Point source detection in infrared astronomical surveys

Data processing techniques useful for infrared astronomy data analysis systems are reported. This investigation is restricted to consideration of data from space-based telescope systems operating as survey instruments. In this report the theoretical background for specific point-source detection schemes is completed, and the development of specific algorithms and software for the broad range of requirements is begun

Efficient computer algorithms for infrared astronomy data processing

Data processing techniques to be studied for use in infrared astronomy data analysis systems are outlined. Only data from space based telescope systems operating as survey instruments are considered. Resulting algorithms, and in some cases specific software, will be applicable for use with the infrared astronomy satellite (IRAS) and the shuttle infrared telescope facility (SIRTF). Operational tests made during the investigation use data from the celestial mapping program (CMP). The overall task differs from that involved in ground-based infrared telescope data reduction

A MASS PSYCHOLOGICAL PERSPECTIVE ON FINANCIAL MARKETS

Numerous research works indicate that the cycle of boom and crisis can be regarded as a natural element in financial market history. On the other hand, there is a rich discussion among practitioners and academics on the origins of the recent global economic and financial crisis, which led the world into the deepest and most severe downturn since the Great Depression in the 1930s. An explanation solely based on the collapse of the U.S. housing bubble and its effects seems far too short-sighted. In addition to economic elucidations and rationalizations, there are also behavioral and socio-economic explanations, which take into account the powerful social and psychological forces at work in financial markets. This article approaches the discussion from a mass psychological perspective. Starting from the shortcomings of mainstream economic approaches in predicting market trends and their underlying trading behavior realistically, the paper elucidates postulated mechanisms behind mass phenomena and provides a concise review of literature on collective dynamics in financial markets. We then delineate previous research on the distinction between mass phenomena and attempt to transfer this theoretical framework to financial markets. Consequently the final section discusses directions for future research to extend the foundations of the theoretical frame of reference

Improved optical activation of ion-implanted Zn acceptors in GaN by annealing under N2 overpressure

We investigated the properties of ion-implanted GaN:Zn annealed under various conditions using photoluminescence (PL) and high resolution x-ray diffraction (HRXRD). Epitaxial GaN/sapphire of high optical quality was ion-implanted with a 1013 cm−2 dose of Zn+ ions at 200 keV. The sample was capped with 200 Å of SiNx and then diced into numerous pieces which were annealed under varied conditions in an attempt to optically activate the Zn. Annealing was performed in a tube furnace under flowing N2, an atmospheric pressure MOCVD reactor under flowing NH3 or N2, and under an N2 overpressure of 190 atm. The observed improvement in the optical quality of GaN:Zn annealed under N2 overpressure yields further insights into the trade-off between defect annealing and N loss from the GaN crysta

Stability and Robustness of Distributed Suboptimal Model Predictive Control

In distributed model predictive control (MPC), the control input at each sampling time is computed by solving a large-scale optimal control problem (OCP) over a finite horizon using distributed algorithms. Typically, such algorithms require several (virtually, infinite) communication rounds between the subsystems to converge, which is a major drawback both computationally and from an energetic perspective (for wireless systems). Motivated by these challenges, we propose a suboptimal distributed MPC scheme in which the total communication burden is distributed also in time, by maintaining a running solution estimate for the large-scale OCP and updating it at each sampling time. We demonstrate that, under some regularity conditions, the resulting suboptimal MPC control law recovers the qualitative robust stability properties of optimal MPC, if the communication budget at each sampling time is large enough

Efficient optical activation of ion-implanted Zn acceptors in GaN by annealing under 10 kbar N2 overpressure

We continue our investigations into the optical activation of Zn-implanted GaN annealed under ever higher N2 overpressure. The samples studied were epitaxial GaN/sapphire layers of good optical quality which were implanted with a 1013 cm−2 dose of Zn+ ions at 200 keV, diced into equivalent pieces and annealed under 10 kbar of N2. The N2 overpressure permitted annealing at temperatures up to 1250°C for 1 hr without GaN decomposition. The blue Zn-related photoluminescence (PL) signal rises sharply with increasing anneal temperature. The Zn-related PL intensity in the implanted sample annealed at 1250°C exceeded that of the epitaxially doped GaN:Zn standard proving that high temperature annealing of GaN under kbar N2 overpressure can effectively remove implantation damage and efficiently activate implanted dopants in GaN. We propose a lateral LED device which could be fabricated using ion implanted dopants activated by high temperature annealing at high pressur

