The bullseye snakehead (Channa marulius) is considered as an affordable and robust freshwater fish for farming in Asia. However, there is limited knowledge on the species' full nutritional ...requirements to date with extensive gaps in our knowledge and particularly in precision aspects of protein requirements. Therefore, a three-month feeding trial was conducted under semi-intensive farming conditions to determine the protein requirement of bullseye snakehead using test diets containing 40 (P40), 45 (P45), 50 (P50), and 55% (P55) crude protein levels. The growth performance results revealed that the 55% dietary protein group (P55) had the highest final mean weight (14.09 g fish-1), and net weight gain (12.82 g fish-1). When compared to other dietary treatments, the final weight (R2 = 0.921), and weight gain (R2 = 0.913), displayed a linear increasing trend as dietary protein is raised. The lowest FCR was observed in 50% (1.94±0.01) and 55% (1.97±0.01) CP diet groups compared to dietary treatments. Further analysis has shown that the body protein content also significantly increased as dietary protein was raised to 55%. Although, a reverse trend was found in body lipid levels with increasing protein in the diet. The incremental dietary protein also elevated proximal intestinal protease activity but decreased amylase and lipase activity. The overall essential and non-essential amino acids levels of snakehead fillet muscle reflected an increase in dietary protein. Overall, this study has shown that the fish fed a diet with 55% crude protein attained the highest growth performance and nutrient profile of the whole fish when compared to other dietary treatments tested. It would appear we did not obtain the maximum potential for growth under the present experimental conditions due to the upper protein constraint of 55% in the diet. Further quantitative studies are suggested.
This paper investigates an electricity time-of-use (TOU) tariff problem with the consideration of consumer behavior. Under the TOU tariff, we consider two periods: the peak and base periods. A ...two-level model is established to solve the TOU tariff problem: in the upper level, the producer determines the TOU tariff with the consideration of consumer behavior; in the lower level, the consumers respond to the TOU tariff through shifting some electricity consumption in the peak period to the base period. Using the traditional flat-rate (FR) tariff as a baseline, we verify the conditions under which the producer has incentives to adopt the TOU tariff. With the adoption of a general consumer transfer cost, we solve for the optimal TOU tariff under different situations. Our results demonstrate that proper adoption of the TOU tariff can create a win–win situation for both the producer and the consumers: the producer can increase its profit and the consumers can save their electricity cost. We further evaluate the effectiveness of the TOU tariff in terms of the peak demand reduction. Using a quadratic transfer cost, we obtain some managerial insights into the TOU tariff problem, and illustrate that the TOU tariff is always beneficial to the producer and the consumers under the quadratic transfer cost.
•This paper investigates a new electricity time-of-use (TOU) tariff problem with the consideration of consumer behavior.•We verify the conditions under which the producer has incentives to adopt the TOU tariff.•We solve for the optimal TOU tariff under different situations.•Our results show that proper adoption of the TOU tariff can create a win–win situation.•We obtain some managerial insights into the TOU tariff problem.
Activating mutations in one allele of an oncogene (heterozygous mutations) are widely believed to be sufficient for tumorigenesis. However, mutant allele specific imbalance (MASI) has been observed ...in tumors and cell lines harboring mutations of oncogenes.
We determined 1) mutational status, 2) copy number gains (CNGs) and 3) relative ratio between mutant and wild type alleles of KRAS, BRAF, PIK3CA and EGFR genes by direct sequencing and quantitative PCR assay in over 400 human tumors, cell lines, and xenografts of lung, colorectal, and pancreatic cancers. Examination of a public database indicated that homozygous mutations of five oncogenes were frequent (20%) in 833 cell lines of 12 tumor types. Our data indicated two major forms of MASI: 1) MASI with CNG, either complete or partial; and 2) MASI without CNG (uniparental disomy; UPD), due to complete loss of wild type allele. MASI was a frequent event in mutant EGFR (75%) and was due mainly to CNGs, while MASI, also frequent in mutant KRAS (58%), was mainly due to UPD. Mutant: wild type allelic ratios at the genomic level were precisely maintained after transcription. KRAS mutations or CNGs were significantly associated with increased ras GTPase activity, as measured by ELISA, and the two molecular changes were synergistic. Of 237 lung adenocarcinoma tumors, the small number with both KRAS mutation and CNG were associated with shortened survival.
