Giant lattice softening at a Lifshitz transition in Sr2RuO4.

The interplay of electronic and structural degrees of freedom in solids is a topic of intense research. More than 60 years ago, Lifshitz discussed a counterintuitive possibility: lattice softening driven by conduction electrons at topological Fermi surface transitions. The effect that he predicted, however, was small and has not been convincingly observed. Using a piezo-based uniaxial pressure cell to tune the ultraclean metal strontium ruthenate while measuring the stress-strain relationship, we reveal a huge softening of the Young's modulus at a Lifshitz transition of a two-dimensional Fermi surface and show that it is indeed driven entirely by the conduction electrons of the relevant energy band.

Advanced technique for measuring relative length changes under control of temperature and helium-gas pressure.

We report the realization of an advanced technique for measuring relative length changes ΔL/L of mm-sized samples under the control of temperature (T) and helium-gas pressure (P). The system, which is an extension of the apparatus described in the work of Manna et al. [Rev. Sci. Instrum. 83, 085111 (2012)], consists of two 4He-bath cryostats, each of which houses a pressure cell and a capacitive dilatometer. The interconnection of the pressure cells, the temperature of which can be controlled individually, opens up various modes of operation to perform measurements of ΔL/L under the variation of temperature and pressure. Special features of this apparatus include the possibility (1) to increase the pressure to values far in excess of the external pressure reservoir, (2) to substantially improve the pressure stability during temperature sweeps, (3) to enable continuous pressure sweeps with both decreasing and increasing pressure, and (4) to simultaneously measure the dielectric constant of the pressure-transmitting medium, viz., helium, εr He(T,P), along the same T-P trajectory as that used for taking the ΔL(T, P)/L data. The performance of the setup is demonstrated by measurements of relative length changes (ΔL/L)T at T = 180 K of single crystalline NaCl upon continuously varying the pressure in the range 6 ≤ P ≤ 40 MPa.

Kondo-like phonon scattering in thermoelectric clathrates.

Crystalline solids are generally known as excellent heat conductors, amorphous materials or glasses as thermal insulators. It has thus come as a surprise that certain crystal structures defy this paradigm. A prominent example are type-I clathrates and other materials with guest-host structures. They sustain low-energy Einstein-like modes in their phonon spectra, but are also prone to various types of disorder and phonon-electron scattering and thus the mechanism responsible for their ultralow thermal conductivities has remained elusive. Our thermodynamic and transport measurements on various clathrate single crystal series and their comparison with ab initio simulations reveal an all phononic Kondo effect as origin. This insight devises design strategies to further suppress the thermal conductivity of clathrates and other related materials classes, with relevance for thermoelectric waste heat recovery and, more generally, phononic applications. It may also trigger theoretical work on strong correlation effects in phonon systems.

The study of steroid hormones in epithelial ovarian tumours.

We examined the estradiol and testosterone content of 13 benign, 5 border-line and 26 malignant epithelial ovarian tumours with the aid of an indirect immunoperoxidase method. While the two hormones were rarely detected in the epithelium of benign tumours, they were frequently present in border-line or malignant tumours. In cases where the intersitial substance of the tumours was coupled to a glandular hyperplasia of the endometrium, estradiol predominance could be demonstrated. In the epithelial cells of malignant tumours of cytological grade 2 of the Broders grading system, which are of the highly differentiated and border-line types, the simultaneous presence of estradiol and testosterone is more frequent (4/5 and 6/9) than in poorly differentiated tumours of grades 3 and 4 (4/17). In the group of grade 2 with better prognosis, the tumour cells also contain estradiol. Similar tendency can be observed in patients with poorly differentiated tumours. Our observations refer to the possible prognostic value of the estradiol content of tumour cells.

Significance of histologic grading in the prognosis of ovarian tumors.

The prognostic significance of a histologic grading system was studied by an analysis of pathological specimens from 73 patients with ovarian epithelial cancers and tumors of borderline malignancies (tumors of low malignant potential) collected over a period of 25 years. The survival probability of patients in each group was analyzed by a computer program based on the product limit of Kaplan and Meier. The histologic grading scheme based on the presence of papillary formations or glands versus the presence of solid tumor nests proved to be prognostically significant for patients with stage I and II disease. The other grading system, based on cytologic features, was able to stratify survival rates into three instead of two groups distinguished by the histologic grading system. The survival of patients with moderately and poorly differentiated tumors was essentially the same. No difference was found between the prognoses of patients with cytologic grades 3 and 4.

