The Nontriviality of Trivial General Covariance: How Electrons Restrict 'Time' Coordinates, Spinors (Almost) Fit into Tensor Calculus, and 7/16 of a Tetrad Is Surplus Structure

It is a commonplace that any theory can be written in any coordinates via tensor calculus. But it is claimed that spinors as such cannot be represented in coordinates in a curved space-time. What general covariance means for theories with fermions is thus unclear. In fact both commonplaces are wrong. Though it is not widely known, Ogievetsky and Polubarinov (OP) constructed spinors in coordinates in 1965, helping to spawn nonlinear group representations. Locally, these spinors resemble the orthonormal basis or "tetrad" formalism in the symmetric gauge, but they are conceptually self-sufficient. The tetrad formalism is de-Ockhamized, with 6 extra fields and 6 compensating gauge symmetries. OP spinors, as developed nonperturbatively by Bilyalov, admit any coordinates at a point, but "time" must be listed first: the product of the metric components and the matrix diag(-1,1,1,1) must have no negative eigenvalues to yield a real symmetric square root function of the metric. Thus the admissible coordinates depend on the types and values of the fields. Apart from coordinate order and spinorial two-valuedness, OP spinors form, with the metric, a nonlinear geometric object, with Lie and covariant derivatives. Such spinors avoid a spurious absolute object in the Anderson-Friedman analysis of substantive general covariance. They also permit the gauge-invariant localization of the infinite-component gravitational energy in GR. Density-weighted spinors exploit the conformal invariance of the massless Dirac equation to show that the volume element is absent. Thus instead of a matrix with 16 components, one can use weighted OP spinors coupled to the 9-component symmetric unimodular square root of the conformal metric density. The surprising mildness of the restrictions on coordinates for the Schwarzschild solution is exhibited. (edited)Comment: Forthcoming in \textit{Studies in History and Philosophy of Modern Physics

A review of zoonotic infection risks associated with the wild meat trade in Malaysia.

The overhunting of wildlife for food and commercial gain presents a major threat to biodiversity in tropical forests and poses health risks to humans from contact with wild animals. Using a recent survey of wildlife offered at wild meat markets in Malaysia as a basis, we review the literature to determine the potential zoonotic infection risks from hunting, butchering and consuming the species offered. We also determine which taxa potentially host the highest number of pathogens and discuss the significant disease risks from traded wildlife, considering how cultural practices influence zoonotic transmission. We identify 51 zoonotic pathogens (16 viruses, 19 bacteria and 16 parasites) potentially hosted by wildlife and describe the human health risks. The Suidae and the Cervidae families potentially host the highest number of pathogens. We conclude that there are substantial gaps in our knowledge of zoonotic pathogens and recommend performing microbial food safety risk assessments to assess the hazards of wild meat consumption. Overall, there may be considerable zoonotic risks to people involved in the hunting, butchering or consumption of wild meat in Southeast Asia, and these should be considered in public health strategies

Minimum Information about T Regulatory Cells: A Step toward Reproducibility and Standardization.

Cellular therapies with CD4+ T regulatory cells (Tregs) hold promise of efficacious treatment for the variety of autoimmune and allergic diseases as well as posttransplant complications. Nevertheless, current manufacturing of Tregs as a cellular medicinal product varies between different laboratories, which in turn hampers precise comparisons of the results between the studies performed. While the number of clinical trials testing Tregs is already substantial, it seems to be crucial to provide some standardized characteristics of Treg products in order to minimize the problem. We have previously developed reporting guidelines called minimum information about tolerogenic antigen-presenting cells, which allows the comparison between different preparations of tolerance-inducing antigen-presenting cells. Having this experience, here we describe another minimum information about Tregs (MITREG). It is important to note that MITREG does not dictate how investigators should generate or characterize Tregs, but it does require investigators to report their Treg data in a consistent and transparent manner. We hope this will, therefore, be a useful tool facilitating standardized reporting on the manufacturing of Tregs, either for research purposes or for clinical application. This way MITREG might also be an important step toward more standardized and reproducible testing of the Tregs preparations in clinical applications

Heme oxygenase-1 protects tumor cells against photodynamic therapy-mediated cytotoxicity

Photodynamic therapy is a promising antitumor treatment modality approved for the management of both early and advanced tumors. The mechanisms of its antitumor action include generation of singlet oxygen and reactive oxygen species that directly damage tumor cells and tumor vasculature. A number of mechanisms seem to be involved in the protective responses to PDT that include activation of transcription factors, heat shock proteins, antioxidant enzymes and antiapoptotic pathways. Elucidation of these mechanisms might result in the design of more effective combination strategies to improve the antitumor efficacy of PDT. Using DNA microarray analysis to identify stress-related genes induced by Photofrin-mediated PDT in colon adenocarcinoma C-26 cells, we observed a marked induction of heme oxygenase-1 (HO-1). Induction of HO-1 with hemin or stable transfection of C-26 with a plasmid vector encoding HO-1 increased resistance of tumor cells to PDT-mediated cytotoxicity. On the other hand, zinc (II) propoporphyrin IX, an HO-1 inhibitor, markedly augmented PDT-mediated cytotoxicity towards C-26 and human ovarian carcinoma MDAH2774 cells. Neither bilirubin, biliverdin nor carbon monoxide, direct products of HO-1 catalysed heme degradation, was responsible for cytoprotection. Importantly, desferrioxamine, a potent iron chelator significantly potentiated cytotoxic effects of PDT. Altogether our results indicate that HO-1 is involved in an important protective mechanism against PDT-mediated phototoxicity and administration of HO-1 inhibitors might be an effective way to potentiate antitumor effectiveness of PDT