Investigation of the human antibody response to influenza virus infection has been largely limited to serology, with relatively little analysis at the molecular level. The 1918 H1N1 influenza virus pandemic was the most severe of the modern era 1 . Recent work has recovered the gene sequences of this unusual strain 2 , so that the 1918 pandemic virus could be reconstituted to display its unique virulence phenotypes 3,4 . However, little is known about adaptive immunity to this virus. We took advantage of the 1918 virus sequencing and the resultant production of recombinant 1918 hemagglutinin (HA) protein antigen to characterize at the clonal level neutralizing antibodies induced by natural exposure of survivors to the 1918 pandemic virus. In our study, each of 32 individuals tested that were born in or before 1915 exhibited seroreactivity with 1918 virus, nearly 90 years after the pandemic. Seven of 8 donor samples tested had circulating B cells that secreted antibodies that bound 1918 HA. We isolated B cells from subjects and generated five monoclonal antibodies that exhibited potent neutralizing activity against 1918 virus from three separate donors. These antibodies also cross-reacted with the genetically similar HA of a 1930 swine H1N1 influenza strain, but not with HAs of more contemporary human influenza viruses. The antibody genes exhibited an unusually Correspondence should be addressed to JEC (James.Crowe@vanderbilt.edu), CFB (Chris.Basler@mssm.edu) or ELA (Eric.Altschuler@umdnj.edu). Supplementary Information is linked to the online version of the paper at www.nature.com/nature.Author Contributions XY and TT contributed equally to this work. XY, PAM, MDH and FSH made and cloned the mAbs, sequenced antibody genes, and performed IF experiments, CJK performed biosensor studies, TMT, CP, and LAP designed and performed in vivo studies, OM sequenced the HA genes of the H1N1 viruses used in this study and performed ELISA assays with these viruses. PVA assisted with HAI and neutralization assays and with cloning of recombinant HA molecules. JS and IAW provided recombinant HA; ELA led the clinical recruitment, ELA, CFB and JEC conceived of the experimental plan. CFB and JEC wrote the manuscript. All authors discussed the results and commented on the manuscript.Antibody nucleotide sequences are deposited in GenBank, accession numbers EU169674 through EU169679 and EU825947 through EU825950.Reprints and permissions information is available at npg.nature.com/reprints and permissions.The authors declare no competing financial interests. NIH Public Access Author ManuscriptNature. Author manuscript; available in PMC 2010 April 3. . We collected transformed cells from the wells corresponding to supernates exhibiting the highest levels of specific binding to the 1918 HA (derived from five donors) and fused them to the HMMA2.5 nonsecreting myeloma partner 7 using an electrofusion technique 8 . We isolated 17 unique hybridoma cell lines that secreted antibodies reactive with the 1918 HA from cell lines derived fro...

[reaction: see text] A new fluorescent probe, salicylaldehyde rhodamine B hydrazone (1), was synthesized and displayed selective Cu(II)-amplified absorbance and fluorescence emission above 500 nm in neutral buffered media. Upon the addition of Cu(II), the spirolactam ring of 1 was opened and a 1:1 metal-ligand complex was formed. The detection of Cu(II) by 1 at a lower micromolar level was successful even in buffered water.

Despite recent advances in face recognition using deep learning, severe accuracy drops are observed for large pose variations in unconstrained environments. Learning poseinvariant features is one solution, but needs expensively labeled large-scale data and carefully designed feature learning algorithms. In this work, we focus on frontalizing faces in the wild under various head poses, including extreme profile views. We propose a novel deep 3D Morphable Model (3DMM) conditioned Face Frontalization Generative Adversarial Network (GAN), termed as FF-GAN, to generate neutral head pose face images. Our framework differs from both traditional GANs and 3DMM based modeling. Incorporating 3DMM into the GAN structure provides shape and appearance priors for fast convergence with less training data, while also supporting end-to-end training. The 3DMMconditioned GAN employs not only the discriminator and generator loss but also a new masked symmetry loss to retain visual quality under occlusions, besides an identity loss to recover high frequency information. Experiments on face recognition, landmark localization and 3D reconstruction consistently show the advantage of our frontalization method on faces in the wild datasets. 1 * This work was supported by a research gift from NEC Labs to Michigan State University.1 Detail results and resources can be refered to: http://cvlab.cse. msu.edu/project-face-frontalization.html. 3DMM Coefficients Pose-Variant Input Recogni8on Engine Frontalized Output Generator FF-GAN D Discriminator Extreme Pose Input Frontalized Output

