gebhart/patrepeval huggingface dataset:
Spiro piperidines. I. Synthesis of spiro[isobenzofuran-1(3H), 4'-piperidines] and spiro[isobenzofuran-1(3H), 3'-piperidines] (1975)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSpiro piperidines. I. Synthesis of spiro[isobenzofuran-1(3H), 4'-piperidines] and spiro[isobenzofuran-1(3H), 3'-piperidines]Adrian Marxer, Herman R. Rodriguez, Joseph M. McKenna, and Hsin Mei TsaiCite this: J. Org. Chem. 1975, 40, 10, 1427–1433Publication Date (Print):May 1, 1975Publication History Published online1 May 2002Published inissue 1 May 1975https://pubs.acs.org/doi/10.1021/jo00898a010https://doi.org/10.1021/jo00898a010research-articleACS PublicationsRequest reuse permissionsArticle Views850Altmetric-Citations36LEARN 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
Regulation of plant gene expression (1986)

Abstract Differential gene expression is required to establish and maintain specific developmental states in higher plants. For example, an anther has at least 11000 diverse mRNAs that are absent from the polysomes of other organ systems, and the root has at least 7000 organ-specific mRNAs. Both transcriptional and post-transcriptional processes regulate the sequence composition and prevalence distribution of each developmental-specific mRNA set. Soybean seed protein genes represent an excellent example of a highly regulated gene set. These genes are temporally and spatially regulated during embryogenesis, and are either inactive or expressed at low levels in mature plant organ systems. Gene transfer experiments indicate that soybean seed protein genes retain their developmental-specific expression programme in transformed tobacco plants. In addition, large polygenic clusters can be transferred from soybean to tobacco, and the expression pattern of each gene within the cluster is maintained in the foreign cell environment. Although the DNA sequences and cellular factors required to control seed protein gene expression are not yet known, gene transfer studies and emerging DNA binding protein technology should facilitate their identification in the near future.
Protein clefts in molecular recognition and function. (1996)

One of the primary factors determining how proteins interact with other molecules is the size of clefts in the protein's surface. In enzymes, for example, the active site is often characterized by a particularly large and deep cleft, while interactions between the molecules of a protein dimer tend to involve approximately planar surfaces. Here we present an analysis of how cleft volumes in proteins relate to their molecular interactions and functions. Three separate datasets are used, representing enzyme-ligand binding, protein-protein dimerization and antibody-antigen complexes. We find that, in single-chain enzymes, the ligand is bound in the largest cleft in over 83% of the proteins. Usually the largest cleft is considerably larger than the others, suggesting that size is a functional requirement. Thus, in many cases, the likely active sites of an enzyme can be identified using purely geometrical criteria alone. In other cases, where there is no predominantly large cleft, chemical interactions are required for pinpointing the correct location. In antibody-antigen interactions the antibody usually presents a large cleft for antigen binding. In contrast, protein-protein interactions in homodimers are characterized by approximately planar interfaces with several clefts involved. However, the largest cleft in each subunit still tends to be involved.
Augmented growth hormone (GH) secretory burst frequency and amplitude mediate enhanced GH secretion during a two-day fast in normal men (1992)

