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This paper evaluates the hypothesis that globalization has increased the role of international factors and decreased the role of domestic factors in the inflation process in industrial economies. Towards that end, we estimate standard Phillips curve inflation equations for 11 industrial countries and use these estimates to test several predictions of the globalization and inflation hypothesis. Our results provide little support for this hypothesis. First, the estimated effect of foreign output gaps on domestic consumer price inflation is generally insignificant and often of the wrong sign. Second, we find no evidence that the trend decline in the sensitivity of inflation to the domestic output gap observed in many countries owes to globalization. Finally, and most surprisingly, our econometric results indicate no increase over time in the responsiveness of inflation to import prices for most countries.

Using a genome-wide technical knockout, we isolated a newly identified set of GRIM (genes associated with retinoid-interferon-induced mortality) genes; GRIM genes mediate IFN- and retinoic-acid (RA)-induced cell death. Here, we describe the isolation and characterization of one such gene, GRIM-1. Three proteins, with identical C-termini, were produced from the GRIM-1 open reading frame when this gene was transcribed and translated in vitro. These protein isoforms, designated GRIM-1α, GRIM-1β and GRIM-1γ, differentially suppressed growth via apoptosis in various cell lines. We also show that a caspase-dependent mechanism generates the proapoptotic GRIM-1 isoforms. Lastly, GRIM-1 isoforms differentially blocked maturation of 18S ribosomal RNA, consistent with their respective growth-suppressive ability. Together, these studies identified a novel protein involved in growth suppression and cell death.

Drug resistance is a major obstacle in cancer treatments and diminishes the clinical efficacy of biological, cytotoxic, or targeted therapeutics. Being an antiapoptotic mediator of chemoresistance in breast and lung cancer cells, MKP1 phosphatase might be targeted for overcoming chemoresistance and improving therapeutic efficacy. In this work, tyrosine phosphatase inhibitor-3 (TPI-3) was identified as a novel small molecule inhibitor of MKP1 and was capable of sensitizing tumors to bio- and chemotherapeutics in mice as a tolerated oral agent. Effective against recombinant MKP1, TPI-3 selectively increased MKP1 phosphosubstrates in Jurkat cells and induced cell death via apoptosis at nanomolar concentrations. TPI-3 also increased MKP1 phosphosubstrates in WM9 human melanoma cells and synergized with biotherapeutic IFNα2b in the growth inhibition of melanoma cells in vitro (combination index

In this paper, two types of multiple binary zero correlation zone (ZCZ) sequence sets are constructed: 1. Each set is a binary (2n+1Zcz,2n, Zcz)-ZCZ sequence set, which is one of the best cases in the known constructions. 2. Among all the sets, the sequences still possess good cross-correlation property within the zone of length Z ≤ Zcz. In particular, the first type sequence sets have a common zero correlation zone of length Z, which solves the previous research problem. These multiple binary ZCZ sequence sets are suitable for multiuser environments.

We have previously isolated GRIM-19, a novel growth suppressor, using a genetic method. GRIM-19 ablates cell growth by inhibiting the transcription factor signal transducer and activator of transcription 3 (STAT3). Up-regulation of STAT3 and growth promotion were observed in a number of human tumors. Although the tumor-suppressive actions of GRIM-19 are known, the structural elements required for its antitumor actions are not understood. Mutational and protein sequence analyses identified a motif in the N terminus of GRIM-19 that exhibited similarity to certain RNA viral proteins. We show that disruption of specific amino acids within this motif cripples the antitumor actions of GRIM-19. These mutants fail to interact with STAT3 efficiently and consequently do not inhibit growth-promoting gene expression. More importantly, we show that a clinically observed mutation in the N terminus of GRIM-19 also weakened its interaction with STAT3 and antitumor action. Together, these studies identify a major role for the N terminus of GRIM-19 in mediating its tumor-suppressive actions.

12020Background: Despite remarkable upfront response to ALK tyrosine kinase inhibitors (TKIs) in ALK+ lung cancer, acquired resistance eventually develops. Molecular mechanisms of the initial emerg...

470Background: Trimodality therapy with TURBT followed by concurrent chemoradiation is an alternative to cystectomy in selected patients with muscle invasive BCa. Identifying genetic determinants o...

Objectives To evaluate the presence of moral hazard, adjusted for the propensity to have self-purchased insurance policies, employer-based medical benefits, and welfare-associated medical benefits in Hong Kong. Methods Based on 2005 population survey, we used logistic regression and zero-truncated negative binomial/Poisson regressions to assess the presence of moral hazard by comparing inpatient and outpatient utilization between insured and uninsured individuals. We fitted each enabling factor specific to the type of service covered, and adjusted for predisposing socioeconomic and demographic factors. We used a propensity score approach to account for potential adverse selection. Results Employment-based benefits coverage was associated with increased access and intensity of use for both inpatient and outpatient care, except for public hospital use. Similarly, welfare-based coverage had comparable effect sizes as employment-based schemes, except for the total number of public ambulatory episodes. Self-purchased insurance facilitated access but did not apparently induce greater demand of services among ever users. Nevertheless, there was no evidence of moral hazard in public hospital use. Conclusions Our findings suggest that employment-based benefits coverage lead to the greatest degree of moral hazard in Hong Kong. Future studies should focus on confirming these observational findings using a randomized design.