MASI is frequently present in mutant EGFR and KRAS tumor cells, and is associated with increased mutant allele transcription and gene activity. The frequent finding of mutations, CNGs and MASI occurring together in tumor cells indicates that these three genetic alterations, acting together, may have a greater role in the development or maintenance of the malignant phenotype than any individual alteration.
Lung cancer cell lines have made a substantial contribution to lung cancer translational research and biomedical discovery. A systematic approach to initiating and characterizing cell lines from ...small cell and non–small cell lung carcinomas has led to the current collection of more than 200 lung cancer cell lines, a number that exceeds those for other common epithelial cancers combined. The ready availability and widespread dissemination of the lines to investigators worldwide have resulted in more than 9000 citations, including multiple examples of important biomedical discoveries. The high (but not perfect) genomic similarities between lung cancer cell lines and the lung tumor type from which they were derived provide evidence of the relevance of their use. However, major problems including misidentification or cell line contamination remain. Ongoing studies and new approaches are expected to reveal the full potential of the lung cancer cell line panel.
Macrophages, Inflammation, and Lung Cancer Conway, Emma M; Pikor, Larissa A; Kung, Sonia H Y ...
American journal of respiratory and critical care medicine,
2016-Jan-15, Letnik:
193, Številka:
2
Journal Article
Recenzirano
Lung cancer is the leading cause of cancer mortality worldwide, and at only 18%, it has one of the lowest 5-year survival rates of all malignancies. With its highly complex mutational landscape, ...treatment strategies against lung cancer have proved largely ineffective. However with the recent success of immunotherapy trials in lung cancer, there is renewed enthusiasm in targeting the immune component of tumors. Macrophages make up the majority of the immune infiltrate in tumors and are a key cell type linking inflammation and cancer. Although the mechanisms through which inflammation promotes cancer are not fully understood, two connected hypotheses have emerged: an intrinsic pathway, driven by genetic alterations that lead to neoplasia and inflammation, and an extrinsic pathway, driven by inflammatory conditions that increase cancer risk. Here, we discuss the contribution of macrophages to these pathways and subsequently their roles in established tumors. We highlight studies investigating the association of macrophages with lung cancer prognosis and discuss emerging therapeutic strategies for targeting macrophages in the tumor microenvironment.
Segmental copy-number variations (CNVs) in the human genome are associated with developmental disorders and susceptibility to diseases. More importantly, CNVs may represent a major genetic component ...of our phenotypic diversity. In this study, using a whole-genome array comparative genomic hybridization assay, we identified 3,654 autosomal segmental CNVs, 800 of which appeared at a frequency of at least 3%. Of these frequent CNVs, 77% are novel. In the 95 individuals analyzed, the two most diverse genomes differed by at least 9 Mb in size or varied by at least 266 loci in content. Approximately 68% of the 800 polymorphic regions overlap with genes, which may reflect human diversity in senses (smell, hearing, taste, and sight), rhesus phenotype, metabolism, and disease susceptibility. Intriguingly, 14 polymorphic regions harbor 21 of the known human microRNAs, raising the possibility of the contribution of microRNAs to phenotypic diversity in humans. This in-depth survey of CNVs across the human genome provides a valuable baseline for studies involving human genetics.
Human PIWI-interacting RNAs (piRNAs) are known to be expressed in germline cells, functionally silencing LINEs and SINEs. Their expression patterns in somatic tissues are largely uncharted. We ...analyzed 6,260 human piRNA transcriptomes derived from non-malignant and tumour tissues from 11 organs. We discovered that only 273 of the 20,831 known piRNAs are expressed in somatic non-malignant tissues. However, expression patterns of these piRNAs were able to distinguish tissue-of-origin. A total of 522 piRNAs are expressed in corresponding tumour tissues, largely distinguishing tumour from non-malignant tissues in a cancer-type specific manner. Most expressed piRNAs mapped to known transcripts, contrary to "piRNA clusters" reported in germline cells. We showed that piRNA expression can delineate clinical features, such as histological subgroups, disease stages, and survival. PiRNAs common to many cancer types might represent a core gene-set that facilitates cancer growth, while piRNAs unique to individual cancer types likely contribute to cancer-specific biology.
