bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic Segregation to Mutant Mitochondrial DNA and Accompanying Loss of Mitochondrial DNA in Human NT2 Teratocarcinoma Cybrids
Authors: Turner Carrie J , Granycome Caroline , Hurst Rachel , Pohler Elizabeth , Juhola M Katariina , Juhola Martti I , Jacobs Howard T , Sutherland Lesley , Holt Ian J
Published: June 2005

In this study a well-characterized pathological mutation at nucleotide position 3243 of human mitochondrial DNA was introduced into human ρ0 teratocarcinoma (NT2) cells. In cloned and mixed populations of NT2 cells heteroplasmic for the mutation, mitotic segregation toward increasing levels of mutant mitochondrial DNA always occurred. Rapid segregation was frequently followed by complete loss of mitochondrial DNA. These findings support the idea that pathological mitochondrial DNA mutations are particularly deleterious in specific cell types, which can explain some of the tissue-specific aspects of mitochondrial DNA diseases. Moreover, these findings suggest that mitochondrial DNA depletion may be an important and widespread feature of mitochondrial DNA disease.
Mutational Analysis of the pH Signal Transduction Component PalC ofAspergillus nidulansSupports Distant Similarity to BRO1 Domain Family Members
Authors: Tilburn Joan , Sánchez-Ferrero Juan C , Reoyo Elena , Arst Herbert N , Peñalva Miguel A
Published: June 2005

The alkaline ambient pH signal transduction pathway component PalC has no assigned molecular role. Therefore we attempted a gene-specific mutational analysis and obtained 55 new palC loss-of-function alleles including 24 single residue substitutions. Refined similarity searches reveal conserved PalC regions including one with convincing similarity to the BRO1 domain, denoted PCBROH, where clustering of mutational changes, including PCBROH key residue substitutions, supports its structural and/or functional importance. Since the BRO1 domain occurs in the multivesicular body (MVB) pathway protein Bro1/Vps31 and also the pH signal transduction protein PalA (Rim20), both of which interact with MVB component (ESCRT-III protein) Vps32/Snf7, this might reflect a further link between the pH response and endocytosis.
The initial oxidation of beryllium by water vapor
Authors: Zalkind Shimon , Polak Micha , Shamir Noah
Published: June 2005

The initial stage of adsorption and beryllium oxidation by water (clearly a nonadiabatic process) was studied for a wide temperature range, using AES, XPS, DRS, and CPD measurements. The mechanism of room temperature (RT) oxidation by water vapor was found to be by nucleation and growth of 3 monolayer oxide islands, laterally spreading until coalescence takes place. When a full oxide layer is achieved, a further slow oxidation takes place, virtually stopping at ∼6 monolayer depth. Exposure of the surface to water vapor at 150 K yielded dissociation to H and OH, chemisorbed on the surface, as detected by an XPS chemical shift. The lack of such a shift at RT indicates a full dissociation of the water molecule on the surface. A giant effect of Be electron‐stimulated oxidation (ESO) by water vapor, as opposed to Be mild ESO by O2, was observed, reaching the maximal possible oxidation rate for the ratio of ≥150 impinging electrons per water molecule. It is suggested that the mechanism is a Mott—Cabrera‐like one, enabled by a combination of an electric field applied by negative OH and/or oxygen ions formed at the surface, probably by secondary electron attachment, and a very fast diffusion of Be2+ ions enabled by the presence of hydrogen in the oxide bulk. The water vapor ESO exhibits an inverse dependence on the substrate temperature, presumably due to the decrease with temperature of hydroxyl surface concentration, leading to the weakening of the electric field formed across the oxide.
Photophysics and photochemistry of ice films on graphite
Authors: Chakarov Dinko
Published: June 2005

We consider model systems consisting of submonolayer‐ to several monolayers‐thick ice films grown at ultrahigh vacuum (UHV) and low (from ∼15 K) temperatures on an atomically clean graphite (0001) surface. They are characterized experimentally with temperature‐programmed desorption‐isothermal desorption spectroscopy (TPD‐ITD) and high‐resolution electron energy loss spectroscopy (HREELS). We provide examples of how ice structure and chemical properties are altered by incoming photons. The phenomena of “photon annealing” of pure amorphous films and their structure‐selective laser ablation are discussed. In the case of water ice doped with alkali metals and coadsorbed with NO, we report on the observations of photoreactions taking place on the graphite/ice interface. Depending on the composition of the coadsorbed ice layer, irradiation leads to formation of H2, CH4, CO, NH3, and CO2. More specifically, we address the mechanisms of water photo‐dissociation at surfaces and interfaces with emphasis on the role of (i) perturbation of water molecules by coadsorbates and/or substrate; (ii) the light‐initiated electron (charge) transfer reactions leading to water splitting; and (iii) confinement of the precursor system and reaction products. In all examples the attention is on the operating mechanism for the transformations. The role of photo‐excited charge carriers in the graphite substrate is underlined. Increased understanding of photo‐stimulated reactions and processes involving water is needed to allow these processes to be effectively controlled and fully utilized.
Laser‐induced desorption of small molecules from oxide surfaces: A first‐principles study
Authors: Klüner Thorsten
Published: June 2005

Recent efforts in the theoretical simulation of laser‐induced desorption of small molecules from surfaces are summarized. As a representative example, photodesorption of CO molecules from a Cr2O3(0001) surface is investigated since detailed quantum state resolved experimental results are available for this system.

In particular, vectorial properties such as the alignment of the desorbing species are considered. Furthermore, the influence of surface temperature as a control parameter is investigated, and lateral velocity distributions are calculated and compared with experimental results.

All simulations presented in the present study are based on ab initio potential energy surfaces (PESs) for the electronic ground state as well as electronically excited states involved in the desorption process. These PESs provide the prerequisite for extensive high‐dimensional quantum mechanical simulations of the dynamics of nuclear motion based on a stochastic wave packet scheme.

