251 research outputs found
Constructive Noncooperation: Living in Truth
Mohandas Gandhi often indicated that nonviolence was “a science,” and he appears to have meant this literally. Consistent with this vision, in this paper, we outline and apply principles of behavioral systems science, an emerging data-based approach to understanding the dynamics of complex cultural systems, to the practice of constructive noncooperation (Gandhi’s “constructive programme”). Although Gandhi emphasized that constructive action was the most important and potent of nonviolent strategic options, constructive alternatives have been the least developed in the literature of nonviolent struggle. The reconceptualization of constructive noncooperation in behavioral systems terms offered here suggests that rigorous analysis of Havel’s “living in truth” and Gandhi’s “truth force” may be both possible and practically useful in challenging oppression and supporting human rights
La peinture ne recouvre pas notre précarité
[animation:peintureprecarite] La peinture ne recouvre pas notre précarité apparaît avec le désir de créer une réflexion non seulement autour des grèves et des luttes qui ont eu lieu en France dès décembre 2019, mais aussi avec la volonté de se demander quelle est la place de la communauté universitaire dans ces mouvements. En prenant des photographies de manifestations parisiennes mais aussi de graffitis, collages, affiches et même de traces d’inscriptions grévistes partout en France, j’ai co..
Farmers Markets and the Local Food System: The Case of Gettysburg, Pennsylvania
In order to examine and obtain a better understanding of the local food system within Adams County, Pennsylvania, this study explores the characteristics and perspectives of the customers and vendors at the farmers markets in Gettysburg, Pennsylvania. Survey findings from the Gettysburg Farmers Market and the three Adams County Farmers Markets include customer demographic information, perspectives and shopping behavior as well as vendor product information, farm size and location and preference for market management. Introductory background information on the Farm Bill and the influence of agricultural practices on the environment, human health and nutrition and the relationship between farmers markets and the local economy are offered in order to emphasize the value of a well-managed local food system. Conclusions provide evidence that lower income and lower education levels are not sufficiently represented at all the markets and food stamp programs are being underutilized. This study suggests employing additional marketing to target underrepresented demographic groups, public transportation to potentially inaccessible market locations and increased advertisement and encouragement of food stamp programs at all markets in order to expand the customer base and increase access to healthy, local foods for less advantaged citizens. The results from this study are intended to offer evidence that will promote and facilitate market management, strengthen customer/vendor relationships and encourage better ties between the local community and local food systems at the farmers markets within Gettysburg in Adams County, Pennsylvania
An epitope tag alters phosphoglycerate dehydrogenase structure and impairs ability to support cell proliferation
Background
The gene encoding the serine biosynthesis pathway enzyme PHGDH is located in a region of focal genomic copy number gain in human cancers. Cells with PHGDH amplification are dependent on enzyme expression for proliferation. However, dependence on increased PHGDH expression extends beyond production of serine alone, and further studies of PHGDH function are necessary to elucidate its role in cancer cells. These studies will require a physiologically relevant form of the enzyme for experiments using engineered cell lines and recombinant protein.
Results
The addition of an N-terminal epitope tag to PHGDH abolished the ability to support proliferation of PHGDH-amplified cells despite retention of some activity to convert 3-PG to PHP. Introducing an R236E mutation into PHGDH eliminates enzyme activity, and this catalytically inactive enzyme cannot support proliferation of PHGDH-dependent cells, arguing that canonical enzyme activity is required. Tagged and untagged PHGDH exhibit the same intracellular localization and ability to produce D-2-hydroxyglutarate (D-2HG), an error product of PHGDH, arguing that neither mislocalization nor loss of D-2HG production explains the inability of epitope-tagged PHGDH to support proliferation. To enable studies of PHGDH function, we report a method to purify recombinant PHGDH and found that untagged enzyme activity was greater than N-terminally tagged enzyme. Analysis of tagged and untagged PHGDH using size exclusion chromatography and electron microscopy found that an N-terminal epitope tag alters enzyme structure.
