Understanding Large Language Model Based Fuzz Driver Generation

Fuzz drivers are a necessary component of API fuzzing. However, automatically generating correct and robust fuzz drivers is a difficult task. Compared to existing approaches, LLM-based (Large Language Model) generation is a promising direction due to its ability to operate with low requirements on consumer programs, leverage multiple dimensions of API usage information, and generate human-friendly output code. Nonetheless, the challenges and effectiveness of LLM-based fuzz driver generation remain unclear. To address this, we conducted a study on the effects, challenges, and techniques of LLM-based fuzz driver generation. Our study involved building a quiz with 86 fuzz driver generation questions from 30 popular C projects, constructing precise effectiveness validation criteria for each question, and developing a framework for semi-automated evaluation. We designed five query strategies, evaluated 36,506 generated fuzz drivers. Furthermore, the drivers were compared with manually written ones to obtain practical insights. Our evaluation revealed that: while the overall performance was promising (passing 91% of questions), there were still practical challenges in filtering out the ineffective fuzz drivers for large scale application; basic strategies achieved a decent correctness rate (53%), but struggled with complex API-specific usage questions. In such cases, example code snippets and iterative queries proved helpful; while LLM-generated drivers showed competent fuzzing outcomes compared to manually written ones, there was still significant room for improvement, such as incorporating semantic oracles for logical bugs detection.Comment: 17 pages, 14 figure

The single-cell landscape of cystic echinococcosis in different stages provided insights into endothelial and immune cell heterogeneity

IntroductionHydatid cysts and angiogenesis are the key characteristics of cystic echinococcosis, with immune cells and endothelial cells mediating essential roles in disease progression. Recent single-cell analysis studies demonstrated immune cell infiltration after Echinococcus granulosus infection, highlighting the diagnostic and therapeutic potential of targeting certain cell types in the lesion microenvironment. However, more detailed immune mechanisms during different periods of E. granulosus infection were not elucidated.MethodsHerein, we characterized immune and endothelial cells from the liver samples of mice in different stages by single-cell RNA sequencing.ResultsWe profiled the transcriptomes of 45,199 cells from the liver samples of mice at 1, 3, and 6 months after infection (two replicates) and uninfected wild-type mice. The cells were categorized into 26 clusters with four distinct cell types: natural killer (NK)/T cells, B cells, myeloid cells, and endothelial cells. An SPP1+ macrophage subset with immunosuppressive and pro-angiogenic functions was identified in the late infection stage. Single-cell regulatory network inference and clustering (SCENIC) analysis suggested that Cebpe, Runx3, and Rora were the key regulators of the SPP1+ macrophages. Cell communication analysis revealed that the SPP1+ macrophages interacted with endothelial cells and had pro-angiogenic functions. There was an obvious communicative relationship between SPP1+ macrophages and endothelial cells via Vegfa–Vegfr1/Vegfr2, and SPP1+ macrophages interacted with other immune cells via specific ligand–receptor pairs, which might have contributed to their immunosuppressive function.DiscussionOur comprehensive exploration of the cystic echinococcosis ecosystem and the first discovery of SPP1+ macrophages with infection period specificity provide deeper insights into angiogenesis and the immune evasion mechanisms associated with later stages of infection

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

A method for de novo nucleic acid diagnostic target discovery

Motivation: A proper target or marker is essential in any diagnosis (e.g. an infection or cancer). An ideal diagnostic target should be both conserved in and unique to the pathogen. Currently, these targets can only be identified manually, which is time-consuming and usually error-prone. Because of the increasingly frequent occurrences of emerging epidemics and multidrug-resistant \u27superbugs\u27, a rapid diagnostic target identification process is needed

A FASTQ compressor based on integer-mapped k-mer indexing for biologist

Next generation sequencing (NGS) technologies have gained considerable popularity among biologists. For example, RNA-seq, which provides both genomic and functional information, has been widely used by recent functional and evolutionary studies, especially in non-model organisms. However, storing and transmitting these large data sets (primarily in FASTQ format) have become genuine challenges, especially for biologists with little informatics experience. Data compression is thus a necessity. KIC, a FASTQ compressor based on a new integer-mapped k-mer indexing method, was developed (available at http://www.ysunlab.org/kic.jsp). It offers high compression ratio on sequence data, outstanding user-friendliness with graphic user interfaces, and proven reliability. Evaluated on multiple large RNA-seq data sets from both human and plants, it was found that the compression ratio of KIC had exceeded all major generic compressors, and was comparable to those of the latest dedicated compressors. KIC enables researchers with minimal informatics training to take advantage of the latest sequence compression technologies, easily manage large FASTQ data sets, and reduce storage and transmission cost

Elucidating Escherichia Coli O157:H7 Colonization and Internalization in Cucumbers Using an Inverted Fluorescence Microscope and Hyperspectral Microscopy

