Local endothelial complement activation reverses endothelial quiescence, enabling t-cell homing, and tumor control during t-cell immunotherapy.

Cancer immunotherapy relies upon the ability of T cells to infiltrate tumors. The endothelium constitutes a barrier between the tumor and effector T cells, and the ability to manipulate local vascular permeability could be translated into effective immunotherapy. Here, we show that in the context of adoptive T cell therapy, antitumor T cells, delivered at high enough doses, can overcome the endothelial barrier and infiltrate tumors, a process that requires local production of C3, complement activation on tumor endothelium and release of C5a. C5a, in turn, acts on endothelial cells promoting the upregulation of adhesion molecules and T-cell homing. Genetic deletion of C3 or the C5a receptor 1 (C5aR1), and pharmacological blockade of C5aR1, impaired the ability of T cells to overcome the endothelial barrier, infiltrate tumors, and control tumor progression in vivo, while genetic chimera mice demonstrated that C3 and C5aR1 expression by tumor stroma, and not leukocytes, governs T cell homing, acting on the local endothelium. In vitro, endothelial C3 and C5a expressions were required for endothelial activation by type 1 cytokines. Our data indicate that effective immunotherapy is a consequence of successful homing of T cells in response to local complement activation, which disrupts the tumor endothelial barrier

Mononuclear phagocyte system function and nanoparticle pharmacology in obese and normal weight ovarian and endometrial cancer patients

Purpose: Obesity may alter mononuclear phagocyte system (MPS) function and the pharmacology and efficacy of nanoparticles therapies, such as PEGylated liposomal doxorubicin (PLD). We aimed to evaluate the relationships between hormone and chemokine mediators of MPS function and the pharmacokinetic (PK) exposure of PLD in obese and normal weight patients with ovarian and endometrial cancer. Methods: Hormone and chemokine mediators in obese and normal weight ovarian and endometrial cancer patients were measured. A separate pharmacology study was performed that evaluated the relationship between serum hormone concentrations, MPS function, and PK disposition of PLD in refractory ovarian cancer patients. Results: Univariate analysis revealed a significant relationship between serum estradiol and body mass index (OR 8.64, 95% CI 2.67–28.0, p < 0.001). Estrone and testosterone concentrations were positively correlated with MPS function (ρ = 0.57 and 0.53, p = 0.14 and 0.18, respectively) and inversely correlated with PLD PK exposure (ρ = − 0.75 and − 0.76, respectively, p = 0.02 for both). Conclusions: Higher MPS function resulting in reduced PLD exposure is a potential mechanism for reduced efficacy of PLD and other nanoparticles observed in obese patients with cancer. PK simulations suggest higher doses of PLD are required in obese patients to achieve similar exposures as standard dosing in normal weight patients

Iron-modified biochar and water management regime-induced changes in plant growth, enzyme activities, and phytoavailability of arsenic, cadmium and lead in a paddy soil

The aim of this study was to evaluate the effect of raw (RawBC) and iron (Fe)-modified biochar (FeBC) derived from Platanus orientalis Linn branches on the plant growth, enzyme activity, and bioavailability and uptake of As, Cd, and Pb by rice in a paddy soil with continuously flooded (CF) or alternately wet and dry (AWD) irrigation in a pot experiment. Application of RawBC (3%, w/w) significantly increased soil pH, while FeBC decreased it. The FeBC was more effective in reducing As and Pb bioavailability, particularly under the AWD water regime, while RawBC was more conducive in reducing Cd bioavailability under the CF water regime. The FeBC decreased As concentration, but increased concentrations of Cd and Pb in the straw and brown rice, as compared to the untreated soil. Soil catalase and urease activities were enhanced by RawBC, but decreased by FeBC treatment. The FeBC increased the grain yield by 60 and 32% in CF and AWD treatments, respectively. The FeBC can be recommended for immobilization of As in paddy soils, but a potential human health risk from Cd and Pb in FeBC-treated soils should be considered due to increased uptake and translocation of the metals to brown rice

