bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hardware Trojan Detection Using the Order of Path Delay
Authors: Cui Xiaotong , Koopahi Elnaz , Wu Kaijie , Karri Ramesh 
Published: October 2018

Many fabrication-less design houses are outsourcing their designs to third-party foundries for fabrication to lower cost. This IC development process, however, raises serious security concerns on Hardware Trojans (HTs). Many design-for-trust techniques have been proposed to detect HTs through observing erroneous output or abnormal side-channel characteristics. Side-channel characteristics such as path delay have been widely used for HT detection and functionality verification, as the changes of the characteristics of the host circuit incurred by the inserted HT can be identified through proper methods.
In this article, for the first time, we propose a two-phase technique, which uses the order of the path delay in path pairs to detect HTs. In the design phase, a full-cover path set that covers all the nets of the design is generated; meanwhile, in the set, the relative order of paths in path pairs is determined according to their delay. The order of the paths in path pairs serves as the fingerprint of the design. In the test phase, the actual delay of the paths in the full-cover set is extracted from the fabricated circuits, and the order of paths in path pairs is compared with the fingerprint generated in the design phase. A mismatch between them indicates the existence of HTs. Both process variations and measurement noise are taken into consideration. The efficiency and accuracy of the proposed technique are confirmed by a series of experiments, including the examination of both violated path pairs incurred by HTs and their false alarm rate.
Virtual machine design for parallel dynamic programming languages
Authors: Meier Remigius , Rigo Armin , Gross Thomas R. 
Published: October 2018

To leverage the benefits of modern hardware, dynamic languages must support parallelism, and parallelism requires a virtual machine (VM) capable of parallel execution — a parallel VM. However, unrestricted concurrency and the dynamism of dynamic languages pose great challenges to the implementation of parallel VMs. In a dynamic language, a program changing itself is part of the language model. To help the VM, languages often choose memory models (MM) that weaken consistency guarantees. With lesser guarantees, local program state cannot be affected by every concurrent state change. And less interference allows a VM to make local assumptions about the program state which are not immediately violated. These local assumptions are essential for a VM’s just-in-time compiler for delivering state-of-the-art VM performance.
Unfortunately, some dynamic languages employ MMs that give exceedingly strong consistency guarantees and thereby hinder the development of parallel VMs. Such is the case in particular for languages that depend on a global interpreter lock, which mandates a MM with sequential consistency and instruction atomicity.
In this paper, we reflect on a first implementation of the Parallel RPython execution model, which facilitates the development of parallel VMs by decoupling language semantics from the synchronization mechanism used within the VM. The implementation addresses the challenges imposed by strong MMs through strict isolation of concurrent computations. This isolation builds on transactional parallel worlds, which are implemented with a novel combination of software techniques and the capabilities of modern hardware.
We evaluate a set of parallel Python programs on a parallel VM that relies on Parallel RPython’s implementation. Compared with a serial baseline VM that relies on a global interpreter lock, the parallel VM achieves speedups of up to 7.5× on 8 CPU cores. The evaluation shows that our realization of Parallel RPython meets the challenges of dynamic languages, and that it can serve as a solid foundation for the construction of parallel dynamic language VMs.
Secure serverless computing using dynamic information flow control
Authors: Alpernas Kalev , Flanagan Cormac , Fouladi Sadjad , Ryzhyk Leonid , Sagiv Mooly , Schmitz Thomas , Winstein Keith 
Published: October 2018

The rise of serverless computing provides an opportunity to rethink cloud security. We present an approach for securing serverless systems using a novel form of dynamic information flow control (IFC).
We show that in serverless applications, the termination channel found in most existing IFC systems can be arbitrarily amplified via multiple concurrent requests, necessitating a stronger termination-sensitive non-interference guarantee, which we achieve using a combination of static labeling of serverless processes and dynamic faceted labeling of persistent data.
We describe our implementation of this approach on top of JavaScript for AWS Lambda and OpenWhisk serverless platforms, and present three realistic case studies showing that it can enforce important IFC security properties with modest overhead.
AnyDSL: a partial evaluation framework for programming high-performance libraries
Authors: Leißa Roland , Boesche Klaas , Hack Sebastian , Pérard-Gayot Arsène , Membarth Richard , Slusallek Philipp , Müller André , Schmidt Bertil 
Published: October 2018

