bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated techniques for analysis and monitoring of historical monuments: the case of San Giovanni al Sepolcro in Brindisi, southern Italy
Authors: Masini Nicola , Persico Raffaele , Rizzo Enzo , Calia Angela , Teresa Giannotta Maria , Quarta Giovanni , Pagliuca Antonello 
Published: September 2010

ABSTRACTIn this paper, an integrated prospecting performed in the atypical Romanesque church of San Giovanni al Sepolcro in Brindisi, southern Italy is presented. Ground‐penetrating radar (GPR) and ultrasonic data have been gathered on the circular load‐bearing colonnade of the monument. Here the results achieved on two of the columns are shown. The GPR data have been processed and have allowed to identify and focus the medieval internal metallic hinges joining the stone trunks in one of the columns and some reinforcement rebars in the other (and probably also the residual track of a restored fracture). The ultrasonic data have allowed to monitor the state of compactness and to assess the effectiveness of reinforcement interventions on the columns.
[2
Fe
–2
S
] Oxidative‐Stress Sensor
Sox
R
Bound to
DNA
Authors: Watanabe Satoshi , Miki Kunio 
Published: September 2010

Abstract
SoxR, a member of the MerR (mercury resistance regulator) family, is a transcriptional activator that contains a [2Fe‐2S] cluster. In entric bacteria, SoxR functions as an oxidative‐stress sensor. However, in other nonentric bacteria, its physiological role appears to be different. SoxR is activated by reversible one‐electron oxidation of the [2Fe‐2S] cluster. In the active state, SoxR and other MerR family proteins activate transcription from unique promoters, which have a long 19 or 20 bp spacer between the −35 and −10 operator elements, by untwisting the promoter DNA. The crystal structures of SoxR and its complex with the target promoter in the oxidized (active) state have been reported. The structure of SoxR monomer consists of a winged helix‐turn helix DNA‐binding domain, a dimerization helix, and a Fe‐S cluster‐binding domain. The SoxR dimer is formed by an antiparallel long coiled coil. The [2Fe‐2S] cluster of SoxR is completely solvent‐exposed and surrounded by an asymmetric environment stabilized by interaction with the other subunit. The asymmetrically charged environment of the [2Fe‐2S] cluster probably causes redox‐dependent conformational changes of SoxR. The structure of the SoxR‐DNA complex provides a structural framework of the transcriptional activation by DNA distortion in the MerR family.
Metal Trafficking Via Siderophores in Gram‐Negative Bacteria
Authors: Cobessi David , Schalk Isabelle J 
Published: September 2010

AbstractIron is essential for life for practically all living organisms and plays a number of key roles in biology. However, under physiological conditions, iron forms highly insoluble ferric hydroxide complexes, which severely limits its bioavailability. To overcome the problem of iron inaccessibility, bacteria excrete high‐affinity iron‐chelators termedsiderophoresthat are able to solubilize iron and deliver it into the cells. In gram‐negative bacteria, the uptake of ferrisiderophores always involves, at the level of the outer membrane, specific transporters of the family of the TonB‐dependent receptors. The energy required for this uptake is provided by the proton‐motive force of the inner membrane by means of an inner membrane complex comprising three proteins, TonB, ExbB, and ExbD. Structures of TonB‐dependent receptors have been solved in different conformations. They are all composed of a β‐barrel occluded by a globular domain. The binding site is highly specific for a single siderophore and is located in the lumen on the extracellular side of the barrel. Some TonB‐dependent receptors have an additional N‐terminal domain located in the periplasm. These receptors, in parallel to transport ferrisiderophores across the outer membrane, are involved in a signaling cascade regulating expression of genes involved in iron acquisition.
Hemophore
Has
A
Authors: Izadi‐Pruneyre Nadia , Wolff Nicolas , Delepierre Muriel , Lecroisey Anne 
Published: September 2010

Abstract

To satisfy their iron needs, several gram‐negative bacteria use a heme uptake system that relies on the secretion in the extracellular medium of heme‐binding proteins called
HasA hemophores
. These proteins scavenge heme from the host, either free or hemoprotein‐bound, and shuttle it to a specific outer membrane transporter, HasR, whereby it is internalized by a TonB‐dependent process and then used as an iron source. HasA hemophores form a family of highly conserved 19–20 kDa proteins without either sequential or structural similarities to other known proteins.

