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J Oncol. 2010; 2010: 351908.=20
Published online 2010 = April 18.=20 doi:=20 10.1155/2010/351908.
PMCID:=20 = PMC2857608
Copyright=20 =C2=A9 2010 Shingo Takano et al.
Molecular Therapeutic Targets for Glioma=20 Angiogenesis
Shingo=20 Takano,1* Toshiharu Yamashita,2 = and Osamu=20 Ohneda2
1Department of Neurosurgery, = Institute of=20 Clinical Medicine, University of Tsukuba, Tsukuba Ibaraki = 305-8575,=20 Japan
2Regenerative Medicine/Stem Cell = Biology,=20 Institute of Basic Medical Science, University of Tsukuba, Tsukuba = Ibaraki=20 305-8575, Japan
*Shingo Takano: Email:=20 shingo4/at/md.tsukuba.ac.jp
Academic Editor: = Arkadiusz=20 Dudek
Received October 28, 2009; Revised = December 9, 2009;=20 Accepted January 27, 2010.
This is an open access article = distributed under=20 the Creative Commons Attribution License, which permits = unrestricted use,=20 distribution, and reproduction in any medium, provided the = original work=20 is properly cited.
Abstract
Due to the = prominent=20 angiogenesis that occurs in malignant glioma, antiangiogenic = therapy has=20 been attempted. There have been several molecular targets that are = specific to malignant gliomas, as well as more broadly in systemic = cancers. In this review, I will focus on some topics related to = molecular=20 therapeutic targets for glioma angiogenesis. First, important = angiogenic=20 factors that could be considered molecular targets are VEGF, = VEGF-induced=20 proteins on endothelial cells, tissue factor, osteopontin,=20 =CE=B1v=CE=B23 integrin, = and thymidine=20 phosphorylase as well as endogenous inhibitors, soluble Flt1, and=20 thrombospondin 1. Second, hypoxic areas are also decreased by = metronomic=20 CPT11 treatment as well as temozolomide. Third, glioma-derived = endothelial=20 cells that are genetically and functionally distinct from normal=20 endothelial cells should be targeted, for example, with SDF-1 and = CXCR7=20 chemokine. Fourth, endothelial progenitor cells (EPCs) likely = contribute=20 towards glioma angiogenesis in the brain and could be useful as a = drug=20 delivery tool. Finally, blockade of delta-like 4 (Dll4) results in = a=20 nonfunctioning vasculature and could be another important target = distinct=20 from VEGF.
Malignant gliomas = tend to be=20 highly vascularized and contain hypoxic regions. Therefore, an=20 antiangiogenic strategy is promising for malignant gliomas [1, 2]. In this review, I focus on some molecular = therapeutic=20 targets for glioma angiogenesis: (1) angiogenic factors, (2) = hypoxia, (3)=20 glioma-derived endothelial cells, and (4) resistance to = antiangiogenic=20 therapy. The problem of how to treat patients who fail to respond = to=20 antiangiogenic therapy remains a challenge, and the mechanisms of=20 resistance are being studied. The potential mechanisms by which = tumor=20 cells can evade antiangiogenic therapy include upregulation of=20 non-VEGF-mediated pathways of angiogenesis, recruitment of bone=20 marrow-derived cells, increased pericyte coverage, and increased = use of=20 preexistent vasculature by invasion [3].
Vascular endothelial = growth factor=20 (VEGF) is a major angiogenic factor in glioblastoma [4]. VEGF is localized within tumor cytoplasm and = endothelium=20 (Figure 13D"Figure).=20 VEGF is predominantly located in the perinecrotic area, which is = referred=20 to as the pseudopallisading area and appears to be hypoxic. By = contrast,=20 there are few VEGF positive cells in low-grade astrocytomas and no = VEGF=20 positive cells in the normal brain. We initially demonstrated = increased=20 expression of VEGF in malignant glioma tissues, with both ELISA = (Figure 23D"Figure)=20 and immunohistochemistry. We also demonstrated high VEGF protein=20 concentrations in the cyst fluid from glioma, but VEGF was not = detectable=20 in the serum.
3D"Figure
Figure=20 1
VEGF = localization=20 in gliomas. (a)=E2=80=93(c) Glioblastoma. VEGF localizes in = the cytoplasm of=20 the tumor cells and tumor capillary around the necrosis and = the=20 tumor periphery. (d) Anaplastic astroctytoma. (e) Diffuse=20 astrocytoma. (f) Normal brain.=20 (more ...)
VEGF-related angiogenic factors = have been also=20 clearly demonstrated in glioma tissues by RT-PCR and = immunohistochemistry.=20 Tissue factor is highly expressed in malignant gliomas associated = with=20 VEGF expression (Figure 33D"Figure)=20 [5]. Also, osteopontin and=20 =CE=B1v=CE=B23 integrin, = which are also=20 induced by VEGF in endothelium, are predominantly expressed in = tumor=20 endothelium. Another angiogenic factor, thymidine phosphorylase, = is also=20 only expressed in malignant gliomas, but not in low-grade glioma = or normal=20 brain (Figure 43D"Figure)=20 [6].
3D"Figure
Figure=20 2
VEGF = concentration=20 in the various brain tumors.
3D"Figure
Figure=20 3
Tissue = factor and=20 VEGF mRNA expression in human glioma samples. Tissue factor=20 expression was frequent and highly observed in glioblastomas = associating with VEGF expression.
Endogenous angiogenesis inhibitors = are=20 important molecules in the delicate balance of angiogenic = potential in=20 tumors. The soluble form of the VEGF receptor 1 (sFlt-1) is a = measurable,=20 potent, and specific VEGF inhibitor. The concentrations of sFlt-1 = and VEGF=20 have been measured in glioma tissues by ELISA. A VEGF/sFlt-1 ratio = greater=20 than 1 is a worse prognostic factor in glioblastomas (Figure 53D"Figure)=20 [7]. The significance of the VEGF/sFlt-1 ratio as a = prognostic=20 factor is greater than for the VEGF concentration alone, = suggesting that=20 the angiogenic balance between angiogenic factor and its inhibitor = is=20 important in tumor angiogenesis. Experimentally, transfection of = human=20 glioma cells with sFlt-1 demonstrated low expression of VEGF mRNA = compared=20 to transfection with an empty vector. The tumor growth of these = sFlt-1=20 transfectants was inhibited, but the inhibitory activity was = limited [7]. Another endogenous angiogenic inhibitor, = thrombospondin1=20 (TSP1), was introduced into human U87 glioma cells by transfection = (Figure 63D"Figure).=20 The glioma growth of the TSP1 transfectant was significantly = inhibited=20 compared to those of parent and vector-alone transfectants (Figure 73D"Figure)=20 [7]. These clinical and experimental data support = the=20 importance of angiogenic balance as a key factor in antiangiogenic = therapy. This is likely because these endogenous angiogenesis = inhibitors=20 are upregulated in malignant gliomas, as a consequence of the = upregulation=20 of angiogenic factors.
3D"Figure
Figure=20 4
Thymidine = phosphorylase immunohistochemistry in human gliomas. = Glioblastoma=20 shows intense immunoreaction for thymidine phosphorylase = both in=20 tumor and endothelial cells (a). Diffuse astrocytoma shows = no=20 expression (b). Some of the tymidine phosphorylase=20 (more ...)
3D"Figure
Figure=20 5
Malignant = glioma=20 survival by VEGF/sFlt-1 ratio.
3D"Figure
Figure=20 6
Characterization of=20 thrombospondin-1 transfected U87. Thrombospondin-1 = expression was=20 markedly elevated in the transfectant (TSP) compared to = vector alone=20 (Neo) and parent U87 (P). Also VEGF expression was decreased = in=20 transfectant (TSP).
The general growth factor receptor = inhibitor,=20 suramin, was investigated for its antiangiogenic action [8]. Suramin inhibited physiologic angiogenesis in a = dose-dependent manner, based on the chorioallantoic membrane (CAM) = assay=20 (= Table 1). Suramin = inhibited=20 the bFGF-induced endothelial expression of urokinase-type=20 plasminogen-activator (uPA) using gelatin zymogram (Figure 83D"Figure).=20 uPA is closely related to the initiating step of angiogenesis, = degradation=20 of the extracellular matrix. Using a rat intracranial C6 glioma = model,=20 suramin inhibited Ki67 labeling of the tumor endothelium (Figure 93D"Figure)=20 [9]. All of these data suggest that suramin can = inhibit=20 physiological and tumor angiogenesis at multiple levels.
3D"Figure
Figure=20 7
Inhibition of=20 glioma growth by thrombospondin-1 transfection. The glioma = growth is=20 significantly inhibited by thrombospondin-1 transfectant = (TSP-1=20 transfectant) compared to parent U87 and vector alone=20 (Neotransfectant).
=
3D"Table<= /DIV>
= Table=20 1
Inhibition of=20 angiogenesis in the chick chorioallantoic membrane=20 assay.
3D"Figure
Figure=20 8
Suramin = inhibition=20 of bFGF induced endothelial cell urokinase type plasminogen=20 activator activity on gelatin zymogram.
Recently, the anti-VEGF = antibody,=20 bavacizumab, has been used in the treatment of glioblastoma [10]. The growth inhibitory effect is dramatic, = especially=20 when determined with MRI enhancement and MRI perfusion study [11]. Interestingly, ACNU=20 = (1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-cholroethyl)-3-nitrosoure= a=20 hydrochloride) chemotherapeutic agents resulted in upregulation of = VEGF=20 mRNA in glioma cells (Figure 103D"Figure)=20 [12]. A similar effect on upregulation of VEGF has = been=20 demonstrated by irradiation of glioma cells. Thus, the combination = of VEGF=20 antagonism, that is, VEGF antibody in the initial glioma therapy, = is a=20 reasonable strategy in ACNU chemotherapy and in radiation therapy = (Figure 113D"Figure).=20 The VEGF antibody is attractive for attacking tumor stem cells, as = a new=20 strategy to combat glioblastomas, because the VEGF antibody could = inhibit=20 maintenance of glioma stem cells by destroying glioma vascular = niche [13, 14], in contrast to the effects of radiation or = other=20 chemotherapeutics. However, the antiangiogenic antiglioma effect = is=20 transient (Figure 123D"Figure3D"Figure).=20 Congruent with the results obtained in orthotropic mouse models of = GBM,=20 four recent clinical studies have implicated proinvasive = adaptation in=20 humans, as observed by MRI, in a subset of GBM patients who = developed=20 multifocal or diffuse recurrence of the tumor during a course of = anti-VEGF=20 therapy with bevacizumab, as in our case [15=E2=80=9317]. Thus, there is a clear need for alternative = strategies=20 after bevacizumab failure.
