bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Renal Failure on Ciprofloxacin Pharmacokinetics in Rats
Authors: Nouaille-Degorce B. , Veau C. , Dautrey S. , Tod M. , Laouari D. , Carbon C. , Farinotti R.
Published: April 2020

Ciprofloxacin pharmacokinetics have been shown to be modified in patients with renal failure (e.g., the intestinal secretion of ciprofloxacin is increased). This study investigated the influence of renal failure on the pharmacokinetics of ciprofloxacin following oral and parenteral administration to rats of a dose of 50 mg/kg of body weight. After parenteral administration, only renal clearance (CL
R
) was reduced in nephrectomized rats (5.3 ± 1.4 versus 17.8 ± 4.7 ml/min/kg,
P
< 0.01, nephrectomized versus control rats). However, nonrenal clearance was increased in nephrectomized rats (32 ± 4 versus 15 ± 5 ml/min/kg,
P
< 0.01, nephrectomized versus control rats), suggesting compensatory mechanisms for reduced renal function. After oral administration, apparent total clearance and CL
R
were reduced (
P
< 0.01) in nephrectomized rats (117 ± 25 and 6.8 ± 4.4 ml/min/kg, respectively) compared with the values for control rats (185 ± 9 and 22.6 ± 5.3 ml/min/kg, respectively) and the area under the concentration-time curve was higher (
P
< 0.01) for nephrectomized rats (436.3 ± 90.5 mg · min/liter) than for control rats (271.3 ± 14.3 mg · min/liter). Terminal elimination half lives in the two groups remained constant after oral and parenteral administration. These results suggest an increased bioavailability of ciprofloxacin in nephrectomized rats, which was confirmed by a nonlinear mixed-effect model.
Evaluation of the Safety and Pharmacokinetic Profile of a New, Pasteurized, Human Tetanus Immunoglobulin Administered as Sham, Postexposure Prophylaxis of Tetanus
Authors: Forrat Rémi , Dumas Rafaele , Seiberling Michael , Merz Michael , Lutsch Charles , Lang Jean
Published: April 2020

In a monocentric, double-blind, randomized trial, we examined the safety and pharmacokinetic profile of a new, pasteurized, human tetanus immunoglobulin (P-HTIG). As part of the purification process, P-HTIG has undergone a heat treatment step (10 h at 60°C) and the removal of Merthiolate. Forty-eight adults with a history of tetanus vaccination were randomized into four groups (n= 12 per group) to receive one of two different batches of this P-HTIG simultaneously with either tetanus-diphtheria (Td) vaccine (sham, postexposure prophylaxis of tetanus) or placebo. Local reactions at the injection site were followed for the first 3 days after injection, and systemic reactions were followed during the entire study period, i.e., up to 42 days posttreatment. Blood samples for tetanus antibody titer determination (enzyme-linked immunosorbent assay method) were drawn prior to treatment on day 0 and on days 1, 2, 3, 7, 14, 21, 28, 35, and 42. A normalization of tetanus antibody titers (subtraction of the day 0 value for each subject at each time period) was performed to assess the additive effect of P-HTIG on tetanus antibody titers. The pharmacokinetic parameters were determined by both a compartmental analysis (modelization) and a noncompartmental analysis. No severe adverse reactions were reported. The rate of local reactions at the P-HTIG injection site was 27%. All local reactions were mild and resolved within 2 days. In contrast, local reactions at the vaccine injection site were seen in 79% of the subjects. The rate of systemic reactions was similar in the P-HTIG plus Td vaccine group (33%) and in the P-HTIG plus placebo group (21%), and all these reactions were mild. In the P-HTIG plus placebo group, tetanus antibody titers rose to a maximum of 0.313 ± 2.49 IU/ml after 4.4 days; in the P-HTIG plus Td vaccine group, a maximum concentration of 15.2 ± 2.42 IU/ml was reached 19 days postinjection. In both groups, 100% of the patients had seroprotective levels of tetanus antibodies (≥0.01 IU/ml) 2 days following treatment. An anamnestic response to Td vaccine appeared 7 days postimmunization. In conclusion, P-HTIG has a good safety and pharmacokinetic profile. Our results confirm that immunoglobulin should be associated with vaccine in the treatment of tetanus-prone wounds.
Antimicrobial Susceptibility of
Haemophilus influenzae
in the Respiratory Tracts of Patients with Cystic Fibrosis
Authors: Möller Lieke V. M. , Regelink Annette G. , Grasselier Henny , van Alphen Loek , Dankert Jacob
Published: April 2020

