Gated Mode Superconducting Nanowire Single Photon Detectors

Single Photon Detectors (SPD) are fundamental to quantum optics and quantum information. Superconducting Nanowire SPDs (SNSPD) [1] provide high performance in terms of quantum efficiency (QE), dark count rate (DCR) and timing jitter [2], but have limited maximum count rate (MCR) when operated as a free-running mode (FM) detector [3, 4]. However, high count rates are needed for many applications like quantum computing [5] and communication [6], and laser ranging [7]. Here we report the first operation of SNSPDs in a gated mode (GM) that exploits a single photon triggered latching phenomenon to detect photons. We demonstrate operation of a large active area single element GM-SNSPD at 625MHz, one order of magnitude faster than its FM counterpart. Contrary to FM-SNSPDs, the MCR in GM can be pushed to GHz range without a compromise on the active area or QE, while reducing the DCR

A superconducting-nanowire 3-terminal electronic device

In existing superconducting electronic systems, Josephson junctions play a central role in processing and transmitting small-amplitude electrical signals. However, Josephson-junction-based devices have a number of limitations including: (1) sensitivity to magnetic fields, (2) limited gain, (3) inability to drive large impedances, and (4) difficulty in controlling the junction critical current (which depends sensitively on sub-Angstrom-scale thickness variation of the tunneling barrier). Here we present a nanowire-based superconducting electronic device, which we call the nanocryotron (nTron), that does not rely on Josephson junctions and can be patterned from a single thin film of superconducting material with conventional electron-beam lithography. The nTron is a 3-terminal, T-shaped planar device with a gain of ~20 that is capable of driving impedances of more than 100 k{\Omega}, and operates in typical ambient magnetic fields at temperatures of 4.2K. The device uses a localized, Joule-heated hotspot formed in the gate to modulate current flow in a perpendicular superconducting channel. We have characterized the nTron, matched it to a theoretical framework, and applied it both as a digital logic element in a half-adder circuit, and as a digital amplifier for superconducting nanowire single-photon detectors pulses. The nTron has immediate applications in classical and quantum communications, photon sensing and astronomy, and its performance characteristics make it compatible with existing superconducting technologies. Furthermore, because the hotspot effect occurs in all known superconductors, we expect the design to be extensible to other materials, providing a path to digital logic, switching, and amplification in high-temperature superconductors

Superconducting nano-strip particle detectors

We review progress in the development and applications of superconducting nano-strip particle detectors. Particle detectors based on superconducting nano-strips stem from the parent devices developed for single photon detection (SSPD) and share with them ultra-fast response times (sub-nanosecond) and the ability to operate at a relatively high temperature (2–5 K) compared with other cryogenic detectors. SSPDs have been used in the detection of electrons, neutral and charged ions, and biological macromolecules; nevertheless, the development of superconducting nano-strip particle detectors has mainly been driven by their use in time-of-flight mass spectrometers (TOF-MSs) where the goal of 100% efficiency at large mass values can be achieved. Special emphasis will be given to this case, reporting on the great progress which has been achieved and which permits us to overcome the limitations of existing mass spectrometers represented by low detection efficiency at large masses and charge/mass ambiguity. Furthermore, such progress could represent a breakthrough in the field. In this review article we will introduce the device concept and detection principle, stressing the peculiarities of the nano-strip particle detector as well as its similarities with photon detectors. The development of parallel strip configuration is introduced and extensively discussed, since it has contributed to the significant progress of TOF-MS applications

Superconducting nanowire single-photon detectors: physics and applications

Single-photon detectors based on superconducting nanowires (SSPDs or SNSPDs) have rapidly emerged as a highly promising photon-counting technology for infrared wavelengths. These devices offer high efficiency, low dark counts and excellent timing resolution. In this review, we consider the basic SNSPD operating principle and models of device behaviour. We give an overview of the evolution of SNSPD device design and the improvements in performance which have been achieved. We also evaluate device limitations and noise mechanisms. We survey practical refrigeration technologies and optical coupling schemes for SNSPDs. Finally we summarize promising application areas, ranging from quantum cryptography to remote sensing. Our goal is to capture a detailed snapshot of an emerging superconducting detector technology on the threshold of maturity.Comment: 27 pages, 5 figures, Review article preprint versio

