This paper presents a framework for evaluating the transport layer feature space of malware heartbeat traffic. We utilize these features in a prototype detection system to distinguish malware traffic ...from traffic generated by legitimate applications. In contrast to previous work, we eliminate features at risk of producing overly optimistic detection results, detect previously unobserved anomalous behavior, and rely only on tamper-resistant features making it difficult for sophisticated malware to avoid detection. Further, we characterize the evolution of malware evasion techniques over time by examining the behavior of 16 malware families. In particular, we highlight the difficultly of detecting malware that use traffic-shaping techniques to mimic legitimate traffic.
Experimentation is critical to understanding the malware operation and to evaluating potential defenses. However, constructing the controlled environments needed for this experimentation is both ...time-consuming and error-prone. In this study, we highlight several common mistakes made by researchers and conclude that existing evaluations of malware detection techniques often lack in both flexibility and transparency. For instance, we show that small variations in the malware’s behavioral parameters can have a significant impact on the evaluation results. These variations, if unexplored, may lead to overly optimistic conclusions and detection systems that are ineffective in practice. To overcome these issues, we propose a framework to model malware behavior and guide systematic parameter selection. We evaluate our framework using a synthetic botnet executed within the CyberVAN testbed. Our study is intended to foster critical evaluation of proposed detection techniques and stymie unintentionally erroneous experimentation.
: Users trust IoT apps to control and automate their smart devices. These apps necessarily have access to sensitive data to implement their functionality. However, users lack visibility into how ...their sensitive data is used, and often blindly trust the app developers. In this paper, we present IoTWATcH, a dynamic analysis tool that uncovers the privacy risks of IoT apps in real-time. We have designed and built IoTWATcH through a comprehensive IoT privacy survey addressing the privacy needs of users. IoTWATCH operates in four phases: (a) it provides users with an interface to specify their privacy preferences at app install time, (b) it adds extra logic to an app’s source code to collect both IoT data and their recipients at runtime, (c) it uses Natural Language Processing (NLP) techniques to construct a model that classifies IoT app data into intuitive privacy labels, and (d) it informs the users when their preferences do not match the privacy labels, exposing sensitive data leaks to users. We implemented and evaluated IoTWATcH on real IoT applications. Specifically, we analyzed 540 IoT apps to train the NLP model and evaluate its effectiveness. IoTWATcH yields an average 94.25% accuracy in classifying IoT app data into privacy labels with only 105 ms additional latency to an app’s execution.
The genes for axin inhibition protein 2 (AXIN2), msh homeobox 1 (MSX1), and paired box gene 9 (PAX9) are involved in tooth root formation and tooth development. Mutations of the AXIN2, MSX1, and PAX9 ...genes are associated with non-syndromic oligodontia. In this study, we investigated phenotype and AXIN2, MSX1, and PAX9 gene variations in two Mexican families with non-syndromic oligodontia. Individuals from two families underwent clinical examinations, including an intra-oral examination and panoramic radiograph. Retrospective data were reviewed, and peripheral blood samples were collected. The exons and exon-intronic boundaries of the AXIN2, MSX1, and PAX9 genes were sequenced and analyzed. Protein and messenger RNA structures were predicted using bioinformative software programs. Clinical and oral examinations revealed isolated non-syndromic oligodontia in the two Mexican families. The average number of missing teeth was 12. The sequence analysis of exons and exon-intronic regions of AXIN2, MSX1, and PAX9 revealed 11 single-nucleotide polymorphisms (SNPs), including seven in AXIN2, two in MSX1, and three in PAX9. One novel SNP of MSX1, c.476T>G (Leu159Arg), was found in all of the studied patients in the families. MSX1 Leu159Arg and PAX9 Ala240Pro change protein and messenger RNA structures. Our findings suggested that a combined reduction of MSX1 and PAX9 gene dosages increased the risk for oligodontia in the Mexican families, as in vivo investigation has indicated that interaction between Msx1 and Pax9 is required for tooth development.