The HasA hemophore from

Serratia marcescens

, the most deeply studied, is described here with a special focus on its heme binding site and its unusual pair of axial ligands, a histidine and a tyrosine. The spectroscopic properties and the structures of the heme loaded and unloaded hemophore, free or complexed to the HasR transporter are presented. The mechanisms of heme capture by the hemophore and heme transfer to HasR are discussed.
SR
‐Like Protein
ZRANB
2
Authors: Mansfield Robyn E , Mackay Joel P 
Published: September 2010

Abstract
ZRANB2 is an SR‐like pre‐mRNA splicing factor that is conserved across vertebrates. It contains two RNA‐binding zinc finger domains at the N‐terminus, each of which includes a tetrahedrally coordinated zinc ion which is essential for the 3D fold of the domain, and an arginine/serine‐rich (RS) domain near the C‐terminus. The 3D structures of each zinc finger domain have been solved by NMR spectroscopy, and a crystal structure of the second zinc finger in complex with RNA is also available. Similar zinc finger domains, known collectively as RanBP2‐type zinc fingers, have been observed in other proteins and display a range of substrate‐binding abilities.
Ammonia Synthesis – Biological
Authors: Newton William E. 
Published: September 2010

Abstract

Although abundant, the N
2
gas in the Earth's atmosphere cannot be metabolized directly by most organisms and, consequently, cellular nitrogen is usually obtained in a “fixed” form, such as ammonia, nitrate, or as part of an organic molecule. These sources of “fixed” nitrogen are relatively scarce and represent the most‐often limiting nutrient in agricultural systems. Because organic nitrogen is incompletely recycled in the global ecosystem and because the available ammonia and nitrate are continually metabolized to N
2
, the biological reduction of N
2
occupies a pivotal position in the biogeochemical nitrogen cycle. This process, called nitrogen fixation, is performed only by prokaryotic microorganisms and it is catalyzed by the enzyme, nitrogenase. N
2
‐fixing microorganisms may be either free‐living or associated symbiotically with plants (or animals). The most agriculturally significant are the symbiotic microorganisms that live within the plant tissue in nodules, where they “fix” N
2
and deliver it to their host. The most commonly encountered nitrogenase is a molybdenum(Mo)‐based enzyme complex, but similar vanadium‐based and iron‐based enzymes are known plus a fourth unique system. The three‐dimensional structures of the two component proteins of Mo‐nitrogenase are known. Most nitrogenases also catalyze the reduction of many other substrates (e.g., C
2
H
2
, N
3
−
, HCN) in reactions that are inhibited by CO. Substrate reduction is accomplished by a series of association–dissociation cycles in which electrons (accompanied by MgATP hydrolysis) are transferred from the Fe‐protein component to the MoFe‐protein component on which substrates are bound and reduced. Each nitrogenase is genetically distinct and its biosynthesis, maturation, and activity are regulated by many genes, e.g., 20
nif
(nitrogen‐fixation‐related) genes are required for the single Mo‐nitrogenase of
Klebsiella pneumoniae
. A fundamental understanding of the biochemical action and genetic regulation of the nitrogen‐fixation components has significant potential for improving the economy of nitrogen fixation, minimizing water pollution, and increasing global food supplies.
Metal Nitrides
Authors: Sung Lee Jae , Hyeon Taeghwan 
Published: September 2010

AbstractTransition metal nitrides are characterized by high melting points, hardness, and resistance to corrosion. These physical properties are desired for catalytic materials that require resistance against attrition and sintering under reaction conditions. Since high specific area materials became available with clean surfaces, they have attracted considerable attention as catalysts for many reactions including hydrotreating (hydrodesulfurization, hydrodenitrogenation, and hydrodeoxygenation) hydrogenation, dehydrogenation, and ammonia synthesis. Metal nitrides demonstrate catalytic advantages over their parent metals in activity, selectivity, and resistance to poisoning. They have been found to be good catalysts for a number of reactions typically catalyzed by noble metals of high cost and limited supply. Structure, bonding, synthesis, and surface reactivity of transition metal carbides are discussed.
Reforming—Heterogeneous
Authors: Costa Bruno Dalla , Peralta María A. , Querini Carlos A. 
Published: September 2010

