The rule of five should not impede anti-parasitic drug development.

The "rule of 5" has become a mainstay of decision-making in the pharmaceutical industry as well as in nonindustrial (academic and institutional) drug development. However the authors of the original paper never intended for "double cutoffs" to preclude development of new drug leads for parasitic diseases

The Dynamic and Multi-Dimensional Process of Foundations

Process is an intrinsic part of art and design. This panel will investigate how process is approached in the Foundations program. Panel members will present successful examples of stages of processes containing concept and technical developments that lead to a satisfying product

Using P-band Signals of Opportunity Radio Waves for Root Zone Soil Moisture Remote Sensing

Retrieval of Root Zone Soil Moisture (RZSM) is important for understanding the carbon cycle for use in climate change research as well as meteorology, hydrology, and precision agriculture studies. A current method of remote sensing, GNSS-R uses GPS signals to measure soil moisture content and vegetation biomass, but it is limited to 3-5 cm of soil penetration depth. Signals of Opportunity (SoOp) has emerged as an extension of GNSS-R remote sensing using communication signals. P-band communication signals (370 MHz) will be studied as an improved method of remote sensing of RZSM. P-band offers numerous advantages over GNSS-R, including stronger signal strength and deeper soil penetration. A SoOp instrument was installed on a mobile antenna tower in a farm field at Purdue University in West Lafayette, IN. An additional half-wave dipole antenna, as well as corresponding modifications to the experiment’s front-end box, was included to capture horizontally-polarized reflected P-band signals throughout a corn growth season. By measuring the reflected signal power off the soil over time, soil moisture and above-ground biomass can be measured. Soil moisture and vegetation biomass change the soil’s dielectric reflection coefficient and thus affect its reflectivity properties. It is expected that there will be strong correlation between reflected signal strength and soil moisture. Data will be compared against soil moisture measurements from in-situ soil sensors. The data obtained will be used to verify existing analytical soil moisture and above-ground biomass models. In addition, these results will be used to build an airborne and/or space-based remote sensing instrument

Inductive queries for a drug designing robot scientist

It is increasingly clear that machine learning algorithms need to be integrated in an iterative scientific discovery loop, in which data is queried repeatedly by means of inductive queries and where the computer provides guidance to the experiments that are being performed. In this chapter, we summarise several key challenges in achieving this integration of machine learning and data mining algorithms in methods for the discovery of Quantitative Structure Activity Relationships (QSARs). We introduce the concept of a robot scientist, in which all steps of the discovery process are automated; we discuss the representation of molecular data such that knowledge discovery tools can analyse it, and we discuss the adaptation of machine learning and data mining algorithms to guide QSAR experiments

Absorption of Short-Pulsed Laser Radiation in Superficial Human Tissues: Transient Vs Quasi-Steady Radiative Transfer

Transient radiative transfer effects are pertinent to thermal treatment of superficial cancer via short-pulsed laser irradiation. The transient effects become particularly important due to relatively strong scattering and long attenuation path of radiation in human tissues in the therapeutic window until the complete absorption. Our analysis is based on transport approximation for scattering phase function and the Monte Carlo method for radiative transfer. One-dimensional radiative transfer problem is considered, which was proved to be applicable for simulation of heat transfer and thermal destruction of tumors in superficial human tissues in the case of indirect heating strategy. A series of Monte Carlo calculations enables us to find the threshold of the steady-state approach applicability. In the biomedical problem under consideration, the steady-state solution for absorbed radiation power is sufficiently accurate at duration of laser pulse more than about 10 ps. The calculations for human tissues with embedded gold nanoshells, which are used to increase the local volumetric absorption of the radiation, showed that overheating of the nanoshells with respect to the ambient biological tissue is strongly dependent of the laser pulse duration. This effect is quantified for short pulses by solving the unsteady radiative transfer problem

The Tabby cat locus maps to feline chromosome B1.

The Tabby markings of the domestic cat are unique coat patterns for which no causative candidate gene has been inferred from other mammals. In this study, a genome scan was performed on a large pedigree of cats that segregated for Tabby coat markings, specifically for the Abyssinian (Ta-) and blotched (tbtb) phenotypes. There was linkage between the Tabby locus and eight markers on cat chromosome B1. The most significant linkage was between marker FCA700 and Tabby (Z = 7.56, theta = 0.03). Two additional markers in the region supported linkage, although not with significant LOD scores. Pairwise analysis of the markers supported the published genetic map of the cat, although additional meioses are required to refine the region. The linked markers cover a 17-cM region and flank an evolutionary breakpoint, suggesting that the Tabby gene has a homologue on either human chromosome 4 or 8. Alternatively, Tabby could be a unique locus in cats

Chokka squid on the Agulhas Bank: life history and ecology

Available knowledge is reviewed and new data incorporated in a synthesis of the life history and ecology of the chokka squid Loligo vulgaris reynaudii. We attempt to show that these aspects are essential to rational management of the resource. The life cycle is descriptionbed in detail from the egg to adult stage, mainly in biological terms, including a comprehensive descriptionption of maturation, migration and reproduction. Possible ecological interactions, particularly those of paralarvae and copepods, are discussed. Predator-prey relationships and the current state of knowledge on the effect of the physical environment on squid availability and abundance are summarized

Phenotypic divergence despite high gene flow in Chokka squid Loligo reynaudii (Cephalopoda: Loliginidae): implications for fishery management

The commercially important chokka squid Loligo reynaudii occurring in South African waters is currently managed on a single-unit stock hypothesis. We tested this assumption through a spatial comparison of the morphology throughout the distributional range of the species. Forty-three morphometric characters were measured from 1079 chokka collected off the south coast of South Africa, the west coast of South Africa, and southern Angola. While no significant differences were found in the hard body parts, results from classification analysis showed that though all four types of morphometric attributes (soft body parts, beaks, statoliths, sucker rings) resulted in some separation, the most consistent separation of samples from the three regions was based on soft body part morphometric characters. On average, though dependent on the model, the overall correct classification rate ranged from 0.68?0.99 for males and 0.7?0.99 for females in all three regions. Previous DNA analysis had revealed some genetic differences between west coast and south coast samples, suggesting the confluence of the cold Benguela and warm Agulhas current may act as the approximate point of a phenotypic and possible genetic breakpoint. Finer scale genetic analysis of samples collected across the Benguela?Agulhas confluence reported no significant genetic structuring in this area suggesting environmental heterogeneity and not restriction of genetic flow/isolation as the primary driver of the observed phenotypic divergence.authorsversionPeer reviewe

Characteristics of survivors: growth and nutritional condition of early stages of the hake species Merluccius paradoxus and M. capensis in the southern Benguela ecosystem

Larval mortality in marine fish is strongly linked to characteristic traits such as growth and condition, but the variability in these traits is poorly understood. We tried to identify the variability in growth in relation to conditions leading to greater survival chances for early stages of Cape hake, Merluccius paradoxus and M. capensis, in the Benguela upwelling ecosystem. During two cruises in 2007 and one cruise in 2008, hake larvae and juveniles were caught. Otolith microstructures revealed a larval age ranging from 2 to 29 days post-hatching (dph), whereas juvenile age was 67–152 dph. RNA:DNA ratios, used to evaluate nutritional condition, were above the relevant threshold level for growth. No strong coupling between growth and condition was detected, indicating a complex relationship between these factors in the southern Benguela ecosystem. Merluccius paradoxus juveniles caught in 2007 (the surviving larvae of 2006) had significantly higher larval growth rates than larvae hatched in 2007 and 2008, possibly indicating selection for fast growth in 2006. High selection pressure on growth could be linked to predation avoidance, including cannibalism