Graph-tree-based software control flow checking for COTS processors on pico-satellites

AbstractThis paper proposes a generic high-performance and low-time-overhead software control flow checking solution, graph-tree-based control flow checking (GTCFC) for space-borne commercial-off-the-shelf (COTS) processors. A graph tree data structure with a topology similar to common trees is introduced to transform the control flow graphs of target programs. This together with design of IDs and signatures of its vertices and edges allows for an easy check of legality of actual branching during target program execution. As a result, the algorithm not only is capable of detecting all single and multiple branching errors with low latency and time overheads along with a linear-complexity space overhead, but also remains generic among arbitrary instruction sets and independent of any specific hardware. Tests of the algorithm using a COTS-processor-based on-board computer (OBC) of in-service ZDPS-1A pico-satellite products show that GTCFC can detect over 90% of the randomly injected and all-pattern-covering branching errors for different types of target programs, with performance and overheads consistent with the theoretical analysis; and beats well-established preeminent control flow checking algorithms in these dimensions. Furthermore, it is validated that GTCGC not only can be accommodated in pico-satellites conveniently with still sufficient system margins left, but also has the ability to minimize the risk of control flow errors being undetected in their space missions. Therefore, due to its effectiveness, efficiency, and compatibility, the GTCFC solution is ready for applications on COTS processors on pico-satellites in their real space missions

Unique caudal plumage of Jeholornis and complex tail evolution in early birds

The Early Cretaceous bird Jeholornis was previously only known to have a distally restricted ornamental frond of tail feathers. We describe a previously unrecognized fan-shaped tract of feathers situated dorsal to the proximal caudal vertebrae. The position and morphology of these feathers is reminiscent of the specialized upper tail coverts observed in males of some sexually dimorphic neornithines. As in the neornithine tail, the unique “two-tail” plumage in Jeholornis probably evolved as the result of complex interactions between natural and sexual selective pressures and served both aerodynamic and ornamental functions. We suggest that the proximal fan would have helped to streamline the body and reduce drag whereas the distal frond was primarily ornamental. Jeholornis reveals that tail evolution was complex and not a simple progression from frond to fan.Fil: O'Connor, Jingmai. Chinese Academy Of Sciences. Institute of Vertebrate Paleontology and Paleoanthropology; República de ChinaFil: Wang, Xiaoli. Linyi University; ChinaFil: Sullivan, Corwin. Chinese Academy Of Sciences. Institute of Vertebrate Paleontology and Paleoanthropology; República de ChinaFil: Zheng, Xiaoting. Linyi University; China. Shandong Tianyu Museum of Nature; ChinaFil: Tubaro, Pablo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales; ArgentinaFil: Zhang, Xiaomei. Shandong Tianyu Museum of Nature; ChinaFil: Zhou, Zhonghe. Chinese Academy Of Sciences. Institute of Vertebrate Paleontology and Paleoanthropology; República de Chin

IKKα inactivation promotes Kras-initiated lung adenocarcinoma development through disrupting major redox regulatory pathways.

Lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) are two distinct and predominant types of human lung cancer. IκB kinase α (IKKα) has been shown to suppress lung SCC development, but its role in ADC is unknown. We found inactivating mutations and homologous or hemizygous deletions in the CHUK locus, which encodes IKKα, in human lung ADCs. The CHUK deletions significantly reduced the survival time of patients with lung ADCs harboring KRAS mutations. In mice, lung-specific Ikkα ablation (IkkαΔLu ) induces spontaneous ADCs and promotes KrasG12D-initiated ADC development, accompanied by increased cell proliferation, decreased cell senescence, and reactive oxygen species (ROS) accumulation. IKKα deletion up-regulates NOX2 and down-regulates NRF2, leading to ROS accumulation and blockade of cell senescence induction, which together accelerate ADC development. Pharmacologic inhibition of NADPH oxidase or ROS impairs KrasG12D-mediated ADC development in IkkαΔLu mice. Therefore, IKKα modulates lung ADC development by controlling redox regulatory pathways. This study demonstrates that IKKα functions as a suppressor of lung ADC in human and mice through a unique mechanism that regulates tumor cell-associated ROS metabolism

