bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of difficulties of some conceptual areas from electricity and magnetism using the Conceptual Survey of Electricity and Magnetism
Authors: Planinic Maja
Published: November 2006

The Conceptual Survey of Electricity and Magnetism (CSEM) covers a large conceptual domain and gives many opportunities for comparing the difficulties of different conceptual areas in electricity and magnetism. Six conceptual areas were identified in the CSEM that are represented by groups of four to six questions each. The CSEM was administered as a posttest to 84 Croatian students in a calculus-based general physics course at the University of Zagreb. The average difficulties in the six conceptual areas were compared to the average difficulties of the same conceptual areas of American students enrolled in algebra-based or calculus-based general physics courses. The difficulties of the conceptual areas show similar trends for the three groups of students. The most difficult area was found to be electromagnetic induction, followed by Newton’s laws in the context of electricity and magnetism, together with the electric potential and energy. The comparison of pretest and posttest results suggests that instruction in both algebra-based and calculus-based courses is not efficient in reducing the pretest difficulties of the conceptual areas; however, the impact of instruction differs among conceptual areas.
Rapid Emergence of Resistance to Linezolid during Linezolid Therapy of an
Enterococcus faecium
Infection
Authors: Seedat Jamela , Zick Günther , Klare Ingo , Konstabel Carola , Weiler Norbert , Sahly Hany
Published: November 2006

We report the emergence of linezolid resistance (MICs of 16 to 32 mg/liter) in clonally related vancomycin-susceptible and -resistant
Enterococcus faecium
isolates from an intensive care unit patient after 12 days of linezolid therapy. Only linezolid-susceptible isolates of the same clone were detected at 28 days after termination of linezolid therapy.
Comparative Bactericidal Activities of Daptomycin and Vancomycin against Glycopeptide-Intermediate
Staphylococcus aureus
(GISA) and Heterogeneous GISA Isolates
Authors: Wootton Mandy , MacGowan Alasdair P. , Walsh Timothy R.
Published: November 2006

Staphylococcus aureus
strains from the U.S. SENTRY Antimicrobial Surveillance Program, 2002-2003, glycopeptide-intermediate
S. aureus
(GISA) strains, and heterogeneous GISA (hGISA) strains were used to compare bactericidal activities of daptomycin and vancomycin using MICs and minimum bactericidal concentrations. Glycopeptide-susceptible
S. aureus
and hGISA strains were further studied by using time-kill curves. For all isolates, the daptomycin MIC
50
and MIC
90
are four times lower and the log drops in viable counts at 6 h and 24 h are significantly greater than those for vancomycin.
Resistance Mechanisms in an In Vitro-Selected Amoxicillin-Resistant Strain of
Helicobacter pylori
Authors: Co Edgie-Mark A. , Schiller Neal L.
Published: November 2006

We investigated the β-lactam resistance mechanism(s) of an in vitro-selected amoxicillin-resistant
Helicobacter pylori
strain (AmoxR). Our results demonstrated that resistance is due to a combination of amino acid substitutions in penicillin binding protein 1 (PBP1), HopB, and HopC identified in AmoxR, resulting in decreased affinity of PBP1 for amoxicillin and decreased accumulation of penicillin.
Cerebral vascular dysfunction in TallyHo mice: a new model of Type II diabetes
Authors: Didion Sean P. , Lynch Cynthia M. , Faraci Frank M.
Published: November 2006

The purpose of this study was to characterize vascular responses and to examine mechanisms of vascular dysfunction in TallyHo mice, a new polygenic model of Type II diabetes. Responses of cerebral arterioles and carotid arteries were examined in vivo by using a cranial window and in vitro by using tissue baths, respectively. Dilatation of cerebral arterioles (baseline diameter = 33 ± 1 μm) in response to acetylcholine, but not to nitroprusside, was markedly reduced ( P < 0.05) in TallyHo mice. Responses of cerebral arterioles to acetylcholine in TallyHo mice were restored to normal with polyethylene glycol-superoxide dismutase (100 U/ml; a superoxide scavenger). Responses to acetylcholine were also greatly impaired ( P < 0.05) in the carotid arteries from TallyHo mice. Phenylephrine- and serotonin-, but not to KCl- or U46619-, induced contraction was increased two- to fourfold ( P < 0.05) in carotid arteries of TallyHo mice. Responses to phenylephrine and serotonin were reduced to similar levels in the presence of Y-27632 (an inhibitor of Rho kinase; 3 μmol/l). These findings provide the first evidence that vascular dysfunction is present in TallyHo mice and that oxidative stress and enhanced activity of Rho kinase may contribute to altered vascular function in this genetic model of Type II diabetes.
Regional differences in glucose clearance: effects of insulin and resistance training on arm and leg glucose clearance in older hypertensive individuals
Authors: Reynolds Thomas H. , Supiano Mark A. , Dengel Donald R.
Published: November 2006

