Phase 1b/2a trial of the superoxide dismutase mimetic GC4419 to reduce chemoradiotherapy-induced oral mucositis in patients with oral cavity or oropharyngeal carcinoma

PURPOSE: To assess the safety of the superoxide dismutase mimetic GC4419 in combination with radiation and concurrent cisplatin for patients with oral cavity or oropharyngeal cancer (OCC) and to assess the potential of GC4419 to reduce severe oral mucositis (OM). PATIENTS AND METHODS: Patients with locally advanced OCC treated with definitive or postoperative intensity modulated radiation therapy (IMRT) plus cisplatin received GC4419 by 60-minute intravenous infusion, ending \u3c60 minutes before IMRT, Monday through Friday for 3 to 7 weeks, in a dose and duration escalation study. Oral mucositis was assessed twice weekly during and weekly after IMRT. RESULTS: A total of 46 patients received GC4419 in 11 separate dosing and duration cohorts: dose escalation occurred in 5 cohorts receiving 15 to 112 mg/d over 3 weeks (n=20), duration escalation in 3 cohorts receiving 112 mg/d over 4 to 6 weeks (n=12), and then 3 additional cohorts receiving 30 or 90 mg/d over 6 to 7 weeks (n=14). A maximum tolerated dose was not reached. One dose-limiting toxicity (grade 3 gastroenteritis and vomiting with hyponatremia) occurred in each of 2 separate cohorts at 112 mg. Nausea/vomiting and facial paresthesia during infusion seemed to be GC4419 dose-related. Severe OM occurred through 60 Gy in 4 of 14 patients (29%) dosed for 6 to 7 weeks, with median duration of only 2.5 days. CONCLUSIONS: The safety of GC4419 concurrently with chemoradiation for OCC was acceptable. Toxicities included nausea/vomiting and paresthesia. Doses of 30 and 90 mg/d administered for 7 weeks were selected for further study. In an exploratory analysis, severe OM seemed less frequent and briefer than expected

A Promiscuous DNA Packaging Machine from Bacteriophage T4

Packaged viral genome can be removed from bacteriophage T4 capsid and the capsid refilled with any double-stranded DNA, single or multiple molecules, using a powerful ATP-fueled DNA packaging machine

A Domain Specific Design Tool for Spacecraft System Behavior

Specification of spacecraft subsystem interactions is typically carried out using informal diagrams and descriptions that can obscure subtle ambiguities and inconsistencies. As a result, problems in the way subsystems are designed to interact may remain undetected until the integration and test phase, when the cost of change is high. Our Behavioral Analysis of Spacecraft Systems (BASS) modeling tool provides a structured way to define spacecraft subsystem interfaces and interactions, and access to an underlying formal model of interaction that allows the specified interactions to be rigorously analyzed. The enforced consistency of the diagrams produced by our tool and the analytical power of the underlying formal model increases a developer’s ability to discover and correct system design errors early in the development process

Strongly-transferring memorized examples in deep neural networks

This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Thesis: M. Eng. in Computer Science and Engineering, Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2019Cataloged from student-submitted PDF version of thesis.Includes bibliographical references (pages 59-60).Training deep neural networks requires large quantities of labeled training data, on the order of thousands of examples per class. These requirements make model training both time-consuming and expensive, which provides an incentive for adversaries to steal, or copy, other users' models. In this work, we examine a recent defense method called neural network watermarking via memorized examples, where an owner intentionally trains his model to mislabel particular inputs. We try to isolate the mechanism by which memorized examples are learned by a model in order to better evaluate their robustness. We find that memorized examples are indeed strongly embedded in trained models and actually transfer to stolen models under one form of model stealing. When access to local input-logit gradient information is used by an attacker, the stolen model also learns to mislabel the memorized examples. We show that this transfer is robust to architecture mismatch and perturbations of the query set used for stealing. We present different possible mechanisms for memorized example transfer and find that local input geometry is insufficient to explain the phenomenon. Finally, we describe a simple method for a model owner to boost the transfer rate of memorized examples, increasing their effectiveness as a defense against model stealing.by Abhinav S. Venigalla.M. Eng. in Computer Science and EngineeringM.Eng.inComputerScienceandEngineering Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Scienc