Abstract
In this article, the fundamental aspects of the catalytic naphtha reforming process are presented. The more important reactions that take place in a reforming reactor are discussed in detail. The discussion includes the analyses of the reaction mechanisms, the kinetics, and the thermodynamic as well as the effect that the reaction has on the product quality, as indicated by the research octane number and the Reid vapor pressure. Reforming catalyst preparation is also presented. The most important bimetallic catalysts, such as platinum–rhenium, platinum–tin., platinum–iridium, and platinum–germanium are compared. The particular features of the preparation of each of these catalysts are included in this article. The influence of catalyst composition, feed composition, operational variables (temperature, pressure, hydrogen to hydrocarbon ratio) on catalyst deactivation is addressed. Also, the effects that different poisons (metals, sulfur, basic compounds) have on catalyst activity and regenerability are briefly reviewed. Finally, the general procedure for catalyst regeneration is presented.
The Application of RecombinantDNATechnology in Medicinal Chemistry and Drug Discovery
Authors: Basu Soumitra , Oyelere Adegboyega 
Published: September 2010

AbstractDiscovering new drugs has never been a simple matter. From ancient times to the beginning of the nineteenth century, treatment for illness or disease was based mainly on folklore and traditional curative methods derived from plants and other natural sources. The isolation and chemical characterization of the principal components of some of these traditional medicines, mainly alkaloids and the likes, spawned the development of the modern pharmaceutical industry and the production of drugs in mass quantities. Consequently, the industry has undergone profound changes within the last millennium. As the companion chapters of this volume describe, the emphasis has changed from isolation of active constituents to creation of new, potent chemical entities. This evolution from folklore to science is responsible for the thousands of pharmaceuticals available worldwide at present.
Analog Design
Authors: Wermuth Camille G. 
Published: September 2010

AbstractAnalog design is usually defined as the modification of a drug molecule or of any bioactive compound in order to prepare a new molecule showing chemical and biological similarity with the original model compound. Excellent descriptions of the various possibilities of bioisosteric replacement are found in Cannon's chapter “Analog Design” published in the previous edition of this book. As a rule, it is expected that the analog exhibits some improvements over the original drug molecule, but sometimes financial motivations are predominant and justify the decision to prepare an analog in order to share market parts. Analog design is a fruitful procedure, easy to practice, and very popularly employed in pharmaceutical research from the beginning. Particularly, from the second half of the twentieth century, the production of very sophisticated molecules such as steroids, prostaglandins, anticancer drugs, and antibiotics became available and considerable advances could be made in medicinal chemistry. Analog design represents two‐third of all small molecule sales. Among the 29 new drugs launched in 2000, 24 were copies.
Hematopoietic Agents
Authors: Pelus Louis M. , Hoggatt Jonathan , Singh Pratibha , Sampath Janardhan 
Published: September 2010

AbstractAdult hematopoietic stem cells self‐renew, proliferate, and differentiate forming and maintaining appropriate levels of all the cellular components of blood as well as responding to increased demand. This lifelong process termed hematopoiesis is regulated in part by hematopoietic growth factors, interleukins, and chemokines. In an incredibly short period of time, since the discovery of culture systems and animal models that detected the growth of blood progenitor cells and identified the existence of hematopoietic stem cells in the 1960s, cytokines controlling their function have been identified, cloned, and brought into clinical practice. These agents have had a major impact on patient outcomes and the ability to treat disease. Clinicians now have the tools to modulate erythrocyte, neutrophil, and platelet production enabling treatment of congenital and iatrogenic conditions and harvest of hematopoietic stem and progenitor cells for curative hematopoietic transplantation. In this chapter, hematopoietic cytokines, mimetics, and other agents approved for use in humans are described. The fields of experimental hematology and cytokine research continue to expand and new interleukins continue to be identified. As our knowledge of hematopoietic cell function increases, so will our understanding of the cellular and molecular biology of cytokine actions, and the clinical use of these agents will be refined. The potential application of several newly defined cytokines is discussed as well as the potential for the future development of cytokines that directly regulate hematopoietic stem cell function.
Vitamins
Authors: Block John H. 
Published: September 2010

