gebhart/patrepeval huggingface dataset:
Synthesis and spectroscopy of membrane receptor proteins (1992)

The high-affinity receptor for IgE is a tetrameric complex of subunits of the type alpha beta gamma 2. We report here conformational studies of the intact gamma subunit in trifluoroethanol and water/liposomes by circular dichroism and Fourier-transform infrared (FTIR) spectroscopy. In trifluoroethanol, the FTIR amide I' frequencies were consistent with two predominant conformational components, the beta-turn and alpha-helix, whilst in liposomes consisting of D2O and dimyristoylglycerophosphocholine (Myr2GroPCho), three components were observed. The third component present may contain some left-handed extended helix. Spectral simulation was carried out to demonstrate that the CD spectra were consistent with the component conformations identified from FTIR spectroscopy. The stimulated CD spectra were in excellent agreement with the experimental spectra. The intact gamma subunit conformation in trifluoroethanol was shown to possess 72% alpha-helical and 28% beta-turn conformations. In water/Myr2GroPCho liposomes the percentage of each conformational component present is 37%, 38% and 25% for the alpha-helix, beta-turn and extended structures, respectively. Assuming that the transmembrane fragment was alpha-helical, an excellent correlation was found between this derived alpha-helical content in water/liposomes (37%) and from hydrophobicity plots where the percentage of amino acids in the transmembrane domain is predicted by others to be 34%. It is suggested that the beta-turn detected by CD and FTIR was attributable to a 3(10) helix rather than a type I or type III reverse turn.
Solution and Solid-State Characterization of Highly Rigid, Eight-Coordinate Lanthanide(III) Complexes of a Macrocyclic Tetrabenzylphosphinate (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSolution and Solid-State Characterization of Highly Rigid, Eight-Coordinate Lanthanide(III) Complexes of a Macrocyclic TetrabenzylphosphinateSilvio Aime, Andrei S. Batsanov, Mauro Botta, Judith A. K. Howard, David Parker, Kanthi Senanayake, and Gareth WilliamsCite this: Inorg. Chem. 1994, 33, 21, 4696–4706Publication Date (Print):October 1, 1994Publication History Published online1 May 2002Published inissue 1 October 1994https://pubs.acs.org/doi/10.1021/ic00099a020https://doi.org/10.1021/ic00099a020research-articleACS PublicationsRequest reuse permissionsArticle Views502Altmetric-Citations110LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Linking Brain Imaging and Genomics in the Study of Alzheimer's Disease and Aging (2007)

My colleagues and I have been using positron emission tomography (PET) and magnetic resonance imaging (MRI) to detect and track the brain changes associated with Alzheimer's disease (AD) and normal brain aging in cognitively normal persons with two copies, one copy, and no copies of the apolipoprotein E (APOE) epsilon4 allele, a common AD susceptibility gene. In this review article, I consider how brain imaging techniques could be used to evaluate putative AD prevention therapies in cognitively normal APOE epsilon4 carriers and putative age-modifying therapies in cognitively normal APOE epsilon4 noncarriers, how they could help investigate the individual and aggregate effects of putative AD risk modifiers, and how they could help guide the investigation of a molecular mechanism associated with AD vulnerability and normal neurological aging. I suggest how high-resolution genome-wide genetic and transcriptomic studies could further help in the scientific understanding of AD, aging, and other common and genetically complex phenotypes, such as variation in normal human memory performance, and in the discovery and evaluation of promising treatments for these phenotypes. Finally, I illustrate the push-pull relationship between brain imaging, genomics research, and other neuroscientific research in the study of AD and aging.
Superfast phase-shifting method for 3-D shape measurement (2010)

