bluuebunny/crossref_metadata_2025 huggingface dataset:
THE CONTRIBUTION OF THE LIGHT QUARK CONDENSATE TO THE πN SIGMA TERM
Authors: GIBBS W. R.
Published: June 2005

There has been a discrepancy between values of the pion-nucleon sigma term extracted by two different methods for many years. Analysis of recent high precision pion-nucleon data has widened the gap between the two determinations. It is argued that the two extractions correspond to different quantities and that the difference between them can be understood and calculated.
S, P, D, F WAVE KN PHASE SHIFTS IN THE CHIRAL SU(3) QUARK MODEL
Authors: HUANG F. , ZHANG Z. Y. , YU Y. W.
Published: June 2005

The S, P, D, F wave KN phase shifts have been studied in the chiral SU (3) quark model by solving a resonating group method equation. The numerical results of different partial waves are in agreement with the experimental data except for the cases of P13 and D15, which are less well described when the laboratory momentum of the kaon meson is greater than 400 MeV.
KLOE RESULTS AT THE FRASCATI ϕ-FACTORY DAΦNE
Authors:   Presented for the KLOE Collaboration: A. Aloisio, F. Ambrosino, A. Antonelli, M. Antonelli, C. Bacci, M. Barva, G. Bencivenni, S. Bertolucci, C. Bini, C. Bloise, V. Bocci, F. Bossi, P. Branchini, S. A. Bulychjov, R. Caloi, P. Campana, G. Capon, T. Capussela, G. Carboni, F. Ceradini, F. Cervelli, F. Cevenini, G. Chiefari, P. Ciambrone, S. Conetti, E. De Lucia, A. De Santis, P. De Simone, G. De Zorzi, S. Dell'Agnello, A. Denig, A. Di Domenico, C. Di Donato, S. Di Falco, B. Di Micco, A. Doria, M. Dreucci, O., MÜLLER STEFAN E.
Published: June 2005

The KLOE experiment at the Frascati ϕ-factory DAΦNE has collected about 0.5 fb-1 of data till the end of the year 2002. These data allow to perform a wide physics program, ranging from the physics of charged and neutral kaons to radiative ϕ-decays. Results are presented for the KL lifetime and the semileptonic processes KS,L→πeν. From the light meson spectroscopy program, results on the decays ϕ→f0(980)γ, a0(980)γ as well as ϕ→ηγ, η′γ are presented.
HEAVY QUARKONIUM π+π- TRANSITIONS AND A POSSIBLE $b\bar{b}q\bar{q}$ STATE
Authors: GUO F.-K. , SHEN P.-N. , CHIANG H.-C. , PING R.-G.
Published: June 2005

π+π- transitions of heavy quarkonia, especially the ϒ(3S)→ϒ(1S)π+π- decay process are studied. An effective Lagrangian is employed and the S wave ππ final state interaction (FSI) is included in the framework of the Chiral Unitary Theory (ChUT). It is found that when an additional intermediate state with JP=1+ and I=1 is introduced, the experimental data can be well-explained, and a consistent description of bottomonium π+π- transitions can be obtained. As a consequence, the mass and the width of the intermediate state are predicted. From the quark content analysis, this state should be a [Formula: see text] state.
A QUARK MESON COUPLING MODEL WITH DENSITY- AND TEMPERATURE-DEPENDENT QUARK MASSES
Authors: QIAN WEI LIANG , SU RU-KENG
Published: June 2005

Based on the quark mass density- and temperature- dependent model we suggest a model for nuclear matter where the meson field is introduced to be directly coupled to the quarks. The dynamic formation of the nucleon bag, the saturation properties of nuclear matter as well as equation of state for this model are studies.
MEASUREMENT OF THE HADRONIC CROSS SECTION VIA RADIATIVE RETURN AT DAΦNE
Authors:   Presented for the KLOE Collaboration: The KLOE Collaboration: A. Aloisio, F. Ambrosino, A. Antonelli, M. Antonelli, C. Bacci, G. Bencivenni, S.Bertolucci, C. Bini, C. Bloise, V. Bocci, F. Bossi, P. Branchini, S. A. Bulychjov, R. Caloi, P. Campana, G. Capon, T. Capussela, G. Carboni, G. Cataldi, F. Ceradini, F. Cervelli, F. Cevenini, G. Chiefari, P. Ciambrone, S. Conetti, E. De Lucia, P. De Simone, G. De Zorzi, S. Dell'Agnello, A. Denig, A. Di Domenico, C. Di Donato, S. Di Falco, B. Di Micco, A. Doria, M. D, DENIG ACHIM G.
Published: June 2005

The cross section σ(e+e-→π+π-γ) has been measured with the KLOE detector at the electron-positron collider DAΦNE, at an energy W=mϕ=1.02 GeV . We perform this measurement as a function of the π+π- invariant mass, Mππ. The photon in the above process is due to Initial State Radiation. Dividing by a theoretical radiator function, we obtain the cross section σ(e+e-→π+π-) for the mass range [Formula: see text] with an overall accuracy of 1.3%. We also calculate the hadronic contribution of the two-pion channel to the anomalous magnetic moment of the muon for the given mass range: [Formula: see text].
DETERMINATION OF QCD RUNNING COUPLING CONSTANT IN NNLO APPROXIMATION, USING COMPLETE RG IMPROVEMENT
Authors: MIRJALILI A. , KHORRAMIAN ALI N. , TEHRANI S. ATASHBAR
Published: June 2005

To obtain the improved QCD predictions for the moments of the xF3 structure function in νN scattering, three-loop Wilson coefficients with the corresponding NNLO anomalous dimension coefficients is used. A comparison between QCD predictions and the xF3 data of the CCFR collaboration has been done in which the Bernstein Polynomial method is used in the complete renormalization group improvement approach. A direct fits for [Formula: see text] over the corresponding range of Q2 with five effective quark flavours, is performed.
HEAVY ANTIQUARK PENTAQUARKS IN THE CM AND GB MODELS
Authors: MALTMAN KIM
Published: June 2005

