Dosimetric impact of gastrointestinal air column in radiation treatment of pancreatic cancer

OBJECTIVE: Dosimetric evaluation of air column in gastrointestinal (GI) structures in intensity modulated radiation therapy (IMRT) of pancreatic cancer. METHODS: Nine sequential patients were retrospectively chosen for dosimetric analysis of air column in the GI apparatus in pancreatic cancer using cone beam CT (CBCT). The four-dimensional CT (4DCT) was used for target and organs at risk (OARs) and non-coplanar IMRT was used for treatment. Once a week, these patients underwent CBCT for air filling, isocentre verification and dose calculations retrospectively. RESULTS: Abdominal air column variation was as great as ±80% between weekly CBCT and 4DCT. Even with such a large air column in the treatment path for pancreatic cancer, changes in anteroposterior dimension were minimal (2.8%). Using IMRT, variations in air column did not correlate dosimetrically with large changes in target volume. An average dosimetric deviation of mere -3.3% and a maximum of -5.5% was observed. CONCLUSION: CBCT revealed large air column in GI structures; however, its impact is minimal for target coverage. Because of the inherent advantage of segmentation in IMRT, where only a small fraction of a given beam passes through the air column, this technique might have an advantage over 3DCRT in treating upper GI malignancies where the daily air column can have significant impact. Advances in knowledge: Radiation treatment of pancreatic cancer has significant challenges due to positioning, imaging of soft tissues and variability of air column in bowels. The dosimetric impact of variable air column is retrospectively studied using CBCT. Even though, the volume of air column changes by ± 80%, its dosimetric impact in IMRT is minimum

Heterosis and Composition of Sweet Sorghum

Sweet sorghum (Sorghum bicolor) has potential as a bioenergy feedstock due to its high yield potential and the production of simple sugars for fermentation. Sweet sorghum cultivars are typically tall, high biomass types with juicy stalks and high sugar concentration. These sorghums can be harvested, milled, and fermented to ethanol using technology similar to that used to process sugarcane. Sweet sorghum has advantages in that it can be planted by seed with traditional planters, is an annual plant that quickly produces a crop and fits well in crop rotations, and it is a very water-use efficient crop. Processing sweet sorghum is capital intensive, but it could fit into areas where sugarcane is already produced. Sweet sorghum could be timed to harvest and supply the sugar mill during the off season when sugarcane is not being processed, be fit into crop rotations, or used in water limiting environments. In these ways, sweet sorghum could be used to produce ethanol in the Southern U.S and other tropical and subtropical environments. Traditionally, sweet sorghum has been grown as a pureline cultivar. However, these cultivars produce low quantities of seed and are often too tall for efficient mechanical harvest. Sweet sorghum hybrids that use grain-type seed parents with high sugar concentrations are one way to overcome limitation to seed supply and to capture the benefits of heterosis. There are four objectives of this research. First to evaluate the importance of genotype, environment, and genotype-by-environment interaction effects on the sweet sorghum yield and composition. The second objective is to determine the presence and magnitude of heterosis effects for traits related to sugar production in sweet sorghum. Next: to study the ability of sweet sorghum hybrids and cultivars to produce a ratoon crop and determine the contribution of ratoon crops to total sugar yield. The final objective is to evaluate variation in composition of sweet sorghum juice and biomass. Sweet sorghum hybrids, grain-type sweet seed parents, and traditional cultivars that served as male parents were evaluated in multi-environment trials in Weslaco, College Station, and Halfway, Texas in 2007 and 2008. Both genotype and environment influenced performance, but environment had a greater effect than genotype on the composition of sweet sorghum juice and biomass yield. In comparing performance, elite hybrids produced fresh biomass and sugar yields similar to the traditional cultivars while overcoming the seed production limitations. High parent heterosis was expressed among the experimental hybrids for biomass yield, sugar yield and sugar concentration. Additional selection for combining ability would further enhance yields and heterosis in the same hybrid. Little variation was observed among hybrids for juice and biomass composition suggesting that breeding efforts should focus on yield before altering plant composition

Characterizing Single Polymeric and Protein Nanoparticles with Surface Plasmon Resonance Imaging Measurements

