Single-Photon Counting Detector Scalability for High Photon Efficiency Optical Communications Links

For high photon-efficiency deep space or low power optical communications links, such as the Orion Artemis-2 Optical Communications System (O2O) project, the received optical signal is attenuated to the extent that single- photon detectors are required. For direct-detection receivers operating at 1.55 m wavelength, single-photon detectors including Geiger-mode InGaAs avalanche photon diodes (APDs), and in particular superconducting nanowire single-photon detectors (SNSPDs) offer the highest sensitivity and fastest detection speeds. However, these photon detectors exhibit a recovery time between registered input pulses, effectively reducing the detection efficiency over the recovery interval, resulting in missed photon detections, reduced count rate, and ultimately limiting the achievable data rate. A method to overcome this limitation is to divide the received optical signal into multiple detectors in parallel. Here we analyze this approach for a receiver designed to receive a high photon efficiency serially concatenated pulse position modulation (SCPPM) input waveform. From measured count rate and efficiency data using commercial SNSPDs, we apply a model from which we determine the effective detection efficiency, or blocking loss, for different input signal rates. We analyze the scalability of adding detectors in parallel for different modulation orders and background levels to achieve desired data rates. Finally we show tradeoffs between the number of detectors and the required received optical power, useful for real link design considerations

Detector Channel Combining Results from a High Photon Efficiency Optical Communications Link Test Bed

The National Aeronautics and Space Administration (NASA) Glenn Research Center (GRC) is developing a low cost, scalable, photon-counting receiver prototype for space-to-ground optical communications links. The receiver is being tested in a test bed that emulates photon-starved space-to-ground optical communication links. The receiver uses an array of single-pixel fiber-coupled superconducting nanowire single-photon detectors. The receiver is designed to receive the high photon efficiency serially concatenated pulse position modulation (SCPPM) waveform specified in the Consultative Committee for Space Data Systems (CCSDS) Optical Communications Coding and Synchronization Blue Book Standard. The optical receiver consists of an array of single-pixel superconducting nanowire detectors, analog phase shifters for channel alignment, digitizers for each detector channel, and digital processing of the received signal. An overview of the test bed and arrayed receiver system is given. Simulation and system characterization results are presented. The data rate increase of using a four-channel arrayed detector system over using one single pixel nanowire detector is characterized. Results indicate that a single-pixel detector is capable of receiving data at a rate of 40 Mbps and a four-channel arrayed detector system is capable of receiving data at a rate of 130 Mbps

Real Time Optical Receiver Project

The goals for the Real Time Optical Receiver project are to Infuse Consultative Committee for Space Data Systems High Photon Efficiency standard into missions, such as Artemis and to provide a real time ground receiver solution (fiber device, detector, real time FPGA-based receiver) that is: (1) Scalable: data rate, atmosphere conditions, telescope aperture, etc., and (2) Uses COTS components when available and work with companies to move custom parts to COTS

Activity of immunoproteasome inhibitor ONX-0914 in acute lymphoblastic leukemia expressing MLL–AF4 fusion protein

Proteasome inhibitors bortezomib and carfilzomib are approved for the treatment of multiple myeloma and mantle cell lymphoma and have demonstrated clinical efficacy for the treatment of acute lymphoblastic leukemia (ALL). The t(4;11)(q21;q23) chromosomal translocation that leads to the expression of MLL–AF4 fusion protein and confers a poor prognosis, is the major cause of infant ALL. This translocation sensitizes tumor cells to proteasome inhibitors, but toxicities of bortezomib and carfilzomib may limit their use in pediatric patients. Many of these toxicities are caused by on-target inhibition of proteasomes in non-lymphoid tissues (e.g., heart muscle, gut, testicles). We found that MLL–AF4 cells express high levels of lymphoid tissue-specific immunoproteasomes and are sensitive to pharmacologically relevant concentrations of specific immunoproteasome inhibitor ONX-0914, even in the presence of stromal cells. Inhibition of multiple active sites of the immunoproteasomes was required to achieve cytotoxicity against ALL. ONX-0914, an inhibitor of LMP7 (ß5i) and LMP2 (ß1i) sites of the immunoproteasome, and LU-102, inhibitor of proteasome ß2 sites, exhibited synergistic cytotoxicity. Treatment with ONX-0914 significantly delayed the growth of orthotopic ALL xenograft tumors in mice. T-cell ALL lines were also sensitive to pharmacologically relevant concentrations of ONX-0914. This study provides a strong rationale for testing clinical stage immunoproteasome inhibitors KZ-616 and M3258 in ALL

