In vitro reconstitution of TDP-2-deoxynogalamine

Nogalamycin is an anthracycline compound produced by Streptomyces nogalater. Anthracyclines have been shown to be highly effective against cancer tissues, and anthracyclines such as daunorubicin are at the center of many chemotherapy treatments. However, anthracyclines are also highly toxic, particularly to the heart, making it necessary for the continuing study of this group of compounds. Similar to other anthracyclines, nogalamycin also shows antitumor activity. However, also similar to many other anthracyclines, its cardiotoxicity precludes its use as a clinical drug. In the past, semisynthesis has been successful in producing anthracycline analogs that have greater efficacy and lower cardiotoxicity. However, the success rate has been very low, with only a handful of potential candidates out of thousands of new compounds ever making it to clinical trials. Therefore, a more efficient way of generating new anthracyclines is needed to find better chemotherapy drugs. Towards this end, we have expressed and purified several proteins in the nogalamycin biosynthesis gene cluster in order to better understand how nature produces these products and harness that knowledge for future bioengineering efforts. Specifically, we have focused on the enzymes involved in modification and synthesis of nogalamine, the amino sugar essential for nogalamycin activity, and assayed the activities of SnogF, SnogG, SnogA, and SnogX.Biochemistr

The Use of Bug Bounty Programs for Software Reliability Improvement

As the number of security breaches caused by third-party applications significantly increased, digital platforms are launching BBPs to help improve software reliability. BBPs bring benefits to the platform and vendors, meanwhile impose additional costs; and may change the vendors’ reliability investment incentive. We build a model to examine strategic decisions of launching and participating in a BBP for the platform and third-party vendor, respectively. We find that the platform’s (vendor’s) launching (participation) decisions depend on two key factors: the expected loss due to security breaches and the vendor’s investment efficiency. The incentive of using BBP, for the platform and vendor, sometimes is inconsistent. Only when the potential loss is high and investment efficiency is low, BBP would be the equilibrium outcome. We find using the BBP is not always socially optimal. Under certain conditions, it reduces the overall software reliability, makes the platform less reliable, and hurts end users

An Economic Analysis of Third-Party Software Reliability Improvement using the Bug Bounty Program

Bug Bounty Programs (BBPs) reward external hackers for reporting software vulnerabilities. As the number of security issues caused by third-party applications has been significantly increased recently, many digital platforms are considering launching BBPs to help improve the reliability of third-party software. In this paper, we present an analytical model to examine the strategic decisions of launching and participating in a BBP for the platform and the third-party vendor, respectively. We find that the platform’s (the vendor’s) BBP launching (participation) decisions depend on two key factors: the expected loss due to security breaches and the vendor’s reliability investment efficiency. We show that the incentive of using BBP, for the platform and vendor, sometimes is inconsistent. Meanwhile, we find that using the BBP is not always socially optimal. Under certain conditions, it reduces the overall software reliability, instead of improving it, makes the platform marketplace less secure, and thus hurts end users

Non-standard neutrino interactions in IceCube

Non-standard neutrino interactions (NSI) may arise in various types of new physics. Their existence would change the potential that atmospheric neutrinos encounter when traversing Earth matter and hence alter their oscillation behavior. This imprint on coherent neutrino forward scattering can be probed using high-statistics neutrino experiments such as IceCube and its low-energy extension, DeepCore. Both provide extensive data samples that include all neutrino flavors, with oscillation baselines between tens of kilometers and the diameter of the Earth. DeepCore event energies reach from a few GeV up to the order of 100 GeV - which marks the lower threshold for higher energy IceCube atmospheric samples, ranging up to 10 TeV. In DeepCore data, the large sample size and energy range allow us to consider not only flavor-violating and flavor-nonuniversal NSI in the μ−τ sector, but also those involving electron flavor. The effective parameterization used in our analyses is independent of the underlying model and the new physics mass scale. In this way, competitive limits on several NSI parameters have been set in the past. The 8 years of data available now result in significantly improved sensitivities. This improvement stems not only from the increase in statistics but also from substantial improvement in the treatment of systematic uncertainties, background rejection and event reconstruction

IceCube Search for Earth-traversing ultra-high energy Neutrinos

The search for ultra-high energy neutrinos is more than half a century old. While the hunt for these neutrinos has led to major leaps in neutrino physics, including the detection of astrophysical neutrinos, neutrinos at the EeV energy scale remain undetected. Proposed strategies for the future have mostly been focused on direct detection of the first neutrino interaction, or the decay shower of the resulting charged particle. Here we present an analysis that uses, for the first time, an indirect detection strategy for EeV neutrinos. We focus on tau neutrinos that have traversed Earth, and show that they reach the IceCube detector, unabsorbed, at energies greater than 100 TeV for most trajectories. This opens up the search for ultra-high energy neutrinos to the entire sky. We use ten years of IceCube data to perform an analysis that looks for secondary neutrinos in the northern sky, and highlight the promise such a strategy can have in the next generation of experiments when combined with direct detection techniques

Posteriori analysis on IceCube double pulse tau neutrino candidates

The IceCube Neutrino Observatory at the South Pole detects Cherenkov light emitted by charged secondary particles created by primary neutrino interactions. Double pulse waveforms can arise from charged current interactions of astrophysical tau neutrinos with nucleons in the ice and the subsequent decay of tau leptons. The previous 8-year tau double pulse analysis found three tau neutrino candidate events. Among them, the most promising one observed in 2014 is located very near the dust layer in the middle of the detector. A posterior analysis on this event will be presented in this paper, using a new ice model treatment with continuously varying nuisance parameters to do the targeted Monte Carlo re-simulation for tau and other background neutrino ensembles. The impact of different ice models on the expected signal and background statistics will also be discussed