A quantitative comparison of corrective and perfective maintenance

This paper presents a quantitative comparison of corrective and perfective software maintenance activities. The comparison utilizes basic data collected throughout the maintenance process. The data collected are extensive and allow the impact of both types of maintenance to be quantitatively evaluated and compared. Basic statistical techniques test relationships between and among process and product data. The results show interesting similarities and important differences in both process and product characteristics

A study of transcription factors STAT3, SP1 and NFkB in breast cancer

Background and Aims: Breast cancer is the second most common cause of cancer deaths in women. It is a tumour which has been extensively studied at a molecular level and, compared to other solid tissue tumours, our understanding of its biology is extensive. There are however some patients who are considered to have good prognostic feature of their tumours who go on to die from their disease. Transcription factors are the end point of many cell signalling pathways. They form the link between exogenous hormones and growth factors and DNA transcription. For the purpose of this study 3 different transcription factors have been selected for investigation. STAT3 is activated by various growth factors and cytokines including EGF. It is classified as an oncoprotein as its activation can mediate tumorgenisis in nude mice. STAT3 has been shown to confer resistance to apoptosis in breast cancer cells and it is associated with poor outcome in high risk breast cancers. SP1 is a transcription factor which is essential in the expression and the action of estrogen receptors (ER). It is known to be over expressed in other solid tissue tumours but there has been little work into its role in breast cancer. NFkB is activated in many cell survival settings. It is involved in the transcription of anti-apoptotic genes and also plays a role in cell proliferation, angiogenisis and cell adhesion. It is associated in breast cancers with an over expression of the oncogene Bcl-2. It has not been show to be a marker of prognosis but does appear to identify breast cancers with a poor response to chemotherapy. The aim of this study is to investigate the role of these transcription factors in the behaviour of breast cancers and the outcome of the disease. It will also investigate the affect of EGF and estogen stimulation on STAT3 activation in breast cancer cell lines. Methods: This study consists of 2 elements. Firstly an assessment of transcription factor expression in breast cancer samples and secondly a cell model experiment to investigate the stimulation of STAT3 activation. A cohort of 213 patients who presented to the Queen Elizabeth Hospital with invasive breast cancer in 1999 was selected. Tumour samples from these patients were retrieved and using immunohistochemistry were tested for the expression of STAT3, SP1 and NFkB. These results were then correlated with pathological features of the tumours, tumour receptor status (ER, PR HER2 and EGFR) and outcome of the disease. Two cell lines, MCF7 and SKBr3, were cultured in depleted medium. These cells were then stimulated with estrogen and EGF alone and in combination. Flow-cytometry was then used to quantify the levels of phosphorylated STAT3 in the 2 cell lines over a 3 day time course. The level of phosphorylation was then compared to the control lines to asses the effect of stimulation. Results: 209 breast cancers were successfully analysed for the expression of STAT3, 27% of these cancers expressed nuclear STAT3. The results demonstrated a significant correlation of STAT3 expression with cancers of a high grade (p=2yr) disease recurrence (p=0.005). NFkB was over expressed in 15% of the 208 cancers samples. Again a significant correlation was shown with high grade tumours (p=0.001) and large tumours (p=0.014). NFkB expression was also shown to be more prevalent in ER negative cancers (p=0.006) and EGFR positive tumours (p=0.007). There was no significant relationship between NFkB expression and disease outcome. The cell model results showed that in the EGFR positive ER negative cell line (SKBr3), EGF stimulation resulted in a biphasic response of STAT3 phosphorylation, whereas estrogen had no effect on phosphorylation. In the ER positive MCF7 cells, which express low levels of EGFR, again EGF stimulation resulted in a biphasic response curve. Estrogen stimulation does cause an increase in activation but when estrogen is added to EGF stimulation there is an inhibition of STAT3 phosphorylation. Conclusions: This study has demonstrated that STAT3 and SP1 expression is important in disease outcome in breast cancer patients. Though there are differences in levels of expression, NFkB does not appear to have a role in breast cancer outcome. The cell model has show that EGF stimulation of EGFR positive cell lines results in increased STAT3 activation and also that this effect is inhibited by the addition of estrogen stimulation. These results raise important questions which are discussed in the study and suggest areas for further investigation.EThOS - Electronic Theses Online ServiceWomen's Cancer Detection SocietyGBUnited Kingdo

A comparison of reinforcement and model-reinforcement techniques in influencing verbal participation

