A Type System for First-Class Layers with Inheritance, Subtyping, and Swapping

Context-Oriented Programming (COP) is a programming paradigm to encourage modularization of context-dependent software. Key features of COP are layers---modules to describe context-dependent behavioral variations of a software system---and their dynamic activation, which can modify the behavior of multiple objects that have already been instantiated. Typechecking programs written in a COP language is difficult because the activation of a layer can even change objects' interfaces. Inoue et al. have informally discussed how to make JCop, an extension of Java for COP by Appeltauer et al., type-safe. In this article, we formalize a small COP language called ContextFJ$_{<:}$ with its operational semantics and type system and show its type soundness. The language models main features of the type-safe version of JCop, including dynamically activated first-class layers, inheritance of layer definitions, layer subtyping, and layer swapping

ContextWorkflow: A Monadic DSL for Compensable and Interruptible Executions

Context-aware applications, whose behavior reactively depends on the time-varying status of the surrounding environment - such as network connection, battery level, and sensors - are getting more and more pervasive and important. The term "context-awareness" usually suggests prompt reactions to context changes: as the context change signals that the current execution cannot be continued, the application should immediately abort its execution, possibly does some clean-up tasks, and suspend until the context allows it to restart. Interruptions, or asynchronous exceptions, are useful to achieve context-awareness. It is, however, difficult to program with interruptions in a compositional way in most programming languages because their support is too primitive, relying on synchronous exception handling mechanism such as try-catch. We propose a new domain-specific language ContextWorkflow for interruptible programs as a solution to the problem. A basic unit of an interruptible program is a workflow, i.e., a sequence of atomic computations accompanied with compensation actions. The uniqueness of ContextWorkflow is that, during its execution, a workflow keeps watching the context between atomic actions and decides if the computation should be continued, aborted, or suspended. Our contribution of this paper is as follows; (1) the design of a workflow-like language with asynchronous interruption, checkpointing, sub-workflows and suspension; (2) a formal semantics of the core language; (3) a monadic interpreter corresponding to the semantics; and (4) its concrete implementation as an embedded domain-specific language in Scala

ContextWorkflow: A Monadic DSL for Compensable and Interruptible Executions (Artifact)

This artifact provides the Scala, Haskell, and Purescript implementations of ContextWorkflow, an embedded domain-specific language for interruptible and compensable executions, and demonstrates the maze search example described in the companion paper. The Haskell and Purescript implementations provide the core language constructs including texttt{checkpoint} for partial aborts and texttt{sub} for sub-workflows and show that ContextWorkflow can be embedded in eager and lazy languages as described in the companion paper. The Scala implementation does not only provide user-friendly syntax of ContextWorkflow but also gives the maze search example as an interactive GUI application

The effects of cavitation position on the velocity of a laser-induced microjet extracted using explainable artificial intelligence

The control of the velocity of a high-speed laser-induced microjet is crucial in applications such as needle-free injection. Previous studies have indicated that the jet velocity is heavily influenced by the volumes of secondary cavitation bubbles generated through laser absorption. However, there has been a lack of investigation of the relationship between the positions of cavitation bubbles and the jet velocity. In this study, we investigate the effects of cavitation bubbles on the jet velocity of laser-induced microjets extracted using explainable artificial intelligence (XAI). An XAI is used to classify the jet velocity from images of cavitation bubbles and to extract features from the images through visualization of the classification process. For this purpose, we run 1000 experiments and collect the corresponding images. The XAI model, which is a feedforward neural network (FNN), is trained to classify the jet velocity from the images of cavitation bubbles. After achieving a high classification accuracy, we analyze the classification process of the FNN. The predictions of the FNN, when considering the cavitation positions, show a higher correlation with the jet velocity than the results considering only cavitation volumes. Further investigation suggested that cavitation that occurs closer to the laser focus position has a higher acceleration effect. These results suggest that the velocity of a high-speed microjet is also affected by the cavitation position.Comment: 11 pages, 13 figures, 4 table

Temozolomide combined with irinotecan caused regression in an adult pleomorphic rhabdomyosarcoma patient-derived orthotopic xenograft (PDOX) nude-mouse model.

