Rice endosperm is cost-effective for the production of recombinant griffithsin with potent activity against HIV

Protein microbicides containing neutralizing antibodies and antiviral lectins may help to reduce the rate of infection with human immunodeficiency virus (HIV) if it is possible to manufacture the components in large quantities at a cost affordable in HIV‐endemic regions such as sub‐Saharan Africa. We expressed the antiviral lectin griffithsin (GRFT), which shows potent neutralizing activity against HIV, in the endosperm of transgenic rice plants (Oryza sativa), to determine whether rice can be used to produce inexpensive GRFT as a microbicide ingredient. The yield of (OS)GRFT in the best‐performing plants was 223 μg/g dry seed weight. We also established a one‐step purification protocol, achieving a recovery of 74% and a purity of 80%, which potentially could be developed into a larger‐scale process to facilitate inexpensive downstream processing. (OS)GRFT bound to HIV glycans with similar efficiency to GRFT produced in Escherichia coli. Whole‐cell assays using purified (OS)GRFT and infectivity assays using crude extracts of transgenic rice endosperm confirmed that both crude and pure (OS)GRFT showed potent activity against HIV and the crude extracts were not toxic towards human cell lines, suggesting they could be administered as a microbicide with only minimal processing. A freedom‐to‐operate analysis confirmed that GRFT produced in rice is suitable for commercial development, and an economic evaluation suggested that 1.8 kg/ha of pure GRFT could be produced from rice seeds. Our data therefore indicate that rice could be developed as an inexpensive production platform for GRFT as a microbicide component

Biochemical Properties of a Decoy Oligodeoxynucleotide Inhibitor of STAT3 Transcription Factor.

Cyclic STAT3 decoy (CS3D) is a second-generation, double-stranded oligodeoxynucleotide (ODN) that mimics a genomic response element for signal transducer and activator of transcription 3 (STAT3), an oncogenic transcription factor. CS3D competitively inhibits STAT3 binding to target gene promoters, resulting in decreased expression of proteins that promote cellular proliferation and survival. Previous studies have demonstrated antitumor activity of CS3D in preclinical models of solid tumors. However, prior to entering human clinical trials, the efficiency of generating the CS3D molecule and its stability in biological fluids should be determined. CS3D is synthesized as a single-stranded ODN and must have its free ends ligated to generate the final cyclic form. In this study, we report a ligation efficiency of nearly 95 percent. The ligated CS3D demonstrated a half-life of 7.9 h in human serum, indicating adequate stability for intravenous delivery. These results provide requisite biochemical characterization of CS3D that will inform upcoming clinical trials

Immunogenicity ofEscherichia coli O antigen in upper urinary tract infection

Immunogenicity ofEscherichia coli O antigen in upper urinary tract infection. The role of immunogenicity of the infecting organism (Escherichia coli) in the antibody response to O antigen in upper urinary tract infection was investigated Heat-killed vaccines were prepared from “immunogenic” organisms which had produced upper urinary tract infection associated with high titers of hemag-glutinating antibody to O antigen and “nonimmunogenic” organisms which had produced upper urinary tract infection without a rise in antibody titer. “Immunogenic” 06 vaccine produced high titers of antibody in patients regarded as possibly “poor producers” of antibody, but “nonimmunogenic” 011 vaccine was not associated with a rise in titer in patients previously regarded as “good producers”. These vaccines were significantly different in immunogenicity (P < 0.05). Five vaccines were tested in 50 rats. The difference in hemagglutinating titers to O antigen between 06 and 011 was highly significant (P < 0.001). Immunogenicity of the infecting organism appears to be a significant factor in determining antibody response to O antigen in upper urinary tract infection.Immunogénicité de l'antigène O d'Escherichia coli dans les infections du haut appareil urinaire. Le rôle de l'immunogénicité de l'organisme infectant (Escherichia coli) dans la réponse immune à l'antigène O au cours des infections du haut appareil urinaire a été étudié. Des vaccins tués par la chaleur ont été préparés à partir d'organismes “immunogéniques” qui ont été responsables d'infection du haut appareil urinaire associées à des titres élevés d'anticorps hémagglutinants contre l'antigène O et d'organismes “non immunogéniques” qui ont produit une infection du haut appareil sans augmentation du titre d'anticorps. Le vaccin “immunogénique” 06 produit des titres élevés d'anticorps chez des malades considérés comme de faibles producteurs d'anticorps et le vaccin “non immunogénique” 011 ne détermine pas d'augmentation du titre chez des malades antérieurement considérés comme de “bons producteurs”. Ces vaccins diffèrent significativement en “immunogénicité” (P < 0, 05). Cinq vaccins ont été essayés chez 50 rats. La différence dans les titres d'hémmaglutination vis à vis de l'antigène O est très significative entre 06 et 011 (P < 0, 001). L'immunogénicité de l'organisme infectant parait être un facteur important dans la détermination de la réponse immune à l'antigène O au cours des infections du haut appareil urinaire

