Identification of the genetic bases for bipolar disorder remains a challenge for the understanding of this disease. Association between 76 candidate genes and bipolar disorder was tested by ...genotyping 90 single-nucleotide polymorphisms (SNPs) in these genes in 136 parent-proband trios. In this preliminary analysis, SNPs in two genes, brain-derived neurotrophic factor (BDNF) and the alpha subunit of the voltage-dependent calcium channel were associated with bipolar disorder at the P<0.05 level. In view of the large number of hypotheses tested, the two nominally positive associations were then tested in independent populations of bipolar patients and only BDNF remains a potential risk gene. In the replication samples, excess transmission of the valine allele of amino acid 66 of BDNF was observed in the direction of the original result in an additional sample of 334 parent-proband trios (T/U=108/87, P=0.066). Resequencing of 29 kb surrounding the BDNF gene identified 44 additional SNPs. Genotyping eight common SNPs identified three additional markers transmitted to bipolar probands at the P < 0.05 level. Strong LD was observed across this region and all adjacent pairwise haplotypes showed excess transmission to the bipolar proband. Analysis of these haplotypes using TRANSMIT revealed a global P value of 0.03. A single haplotype was identified that is shared by both the original dataset and the replication sample that is uniquely marked by both the rare A allele of the original SNP and a novel allele 11.5 kb 3'. Therefore, this study of 76 candidate genes has identified BDNF as a potential risk allele that will require additional study to confirm.
The combination of anaerobic digestion and transesterification technologies to treat food waste avoids the environmental problems associated with other treatment methods and effectively utilizes food ...waste to produce valuable products for society. However, as the anaerobic mono-digestion of food waste is not as efficient as anaerobic co-digestion of food waste with other substrates, this needs to be considered in food waste treatment system planning. Few studies on the mixed treatment of food waste with other substrates have considered the system from the economic, environmental, and social perspectives. Therefore, this paper comprehensively considered the economic, environmental, and social objectives of food waste treatment systems and developed a multi-objective optimization model to investigate the optimal systems operational strategy for food waste mixed treatment with other substrates by anaerobic co-digestion and transesterification. Uncertainties regarding the source quantities of food waste and substrates are solved in the proposed model using trapezoidal fuzzy numbers, and a case study in China is given to assess the validity and practicality of the proposed model. It was found that different substrate types and different mixing proportions affected the optimal system decisions, environmental and economic objectives were mutually constraining, and there was a positive relationship between the social objectives and the economic and environmental objectives.
We have demonstrated that tracheal insufflation of recombinant plasmid DNA results in transfection of rat lungs to the same extent as insufflation of plasmid-cationic liposome complex. To understand ...this observation better, we investigated the in vitro gene transfer of plasmid DNA in the presence and absence of cationic liposome and the effect of surfactant on gene transfer. The chloramphenicol acetyltransferase (CAT) expression plasmids pBL-CAT and pSV-CAT were studied in three cell types: rat fetal lung fibroblast (RFL-6), calf pulmonary artery endothelial cell (CPAE), and rat type II alveolar epithelial cell (type II AE). Three cationic liposomes were tested: DDAB (dimethyl-dioctadecyl ammonium bromide)-liposome, DOTAP (dioleoyltrimethyl ammonium propane)-liposome, and lipofectin. The results revealed that (i) plasmid DNA alone caused a dose-dependent, low-level transfection, most efficiently in RFL-6 followed by CPAE and type II AE, (ii) DDAB-liposome markedly enhanced gene transfer, most efficiently in RFL-6 followed by CPAE and type II AE, (iii) Survanta, a naturally derived surfactant preparation, and Exosurf, a synthetic surfactant, while having no effect on in vitro gene transfer by plasmid DNA alone, markedly inhibited cationic liposome-mediated gene transfer, (iv) dipalmitoyl phosphatidylcholine was responsible for the inhibitory effect of Exosurf, and (v) inhibition of cationic liposome-mediated gene transfer by Exosurf was not due to inhibition of plasmid DNA-cationic liposome complex uptake or interference with the promoter and enhancer. The observed inhibition of cationic liposome-mediated gene transfer by surfactant may in part explain our previous observation that tracheal insufflation of plasmid DNA and plasmid-cationic liposome complex results in equal lung gene transfer.
In mouse melanocytes, myosin Va is recruited onto the surface of melanosomes by a receptor complex containing Rab27a that is present in the melanosome membrane and melanophilin (Mlp), which links ...myosin Va to Rab27a. In this study, we show that Mlp is also a microtubule plus end-tracking protein or +TIP. Moreover, myosin Va tracks the plus end in a Mlp-dependent manner. Data showing that overexpression and short inhibitory RNA knockdown of the +TIP EB1 have opposite effects on Mlp-microtubule interaction, that Mlp interacts directly with EB1, and that deletion from Mlp of a region similar to one in the adenomatous polyposis coli protein involved in EB1 binding blocks Mlp's ability to plus end track argue that Mlp tracks the plus end directly by hitchhiking on EB1. These results identify a novel +TIP and indicate that vertebrate cells possess a +TIP complex that is similar to the Myo2p-Kar9p-Bim1p complex in yeast. We suggest that the +TIP complex identified in this study may serve to focus the transfer of melanosomes from microtubules to actin at the microtubule plus end.
