CAR T cells for T-cell leukemias: Insights from mathematical models

Immunotherapy has the potential to change the way all cancer types are treated and cured. Cancer immunotherapies use elements of the patient immune system to attack tumor cells. One of the most successful types of immunotherapy is CAR-T cells. This treatment works by extracting patient's T-cells and adding to them an antigen receptor allowing tumor cells to be recognized and targeted. These new cells are called CAR-T cells and are re-infused back into the patient after expansion in-vitro. This approach has been successfully used to treat B-cell malignancies (B-cell leukemias and lymphomas). However, its application to the treatment of T-cell leukemias faces several problems. One of these is fratricide, since the CAR-T cells target both tumor and other CAR-T cells. This leads to nonlinear dynamical phenomena amenable to mathematical modeling. In this paper we construct a mathematical model describing the competition of CAR-T, tumor and normal T-cells and studied some basic properties of the model and its practical implications. Specifically, we found that the model reproduced the observed difficulties for in-vitro expansion of the therapeutic cells found in the laboratory. The mathematical model predicted that CAR-T cell expansion in the patient would be possible due to the initial presence of a large number of targets. We also show that, in the context of our mathematical approach, CAR-T cells could control tumor growth but not eradicate the disease

Seasonal nutrient dynamics and biomass quality of giant reed (Arundo donax L.) and miscanthus (Miscanthus x giganteus Greef et Deuter) as energy crops

The importance of energy crops in displacing fossil fuels within the energy sector in Europe is growing. Among energy crops, the use of perennial rhizomatous grasses (PRGs) seems promising owing to their high productivity and their nutrient recycling that occurs during senescence. In particular, nutrient requirements and biomass quality have a fundamental relevance to biomass systems efficiency. The objective of our study was to compare giant reed (Arundo donax L.) and miscanthus (Miscanthus × giganteus Greef et Deuter) in terms of nutrient requirements and cellulose, hemicelluloses and lignin content. This aim was to identify, in the Mediterranean environment, the optimal harvest time that may combine, beside a high biomass yield, high nutrient use efficiency and a good biomass quality for second generation biofuel production. The research was carried out in 2009, in San Piero a Grado, Pisa (Central Italy; latitude 43°41' N, longitude 10°21' E), on seven-year-old crops in a loam soil characterised by good water availability. Maximum above-ground nutrient contents were generally found in summer. Subsequently, a decrease was recorded; this suggested a nutrient remobilisation from above-ground biomass to rhizomes. In addition, miscanthus showed the highest N, P, and K use efficiency, probably related to its higher yield and its C4 pathway. Regarding biomass quality, stable values of cellulose (38%), hemicelluloses (25%) and lignin (8%) were reported from July onwards in both crops. Hence, these components appear not to be discriminative parameters in the choice of the harvest time in the Mediterranean environment. In conclusion, our results highlighted that, in our environment, a broad harvest period (from late autumn to winter) seems suitable for these PRGs. However, further research is required to evaluate the role of rhizomes in nutrient storage and supply during the growing season, as well as ecological and productive performances in marginal lands, in particular those where water availability may be a limiting factor

Two years monitoring of soil N2O emissions on durum wheat in a Mediterranean area: the effect of tillage intensity and N-fertilizer rate

Two years monitoring of soil N2O emissions on durum wheat in a Mediterranean area: the effect of tillage intensity and N-fertilizer rate. EGU General Assembly 2016 Conference Abstracts, European Geophysical Unio

Tolerabilidad del resveratrol y efectos sobre parámetros bioquímicos sanguíneos

El resveratrol es un polifenol aislado de la uva al cual se le ha adjudicado actividad terapéutica antitumoral, incremento de longevidad, disminución de peso y protección cardiovascular. Se encuentra disponible como suplemento alimenticio y se vende sin prescripción médica. Evaluar la tolerabilidad de resveratrol, efectos adversos y efectos sobre pruebas de función hepática, renal y perfil de lípidos. Se administró resveratrol 500 mg, vía oral a 8 sujetos sanos durante 30 días y se realizó evaluación clínica, perfil bioquímico y de lípidos al inicio y final del estudio. No se observaron efectos adversos ni alteración en el perfil bioquímico ni de lípidos. El resveratrol fue bien tolerado, mostró ser seguro en dosis diarias de 500 mg, sin embargo se requieren estudios con mayor número de sujetos para confirmarl

