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Multiple Antibiotic Resistance (MAR) analysis and regression modeling techniques were used to identify surface water areas impacted by fecal pollution from human sources, and to determine the effects of land use on fecal pollution in Murrells Inlet, a small, urbanized, high-salinity estuary located between Myrtle Beach and Georgetown, South Carolina, MAR analysis was performed to identify areas in the estuary that are impacted by human-source fecal pollution. Additionally, regression analysis was performed to determine if an association exists between land use and fecal coliform densities over the ten-year period from 1989 to 1998. Land-use variables were derived using Geographic Information System (GIS) techniques and were used in the regression analysis. MAR analyses were conducted by comparing the frequency and patterns of antibiotic resistance found in Escherichia coli isolates derived from surface water samples and from sewage sources in the Murrells Inlet sewage collection system. The MAR results suggest that the majority of the fecal pollution detected in the Murrells Inlet estuary may be from non-human sources, including fecal coliforms isolated from areas in close proximity to high densities of active septic tanks. A MAR Index, which measures the frequency of antibiotic resistance, was calculated for each of twenty-three water samples and nine sewage samples. The antibiotic resistance pattern comparisons were performed using cluster analysis. Although the MAR indices indicated that several surface water sites had potential human-source contamination, the cluster analysis suggests that only one sampling site had MAR patterns that were similar to those found in the sewage samples. This site was in close proximity to several large pleasure boats as well as a sewage collection system lift station, but was not near areas with active septic tanks. The results of the regression analysis also suggest that sewage sources and rainfall runoff from urbanized areas may contribute to fecal pollution in the estuary.

Recent research has shown that after spinal cord injury, the nervous system reorganizes. Nevertheless, little is known of the effects of neural reorganization, or plasticity, on motor skills. In this work, we present a method that utilizes kinetic and kinematic analysis, for investigating balance control in a rodent model of incomplete spinal cord injury. In this setup, the animals sit unconstrained on their hindlimbs on a platform while they eat a Fruitloop. In this posture, the animal is supporting all the body weight on its hindquarters removing the need for the animal to support itself on its hindlimb or maintain appropriate forelimb-hindlimb coordination for functional gait. The platform is bolted to a force transducer to provide measurements of shear forces in orthogonal directions in the horizontal plane. Reflective markers on the hip and tail of the animal indicate sway of the animals body. Using this method the effect of extensive 12 week long treadmill locomotor training on balance control in rodents with incomplete thoracic spinal cord contusion injury (iSCI) was assessed. One iSCI rat did not undergo training, while a sham injured and 3 other iSCI rats underwent training. The shear forces and sway produced by the injured untrained rat were much larger than for the sham or the injured but trained rats. Stance width assessed from overground walking in a separate study was also larger in the injured untrained rat. These data suggest that balance control may be improved by a locomotor training paradigm. This simple method for assessing balance control could thus be utilized in longitudinal studies to evaluate the effectiveness of pharmacological and locomotor therapies for repair and recovery after spinal cord injury.

There is debate about whether New Zealand practices for teaching reading should include “more phonics”. With the focus on the first two years of school instruction, the status quo of receptive phonics and the teaching culture in which it is embedded are described and compared with the productive phonics practices of other teaching cultures. The response of New Zealand children to this practice is relatively faster reading procedures. However, there is much that remains to be learnt to sharpen New Zealand receptive phonics teaching practices to meet the successive developmental purposes of phonics; and also to reduce repetitive teaching rituals, as in practices to prompt for meaning.

