Elevated CDCP1 predicts poor patient outcome and mediates ovarian clear cell carcinoma by promoting tumor spheroid formation, cell migration and chemoresistance

Hematogenous metastases are rarely present at diagnosis of ovarian clear cell carcinoma (OCC). Instead dissemination of these tumors is characteristically via direct extension of the primary tumor into nearby organs and the spread of exfoliated tumor cells throughout the peritoneum, initially via the peritoneal fluid, and later via ascites that accumulates as a result of disruption of the lymphatic system. The molecular mechanisms orchestrating these processes are uncertain. In particular, the signaling pathways used by malignant cells to survive the stresses of anchorage-free growth in peritoneal fluid and ascites, and to colonize remote sites, are poorly defined. We demonstrate that the transmembrane glycoprotein CUB-domain-containing protein 1 (CDCP1) has important and inhibitable roles in these processes. In vitro assays indicate that CDCP1 mediates formation and survival of OCC spheroids, as well as cell migration and chemoresistance. Disruption of CDCP1 via silencing and antibody-mediated inhibition markedly reduce the ability of TOV21G OCC cells to form intraperitoneal tumors and induce accumulation of ascites in mice. Mechanistically our data suggest that CDCP1 effects are mediated via a novel mechanism of protein kinase B (Akt) activation. Immunohistochemical analysis also suggested that CDCP1 is functionally important in OCC, with its expression elevated in 90% of 198 OCC tumors and increased CDCP1 expression correlating with poor patient disease-free and overall survival. This analysis also showed that CDCP1 is largely restricted to the surface of malignant cells where it is accessible to therapeutic antibodies. Importantly, antibody-mediated blockade of CDCP1 in vivo significantly increased the anti-tumor efficacy of carboplatin, the chemotherapy most commonly used to treat OCC. In summary, our data indicate that CDCP1 is important in the progression of OCC and that targeting pathways mediated by this protein may be useful for the management of OCC, potentially in combination with chemotherapies and agents targeting the Akt pathway.

Affected sibling pairs with juvenile idiopathic arthritis : An immunogenetic study of the disease in multicase families

Genetic susceptibility to juvenile idiopathic arthritis (JIA) was studied in the genetically homogeneous Finnish population by collecting families with two or three patients affected by this disease from cases seen in the Rheumatism Foundation Hospital. The number of families ranged in different studies from 37 to 45 and the total number of patients with JIA, from among whom these cases were derived, was 2 000 to 2 300. Characteristics of the disease in affected siblings in Finland were compared with a population-based series and with a sibling series from the United States. A thorough clinical and ophthalmological examination was made of all affected patients belonging to sibpair series. Information on the occurrence of chronic rheumatic diseases in parents was collected by questionnaire and diagnoses were confirmed from hospital records. All patients, their parents and most of the healthy sibs were typed for human leukocyte antigen (HLA) alleles in loci A, C, B, DR and DQ. The HLA allele distribution of the cases was compared with corresponding data from Finnish bone marrow donors. The genetic component in JIA was found to be more significant than previously believed. A concordance rate of 25% for a disease with a population prevalence of 1 per 1000 implied a relative risk of 250 for a monozygotic (MZ) twin. An estimate for the sibling risk of an affected individual was about 15- to 20-fold. The disease was basically similar in familial and sporadic cases; the mean age at disease onset was however lower in familial cases, (4.8 years vs 7.4 years). Three sibpairs (3.4 expected) were concordant for the presence of asymptomatic uveitis. Uveitis would thus not appear to have any genetic component of its own, separate from the genetic basis of JIA. Four of the parents had JIA (0.2 cases expected), four had a type of rheumatoid factor-negative arthritis similar to that seen in juvenile patients but commencing in adulthood, and one had spondyloarthropathy (SPA). These findings provide additional support for the conception of a genetic predisposition to JIA and suggest the existence of a new disease entity, JIA of adult onset. Both the linkage analysis of the affected sibpairs and the association analysis of nuclear families provided overwhelming evidence of a major contribution of HLA to the genetic susceptibility to JIA. The association analysis in the Finnish population confirmed that the most significant associations prevailed for DRB1*0801, DQB1*0402, as expected from previous observations, and indicated the independent role of Cw*0401.

