bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Trichoderma virens and Burkholderia cepacia for antagonistic activity against root-knot nematode, Meloidogyne incognita
Authors: Massoud Samia , Meyer Susan L.F. , Roberts Daniel , Chitwood David
Published: July 2002

The bacterium Burkholderia cepacia (strain Bc-2) and the fungus Trichoderma virens (strain Gl-3) were investigated for activity against the nematode Meloidogyne incognita. Culture filtrates from Bc-2 and Gl-3 contained extracellular factors that inhibited egg hatch and second-stage juvenile (J2) mobility. Size fractionation results and lack of detectable chitinase or protease activities from Bc-2 and Gl-3 culture filtrates suggested that the inhibitory factors in the in vitro assays were non-enzymic. Tomato root explant cultures of M. incognita treated with T.virens culture filtrate had 42% fewer eggs and J2 per g of roots than cultures treated with control medium that had not been inoculated with T. virens. In glasshouse tests with tomato, Bc-2 and Gl-3 were applied individually as seed coatings and as root drenches in both viable and non-viable formulations. At the 65-day harvest, non-viable B. cepacia was the only treatment that suppressed eggs and J2 per g of roots (29% suppression) compared to water controls. Evaluation de l'activité antagoniste de Trichoderma virens et Burkholderia cepacia envers le nématode Meloidogyne incognita - La bactérie Burkholderia cepacia (souche Bc-2) et le champignon Trichoderma virens (souche G1-3) ont été étudiés dans l'optique de leur action envers le nématode Meloidogyne incognita. Les filtrats de culture de Bc-2 et de G1-3 contiennent des facteurs extracellulaires inhibant l'éclosion et la motilité des juvéniles de deuxième stade (J2) du nématode. Les résultats de fractionnements relatifs à la taille et la nondétection d'une activité chitinasique ou protéasique dans les filtrats de culture de Bc-2 et G1-3 suggèrent que les facteurs inhibant présents lors des expériences in vitro ne sont pas de nature enzymatique. Des élevages de M. incognita sur explants de racines de tomate traités avec des filtrats de culture de T. virens produisent des oeufs et des J2 en nombre inférieur de 42% à celui d'élevages traités par un milieu témoin, non inoculé avec T. virens. Lors d'essais en serre sur tomate, Bc-2 et G1-3 ont été appliqués séparément, soit en pralinage des semences, soit sur la tranchée, et en formulation vivante ou non-vivante. A la récolte, après 65 jours, la formulation non-vivante de B. cepacia s'est révélée le seul traitement diminuant le nombre d'oeufs et de J2 par g de racines: moins 29% par rapport au témoin ne contenant que de l'eau.
Mixed-layer kaolinite-illite-vermiculite in North Sea shales
Authors: Sakharov B. A. , Lindgreen H. , Salyn A. L. , Drits V. A.
Published: July 2002

The finest fractions of Upper Jurassic shales from the North Sea and onshore Denmark contain 80–90% of an illite-smectite-vermiculite (I-S-V) mixed-layer mineral and, in addition a phase which has X-ray diffraction (XRD) peaks at 7.20–7.26 Å and 3.56–3.58 Å in air- dried and glycolated specimens. This phase may be a fine kaolinite with a small thickness of coherent scattering domains (CSDs) or alternatively a mixed-layer mineral which has kaolinite as the dominant component. For one sample from the Norwegian well 9/4-3, these alternatives are investigated using the multi-specimen method by which agreement between the experimental pattern and the pattern calculated for one and the same structure is obtained for each of several specimens saturated with different cations and with/without glycolation. It is demonstrated that the modelled XRD patterns for a kaolinite-illite-vermiculite (K-I-V) structure having 0.94 kaolinite, 0.03 illite and 0.03 vermiculite layers and random alternation fit the experimental patterns.
Adsorption of silane coupling agents onto kaolinite surfaces
Authors: Johansson U. , Holmgren A. , Forsling W. , Frost R. L.
Published: July 2002

The adsorption of the silane coupling agents N-(2-amino-ethyl)-3-aminopropyl- trimethoxysilane (Z-6020), N-(2-(vinylbenzyl-amino)-ethyl)-3-amino-propyl-trimethoxysilane (Z-6032) and 3-glycidoxy-propyl-trimethoxysilane (Z-6040) onto the surface of kaolinite has been studied using the solvents water and ethanol. The adsorbed silanes were analysed using diffuse reflectance Fourier transform infrared (DRIFT) spectroscopy and FT-Raman spectroscopy. When the silane coupling agents are dissolved in water, silanol groups are formed. Raman spectra of aqueous solutions of the silanes show that condensation of the silanols into oligomers occurred. The peak at 1000 cm-1 assigned to Si–O–Si vibrations indicates that polymerization has occurred. A similar behaviour is observed when the silanes are dissolved in ethanol. The DRIFT spectra show that the silane coupling agents adsorb onto the surface of kaolinite. It is proposed that the oligomers are bonded to the kaolinite surface only by hydrogen bondings with no covalent bonds formed.
Late-orogenic alpine-type (apatite)-quartz fissure vein mineralization in the Rheinisches Schiefergebirge, NW Germany: mineralogy, formation conditions and lateral-secretionary origin
Authors: Wagner T. , Cook N. J.
Published: July 2002