If blocking potency of ivabradine is preserved under elevated endotoxin levels in human atrial myocytes

AbstractLower heart rate is associated with better survival in patients with multiple organ dysfunction syndrome (MODS), a disease mostly caused by sepsis. The benefits of heart rate reduction by ivabradine during MODS are currently being investigated in the MODIfY clinical trial. Ivabradine is a selective inhibitor of the pacemaker current If and since If is impaired by lipopolysaccharide (LPS, endotoxin), a trigger of sepsis, we aimed to explore If blocking potency of ivabradine under elevated endotoxin levels in human atrial cardiomyocytes. Treatment of myocytes with S-LPS (containing the lipid A moiety, a core oligosaccharide and an O-polysaccharide chain) but not R595 (an O-chain lacking LPS-form) caused If inhibition under acute and chronic septic conditions. The specific interaction of S-LPS but not R595 to pacemaker channels HCN2 and HCN4 proves the necessity of O-chain for S-LPS–HCN interaction. The efficacy of ivabradine to block If was reduced under septic conditions, an observation that correlated with lower intracellular ivabradine concentrations in S-LPS- but not R595-treated cardiomyocytes. Computational analysis using a sinoatrial pacemaker cell model revealed that despite a reduction of If under septic conditions, ivabradine further decelerated pacemaking activity. This novel finding, i.e. If inhibition by ivabradine under elevated endotoxin levels in vitro, may provide a molecular understanding for the efficacy of this drug on heart rate reduction under septic conditions in vivo, e.g. the MODIfY clinical trial

Metabolite and transcriptome analysis during fasting suggest a role for the p53-Ddit4 axis in major metabolic tissues

BACKGROUND: Fasting induces specific molecular and metabolic adaptions in most organisms. In biomedical research fasting is used in metabolic studies to synchronize nutritional states of study subjects. Because there is a lack of standardization for this procedure, we need a deeper understanding of the dynamics and the molecular mechanisms in fasting. RESULTS: We investigated the dynamic changes of liver gene expression and serum parameters of mice at several time points during a 48 hour fasting experiment and then focused on the global gene expression changes in epididymal white adipose tissue (WAT) as well as on pathways common to WAT, liver, and skeletal muscle. This approach produced several intriguing insights: (i) rather than a sequential activation of biochemical pathways in fasted liver, as current knowledge dictates, our data indicates a concerted parallel response; (ii) this first characterization of the transcriptome signature of WAT of fasted mice reveals a remarkable activation of components of the transcription apparatus; (iii) most importantly, our bioinformatic analyses indicate p53 as central node in the regulation of fasting in major metabolic tissues; and (iv) forced expression of Ddit4, a fasting-regulated p53 target gene, is sufficient to augment lipolysis in cultured adipocytes. CONCLUSIONS: In summary, this combination of focused and global profiling approaches provides a comprehensive molecular characterization of the processes operating during fasting in mice and suggests a role for p53, and its downstream target Ddit4, as novel components in the transcriptional response to food deprivation

