Search

ML-133 is a novel small molecule with potent antiproliferative activity, as shown in cancer cell lines and in a human colon tumor xenograft model. ML-133 reduces the concentration of intracellular labile zinc in HT-29 colon cancer cells, leading to induction of the Krüppel-like factor 4 transcription factor. Krüppel-like factor 4 displaces the positive regulator SP1 from the cyclin D1 promoter, thereby negatively regulating the expression of cyclin D1 and promoting the G1-S phase arrest of cell proliferation. The antiproliferative and antitumor activity of ML-133 described in the present study suggests modulation of intracellular zinc homeostasis as a potential strategy for the treatment of several cancer types, and ML-133 represents a promising new class of antitumor agents that deserves further development. [Mol Cancer Ther 2009;8(9):2586–96]

Supplementary Data from A novel small molecule with potent anticancer activity inhibits cell growth by modulating intracellular labile zinc homeostasis

AIM To evaluate the association between the image quality of cancer staging whole-body magnetic resonance imaging (WB-MRI) and patient demographics, distress, and perceived scan burden. MATERIALS AND METHODS A sample of patients recruited prospectively to multicentre trials comparing WB-MRI with standard scans for staging lung and colorectal cancer were invited to complete two questionnaires. The baseline questionnaire, administered at recruitment, collated data on demographics, distress and co-morbidity. The follow-up questionnaire, completed after staging investigations, measured perceived WB-MRI scan burden (scored 1 low to 7 high). WB-MRI anatomical coverage, and technical quality was graded by a radiographic technician and grading combined to categorise the scan as “optimal”, “sub-optimal” or “degraded”. A radiologist categorised 30 scans to test interobserver agreement. Data were analysed using the chi-square, Fisher's exact, t-tests, and multinomial regression. RESULTS One hundred and fourteen patients were included in the study (53 lung, 61 colorectal; average age 65.3 years, SD=11.8; 66 men [57.9%]). Overall, 45.6% (n=52), scans were classified as “optimal” quality, 39.5% (n=45) “sub-optimal”, and 14.9% (n=17) as “degraded”. In adjusted analyses, greater deprivation level and higher patient-reported scan burden were both associated with a higher likelihood of having a sub-optimal versus an optimal scan (odds ratio [OR]: 4.465, 95% confidence interval [CI]: 1.454 to 13.709, p=0.009; OR: 1.987, CI: 1.153 to 3.425, p=0.013, respectively). None of the variables predicted the likelihood of having a degraded scan. CONCLUSIONS Deprivation and patients' perceived experience of the WB-MRI are related to image quality. Tailored protocols and individualised patient management before and during WB-MRI may improve image quality.

Although it is often stated that the production of new knowledge is an intrinsically valuable objective, health science research is duty bound to show the public value of its work. However, a common criticism of empirical science is its failure of translation into society-useful outcomes. For example a common perception is that science is expert driven rather than society led, with little interaction between the two in the translation process. No more is this more important than in brain health, in which the public understanding is parsimonious. Within this context we review the key elements of research-based societal change and will present new models of knowledge transfer and impact, including the WHO knowledge transfer model for ageing and health, its application in real life settings and the example of the Global Council for Brain Health whose remit is the presentation of reliable public messages derived from expert evidence.

Load margin is a reasonable measure to quantify the bifurcation-related instability, defined as the amount of additional load on a specified pattern of load increase that would cause system instability. If the initial operating point and load increase pattern are specific, the stability margin is specific and can be obtained easily. If the initial operating point is random, the stability margin is also a random variable. This paper adopts a probabilistic eigenvalue method to determine the stability margin under load uncertainty. With the assumption of load being of normal distribution, the computed eigenvalues distribution is also close to normal distribution, but the stability margin distribution is irregular. An effective and systematic probabilistic approach to assess the probabilistic margin is proposed. Monte Carlo simulations consisting of 10,000 samples are used as a reference solution for evaluation of the accuracy of the proposed method. In addition, power system voltage stabilizer is adopted to improve the probabilistic stability margin by a proposed optimization technique. The proposed methods are investigated on two test systems.