These wave packet calculations allow for a detailed microscopic understanding of experimental results and provide a perspective for future experiments.
Time‐dependent density functional theory for nonadiabatic processes
Authors: Baer Roi , Kurzweil Yair , Cederbaum Lorenz S.
Published: June 2005

Time‐dependent density functional theory (TDDFT) is a general and robust method allowing the study of electron dynamics whether induced by nuclear motion or by external fields. We give a brief overview of the theory and some numerical methods together with recent applications stressing the generality and wide applicability of the method. We also discuss recent attempts to extend the present TDDFT by incorporating memory terms into the exchange correlation potentials.
Laser‐driven electron dynamics at interfaces
Authors: Saalfrank Peter , Klamroth Tillmann , Huber Christian , Krause Pascal
Published: June 2005

In this paper we present time‐dependent, quantum‐dynamical simulations of photoinduced processes at solid surfaces involving nonadiabatic transitions of electrons to and from short‐lived intermediate excited states. In particular, two‐photon photoemission (2PPE) spectra of naked metal surfaces and free‐standing metal films are considered. One major problem in both cases is the presence of electron—electron scattering, which is treated here in various ways. The first way is to adopt an open‐system density matrix approach, in which a single electron is weakly coupled to a “bath” of other electrons. The second approach is based on a many‐electron Schrödinger equation, which is solved with the help of a time‐dependent configuration interactions singles (TD—CIS) method.
Time‐resolved two‐photon photoemission at metal—dielectric interfaces
Authors: Berthold Wolfram , Höfer Ulrich
Published: June 2005

We review the influence of rare‐gas layers on image‐potential states at metal surfaces. Experiments on Xe, Kr, and Ar on Cu(100) and on Xe/Ru(0001) that use the technique of time‐resolved two‐photon photoemission are discussed. The energetic position of the electron affinity, the geometry of the adsorbate layer, and dielectric screening are the factors that influence the dynamical and energetic properties of the states. Theories on various levels are compared, including 1‐ and 3‐dimensional models and the GW approximation of many‐body theory. We also present new results on buried interface states that exist in the band gaps of both the Cu(100) substrate and a thick adsorbed Ar layer.
Theoretical study of halogen‐substituted benzene at a Si(111)7×7 surface
Authors: Petsalakis Ioannis D. , Theodorakopoulos Giannoula
Published: June 2005

The adsorption of halobenzene (for halogens F, Cl, Br, and I) on Si(111)7×7 was investigated using AM1 quantum mechanical calculations. First the 1,4‐cyclohexadiene type of chemisorbed structures with two C—Si bonds at C atoms 1 and 4 have been calculated. Generally, the calculated binding energy increases with the size of the halogen atom, in the series F, Cl, Br, and I. The sp2 carbon positions are the most favorable for the halogen atom, and for bromobenzene and iodobenzene there is significant additional stabilization for the geometry that allows interaction of the halogen atom with a nearby Si adatom. This stabilization hinders the transfer of the heavier halogen atoms, Br and I, to the surface. Other chemisorbed structures, involving formally divalent halogen atoms in a C‐X‐Si type of binding, have also been found to correspond to energy minima in the AM1 calculations. Furthermore, it was possible to calculate physisorbed structures for chlorobenzene and bromobenzene once the Si rest atoms were capped with H atoms. Two types of binding structures are suggested for chemisorption in excess of three molecules per half‐unit cell: one is a radical structure binding by a single C‐Si adatom bond, and the second one is binding by a single C‐X‐Si adatom interaction. Both of these singly‐bonded structures have been calculated to correspond to energy minima with binding energies smaller than the 1,4‐cyclohexadiene type of chemisorbed structure.
Photochemistry of molecules at confined environment: CD3Br/O/Ru(001) and CO2@Ice
Authors: Berger Raphael , Lilach Yigal , Ayoub Yousif , Asscher Micha
Published: June 2005

The photochemistry of molecules constrained within a confining environment on surfaces has been studied. Orientation of methyl bromide could be controlled methyl down or up by varying the pre‐adsorbed oxygen coverage due to electrostatic interactions on Ru(001) under UHV conditions. Irradiation of the coadsorption system at 193 nm has shown that the resulting photochemical activity is sensitive to the molecular orientation. Photodesorption and dissociation cross sections were 1.0·10−19 cm−2 for methyl‐down and 3.0·10−19 cm−2 for the methyl‐up configurations. This observation represents the first report of the steric effect in electron‐molecule interaction due to the dissociative electron attachment mechanism of photochemical processes on surfaces.

A second system of CO2 molecules caged within ice has also been studied. Here the trapped carbon dioxide molecules cannot leave the surface at their normal desorption temperature near 100 K, but are explosively desorbing at the onset of ice evaporation near 165 K. Upon UV irradiation, enhanced dissociation to adsorbed CO and oxygen is recorded. In addition, a new reactivity channel is observed to form H2CO, tentatively identified as formaldehyde. The relevance of photochemistry of caged molecules within ice to interstellar hydrocarbon formation as a possible route for the origin of life is discussed.
Electron transfer/transport at metal‐molecule interfaces probed by femtosecond time‐resolved two‐photon photoemission: Heptane and fullerene on Au(111)
Authors: Lindstrom Chad , Dutton Gregory , Quinn Daniel P. , Zhu Xiaoyang
Published: June 2005

