Lovelace Respiratory Research Institute
Lovelace Respiratory Research Institute
News Article | November 29, 2016
NOT FOR DISTRIBUTION TO U.S. NEWSWIRE SERVICES OR FOR DISSEMINATION IN THE UNITED STATES. ANY FAILURE TO COMPLY WITH THIS RESTRICTION MAY CONSTITUTE A VIOLATION OF U.S. SECURITIES LAWS. Further to the press releases dated October 6, 2016, and November 4, 2016, Santa Maria Petroleum Inc. ("Santa Maria", or the "Company") (NEX:SMQ.H) and Kalytera Therapeutics, Inc. ("Kalytera"), a company incorporated in the state of Delaware, wish to provide additional information with respect to the proposed merger between Kalytera, the Company and Kalytera Acquisition, Inc., a wholly-owned subsidiary of the Company incorporated in the state of Delaware ("Subco") which, subject to certain conditions and applicable shareholder, director and TSX Venture Exchange Inc. ("TSXV") approval, will result in a reverse takeover of Santa Maria by Kalytera (the "Proposed Transaction") pursuant to the policies of the TSXV. The resulting issuer from the Proposed Transaction (the "Resulting Issuer") will operate as a pharmaceutical company continuing the business of Kalytera. A draft filing statement outlining the definitive terms of the Proposed Transaction in accordance with the rules and policies of the TSXV has been submitted to the TSXV for review (the "Filing Statement"). The following table contains selected financial information in respect of Kalytera for the year ended December 31, 2015, the nine month period ended September 30, 2016 and certain selected pro forma financial information of the Resulting Issuer. Selected Information from Statements of Loss and Comprehensive Loss Subject to applicable shareholder and TSXV approval, on completion of the Proposed Transaction the management team and the board of directors of the Resulting Issuer will be comprised of the following individuals: Dr. Salzman is a physician, scientist, inventor, and biomedical entrepreneur. Dr. Salzman founded and built Inotek Pharmaceuticals, a 140-person biotech company that raised $92M in venture capital and concluded a $600M license with Genentech. As CEO of Inotek, Dr. Salzman brought numerous new chemical entities from conception to clinical stage testing, including a treatment for glaucoma that demonstrated clinical proof of concept in late Phase 2 clinical trials. In his role as founder and former Chairman of Orphan Technologies, Dr. Salzman developed three novel enzyme replacement therapies for rare metabolic diseases. Dr. Salzman has been funded by the U.S. National Institutes of Health, authoring 75 federal grants and receiving $102 million in federal grant funding. In addition to 175 peer-reviewed scientific publications, Dr. Salzman holds 40 patents in the fields of medicine, pharmacology, organic chemistry, and medical devices. Dr. Salzman attended Harvard Medical School and completed a pediatric internship and residency at Columbia University. He completed post-doctoral fellowship training in pediatric infectious disease, neonatology, pediatric critical care, and mucosal immunology at the Weizmann Institute of Science in Rehovot, Israel, Boston Children's Hospital Medical Center, and Massachusetts General Hospital. Dr. Salzman serves as Founder and Chairman of Radikal Therapeutics, Salzman Capital Ventures, Salzman Lovelace Investments, Tisbury Pharmaceuticals, and Respirometics, and is the Director of Drug Development at Lovelace Respiratory Research Institute. Mr. Stefansky is a principal of Bezalel Partners, a merchant bank that provides capital formation and strategic advisory services to mid-market private and small to mid-cap public companies in the healthcare, life sciences, and technology sectors. Mr. Stefansky brings more than 20 years of principal investment, investment banking, and operational experience to the Bezalel team. Prior to forming Bezalel, Mr. Stefansky was a founder and principal of Harborview Capital, a New York-based private equity firm. Seth Yakatan, has served as interim Chief Executive Officer of Kalytera from July 2014 to present. Mr. Yakatan brings more than twenty years of experience as a corporate finance professional, actively supporting emerging and established companies in achieving their corporate, financing, and asset monetization objectives. Seth currently serves as Vice President of Business Development at Invion, Ltd. a company, which he helped to found in August 2012. Seth currently serves as a director of FitLife Brands, Inc. and formerly of iSatori, Inc. since September 16, 2014, and served as interim Chief Financial Officer of iSatori, Inc. from April 3, 2015 until the consummation of the merger with FitLife in October 2015. Mr. Yakatan brings more than 24 years of experience as a life sciences business development and corporate finance professional, actively supporting small cap and major companies in achieving corporate, financing, and asset