Due to increasing number of controllers, sensors and actuators in conventional instrumentation systems, cabling connection complexity has also grown, increasing time and maintenance cost. As a result, the use of IEEE 802.15.4 standard in Wireless Sensors Networks (WSN) have also increased, allowing faster maintenance time, as well as layout changes. In some applications, where there are no reliable sources of energy, the aspect of energy consumption is very important, as in environmental monitoring, mobile applications, agricultural industry and automation of oil wells. This book chapter presents the mainly practices to reduce energy consumption in wireless sensor networks and new techniques. A few of the new power-saving techniques are the Dynamic Scaling Voltage that is a real time reduction of the supply voltage, the Dynamic Modulation Schedule that allows channel characteristics changes according to the need for energy economy, Rational Time Sampling that change the duty cycle of the device dynamically, and the most used and most economical network protocols. A design of an energy-efficient system is presented, show the hardware and software detail of subsystem and communications aspects, emphasizing the control subsystem of charge and discharge, for uses with a solar panels, as well as software optimized for task of network controlling and sensing, both characteristics that leads a reduced consumption of energy. This chapter also presents a consumption estimation method to be used in WSN designs projects that allows the engineer to define the network characteristics as a set of performance requirements and suggests further developments in this area.

In this work, it is shown that the similarities between discretized and continuum models of water are heavily dependent upon the exact value of the discretization parameter, ζ , defined as the ratio of the Lennard–Jones size parameter σ to the lattice spacing. For example, some discretized models layered into a hexagonal ice-like structure at temperatures up to 550 K. A discretization parameter of ζ = 13 was chosen such that the radial distribution function of the liquid at 298 K for the lattice model closely matched the continuum. This discretized model is capable of reproducing the low-temperature phase diagram with the advantage of significant CPU time savings.

The Gab family of docking proteins (Gab1 and Gab2) are phosphorylated in response to various cytokines and growth factors. Gab1 acts to diversify the signal downstream from the Met receptor tyrosine kinase through the recruitment of multiple signaling proteins, and is essential for epithelial morphogenesis. To determine whether Gab1 and Gab2 are functionally redundant, we have examined the role of Gab2 in epithelial cells. Both Gab1 and Gab2 are expressed in epithelial cells and localize to cell-cell junctions. However, whereas overexpression of Gab1 promotes a morphogenic response, the overexpression of Gab2 fails to induce this response. We show that Gab2 recruitment to the Met receptor is dependent on the Grb2 adapter protein. In contrast, Gab1 recruitment to Met is both Grb2 dependent and Grb2 independent. The latter requires a novel amino acid sequence present in the Met-binding domain of Gab1 but not Gab2. Mutation of these residues in Gab1 impairs both association with the Met receptor and the ability of Gab1 to promote a morphogenic response, whereas their insertion into Gab2 increases Gab2 association with Met, but does not confer on Gab2 the ability to promote epithelial morphogenesis. We propose that the Grb2-independent recruitment of Gab proteins to Met is necessary but not sufficient to promote epithelial morphogenesis.

As people live longer, the need for clear, trustworthy information on brain and cognitive health is greater than ever. Launched in 2015, the Global Council on Brain Health is an independent collaborative of scientists, clinicians, scholars and policy experts convened by AARP to provide the foremost thinking on what people and professionals can do to maintain and improve brain health. The goal of the Council is to translate scientific research into actionable recommendations for the public that will help drive behavior change in individuals across communities and cultures. This symposium will feature leading researchers from the UK, US and Canada to highlight recommendations issued by the Council. It will showcase three consensus documents generated by the Council that are based on the latest research advancements. Particular emphasis will be placed on Council recommendations that are aimed at improving brain health in three areas: physical exercise, sleep and social engagement. In sum, this symposium brings together leaders at the forefront of this international effort to discuss the scientific and policy dimensions of brain health.

