bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Ni–Al intermetallic sublayers on tribological properties of crystallised Ni–P coatings on aluminium substrates
Authors: Salehi M.
Published: June 2004

The effect of Ni–Al intermetallic sublayers on the tribological properties of Ni–P coated aluminium substrates has been investigated. For this purpose an Ni–P coating was directly deposited on to an 1100 aluminium substrate and Al–Ni diffusion sublayers were produced by subsequent vacuum heat treatment. The diffusion layers were characterised by optical and scanning electron microscopy (SEM), X-ray diffrac tion, microanalysis, and tribological testing. The results show that after annealing for 10 h at 520°C, three layers are formed with a total thickness of 3–4 times that of the initial Ni layer thickness. The layers grown during diffusion annealing are the intermediate phases of the Ni–Al system where their formation is controlled by process kinetics. The outermost layer was identified as a crystallised Ni–P residue along with two distinct layers of Ni2 Al3 and NiAl3 intermetallic compounds formed beneath it. The results of wear testing indicate much improved wear resistance after diffusion treatment, believed to result from a smooth hardness gradient and the formation of intermetallic phases at the interface, which acts as a firm sub strate beneath the hard crystallised Ni–P surface layer. From SEM studies of the wear debris and the worn specimens it can be concluded that delamination is the predominant wear mechanism of the surface layer.
Low temperature plasma carburising of austenitic stainless steels for improved wear and corrosion resistance
Authors: Sun Y. , Li X. , Bell T.
Published: June 2004

A novel plasma surface engineering process has been developed for engineering the surfaces of austenitic stainless steels to achieve combined improvements in wear and corrosion resistance. The process employs carbon as the major alloying species in the glow discharge of a plasma, facilitating the diffusion of carbon into the surfaces of various austenitic stainless steels and forming a precipitate free layer supersaturated with carbon at relatively low temperatures. This low temperature plasma surface alloying process produces a surface engineered layer several tens of micrometres thick, which has a high hardness together with excellent wear and corrosion resistance. The present paper describes various aspects of the novel process, concerning processing, structures, properties, and applications to engineering components.
Thrombopoietin responsiveness reflects the number of doublings undergone by megakaryocyte progenitors
Authors: Paulus Jean-Michel , Debili Najet , Larbret Frédéric , Levin Jack , Vainchenker William
Published: June 2004

To assess the variation of thrombopoietin (TPO) responsiveness associated with megakaryocyte (MK) progenitor amplification, TPO dose-response curves were obtained for normal human, single-cell plated CD34+CD41+ cells. The number of MKs per well was determined in situ and expressed as number of doublings (NbD). Dose-response curves of the mean frequency of clones of each size versus log TPO concentration showed highly significant differences in the TPO concentration needed for half-maximum generation of clones of different sizes (TPO50): 1.89 ± 0.51 pg/mL for 1 MK clones; 7.75 ± 0.81 pg/mL for 2 to 3 MK clones; 38.5 ± 5.04 pg/mL for 4 to 7 MK clones, and 91.8 ± 16.0 pg/mL for 8 to 15 MK clones. These results were consistent with a prediction of the generation-age model, because the number of previous doublings in vivo was inversely correlated with the number of residual doublings in vitro. TPO responsiveness decreased in vitro by a factor of 3.5 per doubling, reflecting the recruitment of progressively more ancestral progenitors. In support of this hypothesis, the more mature CD34+CD41+CD42+ cell fraction had a lower TPO50 (P < .001), underwent fewer NbD (P < .001), and expressed a 2.8-fold greater median Mpl receptor density (P < .001) than the CD34+CD41+CD42– fraction. Progenitors that have completed their proliferative program have maximum factor responsiveness and are preferentially induced to terminal differentiation.
An endothelial laminin isoform, laminin 8 (α4β1γ1), is secreted by blood neutrophils, promotes neutrophil migration and extravasation, and protects neutrophils from apoptosis
Authors: Wondimu Zenebech , Geberhiwot Tarekegn , Ingerpuu Sulev , Juronen Erkki , Xie Xun , Lindbom Lennart , Doi Masayuki , Kortesmaa Jarkko , Thyboll Jill , Tryggvason Karl , Fadeel Bengt , Patarroyo Manuel
Published: June 2004

During extravasation, neutrophils migrate through the perivascular basement membrane (BM), a specialized extracellular matrix rich in laminins. Laminins 8 (LN-8) (α4β1γ1) and 10 (LN-10) (α5β1γ1) are major components of the endothelial BM, but expression, recognition, and use of these laminin isoforms by neutrophils are poorly understood. In the present study, we provide evidence, using a panel of novel monoclonal antibodies against human laminin α4 (LNα4) chain, that neutrophils contain and secrete LN-8, and that this endogenous laminin contributes to chemoattractant-induced, αMβ2-integrin–dependent neutrophil migration through albumin-coated filters. Phorbol ester–stimulated neutrophils adhered to recombinant human (rh) LN-8, rhLN-10, and mouse LN-1 (mLN-1) (α1β1γ1) via αMβ2-integrin, and these laminin isoforms strongly promoted chemoattractant-induced neutrophil migration via the same integrin. However, only rhLN-8 enhanced the spontaneous migration. In addition, recruitment of neutrophils into the peritoneum following an inflammatory stimulus was impaired in LNα4-deficient mice. rhLN-8 also protected isolated neutrophils from spontaneous apoptosis. This study is the first to identify a specific laminin isoform in neutrophils and provides evidence for the role of LN-8 in the adhesion, migration, extravasation, and survival of these cells.
Identifying and characterizing a novel activating mutation of the FLT3 tyrosine kinase in AML
Authors: Jiang Jingrui , Paez J. Guillermo , Lee Jeffrey C. , Bo Ronghai , Stone Richard M. , DeAngelo Daniel J. , Galinsky Ilene , Wolpin Brian M. , Jonasova Anna , Herman Paula , Fox Edward A. , Boggon Titus J. , Eck Michael J. , Weisberg Ellen , Griffin James D. , Gilliland D. Gary , Meyerson Matthew , Sellers William R.
Published: June 2004

