bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of an alkylammonium-montmorillonite-phenanthrene intercalation complex by carbon-13 nuclear magnetic resonance spectroscopy
Authors: Theng B. K. G. , Newman R. H. , Whitton J. S.
Published: July 2002

Low molecular weight polycyclic aromatic hydrocarbons can intercalate from the solid phase into montmorillonite (Mt) saturated with quaternary alkylammonium ions. However, the interaction and relationship between guest and host organic molecules in the interlayer space of the clay are not well understood. We have intercalated phenanthrene into tetradecyltrimethylammonium (TDTMA)-montmorillonite by a solid-solid reaction. The basal spacing of the original TDTMA-Mt complex is close to 1.8 nm, indicating the presence in the interlayer space of a double layer of TDTMA ions with the alkyl (polymethylene) chains lying parallel to the silicate layers, and the carbon zig-zags adopting an all-trans conformation. After intercalation of phenanthrene the basal spacing increases to about 3.4 nm, indicating a change in orientation of the alkyl chains with respect to the silicate layers. 13C-NMR spectroscopy shows that adding phenanthrene to TDTMA-Mt leads to a displacement by -3 ppm of the -(CH2)n- signal for TDTMA. This signal and that for interlayer phenantbrene are also broadened relative to the respective pure compounds. These observations, together with measurements of nuclear spin relaxation time constants, strongly suggest that in the complex with phenanthrene the polymethylene chains of TDTMA extend away from the silicate layers, and no longer assume a rigid all-trans carbon zig-zag conformation. Rather, the TDTMA chains become relatively disordered and intimately mixed with phenanthrene.
Textural properties of synthetic clay-ferrihydrite associations
Authors: Celis R. , Cornejo J. , Hermosin M. C.
Published: July 2002

Kaolinite-ferrihydrite and montmorillonite-ferrihydrite associations were prepared following a procedure based on the Russell method for the synthesis of ferrihydrite and the texture of the clay-ferrihydrite complexes was studied using different techniques. The textural properties of kaolinite were little affected by the Fe association, showing only a slight increase in the specific surface area measured by nitrogen adsorption and a decrease in the largest pores (>10 µm), as measured by mercury porosimetry. In contrast, the nitrogen specific surface area of the montmorillonite complexes was much higher than that of the clay without Fe and the pore structure depended on the amounts of Fe in the complexes. Application of the fractal approach to nitrogen adsorption data indicated that the surface roughness (microporosity) was greater for the complexes prepared from diluted Fe(III) solutions, in agreement with the information obtained from classical interpretation of the adsorption isotherms (shape of the isotherms and t-plots).
Barian-titanian micas from Ilha da Trindade, South Atlantic
Authors: Greenwood J. C.
Published: July 2002

Extremely high abundances of TiO2 (up to 12.57 wt.%) and BaO (up to 7.11 wt.%) are reported from dark reddish-brown phlogopite-biotite rims around paler phlogopite cores in a lamprophyric dyke from Ilha da Trindade, South Atlantic. Both TiO2 and BaO contents increase towards the rims of the micas and in groundmass crystals. This is accompanied by corresponding increases in FeO*, MnO and Mg number; whereas SiO2, Al2O3, Cr2O3, MgO and K2O abundances all decrease. The substitution of Ba into the biotite structure can be explained by the scheme Ba + Al = K + Si. Ti-substitution schemes however are much more complex, as no general equation can account for all the Ti incorporated into the structure and therefore several schemes are proposed.
Ligand binding to integrin αvβ3requires tyrosine 178 in the αv subunit
Authors: Honda Shigenori , Tomiyama Yoshiaki , Pampori Nisar , Kashiwagi Hirokazu , Kiyoi Teruo , Kosugi Satoru , Tadokoro Seiji , Kurata Yoshiyuki , Shattil Sanford J. , Matsuzawa Yuji
Published: July 2002

Integrin αvβ3 has been implicated in angiogenesis and other biological processes. However, the ligand-binding sites in αv, a non–I-domain α subunit, remain to be identified. Recently in αIIb, the other partner of the β3 subunit, several discontinuous residues important for ligand binding were identified in the predicted loops between repeats 2 and 3 (W3 4-1 loop) and within repeat 3 (W3 2-3 loop). Based on these findings, alanine-scanning mutagenesis in 293 cells was used to investigate the role of these loops (cysteine [C]142-C155 and glycine [G]172-G181) of αv in ligand binding. Wild-type αvβ3 was able to bind soluble fibrinogen following integrin activation either by 0.5 mM manganese dichloride (MnCl2) or a mutation of β3 threonine (T)562 to asparagine. However, mutation of tyrosine (Y)178 to alanine in the predicted G172-G181 loop of αv abolished fibrinogen binding, and alanine (A) substitutions at adjacent residues phenylalanine (F)177 and tryptophan (W)179 had a similar effect. Cells expressing Y178Aαvalso failed to bind to immobilized fibrinogen. Moreover, the Y178A mutation abolished the binding of WOW-1 Fab, a monovalent ligand-mimetic anti-αvβ3 antibody, and the expression of β3 ligand–induced binding sites (LIBS) induced by arginine-glycine-aspartic acid-tryptophan (RGDW). In sharp contrast to the data obtained with αIIb, none of the mutations in the predicted W3 4-1 loop in αv impaired ligand binding. These results implicate αv Y178 in ligand binding to αvβ3, and they suggest that there are key structural differences in the adhesive ligand-binding sites of αvβ3 and αIIbβ3.
The interaction between Cdc42 and WASP is required for SDF-1–induced T-lymphocyte chemotaxis
Authors: Haddad Elie , Zugaza José L. , Louache Fawzia , Debili Najet , Crouin Catherine , Schwarz Klaus , Fischer Alain , Vainchenker William , Bertoglio Jacques
Published: July 2002