We analyzed the antimicrobial susceptibilities of
Haemophilus influenzae
isolates from 157 sputum specimens prospectively collected from 39 cystic fibrosis (CF) patients during a 2-year study. These isolates were characterized by random amplified polymorphic DNA analysis and major outer membrane protein (MOMP) analysis to identify
H. influenzae
strains and MOMP variants and to assess their persistence in the respiratory tract. Among the 247
H. influenzae
isolates, 16 (6.5%) produced β-lactamase. The 231 β-lactamase-negative isolates represented 85
H. influenzae
strains, 61 MOMP variants derived from 27 of these strains, and 85 persistent isolates identical to strains or MOMP variants. All β-lactamase-negative isolates were tested for susceptibility to ampicillin, amoxicillin-clavulanic acid, cefuroxime, cefotaxime, cefaclor, imipenem, tetracycline, and trimethoprim-sulfamethoxazole by disk diffusion testing. Eleven (13%)
H. influenzae
strains, 18 (30%) MOMP variants, and 30 (35%) persistent isolates were resistant to one or more of the antibiotics tested. Antimicrobial susceptibility was decreased among MOMP variants and persistent isolates compared to nonpersistent
H. influenzae
strains, and changes in susceptibility occurred irrespective of MOMP variation. We conclude that the decreased antimicrobial susceptibility of
H. influenzae
during persistence contributes to the poor eradication of
H. influenzae
from the respiratory tracts of CF patients.
Mechanism of Amphotericin B Resistance in
Leishmania donovani
Promastigotes
Authors: Mbongo Nicolas , Loiseau Philippe M. , Billion Marie A. , Robert-Gero Malka
Published: April 2020

Amphotericin B (AmB)-resistant
Leishmania donovani
promastigotes were selected by increasing drug pressure, and their biological features were compared with those of the wild-type parent strain. The 50% inhibitory concentration for resistant cells was 20 times higher than that for the wild-type. Resistance was stable after more than 40 passages in drug-free medium, and resistant promastigotes were infective to macrophages in vitro but lost their virulence in vivo. They had 2.5 times longer generation time, decreased AmB uptake, and increased AmB efflux in comparison to the wild type. Fluorescence measurement with a specific plasma membrane probe, 1-[4-(trimethylammonio)-1,6-diphenylhexa]-1,3,5-triene, showed increased membrane fluidity in drug-resistant promastigotes. Analysis of lipid composition showed that in resistant cells saturated fatty acids were prevalent, with stearic acid as the major fatty acid, and the major sterol was an ergosterol precursor, the cholesta-5, 7, 24-trien-3β-ol and not ergosterol as in the AmB-sensitive strain.
Zalcitabine Population Pharmacokinetics: Application of Radioimmunoassay
Authors: Adams John M. , Shelton Mark J. , Hewitt Ross G. , DeRemer Mary , DiFrancesco Robin , Grasela Thaddeus H. , Morse Gene D.
Published: April 2020

Zalcitabine population pharmacokinetics were evaluated in 44 human immunodeficiency virus-infected patients (39 males and 5 females) in our immunodeficiency clinic. Eighty-one blood samples were collected during routine clinic visits for the measurement of plasma zalcitabine concentrations by radioimmunoassay (1.84 ± 1.24 samples/patient; range, 1 to 6 samples/patient). These data, along with dosing information, age (38.6 ± 7.13 years), sex, weight (79.1 ± 15.0 kg), and estimated creatinine clearance (89.1 ± 21.5 ml/min), were entered into NONMEM to obtain population estimates for zalcitabine pharmacokinetic parameters (4). The standard curve of the radioimmunoassay ranged from 0.5 to 50.0 ng/ml. The observed concentrations of zalcitabine in plasma ranged from 2.01 to 8.57 ng/ml following the administration of doses of either 0.375 or 0.75 mg. A one-compartment model best fit the data. The addition of patient covariates did not improve the basic fit of the model to the data. Oral clearance was determined to be 14.8 liters/h (0.19 liter/h/kg; coefficient of variation [CV] = 23.8%), while the volume of distribution was estimated to be 87.6 liters (1.18 liters/kg; CV = 54.0%). We were also able to obtain individual estimates of oral clearance (range, 8.05 to 19.8 liters/h; 0.11 to 0.30 liter/h/kg) and volume of distribution (range, 49.2 to 161 liters; 0.43 to 1.92 liters/kg) of zalcitabine in these patients with the POSTHOC option in NONMEM. Our value for oral clearance agrees well with other estimates of oral clearance from traditional pharmacokinetic studies of zalcitabine and suggests that population methods may be a reasonable alternative to these traditional approaches for obtaining information on the disposition of zalcitabine.
Critical Importance of In Vivo Amoxicillin and Cefotaxime Concentrations for Synergy in Treatment of Experimental
Enterococcus faecalis
Endocarditis
Authors: Join-Lambert Olivier , Mainardi Jean-Luc , Cuvelier Catherine , Dautrey Sophie , Farinotti Robert , Fantin Bruno , Carbon Claude
Published: April 2020

The synergy between amoxicillin and cefotaxime against two strains of
Enterococcus faecalis
(JH2-2 and 6370) in vitro and in rabbit endocarditis was investigated. In vitro synergy was obtained only when amoxicillin concentrations were below the MBC and when cefotaxime concentrations were above 1 μg/ml. No synergy was observed in vivo, because of the short period of time during which these pharmacologic requirements were achieved.
Estimate of the Frequency of Human Immunodeficiency Virus Type 1 Protease Inhibitor Resistance within Unselected Virus Populations In Vitro
Authors: Tucker Simon P. , Stiebel Thomas R. , Potts Karen E. , Smidt Mary L. , Bryant Martin L.
Published: April 2020

