Structural features of human immunoglobulin G that determine isotype-specific differences in complement activation.

Although very similar in sequence, the four subclasses of human immunoglobulin G (IgG) differ markedly in their ability to activate complement. Glu318-Lys320-Lys322 has been identified as a key binding motif for the first component of complement, C1q, and is present in all isotypes of Ig capable of activating complement. This motif, however, is present in all subclasses of human IgG, including those that show little (IgG2) or even no (IgG4) complement activity. Using point mutants of chimeric antibodies, we have identified specific residues responsible for the differing ability of the IgG subclasses to fix complement. In particular, we show that Ser at position 331 in gamma 4 is critical for determining the inability of that isotype to bind C1q and activate complement. Additionally, we provide further evidence that levels of C1q binding do not necessarily correlate with levels of complement activity, and that C1q binding alone is not sufficient for complement activation

The differential ability of human IgG1 and IgG4 to activate complement is determined by the COOH-terminal sequence of the CH2 domain.

Using domain switch chimeric antibodies, we confirm the important role of CH2 in complement activation. In addition, we demonstrate that the structures responsible for the differential ability of human IgG1 and IgG4 to activate complement are located at the COOH-terminal part (from residue 292 to 340) of the CH2 domain. The amino acids in CH2 that might be involved in complement interaction are discussed. While CH3 contributes to efficient complement activation, CH3 from IgG2 and CH3 IgG3 are equally effective

Dynamic Behavior of Droplet Impact on Inclined Surfaces with Acoustic Waves

Droplet impact on arbitrary inclined surfaces is of great interest for applications such as antifreezing, self-cleaning, and anti-infection. Research has been focused on texturing the surfaces to alter the contact time and rebouncing angle upon droplet impact. In this paper, using propagating surface acoustic waves (SAWs) along the inclined surfaces, we present a novel technique to modify and control key droplet impact parameters, such as impact regime, contact time, and rebouncing direction. A high-fidelity finite volume method was developed to explore the mechanisms of droplet impact on the inclined surfaces assisted by SAWs. Numerical results revealed that applying SAWs modifies the energy budget inside the liquid medium, leading to different impact behaviors. We then systematically investigated the effects of inclination angle, droplet impact velocity, SAW propagation direction, and applied SAW power on the impact dynamics and showed that by using SAWs, droplet impact on the nontextured hydrophobic and inclined surface is effectively changed from deposition to complete rebound. Moreover, the maximum contact time reduction up to ∼50% can be achieved, along with an alteration of droplet spreading and movement along the inclined surfaces. Finally, we showed that the rebouncing angle along the inclined surface could be adjusted within a wide range

Jet Trimming

Initial state radiation, multiple interactions, and event pileup can contaminate jets and degrade event reconstruction. Here we introduce a procedure, jet trimming, designed to mitigate these sources of contamination in jets initiated by light partons. This procedure is complimentary to existing methods developed for boosted heavy particles. We find that jet trimming can achieve significant improvements in event reconstruction, especially at high energy/luminosity hadron colliders like the LHC.Comment: 20 pages, 11 figures, 3 tables - Minor changes to text/figure

Quantum noise protects quantum classifiers against adversaries

Noise in quantum information processing is often viewed as a disruptive and difficult-to-avoid feature, especially in near-term quantum technologies. However, noise has often played beneficial roles, from enhancing weak signals in stochastic resonance to protecting the privacy of data in differential privacy. It is then natural to ask: Can we harness the power of quantum noise that is beneficial to quantum computing? An important current direction for quantum computing is its application to machine learning, such as classification problems. One outstanding problem in machine learning for classification is its sensitivity to adversarial examples. These are small, undetectable perturbations from the original data where the perturbed data is completely misclassified in otherwise extremely accurate classifiers. They can also be considered as worst-case perturbations by unknown noise sources. We show that by taking advantage of depolarization noise in quantum circuits for classification, a robustness bound against adversaries can be derived where the robustness improves with increasing noise. This robustness property is intimately connected with an important security concept called differential privacy, which can be extended to quantum differential privacy. For the protection of quantum data, this quantum protocol can be used against the most general adversaries. Furthermore, we show how the robustness in the classical case can be sensitive to the details of the classification model, but in the quantum case the details of the classification model are absent, thus also providing a potential quantum advantage for classical data. This opens the opportunity to explore other ways in which quantum noise can be used in our favor, as well as identifying other ways quantum algorithms can be helpful in a way which is distinct from quantum speedups

Wide range of droplet jetting angles by thin-film based surface acoustic waves

Nozzleless jetting of droplets with different jetting angles is a crucial requirement for 2D and 3D printing/bioprinting applications, and Rayleigh mode surface acoustic waves (SAWs) could be a potential technique for achieving this purpose. Currently, it is critical to vary the jetting angles of liquid droplets induced by SAWs and control the liquid jet directions. Generally, the direction of the liquid jet induced by SAWs generated from a bulk piezoelectric substrate such as LiNbO_{3} is along the theoretical Rayleigh angle of ∼22°. In this study, we designed and manufactured thin-film SAW devices by depositing ZnO films on different substrates (including silicon and aluminium) to realize a wide range of jetting angles from ∼16° to 55° using propagating waves generated from one interdigital transducer. We then systematically investigated different factors affecting the jetting angles, including liquid properties, applied SAW power and SAW device resonant frequency. Finally, we proposed various methods using thin-film SAW devices together with different transducer designs for realizing a wide range of jetting angles within the 3D domain. A nozzleless jetting method is proposed using thin-film based surface acoustic wave devices to achieve a wide range of jetting angles for droplets

Thin film Gallium nitride (GaN) based acoustofluidic Tweezer: Modelling and microparticle manipulation.

