Star Formation and Gas Kinematics of Quasar Host Galaxies at z~6: New insights from ALMA

We present ALMA observations of the [C II] 158 micron fine structure line and dust continuum emission from the host galaxies of five redshift 6 quasars. We also report complementary observations of 250 GHz dust continuum and CO (6-5) line emission from the z=6.00 quasar SDSS J231038.88+185519.7. The ALMA observations were carried out in the extended array at 0.7" resolution. We have detected the line and dust continuum in all five objects. The derived [C II] line luminosities are 1.6x10^{9} to 8.8x10^{9} Lsun and the [C II]-to-FIR luminosity ratios are 3.0-5.6x10^{-4}, which is comparable to the values found in other high-redshift quasar-starburst systems and local ultra-luminous infrared galaxies. The sources are marginally resolved and the intrinsic source sizes (major axis FWHM) are constrained to be 0.3" to 0.6" (i.e., 1.7 to 3.5 kpc) for the [C II] line emission and 0.2" to 0.4" (i.e., 1.2 to 2.3 kpc) for the continuum. These measurements indicate that there is vigorous star formation over the central few kpc in the quasar host galaxies. The ALMA observations also constrain the dynamical properties of the atomic gas in the starburst nuclei. The intensity-weighted velocity maps of three sources show clear velocity gradients. Such velocity gradients are consistent with a rotating, gravitationally bound gas component, although they are not uniquely interpreted as such. Under the simplifying assumption of rotation, the implied dynamical masses within the [C II]-emitting regions are of order 10^{10} to 10^{11} Msun. Given these estimates, the mass ratios between the SMBHs and the spheroidal bulge are an order of magnitude higher than the mean value found in local spheroidal galaxies, which is in agreement with results from previous CO observations of high redshift quasars.Comment: 25 pages, 5 figures, accepted for publication in Ap

Submillimetre surveys: The prospects for Herschel

Using the observed submillimetre source counts, from 250-1200 microns (including the most recent 250, 350 and 500 micron counts from BLAST), we present a model capable of reproducing these results, which is used as a basis to make predictions for upcoming surveys with the SPIRE instrument aboard the Herschel Space Observatory. The model successfully fits both the integral and differential source counts of submillimetre galaxies in all wavebands, predicting that while ultra-luminous infrared galaxies dominate at the brightest flux densities, the bulk of the infrared background is due to the less luminous infrared galaxy population. The model also predicts confusion limits and contributions to the cosmic infrared background that are consistent with the BLAST results. Applying this to SPIRE gives predicted source confusion limits of 19.4, 20.5 and 16.1mJy in the 250, 350 and 500 micron bands respectively. This means the SPIRE surveys should achieve sensitivities 1.5 times deeper than BLAST, revealing a fainter population of infrared-luminous galaxies, and detecting approximately 2600, 1300, and 700 sources per square degree in the SPIRE bands (with one in three sources expected to be a high redshift ultra-luminous source at 500 microns). The model number redshift distributions predict a bimodal distribution of local quiescent galaxies and a high redshift peak corresponding to strongly evolving star-forming galaxies. It suggests the very deepest surveys with Herschel-SPIRE ought to sample the source population responsible for the bulk of the infrared background.Comment: 5 pages, 4 figures, accepted for publication in MNRAS Letter

Separation of Anti-Proliferation and Anti-Apoptotic Functions of Retinoblastoma Protein through Targeted Mutations of Its A/B Domain

BACKGROUND: The human retinoblastoma susceptibility gene encodes a nuclear phosphoprotein RB, which is a negative regulator of cell proliferation. The growth suppression function of RB requires an evolutionarily conserved A/B domain that contains two distinct peptide-binding pockets. At the A/B interface is a binding site for the C-terminal trans-activation domain of E2F. Within the B-domain is a binding site for proteins containing the LxCxE peptide motif. METHODOLOGY/PRINCIPLE FINDINGS: Based on the crystal structure of the A/B domain, we have constructed an RB-K530A/N757F (KN) mutant to disrupt the E2F- and LxCxE-binding pockets. The RB-K530A (K) mutant is sufficient to inactivate the E2F-binding pocket, whereas the RB-N757F (N) mutant is sufficient to inactivate the LxCxE-binding pocket. Each single mutant inhibits cell proliferation, but the RB-KN double mutant is defective in growth suppression. Nevertheless, the RB-KN mutant is capable of reducing etoposide-induced apoptosis. CONCLUSION/SIGNIFICANCE: Previous studies have established that RB-dependent G1-arrest can confer resistance to DNA damage-induced apoptosis. Results from this study demonstrate that RB can also inhibit apoptosis independent of growth suppression

Absorbing customer knowledge: how customer involvement enables service design success

Customers are a knowledge resource outside of the firm that can be utilized for new service success by involving them in the design process. However, existing research on the impact of customer involvement (CI) is inconclusive. Knowledge about customers’ needs and on how best to serve these needs (articulated in the service concept) is best obtained from customers themselves. However, codesign runs the risk of losing control of the service concept. This research argues that of the processes of external knowledge, acquisition (via CI), customer knowledge assimilation, and concept transformation form a capability that enables the firm to exploit customer knowledge in the form of a successful new service. Data from a survey of 126 new service projects show that the impact of CI on new service success is fully mediated by customer knowledge assimilation (the deep understanding of customers’ latent needs) and concept transformation (the modification of the service concept due to customer insights). However, its impact is more nuanced. CI exhibits an “∩”-shaped relationship with transformation, indicating there is a limit to the beneficial effect of CI. Its relationship with assimilation is “U” shaped, suggesting a problem with cognitive inertia where initial learnings are ignored. Customer knowledge assimilation directly impacts success, while concept transformation only helps success in the presence of resource slack. An evolving new service design is only beneficial if the firm has the flexibility to adapt to change

Development of a high-temperature diagnostics-while-drilling tool.