The FLT3 receptor is activated by juxtamembrane insertion mutations and by activation loop point mutations in patients with acute myeloid leukemia (AML). In a systematic tyrosine kinase gene exon resequencing study, 21 of 24 FLT3 exons were sequenced in samples from 53 patients with AML, 9 patients with acute lymphoblastic leukemia (ALL), and 3 patients with myelodysplasia samples. Three patients had novel point mutations at residue N841 that resulted in a change to isoleucine in 2 samples and to tyrosine in 1 sample. Introduction of FLT3-N841I cDNA into Ba/F3 cells led to interleukin-3 (IL-3)–independent proliferation, receptor phosphorylation, and constitutive activation of signal transducer and activator of transcription 5 (STAT5) and extracellular regulatory kinase (ERK), suggesting that the N841I mutation confers constitutive activity to the receptor. An FLT3 inhibitor (PKC412) inhibited the growth of Ba/F3-FLT3N841I cells (IC50 10 nM), but not of wild-type Ba/F3 cells cultured with IL-3. PKC412 also reduced tyrosine phosphorylation of the mutant receptor and inhibited STAT5 phosphorylation. Examination of the FLT3 autoinhibited structure showed that N841 is the key residue in a hydrogen-bonding network that likely stabilizes the activation loop. These results suggest that mutations at N841 represent a significant new activating mutation in patients with AML and that patients with such mutations may respond to small-molecule FLT3 inhibitors such as PKC412.
Inhibition of iron transport across human intestinal epithelial cells by hepcidin
Authors: Yamaji Sachie , Sharp Paul , Ramesh Bala , Srai Surjit Kaila
Published: June 2004

We investigated the effects of the iron regulatory peptide hepcidin on iron transport by the human intestinal epithelial Caco-2 cell line. Caco-2 cells were exposed to hepcidin for 24 hours prior to the measurement of both iron transport and transporter protein and mRNA expression. Incubation with hepcidin significantly decreased apical iron uptake by Caco-2 cells. This was accompanied by a decrease in both the protein and the mRNA expression of the iron-response element containing variant of the divalent metal transporter (DMT1[+IRE]). In contrast, iron efflux and iron-regulated gene1 (IREG1) expression were unaffected by hepcidin. Hepcidin interacts directly with a model intestinal epithelium. The primary effect of this regulatory peptide is to modulate the apical membrane uptake machinery, thereby controlling the amount of iron absorbed from the diet. (Blood. 2004;104:2178-2180)
Rescue of lethal c-KitW/W mice by erythropoietin
Authors: Waskow Claudia , Terszowski Grzegorz , Costa Céline , Gassmann Max , Rodewald Hans-Reimer
Published: June 2004

Homozygous natural white-spotted (W) mutations in the gene encoding the receptor tyrosine kinase c-Kit are associated with hypoplastic bone marrow, severe macrocytic anemia, and lethality during early postnatal life. c-KitW/W mice can be rescued by wild-type hematopoietic stem cells (HSCs), but it is not known whether the lethality of c-KitW/W mice is the result of HSC failure or defects specific for erythropoiesis. Here we show that transgenic expression of erythropoietin (EPO) can overcome the lethality caused by the c-KitW/W mutation. In W mutant mice rescued by EPO, termed WEPO, erythrocyte colony-forming units (CFU-Es) are rescued to normal frequencies. Hence, Epo receptor signals can partially bypass the strict requirement for c-Kit signaling in erythropoiesis in the absence of c-Kit in vivo. Using a series of W and rescue mouse strains, we define here the erythropoietic threshold permitting survival in vivo. The lethality of c-KitW/W mice has precluded analysis of this crucial receptor-ligand pair in adult stem/progenitor cells. Our strategy to generate viable c-KitW/W mice will be useful to analyze the role of this important receptor tyrosine kinase in adult life in vivo. (Blood. 2004; 104:1688-1695)
Immediate post-operative effects of tracheotomy on respiratory function during mechanical ventilation
Authors: Amygdalou Argyro , Dimopoulos George , Moukas Markos , Katsanos Christos , Katagi Athina , Mandragos Costas , Constantopoulos Stavros H , Behrakis Panagiotis K , Vassiliou Miltos P
Published: June 2004

Introduction

Tracheotomy is widely performed in the intensive care unit after long-term oral intubation. The present study investigates the immediate influence of tracheotomy on respiratory mechanics and blood gases during mechanical ventilation.

Methods

Tracheotomy was performed in 32 orally intubated patients for 10.5 ± 4.66 days (all results are means ± standard deviations). Airway pressure, flow and arterial blood gases were recorded immediately before tracheotomy and half an hour afterwards. Respiratory system elastance (Ers), resistance (Rrs) and end-expiratory pressure (EEP) were evaluated by multiple linear regression. Respiratory system reactance (Xrs), impedance (Zrs) and phase angle (φrs) were calculated from Ers and Rrs. Comparisons of the mechanical parameters, blood gases and pH were performed with the aid of the Wilcoxon signed-rank test (P = 0.05).