Development and some characteristics of a P388 leukemia strain resistant to 1, 2:5, 6-dianhydrogalactitol.

Repeated intraperitoneal treatment of standard P388 mouse leukemia with dianhydrogalactitol (DAG) resulted in the development of a P388/DAG experimental mouse tumor which was resistant to the drug. Resistance was stable without DAG treatment throughout 80 passages. P388/DAG shows cross-resistance to alkylating agents such as nitrogen-mustard, cyclophosphamide and diacetyl-DAG but not to selected antimetabolites and tubulin binders and exhibits reduced sensitivity to nitrosoureas. Resistance to DAG could not be overcome by the administration of maximally tolerated dose of DAG to tumor bearing mice. The resistant tumor is one chromosome short and shows a 13-fold increase of cells possessing a submetacentric marker chromosome.

Rat liver-mediated degradation of dibromodulcitol.

The rate and extent of dibromodulcitol (DBD) conversion by 9000 g rat liver supernatant with an NADPH-generating system (S-9 mix) were studied using 3H-labelled drug. Results indicated that S-9 mix seemed to exert an initial protective effect delaying the solvolysis of DBD for about 30 min at 37 degrees C followed by rapid degradation into exclusively pharmacologically inactive products. Thus S-9 mix contained merely DBD as an effective agent; it amounted to less than 40% of the total radioactive compounds by 120 min. In the control mixtures the sovolytically produced effective drug content, i.e. the sum of DBD, 1,2-anhydro-6-bromo-6-deoxygalactitol (BrEpG), 1,2-5,6-dianhydrogalactitol (DAG) was 63%. Our results suggest the involvement of liver enzymes in the detoxification of DBD into inactive products. Therefore the antitumour effect of DBD cannot be attributed to its active BrEpG and DAG alone. The drug in its unchanged form may contribute to a somewhat greater extent to its cytostatic action than was believed before.

Cytochemical characterization of Yoshida sarcoma cells resistant to dibromodulcitol.

Two Yoshida ascites sarcoma cell populations, one of them originally sensitive and another rendered resistant to the alkylating agent dibromodulcitol (DBD), were compared for doubling time, labeling index, survival time, morphological features, cellular DNA content and modal DNA value. Cross-resistance studies were carried out on bilaterally growing solid tumours derived from the sensitive and resistant Yoshida cell populations. Glycogen-containing granules appeared in the cytoplasm of the DBD-resistant sarcoma cells; these were not present in the sensitive tumour. The growth parameters of the sensitive tumour were throughout the 10-day observation period characteristic of rapidly proliferating tumours, whereas those of the DBD-resistant tumour was characteristic of slowly proliferating systems. As compared to the mean DNA values for normal somatic cells (lymphocytes), those found for both tumours indicated that the cells were hyperdiploid aneuploid. The DNA stem line in the resistant tumour proved to be significantly smaller than that in the sensitive tumour. These results indicate that a reduction of malignancy in the Yoshida tumour is associated with a developed resistance to dibromodulcitol. The resistant tumour showing cross-resistance to dianhydrogalactitol, diacetyl-dianhydrogalactitol and to nitrogen mustard retained full sensitivity to cyclophosphamide and adriablastin (Adriamycin), and proved to be collaterally sensitive to vincristin.

Effect of phenobarbital on the toxicity and antitumor activity of dibromodulcitol and dianhydrogalactitol.

5-Ethyl-5-phenylhexahydropyrimidin-2,4,6-trione (phenobarbital) pretreatment significantly decreased the acute toxicity of 1,6-dibromo-1,6-dideoxygalactitol (dibromodulcitol) in H/Riop-Swiss mice and Wistar rats. Toxicity of dianhydrogalactitol, however, was not influenced to a considerable measure. Phenobarbital did not alter in itself the growth rate of the tumours examined. It significantly reduced, however, the antitumor activity of dibromodulcitol in NK/Ly-mouse lymphoma and Yoshida rat tumor. In contrast, the cytostatic effect of dianhydrogalactitol was not influenced at all by phenobarbital. The dissimilar effects of phenobarbital on the toxicity and anti-tumour activity of dibromodulcitol and dianhydrogalactitol are probably due to differences both in their metabolism and pharmacodynamics.

