Brief report: Search for DNA markers in two autistic males with the fragile X syndrome

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44601/1/10803_2005_Article_BF02211885.pd

Evaluating the End-User Experience of Private Browsing Mode

Nowadays, all major web browsers have a private browsing mode. However, the mode's benefits and limitations are not particularly understood. Through the use of survey studies, prior work has found that most users are either unaware of private browsing or do not use it. Further, those who do use private browsing generally have misconceptions about what protection it provides. However, prior work has not investigated \emph{why} users misunderstand the benefits and limitations of private browsing. In this work, we do so by designing and conducting a three-part study: (1) an analytical approach combining cognitive walkthrough and heuristic evaluation to inspect the user interface of private mode in different browsers; (2) a qualitative, interview-based study to explore users' mental models of private browsing and its security goals; (3) a participatory design study to investigate why existing browser disclosures, the in-browser explanations of private browsing mode, do not communicate the security goals of private browsing to users. Participants critiqued the browser disclosures of three web browsers: Brave, Firefox, and Google Chrome, and then designed new ones. We find that the user interface of private mode in different web browsers violates several well-established design guidelines and heuristics. Further, most participants had incorrect mental models of private browsing, influencing their understanding and usage of private mode. Additionally, we find that existing browser disclosures are not only vague, but also misleading. None of the three studied browser disclosures communicates or explains the primary security goal of private browsing. Drawing from the results of our user study, we extract a set of design recommendations that we encourage browser designers to validate, in order to design more effective and informative browser disclosures related to private mode

Production of Inactivated Influenza H5N1 Vaccines from MDCK Cells in Serum-Free Medium

BACKGROUND: Highly pathogenic influenza viruses pose a constant threat which could lead to a global pandemic. Vaccination remains the principal measure to reduce morbidity and mortality from such pandemics. The availability and surging demand for pandemic vaccines needs to be addressed in the preparedness plans. This study presents an improved high-yield manufacturing process for the inactivated influenza H5N1 vaccines using Madin-Darby canine kidney (MDCK) cells grown in a serum-free (SF) medium microcarrier cell culture system. PRINCIPAL FINDING: The current study has evaluated the performance of cell adaptation switched from serum-containing (SC) medium to several commercial SF media. The selected SF medium was further evaluated in various bioreactor culture systems for process scale-up evaluation. No significant difference was found in the cell growth in different sizes of bioreactors studied. In the 7.5 L bioreactor runs, the cell concentration reached to 2.3 × 10(6) cells/mL after 5 days. The maximum virus titers of 1024 Hemagglutinin (HA) units/50 µL and 7.1 ± 0.3 × 10(8) pfu/mL were obtained after 3 days infection. The concentration of HA antigen as determined by SRID was found to be 14.1 µg/mL which was higher than those obtained from the SC medium. A mouse immunogenicity study showed that the formalin-inactivated purified SF vaccine candidate formulated with alum adjuvant could induce protective level of virus neutralization titers similar to those obtained from the SC medium. In addition, the H5N1 viruses produced from either SC or SF media showed the same antigenic reactivity with the NIBRG14 standard antisera. CONCLUSIONS: The advantages of this SF cell-based manufacturing process could reduce the animal serum contamination, the cost and lot-to-lot variation of SC medium production. This study provides useful information to manufacturers that are planning to use SF medium for cell-based influenza vaccine production

Investigation of Griffithsin's Interactions with Human Cells Confirms Its Outstanding Safety and Efficacy Profile as a Microbicide Candidate

Many natural product-derived lectins such as the red algal lectin griffithsin (GRFT) have potent in vitro activity against viruses that display dense clusters of oligomannose N-linked glycans (NLG) on their surface envelope glycoproteins. However, since oligomannose NLG are also found on some host proteins it is possible that treatment with antiviral lectins may trigger undesirable side effects. For other antiviral lectins such as concanavalin A, banana lectin and cyanovirin-N (CV-N), interactions between the lectin and as yet undescribed cellular moieties have been reported to induce undesirable side effects including secretion of inflammatory cytokines and activation of host T-cells. We show that GRFT, unlike CV-N, binds the surface of human epithelial and peripheral blood mononuclear cells (PBMC) through an exclusively oligosaccharide-dependent interaction. In contrast to several other antiviral lectins however, GRFT treatment induces only minimal changes in secretion of inflammatory cytokines and chemokines by epithelial cells or human PBMC, has no measureable effect on cell viability and does not significantly upregulate markers of T-cell activation. In addition, GRFT appears to retain antiviral activity once bound to the surface of PBMC. Finally, RNA microarray studies show that, while CV-N and ConA regulate expression of a multitude of cellular genes, GRFT treatment effects only minimal alterations in the gene expression profile of a human ectocervical cell line. These studies indicate that GRFT has an outstanding safety profile with little evidence of induced toxicity, T-cell activation or deleterious immunological consequence, unique attributes for a natural product-derived lectin

Coordinated allele-specific histone acetylation at the differentially methylated regions of imprinted genes

