Addressing the Role of Electrode Microstructure in Li-Ion Battery Thermo-Electrochemical Interaction

Lithium-ion batteries are a ubiquitous part of modern technology as portability and reusability are heavily emphasized. As this is the case, it is important to further improve their electrochemical capabilities while minimizing the increase in thermal effects and maximizing safety. There are many ways to do this, but one area that has had little focus is the role of microstructure morphology on the thermo-electrochemical performance of the cell. Thus, a study was done to characterize how changes in the microstructure affect properties pertinent to the thermal and electrochemical characterization. The thermal and electrochemical effects were then characterized considering the changes in the microstructure. The research done here has developed functional relationships that can be used to determine the active area, conductivity, and tortuosity in a graphite anode and NMC cathode. Changes in the porosity volume percentage, binder morphology, and binder volume percentage can cause significant variation in these properties. As those properties change, there are possibly significant changes in the overpotential, and concentration and potential gradient that then change the temperature rise and electrochemical performance in the cell

Addressing the Role of Electrode Microstructure in Li-Ion Battery Thermo-Electrochemical Interaction

Lithium-ion batteries are a ubiquitous part of modern technology as portability and reusability are heavily emphasized. As this is the case, it is important to further improve their electrochemical capabilities while minimizing the increase in thermal effects and maximizing safety. There are many ways to do this, but one area that has had little focus is the role of microstructure morphology on the thermo-electrochemical performance of the cell. Thus, a study was done to characterize how changes in the microstructure affect properties pertinent to the thermal and electrochemical characterization. The thermal and electrochemical effects were then characterized considering the changes in the microstructure. The research done here has developed functional relationships that can be used to determine the active area, conductivity, and tortuosity in a graphite anode and NMC cathode. Changes in the porosity volume percentage, binder morphology, and binder volume percentage can cause significant variation in these properties. As those properties change, there are possibly significant changes in the overpotential, and concentration and potential gradient that then change the temperature rise and electrochemical performance in the cell

NF-κB RelB Forms an Intertwined Homodimer

SummaryThe X-ray structure of the RelB dimerization domain (DD) reveals that the RelBDD assumes an unexpected intertwined fold topology atypical of other NF-κB dimers. All typical NF-κB dimers are formed by the association of two independently folded immunoglobulin (Ig) domains. In RelBDD, two polypeptides reconstruct both Ig domains in the dimer with an extra β sheet connecting the two domains. Residues most critical to NF-κB dimer formation are invariant in RelB, and Y300 plays a positive role in RelBDD dimer formation. The presence of RelB-specific nonpolar residues at the surface removes several intradomain surface hydrogen bonds that may render the domain fold unstable. Intertwining may stabilize the RelBDD homodimer by forming the extra β sheet. We show that, as in the crystal, RelB forms an intertwined homodimer in solution. We suggest that the transiently stable RelB homodimer might prevent its rapid degradation, allowing for heterodimer formation with p50 and p52

A structural basis for IκB kinase 2 activation via oligomerization-dependent trans auto-phosphorylation.

Activation of the IκB kinase (IKK) is central to NF-κB signaling. However, the precise activation mechanism by which catalytic IKK subunits gain the ability to induce NF-κB transcriptional activity is not well understood. Here we report a 4 Å x-ray crystal structure of human IKK2 (hIKK2) in its catalytically active conformation. The hIKK2 domain architecture closely resembles that of Xenopus IKK2 (xIKK2). However, whereas inactivated xIKK2 displays a closed dimeric structure, hIKK2 dimers adopt open conformations that permit higher order oligomerization within the crystal. Reversible oligomerization of hIKK2 dimers is observed in solution. Mutagenesis confirms that two of the surfaces that mediate oligomerization within the crystal are also critical for the process of hIKK2 activation in cells. We propose that IKK2 dimers transiently associate with one another through these interaction surfaces to promote trans auto-phosphorylation as part of their mechanism of activation. This structure-based model supports recently published structural data that implicate strand exchange as part of a mechanism for IKK2 activation via trans auto-phosphorylation. Moreover, oligomerization through the interfaces identified in this study and subsequent trans auto-phosphorylation account for the rapid amplification of IKK2 phosphorylation observed even in the absence of any upstream kinase

Interactions of APE1 with a redox inhibitor: Evidence for an alternate conformation of the enzyme