In studies aimed at further characterizing the cellular immunodeficiency of the Wiskott-Aldrich syndrome (WAS), we found that T lymphocytes from WAS patients display abnormal chemotaxis in response to the T-cell chemoattractant stromal cell–derived factor (SDF)-1. The Wiskott- Aldrich syndrome protein (WASP), together with the Rho family GTPase Cdc42, control stimulus-induced actin cytoskeleton rearrangements that are involved in cell motility. Because WASP is an effector of Cdc42, we further studied how Cdc42 and WASP are involved in SDF-1–induced chemotaxis of T lymphocytes. We provide here direct evidence that SDF-1 activates Cdc42. We then specifically investigated the role of the interaction between Cdc42 and WASP in SDF-1–responsive cells. This was achieved by abrogating this interaction with a recombinant polypeptide (TAT-CRIB), comprising the Cdc42/Rac interactive binding (CRIB) domain of WASP and a human immunodeficiency virus–TAT peptide that renders the fusion protein cell-permeant. This TAT-CRIB protein was shown to bind specifically to Cdc42-GTP and to inhibit the chemotactic response of a T-cell line to SDF-1. Altogether, these data demonstrate that Cdc42-WASP interaction is critical for SDF-1–induced chemotaxis of T cells.
The synthetic peptide WKYMVm attenuates the function of the chemokine receptors CCR5 and CXCR4 through activation of formyl peptide receptor-like 1
Authors: Li Bao-Qun , Wetzel Michele A. , Mikovits Judy A. , Henderson Earl E. , Rogers Thomas J. , Gong Wanghua , Le Yingying , Ruscetti Francis W. , Wang Ji Ming
Published: July 2002

The G protein–coupled 7 transmembrane (STM) chemoattractant receptors can be inactivated by heterologous desensitization. Earlier work showed that formly peptide receptor-like 1 (FPRL1), an STM receptor with low affinity for the bacterial chemotactic peptide formyl-methionyl-leucyl-phenylalamine (fMLF), is activated by peptide domains derived from the human immunodeficiency virus (HIV)-1 envelope glycoprotein gp120 and its activation results in desensitization and down-regulation of the chemokine receptors CCR5 and CXCR4 from monocyte surfaces. This study investigated the possibility of interfering with the function of CCR5 or CXCR4 as HIV-1 coreceptors by activating FPRL1. Cell lines were established expressing FPRL1 in combination with CD4/CXCR4 or CD4/CCR5 and the effect of a synthetic peptide, WKYMVm, a potent activator of formyl peptide receptors with preference for FPRL1 was determined. Both CXCR4 and CCR5 were desensitized by activation of the cells with WKYMVm via a staurosporine-sensitive pathway. This desensitization of CXCR4 and CCR5 also attenuated their capacity as the fusion cofactors for HIV-1 envelope glycoprotein and resulted in a significant inhibition of p24 production by cell lines infected with HIV-1 that use CCR5 or CXCR4 as coreceptors. Furthermore, WKYMVm inhibited the infection of human peripheral monocyte–derived macrophages and CD4+ T lymphocytes by R5 or X4 strains of HIV-1, respectively. These results indicate that heterologous desensitization of CCR5 and CXCR4 by an FPRL1 agonist attenuates their major biologic functions and suggest an approach to the development of additional anti-HIV-1 agents.
Adenosine diphosphate strongly potentiates the ability of the chemokines MDC, TARC, and SDF-1 to stimulate platelet function
Authors: Gear Adrian R. L. , Suttitanamongkol Sudawadee , Viisoreanu Delia , Polanowska-Grabowska Renata K. , Raha Sanghamitra , Camerini David
Published: July 2002

Platelet activation is normally induced by primary agonists such as adenosine diphosphate (ADP), thrombin, and collagen, whereas other agonists, such as epinephrine, can play important accessory roles. It is now reported that the macrophage-derived chemokine (MDC), thymus activation–regulated chemokine (TARC), and stromal cell–derived factor one (SDF-1) are highly effective activators of platelet function under a variety of conditions, stimulating platelet shape change, aggregation, and adhesion to collagen or fibrinogen. Chemokine-mediated platelet activation was rapid and maximal (less than 5 seconds) under arterial flow conditions and depended strongly on the presence of low levels of primary agonists such as ADP or thrombin. Concentrations of ADP (0.05-0.25 μM) or thrombin (0.005-0.02 U/mL) that induced minimal aggregation caused major aggregation acting in combination with the chemokines. The ability of apyrase to block chemokine-dependent aggregation or adhesion was consistent with an important role for ADP. Chemokine-stimulated aggregation was also insensitive to indomethacin, suggesting that the activation of cyclo-oxygenase is not involved. TARC, MDC, and SDF-1 increased intracellular calcium concentrations [Ca2+]iwhen combined with low levels of ADP. The MDC and TARC receptor CCR4 was expressed on platelets, and an anti-CCR4 antibody blocked aggregation induced by TARC or MDC. Treatment of platelets with SDF-1 and MDC rapidly exposed P-selectin (CD62P) on the cell surface but did not induce the secretion of serotonin. These findings suggest that the chemokines MDC, TARC, and SDF-1, which may be produced during inflammatory responses, coupled with low levels of ADP or thrombin, can serve as strong stimuli for activating platelet function.
In vitro tumor-pulsed or in vivo Flt3 ligand–generated dendritic cells provide protection against acute myelogenous leukemia in nontransplanted or syngeneic bone marrow–transplanted mice
Authors: Pawlowska Anna B. , Hashino Satoshi , McKenna Hilary , Weigel Brenda J. , Taylor Patricia A. , Blazar Bruce R.
Published: July 2002

