New interleukin-15 superagonist (IL-15SA) significantly enhances graft-versus-tumor activity.

Interleukin-15 (IL-15) is a potent cytokine that increases CD8+ T and NK cell numbers and function in experimental models. However, obstacles remain in using IL-15 therapeutically, specifically its low potency and short in vivo half-life. To help overcome this, a new IL-15 superagonist complex comprised of an IL-15N72D mutation and IL-15RαSu/Fc fusion (IL-15SA, also known as ALT-803) was developed. IL-15SA exhibits a significantly longer serum half-life and increased in vivo activity against various tumors. Herein, we evaluated the effects of IL-15SA in recipients of allogeneic hematopoietic stem cell transplantation. Weekly administration of IL-15SA to transplant recipients significantly increased the number of CD8+ T cells (specifically CD44+ memory/activated phenotype) and NK cells. Intracellular IFN-γ and TNF-α secretion by CD8+ T cells increased in the IL-15SA-treated group. IL-15SA also upregulated NKG2D expression on CD8+ T cells. Moreover, IL-15SA enhanced proliferation and cytokine secretion of adoptively transferred CFSE-labeled T cells in syngeneic and allogeneic models by specifically stimulating the slowly proliferative and nonproliferative cells into actively proliferating cells.We then evaluated IL-15SA\u27s effects on anti-tumor activity against murine mastocytoma (P815) and murine B cell lymphoma (A20). IL-15SA enhanced graft-versus-tumor (GVT) activity in these tumors following T cell infusion. Interestingly, IL-15 SA administration provided GVT activity against A20 lymphoma cells in the murine donor leukocyte infusion (DLI) model without increasing graft versus host disease. In conclusion, IL-15SA could be a highly potent T- cell lymphoid growth factor and novel immunotherapeutic agent to complement stem cell transplantation and adoptive immunotherapy

Attempts to eradicate two Pelargonium viruses (PFBV and PLPV) by meristem culture and shoot-tip cryotherapy

Attempts to eradicate the Pelargonium flower break virus (PFBV) and Pelargonium line pattern virus (PLPV) by meristem culture and apex “droplet-vitrification” cryopreservation was carried out using 5 different cultivars. A simple meristem culture did not permit to eliminate PFBV and only 15% of Pelargonium x hortorum ‘Stellar Artic’ plants regenerated from meristems was PLPV-ELISA-negative. Plants regenerated from cryopreserved apices were tested by DAS-ELISA after a 3-month growing period. Viruses were not detected in 25 and 50% of the tested plants for PFBV and PLPV respectively. Immunolocalisations were carried out for virus localisation in apices from greenhouse plants (control) and vitroplants regenerated after meristem culture or cryopreservation. Immunolocalisations realised on control explants excised from DAS-ELISA positive plants showed that PFBV and PLPV were present in the apices, even in the meristematic dome. However, viral particles were more numerous in the cells of the basal zone than in the more meristematic ones. Immunolocalisations realised on apices from the DAS-ELISA negative cryoregenerated plants showed the viruses were still present. Our results firstly demonstrated that PFBV and PLPV are even present inside meristematic cells and secondly that cryopreservation could decrease their amount in Pelargonium plants but without eliminating them totally. More knowledge on virus behaviour during cryopreservation processes could optimize the management of genetic resources using this conservation method

Self Esteem dengan Perilaku Merokok Siswa

This research is a correlation analysis with quantitative approach. The study aims to discribe the assosiation of level relationship between self-esteem and smoking behavior of students in SMK Negeri 2 Soe. Samples were male students of SMK Negeri 2 Soe numbering 70 students. Data was collected by using a scale of self-esteem and smoking behavior questionnaire and then use computer programs for data analysis. Hypothesis testing using Pearson produck moment correlation test to see the correlation between the two variables. The results show the value of the correlation coefficient of -0.333 with a significance value (p) of 0.005 which means Ha accepted that there is a relationship between self-esteem and smoking behavior of students in State Vocational High School 2 Soe

Constraining X-ray variability of the blazar 3C 273 using XMM-Newton observations over two decades

Blazars exhibit relentless variability across diverse spatial and temporal frequencies. The study of long- and short-term variability properties observed in the X-ray band provides insights into the inner workings of the central engine. In this work, we present timing and spectral analyses of the blazar 3C 273 using the X-ray observations from the $\textit{XMM-Newton}$ telescope covering the period from 2000 to 2020. The methods of timing analyses include estimation of fractional variability, long- and short-term flux distribution, rms-flux relation, and power spectral density analysis. The spectral analysis include estimating a model independent flux hardness ratio and fitting the observations with multiplicative and additive spectral models such as \textit{power-law}, \textit{log-parabola}, \textit{broken power-law}, and \textit{black body}. The \textit{black body} represents the thermal emission from the accretion disk, while the other models represent the possible energy distributions of the particles emitting synchrotron radiation in the jet. During the past two decades, the source flux changed by of a factor of three, with a considerable fractional variability of 27\%. However, the intraday variation was found to be moderate. Flux distributions of the individual observations were consistent with a normal or log-normal distribution, while the overall flux distribution including entire observations appear to be rather multi-modal and of a complex shape. The spectral analyses indicate that \textit{log-parabola} added with a \textit{black body} gives the best fit for most of the observations. The results indicate a complex scenario in which the variability can be attributed to the intricate interaction between the disk/corona system and the jet.Comment: 18 pages, 8 figures, ApJ accepte

The representation of subordinate shape similarity in human occipitotemporal cortex