PointerViz - Towards Visualizing Pointers for Novice Programmers

Pointers are considered as one of the key concepts in learning programming and are extensively used for implementing several data structures. They lay the foundation for handling dynamic aspects of a program, increase execution speed and handle data types with more efficiency. This makes it critical for budding programmers to be well versed with using pointers. However, most of the novice programmers find it difficult and tricky to understand concepts such as address allocations, pointers referring pointers and data structures containing pointers. Hence, drawing the physical structure and flow of pointers is considered to be a common learning practice to gain better clarity and avoid confusion when learning pointers. But, it is time consuming and tedious to draw the flow of pointers on paper while programming. To help programmers understand these variations in pointers, we propose PointerViz as a Google Chrome extension that displays the pictorial representation of selected code with pointers. We conducted a preliminary survey with 40 students from various universities and 83% of the users reported positive experience with the plugin

Allelic drop-out may occur with a primer binding site polymorphism for the commonly used RFLP assay for the -1131T>C polymorphism of the Apolipoprotein AV gene.

Apolipoprotein AV (ApoAV) gene variant, -1131T>C, is associated with increased triglyceride concentrations in all ethnic groups studied. An MseI based RFLP analysis is the most commonly used method for genotyping this SNP. We genotyped a large cohort comprising 1185 Asian Indians and 173 UK Caucasians for -1131T>C using an ARMS-PCR based tetra-primer method. For quality control, we re-genotyped approximately 10% random samples from this cohort utilizing the MseI RFLP, which showed a 2.9% (3/102) genotyping error rate between the two methods. To investigate further, we sequenced the 900 bp region around the -1131T>C polymorphism in 25 Asian Indians and 15 UK Caucasians and found a number of polymorphisms including the -987C>T polymorphism. Further analysis of the -987C>T SNP showed a higher rare allele frequency of 0.23 in Asian Indians (n = 158) compared to 0.09 in the UK Caucasians (n = 157). This SNP is located 4 bp from the 3' end of the RFLP forward primer and is in weak linkage disequilibrium with -1131T>C variant (r2 = 0.084 and D' = 1). Repeated RFLP analysis of seven subjects heterozygous for -987C>T (seven times), showed discordant results with the sequence at -1131T>C SNP nearly one third (15/49) of the time. We conclude that presence of -987C>T polymorphism in the forward primer of the MseI RFLP assay may lead to allelic drop-out and generate unforeseen errors in genotyping the -1131T>C polymorphism. Our results also emphasise the need for careful quality control in all molecular genetic studies, particularly while transferring genotyping methods between various ethnic groups

Fluctuations in productivity and denitrification in the southeastern Arabian Sea during the late Quaternary

Sedimentological and stable isotopic characteristics of sediments have been studied in a core from the southeastern Arabian Sea containing records of the past 70 ka. Palaeoproductivity proxies such as organic carbon (Corg), total nitrogen (TN) and calcium carbonate (CaCO3) contents, show high values at the core top and during the Last Glacial Maximum (LGM) and marine isotope stage (MIS) 4, suggesting high productivity, whereas low Corg and CaCO3 contents are associated with the MIS 1/2 and mid-MIS 3, indicating reduced productivity. The δ18O values in planktonic foraminifera range between - 2.7‰ and - 0.1‰, with a large glacial-interglacial amplitude Δδ18O of ~ 2.6‰, suggesting changes related to monsoonal precipitation/runoff. The δ15N values fluctuate between 5.4‰ and 7.3‰, signifying variation in denitrification intensity. The δ15N indicates an overall increase in denitrification intensity during MIS 1 and MIS 3 and, reduced intensity during MIS 1/2, LGM and mid-MISHigher primary productivity and reduced denitrification intensity during LGM and MIS 4 might be due to convective winter mixing and more oxygenated subsurface waters. Reduced primary productivity during MIS 1/2 and mid-MIS 3 might be the effect of enhanced precipitation associated with the intensified southwest monsoon fortifying near-surface stratification