This paper advocates programming high-performance code using partial evaluation. We present a clean-slate programming system with a simple, annotation-based, online partial evaluator that operates on a CPS-style intermediate representation. Our system exposes code generation for accelerators (vectorization/parallelization for CPUs and GPUs) via compiler-known higher-order functions that can be subjected to partial evaluation. This way, generic implementations can be instantiated with target-specific code at compile time.
In our experimental evaluation we present three extensive case studies from image processing, ray tracing, and genome sequence alignment. We demonstrate that using partial evaluation, we obtain high-performance implementations for CPUs and GPUs from one language and one code base in a generic way. The performance of our codes is mostly within 10%, often closer to the performance of multi man-year, industry-grade, manually-optimized expert codes that are considered to be among the top contenders in their fields.
GraphIt: a high-performance graph DSL
Authors: Zhang Yunming , Yang Mengjiao , Baghdadi Riyadh , Kamil Shoaib , Shun Julian , Amarasinghe Saman 
Published: October 2018

The performance bottlenecks of graph applications depend not only on the algorithm and the underlying hardware, but also on the size and structure of the input graph. As a result, programmers must try different combinations of a large set of techniques, which make tradeoffs among locality, work-efficiency, and parallelism, to develop the best implementation for a specific algorithm and type of graph. Existing graph frameworks and domain specific languages (DSLs) lack flexibility, supporting only a limited set of optimizations.
This paper introduces GraphIt, a new DSL for graph computations that generates fast implementations for algorithms with different performance characteristics running on graphs with different sizes and structures. GraphIt separates what is computed (algorithm) from how it is computed (schedule). Programmers specify the algorithm using an algorithm language, and performance optimizations are specified using a separate scheduling language. The algorithm language simplifies expressing the algorithms, while exposing opportunities for optimizations. We formulate graph optimizations, including edge traversal direction, data layout, parallelization, cache, NUMA, and kernel fusion optimizations, as tradeoffs among locality, parallelism, and work-efficiency. The scheduling language enables programmers to easily search through this complicated tradeoff space by composing together a large set of edge traversal, vertex data layout, and program structure optimizations. The separation of algorithm and schedule also enables us to build an autotuner on top of GraphIt to automatically find high-performance schedules. The compiler uses a new scheduling representation, the graph iteration space, to model, compose, and ensure the validity of the large number of optimizations. We evaluate GraphIt’s performance with seven algorithms on graphs with different structures and sizes. GraphIt outperforms the next fastest of six state-of-the-art shared-memory frameworks (Ligra, Green-Marl, GraphMat, Galois, Gemini, and Grazelle) on 24 out of 32 experiments by up to 4.8×, and is never more than 43% slower than the fastest framework on the other experiments. GraphIt also reduces the lines of code by up to an order of magnitude compared to the next fastest framework.
Bidirectional evaluation with direct manipulation
Authors: Mayer Mikaël , Kuncak Viktor , Chugh Ravi 
Published: October 2018

We present an evaluation update (or simply, update) algorithm for a full-featured functional programming language, which synthesizes program changes based on output changes. Intuitively, the update algorithm retraces the steps of the original evaluation, rewriting the program as needed to reconcile differences between the original and updated output values. Our approach, furthermore, allows expert users to define custom lenses that augment the update algorithm with more advanced or domain-specific program updates.
To demonstrate the utility of evaluation update, we implement the algorithm in Sketch-n-Sketch, a novel direct manipulation programming system for generating HTML documents. In Sketch-n-Sketch, the user writes an ML-style functional program to generate HTML output. When the user directly manipulates the output using a graphical user interface, the update algorithm reconciles the changes. We evaluate bidirectional evaluation in Sketch-n-Sketch by authoring ten examples comprising approximately 1400 lines of code in total. These examples demonstrate how a variety of HTML documents and applications can be developed and edited interactively in Sketch-n-Sketch, mitigating the tedious edit-run-view cycle in traditional programming environments.
Robust relational layout synthesis from examples for Android
Authors: Bielik Pavol , Fischer Marc , Vechev Martin 
Published: October 2018