Mineralogical, geochemical and fluid inclusion investigations of a representative suite of fissure vein mineralizations in the Rheinisches Schiefergebirge, NW Germany indicate a link to the latest stage of the Variscan orogenic evolution. Model P-T-conditions during initiation of fibrous fissure vein quartz growth are in the range 370–420°C at 0.2–0.7 kbar. The dataset suggests significant fluid cooling during evolution of the vein systems. Minimum temperatures at the end of fibrous quartz growth lie in the range 140–190°C, with conductive heat transfer and heat consumption during interaction with wallrock believed to be the main mechanisms responsible. Wallrock alteration is characterized by leaching and mobilization of most of the dominant vein components (quartz, albite, apatite), notably Si, Na and P. The principal stage of vein formation is, on the basis of available data, believed to relate to a process of intra-formational redistribution or lateral secretion. However, part of those elements deposited both in wallrock and fissure veins were probably supplied directly by the external fluid. Rates of fissure opening and material deposition were in equilibrium during the principal growth stage of fibrous quartz. However, this situation evolved due to a slowing down of material supply and deposition coupled with an increased rate of fissure opening to produce open fissures and formation of idiomorphic quartz crystals within them. Deposition depths were in the range of 0.6–2.1 km, appreciably lower than estimations of overburden. We believe therefore that formation of the fissure vein systems took place along the retrograde late–orogenic exhumation path, in a transitional stage between Variscan collision and a late- to post-orogenic extensional regime. Fluid composition characteristics also strongly suggest a relationship to the latest stages of the Variscan mineralization cycle in which low–salinity brines dominate. Development of fissure vein systems during the latest stages of continental collision, identified here from the Variscan orogeny, can be considered analogous with similar phenomena in the Alpine orogenic belt.
Petrography and mineral chemistry of mantle xenoliths in a carbonate-rich melilititic tuff from Mt. Vulture volcano, southern Italy
Authors: Jones A. P. , Kostoula T. , Stoppa F. , Woolley A. R.
Published: July 2002

We present petrographic and mineralogical data for 21 mantle xenoliths (12 lherzolites, 8 wehrlites and 1 composite) selected from a suite of more than 70 samples collected from the Monticchio Formation, Mt. Vulture volcano, southern Italy. The xenoliths are rounded, coarse- to porphyroclastic-textured, and very fresh, with the following equilibrated mineral assemblages; olivine (Fo90–92), orthopyroxene (∼En89, Wo2.0), clinopyroxene (Mg90–92, 3–6% Al2O3, 1–1.5% Cr2O3), and chrome-spinel (14–20% MgO, ∼30–40% Cr2O3). Many xenoliths contain partial melt glasses and accessory sulphide (pentlandite) Some contain primary mica (phlogopite with ∼4% FeO, 1.8% Cr2O3, 1.4–2.8% TiO2) with slightly zoned rims (Fe-, Ti-, Al-enriched). One contains relics of garnet (pyrope; Mg84). Secondary veins in several xenoliths contain carbonate with significant Sr levels (∼0.5–1.0% SrO), occasional apatite and scarce melanite, all typical of carbonatites and presumably related to the host magma (melilitite/carbonatite). Although amphibole is a common megacryst in the same volcanic units, no primary amphibole was found in the xenoliths themselves. Calculated pressures and temperatures using a range of geothermometers/barometers give values of 14–22 kbar and 1050–1150°C. In particular, the En-Sp and Di-Sp thermo/barometers (Mercier, 1980) show a good positive correlation between P and T. The Monticchio xenoliths lie on the high-T side of an ‘oceanic’ geotherm. The xenolith geotherm is hotter than general heat flow values in this region at the current day (50 mWm−2) but it compares well with the high-pressure end of a typical alkaline continental rift.
Synneusis of zircon: why not?
Authors: Alexandrov P.
Published: July 2002

Some zircons from the Hercynian Soultz granite, NE France, exhibit complex structures, with double cores and oscillatory-banded overgrowths. These glomeroporphyritic crystals are uncommon for zircons, in which synneusis has not previously been described. The cores of the zircons are considered to correspond to very quickly formed {100} or {110} prisms. These could slowly sediment in the magma chamber and cluster together while sinking. The overgrowth rims correspond to a slower growth rate.

U/Pb ion-probe dating of the cores and the overgrowth rims provided the same age of 327±6 Ma. Chemical electron microprobe analyses indicated that cores and rims have the same composition for major and trace elements.

The sinking of zircons accounts for the abnormally high percentages of zircon in the lower parts of the granite. The formation of clusters in the early stages of crystallization needs stableP/Tconditions, a hot, liquid silicate melt with a high fluid content, and no other minerals crystallizing (liquidus phase).
Enhanced survival in Sandhoff disease mice receiving a combination of substrate deprivation therapy and bone marrow transplantation
Authors: Jeyakumar Mylvaganam , Norflus Francine , Tifft Cynthia J. , Cortina-Borja Mario , Butters Terry D. , Proia Richard L. , Perry V. Hugh , Dwek Raymond A. , Platt Frances M.
Published: July 2002

Sandhoff disease is a lysosomal storage disorder characterized by GM2 ganglioside accumulation in the central nervous system (CNS) and periphery. It results from mutations in the HEXB gene, causing a deficiency in β-hexosaminidase. Bone marrow transplantation (BMT), which augments enzyme levels, and substrate deprivation (using the glycosphingolipid biosynthesis inhibitor N-butyldeoxynojirimycin [NB-DNJ]) independently have been shown to extend life expectancy in a mouse model of Sandhoff disease. The efficacy of combining these 2 therapies was evaluated. Sandhoff disease mice treated with BMT and NB-DNJ survived significantly longer than those treated with BMT or NB-DNJ alone. When the mice were subdivided into 2 groups on the basis of their donor bone marrow–derived CNS enzyme levels, the high enzyme group exhibited a greater degree of synergy (25%) than the group as a whole (13%). Combination therapy may therefore be the strategy of choice for treating the infantile onset disease variants.
Prostaglandin E2 is a selective inducer of interleukin-12 p40 (IL-12p40) production and an inhibitor of bioactive IL-12p70 heterodimer
Authors: Kaliński Paweł , Vieira Pedro L. , Schuitemaker Joost H. N. , de Jong Esther C. , Kapsenberg Martien L.
Published: July 2002