B570 Centrosomal Clustering: A Novel Therapeutic Target for Multiple Myeloma MS Raab, I Breitkreutz, B Rebacz, PJ Hayden, TO Larsen, MH Clausen, JH Fruehauf, H Goldschmidt, KC Anderson, A Kraemer Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; CCU Molecular Hematology/ Oncology, German Cancer Research Center, Heidelberg, Germany; BioCentrum, Technical University of Denmark, Kopenhagen, Denmark; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; National Center of Tumor Diseases, Dept. of Medicine, University of Heidelberg, Germany

This is a report of an occupational survey of the Survival, Evasion, Resistance, and Escape Training (SERE) career ladder conducted by the Air Force Occupational Measurement Squadron (AFOMS). The current SERE career ladder was created in October 1993 with the conversion from AFSC 121X0 to AFSC 1T0X1. Survey data will be used to identify current utilization patterns among career ladder personnel and evaluate career ladder documents and training programs. The last OSR for the SERE career ladder was published in November 1992.

Teaching has two principal aspects: the motivational and informational. The motivational aspect is concerned, for example, with promoting the learner’s security and commitment to learning. The informational aspect is concerned with fostering the learner’s knowledge and skill. This review of the teaching of reading considers the second aspect and offers historical and international perspectives on selected current research. The emphasis is on teaching normal progress children during the initial years of primary schooling. The influences of the family and society are considered elsewhere in this volume, as also are children’s reading difficulties.

In the years ahead the determining influence of the British Parliament and courts on abortion law is expected to be superseded by intervention on the part of the European Convention on Human Rights. The major role of British courts has been to interpret the abortion law of 1967 including its balance test that requires judges to weigh whether continuation of a given pregnancy involves greater risks than terminations. Such rulings have relied more on consultation with medical professionals than on political factors. Judges are reluctant to challenge the need for abortion once this has been established by two medical practitioners per requirements of the 1967 Abortion Act. The European Convention calls for an investigation of complaints that a state has breached fundamental civil and political rights. The Convention does not include a clear statement on abortion but did vote against an injunction voted in the Irish courts that restrained abortion counselors from assisting pregnant Irish women to travel abroad to seek abortion. The Convention has been more bold rejecting husbands claims to be consulted about abortion and giving the right to life and health of the mother precedence over fetal rights. The Commission has left unclarified however the conditions under which a fetus does not have a right to life. Since the abortion issue has become conceptualized in terms of the competing rights of the woman and the fetus compromise is difficult to achieve. Greater resort to litigation before European institutions is expected a phenomenon that may force Britain to reassess its abortion policies and diminish the power of the British Parliament and courts in determining the conditions under which abortion is permissible.

Multiple myeloma (MM), the second most common hematological malignancy, initiates from a single site and spreads via circulation to multiple sites in the bone marrow (BM). Methods to track MM cells both in the BM and circulation would be useful for developing new therapeutic strategies to target MM cell spread. We describe the use of complementary optical techniques to track human MM cells expressing both bioluminescent and fluorescent reporters in a mouse xenograft model. Long-term tumor growth and response to therapy are monitored using bioluminescence imaging (BLI), while numbers of circulating tumor cells are detected by in-vivo flow cytometry. Intravital microscopy is used to detect early seeding of MM cells to the BM, as well as residual cancer cells that remain in the BM after the bulk of the tumor is eradicated following drug treatment. Thus, intravital microscopy provides a powerful, albeit invasive, means to study cellular processes in vivo at the very early stage of the disease process and at the very late stage of therapeutic intervention when the tumor burden is too small to be detected by other imaging methods.

