990 research outputs found
Duocarmycin-based prodrugs for cancer prodrug monotherapy
No full textThe synthesis and biological evaluation of novel prodrugs based on the cytotoxic antibiotic duocarmycin SA (1) for a selective treatment of cancer using a prodrug monotherapy (PMT) are described. Transformation of the phenol 8 with the glucuronic acid benzyl ester trichloroacetimidate 9b followed by reaction with DMAI center dot HCl (10) gives the glucuronide 11b, which is deprotected to afford the desired prodrug 4a containing a glucuronic acid moiety. In addition, the prodrug 4b with a glucuronic methyl ester unit is prepared. The cytotoxicity of the glucuronides is determined using a HTCFA- assay with IC(50) values of 610 nM for 4a and 3300 nM for 4b. In the presence of beta-glucuronidase, 4a expresses an IC(50) value of 0.9 nM and 4b of 2.1 nM resulting in QIC(50) values of about 700 for 4a and 1600 for 4b. (c) 2008 Elsevier Ltd. All rights reserved
GNSS Vulnerabilities - Providing Maximum User Protection
No full text03.06.13 KB. Ok to add to Spiral, copyright with the author
Light of the World: The Life and Legacy of Nur Jahan
No full textAbout the Author
Maggie Schuster is a recent graduate from the University of Minnesota. She graduated in May 2017 with a major in Art History and minor in Gender Women and Sexuality Studies
Synthesis of the first spacer containing prodrug of a duocarmycin analogue and determination of its biological activity
No full textThe synthesis of the first spacer containing, duocarmycin analogue prodrug 11 was realised, its biological properties evaluated and compared to its counterpart prodrug 2 without a spacer unit. The synthesis comprises the manufacture of the new acetylated derivatives 19 and 20b of two double spacer systems, their activation and coupling to the pharmacophoric seco-drug (+)-3. Unprecedented biological results were found as the new prodrug 11 showed a fairly low QIC(50) value of 20, but on the other hand a high stability and very low DNA alkylation efficiency. These findings indicate a changed cytostatic mode of action induced by the self-immolative spacer moiety which was employed
Asymmetric Synthesis and Biological Evaluation of Glycosidic Prodrugs for a Selective Cancer Therapy
No full textA severe limitation in cancer therapy is the often insufficient differentiation between malign and benign tissue using known chemotherapeutics. One approach to decrease side effects is antibody-directed enzyme prodrug therapy (ADEPT). We have developed new glycosidic prodrugs such as (-)-(1S)-26b based on the antibiotic (+)-duocarmycin SA ((+)-1) with a QIC(50) value of 3500 (QIC(50)=IC(50) of prodrug/IC(50) of prodrug+enzyme) and an IC(50) value for the corresponding drug (prodrug + enzyme) of 16pM. The asymmetric synthesis of the precursor (-)-(1S)-19 was performed by arylation of the enantiomerically pure epoxide (+)-(S)29 (>= 98% ee)
Near Wall PIV-Measurements on the Windward Slope of a Hill
No full textThe turbulent flow over periodic hills was measured near to the wall, using planar Particle-Image-Velocimetry (PIV) at high spatial resolution. Our focus is on the near wall turbulence structure on the windward slope of the hill. For large-eddy simulation (LES) we suspect that, if this was not predicted accurately, it affects the prediction of the velocity profiles over the hill crest which in turn will affect the recirculation length downstream of the hill. Regarding the time averaged velocities, we were able to resolve the linear viscous region of the boundary layer. The velocity distribution and also the Reynolds stress does not comply with the law of the wall as it is valid for a turbulent boundary layer at equilibrium
European psychotraumatology – alongside the recent European history
No full textThis article outlines a personal reflection of experiences within the field of traumatic stress, especially in relation to specific events, which affected the author's professional life. Conclusions for further challenges for European Society for Traumatic Stress Studies (ESTSS) are delineated. ESTSS's role in the global network of traumatic stress societies is discussed. This is a personal view of Brigitte Lueger-Schuster, president of ESTSS on behalf of the 20th birthday of ESTSS
APPROXIMATING BEPPO LEVI’S PRINCIPIO DI APPROSSIMAZIONE
No full textWe try to recast in modern terms a choice principle conceived by Beppo Levi, who called it the Approximation Principle (AP). Up to now, there was almost no discussion about Levi’s contribution, due to the quite obscure formulation of AP the author has chosen. After briefly reviewing the historical and philosophical surroundings of Levi’s proposal, we undertake our own attempt at interpreting AP. The idea underlying the principle, as well as the supposed faithfulness of our version to Levi’s original intention, are then discussed. Finally, an application of AP to a property of metric spaces is presented, with the aim of showing how AP may work in contexts where other forms of choice are commonly at use
Preliminary report on effect of irrigation on major berry crops in the Willamette Valley
No full textby C.E. Schuster, R.S. Besse, G.L. Rygg, and W.L. Powers.This archived document is maintained by the State Library of Oregon as part of the Oregon Documents Depository Program. It is for informational purposes and may not be suitable for legal purposes.Mode of access: Internet from the Oregon Government Publications Collection.Text in English
The guardians of cell fate: protective mechanisms that ensure proper cell fate and patterning during imaginal disc regeneration in drosophila
No full textRegenerating tissue must replace lost structures with cells of the proper identity and pattern in order to restore function. This thesis will describe two major insights into how patterning and cell fate is maintained and restored during the late phases of regeneration in the wing imaginal disc of Drosophila. First, the identification of taranis as a regeneration-specific patterning gene and its subsequent characterization as a factor that is required to protect the regenerating cells in the wing imaginal disc from inappropriate posterior to anterior cell fate changes that are induced by the powerful JNK signaling cascade at the wound misregulating the expression of engrailed. The other chapter will detail the identification of the pioneer transcription factor Zelda as being upstream of taranis expression during regeneration. Zelda is found to be expressed at the same place and time as Taranis, and reduction of Zelda levels results in profound anterior and posterior patterning defects. Speculation is provided suggesting that Zelda may also be essential for the large developmental transition from a program devoted to regenerative growth to the repatterning phase that allows for the restoration of cell fate and patterning genes that was lost earlier in regeneration. This work describes identification of a novel gene regulatory network essential for patterning and cell fate during regeneration.Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2020-08-01The student, Keaton Schuster, accepted the attached license on 2018-07-10 at 12:45.The student, Keaton Schuster, submitted this Dissertation for approval on 2018-07-10 at 15:14.This Dissertation was approved for publication on 2018-07-10 at 16:18.DSpace SAF Submission Ingestion Package generated from Vireo submission #12794 on 2018-09-27 at 11:18:42Made available in DSpace on 2018-09-27T16:30:28Z (GMT). No. of bitstreams: 3
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Previous issue date: 2018-07-10Embargo set by: Seth Robbins for item 107792
Lift date: 2020-09-27T16:30:34Z
Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD systemEmbargo set by: Seth Robbins for item 107792
Lift date: 2020-09-27T16:31:43Z
Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD systemEmbargo set by: Seth Robbins for item 107792
Lift date: 2020-09-27T16:34:29Z
Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD systemU of I Only Restriction Lifted for Item 107792 on 2020-09-28T09:15:24Z
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