Strategic investment Smit, Han T. J; Trigeorgis, Lenos
2004., 20120112, 2012, 2004, 2012-01-12
eBook
Corporate finance and corporate strategy have long been seen as different sides of the same coin. Though both focus on the same broad problem, investment decision-making, the gap between the two ...sides--and between theory and practice--remains embarrassingly large. This book synthesizes cutting-edge developments in corporate finance and related fields--in particular, real options and game theory--to help bridge this gap. In clear, straightforward exposition and through numerous examples and applications from various industries, Han Smit and Lenos Trigeorgis set forth an extended valuation framework for competitive strategies. The book follows a problem-solving approach that synthesizes ideas from game theory, real options, and strategy. Thinking in terms of options-games can help managers address questions such as: When is it best to invest early to preempt competitive entry, and when to wait? Should a firm compete in R&D or adopt an accommodating stance? How does one value growth options or infrastructure investments? The authors provide a wide range of valuation examples, such as acquisition strategies, R&D investment in high-tech sectors, joint research ventures, product introductions in consumer electronics, infrastructure, and oil exploration investment. Representing a major step beyond standard real options or strategy analysis, and extending the power of real options and strategic thinking in a rigorous fashion, Strategic Investment will be an indispensable guide and resource for corporate managers, MBA students, and academics alike.
Monitoring plastic concentrations in estuaries is vital in assessing the magnitude of terrestrial inputs to oceanic environments. Data on plastics ≤5mm in estuaries are scant. This study determined ...microplastic levels within five estuaries along the Durban coastline and on intervening beaches. Plastics were isolated from estuarine sediment, beach sediment and the surface water of each estuary and characterised. Sediment at the Bayhead area of Durban harbour had the highest average plastic concentrations (745.4±129.7 particles per 500ml) and an attenuating concentration trend away from the city centre was found. Prevailing south to north longshore drift was hypothesised to result in plastic accumulation on the northern shores of beaches with estuarine effluents, however, this was not found. Fragments composed the largest percent of plastics (59%) found in Bayhead, whereas fibres dominated other estuaries with proportions ranging from 38% of total plastics in the uMgeni estuary to 66% in the Mdloti.
•We categorized plastic pollution within estuaries along the Durban coastline.•The head of Durban Harbour had the highest average plastic concentrations.•High input and retention in harbours concentrates plastics.•We showed an attenuating plastic concentration trend away from the city centre.•Plastic fibres dominated at most estuaries.
Recent advances in highly multiplexed immunoassays have allowed systematic large-scale measurement of hundreds of plasma proteins in large cohort studies. In combination with genotyping, such studies ...offer the prospect to 1) identify mechanisms involved with regulation of protein expression in plasma, and 2) determine whether the plasma proteins are likely to be causally implicated in disease. We report here the results of genome-wide association (GWA) studies of 83 proteins considered relevant to cardiovascular disease (CVD), measured in 3,394 individuals with multiple CVD risk factors. We identified 79 genome-wide significant (p<5e-8) association signals, 55 of which replicated at P<0.0007 in separate validation studies (n = 2,639 individuals). Using automated text mining, manual curation, and network-based methods incorporating information on expression quantitative trait loci (eQTL), we propose plausible causal mechanisms for 25 trans-acting loci, including a potential post-translational regulation of stem cell factor by matrix metalloproteinase 9 and receptor-ligand pairs such as RANK-RANK ligand. Using public GWA study data, we further evaluate all 79 loci for their causal effect on coronary artery disease, and highlight several potentially causal associations. Overall, a majority of the plasma proteins studied showed evidence of regulation at the genetic level. Our results enable future studies of the causal architecture of human disease, which in turn should aid discovery of new drug targets.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In the last three decades the discovery of metabolites with biological activities from macroalgae has increased significantly. However, despite the intense research effort by academic and corporate ...institutions, very few products with real potential have been identified or developed. Based on Silverplatter MEDLINE and Aquatic Biology, Aquaculture & Fisheries Resources databases, the literature was searched for natural products from marine macroalgae in the Rhodophyta, Phaeophyta and Chlorophyta with biological and pharmacological activity. Substances that currently receive most attention from pharmaceutical companies for use in drug development, or from researchers in the field of medicine-related research include: sulphated polysaccharides as antiviral substances, halogenated furanones from Delisea pulchra as antifouling compounds, and kahalalide F from a species of Bryopsis as a possible treatment of lung cancer, tumours and AIDS. Other substances such as macroalgal lectins, fucoidans, kainoids and aplysiatoxins are routinely used in biomedical research and a multitude of other substances have known biological activities. The potential pharmaceutical, medicinal and research applications of these compounds are discussed.