Results

Ers increased (7 ± 11.3%, P = 0.001), whereas Rrs (-16 ± 18.4%, P = 0.0003), Xrs (-6 ± 11.6%, P = 0.006) and φrs (-14.3 ± 16.8%, P = <0.001) decreased immediately after tracheotomy. EEP, Zrs, blood gases and pH did not change significantly.

Conclusion

Lower Rrs but also higher Ers were noted immediately after tracheotomy. The net effect is a non-significant change in the overall Rrs (impedance) and the effectiveness of respiratory function. The extra dose of anaesthetics (beyond that used for sedation at the beginning of the procedure) or a higher FiO2 (fraction of inspired oxygen) during tracheotomy or aspiration could be related to the immediate elastance increase.
cAMP protects neutrophils against TNF-α-induced apoptosis by activation of cAMP-dependent protein kinase, independently of exchange protein directly activated by cAMP (Epac)
Authors: Krakstad Camilla , Christensen Anne Elisabeth , Døskeland Stein Ove
Published: June 2004

It is unclear by which receptor cyclic adenosine monophosphate (cAMP) acts to promote neutrophil survival. We found that 8-(4-chlorophenylthio)-2′-O-methyl-cAMP, a specific activator of the recently discovered cAMP receptor, cAMP-regulated guanosine 5′-triphosphate exchange protein directly activated by cAMP, failed to protect human neutrophils from cell death. In contrast, specific activators of cAMP-dependent protein kinase type I (cA-PKI) could protect against death receptor [tumor necrosis factor receptor 1 (TNFR-1), Fas]-mediated apoptosis as well as cycloheximide-accelerated “spontaneous” apoptosis. A novel “caged” cA-PK-activating analog, 8-bromo (8-Br)-acetoxymethyl-cAMP, was more than 20-fold more potent than 8-Br-cAMP to protect neutrophils chalenged with TNF-α against apoptosis. This analog acted more rapidly than forskolin (which increases the endogenous cAMP production) and allowed us to demonstrate that cA-PK must be activated during the first 10 min after TNF-α challenge to protect against apoptosis. The protective effect was mediated solely through cA-PK activation, as it was abolished by the cA-PKI-directed inhibitor Rp-8-Br-cAMPS and the general cA-PK inhibitor H-89. Neutrophils not stimulated by cAMP-elevating agents showed increased apoptosis when exposed to the cA-PK inhibitors Rp-8-Br-cAMPS and H-89, suggesting that even moderate activation of cA-PK is sufficient to enhance neutrophil longevity and thereby contribute to neutrophil accumulation in chronic inflammation.
Unique phenotype of human uterine NK cells and their regulation by endogenous TGF-β
Authors: Eriksson Mikael , Meadows Sarah K , Wira Charles R , Sentman Charles L
Published: June 2004

Natural killer (NK) cells are a major population of lymphocytes in the human endometrium (EM), and NK cells can be a significant source of cytokines that alter local immune responses. The aim of this study was to determine the expression of NK cell receptors in situ and to test whether uterine NK (uNK) cells produce cytokines and how this activity may be regulated by transforming growth factor-β (TGF-β). We observed that human uNK cells were CD56+, CD3−, CD57−, CD9+, CD94+, killer inhibitory receptor+, and CD16+/− in situ by confocal microscopy. We examined cytokine production by uNK cells and uNK cell clones derived from human EM. Stimulation of uNK cells with interleukin (IL)-12 and IL-15, both of which are expressed in the human EM, induced interferon-γ (IFN-γ) and IL-10 production. IFN-γ production by uNK cell clones was completely inhibited by TGF-β1 in a dose-dependent manner with an inhibitory concentration 50% value of 20 pg/ml. IL-10 secretion by uNK cell clones was also inhibited by TGF-β1 at similar concentrations. Furthermore, blocking endogenous TGF-β in fresh human endometrial cell cultures increased the production of IFN-γ by uNK cells. These data indicate that uNK cells have a unique phenotype that is distinct from blood NK cells. Further, data demonstrate that uNK cells can produce immunoregulatory cytokines and that inhibition of uNK cells by locally produced TGF-β1 is a likely mechanism to regulate NK cell function in the human EM.
Loss of lineage antigens is a common feature of apoptotic lymphocytes
Authors: Diaz D , Prieto A , Barcenilla H , Monserrat J , Prieto P , Sánchez M A , Reyes E , Hernandez-Fuentes M P , de la Hera A , Orfao A , Alvarez-Mon M
Published: June 2004

The analysis of apoptosis in cell populations involves the detection of their specific lineage antigen (LAg) expression. This experimental approach relies on their assumed constant expression, but it is unclear whether such expression is actually maintained during cell death. We examined whether the loss of LAgs is a common feature of apoptotic lymphocytes and whether some might completely lose their LAgs. The changes in the expression of CD3, CD5, CD8, CD4, CD28, CD56, and CD19 were monitored in highly purified lymphocyte populations obtained by negative selection in a fluorescence-activated cell sorter. These were cultured for 24 h with or without phytohemagglutinin or staurosporin. For each LAg-positive subset studied, apoptosis was consistently more common among cells showing partial or total loss of LAg expression compared with cells maintaining their initial LAg levels. The kinetics of expression loss was rapid for CD8, CD56, and CD28, and more than 80% of initial expression was lost in the early stages of apoptosis but was slower for CD3, CD5, and CD4. For CD3 and CD5, expression was dependent on the apoptotic stimulus used. It is interesting that loss of antigen expression was independent of cell size. This phenomenon was also found in nonmanipulated, highly pure CD19 B lymphocytes of peripheral blood mononuclear cells from B chronic lymphocytic leukemia patients. Loss of LAg expression appeared to be a common feature of apoptotic lymphocytes under all the conditions assayed. The different kinetic patterns of LAg loss suggest apoptotic cells might actively regulate this process.
I-TAC/CXCL11 is a natural antagonist for CCR5
Authors: Petkovic Vibor , Moghini Christian , Paoletti Samantha , Uguccioni Mariagrazia , Gerber Basil
Published: June 2004