The purpose of this study was to compare insulin's ability to stimulate glucose uptake in the arm and leg in a group of older hypertensive individuals ( n = 13, 66 ± 2 yr old). We also examined the effect of a 4-mo whole body resistance-training (RT) program on arm and leg glucose clearance (GC) during a hyperinsulinemic-euglycemic clamp. During the hyperinsulinemic-euglycemic clamp, GC was assessed by simultaneous measurement of arm and leg blood flow (BF) and assessment of fractional glucose extraction (GE) in blood samples from the brachial artery, brachial vein, and popliteal vein. At baseline, a significant main effect (arm vs. leg) demonstrated greater GC and BF in the arm than in the leg ( P = 0.006 for GC and P = 0.012 for BF). Insulin significantly increased GE, BF, and GC in the arm and leg (main effects: P = 0.0001 for GE, P = 0.0001 for BF, and P = 0.0001 for GC) at baseline. However, the effect of insulin was similar in the arm and leg. After RT, a significant main effect (baseline vs. RT) demonstrated greater GE and GC in the leg ( P = 0.024 for GE and P = 0.053 for GE), but not in the arm ( P = 0.31 for GE and P = 0.14 for GC). No significant main effect (baseline vs. RT) for BF in the arm or leg was observed after RT. In conclusion, the greater GC in the arm than in the leg at baseline is primarily due to enhanced arm BF. Furthermore, whole body RT appears to increase GC in the leg but not in the arm.
Chlorpromazine Alters Cochlear Mechanics and Amplification: In Vivo Evidence for a Role of Stiffness Modulation in the Organ of Corti
Authors: Zheng Jiefu , Deo Niranjan , Zou Yuan , Grosh Karl , Nuttall Alfred L.
Published: November 2006

Although prestin-mediated outer hair cell (OHC) electromotility provides mechanical force for sound amplification in the mammalian cochlea, proper OHC stiffness is required to maintain normal electromotility and to transmit mechanical force to the basilar membrane (BM). To investigate the in vivo role of OHC stiffness in cochlear amplification, chlorpromazine (CPZ), an antipsychotic drug that alters OHC lateral wall biophysics, was infused into the cochleae in living guinea pigs. The effects of CPZ on cochlear amplification and OHC electromotility were observed by measuring the acoustically and electrically evoked BM motions. CPZ significantly reduced cochlear amplification as measured by a decline of the acoustically evoked BM motion near the best frequency (BF) accompanied by a loss of nonlinearity and broadened tuning. It also substantially reduced electrically evoked BM vibration near the BF and at frequencies above BF (≤80 kHz). The high-frequency notch (near 50 kHz) in the electrically evoked BM response shifted toward higher frequency in a CPZ concentration-dependent manner with a corresponding phase change. In contrast, salicylate resulted in a shift in this notch toward lower frequency. These results indicate that CPZ reduces OHC-mediated cochlear amplification probably via its effects on the mechanics of the OHC plasma membrane rather than via a direct effect on the OHC motor, prestin. Through modeling, we propose that with a combined OHC somatic and hair bundle forcing, the upward-shift of the ∼50-kHz notch in the electrically-evoked BM motion may indicate stiffness increase of the OHCs that is responsible for the reduced cochlear amplification.
Pulmonary Emphysema: When More is Less
Authors: Morris David G. , Sheppard Dean
Published: November 2006

Pulmonary emphysema results from the loss of intricate alveolar architecture and progressive simplification of small and highly effective gas-exchanging units into large, inefficient cyst-like spaces. Because of the loss of alveolar gas-exchanging units and the capillary bed within them, blood oxygen levels eventually fall and pressures within the pulmonary circulation rise. Recent insights from genetically manipulated mouse models have refined our understanding of the molecular events that prevent or promote the development of pulmonary emphysema. Capitalizing on an improved molecular understanding of emphysema with improved therapeutics has the potential to enhance both the survival and quality of life of patients with this common lung disease.
Fragile Histidine Triad Expression in Oral Squamous Cell Carcinoma and Precursor Lesions
Authors: Kujan Omar , Oliver Richard , Roz Luca , Sozzi Gabriella , Ribeiro Noel , Woodwards Robert , Thakker Nalin , Sloan Philip
Published: November 2006

Pupose: Fragile histidine triad (FHIT) expression in precursor oral lesions (POL) and oral squamous cell carcinomas (OSCC) was studied with regard to (a) the frequency of loss of FHIT expression, (b) whether loss of FHIT expression correlates with degree of dysplasia in POLs, (c) whether FHIT loss predicts high-risk POLs that are more likely to transform, and (d) whether FHIT loss in OSCCs correlates with survival.

Experimental Design: Ninety-four POLs and 86 OSCCs were immunostained for FHIT. Survival analysis was done for cases with validated clinical outcomes.

Results: By optimizing the immunostaining protocol, we found that FHIT is expressed in a distinctive strong nuclear and weak cytoplasmic pattern in oral tissues. Loss of FHIT expression was found in 42 of 94 (45%) POLs and in 66 of 86 (77%) OSCCs. We observed a statistically significant positive correlation between frequency of FHIT loss and increasing grade of dysplasia (χ2 = 13.8; degrees of freedom = 4; P = 0.008). Loss of FHIT expression in POLs that progressed to malignancy was more frequent than in those that did not [17 of 25 (68%) versus 12 of 29 (41.4%), respectively]. This difference was statistically significant (χ2 = 3.8; degrees of freedom = 1; P = 0.046). In OSCCs, loss of FHIT staining indicated a worse prognosis (survival rate, 36.2%) than when positive FHIT staining was observed (survival rate, 50%), but the difference was not statistically significant (P = 0.546, Kaplan-Meier, log-rank).

Conclusions: FHIT seems to localize to both nuclear and cytoplasmic domains. FHIT inactivation occurs early in oral carcinogenesis and may be useful molecular marker for progressive dysplastic oral lesions.
Down-Regulation of Insulin-Like Growth Factor I Receptor Activity by NVP-AEW541 Has an Antitumor Effect on Neuroblastoma CellsIn vitroandIn vivo
Authors: Tanno Barbara , Mancini Camillo , Vitali Roberta , Mancuso Mariateresa , McDowell Heather P. , Dominici Carlo , Raschellà Giuseppe
Published: November 2006

Purpose: Signaling through insulin-like growth factor I receptor (IGF-IR) is important for growth and survival of many tumor types. Neuroblastoma is sensitive to IGF.

