Petr Hosek

Safe software updates via multi-version execution

Software systems are constantly evolving, with new versions and patches being released on a continuous basis. Unfortunately, software updates present a high risk, with many releases introducing new bugs and security vulnerabilities. We tackle this problem using a simple but effective multi-version based approach. Whenever a new update becomes available, instead of upgrading the software to the new version, we run the new version in parallel with the old one; by carefully coordinating their executions and selecting the behaviour of the more reliable version when they diverge, we create a more secure and dependable multi-version application. We implemented this technique in Mx, a system targeting Linux applications running on multi-core processors, and show that it can be applied successfully to several real applications such as Coreutils, a set of user-level UNIX applications; Lighttpd, a popular web server used by several high-traffic websites such as Wikipedia and YouTube; and Redis, an advanced key-value data structure server used by many well-known services such as GitHub and Flickr.

Comparison of component frameworks for real-time embedded systems

The use of components significantly helps in development of real-time embedded systems. There have been a number of component frameworks developed for this purpose, and some of them have already became well established in this area. Even though these frameworks share the general idea of component-based development, they significantly differ in the range of supported features and maturity. This makes it relatively difficult to select the right component framework and thus poses a significant obstacle in adoption of the component-based development approach for developing real-time embedded systems. To provide guidance in choosing a component framework, or at least relevant concepts when building a custom framework, we present a survey, which illustrates distinguishing features and provides comparison of selected modern component-based frameworks for real-time embedded systems. Compared to other existing surveys, this survey focuses specifically on criteria connected with real-time and embedded systems. Further, to be practically relevant, we restrict the survey only to the frameworks that support the full development life cycle (i.e. from design till execution support). In this context, the survey illustrates the complexity of development in each framework by giving specification and code samples.

Covrig: a framework for the analysis of code, test, and coverage evolution in real software

Software repositories provide rich information about the construction and evolution of software systems. While static data that can be mined directly from version control systems has been extensively studied, dynamic metrics concerning the execution of the software have received much less attention, due to the inherent difficulty of running and monitoring a large number of software versions. In this paper, we present Covrig, a flexible infrastructure that can be used to run each version of a system in isolation and collect static and dynamic software metrics, using a lightweight virtual machine environment that can be deployed on a cluster of local or cloud machines. We use Covrig to conduct an empirical study examining how code and tests co-evolve in six popular open-source systems. We report the main characteristics of software patches, analyse the evolution of program and patch coverage, assess the impact of nondeterminism on the execution of test suites, and investigate whether the coverage of code containing bugs and bug fixes is higher than average.

VARAN the Unbelievable: An Efficient N-version Execution Framework

With the widespread availability of multi-core processors, running multiple diversified variants or several different versions of an application in parallel is becoming a viable approach for increasing the reliability and security of software systems. The key component of such N-version execution (NVX) systems is a runtime monitor that enables the execution of multiple versions in parallel. Unfortunately, existing monitors impose either a large performance overhead or rely on intrusive kernel-level changes. Moreover, none of the existing solutions scales well with the number of versions, since the runtime monitor acts as a performance bottleneck. In this paper, we introduce Varan, an NVX framework that combines selective binary rewriting with a novel event-streaming architecture to significantly reduce performance overhead and scale well with the number of versions, without relying on intrusive kernel modifications. Our evaluation shows that Varan can run NVX systems based on popular C10k network servers with only a modest performance overhead, and can be effectively used to increase software reliability using techniques such as transparent failover, live sanitization and multi-revision execution.

