirror and aperture designs     

Factors Affecting Flow-Mediated Vasodilatation in Hemodialysis Patients

Clinical manifestation of overt vascular disease may be preceded for years by endothelial dysfunction. Objective: This study was undertaken to evaluate endothelial function in ESRD patients and correlation between endothelial function and clinical and biochemical parameters. Methods: 32 stable ESRD patients (male : female = 16 : 16, average age: 55.2 ± 13.0) on hemodialysis were included. A 10‐MHz ultrasound transducer was used to image the brachial artery. Brachial artery diameter was measured, and reactive hyperemia was induced by inflation to 250 mmHg for 5 min and then deflation of a pneumatic cuff. After release of the cuff, brachial artery diameter was measured. Results: In the entire study population and non‐diabetic group, the %FMD (% flow‐mediated dilatation, % change of brachial artery diameter between before and after cuff inflation) did not show any significant correlation with duration of dialysis, age, hypertension, albumin, CRP, total cholesterol, LDL and HDL cholesterol, and triglyceride. However, the %FMD of diabetic patients was lower than that of non‐diabetics. Among the patients with diabetes, the group of patients with FMD of <5.2% showed significant lower serum albumin and significantly higher ln(CRP) levels compared to the group of patients with FMD ≥5.2%. The %FMD showed significant positive correlation with serum albumin level and significant negative correlation with ln(CRP) in diabetic patients. Conclusion: These findings suggest that endothelial dysfunction, estimated by FMD, was significantly more prominent in diabetic ESRD, especially with low serum albumin and high CRP levels.     

Design of a Drilling Torque Controller for a Machining Center

In the drilling process, cutting torque control through feedrate manipulation has significant benefits in prevention of tool breakage and reduction of machine tool vibration and tool wear. In this paper, a PID torque controller was designed for real time drilling torque control in a machining centre. The drilling torque was estimated from the spindle motor current and regulated by feedrate control. The plant including the feed drive system, cutting process, and spindle system was modelled for controller design. For a certain cutting condition, the Ziegler-Nichols method was used to determine the proportional gain and derivative and integral control action times of the controller. Also, the root locus plot was used to tune the proportional gain of the controller. A simple method was also suggested to obtain the tuned controller gain instead of the Ziegler-Nichols method and the root locus plot for an arbitrary cutting condition. Experimental works have been performed to verify the performance of the proposed controller. It is shown that the gain tuning is essential for enhancement of the controller performance and the designed controller can regulate the drilling torque well at a given reference level.Nomenclature G_fc(s) transfer function of combined system of feed drive and cutting process - G_s(s) transfer function of spindle system - G_p(s) transfer function of plant - G_CL(s) transfer function of closed loop system - G_con(s) transfer function of controller - _fc1, _fc2 time constants of combined system of feed drive and cutting process - _s time constant of spindle system - K controller gain - K_c cutting process gain - K_s spindle motor current gain - K_plant plant gain - K_cr critical gain - K_p proportional gain of controller - K_{p_tune} tuned proportional gain of controller - I_s spindle motor current - I_u,v,w u, v, and w phase current of spindle motor - I_idle idling current of spindle motor - damping ratio - T oscillation period of system response - T_c cutting torque - T_m motor torque - T_idle idling torque of spindle motor - T_i integral control action time - T_d derivative control action time     

Behavior of unirradiated Zr based uranium metal fuel under reactivity initiated accident conditions