Electron transfer and transport at metal‐molecule interfaces has been a central problem in a number of disciplines. There is renewed interest in this problem from the rapidly growing field of molecule‐based electronics, where the so‐called “contact problem” is usually probed in transport measurements. Here, we probe interfacial electron transfer/transport using time‐resolved two‐photon photo‐emission spectroscopy. Such an approach allows us to quantitatively measure the energetic alignment of occupied and unoccupied molecular orbitals to the metal Fermi level, the electronic coupling strength (or spectral density) between the molecular orbital and the metal substrate, and electronic‐nuclear coupling leading to dynamic localization. These three types of information are in fact key ingredients in quantitative theories for electron transfer and transport at molecule‐metal surfaces. Recent examples from our laboratory are used to illustrate the point. They include femtosecond dynamics of image potential resonances on heptane‐covered Au(111) and exciton relaxation dynamics in C60 epitaxial films on Au(111). On heptane/Au(111), the lifetime of the n = 1 image potential resonance increases from 52 fs at one monolayer (ML) coverage to 700 fs at 2 ML and 2.8 ps at 3 ML. On C60/Au(111), the Frenkel exciton (involving the LUMO+1 level) couples over long distance to the metal substrate, with lifetime of 350 fs at 30 ML to 80 fs at 2 ML coverage. The film‐thickness‐dependent decay dynamics in both cases can be attributed to interfacial electron transfer. Fitting the distance‐dependent electron transfer rates to a simple exponential function gives the characteristic distance parameter of ß = 0.6 ± 0.1 and 0.023 ± 0.005 Å−1 for heptane‐ and C60‐covered Au(111), respectively. The difference in the ß parameters illustrates the essential role of the electronic structure of molecules in mediating interfacial electron transfer/transport.
Langevin‐schroedinger formulation of electronic tunneling through a molecular bridge with a dissipative acceptor
Authors: Malka Alon , Peskin Uri
Published: June 2005

Modeling electronic tunneling through molecular bridges is desired in order to understand the mechanism of long‐range electron transfer reactions in nature, as well as for the design of novel molecular electronics devices. Particularly interesting is the effect of the nuclear motion at the molecular bridge on the electron transfer mechanism and rate. In this work we study the effect of electronic nuclear coupling at the molecular bridge on a unidirectional electronic tunneling process from an electron donor into a dissipative acceptor, as may appear in controlled electron transfer reactions at biological membranes, or in heterogeneous electron transfer reactions. The model includes a collection of harmonic bath modes coupled to the dissipative acceptor site and a single mode at the molecular bridge. The parameters of the dissipative bath are tuned such that the electronic population decays from the donor to the acceptor. This process is simulated using a time‐dependent nonlinear Langevin‐Schroedinger equation, based on a mean‐field approximation for the electronic‐nuclear coupling at the acceptor site and a numerically exact treatment of the electronic‐nuclear coupling at the molecular bridge. The simulations at zero temperature and weak electronic‐nuclear coupling demonstrate that electronic tunneling is promoted by coupling to the nuclear mode at the bridge. This result is consistent with our previous studies of electronic tunneling oscillations in a symmetric donor‐bridge‐acceptor complex, and it emphasizes the importance of electronic nuclear coupling in analyzing long‐range electron transfer processes through molecular bridges or wires.
Theoretical study of benzene, toluene, and dibromobenzene at a Si(111)7×7 surface
Authors: Petsalakis Ioannis D. , Polanyi John C. , Theodorakopoulos Giannoula
Published: June 2005

Theoretical Austin model 1 (AM1) calculations on the adsorption of benzene and toluene on Si(111)7×7 are presented. Both physisorbed and chemi‐sorbed states have been calculated for up to three adsorbed molecules per half unit cell of the Si(111)7×7 surface. Secondly, theoretical calculations on the induced attachment of benzene as well as rationalization of the dynamics of the halogenation reaction of 1,2‐ and 1,4‐dibromobenzene on Si(111)7×7 are reviewed. The main incentive for this study was the interpretation of recent experimental scanning tunneling microscopy (STM) results from the Toronto laboratory on a new electron‐induced or photo‐induced attachment process for benzene on Si(111), and, particularly, experimental results related to the thermal dissociative reactions of 1,2‐ and 1,4‐dibromobenzene on a Si(111)7×7 surface. The central objective is to relate the reagent geometry in 1,2‐dibromobenzene and 1,4‐dibromobenzene to the Br‐Br pair distance of dibrominated Si(111)7×7. For benzene, we propose a possible path for the conversion from the normal strained di‐sigma‐bound state (S) at Si(111) to a more strongly bound state (B) consisting of a phenyl plus an H‐atom adsorbed species. For 1,2‐ and 1,4‐dibromobenzene dibromination of silicon, evidence has been found for two mechanisms of reaction. One reaction pathway involves intermediate binding of the organic molecule on the Si surface through C‐Si bonds, analogous to the benzene S structure. The second dynamical pathway involves intermediate binding through weak Br. Si attachment followed by formation of pairs of covalently‐bound Br‐Si. The outcomes from the two dynamical pathways are consistent with the observed STM patterns for pairs of Br‐Si at Si(111) 7×7 due to the reaction of 1,2‐ and 1,4‐dibromobenzene.
ERβ is a potent inhibitor of cell proliferation in the HCT8 human colon cancer cell line through regulation of cell cycle components
Authors: Martineti Valentina , Picariello Lucia , Tognarini Isabella , Sala Silvia Carbonell , Gozzini Alessia , Azzari Chiara , Mavilia Carmelo , Tanini Annalisa , Falchetti Alberto , Fiorelli Gianna , Tonelli Francesco , Brandi Maria Luisa
Published: June 2005

Several strands of evidence indicate that oestrogens exert a protective role against the development of colon cancer through indirect and direct effects on colonic epithelium. Oestrogen receptor β (ERβ), the predominant ER subtype in human colon, is significantly decreased in colonic tumours compared with normal mucosa suggesting a potential role in the regulation of colon tumour growth.

