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Background: The orphan surface receptor CDCP1 is over-expressed in various cancers and signals via Src family kinases (SFKs). It has been shown to be involved in anchorage independency of distinct tumors [Uekita et al. 2007; Moasser 2009]. Since CDCP1 is also speculated to be involved in tumor cell migration and invasion, the following study investigated the in vitro migration and invasion of breast cancer cell lines. In order to prove if lapatinib treatment might benefit CDCP1-positive but HER2/neu-negative breast cancer patients, we investigated the level of apoptosis after lapatinib application to different cell lines. Material and Methods: Four breast cancer cell lines were selected according to their CDCP1/HER-2/neu receptor expression (MDA-MB-231high/high; T47Dhigh/low; SKBR3low/high; MCF7neg./high). CDCP1 knock-down was achieved via nucleofection of Stealth™ RNAi (Invitrogen) against CDCP1. In vitro migration and invasion were analyzed for 48hs using trans-well assays (Merck). Migrated cells were labeled with Calcein AM and relative fluorescence units (RFU) were measured at 485/520nm. To investigate the effect of lapatinib, cells were cultured for 48hs in the presence of lapatinib (0,75 µM) as attached cells or as suspension culture on ultra-low adhesion plates, respectively. The enrichment of free nucleosomes was measured and compared between CDCP1-RNAi transfected and parental cells. Results: When transfected with CDCP1-RNAi, migration of SKBR-3 cells was not affected (96.2% migrating cells compared to control). However, CDCP1-RNAi-transfected MDA-MB-231 cells showed a strong reduction in migration (70.2% (± 21.5%)) compared to mock-transfected cells and the observed effect was even more impressive in T47D cells (58.3± 16.1% migration compared to control; P=0,011)). Invasion of CDCP1- silenced MDA-MB-231 was reduced to 71.4% (± 5.9%) of the mock-transfected control cells. Again, T47D cells also were severely impaired by CDCP1-knock-down (0.32 ± 0.02% of invasive cells compared to control; P Conclusions: The migratory activity of breast cancer cell lines did not strictly correlate with the degree in CDCP1 expression. However, CDCP1- knock down yielded in a clearly reduced migration and invasion of MDA-MB-231 cells and was even more impressive in T47D cell line. However, no effect was observed in SKBR3 cells. Thus, CDCP1 might represent one of a panel of surface receptors that participate in cell movement. However, Lapatinib was shown to have no effect on the viability of CDCP1pos./Her2/neuneg./low cells. Nonetheless, our study reveals that CDCP1 might have a strong impact on migration and invasive capacities of breast cancer cell lines and thus represents a potential target in more individualized breast cancer therapies. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-06-21.

The (1 × 1) and (√3 × √3)R30° (T4) structures of As adatoms on the Ge(111) and Si(111) surfaces are studied using first-principles calculations. Comparing the adsorption energies per As atom, we find that on the Si(111) surface, the T4 configuration is favored against the (1 × 1) structure by 0.5 eV per As adatom. The same preference is found on the Ge(111) surface, but only by 0.1 eV As adatoms. The (√3 × √3)R30° structure (13 ML coverage) is nevertheless unstable, and the energetics favor its transformation into domains with 1 ML coverage, and areas of a clean, reconstructed surface. The relaxed adatom structures and the redistribution of the electronic charge densities are also presented and discussed.

The ( 3 × 3 ) R 30° and (1 × 1) structures of Ga adatoms on Ge(111) and Si(111) surfaces are studied using first-principles calculations. Like on the Si(111) surface, the T4 structure is found to be more stable than the H3 structure on the Ge(111) surfaces within the ( 3 × 3 ) R 30° translational symmetry. Also, on both Ge(111) and the Si(111) surfaces, the T4 structure is energetically preferred over the (1 × 1) structure. However, the energy difference between the T4 and (1 × 1) structures for the Ge(111) surface (0.5 eV/Ga) is less than half of that for the Si(111) surface (1.3 eV/Ga). These results are corroborated by the corresponding redistributions of the electronic charge densities.

First-principles calculations based on the density-functional theory are performed to investigate the submonolayer coverage of Ga and B adatoms on a Ge(111) surface. We study the stability of the three different surface structures of adatoms, viz. the top-site (T4), the hollow-site (H3) and the substitution-site (S5). Calculations show that the T4 structure is favoured over the H3 structure for Ga adatoms and the S5 over the T4 for B adatoms. It is found that for Ga adatoms, the T4 structure induces a much longer range relaxation on the Ge(111) surface than the H3 one and for B adatoms in the T4 structure, no bond charge between adatoms and surface atoms is formed.

Intensities of the first‐ and second‐order Raman scattering in zincblende‐type semiconductors, under high hydrostatic pressure (P) and with laser energy below the fundamental gap, are analyzed. Theoretical description of the scattering efficiency and Raman cross section is carried out for optical and acoustic phonons in terms of electron‐one‐phonon and electron‐two‐phonon re‐normalized interaction Hamiltonians. The calculations show a good agreement with measurements performed on ZnTe, and explain the observed intensity decrease (increase) with pressure for LO and TO optical modes (2TA acoustic phonon). The theory presented contains the essential ingredients of the Raman scattering response, which allows, in combination with experimental data, to extract information on electron‐phonon interaction under hydrostatic pressure.

