Preliminary Clinical Evaluation of Elastic Matching System

In order to evaluate the performance of our elastic matching system, we have created a digitized atlas from a young normal male brain, using 135 myelin-stained sections at 700 micron spacing. Software was written to enter and edit regional anatomic contours, which were stacked and aligned to create a 3D atlas. We then evaluated the matching system by comparing computer generated contours with expert-defined contours for several subcortical structures, based on CT scans from six neurologically normal patients. The error in positioning, as defined by the distance between the centers of gravity, averaged 4.2 mm for the computer and 1.7 mm for the worst expert\u27s reading, with the computer-drawn region frequently inscribed within that of the expert. Comparison was also made for each structure by determining the volume of overlap and the volumes not overlapping. On average, the computer\u27s agreement with the experts was about 20% less than the agreement among the experts. This was a preliminary test of the system using only subcortical structures. The results are promising, and techniques are being implemented to overcome the current deficiencies

Rlpy: A Value-Function-Based Reinforcement Learning Framework for Education and Research

RLPy is an object-oriented reinforcement learning software package with a focus on valuefunction-based methods using linear function approximation and discrete actions. The framework was designed for both educational and research purposes. It provides a rich library of fine-grained, easily exchangeable components for learning agents (e.g., policies or representations of value functions), facilitating recently increased specialization in reinforcement learning. RLPy is written in Python to allow fast prototyping, but is also suitable for large-scale experiments through its built-in support for optimized numerical libraries and parallelization. Code profiling, domain visualizations, and data analysis are integrated in a self-contained package available under the Modified BSD License at http://github.com/rlpy/rlpy. All of these properties allow users to compare various reinforcement learning algorithms with little effort

“Really this girl ought to be going to something better” : rhoticity and social meaning in oral history data

This paper explores the shift to non-rhoticity in Oldham (UK), using oral history interviews recorded in the 1980s, with speakers born between 1893 and 1929. We first account for the linguistic constraints on /r/ use and explore macro-level social patterns, where the women were more advanced in the change. We investigate this finding further using a modified version of the Lectal Focusing in Interaction method (Sharma & Rampton 2015), tracking two speakers’ variation through the course of an interaction, and providing insight into the social meaning of rhoticity for these speakers. We suggest that, for them, rhoticity may be ideologically linked to tradition and older ways of life, and non-rhoticity may be ideologically linked to modernity and mobility, and the gender split may partly reflect the men and women’s differing orientations to these concepts. We also evaluate the effectiveness of applying modern methods, such as LFI analysis, to archival data

Sterile Testis Complementation with Spermatogonial Lines Restores Fertility to DAZL-Deficient Rats and Maximizes Donor Germline Transmission

Despite remarkable advances in assisted reproductive capabilities ∼4% of all couples remain involuntarily infertile. In almost half of these cases, a lack of conception can in some measure be attributed to the male partner, wherein de novo Y-chromosomal deletions of sperm-specific Deleted-in-Azoospermia (DAZ) genes are particularly prevalent. In the current study, long-term cultures of rat spermatogonial stem cells were evaluated after cryo-storage for their potential to restore fertility to rats deficient in the DAZ-like (DAZL) gene. Detailed histological analysis of DAZL-deficient rat testes revealed an apparently intact spermatogonial stem cell compartment, but clear failure to produce mature haploid gametes resulting in infertility. After proliferating >1 million-fold in cell number during culture post-thaw, as few as 50,000 donor spermatogonia transplanted into only a single testis/recipient effectively restored fecundity to DAZL-deficient rats, yielding 100% germline transmission to progeny by natural mating. Based on these results, the potency and efficacy of this donor stem cell line for restoring fertility to azoospermic rodents is currently unprecedented. Prospectively, similar successes in humans could be directly linked to the feasibility of obtaining enough fully functional spermatogonial stem cells from minimal testis biopsies to be therapeutically effective. Thus, regeneration of sperm production in this sterile recipient provides an advanced pre-clinical model for optimizing the efficacy of stem cell therapies to cure a paradoxically increasing number of azoospermic men. This includes males that are rendered infertile by cancer therapies, specific types of endocrine or developmental defects, and germline-specific de novo mutations; all of whom may harbor healthy sources of their own spermatogonial stem cells for treatment

