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// Fabian Dominik Mairinger 1 , Claudia Vollbrecht 2, 3, 4 , Elena Flom 1 , Daniel Christian Christoph 5 , Kurt-Werner Schmid 1 , Jens Kollmeier 6 , Helmut Hans Popper 7 , Thomas Mairinger 8 and Robert Fred Henry Walter 1, 9 1 Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany 2 Institute of Pathology, Division of Molecular Pathology, Charite, Berlin, Germany 3 German Cancer Consortium (DKTK), Germany 4 German Cancer Research Center (DKFZ), Heidelberg, Germany 5 Department of Medical Oncology, West German Cancer Centre, University Hospital Essen, University of Duisburg-Essen, Essen, Germany 6 Department of Pneumology, Helios Klinikum Emil von Behring, Berlin, Germany 7 Department of Pathology, Division of Molecular Lung- and Pleurapathology, Medical University of Graz, Graz, Austria 8 Department of Pathology, Helios Klinikum Emil von Behring, Berlin, Germany 9 Ruhrlandklinik, West German Lung Centre, University Hospital Essen, University of Duisburg-Essen, Essen, Germany Correspondence to: Fabian Dominik Mairinger, email: fabian.mairinger@uk-essen.de Keywords: pleural mesothelioma, pemetrexed, thymidylate synthethase, folylpolyglutamate synthase, personalized therapy Received: October 12, 2016 Accepted: March 01, 2017 Published: March 21, 2017 ABSTRACT Background: Malignant pleural mesothelioma (MPM) is a rare tumor linked to a dismal prognosis. Even the most effective chemotherapeutical regime of pemetrexed combined with cisplatin leads to a remission-rate of only about 40%. The reasons for the rather poor efficacy remain largely unknown. Results: Phenotypes were significantly associated with progression (p=0.0279) and remission (p=0.0262). Cox-regression revealed significant associations between SLC19A1 / TYMS -ratio (p=0.0076) as well as FPGS / TYMS -ratio (p=0.0026) and OS. For differentiation by risk-groups, COXPH identified a strong correlation (p=0.0008). Methods: 56 MPM specimens from patients treated with pemetrexed were used for qPCR analysis. Phenotypes and risk groups were defined by their expression levels of members of the folic acid metabolism and correlated to survival and objective response. Conclusion: Our results indicate that the balance between folic acid uptake, activation and metabolism plays a crucial role in response to pemetrexed-based chemotherapy and the prognosis of MPM patients. Implementing this marker profile in MPM stratification may help to individualize MPM-therapy more efficiently.

Objectives Pulmonary adenocarcinomas (ADC) can be sub-grouped based on dominant oncogenic drivers. EGFR mutations define an entity of metastatic ADC with favorable prognosis and high susceptibility to EGFR tyrosine kinase inhibition. In contrast, the clinical impact of additional ERBB family members in ADC is less defined. To this end we prospectively studied HER2 expression, gene amplification, and mutation in relation to outcome of patients with advanced or metastatic ADC. Materials and methods Diagnostic tumor biopsies from 193 sequential patients with stage III/IV ADC were prospectively studied for HER2 expression by immunohistochemistry (IHC). Cases with IHC scores 2+ or 3+ were analyzed by HER2 chromogenic in situ hybridization (CISH), and sequencing of HER2 exons 20 and 23. Additional prospectively determined biomarkers included PTEN, cMET, pAKT, and pERK expression, KRAS , EGFR , BRAF and PIK3CA mutations, and ALK fluorescence ISH (FISH) . Results and conclusion HER2–IHC was feasible in 176 (91.2%) cases. Of 53 (30%) cases with IHC scores 2+/3+, 45 (85%) could be studied by CISH and 34 (64%) by sequencing. The lower number of HER2 -mutational analyses resulted from exhaustion of tumor tissue and DNA following mutational analysis of KRAS , EGFR , BRAF and PIK3CA . HER2 amplification was detected in 4 cases (2.3%), while no mutation was found. HER2 expression correlated with expression of pAKT and cMET. Expression of HER2 and pAKT was associated with favorable overall survival in stage IV disease. HER2-expressing ADC more frequently harbored KRAS mutations, while HER2 expression was absent in all 4 cases with BRAF mutation. HER2–IHC was not predictive of HER2 gene amplification or mutation, which both were rare events in prospectively studied patients with advanced or metastatic ADC. Expression of HER2 and pAKT define a population of patients with stage IV ADC with a distinct disease course, who could benefit from specifically tailored pharmacotherapies.

