The Trans-Pacific Partnership Agreement: Looking Ahead to the Next Steps

Pressure has been building for the conclusion of the 12-country Trans-Pacific Partnership (TPP) negotiations. Getting the deal done is important, but the TPP is not just another free trade agreement (FTA). It represents the chance to set a trade agenda for the future across a wide range of topics for countries throughout the Asia-Pacific region. This means that the agreement should not be settled in haste. More importantly, it also means that key decisions need to be reached about broader issues related to the institutional structure of the TPP. These decisions must be made now, before the deal is closed, on issues such as how to create the TPP as a living agreement, the formation of a TPP Secretariat, and the clarification of entry conditions for future members such as the People’s Republic of China (PRC). These choices must be made deliberately and carefully even while officials are struggling with reaching closure on the most highly sensitive issues still remaining in the agreement. It will not be easy, but wise decisions are necessary now to ensure the long-term success of the TPP

Single Molecule Conformational Memory Extraction: P5ab RNA Hairpin

Extracting kinetic models from single molecule data is an important route to mechanistic insight in biophysics, chemistry, and biology. Data collected from force spectroscopy can probe discrete hops of a single molecule between different conformational states. Model extraction from such data is a challenging inverse problem because single molecule data are noisy and rich in structure. Standard modeling methods normally assume (i) a prespecified number of discrete states and (ii) that transitions between states are Markovian. The data set is then fit to this predetermined model to find a handful of rates describing the transitions between states. We show that it is unnecessary to assume either (i) or (ii) and focus our analysis on the zipping/unzipping transitions of an RNA hairpin. The key is in starting with a very broad class of non-Markov models in order to let the data guide us toward the best model from this very broad class. Our method suggests that there exists a folding intermediate for the P5ab RNA hairpin whose zipping/unzipping is monitored by force spectroscopy experiments. This intermediate would not have been resolved if a Markov model had been assumed from the onset. We compare the merits of our method with those of others

Seismic Fluidization and Foundation Behavior

Field observations of seismic settlements of foundations on granular soils due to shear flow rather than densification or liquefaction are explained in terms of the concept of seismic fluidization. The theory is briefly reviewed and used to derive seismic bearing capacity factors for shallow foundations from the standard static formulas. The reduction of bearing capacity as accelerations increase triggers incremental settlement whenever the ground acceleration exceeds some critical level whose value depends on the static design factor of safety. The total seismic settlement can be computed for a particular earthquake record by a modified sliding block approach or related to standardized incremental displacement curves for generalized earthquakes

Spina bifida-predisposing heterozygous mutations in Planar Cell Polarity genes and Zic2 reduce bone mass in young mice

Fractures are a common comorbidity in children with the neural tube defect (NTD) spina bifida. Mutations in the Wnt/planar cell polarity (PCP) pathway contribute to NTDs in humans and mice, but whether this pathway independently determines bone mass is poorly understood. Here, we first confirmed that core Wnt/PCP components are expressed in osteoblasts and osteoclasts in vitro. In vivo, we performed detailed µCT comparisons of bone structure in tibiae from young male mice heterozygous for NTD-associated mutations versus WT littermates. PCP signalling disruption caused by Vangl2 (Vangl2Lp/+) or Celsr1 (Celsr1Crsh/+) mutations significantly reduced trabecular bone mass and distal tibial cortical thickness. NTD-associated mutations in non-PCP transcription factors were also investigated. Pax3 mutation (Pax3Sp2H/+) had minimal effects on bone mass. Zic2 mutation (Zic2Ku/+) significantly altered the position of the tibia/fibula junction and diminished cortical bone in the proximal tibia. Beyond these genes, we bioinformatically documented the known extent of shared genetic networks between NTDs and bone properties. 46 genes involved in neural tube closure are annotated with bone-related ontologies. These findings document shared genetic networks between spina bifida risk and bone structure, including PCP components and Zic2. Genetic variants which predispose to spina bifida may therefore independently diminish bone mass

Four functional roles for case studies in emerging adulthood research

Case studies have four functional roles which, if more widely embraced, can help to advance theory and methodology in the study of emerging adults. These functions are: case-based theory development, individual-level prediction testing, theory exemplification, and idiographic psychobiography. We describe these functions and provide examples of how each one can add depth, richness and rigour to the burgeoning theory and research on emerging adulthood. We also discuss specifiability (the capacity of a theory to make predictions about, explain and interpret individuals) as a criterion of validity, to be considered as equivalent in status to the external validity criterion of generalizability. Finally we consider the protocols for case study sampling, including intensity sampling, deviant case sampling and significant case sampling

Marking their own homework: The pragmatic and moral legitimacy of industry self-regulation

When is industry self-regulation (ISR) a legitimate form of governance? In principle, ISR can serve the interests of participating companies, regulators and other stakeholders. However, in practice, empirical evidence shows that ISR schemes often under-perform, leading to criticism that such schemes are tantamount to firms marking their own homework. In response, this paper explains how current management theory on ISR has failed to separate the pragmatic legitimacy of ISR based on self-interested calculations, from moral legitimacy based on normative approval. The paper traces three families of management theory on ISR and uses these to map the pragmatic and moral legitimacy of ISR schemes. It identifies tensions between the pragmatic and moral legitimacy of ISR schemes, which the current ISR literature does not address, and draws implications for the future theory and practice of ISR

Exposure of bakery and pastry apprentices to airborne flour dust using PM2.5 and PM10 personal samplers

<p>Abstract</p> <p>Background</p> <p>This study describes exposure levels of bakery and pastry apprentices to flour dust, a known risk factor of occupational asthma.</p> <p>Methods</p> <p>Questionnaires on work activity were completed by 286 students. Among them, 34 performed a series of two personal exposure measurements using a PM_2.5and PM₁₀personal sampler during a complete work shift, one during a cold ("winter") period, and the other during a hot ("summer") period.</p> <p>Results</p> <p>Bakery apprentices experience greater average PM_2.5and PM₁₀exposures than pastry apprentices (p < 0.006). Exposure values for both particulate fractions are greater in winter (average PM₁₀values among bakers = 1.10 mg.m^-3[standard deviation: 0.83]) than in summer (0.63 mg.m^-3[0.36]). While complying with current European occupational limit values, these exposures exceed the ACGIH recommendations set to prevent sensitization to flour dust (0.5 mg.m^-3). Over half the facilities had no ventilation system.</p> <p>Conclusion</p> <p>Young bakery apprentices incur substantial exposure to known airways allergens, a situation that might elicit early induction of airways inflammation.</p