The (1×1) and (\(\sqrt 3 \times \sqrt 3 \))R30° (T4) structures of Ga and As adatoms on the Ge(111) and Si(111) surfaces are studied using the first-principles calculations. The surface energetics predicts, in some cases, a transformation of the T4 structure (surface covered with 1/3 monolayer (ML) of adatoms) into domains of the 1-ML covered (1×1) structure and areas of clean reconstructed surface. For As adatoms, such phase separation is favored on both substrates, while for Ga adatoms, it is only preferred on the Ge(111) surfaces. These results are compared with experimental observations.

Background: A crucial step in the metastatic cascade is to overcome anoikis, a type of programmed cell death after loss of cell-cell contact. CDCP1 has recently been indentified to be an essential prerequisite for anoikis resistance in lung adenocarcinoma cell lines [Uekita et al. 2007]. CDCP1 is overexpressed in distinct tumor tissues and suspected to signal via Src family kinases (SFK). Since CDCP1 overexpression has been detected in a variety of primary breast cancers and cell lines [Bühring et al. 2004], this study aimed at investigating the correlation between CDCP1 expression and anoikis-resistance in breast cancer cell lines and the involvement of SFKs.Material and Methods: Various breast cancer cell lines were tested for their CDCP1 status by FACS analysis and immunoblotting. CDCP1-negative breast cancer cell line MCF7 and primary normal breast cells were compared to the CDCP1-high cell lines MDA-MB-231 (∼90% positive cells (p.c.)), T47D (∼65% p.c.), SKBR3 (∼52% p.c.) and HBL100 (∼60% p.c.) when cultured in ultra low-adhesion culture plates. Apoptosis rate was evaluated measuring the nucleosome enrichment factor (EF). SFK-involvement was tested via proliferation analysis after treatment with SKF-inhibitor PP2 and its inactive derivate PP3. Since various types of breast cancer were influenced by the presence or absence of steroids, MDA-MB-231 cells and HBL100 cells were stimulated with ß17-Estradiol and CDCP1 expression was measured using relative quantification in qRT-PCR.Results: When grown in solution on ultra-low adhesion plates, CDCP1-negative primary normal breast cells underwent apoptosis (EF:5,29). CDCP1-high expressing MDA-MB-231 cells (EF:1,75) were less apoptotic than T47D (EF:3,68:) and SKBR3 cells (EF:4,35). However, CDCP1-negative MCF7 breast cancer cells were relatively resistant towards loss of anchorage (EF:2,03). When grown in suspension, proliferation rate of MDA-MB-231 is 6-fold lower than in normal tissue plates, both cultured with or without SFK-inhibitor PP2. Proliferation rate of CDCP1-negative MCF7 cells grown in solution in presence and absence of PP2 is even 24-fold reduced. MDA-MB-231 cells show a significant 50% reduction in RNA-levels of CDCP1 when cultured 48h in presence of ß17-ER (10-8M). However, in HBL100 cells, no change of RNA-level of CDCP1 was detectable.Conclusions: Anoikis resistance seems to directly correlate with the expression level of CDCP1, when cells are cultured in suspension. However, CDCP1-negative cell line MCF7 also shows relative resistance towards loss of anchorage. Thus, anoikis resistance may not be a monocausal phenomenon. Nonetheless, high level of CDCP1-expression also promotes cell proliferation in absence of anchorage to an extracellular matrix. RNAi-mediated knock-down will elucidate if CDCP1 is also involved in cell migration or invasion. Our studies show, that CDCP1-expression level has strong impact on the capacity of breast cancer cell lines to grow and survive anchorage independent - an essential prerequisite for metastatic potential. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6167.

It is shown how the variation of lattice dynamical force constants caused by substitutional isoelectronic impurities can be evaluated ab initio . The approach, illustrated on the example of Al in GaAs, is based on local density functional and uses ionic pseudopotentials of Al, Ga, As as the only input; Hellmann-Feynman theorem is applied in order to extract from self-consistent electronic charge densities the forces acting on atoms in periodic patterns in which entire planes of impurities are displaced. The defect-induced variations of inter planar force constants are converted into the inter atomic ones, which can be compared with those determined by phenomenological models from the measured local mode frequencies. A method is presented which allows to account for the effect of relaxation without requiring an explicit determination of the latter. Particular problems resulting from dealing with entire plane of defects are discussed and an estimate for relaxation is given.

It is shown that the macroscopic and microscopic dielectric responses to a constant electric field can be directly dealt with by a method which is general, alternative to linear-response theory, and not restricted to linear effects. The basic features of the theory are discussed; explicit calculations of the macroscopic dielectric constant, miccroscopic local fields, and transverse effective charges are presented for Ge and GaAs within the local-density functional theory.