We present a robust model for determining the optimal order quantity and market selection for short-life-cycle products in a single period, newsvendor setting. Due to limited information about demand ...distribution in particular for short-life-cycle products, stochastic modeling approaches may not be suitable. We propose the minimax regret multi-market newsvendor model, where the demands are only known to be bounded within some given interval. In the basic version of the problem, a linear time solution method is developed. For the capacitated case, we establish some structural results to reduce the problem size, and then propose an approximation solution algorithm based on integer programming. Finally, we compare the performance of the proposed minimax regret model against the typical average-case and worst-case models. Our test results demonstrate that the proposed minimax regret model outperformed the average-case and worst-case models in terms of risk-related criteria and mean profit, respectively.
In this work, the problem of allocating a set of production lots to satisfy customer orders is considered. This research is of relevance to lot-to-order matching problems in semiconductor supply ...chain settings. We consider that lot-splitting is not allowed during the allocation process due to standard practices. Furthermore, lot-sizes are regarded as uncertain planning data when making the allocation decisions due to potential yield loss. In order to minimize the total penalties of demand un-fulfillment and over-fulfillment, a robust mixed-integer optimization approach is adopted to model is proposed the problem of allocating a set of work-in-process lots to customer orders, where lot-sizes are modeled using ellipsoidal uncertainty sets. To solve the optimization problem efficiently we apply the techniques of branch-and-price and Benders decomposition. The advantages of our model are that it can represent uncertainty in a straightforward manner with little distributional assumptions, and it can produce solutions that effectively hedge against the uncertainty in the lot-sizes using very reasonable amounts of computational effort.
: Two new HLA‐DRB1 alleles have been found by using high‐resolution sequence‐based typing. The two sequences have been officially named DRB1*1350 (HWS10001327‐AY048687) and DRB1*140502 ...(HWS10001790‐AY129430). DRB1*1350 differs from DRB1*110101 by two amino acids at positions 37 (Y→N) and 58 (A→E). This allele may arise from gene conversion between DRB1*110101 and DRB1*130201 or DRB1*030101, which are commonly found in Taiwan populations. The other allele, DRB1*140502, obtained from a patient with rheumatoid arthritis, differs from DRB1*140501 at codon 58 (GCC→GCT). However, it causes no change in amino acid sequence and would therefore not have direct clinical implications.
Identification of the genetic bases for bipolar disorder remains a challenge for the understanding of this disease. Association between 76 candidate genes and bipolar disorder was tested by ...genotyping 90 single-nucleotide polymorphisms (SNPs) in these genes in 136 parent-proband trios. In this preliminary analysis, SNPs in two genes, brain-derived neurotrophic factor (BDNF) and the alpha subunit of the voltage-dependent calcium channel were associated with bipolar disorder at the P<0.05 level. In view of the large number of hypotheses tested, the two nominally positive associations were then tested in independent populations of bipolar patients and only BDNF remains a potential risk gene. In the replication samples, excess transmission of the valine allele of amino acid 66 of BDNF was observed in the direction of the original result in an additional sample of 334 parent-proband trios (T/U=108/87, P=0.066). Resequencing of 29 kb surrounding the BDNF gene identified 44 additional SNPs. Genotyping eight common SNPs identified three additional markers transmitted to bipolar probands at the P < 0.05 level. Strong LD was observed across this region and all adjacent pairwise haplotypes showed excess transmission to the bipolar proband. Analysis of these haplotypes using TRANSMIT revealed a global P value of 0.03. A single haplotype was identified that is shared by both the original dataset and the replication sample that is uniquely marked by both the rare A allele of the original SNP and a novel allele 11.5 kb 3'. Therefore, this study of 76 candidate genes has identified BDNF as a potential risk allele that will require additional study to confirm.
...of the posts' deletion, the court ruled that the jury would be instructed that it could infer that the content of the Trustee's post evidenced a discriminatory animus towards the plaintiffs, in ...which case the Village would be precluded from offering evidence to rebut the inference.
Hypoxia plays a critical role in tumor progression including invasion and metastasis. To determine critical genes regulated by hypoxia that promote invasion and metastasis, we screen fifty hypoxia ...inducible genes for their effects on invasion. In this study, we identify v-maf musculoaponeurotic fibrosarcoma oncogene homolog F (MAFF) as a potent regulator of tumor invasion without affecting cell viability. MAFF expression is elevated in metastatic breast cancer patients and is specifically correlated with hypoxic tumors. Combined ChIP- and RNA-sequencing identifies IL11 as a direct transcriptional target of the heterodimer between MAFF and BACH1, which leads to activation of STAT3 signaling. Inhibition of IL11 results in similar levels of metastatic suppression as inhibition of MAFF. This study demonstrates the oncogenic role of MAFF as an activator of the IL11/STAT3 pathways in breast cancer.
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