We present a new teaching and outreach activity based around the construction of a three-dimensional chart of isotopes using LEGO$^{\circledR}$ bricks. The activity, \emph{Binding Blocks}, demonstrates nuclear and astrophysical processes through a seven-meter chart of all nuclear isotopes, built from over 26,000 LEGO$^{\circledR}$ bricks. It integrates A-level and GCSE curricula across areas of nuclear physics, astrophysics, and chemistry, including: nuclear decays (through the colours in the chart); nuclear binding energy (through tower heights); production of chemical elements in the cosmos; fusion processes in stars and fusion energy on Earth; as well as links to medical physics, particularly diagnostics and radiotherapy., Minor changes

This purpose of this paper is to explore the intersecrion of gender, equity and the discourse of diversity. The authors argue that while the goal of diversity in a democratic society is an admirable one, its advocacy could limit any real educational change. To explore the differences between the discourse of diversity and language of equity, they draw upon two action research studies conducted by two elementary school reachers who were not elementary physical education specialists. Through their action research projects, which included direct instruction as a way to confront the gender discrimination that was occurring in the physical education component of their classrooms, these teachers found that they had to abandon the discourse of diversity and embrace the language of equity for meaningful educational change to occur.

With gross income of £16bn and assests of over £35bn the charity sector is an important part of the economy but how efficient is the Charity Commision at regulating its activity? This article studies two high profile investigations performed by the Commision (War on Want and Oxfam) and asks whether the Commission was forced to react to adverse public comment by launching inquiries it did not want. Adverse reports into the activities of the Charity Commision have resulted in better monitoring procedures and the recruitment of qualified accountants. In addition the increasing diversification of the activities of the charity sector is bringing regulation by other forces, will these be any more effective? In a sector depending on public support another failure could cause serious problems.

College women's perceptions about resistance to sexual assault were examined. Twenty-one percent of the 334 women surveyed stated that they had been sexually assaulted. The vast majority of participants had changed their lifestyles to prevent a sexual assault. Less than 1 woman in 5 of those surveyed had taken a self-defense class. Participants believed that resisting sexual assault by a stranger with a weapon was more likely than resisting an unarmed attacker to increase their chances of being physically harmed, raped, or murdered. Twenty-two percent of the participants said they were "very likely" to resist sexual assault by a stranger with a weapon; 52% would resist a stranger without a weapon. The findings indicate the need for an increase in the number of women taking self-defense classes and a revision in women's perceptions about resisting sexual assault.

Rice necrosis mosaic virus (RNMV) has physico-chemical and biological properties typical of the Bymovirus genus. However, to date no sequence data has been reported for RNMV. In this paper we report the use of a PCR primer, designed from an area of high homology between bymoviruses and related macluraviruses within the NIb gene, which generated a 1.4kb fragment from the 3' terminal region of RNA 1 of RNMV. The sequence data generated from this region confirmed the classification of RNMV as a member of the Bymovirus genus.

A commercial method for N-acetyl-β-glucosaminidase (NAG) is described for use on a discrete analyser. Timed overnight urine was obtained from 20 healthy volunteers and 60 Type I diabetic patients for estimation of NAG (expressed in relation to creatinine) and albumin excretion rate (AER). The upper reference limit for NAG excretion in the control patients was found to be 0·25 U/mmol creatinine but was abnormally raised in 60% of Type I diabetic patients before any increase in AER (greater than 20 μg/min), and in 82% of patients with AER greater than 200 μg/min. A positive correlation was found between NAG excretion and AER in Type I diabetes ( r = 0·61, p < 0·01), but not with glycaemic control as measured by serum fructosamine levels. We conclude that measurement of NAG excretion in diabetes indicates renal tubular dysfunction or damage before any significant change in albumin excretion rate.

