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The emergence of the concept of high-risk atherosclerotic plaque has led to considerable interest in noninvasive imaging techniques to identify high-risk features before clinical sequelae. For plaques in the carotid arteries, magnetic resonance imaging has undergone considerable histologic validation to link imaging features to indicators of plaque instability, including plaque burden, intraplaque hemorrhage, fibrous cap disruption, lipid rich necrotic core, and calcification. Recently introduced imaging technologies, especially those focused on three-dimensional imaging sequences, are now poised for integration into the clinical workup of patients with suspected carotid atherosclerosis. The purpose of this article is to review the carotid plaque magnetic resonance imaging techniques that are most ready for integration into the clinic.

Most studies examining rodent ultrasonic vocalizations (USVs) have investigated pericopulatory vocal behaviour in polygynous rodents, while vocalizations related to pair bond maintenance in monogamous rodents remain unexplored. In the monogamous California mouse, Peromyscus californicus, we used ultrasonic playbacks and post-playback social interactions to assess possible functions of USVs. We found that females responded with approach towards USVs of an unfamiliar male (bonded male from another pair) compared to a noise control, but displayed no difference in response to calls of their partner versus noise. Responsiveness to unfamiliar males does not appear to reflect an interest in extrapair copulations because during post-playback social interactions, females displayed more agonistic behaviours and fewer affiliative behaviours towards unfamiliar, sexually naive ‘stranger’ males than towards their partners. We speculate that approach to unfamiliar male USVs instead may be related to territorial defence. We further explored associations within the data set. Interestingly, female affiliation with her partner was predicted by USV output, particularly a higher number and proportion of complex call types, produced during the male partner USV elicitation phase. Female approach towards USVs was related to syllable duration of one call type in partner USVs (not in unfamiliar USVs) but no other features, and sufficient variation exists in syllable duration to allow females to theoretically distinguish between individuals based on this measure. Similarly, while pregnancy state did not influence female social behaviour, it decreased approach to playback of partner USVs but not to that of unfamiliar USVs. Overall, our results illuminate concepts about vocal communication in monogamous rodent species with strong pair bonds and suggest that functions of USVs in rodents can extend beyond mate choice.

Image processing plays a key role in vessel wall imaging. Vessel wall analysis typically requires multiple contrast-weighted imaging, image registration, and both qualitative and quantitative measurements to assess vessel wall status for disease. Image processing plays a key role in all these areas, and currently available software systems are capable of quantitative measurements of vessel area, thickness, eccentricity, and composition to assess vessel and disease status. New improvements in techniques and artificial intelligence offer new possibilities which can dramatically improve vessel wall analysis.

The management of security credentials (e.g., passwords, secret keys) for computational science workflows is a burden for scientists and information security officers. Problems with credentials (e.g., expiration, privilege mismatch) cause workflows to fail to fetch needed input data or store valuable scientific results, distracting scientists from their research by requiring them to diagnose the problems, re-run their computations, and wait longer for their results. SciTokens introduces a capabilities-based authorization infrastructure for distributed scientific computing, to help scientists manage their security credentials more reliably and securely. SciTokens uses IETF-standard OAuth JSON Web Tokens for capability-based secure access to remote scientific data. These access tokens convey the specific authorizations needed by the workflows, rather than general-purpose authentication impersonation credentials, to address the risks of scientific workflows running on distributed infrastructure including NSF resources (e.g., LIGO Data Grid, Open Science Grid, XSEDE) and public clouds (e.g., Amazon Web Services, Google Cloud, Microsoft Azure). By improving the interoperability and security of scientific workflows, SciTokens 1) enables use of distributed computing for scientific domains that require greater data protection and 2) enables use of more widely distributed computing resources by reducing the risk of credential abuse on remote systems. In this extended abstract, we present the results over the past year of our open source implementation of the SciTokens model and its deployment in the Open Science Grid, including new OAuth support added in the HTCondor 8.8 release series., 8 pages, 3 figures, PEARC '19: Practice and Experience in Advanced Research Computing, July 28-August 1, 2019, Chicago, IL, USA. arXiv admin note: substantial text overlap with arXiv:1807.04728