monetization objectives. Mr. Yakatan began his career as a venture capital analyst with Ventana Growth Funds and Sureste Venture Management, where he gained significant experience in creating successful venture- backed life science and biotechnology companies. Prior to founding Katan Associates in 2001, Mr. Yakatan worked in merchant banking at Union Bank of California, N.A., in the Specialized Lending Media and Telecommunications Group. During his six years there, he completed the placement of subordinated debt and private equity investments, exceeding $3 billion in transaction value. Mr. Yakatan is recognized as an expert in the valuation of life sciences companies, stemming from industry experience and academia. He has authored several publications and lectured and guest lectured at corporate workshops and universities on valuation theory, real-world practice and case studies and consulted to several state and provincial governments worldwide on commercialization and capital access initiatives. Mr. Yakatan holds an MBA in Finance from the University of California, Irvine, and a BA in History and Public Affairs from the University of Denver. Mr. Farrell has over 25 of years' experience as President and CEO, and as CFO with both public and private companies in the pharmaceutical, biotechnology and medical device industries, including extensive M&A experience, and experience in corporate finance and corporate partnering activities. Most recently, he served as CFO of Amarantus Bioscience Holdings, Inc. Previously, he served as President and CEO of Titan Pharmaceuticals from 2008 to 2009, and as Chief Financial Officer of Titan Pharmaceuticals from 1996 to 2008. From 1991 to 1996, he served as CFO, Corporate Group Vice President and General Counsel at Fresenius USA and Fresenius Medical Care where he completed 6 corporate partnership and M&A transactions totalling over $4 billion. Mr. Farrell holds a J.D. from the University of California's Hastings College of Law. Ronald Erickson is a senior executive with more than 30 years of experience in the high technology, telecommunications, micro-computer, and digital media industries. Mr. Erickson was the founder, in April 2003, of Visualant, a developer of unique spectral pattern matching technology. Mr. Erickson previously was Chairman, CEO and Co-Founder, of Blue Frog Media, a mobile media and entertainment company; Chairman and CEO of eCharge Corporation, an Internet-based transaction procession company; Chairman, CEO and Co-founder of GlobalTel Resources, a provider of telecommunications services; Chairman, Interim President and CEO of Egghead Software, Inc., a software reseller where he was an original investor; Chairman and CEO of NBI, Inc.; and Co-founder of MicroRim, Inc., the database software developer. Earlier, Mr. Erickson practiced law in Seattle and worked in public policy in Washington, D.C. and New York City. Additionally, Mr. Erickson has been an angel investor and board member of a number of public and private technology companies. In addition to his business activities, Mr. Erickson serves on the Board of Trustees of Central Washington University where he received his BA degree. He also holds a MA from the University of Wyoming and a JD from the University of California, Davis. He is licensed to practice law in the State of Washington. Jerome B. Zeldis is currently the CEO of Celgene Global Health and the Chief Medical Officer of Celgene Corporation, based in Summit, NJ. Dr. Zeldis serves as the Chief Executive Officer of Celgene Global Health and Chief Medical Officer of Celgene Corporation. He has been employed at Celgene Corporation since February 1997. Dr. Zeldis attended Brown University for an A.B., M.S., followed by Yale University for a M.Phil., M.D., Ph.D. in Molecular Biophysics and Biochemistry (immunochemistry). Dr. Zeldis trained in Internal Medicine at the UCLA Center for the Health Sciences and Gastroenterology at Massachusetts General Hospital and Harvard Medical School. He was Assistant Professor of Medicine at the Harvard Medical School, Associate Professor of Medicine at University of California, Davis, Clinical Associate Professor of Medicine at Cornell Medical School, and Professor of Clinical Medicine at the Robert Wood Johnson Medical School in New Brunswick, NJ. Prior to joining Celgene, Dr. Zeldis worked at Sandoz Research Institute and Janssen Research Institute in both clinical research and medical development capacities. He has served as a board member of several start-up biotechnology companies and is currently on the board of Semorex Corporation, PTC Corporation, Soligenix, Trek Therapeutics, and BionorPharma. He has published 122 peer reviewed articles and holds 43 U.S. patents. Jeff Paley has been an active clinician and consultant in the healthcare industry for the past 22 years, during which time Dr. Paley has consulted for over 30 analysts and portfolio managers in