A Comparative Study on Spin-Orbit Torque Efficiencies from W/ferromagnetic and W/ferrimagnetic Heterostructures

It has been shown that W in its resistive form possesses the largest spin-Hall ratio among all heavy transition metals, which makes it a good candidate for generating efficient dampinglike spin-orbit torque (DL-SOT) acting upon adjacent ferromagnetic or ferrimagnetic (FM) layer. Here we provide a systematic study on the spin transport properties of W/FM magnetic heterostructures with the FM layer being ferromagnetic Co$_{20}$Fe$_{60}$B$_{20}$ or ferrimagnetic Co$_{63}$Tb$_{37}$ with perpendicular magnetic anisotropy. The DL-SOT efficiency $|\xi_{DL}|$, which is characterized by a current-induced hysteresis loop shift method, is found to be correlated to the microstructure of W buffer layer in both W/Co$_{20}$Fe$_{60}$B$_{20}$ and W/Co$_{63}$Tb$_{37}$ systems. Maximum values of $|\xi_{DL}|\approx 0.144$ and $|\xi_{DL}|\approx 0.116$ are achieved when the W layer is partially amorphous in the W/Co$_{20}$Fe$_{60}$B$_{20}$ and W/Co$_{63}$Tb$_{37}$ heterostructures, respectively. Our results suggest that the spin Hall effect from resistive phase of W can be utilized to effectively control both ferromagnetic and ferrimagnetic layers through a DL-SOT mechanism

Mutations in the PKM2 exon-10 region are associated with reduced allostery and increased nuclear translocation.

PKM2 is a key metabolic enzyme central to glucose metabolism and energy expenditure. Multiple stimuli regulate PKM2's activity through allosteric modulation and post-translational modifications. Furthermore, PKM2 can partner with KDM8, an oncogenic demethylase and enter the nucleus to serve as a HIF1α co-activator. Yet, the mechanistic basis of the exon-10 region in allosteric regulation and nuclear translocation remains unclear. Here, we determined the crystal structures and kinetic coupling constants of exon-10 tumor-related mutants (H391Y and R399E), showing altered structural plasticity and reduced allostery. Immunoprecipitation analysis revealed increased interaction with KDM8 for H391Y, R399E, and G415R. We also found a higher degree of HIF1α-mediated transactivation activity, particularly in the presence of KDM8. Furthermore, overexpression of PKM2 mutants significantly elevated cell growth and migration. Together, PKM2 exon-10 mutations lead to structure-allostery alterations and increased nuclear functions mediated by KDM8 in breast cancer cells. Targeting the PKM2-KDM8 complex may provide a potential therapeutic intervention

Cervarix™: a vaccine for the prevention of HPV 16, 18-associated cervical cancer

Cervical cancer continues to be the second largest cause of cancer deaths in women worldwide. Persistent infection with high-risk types of human papillomavirus (HPV) is a necessary cause of cervical cancer. Thus, prophylactic vaccination against HPV is an attractive strategy to prevent cervical cancer. Current strategies for the development of safe and effective preventive vaccines are based on the induction of neutralizing antibodies against the major capsid protein, L1 of HPV. Cervarix™ is one of the preventive HPV vaccines that has been approved in the Europe and Australia and is currently under review by the US Food and Drug Administration. Cervarix is composed of HPV16 and HPV18 L1 virus-like particles (VLPs) formulated in ASO4 adjuvant. Vaccination with Cervarix has been shown to protect women against a high proportion of precursor lesions of cervical cancer caused by these two HPV types. This review explores the various features of this new vaccine candidate and discusses the future directions in the field of HPV vaccine development

Improving therapeutic HPV peptide-based vaccine potency by enhancing CD4+ T help and dendritic cell activation

