Deep multi-view contrastive learning for cancer subtype identification.

Cancer heterogeneity has posed great challenges in exploring precise therapeutic strategies for cancer treatment. The identification of cancer subtypes aims to detect patients with distinct molecular profiles and thus could provide new clues on effective clinical therapies. While great efforts have been made, it remains challenging to develop powerful computational methods that can efficiently integrate multi-omics datasets for the task. In this paper, we propose a novel self-supervised learning model called Deep Multi-view Contrastive Learning (DMCL) for cancer subtype identification. Specifically, by incorporating the reconstruction loss, contrastive loss and clustering loss into a unified framework, our model simultaneously encodes the sample discriminative information into the extracted feature representations and well preserves the sample cluster structures in the embedded space. Moreover, DMCL is an end-to-end framework where the cancer subtypes could be directly obtained from the model outputs. We compare DMCL with eight alternatives ranging from classic cancer subtype identification methods to recently developed state-of-the-art systems on 10 widely used cancer multi-omics datasets as well as an integrated dataset, and the experimental results validate the superior performance of our method. We further conduct a case study on liver cancer and the analysis results indicate that different subtypes might have different responses to the selected chemotherapeutic drugs.

Importance of Spin Channels from Radical-Radical Reactions in Hydrogen-Oxygen Combustion Mechanisms at High Temperatures.

Radical-radical reactions can generate two channels with high and low spins. In this work, ten radical-radical reactions with different spin channels and four radical-molecule reactions in hydrogen-oxygen combustion were systematically investigated from a theoretical perspective. The potential energy surface (PES) of radical-radical reactions reveals that the high- and low-spin states of the reactant are energetically degenerate and the two channels are energetically feasible. The difference in rate constants between the high- and low-spin channels gradually decreases as the temperature increases. Then, the kinetic parameters of the 14 bimolecular reactions in the hydrogen-oxygen mechanism of the University of California, San Diego (UCSD), were replaced to simulate the ignition delay time and laminar flame speed. The simulation results agree well with the available experimental findings, indicating the necessity of considering both high- and low-spin channels for kinetic simulation.

Universal Quantum Optimization with Cold Atoms in an Optical Cavity.

Cold atoms in an optical cavity have been widely used for quantum simulations of many-body physics, where the quantum control capability has been advancing rapidly in recent years. Here, we show the atom cavity system is universal for quantum optimization with arbitrary connectivity. We consider a single-mode cavity and develop a Raman coupling scheme by which the engineered quantum Hamiltonian for atoms directly encodes number partition problems. The programmability is introduced by placing the atoms at different positions in the cavity with optical tweezers. The number partition problem solution is encoded in the ground state of atomic qubits coupled through a photonic cavity mode, which can be reached by adiabatic quantum computing. We construct an explicit mapping for the 3-SAT and vertex cover problems to be efficiently encoded by the cavity system, which costs linear overhead in the number of atomic qubits. The atom cavity encoding is further extended to quadratic unconstrained binary optimization problems. The encoding protocol is optimal in the cost of atom number scaling with the number of binary degrees of freedom of the computation problem. Our theory implies the atom cavity system is a promising quantum optimization platform searching for practical quantum advantage.

Recovery of Li2CO3 from Spent LiFePO4 by Using a Novel Impurity Elimination Process.

The large-scale implementations of lithium iron phosphate (LFP) batteries for energy storage systems have been gaining attention around the world due to their quality of high technological maturity and flexible configuration. Unfortunately, the exponential production of LFP batteries is accompanied by an annual accumulation of spent batteries and a premature consumption of the lithium resource. Recycling souring critical battery materials such as Li2CO3 is essential to reduce the supply chain risk and achieve net carbon neutrality goals. During the recovery of Li2CO3, impurity removal is the most crucial step in the hydrometallurgy process of spent LiFePO4, which determines the purity of Li2CO3. By investigating and comparing the results of impurity elimination from the purified Li+-containing liquids with strong and weak alkalis under identical pH conditions, respectively, a strategy based on an alkali mixture has been proposed. The purified Li+-containing liquid was, thereafter, concentrated and sodium carbonate was added in order to precipitate Li2CO3. As a result, a high purity Li2CO3 (99.51%) of battery grade was obtained. LiFePO4 prepared with the recovered Li2CO3 and FePO4 as raw materials also displayed a comparative high capacity and stable cycle performance to the commercial product and further verified the electrochemical activity of the recovered materials.

