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The aim of this research was to determine the minimal requirements for shear reinforcement for reactive powder concrete (RPC) rectangular cross-sectional beams with a compressive strength of 157 MPa and a steel fiber volume content of 2.0% that remained constant for all the tested beams. Additionally, the recommendations of KCI-2012 and AFGC-2013 for the design of RPC beams as well as the shear design requirements of ACI 314-2014 when applied to RPC beams were studied. Utilizing a three-dimensional finite element program, a computational model was designed for forecasting the deformations and shear strength of the examined RPC beams. Both the shear-span-to-depth relationship (a/d) and the minimal reinforcement web ratio, represented by the distance between stirrups and the diameter of the stirrup bars, are the key study parameters in this regard. According to this study's experimental findings, increasing the given reinforcement of the web ratio has little influence on both the ultimate shear strength as well as the diagonal cracking strength of the beams. Additionally, the findings demonstrated that the ACI 318-2014 maximum stirrup spacing requirement of 0.5 d can safely be extended to 0.75 d for beams that are relatively short. Compared to what ACI 318-2014 mandates, the suggestions of AFGC-2013 and KCI-2012 are more cautious and safe. According to the AFGC-2013 criteria, the mean proportion of Vfb to projected Vu,AFGC is roughly 58.3%, whereas the mean proportion of vs. and Vc is just 41.7%. The deformation response and ultimate shear strength of the examined RPC beams were well predicted by the designed model using finite elements when metal fibers were taken into account. [ABSTRACT FROM AUTHOR]

Vaccines consisting of synthetic peptides representing cytotoxic T-lymphocyte (CTL) epitopes have long been considered as a simple and cost-effective approach to treat cancer. However, the efficacy of these vaccines in the clinic in patients with measurable disease remains questionable. We believe that the poor performance of peptide vaccines is due to their inability to generate sufficiently large CTL responses that are required to have a positive impact against established tumors. Peptide vaccines to elicit CTLs in the clinic have routinely been administered in the same manner as vaccines designed to induce antibody responses: injected subcutaneously and in many instances using Freund's adjuvant. We report here that peptide vaccines and poly-ICLC adjuvant administered via the unconventional intravenous route of immunization generate substantially higher CTL responses as compared to conventional subcutaneous injections, resulting in more successful antitumor effects in mice. Furthermore, amphiphilic antigen constructs such as palmitoylated peptides were shown to be better immunogens than long peptide constructs, which now are in vogue in the clinic. The present findings if translated into the clinical setting could help dissipate the wide-spread skepticism of whether peptide vaccines will ever work to treat cancer. [ABSTRACT FROM AUTHOR]

Cytotoxic T lymphocytes (CTLs) are effective components of the immune system capable of destroying tumor cells. Generation of CTLs using peptide vaccines is a practical approach to treat cancer. We have previously described a peptide vaccination strategy that generates vast numbers of endogenous tumor-reactive CTLs after two sequential immunizations (prime-boost) using poly-ICLC adjuvant, which stimulates endosomal toll-like receptor 3 (TLR3) and cytoplasmic melanoma differentiation antigen 5 (MDA5). Dendritic cells (DCs) play an important role not only in antigen presentation but are critical in generating costimulatory cytokines that promote CTL expansion. Poly-ICLC was shown to be more effective than poly-IC in generating type-I interferon (IFN-I) in various DC subsets, through its enhanced ability to escape the endosomal compartment and stimulate MDA5. In our system, IFN-I did not directly function as a T cell costimulatory cytokine, but enhanced CTL expansion through the induction of IL15. With palmitoylated peptide vaccines, CD8α+ DCs were essential for peptide crosspresentation. For vaccine boosts, non-professional antigen-presenting cells were able to present minimal epitope peptides, but DCs were still required for CTL expansions through the production of IFN-I mediated by poly-ICLC. Overall, these results clarify the roles of DCs, TLR3, MDA5, IFN-I and IL15 in the generation of vast and effective antitumor CTL responses using peptide and poly-IC vaccines. [ABSTRACT FROM AUTHOR]