Introduction Les pontages femoropoplites (PFP) sont frequemment realises. Une proportion significative de pontages s'occlut dans la premiere annee en raison de lesions d'hyperplasie intimale (HI). Methodes La partie clinique de cette etude a concerne 43 patients ayant beneficie d'un PFP qui s'est occlus dans la premiere annee apres sa realisation et traite avec succes par une thrombolyse. Les changements morphologiques de l'intima au niveau des anastomoses (evaluation angiographique) et l'angle de l'anastomose distale latero-terminale ont ete analyses. Dans la seconde partie de l'etude, le flux sanguin dans l'anastomose a ete modelise experimentalement (par velocimetrie par images de particules) et numeriquement (par modelisation numerique de la dynamique des fluides). Les resultats ont ete correles avec la localisation des lesions d'HI identifiees precedemment. Resultats Nous avons constate que la localisation des lesions d'HI etait correlee avec la localisation des flux turbulents, avec l'accroissement des contraintes de cisaillement, et avec les points de stagnation. Nous avons egalement pu confirmer que les anastomoses a angle aigu etaient moins susceptibles de presenter des lesions d'HI et d'induire une occlusion du pontage. Conclusion Nos resultats suggerent qu'une meilleure comprehension des caracteristiques hemodynamiques et de leur influence sur l'HI devraient aider a la creation d'un design optimise du materiel servant au pontage, avec en particulier un angle anastomotique plus aigu.

Antecedentes La derivacion femoropoplitea es un procedimiento reconstructivo vascular frecuente. Al cabo de un ano, una proporcion significativa de los injertos de derivacion dejan de ser funcionales debido a la oclusion por progresion de la hiperplasia intimal (HI). Metodos La parte clinica del estudio ha consistido en el analisis de 43 pacientes tratados con una derivacion femoropoplitea supragenicular ocluida al ano del procedimiento, tratados satisfactoriamente mediante trombolisis. Se evaluaron angiograficamente los cambios morfologicos de la intima en la anastomosis y el angulo de la anastomosis terminolateral distal. En la segunda parte del estudio, se realizo un modelo experimental (mediante velocimetria por imagen de particulas) del flujo sanguineo en la anastomosis terminolateral distal y numericamente (mediante dinamica de fluidos computacional). Los resultados se correlacionaron con las localizaciones de HI identificadas previamente. Resultados Demostramos que la localizacion de los focos de HI se correlacionan con los de alteracion del flujo sanguineo, de aumento de la tension de cizallamiento de la pared, y con los puntos de estancamiento, segun lo documentado por los hallazgos de la visualizacion experimental y los angiograficos. Tambien confirmamos que las anastomosis con angulos mas agudos son menos propensas a HI y a la oclusion de la luz. Conclusion Sugerimos que una mejor comprension de la hemodinamica y de su influencia en la HI deberia dar lugar a un diseno optimizado de los injertos, mediante la adopcion de un angulo mas agudo en las anastomosis.

There is an increasing evidence that long-term alcohol intake can promote damage to most of the body's major organs. However, regular consumption of a small-moderate amount of alcohol is often recommended as being beneficial to health and of concern is that the effect of ingesting commercially available alcohol products on steroid hormone synthesis under variable nutritional conditions has not been thoroughly investigated. Many individuals consume alcohol alone prior to a meal and the aim of the present study was to assess the effect of consuming a small-moderate amount of commercially available alcohol on the level of salivary cortisol and salivary dehydroepiandrosterone sulfate (DHEAS) before and after a meal. A total of 24 males aged 19–22 years participated in the current investigation. The experimental procedure required participants to fast for 6 h before being asked to ingest either 40 g alcohol in the form of red wine ( n = 8), low alcohol and high beer ( n = 8), white wine ( n = 8) or the equivalent amount of placebo over a 135-min period before consuming food for 45-min. The level of blood alcohol, salivary cortisol and salivary DHEAS was assessed upon arrival and then at regular 45-min intervals during the 180-min experimental period. The results showed that the consumption of alcohol and placebo can significantly lower the level of salivary cortisol. However, the effect of consuming a small-moderate amount of commercially available alcohol on the level of salivary DHEAS was dependent on the nutritional content of the beverage with red wine promoting no change, white wine promoting a significant decrease, and beer having a variable effect on salivary DHEAS concentration when compared to placebo. It was concluded that the effect of commercially available alcohol on the HPA axis is not the same for all alcohol products and both the nutritional status of participants and the nutritional content of the alcoholic beverage being administered should be taken into consideration when investigating the effect of alcohol on the HPA axis.