Molecular phylogeny and biogeography of langurs and leaf monkeys of South Asia (Primates: Colobinae)

The two recently proposed taxonomies of the langurs and leaf monkeys (Subfamily Colobinae) provide different implications to our understanding of the evolution of Nilgiri and purple-faced langurs. Groves (2001) [Groves, C.P., 2001. Primate Taxonomy. Smithsonian Institute Press, Washington], placed Nilgiri and purple-faced langurs in the genus Trachypithecus, thereby suggesting disjunct distribution of the genus Trachypithecus. [Brandon-Jones, D., Eudey, A.A., Geissmann, T., Groves, C.P., Melnick, D.J., Morales, J.C., Shekelle, M., Stewart, C.-B., 2003. Asian primate classification. Int. J. Primatol. 25, 97–162] placed these langurs in the genus Semnopithecus, which suggests convergence of morphological characters in Nilgiri and purple-faced langurs with Trachypithecus. To test these scenarios, we sequenced and analyzed the mitochondrial cytochrome b gene and two nuclear DNA-encoded genes, lysozyme and protamine P1, from a variety of colobine species. All three markers support the clustering of Nilgiri and purple-faced langurs with Hanuman langur (Semnopithecus), while leaf monkeys of Southeast Asian (Trachypithecus) form a distinct clade. The phylogenetic position of capped and golden leaf monkeys is still unresolved. It is likely that this species group might have evolved due to past hybridization between Semnopithecus and Trachypithecus clades.

Lightcurve inversion for asteroid spins and shapes

Knowledge of the physical properties of asteroids is crucial in many branches of solar-system research. Knowledge of the spin states and shapes is needed, e.g., for accurate orbit determination and to study the history and evolution of the asteroids. In my thesis, I present new methods for using photometric lightcurves of asteroids in the determination of their spin states and shapes. The convex inversion method makes use of a general polyhedron shape model and provides us at best with an unambiguous spin solution and a convex shape solution that reproduces the main features of the original shape. Deriving information about the non-convex shape features is, in principle, also possible, but usually requires a priori information about the object. Alternatively, a distribution of non-convex solutions, describing the scale of the non-convexities, is also possible to be obtained. Due to insufficient number of absolute observations and inaccurately defined asteroid phase curves, the $c/b$-ratio, i.e., the flatness of the shape model is often somewhat ill-defined. However, especially in the case of elongated objects, the flatness seems to be quite well constrained, even in the case when only relative lightcurves are available. The results prove that it is, contrary to the earlier misbelief, possible to derive shape information from the lightcurve data if a sufficiently wide range of observing geometries is covered by the observations. Along with the more accurate shape models, also the rotational states, i.e., spin vectors and rotation periods, are defined with improved accuracy. The shape solutions obtained so far reveal a population of irregular objects whose most descriptive shape characteristics, however, can be expressed with only a few parameters. Preliminary statistical analyses for the shapes suggests that there are correlations between shape and other physical properties, such as the size, rotation period and taxonomic type of the asteroids. More shape data of, especially, the smallest and largest asteroids, as well as the fast and slow rotators is called for in order to be able to study the statistics more thoroughly.

Expected Performance of the ATLAS Experiment - Detector, Trigger and Physics

A detailed study is presented of the expected performance of the ATLAS detector. The reconstruction of tracks, leptons, photons, missing energy and jets is investigated, together with the performance of b-tagging and the trigger. The physics potential for a variety of interesting physics processes, within the Standard Model and beyond, is examined. The study comprises a series of notes based on simulations of the detector and physics processes, with particular emphasis given to the data expected from the first years of operation of the LHC at CERN.

Geometry changes induced by negative hyperconjugative interactions involving carbonyl and thiocarbonyl groups

MNDO geometry optimizations have been carried out on a series of acyclic and cyclic unsymmetrically disubstituted carbonyl and thiocarbonyl compounds. The C=X unit shows a consistent and often sizeable tilt towards one of the substituents, following the order O > Snot, vert, similarN > C > B. Reference ab initio calculations and available experimental results support the MNDO results. The effect, which is particularly dramatic in small rings, is attributed primarily to favorable negative hyperconjugative interaction between the lone pair on X and a low lying adjacent σ* orbital. Such an interaction can lead to highly distorted structures, including perhaps to a planar molecule with an inverted sp2 carbon center.