To investigate this hypothesis we engineered human colon cancer ERα-negative HCT8 cells in order to obtain ERβ protein over-expression. Stably transfected cells were cloned and ERβ expression and functionality were monitored by RT-PCR, Western blotting and transactivation in an assay using oestrogen-responsive reporter constructs.

Over-expression of ERβ inhibited cell proliferation and increased cell adhesion in a ligand-independent manner. Its constitutive activation is possibly due to cross-talk with intracellular signalling pathways, as epidermal growth factor and IGF-I were able to induce ERβ transactivation.

A possible mechanism by which ERβ over-expression inhibits proliferation in HCT8 cells is by modulation of some key regulators of the cell cycle; there is a decrease in cyclin E and an increase in the cdk inhibitor p21CIP1. In fact, flow cytometry analysis provided evidence for blocking of the G1-S phase progression induced by ERβ over-expression. The magnitude of this effect was affected by the level of ERβ expression.

These results provide the first direct evidence that ERβ plays an important role in colon cancer as a regulator of cell proliferation through the control of key cell cycle modulators and arrest in G1-S phase transition. These findings are compatible with the hypothesis that the loss of ERβ expression could be one of the events involved in the development or progression of colon cancer.
RET/PTC-induced gene expression in thyroid PCCL3 cells reveals early activation of genes involved in regulation of the immune response
Authors: Puxeddu E , Knauf J A , Sartor M A , Mitsutake N , Smith E P , Medvedovic M , Tomlinson C R , Moretti S , Fagin J A
Published: June 2005

RET/PTC rearrangements represent key genetic events involved in papillary thyroid carcinoma (PTC) initiation. The aim of the present study was to identify the early changes in gene expression induced by RET/PTC in thyroid cells. For this purpose, microarray analysis was conducted on PCCL3 cells conditionally expressing the RET/PTC3 oncogene. Gene expression profiling 48 h after activation of RET/PTC3 identified a statistically significant modification of expression of 270 genes. Quantitative PCR confirmation of 20 of these demonstrated 90% accuracy of the microarray. Functional clustering of genes with greater than or less than 1.75-fold expression change (86 genes) revealed RET/PTC3-induced regulation of genes with key functions in apoptosis (Ripk3, Tdga), cell–cell signaling (Cdh6, Fn1), cell cycle (Il24), immune and inflammation response (Cxcl10, Scya2, Il6, Gbp2, Oas1, Tap1, RT1Aw2, C2ta, Irf1, Lmp2, Psme2, Prkr), metabolism (Aldob, Ptges, Nd2, Gss, Gstt1), signal transduction (Socs3, Nf1, Jak2, Cpg21, Dusp6, Socs1, Stat1, Stat3, Cish) and transcription (Nr4a1, Junb, Hfh1, Runx1, Foxe1). Genes coding for proteins involved in the immune response and in intracellular signal transduction pathways activated by cytokines and chemokines were strongly represented, indicating a critical role of RET/PTC3 in the early modulation of the immune response.
Negative Cognitions Predict the Course of Bipolar Depression, Not Mania
Authors: Johnson Sheri L. , Fingerhut Randy
Published: June 2005

Cognitive interventions for bipolar disorder have received increased attention, but very few prospective studies have focused on whether cognitive variables predict the course of bipolar disorder. Available studies have yielded conflicting results concerning the effects of negative cognitions on mania. In this study, 60 individuals with bipolar I disorder completed monthly symptom severity interviews. At a 6-month follow-up, they completed the Dysfunctional Attitudes Scale, the Negative Automatic Thoughts Questionnaire, and the Positive Automatic Thoughts Questionnaire. Participants then completed monthly symptom severity interviews for another 6 months. Cognitive scales were correlated with current depression and predicted increases in depression over time, but were not related to mania. Although results do not support negative cognitions as a predictor of mania, they do provide support for the increasingly common use of cognitive interventions to treat bipolar depression.
Dysfunctional Attitudes and Symptom Expression in Schizophrenia: Differential Associations With Paranoid Delusions and Negative Symptoms
Authors: Rector Neil A.
Published: June 2005

The extent to which dysfunctional attitudes reflecting excessive need for interpersonal acceptance and approval and/or unrealistic performance standards and interpersonal distance are associated with patterns of symptoms in patients with psychiatric disorders other than depression has been hypothesized but little tested. This study aimed to assess the relations among dysfunctional attitudes and symptoms of psychopathology in patients with DSM-IV-diagnosed schizophrenia (N = 56). The interpersonal and performance-related subscales of the Dysfunctional Attitudes Scale (Weisman & Beck, 1978) were assessed in relation to self-report and clinician-based symptom measures of psychosis, general psychopathology, and depression. The severity of paranoid ideation was found to be uniquely associated with elevated need-for-approval scores, whereas the constellation of negative symptoms was found to be uniquely associated with dysfunctional performance beliefs, even after controlling for depression severity. These results provide preliminary support for the importance of personality attributes in the particular expression of symptoms of psychosis.
Point-Counterpoint: Two Views on Traumatic Memories and Posttraumatic Stress Disorder
Authors: Brewin Chris R. , McNally Richard J. , Taylor Steven
Published: June 2005

Recent books by Brewin (2003) and McNally (2003b) each reviewed the empirical literature on traumatic memories and posttraumatic stress disorder (PTSD). Although these authors reached similar conclusions on several topics, they differed on a number of important and controversial issues. In this article, Drs. Brewin and McNally are interviewed on these issues, and asked to comment on one another’s conclusions. Issues discussed include the nature of traumatic events and traumatic stress responses, the problem of malingering in PTSD research, the relative merits of contemporary cognitive models of PTSD, the issues of whether body memories and satanic cult abuse are genuine phenomena, and the question of whether memories can be repressed and later recovered. Implications for the assessment and treatment of PTSD are also discussed. The arguments for and against the various opinions provide fertile ground for stimulating further research into these controversial topics.
Cover Picture: Synthesis of a Self‐Assembled Hybrid of Ultrananocrystalline Diamond and Carbon Nanotubes (Adv. Mater. 12/2005)
Authors: Xiao X. , Elam J. W. , Trasobares S. , Auciello O. , Carlisle J. A.
Published: June 2005

