Importance of the loading factor in transport CO2 emissions

This paper is focusing on the influence of the loading factor on CO2 emissions, from freight and passengers. A common approach in economics to relate greenhouse gas (GHG) emissions to economic activity is the ASIF model (Unander & Schipper 2000). However, this model has been elaborated for all economic sectors, and it doesn’t take into account the vehicle load factor for the calculation of transport emissions. The objective of this paper is to include the loading factor into the ASIF approach. First, we will include this loading factor into the ASIF equation, aggregating step by step from trip level to macro level; loading will appear as a result of empty running, vehicle capacity and occupancy rate (section 2). Then section 3 will analyse the relationship between loading factor and energy consumption, per type of vehicle. Section 4 will focus on issues concerning freight, as well as section 5 for passengers. The examples will be mainly taken from road transport, which causes most of transport CO2 emissions. Then our conclusion will draw attention on data needs and policy implications

Magnetoelastic coupling and ferromagnetic-type in-gap spin excitations in multiferroic α-Cu2V2O7

We investigate magnetoelectric coupling and low-energy magnetic excitations in multiferroic α-Cu2V2O7 by detailed thermal expansion, magnetostriction, specific heat and magnetization measurements in magnetic fields up to 15 T and by high-field/high-frequency electron spin resonance studies. Our data show negative thermal expansion in the temperature range ≤200 K under study. Well-developed anomalies associated with the onset of multiferroic order (canted antiferromagnetism with a significant magnetic moment and ferroelectricity) imply pronounced coupling to the structure. We detect anomalous entropy changes in the temperature regime up to ∼80 K which significantly exceed the spin entropy. Failure of Grüneisen scaling further confirms that several dominant ordering phenomena are concomitantly driving the multiferroic order. By applying external magnetic fields, anomalies in the thermal expansion and in the magnetization are separated. Noteworthy, the data clearly imply the development of a canted magnetic moment at temperatures above the structural anomaly. Low-field magnetostriction supports the scenario of exchange-striction driven multiferroicity. We observe low-energy magnetic excitations well below the antiferromagnetic gap, i.e., a ferromagnetic-type resonance branch associated with the canted magnetic moment arising from Dzyaloshinsii-Moriya (DM) interactions. The anisotropy parameter meV indicates a sizeable ratio of DM- and isotropic magnetic exchange

Client self-assessment in community aged care: A comparative study involving older Australians and their case managers

Self-assessment of support needs is a relatively new and under-researched phenomenon in domiciliary aged care. This article outlines the results of a comparative study focusing on whether a self-assessment approach assists clients to identify support needs and the degree to which self-assessed needs differ from an assessment conducted by community care professionals. A total of 48 older people and their case managers completed a needs assessment tool. Twenty-two semi-structured interviews were used to ascertain older people’s views and preferences regarding the self-assessment process. The study suggests that while a co-assessment approach as outlined in this article has the potential to assist older people to gain a better understanding of their care needs as well as the assessment process and its ramifications, client self-assessment should be seen as part of a co-assessment process involving care professionals. Such a co-assessment process allows older people to gain a better understanding of their support needs and the wider community aged care context. The article suggests that a co-assessment process involving both clients and care professionals contains features that have the capacity to enhance domiciliary aged care

Blinatumomab compared with standard of care for the treatment of adult patients with relapsed/refractory Philadelphia chromosome–positive B-precursor acute lymphoblastic leukemia

Background: A single-arm, phase 2 trial demonstrated the efficacy and safety of blinatumomab, a bispecific T-cell\u2013engaging antibody construct, in patients with relapsed/refractory (r/r) Philadelphia chromosome\u2013positive (Ph+) acute lymphoblastic leukemia (ALL), a rare hematologic malignancy with limited treatment options. This study compared outcomes with blinatumomab with those of a historical control treated with the standard of care (SOC). Methods: The blinatumomab trial enrolled adult patients with Ph+ ALL who were r/r to at least 1 second-generation tyrosine kinase inhibitor (n = 45). Propensity score analysis (PSA) was used to compare outcomes with blinatumomab with those of an external cohort of similar patients receiving SOC chemotherapy (n = 55). The PSA mitigated confounding variables between studies by adjusting for imbalances in the age at diagnosis and start of treatment, sex, duration from diagnosis to most recent treatment, prior allogeneic hematopoietic stem cell transplantation, prior salvage therapy, and number of salvage therapies. Bayesian data augmentation was applied to improve power to 80% with data from a phase 3 blinatumomab study in r/r Philadelphia chromosome\u2013negative ALL. Results: In the PSA, the rate of complete remission or complete remission with partial hematologic recovery was 36% for blinatumomab and 25% for SOC, and this resulted in an odds ratio of 1.54 (95% confidence interval [CI], 0.61-3.89) or 1.70 (95% credible interval [CrI], 0.94-2.94) with Bayesian data augmentation. Overall survival favored blinatumomab over SOC, with a hazard ratio of 0.81 (95% CI, 0.57-1.14) or 0.77 (95% CrI, 0.61-0.96) with Bayesian data augmentation. Conclusions: These results further support blinatumomab as a treatment option for patients with r/r Ph+ ALL

