Static and Dynamic Software Quality Metric Tools

The ability to detect and predict poor software quality is of major importance to software engineers, managers, and quality assurance organizations. Poor software quality leads to increased development costs and expensive maintenance. With so much attention on exacerbated budgetary constraints, a viable alternative is necessary. Software quality metrics are designed for this purpose. Metrics measure aspects of code or PDL representations, and can be collected and used throughout the life cycle [RAMC85]

Maia: A language for mandatory integrity controls of structured data

The integrity of systems files is necessary for the secure functioning of an operating system. Integrity is not generally discussed in terms of complete computer systems. Instead, integrity issues tend to be either tightly coupled to a particular domain (e.g. database constraints), or else so broad as to be useless except after the fact (e.g. backups). Often, file integrity is determined by who modifies the file or by a checksum. This paper focuses on a general model of the internal integrity of a file. Even if a file is modified by a subject with trust or has a valid checksum, it may not meet the specification of a valid file. An example would be a password file with no user assigned a user id of 0. In this paper, we describe a language called Maia that provides a means to specify what the contents of a valid file should be. Maia can be used to specify the format and valid properties of system configuration files, PNG files and others. We give a structural operational semantics of Ma ia and discuss an initial implementation within a mandatory integrity system

The promoter for intestinal cell kinase is head-to-head with F-Box 9 and contains functional sites for TCF7L2 and FOXA factors

<p>Abstract</p> <p>Background</p> <p>Intestinal cell kinase (ICK; GeneID 22858) is a conserved MAPK and CDK-like kinase that is widely expressed in human tissues. Data from the Cancer Genome Anatomy Project indicated ICK mRNA is increased in cancer, and that its expression correlated with expression of mRNA for an uncharacterized F-box protein, FBX9 (GeneID: 26268). <it>ICK </it>and <it>FBX9 </it>genes are arranged head-to-head on opposite strands, with start sites for transcription separated by ~3.3 kb. We hypothesized ICK and FBX9 are potentially important genes in cancer controlled by a bidirectional promoter.</p> <p>Results</p> <p>We assessed promoter activity of the intergenic region in both orientations in cancer cell lines derived from breast (AU565, SKBR3), colon (HCT-15, KM12), and stomach (AGS) cancers, as well as in embryonic human kidney (HEK293T) cells. The intergenic segment was active in both orientations in all of these lines, and ICK promoter activity was greater than FBX9 promoter activity. Results from deletions and truncations defined a minimal promoter for ICK, and revealed that repressors and enhancers differentially regulate ICK versus FBX9 promoter activity. The ICK promoter contains consensus motifs for several FOX-family transcription factors that align when mouse and human are compared using EMBOSS. FOXA1 and FOXA2 increase luciferase activity of a minimal promoter 10-20 fold in HEK293T cells. Consensus sites for TCF7L2 (TCF4) (Gene Id: 6934) are also present in both mouse and human. The expression of β-catenin increased activity of the minimal promoter ~10 fold. ICK reference mRNAs (NM_014920.3, NM_016513) are expressed in low copy number and increased in some breast cancers, using a ten base tag 5'-TCAACCTTAT-3' specific for both ICK transcripts.</p> <p>Conclusion</p> <p><it>ICK </it>and <it>FBX9 </it>are divergently transcribed from a bidirectional promoter that is GC-rich and contains a CpG island. A minimal promoter for <it>ICK </it>contains functional sites for β-cateinin/TCF7L2 and FOXA. These data are consistent with functions that have been proposed for ICK in development and in proliferation or survival of some breast and colon cancers.</p

A Grassroots Approach to Graduate Teaching Assistant Mentoring

Graduate students, whether master's or doctoral candidates, benefit greatly from their academic experiences. However, graduate school is not limited to course work and research, but it also includes teaching experiences as graduate teaching assistants (GTAs). Although GTAs are technically proficient in course materials, other factors can cause teaching experiences to go awry for them, their students, or the course supervisor. These factors arise out of a need for quality training on issues including pedagogy, interaction resolution, organizational concerns, and professional matters. This paper provides a grassroots approach to improve teachine techniques through GTA mentoring. GTAs are encouraged, with materials supplied here, to seek out and consult with more experienced GTAs who will serve as their mentors

Mechanism of an ATP-independent Protein Disaggregase. II. Distinct Molecular Interactions Drive Multiple Steps During Aggregate Disassembly

