Efficient Algorithms for Optimal 4-Bit Reversible Logic System Synthesis

Owing to the exponential nature of the memory and run-time complexity, many methods can only synthesize 3-bit reversible circuits and cannot synthesize 4-bit reversible circuits well. We mainly absorb the ideas of our 3-bit synthesis algorithms based on hash table and present the efficient algorithms which can construct almost all optimal 4-bit reversible logic circuits with many types of gates and at mini-length cost based on constructing the shortest coding and the specific topological compression; thus, the lossless compression ratio of the space of n-bit circuits reaches near 2×n!. This paper presents the first work to create all 3120218828 optimal 4-bit reversible circuits with up to 8 gates for the CNT (Controlled-NOT gate, NOT gate, and Toffoli gate) library, and it can quickly achieve 16 steps through specific cascading created circuits

Detection of cigarette appearance defects based on improved YOLOv4

Appearance defects are visible factors that affect the quality of cigarettes. Most of the consumer complaints received by tobacco companies are caused by appearance defects of cigarettes. Therefore, it is of great significance to reduce cigarettes with appearance defects. At present, tobacco factories mainly detect the appearance quality of cigarettes through manual sampling inspection. The manual method has low detection efficiency, it is difficult to unify the judgment standard, and it is easy to cause secondary pollution to cigarettes. According to the features of cigarette appearance defects, the YOLOv4 (You Only Look Once Version 4) model was improved for cigarette appearance defect detection. We have improved the following: 1) the channel attention mechanism was introduced into YOLOv4 to improve the detection precision; 2) the K-means++ algorithm was used to optimize the selection of clustering centers; 3) the spatial pyramid pooling (SPP) was replaced with atrous spatial pyramid pooling (ASPP) to improve the defect detection ability with different sizes; 4) the α-CIoU loss function was used to improve the detection precision. The mAP of our improved method reached 91.77%, the precision reached 93.32%, and the recall reached 88.81%. Compared with other models, our method has better comprehensive performance and better detection ability

Discovery of Novel 2-Aminopyridine Derivatives As ROS1 and ALK Dual Inhibitors to Combat Drug-Resistant Mutants including ROS1G2032R and ALKG1202R

Clinical treatment by FDA-approved ROS1/ALK inhibitor Crizotinib significantly improved the therapeutic outcomes. However, the emergence of drug resistance, especially driven by acquired mutations, have become an inevitable problem and worsened the clinical effects of Crizotinib. To combat drug resistance, some novel 2-aminopyridine derivatives were designed rationally based on molecular simulation, then synthesised and subjected to biological test. The preferred spiro derivative C01 exhibited remarkable activity against CD74-ROS1G2032R cell with an IC50 value of 42.3 nM, which was about 30-fold more potent than Crizotinib. Moreover, C01 also potently inhibited enzymatic activity against clinically Crizotinib-resistant ALKG1202R, harbouring a 10-fold potency superior to Crizotinib. Furthermore, molecular dynamic disclosed that introducing the spiro group could reduce the steric hindrance with bulky side chain (Arginine) in solvent region of ROS1G2032R, which explained the sensitivity of C01 to drug-resistant mutant. These results indicated a path forward for the generation of anti Crizotinib-resistant ROS1/ALK dual inhibitors

Overexpression of TUF1 restores respiratory growth and fluconazole sensitivity to a Cryptococcus neoformans vad1Δ mutant

The yeast-like fungus Cryptococcus neoformans favours respiration as a mechanism of energy production, and thus depends heavily on mitochondrial function. Previous studies of a C. neoformans vad1Δ mutant revealed reduced expression of the mitochondrial elongation factor TUF1 and defects in glycerol utilization, consistent with mitochondrial dysfunction. In this study, we found that in trans expression of TUF1 in the vad1Δ mutant suppressed the mitochondrial defects, including growth on respiration-dependent carbon sources and fluconazole resistance, associated with VAD1 deletion. Tetracycline, an inhibitor of mitochondrial translation, was found to confer resistance to fluconazole in the wild-type and vad1Δ mutant, whereas the fluconazole susceptibility of the TUF1-overexpressing strain was unaffected by tetracycline treatment. In the presence of fluconazole, the vad1Δ mutant exhibited increased activation of the global transcriptional regulator Sre1. TUF1 overexpression failed to alter cleavage of Sre1 in response to fluconazole in the vad1Δ mutant, suggesting that TUF1 repression in the vad1Δ mutant is distal to Sre1, or that it occurs through an independent pathway

Perioperative Toripalimab Plus Chemotherapy for Patients With Resectable Non-Small Cell Lung Cancer: The Neotorch Randomized Clinical Trial

