Pharmaceutical distribution routing problem is a key problem for pharmaceutical enterprises, since efficient schedules can enhance resource utilization and reduce operating costs. Meanwhile, it is a complicated combinatorial optimization problem. Existing research mainly focused on delivery route lengths or distribution costs minimization, while seldom considered customer priority and carbon emissions simultaneously. However, considering the customer priority and carbon emissions simultaneously will not only help to enhance customer satisfaction, but also help to reduce the carbon emissions. In this article, we consider the customer priority and carbon emission minimization simultaneously in the pharmaceutical distribution routing problem, the corresponding problem is named pharmaceutical distribution routing problem considering customer priority and carbon emissions. A corresponding mathematical model is formulated, the objectives of which are minimizing fixed cost, refrigeration cost, fuel consumption cost, carbon emission cost, and penalty cost for violating time windows. Moreover, a hybrid genetic algorithm (HGA) is proposed to solve the problem. The framework of the proposed HGA is genetic algorithm (GA), where an effective local search based on variable neighborhood search (VNS) is specially designed and incorporated to improve the intensification abilities. In the proposed HGA, crossover with adaptive probability and mutation with adaptive probability are utilized to enhance the algorithm performance. Finally, the proposed HGA is compared with four optimization algorithms, and experimental results have demonstrated the effectiveness of the HGA.

Zygotic genome activation (ZGA) is a critical event in early embryonic development, and thousands of genes are involved in this delicate and sophisticated biological process. To date, however, only a handful of these genes have revealed their core functions in this special process, and therefore the roles of other genes still remain unclear. In the present study, we used previously published transcriptome profiling to identify potential key genes (candidate genes) in minor ZGA and major ZGA in both human and mouse specimens, and further identified the conserved genes across species. Our results showed that 887 and 760 genes, respectively, were thought to be specific to human and mouse in major ZGA, and the other 135 genes were considered to be orthologous genes. Moreover, the conserved genes were most enriched in rRNA processing in the nucleus and cytosol, ribonucleoprotein complex biogenesis, ribonucleoprotein complex assembly and ribosome large subunit biogenesis. The findings of this first comprehensive identification and characterization of candidate genes in minor and major ZGA provide relevant insights for future studies on ZGA.

A high-energy, alignment-insensitive, injection-seeded Q-switched Ho:yttrium aluminum garnet (YAG) single-frequency laser is developed. Both the slave Q-switched laser and the seed laser are Ho:YAG ring lasers based on a pair of corner cubic reflectors. The seed laser has an available power of 830 mW at 2096.667 nm. At 100 Hz, the Q-switched Ho:YAG laser provides a single-frequency pulsed output using injection-seeded technology. The 7.3 mJ single-frequency pulse energy from the slave laser has a pulse width of 161.2 ns and is scaled to 33.3 mJ after passing through the Ho:YAG single-pass amplifier. According to the measurement results of the heterodyne beating technique, the single-frequency pulse has a half-width of 4.12 MHz.

The rearrangement of drainage basins provides critical insight into crustal deformation and geodynamic mechanisms. Near the southeastern boundary of the Tibetan Plateau, the Dadu River abruptly shifts from south- to east-flowing, providing important implications for regional tectonogeomorphic development since the mid-Pleistocene. South of the bend, the headwaters of the Anning River occupy an unusually wide valley. Field investigations show that large quantities of fluvial/lacustrine sediments are widespread along the Dadu and Anning rivers and are exposed at their drainage divide. Detrital zircon U-Pb age patterns confirm that these fluvial/lacustrine sediments are the remnants of the paleo-Dadu River, which strongly suggests that the paleo-Dadu River originally flowed southward into the Anning River. The cosmogenic nuclide burial ages of the lacustrine sediments along the Dadu and Anning rivers suggest deposition of these sediments from separate dammed lakes ca. 1.2 Ma ago, ca. 0.6 Ma ago, and ca. 0.9 Ma ago from north to south, respectively. Provenance and burial-age studies indicate that reorganization of the Dadu drainage occurred within the last 0.6 Ma. We propose that this drainage reorganization in southeastern Tibet resulted from progressive convergence between the India and Eurasian plates during the Pleistocene.

