iVici: Interrelational Visualization and Correlation Interface

Affiliation: Département de Biochimie, Faculté de médecine, Université de MontréalWe have developed an application, iVici, to analyze cellular networks represented as addressable symmetric or asymmetric two-dimensional matrices. iVici was designed to permit simultaneous visualization and correlation of multiple datasets, representing any relationship between a set of genes, mRNAs, or proteins. Visual overlay of datasets and addressable access to gene annotations permits comparison of networks of different types (for example protein-protein interactions and genetic networks) or investigation of the dynamic reorganization of a particular network

The case for sobriety checkpoints in Texas

Examines data that suggests that sobriety checkpoints have significantly reduced injuries and deaths due to impaired drivers

Information Security Framework for Small and Medium Sized Businesses

2006-05-19 (Removed from collection 2006-11-21) Revised version reinstated 2009-06-17Information security issues are a challenge to everyone who uses computers. The rise of the personal computer as a common business tool and the Internet as a common means of business communication and commerce have also created an environment that criminals with technical knowledge can exploit to prey upon the less technically savvy. The cost of computer crime to business in the United States has risen to $67 billion according to the 2005 FBI Computer Crime Survey. Not a day goes by that a computer security exploit or identity theft scheme makes national headlines. The impact to small and medium sized businesses is tremendous. These businesses have the least amount of resources to use to help defend against hacker attacks and they suffer some of the largest net financial impacts when victimized by an attack. The good news is that there are some simple things a business owner can do to greatly reduce the risks of being victimized by an information security failure. Education and awareness of the most prevalent risks to business information and commonly exploited security holes can quickly close the door to a security incident. Just as with traditional burglary attempts, the computer criminals will first look for the path of least resistance when trying to break in to a computer system. If a door is unlocked, all the criminal has to do is walk right in. The problem with computer technology is that many people do not even know when the doors are unlocked. By raising awareness of the most common vectors of attacks against business computer systems, this field project seeks to help business owners better manage and protect their information assets. The computer risks and mitigation approaches outlined in this project will not completely eliminate all the computer security exposures that company can face in the 21st century business environment but they will help a business owner know what they can do to quickly reduce their risk exposure. Just like with any other type of crime, a determined criminal may eventually find some type of security weakness that can be exploited for illicit purposes. The goal of the business owner is to make the criminal’s work so hard that they look elsewhere to commit their crimes

Phase diagram determination and relative dielectric constant measurements of the butyronitrile-chloroethane system

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 1995.Includes bibliographical references (p. 164-168).by Robin Beth Michnick.Ph.D

Beyond Counting Words: A paradigm Shift for the Study of Language Acquisition

The 30-million-word gap, the quantified difference in the amount of speech that children growing up in low-resourced homes hear compared to their peers from high-resourced homes, is a phrase that has entered the collective consciousness. In the discussion of quantity, the complex and nuanced environments in which children learn language were distilled into a singular metric—number of words. In this article, we propose examining children’s language environments by focusing on what caregivers communicate to children and how they communicate it. Focusing on the features of the language environment promotes a more inclusive approach to understanding how children learn and the diverse contexts in which that learning occurs

Assessing the Language of 2-year-olds: From Theory to Practice

Early screening for language problems is a priority given the importance of language for success in school and interpersonal relationships. The paucity of reliable behavioral instruments for this age group prompted the development of a new touchscreen language screener for 2-year-olds that relies on language comprehension. Developmental literature guided selection of age-appropriate markers of language disorder risk that are culturally and dialectally neutral and could be reliably assessed. Items extend beyond products of linguistic knowledge (vocabulary and syntax) and tap the process by which children learn language, also known as fast mapping. After piloting an extensive set of items (139), two phases of testing with over 500 children aged 2; 0–2; 11 were conducted to choose the final 40-item set. Rasch analysis was used to select the best fitting and least redundant items. Norms were created based on 270 children. Sufficient test-retest reliability, Cronbach\u27s alpha, and convergent validity with the MB-CDI and PPVT are reported. This quick behavioral measure of language capabilities could support research studies and facilitate the early detection of language problems

Portrait of early science education in majority dual language learner classrooms: Where do we start?