Reactivity initiated accident (RIA) tests with 4 unirradiated Zr based uranium metal fuel rods were performed to establish a criterion which should be observed under RIA conditions. Of the four tests, fuel failures were observed in the two tests that experienced the maximum energy depositions of 188 and 212 cal/g, respectively. However, the fuel failures were not observed at the place of a maximum energy deposition but at the position where the thermocouples were installed; one failed at the position whose local energy deposition was 150 cal/g, and the other one at the place with energy deposition of 170 cal/g. The fuel failures seem to have occurred because excessive pressure, which was caused by the partial melting of the fuel meat, was applied to the cladding with a reduced thickness. However, other parts of the fuel rods including the place of a maximum energy deposition maintained their integrity and a big change in the temperature and pressure in the internal capsule, which would be an indication of the fragmentation and dispersion of the fuel meat into the internal capsule, was not observed. Visual inspection also showed that, except for the thermocouple positions, there was no trace of clad failure such as the formation of brittle cracks in the cladding or melting of the cladding. Therefore, for the Zr based uranium metal fuel rods, it can be concluded that the threshold energy deposition above which fragmentation and dispersion of fuel meat into the primary coolant system is expected to occur could be higher than 212 cal/g.     

Tiron Has Negative Effects on Osteogenic Differentiation via Mitochondrial Dysfunction in Human Periosteum-Derived Cells

Tiron is a potent antioxidant that counters the pathological effects of reactive oxygen species (ROS) production due to oxidative stress in various cell types. We examined the effects of tiron on mitochondrial function and osteoblastic differentiation in human periosteum-derived cells (hPDCs). Tiron increased mitochondrial activity and decreased senescence-associated β-galactosidase activity in hPDCs; however, it had a detrimental effect on osteoblastic differentiation by reducing alkaline phosphatase (ALP) activity and alizarin red-positive mineralization, regardless of H₂O₂ treatment. Osteoblast-differentiating hPDCs displayed increased ROS production compared with non-differentiating hPDCs, and treatment with tiron reduced ROS production in the differentiating cells. Antioxidants decreased the rates of oxygen consumption and ATP production, which are increased in hPDCs during osteoblastic differentiation. In addition, treatment with tiron reduced the levels of most mitochondrial proteins, which are increased in hPDCs during culture in osteogenic induction medium. These results suggest that tiron exerts negative effects on the osteoblastic differentiation of hPDCs by causing mitochondrial dysfunction.     

Crystal Structure and Biochemical Analysis of a Cytochrome P450 CYP101D5 from Sphingomonas echinoides

Cytochrome P450 enzymes (CYPs) are heme-containing enzymes that catalyze hydroxylation with a variety of biological molecules. Despite their diverse activity and substrates, the structures of CYPs are limited to a tertiary structure that is similar across all the enzymes. It has been presumed that CYPs overcome substrate selectivity with highly flexible loops and divergent sequences around the substrate entrance region. Here, we report the newly identified CYP101D5 from Sphingomonas echinoides. CYP101D5 catalyzes the hydroxylation of β-ionone and flavonoids, including naringenin and apigenin, and causes the dehydrogenation of α-ionone. A structural investigation and comparison with other CYP101 families indicated that spatial constraints at the substrate-recognition site originate from the B/C loop. Furthermore, charge distribution at the substrate binding site may be important for substrate selectivity and the preference for CYP101D5.     

Effects of Loganin on Bone Formation and Resorption In Vitro and In Vivo

Osteoporosis is a disease caused by impaired bone remodeling that is especially prevalent in elderly and postmenopausal women. Although numerous chemical agents have been developed to prevent osteoporosis, arguments remain regarding their side effects. Here, we demonstrated the effects of loganin, a single bioactive compound isolated from Cornus officinalis, on osteoblast and osteoclast differentiation in vitro and on ovariectomy (OVX)-induced osteoporosis in mice in vivo. Loganin treatment increased the differentiation of mouse preosteoblast cells into osteoblasts and suppressed osteoclast differentiation in primary monocytes by regulating the mRNA expression levels of differentiation markers. Similar results were obtained in an osteoblast–osteoclast co-culture system, which showed that loganin enhanced alkaline phosphatase (ALP) activity and reduced TRAP activity. In in vivo experiments, the oral administration of loganin prevented the OVX-induced loss of bone mineral density (BMD) and microstructure in mice and improved bone parameters. In addition, loganin significantly increased the serum OPG/RANKL ratio and promoted osteogenic activity during bone remodeling. Our findings suggest that loganin could be used as an alternative treatment to protect against osteoporosis.     

