Oxalates as Activating Groups for Alcohols in Visible Light Photoredox Catalysis: Formation of Quaternary Centers by Redox-Neutral Fragment Coupling.

Alkyl oxalates are new bench-stable alcohol-activating groups for radical generation under visible light photoredox conditions. Using these precursors, the first net redox-neutral coupling of tertiary and secondary alcohols with electron-deficient alkenes is achieved

Attenuation of hedgehog/GLI signaling by NT1721 extends survival in pancreatic cancer.

BackgroundPancreatic cancer is one of the most lethal malignancies due to frequent late diagnosis, aggressive tumor growth and metastasis formation. Continuously raising incidence rates of pancreatic cancer and a lack of significant improvement in survival rates over the past 30 years highlight the need for new therapeutic agents. Thus, new therapeutic agents and strategies are urgently needed to improve the outcome for patients with pancreatic cancer. Here, we evaluated the anti-tumor activity of a new natural product-based epidithiodiketopiperazine, NT1721, against pancreatic cancer.MethodsWe characterized the anticancer efficacy of NT1721 in multiple pancreatic cancer cell lines in vitro and in two orthotopic models. We also compared the effects of NT1721 to clinically used hedgehog inhibitors and the standard-of-care drug, gemcitabine. The effect of NT1721 on hedgehog/GLI signaling was assessed by determining the expression of GLI and GLI target genes both in vitro and in vivo.ResultsNT1721 displayed IC50 values in the submicromolar range in multiple pancreatic cancer cell lines, while largely sparing normal pancreatic epithelial cells. NT1721 attenuated hedgehog/GLI signaling through downregulation of GLI1/2 transcription factors and their downstream target genes, which reduced cell proliferation and invasion in vitro and significantly decreased tumor growth and liver metastasis in two preclinical orthotopic mouse models of pancreatic cancer. Importantly, treatment with NT1721 significantly improved survival times of mice with pancreatic cancer compared to the standard-of-care drug, gemcitabine.ConclusionsFavorable therapeutics properties, i.e. 10-fold lower IC50 values than clinically used hedgehog inhibitors (vismodegib, erismodegib), a 90% reduction in liver metastasis and significantly better survival times compared to the standard-of-care drug, gemcitabine, provide a rational for testing NT1721 in the clinic either as a single agent or possibly in combination with gemcitabine or other therapeutic agents in PDAC patients overexpressing GLI1/2. This could potentially result in promising new treatment options for patients suffering from this devastating disease

“An opportunist piece of electioneering”: experts criticise the Conservatives’ Human Rights Act repeal pledge

David Cameron recently announced his intention to repeal the Human Rights Act were his Conservative Party to be returned to Government following the General Election scheduled for May 2015. Democratic Audit asked human rights experts to contribute their assesment of the idea, particularly in light of further details of the proposal outlined by the Justice Secretary Chris Grayling. Part one can be found here

Stereoselection in the Prins-Pinacol Synthesis of Acyltetrahydrofurans

Depending upon the nature of the alkene and allylic substituents, acid-promoted rearrangements of acetals derived from anti allylic diols give 12 or stereoisomeric acyltetrahydrofurans 13. Stereoelectronic effects of the allylic substituents and the extent of bonding in the Prins cyclization transition state are central features of a proposed new model for predicting stereoselection in the Prins-pinacol synthesis of acyltetrahydrofurans

An African-American Resources and Needs Assessment of the West Bloomington Area, Phase 1

