Books by Subject


  • 2012
    Debanti Sengupta.
    There is a tremendous need for muscle regeneration therapies to replace tissue that is lost due to disease or injury. This work is focused on developing engineered replacement therapies for lost or damaged skeletal and cardiovascular muscle tissue. In order to create viable, clinically relevant regenerative therapies, I have used recombinant protein technology to synthesize a family of protein-engineered biomaterials that incorporate critical cues for the recapitulation of in vivo muscle tissue conditions. Crucially, these biomaterials allow the independent tuning of multiple biomaterial properties including cell adhesivity, biomaterial stiffness, and topographical cues. Each of these biomaterial properties impacts muscle cell behavior independently as well as in concert. I have exploited the range of biomaterial tunability available to us to identify biomaterial conditions that enable production of striated muscle tissue using primary human skeletal muscle myoblasts (hMBs) that may be electrically paced. I have further demonstrated that mouse model skeletal muscle cell lines do not accurately recapitulate primary human myoblast behavior in response to biomaterial properties, particularly with respect to integrin-matrix interactions. Importantly, the expression of mature muscle markers that indicate muscle cell differentiation could be accelerated simply by changing biomaterial stiffness and introducing biomaterial microtopography. Finally, as demonstration that this protein-engineered biomaterial strategy may have application in the regeneration of myocardial as well as skeletal muscle tissue, cardiomyocytes derived from human embryonic stem cells exhibited good cell viability and improved contractility on these biomaterials. This thesis represents important advancements in the development of regenerative muscle tissue engineered constructs.
  • 2005 Springer
    Raj B. Durairaj.
  • 2006 CRCnetBASE
    edited by Bharat B. Aggarwal and Shishir Shishodia.
  • 2010
    Alicia Carolina Gutierrez.
    A facile and 100% regioselective cycloisomerization--6-pi-cyclization method for obtaining pyridines is described. The unsaturated ketones and aldehydes derived from the cycloisomerization of primary and secondary propargyl diynols in the presence of CpRu(MeCN)₃PF₆ are converted to 1-azatrienes which in turn undergo a subsequent electrocyclization--dehydration to provide pyridines with excellent regiocontrol. The ruthenium-catalyzed cycloisomerization is a mild, atom-economical method for obtaining the requisite dienone and dienal substrates. The cycloisomerization--6-pi-cyclization sequence may be carried out in one pot or in two independent steps. Additionally, the azatriene cyclization may be carried out in 1-3 hours under microwave irradiation or, for more sensitive substrates, at lower temperatures for longer periods of time (6--24 hours at 90 °C). An atom-economical method for the convenient synthesis of tetrahydropyrans and tetrahydrofurans is also described. Enones and enals derived from the [IndRu(PPh₃)₂Cl]-catalyzed redox-isomerization of primary and secondary propargyl alcohols undergo a subsequent intramolecular conjugate addition to provide cyclic ethers in excellent yields. Lastly, we have developed complementary methods for the transition metal-catalyzed enyne cycloisomerizations of cyclic olefins. By using distinct ruthenium and palladium catalysts, decalins and 7,6-bicycles can be obtained with dichotomous stereochemical outcomes. The change in mechanism that accompanies the change in metal affords trans-fused 1,4-dienes with ruthenium and their cis-fused diastereomers under palladium catalysis. In the reactions under ruthenium catalysis, a coordinating group is required, and acts to direct the metal to the same side of the carbocycle, resulting in the observed trans diastereoselectivity. Subtle changes in the carbocyclic substrate led to the discovery of a heretofore-unobserved mechanistic pathway, providing bicyclic cycloisomerization products under palladium catalysis, tricyclic products under ruthenium catalysis in DMA, and a 1:1 mixture of the two under ruthenium catalysis in acetone. The different coordination requirements of the two paths allow for the reaction to be shuttled through the metallacycle pathway (generating tricyclic products) when DMA is used as a solvent. This method of obtaining these cyclobutene products complements the existing methods for catalyzing the [2+2] cycloaddition of alkynes. While other methods have been demonstrated for larger ring sizes with palladium, and for specific alkyne termini with platinum and gold, this method is unique in its substrate scope. To the best of our knowledge, this is the first example of a [2+2] cycloaddition catalyzed by CpRu(MeCN)₃PF₆.
  • 2009 CRCnetBASE
    T.S.S. Dikshith.
  • 2013
    William Hazen Parsons.