To determine whether immune stimulation could reduce acute myelogenous leukemia (AML) lethality, dendritic cells (DCs) were pulsed with AML antigens and used as vaccines or generated in vivo by Flt3 ligand (Flt3L), a potent stimulator of DC and natural killer (NK) cell generation. Mice were then challenged with AML cells. The total number of splenic anti-AML cytotoxic T-lymphocyte precursors (CTLPs) present at the time of challenge was increased 1.9-fold and 16.4-fold by Flt3L or DC tumor vaccines, respectively. As compared with the 0% survival of controls, 63% or more of recipients of pulsed DCs or Flt3L survived long term. Mice given AML cells prior to DC vaccines or Flt3L had only a slight survival advantage versus non-treated controls. NK cells or NK cells and T cells were found to be involved in the antitumor responses of Flt3L or DCs, respectively. DC vaccines lead to long-term memory responses but Flt3L does not. Syngeneic bone marrow transplantation (BMT) recipients were analyzed beginning 2 months post-BMT. In contrast to the uniform lethality in BMT controls given AML cells, recipients of either Flt3L or DC vaccines had a significant increase in survival. The total number of splenic anti-AML CTLPs at the time of AML challenge in BMT controls was 40% of concurrently analyzed non-BMT controls. Flt3L or DC vaccines increased the total anti-AML CTLPs 1.4-fold and 6.8-fold, respectively. Neither approach was successful when initiated after AML challenge. It was concluded that DC vaccines and Flt3L administration can enhance an AML response in non-transplanted or syngeneic BMT mice but only when initiated prior to AML progression.
Autocrine cell suicide in a Burkitt lymphoma cell line (Daudi) induced by interferon α: involvement of tumor necrosis factor as ligand for the CD95 receptor
Authors: Gisslinger Heinz , Kurzrock Razelle , Gisslinger Bettina , Jiang Shuwei , Li Shuren , Virgolini Irene , Woloszczuk Wolfgang , Andreeff Michael , Talpaz Moshe
Published: July 2002

The CD95 receptor, a member of the tumor necrosis factor (TNF) receptor superfamily, mediates signals for cell death on specific ligand or antibody engagement. It was hypothesized that interferon α (IFN-α) induces apoptosis through activation of the CD95-mediated pathway and that CD95 and ligands of the death domain may belong to the group of IFN-stimulated genes. Therefore, the effect of IFN-α on CD95-CD95L expression, on the release of TNF-α, and on TNF receptor 1 expression in an IFN-sensitive human Burkitt lymphoma cell line (Daudi) was investigated. After 5 days' incubation, apoptosis in 81% of IFN-α–treated Daudi cells was preceded by a release of TNF-α and an induction of CD95 receptor expression. Although supernatants of IFN-treated Daudi cells induced apoptosis of CD95-sensitive Jurkat cells, CD95L was undetectable on protein or on messenger RNA levels, and the weak initial expression of TNF receptor 1 increased only slightly during IFN treatment. Surprisingly, binding of TNF-α to CD95 was observed and confirmed by 3 different techniques—enzyme-linked immunosorbent assay using immobilized CD95:Fc–immunoglobulin G, immunoprecipitation assay using CD95 receptor precipitates of Daudi cells, and binding of sodium iodide 125–TNF-α to Daudi cells, which was strongly stimulated by IFN-α and inhibited by CD95L, CD95:Fc, unlabeled TNF-α, and anti–TNF-α antibody. Preincubation of Daudi cells with antagonists of the CD95-mediated pathway resulted in an inhibition of IFN-α–mediated cell death. The present investigation shows that IFN-α induces autocrine cell suicide of Daudi cells by a cross-talk between the CD95 receptor and TNF-α. The CD95 receptor can be considered a third TNF receptor, in addition to p55 and p75.
Identification of novel chemoattractant peptides for human leukocytes
Authors: Bae Yoe-Sik , Bae Hyunjoo , Kim Youndong , Lee Taehoon G. , Suh Pann-Ghill , Ryu Sung Ho
Published: July 2002

Superoxide is the most important armory on the primary defense line of monocytes against invading pathogens, and the identification of new stimuli and the characterization of the regulatory mechanism of superoxide generation are of paramount importance. In this study, we identified 3 novel peptides by screening a synthetic hexapeptide combinatorial library and modification of 1 of the peptides. The isolated peptides that can induce superoxide generation in human monocytes are His-Phe-Tyr-Leu-Pro-Met-CONH2 (HFYLPM), Met-Phe-Tyr-Leu-Pro-Met-CONH2 (MFYLPM), and His-Phe-Tyr-Leu-Pro-D-Met-CONH2 (HFYLPm). All 3 peptides also caused intracellular calcium ([Ca++]i) rise. We tested the specificities of the peptides on cells of different origin by looking at [Ca++]i rise. All 3 peptides acted specifically on leukocytes and not on nonimmune cells. Among leukocytes, HL60 and Jurkat T cells were stimulated specifically by MFYLPM or HFYLPM, respectively. As a physiologic characteristic of the peptides, we observed that all 3 peptides induced chemotactic migration of monocytes. Studying receptor specificity, we concluded that the 3 peptides might act on some shared and some distinct receptor(s) on leukocytes. Studying intracellular signaling set in motion by the peptides revealed that HFYLPM, but not MFYLPM or HFYLPm, induced chemotaxis via phospatidylinositol-3 kinase and protein kinase C. Because HFYLPM, MFYLPM, and HFYLPm not only exhibit different specificities depending on cell type and status of differentiation but also stimulate cells via distinct receptors and signaling, the 3 novel peptides might be useful tools to study leukocyte activation.
Ameliorating effects of fluorocarbon emulsion on sickle red blood cell–induced obstruction in an ex vivo vasculature
Authors: Kaul Dhananjay K. , Liu Xiao-du , Nagel Ronald L.
Published: July 2002

