The Response of Prices, Sales, and Output to Temporary Changes in Demand

We determine empirically how the Big Three automakers accommodate shocks to demand. They have the capability to change prices, alter labor inputs through temporary layoffs and overtime, or adjust inventories. These adjustments are interrelated, non-convex, and dynamic in nature. Combining weekly plant-level data on production schedules and output with monthly data on sales and transaction prices, we estimate a dynamic profit-maximization model of the firm. Using impulse response functions, we demonstrate that when an automaker is hit with a demand shock sales respond immediately, prices respond gradually, and production responds only after a delay. The size of the immediate sales response is linear in the size of the shock, but the delayed production response is non-convex in the size of the shock. For sufficiently large shocks the cumulative production response over the product cycle is an order of magnitude larger than the cumulative price response. We examine two recent demand shocks: the Ford Explorer/Firestone tire recall of 2000, and the September 11, 2001 terrorist attacks

The Worlds of Splicing and Chromatin Collide

Both transcription and splicing take place in a nuclear environment which, at face value, may seem refractory to the efficiency afforded by the coupling of both processes. This environment, chromatin, was once viewed as only a passive packaging system for genetic material, with very little contribution to the variety of nuclear activities occurring within and around it. However, overwhelming evidence now points to the chromatin environment as being highly dynamic, and an active player in nuclear activities

Reprint of “Pharmacokinetic modelling of the anti-malarial drug artesunate and its active metabolite dihydroartemisinin”

A four compartment mechanistic mathematical model is developed for the pharmacokinetics of the commonly used anti-malarial drug artesunate and its principle metabolite dihydroartemisinin following oral administration of artesunate. The model is structurally unidentifiable unless additional constraints are imposed. Combinations of mechanistically derived constraints are considered to assess their effects on structural identifiability and on model fits. Certain combinations of the constraints give rise to locally or globally identifiable model structures. Initial validation of the model under various combinations of the constraints leading to identifiable model structures was performed against a dataset of artesunate and dihydroartemisinin concentration–time profiles of 19 malaria patients. When all the discussed constraints were imposed on the model, the resulting globally identifiable model structure was found to fit reasonably well to those patients with normal drug absorption profiles. However, there is wide variability in the fitted parameters and further investigation is warranted

Gendered Races: Implications for Interracial Marriage, Leadership Selection, and Athletic Participation

Six studies explored the overlap between racial and gender stereotypes and the consequences of this overlap for interracial dating, leadership selection, and athletic participation. Two initial studies, utilizing explicit and implicit measures, captured the stereotype content of different racial groups: the Asian stereotype was seen as more feminine whereas the Black stereotype more masculine compared to the White stereotype. Study 3 found that preferences for masculinity versus femininity mediated White participants' attraction to Blacks relative to Asians. Analysis of the 2000 United States Census replicated this pattern with interracial marriages. In Study 5, Blacks were more likely and Asians less likely to be selected for a masculine leadership position compared to Whites. Study 6 analyzed the NCAA Student-Athlete Ethnicity Report and found Blacks were more heavily represented in masculine versus feminine sports relative to Asians. These studies demonstrate that the association between racial and gender stereotypes has important real-world consequences

Structural and statistical aspects in joint modelling of artesunate pharmacometrics and malarial parasite lifecycle

Malaria is a parasite with a complex lifecycle, and commonly used antimalarial agents from the artemisinin family have varied effectiveness over different stages of this lifecycle. The pharmacokinetic profile of the artemisinins is also strongly influenced by the parasite burden and lifecycle stage. This work introduces a new pharmacokinetic and pharmacodynamic model incorporating these interdependent drug and lifecycle features, for orally administered artesunate and its principal metabolite dihydroartemisinin. This model, like the underlying system whose features it attempts to capture, is quite complex and cannot be solved analytically like standard linear first-order compartmental models previously used for pharmacokinetic modelling of these drugs. Therefore, understanding, inference and validity are explored through use of the modern statistical technique of a Sequential Monte Carlo sampler. Structural, numerical and practical identifiability are important concepts for all models, the latter two especially so in this case as the model structure does not admit an algebraic structural identifiability analysis. Motivated by this, the above identifiability concepts are also investigated in connection with the Sequential Monte Carlo technique. Sequential Monte Carlo is demonstrated to be a useful tool for gaining insight into models whose structural identifiability is not known, just as it is also shown to have significant advantages in parameter inference over the classical approach. The coupled parasite lifecycle and artemisinin-derivative model is built in stages, starting with an in vitro submodel capturing the dynamics of uptake of artemisinins into parasitised and non-parasitised red blood cells. Next, the parasite lifecycle, or ‘ageing’ model, is introduced, which uses a new concept of shadow compartments to achieve its aims of describing ageing in continuous time and to exhibit sufficient control over the parasite population. Finally, these models are integrated together into the full coupled pharmacokinetic and pharmacodynamic model. More work is needed to fully assess the resultant model on clinical datasets, but the building blocks upon which it was constructed appear to fulfil their aims reasonably well

