Quantum Transpiler Optimization: On the Development, Implementation, and Use of a Quantum Research Testbed

Quantum computing research is at the cusp of a paradigm shift. As the complexity of quantum systems increases, so does the complexity of research procedures for creating and testing layers of the quantum software stack. However, the tools used to perform these tasks have not experienced the increase in capability required to effectively handle the development burdens involved. This case is made particularly clear in the context of IBM QX Transpiler optimization algorithms and functions. IBM QX systems use the Qiskit library to create, transform, and execute quantum circuits. As coherence times and hardware qubit counts increase and qubit topologies become more complex, so does orchestration of qubit mapping and qubit state movement across these topologies. The transpiler framework used to create and test improved algorithms has not kept pace. A testbed is proposed to provide abstractions to create and test transpiler routines. The development process is analyzed and implemented, from design principles through requirements analysis and verification testing. Additionally, limitations of existing transpiler algorithms are identified and initial results are provided that suggest more effective algorithms for qubit mapping and state movement

Widespread recombination, reassortment, and transmission of unbalanced compound viral genotypes in natural arenavirus infections.

Arenaviruses are one of the largest families of human hemorrhagic fever viruses and are known to infect both mammals and snakes. Arenaviruses package a large (L) and small (S) genome segment in their virions. For segmented RNA viruses like these, novel genotypes can be generated through mutation, recombination, and reassortment. Although it is believed that an ancient recombination event led to the emergence of a new lineage of mammalian arenaviruses, neither recombination nor reassortment has been definitively documented in natural arenavirus infections. Here, we used metagenomic sequencing to survey the viral diversity present in captive arenavirus-infected snakes. From 48 infected animals, we determined the complete or near complete sequence of 210 genome segments that grouped into 23 L and 11 S genotypes. The majority of snakes were multiply infected, with up to 4 distinct S and 11 distinct L segment genotypes in individual animals. This S/L imbalance was typical: in all cases intrahost L segment genotypes outnumbered S genotypes, and a particular S segment genotype dominated in individual animals and at a population level. We corroborated sequencing results by qRT-PCR and virus isolation, and isolates replicated as ensembles in culture. Numerous instances of recombination and reassortment were detected, including recombinant segments with unusual organizations featuring 2 intergenic regions and superfluous content, which were capable of stable replication and transmission despite their atypical structures. Overall, this represents intrahost diversity of an extent and form that goes well beyond what has been observed for arenaviruses or for viruses in general. This diversity can be plausibly attributed to the captive intermingling of sub-clinically infected wild-caught snakes. Thus, beyond providing a unique opportunity to study arenavirus evolution and adaptation, these findings allow the investigation of unintended anthropogenic impacts on viral ecology, diversity, and disease potential

Incidence of Plasmodium falciparum malaria infection in 6-month to 45-year-olds on selected areas of Bioko Island, Equatorial Guinea

BACKGROUND: Extensive malaria control measures have been implemented on Bioko Island, Equatorial Guinea over the past 16 years, reducing parasite prevalence and malaria-related morbidity and mortality, but without achieving elimination. Malaria vaccines offer hope for reducing the burden to zero. Three phase 1/2 studies have been conducted successfully on Bioko Island to evaluate the safety and efficacy of whole Plasmodium falciparum (Pf) sporozoite (SPZ) malaria vaccines. A large, pivotal trial of the safety and efficacy of the radiation-attenuated Sanaria((R)) PfSPZ Vaccine against P. falciparum is planned for 2022. This study assessed the incidence of malaria at the phase 3 study site and characterized the influence of socio-demographic factors on the burden of malaria to guide trial design. METHODS: A cohort of 240 randomly selected individuals aged 6 months to 45 years from selected areas of North Bioko Province, Bioko Island, was followed for 24 weeks after clearance of parasitaemia. Assessment of clinical presentation consistent with malaria and thick blood smears were performed every 2 weeks. Incidence of first and multiple malaria infections per person-time of follow-up was estimated, compared between age groups, and examined for associated socio-demographic risk factors. RESULTS: There were 58 malaria infection episodes observed during the follow up period, including 47 first and 11 repeat infections. The incidence of malaria was 0.25 [95% CI (0.19, 0.32)] and of first malaria was 0.23 [95% CI (0.17, 0.30)] per person per 24 weeks (0.22 in 6-59-month-olds, 0.26 in 5-17-year-olds, 0.20 in 18-45-year-olds). Incidence of first malaria with symptoms was 0.13 [95% CI (0.09, 0.19)] per person per 24 weeks (0.16 in 6-59-month-olds, 0.10 in 5-17-year-olds, 0.11 in 18-45-year-olds). Multivariate assessment showed that study area, gender, malaria positivity at screening, and household socioeconomic status independently predicted the observed incidence of malaria. CONCLUSION: Despite intensive malaria control efforts on Bioko Island, local transmission remains and is spread evenly throughout age groups. These incidence rates indicate moderate malaria transmission which may be sufficient to support future larger trials of PfSPZ Vaccine. The long-term goal is to conduct mass vaccination programmes to halt transmission and eliminate P. falciparum malaria

Concerning trends in allopathic medical school faculty rank for Indigenous people: 2014–2016