In sickle cell (SS) vaso-occlusion, the culminating event is blockage of blood vessels by sickled red blood cells (SS RBCs). As shown in animal models, SS RBC-induced vaso-occlusion is often partial, allowing for a residual flow, hence oxygen delivery to partially occluded vessels could reduce vaso-occlusion. The efficacy of an oxygenated perflubron-based fluorocarbon emulsion (PFE) was tested for its anti–vaso-occlusive effects in the ex vivo mesocecum vasculature of the rat. Microvascular obstruction was induced by the infusion of deoxygenated SS RBCs into ex vivo preparations with or without pretreatment with platelet-activating factor (PAF). PAF induced enhanced SS RBC–endothelium interactions, leading to greater vaso-occlusion. Microvascular blockage resulted in increased peripheral resistance units (PRU). Deoxygenated SS RBCs caused a persistent 1.5-fold PRU increase in untreated preparations and approximately a 2-fold PRU increase in PAF-treated preparations. The greater PRU in PAF-treated preparations was caused by widespread adhesion and postcapillary blockage. Oxygenated PFE, but not deoxygenated PFE, resulted in PRU decreases to baseline values in both groups of experiments (with or without PAF). The PRU decrease caused by oxygenated PFE infusion was caused by unsickling of SS RBCs in partially occluded vessels, with no antiadhesive effect on already adherent SS RBCs as assessed by intravital microscopy. PFE had no effect on vascular tone. The efficacy of PFE appears to result from its greater capacity to dissolve oxygen (10-fold higher than plasma). The dislodgement of trapped SS RBCs and an increase in wall shear rates will help reverse the partial obstruction. Thus, oxygenated PFE is capable of reducing SS RBC-induced vaso-occlusion, and further development of this approach is advisable.
Functional coupling of FcγRI to nicotinamide adenine dinucleotide phosphate (reduced form) oxidative burst and immune complex trafficking requires the activation of phospholipase D1
Authors: Melendez Alirio J. , Bruetschy Luce , Floto R. Andres , Harnett Margaret M. , Allen Janet M.
Published: July 2002

Immunoglobulin G (IgG) receptors (FcγRs) on myeloid cells are responsible for the internalization of immune complexes. Activation of the oxidase burst is an important component of the integrated cellular response mediated by Fc receptors. Previous work has demonstrated that, in interferon-γ–primed U937 cells, the high-affinity receptor for IgG, FcγRI, is coupled to a novel intracellular signaling pathway that involves the sequential activation of phospholipase D (PLD), sphingosine kinase, and calcium transients. Here, it is shown that both known PLD isozymes, PLD1 and PLD2, were present in these cells. With the use of antisense oligonucleotides to specifically reduce the expression of either isozyme, PLD1, but not PLD2, was found to be coupled to FcγRI activation and be required to mediate receptor activation of sphingosine kinase and calcium transients. In addition, coupling of FcγRI to activation of the nicotinamide adenine dinucleotide phosphate (reduced form) (NADPH) oxidase burst was inhibited by pretreating cells with 0.3% butan-1-ol, indicating an absolute requirement for PLD. Furthermore, use of antisense oligonucleotides to reduce expression of PLD1 or PLD2 demonstrated that PLD1 is required to couple FcγRI to the activation of NADPH oxidase and trafficking of internalized immune complexes for degradation. These studies demonstrate the critical role of PLD1 in the intracellular signaling cascades initiated by FcγRI and its functional role in coordinating the response to antigen-antibody complexes.
Synthetic unmethylated cytosine-phosphate-guanosine oligodeoxynucleotides are potent stimulators of antileukemia responses in naive and bone marrow transplant recipients
Authors: Blazar Bruce R. , Krieg Arthur M. , Taylor Patricia A.
Published: July 2002

Immunostimulatory cytosine-phophate-guanosine (CpG)–containing motifs in bacterial DNA are potent immune system activators. Depending on the bases flanking the CpG motif and on the DNA backbone, CpG oligodeoxynucleotides (ODNs) can induce relatively more B-cell activation or relatively more natural killer (NK)–cell activation. To evaluate their antitumor activities, an NK-optimized ODN (1585) and 2 B-cell–optimized ODNs (1826 and 2006) were compared for their ability to protect naive mice against a lethal acute myelogenous leukemia (AML) challenge. CpG 2006, but not CpG 1585, administered 2 days before the AML challenge, allowed mice to survive more than 100 times a lethal tumor dose. Cell depletion studies showed that protection did not require T or B cells but depended on NK cells and also on an NK-independent mechanism. CpG 2006 protected against AML challenge in both syngeneic and allogeneic bone marrow transplant (BMT) recipients at both early and late time points after transplantation. Although CpG 1585 had no protective effect on its own, it showed a striking synergy with CpG 2006 to induce prolonged survival to AML challenge in allogeneic recipients of T-cell–depleted marrow grafts, exceeding the survival benefit of donor lymphocyte infusion (DLI). When combined with DLI, a synergistic effect was observed in recipients of CpG2006 or 2006 + 1585 with 88% of mice surviving long-term. These data are the first to indicate that the systemic administration of CpG ODNs is a potent means of inducing therapeutic anti-AML innate immune responses in naive and BMT recipients.
Lipopolysaccharide activation of the MEK-ERK1/2 pathway in human monocytic cells mediates tissue factor and tumor necrosis factor α expression by inducing Elk-1 phosphorylation and Egr-1 expression
Authors: Guha Mausumee , O'Connell Maria A. , Pawlinski Rafal , Hollis Angela , McGovern Patricia , Yan Shi-Fang , Stern David , Mackman Nigel
Published: July 2002

