Multiple Dendritic Cell Populations Activate CD4+ T Cells after Viral Stimulation

Dendritic cells (DC) are a heterogeneous cell population that bridge the innate and adaptive immune systems. CD8α DC play a prominent, and sometimes exclusive, role in driving amplification of CD8+ T cells during a viral infection. Whether this reliance on a single subset of DC also applies for CD4+ T cell activation is unknown. We used a direct ex vivo antigen presentation assay to probe the capacity of flow cytometrically purified DC populations to drive amplification of CD4+ and CD8+ T cells following infection with influenza virus by different routes. This study examined the contributions of non-CD8α DC populations in the amplification of CD8+ and CD4+ T cells in cutaneous and systemic influenza viral infections. We confirmed that in vivo, effective immune responses for CD8+ T cells are dominated by presentation of antigen by CD8α DC but can involve non-CD8α DC. In contrast, CD4+ T cell responses relied more heavily on the contributions of dermal DC migrating from peripheral lymphoid tissues following cutaneous infection, and CD4 DC in the spleen after systemic infection. CD4+ T cell priming by DC subsets that is dependent upon the route of administration raises the possibility that vaccination approaches could be tailored to prime helper T cell immunity

MIA-Prognosis: A Deep Learning Framework to Predict Therapy Response

Predicting clinical outcome is remarkably important but challenging. Research efforts have been paid on seeking significant biomarkers associated with the therapy response or/and patient survival. However, these biomarkers are generally costly and invasive, and possibly dissatifactory for novel therapy. On the other hand, multi-modal, heterogeneous, unaligned temporal data is continuously generated in clinical practice. This paper aims at a unified deep learning approach to predict patient prognosis and therapy response, with easily accessible data, e.g., radiographics, laboratory and clinical information. Prior arts focus on modeling single data modality, or ignore the temporal changes. Importantly, the clinical time series is asynchronous in practice, i.e., recorded with irregular intervals. In this study, we formalize the prognosis modeling as a multi-modal asynchronous time series classification task, and propose a MIA-Prognosis framework with Measurement, Intervention and Assessment (MIA) information to predict therapy response, where a Simple Temporal Attention (SimTA) module is developed to process the asynchronous time series. Experiments on synthetic dataset validate the superiory of SimTA over standard RNN-based approaches. Furthermore, we experiment the proposed method on an in-house, retrospective dataset of real-world non-small cell lung cancer patients under anti-PD-1 immunotherapy. The proposed method achieves promising performance on predicting the immunotherapy response. Notably, our predictive model could further stratify low-risk and high-risk patients in terms of long-term survival.Comment: MICCAI 2020 (Early Accepted; Student Travel Award

Doping the holographic Mott insulator

Mott insulators form because of strong electron repulsions, being at the heart of strongly correlated electron physics. Conventionally these are understood as classical "traffic jams" of electrons described by a short-ranged entangled product ground state. Exploiting the holographic duality, which maps the physics of densely entangled matter onto gravitational black hole physics, we show how Mott-insulators can be constructed departing from entangled non-Fermi liquid metallic states, such as the strange metals found in cuprate superconductors. These "entangled Mott insulators" have traits in common with the "classical" Mott insulators, such as the formation of Mott gap in the optical conductivity, super-exchange-like interactions, and form "stripes" when doped. They also exhibit new properties: the ordering wave vectors are detached from the number of electrons in the unit cell, and the DC resistivity diverges algebraically instead of exponentially as function of temperature. These results may shed light on the mysterious ordering phenomena observed in underdoped cuprates.Comment: 27 pages, 9 figures. Accepted in Nature Physic

Electric-field control of spin waves at room temperature in multiferroic BiFeO3

To face the challenges lying beyond current CMOS-based technology, new paradigms for information processing are required. Magnonics proposes to use spin waves to carry and process information, in analogy with photonics that relies on light waves, with several advantageous features such as potential operation in the THz range and excellent coupling to spintronics. Several magnonic analog and digital logic devices have been proposed, and some demonstrated. Just as for spintronics, a key issue for magnonics is the large power required to control/write information (conventionally achieved through magnetic fields applied by strip lines, or by spin transfer from large spin-polarized currents). Here we show that in BiFeO3, a room-temperature magnetoelectric material, the spin wave frequency (>600 GHz) can be tuned electrically by over 30%, in a non-volatile way and with virtually no power dissipation. Theoretical calculations indicate that this effect originates from a linear magnetoelectric effect related to spin-orbit coupling induced by the applied electric field. We argue that these properties make BiFeO3 a promising medium for spin wave generation, conversion and control in future magnonics architectures.Comment: 3 figure