Gallium nitride (GaN) is a compound semiconductor which shows advantages in new functionalities and applications due to its piezoelectric, optoelectronic, and piezo-resistive properties. This study develops a thin film GaN-based acoustic tweezer (GaNAT) using surface acoustic waves (SAWs) and demonstrates its acoustofluidic ability to pattern and manipulate microparticles. Although the piezoelectric performance of the GaNAT is compromised compared with conventional lithium niobate-based SAW devices, the inherited properties of GaN allow higher input powers and superior thermal stability. This study shows for the first time that thin film GaN is suitable for the fabrication of the acoustofluidic devices to manipulate microparticles with excellent performance. Numerical modelling of the acoustic pressure fields and the trajectories of mixtures of microparticles driven by the GaNAT was performed and the results were verified from the experimental studies using samples of polystyrene microspheres. The work has proved the robustness of thin film GaN as a candidate material to develop high-power acoustic tweezers, with the potential of monolithical integration with electronics to offer diverse microsystem applications.Engineering and Physical Sciences Research Council Grant numbers: EP/P002803/1, EP/P018998/1, Natural Science Basic Research Program of Shaanxi Province/2020JQ-233, Fundamental Scientific Research of Central Universities/3102017OQD116, Engineering and Physical Sciences Research Council fellowship /EP/N01202X/2, Royal Society / IEC/NSFC/170142, IE161019, Natural Science Foundation of China/61704017, Dalian Science and Technology Innovation Fund/2018J11CY00

Heavy Squarks at the LHC

The LHC, with its seven-fold increase in energy over the Tevatron, is capable of probing regions of SUSY parameter space exhibiting qualitatively new collider phenomenology. Here we investigate one such region in which first generation squarks are very heavy compared to the other superpartners. We find that the production of these squarks, which is dominantly associative, only becomes rate-limited at mSquark > 4(5) TeV for L~10(100) fb-1. However, discovery of this scenario is complicated because heavy squarks decay primarily into a jet and boosted gluino, yielding a dijet-like topology with missing energy (MET) pointing along the direction of the second hardest jet. The result is that many signal events are removed by standard jet/MET anti-alignment cuts designed to guard against jet mismeasurement errors. We suggest replacing these anti-alignment cuts with a measurement of jet substructure that can significantly extend the reach of this channel while still removing much of the background. We study a selection of benchmark points in detail, demonstrating that mSquark= 4(5) TeV first generation squarks can be discovered at the LHC with L~10(100)fb-1

Exploring hypotheses of the actions of TGF-beta 1 in epidermal wound healing using a 3D computational multiscale model of the human epidermis

In vivo and in vitro studies give a paradoxical picture of the actions of the key regulatory factor TGF-beta 1 in epidermal wound healing with it stimulating migration of keratinocytes but also inhibiting their proliferation. To try to reconcile these into an easily visualized 3D model of wound healing amenable for experimentation by cell biologists, a multiscale model of the formation of a 3D skin epithelium was established with TGF-beta 1 literature-derived rule sets and equations embedded within it. At the cellular level, an agent-based bottom-up model that focuses on individual interacting units ( keratinocytes) was used. This was based on literature-derived rules governing keratinocyte behavior and keratinocyte/ECM interactions. The selection of these rule sets is described in detail in this paper. The agent-based model was then linked with a subcellular model of TGF-beta 1 production and its action on keratinocytes simulated with a complex pathway simulator. This multiscale model can be run at a cellular level only or at a combined cellular/subcellular level. It was then initially challenged ( by wounding) to investigate the behavior of keratinocytes in wound healing at the cellular level. To investigate the possible actions of TGF-beta 1, several hypotheses were then explored by deliberately manipulating some of these rule sets at subcellular levels. This exercise readily eliminated some hypotheses and identified a sequence of spatial-temporal actions of TGF-beta 1 for normal successful wound healing in an easy-to-follow 3D model. We suggest this multiscale model offers a valuable, easy-to-visualize aid to our understanding of the actions of this key regulator in wound healing, and provides a model that can now be used to explore pathologies of wound healing

Integration of chromosomal microarray into paediatric clinical care in Hong Kong

Poster Presentation 9BACKGROUND AND AIMS: Chromosomal microarray (CMA) has emerged as a major tool to identify unbalanced chromosomal aberrations in children and is recommended as the first tiered investigation for intellectual disability, autism spectrum disorders and multiple congenital anomalies. While the clinical interpretation and genetic counseling remain as ongoing challenge, data about potential downstream benefits and harms of CMA is lacking, especially in paediatric ...postprin