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Carpooling as one of demand management measures is effective in reducing highway congestion. Recent studies have shown that an appropriate spatial allocation of bottleneck capacity between carpool lane and general-purpose lane can lead to peak-spread of the morning commuters' departure time and reduce the system's total trip cost. What is not clear however is whether temporal allocation of bottleneck capacity can also be effective and if so, what the impact would be, and furthermore what the combined effects of temporal-spatial allocation of bottleneck capacity would be. This paper investigates the impacts of a temporal allocation of bottleneck capacity, when carpool lane is available only within a reserved time window, and a joint temporal-spatial capacity allocation, on morning commute patterns. User equilibrium commute patterns are derived for both the temporal-only and the joint temporal-spatial capacity allocation schemes, along a highway corridor with two driving modes: solo driving and carpooling. The extra costs associated with carpooling are considered alongside of travel time and schedule delay costs. We identify three different cases representing the relative barriers and attractions of carpooling to commuters, and we show that the optimal capacity allocations are sensitive to the accurate estimation of the commuters' extra carpool cost. To assist in evaluating the difference between a non-optimal and the optimal temporal-spatial allocation schemes, we derive analytically the upper bounds on the efficiency loss and present numerical illustrations on how the upper bounds vary with the different operational and behavioral variables.

Aims Phenylketonuria (PKU), which is caused by mutations in the phenylalanine hydroxylase (PAH) gene, is one of the most common inherited diseases of amino acid metabolism. Phenylketonuria is characterized by an abnormal accumulation of phenylalanine and its metabolites in body fluids and brain tissues, subsequently leading to severe brain dysfunction. Various pathophysiological and molecular mechanisms underlying brain dysfunction in PKU have been described. However, the metabolic changes and their impacts on the function of cerebral cortices of patients with PKU remain largely unknown. Methods We measured the levels of small molecule metabolites in the cerebrocortical tissues of PKU mice and wild-type control mice using liquid chromatography-mass spectrometry (LC-MS)-based metabolome analysis. Differential metabolites were further subjected to metabolic pathway and enrichment analysis. Results Metabolome analysis revealed 35 compounds among 143 detected metabolites were significantly changed in PKU mice as compared to those in their wild-type littermates. Metabolic pathway and enrichment analysis of these differential metabolites showed that multiple metabolic pathways, including phenylalanine, tyrosine, and tryptophan biosynthesis; valine, leucine, and isoleucine biosynthesis; alanine, aspartate, and glutamate metabolism; purine metabolism; arginine and proline metabolism and methionine metabolism, were impacted in the cerebral cortices of PKU mice. Conclusions The data revealed that multiple metabolic pathways in cerebral cortices of PKU mice were disturbed, suggesting that the disturbances of the metabolic pathways might contribute to neurological or neurodevelopmental dysfunction in PKU, which could thus provide new insights into brain pathogenic mechanisms in PKU as well as mechanistic insights for better understanding the complexity of the metabolic mechanisms of the brain dysfunction in PKU.

OBJECTIVE: To study the association between maternal age and adverse pregnancy outcome in twin pregnancy. METHODS: The clinical data of 2 363 women with twin pregnancy from January 2006 to June 2016 were retrospectively reviewed. According to the age, the women were divided into six groups: < 20 years (n=15), 20-24 years (n=158), 25-29 years (n=894), 30-34 years (n=936), 35-39 years (n=320), and ≥ 40 years group (n=40). The above groups were compared in terms of related baseline features and incidence rates of adverse pregnancy outcomes (preterm birth, birth defect, stillbirth in late pregnancy and small-for-gestational-age birth). A generalized estimating equation was used to investigate the risk of adverse pregnancy outcomes in different age groups. RESULTS: After control for the factors including place of residence, primipara, pregnancy pattern, and gestational diseases, the incidence rates of very preterm birth and moderately preterm birth in the ≥ 40 years group were 2.60 and 1.99 times than those in the 25-29 years group respectively (P < 0.05). The incidence rates of very preterm birth and late preterm birth in the 20-24 years group were 1.99 and 1.33 times than those in the 25-29 years group respectively (P < 0.05). The incidence rates of stillbirth in late pregnancy in the < 20 years group, the 20-24 years group, and the ≥ 40 years group were 9.10, 2.88 and 3.97 times than those in the 25-29 years group respectively (P < 0.05). The incidence rates of small-for-gestational-age birth in the < 20 years group and the 35-39 years group were 2.70 and 0.73 times than those in the 25-29 years group respectively (P < 0.05). CONCLUSIONS: In twin pregnancy, pregnant women, aged < 20 years, have a higher risk of smaller-for-gestational-age birth and stillbirth in late pregnancy, those aged ≥ 40 years have a higher risk of very preterm birth, moderately preterm birth and stillbirth in late pregnancy, and those aged 20-24 years have a higher risk of very preterm birth, late preterm birth and stillbirth in late pregnancy.