The frequency of drug-resistant human immunodeficiency virus type 1 (HIV-1) variants in virus populations not previously exposed to drug was determined in vitro by using HIV-1
RF
and the protease inhibitor SC-55389A. Two variants with single mutations responsible for drug resistance (V82A and N88S) were quantifiably isolated after only one round of replication, yielding a crude frequency estimate of at least 1 SC-55389A-resistant variant per 3.5 × 10
5
wild-type infectious units.
Impact of the Beta-Glucan Test on Management of Intensive Care Unit Patients at Risk for Invasive Candidiasis
Authors: Kritikos Antonios , Poissy Julien , Croxatto Antony , Bochud Pierre-Yves , Pagani Jean-Luc , Lamoth Frederic
Published: April 2020

The 1,3-beta-
d
-glucan (BDG) test is used for the diagnosis of invasive candidiasis (IC) in intensive care units (ICUs). However, its utility for patient management is unclear. This study assessed the impact of BDG test results on therapeutic decisions. This was a single-center observational study conducted in an ICU over two 6-month periods. All BDG test requests for the diagnosis of IC were analyzed. Before the second period, the ICU physicians received a pocket card instruction (algorithm) for targeted BDG testing in high-risk patients.
Evaluation of the EDTA-Modified Carbapenem Inactivation Method for Detecting Metallo-β-Lactamase-Producing
Pseudomonas aeruginosa
Authors: Gill Christian M. , Lasko Maxwell J. , Asempa Tomefa E. , Nicolau David P.
Published: April 2020

The prevalence of carbapenem-resistant
Pseudomonas aeruginosa
is increasing. Identification of carbapenemase-producing
P. aeruginosa
will have therapeutic, epidemiological, and infection control implications. This study evaluated the performance of the EDTA-modified carbapenem inactivation method (eCIM) in tandem with the modified carbapenem inactivation method (mCIM) against a large collection of clinical
P. aeruginosa
isolates (
n
 = 103) to provide clinicians a phenotypic test that not only identifies carbapenemase production but also distinguishes between metallo-β-lactamase and serine-carbapenemase production in
P. aeruginosa
.
Long-lasting clinical, radiological and immunological remission of severe nasal polyposis by means of ‘reboot’ surgery
Authors: Malvezzi Luca , Pirola Francesca , De Virgilio Armando , Heffler Enrico
Published: April 2020

A 68-year-old woman with a long history of relapsing chronic rhinosinusitis with nasal polyps (CRSwNP) underwent a complete reboot surgery and nasal biopsy prior to and after surgery. Remarkable improvement of symptoms and no signs of mucosal oedema and no complaints of initially worsening nasal functions were still present 12 months after reboot surgery. Biopsy demonstrated an outstanding reduction in eosinophilic infiltration and re-epithelisation of nasal mucosa with normal features after reboot approach compared with previous surgeries. Therefore, reboot approach may become an effective instrument in plurioperated patients with CRSwNP who suffer from a nasal condition that is recalcitrant to pharmacological therapies and is unsatisfactorily treated by standard surgical techniques.
Embedded, hard, real-time systems with Ada
Authors: Rogers Pat
Published: April 2020

Development of real-time systems is expensive and difficult, in part because of low-level languages that force developers to use facilities that are ad hoc, incomplete, and not portable. The Real-Time Systems Annex of Ada 2005 (along with the language core) represents the state-of-the-art in realtime programming languages and offers an extensive set of standardized packages and facilities for this domain. In addition, the language-defined Ravenscar profile describes a tasking subset that is analyzable for both high-integrity and hard real-time applications, and is small enough for very tightly resource-constrained applications as well. This tutorial examines the packages and pragmas defined by the annex for direct application use, examines the Ravenscar profile, and provides detailed examples of how they both are meant to be applied.
Working towards DO-178C/ED-12C, DO-248C/ED-94C, and DO-278A/ED109A
Authors: Chelini James
Published: April 2020

A Joint Committee RTCA/SC205 and EUROCAE/WG71 has been working on the revision to DO-178B and related documents for several years. DO-178B was published over 17 years ago, and as software technology has evolved, so has the need to update this document. The new revision will be called DO-178C/ED-12C. This revised core document will have additional supplements to support new technologies, for example, Model based development, Object oriented technologies, and Formal methods. In addition, document DO-248B/ED-94B "Clarification of DO-178B", will be revised and so will DO-278, which addresses ground based systems. This presentation will describe the changes already agreed and those still being proposed for these documents, and explain some of the rationale behind these changes. These documents will become certification guidance material, and will affect all those involved in software for airplanes and related ground based systems.
A look at Ada from both sides now (a government, and a defense contractor perspective)
Authors: Smart Jay C.
Published: April 2020

The Ada programming language has had a remarkable history, and promises an even more remarkable future. In this keynote address, Dr. J. Smart from Raytheon will provide his perspective on both as seen from within government, and from within private industry. With the pervasive nature of computing, the trade-craft of contemporary software development has changed considerably in recent years. Arguably, not all the change has been for the better. What may have once been regarded as minor flaws or operational nuisances in software system implementations can now manifest in far more devastating ways, and with potentially severe consequences. The boundaries of Ada's "embedded system" niche are becoming increasingly difficult to discern from commodity software, particularly as the challenges of computer security compound. A critical need now exists for a much broader application of the unique culture and programming discipline that has naturally accompanied Ada for these many years.

