Huy Tran

Small-molecule nociceptin receptor agonist ameliorates mast cell activation and pain in sickle mice.

Treatment of pain with morphine and its congeners in sickle cell anemia is suboptimal, warranting the need for analgesics devoid of side effects, addiction and tolerance liability. Small-molecule nociceptin opioid receptor ligands show analgesic efficacy in acute and chronic pain models. We show that AT-200, a high affinity nociceptin opioid receptor agonist with low efficacy at the mu opioid receptor, ameliorated chronic and hypoxia/reoxygenation-induced mechanical, thermal and deep tissue/musculoskeletal hyperalgesia in HbSS-BERK sickle mice. The antinociceptive effect of AT-200 was antagonized by SB-612111, a nociceptin opioid receptor antagonist, but not naloxone, a non-selective mu opioid receptor antagonist. Daily 7-day treatment with AT-200 did not develop tolerance and showed a sustained anti-nociceptive effect, which improved over time and led to reduced plasma serum amyloid protein, neuropeptides, inflammatory cytokines and mast cell activation in the periphery. These data suggest that AT-200 ameliorates pain in sickle mice via the nociceptin opioid receptor by reducing inflammation and mast cell activation without causing tolerance. Thus, nociceptin opioid receptor agonists are promising drugs for treating pain in sickle cell anemia.

On the mixing time of directed social graphs and security implications

Many graphs in general, and social graphs in particular, are directed by nature. However, applications built on top of social networks, including Sybil defenses, information routing and dissemination, and anonymous communication require mutual relationships which produce undirected graphs. When undirected graphs are used as testing tools for these applications to bring insight on their usability and potential deployment, directed graphs are converted into undirected graphs by omitting edge directions or by augmenting graphs. Unfortunately, it is unclear how altering these graphs affects the quality of their mixing time. Motivated by the lack of prior work on this problem, we investigate mathematical tools for measuring the mixing time of directed social graphs and its associated error bounds. We use these tools to measure the mixing time of several benchmarking directed graphs and their undirected counterparts. We then measure how this difference impacts two applications built on top of social networks: a Sybil defense mechanism and an anonymous communication system.

Trustworthy distributed computing on social networks

In this paper we investigate a new computing paradigm, called SocialCloud, in which computing nodes are governed by social ties driven from a bootstrapping trust-possessing social graph. We investigate how this paradigm differs from existing computing paradigms, such as grid computing and the conventional cloud computing paradigms. We show that incentives to adopt this paradigm are intuitive and natural, and security and trust guarantees provided by it are solid. We propose metrics for measuring the utility and advantage of this computing paradigm, and using real-world social graphs and structures of social traces; we investigate the potential of this paradigm for ordinary users. We study several design options and trade-offs, such as scheduling algorithms, centralization, and straggler handling, and show how they affect the utility of the paradigm. Interestingly, we conclude that whereas graphs known in the literature for high trust properties do not serve distributed trusted computing algorithms, such as Sybil defenses-for their weak algorithmic properties, such graphs are good candidates for our paradigm for their self-load-balancing features.

Comparative Analysis of Pain Behaviours in Humanized Mouse Models of Sickle Cell Anemia.

Pain is a hallmark feature of sickle cell anemia (SCA) but management of chronic as well as acute pain remains a major challenge. Mouse models of SCA are essential to examine the mechanisms of pain and develop novel therapeutics. To facilitate this effort, we compared humanized homozygous BERK and Townes sickle mice for the effect of gender and age on pain behaviors. Similar to previously characterized BERK sickle mice, Townes sickle mice show more mechanical, thermal, and deep tissue hyperalgesia with increasing age. Female Townes sickle mice demonstrate more hyperalgesia compared to males similar to that reported for BERK mice and patients with SCA. Mechanical, thermal and deep tissue hyperalgesia increased further after hypoxia/reoxygenation (H/R) treatment in Townes sickle mice. Together, these data show BERK sickle mice exhibit a significantly greater degree of hyperalgesia for all behavioral measures as compared to gender- and age-matched Townes sickle mice. However, the genetically distinct “knock-in” strategy of human α and β transgene insertion in Townes mice as compared to BERK mice, may provide relative advantage for further genetic manipulations to examine specific mechanisms of pain.