Resident microbial populations have been detected across solid tumors of diverse origins. Sequencing of the airway microbiota represents an opportunity for establishing a novel omics approach to ...early detection of lung cancer, as well as risk prediction of cancer development. We hypothesize that bacterial shifts in the pre-malignant lung may be detected in non-cancerous airway liquid biopsies collected during bronchoscopy. We analyzed the airway microbiome profile of near 400 patients: epithelial brushing samples from those with lung cancer, those who developed an incident cancer, and those who do not develop cancer after 10-year follow-up. Using linear discriminate analysis, we define and validate a microbial-based classifier that is able to predict incident cancer in patients before diagnosis with no clinical signs of cancer. Our results demonstrate the potential of using lung microbiome profiling as a method for early detection of lung cancer.
We propose a deep neural network framework for computing prices and deltas of American options in high dimensions. The architecture of the framework is a sequence of neural networks, where each ...network learns the difference of the price functions between adjacent timesteps. We introduce the least squares residual of the associated backward stochastic differential equation as the loss function. Our proposed framework yields prices and deltas for the entire spacetime, not only at a given point (e.g. t = 0). The computational cost of the proposed approach is quadratic in dimension, which addresses the curse of dimensionality issue that state-of-the-art approaches suffer. Our numerical simulations demonstrate these contributions, and show that the proposed neural network framework outperforms state-of-the-art approaches in high dimensions.
Summary
To identify the role of vitamin K2 for the prevention and treatment of osteoporosis in postmenopausal women, we conducted this meta-analysis of 19 randomized controlled trials. Our results ...showed that vitamin K2 might play a role in maintaining the bone mineral density and in reducing the incidence of fractures for postmenopausal women with osteoporosis.
Introduction
Vitamin K2 has been revealed to be effective in the prevention and treatment of osteoporosis in Japan, which was not confirmed in western countries. Thus, we conduct this meta-analysis to verify the hypothesis that vitamin K2 plays a role in the prevention and treatment of osteoporosis for postmenopausal women.
Methods
We searched the Cochrane Library, Pub Med, EMBASE, and ISI web of knowledge (until December 1, 2013) and reference lists of eligible articles. A meta-analysis of all-including randomized controlled trials was then performed.
Results
Nineteen randomized controlled trials encompassing 6759 participants have met the inclusion criteria. Subgroup analysis of postmenopausal women with osteoporosis revealed a significant improvement of vertebral BMD for both medium-term and long-term results favoring vitamin K2 group (
p
< 0.00001 and
p
= 0.0005). However, no significant difference in BMD changes was revealed for the non-osteoporosis subgroup analysis. As for the incidence of fractures, pooled analysis of the seven related studies demonstrated no significant difference in the incidence of fractures favoring vitamin K2 (RR = 0.63,
p
= 0.08). However, sensitivity analysis by rejecting the study inducing heterogeneity demonstrated a significant difference in the incidence of fractures favoring vitamin K2 (RR = 0.50,
p
= 0.0005). Significant differences were found in undercarboxylated osteocalcin reduction and osteocalcin increment. The result of adverse reaction analysis showed that vitamin K2 group seemed to have a higher adverse reaction rate (RR = 1.22,
p
= 0.06).
Conclusions
This meta-analysis seemed to support the hypothesis that vitamin K2 plays kind of a role in the maintenance and improvement of vertebral BMD and the prevention of fractures in postmenopausal women with osteoporosis. The reduction of undercarboxylated osteocalcin and increment of osteocalcin may have some relation to the process of bone mineralization. However, the effect of vitamin K2 for postmenopausal women without osteoporosis had not been identified. Further high-quality RCTs with large sample size are needed to confirm the role of vitamin K2 in osteoporosis for postmenopausal women.
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