Contamination of fresh cucumbers (Cucumis sativus L.) with Escherichia coli O157:H7 can impact the health of consumers. Despite this, the pertinent mechanisms underlying E. coli O157:H7 colonization and internalization remain poorly documented. Herein we aimed to elucidate these mechanisms in cucumbers using an inverted fluorescence microscope and hyperspectral microscopy. We observed that E. coli O157:H7 primarily colonized around the stomata on cucumber epidermis without invading the internal tissues of intact cucumbers. Once the bacterial cells had infiltrated into the internal tissues, they colonized the cucumber placenta and vascular bundles (xylem vessels, in particular), and also migrated along the xylem vessels. Moreover, the movement rate of E. coli O157:H7 from the stalk to the flower bud was faster than that from the flower bud to the stalk. We then used hyperspectral microscope imaging to categorize the infiltrated and uninfiltrated areas with high accuracy using the spectral angle mapper (SAM) classification method, which confirmed the results obtained upon using the inverted fluorescence microscope. We believe that our results are pivotal for developing science-based food safety practices, interventions for controlling E. coli O157:H7 internalization, and new methods for detecting E. coli O157:H7-plant interactions

Electroacupuncture Ameliorates Cerebral I/R-Induced Inflammation through DOR-BDNF/TrkB Pathway

The beneficial effects of electroacupuncture (EA) at Shuigou (GV26) and Neiguan (PC6) on poststroke rehabilitation are critically related to the activation of the delta-opioid receptor (DOR). The underlying anti-inflammatory mechanisms in DOR activation and EA-mediated neuroprotection in cerebral ischemia/reperfusion (I/R) injury were investigated in the current study. Cell proliferation and apoptosis were detected by morphological changes, cell counting kit-8 (CCK-8) assay, lactate dehydrogenase (LDH) release, and TUNEL staining. The mRNA levels were evaluated by using real-time quantitative polymerase chain reaction (RT-qPCR), and the protein expression was measured by western blot or enzyme-linked immunosorbent assay (ELISA) in vitro. Infarct volume was examined by cresyl violet (CV) staining, neurologic recovery was assessed by neurological deficit scores, and pro- and anti-inflammatory cytokines were determined by immunofluorescence in vivo. DOR activation greatly ameliorated morphological injury, reduced LDH leakage and apoptosis, and increased cell viability. It reversed the oxygen-glucose deprivation/reoxygenation- (OGD/R-) induced downregulation of DOR mRNA and protein, as well as BDNF protein. DOR activation also reduced proinflammatory cytokine gene expression, including TNF-α, IL-1β, and IL-6, and at the same time, increased anti-inflammatory cytokines IL-4 and IL-10 in OGD/R challenged PC12 cells. EA significantly reduced middle cerebral artery occlusion/reperfusion- (MCAO/R-) induced infarct volume and attenuated neurologic deficit scores. It markedly increased the expression of IL-10 and decreased IL-1β, while sham EA did not have any protective effect in MCAO/R-injured rats. DOR activation plays an important role in neuroprotection against OGD/R injury by inhibiting inflammation via the brain-derived neurotrophic factor/tropomyosin-related kinase B (BDNF/TrkB) pathway. The neuroprotective efficacy of EA at Shuigou (GV26) and Neiguan (PC6) on cerebral I/R injury may be also related to the inhibition of inflammatory response through the DOR-BDNF/TrkB pathway

Investigation on the Microbial Diversity of Fresh-Cut Lettuce during Processing and Storage Using High Throughput Sequencing and Their Relationship with Quality

Microbial community distribution in vegetables can affect their quality. This study analyzed the distribution of the microbial community at various stages during processing and storage with the microbial diversity analysis, and evaluated the correlation between the dominant bacteria and sensory quality of lettuce using correspondence analysis with multiple regression analysis. Results showed that the process of washing, cutting, then disinfection and dewatering could change the community distribution and dominant bacteria in lettuce, and maintain better texture, morphology, aroma, color qualities of lettuce. The total number of colonies and relative abundance of Xanthomonas in fresh-cut lettuce decreased, while Afipia and Ralstonia increased during processing and pre-storage (storage for 6 h, 12 h and 1 d). After storage for 3 d, the total number of colonies in lettuce increased (more than 5 log CFU/g), especially the relative abundance of Pseudomonas, which led to the obvious deterioration of the sensory quality of lettuce. Throughout the process, the number of Bacillus cereus, Staphylococcus aureus, and E. coli was less than 100 CFU/g and 3 MPN/g. The number of typical pathogenic bacteria, Salmonella, Listeria monocytogenes and E. coli O157:H7, was below the detection limit. Overall, the prevention and control of psychrotrophic Pseudomonas in lettuce was still necessary. These results will provide useful information for the fresh-cut lettuce industry

Physical and electrochemical behaviors of AgX (X = S/I) in a GeS2–Sb2S3 chalcogenide-glass matrix

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