Harnessing Soluble NK Cell Killer Receptors for the Generation of Novel Cancer Immune Therapy

The natural cytotoxic receptors (NCRs) are a unique set of activating proteins expressed mainly on the surface of natural killer (NK) cells. The NCRs, which include three members; NKp46, NKp44 and NKp30, are critically involved in NK cytotoxicity against different targets, including a wide range of tumor cells derived from various origins. Even though the tumor ligands of the NCRs have not been identified yet, the selective manner by which these receptors target tumor cells may provide an excellent basis for the development of novel anti-tumor therapies. To test the potential use of the NCRs as anti-tumor agents, we generated soluble NCR-Ig fusion proteins in which the constant region of human IgG1 was fused to the extracellular portion of the receptor. We demonstrate, using two different human prostate cancer cell lines, that treatment with NKp30-Ig, dramatically inhibits tumor growth in vivo. Activated macrophages were shown to mediate an ADCC response against the NKp30-Ig coated prostate cell lines. Finally, the Ig fusion proteins were also demonstrated to discriminate between benign prostate hyperplasia and prostate cancer. This may provide a novel diagnostic modality in the difficult task of differentiating between these highly common pathological conditions

Reduction of species identification errors in surveys of marine wildlife abundance utilising unoccupied aerial vehicles (UAVs)

The advent of unoccupied aerial vehicles (UAVs) has enhanced our capacity to survey wildlife abundance, yet new protocols are still required for collecting, processing, and analysing image-type observations. This paper presents a methodological approach to produce informative priors on species misidentification probabilities based on independent experiments. We performed focal follows of known dolphin species and distributed our imagery amongst 13 trained observers. Then, we investigated the effects of reviewer-related variables and image attributes on the accuracy of species identification and level of certainty in observations. In addition, we assessed the number of reviewers required to produce reliable identification using an agreement-based framework compared with the majority rule approach. Among-reviewer variation was an important predictor of identification accuracy, regardless of previous experience. Image resolution and sea state exhibited the most pronounced effects on the proportion of correct identifications and the reviewers’ mean level of confidence. Agreement-based identification resulted in substantial data losses but retained a broader range of image resolutions and sea states than the majority rule approach and produced considerably higher accuracy. Our findings suggest a strong dependency on reviewer-related variables and image attributes, which, unless considered, may compromise identification accuracy and produce unreliable estimators of abundance

Detection and Molecular Characterization of 9000-Year-Old Mycobacterium tuberculosis from a Neolithic Settlement in the Eastern Mediterranean

Background: Mycobacterium tuberculosis is the principal etiologic agent of human tuberculosis. It has no environmental reservoir and is believed to have co-evolved with its host over millennia. This is supported by skeletal evidence of the disease in early humans, and inferred from M. tuberculosis genomic analysis. Direct examination of ancient human remains for M. tuberculosis biomarkers should aid our understanding of the nature of prehistoric tuberculosis and the host/pathogen relationship.Methodology/Principal Findings: We used conventional PCR to examine bone samples with typical tuberculosis lesions from a woman and infant, who were buried together in the now submerged site of Atlit-Yam in the Eastern Mediterranean, dating from 9250-8160 years ago. Rigorous precautions were taken to prevent contamination, and independent centers were used to confirm authenticity of findings. DNA from five M. tuberculosis genetic loci was detected and had characteristics consistent with extant genetic lineages. High performance liquid chromatography was used as an independent method of verification and it directly detected mycolic acid lipid biomarkers, specific for the M. tuberculosis complex.Conclusions/Significance: Human tuberculosis was confirmed by morphological and molecular methods in a population living in one of the first villages with evidence of agriculture and animal domestication. The widespread use of animals was not a source of infection but may have supported a denser human population that facilitated transmission of the tubercle bacillus. The similarity of the M. tuberculosis genetic signature with those of today gives support to the theory of a long-term co-existence of host and pathogen

