A Zika virus-specific IgM elicited in pregnancy exhibits ultrapotent neutralization.

Congenital Zika virus (ZIKV) infection results in neurodevelopmental deficits in up to 14% of infants born to ZIKV-infected mothers. Neutralizing antibodies are a critical component of protective immunity. Here, we demonstrate that plasma IgM contributes to ZIKV immunity in pregnancy, mediating neutralization up to 3 months post-symptoms. From a ZIKV-infected pregnant woman, we isolated a pentameric ZIKV-specific IgM (DH1017.IgM) that exhibited ultrapotent ZIKV neutralization dependent on the IgM isotype. DH1017.IgM targets an envelope dimer epitope within domain II. The epitope arrangement on the virion is compatible with concurrent engagement of all ten antigen-binding sites of DH1017.IgM, a solution not available to IgG. DH1017.IgM protected mice against viremia upon lethal ZIKV challenge more efficiently than when expressed as an IgG. Our findings identify a role for antibodies of the IgM isotype in protection against ZIKV and posit DH1017.IgM as a safe and effective candidate immunotherapeutic, particularly during pregnancy.

Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody.

Antibodies with ontogenies from VH1-2 or VH1-46-germline genes dominate the broadly neutralizing response against the CD4-binding site (CD4bs) on HIV-1. Here, we define with longitudinal sampling from time-of-infection the development of a VH1-46-derived antibody lineage that matured to neutralize 90% of HIV-1 isolates. Structures of lineage antibodies CH235 (week 41 from time-of-infection, 18% breadth), CH235.9 (week 152, 77%), and CH235.12 (week 323, 90%) demonstrated the maturing epitope to focus on the conformationally invariant portion of the CD4bs. Similarities between CH235 lineage and five unrelated CD4bs lineages in epitope focusing, length-of-time to develop breadth, and extraordinary level of somatic hypermutation suggested commonalities in maturation among all CD4bs antibodies. Fortunately, the required CH235-lineage hypermutation appeared substantially guided by the intrinsic mutability of the VH1-46 gene, which closely resembled VH1-2. We integrated our CH235-lineage findings with a second broadly neutralizing lineage and HIV-1 co-evolution to suggest a vaccination strategy for inducing both lineages.

Antibody light-chain-restricted recognition of the site of immune pressure in the RV144 HIV-1 vaccine trial is phylogenetically conserved.

In HIV-1, the ability to mount antibody responses to conserved, neutralizing epitopes is critical for protection. Here we have studied the light chain usage of human and rhesus macaque antibodies targeted to a dominant region of the HIV-1 envelope second variable (V2) region involving lysine (K) 169, the site of immune pressure in the RV144 vaccine efficacy trial. We found that humans and rhesus macaques used orthologous lambda variable gene segments encoding a glutamic acid-aspartic acid (ED) motif for K169 recognition. Structure determination of an unmutated ancestor antibody demonstrated that the V2 binding site was preconfigured for ED motif-mediated recognition prior to maturation. Thus, light chain usage for recognition of the site of immune pressure in the RV144 trial is highly conserved across species. These data indicate that the HIV-1 K169-recognizing ED motif has persisted over the diversification between rhesus macaques and humans, suggesting an evolutionary advantage of this antibody recognition mode.

AisNet: A Universal Interatomic Potential Neural Network with Encoded Local Environment Features.

This paper proposes a new interatomic potential energy neural network, AisNet, which can efficiently predict atomic energies and forces covering different molecular and crystalline materials by encoding universal local environment features, such as elements and atomic positions. Inspired by the framework of SchNet, AisNet consists of an encoding module combining autoencoder with embedding, the triplet loss function and an atomic central symmetry function (ACSF), an interaction module with a periodic boundary condition (PBC), and a prediction module. In molecules, the prediction accuracy of AisNet is comparabel with SchNet on the MD17 dataset, mainly attributed to the effective capture of chemical functional groups through the interaction module. In selected metal and ceramic material datasets, the introduction of ACSF improves the overall accuracy of AisNet by an average of 16.8% for energy and 28.6% for force. Furthermore, a close relationship is found between the feature ratio (i.e., ACSF and embedding) and the force prediction errors, exhibiting similar spoon-shaped curves in the datasets of Cu and HfO2. AisNet produces highly accurate predictions in single-commponent alloys with little data, suggesting the encoding process reduces dependence on the number and richness of datasets. Especially for force prediction, AisNet exceeds SchNet by 19.8% for Al and even 81.2% higher than DeepMD on a ternary FeCrAl alloy. Capable of processing multivariate features, our model is likely to be applied to a wider range of material systems by incorporating more atomic descriptions.

