Reliable Password Hardening Service with Opt-Out

As the most dominant authentication mechanism, password-based authentication suffers catastrophic offline password guessing attacks once the authentication server is compromised and the password database is leaked. Password hardening (PH) service, an external/third-party crypto service, has been recently proposed to strengthen password storage and reduce the damage of authentication server compromise. However, all existing schemes are unreliable because they overlook the important restorable property: PH service opt-out. In existing PH schemes, once the authentication server has subscribed to a PH service, it must adopt this service forever, even if it wants to stop the external/third-party PH service and restore its original password storage (or subscribe to another PH service). To fill the gap, we propose a new PH service called PW-Hero that equips its PH service with an option to terminate its use (i.e., opt-out). In PW-Hero, password authentication is strengthened against offline attacks by adding external secret spices to password records. With the opt-out property, authentication servers can proactively request to end the PH service after successful authentications. Then password records can be securely migrated to their traditional salted hash state, ready for subscription to other PH services. Besides, PW-Hero achieves all existing desirable properties, such as comprehensive verifiability, rate limits against online attacks, and user privacy. We define PW-Hero as a suite of protocols that meet desirable properties and build a simple, secure, and efficient instance. Moreover, we develop a prototype implementation and evaluate its performance, which shows the practicality of our PW-Hero service

Adaptive Hybrid Visual Servo Regulation of Mobile Robots Based on Fast Homography Decomposition

For the monocular camera-based mobile robot system, an adaptive hybrid visual servo regulation algorithm which is based on a fast homography decomposition method is proposed to drive the mobile robot to its desired position and orientation, even when object’s imaging depth and camera’s position extrinsic parameters are unknown. Firstly, the homography’s particular properties caused by mobile robot’s 2-DOF motion are taken into account to induce a fast homography decomposition method. Secondly, the homography matrix and the extracted orientation error, incorporated with the desired view’s single feature point, are utilized to form an error vector and its open-loop error function. Finally, Lyapunov-based techniques are exploited to construct an adaptive regulation control law, followed by the experimental verification. The experimental results show that the proposed fast homography decomposition method is not only simple and efficient, but also highly precise. Meanwhile, the designed control law can well enable mobile robot position and orientation regulation despite the lack of depth information and camera’s position extrinsic parameters

Effect of tRF-Pro-CGG on the biological behavior of mouse pancreatic cancer cells and its molecular mechanism

Background and purpose: tRNA-derived fragments (tRF) are a kind of short non-coding RNA (14-30 nt) that influences the course of cancer. This study aimed to investigate the molecular pathways that might underlie the effects of tRF-Pro-CGG on the biological behavior of mouse pancreatic cancer cells. Methods: Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) was used to assess the expression of tRF-Pro-CGG in mouse pancreatic cancer cell lines pan02 and LTPA, human pancreatic cancer cell line Capan-2, and normal pancreatic cells HPDE6-C7. tRF-Pro-CGG overexpression in pan02 cells and LTPA cell suppression were achieved through lentiviral transfection, and RTFQ-PCR and Western blot were used to determine overexpression and knockdown effects. Cell counting kit-8 (CCK-8) was used to detect cell proliferation. Transwell assays were used to detect cell migration and invasion ability. The effect of tRF-Pro-CGG on the growth and metastasis of pancreatic cancer transplantation tumors in nude mice model was investigated. H-E staining was used to observe the histopathological structure of transplantation tumors. Western blot was used to detect the expression and phosphorylation of proliferation-related protein Ki-67 and metastasis-related proteins. Western blot was used to assess the expressions of cadherin, vimentin, phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway protein and phosphorylation in transplanted tumor tissues. Results: tRF-Pro-CGG expression was lowest in the mouse pancreatic cancer cell line pan02. Both mRNA and protein expression levels of tRF-Pro-CGG were significantly increased (P <0.01) after transfection of tRF-Pro-CGG mimics in pan02 cells, and cell proliferation ability (P<0.01), cell migration (P<0.001) and invasion ability (P<0.001) were significantly reduced. A significant decrease in the volume (P<0.01) and weight (P<0.001) of transplanted tumors in nude mice was observed, and significant necrotic and apoptotic cells in transplanted tumor were identified. In transplanted tumor tissues of nude mice, the Ki-67 proliferatien index and expression of vimentin were significantly decreased (P<0.001), while E-cadherin was increased (P<0.001). The expressions of PI3K, P-PI3K, AKT and P-AKT were significantly decreased (P<0.001). There was no significant difference in the number of liver metastases from pancreatic cancer (P>0.05). The mouse pancreatic cancer cell line LTPA had the greatest level of tRF-Pro-CGG expression. The mRNA and protein expression levels of tRF-Pro-CGG were significantly reduced (P<0.01) after transfection of tRF-Pro-CGG inhibitor in LTPA cells. The proliferation ability of cells was significantly increased (P<0.01), the migration of cells (P<0.001) and invasive ability (P<0.001) were significantly increased. The volume (P<0.01) and weight (P<0.01) of transplanted tumors in nude mice were significantly increased, and a limited proportion of necrotic and apoptotic cells were seen in nude mice tumor tissues implanted. In the transplanted tumor tissues of nude mice, the Ki-67 proliferation index and expression of vimentin were significantly increased (P<0.001), while E-cadherin was decreased (P<0.001). The expressions of PI3K, P-PI3K, AKT, and P-AKT were significantly increased (P<0.001). There was no difference in the number of liver metastases from pancreatic cancer (P>0.05). Conclusion: Overexpression of tRF-Pro-CGG reduced pancreatic cancer cell proliferation, migration and invasion in mice, slowed the formation of pancreatic cancer transplanted tumors in nude mice, and decreased Ki-67 proliferation index and expression of vimentin and PI3K/AKT phosphorylation levels. The PI3K/AKT signaling pathway may be regulated by tRF-Pro-CGG, which may suppress the development of pancreatic cancer