Denosumab treatment for fibrous dysplasia

Fibrous dysplasia (FD) is a skeletal disease caused by somatic activating mutations of the cyclic adenosine monophosphate (cAMP)‐regulating protein, α‐subunit of the Gs stimulatory protein (G s α). These mutations lead to replacement of normal bone by proliferative osteogenic precursors, resulting in deformity, fracture, and pain. Medical treatment has been ineffective in altering the disease course. Receptor activator of NF‐κB ligand (RANKL) is a cell‐surface protein involved in many cellular processes, including osteoclastogenesis, and is reported to be overexpressed in FD‐like bone cells. Denosumab is a humanized monoclonal antibody to RANKL approved for treatment of osteoporosis and prevention of skeletal‐related events from bone metastases. We present the case of a 9‐year‐old boy with severe FD who was treated with denosumab for a rapidly expanding femoral lesion. Immunohistochemical staining on a pretreatment bone biopsy specimen revealed marked RANKL expression. He was started on monthly denosumab, with an initial starting dose of 1 mg/kg and planned 0.25 mg/kg dose escalations every 3 months. Over 7 months of treatment he showed marked reduction in pain, bone turnover markers (BTMs), and tumor growth rate. Denosumab did not appear to impair healing of a femoral fracture that occurred while on treatment. With initiation of treatment he developed hypophosphatemia and secondary hyperparathyroidism, necessitating supplementation with phosphorus, calcium, and calcitriol. BTMs showed rapid and sustained suppression. With discontinuation there was rapid and dramatic rebound of BTMs with cross‐linked C‐telopeptide (reflecting osteoclast activity) exceeding pretreatment levels, accompanied by severe hypercalcemia. In this child, denosumab lead to dramatic reduction of FD expansion and FD‐related bone pain. Denosumab was associated with clinically significant disturbances of mineral metabolism both while on treatment and after discontinuation. Denosumab treatment of FD warrants further study to confirm efficacy and determine potential morbidity, as well as to determine the mechanism of RANKL in the pathogenesis of FD and related bone marrow stromal cell diseases. © 2012 American Society for Bone and Mineral Research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92121/1/1603_ftp.pd

Saxagliptin but Not Sitagliptin Inhibits CaMKII and PKC via DPP9 Inhibition in Cardiomyocytes

Some oral anti-hyperglycemic drugs, including gliptins that inhibit dipeptidyl peptidase 4 (DPP4), have been linked to the increased risk of heart failure (HF) in type-2 diabetic patients. While the cardiovascular safety trial, TECOS, revealed no link between sitagliptin and the risk of HF, a substantial 27% increase in the hospitalization for HF was observed in type-2 diabetic patients treated with saxagliptin within the SAVOR-TIMI 53 trial. A previous in vitro study revealed that saxagliptin impairs the Ca2+/calmodulin-dependent protein kinase II (CaMKII)-phospholamban (PLB)-sarcoplasmic reticulum Ca2+-ATPase 2a axis and protein kinase C (PKC) activity in cardiomyocytes leading to impaired cardiac contractility and electrophysiological function. However, the link between saxagliptin and its target proteins (CaMKII and PKC) remains to be explored. Since DPP8 and DPP9 (but not DPP4) are expressed by cardiomyocytes and saxagliptin is internalized by cardiomyocytes, we investigated whether DPP8/9 contribute to saxagliptin-mediated inhibition of CaMKII and PKC activity. Structural analysis revealed that the DPP4-saxagliptin interaction motif (S630, Y547) for the cyanopyrrolidine group is conserved in DPP8 (S755, Y669) and DPP9 (S730, Y644). Conversely, F357 that facilitates binding of the anchor lock domain of sitagliptin in the S2 extensive subsite of DPP4 is not conserved in DPP8/9. In parallel, unlike saxagliptin, sitagliptin did not affect phosphorylation of CaMKII/PLB or activity of PKC in HL-1 cardiomyocytes. These findings were recapitulated by pharmacological inhibition (TC-E-5007, a DPP8/9 antagonist) and knock-down of DPP9 (but not DPP8). In primary mouse ventricular cardiomyocytes, saxagliptin (but not sitagliptin) impaired Ca2+ transient relaxation and prolonged action potential duration (APD). These results suggest that saxagliptin-DPP9 interaction impairs the CaMKII-PLB and PKC signaling in cardiomyocytes. We reveal a novel and potential role of DPP9 in cardiac signaling. The interaction of saxagliptin with DPP9 may represent an underlying mechanism for the link between saxagliptin and HF. Elucidation of saxagliptin-DPP9 interaction and downstream events may foster a better understanding of the role of gliptins as modulators of cardiac signaling