Synthesis of gonadotropin-releasing hormone III analogs. Structure-antitumor activity relationships

Following the observation that the activity of gonadotropin-releasing hormone III (GnRH-III) in the suppression of growth of MDA-MB-231 and MCF-7 breast cancer cells surpasses that of GnRH and other analogs thereof, analogs of GnRH-III were synthesized to investigate the structural basis for the improved antitumor activity. Compounds synthesized include analogs with changes in the central sequence in which GnRH-III differs from GnRH and in the C- and N-terminal regions. The results indicate that a salt bridge between Asp6 and Lys8 stabilizes the active conformation of GnRH-III and show the importance of the Trp7. Replacement of the C-terminal Gly-NH2 with D-Ala-NH2 was not well tolerated, but replacement with ethylamide was. Replacement of pGlu1 with Ac-D-Trp appears to have a significantly deleterious effect on a unique conformation of GnRH-III which is responsible for its binding to the receptors on cancer cell lines and the resultant antitumor activity.     

Structure-activity relationship studies of novel somatostatin analogs with antitumor activity

A series of new somatostatin analogs were synthesized in order to study the relative importance of specific substitutions in relation to selectivity between their endocrine and antitumor effects. Substitutions were carried out in all positions, except for Lys in position 5. Peptides were tested for their ability to inhibit in vitro and in vivo GH release, proliferation of the MCF 7 breast carcinoma cell line and tyrosine kinase activity in the HT 29 human colon carcinoma cell line. Selective biological activity was achieved in GH release and antitumor activity by the different amino acid substitutions. One of the analogs, with a five-residue ring (D-Phe-Cys-Tyr-D-Trp-Lys-Cys-Thr-NH2, TT-232), was unique. It had no GH release inhibitory activity, but did have strong tyrosine kinase inhibitory and antiproliferative effects.     

NON-RATIONAL ASPECTS OF PHOTOGRAPHIC MEANING

The main intent of this paper is to show how non-rational aspects of photographic meaning affect the interpretation of images. Three kinds of non-rational aspects of photographic meaning are investigated: authenticity, aesthetics and emotionality. The essential hypothesis of this study is that there is a duality in the non-rational aspects of photographic meaning that can be identified: Viewers can not only reflect the authenticity, aesthetics and emotionality of an image, but they can also reflect the authenticity, aesthetics and emotionality in an image. This process of self-reflection of a non-rational approach to images is considered a key component of photographic interpretation, which can uncover unconscious influences affecting each individual viewer. A photograph that won the Czech Press Photo contest for the year 2017 was chosen for a case study to show how the individual perception of authenticity, aesthetics and emotionality of photographic images affects its interpretation.     

Far Apart and Close Together: Fritz Haber and Chaim Weizmann

Fritz Haber (1868–1934) and Chaim Weizmann (1874–1952) were both prominent German-speaking Jewish chemists with rather divergent views on Jewish assimilation and Zionism that only converged upon the rise of the Nazis to power in Germany.  While Haber converted to Protestantism and followed the calling of a German patriot during World War One and the turmoil of the Weimar Republic, Weizmann became the leader of the Zionist movement whose efforts led to the founding of Jewish academic institutions in British Mandate Palestine and eventually to the creation of the State of Israel. Weizmann won the support of the British political establishment for the Zionist cause through his invaluable services to the British military as a chemist during World War One. Guided by the timeline of their encounters as well as their mutual correspondence, we trace the ever-closer relationship between these two towering figures of the 20th century. Had it not been for his ill health, Haber would have likely assumed a leading position at what is today the Weizmann Institute of Science in Rehovot as well as played a direct role in shaping other academic institutions, including The Hebrew University of Jerusalem, in the future State of Israel.     

Sensitivity study of BP-KX and B3 creep and shrinkage models

A numerical study of sensitivity analysis and statistical prediction of concrete creep average compliance function and shrinkage strain is presented. Two advanced models—the BP-KX and the B3—are studied. The influence of uncertainty of the basic input variables is taken into account by considering them as random variables. The statistical correlation is also treated in a simplified form for the assessment of its influence. Utilising the numerical simulation Latin Hypercube Sampling, the statistical and sensitivity analyses are performed. The results using different models are also compared. Two alternative measures of sensitivity analysis are utilised: sensitivity in terms of coefficient of variation and sensitivity in terms of nonparametric rank-order correlation coefficient. The strength of concrete and humidity appear as the most dominant factors with regard to the variability of results. Also, the estimations of distribution functions of the models are shown. They provide the possibility of establishing appropriate confidence limits. The significant difference in their ranges for the models in question is also shown.     