Recognition that soil resources are fragile has increased interest in soil health promoting practices (SHPPs) and ways to monitor changes in agricultural soil health. To enhance this effort, ...inexpensive and user-friendly methods are needed. Especially methods to measure biological activity, which is central to soil health but current methods are expensive and inconvenient. Our objective was to quantify biological activity by monitoring decomposition (via mass loss) of common household items green and rooibos tea (Camellia sinensis and Aspalathus linearis), bleached cotton (Gossypium hirsutum), and birch craft sticks (Betula spp.), and compare these results with common laboratory measurements of biological soil health (microbial biomass carbon and nitrogen, permanganate oxidizable carbon, and potentially mineralizable carbon and nitrogen). First, we compared both strategies using correlation, including with the yield of the dominant crop in the region maize (Zea mays L.). Second, we evaluated their response to several long-term SHPPs: (i) biochar, (ii) winter cover crops, (iii) nitrogen fertilizer, (iv) no-tillage, (v) diversified rotation, (vi) perennial crops, (vii) crop residue addition/removal, and (viii) prairie restoration. Correlations between decomposition and laboratory measurements were poor and often negative. Maize yield positively correlated with tea decomposition but not with the laboratory indicators. Based on ‘signal-to-noise’ ratios, or magnitude of SHPP treatment effect compared to variability, measurements of decomposition, especially mass loss of rooibos tea (for 4 days) and bleached cotton (for 35 days), outperformed many of the laboratory indicators in detecting treatment differences. Decomposition was also easier and less expensive than laboratory methods indicating it is a simple, yet scientifically defensible, alternative for measuring soil biological health in agroecosystems.
•Laboratory soil health indicators were compared to decomposition of household items.•Decomposition of tea positively correlated with maize yield, laboratory indicators did not.•Rooibos tea decomposition had greater signal-to-noise than laboratory indicators.•Bleached cotton decomposition was variable, but showed large treatment effects.•Household item decomposition is an accessible alternative to laboratory indicators.
IntroductionTumour development begins with mutational changes to the genetic makeup of a cell; tumour progression is not solely determined by the mutated cell, but also by the tumour’s ...microenvironment. Prostate cancer, a leading cancer diagnosed in men, has been determined to be highly influenced by its surrounding stroma, particularly fibroblasts. It has been demonstrated that cancer-associated prostate fibroblasts (CAFs) differ from normal-associated prostate fibroblasts (NAFs). However, human prostate cancer model systems have focused largely on prostate cancer epithelial cells. Currently, a need exists for a more physiologically relevant human cell model system to study prostate cancer progression within the context of its tumour microenvironment.Material and methodsIn this study, we characterised three prostate-derived cells: CAFs, NAFs, and prostate epithelial cells (PrEs); all three lines were immortalised by human telomerase reverse transcriptase (hTERT) alone and selected with puromycin. The selected clones grew continuously in culture for more than 40 population doublings in our hands.Results and discussionsOur data shows that the hTERT-immortalised CAFs proliferate faster than the NAFs; in addition, both CAFs and NAFs express fibroblast markers such as TE7 and alpha smooth muscle actin (a-SMA), while neither cell line expresses epithelial markers such as CK14. Both CAFs and NAFs also express elevated levels of a-SMA upon TGF-b stimulation. All three prostate-derived cells weakly express the prostate specific marker AR, and show similar markers staining after long time passaging. Importantly, conditioned media collected from CAFs promotes tumour cell growth better than NAF conditioned media.ConclusionIn conclusion, CAFs, NAFs, and immortalised PrEs may provide a very valuable model system for the study of prostate cancer cell progression and tumour microenvironment studies.
Selectins and their carbohydrate ligands mediate the homing of hematopoietic stem/progenitor cells (HSPCs) to the bone marrow. We have previously shown that ex vivo fucosylation of selectin ligands ...on HSPCs by α1,3 fucosyltransferase VI (FUT6) leads to improved human cord blood (CB)-HSPC engraftment in non-obese diabetic (NOD)/severe combined immune deficient (SCID) mice. In the present study, we determined whether surface fucosylation with α1,3 fucosyltransferase VII (FUT7), which is primarily expressed by hematopoietic cells, improves the function of selectin ligands on CB-HSPCs in comparison with FUT6. A saturating amount of either FUT6 or FUT7, which generates comparable levels of expression of fucosylated epitopes on CB CD34(+) cells, was used for these experiments. In vitro, FUT7-treated CB CD34(+) cells exhibited greater binding to P- or E-selectin than that of FUT6-treated CB CD34(+) cells under static or physiological flow conditions. In vivo, FUT7 treatment, like FUT6, improved the early engraftment of CB CD34(+) cells in the bone marrow of sublethally irradiated NOD/SCID interleukin (IL)-2Rγ(null) (NSG) mice. FUT7 also exhibited marginally-yet statistically significant-increased engraftment at 4 and 6 weeks after transplantation. In addition, FUT7-treated CB CD34(+) cells exhibited increased homing to the bone marrow of irradiated NSG mice relative to sham-treated cells. These data indicate that FUT7 is effective at improving the function of selectin ligands on CB-HSPCs in vitro and enhancing early engraftment of treated CB-HSPCs in the bone marrow of recipients.
