A New Synthesis: Research Resources to Research Experiences

Libraries should develop a new model for providing information resources and analytical tools for the use of scholars working in the current multidisciplinary research environment. This model, A New Synthesis, based on today’s research experience should replace the present concept of the “collection budget.” Sources are proliferating and traditional scholarly resources are no longer at the core. Research itself has changed. Previously, finding information was primary, but now information is plentiful and today’s challenges are to understand, analyze, and extract insight from these vast resources. To address this challenge, newly designed libraries are appearing that are radically different, reconceptualizing learning spaces, technological infrastructure, and research labs for scholars and students. Yet, the concept of the collection budget is little changed. We must embrace a paradigm that allows us to envision holistically the development and investment necessary to support current research. To enable expanded capacity for supporting today’s Grand Challenge research and to ensure the critical relevancy of academic libraries in this endeavor, we must employ a new synthesis. Sources can no longer be viewed independently from the tools needed to analyze them. Critical elements include: redeploying funds to an array of open platforms; shifting the focus from access to knowledge creation; and investing in spaces, technology, and people that will help researchers solve problems in new ways. We are at a moment when building these services and placing them at the heart of libraries requires fundamental organizational and financial change. Reconceiving current spending on collections is essential to this change

Minimal, superficial DNA damage in human skin from filtered far-ultraviolet C

Funding: This study was funded in part by MR/P012248/1 to R.P.H. from the Medical Research Council.Publisher PDFPeer reviewe

Tilting the balance between RNA interference and replication eradicates Leishmania RNA virus 1 and mitigates the inflammatory response.

Many Leishmania (Viannia) parasites harbor the double-stranded RNA virus Leishmania RNA virus 1 (LRV1), which has been associated with increased disease severity in animal models and humans and with drug treatment failures in humans. Remarkably, LRV1 survives in the presence of an active RNAi pathway, which in many organisms controls RNA viruses. We found significant levels (0.4 to 2.5%) of small RNAs derived from LRV1 in both Leishmania braziliensis and Leishmania guyanensis, mapping across both strands and with properties consistent with Dicer-mediated cleavage of the dsRNA genome. LRV1 lacks cis- or trans-acting RNAi inhibitory activities, suggesting that virus retention must be maintained by a balance between RNAi activity and LRV1 replication. To tilt this balance toward elimination, we targeted LRV1 using long-hairpin/stem-loop constructs similar to those effective against chromosomal genes. LRV1 was completely eliminated, at high efficiency, accompanied by a massive overproduction of LRV1-specific siRNAs, representing as much as 87% of the total. For both L. braziliensis and L. guyanensis, RNAi-derived LRV1-negative lines were no longer able to induce a Toll-like receptor 3-dependent hyperinflammatory cytokine response in infected macrophages. We demonstrate in vitro a role for LRV1 in virulence of L. braziliensis, the Leishmania species responsible for the vast majority of mucocutaneous leishmaniasis cases. These findings establish a targeted method for elimination of LRV1, and potentially of other Leishmania viruses, which will facilitate mechanistic dissection of the role of LRV1-mediated virulence. Moreover, our data establish a third paradigm for RNAi-viral relationships in evolution: one of balance rather than elimination

Localization of IFN-γ-Activated Stat1 and IFN Regulatory Factors 1 and 2 in Breast Cancer Cells

The aim of the present work was to evaluate the induction and localization of Stat1, interferon (IFN) regulatory factor-1 (IRF-1), and IRF-2 after IFN-γ exposure of human breast cancer cell lines, SKBR3, MDA468, MCF7, and BT20. Results from growth assays, Western staining, electrophoretic mobility shift assay (EMSA), and immunohistochemical staining were collated to test our hypothesis that immunohistochemical analysis of Stat1, IRF-1, and IRF-2 would provide additional information about the functionality of the IFN-γ signaling pathway in human tumor lines. EMSA results showed that in each of four cell lines, Stat1 expression was increased and demonstrated functional activity after IFN-γ stimulation. Western and EMSA analysis showed upregulation of IRF-1 but not IRF-2 in each cell line. Confocal microscopy of cells stained for Stat1, IRF-1, and IRF-2 confirmed the results and also provided novel information about the intracellular localization of proteins and intercellular variations in responses. The proportion of cells with IRF-1 stimulation and translocation was positively correlated with the IFN-γ growth suppression in vitro. In conclusion, using four independent assays, we have demonstrated that heterogeneity in IFN-γ-mediated upregulation of signal transduction proteins can be detected in vitro and that these differences can explain distinct cellular growth effects.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63148/1/107999003322558755.pd

A Comparative Study of the ReCell® Device and Autologous Spit-Thickness Meshed Skin Graft in the Treatment of Acute Burn Injuries.

Early excision and autografting are standard care for deeper burns. However, donor sites are a source of significant morbidity. To address this, the ReCell® Autologous Cell Harvesting Device (ReCell) was designed for use at the point-of-care to prepare a noncultured, autologous skin cell suspension (ASCS) capable of epidermal regeneration using minimal donor skin. A prospective study was conducted to evaluate the clinical performance of ReCell vs meshed split-thickness skin grafts (STSG, Control) for the treatment of deep partial-thickness burns. Effectiveness measures were assessed to 1 year for both ASCS and Control treatment sites and donor sites, including the incidence of healing, scarring, and pain. At 4 weeks, 98% of the ASCS-treated sites were healed compared with 100% of the Controls. Pain and assessments of scarring at the treatment sites were reported to be similar between groups. Significant differences were observed between ReCell and Control donor sites. The mean ReCell donor area was approximately 40 times smaller than that of the Control (P < .0001), and after 1 week, significantly more ReCell donor sites were healed than Controls (P = .04). Over the first 16 weeks, patients reported significantly less pain at the ReCell donor sites compared with Controls (P ≤ .05 at each time point). Long-term patients reported higher satisfaction with ReCell donor site outcomes compared with the Controls. This study provides evidence that the treatment of deep partial-thickness burns with ASCS results in comparable healing, with significantly reduced donor site size and pain and improved appearance relative to STSG

Search for the Neutron Decay n→\rightarrow X+γ\gamma where X is a dark matter particle

In a recent paper submitted to Physical Review Letters, Fornal and Grinstein have suggested that the discrepancy between two different methods of neutron lifetime measurements, the beam and bottle methods can be explained by a previously unobserved dark matter decay mode, n$\rightarrow$ X+$\gamma$ where X is a dark matter particle. We have performed a search for this decay mode over the allowed range of energies of the monoenergetic gamma ray for X to be a dark matter particle. We exclude the possibility of a sufficiently strong branch to explain the lifetime discrepancy with greater than 4 sigma confidence.Comment: 6 pages 3 figure

Determination of the Axial-Vector Weak Coupling Constant with Ultracold Neutrons

A precise measurement of the neutron decay $\beta$-asymmetry $A_0$ has been carried out using polarized ultracold neutrons (UCN) from the pulsed spallation UCN source at the Los Alamos Neutron Science Center (LANSCE). Combining data obtained in 2008 and 2009, we report $A_0 = -0.11966 \pm 0.00089_{-0.00140}^{+0.00123}$, from which we determine the ratio of the axial-vector to vector weak coupling of the nucleon $g_A/g_V = -1.27590_{-0.00445}^{+0.00409}$.Comment: 5 pages, 2 figure