The splittings between positive parity pentaquarks containing a single heavy (c, b) antiquark and four light (u, d) quarks are investigated in models having spin-dependent interactions generated by either effective Goldstone boson exchange or effective color magnetic exchange. Model-independent features of these splittings are emphasized. Overlaps to the "fall-apart" decay configurations ND, ND* or NB, NB*, relevant to decay couplings for the various 2-body pentaquark decays, are also computed.
OBSERVATION OF $p\bar{p}$, $p\bar{\Lambda}$, $K^-\bar{\Lambda}$ NEAR-THRESHOLD ENHANCEMENT AT BES
Authors:   For the BES Collaboration., YANG HONGXUN
Published: June 2005

We observe a narrow enhancement near 2mp in the invariant mass spectrum of [Formula: see text] pairs from radiative [Formula: see text] decays. In the case of S-wave fit, the peak mass is below 2mp at [Formula: see text] and the total width is Γ<30MeV at the 90% confidence level. And we also find near-threshold enhancement in the invariant mass spectrum of [Formula: see text] in [Formula: see text] decays. The mass is m=2075±12(stat)±5(syst)MeV and width is Γ=90±35(stat)±9(syst)MeV. A [Formula: see text] near-threshold enhancement is also studied and it has m=1.50~1.65GeV, Γ=70~110MeV with [Formula: see text].
CHARGED PARTICLE DYNAMICS IN THE FIELD OF A SLOWLY ROTATING COMPACT STAR
Authors: MIRZA BABUR M.
Published: June 2005

We study the dynamics of a charged particle in the field of a slowly rotating compact star in the gravitoelectromagnetic approximation to the geodesic equation. The star is assumed to be surrounded by an ideal, highly conducting plasma (taken as a magneto-hydrodynamic fluid) with a stationary, axially symmetric electromagnetic field. The general relativistic Maxwell equations are solved to obtain the effects of the background spacetime on the electromagnetic field in the linearized Kerr spacetime. The equations of motion are then set up and solved numerically to incorporate the gravitational as well as the electromagnetic effects. The analysis shows that in the slow rotation approximation, the frame dragging effects on the electromagnetic field are absent. However the particle is directly effected by the rotating gravitational source such that close to the star the gravitational and electromagnetic field produce contrary effects on the particle trajectories.
Cytochrome P4502E1 primes macrophages to increase TNF-α production in response to lipopolysaccharide
Authors: Cao Qi , Mak Ki M. , Lieber Charles S.
Published: June 2005

Kupffer cells become activated in response to elevated levels of LPS during ethanol feeding, but the role of ethanol in the molecular processes of activation remains unclear. Because cytochrome P4502E1 (CYP2E1) is upregulated in Kupffer cells after ethanol, we hypothesized that this effect primes Kupffer cells, sensitizing them to increase TNF-α production in response to LPS. However, cultured Kupffer cells rapidly lose their CYP2E1. This difficulty was overcome by transfecting CYP2E1 to RAW 264.7 macrophages. Macrophages with stable increased CYP2E1 expression (E2) displayed increased levels of CD14/Toll-like receptor 4, NADPH oxidase and H2O2, accompanied by activation of ERK1/2, p38, and NF-κB. These increases primed E2 cells, sensitizing them to LPS stimuli, with amplification of LPS signaling, resulting in increased TNF-α production. Diphenyleneiodonium, a NADPH oxidase inhibitor, and diallyl sulfide, a CYP2E1 inhibitor, decreased approximately equally H2O2levels in E2 cells, suggesting that NADPH oxidase and CYP2E1 contribute equally to H2O2generation. Because CYP2E1 expression also enhanced the levels of the membrane localized NADPH oxidase subunits p47phoxand p67phox, thereby contributing to the oxidase activation, it may augment H2O2generation via this mechanism. H2O2, derived in part from NADPH and CYP2E1, activated ERK1/2 and p38. ERK1/2 stimulated TNF-α production via activation of NF-κB, whereas p38 promoted TNF-α production by stabilizing TNF-α mRNA. Oxidant generation after CYP2E1 overexpression appears to be central to macrophage priming and their sensitization to LPS. Accordingly, CYP2E1 priming could explain the sensitization of Kupffer cells to LPS activation by ethanol, a critical early step in alcoholic liver disease.
Chemical Identification and Characterization of DJ-1 Protein in Human Fetal Amygdala
Authors: Hepner Felix , Engidawork Ephrem , Ulfig Norbert , Pollak Arnol , Lubec Gert
Published: June 2005

Performing protein profiling in fetal human amygdala, we detected DJ-1 protein (PARK7). As DJ-1 and its isoforms are of major importance in cell biology, transformation and neurodegenerative diseases, like Parkinson’s disease, we decided to chemically unambiguously identify and characterize this protein and possible posttranslational modifications by matrix-assisted laser desorption/ionization mass spectrometry followed by tandem mass spectrometry, being a reliable analytical tool independent of antibody availability and specificity.
Evaluation of the BD Phoenix Automated Microbiology System for Identification and Antimicrobial Susceptibility Testing of Common Clinical Isolates
Authors: Liu Z.K. , Ling T.K. , Cheng A.F.
Published: June 2005