Although viral infection is preventable by vaccination and antiviral treatments are available, up to 1 million people die every year from hepatitis B virus (HBV)-associated liver diseases. In line ...with this notion, there is an effective vaccine available for feline leukemia virus (FeLV), but FeLV remains a common infection among domesticated cat populations and accounts for many clinical syndromes that typically end with death within 1 to 3 years after the initial diagnosis. Therefore, the need for new antiviral agents for treating human and veterinary viral pathogens exists, even in instances where effective vaccines are available. Reverse transcriptase (RT) is an essential enzyme for the replication life cycle of both retroviruses (i.e., human immunodeficiency virus type 1, HIV-1) and hepadnaviruses (i.e., HBV). Previous studies have shown two types of small molecules possessing anti-HIV-1 activity, mainly through targeting reverse transcriptase (RT) and the reverse transcription pathway - namely viral mutagens (i.e., decitabine, 5-azacytidine and KP1212) and ribonucleotide reductase inhibitors (RNRIs) (i.e., gemcitabine and resveratrol). Our research group has shown that decitabine and gemcitabine can also inhibit FeLV and murine leukemia viruses (MuLV) replication, which are closely related gammaretroviruses.Based upon these observations, Part 1 of this dissertation sought to test following two hypotheses: 1) mutagen and RNRI or the combination of a mutagen and an RNRI will possess potent anti-HBV activity; and 2) distinct antiviral mechanisms can be elicited by a viral mutagen. A family of host proteins, i.e., human apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 (APOBEC3, A3) proteins, can induce viral mutagenesis, and therefore act as a cellular-based viral mutagen. APOBEC3 family member proteins can deaminate cytosines in single-strand (ss) DNA, which restricts HIV-1, retrotransposons, and other viruses such as HBV, but can cause a mutator phenotype in many cancers. Part 2 of this dissertation sought to characterize the deamination hotspots of APOBEC3 proteins, and to test the hypothesis that deamination hotspots among APOBEC3 family members are defined by both target site sequence and ssDNA structure. Although anti-HBV therapeutic discovery targeting host factors and screening for inhibitors are in progress, there is a significant knowledge gap regarding HBV-host cell interaction. This line of research investigation is critical to public health as HBV infection accounts for 54% of all hepatocellular carcinomas (HCCs), which is notable as it is the second highest cause of cancer-related mortality worldwide. An enhanced understanding of HBV-host cell interactions will help to improve general knowledge of HBV biology, identify potential targets for antiviral intervention to prevent HCC, and provide insights that could prove useful in the early diagnosis of HCC and the discovery of HCC-targeted therapeutics. Part 3 of this dissertation describes the results of an analysis of HBV-infected cells for testing the hypothesis that host genes involved in the cellular antiviral response and HCC development can be identified by transcriptome analysis. Together, the studies conducted in this dissertation serve to lay the foundation for future basic and translational research studies.
Background While eating disorders (EDs) are thought to result from a combination of environmental and psychological stressors superimposed upon genetic vulnerability; the neurobiological basis of EDs ...remains incompletely understood. We recently reported that a rare missense mutation in the gene for the transcriptional repressor histone deacetylase 4 ( HDAC4 ) is associated with the risk of developing an ED in humans. Methods To understand the biological consequences of this missense mutation, we created transgenic mice carrying this mutation by introducing the alanine to threonine mutation at position 778 of mouse HDAC4 (corresponding to position 786 of the human protein). Bioinformatic analysis to identify HDAC4-regulated genes was performed using available databases. Results Male mice heterozygous for HDAC4A778T did not show any metabolic or behavioral differences. In contrast, female mice heterozygous for HDAC4A778T display several ED-related feeding and behavioral deficits depending on housing condition. Individually-housed HDAC4A778T female mice exhibit reduced effortful responding for high-fat diet and compulsive grooming, while group-housed female mice display increased weight gain on high-fat diet, reduced behavioral despair and increased anxiety-like behaviors. Bioinformatic analysis identifies mitochondrial biogenesis including synthesis of glutamate/GABA as a potential transcriptional target of HDAC4A778T activity relevant to the behavioral deficits identified in this new mouse model of disordered eating. Conclusions The HDAC4A778T mouse line is a novel model of ED-related behaviors and identifies mitochondrial biogenesis as a potential molecular pathway contributing to behavioral deficits.
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