Abstract 4035 INTRODUCTION: The interaction of multiple myeloma (MM) cells with the bone marrow (BM) microenvironment plays a crucial role in MM pathogenesis, implying that progression of MM occurs through continuous interaction between the BM and MM cells, which controls the ability of MM cells to egress out of the BM and home into new BM niches. We have previously shown that the CXCR4/SDF1 axis as well as Rho GTPases downstream of the receptor was important for chemotaxis, adhesion, homing and egress of MM cells. However, the driving force for MM cells to leave the BM and metastasize to other BM sites is not well understood. Regions of severe oxygen deprivation (hypoxia) arise in tumors due to rapid cell division and are associated with poor patient prognosis, cell motility, associated angiogenesis and metastasis. In this study, we tested the role of hypoxia in the dissemination of MM cells in vivo, as well as regulation of the retention/egress of MM cells in and out of the BM. METHODS: To test the effect of hypoxia on induction of MM egress, MM1s-GFP+/Luc+ cells were injected into 12 SCID mice, and then mice with different stages of tumor development (based on the tumor size detected by bioluminescence) were treated with the hypoxia marker pimonidazole. Blood was drawn and BM was obtained from the femur. Mononuclear cells were then fixed, permeabilized, and stained with antibodies against pimonidazole, followed with an APC- secondary antibody, PE-mouse-anti-human CXCR4, and anti-cadherin antibody followed by an Alexa-Fluor-594 secondary antibody. MM cells in BM and peripheral blood were identified by gating on cells with high GFP signal. To confirm the effects of severe hypoxia found in vivo compared to physiologic mild hypoxia found in the BM, we tested the effect of mild hypoxic conditions (6% O2) and severe hypoxic conditions (0.5% O2) on MM expression of cadherins and CXCR4, as well on functional adhesion of MM cells to stromal cells and chemotaxis. RESULTS: Twelve mice with different stages of MM tumor progression were used. A bi-phasic correlation between tumor progression and the percent of hypoxic cells in BM was found, showing that severe hypoxic conditions in the BM correlated with tumor burden. The correlation between the tumor burden and the number of circulating cells was not linear; however, a direct linear correlation was observed between the number of circulating MM cells and hypoxia in the BM. Moreover, hypoxia in BM correlated directly with the expression of CXCR4 and negatively correlated with the expression of cadherins in MM cells isolated from the BM. To test the effect of the severe hypoxic conditions induced by tumor progression compared to mild hypoxic conditions found physiologically in the BM, we tested the effect of 0.5% O2 (severe hypoxia) and 6% O2 (mild hypoxia) compared to normoxia (21%) on MM cell adhesion to BMSCs, as well as on chemotaxis in response to SDF1, as well as expression of CXCR4 and cadherins. We found that severe hypoxic conditions decreased MM expression of cadherins and adhesion to BMSCs, as well as increased expression of CXCR4 and chemotaxis to SDF1 compared to cells in normoxia. In contrast, mild hypoxic conditions did not alter the expression of CXCR4 and cadherins, adhesion of MM cells to BMSCs, or chemotaxis of MM to SDF1 compared to normoxic cells. CONCLUSION: Hypoxia in the BM directly correlates with the number of circulating MM cells, and with changes in expression of cadherins and CXCR4 in vivo. Severe hypoxic conditions, but not mild hypoxic conditions, induce hypoxic responses in MM cells. Based on these findings, further studies to manipulate hypoxia in order to regulate tumor dissemination as a therapeutic strategy in MM are warranted. Disclosures: Anderson: Millennium Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Ghobrial:Celgene: Membership on an entity's Board of Directors or advisory committees; Millennium: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees.

e14640 Background: MicroRNAs (miRNAs) are non-coding RNAs that act as negative regulators of gene expression. They have been described to play roles in solid tumors and hematologic malignancies. However the role of miRNAs in multiple myeloma (MM) has not been yet fully described. Methods: We performed miRNA-profiling of primary bone marrow-derived CD138+ MM cells, compared to their normal cellular counterparts and validated data by qRT-PCR. In vitro and in vivo functional studies were performed on miRNA-15a- and -16–1-precursors-transfected MM cells. Effect of miRNA-15a and -16–1 on signaling cascades have been evaluated by western blot and immunofluorescence. NF-kB activity has been studied using the Active Motif TransAM kit. In vivo MM cell growth has been evaluated by either using an in vivo imaging model or bioluminescence. Angiogenesis has been studied both in vitro and in vivo using the chorioallantoic membrane model. Results: We identified a MM-specific miRNA signature characterized by down-expression of miRNA-15a, -16–1 and over-expression of miRNA-222/-221/-382/-181a/-181b (P No significant financial relationships to disclose.