the biotechnology, pharmaceutical, specialty pharmaceutical, and medical technology arenas, reviewing the clinical, preclinical and regulatory pedigrees of numerous therapeutics and devices. Dr. Paley founded Access Medical Associates, PC in 2003, after spending five years on the full-time academic faculty of Weill Cornell Medical College, where he served as a Director of Clinical Research at the Cornell Internal Medicine Associates. At Weill-Cornell, Dr. Paley was a Principal or Co-Principal Investigator on several studies of diabetes, hypertension, and cholesterol disorders, including the landmark ACCORD study of intensive hyperglycemia, hypertension and hyperlipidemia management. Additional clinical interests include sleep disorders, weight loss, adult attention-deficit disorder, and cardiovascular disease prevention. He has served as a Director of Retrophin, Kellbenx Inc., and Remote Radiology, Inc. He trained at Harvard Medical School and completed a residency in Internal Medicine at Massachusetts General Hospital. He holds a Bachelor's Degree in mathematics and Rabbinic Ordination from Yeshiva University. Gary Leong is the Chief Scientific Officer of Aphria Inc., a Health Canada licensed producer of medical cannabis products. Gary has a personal background in quality assurance, quality control, quality system audits, international and domestic regulatory affairs and product research and development. Gary currently is the president of Neautrical Solutions Inc. located in Surrey, British Columbia. Prior to that, he was the Chief Scientific Officer at Jamieson Laboratories Limited. He began at Jamieson in the year 2000 as the Vice President of Scientific and Technical Affairs. He also held the position of Quality Control Manager at Boehringer Ingelheim Consumer Products: Quest Vitamins and Development Officer at Atomic Energy of Canada: Radiochemical Company. Gary's educational background began with a Bachelors of Science in Chemistry and has taken him most recently to an MBA in Quality Management from City University of Bellevue Washington. Gary is currently affiliated with The Life Sciences Working Team of Windsor-Essex Economic Development Corporation. In the past, he was a member of the Natural Health Products Directorate Program Advisory Committee and a board member of the Ontario Ginseng Innovation and Research Consortium. Victoria Rudman served as interim Chief Financial Officer of Kalytera from March 2015 through June 2016, and has served as Treasurer and Secretary of Kalytera from March 2015 to present. Ms. Rudman has over 25 years of professional experience in multiple aspects of leadership, operations, accounting, finance, taxation and fiscal management. Ms. Rudman has spent most of her career in Fortune 50 global investment bank and retail brokerage firms as well as small cap public companies and start-up ventures. She served as Chairman and CEO of Intelligent Living Inc. from 2011 through November 2014. Previously, Victoria held various technology controllership positions at Morgan Stanley and acted as a Vice President at Bear Stearns and Director of Business Planning & Strategy at Visual Networks, where she was the lead project manager for the entire technology business enterprise, including IPO and strategic M&A. Victoria holds a Bachelor of Business Administration in Public Accounting from Pace University, Lubin School of Business. In connection with the Proposed Transaction, Santa Maria will be holding a special shareholders' meeting on December 12, 2016 (the "Santa Maria Meeting") pursuant to which holders ("Santa Maria Shareholders") of common shares in the capital of Santa Maria ("Santa Maria Shares") will be asked to consider and, if thought appropriate, to approve: Further details regarding matters to be considered at the Santa Maria Meeting are provided in the Santa Maria management information circular dated November 11, 2016, which can be accessed through the Internet on the System for Electronic Document Analysis and Retrieval (SEDAR), which can be accessed at www.sedar.com. Sponsorship of the Proposed Transaction may be required by the TSXV unless an exemption or waiver from this requirement can be obtained in accordance with the policies of the TSXV. Santa Maria has applied to the TSXV for an exemption from the sponsorship requirement. There is no assurance that a waiver from this requirement can or will be obtained. The Proposed Transaction is expected to close in the fourth quarter of 2016. Completion of the Proposed Transaction is subject to a number of conditions, including but not limited to, TSXV acceptance. The Proposed Transaction cannot close until approval of the holders of common stock of Kalytera (the "Kalytera Shareholders") is obtained. Santa Maria has applied to the TSXV for an exemption from the Santa Maria Shareholder requirements in connection with the Proposed Transaction. There can be no assurance that the Proposed