The envisioned benefits of Diagnostics-While-Drilling (DWD) are based on the principle that high-speed, real-time information from the downhole environment will promote better control of the drilling process. Although in practice a DWD system could provide information related to any aspect of exploration and production of subsurface resources, the current DWD system provides data on drilling dynamics. This particular set of new tools provided by DWD will allow quicker detection of problems, reduce drilling flat-time and facilitate more efficient drilling (drilling optimization) with the overarching result of decreased drilling costs. In addition to providing the driller with an improved, real-time picture of the drilling conditions downhole, data generated from DWD systems provides researchers with valuable, high fidelity data sets necessary for developing and validating enhanced understanding of the drilling process. Toward this end, the availability of DWD creates a synergy with other Sandia Geothermal programs, such as the hard-rock bit program, where the introduction of alternative rock-reduction technologies are contingent on the reduction or elimination of damaging dynamic effects. More detailed descriptions of the rationale for the program and early development efforts are described in more detail by others [SAND2003-2069 and SAND2000-0239]. A first-generation low-temperature (LT) DWD system was fielded in a series of proof-of-concept tests (POC) to validate functionality. Using the LT system, DWD was subsequently used to support a single-laboratory/multiple-partner CRADA (Cooperative Research and Development Agreement) entitled Advanced Drag Bits for Hard-Rock Drilling. The drag-bit CRADA was established between Sandia and four bit companies, and involved testing of a PDC bit from each company [Wise, et al., 2003, 2004] in the same lithologic interval at the Gas Technology Institute (GTI) test facility near Catoosa, OK. In addition, the LT DWD system has been fielded in cost-sharing efforts with an industrial partner to support the development of new generation hard-rock drag bits. Following the demonstrated success of the POC DWD system, efforts were initiated in FY05 to design, fabricate and test a high-temperature (HT) capable version of the DWD system. The design temperature for the HT DWD system was 225 C. Programmatic requirements dictated that a HT DWD tool be developed during FY05 and that a working system be demonstrated before the end of FY05. During initial design discussions regarding a high-temperature system it was decided that, to the extent possible, the HT DWD system would maintain functionality similar to the low temperature system, that is, the HT DWD system would also be designed to provide the driller with real-time information on bit and bottom-hole-assembly (BHA) dynamics while drilling. Additionally, because of time and fiscal constraints associated with the HT system development, the design of the HT DWD tool would follow that of the LT tool. The downhole electronics package would be contained in a concentrically located pressure barrel and the use of externally applied strain gages with thru-tool connectors would also be used in the new design. Also, in order to maximize the potential wells available for the HT DWD system and to allow better comparison with the low-temperature design, the diameter of the tool was maintained at 7-inches. This report discusses the efforts associated with the development of a DWD system capable of sustained operation at 225 C. This report documents work performed in the second phase of the Diagnostics-While-Drilling (DWD) project in which a high-temperature (HT) version of the phase 1 low-temperature (LT) proof-of-concept (POC) DWD tool was built and tested. Descriptions of the design, fabrication and field testing of the HT tool are provided. Background on prior phases of the project can be found in SAND2003-2069 and SAND2000-0239

Meeting Summary of The NYO3 5th NO-Age/AD Meeting and the 1st Norway-UK Joint Meeting on Aging and Dementia:Recent Progress on the Mechanisms and Interventional Strategies

Unhealthy aging poses a global challenge with profound healthcare and socioeconomic implications. Slowing down the aging process offers a promising approach to reduce the burden of a number of age-related diseases, such as dementia, and promoting healthy longevity in the old population. In response to the challenge of the aging population and with a view to the future, Norway and the United Kingdom are fostering collaborations, supported by a "Money Follows Cooperation agreement" between the 2 nations. The inaugural Norway-UK joint meeting on aging and dementia gathered leading experts on aging and dementia from the 2 nations to share their latest discoveries in related fields. Since aging is an international challenge, and to foster collaborations, we also invited leading scholars from 11 additional countries to join this event. This report provides a summary of the conference, highlighting recent progress on molecular aging mechanisms, genetic risk factors, DNA damage and repair, mitophagy, autophagy, as well as progress on a series of clinical trials (eg, using NAD+ precursors). The meeting facilitated dialogue among policymakers, administrative leaders, researchers, and clinical experts, aiming to promote international research collaborations and to translate findings into clinical applications and interventions to advance healthy aging.</p

Novel Oncogenic Transcription Factor Cooperation in RB-Deficient Cancer

The retinoblastoma tumor suppressor (RB) is a critical regulator of E2F-dependent transcription, controlling a multitude of protumorigenic networks including but not limited to cell-cycle control. Here, genome-wide assessment of E2F1 function after RB loss in isogenic models of prostate cancer revealed unexpected repositioning and cooperation with oncogenic transcription factors, including the major driver of disease progression, the androgen receptor (AR). Further investigation revealed that observed AR/E2F1 cooperation elicited novel transcriptional networks that promote cancer phenotypes, especially as related to evasion of cell death. These observations were reflected in assessment of human disease, indicating the clinical relevance of the AR/E2F1 cooperome in prostate cancer. Together, these studies reveal new mechanisms by which RB loss induces cancer progression and highlight the importance of understanding the targets of E2F1 function. SIGNIFICANCE: This study identifies that RB loss in prostate cancer drives cooperation between AR and E2F1 as coregulators of transcription, which is linked to the progression of advanced disease