Over the course of the Fall 2009 semester, students in the Community Project Design and Management class worked with members of West Bloomington to recognize the growing needs within the community. Along with the African-American Focus Workgroup (AAFW) and the West Bloomington Revitalization Partnership (WBRP), the students completed Phase 1 of an African-American resources and needs assessment resulting in this report. This document reflects needs, wants, and hopes of the West Bloomington community and the AAFW. Comprehensively, this document is meant to serve as a bridge between community members and AAFW members. As Bloomington as a whole continues to grow and expand, some members within the community feel the difficulty of being left out of development. Therefore, the project‟s purpose was to help ascertain the assets and deficiencies within the West Bloomington neighborhood with the participation of community members, and to help the AAFW integrate their goals with those of the WBRP. This report can aid future efforts and provide useful information in the development of the West Bloomington area. The report includes a brief review of the literature considering race, education, income, age, public space, housing, civil society, and community-based participatory research. The report also includes sections outlining the research methods used, the research findings along the same themes used in the literature review, a discussion of limitations and barriers to research, and conclusions and recommendations. Appendices include Institutional Review Board (IRB) protocol for ethical treatment and protection of research participants, definition of the study area for drawing out Census data, and a Survey Design and Administration Protocol Handbook to aid in administering surveys drafted for AAFW member organizations to use with their staff and volunteers, patrons, and the general public. Student researchers analyzed public data and local reports to understand the background and demographics of the West Bloomington community. Reports consulted include these topics: housing conditions and issues; food justice; Census data on race, income, and age; community and economic development; and education statistics for District 87 and West Bloomington schools. Through various focus groups, four common themes appeared: the need for greater communication between and among local organizations and community members; the need for additional activities, especially for young people; a lack of accessibility to various services offered by (or in) the City of Bloomington and surrounding areas; and distressed amenities. Communication can be strengthened between the WBRP and the AAFW, between West Bloomington community members and the City of Bloomington, and among all of these groups and members. Focus group findings also show that the West Bloomington community and organizations serving it do not offer activities to people of all age ranges. In addition, all focus groups shared comments about transportation issues within West Bloomington. Regarding distressed amenities, focus group participants brought up issues concerning poor housing conditions, inadequate amenities at local parks, and old infrastructure in need of repair or replacement. Findings from key informant interviews also acknowledged several areas for enhancement within the West Bloomington community. Within the community, apathy and a lack of respect among residents were identified as negative attributes coupled with a perceived lack of police presence in the area. Residents linked these attributes to a fear of crime, and specifically, drug dealing, prostitution, and gang activity and recruitment. Resource collaboration and greater awareness of available resources also are viewed as necessary enhancements within the community and those serving it. West Bloomington residents serving as key informant interviewees identified issues of homelessness, overcrowded housing facilities, and a lack of affordable housing. Some interviewees expressed a desire for better notification of neighborhood events. Several interviewees mentioned a desire for better communication between the City of Bloomington and West Bloomington community and a better working relationship with the police department. Additionally, multiple interviewees discussed the importance of education, including the need for more job training and literacy programs. This report includes conclusions and recommendations based on findings from key informant interviews, focus groups, local and public data review, and past and future surveys. These recommendations are broken down into three categories focusing on the City of Bloomington, the West Bloomington neighborhood, and youth. City-related recommendations include the following: The Bloomington Police Department can increase its visible presence in the West Bloomington neighborhood by providing foot patrol. The City of Bloomington should develop a plan for addressing infrastructure needs in the West Bloomington area. The Bloomington-Normal Public Transit System can evaluate the current mass transit bus routes for West Bloomington. Improved civic awareness and education can increase residents‟ skills and abilities to address grievances and development issues within their community. Neighborhood recommendations advise the following: Primarily, communication among all stakeholders needs to be improved. Stakeholders can increase awareness of available services, programs, and resources that can benefit community members. A community fair can be held within the West Bloomington neighborhood. A feasibility study should be performed for a multi-purpose community center to be located in the West Bloomington neighborhood. The youth recommendations suggest the following: Encourage The Bloomington Boys and Girls Club to determine if additional services could be added to benefit the teen youth of West Bloomington. Increase the availability of summer programs to benefit both working parents and children. Explore effective strategies for identifying and dealing with barriers to development, especially those that apply to youth and crime. Stakeholders can collaborate on a campaign to bring awareness and encourage action around the need for more volunteer mentors, especially male mentors who are needed for West Bloomington male youth. In conclusion, this report sheds some light on the needs, wants, assets, and resources of the West Bloomington community. It is our hope that this report will serve as an impetus for enhanced relationships among the AAFW, the WBRP, West Bloomington residents, and the City of Bloomington, as well as provide information and materials to aid in future development

Canvass: a crowd-sourced, natural-product screening library for exploring biological space

