gebhart/patrepeval huggingface dataset:
Heterofullerenes (2006)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHeterofullerenesOtto Vostrowsky and Andreas HirschView Author Information Institut für Organische Chemie, Universität Erlangen-Nürnberg, Henkestrasse 42, 91054 Erlangen, Germany Cite this: Chem. Rev. 2006, 106, 12, 5191–5207Publication Date (Web):November 3, 2006Publication History Received11 April 2006Published online3 November 2006Published inissue 1 December 2006https://pubs.acs.org/doi/10.1021/cr050561ehttps://doi.org/10.1021/cr050561eresearch-articleACS PublicationsCopyright © 2006 American Chemical SocietyRequest reuse permissionsArticle Views3346Altmetric-Citations215LEARN 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-Alertsclose SUBJECTS:Carbon,Carbon nanomaterials,Molecular structure,Nanospheres,Oligomers Get e-Alerts
Numerical study of spot-size expanders for an efficient OEIC to SMF coupling (1998)

Different types of spot-size converters are studied numerically, and their coupling loss and reflection properties are discussed in detail. The rigorous vector finite-element method is used to calculate the modal propagation properties and the least-squares boundary residual method is employed to calculate the coupling loss, reflection coefficient, and the alignment tolerances of the devices. It has also been observed that the reflection coefficient reaches a minimum when the mode confinement is at its maximum.
Contribution of a single heavy chain residue to specificity of an anti‐digoxin monoclonal antibody (1994)

Two distinct spontaneous variants of the murine anti-digoxin hybridoma 26-10 were isolated by fluorescence-activated cell sorting for reduced affinity of surface antibody for antigen. Nucleotide and partial amino acid sequencing of the variant antibody variable regions revealed that 1 variant had a single amino acid substitution: Lys for Asn at heavy chain position 35. The second variant antibody had 2 heavy chain substitutions: Tyr for Asn at position 35, and Met for Arg at position 38. Mutagenesis experiments confirmed that the position 35 substitutions were solely responsible for the markedly reduced affinity of both variant antibodies. Several mutants with more conservative position 35 substitutions were engineered to ascertain the contribution of Asn 35 to the binding of digoxin to antibody 26-10. Replacement of Asn with Gln reduced affinity for digoxin 10-fold relative to the wild-type antibody, but maintained wild-type fine specificity for cardiac glycoside analogues. All other substitutions (Val, Thr, Leu, Ala, and Asp) reduced affinity by at least 90-fold and caused distinct shifts in fine specificity. The Ala mutant demonstrated greatly increased relative affinities for 16-acetylated haptens and haptens with a saturated lactone. The X-ray crystal structure of the 26-10 Fab in complex with digoxin (Jeffrey PD et al., 1993, Proc Natl Acad Sci USA 90:10310-10314) reveals that the position 35 Asn contacts hapten and forms hydrogen bonds with 2 other contact residues. The reductions in affinity of the position 35 mutants for digoxin are greater than expected based upon the small hapten contact area provided by the wild-type Asn. We therefore performed molecular modeling experiments which suggested that substitution of Gln or Asp can maintain these hydrogen bonds whereas the other substituted side chains cannot. The altered binding of the Asp mutant may be due to the introduction of a negative charge. The similarities in binding of the wild-type and Gln-mutant antibodies, however, suggest that these hydrogen bonds are important for maintaining the architecture of the binding site and therefore the affinity and specificity of this antibody. The Ala mutant eliminates the wild-type hydrogen bonding, and molecular modeling suggests that the reduced side-chain volume also provides space that can accommodate a congener with a 16-acetyl group or saturated lactone, accounting for the altered fine specificity of this antibody.
Hybrid cytokines as hematopoietic growth factors (1991)

A large body of in vitro and in vivo data suggests that combinations of cytokines provide the most effective mechanism for stimulating multilineage acceleration of hematopoiesis. Creation of a granulocyte-macrophage colony-stimulating factor (GM-CSF)/interleukin 3 (IL-3) fusion protein has yielded a single therapeutic which has enhanced biological activity in comparison to the individual cytokines from which it is composed. In vivo studies with this fusion protein (PIXY321) suggest that it may provide a means to accelerate both neutrophil and platelet recovery in clinical settings in which hematopoiesis is suppressed. The biology of PIXY321 and the potential for other fusion proteins is discussed.
Inhibition of hepatitis B virus by the CRISPR/Cas9 system via targeting the conserved regions of the viral genome (2015)