Recently introduced DLP Discovery technology allows for tens of kHz binary image switching, which has great potential for superfast 3-D shape measurement. This paper presents a system that realizes 3-D shape measurement by using a DLP Discovery technology to switch binary structured patterns at very high frame rates. The sinusoidal fringe patterns are generated by properly defocusing the projector. Combining this approach with a phase-shifting method, we achieve an unprecedented rate for 3-D shape measurement: 667 Hz. This technology can be applied to numerous applications including medical science, biometrics, and entertainment.
POTENTIAL ROLE OF THE PEROXYNITRITE-POLY(ADP-RIBOSE) SYNTHETASE PATHWAY IN A RAT MODEL OF SEVERE HEMORRHAGIC SHOCK (1998)

Peroxynitrite (a potent oxidant produced by nitric oxide and superoxide) and hydroxyl radical, reactive oxidants produced during hemorrhagic shock, are potent triggers of DNA single-strand breakage. DNA injury triggers the activation of the nuclear enzyme poly(ADP-ribose) synthetase (PARS), which contributes to cellular injury. Hemorrhagic shock is associated with early vasomotor paralysis as well as with early derangements in the cellular metabolic status. Here we have tested whether activation of PARS contributes to the vasodilatation and early mortality in a rat model of severe hemorrhagic shock. In anesthetized rats hemorrhaged to a mean arterial blood pressure of 35 mmHg, pretreatment with the PARS inhibitor 5-iodo-6-amino-1,2-benzopyrone significantly improved survival rate. Furthermore, an inhibitor of nitric oxide biosynthesis (NG-methyl-L-arginine) and the cell-permeable superoxide dismutase mimetic Mn(III)tetrakis(4-benzoic acid) porphyrin also offered a significant protection in terms of hypotension and acute mortality. However, the selective inhibitor of the inducible nitric oxide synthase, mercaptoethylguanidine, failed to affect blood pressure or mortality. The present data suggest that PARS activation plays a role in the pathophysiology of hemorrhagic shock. Early production of peroxynitrite (produced by nitric oxide from constitutive nitric oxide synthase) and hydroxyl radical may induce DNA single-strand breakage, which is the immediate trigger of PARS activation.
Architecture Implementation Using the Machine Description Language LISA (2002)

The development of application specific instruction set processors comprises several design phases: architecture exploration, software tools design, system verification and design implementation. The LISA processor design platform (LPDP) based on machine descriptions in the LISA language provides one common environment for these design phases. Required software tools for architecture exploration and application development can be generated from one sole specification. This paper focuses on the implementation phase and the generation of synthesizable HDL code from a LISA model. The derivation of the architectural structure, decoder and even approaches for the implementation of the data path are presented. Moreover the synthesis results of a generated and a handwritten implementation of a low-power DVB-T post processing unit are compared.
Antioxidant and redox regulation of gene transcription (1996)

Reactive oxygen species (ROS) are implicated in the pathogenesis of a wide variety of human diseases. Recent evidence suggests that at moderately high concentrations, certain forms of ROS such as H202 may act as signal transduction messengers. To develop a better understanding of the exact mechanisms that underlie ROS-dependent disorders in biological systems, recent studies have investigated the regulation of gene expression by oxidants, antioxidants, and other determinants of the intracellular reduction-oxidation (redox) state. At least two well-defined transcription factors, nuclear factor (NF) kappa B and activator protein (AP) -1 have been identified to be regulated by the intracellular redox state. The regulation of gene expression by oxidants, antioxidants, and the redox state has emerged as a novel subdiscipline in molecular biology that has promising therapeutic implications. Binding sites of the redox-regulated transcription factors NF-kappa B and AP-1 are located in the promoter region of a large variety of genes that are directly involved in the pathogenesis of diseases, e.g., AIDS, cancer, atherosclerosis and diabetic complications. Biochemical and clinical studies have indicated that antioxidant therapy may be useful in the treatment of disease. Critical steps in the signal transduction cascade are sensitive to oxidants and antioxidants. Many basic events of cell regulation such as protein phosphorylation and binding of transcription factors to consensus sites on DNA are driven by physiological oxidant-antioxidant homeostasis, especially by the thiol-disulfide balance. Endogenous glutathione and thioredoxin systems, and the exogenous lipoate-dihydrolipoate couple may therefore be considered to be effective regulators of redox-sensitive gene expression. The efficacy of different antioxidants to favorably influence the molecular mechanisms implicated in human disease should be a critical determinant of its selection for clinical studies.
Libraries against libraries for combinatorial selection of replicating antigen–antibody pairs (2009)

