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A study was conducted to investigate the effects of apple juice concentrate and blackcurrant concentrate (BCC) syrup mixture level, osmotic soaking time and drying temperature on the drying characteristics and ascorbic acid content of the dried product using the response surface methodology, as well as to determine the optimized conditions for hot air drying of the blackcurrant-infused apple cubes. The drying of blackcurrant-infused apple cubes consist of only one falling rate period (FRP) with no constant rate period. The critical moisture content of infused apple cubes increased with decreasing soaking time, the FRP drying coefficient increased with temperature, the equilibrium moisture content decreased with increasing temperature and decreasing soaking time and the ascorbic acid content increased with BCC level and soaking time. The optimized conditions for hot air drying of the blackcurrant-infused apple cubes were derived. [ABSTRACT FROM AUTHOR]

A comprehensive collection of full-length cDNAs is essential for correct structural gene annotation and functional analyses of genes. We constructed a mixed full-length cDNA library from 21 different tissues of Brachypodium distachyon Bd21, and obtained 78,163 high quality expressed sequence tags (ESTs) from both ends of ca. 40,000 clones (including 16,079 contigs). We updated gene structure annotations of Brachypodium genes based on full-length cDNA sequences in comparison with the latest publicly available annotations. About 10,000 non-redundant gene models were supported by full-length cDNAs; ca. 6,000 showed some transcription unit modifications. We also found ca. 580 novel gene models, including 362 newly identified in Bd21. Using the updated transcription start sites, we searched a total of 580 plant cis-motifs in the −3 kb promoter regions and determined a genome-wide Brachypodium promoter architecture. Furthermore, we integrated the Brachypodium full-length cDNAs and updated gene structures with available sequence resources in wheat and barley in a web-accessible database, the RIKEN Brachypodium FL cDNA database. The database represents a “one-stop” information resource for all genomic information in the Pooideae, facilitating functional analysis of genes in this model grass plant and seamless knowledge transfer to the Triticeae crops. [ABSTRACT FROM AUTHOR]

Loss-of-function mutations in ABCC6 can cause chronic or acute forms of dystrophic mineralization described in disease models such as pseudoxanthoma elasticum (OMIM 26480) in human and dystrophic cardiac calcification in mice. The ABCC6 protein is a large membrane-embedded organic anion transporter primarily found in the plasma membrane of hepatocytes. We have established a complex experimental strategy to determine the structural and functional consequences of diseasecausing mutations in the human ABCC6. The major aim of our study was to identify mutants with preserved transport activity but failure in intracellular targeting. Five missense mutations were investigated: R1138Q, V1298F, R1314W, G1321S and R1339C. Using in vitro assays, we have identified two variants; R1138Q and R1314W that retained significant transport activity. All mutants were transiently expressed in vivo, in mouse liver via hydrodynamic tail vein injections. The inactive V1298F was the only mutant that showed normal cellular localization in liver hepatocytes while the other mutants showed mostly intracellular accumulation indicating abnormal trafficking. As both R1138Q and R1314W displayed endoplasmic reticulum localization, we tested whether 4-phenylbutyrate (4-PBA), a drug approved for clinical use, could restore their intracellular trafficking to the plasma membrane in MDCKII and mouse liver. The cellular localization of R1314W was significantly improved by 4-PBA treatment, thus potentially rescuing its physiological function. Our work demonstrates the feasibility of the in vivo rescue of cellular maturation of some ABCC6 mutants in physiological conditions very similar to the biology of the fully differentiated human liver and could have future human therapeutic application. [ABSTRACT FROM AUTHOR]

This paper presents a speech synthesis system using the neural network. While there have been a large number of speech synthesis systems developed, most of them are rule-based systems for a restricted [ABSTRACT FROM AUTHOR]

Advancing chimeric antigen receptor (CAR)-engineered adoptive T cells for the treatment of solid cancers is a major focus in the field of immunotherapy, given impressive recent clinical responses in hematological malignancies. Prostate cancer may be amenable to T cell-based immunotherapy since several tumor antigens, including prostate stem-cell antigen (PSCA), are widely over-expressed in metastatic disease. While antigen selectivity of CARs for solid cancers is crucial, it is problematic due to the absence of truly restricted tumor antigen expression and potential safety concerns with “on-target off-tumor” activity. Here, we show that the intracellular co-stimulatory signaling domain can determine a CAR's sensitivity for tumor antigen expression. A 4-1BB intracellular co-stimulatory signaling domain in PSCA-CARs confers improved selectivity for higher tumor antigen density, reduced T cell exhaustion phenotype, and equivalent tumor killing ability compared to PSCA-CARs containing the CD28 co-stimulatory signaling domain. PSCA-CARs exhibit robustin vivoanti-tumor activity in patient-derived bone-metastatic prostate cancer xenograft models, and 4-1BB-containing CARs show superior T cell persistence and control of disease compared with CD28-containing CARs. Our study demonstrates the importance of co-stimulation in defining an optimal CAR T cell, and also highlights the significance of clinically relevant models in developing solid cancer CAR T cell therapies. [ABSTRACT FROM AUTHOR]