Boosting with AIDSVAX B/E Enhances Env Constant Region 1 and 2 Antibody-Dependent Cellular Cytotoxicity Breadth and Potency.

Induction of protective antibodies is a critical goal of HIV-1 vaccine development. One strategy is to induce nonneutralizing antibodies (NNAbs) that kill virus-infected cells, as these antibody specificities have been implicated in slowing HIV-1 disease progression and in protection. HIV-1 Env constant region 1 and 2 (C1C2) monoclonal antibodies (MAbs) frequently mediate potent antibody-dependent cellular cytotoxicity (ADCC), making them an important vaccine target. Here, we explore the effect of delayed and repetitive boosting of RV144 vaccine recipients with AIDSVAX B/E on the C1C2-specific MAb repertoire. It was found that boosting increased clonal lineage-specific ADCC breadth and potency. A ligand crystal structure of a vaccine-induced broad and potent ADCC-mediating C1C2-specific MAb showed that it bound a highly conserved Env gp120 epitope. Thus, boosting to affinity mature these types of IgG C1C2-specific antibody responses may be one method by which to make an improved HIV vaccine with higher efficacy than that seen in the RV144 trial.IMPORTANCE Over one million people become infected with HIV-1 each year, making the development of an efficacious HIV-1 vaccine an important unmet medical need. The RV144 human HIV-1 vaccine regimen is the only HIV-1 clinical trial to date to demonstrate vaccine efficacy. An area of focus has been on identifying ways by which to improve upon RV144 vaccine efficacy. The RV305 HIV-1 vaccine regimen was a follow-up boost of RV144 vaccine recipients that occurred 6 to 8 years after the conclusion of RV144. Our study focused on the effect of delayed boosting in humans on the vaccine-induced Env constant region 1 and 2 (C1C2)-specific antibody repertoire. It was found that boosting with an HIV-1 Env vaccine increased C1C2-specific antibody-dependent cellular cytotoxicity potency and breadth.

Element Replacement Approach by Reaction with Lewis Acidic Molten Salts to Synthesize Nanolaminated MAX Phases and MXenes.

Nanolaminated materials are important because of their exceptional properties and wide range of applications. Here, we demonstrate a general approach to synthesizing a series of Zn-based MAX phases and Cl-terminated MXenes originating from the replacement reaction between the MAX phase and the late transition-metal halides. The approach is a top-down route that enables the late transitional element atom (Zn in the present case) to occupy the A site in the pre-existing MAX phase structure. Using this replacement reaction between the Zn element from molten ZnCl2 and the Al element in MAX phase precursors (Ti3AlC2, Ti2AlC, Ti2AlN, and V2AlC), novel MAX phases Ti3ZnC2, Ti2ZnC, Ti2ZnN, and V2ZnC were synthesized. When employing excess ZnCl2, Cl-terminated MXenes (such as Ti3C2Cl2 and Ti2CCl2) were derived by a subsequent exfoliation of Ti3ZnC2 and Ti2ZnC due to the strong Lewis acidity of molten ZnCl2. These results indicate that A-site element replacement in traditional MAX phases by late transition-metal halides opens the door to explore MAX phases that are not thermodynamically stable at high temperature and would be difficult to synthesize through the commonly employed powder metallurgy approach. In addition, this is the first time that exclusively Cl-terminated MXenes were obtained, and the etching effect of Lewis acid in molten salts provides a green and viable route to preparing MXenes through an HF-free chemical approach.

Hybrid Fiber Optic Sensor, Based on the Fabry⁻Perot Interference, Assisted with Fluorescent Material for the Simultaneous Measurement of Temperature and Pressure.