AbstractBiochemical processes cannot operate without vitamins. Vitamins have a variety of functions and some have dual roles. Vitamin A (retinol), in its active form, is both a regulator of cell division and a structural component of the visual pigment, rhodopsin. Vitamin D (cholecalciferol), after a two‐step hydroxylation in two different organs, is a hormonal regulator of calcium transport and cell division. Vitamin K is a coenzyme for carboxylation of glutamic acid. Vitamin E (α‐tocopherol) is a lipid‐soluble antioxidant. Thiamine (vitamin B1) is a coenzyme for decarboxylation of α‐keto acids and transketolase reactions in carbohydrate metabolism. Riboflavin (vitamin B2) is the active portion of the coenzymes FMN and FAD. Niacin/niacinamide are the active portions of the coenzymes NAD and NADP. The pyridoxine group (vitamin B6) is the coenzyme for amino acid metabolism including transaminations and decarboxylations. Pantothenic acid is a structural component of coenzyme A. Biotin is a coenzyme for four carboxylation reactions. Folic acid is a coenzyme for one‐carbon metabolism. Vitamin B12(cobalamin), with folic acid, is required for regeneration of methionine and, singly, is the coenzyme required for the rearrangement of methylmalonyl CoA. Ascorbic acid is a general free radical scavenger and required for at least eight biochemical reactions requiring oxidations. Vitamins A and D have provided the medicinal chemist with the basic structure to develop pharmacologically active molecules indicated for a variety of diseases. Some of the vitamins are toxic when taken in excess and have defined tolerable upper intake levels.
Cholinergics/Anticholinergics/Muscarinics/Nicotinics
Authors: Griffith Robert K. 
Published: September 2010

AbstractThis chapter quickly summarizes the cholinergic nervous system and the structures of muscarinic and nicotinic receptors. The structure–activity relationships of muscarinic agonists and antagonists are discussed with reference to attempts to develop of drugs selective for one of the five muscarinic receptors, both agonist and antagonists. The structure–activity relationships of agonists and antagonists of nicotinic receptors are presented with initial concentration on the neuronal nicotinic receptors and ending with neuromuscular blockers used in surgery.
Therapeutic and Diagnostic Agents for Parkinson's Disease
Authors: Booth Raymond G. , Neumeyer John L. , Baldessarini Ross J. 
Published: September 2010

AbstractThis chapter summarizes the neurobiology of Parkinson's disease and medicinal chemistry relevant to treatment of this neurodegenerative disorder with neuropsychiatric complications. The chapter also surveys basic clinical features of Parkinson's disease, its neuropathophysiology and etiology. Considered are genetic, maturational, metabolic, and environmental contributors to risk for the disease. Pharmacotherapy for Parkinson's disease includesl‐dopa to counter cerebral dopamine deficiency, direct dopaminergic agonists, and agents that prolong the actions ofl‐dopa or dopamine by preventing their metabolism by peripheral aromatic amino acid decarboxylase, catechol‐O‐methyltransferase, or monoamine oxidase. Additional drugs acting on nondopaminergic systems include muscarinic acetylcholine, adenosine, andl‐glutamate antagonists, as well as serotonin (5‐hydroxytryptamine) agonists. Agents used to diagnose Parkinson's disease and monitor its progression, include radioactive compounds used to image brainl‐dopa and dopamine neurotransporters and dopamine receptors. Finally, potential contributions are considered of medicinal chemistry to improve pharmacotherapy of Parkinson's disease.
Antihypertensives: Renin Inhibitors
Authors: Tice Colin M. , McGeehan Gerard M. , Claremon David A. 
Published: September 2010