Purification, Characterization and Antitumor Activities of a New Protein from Syngnathus acus, an Officinal Marine Fish

Discovery and development of new antitumor agents from abundant marine fish are attracting an increasing interest. In the present study, we extracted and purified a novel antitumor protein Syngnathusin from the whole body of Syngnathus acus L., a precious marine fish traditionally used for tumors. Syngnathusin was comprised of 16 kinds of amino acids, mainly acidic amino acids. Its molecular weight was 67.3 kDa and its isoelectric point was 4.57. The N-terminal amino acid sequence of Syngnathusin was determined to be Lys-Arg-Asp-Leu-Gly-Phe-Val-Asp-Glu-Ile-Ser-Ala-His-Tyr and showed no significant homology with the known proteins. Syngnathusin could significantly inhibit the growth of A549 and CCRF-CEM cells. However, the obvious proliferation inhibition against human non-tumor cell lines was not observed. Flow cytometry, morphologic assessment and comet assay revealed that Syngnathusin could induce apoptosis in A549 and CCRF-CEM cells and strongly cooperated with MTX. Syngnathusin could inhibit the growth of S180 tumor transplanted in mice. Syngnathusin may be developed as a novel, selective and effective antineoplastic agent

Improvement of Morphine-Mediated Analgesia by Inhibition of β-Arrestin 2 Expression in Mice Periaqueductal Gray Matter

Morphine is a well-known μ-opioid receptor (MOR) agonist and an efficient analgesic, but its long-term use inevitably leads to drug addiction and tolerance. Here, we show that specific inhibition of β-arrestin2 with its siRNA lentivirus microinjected in mice periaqueductal gray matter (PAG) significantly improved both acute and chronic morphine analgesia and delayed the tolerance in the hotplate test. The specific effect of β-arrestin2 was proven by overexpression or knockdown of its homology β-arrestin1 in PAG, which showed no significant effects on morphine analgesia. These findings suggest that specific siRNA targeting β-arrestin2 may constitute a new approach to morphine therapy and other MOR agonist-mediated analgesia and tolerance

Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect. Nature

The worldwide prevalence of chronic hepatitis C virus (HCV) infection is estimated to be approaching 200 million people We designed a mechanistically unbiased approach based on chemical genetics to identify chemical starting points for interfering with HCV replication. Our differentiating strategy centred on the identification of compounds functionally distinct from those acting on the traditional targets of antiviral research in this field, the NS3 protease and the NS5B RNA-dependent RNA polymerase 10 . BMS-858 formed the basis of an extensive series of chemical refinements that focused on improving antiviral potency, broadening inhibitory activity to encompass the HCV 1a genotype, and optimizing for oral bioavailability and sustained pharmacokinetic properties. After defining symmetry as an important contributor to antiviral activity 10 , a discovery that preceded the disclosure of structural information (see below), we subsequently identified BMS-79005