Non Interference for Intuitionist Necessity

The necessity modality of intuitionist S4 is a comonad. In this paper, we study indexed necessity modalities that provide the logical foundation for a variety of applications; for example, to model possession of capabilities in policy languages for access control, and to track exceptions in type theories for exceptional computation. Noninterference properties of the intuitionist logic of indexed necessity modalities capture the limitations on the information flow between formulas that are under the scope of necessity modalities with different indices. The impact of noninterference is seen in the unprovability of certain formulas. Noninterference is necessary for several applications. In models of capabilities, noninterference facilitates distributed reasoning. In models of exceptions, noninterference is necessary to ensure that the exceptions are tracked conservatively. In this paper, we prove noninterference properties for indexed intuitionist necessity S4 modalities. To our knowledge, this is the first examination of noninterference results for the intuitionist S4 necessity modality (even without indexing)

Lambda-RBAC: Programming with Role-Based Access Control

We study mechanisms that permit program components to express role constraints on clients, focusing on programmatic security mechanisms, which permit access controls to be expressed, in situ, as part of the code realizing basic functionality. In this setting, two questions immediately arise: (1) The user of a component faces the issue of safety: is a particular role sufficient to use the component? (2) The component designer faces the dual issue of protection: is a particular role demanded in all execution paths of the component? We provide a formal calculus and static analysis to answer both questions.Comment: LMC

Succour to the Confused Deputy Types for Capabilities

Abstract. The possession of secrets is a recurrent theme in security literature and practice. We present a refinement type system, based on indexed intuitonist S4 necessity, for an object calculus with explicit locations (corresponding to principals) to control the principals that may possess a secret. Type safety ensures that if the execution of a well-typed program leads to a configuration with an object p located at principal a, then a possesses the capability to p. We illustrate the type system with simple examples drawn from web applications, including an illustration of how Cross-Site Request Forgery (CSRF) vulnerabilities may manifest themselves as absurd refinements on object declarations during type checking. This is an extended version of a paper that appears in APLAS 2012

Bostonia: v. 64, no. 1

Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs

Characterization and management of adverse events observed with mobocertinib (TAK-788) treatment for EGFR exon 20 insertion–positive non–small cell lung cancer

Carcinoma; Càncer de pulmó de cèl·lules no petites; Seguretat del pacientCarcinoma; Cáncer de pulmón de células no pequeñas; Seguridad del pacienteCarcinoma; Non–small cell lung cancer; Patient safetyBackground Mobocertinib has demonstrated durable clinical benefit in platinum-pretreated patients (PPP) with epidermal growth factor receptor exon 20 insertion–positive non–small cell lung cancer (NSCLC). Research design and methods Pooled safety analysis of two studies included patients with NSCLC (N = 257) treated with the recommended phase 2 dose (RP2D) of mobocertinib (160 mg once daily). We report overall safety (treatment-emergent adverse events [TEAEs]) in the RP2D population; characterization of GI and skin-related events in 114 PPP from a phase 1/2 study (NCT02716116); and clinical activity in PPP with and without dose reductions due to TEAEs. Results In the RP2D population (N = 257), the most common TEAEs were diarrhea (93%), nausea (47%), rash (38%), and vomiting (37%). In PPP (N = 114), median times to diarrhea onset and resolution were 5 and 2 days, respectively. Median times to onset and resolution of skin-related events were 9 and 78 days, respectively. Among PPP with (n = 29) or without (n = 85) dose reductions due to TEAEs, overall response rates were 21% and 31% and median durations of response were 5.7 and 17.5 months, respectively. Conclusions GI and skin-related events are common with mobocertinib; minimizing dose reductions with proactive management may improve clinical outcomes.The paper received funding from Takeda Development Center Americas Inc., Lexington, MA, USA

Acquired Resistance to KRAS (G12C) Inhibition in Cancer

BACKGROUND: Clinical trials of the KRAS inhibitors adagrasib and sotorasib have shown promising activity in cancers harboring KRAS glycine-to-cysteine amino acid substitutions at codon 12 (KRAS(G12C)). The mechanisms of acquired resistance to these therapies are currently unknown. METHODS: Among patients with KRAS(G12C) -mutant cancers treated with adagrasib monotherapy, we performed genomic and histologic analyses that compared pretreatment samples with those obtained after the development of resistance. Cell-based experiments were conducted to study mutations that confer resistance to KRAS(G12C) inhibitors. RESULTS: A total of 38 patients were included in this study: 27 with non-small-cell lung cancer, 10 with colorectal cancer, and 1 with appendiceal cancer. Putative mechanisms of resistance to adagrasib were detected in 17 patients (45% of the cohort), of whom 7 (18% of the cohort) had multiple coincident mechanisms. Acquired KRAS alterations included G12D/R/V/W, G13D, Q61H, R68S, H95D/Q/R, Y96C, and high-level amplification of the KRAS(G12C) allele. Acquired bypass mechanisms of resistance included MET amplification; activating mutations in NRAS, BRAF, MAP2K1, and RET; oncogenic fusions involving ALK, RET, BRAF, RAF1, and FGFR3; and loss-of-function mutations in NF1 and PTEN. In two of nine patients with lung adenocarcinoma for whom paired tissue-biopsy samples were available, histologic transformation to squamous-cell carcinoma was observed without identification of any other resistance mechanisms. Using an in vitro deep mutational scanning screen, we systematically defined the landscape of KRAS mutations that confer resistance to KRAS(G12C) inhibitors. CONCLUSIONS: Diverse genomic and histologic mechanisms impart resistance to covalent KRAS(G12C) inhibitors, and new therapeutic strategies are required to delay and overcome this drug resistance in patients with cancer. (Funded by Mirati Therapeutics and others; ClinicalTrials.gov number, NCT03785249.)

Type-Safe Execution of Mobile Agents in Anonymous Networks

. We present a partially-typed semantics for Dp, a distributed p-calculus. The semantics is designed for open distributed systems in which some sites may harbor malicious agents. Nonetheless, the semantics guarantee traditional type-safety properties at "good" locations by using a mixture of static and dynamic type-checking. The run-time semantics is built on the model of an anonymous network where the source of incoming agents is unknowable. To counteract possible misuse of resources all sites keep a record of local resources against which incoming agents are dynamically typechecked. 1 Introduction In [7] we presented a type system for controlling the use of resources in a distributed system. The type system guarantees that resource access is always safe, in the sense that, for example, integer channels are always used with integers and boolean channels are always used with booleans. The type system of [7], however, requires that all agents in the system be well-typed. In open syste..