Experimental Design: We assessed the ability of NVP-AEW541, a recently developed small molecule that selectively inhibits IGF-IR activity, for neuroblastoma growth effects in vitro and in vivo. Our data showed that, in a panel of 10 neuroblastoma cell lines positive for IGF-IR expression, NVP-AEW541 inhibited in vitro proliferation in a submicromolar/micromolar (0.4-6.8) range of concentrations.

Results: As expected, NVP-AEW541 inhibited IGF-II–mediated stimulation of IGF-IR and Akt. In addition to growth inhibition, the drug also induced apoptosis in vitro. Oral administration of NVP-AEW541 (50 mg/kg twice daily) inhibited tumor growth of neuroblastoma xenografts in nude mice. Analysis of tumors from the drug-treated animals revealed a marked apoptotic pattern and a decrease in microvascularization compared with controls. Interestingly, quantitative real-time PCR detected both in vitro and in vivo a significant down-regulation of mRNA for vascular endothelial growth factor (VEGF) caused by NVP-AEW541. In addition, in Matrigel-coated chambers and in severe combined immunodeficient mice tail vein injected with neuroblastoma cells, tumor invasiveness was significantly reduced by this agent. Analysis of IGF-IR expression in a series of 43 neuroblastoma primary tumors revealed IGF-IR positivity in 86% of cases.

Conclusions: Taken together, these data indicate that NVP-AEW541 can be considered as a novel promising candidate for treatment of neuroblastoma patients.
QW-1624F2-2, a synthetic analogue of 1,25-dihydroxyvitamin D3, enhances the response to other deltanoids and suppresses the invasiveness of human metastatic breast tumor cells
Authors: Sundaram Sujatha , Beckman Matthew J. , Bajwa Amandeep , Wei Jeffrey , Smith Kathleen M. , Posner Gary H. , Gewirtz David A.
Published: November 2006

The enzyme 24-hydroxylase, also known as CYP24, metabolizes 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and is an established marker of vitamin D activity. Our studies evaluated the influence of a low-calcemic 1,25(OH)2D3 analogue, QW-1624F2-2 (QW), on the regulation of CYP24 expression in MKL-4 cells, a metastatic mammary tumor cell model. 1,25(OH)2D3 and its analogue, EB 1089, stimulated CYP24 induction at both protein and transcript levels. In contrast, QW failed to produce a sustained stimulation of CYP24, due, in large part, to a reduction in the stability of the CYP24 message. QW enhanced the capacity of 1,25(OH)2D3 and EB 1089 to inhibit tumor cell proliferation by ∼2-fold. QW also blocked the sustained induction of CYP24 expression by 1,25(OH)2D3 and EB 1089, increased the potency of 1,25(OH)2D3 and EB 1089, and inhibited breast tumor cell proliferation and invasion. [Mol Cancer Ther 2006;5(11):2806–14]
Identification of SK3 channel as a new mediator of breast cancer cell migration
Authors: Potier Marie , Joulin Virginie , Roger Sébastien , Besson Pierre , Jourdan Marie-Lise , LeGuennec Jean-Yves , Bougnoux Philippe , Vandier Christophe
Published: November 2006

Potassium channels have been involved in epithelial tumorigenesis but the role of small-conductance Ca2+-activated K+ channels is unknown. We report here that small-conductance Ca2+-activated K+ channels are expressed in a highly metastasizing mammary cancer cell line, MDA-MB-435s. Patch-clamp recordings showed typical small-conductance Ca2+-activated K+ channel–mediated currents sensitive to apamin, 4-aminopyridine, and tetraethylammonium. Moreover, the cells displayed a high intracellular calcium concentration, which was decreased after 24 hours of apamin treatment. By regulating membrane potential and intracellular calcium concentration, these channels were involved in MDA-MB-435s cell migration, but not in proliferation. Only SK3 protein expression was observed in these cells in contrast to SK2, which was expressed both in cancer and noncancer cell lines. Whereas small interfering RNA directed against SK3 almost totally abolished MDA-MB-435s cell migration, transient expression of SK3 increased migration of the SK3-deficient cell lines, MCF-7 and 184A1. SK3 channel was solely expressed in tumor breast biopsies and not in nontumor breast tissues. Thus, SK3 protein channel seems to be a new mediator of breast cancer cell migration and represents a potential target for a new class of anticancer agents. [Mol Cancer Ther 2006;5(11):2946–53]
Inhibition of signal transducer and activator of transcription 3 activity results in down-regulation of Survivin following irradiation
Authors: Kim Kwang Woon , Mutter Robert W. , Cao Carolyn , Albert Jeffrey M. , Shinohara Eric T. , Sekhar Konjeti R. , Lu Bo
Published: November 2006

Signal transducer and activator of transcription 3 (Stat3) and Survivin are constitutively up-regulated in various human tumor cells. We previously found Survivin to be significantly reduced in response to radiation in human umbilical vein endothelial cells (HUVEC) but not in tumor cell lines. In this study, we examined the effect of Stat3 on Survivin expression in irradiated HUVECs and breast cancer cells. We also studied how inhibition of Stat3 and Survivin activity affects cell survival and angiogenesis following irradiation. We determined that Survivin was significantly increased by overexpression of an active Stat3 (Stat3-C). Following irradiation, the level of phospho-Stat3 Tyr705, but not phospho-Stat3 Ser727, was reduced in HUVECs, whereas it remained unchanged in irradiated breast cancer cells. Correspondingly, Stat3 DNA-binding activity following irradiation was specifically down-regulated in HUVECs but not in breast cancer cells. Mutation of Tyr705 abolished radiation-induced down-regulation of Survivin. Clonogenic and endothelial cell morphogenesis assays suggested that DN-Stat3 and DN-Survivin together resulted in the greatest radiosensitization of MDA-MB-231, decreasing angiogenesis and cell survival. In summary, Stat3 modulates Survivin, and both are potential therapeutic targets for radiation sensitization in breast cancer. [Mol Cancer Ther 2006;5(11):2659–65]
Isoginkgetin inhibits tumor cell invasion by regulating phosphatidylinositol 3-kinase/Akt–dependent matrix metalloproteinase-9 expression
Authors: Yoon Sang-Oh , Shin Sejeong , Lee Ho-Jae , Chun Hyo-Kon , Chung An-Sik
Published: November 2006