The cover shows self‐assembled hybrids of ultrananocrystalline diamond (UNCD) and carbon nanotubes (CNTs). These hybrids were successfully prepared by their simultaneous growth within an argon‐rich Ar/CH4 plasma, in work reported on p. 1496 by Carlisle and co‐workers. Various methods demonstrated the coexistence of UNCD and CNTs, and the capability of controlling the relative fraction and configuration of UNCD and CNTs in the hybrid material. This new synthesis pathway enables the development of new nanocarbons with unique mechanical, tribological, and electrochemical properties.
Dentatorubral‐pallidoluysian atrophy in three generations, with clinical courses from nearly asymptomatic elderly to severe juvenile, in an Australian family of Macedonian descent
Authors: Vinton Anita , Fahey Michael C. , O'Brien Terence J. , Shaw Janet , Storey Elsdon , McKinlay Gardner R.J. , Mitchell Peter J. , Du Sart Desirée , King John O.
Published: June 2005

We report a three‐generation Caucasian family of Macedonian origin with dentatorubral‐pallidoluysian atrophy (DRPLA), manifesting as very mild elderly onset, severe young adult onset, and severe childhood onset presentations in the three generations. The grandparental trinucleotide expansion size (52 repeats) is the smallest overtly pathogenic mutation yet reported. This 67‐year‐old man displayed only subtle neurological and cognitive deficits on formal examination and very slight signs on MRI. His son had developed a choreiform disorder at age 32 years, and by his 40s suffered severe dementia and motor decline. The grandson, the proband, presented as a teenager with progressive myoclonic epilepsy, dysarthria, ataxia, and cognitive decline, having manifesting learning difficulties from the age 5 years. Atrophin‐1 expansion sizes of 52, 57, and 66 repeats were demonstrated in the three patients, respectively. Given an absence of any other indicative history in the family, we speculate that the mutation may have expanded from a ‘high‐end’ normal allele to a pathogenic size at the grandfather's conception, or that one of his parents may have had a pathogenic mutation at the lowest end of the expanded range. © 2005 Wiley‐Liss, Inc.
Katalytische enantioselektive vinyloge Aldolreaktionen
Authors: Denmark Scott E. , Heemstra John R. , Beutner Gregory L.
Published: June 2005

Im Jahre 1935 formulierte R. C. Fuson das Prinzip der Vinylogie, um zu erklären, wie sich der Einfluss einer funktionellen Gruppe an einer entfernten Position im Molekül bemerkbar macht, wenn diese über konjugierte Doppelbindungen mit der Gruppe verbunden ist. In polaren Reaktionen ermöglicht dieses Konzept die Erweiterung des elektrophilen oder nucleophilen Charakters einer funktionellen Gruppe über das π‐System einer Kohlenstoff‐Kohlenstoff‐Doppelbindung. Diese vinyloge Erweiterung führt im Fall der Aldolreaktion zum Einsatz “erweiterter” Dienolether, die von γ‐enolisierbaren α,β‐ungesättigten Carbonylverbindungen abgeleitet sind. Seit 1994 sind einige Methoden für die katalytische enantioselektive vinyloge Aldolreaktion beschrieben worden, mit denen man unterschiedliche Regio‐ (Orts‐), Enantio‐ und Diastereoselektivitäten erzielen kann. In diesem Aufsatz werden die Bandbreite und die Einschränkungen dieser Transformation sowie ihre Anwendung in der Naturstoffsynthese diskutiert.
Catalytic, Enantioselective, Vinylogous Aldol Reactions
Authors: Denmark Scott E. , Heemstra John R. , Beutner Gregory L.
Published: June 2005

In 1935, R. C. Fuson formulated the principle of vinylogy to explain how the influence of a functional group may be felt at a distant point in the molecule when this position is connected by conjugated double‐bond linkages to the group. In polar reactions, this concept allows the extension of the electrophilic or nucleophilic character of a functional group through the π system of a carbon–carbon double bond. This vinylogous extension has been applied to the aldol reaction by employing “extended” dienol ethers derived from γ‐enolizable α,β‐unsaturated carbonyl compounds. Since 1994, several methods for the catalytic, enantioselective, vinylogous aldol reaction have appeared, with which varying degrees of regio‐ (site), enantio‐, and diastereoselectivity can be attained. In this Review, the current scope and limitations of this transformation, as well as its application in natural product synthesis, are discussed.
Planung und Bauausführung des Al‐Sadd Stadions in Doha, Katar
Authors: Stroetmann Richard , Albert Andrej
Published: June 2005

Das Stadion des Al‐Sadd Sports Club, dem renommiertesten Fußballklub des Emirats Katar, wurde in einem Zeitraum von rund 14 Monaten renoviert und in großen Teil en durch einen Neubau ersetzt. Der Beitrag berichtet über Besonderheiten bei der Planung und Bauausführung dieses Projekts. Auf die Stabilitätsberechnung des bogenförmigen Dachtragwerks wird detailliert eingegangen.
Lastansätze bei Tragfähigkeitsnachweisen im Holzbau
Authors: Schatz Tino
Published: June 2005

