Fuzzing is a software testing technique that finds bugs by repeatedly injecting mutated inputs to a target program. Known to be a highly practical approach, fuzzing is gaining more popularity than ever before. Current research on fuzzing has focused on producing an input that is more likely to trigger a vulnerability. In this paper, we tackle another way to improve the performance of fuzzing, which is to shorten the execution time of each iteration. We observe that AFL, a state-of-the-art fuzzer, slows down by 24× because of file system contention and the scalability of fork() system call when it runs on 120 cores in parallel. Other fuzzers are expected to suffer from the same scalability bottlenecks in that they follow a similar design pattern. To improve the fuzzing performance, we design and implement three new operating primitives specialized for fuzzing that solve these performance bottlenecks and achieve scalable performance on multi-core machines. Our experiment shows that the proposed primitives speed up AFL and LibFuzzer by 6.1 to 28.9× and 1.1 to 735.7×, respectively, on the overall number of executions per second when targeting Google's fuzzer test suite with 120 cores. In addition, the primitives improve AFL's throughput up to 7.7× with 30 cores, which is a more common setting in data centers. Our fuzzer-agnostic primitives can be easily applied to any fuzzer with fundamental performance improvement and directly benefit large-scale fuzzing and cloud-based fuzzing services. CCS CONCEPTS • Security and privacy → Vulnerability scanners; • Software and its engineering → Software testing and debugging;

Regulation of atrial release of atrial natriuretic peptide (ANP) is coupled to changes in atrial dynamics. However, the mechanism by which mechanical stretch controls myocytic ANP release must be defined. The purpose of this study was to define the mechanism by which cAMP controls myocytic ANP release in perfused, beating rabbit atria. The cAMP-elevating agents forskolin and 3-isobutyl-1-methylxanthine (IBMX) inhibited myocytic ANP release. The activation of adenylyl cyclase with forskolin inhibited ANP release, which was a function of an increase in cAMP production. Inhibitors for L-type Ca 2ϩ channels and protein kinase A (PKA) attenuated a minor portion of the forskolin-induced inhibition of ANP release. Gö-6976 and KN-62, which are specific inhibitors for protein kinase C-␣ and Ca 2ϩ /calmodulin kinase, respectively, failed to modulate forskolin-induced inhibition of ANP release. The nonspecific protein kinase inhibitor staurosporine blocked forskolin-induced inhibition of ANP release in a dose-dependent manner. Staurosporine but not nifedipine shifted the relationship between cAMP and ANP release. Inhibitors for Ltype Ca 2ϩ channels and PKA and staurosporine blocked forskolin-induced accentuation of atrial dynamics. These results suggest that cAMP inhibits atrial myocytic release of ANP via protein kinase-dependent and L-type Ca 2ϩ -channeldependent and -independent signaling pathways. atrial natriuretic peptide; forskolin; phosphodiesterase; channels ENDOCRINE ATRIUM SYNTHESIZES and releases a family of natriuretic peptides including atrial natriuretic peptide (ANP) and brain natriuretic peptide (7,19). C-type natriuretic peptide, a third member of the natriuretic peptide family (32) that is synthesized in the atrium, may have paracrine/autocrine function for the regulation of ANP release (17).There have been reports on the variable modulators for the control of ANP release (23). However, the specific control mechanism for ANP release must be defined. The most prominent activator for atrial secretion of ANP has been shown to be the stretch and/or release of atrial wall (2, 10, 16). However, the intracellular mechanism responsible for the activation of ANP release by mechanical stimulation is unknown.The potential roles of cyclic nucleotides and Ca 2ϩ in the regulation of ANP release have been subjects of interest. Recently we found that both cGMP and Ca 2ϩ are negative regulators for atrial myocytic release of ANP (4, 14, 17). There are diverse reports on the effects of cAMP in the regulation of ANP secretion. Forskolin, an activator of adenylyl cyclase (AC), has been shown to decrease ANP release from cultured atrial myocytes (12,20,30) and perfused rat heart (25); 3-isobutyl-1-methylxanthine (IBMX), a nonselective inhibitor of cyclic nucleotide phosphodiesterase (PDE) (12), and 8-bromoadenosine 3Ј,5Ј-cyclic monophosphate (8-BrcAMP) (12, 30), have also been shown to inhibit ANP secretion. In contrast, it has also been shown that cAMP-elevating agents (1,5,24) and cell membranepermeant cAMP analogs (1,5,27...