    Voltage-gated sodium channels (NaV) serve an essential role in physiology. Accordingly, their dysfunction is associated with a number of human diseases and disorders, including epilepsy, cardiac arrhythmias, and chronic pain conditions. Designed by Nature as a chemical weapon, the naturally occurring channel blocker (+)-saxitoxin (STX) can be repurposed as a tool for studying these large integral membrane proteins. Access to new toxin derivatives through de novo synthesis offers a unique strategy to probe NaV structure and function, circumventing key limitations associated with existing methods for studying these proteins. The preparation and electrophysiological evaluation of an expanded library of N21-modified STX analogues is described herein. Characterization of the binding properties of these nanomolar NaV inhibitors has contributed to the development of an enhanced model for the structure of the inner pore of the channel. A select set of STX-fluorophore conjugates that bind reversibly to NaV with submicromolar potency serve as fluorescent markers of channels in living cells to study channel motility in the cell membrane. By contrast, maleimide-conjugated STX derivatives can be engineered to act as irreversible inhibitors of ion conductance when applied to wild-type NaV isoforms. The unique binding behavior of these derivatives has been leveraged to develop a new class of NaV probes for use in live cell imaging experiments and protein profiling studies. Maleimide-toxin conjugates with bioorthogonal reactive groups have been synthesized and can be employed for ligation of visualization and isolation tags to covalently modified channels. Appendage of fluorine-18 to a modified STX affords a probe for studying NaV expression in living subjects. An efficient synthetic route yields a derivative that binds with nanomolar affinity to several NaV isoforms. Biodistribution, autoradiography, and PET-MRI imaging studies demonstrate accumulation of the radiotracer at the site of injury in a rat model of neuropathic pain. This uptake correlates with the previously reported upregulation of NaV isoforms at this site, validating the utility of this probe as a NaV imaging agent. Collectively, these STX derivatives, uniquely available through chemical synthesis, represent a novel set of molecular probes for studying NaV function in vitro and in vivo.
  • 2013
    Dennis Nick Fournogerakis.
    My graduate studies have been focused on two separate projects that are unified by the theme of step economy and exemplify two major concepts within step economy. The first of these is the development of new reactions or serial reactions aimed at creating ways to achieve significant molecular complexity increases in a short synthetic sequence to access targets of value. Complementary to this is the concept of function-oriented synthesis, which involves the design and synthesis of novel structures of value that contribute to our understanding of the biological effects of the compound and results in the refinement of lead structures to produce clinically more optimal candidates. Chapter 1 reviews the development of serial cycloadditions and their application in organic synthesis. Serial cycloadditions are valuable reactions for organic chemists because of the significant increase in molecular complexity observed in a single step. The review separates the collective body of work into non-catalyzed serial cycloadditions and transition metal catalyzed cycloadditions. The non-catalyzed variants can involve the combining of simple starting materials into polycyclic ring systems, but are typically limited to more activated dienes or dienophiles. The transition metal mediated processes developed more recently have utilized unactivated reaction partners but, typically, rely on complex starting substrates. This review highlights the potential opportunity to develop serial cycloadditions that combine simple unactivated reaction partners to produce scaffolds of interest. Chapter 2 discusses the development of 4-trimethylsilyl-but-2-yn-1-ol as a regioselective butatriene equivalent for serial [5+2]/vinylogous Peterson olefination/[4+2] cycloadditions to produce linear polycyclic ring systems. 4-trimethylsilyl-but-2-yn-1-ol behaves as initial 2-carbon component in the Rh-catalyzed [5+2] cycloaddition with vinylcyclopropane and then subsequently eliminates to a diene that can be utilized for further elaboration. A diverse set of dienophiles was evaluated for the second cycloaddition and both alkynes and alkenes were found to be suitable reaction partners, with up to nearly quantitative yields obtained. The reaction was utilized to access a key intermediate for proposed simplified analogs of staurosporine. Chapter 3 begins by describing the current state of the HIV pandemic and the limitations of the current therapeutic options (Highly Active Antiretroviral Therapy - HAART). The principal barrier to developing a cure for HIV is the latent reservoir that is insusceptible to HAART. The natural product prostratin is a clinical lead for a promising HIV eradication strategy that involves the deliberate activation of these latent reservoirs. Novel analogs of prostratin were synthesized and found to exhibit activity that greatly exceeded the natural product in multiple biological assays. Most impressively, a lead analog was found to potently induce HIV expression in patient samples from HIV-infected individuals on suppressive HAART. Chapter 4 delves into the design, synthesis, and evaluation of 2nd-generation analogs of prostratin. These analogs were inspired by the realization of a key intramolecular hydrogen bond in prostratin and can be accessed in a more step-economical fashion than the original analogs because they circumvented a problematic deoxygenation step in the original synthesis. The new analogs that incorporated ether functionality at C12 of prostratin were found to have higher affinities for PKC, the presumed biological target for prostratin, and more potent induction of latent HIV in vitro and ex vivo. Finally, Chapter 5 describes the further manipulation of the prostratin scaffold in hopes of obtaining properties of a clinically optimized agent. Novel transformations on the scaffold are reported and preliminary biological evaluation of the new analogs is discussed. Based on these results, new information was obtained about the tolerability of the protein binding pocket for certain modifications and this will facilitate the future development of novel PKC modulators.