The selective CXC chemokine receptor 3 (CXCR3) agonists, monokine induced by interferon-γ (IFN- γ)/CXC chemokine ligand 9 (CXCL9), IFN-inducible protein 10/CXCL10, and IFN-inducible T cell α chemoattractant (I-TAC)/CXCL11, attract CXCR3+ cells such as CD45RO+ T lymphocytes, B cells, and natural killer cells. Further, all three chemokines are potent, natural antagonists for chemokine receptor 3 (CCR3) and feature defensin-like, antimirobial activities. In this study, we show that I-TAC, in addition to these effects, acts as an antagonist for CCR5. I-TAC inhibited the binding of macrophage-inflammatory protein-1α (MIP-1α)/CC chemokine ligand 3 (CCL3) to cells transfected with CCR5 and to monocytes. Furthermore, cell migration evoked by regulated on activation, normal T expressed and secreted (RANTES)/CCL5 and MIP-1β/CCL4, the selective agonist of CCR5, was inhibited in transfected cells and monocytes, respectively. In two other functional assays, namely the release of free intracellular calcium and actin polymerization, I-TAC reduced CCR5 activities to minimal levels. Sequence and structure analyses indicate a potential role for K17, K49, and Q51 of I-TAC in CCR5 binding. Our results expand on the potential role of I-TAC as a negative modulator in leukocyte migration and activation, as I-TAC would specifically counteract the responses mediated by many “classical,” inflammatory chemokines that act not only via CCR3 but via CCR5 as well.
Holocene palaeoecology and climate history of South Georgia (sub-Antarctica) based on a macrofossil record of bryophytes and seeds
Authors: Van der Putten Nathalie , Stieperaere Herman , Verbruggen Cyriel , Ochyra Ryszard
Published: June 2004

The results are presented of a detailed plant macrofossil analysis of a(14C dated Holocene organic sequence from a sub-Antarctic island, South Georgia. In the peat infilling of a rock basin 31 bryophyte species and many of the principal species of the present-day angiosperm flora, associated with bog communities, have been identified. The zonation of the bryophytes and the seeds and fruits shows a striking correspondence with the sediment stratigraphy, and indicates five ecological phases. The first four reflect a succession from a minerotrophic shallow pool to an ombrotrophic W arnstorfia-Polytrichum bog. After the deposition of a greyish-brown layer, c. 2200 14C years BP, a wet Deschampsia-Warnstorfia-Sanionia-Rostkovia bog came into existence, which is still present today. The ecological phases are radiocarbon dated. They can be interpreted in terms of climate development during the Holocene. Climate ameliorated rapidly at about 10 000 14C years BP followed by a drier period. Around 7000 14C years BP the climate became wetter and the following c. 2500years probably represent the climatic optimum. Between 4500 and 2600 14C years BP, drier conditions prevailed at the study site. The most striking change occurred at 2600 14C years BP when a marked change in vegetation and ecology indicates much wetter conditions.
High-resolution petrophysical and palaeomagnetic study of late-Holocene shelf sediments, Salerno Gulf, Tyrrhenian Sea
Authors: Iorio M. , Sagnotti L. , Angelino A. , Budillon F. , D'Argenio B. , Dinarès-Turell J. , Macrì P. , Marsella E.
Published: June 2004

Records of geomagnetic secular variation have been obtained from three cores recovered from the Salerno Gulf (southern Italy). High-resolution petrophysical and palaeomagnetic measurements enabled the reconstruction of a composite curve of geomagnetic palaeosecular variation (PSV), which is compared with the reconstructed PSV curve from Britain and with the French archaeomagnetic data of the last 2.1ka. The good agreement of the Salerno Gulf record with the above data conforms that our PSV record reaches back for some 9.0ka. In addition to a thick pumice layer originated during the Somma-Vesuvius eruption at 79, two other tephra layers were recognized, at about 1.3 and 3.0ka BP, that are probably also of Vesuvian origin. The comparison provides an initial chronological framework for assessing the increasing trend of sedimentation rate and its significant changes at about 2.7ka and 7.0ka BP. This variation in the deposition rate suggests a link with climatic changes recognized in the Mediterranean region.
American Society of Clinical Oncology Recommendations for the Initial Hormonal Management of Androgen-Sensitive Metastatic, Recurrent, or Progressive Prostate Cancer
Authors: Loblaw D. Andrew , Mendelson David S. , Talcott James A. , Virgo Katherine S. , Somerfield Mark R. , Ben-Josef Edgar , Middleton Richard , Porterfield Henry , Sharp Stewart A. , Smith Thomas J. , Taplin Mary Ellen , Vogelzang Nicholas J. , Wade James L. , Bennett Charles L. , Scher Howard I.
Published: June 2004

Purpose

To develop a clinical practice guideline for the management of men with metastatic, recurrent, or progressive carcinoma of the prostate. The focus of this document is on the use, combinations, and timing of various forms of androgen deprivation therapy (ADT) for the palliation of men with androgen-sensitive disease.