Genomic imprinting is an epigenetic inheritance system characterized by parental allele-specific gene expression. Allele-specific DNA methylation and chromatin composition are two epigenetic modification systems that control imprinted gene expression. To get a general assessment of histone lysine acetylation at imprinted genes we measured allele-specific acetylation of a wide range of lysine residues, H3K4, H3K18, H3K27, H3K36, H3K79, H3K64, H4K5, H4K8, H4K12, H2AK5, H2BK12, H2BK16 and H2BK46 at 11 differentially methylated regions (DMRs) in reciprocal mouse crosses using multiplex chromatin immunoprecipitation SNuPE assays. Histone acetylation marks generally distinguished the methylation-free alleles from methylated alleles at DMRs in mouse embryo fibroblasts and embryos. Acetylated lysines that are typically found at transcription start sites exhibited stronger allelic bias than acetylated histone residues in general. Maternally methylated DMRs, that usually overlap with promoters exhibited higher levels of acetylation and a 10% stronger allele-specific bias than paternally methylated DMRs that reside in intergenic regions. Along the H19/Igf2 imprinted domain, allele-specific acetylation at each lysine residue depended on functional CTCF binding sites in the imprinting control region. Our results suggest that many different histone acetyltransferase and histone deacetylase enzymes must act in concert in setting up and maintaining reciprocal parental allelic histone acetylation at DMRs

Recording behaviour of indoor-housed farm animals automatically using machine vision technology: a systematic review

Large-scale phenotyping of animal behaviour traits is time consuming and has led to increased demand for technologies that can automate these procedures. Automated tracking of animals has been successful in controlled laboratory settings, but recording from animals in large groups in highly variable farm settings presents challenges. The aim of this review is to provide a systematic overview of the advances that have occurred in automated, high throughput image detection of farm animal behavioural traits with welfare and production implications. Peer-reviewed publications written in English were reviewed systematically following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. After identification, screening, and assessment for eligibility, 108 publications met these specifications and were included for qualitative synthesis. Data collected from the papers included camera specifications, housing conditions, group size, algorithm details, procedures, and results. Most studies utilized standard digital colour video cameras for data collection, with increasing use of 3D cameras in papers published after 2013. Papers including pigs (across production stages) were the most common (n = 63). The most common behaviours recorded included activity level, area occupancy, aggression, gait scores, resource use, and posture. Our review revealed many overlaps in methods applied to analysing behaviour, and most studies started from scratch instead of building upon previous work. Training and validation sample sizes were generally small (mean±s.d. groups = 3.8±5.8) and in data collection and testing took place in relatively controlled environments. To advance our ability to automatically phenotype behaviour, future research should build upon existing knowledge and validate technology under commercial settings and publications should explicitly describe recording conditions in detail to allow studies to be reproduced

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The Impact of Salient Privacy Information on Decision-Making

People value their privacy; however, they typically do not make the protection of their privacy a priority. Privacy is oftentimes not tangible, complicating the efforts of technology users to express and act according to their privacy needs. Additionally, people may not be fully aware of the risks they are subjecting themselves to once they use the Internet for financial transactions, or create profiles on online social networks. Companies post privacy policies inform people about their informational practices; but, this information is extremely difficult to use and typically not considered in users’ decision-making processes. Privacy concerns have also had an impact on users’ adoption of new technologies that share personal information. A plethora of mobile location-finding technologies applications have become available over the last two decades, but the products and services offered by the technology developers may not comprehensively address the privacy implications and privacy concerns surrounding their use. The design considerations for these products may not provide the necessarily amount of control or risk mitigation for users to ensure that their location information is not misused. In this thesis, I focus on the impact of salient privacy information on privacy concerns and behavior in two contexts: online shopping and the use of a mobile-location sharing technology. I examine several case studies focusing on the evolution of privacy attitudes after people use specific technologies. Based on the examination of the use of a location-sharing system, I highlight several design considerations for mobile-location application developers to ensure they address their users privacy concerns. I use the results of online surveys and user studies to provide concrete information on the impact of feedback on the comfort with using location-sharing technology. This research shows that users will pay a premium to purchase from websites that offer better privacy policies IF that privacy information is made visible and understandable. This research points to the importance of control in the management of privacy concerns. Whether it be mandated by legislation, or recommended in industry standards or design standards, offering users control in the form of understandable privacy policy information, or control over the disclosure of personal information by technology, is essential

Vicarious infringement creates a privacy ceiling

In high-tech businesses ranging from Internet service providers to e-commerce websites and music stores like Apple iTunes, there is considerable potential for collecting personal information about customers, monitoring their usage habits, or even exerting control over their behavior- for example, restricting what can be done with a purchased song. A privacy ceiling is an effective limit to these privacy intrusions, created by the perceived or actual legal liability of possessing too much information or control. As we show in this paper, the risk is not simply that of customer backlash, but liability for a customer’s actions, owing to the ability to identify, report, or prevent them from taking those actions. In some cases high-tech businesses have been obligated to divulge their store of personal information or to police their customers at the demand of third parties; this unwanted result derives from the possession of too much information or control for the company’s own good. We argue that vicarious infringement liability in particular creates a privacy ceiling, a point beyond which there is no economic incentive to intrude on a user’s privacy; and, indeed, there is an incentive to architect one’s business so that such intrusions are difficult or impossible