Search Results (4)

Design-for-test/debug (DfT/D) introduces scan chain testing to increase testability and fault coverage by inserting scan flip-flops. However, these scan chains are also known to be a liability for security primitives. In previous research, the dynamically obfuscated scan chain (DOSC) was introduced to protect logic-locking keys from scan-based attacks by obscuring test patterns and responses. In this paper, we present DOSCrack, an oracle-guided attack to de-obfuscate DOSC using symbolic execution and binary clustering, which significantly reduces the candidate seed space to a manageable quantity. Our symbolic execution engine employs scan mode simulation and satisfiability modulo theories (SMT) solvers to reduce the possible seed space, while obfuscation key clustering allows us to effectively rule out a group of seeds that share similarities. An integral component of our approach is the use of sequential equivalence checking (SEC), which aids in identifying distinct simulation patterns to differentiate between potential obfuscation keys. We experimentally applied our DOSCrack framework on four different sizes of DOSC benchmarks and compared their runtime and complexity. Finally, we propose a low-cost countermeasure to DOSCrack which incorporates a nonlinear feedback shift register (NLFSR) to increase the effort of symbolic execution modeling and serves as an effective defense against our DOSCrack framework. Our research effectively addresses a critical vulnerability in scan-chain obfuscation methodologies, offering insights into DfT/D and logic locking for both academic research and industrial applications. Our framework highlights the need to craft robust and adaptable defense mechanisms to counter evolving scan-based attacks. Full article

Background: Serous endometrial carcinoma (SEC) is a high-risk subtype of endometrial cancer. The effectiveness of multiple adjuvant therapies, namely chemotherapy (CT), radiotherapy (RT), and sequential/concurrent chemotherapy with radiotherapy (CRT), have previously been investigated. However, optimal management of early-stage SEC remains unclarified. Methods: All cases of early-stage SEC (FIGO 2009 stages I–II) treated in our institution from 2002 to 2019 were identified. Patient data were documented until September 2023. Overall survival (OS) and disease-free survival (DFS) were computed using Kaplan–Meier estimates and Cox’s proportional hazard model; descriptive statistical analysis was performed. Results: A total of 50 patients underwent total hysterectomy-bilateral salpingo-oophorectomy and omentectomy, displaying stage IA (60%), IB (24%), and II (16%) disease. The median follow-up was 90.9 months. Patients underwent adjuvant CRT (n = 36, 72%), CT (n = 6, 12%), or RT (n = 6, 12%). Two patients were observed and excluded from analyses. The 42 patients who received radiotherapy had pelvic external beam radiotherapy (n = 10), vaginal brachytherapy (n = 21), or both (n = 11). CRT had better OS (HR 0.14, 95%CI 0.04–0.52, p < 0.005) and DFS (HR 0.25, 95%CI 0.07–0.97, p = 0.05) than CT alone. RT displayed no OS or DFS benefits compared to CT/CRT. Recurrences were mostly distant. Acute and late G3-4 toxicities were primarily hematologic. Conclusions: Our data underline the challenge of treating SEC. CRT appears to be superior to CT alone but not to RT. Most recurrences were distant, highlighting the need for optimized systemic treatment options. Full article

SecA is a widely conserved ATPase that drives the secretion of proteins across the cell membrane via the SecYEG translocon, while the SRP system is a key player in the insertion of membrane proteins via SecYEG. How SecA gains access to substrate proteins in Bacillus subtilis cells and copes with an increase in substrate availability during biotechnologically desired, high-level expression of secreted proteins is poorly understood. Using single molecule tracking, we found that SecA localization closely mimics that of ribosomes, and its molecule dynamics change similarly to those of ribosomes after inhibition of transcription or translation. These data suggest that B. subtilis SecA associates with signal peptides as they are synthesized at the ribosome, similar to the SRP system. In agreement with this, SecA is a largely mobile cytosolic protein; only a subset is statically associated with the cell membrane, i.e., likely with the Sec translocon. SecA dynamics were considerably different during the late exponential, transition, and stationary growth phases, revealing that single molecule dynamics considerably alter during different genetic programs in cells. During overproduction of a secretory protein, AmyE, SecA showed the strongest changes during the transition phase, i.e., where general protein secretion is high. To investigate whether the overproduction of AmyE also has an influence on other proteins that interact with SecYEG, we analyzed the dynamics of SecDF, YidC, and FtsY with and without AmyE overproduction. SecDF and YidC did not reveal considerable differences in single molecule dynamics during overexpression, while the SRP component FtsY changed markedly in its behavior and became more statically engaged. These findings indicate that the SRP pathway becomes involved in protein secretion upon an overload of proteins carrying a signal sequence. Thus, our data reveal high plasticity of the SecA and SRP systems in dealing with different needs for protein secretion. Full article

The translocation of specific polypeptide chains across membranes is an essential activity for all life forms. The main components of the general secretory (Sec) system of E. coli include integral membrane translocon SecYEG, peripheral ATPase SecA, and SecDF, an ancillary complex that enhances polypeptide secretion by coupling translocation to proton motive force. Atomic force microscopy (AFM), a single-molecule imaging technique, is well suited to unmask complex, asynchronous molecular activities of membrane-associated proteins including those comprising the Sec apparatus. Using AFM, the dynamic structure of membrane-external protein topography of Sec system components can be directly visualized with high spatial-temporal precision. This mini-review is focused on AFM imaging of the Sec system in near-native fluid conditions where activity can be maintained and biochemically verified. Angstrom-scale conformational changes of SecYEG are reported on 100 ms timescales in fluid lipid bilayers. The association of SecA with SecYEG, forming membrane-bound SecYEG/SecA translocases, is directly visualized. Recent work showing topographical aspects of the translocation process that vary with precursor species is also discussed. The data suggests that the Sec system does not employ a single translocation mechanism. We posit that differences in the spatial frequency distribution of hydrophobic content within precursor sequences may be a determining factor in mechanism selection. Precise AFM investigations of active translocases are poised to advance our currently vague understanding of the complicated macromolecular movements underlying protein export across membranes. Full article