Implications of gain functions in fisheries management

The appealing concept of optimal harvesting is often used in fisheries to obtain new management strategies. However, optimality depends on the objective function, which often varies, reflecting the interests of different groups of people. The aim of maximum sustainable yield is to extract the greatest amount of food from replenishable resources in a sustainable way. Maximum sustainable yield may not be desirable from an economic point of view. Maximum economic yield that maximizes the profit of fishing fleets (harvesting sector) but ignores socio-economic benefits such as employment and other positive externalities. It may be more appropriate to use the maximum economic yield that which is based on the value chain of the overall fishing sector, to reflect better society's interests. How to make more efficient use of a fishery for society rather than fishing operators depends critically on the gain function parameters including multiplier effects and inclusion or exclusion of certain costs. In particular, the optimal effort level based on the overall value chain moves closer to the optimal effort for the maximum sustainable yield because of the multiplier effect. These issues are illustrated using the Australian Northern Prawn Fishery.

A Bayesian decision approach for sample size determination in phase II trials

Stallard (1998, Biometrics 54, 279-294) recently used Bayesian decision theory for sample-size determination in phase II trials. His design maximizes the expected financial gains in the development of a new treatment. However, it results in a very high probability (0.65) of recommending an ineffective treatment for phase III testing. On the other hand, the expected gain using his design is more than 10 times that of a design that tightly controls the false positive error (Thall and Simon, 1994, Biometrics 50, 337-349). Stallard's design maximizes the expected gain per phase II trial, but it does not maximize the rate of gain or total gain for a fixed length of time because the rate of gain depends on the proportion: of treatments forwarding to the phase III study. We suggest maximizing the rate of gain, and the resulting optimal one-stage design becomes twice as efficient as Stallard's one-stage design. Furthermore, the new design has a probability of only 0.12 of passing an ineffective treatment to phase III study.

L2-Stability Of A Class Of Nonlinear-Systems

Sufficient conditions are given for the L2-stability of a class of feedback systems consisting of a linear operator G and a nonlinear gain function, either odd monotone or restricted by a power-law, in cascade, in a negative feedback loop. The criterion takes the form of a frequency-domain inequality, Re[1 + Z(jω)] G(jω) δ > 0 ω ε (−∞, +∞), where Z(jω) is given by, Z(jω) = β[Y1(jω) + Y2(jω)] + (1 − β)[Y3(jω) − Y3(−jω)], with 0 β 1 and the functions y1(·), y2(·) and y3(·) satisfying the time-domain inequalities, ∝−∞+∞¦y1(t) + y2(t)¦ dt 1 − ε, y1(·) = 0, t < 0, y2(·) = 0, t > 0 and ε > 0, and , c2 being a constant depending on the order of the power-law restricting the nonlinear function. The criterion is derived using Zames' passive operator theory and is shown to be more general than the existing criteria

One-dimensional improvement and two-dimensional and 3-dimensional treatments for stable oscillation condition, mode structure and power output in high-speed-flow lasers

For high-speed-flow lasers, the one-dimensional and first-order approximate treatment in[1] under approximation of geometrical optics is improved still within the scope of approx-imation of geometrical optics. The strict accurate results are obtained, and what is more,two- and three-dimensional treatments are done. Thus for two- and three-dimensional cases, thestable oscillation condition, the formulae of power output and analytical expression of modesunder approximation of geometrical optics (in terms of gain function) are derived. Accord-ing to the present theory, one-and two-dimensional calculations for the typical case of Gerry'sexperiment are presented. All the results coincide well with the experiment and are better thanthe results obtained in [1].In addition, the applicable scope of Lee's stable oscillation condition given by [1] is ex-panded; the condition for the approximation of gcometrical optics to be applied to mode con-structure in optical cavity is obtained for the first time and the difference between thiscondition and that for free space is also pointed out in the present work.