Over the past 15 years, proteasome inhibitors (PIs), namely bortezomib, carfilzomib (Cfz) and ixazomib, have significantly improved the overall survival and quality-of-life for multiple myeloma (MM) patients. However, a significant portion of MM patients do not respond to PI therapies. Drug resistance is present either de novo or acquired after prolonged therapy through mechanisms that remain poorly defined. The lack of a clear understanding of clinical PI resistance has hampered the development of next-generation PI drugs to treat MM patients who no longer respond to currently available therapies. Here, we designed and synthesized novel epoxyketone-based PIs by structural modifications at the P1′ site. We show that a Cfz analog, 9, harboring a hydroxyl substituent at its P1′ position was highly cytotoxic against cancer cell lines displaying de novo or acquired resistance to Cfz. These results suggest that peptide epoxyketones incorporating P1′-targeting moieties may have the potential to bypass resistance mechanisms associated with Cfz and to provide additional clinical options for patients resistant to Cfz.

Outside the HEP computing ecosystem, it is vanishingly rare to encounter user X509 certificate authentication (and proxy certificates are even more rare). The web never widely adopted the user certificate model, but increasingly sees the need for federated identity services and distributed authorization. For example, Dropbox, Google and Box instead use bearer tokens issued via the OAuth2 protocol to authorize actions on their services. Thus, the HEP ecosystem has the opportunity to reuse recent work in industry that now covers our needs. We present a token-based ecosystem for authorization tailored for use by CMS. We base the tokens on the SciTokens profile for the standardized JSON Web Token (JWT) format. The token embeds a signed description of what capabilities the VO grants the bearer; the site-level service can verify the VO’s signature without contacting a central service. In this paper, we describe the modifications done to enable token-based authorization in various software packages used by CMS, including XRootD, CVMFS, and HTCondor. We describe the token-issuing workflows that would be used to get tokens to running jobs in order to authorize data access and file stageout, and explain the advantages for hosted web services. Finally, we outline what the transition would look like for an experiment like CMS.

The management of security credentials (e.g., passwords, secret keys) for computational science workflows is a burden for scientists and information security officers. Problems with credentials (e.g., expiration, privilege mismatch) cause workflows to fail to fetch needed input data or store valuable scientific results, distracting scientists from their research by requiring them to diagnose the problems, re-run their computations, and wait longer for their results. In this paper, we introduce SciTokens, open source software to help scientists manage their security credentials more reliably and securely. We describe the SciTokens system architecture, design, and implementation addressing use cases from the Laser Interferometer Gravitational-Wave Observatory (LIGO) Scientific Collaboration and the Large Synoptic Survey Telescope (LSST) projects. We also present our integration with widely-used software that supports distributed scientific computing, including HTCondor, CVMFS, and XrootD. SciTokens uses IETF-standard OAuth tokens for capability-based secure access to remote scientific data. The access tokens convey the specific authorizations needed by the workflows, rather than general-purpose authentication impersonation credentials, to address the risks of scientific workflows running on distributed infrastructure including NSF resources (e.g., LIGO Data Grid, Open Science Grid, XSEDE) and public clouds (e.g., Amazon Web Services, Google Cloud, Microsoft Azure). By improving the interoperability and security of scientific workflows, SciTokens 1) enables use of distributed computing for scientific domains that require greater data protection and 2) enables use of more widely distributed computing resources by reducing the risk of credential abuse on remote systems., 8 pages, 6 figures, PEARC '18: Practice and Experience in Advanced Research Computing, July 22--26, 2018, Pittsburgh, PA, USA