3D"Figure
Figure=20 9
Suramin = inhibition=20 of tumor endothelial cell Ki67 labeling.
3D"Figure
Figure=20 10
Elevation = of VEGF=20 mRNA expression by ACNU treatment, but not etoposide and = CDDP=20 treatment, in human glioma cells (U87 and = U251).
3D"Figure
Figure=20 11
Glioma = growth=20 inhibition by VEGF antibody, ACNU, and the combination of = both=20 treatments with U87 subcutaneous (a) and intracranial (b)=20 model.
One of the = mechanisms of=20 resistance to angiogenic treatment is the presence of hypoxic = regions in=20 glioma tissues. Hypoxia-inducible factor 1=CE=B1 = (HIF1=CE=B1) is=20 induced by hypoxia and is upstream of VEGF mRNA expression.=20 Immunohistochemical expression of HIF-1=CE=B1 clearly = correlated with=20 the degree of glioma malignancies and predicted survival among = patients=20 with malignant gliomas (Figure 133D"Figure)=20 and the degree of necrosis on MRI (data not shown). Therefore,=20 HIF-1=CE=B1 has been the focus of antiangiogenic = treatment [18]. Downregulation of HIF-1=CE=B1 in = glioma cells using=20 siRNA resulted in growth inhibition and an angiosuppressive effect = on=20 glioma growth (unpublished data). Metronomic chemotherapy is a = promising=20 strategy to overcome resistance to antiangiogenic treatment [19]. We demonstrated that SN38, the active = metabolite of=20 CPT11, exhibited an antiangiogenic effect (Figure 143D"Figure).=20 SN38 inhibited HIF-1=CE=B1 and VEGF mRNA and protein = expression of=20 glioma cells in a dose- and time-dependent manner [20]. Metronomic CPT11 treatment of gliomas = exhibited growth=20 inhibitory effects without systemic toxicity, that is, through = comparison=20 of body weight loss that was not observed by conventional CPT11 = treatment.=20 Tumor tissues treated with metronomic CPT11 exhibited decreased = expression=20 of HIF-1=CE=B1 protein and pimonidazole expression, which = were=20 indicative of areas of hypoxia by immunohistochemistry (Figure 153D"Figure).=20 A recent advance in glioma chemotherapy is the discovery of = temozolomide.=20 Temozolomide is a powerful chemotherapeutic agent that prolongs = overall=20 survival of initial glioblastoma by up to 2.5 months [21]. More recently, the feasibility of bevacizumab = with=20 radiation therapy and temozolomide in newly diagnosed high-grade = gliomas=20 has been reported [22, 23]. Interestingly, temozolomide has an inhibitory = effect on=20 HIF-1=CE=B1 expression and endothelial cell tube = formation [24]. The metronomic temozolomide treatment is = reasonable and=20 clinical results have been demonstrated [25, 26].
3D"Figure3D"Figure
Figure=20 12
Clinical = course of=20 a case with recurrent malignant glioma with bevacizumab and = CPT11=20 treatment. After 3 cycles enhanced tumor and perifocal edema = is=20 markedly diminished (Bev 23D"m).=20 However, after 6 cycles T2 high intense tumors regrow with=20 minimal=20 (more ...)
3D"Figure
Figure=20 13
Malignant = glioma=20 survival with hypoxia inducible factor 1=CE=B1 = (HIF-1=CE=B1)=20 expression on immunohistochemistry. HIF-1=CE=B1 = expression is a=20 negative prognostic factor.
3D"Figure
Figure=20 14
Antiangiogenic=20 effect of SN38, active metabolite of CPT11. Low dose of SN38 = (0.01=20 and 0.13D"=CE=BCM) inhibited=20 tube formation of HUVEC.
Many studies = focusing on tumor=20 angiogenesis and endothelial biology are based on established = normal cells=20 lines that is, human umbilical vein endothelial cells (HUVECs). = Whether or=20 not tumor endothelial cells and normal endothelial cells are = genetically=20 and functionally identical remains controversial. Comparisons = between=20 tumor-derived and normal ECs have been made for a variety of = systemic=20 tumors [27]. They have shown that tumor endothelium = exhibits a=20 phenotype of activated ECs, as reflected in the high expression of = angiogenic molecules, that is, VEGFR, the angiopoietin receptor = Tie2, and=20 the adhesion molecules ICAM-1, E-selectin, and CD44. In recent=20 publications, researchers have suggested that the tumor-associated = ECs=20 derived from GBM tissues have different phenotypic and functional=20 properties compared to normal ECs [28, 29]; these differences may result in less = effective=20 antiangiogenic therapy if the target molecules are only expressed = in=20 normal blood vessels. Moreover, these publications have not = mentioned the=20 potential for interactions between tumor cells and tumor-derived=20 endothelial cells. We isolated tumor endothelial cells from human=20 glioblastoma samples using flow cytometry, cultured them, and = analyzed the=20 genetic differences between these cell types and HUVEC regarding = the mRNA=20 and protein expression of angiogenic factors and chemokines.=20 Glioblastoma-derived endothelial cells (GBMECs) exhibited high = expression=20 of VEGF, SDF-1, and CXCR7 mRNA compared to HUVEC, and GBMECs = exhibited no=20 expression of CXCR4 mRNA (Figure 163D"Figure,=20 unpublished data). We are now investigating functional differences = between=20 GBMECs and HEUVEC as well as the interaction between GBMECs and = glioma=20 cells using a coculture system. To obtain successful results with=20 antiangiogenic therapy, tumor endothelial cells should be targeted = in the=20 future.
3D"Figure
Figure=20 15
Hypoxia = inducible=20 factor 1=CE=B1 expression and hypoxic area with (b, = d) and=20 without (a, c) metronomic CPT11 treatment. = HIF-1=CE=B1=20 expression and hypoxic area around the necrosis of glioma = tissue=20 decreased with treatment.
Another important = mechanism of=20 resistance to antiangiogenic treatment is related to EPCs. EPCs = are=20 introduced into tumor angiogenesis by tumor stimuli from the bone = marrow.=20 We investigated the role of EPCs on glioma angiogenesis. C6 glioma = cells=20 (5 =C3=97 106 cells) were stereotactically implanted = into the brain.=20 After 7 days, EPCs (3 =C3=97 105 cells) that were = harvested from=20 umbilical cord blood [30] were intravenously injected via the tail vein. = Seven=20 days after the EPC injection, the rats were sacrificed and the C6 = gliomas=20 in the brain were fixed and stained with CD31. EPC-injected C6 = glioma=20 demonstrated a large narrow vascular network. The vessel length is = significantly longer than EPCs in an uninjected tumor (Figure 173D"Figure).=20 Fluoroscopy demonstrated that GFP-labeled EPCs localized along = with=20 lectin-labeled tumor vessels (Figure 183D"Figure).=20 This result suggests that EPC could induce homing to the glioma=20 vasculature and that this characteristic of tumor vasculature = homing is=20 useful when considering EPCs as drug delivery tools. If the EPCs = contain=20 angiogenesis inhibitors, the angiogenesis inhibitor is = automatically=20 delivered to the tumor vasculature. To date, this new strategy has = not=20 been published.
3D"Figure
Figure=20 16
Angiogenic factor=20 and chemokine expression in HUVEC and glioblastoma derived=20 endothelial cells (GBMECs). GBMECs show high expression of = VEGF,=20 SDF-1, and CXCR7 compared to HUVEC and no expression of=20 CXCR4.
3D"Figure
Figure=20 17
Rich = vascular=20 network with EPC-injected glioma. The vessel length of = EPC-injected=20 tumor (a) is significantly longer than those of control=20 (b).
Finally, the question = remains, what=20 are the current possible target molecules for glioma angiogenesis? = Norden=20 et al. [31] reported some molecules other than VEGF. Among = them,=20 delta-like 4 (Dll4) remains promising, because the mechanisms of=20 angiosuppression are quite different to those of VEGF and the role = of Dll4=20 is reciprocal to VEGF [32, 33]. Remarkably, Dll4 and VEGF are the only known = genes for=20 which loss of a single allele results in embryonic lethality due = to=20 failure to form a functional vasculature. Dll4 is exclusively = expressed by=20 endothelial cells; therefore, this ligand is a potential = therapeutic=20 target. Although blocking Dll4 appears to promote angiogenesis, = the=20 neovasculature is functionally abnormal and it cannot support = tumor cell=20 survival [34]. Preclinical studies have shown that blockade = of Dll4=20 was effective in inhibiting the growth of tumors that are = resistant to=20 VEGF inhibition [32]. Whereas most of current antiangiogenesis = approaches act=20 through the reduction or elimination of tumor blood vessels, Dll4 = blockade=20 results in the formation of a nonfunctional vasculature that is = unable to=20 support tumor growth. This paradoxical strategy for targeting = tumors will=20 be the focus of intense research for years ahead.
Furthermore, the = expression of=20 recombinant toxic proteins that specifically target tumor = endothelium=20 appears to be promising [35]. Fusion proteins directed against = urokinase-type=20 plasminogen-activator receptor (uPAR) may be appropriate for = targeting=20 endothelial cells in the tumor vasculature compared with normal=20 endothelium, as uPAR may be preferentially expressed in = proliferating=20 endothelium. The efficacy of protein DTAT13 that was synthesized = to target=20 uPAR on the neovasculature and uPAR- and interleukin-13-expressing = glioblastoma cells has been demonstrated on glioma growth in vitro = and in=20 vivo [36].
7. Conclusion
Anti-angiogenesis = therapy for=20 malignant gliomas is promising by not only inhibiting angiogenesis = but=20 also through alteration of the tumor microenvironment, that is, = the tumor=20 vascular niche. Moreover, various combinations of strategies = including the=20 development of new molecular targets have been investigated. = Overcoming=20 resistance to antiangiogenic therapy with minimal side effects = should be=20 considered.
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Articles from Journal of=20 Oncology are provided here courtesy of
Hindawi Publishing=20 Corporation
3D"Figure
Figure=20 18
EPC = homing to=20 glioma vasculature. 11 days after injection of GFP labeled = EPCs,=20 EPCs localize lectin labeled glioma = vasculature.

