Nickel-catalyzed reductive coupling reactions of 1,6-enynes and the total synthesis of (+)-acutiphycin

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2007.Vita.Includes bibliographical references.Nickel-Catalyzed Reductive Coupling Reactions of Aldehydes and Chiral 1,6-Enynes. A study of nickel-catalyzed reductive coupling reactions of aldehydes and chiral 1,6-enynes has provided evidence for stereospecific ligand substitution from a planar three-coordinate nickel species as a plausible explanation of regioselectivity in the nickel-catalyzed reductive coupling of aldehydes and 1,6-enynes. In the absence of a phosphine additive, high regioselectivity and high diastereoselectivity are obtained as a direct result of coordination of both the alkyne and the olefin to the metal center during the C-C bond-forming step. ... Total Synthesis of (+)-Acutiphycin. Synthetic studies toward the total synthesis of (+)-acutiphycin led to, and were in turn further developed by, the study of nickel-catalyzed reductive coupling reactions of 1,6-enynes and aldehydes. ... Ultimately, though not employing the nickel-catalyzed reaction, a highly convergent total synthesis of (+)-acutiphycin featuring an intermolecular SmI2-mediated Reformatsky coupling reaction and macrolactonization initiated by a retro-ene reaction of an alkoxyalkyne was developed. The resulting synthesis was 18 steps in the longest linear sequence from either methyl acetoacetate or isobutyraldehyde. ...by Ryan Thomas McLeod Moslin.Ph.D

Spatial and seasonal ionospheric error growth in DGPS measurement: a case study in Malaysia

This paper tackles the Equatorial ionosphere and its effects on Differential Global Positioning System (DGPS) error growth over Malaysia by using a network of GPS Continuously Operating Reference Stations (CORS). Seasonal variation of ionospheric delay has been examined and findings show that the effect of spatial variation of ionospheric errors in DGPS is very significant during the equinoctial seasons. Furthermore, a DGPS regression model was developed and tested during the solar maximum year in 2013 by using internet-based DGPS. The results show that the model is capable of estimating DGPS positional errors for distances of user to reference station less than 680 km

Regioselective Nickel-Catalyzed Reductive Couplings of Enones and Allenes

No AbstractPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78305/1/anie_201004740_sm_miscellaneous_information.pd

Nivolumab Plus Ipilimumab Versus EXTREME Regimen as First-Line Treatment for Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck: The Final Results of CheckMate 651.

Purpose: CheckMate 651 (ClinicalTrials.gov identifier: NCT02741570) evaluated first-line nivolumab plus ipilimumab versus EXTREME (cetuximab plus cisplatin/carboplatin plus fluorouracil ≤ six cycles, then cetuximab maintenance) in recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). Methods: Patients without prior systemic therapy for R/M SCCHN were randomly assigned 1:1 to nivolumab plus ipilimumab or EXTREME. Primary end points were overall survival (OS) in the all randomly assigned and programmed death-ligand 1 combined positive score (CPS) ≥ 20 populations. Secondary end points included OS in the programmed death-ligand 1 CPS ≥ 1 population, and progression-free survival, objective response rate, and duration of response in the all randomly assigned and CPS ≥ 20 populations. Results: Among 947 patients randomly assigned, 38.3% had CPS ≥ 20. There were no statistically significant differences in OS with nivolumab plus ipilimumab versus EXTREME in the all randomly assigned (median: 13.9 v 13.5 months; hazard ratio [HR], 0.95; 97.9% CI, 0.80 to 1.13; P = .4951) and CPS ≥ 20 (median: 17.6 v 14.6 months; HR, 0.78; 97.51% CI, 0.59 to 1.03; P = .0469) populations. In patients with CPS ≥ 1, the median OS was 15.7 versus 13.2 months (HR, 0.82; 95% CI, 0.69 to 0.97). Among patients with CPS ≥ 20, the median progression-free survival was 5.4 months (nivolumab plus ipilimumab) versus 7.0 months (EXTREME), objective response rate was 34.1% versus 36.0%, and median duration of response was 32.6 versus 7.0 months. Grade 3/4 treatment-related adverse events occurred in 28.2% of patients treated with nivolumab plus ipilimumab versus 70.7% treated with EXTREME. Conclusion: CheckMate 651 did not meet its primary end points of OS in the all randomly assigned or CPS ≥ 20 populations. Nivolumab plus ipilimumab showed a favorable safety profile compared with EXTREME. There continues to be a need for new therapies in patients with R/M SCCHN

Differential treatment in child guidance case work : an analysis of case work treatment methods in work with 40 mothers of pre-school children with behavior problems, Vancouver Child Guidance Clinic, 1950

In this study, emphasis has been placed on the fact that case work treatment with mothers depends upon the mother's personality. The analysis is made from 40 case records of mothers of pre-school children who were, because of problems of one sort or another, treated at the Child Guidance Clinic at Vancouver in 1950. The study analyzes case records for the above group of mothers, and it was noted that the mothers could be classified according to their personality type and a four-way classification is derived. The classification of the four groups is based upon the degree of adequacy of the mothers in terms of such factors as feelings of worth, security, self-confidence and several others. The mothers are described as "better than average", "average", "less than average", and "incomplete information". The latter group represents those mothers who were seen only once, and therefore, insufficient material is available to classify them according to the "adequacy rating" criteria. Mothers who were "better than average" were found to benefit most from treatment. The "less than average" mothers benefitted least. Treatment methods have been described descriptively. This study has employed the classification of treatment methods as derived by Mr. Geoffrey Glover in a previous study of a similar nature. Deviations from Mr. Glover's classification system are noted in the text of the study. Statistics are presented to show with what frequency the individual methods are employed by the social worker. The emphasis of the study is upon the way the mother's personality influences the worker's choice of treatment methods. It is noted that treatment in general falls into different, but over lapping phases. About 90 per cent of the treatment is found to be of a supportive nature, and 10 per cent of a more intensive kind. Mothers received more interviews than children, 58 per cent and 31 per cent respectively. Fathers received only 11 per cent of the interviews. A suggestion is made that additional training may be necessary if workers are to work on more intensive levels and to meet their accepted responsibility in treating very severely disturbed and upset clients.Arts, Faculty ofSocial Work, School ofGraduat