Grade-Point Averages of Oversears Military-Dependent Students Compared to Grade-Point Averages of Non-Military Students

The major purpose of this investigation was to make a comparison of grade-point averages, earned by military dependent students in overseas Dependent Schools, with the grade-point averages of a comparably non-mobile student society with whom they graduated in the united states. The study of the situation existing in the Novato High School, Novato, Marin County, California over a period of years prompted the investigation conducted during the school year 1971-1972. Data for the investigation was derived from the permanent record cards of 2,173 graduated students over a period of five graduating classes, 1966- 1970. The Novato High School has been for many years, the terminus of high school education for military-dependent students whose parents are assigned to the Hamilton Air Force Base, which is located within the city limits of Novato, California. Procedure for the investigation was to identify those permanent records of military-dependent students who had studied in one Overseas Dependent School for at least one semester of their four years of high school work. Ninety-nine identified students were included in the investigation and designated: Group A (Military-Dependent) students. .;., The number of overseas military-dependent students identified represented less than ten percent of the class they graduated with. Employing a table of random numbers as the method for selection, 99 non-military and non-mobile students of the same graduating classes were chosen as the comparison group and designated: Group B (Non-Military) students. A total of 198 students were included in the study. The criterion variables used in this investigation were the following: 1) Class Year, 2) Sex, 3) Grade-Point Average, 4) Area of overseas Study; viz, Europe or Pacific 5) Number of Semesters Studied overseas. Variables 4 and 5 were for correlation studies within the military-dependent group, only. Statistical design for analysis of the data employed the use of the G4 CAL T Test for multiple analysis of variance procedure; two-tailed t tests were used to test the null hypotheses generated by the investigation. The analysis was made through employment of the computer at the University of California, Berkeley. As a result of questions proposed during the investigation five null hypotheses were tested for significance at the .05 level of confidence with the following results: 1. There is no significant difference in mean grade-point averages of Group A (Military-Dependents) and Group B (Non-Military) students. The null hypothesis was rejected. 2. There is no significant difference in mean grade point average achievement between military-dependent males and non-military males. The null hypothesis was rejected. 3. There is no significant difference in mean grade point average achievement between military-dependent females and :n,on-mili tary females. The null hypothesis was accepted. 4. There is no significant relationship within the military, between the area of study and any other variable particularly grade-point average. The null hypothesis was accepted. 5. There is no significant relationship within the military between semesters overseas and any other variable studied particularly grade-point average. The null hypothesis was accepted. As a result of this investigation it is recommended that similar studies be conducted in school districts that have a transient military-dependent student body from overseas. To validate the findings of this investigation it is suggested that additional variables, comparable to both groups, be added to measure achievement as proof that mobility affects achievement. Studies should be made to assure that the curriculum of secondary schools meets the needs of a society that is apparently more mobile than in any other time in the history of the United States. Investigations should also be made of mobile students whose parents are employed by national corporations owning subsidiary companies in foreign lands, and for whom movement with family to these foreign posts is necessary. Where these students obtain their education, and achievement recorded, is important to further comprehension of academic success of A

MenaINV dysregulates cortactin phosphorylation to promote invadopodium maturation

Invadopodia, actin-based protrusions of invasive carcinoma cells that focally activate extracellular matrix-degrading proteases, are essential for the migration and intravasation of tumor cells during dissemination from the primary tumor. We have previously shown that cortactin phosphorylation at tyrosine residues, in particular tyrosine 421, promotes actin polymerization at newly-forming invadopodia, promoting their maturation to matrix-degrading structures. However, the mechanism by which cells regulate the cortactin tyrosine phosphorylation-dephosphorylation cycle at invadopodia is unknown. Mena, an actin barbed-end capping protein antagonist, is expressed as various splice-isoforms. The MenaINV isoform is upregulated in migratory and invasive sub-populations of breast carcinoma cells, and is involved in tumor cell intravasation. Here we show that forced MenaINV expression increases invadopodium maturation to a far greater extent than equivalent expression of other Mena isoforms. MenaINV is recruited to invadopodium precursors just after their initial assembly at the plasma membrane, and promotes the phosphorylation of cortactin tyrosine 421 at invadopodia. In addition, we show that cortactin phosphorylation at tyrosine 421 is suppressed by the phosphatase PTP1B, and that PTP1B localization to the invadopodium is reduced by MenaINV expression. We conclude that MenaINV promotes invadopodium maturation by inhibiting normal dephosphorylation of cortactin at tyrosine 421 by the phosphatase PTP1B.United States. National Institutes of Health (CA150344)United States. National Institutes of Health (CA100324