Monitoring Circulating Tumor DNA in Untreated Non-Small-Cell Lung Cancer Patients

Circulating tumor DNA (ctDNA) has been utilized to monitor the clinical course of patients of non-small-cell lung cancer (NSCLC) who receive therapies targeting druggable mutations. However, despite providing valuable information on how NSCLC would naturally progress, the clinical utility of ctDNA for clinical-course monitoring and prediction of treatment-naïve NSCLC patients without druggable mutations remain unknown. We longitudinally followed a total of 12 treatment-naïve NSCLC patients, who did not harbor EGFR and ALK mutations, by collecting clinical information, radiological data, and plasma samples. Changes in ctDNA levels and tumor burden (TB) were compared with each other. New metastasis development, volume doubling time (VDT), and overall survival (OS) were analyzed regarding ctDNA detection at diagnosis. ctDNA was detected in the plasma of seven (58.3%) patients. Changes in ctDNA levels correlated with those in TB in a substantial fraction (57.1%) of patients and was also associated with brain metastasis, tumor necrosis, or pneumonia in other patients. All patients with ctDNA detection developed new metastasis during follow-ups in the organs that had been devoid of metastasis at diagnosis. The patients without ctDNA detection did not develop new metastasis (median duration of follow-ups: 9.8 months). In addition, patients with ctDNA detection had shorter VDT (p = 0.039) and worse OS (p = 0.019) than those without ctDNA detection. The natural course of NSCLC progression can be monitored by measuring ctDNA levels. Detection of ctDNA at diagnosis can predict development of new metastasis, rapid tumor growth and poor survival of NSCLC patients.     

SHMT2 Induces Stemness and Progression of Head and Neck Cancer

Various enzymes in the one-carbon metabolic pathway are closely related to the development of tumors, and they can all be potential targets for cancer therapy. Serine hydroxymethyltransferase2 (SHMT2), a key metabolic enzyme, is very important for the proliferation and growth of cancer cells. However, the function and mechanism of SHMT2 in head and neck cancer (HNC) are not clear. An analysis of The Cancer Genome Atlas (TCGA) data showed that the expression of SHMT2 was higher in tumor tissue than in normal tissue, and its expression was significantly associated with male sex, aggressive histological grade, lymph node metastasis, distant metastasis, advanced TNM stage, and lymphovascular invasion in HNC. SHMT2 knockdown in FADU and SNU1041 cell lines significantly inhibited cell proliferation, colony formation, migration, and invasion. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses using TCGA data revealed that SHMT2 was closely related to cancer stem cell regulation and maintenance. Furthermore, we found that silencing SHMT2 inhibited the expression of stemness markers and tumor spheroid formation compared with a control group. On the contrary, stemness markers were significantly increased after SHMT2 overexpression in HEP-2 cells. Interestingly, we found that knocking down SHMT2 reduced the expression of genes related to the Notch and Wnt pathways. Finally, silencing SHMT2 significantly reduced tumor growth and decreased stemness markers in a xenograft model. Taken together, our study suggests that targeting SHMT2 may play an important role in inhibiting HNC progression.     

The Role of IL-7 and IL-7R in Cancer Pathophysiology and Immunotherapy

Interleukin-7 (IL-7) is a multipotent cytokine that maintains the homeostasis of the immune system. IL-7 plays a vital role in T-cell development, proliferation, and differentiation, as well as in B cell maturation through the activation of the IL-7 receptor (IL-7R). IL-7 is closely associated with tumor development and has been used in cancer clinical research and therapy. In this review, we first summarize the roles of IL-7 and IL-7Rα and their downstream signaling pathways in immunity and cancer. Furthermore, we summarize and discuss the recent advances in the use of IL-7 and IL-7Rα as cancer immunotherapy tools and highlight their potential for therapeutic applications. This review will help in the development of cancer immunotherapy regimens based on IL-7 and IL-7Rα, and will also advance their exploitation as more effective and safe immunotherapy tools.