The purpose of the paper was to review the physical education literature in selected journals with regard to women’s issues. The review was inclusive of the years 1972 to 1991 and focused on five prominent publications in physical education: Research Quarterly, a journal which presents current research in the different knowledge base areas in physical education (exercise physiology, biomechanics, sport pedagogy, etc.); The Journal of Physical Education Recreation & Dance, a journal which features articles for the practitioner in physical education; Quest, a journal which is a publication of an association of physical educators in higher education; The Journal of Teaching in Physical Education, which focuses on pedagogy in physical education; and The Physical Educator, a journal which is a publication of Phi Epsilon Kappa, a fraternal organization in physical education.

BACKGROUND--Crackles are a prominent clinical feature of asbestosis and may be an early sign of the condition. Auscultation, however, is subjective and interexaminer disagreement is a problem. Computerised lung sound analysis can visualise, store, and analyse lung sounds and disagreement on the presence of crackles is minimal. High resolution computed tomography (HRCT) is superior to chest radiography in detecting early signs of asbestosis. The aim of this study was to compare clinical auscultation, time expanded wave form analysis (TEW), chest radiography, and HRCT in detecting signs of asbestosis in asbestos workers. METHODS--Fifty three asbestos workers (51 men and two women) were investigated. Chest radiography and HRCT were assessed by two independent readers for detection of interstitial opacities. HRCT was performed in the supine position with additional sections at the bases in the prone position. Auscultation for persistent fine inspiratory crackles was performed by two independent examiners unacquainted with the diagnosis. TEW analysis was obtained from a 33 second recording of lung sounds over the lung bases. TEW and auscultation were performed in a control group of 13 subjects who had a normal chest radiograph. There were 10 current smokers and three previous smokers. In asbestos workers the extent of pulmonary opacities on the chest radiograph was scored according to the International Labour Office (ILO) scale. Patients were divided into two groups: 21 patients in whom the chest radiograph was > 1/0 (group 1) and 32 patients in whom the chest radiograph was scored < or = 1/0 (group 2) on the ILO scale. RESULTS--In patients with an ILO score of < or = 1/0 repetitive mid to late inspiratory crackles were detected by auscultation in seven (22%) patients and by TEW in 14 (44%). HRCT detected definite interstitial opacities in 11 (34%) and gravity dependent subpleural lines in two (6%) patients. All but two patients with evidence of interstitial disease or gravity dependent subpleural lines on HRCT had crackles detected by TEW. In patients with an ILO score of > 1/0 auscultation and TEW revealed mid to late inspiratory crackles in all patients, whereas HRCT revealed gravity dependent subpleural lines in one patient and signs of definite interstitial fibrosis in the rest. In normal subjects crackles different from those detected in asbestosis were detected by TEW in three subjects but only in one subject by auscultation. These were early, fine inspiratory crackles. CONCLUSION--Mid to late inspiratory crackles in asbestos workers are detected by TEW more frequently than by auscultation. Signs of early asbestosis not apparent on the plain radiograph are detected by TEW and HRCT with similar frequency. off

This paper proposes a clamping phase technique that results in power factor control at the input of a controlled rectifier by means of a current control based on One Cycle Control (OCC) technique. It minimizes phase interference, fixes operation frequency as well as improves phase coordination. Control simplicity and voltage input sensor elimination is the feature of the proposed control. Theoretical background of the clamping phase technique as well as of OCC principle has been reviewed and analyzed. Simulated results confirm the proposed technique.

This paper describes the design, development, testing and performance of the Ball Aerospace & Technologies Corp. SB235E, a 2-stage long life space cryocooler optimized for 2 cooling loads. The SB235E model is designed to provide simultaneous cooling at 35 K (typically for HgCdTe detectors) and 85 K (typically for optics). The SB235E is a higher capacity model derivative of the SB235. Initial testing of the SB235E has shown performance of 2.13 W at 35 K and 8.14 W at 85 K for 200 W power at 289 K rejection temperature. These data equate to Carnot efficiency of 0.175 or nearly twice that of other published space cryocooler data. Qualification testing has been completed including full performance mapping and vibration export. Performance mapping with the cold-stage temperature varying from 20 K to 80 K and mid-stage temperature varying from 85 K to 175 K are presented. Two engineering models of the SB235E are currently in build.

