The 2013–2016 West Africa EBOV epidemic was the biggest EBOV outbreak to date. An analysis of virus-specific CD8+ T-cell immunity in 30 survivors showed that 26 of those individuals had a CD8+ ...response to at least one EBOV protein. The dominant response (25/26 subjects) was specific to the EBOV nucleocapsid protein (NP). It has been suggested that epitopes on the EBOV NP could form an important part of an effective T-cell vaccine for Ebola Zaire. We show that a 9-amino-acid peptide NP44-52 (YQVNNLEEI) located in a conserved region of EBOV NP provides protection against morbidity and mortality after mouse adapted EBOV challenge. A single vaccination in a C57BL/6 mouse using an adjuvanted microsphere peptide vaccine formulation containing NP44-52 is enough to confer immunity in mice. Our work suggests that a peptide vaccine based on CD8+ T-cell immunity in EBOV survivors is conceptually sound and feasible. Nucleocapsid proteins within SARS-CoV-2 contain multiple Class I epitopes with predicted HLA restrictions consistent with broad population coverage. A similar approach to a CTL vaccine design may be possible for that virus.
We reduce the required trusted computing base for direct recording electronic (DRE) voting machines with a design based on trusted platform modules (TPMs). Our approach ensures election data ...integrity by binding the voter's choices with the presented ballot using a platform vote ballot (PVB) signature key managed by the TPM. The TPM can use the PVB key only when static measurements of the software reflect an uncompromised state and when a precinct judge enters a special password revealed on election day. Using the PVB with the TPM can expose authorized software, ballot modifications, vote tampering, and creation of fake election records early in the election process. Our protocol places trust in tamper resistant hardware, not in mutable system software. Although we are not the first to suggest using TPMs in voting, we are the first to provide a detailed engineering protocol that binds the voter choices with the presented ballot and uses the TPM to enforce election policy. We present the protocol, architecture, assumptions, and security arguments in enough detail to support further analysis or implementation.
Scantegrity II is an enhancement for existing paper ballot systems. It allows voters to verify election integrity - from their selections on the ballot all the way to the final tally - by noting ...codes and checking for them online. Voters mark Scantegrity II ballots just as with conventional optical scan, but using a special ballot marking pen. Marking a selection with this pen makes legible an otherwise invisible preprinted confirmation code. Confirmation codes are independent and random for each potential selection on each ballot. To verify that their individual votes are recorded correctly, voters can look up their ballot serial numbers online and verify that their confirmation codes are posted correctly. The confirmation codes do not allow voters to prove how they voted. However, the confirmation codes constitute convincing evidence of error or malfeasance in the event that incorrect codes are posted online. Correctness of the final tally with respect to the published codes is proven by election officials in a manner that can be verified by any interested party. Thus, compromise of either ballot chain of custody or the software systems cannot undetectably affect election integrity. Scantegrity II has been implemented and tested in small elections in which ballots were scanned either at the polling place or centrally. Preparations for its use in a public sector election have commenced.
The continuing requirement for corporate right sizing demand's businesses ensure their security structure minimizes costs while maximizing efficiency and effectiveness. In large campus organizations ...with a security protective force and multiple security systems, the advance of security systems technologies and telecommunication technologies enable massive reduction in the manpower required to monitor the command and control of the systems through the consolidation of resources, the automation and integration of the security systems, and process re-engineering. This paper presents a business case and user experience in the development and implementation of a centralized Communication Center (ComCenter) within a large geographically dispersed multiple building multi-campus organization. The centralized ComCenter replaces three large geographically located Communication Centers and several small monitoring locations throughout the metropolitan area. Through process reengineering, the protective force required to monitor the process is reduced in half, a decrease of more than forty-nine (49) man years of effort. The consolidation replaced multiple independent intrusion detection systems with a single system. The ComCenter has three identical integrated operator consoles with access to the Intrusion Detection System, Closed Circuit Television (CCTV) system, Emergency Services (911), Radio Communications, Access Control, and National Crime Information Center information. The command and control of each of the security systems is provided within a computing platform using graphical user interfaces. The ComCenter process monitors greater than five (5) million square feet of corporate space and facilities using greater than 4,000 individual intrusion detection devices and greater than 300 CCTV cameras. The CCTV camera monitoring and control is provided on the operator console screen and allows forwarding via a worldwide video teleconferencing system. The effects of the large scale re-engineering and consolidation effort upon the vendors, the security force, and the organization's security infrastructure shall be presented.