Amplification of optical activity by crystallization in the presence of tailor-made additives. The "inversion rule".

Experiments are described in which enantiomerically pure dimers, trimers and oligomers, generated from non chiral monomers by crystallization and topochemical reaction in suitably designed chiral crystals, induce preferential crystallization of the parent monomer in the enatiomorphous chiral phase of opposite absolute configuration. (We coin the term "inversion rule" for this effect). A general mechanism of amplification of optical activity by crystallization is proposed on the basis of these results, involving selective adsorption of resolved impurities on the surface of chiral crystals of similar stereochemistry, resulting in a decrease of the growth rate of the affected enantiomer and consequent preferential crystallization of the antipode. The implications of this mechanism to the generation and amplification of chirality in a closed system are discussed.

Complex evaluation of the effect of some cytostatic hexitol derivatives.

The antitumor effect of three structurally closely related alkylating hexitol derivatives (DBD, DAG, DiacDAG) was evaluated using a complex multi-parameter evaluation system. It comprised toxicology, action on ascites and solid tumors, as well as on subpopulations isolated by isopyknic centrifugation, cross-resistance and their action on chromatin components (DNA, histone, nonhistone proteins). The results indicate that in spite of their same mode of action, considerable differences could be observed in tumor specificity, inhibition of tumor growth and in their interaction with chromatin components. This multiparameter system seems to be very useful for comparative studies of other alkylating agents, especially for the evaluation of the effect of chemically closely related compounds.

Role of pesticides in hepatocarcinogenesis.

Pesticides are biologically active substances that are significant environmental contaminants. Only a few of the many pesticides have been subjected to short- or long-term carcinogenicity tests. To date, 16 of them have been identified as hepatocarcinogenic agents in animals, usually mice. However, their cancer-inducing effect in humans has not been completely proved. The use of short-term screening tests (first of all the Salmonella-microsome test) for routine screening of pesticides on a large scale is highly recommended. The herbicide 2,4,5-trichlorophenoxyethanol (TCPE) containing different amounts of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was tested for carcinogenicity in Swiss mice. TCPE enhanced liver tumors in males but TCDD did not affect liver tumor incidence. The occurrence of liver tumors was shown to be dose-dependent. There was no correlation between the results of in vivo carcinogenicity studies and the induction of aryl hydrocarbon hydroxylase and biphenyl 2-hydroxylase activities.

Chromosomal analysis on Yoshida tumor cells sensitive and resistant to dibromodulcitol.

Yoshida ascites tumor in Wistar rats was rendered resistant to dibromodulcitol. The modal number of chromosomes in the parent line was reduced from 39 to 36 in the resistant one. The parent tumor was a mixed cell population, containing large subtelocentric (LST) chromosome in 65 per cent of the cells, while in the remaining 35 per cent the LST chromosome was absent. In the resistant tumor line, however, the LST marker chromosome was present only in a few cells. The resistant line preserved this new karyotype throughout the 5 months of passaging even without dibromodulcitol, however, parallel to the loss of resistance this tumor line regained the original number of chromosomes, i. e. 39. Selection of a cell population with reduced number of chromosomes seems to be associated to the development of drug resistance.

[Clinical-pathological relationships of potenially malignant cystadenomas of the ovaries]. / Klinisch-pathologische Beziehungen der potentiell malignen Kystadenome der Eierstöcke.

A retrospective analysis of selected cases with ovarian tumours accumulated in our institute over a period of 20 years was done. Eight serous and 5 mucinous cystadenomas of borderline malignancy were reviewed. Out of the serous cystadenomas two led to death through recurrence, in other two instances the fatal outcome was caused by the transformation of the tumour to carcinoma. One of the mucinous cystadenomas was recurring. The progression of these tumours was relatively slow, manifesting 5 years after the first intervention. The relative favourable prognosis of ovarian cystadenomas with borderline malignancy seems to be supported by the observation that in the remaining 8 cases, radical surgery can ensure a 9 to 16 years survival time. The analysis of certain cases demonstrates that partial surgery can be performed only under adequate condition.