  • 2011
    Hsiao-lu Lee.
    Since the first successful detection single molecules over two decades ago, single-molecule spectroscopy has developed into a burgeoning field with a wealth of experiments at room temperature and inside living cells. Probing asynchronous and heterogeneous populations in situ, one molecule at a time, is not only desirable, but critical for many biological questions. Further, super-resolution imaging based on sequential imaging of sparse subsets of single molecules, has seen explosive growth within the last five years. This dissertation describes both the application of live-cell single-molecule imaging as an answer to important biological questions, and development and validation of fluorescent probes for targeted super-resolution imaging.
  • 2012
    Whitney Clara Duim.
    Single-molecule, super-resolution fluorescence microscopy is a powerful technique for studying biological systems because it reveals details beyond the optical diffraction limit (on the 20-100 nm scale) such as structural and conformational heterogeneity. Further, single-molecule imaging measures distributions of behaviors directly through the interrogation of many individual molecules and reports on the nanoscale environment of molecules. Sub-diffraction imaging adds increased resolution to the advantages of fluorescence imaging over the techniques of atomic force microscopy and electron microscopy for studying biological structures, which include imaging of large fields of view in aqueous environments, specific identification of protein(s) of interest by fluorescent labeling, low perturbation of the system, and the ability to image living systems in near real-time (limited by the time required for super-resolution sequential imaging). This dissertation describes the application of single-molecule and super-resolution fluorescence imaging to studying the huntingtin (Htt) protein aggregates that are a hallmark of Huntington's disease and that have been implicated in the pathogenesis of the disease. The intricate nanostructures formed by fibrillar Htt aggregates in vitro and the sub-diffraction widths of individual fibers mark the amyloids as important targets for high-resolution optical imaging. The characterization of Htt aggregate species is critical for understanding the mechanism of Huntington's disease and identifying potential therapies. Following an introduction to single-molecule, super-resolution imaging and Huntington's disease in Chapter 1, Chapter 2 describes the single-molecule methods, experimental techniques, Htt protein sample preparations, and data analysis performed in this dissertation. Chapter 3 discusses the development of super-resolution imaging of Htt protein aggregates and the validation of the images by atomic force microscopy. Chapter 4 continues the study of Htt by one- and two-color super-resolution with imaging of Htt protein aggregates over time from the initial protein monomers to the large aggregate assemblies of amyloid fibers. In Chapter 5, I detail our progress to-date in studying the earliest stages of Htt aggregation using zero-mode waveguide technology. Chapter 6 concludes the dissertation with a discussion of the results from additional projects comprising the effect of chaperonin proteins on Htt aggregation, extension of super-resolution Htt imaging to three dimensions, and cellular imaging of Htt aggregates. The future directions for these exciting projects are summarized with the expectation that research efforts directed in these areas will contribute to our understanding of Htt aggregation and Huntington's disease.
  • 2012
    Armando Ricardo Hernández.