Of particular personal research interest to the presenter is the new generation of reconfigurable computing systems and devices (e.g., FPGAs). The ability to specify a system from the highest level of abstraction all the way down to an individual gate level is now possible from within a single unified description framework. Ada is potentially the ideal choice for such a framework. The presenter will describes his experiences using Ada in this manner to design and implement a most unusual dynamic computing machine. In this application where reliability and formal verification is of upmost importance, the Ada language has been the major contributor to the effort's success.
Georegistration of imagery from unmanned aircraft systems using Ada
Authors: Sward Ricky E.
Published: April 2020

As Unmanned Aircraft Systems are used for an increasing number of applications, the challenge of precisely locating the geospatial position of imagery coming from the UAS is becoming more crucial. Through work that has been done in conjunction with the US Air Force Academy, Ada has been used to calculate the position and size of UAS imagery based on field-of-view calculations and elevation data. This paper describes the work that has been done this past year to georegister UAS imagery and how Ada has been used previously for this challenging task.
Transistors to toys
Authors: Chen Peter M.
Published: April 2020

How should we introduce students to the art of system building, and when are students ready to start designing and building interesting systems? In this talk, I describe an experimental course at the University of Michigan that teaches systems to freshmen by having them conceive of, design, and build the hardware and software of a microprocessor-based educational toy. Students in this course build their own microprocessor on an FPGA using a hardware description language. They then write the complete software stack for their toy in assembly language, including device drivers for numerous I/O devices, a simple file system, a graphical user interface, digital audio processing, and application software. By building a substantial system involving hardware, system software, and application software, students gain an appreciation for the complexity and beauty of building computing systems.
Capability wrangling made easy
Authors: Pohle Aaron , Döbel Björn , Roitzsch Michael , Härtig Hermann
Published: April 2020

Not all operating systems are created equal. Contrasting traditional monolithic kernels, there is a class of systems called microkernels more prevalent in embedded systems like cellphones, chip cards or real-time controllers. These kernels offer an abstraction very different from the classical POSIX interface. The resulting unfamiliarity for programmers complicates development and debugging. Valgrind is a well-known debugging tool that virtualizes execution to perform dynamic binary analysis. However, it assumes to run on a POSIX-like kernel and closely interacts with the system to control execution. In this paper we analyze how to adapt Valgrind to a non-POSIX environment and describe our port to the Fiasco.OC microkernel. Additionally, we analyze bug classes that are indigenous to capability systems and show how Valgrind's flexibility can be leveraged to create custom debugging tools detecting these errors.
Static analysis of aspect interaction and composition in component models
Authors: Hannousse Abdelhakim , Douence Rémi , Ardourel Gilles
Published: April 2020

Component based software engineering and aspect orientation are claimed to be two complementary approaches. While the former ensures the modularity and the reusability of software entities, the latter enables the modularity of crosscutting concerns that cannot be modularized as regular components. Nowadays, several approaches and frameworks are dedicated to integrate aspects into component models. However, when several aspects are woven, aspects may interact with each other which often results in undesirable behavior. The contribution of this paper is twofold. First, we show how aspectized component models can be formally modeled in UPPAAL model checker in order to detect negative interactions (a.k.a., interferences) among aspects. Second, we provide an extendible catalog of composition operators used for aspect composition. We illustrate our general approach with an airport Internet service example.
Pragmatics for formal semantics
Authors: Danvy Olivier
Published: April 2020

This tech talk describes how to write and how to inter-derive formal semantics for sequential programming languages. The progress reported here is (1) concrete guidelines to write each formal semantics to alleviate their proof obligations, and (2) simple calculational tools to obtain a formal semantics from another.
Lightweight generics in embedded systems through static analysis
Authors: Sallenave Olivier , Ducournau Roland
Published: April 2020

Low-end embedded systems are still programmed in C and assembly, and adopting high-level languages such as C# should reduce the length of their development cycles. For these systems, code size is a major concern, but run-time efficiency should also be reasonable --- programmers will not migrate to C# unless the overhead compared with C is insignificant. In this paper, we propose a static approach based on whole program optimization for implementing .Net generics in such systems. Indeed, the implementation of run-time generics involves a tradeoff between size and run-time efficiency. In this proposal, generic instances are detected through a generalization of RTA to parametric polymorphism. Also, we propose an implementation scheme which employs code sharing and more effective coercions than boxing. Unlike existing implementation schemes, it is scalable in the number of generic instances without involving boxing and unboxing in a systematic way.
Profile-guided deployment of stream programs on multicores
Authors: Farhad S. M. , Ko Yousun , Burgstaller Bernd , Scholz Bernhard
Published: April 2020

Because multicore architectures have become the industry standard, programming abstractions for concurrent programming are of key importance. Stream programming languages facilitate application domains characterized by regular sequences of data, such as multimedia, graphics, signal processing and networking. With stream programs, computations are expressed through independent actors that interact through FIFO data channels. A major challenge with stream programs is to load-balance actors among available processing cores. The workload of a stream program is determined by actor execution times and the communication overhead induced by data channels. Estimating communication costs on cache-coherent shared-memory multiprocessors is difficult, because data movements are abstracted away by the cache coherence protocol. Standard execution time profiling techniques cannot separate actor execution times from communication costs, because communication costs manifest in terms of execution time overhead.