Matrix metalloproteinase (MMP)-9 plays a key role in tumor invasion. Inhibitors of MMP-9 were screened from Metasequoia glyptostroboides (Dawn redwood) and one potent inhibitor, isoginkgetin, a biflavonoid, was identified. Noncytotoxic levels of isoginkgetin decreased MMP-9 production profoundly, but up-regulated the level of tissue inhibitor of metalloproteinase (TIMP)-1, an inhibitor of MMP-9, in HT1080 human fibrosarcoma cells. The major mechanism of Ras-dependent MMP-9 production in HT1080 cells was phosphatidylinositol 3-kinase (PI3K)/Akt/nuclear factor-κB (NF-κB) activation. Expression of dominant-active H-Ras and p85 (a subunit of PI3K) increased MMP-9 activity, whereas dominant-negative forms of these molecules decreased the level of MMP-9. H-Ras did not increase MMP-9 in the presence of a PI3K inhibitor, LY294002, and a NF-κB inhibitor, SN50. Further studies showed that isoginkgetin regulated MMP-9 production via PI3K/Akt/NF-κB pathway, as evidenced by the findings that isoginkgetin inhibited activities of both Akt and NF-κB. PI3K/Akt is a well-known key pathway for cell invasion, and isoginkgetin inhibited HT1080 tumor cell invasion substantially. Isoginkgetin was also quite effective in inhibiting the activities of Akt and MMP-9 in MDA-MB-231 breast carcinomas and B16F10 melanoma. Moreover, isoginkgetin treatment resulted in marked decrease in invasion of these cells. In summary, PI3K/Akt is a major pathway for MMP-9 expression and isoginkgetin markedly decreased MMP-9 expression and invasion through inhibition of this pathway. This suggests that isoginkgetin could be a potential candidate as a therapeutic agent against tumor invasion. [Mol Cancer Ther 2006;5(11):2666–75]
C35 (C17orf37) is a novel tumor biomarker abundantly expressed in breast cancer
Authors: Evans Elizabeth E. , Henn Alicia D. , Jonason Alan , Paris Mark J. , Schiffhauer Linda M. , Borrello Melinda A. , Smith Ernest S. , Sahasrabudhe Deepak M. , Zauderer Maurice
Published: November 2006

Identification of shared tumor-specific targets is useful in developing broadly applicable therapies. In a study designed to identify genes up-regulated in breast cancer, a cDNA clone corresponding to a novel gene C35 (C17orf37) was selected by representational difference analysis of tumor and normal human mammary cell lines. Abundant expression of C35 transcript in tumors was confirmed by Northern blot and real-time PCR. The C35 gene is located on chromosome 17q12, 505 nucleotides from the 3′ end of the ERBB2 oncogene, the antigenic target for trastuzumab (HerceptinTM) therapy. The chromosomal arrangement of the genes encoding C35 and ERBB2 is tail to tail. An open reading frame encodes a 12-kDa protein of unknown function. Immunohistochemical analysis detected robust and frequent expression of C35 protein, including 32% of grade 1 and 66% of grades 2 and 3 infiltrating ductal carcinomas of the breast (in contrast to 20% overexpressing HER-2/neu), 38% of infiltrating lobular carcinoma (typically HER-2/neu negative), as well as tumors arising in other tissues. C35 was not detected in 38 different normal human tissues, except Leydig cells in the testes and trace levels in a small percentage of normal breast tissue samples. The distinct and favorable expression profile of C35 spanning early through late stages of disease, including high frequency of overexpression in various breast carcinoma, abundant expression in distant metastases, and either absence or low level expression in normal human tissues, warrants further investigation of the relevance of C35 as a biomarker and/or a target for development of broadly applicable cancer-specific therapies. [Mol Cancer Ther 2006;5(11):2919–30]
The legal background of the metaphor for forgiveness in Psalm ciii 12
Authors: Gregory Bradley C.
Published: November 2006

The use of the root rhq in legal idioms in ancient Near Eastern documents provides an illuminating background for understanding the metaphor for forgiveness in Ps. ciii 12.I am grateful to Gary A. Anderson for his comments and suggestions on this note.
Judeophobia in Context: Anti-Semitism among Modern Palestinians
Authors: Flores Alexander
Published: November 2006

The article is a critical assessment of the claim that anti-Semitic attitudes are widespread among modern Palestinians and that they are to a large extent the cause of their hostility towards Israel. In an overview of the development of the Palestine conflict, the contribution shows that this hostility can easily be explained by the nature of the conflict itself. In their perception of the conflict, Palestinians at times clearly distinguished between Zionism (or Israel) and Jews, but there also were instances of non-distinction which allowed for the spread of general enmity towards Jews. Before the Palestinians massively suffered from the results of the conflict and from the harm it caused, European-style anti-Semitism hardly existed among them. Further developments show a clear connection between the intensity of the conflict and the spread of anti-Semitic attitudes. Hence, reducing the scope of these attitudes appears to depend on political steps towards a settlement of the conflict and on an improved situation for the Palestinians.
'Going Bush': Black Magic, White Ambivalence and Boundaries of Belief in Postcolonial Kenya
Authors: McIntosh Janet
Published: November 2006

