Instantaneous frequency and amplitude of complex signals based on quaternion Fourier transform

The ideas of instantaneous amplitude and phase are well understood for signals with real-valued samples, based on the analytic signal which is a complex signal with one-sided Fourier transform. We extend these ideas to signals with complex-valued samples, using a quaternion-valued equivalent of the analytic signal obtained from a one-sided quaternion Fourier transform which we refer to as the hypercomplex representation of the complex signal. We present the necessary properties of the quaternion Fourier transform, particularly its symmetries in the frequency domain and formulae for convolution and the quaternion Fourier transform of the Hilbert transform. The hypercomplex representation may be interpreted as an ordered pair of complex signals or as a quaternion signal. We discuss its derivation and properties and show that its quaternion Fourier transform is one-sided. It is shown how to derive from the hypercomplex representation a complex envelope and a phase. A classical result in the case of real signals is that an amplitude modulated signal may be analysed into its envelope and carrier using the analytic signal provided that the modulating signal has frequency content not overlapping with that of the carrier. We show that this idea extends to the complex case, provided that the complex signal modulates an orthonormal complex exponential. Orthonormal complex modulation can be represented mathematically by a polar representation of quaternions previously derived by the authors. As in the classical case, there is a restriction of non-overlapping frequency content between the modulating complex signal and the orthonormal complex exponential. We show that, under these conditions, modulation in the time domain is equivalent to a frequency shift in the quaternion Fourier domain. Examples are presented to demonstrate these concepts

Segmentation of plate coupling, fate of subduction fluids, and modes of arc magmatism in Cascadia, inferred from magnetotelluric resistivity

Author Posting. © American Geophysical Union, 2014. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry, Geophysics, Geosystems 15 (2014): 4230–4253, doi:10.1002/2014GC005509.Five magnetotelluric (MT) profiles have been acquired across the Cascadia subduction system and transformed using 2-D and 3-D nonlinear inversion to yield electrical resistivity cross sections to depths of ∼200 km. Distinct changes in plate coupling, subduction fluid evolution, and modes of arc magmatism along the length of Cascadia are clearly expressed in the resistivity structure. Relatively high resistivities under the coasts of northern and southern Cascadia correlate with elevated degrees of inferred plate locking, and suggest fluid- and sediment-deficient conditions. In contrast, the north-central Oregon coastal structure is quite conductive from the plate interface to shallow depths offshore, correlating with poor plate locking and the possible presence of subducted sediments. Low-resistivity fluidized zones develop at slab depths of 35–40 km starting ∼100 km west of the arc on all profiles, and are interpreted to represent prograde metamorphic fluid release from the subducting slab. The fluids rise to forearc Moho levels, and sometimes shallower, as the arc is approached. The zones begin close to clusters of low-frequency earthquakes, suggesting fluid controls on the transition to steady sliding. Under the northern and southern Cascadia arc segments, low upper mantle resistivities are consistent with flux melting above the slab plus possible deep convective backarc upwelling toward the arc. In central Cascadia, extensional deformation is interpreted to segregate upper mantle melts leading to underplating and low resistivities at Moho to lower crustal levels below the arc and nearby backarc. The low- to high-temperature mantle wedge transition lies slightly trenchward of the arc.Phil Wannamaker and Virginie Maris gratefully acknowledge funding by the U.S. National Science Foundation under grants EAR08–43725 and EAR08–38043 through the Earthscope and Geophysics programs. The 2D inversion capability received development support under U.S. Department of Energy contract DE-PS36-04GO94001. Rob Evans was supported through Earthscope grant EAR08–44041 and Shane McGary through a National Defense Science and Engineering Graduate (NDSEG) fellowship. Fieldwork in Canada was made possible by an NSERC Discovery Grant and a Canadian Foundation for Innovation award to Martyn Unsworth.2015-05-1

Eculizumab in paraxysmal nocturnal haemogloburinia and atypical haemolytic syndrome 10-year pharmacovigilance analysis

