457 research outputs found
Towards the design of a blending system for precoloured fibres
In order to create a commercial system for blending precoloured fibres that will appear visually solid once combined, it is necessary to understand the maximum colour difference required between the blend components. Based on this understanding, the lowest number of primaries required to populate a given colour gamut can be determined. A series of psychophysical experiments was carried out to explore the colour difference between fibre-blend components and whether the resulting blended samples are perceived as visually solid. Experiments were carried out with loose stock fibre, yarn and knitted samples. Generally, it was found that the likelihood a blend appeared as visually solid increased as the average colour difference between the blend components, or primaries, decreased. The value of the mean colour difference at which 50% of participants viewed the blend as being visually solid was found to be 20.8, 20.5 and 18.0 for fibre, yarn and knitted samples, respectively. Consequently, it was found that it was more difficult to obtain a solid shade with the knitted form than with the loose stock fibre form
In vivo activity of the dual SYK/FLT3 inhibitor TAK-659 against pediatric acute lymphoblastic leukemia xenografts
Background: While children with acute lymphoblastic leukemia (ALL) experience close to a 90% likelihood of cure, the outcome for certain high-risk pediatric ALL subtypes remains dismal. Spleen tyrosine kinase (SYK) is a prominent cytosolic nonreceptor tyrosine kinase in pediatric B-lineage ALL (B-ALL). Activating mutations or overexpression of Fms-related receptor tyrosine kinase 3 (FLT3) are associated with poor outcome in hematological malignancies. TAK-659 (mivavotinib) is a dual SYK/FLT3 reversible inhibitor, which has been clinically evaluated in several other hematological malignancies. Here, we investigate the in vivo efficacy of TAK-659 against pediatric ALL patient-derived xenografts (PDXs). Methods: SYK and FLT3 mRNA expression was quantified by RNA-seq. PDX engraftment and drug responses in NSG mice were evaluated by enumerating the proportion of human CD45+ cells (%huCD45+) in the peripheral blood. TAK-659 was administered per oral at 60 mg/kg daily for 21 days. Events were defined as %huCD45+ ≥ 25%. In addition, mice were humanely killed to assess leukemia infiltration in the spleen and bone marrow (BM). Drug efficacy was assessed by event-free survival and stringent objective response measures. Results: FLT3 and SYK mRNA expression was significantly higher in B-lineage compared with T-lineage PDXs. TAK-659 was well tolerated and significantly prolonged the time to event in six out of eight PDXs tested. However, only one PDX achieved an objective response. The minimum mean %huCD45+ was significantly reduced in five out of eight PDXs in TAK-659-treated mice compared with vehicle controls. Conclusions: TAK-659 exhibited low to moderate single-agent in vivo activity against pediatric ALL PDXs representative of diverse subtypes
Medical Image Retrieval: Past and Present
With the widespread dissemination of picture archiving and communication systems (PACSs) in hospitals, the amount of imaging data is rapidly increasing. Effective image retrieval systems are required to manage these complex and large image databases. The authors reviewed the past development and the present state of medical image retrieval systems including text-based and content-based systems. In order to provide a more effective image retrieval service, the intelligent content-based retrieval systems combined with semantic systems are required
Don't Fall Off the Adaptation Cliff: When Asymmetrical Fitness Selects for Suboptimal Traits
The cliff-edge hypothesis introduces the counterintuitive idea that the trait value associated with the maximum of an asymmetrical fitness function is not necessarily the value that is selected for if the trait shows variability in its phenotypic expression. We develop a model of population dynamics to show that, in such a system, the evolutionary stable strategy depends on both the shape of the fitness function around its maximum and the amount of phenotypic variance. The model provides quantitative predictions of the expected trait value distribution and provides an alternative quantity that should be maximized (“genotype fitness”) instead of the classical fitness function (“phenotype fitness”). We test the model's predictions on three examples: (1) litter size in guinea pigs, (2) sexual selection in damselflies, and (3) the geometry of the human lung. In all three cases, the model's predictions give a closer match to empirical data than traditional optimization theory models. Our model can be extended to most ecological situations, and the evolutionary conditions for its application are expected to be common in nature
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Equal fitness paradigm explained by a trade-off between generation time and energy production rate
Most plant, animal and microbial species of widely varying body size and lifestyle are nearly equally fit as evidenced by their coexistence and persistence through millions of years. All organisms compete for a limited supply of organic chemical energy, derived mostly from photosynthesis, to invest in the two components of fitness: survival and production. All organisms are mortal because molecular and cellular damage accumulates over the lifetime; life persists only because parents produce offspring. We call this the equal fitness paradigm. The equal fitness paradigm occurs because: (1) there is a trade-off between generation time and productive power, which have equal-but-opposite scalings with body size and temperature; smaller and warmer organisms have shorter lifespans but produce biomass at higher rates than larger and colder organisms; (2) the energy content of biomass is essentially constant, ~22.4 kJ g−1 dry body weight; and (3) the fraction of biomass production incorporated into surviving offspring is also roughly constant, ~10–50%. As organisms transmit approximately the same quantity of energy per gram to offspring in the next generation, no species has an inherent lasting advantage in the struggle for existence. The equal fitness paradigm emphasizes the central importance of energy, biological scaling relations and power–time trade-offs in life history, ecology and evolution