    This thesis project describes the synthesis and use of size-expanded ribonucleic acids (xRNAs) as unnatural components in small interfering RNAs (siRNAs), which serve as a novel set of steric probes for investigating and identifying size restrictions that exist in the active site of the RNA-induced silencing complex (RISC), a critical protein complex in the RNA interference (RNAi) mechanism. xRNAs are analogous to natural RNAs, in which they retain canonical Watson Crick base-pairing groups, except their nucleobases are expanded linearly by 2.4 Å via benzo-fusion. In this report, the synthesis of the entire set of four xRNA nucleosides and their photophysical properties are described. Two of the xRNA nucleosides (i.e. rxA and rxU) are then converted to their corresponding phosphoramidites for use in automated RNA synthesis to synthesize various sets of xRNA-substituted siRNA strands for biophysical and biological studies. RNAi activity studies in HeLa cells using a firefly/Renilla luciferase dual reporter assay showed that xRNA substitutions in the antisense strand displayed poor RNAi activity in the middle of the sequence (positions 7-14) but were generally well tolerated near the 5'- and 3'-ends. Most significantly, single xRNA substitutions at the 3'-end showed RNAi activity that was more potent than that of unmodified siRNAs. Thermal denaturation studies revealed small changes in melting temperature (+1.4 to --5.0 °C); xRNA substitutions in the middle were found to be more thermodynamically destabilizing whereas the ends were shown to be stabilizing. Serum stability studies showed that xRNA-containing siRNAs have longer half-lives in human serum than unmodified siRNAs. Finally, xRNA-substituted siRNA strands and duplexes showed interesting position-dependent fluorescent properties, while CD spectroscopy experiments revealed that xRNA-substituted siRNAs does not greatly distort the native A-form helical structure of the duplexes. Taken together, the data demonstrate the utility of xRNA nucleobases as size-expanded mechanistic probes for RNAi research.
  • 2012
    Pratik Verma.
    Reductive activation of dioxygen by copper to generate potent oxidants for multi- electron organic transformations is exploited extensively in biological systems. This thesis focuses on two types of multi-electron oxidants: Cu2O2 complexes and copper complexes with redox-active ligands. The goal of this work is to identify the influence of nitrogen containing ancillary ligands on properties of dioxygen, semiquinone and phenoxyl radical complexes of copper. This work is aimed primarily at synthetic chemists interested in rational design of ligands for creating bio-inspired oxidants and oxidation catalysts. Chapter 1 of this thesis reports the identification of a Density Functional Theory (DFT) protocol for deriving structure-property relationships in Cu2O2 complexes. Chapter 2 of this thesis applies towards modeling electronic spectra, the DFT protocols that were validated in Chapter 1 for modeling thermodynamics. Chapter 3 of this thesis describes the properties and reactivity of Cu2O2 complex generated from a new hybrid permethylated-amine-guanidine ligand based on a 1,3- propanediamine backbone (2L). Chapter 4 of this thesis describes the characterization of an intermediate (C) that is observed in both phenol hydroxylation and catechol oxidation with the SP core supported by N1, N2-di-t-butylethane-1,2-diamine (DBED). Chapter 5 of this thesis describes the influence of sulfanyl substituents on the optical and redox properties of copper-bonded phenoxyls.
  • 2006 Springer
    K.-H. Hellwich, C.D. Siebert ; translated by Allan D. Dunn.
  • 2005 HighWire
    International Commission on Radiation Units and Measurements.
    Also available: Print – 2005
  • 2010
    John Vincent Mulcahy.
    Voltage-gated sodium ion channels are integral membrane proteins most commonly associated with the propagation of action potentials along electrically conducting cells. Nine distinct mammalian isoforms exist, which vary in their primary sequence, gating properties and tissue distribution. Efforts to deconvolute the physiological roles of each isoform through genetic methods, including knockout and gene silencing, are complicated by issues of redundancy and compensatory upregulation of related isoforms. Here we present new strategies and methods for the synthesis of a class of small molecule sodium channel inhibitors, the paralytic shellfish poisons. Methods for the construction of cyclic 5-membered guanidines from acyclic precursors through intramolecular C--H amination and a total synthesis of the paralytic shellfish poison (+)-gonyautoxin 3 are described. It is our vision that these developments will ultimately lead to new small molecule probes designed to help answer fundamental questions regarding sodium ion channel structure and diversity.
  • 2006 CRCnetBASE
    edited by Ryan Richards.
  • 2005 CRCnetBASE
    edited by Pankaj Vadgama.
  • v. 78, 80, 89, 93, 95-96, 100, 102-103, 105, 108-117, 119-, 1999- CRCnetBase
    Schick, Martin J.
  • 2008 Springer
    Kailash C. Khulbe, C.Y. Feng, Takeshi Matsuura.
  • 2012
    Elizabeth Josephine Beans.