PubMed articles by these = authors

  • Takano,=20 S.
  • Yamashita,=20 T.
  • Ohneda,=20 O.

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  • ReviewNovel anti-angiogenic therapies = for=20 malignant gliomas.=20

    Lancet Neurol. 2008 Dec; = 7(12):1152-60.=20

    [Lancet Neurol. 2008]

  • ReviewAntiangiogenic therapy in = malignant=20 glioma: promise and challenge.=20

    Curr Pharm Des. 2007; = 13(35):3545-58.=20

    [Curr Pharm Des. 2007]

  • Tissue=20 factor, osteopontin, alphavbeta3 integrin expression in = microvasculature=20 of gliomas associated with vascular endothelial growth factor=20 expression.=20

    Br J Cancer. 2000 Jun; = 82(12):1967-73.=20

    [Br J Cancer. 2000]

  • Combination=20 of stromal-derived factor-1alpha and vascular endothelial growth = factor=20 gene-modified endothelial progenitor cells is more effective for = ischemic neovascularization.=20

    J Vasc Surg. 2009 Sep; = 50(3):608-16. Epub=20 2009 Jul 12.

    [J Vasc Surg. 2009]

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"300px" : "200px"); = PADDING-TOP: 0.25em; BORDER-BOTTOM: transparent 1px solid; TOP: 1.4em; = _top: 1.6em } UL.noext-menu LI UL.opened LI { MARGIN-BOTTOM: 3px } UL.noext-menu LI UL.opened LI.active-item { PADDING-RIGHT: 0px; PADDING-LEFT: 0px; PADDING-BOTTOM: 0px; = PADDING-TOP: 0px; BACKGROUND-COLOR: #aaaaaa } UL.opened LI.active-item A { COLOR: #ffffff } UL.noext-menu LI UL A { PADDING-RIGHT: 0px; PADDING-LEFT: 0px; PADDING-BOTTOM: 2px; MARGIN: 0px = 3px; COLOR: #222222; PADDING-TOP: 2px; TEXT-DECORATION: none } .noext-menu-hidden { COLOR: transparent! important; BACKGROUND-COLOR: transparent! important } .noext-menu-hidden A.first-link { COLOR: transparent! important; BACKGROUND-COLOR: transparent! important } ------=_NextPart_000_0000_01CAECAE.BD89CDB0 Content-Type: text/css; charset="iso-8859-1" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.ncbi.nlm.nih.gov/core/extjs/ext-2.2/resources/css/panel.css .x-panel { BORDER-RIGHT: #99bbe8 0px solid; BORDER-TOP: #99bbe8 0px solid; = BORDER-LEFT: #99bbe8 0px solid; BORDER-BOTTOM: #99bbe8 0px solid } .x-panel-header { BORDER-RIGHT: #99bbe8 1px solid; PADDING-RIGHT: 3px; BORDER-TOP: = #99bbe8 1px solid; PADDING-LEFT: 5px; BACKGROUND: = url(../images/default/panel/white-top-bottom.gif) repeat-x 0px -1px; = PADDING-BOTTOM: 4px; FONT: bold 11px/15px = tahoma,arial,verdana,sans-serif; OVERFLOW: hidden; BORDER-LEFT: #99bbe8 = 1px solid; COLOR: #15428b; PADDING-TOP: 5px; BORDER-BOTTOM: #99bbe8 1px = solid; ZOOM: 1 } .x-panel-body { BORDER-RIGHT: #99bbe8 1px solid; BORDER-TOP: #99bbe8 0px; BACKGROUND: = white; OVERFLOW: hidden; BORDER-LEFT: #99bbe8 1px solid; BORDER-BOTTOM: = #99bbe8 1px solid; POSITION: relative } .x-panel-bbar .x-toolbar { BORDER-RIGHT: #99bbe8 1px solid; PADDING-RIGHT: 2px; BORDER-TOP: = #99bbe8 0px; PADDING-LEFT: 2px; PADDING-BOTTOM: 2px; OVERFLOW: hidden; = BORDER-LEFT: #99bbe8 1px solid; PADDING-TOP: 2px; BORDER-BOTTOM: #99bbe8 = 1px solid } .x-panel-tbar .x-toolbar { BORDER-RIGHT: #99bbe8 1px solid; PADDING-RIGHT: 2px; BORDER-TOP: = #99bbe8 0px; PADDING-LEFT: 2px; PADDING-BOTTOM: 2px; OVERFLOW: hidden; = BORDER-LEFT: #99bbe8 1px solid; PADDING-TOP: 2px; BORDER-BOTTOM: #99bbe8 = 1px solid } .x-panel-tbar-noheader .x-toolbar { BORDER-TOP: #99bbe8 1px solid; BORDER-BOTTOM: 0px } .x-panel-mc .x-panel-tbar .x-toolbar { BORDER-TOP: #99bbe8 1px solid; BORDER-BOTTOM: 0px } .x-panel-body-noheader { BORDER-TOP: #99bbe8 1px solid } .x-panel-mc .x-panel-body { BORDER-TOP: #99bbe8 1px solid } .x-panel-header { OVERFLOW: hidden; ZOOM: 1 } .x-panel-tl .x-panel-header { BORDER-RIGHT: 0px; PADDING-RIGHT: 0px; BORDER-TOP: 0px; PADDING-LEFT: = 0px; BACKGROUND: none transparent scroll repeat 0% 0%; PADDING-BOTTOM: = 4px; FONT: bold 11px tahoma,arial,verdana,sans-serif; BORDER-LEFT: 0px; = COLOR: #15428b; PADDING-TOP: 5px; BORDER-BOTTOM: 0px } .x-panel-tl .x-panel-icon { BACKGROUND-POSITION: 0px 4px; PADDING-LEFT: 20px! important; = BACKGROUND-REPEAT: no-repeat; ZOOM: 1 } .x-window-tl .x-panel-icon { BACKGROUND-POSITION: 0px 4px; PADDING-LEFT: 20px! important; = BACKGROUND-REPEAT: no-repeat; ZOOM: 1 } .x-panel-inline-icon { BACKGROUND-POSITION: 0px 0px; MARGIN-TOP: -1px; MARGIN-BOTTOM: -1px; = VERTICAL-ALIGN: middle; WIDTH: 16px; MARGIN-RIGHT: 4px; = BACKGROUND-REPEAT: no-repeat; HEIGHT: 16px } .x-panel-tc { BACKGROUND: url(../images/default/panel/top-bottom.gif) repeat-x 0px = 0px; OVERFLOW: hidden } .ext-strict .ext-ie7 .x-panel-tc { OVERFLOW: visible } .x-panel-tl { PADDING-LEFT: 6px; BACKGROUND: = url(../images/default/panel/corners-sprite.gif) no-repeat 0px 0px; = BORDER-BOTTOM: #99bbe8 1px solid; ZOOM: 1 } .x-panel-tr { PADDING-RIGHT: 6px; BACKGROUND: = url(../images/default/panel/corners-sprite.gif) no-repeat right 0px; = ZOOM: 1 } .x-panel-bc { BACKGROUND: url(../images/default/panel/top-bottom.gif) repeat-x 0px = bottom; ZOOM: 1 } .x-panel-bc .x-panel-footer { ZOOM: 1 } .x-panel-bl { PADDING-LEFT: 6px; BACKGROUND: = url(../images/default/panel/corners-sprite.gif) no-repeat 0px bottom; = ZOOM: 1 } .x-panel-br { PADDING-RIGHT: 6px; BACKGROUND: = url(../images/default/panel/corners-sprite.gif) no-repeat right bottom; = ZOOM: 1 } .x-panel-mc { BORDER-RIGHT: 0px; PADDING-RIGHT: 0px; BORDER-TOP: 0px; PADDING-LEFT: = 0px; BACKGROUND: #dfe8f6; PADDING-BOTTOM: 0px; MARGIN: 0px; FONT: 11px = tahoma,arial,helvetica,sans-serif; BORDER-LEFT: 0px; PADDING-TOP: 6px; = BORDER-BOTTOM: 0px } .x-panel-mc .x-panel-body { BORDER-RIGHT: 0px; BORDER-TOP: 0px; BACKGROUND: none transparent scroll = repeat 0% 0%; BORDER-LEFT: 0px; BORDER-BOTTOM: 0px } .x-panel-ml { PADDING-LEFT: 6px; BACKGROUND: = url(../images/default/panel/left-right.gif) #fff repeat-y 0px 0px; ZOOM: = 1 } .x-panel-mr { PADDING-RIGHT: 6px; BACKGROUND: = url(../images/default/panel/left-right.gif) repeat-y right 0px; ZOOM: 1 } .x-panel-bc .x-panel-footer { PADDING-BOTTOM: 6px } .x-panel-nofooter .x-panel-bc { FONT-SIZE: 0px; LINE-HEIGHT: 0; HEIGHT: 6px } .x-panel-nofooter .x-window-bc { FONT-SIZE: 0px; LINE-HEIGHT: 0; HEIGHT: 6px } .x-panel-bwrap { LEFT: 0px; OVERFLOW: hidden; ZOOM: 1; TOP: 0px } .x-panel-body { OVERFLOW: hidden; ZOOM: 1 } .x-panel-collapsed .x-resizable-handle { DISPLAY: none } .ext-gecko .x-panel-animated DIV { OVERFLOW: hidden! important } .x-plain-body { OVERFLOW: hidden } .x-plain-bbar .x-toolbar { PADDING-RIGHT: 2px; PADDING-LEFT: 2px; PADDING-BOTTOM: 2px; OVERFLOW: = hidden; PADDING-TOP: 2px } .x-plain-tbar .x-toolbar { PADDING-RIGHT: 2px; PADDING-LEFT: 2px; PADDING-BOTTOM: 2px; OVERFLOW: = hidden; PADDING-TOP: 2px } .x-plain-bwrap { OVERFLOW: hidden; ZOOM: 1 } .x-plain { OVERFLOW: hidden } .x-tool { BACKGROUND: url(../images/default/panel/tool-sprites.gif) no-repeat; = FLOAT: right; MARGIN-LEFT: 2px; OVERFLOW: hidden; WIDTH: 15px; CURSOR: = pointer; HEIGHT: 15px } .x-tool-toggle { BACKGROUND-POSITION: 0px -60px } .x-tool-toggle-over { BACKGROUND-POSITION: -15px -60px } .x-panel-collapsed .x-tool-toggle { BACKGROUND-POSITION: 0px -75px } .x-panel-collapsed .x-tool-toggle-over { BACKGROUND-POSITION: -15px -75px } .x-tool-close { BACKGROUND-POSITION: 0px 0px } .x-tool-close-over { BACKGROUND-POSITION: -15px 0px } .x-tool-minimize { BACKGROUND-POSITION: 0px -15px } .x-tool-minimize-over { BACKGROUND-POSITION: -15px -15px } .x-tool-maximize { BACKGROUND-POSITION: 0px -30px } .x-tool-maximize-over { BACKGROUND-POSITION: -15px -30px } .x-tool-restore { BACKGROUND-POSITION: 0px -45px } .x-tool-restore-over { BACKGROUND-POSITION: -15px -45px } .x-tool-gear { BACKGROUND-POSITION: 0px -90px } .x-tool-gear-over { BACKGROUND-POSITION: -15px -90px } .x-tool-pin { BACKGROUND-POSITION: 0px -135px } .x-tool-pin-over { BACKGROUND-POSITION: -15px -135px } .x-tool-unpin { BACKGROUND-POSITION: 0px -150px } .x-tool-unpin-over { BACKGROUND-POSITION: -15px -150px } .x-tool-right { BACKGROUND-POSITION: 0px -165px } .x-tool-right-over { BACKGROUND-POSITION: -15px -165px } .x-tool-left { BACKGROUND-POSITION: 0px -180px } .x-tool-left-over { BACKGROUND-POSITION: -15px -180px } .x-tool-up { BACKGROUND-POSITION: 0px -210px } .x-tool-up-over { BACKGROUND-POSITION: -15px -210px } .x-tool-down { BACKGROUND-POSITION: 0px -195px } .x-tool-down-over { BACKGROUND-POSITION: -15px -195px } .x-tool-refresh { BACKGROUND-POSITION: 0px -225px } .x-tool-refresh-over { BACKGROUND-POSITION: -15px -225px } .x-tool-minus { BACKGROUND-POSITION: 0px -255px } .x-tool-minus-over { BACKGROUND-POSITION: -15px -255px } .x-tool-plus { BACKGROUND-POSITION: 0px -240px } .x-tool-plus-over { BACKGROUND-POSITION: -15px -240px } .x-tool-search { BACKGROUND-POSITION: 0px -270px } .x-tool-search-over { BACKGROUND-POSITION: -15px -270px } .x-tool-save { BACKGROUND-POSITION: 0px -285px } .x-tool-save-over { BACKGROUND-POSITION: -15px -285px } .x-tool-help { BACKGROUND-POSITION: 0px -300px } .x-tool-help-over { BACKGROUND-POSITION: -15px -300px } .x-tool-print { BACKGROUND-POSITION: 0px -315px } .x-tool-print-over { BACKGROUND-POSITION: -15px -315px } .x-panel-ghost { Z-INDEX: 12000; BACKGROUND: #cbddf3; FILTER: alpha(opacity=3D65); LEFT: = 0px; OVERFLOW: hidden; POSITION: absolute; TOP: 0px; opacity: .65; = -moz-opacity: .65 } .x-panel-ghost UL { BORDER-RIGHT: #99bbe8 1px solid; PADDING-RIGHT: 0px; BORDER-TOP: = #99bbe8 0px; DISPLAY: block; PADDING-LEFT: 0px; FONT-SIZE: 0px; = PADDING-BOTTOM: 0px; MARGIN: 0px; OVERFLOW: hidden; BORDER-LEFT: #99bbe8 = 1px solid; LINE-HEIGHT: 0; PADDING-TOP: 0px; BORDER-BOTTOM: #99bbe8 1px = solid } .x-panel-ghost * { CURSOR: move! important } .x-panel-dd-spacer { BORDER-RIGHT: #99bbe8 2px dashed; BORDER-TOP: #99bbe8 2px dashed; = BORDER-LEFT: #99bbe8 2px dashed; BORDER-BOTTOM: #99bbe8 2px dashed } .x-panel-btns-ct { PADDING-RIGHT: 5px; PADDING-LEFT: 5px; PADDING-BOTTOM: 5px; = PADDING-TOP: 5px } .x-panel-btns-ct .x-btn { CLEAR: none; FLOAT: right } .x-panel-btns-ct .x-panel-btns TD { BORDER-TOP-WIDTH: 0px; PADDING-RIGHT: 0px; PADDING-LEFT: 0px; = BORDER-LEFT-WIDTH: 0px; BORDER-BOTTOM-WIDTH: 0px; PADDING-BOTTOM: 0px; = PADDING-TOP: 0px; BORDER-RIGHT-WIDTH: 0px } .x-panel-btns-ct .x-panel-btns-right TABLE { CLEAR: none; FLOAT: right } .x-panel-btns-ct .x-panel-btns-left TABLE { CLEAR: none; FLOAT: left } .x-panel-btns-ct .x-panel-btns-center { TEXT-ALIGN: center } .x-panel-btns-ct .x-panel-btns-center TABLE { MARGIN: 0px auto } .x-panel-btns-ct TABLE TD.x-panel-btn-td { PADDING-RIGHT: 3px; PADDING-LEFT: 3px; PADDING-BOTTOM: 3px; = PADDING-TOP: 3px } .x-panel-btns-ct .x-btn-focus .x-btn-left { BACKGROUND-POSITION: 0px -147px } .x-panel-btns-ct .x-btn-focus .x-btn-right { BACKGROUND-POSITION: 0px -168px } .x-panel-btns-ct .x-btn-focus .x-btn-center { BACKGROUND-POSITION: 0px -189px } .x-panel-btns-ct .x-btn-over .x-btn-left { BACKGROUND-POSITION: 0px -63px } .x-panel-btns-ct .x-btn-over .x-btn-right { BACKGROUND-POSITION: 0px -84px } .x-panel-btns-ct .x-btn-over .x-btn-center { BACKGROUND-POSITION: 0px -105px } .x-panel-btns-ct .x-btn-click .x-btn-center { BACKGROUND-POSITION: 0px -126px } .x-panel-btns-ct .x-btn-click .x-btn-right { BACKGROUND-POSITION: 0px -84px } .x-panel-btns-ct .x-btn-click .x-btn-left { BACKGROUND-POSITION: 0px -63px } ------=_NextPart_000_0000_01CAECAE.BD89CDB0 Content-Type: text/css; charset="iso-8859-1" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.ncbi.nlm.nih.gov/core/ext.ncbi/1/css/themes/xtheme-oldentrez.css .x-panel { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-STYLE: solid; BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-STYLE: = solid; BORDER-LEFT-STYLE: solid; BORDER-RIGHT-COLOR: #d0d0d0; = BORDER-BOTTOM-STYLE: solid } .x-panel-header { BORDER-RIGHT: #d0d0d0 1px solid; BORDER-TOP: #d0d0d0 1px solid; = BACKGROUND-IMAGE: url(../../img/oldentrez/panel/white-top-bottom.gif); = BORDER-LEFT: #d0d0d0 1px solid; COLOR: #333; BORDER-BOTTOM: #d0d0d0 1px = solid } .x-panel-body { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-panel-bbar .x-toolbar { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-panel-tbar .x-toolbar { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-panel-tbar-noheader .x-toolbar { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-panel-mc .x-panel-tbar .x-toolbar { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-panel-body-noheader { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-panel-mc .x-panel-body { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-panel-tl .x-panel-header { COLOR: #333 } .x-panel-tc { BACKGROUND-IMAGE: url(../../img/oldentrez/panel/top-bottom.gif) } .x-panel-tl { BORDER-LEFT-COLOR: #d0d0d0; BACKGROUND-IMAGE: = url(../../img/oldentrez/panel/corners-sprite.gif); BORDER-BOTTOM-COLOR: = #d0d0d0; BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-panel-tr { BACKGROUND-IMAGE: url(../../img/oldentrez/panel/corners-sprite.gif) } .x-panel-bc { BACKGROUND-IMAGE: url(../../img/oldentrez/panel/top-bottom.gif) } .x-panel-bl { BACKGROUND-IMAGE: url(../../img/oldentrez/panel/corners-sprite.gif) } .x-panel-br { BACKGROUND-IMAGE: url(../../img/oldentrez/panel/corners-sprite.gif) } .x-panel-mc { BACKGROUND: #f1f1f1 } .x-panel-mc .x-panel-body { BORDER-RIGHT: 0px; BORDER-TOP: 0px; BACKGROUND: none transparent scroll = repeat 0% 0%; BORDER-LEFT: 0px; BORDER-BOTTOM: 0px } .x-panel-ml { BACKGROUND-IMAGE: url(../../img/oldentrez/panel/left-right.gif) } .x-panel-mr { BACKGROUND-IMAGE: url(../../img/oldentrez/panel/left-right.gif) } .x-tool { BACKGROUND-IMAGE: url(../../img/oldentrez/panel/tool-sprites.gif) } .x-panel-ghost { BACKGROUND: #e0e0e0 } .x-panel-ghost UL { BORDER-LEFT-COLOR: #b0b0b0; BORDER-BOTTOM-COLOR: #b0b0b0; = BORDER-TOP-COLOR: #b0b0b0; BORDER-RIGHT-COLOR: #b0b0b0 } .x-grid-panel .x-panel-mc .x-panel-body { BORDER-RIGHT: #d0d0d0 1px solid; BORDER-TOP: #d0d0d0 1px solid; = BORDER-LEFT: #d0d0d0 1px solid; BORDER-BOTTOM: #d0d0d0 1px solid } .x-btn-left { BACKGROUND-IMAGE: url(../../img/oldentrez/button/btn-sprite.gif) } .x-btn-right { BACKGROUND-IMAGE: url(../../img/oldentrez/button/btn-sprite.gif) } .x-btn-center { BACKGROUND-IMAGE: url(../../img/oldentrez/button/btn-sprite.gif) } .x-border-layout-ct { BACKGROUND: #f0f0f0 } .x-accordion-hd { BACKGROUND-IMAGE: url(../../img/oldentrez/panel/light-hd.gif) } .x-layout-collapsed { BORDER-LEFT-COLOR: #e0e0e0; BORDER-BOTTOM-COLOR: #e0e0e0; = BORDER-TOP-COLOR: #e0e0e0; BACKGROUND-COLOR: #eee; BORDER-RIGHT-COLOR: = #e0e0e0 } .x-layout-collapsed-over { BACKGROUND-COLOR: #fbfbfb } .x-tip .x-tip-top { BACKGROUND-IMAGE: url(../../img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-top-left { BACKGROUND-IMAGE: url(../../img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-top-right { BACKGROUND-IMAGE: url(../../img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-ft { BACKGROUND-IMAGE: url(../../img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-ft-left { BACKGROUND-IMAGE: url(../../img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-ft-right { BACKGROUND-IMAGE: url(../../img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-bd-left { BACKGROUND-IMAGE: url(../../img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-bd-right { BACKGROUND-IMAGE: url(../../img/oldentrez/qtip/tip-sprite.gif) } .x-toolbar { BORDER-LEFT-COLOR: #d0d0d0; BACKGROUND: = url(../../img/oldentrez/toolbar/bg.gif) #f0f4f5 repeat-x left top; = BORDER-BOTTOM-COLOR: #d0d0d0; BORDER-TOP-COLOR: #d0d0d0; = BORDER-RIGHT-COLOR: #d0d0d0 } .x-toolbar BUTTON { COLOR: #444 } .x-toolbar .x-btn-menu-arrow-wrap .x-btn-center BUTTON { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/btn-arrow.gif) } .x-toolbar .x-btn-text-icon .x-btn-menu-arrow-wrap .x-btn-center BUTTON = { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/btn-arrow.gif) } .x-toolbar .x-btn-over .x-btn-left { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-over .x-btn-right { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-over .x-btn-center { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-over BUTTON { COLOR: #111 } .x-toolbar .x-btn-click .x-btn-left { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-pressed .x-btn-left { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-menu-active .x-btn-left { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-click .x-btn-right { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-pressed .x-btn-right { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-menu-active .x-btn-right { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-click .x-btn-center { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-pressed .x-btn-center { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-menu-active .x-btn-center { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .ytb-sep { BACKGROUND-IMAGE: url(../images/default/grid/grid-split.gif) } .x-tab-panel-header { BORDER-LEFT-COLOR: #d0d0d0; BACKGROUND: #eaeaea; BORDER-BOTTOM-COLOR: = #d0d0d0; BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-tab-panel-footer { BORDER-LEFT-COLOR: #d0d0d0; BACKGROUND: #eaeaea; BORDER-BOTTOM-COLOR: = #d0d0d0; BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-tab-panel-header { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-tab-panel-footer { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } UL.x-tab-strip-top { BORDER-LEFT-COLOR: #d0d0d0; BACKGROUND: = url(../../img/oldentrez/tabs/tab-strip-bg.gif) #dbdbdb repeat-x left = top; BORDER-BOTTOM-COLOR: #d0d0d0; BORDER-TOP-COLOR: #d0d0d0; = PADDING-TOP: 2px; BORDER-RIGHT-COLOR: #d0d0d0 } UL.x-tab-strip-bottom { BORDER-LEFT-COLOR: #d0d0d0; BACKGROUND-IMAGE: = url(../../img/oldentrez/tabs/tab-strip-btm-bg.gif); BORDER-BOTTOM-COLOR: = #d0d0d0; BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-tab-strip SPAN.x-tab-strip-text { COLOR: #333 } .x-tab-strip-over SPAN.x-tab-strip-text { COLOR: #111 } .x-tab-strip-active SPAN.x-tab-strip-text { COLOR: #333 } .x-tab-strip-disabled .x-tabs-text { COLOR: #aaaaaa } 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PADDING-RIGHT: 3px; BORDER-TOP: = #99bbe8 1px solid; PADDING-LEFT: 5px; BACKGROUND: = url(/core/extjs/ext-2.1/resources/images/default/panel/white-top-bottom.g= if) repeat-x 0px -1px; PADDING-BOTTOM: 4px; FONT: bold 11px/15px = tahoma,arial,verdana,sans-serif; OVERFLOW: hidden; BORDER-LEFT: #99bbe8 = 1px solid; COLOR: #15428b; PADDING-TOP: 5px; BORDER-BOTTOM: #99bbe8 1px = solid; ZOOM: 1 } .x-panel-body { BORDER-RIGHT: #99bbe8 1px solid; BORDER-TOP: #99bbe8 0px; BACKGROUND: = white; OVERFLOW: hidden; BORDER-LEFT: #99bbe8 1px solid; BORDER-BOTTOM: = #99bbe8 1px solid; POSITION: relative } .x-panel-bbar .x-toolbar { BORDER-RIGHT: #99bbe8 1px solid; PADDING-RIGHT: 2px; BORDER-TOP: = #99bbe8 0px; PADDING-LEFT: 2px; PADDING-BOTTOM: 2px; OVERFLOW: hidden; = BORDER-LEFT: #99bbe8 1px solid; PADDING-TOP: 2px; BORDER-BOTTOM: #99bbe8 = 1px solid } .x-panel-tbar .x-toolbar { BORDER-RIGHT: #99bbe8 1px solid; PADDING-RIGHT: 2px; BORDER-TOP: = #99bbe8 0px; PADDING-LEFT: 2px; PADDING-BOTTOM: 2px; OVERFLOW: hidden; = BORDER-LEFT: #99bbe8 1px solid; PADDING-TOP: 2px; BORDER-BOTTOM: #99bbe8 = 1px solid } .x-panel-tbar-noheader .x-toolbar { BORDER-TOP: #99bbe8 1px solid; BORDER-BOTTOM: 0px } .x-panel-mc .x-panel-tbar .x-toolbar { BORDER-TOP: #99bbe8 1px solid; BORDER-BOTTOM: 0px } .x-panel-body-noheader { BORDER-TOP: #99bbe8 1px solid } .x-panel-mc .x-panel-body { BORDER-TOP: #99bbe8 1px solid } .x-panel-header { OVERFLOW: hidden; ZOOM: 1 } .x-panel-tl .x-panel-header { BORDER-RIGHT: 0px; PADDING-RIGHT: 0px; BORDER-TOP: 0px; PADDING-LEFT: = 0px; BACKGROUND: none transparent scroll repeat 0% 0%; PADDING-BOTTOM: = 4px; FONT: bold 11px tahoma,arial,verdana,sans-serif; BORDER-LEFT: 0px; = COLOR: #15428b; PADDING-TOP: 5px; BORDER-BOTTOM: 0px } .x-panel-tl .x-panel-icon { BACKGROUND-POSITION: 0px 4px; PADDING-LEFT: 20px! important; = BACKGROUND-REPEAT: no-repeat; ZOOM: 1 } .x-window-tl .x-panel-icon { BACKGROUND-POSITION: 0px 4px; PADDING-LEFT: 20px! important; = BACKGROUND-REPEAT: no-repeat; ZOOM: 1 } .x-panel-inline-icon { BACKGROUND-POSITION: 0px 0px; MARGIN-TOP: -1px; MARGIN-BOTTOM: -1px; = VERTICAL-ALIGN: middle; WIDTH: 16px; MARGIN-RIGHT: 4px; = BACKGROUND-REPEAT: no-repeat; HEIGHT: 16px } .x-panel-tc { BACKGROUND: = url(/core/extjs/ext-2.1/resources/images/default/panel/top-bottom.gif) = repeat-x 0px 0px; OVERFLOW: hidden } .ext-strict .ext-ie7 .x-panel-tc { OVERFLOW: visible } .x-panel-tl { PADDING-LEFT: 6px; BACKGROUND: = url(/core/extjs/ext-2.1/resources/images/default/panel/corners-sprite.gif= ) no-repeat 0px 0px; BORDER-BOTTOM: #99bbe8 1px solid; ZOOM: 1 } .x-panel-tr { PADDING-RIGHT: 6px; BACKGROUND: = url(/core/extjs/ext-2.1/resources/images/default/panel/corners-sprite.gif= ) no-repeat right 0px; ZOOM: 1 } .x-panel-bc { BACKGROUND: = url(/core/extjs/ext-2.1/resources/images/default/panel/top-bottom.gif) = repeat-x 0px bottom; ZOOM: 1 } .x-panel-bc .x-panel-footer { ZOOM: 1 } .x-panel-bl { PADDING-LEFT: 6px; BACKGROUND: = url(/core/extjs/ext-2.1/resources/images/default/panel/corners-sprite.gif= ) no-repeat 0px bottom; ZOOM: 1 } .x-panel-br { PADDING-RIGHT: 6px; BACKGROUND: = url(/core/extjs/ext-2.1/resources/images/default/panel/corners-sprite.gif= ) no-repeat right bottom; ZOOM: 1 } .x-panel-mc { BORDER-RIGHT: 0px; PADDING-RIGHT: 0px; BORDER-TOP: 0px; PADDING-LEFT: = 0px; BACKGROUND: #dfe8f6; PADDING-BOTTOM: 0px; MARGIN: 0px; FONT: 11px = tahoma,arial,helvetica,sans-serif; BORDER-LEFT: 0px; PADDING-TOP: 6px; = BORDER-BOTTOM: 0px } .x-panel-mc .x-panel-body { BORDER-RIGHT: 0px; BORDER-TOP: 0px; BACKGROUND: none transparent scroll = repeat 0% 0%; BORDER-LEFT: 0px; BORDER-BOTTOM: 0px } .x-panel-ml { PADDING-LEFT: 6px; BACKGROUND: = url(/core/extjs/ext-2.1/resources/images/default/panel/left-right.gif) = #fff repeat-y 0px 0px; ZOOM: 1 } .x-panel-mr { PADDING-RIGHT: 6px; BACKGROUND: = url(/core/extjs/ext-2.1/resources/images/default/panel/left-right.gif) = repeat-y right 0px; ZOOM: 1 } .x-panel-bc .x-panel-footer { PADDING-BOTTOM: 6px } .x-panel-nofooter .x-panel-bc { FONT-SIZE: 0px; LINE-HEIGHT: 0; HEIGHT: 6px } .x-panel-nofooter .x-window-bc { FONT-SIZE: 0px; LINE-HEIGHT: 0; HEIGHT: 6px } .x-panel-bwrap { OVERFLOW: hidden; ZOOM: 1 } .x-panel-body { OVERFLOW: hidden; ZOOM: 1 } .x-panel-collapsed .x-resizable-handle { DISPLAY: none } .ext-gecko .x-panel-animated DIV { OVERFLOW: hidden! important } .x-plain-body { OVERFLOW: hidden } .x-plain-bbar .x-toolbar { PADDING-RIGHT: 2px; PADDING-LEFT: 2px; PADDING-BOTTOM: 2px; OVERFLOW: = hidden; PADDING-TOP: 2px } .x-plain-tbar .x-toolbar { PADDING-RIGHT: 2px; PADDING-LEFT: 2px; PADDING-BOTTOM: 2px; OVERFLOW: = hidden; PADDING-TOP: 2px } .x-plain-bwrap { OVERFLOW: hidden; ZOOM: 1 } .x-plain { OVERFLOW: hidden } .x-tool { BACKGROUND: = url(/core/extjs/ext-2.1/resources/images/default/panel/tool-sprites.gif) = no-repeat; FLOAT: right; MARGIN-LEFT: 2px; OVERFLOW: hidden; WIDTH: = 15px; CURSOR: pointer; HEIGHT: 15px } .x-tool-toggle { BACKGROUND-POSITION: 0px -60px } .x-tool-toggle-over { BACKGROUND-POSITION: -15px -60px } .x-panel-collapsed .x-tool-toggle { BACKGROUND-POSITION: 0px -75px } .x-panel-collapsed .x-tool-toggle-over { BACKGROUND-POSITION: -15px -75px } .x-tool-close { BACKGROUND-POSITION: 0px 0px } .x-tool-close-over { BACKGROUND-POSITION: -15px 0px } .x-tool-minimize { BACKGROUND-POSITION: 0px -15px } .x-tool-minimize-over { BACKGROUND-POSITION: -15px 50% } .x-tool-maximize { BACKGROUND-POSITION: 0px -30px } .x-tool-maximize-over { BACKGROUND-POSITION: -15px -30px } .x-tool-restore { BACKGROUND-POSITION: 0px -45px } .x-tool-restore-over { BACKGROUND-POSITION: -15px -45px } .x-tool-gear { BACKGROUND-POSITION: 0px -90px } .x-tool-gear-over { BACKGROUND-POSITION: -15px -90px } .x-tool-pin { BACKGROUND-POSITION: 0px -135px } .x-tool-pin-over { BACKGROUND-POSITION: -15px -135px } .x-tool-unpin { BACKGROUND-POSITION: 0px -150px } .x-tool-unpin-over { BACKGROUND-POSITION: -15px -150px } .x-tool-right { BACKGROUND-POSITION: 0px -165px } .x-tool-right-over { BACKGROUND-POSITION: -15px -165px } .x-tool-left { BACKGROUND-POSITION: 0px -180px } .x-tool-left-over { BACKGROUND-POSITION: -15px -180px } .x-tool-up { BACKGROUND-POSITION: 0px -210px } .x-tool-up-over { BACKGROUND-POSITION: -15px -210px } .x-tool-down { BACKGROUND-POSITION: 0px -195px } .x-tool-down-over { BACKGROUND-POSITION: -15px -195px } .x-tool-refresh { BACKGROUND-POSITION: 0px -225px } .x-tool-refresh-over { BACKGROUND-POSITION: -15px -225px } .x-tool-minus { BACKGROUND-POSITION: 0px -255px } .x-tool-minus-over { BACKGROUND-POSITION: -15px -255px } .x-tool-plus { BACKGROUND-POSITION: 0px -240px } .x-tool-plus-over { BACKGROUND-POSITION: -15px -240px } .x-tool-search { BACKGROUND-POSITION: 0px -270px } .x-tool-search-over { BACKGROUND-POSITION: -15px -270px } .x-tool-save { BACKGROUND-POSITION: 0px -285px } .x-tool-save-over { BACKGROUND-POSITION: -15px -285px } .x-tool-help { BACKGROUND-POSITION: 0px -300px } .x-tool-help-over { BACKGROUND-POSITION: -15px -300px } .x-tool-print { BACKGROUND-POSITION: 0px -315px } .x-tool-print-over { BACKGROUND-POSITION: -15px -315px } .x-panel-ghost { Z-INDEX: 12000; BACKGROUND: #cbddf3; FILTER: alpha(opacity=3D65); LEFT: = 0px; OVERFLOW: hidden; POSITION: absolute; TOP: 0px; opacity: .65; = -moz-opacity: .65 } .x-panel-ghost UL { BORDER-RIGHT: #99bbe8 1px solid; PADDING-RIGHT: 0px; BORDER-TOP: = #99bbe8 0px; DISPLAY: block; PADDING-LEFT: 0px; FONT-SIZE: 0px; = PADDING-BOTTOM: 0px; MARGIN: 0px; OVERFLOW: hidden; BORDER-LEFT: #99bbe8 = 1px solid; LINE-HEIGHT: 0; PADDING-TOP: 0px; BORDER-BOTTOM: #99bbe8 1px = solid } .x-panel-ghost * { CURSOR: move! important } .x-panel-dd-spacer { BORDER-RIGHT: #99bbe8 2px dashed; BORDER-TOP: #99bbe8 2px dashed; = BORDER-LEFT: #99bbe8 2px dashed; BORDER-BOTTOM: #99bbe8 2px dashed } .x-panel-btns-ct { PADDING-RIGHT: 5px; PADDING-LEFT: 5px; PADDING-BOTTOM: 5px; = PADDING-TOP: 5px } .x-panel-btns-ct .x-btn { CLEAR: none; FLOAT: right } .x-panel-btns-ct .x-panel-btns TD { BORDER-TOP-WIDTH: 0px; PADDING-RIGHT: 0px; PADDING-LEFT: 0px; = BORDER-LEFT-WIDTH: 0px; BORDER-BOTTOM-WIDTH: 0px; PADDING-BOTTOM: 0px; = PADDING-TOP: 0px; BORDER-RIGHT-WIDTH: 0px } .x-panel-btns-ct .x-panel-btns-right TABLE { CLEAR: none; FLOAT: right } .x-panel-btns-ct .x-panel-btns-left TABLE { CLEAR: none; FLOAT: left } .x-panel-btns-ct .x-panel-btns-center { TEXT-ALIGN: center } .x-panel-btns-ct .x-panel-btns-center TABLE { MARGIN: 0px auto } .x-panel-btns-ct TABLE TD.x-panel-btn-td { PADDING-RIGHT: 3px; PADDING-LEFT: 3px; PADDING-BOTTOM: 3px; = PADDING-TOP: 3px } .x-panel-btns-ct .x-btn-focus .x-btn-left { BACKGROUND-POSITION: 0px -147px } .x-panel-btns-ct .x-btn-focus .x-btn-right { BACKGROUND-POSITION: 0px -168px } .x-panel-btns-ct .x-btn-focus .x-btn-center { BACKGROUND-POSITION: 0px -189px } .x-panel-btns-ct .x-btn-over .x-btn-left { BACKGROUND-POSITION: 0px -63px } .x-panel-btns-ct .x-btn-over .x-btn-right { BACKGROUND-POSITION: 0px -84px } .x-panel-btns-ct .x-btn-over .x-btn-center { BACKGROUND-POSITION: 0px -105px } .x-panel-btns-ct .x-btn-click .x-btn-center { BACKGROUND-POSITION: 0px -126px } .x-panel-btns-ct .x-btn-click .x-btn-right { BACKGROUND-POSITION: 0px -84px } .x-panel-btns-ct .x-btn-click .x-btn-left { BACKGROUND-POSITION: 0px -63px } .x-btn-menu-wrap { WIDTH: 0px! important } .x-menu { BACKGROUND: #f0f0f0 0px 0px } .x-menu-list-item IMG { DISPLAY: none } .x-menu-list-item A.x-menu-item { PADDING-LEFT: 8px } .port H1.x-panel-header-text { PADDING-RIGHT: 0px; PADDING-LEFT: 0px; FONT-SIZE: 100%; PADDING-BOTTOM: = 0px; MARGIN: 0px; PADDING-TOP: 0px } .port H2.x-panel-header-text { PADDING-RIGHT: 0px; PADDING-LEFT: 0px; FONT-SIZE: 100%; PADDING-BOTTOM: = 0px; MARGIN: 0px; PADDING-TOP: 0px } .port H3.x-panel-header-text { PADDING-RIGHT: 0px; PADDING-LEFT: 0px; FONT-SIZE: 100%; PADDING-BOTTOM: = 0px; MARGIN: 0px; PADDING-TOP: 0px } .port H4.x-panel-header-text { PADDING-RIGHT: 0px; PADDING-LEFT: 0px; FONT-SIZE: 100%; PADDING-BOTTOM: = 0px; MARGIN: 0px; PADDING-TOP: 0px } .port H5.x-panel-header-text { PADDING-RIGHT: 0px; PADDING-LEFT: 0px; FONT-SIZE: 100%; PADDING-BOTTOM: = 0px; MARGIN: 0px; PADDING-TOP: 0px } .port H6.x-panel-header-text { PADDING-RIGHT: 0px; PADDING-LEFT: 0px; FONT-SIZE: 100%; PADDING-BOTTOM: = 0px; MARGIN: 0px; PADDING-TOP: 0px } DIV.x-panel-body { PADDING-RIGHT: 5px; PADDING-LEFT: 5px; PADDING-BOTTOM: 5px; = PADDING-TOP: 5px } .port .x-panel-header { PADDING-RIGHT: 3px; PADDING-LEFT: 5px; PADDING-BOTTOM: 4px; = PADDING-TOP: 5px } .x-panel { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-STYLE: solid; BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-STYLE: = solid; BORDER-LEFT-STYLE: solid; BORDER-RIGHT-COLOR: #d0d0d0; = BORDER-BOTTOM-STYLE: solid } .x-panel-header { BORDER-RIGHT: #d0d0d0 1px solid; BORDER-TOP: #d0d0d0 1px solid; = BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/panel/white-top-bottom.gif); = BORDER-LEFT: #d0d0d0 1px solid; COLOR: #333; BORDER-BOTTOM: #d0d0d0 1px = solid } .x-panel-body { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-panel-bbar .x-toolbar { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-panel-tbar .x-toolbar { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-panel-tbar-noheader .x-toolbar { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-panel-mc .x-panel-tbar .x-toolbar { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-panel-body-noheader { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-panel-mc .x-panel-body { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-panel-tl .x-panel-header { COLOR: #333 } .x-panel-tc { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/panel/top-bottom.gif) } .x-panel-tl { BORDER-LEFT-COLOR: #d0d0d0; BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/panel/corners-sprite.gif); = BORDER-BOTTOM-COLOR: #d0d0d0; BORDER-TOP-COLOR: #d0d0d0; = BORDER-RIGHT-COLOR: #d0d0d0 } .x-panel-tr { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/panel/corners-sprite.gif) } .x-panel-bc { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/panel/top-bottom.gif) } .x-panel-bl { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/panel/corners-sprite.gif) } .x-panel-br { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/panel/corners-sprite.gif) } .x-panel-mc { BACKGROUND: #f1f1f1 } .x-panel-mc .x-panel-body { BORDER-RIGHT: 0px; BORDER-TOP: 0px; BACKGROUND: none transparent scroll = repeat 0% 0%; BORDER-LEFT: 0px; BORDER-BOTTOM: 0px } .x-panel-ml { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/panel/left-right.gif) } .x-panel-mr { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/panel/left-right.gif) } .x-tool { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/panel/tool-sprites.gif) } .x-panel-ghost { BACKGROUND: #e0e0e0 } .x-panel-ghost UL { BORDER-LEFT-COLOR: #b0b0b0; BORDER-BOTTOM-COLOR: #b0b0b0; = BORDER-TOP-COLOR: #b0b0b0; BORDER-RIGHT-COLOR: #b0b0b0 } .x-grid-panel .x-panel-mc .x-panel-body { BORDER-RIGHT: #d0d0d0 1px solid; BORDER-TOP: #d0d0d0 1px solid; = BORDER-LEFT: #d0d0d0 1px solid; BORDER-BOTTOM: #d0d0d0 1px solid } .x-btn-left { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/button/btn-sprite.gif) } .x-btn-right { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/button/btn-sprite.gif) } .x-btn-center { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/button/btn-sprite.gif) } .x-border-layout-ct { BACKGROUND: #f0f0f0 } .x-accordion-hd { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/panel/light-hd.gif) } .x-layout-collapsed { BORDER-LEFT-COLOR: #e0e0e0; BORDER-BOTTOM-COLOR: #e0e0e0; = BORDER-TOP-COLOR: #e0e0e0; BACKGROUND-COLOR: #eee; BORDER-RIGHT-COLOR: = #e0e0e0 } .x-layout-collapsed-over { BACKGROUND-COLOR: #fbfbfb } .x-tip .x-tip-top { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-top-left { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-top-right { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-ft { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-ft-left { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-ft-right { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-bd-left { BACKGROUND-IMAGE: = 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elmnts.length; i < len; i++)=0A= {=0A= if (elmnts.item(i).className.indexOf(className, " ") = !=3D -1)=0A= {=0A= elmnts.item(i).innerHTML =3D innerHTML;=0A= unObscuredEmails[className] =3D true=0A= =0A= }=0A= }=0A= }=0A= }=0A= catch(e){=0A= }=0A= }=0A= =0A= //=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= function pubMedDbLinkSubmit(control) {=0A= try{=0A= if (control.pubmedOption)=0A= control =3D control.pubmedOption=0A= if (control.options)=0A= location.href =3D = control.options[control.options.selectedIndex].value;=0A= }=0A= catch(e){}=0A= return false;=0A= }=0A= =0A= //=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= // elements "a", "area" with "ref" attribute report to redirect utility = before dereferencing link=0A= //=0A= function initRedirectClicks(report_url) {=0A= =0A= if (report_url && typeof jQuery !