We present a novel approach for synthesizing robust relational layouts from examples. Given an application design consisting of a set of views and their location on the screen, we synthesize a relational layout that when rendered, places the components at that same location.
We present an end-to-end system, called InferUI, that addresses the above challenge in the context of Android. The system is based on the following technical contributions: (i) a formalization of the latest and most efficient ConstraintLayout class, capturing a rich set of relational constraints, (ii) a set of robustness properties designed to prevent common layout generalization errors, (iii) a synthesis algorithm that produces relational layouts that generalize across multiple screen sizes and resolutions, and (iv) a probabilistic model of constraints that guides the synthesizer towards layouts preferred by developers.
Our evaluation shows that InferUI is practically effective: it successfully synthesizes real world complex layouts obtained from top 500 GitHub and top 500 Google Play Store applications, succeeds in 100% of the cases when synthesizing layouts for a single device, and correctly generalizes 92% of the views across multiple devices, all without requiring additional specifications.
Experimental Study on the Permeability of Weakly Cemented Rock under Different Stress States in Triaxial Compression Tests
Authors: Fan Gangwei , Chen Mingwei , Zhang Dongsheng , Wang Zhen , Zhang Shizhong , Zhang Chengguo , Li Qizhen , Cao Bobo 
Published: October 2018

Mudstone and shaly coarse sandstone samples of Jurassic units in northwestern China were collected to study the seepage mechanism of weakly cemented rock affected by underground mining operations. Samples were studied using seepage experiments under triaxial compression considering two processes: complete stress-strain and postpeak loading and unloading. The results show that permeability variations closely correspond to deviatoric stress-axial strain during the process of complete stress-strain. The initial permeability is 7 times its minimum, contrasting with lesser differentials of initial, peak, and residual permeability. The magnitude of permeability ranges from 10−17 to 10−19 m2, representing a stable water-resisting property, and is 1 to 2 orders lower in mudstone than that in shaly coarse sandstone, indicating that the water-resisting property of the mudstone is much better than that of the shaly coarse sandstone. Permeability is negatively correlated with the confining pressure. In response to this pressure, the permeability change in mudstone is faster than that in shaly coarse sandstone during the process of postpeak loading and unloading. Weakly cemented rock has lower permeability according to the comparison with congeneric ordinary rocks. This distinction is more remarkable in terms of the initial permeability. Analyses based on scanning electron microscope (SEM) observations and mineral composition indicate that the samples are rich in clay minerals such as montmorillonite and kaolin, whose inherent properties of hydroexpansiveness and hydrosliming can be considered the dominant factors contributing to the seepage properties of weakly cemented rock with low permeability.
PIN1 Maintains Redox Balance via the c-Myc/NRF2 Axis to Counteract Kras-Induced Mitochondrial Respiratory Injury in Pancreatic Cancer Cells
Authors: Liang Chen , Shi Si , Liu Mingyang , Qin Yi , Meng Qingcai , Hua Jie , Ji Shunrong , Zhang Yuqing , Yang Jingxuan , Xu Jin , Ni Quanxing , Li Min , Yu Xianjun 
Published: October 2018

Abstract

Kras is a decisive oncogene in pancreatic ductal adenocarcinoma (PDAC). PIN1 is a key effector involved in the Kras/ERK axis, synergistically mediating various cellular events. However, the underlying mechanism by which PIN1 promotes the development of PDAC remains unclear. Here we sought to elucidate the effect of PIN1 on redox homeostasis in Kras-driven PDAC. PIN1 was prevalently upregulated in PDAC and predicted the prognosis of the disease, especially Kras-mutant PDAC. Downregulation of PIN1 inhibited PDAC cell growth and promoted apoptosis, partially due to mitochondrial dysfunction. Silencing of PIN1 damaged basal mitochondrial function by significantly increasing intracellular ROS. Furthermore, PIN1 maintained redox balance via synergistic activation of c-Myc and NRF2 to upregulate expression of antioxidant response element driven genes in PDAC cells. This study elucidates a new mechanism by which Kras/ERK/NRF2 promotes tumor growth and identifies PIN1 as a decisive target in therapeutic strategies aimed at disturbing the redox balance in pancreatic cancer.