    The theme of this work is to utilize hypothesis driven synthetic manipulation to enhance our understanding of the biological effects of prostratin and its highly potent analogs, and to utilize this understanding for the improvement of the therapeutic properties thereof. Prostratin, a natural product activator of protein kinase C (PKC), is a molecule of interest for targeting latent HIV, the primary obstacle to HIV eradication in infected individuals on effective highly active antiretroviral therapy. Chapter one describes the current state of the HIV pandemic, therapeutic strategies, prospects for a cure, and clinical studies toward immune activation therapy. Chapter two is a seminal and complete analysis of the biological effects of prostratin, a natural product candidate for immune activation therapy. Chapter three presents the design, synthesis, and evaluation of highly potent analogs of prostratin via an efficient semi-synthetic route. Chapter four presents the design and synthesis of isotopically labeled prostratin analogs to be utilized in solid-state NMR studies probing the active conformation of the PKC/activator complex in its membrane associated state. Chapter five presents the design, synthesis, and evaluation of prodrugs of prostratin and prostratin analogs for the optimization of pharmacologic properties.
  • An online journal and ebook service of the Thieme Publishing Group. The ebook package is also called Thieme Clinical Collections.
  • 2008 CRCnetBASE
    [edited by] Monika Waksmundzka-Hajnos, Joseph Sherma, Teresa Kowalska.
  • 2005- Wiley
    Ullmann, Fritz.
    Covers science and technology in all areas of industrial chemistry, containing nearly 1000 major articles with more than 16 million words, nearly 10,000 tables, 30,000 figures, and literature sources and cross-references. It also includes full text index, author index, CAS registry number index, and keyword index.
  • 2008 CRCnetBASE
    Hugh Cartwright ; chapter 10, Evolvable developmental systems, contributed by Nawwaf Kharma.
  • 2010
    Justin David Litchfield.
    Several methods of examining the structure and function of voltage-gated ion channels are described. The first part of this work involves synthetic small molecules based on the structure of (+)-saxitoxin, a marine neurotoxin. (+)-saxitoxin interacts with the pore of the voltage-gated sodium (NaV ) channel to prevent the passage of ions. A scaffold was designed to be modular, synthetically facile, and contain the functionality that had been implicated in the previous literature. Several members of this family of molecules were produced, and they were assayed for occlusion of sodium current (INa). The second part of this work examines the gating kinetics of voltage-gated potassium (KV) channels. 6-bromo-mercaptotryptamine (BrMT) is a marine neurotoxin that has been shown to alter the gating kinetics of KV channels. Specifically, BrMT affects the early, typically independent steps of KV gating by stabilizing the resting state of some number of the subunits. A family of small molecules was designed and synthesized that would examine the functional effects of different parts of the BrMT molecule. BrMT is a dimer containing three key functional groups: a halogenated indole, a pendant ethyl-amine, and a disulfide linker. Variance at all these positions was examined, and each had different effects. Notably, one of the variants, in which the disulfide linker was substituted for an oxy-bismethyl ether linker, affects KV gating in a different way from BrMT. Alternate models of gating in the presence of this novel analog are discussed.
  • 2011
    Mari Iwamoto.
    The ability to make specific perturbations to biological molecules in a cell or organism is a central experimental strategy in modern research biology. Chemical approaches to probe biological function have greatly contributed to the understanding of protein functions. While small-molecule inhibitors offer rapid and reversible control of protein functions, identification and development of specific inhibitors for every protein of interest remains a challenge. In the past decade, numerous technologies have been developed that combine genetic with chemical methods to create conditional protein control systems with impeccable specificity. These systems include inducible protein localization using chemical inducer of dimerization, such as rapamycin, and inducible protein stabilization system such as our destabilizing domain (DD) technology previously developed by L. Banaszynski. Highly specific, high-affinity protein-ligand interactions are key to their effectiveness. In this thesis, three technologies that utilize highly specific protein-ligand interactions are discussed. The first chapter of this thesis focuses on the development of a general technique in which the stability of a specific protein is regulated by a cell-permeable small molecule. Mutants of E. coli dihydrofolate reductase (ecDHFR) were engineered to have ligand-dependent stability, and when this destabilizing domain is fused to a protein of interest, the instability is conferred to the fused protein resulting in rapid degradation of the entire fusion protein. A small-molecule ligand trimethoprim (TMP) stabilized the destabilizing domain in