In this work we present a unified Integer Linear Programming (ILP) formulation that balances the workload of stream programs on cache-coherent multicore architectures. For estimating the communication costs of data channels, we devise a novel profiling scheme that minimizes the number of profiling steps. We conduct experiments across a range of StreamIt benchmarks and show that our method achieves a speedup of up to 4.02x on 6 processors. The number of profiling steps is on average only 17% of an exhaustive profiling run over all data channels of a stream program.
Improving dynamic prediction accuracy through multi-level phase analysis
Authors: Fang Zhenman , Li Jiaxin , Zhang Weihua , Li Yi , Chen Haibo , Zang Binyu
Published: April 2020

Phase analysis, which classifies the set of execution intervals with similar execution behavior and resource requirements, has been widely used in a variety of dynamic systems, including dynamic cache reconfiguration, prefetching and race detection. While phase granularity has been a major factor to the accuracy of phase prediction, it has not been well investigated yet and most dynamic systems usually adopt a fine-grained prediction scheme. However, such a scheme can only take account of recent local phase information and could be frequently interfered by temporary noises due to instant phase changes, which might notably limit the prediction accuracy.

In this paper, we make the first investigation on the potential of multi-level phase analysis (MLPA), where different granularity phase analysis are combined together to improve the overall accuracy. The key observation is that a coarse-grained interval, which usually consists of
stably-distributed
fine-grained intervals, can be accurately identified based on the fine-grained intervals at the beginning of its execution. Based on the observation, we design and implement a MLPA scheme. In such a scheme, a coarse-grained phase is first identified based on the fine-grained intervals at the beginning of its execution. The following fine-grained phases in it are then predicted based on the sequence of fine-grained phases in the coarse-grained phase. Experimental results show such a scheme can notably improve the prediction accuracy. Using Markov fine-grained phase predictor as the baseline, MLPA can improve prediction accuracy by 20%, 39% and 29% for next phase, phase change and phase length prediction for SPEC2000 accordingly, yet incur only about 2% time overhead and 40% space overhead (about 360 bytes in total).

To demonstrate the effectiveness of MLPA, we apply it to a dynamic cache reconfiguration system which dynamically adjusts the cache size to reduce the power consumption and access time of data cache. Experimental results show that MLPA can further reduce the average cache size by 15% compared to the fine-grained scheme.
Hilt'12 tutorial overview / design of multitask software
Authors: Sandén Bo I.
Published: April 2020

The tutorial introduces entity-life modeling (ELM), a design approach for multitask, reactive software. It is not a multistep method but rather an extension of object orientation into the time dimension: The central idea is that the task architecture should reflect concurrency that exists in the problem. The tutorial uses Ada terminology and is illustrated with multiple Ada examples.
Leading-edge Ada verification technologies
Authors: Belt Jason , Chalin Patrice , Hatcliff John , Robby
Published: April 2020

This tutorial presents a new approach to Spark/Ada contract checking using Bakar Kiasan--a highly automated, evidence-based symbolic execution tool. Bakar Kiasan aims to lower the barrier of entry and reduce the burden of engineers as they specify and verify Ada contracts. Even in the absence of contracts, Bakar Kiasan can check code for possible runtime exceptions and provide visualizations of semantic constraints along paths through procedures. As engineers progressively add contracts, Bakar Kiasan can verify the consistency of code and contracts, thus providing increased confidence, often proportional to the efforts made to capture fuller behavioral specifications via contracts. Bakar Kiasan also provides compositional checking; that is, it can be used on incomplete systems, where contracts are only present for some program components (which may not even have been implemented). This allows contract checking to be used as the program is being developed starting early in the software development process.