Lipopolysaccharide (LPS) induces human monocytes to express many proinflammatory mediators, including the procoagulant molecule tissue factor (TF) and the cytokine tumor necrosis factor alpha (TNF-α). The TF and TNF-α genes are regulated by various transcription factors, including nuclear factor (NF)-κB/Rel proteins and Egr-1. In this study, the role of the MEK-ERK1/2 mitogen-activated protein kinase (MAPK) pathway in LPS induction of TF and TNF-α gene expression in human monocytic cells was investigated. The MAPK kinase (MEK)1 inhibitor PD98059 reduced LPS induction of TF and TNF-α expression in a dose-dependent manner. PD98059 did not affect LPS-induced nuclear translocation of NF-κB/Rel proteins and minimally affected LPS induction of κB-dependent transcription. In contrast, PD98059 and dominant-negative mutants of the Ras-Raf1-MEK-ERK (extacellular signal–regulated kinase) pathway strongly inhibited LPS induction of Egr-1 expression. In kinetic experiments LPS induction of Egr-1 expression preceded induction of TF expression. In addition, mutation of the Egr-1 sites in the TF and TNF-α promoters reduced expression of these proinflammatory genes. It was demonstrated that LPS induction of the Egr-1 promoter was mediated by 3 SRE sites, which bound an LPS-inducible complex containing serum response factor and Elk-1. LPS stimulation transiently induced phosphorylation of Elk-1 and increased the functional activity of a GAL4–Elk-1TA chimeric protein via the MEK-ERK1/2 pathway. The data indicate that LPS induction of Egr-1 gene expression is required for maximal induction of the TNF-α and TF genes in human monocytic cells.
Targeted deletion of 5′HS1 and 5′HS4 of the β-globin locus control region reveals additive activity of the DNaseI hypersensitive sites
Authors: Bender M. A. , Roach Julia N. , Halow Jessica , Close Jennie , Alami Raouf , Bouhassira Eric E. , Groudine Mark , Fiering Steven N.
Published: July 2002

The mammalian β-globin locus is a multigenic, developmentally regulated, tissue-specific locus from which gene expression is regulated by a distal regulatory region, the locus control region (LCR). The functional mechanism by which the β-globin LCR stimulates transcription of the linked β-like globin genes remains unknown. The LCR is composed of a series of 5 DNaseI hypersensitive sites (5′HSs) that form in the nucleus of erythroid precursors. These HSs are conserved among mammals, bind transcription factors that also bind to other parts of the locus, and compose the functional components of the LCR. To test the hypothesis that individual HSs have unique properties, homologous recombination was used to construct 5 lines of mice with individual deletions of each of the 5′HSs of the endogenous murine β-globin LCR. Here it is reported that deletion of 5′HS1 reduces expression of the linked genes by up to 24%, while deletion of 5′HS4 leads to reductions of up to 27%. These deletions do not perturb the normal stage-specific expression of genes from this multigenic locus. In conjunction with previous studies of deletions of the other HSs and studies of deletion of the entire LCR, it is concluded that (1) none of the 5′HSs is essential for nearly normal expression; (2) none of the HSs is required for proper developmental expression; and (3) the HSs do not appear to synergize either structurally or functionally, but rather form independently and appear to contribute additively to the overall expression from the locus.
Human herpesvirus 7 induces the functional up-regulation of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) coupled to TRAIL-R1 down-modulation in CD4+ T cells
Authors: Secchiero Paola , Mirandola Prisco , Zella Davide , Celeghini Claudio , Gonelli Arianna , Vitale Marco , Capitani Silvano , Zauli Giorgio
Published: July 2002

Human herpesvirus 7 (HHV-7) is endemic in the adult human population. Although HHV-7 preferentially infects activated CD4+ T lymphocytes, the consequence of T-cell infection for viral pathogenesis and immunity are still largely unknown. HHV-7 infection induces apoptosis mostly in uninfected bystander cells but not in productively infected CD4+ T cells. To dissect the underlying molecular events, the role of death-inducing ligands belonging to the tumor necrosis factor (TNF) cytokine superfamily was investigated. HHV-7 selectively up-regulated the expression of TNF-related apoptosis-inducing ligand (TRAIL), but not that of CD95 ligand or TNF-α in lymphoblastoid (SupT1) or primary activated CD4+ T cells. Moreover, in a cell-to-cell-contact assay, HHV-7–infected CD4+ T lymphocytes were cytotoxic for bystander uninfected CD4+ T cells through the TRAIL pathway. By contrast, HHV-7 infection caused a marked decrease of surface TRAIL-R1, but not of TRAIL-R2, CD95, TNF-R1, or TNF-R2. Of note, the down-regulation of TRAIL-R1 selectively occurred in cells coexpressing HHV-7 antigens that became resistant to TRAIL-mediated cytotoxicity. These findings suggest that the TRAIL-mediated induction of T-cell death may represent an important immune evasion mechanism of HHV-7, helping the virus to persist in the host organism throughout its lifetime.
Novel triterpenoid CDDO-Me is a potent inducer of apoptosis and differentiation in acute myelogenous leukemia
Authors: Konopleva Marina , Tsao Twee , Ruvolo Peter , Stiouf Irina , Estrov Zeev , Leysath Clinton E. , Zhao Shourong , Harris David , Chang Shirong , Jackson C. Ellen , Munsell Mark , Suh Nanjoo , Gribble Gordon , Honda Tadashi , May W. Stratford , Sporn Michael B. , Andreeff Michael
Published: July 2002