This study demonstrates that syndecan functions as an in trans HIV receptor. We show that syndecan, when expressed in nonpermissive cells, becomes the major mediator for HIV adsorption. This adsorption is mediated by the binding of gp120 to the heparan sulfate chains of syndecan. Although syndecan does not substitute for HIV entry receptors, it enhances the in trans infectivity of a broad range of primate lentiviruses including primary viruses produced from PBMCs. Furthermore, syndecan preserves virus infectivity for a week, whereas unbound virus loses its infectivity in less than a day. Moreover, we obtain evidence suggesting that the vast syndecan-rich endothelial lining of the vasculature can provide a microenvironment which boosts HIV replication in T cells.

Abstract

Despite the large volume of face recognition datasets, there is a significant portion of subjects, of which the samples are insufficient and thus under-represented. Ignoring such significant portion results in insufficient training data. Training with under-represented data leads to biased classifiers in conventionally-trained deep networks. In this paper, we propose a center-based feature transfer framework to augment the feature space of under-represented subjects from the regular subjects that have sufficiently diverse samples. A Gaussian prior of the variance is assumed across all subjects and the variance from regular ones are transferred to the under-represented ones. This encourages the under-represented distribution to be closer to the regular distribution. Further, an alternating training regimen is proposed to simultaneously achieve less biased classifiers and a more discriminative feature representation. We conduct ablative study to mimic the under-represented datasets by varying the portion of under-represented classes on the MS-Celeb-1M dataset. Advantageous results on LFW, IJB-A and MS-Celeb-1M demonstrate the effectiveness of our feature transfer and training strategy, compared to both general baselines and state-of-the-art methods. Moreover, our feature transfer successfully presents smooth visual interpolation, which conducts disentanglement to preserve identity of a class while augmenting its feature space with non-identity variations such as pose and lighting.

We sought to develop and optimize a hybridoma-based technology for generating human hybridomas that secrete virus-specific monoclonal antibodies for clinical diagnosis and therapy. We developed a novel electrofusion protocol for efficiently fusing Epstein-Barr virus (EBV)-transformed human B cells with myeloma partners. We tested seven myeloma cell lines and achieved highest efficiency when the HMMA 2.5 line was used. We optimized the electrofusion process by improving cell treatments before and after electrofusion as well as varying cell ratios, fusion medium and other experimental parameters. Our fusion efficiency increased remarkably to 0.43%, a significant improvement over the efficiency of previous PEG-based or other electrofusion methods. Using the optimized protocol, we obtained human hybridomas that secrete fully human monoclonal antibodies against two major human respiratory pathogens: respiratory syncytial virus (RSV) and an influenza H3N2 vaccine virus strain. In conclusion, we have developed an efficient and routine approach for the generation of human hybridomas secreting functional human virus-specific monoclonal antibodies.

Photochromic molecules are widely applied in chemistry, physics, biology, and materials science. Although a few photochromic systems have been developed before, their applications are still limited by complicated synthesis, low fatigue resistance, or incomplete light conversion. Rhodamine is a class of dyes with excellent optical properties including long-wavelength absorption, large absorption coefficient, and high photostability in its ring-open form. It is an ideal chromophore for the development of new photochromic systems. However, known photochromic rhodamine derivatives, such as amides, exhibit only millisecond lifetimes in their colored ring-open forms, making their application very limited and difficult. In this work, rhodamine B salicylaldehyde hydrazone metal complex was found to undergo intramolecular ring-open reactions upon UV irradiation, which led to a distinct color and fluorescence change both in solution and in solid matrix. The complex showed good fatigue resistance for the reversible photochromism and long lifetime for the ring-open state. Interestingly, the thermal bleaching rate was tunable by using different metal ions, temperatures, solvents, and chemical substitutions. It was proposed that UV light promoted isomerization of the rhodamine B derivative from enol-form to keto-form, which induced ring-opening of the rhodamine spirolactam in the complex to generate color. The photochromic system was successfully applied for photoprinting and UV strength measurement in the solid state. As compared to other reported photochromic molecules, the system in this study has its advantages of facile synthesis and tunable thermal bleaching rate, and also provides new insights into the development of photochromic materials based on metal complex and spirolactam-containing dyes.