Zusammenfassung Bei experimenteller Tetrachlorkohlenstoff- und Thioacetamid-Cirrhose der Ratte wurden die mannlichen Gonaden histologisch und autoradiographisch nach in vivo-Inkorporation von 3H-Thymidin untersucht. Die deutliche Verminderung der 3H-Thymidin-Inkorporation in die Spermatogonien ist ein Hinweis fur die Hemmung der DNS-Synthese und damit fur die Senkung der spermatogenetischen Aktivitat der Hodentubuli bei experimenteller Lebercirrhose. Bei ausschlieslich histologischer Beobachtung des Hodens sind diese Veranderungen nicht so evident wie bei der autoradiographischen Untersuchung. Die Atrophie der Samenblaschen und der Prostata weist auf eine Verminderung der endokrinen Funktion des Hodens bei beiden Cirrhoseformen hin. Als pathogenetischer Mechanismus ist eine direkte Schadigung des Hodens durch das verabreichte Gift zumindest bei der Tetrachlorkohlenstoff-Cirrhose moglich. Auserdem stellt die Verschlechterung des Ernahrungs- und Stoffwechselzustandes der Tiere beider Cirrhose-Gruppen eine wesentliche Ursache der primaren Hodenschadigung dar. Es wird angenommen, das es sich nicht um die Folgen eines Gonadotropin-Mangels handelt, da der Hypophysenvorderlappen ausreichend gonadotrope Zellen enthalt. Die Hodenveranderungen bei experimenteller Cirrhose werden also als primarer Hodenschaden gedeutet, eine mangelnde Bereitstellung von gebildetem Gonadotropin kann allerdings nicht ausgeschlossen werden. Die Reaktionsfahigkeit der Hoden auf eine hochdosierte exogene Gonadotropin-Zufuhr ist bei beiden Typen einer chronischen experimentellen Lebervergiftung bei der Ratte herabgesetzt. Eine zusatzliche Prednisolon-Behandlung hat bei beiden Lebercirrhose-Formen keinen gunstigen Einflus auf die beschriebene Hodenschadigung der Ratte.

GRIM-19 (Gene associated with Retinoid-Interferon-induced Mortality 19) is a novel tumor suppressor regulated by interferon/retinoid combination. We have recently shown that GRIM-19 inhibits v-Src-induced oncogenic transformation and metastatic behavior of cells. Oncogenic v-Src induces cell motility by cytoskeletal remodeling, especially the formation of podosomes and. Here, we show that GRIM-19 inhibited the v-Src-induced cell motility by inhibiting cytoskeletal remodeling, that is, podosome formation. We also show that the N terminus of GRIM-19 played a major role in this process and identified critical residues in this region. More importantly, we show that tumor-associated GRIM-19 mutations disrupted its ability to inhibit v-Src-induced cell motility. These actions appear to occur independently of STAT3, a known target of GRIM-19-mediated inhibition. Lastly, tumor-associated GRIM-19 mutants significantly lost their ability to control v-Src-induced metastases in vivo, indicating the biological and pathological significance of these observations.

Testicular temperature highly correlates with scrotal temperature. It has been postulated that cycling is associated with increased scrotal temperatures with time and consecutively with impaired semen quality. The aim of this study was to evaluate the influence of moderate cycling on scrotal temperature during highly standardized conditions in an experimental lab. A total of 25 volunteers without a history of infertility and normal andrological examination were included for scrotal temperature evaluation. Scrotal temperatures were measured every minute with a portable data recorder connected with two thermistor temperature sensors, which were attached on either side of the scrotum. A further thermistor sensor was attached on the central surface of the bicycle saddle. Ambient temperature in the study room was adjusted to 22 degrees C throughout the whole experiment. All volunteers started the experiment at the same daytime. Clothing of the volunteers consisted of standardized cotton wool trousers and shirts fitting to body size. After acclimatization to the study room in a sitting posture, each volunteer cycled on an exercise cycle for 60 min with a power of 25 Watt representing a speed of 25.45 km/h respectively. The saddle surface temperature reached in the median 35.59 degrees C after 60 min cycling. Median values of scrotal temperatures increased from 35.75 degrees C at the beginning to 35.82 degrees C after 60 min for the left side and from 35.50 to 35.59 degrees C for the right side. No correlation between cycling duration and scrotal temperatures could be found using multivariate anova for repeated measurements. However, scrotal temperatures during cycling were significantly lower (p < 0.001) compared with the last 10 min in sitting posture before starting cycling with a difference of 1.31 degrees C for the left and 1.46 degrees C for the right side. The present study suggests that moderate cycling under standardized conditions with a power of 25 Watt is not a major genital heat stress factor.