Adult pleomorphic rhabdomyosarcoma (RMS) is a rare and recalcitrant, highly-malignant mesenchymal tumor in need of improved therapeutic strategies. Our laboratory pioneered the patient-derived orthotopic xenograft (PDOX) nude mouse model with the technique of surgical orthotopic implantation (SOI). We previously described the development of a PDOX model of adult pleomorphic RMS where the tumor behaved similar to the patient donor. A high-grade pleomorphic rhabdomyosarcoma from a striated muscle was previously grown orthotopically in the right biceps-femoris muscle of nude mice to establish the PDOX model. In the present study, the PDOX models were randomized into the following treatment groups when tumor volume reached 100 mm3: G1, control without treatment; G2, cyclophosphamide (CPA) 140 mg/kg, intraperitoneal (i.p.) injection, weekly, for 3 weeks; G3, temozolomide (TEM), 25 mg/kg, per oral (p.o.), daily, for 21 days; G4, temozolomide (TEM) 25 mg/kg, p.o., daily, for 21 days combined with irinotecan (IRN), 4 mg/kg, i.p., daily for 21 days. After 3 weeks, treatment of PDOX with TEM combined with IRN was so powerful that it resulted in tumor regression and the smallest tumor volume compared to other groups. The RMS PDOX model should be of use to design the treatment program for the patient and for drug discovery and evaluation for this recalcitrant tumor type

Exquisite Tumor Targeting by Salmonella A1-R in Combination with Caffeine and Valproic Acid Regresses an Adult Pleomorphic Rhabdomyosarcoma Patient-Derived Orthotopic Xenograft Mouse Model.

Adult pleomorphic rhabdomyosarcoma (RMS) is a rare and malignant mesenchymal tumor. Recently, we developed a patient-derived orthotopic xenograft (PDOX) model of adult pleomorphic RMS. In the present study, we evaluated the efficacy of tumor-targeting Salmonella typhimurium (S. typhimurium) A1-R combined with caffeine (CAF) and valproic acid (VPA) on the adult RMS PDOX. An adult pleomorphic RMS cell line was established from the PDOX model. Cell survival after exposure to CAF and VPA was assessed, and the IC50 value was calculated for each drug. The RMS PDOX models were randomized into five groups: untreated control; tumor treated with cyclophosphamide (CPA); tumor treated with CAF + VPA; tumor treated with S. typhimurium A1-R; and tumor treated with S. typhimurium A1-R + CAF + VPA. Tumor size and body weight was measured twice a week. VPA caused a concentration-dependent cytocidal effect. A synergistic effect of combination treatment with CAF was observed against the RMS cell line. For the in vivo study, all treatments significantly inhibited tumor growth compared with the untreated control. S. typhimurium A1-R combined with VPA and CAF was significantly more effective than CPA, VPA combined with CAF, or S. typhimurium A1-R alone and significantly regressed the tumor volume compared with day 0. These results suggest that S. typhimurium A1-R together with VPA and CAF could regresses an adult pleomorphic RMS in a PDOX model and therefore has important future clinical potential

Recombinant methioninase combined with doxorubicin (DOX) regresses a DOX-resistant synovial sarcoma in a patient-derived orthotopic xenograft (PDOX) mouse model.