Pengaruh Konsentrasi Penginduksi Metanol Serta"sumber Karbon Sorbitol Dan Monitol Terhadap Produksi A-amilase Saccharomycopsis Fibuligera R64 Dalam Pichia Pastoris

Pichia pastoris has been widely used as host for heterologous protein expression for commercial purposes. The advantages of P. pastoris as protein expression host is its ability to grow with high cell density and the presence of a gene promoter that canbe induced tightly, named AOXI encoding alcohol oxidase. Improvement of recombinant protein production under control of AOXI promoter in P. pastoris expression system is still a major concern. Optimization of methanol concentration as inducerand addition of carbon sources, is one of the strategies to improve the expression level. This research aims to study the effect of methanol as inducer as well as sorbitol and mannitol as additional carbon source to the expression level of recombinantSaccharomycopsis fibuligera a-amylase (Sfamy) by P. pastoris (Mut). Sorbitol and manuot known as non-repressive carbon source, to increase the growth ofP. past oris, but not inhibit the AOX1 promoter and foreign proteins expression. Sfamy was expressed in P. pastoris GS115 (His-, Mut) with addition ofcarbon source, sorbitol and mannitol saparately to the expression medium. The result showed that, the optimum concentration" of methanol inducer for Sfamy production is 0.75%. The addition of sorbitol or mannitol increased Sfamy production. Concentrations of sorbitol and mannitol 2% with0.75% methanol inducer increase the secretion level of recombinant Sfamy 2.13 times and 1.94 times respectively, compared with no additional carbon source. This result indicated that addition of carbon source can improved recombinant protein production by P. pastoris, and the used of sorbitol as additionalcarbon source is more effective compared to mannitol

Structural Phase Transition and Superconductivity in 2H-BaGaGe with Buckled Honeycomb Layers

We report on the structural and superconducting properties of the intermetallic compound BaGaGe. We find that this material undergoes a structural second-order phase transition from the distorted AlB$_2$-type structure (1H, $a$ = 4.3254(2) \r{A}, $c$ = 5.1078(3) \r{A}, P6/mmm) into the CaIn$_2$-type structure (2H, $a$ = 4.3087(3) \r{A}, $c$ = 10.2117(6) \r{A}, P6$_3$/mmc) at a transition temperature of $T_{\rm S}$ = 253 K. We find that the structural phase-transition corresponds to a coherent buckling of the honeycomb layers, which we can interpret as a disorder-to-order transition of the atoms located within this layer. We show that the 2H-BaGaGe phase becomes superconducting at a critical temperature of $T_{\rm c}$ = 2.1 K. The bulk nature of the superconductivity in 2H-BaGaGe is confirmed by means of specific heat measurements, where we determine a value of $\Delta C$/$\gamma T_{\rm c}$ = 1.59, which is close to the expected BCS value in the weak coupling limit

Asymmetric Inheritance of Aggregated Proteins and Age Reset in Yeast Are Regulated by Vac17-Dependent Vacuolar Functions

SummaryAge can be reset during mitosis in both yeast and stem cells to generate a young daughter cell from an aged and deteriorated one. This phenomenon requires asymmetry-generating genes (AGGs) that govern the asymmetrical inheritance of aggregated proteins. Using a genome-wide imaging screen to identify AGGs in Saccharomyces cerevisiae, we discovered a previously unknown role for endocytosis, vacuole fusion, and the myosin-dependent adaptor protein Vac17 in asymmetrical inheritance of misfolded proteins. Overproduction of Vac17 increases deposition of aggregates into cytoprotective vacuole-associated sites, counteracts age-related breakdown of endocytosis and vacuole integrity, and extends replicative lifespan. The link between damage asymmetry and vesicle trafficking can be explained by a direct interaction between aggregates and vesicles. We also show that the protein disaggregase Hsp104 interacts physically with endocytic vesicle-associated proteins, such as the dynamin-like protein, Vps1, which was also shown to be required for Vac17-dependent sequestration of protein aggregates. These data demonstrate that two physiognomies of aging—reduced endocytosis and protein aggregation—are interconnected and regulated by Vac17