Design and Analysis of Rhesus Cytomegalovirus IL-10 Mutants as a Model for Novel Vaccines against Human Cytomegalovirus

Human cytomegalovirus (HCMV) expresses a viral ortholog (CMVIL-10) of human cellular interleukin-10 (cIL-10). Despite only ∼26% amino acid sequence identity, CMVIL-10 exhibits comparable immunosuppressive activity with cIL-10, attenuates HCMV antiviral immune responses, and contributes to lifelong persistence within infected hosts. The low sequence identity between CMVIL-10 and cIL-10 suggests vaccination with CMVIL-10 may generate antibodies that specifically neutralize CMVIL-10 biological activity, but not the cellular cytokine, cIL-10. However, immunization with functional CMVIL-10 might be detrimental to the host because of its immunosuppressive properties.Structural biology was used to engineer biologically inactive mutants of CMVIL-10 that would, upon vaccination, elicit a potent immune response to the wild-type viral cytokine. To test the designed proteins, the mutations were incorporated into the rhesus cytomegalovirus (RhCMV) ortholog of CMVIL-10 (RhCMVIL-10) and used to vaccinate RhCMV-infected rhesus macaques. Immunization with the inactive RhCMVIL-10 mutants stimulated antibodies against wild-type RhCMVIL-10 that neutralized its biological activity, but did not cross-react with rhesus cellular IL-10.This study demonstrates an immunization strategy to neutralize RhCMVIL-10 biological activity using non-functional RhCMVIL-10 antigens. The results provide the methodology for targeting CMVIL-10 in vaccine, and therapeutic strategies, to nullify HCMV's ability to (1) skew innate and adaptive immunity, (2) disseminate from the site of primary mucosal infection, and (3) establish a lifelong persistent infection

Cure of Chronic Viral Infection and Virus-Induced Type 1 Diabetes by Neutralizing Antibodies

The use of neutralizing antibodies is one of the most successful methods to interfere with receptor–ligand interactions in vivo. In particular blockade of soluble inflammatory mediators or their corresponding cellular receptors was proven an effective way to regulate inflammation and/or prevent its negative consequences. However, one problem that comes along with an effective neutralization of inflammatory mediators is the general systemic immunomodulatory effect. It is, therefore, important to design a treatment regimen in a way to strike at the right place and at the right time in order to achieve maximal effects with minimal duration of immunosuppression or hyperactivation. In this review, we reflect on two examples of how short time administration of such neutralizing antibodies can block two distinct inflammatory consequences of viral infection. First, we review recent findings that blockade of IL-10/IL-10R interaction can resolve chronic viral infection and second, we reflect on how neutralization of the chemokine CXCL10 can abrogate virus-induced type 1 diabetes

Pre-Existing Adenovirus Immunity Modifies a Complex Mixed Th1 and Th2 Cytokine Response to an Ad5/HIV-1 Vaccine Candidate in Humans