Objective: To evaluate the accuracy and reliability of the BD Phoenix Automated Microbiology System for identification (ID) and antimicrobial susceptibility testing (AST) of Gram-positive and Gram-negative isolates. Materials and Methods: The ID of 291 Gram-negative and 158 Gram-positive clinical isolates were evaluated by the system. The AST of 252 Gram-negative and 151 Gram-positive isolates with correct ID were then evaluated. The results were compared with those of the API ID system and the microbroth dilution method. All discrepant results were repeated for verification. Results: Over 90% Gram-negative and Gram-positive isolates were correctly identified to species or genus level by the Phoenix system. The minimum inhibitory concentration agreement rates between the Phonenix and the microbroth dilution methods within ±1 dilution ranged from 87.3 to 97.6% for Gram-negative isolates, and from 50 to 100% for Gram-positive isolates. For Gram-positive isolates, vancomycin had significant low minimum inhibitory concentration agreement rates. Conclusions: Overall, the results indicate that the Phoenix system is a reliable system. It could provide accurate ID and AST results for routine clinical laboratories.
E-Test: An Alternative Method for Susceptibility Testing of Mycobacterium tuberculosis
Authors: Akcali Sinem , Cicek Candan , Surucuoglu Suheyla , Ozbakkaloglu Beril
Published: June 2005

Objective: The purpose of this study was to compare the agar proportion method with the E-test method for susceptibility testing of Mycobacterium tuberculosis.Materials and Methods: A total of 100 isolates were tested for isoniazid, rifampin, streptomycin and ethambutol susceptibility using an indirect-proportion method as well as the E-test method. Results:Categorical agreement between the methods was 100% for isoniazid, rifampin, streptomycin, and ethambutol. Conclusion: The E-test method appears to be an alternative method to agar proportion for testing the susceptibility of M. tuberculosis isolates to the first-line antituberculous agents.
A 20-Year Experience of Combined Liver/Kidney Transplantation for Primary Hyperoxaluria (PH1): The European PH1 Transplant Registry Experience 1984–2004
Authors: Jamieson Neville V.
Published: June 2005

Primary hyperoxaluria (PH1) is a condition caused by a hepatic-based enzyme defect which can lead to renal failure due to oxalate stone disease, obstructive uropathy and nephrocalcinosis. It has been shown that the underlying metabolic defect can be corrected by liver transplantation and in most cases (renal failure having already occurred) is accompanied by a kidney graft. This paper describes the current results of 127 liver transplants performed in 117 patients over a 20-year period from 1984 to 2004 in 35 European centres. The mean age at onset of symptoms was 5.6 ± 7.8 years and the mean age at which a diagnosis was made was 8.8 ± 9.5 years. The diagnosis was confirmed by liver biopsy proven decreased AGT activity in 68% of cases, hyperoxaluria in 74%, hyperglycolicaciduria in 37% and hyperoxalaemia in 50%. Patients were transplanted at a mean age of 16.5 ± 11.4 years following a period of dialysis of 3.2 ± 3.2 years (range 0–14.4 years). 1-, 5- and 10-year patient survival values were 86, 80 and 69%, respectively, and liver graft survival rates of 80, 72 and 60% at the same time intervals. There have been 27 deaths and 10 liver retransplants have been carried out. Patient outcomes are improved when prolonged periods on dialysis and the complications of systemic oxalosis have not occurred.
Critical Role of Mst1 in Vascular Remodeling After Injury
Authors: Ono Hiroki , Ichiki Toshihiro , Ohtsubo Hideki , Fukuyama Kae , Imayama Ikuyo , Hashiguchi Yasuko , Sadoshima Junichi , Sunagawa Kenji
Published: June 2005

Objective—

Apoptosis of vascular smooth muscle cells (VSMCs) is observed in chronic vascular lesions such as atherosclerotic plaques and is believed to contribute to the vascular remodeling process. Mst1 is a ubiquitously expressed serine/threonine kinase known to be activated in response to a wide variety of nonphysiological apoptotic stimuli. However, little is known of the physiological function of Mst1, and its role in VSMCs has never been examined.

Methods and Results—

Treatment of VSMCs with staurosporine induced apoptosis and cleavage of Mst1, which is a marker of its activation, as well as activation of caspase 3. Adenovirus-mediated overexpression of wild-type Mst1 (AdMst1) in VSMCs increased apoptotic cells with activation of caspase 3. Mst1 was induced and activated in the balloon-injured rat carotid artery. Infection with AdMst1 in balloon-injured rat carotid artery suppressed neointimal formation compared with infection with AdLacZ. Infection with AdMst1 significantly increased the apoptotic cell number in the neointima compared with infection with AdLacZ without affecting BrdU incorporation.

Conclusion—

Our results suggest that Mst1 plays an important role in the induction of apoptosis of VSMCs, mediating the vascular remodeling process, and may be a potential therapeutic target for vascular proliferative diseases.
Recommendations for Comprehensive Stroke Centers
Authors: Alberts Mark J. , Latchaw Richard E. , Selman Warren R. , Shephard Timothy , Hadley Mark N. , Brass Lawrence M. , Koroshetz Walter , Marler John R. , Booss John , Zorowitz Richard D. , Croft Janet B. , Magnis Ellen , Mulligan Diane , Jagoda Andrew , O’Connor Robert , Cawley C. Michael , Connors J.J. , Rose-DeRenzy Jean A. , Emr Marian , Warren Margo , Walker Michael D.
Published: June 2005

Background and Purpose—

To develop recommendations for the establishment of comprehensive stroke centers capable of delivering the full spectrum of care to seriously ill patients with stroke and cerebrovascular disease. Recommendations were developed by members of the Brain Attack Coalition (BAC), which is a multidisciplinary group of members from major professional organizations involved with the care of patients with stroke and cerebrovascular disease.

Summary of Review—

A comprehensive literature search was conducted from 1966 through December 2004 using Medline and Pub Med. Articles with information about clinical trials, meta-analyses, care guidelines, scientific guidelines, and other relevant clinical and research reports were examined and graded using established evidence-based medicine approaches for therapeutic and diagnostic modalities. Evidence was also obtained from a questionnaire survey sent to leaders in cerebrovascular disease. Members of BAC reviewed literature related to their field and graded the scientific evidence on the various diagnostic and treatment modalities for stroke. Input was obtained from the organizations represented by BAC. BAC met on several occasions to review each specific recommendation and reach a consensus about its importance in light of other medical, logistical, and financial factors.