A study of phase separation in ternary alloys

We have studied the evolution of microstructure when a disordered ternary alloy is quenched into a ternary miscibility gap. We have used computer simulations based on multicomponent Cahn-Hilliard (CH) equations for c(A) and c(B), the compositions (in mole fraction) of A and B, respectively. In this work, we present our results on the effect of relative interfacial energies on the temporal evolution of morphologies during spinodal phase separation of an alloy with average composition, c(A) = 1/4, c(B) = 1/4 and c(C) = 1/2. Interfacial energies between the 'A' rich, 'B' rich and 'C' rich phases are varied by changing the gradient energy coefficients. The phases associated with a higher interfacial energy are found to be more rounded than those with lower energy. Further, the kinetic paths (i.e. the history of A-rich, B-rich and C-rich regions in the microstructure) are also affected significantly by the relative interfacial energies of the three phases.

Precoder Designs for MIMO Broadcast Channels with Imperfect CSI

[1] D. Tse and P. Viswanath, Fundamentals of Wireless Communication.Cambridge University Press, 2006. [2] H. Bolcskei, D. Gesbert, C. B. Papadias, and A.-J. van der Veen, Spacetime Wireless Systems: From Array Processing to MIMO Communications.Cambridge University Press, 2006. [3] Q. H. Spencer, C. B. Peel, A. L. Swindlehurst, and M. Haardt, “An introduction to the multiuser MIMO downlink,” IEEE Commun. Mag.,vol. 42, pp. 60–67, Oct. 2004. [4] K. Kusume, M. Joham,W. Utschick, and G. Bauch, “Efficient tomlinsonharashima precoding for spatial multiplexing on flat MIMO channel,”in Proc. IEEE ICC’2005, May 2005, pp. 2021–2025. [5] R. Fischer, C. Windpassinger, A. Lampe, and J. Huber, “MIMO precoding for decentralized receivers,” in Proc. IEEE ISIT’2002, 2002, p.496. [6] M. Schubert and H. Boche, “Iterative multiuser uplink and downlink beamforming under SINR constraints,” IEEE Trans. Signal Process.,vol. 53, pp. 2324–2334, Jul. 2005. [7] ——, “Solution of multiuser downlink beamforming problem with individual SINR constraints,” IEEE Trans. Veh. Technol., vol. 53, pp.18–28, Jan. 2004. [8] A. Wiesel, Y. C. Eldar, and Shamai, “Linear precoder via conic optimization for fixed MIMO receivers,” IEEE Trans. Signal Process., vol. 52,pp. 161–176, Jan. 2006. [9] N. Jindal, “MIMO broadcast channels with finite rate feed-back,” in Proc. IEEE GLOBECOM’2005, Nov. 2005. [10] R. Hunger, F. Dietrich, M. Joham, and W. Utschick, “Robust transmit zero-forcing filters,” in Proc. ITG Workshop on Smart Antennas, Munich,Mar. 2004, pp. 130–137. [11] M. B. Shenouda and T. N. Davidson, “Linear matrix inequality formulations of robust QoS precoding for broadcast channels,” in Proc.CCECE’2007, Apr. 2007, pp. 324–328. [12] M. Payaro, A. Pascual-Iserte, and M. A. Lagunas, “Robust power allocation designs for multiuser and multiantenna downlink communication systems through convex optimization,” IEEE J. Sel. Areas Commun.,vol. 25, pp. 1392–1401, Sep. 2007. [13] M. Biguesh, S. Shahbazpanahi, and A. B. Gershman, “Robust downlink power control in wireless cellular systems,” EURASIP Jl. Wireless Commun. Networking, vol. 2, pp. 261–272, 2004. [14] B. Bandemer, M. Haardt, and S. Visuri, “Liner MMSE multi-user MIMO downlink precoding for users with multple antennas,” in Proc.PIMRC���06, Sep. 2006, pp. 1–5. [15] J. Zhang, Y. Wu, S. Zhou, and J. Wang, “Joint linear transmitter and receiver design for the downlink of multiuser MIMO systems,” IEEE Commun. Lett., vol. 9, pp. 991–993, Nov. 2005. [16] S. Shi, M. Schubert, and H. Boche, “Downlink MMSE transceiver optimization for multiuser MIMO systems: Duality and sum-mse minimization,”IEEE Trans. Signal Process., vol. 55, pp. 5436–5446, Nov.2007. [17] A. Mezghani, M. Joham, R. Hunger, and W. Utschick, “Transceiver design for multi-user MIMO systems,” in Proc. WSA 2006, Mar. 2006. [18] R. Doostnejad, T. J. Lim, and E. Sousa, “Joint precoding and beamforming design for the downlink in a multiuser MIMO system,” in Proc.WiMob���2005, Aug. 2005, pp. 153–159. [19] N. Vucic, H. Boche, and S. Shi, “Robust transceiver optimization in downlink multiuser MIMO systems with channel uncertainty,” in Proc.IEEE ICC’2008, Beijing, China, May 2008. [20] A. Ben-Tal and A. Nemirovsky, “Selected topics in robust optimization,”Math. Program., vol. 112, pp. 125–158, Feb. 2007. [21] D. Bertsimas and M. Sim, “Tractable approximations to robust conic optimization problems,” Math. Program., vol. 107, pp. 5–36, Jun. 2006. [22] P. Ubaidulla and A. Chockalingam, “Robust Transceiver Design for Multiuser MIMO Downlink,” in Proc. IEEE Globecom’2008, New Orleans, USA, Dec. 2008, to appear. [23] S. Boyd and L. Vandenberghe, Convex Optimization. Cambridge University Press, 2004. [24] G. H. Golub and C. F. V. Loan, Matrix Computations. The John Hopkins University Press, 1996.