We investigated the coding of subordinate shape similarity in human object-selective cortex in two event-related functional magnetic resonance adaptation (fMR-A) experiments. Previous studies using faces have concluded that there is a narrow tuning of neuronal populations selective to each face, and that tuning is relative to the expected "average" face (norm-based encoding). Here we investigated these issues using outlines of animals and tools occupying a particular position on different morphing sequences per category. In a first experiment, we inferred the width of neural tuning to exemplars by examining whether the release from adaptation with increasing shape changes between two stimuli asymptotes. In a second experiment, we compared the response to central and extreme positions in shape space while controlling for the number of presentations of each unique stimulus to study whether the expected "average" category exemplar plays a role. The current fMR-A results show that a small change in exemplar shape produces a large release of adaptation, but only for outline shape changes of animals and not for man-made tools. Furthermore, our results suggested that central and extreme positions were not treated differently. Together, these results suggest a narrow tuning in object-selective cortex for individual exemplars from natural object categories, consistent with an exemplar-based encoding principle

Host and environmental predictors of exhaled breath temperature in the elderly

BACKGROUND: Exhaled breath temperature has been suggested as a new method to detect and monitor pathological processes in the respiratory system. The putative mechanism of this approach is based upon changes in the blood flow. So far potential factors that influence breath temperature have not been studied in the general population. METHODS: The exhaled breath temperature was measured in 151 healthy non-smoking elderly (aged: 60–80 years) at room temperature with the X-halo device with an accuracy of 0.03°C. We related exhaled breath temperature by use of regression models with potential predictors including: host factors (sex, age) and environmental factors (BMI, physical activity, and traffic indicators). RESULTS: Exhaled breath temperature was lower in women than in men and was inversely associated with age, physical activity. BMI and daily average ambient temperature were positively associated with exhaled breath temperature. Independent of the aforementioned covariates, exhaled breath temperature was significantly associated with several traffic indicators. Residential proximity to major road was inversely associated with exhaled breath temperature: doubling the distance to the nearest major intense road was observed a decrease of 0.17°C (95% CI: -0.33 to -0.01; p = 0.036). CONCLUSIONS: Exhaled breath temperature has been suggested as a noninvasive method for the evaluation of airway inflammation. We provide evidence that several factors known to be involved in proinflammatory conditions including BMI, physical activity and residential proximity to traffic affect exhaled breath temperature. In addition, we identified potential confounders that should be taken into account in clinical and epidemiological studies on exhaled breath temperature including sex, age, and ambient temperature

Double Haploidentical Hematopoietic Stem Cell Transplantation Results in Successful Engraftment of Bone Marrow from Both Donors without Graft-versus-Host or Graft-versus-Graft Effects

We established double-haploidentical (DH) hematopoietic stem cell transplantation (HSCT) murine models to explore competitive engraftment, graft-versus-graft effect and graft-versus-host disease (GVHD). T cell–depleted (TCD) bone marrow (BM) cells from B6SJF1 (donor 1 [D1]) and B6D2F1 (donor 2 [D2]) mice achieved >90% donor engraftment when transplanted into B6CBAF1 mice. B6CBAF1 recipients survived without evidence of GVHD when undergoing HSCT with TCD-BM from 2 haploidentical donors, D1 and D2. DH-HSCT recipients had significantly higher leukocyte and neutrophil counts than single-haploidentical HSCT recipients from either D1 or D2. DH recipients consistently showed successful mixed chimerism in both BM and spleen. Two other DH-HSCT models, B6D2F1 + C3D2F1→B6C3F1 and B6CBAF1 + B6SJLF1→B6D2F1, showed similar engraftment patterns. Low-dose T cell infusion from both D1 and D2 increased the degree of early engraftment of the respective donors in BM and spleen; however, this early engraftment pattern did not determine long-term engraftment dominance. In the long term, minimally engrafted D1 BM recovered and comprised >50% of all donor- derived B, T, and natural killer cells. We conclude that early BM engraftment is determined by donor T cell immunodominance, but long-term engraftment is related to the engraftment potential of stem cells after DH-HSCT

Recent JET Experiments on Alfvén Eigenmodes with Intermediate Toroidal Mode Numbers: Measurements and Modelling with the TAEFL code

This paper reports the results of recent experiments performed on the JET tokamak on Alfven eigenmodes (AEs) with toroidal mode number (n) in the range n=3—15. The stability properties of these medium-n AEs are investigated experimentally using a new set of compact in-vessel antennas, providing a direct and real-time measurement of the frequency, damping rate and amplitude for each individual toroidal mode number. We report here the quantitative analysis of the measurements of the damping rate for stable n=3 toroidal AEs as a function of the edge plasma elongation, and the theoretical analysis of these data with the TAEFL code. The TAEFL results are in excellent qualitative agreement with the measurements, reproducing well the experimental scaling of increasing damping rate versus increasing edge elongation, and in many cases are also quantitatively correct, with a difference with respect to the measurements below 30%, particularly for magnetic configurations that have a larger edge magnetic shear

Measurement of the Damping Rate of High-n Toroidal Alfven Eigenmodes in JET

A new set of compact in-vessel antennas has been built and installed in JET to provide for the first time the direct measurement of the damping rate (/) of stable Alfvén Eigenmodes (AEs) with toroidal mode number (n) in the range n=3-15. This paper reports the first quantitative analysis of the measurements of the damping rate for these modes as function of the edge plasma elongation (95). We find that the scaling of / vs. 95 for medium-n Toroidal AEs, with n=3-7, follows the same trend previously measured and explained theoretically for the n=1 and n=2 modes. This confirms the possibility of using the edge shape parameters as a real-time actuator for control of the stability of alpha-particles driven AEs in burning plasma experiments, such as ITER