Interleukin-12 p70 (IL-12p70) heterodimer, composed of p35 and p40 subunits, is a major Th1-driving cytokine, promoting cell-mediated immunity. In contrast, IL-12p40 homodimer, secreted by APC in the absence of p35 expression, and free p40 monomer do not mediate IL-12 activity but act as IL-12 antagonists. Here it is reported that prostaglandin E2 (PGE2), an inflammatory mediator with a previously known Th2-driving function, dose-dependently enhances the IL-12p40 mRNA expression and the secretion of IL-12p40 protein in human tumor necrosis factor-alpha (TNFα)–stimulated immature dendritic cells (DCs). This effect is selective and is not accompanied by the induction of IL-12p35 expression or by secretion of IL-12p70 heterodimer. Inability of TNFα/PGE2 to induce IL-12p70 was not compensated by interferon gamma (IFNγ), which strongly enhanced the lipopolysaccharide (LPS)–induced IL-12p70 production. In addition to the selective induction of IL-12p40 in TNFα-stimulated DCs, PGE2 inhibited the production of IL-12p70 and IL-12p40 in DCs stimulated with LPS or CD40 ligand. These data suggest an additional level of the Th2-promoting activity of PGE2, via selective induction of IL-12p40. Selective induction of IL-12p40 and suppression of bioactive IL-12p70 may have negative impact on anticancer vaccination with PGE2-matured DCs.
A homologous naturally occurring mutation in Duffy and CCR5 leading to reduced receptor expression
Authors: Tamasauskas Daniel , Powell Vivien , Saksela Kalle , Yazdanbakhsh Karina
Published: July 2002

Genetic variations in the CC chemokine receptor (CCR5) leading to reduced or absent expression are associated with resistance to human immunodeficiency virus infection and delayed onset of acquired immunodeficiency syndrome. Similarly, lack of the red-cell chemokine receptor Duffy confers protection against malarial infection byPlasmodium vivax. Investigators have previously described a missense mutation (R89C) in the first intracellular loop of Duffy that results in reduced protein expression. The present study shows that the lower Duffy expression is due to loss of the positive charge at this position, resulting in protein instability. Moreover, R60S, a mutation in the first intracellular loop of CCR5 noted in a recent cohort study, likewise results in reduced surface expression and function of CCR5. The presence of a homologous, naturally occurring mutation that may be protective against disease thus defines a novel mechanism accounting for the decreased expression of these receptors in some individuals.
The adapter protein CrkL associates with CD34
Authors: Felschow Donna M. , McVeigh Megan L. , Hoehn Gerard T. , Civin Curt I. , Fackler Mary Jo
Published: July 2002

CD34 is a cell-surface transmembrane protein expressed specifically at the stem/progenitor stage of lymphohematopoietic development that appears to regulate adhesion. To elucidate intracellular signals modified by CD34, we designed and constructed glutathione-S–transferase (GST)– fusion proteins of the intracellular domain of full-length CD34 (GST-CD34ifull). Precipitation of cell lysates using GST-CD34ifullidentified proteins of molecular mass 39, 36, and 33 kd that constitutively associated with CD34 and a 45-kd protein that associated with CD34 after adhesion. By Western analysis, we identified the 39-kd protein as CrkL. In vivo, CrkL was coimmunoprecipitated with CD34 using CD34 antibodies, confirming the association between CrkL and CD34. CD34 peptide inhibition assays demonstrated that CrkL interacts at a membrane-proximal region of the CD34 tail. To identify the CrkL domain responsible for interaction with CD34, we generated GST-fusion constructs of adapter proteins including GST-CrkL3′ (C-terminal SH3) and GST-CrkL5′ (N-terminal SH2SH3). Of these fusion proteins, only GST-CrkL3′ could precipitate endogenously expressed CD34, suggesting that CD34 binds the C-terminal SH3 domain of CrkL. Interestingly, there appears to be differential specificity between CrkL and CrkII for CD34, because GST-CD34ifull did not precipitate CrkII, a highly homologous Crk family member. Furthermore, GST-CD34ifull did not bind c-Abl, c-Cbl, C3G, or paxillin proteins that are known to associate with CrkL, suggesting that CD34 directly interacts with the CrkL protein. CD34ifull association with Grb or Shc adapter proteins was not detected. Our investigations shed new light on signaling pathways of CD34 by demonstrating that CD34 couples to the hematopoietic adapter protein CrkL.
Stimulation of autologous proliferative and cytotoxic T-cell responses by “leukemic dendritic cells” derived from blast cells in acute myeloid leukemia
Authors: Harrison Beth D. , Adams Julie A. , Briggs Mark , Brereton Michelle L. , Yin John A. Liu
Published: July 2002