Quantum gas microscope assisted with T-shape vacuum viewports.

A quantum gas microscope plays an important role in cold-atom experiments, which provides a high-resolution imaging of the spatial distributions of cold atoms. Here we design, build and calibrate an integrated microscope for quantum gases with all the optical components fixed outside the vacuum chamber. It provides large numerical aperture (NA) of 0.75, as well as good optical access from side for atom loading in cold-atom experiments due to long working distance (7 mm fused silica+6 mm vacuum) of the microscope objective. We make a special design of the vacuum viewport with a T-shape window, to suppress the window flatness distortion introduced by the metal-glass binding process, and protect the high-resolution imaging from distortions due to unflattened window. The achieved Strehl ratio is 0.9204 using scanning-near-field microscopy (SNOM) fiber coupling incoherent light as point light source.

Preparation of the Spin-Mott State: A Spinful Mott Insulator of Repulsively Bound Pairs.

We observe and study a special ground state of bosons with two spin states in an optical lattice: the spin-Mott insulator, a state that consists of repulsively bound pairs that is insulating for both spin and charge transport. Because of the pairing gap created by the interaction anisotropy, it can be prepared with low entropy and can serve as a starting point for adiabatic state preparation. We find that the stability of the spin-Mott state depends on the pairing energy, and observe two qualitatively different decay regimes, one of which exhibits protection by the gap.

The transplantation of rapamycin-treated senescent human mesenchymal stem cells with enhanced proangiogenic activity promotes neovascularization and ischemic limb salvage in mice.

Few therapies can reverse the proangiogenic activity of senescent mesenchymal stromal/stem cells (MSCs). In this study, we investigated the effects of rapamycin on the proangiogenic ability of senescent human umbilical cord MSCs (UCMSCs). An in vitro replicative senescent cell model was established in cultured UCMSCs. We found that late passage (P25 or later) UCMSCs (LP-UCMSCs) exhibited impaired proangiogenic abilities. Treatment of P25 UCMSCs with rapamycin (900 nM) reversed the senescent phenotype and notably enhanced the proangiogenic activity of senescent UCMSCs. In a nude mouse model of hindlimb ischemia, intramuscular injection of rapamycin-treated P25 UCMSCs into the ischemic limb significantly promoted neovascularization and ischemic limb salvage. We further analyzed the changes in the expression of angiogenesis-associated genes in rapamycin-primed MSCs and found higher expression of several genes related to angiogenesis, such as VEGFR2 and CTGF/CCN2, in primed cells than in unprimed MSCs. Taken together, our data demonstrate that rapamycin is a potential drug to restore the proangiogenic activity of senescent MSCs, which is of importance in treating ischemic diseases and tissue engineering.

Avatrombopag improves thrombocytopenia in MYH9-related disorder following eltrombopag treatment failure.

MYH9-related disorder (MYH9-RD) is autosomal dominant thrombocytopenia caused by mutations in the MYH9 gene, which codes for the non-muscle myosin-IIA heavy chain. We present a case of a 24-year-old Chinese man with MYH9-RD who was initially misdiagnosed with immune thrombocytopenia. Whole-exome sequencing and Sanger sequencing revealed a novel missense mutation in the MYH9 gene at the position of c.4550 G > T (p.G1517V) in exon 32. The same phenotype was observed in the proband, his mother, and his brother, in addition to macrothrombocytopenia and Dohle-like bodies in neutrophil granulocytes without non-hematologic manifestations. Following failed treatment with eltrombopag, avatrombopag, which was not mentioned before in the MYH9-RD treatment, was administered to the patient, and thrombocytopenia improved. In this case report, we present a novel pathogenic mutation and show the potential of avatrombopag for temporarily increasing the platelet count in patients with MYH9-RD.

Observation of Many-Body Quantum Phase Transitions beyond the Kibble-Zurek Mechanism.

Quantum critical behavior of many-body phase transitions is one of the most fascinating yet challenging questions in quantum physics. Here, we improved the band-mapping method to investigate the quantum phase transition from superfluid to Mott insulators, and we observed the critical behaviors of quantum phase transitions in both the dynamical steady-state-relaxation region and the phase-oscillation region. Based on various observables, two different values for the same quantum critical parameter are observed. This result is beyond a universal-scaling-law description of quantum phase transitions known as the Kibble-Zurek mechanism, and suggests that multiple quantum critical mechanisms are competing in many-body quantum phase transition experiments in inhomogeneous systems.