Metal-organic chemical vapour deposition (MOCVD) of various phases in PrO x system has been studied in relation with deposition temperature (450–750 °C) and oxygen partial pressure (0.027–100 Pa or 0.2–750 mTorr). Depositions were carried out by pulsed liquid injection MOCVD using Pr(thd) 3 (thd = 2,2,6,6-tetramethyl-3,5-heptanedionate) precursor dissolved in toluene or monoglyme. By varying deposition temperature and oxygen partial pressure amorphous films or various crystalline PrO x phases (Pr 2 O 3 , Pr 7 O 12 , Pr 6 O 11 ) and their mixtures can be grown. The pure crystalline Pr 2 O 3 phase grows only in a narrow range of partial oxygen pressure and temperature, while high oxygen pressure (40–100 Pa) always leads to the most stable Pr 6 O 11 phase. The influence of annealing under vacuum at 750 °C on film phase composition was also studied. Near 90% step coverage conformity was achieved for PrO x films on structured silicon substrates with aspect ratio 1:10. In air degradation of Pr 2 O 3 films with transformation to Pr(OH) 3 was observed in contrast to Pr 6 O 11 films.

Interferons (IFNs) inhibit the growth of infectious pathogens and tumor development. Although IFNs are potent tumor suppressors, they modestly inhibit the growth of some human solid tumors. Their weak activity against such tumors is augmented by co-treatment with differentiation-inducing agents such as retinoids. Previous studies from our laboratory identified a novel gene product, gene associated with retinoid-interferon-induced mortality (GRIM)-19, as an IFN/all-trans retinoic acid-induced growth suppressor. However, the mechanisms of its growth suppressive actions are unclear. The src-family of tyrosine kinases is important regulators of various cell growth responses. Mutational activation of src causes cellular transformation by altering transcription and cytoskeletal properties. In this study, we show that GRIM-19 suppresses src-induced cellular transformation in vitro and in vivo by down-regulating the expression of a number of signal transducer and activator of transcription-3 (STAT3)-dependent cellular genes. In addition, GRIM-19 inhibited the src-induced cell motility and metastasis by suppressing the tyrosyl phosphorylation of focal adhesion kinase, paxillin, E-cadherin, and gamma-catenin. Effects of GRIM-19 on src-induced cellular transformation are reversible in the presence of specific short hairpin RNA, indicating its direct effect on transformation. GRIM-19-mediated inhibition of the src-induced tyrosyl phosphorylation of cellular proteins, such as focal adhesion kinase and paxillin, seems to occur independently of the STAT3 protein. GRIM-19 had no significant effect on the cellular transformation induced by other oncogenes such as myc and Ha-ras. Thus, GRIM-19 not only blocks src-induced gene expression through STAT3 but also the activation of cell adhesion molecules.

BACKGROUND Metastasis is a process by which tumors spread from primary organs to other sites in the body and is the major cause of death for cancer patients. The ovarian cancer G protein-coupled receptor 1 (OGR1) gene has been shown to be expressed at lower levels in metastatic compared with primary prostate cancer tissues. METHODS We used an orthotopic mouse metastasis model, in which we injected PC3 metastatic human prostate cancer cells stably transfected with empty vector (vector-PC3) or OGR1-expressing vector (OGR1-PC3) into the prostate lobes of athymic or NOD/SCID mice (n = 3-8 mice per group). Migration of PC3 cells transiently transfected with vector control or with OGR1- or GPR4 (a G protein-coupled receptor with the highest homology to OGR1)-expressing vectors was measured in vitro by Boyden chamber assays. G protein alpha-inhibitory subunit 1 (G alpha(i1)) expression after treatment with pertussis toxin (PTX) was measured using immunoblotting analysis. The inhibitory factor present in the conditioned medium was extracted using organic solvents and analyzed by mass spectrometry. RESULTS In vivo, all 26 mice carrying tumors that were derived from vector-PC3 cells developed prostate cancer metastases (mean = 100%, 95% confidence interval [CI] = 83.97% to 100%) but few (4 of 32) mice carrying tumors derived from OGR1-expressing PC3 cells (mean = 12.50%, 95% CI = 4.08% to 29.93%) developed metastases. However, exogenous OGR1 overexpression had no effect on primary prostate tumor growth in vivo. In vitro, expression of OGR1, but not GPR4, inhibited cell migration (mean percentage of cells migrated, 30.2% versus 100%, difference = 69.8%, 95% CI = 63.0% to 75.9%; P

We previously showed that inositol hexakisphosphate kinase 2 (IHPK2) functions as a growth-suppressive and apoptosis-enhancing kinase during cell stress. Overexpression of IHPK2 sensitized ovarian carcinoma cell lines to the growth-suppressive and apoptotic effects of interferon beta (IFN-beta), IFN-alpha2, and gamma-irradiation. Expression of a kinase-dead mutant abrogated 50% of the apoptosis induced by IFN-beta. Because the kinase-dead mutant retained significant response to cell stressors, we hypothesized that a portion of the death-promoting function of IHPK2 was independent of its kinase activity. We now demonstrate that IHPK2 binds to tumor necrosis factor (TNF) receptor-associated factor (TRAF) 2 and interferes with phosphorylation of transforming growth factor beta-activated kinase 1 (TAK1), thereby inhibiting NF-kappaB signaling. IHPK2 contains two sites required for TRAF2 binding, Ser-347 and Ser-359. Compared with wild type IHPK2-transfected cells, cells expressing S347A and S359A mutations displayed 3.5-fold greater TAK1 activation following TNF-alpha. This mutant demonstrated a 6-10-fold increase in NF-kappaB DNA binding following TNF-alpha compared with wild type IHPK2-expressing cells in which NF-kappaB DNA binding was inhibited. Cells transfected with wild type IHPK2 or IHPK2 mutants that lacked S347A and S359A mutations displayed enhanced terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling staining following TNF-alpha. We believe that IHPK2-TRAF2 binding leads to attenuation of TAK1- and NF-kappaB-mediated signaling and is partially responsible for the apoptotic activity of IHPK2.

