bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding and Mitigation of Underwater Sound in the Arctic
Authors: Ward John M. 
Published: December 2011

Abstract
Every human activity in the offshore Arctic, or anywhere offshore for that matter, emits some level of sound into the marine environment. Depending on intensity, and to some extent frequency, underwater sound can be a nuisance or even physically harmful to marine life.
The indigenous people of the Arctic Coastal Plain in Alaska depend on subsistence hunting of marine mammals for food and as an intrinsic part of their culture. Many have expressed concern that underwater sound from oil and gas industry activities may alter the behavior of these animals and make subsistence hunts more difficult or even permanently deflect the animals away from traditional hunting grounds. Understanding underwater sound and developing effective mitigation measures is important for operating in the Arctic marine environment.
This paper presents a brief discussion of underwater sound, regulations governing underwater sound from oil and gas exploration activities, practical implication of those regulations and outlines Shell's research program aimed at understanding underwater sound emitted by drilling operations offshore Alaska. Also presented are the concepts being developed to mitigate that sound. Although the research has been directed specifically at Alaska it is broadly applicable to other Arctic regions.

Introduction
Shell's objective in Alaska is to find and develop commercial hydrocarbon resources in the Chukchi and Beaufort Outer Continental Shelf. As with all Shell ventures, the company maintains high operational and social performance standards that will bring, with exploration success, economic benefits and new opportunities to communities across Alaska and the Northwest. Since returning to Alaska in 2005 Shell has embarked on an extensive field data acquisition, R&D and technology maturation effort aimed at supporting exploration and future development. This paper focuses on Shell's R&D program for mitigating underwater sound.
Every human activity in the offshore Arctic, or anywhere offshore for that matter, emits some level of sound into the marine environment. Depending on intensity, and to some extent frequency, underwater sound can be a nuisance or even physically harmful to marine life. Marine sound has been an ongoing issue for offshore oil and gas activities, primarily for seismic operations but also for construction and pipelaying activities in sensitive areas such as offshore Sakhalin Island, Russia. In seismic operations the concern is possible hearing damage to marine mammals and fish that are too close to the air gun arrays used. In Sakhalin the concern is disturbance of feeding behaviors of the endangered Western Grey Whale. In both cases industry and regulators have developed mitigating procedures to ensure minimum impact on health and behavior of marine mammal species. This paper describes efforts Shell is making to mitigate effects of marine sound from floating drilling rigs in Alaska. While the primary focus is Alaska, the results of this work is broadly applicable to other Arctic regions.
Development of Countermeasures for Bioterrorism in the United States
Authors: Levine Gregory H. , Handwerker Jeffrey L. 
Published: December 2011

AbstractThis chapter focuses on one element of biodefense‐the development of medical countermeasures to be used in advance of, or in response to, a bioterrorist attack. Unlike other areas of medicine, for which private market forces are generally sufficient to spur private industry to develop and market useful products, there are few market incentives to develop and market vaccines, diagnostics, and therapeutics for biodefense purposes. The majority of this chapter discusses the laws, regulations, and actions taken to date in the United States to spur the development of diagnostic, prophylactic, and therapeutic agents for biodefense.
Pain Management Market Overview
Authors: Holdcroft Anita 
Published: December 2011

Abstract
This chapter provides a detailed overview of the worldwide pain management arena. A structured approach to the analgesic market has been to identify the frequency and type of pain, how it is managed (e.g., mechanism‐based and evidence‐based approaches), and what combinations of therapies are used, what the unfulfilled needs are for over‐the‐counter (OTC) and prescribers, and how to improve therapeutic strategies to achieve maximum benefit for patients.
High‐Throughput Screening for Small‐Molecule Drug Discovery
Authors: Parker C. , Zhang J.‐H. 
Published: December 2011

AbstractThe aim of this chapter will be to review some of the high‐throughput screening (HTS) processes in current drug discovery, including assay technologies and screening strategies, the steps taken in assay development and validation, the screening process, and commonly used quality control measures. Also highlighted in this chapter are the analysis of HTS data and some of the approaches used for data mining for finding lead series. Finally, the chapter will reviews some of the emerging trends occurring in the science of biomolecular screening.
Molecular Screening for Therapeutic Agents
Authors: Damoiseaux R. 
Published: December 2011