File systems, a basic building block of an OS, are too big and too complex to be bug free. Nevertheless, file systems rely on regular stress-testing tools and formal checkers to find bugs, which are limited due to the ever-increasing complexity of both file systems and OSes. Thus, fuzzing, proven to be an effective and a practical approach, becomes a preferable choice, as it does not need much knowledge about a target. However, three main challenges exist in fuzzing file systems: mutating a large image blob that degrades overall performance, generating image-dependent file operations, and reproducing found bugs, which is difficult for existing OS fuzzers.Hence, we present JANUS, the first feedback-driven fuzzer that explores the two-dimensional input space of a file system, i.e., mutating metadata on a large image, while emitting imagedirected file operations. In addition, JANUS relies on a library OS rather than on traditional VMs for fuzzing, which enables JANUS to load a fresh copy of the OS, thereby leading to better reproducibility of bugs. We evaluate JANUS on eight file systems and found 90 bugs in the upstream Linux kernel, 62 of which have been acknowledged. Forty-three bugs have been fixed with 32 CVEs assigned. In addition, JANUS achieves higher code coverage on all the file systems after fuzzing 12 hours, when compared with the state-of-the-art fuzzer Syzkaller for fuzzing file systems. JANUS visits 4.19× and 2.01× more code paths in Btrfs and ext4, respectively. Moreover, JANUS is able to reproduce 88-100% of the crashes, while Syzkaller fails on all of them.

Interstitial cells of Cajal (ICCs) are the pacemaking cells in the gastrointestinal muscles that generate the rhythmic oscillations in membrane potential known as slow waves. ICCs also mediate or transduce inputs from the enteric nervous system. Substance P (SubP) is a member of the family of mammalian tachykinin peptides that are predominantly released by enteric neurons. This study assessed the relationship of Na⁺-leak channel (NALCN) in the SubP-induced depolarization in pacemaking activity in the gastrointestinal tract. The patch-clamp technique for whole-cell recording was used in cultured cluster and single ICCs. Electrophysiological and pharmacological properties of SubP in ICC pacemaking activity were similar to those of NALCN. Reverse-transcription polymerase chain reaction, Western blotting, and immunohistochemistry all showed abundant and localized expression of NALCN messenger RNA and protein in mouse small intestine. NALCN is involved in the SubP-induced depolarization of intestinal pacemaking activity. The protein is a potential target for pharmacological treatment of motor disorders of the gut.

The effect of membrane stretch on voltage-activated Ba2+ current (IBa) was studied in antral circular myocytes of guinea-pig using the whole- cell patch-clamp technique. The changes in cell volume were elicited by superfusing the myocytes with anisosmotic solutions. Hyposmotic superfusate (202 mosmol/l) induced cell swelling and increased peak values of IBa at 0 mV (from -406.6 +/- 45.5 pA to -547.5 +/- 65.6 pA, mean +/- SEM, n = 8) and hyperosmotic superfusate (350 mosmol/l) induced cell shrinkage and decreased peak values of IBa at 0 mV (to -269.5 +/- 39.1 pA, n = 8). Such changes were reversible and the extent of change was dependent on the osmolarity of superfusate. The values of normalized IBa at 0 mV were 1.43 +/- 0.04, 1.30 +/- 0.06, 1.23 +/- 0.04, 1.19 +/- 0.04, 1 and 0. 68 +/- 0.06 at 202, 220, 245, 267, 290 and 350 mosmol/l, respectively (n = 8). IBa was almost completely blocked by nicardipine (5 microM) under hyposmotic conditions. The values of steady-state half-inactivation voltage (-37.7 +/- 3.3 and -36.5 +/- 2.6 mV, under control and hyposmotic conditions, respectively) or the half-activation voltage (-13.6 +/- 2.3 and -13.9 +/- 1.9 mV) of IBa were not significantly changed (P > 0.05, n = 6). Cell membrane capacitance was slightly increased from 50.00 +/- 2.86 pF to 50.22 +/- 2.82 pF by a hyposmotic superfusate (P < 0.05, n = 6). It is suggested that cell swelling increases voltage-operated L-type calcium channel current and that such a property is related to the response of gastric smooth muscle to mechanical stimuli.