Successfully navigating the valley of death: the importance of accelerators to support academic drug discovery and development.

Introduction: The drug discovery and development 'valley of death' remains a challenge for promising new therapies originating from academic research laboratories. Drug discovery support centers and accelerators have been established to provide monetary and scientific support, but limited available funding along with cultural and expertise gaps remain obstacles for many promising technologies.

Areas Covered: In this meta-opinion article, the authors summarize the literature around obstacles that academic drug discovery projects face, along with potential solutions and best practices.

SURVEILLANCE FOR AN EMERGENT HOOF DISEASE IN ELK (CERVUS ELAPHUS) IN THE US PACIFIC WEST SUPPLEMENTED BY 16S RRNA GENE AMPLICON SEQUENCING.

A novel hoof disease of elk (Cervus elaphus) was described in southwestern Washington, US, in 2008 and was subsequently diagnosed in an adjacent area in northwestern Oregon in 2014. The disease, currently referred to as treponeme-associated hoof disease (TAHD), is characterized by lesions ranging from mild erosions, to severe ulcers with underrunning of the hoof capsule and heel-sole junction, to overgrown and avulsed hoof capsules. Histologically, lesions exhibit epithelial erosion or ulceration, suppurative inflammation, and the presence of argyrophilic spirochetes.

Traceback of the outbreak in British Columbian bighorn sheep ().

are a non-burrowing, ectoparasitic, mange-causing mite that has been documented in American bighorn sheep populations throughout the 19th and 20th centuries; however, it was not seen on Canadian bighorn sheep until 2006. The aim of this study was to determine the potential source of the outbreak in Canadian bighorn sheep. Morphological and molecular analyses were used to compare mites recovered from outbreak-associated bighorn sheep, pet rabbits in Canada, and on historically infested bighorn sheep in the USA.

and human hexokinases share similar active sites but display distinct quaternary architectures.

Malaria is a devastating disease caused by a protozoan parasite. It affects over 300 million individuals and results in over 400 000 deaths annually, most of whom are young children under the age of five. Hexokinase, the first enzyme in glucose metabolism, plays an important role in the infection process and represents a promising target for therapeutic intervention.

Providing a Single Ground-Truth for Illuminant Estimation for the ColorChecker Dataset.

The ColorChecker dataset is one of the most widely used image sets for evaluating and ranking illuminant estimation algorithms. However, this single set of images has at least 3 different sets of ground-truth (i.e.

Methylomic correlates of autophagy activity in cystic fibrosis.

Autophagy is a highly regulated, biological process that provides energy during periods of stress and starvation. This conserved process also acts as a defense mechanism and clears microbes from the host cell. Autophagy is impaired in Cystic Fibrosis (CF) patients and CF mice, as their cells exhibit low expression levels of essential autophagy molecules.

Learning to Detect Blue-White Structures in Dermoscopy Images With Weak Supervision.

We propose a novel approach to identify one of the most significant dermoscopic criteria in the diagnosis of cutaneous Melanoma: the blue-white structure (BWS). In this paper, we achieve this goal in a multiple instance learning (MIL) framework using only image-level labels indicating whether the feature is present or not. To this aim, each image is represented as a bag of (nonoverlapping) regions, where each region may or may not be identified as an instance of BWS.

Potential disease agents in domestic goats and relevance to bighorn sheep (Ovis canadensis) management.

Domestic goats are raised for meat, milk and hair production, in herds for rangeland weed control, and as pack animals. Domestic sheep, goats and wild bighorn sheep are all susceptible to a multifactorial pneumonia. We sampled 43 herd goats from 7 herds and 48 pack goats from 11 herds for viral and bacterial serology, parasitology, and Pasteurellaceae microbiology.

Incorporating Colour Information for Computer-Aided Diagnosis of Melanoma from Dermoscopy Images: A Retrospective Survey and Critical Analysis.

Cutaneous melanoma is the most life-threatening form of skin cancer. Although advanced melanoma is often considered as incurable, if detected and excised early, the prognosis is promising. Today, clinicians use computer vision in an increasing number of applications to aid early detection of melanoma through dermatological image analysis (dermoscopy images, in particular).

Identification of Novel Plasmodium falciparum Hexokinase Inhibitors with Antiparasitic Activity.

Plasmodium falciparum, the deadliest species of malaria parasites, is dependent on glycolysis for the generation of ATP during the pathogenic red blood cell stage. Hexokinase (HK) catalyzes the first step in glycolysis, transferring the γ-phosphoryl group of ATP to glucose to yield glucose-6-phosphate. Here, we describe the validation of a high-throughput assay for screening small-molecule collections to identify inhibitors of the P.

Genomics reveals historic and contemporary transmission dynamics of a bacterial disease among wildlife and livestock.

Whole-genome sequencing has provided fundamental insights into infectious disease epidemiology, but has rarely been used for examining transmission dynamics of a bacterial pathogen in wildlife. In the Greater Yellowstone Ecosystem (GYE), outbreaks of brucellosis have increased in cattle along with rising seroprevalence in elk. Here we use a genomic approach to examine Brucella abortus evolution, cross-species transmission and spatial spread in the GYE.

Spectral edge: gradient-preserving spectral mapping for image fusion.

This paper describes a novel approach to image fusion for color display. Our goal is to generate an output image whose gradient matches that of the input as closely as possible. We achieve this using a constrained contrast mapping paradigm in the gradient domain, where the structure tensor of a high-dimensional gradient representation is mapped exactly to that of a low-dimensional gradient field which is then reintegrated to form an output.

Patient-clinician concordance, face-time and access.