Effective presentation of tumor antigens is fundamental to strategies aimed at enrolling the immune system in eradication of residual disease after conventional treatments. Myeloid malignancies provide a unique opportunity to derive dendritic cells (DCs), functioning antigen-presenting cells, from the malignant cells themselves. These may then co-express leukemic antigens together with appropriate secondary signals and be used to generate a specific, antileukemic immune response. In this study, blasts from 40 patients with acute myeloid leukemia (AML) were cultured with combinations of granulocyte-macrophage colony-stimulating factor, interleukin 4, and tumor necrosis factor α, and development to DCs was assessed. After culture, cells from 24 samples exhibited morphological and immunophenotypic features of DCs, including expression of major histocompatibility complex class II, CD1a, CD83, and CD86, and were potent stimulators in an allogeneic mixed lymphocyte reaction (MLR). Stimulation of autologous T-cell responses was assessed by the proliferative response of autologous T cells to the leukemic DCs and by demonstration of the induction of specific, autologous, antileukemic cytotoxicity. Of 17 samples, 11 were effective stimulators in the autologous MLR, and low, but consistent, autologous, antileukemic cytotoxicity was induced in 8 of 11 cases (mean, 27%; range, 17%-37%). This study indicates that cells with enhanced antigen-presenting ability can be generated from AML blasts, that these cells can effectively prime autologous cytotoxic T cells in vitro, and that they may be used as potential vaccines in the immunotherapy of AML.
EAF1, a novel ELL-associated factor that is delocalized by expression of the MLL-ELL fusion protein
Authors: Simone Federico , Polak Paul E. , Kaberlein Joseph J. , Luo Roger T. , Levitan Denise A. , Thirman Michael J.
Published: July 2002

The (11;19)(q23;p13.1) translocation in acute leukemia leads to the generation of a chimeric protein that fuses MLL to the transcriptional elongation factor ELL. A novel protein was isolated from a yeast 2-hybrid screen with ELL that was named EAF1 for ELL-associated factor 1. Using specific antibodies, the endogenous EAF1 and ELL proteins were coimmunoprecipitated from multiple cell lines. In addition, endogenous EAF1 also exhibited the capacity to interact with ELL2. Database comparisons with EAF1 identified a region with a high content of serine, aspartic acid, and glutamic acid residues that exhibited homology with the transcriptional activation domains of several translocation partner proteins of MLL, including AF4, LAF4, and AF5q31. A similar transcriptional activation domain has been identified in this region of EAF1. By confocal microscopy, endogenous EAF1 and ELL colocalized in a distinct nuclear speckled pattern. Transfection of theMLL-ELL fusion gene delocalized EAF1 from its nuclear speckled distribution to a diffuse nucleoplasmic pattern. In leukemic cell lines derived from mice transplanted withMLL-ELL–transduced bone marrow, EAF1 speckles were not detected. Taken together, these data suggest that expression of the MLL-ELL fusion protein may have a dominant effect on the normal protein-protein interactions of ELL.
Peripheral blood stem cell versus bone marrow allotransplantation: does the source of hematopoietic stem cells matter?
Authors: Körbling Martin , Anderlini Paolo
Published: July 2002

Hematopoietic stem cells from 4 different sources have been or are being used for the reconstitution of lymphohematopoietic function after myeloablative, near-myeloablative, or nonmyeloablative treatment. Bone marrow (BM)–derived stem cells, introduced by E. D. Thomas in 1963,1 are considered the classical stem cell source. Fetal liver stem cell transplantation has been performed on a limited number of patients with aplastic anemia or acute leukemia, but only transient engraftment has been demonstrated.2 Peripheral blood as a stem cell source was introduced in 1981,3 and cord blood was introduced as a source in 1988.4 The various stem cell sources differ in their reconstitutive and immunogenic characteristics, which are based on the proportion of early pluripotent and self-renewing stem cells to lineage-committed late progenitor cells and on the number and characteristics of accompanying “accessory cells” contained in stem cell allografts.
Blocking of c-FLIPL–independent cycloheximide-induced apoptosis or Fas-mediated apoptosis by the CC chemokine receptor 9/TECK interaction
Authors: Youn Byung-S. , Kim Young J. , Mantel Charlie , Yu Kang-Yeol , Broxmeyer Hal E.
Published: July 2002

Chemokines play a pivotal role in regulating leukocyte migration as well as other biological functions. CC chemokine receptor 9 (CCR9) is a specific receptor for thymus-expressed CC chemokine (TECK). It is shown here that engagement of CCR9 with TECK leads to phosphorylation of Akt (protein kinase B), mitogen-activated protein kinases (MAPKs), glycogen synthase kinase–3β (GSK-3β), and a forkhead transcription factor, FKHR, in a human T-cell line, MOLT4, that naturally expresses CCR9. By means of chemical inhibitors, it is shown that phosphoinositide-3 kinase (PI-3 kinase), but not MAPK, is required for CCR9-mediated chemotaxis. Akt, GSK-3β, FKHR, and MAPK have been previously implicated in cell survival signals in response to an array of death stimuli. When MOLT4 cells, which expressed Fas as well as CXCR4, were stimulated with cycloheximide (CHX), an agonistic anti-Fas antibody, or a combination of these, the cells rapidly underwent apoptosis. However, costimulation of MOLT4 cells with TECK or stromal derived factor–1 significantly blocked CHX-mediated apoptosis, whereas stimulation only with TECK partially blocked Fas-mediated apoptosis. Concomitant with this blocking, cleavage of poly (adenosine 5′-diphosphate–ribose) polymerase and activation of caspase 3 were significantly attenuated, but the expression level of FLICE inhibitory protein c-FLIPL, which had been shown to be regulated by CHX, was unchanged. This demonstrates that activation of CCR9 leads to phosphorylation of GSK-3β and FKHR and provides a cell survival signal to the receptor expressing cells against CHX. It also suggests the existence of a novel pathway leading to CHX-induced apoptosis independently of c-FLIPL.
Thrombopoietin therapy increases platelet yields in healthy platelet donors
Authors: Kuter David J. , Goodnough Lawrence T. , Romo John , DiPersio John , Peterson Randolph , Tomita Dianne , Sheridan William , McCullough Jeffrey
Published: July 2002