Conclusions—

There are a number of key areas supported by evidence-based medicine that are important for a comprehensive stroke center and its ability to deliver the wide variety of specialized care needed by patients with serious cerebrovascular disease. These areas include: (1) health care personnel with specific expertise in a number of disciplines, including neurosurgery and vascular neurology; (2) advanced neuroimaging capabilities such as MRI and various types of cerebral angiography; (3) surgical and endovascular techniques, including clipping and coiling of intracranial aneurysms, carotid endarterectomy, and intra-arterial thrombolytic therapy; and (4) other specific infrastructure and programmatic elements such as an intensive care unit and a stroke registry. Integration of these elements into a coordinated hospital-based program or system is likely to improve outcomes of patients with strokes and complex cerebrovascular disease who require the services of a comprehensive stroke center.
Chinese Civilisation
Authors: Chung Tan
Published: June 2005

Civilisation is usually not allotted the front seat in social science discourses except for being treated as a whipping boy. This is precisely what the ‘Clash-of-Civilisations’ school has done. Nevertheless, we should thank Professor Samuel Huntington of Harvard University for bringing ‘civilisation’ into sharp focus. Huntington and others have initiated a civilisational discourse in the world forum on international political affairs, inviting much echo and more critique on their Great Divide between ‘us’ (the Western Judaic-Christian liberal-capitalist mainstream) and ‘them’ (all non-Western, non-Christian, particularly the Islamic and ‘Confucian-Chinese’ traditions) in the comity of nations and peoples. In anthropology, the ‘culturalists’ have been challenging the sociologists for many decades. I worked exactly throughout this challenging period as a culturalist or civilisationalist in a small circle of Chinese studies in Delhi from the mid-sixties up to 1999. My most enthusiastic sympathiser and supporter is the very person whom we are remembering today. How I wish Giri Deshingkar were standing here in my place, instead of dedicating this talk to his memory!
Role of Ideas in the Survival of the Chinese Communist Party
Authors: Khan Waheed A.
Published: June 2005

Three major questions are raised in this paper. First, why did the Dengist leadership pursue the ‘specific’ reform policies that ultimately proved to be successful? Second, how could the Chinese Communist party (CCP) legitimise its role in society after compromising on most of the socialist agenda? And third, why has the economic liberalisation not led to the democratic form of government in China even after more than two decades of reforms? By using Berman’s ideational approach (Berman 1998), it is found that a specific variant of socialism, which also allowed some of the capitalist tendencies, became institutionalised in the early history of the CCP. The ‘programmatic beliefs’ and ‘policy legacies’, which characterise this variant of socialism in China, constrained and guided the Dengist leadership to pursue the reforms that were compatible with Chinese conditions. As these reforms were within the framework of the ‘programmatic beliefs’ of the CCP, the party did not face legitimacy crisis in the eyes of the Chinese people, and thus retained its power after reforms.
Hemchandra's Bharat Sangeet (1870) and the politics of poetry
Authors: Chaudhuri Rosinka
Published: June 2005

This article intends to examine the legacy of an unabashedly militant Hindu image that the poet Hemchandra Bandyopadhyay inaugurated at the very inception of nationalist and literary discourse in India in a famous poem called Bharat Sangeet (1870). Where was this prescient image, which would become fundamental to a certain type of anti-colonial politics, located in the relationship between nineteenth-century literature, militancy and the political imagination in Bengal?

A closer look at the conflicting pressures on the colonised cautions against a teleology which would see this poem as a precursor to a more pernicious strain of later Hindu nationalism while recognising, at the same time, that the dissemination of certain revolutionary ideals through a few influential literary texts inaugurated a philosophy of extremist politics in Bengal that travelled, in no time at all, from the literary arena into life.
Oncolytic measles virus in cutaneous T-cell lymphomas mounts antitumor immune responses in vivo and targets interferon-resistant tumor cells
Authors: Heinzerling Lucie , Künzi Valerie , Oberholzer Patrick A. , Kündig Thomas , Naim Hussein , Dummer Reinhard
Published: June 2005

Some cutaneous T-cell lymphomas, (CTCLs) clonal T cells are deficient in interferon signaling, making them promising targets for viral oncolysis. We evaluated cytopathic effects of measles virus (MV) in CTCL. CTCL cell lines and infiltrating lymphocytes in CTCL expressed MV receptors CD150 and CD46. In a phase 1 dose escalation trial a total of 16 injections of live MV, Edmonston-Zagreb vaccine strain, were given intratumorally to 5 patients with CTCL. Patients had antimeasles-serum antibodies and were pretreated with interferon-α to prevent uncontrolled virus spread. The well-tolerated treatment with MV resulted in clinical responses. Evaluation of biopsies, before and at 11 days after injection, by immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated local viral activity with positive staining for MV nucleoprotein (NP), an increase of the interferon γ (IFN-γ)/CD4 and IFN-γ/CD8 mRNA ratios and a reduced CD4/CD8 ratio. All patients demonstrated an increased antimeasles antibody titer after therapy. The data demonstrate that CTCLs are promising targets for an MV-based oncolytic therapy.
Platelets express functional Toll-like receptor-4
Authors: Andonegui Graciela , Kerfoot Steven M. , McNagny Kelly , Ebbert Kirsten V. J. , Patel Kamala D. , Kubes Paul
Published: June 2005