Frequencies of the zone-centre and zone-boundary phonon modes in GaP are evaluated ab initio using the density-functional theory within the local-density approximation, with atomic numbers as the only experimental input. The norm-conserving pseudo-potentials are applied with Ceperley-Alder exchange and the plane-wave expansion formulation is used for calculation of total energy. Variation in the LO(X) and LA(X) frequencies at high and very high compressions is predicted. Eigendisplacements determined for the TO(X) and TA(X) modes are compared with the predictions provided by different phenomenological models which were developed for the lattice dynamics in the past.

Dispersion of eigenfrequencies and eigenvectors of lattice vibrations in Ge along the (110) direction is calculated from planar force constants, which are evaluated ab initio using the local density-functional theory and the pseudopotential scheme. The particularity of these vibrations is in the harmonic coupling between the longitudinal and transverse modes which is not predicted by group theory, even in high-symmetry crystals such as Ge. The formalism of lattice dynamics is systematically built in terms of the vibrating (110) planar sublattices-the form suitable for the ab initio determination of force constants-and it is shown how the coupled modes are to be treated in the planar representation. Particular attention is paid to anharmonicity of the vibrations, which the first-principles calculations provide as well. The results are used for comparison with predictions offered by different phenomenological models (i.e. shell model and bond-charge model) and for judging the physical realism of the latter.

The diffusion path of Li in γ-InSe is determined by means of total energy calculations. Neglecting relaxation effects we find that the most favourable diffusion path lies between the layers and has an activation energy and attempt frequency of 0.24 eV and 2.91 THz, respectively. The binding energy per Li is 2.53 eV.

Consideration of translational and rotational symmetry substantially reduces the number of Green's functions (elements of reciprocal dynamical matrix), which must be computed. In the present paper a method is proposed which further reduces this number by finding a set of linear equations for the Green's functions; these sets are given for b.c.c. and s.c. lattices. A method for approximate calculation of Green's functions is also proposed. Unter Berucksichtigung der Translations- und Rotationssymmetrie des Gitters kann man die Anzahl jener Greenschen Funktionen (der Elemente der reziproken dynamischen Matrix), die numerisch zu berechnen sind, wesentlich herabsetzen. In der vorliegenden Arbeit wird gezeigt, wie sich diese Anzahl durch Aufsuchen eines Systems linearer Gleichungen zwischen den Greenschen Funktionen noch weiter herabsetzen last. Fur die k.r.z. und einfach kubische Gitter werden diese Gleichungen angegeben. Ferner wird einer Methode fur die approximative Berechnung der Greenschen Funktionen vorgeschlagen.

The presented paper contains the tables of Green's functions for bcc lattices for outband frequencies 1·0≦ω/ωm≦1·6. The central-force model is used, the interaction with 8 nearest and 6 next-nearest neighbours is considered and the number of different Green's functions is fairly decreased by symmetry. Numerical difficulties arising by computing Green's functions are discussed. The derivation of symmetry relations for a dynamical matrix is generalized for the matrix of Green's functions.

The phonon spectrum of GaAs/AlAs superlattices along the (001) growth direction is calculated using a new approach based on a realistic unified treatment of the interactions in both bulk constituents, which naturally lends itself to dealing with superlattice geometries. Results for a (GaAs)3(AlAs)3 superlattice are shown with emphasis on different aspects of confinement.

Measurements of the phonon dispersion curves of Gas in the Ɖ → M and Ɖ → K → M directions by inelastic neutron scattering have been performed. They show a non dispersive behaviour of the LA phonons in both directions. A Rigid Ion Model (RIM) with anisotropic effective charges and Axially Symetric Forces (ASF) is constructed from these data and discussed.

It is shown how the density functional of Hohenberg-Kohn-Sham can be applied to phonon problems and it is demonstrated that the total energy can be calculated with an accuracy sufficient to “direct” evaluation of phonon frequencies: in this approach the energy of a “frozen phonon” is determined from its definition: by subtracting the total energy of crystal in equilibrium from that of a structure with phonon-induced displacements. Using local forms for the exchange-correlation operator and for the ionic pseudopotentials of Ga and As as the only approximations, we predict frequencies of phonons in GaAs at \(\overrightarrow {\text{k}} = \Gamma \) and X, as well as the respective Gruneisen parameters, which are in excellent agreement with experiment. Utility of Hellman-Feynman theorem is demonstrated and its application to phonon problems is discussed. A quantitative account of anharmonicities of the T0(Г) and TA(X) modes is given and a first-order phase transition to orthorhombic structure, driven by anharmonicity of the soft TA(X) mode, is predicted. The problem of the macroscopic electric field accompanying the L0(Г) mode is explained and it is shown how this field can be accounted for exactly in terms of dynamic effective charges; a method is given for a direct evaluation of the latter from the self-consistent pseudopotential corresponding to a structure with appropriately chosen displacement pattern. Ionic pseudopotentials used on GaAs are also applied to (pseudo-)atoms of Ga and As.