Apurinic/apyrimidinic endonuclease (APE1) is an essential base excision repair protein that also functions as a reduction and oxidation (redox) factor in mammals. Through a thiol-based mechanism, APE1 reduces a number of important transcription factors, including AP-1, p53, NF-κB, and HIF-1α. What is known about the mechanism to date is that the buried residues Cys 65 and Cys 93 are critical for APE1’s redox activity. To further detail the redox mechanism, we developed a chemical footprinting−mass spectrometric assay using N-ethylmaleimide (NEM), an irreversible Cys modifier, to characterize the interaction of the redox inhibitor, E3330, with APE1. When APE1 was incubated with E3330, two NEM-modified products were observed, one with two and a second with seven added NEMs; this latter product corresponds to a fully modified APE1. In a similar control reaction without E3330, only the +2NEM product was observed in which the two solvent-accessible Cys residues, C99 and C138, were modified by NEM. Through hydrogen−deuterium amide exchange with analysis by mass spectrometry, we found that the +7NEM-modified species incorporates approximately 40 more deuterium atoms than the native protein, which exchanges nearly identically as the +2NEM product, suggesting that APE1 can be trapped in a partially unfolded state. E3330 was also found to increase the extent of disulfide bond formation involving redox critical Cys residues in APE1 as assessed by liquid chromatography and tandem mass spectrometry, suggesting a basis for its inhibitory effects on APE1’s redox activity. Collectively, our results suggest that APE1 adopts a partially unfolded state, which we propose is the redox active form of the enzyme

Fatty acid profiles of muscle, liver, heart and kidney of Australian prime lambs fed different polyunsaturated fatty acids enriched pellets in a feedlot system

We investigated the effect of various dietary polyunsaturated fatty acid (PUFA) sources on the fatty acid profiles of muscle, liver, heart and kidney of Australian prime lambs. Seventy-two White Suffolk x Corriedale first-cross lambs weaned at 6 months of age were randomly allocated to the following six treatments: (1) Control: Lucerne hay only; wheat-based pellets infused with 50 ml/kg dry matter (DM) of oil from (2) rice bran (RBO); (3) canola (CO); (4) rumen-protected (RPO), (5) flaxseed (FSO) and (6) safflower (SO) sources in a completely randomized experimental design. Lambs in CO, FSO, SO and RPO treatments achieved contents of eicosapentaenoic acid (EPA, 22:5n-3) plus docosahexaenoic acid (DHA, 22:6n-3) in the longissimus dorsi muscle ranging from 31.1 to 57.1 mg/135 g, over and above the 30 mg per standard serve (135 g) threshold for “source” claim under the Australian guidelines. There was no difference in n-3 LC-PUFA contents in longissimus dorsi muscle of lambs fed dietary oils of plant origin. The highest 18:3n-3 (ALA) contents achieved with FSO diet in the muscle, liver and heart were 45.6, 128.1 and 51.3 mg/100 g, respectively. Liver and kidney contained high contents of n-3 LC-PUFA (ranging from 306.7 to 598.2 mg/100 g and 134.0 to 300.4 mg/100 g, respectively), with all values readily exceeding the ‘good source’ status (60 mg per serve under Australian guidelines). The liver and kidney of PUFA fed lambs can be labelled as ‘good source’ of n-3 LC-PUFA based on EPA and DHA contents stipulated by the Food Standards of Australia and New Zealand guidelines. Therefore, if lamb consumers consider eating the liver and kidney as their dietary protein sources, they can adequately obtain the associated health benefits of n-3 LC-PUFA

Clinical Implications of Combinatorial Pharmacogenomic Tests Based on Cytochrome P450 Variant Selection

Despite the potential to improve patient outcomes, the application of pharmacogenomics (PGx) is yet to be routine. A growing number of PGx implementers are leaning toward using combinatorial PGx (CPGx) tests (i.e., multigene tests) that are reusable over patients’ lifetimes. However, selecting a single best available CPGx test is challenging owing to many patient- and population-specific factors, including variant frequency differences across ethnic groups. The primary objective of this study was to evaluate the detection rate of currently available CPGx tests based on the cytochrome P450 (CYP) gene variants they target. The detection rate was defined as the percentage of a given population with an “altered metabolizer” genotype predicted phenotype, where a CPGx test targeted both gene variants a prospective diplotypes. A potential genotype predicted phenotype was considered an altered metabolizer when it resulted in medication therapy modification based on Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. Targeted variant CPGx tests found in the Genetic Testing Registry (GTR), gene selection information, and diplotype frequency data from the Pharmacogenomics Knowledge Base (PharmGKB) were used to determine the detection rate of each CPGx test. Our results indicated that the detection rate of CPGx tests covering CYP2C19, CYP2C9, CYP2D6, and CYP2B6 show significant variation across ethnic groups. Specifically, the Sub-Saharan Africans have 63.9% and 77.9% average detection rates for CYP2B6 and CYP2C19 assays analyzed, respectively. In addition, East Asians (EAs) have an average detection rate of 55.1% for CYP2C9 assays. Therefore, the patient’s ethnic background should be carefully considered in selecting CPGx tests