Hyperinsulinaemia and insulin resistance have been proposed to be associated with mortality risk, and diet can modulate insulin response. However, whether dietary patterns with high insulinaemic potential are associated with mortality remains unknown. We prospectively examined the associations between hyperinsulinaemic diets and the risk of total and cause-specific mortality in a large nationally representative population. Dietary factors were assessed by 24-h recalls. Two empirical dietary indices for hyperinsulinaemia (EDIH) and insulin resistance (EDIR) were developed to identify food groups most predictive of biomarkers for hyperinsulinaemia (C-peptide and insulin) and insulin resistance (homoeostatic model assessment for insulin resistance), respectively. Deaths from date of the first dietary interview until 31 December 2015 were identified by the National Death Index. Multivariable hazard ratios (HR) and 95 % CI were calculated using Cox regression models. During a median follow-up of 7·8 years, 4904 deaths were documented among 40 074 participants. For EDIH, the multivariable-adjusted HR (comparing extreme quintiles) were 1·20 (95 % CI 1·09, 1·32, P-trend<0·001) for overall mortality and 1·41 (95 % CI 1·15, 1·74, P-trend = 0·002) for CVD mortality. Similar associations were observed for EDIR with HR of 1·18 (95 % CI 1·07, 1·29, P-trend < 0·001) for total and 1·35 (95 % CI 1·09, 1·67, P-trend = 0·005) for CVD mortality. After further adjustments for BMI and diabetes, these positive associations were somewhat attenuated. Our findings suggested that diets with higher insulinaemic potential are associated with increased risk of overall and CVD-specific mortality.

Inflammation is a central mechanism in metabolic disorders associated with morbidity and mortality and dietary factors can modulate inflammation. We aimed to prospectively investigate the association between an empirically developed, food-based dietary inflammatory pattern (EDIP) score and the risk of overall and cause-specific mortality, using data from the US National Health and Nutrition Examination Survey from 1999 to 2014. EDIP score was derived by entering thirty-nine predefined commonly consumed food groups into the reduced rank regression models followed by stepwise linear regression, which was most predictive of two plasma inflammation biomarkers including C-reactive protein and leucocyte count among 25 500 US adults. This score was further validated in a testing set of 9466 adults. Deaths from baseline until 31 December 2015 were identified through record linkage to the National Death Index. During a median follow-up of 7·8 years among 40 074 participants, we documented 4904 deaths. Compared with participants in the lowest quintile of EDIP score, those in the highest quintile had a higher risk of overall death (hazard ratio (HR) = 1·19, 95 % CI 1·08, 1·32, Ptrend = 0·002), and deaths from cancer (HR = 1·41, 95 % CI 1·14, 1·74, Ptrend = 0·017) and CVD (HR = 1·22, 95 % CI 0·98, 1·53, Ptrend = 0·211). When stratified by age, the association of EDIP with overall mortality was stronger among individuals under 65 years of age (Pinteraction = 0·001). Diets with a higher inflammatory potential were associated with increased risk of overall and cancer-specific mortality. Interventions to reduce the adverse effect of pro-inflammatory diets may potentially promote health and longevity.

A compact wideband out-of-phase power divider (PD) with improved isolation performance is proposed. This divider is formed by connecting an additional stub for isolation to output ports of a traditional Marchand balun with a defected ground structure (DGS) been used. To verify the design, a prototype divider is fabricated and tested. The measured results validate the 53.86% band-width centered at 3.43 GHz with more than 15 dB return loss at all ports, more than 17 dB isolation, respectively.

A compact high-isolation power divider with bandpass response and high-frequency selectivity is presented in this letter. Two dual-mode resonators are used to realize filtering response. The circuit size of the proposed power divider can be reduced by using dual-mode capacitance loaded square meander loop resonators. Due to capacitive load, the resonator can exhibit slow-wave characteristics, which can be utilized to suppress harmonics and reduce size. The simulated and measured results show reasonable agreement.

The safety of maritime transportation has become increasingly important in recent decades. In this paper, a decision model (a multi-objective and multi-layer fuzzy optimisation model) for navigation risk in different sea areas is established. This is done according to the evaluation index system based on relative data extracted and analysed from Automatic Identification Systems (AIS) information and the multi-objective and multi-layer fuzzy optimisation theory. Then, sorted by an optimal relative membership degree vector and calculated from lower layer to higher layer, the sea areas which have higher navigation risk are selected. Finally, the decision model is shown to be scientific and practical since the results from it are basically consistent with real traffic in Chengshantou waters and the results from the fuzzy comprehensive evaluation model. With the decision model, navigation risk judgments in different sea areas can be offered. It can also provide decision making references to the design of ship routing systems, the layout of search and rescue sites, the configuration of rescue forces and the administration of navigation safety.

We report progress in growing non-polar a-plane III-nitride films and heterostructures over a-plane 4H-SiC. a-plane SiC is more closely lattice-matched to a-plane GaN than is r-plane sapphire. Consequently, better structural quality a-plane nitride films may result over a-plane SiC substrates. By migration enhanced metalorganic chemical vapor deposition (MEMOCVD), an atomically smooth (1120)AlN layer with RMS roughness of 0.3nm was obtained. From the results of XRD, the structural defects in the AlN layer on SiC substrates were strongly reduced compared to those grown on r-plane sapphire. Also by applying our selective area lateral epitaxy (SALE) growth procedure, we achieved high structural and optical quality a-plane GaN films on 4H-SiC with RMS roughness only 0.4nm. Therefore, non-polar III-nitride films and heterostructures on SiC substrates are promising building blocks for realizing high performance polarization-free devices.