The design of efficacious and cost-effective therapeutic vaccines against cancer remains both a research priority and a challenge. For more than a decade, our laboratory has been involved in the development of synthetic peptide-based anti-cancer therapeutic vaccines. We first dedicated our efforts in the identification and validation of peptide epitopes for both CD8 and CD4 T cells from tumor-associated antigens (TAAs). Because of suboptimal immune responses and lack of therapeutic benefit of peptide vaccines containing these epitopes, we have focused our recent efforts in optimizing peptide vaccinations in mouse tumor models using numerous TAA epitopes. In this focused research review, we describe how after taking lessons from the immune system's way of dealing with acute viral infections, we have designed peptide vaccination strategies capable of generating very high numbers of therapeutically effective CD8 T cells. We also discuss some of the remaining challenges to translate these findings into the clinical setting. [ABSTRACT FROM AUTHOR]

The present paper represents an experimental and theoretical study of the characteristics of natural convection and radiation heat transfer from a solid cylindrical rod inside a closed vessel under vacuum conditions. The effect of vacuum pressure on the heat transfer rates from the heating element by convection and radiation is clarified. The experimental results are used for Artificial Neural Network (ANN) training which is employed in the Adaptive Neuro Fuzzy Inference System (ANFIS) scheme to predict the heat transfer characteristics. The heat transfer predictions are performed for the solid rod under numerous heat fluxes for each vacuum pressure and the computed outcomes are compared with that predicted from the ANFIS. Outcomes indicated that for a constant heat flux, the convection heat transfer decrease with the reduction in pressure inside the vessel, while the radiation heat transfer will increase. Three methods of ANFIS are deemed in this work; grid partition, subtractive clustering and fuzzy C-mean clustering (FCM). However, the three methods appear an adequate fitting with the experimental data due to the high ability of these schemes at formulating input-output relations. A comparison with conventional correlation for the Nusselt number (Nu) has been implemented which proved the effectiveness and robustness of artificial intelligence in the generation of a direct relation between the effective parameters and the objective functions. Also, the main factors of ANFIS such as the number of membership functions (MFs), the number of clusters and the radius of clusters have been optimized to reach best performance. [ABSTRACT FROM AUTHOR]

• Mechanical properties and spalling of RPCs when exposed to high temperatures were tested. • After 200 °C, the strengths of all RPC mixes begin to drop as temperatures rise. • Glass or steel fibers have not inhibited the spalling of RPC in temperature between 400 and 500 °C. • RPC with steel/polypropylene fibers showed the best mechanical properties and spalling resistance up to 800 °C. • RPC mixes showed increasing mass loss and decreasing ultrasonic pulse velocity when temperature increases until spalling. Although reactive powder concrete (RPC) is a well-known composite that achieves high rates of compressive strength, its behavior during fire still questionable. This study investigates the mechanical characteristics of RPCs following exposure to high temperatures. RPCs were prepared using high quantities of cement, silica, quartz, and fine aggregates, very small quantities of water (w/c less than 0.25). The testing was carried out on five different RPC mixtures: control mixture (plain RPC), and four test mixtures (RPC with glass, steel, polypropylene (PP), and a hybrid of steel and PP fibers). RPCs were analyzed to explain the original and residual mechanical conduct and spalling during different temperatures between 25 °C and 800 °C. After exposure to elevated temperatures, specimens were tested for compressive, flexural, and indirect tensile strengths. Appearance and color change, spalling, mass loss ratio, and ultrasonic pulse velocity (UPV) were examined as well. Compressive and tensile strengths for RPC's mixes and flexural strength for RPC with steel fibers and RPC with steel and PP fibers gradually increases when specimens heated to 200 °C. However, the strengths of all mixes begin to drop as temperatures rise. Although RPC with steel and PP fibers had a high loss of its original compressive, tensile, and flexural strength at 800 °C, this RPC showed the best performance regarding spalling resistance and mechanical characteristics compared to the other types of RPCs. Also, all RPC mixes showedincreasing in mass loss and decreasing in UPV with temperature increase until spalling or became doubtful. [ABSTRACT FROM AUTHOR]

