bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nitric Oxide as a Modulator of Gastric Mucin Synthesis: Role of ERK and p38 Mitogen‐Activated Protein Kinase Activation
Authors: Slomiany Bronislaw L. , Slomiany Amalia 
Published: September 2003

AbstractNitric oxide (NO) is an important biological messenger in the regulation of tissue homeostasis and pathophysiological processes. Here, we investigated the effect of NO on gastric mucus glycoprotein (mucin) synthesis, apoptotic processes, and the involvement of extracellular signal‐regulated kinase (ERK) and p38 mitogen‐activated protein kinase (MAPK). Exposure of gastric mucosal cells to NO donor led to a dose‐dependent decrease (up to 48%) in mucin synthesis, accompanied by a marked increase in caspase‐3 activity and apoptosis. Inhibition of ERK with PD98059 accelerated (up to 23.8%) the NO‐induced decrease in mucin synthesis, and cause further enhancement in caspase‐3 activity and apoptosis. Blockade of p38 kinase with SB203580 produced reversal in the NO‐induced reduction in mucin synthesis, and substantially countered the induced increase in caspase‐3 activity and apoptosis. Moreover, caspase‐3 inhibitor not only blocked the NO‐induced increase in caspase‐3 activity but also produced an increase in mucin synthesis. Thus, the detrimental influence of NO on mucin synthesis is closely linked to caspase‐3 activation and apoptosis, and involves ERK and p38 kinase participation. Activation of p38 kinase leads to the upregulation of proapoptotic signal, while ERK activation stimulates the anti‐apoptotic pathway.
Inhibition of PKCβ Improves Glucocorticoid‐Induced Insulin Resistance in Rat Adipocytes
Authors: Kawai Yasunori , Ishizuka Tatsuo , Kajita Kazuo , Miura Atsushi , Ishizawa Masayoshi , Natsume Yoshiyuki , Uno Yoshihiro , Morita Hiroyuki , Yasuda Keigo 
Published: September 2003

AbstractPretreatment with glucocorticoids for 60 min depressed insulin‐stimulated uptake of 2‐[ 3 H] deoxyglucose (2‐DOG), an effect that neither cycloheximide, an inhibitor of protein synthesis, nor RU38486, a glucocorticoid receptor antagonist, could restore. Preincubation with conventional PKC inhibitors restored dexamethasone‐induced insulin resistance. We also examined the dexamethasone‐mediated inhibitory effect on insulin‐induced 2‐DOG uptake in adipocytes overexpressed with wild‐type and dominant negative forms of PKC β. The dexamethasone‐mediated inhibitory effect on insulin‐induced 2‐DOG uptake was abrogated in adipocytes overexpressed with dominant‐negative PKC β. These results indicate that PKC βmay play an important role in glucocorticoid‐induced insulin resistance.
Integration of Amplified Differential Gene Expression (ADGE) and DNA Microarray
Authors: Chen Zhijian J. , Gaté Laurent , Davis Warren , Ile Kristina E. , Tew Kenneth D. 
Published: September 2003

AbstractAmplified Differential Gene Expression (ADGE) provides a new concept that the ratios of differentially expressed genes are magnified before detection in order to improve both sensitivity and accuracy. This technology is now implemented with integration of DNA reassociation and PCR. The ADGE technique can be used either as a stand‐alone method or in series with DNA microarray. ADGE is used in sample preprocessing and DNA microarray is used as a displaying system in the series combination. These two techniques are mutually synergistic: the quadratic magnification of ratios of differential gene expression achieved by ADGE improves the detection sensitivity and accuracy; the PCR amplification of templates enhances the signal intensity and reduces the requirement for large amounts of starting material; the high throughput for DNA microarray is maintained.
Zinc Fingers‐‐Folds for Many Occasions
Authors: Matthews Jacqueline M. , Sunde Margaret 
Published: September 2003

AbstractZinc finger domains (ZnFs) are common, relatively small protein motifs that fold around one or more zinc ions. In addition to their role as a DNA‐binding module, ZnFs have recently been shown to mediate protein:protein and protein:lipid interactions. This small zinc‐ligating domain, often found in clusters containing fingers with different binding specificities, can facilitate multiple, often independent intermolecular interactions between nucleic acids and proteins. Classical ZnFs, typified by TFIIIA, ligate zinc via pairs of cysteine and histidine residues but there are at least 14 different classes of Zn fingers, which differ in the nature and arrangement of their zinc‐binding residues. Some GATA‐type ZnFs can bind to both DNA and a variety of other proteins. Thus proteins with multiple GATA‐type fingers can play a complex role in regulating transcription through the interplay of these different binding selectivities and affinities. Other ZnFs have more specific functions, such as DNA‐binding ZnFs in the nuclear hormone receptor proteins and small‐molecule‐binding ZnFs in protein kinase C. Some classes of ZnFs appear to act exclusively in protein‐only interactions. These include the RING family of ZnFs that are involved in ubiquitination processes and in the assembly of large protein complexes, LIM, TAZ, and PHD domains. We review the similarities and differences in structure and functions of different ZnF classes and highlight the versatility of this fold.
The Role of Troponins in Muscle Contraction
Authors: Gomes Aldrin V. , Potter James D. , Szczesna‐Cordary Danuta 
Published: September 2003