Survivin (BIRC5) is a tumor-associated antigen (TAA) overexpressed in various tumors but present at low to undetectable levels in normal tissue. Survivin is known to have a high expression in breast ...cancer (e.g., Ductal Carcinoma in situ (DCIS) and triple negative breast cancer). Previous studies have not compared survivin expression levels in DCIS tumor samples to levels in adjacent, normal breast tissue from the same patient. To ensure the effective use of survivin as a target for T cell immunotherapy of breast cancer, it is essential to ascertain the varying levels of survivin expression between DCIS tumor tissue samples and the adjacent normal breast tissue taken from the same patient simultaneously. Next-generation sequencing of RNA (RNA-seq) in normal breast tissue and tumor breast tissue from five women presenting with DCIS for lumpectomy was used to identify sequence variation and expression levels of survivin. The identity of both tumor and adjacent normal tissue samples were corroborated by histopathology. Survivin was overexpressed in human breast tissue tumor samples relative to the corresponding adjacent human normal breast tissue. Wild-type survivin transcripts were the predominant species identified in all tumor tissue sequenced. This study demonstrates upregulated expression of wild type survivin in DCIS tumor tissue versus normal breast tissue taken from the same patient at the same time, and provides evidence that developing selective cytotoxic T lymphocyte (CTL) immunotherapy for DCIS targeting survivin warrants further study.
A mutation analysis of SARS-CoV-2 genomes collected around the world sorted by sequence, date, geographic location, and species has revealed a large number of variants from the initial reference ...sequence in Wuhan. This analysis also reveals that humans infected with SARS-CoV-2 have infected mink populations in the Netherlands, Denmark, United States, and Canada. In these animals, a small set of mutations in the spike protein receptor binding domain (RBD), often occurring in specific combinations, has transferred back into humans. The viral genomic mutations in minks observed in the Netherlands and Denmark show the potential for new mutations on the SARS-CoV-2 spike protein RBD to be introduced into humans by zoonotic transfer. Our data suggests that close attention to viral transfer from humans to farm animals and pets will be required to prevent build-up of a viral reservoir for potential future zoonotic transfer.
•SARS-CoV-2 spike protein mutations have shown a pattern of zoonotic transfer.•Pairing of certain spike mutations allows for viral infectivity between species.•Mutations via zoonosis in Europe have also appeared independently in the US.•Mutations assisted through zoonotic transfer could affect pharmaceutical intervention.•Sequencing efforts for a pandemic-causing virus should include a wide range of host species.
Security in today's government and commercial environments is changing. The willingness to provide manpower against security threats is diminishing. Risk management is preferred to risk avoidance. In ...order for management to ensure that the appropriate security is provided while downsizing or right sizing protective services and other security personnel, automation of security technologies is a necessity. Several manpower intensive tasks and processes are: facilities access control, issuance of staff and visitor badges, provision of information for visitors, access control to interior facilities, and the issuance of office keys. Reduction of the required manning for these processes is enabled though the automation and integration of various security technologies including biometric identification systems. This paper provides a background on manpower intensive tasks and processes, security technologies that may be employed within them, resource reduction capabilities, and a customer's experience with the use of the technologies within a large Government environment.
A triple negative breast cancer model using the murine 4T1 tumor cell line was used to explore the efficacy of an adjuvanted survivin peptide microparticle vaccine using tumor growth as the outcome ...metric. We first performed tumor cell dose titration studies to determine a tumor cell dose that resulted in sufficient tumor takes but allowed multiple serial measurements of tumor volumes, yet with minimal morbidity/mortality within the study period. Later, in a second cohort of mice, the survivin peptide microparticle vaccine was administered via intraperitoneal injection at the study start with a second dose given 14 days later. An orthotopic injection of 4T1 cells into the mammary tissue was performed on the same day as the administration of the second vaccine dose. The mice were followed for up to 41 days with subcutaneous measurements of tumor volume made every 3-4 days. Vaccination with survivin peptides was associated with a peptide antigen-specific gamma interferon enzyme-linked immunosorbent spot response in the murine splenocyte population but was absent from the control microparticle group. At the end of the study, we found that vaccination with adjuvanted survivin peptide microparticles resulted in statistically significant slower primary tumor growth rates in BALB/c mice challenged with 4T1 cells relative to the control peptideless vaccination group. These studies suggest that T cell immunotherapy specifically targeting survivin might be an applicable neoadjuvant immunotherapy therapy for triple negative breast cancer. More preclinical studies and clinical trials are needed to explore this concept further.
Scantegrity is a security enhancement for optical scan voting systems. It's part of an emerging class of "end-to-end" independent election verification systems that permit each voter to verify that ...his or her ballot was correctly recorded and counted. On the Scantegrity ballot, each candidate position is paired with a random letter. Election officials confirm receipt of the ballot by posting the letter that is adjacent to the marked position. Scantegrity is the first voting system to offer strong independent verification without changing the way voters mark optical scan ballots, and it complies with legislative proposals requiring "unencrypted" paper audit records.
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