<p>Abstract</p> <p>Background</p> <p>Effective vaccination against human papillomavirus (HPV) represents an opportunity to control cervical cancer. Peptide-based vaccines targeting HPV E6 and/or E7 antigens while safe, will most likely require additional strategies to enhance the vaccine potency.</p> <p>Methods</p> <p>We tested the HPV-16 E7 peptide-based vaccine in combination with a strategy to enhance CD4+ T help using a Pan HLA-DR epitope (PADRE) peptide and a strategy to enhance dendritic cell activation using the toll-like receptor 3 ligand, poly(I:C).</p> <p>Results</p> <p>We observed that mice vaccinated with E7 peptide-based vaccine in combination with PADRE peptide and poly(I:C) generated better E7-specific CD8⁺T cell immune responses as well as significantly improved therapeutic anti-tumor effects against TC-1 tumors compared to E7 peptide-based vaccine with either PADRE peptide or poly(I:C) alone. Furthermore, we found that intratumoral vaccination with the E7 peptide in conjunction with PADRE peptide and poly(I:C) generates a significantly higher frequency of E7-specific CD8⁺T cells as well as better survival compared to subcutaneous vaccination with the same regimen in treated mice.</p> <p>Conclusions</p> <p>The combination of PADRE peptide and poly(I:C) with antigenic peptide is capable of generating potent antigen-specific CD8+ T cell immune responses and antitumor effects in vaccinated mice. Our study has significant clinical implications for peptide-based vaccination.</p

A Simple Fiber Bragg Grating-Based Sensor Network Architecture with Self-Protecting and Monitoring Functions

A novel fiber Bragg grating (FBG)-based passive sensor architecture, which can be used to protect the fiber cut and monitor the multiple sensors simultaneously, is proposed and experimentally demonstrated. Here, we employ a wavelength-tunable erbium-doped fiber (EDF) laser scheme with 25 km cavity length acting as the detecting light source in central office (CO). Each FBG sensor, serving as a feedback element, is used in proposed sensor architecture. By tuning the tunable bandpass filter (TBF) placing inside cavity to match the corresponding Bragg wavelength of FBG over the amplification bandwidth, we can retrieve the related wavelength lasing for the FBG sensing and monitoring simultaneously. Moreover, the survivability and capacity of the passive FBG sensor architecture can be also enhanced

On the Improvement of Wiener Attack on RSA with Small Private Exponent

RSA system is based on the hardness of the integer factorization problem (IFP). Given an RSA modulus N=pq, it is difficult to determine the prime factors p and q efficiently. One of the most famous short exponent attacks on RSA is the Wiener attack. In 1997, Verheul and van Tilborg use an exhaustive search to extend the boundary of the Wiener attack. Their result shows that the cost of exhaustive search is 2r+8 bits when extending the Weiner's boundary r bits. In this paper, we first reduce the cost of exhaustive search from 2r+8 bits to 2r+2 bits. Then, we propose a method named EPF. With EPF, the cost of exhaustive search is further reduced to 2r-6 bits when we extend Weiner's boundary r bits. It means that our result is 214 times faster than Verheul and van Tilborg's result. Besides, the security boundary is extended 7 bits

Vascular disrupting agent DMXAA enhances the antitumor effects generated by therapeutic HPV DNA vaccines

Antigen-specific immunotherapy using DNA vaccines has emerged as an attractive approach for the control of tumors. Another novel cancer therapy involves the employment of the vascular disrupting agent, 5,6-dimethylxanthenone-4-acetic acid (DMXAA). In the current study, we aimed to test the combination of DMXAA treatment with human papillomavirus type 16 (HPV-16) E7 DNA vaccination to enhance the antitumor effects and E7-specific CD8+ T cell immune responses in treated mice. We determined that treatment with DMXAA generates significant therapeutic effects against TC-1 tumors but does not enhance the antigen-specific immune responses in tumor bearing mice. We then found that combination of DMXAA treatment with E7 DNA vaccination generates potent antitumor effects and E7-specific CD8+ T cell immune responses in the splenocytes of tumor bearing mice. Furthermore, the DMXAA-mediated enhancement or suppression of E7-specific CD8+ T cell immune responses generated by CRT/E7 DNA vaccination was found to be dependent on the time of administration of DMXAA and was also applicable to other antigen-specific vaccines. In addition, we determined that inducible nitric oxide synthase (iNOS) plays a role in the immune suppression caused by DMXAA administration before DNA vaccination. Our study has significant implications for future clinical translation