Glucose transporter-1 (GLUT-1) is one of the major isoforms of the family of glucose transporter proteins that facilitates the import of glucose in human cells to fuel anaerobic metabolism. The present study was meant to determine the extent of the anaerobic/hypoxic state of the intratumoral microenvironment by staining for GLUT-1 in intracranial non-embolized typical (WHO grade I; n = 40), brain invasive and atypical (each WHO grade II; n = 38) and anaplastic meningiomas (WHO grade III, n = 6). In addition, GLUT-1 staining levels were compared with the various histological criteria used for diagnosing WHO grade II and III meningiomas, namely, brain invasion, increased mitotic activity and atypical cytoarchitectural change, defined by the presence of at least three out of hypercellularity, sheet-like growth, prominent nucleoli, small cell change and “spontaneous” necrosis. The level of tumor hypoxia was assessed by converting the extent and intensity of the stainings by multiplication in an immunoreactive score (IRS) and statistically evaluated. The results were as follows. (1) While GLUT-1 expression was found to be mainly weak in WHO grade I meningiomas (IRS = 1–4) and to be consistently strong in WHO grade III meningiomas (IRS = 6–12), in WHO grade II meningiomas GLUT-1 expression was variable (IRS = 1–9). (2) Histologically typical, but brain invasive meningiomas (WHO grade II) showed no or similarly low levels of GLUT-1 expression as observed in WHO grade I meningiomas (IRS = 0–4). (3) GLUT-1 expression was observed in the form of a patchy, multifocal staining reaction in 76% of stained WHO grade I-III meningiomas, while diffuse staining (in 11%) and combined multifocal and areas of diffuse staining (in 13%) were only detected in WHO grades II and III meningiomas, except for uniform staining in angiomatous WHO grade I meningioma. (4) “Spontaneous” necrosis and small cell change typically occurred away from the intratumoral capillary network embedded within the pattern of GLUT-1 staining. Taken together, GLUT-1 staining cannot be applied as a substitute for histologic grading in order to predict tumor behavior. However, assessment of tumor hypoxia in association with “spontaneous” necrosis and foci of small cell change may substantially contribute to the neuropathologic diagnosis of WHO grades II and III meningioma.

Eine Magenschleimhautheterotopie ist im Rektum ein auserst seltener Befund. Es existieren 3 atiopathogenetische Hypothesen, wobei man heute von einer Fehldifferenzierung entodermaler Stammzellen ausgeht. Klinisch imponieren durch Salzsaurebildung zumeist peranale Blutabgange. Therapeutisch steht neben konservativ-medikamentosen Methoden die (endoskopische) Resektion im Vordergrund. Aus pathologischer Sicht erfordern Biopsien und Resektate solcher Lasionen auch aufgrund der grundsatzlich moglichen dysplastischen bzw. malignen Transformation eine sorgfaltige Begutachtung.

The Gamow–Teller strength distributions for the β decay of the ground state as well as the lowest excited states of the rp-process waiting point nuclei 68Se and 72Kr are obtained within the complex Excited Vampir variational approach using realistic effective interactions and a rather large model space. The shape mixing is consistently described for both the states in the even–even parent and the states in the odd–odd daugther nucleus. The influence of the shape mixing accounted by the different effective interactions used and comparison with the available data are presented. The possible influence of the decay of the lowest excited states of the parent nuclei in the astrophysical environment of X-ray bursts is discussed. Gamow–Teller strength distributions, β -decay half-lives, and β -delayed neutron emission probabilities for neutron-rich Zr nuclei are investigated for the first time within the complex Excited Vampir approach using a large model space. Comparison with available data and predictions relevant for the astrophysical r process are presented.