Track Extrapolation and Distribution for the CDF-II Trigger System

The CDF-II experiment is a multipurpose detector designed to study a wide range of processes observed in the high energy proton-antiproton collisions produced by the Fermilab Tevatron. With event rates greater than 1MHz, the CDF-II trigger system is crucial for selecting interesting events for subsequent analysis. This document provides an overview of the Track Extrapolation System (XTRP), a component of the CDF-II trigger system. The XTRP is a fully digital system that is utilized in the track-based selection of high momentum lepton and heavy flavor signatures. The design of the XTRP system includes five different custom boards utilizing discrete and FPGA technology residing in a single VME crate. We describe the design, construction, commissioning and operation of this system.Comment: 34 pages, 9 figures, submitted to Nucl.Inst.Meth.

Guidance of sentinel lymph node biopsy decisions in patients with T1-T2 melanoma using gene expression profiling.

AIM: Can gene expression profiling be used to identify patients with T1-T2 melanoma at low risk for sentinel lymph node (SLN) positivity? PATIENTS & METHODS: Bioinformatics modeling determined a population in which a 31-gene expression profile test predicted \u3c5% SLN positivity. Multicenter, prospectively-tested (n = 1421) and retrospective (n = 690) cohorts were used for validation and outcomes, respectively. RESULTS: Patients 55-64 years and ≥65 years with a class 1A (low-risk) profile had SLN positivity rates of 4.9% and 1.6%. Class 2B (high-risk) patients had SLN positivity rates of 30.8% and 11.9%. Melanoma-specific survival was 99.3% for patients ≥55 years with class 1A, T1-T2 tumors and 55.0% for class 2B, SLN-positive, T1-T2 tumors. CONCLUSION: The 31-gene expression profile test identifies patients who could potentially avoid SLN biopsy

Cofilin is a pH sensor for actin free barbed end formation: role of phosphoinositide binding

Newly generated actin free barbed ends at the front of motile cells provide sites for actin filament assembly driving membrane protrusion. Growth factors induce a rapid biphasic increase in actin free barbed ends, and we found both phases absent in fibroblasts lacking H+ efflux by the Na-H exchanger NHE1. The first phase is restored by expression of mutant cofilin-H133A but not unphosphorylated cofilin-S3A. Constant pH molecular dynamics simulations and nuclear magnetic resonance (NMR) reveal pH-sensitive structural changes in the cofilin C-terminal filamentous actin binding site dependent on His133. However, cofilin-H133A retains pH-sensitive changes in NMR spectra and severing activity in vitro, which suggests that it has a more complex behavior in cells. Cofilin activity is inhibited by phosphoinositide binding, and we found that phosphoinositide binding is pH-dependent for wild-type cofilin, with decreased binding at a higher pH. In contrast, phosphoinositide binding by cofilin-H133A is attenuated and pH insensitive. These data suggest a molecular mechanism whereby cofilin acts as a pH sensor to mediate a pH-dependent actin filament dynamics

Cofilin determines the migration behavior and turning frequency of metastatic cancer cells