Hepatitis B virus (HBV) remains a global health threat as chronic HBV infection may lead to liver cirrhosis or cancer. Current antiviral therapies with nucleoside analogues can inhibit the replication of HBV, but do not disrupt the already existing HBV covalently closed circular DNA. The newly developed CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated 9) system is a powerful tool to target cellular genome DNA for gene editing. In order to investigate the possibility of using the CRISPR/Cas9 system to disrupt the HBV DNA templates, we designed eight guide RNAs (gRNAs) that targeted the conserved regions of different HBV genotypes, which could significantly inhibit HBV replication both in vitro and in vivo. Moreover, the HBV-specific gRNA/Cas9 system could inhibit the replication of HBV of different genotypes in cells, and the viral DNA was significantly reduced by a single gRNA/Cas9 system and cleared by a combination of different gRNA/Cas9 systems.
A Conserved Element in the Serine Protease Domain of Complement Factor B (1998)

Factor B and C2 are serine proteases that carry the catalytic sites of the complement C3 and C5 convertases. Their protease domains are activated by conformational changes that occur during convertase assembly and are deactivated upon convertase dissociation. Factor B and C2 share an 8-amino acid conserved sequence near their serine protease termini that is not seen in other serine proteases. To determine its importance, 24 factor B mutants were generated, each with a single amino acid substitution in this region. Whereas most mutants were functionally neutral, all five different substitutions of aspartic acid 715 and one phenylalanine 716 substitution severely reduced hemolytic activity. Several aspartic acid 715 mutants permitted the steps of convertase assembly including C3b-dependent factor D-mediated cleavage and activation of the high affinity C3b-binding site, but the resulting complexes did not cleave C3. Given that factor B and C2 share the same biological substrates and that part of the trypsin-like substrate specificity region is not apparent in either protein, we propose that the conserved region plays a critical role in the conformational regulation of the catalytic site and could offer a highly specific target for the therapeutic inhibition of complement.
The potential of interleukin 12 inhibition in the treatment of psoriasis. (2005)

Interleukin 12 (IL-12) is an important cytokine produced by a variety of immune effector cells that leads to a type 1 helper T cell (Th1) response. IL-12 also directs T cells to the skin via induction of cutaneous lymphocyte antigen (CLA) expression. In this article we report the current understanding of the immunobiology of IL-12, reviewing its structure, receptor, and function. We also discuss the role of IL-12 in the pathogenesis of psoriasis. Some effective conventional psoriasis treatments alter IL-12 levels. Importantly, specific antibodies directed against IL-12 may prove useful against psoriasis but may also act by targeting IL-23 in addition to IL-12.
Molecular cloning and characterization of PEA3, a new member of the Ets oncogene family that is differentially expressed in mouse embryonic cells. (1992)

The PEA3 motif, first recognized in the polyomavirus enhancer, is an oncogene, serum growth factor, and phorbol ester-responsive element. An activity capable of binding to this sequence, termed PEA3 (polyomavirus enhancer activator 3), was identified in mouse 3T6 cell nuclear extracts. We have cloned cDNAs that encode PEA3 from a mouse FM3A cell cDNA library. A continuous open reading frame in the longest cDNA predicts a 555-amino-acid protein with a calculated molecular mass of 61 kD. Recombinant PEA3 binds to DNA with the same sequence specificity as that endogenous to FM3A cells and activates transcription through the PEA3 motif in HeLa cells. Deletion mapping of the protein revealed that the DNA-binding domain is located within a stretch of 102 amino acids near the carboxyl terminus. This region shares extensive sequence similarity with the ETS domain, a conserved protein sequence common to all ets gene family members. PEA3 is encoded by a 2.4-kb mRNA that is expressed to differing extents in fibroblastic and epithelial cell lines but not in hematopoietic cell lines. In the mouse, PEA3 expression is highly restricted; only the epididymis and the brain contain readily detectable amounts of its mRNA. Interestingly, the amount of PEA3 mRNA is down-regulated during retinoic acid-induced differentiation of mouse embryonic cell lines. These findings suggest that PEA3 plays a regulatory role during mouse embryogenesis.
Antituberculosis treatment-induced hepatotoxicity: role of predictive factors (1995)