AbstractThis chapter will provide an introduction to molecular screening, its underlying concepts, work flows, and novel applications as a research tool and for target discovery. Molecular screening has changed from a very specialized tool that was primarily used in drug discovery to an indispensable tool for research. The integration of genomic and chemical screening data will lead to a better understanding of disease mechanisms and enable a more efficient drug discovery process.
Antibodies for Human Diseases
Authors: Yu Guo‐Liang , Ni Jian 
Published: December 2011

AbstractMany years of research have resulted in the successful examples of immunotherapies for many diseases including cancers and inflammatory diseases. These new treatments are referred to as biological therapies‐such as monoclonal antibodies and vaccine therapies. The recent technological advances in monoclonal antibody (mAb) development have caused significant investment and interest in the pharmaceutical and biotech industry. Therefore, this chapter will highlight these new advances in the biological therapy arena.
PEGylation
Authors: Dhawan Sanju , Kapoor Deepak N. , Kapil Rishi , Kumar Manoj , Bansal Ankur 
Published: December 2011

AbstractPEGylation involves the masking of the surface of proteins and peptides by covalent coupling with soluble PEG. It is a method for optimizing pharmacokinetic and pharmacodynamic properties of therapeutic small drug molecules such as peptides and proteins. Thus, this chapter will focus on PEGylation as the modification of the surface properties of proteins and peptide or nonpeptide molecules via covalent attachment using a chemical modifier, PEG, either alone or in combination with other moieties. PEGylation has been exploited to increase the half life (t1/2), solubility, stability and decrease of the immunogenicity, and toxicity of enzymes, proteins, peptides, and nonpeptide molecules.
Discovery of Vaccine Adjuvants
Authors: Sharp Fiona A. , Lavelle Ed C. 
Published: December 2011

AbstractThe field of vaccine adjuvants is going through a “golden age” at present due in part to the developments in immunology. After almost 100 years of largely empirical developments in adjuvant research and development largely due to a poor understanding of how adjuvants work, the field is now developing on a new more rational plane. This chapter will provide a concentrated review of the parenteral routes of vaccination with a discussion of the past, present, and future achievements in this arena.
Oral Delivery of Macromolecules for the Development of Therapeutic Agents
Authors: Lee Hye J. , Choi Chanmi 
Published: December 2011

AbstractThis review will provide an overview of the existing approaches, the recent advances that have been made in oral delivery as related to proteins, and some future directions to consider followed by reviewing factors affecting oral protein absorption. It is likely that effective oral formulations for peptides and proteins will remain highly compound specific, but the principal concept is to preserve protein integrity before it reaches systemic circulation.
Antibiotic Development
Authors: Bettiker Robert L. , Gallagher Jason C. 
Published: December 2011

AbstractTwo major aspects of locating a new chemical entity (NCE) with potential antibiotic properties are (1) a source of compounds to screen and (2) the screening process itself. Pharmacokinetics and dynamics of the potential drug are two more areas of concern in antibiotic development. Although there are innumerable other steps in antibiotic development, this chapter will focus on just a few examples of these four areas.
Antimicrobial Resistance in Biofilms: A Sticky Situation
Authors: Queck Shu Yeong , Otto Michael 
Published: December 2011

AbstractThe increased recognition of the impact that biofilm formation has in the clinical and industrial settings has led to an explosion in the field of biofilm research over the past two decades. These studies led to the generation of several hypotheses to account for the exceptional ability of biofilm populations to resist antimicrobial killings. In this review, the various mechanisms of antimicrobial resistance will be examined with a specific emphasis on the predominant pathogens involved in biofilm‐associated infections, that is, staphylococci, Pseudomonas aeruginosa, and the fungal pathogenCandida albicans.
Drotrecogin Alfa Activated (Recombinant Human Activated ProteinC, Xigris)
Authors: Suh Byungse , Samuel Rafik 
Published: December 2011

AbstractOur understanding of the immunopathophysiology of sepsis has made extraordinary progress during the past several decades, although therapeutic advances during the similar period have been extremely slow. During the past decade several clinical trials demonstrated promising results showing reduced morbidity and mortality in sepsis, although some had mixed outcomes. These trials have supported four major approaches: (1) maintenance of good tissue oxygenation by aggressive management of fluid and blood transfusion, (2) intensive insulin therapy to maintain the euglycemia, (3) low‐dose corticosteroids, and (4) treatment with human recombinant activated protein C. These options will be briefly summarized in this chapter, but we will concentrate on the epidemiology, pathophysiology, and management of sepsis with emphasis on the use of drotrecogin alfa activated (DAA) in the management of sepsis.
Cardiovascular Disease: In‐Depth Look
Authors: Norgard Nicholas B. , Abu‐Fadel Mazen S. 
Published: December 2011

AbstractHeart disease is responsible for more deaths than any other disease. Recent advances in pharmacotherapy have helped to lessen the burden of heart disease but new technology is needed to maintain our progress. There are numerous potential cardiovascular therapeutic targets in various stages of development for the treatment of coronary heart disease, heart failure, and arrhythmias. The focus of this chapter will be to explore the current and novel pharmacological therapies in development for the treatment of cardiovascular diseases.
Ezetimibe and Cholesterol Absorption
Authors: Oswald Stefan , Siegmund Werner 
Published: December 2011

Abstract
This chapter will focus on the discovery and development of ezetimibe, its pharmacological and pharmacokinetic properties, as well as its therapeutic implications. Furthermore, the molecular mechanisms of cholesterol absorption, whose understanding was completely revolutionized by ezetimibe‐associated research, and novel therapeutic approaches affecting this promising pharmacological mechanism will be highlighted.
Cardiology—In‐Depth Look: Kinases as Therapeutic Targets in the Heart
Authors: Mauer Karin , Exaire J. Emilio 
Published: December 2011

AbstractAgents that target protein kinases have been used successfully in oncology, and several have been tested in cardiology with mixed results, suggesting that in the future selective protein kinase inhibitors may be used to treat cardiovascular disease. As this chapter will discuss, protein kinases are unraveling a new and exciting area of knowledge in cardiovascular disease. Developing new agents that selectively and safely inhibit protein kinases may provide a new therapeutic line of agents that may be used in ischemic heart disease, congestive heart failure, pulmonary and systemic hypertension, and arrhythmias.
Gastrointestinal Disorders: A Focus on Acid‐Suppressive Agents
Authors: Hemstreet Brian 
Published: December 2011

AbstractAcid‐related disorders are prevalent in many countries. Research over the last century into the physiology of gastric acid secretion has yielded valuable insight into pathophysiology of many of these disorders. The discovery that histamine, gastrin, and acetylcholine all effect the production of gastric acid paved the way for the development of the H2RAs and PPIs. These agents have subsequently revolutionized the treatment of many acid‐related disorders in clinical practice.
New Drugs and Nutraceuticals in the Treatment of Osteoarthritis
Authors: Henrotin Y. , Reginster J.‐Y. 
Published: December 2011

AbstractOsteoarthritis is a disease with a multifactorial etiology affecting all joint tissues and involving both biochemical and mechanical factors that act in synergy to degrade cartilage. Until now, OA treatments are limited to pain relief, even if some new drugs of the SYSADOA class have shown potential structure‐modifying effects. These drugs target cartilage as the endpoint of joint failure, underestimating the role played by subchondral bone and synovium in this process. However, recent studies emphasized the key role played by subchondral bone sclerosis and synovium inflammation in OA pathophysiology. Unfortunately, until now, there is no validated method for a reliable assessment of structural changes in these tissues, explaining that guidance documents edited by the official agencies and scientific societies are strictly focused on the assessment of cartilage changes.
Development of Anticytokine Agents for Rheumatoid Arthritis
Authors: Sherlock Jonathan , Buckley Christopher D. , Raza Karim 
Published: December 2011

