In vivo imaging of protease activity by Probody therapeutic activation.

Probody™ therapeutics are recombinant, proteolytically-activated antibody prodrugs, engineered to remain inert until activated locally by tumor-associated proteases. Probody therapeutics exploit the fundamental dysregulation of extracellular protease activity that exists in tumors relative to healthy tissue. Leveraging the ability of a Probody therapeutic to bind its target at the site of disease after proteolytic cleavage, we developed a novel method for profiling protease activity in living animals. Using NIR optical imaging, we demonstrated that a non-labeled anti-EGFR Probody therapeutic can become activated and compete for binding to tumor cells in vivo with a labeled anti-EGFR monoclonal antibody. Furthermore, by inhibiting matriptase activity in vivo with a blocking-matriptase antibody, we show that the ability of the Probody therapeutic to bind EGFR in vivo was dependent on protease activity. These results demonstrate that in vivo imaging of Probody therapeutic activation can be used for screening and characterization of protease activity in living animals, and provide a method that avoids some of the limitations of prior methods. This approach can improve our understanding of the activity of proteases in disease models and help to develop efficient strategies for cancer diagnosis and treatment

Incorporating risk and uncertainty into pavement netwoek maintenance and rehabilitation budged allocation decisions

Analiza los departamentos de transporte en Estados Unidos de América, donde suelen distribuir sus presupuestos de mantenimiento en base a diversas metodologías, de acuerdo a la nueva ley MAP 21 se debe desarrollar planes de gestión de riego. En estos planes se debe establecer el riesgo de incumplimiento de los objetivos estatales con la distribución de fondos de mantenimiento y rehabilitación. El trabajo de investigación desarrollado plantea una metodología que permite cuantificar la incertidumbre y riesgo del incumplimiento de los objetivos estatales, basado en la simulación de Montecarlo y la optimización enteraTesi

Mesenchymal stem cells and their use as cell replacement therapy and disease modelling tool.

Mesenchymal stem cells (MSCs) from adult somatic tissues may differentiate in vitro and in vivo into multiple mesodermal tissues including bone, cartilage, adipose tissue, tendon, ligament or even muscle. MSCs preferentially home to damaged tissues where they exert their therapeutic potential. A striking feature of the MSCs is their low inherent immunogenicity as they induce little, if any, proliferation of allogeneic lymphocytes and antigen-presenting cells. Instead, MSCs appear to be immunosuppressive in vitro. Their multilineage differentiation potential coupled to their immuno-privileged properties is being exploited worldwide for both autologous and allogeneic cell replacement strategies. Here, we introduce the readers to the biology of MSCs and the mechanisms underlying immune tolerance. We then outline potential cell replacement strategies and clinical applications based on the MSCs immunological properties. Ongoing clinical trials for graft-versus-host-disease, haematopoietic recovery after co-transplantation of MSCs along with haematopoietic stem cells and tissue repair are discussed. Finally, we review the emerging area based on the use of MSCs as a target cell subset for either spontaneous or induced neoplastic transformation and, for modelling non-haematological mesenchymal cancers such as sarcomas

Signatures of Dark Matter Scattering Inelastically Off Nuclei

Direct dark matter detection focuses on elastic scattering of dark matter particles off nuclei. In this study, we explore inelastic scattering where the nucleus is excited to a low-lying state of 10-100 keV, with subsequent prompt de-excitation. We calculate the inelastic structure factors for the odd-mass xenon isotopes based on state-of-the-art large-scale shell-model calculations with chiral effective field theory WIMP-nucleon currents. For these cases, we find that the inelastic channel is comparable to or can dominate the elastic channel for momentum transfers around 150 MeV. We calculate the inelastic recoil spectra in the standard halo model, compare these to the elastic case, and discuss the expected signatures in a xenon detector, along with implications for existing and future experiments. The combined information from elastic and inelastic scattering will allow to determine the dominant interaction channel within one experiment. In addition, the two channels probe different regions of the dark matter velocity distribution and can provide insight into the dark halo structure. The allowed recoil energy domain and the recoil energy at which the integrated inelastic rates start to dominate the elastic channel depend on the mass of the dark matter particle, thus providing a potential handle to constrain its mass.Comment: 9 pages, 7 figures. Matches resubmitted version to Phys. Rev. D. One figure added; supplemental material (fits to the structure functions) added as an Appendi

Floral enhancement of arable field margins increases moth abundance and diversity

Moth populations have declined across large parts of north-western Europe since the mid-20th century due, in part, to agricultural intensification. Agri-environment schemes (AES) are widely implemented across Europe to protect biodiversity in agricultural landscapes. Grass field margins enriched with wildflowers typically out-perform grass-only margins in terms of increasing insect abundance and diversity. However, the effect of wildflower enrichment on moths remains largely unstudied. Here, the relative importance of larval hostplants and nectar resources for adult moths within AES field margins are investigated. Two treatments and a control were compared: (i) a plain grass mix, the control, (ii) a grass mix enriched with only moth-pollinated flowers, and (iii) a grass mix enriched with 13 wildflower species. Abundance, species richness and Shannon diversity were up to 1.4, 1.8 and 3.5 times higher, respectively, in the wildflower treatment compared to plain grass. The difference in diversity between treatments became greater in the second year. There was no difference in total abundance, richness or diversity between the plain grass treatment and grass enriched with moth-pollinated flowers. The increase in abundance and diversity in the wildflower treatment was due primarily to the provision of larval hostplants, with nectar provision playing a smaller role. The relative abundance of species whose larval hostplants included sown wildflowers increased in the second year, suggesting colonisation of the new habitat. Implications for insect conservation. We show that, at the farm scale, moth diversity can be greatly enhanced and abundance moderately enhanced by sowing diverse wildflower margins, providing these insects with both larval hostplants and floral resources, compared to grass-only margins