Methods

An expert panel and writing committee were formed. The questions to be addressed by the guideline were determined, and a systematic review of the literature was performed, which included a search of online databases, bibliographic review, and consultation with content experts. A priori criteria were used to select studies for analysis and study authors were contacted when necessary.

Results

There were 10 randomized controlled trials, six systematic reviews, and one Markov model available to inform the guidelines.

Conclusion

A full discussion between practitioner and patient should occur to determine which therapy is best for the patient. Bilateral orchiectomy or luteinizing hormone releasing hormone agonists are the recommended initial treatments. Nonsteroidal antiandrogen therapy may be discussed as an alternative, but steroidal antiandrogens should not be offered as monotherapy. Patients willing to accept the increased toxicity of combined androgen blockage for a small benefit in survival should be offered nonsteroidal antiandrogen in addition to castrate therapy. Until data from studies using modern medical diagnostic/biochemical tests and standardized follow-up schedules become available, no specific recommendations can be issued regarding the question of early versus deferred ADT. A discussion about the pros and cons of early versus deferred ADT should occur.
Pyruvate Prevents Restraint-Induced Immunosuppression via Alterations in Glucocorticoid Responses
Authors: Neigh Gretchen N. , Bowers Stephanie L. , Pyter Leah M. , Gatien Michelle L. , Nelson Randy J.
Published: June 2004

Stress-evoked immunosuppression may reflect increased demands on cellular energy signaled via elevated glucocorticoid concentrations. We hypothesized that treatment with pyruvate, an alternative energy source, would ameliorate restraint-induced elevation of glucocorticoids and that this reduction in glucocorticoid exposure will prevent stress-induced immunosuppression. We provided exogenous pyruvate to mice exposed to repeated restraint and then assessed splenocyte counts and splenocyte proliferation in response to the mitogen, concanavalin A as well as IgM production in response to keyhole limpet hemocyanin. Immune function was suppressed in mice undergoing repeated restraint but not in mice exposed to repeated restraint followed by pyruvate treatment. All mice exposed to restraint, regardless of pyruvate supplementation, displayed equivalent occurrences of repeated elevations in corticosterone concentrations; however, the cumulative exposure to corticosterone after one episode of restraint was reduced in those mice treated with pyruvate after restraint. Finally, we tested the immunoprotective ability of pyruvate supplementation in the presence of chronically elevated corticosterone. Mice implanted with restraint-like concentrations of corticosterone after adrenalectomy decreased splenocyte counts, compared with either unmanipulated mice or mice that were implanted with a cholesterol pellet after adrenalectomy, regardless of pyruvate supplementation. These data suggest that pyruvate does not possess immunoprotective properties in the presence of chronically elevated corticosterone. Pyruvate supplementation preserves immune function during exposure to repeated restraint stressors; altered dynamics of corticosterone concentrations after pyruvate administration may mediate this immunoprotection. Pyruvate prevents restraint-induced immunosuppression via alterations in the glucocorticoid response to restraint.
Engrailed genes are cell-autonomously required to prevent apoptosis in mesencephalic dopaminergic neurons
Authors: Albéri Lavinia , Sgadò Paola , Simon Horst H.
Published: June 2004

The neuropathological hallmark of Parkinson’s disease is the loss of dopaminergic neurons in the substantia nigra pars compacta, presumably mediated by apoptosis. The homeobox transcription factors engrailed 1 and engrailed 2 are expressed by this neuronal population from early in development to adulthood. Despite a large mid-hindbrain deletion in double mutants null for both genes, mesencephalic dopaminergic (mDA) neurons are induced, become postmitotic and acquire their neurotransmitter phenotype. However, at birth, no mDA neurons are left. We show that the entire population of these neurons is lost by E14 in the mutant animals, earlier than in any other described genetic model system for Parkinson’s disease. This disappearance is caused by apoptosis revealed by the presence of activated caspase 3 in the dying tyrosine hydroxylase-positive mutant cells. Furthermore, using in vitro cell mixing experiments and RNA interference on primary cell culture of ventral midbrain we were able to show that the demise of mDA neurons in the mutant mice is due to a cell-autonomously requirement of the engrailed genes and not a result of the missing mid-hindbrain tissue. Gene silencing in the postmitotic neurons by RNA interference activates caspase 3 and induces apoptosis in less than 24 hours. This rapid induction of cell death in mDA neurons suggests that the engrailed genes participate directly in the regulation of apoptosis, a proposed mechanism for Parkinson’s disease.
Baculovirus P35 inhibits NO-induced apoptosis in activated macrophages by inhibiting cytochrome c release
Authors: Ranjan Priya , Shrivastava Punya , Singh Sukh Mahendra , Sodhi Ajit , Heintz Nicholas H.
Published: June 2004