Some recent developments in solid state galvanic sensors

A critical revi<:w of the possibilities of measuring the ~artlal pressure of sulfur using solid state galvanic cells )'n;;cd on AgI, C" , B-alumina, CaO-Zr02' Na2S04-I and doped ;:":;, ,,,Ilil "Iltl ,,11: auxiliary "jectrodes are presentlOu. SOIll..., df tllc!iL' sYHtcmH h,}vu inherent limltntlol1$ when <:xl'o" ...d to environments contilining both oxygen and sulfur. Electrode polarization due to electronic conduction in the solid electrolyte is a significant factor limiting the ;lC'e,"'acy of isotlwrm:l1 cell",. The electrochemical flux of{lit' !'\)ndlwl Ill}: Ion LhnHO',h tht' ('!('ctrojyt(~ C:Ul },(,! llIinlnliz(,{j pfUjJL!f cell. dL:~) i.t',11. Noni!:iot.herm~ll cells \.Jlth temperaLure compensated reference electrodes have a number of advantages over thC'ir isothermal counterparts.

Influence of substrate temperature on the properties of oxygen‐ion‐assisted deposited CeO2 films

Substrate temperature and ion bombardment during deposition have been observed to modify significantly the optical and structural properties of dielectric thin films. Single‐layer films of CeO2 have been deposited by electron beam evaporation with simultaneous oxygen‐ion bombardment using a Kaufman broad beam ion source and maintaining the substrates at elevated temperature. A systematic study has been made on the influence of (a) substrate temperature in the range ambient to 300 °C, (b) ion energy in the range 300–700 eV, and (c) ion current density 100–220 μA/cm2 on optical properties such as refractive index, extinction coefficient, inhomogeneity, packing density, and structural properties. The refractive index increased with in increase in substrate temperature: ion energy up to 600 eV and ion current density. Homogeneous, absorption free and high index (2.48) films have been obtained at 600 eV, 220 μA/cm2 and at substrate temperature of 300 °C. The packing density of the films was observed to be unity for the same deposition conditions. Substrate temperature with simultaneous ion bombardment modified the structure of the films from highly ordered to fine grain structure.