Partially Nondestructive Continuous Detection of Individual Traveling Optical Photons.

We report the continuous and partially nondestructive measurement of optical photons. For a weak light pulse traveling through a slow-light optical medium (signal), the associated atomic-excitation component is detected by another light beam (probe) with the aid of an optical cavity. We observe strong correlations of g_{sp}^{(2)}=4.4(5) between the transmitted signal and probe photons. The observed (intrinsic) conditional nondestructive quantum efficiency ranges between 13% and 1% (65% and 5%) for a signal transmission range of 2% to 35%, at a typical time resolution of 2.5 µs. The maximal observed (intrinsic) device nondestructive quantum efficiency, defined as the product of the conditional nondestructive quantum efficiency and the signal transmission, is 0.5% (2.4%). The normalized cross-correlation function violates the Cauchy-Schwarz inequality, confirming the nonclassical character of the correlations.

Coherence Times of Bose-Einstein Condensates beyond the Shot-Noise Limit via Superfluid Shielding.

We demonstrate a new way to extend the coherence time of separated Bose-Einstein condensates that involves immersion into a superfluid bath. When both the system and the bath have similar scattering lengths, immersion in a superfluid bath cancels out inhomogeneous potentials either imposed by external fields or inherent in density fluctuations due to atomic shot noise. This effect, which we call superfluid shielding, allows for coherence lifetimes beyond the projection noise limit. We probe the coherence between separated condensates in different sites of an optical lattice by monitoring the contrast and decay of Bloch oscillations. Our technique demonstrates a new way that interactions can improve the performance of quantum devices.

Carving Complex Many-Atom Entangled States by Single-Photon Detection.

We propose a versatile and efficient method to generate a broad class of complex entangled states of many atoms via the detection of a single photon. For an atomic ensemble contained in a strongly coupled optical cavity illuminated by weak single- or multifrequency light, the atom-light interaction entangles the frequency spectrum of a transmitted photon with the collective spin of the atomic ensemble. Simple time-resolved detection of the transmitted photon then projects the atomic ensemble into a desired pure entangled state. This method can be implemented with existing technology, yields high success probability per trial, and can generate complex entangled states such as mesoscopic superposition states of coherent spin states with high fidelity.

Cross modulation of two laser beams at the individual-photon level.

Deterministic photon-photon interactions are a long-standing goal in optical science. Using an atomic ensemble inside a cavity, we demonstrate the mutual cross modulation of two continuous light beams at the level of individual photons. The originally uncorrelated beams derived from independent lasers become anticorrelated, as evidenced by an equal-time cross-correlation function g^{(2)}=0.89(1), showing that one photon in one beam extinguishes a photon in the other beam with a probability of 11(1)%. With further technical improvements, our approach should enable the nondestructive continuous detection of traveling optical photons.

Discovery of glycosyltransferases using carbohydrate arrays and mass spectrometry.

Glycosyltransferases catalyze the reaction between an activated sugar donor and an acceptor to form a new glycosidic linkage. Glycosyltransferases are responsible for the assembly of oligosaccharides in vivo and are also important for the in vitro synthesis of these biomolecules. However, the functional identification and characterization of new glycosyltransferases is difficult and tedious. This paper describes an approach that combines arrays of reactions on an immobilized array of acceptors with an analysis by mass spectrometry to screen putative glycosyltransferases. A total of 14,280 combinations of a glycosyltransferase, an acceptor and a donor in four buffer conditions were screened, leading to the identification and characterization of four new glycosyltransferases. This work is notable because it provides a label-free method for the rapid functional annotation of putative enzymes.

Targeting Senescent Alveolar Epithelial Cells Using Engineered Mesenchymal Stem Cell-Derived Extracellular Vesicles To Treat Pulmonary Fibrosis.