The recombinant thrombopoietins have been shown to be effective stimulators of platelet production in cancer patients. It was therefore of interest to determine if one of these, pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), could be used to increase platelet counts and consequently platelet yields from apheresis in healthy platelet donors. In a blinded, 2-cycle, crossover study, 59 platelet donors were randomized to receive a single subcutaneous injection of PEG-rHuMGDF (1 μg/kg or 3 μg/kg) or placebo and 15 days later undergo platelet apheresis. Donors treated with placebo had a median peak platelet count after PEG-rHuMGDF injection of 248 × 109/L compared with 366 × 109/L in donors treated with 1 μg/kg PEG-rHuMGDF and 602 × 109/L in donors treated with 3 μg/kg PEG-rHuMGDF. The median maximum percentage that platelet counts increased from baseline was 10% in donors who received placebo compared with 70% in donors who received 1 μg/kg and 167% in donors who received 3 μg/kg PEG-rHuMGDF. There was a direct relationship between the platelet yield and the preapheresis platelet count: Placebo-treated donors provided 3.8 × 1011 (range 1.3 × 1011-7.9 × 1011) platelets compared with 5.6 × 1011 (range 2.6 × 1011-12.5 × 1011) or 11.0 × 1011 (range 7.1 × 1011-18.3 × 1011) in donors treated with 1 μg/kg or 3 μg/kg PEG-rHuMGDF, respectively. Substandard collections (<3 × 1011 platelets) were obtained from 26%, 4%, and 0% of the placebo, 1 μg/kg, and 3 μg/kg donors, respectively. No serious adverse events were reported; nor were there events that met the criteria for dose-limiting toxicity. Thrombopoietin therapy can increase platelet counts in healthy donors to provide a median 3-fold more apheresis platelets compared with untreated donors.
Ataxia telangiectasia mutated–deficient B-cell chronic lymphocytic leukemia occurs in pregerminal center cells and results in defective damage response and unrepaired chromosome damage
Authors: Stankovic Tatjana , Stewart Grant S. , Fegan Christopher , Biggs Paul , Last James , Byrd Philip J. , Keenan Russell D. , Moss Paul A. H. , Taylor Alexander M. R.
Published: July 2002

B-cell chronic lymphocytic leukemia (B-CLL) is a heterogeneous disease involving more than one molecular mechanism that leads to the transformation of CD5+ B cells at either the pregerminal or postgerminal center stage of differentiation. It was previously demonstrated that ataxia telangiectasia mutated (ATM) gene mutations can occur in B-CLL and cause a defect in the p53 pathway. Here the role of ATM mutations in the pathogenesis of B-CLL is addressed. Of 50 B-CLL tumors with fully analyzedATM and TP53, 16 had ATM mutations. Six of 50 B-CLLs showed mutations in TP53 and the remaining 28 tumors had wild-type ATM or TP53. No tumor had both ATM and TP53 mutations. Remarkably, all 16 ATM mutant B-CLLs showed the absence of somatic variable region heavy chain hypermutation indicating a pregerminal center cell origin and a common pathogenesis for these tumors. Furthermore, in 5 of the 16 B-CLLs, ATMmutation preceded the transformation stage of differentiation. At the cellular level, ATM mutant tumors exhibited a deficient ATM-dependent p53 response to gamma irradiation, failure to up-regulate TRAIL-R2, a downstream target that links irradiation-induced p53 response with apoptosis, and an inability to repair induced chromosome breaks. Mantle cell lymphoma (MCL) is also of pregerminal center origin and ATMmutations are frequent in this malignancy. It is concluded that ATM is likely to play an important role at the pregerminal center stage and a model is proposed where loss of ATM function during B-cell ontogeny drives B-CLL tumorigenesis in pregerminal B cells by a dual defect in p53 damage response and repair of chromosome breaks.
Inhibition of macrophage inflammatory protein–1α production by Epstein-Barr virus
Authors: Jabs Wolfram J. , Wagner Hans J. , Maurmann Susanne , Hennig Holger , Kreft Burkhard
Published: July 2002

Infection with Epstein-Barr virus (EBV) exerts substantially immunomodulating activities in vitro and in vivo. In this context, EBV-induced chemokine production and the influence of EBV on this highly redundant system of inflammatory proteins have hardly been investigated. This study analyzed the production of interleukin-8, RANTES, monocyte chemotactic protein–1, and macrophage inflammatory protein–1α (MIP-1α) on EBV infection of peripheral blood mononuclear cells from immune EBV-seropositive (EBV+) and noninfected EBV-seronegative (EBV−) individuals. EBV failed to induce the production of MIP-1α in EBV+ as well as EBV− individuals, whereas the other chemokines studied were readily expressed. Moreover, EBV completely down-regulated lipopolysaccharide (LPS)– and phytohemagglutinin–induced MIP-1α production up to 4 hours after induction. Reverse transcription–polymerase chain reaction (RT-PCR) analysis of EBV- and LPS-stimulated cultures revealed that EBV inhibited MIP-1α production on the transcriptional level. This effect was abolished by addition of antiglycoprotein (gp)350/220, a monoclonal antibody against EBV's major envelope glycoprotein, which mediates binding of the virus to the EBV receptor, CD21. However, recombinant gp350/220 protein alone did not inhibit the LPS-induced MIP-1α production, indicating that infection of the target cell is indispensable for this effect. In summary, we demonstrate a new immunomodulating activity of EBV on the chemokine system that probably helps the virus to evade the host's immune system favoring lifelong infection.
High-Dose Chemotherapy in Poor-Prognosis Adult Small Round-Cell Tumors: Clinical and Molecular Results From a Prospective Study
Authors: Bertuzzi Alexia , Castagna Luca , Nozza Andrea , Quagliuolo Vittorio , Siracusano Licia , Balzarotti Monica , Compasso Silvana , Alloisio Marco , Soto Parra Hector , Santoro Armando
Published: July 2002

PURPOSE: The prognosis of metastatic/high-risk localized small round-cell tumors (SRCTs) treated conventionally is dismal. In this phase II study, we explored a high-dose chemotherapy (HD-CT) approach and analyzed the clinical significance of fusion transcripts detection.