Serum GH concentrations are increased in fasted or malnourished human subjects. We investigated the dynamic mechanisms underlying this phenomenon in nine normal men by analyzing serum GH concentrations measured in blood obtained at 5-min intervals over 24 h on a control (fed) day and on the second day of a fast with a multiple-parameter deconvolution method to simultaneously resolve endogenous GH secretory and clearance rates. Two days of fasting induced a 5-fold increase in the 24-h endogenous GH production rate [78 +/- 12 vs. 371 +/- 57 micrograms/Lv (Lv, liter of distribution volume) or 0.24 +/- 0.038 vs. 1.1 +/- 0.16 mg/m2 (assuming a distribution volume of 7.9% body weight), P = 0.0001]. This enhanced GH production rate was accounted for by 2-fold increases in the number of GH secretory bursts per 24 h (14 +/- 2.3 vs. 32 +/- 2.4, P = 0.0006) and the mass of GH secreted per burst (6.3 +/- 1.2 vs. 11 +/- 1.6 micrograms/Lv, P = 0.002). The latter was a result of increased secretory-event amplitudes (maximal rates of GH release attained within a burst) with unchanged secretory burst durations. GH was secreted in complex volleys composed of multiple discrete secretory bursts. These secretory volleys were separated by shorter intervals of secretory quiescence in the fasted than fed state (respectively, 88 +/- 4.2 vs. 143 +/- 14 min, P = 0.0001). Similarly, within volleys of GH release, constituent individual secretory bursts occurred more frequently during the fast [every 33 +/- 0.64 (fasted) vs. every 44 +/- 2.0 min (fed), P = 0.0001]. The t1/2 of endogenous GH was not significantly altered by fasting [18 +/- 2.2 (fasted) vs. 20 +/- 1.5 min (fed), P = 0.47]. Serum insulin-like growth factor I concentrations were unchanged after 56 h of fasting. In conclusion, the present data suggest that starvation-induced enhancement of GH secretion is mediated by an increased frequency of GHRH release, and longer and more pronounced periods of somatostatin withdrawal.
Functional Pixel Circuits for Elastic AMOLED Displays (2005)

While fabrication of active matrix organic LED (AMOLED) displays on plastic substrates continues to face technological challenges, stable electrical operation of thin-film transistor (TFT) pixel circuits under mechanical stress induced by substrate bending remains a critical issue. This paper investigates strain-induced shifts in hydrogenated amorphous silicon TFT characteristics and the compound impact on TFT circuit behavior. Measurements show that the magnitude of the shifts is determined by the direction of current flow in the TFT with respect to the bending stress orientation as well as bias conditions. Physically based compact models are developed that relate device characteristics to material behavior for design and optimization of AMOLED pixel circuits that can maintain immunity to bending stress. In particular, current mirror-based pixel circuits are presented that compensate for the long term threshold voltage shift and instantaneous strain-induced shifts in device characteristics.
Comparison of Hyperbaric Oxygen and Dapsone Therapy for Loxosceles Envenomation (1996)

Compared with the control, neither dapsone, HBO, nor the combination of dapsone and HBO reduced necrosis from Loxosceles envenomation on days 3-21. An increase was seen in the rate of reduction in induration between all 3 treatment groups and the control group on days 7-21. However, the magnitude of this effect was clinically insignificant. In this animal model, treatment with either dapsone or HBO or a combination offers little clinical benefit in Loxosceles envenomation.
Development of a Serum Biomarker Assay That Differentiates Tumor‐Associated MUC5AC (NPC‐1C ANTIGEN) from Normal MUC5AC (2010)

A serum ELISA using a monoclonal antibody that detects a MUC5AC-related antigen (NPC-1C antigen) expressed by pancreatic and colorectal cancer was developed. The NPC-1C antibody reacts with specific epitopes expressed by tumor-associated MUC5AC that does not appear on MUC5AC from normal tissues. Based on observations of a highly specific antibody, we tested the ELISA to differentiate serum from healthy blood donors compared to serum from patients with colorectal or pancreatic cancer. Additionally, patient tumor tissue was stained to examine the expression pattern of MUC5AC-related antigen in pancreatic and colorectal cancers. The results indicate the NPC-1C antibody ELISA distinguished serum of cancer patients from normal donors with very good sensitivity and specificity. Most patient's tumor biopsy exhibited NPC-1C antibody reactivity, indicating that tumor-associated MUC5AC antigen from tumor is shed into blood, where it can be detected by the NPC-1C antibody ELISA. This serum test provides a new tool to aid in the diagnosis of these cancers and immune monitoring of cancer treatment regimens.
Theory and Tables of Optimum Symmetrical TEM-Mode Coupled-Transmission-Line Directional Couplers (1965)

New equal-ripple polynomials were determined and applied to the synthesis of symmetrical TEM-mode coupled-transmission-line directional couplers (using exact methods). Tables of designs for symmetrical couplers of three, five, seven, and nine sections having mean couplings of -3.01, -6, -8.34, -10, and -20 dB, and having several equal-ripple tolerances in the coupling band are presented. Symmetrical maximally-flat directional-coupler designs having three, five, seven, and nine sections are also presented to complete the tables.
Fc receptors are required in passive and active immunity to melanoma (1998)