Das neue Sicherheitskonzept ist mit dem Weißdruck der DIN 1052 auch im Holzbau Stand der Technik geworden. Gerade die Nachweise im Grenzzustand der Tragfähigkeit bringen dabei die deutlichsten Veränderungen gegenüber dem bisherigen Vorgehen. Der vorliegende Beitrag soll als Arbeitshilfe dienen und das Nachweisverfahren für die wichtigsten Lastfälle transparenter und übersichtlicher machen.
Zum Lastabtragungsmechanismus von vorgespannten Auftriebsankern
Authors: Dührkop Jan , Grabe Jürgen
Published: June 2005

Zur Beurteilung des Lastabtragungsmechanismus von Auftriebsankern wird ein einfaches Ersatzfedermodell erstellt, mit dem sich eine Ankerprüfung nach DIN 4125 simulieren läßt. Die Untersuchung zeigt, daß aus einem nicht freigespülten Bohrloch eine Einschränkung der Ankerwirkung als Auftriebsanker resultieren kann und diese durch eine Prüfung der freien Ankerlänge nicht unbedingt aufgedeckt wird.
Über den Einfluß der Kornverteilungskurve auf das dynamische und das kumulative Verhalten nichtbindiger Böden
Authors: Wichtmann Torsten , Triantafyllidis Theodor
Published: June 2005

Dieser Beitrag präsentiert experimentelle Untersuchungen an nichtbindigen Böden zum Einfluß der Kornverteilungskurve auf die dynamischen Bodenkenngrößen sowie die Akkumulation von bleibenden Verformungen unter zyklischer Belastung. Es wird gezeigt, daß der dynamische Schubmodul nicht vom mittleren Korndurchmesser beeinflußt wird, mit steigender Ungleichförmigkeit jedoch stark abnimmt. Für einen ungleichförmigen Boden überschätzen die gebräuchlichen empirischen Formeln den dynamischen Schubmodul um bis zu 70%. Auch die bleibenden Verformungen unter zyklischer Belastung hängen signifikant von der Kornverteilungskurve ab. Diese sind umso größer, je feinkörniger der Boden ist. Ungleichförmige Böden verdichten sich unter zyklischer Belastung wesentlich schneller als gleichförmige Böden.
Specific interaction of chalcone‐protein: Cardamonin binding site II on the human serum albumin molecule
Authors: He Wenying , Li Ying , Liu Jiaqin , Hu Zhide , Chen Xingguo
Published: June 2005

Cardamonin (2′,4′‐dihydroxy‐6′‐methoxychalcone), one of the main constituents from the seeds of Alpinia katsumadai Hayata, belongs to chalcone with its antibacterial, antiinflammatory and other important therapeutic activities of significant potency and low systemic toxicity. In this article, the interaction of cardamonin to human serum albumin (HSA) has been studied for the first time by spectroscopic methods including Fourier transform infrared (FTIR) spectroscopy, circular dichroism (CD), and UV‐absorption spectroscopy in combination with fluorescence quenching under physiological conditions with drug concentrations of 0.67–4.0 μM. The results of the spectroscopic measurements and the thermodynamic parameters obtained (the enthalpy change ΔH0 and the entropy change ΔS0 were calculated to be –25.312 and 7.040 J·mol–1·K–1 according to the van't Hoff equation) suggest that hydrophobic interaction is the predominant intermolecular forces stabilizing the complex, which is also in good agreement with the results of the molecule modeling study. The alterations of protein secondary structure in the presence of cardamonin in aqueous solution were quantitatively calculated by the evidence from CD and FTIR spectroscopes with reductions of α‐helices of about 20%, decreases of β‐sheet structures of about 14%, and increases of β‐turn structures of about 15%. The quenching mechanism and the number of binding sites (n ≈ 1) were obtained by fluorescence titration data. Fluorescent displacement measurements confirmed that cardamonin binds HSA on site II. In addition, the effects of common ions on the constants of the cardamonin–HSA complex were also discussed. 2005 Wiley Periodicals, Inc. Biopolymers 79: 48–57, 2005

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Beneficial effect of silkworm hemolymph on a CHO cell system: Inhibition of apoptosis and increase of EPO production
Authors: Choi Shin Sik , Rhee Won Jong , Park Tai Hyun
Published: June 2005

To produce erythropoietin (EPO), Chinese hamster ovary (CHO) cells were first cultured in a medium containing FBS (growth medium) and then in a serum‐free medium containing sodium butyrate (production medium). Sodium butyrate increases recombinant protein production, but also induces apoptosis, which reduces cell viability and productivity. In a previous study, we found that silkworm hemolymph (SH), an insect serum, inhibits the apoptosis of insect and mammalian cells. To overcome sodium butyrate‐induced apoptosis, we added SH to growth medium. This pretreatment with SH inhibited the sodium butyrate‐induced apoptosis of CHO cells and consequently increased their longevity and their ability to produce EPO. As a result, the volumetric productivity of EPO was increased five‐fold. SH was found to inhibit cytochrome c release from mitochondria into the cytosol, and prevented the activation of caspase‐3 and other subsequent caspase reactions. © 2005 Wiley Periodicals, Inc.
A physiological product‐release model for baculovirus infected insect cells
Authors: Haas Richard , Nielsen Lars K.
Published: June 2005

Existing models describe the product release from baculovirus infected insect cells as an unspecific protein leakage occurring in parallel with protein production. The model presented here shows that the observed product release of normally non‐secreted proteins can be described through cell death alone. This model avoids the implicit non‐physiological assumption of previous models that cells permeable to recombinant protein as well as trypan blue continue to produce protein. © 2005 Wiley Periodicals, Inc.
Paclitaxel and pegylated‐liposomal doxorubicin are both active in angiosarcoma
Authors: Skubitz Keith M. , Haddad Philip A.
Published: June 2005

BACKGROUND

Paclitaxel has unique activity in angiosarcomas of the face and scalp, but its activity in angiosarcomas originating at other sites is less well defined. Paclitaxel and pegylated‐liposomal doxorubicin (PLD) are highly effective in Kaposi sarcoma (KS). Because of the efficacy of PLD in soft tissue sarcoma in general, and in KS in particular, coupled with potential similarities in KS and angiosarcoma, and the apparent activity of paclitaxel in angiosarcomas, the authors treated patients with angiosarcoma with either paclitaxel or PLD as initial chemotherapy.

