gebhart/patrepeval huggingface dataset:
Chemistry of Cephalosporin Antibiotics. II. Preparation of a New Class of Antibiotics and the Relation of Structure to Activity (1962)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChemistry of Cephalosporin Antibiotics. II. Preparation of a New Class of Antibiotics and the Relation of Structure to ActivityRobert R. Chauvette, Edwin H. Flynn, Bill G. Jackson, E. R. Lavagnino, Robert B. Morin, Richard A. Mueller, Richard P. Pioch, R. W. Roeske, C. W. Ryan, John L. Spencer, and Earle. Van HeyningenCite this: J. Am. Chem. Soc. 1962, 84, 17, 3401–3402Publication Date (Print):September 1, 1962Publication History Published online1 May 2002Published inissue 1 September 1962https://pubs.acs.org/doi/10.1021/ja00876a035https://doi.org/10.1021/ja00876a035research-articleACS PublicationsRequest reuse permissionsArticle Views360Altmetric-Citations81LEARN 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 Get e-Alerts
Use of anti-HLA antibodies to mask major histocompatibility complex gene products on tumor cells can enhance susceptibility of these cells to lysis by natural killer cells. (1989)

The role of major histocompatibility gene products (i.e., HLA molecules) in rendering tumor cells resistant to natural killer (NK) cell-mediated lysis was investigated by using mouse monoclonal antibodies to bind and mask HLA or non-HLA gene products on the cell membrane of human allogeneic tumor targets. Enhanced lysis of resistant lymphoid and certain other solid tumor cell lines was observed only when monoclonals used reacted to class I and II HLA molecules but not non-HLA molecules on tumor targets. Enhanced lysis was not due to antibody dependent cellular cytotoxicity or due to an effect of antibody on NK effectors. Of importance, normal autologous and allogeneic human lymphocytes could not be lysed by NK cells despite blast transformation with mitogens or masking of HLA membrane determinants on blasts with monoclonal antibodies. Enhanced lysis, in the presence of antibody to HLA antigens, was not due to increased NK cell binding to tumor targets, but a consequence of enhanced postbinding lysis. Studies using granules obtained from NK cells indicated that masking of HLA antigens did not enhance the susceptibility of tumor targets to cytolysins. Such observations would suggest that HLA antigens on tumor targets inhibit the triggering of effector cells (and release of cytolysins) after recognition and binding of NK cells to target cells.
Polymeric Electro-optic Modulators:  From Chromophore Design to Integration with Semiconductor Very Large Scale Integration Electronics and Silica Fiber Optics (1998)

Chromophores with optimized second-order optical nonlinearity to optical loss ratios are synthesized, poled with an electrical field, and coupled into hardened polymer matrixes. Acentric order, which is necessary for electro-optic activity, is optimized by the consideration of chromophore−chromophore electrostatic interactions as well as chromophore−poling field interactions and thermal collisions which randomize chromophore orientations with respect to the applied field direction. Reactive ion etching and/or multicolor photolithography are used to fabricate buried channel waveguide structures out of the resulting polymeric electro-optic materials and to integrate polymeric waveguides with silica optical fibers. Tapered transitions are developed to minimize coupling (insertion) loss. Both vertical and horizontal integration of polymeric electro-optic modulator circuitry with semiconductor very large scale integration circuitry is demonstrated. Modulation to 113 GHz is demonstrated. Polymeric modulators are relevant to cable television, phased-array radar, ultrafast analogue-to-digital conversion, high-speed optical switching in local area networks, optical beam steering, optical backplane interconnects for parallel processors, and voltage sensing.
Immunogenicity and protection in small-animal models with controlled-release tetanus toxoid microparticles as a single-dose vaccine (1997)