Antibodies are among the most highly selective tight-binding ligands for proteins. Because the human genome project has deciphered the proteome, there is an opportunity to use combinatorial antibody libraries to select high-affinity antibodies to every protein encoded by the genome. However, this is a large task because the selection formats used today for combinatorial antibody libraries are geared toward generating antibodies to one antigen at a time. Here, we describe a method that accelerates the identification of antibodies to a multitude of antigens simultaneously by matching combinatorial antibody libraries against eukaryotic antigen libraries so that replication-competent cognate antigen-antibody pairs can be directly selected. Phage and yeast display systems are used because they each link genotype to phenotype and can be replicated individually. When combined with cell sorting, the two libraries can be selected against each other for recovery of cognate antigen-antibody clones in a single experiment.
Characterization of the Antimonial Antileishmanial Agent Meglumine Antimonate (Glucantime) (1998)

Meglumine antimonate (Glucantime), a drug of choice for the treatment of leishmaniasis, is produced by the reaction of pentavalent antimony with N-methyl-D-glucamine, a carbohydrate derivative. We investigated the structure and composition of meglumine antimonate, which remain poorly understood, despite 50 years of use. Measurement of the antimony content of meglumine antimonate powder indicated a 1:1.37 molar ratio of antimony to N-methyl-D-glucamine. Osmolality measurements performed with meglumine antimonate solutions demonstrated an average of 1.43 antimony atoms per molecule of meglumine antimonate. The osmolality of a 1:10 dilution of stock meglumine antimonate increased by 45% over 8 days, suggesting hydrolysis to less complex species. A comparison of the proton nuclear magnetic resonance spectra of N-methyl-D-glucamine and meglumine antimonate revealed an increase in complexity in the latter but with all of the resonances of the former still being evident, consistent with the presence of coordination complexes between antimony and each of the N-methyl-D-glucamine hydroxyls. Fast atom bombardment and electrospray ionization mass spectrometry coupled with several derivatization procedures provided evidence that up to four N-methyl-D-glucamine hydroxyls are coordinated with each antimony. A series of oligomers were observed. The major moiety has a molecular mass of 507 atomic mass units and consists of NMG-Sb-NMG, where Sb represents antimony and NMG represents N-methyl-D-glucamine. Additional species containing up to four antimony atoms and five N-methyl-D-glucamine moieties and corresponding to the general form (NMG-Sb)n-NMG are also present. These results suggest that this agent is a complex mixture that exists in equilibrium in aqueous solution.
Differentiated Thyroid Carcinoma After 131 I-MIBG Treatment for Neuroblastoma During Childhood: Description of the First Two Cases (2012)

Both these cases of DTC after (131)I-MIBG for childhood NBL underline the importance of adequate thyroid protection against radiation exposure during treatment for NBL. Children who have been treated with (131)I-MIBG should be given life-long follow-up, not only with regard to thyroid function, but also with surveillance for the development of thyroid nodules and thyroid cancer.
Force Regulation of Ankle Extensor Muscle Activity in Freely Walking Cats (2008)

To gain insight into the relative importance of force feedback to ongoing ankle extensor activity during walking in the conscious cat, we isolated the medial gastrocnemius muscle (MG) by denervating the other ankle extensors and measured the magnitude of its activity at different muscle lengths, velocities, and forces accomplished by having the animals walk up and down a sloped pegway. Mathematical models of proprioceptor dynamics predicted afferent activity and revealed that the changes in muscle activity under our experimental conditions were strongly correlated with Ib activity and not consistently associated with changes in Ia or group II activity. This allowed us to determine the gains within the force feedback pathway using a simple model of the neuromuscular system and the measured relationship between MG activity and force. Loop gain increased with muscle length due to the intrinsic force-length property of muscle. The gain of the pathway that converts muscle force to motoneuron depolarization was independent of length. To better test for a causal relationship between modulation of force feedback and changes in muscle activity, a second set of experiments was performed in which the MG muscle was perturbed during ground contact of the hind foot by dropping or lifting the peg underfoot. Collectively, these investigations support a causal role for force feedback and indicate that about 30% of the total muscle activity is due to force feedback during level walking. Force feedback's role increases during upslope walking and decreases during downslope walking, providing a simple mechanism for compensating for changes in terrain.
Crystal Structure of the T315I Mutant of Abl Kinase (2007)