=3D 'undefined')=0A= jQuery(document).click(function(e) {=0A= =0A= //=0A= if (!e) return true;=0A= //=0A= if (e.shiftKey || e.altKey || e.ctrlKey) return true;=0A= //=0A= var target =3D jQuery(e.target).closest("a[ref], area[ref]");=0A= if (!target || target.length =3D=3D 0) return true;=0A= //=0A= var ref =3D target.attr("ref");=0A= var href =3D target.attr("href")=0A= =0A= // special processing of href element for pubmed's authors=0A= if (typeof (href) !=3D 'undefined' && = href.indexOf('sites/entrez') && href.indexOf('%5Bauth%5D'))=0A= {=0A= var newHref =3D replacePubMedUnsupportedChars(href);=0A= if (newHref !=3D href)=0A= target.attr("href", newHref)=0A= }=0A= =0A= // append ref with value of href if 'redirect-to-url' is = missing in ref.=0A= if (typeof (ref) !=3D 'undefined' && = ref.indexOf('redirect-to-url') =3D=3D -1)=0A= {=0A= ref =3D ref + '&redirect-to-url=3D' + = encodeURIComponent(href)=0A= //=0A= jQuery.ajax({=0A= type: "HEAD",=0A= url: report_url + '?' + ref,=0A= timeout: 1000,=0A= async: false=0A= });=0A= }=0A= =0A= return true;=0A= });=0A= };=0A= =0A= // function to replace unsupported charachters in author names to be = searchable in PubMed database.=0A= function replacePubMedUnsupportedChars (str)=0A= {=0A= // replace low 128 chars automatically=0A= str =3D str.replace(/%26%23(x000[0-7][0-9a-f])%3b/ig,=0A= function($0, $1){=0A= return (String.fromCharCode('0' + $1))=0A= }=0A= )=0A= // replace others based on map and if it is not in the map replace = with empty string.=0A= str =3D = str.replace(/%26%23(x[0-9a-f][0-9a-f][0-9a-f][0-9a-f][0-9a-f])%3b/ig,=0A= function($0, $1){=0A= return (pubmedUnsupportedCharMap[$1] ? = pubmedUnsupportedCharMap[$1] : '')=0A= }=0A= )=0A= return str;=0A= }=0A= //=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= // Based on script written by Dean Edwards, 2005=0A= // http://dean.edwards.name/=0A= =0A= var pmc_script =3D {=0A= addEvent: function(element, type, handler) {=0A= // assign each event handler a unique ID=0A= if (!handler.$$guid) handler.$$guid =3D this.addEvent_guid++;=0A= // create a hash table of event types for the element=0A= if (!element.events) element.events =3D {};=0A= // create a hash table of event handlers for each element/event pair=0A= var handlers =3D element.events[type];=0A= if (!handlers) {=0A= handlers =3D element.events[type] =3D {};=0A= // store the existing event handler (if there is one)=0A= if (element["on" + type]) {=0A= handlers[0] =3D element["on" + type];=0A= }=0A= }=0A= // store the event handler in the hash table=0A= handlers[handler.$$guid] =3D handler;=0A= // assign a global event handler to do all the work=0A= element["on" + type] =3D handleEvent;=0A= =0A= =0A= function handleEvent(event) {=0A= var returnValue =3D true;=0A= // grab the event object (IE uses a global event object)=0A= event =3D event || fixEvent(window.event);=0A= // get a reference to the hash table of event handlers=0A= var handlers =3D this.events[event.type];=0A= // execute each event handler=0A= for (var i in handlers) {=0A= this.$$handleEvent =3D handlers[i];=0A= if (this.$$handleEvent(event) =3D=3D=3D false) {=0A= returnValue =3D false;=0A= }=0A= }=0A= return returnValue;=0A= };=0A= =0A= function fixEvent(event) {=0A= // add W3C standard event methods=0A= event.preventDefault =3D fixEvent.preventDefault;=0A= event.stopPropagation =3D fixEvent.stopPropagation;=0A= return event;=0A= };=0A= =0A= fixEvent.preventDefault =3D function() {=0A= this.returnValue =3D false;=0A= };=0A= =0A= fixEvent.stopPropagation =3D function() {=0A= this.cancelBubble =3D true;=0A= };=0A= },=0A= =0A= // a counter used to create unique IDs=0A= addEvent_guid: 1,=0A= =0A= removeEvent: function(element, type, handler) {=0A= // delete the event handler from the hash table=0A= if (element.events && element.events[type]) {=0A= delete element.events[type][handler.$$guid];=0A= }=0A= }=0A= }=0A= =0A= =0A= // = *************************************************************************= ***=0A= // implementation of figure's popup using jQuery and = jQuery.fn.hoverIntent lib=0A= // it set appropriate handlers for all "a" elements with "figpopup" = class name.=0A= // = *************************************************************************= ***=0A= if (typeof jQuery !=3D 'undefined' && typeof jQuery.fn.hoverIntent !=3D = 'undefined') {=0A= (function($j) {=0A= // = =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D hoverHandlers = =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=0A= var hoverHandlers =3D function (opts) {=0A= this.config =3D {}=0A= this.self =3D this;=0A= this.__init(opts)=0A= }=0A= =0A= $j.fn.extend(hoverHandlers.prototype, {=0A= //=0A= __init: function(opts) {=0A= $j.fn.extend(this.config, opts)=0A= },=0A= //=0A= over: function (el) {=0A= var canvas =3D $j('.large-thumb-canvas', el)=0A= var prnt =3D canvas.parent();=0A= var win =3D $j(window)=0A= =0A= //=0A= if (canvas && prnt && win)=0A= {=0A= =0A= // collect necessary coordinates from all = intresting objects=0A= canvas.coords =3D this._x_coords(canvas, = 'canvas')=0A= prnt.coords =3D this._x_coords(prnt, = 'parent')=0A= win.coords =3D this._x_coords(win, = 'window')=0A= =0A= // replace @src with value of @hires, because = href hold high resolution image and src low one.=0A= $j('img', canvas).attr('src',=0A= function(){=0A= var hires =3D $j(this).attr("hires");=0A= return (typeof (hires) !=3D = 'undefined' && hires !=3D this.src)=0A= ? hires : this.src=0A= }=0A= )=0A= =0A= // make arrangement of canvas in the view port = nearby parent element.=0A= var cnvsRltvToPrnt =3D = this._x_arrange_canvas(canvas.coords, prnt.coords, win.coords)=0A= =0A= // visualize the canvas with images.=0A= canvas.css('top', cnvsRltvToPrnt.top + 'px')=0A= canvas.css('left', cnvsRltvToPrnt.left + 'px')=0A= canvas.css('display', 'block')=0A= } // canvas=0A= }, // over=0A= //=0A= out: function (el) {=0A= var canvas =3D $j('.large-thumb-canvas', el)=0A= canvas.css('display', 'none')=0A= },=0A= //=0A= _x_offset: function(el, elname) {=0A= var c =3D {}=0A= if (el[0] =3D=3D window )=0A= c =3D this._x_scroll(el, elname)=0A= else=0A= c =3D el.offset()=0A= //console.info('%s.offset {top,left} =3D {%s, %s}', = elname, c.top, c.left)=0A= return c=0A= },=0A= _x_scroll: function(el, elname) {=0A= var c =3D {top: el.scrollTop(), left: = el.scrollLeft()}=0A= //console.info('%s.scroll {top,left} =3D {%s, %s}', = elname, c.top, c.left)=0A= return c=0A= },=0A= _x_width: function(el, elname) {=0A= var w =3D el.outerWidth() || el.width()=0A= //console.info('%s.width =3D %s; outerWidth =3D = %s; width =3D %s', elname, w, el.outerWidth(), el.width())=0A= //IE: alert(elname + '.width =3D ' + w + '; = outerWidth =3D ' + el.outerWidth() + 'width =3D ' + el.width())=0A= return w=0A= },=0A= _x_height: function(el, elname) {=0A= var h =3D el.outerHeight() || el.height()=0A= // console.info('%s.height =3D %s', elname, h)=0A= return h=0A= },=0A= _x_coords: function(el, elname) {=0A= var size =3D { width: this._x_width (el, elname), = height: this._x_height(el, elname)}=0A= var coords =3D {=0A= scroll: this._x_scroll(el, elname),=0A= width: size.width,=0A= height: size.height,=0A= offset: this._x_offset(el, elname),=0A= size: size=0A= }=0A= return coords=0A= },=0A= _x_get_rltv_coord: function(trgtObj, baseObj, = label) {=0A= var c =3D {top: trgtObj.top - baseObj.top, left: = trgtObj.left - baseObj.left}=0A= //console.info("%s {top: %s, left: %s}", label, = c.top, c.left)=0A= return c=0A= },=0A= //=0A= _x_get_empty_space: function(objCoords, = objSize, viewPortCoords, viewPortSize, label) {=0A= var objRelToViewPort =3D = this._x_get_rltv_coord(objCoords, viewPortCoords, '_x_get_empty_space: = for ' + label);=0A= var c =3D {above: objRelToViewPort.top,=0A= below: viewPortSize.height - = (objRelToViewPort.top + objSize.height),=0A= left: objRelToViewPort.left,=0A= right: viewPortSize.width - = (objRelToViewPort.left + objSize.width)}=0A= $j.each(c, function(k, v){c[k] =3D (v < 0 ? 