IMPORTANCE: Adjuvant and neoadjuvant immunotherapy have improved clinical outcomes for patients with early-stage non-small cell lung cancer (NSCLC). However, the optimal combination of checkpoint inhibition with chemotherapy remains unknown. OBJECTIVE: To determine whether toripalimab in combination with platinum-based chemotherapy will improve event-free survival and major pathological response in patients with stage II or III resectable NSCLC compared with chemotherapy alone. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial enrolled patients with stage II or III resectable NSCLC (without EGFR or ALK alterations for nonsquamous NSCLC) from March 12, 2020, to June 19, 2023, at 50 participating hospitals in China. The data cutoff date for this interim analysis was November 30, 2022. INTERVENTIONS: Patients were randomized in a 1:1 ratio to receive 240 mg of toripalimab or placebo once every 3 weeks combined with platinum-based chemotherapy for 3 cycles before surgery and 1 cycle after surgery, followed by toripalimab only (240 mg) or placebo once every 3 weeks for up to 13 cycles. MAIN OUTCOMES AND MEASURES: The primary outcomes were event-free survival (assessed by the investigators) and the major pathological response rate (assessed by blinded, independent pathological review). The secondary outcomes included the pathological complete response rate (assessed by blinded, independent pathological review) and adverse events. RESULTS: Of the 501 patients randomized, 404 had stage III NSCLC (202 in the toripalimab + chemotherapy group and 202 in the placebo + chemotherapy group) and 97 had stage II NSCLC and were excluded from this interim analysis. The median age was 62 years (IQR, 56-65 years), 92% of patients were male, and the median follow-up was 18.3 months (IQR, 12.7-22.5 months). For the primary outcome of event-free survival, the median length was not estimable (95% CI, 24.4 months-not estimable) in the toripalimab group compared with 15.1 months (95% CI, 10.6-21.9 months) in the placebo group (hazard ratio, 0.40 [95% CI, 0.28-0.57], P \u3c .001). The major pathological response rate (another primary outcome) was 48.5% (95% CI, 41.4%-55.6%) in the toripalimab group compared with 8.4% (95% CI, 5.0%-13.1%) in the placebo group (between-group difference, 40.2% [95% CI, 32.2%-48.1%], P \u3c .001). The pathological complete response rate (secondary outcome) was 24.8% (95% CI, 19.0%-31.3%) in the toripalimab group compared with 1.0% (95% CI, 0.1%-3.5%) in the placebo group (between-group difference, 23.7% [95% CI, 17.6%-29.8%]). The incidence of immune-related adverse events occurred more frequently in the toripalimab group. No unexpected treatment-related toxic effects were identified. The incidence of grade 3 or higher adverse events, fatal adverse events, and adverse events leading to discontinuation of treatment were comparable between the groups. CONCLUSIONS AND RELEVANCE: The addition of toripalimab to perioperative chemotherapy led to a significant improvement in event-free survival for patients with resectable stage III NSCLC and this treatment strategy had a manageable safety profile. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04158440

An Appearance Defect Detection Method for Cigarettes Based on C-CenterNet

Due to the poor adaptability of traditional methods in the cigarette detection task on the automatic cigarette production line, it is difficult to accurately identify whether a cigarette has defects and the types of defects; thus, a cigarette appearance defect detection method based on C-CenterNet is proposed. This detector uses keypoint estimation to locate center points and regresses all other defect properties. Firstly, Resnet50 is used as the backbone feature extraction network, and the convolutional block attention mechanism (CBAM) is introduced to enhance the network’s ability to extract effective features and reduce the interference of non-target information. At the same time, the feature pyramid network is used to enhance the feature extraction of each layer. Then, deformable convolution is used to replace part of the common convolution to enhance the learning ability of different shape defects. Finally, the activation function ACON (ActivateOrNot) is used instead of the ReLU activation function, and the activation operation of some neurons is adaptively selected to improve the detection accuracy of the network. The experimental results are mainly acquired via the mean Average Precision (mAP). The experimental results show that the mAP of the C-CenterNet model applied in the cigarette appearance defect detection task is 95.01%. Compared with the original CenterNet model, the model’s success rate is increased by 6.14%, so it can meet the requirements of precision and adaptability in cigarette detection tasks on the automatic cigarette production line

Inductive Method for Evaluating RFID Security Protocols

Authentication protocol verification is a difficult problem. The problem of “state space explosion” has always been inevitable in the field of verification. Using inductive characteristics, we combine mathematical induction and model detection technology to solve the problem of “state space explosion” in verifying the OSK protocol and VOSK protocol of RFID system. In this paper, the security and privacy of protocols in RFID systems are studied and analysed to verify the effectiveness of the combination of mathematical induction and model detection. We design a (r,s,t)-security experiment on the basis of privacy experiments in the RFID system according to the IND-CPA security standard in cryptography, using mathematical induction to validate the OSK protocol and VOSK protocol. Finally, the following conclusions are presented. The OSK protocol cannot resist denial of service attacks or replay attacks. The VOSK protocol cannot resist denial of service attacks but can resist replay attacks. When there is no limit on communication, the OSK protocol and VOSK protocol possess (r,s,t)-privacy; that is to say they can resist denial of service attacks