Mutation Accumulation May Be a Minor Force in Shaping Life History Traits
Is senescence the adaptive result of tradeoffs between younger and older ages or the nonadaptive burden of deleterious mutations that act at older ages? To shed new light on this unresolved question we combine adaptive and nonadaptive processes in a single model. Our model uses Penna's bit-strings to capture different age-specific mutational patterns. Each pattern represents a genotype and for each genotype we find the life history strategy that maximizes fitness. Genotypes compete with each other and are subject to selection and to new mutations over generations until equilibrium in gene-frequencies is reached. The mutation-selection equilibrium provides information about mutational load and the differential effects of mutations on a life history trait - the optimal age at maturity. We find that mutations accumulate only at ages with negligible impact on fitness and that mutation accumulation has very little effect on the optimal age at maturity. These results suggest that life histories are largely determined by adaptive processes. The non-adaptive process of mutation accumulation seems to be unimportant at evolutionarily relevant ages
Advance care planning for cancer patients: A systematic review of perceptions and experiences of patients, families and healthcare providers
Background Patients with advanced cancer may benefit from end of life (EOL) planning, but there is evidence that their willingness and desire to engage in advance care planning (ACP) varies. The reasons for this remain poorly understood. Previous reviews on ACP most commonly report outcome measures related to medical interventions and type of care. Synthesis of the literature, which aims to illuminate the salient characteristics of ACP and investigates the psychological and social features of preparation for the EOL, is required. Methods We searched Medline, EMBASE, PsychINFO, CINAHL, and the Cochrane Central Register of Controlled Trials for studies on perceptions or experiences regarding ACP of adults with cancer, family, friends, or professionals caring for this group. Databases were searched from earliest records to 19 November 2014. A thematic analysis of the literature generated conceptual themes. Results Of the 2483 studies identified, 40 were eligible for inclusion. Studies addressed the relational nature of ACP, fear surrounding ACP, the conceptual complexity of autonomy, and the influence of institutional culture and previous healthcare experiences on ACP. Conclusions The complex social and emotional environments within which EOL planning is initiated and actioned are not sufficiently embedded within standardized ACP. The notion that ACP is concerned principally with the ‘right’ to self-determination through control over treatment choices at the EOL may misrepresent the way that ACP actually occurs in cancer care and ultimately conflict with the deeper concerns and needs of patients, who experience ACP as relational, emotional, and social
Dipolar interactions and anisotropic magnetoresistance in metallic granular systems
We revisit the theory of magnetoresistance for a system of nanoscopic
magnetic granules in metallic matrix. Using a simple model for the spin
dependent perturbation potential of the granules, we solve Boltzmann equation
for the spin dependent components of the non equilibrium electronic
distribution function. For typical values of the geometric parameters in
granular systems, we find a peculiar structure of the distribution function of
conduction electrons, which is at variance with the two-current model of
conduction in inhomogeneous systems. Our treatment explicitly includes the
effects of dipolar correlations yielding a magnetoresistance ratio which
contains, in addition to the term proportional to the square of uniform
magnetization (), a weak anisotropic contribution
depending on the angle between electric and magnetic fields, and arising from
the anisotropic character of dipolar interactions.Comment: 9 pages, 2 figures, accepted in PR
GnRH and LHR gene variants predict adverse outcome in premenopausal breast cancer patients
Background: Breast cancer development and progression are dependent on estrogen activity. In premenopausal women, estrogen production is mainly regulated through the hypothalamic-pituitary-gonadal (HPG) axis. Methods: We have investigated the prognostic significance of two variants of genes involved in the HPG-axis, the GnRH (encoding gonadotropin-releasing hormone) 16Trp/Ser genotype and the LHR (encoding the luteinizing hormone receptor) insLQ variant, in retrospectively collected premenopausal breast cancer patients with a long follow-up (median follow-up of 11 years for living patients). Results: Carriership was not related with breast cancer risk (the case control study encompassed 278 premenopausal cases and 1,758 premenopausal controls). A significant adverse relationship of the LHR insLQ and GnRH 16Ser genotype with disease free survival (DFS) was observed in premenopausal (hormone receptor positive) breast cancer patients. In particular, those patients carrying both the GnRH 16Ser and LHR insLQ allele (approximately 25%) showed a significant increased risk of relapse, which was independent of traditional prognostic factors (hazard ratio 2.14; 95% confidence interval 1.32 to 3.45; P = 0.002). Conclusion: We conclude that the LHR insLQ and GnRH 16Ser alleles are independently associated with shorter DFS in premenopausal patients. When validated, these findings may provide a lead in the development of tailored treatment for breast cancer patients carrying both pol
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