Do natural enemies really make a difference? Field scale impacts of parasitoid wasps and hoverfly larvae on cereal aphid populations

Naturally occurring predators and parasitoids are known to reduce the abundance of pest invertebrates in arable crops, yet current treatment thresholds do not account for such a contribution to pest management. In the present study, we provide evidence for the presence of natural enemies correlating with a subsequent reduction in pest population growth. The abundance of cereal aphid pests and two key aphidophagous natural enemies, parasitoid wasps (Aphidiinae) and hoverfly larvae (Syrphinae), was assessed at field boundaries and interiors in southeast England. The highest rate of aphid population growth was associated with locations where no natural enemies were found. The presence of either Aphidiinae wasps or predatory Syrphinae larvae was associated with a reduction in the rate of aphid population growth, irrespective of location within the field, and overall aphid population growth was negatively correlated with increasing natural enemy abundance. The results of the present study indicate that natural enemies contribute significantly to pest control, and provide further evidence supporting the use of management strategies for promoting natural enemies in agro-ecosystems. Aphid predators and parasitoids make an important contribution to aphid pest control within cereal fields, and thresholds for insecticide application should account for this to avoid unnecessary treatments

Improving Heifer Development Programs Using Precision Technology and DDGS

Study Description: Heifers were stratified into two groups based on initial body weight and each group was randomly assigned to one of two treatments: a control group (n=30) and a precision group (n=30). Treatment groups are separated into different pastures to graze dormant native range from November to April. Groups are rotated monthly to reduce individual pasture influence. Heifers in the control group are supplemented as a group and bunk fed 5lb/head/day with dried distiller grain pellets (DDGS). Heifers within the precision group will be supplemented individually using the SmartFeed system (C-Lock Inc. Rapid City, SD) and offered 5lb/head/day DDGS pellets. Individual daily weight and daily rate of gain will be measured within both groups using SmartScale technology. A time series trend analysis will be used to forecast animal BW at time of breeding, ensure individual heifer gain is satisfactory and adjust amount of supplement delivered to ensure animals are achieving target weight gains

The Implementation of Positive Behavioral Support in an Elementary School: Processes, Procedures, and Outcomes

This article presents the processes and outcomes of a year of School-Wide Positive Behavior Support in a North Texas elementary school serving kindergarten through grade 3 students. Included is a description of a school treatment package that incorporated components such as facilitation of the teaming process, a lottery-type system of intermittent reinforcement, mystery motivators, and recognition assemblies, all targeted at increased student compliance with school rules. Positive outcomes included: (a) a reduction in the number of office referrals; (b) reduced frequency of rules-based violations on the part of students; (c) reduced use of punitive consequences such as time-outs, written reprimands, and student conferences on the part of the faculty and administration; and (d) an increase in scores on a state-mandated academic achievement assessment administered to grade 3 students.Cet article présente les processus et les résultats découlant de la mise en application, pendant une année, d’un programme de gestion de classe et d’école pour contrer l’indiscipline et les conflits (SchoolWide Positive Behavior Support) dans une école primaire (maternelle-troisième) dans le nord du Texas. Nous décrivons le programme et ses composantes telles la facilitation du processus de formation d’équipes, un système ressemblant à un jeu de loterie et visant le renforcement intermittent, des facteurs motivants «mystères» et des rencontres de reconnaissance du mérite – le tout pour stimuler chez les élèves un comportement conforme aux règlements de l’école. Parmi les résultats positifs, notons : (a) une diminution du nombre d’élèves envoyés à la direction; (b) une diminution de la fréquence des infractions; (c) une diminution de l’emploi des punitions telles la suspension de renforcement, les réprimandes écrites et les conférences entre les élèves et le personnel enseignant et l’administration; et (d) une hausse des scores obtenus par les élèves en 3e aux évaluations d’état du rendement académique

Long-lived optical phonons in ZnO studied with impulsive stimulated Raman scattering

The anharmonic properties of the low-frequency E2 phonon in ZnO were measured using impulsive stimulated Raman scattering. At 5 K, the frequency and lifetime are (2.9787 +/- 0.0002) THz and (211 +/- 7) ps. The unusually long lifetime and the high accuracy in the determination of the frequency hold promise for applications in metrology, quantum computation and materials characterization. The temperature dependence of the lifetime is determined by two-phonon up-conversion decay contributions, which vanish at zero temperature. Results suggest that the lifetime is limited by isotopic disorder and that values in the nanosecond range may be achievable in isotopically-pure samples