Experimental measurement-device-independent verification of quantum steering

Bell non-locality between distant quantum systems-that is, joint correlations which violate a Bell inequality-can be verified without trusting the measurement devices used, nor those performing the measurements. This leads to unconditionally secure protocols for quantum information tasks such as cryptographic key distribution. However, complete verification of Bell non-locality requires high detection efficiencies, and is not robust to typical transmission losses over long distances. In contrast, quantum or Einstein-Podolsky-Rosen steering, a weaker form of quantum correlation, can be verified for arbitrarily low detection efficiencies and high losses. The cost is that current steering-verification protocols require complete trust in one of the measurement devices and its operator, allowing only one-sided secure key distribution. Here we present measurement-device-independent steering protocols that remove this need for trust, even when Bell non-locality is not present. We experimentally demonstrate this principle for singlet states and states that do not violate a Bell inequality.Australian Research Council/140100648Marie-Curie Fellowshi

Post-transcriptional regulation of satellite cell quiescence by TTP-mediated mRNA decay.

Skeletal muscle satellite cells in their niche are quiescent and upon muscle injury, exit quiescence, proliferate to repair muscle tissue, and self-renew to replenish the satellite cell population. To understand the mechanisms involved in maintaining satellite cell quiescence, we identified gene transcripts that were differentially expressed during satellite cell activation following muscle injury. Transcripts encoding RNA binding proteins were among the most significantly changed and included the mRNA decay factor Tristetraprolin. Tristetraprolin promotes the decay of MyoD mRNA, which encodes a transcriptional regulator of myogenic commitment, via binding to the MyoD mRNA 3' untranslated region. Upon satellite cell activation, p38α/β MAPK phosphorylates MAPKAP2 and inactivates Tristetraprolin, stabilizing MyoD mRNA. Satellite cell specific knockdown of Tristetraprolin precociously activates satellite cells in vivo, enabling MyoD accumulation, differentiation and cell fusion into myofibers. Regulation of mRNAs by Tristetraprolin appears to function as one of several critical post-transcriptional regulatory mechanisms controlling satellite cell homeostasis

A Global Climatology of Extratropical Transition. Part I: Characteristics across Basins

The authors present a global climatology of tropical cyclones (TCs) that undergo extratropical transition (ET). ET is objectively defined based on a TC’s trajectory through the cyclone phase space (CPS), which is calculated using storm tracks from 1979–2017 best track data and geopotential height fields from reanalysis datasets. Two reanalyses are used and compared for this purpose, the Japanese 55-yr Reanalysis and the ECMWF interim reanalysis. The results are used to study the seasonal and geographical distributions of storms undergoing ET and interbasin differences in the statistics of ET occurrence. About 50% of all TCs in the North Atlantic and the western North Pacific undergo ET. In the Southern Hemisphere, ET fractions range from about 20% in the south Indian Ocean and the Australian region to 45% in the South Pacific. In the majority of ETs, TCs become thermally asymmetric before forming a cold core. However, a substantial fraction of TCs take the reverse pathway, developing a cold core before becoming thermally asymmetric. This pathway is most common in the eastern North Pacific and the North Atlantic. Different ET pathways can be linked to different geographical trajectories and environmental settings. In ETs over warmer sea surface temperatures, TCs tend to lose their thermal symmetry while still maintaining a warm core. Landfalls by TCs undergoing ET occur 3–4 times per year in the North Atlantic and 7–10 times per year in the western North Pacific, while coastal regions in the Australian region are affected once every 1–2 years