0 : v)})=0A= //console.info("%s {above: %s, below: %s, left: %s, = right: %s}", label, c.above, c.below, c.left, c.right)=0A= return c=0A= },=0A= //=0A= _x_get_bigest_space_area_name: function(spaces, label) {=0A= var sArr =3D [];=0A= for (k in spaces){ sArr[sArr.length] =3D {k: k, v: = spaces[k]} }=0A= // sort in reverse order=0A= sArr.sort (function(a,b){return ( a.v < b.v ? 1 : ( = a.v > b.v ? - 1 : 0 ) )})=0A= // console.info('%s: %s', label, sArr[0].k)=0A= return sArr[0].k=0A= },=0A= //=0A= _x_get_space_ratios: function(spaces, = viewPortSize, label) {=0A= var ratios =3D {above: 0, left: 0}=0A= if (viewPortSize.height > 0)=0A= ratios.above =3D spaces.above / = viewPortSize.height=0A= if (viewPortSize.width > 0)=0A= ratios.left =3D spaces.left / viewPortSize.width=0A= // console.info('ratio: %s {above: %s, left: %s}', = label, ratios.above, ratios.left)=0A= return ratios=0A= },=0A= _x_arrange_canvas: function(c_c, prnt_c, = viewp_c) {=0A= // then calculate empty space areas around parent = element of the canvas, which is ususally an anchor ("a" element)=0A= var emptySpacesArndPrntInViewPort =3D = this._x_get_empty_space (prnt_c.offset, prnt_c.size, viewp_c.offset, = viewp_c.size, 'emptySpacesArndPrntInWinPort')=0A= =0A= // get the area name, where the most linear space = avaiable=0A= var areaName =3D = this._x_get_bigest_space_area_name(emptySpacesArndPrntInViewPort, = viewp_c.size, 'spacios areaName')=0A= =0A= // calculate the proportions of area to be taken by = canvas in empty space area=0A= // relativly to the parent element.=0A= var ratios =3D = this._x_get_space_ratios(emptySpacesArndPrntInViewPort, viewp_c.size, = 'ratios')=0A= =0A= // calculate parent's coordinates relative to view = port=0A= var prntRltvToViewPort =3D = this._x_get_rltv_coord(prnt_c.offset, viewp_c.offset, = 'prntRltvToViewPort')=0A= =0A= // declare canvas relative coordinates=0A= var cnvsRltvToPrnt =3D {top: 0, left: 0}=0A= =0A= // choose appropriate location for placing canvas.=0A= // and choose the 1st element of an array as the one = with the biggest area around parent of canvas.=0A= // console.info ('place it at the %s', = bigestEmptySpaceAreaName)=0A= // calculations are relative to the left corner of = the parent element of canvas. (it has to have the css property = position:relative)=0A= switch (areaName)=0A= {=0A= case 'above':=0A= cnvsRltvToPrnt.top =3D - c_c.height=0A= cnvsRltvToPrnt.left =3D prnt_c.width * 0.5 - = c_c.width * ratios.left=0A= break;=0A= case 'below':=0A= cnvsRltvToPrnt.top =3D prnt_c.height=0A= cnvsRltvToPrnt.left =3D prnt_c.width * 0.5 - = c_c.width * ratios.left=0A= break;=0A= case 'left':=0A= cnvsRltvToPrnt.left =3D - c_c.width=0A= cnvsRltvToPrnt.top =3D prnt_c.height * 0.5 = - c_c.height * ratios.above=0A= break;=0A= case 'right':=0A= cnvsRltvToPrnt.left =3D prnt_c.width=0A= cnvsRltvToPrnt.top =3D prnt_c.height * 0.5 = - c_c.height * ratios.above=0A= break;=0A= }=0A= =0A= // recalculate canvas' coordinates relative to = parent into coordinates relative to view port.=0A= var cnvsRltvToViewPort =3D {=0A= top: prntRltvToViewPort.top + = cnvsRltvToPrnt.top,=0A= left: prntRltvToViewPort.left + = cnvsRltvToPrnt.left=0A= }=0A= //console.info("cnvsRltvToPrnt {top:%s, left: %s}", = cnvsRltvToPrnt.top, cnvsRltvToPrnt.left)=0A= //console.info("cnvsRltvToViewPort {top:%s, left: = %s}", cnvsRltvToViewPort.top, cnvsRltvToViewPort.left)=0A= =0A= // adjust relative position of canvas to the window = if calculated values=0A= // are forcing canvas go out of view port=0A= // next order should be preserved to keep left top = corner visible always=0A= =0A= // adjust right side and move a bit to the left=0A= if (cnvsRltvToViewPort.left + c_c.width > = viewp_c.width)=0A= {=0A= var horAdj =3D c_c.width - (viewp_c.width - = cnvsRltvToViewPort.left)=0A= cnvsRltvToPrnt.left -=3D horAdj=0A= cnvsRltvToViewPort.left -=3D horAdj=0A= //console.log('adjust right side and move to = the left %spx', horizontalAdjustment)=0A= }=0A= =0A= // adjust below side and move to the top=0A= if (cnvsRltvToViewPort.top + c_c.height > = viewp_c.height)=0A= {=0A= var vertAdj =3D c_c.height - (viewp_c.height - = cnvsRltvToViewPort.top)=0A= cnvsRltvToPrnt.top -=3D vertAdj=0A= cnvsRltvToViewPort.top -=3D vertAdj=0A= // console.log('adjust below side and move to = the top %spx', verticalAdjustment)=0A= }=0A= =0A= // adjust left side and move to the right=0A= if (cnvsRltvToViewPort.left < 0)=0A= {=0A= // console.log('adjust left side and move to the = right %spx', -(cnvsLeftRelativeToWindowPort))=0A= cnvsRltvToPrnt.left -=3D = cnvsRltvToViewPort.left=0A= cnvsRltvToViewPort.left =3D 0=0A= }=0A= // adjust above side and move to the bottom=0A= if (cnvsRltvToViewPort.top < 0)=0A= {=0A= // console.log('adjust above side and move to = the bottom %spx', -(cnvsTopRelativeToWindowPort))=0A= cnvsRltvToPrnt.top -=3D = cnvsRltvToViewPort.top=0A= cnvsRltvToViewPort.top =3D 0=0A= }=0A= // console.info("cnvsRltvToPrnt adjusted {top: %s, = left: %s}", cnvsRltvToPrnt.top, cnvsRltvToPrnt.left)=0A= // console.info("cnvsRltvToViewPort adjusted {top: = %s, left: %s}", cnvsRltvToViewPort.top, cnvsRltvToViewPort.left)=0A= return cnvsRltvToPrnt=0A= }=0A= })=0A= // = =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D end of hoverHandlers = =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=0A= =0A= =0A= // = =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D $j.fn.figPopup = =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= function hoverOverHandler () {=0A= var h =3D new hoverHandlers();=0A= h.over(this)=0A= }=0A= =0A= function hoverOutHandler () {=0A= var h =3D new hoverHandlers();=0A= h.out(this)=0A= }=0A= =0A= $j.fn.figPopup =3D function(opts){=0A= var config =3D {=0A= interval: 500,=0A= timeout: 0,=0A= over: hoverOverHandler, // handler onMouseOver=0A= out: hoverOutHandler // handler onMouseOut=0A= }=0A= $j.extend(config, opts)=0A= return config=0A= }=0A= =0A= // = =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D end of $j.fn.figPopup = =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=0A= =0A= }) (jQuery) // end of extention of jQuery with figPopup=0A= =0A= =0A= =0A= jQuery(document).ready( function () {=0A= var fp_cfg =3D new jQuery.fn.figPopup()=0A= jQuery('a.figpopup').hoverIntent(fp_cfg)=0A= });=0A= }=0A= =0A= // end of hoverIntent routines for figures' popups=0A= // = *************************************************************************= ***=0A= // implementation of ....=0A= // = *************************************************************************= ***=0A= ------=_NextPart_000_0000_01CAECAE.BD89CDB0 Content-Type: application/octet-stream Content-Transfer-Encoding: quoted-printable Content-Location: http://www.ncbi.nlm.nih.gov/corehtml/pmc/js/noext.menu.js if (typeof(noext) =3D=3D=3D 'undefined') { noext =3D {};=20 } if (typeof jQuery =3D=3D=3D 'undefined') { throw new Error('noext.Menu: jQuery must be present'); } // Constructor noext.Menu =3D function (n, subMenuStyle) { this.n =3D n; this.subMenuStyle =3D (subMenuStyle =3D=3D=3D 'ext') ? 'opened-ext' = : 'opened'; this.firstLi =3D this.n.children('li'); this.subMenu =3D this.firstLi.find('ul'); this.subMenuItems =3D this.subMenu.find('li'); this.init(); noext.Menu.menuInstances.push(this); }; noext.Menu.menuInstances =3D []; noext.Menu.prototype =3D { init: function () { // add events to what we need var that =3D this; this.subMenuItems.mouseover( this.hover); // do mouseovers for = ie6 this.subMenuItems.mouseout( this.unHover); this.n.click( function (event) { that.update(event);}); // = update the menu =20 jQuery(document).click( function (event) { = that.closeAllSubMenus(event); }); // close other menus when we click one }, update: function (e) { var t =3D jQuery(e.target); =20 // don't follow link if first item, whose target is '' if (t.hasClass('first-link') ) { e.preventDefault(); } var sm =3D this.subMenu; // close other menus this.closeOtherSubMenus(sm); =20 var subMenuStyle =3D this.subMenuStyle; =20 if ( !sm.hasClass(subMenuStyle)) { 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