Antituberculosis drug-induced hepatotoxicity is quite common. However, factors predicting its development are still controversial. The objective of the present study was to evaluate the role of certain factors (age and sex of the patient, alcoholism, chronic liver disease, hepatitis B virus carrier status, acetylator status, nutritional status and antituberculosis treatment (ATT) regimen) in predicting the development of ATT-induced hepatitis. In a case-control study, 60 consecutive patients with evidence of ATT-induced hepatitis were studied to assess the possible association of the above-mentioned factors with ATT-induced hepatitis. Body mass index was found to be significantly lower in ATT-induced hepatitis patients (17.2 +/- 2.7) than in controls (19.5 +/- 3.3) (p < 0.05). Pyrazinamide was used in addition to isoniazid and rifampicin in a significantly higher percentage of patients in the ATT-induced hepatitis group (70%) as compared with those in the control group (42%). No significant differences were observed between the two groups with regard to the rest of the parameters.
A liquid-crystal phase modulator for large-screen projection (1989)

The substitution of a liquid-crystal phase modulator for the electrically deformable oil film used for image generation in some large-screen projectors is studied. The liquid crystal causes a voltage-dependent phase shift to the incident light, which is converted into amplitude-modulated light by means of a schlieren optical system. A cell configuration in which the phase shift is about equal for both polarization directions, so that no polarizers are necessary and therefore optical efficiency can be increased, was found. The diffraction properties of the resulting rectangular phase grid were investigated. When used with a thin-film transistor array or a wafer-scale MOS transistor array as drivers, a gray scale projection is possible.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Control of interspecies electron transfer flow during anaerobic digestion: Dynamic diffusion reaction models for hydrogen gas transfer in microbial flocs (1989)

Dynamic reaction diffusion models were used to analyze the consequences of aggregation for syntrophic reactions in methanogenic ecosystems. Flocs from a whey digestor were used to measure all model parameters under the in situ conditions of a particular defined biological system. Fermentation simulations without adjustable parameters could precisely predict the kinetics of H(2) gas production of digestor flocs during syntrophic methanogenesis from ethanol. The results demonstrated a kinetic compartmentalization of H(2) metabolism inside the flocs. The interspecies electron transfer reaction was mildly diffusion controlled. The H(2) gas profiles across the flocs showed high H (2) concentrations inside the flocs at any time. Simulations of the syntrophic metabolism at low substrate concentrations such as in digestors or sediments showed that it is impossible to achieve high H(2) gas turnovers at simultaneously low steady-state H(2) concentrations. This showed a mechanistic contradiction in the concept of postulated low H(2) microenvironments for the anaerobic digestion process. The results of the computer experiments support the conclusion that syntrophic H(2) production may only be a side reaction of H(2) independent interspecies electron transfer in methanogenic ecosystems.
Release of granulocyte‐macrophage colony stimulating factor by human cultured airway smooth muscle cells: suppression by dexamethasone (1997)

Smooth muscle cells represent a significant percentage of the total cells in the airway but their contribution to the inflammatory response seen in airway disease has not been studied. Hence, we have looked at the release of the cytokine granulocyte-macrophage colony stimulating factor (GM-CSF) in response to bacterial lipopolysaccharide (LPS) and the pro-inflammatory cytokines interleukin-1 beta (IL-1 beta), tumour necrosis factor alpha (TNF alpha) and interferon gamma (IFN gamma). Human airway smooth muscle (HASM) cells released GM-CSF under basal conditions (45.4 +/- 13.1 pg ml-1) that was significantly enhanced by IL-1 beta and TNF alpha with a maximal effect seen at 10 ng ml-1 (1.31 +/- 0.07 ng ml-1 and 0.72 +/- 0.16 ng ml-1, respectively). In contrast, neither LPS nor IFN gamma produced a significant increase in GM-CSF release. However, HASM cells exposed to IL-1 beta, TNF alpha and IFN gamma generated more GM-CSF than that evoked by any cytokine alone (2.2 +/- 0.15 ng ml-1). The release of GM-CSF elicited by the cytokine mixture was inhibited by cycloheximide and dexamethasone. These data suggest that HASM cells might play an active part in initiating and/or perpetuating airway inflammation in addition to controlling airway calibre.
Dispersion and Stability Studies of Resorcinarene-Encapsulated Gold Nanoparticles (2002)