Bakar Kiasan provides helpful feedback and evidence of its verification results. For example, it automatically generates counter examples as program test cases for illustrating how contracts are violated (this is very helpful when debugging code/contracts), as well as providing various visualization cues, for example, highlighting problematic code or contract segments similar to how modern Integrated Development Environments (IDEs) illustrate compile (type) errors. Kiasan also generates test cases for illustrating how contracts are satisfied, which is helpful for understanding code/contracts or confirming how a program should behave. Bakar Kiasan is integrated in the Eclipse IDE as a plug-in, and an integration with the GNAT Programming Studio (GPS) is currently being developed in collaboration with AdaCore.
Applicability of real-time schedulability analysis on a software radio protocol
Authors: Li Shuai , Singhoff Frank , Rubini Stéphane , Michel Bourdellès
Published: April 2020

In this paper, we present our experience on integrating timing constraint verification and analysis, by using the real-time scheduling theory, in an industrial context. The verification process has been integrated into a design flow at THALES Communications & Security. We focus our work on Software Radio Protocols (SRP). We have used Model-Driven Engineering technologies and the Cheddar schedulability analysis tool for our experiment. We show how we have modeled a complete SRP in UML MARTE, a profile for real-time embedded systems, before using model transformation to extract information for schedulability analysis with Cheddar.
Reasoning of feature models from derived features
Authors: Ryssel Uwe , Ploennigs Joern , Kabitzsch Klaus
Published: April 2020

When using product lines, whose variability models are based on derived features, e.g., Simulink variant objects, the dependencies among the features are only described implicitly. This makes it difficult to verify the mapping of the features to the solution space and to create a comprehensive overview of the feature dependencies like in a feature model. In this paper, an OWL-based approach is presented, which permits the automatic verification of the feature mapping and an automatic feature model synthesis for derived features using OWL reasoning and formal concept analysis.
Composing typemaps in Twig
Authors: Hulette Geoffrey C. , Sottile Matthew , Malony Allen D.
Published: April 2020

Twig is a language for writing
typemaps
, programs which transform the type of a value while preserving its underlying meaning. Typemaps are typically used by tools that generate code, such as multi-language wrapper generators, to automatically convert types as needed. Twig builds on existing typemap tools in a few key ways. Twig's typemaps are composable so that complex transformations may be built from simpler ones. In addition, Twig incorporates an abstract, formal model of code generation, allowing it to output code for different target languages. We describe Twig's formal semantics and show how the language allows us to concisely express typemaps. Then, we demonstrate Twig's utility by building an example typemap.
Xbase
Authors: Efftinge Sven , Eysholdt Moritz , Köhnlein Jan , Zarnekow Sebastian , von Massow Robert , Hasselbring Wilhelm , Hanus Michael
Published: April 2020

Xtext is an open-source framework for implementing external, textual domain-specific languages (DSLs). So far, most DSLs implemented with Xtext and similar tools focus on structural aspects such as service specifications and entities. Because behavioral aspects are significantly more complicated to implement, they are often delegated to general-purpose programming languages. This approach introduces complex integration patterns and the DSL's high level of abstraction is compromised.

We present Xbase as part of Xtext, an expression language that can be reused via language inheritance in any DSL implementation based on Xtext. Xbase expressions provide both control structures and program expressions in a uniform way. Xbase is statically typed and tightly integrated with the Java type system. Languages extending Xbase inherit the syntax of a Java-like expression language as well as language infrastructure components, including a parser, an unparser, a linker, a compiler and an interpreter. Furthermore, the framework provides integration into the Eclipse IDE including debug and refactoring support.

The application of Xbase is presented by means of a domain model language which serves as a tutorial example and by the implementation of the programming language Xtend. Xtend is a functional and object-oriented general purpose language for the Java Virtual Machine (JVM). It is built on top of Xbase which is the reusable expression language that is the foundation of Xtend.
Preference and artifact analysis for video transitions of places
Authors: Tompkin James , Kim Min H. , Kim Kwang In , Kautz Jan , Theobalt Christian
Published: April 2020

Emerging interfaces for video collections of places attempt to link similar content with seamless transitions. However, the automatic computer vision techniques that enable these transitions have many failure cases which lead to artifacts in the final rendered transition. Under these conditions, which transitions are preferred by participants and which artifacts are most objectionable? We perform an experiment with participants comparing seven transition types, from movie cuts and dissolves to image-based warps and virtual camera transitions, across five scenes in a city. This document describes how we condition this experiment on slight and considerable view change cases, and how we analyze the feedback from participants to find their preference for transition types and artifacts. We discover that transition preference varies with view change, that automatic rendered transitions are significantly preferred even with some artifacts, and that dissolve transitions are comparable to less-sophisticated rendered transitions. This leads to insights into what visual features are important to maintain in a rendered transition, and to an artifact ordering within our transitions.
Parametric completeness for separation theories
Authors: Brotherston James , Villard Jules
Published: April 2020

In this paper, we close the logical gap between provability in the logic BBI, which is the propositional basis for
separation logic
, and validity in an intended class of
separation models
, as employed in applications of separation logic such as program verification. An intended class of separation models is usually specified by a collection of axioms describing the specific model properties that are expected to hold, which we call a
separation theory
.