The ability of molecular chaperones to overcome the misfolding and aggregation of proteins is essential for the maintenance of proper protein homeostasis in all cells. Thus far, the best studied disaggregase systems are the Clp/Hsp100 family of “ATPases associated with various cellular activities” (AAA^+) ATPases, which use mechanical forces powered by ATP hydrolysis to remodel protein aggregates. An alternative system to disassemble large protein aggregates is provided by the 38-kDa subunit of the chloroplast signal recognition particle (cpSRP43), which uses binding energy with its substrate proteins to drive disaggregation. The mechanism of this novel chaperone remains unclear. Here, molecular genetics and structure-activity analyses show that the action of cpSRP43 can be dissected into two steps with distinct molecular requirements: (i) initial recognition, during which cpSRP43 binds specifically to a recognition motif displayed on the surface of the aggregate; and (ii) aggregate remodeling, during which highly adaptable binding interactions of cpSRP43 with hydrophobic transmembrane domains of the substrate protein compete with the packing interactions within the aggregate. This establishes a useful framework to understand the molecular mechanism by which binding interactions from a molecular chaperone can be used to overcome protein aggregates in the absence of external energy input from ATP

Psychological interventions for adults with bipolar disorder: a systematic review and meta-analysis

Background Psychological interventions may be beneficial for bipolar disorder. Aims Efficacy evaluation of psychological interventions for adults with bipolar disorder. Methods A systematic review of randomised controlled trials.. Outcomes were meta-analysed using RevMan and confidence assessed using the GRADE-method. Results We included 55 trials with 6010 participants. Moderate quality evidence associated individual psychological interventions with reduced relapses at post-treatment and follow-up, and collaborative care with a reduction in hospitalisations. . Low quality evidence associated group interventions with fewer depression relapses at post-treatment and follow-up, and family psycho-education with reduced symptoms of depression and mania at post-treatment. Conclusions There is evidence that psychological interventions are effective for people with bipolar disorder. Limits were the very low quality of much of the evidence and therefore inconclusive. Further research should identify the most (cost)-effective interventions for each phase of this disorder

Statistical competencies for medical research learners: What is fundamental?

IntroductionIt is increasingly essential for medical researchers to be literate in statistics, but the requisite degree of literacy is not the same for every statistical competency in translational research. Statistical competency can range from 'fundamental' (necessary for all) to 'specialized' (necessary for only some). In this study, we determine the degree to which each competency is fundamental or specialized.MethodsWe surveyed members of 4 professional organizations, targeting doctorally trained biostatisticians and epidemiologists who taught statistics to medical research learners in the past 5 years. Respondents rated 24 educational competencies on a 5-point Likert scale anchored by 'fundamental' and 'specialized.'ResultsThere were 112 responses. Nineteen of 24 competencies were fundamental. The competencies considered most fundamental were assessing sources of bias and variation (95%), recognizing one's own limits with regard to statistics (93%), identifying the strengths, and limitations of study designs (93%). The least endorsed items were meta-analysis (34%) and stopping rules (18%).ConclusionWe have identified the statistical competencies needed by all medical researchers. These competencies should be considered when designing statistical curricula for medical researchers and should inform which topics are taught in graduate programs and evidence-based medicine courses where learners need to read and understand the medical research literature

Nerve Agent Hydrolysis Activity Designed into a Human Drug Metabolism Enzyme

Organophosphorus (OP) nerve agents are potent suicide inhibitors of the essential neurotransmitter-regulating enzyme acetylcholinesterase. Due to their acute toxicity, there is significant interest in developing effective countermeasures to OP poisoning. Here we impart nerve agent hydrolysis activity into the human drug metabolism enzyme carboxylesterase 1. Using crystal structures of the target enzyme in complex with nerve agent as a guide, a pair of histidine and glutamic acid residues were designed proximal to the enzyme's native catalytic triad. The resultant variant protein demonstrated significantly increased rates of reactivation following exposure to sarin, soman, and cyclosarin. Importantly, the addition of these residues did not alter the high affinity binding of nerve agents to this protein. Thus, using two amino acid substitutions, a novel enzyme was created that efficiently converted a group of hemisubstrates, compounds that can start but not complete a reaction cycle, into bona fide substrates. Such approaches may lead to novel countermeasures for nerve agent poisoning