AbstractTroponin (Tn) is the sarcomeric Ca 2+ regulator for striated (skeletal and cardiac) muscle contraction. On binding Ca 2+ Tn transmits information via structural changes throughout the actin‐tropomyosin filaments, activating myosin ATPase activity and muscle contraction. Although the Tn‐mediated regulation of striated muscle contraction is now well understood, the role of different Tn isoforms in these processes is the subject of intensive investigations. This review addresses the physiological significance of the multiple Tn isoforms in skeletal and cardiac muscles as well as their role in the regulation of contraction.
Mood‐Enhancing Antidepressant St. John's Wort Inhibits the Activation of Human Immunodeficiency Virus Gene Expression by Ultraviolet Light
Authors: Taher Mohiuddin M. , Lammering Guido M. , Hershey Chad M. , Valerie Kristoffer C. 
Published: September 2003

AbstractUltraviolet (UV) radiation is a potent activator of the human immunodeficiency virus (HIV) gene expression in a HeLa cell clone with stably integrated copies of the HIVcat reporter construct. Recently, we have shown that activation of p38 MAP kinase and NF‐ κB is necessary but not sufficient for triggering efficient HIV gene expression in response to UV. Here we demonstrate that St. John's wort is a potent inhibitor of the UV‐induced activation of HIV gene expression in HeLa cells. Stably transfected HIVcat/HeLa cells were preincubated with different amounts (25‐100 μl) of St. John's wort or gingko biloba extracts for 30 min, then irradiated with UV (30 J/m 2 ). In contrast to ginkgo biloba, St. John's wort inhibited the UV‐induced HIV gene expression in a dose‐dependent manner. Furthermore, preincubation with St. John's wort (10, 20, and 30 μl) for 30 min before UV (30 J/m 2 ) irradiation, PMA‐ and UV‐induced NF‐ κB activation was completely blocked, whereas ginkgo biloba did not affect the PMA‐ and UV‐induced NF‐ κB activation in HeLa cells. UV activation of p38 MAP kinase was not inhibited by St. John's wort or by ginkgo biloba. However, we found that p38 MAP kinase and JNK1 and ‐2 were activated by St. John's wort, but p44/42 MAP kinase was not activated by St. John's wort in HeLa cells. Hypericin an active ingredient in St. John's wort also inhibited the UV activation of HIV gene expression in HeLa cells. These results firmly confirm that St. John's wort is a potent inhibitor of the UV‐induced activation of HIV gene expression in HeLa cells.
Harmonic Maps and Morphisms from Multilinear Norm-Preserving Mappings
Authors: Baird Paul , Ou Ye-Lin 
Published: September 2003

We extend the notion of orthogonal multiplication to multilinear norm-preserving mapping, using them to construct new eigenmaps into spheres. We characterize those which are harmonic morphisms. By the method of reduction we construct interesting families of harmonic morphisms into S2 from the product manifolds H2 × S3 and S3 × S3 of hyperbolic spaces and spheres. The corresponding reduction equation depends on two independent variables. We are able to solve the first-order horizontal conformality problem explicitly in terms of elliptic functions and then render the map harmonic by a conformal deformation of the metric.
THE UNIVERSE OF FLUCTUATIONS
Authors: SIDHARTH B. G. 
Published: September 2003