Herein we design a fiber sensor able to simultaneously measure the temperature and the pressure under harsh conditions, such as strong electromagnetic interference and high pressure. It is built on the basis of the fiber-optic Fabry⁻Perot (F⁻P) interference and the temperature sensitive mechanism of fluorescent materials. Both halogen lamps and light-emitting diodes (LED) are employed as the excitation light source. The reflected light from the sensor contains the low coherent information of interference cavity and the fluorescent lifetime. This information is independent due to the separate optical path and the different demodulation device. It delivers the messages of pressure and temperature, respectively. It is demonstrated that the sensor achieved pressure measurement at the range of 120⁻400 KPa at room temperature with a sensitivity of 1.5 nm/KPa. Moreover, the linearity of pressure against the cavity length variation was over 99.9%. In the meantime, a temperature measurement in the range of 25⁻80 °C, with a sensitivity of 0.0048 ms/°C, was obtained. These experimental results evince that this kind of sensor has a simple configuration, low-cost, and easy fabrication. As such, it can be particularly applied to many fields.

HIV DNA-Adenovirus Multiclade Envelope Vaccine Induces gp41 Antibody Immunodominance in Rhesus Macaques.

Dominant antibody responses in vaccinees who received the HIV-1 multiclade (A, B, and C) envelope (Env) DNA/recombinant adenovirus virus type 5 (rAd5) vaccine studied in HIV-1 Vaccine Trials Network (HVTN) efficacy trial 505 (HVTN 505) targeted Env gp41 and cross-reacted with microbial antigens. In this study, we asked if the DNA/rAd5 vaccine induced a similar antibody response in rhesus macaques (RMs), which are commonly used as an animal model for human HIV-1 infections and for testing candidate HIV-1 vaccines. We also asked if gp41 immunodominance could be avoided by immunization of neonatal RMs during the early stages of microbial colonization. We found that the DNA/rAd5 vaccine elicited a higher frequency of gp41-reactive memory B cells than gp120-memory B cells in adult and neonatal RMs. Analysis of the vaccine-induced Env-reactive B cell repertoire revealed that the majority of HIV-1 Env-reactive antibodies in both adult and neonatal RMs were targeted to gp41. Interestingly, a subset of gp41-reactive antibodies isolated from RMs cross-reacted with host antigens, including autologous intestinal microbiota. Thus, gp41-containing DNA/rAd5 vaccine induced dominant gp41-microbiota cross-reactive antibodies derived from blood memory B cells in RMs as observed in the HVTN 505 vaccine efficacy trial. These data demonstrated that RMs can be used to investigate gp41 immunodominance in candidate HIV-1 vaccines. Moreover, colonization of neonatal RMs occurred within the first week of life, and immunization of neonatal RMs during this time also induced a dominant gp41-reactive antibody response.IMPORTANCE Our results are critical to current work in the HIV-1 vaccine field evaluating the phenomenon of gp41 immunodominance induced by HIV-1 Env gp140 in RMs and humans. Our data demonstrate that RMs are an appropriate animal model to study this phenomenon and to determine the immunogenicity in new HIV-1 Env trimer vaccine designs. The demonstration of gp41 immunodominance in memory B cells of both adult and neonatal RMs indicated that early vaccination could not overcome gp41 dominant responses.

High-Speed Device-Independent Quantum Random Number Generation without a Detection Loophole.

Quantum mechanics provides the means of generating genuine randomness that is impossible with deterministic classical processes. Remarkably, the unpredictability of randomness can be certified in a manner that is independent of implementation devices. Here, we present an experimental study of device-independent quantum random number generation based on a detection-loophole-free Bell test with entangled photons. In the randomness analysis, without the independent identical distribution assumption, we consider the worst case scenario that the adversary launches the most powerful attacks against the quantum adversary. After considering statistical fluctuations and applying an 80 Gb×45.6 Mb Toeplitz matrix hashing, we achieve a final random bit rate of 114 bits/s, with a failure probability less than 10^{-5}. This marks a critical step towards realistic applications in cryptography and fundamental physics tests.

Antibodies Elicited by Multiple Envelope Glycoprotein Immunogens in Primates Neutralize Primary Human Immunodeficiency Viruses (HIV-1) Sensitized by CD4-Mimetic Compounds.