Tetanus toxoid (TT) was encapsulated in microparticles prepared from polylactide-co-glycolide polymers by a solvent-evaporation technique. Combinations of small- and large-sized microparticles with controlled-release characteristics were used to immunize Sprague-Dawley rats, and the antibody responses were monitored for 1 year. For comparison, control groups of rats were immunized at 0, 1, and 2 months with TT adsorbed to alum. The antibody responses generated by the TT entrapped in microparticles were comparable to those generated by TT adsorbed to alum in control groups from 32 weeks onwards. Microparticles with a single entrapped antigen (TT) induced better antibody responses than microparticles with two antigens (TT and diphtheria toxoid) entrapped simultaneously. A combination vaccine consisting of TT adsorbed to alum and also entrapped in microparticles gave the best antibody responses. In an inhibition assay designed to determine the relative levels of binding of antisera to the antigens, the sera from the microparticle- and the alum-immunized animals showed comparable levels of binding. In addition, in a passive-challenge study with mice, TT adsorbed to alum and TT entrapped in microparticles provided equal levels of protection against a lethal challenge with tetanus toxin. An intradermal-challenge study was also performed with rabbits, which showed similar levels of protection in sera from alum- and microparticle-immunized animals at 4, 12, and 32 weeks after immunization.
A Novel Calcium-Sensing Receptor Antagonist Transiently Stimulates Parathyroid Hormone Secretion in Vivo (2005)

Circulating calcium (Ca(2+)) is a primary regulator of bone homeostasis through its action on PTH secretion. Extracellular Ca(2+) modulates PTH secretion through a cell surface G protein-coupled receptor, the calcium-sensing receptor (CaR). The expression of the CaR suggests a critical role in cellular regulation by calcium in various organs, including parathyroid gland, bone, and kidney. Despite an obvious pharmacological utility for CaR antagonists in the treatment of disease, only a limited number of such classes of compounds exist. We have identified a novel class of small molecules with specific activity at the CaR. This class of compounds is represented by compound 1. It possesses potent antagonist activity at the human CaR with IC(50) values of 64 nm and 230 nm in inhibiting intracellular Ca(2+) flux and inositol phosphate generation in vitro, respectively. When administered to male rats in vivo, compound 1 robustly increased serum PTH levels. The stimulation of PTH secretion was rapid and transient when administered either iv or orally. The pharmacokinetic profile of compound 1 after oral administration revealed that maximal plasma levels of compound were reached within 1 h and the half-life of the compound to be approximately 2 h in rats. These data describe a representative compound of a novel chemical class than previously described allosteric modulators that offer a new avenue for the development of improved treatments of osteoporosis.
Hydrolysis of Cyclic and Linear Oligomers of 6-Aminocaproic Acid by a Bacterial Cell Extract* (1966)

Journal Article Hydrolysis of Cyclic and Linear Oligomers of 6-Aminocaproic Acid by a Bacterial Cell Extract Get access TAKASHI FUKUMURA TAKASHI FUKUMURA Basic Research Laboratories, Toyo Rayon Co., Ltd.Tibiro, Kamakura Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Biochemistry, Volume 59, Issue 6, June 1966, Pages 531–536, https://doi.org/10.1093/oxfordjournals.jbchem.a128339 Published: 01 June 1966 Article history Received: 10 September 1965 Published: 01 June 1966
Mutational Analysis of Acute-Phase Response Factor/Stat3 Activation and Dimerization (1997)

Signal transducer and transcription (STAT) factors are activated by tyrosine phosphorylation in response to a variety of cytokines, growth factors, and hormones. Tyrosine phosphorylation triggers dimerization and nuclear translocation of these transcription factors. In this study, the functional role of carboxy-terminal portions of the STAT family member acute-phase response factor/Stat3 in activation, dimerization, and transactivating potential was analyzed. We demonstrate that truncation of 55 carboxy-terminal amino acids causes constitutive activation of Stat3 in COS-7 cells, as is known for the Stat3 isoform Stat3beta. By the use of deletion and point mutants, it is shown that both carboxy- and amino-terminal portions of Stat3 are involved in this phenomenon. Dimerization of Stat3 was blocked by point mutations affecting residues both in the vicinity of the tyrosine phosphorylation site (Y705) and more distant from this site, suggesting that multiple interactions are involved in dimer formation. Furthermore, by reporter gene assays we demonstrate that carboxy-terminally truncated Stat3 proteins are incapable of transactivating an interleukin-6-responsive promoter in COS-7 cells. In HepG2 hepatoma cells, however, these truncated Stat3 forms transmit signals from the interleukin-6 signal transducer gp130 equally well as does full-length Stat3. We conclude that, dependent on the cell type, different mechanisms allow Stat3 to regulate target gene transcription either with or without involvement of its putative carboxy-terminal transactivation domain.
Synthesis and evaluation of 3-substituted 17-methylmorphinan analogs as potential anticonvulsant agents (1992)

