Integrated Optimization of Transit Networks with Schedule- and Frequency-Based Services Subject to the Bounded Stochastic User Equilibrium

In many European metropolitan areas, the urban transit system is a mixture of schedule- and frequency-based services. This study proposes an integrated transit frequency and schedule design problem (ITFSDP), where frequencies and schedules are simultaneously determined, and develops a biobjective model for the ITFSDP to minimize operation costs and total passenger-perceived generalized travel cost. Meanwhile, the passengers' route choice behavior is described by the bounded stochastic user equilibrium (BSUE). The in-vehicle congestion effect is represented using a set of constraints that differ in terms of the sitting and standing costs as sitting and standing passengers perceive crowding differently. This set of constraints captures the realistic behavioral feature that having occupied a seat, users remain seated at subsequent stops in the same vehicle. The problem is formulated as a mixed integer nonlinear programming problem, which is subsequently linearized to a mixed integer linear programming problem and solved using a branch and bound algorithm. A column generation and reduction phase is embedded in the solution algorithm to obtain the bounded choice set according to the BSUE constraints. Experiments are conducted to illustrate the model's properties and the performance of the solution method. In particular, we demonstrate a Braess-like paradoxical phenomenon in the context of transit scheduling and highlight that well-synchronized transit services can deteriorate the network performance in terms of the total passengers' generalized travel cost when considering passenger congestion costs because of crowding

Angiogenesis PET Tracer Uptake (⁶⁸Ga-NODAGA-E[(cRGDyK)]₂) in Induced Myocardial Infarction and Stromal Cell Treatment in Minipigs

Angiogenesis is considered integral to the reparative process after ischemic injury. The αvβ3 integrin is a critical modulator of angiogenesis and highly expressed in activated endothelial cells. 68Ga-NODAGA-E[(cRGDyK)]2 (RGD) is a positron-emission-tomography (PET) ligand targeted towards αvβ3 integrin. The aim was to present data for the uptake of RGD and correlate it with histology and to further illustrate the differences in angiogenesis due to porcine adipose-derived mesenchymal stromal cell (pASC) or saline treatment in minipigs after induction of myocardial infarction (MI). Three minipigs were treated with direct intra-myocardial injection of pASCs and two minipigs with saline. MI was confirmed by 82Rubidium (82Rb) dipyridamole stress PET. Mean Standardized Uptake Values (SUVmean) of RGD were higher in the infarct compared to non-infarct area one week and one month after MI in both pASC-treated (SUVmean: 1.23 vs. 0.88 and 1.02 vs. 0.86, p < 0.05 for both) and non-pASC-treated minipigs (SUVmean: 1.44 vs. 1.07 and 1.26 vs. 1.04, p < 0.05 for both). However, there was no difference in RGD uptake, ejection fractions, coronary flow reserves or capillary density in histology between the two groups. In summary, indications of angiogenesis were present in the infarcted myocardium. However, no differences between pASC-treated and non-pASC-treated minipigs could be demonstrated

Release of lead from Renaissance lead-glazed ceramics from southern Denmark and northern Germany: Implications from acetic acid etching

Lead-glazed potsherds from archaeological excavations at six Renaissance (1536–1660 CE) sites in southern Denmark and northern Germany have been subjected to etching experiments using 4 wt% acetic acid. The extracts of 45 sherds were analysed by Inductively Coupled Plasma Mass Spectrometry. At one site, the ducal hunting castle of Grøngaard, Pb levels in acid extracts from glazed dishes were so high (up to 29,000 µg Pb cm−2 day−1) that acute toxic effects likely occurred if the dishes were used for serving food containing vinegar. More moderate acid-etching Pb levels were found in dishes from other sites, but they still exceed the WHO critical level if used daily. Acetic acid etching experiments performed on pipkins (three-legged cooking pots with a handle) yielded somewhat lower Pb extract values, averaging ca. 25 µg Pb cm−2 day−1. Taking into account the widespread use of pipkins for cooking, they might easily have led to a higher weekly Pb intake than the use of the moderate-level dishes. The question remains whether such high levels of Pb exposure during meals led to injurious Pb intake. Prior skeletal analyses have shown that medieval to early modern individuals from the area, especially in towns, were exposed to Pb. While exposure could have come from various sources other than lead-glazed ceramics, such as cosmetics, paint, antibacterial ointments, and lead water pipes, widely distributed lead-glazed ceramics had the potential of being a main source of Pb. How the pottery was actually used is uncertain, and it certainly was not evenly distributed across all segments of society, but the etching experiment results suggest that severe poisonous effects could have resulted from the use of lead-glazed Renaissance ceramics

Greenland records of aerosol source and atmospheric lifetime changes from the Eemian to the Holocene.

The Northern Hemisphere experienced dramatic changes during the last glacial, featuring vast ice sheets and abrupt climate events, while high northern latitudes during the last interglacial (Eemian) were warmer than today. Here we use high-resolution aerosol records from the Greenland NEEM ice core to reconstruct the environmental alterations in aerosol source regions accompanying these changes. Separating source and transport effects, we find strongly reduced terrestrial biogenic emissions during glacial times reflecting net loss of vegetated area in North America. Rapid climate changes during the glacial have little effect on terrestrial biogenic aerosol emissions. A strong increase in terrestrial dust emissions during the coldest intervals indicates higher aridity and dust storm activity in East Asian deserts. Glacial sea salt aerosol emissions in the North Atlantic region increase only moderately (50%), likely due to sea ice expansion. Lower aerosol concentrations in Eemian ice compared to the Holocene are mainly due to shortened atmospheric residence time, while emissions changed little.NEEM is directed and organized by the Center of Ice and Climate at the Niels Bohr Institute and US NSF, Office of Polar Programs. It is supported by funding agencies and institutions in Belgium (FNRS-CFB and FWO), Canada (NRCan/GSC), China (CAS), Denmark (FIST), France (IPEV, CNRS/INSU, CEA and ANR), Germany (AWI), Iceland (RannIs), Japan (NIPR), Korea (KOPRI), The Netherlands (NWO/ALW), Sweden (VR), Switzerland (SNF), United Kingdom (NERC), and the USA (US NSF, Office of Polar Programs). Long-term support of ice core research at the University of Bern by SNF is gratefully acknowledged

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)