UNLABELLED: The human immunodeficiency virus (HIV-1) envelope glycoproteins (Env) mediate virus entry through a series of complex conformational changes triggered by binding to the receptors CD4 and CCR5/CXCR4. Broadly neutralizing antibodies that recognize conserved Env epitopes are thought to be an important component of a protective immune response. However, to date, HIV-1 Env immunogens that elicit broadly neutralizing antibodies have not been identified, creating hurdles for vaccine development. Small-molecule CD4-mimetic compounds engage the CD4-binding pocket on the gp120 exterior Env and induce Env conformations that are highly sensitive to neutralization by antibodies, including antibodies directed against the conserved Env region that interacts with CCR5/CXCR4. Here, we show that CD4-mimetic compounds sensitize primary HIV-1 to neutralization by antibodies that can be elicited in monkeys and humans within 6 months by several Env vaccine candidates, including gp120 monomers. Monoclonal antibodies directed against the gp120 V2 and V3 variable regions were isolated from the immunized monkeys and humans; these monoclonal antibodies neutralized a primary HIV-1 only when the virus was sensitized by a CD4-mimetic compound. Thus, in addition to their direct antiviral effect, CD4-mimetic compounds dramatically enhance the HIV-1-neutralizing activity of antibodies that can be elicited with currently available immunogens. Used as components of microbicides, the CD4-mimetic compounds might increase the protective efficacy of HIV-1 vaccines. IMPORTANCE: Preventing HIV-1 transmission is a high priority for global health. Eliciting antibodies that can neutralize transmitted strains of HIV-1 is difficult, creating problems for the development of an effective vaccine. We found that small-molecule CD4-mimetic compounds sensitize HIV-1 to antibodies that can be elicited in vaccinated humans and monkeys. These results suggest an approach to prevent HIV-1 sexual transmission in which a virus-sensitizing microbicide is combined with a vaccine.

Two-Hierarchy Entanglement Swapping for a Linear Optical Quantum Repeater.

Quantum repeaters play a significant role in achieving long-distance quantum communication. In the past decades, tremendous effort has been devoted towards constructing a quantum repeater. As one of the crucial elements, entanglement has been created in different memory systems via entanglement swapping. The realization of j-hierarchy entanglement swapping, i.e., connecting quantum memory and further extending the communication distance, is important for implementing a practical quantum repeater. Here, we report the first demonstration of a fault-tolerant two-hierarchy entanglement swapping with linear optics using parametric down-conversion sources. In the experiment, the dominant or most probable noise terms in the one-hierarchy entanglement swapping, which is on the same order of magnitude as the desired state and prevents further entanglement connections, are automatically washed out by a proper design of the detection setting, and the communication distance can be extended. Given suitable quantum memory, our techniques can be directly applied to implementing an atomic ensemble based quantum repeater, and are of significant importance in the scalable quantum information processing.

Ab Initio Studies on the Clathrate Hydrates of Some Nitrogen- and Sulfur-Containing Gases.

Ab initio calculations are performed to investigate the host-guest interactions and multiple occupancies of some sulfur- (H2S, CS2) and nitrogen-containing (N2, NO, and NH3) molecules in dodecahedral, tetrakaidecahedral, and hexakaidecahedral water cages in this work. Five functionals in the framework of density functional theory are compared, and the M06-2X method appears to be the best to predict the binding energies as well as the geometries. Results show that N2 and NO molecules are more stable in the 51264 cage, while NH3 and H2S prefer to stabilize in the 51262 cage. This suggests that the sI hydrates of NH3 and H2S exhibit higher stability than the sII structures and that sII NO hydrate is more stable than sI NO hydrate. N2 is found to be more stable in type II structure with single occupancy and to form type I hydrate with multiple occupancy, which is consistent with the experimental observations. As to the guest molecule CS2, it may undergo severe structural deformation in the 512 and 51262 cage. For multiple occupancies, the 512, 51262, and 51264 water cages can trap up to two N2 molecules, and the 51264 water cage can accommodate two H2S molecules. This work is expected to provide new insight into the formation mechanism of clathrate hydrates for atmospherically important molecules.

Secret Sharing of a Quantum State.