Ab initio investigation of the elasticity and stability of aluminium

On the basis of the pseudopotential plane-wave (PP-PW) method in combination with the local density functional theory (LDFT), complete stress-strain curves for the uniaxial loading and uniaxial deformation along the [001] and [111] directions, and the biaxial proportional extension along [010] and [001] for aluminium are obtained. During the uniaxial loading, certain general behaviours of the energy versus the stretch and the load versus the stretch are confirmed; in each case, there exist three special unstressed structures: f.c.c., b.c.c., and f.c.t. for [001]; f.c.c., s.c., and b.c.c. for [111]. Using stability criteria, we find that all of these states are unstable, and always occur together with shear instability, except the natural f.c.c. structure. A Pain transformation from the stable f.c.c. structure to the stable b.c.c. configuration cannot be obtained by uniaxial compression along any equivalent [001] and [111] direction. The tensile strengths are similar for the two directions. For the higher energy barrier of the [111] direction, the compressive strength is greater than that for the [001] direction. With increase in the ratio of the biaxial proportional extension, the stress and tensile strength increase; however, the critical strain does not change significantly. Our results add to the existing ab initio database for use in fitting and testing interatomic potentials.

Comparación de alternativas de manejo de plagas convencional e integrado (MIP), en el cultivo de sorgo (Sorghum bicolor (L) Moench): en epoca de postrera, 2006

Este trabajo se realizó en el km 43 carretera Tipitapa – Masaya en las tierras del productor Agapito Ñurinda. Con el objetivo de generar información en el manejo de plagas y enfermedades en el cultivo de sorgo (Sorghum bicolor (L).Moench), durante la época de postrera. El diseño experimental utilizado fue Bloque Completo al Azar (BCA), con cuatro tratamientos y cuatro repeticiones: T1 Una aplicación de Cypermetrina y Benomil en etapa vegetativa y reproductiva (inicio de floración y llenado de grano) T1 (1 C + B), T2 Dos aplicaciones de Cypermetrina y Benomil en etapa vegetativa y reproductiva (inicio de floracion y llenado de grano) T2 (2C + B), T3 Una aplicación de Dipel y Caldo sulfoc��lcico en etapa vegetativa y reproductiva (inicio defloración y llenado de grano) T3 (1 D + Cs), T4 Dos aplicaciones de Dipel y Caldo sulfoc��lcico en etapa vegetativa y reproductivo (in icio de floración y llenado de grano) T4 (2 D + Cs). Las variables evaluados fueron: Porcentaje de daño fresco causado por el Gusano Cogollero (Spodoptera frugiperda J. E. Smith), Incidencia poblacional de Mosquita del sorgo (Stenoddiplosis sorghicola Coquillet), Incidencia poblacional de Chinche pata de hoja (Leptoglossus zonatus Dallas), Severidad de enfermedades foliares. Basadas en la escala propuesta por (Thakur, R. P., 1995), Severidad de mohos de la panoja, Rendimiento del grano. Determinado por la siguiente fórmula descrita por Barreto y Raun (1988). Se realizó análisis de varianza (ANDEVA). Para el gusano cogollero el análisis estadístico indica que no existen diferencias estadísticas entre los tratamientos evaluados, sin embargo existen diferencias en los porcentajes de daño en las diferentes fechas de muestreo, lo que significa que el porcentaje de daño de la plaga varió de una fecha a otra. Los menores porcentajes de daño fresco los presentó los tratamientos T1 (1 C + B), y T2 (2C + B). El análisis estadístico realizado para enfermedades indica que no hubo diferencia estadística entre los tratamientos, pero si diferencia en la severidad de las enfermedades entre las fechas de muestreos, sin embargo el T2 (2 C + Cs), resultó con el menor valor medio de severidad (2.7613). Análisis estadístico realizado.

轻微的机械作用对断裂源形态的影响

　俄罗斯科学院约费技术物理研究所提出了固体断裂的两阶段模型, 该模型不随断裂尺度变化。第一阶段为裂隙的积累, 其大小受限于构造单元的特征尺度, 当达到其阈值密度时, 就形成局部的断裂源, 此时过程进展加速, 并完成宏观断裂。当过程进展缓慢时, 研究轻微的作用下断裂源的状态就具有意义。

Disinfection of sea water by ultraviolet radiation

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