Atherosclerosis imaging goes beyond the simple identification of luminal stenosis. Besides stenosis measurement, there are two main motivations for atherosclerosis imaging: one is to identify the so-called vulnerable plaque, defined as atherosclerotic plaque that poses increased risk of rupture and clinical events, such as heart attack or stroke; the other is to identify ‘positively remodelled’ plaques—plaques that grow outward from the lumen but cause minimal or no stenosis. Cardiovascular magnetic resonance (CMR) has histologically validated capabilities to characterize carotid plaque features in vivo, including a lipid-rich necrotic core, fibrous cap, intraplaque haemorrhage (IPH), calcification, and inflammation. A multicontrast two-dimensional imaging approach has been used in many prospective studies relating baseline CMR characteristics of carotid atherosclerosis with plaque progression and clinical events. These studies have demonstrated the importance of detecting IPH, lipid-rich necrotic cores, and fibrous caps. Building on these findings, a number of three-dimensional CMR techniques have been recently developed that allow higher spatial resolution plaque imaging and easier application clinically with short scan times. Three-dimensional plaque imaging offers flexible imaging plane and view angle analysis, large coverage, multivascular beds capability, and is a fast and cost-effective screening for clinical use. Atherosclerosis imaging has also been applied to detect plaques in other vascular beds such as the coronary artery, intracranial artery, and peripheral artery, although each bed comes with unique imaging needs. Large-scale studies are needed to determine the impact of atherosclerotic plaque CMR on patient outcomes.

When considering the idea of human settlement of outer space, the discussion evolves from research stations and small outposts to large-scale habitats and complex societies. The current international legal regime does not account for the development of civilizations and sovereignty in outer space and on celestial bodies. The reason for this lies in the principle of conflict prevention that pervades the Outer Space Treaty. This principle, righteous as it may be, does not fit the modern world scene. In fact, the very definition of outer space is centered around the Earth, archaically symbolizing a geocentric legal perspective of the universe. To allow for human settlement of outer space and celestial bodies, international law must address the concepts of civilizations and sovereignty. This can be done by redefining the human perspective of outer space according to the celestial subjectivity model, in which outer space becomes “the space outside of a celestial body’s gravity well relative to a state’s presence and perspective on that particular celestial body.” (Zach Miller, “On Celestial Subjectivity.” VAERO (2016). Available at https://www.vaeroresearch.com/single-post/2016/09/26/On-Celestial-Self-Determination.) The implications of altering the definition of outer space are both concrete and abstract, ranging from more clearly allowing national research stations to ensuring the right of self-determination within a future civilization of Mars colonists.

In order to ensure interoperability between middleware and authorization infrastructures used in the Open Science Grid (OSG) and the Enabling Grids for E-science (EGEE) projects, an Authorization Interoperability activity was initiated in 2006. The interoperability goal was met in two phases: firstly, agreeing on a common authorization query interface and protocol with an associated profile that ensures standardized use of attributes and obligations; and secondly implementing, testing, and deploying on OSG and EGEE, middleware that supports the interoperability protocol and profile. The activity has involved people from OSG, EGEE, the Globus Toolkit project, and the Condor project. This paper presents a summary of the agreed-upon protocol, profile and the software components involved.

MRI of carotid atherosclerosis provides a unique method to characterize plaque morphology and tissue composition, as well as, to a certain extent, plaque inflammation. Because of its noninvasiveness, it has many current and potential applications: the fact that it is the only technique that can examine the fibrous cap status in vivo makes it a powerful tool to identify high-risk plaques. With quantitative measurement achievable on a series of plaque compositional and morphologic features, this technique is also well suited for studying atherosclerosis progression and regression. This technique can also be combined with other imaging modalities such as ultrasound and nuclear medicine to create a comprehensive evaluation of carotid atherosclerosis from tissue compliance and composition to inflammation.