It has been shown that the novel synthetic triterpenoid CDDO inhibits proliferation and induces differentiation and apoptosis in myeloid leukemia cells. In the current study the effects of the C-28 methyl ester of CDDO, CDDO-Me, were analyzed on cell growth and apoptosis of leukemic cell lines and primary acute myelogenous leukemia (AML). CDDO-Me decreased the viability of leukemic cell lines, including multidrug resistant (MDR)-1–overexpressing, p53null HL-60-Dox and of primary AML cells, and it was 3- to 5-fold more active than CDDO. CDDO-Me induced a loss of mitochondrial membrane potential, induction of caspase-3 cleavage, increase in annexin V binding and DNA fragmentation, suggesting the induction of apoptosis. CDDO-Me induced pro-apoptotic Bax protein that preceded caspase activation. Furthermore, CDDO-Me inhibited the activation of ERK1/2, as determined by the inhibition of mitochondrial ERK1/2 phosphorylation, and it blocked Bcl-2 phosphorylation, rendering Bcl-2 less anti-apoptotic. CDDO-Me induced granulo-monocytic differentiation in HL-60 cells and monocytic differentiation in primary cells. Of significance, colony formation of AML progenitors was significantly inhibited in a dose-dependent fashion, whereas normal CD34+ progenitor cells were less affected. Combinations with ATRA or the RXR-specific ligand LG100268 enhanced the effects of CDDO-Me on cell viability and terminal differentiation of myeloid leukemic cell lines. In conclusion, CDDO-Me is an MDR-1– and a p53-independent compound that exerts strong antiproliferative, apoptotic, and differentiating effects in myeloid leukemic cell lines and in primary AML samples when given in submicromolar concentrations. Differential effects of CDDO-Me on leukemic and normal progenitor cells suggest that CDDO-Me has potential as a novel compound in the treatment of hematologic malignancies.
Proteins encoded by genes involved in chromosomal alterations in lymphoma and leukemia: clinical value of their detection by immunocytochemistry
Authors: Falini Brunangelo , Mason David Y.
Published: July 2002

Acquired chromosomal anomalies (most commonly translocations) in lymphoma and leukemia usually result in either activation of a quiescent gene (by means of immunoglobulin or T-cell–receptor promotors) and expression of an intact protein product, or creation of a fusion gene encoding a chimeric protein. This review summarizes current immunocytochemical studies of these 2 categories of oncogenic protein, with emphasis on the clinical relevance of their detection in diagnostic samples. Among the quiescent genes activated by rearrangement, expression of cyclin D1 (due to rearrangement of theCCND1 [BCL-1] gene) is a near-specific marker of t(11;14) in mantle cell lymphoma; BCL-2 expression distinguishes follicular lymphoma cells from their nonneoplastic counterparts in reactive germinal centers and appears to be an independent prognostic marker in diffuse large cell lymphoma; andTAL-1 (SCL) expression identifies T-cell acute lymphoblastic neoplasms in which this gene is activated. The protein products of other genes activated by chromosomal rearrangement have a role as markers of either lineage (eg, PAX-5 [B-cell–specific activator protein] for B cells, including B-lymphoblastic neoplasms), or maturation stage (eg, BCL-6 for germinal-center and activated B cells and MUM-1/IRF4 for plasma cells). Currently, no hybrid protein encoded by fusion genes is reliably detectable by antibodies recognizing unique junctional epitopes (ie, epitopes absent from the wild-type constituent proteins). Nevertheless, staining for promyelocytic leukemia (PML) protein will detect acute PML with t(15;17) because the microspeckled nuclear labeling pattern for PML-RARα is highly distinctive. Similarly, antibodies to the anaplastic lymphoma kinase (ALK) tyrosine kinase are valuable (because wild-type ALK is not found in normal lymphoid tissue) in detecting neoplasms (CD30-positive large T-cell lymphomas) with t(2;5) or its variants. Thus, immunocytochemical detection of the products of many rearranged genes in lymphoma and leukemia can be clinically informative and provide information on cellular and subcellular protein expression that cannot be inferred from studies based on messenger RNA.
Treatment Outcome and Survival Associated With Metastatic Renal Cell Carcinoma of Non–Clear-Cell Histology
Authors: Motzer Robert J. , Bacik Jennifer , Mariani Tania , Russo Paul , Mazumdar Madhu , Reuter Victor
Published: July 2002

PURPOSE: To define outcome data for patients with metastatic renal cell carcinoma (RCC) with histology other than clear-cell type, including collecting duct (or medullary carcinoma), papillary, chromophobe, and unclassified histologies.

PATIENTS AND METHODS: Sixty-four patients with metastatic non–clear-cell RCC histology were the subjects of this retrospective review. Included in the analysis were 22 (8%) of 286 patients from a clinical trials database, 19 of 1,166 patients from a surgery database, and 23 of 357 patients from a pathology database.

RESULTS: The prevalent histology was collecting duct, present in 26 (41%) patients. The number of patients with chromophobe and papillary histologies was 12 (19%) and 18 (28%), respectively. Eight (12%) of the patients had tumors that could not be classified for specific tumor histology. Among the 43 patients treated with 86 systemic therapies, including 37 cytokine therapies, two patients (5%) were observed to have a partial response. The median overall survival time was 9.4 months (95% confidence interval, 8 to 14 months). The survival was longer for patients with chromophobe tumors compared with collecting duct or papillary histology, and this group included four patients with survival of greater than 3 years.