AbstractIn this chapter, we will focus on cytokine‐based therapeutics. Not only are developments in the identification and targeting of cytokines vital, but the detailed pharmacology of the therapeutics themselves is of critical importance. The proof of concept demonstrated by the success of anti‐ tumor necrosis factor (TNF) agents, combined with the experimental ease with which cytokines can be investigated and manipulated, has opened the future of rheumatology to exciting new conceptual and therapeutic prospects.
Overview ofCNSNeuropharmaceuticals
Authors: Roxana‐Georgiana Tauser , Dan‐Stefan Antohe 
Published: December 2011

AbstractThe advances in the molecular neurosciences during “the decade of the brain” in conjunction with new genomic and proteomic sciences have radically changed the paradigm of central nervous system (CNS) drug design and development. The classical, chemistry‐based small‐molecule drug discovery has been broadened by the twenty‐first century biology‐driven paradigm of large‐molecule neuropharmaceuticals: peptides, recombinant proteins, monoclonal antibodies, antisense oligonucleotides, and gene therapy. As this chapter will discuss, however, despite this progress in the field of neuroproteomics and rational drug design strategies, there is still a high failure rate of the candidates in later stages of projects and consequently an unsatisfied demand for novel neurotherapeutic and neurodiagnostic medicines. Therefore, CNS drug discovery and CNS drug targeting must be merged early in the CNS drug development process in order to obtain neuropharmaceuticals active in the brain following systemic administration.
Thinking Outside the Box in Alzheimer Disease Treatment
Authors: Castellani Rudy J. , Marlatt Michael W. , Nunomura Akihiko , Moreira Paula I. , Lee Hyoung‐Gon , Casadesus Gemma , Zhu Xiongwei , Perry George , Smith Mark A. 
Published: December 2011

AbstractSporadic Alzheimer disease (AD) is a complex process that develops over decades and involves biochemical dysfunction in multiple arenas. While amyloid‐β and phosphorylated tau are attractive targets for therapy, both accumulate as late phenomena in the disease process, particularly in sporadic disease. The lack of specificity of plaques and tangles for AD, particularly in early and intermediate stages of the disease, and with advanced age, highlight the need to look beyond amyloid‐β and tau for early pathogenic factors and treatment. Moreover, as this chapter will discuss, the strides that have been made in lipid metabolism with statins, and in neuroprotection from anti‐infl ammatory treatment, as well as antiexcitotoxic and cholinergic treatment, emphasize the point that AD is complex and that any one strategy or construct may not be sufficient.
Aromatase Inhibitors for Breast Cancer
Authors: Hossain Akm , Abraham Jame 
Published: December 2011

Abstract
The continued evolution of endocrine therapy has contributed to many therapeutic options for patients with breast cancer. In 1998, Oxford overview demonstrated that the selective estrogen receptor modulator (SERM) tamoxifen (TM) was equally effective in pre ‐ and postmenopausal breast cancer patients. As this chapter will discuss, the development of aromatase inhibitors (AIs) added a new option in addition to SERMs for the treatment of breast cancer.
Evolution of Selective Estrogen and Androgen Receptor Modulators: Status of Current Therapy and New Drug Development
Authors: Wurz Gregory T. , DeGregorio Michael W. 
Published: December 2011

AbstractPrior to the discovery of nonsteroidal selective estrogen and androgen receptor modulators (SERMs and SARMs), the only available treatment modalities for conditions such as menopausal symptoms and postmenopausal osteoporosis in women, and the symptoms associated with hypogonadism in men, were steroid based. As this chapter will discuss, recent clinical trial data have shown that the long‐term use of hormone replacement therapy in postmenopausal women is associated with an increased risk of breast cancer and may increase the risk of coronary heart disease and dementia, contrary to the results of previous observational studies. There are also concerns that androgen replacement therapy in hypogonadal men may pose a risk to prostate health, in addition to the difficulties inherent with the delivery of steroidal androgens. Thus, there is now great interest in developing nonsteroidal, orally bioavailable therapies, that is, SERMs and SARMs, that can provide the respective benefits of estrogens and androgens while minimizing their associated side effects.
Development of Therapeutic Agents: The Maternal–Fetal Perspective
Authors: Gedeon C. , Bournissen F. Garcia , Koren G. 
Published: December 2011