Eculizumab is the first and only medication approved for paroxysmal nocturnal haemoglobinuria (PNH) and atypical haemolytic uraemic syndrome (aHUS) treatment. However, eculizumab safety based on long‐term pharmacovigilance is unknown. This analysis summarises safety data collected from spontaneous and solicited sources from 16 March 2007 through 1 October 2016. Cumulative exposure to eculizumab was 28 518 patient‐years (PY) (PNH, 21 016 PY; aHUS, 7502 PY). Seventy‐six cases of meningococcal infection were reported (0·25/100 PY), including eight fatal PNH cases (0·03/100 PY). Susceptibility to meningococcal infections remained the key risk in patients receiving eculizumab. The meningococcal infection rate decreased over time; related mortality remained steady. The most commonly reported serious nonmeningococcal infections were pneumonia (11·8%); bacteraemia, sepsis and septic shock (11·1%); urinary tract infection (4·1%); staphylococcal infection (2·6%); and viral infection (2·5%). There were 434 reported cases of eculizumab exposure in pregnant women; of 260 cases with known outcomes, 70% resulted in live births. Reporting rates for solid tumours (≈0·6/100 PY) and haematological malignancies (≈0·74/100 PY) remained stable over time. No new safety signals affecting the eculizumab benefit‐risk profile were identified. Continued awareness and implementation of risk mitigation protocols are essential to minimise risk of meningococcal and other Neisseria infections in patients receiving eculizumab

Transient anhedonia phenotype and altered circadian timing of behaviour during night-time dim light exposure in Per3(-/-) mice, but not wildtype mice.

Industrialisation greatly increased human night-time exposure to artificial light, which in animal models is a known cause of depressive phenotypes. Whilst many of these phenotypes are 'direct' effects of light on affect, an 'indirect' pathway via altered sleep-wake timing has been suggested. We have previously shown that the Period3 gene, which forms part of the biological clock, is associated with altered sleep-wake patterns in response to light. Here, we show that both wild-type and Per3(-/-) mice showed elevated levels of circulating corticosterone and increased hippocampal Bdnf expression after 3 weeks of exposure to dim light at night, but only mice deficient for the PERIOD3 protein (Per3(-/-)) exhibited a transient anhedonia-like phenotype, observed as reduced sucrose preference, in weeks 2-3 of dim light at night, whereas WT mice did not. Per3(-/-) mice also exhibited a significantly smaller delay in behavioural timing than WT mice during weeks 1, 2 and 4 of dim light at night exposure. When treated with imipramine, neither Per3(-/-) nor WT mice exhibited an anhedonia-like phenotype, and neither genotypes exhibited a delay in behavioural timing in responses to dLAN. While the association between both Per3(-/-) phenotypes remains unclear, both are alleviated by imipramine treatment during dim night-time light

Strengthening the reporting of genetic risk prediction studies (GRIPS): explanation and elaboration

The rapid and continuing progress in gene discovery for complex diseases is fuelling interest in the potential application of genetic risk models for clinical and public health practice. The number of studies assessing the predictive ability is steadily increasing, but they vary widely in completeness of reporting and apparent quality. Transparent reporting of the strengths and weaknesses of these studies is important to facilitate the accumulation of evidence on genetic risk prediction. A multidisciplinary workshop sponsored by the Human Genome Epidemiology Network developed a checklist of 25 items recommended for strengthening the reporting of Genetic RIsk Prediction Studies (GRIPS), building on the principles established by prior reporting guidelines. These recommendations aim to enhance the transparency, quality and completeness of study reporting, and thereby to improve the synthesis and application of information from multiple studies that might differ in design, conduct or analysis

Voluntary exercise can strengthen the circadian system in aged mice

Consistent daily rhythms are important to healthy aging according to studies linking disrupted circadian rhythms with negative health impacts. We studied the effects of age and exercise on baseline circadian rhythms and on the circadian system's ability to respond to the perturbation induced by an 8 h advance of the light:dark (LD) cycle as a test of the system's robustness. Mice (male, mPer2luc/C57BL/6) were studied at one of two ages: 3.5 months (n = 39) and >18 months (n = 72). We examined activity records of these mice under entrained and shifted conditions as well as mPER2::LUC measures ex vivo to assess circadian function in the suprachiasmatic nuclei (SCN) and important target organs. Age was associated with reduced running wheel use, fragmentation of activity, and slowed resetting in both behavioral and molecular measures. Furthermore, we observed that for aged mice, the presence of a running wheel altered the amplitude of the spontaneous firing rate rhythm in the SCN in vitro. Following a shift of the LD cycle, both young and aged mice showed a change in rhythmicity properties of the mPER2::LUC oscillation of the SCN in vitro, and aged mice exhibited longer lasting internal desynchrony. Access to a running wheel alleviated some age-related changes in the circadian system. In an additional experiment, we replicated the effect of the running wheel, comparing behavioral and in vitro results from aged mice housed with or without a running wheel (>21 months, n = 8 per group, all examined 4 days after the shift). The impact of voluntary exercise on circadian rhythm properties in an aged animal is a novel finding and has implications for the health of older people living with environmentally induced circadian disruption