Electrochemical and thermal detection of allergenic substance lysozyme with molecularly imprinted nanoparticles

Lysozyme (LYZ) is a small cationic protein which is widely used for medical treatment and in the food industry to act as an anti-bacterial agent; however, it can trigger allergic reactions. In this study, high-affinity molecularly imprinted nanoparticles (nanoMIPs) were synthesized for LYZ using a solid-phase approach. The produced nanoMIPs were electrografted to screen-printed electrodes (SPEs), disposable electrodes with high commercial potential, to enable electrochemical and thermal sensing. Electrochemical impedance spectroscopy (EIS) facilitated fast measurement (5–10 min) and is able to determine trace levels of LYZ (pM) and can discriminate between LYZ and structurally similar proteins (bovine serum albumin, troponin-I). In tandem, thermal analysis was conducted with the heat transfer method (HTM), which is based on monitoring the heat transfer resistance at the solid–liquid interface of the functionalized SPE. HTM as detection technique guaranteed trace-level (fM) detection of LYZ but needed longer analysis time compared to EIS measurement (30 min vs 5–10 min). Considering the versatility of the nanoMIPs which can be adapted to virtually any target of interest, these low-cost point-of-care sensors hold great potential to improve food safety

Next-Generation Probiotics Targeting \u3ci\u3eClostridium difficile\u3c/i\u3e through Precursor- Directed Antimicrobial Biosynthesis

Integration of antibiotic and probiotic therapy has the potential to lessen the public health burden of antimicrobial-associated diseases. Clostridium difficile infection (CDI) represents an important example where the rational design of next-generation probiotics is being actively pursued to prevent disease recurrence. Because intrinsic resistance to clinically relevant antibiotics used to treat CDI (vancomycin, metronidazole, and fidaxomicin) is a desired trait in such probiotic species, we screened several bacteria and identified Lactobacillus reuteri to be a promising candidate for adjunct therapy. Human-derived L. reuteri bacteria convert glycerol to the broad-spectrum antimicrobial compound reuterin. When supplemented with glycerol, strains carrying the pocR gene locus were potent reuterin producers, with L. reuteri 17938 inhibiting C. difficile growth at a level on par with the level of growth inhibition by vancomycin. Targeted pocR mutations and complementation studies identified reuterin to be the precursor-induced antimicrobial agent. Pathophysiological relevance was demonstrated when the codelivery of L. reuteri with glycerol was effective against C. difficile colonization in complex human fecal microbial communities, whereas treatment with either glycerol or L. reuteri alone was ineffective. A global unbiased microbiome and metabolomics analysis independently confirmed that glycerol precursor delivery with L. reuteri elicited changes in the composition and function of the human microbial community that preferentially targets C. difficile outgrowth and toxicity, a finding consistent with glycerol fermentation and reuterin production. Antimicrobial resistance has thus been successfully exploited in the natural design of human microbiome evasion of C. difficile, and this method may provide a prototypic precursor-directed probiotic approach. Antibiotic resistance and substrate bioavailability may therefore represent critical new determinants of probiotic efficacy in clinical trials

Pollution, habitat loss, fishing and climate change as critical threats to penguins