The tumor-selective somatostatin analog, TT2-32 induces a biphasic activation of phosphotyrosine phosphatase activity in human colon tumor cell line, SW620

Somatostatin has been demonstrated to activate phosphotyrosine phosphatases (PTPases) in pancreatic cells. In this work we studied the effect of a tumor-selective somatostatin structural derivative, TT2-32, on the PTPase activity in the SW620 human colon tumor cell line. TT2-32 caused a strong inhibition of cell proliferation. In response to TT2-32 we found a rapid and sustained increase (5-30 min) in PTPase activity showing two maxima at 0.1 and 30 microM concentrations, respectively. During short-term incubation tyrosine kinase activity was much less affected by TT2-32. TT2-32-induced activation of PTPases may be an important early step in the signaling cascade in the inhibition of cell proliferation in colon carcinomas.     

Redox protein noncovalent functionalization of double-wall carbon nanotubes: electrochemical binder-less glucose biosensor

Double wall carbon nanotubes are noncovalently functionalized with redox protein and such assembly is used for construction of electrochemical binder-less glucose biosensor. Redox protein glucose oxidase performs as biorecognition element and double wall carbon nanotubes act both as immobilization platform for redox enzyme and as signal transducer. The double carbon nanotubes are characterized by cyclic voltammetry and specific surface area measurements; the redox protein noncovalently functionalized double wall carbon nanotubes are characterized in detail by X-ray photoelectron spectroscopy, cyclic voltammetry, amperometry, and transmission electron microscopy.     

Ansatz zur Beurteilung von chloridbelasteten Stahlbetonbauwerken mit Bewertung der Restlebensdauer

Die Sicherstellung eines ausreichenden Zuverlässigkeitsniveaus im Rahmen der Erhaltung von Bauwerken und insbesondere Betonbrücken, welche durch Verkehrs‐ und Umwelteinflüsse einer kontinuierlichen Verschlechterung im Laufe ihrer Lebenszeit unterliegen, ist in der Regel eine komplexe und teure Aufgabenstellung. Besonders in Regionen mit Streusalzeinsatz in der Winterzeit beeinflusst die Chloridbelastung sowohl den Entwurf als auch die Erhaltung der Bauwerke durch ihren Einfluss auf die Dauerhaftigkeit wesentlich. In diesem Beitrag wird eine Bewertungsstrategie für die durch die Chloridbelastung hervorgerufene Zustandsverschlechterung von Betonstrukturen und deren Auswirkung auf das Sicherheitsniveau sowie die verbliebene Lebenszeit an einem Fallbeispiel vorgestellt. Hierbei werden die Entnahme von Proben, deren Untersuchung, die inverse Analyse des Eindringverhaltens und infolge die Prognose der Chloridkonzentration im Bauteil, die Vorhersage der Korrosionsentwicklung über die Zeit und schließlich die Bestimmung des gegenwärtigen und zukünftigen Zuverlässigkeitsniveaus unter Beachtung der normativ festgelegten Grenzzustände für Tragfähigkeit und Gebrauchstauglichkeit behandelt. Schlussendlich werden unterschiedliche Erhaltungsstrategien in Bezug auf die zu erwartenden Lebenszykluskosten verglichen. Approach for the Assessment of Concrete Structures Subjected to Chloride Induced Deterioration The maintenance of an adequate safety level of concrete bridges under their gradual degradation due to traffic and environmental actions during service life is an expensive, problematic and questionable task. Chloride ion ingress is an important aspect of durability design and maintenance, especially in regions where winter salt application for traffic safety is common, e. g. for highways. A feasible approach for the assessment of chloride induced deterioration and its consequences on the safety level, remaining service life and thus maintenance planning will be presented by a case study. Steps include the extraction of samples, laboratory test, inverse analysis and prognosis of chloride ingress, prediction of likely corrosion propagation over time and determination of the current and future safety level with regard to code based service limit states and ultimate limit states. Finally different maintenance strategies are compared with respect to the total life cycle costs.