Transaction will be completed as proposed, or at all. Other conditions to the completion of the Proposed Transaction include, but are not limited to: As disclosed in the Corporation's November 4, 2016, press release, Kalytera completed a brokered private placement offering (the "Offering") of subscription receipts ("Subscription Receipts") pursuant to an agency agreement (the "Agency Agreement") with Clarus Securities Inc. (the "Lead Agent"), together with Haywood Securities Inc. (the "Agents") of 17,500,000 Subscription Receipts at a price of C$0.40 per Subscription Receipt (the "Offering Price") for gross proceeds of C$7,000,000. Each Subscription Receipt entitles the holder to receive, upon satisfaction of the escrow release conditions and without payment of additional consideration, one Resulting Issuer Share. Kalytera anticipates completing an additional private placement of subscription receipts for gross proceeds of C$1,333,333 (the "Subsequent Offering"). The Subsequent Offering is expected to be completed at a price per Subscription Receipt equal to the Offering Price, on substantially the same terms as the Offering. It is expected that the Agents in respect of the Subsequent Offering will be entitled to receive similar compensation as was provided in connection with the Offering. It is anticipated the Agency Agreement will be amended in connection with the Subsequent Offering. The Santa Maria Shares are currently halted from trading pending completion of the Proposed Transaction. All information contained in this press release with respect to Kalytera and Santa Maria was supplied by the respective parties, for inclusion herein, and each party and its directors and officers have relied on the other party for any information concerning the other party. The common shares of Santa Maria have not been and will not be registered under the United States Securities Act of 1933, as amended and may not be offered or sold in the United States absent registration or an applicable exemption from the registration requirement. This press release shall not constitute an offer to sell or the solicitation of an offer to buy nor shall there be any sale of the securities in any jurisdiction in which such offer, solicitation or sale would be unlawful. Completion of the Proposed Transaction is subject to a number of conditions including, but not limited to, completion of the Subsequent Offering and TSXV acceptance. Where applicable, the Proposed Transaction cannot close until the required shareholder approval is obtained. There can be no assurance that the Proposed Transaction will be completed as proposed, or at all. Investors are cautioned that, except as disclosed in the filing statement to be prepared in connection with the Proposed Transaction, any information released or received with respect to the Proposed Transaction may not be accurate or complete and should not be relied upon. Trading in the securities of Santa Maria should be considered highly speculative. Neither the TSXV nor its Regulation Services Provider (as that term is defined in the policies of the TSXV) has in any way passed upon the merits of the Proposed Transaction and associated transactions and neither of the foregoing entities has in any way approved or disapproved of the contents of this press release. This news release contains "forward-looking information" within the meaning of applicable securities laws for each of the Company and Kalytera, relating to the completion of Proposed Transaction, the Name Change, the Consolidation, the Continuance, the Contingent Board, the Fixed Plan, completion of the Subsequent Offering and associated transactions, including statements regarding the Proposed Transaction, the Name Change, the Consolidation, the Continuance, the Contingent Board, the Fixed Plan and the Subsequent Offering. Readers are cautioned to not place undue reliance on forward-looking information. Actual results and developments may differ materially from those contemplated by these statements depending on, among other things, the risks that the parties will not proceed with the Proposed Transaction, the Subsequent Offering, the Name Change, the Consolidation, the Continuance, the Contingent Board, the Fixed Plan and associated transactions, that the ultimate terms of the Proposed Transaction, the Subsequent Offering, the Name Change, the Consolidation, the Continuance, the Contingent Board, the Fixed Plan and associated transactions will differ from those that currently are contemplated, and that the Proposed Transaction, the Subsequent Offering,, the Name Change, the Consolidation, the Continuance, the Contingent Board, the Fixed Plan and associated transactions will not be successfully completed for any reason (including the failure to obtain the required approvals or clearances from regulatory authorities). The statements in this press release are made as of the date of this release.