Profound thrombocytopenia occurs in humans with sepsis and in mice administered lipopolysaccharide (LPS). Growing evidence indicates that platelets may contribute to these abnormalities, but whether that is a direct result of LPS activation of platelets or an indirect result of other inflammatory mechanisms remains unclear. Here we demonstrate that although platelets do not increase P-selectin expression in response to LPS, platelets bind more avidly to fibrinogen under flow conditions in a Toll-like receptor-4 (TLR4)-dependent manner. In addition, we find that CD41+ megakaryocytes grown from fetal livers and adult circulating platelets express significant amounts of TLR4. LPS induced thrombocytopenia in wild-type mice but not in TLR4-deficient (TLR4def) mice. Wild-type platelets accumulated in the lungs of wild-type mice in response to LPS; TLR4def platelets did not. However, wild-type platelets did not accumulate in the lungs of LPS-treated TLR4def mice. Neutrophils also accumulated in the lungs, and this preceded platelet accumulation. Neutrophil depletion completely abolished LPS-induced platelet sequestration into the lungs, but platelet depletion did not affect neutrophil accumulation. Thus, our data show for the first time that platelets do express functional levels of TLR4, which contribute to thrombocytopenia through neutrophil-dependent pulmonary sequestration in response to LPS. (Blood. 2005;106:2417-2423)
Molecular and Cellular Biology Animations: Development and Impact on Student Learning
Authors: McClean Phillip , Johnson Christina , Rogers Roxanne , Daniels Lisa , Reber John , Slator Brian M. , Terpstra Jeff , White Alan
Published: June 2005

Educators often struggle when teaching cellular and molecular processes because typically they have only two-dimensional tools to teach something that plays out in four dimensions. Learning research has demonstrated that visualizing processes in three dimensions aids learning, and animations are effective visualization tools for novice learners and aid with long-term memory retention. The World Wide Web Instructional Committee at North Dakota State University has used these research results as an inspiration to develop a suite of high-quality animations of molecular and cellular processes. Currently, these animations represent transcription, translation, bacterial gene expression, messenger RNA (mRNA) processing, mRNA splicing, protein transport into an organelle, the electron transport chain, and the use of a biological gradient to drive adenosine triphosphate synthesis. These animations are integrated with an educational module that consists of First Look and Advanced Look components that feature captioned stills from the animation representing the key steps in the processes at varying levels of complexity. These animation-based educational modules are available via the World Wide Web at http://vcell.ndsu.edu/animations . An in-class research experiment demonstrated that student retention of content material was significantly better when students received a lecture coupled with the animations and then used the animation as an individual study activity.
“Shrink Wrapping” Lectures: Teaching Cell and Molecular Biology within the Context of Human Pathologies
Authors: Guilford William H.
Published: June 2005

Students are most motivated and learn best when they are immersed in an environment that causes them to realize why they should learn. Perhaps nowhere is this truer than when teaching the biological sciences to engineers. Transitioning from a traditionally mathematics-based to a traditionally knowledge-based pedagogical style can challenge student learning and engagement. To address this, human pathologies were used as a problem-based context for teaching knowledge-based cell biological mechanisms. Lectures were divided into four modules. First, a disease was presented from clinical, economic, and etiological standpoints. Second, fundamental concepts of cell and molecular biology were taught that were directly relevant to that disease. Finally, we discussed the cellular and molecular basis of the disease based on these fundamental concepts, together with current clinical approaches to the disease. The basic science is thus presented within a “shrink wrap” of disease application. Evaluation of this contextual technique suggests that it is very useful in improving undergraduate student focus and motivation, and offers many advantages to the instructor as well.
Profiling dendritic cell maturation with dedicated microarrays
Authors: McIlroy Dorian , Tanguy-Royer Séverine , Le Meur Nolwenn , Guisle Isabelle , Royer Pierre-Joseph , Léger Jean , Meflah Khaled , Grégoire Marc
Published: June 2005

Dendritic cell (DC) maturation is the process by which immature DC in the periphery differentiate into fully competent antigen-presenting cells that initiate the T cell response. However, DC respond to many distinct maturation stimuli, and different types of mature DC induce qualitatively different T cell responses. As DC maturation involves the coordinated regulation of hundreds of genes, comprehensive assessment of DC maturation status would ideally involve monitoring the expression of all of these transcripts. However, whole-genome microarrays are not well-suited for routine phenotyping of DC, as the vast majority of genes represented on such chips are not relevant to DC biology, and their cost limits their use for most laboratories. We therefore developed a DC-dedicated microarray, or “DC Chip”, incorporating probes for 121 genes up-regulated during DC maturation, 93 genes down-regulated during maturation, 14 DC-specific genes, and 90 other genes with known or probable immune functions. These microarrays were used to study the kinetics of DC maturation and the differences in maturation profiles among five healthy donors after stimulation with tumor necrosis factor-α + polyI:C. Results obtained with the DC Chip were consistent with flow cytometry, enzyme-linked immunosorbent assay, and real-time polymerase chain reaction, as well as previously published data. Furthermore, the coordinated regulation of a cluster of genes (indoleamine dioxygenase, kynureninase, kynurenine monoxygenase, tryptophanyl tRNA synthetase, and 3-hydroxyanthranilate 3,4-dioxygenase) involved in tryptophan metabolism was observed. These data demonstrate the use of the DC Chip for monitoring the molecular processes involved in the orientation of the immune response by DC.
Chemokine expression during development of fibrosis versus resolution in a murine model of granulomatous experimental autoimmune thyroiditis
Authors: Chen Kemin , Wei Yongzhong , Alter Adam , Sharp Gordon C , Braley-Mullen Helen
Published: June 2005