Conclusions
Purification of untagged recombinant PHGDH eliminates the need to use an epitope tag for enzyme studies. Furthermore, while tagged PHGDH retains some ability to convert 3PG to PHP, the structural alterations caused by including an epitope tag disrupts the ability of PHGDH to sustain cancer cell proliferation.National Science Foundation (U.S.). Graduate Research Fellowship (DGE-1122374)T32GM007287National Cancer Institute (U.S.) (R01CA168653)National Cancer Institute (U.S.) (P30CA14051)Burroughs Wellcome FundAmerican Association for Cancer Researc
Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis
Cancer cells engage in a metabolic program to enhance biosynthesis and support cell proliferation. The regulatory properties of pyruvate kinase M2 (PKM2) influence altered glucose metabolism in cancer. The interaction of PKM2 with phosphotyrosine-containing proteins inhibits enzyme activity and increases the availability of glycolytic metabolites to support cell proliferation. This suggests that high pyruvate kinase activity may suppress tumor growth. We show that expression of PKM1, the pyruvate kinase isoform with high constitutive activity, or exposure to published small-molecule PKM2 activators inhibits the growth of xenograft tumors. Structural studies reveal that small-molecule activators bind PKM2 at the subunit interaction interface, a site that is distinct from that of the endogenous activator fructose-1,6-bisphosphate (FBP). However, unlike FBP, binding of activators to PKM2 promotes a constitutively active enzyme state that is resistant to inhibition by tyrosine-phosphorylated proteins. These data support the notion that small-molecule activation of PKM2 can interfere with anabolic metabolism.National Institutes of Health (U.S.) (NIH grant R01 GM56203)National Institutes of Health (U.S.) (grant NIH 5P01CA120964)Dana-Farber/Harvard Cancer Center (NIH 5P30CA006516)National Institutes of Health (U.S.) (NIH grant R03MH085679)National Human Genome Research Institute (U.S.) (Intramural Research Program)National Institutes of Health (U.S.) (Molecular Libraries Initiative of the NIH Roadmap for Medical Research
The VLT-VIRMOS Mask Manufacturing Unit
The VIRMOS Consortium has the task to design and manufacture two
spectrographs for ESO VLT, VIMOS (Visible Multi-Object Spectrograph) and NIRMOS
(Near Infrared Multi-Object Spectrograph). This paper describes how the Mask
Manufacturing Unit (MMU), which cuts the slit masks to be used with both
instruments, meets the scientific requirements and manages the storage and the
insertion of the masks into the instrument. The components and the software of
the two main parts of the MMU, the Mask Manufacturing Machine and the Mask
Handling System, are illustrated together with the mask material and with the
slit properties. Slit positioning is accurate within 15 micron, equivalent to
0.03 arcsec on the sky, while the slit edge roughness has an rms on the order
of 0.03 pixels on scales of a slit 5 arcsec long and of 0.01 pixels on the
pixel scale (0.205 arcsec). The MMU has been successfully installed during
July/August 2000 at the Paranal Observatory and is now operational for
spectroscopic mask cutting, compliant with the requested specifications.Comment: Accepted for publication in PASP April 2001 PASP Latex preprint
style, 31 pages including 9 figures (5 jpg2eps compressed
One-carbon metabolism in cancer
Cells require one-carbon units for nucleotide synthesis, methylation and reductive metabolism, and these pathways support the high proliferative rate of cancer cells. As such, anti-folates, drugs that target one-carbon metabolism, have long been used in the treatment of cancer. Amino acids, such as serine are a major one-carbon source, and cancer cells are particularly susceptible to deprivation of one-carbon units by serine restriction or inhibition of de novo serine synthesis. Recent work has also begun to decipher the specific pathways and sub-cellular compartments that are important for one-carbon metabolism in cancer cells. In this review we summarise the historical understanding of one-carbon metabolism in cancer, describe the recent findings regarding the generation and usage of one-carbon units and explore possible future therapeutics that could exploit the dependency of cancer cells on one-carbon metabolism
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