Previous studies have demonstrated that the tropism of Zika virus (ZIKV) for human neural stem cells (NSCs) leads to severe brain malformations. The proposed mechanisms underlying these brain malformations are thought to include the induction of apoptosis in neural progenitor/stem cells (Zhang et al., Nucleic Acid Res. 44:8610–8620, 2016). Previously, we observed many similarities between NSCs and brain tumor stem cells (BTSCs) (Wu et al., Stem Cells Dev., 17:173–184, 2008) and sought to determine if BTSC could support ZIKV replication. ZIKV infection of skin cells in vitro is mediated by the receptors AXL, DC-SIGN, TIM1, and TYRO3 (Hamel et al., J Virol. 89:8880–8896, 2015). We examined human embryonic brain tissue and have observed that the putative ZIKV receptor TIM1 is expressed by neuronal and astrocytic progenitor cells. Given the similarities between NSCs and BTSCs we examined human and rodent brain tumor cells for putative ZIKV receptor expression. We found TIM1 expression by human GBM6 glioma cells and murine GL261 gliomas. In tissue culture studies, incubation of ZIKV with human GBM6 cells led to high levels of infection. To determine the effects of ZIKV on tumor growth in vivo, we transplanted GL261 cells into the striatal area of the brain in syngeneic C57B/6 mice. Intra-tumoral injections of ZIKV were administered immediately after intra-cranial tumor implantation. Tumor-bearing mice receiving intra-tumoral injections of ZIKV exhibited prolonged survival in comparison to untreated mice. Together these results suggest that ZIKV may have potential as an oncolytic virus for targeting malignant brain tumors. (This work was supported in part by a grant from the Randy Shaver Cancer Research Foundation).

This study reports the incorporation of the antibiotics rifampin, doxycycline and clarithromycin in poly(styrene-co-methyl methacrylate films and their effect on biofilm prevention.Invasive procedures in patients such as surgical device, or intravenous or urinary catheter implantation, often results in complicated hospital-acquired nosocomial infections. Biofilm formation is essential to establish these infections on these devices and novel antibiotic delivery approaches are needed for more effective management.The films were evaluated in vitro for drug release and for their ability to prevent biofilm formation by methicillin susceptible and methicillin resistant Staphylococcus aureus. Surface tension components, obtained from contact angle measurements, and the morphology of the films evaluated by scanning electron microscopy were also investigated.In this study, antibiotic-loaded methacrylic copolymer films that effectively released rifampin, clarithromycin and doxycycline for up to 21 days prevented biofilm formation when tested in an in vitro bioreactor model. These drug loaded copolymer films provided the advantage by coating materials with a novel surface that was unsuitable for resettling of biofilms once the antibiotic was dissolved from the polymer surface. A combination of rifampin and clarithromycin released from the polymer film provided99.9% kill of an MRSA inoculate for up to 72 h.Results showed that combining multiple drugs in copolymer films with unique surface properties, initial hydrophilicity and increase in roughness, can be an effective way to prevent biofilm formation.

Many secure communication libraries used by distributed systems, such as SSL, TLS, and Kerberos, fail to make a clear distinction between the authentication, session, and communication layers. In this paper we introduce CEDAR, the secure communication library used by the Condor High Throughput Computing software, and present the advantages to a distributed computing system resulting from CEDAR's separation of these layers. Regardless of the authentication method used, CEDAR establishes a secure session key, which has the flexibility to be used for multiple capabilities. We demonstrate how a layered approach to security sessions can avoid round-trips and latency inherent in network authentication. The creation of a distinct session management layer allows for optimizations to improve scalability by way of delegating sessions to other components in the system. This session delegation creates a chain of trust that reduces the overhead of establishing secure connections and enables centralized enforcement of system-wide security policies. Additionally, secure channels based upon UDP datagrams are often overlooked by existing libraries; we show how CEDAR's structure accommodates this as well. As an example of the utility of this work, we show how the use of delegated security sessions and other techniques inherent in CEDAR's architecture enables US CMS to meet their scalability requirements in deploying Condor over large-scale, wide-area grid systems.

Despite recent advances in the understanding and etiology of cardiovascular disease, it remains the leading cause of morbidity and mortality worldwide. A great deal of research has been dedicated to investigating and identifying plaque instability: the so-called "vulnerable plaque". A reliable, in vivo, imaging method capable of identifying plaque characteristics associated with high-risk plaque will be immensely useful for evaluating plaque status and predicting future events. With excellent soft-tissue contrast and resolution, magnetic resonance imaging (MRI) has the ability to visualize features of vulnerable plaques, as well as perform longitudinal studies on the etiology, progression, and regression of atherosclerotic plaque. This review will cover the current state-of-the-art and new developments in carotid MRI to characterize atherosclerosis and its use in clinical diagnoses and longitudinal studies to understand mechanisms of lesion progression and regression.