Major depressive disorder (MDD) is a common complex disorder with a partly genetic etiology. We conducted a genome-wide association study of the MDD2000+ sample (2431 cases, 3673 screened controls ...and >1 M imputed single-nucleotide polymorphisms (SNPs)). No SNPs achieved genome-wide significance either in the MDD2000+ study, or in meta-analysis with two other studies totaling 5763 cases and 6901 controls. These results imply that common variants of intermediate or large effect do not have main effects in the genetic architecture of MDD. Suggestive but notable results were (a) gene-based tests suggesting roles for adenylate cyclase 3 (ADCY3, 2p23.3) and galanin (GAL, 11q13.3); published functional evidence relates both of these to MDD and serotonergic signaling; (b) support for the bipolar disorder risk variant SNP rs1006737 in CACNA1C (P=0.020, odds ratio=1.10); and (c) lack of support for rs2251219, a SNP identified in a meta-analysis of affective disorder studies (P=0.51). We estimate that sample sizes 1.8- to 2.4-fold greater are needed for association studies of MDD compared with those for schizophrenia to detect variants that explain the same proportion of total variance in liability. Larger study cohorts characterized for genetic and environmental risk factors accumulated prospectively are likely to be needed to dissect more fully the etiology of MDD.
Covering: up to 2022
Plants produce a wide range of structurally and biosynthetically diverse natural products to interact with their environment. These specialised metabolites typically evolve in ...limited taxonomic groups presumably in response to specific selective pressures. With the increasing availability of sequencing data, it has become apparent that in many cases the genes encoding biosynthetic enzymes for specialised metabolic pathways are not randomly distributed on the genome. Instead they are physically linked in structures such as arrays, pairs and clusters. The exact function of these clusters is debated. In this review we take a broad view of gene arrangement in plant specialised metabolism, examining types of structures and variation. We discuss the evolution of biosynthetic gene clusters in the wider context of metabolism, populations and epigenetics. Finally, we synthesise our observations to propose a new hypothesis for biosynthetic gene cluster formation in plants.
A significant subset of plant specialised metabolism genes are arranged in biosynthetic gene clusters. Here, we review these clusters and discuss their possible roles within the context of genome dynamics and metabolic evolution.
It has been hypothesized that hypovitaminosis D is associated with depression but epidemiological evidence is limited. We investigated the association between depressive disorders and related ...clinical characteristics with blood concentrations of 25-hydroxyvitamin D 25(OH)D in a large cohort. The sample consisted of participants (aged 18-65 years) from the Netherlands Study of Depression and Anxiety (NESDA) with a current (N=1102) or remitted (N=790) depressive disorder (major depressive disorder, dysthymia) defined according to DSM-IV criteria, and healthy controls (N=494). Serum levels of 25(OH)D measured and analyzed in multivariate analyses adjusting for sociodemographics, sunlight, urbanization, lifestyle and health. Of the sample, 33.6% had deficient or insufficient serum 25(OH)D (<50 nmol l(-1)). As compared with controls, lower 25(OH)D levels were found in participants with current depression (P=0.001, Cohen's d=0.21), particularly in those with the most severe symptoms (P=0.001, Cohen's d=0.44). In currently depressed persons, 25(OH)D was inversely associated with symptom severity (β=-0.19, s.e.=0.07, P=0.003) suggesting a dose-response gradient, and with risk (relative risk=0.90, 95% confidence interval=0.82-0.99, P=0.03) of having a depressive disorders at 2-year follow-up. This large cohort study indicates that low levels of 25(OH)D were associated to the presence and severity of depressive disorder suggesting that hypovitaminosis D may represent an underlying biological vulnerability for depression. Future studies should elucidate whether-the highly prevalent-hypovitaminosis D could be cost-effectively treated as part of preventive or treatment interventions for depression.