Significance:
This study suggests that antioxidation protects Kras-mutant pancreatic cancer cells from oxidative injury, which may contribute to development of a targeted therapeutic strategy for Kras-driven PDAC by impairing redox homeostasis.
Sleeping Beauty Screen Identifies RREB1 and Other Genetic Drivers in Human B-cell Lymphoma
Authors: Rahrmann Eric P. , Wolf Natalie K. , Otto George M. , Heltemes-Harris Lynn , Ramsey Laura B. , Shu Jingmin , LaRue Rebecca S. , Linden Michael A. , Rathe Susan K. , Starr Timothy K. , Farrar Michael A. , Moriarity Branden S. , Largaespada David A. 
Published: October 2018

Abstract

Follicular lymphoma and diffuse large B-cell lymphoma (DLBCL) are the most common non-Hodgkin lymphomas distinguishable by unique mutations, chromosomal rearrangements, and gene expression patterns. Here, it is demonstrated that early B-cell progenitors express 2′,3′-cyclic-nucleotide 3′ phosphodiesterase (CNP) and that when targeted with Sleeping Beauty (SB) mutagenesis, Trp53R270H mutation or Pten loss gave rise to highly penetrant lymphoid diseases, predominantly follicular lymphoma and DLBCL. In efforts to identify the genetic drivers and signaling pathways that are functionally important in lymphomagenesis, SB transposon insertions were analyzed from splenomegaly specimens of SB-mutagenized mice (n = 23) and SB-mutagenized mice on a Trp53R270H background (n = 7) and identified 48 and 12 sites with statistically recurrent transposon insertion events, respectively. Comparison with human data sets revealed novel and known driver genes for B-cell development, disease, and signaling pathways: PI3K–AKT–mTOR, MAPK, NFκB, and B-cell receptor (BCR). Finally, functional data indicate that modulating Ras-responsive element-binding protein 1 (RREB1) expression in human DLBCL cell lines in vitro alters KRAS expression, signaling, and proliferation; thus, suggesting that this proto-oncogene is a common mechanism of RAS/MAPK hyperactivation in human DLBCL.

Implications:
A forward genetic screen identified new genetic drivers of human B-cell lymphoma and uncovered a RAS/MAPK–activating mechanism not previously appreciated in human lymphoid disease. Overall, these data support targeting the RAS/MAPK pathway as a viable therapeutic target in a subset of human patients with DLBCL.
Triflamp, a snake venom metalloproteinase, reduces neutrophil-platelet adhesion through proteolysis of PSGL-1 but not glycoprotein Ibα
Authors: Tseng Yu-Lun , Lee Chia-Jung , Hsu Chun-Chieh , Huang Tur-Fu 
Published: October 2018

SummaryTriflamp, a metalloproteinase isolated from Trimeresurus flavoviridis, inhibits heterotypic adhesion between platelets and neutrophils. Coincubation studies demonstrate that direct interaction of triflamp with neutrophils is sufficient to inhibit the formation of neutrophil-platelet complexes. Its anti-adhesive effect is in a concentrationand incubation time-dependent manner. Triflamp reduces the expression of P-selectin glycoprotein ligand-1 (PSGL-1) on neutrophils and glycoprotein (GP) Ibα on platelets as probed by flow cytometry and Western blot. Moreover, triflamp disrupts P-selectin-mediated adhesion by cleaving PSGL-1 from the neutrophil surface.There are obvious differences regarding PSGL-1 proteolysis by triflamp and cathepsin G. Besides the NH2-terminus of PSGL-1, other sites are truncated by triflamp. The inhibitory effect of triflamp on PSGL-1 expression was prevented by pretreatment with a metalloproteinase inhibitor, phenanthroline. However, triflamptreated platelets fully keep the ability for binding to PAFor fMLP-stimulated neutrophils. Our results indicate that degradation of platelet GPIbα by triflamp does not interfere with neutrophil-platelet adhesion. Its effect on neutrophil PSGL-1 appears to be a critical factor for its inhibition on neutrophilplatelet interaction.
Pharmacokinetic Modelling to Predict FVIII:C Response to Desmopressin and Its Reproducibility in Nonsevere Haemophilia A Patients
Authors: Schütte Lisette , van Hest Reinier , Stoof Sara , Leebeek Frank , Cnossen Marjon , Kruip Marieke , Mathôt Ron 
Published: October 2018