Directional mechanical stability of Bacteriophage φ29 motor’s 3WJ-pRNA: Extraordinary robustness along portal axis

The molecular motor exploited by bacteriophage φ29 to pack DNA into its capsid is regarded as one of the most powerful mechanical devices present in viral, bacterial, and eukaryotic systems alike. Acting as a linker element, a prohead RNA (pRNA) effectively joins the connector and ATPase (adenosine triphosphatase) components of the φ29 motor. During DNA packing, this pRNA needs to withstand enormous strain along the capsid’s portal axis—how this remarkable stability is achieved remains to be elucidated. We investigate the mechanical properties of the φ29 motor’s three-way junction (3WJ)–pRNA using a combined steered molecular dynamics and atomic force spectroscopy approach. The 3WJ exhibits strong resistance to stretching along its coaxial helices, demonstrating its super structural robustness. This resistance disappears, however, when external forces are applied to the transverse directions. From a molecular standpoint, we demonstrate that this direction-dependent stability can be attributed to two Mg clamps that cooperate and generate mechanical resistance in the pRNA’s coaxial direction. Our results suggest that the asymmetric nature of the 3WJ’s mechanical stability is entwined with its biological function: Enhanced rigidity along the portal axis is likely essential to withstand the strain caused by DNA condensation, and flexibility in other directions should aid in the assembly of the pRNA and its association with other motor components

CCND1 as a Predictive Biomarker of Neoadjuvant Chemotherapy in Patients with Locally Advanced Head and Neck Squamous Cell Carcinoma

BACKGROUND: Cyclin D1 (CCND1) has been associated with chemotherapy resistance and poor prognosis. In this study, we tested the hypothesis that CCND1 expression determines response and clinical outcomes in locally advanced head and neck squamous cell carcinoma (HNSCC) patients treated with neoadjuvant chemotherapy followed by surgery and radiotherapy. METHODOLOGY AND FINDINGS: 224 patients with HNSCC were treated with either cisplatin-based chemotherapy followed by surgery and radiotherapy (neoadjuvant group, n = 100) or surgery and radiotherapy (non-neoadjuvant group, n = 124). CCND1 expression was assessed by immunohistochemistry. CCND1 levels were analyzed with chemotherapy response, disease-free survival (DFS) and overall survival (OS). There was no significant difference between the neoadjuvant group and non-neoadjuvant group in DFS and OS (p = 0.929 and p = 0.760) when patients treated with the indiscriminate administration of cisplatin-based chemotherapy. However, in the neoadjuvant group, patients whose tumors showed a low CCND1 expression more likely respond to chemotherapy (p<0.001) and had a significantly better OS and DFS than those whose tumors showed a high CCND1 expression (73% vs 8%, p<0.001; 63% vs 6%, p<0.001). Importantly, patients with a low CCND1 expression in neoadjuvant group received more survival benefits than those in non-neoadjuvant group (p = 0.016), however patients with a high CCND1 expression and treated with neoadjuvant chemotherapy had a significantly poor OS compared to those treated with surgery and radiotherapy (p = 0.032). A multivariate survival analysis also showed CCND1 expression was an independent predictive factor (p<0.001). CONCLUSIONS: This study suggests that some but not all patients with HNSCC may benefit from neoadjuvant chemotherapy with cisplatin-based regimen and CCND1 expression may serve as a predictive biomarker in selecting patients undergo less than two cycles of neoadjuvant chemotherapy

Quantum-squeezing effects of strained multilayer graphene NEMS

Quantum squeezing can improve the ultimate measurement precision by squeezing one desired fluctuation of the two physical quantities in Heisenberg relation. We propose a scheme to obtain squeezed states through graphene nanoelectromechanical system (NEMS) taking advantage of their thin thickness in principle. Two key criteria of achieving squeezing states, zero-point displacement uncertainty and squeezing factor of strained multilayer graphene NEMS, are studied. Our research promotes the measured precision limit of graphene-based nano-transducers by reducing quantum noises through squeezed states

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049