Purpose: The usage of radioactive Technetium99m (Tc99m) colloid for the purpose of sentinel lymph node biopsy (SLNB) in early breast cancer is considered the gold standard in Germany. However, new tracers, such as near-infrared (NIR) imaging agents like indocyanine green (ICG) could offer an alternative in future, as they overcome drawbacks associated with radioactive Technetium99m (Tc99m) like limited availability, high costs and radioactivity exposure for both patients and surgeons. Methods: In this double-arm retrospective study, we sought to establish the usefulness of indocyanine green as an alternative or an addition to the conventional Technetium99m (Tc99m) in the identification of the SLN in early breast cancer. Results: Among the 161 patients who underwent primary SLNB, 34 patients had at least 1 SLN with metastasis. Among these patients with SLN metastasis, 33 had the SLN detected by ICG; while 31 had the SLN detected by Tc99m. The conventional Technetium99m radiotracer failed to detect 2 patients with metastasis in this Arm of the study. Among the 87 patients who underwent SLNB after NACT, 13 patients had at least 1 SLN with metastasis. Among these 13 patients with SLN metastasis, ICG and Tc99m had detected the SLN among 12 patients, while 1 patient had been detected by ICG alone. Conclusions: Our results show that ICG is as effective as the radioisotope for SLNB even among patients who have undergone NACT. This trial is registered with the German Clinical Trial Register, ID: DRKS00013606. [ABSTRACT FROM AUTHOR]

Objective: Purpose of our study is to assess the relationship between MRI findings and invasive breast cancer (IBC) with cancer-associated fibroblasts (CAFs) that are positive for podoplanin. Methods: We retrospectively analyzed the consecutive 109 IBCs. The IBCs were dichotomized as with (+) or without (−) podoplanin-positive CAFs. In MRI analyses, the dichotomized IBCs were compared the lesion to muscle ratio (L/M ratio) in STIR images, the ADC value, the distribution of kinetic parameters, and morphological findings. Results: Of the 109 IBCs, 28 (26%) IBCs had podoplanin(+) CAFs. Compared to the podoplanin(−) group, the podoplanin(+) group tended to have a more malignant pathological status. In the STIR images, the podoplanin(+) group had significantly higher L/M ratio (7.59 vs. 6.55, p = 0.040). In a dynamic study, the podoplanin(+) group had a significantly higher percentage of the washout pattern (42.21% vs. 29.43%, p = 0.045). There were 23 mass lesions and 5 non-mass enhancement (NME) lesions in the podoplanin(+) group, and 69 mass lesions and 12 NME lesions in the podoplanin(−) group. The mass lesions of the podoplanin(−) group had a significantly higher likelihood of showing an irregular shape (n = 47 vs. 8, p = 0.035). The podoplanin(+) group's lesions had a significantly higher likelihood of showing a circumscribed margin (n = 14 vs. 6, p < 0.001) and a rim enhancement (n = 10 vs. 13, p = 0.047). In multivariate analyses, only high nuclear grade was significant predictive value of podoplanin(+) CAFs. Conclusion: Although not significant in multivariate analyses, MRI findings may be used to determine the podoplanin-positive CAF status of invasive breast cancer. [ABSTRACT FROM AUTHOR]

The first study reporting the morphological characterization of Sarcocystis sybillensis was performed in 1983; however, without any molecular analysis. Sarcocystis nipponi has been recently described as a species synonymic to S. sybillensis. We reconfirmed the presence of S. sybillensis in Japanese sika deer (Cervus nippon) captured in its native territory; and performed its molecular and phylogenetic characterization. The morphological characteristics of the sarcocysts were consistent with those of S. nipponi and S. sybillensis described in the first report. However, the nucleotide sequence of 18S rRNA gene of S. sybillensis showed only 91.9% identity to that of S. nipponi, suggesting low homology among the concerned Sarcocystis spp. Accordingly, S. sybillensis was found to occupy a clade distinct from that of S. nipponi in a phylogenetic tree of Sarcocystis. Therefore, the present study provides essential information on 18S rRNA-based molecular characterization of S. sybillensis and disproves the existing notion of morphology-based species synonymity of S. sibillensis and S. nipponi. These results also suggest that S. sybillensis belongs to type 2 Sarcocystis. [ABSTRACT FROM AUTHOR]