Severe granulomatous eperimental autoimmune thyroiditis (G-EAT) in DBA/1 or CBA/J wild type (WT) mice at day 19 progresses to fibrosis by day 35, but severe G-EAT in DBA/1 interferon (IFN)-γ−/− mice or less-severe G-EAT at day 19 in WT mice resolves by day 35. To study the role of chemokines in autoimmune diseases and fibrosis, profiles of chemokines and chemokine receptors were analyzed in DBA/1 WT versus IFN-γ−/− and CBA/J thyroids, which have distinct outcomes of autoimmune inflammation. Gene expression of CXC chemokine ligand 1 (CXCL1) and CXC chemokine receptor 2 (CXCR2) paralleled neutrophil infiltration and thyrocyte destruction in DBA/1 WT or CBA/J thyroids, and gene expression of CC chemokine ligand 11 (CCL11), CCL8, and CC chemokine receptor 3 paralleled eosinophil infiltration in IFN-γ−/− thyroids. Gene and protein expression of CXCL10, CXCL9, and CXCR3 was significantly lower in IFN-γ−/− compared with DBA/1 WT thyroids. Moreover, immunostaining showed that CXCL10 was expressed by thyrocytes and inflammatory cells, and strong expression of CXCL10 by thyrocytes was as early as day 7. High expression of CCL2 was only observed in severely destroyed DBA/1 WT or CBA/J thyroids, which would develop fibrosis. Thus, the differential expression of chemokines may direct distinct cellular populations in DBA/1 WT versus IFN-γ−/− thyroids. Up-regulation of CXCL10 by thyrocytes suggests its role in regulating the recruitment of specific subsets of activated lymphocytes to the thyroid during autoimmune inflammation. The early expression of CXCL1, CXCL10, and CCL2 may suggest their involvement in the initiation and perpetuation of disease in severe G-EAT thyroids, which progress to fibrosis.
Human Retinal Progenitor Cells Grown as Neurospheres Demonstrate Time‐Dependent Changes in Neuronal and Glial Cell Fate Potential
Authors: GAMM DAVID M. , NELSON AARON D. , SVENDSEN CLIVE N.
Published: June 2005

Abstract: The spatiotemporal birth order of the seven major classes of retinal cells is highly conserved among vertebrates. During retinal development, long projection neurons (ganglion cells) are produced first from resident progenitors, followed by the appearance of retinal interneurons, photoreceptors, and Muller glia. This sequence is maintained through the complex orchestration of cell‐intrinsic and cell‐extrinsic events and factors, including local influences between neighboring cells. Here we asked whether cultures of human prenatal retinal cells might also yield different ratios of cell types based on gestational age and time spent in vitro, thus recapitulating in vivo development. An established chopping technique was used to passage human prenatal retinal cells as neurospheres, avoiding the use of proteases and preserving cell‐cell contacts and native microenvironments present in vivo. Retinal neurospheres cultured in this manner demonstrated specific patterns of growth over a limited time period, possibly reflecting trends in normal retinal development. Upon differentiation, immunocytochemical analysis revealed that retinal neurospheres produce predominantly glial cells with increasing gestational age and time in culture. Conversely, the percentage of βIII tubulin‐positive neurons declined over time. This provides information for optimizing culture systems aimed at the study of human retinal development and the generation of specific retinal cell types for therapeutic use or drug testing.
Evolutional Analysis in Determining Pathogenic versus Nonpathogenic Mutations of ATPase 6 in Human Mitochondriopathy
Authors: TZEN CHIN‐YUAN , WU TSU‐YEN
Published: June 2005

Abstract: Because mitochondrial ATPase 6 plays an important role in ATP synthesis, mutations affecting ATPase 6 can undoubtedly cause human diseases. In contrast, the ATPase 6 gene is known to be a fast‐evolving gene and has generated enough polymorphisms to allow identity investigation for forensic casework. To investigate these seemingly opposite views, we analyzed amino acid sequences of ATPase 6 in at least 1,266 humans, 102 mammals, and 213 vertebrates. The result showed that the amino acids of human ATPase 6 could be divided into the following four groups. Amino acid residue 192 (affected by alteration at nt 9101) and 79 other residues were variable, and therefore substitutions of these residues would not be pathogenic. Amino acid residue 156 (affected by alteration at nt 8993) and 93 other residues were conserved in Homo sapiens, but not in Mammalia. Therefore, they were potentially pathogenic if altered. Function studies would be necessary to confirm their role in pathogenesis. Amino acid residue 217 (affected by alteration at nt 9176) and 9 other residues were conserved across all species, including S. cerevisiae and E. coli. Mutations involving these residues would be pathogenic, some of which might even be life threatening. The remainder (42 residues) were conserved in Mammalia, but not in yeast and E. coli. They were probably pathogenic if mutated. The classification proposed in this study may, therefore, provide an algorithm for a diagnostic approach when a newly identified change of ATPase 6 is suspected for human mitochondriopathy.
Anti‐Inflammatory and Antioxidative Effects of Propofol on Lipopolysaccharide‐Activated Macrophages
Authors: CHEN RUEI‐MING , CHEN TYNG‐GUEY , CHEN TA‐LIANG , LIN LI‐LING , CHANG CHIA‐CHEN , CHANG HWA‐CHIA , WU CHIH‐HSIUNG
Published: June 2005

Abstract: Sepsis is a serious and life‐threatening syndrome that often occurs in intensive care unit (ICU) patients. During sepsis, inflammatory cytokines and nitric oxide (NO) can be overproduced, causing tissue and cell injury. Propofol is an intravenous agent used for sedation of ICU patients. Our previous study showed that propofol has immunosuppressive effects on macrophage functions. This study was designed to evaluate the anti‐inflammatory and antioxidative effects of propofol on the biosyntheses of tumor necrosis factor α (TNF‐α), interleukin 1β (IL‐1β), IL‐6, and NO in lipopolysaccharide (LPS)‐ activated macrophages. Exposure to a therapeutic concentration of propofol (50 μM), LPS (1 ng/mL), or a combination of these two drugs for 1, 6, and 24 h was not cytotoxic to the macrophages. ELISA revealed that LPS increased macrophage TNF‐α, IL‐1β, and IL‐6 protein levels in a time‐dependent manner, whereas propofol significantly reduced the levels of LPS‐enhanced TNF‐α, IL‐1β, and IL‐6 proteins. Data from RT‐PCR showed that LPS induced TNF‐α, IL‐1β, and IL‐6 mRNA, but propofol inhibited these effects. LPS also increased NO production and inducible nitric oxide synthase (iNOS) expression in macrophages. Exposure of macrophages to propofol significantly inhibited the LPS‐induced NO biosynthesis. The present study shows that propofol, at a therapeutic concentration, has anti‐inflammatory and antioxidative effects on the biosyntheses of TNF‐α, IL‐1β, IL‐6, and NO in LPS‐activated macro‐phages and that the suppressive effects are exerted at the pretranslational level.
Antioxidant N‐Acetylcysteine Blocks Nerve Growth Factor‐Induced H2O2/ERK Signaling in PC12 Cells
Authors: YANG LIANG‐YO , KO WUN‐CHANG , LIN CHUN‐MAO , LIN JIA‐WEI , WU JEN‐CHINE , LIN CHIEN‐JU , CHENG HUEY‐HWA , SHIH CHWEN‐MING
Published: June 2005