Imatinib (Gleevec) is currently the frontline therapy for chronic myeloid leukemia (CML), a disease characterized by the presence of a constitutively activated chimeric tyrosine kinase protein Bcr-AbI. However, drug resistance often occurs at later stages of the disease, principally because of the occurrence of mutations in the kinase domain. Second generation Bcr-AbI inhibitors, such as dasatinib and nilotinib are capable of inhibiting many imatinib-resistant forms of the kinase but not the form in which threonine is mutated to isoleucine at the gatekeeper position (T315I). In this study, we present the crystal structure of the kinase domain of the c-AbI T315I mutant, as well as the wild-type form, in complex with a pyrrolopyridine inhibitor, PPY-A. The side chain of Ile315 is accommodated in the AbI T315I mutant structure without large conformational changes proximal to the site of mutation. In contrast to other inhibitors, such as imatinib and dasatinib, PPY-A does not occupy the hydrophobic pocket behind the gatekeeper residue. This binding mode, coupled with augmented contacts with the glycine-rich loop, appears to be critical for its ability to override the T315I mutation. The data presented here may provide structural guidance for the design of clinically useful inhibitors of Bcr-AbI T315I.
SMNΔ7, the major product of the centromeric survival motor neuron (SMN2) gene, extends survival in mice with spinal muscular atrophy and associates with full-length SMN (2005)

Spinal muscular atrophy (SMA) is an autosomal recessive disorder in humans which results in the loss of motor neurons. It is caused by reduced levels of the survival motor neuron (SMN) protein as a result of loss or mutation of the SMN1 gene. SMN is encoded by two genes, SMN1 and SMN2, which essentially differ by a single nucleotide in exon 7. As a result, the majority of the transcript from SMN2 lacks exon 7 (SMNDelta7). SMNDelta7 may be toxic and detrimental in SMA, which, if true, could lead to adverse effects with drugs that stimulate expression of SMN2. To determine the role of SMNDelta7 in SMA, we created transgenic mice expressing SMNDelta7 and crossed them onto a severe SMA background. We found that the SMNDelta7 is not detrimental in that it extends survival of SMA mice from 5.2 to 13.3 days. Unlike mice with selective deletion of SMN exon 7 in muscle, these mice with a small amount of full-length SMN (FL-SMN) did not show a dystrophic phenotype. This indicates that low levels of FL-SMN as found in SMA patients and absence of FL-SMN in muscle tissue have different effects and raises the question of the importance of high SMN levels in muscle in the presentation of SMA. SMN and SMNDelta7 can associate with each other and we suggest that this association stabilizes SMNDelta7 protein turnover and ameliorates the SMA phenotype by increasing the amount of oligomeric SMN. The increased survival of the SMNDelta7 SMA mice we report will facilitate testing of therapies and indicates the importance of considering co-complexes of SMN and SMNDelta7 when analyzing SMN function.
A human placenta-specific ATP-binding cassette gene (ABCP) on chromosome 4q22 that is involved in multidrug resistance. (1998)

