236 research outputs found

    An Archaic Horizon Cache from Southern Minnesota

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    Notes on a Palaeolithic Site Survey in Pakistan

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    A Statistical Analysis of Some Mississippian Projectile Points

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    Birch Lake Burial Mound Group

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    Five small prehistoric burial mounds located near Birch Lake on Prairie Island in Goodhue county of southeastern Minnesota were excavated in 1968. The secondary burial of adults in shallow pits and unaccompanied by mortuary offerings follows widespread prehistoric patterns in the upper Mississippi valley. The mortuary pottery vessel buried with the single primary burial suggests construction of the mounds during the period of initial Mississippian cultural intrusion, perhaps shortly after 1,000 A.D

    Radiation-Enhanced Therapeutic Targeting of Galectin-1 Enriched Malignant Stroma in Triple Negative Breast Cancer

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    Currently there are no FDA approved targeted therapies for Triple Negative Breast Cancer (TNBC). Ongoing clinical trials for TNBC have focused primarily on targeting the epithelial cancer cells. However, targeted delivery of cytotoxic payloads to the non-transformed tumor associated-endothelium can prove to be an alternate approach that is currently unexplored. The present study is supported by recent findings on elevated expression of stromal galectin-1 in clinical samples of TNBC and our ongoing findings on stromal targeting of radiation induced galectin-1 by the anginex-conjugated arsenic-cisplatin loaded liposomes using a novel murine tumor model. We demonstrate inhibition of tumor growth and metastasis in response to the multimodal nanotherapeutic strategy using a TNBC model with orthotopic tumors originating from 3D tumor tissue analogs (TTA) comprised of tumor cells, endothelial cells and fibroblasts. The ‘rigorous’ combined treatment regimen of radiation and targeted liposomes is also shown to be well tolerated. More importantly, the results presented provide a means to exploit clinically relevant radiation dose for concurrent receptor mediated enhanced delivery of chemotherapy while limiting overall toxicity. The proposed study is significant as it falls in line with developing combinatorial therapeutic approaches for stroma-directed tumor targeting using tumor models that have an appropriate representation of the TNBC microenvironment

    On extremum properties of orthogonal quotients matrices

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    AbstractIn this paper we explore the extremum properties of orthogonal quotients matrices. The orthogonal quotients equality that we prove expresses the Frobenius norm of a difference between two matrices as a difference between the norms of two matrices. This turns the Eckart–Young minimum norm problem into an equivalent maximum norm problem. The symmetric version of this equality involves traces of matrices, and adds new insight into Ky Fan’s extremum problems. A comparison of the two cases reveals a remarkable similarity between the Eckart–Young theorem and Ky Fan’s maximum principle. Returning to orthogonal quotients matrices we derive “rectangular” extensions of Ky Fan’s extremum principles, which consider maximizing (or minimizing) sums of powers of singular values

    Model Organisms Reveal Insight into Human Neurodegenerative Disease: Ataxin-2 Intermediate-Length Polyglutamine Expansions Are a Risk Factor for ALS

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    Model organisms include yeast Saccromyces cerevisae and fly Drosophila melanogaster. These systems have powerful genetic approaches, as well as highly conserved pathways, both for normal function and disease. Here, we review and highlight how we applied these systems to provide mechanistic insight into the toxicity of TDP-43. TDP-43 accumulates in pathological aggregates in ALS and about half of FTD. Yeast and fly studies revealed an interaction with the counterparts of human Ataxin-2, a gene whose polyglutamine repeat expansion is associated with spinocerebellar ataxia type 2. This finding raised the hypothesis that repeat expansions in ataxin-2 may associate with diseases characterized by TDP-43 pathology such as ALS. DNA analysis of patients revealed that intermediate-length polyglutamine expansions in ataxin-2 are a risk factor for ALS, such that repeat lengths are greater than normal, but lower than that associated with spinocerebellar ataxia type 2 (SCA2), and are more frequent in ALS patients than in matched controls. Moreover, repeat expansions associated with ALS are interrupted CAA-CAG sequences as opposed to the pure CAG repeat expansions typically associated with SCA2. These studies provide an example of how model systems, when extended to human cells and human patient tissue, can reveal new mechanistic insight into disease
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