Thermal width and gluo-dissociation of quarkonium in pNRQCD

The thermal width of heavy-quarkonium bound states in a quark-gluon plasma has been recently derived in an effective field theory approach. Two phenomena contribute to the width: the Landau damping phenomenon and the break-up of a colour-singlet bound state into a colour-octet heavy quark-antiquark pair by absorption of a thermal gluon. In the paper, we investigate the relation between the singlet-to-octet thermal break-up and the so-called gluo-dissociation, a mechanism for quarkonium dissociation widely used in phenomenological approaches. The gluo-dissociation thermal width is obtained by convoluting the gluon thermal distribution with the cross section of a gluon and a 1S quarkonium state to a colour octet quark-antiquark state in vacuum, a cross section that at leading order, but neglecting colour-octet effects, was computed long ago by Bhanot and Peskin. We will, first, show that the effective field theory framework provides a natural derivation of the gluo-dissociation factorization formula at leading order, which is, indeed, the singlet-to-octet thermal break-up expression. Second, the singlet-to-octet thermal break-up expression will allow us to improve the Bhanot--Peskin cross section by including the contribution of the octet potential, which amounts to include final-state interactions between the heavy quark and antiquark. Finally, we will quantify the effects due to final-state interactions on the gluo-dissociation cross section and on the quarkonium thermal width.Comment: 17 pages, 6 figure

The Chemopreventive Effects of Protandim: Modulation of p53 Mitochondrial Translocation and Apoptosis during Skin Carcinogenesis

Protandim, a well defined dietary combination of 5 well-established medicinal plants, is known to induce endogenous antioxidant enzymes, such as manganese superoxide dismutase (MnSOD). Our previous studies have shown through the induction of various antioxidant enzymes, products of oxidative damage can be decreased. In addition, we have shown that tumor multiplicity and incidence can be decreased through the dietary administration of Protandim in the two-stage skin carcinogenesis mouse model. It has been demonstrated that cell proliferation is accommodated by cell death during DMBA/TPA treatment in the two-stage skin carcinogenesis model. Therefore, we investigated the effects of the Protandim diet on apoptosis; and proposed a novel mechanism of chemoprevention utilized by the Protandim dietary combination. Interestingly, Protandim suppressed DMBA/TPA induced cutaneous apoptosis. Recently, more attention has been focused on transcription-independent mechanisms of the tumor suppressor, p53, that mediate apoptosis. It is known that cytoplasmic p53 rapidly translocates to the mitochondria in response to pro-apoptotic stress. Our results showed that Protandim suppressed the mitochondrial translocation of p53 and mitochondrial outer membrane proteins such as Bax. We examined the levels of p53 and MnSOD expression/activity in murine skin JB6 promotion sensitive (P+) and promotion-resistant (P-) epidermal cells. Interestingly, p53 was induced only in P+ cells, not P- cells; whereas MnSOD is highly expressed in P- cells when compared to P+ cells. In addition, wild-type p53 was transfected into JB6 P- cells. We found that the introduction of wild-type p53 promoted transformation in JB6 P- cells. Our results suggest that suppression of p53 and induction of MnSOD may play an important role in the tumor suppressive activity of Protandim

Genome Expression Profile Analysis of the Immature Maize Embryo during Dedifferentiation

Maize is one of the most important cereal crops worldwide and one of the primary targets of genetic manipulation, which provides an excellent way to promote its production. However, the obvious difference of the dedifferentiation frequency of immature maize embryo among various genotypes indicates that its genetic transformation is dependence on genotype and immature embryo-derived undifferentiated cells. To identify important genes and metabolic pathways involved in forming of embryo-derived embryonic calli, in this study, DGE (differential gene expression) analysis was performed on stages I, II, and III of maize inbred line 18-599R and corresponding control during the process of immature embryo dedifferentiation. A total of ∼21 million cDNA tags were sequenced, and 4,849,453, 5,076,030, 4,931,339, and 5,130,573 clean tags were obtained in the libraries of the samples and the control, respectively. In comparison with the control, 251, 324 and 313 differentially expressed genes (DEGs) were identified in the three stages with more than five folds, respectively. Interestingly, it is revealed that all the DEGs are related to metabolism, cellular process, and signaling and information storage and processing functions. Particularly, the genes involved in amino acid and carbohydrate transport and metabolism, cell wall/membrane/envelope biogenesis and signal transduction mechanism have been significantly changed during the dedifferentiation. To our best knowledge, this study is the first genome-wide effort to investigate the transcriptional changes in dedifferentiation immature maize embryos and the identified DEGs can serve as a basis for further functional characterization