Exploring joint attention in American sign language: the influence of sign familiarity

5R01DC015272-07 - NIH/National Institute on Deafness & Communication Disordershttps://escholarship.org/uc/item/5kq2s523Published versio

Breaching Indigenous Law: Canadian Mining in Guatemala

This is a case study of a small Indigenous community in Guatemala that defied a powerful Canadian mining company by holding a community vote on whether to allow mining on its territory. The result of the vote – to stop mining activity on its territory – has not been honoured by the Canadian mining company. The dispute is being played out against a backdrop of intimidation and violence. The study reviews the major players in the dispute – the mining company, the Guatemalan government, the World Bank and the Canadian government – and concludes that they all have a stake in the profitability of the mine. There is a clear deficiency in the checks and balances needed to ensure that the Indigenous people are dealt with fairly. Drawing on ideas from the National Roundtables on Corporate Social Responsibility (“CSR”) and the Canadian Extractive Industry in Developing Countries (released in March 2007), the study suggests that at the present time, Canadian courts may be the only forum capable of holding the major actors accountable for their actions

Ansätze zur lokalen Bayes’schen Fusion von Informationsbeiträgen heterogener Quellen

Die Lösung diverser Aufgaben profitiert von der Informationsfusion oder setzt sie sogar voraus. Die Bayes’sche Fusionsmethodik ist anschaulich, fundiert und erfüllt die essentiellen Anforderungen an eine sinnvolle Methodik auch zur Fusion der Beiträge heterogener Informationsquellen. In vielen praktisch relevanten Aufgaben verursachen Bayes’sche Verfahren hohen, oft nicht tragbaren Aufwand. In der Arbeit werden neuartige Ansätze zur Bewältigung Bayes’scher Fusion formuliert und untersucht

Oil and gas companies invest in legislators that vote against the environment.

Do campaign contributions from oil and gas companies influence legislators to vote against the environment, or do these companies invest in legislators that have a proven antienvironmental voting record? Using 28 y of campaign contribution data, we find that evidence consistently supports the investment hypothesis: The more a given member of Congress votes against environmental policies, the more contributions they receive from oil and gas companies supporting their reelection

High frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells

CRISPR RNA-guided endonucleases (RGENs) have rapidly emerged as a facile and efficient platform for genome editing. Here, we use a human cell-based reporter assay to characterize off-target cleavage of Cas9-based RGENs. We find that single and double mismatches are tolerated to varying degrees depending on their position along the guide RNA (gRNA)-DNA interface. We readily detected off-target alterations induced by four out of six RGENs targeted to endogenous loci in human cells by examination of partially mismatched sites. The off-target sites we identified harbor up to five mismatches and many are mutagenized with frequencies comparable to (or higher than) those observed at the intended on-target site. Our work demonstrates that RGENs are highly active even with imperfectly matched RNA-DNA interfaces in human cells, a finding that might confound their use in research and therapeutic applications

A cost comparison of electronic and hybrid data collection systems in Ontario during pandemic and seasonal influenza vaccination campaigns

<p>Abstract</p> <p>Background</p> <p>During the pandemic (H1N1) 2009 influenza vaccination campaign, health regions in Canada collected client-level immunization data using fully electronic or hybrid systems, with the latter comprising both electronic and paper-based elements. The objective of our evaluation was to compare projected five-year costs associated with implementing these systems in Ontario public health units (PHUs) during pandemic and seasonal influenza vaccination campaigns.</p> <p>Methods</p> <p>Six PHUs provided equipment and staffing costs during the pandemic (H1N1) 2009 influenza vaccination campaign and staffing algorithms for seasonal campaigns. We standardized resources to population sizes 100,000, 500,000 and 1,000,000, assuming equipment lifetime of five years and public health vaccine administration rates of 18% and 2.5% for H1N1 and seasonal campaigns, respectively. Two scenarios were considered: Year 1 pandemic and Year 1 seasonal campaigns, each followed by four regular influenza seasons. Costs were discounted at 5%.</p> <p>Results</p> <p>Assuming a Year 1 pandemic, the five-year costs per capita for the electronic system decrease as PHU population size increases, becoming increasingly less costly than hybrid systems ($4.33 vs.$4.34 [100,000], $4.17 vs.$4.34 [500,000], $4.12 vs.$4.34 [1,000, 000]). The same trend is observed for the scenario reflecting five seasonal campaigns, with the electronic system being less expensive per capita than the hybrid system for all population sizes ($1.93 vs.$1.95 [100,000], $1.91 vs.$1.94 [500,000], $1.87 vs.$1.94 [1,000, 000]). Sensitivity analyses identified factors related to nurse hours as affecting the direction and magnitude of the results.</p> <p>Conclusions</p> <p>Five-year cost projections for electronic systems were comparable or less expensive than for hybrid systems, at all PHU population sizes. An intangible benefit of the electronic system is having data rapidly available for reporting.</p

Developing a Prototype Ground Station for the Processing, Exploitation, and Dissemination of pLEO Sensor Data