The Coronae of AR Lac

We observed the coronally active eclipsing binary, AR Lac, with the High Energy Transmission Grating on Chandra for a total of 97 ks, spaced over five orbits, at quadratures and conjunctions. Contemporaneous and simultaneous EUV spectra and photometry were also obtained with the Extreme Ultraviolet Explorer. Significant variability in both X-ray and EUV fluxes were observed, dominated by at least one X-ray flare and one EUV flare. We saw no evidence of primary or secondary eclipses. X-ray flux modulation was largest at high temperature, indicative of flare heating of coronal plasma. Line widths interpreted in terms of Doppler broadening suggest that both binary stellar components are active. From line fluxes obtained from total integrated spectra, we have modeled the emission measure and abundance distributions. A strong maximum was found in the differential emission measure, characterized by peaks at log T = 6.9 and 7.4, together with a weak but significant cooler maximum near log T=6.2, and a moderately strong hot tail from log T= 7.6-8.2. Coronal abundances have a broad distribution and show no simple correlation with first ionization potential. While the resulting model spectrum generally agrees very well with the observed spectrum, there are some significant discrepancies, especially among the many Fe L-lines. Both the emission measure and abundance distributions are qualitatively similar to prior determinations from other X-ray and ultraviolet spectra, indicating some long-term stability in the overall coronal structure.Comment: 31 pages, 8 figures, 3 tables; Accepted for publication in the Astrophysical Journal (tentatively October 1, 2003

Stabilization of protein-protein interactions in drug discovery

Introduction: PPIs are involved in every disease and specific modulation of these PPIs with small molecules would significantly improve our prospects of developing therapeutic agents. Both industry and academia have engaged in the identification and use of PPI inhibitors. However in comparison, the opposite strategy of employing small-molecule stabilizers of PPIs is underrepresented in drug discovery. Areas covered: PPI stabilization has not been exploited in a systematic manner. Rather, this concept validated by a number of therapeutically used natural products like rapamycin and paclitaxel has been shown retrospectively to be the basis of the activity of synthetic molecules originating from drug discovery projects among them lenalidomide and tafamidis. Here, the authors cover the growing number of synthetic small-molecule PPI stabilizers to advocate for a stronger consideration of this as a drug discovery approach. Expert opinion: Both the natural products and the growing number of synthetic molecules show that PPI stabilization is a viable strategy for drug discovery. There is certainly a significant challenge to adapt compound libraries, screening techniques and downstream methodologies to identify, characterize and optimize PPI stabilizers, but the examples of molecules reviewed here in our opinion justify these efforts.</p

Stabilization of protein-protein interactions in drug discovery

Introduction: PPIs are involved in every disease and specific modulation of these PPIs with small molecules would significantly improve our prospects of developing therapeutic agents. Both industry and academia have engaged in the identification and use of PPI inhibitors. However in comparison, the opposite strategy of employing small-molecule stabilizers of PPIs is underrepresented in drug discovery. Areas covered: PPI stabilization has not been exploited in a systematic manner. Rather, this concept validated by a number of therapeutically used natural products like rapamycin and paclitaxel has been shown retrospectively to be the basis of the activity of synthetic molecules originating from drug discovery projects among them lenalidomide and tafamidis. Here, the authors cover the growing number of synthetic small-molecule PPI stabilizers to advocate for a stronger consideration of this as a drug discovery approach. Expert opinion: Both the natural products and the growing number of synthetic molecules show that PPI stabilization is a viable strategy for drug discovery. There is certainly a significant challenge to adapt compound libraries, screening techniques and downstream methodologies to identify, characterize and optimize PPI stabilizers, but the examples of molecules reviewed here in our opinion justify these efforts.</p

Understanding the interaction of 14-3-3 proteins with hDMX and hDM2: a structural and biophysical study

p53 plays a critical role in regulating diverse biological processes: DNA repair, cell cycle arrest, apoptosis, and senescence. The p53 pathway has therefore served as the focus of multiple drug-discovery efforts. p53 is negatively regulated by hDMX and hDM2; prior studies have identified 14-3-3 proteins as hDMX and hDM2 client proteins. 14-3-3 proteins are adaptor proteins that modulate localisation, degradation and interactions of their targets in response to phosphorylation. Thus, 14-3-3 proteins may indirectly modulate the interaction between hDMX or hDM2 and p53 and represent potential targets for modulation of the p53 pathway. In this manuscript, we report on the biophysical and structural characterization of peptide/protein interactions that are representative of the interaction between 14-3-3 and hDMX or hDM2. The data establish that proximal phosphosites spaced ~20-25 residues apart in both hDMX and hDM2 co-operate to facilitate high-affinity 14-3-3 binding and provide structural insight that can be utilized in future stabilizer/inhibitor discovery efforts

Glucocorticoid receptor Thr524 phosphorylation by MINK1 induces interactions with 14-3-3 protein regulators

The glucocorticoid receptor (GR) is a ligand-dependent transcription factor that plays a central role in inflammation. The GR activity is also modulated via protein-protein interactions, including binding of 14-3-3 proteins induced by GR phosphorylation. However, the specific phosphorylation sites on the GR that trigger these interactions and their functional consequences are less clear. Hence, we sought to examine this system in more detail. We used phosphorylated GR peptides, biophysical studies, and X-ray crystallography to identify key residues within the ligand-binding domain of the GR, T524 and S617, whose phosphorylation results in binding of the representative 14-3-3 protein 14-3-3ζ. A kinase screen identified misshapen-like kinase 1 (MINK1) as responsible for phosphorylating T524 and Rho-associated protein kinase 1 for phosphorylating S617; cell-based approaches confirmed the importance of both GR phosphosites and MINK1 but not Rhoassociated protein kinase 1 alone in inducing GR-14-3-3 binding. Together our results provide molecular-level insight into 14-3-3-mediated regulation of the GR and highlight both MINK1 and the GR-14-3-3 axis as potential targets for future therapeutic intervention