Atmospheric Heating and Wind Acceleration: Results for Cool Evolved Stars based on Proposed Processes

A chromosphere is a universal attribute of stars of spectral type later than ~F5. Evolved (K and M) giants and supergiants (including the zeta Aurigae binaries) show extended and highly turbulent chromospheres, which develop into slow massive winds. The associated continuous mass loss has a significant impact on stellar evolution, and thence on the chemical evolution of galaxies. Yet despite the fundamental importance of those winds in astrophysics, the question of their origin(s) remains unsolved. What sources heat a chromosphere? What is the role of the chromosphere in the formation of stellar winds? This chapter provides a review of the observational requirements and theoretical approaches for modeling chromospheric heating and the acceleration of winds in single cool, evolved stars and in eclipsing binary stars, including physical models that have recently been proposed. It describes the successes that have been achieved so far by invoking acoustic and MHD waves to provide a physical description of plasma heating and wind acceleration, and discusses the challenges that still remain.Comment: 46 pages, 9 figures, 1 table; modified and unedited manuscript; accepted version to appear in: Giants of Eclipse, eds. E. Griffin and T. Ake (Berlin: Springer

pi Conjugated small molecules enable efficient perovskite growth and charge extraction for high performance photovoltaic devices

A amp; 960; conjugated small molecule N,N amp; 8242; bis naphthalen 1 yl N,N bis phenyl benzidine NPB is introduced into a poly bis 4 phenyl 2,4,6 trimethylphenyl amine PTAA hole transport layer in inverted perovskite solar cells PSCs . The NPB doping induces better perovskite crystal growth owing to a strong amp; 960; amp; 960; interaction with PTAA and cation amp; 960; interactions with CH3NH3 MA . In addition, NPB doping not only improves the wettability of PTAA and regulates the perovskite crystallization to achieve a larger grain size, but also moves the valence band energy of the hole transport layer closer to the perovskite layer. Consequently, the fabricated PSCs delivered a power conversion efficiency PCE of 20.15 , with a short circuit current density JSC of 22.60 amp; 8239;mA cm2 and open circuit voltage VOC of 1.14 amp; 8239;V. This outcome indicates that PTAA NPB composite materials present great potential for fabricating high performance PSC

Healthy lifestyle and life expectancy free of cancer, cardiovascular disease, and type 2 diabetes: prospective cohort study

OBJECTIVE: To examine how a healthy lifestyle is related to life expectancy that is free from major chronic diseases. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: The Nurses' Health Study (1980-2014; n=73 196) and the Health Professionals Follow-Up Study (1986-2014; n=38 366). MAIN EXPOSURES: Five low risk lifestyle factors: never smoking, body mass index 18.5-24.9, moderate to vigorous physical activity (≥30 minutes/day), moderate alcohol intake (women: 5-15 g/day; men 5-30 g/day), and a higher diet quality score (upper 40%). MAIN OUTCOME: Life expectancy free of diabetes, cardiovascular diseases, and cancer. RESULTS: The life expectancy free of diabetes, cardiovascular diseases, and cancer at age 50 was 23.7 years (95% confidence interval 22.6 to 24.7) for women who adopted no low risk lifestyle factors, in contrast to 34.4 years (33.1 to 35.5) for women who adopted four or five low risk factors. At age 50, the life expectancy free of any of these chronic diseases was 23.5 (22.3 to 24.7) years among men who adopted no low risk lifestyle factors and 31.1 (29.5 to 32.5) years in men who adopted four or five low risk lifestyle factors. For current male smokers who smoked heavily (≥15 cigarettes/day) or obese men and women (body mass index ≥30), their disease-free life expectancies accounted for the lowest proportion (≤75%) of total life expectancy at age 50. CONCLUSION: Adherence to a healthy lifestyle at mid-life is associated with a longer life expectancy free of major chronic diseases

Probing exotic phenomena at the interface of nuclear and particle physics with the electric dipole moments of diamagnetic atoms: A unique window to hadronic and semi-leptonic CP violation