Posttraumatische Pseudozysten sind seltene Begleiterscheinungen von Thoraxtraumata bei Personen

We consider the design of a block equalizer for an intersymbol interference channel, given that the channel impulse response is not perfectly known at the receiver. In contrast to other schemes, our receiver is designed for imperfect channel state information and incorporates the statistics of the channel estimation error. In particular, we suggest an error model for data transmission that takes the influence from the data symbols on the estimation noise into account. We derive the optimum detection rule for the considered error model according to the maximum likelihood criterion and verify that the covariance matrix of the estimation noise depends on the actual transmitted data symbols. Motivated by this result, we propose a realizable receiver structure adopting the turbo principle that exploits the data-dependency of the covariance matrix of the estimation noise. The proposed scheme outperforms conventional receivers that neglect the exact statistics of the estimation noise. The core of our receiver is a soft-input soft-output block equalizer based on constrained minimum variance filter design. We assess the performance of the proposed turbo equalization scheme for block Rayleigh fading channels, applying both one-shot training-based channel estimation and iterative data-aided channel estimation

The removal of carbon dioxide (CO2) from industrial emissions has become essential in the fight against climate change. In this study, we employed Zeolite 13X for the capture and recovery of CO2 in a flow through system where the adsorbent was subjected to five adsorption-desorption cycles. The influent stream contained 1.5% CO2 at standard conditions. The adsorbent bed was 1 in. in length and 1 in. 3/8 in dia., and was packed with 10 g of the zeolite. Temperature swing adsorption (TSA) was employed as the regeneration method through heating to approximately 135 °C with helium as the purge gas. The adsorbent capacity at 90% saturation was found to decrease from 78 to 60gCO2/kgZeolite13X after the fifth cycle. The CO2 capture ratio or the mass of CO2 adsorbed to the total mass that entered the system decreased from 63% to only 61% after the fifth cycle. The CO2 recovery efficiency ranged from 82 to 93% during desorption, and the CO2 relative recovery, i.e., CO2 desorbed for the nth cycle to CO2 adsorbed for the first cycle, ranged from 88 to 68%. The service life of the adsorbent was determined to be equal to eleven cycles at a useful capacity of 40gCO2/kgZeolite13X. © 2007 American Institute of Chemical Engineers AIChE J, 2007

Background— Ultrasound can increase tissue blood flow, in part, through the intravascular shear produced by oscillatory pressure fluctuations. We hypothesized that ultrasound-mediated increases in perfusion can be augmented by microbubble contrast agents that undergo ultrasound-mediated cavitation and sought to characterize the biological mediators. Methods and Results— Contrast ultrasound perfusion imaging of hindlimb skeletal muscle and femoral artery diameter measurement were performed in nonischemic mice after unilateral 10-minute exposure to intermittent ultrasound alone (mechanical index, 0.6 or 1.3) or ultrasound with lipid microbubbles (2×10 8 IV). Studies were also performed after inhibiting shear- or pressure-dependent vasodilator pathways, and in mice with hindlimb ischemia. Ultrasound alone produced a 2-fold increase ( P P P 2a receptors and epoxyeicosatrienoic acids had minimal effect. Limb nitric oxide production and muscle phospho-endothelial nitric oxide synthase increased in a stepwise fashion by ultrasound and ultrasound with microbubbles. In mice with unilateral hindlimb ischemia (40%–50% reduction in flow), ultrasound (mechanical index, 1.3) with microbubbles increased perfusion by 2-fold to a degree that was greater than the control nonischemic limb. Conclusions— Increases in muscle blood flow during high-power ultrasound are markedly amplified by the intravascular presence of microbubbles and can reverse tissue ischemia. These effects are most likely mediated by cavitation-related increases in shear and activation of endothelial nitric oxide synthase.