Background: Trends in faculty rank according to racial and ethnic composition have not been reviewed in over a decade. Objective: To study trends in faculty rank according to racial and ethnicity with a specific focus on Indigenous faculty, which has been understudied. Methods: Data from the Association of American Medical Colleges’ Faculty Administrative Management Online User System was used to study trends in race/ethnicity faculty composition and rank between 2014 and 2016, which included information on 481,753 faculty members from 141 US allopathic medical schools. Results: The majority of medical school faculty were White, 62.4% (n = 300,642). Asian composition represented 14.7% (n = 70,647). Hispanic, Latino, or of Spanish Origin; Multiple Race-Hispanic; Multiple Race-Non-Hispanic; and Black/African American faculty represented 2.2%, 2.3%, 3.0%, and 3.0%, respectively. Indigenous faculty members, defined as American Indian/Alaska Native (AIAN), Native Hawaiian or Other Pacific Islander (NHPI), represented the smallest percentage of faculty at 0.11% and 0.18%, respectively. White faculty predominated the full professor rank at 27.5% in 2016 with a slight decrease between 2014 and 2016. Indigenous faculty represented the lowest percent of full professor faculty at 5.2% in 2016 for AIAN faculty and a decline from 4.6% to 1.6% between 2014 and 2016 for NHPI faculty (p < 0.001). Conclusions: While US medical school faculty are becoming more racially and ethnically diverse, representation of AIAN faculty is not improving and is decreasing significantly among NHPI faculty. Little progress has been made in eliminating health disparities among Indigenous people. Diversifying the medical workforce could better meet the needs of communities that historically and currently experience a disproportionate disease burden

Immunization of malaria pre-exposed volunteers with PfSPZ Vaccine elicits long-lived IgM invasion-inhibitory and complement-fixing antibodies

The assessment of antibody responses after immunization with radiation-attenuated, aseptic, purified, cryopreserved Plasmodium falciparum sporozoites (Sanaria PfSPZ Vaccine) has focused on IgG isotype antibodies. Here, we aimed to investigate if P. falciparum sporozoite binding and invasion-inhibitory IgM antibodies are induced following immunization of malaria-preexposed volunteers with PfSPZ Vaccine.; Using serum from volunteers immunized with PfSPZ, we measured vaccine-induced IgG and IgM antibodies to P. falciparum circumsporozoite protein (PfCSP) via ELISA. Function of this serum as well as IgM antibody fractions was measured via in vitro in an inhibition of sporozoite invasion assay. These IgM antibody fractions were also measured for binding to sporozoites by immunofluorescence assay and complement fixation on whole sporozoites.; We found that in addition to anti-PfCSP IgG, malaria-preexposed volunteers developed anti-PfCSP IgM antibodies after immunization with PfSPZ Vaccine and that these IgM antibodies inhibited P. falciparum sporozoite invasion of hepatocytes in vitro. These IgM plasma fractions also fixed complement to whole P. falciparum sporozoites.; This is the first finding that PfCSP and P. falciparum sporozoite-binding IgM antibodies are induced following immunization of PfSPZ Vaccine in malaria-preexposed individuals and that IgM antibodies can inhibit P. falciparum sporozoite invasion into hepatocytes in vitro and fix complement on sporozoites. These findings indicate that the immunological assessment of PfSPZ Vaccine-induced antibody responses could be more sensitive if they include parasite-specific IgM in addition to IgG antibodies.; NCT02132299

The Candidate Blood-stage Malaria Vaccine P27A Induces a Robust Humoral Response in a Fast Track to the Field Phase 1 Trial in Exposed and Nonexposed Volunteers.

P27A is an unstructured 104mer synthetic peptide from Plasmodium falciparum trophozoite exported protein 1 (TEX1), the target of human antibodies inhibiting parasite growth. The present project aimed at evaluating the safety and immunogenicity of P27A peptide vaccine in malaria-nonexposed European and malaria-exposed African adults. This study was designed as a staggered, fast-track, randomized, antigen and adjuvant dose-finding, multicenter phase 1a/1b trial, conducted in Switzerland and Tanzania. P27A antigen (10 or 50 μg), adjuvanted with Alhydrogel or glucopyranosil lipid adjuvant stable emulsion (GLA-SE; 2.5 or 5 μg), or control rabies vaccine (Verorab) were administered intramuscularly to 16 malaria-nonexposed and 40 malaria-exposed subjects on days 0, 28, and 56. Local and systemic adverse events (AEs) as well as humoral and cellular immune responses were assessed after each injection and during the 34-week follow-up. Most AEs were mild to moderate and resolved completely within 48 hours. Systemic AEs were more frequent in the formulation with alum as compared to GLA-SE, whereas local AEs were more frequent after GLA-SE. No serious AEs occurred. Supported by a mixed Th1/Th2 cell-mediated immunity, P27A induced a marked specific antibody response able to recognize TEX1 in infected erythrocytes and to inhibit parasite growth through an antibody-dependent cellular inhibition mechanism. Incidence of AEs and antibody responses were significantly lower in malaria-exposed Tanzanian subjects than in nonexposed European subjects. The candidate vaccine P27A was safe and induced a particularly robust immunogenic response in combination with GLA-SE. This formulation should be considered for future efficacy trials. NCT01949909, PACTR201310000683408

Virus populations replicate as stable ensembles in culture: (A) Liver homogenate from snake #38 was applied to cultures of JK cells and replication was monitored by measuring supernatant viral RNA levels using qRT-PCR and genotype-specific primers.

<p>Levels of distinct S and L genotypes detected are indicated and are normalized to the amount of S RNA detected in the first time point. Points and error bars represent mean and standard deviation of two independent experiments. <b>(B)</b> As in (A), but a liver homogenate from snake #47 was used as inoculum. <b>(C)</b> The 2xIGR L4 segment detected in snake #47 replicates stably in culture. Same experiment as (B), but qRT-PCR used primers that targeted two different regions of the L4 segment as depicted in the inset cartoon.</p