PATIENTS AND METHODS: From June 1997 to November 1999, 28 SRCT patients (median age, 26 years; 14 peripheral primitive neuroectodermal tumors [pPNETs], seven rhabdomyosarcomas [RMSs], and seven desmoplastic small round-cell tumors [DSRCTs]) received induction chemotherapy with ifosfamide, epirubicin, and vincristine followed by HD-CT. Local treatment (radiotherapy and/or surgery) was performed when possible. Molecular analysis was performed on peripheral-blood and leukapheresis products by reverse-transcriptase polymerase chain reaction.

RESULTS: Overall response (OR) was 65% (18 of 28), with 40% complete response and 25% partial response. According to histology, the OR rate was 86% in pPNET and 43% in both RMS DSRCT. With a median follow-up of 35 months, median overall survival was 16 months and median progression-free survival (PFS) was 10 months. PFS was statistically better in pPNET than other histologic types (P = .0045). No correlation was found between the fusion transcript and clinical outcome during follow-up. Furthermore, transcript detection in leukapheretic products was not of prognostic significance.

CONCLUSION: Intensive HD-CT seems to enhance the response rate and survival when compared with conventional treatment in poor-prognosis pPNET. The poor results of this treatment in RMS and DSRCT do not support the inclusion of such an approach in these patient subsets. No definitive conclusions can currently be drawn concerning the clinical implications of the detection of fusion transcripts during treatment or follow-up.
Onasemnogene‐abeparvovec administration to premature infants with spinal muscular atrophy
Authors: Brown Stephen M. , Ajjarapu Aparna S. , Ramachandra Divya , Blasco‐Pérez Laura , Costa‐Roger Mar , Tizzano Eduardo F. , Sumner Charlotte J. , Mathews Katherine D.
Published: September 2024

Twin girls born at 30 weeks' gestation with spinal muscular atrophy (SMA) received onsasemnogene‐abeparvovec (OA) at 3.5 weeks of life. They had no treatment‐related adverse events, normal acquisition of motor milestones, and normal neurological examination at 19 months. Genotyping revealed 0 copies of SMN1 and a single, hybrid SMN2 gene containing the positive genetic modifier c.835‐44A>G. This was associated with full‐length SMN2 blood mRNA expression levels similar to a 2 copy SMA infant. The observed favorable outcomes are likely due to the genetic modifier combined with early drug administration enabled by prematurity.
Precise Clearance of Intracellular MRSA via Internally and Externally Mediated Bioorthogonal Activation of Micro/Nano Hydrogel Microspheres
Authors: Yang Jianye , Chen Li , Cai Zhengwei , Pang Libin , Huang Yanran , Xiao Pengcheng , Wang Juan , Huang Wei , Cui Wenguo , Hu Ning
Published: September 2024

Traditional high‐dose antibiotic treatments of intracellular methicillin‐resistant staphylococcus aureus (MRSA) are highly inefficient and associated with a high rate of infection relapse. As an effective antibacterial technology, sonodynamic therapy (SDT) may be able to break the dilemma. However, indiscriminate reactive oxygen species (ROS) release leads to potential side effects. This study incorporates Staphylococcal Protein A antibody‐modified Cu2+/tetracarboxyphenylporphyrin nanoparticles (Cu(II)NS‐SPA) into hydrogel microspheres (HAMA@Cu(II)NS‐SPA) to achieve precise eradication of intracellular bacteria. This eradication is under bioorthogonal activation mediated by bacillithiol (BSH) (internally) and ultrasound (US) (externally). To specify, the US responsiveness of Cu(II)NS‐SPA is restored when it is reduced to Cu(I)NS‐SPA by the BSH secreted characteristically by intracellular MRSA, thus forming a bioorthogonal activation with the external US, which confines ROS production within the infected MΦ. Under external US activation at 2 W cm−2, over 95% of intracellular MRSA can be cleared. In vivo, a single injection of HAMA@Cu(II)NS‐SPA achieves up to two weeks of antibacterial sonodynamic therapy, reducing pro‐inflammatory factor expression by 90%, and peri‐implant bone trabeculae numbers exceed the control group by five times. In summary, these micro/nano hydrogel microspheres mediated by internal and external bioorthogonal activation can precisely eliminate intracellular MRSA, effectively treating multi‐drug resistant intracellular bacterial infections.
An intersectional analysis of the health status, work conditions, and nonwork conditions of the U.S. working‐classed across class, sex, race, and nativity identities
Authors: Soh Eunice , Tsai Jenny Hsin‐Chun , Boutain Doris M. , Pike Kenneth
Published: September 2024

Background

Classism, sexism, racism, and nativism intersect to create inequitable conditions and health outcomes based on workers’ social identities. This study describes the health status, work conditions, and nonwork conditions of the United States (U.S.) working‐classed at the intersections of class, sex, racial, and nativity identities.

Methods

Descriptive statistics (e.g., frequencies, percentages) were calculated from the 2015 National Health Interview Survey data for the total working classed sample (N = 11,884) and 16 intersectional groupings. General and psychosocial health status, work factors, and access to resources outside of work were examined.

Results

Intersectional analysis revealed divisions in work and nonwork conditions despite the majority of each grouping reporting very good/excellent health. The majority of the female Latine born‐outside‐U.S. grouping (60%) reported not having paid sick leave. The majority of the male Latine born‐outside‐U.S. grouping reported having neither paid sick leave (62%) nor health insurance (55%). The majority of the female Latine (53%), male Latine (60%), and male Black (55%) born‐outside‐U.S. groupings reported workplaces as less safe. The majority of the female Latine born‐outside‐U.S. grouping (53%) was the only grouping to report being moderately/very worried about being able to afford housing costs.