We characterized a new human ATP-binding cassette (ABC) transporter gene that is highly expressed in the placenta. The gene, ABCP, produces two transcripts that differ at the 5' end and encode the same 655-amino acid protein. The predicted protein is closely related to the Drosophila white and yeast ADP1 genes and is a member of a subfamily that includes several multidrug resistance transporters. ABCP, white, and ADP1 all have a single ATP-binding domain at the NH2 terminus and a single COOH-terminal set of transmembrane segments. ABCP maps to human chromosome 4q22, between the markers D4S2462 and D4S1557, and the murine gene (Abcp) is located on chromosome 6 28-29 cM from the centromere. ABCP defines a new syntenic segment between human chromosome 4 and mouse chromosome 6. The abundant expression of this gene in the placenta suggests that the protein product has an important role in transport of specific molecule(s) into or out of this tissue.
Pre-Clinical Evaluation of a 213Bi-Labeled 2556 Antibody to HIV-1 gp41 Glycoprotein in HIV-1 Mouse Models as a Reagent for HIV Eradication (2012)

We describe the preclinical development of a novel radiolabeled mAb reagent that could potentially be part of an HIV eradication strategy that is ready for translation into the clinic as the next step in its development. As viral antigens are very different from "self" human antigens - this approach promises high selectivity, increased efficacy and low toxicity, especially in comparison to immunotoxins.
Detection sensitivity of genetic field effect transistor combined with charged nanoparticle-DNA conjugate (2006)

We demonstrated the effectiveness of introduction of charged nanoparticle-DNA conjugate for detection sensitivity of the genetic field effect transistor (FET), of which the principle is based on the potentiometric detection of charge density change on the gate surface. The large amount of negative charges on the gate insulator induced strongly the electrostatic interaction with electrons in silicon crystal by field effect resulting in the bigger shift of threshold voltage. The genetic FET platform combined with the charged nanoparticle-DNA conjugate is suitable for a simple, sensitive, accurate and inexpensive system for DNA analyses in clinical diagnostics
Wavelength-division multi/demultiplexer utilizing optically active crystals (1990)

A wavelength-division multi/demultiplexer (W-MUX/DEMUX) utilizing optically active crystals is proposed and studied. It is shown that using two or more optically active crystals having different rotary powers and dispersions is effective for providing design freedom and for easy assembly of the W-MUX/DEMUX. A design for a two-wavelength W-MUX/DEMUX is also discussed. Based on this design, a W-MUX/DEMUX that multiplexes or demultiplexes light with wavelengths of 0.8 and 1.1 mu m was fabricated. The insertion losses are 1.6 and 3.1 dB at wavelengths of 0.8 and 1.1 mu m, respectively. Crosstalk attenuation of 13 dB or more is obtained at these wavelengths.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Pretreatment with Rituximab Does Not Inhibit the Human Immune Response against the Immunogenic Protein LMB-1 (2004)

Abstract Purpose: Rituximab, a humanized monoclonal antibody directed to the CD20 antigen present on B lymphocytes, could potentially abrogate the humoral immune response to murine monoclonal antibodies or immunotoxins by depleting antibody-producing B cells. Experimental Design: A Phase II study of LMB-1, an immunotoxin targeting the Lewis Y tumor antigen, in combination with rituximab was conducted to test the hypothesis that rituximab could abolish or diminish the development of human antibodies to LMB-1. Five patients were treated in this study and received 375 mg/m2 rituximab on days 1 and 7 followed by 45 μg/kg/day LMB-1 on days 10, 12, and 14. The development of human antibodies against LMB-1 was detected using a serum neutralization and ELISA. Results: All five of the patients had a total suppression of circulating CD20/CD19 B-cell population before the administration of the first dose of the immunotoxin. Before rituximab treatment, the mean percentage of CD20/CD19-positive B cells in the five treated patients was 19.8% (range, 4.5–29.8%) of the total peripheral lymphocytes. After two doses of rituximab, CD20/CD19-positive B lymphocytes constituted ≤0.1% of the total peripheral lymphocytes. Despite absent circulating antibody-producing B cells, before and during LMB-1 treatment, all of the patients developed neutralizing antibodies to the immunotoxin by day 21 of drug administration, which prevented retreatment. Conclusions: Even though rituximab caused complete depletion of circulating CD20/CD19-positive B cells, it had no effect in suppressing the human antibody response to LMB-1 and may be of limited utility in suppressing human antibody responses to other immunogenic proteins.