Secret sharing of a quantum state, or quantum secret sharing, in which a dealer wants to share a certain amount of quantum information with a few players, has wide applications in quantum information. The critical criterion in a threshold secret sharing scheme is confidentiality: with less than the designated number of players, no information can be recovered. Furthermore, in a quantum scenario, one additional critical criterion exists: the capability of sharing entangled and unknown quantum information. Here, by employing a six-photon entangled state, we demonstrate a quantum threshold scheme, where the shared quantum secrecy can be efficiently reconstructed with a state fidelity as high as 93%. By observing that any one or two parties cannot recover the secrecy, we show that our scheme meets the confidentiality criterion. Meanwhile, we also demonstrate that entangled quantum information can be shared and recovered via our setting, which shows that our implemented scheme is fully quantum. Moreover, our experimental setup can be treated as a decoding circuit of the five-qubit quantum error-correcting code with two erasure errors.

Experimental Ten-Photon Entanglement.

We report the first experimental demonstration of quantum entanglement among ten spatially separated single photons. A near-optimal entangled photon-pair source was developed with simultaneously a source brightness of ∼12 MHz/W, a collection efficiency of ∼70%, and an indistinguishability of ∼91% between independent photons, which was used for a step-by-step engineering of multiphoton entanglement. Under a pump power of 0.57 W, the ten-photon count rate was increased by about 2 orders of magnitude compared to previous experiments, while maintaining a state fidelity sufficiently high for proving the genuine ten-particle entanglement. Our work created a state-of-the-art platform for multiphoton experiments, and enabled technologies for challenging optical quantum information tasks, such as the realization of Shor's error correction code and high-efficiency scattershot boson sampling.

[Low-power Wireless Micro Ambulatory Electrocardiogram Node].

Ambulatory electrocardiogram (ECG) monitoring can effectively reduce the risk and death rate of patients with cardiovascular diseases (CVDs). The Body Sensor Network (BSN) based ECG monitoring is a new and efficien method to protect the CVDs patients. To meet the challenges of miniaturization, low power and high signal quality of the node, we proposed a novel 50 mmX 50 mmX 10 mm, 30 g wireless ECG node, which includes the single-chip an alog front-end AD8232, ultra-low power microprocessor MSP430F1611 and Bluetooth module HM-11. The ECG signal quality is guaranteed by the on-line digital filtering. The difference threshold algorithm results in accuracy of R-wave detection and heart rate. Experiments were carried out to test the node and the results showed that the pro posed node reached the design target, and it has great potential in application of wireless ECG monitoring.

Combinatorial library-based profiling of the antibody response against hepatitis C virus in humans.

The antibody response plays a crucial role against hepatitis C virus (HCV) infection, and our understanding of this intricate progress in vivo is far from complete. We previously reported a novel and robust technique based on a large combinatorial viral antigen library displayed on the surface of the yeast Saccharomyces cerevisiae, allowing comprehensive profiling of polyclonal antibody responses in vivo in both qualitative and quantitative terms. Here, we report the generation and application of a combinatorial library of HCV strain JFH1 envelope glycoprotein to profile the antibody response in four HCV chronically infected individuals. By systematic analysis of the location and frequency of antigenic fragments along the JFH1 envelope glycoprotein, we showed that the major binding antibody response was targeted to E2 (80.9-99.8 %), whilst that against E1 was relatively small (0.3-19.0 %). A total of five major antigenic domains (D1-D5) were identified: one was within E1 and an additional four within E2, despite substantial variability among the different individuals. However, serum absorption with the yeast clones containing the antigenic domain D1 resulted in more reduction in neutralizing antibody activity against pseudotyped HCV than those in E2, suggesting that E1 contains additional neutralizing epitopes. Our results have provided additional insights into the HCV-specific antibody response in humans and should assist in a better understanding of protective antibody immunity and in guiding the development of effective vaccines and therapeutics against HCV infection.

New insight into the helium-induced damage in MAX phase Ti3AlC2 by first-principles studies.