Two resorcinarene surfactants with sulfur-functionalized headgroups have been evaluated for their ability to stabilize dispersions of midnanometer (16−87 nm)-sized gold particles in organic solvents. Citrate-stabilized colloidal gold nanoparticles were extracted from aqueous solutions into toluene or chloroform by tetrabenzylthiol resorcinarene 1 or tetraarylthiol resorcinarene 2. The nanoparticle dispersions were subjected to various conditions and monitored for changes in plasmon absorption intensity. The stability of the dispersions was dependent on the chemisorptive properties of the surfactant headgroup, with tetrabenzylthiol 1 being the more effective dispersant. Nanoparticles encapsulated by 1 were also highly robust, demonstrated good resistance to alkanethiol-induced flocculation, and could be redispersed after repeated precipitations in polar solvents. Surface-enhanced Raman scattering analysis and X-ray photoelectron spectroscopic studies confirmed significant differences in the chemisorptive properties of tetrathiols 1 and 2, indicating that surface passivation is an important factor in the dispersibility of colloidal gold nanoparticles in nonpolar solvents.
Cell Proliferation of Estrogen-Sensitive Cells: The Case for Negative Control* (1987)

THAT the administration of estrogens to oophorectomized vertebrates results in the proliferation of certain cell types in secondary sex organs has been acknowledged for decades (1). Whether 17β-estradiol (E2) acts directly or indirectly on the proliferation of such target cells has been widely debated without reaching a conclusive answer. Since a definitive answer to this question cannot be obtained using whole animals, researchers explored models in which rodent target tissues have been explanted in culture (2–4). However, these experimental designs were not sufficiently discriminatory to conclude whether proliferation was due directly to the estrogen interaction with the cell that was stimulated or whether intermediate steps among cell types or within cells were responsible for the effect observed (1–10). During the 60's and 70's renewed interest in characterizing the proliferative response of estrogen target tissues in whole animal models became apparent as the concept of the estrogen receptor, or estrophilins, was developed during this period (11–14). The identification of this discrete cellular marker of target cells was assumed by many to establish a direct causal relationship between estrogen and proliferation (15). Interaction with estrophilins became the obligatory step in this relationship. Cell functions thought to be regulated by estrophilins included synthesis of specific proteins (PRL, ovalbumin, conalbumin, gonadotropins, etc.) and enzymes that are important for cell proliferation (thymidine kinase, DNA polymerase, ornithine decarboxylase, etc.) (16–18). This generalization was implied within the original concepts offered by Jensen whereby estrogen target cells were defined by their estrophilin content (15). There is now general agreement that estrophilins do play an essential regulatory role in the synthesis of cell-type specific proteins, but their role in proliferation of estrogen target cells remains controversial (5). Observations which argue against a direct role of estrophilins in this context include 1) cells containing significant levels of estrophilins do not proliferate when estrogens are administered to oophorectomized animals (19); 2) cells in organs not considered typical targets (the kidney, for example) develop estrogen-sensitive tumors when an estrogen pellet is implanted in the host (20); and 3) organs not considered to be estrogen targets contain cell populations with estrophilins (19, 20). Nevertheless, many researchers consider estrophilins as direct, obligatory mediators of both cell-type specific protein synthesis and cell proliferation (21–25).
The cytokine handbook (1994)

