Modeling lifetime greenhouse gas emissions associated with materials for various end-of-life treatments.

This research has developed mathematical models for computing lifetime greenhouse gas (GHG) emissions associated with materials. The models include embodied carbon (EC) emissions from the manufacture of materials, and GHG emissions from incineration, or landfill gas (LFG) production from landfill disposal of the material beyond their service lives. The models are applicable to all materials; however, their applications here are demonstrated for the lumber from a residential building with 50- and 100-year service lives, and with incineration, landfill, and deconstruction as end-of-life treatments. This paper introduces a new metric for lifetime GHG emissions associated with materials termed "Global Warming Impact of Materials (GWIM)." The GWIM is subdivided into two portions: (i) productive portion (GWIMp) that includes the materials' emissions until the service life of the facility and (ii) non-productive portion (GWIMnp) which includes the materials' GHG emissions beyond the service life until they are eliminated from the atmosphere. In place of the current, static, EC measurements (kgCO2e or MTCO2e), this model reports the GWIMs in units of kgCO2e-years or MTCO2e-years, which includes the effects of "time of use" of a facility. Using the models, this paper has computed GHG reductions by deconstruction, with material recoveries of 30%, 50%, and 70% at demolition for reuse, recycle, or repurpose. A 70% material recovery, after a 50-year service life of the building, affected a savings of 47% and 52% if the remaining 30% debris was incinerated or landfilled respectively. All of the values computed using models checked out with manual calculations.

Penicillin-binding protein 7/8 contributes to the survival of Acinetobacter baumannii in vitro and in vivo.

BACKGROUND: Acinetobacter baumannii is a bacterial pathogen of increasing medical importance. Little is known about genes important for its survival in vivo. METHODS AND RESULTS: Screening of random transposon mutants of the model pathogen AB307-0294 identified the mutant AB307.27. AB307.27 contained its transposon insertion in pbpG, which encodes the putative low-molecular-mass penicillin-binding protein 7/8 (PBP-7/8). AB307.27 was significantly killed in ascites (P<.001), but its growth in Luria-Bertani broth was similar to that of its parent, AB307-0294 (P=.13). The survival of AB307.27 was significantly decreased in a rat soft-tissue infection model (P<.001) and a rat pneumonia model (P=.002), compared with AB307-0294. AB307.27 was significantly killed in 90% human serum in vitro, compared with AB307-0294 (P<.001). Electron microscopy demonstrated more coccobacillary forms of AB307.27, compared with AB307-0294, suggesting a possible modulation in the peptidoglycan, which may affect susceptibility to host defense factors. CONCLUSIONS: These findings demonstrate that PBP-7/8 contributes to the pathogenesis of A. baumannii. PBP-7/8 either directly or indirectly contributes to the resistance of AB307-0294 to complement-mediated bactericidal activity. An understanding of how PBP-7/8 contributes to serum resistance will lend insight into the role of this low-molecular-mass PBP whose function is poorly understood.

Comparative genome sequence analysis of multidrug-resistant Acinetobacter baumannii.

The recent emergence of multidrug resistance (MDR) in Acinetobacter baumannii has raised concern in health care settings worldwide. In order to understand the repertoire of resistance determinants and their organization and origins, we compared the genome sequences of three MDR and three drug-susceptible A. baumannii isolates. The entire MDR phenotype can be explained by the acquisition of discrete resistance determinants distributed throughout the genome. A comparison of closely related MDR and drug-susceptible isolates suggests that drug efflux may be a less significant contributor to resistance to certain classes of antibiotics than inactivation enzymes are. A resistance island with a variable composition of resistance determinants interspersed with transposons, integrons, and other mobile genetic elements is a significant but not universal contributor to the MDR phenotype. Four hundred seventy-five genes are shared among all six clinical isolates but absent from the related environmental species Acinetobacter baylyi ADP1. These genes are enriched for transcription factors and transporters and suggest physiological features of A. baumannii that are related to adaptation for growth in association with humans.

Heat shock proteins HSP70 and GP96: structural insights.

Several heat shock proteins (HSPs) act as potent adjuvants for eliciting anti-tumor immunity. HSP-based tumor vaccine strategies have been highly successful in animal models and are undergoing testing in clinical trials. It is generally accepted that HSPs, functioning as chaperones for tumor antigens, elicit tumor-specific adaptive immune responses. HSPs also appear to induce innate immune responses in an antigen-independent fashion. Innate responses generated by HSPs may contribute to anti-tumor immunity. Immunologically active chaperones with anti-tumor activity are referred to as "immunochaperones". Here, we review the studies that address the role of structural domains or regions of the immunochaperones HSP70 and GP96 that may be involved in the induction of adaptive or innate immune responses.

Heat shock proteins and scavenger receptors: role in adaptive immune responses.

Tumor-derived heat shock proteins have shown promise as anti-cancer vaccines in clinical trials. Heat shock proteins (HSPs) can generate potent anti-tumor immunity and elicit antigen-specific CD8+ T cell responses in murine studies. Antigen presenting cells (APC), such as macrophages and dendritic cells (DCs), can elicit antigen-specific CD8+ T cell responses mediated by HSPs. CD91 was the first identified endocytic scavenger receptor for HSPs on APC that can facilitate the process of cross-presentation. Other scavenger receptors may also play a similar role in this process. The present review critically evaluates the identified HSP endocytic receptors on APCs that may generate adaptive immune responses. A better understanding of this interaction between HSPs and APCs may further unravel mechanisms of immunoadjuvant function of HSPs.

Cancer immunotherapy and heat-shock proteins: promises and challenges.

Recent mechanistic studies on the role of heat-shock proteins (HSPs) to induce innate and adaptive immune responses have resulted in conflicting reports. Whereas some groups reported that HSPs have direct immunological function, others emphasised the endotoxin contamination of HSP preparations and questioned the antigen-specificity of HSP vaccines. The present review will discuss these issues and suggest that HSPs have diverse and distinct immunological functions that could be superimposed on effects resulting from endotoxin contamination or misunderstood by using experimental procedures with inadequate controls. To understand the actual function of HSPs in their interaction with the immune system, methods and procedures need to be optimised and appropriate controls need to be used. These points should also clarify the conflicting findings about HSPs and promote our knowledge about other immuologically important components that may be present in HSP preparations.

The chaperoning properties of mouse grp170, a member of the third family of hsp70 related proteins.

The 170 kDa glucose-regulated protein (grp170) is an endoplasmic reticulum resident protein that shares some sequence homology with both the hsp70 and hsp110 heat shock protein (hsp) families, yet is representative of a third and unique family of stress proteins. Despite observations indicating important roles in normal cellular functions, the in vitro chaperone properties of grp170 have not been rigorously examined. We have cloned mouse grp170 and expressed the recombinant protein in a baculovirus expression system. The function of recombinant grp170 was then assessed by determining its ability to bind to and prevent aggregation of heat-denatured luciferase. Grp170 maintains heat-denatured luciferase in a soluble state in the absence of ATP. In the presence of rabbit reticulocyte lysate, grp170 can refold and partially restore function to denatured luciferase. The chaperoning function of grp170 was also studied using domain deletion mutants, designed using the crystal structure of DnaK and the theoretical secondary structure of hsp110 as guides. Unlike hsp70 and hsp110, grp170 appears to have two domains capable of binding denatured luciferase and inhibiting its heat-induced aggregation. The two domains were identified as being similar to the classical beta-sandwich peptide binding domain and the C-terminal alpha-helical domain in hsp70 and hsp110. The ability of the C-terminal region to bind peptides is a unique feature of grp170.