Preclinical studies had determined that tamoxifen and interferon-alpha2b (IFN-alpha2b) synergistically inhibited growth of both estrogen-receptor positive and negative murine tumor xenografts and had combined antiangiogenic effects and that tamoxifen potentiated IFN-stimulated gene (ISG) expression. A phase I trial in 26 patients was conducted using the combination to define tolerance and potentiation of ISG expression. IFN- alpha2b at a dose of 3 x 10(6) units/m(2) daily was given subcutaneously (s.c.), and tamoxifen was initiated as a loading dose of 150 mg/m(2) and then 60 mg/m(2) twice daily on day 8. At this initial dose, reduction of dose of IFN- alpha2b was required in 4 of 11 patients, primarily because of fatigue. Another group of patients was treated with an identical tamoxifen dose but with IFN-alpha2b reduced to 2 x 10(6)/m(2) U; this was better tolerated. As the projected serum tamoxifen level to reduplicate preclinical effects was 300 mg/m(2), dose escalation in a third cohort was undertaken; it had to be discontinued secondary to grade III or IV toxicity in 2 of 2 patients. Increases in products of transcriptionally regulated ISGs, beta (2)-microglobulin, neopterin, and ISG15 were assessed. All ISGs increased after IFN-alpha2b, but only ISG15 had a further significant rise after initiation of tamoxifen. Because at doses not limited by unacceptable toxicities, no marked potentiation of ISGs by tamoxifen could be identified, clinical evaluation of the combination was terminated.

Using beta-diketonate Ru precursors diluted in n-octane Ru and RuO"2 layers were grown on plane 200nm SiO"2/Si wafers by atomic vapor deposition (AVD^(R)). AVD^(R) was carried out in an AIXTRON Tricent^(R) system using liquid delivery of the ruthenium precursor. The deposited multi-crystalline smooth (RMS surface roughness

We address the problem of how to use a priori information of data symbols to improve signal-to-noise ratio (SNR) estimation. Digital transmission with binary phase-shift keying (BPSK) over additive white Gaussian noise (AWGN) channels serves as a background. At the receive side, both pilot and data symbols are used to estimate the SNR. In addition, we assume that a priori information of the data symbols is available. Our proposed estimator is then derived as an approximate solution of the maximum-likelihood (ML) approach. A significant improvement in the low-SNR regime over the corresponding estimator without a priori information is shown. Hence, an estimator that uses a priori information of data symbols is suitable to be embedded in iterative decoding schemes like, e.g., turbo decoding or turbo equalization. In addition, the Cramer-Rao lower bound (CRLB) for SNR estimators using a priori information of data symbols is derived

The remanent magnetization and the magnetic anisotropy energy of 5–16 monolayer (ML) epitaxial Fe films grown on GaAs(001) were quantitatively monitored in situ by superconducting quantum interference device magnetometry and ferromagnetic resonance as a function of oxygen exposure at 300 K. We find that at an oxygen dose of 10 L the perpendicular uniaxial anisotropy decreases by almost 50%, whereas the magnetization is decreased by 8% only in the case of a 5 ML Fe film. The fourfold anisotropy constant K4 and in-plane uniaxial anisotropy constant , however, remain unchanged. Low-energy electron diffraction spots of the Fe surface disappear after 6 L of oxygen, indicating a disordered Fe oxide growth. For exposures below 70 L we observe a reduction of the remanent magnetization irrespective of the film thickness. At exposures >70 L we find a faster decrease of the remanent magnetization for the thinner films which is attributed to the finite size effect and a thickness dependent surface roughness of the iron films, respectively. As evidenced by Auger electron spectroscopy and x-ray diffraction, the iron oxide is found to be FeO in the first stage of oxidation, transforming into γ-Fe2O3 at higher dosages (>1000 L).

Ribonuclease L (RNase L) is a latent single-stranded RNA-directed endoribonuclease that is activated on binding to short 2'-5'-linked oligoadenylates (2-5A), a feature that has led to its use in antisense therapeutic strategies. By attaching a 2-5A moiety to the 5' terminus of standard antisense oligonucleotides, it is possible to activate RNase L and guide it to specific RNAs for degradation. These 2-5A antisense chimeras have been used successfully to target a variety of cellular and viral RNAs. Telomerase is a nuclear ribonucleoprotein complex that elongates telomeric DNA and contributes to cellular immortalization. Telomerase is composed of a protein catalytic subunit and an RNA (hTR or TERC) component, both of which are critical for holoenzyme activity. We describe the characterization of 2-5A antisense chimeras targeting the hTR component of telomerase (2-5A antihTR). Newly designed 2-5A anti-hTR molecules were assayed for their abilities to selectively degrade hTR in a cell-free system. Of the five chimeras tested, one (RBI011) degraded hTR by 97%, and two others (RBI013 and RBI009) were also found to be highly active (73-76% degradation). The ability of transfected RBI011, and its homolog RBI254, to degrade hTR in cultured tumor cells was assessed by real-time RT-PCR. In these studies, RBI011 and RBI254 effectively degraded hTR in a variety of hTR-positive tumor cell lines. The hTR degradation studies were extended to growth assays to determine whether hTR ablation affected tumor cell viability or proliferation. RBI254 treatment resulted in reduced tumor cell viability over the course of 4-day growth assays, effects that were augmented by cotreatment with interferon-beta. To extend these results to an in vivo system, nude mice were implanted subcutaneously or orthotopically with hTR-positive prostate tumors and treated with RBI254. RBI254-treated mice exhibited enhanced tumor cell apoptosis and reduced tumor volume as compared with controls. These findings demonstrated the effectiveness of highly active forms of 2-5A antisense against hTR, and also highlight the usefulness of the cell-free system in predicting chimera efficacy before to inception of cell-based and in vivo studies.