Insights into the complex regulation of rpoS in Borrelia burgdorferi

Co-ordinated regulation of gene expression is required for the transmission and survival of Borrelia burgdorferi in different hosts. The sigma factor RpoS (σS), as regulated by RpoN (σ54), has been shown to regulate key virulence factors (e.g. OspC) required for these processes. As important, multiple signals (e.g. temperature, pH, cell density, oxygen) have been shown to increase the expression of σS-dependent genes; however, little is known about the signal transduction mechanisms that modulate the expression of rpoS. In this report we show that: (i) rpoS has a σ54-dependent promoter that requires Rrp2 to activate transcription; (ii) Rrp2Δ123, a constitutively active form of Rrp2, activated σ54-dependent transcription of rpoS/P-lacZ reporter constructs in Escherichia coli; (iii) quantitative reverse transcription polymerase chain reaction (QRT-PCR) experiments with reporter cat constructs in B. burgdorferi indicated that Rrp2 activated transcription of rpoS in an enhancer-independent fashion; and finally, (iv) rpoN is required for cell density- and temperature-dependent expression of rpoS in B. burgdorferi, but histidine kinase Hk2, encoded by the gene immediately upstream of rrp2, is not essential. Based on these findings, a model for regulation of rpoS has been proposed which provides mechanisms for multiple signalling pathways to modulate the expression of the σS regulon in B. burgdorferi

Dementias show differential physiological responses to salient sounds.

Abnormal responsiveness to salient sensory signals is often a prominent feature of dementia diseases, particularly the frontotemporal lobar degenerations, but has been little studied. Here we assessed processing of one important class of salient signals, looming sounds, in canonical dementia syndromes. We manipulated tones using intensity cues to create percepts of salient approaching ("looming") or less salient withdrawing sounds. Pupil dilatation responses and behavioral rating responses to these stimuli were compared in patients fulfilling consensus criteria for dementia syndromes (semantic dementia, n = 10; behavioral variant frontotemporal dementia, n = 16, progressive nonfluent aphasia, n = 12; amnestic Alzheimer's disease, n = 10) and a cohort of 26 healthy age-matched individuals. Approaching sounds were rated as more salient than withdrawing sounds by healthy older individuals but this behavioral response to salience did not differentiate healthy individuals from patients with dementia syndromes. Pupil responses to approaching sounds were greater than responses to withdrawing sounds in healthy older individuals and in patients with semantic dementia: this differential pupil response was reduced in patients with progressive nonfluent aphasia and Alzheimer's disease relative both to the healthy control and semantic dementia groups, and did not correlate with nonverbal auditory semantic function. Autonomic responses to auditory salience are differentially affected by dementias and may constitute a novel biomarker of these diseases

Humour processing in frontotemporal lobar degeneration: A behavioural and neuroanatomical analysis.

Humour is a complex cognitive and emotional construct that is vulnerable in neurodegenerative diseases, notably the frontotemporal lobar degenerations. However, humour processing in these diseases has been little studied. Here we assessed humour processing in patients with behavioural variant frontotemporal dementia (n = 22, mean age 67 years, four female) and semantic dementia (n = 11, mean age 67 years, five female) relative to healthy individuals (n = 21, mean age 66 years, 11 female), using a joint cognitive and neuroanatomical approach. We created a novel neuropsychological test requiring a decision about the humorous intent of nonverbal cartoons, in which we manipulated orthogonally humour content and familiarity of depicted scenarios. Structural neuroanatomical correlates of humour detection were assessed using voxel-based morphometry. Assessing performance in a signal detection framework and after adjusting for standard measures of cognitive function, both patient groups showed impaired accuracy of humour detection in familiar and novel scenarios relative to healthy older controls (p < .001). Patient groups showed similar overall performance profiles; however the behavioural variant frontotemporal dementia group alone showed a significant advantage for detection of humour in familiar relative to novel scenarios (p = .045), suggesting that the behavioural variant syndrome may lead to particular difficulty decoding novel situations for humour, while semantic dementia produces a more general deficit of humour detection that extends to stock comedic situations. Humour detection accuracy was associated with grey matter volume in a distributed network including temporo-parietal junctional and anterior superior temporal cortices, with predominantly left-sided correlates of processing humour in familiar scenarios and right-sided correlates of processing novel humour. The findings quantify deficits of core cognitive operations underpinning humour processing in frontotemporal lobar degenerations and suggest a candidate brain substrate in cortical hub regions processing incongruity and semantic associations. Humour is a promising candidate tool with which to assess complex social signal processing in neurodegenerative disease