Effective tumor immunity requires recognition of tumor cells coupled with the activation of host effector responses. Fc receptor (FcR) gamma-/- mice, which lack the activating Fc gamma R types I and III, did not demonstrate protective tumor immunity in models of passive and active immunization against a relevant tumor differentiation antigen, the brown locus protein gp75. In wild-type mice, passive immunization with mAb against gp75 or active immunization against gp75 prevented the development of lung metastases. This protective response was completely abolished in FcR gamma-deficient mice. Immune responses were intact in gamma-/- mice because IgG titers against gp75 develop normally in gamma-/- mice immunized with gp75. However, uncoupling of the Fc gamma R effector pathway from antibody recognition of tumor antigens resulted in a loss of protection against tumor challenge. These data demonstrate an unexpected and critical role for FcRs in mediating tumor cytotoxicity in vivo and suggest that enhancement of Fc gamma R-mediated antibody-dependent cellular cytotoxicity by inflammatory cells is a key step in the development of effective tumor immunotherapeutics.
Management of Heparin Therapy (1975)

Among 100 consecutive patients receiving heparin in therapeutic dosage, major bleeding occurred in 21, and minor bleeding in 16. Two patients died from bleeding, and two had recurrent pulmonary embolism. Major bleeding occurred in 21% when therapy was regulated with whole-blood clotting time and in 20% when heparin was given without clotting tests. In a subsequent prospective trial patients received heparin by intermittent intravenous injection with or without laboratory control according to the partial thromboplastin time or continuously by intravenous infusion. Recurrent thromboembolism occurred once in each group. Major bleeding was seven times more frequent with intermittent injection than with continuous infusion. Control with the partial thromboplastin time did not prevent major bleeding in patients receiving intermittent injections. With continuous infusion, one-fourth less heparin was required than with intermittent injections. Administration of heparin by continuous infusion appears safer than intermittent injection with or without laboratory control and is no less effective for prevention of thromboembolism.
Fractalkine and CX3CR1 Mediate a Novel Mechanism of Leukocyte Capture, Firm Adhesion, and Activation under Physiologic Flow (1998)

Leukocyte migration into sites of inflammation involves multiple molecular interactions between leukocytes and vascular endothelial cells, mediating sequential leukocyte capture, rolling, and firm adhesion. In this study, we tested the role of molecular interactions between fractalkine (FKN), a transmembrane mucin-chemokine hybrid molecule expressed on activated endothelium, and its receptor (CX3CR1) in leukocyte capture, firm adhesion, and activation under physiologic flow conditions. Immobilized FKN fusion proteins captured resting peripheral blood mononuclear cells at physiologic wall shear stresses and induced firm adhesion of resting monocytes, resting and interleukin (IL)-2-activated CD8(+) T lymphocytes and IL-2-activated NK cells. FKN also induced cell shape change in firmly adherent monocytes and IL-2-activated lymphocytes. CX3CR1-transfected K562 cells, but not control K562 cells, firmly adhered to FKN-expressing ECV-304 cells (ECV-FKN) and tumor necrosis factor alpha-activated human umbilical vein endothelial cells. This firm adhesion was not inhibited by pertussis toxin, EDTA/EGTA, or antiintegrin antibodies, indicating that the firm adhesion was integrin independent. In summary, FKN mediated the rapid capture, integrin-independent firm adhesion, and activation of circulating leukocytes under flow. Thus, FKN and CX3CR1 mediate a novel pathway for leukocyte trafficking.
Identification of the alpha IIb beta 3 integrin in murine tumor cells. (1992)

