Cracking the Network Code: Four Principles for Grantmakers

As grantmakers and nonprofits are looking for ways to collaborate more effectively, many are experimenting working with and through networks to achieve greater impact. Because networks are by definition loosely controlled and emergent, understanding how to effectively support them feels like a mystery to many grantmakers.GEO's newest publication sets out to crack the code behind the network mystique. In fact, there is a method to working more efficiently and effectively through networks, and a critical first step for grantmakers is adopting a network mindset, which may require dramatic shifts in attitude and behavior for some. "Cracking the Network Code" outlines four principles that comprise the network mindset, illustrates the principles with a range of examples of networks that have achieved real results, and offers practical questions and recommendations to help grantmakers achieve the benefits and avoid common pitfalls of working through networks

Retrovirus-delivered siRNA

BACKGROUND: The ability of transfected synthetic small interfering (si) RNAs to suppress the expression of specific transcripts has proved a useful technique to probe gene function in mammalian cells. However, high production costs limit this technology's utility for many laboratories and experimental situations. Recently, several DNA-based plasmid vectors have been developed that direct transcription of small hairpin RNAs, which are processed into functional siRNAs by cellular enzymes. Although these vectors provide certain advantages over chemically synthesized siRNAs, numerous disadvantages remain including merely transient siRNA expression and low and variable transfection efficiency. RESULTS: To overcome several limitations of plasmid-based siRNA, a retroviral siRNA delivery system was developed based on commerically available vectors. As a pilot study, a vector was designed to target the human Nuclear Dbf2-Related (NDR) kinase. Cells infected with the anti-NDR siRNA virus dramatically downregulate NDR expression, whereas control viruses have no effect on total NDR levels. To confirm and extend these findings, an additional virus was constructed to target a second gene, transcriptional coactivator p75. CONCLUSION: The experiments presented here demonstrate that retroviruses are efficient vectors for delivery of siRNA into mammalian cells. Retrovirus-delivered siRNA provides significant advancement over previously available methods by providing efficient, uniform delivery and immediate selection of stable "knock-down" cells. This development should provide a method to rapidly assess gene function in established cell lines, primary cells, or animals

Micro-Calorimeters with NTD and Epitaxial Germanium Thermistors for High Resolution X-Ray Spectroscopy

This is a progress report for the third year of a three year SR&T grant to continue the advancement of NTD-based microcalorimeters. We highlight our progress to date that allowed us to garner an additional three years of funding for this work

Geologic setting and lithologic column of the Cajon Pass Deep Drillhole

The Cajon Pass Deep Drillhole penetrates a late Tertiary basin developed on crystalline basement in the SW Mojave Desert, 4 km from the San Andreas fault. Cores, continuous cuttings and geophysical logs from phase I show great diversity in rock types, structure, and alteration. The hole encountered Cajon formation arkoses; granodiorite/tonalite; unusual megacrystic granite and augen gneiss; granitic and pelitic gneisses with quartzite; quartzofeldspathic orthogneiss cut by sheets of hornblende gabbro; and interlayered mafic and quartzofeldspathic orthogneisses with rare calcsilicate intervals. Foliation and compositional layering have low dips throughout the column and layered gneisses contain 10-cm-scale recumbent folds. Faults and alteration zones bound several rock units with low apparent dips. Basement cores are typically cut by steep fractures, <1 mm wide, that contain zeolites±calcite or chlorite-epidote. Fractures and faults decrease in abundance with depth

Lithologic column of the “Arkoma” Drillhole and its relation to the Cajon Pass Deep Drillhole

The 1795 m "Arkoma" Federal 1-26 well, 48.5 m from the Cajon Pass Deep Drillhole (CPDDH), provides additional lithologic and structural data pertinent to that project. Basement surface was encountered 158 m deeper than in the CPDDH. Rock units correlate well between the holes; the offset persists to 1128 m. Below this depth both lithologic unit thicknesses and fault zones correlate between holes on subhorizontal projections. A combination of previously unrecognized high-angle and low-angle faults of several ages are required to explain the structures. Blind low angle faults may be regionally important

Implications of zeolites and their zonation in the Cajon Pass Deep Drillhole

Zeolites occur in all cores and most cuttings samples of plutonic and gneissic rock from the Cajon Pass Deep Drillhole. Laumontite or stilbite replace plagioclase and fill fractures <1 mm to several cms in width. Zeolitic alteration is most intense in faulted and fractured zones. Zeolite species are zoned vertically. Laumontite occurs to a depth of 1885 m, stilbite from 1885 m to 2080 m and laumontite again to at least 2524 m. The transition from stilbite to laumontite at 2080 m fits both extrapolated equilibria and the CPDDH P-T gradient but laumontite occurrences above 1885 m are metastable apparently reflecting rapid uplift. Radioactive accessory minerals from the wall rock surrounded by zeolites in some fractures exhibit red-brown haloes. Halo intensity correlates to mineral radioactivity and may allow dating of mineraliztion. Observation in the CPDDH suggest a potential role for zeolites in determining chemical and physical properties such as pore water composition, seismic velocity, and gravity contrasts in faults of the San Andreas system

HIV-1 incorporates and proteolytically processes human NDR1 and NDR2 serine-threonine kinases

AbstractMammalian genomes encode two related serine-threonine kinases, nuclear Dbf2 related (NDR)1 and NDR2, which are homologous to the Saccharomyces cerevisiae Dbf2 kinase. Recently, a yeast genetic screen implicated the Dbf2 kinase in Ty1 retrotransposition. Since several virion-incorporated kinases regulate the infectivity of human immunodeficiency virus type 1 (HIV-1), we speculated that the human NDR1 and NDR2 kinases might play a role in the HIV-1 life cycle. Here we show that the NDR1 and NDR2 kinases were incorporated into HIV-1 particles. Furthermore, NDR1 and NDR2 were cleaved by the HIV-1 protease (PR), both within virions and within producer cells. Truncation at the PR cleavage site altered NDR2 subcellular localization and inhibited NDR1 and NDR2 enzymatic activity. These studies identify two new virion-associated host cell enzymes and suggest a novel mechanism by which HIV-1 alters the intracellular environment of human cells

Report of the sensor readout electronics panel

The findings of the Sensor Readout Electronics Panel are summarized in regard to technology assessment and recommended development plans. In addition to two specific readout issues, cryogenic readouts and sub-electron noise, the panel considered three advanced technology areas that impact the ability to achieve large format sensor arrays. These are mega-pixel focal plane packaging issues, focal plane to data processing module interfaces, and event driven readout architectures. Development in each of these five areas was judged to have significant impact in enabling the sensor performance desired for the Astrotech 21 mission set. Other readout issues, such as focal plane signal processing or other high volume data acquisition applications important for Eos-type mapping, were determined not to be relevant for astrophysics science goals

Petrological and geochemical investigations at the Cajon Pass Deep Drillhole

Chemical analyses of cores from the Cajon Pass Deep Drillhole confirm vertical lithologic diversity of the basement rocks. They are metaluminous and calcalkaline; weak major element correlations with wide-ranging SiO_2 suggest they are not a simple cogenetic suite. Quartz contents correlate with the thermal gradient profile, supporting conduction as the principal thermal transport mechanism. Abundances of heat producing elements are variable and somewhat lower than average crustal values. Cross-calibration with other measures of Th, U and K are underway. Ages of surface granitoids and core 17 are late Cretaceous; other plutonic rocks appear older but late Mesozoic. Initial lead isotopic signatures of the plutonic rocks change dramatically with depth in the hole