Then focused on the RTK’s which were shown to be upregulated in WM and tested the effect of TKI-258 effect on their activity. Moreover, we tested the effect of TKI-258 survival, proliferation, and apoptosis of WM cells, and its effect of different signaling pathways in WM. Results: We found that epidermal growth factor receptor (EGF-R), ephrin receptor (Eph-R) and receptor tyrosine kinase–like orphan receptor 1 (ROR-1) were highly activated in WM patients compared to normal subjects (5, 10, and 14-fold increase, respectively), and were found to be upregulated also in BCWM1. TKI-258 reduced the activity of EGF-R and Eph-R, but not ROR1. Moreover, TKI-258 induced cytotoxicity, prevented proliferation and induced apoptosis in WM cells in a dose dependent manner with IC50 of 500-800 nM. Moreover, it was shown to induce cleavage of PARP, caspase-3 and caspase-9, and also reduced phosphorylations of ERK1/2. Conclusion: We identified two novel therapeutic targets for WM; EGF-R and Eph-R, and identified Eph-R as a novel target of TKI-258. Moreover, TKI-258 reduced WM progression in vitro, and we are now testing the effect of TKI-258 on WM progression in vitro and alone and in combination with other drugs.

A survey of the participants identified a broad list of user interface issues, which were then grouped in the following categories: Information Exchange Realtime Intelligent Interfaces Support for Problem Solving

In conventional design practice, a detailed product description is the end-result of a design process. Usually these detailed product descriptions do not contain information linking their heritage from early-stage abstract product descriptions or the particular influence of different life-cycle perspectives. This “missing” information, a description of the multi-staged and multi-perspective design process, is termed a design evolution, and is a representation of the design rationale for a product description. This research focuses on the development of a methodology for Design Evolution Management, i.e. techniques for representation and subsequent utilization of a design evolution during a design process. Within this methodology, a design evolution is represented both at strategic and tactical levels. A prototype computer-based design environment called AIDEMS, based on this design methodology, has been built and is being tested in several design domains. This design environment provides design engineers a platform for expressing their design strategies and tactics and uses Artificial Intelligence programming techniques enabling semi-automated design assistance for: resource scheduling, explanation of design assertions, execution of design revisions, design inconsistency detection, and exploration of design alternatives.

The value of high polyunsaturated fatty acid (PUFA) diets in preventing diabetic nephropathy in rats was studied. Diabetes was induced by intravenous injection of streptozotocin (SZ), 65 mg/kg. Rats were divided in four groups fed diets containing 11 % fat for 38 weeks. Dietary fat derived from four sources: beef tallow (BT; rich in saturated fatty acids), evening primrose oil (EPO; rich in gammalinolenic [GLA] and linoleic acids [LA]), safflower oil (SO; rich in LA), and fish oil (F0; rich in eicosapentaenoic [EPA] and docosahexaenoic [DHA] acids). Ultralente insulin was administered every other day to maintain the blood glucose levels between 11.1 and 22.2 mmol/L (200 and 400 mg/dL). The diets prepared with EPO and SO had a clear beneficial effect on proteinuria, glomerular sclerosis, and tubular abnormalities, as compared with BT. Both diets also increased the ratio of renal cortical production of 6-keto-PGF,a to thromboxane B 2 (TXB 2 ), the stable metabolites of PGI 2 and TXA 2 , respectively. They did not induce significant changes in plasma lipid composition. The FO diet did not have an effect on renal disease, but decreased plasma lipids and inhibited eicosanoid synthesis by platelets and kidney cortex. FO feeding was associated with a lowered 6-keto-PGF 1α /TXB 2 ratio. It is concluded that high LA diets are protective in this model of diabetic nephropathy. The effect may be secondary to modifications of the eicosanoid balance. Diets containing FO have a beneficial effect on plasma lipids in this model.

The components of reading, W.A. Hoover and W.E. Tunmer a theory of knowledge sources and procedures for reading acquisition, G.B. Thompson and C.M. Fletcher-Finn the effects of type of instruction on processes of reading instruction, G.B. Thompson and R.S. Johnston the case against context, T. Nicholson reading without context, T. Nicholson language-related factors as sources of individual differences in the development of word recognition skills, W.E. Tunmer and W.A. Hoover appendix - reading instruction for the initial years in New Zealand schools, G.B. Thompson.

