Ambiguities in order-theoretic formulations of thermodynamics

Since the 1909 work of Carath\'eodory, formulations of thermodynamics have gained ground which highlight the role of the the binary relation of adiabatic accessibility between equilibrium states. A feature of Carath\'eodory's system is that the version therein of the second law contains an ambiguity about the nature of irreversible adiabatic processes, making it weaker than the traditional Kelvin-Planck statement of the law. This paper attempts first to clarify the nature of this ambiguity, by defining the arrow of time in thermodynamics by way of the Equilibrium Principle ("Minus First Law"). It then argues that the ambiguity reappears in the important 1999 axiomatisation due to Lieb and Yngvason.Comment: 13 pages, 1 figur

Reductions in disease activity in the AMPLE trial: clinical response by baseline disease duration

Objectives: To evaluate clinical response by baseline disease duration using 2-year data from the AMPLE trial. Methods: Patients were randomised to subcutaneous abatacept 125 mg weekly or adalimumab 40 mg biweekly, with background methotrexate. As part of a post hoc analysis, the achievement of validated definitions of remission (Clinical Disease Activity Index (CDAI) ≤2.8, Simplified Disease Activity Index (SDAI) ≤3.3, Routine Assessment of Patient Index Data 3 (RAPID3) ≤3.0, Boolean score ≤1), low disease activity (CDAI \u3c10, SDAI \u3c11, RAPID3 ≤6.0), Health Assessment Questionnaire-Disability Index response and American College of Rheumatology responses were evaluated by baseline disease duration (≤6 vs \u3e6 months). Disease Activity Score 28 (C-reactive protein) \u3c2.6 or ≤3.2 and radiographic non-progression in patients achieving remission were also evaluated. Results: A total of 646 patients were randomised and treated (abatacept, n=318; adalimumab, n=328). In both treatment groups, comparable responses were achieved in patients with early rheumatoid arthritis (≤6 months) and in those with later disease (\u3e6 months) across multiple clinical measures Conclusions: Abatacept or adalimumab with background methotrexate were associated with similar onset and sustainability of response over 2 years. Patients treated early or later in the disease course achieved comparable clinical responses

Proteome and phosphoproteome analysis of brown adipocytes reveals that RICTOR loss dampens global insulin/AKT signaling

Stimulating brown adipose tissue (BAT) activity represents a promising therapy for overcoming metabolic diseases. mTORC2 is important for regulating BAT metabolism, but its downstream targets have not been fully characterized. In this study, we apply proteomics and phosphoproteomics to investigate the downstream effectors of mTORC2 in brown adipocytes. We compare wild-type controls to isogenic cells with an induced knockout of the mTORC2 subunit RICTOR (Rictor-iKO) by stimulating each with insulin for a 30-minute time course. In Rictor-iKO cells, we identify decreases to the abundance of glycolytic and de novo lipogenesis enzymes, and increases to mitochondrial proteins as well as a set of proteins known to increase upon interferon stimulation. We also observe significant differences to basal phosphorylation due to chronic RICTOR loss including decreased phosphorylation of the lipid droplet protein perilipin-1 in Rictor-iKO cells, suggesting that RICTOR could be involved with regulating basal lipolysis or droplet dynamics. Finally, we observe mild dampening of acute insulin signaling response in Rictor-iKO cells, and a subset of AKT substrates exhibiting statistically significant dependence on RICTOR.Fil: Entwisle, Samuel W.. University of Washington; Estados UnidosFil: Martinez Calejman, Camila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Valente, Anthony S.. University of Washington; Estados UnidosFil: Lawrence, Robert T.. University of Washington; Estados UnidosFil: Hung, Chien Min. University Of Massachussets. Medical School; Estados UnidosFil: Guertin, David A.. University Of Massachussets. Medical School; Estados UnidosFil: Villen, Judit. University of Washington; Estados Unido

Toll-Like Receptor 7 Stimulates the Expression of Epstein-Barr Virus Latent Membrane Protein 1

Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus. Toll-like receptor 7 (TLR7) is involved in host innate immunity against pathogens, and its aberrant activation is linked to the development of systemic lupus erythematosus (SLE, also called ‘‘lupus’’). Type I interferons (IFN) are apparently driving forces for lupus pathogenesis. Previously, we found that EBV latent membrane protein 1 (LMP1) primes cells for IFN production. In this report, the relationship among EBV LMP1, TLRs, and IFN production are examined. We find that TLR7 activation increases the expression of EBV LMP1, and IFN regulatory factor 7 (IRF7) is involved in the stimulation process. TLR7 activation did not induce IFNs from EBV-infected cells, but potentiates those cells for IFN production by TLR3 or TLR9 activation. In addition, we find that LMP1 and IFNs are coexpressed in the same cells in some lupus patients. Therefore, the aberrant activation of TLR7 might induce LMP1 expression and LMP1-expression cells may be producing IFNs in lupus patients. These results suggest EBV might be an exacerbating factor in some lupus patients via promoting IFN production