In conjunctival melanoma, little is known about the tumour biology and protein-expression patterns. In this study, the authors analysed the expression of the antiapoptotic oncoprotein B cell leukaemia/lymphoma-2 protein (Bcl-2), the tumour-suppressor phosphatase and tensin homologue deleted on chromosome ten (PTEN), and the heat-shock-protein HSP-90 in conjunctival melanoma (CoM) and conjunctival nevi (CoN) by immunohistochemistry (IHC).IHC was performed on 70 samples of CoM and 12 samples of CoN. Expression patterns between the diagnosis groups were compared. A receiver operating characteristic analysis was performed to determine the diagnostic value of the antigens.HSP-90 (p0.0001) and PTEN (p=0.001) showed the potential to differentiate between CoM and CoN. Bcl-2 expression was higher in CoM than in CoN (p=0.04). The loss of nuclear PTEN expression was more pronounced in the malignant melanomas than in CoN (p=0.02). Tumours located at unfavourable sites (fornix, palpebral conjunctiva, caruncle) that had developed recurrences expressed almost twice as much HSP-90 than recurrence-free tumours.Conjunctival melanocytes differentially express Bcl-2, HSP-90 and PTEN, depending on their entity. HSP-90- and PTEN expression may add relevant information for the differentiation between conjunctival melanoma and nevi.

In den letzten Jahren wurde durch Grundlagenforschung und translationale Forschung in der Onkologie eine Reihe von Biomarkern identifiziert, die fur Diagnostik, Staging, Prognoseabschatzung und als Ansatzpunkte fur individualisierte Therapien potentiellen klinischen Wert haben. Einige dieser Marker sind bereits in die klinische Praxis eingefuhrt, andere werden derzeit im Rahmen wissenschaftlicher Programme an Comprehensive Cancer Centers und innerhalb von Studiengruppen in ihrer Anwendung erprobt. Dieser Beitrag gibt einen Uberblick uber bereits klinisch etablierte Biomarker bei soliden Krebserkrankungen und einen Ausblick auf Kandidaten, die an der Schwelle zur breiten klinischen Anwendung stehen.

Hintergrund und Fragestellung Trotz aller Erfolge in der Transplantationsmedizin sterben in Deutschland jahrlich etwa 1000 Patienten wahrend der Wartezeit auf ein geeignetes Organ. Der chronische Mangel an Spenderorganen konnte durch eine Erhohung der Bereitschaft zur Organspende verbessert werden. Da die Mitarbeiter der Universitatskliniken unmittelbar an der Transplantationsmedizin beteiligt sind, ist ihre Meinung von besonderem Interesse bei der Analyse der Organspendebereitschaft.

We study the influence of shape mixing on the Gamow–Teller β decay of the nucleus 74Kr using the complex EXCITED VAMPIR variational approach for the description of the ground state of 74Kr and the 1 + states appearing within the β + -decay window in the daughter nucleus 74Br. The Gamow–Teller strength is obtained describing consistently the shape mixing in both parent and daughter nucleus. The theoretical results for the Gamow–Teller strength distribution as well as accumulated strength are compared with the available experimental data.

The complex Excited Vampir approach was applied to the description of the recently identified magnetic cascade of negative-parity states in the odd-odd 82Rb nucleus. Strong M1, ΔI = 1 transitions as well as rather weak crossover B(E2) strengths are obtained in agreement with the available data. The decrease of the B(M1) strengths with increasing spin is revealed by the calculations. A strong mixing of differently deformed states at the highest calculated spins is responsible for the trend of the B(M1;ΔI = 1) and B(E2;ΔI = 2) strengths.

Results are presented on shape coexistence effects in the nucleus 78Kr obtained within the complex version of the EXCITED VAMPIR variational approach. Oblate–prolate coexistence and mixing is found to be responsible for the characteristic features identified at low excitation energy for low and intermediate as well as high spins. At the highest investigated spins, the high density of configurations having different deformations results in the fragmentation of B(E2) strengths explaining the experimentally identified forking of the spectrum. The present investigation indicates the essential role played by particular neutron–proton matrix elements of the effective interaction on the oblate–prolate coexistence and mixing in the 78Kr nucleus.