We discuss the recent model of a Quantum Mechanical Black Hole (QMBH) which describes the most fundamental known particles, the leptons and approximately the quarks in terms of the Kerr–Newman Black Hole with a naked singularity shielded by Zitterbewegung effects. This goes beyond the Zitterbewegung and self interaction models of Barut and Bracken, Hestenes, Chacko and others and provides a unified picture which amongst other things gives a rationale for and an insight into: (1) The apparently inexplicable reason why complex space–time transformations lead to the Kerr–Newman metric in General Relativity. (2) The value of the fine structure constant. (3) The ratio between electromagnetic and gravitational interaction strengths. (4) The anomalous gyromagnetic ratio for the electron. (5) Why the neutrino is left-handed. (6) Why the charge is discrete. In the spirit of Effective Field Theories, this model provides an alternative formalism for Quantum Theory and also for its combination with General Relativity. Finally a mechanism for the formation of these QMBH or particles is explored within the framework of Stochastic Electrodynamics, QED and Quantum Statistical Mechanics. The cosmological implications are then examined. It turns out that a surprisingly large number of facts, including some which were hitherto inexplicable. follow as a consequence of the model. These include a theoretical deduction of the Mass, Radius and Age of the Universe, also the values of Hubble's constant and the Cosmological constant.
STATUS AND PERSPECTIVES OF DOUBLE BETA DECAY — WINDOW TO NEW PHYSICS BEYOND THE STANDARD MODEL OF PARTICLE PHYSICS
Authors: KLAPDOR-KLEINGROTHAUS H. V. 
Published: September 2003

Nuclear double beta decay provides an extraordinarily broad potential to search for beyond Standard Model physics, probing already now the TeV scale, on which new physics should manifest itself. These possibilities are reviewed here. First, the results of present generation experiments are presented. The most sensitive one of them — the Heidelberg–Moscow experiment in the Gran Sasso — probes the electron mass now in the sub eV region and will reach a limit of ~ 0.1 eV in a few years. Basing to a large extent on the theoretical work of the Heidelberg Double Beta Group in the last two years, results are obtained also for SUSY models (R-parity breaking, sneutrino mass), leptoquarks (leptoquark–Higgs coupling), compositeness, right-handed W boson mass and others. These results are comfortably competitive to corresponding results from high-energy accelerators like TEVATRON, HERA, etc. Second, future perspectives of ββ research are discussed. A new Heidelberg experimental proposal (GENIUS) is presented which would allow one to increase the sensitivity for Majorana neutrino masses from the present level of at best 0.1 eV down to 0.01 or even 0.001 eV. Its physical potential would be a breakthrough into the multi-TeV range for many beyond standard models. Its sensitivity for neutrino oscillation parameters would be higher than that for all present terrestrial neutrino oscillation experiments and of those planned for the future. It could probe directly the atmospheric neutrino problem and even the large angle solution of the solar neutrino problem. It would further, already in a first step, using only 100 kg of natural Ge detectors, cover almost the full MSSM parameter space for prediction of neutralinos as cold dark matter, making the experiment competitive to LHC in the search for supersymmetry.
SOME ASPECTS OF GEOMETRICAL CONFINEMENT
Authors: NOVELLO M. , DE LORENCI V. A. , ELBAZ E. 
Published: September 2003

In this paper we present a toy model for the dynamics of a gauge field theory in such a way that spin-one particles can be confined in a compact domain. We show that the property of confinement can be associated to the formation of a null surface identified to a horizon. This is due to the presence of an effective geometry generated by the self-interaction of the gauge field that guides the wave propagation of the field. This phenomenon has a striking analogy to the gravitational black hole in Einstein's general theory of relativity, separating two domains of space–time that can be trespassed only into one direction.
METHOD OF SOLVING CONFORMAL MODELS IN D-DIMENSIONAL SPACE II A FAMILY OF EXACTLY SOLVABLE MODELS IN D>2
Authors: FRADKIN E. S. , YA. PALCHIK M. 
Published: September 2003

We study a family of exactly solvable models of conformally invariant quantum field theory in D-dimensional space. We demonstrate the existence of D-dimensional analogs of primary and secondary fields. Under the action of the energy–momentum tensor and conserved currents, the primary field creates an infinite set of (tensor) secondary fields of different generations. The commutators of secondary fields with zero components of the current and energy–momentum tensor include anomalous operator terms. We show that the Hilbert space of conformal theory has a special sector whose structure is solely defined by the Ward identities independently of the choice of dynamical model. The states of this sector are constructed from secondary fields. Definite self-consistent conditions on the states of the latter sector fix the choice of the field model uniquely. The above self-consistent conditions are formulated as follows. Special superpositions Qs, s= 1, 2, …, of secondary fields are constructed. Each superposition is determined by the requirement that the form of its commutators with energy–momentum tensor of a primary fiel d. Each equation Qs(x)=0 is consistent, and defines an exactly solvable model for D ≥ 3. The structure of these models is analogous to that of well-known two-dimensional conformal models. The states Qs(x)|0> are analogous to the null vectors of two-dimensional theory. In each of these models one can obtain a closed set of differential equations for all the higher Green functions, as well as algebraic equations relating the scale dimension of the fundamental field to the D-dimensional analog of a central charge. As an example, we present a detailed discussion on a pair of exactly solvable models in even-dimensional space D≥4.
METHOD OF SOLVING CONFORMAL MODELS IN D-DIMENSIONAL SPACE III SECONDARY FIELDS IN D>2 AND THE SOLUTION OF TWO-DIMENSIONAL MODELS
Authors: FRADKIN E. S. , YA. PALCHIK M. 
Published: September 2003