Cultural value orientations, internalized homophobia, and accommodation in romantic relationships

In the present study, we examined the impact of cultural value orientations (i.e., the personally oriented value of individualism, and the socially oriented values of collectivism, familism, romanticism, and spiritualism) on accommodation (i.e., voice and loyalty, rather than exit and neglect, responses to partners' anger or criticism) in heterosexual and gay relationships; and we examined the impact of internalized homophobia (i.e., attitudes toward self, other, and disclosure) on accommodation specifically in gay relationships. A total of 262 heterosexuals (102 men and 162 women) and 857 gays (474 men and 383 women) participated in the present study. Consistent with hypotheses, among heterosexuals and gays, socially oriented values were significantly and positively related to accommodation (whereas the personally oriented value of individualism was unrelated to accommodation); and among gays in particular, internalized homophobia was significantly and negatively related to accommodation. Implications for the study of heterosexual and gay relationships are discussed. © 2005 by The Haworth Press, Inc. All rights reserved

Auditory conflict and congruence in frontotemporal dementia.

Impaired analysis of signal conflict and congruence may contribute to diverse socio-emotional symptoms in frontotemporal dementias, however the underlying mechanisms have not been defined. Here we addressed this issue in patients with behavioural variant frontotemporal dementia (bvFTD; n = 19) and semantic dementia (SD; n = 10) relative to healthy older individuals (n = 20). We created auditory scenes in which semantic and emotional congruity of constituent sounds were independently probed; associated tasks controlled for auditory perceptual similarity, scene parsing and semantic competence. Neuroanatomical correlates of auditory congruity processing were assessed using voxel-based morphometry. Relative to healthy controls, both the bvFTD and SD groups had impaired semantic and emotional congruity processing (after taking auditory control task performance into account) and reduced affective integration of sounds into scenes. Grey matter correlates of auditory semantic congruity processing were identified in distributed regions encompassing prefrontal, parieto-temporal and insular areas and correlates of auditory emotional congruity in partly overlapping temporal, insular and striatal regions. Our findings suggest that decoding of auditory signal relatedness may probe a generic cognitive mechanism and neural architecture underpinning frontotemporal dementia syndromes

Music models aberrant rule decoding and reward valuation in dementia.

Aberrant rule- and reward-based processes underpin abnormalities of socio-emotional behaviour in major dementias. However, these processes remain poorly characterized. Here we used music to probe rule decoding and reward valuation in patients with frontotemporal dementia (FTD) syndromes and Alzheimer's disease (AD) relative to healthy age-matched individuals. We created short melodies that were either harmonically resolved ('finished') or unresolved ('unfinished'); the task was to classify each melody as finished or unfinished (rule processing) and rate its subjective pleasantness (reward valuation). Results were adjusted for elementary pitch and executive processing; neuroanatomical correlates were assessed using voxel-based morphometry. Relative to healthy older controls, patients with behavioural variant FTD showed impairments of both musical rule decoding and reward valuation, while patients with semantic dementia showed impaired reward valuation but intact rule decoding, patients with AD showed impaired rule decoding but intact reward valuation and patients with progressive non-fluent aphasia performed comparably to healthy controls. Grey matter associations with task performance were identified in anterior temporal, medial and lateral orbitofrontal cortices, previously implicated in computing diverse biological and non-biological rules and rewards. The processing of musical rules and reward distils cognitive and neuroanatomical mechanisms relevant to complex socio-emotional dysfunction in major dementias