The cytokines - an overview, I. Vilcek Molecular genetics of cytokines, G.W. Duff Interleukin-1, C.A. Dinarello Interleukin-2 and interleukin-2 receptor, S.L. Gaffen et al Interleukin-3, J.W. Schrader Interleukin-4, P. Chomarat et al Interleukin-5, C.J. Sanderson Interleukin-6, T. Hirano Interleukin-7, M.J. Maeurer et al Interleukin-8 and other CXC chemokines, A. Wuyts et al Interleukin-9, J.C. Renauld, J. Van Snick Interleukin-10, R. de Waal Malefyt, K. Moore Interleukin-11, S.E. Jacobsen Interleukin-12, W. Storkus Interleukin-13, E. de Waal Malefyt, J.E. de Vries Interleukin-15, M.K. Kennedy et al Interleukin-16,-17 and -18, M.A. Antonysamy et al Interferons, E. De Maeyer, J. Maeyer-Guinard Tumour necrosis factor, M. Zhang, K.J. Tracey Tumour necrosis factor-related ligands and receptors, C.F. Ware et al The biological complexity of transforming growth factor Beta and its receptors, Derynk, L. Choy Granulocyte-macrophage colony stimulating factor, V.F.J. Quesniaux, T.C. Jones Granulocyte colony stimulating factor, H. Murkami, S. Nagata The biochemistry of CSF-1 action, J.A. Hamilton Stem cell factor, G. Molineux, I.K. McNiece Flt3 ligand, S.D. Lyman et al The expanding universe of C1cx3 C, and C-C chemokines, K.B. Bacon et al Cytokines and anti-cytokines therapy, C. Haworth et al Clinical applications of haematopoietic growth factors, R.S. Negrin Cytokine gene therapy, I.D. Davis, M.T. Lotze Assays for cytokines, M. Wadhwa, R. Thorpe Cytokines and their receptors as potential therapeutic targets, R. Geoffrey et al The phylogeny of cytokines, C.J. Secombes.
Dynamics of Lactose Permease of Escherichia coli Determined by Site-Directed Fluorescence Labeling (1994)

Recently we described the use of site-directed pyrene labeling of engineered lactose permease containing paired Cys residues to obtain proximity relationships between helices in the C-terminal half of the molecule [Jung, K., Jung, H., Wu, J., Privé, G. G., & Kaback, H.R. (1993) Biochemistry 32, 12273]. Pyrene excimer fluorescence was detected for the double Cys mutants His322-->Cys/Glu325-->Cys, Arg302-->Cys/Glu325-->Cys, and Glu269-->Cys/His322-->Cys, indicating that helix X (His322-->Cys/Glu325-->Cys) is in an alpha-helical conformation and that helices VIII (Glu269-->Cys) and IX (Arg302-->Cys) are close to helix X (His322-->Cys and Glu325-->Cys). In this report, these interactions are used to study dynamic aspects of the permease. Excimer fluorescence between helices VIII and X or helices IX and X is markedly diminished by sodium dodecyl sulfate, while the excimer observed within helix X is unaffected, suggesting that tertiary interactions are disrupted by the denaturant with little effect on secondary structure. Furthermore, excimer fluorescence observed between helices VIII (Glu269-->Cys) and helix X (His322-->Cys) is quenched by Tl+, and the effect is markedly and specifically attenuated by ligands of the permease, suggesting that the pyrene becomes less accessible to the aqueous phase. The reactivity of single Cys residues at positions 269 or 322 was also examined by studying the rate of increase in fluorescence with N-(l-pyrenyl)maleimide. With both mutants, ligands of the permease cause a dramatic increase in reactivity which is consistent with the notion that these positions are transferred into a more hydrophobic environment.(ABSTRACT TRUNCATED AT 250 WORDS)
Noncovalent Mutant Selective Epidermal Growth Factor Receptor Inhibitors: A Lead Optimization Case Study (2015)

Because of their increased activity against activating mutants, first-generation epidermal growth factor receptor (EGFR) kinase inhibitors have had remarkable success in treating non-small-cell lung cancer (NSCLC) patients, but acquired resistance, through a secondary mutation of the gatekeeper residue, means that clinical responses only last for 8-14 months. Addressing this unmet medical need requires agents that can target both of the most common double mutants: T790M/L858R (TMLR) and T790M/del(746-750) (TMdel). Herein we describe how a noncovalent double mutant selective lead compound was optimized using a strategy focused on the structure-guided increase in potency without added lipophilicity or reduction of three-dimensional character. Following successive rounds of design and synthesis it was discovered that cis-fluoro substitution on 4-hydroxy- and 4-methoxypiperidinyl groups provided synergistic, substantial, and specific potency gain through direct interaction with the enzyme and/or effects on the proximal ligand oxygen atom. Further development of the fluorohydroxypiperidine series resulted in the identification of a pair of diastereomers that showed 50-fold enzyme and cell based selectivity for T790M mutants over wild-type EGFR (wtEGFR) in vitro and pathway knock-down in an in vivo xenograft model.