Perspective using cross-species vaccination approaches to counter emerging infectious diseases

Since the initial use of vaccination in the eighteenth century, our understanding of human and animal immunology has greatly advanced and a wide range of vaccine technologies and delivery systems have been developed. The COVID-19 pandemic response leveraged these innovations to enable rapid development of candidate vaccines within weeks of the viral genetic sequence being made available. The development of vaccines to tackle emerging infectious diseases is a priority for the World Health Organization and other global entities. More than 70% of emerging infectious diseases are acquired from animals, with some causing illness and death in both humans and the respective animal host. Yet the study of critical host–pathogen interactions and the underlying immune mechanisms to inform the development of vaccines for their control is traditionally done in medical and veterinary immunology ‘silos’. In this Perspective, we highlight a ‘One Health vaccinology’ approach and discuss some key areas of synergy in human and veterinary vaccinology that could be exploited to accelerate the development of effective vaccines against these shared health threats

Apparatus for simultaneous DLS-SANS investigations of dynamics and structure in soft matter

Dynamic Light Scattering (DLS) and Small-Angle Neutron Scattering (SANS) are two key tools with which to probe the dynamic and static structure factor, respectively, in soft matter. Usually DLS and SANS measurements are performed separately, in different laboratories, on different samples and at different times. However, this methodology has particular disadvantages for a large variety of soft materials which exhibit high sensitivity to small changes in fundamental parameters such as waiting times, concentration, pH, ionic strength, etc. Here we report on a new portable DLS-SANS apparatus that allows one to simultaneously measure both the microscopic dynamics (through DLS) and the static structure (through SANS) on the same sample. The apparatus has been constructed as a collaboration between two laboratories, each an expert in one of the scattering methods, and was commissioned on the \textit{LOQ} and \textit{ZOOM} SANS instruments at the ISIS Pulsed Neutron \& Muon Source, U.K

Report on Selected Standardization Activities of the IEEE BASC and of the ATM Forum

This document describes the standardization activities which were performed during the first year period of the joint project named ﲁ Standardization and Research Project on an ATM/B-ISDN Switching Fabric System that is being jointly performed by Protocol Engineering Center (PEC) of Electronics and Telecommunications Research Institute (ETRI), Institute for Systems Research (ISR) of the University of Maryland at College Park (UMCP) and Modacom Co., Ltd. These standardization activities are related to the IEEE Bus Architecture Standards Committee (BASC) meetings and ATM Forum Meetings. This document also provides the general information about the IEEE Standards meetings and ATM Forum Standards meetings.<P

ATM/LAN Access Switch (ALAX): System Architecture

This document contains the hardware information for the ATM LAN Access Switch (ALAX) that was done as a collaborative research and development effort by the Institute for Systems Research at the University of Maryland, College Park, Protocol Engineering Center in Electronics and Telecommunications Research Institute, and Modacom Co., Ltd. of Korea.<P

OPNET Simulation Model of the ALAX

When this project wsa undertaken, the ALAX system was designed but was not built yet. Because it was too complicated for us to easily predict the detailed behavior of the system before we built it, we decided to use the OPNET simulation to evaluate the ALAX system before it was built. The performance of the ALAX could be predicted by analyzing the results of the OPNET simulation, and the optimal architecture of the ALAX developed by devising the proper number of transputers and the proper packet buffer size of the ALAX system.<P

Compensatory Paracrine Mechanisms That Define The Urothelial Response to Injury in Partial Bladder Outlet Obstruction

Diseases and conditions affecting the lower urinary tract are a leading cause of dysfunctional sexual health, incontinence, infection, and kidney failure. The growth, differentiation, and repair of the bladder&#39;s epithelial lining are regulated, in part, by fibroblast growth factor (FGF)-7 and -10 via a paracrine cascade originating in the mesenchyme (lamina propria) and targeting the receptor for FGF-7 and -10 within the transitional epithelium (urothelium). The FGF-7 gene is located at the 15q15-q21.1 locus on chromosome 15 and four exons generate a 3.852-kb mRNA. Five duplicated FGF-7 gene sequences that localized to chromosome 9 were predicted not to generate functional protein products, thus validating the use of FGF-7-null mice as an experimental model. Recombinant FGF-7 and -10 induced proliferation of human urothelial cells in vitro and transitional epithelium of wild-type and FGF-7-null mice in vivo.To determine the extent that induction of urothelial cell proliferation during the bladder response to injury is dependent on FGF-7, an animal model of partial bladder outlet obstruction was developed. Unbiased stereology was used to measure the percentage of proliferating urothelial cells between obstructed groups of wild-type and FGF-7-null mice. The stereological analysis indicated that a statistical significant difference did not exist between the two groups, suggesting that FGF-7 is not essential for urothelial cell proliferation in response to partial outlet obstruction. In contrast, a significant increase in FGF-10 expression was observed in the obstructed FGF-7-null group, indicating that the compensatory pathway that functions in this model results in urothelial repair