The baculovirus protein P35 inhibits apoptosis in a diverse range of animals such as insects, nematodes and mammals. Evidence suggests that P35 can inhibit members of caspase family proteases that are key mediators of mammalian apoptosis. We demonstrate that p35 inhibits activation-induced nitric oxide (NO)-mediated apoptosis in the RAW 264.7 mouse macrophages. Parent or vector-transfected RAW 264.7 cells underwent apoptosis when treated with a combination of cisplatin and interferon-γ (IFN-γ) or LPS and IFN-γ in a NO-dependent manner. By contrast, RAW 264.7 cells stably expressing P35 did not undergo apoptosis when treated with a combination of cisplatin and IFN-γ or LPS and IFN-γ. Activation of parent, vector- or p35-transfected cells with cisplatin and IFN-γ or LPS and IFN-γ caused equivalent levels of inducible nitric oxide synthase (iNOS) expression and produced equal amounts of nitrite, which ruled out attenuated iNOS activity during P35-mediated protection. Rather, expression of P35 inhibited translocation of mitochondrial cytochrome c into cytosol, mitochondrial depolarization, activation of caspase-9 and caspase-3, and cleavage of poly (ADP-ribose) polymerase (PARP). These findings indicate that P35 inhibits NO-induced apoptotic cell death of activated macrophages by inhibiting mitochondrial cytochrome c release, which suggests that P35 has targets upstream of the caspase cascade in apoptosis.
Akt binds prohibitin 2 and relieves its repression of MyoD and muscle differentiation
Authors: Sun Luguo , Liu Lanying , Yang Xiang-Jiao , Wu Zhenguo
Published: June 2004

In a yeast two-hybrid screen using the full-length Akt as bait, we found that prohibitin 2 (PHB2) specifically interacts with Akt. The C terminus of Akt (amino acids 413-480) and a central region of PHB2 (amino acids 120-232) are responsible for their mutual interaction. PHB2 acts as a transcriptional repressor in cells. PHB2 interacts with both MyoD and MEF2, and represses both MyoD- and MEF2-dependent gene transcription. Furthermore, binding of PHB2 to both MyoD and MEF2 significantly decreases upon myogenic differentiation. When stably expressed in C2C12 myogenic cells, PHB2 inhibits myogenin induction and phenotypic muscle differentiation. PHB2 was found to specifically recruit histone deacetylase 1, which is probably responsible for its repressive activity. Co-expression of Akt can partially reduce PHB2 binding to MyoD and relieve the repressive effect of PHB2 on myogenic reporters, which could be one of the mechanisms underlying Akt-mediated MyoD activation and accelerated muscle differentiation.
The soluble D2D388-274 fragment of the urokinase receptor inhibits monocyte chemotaxis and integrin-dependent cell adhesion
Authors: Furlan Federico , Orlando Simone , Laudanna Carlo , Resnati Massimo , Basso Veronica , Blasi Francesco , Mondino Anna
Published: June 2004

We have previously shown that chymotrypsin-cleaved soluble uPAR (D2D388-274) elicits migration of monocytic cells through interaction with FPRL-1, a G protein-coupled receptor that is homologous to the fMLP receptor. Here, we report that D2D388-274 also modulates the ability of monocytes to migrate in response to other chemokines. Pretreatment of monocytes with increasing amounts of D2D388-274 prevents cell migration in response to MCP-1, RANTES and fMLP. We demonstrate that D2D388-274 does not inhibit MCP-1 receptor binding, elicit CCR2 internalization and prevent MCP-1-induced intracellular Ca2+ increase. Thus, CCR2 receptor desensitization cannot account for D2D388-274-mediated inhibition of MCP-1-induced cell migration. Rather, we show that pretreatment of monocytes with D2D388-274 dramatically decreases chemokine-induced integrin-dependent rapid cell adhesion by interacting with FPRL-1. Together, our results indicate that chemokine-dependent cell migration can be regulated not only by homologous and heterologous receptor desensitization, but also by inhibition of integrin-dependent cell adhesion, an important step in cell transmigration.
A role for yeast oxysterol-binding protein homologs in endocytosis and in the maintenance of intracellular sterol-lipid distribution
Authors: Beh Christopher T. , Rine Jasper
Published: June 2004

The seven yeast OSH genes (OSH1-OSH7) encode a family of orthologs of the mammalian oxysterol-binding protein (OSBP). The OSH genes share at least one essential overlapping function, potentially linked to the regulation of secretory trafficking and membrane lipid composition. To investigate the essential roles of the OSH genes, we constructed conditional OSH mutants and analyzed their cellular defects. Elimination of all OSH function altered intracellular sterol-lipid distribution, caused vacuolar fragmentation, and resulted in an accumulation of lipid droplets in the cytoplasm and within vacuolar fragments. Gradual depletion of Osh proteins also caused cell budding defects and abnormal cell wall deposition. In OSH mutant cells endocytosis was severely impaired, but protein transport to the vacuole and the plasma membrane was largely unaffected. Other mutants affecting sterol-lipid function and distribution, namely erg2Δ and arv1Δ, shared similar defects. These findings suggested that OSH genes, through effects on intracellular sterol distribution, establish a plasma membrane lipid composition that promotes endocytosis.
Brittle-ductile transition in monocrystalline silicon analysed by molecular dynamics simulation
Authors: Tanaka H , Shimada S , Ikawa N
Published: June 2004

For a better understanding of essential mechanisms of material removal at extremely small depth of cut and of the brittle-ductile transition in the material removal process of monocrystalline silicon, nonometric deformation behaviour in three-point bending of defect-free monocrystalline silicon is analysed by molecular dynamics (MD) computer simulation. MD simulations show that plastic deformation takes place through a phase transformation from diamond to amorphous structures. The critical octahedral shearing stress for phase transformation is estimated to be 12–14 GPa. In the deformed region, a crack nucleus on atomic scale can be generated owing to thermally activated vibration of atoms. After the crack nucleus, the crack extension takes place under a certain stress field. The crack initition takes place when a tensile stress reaches a certain critical value of about 30 GPa at the crack nucleus. The critical values for plastic deformation and crack initiation depend on crystal orientation and hydrostatic pressure. It is shown that there can also be critical criteria of the stress field to determine whether plastic deformation or crack initiation would predomiantly take place. When the plastic deformation proceeds to a crack initiation, ductile mode machining can be realized.
Response of copper nanowires in dynamic tensile deformation
Authors: Liang W , Zhou M
Published: June 2004