Dextromethorphan (1,(+)-3-methoxy-17-methylmorphinan) demonstrates anticonvulsant activity in a variety of in vitro and in vivo models of convulsive action. It is well known that 1 is metabolized to its phenolic derivative dextrorphan (2) and this metabolite is also a potent anticonvulsant. A series of (+)-3-substituted-17-methylmorphinans, which are structurally similar to 1 but are either not expected to be metabolized to 2 or might do so at a reduced rate, as compared to 1, were prepared. Three analogs, 5 ((+)-3-amino-17-methylmorphinan), 14 ((+)-3-ethoxy-17-methylmorphinan), and 15 ((+)-3-(2-propoxy)-17-methylmorphinan) were found to possess potent anticonvulsant activity with full efficacy (ED50 25, 5.6, and 3.9 mg/kg, sc, respectively) in the rat supramaximal electroshock (MES) test. Binding potencies of these compounds to receptor sites labeled with [3H]dextromethorphan ([3H]1), in rat brain and guinea pig brain subcellular fractions, and [3H]thienylcyclohexylpiperidine (TCP) and [3H]glycine in rat brain, were determined. Most of the analogs displaced [3H]1 from its binding sites, with compounds 14 (IC50 0.42 microM) and 15 (IC50 0.88 microM) having equivalent potencies to 1 (IC50 0.59 microM), in rat brain, and no appreciable activity at the [3H]TCP or [3H]glycine-labeled sites. Compound 5 did not bind with appreciable activity to the [3H]1 site, in rat brain, but did bind to the [3H]TCP site with lower potency than the parent 1 (IC50 7.8 and 2.0 microM, respectively). The mechanism of anticonvulsant action of these agents is not clear although it appears that interaction at the [3H]1 sites may be involved.
Tuning the Interplay between Selectivity and Permeability of ZIF-7 Mixed Matrix Membranes (2017)

Nanoparticles of zeolitic imidazolate framework-7 (nZIF-7) were blended with poly(ether imide) (PEI) to fabricate a new mixed-matrix membrane (nZIF-7/PEI). nZIF-7 was chosen in order to demonstrate the power of postsynthetic modification (PSM) by linker exchange of benzimidazolate to benzotriazolate for tuning the permeability and selectivity properties of a resulting membrane (PSM-nZIF-7/PEI). These two new membranes were subjected to constant volume, variable pressure gas permeation measurements (H<sub>2</sub>, N<sub>2</sub>, O<sub>2</sub>, CH<sub>4</sub>, CO<sub>2</sub>, C<sub>2</sub>H<sub>6</sub>, and C<sub>3</sub>H<sub>8</sub>), in which unique gas separation behavior was observed when compared to the pure PEI membrane. Specifically, the nZIF-7/PEI membrane exhibited the highest selectivities for CO<sub>2</sub>/CH<sub>4</sub>, CO<sub>2</sub>/C<sub>2</sub>H<sub>6</sub>, and CO<sub>2</sub>/C<sub>3</sub>H<sub>8</sub> gas pairs. Furthermore, PSM-nZIF-7/PEI membrane displayed the highest permeabilities, which resulted in H<sub>2</sub>/CH<sub>4</sub>, N<sub>2</sub>/CH<sub>4</sub>, and H<sub>2</sub>/CO<sub>2</sub> permselectivities that are remarkably well-positioned on the Robeson upper bound curves, thus, indicating its potential applicability for use in practical gas purifications.
CARMIL2 is a novel molecular connection between vimentin and actin essential for cell migration and invadopodia formation (2015)