The Air Force’s Space and Missile Systems Center (SMC) recently executed a quick-turnaround (16 month) effort through the Defense Innovation Unit to develop a prototype ground architecture demonstrating low-latency processing, exploitation, and dissemination of data collected by notional multi-phenomenology sensors hosted on small satellites in a proliferated LEO constellation. This effort, led by the Southwest Research Institute and supported by teammates, Amazon Web Services, SpaceX, and SciTec, Inc., involved the modeling and simulation of a variety of different OPIR, EO/IR, and SAR data streams; transporting these data via space and ground networks; processing the data in the AWS cloud environment; and then disseminating resulting products to tactical users. In this paper, we present an overview of the data transport and mission data processing, performance results from the application of our various Mission Data Processing Chains, a summary of our findings on the latencies associated with both data transport and data processing, and lessons learned including insight into ground-based vs. on-board processing

Disulfiram use is associated with lower risk of COVID-19: A retrospective cohort study.

Funder: British Heart FoundationFunder: VA Boston Healthcare SystemFunder: Dana-Farber Cancer InstituteFunder: VA Cooperative Studies ProgramFunder: National Institutes of HealthFunder: Harvard Medical SchoolEffective, low-cost therapeutics are needed to prevent and treat COVID-19. Severe COVID-19 disease is linked to excessive inflammation. Disulfiram is an approved oral drug used to treat alcohol use disorder that is a potent anti-inflammatory agent and an inhibitor of the viral proteases. We investigated the potential effects of disulfiram on SARS-CoV-2 infection and disease severity in an observational study using a large database of clinical records from the national US Veterans Affairs healthcare system. A multivariable Cox regression adjusted for demographic information and diagnosis of alcohol use disorder revealed a reduced risk of SARS-CoV-2 infection with disulfiram use at a hazard ratio of 0.66 (34% lower risk, 95% confidence interval 24-43%). There were no COVID-19 related deaths among the 188 SARS-CoV-2 positive patients treated with disulfiram, in contrast to 5-6 statistically expected deaths based on the untreated population (P = 0.03). Our epidemiological results suggest that disulfiram may contribute to the reduced incidence and severity of COVID-19. These results support carefully planned clinical trials to assess the potential therapeutic effects of disulfiram in COVID-19

Non-thermal plasma modulates cellular markers associated with immunogenicity in a model of latent HIV-1 infection

Effective control of infection by human immunodeficiency virus type 1 (HIV-1), the causative agent of the acquired immunodeficiency syndrome (AIDS), requires continuous and life-long use of anti-retroviral therapy (ART) by people living with HIV-1 (PLWH). In the absence of ART, HIV-1 reemergence from latently infected cells is ineffectively suppressed due to suboptimal innate and cytotoxic T lymphocyte responses. However, ART-free control of HIV-1 infection may be possible if the inherent immunological deficiencies can be reversed or restored. Herein we present a novel approach for modulating the immune response to HIV-1 that involves the use of non-thermal plasma (NTP), which is an ionized gas containing various reactive oxygen and nitrogen species (RONS). J-Lat cells were used as a model of latent HIV-1 infection to assess the effects of NTP application on viral latency and the expression of pro-phagocytic and pro-chemotactic damage-associated molecular patterns (DAMPs). Exposure of J-Lat cells to NTP resulted in stimulation of HIV-1 gene expression, indicating a role in latency reversal, a necessary first step in inducing adaptive immune responses to viral antigens. This was accompanied by the release of pro-inflammatory cytokines and chemokines including interleukin-1β (IL-1β) and interferon-γ (IFN-γ); the display of pro-phagocytic markers calreticulin (CRT), heat shock proteins (HSP) 70 and 90; and a correlated increase in macrophage phagocytosis of NTP-exposed J-Lat cells. In addition, modulation of surface molecules that promote or inhibit antigen presentation was also observed, along with an altered array of displayed peptides on MHC I, further suggesting methods by which NTP may modify recognition and targeting of cells in latent HIV-1 infection. These studies represent early progress toward an effective NTP-based ex vivo immunotherapy to resolve the dysfunctions of the immune system that enable HIV-1 persistence in PLWH

In silico abstraction of zinc finger nuclease cleavage profiles reveals an expanded landscape of off-target sites

Gene-editing nucleases enable targeted modification of DNA sequences in living cells, thereby facilitating efficient knockout and precise editing of endogenous loci. Engineered nucleases also have the potential to introduce mutations at off-target sites of action. Such unintended alterations can confound interpretation of experiments and can have implications for development of therapeutic applications. Recently, two improved methods for identifying the off-target effects of zinc finger nucleases (ZFNs) were described–one using an in vitro cleavage site selection method and the other exploiting the insertion of integration-defective lentiviruses into nuclease-induced double-stranded DNA breaks. However, application of these two methods to a ZFN pair targeted to the human CCR5 gene led to identification of largely non-overlapping off-target sites, raising the possibility that additional off-target sites might exist. Here, we show that in silico abstraction of ZFN cleavage profiles obtained from in vitro cleavage site selections can greatly enhance the ability to identify potential off-target sites in human cells. Our improved method should enable more comprehensive profiling of ZFN specificities