Near-infrared surface plasmon resonance imaging (SPRI) microscopy is used to detect and characterize the adsorption of single polymeric and protein nanoparticles (PPNPs) onto chemically modified gold thin films in real time. The single-nanoparticle SPRI responses, Δ%R_(NP), from several hundred adsorbed nanoparticles are collected in a single SPRI adsorption measurement. Analysis of Δ%R_(NP) frequency distribution histograms is used to provide information on the size, material content, and interparticle interactions of the PPNPs. Examples include the measurement of log-normal Δ%R_(NP) distributions for mixtures of polystyrene nanoparticles, the quantitation of bioaffinity uptake into and aggregation of porous NIPAm-based (N-isopropylacrylamide) hydrogel nanoparticles specifically engineered to bind peptides and proteins, and the characterization of the negative single-nanoparticle SPRI response and log-normal Δ%R_(NP) distributions obtained for three different types of genetically encoded gas-filled protein nanostructures derived from bacteria

SLC19A1 transports immunoreactive cyclic dinucleotides.

The accumulation of DNA in the cytosol serves as a key immunostimulatory signal associated with infections, cancer and genomic damage1,2. Cytosolic DNA triggers immune responses by activating the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway3. The binding of DNA to cGAS activates its enzymatic activity, leading to the synthesis of a second messenger, cyclic guanosine monophosphate-adenosine monophosphate (2'3'-cGAMP)4-7. This cyclic dinucleotide (CDN) activates STING8, which in turn activates the transcription factors interferon regulatory factor 3 (IRF3) and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), promoting the transcription of genes encoding type I interferons and other cytokines and mediators that stimulate a broader immune response. Exogenous 2'3'-cGAMP produced by malignant cells9 and other CDNs, including those produced by bacteria10-12 and synthetic CDNs used in cancer immunotherapy13,14, must traverse the cell membrane to activate STING in target cells. How these charged CDNs pass through the lipid bilayer is unknown. Here we used a genome-wide CRISPR-interference screen to identify the reduced folate carrier SLC19A1, a folate-organic phosphate antiporter, as the major transporter of CDNs. Depleting SLC19A1 in human cells inhibits CDN uptake and functional responses, and overexpressing SLC19A1 increases both uptake and functional responses. In human cell lines and primary cells ex vivo, CDN uptake is inhibited by folates as well as two medications approved for treatment of inflammatory diseases, sulfasalazine and the antifolate methotrexate. The identification of SLC19A1 as the major transporter of CDNs into cells has implications for the immunotherapeutic treatment of cancer13, host responsiveness to CDN-producing pathogenic microorganisms11 and-potentially-for some inflammatory diseases

Roles of T follicular helper cells and T follicular regulatory cells in Autoantibody Production in IL-2-deficient mice

Autoantibodies can result from excessive T follicular helper (Tfh) cell activity, whereas T follicular regulatory (Tfr) cells negatively regulate autoantibody production. IL-2 knockout (KO) mice on the BALB/c background have elevated Tfh responses, produce autoantibodies, and develop lethal autoimmunity. We analyzed Tfh and Tfr cells in IL-2 KO mice on the C57BL/6 (B6) genetic background. In B6 IL-2 KO mice, the spontaneous formation of Tfh cells and germinal center B cells was greatly enhanced, along with production of anti-DNA autoantibodies. IL-2 has been reported to repress Tfr cell differentiation; however, Tfr cells were not increased over wild-type levels in the B6 IL-2 KO mice. To assess Tfh and Tfr cell regulation of autoantibody production in IL-2 KO mice, we generated IL-2 KO mice with a T cell-specific deletion of the master Tfh cell transcription factor Bcl6. In IL-2 KO Bcl6 conditional KO (2KO-Bcl6TC) mice, Tfh cells, Tfr cells, and germinal center B cells were ablated. In contrast to expectations, autoantibody IgG titers in 2KO-Bcl6TC mice were significantly elevated over autoantibody IgG titers in IL-2 KO mice. Specific deletion of Tfr cells with Foxp3-cre Bcl6-flox alleles in IL-2 KO mice led to early lethality, before high levels of autoantibodies could develop. We found IL-2+/+ Tfr cell-deficient mice produce significant levels of autoantibodies. Our overall findings provide evidence that Tfh cells are dispensable for high-level production of autoantibodies and also reveal a complex interplay between Tfh and Tfr cells in autoantibody production and autoimmune disease