This article examines the ways in which contemporary white Kenyans know about, talk about and sometimes interact with what they call 'witchcraft' and 'magic' in ways they find deeply discomfiting. Although white Kenyans are at pains to justify their postcolonial advantages in Kenya in terms of a level-headed and pragmatic kind of personhood, many of them interact with indigenous religious ontologies more than ever, sometimes as manipulators of the occult and sometimes as its fear-stricken victims. Because of these contradictions between ideology and experience, white narratives about 'witchcraft' and 'magic' are frequently riddled with tensions and equivocations. Many white Kenyans find creative rhetorical strategies for dealing with these tensions, strategies that sometimes fly in the face of simple models of 'belief ' as a commitment to truth value by treating it as a state of vulnerability that can lay one open to mysterious ontological forces.
Jacobus Balduini: probably the author of the Summa feudorum Parmensis
Authors: Bezemer Kees
Published: November 2006

The MS Parma Biblioteca Palatina 1227 contains a feudal summa which in the MS is ascribed to Jacques de Revigny. Many scholars have, rightly, disputed this attribution, without indicating, however, the name of its true author. Jacobus Balduini is suggested to be the one. This attribution is partly based on a 'profile' made of the summa and its similarity to Balduini's Libellus instructionis advocatorum. It is argued that some elements of the summa may be the work of Benedictus de Isernia, a pupil of Balduini.
Member Diversity and Cohesion and Performance in Walking Groups
Authors: Shapcott Kim M. , Carron Albert V. , Burke Shauna M. , Bradshaw Michael H. , Estabrooks Paul A.
Published: November 2006

The purpose of the study was to examine the relationship of group member diversity in task-related attributes (i.e., self-efficacy, level of previous physical activity, and personal goals) and task-unrelated attributes (i.e., ethnicity and gender) to task cohesiveness and task performance in walking groups ( N varied from 1,324 to 1,392 groups for the analyses). For the task-related attributes, diversity in level of previous physical activity was significantly related to both task cohesion and group performance—as diversity increased, cohesion and performance decreased. For the task-unrelated attributes, diversity in gender was related to task cohesion—as diversity increased, cohesion decreased. Gender diversity was unrelated to group performance. The results are discussed in terms of their implications for the dynamics of task-oriented groups.
Geometrically caused image distortion effects and their influence on interpretation of EBSD measurements
Authors: Nolze G.
Published: November 2006

The imaging of high tilted flat sample surfaces in scanning electron microscopy has some special characteristics. A typical example is the trapezium distortion which is only detectable at low magnifications. In contrast to this, a rhomboidal distortion is discussed in the present paper which appears independent of the magnification used. Rhomboidal distortion is also caused by a simple geometrical misalignment, an additional slight tilt of the sample surface out of the plane of the microscope stage or the pretilted sample holder. The rhomboidal distortion may affect all image related orientation descriptions, e.g. also a texture characterisation. In order to draw attention to this unexpected influence, some typical examples are given and a simplified solution is proposed.
Microstructural development of α alumina scales developed on FeCrAl alloys
Authors: Prior D. J. , Al-Badairy H. , Seward G. G. E. , Veltkamp C. J. , Tatlock G. J.
Published: November 2006

A scanning electron microscope (SEM) study was conducted of α alumina scales developed on the surface of FeCrAl alloys during high temperature oxidation, using backscattered electron imaging, cathodoluminescence (CL) imaging, electron backscatter diffraction (EBSD) and X-ray microanalysis. CL variations relate to trace element distributions and to crystallographic orientations. The compositional variations suggest that grain boundary diffusion was dominant in the scale. The α alumina grains are equiaxed at the outer scale surface and columnar between here and the metal oxide interface; both grain types have a very strong crystallographic preferred orientation (CPO): a fibre texture of r axes perpendicular to the sheet. The CPO cannot be explained by substrate control or by plastic deformation. There is a correlation of the orientation of the anisotropic elastic properties of the scale and the likely thermal stress systems: one possible explanation is that the CPO may relate to oriented oxide nucleation during heating.
Treatment of Adult Acute Lymphoblastic Leukemia
Authors: Gökbuget Nicola , Hoelzer Dieter
Published: November 2006

In the early 1980s, adult acute lymphoblastic leukemia (ALL) was a rarely curable disease with overall survival < 10%. After adapting combinations employed by pediatric groups, the outcome improved to 30–40%. A period of stagnation followed with improvement only in distinct subgroups. In the past 5 years, however, striking new developments have been noticeable. Progress has been made in molecular diagnostics of ALL. Improvements to standard therapy including stem cell transplantation (SCT) have occurred and a variety of new drugs for ALL are under evaluation. Rapid diagnosis and classification of ALL is increasingly important to identify prognostic factors and molecular genetic subsets that will be the focus of “targeted” therapies as we enter the era of subset specific treatment. In the following review we will discuss treatment of adult ALL (excluding elderly patients,1 adolescents2 and patients with Ph/BCR-ABL positive ALL3).
Of Yeasts and Hyphae: A Hematologist’s Approach to Antifungal Therapy
Authors: Bow Eric J.
Published: November 2006