Cancer cell migration requires the regulation of actin networks at protrusions associated with invadopodia and other leading edges. Carcinomas become invasive after undergoing an epithelial-mesenchymal transition characterized by the appearance of vimentin filaments. While vimentin expression correlates with cell migration, the molecular connections between vimentin- and actin-based membrane protrusions are not understood. We report here that CARMIL2 (capping protein, Arp2/3, myosin-I linker 2) provides such a molecular link. CARMIL2 localizes to vimentin, regulates actin capping protein (CP), and binds to membranes. CARMIL2 is necessary for invadopodia formation, as well as cell polarity, lamellipodial assembly, membrane ruffling, macropinocytosis, and collective cell migration. Using point mutants and chimeras with defined biochemical and cellular properties, we discovered that localization to vimentin and CP binding are both essential for the function of CARMIL2 in cells. On the basis of these results, we propose a model in which dynamic vimentin filaments target CARMIL2 to critical membrane-associated locations, where CARMIL2 regulates CP, and thus actin assembly, to create cell protrusions.
Dysregulation of cellular proliferation and apoptosis mediates human autosomal dominant polycystic kidney disease (ADPKD). (1996)

The proto-oncogene c-myc has been implicated in both cellular proliferation and apoptosis, and we have shown that overexpression of c-myc can induce polycystic kidney disease in transgenic mice. To elucidate the molecular and cellular defects underlying cystogenesis, we have investigated the potential roles of cell proliferation and apoptosis as they relate to c-myc and modulators of c-myc function in human autosomal dominant polycystic kidney disease (ADPKD). Renal c-myc expression was consistently elevated, up to 15-fold, in ADPKD. High levels of c-myc expression correlated with 10- to 100-fold increased proliferation index in cystic epithelium. Interestingly, steady-state levels of bcl-2 mRNA were also increased up to 20-fold and Bcl-2 protein was markedly elevated. In contrast, the expression of bax and p53 was virtually unchanged. However, apoptosis was consistently and significantly increased in ADPKD kidneys, unchecked by high levels of Bcl-2. Together with proliferation, apoptosis may thus represent a general mechanism for cyst growth and tissue remodeling. We conclude that both epithelial cell proliferation and apoptosis required for normal kidney homeostasis are deregulated in ADPKD, recapitulating the renal developmental program. Furthermore, abnormal expression of proto-oncogenes regulating these processes is an important mediator of cystogenesis in human ADPKD.
Platelet factor 4 promotes adhesion of hematopoietic progenitor cells and binds IL-8: novel mechanisms for modulation of hematopoiesis (2003)

Platelet factor 4 (PF4) is an abundant platelet alpha-granule C-X-C chemokine that has weak chemotactic potency but strongly inhibits hematopoiesis through an unknown mechanism. We find that PF4 binds to human CD34+ hematopoietic progenitor cells (HPCs) with a median effective concentration of 1 microg/mL but not after exposure to chondroitinase ABC. PF4 enhances adhesion of HPCs to intact stroma. Committed progenitors also adhere avidly to immobilized PF4. This adhesion is time-dependent, requires metabolic activity, causes cytoskeletal rearrangement, and induces cell-cycle inhibition. Using extracellular acidification rate to indicate transmembrane signaling, we find that interleukin-8 (IL-8), but not PF4, activates CD34+ progenitors, and PF4 blocks IL-8-mediated activation. Surface plasmon resonance analysis shows that PF4 binds IL-8 with high (dissociation constant [Kd] = 42 nM) affinity. Nuclear magnetic resonance analysis of IL-8 and PF4 in solution confirms this interaction. We conclude that PF4 has the capacity to influence hematopoiesis through mechanisms not mediated by a classical high-affinity, 7-transmembrane domain chemokine receptor. Instead, PF4 may modulate the hematopoietic milieu both directly, by promoting progenitor adhesion and quiescence through interaction with an HPC chondroitin sulfate-containing moiety, and indirectly, by binding to or interfering with signaling caused by other, hematopoietically active chemokines, such as IL-8.
Hybridomas for production of monoclonal antibodies to human erythropoietin (1984)