Planar Tc99m – sestamibi scintimammography should be considered cautiously in the axillary evaluation of breast cancer protocols: Results of an international multicenter trial

BACKGROUND: Lymph node status is the most important prognostic indicator in breast cancer in recently diagnosed primary lesion. As a part of an interregional protocol using scintimammography with Tc99m compounds, the value of planar Tc99m sestamibi scanning for axillary lymph node evaluation is presented. Since there is a wide range of reported values, a standardized protocol of planar imaging was performed. METHODS: One hundred and forty-nine female patients were included prospectively from different regions. Their mean age was 55.1 ± 11.9 years. Histological report was obtained from 2.987 excised lymph nodes from 150 axillas. An early planar chest image was obtained at 10 min in all patients and a delayed one in 95 patients, all images performed with 740–925 MBq dose of Tc99m sestamibi. Blind lecture of all axillary regions was interpreted by 2 independent observers considering any well defined focal area of increased uptake as an involved axilla. Diagnostic values, 95% confidence intervals [CI] and also likelihood ratios (LR) were calculated. RESULTS: Node histology demonstrated tumor involvement in 546 out of 2987 lymph nodes. Sestamibi was positive in 30 axillas (25 true-positive) and negative in 120 (only 55 true-negative). The sensitivity corresponded to 27.8% [CI = 18.9–38.2] and specificity to 91.7% [81.6–97.2]. The positive and negative LR were 3.33 and 0.79, respectively. There was no difference between early and delayed images. Sensitivity was higher in patients with palpable lesions. CONCLUSION: This work confirmed that non tomographic Tc99m sestamibi scintimammography had a very low detection rate for axillary lymph node involvement and it should not be applied for clinical assessment of breast cancer

Endocrine Therapy Synergizes with SMAC Mimetics to Potentiate Antigen Presentation and Tumor Regression in Hormone Receptor-Positive Breast Cancer.

UNLABELLED: Immunotherapies have yet to demonstrate significant efficacy in the treatment of hormone receptor-positive (HR+) breast cancer. Given that endocrine therapy (ET) is the primary approach for treating HR+ breast cancer, we investigated the effects of ET on the tumor immune microenvironment (TME) in HR+ breast cancer. Spatial proteomics of primary HR+ breast cancer samples obtained at baseline and after ET from patients enrolled in a neoadjuvant clinical trial (NCT02764541) indicated that ET upregulated β2-microglobulin and influenced the TME in a manner that promotes enhanced immunogenicity. To gain a deeper understanding of the underlying mechanisms, the intrinsic effects of ET on cancer cells were explored, which revealed that ET plays a crucial role in facilitating the chromatin binding of RelA, a key component of the NF-κB complex. Consequently, heightened NF-κB signaling enhanced the response to interferon-gamma, leading to the upregulation of β2-microglobulin and other antigen presentation-related genes. Further, modulation of NF-κB signaling using a SMAC mimetic in conjunction with ET augmented T-cell migration and enhanced MHC-I-specific T-cell-mediated cytotoxicity. Remarkably, the combination of ET and SMAC mimetics, which also blocks prosurvival effects of NF-κB signaling through the degradation of inhibitors of apoptosis proteins, elicited tumor regression through cell autonomous mechanisms, providing additional support for their combined use in HR+ breast cancer. SIGNIFICANCE: Adding SMAC mimetics to endocrine therapy enhances tumor regression in a cell autonomous manner while increasing tumor immunogenicity, indicating that this combination could be an effective treatment for HR+ patients with breast cancer

Low-molecular-weight cyclin E: the missing link between biology and clinical outcome

Cyclin E, a key mediator of transition during the G(1)/S cellular division phase, is deregulated in a wide variety of human cancers. Our group recently reported that overexpression and generation of low-molecular-weight (LMW) isoforms of cyclin E were associated with poor clinical outcome among breast cancer patients. However, the link between LMW cyclin E biology in mediating a tumorigenic phenotype and clinical outcome is unknown. To address this gap in knowledge, we assessed the role of LMW isoforms in breast cancer cells; we found that these forms of cyclin E induced genomic instability and resistance to p21, p27, and antiestrogens in breast cancer. These findings suggest that high levels of LMW isoforms of cyclin E not only can predict failure to endocrine therapy but also are true prognostic indicators because of their influence on cell proliferation and genetic instability