1,256 research outputs found
Researcher Access to Born-Digital Collections: an Exploratory Study
While a small, but growing number of institutions offer access to born-digital collections, there is scant literature documenting researcher interaction with these materials. This paper addresses this gap through documenting and analyzing researcher interactions to portions of born-digital collections at New York University (NYU) Libraries, with the cooperation of NYU’s Fales Library and Special Collection and the Digital Library and Technology Solutions Department, as well as the National Digital Stewardship Residency (NDSR) program. From September 2014-May 2015, NYU Libraries began implementing an “access-driven” born-digital workflow for their 3 archives: Fales Library and Special Collections, NYU University Archives, and the Tamiment Library and Robert F. Wagner Archives, using several model collections as part of a 9 month NDSR project. One goal was to provide access to these collections by the end of the project period. The project concluded with 5 researcher interviews investigating how researchers navigate, understand, and value forms of born-digital access. This paper will focus on these interviews and how new forms of access were interpreted and received
What’s Wrong with Digital Stewardship: Evaluating the Organization of Digital Preservation Programs from Practitioners’ Perspectives
The National Digital Stewardship Alliance surveyed practitioners in 2012 and again in 2017 to gauge, among other things, how satisfied they were with their organizations’ digital preservation function. This study seeks to understand what causes the high and rising levels of dissatisfaction that practitioners reported. We interviewed 21 digital stewards and asked them to describe the organizational context in which they work; to reflect on what aspects of their organizations’ approach to digital preservation are working well and which are not; and to evaluate necessary areas of improvement. We identified experiences that were common among participants using a qualitative research methodology based on phenomenology. These conversations revealed that practitioners largely consider digital stewardship values and goals to be misunderstood at an organizational level, and demonstrated that the absence of a long-term vision for digital stewardship disempowers practitioners
CD7-deleted hematopoietic stem cells can restore immunity after CAR T cell therapy
Targeting T cell malignancies with universal CD7-targeting chimeric antigen receptor T cells (UCART7) can lead to profound immune deficiency due to loss of normal T and NK cells. While a small population of endogenous CD7- T cells exists, these cells are unlikely to be able to repopulate the entire immune repertoire after UCART7 treatment, as they are limited in number and proliferative capacity. To rescue T and NK cells after UCART7, we created hematopoietic stem cells genetically deleted for CD7 (CD7-KO HSCs). CD7-KO HSCs were able to engraft immunodeficient mice and differentiate into T and NK cells lacking CD7 expression. CD7-KO T and NK cells could perform effector functions as robustly as control T and NK cells. Furthermore, CD7-KO T cells were phenotypically and functionally distinct from endogenous CD7- T cells, indicating that CD7-KO T cells can supplement immune functions lacking in CD7- T cells. Mice engrafted with CD7-KO HSCs maintained T and NK cell numbers after UCART7 treatment, while these were significantly decreased in control mice. These studies support the development of CD7-KO HSCs to augment host immunity in patients with T cell malignancies after UCART7 treatment
Structure and physical properties of the noncentrosymmetric superconductor Mo3 Al2 C
We have synthesized polycrystalline samples of the noncentrosymmetric superconductor Mo3 Al2 C by arc and RF melting, measured its transport, magnetic and thermodynamic properties, and computed its band structure. Experimental results indicate a bulk superconducting transition at Tc ∼9.2 K while the density of states at the Fermi surface is found to be dominated by Mod orbitals. Using the measured values for the lower critical field Hc1, upper critical field Hc2, and the specific heat C, we estimated the thermodynamic critical field Hc(0), coherence length ξ (0), penetration depth λ (0), and the Ginzburg-Landau parameter κ (0). The specific-heat jump at Tc, ΔC/γ Tc =2.14, suggests that Mo3 Al 2 C is moderately to strongly coupled, consistent with the fast opening of the gap, as evidenced by the rapid release of entropy below Tc from our electronic specific-heat measurements. Above 2 K the electronic specific heat exhibits the power-law behavior, suggesting that synthesis of single crystals and measurements at lower temperature are needed to establish whether the gap is anisotropic. The estimated value of the upper critical field H c2 (0) is close to the calculated Pauli limit, therefore further studies are needed to determine whether the absence of an inversion center results in a significant admixture of the triplet component of the order parameter. © 2010 The American Physical Society
Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer.
Although targeted therapies often elicit profound initial patient responses, these effects are transient due to residual disease leading to acquired resistance. How tumors transition between drug responsiveness, tolerance and resistance, especially in the absence of preexisting subclones, remains unclear. In epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cells, we demonstrate that residual disease and acquired resistance in response to EGFR inhibitors requires Aurora kinase A (AURKA) activity. Nongenetic resistance through the activation of AURKA by its coactivator TPX2 emerges in response to chronic EGFR inhibition where it mitigates drug-induced apoptosis. Aurora kinase inhibitors suppress this adaptive survival program, increasing the magnitude and duration of EGFR inhibitor response in preclinical models. Treatment-induced activation of AURKA is associated with resistance to EGFR inhibitors in vitro, in vivo and in most individuals with EGFR-mutant lung adenocarcinoma. These findings delineate a molecular path whereby drug resistance emerges from drug-tolerant cells and unveils a synthetic lethal strategy for enhancing responses to EGFR inhibitors by suppressing AURKA-driven residual disease and acquired resistance
Beyond the periodic orbit theory
The global constraints on chaotic dynamics induced by the analyticity of
smooth flows are used to dispense with individual periodic orbits and derive
infinite families of exact sum rules for several simple dynamical systems. The
associated Fredholm determinants are of particularly simple polynomial form.