Human urinary erythropoietin has been highly purified by a combination of conventional purification methods and immunoadsorbent columns packed with hybridoma-produced antibodies against contaminants that seemed difficult to separate from erythropoietin by the usual means. By using the partially purified erythropoietin as an antigen, three hybridoma clones have been obtained that secrete monoclonal antibodies against erythropoietin. One of the clones has been quite stable, with a rapid growth rate and high production of antibody. Western blotting technique with monoclonal antibodies revealed occurrence of two species of erythropoietin. The monoclonal antibody will be useful as a probe for the purification of erythropoietin and for further studies of the hormone and its mechanism of action.
Acoustic barcodes (2012)

We present acoustic barcodes, structured patterns of physical notches that, when swiped with e.g., a fingernail, produce a complex sound that can be resolved to a binary ID. A single, inexpensive contact microphone attached to a surface or object is used to capture the waveform. We present our method for decoding sounds into IDs, which handles variations in swipe velocity and other factors. Acoustic barcodes could be used for information retrieval or to triggering interactive functions. They are passive, durable and inexpensive to produce. Further, they can be applied to a wide range of materials and objects, including plastic, wood, glass and stone. We conclude with several example applications that highlight the utility of our approach, and a user study that explores its feasibility.
Patterns of Response of Some Physiological Indices of Stress in Pigs Negotiating Loading Ramps (1993)

Many reports have examined the effect of subjecting animals to stress and a variety of physiological indices have been used to monitor their responses. The indices are often only measured at one point in time and compared to resting levels. Problems could arise in interpretation of the results especially where there is little or no information on the time course of response. This work examined the pattern or response of various indices to the stress of negotiating a loading ramp. Four pigs of approximately 60 kg live weight were surgically prepared and indwelling catheters placed in both jugular veins. The animals were allowed to recover for three days and to become accustomed to the blood sampling procedure before the experiment. The pigs were driven individually up a 2.44m long ramp which was set at an angle of 34° lo the horizontal, the maximum allowed under UK legislation for internal vehicle ramps (Transport of Animals (Road and Rail) Order, 1975). Nine blood samples were removed at intervals from each pig. The whole process was repealed on each individual pig for three days.
Fluorescent 7-Deazapurine Derivatives from 5-Iodocytosine via a Tandem Cross-Coupling-Annulation Reaction with Terminal Alkynes (2004)

Fluorescent bicyclic analogs of cytosine have been ­synthesized directly from derivatives of 5-iodocytosine by a one-pot sequential Sonogashira cross-coupling and annulation with terminal alkynes. The spectral properties of these compounds depend on the identity of the alkyne. 7-Deazapurines synthesized from ­substituted phenylacetylenes possess greater fluorescence than those derived from alkyl substituted alkynes.
The Pathogenesis of Chronic Obstructive Pulmonary Disease (2005)

In 1826, Laennec said of emphysema that “it consists simply in the dilatation of the air cells” (1). Osler’s 1892 Textbook of Medicine stated that hypertrophic emphysema, also known as substantive or idiopathic emphysema, “is a well marked clinical affection, characterized by enlargement of the lungs due to distention of the air cells and atrophy of their walls, and clinically by imperfect aeration of the blood and more or less marked dyspnea” (2). The pathologic description of chronic obstructive pulmonary disease (COPD) in this text was beautiful: “Grossly, the lungs are large, they have lost their elasticity, and to touch they have a peculiar downy, feathery feel, and pit readily against pressure.... In the larger tubes (bronchi) the mucous membrane may be rough and thickened from chronic bronchitis. Microscopically, there is seen atrophy of the alveolar walls, by which is produced the coalescence of neighboring air-cells.” Insights regarding etiology and pathogenesis were not as prescient. The prevailing hypothesis regarding pathogenesis was that air cells received heightened pressure during forced expiratory efforts. Support for this theory came from the contention that there was a high frequency of the condition in “players of wind instruments, in glass blowers, and in occupations necessitating heavy lifting or straining.” While our current understanding of COPD pathogenesis has progressed, this idea is not as dated as it seems. A recent accurate computer model of emphysema was generated by combining initial proteolytic damage of extracellular matrix in a centriacinar heterogeneous manner with subsequent respiratory forces that propagate this injury (Figure 1) (3).