a rapid, reversible and dose-dependent manner, and protein levels in the absence of TMP were barely detectable. The ability of TMP to cross the blood-brain barrier enabled the tunable regulation of YFP expressed rat striatum. The second chapter of this thesis describes the development of a technique in which a protein of interest is degraded in the presence of a ligand. In this system, we regulated the stability of a receptor protein of an E3 ligase complex using the previously developed destabilizing domains. A DD-fused receptor protein cannot recruit the substrate to the E3 ubiquitin ligase in the absence of ligand. Upon addition of ligand, the receptor protein is stabilized and can successfully promote ubiquitination and degradation of the substrate protein. We used HIV-1 Vif protein, a receptor protein of the Cul5 E3 ligase complex, and its substrate, human APOBEC3G. We were able to induce degradation of GFP fused APOBEC3G upon addition of ligand. Degradation of GFP occurred rapidly, tunably, and reversibly. The advantage of this system over the DD technology is that it does not require continuous administration of the ligand until the desired experimental window and is thus better suited for in vivo applications. By limiting the dosage to only during the knockout window, the cost of dosing is dramatically decreased and side effects from long-term administration of ligand can be minimized. The third and last chapter of this thesis describes an attempt to develop a new approach to induce genome modification at a specific site with high efficiency in mammalian cell lines. While there are several successful nuclease-based gene-targeting approaches that exist today, these technologies require extensive engineering and screening to isolate efficient and specific nucleases that bind to the target sites. Our strategy was to simplify the design of DNA targeting domains by using an oligonucleotide analogue, peptide nucleic acid (PNA). PNAs incorporate DNA bases on peptide backbones and make base-specific contacts with the target DNA site. The PNA domain is coupled to TMP, which then allows recruitment of the nuclease domain fused to ecDHFR. The nuclease domain is made up of a single-chain, pseudohomodimer FokI catalytic domain that non-specifically cleaves the DNA. We could not produce any recombination activity in cell. However, in vivo experiments revealed successful target DNA binding by the PNA, as well as TMP-PNA/ecDHFR-FokI binding.
  • 2012 Springer Protocols
    edited by Emilio Badoer.
    Multiple immunohistochemical labelling of peripheral neurons / Ian L. Gibbins -- Combined in situ hybridization and immunohistochemistry in rat brain tissue using digoxigenin-labeled riboprobes / Natasha N. Kumar, Belinda R. Bowman, and Ann K. Goodchild -- In situ hybridization within the CNS tissue : combining in situ hybridization with immunofluorescence / Dominic Bastien and Steve Lacroix -- Visualizing GABA[subscriptβ] receptor internalization and intracellular trafficking / Paola Ramoino [and others] -- Using total internal reflection fluorescence microscopy (TIRFM) to visualise insulin action / James G. Burchfield, Jamie A. Lopez, and William E. Hughes -- Live-cell quantification of mitochondrial functional parameters / Marco Nooteboom [and others] -- Functional imaging using two-photon microscopy in living tissue / Ivo Vanzetta [and others] -- Calcium imaging techniques in vitro to explore the role of dendrites in signaling physiological action potential patterns / Audrey Bonnan, Benjamin Grewe, and Andreas Frick -- Juxtacellular labeling in combination with other histological techniques to determine phenotype of physiologically identified neurons / Ruth L. Stornetta -- Visualization of activated neurons involved in endocrine and dietary pathways using GFP-expressing mice / Rim Hassouna [and others] -- Use and visualization of neuroanatomical viral transneuronal tracers / J. Patrick Card and Lynn W. Enquist -- Visualisation of thermal changes in freely moving animals / Daniel M.L. Vianna and Pascal Carrive -- Perfusion magnetic resonance imaging quantification in the brain / Fernando Calamante.
  • 2007 Wiley
    Albrecht Messerschmidt.
    Part I. Principles and Methods -- Chapter 1. Introduction, p. 1-22 -- Chapter 2. Experimental Techniques, p. 23-44 -- Chapter 3. Principles of X-Ray Diffraction by a Crystal, p. 45-79 -- Chapter 4. Diffraction Data Evaluation, p. 81-97 -- Chapter 5. Methods for Solving the Phase Problem, p. 99-139 -- Chapter 6. Phase Improvement by Density Modification and Phase Combination, p. 141-156 -- Chapter 7. Model Building and Refinement, p. 157-185 -- Chapter 8. Crystal Structure Determination of the Time-Course of Reactions and of Unstable Species, p. 187-202 -- Chapter 9. Structural Genomics, p. 203-220 -- Part II. Practical Examples -- Chapter 10. Data Evaluation, p. 223-238 -- Chapter 11. Determination of Anomalous Scatterer or Heavy Atom Positions, p. 239-251 -- Chapter 12. MIRAS and MAD Phasing with the Program SHARP, p. 253-259 -- Chapter 13. Molecular Replacement, p. 261-266 -- Chapter 14. Averaging about Non-Crystallographic Symmetry (NCS) for 4-BUDH, p. 267-275 -- Chapter 15. Model Building and More, p. 277-291

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