Internet as a Human Right: A Practical Legal Framework to Address the Unique Nature of the Medium and to Promote Development

A Taiwanese court sentenced a blogger to 30 days of detention for her comments that a restaurant’s food was too salty and that the locale was unsanitary. In Indonesia, a woman was sentenced to six months in jail for libel after an e-mail she sent to friends about poor treatment she received in a hospital was posted on Facebook. These are not isolated cases of persecution, but part of a broad pattern of challenges facing individuals around the world. The United Nations recently released a report on legal trends involving restriction of expression on the Internet, declaring that freedom of expression on the Internet is a human right. If Internet freedom is a human right, what are the limits of that entitlement? This Essay explores existing legal models and restrictions on online communication through case studies, including discussion of restrictions in countries affected by the Arab Spring of 2011. This Essay suggests six basic elements for a legal framework that can support the unique challenges presented by the Internet as it becomes a primary mode of communication

Carbonic anhydrase III (Car3) is not required for fatty acid synthesis and does not protect against high-fat diet induced obesity in mice

Carbonic anhydrases are a family of enzymes that catalyze the reversible condensation of water and carbon dioxide to carbonic acid, which spontaneously dissociates to bicarbonate. Carbonic anhydrase III (Car3) is nutritionally regulated at both the mRNA and protein level. It is highly enriched in tissues that synthesize and/or store fat: liver, white adipose tissue, brown adipose tissue, and skeletal muscle. Previous characterization of Car3 knockout mice focused on mice fed standard diets, not high-fat diets that significantly alter the tissues that highly express Car3. We observed lower protein levels of Car3 in high-fat diet fed mice treated with niclosamide, a drug published to improve fatty liver symptoms in mice. However, it is unknown if Car3 is simply a biomarker reflecting lipid accumulation or whether it has a functional role in regulating lipid metabolism. We focused our in vitro studies toward metabolic pathways that require bicarbonate. To further determine the role of Car3 in metabolism, we measured de novo fatty acid synthesis with in vitro radiolabeled experiments and examined metabolic biomarkers in Car3 knockout and wild type mice fed high-fat diet. Specifically, we analyzed body weight, body composition, metabolic rate, insulin resistance, serum and tissue triglycerides. Our results indicate that Car3 is not required for de novo lipogenesis, and Car3 knockout mice fed high-fat diet do not have significant differences in responses to various diets to wild type mice

ManyDogs Project: A Big Team Science Approach to Investigating Canine Behavior and Cognition

Dogs have a special place in human history as the first domesticated species and play important roles in many cultures around the world. However, their role in scientific studies has been relatively recent. With a few notable exceptions (e.g., Darwin, Pavlov, Scott, and Fuller), domestic dogs were not commonly the subject of rigorous scientific investigation of behavior until the late 1990s. Although the number of canine science studies has increased dramatically over the last 20 years, most research groups are limited in the inferences they can draw because of the relatively small sample sizes used, along with the exceptional diversity observed in dogs (e.g., breed, geographic location, experience). To this end, we introduce the ManyDogs Project, an international consortium of researchers interested in taking a big team science approach to understanding canine behavioral science. We begin by discussing why studying dogs provides valuable insights into behavior and cognition, evolutionary processes, human health, and applications for animal welfare. We then highlight other big team science projects that have previously been conducted in canine science and emphasize the benefits of our approach. Finally, we introduce the ManyDogs Project and our mission: (a) replicating important findings, (b) investigating moderators that need a large sample size such as breed differences, (c) reaching methodological consensus, (d) investigating cross-cultural differences, and (e) setting a standard for replication studies in general. In doing so, we hope to address previous limitations in individual lab studies and previous big team science frameworks to deepen our understanding of canine behavior and cognition

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

Being user-oriented: convergences, divergences, and the potentials for systematic dialogue between disciplines and between researchers, designers, and providers