News Article | October 26, 2016
ABBOTT PARK, Ill., October 26, 2016 -- Good nutrition helps build the foundation for a child's ability to learn, grow and thrive. For babies, the best nutrition is breast milk - there's nothing in the world like it - in part due to special prebiotics called human milk oligosaccharides (HMOs). HMOs, found naturally in breast milk, feed good bacteria in the gut. Researchers believe they may be one of the main reasons breastfeeding provides immune health benefits. Now, a new study offers news about HMOs for parents who need or choose to use infant formula. The study, published today in the Journal of Nutrition, shows that babies fed infant formula with a structurally identical version of 2'-fucosyllactose (2'-FL), the most abundant HMO found in most human milk, had an immune response more like breastfed babies. The prospective, randomized, double-blind clinical study looked at the immune response of 200 babies divided into feeding groups - exclusively breastfed, formula-fed without 2'-FL HMO and formula-fed with 2'-FL HMO. After six weeks, results showed that when comparing the breastfed group to the group fed formula without 2'-FL HMO, the levels of five immune markers were statistically different. Levels of these same markers, however, were nearly identical between the breastfed group and the group fed formula with 2'-FL HMO. "The first year of life is an important window for immune system development," said Edward Barrett, Ph.D., study author and Director of Translational Research at Lovelace Biomedical, part of the Lovelace Respiratory Research Institute. "These data are compelling for doctors and parents alike because we were able to show that the formula with 2'-FL HMO narrowed the gap between breast milk and formula in ways never seen before. We tested a number of immune markers, and found that specific signals of immune responses were the same in the breastfed and 2'-FL-formula fed babies." Excluding water, HMOs are the third most abundant ingredient in breast milk after fat and carbohydrates. There are hundreds of HMOs in human milk, and they are more than 100 times more abundant in breast milk than cow's milk. Like other prebiotics, HMOs support gut health, where 70 percent of the immune system exists. But, studies show that 2'-FL HMO also circulates in the bloodstream throughout the body. "Nothing can replace breast milk. But for those moms who need or choose to use formula, we are committed to providing the most scientifically advanced nutrition," said Rachael Buck, Ph.D., associate research fellow at Abbott and study author. "This latest research has led us to our biggest scientific breakthrough in infant formula in nearly a decade - the ability to nourish formula-fed babies with 2'-FL HMO. While it doesn't mean babies won't experience the normal illnesses that come with childhood, these data clearly show that formula with 2'-FL HMO can help strengthen babies' immune systems to be more like breastfed babies." The formula used in the study is available at major U.S. retailers and the Abbott store as Similac Pro-Advance and Similac Pro-Sensitive, both non-GMO. Abbott is the first company to add an HMO to infant formula. With more than 90 years of experience, Abbott conducts ongoing research to give babies the strongest possible start in the first year of life. Abbott is dedicated to unconditional nourishment and continues to offer parents new feeding options. Learn more about the science and benefits of HMOs on the Abbott nutrition newsroom. At Abbott, we're committed to helping people live their best possible life through the power of health. For more than 125 years, we've brought new products and technologies to the world -- in nutrition, diagnostics, medical devices and branded generic pharmaceuticals -- that create more possibilities for more people at all stages of life. Today, 74,000 of us are working to help people live not just longer, but better, in the more than 150 countries we serve. Connect with us at http://www. , on Facebook at http://www. and on Twitter @AbbottNews and @AbbottGlobal.
Morse D.,Harvard University |
Rosas I.O.,Harvard University |
Rosas I.O.,Lovelace Respiratory Research Institute
Annual Review of Physiology | Year: 2014
Despite public health campaigns discouraging smoking, 1,000 American children every day become smokers, ensuring that tobacco-related health complications will be with us for decades to come. Smoking is the greatest risk factor for both chronic obstructive lung disease and interstitial lung disease. The facts that not every smoker develops chronic lung disease and that lung pathology differs markedly among smokers indicate that individual susceptibility must be a central determinant of lung injury responses to cigarette smoke. Comparative examination of pathogenic mechanisms of smoke-induced lung disease can shed light on the homeostatic pathways critical to maintaining lung health. In this review, we explore common and divergent biological forces tilting the lung homeostatic balance away from health and toward emphysema or pulmonary fibrosis. We emphasize recent insights that highlight the greatest contrasts or similarities in the pathogenesis of these two chronic lung disease phenotypes. © Copyright ©2014 by Annual Reviews. All rights reserved.