We study the influence of Coulomb-induced isospin-mixing on the superallowed Fermi β decay using the complex EXCITED VAMPIR variational approach for the description of the lowest excited 0 + states in the two isovector triplets of nuclei 70 Se, 70 Br, 70 Kr and 74 Kr, 74 Rb, 74 Sr, respectively. As expected, the effects are small but nevertheless non-negligible. The calculated strength for the 74 Rb → 74 Kr Fermi β decay to the first excited 0 + state turns out to be very weak, in agreement with the experimentally given upper limit. However, particular non-analog Fermi branches to excited 0 + states with considerable strength are predicted to coexist with the superallowed decay in some of the presently investigated nuclei. This may give some hope for possible experimental detection.

Various variational approaches to the nuclear many-body problem are reviewed, which all use general symmetry-projected Hartree–Fock–Bogoliubov determinants as test configurations. The different approaches vary, however, in the degree of sophistication with which the underlying mean-fields as well as the configuration mixing are determined. The methods are explained in detail and their limitations are discussed. Special attention is payed to the particular symmetry restrictions made in the earlier applications and their consequences. Illustrative examples for some selected applications will be given, and the results, where possible, will be compared to those of alternative approaches. A calculational procedure, which allows one to use phenomenological density-dependent interactions, is reported and its merits and shortcomings are discussed. Finally, the problem of restoring Galilei invariance in the variational and similar approaches is adressed in some detail.

Results are presented on shape coexistence at low and high spins in the mirror nuclei 70 Se and 70 Kr obtained within the complex version of the Excited Vampir variational approach. Effects of oblate–prolate coexistence and mixing at low, intermediate and high spins are discussed. Strong M1, ΔI=0 transitions are predicted. A detailed comparison with the available experimental information is performed.

The effects of the restoration of Galilei invariance on many-nucleon states with one nucleon in the continuum are investigated within a simple knock-out model for quasi-elastic electron scattering using a Woods-Saxon partial-wave expansion for the continuum nucleon and simple Slater determinants for the bound states. For the total longitudinal response functions of the three nuclei 4 He, 16 O and 40 Ca, as seen in inclusive experiments, a rather good agreement of the Galilei-invariant prescription and the usual spectral-function approximation is obtained, provided that in the latter the momentum transfer is quenched by a factor (A - 1)/A, and furthermore relative motion wave functions are used for the various hole states. The agreement is worse if exclusive scattering is considered. Then the above modifications of the spectral-function approximation still yield the right positions and shapes for the partial longitudinal response functions of the various residual hole states. However, as expected from the different spectroscopic factors obtained for the Galilei invariant with respect to the normal approximation in the first of the present series of papers, for holes out of the last occupied shell the corrected spectral-function approach underestimates the Galilei-invariant strengths, while for holes from the lower shells a considerable overestimation of the strengths is observed.

Results are presented concerning shape coexistence and shape transition at low and intermediate spins in the N = Z nuclei 72 Kr, 76 Sr and 80 Zr obtained within the complex version of the Excited Vampir variational approach. The effects of possible contaminations due to the center-of-mass motion are discussed using a rough method to eliminate them at least approximately. The results indicate maximum influence on the observables depending on band mixing. Detailed illustration of the effects on the oblate–prolate mixing and the electromagnetic properties, as well as the alignments and particle occupations of the 0 g 9/2 spherical orbital is presented for the 72 Kr nucleus.

The ground state of the mid pf -shell nucleus 56 Ni is described in the framework of a symmetry-projected complex mean-field theory in which the desired symmetry properties are exactly projected from the most general Hartree–Fock–Bogoliubov type determinants. This few determinant method is applied for the first time in a full 1 p 0 f -shell model space. In the calculations the FPD6 effective interaction was used. It turns out that the use of only a few such generalized determinants is sufficient to give an excellent result. We compare the result with that of the quantum Monte Carlo approach, as well as with recently performed exact shell-model diagonalizations.