Purpose: People in socially disadvantageous positions may receive less time with their clinicians and consequently reduced access to healthcare resources, potentially magnifying health disparities. Socio-cultural characteristics of clinicians and patients may influence the time spent together. The purpose of this paper is to explore the relationship between clinician/patient time and clinician and patient characteristics using real-time location systems (RTLS).

A probabilistic approach to quantification of melanin and hemoglobin content in dermoscopy images.

We describe a technique that employs the stochastic Latent Topic Models framework to allow quantification of melanin and hemoglobin content in dermoscopy images. Such information bears useful implications for analysis of skin hyperpigmentation, and for classification of skin diseases. The proposed method outperforms existing approaches while allowing for more stringent and probabilistic modeling than previously.

Exemplar-Based Color Constancy and Multiple Illumination.

Exemplar-based learning or, equally, nearest neighbor methods have recently gained interest from researchers in a variety of computer science domains because of the prevalence of large amounts of accessible data and storage capacity. In computer vision, these types of technique have been successful in several problems such as scene recognition, shape matching, image parsing, character recognition, and object detection. Applying the concept of exemplar-based learning to the problem of color constancy seems odd at first glance since, in the first place, similar nearest neighbor images are not usually affected by precisely similar illuminants and, in the second place, gathering a dataset consisting of all possible real-world images, including indoor and outdoor scenes and for all possible illuminant colors and intensities, is indeed impossible.

Face time versus test ordering: is there a trade-off?

Background: As clinician-patient face time comes under pressure, clinicians might consider substituting testing for time spent in diagnostic reasoning, history, and physical exam.

Objectives: To explore the relationship between clinician-patient time and medical resource utilization.

Methods: In the Massachusetts General Hospital/Massachusetts General Physician Organization outpatient radio frequency identification project, clinicians and patients wore real-time location system (RTLS) tags.

Automatic detection of blue-white veil by discrete colour matching in dermoscopy images.

Skin lesions are often comprised of various colours. The presence of multiple colours with an irregular distribution can signal malignancy. Among common colours under dermoscopy, blue-grey (blue-white veil) is a strong indicator of malignant melanoma.

Mechanisms of cellular invasion by intracellular parasites.

Numerous disease-causing parasites must invade host cells in order to prosper. Collectively, such pathogens are responsible for a staggering amount of human sickness and death throughout the world. Leishmaniasis, Chagas disease, toxoplasmosis, and malaria are neglected diseases and therefore are linked to socio-economical and geographical factors, affecting well-over half the world's population.

Plasmodium falciparum erythrocytic stage parasites require the putative autophagy protein PfAtg7 for normal growth.

Analysis of the Plasmodium falciparum genome reveals a limited number of putative autophagy genes, specifically the four genes involved in ATG8 lipidation, an essential step in formation of autophagosomes. In yeast, Atg8 lipidation requires the E1-type ligase Atg7, an E2-type ligase Atg3, and a cysteine protease Atg4. These four putative P.

Interrogating a hexokinase-selected small-molecule library for inhibitors of Plasmodium falciparum hexokinase.

Parasites in the genus Plasmodium cause disease throughout the tropic and subtropical regions of the world. P. falciparum, one of the deadliest species of the parasite, relies on glycolysis for the generation of ATP while it inhabits the mammalian red blood cell.

Intrinsic melanin and hemoglobin colour components for skin lesion malignancy detection.

In this paper we propose a new log-chromaticity 2-D colour space, an extension of previous approaches, which succeeds in removing confounding factors from dermoscopic images: (i) the effects of the particular camera characteristics for the camera system used in forming RGB images; (ii) the colour of the light used in the dermoscope; (iii) shading induced by imaging non-flat skin surfaces; (iv) and light intensity, removing the effect of light-intensity falloff toward the edges of the dermoscopic image. In the context of a blind source separation of the underlying colour, we arrive at intrinsic melanin and hemoglobin images, whose properties are then used in supervised learning to achieve excellent malignant vs. benign skin lesion classification.

8,8-dialkyldihydroberberines with potent antiprotozoal activity.

Semisynthetic 8,8-dialkyldihydroberberines (8,8-DDBs) were found to possess mid- to low-nanomolar potency against Plasmodium falciparum blood-stage parasites, Leishmania donovani intracellular amastigotes, and Trypanosoma brucei brucei bloodstream forms. For example, 8,8-diethyldihydroberberine chloride (5b) exhibited in vitro IC50 values of 77, 100, and 5.3 nM against these three parasites, respectively.

Guidelines for the use and interpretation of assays for monitoring autophagy.

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding.

Pasteurellaceae isolated from bighorn sheep (Ovis canadensis) from Idaho, Oregon, and Wyoming.

Objective: To elucidate the species and biovariants of Pasteurellaceae isolated from clinically normal bighorn sheep (Ovis canadensis) or bighorn sheep with evidence of respiratory disease.

Sample: 675 Pasteurellaceae isolates from 290 free-ranging bighorn sheep in Idaho, Oregon and Wyoming.

Procedures: Nasal and oropharyngeal swab specimens were inoculated onto selective and nonselective blood agar media.

Detection of Mycoplasma ovipneumoniae and M. arginini in bighorn sheep using enrichment culture coupled with genus- and species-specific polymerase chain reaction.

Mycoplasma species are of interest as possible primary pathogens in the pneumonia complex of bighorn sheep (Ovis canadensis). Previous investigations have not commonly detected low frequencies of Mycoplasma spp. from free-ranging bighorn sheep, possibly due to the fastidious and slow growth of these organisms.