Improvements in anticancer treatments, the ability to modify myelosuppression profiles, greater duration and intensity of immunosuppression, and the variety of available antimicrobial therapies have influenced the spectrum of pathogens associated with invasive fungal infection complicating treatment of hematological malignancies and hematopoietic stem cell transplantation. The approaches to the management of these infections encompass strategies of prevention for all those at risk, pre-emptive therapy based upon surrogates of infection before the onset of clinical disease, empirical therapy for patients with clinical evidence of early disease, and directed or targeted therapy for infected patients with established disease. Chemoprophylaxis is effective if applied to the highest risk patients over the duration of the risk. Pre-emptive strategies, while promising, have yet to be validated and linked to reliably predictive nonmicrobiological diagnostic techniques. Empirical antifungal therapy, as it is currently applied, now seems questionable. Patients with probable or proven invasive fungal infection still have suboptimal outcomes despite the availability of promising anti-fungal agents. Strategies examining the concept of dose-intensity and combination regimens require careful study and cannot yet be regarded as an acceptable standard of practice.
Outcomes with Myeloid Malignancies
Authors: Scott Bart L. , Sandmaier Brenda M.
Published: November 2006

Reduced-intensity conditioning (RIC) regimens were initially introduced to provide allogeneic stem cell transplantation (HCT), a potentially curative procedure for myeloid malignancies, for patients who were not considered eligible for conventional myeloablative HCT either because of advanced age or excessive comorbidities. A variety of RIC regimens have been studied. The exact definition of RIC remains arbitrary and generally depends upon the perceived toxicity of a given regimen rather than the actual dose of chemotherapy or radiotherapy administered. In several published series, RIC regimens have demonstrated a reduction in non-relapse mortality (NRM), thereby accomplishing the initial goal of expanding the patient population eligible for this potentially curative procedure. Most retrospective studies performed to date have shown a decrease in NRM and an increase in relapse-related mortality with the use of RIC as opposed to conventional myeloablative HCT in myeloid malignancies. This appears to be particularly true for patients who are in relapse at the time of HCT. In contrast, patients who are in remission at time of HCT appear to have a reduction in NRM without a subsequent increase in relapse-related mortality. There is interest in applying RIC to younger patients and to patients with fewer comorbidities as they may have a reduction in NRM without a concomitant increase in relapse. Prospective multicenter studies are needed to define the optimal conditioning regimen, which is likely dependent upon a variety of disease-specific and patient-specific factors.
Pharmacogenetics-Based Coumarin Therapy
Authors: Gage Brian F.
Published: November 2006

To reduce the risk of hemorrhage, experts advocate prescribing the anticipated therapeutic dose to patients who are beginning coumarin therapy, but until now there was no accurate way to estimate that dose. Using pharmacogenetics-based coumarin therapy, clinicians can now estimate the therapeutic dose by genotyping their patients for single nucleotide polymorphisms (SNPs) that affect coumarin metabolism or sensitivity.

SNPs in the cytochrome P450 complex (CYP2C9) affect coumarin metabolism. Patients with either of two common variants, CYP2C9*2 or CYP2C9*3, metabolize coumarins slowly and are twice as likely to have a laboratory or clinical adverse event, unless their initial coumarin doses are reduced. SNPs in vitamin K epoxide reductase (VKORC1) correlate with coumarin sensitivity. Patients known to be homozygous for a common VKORC1 promoter polymorphism, −1639 G>A (also designated as VKOR 3673, haplotype A, or haplotype*2), should be started on lower coumarin doses than genotype GG patients. By providing an estimate of the therapeutic coumarin dose, pharmacogenetics-based therapy may improve the safety and effectiveness of coumarin therapy.
Effect of von Willebrand factor Y/C1584 on in vivo protein level and function and interaction with ABO blood group
Authors: Davies James Anthony , Collins Peter William , Hathaway Lee Sarah , Bowen Derrick John
Published: November 2006

Blood group O and the cysteine allele of the Y/C1584 change in von Willebrand factor (VWF) are enriched in type 1 VWD, but neither causes disease. We investigated the effect of C1584, alone and in combination with the ABO blood group, on the level and properties of plasma VWF. A cohort of 5052 blood donors was recruited: 50 donors were heterozygous for Y/C1584 and 5002 were homozygous for Y/Y1584. Mean VWF antigen (VWF:Ag) for heterozygotes (82 ± 35 IUdL−1) was significantly lower than for homozygotes (111 ± 37 IUdL−1) (P < .001). For each ABO blood group, VWF:Ag was decreased among Y/C1584 heterozygotes compared with Y/Y1584 homozygotes; a larger decrease was observed for group O. Among donors with VWF:Ag levels of 50 IUdL−1 or lower, Y/C1584 heterozygosity was markedly enriched (18%) compared with the entire cohort (1.5%). Blood group O was enriched to a lesser extent (2.4%), but Y/C1584 in conjunction with group O was strikingly enriched (34.8%). VWF collagen binding activity (VWF:CB) and ristocetin cofactor activity (VWF:RCo) were significantly lower for Y/C1584 heterozygotes than for Y/Y1584 homozygotes, and a qualitative difference in Y/C1584 plasma VWF multimer profile was observed compared with that for Y/Y1584 VWF. The data support a multifactorial basis for low VWF levels in some individuals.
Exploring glycopeptide-resistance in Staphylococcus aureus: a combined proteomics and transcriptomics approach for the identification of resistance-related markers
Authors: Scherl Alexander , François Patrice , Charbonnier Yvan , Deshusses Jacques M , Koessler Thibaud , Huyghe Antoine , Bento Manuela , Stahl-Zeng Jianru , Fischer Adrien , Masselot Alexandre , Vaezzadeh Alireza , Gallé Francesca , Renzoni Adriana , Vaudaux Pierre , Lew Daniel , Zimmermann-Ivol Catherine G , Binz Pierre-Alain , Sanchez Jean-Charles , Hochstrasser Denis F , Schrenzel Jacques
Published: November 2006

Background

To unravel molecular targets involved in glycopeptide resistance, three isogenic strains of Staphylococcus aureus with different susceptibility levels to vancomycin or teicoplanin were subjected to whole-genome microarray-based transcription and quantitative proteomic profiling. Quantitative proteomics performed on membrane extracts showed exquisite inter-experimental reproducibility permitting the identification and relative quantification of >30% of the predicted S. aureus proteome.