Type 2 alveolar epithelial cell (AEC2) senescence is crucial to the pathogenesis of pulmonary fibrosis (PF). The nicotinamide adenine dinucleotide (NAD+)-consuming enzyme cluster of differentiation 38 (CD38) is a marker of senescent cells and is highly expressed in AEC2s of patients with PF, thus rendering it a potential treatment target. Umbilical cord mesenchymal stem cell (MSC)-derived extracellular vesicles (MSC-EVs) have emerged as a cell-free treatment with clinical application prospects in antiaging and antifibrosis treatments. Herein, we constructed CD38 antigen receptor membrane-modified MSC-EVs (CD38-ARM-MSC-EVs) by transfecting MSCs with a lentivirus loaded with a CD38 antigen receptor-CD8 transmembrane fragment fusion plasmid to target AEC2s and alleviate PF. Compared with MSC-EVs, the CD38-ARM-MSC-EVs engineered in this study showed a higher expression of the CD38 antigen receptor and antifibrotic miRNAs and targeted senescent AEC2s cells highly expressing CD38 in vitro and in naturally aged mouse models after intraperitoneal administration. CD38-ARM-MSC-EVs effectively restored the NAD+ levels, reversed the epithelial-mesenchymal transition phenotype, and rejuvenated senescent A549 cells in vitro, thereby mitigating multiple age-associated phenotypes and alleviating PF in aged mice. Thus, this study provides a technology to engineer MSC-EVs and support our CD38-ARM-MSC-EVs to be developed as promising agents with high clinical potential against PF.

Adaptability of the semi-invariant natural killer T-cell receptor towards structurally diverse CD1d-restricted ligands.

The semi-invariant natural killer (NK) T-cell receptor (NKTcr) recognises structurally diverse glycolipid antigens presented by the monomorphic CD1d molecule. While the alpha-chain of the NKTcr is invariant, the beta-chain is more diverse, but how this diversity enables the NKTcr to recognise diverse antigens, such as an alpha-linked monosaccharide (alpha-galactosylceramide and alpha-galactosyldiacylglycerol) and the beta-linked trisaccharide (isoglobotriaosylceramide), is unclear. We demonstrate here that NKTcrs, which varied in their beta-chain usage, recognised diverse glycolipid antigens with a similar binding mode on CD1d. Nevertheless, the NKTcrs recognised distinct epitopic sites within these antigens, including alpha-galactosylceramide, the structurally similar alpha-galactosyldiacylglycerol and the very distinct isoglobotriaosylceramide. We also show that the relative roles of the CDR loops within the NKTcr beta-chain varied as a function of the antigen. Thus, while NKTcrs characteristically use a conserved docking mode, the NKTcr beta-chain allows these cells to recognise unique aspects of structurally diverse CD1d-restricted ligands.

COVID-19 in China and the US: Differences in Hospital Admission Co-Variates and Outcomes.

(1) Background: Although there are extensive data on admission co-variates and outcomes of persons with coronavirus infectious disease-2019 (COVID-19) at diverse geographic sites, there are few, if any, subject-level comparisons between sites in regions and countries. We investigated differences in hospital admission co-variates and outcomes of hospitalized people with COVID-19 between Wuhan City, China and the New York City region, USA. (2) Methods: We retrospectively analyzed clinical data on 1859 hospitalized subjects with COVID-19 in Wuhan City, China, from 20 January to 4 April 2020. Data on 5700 hospitalized subjects with COVID-19 in the New York City region, USA, from 1 March to 4 April 2020 were extracted from an article by Richardson et al. Hospital admission co-variates (epidemiological, demographic, and laboratory co-variates) and outcomes (rate of intensive care unit [ICU] admission, invasive mechanical ventilation [IMV], major organ failure and death, and length of hospital stay) were compared between the cohorts. (3) Results: Wuhan subjects were younger, more likely female, less likely to have co-morbidities and fever, more likely to have a blood lymphocyte concentration > 1 × 109/L, and less likely to have abnormal liver and cardiac function tests compared with New York subjects. There were outcomes data on all Wuhan subjects and 2634 New York subjects. Wuhan subjects had higher blood nadir median lymphocyte concentrations and longer hospitalizations, and were less likely to receive IMV, ICU hospitalization, and interventions for kidney failure. Amongst subjects not receiving IMV, those in Wuhan were less likely to die compared with New York subjects. In contrast, risk of death was similar in subjects receiving IMV at both sites. (4) Conclusions: We found different hospital admission co-variates and outcomes between hospitalized persons with COVID-19 between Wuhan City and the New York region, which should be useful developing a comprehensive global understanding of the SARS-CoV-2 pandemic and COVID-19.