Estudo de biofilmes de kefir associado com gérmen de soja (Glycine max (L.) Merril)

The aim of this study was to investigate biofilm formation with kefir grains in the presence of soy extract. Kefir grains and soy germs at different concentrations were grown in the culture medium comprising brown sugar solution (40 gl-1) for 20 days. Biofilms that formed in this period were then removed and the pH of the culture medium were measured. Isoflavones of the medium of culture were extracted and quantified by high-performance liquid chromatography (HPLC). The superficial properties of the selected biofilms were analyzed by atomic force microscopy (AFM) and scanning electron microscopy (SEM). The culture medium after 20 days was found to have 19.59±3.57 µgl-1 of glycitein and 23.86±2.21 µgl-1 of genistein. The best concentration of kefir grains in order to extract isoflavone was 40 gl-1, with yield levels at 11.67 µgl-1 of glycitein and 17.78 µgl-1 of genistein. The analysis by AFM and SEM confirmed the increased roughness of the biofilm, dependent of the concentration of the amount of kefir grains. It is suggested that the biofilms incorporated the isoflavones and has potential for therapeutic applications in several pathologies wherein it is necessary the antioxidative processes.O principal objetivo deste estudo foi investigar a formação de biofilme com grãos de kefir na presença de extrato de soja. Diferentes concentrações de grãos de kefir e de gérmen de soja foram cultivados em meio de cultura constituido de solução de acúcar mascavo (40 gl-1) durante 20 dias. Os biofilmes formados neste período foram então removidos tendo sido determinado o pH do meio de cultura. As isoflavonas do meio de cultura foram extraidas e quantificadas por Cromotografia Líquida de Alta Perfomance (CLAP).  As propriedades superficiais dos biofilmes selecionados foram analisadas por microscopia de força atômica (AFM) e microscopia eletrônica de varredura (MEV). O meio de cultura após 20 dias apresentou 19,59±3,57 µgl-1 de gliciteína e 23,86±2,21 µgl-1 de genisteína. A melhor concentração de grãos de kefir para extração de isoflavona foi de 40 gl-1, com níveis de rendimento de 11,67 µgl-1 de gliciteína e 17,78 µgl-1 de genisteína. A análise por AFM e MEV confirmou o aumento da rugosidade do biofilme, dependente da concentração da quantidade de grãos de kefir. Sugere-se que os biofilmes incorporam as isoflavonas e tem potencial para aplicações terapêuticas em diversas patologias em que se faz necessário os processos antioxidantes

Interpreting syndepositional sediment remobilization and deformation beneath submarine gravity flows; a kinematic boundary layer approach

Turbidite sandstones and related deposits commonly contain deformation structures and remobilized sediment that might have resulted from post-depositional modification such as downslope creep (e.g. slumping) or density-driven loading by overlying deposits. However, we consider that deformation can occur during the passage of turbidity currents that exerted shear stress on their substrates (whether entirely pre-existing strata, sediment deposited by earlier parts of the flow itself or some combination of these). Criteria are outlined here, to avoid confusion with products of other mechanisms (e.g. slumping or later tectonics), which establish the synchronicity between the passage of overriding flows and deformation of their substrates. This underpins a new analytical framework for tracking the relationship between deformation, deposition and the transit of the causal turbidity current, through the concept of kinematic boundary layers. Case study examples are drawn from outcrop (Miocene of New Zealand, and Apennines of Italy) and subsurface examples (Britannia Sandstone, Cretaceous, UK Continental Shelf). Example structures include asymmetric flame structures, convolute lamination, some debritic units and injection complexes, together with slurry and mixed slurry facies. These structures may provide insight into the rheology and dynamics of submarine flows and their substrates, and have implications for the development of subsurface turbidite reservoirs

Quantitative definition and monitoring of the host cell protein proteome using iTRAQ: a study of an industrial mAb producing CHO-S cell line

There are few studies defining CHO host cell proteins (HCPs) and the flux of these throughout a downstream purification process. Here we have applied quantitative iTRAQ proteomics to follow the HCP profile of an antibody (mAb) producing CHO-S cell line throughout a standard downstream purification procedure consisting of a Protein A, cation and anion exchange process. We used both 6 sample iTRAQ experiment to analyze technical replicates of three samples, which were culture harvest (HCCF), Protein A flow through and Protein A eluate and an 8 sample format to analyze technical replicates of four sample types; HCCF compared to Protein A eluate and subsequent cation and anion exchange purification. In the 6 sample iTRAQ experiment, 8781 spectra were confidently matched to peptides from 819 proteins (including the mAb chains). Across both the 6 and 8 sample experiments 936 proteins were identified. In the 8 sample comparison, 4187 spectra were confidently matched to peptides from 219 proteins. We then used the iTRAQ data to enable estimation of the relative change of individual proteins across the purification steps. These data provide the basis for application of iTRAQ for process development based upon knowledge of critical HCPs