Low molecular weight hyaluronan mediated CD44 dependent induction of IL-6 and chemokines in human dermal fibroblasts potentiates innate immune response

Complex regulation of the wound healing process involves multiple interactions among stromal tissue cells, inflammatory cells, and the extracellular matrix. Low molecular weight hyaluronan (LMW HA) derived from the degradation of high molecular weight hyaluronan (HMW HA) is suggested to activate cells involved in wound healing through interaction with HA receptors. In particular, receptor CD44 is suggested to mediate cell response to HA of different MW, being the main cell surface HA receptor in stromal tissue and immune cells. However, the response of dermal fibroblasts, the key players in granulation tissue formation within the wound healing process, to LMW HA and their importance for the activation of immune cells is unclear. In this study we show that LMW HA (4.3kDa) induced pro-inflammatory cytokine IL-6 and chemokines IL-8, CXCL1, CXCL2, CXCL6 and CCL8 gene expression in normal human dermal fibroblasts (NHDF) that was further confirmed by increased levels of IL-6 and IL-8 in cell culture supernatants. Conversely, NHDF treated by HMW HA revealed a tendency to decrease the gene expression of these cytokine and chemokines when compared to untreated control. The blockage of CD44 expression by siRNA resulted in the attenuation of IL-6 and chemokines expression in LMW HA treated NHDF suggesting the involvement of CD44 in LMW HA mediated NHDF activation. The importance of pro-inflammatory mediators produced by LMW HA triggered NHDF was evaluated by significant activation of blood leukocytes exhibited as increased production of IL-6 and TNF-α. Conclusively, we demonstrated a pro-inflammatory response of dermal fibroblasts to LMW HA that was transferred to leukocytes indicating the significance of LMW HA in the inflammatory process development during the wound healing process.

Immunohistochemical Detection of Cancer Stem Cell Related Markers CD44 and CD133 in Metastatic Colorectal Cancer Patients

Aim. The goal of this study was to semiquantitatively detect presence of cancer stem cells markers CD44 and CD133 in immunohistochemically stained paired samples of colorectal cancer (CRC) and colorectal liver metastases (CLM). Level of staining intensity was compared to clinical and pathological characteristics of tumors with the aim to identify impact of CD44 or CD133 expression on tumor behavior. Patients and Methods. Formalin fixed paraffin embedded samples from 94 patients with colorectal tumor and liver metastases were collected at Sikls Department of Pathology. Samples were stained by antibodies against CD44 and CD133. Presence and intensity of staining was assessed semiquantitatively by three trained researchers. Results. Patients with higher level of CD133 staining in CRC had longer disease free interval (Cox-Mantel P = 0.0244), whereas we found no relation between CD44 expression and overall survival or disease free interval. CD133 expression in CRC and CLM differed based on CRC grading; in case of CD44 we found differences in staining intensity in individual stages of tumor lymph node invasion. Conclusion. Effect of cancer stem cell markers on prognosis of colorectal cancer can vary depending on pathological classification of tumor, and we have shown that CD133, generally considered to be a negative marker, can bear also clinically positive prognostic information in group of patients with colorectal liver metastases.

The association of miR-126-3p, miR-126-5p and miR-664-3p expression profiles with outcomes of patients with metastatic colorectal cancer treated with bevacizumab

MicroRNAs regulate the expression of genes involved in several important cancer-related processes including cell adhesion, proliferation, and tumour angiogenesis. Bevacizumab is routinely used in the treatment of patients with metastatic colorectal cancer, but, so far, no reliable biomarker predicting response to bevacizumab has been established. The aim of our retrospective study was to evaluate the association of miR-126-3p, miR-126-5p and miR-664-3p tumour expression levels with outcomes of patients with metastatic colorectal cancer treated with bevacizumab. The study included 63 patients. For the assessment of microRNA expression, gene-specific TaqMan assays were used. The median progression-free survival and overall survival for patients with low tumour expression of miR-126-3p were 8.8 and 20.6 months versus 13.5 months and median overall survival was not reached for patients with high expression (p = 0.0064 and p = 0.0027), respectively. The median progression-free survival and overall survival for patients with low tumour expression of miR-126-5p were 9.0 and 22.2 months versus 12.0 and 23.4 months for patients with high expression (p = 0.2113 and 0.6858), respectively. The median progression-free survival and overall survival for patients with low tumour expression of miR-664-3p were 9.1 and 22.5 months versus 8.8 and 23.4 months for patients with high expression (p = 0.2542 and p = 0.1922), respectively. The multivariable Cox proportional hazards model revealed that miR-126-3p expression was significantly associated with progression-free survival (hazard ratio = 0.28, p = 0.0053) and also with overall survival (hazard ratio = 0.18, p = 0.0046). In conclusion, the results of this study suggest that the expression of miR-126-3p in the tumour tissue was associated with outcome of metastatic colorectal cancer patients treated with bevacizumab.