Tuberculosis origin: The Neolithic scenario

This paper follows the dramatic changes in scientific research during the last 20 years regarding the relationship between the Mycobacterium tuberculosis complex and its hosts - bovids and/or humans. Once the M. tuberculosis and Mycobacterium bovis genomes were sequenced, it became obvious that the old story of M. bovis evolving into the human pathogen should be reversed, as M. tuberculosis is more ancestral than M. bovis. Nevertheless, the timescale and geographical origin remained an enigma. In the current study human and cattle bone samples were examined for evidence of tuberculosis from the site of Atlit-Yam in the Eastern Mediterranean, dating from 9250 to 8160 (calibrated) years ago. Strict precautions were used to prevent contamination in the DNA analysis, and independent centers used to confirm authenticity of findings. DNA from five M. tuberculosis genetic loci was detected and had characteristics consistent with extant genetic lineages. High performance liquid chromatography was used as an independent method of verification and it directly detected mycolic acid lipid biomarkers, specific for the M. tuberculosis complex. These, together with pathological changes detected in some of the bones, confirm the presence of the disease in the Levantine populations during the Pre-pottery Neolithic C period, more than 8000 years ago

Using resource graphs to represent conceptual change

We introduce resource graphs, a representation of linked ideas used when reasoning about specific contexts in physics. Our model is consistent with previous descriptions of resources and coordination classes. It can represent mesoscopic scales that are neither knowledge-in-pieces or large-scale concepts. We use resource graphs to describe several forms of conceptual change: incremental, cascade, wholesale, and dual construction. For each, we give evidence from the physics education research literature to show examples of each form of conceptual change. Where possible, we compare our representation to models used by other researchers. Building on our representation, we introduce a new form of conceptual change, differentiation, and suggest several experimental studies that would help understand the differences between reform-based curricula.Comment: 27 pages, 14 figures, no tables. Submitted for publication to the Physical Review Special Topics Physics Education Research on March 8, 200

Carbon stable isotope analysis of cereal remains as a way to reconstruct water availability: preliminary results

Reconstructing past water availability, both as rainfall and irrigation, is important to answer questions about the way society reacts to climate and its changes and the role of irrigation in the development of social complexity. Carbon stable isotope analysis of archaeobotanical remains is a potentially valuable method for reconstructing water availability. To further define the relationship between water availability and plant carbon isotope composition and to set up baseline values for the Southern Levant, grains of experimentally grown barley and sorghum were studied. The cereal crops were grown at three stations under five different irrigation regimes in Jordan. Results indicate that a positive but weak relationship exists between irrigation regime and total water input of barley grains, but no relationship was found for sorghum. The relationship for barley is site-specific and inter-annual variation was present at Deir ‘Alla, but not at Ramtha and Khirbet as-Samra

Is it harder to know or to reason? Analyzing two-tier science assessment items using the Rasch measurement model

Two-tier multiple-choice (TTMC) items are used to assess students’ knowledge of a scientific concept for tier 1 and their reasoning about this concept for tier 2. But are the knowledge and reasoning involved in these tiers really distinguishable? Are the tiers equally challenging for students? The answers to these questions influence how we use and interpret TTMC instruments. We apply the Rasch measurement model on TTMC items to see if the items are distinguishable according to different traits (represented by the tier), or according to different content sub-topics within the instrument, or to both content and tier. Two TTMC data sets are analyzed: data from Singapore and Korea on the Light Propagation Diagnostic Instrument (LPDI), data from the United States on the Classroom Test of Scientific Reasoning (CTSR). Findings for LPDI show that tier-2 reasoning items are more difficult than tier-1 knowledge items, across content sub-topics. Findings for CTSR do not show a consistent pattern by tier or by content sub-topic. We conclude that TTMC items cannot be assumed to have a consistent pattern of difficulty by tier—and that assessment developers and users need to consider how the tiers operate when administering TTMC items and interpreting results. Researchers must check the tiers’ difficulties empirically during validation and use. Though findings from data in Asian contexts were more consistent, further study is needed to rule out differences between the LPDI and CTSR instruments