The theory developed suggests an alternative to the conventional periodic orbit
theory approach to determining eigenspectra of transfer operators.Comment: 29 pages Latex2
Therapeutic DNA vaccine induces broad T cell responses in the gut and sustained protection from viral rebound and AIDS in SIV-infected rhesus macaques.
Immunotherapies that induce durable immune control of chronic HIV infection may eliminate the need for life-long dependence on drugs. We investigated a DNA vaccine formulated with a novel genetic adjuvant that stimulates immune responses in the blood and gut for the ability to improve therapy in rhesus macaques chronically infected with SIV. Using the SIV-macaque model for AIDS, we show that epidermal co-delivery of plasmids expressing SIV Gag, RT, Nef and Env, and the mucosal adjuvant, heat-labile E. coli enterotoxin (LT), during antiretroviral therapy (ART) induced a substantial 2-4-log fold reduction in mean virus burden in both the gut and blood when compared to unvaccinated controls and provided durable protection from viral rebound and disease progression after the drug was discontinued. This effect was associated with significant increases in IFN-γ T cell responses in both the blood and gut and SIV-specific CD8+ T cells with dual TNF-α and cytolytic effector functions in the blood. Importantly, a broader specificity in the T cell response seen in the gut, but not the blood, significantly correlated with a reduction in virus production in mucosal tissues and a lower virus burden in plasma. We conclude that immunizing with vaccines that induce immune responses in mucosal gut tissue could reduce residual viral reservoirs during drug therapy and improve long-term treatment of HIV infection in humans
Reliability generalization for the Motivated Strategies for Learning Questionnaire: A meta-analytic view of reliability estimates
A reliability generalization meta-analysis was performed to explore the relationship between study factors and levels of alpha reliability for the 15 subscales of the Motivated Strategies for Learning Questionnaire (MSLQ). The MSLQ has been widely adapted over the past 25 years to investigate the role of motivation and strategies in learning, primarily at the postsecondary level. A literature search from the years 1991 to 2015 yielded 295 peer-reviewed journal articles and 1,369 alpha reliability coefficients. Articles were coded for six potential moderator study variables. A novel varying coefficient (VC) model was adopted to determine average reliabilities across studies for each subscale and to perform multiple regression analyses to identify study variables that may moderate alpha reliability estimates. Commonality analyses were used to aid in interpretation of regression results. Meta-analyzed alpha reliabilities were lower than values published in the test manual for all but three of the subscales. Ability of specific moderators to predict score reliability varied across subscales; however, studies in North America, in English, or using a 7-point response scale generally corresponded to increased reliability estimates. Knowledge of expected levels of score reliability under varying sample and study conditions may provide useful information for researchers planning future use of the MSLQ
Defining a Minimum Set of Standardized Patient-centered Outcome Measures for Macular Degeneration
Purpose To define a minimum set of outcome measures for tracking, comparing, and improving macular degeneration care. Design Recommendations from a working group of international experts in macular degeneration outcomes registry development and patient advocates, facilitated by the International Consortium for Health Outcomes Measurement (ICHOM). Methods Modified Delphi technique, supported by structured teleconferences, followed by online surveys to drive consensus decisions. Potential outcomes were identified through literature review of outcomes collected in existing registries and reported in major clinical trials. Outcomes were refined by the working group and selected based on impact on patients, relationship to good clinical care, and feasibility of measurement in routine clinical practice. Results Standardized measurement of the following outcomes is recommended: visual functioning and quality of life (distance visual acuity, mobility and independence, emotional well-being, reading and accessing information); number of treatments; complications of treatment; and disease control. Proposed data collection sources include administrative data, clinical data during routine clinical visits, and patient-reported sources annually. Recording the following clinical characteristics is recommended to enable risk adjustment: age; sex; ethnicity; smoking status; baseline visual acuity in both eyes; type of macular degeneration; presence of geographic atrophy, subretinal fibrosis, or pigment epithelial detachment; previous macular degeneration treatment; ocular comorbidities. Conclusions The recommended minimum outcomes and pragmatic reporting standards should enable standardized, meaningful assessments and comparisons of macular degeneration treatment outcomes. Adoption could accelerate global improvements in standardized data gathering and reporting of patient-centered outcomes. This can facilitate informed decisions by patients and health care providers, plus allow long-term monitoring of aggregate data, ultimately improving understanding of disease progression and treatment responses
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