The results of the recent Step Study highlight a need to clarify the effects of pre-existing natural immunity to a vaccine vector on vaccine-induced T-cell responses. To investigate this interaction, we examined the relationship between pre-existing Ad5 immunity and T-cell cytokine response profiles in healthy, HIV-uninfected recipients of MRKAd5 HIV-1 gag vaccine (HVTN 050, ClinicalTrials.gov #NCT00849732). Participants were grouped by baseline Ad5 neutralizing antibody titer as either Ad5-seronegative (titer ≤18; n = 36) or Ad5-seropositive (titer >200; n = 34). Samples from vaccine recipients were analyzed for immune responses to either HIV-1 Gag peptide pools or Ad5 empty vector using an ex vivo assay that measures thirty cytokines in the absence of long-term culture. The overall profiles of cytokine responses to Gag and Ad5 had similar combinations of induced Th1- and Th2-type cytokines, including IFN-γ, IL-2, TNF-α, IP-10, IL-13, and IL-10, although the Ad5-specific responses were uniformly higher than the Gag-specific responses (p<0.0001 for 9 out of 11 significantly expressed analytes). At the peak response time point, PBMC from Ad5-seronegative vaccinees secreted significantly more IP-10 in response to Gag (p = 0.008), and significantly more IP-10 (p = 0.0009), IL-2 (p = 0.006) and IL-10 (p = 0.05) in response to Ad5 empty vector than PBMC from Ad5-seropositive vaccinees. Additionally, similar responses to the Ad5 vector prior to vaccination were observed in almost all subjects, regardless of Ad5 neutralizing antibody status, and the levels of secreted IFN-γ, IL-10, IL-1Ra and GM-CSF were blunted following vaccination. The cytokine response profile of Gag-specific T cells mirrored the Ad5-specific response present in all subjects before vaccination, and included a number of Th1- and Th2-associated cytokines not routinely assessed in current vaccine trials, such as IP-10, IL-10, IL-13, and GM-CSF. Together, these results suggest that vector-specific humoral responses may reduce vaccine-induced T-cell responses by previously undetected mechanisms

A Temporal Role Of Type I Interferon Signaling in CD8+ T Cell Maturation during Acute West Nile Virus Infection

A genetic absence of the common IFN- α/β signaling receptor (IFNAR) in mice is associated with enhanced viral replication and altered adaptive immune responses. However, analysis of IFNAR-/- mice is limited for studying the functions of type I IFN at discrete stages of viral infection. To define the temporal functions of type I IFN signaling in the context of infection by West Nile virus (WNV), we treated mice with MAR1-5A3, a neutralizing, non cell-depleting anti-IFNAR antibody. Inhibition of type I IFN signaling at or before day 2 after infection was associated with markedly enhanced viral burden, whereas treatment at day 4 had substantially less effect on WNV dissemination. While antibody treatment prior to infection resulted in massive expansion of virus-specific CD8+ T cells, blockade of type I IFN signaling starting at day 4 induced dysfunctional CD8+ T cells with depressed cytokine responses and expression of phenotypic markers suggesting exhaustion. Thus, only the later maturation phase of anti-WNV CD8+ T cell development requires type I IFN signaling. WNV infection experiments in BATF3-/- mice, which lack CD8-α dendritic cells and have impaired priming due to inefficient antigen cross-presentation, revealed a similar effect of blocking IFN signaling on CD8+ T cell maturation. Collectively, our results suggest that cell non-autonomous type I IFN signaling shapes maturation of antiviral CD8+ T cell response at a stage distinct from the initial priming event

Immunosuppression during Acute Infection with Foot-and-Mouth Disease Virus in Swine Is Mediated by IL-10

Foot-and-mouth disease virus (FMDV) is one of the most contagious animal viruses, causing a devastating disease in cloven-hoofed animals with enormous economic consequences. Identification of the different parameters involved in the immune response elicited against FMDV remains unclear, and it is fundamental the understanding of such parameters before effective control measures can be put in place. In the present study, we show that interleukin-10 (IL-10) production by dendritic cells (DCs) is drastically increased during acute infection with FMDV in swine. In vitro blockade of IL-10 with a neutralizing antibody against porcine IL-10 restores T cell activation by DCs. Additionally, we describe that FMDV infects DC precursors and interferes with DC maturation and antigen presentation capacity. Thus, we propose a new mechanism of virus immunity in which a non-persistent virus, FMDV, induces immunosuppression by an increment in the production of IL-10, which in turn, reduces T cell function. This reduction of T cell activity may result in a more potent induction of neutralizing antibody responses, clearing the viral infection