CONCLUSION: RCC consists of a heterogeneous group of tumors including clear-cell, papillary, chromophobe, collecting duct, and unclassified cell types. Non–clear-cell histologies constitute less than 10% of patients in general populations of patients with advanced RCC treated on clinical trials. Metastatic non–clear-cell RCC is characterized by a resistance to systemic therapy and poor survival, with the survival for patients with chromophobe tumors longer than that for patients with metastatic collecting duct or papillary RCC. Treatment with novel agents on clinical trials is warranted.
Knockdown of RFC4 inhibits cell proliferation of oral squamous cell carcinoma in vitro and in vivo
Authors: You Pengyue , Wang Di , Liu Zheng , Guan Shuzhen , Xiao Ning , Chen Haotian , Zhang Xin , Wu Lichuan , Wang Guizhen , Dong Haitao
Published: December 2024

Oral squamous cell carcinoma (OSCC) is the one of the most common types of malignant tumor found in the head and neck area. Replication factor C subunit 4 (RFC4), an oncogene active in various human cancers, has been rarely studied in OSCC. In the present study, bioinformatics analysis identified RFC4 as a potential key target in OSCC progression. Additional experiments showed that RFC4 expression was significantly higher in OSCC tumor tissues than in normal tissues. Knockdown of RFC4 led to G2/M phase cell cycle arrest and inhibited the proliferation of OSCC cells both in vitro and in vivo. High RFC4 expression in OSCC tumors was linked to increased levels of MET, along with reduced levels of CD274 and CD160. Overall, the present study reveals that RFC4 may play a pivotal role in OSCC tumorigenesis and could serve as a potential predictive marker for the efficacy of immunotherapy.
An investigation of the effect of vibration duration on the evaluation of subjective responses to horizontal vibration
Authors: Hayashi Kentaro , Matsumoto Yasunao , Yokoshima Shigenori , Higashida Toyohiko
Published: December 2024

A laboratory experiment was conducted to investigate an evaluation method for building habitability based on subjective responses to vibrations caused by external sources. Twenty‐five individuals participated in the experiment, which involved 76 input stimulus conditions, including vibrations based on field records and sinusoidal vibrations in the horizontal direction. Subjective responses were measured in terms of “magnitude,” “concern,” and “discomfort,” The study compared several domestic and international evaluation methods for environmental vibrations with subjective responses, revealing that the vibration dose value, which accounts for the effect of vibration duration raised to the fourth power, was the most reasonable method.
Clinical validation of MR‐generated synthetic CT by MRCAT for brain tumor radiotherapy
Authors: Yip Tyrone Tsz Yeung , Li Zhichun , Li Tian
Published: December 2024

Objective

MRI is an emerging modality in radiotherapy (RT). Accuracy synthetic CT is the prerequisite for implementing MR‐only RT planning. This study validated the commercial algorithm of MR for calculating attenuation (MRCAT) in terms of image quality and dosimetric agreement.

Methods

Brain tumor cases with 18 treated using intensity‐modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT), and 15 treated using stereotactic radiosurgery (SRS) were analyzed. Synthetic CTs were resampled referencing planning CT. Treatment plan calculated on planning CT was recalculated on resampled MRCAT. Image quality of selected metrics and dosimetric agreements were assessed by dose‐volume‐histogram and 3D gamma analysis.

Results

For IMRT/VMAT and SRS cases, mean error were 23.42 ± 1.05 and 28.39 ± 3.17 HU; mean absolute error were 38.03 ± 1.42 and 52.36 ± 2.63 HU; root mean squared error were 89.09 ± 6.65 and 108.38 ± 12.23 HU; peak signal‐to‐noise ratio were 29.11 ± 0.60  and 27.65 ± 0.59 dB; and structural similarity index measures were 0.88 ± 0.00 and 0.70 ± 0.01 respectively. No significant differences were identified for DVH metrics accounting the target coverage. Most OARs did not have significant dose deviation, except left lens with 0.70% higher in D‐mean after recalculation (p < 0.001). For criteria of 3 mm/3%, 2 mm/2%, and 1 mm/1%, gamma passing rates for IMRT/VMAT were 99.92%, 99.42%, and 96.47%, while SRS were 99.86%, 99.52%, and 97.57% respectively. Correlation between passing rate and image quality metrics was established in IMRT/VMAT cases, with higher similarity yield better dosimetric agreement between planning and synthetic CT.

Conclusion

This study has validated the MRCAT for clinical use in terms of comparable image quality and dosimetric agreement with planning CT. Further case selection and MR‐compatible immobilization device would be required.
On the Stability Verification of Adaptive Uncertain and Coupled Dynamical Discrete‐Time Systems
Authors: Kurttisi Atahan , Aly Islam A. , Dogan K. Merve
Published: December 2024

In the controlled uncertain coupled dynamical systems employing standard model reference adaptive methods, stability is guaranteed either under minimally coupled dynamics or negligible system uncertainties. Thus, significant uncertainties and coupled dynamics in an uncertain system can lead to instability. In recent papers, continuous‐time adaptive architectures are derived to compensate for uncertainties and coupled dynamics together. However, discretizing such algorithms doesn't guarantee the stability of the system directly since it complicates the Lyapunov analysis in discrete‐time. This makes it challenging to generalize successful continuous‐time adaptive control results to discrete‐time environments. Thus, this article includes the stability verification for adaptive uncertain and coupled dynamical discrete‐time systems and shows the efficacy of the novel controller over the standard ones through two illustrative examples.
Electron‐Beam‐Induced Adatom‐Vacancy‐Complexes in Mono‐ and Bilayer Phosphorene
Authors: Speckmann Carsten , Angeletti Andrea , Kývala Lukáš , Lamprecht David , Herterich Felix , Mangler Clemens , Filipovic Lado , Dellago Christoph , Franchini Cesare , Kotakoski Jani
Published: December 2024