Synovial sarcoma (SS) is a recalcitrant subgroup of soft tissue sarcoma (STS). A tumor from a patient with high grade SS from a lower extremity was grown orthotopically in the right biceps femoris muscle of nude mice to establish a patient-derived orthotopic xenograft (PDOX) mouse model. The PDOX mice were randomized into the following groups when tumor volume reached approximately 100 mm3: G1, control without treatment; G2, doxorubicin (DOX) (3 mg/kg, intraperitoneal [i.p.] injection, weekly, for 2 weeks; G3, rMETase (100 unit/mouse, i.p., daily, for 2 weeks); G4 DOX (3mg/kg), i.p. weekly, for 2 weeks) combined with rMETase (100 unit/mouse, i.p., daily, for 2 weeks). On day 14 after treatment initiation, all therapies significantly inhibited tumor growth compared to untreated control, except DOX: (DOX: p = 0.48; rMETase: p &lt; 0.005; DOX combined with rMETase &lt; 0.0001). DOX combined with rMETase was significantly more effective than both DOX alone (p &lt; 0.001) and rMETase alone (p &lt; 0.05). The relative body weight on day 14 compared with day 0 did not significantly differ between any treatment group or untreated control. The results indicate that r-METase can overcome DOX-resistance in this recalcitrant disease

Temozolomide combined with irinotecan regresses a cisplatinum-resistant relapsed osteosarcoma in a patient-derived orthotopic xenograft (PDOX) precision-oncology mouse model.

Relapsed osteosarcoma is a recalcitrant tumor. A patient's cisplatinum (CDDP)-resistant relapsed osteosarcoma lung metastasis was previously established orthotopically in the distal femur of mice to establish a patient-derived orthotopic xenograft (PDOX) model. In the present study, the PDOX models were randomized into the following groups when tumor volume reached 100 mm3: G1, control without treatment; G2, CDDP (6 mg/kg, intraperitoneal (i.p.) injection, weekly, for 2 weeks); gemcitabine (GEM) (100 mg/kg, i.p., weekly, for 2 weeks) combined with docetaxel (DOC) (20 mg/kg, i.p., once); temozolomide (TEM) (25 mg/kg, p.o., daily, for 2 weeks) combined with irinotecan (IRN) (4 mg/kg i.p., daily for 2 weeks). Tumor size and body weight were measured with calipers and a digital balance twice a week. After 2 weeks, all treatments significantly inhibited tumor growth except CDDP compared to the untreated control: CDDP: p = 0.093; GEM+DOC: p = 0.0002, TEM+IRN: p &lt; 0.0001. TEM combined with IRN was significantly more effective than either CDDP (p = 0.0001) or GEM combined with DOC (p = 0.0003) and significantly regressed the tumor volume compared to day 0 (p = 0.003). Thus the PDOX model precisely identified the combination of TEM-IRN that could regress the CDDP-resistant relapsed metastatic osteosarcoma PDOX

Using spin to understand the formation of LIGO's black holes

With the detection of four candidate binary black hole (BBH) mergers by the Advanced LIGO detectors thus far, it is becoming possible to constrain the properties of the BBH merger population in order to better understand the formation of these systems. Black hole (BH) spin orientations are one of the cleanest discriminators of formation history, with BHs in dynamically formed binaries in dense stellar environments expected to have spins distributed isotropically, in contrast to isolated populations where stellar evolution is expected to induce BH spins preferentially aligned with the orbital angular momentum. In this work we propose a simple, model-agnostic approach to characterizing the spin properties of LIGO's BBH population. Using measurements of the effective spin of the binaries, which is LIGO's best constrained spin parameter, we introduce a simple parameter to quantify the fraction of the population that is isotropically distributed, regardless of the spin magnitude distribution of the population. Once the orientation characteristics of the population have been determined, we show how measurements of effective spin can be used to directly constrain the underlying BH spin magnitude distribution. Although we find that the majority of the current effective spin measurements are too small to be informative, with LIGO's four BBH candidates we find a slight preference for an underlying population with aligned spins over one with isotropic spins (with an odds ratio of 1.1). We argue that it will be possible to distinguish symmetric and anti-symmetric populations at high confidence with tens of additional detections, although mixed populations may take significantly more detections to disentangle. We also derive preliminary spin magnitude distributions for LIGO's black holes, under the assumption of aligned or isotropic populations