Practical and Pedagogical Issues for Teacher Adoption of IMS Learning Design Standards in Moodle LMS

Commentary on: Learning Design: A handbook on modelling and delivering networked education and training. (Koper and Tattersall, 2005) Abstract: Integrating the specifications and tools for IMS-Learning Design (IMS, 2003) into Moodle (Moodle, 2003), an open-source Learning Management System (LMS), is not just a technological question, but also relates to practical, pedagogical, and philosophical issues. This study documents the discussions and experiments of a team of teachers active in the Moodle community who are concerned with the development of international standards in future versions of Moodle. In the course (Moodle, 2005a) of studying the book, Learning Design (Koper and Tattersall, 2005), participants analysed the implications of integrating the LD specification into Moodle and the operation of various LD tools (CopperCore, Reload) and related tools (LAMS) within the Moodle environment. These differences were then summarized into general implications for future versions of both Moodle and Learning Design. This study concludes that continued, open dialogue between teachers and developers of both LD and Moodle is necessary to achieve transparent integration. Authors belong to the Moodle Community Learning Design Book Study Group. Editors: Colin Tattersall and Rob Koper

Immunization with Cocktail of HIV-Derived Peptides in Montanide ISA-51 Is Immunogenic, but Causes Sterile Abscesses and Unacceptable Reactogenicity

BACKGROUND: A peptide vaccine was produced containing B and T cell epitopes from the V3 and C4 Envelope domains of 4 subtype B HIV-1 isolates (MN, RF, CanO, & Ev91). The peptide mixture was formulated as an emulsion in incomplete Freund's adjuvant (IFA). METHODS: Low-risk, healthy adult subjects were enrolled in a randomized, placebo-controlled dose-escalation study, and selected using criteria specifying that 50% in each study group would be HLA-B7+. Immunizations were scheduled at 0, 1, and 6 months using a total peptide dose of 1 or 4 mg. Adaptive immune responses in16 vaccine recipients and two placebo recipients after the 2nd immunization were evaluated using neutralization assays of sera, as well as ELISpot and ICS assays of cryopreserved PBMCs to assess CD4 and CD8 T-cell responses. In addition, (51)Cr release assays were performed on fresh PBMCs following 14-day stimulation with individual vaccine peptide antigens. RESULTS: 24 subjects were enrolled; 18 completed 2 injections. The study was prematurely terminated because 4 vaccinees developed prolonged pain and sterile abscess formation at the injection site-2 after dose 1, and 2 after dose 2. Two other subjects experienced severe systemic reactions consisting of headache, chills, nausea, and myalgia. Both reactions occurred after the second 4 mg dose. The immunogenicity assessments showed that 6/8 vaccinees at each dose level had detectable MN-specific neutralizing (NT) activity, and 2/7 HLA-B7+ vaccinees had classical CD8 CTL activity detected. However, using both ELISpot and ICS, 8/16 vaccinees (5/7 HLA-B7+) and 0/2 controls had detectable vaccine-specific CD8 T-cell responses. Subjects with moderate or severe systemic or local reactions tended to have more frequent T cell responses and higher antibody responses than those with mild or no reactions. CONCLUSIONS: The severity of local responses related to the formulation of these four peptides in IFA is clinically unacceptable for continued development. Both HIV-specific antibody and T cell responses were induced and the magnitude of response correlated with the severity of local and systemic reactions. If potent adjuvants are necessary for subunit vaccines to induce broad and durable immune responses, careful, incremental clinical evaluation is warranted to minimize the risk of adverse events. TRIAL REGISTRATION: ClinicalTrials.gov NCT00000886

Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella Typhi identifies inter- and intracontinental transmission events.

The emergence of multidrug-resistant (MDR) typhoid is a major global health threat affecting many countries where the disease is endemic. Here whole-genome sequence analysis of 1,832 Salmonella enterica serovar Typhi (S. Typhi) identifies a single dominant MDR lineage, H58, that has emerged and spread throughout Asia and Africa over the last 30 years. Our analysis identifies numerous transmissions of H58, including multiple transfers from Asia to Africa and an ongoing, unrecognized MDR epidemic within Africa itself. Notably, our analysis indicates that H58 lineages are displacing antibiotic-sensitive isolates, transforming the global population structure of this pathogen. H58 isolates can harbor a complex MDR element residing either on transmissible IncHI1 plasmids or within multiple chromosomal integration sites. We also identify new mutations that define the H58 lineage. This phylogeographical analysis provides a framework to facilitate global management of MDR typhoid and is applicable to similar MDR lineages emerging in other bacterial species