Despite the growing interest in early science education, there is much left to be explored, particularly in majority Dual Language Learning (DLL) classrooms. The current study examined 1) early science opportunities across classroom contexts in majority Spanish-English DLL Head Start classrooms, 2) the languages (i.e., English and Spanish) that teachers used to engage DLL children in science, 3) and how teachers’ discussion of scientific and engineering practices and disciplinary core ideas related to children’s academic outcomes. In a sample of 411 children (ages 3-5) from 34 Head Start classrooms, the current study found that teachers discussed and encouraged more practices during science lessons than circle time, dramatic play, and story time. There were no differences in teachers’ discussion of core ideas across contexts. Teachers used the same amount of English and Spanish to discuss practices and core ideas. Teaching physical science was associated with children’s science outcomes. Making observations and discussing life science were associated with children’s math outcomes. Teaching math, making observations, and developing and using models were related to children’s executive functioning. Findings from this study demonstrate that science opportunities occur across preschool classroom settings. Additionally, it provides evidence that teachers may be supporting DLL children’s home language while discussing science. Finally, results indicate that teaching science supports children’s academic performance in several outcomes. These findings have implications for DLL education policy as science may be a domain where teachers can support children’s home language and their learning across multiple domains

IL23R (Interleukin 23 Receptor) variants protective against inflammatory bowel diseases (IBD) display loss of functiondue to impaired protein stability and intracellular trafficking

Genome-wide association studies as well as murine models have shown that the interleukin 23 receptor (IL23R) pathway plays a pivotal role in chronic inflammatory diseases such as Crohn disease (CD), ulcerative colitis, psoriasis, and type 1 diabetes. Genome-wide association studies and targeted re-sequencing studies have revealed the presence of multiple potentially causal variants of the IL23R. Specifically the G149R, V362I, and R381Q IL23R chain variants are linked to protection against the development of Crohn disease and ulcerative colitis in humans. Moreover, the exact mechanism of action of these receptor variants has not been elucidated. We show that all three of these IL23R variants cause a reduction in IL23 receptor activation-mediated phosphorylation of the signaltransducing activator of transcription 3 (STAT3) and phosphorylation of signal transducing activator of transcription 4 (STAT4). The reduction in signaling is due to lower levels of cell surface receptor expression. For G149R, the receptor retention in the endoplasmic reticulum is due to an impairment of receptor maturation, whereas the R381Q and V362I variants have reduced protein stability. Finally, we demonstrate that the endogenous expression of IL23R protein from V362I and R381Q variants in human lymphoblastoid cell lines exhibited lower expression levels relative to susceptibility alleles. Our results suggest a convergent cause of IL23R variant protection against chronic inflammatory disease

Targeting the absence: Homozygous DNA deletions as immutable signposts for cancer therapy

Many cancers harbor homozygous DNA deletions (HDs). In contrast to other attributes of cancer cells, their HDs are immutable features that cannot change during tumor progression or therapy. I describe an approach, termed deletion-specific targeting (DST), that employs HDs (not their effects on RNA/protein circuits, but deletions themselves) as the targets of cancer therapy. The DST strategy brings together both existing and new methodologies, including the ubiquitin fusion technique, the split-ubiquitin assay, zinc-finger DNA-recognizing proteins and split restriction nucleases. The DST strategy also employs a feedback mechanism that receives input from a circuit operating as a Boolean OR gate and involves the activation of split nucleases, which destroy DST vector in normal (nontarget) cells. The logic of DST makes possible an incremental and essentially unlimited increase in the selectivity of therapy. If DST strategy can be implemented in a clinical setting, it may prove to be curative and substantially free of side effects

Unravelling the mechanism of TrkA-induced cell death by macropinocytosis in medulloblastoma Daoy cells

Macropinocytosis is a normal cellular process by which cells internalize extracellular fluids and nutrients from their environment and is one strategy that Ras-transformed pancreatic cancer cells use to increase uptake of amino acids to meet the needs of rapid growth. Paradoxically, in non-Ras transformed medulloblastoma brain tumors, we have shown that expression and activation of the receptor tyrosine kinase TrkA overactivates macropinocytosis, resulting in the catastrophic disintegration of the cell membrane and in tumor cell death. The molecular basis of this uncontrolled form of macropinocytosis has not been previously understood. Here, we demonstrate that the overactivation of macropinocytosis is caused by the simultaneous activation of two TrkA-mediated pathways: (i) inhibition of RhoB via phosphorylation at Ser185 by casein kinase 1, which relieves actin stress fibers, and (ii) FRS2-scaffolded Src and H-Ras activation of RhoA, which stimulate actin reorganization and the formation of lamellipodia. Since catastrophic macropinocytosis results in brain tumor cell death, improved understanding of the mechanisms involved will facilitate future efforts to reprogram tumors, even those resistant to apoptosis, to die