Results

In the absence of antibiotic selection pressure, comparison of stable resistant and susceptible strains revealed 94 differentially expressed genes and 178 proteins. As expected, only partial correlation was obtained between transcriptomic and proteomic results during stationary-phase. Application of massively parallel methods identified one third of the complete proteome, a majority of which was only predicted based on genome sequencing, but never identified to date. Several over-expressed genes represent previously reported targets, while series of genes and proteins possibly involved in the glycopeptide resistance mechanism were discovered here, including regulators, global regulator attenuator, hyper-mutability factor or hypothetical proteins. Gene expression of these markers was confirmed in a collection of genetically unrelated strains showing altered susceptibility to glycopeptides.

Conclusion

Our proteome and transcriptome analyses have been performed during stationary-phase of growth on isogenic strains showing susceptibility or intermediate level of resistance against glycopeptides. Altered susceptibility had emerged spontaneously after infection with a sensitive parental strain, thus not selected in vitro. This combined analysis allows the identification of hundreds of proteins considered, so far as hypothetical protein. In addition, this study provides not only a global picture of transcription and expression adaptations during a complex antibiotic resistance mechanism but also unravels potential drug targets or markers that are constitutively expressed by resistant strains regardless of their genetic background, amenable to be used as diagnostic targets.
Preliminary results of phase I trial of oral uracil/tegafur (UFT), leucovorin plus irinotecan and radiation therapy for patients with locally recurrent rectal cancer
Authors: Yasui Masayoshi , Ikeda Masataka , Sekimoto Mitsugu , Yamamoto Hirofumi , Takemasa Ichiro , Ueda Takafumi , Shimizu Junzo , Fukunaga Mutsumi , Suzuki Osamu , Inoue Takehiro , Monden Morito
Published: November 2006

Background

Surgical attempts for locally recurrent rectal cancer often fail due to local re-recurrence and distant metastasis. Preoperative chemoradiation may enhance better local control and survival. The aim of this study was to assess the safety of oral uracil and tegafur (UFT) plus leucovorin (LV), and irinotecan combined with radiation and determine the maximum-tolerated dose (MTD) and dose limiting toxicity (DLT) of the triple drug regimen.

Patients and methods

Patients with locally recurrent rectal cancer received escalating doses of irinotecan on days 1, 8, 15, and 22 (starting at 30 mg/m2, with 10 mg increments between consecutive cohorts) and fixed doses of UFT (300 mg/m2) plus LV (75 mg/day) on days 3 to 7, 10 to 14, 17 to 21, and 24 to 28. Radiation was given 5 days per week totaling 40 to 50 Gy (2Gy/day).

Results

Six patients were treated at the starting dose, and 2 received the full scheduled chemoradiotherapy. The other 4 patients had grade 3 diarrhea and diarrhea was the DLT. One patient had partial response and he had subsequently radical surgical resection. Median progression free survival for local recurrence was 320 days.

Conclusion

Irinotecan plus UFT/LV with concomitant radiotherapy in patients with locally recurrent rectal cancer was not feasible due to diarrhea in this setting. Modification of the treatment is needed.
Augmentation of Heat Transfer on the Downward Surface of a Heated Plate by Ion Injection
Authors: GRASSI WALTER , TESTI DANIELE , VISTA DAVIDE DELLA , TORELLI GABRIELE
Published: November 2006

Abstract:  The heat transfer characteristics of an electrohydrodynamically induced submerged impinging liquid flow are studied in a point‐plane configuration. The working fluid, HFE‐7100, is a weakly polar dielectric. Thermofluid‐dynamic conditions as close as possible to the microgravity ones are obtained by heating a confined, downward‐facing plate. Heat transfer coefficients on the plate can be stably enhanced by over 10 times, with negligible additional work, by means of the ion injection technique.
Numerical Computation on Magnetothermal Air Jet in Gravitational and Nongravitational Fields
Authors: AKAMATSU MASATO , HIGANO MITSUO , OGASAWARA HITOSHI
Published: November 2006

Abstract:  Two‐dimensional numerical computations were carried out in order to elucidate the effect of a Kelvin force on the air in two coaxial circular pipes with open ends under both gravitational and nongravitational fields. The outer pipe with open ends corresponds to the bore space of the superconducting magnet. The inner pipe with open ends is assumed to be placed inside this bore space. The sidewall of the outer pipe is cooled isothermally. The central region of the inner pipe is heated isothermally and the other region is thermally insulated. The magnetic gradient that was produced by the electric current circulating within the circular electric coil was applied to air in two coaxial circular pipes with a thermal gradient. Moreover, the present numerical computations were carried out by changing the relative positions of the circular electric coil and the inner pipe. In both gravitational and nongravitational fields, when the circular electric coil was placed at the end of the heated region of the inner pipe, the Kelvin force was produced in the inner pipe and the magnetothermal air jet was created. As a result, the hotter air rapidly flowed out from the end of the inner pipe. These phenomena could be successfully explained by considering the temperature dependence of the mass magnetic susceptibility of air according to Curie's law.
Noncontact Thermophysical Property Measurement by Levitation of a Thin Liquid Disk
Authors: LEE SUNGHO , OHSAKA KENICHI , REDNIKOV ALEXEI , SADHAL SATWINDAR SINGH
Published: November 2006