Productivity of giant reed (Arundo donax L.) and miscanthus (Miscanthus x giganteus Greef et Deuter) as energy crops: growth analysis

The growing interest in bioenergy crops is leading to the development of new research aims. In fact, there is a lack of knowledge of most of these crops in terms of suitability to specific environmental conditions and of biotic and abiotic influences. The objective of our study was to compare giant reed ( Arundo donax L.) and miscanthus ( Miscanthus × giganteus Greef et Deuter), two promising lignocellulosic energy crops in Southern Europe, in terms of productivity, through growth analysis, in order to understand environmental and/or management constraints to crop development. Our research was carried out in 2009, in San Piero a Grado, Pisa (Central Italy; latitude 43°41' N, longitude 10°21' E), on a seven-year-old crop, in loam soil characterised by good nutrient and water availability. Results confirmed high yields in both species, about 40 t/ha/yr in miscanthus and 30 t/ha/yr in giant reed, achieved in the second half of October. Different growth strategies were noted as miscanthus developed a greater number of stems per square meter and higher stems, although it showed minor basal stem diameter and leaf area changes. In addition, the physiological difference between crop pathways (C3 in giant reed vs C4 in miscanthus) in a non-limiting environment allowed miscanthus to perform better. As a result, the choice of the proper crop has to be made in order to obtain maximum yield levels, minimising external inputs and optimising the land use

Prevalencia y factores asociados con deficiencia de vitamina D en una población adulta joven de dos instituciones de educación superior en Cali y Bogotá: estudio de corte transversal

La deficiencia de vitamina D es considerado un problema de salud pública. Aunque algunos estudios han evaluado la deficiencia de vitamina D en poblaciones de riesgo (adultos mayores, posmenopáusicas), existen pocos datos en población adulta joven y mucho menos en poblaciones latinoamericanas. Se realizó un estudio de corte transversal con 205 universitarios entre 18 y 45 años en 2 ciudades colombianas para establecer la prevalencia y los factores asociados con la deficiencia de vitamina D. Se consideró como deficiencia de vitamina D un valor menor o igual de 20 ng/mL de 25-hidroxivitamina-D. Se estableció una prevalencia de deficiencia de vitamina D del 22,4 % (IC 95 % 17- 29). Se encontró que el género masculino y fototipo Fitzpatrick IV se asociaron de manera independiente con mayor riesgo de deficiencia de vitamina D, mientras el consumo de pescado y la exposición al sol de miembros inferiores al hacer ejercicio lo disminuyeron

LIFE+IPNOA mobile prototype for the monitoring of soil N2O emissions from arable crops: First-year results on durum wheat

Agricultural activities are co-responsible for the emission of the most important greenhouse gases: carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O). Development of methodologies to improve monitoring techniques for N2O are still needful. The LIFE+IPNOA project aims to improve the emissions monitoring of nitrous oxide from agricultural soils and to identify the agricultural practices that can limit N2O production. In order to achieve this objective, both a mobile and a stationary instrument were developed and validated. Several experimental field trials were set up in two different sites investigating the most representative crops of Tuscany (CentralItaly), namely durum wheat, maize, sunflower, tomato and faba bean. The field trials were realized in order to test the effect on N2O emissions of key factors: tillage intensity, nitrogen fertiliser rate and irrigation. The field trial on durum wheat was set up in 2013 to test the effect of tillage intensity (minimum and conventional tillage) and nitrogen fertilisation rate (0, 110, 170 kg N ha–1) on soil N2O flux. Monitoring was carried out using the IPNOA mobile prototype. Preliminary results on N2O emissions for the durum wheat growing season showed that mean daily N2O fluxes ranged from –0.13 to 6.43 mg m–2 day–1 and cumulative N2O-N emissions over the period ranged from 827 to 2340 g N2O-N ha–1. Tillage did not affect N2O flux while increasing nitrogen fertilisation rate resulted to significantly increase N2O emissions. The IPNOA mobile prototype performed well during this first year of monitoring, allowing to catch both very low fluxes and peaks on N2O emissions after nitrogen supply, showing a good suitability to the field conditions