The Trans-North China Orogen (TNCO) is well-known as an early Precambrian orogenic belt in the North China Craton (NCC). Three meaningful groups of metamorphic ages have been reported in the metamorphic complexes throughout the TNCO, including c. 1.85 Ga, c. 1.95 Ga, and c. 2.5 Ga. The spatial distributions and relationships of these ages provide notable insight into the formation timing and tectonic evolution of the NCC basement. The Zuoquan and Zanhuang complexes are exposed in the south&ndash, central TNCO and are adjacent to the Eastern Block. In order to place new constraints on the timing of two phases of metamorphism that occurred in the complexes, combined U&ndash, Pb and rare earth element analyses were performed on zircons from different types of metamorphic rocks. Uranium&ndash, Pb zircon dating in this study shows that two groups of metamorphic ages of 1.88&ndash, 1.85 Ga and 2.48&ndash, 2.46 Ga were commonly recorded by metamorphic rocks in the Zanhuang and Zuoquan complexes, respectively. Our previous geochronological studies showed that metamorphic ages of c. 2.51 Ga and c. 1.90 Ga were locally recorded in the Zanhuang and Zuoquan complexes, respectively. These data indicate that metamorphic rocks in the two complexes underwent at least two phases of metamorphism, i.e., 2.51&ndash, 2.46 Ga (Phase I) and 1.90&ndash, 1.85 Ga (Phase II). In combination with previous studies regarding reaction microstructures, metamorphic pressure&ndash, temperature paths, and geochronology, the Phase II metamorphic ages are interpreted to be linked to the collision between the Western and Eastern Blocks along the TNCO between 1.97 Ga and 1.80 Ga, whereas the Phase I metamorphic ages, as a result of an earlier and extensive tectono-thermal event that occurred in the Eastern and Western Blocks of the NCC, were related to underplating of mantle-derived magma. It is inferred that the rocks with c. 2.51&ndash, 2.46 Ga metamorphic ages in the two complexes formed in the Eastern Block and underwent regional metamorphism during that period, and then were tectonically involved in the TNCO and experienced c. 1.90&ndash, 1.85 Ga metamorphism. Metamorphic peaks occurred at different crustal levels in the orogen, resulting in distinct metamorphic ages and peak conditions preserved by metamorphic rocks in the two complexes.