We have investigated the effects of inhibiting the expression of cofilin to understand its role in protrusion dynamics in metastatic tumor cells, in particular. We show that the suppression of cofilin expression in MTLn3 cells (an apolar randomly moving amoeboid metastatic tumor cell) caused them to extend protrusions from only one pole, elongate, and move rectilinearly. This remarkable transformation was correlated with slower extension of fewer, more stable lamellipodia leading to a reduced turning frequency. Hence, the loss of cofilin caused an amoeboid tumor cell to assume a mesenchymal-type mode of movement. These phenotypes were correlated with the loss of uniform chemotactic sensitivity of the cell surface to EGF stimulation, demonstrating that to chemotax efficiently, a cell must be able to respond to chemotactic stimulation at any region on its surface. The changes in cell shape, directional migration, and turning frequency were related to the re-localization of Arp2/3 complex to one pole of the cell upon suppression of cofilin expression

MARCKS phosphorylation is modulated by a peptide mimetic of MARCKS effector domain leading to increased radiation sensitivity in lung cancer cell lines

Lung cancer is the leading cause of cancer-associated mortality in the United States. Kinase hyperactivation is a known mechanism of tumorigenesis. The phosphorylation status of the plasma membrane-associated protein myristoylated alanine rich C-kinase substrate (MARCKS) effector domain (ED) was previously established as being important in the sensitivity of lung cancer to radiation. Specifically, when MARCKS ED was in a non-phosphorylated state, lung cancer cells were more susceptible to ionizing radiation and experienced prolonged double-strand DNA breaks. Additional studies demonstrated that the phosphorylation status of MARCKS ED is important for gene expression and in vivo tumor growth. The present study used a peptide mimetic of MARCKS ED as a therapeutic intervention to modulate MARCKS phosphorylation. Culturing A549, H1792 and H1975 lung cancer cell lines with the MARCKS ED peptide led to reduced levels of phosphorylated MARCKS and phosphorylated Akt serine/threonine kinase 1. Further investigation demonstrated that the peptide therapy was able to reduce lung cancer cell proliferation and increase radiation sensitivity. In addition, the MARCKS peptide therapy was able to prolong double-strand DNA breaks following ionizing radiation exposure. The results of the present study demonstrate that a peptide mimetic of MARCKS ED is able to modulate MARCKS phosphorylation, leading to an increase in sensitivity to radiation. Keywords: lung cancer, myristoylated alanine rich C-kinase substrate, radiation sensitivity, effector domain, peptide mimeti

Rfam: updates to the RNA families database

Rfam is a collection of RNA sequence families, represented by multiple sequence alignments and covariance models (CMs). The primary aim of Rfam is to annotate new members of known RNA families on nucleotide sequences, particularly complete genomes, using sensitive BLAST filters in combination with CMs. A minority of families with a very broad taxonomic range (e.g. tRNA and rRNA) provide the majority of the sequence annotations, whilst the majority of Rfam families (e.g. snoRNAs and miRNAs) have a limited taxonomic range and provide a limited number of annotations. Recent improvements to the website, methodologies and data used by Rfam are discussed. Rfam is freely available on the Web at http://rfam.sanger.ac.uk/and http://rfam.janelia.org/

EGF-induced PIP2 hydrolysis releases and activates cofilin locally in carcinoma cells

Lamellipodial protrusion and directional migration of carcinoma cells towards chemoattractants, such as epidermal growth factor (EGF), depend upon the spatial and temporal regulation of actin cytoskeleton by actin-binding proteins (ABPs). It is generally hypothesized that the activity of many ABPs are temporally and spatially regulated by PIP2; however, this is mainly based on in vitro–binding and structural studies, and generally in vivo evidence is lacking. Here, we provide the first in vivo data that directly visualize the spatial and temporal regulation of cofilin by PIP2 in living cells. We show that EGF induces a rapid loss of PIP2 through PLC activity, resulting in a release and activation of a membrane-bound pool of cofilin. Upon release, we find that cofilin binds to and severs F-actin, which is coincident with actin polymerization and lamellipod formation. Moreover, our data provide evidence for how PLC is involved in the formation of protrusions in breast carcinoma cells during chemotaxis and metastasis towards EGF