Decision-theoretic designs for phase II clinical trials allowing for competing studies

This article describes an approach to optimal design of phase II clinical trials using Bayesian decision theory. The method proposed extends that suggested by Stallard (1998, Biometrics54, 279–294) in which designs were obtained to maximize a gain function including the cost of drug development and the benefit from a successful therapy. Here, the approach is extended by the consideration of other potential therapies, the development of which is competing for the same limited resources. The resulting optimal designs are shown to have frequentist properties much more similar to those traditionally used in phase II trials.

Bayesian decision procedures for binary and continuous bivariate dose-escalation studies

In this paper, Bayesian decision procedures are developed for dose-escalation studies based on binary measures of undesirable events and continuous measures of therapeutic benefit. The methods generalize earlier approaches where undesirable events and therapeutic benefit are both binary. A logistic regression model is used to model the binary responses, while a linear regression model is used to model the continuous responses. Prior distributions for the unknown model parameters are suggested. A gain function is discussed and an optional safety constraint is included. Copyright (C) 2006 John Wiley & Sons, Ltd.

Measurement of gain spectrum for semiconductor lasers utilizing integrations of product of emission spectrum and a phase function over one mode interval

A technique based on the integrations of the product of amplified spontaneous emission spectrum and a phase function over one mode interval is proposed for measuring gain spectrum for Fabry-Perot semiconductor lasers, and a gain correction factor related to the response function of the optical spectrum analyzer (OSA) is obtained for improving the accuracy of measured gain spectrum. The gain spectra with a difference less than 1.3 cm(-1) from 1500 to 1600 nm are obtained for a 250-mum-long semiconductor laser at the OSA resolution of 0.06, 0.1, 0.2, and 0.5 nm. The corresponding gain correction factor is about 9 cm(-1) at the resolution of 0.5 nm. The gain spectrum measured at the resolution of 0.5 nm has the same accuracy as that obtained by the Hakki-Paoli method at the resolution of 0.06 nm for the laser with the mode interval of 1.3 nm.

A gain-of-function mutation in the HIF2A gene in familial erythrocytosis

Hypoxia-inducible factor (HIF) a, which has three isoforms, is central to the continuous balancing of the supply and demand of oxygen throughout the body. HIF-a is a transcription factor that modulates a wide range of processes, including erythropoiesis, angiogenesis, and cellular metabolism. We describe a family with erythrocytosis and a mutation in the HIF2A gene, which encodes the HIF-2a protein. Our functional studies indicate that this mutation leads to stabilization of the HIF-2a protein and suggest that wild-type HIF-2a regulates erythropoietin production in adults.

Cardiopulmonary function in two human disorders of the hypoxia-inducible factor (HIF) pathway: von Hippel-Lindau disease and HIF-2 alpha gain-of-function mutation

The hypoxia-inducible factors (HIFs; isoforms HIF-1 alpha, HIF-2 alpha, HIF-3 alpha) mediate many responses to hypoxia. Their regulation is principally by oxygen-dependent degradation, which is initiated by hydroxylation of specific proline residues followed by binding of von Hippel-Lindau (VHL) protein. Chuvash polycythemia is a disorder with elevated HIF. It arises through germline homozygosity for hypomorphic VHL alleles and has a phenotype of hematological, cardiopulmonary, and metabolic abnormalities. This study explores the phenotype of two other HIF pathway diseases: classic VHL disease and HIF-2 alpha gain-of-function mutation. No cardiopulmonary abnormalities were detected in classic VHL disease. HIF-2 alpha gain-of-function mutations were associated with pulmonary hypertension, increased cardiac output, increased heart rate, and increased pulmonary ventilation relative to metabolism. Comparison of the HIF-2 alpha gain-of-function responses with data from studies of Chuvash polycythemia suggested that other aspects of the Chuvash phenotype were diminished or absent. In classic VHL disease, patients are germline heterozygous for mutations in VHL, and the present results suggest that a single wild-type allele for VHL is sufficient to maintain normal cardiopulmonary function. The HIF-2 alpha gain-of-function phenotype may be more limited than the Chuvash phenotype either because HIF-1 alpha is not elevated in the former condition, or because other HIF-independent functions of VHL are perturbed in Chuvash polycythemia.-Formenti, F., Beer, P. A., Croft, Q. P. P., Dorrington, K. L., Gale, D. P., Lappin, T. R. J., Lucas, G. S., Maher, E. R., Maxwell, P. H., McMullin, M. F., O'Connor, D. F., Percy, M. J., Pugh, C. W., Ratcliffe, P. J., Smith, T. G., Talbot, N. P., Robbins, P. A. Cardiopulmonary function in two human disorders of the hypoxia-inducible factor (HIF) pathway: von Hippel-Lindau disease and HIF-2 alpha gain-of-function mutation. FASEB J. 25, 2001-2011 (2011). www.fasebj.org