We proceed with the study (started in Refs. 1 and 2) of the Hilbert space of conformal field theory in D di mensions. We discuss an infinite family of secondary fields [Formula: see text] generated by the action of the components of energy–momentum tensor Tμν on the fundamental (primary) field. It is shown that the states of these fields form a specific sector of the Hilbert space H which is determined by the Ward identities and [Formula: see text]-dimensional conformal symmetry. We demonstrate that for D = 2 the subspace H coincides with the space of representation of the Virasoro algebra. Each exactly solvable model in the case of D ≥ 2 is defined by the requirement of vanishing of a certain state Qs(x)|0> ⊂ H analogous to the null vector of two-dimensional theory. The Green functions of the fields [Formula: see text] are calculated in terms of the Green functions of the fundamental field. It is shown that all the Green functions of the type [Formula: see text] satisfy the anomalous Ward identities. The anomalous contributions are given by the fields [Formula: see text], where s′≤s-1. The fields Qs are constructed as superpositions of secondary fields with the anomalous contribution equal to zero, An approach developed is based on a finite-dimensional conformal symmetry for any D ≥ 2. Nevertheless the resulting models have the structure analogous to that of two-dimensional conformal theories. This analogy is discussed in detail. It is shown that for D = 2 the family of models coincides with the well-known family of conformal models based on infinite-dimensional conformal symmetry. The analysis of this phenomenon indicates the existence of the D-dimensional analog of the Virasoro algebra.
A BURGE TREE OF VIRASORO-TYPE POLYNOMIAL IDENTITIES
Authors: FODA OMAR , LEE KEITH S. M. , WELSH TREVOR A. 
Published: September 2003

Using a summation formula due to Burge, and a combinatorial identity between partition pairs, we obtain an infinite tree of q-polynomial identities for the Virasoro characters [Formula: see text], dependent on two finite size parameters M and N, in the cases where: (1) p and p′ are coprime integers that satisfy 0 < p < p′. (2) If the pair (p′:p) has a continued fraction (c1, c2, …, ct-1, ct+2), where t≥1, then the pair (s:r) has a continued fraction (c1, c2, …, cu-1, d), where 1 ≤ u ≤ t, and 1 ≤ d ≤ cu. The limit M → ∞, for fixed N, and the limit N → ∞, for fixed M, lead to two independent boson-fermion-type q-polynomial identities: in one case, the bosonic side has a conventional dependence on the parameters that characterize the corresponding character. In the other, that dependence is not conventional. In each case, the fermionic side can also be cast in either of two different forms. Taking the remaining finite size parameter to infinity in either of the above identities, so that M → ∞ and N → ∞, leads to the same q-series identity for the corresponding character.
Immunomodulatory drug costimulates T cells via the B7-CD28 pathway
Authors: LeBlanc Richard , Hideshima Teru , Catley Laurence P. , Shringarpure Reshma , Burger Renate , Mitsiades Nicholas , Mitsiades Constantine , Cheema Puneet , Chauhan Dharminder , Richardson Paul G. , Anderson Kenneth C. , Munshi Nikhil C. 
Published: September 2003

AbstractAlthough thalidomide (Thal) does not directly induce T-cell activation, it increases proliferation of T cells following CD3 activation. In this study, we examined the immunomodulatory effects of a more potent analog of Thal, immunomodulatory drug (IMiD), on T cells. Although IMiD3 does not directly stimulate proliferation of normal donor CD3+ T cells, it significantly costimulates proliferation of CD3+ T cells induced by CD3 ligation (stimulation index [SI], 2.4), immature dendritic cells (DCs; SI, 2.1), and mature DCs (SI, 2.6). T-cell proliferation triggered by DCs was abrogated by cytotoxic T lymphocyte antigen 4–immunoglobulin (CTLA-4–Ig), and IMiD3 partially overcomes this inhibitory effect. IMiD3 also overcomes the inhibitory effects of CTLA-4–Ig on Epstein-Barr virus (EBV) and influenza (Flu)–specific CD4 and CD8 T-cell responses, as measured by cytokine capture and enzyme-linked immunosorbent spot (ELISPOT) assay. IMiD3 did not induce up-regulation of CD28 expression on T cells, or of CD80-CD86 expression on dendritic cells. Importantly, IMiD3 triggers tyrosine phosphorylation of CD28 on T cells, followed by activation of nuclear factor κB (NF-κB), a known downstream target of CD28 signaling. These results therefore define the costimulatory mechanism whereby IMiD3 induces T-cell activation and provide the cellular and molecular basis for use of IMiD3 as an adjuvant in immunotherapeutic treatment strategies for multiple myeloma.
Therapeutic activation of Vα24+Vβ11+ NKT cells in human subjects results in highly coordinated secondary activation of acquired and innate immunity
Authors: Nieda Mie , Okai Miki , Tazbirkova Andrea , Lin Henry , Yamaura Ayako , Ide Kazuki , Abraham Rick , Juji Takeo , Macfarlane David J. , Nicol Andrew J. 
Published: September 2003