Previously, we have identified an alpha IIb beta 3-like integrin in tumor cells by using antibodies against platelet alpha IIb beta 3. However, alpha IIb beta 3 was considered to be expressed strictly in megakaryocyte lineage cells. In order to resolve this controversy, the alpha IIb beta 3-like integrin in murine B16 amelanotic melanoma (B16a) cells was characterized at DNA, RNA, and protein levels. The presence of alpha 5, alpha v, alpha IIb, beta 1, and beta 3 genes in B16a cells was confirmed by Southern analysis. mRNAs for all these integrins except alpha v were detectable by Northern blotting. The alpha IIb beta 3 protein was identified by Western blotting using subunit-specific antibodies and by immunoprecipitation using complex-specific antibody. The alpha IIb beta 3 integrin was localized intracellularly by immunocytochemistry. Finally, alpha IIb and beta 3 mRNAs were amplified by reverse transcription-polymerase chain reaction and the identity of alpha IIb was verified by sequencing. Partial DNA and deduced amino acid sequence analysis showed that B16a alpha IIb shares approximately 80% homology with the human alpha IIb and approximately 90% homology with the rat alpha IIb, whereas B16a alpha IIb shares only approximately 26% homology with the human alpha v. These experiments indicate that the alpha IIb beta 3-like protein in B16a cells is the authentic alpha IIb beta 3 and demonstrate, for the first time, that integrin alpha IIb beta 3 is not confined to megakaryocyte lineage cells.
Proposed pathogenetic cascade of inclusion-body myositis: importance of amyloid-β, misfolded proteins, predisposing genes, and aging (2003)

In conceptualizing a treatment for sporadic inclusion-body myositis, the accumulations of amyloid-beta42 and other unfolded proteins are now phenomena to be reckoned with. One would like to stop intracellular increase of the unfolded/misfolded proteins by reducing their formation and/or increasing their disposal. In addition, the identification of factors that would decrease intra-muscle fiber expressions of beta- and gamma-secretases might lead to decreased production of putatively myotoxic oligomeric amyloid-beta42. Better understanding of the mechanisms and consequences of genes that predispose to sporadic inclusion-body myositis, and of human muscle fiber aging, could also provide new avenues toward the therapy of sporadic inclusion-body myositis. How to therapeutically capitalize on the new findings is now the challenge.
MODULATORY EFEECTS OF TRIFOLIUM PRETENSE EXTRACT AND ROYAL JELLY ON THE FUNCTION OF HYPOTHALAMIC-PITUITARY-OVARIAN AXIS IN OVARIECTOMIZED RATS (2013)

Objective: This study was designed to investigate the potential estrogenic effects of phytoestrogen Trifolium pretense (red clover) and worker honey bee secretion (Royal jelly) on ovariectomized rat as a model of postmenopausal disorder. Methods: The animals were divided into 4 groups: 1- sham-operated group (Sham), 2- ovariectomized (OVX) group, 3- OVX treated orally with red clover (750mg/kg/day), 4- OVX treated orally with Royal jelly (750mg/kg/day). Uterine weight, Serum estrogen, follicular stimulating hormone (FSH), luteinizing hormone (LH)), total cholesterol, triglyceride and glucose were estimated. Neurotransmitters determination for serotonin (5-HT) and dopamine (DA) were also assayed in hypothalamus. Results: The ovariectomy caused significant reduction in uterine weight (p<0.05), as well as reduction in serum estrogen content and hypothalamic content of 5-HT and DA, whereas, it caused significant elevation in level of LH, FSH, total cholesterol, triglyceride and glucose in serum at p<0.05. The treatment with red clover and Royal jelly stimulated the uterine weight gain as a result of increase in serum estrogen level, they diminished the elevated serum FSH and LH and significantly decreased the triglycerides levels in spite of being caused no significant change in total cholesterol and glucose level. In addition, they regulate the hypothalamic neuronal function by elevation of 5HT and DA secretion as compared to OVX group. Conclusion: The results of the current study revealed that, red clover extract and Royal jelly were capable of acting at multiple targets which probably could improve function of hypothalamic-pituitary-ovarian axis in OVX rats mimicking symptoms as observed in postmenopausal females.
Oligomerization Is a General Mechanism for the Activation of Apoptosis Initiator and Inflammatory Procaspases (2003)