Cumulative human impacts across the world’s oceans are considerable. We therefore examined a single model taxonomic group, the penguins (Spheniscidae), to explore how marine species and communities might be at risk of decline or extinction in the southern hemisphere. We sought to determine the most important threats to penguins and to suggest means to mitigate these threats. Our review has relevance to other taxonomic groups in the southern hemisphere and in northern latitudes, where human impacts are greater. Our review was based on an expert assessment and literature review of all 18 penguin species; 49 scientists contributed to the process. For each penguin species, we considered their range and distribution, population trends, and main anthropogenic threats over the past approximately 250 years. These threats were harvesting adults for oil, skin, and feathers and as bait for crab and rock lobster fisheries; harvesting of eggs; terrestrial habitat degradation; marine pollution; fisheries bycatch and resource competition; environmental variability and climate change; and toxic algal poisoning and disease. Habitat loss, pollution, and fishing, all factors humans can readily mitigate, remain the primary threats for penguin species. Their future resilience to further climate change impacts will almost certainly depend on addressing current threats to existing habitat degradation on land and at sea. We suggest protection of breeding habitat, linked to the designation of appropriately scaled marine reserves, including in the High Seas, will be critical for the future conservation of penguins. However, large-scale conservation zones are not always practical or politically feasible and other ecosystem-based management methods that include spatial zoning, bycatch mitigation, and robust harvest control must be developed to maintain marine biodiversity and ensure that ecosystem functioning is maintained across a variety of scales.Los impactos humanos acumulativos a lo largo de los océanos del planeta son considerables. Por eso examinamos un solo modelo de grupo taxonómico, los pingüinos (Sphenischidae), para explorar cómo las especies y las comunidades marinas pueden estar en riesgo de disminuir o de extinguirse en el hemisferio sur. Buscamos determinar la amenaza más importante para los pingüinos y sugerir métodos para mitigar estas amenazas. Nuestra revisión tiene relevancia para otros grupos taxonómicos en el hemisferio sur y en las latitudes norteñas, donde los impactos humanos son mayores. Nuestra revisión se basó en una evaluación experta y una revisión de literaratura de las 18 especies de pingüinos; 49 científicos contribuyeron al proceso. Para cada especie de pingüino, consideramos su rango y distribución, tendencias poblacionales y las principales amenazas antropogénicas en aproximadamente los últimos 250 años. Estas amenazas fueron la captura de adultos para obtener aceite, piel y plumas y el uso como carnada para la pesca de cangrejos y langostas: la recolección de huevos; la degradación del hábitat terrestre; la contaminación marina; la pesca accesoria y la competencia por recursos; la variabilidad ambiental y el cambio climático; y el envenenamiento por algas tóxicas y enfermedades. La pérdida de hábitat, la contaminación y la pesca, todos factores que los humanos pueden mitigar, siguen siendo las amenazas principales para las especies de pingüinos. Su resiliencia futura a más impactos por cambio climático dependerá certeramente de que nos enfoquemos en las amenazas actuales a la degradación de hábitats existentes en tierra y en el mar. Sugerimos que la protección de hábitats de reproducción, en conjunto con la designación de reservas marinas de escala apropiada, incluyendo alta mar, será crítica para la conservación futura de los pingüinos. Sin embargo, las zonas de conservación a gran escala no son siempre prácticas o políticamente viables, y otros métodos de manejo basados en ecosistemas que incluyen la zonificación espacial, la mitigación de captura accesoria, y el control fuerte de captura deben desarrollarse para mantener la biodiversidad marina y asegurar que el funcionamiento de los ecosistemas se mantenga a lo largo de una variedad de escalas.Fil: Trathan, Phil N.. British Antartic Survey; Reino UnidoFil: Garcia Borboroglu, Jorge Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Nacional Patagónico; ArgentinaFil: Boersma, P. Dee. University of Washington; Estados UnidosFil: Bost, Charles André. Centre d´Etudes Biologiques de Chizé; FranciaFil: Crawford, Robert J. M.. Department of Environmental Affairs; SudáfricaFil: Crossin, Glenn T.. Dalhousie University Halifax; CanadáFil: Cuthbert, Richard. Royal Society for the Protection of Birds; Reino UnidoFil: Dann, Peter. Phillip Island Nature Parks; AustraliaFil: Davis, Lloyd Spencer. University Of Otago; Nueva ZelandaFil: de la Puente, Santiago. Universidad Cayetano Heredia; PerúFil: Ellenberg, Ursula. University Of Otago; Nueva ZelandaFil: Lynch, Heather J.. Stony Brook University; Estados UnidosFil: Mattern, Thomas. University Of Otago; Nueva ZelandaFil: Pütz, Klemens. Antarctic Research Trust; AlemaniaFil: Seddon, Philip J.. University Of Otago; Nueva ZelandaFil: Trivelpiece, Wayne. Southwest Fisheries Science Center; Estados UnidosFil: Wienecke, Bárbara. Australian Antarctic Division; Australi