Putman R.K.,Harvard University |
Rosas I.O.,Harvard University |
Rosas I.O.,Lovelace Respiratory Research Institute |
Hunninghake G.M.,Harvard University
American Journal of Respiratory and Critical Care Medicine | Year: 2014
Genetic studies hold promise in helping to identify patients with early idiopathic pulmonary fibrosis (IPF). Recent studies using chest computed tomograms (CTs) in smokers and in the general population have demonstrated that imaging abnormalities suggestive of an early stage of pulmonary fibrosis are not uncommon and are associated with respiratory symptoms, physical examination abnormalities, and physiologic decrements expected, but less severe than those noted in patients with IPF. Similarly, recent genetic studies have demonstrated strong and replicable associations between a common promoter polymorphism in the mucin 5B gene (MUC5B) and both IPF and the presence of abnormal imaging findings in the general population. Despite these findings, it is important to note that the definition of early-stage IPF remains unclear, limited data exist to definitively connect abnormal imaging findings to IPF, and genetic studies assessing early-stage pulmonary fibrosis remain in their infancy. In this perspective we provide updated information on interstitial lung abnormalities and their connection to IPF. We summarize information on the genetics of pulmonary fibrosis by focusing on the recent genetic findings of MUC5B. Finally, we discuss the implications of these findings and suggest a roadmap for the use of genetics in the detection of early IPF. Copyright © 2014 by the American Thoracic Society.
Belinsky S.A.,Lovelace Respiratory Research Institute
Annual Review of Physiology | Year: 2015
The reprogramming of the epigenome through silencing of genes and microRNAs by cytosine DNA methylation and chromatin remodeling is critical for the initiation and progression of lung cancer through affecting all major cell regulatory pathways. Importantly, the fact that epigenetic reprogramming is reversible by pharmacological agents has opened new avenues for clinical intervention. This review focuses on the tremendous progress made in elucidating genes and microRNAs that are epigenetically silenced in lung cancer and highlights how loss of function impacts cell phenotype and major signaling pathways. The article describes the utility of (a) an in vitro model using hTERT/Cdk4 immortalized human bronchial epithelial cell lines to identify genes and microRNAs silenced during premalignancy and (b) an in vivo orthotopic nude rat lung cancer model to evaluate response to epigenetic therapy. New insights regarding the advantage of aerosol delivery of demethylating agents and the concept of priming tumors for subsequent therapy are presented and discussed. Copyright © 2015 by Annual Reviews. All rights reserved.
Scott B.R.,Lovelace Respiratory Research Institute
Dose-Response | Year: 2011
Residential radon has been found to be associated with lung cancer in epidemiologi-cal/ecological studies and the researchers have inappropriately concluded that residential radon causes lung cancer. Their conclusion relates to the linear-no-threshold (LNT) hypothesis-based, risk-assessment paradigm; however, the LNT hypothesis has been invalidated in numerous studies. It is shown in this paper that our hormetic relative risk (HRR) model is consistent with lung cancer data where detailed measurements of radon in each home were carried out. Based on the HRR model, low-level radon radioactive progeny is credited for activated natural protection (ANP) against lung cancer including smoking-related lung cancer. The proportion B(x) (benefit function) of ANP beneficiaries increases as the average radon level x increases to near the Environmental Protection Agency's action level of 4 picocuries/L (approximately 150 Bq m- 3). As the average level of radon increases to somewhat above the action level, ANP beneficiaries progressively decrease to zero (B(x) decreases to 0), facilitating the occurrence of smoking-related lung cancers as well as those related to other less important risk factors. Thus, residential radon does not appear to cause lung cancer but rather to protect, in an exposure-level-dependent manner, from its induction by other agents (e.g., cigarette-smoke-related carcinogens). © 2011 University of Massachusetts.