AbstractRenin has been recognized as an attractive target for antihypertensive drugs since the 1950s. Intensive efforts in the 1980s focused on peptidomimetic hydroxy transition‐state isosteres led to many potent renin inhibitors. However, none of these compounds was developed as a drug. The advent of routine X‐ray crystallography of protein–ligand complexes provided additional insights that culminated in the discovery of aliskiren, a fully nonpeptidic renin inhibitor. Aliskiren, the first direct renin inhibitor to reach the market, was approved as an antihypertensive in 2007. Preliminary clinical trials suggest that aliskiren, and potentially other direct renin inhibitors, may have utility in end organ protection and congestive heart failure, in addition to hypertension.
AtherosclerosisI:LDLCholesterol Lowering
Authors: Burnett Duane A. , Davis Harry R. 
Published: September 2010

AbstractLowering LDL cholesterol in patients has been directly linked to lowering the incidence of cardiovascular disease and represents one of the most successful avenues of medicinal chemistry. This chapter discusses current drugs on the market and in development that effectively lower this key biomarker of heart disease. Mechanistic pathways presented are HMG‐CoA reductase inhibition, cholesterol absorption inhibition (NPC1L1 inhibition), and the use of bile acid sequestrants. New therapeutic targets, such as PCSK9, antisense apoB 100 and MTP inhibition, as well as combination therapy are also presented.
HIV
Integrase
Authors: Johns Brian A. 
Published: September 2010

Abstract
Integrase (IN) is one of only three viral enzymes encoded by the human immunodeficiency virus (HIV). The enzymatic activity of IN catalyzes the “integration” of viral double‐stranded DNA into host chromatin. Several steps including assembly, nuclear import, and gap repair are involved in the overall integration process, but two distinct biochemical steps are catalyzed by IN. The first step called 3′ processing allows for water to cleave the terminal dinucleotide on the respective ends of the viral DNA. The second discreet step called strand transfer facilitates the nicking of the host DNA by the recessed 3′ hydroxyl groups of the processed viral DNA. It is this second step of strand transfer that has been the focus of the bulk share of drug discovery efforts to date and the only step successfully inhibited by compounds that all fall into a class called two‐metal chelators. The science around the integrase enzyme is presented from a high‐level view of integration as part of the retroviral replication cycle through a molecular view of the biochemistry of the integration process involving nucleic acid strands. This chapter discusses inhibition of the strand transfer process and presents the two‐metal pharmacophore model and inhibitor design. The body of this work is focused on numerous classes of two‐metal chelation inhibitors of HIV‐1 integrase including several clinical candidates. The chapter concludes with a short survey of potential next‐generation compounds that have appeared in the literature through the end of 2008.
Antiprotozoal/Antiparasitic Agents
Authors: Woster Patrick M. 
Published: September 2010

AbstractCollectively, diseases caused by parasitic protozoa, includinghuman African trypanosomiasis(HAT), Chagas' disease and leishmaniasis, threaten more than 550 million people worldwide and cause nearly 150,000 deaths annually. The causative organisms for these diseases are unicellular trypanosomatid parasites of the generaTrypanosoma brucei,Trypanosoma cruzi, andLeishmaniasp., respectively. Drug therapies available for these diseases have not changed significantly in the past 50 years, and currently used agents are far less than satisfactory due to extreme toxicity, and because resistant parasitic strains are becoming more prevalent. These diseases are confined to impoverished or rural areas of Mexico, Central America, South America, sub‐Saharan Africa, the Middle East, Indonesia, and India. As such, drug discovery efforts against trypanosomatid diseases are limited because patients in underdeveloped areas cannot afford therapy, and because the infected population is too small to justify the required research expenditures. In addition, antiparasitic research in Third World nations is often hampered by economic issues and political turmoil, virtually assuring that the world's most impoverished people will continue to bear the major burden of parasitic disease. Clearly, there is a need for new anti‐infective agents that are potent, nontoxic and inexpensive to manufacture. In this chapter, the etiology of these diseases and their current treatment are described. The chapter also deals with medicinal chemistry aspects of efforts to identify new drug targets for parasitic diseases, and to produce novel inhibitors of trypanosomatid growth for use as antiparasitic agents.