The effects of the restoration of Galilei invariance on many-nucleon states with one nucleon in the continuum are investigated within a simple knock-out model for quasi-elastic electron scattering using a Woods-Saxon partial-wave expansion for the continuum nucleon and simple Slater determinants for the bound states. For the total longitudinal response functions of the three nuclei 4He, 16O and 40Ca, as seen in inclusive experiments, a rather good agreement of the Galilei-invariant prescription and the usual spectral-function approximation is obtained, provided that in the latter the momentum transfer is quenched by a factor (A - 1)/A, and furthermore relative motion wave functions are used for the various hole states. The agreement is worse if exclusive scattering is considered. Then the above modifications of the spectral-function approximation still yield the right positions and shapes for the partial longitudinal response functions of the various residual hole states. However, as expected from the different spectroscopic factors obtained for the Galilei invariant with respect to the normal approximation in the first of the present series of papers, for holes out of the last occupied shell the corrected spectral-function approach underestimates the Galilei-invariant strengths, while for holes from the lower shells a considerable overestimation of the strengths is observed.

Results are presented concerning shape coexistence and neutron–proton correlations at low and high spins in the N=Z nucleus 56Ni obtained within the complex version of the Excited Vampir variational approach. The coexistence of small and moderately deformed oblate and prolate configurations, strongly mixed in some cases, may explain the irregularities observed for the yrast line, as well as the presence of other nonyrast states connected with them by E2 or Ml transitions. The first deformed band is well reproduced and predictions on the structure of next deformed bands are presented. These are the first microscopic calculations for 56Ni including in the model space the 0g9/2 and 1d5/2 spherical orbitals besides the full pf-shell. Contaminations due to the center of momentum motion are discussed and a rough method to eliminate them at least approximately is presented.

Total binding energies and yrast energy spectra of three selected 1p0f–nuclei have been calculated using an unrestricted Hartree–Fock–Bogoliubov approach with symmetry–projection before the variation. The full 1p0f–shell has been used as single–particle basis and the semi–empirical FPD6 interaction as effective Hamiltonian. The results are compared to those of truncated shell–model calculations performed with the OXBASH code. In the middle of the 1p0f–shell the variational method yields energy gains up to 4.5 MeV and thus proves to be far superior than the conventional truncation methods at least if in the latter only up to about 13000 configurations for each spin–isospin combination are admitted.

Results are presented on shape coexistence, shape transition and neutron–proton correlations at low and high spin states in the nuclei 72 Kr and 74 Kr. They have been obtained within the complex version of the Excited Vampir variational approach. Oblate–prolate coexistence and mixing at low spin is found to be responsible for the irregular sequence of states identified at low excitation energy. At high spins the coexistence of states with different prolate deformations results in complex multiple band structures. The present investigation indicates furthermore that particular neutron–proton matrix elements of the effective interaction play an essential role for the shape mixing.

The pair structure and the average pairing gaps of realistic wave functions obtained within the complex Excited Vampir variational approach are investigated in order to evaluate the neutron-proton pairing correlations at low and high spins in medium mass N ∼- Z nuclei. The number of isovector Jπ = 0+ pairs is calculated for the lowest few 0+ states in two chains of nuclei in the A ∼- 70 mass region. The results indicate the dominant role played by the isovector neutron-proton pairing correlations in the structure of odd-odd N = Z nuclei and the reduction of their importance with increasing neutron excess in even-even nuclei. The evolution of particular isovector and isoscalar pairs with increasing angular momentum is analyzed for the odd-odd N = Z nucleus 74Rb and the even-even N = Z nucleus 72Kr. It turns out that in the nucleus 74Rb the neutron-proton correlations play an essential role for the alignment of the yrast positive-parity even-spin band.