Phosphorene, a puckered 2D allotrope of phosphorus, has sparked considerable interest in recent years due to its potential especially for optoelectronic applications with its layer‐number‐dependant direct band gap and strongly bound excitons. However, detailed experimentalcharacterization of its intrinsic defects as well as its defect creation characteristics under electron irradiation are scarce. Here, the creation and stability of a variety of defect configurations under 60 kV electron irradiation in mono‐ and bilayer phosphorene are reported including the first experimental reports of stable adatom‐vacancy‐complexes. Displacement cross section measurements in bilayer phosphorene yield a value of 7.7 ± 1.4 barn with an estimated lifetime of adatom‐vacancy‐complexes of 19.9 ± 0.7 s, while some are stable for up to 68 s under continuous electron irradiation. Surprisingly, ab initio‐based simulations indicate that the complexes should readily recombine, even in structures strained by up to 3%. The presented results will help to improve the understanding of the wide variety of defects in phosphorene, their creation, and their stability, which may enable new pathways for defect engineered phosphorene devices.
Textile Electrodes for Electrocardiogram Monitoring
Authors: Zhou Wen , Zhang Lu , Zhang Jichao , Fu Shaohai
Published: December 2024

Electrocardiogram (ECG) monitoring is crucial for early diagnosis and timely treatment of cardiovascular diseases which are the major cause of global death, and it is of great significance but a long‐standing challenge to acquire the stability of signal quality while maintaining high comfort during ECG monitoring over a long time. Textile electrodes offer strong potential for applications in the long‐term monitoring of ECG signals due to gel‐free and dry characteristics compared with existing wet silver/silver chloride (Ag/AgCl) gelled electrodes. Therefore, the last few years have witnessed the rapid development of textile ECG electrodes which are further accelerated by the booming researches on wearable electronics. Herein, a review of recent advances in textile electrodes for ECG monitoring with a focus on advanced material designs and construction technologies is presented. First, comprehensive considerations of ECG monitoring with textile electrodes are provided. Subsequently, the fabrication technologies for high‐performance textile ECG electrodes are highlighted. Finally, particular emphases are placed on the current challenges and future opportunities of textile electrodes for ECG monitoring.
Terahertz Metamaterial Sensors: Design Theory, Optimization Approach, and Advancements in Biosensing Applications
Authors: Cao Lei , Jia Shanshan , Meng Fanqi , Richter Merle , Loth Yannik , Wigger Anna Katharina , Yang Chenglin , Zhang Liuyang , Bolívar Peter Haring , Roskos Hartmut G.
Published: December 2024

Metamaterials (MMs), distinguished by their unique electromagnetic properties, offer significant advantages in the realm of terahertz (THz) biosensing and early disease diagnosis. The intense electric field confined within subwavelength volumes in metallic MMs enhances the interaction between light and analytes. The Q‐factor, sensitivity and figure of merit (FOM) are three critical direct parameters for quantitative evaluation of sensor performance. Researchers are pursuing enhancement of these parameters by optimal design of MMs structures and dimensions as well as proper choice of materials. Recently, dielectric perturbation theory is quantitatively calculated and successfully utilized in the design and optimization of THz MMs sensors. Guided by this theory, this review focuses on the design principle of THz MMs sensors, the various study on how to improve the fundamental parameters of THz MMs sensors, the specific application in biosensing including the functionalization process, and the fabrication of THz MMs sensors. Based on these methods and results, the future development of THz sensors is finally presented in a perspective view.
Significantly Enhanced Piezoelectricity of Poly(Vinylidene Fluoride) via Orienting Nanobound State Ions
Authors: Ye Zhiwei , Yi Juan , Zhang Yibo , Xiong Chuanxi
Published: December 2024

Poly(vinylidene fluoride) (PVDF) demonstrates great potential for applications in flexible sensing and energy harvesting but the piezoelectric coefficient is less than 30 pm V−1 even with the full beta phase. Herein, an all‐organic composite of PVDF with ionic liquid (IL) is manufactured through stretching, constrained annealing, and polarization. The DFT and XPS indicate strong ionic dipole interactions between PVDF and IL, favoring the orientation and crystallization of PVDF. Surprisingly, the nanobound states ions achieve orientation in different physical fields, providing ionic dipole enhances the piezoelectricity of the composite films, confirmed by variable temperature dielectric properties, FTIR and XRD. An inverse piezoelectric coefficient of 51.8 pm V−1, obtained from PVDF containing 0.75 wt.% IL, improved by 116% compared to commercial PVDF (≈24 pm V−1). This work presents a novel composite strategy for the fabrication of high piezoelectric flexible polymers.
Nano‐Micro Granular Ink with Modulatable Structure and Function Modules for Wound Dressing Preparation via 3D Printing
Authors: Wang Tao , Niu Dawei , Fang Haowei , Pan Haiyang , Zhang Kunxi , Cui Haiyan
Published: December 2024

For porous dressing production through 3D printing, it is challenging to adjust the printability of ink while balancing its bioactivity. The present study introduces an example of a modular construction method for heterogeneous granular ink. Gelatin microspheres (gelatin‐MSs) are assembled by poly (gallic acid)‐coated zinc‐containing nano‐hydroxyapatite (ZnHA‐NP/p(GA)), and further cooperate with Ag+ to form a kind of granular inks. The three modules including gelatin‐MS, ZnHA‐NP/p(GA), and Ag have their own functions: The viscoelastic gelatin‐MS module is the essential component that realizes ink extrusion. The ZnHA‐NP/p(GA) module not only forms reversible interactions with gelatin‐MS that realize the assembly but also takes the responsibility of reactive oxygen species‐scavenging and anti‐inflammatory. The Ag module not only interacts with ZnHA‐NP/p(GA) module to promote the stability but also exhibits strong antibacterial property. The gelatin‐MS size, p(GA)‐coating duration, ZnHA‐NP/p(GA) content, and Ag content are optimized to yield a nano‐micro granular ink for bioactive porous dressing preparation that is used to significantly promote the healing of refractory wounds. Therefore, this method allows particles with different structures and bio‐functions that serve as modules to assemble into inks, realizing the balance of printability and biological functions for dressing manufacturing.