Nonlinear Quantum Behavior of Ultrashort-Pulse Optical Parametric Oscillators

The quantum features of ultrashort-pulse optical parametric oscillators (OPOs) are theoretically investigated in the nonlinear regime near and above threshold. Starting from basic premises of input-output theory, we derive a general quantum model for pulsed OPOs subject to χ(2) interactions between a multimode signal cavity and a non-resonant broadband pump field, elucidating time scale conditions required for such pulsed OPOs to admit an input-output description. By employing a supermode decomposition of the nonlinear Lindblad operators governing pump-signal interactions, we perform multimode quantum simulations in the regime of strong nonlinearity and study effects such as pump depletion and corrections to the squeezing spectrum of the linearized model. We observe non-Gaussian states with Wigner function negativity and show that multimode interactions with the pump can act as decoherence channels

Nonlinear Quantum Behavior of Ultrashort-Pulse Optical Parametric Oscillators

The quantum features of ultrashort-pulse optical parametric oscillators (OPOs) are theoretically investigated in the nonlinear regime near and above threshold. Starting from basic premises of input-output theory, we derive a general quantum model for pulsed OPOs subject to χ(2) interactions between a multimode signal cavity and a non-resonant broadband pump field, elucidating time scale conditions required for such pulsed OPOs to admit an input-output description. By employing a supermode decomposition of the nonlinear Lindblad operators governing pump-signal interactions, we perform multimode quantum simulations in the regime of strong nonlinearity and study effects such as pump depletion and corrections to the squeezing spectrum of the linearized model. We observe non-Gaussian states with Wigner function negativity and show that multimode interactions with the pump can act as decoherence channels

Novel method to rescue a lethal phenotype through integration of target gene onto the X-chromosome.

The loss-of-function mutations of serine protease inhibitor, Kazal type 1 (SPINK1) gene are associated with human chronic pancreatitis, but the underlying mechanisms remain unknown. We previously reported that mice lacking Spink3, the murine homologue of human SPINK1, die perinatally due to massive pancreatic acinar cell death, precluding investigation of the effects of SPINK1 deficiency. To circumvent perinatal lethality, we have developed a novel method to integrate human SPINK1 gene on the X chromosome using Cre-loxP technology and thus generated transgenic mice termed "X-SPINK1". Consistent with the fact that one of the two X chromosomes is randomly inactivated, X-SPINK1 mice exhibit mosaic pattern of SPINK1 expression. Crossing of X-SPINK1 mice with Spink3+/- mice rescued perinatal lethality, but the resulting Spink3-/-;XXSPINK1 mice developed spontaneous pancreatitis characterized by chronic inflammation and fibrosis. The results show that mice lacking a gene essential for cell survival can be rescued by expressing this gene on the X chromosome. The Spink3-/-;XXSPINK1 mice, in which this method has been applied to partially restore SPINK1 function, present a novel genetic model of chronic pancreatitis

Involvement of autophagy in trypsinogen activation within the pancreatic acinar cells

Autophagy is mostly a nonselective bulk degradation system within cells. Recent reports indicate that autophagy can act both as a protector and killer of the cell depending on the stage of the disease or the surrounding cellular environment (for review see Cuervo, A.M. 2004. Trends Cell Biol. 14:70–77). We found that cytoplasmic vacuoles induced in pancreatic acinar cells by experimental pancreatitis were autophagic in origin, as demonstrated by microtubule-associated protein 1 light chain 3 expression and electron microscopy experiments. To analyze the role of macroautophagy in acute pancreatitis, we produced conditional knockout mice lacking the autophagy-related 5 gene in acinar cells. Acute pancreatitis was not observed, except for very mild edema in a restricted area, in conditional knockout mice. Unexpectedly, trypsinogen activation was greatly reduced in the absence of autophagy. These results suggest that autophagy exerts devastating effects in pancreatic acinar cells by activation of trypsinogen to trypsin in the early stage of acute pancreatitis through delivering trypsinogen to the lysosome

A deep ATCA 20cm radio survey of the AKARI Deep Field South near the South Ecliptic Pole

The results of a deep 20 cm radio survey at 20 cm are reported of the AKARI Deep Field South (ADF-S) near the South Ecliptic Pole (SEP), using the Australia Telescope Compact Array telescope, ATCA. The survey has 1 sigma detection limits ranging from 18.7--50 microJy per beam over an area of ~1.1 sq degrees, and ~2.5 sq degrees to lower sensitivity. The observations, data reduction and source count analysis are presented, along with a description of the overall scientific objectives, and a catalogue containing 530 radio sources detected with a resolution of 6.2" x 4.9". The derived differential source counts show a pronounced excess of sources fainter than ~1 mJy, consistent with an emerging population of star forming galaxies. Cross-correlating the radio with AKARI sources and archival data we find 95 cross matches, with most galaxies having optical R-magnitudes in the range 18-24 mag, and 52 components lying within 1" of a radio position in at least one further catalogue (either IR or optical). We have reported redshifts for a sub-sample of our catalogue finding that they vary between galaxies in the local universe to those having redshifts of up to 0.825. Associating the radio sources with the Spitzer catalogue at 24 microns, we find 173 matches within one Spitzer pixel, of which a small sample of the identifications are clearly radio loud compared to the bulk of the galaxies. The radio luminosity plot and a colour-colour analysis suggest that the majority of the radio sources are in fact luminous star forming galaxies, rather than radio-loud AGN. There are additionally five cross matches between ASTE or BLAST submillimetre galaxies and radio sources from this survey, two of which are also detected at 90 microns, and 41 cross-matches with submillimetre sources detected in the Herschel HerMES survey Public Data release.Comment: MNRAS accepted and in press 9 July 2012: 28 pages, 15 Figures, 17 Table

Real-world effectiveness and safety analysis of carfilzomib-lenalidomide-dexamethasone and carfilzomib-dexamethasone in relapsed/refractory multiple myeloma: a multicenter retrospective analysis

Background: Little is known about the real-world survival benefits and safety profiles of carfilzomib-lenalidomide-dexamethasone (KRd) and carfilzomib-dexamethasone (Kd). Methods: We performed a retrospective analysis to evaluate their efficacy and safety in 157 patients registered in the Kansai Myeloma Forum database. Results: A total of 107 patients received KRd. Before KRd, 99% of patients had received bortezomib (54% were refractory disease), and 82% had received lenalidomide (57% were refractory disease). The overall response rate (ORR) was 68.2%. The median progression-free survival (PFS) and overall survival (OS) were 8.8 and 29.3 months, respectively. Multivariate analysis showed that reduction of the carfilzomib dose and non-IgG M protein were significantly associated with lower PFS and reduction of the carfilzomib dose and refractoriness to prior bortezomib-based regimens were significantly associated with lower OS. A total of 50 patients received Kd. Before Kd, 96% of patients had received bortezomib (54% were refractory disease). The ORR was 62.0%. The median PFS and OS were 7.1 and 20.9 months, respectively. Based on the multivariate analysis, reduction of the carfilzomib dose and International Staging System Stage III (ISS III) were significantly associated with lower PFS. Grade III or higher adverse events were observed in 48% of KRd cases and 54% of Kd cases. Cardiovascular events, cytopenia, and infections were frequent, and 4 KRd patients died due to heart failure, arrhythmia, cerebral hemorrhage, and pneumonia. Conclusion: Our analysis showed that an adequate dose of carfilzomib is important for achieving the best survival benefits in a real-world setting. Adverse effects after KRd and Kd therapy should also be considered