We review the theoretical interpretation of experimental results on low and high spin states in some even mass A=60−80 nuclei within the complex versions of the Excited Vampir and Fed Vampir variational approaches. The coexistence of oblate and prolate deformed configurations and their mixing at low spin are found to be responsible for the irregular sequences of states and the isomeric decays identified at low excitation energy in even-even nuclei. This behaviour is determined essentially by the isoscalar neutron-proton interaction. At higher spins the coexistence of states with different deformations causes complicated multiple band structures and strong fragmentation of the B(E2) strengths. It also influences the occurence of almost identical bands at normal deformation in some even mass nuclei. In some odd-odd nuclei the shape coexistence furthermore suggests a possible mechanism to populate high spin isomeric states. For the ground state properties of N=Z nuclei the competition between neutron-proton and like-nucleon isovector pairing plays an important role. With increasing angular momentum the neutron-proton alignment dominates the like-nucleon one in the ground bands of odd-odd N=Z nuclei while in the doubly even N=Z nuclei both types of alignment are of comparable importance.

Lifetimes of a superdeformed band in Sr-82 were measured with the centroid shift method. The measured average quadrupole moment of this band corresponds to a quadrupole deformation of beta(2) approximate to 0.49, which is slightly smaller than both the theoretical prediction, and the measured deformation of the SD band in the neighboring isotone Zr-84. Lifetimes of high spin states of three normally deformed rotational bands in Sr-82 were also measured with the Doppler shift attenuation method technique. The quadrupole moments of these normally deformed bands show a decrease at the highest spins, supporting the predicted band terminations.

Recent investigations of the shape transition and shape coexistence phenomena dominating the structure of the even-even N ≃ Z nuclei in the A ≃ 80 mass region are extended to the odd-odd nucleus 78Rb. Special attention is paid to the structure of some “identical” bands which have been recently identified in 78 Sr and 78Rb. The ground band of78 Sr and the yrast as well as excited negative parity bands in 78Rb are studied within the EXCITED VAMPIR approximation using complex Hartree-Fock-Bogoliubov transformations in a relatively large model space. The results are compared with the available experimental data. The emerging picture reveals the role played by the strong quadrupole deformation on the appearance of identical bands as well as the influence of the shape coexistence on their evolution. Predictions for the electromagnetic and alignment properties of the bands are presented.

The $\ensuremath{\beta}$-feeding probabilities for three important contributors to the decay heat in nuclear reactors, namely ${}^{102,104,105}$Tc, have been measured using the total absorption spectroscopy technique. For the measurements, sources of very high isobaric purity have been obtained using a Penning trap (JYFLTRAP). A detailed description of the data analysis is given and the results are compared with high-resolution measurements and theoretical calculations.

High spin negative parity states have been studied in 68 Ge via in-beam γ-ray spectroscopy at HHIRF. Several close-lying 7−, 9−, and 11− states are observed with a 13− to tentatively 17− cascade feeding them. Numerous E1 crossing transitions between the negative and positive parity levels are observed, along with possible M1 connecting transitions between the low lying negative parity bands. Previous microscopic calculations of the shape coexisting positive parity levels have been extended to the negative parity levels. The calculations used the EXCITED VAMPIR model based on complex HFB transformations with neutron-proton correlations and parity mixing in the mean field. The complex decay pattern and multiple high spin negative parity bands can be explained by a variable strength of mixing of the different deformed configurations which are bunched in small excitation intervals.

The recent investigations of the shape coexistence phenomena dominating the structure of even-even and odd-odd nuclei in the A ∼ 70 mass region are extended to N ⋍ Z nuclei ranging from krypton to molybdenum. Positive-parity states with even angular momenta in 72 Kr, 76 Sr, 78 Sr, 80 Zr and 84 Mo are investigated within the EXCITED VAMPIR approximation using essentially complex Hartree-Fock-Bogoliubov transformations and a relatively large model space. The results are compared with the available experimental data. We obtain an oblate ground band and strong oblate-prolate mixing for N = Z = 36, almost pure prolate and oblate bands, with the yrast one being prolate in 76 Sr, maximum prolate deformation in 76,78 Sr and 80 Zr with very high-lying non-yrast bands and decreased prolate quadrupole deformation for the N = Z = 42 system. Predictions for the electromagnetic properties of the investigated states are presented, too.