METHODS

To better define the efficacy of these agents in angiosarcoma, the authors reviewed their experience with paclitaxel and PLD in patients with angiosarcoma treated between 1994 and 2004.

RESULTS

They identified seven patients with angiosarcoma treated with paclitaxel, and six treated with PLD. Only one patient in the series had an angiosarcoma of the scalp. Two patients receiving paclitaxel had received previous therapy with PLD, and four of six patients treated with PLD had previously received paclitaxel. Of the eight patients treated with paclitaxel, five had major responses (three had partial responses [PR] and two had complete disease remission [CR]) and three had progressive disease (PD). Of the 6 patients who received PLD, 3 had a PR for 6, 19, and >20 months, respectively, 2 had stable disease for 7 and 11 months, respectively, and 1 had PD.

CONCLUSIONS

The current study demonstrated the activity of PLD (five of six patients experienced clinical benefit) and extended the data on paclitaxel in angiosarcoma, both of the face and scalp, as well as angiosarcoma originating at other sites. Cancer 2005. © 2005 American Cancer Society.
Ovarian carcinoma screening in women at intermediate risk
Authors: Kauff Noah D. , Hurley Karen E. , Hensley Martee L. , Robson Mark E. , Lev Gali , Goldfrank Deborah , Castiel Mercedes , Brown Carol L. , Ostroff Jamie S. , Hann Lucy E. , Offit Kenneth , Barakat Richard R.
Published: June 2005

BACKGROUND

Women with family histories suggestive of an increased risk of ovarian carcinoma who have not had a deleterious BRCA1 or BRCA2 mutation identified are commonly suggested to consider ovarian carcinoma screening with transvaginal ultrasound and/or assessment of CA 125 levels. Limited information is available regarding the impact of this approach on either quality of life (QOL) or need for invasive follow‐up in this group of women.

METHODS

From November 1999 to October 2002, 184 women at intermediate risk of ovarian carcinoma were enrolled in a prospective study. Participants were screened with twice yearly transvaginal ultrasound and CA 125 assessments. Impact on QOL was measured using the Mental Component Summary (MCS) score of the Medical Outcomes Studies Short Form‐36. Need for invasive follow‐up was determined by questionnaire and medical record review.

RESULTS

In the current study, 135 participants underwent ≥ 1 follow‐up assessment. During a mean of 19.8 months of follow‐up, 12.9% of ultrasounds and 3.8% of CA 125 assessments were abnormal. The authors reported that 38.5% of participants had ≥ 1 abnormal ovarian screen that required a short interval follow‐up. Because of either abnormal bleeding or ultrasound abnormalities, 24% of participants underwent ≥ 1 endometrial sampling. Controlling for a history of breast carcinoma and menopausal status, abnormal ovarian screening results were associated with a decrease in MCS score (P = 0.034), whereas the need for endometrial sampling was not (P = 0.87).

CONCLUSIONS

Ovarian carcinoma screening in women at intermediate risk was associated with a substantial rate of abnormal screen results, endometrial sampling, and in women with abnormal ovarian screening findings, a decrease in MCS scores. These findings may have important implications for women considering ovarian carcinoma screening and for the design of future ovarian carcinoma screening trials. Cancer 2005. © 2005 American Cancer Society.
Immunosuppression and infectious complications in patients with stage IV indolent lymphoma treated with a fludarabine, mitoxantrone, and dexamethasone regimen
Authors: Tsimberidou Apostolia‐Maria , Younes Anas , Romaguera Jorge , Hagemeister Fredrick B. , Rodriguez Maria A. , Feng Lei , Ayala Ana , Smith Terry L. , Cabanillas Fernando , McLaughlin Peter
Published: June 2005

BACKGROUND

Myelosuppression and immunosuppression occur with purine analogs. The objective of the current study was to investigate the effects of combined fludarabine, mitoxantrone, and dexamethasone (FND) followed by interferon/dexamethasone on myelosuppression (absolute neutrophil counts), immunosuppression (CD4 and CD8 counts), and infectious complications in patients with previously untreated, Stage IV indolent lymphoma.

METHODS

Seventy‐three patients were treated. All patients received Pneumocystis carinii pneumonia (PCP) prophylaxis. CD4 and CD8 counts, serum immunoglobulin (Ig) levels, and neutrophil counts were correlated with infectious complications.

RESULTS

The median follow‐up was 6.1 years. Sixty of 73 patients had CD4, CD8, or Ig measurements. The median baseline CD4 count was 764/μL: This CD4 level decreased to 238/μL at 1 year and to 264/μL at 2 years; and it rose to 431/μL by 3 years and to 650/μL at 4 years. CD8 counts did not change significantly. The median baseline serum IgG level was 989 mg/d, decreased to 536 mg/dL at 1 year and to 693 mg/dL at 2 years, and it rose to 949 mg/dL at 3 years and to 1080 mg/dL at 4 years. Fourteen patients (19%) developed Grade 3–4 infections, the majority during FND therapy with neutropenia and/or accompanied by CD4 counts < 200/μL. CD4, CD8, and neutrophil counts did not differ between patients who developed Grade 3–4 infections, Grade 1–2 infections, or no infections.