Conclusion

The health status and precarity of work and nonwork conditions of the U.S. working classed may be shaped by intersecting systems of power across class, sex, racial, and nativity identities. Intersectional analysis increases our purview to see who is most affected, how, and where, which can inform future opportunities to mitigate worker health inequities.
Community music, identity and belonging among Dutchies in Australia: Comparing assimilation to multiculturalism
Authors: Dekker Karien , Broerse Jora , Peters Nonja
Published: September 2024

This article discusses variations in the experiences of Dutch identity and belonging to a music‐making group in the Dutch migrant community in Melbourne, Australia. It answers the research question “Which variations of ‘Dutch identity’ are there for the participants and how does music‐making relate to this?”. Feelings of identity and belonging are shaped by federal policies and micro‐interactions. This article builds on the concepts related to migrant identity and ethnomusicology in the context of two distinct federal integration policies: the White Australia policy (which is characterised by an assimilation policy) and multiculturalism. The findings showed that community music has the potential to bridge generational, gender and class differences. Multiculturalism, enabling the participants to meet and sing in Dutch, empowered them to explore their dual identity as Dutch Australians, intersecting with disability, racial differences, age and education level. This study improves our understanding of the impact of diverse emigration and immigration resettlement policies that form part of the complexities of diverse generations and backgrounds of the Dutch‐Australian diaspora.
A new iron recovery and dephosphorization approach from unroasted high‐phosphorus oolitic hematite ore via a facile chemical beneficiation process
Authors: Gong Minghui , Gao Likun , Dai Huixin , Tian Xiaosong , He Fei , Liu Mei , Rao Bing , Zhang Qingsong , Yin Zhaobo
Published: September 2024

Despite the abundance of scientific reports on the treatment of oolitic hematite, it still constitutes a global challenge. The distinctive oolitic structure within the ore is regarded as the primary factor causing the difficulty in the beneficiation of oolitic hematite ore. The objective of this study is to devise an effective approach to tackle the issue of beneficiation of oolitic hematite ore, thereby facilitating the utilization of oolitic hematite ore, which is widely abundant worldwide. Based on the Pourbaix diagram (Eh‐pH) of the Al‐Si‐H2O system, an alkaline leaching process for eliminating impurities from unroasted oolitic hematite using NaOH solution as the leaching agent was proposed. The optimal parameters were determined as a temperature of 250°C, a NaOH concentration of 16 mol/L, a liquid‐to‐solid ratio of 4 mL/g, and a reaction time of approximately 2 h. Around 54% of phosphorus (P), 21% of Al2O3, and 61% of SiO2 can be preliminarily removed from unroasted oolitic hematite ore. Through further dephosphorization with dilute sulfuric acid at room temperature, a high‐quality Fe concentrate with 63.3% Fe, 0.04% P, and a Fe recovery rate of 96% was obtained. The alkali can be readily regenerated by adding lime to the leaching solution, and the regenerated alkali has a leaching effect comparable to that of the fresh leaching solution. The recycling and utilization of alkaline leaching agents minimize production costs to the greatest extent possible. Mechanical studies have discovered that intact oolites undergo complete dissociation under alkaline leaching, enabling the leaching solution to permeate into the particles and thereby deeply eliminate impurities. The novel method has accomplished efficient processing of oolitic hematite and a reasonable control of production costs during processing, which is significant for expanding the reserves of iron ore resources.
Gender‐specific outcomes of low‐dose computed tomography screening for lung cancer detection: A retrospective study in Chinese never‐smoker population
Authors: Wang Huihong , Xie Jicheng , Chen Yahong , Jin Jiang , Zhang Meixian , Tung TaoHsin , Xu Youzu
Published: September 2024

Objectives

Low‐dose computed tomography (LDCT) has emerged as a pivotal tool for detecting lung cancer among ever‐smokers. This study aims to evaluate the gender‐specific outcomes of LDCT screening within the Chinese never‐smoking population.

Methods

We conducted a single‐center, retrospective cohort study, which analyzed LDCT screening outcomes for 42,018 asymptomatic participants. Specifically, we focused on assessing gender‐specific differences in the prevalence of pulmonary nodules, and the incidence of lung cancer diagnosis among never‐smokers.

Results

Among the 42,018 eligible participants, 41.50% were females and 58.50% were males. Most participants were non‐smokers (77.57%), with a significantly higher proportion of non‐smokers among females than males (99.33% vs. 62.14%). Pulmonary nodules were identified in 2.66% of participants, with a higher prevalence in females (2.99%) than males (2.43%) (p < 0.001). Non‐smoking females had a higher incidence of positive nodules than non‐smoking males (2.98% vs. 2.38%, p < 0.001). Invasive biopsies were performed in 334 individuals with nodules, confirming lung cancer in 258 cases. The majority of these cancer cases were non‐smokers (212), with non‐smoking females showing a higher incidence (0.85%) compared to males (0.43%) (p < 0.001). There was no significant difference in the false‐positive rates between non‐smoking females (0.14%) and males (0.13%). Multivariate analysis showed that never‐smoking women were more likely to undergo biopsies (OR 1.65, p = 0.0016) and had a higher, though not statistically significant, probability of lung cancer diagnosis (OR 1.84, p = 0.06).

