Metal-Free Tandem Beckmann–Electrophilic Aromatic Substitution Cascade Affording Diaryl Imines, Ketones, Amines, and Quinazolines

A cascade reaction sequence involving a Beckmann rearrangement on benzophenone oxime followed by an electrophilic aromatic substitution (EAS) on the intermediate nitrilium ion affords N-phenyl diaryl imines that may then be hydrolyzed to ketones, or reduced to the corresponding amines. Reaction with benzonitrile afforded 2,4-diphenylquinazoline through a Beckmann–Ritter–EAS cascade

Taking Ownership: Our Pledge to Educate All of Detroit's Children

Excellent Schools Detroit represents a broad and diverse cross section of Detroit's education, government, civic and community, parent, organized labor, and philanthropic leaders who are committed to ensuring that all Detroit children receive the great education they deserve. This citywide education plan reflects months of discussions and deliberations by coalition members, as well as a series of six community meetings in November and December, youth focus groups, small group discussions with multiple stakeholders, and other outreach efforts. We appreciate the thoughtful recommendations from the many Detroiters who are as passionate as we are about the need to prepare all students for college, careers, and life in the 21st century

Susie L. Meyers Bobb letters, MSS.3658

Abstract: Correspondence between family and friends of the Bobb, Raymond, and Meyers families of Pennsylvania, Illinois, and Iowa. The letters date from 1873-1922, and most of them are written to Susie L. Meyers Bobb, who was likely also Susie L. Raymond.Scope and Content Note: Contains letters written to and from various members of the Bobb, Raymond, and Meyers families of Illinois, Iowa, and Pennsylvania. Most of the letters are written to Susie L. Meyers, who was later Susie L. Bobb. There are also letters to a Susie L. Raymond, who is probably the same woman. Susie's sister Anna Meyers Yarger wrote a number of the letters. The letters discuss family and community life.Biographical/Historical Note: Susie L. Meyers, daughter of Reuben and Sarah Meyers, was born in 1867 in Illinois. She married Eugene Bobb around 1897 or 1898. Eugene Bobb was one of two surviving sons of Dr. Daniel and Arminda Bobb of Dakota, Illinois. Eugene's surviving brother was Dwight. Eugene had previously married Lillie Clump, who died in 1897. Susie Meyers Bobb most likely was previously married to an Austin Raymond

The St. Louis Flood: Some Observations On Warning And Pre-Impact Disaster Response

During the latter part of March continuing to the end of April 1973, three flood crests on the Mississippi River caused property damage and disruption in three counties surrounding St. Louis, Missouri and, to some extent, in the city itself. While press reports seemed to indicate that the actual impact on the city was not major, there did appear to be a mobilization of organizations in the city in preparation for and response to such an event. On the basis of press reports and other information, the Disaster Research Center (DRC) sent a two-man field team to St. Louis. The team stayed two days, May 3 and 4, concentrating on flood-associated activities in St. Louis and the three surrounding counties and attempting to get answers to the following questions: (1) If a disaster had occurred, in what way was the community response coordinated in two emergency task areas: warning and pre-impact activities.(2) What role did the local civil defense (CD) organization play in the coordination of warning and pre-impact activities; (3) Did the flood situation and/or the CD flood activities have any effect on how the community and the community organizations viewed CD's saliency and legitimacy as a viable emergency organization

Tumor gangliosides accelerate murine tumor angiogenesis

Tumor cells shed gangliosides and populate their microenvironment with these biologically active membrane glycosphingolipids. In vitro, ganglioside enrichment amplifies receptor tyrosine kinase signaling and activation of vascular endothelial cells. However, a long-standing question is whether in the actual microenvironment of a neoplasm, in vivo, tumor cell ganglioside shedding stimulates angiogenesis. Here we tested the hypothesis that tumor gangliosides have a critical proangiogenic role in vivo using novel murine tumor cells (DKO) genetically completely incapable of ganglioside synthesis and impaired in tumor growth vs. wild-type (WT) ganglioside-rich cells. We studied angiogenesis during tumor formation by these ganglioside-depleted cells, quantifying vessel formation, angiogenic factor production/release, and consequences of reconstitution with purified WT gangliosides. DKO cells formed virtually avascular tumors, much smaller than ganglioside-rich WT tumors and displaying a striking paucity of blood vessels, despite levels of VEGF and other angiogenic factors that were similar to those of WT cells. Transient enrichment of the ganglioside milieu of the DKO cell inoculum by adding purified WT gangliosides partially restored angiogenesis and tumor growth. We conclude that tumor gangliosides trigger robust angiogenesis important for tumor growth. Our findings suggest strategies to eliminate their synthesis and shedding by tumor cells should be pursued

The HSP90 inhibitor alvespimycin enhances the potency of telomerase inhibition by imetelstat in human osteosarcoma.

The unsatisfactory outcomes for osteosarcoma necessitate novel therapeutic strategies. This study evaluated the effect of the telomerase inhibitor imetelstat in pre-clinical models of human osteosarcoma. Because the chaperone molecule HSP90 facilitates the assembly of telomerase protein, the ability of the HSP90 inhibitor alvespimycin to potentiate the effect of the telomerase inhibitor was assessed. The effect of single or combined treatment with imetelstat and alvespimycin on long-term growth was assessed in osteosarcoma cell lines (143B, HOS and MG-63) and xenografts derived from 143B cells. Results indicated that imetelstat as a single agent inhibited telomerase activity, induced telomere shortening, and inhibited growth in all 3 osteosarcoma cell lines, though the bulk cell cultures did not undergo growth arrest. Combined treatment with imetelstat and alvespimycin resulted in diminished telomerase activity and shorter telomeres compared to either agent alone as well as higher levels of γH2AX and cleaved caspase-3, indicative of increased DNA damage and apoptosis. With dual telomerase and HSP90 inhibition, complete growth arrest of bulk cell cultures was achieved. In xenograft models, all 3 treatment groups significantly inhibited tumor growth compared with the placebo-treated control group, with the greatest effect seen in the combined treatment group (imetelstat, p = 0.045, alvespimycin, p = 0.034; combined treatment, p = 0.004). In conclusion, HSP90 inhibition enhanced the effect of telomerase inhibition in pre-clinical models of osteosarcoma. Dual targeting of telomerase and HSP90 warrants further investigation as a therapeutic strategy

Development of an animal model of nephrocalcinosis via selective dietary sodium and chloride depletion

Background:Nephrocalcinosis (NC) is an important clinical problem seen in critically ill preterm neonates treated with loop diuretics. No reliable animal models are available to study the pathogenesis of NC in preterm infants. The purpose of this study was to develop a reproducible and clinically relevant animal model of NC for these patients and to explore the impact of extracellular fluid (ECF) volume contraction induced by sodium and chloride depletion in this process.Methods:Three-week-old weanling Sprague-Dawley rats were fed diets deficient in either chloride or sodium or both. A subgroup of rats from each dietary group was injected daily with furosemide (40 mg/kg i.p.).Results:Rats fed a control diet, with or without furosemide, or a chloride-depleted diet alone, did not develop NC. By contrast, 50% of the rats injected with furosemide and fed the chloride-depleted diet developed NC. Moreover, 94% of the rats fed the combined sodium- and chloride-depleted diet developed NC, independently of furosemide use. NC was associated with the development of severe ECF volume contraction; hypochloremic, hypokalemic, metabolic alkalosis; increased phosphaturia; and growth retardation.Conclusion:Severe ECF volume contraction induced by chronic sodium and chloride depletion appears to play an important role in the pathogenesis of NC. Copyright © 2013 International Pediatric Research Foundation, Inc