Abstract: We investigated whether H2O2, superoxide, and ERK participate in nerve growth factor (NGF)‐induced signaling cascades and whether antioxidant N‐acetylcysteine (NAC) regulates these NGF‐induced responses. PC12 cells were cultured in medium containing NGF or vehicle with or without NAC pretreatment, and the intracellular H2O2 and superoxide levels and the amount of phosphorylated ERK were evaluated by flow cytometry and Western blotting, respectively. We found that NGF increased intracellular H2O2 concentration and activated ERK but failed to affect intracellular superoxide level. Moreover, NAC counteracted these NGF‐induced responses. These findings demonstrate that NAC blocks the NGF‐induced H2O2/ERK signaling in PC12 cells.
Inhibitory Effects of a Rice Hull Constituent on Tumor Necrosis Factor α, Prostaglandin E2, and Cyclooxygenase‐2 Production in Lipopolysaccharide‐Activated Mouse Macrophages
Authors: HUANG SHENG‐TUNG , CHEN CHIEN‐TSU , CHIENG KUR‐TA , HUANG SHIH‐HAO , CHIANG BEEN‐HUANG , WANG LENG‐FANG , KUO HSIEN‐SAW , LIN CHUN‐MAO
Published: June 2005

Abstract: Isovitexin, isolated from rice hull of Oryza sativa, has been characterized as a potent antioxidant. Its antioxidant activity, determined on the basis of inhibition of lipid peroxidation by the Fenton reaction, was comparable with that of α‐tocopherol, a well‐established antioxidant. Isovitexin was able to reduce the amount of hydrogen peroxide production induced by lipopolysaccharide (LPS) in mouse macrophage RAW264.7 cells. In this study, we assessed its effects on the production of tumor necrosis factor α (TNF‐α), prostaglandin E2 (PGE2), and the expression of cyclooxygenase‐2 (COX‐2) in LPS‐activated RAW 264.7 macrophages. Isovitexin inhibited the release of TNF‐α, a proinflammatory cytokine, upon LPS activation with a 50% inhibitory concentration (IC50) of 78.6 μM. Isovitexin markedly reduced LPS‐stimulated PGE2 production in a concentration‐dependent manner, with an IC50 of 80.0 μM. The expression of COX‐2 was also inhibited by isovitexin treatment. Our results suggest that suppression of ROS‐mediated COX‐2 expression by isovitexin is beneficial in reducing inflammation and carcinogenesis.
Phase I Pharmacokinetic and Pharmacodynamic Study of 17-Allylamino, 17-Demethoxygeldanamycin in Patients With Advanced Malignancies
Authors: Banerji Udai , O'Donnell Anne , Scurr Michelle , Pacey Simon , Stapleton Sarah , Asad Yasmin , Simmons Laura , Maloney Alison , Raynaud Florence , Campbell Maeli , Walton Michael , Lakhani Sunil , Kaye Stanley , Workman Paul , Judson Ian
Published: June 2005

Purpose

To study the toxicity and pharmacokinetic-pharmacodynamic profile of 17-allylamino, 17- demethoxygeldanamycin (17-AAG) and to recommend a dose for phase II trials.

Patients and Methods

This was a phase I study examining a once-weekly dosing schedule of 17-AAG. Thirty patients with advanced malignancies were treated.

Results

The highest dose level reached was 450 mg/m2/week. The dose-limiting toxicities (DLTs) encountered were grade 3 diarrhea in three patients (one at 320 mg/m2/week and two at 450 mg/m2/week) and grade 3 to 4 hepatotoxicity (AST/ALT) in one patient at 450 mg/m2/week. Two of nine DLTs were at the highest dose level. Two patients with metastatic melanoma had stable disease and were treated for 15 and 41 months, respectively. The dose versus area under the curve-relationship for 17-AAG was linear (r2 = .71) over the dose range 10 to 450 mg/m2/week, with peak plasma concentrations of 8,998 μg/L (standard deviation, 2,881) at the highest dose level. After the demonstration of pharmacodynamic changes in peripheral blood leukocytes, pre- and 24 hours post-treatment, tumor biopsies were performed and demonstrated target inhibition (c-RAF-1 inhibition in four of six patients, CDK4 depletion in eight of nine patients and HSP70 induction in eight of nine patients) at the dose levels 320 and 450 mg/m2/week. It was not possible to reproducibly demonstrate these changes in biopsies taken 5 days after treatment.