AbstractOur objective in this chapter will be to present the state of relevant research and to stimulate interest in research efforts aimed at developing selective drugs for use in pregnancy. The hope is to explore therapeutic strategies that can either reduce unnecessary fetal exposure to drugs required by the mother or, in some instances, reduce maternal exposure to drugs destined for fetal treatment.
History of Antipsychotic Drug Development
Authors: Gollapudi Shankar S. , Radhakrishnan Rajan 
Published: December 2011

AbstractCurrently, there are several classes of antipsychotic drugs available to psychiatrists to treat schizophrenia. Recent studies have shown that taking antipsychotic medications consistently is crucial and necessary to manage the symptoms and to control the risks of relapse. This chapter will review the history of antipsychotics starting with the birth of typical antipsychotics developed over a half century ago, the current newer safer atypical agents for treatment of schizophrenia, and novel emerging therapies being developed in the new millennium.
Therapeutic Drug Development for Kidney Diseases
Authors: Rosner Mitchell H. , King Joshua , Monteleone Peter 
Published: December 2011

AbstractThis chapter will explore drug development across the spectrum of kidney disease. This ranges from acute kidney injury (AKI) to specific causes of chronic kidney disease (CKD) such as polycystic kidney disease. Drugs to effectively manage the complications of CKD are also discussed. Finally, in each section, common obstacles to drug development for this disease state are discussed.
Development of Therapeutic Agents: Methods and Approaches in the Development of Vaccines Against Protozoan Parasites
Authors: Ivory Catherine , Chadee Kris 
Published: December 2011

AbstractParasitic infections make up a large percent of diseases in tropical countries and pose a significant threat to human health worldwide. Parasites are complex pathogens associated with chronic disease, high reinfection rates, and host immune depression. Furthermore, parasitic infections, unlike most viral and bacterial infections, are more complex and chronic, requiring special consideration when developing therapeutic agents. As this chapter will discuss, designing strategies against parasitic infections demands that scientists address the multifactorial aspects of special pathogens. The challenge in developing therapeutic agents against parasites lies in the nature of the parasites and their close relationship with both human immunity and anthropogenic activities.
Toxicology
Authors: Duffus John H. 
Published: December 2011

AbstractThe main objective of toxicology is to prevent harmful effects of useful substances, including therapeutic agents. For new pharmaceutical agents, extensive toxicity and efficacy data are required, including data from volunteer studies in humans. Pharmaceutical agents, at appropriate dose levels, are expected to have a beneficial effect on patients. Other substances, in normal use, whatever their beneficial effects, should have no biological effects on people. This includes pesticides, which, when used as intended, should produce a biological effect in pests without any effect on humans. This chapter on toxicology will provide a basic overview of the current state of toxicological research.
Development of Phosphodiesterase 4 Inhibitors for Allergic and Nonallergic Inflammatory Diseases of the Airways
Authors: Giembycz Mark A. 
Published: December 2011

AbstractThe decision by the pharmaceutical industry to develop second‐generation PDE4 inhibitors for the treatment of allergic and nonallergic inflammatory diseases of the airways is based on a conceptually robust hypothesis that is supported by a wealth of preclinical data. Therefore, if shown to be potentially disease modifying in clinical trials, PDE4 inhibitors will offer physicians a novel class of drug to treat patients with inflammation that may be refractory to other drugs such as glucocorticoids. That said, as this chapter will discuss, further major refinements in the design and/or use of PDE4 inhibitors are still necessary to improve their therapeutic ratio if major clinical benefit is to be achieved.
In Situ Fully Light‐Driven Switching of Superhydrophobic Adhesion
Authors: Li Chao , Zhang Yuanyuan , Ju Jie , Cheng Futao , Liu Mingjie , Jiang Lei , Yu Yanlei 
Published: December 2011

AbstractAn in situ fully light‐driven switching of superhydrophobic adhesion is demonstrated based on simply spin‐coating a hydrophobic azo‐polymer on an optimized micro‐nanopost arrayed silicon substrate. Furthermore, the detailed designing principles are discussed, which might shed light on efficient exploitation of superhydrophobic liquid/solid interfaces for smart microfluidic control.