Aims Phenylketonuria (PKU), which is caused by mutations in the phenylalanine hydroxylase (PAH) gene, is one of the most common inherited diseases of amino acid metabolism. Phenylketonuria is characterized by an abnormal accumulation of phenylalanine and its metabolites in body fluids and brain tissues, subsequently leading to severe brain dysfunction. Various pathophysiological and molecular mechanisms underlying brain dysfunction in PKU have been described. However, the metabolic changes and their impacts on the function of cerebral cortices of patients with PKU remain largely unknown. Methods We measured the levels of small molecule metabolites in the cerebrocortical tissues of PKU mice and wild‐type control mice using liquid chromatography‐mass spectrometry (LC‐MS)‐based metabolome analysis. Differential metabolites were further subjected to metabolic pathway and enrichment analysis. Results Metabolome analysis revealed 35 compounds among 143 detected metabolites were significantly changed in PKU mice as compared to those in their wild‐type littermates. Metabolic pathway and enrichment analysis of these differential metabolites showed that multiple metabolic pathways, including phenylalanine, tyrosine, and tryptophan biosynthesis; valine, leucine, and isoleucine biosynthesis; alanine, aspartate, and glutamate metabolism; purine metabolism; arginine and proline metabolism and methionine metabolism, were impacted in the cerebral cortices of PKU mice. Conclusions The data revealed that multiple metabolic pathways in cerebral cortices of PKU mice were disturbed, suggesting that the disturbances of the metabolic pathways might contribute to neurological or neurodevelopmental dysfunction in PKU, which could thus provide new insights into brain pathogenic mechanisms in PKU as well as mechanistic insights for better understanding the complexity of the metabolic mechanisms of the brain dysfunction in PKU.

In this paper we investigate a bottleneck model in which the capacity of the bottleneck is assumed stochastic and follows a uniform distribution. The commuters' departure time choice is assumed to follow the user equilibrium principle according to mean trip cost. The analytical solution of the proposed model is derived. Both the analytical and numerical results show that the capacity variability would indeed change the commuters' travel behavior by increasing the mean trip cost and lengthening the peak period. We then design congestion pricing schemes within the framework of the new stochastic bottleneck model, for both a time-varying toll and a single-step coarse toll, and prove that the proposed piecewise time-varying toll can effectively cut down, and even eliminate, the queues behind the bottleneck. We also find that the single-step coarse toll could either advance or postpone the earliest departure time. Furthermore, the numerical results show that the proposed pricing schemes can indeed improve the efficiency of the stochastic bottleneck through decreasing the system’s total travel cost.

This paper investigates the impact of stochastic capacity at the downstream bottleneck after a merge and the impact of merging behavior on the morning commuters’ departure-time patterns. The classic bottleneck theory is extended to include a uniformly distributed capacity and the commuters’ equilibrium departure patterns are derived for two different merging rules. The results show that uncertainty in the bottleneck capacity increases the commuters’ mean trip cost and lengthens the peak period, and that the system total cost is lower under give-way merging than under a fixed-rate merging. Capacity paradoxes with dynamic user responses are found under both merging rules.

This article proposes a tradable credit scheme for managing commuters’ travel choices. The scheme considers bottleneck congestion and modal split in a competitive highway–transit network with heterogeneous commuters who are distinguished by their valuation of travel time. The scheme charges all auto travelers who pass the bottleneck during a peak-time window in the form of mobility credits. Those who avoid the peak-time window, by either traveling outside the peak-time window or switching to the transit mode, may be rewarded credits. An artificial market is created so that the travelers may trade these credits with each other. We formulate the credit price and the rewarded and charged credits under tradable credit scheme. Our analyses indicate that the optimal tradable credit scheme can achieve nearly 40% efficiency gains depending on the level of commuters’ heterogeneity. In addition, this scheme distributes the benefits among all the commuters directly through the credit trading. Our results suggest that in assessing the efficiency of tradable credit scheme, it is important to take into account the commuters’ heterogeneity. Numerical experiments are conducted to examine the sensitivity of tradable credit scheme designs to various system parameters.

This paper extends the bottleneck model to study congestion behavior of morning commute with flexible work schedule. The proposed model assumes a stochastic bottleneck capacity which follows a uniform distribution and homogeneous commuters who have the same preferred arrival time interval. The commuters are fully aware of the stochastic properties of travel time and schedule delay distributions at all departure times that emerge from day-to-day capacity variations. The commuters’ departure time choice follows user equilibrium (UE) principle in terms of the expected trip cost. Analytical and numerical solutions of this model are provided. The equilibrium departure time patterns are examined which show that the stochastic capacity increases the mean trip cost and lengthens the rush hour. The adoption of flexitime results in less congestion and more efficient use of bottleneck capacity than fixed-time work schedule. The longer the flexi-time interval is, the more uniformly distributed the departure times are.