In the present work, the behavior of He in the MAX phase Ti3AlC2 material is investigated using first-principle methods. It is found that, according to the predicted formation energies, a single He atom favors residing near the Al plane in Ti3AlC2. The results also show that Al vacancies are better able to trap He atoms than either Ti or C vacancies. The formation energies for the secondary vacancy defects near an Al vacancy or a C vacancy are strongly influenced by He impurity content. According to the present results, the existence of trapped He atoms in primary Al vacancy can promote secondary vacancy formation and the He bubble trapped by Al vacancies has a higher tendency to grow in the Al plane of Ti3AlC2. The diffusion of He in Ti3AlC2 is also investigated. The energy barriers are approximately 2.980 eV and 0.294 eV along the c-axis and in the ab plane, respectively, which means that He atoms exhibit faster migration parallel to the Al plane. Hence, the formation of platelet-like bubbles nucleated from the Al vacancies is favored both energetically and kinetically. Our calculations also show that the conventional spherical bubbles may be originated from He atoms trapped by C vacancies. Taken together, these results are able to explain the observed formation of bubbles in various shapes in recent experiments. This study is expected to provide new insight into the behaviors of MAX phases under irradiation from electronic structure level in order to improve the design of MAX phase based materials.

Implementation of a measurement-device-independent entanglement witness.

Entanglement, the essential resource in quantum information processing, should be witnessed in many tasks such as quantum computing and quantum communication. The conventional entanglement witness method, relying on an idealized implementation of measurements, could wrongly conclude a separable state to be entangled due to imperfect detections. Inspired by the idea of a time-shift attack, we construct an attack on the conventional entanglement witness process and demonstrate that a separable state can be falsely identified to be entangled. To close such detection loopholes, based on a recently proposed measurement-device-independent entanglement witness method, we design and experimentally demonstrate a measurement-device-independent entanglement witness for a variety of two-qubit states. By the new scheme, we show that an entanglement witness can be realized without detection loopholes.

Structural, Electronic, and Mechanical Properties of Zr2SeB and Zr2SeN from First-Principle Investigations.

MAX phases have exhibited diverse physical properties, inspiring their promising applications in several important research fields. The introduction of a chalcogen atom into a phase of MAX has further facilitated the modulation of their physical properties and the extension of MAX family diversity. The physical characteristics of the novel chalcogen-containing MAX 211 phase Zr2SeB and Zr2SeN have been systematically investigated. The present investigation is conducted from a multi-faceted perspective that encompasses the stability, electronic structure, and mechanical properties of the system, via the employment of the first-principles density functional theory methodology. By replacing C with B/N in the chalcogen-containing MAX phase, it has been shown that their corresponding mechanical properties are appropriately tuned, which may offer a way to design novel MAX phase materials with enriched properties. In order to assess the dynamical and mechanical stability of the systems under investigation, a thorough evaluation has been carried out based on the analysis of phonon dispersions and elastic constants conditions. The predicted results reveal a strong interaction between zirconium and boron or nitrogen within the structures of Zr2SeB and Zr2SeN. The calculated band structures and electronic density of states for Zr2SeB and Zr2SeN demonstrate their metallic nature and anisotropic conductivity. The theoretically estimated Pugh and Poisson ratios imply that these phases are characterized by brittleness.

Two-Dimensional Half-Metallic and Semiconducting Lanthanide-Based MXenes.

As a large family of two-dimensional materials, MXenes have attracted intensive attention in recent years. For more functional applications, it is of great significance to determine new MXene members. Here, we theoretically expand the M elements of MXenes to the lanthanide series. Based on density functional theory calculations, the bare lanthanide-based carbides M2C (M = Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, and Yb) and the corresponding fluorine- and hydroxyl-terminated configurations are investigated. Most of the fluorine- and hydroxyl-terminated MXenes investigated are half-metals. Specifically, in the half-metallic Eu2CF2, the spin-down states show a band gap larger than 2 eV, implying this configuration's potential applications in spin generation and injection. Both Gd2CT2 (T = F and OH) are magnetic semiconductors. The former shows an indirect band gap of 1.38 eV, while the latter presents a direct one of 0.882 eV. These two configurations also show large magnetic moments higher than 13.7 µB per unit cell. All the hydroxyl-terminated MXene members show relatively low work functions, with the lowest value of 1.46 eV determined in Tm2C(OH)2. These predicted electronic properties imply that the lanthanide-based MXenes could have potential applications in spintronics, information storage, near-infrared detectors, field effect transistors, and field emitter cathodes.