Abstract:  The purpose of the current research program is to develop techniques for noncontact measurement of thermophysical properties of highly viscous liquids. The application would be for undercooled liquids that remain liquid even below the freezing point when suspended without a container. The approach being used here consists of carrying out thermocapillary flow and temperature measurements in a horizontally levitated, laser‐heated thin glycerin disk. In a levitated state, the disk is flattened by an intense acoustic field. Such a disk has the advantage of a relatively low gravitational potential over the thickness, thus mitigating the buoyancy effects, and helping isolate the thermocapillary‐driven flows. For the purpose of predicting the thermal properties from these measurements, it is necessary to develop a theoretical model of the thermal processes. Such a model has been developed, and, on the basis of the observed shape, the thickness is taken to be a minimum at the center with a gentle parabolic profile at both the top and the bottom surfaces. This minimum thickness is much smaller than the radius of disk drop and the ratio of thickness to radius becomes much less than unity. It is heated by laser beam in normal direction to the edge.
A general three‐dimensional momentum equation is transformed into a two‐variable vorticity equation. For the highly viscous liquid, a few millimeters in size, Stokes equations adequately describe the flow. Additional approximations are made by considering average flow properties over the disk thickness in a manner similar to lubrication theory. In the same way, the three‐dimensional energy equation is averaged over the disk thickness. With convection boundary condition at the surfaces, we integrate a general three‐dimensional energy equation to get an averaged two‐dimensional energy equation that has convection terms, conduction terms, and additional source terms corresponding to a Biot number. A finite‐difference numerical approach is used to solve these steady‐state governing equations in the cylindrical coordinate system. The calculations yield the temperature distribution and the thermally driven flow field. These results have been used to formulate a model that, in conjunction with experiments, has enabled the development of a method for the noncontact thermophysical property measurement of liquids.
Ionizing Radiation and Cardiovascular Disease
Authors: HOEL DAVID G.
Published: November 2006

Abstract:  For more than 15 years the A‐bomb survivor studies have shown increased noncancer mortality due to radiation exposures. The most prominent cause of this increase is circulatory disease mortality. Although the estimated relative risk is less than for solid cancers (1.2 versus 1.6 per Sv), there are measurable increases in cardiovascular disease mortality at doses greater than 0.5 Sv. The evidence for circulatory diseases in mortality studies of occupational cohorts exposed to external radiation is less compelling. It is generally accepted that atherosclerosis is an inflammatory disease of the arteries and a risk factor for myocardial infarction. Immunological markers for inflammatory disease have been shown to be dose related in A‐bomb survivors. Evidence from animal studies reveals increased cardiovascular mortality and arterial endothelial damage from both neutron and, to a lesser extent, gamma exposures.
Applying Cost Analyses to Drive Policy That Protects Children
Authors: TRASANDE LEONARDO , SCHECHTER CLYDE , HAYNES KARLA A. , LANDRIGAN PHILIP J.
Published: November 2006

Abstract:  Exposure in prenatal life to methylmercury (MeHg) has become the topic of intense debate in the United States after the Environmental Protection Agency (EPA) announced a proposal in 2004 to reverse strict controls on emissions of mercury from coal‐fired power plants that had been in effect for the preceding 15 years. This proposal failed to incorporate any consideration of the health impacts on children that would result from increased mercury emissions. We assessed the impact on children's health of industrial mercury emissions and found that between 316,588 and 637,233 babies are born with mercury‐related losses of cognitive function ranging from 0.2 to 5.13 points. We calculated that decreased economic productivity resulting from diminished intelligence over a lifetime results in an aggregate economic cost in each annual birth cohort of $8.7 billion annually (range: $0.7–$13.9 billion, 2000 dollars). $1.3 billion (range: $51 million–$2.0 billion) of this cost is attributable to mercury emitted from American coal‐fired power plants. Downward shifts in intellectual quotient (IQ) are also associated with 1566 (range: 115–2675) excess cases of mental retardation (MR defined as IQ < 70) annually. This number accounts for 3.2% (range: 0.2–5.4%) of MR cases in the United States. If the lifetime excess cost of a case of MR (excluding individual productivity losses) is $1,248,648 in 2000 dollars, then the cost of these excess cases of MR is $2.0 billion annually (range: $143 million–$3.3 billion). Preliminary data suggest that more stringent mercury policy options would prevent thousands of cases of MR and billions of dollars over the next 25 years.
Worldwide Governmental Efforts to Locate and Destroy Chemical Weapons and Weapons Materials
Authors: TRAPP RALF
Published: November 2006

Abstract:  The article gives an overview on worldwide efforts to eliminate chemical weapons and facilities for their production in the context of the implementation of the 1997 Chemical Weapons Convention (CWC). It highlights the objectives of the Organisation for the Prohibition of Chemical Weapons (OPCW), the
international agency set up in The Hague to implement the CWC, and provides an overview of the present status of implementation of the CWC requirements with respect to chemical weapons (CW) destruction under strict international verification. It addresses new requirements that result from an increased threat that terrorists might attempt to acquire or manufacture CW or related materials.
The article provides an overview of risks associated with CW and their elimination, from storage or recovery to destruction. It differentiates between CW in stockpile and old/abandoned CW, and gives an overview on the factors and key processes that risk assessment, management, and communication need to address. This discussion is set in the overall context of the CWC that requires the completion of the destruction of all declared CW stockpiles by 2012 at the latest.