Aristonectes quiriquinensis, sp. nov., a new highly derived elasmosaurid from the upper Maastrichtian of central Chile

This paper describes a new species of elasmosaurid plesiosaur, Aristonectes quiriquinensis, sp. nov., based on a partial skeleton recovered from upper Maastrichtian beds of the Quiriquina Formation of central Chile. The material described here consists of two skeletons, one collected near the village of Cocholgue, and a second juvenile specimen from Quiriquina Island. Prior to these finds, Aristonectes was viewed as a monospecific genus, including only the enigmatic Aristonectes parvidens, the holotype of which consists of an incomplete skull and incomplete postcranium. Other material referred to the genus includes an incomplete juvenile skull and other postcranial material from the upper Maastrichtian of Antarctica, as well as a partial skull from the Quiriquina Formation of central Chile. The relationships of Aristonectes have been controversial, with competing theories assigning the genus to Cryptoclididae, Elasmosauridae, and Aristonectidae; however, there is a developing consensus that Aristonectes is a derived elasmosaurid, and this paper gives strong evidence for this view. Comparison of the specimen here studied with the holotype of A. parvidens demonstrates that A. quiriquinensis is a distinct species. The completeness of the adult skeleton allows the first confident size estimates for adult Aristonectes. It is a large plesiosaurian with a relatively large skull with numerous homodont teeth, a moderately long and laterally compressed neck, and relatively narrow trunk, with slender and elongate forelimbs. The two specimens are restricted to the upper Maastrichtian of central Chile, posing questions concerning the austral circumpolar distribution of different elasmosaurids towards the end of the Cretaceous.Fil: Otero, Rodrigo A.. Universidad de Chile; ChileFil: Soto Acuña, Sergio. Museo Nacional de Historia Natural de Santiago; Chile. Universidad de Chile; ChileFil: O'Keefe, Frank Robin. Marshall University; Estados UnidosFil: O'gorman, Jose Patricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Paleontología Vertebrados; ArgentinaFil: Stinnesbeck, Wolfgang. Heidelberg University; AlemaniaFil: Suárez, Mario E.. Museo Nacional de Historia Natural de Santiago; Chile. Universidad de Chile; ChileFil: Rubilar-Rogers, David. Museo Nacional de Historia Natural de Santiago; Chile. Universidad de Chile; ChileFil: Salazar, Christian. Museo Nacional de Historia Natural de Santiago; Chile. Universidad de Chile; ChileFil: Quinzio Sinn, Luis Arturo. Universidad de Concepción; Chil

Intermediate statistics in quantum maps

We present a one-parameter family of quantum maps whose spectral statistics are of the same intermediate type as observed in polygonal quantum billiards. Our central result is the evaluation of the spectral two-point correlation form factor at small argument, which in turn yields the asymptotic level compressibility for macroscopic correlation lengths

DNA Methylation of the ABO Promoter Underlies Loss of ABO Allelic Expression in a Significant Proportion of Leukemic Patients