Our main contributions are as follows. First, we show that several typical properties of separation theories are not definable in BBI. Second, we show that these properties become definable in a suitable
hybrid extension
of BBI, obtained by adding a theory of
naming
to BBI in the same way that
hybrid logic
extends normal modal logic. The binder-free extension captures most of the properties we consider, and the full extension HyBBI(↓) with the usual ↓ binder of hybrid logic covers all these properties. Third, we present an axiomatic proof system for our hybrid logic whose extension with any set of "pure" axioms is sound and complete with respect to the models satisfying those axioms. As a corollary of this general result, we obtain, in a parametric manner, a sound and complete axiomatic proof system for any separation theory from our considered class. To the best of our knowledge, this class includes all separation theories appearing in the published literature.
Bias-variance tradeoffs in program analysis
Authors: Sharma Rahul , Nori Aditya V. , Aiken Alex
Published: April 2020

It is often the case that increasing the precision of a program analysis leads to worse results. It is our thesis that this phenomenon is the result of fundamental limits on the ability to use precise abstract domains as the basis for inferring strong invariants of programs. We show that
bias-variance tradeoffs
, an idea from learning theory, can be used to explain why more precise abstractions do not necessarily lead to better results and also provides practical techniques for coping with such limitations. Learning theory captures precision using a combinatorial quantity called the
VC dimension
. We compute the VC dimension for different abstractions and report on its usefulness as a precision metric for program analyses. We evaluate
cross validation
, a technique for addressing bias-variance tradeoffs, on an industrial strength program verification tool called YOGI. The tool produced using cross validation has significantly better running time, finds new defects, and has fewer time-outs than the current production version. Finally, we make some recommendations for tackling bias-variance tradeoffs in program analysis.
Closed type families with overlapping equations
Authors: Eisenberg Richard A. , Vytiniotis Dimitrios , Peyton Jones Simon , Weirich Stephanie
Published: April 2020

Open, type-level functions are a recent innovation in Haskell that move Haskell towards the expressiveness of dependent types, while retaining the look and feel of a practical programming language. This paper shows how to increase expressiveness still further, by adding closed type functions whose equations may overlap, and may have non-linear patterns over an open type universe. Although practically useful and simple to implement, these features go
beyond
conventional dependent type theory in some respects, and have a subtle metatheory.
Bridging boolean and quantitative synthesis using smoothed proof search
Authors: Chaudhuri Swarat , Clochard Martin , Solar-Lezama Armando
Published: April 2020

We present a new technique for parameter synthesis under boolean and quantitative objectives. The input to the technique is a "sketch" --- a program with missing numerical parameters --- and a probabilistic assumption about the program's inputs. The goal is to automatically synthesize values for the parameters such that the resulting program satisfies: (1) a {boolean specification}, which states that the program must meet certain assertions, and (2) a {quantitative specification}, which assigns a real valued rating to every program and which the synthesizer is expected to optimize.

Our method --- called
smoothed proof search
--- reduces this task to a sequence of unconstrained smooth optimization problems that are then solved numerically. By iteratively solving these problems, we obtain parameter values that get closer and closer to meeting the boolean specification; at the limit, we obtain values that provably meet the specification. The approximations are computed using a new notion of
smoothing
for program abstractions, where an abstract transformer is approximated by a function that is continuous according to a metric over abstract states.

We present a prototype implementation of our synthesis procedure, and experimental results on two benchmarks from the embedded control domain. The experiments demonstrate the benefits of smoothed proof search over an approach that does not meet the boolean and quantitative synthesis goals simultaneously.
On coinductive equivalences for higher-order probabilistic functional programs
Authors: Dal Lago Ugo , Sangiorgi Davide , Alberti Michele
Published: April 2020

We study bisimulation and context equivalence in a probabilistic lambda-calculus. The contributions of this paper are threefold. Firstly we show a technique for proving congruence of probabilistic applicative bisimilarity. While the technique follows Howe's method, some of the technicalities are quite different, relying on non-trivial "disentangling" properties for sets of real numbers. Secondly we show that, while bisimilarity is in general strictly finer than context equivalence, coincidence between the two relations is attained on pure lambda-terms. The resulting equality is that induced by Levy-Longo trees, generally accepted as the finest extensional equivalence on pure lambda-terms under a lazy regime. Finally, we derive a coinductive characterisation of context equivalence on the whole probabilistic language, via an extension in which terms akin to distributions may appear in redex position. Another motivation for the extension is that its operational semantics allows us to experiment with a different congruence technique, namely that of logical bisimilarity.
A type-directed abstraction refinement approach to higher-order model checking
Authors: Ramsay Steven J. , Neatherway Robin P. , Ong C.-H. Luke
Published: April 2020

The trivial-automaton model checking problem for higher-order recursion schemes has become a widely studied object in connection with the automatic verification of higher-order programs. The problem is formidably hard: despite considerable progress in recent years, no decision procedures have been demonstrated to scale robustly beyond recursion schemes that comprise more than a few hundred rewrite rules. We present a new, fixed-parameter polynomial time algorithm, based on a novel, type directed form of abstraction refinement in which behaviours of a scheme are distinguished by the abstraction according to the intersection types that they inhabit (the properties that they satisfy). Unlike other intersection type approaches, our algorithm reasons both about acceptance by the property automaton and acceptance by its dual, simultaneously, in order to minimize the amount of work done by converging on the solution to a problem instance from both sides. We have constructed Preface, a prototype implementation of the algorithm, and assembled an extensive body of evidence to demonstrate empirically that the algorithm readily scales to recursion schemes of several thousand rules, well beyond the capabilities of current state-of-the-art higher-order model checkers.
Fair reactive programming
Authors: Cave Andrew , Ferreira Francisco , Panangaden Prakash , Pientka Brigitte
Published: April 2020

