Structural basis of immunosuppression by the therapeutic antibody daclizumab

Interleukin-2 （IL）-2 signaling plays a pivotal role in the activation of immune responses, and drugs that block this pathway have been shown to be effective for the immunosuppression in patients with organ transplantation to alleviate/eliminate allograft rejection. The first humanized monoclonal antibody （mAb） daclizumab falls into this category and shows high specificity and affinity against a key component of the IL-2 receptor complex, namely IL-2Ra. To reveal the molecular mechanism of the inhibition of the IL-2 signaling pathway by dacllzumab, we determined the crystal structures of the daclizumab Fab in free form and in complex with the IL-2Ra ectodomain at 2.6 and 2.8 A resolution, respectively. The daclizumab Fab adopts a similar conformation in the presence or absence of the IL- 2Ra ectodomain. The antigen-binding site of daclizumab is mainly composed of live complementarity determining regions （CDRs） that form a large positively charged surface depression and two flanking patches that are generally hydrophobic. The conformational epitope consists of several discontinuous segments of the IL-2Ru ectodomain, a large portion of which overlaps with the regions that interact with IL-2, suggesting that the binding of daclizumab to IL-2Ra would prevent the IL-2 binding to IL-2Ra and the subsequent formation of the IL-2fIL-2Ra[~/c complex, and therefore block the IL-2 signaling pathway. These results also have implications for the design and development of improved mAb drugs targeting IL-2Ra.

T Cell Receptor Signaling Pathways:New Targets for Herpes Simplex Virus

Herpes simplex viruses （HSV-1 and HSV-2） cause global morbidity and synergistically correlate with HIV infection. HSV exists life-long in a latent form in sensory neurons with intermittent reactivation, in despite of host immune surveillatlce. While abundant evidence for HSV interfering with innate immune responses so as to favor the replication and propagation of the virus, several lines of evidence declare that HSV attenuates adaptive immunity by various mechanisms, including but not limited to the ablation of antigen presentation, induction of apoptosis, and interruption of cellular signaling. In this review, we will focus on the perturbative role of HSV in T cells signaling.

Digital Public Communication in Europe for a European Public Sphere

In the last years, Europe has aimed at the creation of a new European public sphere that has grown beside and has not replaced the national ones; a public sphere in which the idea of Europe as a shared value, as a reality of nations, but also as a reality of regions and cities, can build and develop. This aim is the result of a long discussion that has led to consider the public communication as a fundamental instrument supporting the dialogue between institutions and citizens and the result of an important sociological debate. Communication is nowadays considered as a structural element of Union＇s programs, and the transformation of the media system, the possibilities of communication offered by the social media, and the growth of participatory cultures have opened new ways to the development of European public communication that can contribute to increasing the European public sphere. This process involves an awareness from institutions and their representatives on the use of social media （e.g., Facebook, Twitter, etc.） to improve the relationship with the citizens and to create a sense of belonging to Europe.

A novel flexure-based uniaxial force sensor with large range and high resolution

High performance force sensors often encounter the conflicting requirements of high resolution and large measurement range.To address this problem,this paper presents a conceptual design of a novel uniaxial force sensor with large range and dual-stage force resolutions which enables us to measure forces within a wide range with satisfied resolutions.The newly developed force sensor features an aluminum alloy body with a probe to transfer external forces into the sensing element.It employs an optical linear encoder to detect the displacement of the sensing body.This sensing scheme may immunize outside electromagnetic noises and therefore enhance the performance of the sensor thanks to its digital signal output.In this paper,an accurate,analytical model for calculating the static stiffness and dynamics of the system was developed by using pseudo-rigid-body-model(PRBM)methodology.To optimize the design,finite element simulations were conducted.After a prototype sensor was fabricated,preliminary characterization tests were carried out to verify the accuracy of the theoretical model and demonstrate the effectiveness of the design.The experiment results indicate that the structure of the new sensor is compact,and it has the ability to measure both micro range and macro range forces within one setup,meanwhile keeps very fine resolutions.

Rabi oscillation generation in the microring resonator system with double-series ring resonators

In this paper, a microring resonator(MRR) system using double-series ring resonators is proposed to generate and investigate the Rabi oscillations. The system is made up of silicon-on-insulator and attached to bus waveguide which is used as propagation and oscillation medium. The scattering matrix method is employed to determine the output signal intensity which acts as the input source between two-level Rabi oscillation states, where the increase of Rabi oscillation frequency with time is obtained at the resonant state. The population probability of the excited state is higher and unstable at the optical resonant state due to the nonlinear spontaneous emission process. The enhanced spontaneous emission can be managed by the atom(photon) excitation, which can be useful for atomic related sensors and single-photon source applications.