Proteolytic activation of initiator procaspases is a crucial step in the cellular commitment to apoptosis. Alternative models have been postulated for the activation mechanism, namely the oligomerization or induced proximity model and the allosteric regulation model. While the former holds that procaspases become activated upon proper oligomerization by an adaptor protein, the latter states that the adaptor is an allosteric regulator for procaspases. The allosteric regulation model has been applied for the activation of procaspase-9 by apoptotic protease-activating factor (Apaf-1) in an oligomeric complex known as the apoptosome. Using approaches that allow for controlled oligomerization, we show here that aggregation of multiple procaspase-9 molecules can induce their activation independent of the apoptosome. Oligomerization-induced procaspase-9 activation, both within the apoptosome and in artificial systems, requires stable homophilic association of the protease domains, raising the possibility that the function of Apaf-1 is not only to oligomerize procaspase-9 but also to maintain the interaction of the caspase-9 protease domain after processing. In addition, we provide biochemical evidence that other apoptosis initiator caspases (caspase-2 and -10) as well as a procaspase involved in inflammation (murine caspase-11) are also activated by oligomerization. Thus, oligomerization of precursor molecules appears to be a general mechanism for the activation of both apoptosis initiator and inflammatory procaspases.
A dominant positive and negative selectable gene for use in mammalian cells. (1991)

We have constructed three different fusion genes containing the herpes simplex virus thymidine kinase (HSV tk) and the bacterial neomycin phosphotransferase (neo) genes. All three fusion genes utilize the HSV tk promoter but differ at the junction of their components. We have determined if the fusion genes are bifunctional by introducing them into mammalian cells and testing for function of the individual components. One of the fusion genes, TNFUS 69, produced a bicistronic message and a fusion protein that has TK and NEO protein functions. This and other fusion genes of a similar nature could serve as dominant positive and negative selectable markers in mammalian cells.
T Cell Receptors are Structures Capable of Initiating Signaling in the Absence of Large Conformational Rearrangements (2012)

Native and non-native ligands of the T cell receptor (TCR), including antibodies, have been proposed to induce signaling in T cells via intra- or intersubunit conformational rearrangements within the extracellular regions of TCR complexes. We have investigated whether any signatures can be found for such postulated structural changes during TCR triggering induced by antibodies, using crystallographic and mutagenesis-based approaches. The crystal structure of murine CD3ε complexed with the mitogenic anti-CD3ε antibody 2C11 enabled the first direct structural comparisons of antibody-liganded and unliganded forms of CD3ε from a single species, which revealed that antibody binding does not induce any substantial rearrangements within CD3ε. Saturation mutagenesis of surface-exposed CD3ε residues, coupled with assays of antibody-induced signaling by the mutated complexes, suggests a new configuration for the complex within which CD3ε is highly exposed and reveals that no large new CD3ε interfaces are required to form during antibody-induced signaling. The TCR complex therefore appears to be a structure that is capable of initiating intracellular signaling in T cells without substantial structural rearrangements within or between the component subunits. Our findings raise the possibility that signaling by native ligands might also be initiated in the absence of large structural rearrangements in the receptor.
Electron Spin Resonance and Differential Scanning Calorimetry as Combined Tools for the Study of Liposomes in the Presence of Long Chain Nitroxides (2002)

Macroscopic and molecular techniques such as differential scanning calorimetry (DSC) and electron spin resonance (ESR), respectively, were used to characterize both structure and dynamics of liposomes built up with dioleoyltrimethylammonium propane (DOTAP) and dioleoylphosphatidylethanolamine (DOPE) lipids. These liposomes are good candidates to act as molecular carriers in cancer therapy, such as, for instance, boron neutron capture therapy (BNCT). DSC revealed that neither Tm nor ΔHm of the gel-liquid crystal phase transition depended on the presence of relatively concentrated exogenous molecules as they are the n-DSA and n-DPC spin probes used in this work. The results suggested that the structure and the internal dynamics of the liposomes did no change after small loading of the paramagnetic probes. This was proved at a molecular level by the computer analysis of the ESR spectra of the above probes, which revealed discontinuities of the motional parameters (correlation times, τ⊥ and τ∥, and order parameter S20) in the same range of temperatures of the endothermic events observed by DSC on probe-free liposomes. A dependence of τ⊥, τ∥, and S20 on the localization of the probe was found, and the activation energies for the motion were consistent with the mobility of the domains sensed by the different probes. The results reported in this work may be considered as a useful basis for the characterization of both plain and loaded liposomes when these aggregates are used as drug carriers.