This paper describes the design, development, testing, and performance at Ball Aerospace of a long-life hybrid (combination of Stirling and Joule-Thomson [J-T] thermodynamic cycles) space cryocooler. Hybrid coolers are synergistic combinations of two thermodynamic cycles that combine advantages of each cycle to yield overall improved performance. Hybrid cooler performance advantages include: 1) load leveling of large heat loads; 2) remote cryogenic cooling with very low to negligible induced vibration and jitter; 3) very low redundant (off state) cooler penalties; 4) high power efficiency, especially at low temperatures; and 5) simplified system integration with capability to cross gimbals and no need for thermal straps or switches.Ball Aerospace is currently developing several different hybrid cooler systems. The 35 K hybrid cooler provides 2.0 W at 35 K and 8.5 W at 85 K with an emphasis on load leveling of high transient heat loads and remote, low vibration cooling. The 10 K hybrid cooler provides 200 ...

The modified Harvard Step Test and a 70-item questionnaire based on the Health Belief Model (HBM) were given to 257 high school students, 154 blacks, and 93 whites. Mean age of students was 16.0 years (SD = 1.1) for whites and 15.8 years (SD = 1.1) for blacks. Though more blacks than whites were in poor physical condition (51% females and 27% males vs. 35% females and 16% males, respectively), the difference was not statistically significant. A high level of concurrence existed between individuals in good physical condition and those who stated they regularly exercised, but this agreement was more pronounced among white students (73% vs. 62% for black students). White students were significantly more knowledgeable than black students on the exercise knowledge subscale. No significant differences existed between black and white students on any other HBM subscales. When subscale scores for those in good versus poor physical condition were compared, significant differences were found on all subscales except the perceived benefits subscale. Analysis of individual questionnaire items which best predicted whether one was in poor or good physical condition found four items accounted for 38% of variance in black students, and seven items accounted for 52% of variance in white students.

International audience; The synthesis of rotaxanes derived from the synthetic peptide macrocycles cyclo(l-ProGly)4 and cyclo(l-ProGly)5 and diammonium threads is described. [2]Rotaxanes are formed in good yields (56-63%), despite the disruption of internal amide-amide hydrogen bonding in the macrocycles.

The purpose of this study was to determine if high school females differed in individual measures of health-related physical fitness, barriers to exercise, or activity level based on ethnicity or socioeconomic status. A cross-sectional sample consisting of African American (28%), Hispanic (23%), and white (49%) female high school students, 46% from low socioeconomic groups and 54% from moderate or high socioeconomic groups (n = 1314, age = 16.2 ± 0.9) participated in this study. A 15-question survey instrument assessed barriers to exercise and activity level. The FITNESSGRAM fitness test assessed aerobic capacity and body mass index (BMI), and skinfold calipers were used to assess percent body fat. Significant differences between African Americans, Hispanics, and whites were found on the following dependent variables: BMI, percent fat, mile run, perceived barriers to exercise, and activity level. Significant differences between socioeconomic groups were found on the following dependent variables: percent fat, mile run, activity level, and perceived barriers to exercise. These results suggest that students of minority and low socioeconomic groups should be given separate and different interventions regarding health-related fitness. (J Sch Health. 2006;76(1):12-17)

This paper describes the HIRDLS (High Resolution Dynamic Limb Sounder) Cryocooler Subsystem (CSS) and its on‐orbit flight performance. The HIRDLS Instrument was launched on July 15, 2004 as part of the NASA GSFC EOS Aura platform. Ball Aerospace provided the CSS, which includes the long life Stirling cryocooler (cooling at 59 K), cold plumbing to connect the cooler to the instrument Detector Subsystem, an ambient radiator to reject the cooler dissipation, and a vacuum enclosure system that enabled bench top ground testing. As of August 20, 2005, the cryocooler has over 9,000 hours of continuous operation with performance that exceeds requirements. Of note is that the CSS has experienced virtually no change in performance, including no indication of external contamination related degradation that has been evident on several other cryocooler systems in space flights. This steady performance can be attributed to the multi‐layer insulation (MLI) based insulation design, which will be described in the paper.