Three studies were conducted to examine individual differences among young children in the extent of use of alternative cognitive processes for word reading. The expectation was that boys, of the same reading attainment level as girls, tend to rely more than girls on access to phonological segments of words. In Study I a predicted pattern of gender differences was tested with 87 seven-year-old children reading pseudohomophones graphemicalty different and graphemically similar to lexically matched words. In Study II predicted differences were tested with the same children reading words of regular and exception grapheme-phoneme relationships. For 84 six-year-old children in Study III predicted differences were examined in the relationship of word reading accuracy to phonological consistency of initial segments of words. The results of the three studies supported the expectation.

This study examines the entry of young people into the full-time labour market. A model is presented in which young people are considered as decision makers in relation to both school and the labour market. School participation, in part, func tions as a short-term buffer for fluctuations in slackness of the labour market. The model satisfactorily describes data for New Zealand in the period 1966 to 1981. Implications are derived for the determination of 'hidden unemployment' among young people, and also for appraisal of duration of schooling as an indication of quality of labour force entrants.

Summary The evidence on sex differences in reading attainment of English‐speaking children is reviewed. There is found to be a developmental trend for sex differences in reading attainment, whereby a larger proportion of boys than girls make a slow beginning at learning to read, but by ten years of age population differences between boys and girls are no longer apparent. It is considered important that teachers and parents be aware that a boy under ten years who is making slow progress at learning to read may be an instance of this developmental phenomenon which does not imply any pathology such as dyslexia. Findings on sex differences in pre‐reading skills are examined and also hypotheses about the origin of sex differences in reading attainment. The hypotheses of feminine bias of the school environment, of differential maturation of cerebral structures, and of differential exposure to the printed word, are evaluated.

Summary. Data are presented to examine alternative interpretations of errors of different lexical status which occur as responses to word reading tests. In a sample of 261 6 1/2-year-old children, the incidence of non-lexical substitution errors was positively associated with level of reading progress, while that of lexical substitution errors was not. Beginner readers of high reading progress apparently made more attempts at phonological mediation and were more susceptible to breaking lexical constraints in their responses than children of low progress.

The nephrotic syndrome was induced in rats by intravenous adriamycin (3 mg/kg). The rats were then divided into four groups which, for six weeks, were pair-fed diets containing beef tallow (BT), fish oil (FO), a source of n-3 fatty acids, evening primrose oil (EPO), a source of n-6 fatty acids, or a combination of evening primrose oil and fish oil, 75:25 (EPO:FO). The fat content of the diets was 15%. Significant incorporation of the fatty acids into kidney phospholipids was demonstrated. Diets containing FO, EPO and EPO:FO lowered plasma triglycerides and total cholesterol levels as compared with diets containing BT. Only EPO:FO raised high density lipoprotein (HDL) cholesterol levels, as compared with BT. The combination EPO:FO prevented the tenfold suppression of aortic 6-keto-PGF1 alpha caused by FO. These changes in plasma lipids and eicosanoid production are potentially antiatherogenic and may prevent glomerular sclerosis. The combination of EPO and FO, containing n-6 and n-3 fatty acids may offer advantages over either family of fatty acids in this model of nephrotic syndrome.

Young children's understanding of the verbal terms 'easy' and 'hard' in describing personal competence at depicted activities was investigated with reference to a developmental sequence suggested by Heckhausen (1982) to describe the child's understanding of concepts concerning personal achievement. The consistency of children's judgments rather than their realism or accuracy was the criterion used for investigating each of two developmental levels of understanding. For the 3-and 4-year-old children in studies 1 and 2, there was consistency between responses to the terms 'can'/'can't' and the terms 'easy'/'hard'. At the higher developmental level, in study 3, both 5-and 7-year-olds were able to make consistent unidimensional orderings of the level of difficulty of activities.