• Poly-ICLC a synthetic dsRNA mimic stimulates both TLR3 and MDA5. • Poly-ICLC is a potent IFN-I and IL-15 inducer through MDA5 stimulation. • Poly-ICLC is a strong adjuvant for peptide cancer vaccines promoting the expansion of T cells. • Systemic poly-ICLC enhances T cell infiltration through MDA5 stimulation and IFN-I production. • Clinically, poly-ICLC induces in situ autovaccination and enhances T cell responses. Immunotherapies have become the first line of treatment for many cancer types. Unfortunately, only a small fraction of patients benefits from these therapies. This low rate of success can be attributed to 3 main barriers: 1) low frequency of anti-tumor specific T cells; 2) lack of infiltration of the anti-tumor specific T cells into the tumor parenchyma and 3) accumulation of highly suppressive cells in the tumor mass that inhibit the effector function of the anti-tumor specific T cells. Thus, the identification of immunomodulators that can increase the frequency and/or the infiltration of antitumor specific T cells while reducing the suppressive capacity of the tumor microenvironment is necessary to ensure the effectiveness of T cell immunotherapies. In this review, we discuss the potential of poly-ICLC as a multi-functional immune modulator for treating cancer and its impact on the 3 above mentioned barriers. We describe the unique capacity of poly-ICLC in stimulating 2 separate pattern recognition receptors, TLR3 and cytosolic MDA5 and the consequences of these activations on cytokines and chemokines production. We emphasize the role of poly-ICLC as an adjuvant in the setting of peptide-based cancer vaccines and in situ tumor vaccination by mimicking natural immune responses to infections. Finally, we summarize the impact of poly-ICLC in enhancing T infiltration into the tumor parenchyma and address the implication of this finding in the clinic. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is caused by α1-antitrypsin deficiency (AATD) genetic susceptibility and exacerbated by infection. The current pilot study aimed at studying the combined effect of AATD and bacterial loads on the efficacy of COPD conventional pharmacotherapy. Fifty-nine subjects (29 controls and 30 COPD patients) were tested for genetic AATD and respiratory function. The bacterial loads were determined to the patients’ group who were then given a long acting beta-agonist and corticosteroid inhaler for 6 months. Nineteen percent of the studied group were Pi∗MZ (heterozygote deficiency variant), Pi∗S (5%) (milder deficiency variant), Pi∗ZZ (10%) (the most common deficiency variant), and Pi∗Mmalton (2%) (very rare deficiency variant). The patients’ sputum contained from 0 to 8 × 10 8 CFU/mL pathogenic bacteria. The forced vital capacity (FVC 6 ) values of the AAT non-deficient group significantly improved after 3 and 6 months. Patients lacking AATD and pathogenic bacteria showed significant improvement in forced expiratory volume (FEV 1 ), FEV 1 /FVC 6 , FVC 6 , and 6 min walk distance (6MWD) after 6 months. However, patients with AATD and pathogenic bacteria showed only significant improvement in FEV 1 and FEV 1 /FVC 6 . The findings of this pilot study highlight for the first time the role of the combined AATD and pathogenic bacterial loads on the efficacy of COPD treatment. [ABSTRACT FROM AUTHOR]

Dendritic cells are an important link between innate and adaptive immune response. The role of dendritic cells in bone homeostasis, however, is not understood. Osteoporosis medications that inhibit osteoclasts have been associated with osteonecrosis, a condition limited to the jawbone, thus called medication‐related osteonecrosis of the jaw. We propose that disruption of the local immune response renders the oral microenvironment conducive to osteonecrosis. We tested whether zoledronate (Zol) treatment impaired dendritic cell (DC) functions and increased bacterial load in alveolar bone in vivo and whether DC inhibition alone predisposed the animals to osteonecrosis. We also analyzed the role of Zol in impairment of differentiation and function of migratory and tissue‐resident DCs, promoting disruption of T‐cell activation in vitro. Results demonstrated a Zol induced impairment in DC functions and an increased bacterial load in the oral cavity. DC‐deficient mice were predisposed to osteonecrosis following dental extraction. Zol treatment of DCs in vitro caused an impairment in immune functions including differentiation, maturation, migration, antigen presentation, and T‐cell activation. We conclude that the mechanism of Zol‐induced osteonecrosis of the jaw involves disruption of DC immune functions required to clear bacterial infection and activate T cell effector response. [ABSTRACT FROM AUTHOR]