Conclusion

It has been possible to demonstrate that 17-AAG exhibits a tolerable toxicity profile with therapeutic plasma concentrations and target inhibition for 24 hours after treatment and some indications of clinical activity at the dose level 450 mg/m2/week. We recommend this dose for phase II clinical trials.
Phase III Randomized Multicenter Study of a Humanized Anti-CD33 Monoclonal Antibody, Lintuzumab, in Combination With Chemotherapy, Versus Chemotherapy Alone in Patients With Refractory or First-Relapsed Acute Myeloid Leukemia
Authors: Feldman Eric J. , Brandwein Joseph , Stone Richard , Kalaycio Matt , Moore Joseph , O'Connor Julie , Wedel Nancy , Roboz Gail J. , Miller Carole , Chopra Raj , Jurcic Joseph C. , Brown Randy , Ehmann W. Christopher , Schulman Philip , Frankel Stanley R. , De Angelo Daniel , Scheinberg David
Published: June 2005

Purpose

Lintuzumab (HuM195) is an unconjugated humanized murine monoclonal antibody directed against the cell surface myelomonocytic differentiation antigen CD33. In this study, the efficacy of lintuzumab in combination with induction chemotherapy was compared with chemotherapy alone in adults with first relapsed or primary refractory acute myeloid leukemia (AML).

Patients and Methods

Patients with relapsed or primary resistant AML (duration of first response, zero to 12 months) were randomly assigned to receive either mitoxantrone 8 mg/m2, etoposide 80 mg/m2, and cytarabine 1 g/m2 daily for 6 days (MEC) in combination with lintuzumab 12 mg/m2, or MEC alone. Overall response, defined as the rate of complete remission (CR) and CR with incomplete platelet recovery (CRp), was the primary end point of the study, with additional analyses of survival time and toxicity.

Results

A total of 191 patients were randomly assigned from November 1999 to April 2001. The percent CR plus CRp with MEC plus lintuzumab was 36% v 28% in patients treated with MEC alone (P = .28). The overall median survival was 156 days and was not different in the two arms of the study. Apart from mild antibody infusion–related toxicities (fever, chills, and hypotension), no differences in chemotherapy-related adverse effects, including hepatic and cardiac dysfunction, were observed with the addition of lintuzumab to induction chemotherapy.

Conclusion

The addition of lintuzumab to salvage induction chemotherapy was safe, but did not result in a statistically significant improvement in response rate or survival in patients with refractory/relapsed AML.
Cultured Embryonic Hippocampal Neurons Deficient in Glucocorticoid (GC) Receptor: A Novel Model for Studying Nongenomic Effects of GC in the Neural System
Authors: Xiao Lin , Qi Aiqun , Chen Yizhang
Published: June 2005

Glucocorticoid (GC) acts through both genomic and nongenomic mechanisms. It affects the structure and function of the central nervous system, especially the hippocampus. Here we report an in vitro culture system that can yield embryonic hippocampal neurons deficient in the expression of GC receptor as demonstrated by immunoblotting, immunocytochemistry, and RT-PCR. Owing to this unique feature, those neuron preparations can serve as an ideal model for studying the nongenomic actions of GC on neural cells. In this study, we found that the Erk1/2, c-Jun N-terminal kinase (JNK), and p38 MAPKs were activated in these neurons by BSA-conjugated corticosterone within 15 min of treatment. This activation was not blocked by RU38486, spironolactone, or cycloheximide. Therefore, it is concluded that the activation of MAPKs observed here was due to the nongenomic action of GC. Furthermore, a 24-h incubation with corticosterone at concentrations ranged from 10−11–10−5m did not have an effect on the viability of GC receptor-deficient neurons.
Functional Effects of Transforming Growth Factor β on Adhesive Properties of Porcine Trophectoderm
Authors: Jaeger Laurie A. , Spiegel Aaron K. , Ing Nancy H. , Johnson Greg A. , Bazer Fuller W. , Burghardt Robert C.
Published: June 2005

In pigs, expression and amounts of biologically active TGFβs at the conceptus-maternal interface increase significantly as conceptuses elongate and begin the implantation process. Before their activation, secreted TGFβs are noncovalently associated with their respective, isoform-specific latency-associated peptides (LAPs), which contain the Arg-Gly-Asp (RGD) amino acid sequence that serves as a ligand for numerous integrins. Objectives of this study were to determine whether TGFβ1 increases production of fibronectin by porcine trophectoderm, whether porcine trophectoderm adheres specifically to fibronectin and LAP, and whether functional interactions between porcine trophectoderm and the two TGFβ-associated proteins, fibronectin and LAP, are integrin mediated. Porcine trophectoderm cells (pTr2) were cultured in presence of TGFβ1, LAP, or pan-neutralizing anti-TGFβ antibody; TGFβ specifically increased (P < 0.05) fibronectin mRNA levels, as determined by Northern and slot blot analyses. Immunofluorescence microscopy demonstrated a TGFβ-induced increase in fibronectin in pTr2 cells. In dispersed cell adhesion assays, adhesion of pTr2 cells to fibronectin was inhibited by an RGD-containing peptide (P < 0.05) and pTr2 cells attached to recombinant LAP but not to an LAP mutant, which contained an RGE sequence rather than the RGD site (P < 0.05). Fibronectin- and LAP-coated microbeads induced integrin activation at apical surfaces of both trophectoderm and uterine luminal epithelial cells, as indicated by aggregation and transmembrane accumulation of talin detected with immunofluorescence microscopy. Cell surface biotinylation and immunoprecipitation revealed integrin subunits αv and β1 on apical membranes of pTr2 cells. These results suggest multiple effects of TGFβ at the porcine conceptus-maternal interface, including integrin-mediated conceptus-maternal communication through LAP.
Simulation model of a screw liquid chiller for process industries using local heat transfer integration approach
Authors: Le C. V. , Bansal P. K. , Tedford J. D.
Published: June 2005

This paper presents a system simulation model of an oil-injected screw liquid chiller, where the refrigerant shell and tube heat exchangers are modelled following local heat transfer integration approach. All major components of the system are modelled in a modular format such as an oil-injected screw compressor, a shell and tube condenser, a flooded evaporator, and a high side-float valve. The simulation results are validated with the experimental data of a multiple-chiller plant at a process industry. The validated results show that the part-load ratio and the glycol-water temperature at the evaporator inlet affect the system performance considerably as compared to the temperature of cooling water entering the condenser.