Background: Loss of A, B and H antigens from the red blood cells of patients with myeloid malignancies is a frequent occurrence. Previously, we have reported alterations in ABH antigens on the red blood cells of 55% of patients with myeloid malignancies. Methodology/Principal Findings: To determine the underlying molecular mechanisms of this loss, we assessed ABO allelic expression in 21 patients with ABH antigen loss previously identified by flow cytometric analysis as well as an additional 7 patients detected with ABH antigen changes by serology. When assessing ABO mRNA allelic expression, 6/12 (50%) patients with ABH antigen loss detected by flow cytometry and 5/7 (71%) of the patients with ABH antigen loss detected by serology had a corresponding ABO mRNA allelic loss of expression. We examined the ABO locus for copy number and DNA methylation alterations in 21 patients, 11 with loss of expression of one or both ABO alleles, and 10 patients with no detectable allelic loss of ABO mRNA expression. No loss of heterozygosity (LOH) at the ABO locus was observed in these patients. However in 8/11 (73%) patients with loss of ABO allelic expression, the ABO promoter was methylated compared with 2/10 (20%) of patients with no ABO allelic expression loss (P = 0.03). Conclusions/Significance: We have found that loss of ABH antigens in patients with hematological malignancies is associated with a corresponding loss of ABO allelic expression in a significant proportion of patients. Loss of ABO allelic expression was strongly associated with DNA methylation of the ABO promoter.Tina Bianco-Miotto, Damian J. Hussey, Tanya K. Day, Denise S. O'Keefe and Alexander Dobrovi

Estimating Distributed Representation Performance in Disaster-Related Social Media Classification

This paper examines the effectiveness of a range of pre-trained language representations in order to determine the informativeness and information type of social media in the event of natural or man-made disasters. Within the context of disaster tweet analysis, we aim to accurately analyse tweets while minimising both false positive and false negatives in the automated information analysis. The investigation is performed across a number of well known disaster-related twitter datasets. Models that are built from pre-trained word embeddings from Word2Vec, GloVe, ELMo and BERT are used for performance evaluation. Given the relative ubiquity of BERT as a standout language representation in recent times it was expected that BERT dominates results. However, results are more diverse, with classical Word2Vec and GloVe both displaying strong results. As part of the analysis, we discuss some challenges related to automated twitter analysis including the fine-tuning of language models to disaster-related scenarios

Acoustic Emission from crumpling paper

From magnetic systems to the crust of the earth, many physical systems that exibit a multiplicty of metastable states emit pulses with a broad power law distribution in energy. Digital audio recordings reveal that paper being crumpled, a system that can be easily held in hand, is such a system. Crumpling paper both using the traditional hand method and a novel cylindrical geometry uncovered a power law distribution of pulse energies spanning at least two decades: (exponent 1.3 - 1.6) Crumpling initally flat sheets into a compact ball (strong crumpling), we found little or no evidence that the energy distribution varied systematically over time or the size of the sheet. When we applied repetitive small deformations (weak crumpling) to sheets which had been previously folded along a regular grid, we found no systematic dependence on the grid spacing. Our results suggest that the pulse energy depends only weakly on the size of the paper regions responsible for sound production.Comment: 12 pages of text, 9 figures, submitted to Phys. Rev. E, additional information availible at http://www.msc.cornell.edu/~houle/crumpling

Navigating with grid and place cells in cluttered environments

Hippocampal formation contains several classes of neurons thought to be involved in navigational processes, in particular place cells and grid cells. Place cells have been associated with a topological strategy for navigation, while grid cells have been suggested to support metric vector navigation. Grid cell-based vector navigation can support novel shortcuts across unexplored territory by providing the direction toward the goal. However, this strategy is insufficient in natural environments cluttered with obstacles. Here, we show how navigation in complex environments can be supported by integrating a grid cell-based vector navigation mechanism with local obstacle avoidance mediated by border cells and place cells whose interconnections form an experience-dependent topological graph of the environment. When vector navigation and object avoidance fail (i.e., the agent gets stuck), place cell replay events set closer subgoals for vector navigation. We demonstrate that this combined navigation model can successfully traverse environments cluttered by obstacles and is particularly useful where the environment is underexplored. Finally, we show that the model enables the simulated agent to successfully navigate experimental maze environments from the animal literature on cognitive mapping. The proposed model is sufficiently flexible to support navigation in different environments, and may inform the design of experiments to relate different navigational abilities to place, grid, and border cell firing