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths in the world. Metabolic reprogramming is considered a new hallmark of cancer, but it remains unclearly described ...in HCC. The dysregulation of the PI3K/AKT/mTOR signaling pathway is common in HCC and is, therefore, a topic of further research and the concern of developing a novel target for liver cancer therapy. In this review, we illustrate mechanisms by which this signaling network is accountable for regulating HCC cellular metabolism, including glucose metabolism, lipid metabolism, amino acid metabolism, pyrimidine metabolism, and oxidative metabolism, and summarize the ongoing clinical trials based on the inhibition of the PI3K/AKT/mTOR pathway in HCC.
Objective We conducted a prospective phase II clinical trial to determine the efficacy of sorafenib in patients with advanced radio-iodine refractory differentiated thyroid cancer. In this article, ...the long-term results are presented. Patients and methods Thirty-one patients with progressive metastatic or locally advanced radioactive iodine refractory differentiated thyroid cancer received sorafenib 400 mg orally twice daily. The study end points included response rate, progression-free survival (PFS), overall survival (OS), best response by Response Evaluation Criteria in Solid Tumors criteria 1.0, and toxicity. Results Median PFS was 18 months (95% confidence interval (95% CI): 7–29 months) and median OS was 34.5 months (95% CI: 19–50 months). Eight patients (31%) achieved a partial response and 11 patients (42%) showed stable disease after a median follow-up of 25 months (range 3.5–39 months). Toxicity mostly included hand foot syndrome, weight loss, diarrhea, and rash. Conclusion Sorafenib has clinically relevant antitumor activity in patients with progressive metastatic or locally advanced radio-iodine refractory differentiated thyroid cancer. Sorafenib can nowadays be considered as the standard option in these patients.
G protein‐coupled chemokine receptors and their peptidergic ligands are interesting therapeutic targets due to their involvement in various immune‐related diseases, including rheumatoid arthritis, ...multiple sclerosis, inflammatory bowel disease, chronic obstructive pulmonary disease, HIV‐1 infection and cancer. To tackle these diseases, a lot of effort has been focused on discovery and development of small‐molecule chemokine receptor antagonists. This has been rewarded by the market approval of two novel chemokine receptor inhibitors, AMD3100 (CXCR4) and Maraviroc (CCR5) for stem cell mobilization and treatment of HIV‐1 infection respectively. The recent GPCR crystal structures together with mutagenesis and pharmacological studies have aided in understanding how small‐molecule ligands interact with chemokine receptors. Many of these ligands display behaviour deviating from simple competition and do not interact with the chemokine binding site, providing evidence for an allosteric mode of action. This review aims to give an overview of the evidence supporting modulation of this intriguing receptor family by a range of ligands, including small molecules, peptides and antibodies. Moreover, the computer‐assisted modelling of chemokine receptor–ligand interactions is discussed in view of GPCR crystal structures. Finally, the implications of concepts such as functional selectivity and chemokine receptor dimerization are considered.
LINKED ARTICLES This article is part of a themed section on the Molecular Pharmacology of G Protein‐Coupled Receptors (GPCRs). To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue‐6. To view the 2010 themed section on the same topic visit http://onlinelibrary.wiley.com/doi/10.1111/bph.2010.159.issue‐5/issuetoc
PDF
