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Gagan Preet Emmanuel T. Oluwabusola Bruce Forbes Milne Rainer Ebel Marcel Jaspars 《International journal of molecular sciences》2022,23(22)
Monkeypox is caused by a DNA virus known as the monkeypox virus (MPXV) belonging to the Orthopoxvirus genus of the Poxviridae family. Monkeypox is a zoonotic disease where the primary significant hosts are rodents and non-human primates. There is an increasing global incidence with a 2022 outbreak that has spread to Europe in the middle of the COVID-19 pandemic. The new outbreak has novel, previously undiscovered mutations and variants. Currently, the US Food and Drug Administration (FDA) approved poxvirus treatment involving the use of tecovirimat. However, there has otherwise been limited research interest in monkeypox. Mitoxantrone (MXN), an anthracycline derivative, an FDA-approved therapeutic for treating cancer and multiple sclerosis, was previously reported to exhibit antiviral activity against the vaccinia virus and monkeypox virus. In this study, virtual screening, molecular docking analysis, and pharmacophore ligand-based modelling were employed on anthracene structures (1-13) closely related to MXN to explore the potential repurposing of multiple compounds from the PubChem library. Four chemical structures (2), (7), (10) and (12) show a predicted high binding potential to suppress viral replication. 相似文献
113.
DR LeMay M Kittaka EM Gordon B Gray MF Stins JG McComb S Jovanovic P Tabrizi MH Weiss R Bartus WF Anderson BV Zlokovic 《Canadian Metallurgical Quarterly》1998,9(7):989-995
Herpes simplex virus thymidine kinase (HSV-tk) gene therapy for brain tumors depends on ganciclovir (GCV) and its transport across the blood-brain tumor barrier (BBTB). We examined whether RMP-7, the bradykinin analog and potent BBTB permeabilizer, could enhance the efficacy of GCV treatment of brain tumors by increasing the BBTB delivery of GCV. In vitro, a significant bystander cytocidal effect of GCV was shown in mixed HSV-tk-transduced (HSV-tk+) and control vector-transduced (HSV-tk-) C6 glioma cultures. A dose-dependent cytotoxic effect of GCV on untransformed C6 cells was also shown. In vivo, rats with 100% HSV-tk+ or 100% HSV-tk- intracerebral C6 gliomas were treated for 7 days with intravenous infusions of GCV alone or with GCV and RMP-7 (2.5 microg/kg/day). The growth of HSV-tk+ and HSV-tk- gliomas decreased with increasing doses of GCV. A high dosage (100 mg of GCV/kg/day) eradicated all HSV-tk- and HSV-tk+ tumors. An intermediate dosage (5 mg of GCV/kg/day) reduced the growth of HSV-tk- gliomas by 42% if given alone, and by 88% in combination with RMP-7. A low dosage (0.5 mg of GCV/kg/day) in combination with RMP-7 enhanced the regression of HSV-tk+ gliomas by 87% compared with GCV alone. Low-dose GCV was ineffective in HSV-tk- tumors. RMP-7 increased [3H] GCV tumoral uptake by 2.6- and 1.7-fold in the tumor center and periphery, respectively. We conclude that RMP-7 could be an important adjunctive treatment for suicide gene therapy of brain tumors, while an RMP-7/GCV combination may also have a significant antitumor effect in untransfected gliomas. 相似文献
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115.
Flow caused by a point sink in an otherwise stagnant fluid is studied using numerical methods based on integral-equation techniques and an asymptotic solution for small Froude number. There is a vertical wall present on a plane close to the sink, so that the flow is fully three dimensional. The fluid is of infinite depth, but a free-surface bounds it above. Steady solutions are presented for various Froude numbers and distances of the source from the wall. It is shown that the numerical results and asymptotic formula are in good agreement for small Froude numbers, but the results suggest that the non-linear solution ultimately forms some limiting structure at sufficiently large Froude number. 相似文献
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DM Edgar WF Seidel KW Gee NC Lan G Field H Xia JE Hawkinson S Wieland RB Carter PL Wood 《Canadian Metallurgical Quarterly》1997,282(1):420-429
Signal detectability was measured in three temporal conditions as a function of the bandwidth and configuration of simultaneous maskers that either did or did not spectrally overlap the signal. The 20-ms signal was 250 Hz wide and was centered at 2500 Hz (fs). Although there were marked individual differences, performance was typically poorer when signal onset came 1 ms rather than 250 ms after the onset of a 420-ms masker, and poorest when signal onset came 1 ms after the onset of a 23-ms masker. The results support the idea that two separate across-channel processes contribute to temporal changes in signal detectability. One process contributes to the improvement observed as signal onset is delayed from masker onset, and its influence is reduced by the presence of masking components at fs only when the masker extends exclusively below fs. The other process is associated with the improvement observed as masker offset is delayed from signal offset, and its influence is reduced by the presence of masking components at fs when the masker extends exclusively above, or both below and above fs. Both of these processes are primarily activated by frequencies ranging from 0.6 to 0.8fs and 1.2 to 1.4fs. The data also demonstrate that the measured critical bandwidth narrows as signal onset is delayed from masker onset. 相似文献
118.
There are several tumors and tumorlike entities of bone that do not easily fit into the specific classifications provided elsewhere in this issue. In this article, several seemingly unrelated entities are discussed, including cystic diseases of bone (simple bone cysts and aneurysmal bone cysts), Langerhans' cell histiocytosis, benign and malignant vascular tumors of bone, and adamantinoma of long bone and its relationship to osteofibrous dysplasia. 相似文献
119.
A target-field method to design circular biplanar coils for asymmetric shim and gradient fields 总被引:1,自引:0,他引:1
The paper presents a method for designing circular, shielded biplanar coils that can generate any desired field. A particular feature of these coils is that the target field may be located asymmetrically within the coil. A transverse component of the magnetic field produced by the coil is made to match a prescribed target field over the surfaces of two concentric spheres (the diameter of spherical volume) that define the target field location. The paper shows winding patterns and fields for several gradient and shim coils. It examines the effect that the finite coil size has on the winding patterns, using a Fourier-transform calculation for comparison. 相似文献
120.