Molecular dynamics (MD) simulations with an embedded atom method (EAM) potential are carried out to analyse the size and strain rate effects in the tensile deformation of single-crystal copper nanowires. The cross-sections of the wires are squares with dimensions of between 5 and 20 lattice constants (or 1.8-7.2nm). Deformations under constant strain rates between 1.67 × 107 and 1.67 × 1010s−1 are analysed. It is found that the yield stress decreases with specimen size and increases with loading rate. On the other hand, ductility increases with specimen size and strain rate. The influence of specimen size is due to enhanced opportunities for dislocation motion at larger sizes. The influence of strain rate is due to the dynamic wave effect or phonon drag which impedes the motion of dislocations. The analysis also focuses on the variation in deformation mechanisms with specimen size and strain rate. Slip along alternating (111) planes is observed in small wires, while multiple cross-slips are primarily responsible for the progression of plastic deformation in larger wires. As strain rate is increased, a transition of the deformation mechanism from sequential propagation of slip along well-defined and favourably oriented slip planes to cross-slip, and then to amorphization, is observed.
The influence of non-dissipative quantities in kinematic hardening plasticity
Authors: Wallin M , Ristinmaa M , Ottosen N S
Published: June 2004

A kinematic hardening plasticity model valid for finite strains is presented. The model is based on the well-known multiplicative split of the deformation gradient into elastic and plastic parts. The basic ingredient in the formulation is the introduction of a locally defined configuration—a centre configuration—which is associated with a deformation gradient that is used to characterize the kinematic hardening behaviour. The non-dissipative quantities allowed in the model are found when the plastic and kinematic hardening evolution laws are split into two parts: a dissipative part, which is restricted by the dissipation inequality, and a non-dissipative part, which can be chosen without any thermodynamic considerations. To investigate the predictive capabilities of the proposed kinematic hardening formulation, necking of a bar is considered. Moreover, to show the influence of the non-dissipative quantities, the simple shear problem and torsion of a thin-walled cylinder are considered. The numerical examples reveal that the non-dissipative quantities can affect the response to a large extent and are consequently valuable and important ingredients in the formulation when representing real material behaviour.
Multipass low-plasticity burnishing induced residual stresses: Three-dimensional elastic-plastic finite element modelling
Authors: Zhuang W , Wicks B
Published: June 2004

Low-plasticity burnishing (LPB) is a surface modification process involving complex cyclic plastic deformation that results in the development of a deep residual stress field. In order to achieve an optimal LPB-induced residual stress field for the geometry appropriate to the aircraft engine component, the key parameters of the LPB process, such as burnishing load, burnishing ball size and material properties, need to be determined. For this purpose, a three-dimensional non-linear moving contact finite element model is proposed to simulate the multipass LPB process and to predict the effects of those parameters on the resultant residual stress field. The material constitutive model used in the finite element analysis has been developed from the cyclic stress/strain response obtained from experimental measurements on the material. Prediction of the LPB-induced residual stresses by the finite element model appears to agree reasonably well with X-ray diffraction measurements.
A flexible digit with tactile feedback for invasive clinical applications
Authors: Ma X , Brett P N , Wright M T , Griffiths M V
Published: June 2004

This paper describes research on measurement of tactile sense using a flexible digit appropriate to endoscopy and minimal access surgery. It is envisaged that the sensing method will facilitate the navigation of flexible invasive devices, such as endoscopes, and also aid diagnosis using tactile perception as well as visual observation. The proposed master-slave digit system incorporates the application of the distributive sensing method applied to tactile sensing in order to discriminate different contact conditions of the flexible digit. The paper concentrates on the description of the application of this method and places this in the context of the user and the integrated system. The approach to sensing is able to discriminate the position, magnitude, distributed profile and width of the applied contacting load by using only four sensing points. Values to describe these parameters are evaluated to an accuracy greater than 93 per cent.
Relationship Between MMR Vaccine and Autism
Authors: Klein Kristin C , Diehl Emily B
Published: June 2004

OBJECTIVE:

To evaluate the proposed link between the administration of the measles, mumps, and rubella (MMR) vaccine and the development of autism.

DATA SOURCES:

A literature search utilizing MEDLINE (1966–November 2003), with the key terms measles, mumps, rubella, and autism, was conducted. Review of the references listed in the articles identified was also performed.

DATA SYNTHESIS:

Ten articles that specifically evaluated the possible relationship between the MMR vaccine and autism were identified. Review articles, commentaries, and evaluations of a link between gastrointestinal symptoms in autistic children and MMR immunization were excluded.

CONCLUSIONS:

Based upon the current literature, it appears that there is no relationship between MMR vaccination and the development of autism.
Unintentional Intravenous Infusion of Golytely in a 4-Year-Old Girl
Authors: Rivera Wilfredo , Velez Larissa I , Guzman Daniel D , Shepherd Greene
Published: June 2004

OBJECTIVE:

To report an accidental intravenous infusion of Golytely (polyethylene glycol and electrolyte solution; PEG-ELS) in a pediatric patient that did not result in systemic toxicity.