Functional Reactive Programming (FRP) models reactive systems with events and signals, which have previously been observed to correspond to the "eventually" and "always" modalities of linear temporal logic (LTL). In this paper, we define a constructive variant of LTL with least fixed point and greatest fixed point operators in the spirit of the modal mu-calculus, and give it a proofs-as-programs interpretation as a foundational calculus for reactive programs. Previous work emphasized the propositions-as-types part of the correspondence between LTL and FRP; here we emphasize the proofs-as-programs part by employing structural proof theory. We show that the type system is expressive enough to enforce liveness properties such as the fairness of schedulers and the eventual delivery of results. We illustrate programming in this calculus using (co)iteration operators. We prove type preservation of our operational semantics, which guarantees that our programs are causal. We give also a proof of strong normalization which provides justification that our programs are productive and that they satisfy liveness properties derived from their types.
TeJaS
Authors: Lerner Benjamin S. , Politz Joe Gibbs , Guha Arjun , Krishnamurthi Shriram
Published: April 2020

JavaScript programs vary widely in functionality, complexity, and use, and analyses of these programs must accommodate such variations. Type-based analyses are typically the simplest such analyses, but due to the language's subtle idioms and many application-specific needs---such as ensuring general-purpose type correctness, security properties, or proper library usage---we have found that a single type system does not suffice for all purposes. However, these varied uses still share many reusable common elements.

In this paper we present TeJaS, a framework for building type systems for JavaScript. TeJaS has been engineered modularly to encourage experimentation. Its initial type environment is reified, to admit easy modeling of the various execution contexts of JavaScript programs, and its type language and typing rules are extensible, to enable variations of the type system to be constructed easily.

The paper presents the base TeJaS type system, which performs traditional type-checking for JavaScript. Because JavaScript demands complex types, we explain several design decisions to improve user ergonomics. We then describe TeJaS's modular structure, and illustrate it by reconstructing the essence of a very different type system for JavaScript. Systems built from TeJaS have been applied to several real-world, third-party JavaScript programs.
Type refinement for static analysis of JavaScript
Authors: Kashyap Vineeth , Sarracino John , Wagner John , Wiedermann Ben , Hardekopf Ben
Published: April 2020

Static analysis of JavaScript has proven useful for a variety of purposes, including optimization, error checking, security auditing, program refactoring, and more. We propose a technique called
type refinement
that can improve the precision of such static analyses for JavaScript without any discernible performance impact. Refinement is a known technique that uses the conditions in branch guards to refine the analysis information propagated along each branch path. The key insight of this paper is to recognize that JavaScript semantics include many implicit conditional checks on types, and that performing type refinement on these implicit checks provides significant benefit for analysis precision.

To demonstrate the effectiveness of type refinement, we implement a static analysis tool for reporting potential type-errors in JavaScript programs. We provide an extensive empirical evaluation of type refinement using a benchmark suite containing a variety of JavaScript application domains, ranging from the standard performance benchmark suites (Sunspider and Octane), to open-source JavaScript applications, to machine-generated JavaScript via Emscripten. We show that type refinement can significantly improve analysis precision by up to 86% without affecting the performance of the analysis.
Efficient dynamic access analysis using JavaScript proxies
Authors: Keil Matthias , Thiemann Peter
Published: April 2020

JSConTest introduced the notions of effect monitoring and dynamic effect inference for JavaScript. It enables the description of effects with path specifications resembling regular expressions. It is implemented by an offline source code transformation.

To overcome the limitations of the JSConTest implementation, we redesigned and reimplemented effect monitoring by taking advantange of JavaScript proxies. Our new design avoids all drawbacks of the prior implementation. It guarantees full interposition; it is not restricted to a subset of JavaScript; it is self-maintaining; and its scalability to large programs is significantly better than with JSConTest.

The improved scalability has two sources. First, the reimplementation is significantly faster than the original, transformation-based implementation. Second, the reimplementation relies on the fly-weight pattern and on trace reduction to conserve memory. Only the combination of these techniques enables monitoring and inference for large programs.
Constraint satisfaction problem and universal algebra
Authors: Barto Libor
Published: April 2020

This column gives a brief survey of current research on the complexity of the constraint satisfaction problem (CSP) over fixed constraint languages.
PROMPT -- Master Courses for Professional Software Developers
Authors: Eck Stefan , Hansson Hans A.
Published: April 2020

PROMPT [1] is an educational initiative in cooperation with several academic parties and leading industrial companies and organizations. Together, the parties offer advanced level courses in software engineering in a web-based format, tailored to fit professional engineers and software developers who need to be able to combine full-time work and studies. The long-term goal of PROMPT is to guarantee the supply of advanced software competencies and innovativeness in industry. The courses are free of charge within Europe, cover typically 7.5 university credits and are run over a whole semester, at a pace of 25% of full-time. All courses are developed in close cooperation with the Swedish industry and trade organizations.