Morphological Characterization of Papillary Renal Cell Carcinoma Type 1, the Efficiency of Its Surgical Treatment.

Aim: Papillary renal cell carcinoma type 1 (pRCC1) represents the second most common type of malignant renal epithelial tumour. The origin of its characteristic appearance, its growth mechanism, and the long-term efficiency of its surgical treatment remain uncertain. Our aim was to determine typical characteristics of surgically treated pRCC1. Methods: pRCC1 was verified in 83 of 1,629 (5.1%) kidney tumours surgically treated in the period of January 2007-January 2016. The clinical and radiological characteristics, type of surgery, histopathology results and follow up data were recorded. Spearman correlation, Kruskal-Wallis analysis of variance, Fishers exact, and chi-square test were used to analyse appropriate variables. The overall survival rate was evaluated using the Gehan-Wilcoxon test and the Cox proportional hazards model. Results: The mean tumour size was 52.0 mm (15-180); 98.8% of the tumours showed a spherical shape and in 82.1%, exophytic growth was observed. Partial nephrectomy was performed in 80.7%. A majority (81.9%) were classified as pT1. Tumours, 89.2% of them, belonged to Fuhrman grade 1 or 2. The mean follow-up was 46.8 months. The overall survival was associated with pT category (p ≤ 0.0001). Conclusions: Typical signs of pRCC1 are a spherical shape, exophytic growth and low Fuhrmans grade. More than three-fourths of pRCC1 could be treated by the nephron-sparing surgery.

Introducing Support for Embedded and Real-Time Devices into Existing Hierarchical Component System: Lessons Learned

As embedded and real-time systems became an inherent part of many electronic appliances of everyday use, the demand for their development has grown enormously. Increasing complexity of these systems leads to demands of tools and techniques addressing their efficient and short time-to-market development. One of the possible ways to tackle the problem is a reuse of tools, methodologies and know how already established and successfully adopted in other application domains. Such transfer cannot be done inherently without appropriate modification and methodical adaptation based on an analysis of domain requirements. The paper analyzes necessary modifications and extensions of a general purpose component-based technology to enable development of embedded real-time systems. In addition, we present our own experience obtained while tailoring advanced component framework SOFA 2 to support development of embedded and real-time systems.

Cystic Appearance on Imaging Methods (Bosniak III-IV) in Histologically Confirmed Papillary Renal Cell Carcinoma is Mainly Characteristic of Papillary Renal Cell Carcinoma Type 1 and Might Predict a Relatively Indolent Behavior of Papillary Renal Cell Carcinoma

Aim: The aim of this study was to determine the proportion of cystic tumors according to preoperative CT (Bosniak III, IV) among surgically treated patients with histologically confirmed papillary renal cell carcinoma (pRCC) and to assess progression rates among patients with and without cystic appearance on imaging. Methods: A total of 138 patients with pRCC histology surgically treated in the period of January 2007–March 2017 were included. Clinical and radiological characteristics, type of surgery, histopathology results, and follow-up data were recorded and statistically evaluated. Results: Forty-one cases (29.7%) of cystic lesions (10× BIIF, 14× BIII, 17× BIV) were detected by CT. Patients with pRCC1 significantly more frequently presented with cystic appearance on CT (33/78; 42.3%) in comparison to other papillary types (8/60; 13.3%; p = 0.0002). During a median follow-up time of 49.4 months, only 2 patients with cystic lesions progressed after surgery. Conclusions: Cystic appearance on imaging methods is mainly a characteristic of pRCC1 (42.3%). Cystic morphology on imaging might predict a relatively indolent behavior of all pRCC types. Preoperative scoring systems including tumor growth patterns (cystic vs. solid) are needed for further classification.