ALAX- A P1355-Based Architecture for An ATM LAN Access Switch, with Application to ATM Onboard Switching

We draw attention to the new IEEE P1355 Standard for Heterogeneous InterConnect as a possible platform to support several onboard processing functions, including onboard communications and onboard ATM switching. The main features of IEEE P1355 are illustrated through a discussion of the basic principles and protocol architecture of ALAX, the ATM LAN Access Switch, currently under design in the Laboratory for Advanced Switching Technologies at the University of Maryland, College Park

Exome sequencing of Finnish isolates enhances rare-variant association power.

Exome-sequencing studies have generally been underpowered to identify deleterious alleles with a large effect on complex traits as such alleles are mostly rare. Because the population of northern and eastern Finland has expanded considerably and in isolation following a series of bottlenecks, individuals of these populations have numerous deleterious alleles at a relatively high frequency. Here, using exome sequencing of nearly 20,000 individuals from these regions, we investigate the role of rare coding variants in clinically relevant quantitative cardiometabolic traits. Exome-wide association studies for 64 quantitative traits identified 26 newly associated deleterious alleles. Of these 26 alleles, 19 are either unique to or more than 20 times more frequent in Finnish individuals than in other Europeans and show geographical clustering comparable to Mendelian disease mutations that are characteristic of the Finnish population. We estimate that sequencing studies of populations without this unique history would require hundreds of thousands to millions of participants to achieve comparable association power

Magnitude and kinetics of T cell and antibody responses during H1N1pdm09 infection in inbred Babraham pigs and outbred pigs

We have used the pig, a large natural host animal for influenza with many physiological similarities to humans, to characterize αβ, γδ T cell and antibody (Ab) immune responses to the 2009 pandemic H1N1 virus infection. We evaluated the kinetic of virus infection and associated response in inbred Babraham pigs with identical MHC (Swine Leucocyte Antigen) and compared them to commercial outbred animals. High level of nasal virus shedding continued up to days 4 to 5 post infection followed by a steep decline and clearance of virus by day 9. Adaptive T cell and Ab responses were detectable from days 5 to 6 post infection reaching a peak at 9 to 14 days. γδ T cells produced cytokines ex vivo at day 2 post infection, while virus reactive IFNγ producing γδ T cells were detected from day 7 post infection. Analysis of NP tetramer specific and virus specific CD8 and CD4 T cells in blood, lung, lung draining lymph nodes, and broncho-alveolar lavage (BAL) showed clear differences in cytokine production between these tissues. BAL contained the most highly activated CD8, CD4, and γδ T cells producing large amounts of cytokines, which likely contribute to elimination of virus. The weak response in blood did not reflect the powerful local lung immune responses. The immune response in the Babraham pig following H1N1pdm09 influenza infection was comparable to that of outbred animals. The ability to utilize these two swine models together will provide unparalleled power to analyze immune responses to influenza

Coevolution between a Family of Parasite Virulence Effectors and a Class of LINE-1 Retrotransposons

Parasites are able to evolve rapidly and overcome host defense mechanisms, but the molecular basis of this adaptation is poorly understood. Powdery mildew fungi (Erysiphales, Ascomycota) are obligate biotrophic parasites infecting nearly 10,000 plant genera. They obtain their nutrients from host plants through specialized feeding structures known as haustoria. We previously identified the AVRk1 powdery mildew-specific gene family encoding effectors that contribute to the successful establishment of haustoria. Here, we report the extensive proliferation of the AVRk1 gene family throughout the genome of B. graminis, with sequences diverging in formae speciales adapted to infect different hosts. Also, importantly, we have discovered that the effectors have coevolved with a particular family of LINE-1 retrotransposons, named TE1a. The coevolution of these two entities indicates a mutual benefit to the association, which could ultimately contribute to parasite adaptation and success. We propose that the association would benefit 1) the powdery mildew fungus, by providing a mechanism for amplifying and diversifying effectors and 2) the associated retrotransposons, by providing a basis for their maintenance through selection in the fungal genome