Proton pump inhibitors (PPIs) were clinically introduced more than 25 years ago and have since proven to be invaluable, safe, and effective agents for the management of a variety of acid-related disorders. Although all members in this class act in a similar fashion, inhibiting active parietal cell acid secretion, there are slight differences among PPIs relating to their pharmacokinetic properties, metabolism, and Food and Drug Administration (FDA)-approved clinical indications. Nevertheless, each is effective in managing gastroesophageal reflux disease and uncomplicated or complicated peptic ulcer disease. Despite their overall efficacy, PPIs do have some limitations related to their short plasma half-lives and requirement for meal-associated dosing, which can lead to breakthrough symptoms in some individuals, especially at night. Longer-acting PPIs and technology to prolong conventional PPI activity have been developed to specifically address these limitations and may improve clinical outcomes.

Purpose: Because the combination of multiple modalities for cancer treatment is more likely to generate more potent therapeutic effects for the control of cancer, we have explored the combination of chemotherapy using cisplatin, which is routinely used in chemotherapy for advanced cervical cancer, with immunotherapy using DNA vaccines encoding calreticulin (CRT) linked to human papillomavirus type 16 E7 antigen (CRT/E7) in a preclinical model. Experimental Design: We characterized the combination of cisplatin with CRT/E7 DNA vaccine using different regimen for its potential ability to generate E7-specific CD8 + T-cell immune responses as well as antitumor effects against E7-expressing tumors. Results: Our results indicate that treatment of tumor-bearing mice with chemoimmunotherapy combining cisplatin followed by CRT/E7 DNA generated the highest E7-specific CD8 + T-cell immune response and produced the greatest antitumor effects and long-term survival as well as significant levels of E7-specific tumor-infiltrating lymphocytes compared with all the other treatment regimens. Furthermore, we found that treatment with cisplatin leads to the cellmediated lysis of E7-expressing tumor cells in vitro and increased number of E7-specific CD8 + T-cell precursors in tumor-bearing mice. In addition, we observed that E7-specific CD8 + T cells migrate to and proliferate in the location of TC-1tumors in mice treated with cisplatin. Conclusions: Thus, our data suggest that chemoimmunotherapy using cisplatin followed by CRT/E7 DNA vaccine is an effective treatment against E7-expressing tumors and may potentially be translated into the clinical arena.Multimodality treatments that combine conventional cancer therapies with antigen-specific immunotherapy have emerged as promising approaches for the control of cancer (see refs. 1, 2 for reviews). Antigen-specific immunotherapy is an attractive approach for the treatment of cancers because it has the potency to specifically eradicate systemic tumors and control metastases without damaging normal cells. A favorable approach to antigen-specific immunotherapy is the use of DNA vaccines based on their safety, stability, and ease of preparation (see refs. 3, 4 for review). However, DNA vaccines are poorly immunogenic. Thus, the potency of DNA vaccines needs to be enhanced by using methods to target DNA to the professional antigen-presenting cells and by modifying the properties of antigen-expressing antigen-presenting cells to boost vaccine-elicited immune responses. Several approaches have been developed to enhance DNA vaccine potency (see refs. 5, 6 for review).One particular approach to enhance DNA vaccine potency involves the use of intracellular targeting strategies to enhance MHC class I and class II antigen presentation in dendritic cells. Our previous studies have explored the linkage of calreticulin (CRT), a Ca 2+ -binding protein located in the endoplasmic reticulum (see ref. 7 for review) to a model tumor antigen, human papillomavirus type 16 (HPV-16) E7, for the develo...

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Among recently synthesized isoreticular metal-organic frameworks (IRMOFs), interpenetrating IRMOFs show high hydrogen adsorption capacities at low temperature and under ambient pressure. However, little is known about the molecular basis of their hydrogen binding properties. In this work, we performed grand canonical Monte Carlo (GCMC) simulations to investigate the effect of catenation on the interactions between hydrogen molecules and IRMOFs. We identified the adsorption sites and analyzed the adsorption energy distributions. The simulation results show that the small pores generated by catenation can play a role to confine the hydrogen molecules more densely, so that the capacity of the interpenetrating IRMOFs could be higher than that of the non-interpenetrating IRMOFs.

Cervical cancer is one of the most common cancers in women worldwide. Persistent infection with human papillomavirus (HPV) is considered to be the etiological factor for cervical cancer. Therefore, an effective vaccine against HPV infections may lead to the control of cervical cancer. An ideal HPV vaccine should aim to generate both humoral immune response to prevent new infections as well as cell-mediated immunity to eliminate established infection or HPV-related disease. In the current study, we have generated a potential preventive and therapeutic HPV DNA vaccine using human calreticulin (CRT) linked to HPV16 early proteins, E6 and E7 and the late protein L2 (hCRTE6E7L2). We found that vaccination with hCRTE6E7L2 DNA vaccine induced a potent E6/E7-specific CD8+ T cell immune response, resulting in a significant therapeutic effect against E6/E7 expressing tumor cells. In addition, vaccination with hCRTE6E7L2 DNA generated significant L2-specific neutralizing antibody responses, protecting against pseudovirion infection. Thus, the hCRTE6E7L2 DNA vaccines are capable of generating potent preventive and therapeutic effects in vaccinated mice. Our data has significant clinical implications.

The rare earth elements (REEs) such as neodymium, praseodymium, and dysprosium were successfully recovered from commercial NdFeB magnets and industrial scrap magnets via membrane assisted solvent extraction (MSX). A hollow fiber membrane system was evaluated to extract REEs in a single step with the feed and strip solutions circulating continuously through the MSX system. The effects of several experimental variables on REE extraction such as flow rate, concentration of REEs in the feed solution, membrane configuration, and composition of acids were investigated with the MSX system. A multimembrane module configuration with REEs dissolved in aqueous nitric acid solutions showed high selectivity for REE extraction with no coextraction of non-REEs, whereas the use of aqueous hydrochloric acid solution resulted in coextraction of non-REEs due to the formation of chloroanions of non-REEs. The REE oxides were recovered from the strip solution through precipitation, drying, and annealing steps. The resulting REE oxides were characterized with XRD, SEM-EDX, and ICP-OES, demonstrating that the membrane assisted solvent extraction is capable of selectively recovering pure REEs from the industrial scrap magnets.

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Purpose The purpose of this paper is to empirically investigate the negative casual relationships between organizational security factors (security systems, security education, and security visibility) and individual non-compliance causes (work impediment, security system anxiety, and non-compliance behaviors of peers), which have negative influences on compliance intention. Design/methodology/approach Based on literature review, the authors propose a research model together with hypotheses. The survey questionnaires were developed to collect data, which then validated the measurement model. The authors collected 415 responses from employees at manufacturing and service firms that had already implemented security policies. The hypothesized relationships were tested using the structural equation model approach with AMOS 18.0. Findings Survey results validate that work impediment, security system anxiety, and non-compliance peer behaviors are the causes of employee non-compliance. In addition, the authors found that security systems, security education, and security visibility decrease instances of non-compliance. Research limitations/implications Organizations should establish a mixture of security investment in their systems, education, and visibility in order to effectively reduce employees’ non-compliance. In addition, organizations should recognize the importance of minimizing the particular causes of employees’ non-compliance to positively increase intentions to comply with information security. Originality/value An important issue in information security management is employee compliance. Understanding the reasons behind employees’ non-compliance is a critical issue. This paper investigates empirically why employees do not comply, and how organizations can induce employees to comply by a mixture of investments in security systems, education, and visibility.