Changes in the medical-seeking pattern and daily behavior of hematopoietic stem-cell transplant recipients during the COVID-19 epidemic: An online survey in Hubei Province, China.

Background: To curb the spread of the coronavirus disease 2019 (COVID-19) epidemic, the Chinese government shut down Wuhan city from January 23rd to April 8th, 2020. The COVID-19 epidemic not only leads to widespread illness but also affects the diagnosis and treatment of hematopoietic stem-cell transplant (HSCT) recipients. Objective: To investigate the medical-seeking pattern and daily behavior changes in Hubei Province during the COVID-19 epidemic in Hubei Province during the lockdown. Methods: We conducted a multicenter, cross-sectional, web-based investigation among 325 HSCT recipients by online questionnaires in Hubei Province during the COVID-19 epidemic. Results: A total of 145 complete responses were collected both before and during the epidemic questionnaires. The participants from pre-epidemic group preferred to go to hospital (68.29%) when they experienced influenza-like symptoms. The majority of the patients elected to take oral drugs by themselves (40%) or consulted their attending physicians online or by telephone during the lockdown (23.33%). 64.83% had difficulties in purchasing drugs during the lockdown, which was significantly higher than the proportion of the pre-epidemic group (24.83%) (P < 0.05). The participants preferred to purchase drugs online (23.40%) and decrease or withdraw drugs (18.09%) during the epidemic. The number of participants received regular re-examinations during the epidemic decreased sharply. The proportion of wearing masks and isolating themselves at home increased significantly during the epidemic. No statistic difference was observed in the incidence of graft-versus-host disease (GVHD)complications in participants between the during the epidemic group and the pre-epidemic group. In our study, six patients were confirmed to have COVID-19, and half of them died due to COVID-19-related complications. Conclusion: The medical-seeking pattern and daily behavior of HSCT recipients changed during the lockdown; the methods of self-protection, online consultation and drug delivery can help patients receive necessary follow-up and reduce the occurrence of COVID-19.

Probing quantum many-body correlations by universal ramping dynamics.

Ramping a physical parameter is one of the most common experimental protocols in studying a quantum system, and ramping dynamics has been widely used in preparing a quantum state and probing physical properties. Here, we present a novel method of probing quantum many-body correlation by ramping dynamics. We ramp a Hamiltonian parameter to the same target value from different initial values and with different velocities, and we show that the first-order correction on the finite ramping velocity is universal and path-independent, revealing a novel quantum many-body correlation function of the equilibrium phases at the target values. We term this method as the non-adiabatic linear response since this is the leading order correction beyond the adiabatic limit. We demonstrate this method experimentally by studying the Bose-Hubbard model with ultracold atoms in three-dimensional optical lattices. Unlike the conventional linear response that reveals whether the quasi-particle dispersion of a quantum phase is gapped or gapless, this probe is more sensitive to whether the quasi-particle lifetime is long enough such that the quantum phase possesses a well-defined quasi-particle description. In the Bose-Hubbard model, this non-adiabatic linear response is significant in the quantum critical regime where well-defined quasi-particles are absent. And in contrast, this response is vanishingly small in both superfluid and Mott insulators which possess well-defined quasi-particles. Because our proposal uses the most common experimental protocol, we envision that our method can find broad applications in probing various quantum systems.

Combining carbochips and mass spectrometry to study the donor specificity for the Neisseria meningitidis ß1,3-N-acetylglucosaminyltransferase LgtA.

A library of 11 UDP-N-acetylglucosamine analogs were rapidly screened for their activities as donors for the Neisseria meningitidis ß1,3-N-acetylglucosaminyltransferase (LgtA) by direct on-chip reaction and detection with SAMDI-TOF mass spectrometry. Six of the analogs were active in this assay and were analyzed by SAMDI to characterize the kinetics toward LgtA. The analysis revealed that substitutions on C-2, C-4, and C-6 affect the activity of the donors, with bulky groups at these positions decreasing affinity of the donors for the enzyme, and also revealed that activity is strongly affected by the stereochemistry at C-3, but not C-4, of the donor. The study is also significant because it demonstrates that SAMDI can be used to both profile glycosyltransferase activities and to provide a quantitative assessment of enzyme activity.