The biological behaviour of meningeal haemangiopericytomas was retrospectively studied using immunohistochemical staining with MIB1, a monoclonal antibody against the Ki-67 antigen, a nuclear protein related to cell proliferation. Paraffin-embedded material from 62 tumours from 40 patients were investigated. The proliferating compartment of the tumours was estimated by evaluating the MIB1 staining index, i.e. the percentage of MIB1 positive nuclei in at least 1000 counted tumour cells in representative areas. The staining index ranged from 1.24% to 39.01%. Statistical analysis revealed no significant correlation between the staining index and recurrence-free survival (chi 2 = 0.3922, P = 0.5311). Long-term observation (> 100 months), however, revealed a tendency to longer survival in the group with a staining index less than 5%. According to our results, the MIB1 staining index does not contribute to the accuracy of predicting the clinical outcome of meningeal haemangiopericytomas.

The levels in have been studied employing the pn) reaction with the Bucharest tandem and the p) reaction at 95 MeV with the HHIRF tandem to enhance high spin states. New high spin states have been observed beginning at 1179.5 keV and they include a cascade up to 6092.2 keV, tentatively assigned . These results are compared with the theoretical calculations based on the VAMPIR models which also include neutron - proton mixing.

High spin states in $^{68}\mathrm{As}$ have been studied using the $^{56}\mathrm{Fe}$${(}^{14}$N,2n${)}^{68}$As, $^{58}\mathrm{Ni}$ ${(}^{12}$C,pn${)}^{68}$As, and $^{46}\mathrm{Ti}$${(}^{25}$ Mg,p2n${)}^{68}$As reactions. New high spin states have been observed including a band structure above the known 2160 keV isomeric state. A microscopic description based on the EXCITED VAMPIR model for negative and positive parity states in $^{68}\mathrm{As}$ is presented. A possible mechanism to populate the observed high spin isomeric state is proposed. The complex structure of the $^{68}\mathrm{As}$ nucleus is caused essentially by specific shape coexistence effects. \textcopyright{} 1996 The American Physical Society.

A systematic numerical investigation of a recently developed nuclear structure approach is presented which diagonalizes the Hamiltonian in the space of the symmetry-projected Hartree-Fock-Bogoliubov (HFB) vacuum and symmetry-projected quasiparticle excitations with respect to it. The underlying HFB transformation, which is assumed to be time-reversal and axially symmetric, is determined by variation after the projection. The model allows the use of large basis systems. It has been applied to the calculation of energy spectra of several even-even, odd-odd and odd mass nuclei in the sd shell with mass numbers reaching from A=20 to 30. The Chung-Wildenthal interaction has been used. Good agreement with the exact shell model diagonalization and a considerable improvement on a previous approach, where the HFB transformation was significantly more restricted, is obtained., Comment: 21 pages LaTeX file, 2 LaTeX tables, 7 Postscript figures

In a previous study immunocytochemically detectable metallothionein (MT) expression in tumor cells of invasive duct carcinoma of the breast was shown to be associated with a more aggressive behavior and these findings have been subsequently confirmed by others. The aim of this study was to examine the prevalence and significance of MT positivity in preinvasive duct carcinoma in situ (DCIS). Fifty-five specimens of pure screen-detected DCIS were stained immunocytochemically for MT using the antibody E9. The intensity and distribution of MT staining were assessed using a semi-quantitative method resulting in intensity distribution (ID) scores allowing duct by duct analysis in relation to architectural and cytological features of the DCIS. In general, myoepithelial cells around benign and malignant structures stained uniformly strongly for MT. Staining in DCIS was analyzed by architecture irrespective of cytology and by nuclear grade irrespective of architecture. The results showed that MT staining was significantly greater in comedo (ducts with necrosis) DCIS (ID = 97) compared with noncomedo (ducts without necrosis) DCIS (ID = 56) ( P = .05 by Mann Whitney U statistic) and that low cytological grade (ID = 50) was associated with less MT staining than was high cytological grade (ID = 92) ( P = .05 by Mann Whitney U statistic). These observations thus are consistent with the previously observed association between MT positivity and more aggressive behavior in invasive duct carcinoma of the breast.

Translational and Galilean invariant approaches to the charge form factor for elastic electron scattering from nuclei as well as to the longitudinal and transverse response functions for inclusive electron scattering are presented. The results indicate that the proper treatment of these invariances is rather essential for the analysis of such experiments.