Understanding Social Networks Properties for Trustworthy Computing

The ever-increasing popularity of social networks opens new directions for leveraging social networks to build primitives for security and communication, in many contexts. Such primitives utilize the trust in these social networks to ensure collaboration and algorithmic properties exhibited in such networks to argue for the effectiveness of such primitives. Despite the importance of such properties and their quality to the operation of these primitives, less effort is made to measure these properties and understand the relationship among them and to other characteristics of social networks. We extend our earlier results measuring the mixing time, to investigate a new property used for building Sybil defenses, namely the expansion of social graphs. We measure the expansion of social graphs, and show quantitatively that, with a few exceptions, it is sufficient to support Sybil defense mechanisms based on expansion. We relate the mixing time of social graphs to graph degeneracy, which captures cohesiveness of the graph. We experimentally show that fast-mixing graphs tend to have a larger single core whereas slow mixing graphs tend to have smaller multiple cores. While this study provides quantitative evidence relating the mixing time to coreness of the graph, it also agrees with our previous observations about the tight-knit community structure in slow mixing social graphs.

Trustworthy Distributed Computing on Social Networks

In this paper we investigate a new computing paradigm, called SocialCloud, in which computing nodes are governed by social ties driven from a bootstrapping trust-possessing social graph. We investigate how this paradigm differs from existing computing paradigms, such as grid computing and the conventional cloud computing paradigms. We show that incentives to adopt this paradigm are intuitive and natural, and security and trust guarantees provided by it are solid. We propose metrics for measuring the utility and advantage of this computing paradigm, and using real-world social graphs and structures of social traces; we investigate the potential of this paradigm for ordinary users. We study several design options and trade-offs, such as scheduling algorithms, centralization, and straggler handling, and show how they affect the utility of the paradigm. Interestingly, we conclude that whereas graphs known in the literature for high trust properties do not serve distributed trusted computing algorithms, such as Sybil defenses--for their weak algorithmic properties, such graphs are good candidates for our paradigm for their self-load-balancing features.

HCV Induces Telomerase Reverse Transcriptase, Increases Its Catalytic Activity, and Promotes Caspase Degradation in Infected Human Hepatocytes.

Introduction Telomerase repairs the telomeric ends of chromosomes and is active in nearly all malignant cells. Hepatitis C virus (HCV) is known to be oncogenic and potential interactions with the telomerase system require further study. We determined the effects of HCV infection on human telomerase reverse transcriptase (TERT) expression and enzyme activity in primary human hepatocytes and continuous cell lines. Results Primary human hepatocytes and Huh-7.5 hepatoma cells showed early de novo TERT protein expression 2–4 days after infection and these events coincided with increased TERT promoter activation, TERT mRNA, and telomerase activity. Immunoprecipitation studies demonstrated that NS3-4A protease-helicase, in contrast to core or NS5A, specifically bound to the C-terminal region of TERT through interactions between helicase domain 2 and protease sequences. Increased telomerase activity was noted when NS3-4A was transfected into cells, when added to reconstituted mixtures of TERT and telomerase RNA, and when incubated with high molecular weight telomerase ‘holoenzyme’ complexes. The NS3-4A catalytic effect on telomerase was inhibited with primuline or danoprevir, agents that are known to inhibit NS3 helicase and protease activities respectively. In HCV infected cells, NS3-4A could be specifically recovered with telomerase holoenzyme complexes in contrast to NS5A or core protein. HCV infection also activated the effector caspase 7 which is known to target TERT. Activation coincided with the appearance of lower molecular weight carboxy-terminal fragment(s) of TERT, chiefly sized at 45 kD, which could be inhibited with pancaspase or caspase 7 inhibitors. Conclusions HCV infection induces TERT expression and stimulates telomerase activity in addition to triggering Caspase activity that leads to increased TERT degradation. These activities suggest multiple points whereby the virus can influence neoplasia. The NS3-4A protease-helicase can directly bind to TERT, increase telomerase activity, and thus potentially influence telomere repair and host cell neoplastic behavior.

Prostatitis, Steatitis, and Diarrhea in a Dog following Presumptive Flea-Borne Transmission of Bartonella henselae

ABSTRACT Bartonella henselae is increasingly associated with a variety of pathological entities, which are often similar in dogs and human patients. Following an acute flea infestation, a dog developed an unusual clinical presentation for canine bartonellosis. Comprehensive medical, microbiological, and surgical interventions were required for diagnosis and to achieve a full recovery.