The current status of electric dipole moments of diamagnetic atoms which involves the synergy between atomic experiments and three different theoretical areas -- particle, nuclear and atomic is reviewed. Various models of particle physics that predict CP violation, which is necessary for the existence of such electric dipole moments, are presented. These include the standard model of particle physics and various extensions of it. Effective hadron level combined charge conjugation (C) and parity (P) symmetry violating interactions are derived taking into consideration different ways in which a nucleon interacts with other nucleons as well as with electrons. Nuclear structure calculations of the CP-odd nuclear Schiff moment are discussed using the shell model and other theoretical approaches. Results of the calculations of atomic electric dipole moments due to the interaction of the nuclear Schiff moment with the electrons and the P and time-reversal (T) symmetry violating tensor-pseudotensor electron-nucleus are elucidated using different relativistic many-body theories. The principles of the measurement of the electric dipole moments of diamagnetic atoms are outlined. Upper limits for the nuclear Schiff moment and tensor-pseudotensor coupling constant are obtained combining the results of atomic experiments and relativistic many-body theories. The coefficients for the different sources of CP violation have been estimated at the elementary particle level for all the diamagnetic atoms of current experimental interest and their implications for physics beyond the standard model is discussed. Possible improvements of the current results of the measurements as well as quantum chromodynamics, nuclear and atomic calculations are suggested.Comment: 46 pages, 19 tables and 16 figures. A review article accepted for EPJ

Dairy intake during adolescence and risk of colorectal adenoma later in life

BACKGROUND: Higher dairy intake during adulthood has been associated with lower colorectal cancer risk. As colorectal carcinogenesis spans several decades, we hypothesised that higher dairy intake during adolescence is associated with lower risk of colorectal adenoma, a colorectal cancer precursor. METHODS: In 27,196 females from the Nurses’ Health Study 2, aged 25–42 years at recruitment (1989), who had completed a validated high school diet questionnaire in 1998 and undergone at least one lower bowel endoscopy between 1998 and 2011, logistic regression for clustered data was used to calculate odds ratios (ORs) and 95% confidence intervals (CI). RESULTS: Colorectal adenomas were diagnosed in 2239 women. Dairy consumption during adolescence was not associated with colorectal adenoma risk (OR highest vs. lowest [≥4 vs. ≤1.42 servings/day] quintile [95% CI] 0.94 [0.80, 1.11]). By anatomical site, higher adolescent dairy intake was associated with lower rectal (0.63 [0.42, 0.95]), but not proximal (1.01 [0.80, 1.28]) or distal (0.97 [0.76, 1.24]) colon adenoma risk. An inverse association was observed with histologically advanced (0.72 [0.51, 1.00]) but not non-advanced (1.07 [0.86, 1.33]) adenoma. CONCLUSIONS: In this large cohort of younger women, higher adolescent dairy intake was associated with lower rectal and advanced adenoma risk later in life

Shrinking a large dataset to identify variables associated with increased risk of Plasmodium falciparum infection in Western Kenya

Large datasets are often not amenable to analysis using traditional single-step approaches. Here, our general objective was to apply imputation techniques, principal component analysis (PCA), elastic net and generalized linear models to a large dataset in a systematic approach to extract the most meaningful predictors for a health outcome. We extracted predictors for Plasmodium falciparum infection, from a large covariate dataset while facing limited numbers of observations, using data from the People, Animals, and their Zoonoses (PAZ) project to demonstrate these techniques: data collected from 415 homesteads in western Kenya, contained over 1500 variables that describe the health, environment, and social factors of the humans, livestock, and the homesteads in which they reside. The wide, sparse dataset was simplified to 42 predictors of P. falciparum malaria infection and wealth rankings were produced for all homesteads. The 42 predictors make biological sense and are supported by previous studies. This systematic data-mining approach we used would make many large datasets more manageable and informative for decision-making processes and health policy prioritization

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012