Conclusion

This study elucidates sex‐based differences within the Chinese population, revealing a higher prevalence of pulmonary nodules and lung cancers among non‐smoking females. These findings offer valuable reference for both clinical practice and future research initiatives.
Anaerobic Digestion for Textile Waste Treatment and Valorization
Authors: Tharamrajah Naveenrajah , Shahbaz Kaveh , Baroutian Saeid
Published: September 2024

Textile waste is becoming among the most polluting waste in the world, discarded mostly in landfills. Valorizing textile waste via anaerobic digestion (AD) helps conserve resources, reduce environmental impact, and foster a circular economy. Although several reviews have discussed textile waste AD, there is a lack of detailed understanding of the challenges encountered during textile waste AD. Therefore, the goal of this review is to focus on challenges encountered and possible solutions for those challenges for biogas and fertilizer conversion via AD. Potential strategies include chemical, biological, and thermal pretreatments that significantly increase the digestion process. Co‐digestion of natural textile waste, cotton, and wool with carbon and nitrogen‐rich substrates improves AD efficiency by twofold. Moreover, separating polyester from polycotton and textile dye removal via solvent and advanced oxidation processes significantly increases methane yield compared with untreated textile waste. This review can aid in analyzing suitable methods to optimize the biogas production of textile waste via AD.
Validation of virtual fractional flow reserve pullback curves
Authors: Seki Ruiko , Collison Damien , Ikeda Kazumasa , Sonck Jeroen , Munhoz Daniel , Bertolone Dario Tino , Ko Brian , Maeng Michael , Otake Hiromasa , Koo Bon‐Kon , Storozhenko Tatyana , Bouisset Frederic , Belmonte Marta , Leone Attilio , Shumkova Monika , Ford Tom J. , Mahendiran Thabo , Berry Colin , De Bruyne Bernard , Oldroyd Keith , Sakai Koshiro , Mizukami Takuya , Collet Carlos
Published: September 2024

Background

Angiography‐derived fractional flow reserve (virtual FFR) has shown excellent diagnostic performance compared with wire‐based FFR. However, virtual FFR pullback curves have not been validated yet.

Objectives

To validate the accuracy of virtual FFR pullback curves compared to wire‐based FFR pullbacks and to assess their clinical utility using patient‐reported outcomes.

Methods

Pooled analysis of two prospective studies, including patients with hemodynamically significant (FFR ≤ 0.80) coronary artery disease (CAD). Virtual and wire‐based FFR pullbacks were compared to assess the accuracy of virtual pullbacks to characterize CAD as focal or diffuse. Pullbacks were analyzed visually and quantitatively using the pullback pressure gradient (PPG). Patients underwent PCI, and the Seattle Angina Questionnaire (SAQ) was administered at 3‐month follow‐up.

Results

A total of 298 patients (300 vessels) with both virtual and wire‐based pullbacks who underwent PCI were included in the analysis. The mean age was 61.8 ± 8.8, and 15% were female. The agreement on the visual adjudication of the CAD pattern was fair (Cohen's Kappa: 0.31, 95% confidence interval: 0.18–0.45). The mean PPG were 0.65 ± 0.18 from virtual pullbacks and 0.65 ± 0.13 from wire‐based pullbacks (r = 0.68, mean difference 0, limits of agreement −0.27 to 0.28). At follow‐up, patients with high virtual PPG (>0.67) had higher SAQ angina frequency scores (i.e., less angina) than those with low virtual PPG (SAQ scores 92.0 ± 14.3 vs. 85.5 ± 23.1, p = 0.022).

Conclusion

Virtual FFR pullback curves showed moderate agreement with wire‐based FFR pullbacks. Nonetheless, patients with focal disease based on virtual PPG reported greater improvement in angina after PCI.
Southwest Oncology Group S0826: A phase 2 trial of SCH 727965 (NSC 727135, dinaciclib) in patients with stage IV melanoma
Authors: Lao Christopher D. , Moon James , Ma Vincent T. , Fruehauf John P. , Flaherty Lawrence E. , Bury Martin J. , Martin William G. , Gross Howard , Akerley Wallace , Hopkins Judith O. , Patel Sapna P. , Sondak Vernon K. , Ribas Antoni
Published: September 2024

Background

Cell cycle inhibition is an established therapeutic approach for some cancers. A multicenter, single‐arm, phase 2 trial (ClinicalTrials.gov identifier NCT00937937) of the cyclin‐dependent kinase inhibitor SCH 727965 (NSC 747135; dinaciclib) was conducted in patients with metastatic melanoma to determine its clinical activity.

Methods

Patients with metastatic melanoma of cutaneous or mucosal origin were eligible if they had zero to one previous treatments, a Zubrod performance status of 0–1, and adequate organ function. SCH 727965 50 mg/m2 was given intravenously every 3 weeks until progression. Co‐primary end points were 1‐year overall survival (OS) and 6‐month progression‐free survival (PFS).

Results

Seventy‐two patients were enrolled from July 1, 2009, to November 1, 2010, at 24 institutions. Sixty‐eight percent of patients had M1c disease, and 43% had elevated lactate dehydrogenase levels. Twenty‐eight patients (39%) experienced grade 4 adverse events, including 20 cases of neutropenia. Sixty‐seven patients were evaluable for response. There was a response in zero of 67 patients (95% confidence interval [CI], 0%–5%), and stable disease was observed in 21%. The estimated median PFS was 1.4 months (95% CI, 1.4–1.5 months), and the 6‐month PFS rate was 6% (2%–13%). The median OS was 8.2 months (95% CI, 5.5–10.5 months), and the 1‐year OS rate was 38% (95% CI, 26%–49%).

Conclusions

This multicenter, US National Cancer Institute Cancer Therapy Evaluation Program‐sponsored trial of SCH 727965 was conducted at a time when the current generation of effective therapies for melanoma were not available. Although the null hypothesis of 1‐year OS was rejected, the minimal PFS impact and substantive toxicity indicated that this regimen lacks justification for further investigation as a single agent.