NCATS thanks Dingyin Tao for assistance with compound characterization. This research was supported by the Intramural Research Program of the National Center for Advancing Translational Sciences, National Institutes of Health (NIH). R.B.A. acknowledges support from NSF (CHE-1665145) and NIH (GM126221). M.K.B. acknowledges support from NIH (5R01GM110131). N.Z.B. thanks support from NIGMS, NIH (R01GM114061). J.K.C. acknowledges support from NSF (CHE-1665331). J.C. acknowledges support from the Fogarty International Center, NIH (TW009872). P.A.C. acknowledges support from the National Cancer Institute (NCI), NIH (R01 CA158275), and the NIH/National Institute of Aging (P01 AG012411). N.K.G. acknowledges support from NSF (CHE-1464898). B.C.G. thanks the support of NSF (RUI: 213569), the Camille and Henry Dreyfus Foundation, and the Arnold and Mabel Beckman Foundation. C.C.H. thanks the start-up funds from the Scripps Institution of Oceanography for support. J.N.J. acknowledges support from NIH (GM 063557, GM 084333). A.D.K. thanks the support from NCI, NIH (P01CA125066). D.G.I.K. acknowledges support from the National Center for Complementary and Integrative Health (1 R01 AT008088) and the Fogarty International Center, NIH (U01 TW00313), and gratefully acknowledges courtesies extended by the Government of Madagascar (Ministere des Eaux et Forets). O.K. thanks NIH (R01GM071779) for financial support. T.J.M. acknowledges support from NIH (GM116952). S.M. acknowledges support from NIH (DA045884-01, DA046487-01, AA026949-01), the Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Medical Research Program (W81XWH-17-1-0256), and NCI, NIH, through a Cancer Center Support Grant (P30 CA008748). K.N.M. thanks the California Department of Food and Agriculture Pierce's Disease and Glassy Winged Sharpshooter Board for support. B.T.M. thanks Michael Mullowney for his contribution in the isolation, elucidation, and submission of the compounds in this work. P.N. acknowledges support from NIH (R01 GM111476). L.E.O. acknowledges support from NIH (R01-HL25854, R01-GM30859, R0-1-NS-12389). L.E.B., J.K.S., and J.A.P. thank the NIH (R35 GM-118173, R24 GM-111625) for research support. F.R. thanks the American Lebanese Syrian Associated Charities (ALSAC) for financial support. I.S. thanks the University of Oklahoma Startup funds for support. J.T.S. acknowledges support from ACS PRF (53767-ND1) and NSF (CHE-1414298), and thanks Drs. Kellan N. Lamb and Michael J. Di Maso for their synthetic contribution. B.S. acknowledges support from NIH (CA78747, CA106150, GM114353, GM115575). W.S. acknowledges support from NIGMS, NIH (R15GM116032, P30 GM103450), and thanks the University of Arkansas for startup funds and the Arkansas Biosciences Institute (ABI) for seed money. C.R.J.S. acknowledges support from NIH (R01GM121656). D.S.T. thanks the support of NIH (T32 CA062948-Gudas) and PhRMA Foundation to A.L.V., NIH (P41 GM076267) to D.S.T., and CCSG NIH (P30 CA008748) to C.B. Thompson. R.E.T. acknowledges support from NIGMS, NIH (GM129465). R.J.T. thanks the American Cancer Society (RSG-12-253-01-CDD) and NSF (CHE1361173) for support. D.A.V. thanks the Camille and Henry Dreyfus Foundation, the National Science Foundation (CHE-0353662, CHE-1005253, and CHE-1725142), the Beckman Foundation, the Sherman Fairchild Foundation, the John Stauffer Charitable Trust, and the Christian Scholars Foundation for support. J.W. acknowledges support from the American Cancer Society through the Research Scholar Grant (RSG-13-011-01-CDD). W.M.W.acknowledges support from NIGMS, NIH (GM119426), and NSF (CHE1755698). A.Z. acknowledges support from NSF (CHE-1463819). (Intramural Research Program of the National Center for Advancing Translational Sciences, National Institutes of Health (NIH); CHE-1665145 - NSF; CHE-1665331 - NSF; CHE-1464898 - NSF; RUI: 213569 - NSF; CHE-1414298 - NSF; CHE1361173 - NSF; CHE1755698 - NSF; CHE-1463819 - NSF; GM126221 - NIH; 5R01GM110131 - NIH; GM 063557 - NIH; GM 084333 - NIH; R01GM071779 - NIH; GM116952 - NIH; DA045884-01 - NIH; DA046487-01 - NIH; AA026949-01 - NIH; R01 GM111476 - NIH; R01-HL25854 - NIH; R01-GM30859 - NIH; R0-1-NS-12389 - NIH; R35 GM-118173 - NIH; R24 GM-111625 - NIH; CA78747 - NIH; CA106150 - NIH; GM114353 - NIH; GM115575 - NIH; R01GM121656 - NIH; T32 CA062948-Gudas - NIH; P41 GM076267 - NIH; R01GM114061 - NIGMS, NIH; R15GM116032 - NIGMS, NIH; P30 GM103450 - NIGMS, NIH; GM129465 - NIGMS, NIH; GM119426 - NIGMS, NIH; TW009872 - Fogarty International Center, NIH; U01 TW00313 - Fogarty International Center, NIH; R01 CA158275 - National Cancer Institute (NCI), NIH; P01 AG012411 - NIH/National Institute of Aging; Camille and Henry Dreyfus Foundation; Arnold and Mabel Beckman Foundation; Scripps Institution of Oceanography; P01CA125066 - NCI, NIH; 1 R01 AT008088 - National Center for Complementary and Integrative Health; W81XWH-17-1-0256 - Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Medical Research Program; P30 CA008748 - NCI, NIH, through a Cancer Center Support Grant; California Department of Food and Agriculture Pierce's Disease and Glassy Winged Sharpshooter Board; American Lebanese Syrian Associated Charities (ALSAC); University of Oklahoma Startup funds; 53767-ND1 - ACS PRF; PhRMA Foundation; P30 CA008748 - CCSG NIH; RSG-12-253-01-CDD - American Cancer Society; RSG-13-011-01-CDD - American Cancer Society; CHE-0353662 - National Science Foundation; CHE-1005253 - National Science Foundation; CHE-1725142 - National Science Foundation; Beckman Foundation; Sherman Fairchild Foundation; John Stauffer Charitable Trust; Christian Scholars Foundation)Published versionSupporting documentatio