Background. Reversal theory (Apter, 1982, 1989, 2001) is one of the motivational frameworks which attempts to examine human subjective experiences and behaviours. There are four dyads of metamotivational states (telic-paratelic, conformist-negativistic, autic-alloic, and mastery-sympathy) and individuals may prefer to be in one rather than the other of a dyad of states in a specific context such as sport participation (i.e. situational state balances). Aims. The purpose of this study was to examine the relationship between situational state balances and motives for sport and physical activity participation in adolescents using the theoretical framework of reversal theory. Their participation motives and the interacting factors of their situational state balances, gender, and level of participation were examined. Sample. Secondary school students (N = 1,235) aged about 14 to 20 years who participated in competitive or recreational sport completed the Participation Motivation Inventory (Gill, Gross, & Huddleston, 1983) to assess their motives for sport and physical activity participation, and the Apter Motivational Style Profile (Apter International, 1999) to assess their situational state balances. Methods. Factor analysis of the participation motives yielded factors to which MANOVAs and ANOVAs were applied with situational state balance, gender, and participation level as independent variables. Results. Factor analysis resulted in seven motive factors: status, team/friend, excitement/challenge, skill, energy release, fitness, and situational factors. MANOVAs and ANOVAs indicated significant differences in the sport motives between the situational state balances, genders, and levels of participation, and between pairs of situational state balance groups in males and females of competitive and recreational level. The autic-alloic dyad produced the strongest motive strength differences of the four pairs. Conclusions. The variable of situational state balances is significantly linked with participation motives in sport.

Ru and RuO"2 thin films for advanced metal gate applications were deposited on 200mm SiO"2/Si substrate by the novel deposition technique atomic vapor deposition (AVD(TM)). AVD(TM) was carried out in an Aixtron Tricent(TM) system using liquid delivery of the Ru precursor. The creation of Ru- and RuO"2-films is controlled by varying the O"2 flow and deposition temperature. Ru layers with a near bulk resistivity of 10@m@Wcm and a uniformity of ~2% for 20nm film thickness were obtained at 450^oC deposition temperature. The smooth Ru layers have a thickness uniformity of about 2% and a roughness

IL-2 therapy results in 10–20% response rates in advanced renal cell carcinoma (RCC) via activating immune cells, in which the protein tyrosine phosphatase Src homology 2 domain-containing phosphatase 1 (SHP-1) is a key negative regulator. Based on finding that sodium stibogluconate (SSG) inhibited SHP-1, the anti-RCC potential and action mechanism of SSG and SSG/IL-2 in combination were investigated in a murine renal cancer model (Renca). Despite its failure to inhibit Renca cell proliferation in cultures, SSG induced 61% growth inhibition of Renca tumors in BALB/c mice coincident with an increase (2-fold) in tumor-infiltrating macrophages (Mφ). A combination of SSG and IL-2 was more effective in inhibiting tumor growth (91%) and inducing tumor-infiltrating Mφ (4-fold), whereas IL-2 alone had little effect. Mφ increases were also detected in the spleens of mice treated with SSG (3-fold) or SSG/IL-2 in combination (6-fold), suggesting a systemic Mφ expansion similar to those in SHP-deficient mice. T cell involvement in the anti-Renca tumor action of the combination was suggested by the observations that the treatment induced spleen IFN-γ T cells in BALB/c mice, but failed to inhibit Renca tumor growth in athymic nude mice and that SSG treatment of T cells in vitro increased production of IFN-γ capable of activating tumoricidal Mφ. The SSG and SSG/IL-2 combination treatments were tolerated in the mice. These results together demonstrate an anti-Renca tumor activity of SSG that was enhanced in combination with IL-2 and functions via a T cell-dependent mechanism with increased IFN-γ production and expansion/activation of Mφ. Our findings suggest that SSG might improve anti-RCC efficacy of IL-2 therapy by enhancing antitumor immunity.

As part of a sport and exercise participation questionnaire, samples of Hong Kong high school students (n = 1,496) and high school students entering university (n = 862) completed the Motivational Style Profile (MSP; 4). In addition, 1,493 high school and 848 university entrants completed the MSP-SE, a sport and exercise version of the MSP. Students also completed six extra items related to general life motivational orientations (LMOs) and one other item relating to the frequency of their sport and exercise participation. Based on their answers to this latter item, students were divided into inactive, active, and very active groups and their metamotivational profiles tested for differences. MANOVA techniques produced several significant differences among activity groups in metamotivational dominance and state balance dimensions. The results are presented, and then they are discussed in terms of their implications for sport and exercise provision in high school, university, and more general contexts.