CONCLUSIONS

Most infections with FND occurred during FND, in the setting of neutropenia, often with concurrent low CD4 counts. The overall safety profile for FND was good. However, patients should be monitored for opportunistic infections, and prophylactic antibiotics are recommended, particularly against PCP. Cancer 2005. © 2005 American Cancer Society.
Influence of the time between surgery and radiotherapy on local recurrence in patients with lymph node‐positive, early‐stage, invasive breast carcinoma undergoing breast‐conserving surgery
Authors: Benchalal Mohamed , Le Prisé Elisabeth , de Lafontan Brigitte , Berton‐Rigaud Dominique , Belkacemi Yazid , Romestaing Pascale , Peignaux Karine , Courdi Adel , Monnier Alain , Montcuquet Philippe , Goudier Marie‐Josèphe , Marchal Christian , Chollet Philippe , Abadie‐Lacourtoisie Sophie , Datchary Jean , Veyret Corinne , Kerbrat Pierre
Published: June 2005

BACKGROUND

Radiotherapy (RT) after breast‐conserving surgery (BCS) has produced significant reductions in ipsilateral breast carcinoma (BC) recurrence. It was shown previously that a delay in the initiation of RT resulted in a higher local recurrence (LR) rate. In the current retrospective analysis, the authors investigated whether the RT‐adjuvant therapy sequence modified local‐disease‐free survival (L‐DFS) after BCS in patients with early‐stage, lymph node‐positive BC.

METHODS

Among 7 French Adjuvant Study Group trials, 1831 patients were assessable, including 475 patients who received RT directly after BCS (95 patients received no adjuvant therapy, and 380 patients received hormone therapy), 567 patients who received RT after the third chemotherapy (CT) cycle (250 patients received 1–3 courses, and 317 patients received 4–6 courses), and 789 patients received RT after the sixth CT cycle. In the 1356 patients who received CT, the regimens consisted of fluorouracil 500 mg/m2; epirubicin 50 mg/m2, 75 mg/m2, or 100 mg/m2; and cyclophosphamide 500 mg/m2in 83.5% of patients.

RESULTS

After a median follow‐up of 102 months, 214 patients (11.7%) developed LR. The 9‐year L‐DFS rates were 92.0%, 81.5%, and 87.4%, respectively (P < 0.0001). It was worse in patients who received 1–3 CT cycles (P= 0.02). Patients who received hormone therapy were less likely to develop LR (P= 0.02). In the multivariate analysis, the timing of RT was not associated with a higher rate of LR, whereas tumor size > 2 cm and no hormone therapy were prognostic factors.

CONCLUSIONS

In the study population, there was no increase in the risk of LR when RT was delayed to deliver adjuvant CT. Prognostic factors were tumor size, and hormone therapy. The number of CT courses could modified this risk. Cancer 2005. © 2005 American Cancer Society.
Capecitabine plus oxaliplatin for the first‐line treatment of elderly patients with metastatic colorectal carcinoma
Authors: Comella Pasquale , Natale Donato , Farris Antonio , Gambardella Antonio , Maiorino Luigi , Massidda Bruno , Casaretti Rossana , Tafuto Salvatore , Lorusso Vito , Leo Silvana , Cannone Michele
Published: June 2005

BACKGROUND

In patients with metastatic colorectal carcinoma (MCC), capecitabine has demonstrated a superior response rate (RR), equivalent disease progression‐free (PFS) and overall survival (OS), and an improved overall tolerability profile compared with bolus 5‐fluorouracil/leucovorin (5‐FU/LV). The FOLFOX4 regimen, combining oxaliplatin with LV and bolus plus infusional 5‐FU (LV5FU2), has been shown to improve RR and PFS versus LV5FU2, and it was more effective and less toxic than irinotecan plus bolus 5‐FU/LV. Capecitabine (an oral fluoropyrimidine) may be an effective, well tolerated, and more convenient alternative to 5‐FU/LV in combination with oxaliplatin, especially in older patients.

METHODS

Elderly (≥ 70 years) patients with MCC were treated with a 3‐weekly regimen of oxaliplatin at an initial dose of 85 mg/m2intravenously on Day 1 plus capecitabine 1000 mg/m2orally twice daily from Days 2 to 15 (XELOX regimen). In the absence of Grade ≥ 2 hematologic toxicity, oxaliplatin was increased to 100 mg/m2in the second cycle, and in the absence of Grade ≥ 2 nonhematologic adverse events during Cycle 2, capecitabine was increased to 1250 mg/m2twice daily in the third and subsequent cycles. After the first 35 patients (first series), the treatment protocol was amended so that only an oxaliplatin increase to 110 mg/m2and 130 mg/m2during Cycles 2 and 3, respectively, was planned in the remaining 41 patients (second series).

RESULTS

Seventy‐six patients with a median age of 75 years (range, 70–82 years) entered the current study. In the first series, the oxaliplatin dose was increased in 18 (51%) patients, and the capecitabine dose was increased in 4 (11%) patients. In the second series, the oxaliplatin dose was increased to 110 mg/m2in 26 (63%) patients, and to 130 mg/m2in 19 (46%) patients. In all, 2 complete and 29 partial responses were observed, for an overall RR of 41% (95% confidence interval [CI], 30–53%). The median PFS was 8.5 months (95% CI, 6.7–10.3 months), and the median OS was 14.4 months (95% CI, 11.9–16.9 months). In a multivariate analysis, the presence of disease symptoms affected both PFS and OS, whereas OS also was independently affected by male gender and disease spread. Age had no independent effect on PFS or OS. Five percent of patients developed Grade ≥ 3 hematologic toxicity during treatment, Grade 3 peripheral neuropathy occurred in 8% of patients, and severe hand‐foot syndrome in 13% of patients.

CONCLUSIONS

Fit elderly patients with MCC showed a good RR to XELOX with only mild toxicity observed in most patients. XELOX, should, therefore be considered as an important therapeutic option for elderly patients with MCC. Cancer 2005. © 2005 American Cancer Society.