Cellular Based Aggregated Satellite System: The Design and Architecture of a Three Degree of Freedom Near-Frictionless Testbed for Ground Validation of CubeSat Operations

As small and nano-satellite operations become more complex and increase in functionality, the need to validate new concepts prior to deployment in a low-cost and time efficient manner has further increased. While computer simulations have traditionally provided acceptable results for guidance navigation and control (GNC) algorithms, more complex actions such as rendezvous and proximity operations and docking (RPOD) require alternative methods, which often require ground-based platforms. The concept of on-orbit autonomous docking of small satellites has grown in popularity due to its broad range of applications. However, most existing ground testing platforms (GTP) are expensive due to the technologies used and large physical space required. Due to the importance of RPOD to nano-satellites specifically, the development of a low-profile GTP is a crucial component in the testing and validation of small satellite concepts. The Space Engineering Research Center (SERC) at the University of Southern California (USC) has designed and manufactured a GTP capable of validating various unique nano-satellite operations in a cost-effective and space-efficient manner. This paper will focus on the design and architecture of a three degree of freedom (3DoF) near-frictionless testbed for ground validation of RPOD in a microgravity environment and its use with various small satellite applications

Peningkatan Prestasi Belajar CAD Mahasiswa Teknik Otomotif Non-Reguler FT UNY melalui Pembuatan “Pohon Kata” Perintah dalam Program AutoCAD

Penelitian ini bertujuan meningkatkan prestasi belajar mata kuliah Computer Aided Design (CAD) mahasiswa prodi Teknik Otomotif Non-Reguler yang dinyatakan dalam bentuk rerata nilai akhir semester yang berasal dari komponen nilai tugas harian, nilai ujian tengah semester dan nilai ujian akhir semester. Penelitian quasi-eksperimen ini terdiri dari tahapan penelitian diawali dengan penyusunan materi pembelajaran sejumlah pokok bahasan tertentu dalam satu job sheet (lembar kerja), dilanjutkan dengan pembuatan bantuan “Pohon Kata” perintah dalam Auto CAD kepada kelas eksperimen yang ditentukan secara random dari dua kelas peserta kuliah Auto CAD pada Semester Genap 2008/2009. Kedua kelas diamati prestasinya, baik kecepatan penyelesaiannya maupun kualitas kebenaran gambarnya. Prestasi belajar kedua kelas juga diukur melalui pemberian ujian tengah semester dan ujian akhir semester. Setelah data prestasi kedua kelas terkumpul dilanjutkan dengan analisis statistik melalui uji beda (t-test) setelah sebelumnya dilakukan uji persyaratan analisis yang ternyata dapat dipenuhi. Hasil penelitian ini disimpulkan bahwa: prestasi belajar CAD mahasiswa pada kelas yang diberi perlakuan strategi pembelajaran menggunakan “Pohon Kata” perintah dalam Program Auto CAD lebih baik dibanding prestasi belajar CAD mahasiswa pada kelas yang tidak diberi perlakuan (75,41>70,89), dengan demikian pembelajaran CAD menggunakan media “Pohon Kata” perintah dalam Program Auto CAD dapat meningkatkan prestasi belajar mahasiswa Teknik Otomotif Program Non-Reguler

Oxalates as Activating Groups for Alcohols in Visible Light Photoredox Catalysis: Formation of Quaternary Centers by Redox-Neutral Fragment Coupling.

Alkyl oxalates are new bench-stable alcohol-activating groups for radical generation under visible light photoredox conditions. Using these precursors, the first net redox-neutral coupling of tertiary and secondary alcohols with electron-deficient alkenes is achieved