FGFR2 Mutation Confers a Less Drastic Gain of Function in Mesenchymal Stem Cells Than in Fibroblasts

Gain-of-function mutations in FGFR2 cause Apert syndrome (AS), a disease characterized by craniosynostosis and limb bone defects both due to abnormalities in bone differentiation and remodeling. Although the periosteum is an important cell source for bone remodeling, its role in craniosynostosis remains poorly characterized. We hypothesized that periosteal mesenchymal stem cells (MSCs) and fibroblasts from AS patients have abnormal cell phenotypes that contribute to the recurrent fusion of the coronal sutures. MSCs and fibroblasts were obtained from the periostea of 3 AS patients (S252W) and 3 control individuals (WT). We evaluated the proliferation, migration, and osteogenic differentiation of these cells. Interestingly, S252W mutation had opposite effects on different cell types: S252W MSCs proliferated less than WT MSCs, while S252W fibroblasts proliferated more than WT fibroblasts. Under restrictive media conditions, only S252W fibroblasts showed enhanced migration. The presence of S252W mutation increased in vitro and in vivo osteogenic differentiation in both studied cell types, though the difference compared to WT cells was more pronounced in S252W fibroblasts. This osteogenic differentiation was reversed through inhibition of JNK. We demonstrated that S252W fibroblasts can induce osteogenic differentiation in periosteal MSCs but not in MSCs from another tissue. MSCs and fibroblasts responded differently to the pathogenic effects of the FGFR2(S252W) mutation. We propose that cells from the periosteum have a more important role in the premature fusion of cranial sutures than previously thought and that molecules in JNK pathway are strong candidates for the treatment of AS patients.

Gain-of-function haplotype in the epithelial calcium channel TRPV6 is a risk factor for renal calcium stone formation

The rate-limiting step of dietary calcium absorption in the intestine requires the brush border calcium entry channel TRPV6. The TRPV6 gene was completely sequenced in 170 renal calcium stone patients. The frequency of an ancestral TRPV6 haplotype consisting of three non-synonymous polymorphisms (C157R, M378V, M681T) was significantly higher (P = 0.039) in calcium stone formers (8.4%; derived = 502, ancestral = 46) compared to non-stone-forming individuals (5.4%; derived = 645, ancestral = 37). Mineral metabolism was investigated on four different calcium regimens: (i) free-choice diet, (ii) low calcium diet, (iii) fasting and (iv) after a 1 g oral calcium load. When patients homozygous for the derived haplotype were compared with heterozygous patients, no differences were found with respect to the plasma concentrations of 1,25-vitamin D, PTH and calcium, and the urinary excretion of calcium. In one stone-forming patient, the ancestral haplotype was found to be homozygous. This patient had absorptive hypercalciuria. We therefore expressed the ancestral protein (157R+378V+681T) in Xenopus oocytes and found a significantly enhanced calcium permeability when tested by a (45)Ca(2+) uptake assay (7.11 +/- 1.93 versus 3.61 +/- 1.01 pmol/min/oocyte for ancestral versus derived haplotype, P < 0.01). These results suggest that the ancestral gain-of-function haplotype in TRPV6 plays a role in calcium stone formation in certain forms of absorptive hypercalciuria.