The purpose of this study was to compare reinforcement and model-reinforcement techniques in increasing students' classroom verbal participation. Primary hypotheses to be investigated were: (1) there is no significant difference between model-reinforcement and reinforcement groups' adjusted posttest frequency of responding in the small group; and (2) there is no significant difference between model-reinforcement and reinforcement groups' adjusted posttest frequency of responding in class

Passive Laser Power Stabilization via an Optical Spring

Metrology experiments can be limited by the noise produced by the laser involved via small fluctuations in the laser's power or frequency. Typically, active power stabilization schemes consisting of an in-loop sensor and a feedback control loop are employed. Those schemes are fundamentally limited by shot noise coupling at the in-loop sensor. In this letter we propose to use the optical spring effect to passively stabilize the classical power fluctuations of a laser beam. In a proof of principle experiment, we show that the relative power noise of the laser is stabilized from approximately $2 \times 10^{-5}$ Hz$^{-1/2}$ to a minimum value of $1.6 \times 10^{-7}$ Hz$^{-1/2}$, corresponding to the power noise reduction by a factor of $125$. The bandwidth at which stabilization occurs ranges from $400$ Hz to $100$ kHz. The work reported in this letter further paves the way for high power laser stability techniques which could be implemented in optomechanical experiments and in gravitational wave detectors

Uropathic Observations in Mice Expressing a Constitutively Active Point Mutation in the 5-HT_(3A) Receptor Subunit

Mutant mice with a hypersensitive serotonin (5-HT)_(3A) receptor were generated through targeted exon replacement. A valine to serine mutation (V13′S) in the channel-lining M2 domain of the 5-HT_(3A) receptor subunit rendered the 5-HT₃ receptor ∼70-fold more sensitive to serotonin and produced constitutive activity when combined with the 5-HT_(3B) subunit. Mice homozygous for the mutant allele (5-HT_(3A)^(vs/vs)) had decreased levels of 5-HT_(3A) mRNA. Measurements on sympathetic ganglion cells in these mice showed that whole-cell serotonin responses were reduced, and that the remaining 5-HT₃ receptors were hypersensitive. Male 5-HT_(3A)^(vs/vs) mice died at 2-3 months of age, and heterozygous (5-HT_(3A)^(vs/+)) males and homozygous mutant females died at 4-6 months of age from an obstructive uropathy. Both male and female 5-HT_(3A) mutant mice had urinary bladder mucosal and smooth muscle hyperplasia and hypertrophy, whereas male mutant mice had additional prostatic smooth muscle and urethral hyperplasia. 5-HT_(3A) mutant mice had marked voiding dysfunction characterized by a loss of micturition contractions with overflow incontinence. Detrusor strips from 5-HT_(3A)^(vs/vs) mice failed to contract to neurogenic stimulation, despite overall normal responses to a cholinergic agonist, suggestive of altered neuronal signaling in mutant mouse bladders. Consistent with this hypothesis, decreased nerve fiber immunoreactivity was observed in the urinary bladders of 5-HT_(3A)^(vs/vs) compared with 5-HT_(3A) wild-type (5-HT_(3A)^(+/+)) mice. These data suggest that persistent activation of the hypersensitive and constitutively active 5-HT_(3A) receptor in vivo may lead to excitotoxic neuronal cell death and functional changes in the urinary bladder, resulting in bladder hyperdistension, urinary retention, and overflow incontinence

Testing for Near and Far Transfer Effects with a Short, Face-to-Face Adaptive Working Memory Training Intervention in Typical Children

A relatively quick, face-to-face, adaptive working memory training intervention was assessed in 5- to 8-year-old typically developing children, randomly allocated to a six-week intervention condition, or an active control condition. All children received 18 sessions of 10 minutes, three times/week for six weeks. Assessments of six working memory skills, word reading and mathematics were administered at pre-test, post-test, and six month follow-up. Additional measures of word reading, mathematics, spelling and reading comprehension were given at a 12 month follow-up. At post-test, the trained group showed significantly larger gains than the control group on the two trained executive-loaded working memory tasks (Listening Recall, Odd One Out Span) and on two untrained working memory tasks (Word Recall, Counting Recall). These "near transfer" effects were still apparent at six month follow-up. "Far transfer" effects were less evident: there was no difference between the groups in their gains on single word reading and mathematics over 12 months, and spelling skills did not differ at 12 month follow-up. However, the trained group showed significantly higher reading comprehension scores than the control group at 12 month follow-up. Thus, improving the ability to divide attention between processing and storage may have had specific benefits for reading comprehension