The students in this course are typically near the end of their professional education sequence, so most have had numerous field experiences. In addition, these physical education majors are not new to me nor I to them, since I have had all of them in a number of other courses. The interesting and unique characteristic of this particular group was that the students were all able-bodied white males. My intention was to bring these 11 young men to the point of being able to genuinely reflect upon their own teaching in such a way as to make meaningful changes in how they perceived their role as teachers. I wanted them to engage in liberatory practice in the gymnasium.

The preparation of 6(A)-deoxy-6(A)-(6-(2-(1,4,7,10-tetraoxa-13-azacyclopentadecan-13-yl)acetamido)hexylamino)-alpha-cyclodextrin, 3, 6(A)-deoxy-6(A)-(6-(2-(1,4,7,10,13-pentaoxa-16-azacyclooctadecan-16-yl)acetamido)hexylamino)-alpha-cyclodextrin, 4, and their beta-cyclodextrin analogues, 5 and 6, are described. (1)H (600 MHz) ROESY NMR spectra of the C(6) substituted beta-cyclodextrins, 5 and 6, are consistent with the intramolecular complexation of their azacyclopentadecanyl- and azacyclooctadecanyl(acetamido)hexylamino substituents in the beta-cyclodextrin annulus in D(2)O at pD = 8.5 whereas those of their alpha-cyclodextrin analogues, 3 and 4 are not complexed in the alpha-cyclodextrin annulus. This is attributed to the monoazacoronand components of the substituents being able to pass through the beta-cyclodextrin annulus whereas they are too large to pass through the alpha-cyclodextrin annulus. However, the substituents of 3 and 4 are intermolecularly complexed by beta-cyclodextrin to form pseudo [2]-rotaxanes. Metallocyclodextrins are formed by 5 through complexation by the monoazacoronand substituent component for which log (K/dm(3) mol(-1))=2, 6.34 and 5.38 for Ca(2+), Zn(2+) and La(3+), respectively, in aqueous solution at 298.2 K and I= 0.10 mol dm(-3)(NEt(4)ClO(4)).

The Gab1 docking protein forms a platform for the assembly of a multiprotein signaling complex downstream from receptor tyrosine kinases. In general, recruitment of Gab1 occurs indirectly, via the adapter protein Grb2. In addition, Gab1 interacts with the Met/hepatocyte growth factor receptor in a Grb2-independent manner. This interaction requires a Met binding domain (MBD) in Gab1 and is essential for Met-mediated epithelial morphogenesis. The Gab1 MBD has been proposed to act as a phosphotyrosine binding domain that binds Tyr-1349 in the Met receptor. We show that a 16-amino acid motif within the Gab1 MBD is sufficient for interaction with the Met receptor, suggesting that it is unlikely that the Gab1 MBD forms a structured domain. Alternatively, the structural integrity of the Met receptor, and residues upstream of Tyr-1349 located in the C-terminal lobe of the kinase domain, are required for Grb2-independent interaction with the Gab1 MBD. Moreover, the substitution of Tyr-1349 with an acidic residue allows for the recruitment of the Gab1 MBD and for phosphorylation of Gab1. We propose that Gab1 and the Met receptor interact in a novel manner, such that the activated kinase domain of Met and the negative charge of phosphotyrosine 1349 engage the Gab1 MBD as an extended peptide ligand.

