Comparison of estrogen receptor DNA binding in untreated and acquired antiestrogen-resistant human breast tumors

Preliminary studies have suggested that measuring the ability of immunoreactive 67-kDa estrogen receptor (ER) to bind DNA and form in vitro complexes with its cognate estrogen response element (ERE) might serve to identify breast tumors most likely to respond to antiestrogens like tamoxifen. Data from two different surveys of untreated primary breast tumors confirmed that only 67% (74 of 111) of ER-positive tumors express a receptor capable of forming ER-ERE complexes by gel-shift assay, with tumors of lower ER content having significantly reduced ER DNA-binding frequency (56%) relative to those of higher ER content (82%; P = 0.007). In contrast to these untreated tumors, a panel of 41 receptor-positive breast tumors excised after acquiring clinical resistance to tamoxifen during either primary (n = 26) or adjuvant therapy (n = 15) showed a significantly greater ER DNA-binding frequency, with nearly 90% capable of forming ER-ERE complexes (P < 0.02). To assess experimentally whether ER DNA-binding function is altered during the development of antiestrogen resistance, nude mouse MCF-7 tumor xenografts were analyzed before and after the acquisition of in vivo resistance to either tamoxifen or a pure steroidal antiestrogen, ICI 182,780. Tamoxifen-resistant MCF-7 tumors retained full expression of 67-kDa DNA-binding ER, and despite a markedly reduced ER content in the ICI 182,780-treated tumors, the expressed ER in these antiestrogen-resistant tumors exhibited full ability to form ER-ERE complexes. These findings indicate that breast tumors with acquired antiestrogen resistance continue to express ER of normal size and DNA-binding ability and suggest that the failure of antiestrogens to arrest tumor growth during emergence of clinical resistance results from an altered gene-regulatory mechanism(s) other than ER-ERE complex formation.     

Optimization of the structural properties of Hg1−x CdxTe (x = 0.18−0.30) alloys: Growth and modeling

The conditions for the metalorganic molecular beam epitaxial growth of Hg_1−xCd_xTe (x = 0.18−0.32) alloys at very low growth temperatures (T ≤150°C) have been optimized by correlating the surface properties and crystalline perfection with the incident Hg flux. A window for growth has been defined for x = 0.18, 0.23, and 0.32. A thermodynamic model has been developed to account for void formation. A neural net model has been used for the first time to model the dependence of void density on the Hg flux and the x-ray rocking curve widths on growth parameters. The combination of these two complementary modeling techniques allows for a flexible process optimization to be carried out with a minimum effort spent in calibration runs.     

Damping-limited modulation bandwidths up to 40 GHz in undoped short-cavity In/sub 0.35/Ga/sub 0.65/As-GaAs multiple-quantum-well lasers

We demonstrate record direct modulation bandwidths from MBE-grown In/sub 0.35/Ga/sub 0.65/As-GaAs multiple-quantum-well lasers with undoped active regions and with the upper and lower cladding layers grown at different growth temperatures. Short-cavity ridge waveguide lasers achieve CW direct modulation bandwidths up to 40 GHz for 6/spl times/130 /spl mu/m/sup 2/ devices at a bias current of 155 mA, which is the damping limit for this structure. We further demonstrate large-signal digital modulation up to 20 Gb/s (limited by the measurement setup) and linewidth enhancement factors of 1.4 at the lasing wavelength at threshold of /spl sim/1.1 /spl mu/m for these devices.     

Purification of OmpU from Vibrio cholerae classical strain 569B: evidence for the formation of large cation-selective ion-permeable channels by OmpU

The outer membrane of the classical Vibrio cholerae strain 569B was isolated by sucrose density centrifugation. The simple treatment of the isolated outer membrane or the cell envelopes with different detergents allowed the purification of two outer membrane proteins, the 38 kDa OmpU and the 25 kDa OmpV. Furthermore, a 35 kDa outer membrane protein (probably the 35 kDa OmpA-like protein) was purified by two-fold treatment of the cell envelope with 2% SDS solution. A subsequent wash of the SDS-pellet with 2% Genapol buffer yielded in the 38 kDa OmpU protein, which formed SDS-resistant oligomers (66 kDa). The Genapol pellet contained OmpV. Reconstitution experiments with lipid bilayer membranes demonstrated that OmpU was a channel-forming component, whereas OmpV had a small channel-forming ability if any. The OmpU channels appeared to be large and water-filled and had a single-channel conductance of about 2 nS in 1 M KCl for the monomer in a trimer, which means that they have a larger cross-section than enterobacterial porins. The channels showed rapid switching between open and closed configuration. They were slightly cation-selective, which suggests that they contain an excess of negatively charged amino groups.     

A Hoek–Brown criterion with intrinsic material strength factorization

Probably the most common failure criterion for rock masses is the Hoek–Brown (HB) failure criterion. The HB criterion is an empirical relation that extrapolates the strength of intact rock to that of rock masses. For design purposes, the HB criterion is often fitted using equivalent Coulomb failure lines. However, equivalent Mohr–Coulomb (MC) shear strength parameters cannot yield the same failure characteristics as the HB criterion. The curvilinear HB criterion automatically accommodates changing stress fields; the MC criterion does not. The extended HB criterion proposed in this paper provides a solution to this problem by incorporating an intrinsic material strength factorization scheme. The original HB criterion is additionally enhanced by adopting the spatial mobilized plane (SMP) concept, first introduced by Matsuoka and Nakai (MN). The SMP concept accounts for the experimentally proven, influence of intermediate principal stresses on failure, which is disregarded in the original HB criterion. A small set of examples provided at the end of the article gives a good indication of the merits of using the extended HB criterion in practical applications.     