The purpose of this study was to examine motivational orientations of youth (N=1235) towards sport participation by using Achievement Goal Theory (AGT; Nicholls, 1989 ) and Reversal Theory (RT; Apter, 1989 ). Both theories are useful for determining how individuals varying in motivational orientations differ in their participation motives in the sport context. AGT postulates that individuals have task and ego orientations whereas RT assumes that individuals have eight orientations (telic, paratelic, conformist, negativistic, autic, alloic, mastery, and sympathy). Confirmatory factor analysis demonstrated overall good fit of seven underlying sport motive structures derived from the 30-item Participation Motivation Inventory ( Gill, Gross, & Huddleston, 1983 ). Subsequent canonical correlation analyses generally indicated a close relationship between motivational orientations and sport participation motives congruent with theoretical predictions in both AGT and RT. It was also found that task and ego orientations in AGT were linked with specific motivational orientations in RT. The results suggest that the two theories have similar motivational orientation constructs, more articulated in RT, which may be useful in examining what motivates youth to participate in physical activities and sport.

Previously, we have reported that overexpression of IHPK2 (inositol hexakisphosphate kinase 2) sensitized NIH-OVCAR-3 ovarian carcinoma cell lines to the growth-suppressive and apoptotic effects of IFN-beta (interferon-beta) treatment and gamma-irradiation. In the present study, we demonstrate that Apo2L/TRAIL (Apo2L/tumour-necrosis-factor-related apoptosis-inducing ligand) is a critical mediator of IFN-induced apoptosis in these cells. Compared with IFN-alpha2, IFN-beta is a more potent inducer of Apo2L/TRAIL and IHPK2 activity. Overexpression of IHPK2 converts IFN-alpha2-resistant cells into cells that readily undergo apoptosis in response to IFN-alpha2. In untreated cells transfected with IHPK2-eGFP (where eGFP stands for enhanced green fluorescent protein), the fusion protein is localized to the cytoplasm and perinuclear region. After treatment with IFN-beta, IHPK2-eGFP translocated to the nucleus. In cells transfected with mutant IHPK2-NLS-eGFP (where NLS stands for nuclear localization sequence), containing point mutations in the NLS, the fusion protein remained trapped in the cytoplasm, even after IFN-beta treatment. Cells expressing mutant NLS mutation were more resistant to IFN-beta. The IC50 value of IHPK2-expressing cells was 2-3-fold lower than vector control. The IC50 value of NLS-mutant-expressing cells was 3-fold higher than vector control. Blocking antibodies to Apo2L/TRAIL or transfection with a dominant negative Apo2L/TRAIL receptor (DR5Delta) inhibited the antiproliferative effects of IFN-beta. Thus overexpression of IHPK2 enhanced apoptotic effects of IFN-beta, and expression of the NLS mutant conferred resistance to IFN-beta. Apo2L/TRAIL expression and nuclear localization of IHPK2 are both required for the induction of apoptosis by IFN-beta in ovarian carcinoma.

Participants in this study were 1469 male and female students who specified a principal sport or physical activity that they had engaged in during the preceding year. They completed a sport and exercise participation questionnaire which contained a modified version of the Motivational Style Profile (MSP: Apter, Mallows, & Williams, 1998 ). This was used to determine respondents’ situational state balances. In addition, students responded to two sets of statements concerning (a) their reasons for participation (eight statements) and (b) their metamotivational orientation in life in general (six statements). Both sets of statements were formulated in the framework of reversal theory’s metamotivational states ( Apter, 2001 ). Respondents were grouped on the basis of the activity they had stated as their main sport or physical activity, as being relatively low in risk (e.g., aerobics, badminton, dance, hiking, tennis), medium in risk (e.g., athletics, fencing, life saving, netball, volleyball), or high in risk of physical injury (e.g., basketball, handball, judo, rugby, soccer). Significant overall differences in state balances were found for males (F(10,1252)=3.414, p=0.0012), but not for females (F(10,1448)=1.18, p=0.23), and in sport specific reasons for participation for both males (F(16,1246)=9.15, p=0.0001), and females (F(16,1470)=2.34, p=0.002). However, both male and female risk groups showed insignificant overall differences in life metamotivational orientations. The results are examined in the light of previous work and some of the implications for theory and practice are discussed.

Objective: The protocol was designed to examine the biological effects and clinical activity of interferon-β in patients with platinum/taxane-resistant ovarian cancer. Methods: Patients with resistant ovarian and fallopian tube cancers and primary peritoneal carcinoma were treated with recombinant human interferon-β (Rebif®, Serono International) at doses ranging from 6 to 24 million international units (MIU)/day, based on their tolerance to therapy. Levels of IP-10, an interferon-inducible protein, were measured in the serum to evaluate the biological effects of the drug. Also, the peripheral blood mononuclear cells and serum were examined for the induction of previously described novel regulators of interferon-induced death. Results: Eighteen patients were treated, of whom 9 (50%) could be treated at the highest dose level (24 MIU). The major toxicities were fever, chills and fatigue. The median duration of therapy was 6 weeks (range 1–22). No objective responses were observed. IP-10 levels were significantly increased, compared with baseline, at 2, 4, and 6 weeks after initiation of therapy (p < 0.01). Conclusions: Recombinant human interferon-β produced a definite biological effect in the serum of treated patients, but this outcome was not translated into any clinically observable or meaningful impact on the disease process.