Scott B.R.,Lovelace Respiratory Research Institute
Journal of Cell Communication and Signaling | Year: 2014
Humans are continuously exposed to ionizing radiation throughout life from natural sources that include cosmic, solar, and terrestrial. Much harsher natural radiation and chemical environments existed during our planet’s early years. Mammals survived the harsher environments via evolutionarily-conserved gifts ̶ a continuously evolving system of stress-induced natural protective measures (i.e., activated natural protection [ANP]). The current protective system is differentially activated by stochastic (i.e., variable) low-radiation-dose thresholds and when optimally activated in mammals includes antioxidants, DNA damage repair, p53-related apoptosis of severely-damaged cells, reactive-oxygen-species (ROS)/reactive-nitrogen-species (RNS)- and cytokine-regulated auxiliary apoptosis that selectively removes aberrant cells (e.g., precancerous cells), suppression of disease promoting inflammation, and immunity against cancer cells. The intercellular-signaling-based protective system is regulated at least in part via epigenetic reprogramming of adaptive-response genes. When the system is optimally activated, it protects against cancer and some other diseases, thereby leading to hormetic phenotypes (e.g., reduced disease incidence to below the baseline level; reduced pain from inflammation-related problems). Here, some expressed radiation hormesis phenotypes and related mechanisms are discussed along with their implications for disease prevention and therapy. © 2014, The International CCN Society.
Mauderly J.L.,Lovelace Respiratory Research Institute
Inhalation Toxicology | Year: 2014
The National Environmental Respiratory Center Program was initiated as an experiment to explore strategies for identifying the components of complex air pollution mixtures that cause health effects associated statistically with air pollution. A strategy involving multivariate analysis of a composition- concentration-response database was adopted. A novel database was created by exposing rodents daily for up to six months to one of four combustion-related mixtures and measuring respiratory, cardiovascular and general toxicological responses after one week or six months of exposure. The mixtures included multiple concentrations of diesel and gasoline engine exhaust, hardwood smoke and simulated downwind coal combustion emissions. After reporting the biological effects of each mixture and comparing effects among them, 47 significant effects were selected for multiple additive regression tree analysis to identify putative causal components. Although the four mixtures provided a database marginally sufficient for the analysis, the results suggested the putative causes of 19 significant effects with acceptable confidence. This article describes and critiques the Program and its strategy. The integrated results are presented in two accompanying papers, and mixture-specific results were presented in preceding papers, which are cited. The experiment demonstrated the potential utility of the general approach and identified certain cause-effect relationships for confirmatory studies. A follow-up study provided support for causation by the components implicated for one of those relationships. The advantages and disadvantages of the Program's management and funding strategies are discussed. © 2014 Informa Healthcare USA, Inc.
Kurtz M.,Lovelace Respiratory Research Institute
Information Technology and Libraries | Year: 2010
This paper provides an overview of Dublin Core (DC) and DSpace together with an examination of the institutional repositories of three public research universities. The universities all use DC and DSpace to create and manage their repositories. I drew a sampling of records from each repository and examined them for metadata quality using the criteria of completeness, accuracy, and consistency. I also examined the quality of records with reference to the methods of educating repository users. One repository used librarians to oversee the archiving process, while the other two employed two different strategies as part of the selfarchiving process. The librarian-overseen archive had the most complete and accurate records for DSpace entries.
Cheng Y.S.,Lovelace Respiratory Research Institute
AAPS PharmSciTech | Year: 2014
Aerosol delivery is noninvasive and is effective in much lower doses than required for oral administration. Currently, there are several types of therapeutic aerosol delivery systems, including the pressurized metered-dose inhaler, the dry powder inhaler, the medical nebulizer, the solution mist inhaler, and the nasal sprays. Both oral and nasal inhalation routes are used for the delivery of therapeutic aerosols. Following inhalation therapy, only a fraction of the dose reaches the expected target area. Knowledge of the amount of drug actually deposited is essential in designing the delivery system or devices to optimize the delivery efficiency to the targeted region of the respiratory tract. Aerosol deposition mechanisms in the human respiratory tract have been well studied. Prediction of pharmaceutical aerosol deposition using established lung deposition models has limited success primarily because they underestimated oropharyngeal deposition. Recent studies of oropharyngeal deposition of several drug delivery systems identify other factors associated with the delivery system that dominates the transport and deposition of the oropharyngeal region. Computational fluid dynamic simulation of the aerosol transport and deposition in the respiratory tract has provided important insight into these processes. Investigation of nasal spray deposition mechanisms is also discussed. © 2014 American Association of Pharmaceutical Scientists.