Background Nonsevere haemophilia A (HA) patients can be treated with desmopressin. Response of factor VIII activity (FVIII:C) differs between patients and is difficult to predict.
Objectives Our aims were to describe FVIII:C response after desmopressin and its reproducibility by population pharmacokinetic (PK) modelling.
Patients and Methods Retrospective data of 128 nonsevere HA patients (age 7–75 years) receiving an intravenous or intranasal dose of desmopressin were used. PK modelling of FVIII:C was performed by nonlinear mixed effect modelling. Reproducibility of FVIII:C response was defined as less than 25% difference in peak FVIII:C between administrations.
Results A total of 623 FVIII:C measurements from 142 desmopressin administrations were available; 14 patients had received two administrations at different occasions. The FVIII:C time profile was best described by a two-compartment model with first-order absorption and elimination. Interindividual variability of the estimated baseline FVIII:C, central volume of distribution and clearance were 37, 43 and 50%, respectively. The most recently measured FVIII:C (FVIII-recent) was significantly associated with FVIII:C response to desmopressin (p < 0.001). Desmopressin administration resulted in an absolute FVIII:C increase of 0.47 IU/mL (median, interquartile range: 0.32–0.65 IU/mL, n = 142). FVIII:C response was reproducible in 6 out of 14 patients receiving two desmopressin administrations.
Conclusion FVIII:C response to desmopressin in nonsevere HA patients was adequately described by a population PK model. Large variability in FVIII:C response was observed, which could only partially be explained by FVIII-recent. FVIII:C response was not reproducible in a small subset of patients. Therefore, monitoring FVIII:C around surgeries or bleeding might be considered. Research is needed to study this further.
Treatment Challenges in Venous Thromboembolism: An Appraisal of Rivaroxaban Studies
Authors: Weitz Jeffrey , Khorana Alok 
Published: October 2018

AbstractVenous thromboembolism (VTE) presents a continuing clinical burden to healthcare systems and there are patient groups for whom VTE management is challenging. Depending on the patient profile, the optimal duration of anticoagulation for VTE treatment can be unclear. EINSTEIN CHOICE was a Phase III, randomized, double-blind trial that compared the safety and efficacy of two once-daily (od) doses of the direct, oral factor Xa inhibitor rivaroxaban (20 and 10 mg) with acetylsalicylic acid (ASA; 100 mg daily) for prevention of recurrent VTE. Extended therapy with rivaroxaban at either dose was more effective than ASA at preventing recurrent VTE without increasing bleeding risk. Another group that is challenging to treat in the context of VTE is patients with cancer-associated thrombosis. Cancer is associated with a hypercoagulable state, while cancer treatment itself may increase VTE risk. Evidence supporting the use of non-vitamin K antagonist oral anticoagulants in patients with cancer is growing through specifically designed studies. Cancer Associated thrombosis—expLoring soLutions for patIentS through Treatment and prevention with rivarOxaban (CALLISTO) is an international research program exploring the role of rivaroxaban for the prevention and treatment of cancer-associated thrombosis. Here, we present overviews of three CALLISTO studies: PRO-LAPS II, CASTA-DIVA and COSIMO. Currently available and anticipated results from studies in a variety of patients at risk of or with VTE will provide valuable insights and seek to optimize future VTE management.