Okavango River Bridge in Botsuana,Afrika – Elefantenzähne für den Okavango

Der Fluss Okavango im afrikanischen Botsuana mündet in ein inländisches Delta. Die dadurch entstehenden fruchtbaren Gebiete bilden die Grundlage für den einmaligen Artenreichtum der Flora und Fauna. Dies ist ein Anziehungspunkt für Touristen aus aller Welt. Zur Erschließung des nordöstlichen Teils des Deltas ist es geplant, die bestehende Fährverbindung durch eine feste Brückenverbindung als Schrägseilbrücke zu ersetzen. Um den Symbolcharakter des Bauwerks zu unterstreichen, wurden die Pylone in einer speziellen Gestaltungsidee als A‐Pylone in der Form von sich kreuzenden Elefantenzähnen entworfen. Es werden die Entwurfsgeschichte sowie wichtige Details der Konstruktion erläutert. Nach ihrer Fertigstellung wird die Okavango River Bridge die erste Schrägseilbrücke in Botsuana sein. Sie wird einen wesentlichen Beitrag zur Verbesserung und Entwicklung der Infrastruktur des Okavango‐Deltas leisten. Okavango River Bridge in Botsuana, Africa – Elephant tusks for the Okavango. The Okavango River in the African country Botsuana leads in a domestic delta. Due to the fact that the area is very fertile a unique species richness of flora and fauna has developed. This is a magnet for tourists from all over the world. For developing the north‐eastern part of the Delta, it is planned to replace the existing ferry service by a static link as a cable‐stayed bridge. To emphasize the symbolic character of the building the towers were designed in a special design idea as the A‐pylons in form of intersecting elephant tusks. It is the design history, as well as important details of the construction explained. After completion, the Okavango River Bridge will be the first cablestayed bridge in Botsuana. It will make a significant contribution to improving and developing the infrastructure of the Okavango Delta.     

The effects of sodium ricinoleate on small intestinal function and structure

The mechanism of hydroxy fatty acid-induced secretion was investigated in perfused hamster small intestine in vivo. Sodium ricinoleate at an 8-mM concentration resulted in not only secretion of water and sodium, but an increase in intestinal clearance of inulin and a 16,000 mol wt dextran as well. A concentration of ricinoleate (2 mM) which did not affect water transport, however, did not alter intestinal permeability. Ricinoleate-induced intestinal secretion was also accompanied by increased mucosal cell exfoliation as measured by the appearance of DNA in the perfusate and by apparent injury to epithelial cell membranes as judged by measurement of sucrase activity and phospholipid in cell-free aliquots of luminal fluid. Light and electron microscopic studies demonstrated substantial mucosal architectural changes with 8 mM ricinoleate with villus shortening and injury to epithelial cells at the villus tips. In contrast, cholera enterotoxin caused marked secretion of sodium and water, presumably by a cyclic AMP mechanism, but did not alter inulin clearance or enhance DNA or sucrase appearance in the lumen. These studies suggest that at least a component of ricinoleate-induced intestinal secretion is related to structural alterations of the mucosa.     

Properties and the cytoskeletal control of Ca(++)-independent large conductance K+ channels in neonatal rat hippocampal neurons

ABC transporters are a large superfamily of integral membrane proteins involved inATP-dependent transport across biological membranes. Members of this superfamily play roles in a number of phenomena of biomedical interest, including cystic fibrosis (CFTR) and multidrug resistance (P-glycoprotein, MRP). Most ABC transporters are predicted to consist of four domains, two membrane-spanning domains and two cytoplasmic domains. The latter contain conserved nucleotide-binding motifs. Attempts to determine the structure of ABC transporters and of their separate domains are in progress but have not yet been successful. To aid structure determination and possibly learn more about the domain boundaries, we set out to model nucleotide-binding domains (NBDs) of ABC transporters based on a known structure. Previous attempts to predict the 3D structure of NBDs were based solely on sequence similarity with known nucleotide-binding folds. We have analyzed the sequences of a number of nucleotide-binding domains with the algorithm THREADER, developed by D.T. Jones, and a possible fold was found in the structure of aspartate aminotransferase. We present a model for the N-terminal NBD of CFTR, based on the large domain of the A chain of aspartate aminotransferase. The model is refined using multiple sequence alignment, secondary structure prediction, and 3D-1D profiles. Our model seems to be in good agreement with known properties of nucleotide-binding domains and has some appealing characteristics compared with the previous models.     

ESR as a fast technique to dissolve nitrogen-rich inclusions in titanium

 Nitrogen-rich inclusions can lead to a reduction in fatigue life of highly stressed titanium-alloy components (found in the compressor sections of power generation gas turbines, turbine sections of power generation steam turbines, wing sections of aircraft air frames, and compressor and fan sections of aircraft jet engines, for example). It is the ”crack starting” nature of the nitrogen-rich inclusions that is the problem, not the presence of nitrogen in the system, per se. This paper covers the theory and laboratory experiments used to evaluate ESR (electro-slag refining) as an alternative technique for rapid dissolution of nitrogen-rich inclusions in titanium and titanium alloys. Five variations of melt rate, slag temperature and inclusion type were evaluated. One variant showed complete dissolution of the inclusions. Several of the other variants showed partial dissolution of the inclusions. The kinetics were observed to occur at a rate 100 to 1000 times faster than the rate of dissolution of nitrogen-rich inclusions by immersion in liquid titanium. Received: 14 December 1998 / Reviewed and accepted: 17 December 1998