We assessed the feasibility of a remote monitoring system for asthmatic patients to use in their own homes. Eighty-four patients were invited to participate following discharge from hospital after an acute exacerbation of their asthma. We remotely monitored 33 patients from two hospitals for two weeks. Their mean age was 34 years (range 17–50 years). Patient compliance with monitoring was 80% (range 45–231%) and compliance with transmitting the results using a modem was 52% (range 0–100%). The average time spent teaching patients how to perform measurements was 16 min (range 2–55 min) and time spent providing asthma education was 39 min (range 5–135 min). Ninety-six per cent of patients found the equipment easy or very easy to use and 92% said they would use the equipment again in the future. Medical intervention occurred in 48% of patients during the study period, which suggests that the use of remote monitoring could be important in reducing asthma morbidity and improving treatment outcomes.

The Gab family of docking proteins is phosphorylated in response to various growth factors and cytokines and serves to recruit multiple signaling proteins. Gab1 acts downstream from the Met-hepatocyte growth factor receptor, and Gab1 overexpression promotes Met-dependent morphogenesis of epithelial cells. Recruitment of Gab1 to Met or epidermal growth factor (EGF) receptors requires a receptor-binding site for the Grb2 adapter protein and a proline-rich domain in Gab1, defined as the Met-binding domain. To determine the requirement for Grb2 in Gab1 recruitment, we have mapped two Grb2 carboxyl-terminal SH3 domain binding sites conserved in Gab1 and related protein Gab2. One corresponds to a canonical Grb2-binding motif, whereas the second, located within the Gab1 Met-binding domain, requires the proline and arginine residues of an atypical PXXXR motif. The PXXXR motif is required but not sufficient for Grb2 binding, whereas an extended motif, PX3RX2KPX7PLD, conserved in Gab proteins as well as the Grb2/Gads-docking protein, Slp-76, efficiently competes binding of Grb2 or Gads adapter proteins. The association of Gab1 with Grb2 is required for Gab1 recruitment to the EGF receptor but not the Met receptor. Hence different mechanisms of Gab1 recruitment may reflect the distinct biological functions for Gab1 downstream from the EGF and Met receptors.

A substantial portion of patients with estrogen receptor-positive breast cancer fail to respond to estrogen depletion or to the antiestrogen tamoxifen. The molecular changes that lead to tamoxifen resistance and estrogen-independent growth are unknown. To test the hypothesis that a p53 mutation could result in tamoxifen resistance and estrogen-independent growth, the MCF-7 cell line was transfected with p53 cDNA which was mutated at codon 179 (histidine to glutamine). MCF-7 is an estrogen receptor-positive, estrogen-dependent, tamoxifen-sensitive cell line with only wild-type p53. The presence of transfected mutant p53 cDNA was verified by the PCR, and overexpression of p53 protein was assessed by Western blotting. Five separate mutant-transfected clones were selected and tested in subsequent growth experiments. In monolayer culture, there was no consistent evidence of estrogen-independent growth or tamoxifen resistance in the mutant transfectants compared with vector-only controls or the parental cell line. In soft agar growth experiments, four of five mutant transfectants remained sensitive to tamoxifen in a dose-dependent manner. In the presence of wild-type p53, mutant 179 p53 protein does not result in estrogen-independent growth or tamoxifen resistance. These results do not exclude the possibility that other p53 mutational types could result in tamoxifen resistance, or that loss of the remaining wild-type allele may be necessary to result in this phenotype.

The purpose was to describe the characteristics of elementary school principals who support elementary physical education programs. A statewide random sample of 500 elementary school principals and their respective elementary physical education teachers ( n = 500) were mailed questionnaires. A total of 321 principals responded (64%) to a 20-item questionnaire which assessed their physical fitness and their perceptions of elementary physical education. A total of 340 physical education teachers (68%) responded to a 23-item survey assessing their perceptions of their elementary principals' support for the physical education program. The majority of teachers perceived their principals to be supportive of them and the physical education program. A series of l tests showed no significant differences in principals' age, gender, years of experience as a principal, or how important they thought health and physical education was compared to other subjects taught in the elementary school and how supportive of physical education the principals were perceived to be. Finally, a stepwise backward multiple regression analysis indicated that seven variables, including fitness of the principal and body mass index, did not explain more than 13% of the variance in teachers' perceived support by principals.