The catch connective, or mutable collagenous, tissue of echinoderms changes its mechanical properties in response to stimulation. The body wall dermis of sea cucumbers is a typical catch connective ...tissue. The dermis assumes three mechanical states: soft, standard, and stiff. Proteins that change the mechanical properties have been purified from the dermis. Tensilin and the novel stiffening factor are involved in the soft to standard and standard to stiff transitions, respectively. Softenin softens the dermis in the standard state. Tensilin and softenin work directly on the extracellular matrix (ECM). This review summarizes the current knowledge regarding such stiffeners and softeners. Attention is also given to the genes of tensilin and its related proteins in echinoderms. In addition, we provide information on the morphological changes of the ECM associated with the stiffness change of the dermis. Ultrastructural study suggests that tensilin induces an increase in the cohesive forces with the lateral fusion of collagen subfibrils in the soft to standard transition, that crossbridge formation between fibrils occurs in both the soft to standard and standard to stiff transitions, and that the bond which accompanies water exudation produces the stiff dermis from the standard state.
Many clinical trials of peptide vaccines have been carried out since the first clinical trial of a melanoma antigen gene‐1‐derived peptide‐based vaccine was reported in 1995. The earlier generations ...of peptide vaccines were composed of one to several human leukocyte antigen class I‐restricted CTL‐epitope peptides of a single human leukocyte antigen type. Currently, various types of next‐generation peptide vaccines are under development. In this review, we focus on the clinical trials of the following categories of peptide vaccines mainly published from 2008 to 2012: (i) multivalent long peptide vaccines; (ii) multi‐peptide vaccines consisting of CTL‐ and helper‐epitopes; (iii) peptide cocktail vaccines; (iv) hybrid peptide vaccines; (v) personalized peptide vaccines; and (vi) peptide‐pulsed dendritic cell vaccines. (Cancer Sci 2013; 104: 15–21)
Accumulated clinical data of immune checkpoint blockades have suggested the importance of neoantigens in cancer immunity. Tumor antigens are released from dead cancer cells together with cellular ...components, such as damage‐associated molecular patterns (DAMPs), into the tumor microenvironment. We recently reported that high mobility group box 1 (HMGB1), a representative DAMP molecule, showed a negative impact on anti‐tumor immunity. However, a positive role of HMGB1 in the initiation of innate and subsequent adaptive immunity has also been demonstrated; thus, the effects of HMGB1 on anti‐tumor immunity have not been well understood. In this study, we identified nine immunogenic neoantigen epitopes of B16F10 murine melanoma cells and subsequently investigated the effects of suppression of HMGB1 on the induction of neoantigen‐specific immunity using HMGB1‐knockout tumors. Neoantigen‐reactive T cells were expanded in B16F10 tumor‐bearing mice, and T cell receptor repertoire analysis suggested that neoantigen‐reactive T cells were oligo‐clonally increased in B16F10 tumor bearers. An increase of neoantigen‐reactive T cells and oligoclonal expansion of the T cells were similarly detected in HMGB1‐knockout tumor‐bearing mice. The induction of neoantigen‐specific immunity under the suppression of HMGB1 in the tumor microenvironment shown in this study supports further development of combination therapy of HMGB1 suppression with neoantigen‐targeted cancer immunotherapies, including immune checkpoint blockade therapy.
We recently reported that HMGB1 showed a negative impact on anti‐tumor immunity, however, a positive role of HMGB1 in the initiation of innate and subsequent adaptive immunity has also been shown. In this study, we found that the suppression of HMGB1 in the tumor microenvironment does not inhibit the induction of neoantigen‐specific immunity.
As an application of the theory of reproducing kernel Hilbert spaces we prove a theorem on the existence of bounded solutions of a system of linear operator equations in Hilbert spaces. This result ...is obtained by using locally convex spaces and is a corollary to an extension of the well-known Parrott’s theorem. Our theorems extend the Strong Parrott Theorem and its extensions. Our tools for the proof are the generalized reproducing kernel Hilbert spaces due to Schwartz, and the complementary spaces due to de Branges and Rovnyak.
Therapeutic cancer vaccines have enjoyed little success so far, although many clinical trials have been conducted. Therefore, the creation of new protocols capable of inducing an objective response ...is required. We examined two of these protocols in the present review. The first is a personalized protocol to take into account the immunological diversity of cytotoxic T lymphocyte responses among patients. The second is a combination therapy designed to adapt to the presence of major histocompatibility complex (MHC)‐loss cancer cells. The objective response rates of our classical (non‐personalized) peptide vaccines were 0%, whereas that of personalized vaccines was 11.1% in the total advanced cancers and ≥20% in malignant glioma and cervical cancers, respectively. A ≥50% decrease in serum prostate‐specific antigen (PSA) was seen in 8.7% of advanced hormone refractory prostate cancer patients by personalized vaccination alone, whereas such a decrease was seen in 54% of patients when the personalized vaccination was combined with a low dose of estramustine. Based on these experiences, we propose a personalized peptide vaccine combined with chemotherapy as a new treatment modality for cancers. (Cancer Sci 2006; 97: 970–976)
Cu‐deficient layer (CDL) on Cu(In,Ga)Se2 (CIGS) promotes Cd diffusion from CdS buffer layer and forms a valence band offset (ΔEV) between CDL and CIGS. We quantitively demonstrate the effects of CDL ...formation on the performance of CIGS solar cells through experiments and theoretical simulation. To investigate the effects of Cd diffusion and ΔEV by CDL, theoretical analysis was carried out for a CIGS solar cell with a surface layer which simulated the CDL at CdS/CIGS interface. It was revealed that when electron concentration in n‐type surface layer is higher than the absolute carrier concentration in CIGS absorber (ND > |NA, CIGS|), open‐circuit voltage and fill factor are improved. Additionally, ΔEV ≥ 0.15 eV leads to the highest open‐circuit voltage by suppression of interfacial recombination. Transmission electron microscope energy dispersive X‐ray spectrometry and scanning spreading resistance microscopy were employed for the same cross section of a CIGS solar cell fabricated by three‐stage process. Despite CDL with Cu/(Ga + In) of 0.31 formed on the surface had high Cd contents of 3.4 at%, its carrier concentration of 4.8 × 1010 cm−3 was lower than that of 1014 –1016 cm−3 in grain interior owing to insufficient activation of Cd atoms. These results indicate the effectiveness of ΔEV formation by introducing CDL with low Cu/(Ga + In) of 0.31 to boost CIGS solar cell performance and difficulty in realizing ND > |NA, CIGS| by surface Cd doping.
The possibilities to improve the efficiency of Cu(In,Ga)Se2 (CIGS) solar cells by introducing a Cu‐deficient layer (CDL) at the CdS/CIGS interface were demonstrated through evaluation of CIGS and Cu(In,Ga)3Se5 single films, device simulation, and comprehensive evaluation of an 18.5% efficient CIGS solar cell. It was found that CDL leads to the formation of valence band offset and promotion of Cd‐diffusion, most importantly discovered the effectiveness of valence band offset formation and difficulty of Cd‐diffusion for enhancement of device performance.
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