CASE SUMMARY:

A 4-year-old Hispanic girl presented to the emergency department after ingestion of approximately 24 tablets of 6-mercaptopurine (6-MP) 2 hours earlier. She vomited twice after receiving syrup of ipecac at home. Upon arrival, her vital signs were temperature 36.2 °C, heart rate 102 beats/min, respiratory rate 42 breaths/min, and blood pressure 115/67 mm Hg. Her physical examination was normal. The patient received activated charcoal 1 g/kg. Golytely administered through a nasogastric tube was ordered. Upon reevaluation, it was noted that the patient had received 391 mL of Golytely intravenously. The infusion was immediately stopped. There was no evidence of acidosis, renal failure, or ethylene glycol toxicity. She was admitted for observation and was discharged 36 hours later.

DISCUSSION:

As of April 29, 2004, accidental intravenous infusion of PEG-ELS has not been previously reported. Potential toxicity from Golytely is mainly related to the molecular weight of PEG in the formulation. PEG can theoretically be degraded to ethylene glycol. It is thus important to monitor acid—base status, renal function, and pulmonary function in these patients.

CONCLUSIONS:

When administered correctly, an infusion of PEG-ELS by nasogastric tube is a safe gastrointestinal decontamination technique used in toxicology; PEG-ELS is not indicated for intravenous administration. Protocols need to be implemented in the workplace to minimize errors in the delivery of treatment to patients. Fortunately, this patient did not have any toxicity from the intravenous infusion of Golytely.
Employee stock ownership plans and three‐component commitment
Authors: Culpepper Robert A. , Gamble John E. , Blubaugh Meg G.
Published: June 2004

Previous studies of employee ownership have conceptualized its chief attitudinal outcome principally as an emotional bond to the organization (i.e. affective commitment), despite a growing consensus that commitment is multifaceted. Using a sample of airline pilots, we assessed relationships between ESOP (employee stock ownership plan) attributes and three‐component commitment (Meyer & Allen, 1991). Regarding continuance commitment, high financial value was associated with pilots feeling freer to leave rather than being bound to the organization, as side‐bet theory suggests. As predicted, perceived workplace empowerment was strongly related to normative commitment — consistent with Meyer and Allen's theoretical formulation emphasizing unfulfilled reciprocity norms but inconsistent with the non‐contingent, loyalty norm explanation.
Working in a violent environment: The accuracy of police officers' reports about shooting incidents
Authors: Beehr Terry A. , Ivanitskaya Lana , Glaser Katherine , Erofeev Dmitry , Canali Kris
Published: June 2004

The occupational stress of chronic working conditions in police organizations has been examined in the past, but the effects of acute stressful events are much more difficult to study systematically. Experienced police officers' memories for elements of a simulated stressful crime scene involving an on‐duty shooting incident were examined. Officers were exposed to one of three situations varying in stress. In a 3 × 2 factorial design, some officers reviewed their memories by answering questions immediately after the shooting, while others did not. Twelve weeks later, officers' long‐term memories were better for all elements of the crime scene if they had rehearsed. Under some conditions, officers tended to remember the most important elements better (i.e. the number of armed people present) and the least important elements worse (i.e. irrelevant objects). In addition, their confidence in their memories had little or no relationship to their memories' accuracy and there was a threat focus in which objects physically closest to the points of threat were remembered better. There are strong implications for two elements of job performance: writing police reports and testifying in court.
The importance of ethnic similarity in the therapist‐patient dyad among Surinamese migrants in Dutch mental health care
Authors: Knipscheer Jeroen W. , Kleber Rolf J.
Published: June 2004

Empirical evidence is equivocal on whether ethnic matching in the therapist‐patient dyad is preferred by ethnic minority patients and whether it leads to treatment satisfaction. The aim of this study was to establish the importance of ethnic similarity in mental health care among Surinamese migrants in the Netherlands. A convenience sample of Surinamese out‐patients in community mental health care (N = 96) was interviewed. Data were analysed using logistic multivariate techniques. The majority of the Surinamese out‐patients (in particular recently residing participants) rated ethnic matching as relevant; a considerable minority considered compassion and expertise to be more relevant than ethnic background. Most out‐patients reported to be satisfied with the services, especially females and respondents treated by an ethnically similar therapist. Ethnic similarity in the patient‐therapist dyad is a strong predictor for satisfaction with mental health care services. However, although it is preferred by many, ethnic matching per se is no must ‐ empathy, expertise and world view sharing are reported to be of considerable importance as well.
Police Officers' Perceptions of Maps and Aerial Photographs
Authors: Canter Philip , Harries Keith
Published: June 2004

With the increasing adoption of geographic information systems (GIS) by police departments and other law enforcement agencies around the world, the issue of how effectively maps and related media communicate information has become germane. In the police department, Baltimore County, Maryland, USA, a small sample survey of police officers was conducted in order to test the utility of alternative visualisations of crime data presented at varying geographic scales. The ultimate objective was to enhance understanding of the effectiveness of maps and aerial photographs commonly used in the context of various investigative, community, managerial, and other applications of GIS tools. Generally, representations containing richer detail were preferred over the conventional abstract linear maps that are usually the default in the context of GIS. Given this situation, faster microprocessors and cheap mass storage provide a rationale for making available maps and other imagery providing police department personnel with intensely rich visualisations of their environments. The underlying assumption is that richer images convey more information and ultimately result in better decision-making.

This research was supported by a grant from the US Department of Justice, National Institute of Justice. Points of view are those of the authors and do not necessarily represent the official position of the US Department of Justice. The authors contributed equally to the research.