AbstractHuman Vα24+Vβ11+ natural killer T (NKT) cells are a distinct CD1d-restricted lymphoid subset specifically and potently activated by α-galactosylceramide (α-GalCer) (KRN7000) presented by CD1d on antigen-presenting cells. Preclinical models show that activation of Vα24+Vβ11+ NKT cells induces effective antitumor immune responses and potentially important secondary immune effects, including activation of conventional T cells and NK cells. We describe the first clinical trial of cancer immune therapy with α-GalCer–pulsed CD1d-expressing dendritic cells. The results show that this therapy has substantial, rapid, and highly reproducible specific effects on Vα24+Vβ11+ NKT cells and provide the first human in vivo evidence that Vα24+Vβ11+ NKT cell stimulation leads to activation of both innate and acquired immunity, resulting in modulation of NK, T-, and B-cell numbers and increased serum interferon-γ. We present the first clinical evidence that Vα24+Vβ11+ NKT cell memory produces faster, more vigorous secondary immune responses by innate and acquired immunity upon restimulation.
Congenital thrombotic thrombocytopenic purpura in association with a mutation in the second CUB domain of ADAMTS13
Authors: Pimanda John E. , Maekawa Akiko , Wind Troels , Paxton Julian , Chesterman Colin N. , Hogg Philip J. 
Published: September 2003

AbstractSevere deficiency of the von Willebrand Factor (VWF)–cleaving proteinase, ADAMTS13, is associated with the development of thrombotic thrombocytopenic purpura (TTP). Several mutations spread across the ADAMTS13 gene have been identified in association with a deficiency of VWF-cleaving proteinase activity in patients with congenital TTP. The spread of these dysfunctional mutations and the domain structure of ADAMTS13 are suggestive of a complex interaction between the enzyme and its substrate. We have studied a patient with congenital TTP who is a compound heterozygote for the Thr196Ile mutation in the metalloproteinase domain and a frameshift mutation (4143-4144insA) in the second CUB domain that results in loss of the last 49 amino acids of the protein. The VWF-cleaving proteinase activity of the truncated enzyme was comparable to that of the wild-type enzyme but its secretion from transfected COS-7 cells was about 14% of the wild type.
Intravenously applied IgG stimulates complement attenuation in a complement-dependent autoimmune disease at the amplifying C3 convertase level
Authors: Lutz Hans U. , Stammler Pia , Bianchi Valentina , Trüeb Ralph M. , Hunziker Thomas , Burger Reinhard , Jelezarova Emiliana , Späth Peter J. 
Published: September 2003

AbstractIntravenously applied normal human immunoglobulin G (IgG) has anti-inflammatory effects in the treatment of autoimmune diseases. Systemic inflammation can originate from an overreacting amplification loop of the complement system. In blood, C3b2-containing complexes maintain complement amplification much better than the extremely short-lived C3b. Therefore, in patients with the complement-dependent autoimmune disease, dermatomyositis, we studied whether intravenously applied normal human IgG (IVIG) stimulated in vivo inactivation of these complexes. In the course of IVIG treatment, clinically effective in 6 of 8 patients, the concentration of C3b2-containing complexes dropped to 37% ± 14% (n = 6) of the pretreatment level when having infused 0.5 g IgG/kg body weight, increased marginally and in parallel to factor Bb thereafter until full-dose IgG was infused. By day 14 following infusion of 2 g IgG/kg body weight the concentration of C3b2-containing complexes was 66% ± 19%. The plasma concentration of C3 remained constant in myopathic or increased by 15% to 20% in amyopathic patients. In contrast to this, IVIG infusion was associated with consumption of up to 40% of plasma C4 at day 1 to 2 after completion of IVIG infusion. Thus, IVIG had an immediate and long-lasting attenuating effect on complement amplification in vivo, despite the fact that it induced classical complement pathway activation.