The challenge this panel addresses is drawn from intersecting literature reviews and critical commentaries focusing on: 1) user studies in multiple fields; and 2) the difficulties of bringing different disciplines and perspectives to bear on user‐oriented research, design, and practice. 1 The challenge is that while we have made some progress in collaborative work, we have some distance to go to become user‐oriented in inter‐disciplinary and inter‐perspective ways. The varieties of our approaches and solutions are, as some observers suggest, an increasing cacophony. One major difficulty is that most discussions are solution‐oriented, offering arguments of this sort ‐‐ if only we addressed users in this way… Each solution becomes yet another addition to the cacophony. This panel implements a central approach documented for its utility by communication researchers and long used by communication mediators and negotiators ‐‐ that of focusing not on communication but rather on meta‐communication: communicating about communication. The intent in the context of this panel is to help us refocus attention from too frequent polarizations between alternative solutions to the possibility of coming to understand what is behind the alternatives and where they point to experientially‐based convergences and divergences, both of which might potentially contribute to synergies. The background project for this panel comes from a series of in‐depth interviews with expert researchers, designers, and providers in three field groupings ‐‐ library and information science; human computer interaction/information technology; and communication and media studies. One set of interviews involved 5‐hour focus groups with directors of academic and public libraries serving 44 colleges and universities in central Ohio; the second involved one‐on‐one interviews averaging 50 minutes with 81 nationally‐internationally known experts in the 3 fields, 25‐27 interviews per field. Using Dervin\u27s Sense‐Making Methodological approach to interviewing, the expert interviews of both kinds asked each interviewee: what he/she considered to be the big unanswered questions about users and what explained why the questions have not been answered; and, what he/she saw as hindering versus helping in attempts to communicate about users across disciplinary and perspective gaps. 2 The panel consists of six teams, two from each field. Prior to the panel presentation at ASIST, each team will have read the set of interviews and completed impressionistic essays of what patterns and themes they saw as emerging. At this stage, team members will purposively not homogenize their differences and most will write solo‐authored essays that will be placed on a web‐site accessible to ASIST members prior to the November meeting. In addition, at least one systematic analysis will be completed and available online. 3 At the ASIST panel, each team\u27s leader will present a brief and intentionally provocative impressionist account of what his/her team came to understand about our struggles communicating across fields and perspectives about users. Again, each team will purposively not homogenize its own differences in viewpoints, but rather highlight them as fodder for discussion. A major purpose will be to invite audience members to join the panel in discussion. At least 20 minutes will be left open for this purpose

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

A community-based physical activity intervention to prevent mobility-related disability for retired older people (REtirement in ACTion (REACT)): Study protocol for a randomised controlled trial

© 2018 The Author(s). Background: The REtirement in ACTion (REACT) study is a multi-centre, pragmatic, two-arm, parallel-group randomised controlled trial (RCT) with an internal pilot phase. It aims to test the effectiveness and cost-effectiveness of a community, group-based physical activity intervention for reducing, or reversing, the progression of functional limitations in older people who are at high risk of mobility-related disability. Methods/design: A sample of 768 sedentary, community-dwelling, older people aged 65 years and over with functional limitations, but who are still ambulatory (scores between 4 and 9 out of 12 in the Short Physical Performance Battery test (SPPB)) will be randomised to receive either the REACT intervention, delivered over a period of 12 months by trained facilitators, or a minimal control intervention. The REACT study incorporates comprehensive process and economic evaluation and a nested sub-study which will test the hypothesis that the REACT intervention will slow the rate of brain atrophy and of decline in cognitive function assessed using magnetic resonance imaging (MRI). Outcome data will be collected at baseline, 6, 12 and 24 months for the main study, with MRI sub-study data collected at baseline, 6 and 12 months. The primary outcome analysis (SPPB score at 24 months) will be undertaken blinded to group allocation. Primary comparative analyses will be on an intention-to-treat (ITT) basis with due emphasis placed on confidence intervals. Discussion: REACT represents the first large-scale, pragmatic, community-based trial in the UK to target the non-disabled but high-risk segment of the older population with an intervention to reduce mobility-related disability. A programme that can successfully engage this population in sufficient activity to improve strength, aerobic capacity, coordination and balance would have a major impact on sustaining health and independence. REACT is also the first study of its kind to conduct a full economic and comprehensive process evaluation alongside the RCT. If effective and cost-effective, the REACT intervention has strong potential to be implemented widely in the UK and elsewhere

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts