bluuebunny/crossref_metadata_2025 huggingface dataset:
Fine-Cutting Clio
Authors: Schama Simon
Published: February 2004

If you want to produce an epic fifteen-part series that moves television history into the common culture, dare you do it with a single scriptwriter who also appears on camera as "presenter" and with no other talking heads? Can plural consensus on television be traded in for the immediacy of a single interpreter? Simon Schama did this for the BBC and The History Channel in his A History of Britain and beat the ratings for The Simpsons. He narrates the story of this challenge in "Fine Cutting Clio."
The Reel Joan of Arc: Reflections on the Theory and Practice of the Historical Film
Authors: Rosenstone Robert A.
Published: February 2004

Although historians in recent years have become interested in evaluating the contributions of historical film to our understanding of the past, they have so far evolved no criteria for doing so. This essay moves toward doing just that by suggesting and examining some of the ways in which the dramatic historical film creates the world of the past on the screen. Operating metaphorically and poetically, the film set in the past becomes a work of history when it engages the ongoing discourse surrounding its subject, asking the kinds of questions historians ask, but answering them in a dramatic and semifictional way.
Creating the Twenty-First-Century "Historian For All Seasons"
Authors: Herman Gerald
Published: February 2004

In "Creating the Twenty-first Century 'Historian For All Seasons,'" the author traces the development of the divide between historians and media producers, and the impacts that this has on the public's awareness of the work historians do and on the historian's ability to influence the public. To heal this breach, he argues, just as the training of historians has adjusted to accommodate the need for expertise in content-related methodologies, so it must now adjust to permit historians to develop presentation-related skills in order to reach wider audiences and reclaim the centrality of historians to the understanding of the past.
Brachydactyly type C caused by a homozygous missense mutation in the prodomain of CDMP1
Authors: Schwabe Georg C. , Türkmen Seval , Leschik Gundula , Palanduz Sukru , Stöver Brigitte , Goecke Timm O. , Mundlos Stefan
Published: January 2004

Brachydactyly type C (BDC) is characterized by shortening of the middle phalanges of the index, middle, and little finger with hyperphalangy, usually of the index and middle finger. Heterozygous mutations of the cartilage derived morphogenetic protein‐1 (CDMP1) resulting in a loss of function have been reported in BDC. We here describe a large kindred with a semi‐dominant form of BDC and pronounced ulnar deviation of the second and third digits. In this family a novel homozygous missense mutation was identified (517A > G) changing methionine to valine at amino acid position 173. The mutation is located within a highly conserved seven amino acid region of the prodomain of CDMP1. Hand radiographs of heterozygous mutation carriers showed mild shortening of the metacarpals IV and V; a finding confirmed by the analysis of their metacarpophalangeal profiles (MCPPs). The mutation described here points toward an important function of the prodomain for the folding, secretion, and availability of biologically active CDMP1. © 2003 Wiley‐Liss, Inc.
Pre‐ and postnatal diagnosis of limb anomalies: A series of 107 cases
Authors: Holder‐Espinasse Muriel , Devisme Louise , Thomas Dominique , Boute Odile , Vaast Pascal , Fron Damien , Herbaux Bernard , Puech Francis , Manouvrier‐Hanu Sylvie
Published: January 2004

This is a 3‐year retrospective study of 107 cases presenting with limb anomalies detected either on prenatal ultrasound scan, or after birth. These limb malformations are developmental anomalies, and can be isolated, syndromic, or associated with multiple malformations. Cases were ascertained through the prenatal diagnosis center, the pediatrics department, and the feto‐pathology department. Several criteria were analyzed including sex ratio, prenatal diagnosis, karyotype, termination of pregnancies, clinical or pathological examination, pediatric or surgical and/or genetic assessment, and whether or not a diagnosis was made. Positional deformities and syndactyly were excluded. Limb anomalies were detected prenatally in 45% of the cases, and a diagnosis was made in 78%, including isolated, syndromic, or chromosomal anomalies. Sixty‐one per cent of the infants had follow‐up, either pediatric, surgical, or genetic. Prenatal multidisciplinary assessment is fundamental to assist with counseling, as is the post‐natal follow‐up of the infant. The diagnosis, if made, will obviously influence the information that will be given to the parents and the management of the malformation. If the pregnancy is terminated, feto‐pathological examination is essential to help make a diagnosis, and guide recurrence risks. We are currently undertaking a prospective study, and we will develop a protocol of investigations in the future, depending on the type of the malformation identified. © 2003 Wiley‐Liss, Inc.
Impact of BRCA1/2 testing and disclosure of a positive test result on women affected and unaffected with breast or ovarian cancer
Authors: van Roosmalen Mariëlle S. , Stalmeier P.F.M. , Verhoef L.C.G. , Hoekstra‐Weebers J.E.H.M. , Oosterwijk J.C. , Hoogerbrugge N. , Moog U. , van Daal W.A.J.
Published: January 2004

To evaluate the impact of BRCA1/2 testing and disclosure of a positive test result on women affected and unaffected with cancer. Longitudinal cohort study including women affected and unaffected with breast or ovarian cancer testing for a BRCA1/2 mutation. Data on well‐being (anxiety, depression, cancer related distress, general health), treatment choice, and decision making about cancer prevention were collected at baseline (1 week after blood sampling; affected n = 192, unaffected n = 176) and at follow‐up (2 weeks after disclosure of a positive test result; affected n = 23, unaffected n = 66). Women affected and unaffected with breast or ovarian cancer were compared using univariate statistics. Change over time was examined using repeated measures analysis of variance. With respect to well‐being, affected women scored worse at baseline. At follow‐up, both affected and unaffected women experienced a decline in well‐being, which tended to be stronger in affected women. Women diagnosed with cancer less than 1 year previously tended to report a worse well‐being than those diagnosed longer ago. With respect to treatment choice, more affected women intended to obtain prophylactic surgery and valued it higher at both time points. With respect to decision making, affected women had a lower preference for participation in decision making at baseline; no differences were found at follow‐up. At follow‐up, both affected and unaffected women showed an increase in strength of treatment preference and a decrease in decision uncertainty. Disclosure of a positive test result had a negative impact on well‐being. Affected women, especially those who have been recently diagnosed with cancer, experienced the worst well‐being and could benefit from psychosocial support. © 2003 Wiley‐Liss, Inc.
Fryns syndrome: A review of the phenotype and diagnostic guidelines
Authors: Slavotinek Anne M.
Published: January 2004

Fryns syndrome (FS) is the commonest autosomal recessive syndrome associated with congenital diaphragmatic hernia (CDH) and comprises CDH, pulmonary hypoplasia, craniofacial anomalies, distal limb hypoplasia, and internal malformations. Although there have been more than 50 case reports on probands with FS, the diagnostic guidelines were formulated from a review of eight patients and modifications to the guidelines have only once been suggested. Recently, several case reports have described new anomalies in FS and other papers have highlighted the variation in expressivity found in FS. This paper examines the medical literature on FS to define the phenotype and to review the diagnostic guidelines. We conclude that CDH with brachytelephalangy and/or nail hypoplasia is strongly suggestive of the diagnosis and that pulmonary hypoplasia, craniofacial dysmorphism, orofacial clefting, and polyhydramnios are sufficiently frequent to be diagnostically useful. Other distinctive malformations that are consistent with FS include ventricular dilatation or hydrocephalus, agenesis of the corpus callosum, neuronal or cerebellar heterotopias, abnormalities of the aorta, renal cysts, dilatation of the ureters, bicornuate uterus, renal dysplasia, proximal thumbs, and broad clavicles. © 2003 Wiley‐Liss, Inc.
Constitutional trisomy 8 mosaicism due to meiosis II non‐disjunction in a phenotypically normal woman with hematologic abnormalities
Authors: Baidas Said , Chen T‐J. , Kolev Valentin , Wong Lee‐Jun , Imholte Joel , Qin Naigeng , Meck Jeanne
Published: January 2004

Constitutional trisomy 8 mosaicism (CT8M) in liveborns is typically caused by mitotic non‐disjunction and exhibits wide phenotypic variability. By contrast, CT8M due to meiotic errors usually results in miscarriage. We describe a case of CT8M due to a paternal meiosis II non‐disjunction error. The patient, a 32‐year‐old woman, was phenotypically normal except for a history of recurrent aphthous ulcers since childhood and a 4‐year history of macrocytosis. The ulcers were refractory to steroids, but responded well to thalidomide. To the best of our knowledge, this is the first report of CT8M due to meiotic non‐disjunction in a phenotypically normal individual. © 2003 Wiley‐Liss, Inc.
Growth hormone deficiency (GHD): A new association in Peters' plus syndrome (PPS)
Authors: Lee Kuk‐Wha , Lee Phillip D. K.
Published: January 2004

We report a case of a girl with clinical features of Peters' Plus Syndrome (PPS) (association of anterior eye chamber defects; peculiar facies; cleft lip/palate; brachymelia; developmental delay; growth retardation) and documented growth hormone deficiency (height −3.5 SDS at chronological age 5 years 8 months; low growth factors; bone age delay; growth velocity 4.4 cm/year (<3rd centile); and peak growth hormone levels of 1.7 and 4.7 ng/ml by clonidine and insulin provocative testing, respectively). Treatment with recombinant human growth hormone (0.3 mg/kg/week) resulted in a dramatic increase in growth velocity, increasing the height from −3.5 to −1.5 SDS over 2.3 years of therapy, indicative of an excellent response. Growth retardation is a known association in PPS: a condition that includes other midline facial defects. This case supports a role for GHD in the pathogenesis of the short stature observed in these children; demonstrates the efficacy of GH treatment; and further reinforces the relationship of pituitary anomalies with common congenital defects. © 2003 Wiley‐Liss, Inc.
Retinoblastoma, pinealoma, and mild overgrowth in a boy with a deletion of RB1 and neighbor genes on chromosome 13q14
Authors: Skrypnyk Cristina , Bartsch Oliver
Published: January 2004

We report on a 10‐year‐old boy with a normal karyotype and a chromosome 13q14 deletion of the retinoblastoma gene (RB1) by fluorescence in situ hybridization (FISH). He showed subtle signs of overgrowth, including macrocephaly, hepatomegaly, and inguinal hernia. The boy also had cryptorchism and mild developmental delay. In his first months of life, variant Wiedemann–Beckwith syndrome was tentatively suspected and he was included in a careful tumor prevention program. At the age of 11 months, bifocal retinoblastoma of the left eye was diagnosed. Pinealoma was suspected at the age of 19 months and was removed by neurosurgery at the age of 29 months. At 4 years and 4 months, the deletion of the RB1 gene was suspected on clinical grounds and was diagnosed by FISH and molecular studies. At that time, he was a near‐normal healthy playful kindergarten child, height 107 cm (−0.3 SD), OFC 52.5 cm (+0.8 SD), developmental age 3–3.5 years. The combination of retinoblastoma, pinealoma, and deletion of the RB1 gene diagnosed by FISH has not been reported previously. The deletion spans at least 370–420 kb in size and is predicted to include proximal and distal neighbor genes. This report may assist in establishing the clinical signs of the contiguous gene syndrome at the RB1 locus on 13q14. © 2003 Wiley‐Liss, Inc.
Spinocerebellar ataxia type 2 (SCA2) presenting with ophthalmoplegia and developmental delay in infancy
Authors: Moretti Paolo , Blazo Maria , Garcia Leonardo , Armstrong Dawna , Lewis Richard Alan , Roa Benjamin , Scaglia Fernando
Published: January 2004

An 11‐year‐old boy was evaluated for progressive ataxia, cognitive deterioration, and ophthalmoplegia. The child initially presented with abnormal eye movements at the age of 2 months and was noted to have developmental delay at 6 months. At the age of 7 years, he developed ataxia and cognitive impairment, and subsequently manifested dysphagia and incontinence. The pertinent family history included gait difficulty in the paternal grandmother. At the age of 11, his general physical examination was normal. On neurological examination, he had bilateral external ophthalmoplegia, ataxic dysarthria, dysmetria and tremor in the upper extremities, and marked gait ataxia. An ophthalmological evaluation showed no evidence of pigmentary retinopathy. Brain MRI demonstrated cerebellar, brainstem, and cerebral atrophy. An ataxia panel showed 62 repeats in one allele of the SCA2 gene. Most cases of spinocerebellar ataxia type 2 (SCA2) present between 20 years and 40 years, and affected individuals typically have between 34 and 57 CAG repeats. Neonatal cases of SCA2 have been reported in individuals with over 200 CAG repeats. Childhood SCA2 has been reported previously in two patients but not described clinically. This case broadens the spectrum of the clinical features of infantile‐onset SCA2 and highlights the importance of considering this diagnosis in infants and children. © 2003 Wiley‐Liss, Inc.
Antenatal manifestations of Smith‐Lemli‐Opitz (RSH) syndrome: A retrospective survey of 30 cases
Authors: Goldenberg Alice , Wolf Claude , Chevy Françoise , Benachi Alexandra , Dumez Yves , Munnich Arnold , Cormier‐Daire Valérie
Published: January 2004

Smith‐Lemli‐Opitz (SLO) syndrome or RSH syndrome is an autosomal recessive multiple malformation, and mental retardation syndrome ascribed to 7‐dehydrocholesterol reductase deficiency, and usually diagnosed in the early postnatal period. Reviewing a series of 30 cases of SLO, we have investigated the variable antenatal expression of the disorder. Intrauterine growth retardation (IUGR) was the most frequent detectable trait (20/30). IUGR was either isolated (9/20) or associated with at least one other anomaly (11/20), including nuchal edema, renal, cardiac, cerebral malformations, genital anomalies, or polydactyly. In this last group, 3/11 presented with multiple malformations (≥3 anomalies). In 5/30 cases, isolated nuchal edema (3/30), and isolated cardiac (1/30) or renal malformations (1/30) were the only detectable anomalies. Ultrasound findings were considered normal in 5/30 cases and were abnormal in 25/30 cases (83%), but early detection of multiple malformations was rare (3/30, 10%). We suggest giving consideration to a more systematic sterol analysis when dealing with IUGR, especially when associated anomalies are detected. © 2003 Wiley‐Liss, Inc.
Variable clinical manifestation of homoplasmic G14459A mitochondrial DNA mutation
Authors: Gropman Andrea , Chen Tian‐Jian , Perng Cherng‐Lih , Krasnewich Donna , Chernoff Edith , Tifft Cynthia , Wong Lee‐Jun C.
Published: January 2004

Leber hereditary optic neuropathy (LHON)/pediatric onset dystonia is associated with a G to A transition at nucleotide position (np) 14459, within the mitochondrial DNA (mtDNA)‐encoded ND6 gene. This mutation has been reported in families presenting with LHON alone, LHON plus dystonia, or pediatric dystonia with typical age of onset less than 5 years. The mutation changes a moderately conserved alanine to a valine at amino acid residue 72, which is within the most evolutionarily conserved region of the ND6 protein. Pediatric onset disease is associated with basal ganglia dysfunction, spasticity, and encephalopathy. We report a family with G14459A mtDNA mutation and a broad spectrum of clinical manifestation. The proband was a 3‐year‐old girl with anarthria, dystonia, spasticity, and mild encephalopathy. MRI of the brain demonstrated bilateral, symmetric basal ganglia lucencies associated with cerebral and systemic lactic acidosis. Her maternal first cousin presented with a new onset limp and mild hemiparesis along with similar MRI findings with a much milder phenotype. Additional investigation of the family members with the mutation has revealed both asymptomatic and symptomatic individuals with variable clinical and laboratory features of mitochondrial disease. This study re‐emphasizes the heterogeneous clinical manifestation of homoplasmic G14459A mtDNA mutation even within the same family, and supports the hypothesis that nuclear genes may play a role in modifying the clinical expression of mitochondrial disease. Published 2003 Wiley‐Liss, Inc.
New 19 bp deletion polymorphism in intron‐1 of dihydrofolate reductase (DHFR): A risk factor for spina bifida acting in mothers during pregnancy?
Authors: Johnson William G. , Stenroos Edward S. , Spychala John R. , Chatkupt Sansnee , Ming Sue X. , Buyske Steven
Published: January 2004

Up to 72% of spina bifida cystica (SB) is preventable by maternal periconceptual folic acid supplementation. The C677T allele of the methylenetetrahydrofolate reductase (MTHFR) gene and some other functional polymorphisms are risk factors for SB in some populations. However, despite extensive study, the genetic risk factors for SB are incompletely understood. Polymorphic alleles that diminish bioavailability of reduced folate in the mother during pregnancy could contribute to SB in her fetus, acting in the mother as teratogenic alleles. We recently discovered a polymorphic 19 bp deletion allele (frequency 0.45) within intron‐1 of dihydrofolate reductase (DHFR) that is a good candidate for such a genetic factor. Since there is precedence for intron‐1 regulatory elements and the deletion allele removes a potential Sp1 transcription factor binding site, we hypothesized that the deletion allele could be functional and act in SB mothers to increase the risk of SB in her fetus. We found that homozygosity for this deletion allele was significantly more frequent in SB mothers, but not in SB fathers or patients, compared with controls and was associated with a significantly increased odds ratio (OR) (2.035) of being an SB mother compared with other genotypes. Genotype distribution obeyed the constraints of Hardy–Weinberg equilibrium in controls, SB patients and fathers, but not in SB mothers. If confirmed, these findings could lead to improved forms of folate supplementation for pregnancy. About half of dietary folates and all of folic acid supplements must be reduced by DHFR to be available for mother and fetus. Reduced folates could be preferable for supplements during pregnancy to prevent SB. © 2003 Wiley‐Liss, Inc.
Chemie in Mikrostrukturreaktoren
Authors: Jähnisch Klaus , Hessel Volker , Löwe Holger , Baerns Manfred
Published: January 2004

Mikrostrukturreaktoren haben in den letzten Jahren in der chemischen Verfahrenstechnik deutlich an Bedeutung gewonnen: Erste Firmen, die Prozessanlagen mit Mikrostrukturreaktoren anbieten, sind am Markt, eine Reihe von Instituten erforscht dieses Gebiet, Universitäten bieten Lehrveranstaltungen an, und einige verfahrenstechnisch orientierte Übersichtsartikel liegen bereits vor. Mikrostrukturierte Systeme sind besonders wertvoll für die Untersuchung stark exothermer schneller Reaktionen. Durch isotherme Betriebsweise lassen sich viele thermisch induzierte Nebenreaktionen zurückdrängen, was sicherheitstechnische Vorteile bei Reaktionen mit gefährlichen Reaktanten bringt. Obwohl viele organische Synthesen mit besseren Ergebnissen als in konventionellen Reaktoren durchgeführt wurden, ist der Mikrostrukturreaktor‐Technologie der große Durchbruch in der präparativen Chemie noch nicht gelungen. Aus diesem Grund unterstreicht dieser Aufsatz die Vorteile von Mikrostrukturreaktoren bei Flüssigphasen‐, Gasphasen‐ und Gas‐Flüssigphasen‐Reaktionen.
Titelbild: Chemie in Mikrostrukturreaktoren (Angew. Chem. 4/2004)
Authors: Jähnisch Klaus , Hessel Volker , Löwe Holger , Baerns Manfred
Published: January 2004

Mikrostrukturreaktoren wie der abgebildete SuperFocus‐Interdigital‐Mikromischer bieten eine Alternative zu konventionellen großtechnischen Prozessen. Strömungsmuster mit minimalen Schichtdicken führen zur Vergrößerung der Grenzflächen. So werden sehr kurze Mischzeiten erzielt, die hohe Durchsätze in den winzigen Reaktoren ermöglichen. K. Jähnisch, V. Hessel et al. vermitteln in ihrem Aufsatz auf S. 410 ff. das eindrucksvolle Potenzial dieses jungen Forschungsgebiets.
Organometallic Compounds for Nonlinear Optics—The Search for En‐light‐enment!
Authors: Long Nicholas J.
Published: January 2004

The importance of nonlinear optical phenomena has been known for some time, however, since the mid‐1980s, there has been an explosion of interest in the search for and development of non‐linear optical materials that possess commercial device applications. To date, the systems have been utilized in information processing, optical switching, optical frequency conversion, and telecommunications, and with the advancing development of optotechnology, burgeoning demands for suitable materials are becoming apparent. Of the many systems studied for example inorganic crystals and semiconductors, organic crystalline monomers, and long‐chain polymers with delocalized π electrons, no one species has proved to be all‐encompassing, with advantages for one application being negated by disadvantages for another. This is likely to remain the case for the foreseeable future with the criteria of the application governing the type of material used. However, chemists are gradually elucidating what actually governs second‐ and third‐order nonlinear activity and thereby, tailoring species to show greater effects. In recent years, organometallic compounds, through their unique characteristics such as diversity of metals, oxidation states, ligands, and geometries, have found success and brought a new dimension to the area. This review attempts, with critical appraisal, to bring the discussion of organometallic nonlinear optical systems up to date, as well as giving a brief but general introduction to the field of nonlinear optics.

For corrigendum see DOI:10.1002/anie.199508261
Toxins as Tools in Neurochemistry
Authors: Hucho Ferdinand
Published: January 2004

Neurotoxins have evolved as molecules targeted specifically against molecules with an important function in the nervous system. Because of their selectivity they have been used as probes for detecting and characterizing key proteins of the nerve cell. Ion channels involved in the propagation of the action potential, proteins of presynaptic neurotransmitter exocytosis, and most importantly, neurotransmitter receptors have been and are presently being analyzed, in some cases already at atomic level by a combination of the tools of neurotoxins, molecular biology, and patch clamp electrophysiology. In this review a selection of these toxins is presented, together with their targets in the nervous system. Special emphasis is given to the recent breakthroughs in our understanding of the mechanism of action of tetanus and botulinum toxins and to the neurotoxins ranging from the plant alkaloid strychnine to the peptide toxins from poisonous snakes, which were fundamental in elucidating ligand‐gated ion channels like the glycine and nicotinic acetylcholine receptors.
Barbituric Acid/2,4,6‐Triaminopyrimidine Aggregates in Water and Their Competitive Interaction with a Monolayer of Barbituric Acid Lipids at the Gas–Water Interface
Authors: Bohanon Thomas M. , Denzinger Steffen , Fink Ralf , Paulus Wolfgang , Ringsdorf Helmut , Weck Marcus
Published: January 2004

The first synthetic model for competitive exchange of an organic compound, specifically the exchange of triaminopyrimidine (TAP) between barbituric acid/TAP aggregates in water and highly ordered monolayers of a barbituric acid lipid, were studied by IR and UV/Vis spectroscopy. Similar competitive interaction are important in membranes and cell biology.
A Versatile Solid‐Phase Synthesis of N‐Linked Glycopeptides
Authors: Vetter Dirk , Tumelty David , Singh Sunil K. , Gallop Mark A.
Published: January 2004

A convergent synthesis not requiring sugar protecting groups yields N‐glycopeptides. The key step is the condensation of unprotected glycosylamines with resin‐bound peptides that have activated carboxyl groups in specified positions. Twenty‐three N‐linked glycopeptides such as 1 and 2 all derived from one peptide motif were obtained. This approach should facilitate generation of glycopeptide libraries.
The Stabilization of the Rb− Ion in Na16Rb7Sb7 = Na16(RbRb6)Sb7
Authors: von Schnering Hans Georg , Gil Raúl Hector Cardoso , Hönle Wolfgang , Burkhardt Armin , Krier Georges , Andersen Ole Krogh
Published: January 2004

An unusual electron distribution is shown by the ternary antimonide Na16Rb7Sb7, since only 21 of the 23 valence electrons of the alkali metal atoms are required for the formation of the Sb3− centers to be expected because of the semiconducting behavior. The remaining two electrons are localized in the region of a Rb center, which is located inside a Rb6 octahedron. The formulation of this center as Rb− is supported for example by the synthesis of the isostructural Na16Rb6ISb7 and by the results of quantum chemical calculations.
The Colors of C60 Solutions
Authors: Catalán Javier , Saiz José L. , Laynez José L. , Jagerovic Nadine , Elguero José
Published: January 2004

Differences in the absorption intensity in the spectral range between 400 and 500 nm, which the human eye perceives as changes in color, are the reason why solutions of C60 show different colors. The results of the experiments described rule out the formation of charge transfer complexes or of C60 aggregates.
Disulfide‐Reductase Inhibitors as Chemotherapeutic Agents: The Design of Drugs for Trypanosomiasis and Malaria
Authors: Schirmer R. Heiner , Müller Joachim G. , Krauth‐Siegel R. Luise
Published: January 2004

Viewed globally, parasitic diseases such as malaria and Chagas' cardiopathy pose an increasing threat to human health and welfare. Recognition of this problem and the challenge of synthesizing a quinine‐like antimalarial agent sparked off the development of the chemical industry about 100 years ago. Our contribution deals with aspects of drug design, a young branch of pharmaceutical chemistry. As drug targets the flavoenzyme, glutathione reductase, and the recently discovered parasite enzyme, trypanothione reductase, were chosen. Based on the knowledge of the structure of these molecules, the modeling of enzyme inhibitors as potential chemotherapeutic agents against parasites has become possible. In addition, biochemical and clinical observations are considered since chemical principles of biological evolution can serve as guidelines for the pharmaceutical chemists. The picture shows two erythrocytes destroyed by malaria parasites. In the center of the photograph a parasite is just leaving its host cell through the ruptured cell membrane. Its target could be a neighboring healthy erythrocyte.
Trace Analysis of the Radionuclides 90Sr and 89Sr in Environmental Samples I: Laser Mass Spectrometry
Authors: Lantzsch Jörg , Bushaw Bruce A. , Herrmann Günter , Kluge Heinz‐Jürgen , Monz Ludwin , Niess Sabine , Otten Ernst W. , Schwalbach Richard , Schwarz Martin , Stenner Judith , Trautmann Norbert , Walter Klaus , Wendt Klaus , Zimmer Klaus
Published: January 2004

Strontium‐90 is one of the most poisonous radionuclides. Its toxicity results from its long half‐life of 28.5 years and permanent deposition in the blood‐forming bone system. Strontium‐90 is formed in high yields during the nuclear fission of uranium‐235 and plutonium‐239. The classic analytical procedure for the determination of 90Sr, which relies on the β−‐radiation of the daughter nuclide yttrium‐90, necessitates the chemical removal of all accompanying nuclides. This method requires the Sr/Y ratio to be at equilibrium which takes about two to three weeks to achieve—far too long for the analysis of acute contaminations. Three communications deal with new procedures for ultra‐trace analysis using complex physical detection methods (resonance ionization and accelerator mass spectrometry) and high‐performance separation techniques (high‐performance ion chromatography, HPIC) are presented. In accordance with the strategies of the German Federal Ministry of the Environment, Nature Conservation, and Nuclear Safety, precision methods are described for the determination of the strontium‐90 content in aerosols. These techniques yield data for calculations of the spread of contaminants, which in turn yield results that can be verified in various samples with the aid of the novel fast detection method (HPIC with on‐line detectors). The three analytical procedures are set up in a modular manner and can therefore be utilized in variable combinations. They also indicate the high level of refinement achieved by modern ultra‐trace analyses.
Trace Analysis of the Radionuclides 90Sr and 89Sr in Environmental Samples III: Development of a Fast Analytical Method
Authors: Alfaro Juan , Apfel Thomas , Diercks Herbert , Knöchel Arndt , Gupta Rahul Sen , Tödter Klaus
Published: January 2004

Strontium‐90 is one of the most poisonous radionuclides. Its toxicity results from its long half‐life of 28.5 years and permanent deposition in the blood‐forming bone system. Strontium‐90 is formed in high yields during the nuclear fission of uranium‐235 and plutonium‐239. The classic analytical procedure for the determination of 90Sr, which relies on the β−‐radiation of the daughter nuclide yttrium‐90, necessitates the chemical removal of all accompanying nuclides. This method requires the Sr/Y ratio to be at equilibrium which takes about two to three weeks to achieve—far too long for the analysis of acute contaminations. Three communications deal with new procedures for ultra‐trace analysis using complex physical detection methods (resonance ionization and accelerator mass spectrometry) and high‐performance separation techniques (high‐performance ion chromatography, HPIC) are presented. In accordance with the strategies of the German Federal Ministry of the Environment, Nature Conservation, and Nuclear Safety, precision methods are described for the determination of the strontium‐90 content in aerosols. These techniques yield data for calculations of the spread of contaminants, which in turn yield results that can be verified in various samples with the aid of the novel fast detection method (HPIC with on‐line detectors). The three analytical procedures are set up in a modular manner and can therefore be utilized in variable combinations. They also indicate the high level of refinement achieved by modern ultra‐trace analyses.
Investigation of Self‐Assembled Supramolecular Species in Solution by IL‐ESMS, a New Mass Spectrometric Technique
Authors: Russell Keith C. , Leize Emmanuelle , Van Dorsselaer Alain , Lehn Jean‐Marie
Published: January 2004

Discrete neutral assemblies in solution can be studied with the analytical method described here. A prerequisite is that one of the components contains an ion‐complexing site, for example a crown ether unit. When alkali metal ions are added, charged assemblies form, which can be examined by electrospray mass spectrometry (ESMS) without disruption of their hydrogen bonds. IL in the title stands for ion labeling.
Gas‐Phase Activation of Fluorocarbons by “Bare” and Coordinated Praseodymium Cations
Authors: Heinemann Christoph , Goldberg Norman , Tornieporth‐Oetting Inis C. , Klapötke Thomas M. , Schwarz Helmut
Published: January 2004

Rather than CH or CC bonds, Pr+ activates CF bonds in the gas phase in a variety of aliphatic and aromatic fluorocarbons; PrF+ and PrO+ react analogously. This first general example of preferential CF bond activation in the gas phase allows interesting conclusions to be drawn regarding the importance of 4f electrons for the reactivity of isolated lanthanide species. The existence of neutral PrF and PrF2 in the gas phase was also proven by neutralization–reionization mass spectrometry (NRMS).
Atom Economy—A Challenge for Organic Synthesis: Homogeneous Catalysis Leads the Way
Authors: Trost Barry M.
Published: January 2004

Enhancing the efficiency of the synthesis of complex organic products constitutes one of the most exciting challenges to the synthetic chemist. Increasing the catalogue of reactions that are simple additions or that minimize waste production is the necessary first step. Transition metal complexes, which can be tunable both electronically and sterically by varying the metal and/or ligands, are a focal point for such invention. Except for catalytic hydrogenation, such methods have been rare in complex synthesis and virtually unknown for CC bond formation until the advent of cross‐coupling reactions. These complexes may orchestrate a variety of CC bond‐forming processes, important for creation of the basic skeleton of the organic structure. Their ability to insert into CH bonds primes a number of different types of additions to relatively nonpolar π‐electron systems. Besides imparting selectivity, they make feasible reactions that uncatalyzed were previously unknown. The ability of these complexes to preorganize π‐electron systems serves as the basis both of simple additions usually accompanied by subsequent hydrogen shifts and of cycloadditions. The ability to generate “reactive” intermediates under mild conditions also provides prospects for new types of CC bond‐forming reactions. While the examples reveal a diverse array of successes, the opportunities for new invention are vast and largely untapped.
Digitalis Research in Berlin–Buch—Retrospective and Perspective Views
Authors: Repke Kurt R. H. , Megges Rudolf , Weiland Jürgen , Schön Rudolf
Published: January 2004

“The following remarks consist partially of matter of fact, and partially of opinion. The former will be permanent; the latter must vary with the detection of error, or the improvement of knowledge. I hazard them with diffidence, and hope they will be examined with candour.” These declarations, which stem from the famous book “An Account of the Foxglove and some of its Medical Uses” by physician William Withering in 1785 in which he introduced preparations from digitalis leaves in the therapy of dropsy (cardiac failure), are cited here by the senior author because of his awareness of the difficulties in presenting a balanced report on his life‐long research project on the further development of digitalis. His decision to devote himself to digitalis research originated at the bedside, when as a physician he experienced the grim final stages of cardiac failure in which no real help for the patients is possible. Unfortunately, his research project did not fit into the research program decreed by the Ministry of Science of the German Democratic Republic, so that he was ordered to stop the digitalis project in favor of biomembrane studies. Fortunately, he got round the ban simply by labeling the digitalis‐like acting steroids as probes for the cell membrane‐located Na+/K+‐transporting ATPase which he had just recognized as the digitalis target (receptor) enzyme. These and other ventures by the authors are collated here for the first time. The aim of this review is to foster straightforward research for solving a major challenge: the development of steroidal drugs for the prevention and cure of cardiac failure.
Electron Transfer through DNA: Site‐Specific Modification of Duplex DNA with Ruthenium Donors and Acceptors
Authors: Meade Thomas J. , Kayyem Jon F.
Published: January 2004

The rate of the electron transfer between two ruthenium centersat the ends of an octanucleotide duplex (metal‐to‐metal distance = 21 Å) was determined to be 1.6(4) × 106s−1. By using automated DNA synthesis techniques, modified oligonucleotides were prepared with a protected phosphoroamidite of 2′‐amino‐2′‐deoxyuridine. The NH2‐modified oligonucleotides were hybridized with complementary DNA sequences to protect nucleotide bases, and then treated with ruthenium complexes. In this way the ruthenium complex was bound only to the free NH2group.
Structure and Bonding of Transition Metal Dihydrogen Complexes [M(CO)5(H2)] (M = Cr, Mo, W)
Authors: Dapprich Stefan , Frenking Gernot
Published: January 2004

Important intermediates in catalytic hydrogenation, η2‐dihydrogen complexes are also appealing subjects for theoretical studies. The MH2binding enthalpies for the complexes [M(CO)5(H2)] (M = Cr, Mo, W) were calculated at the CCSD(T)/MP2 level as 15.9 (M = Cr), 12.8 (M = Mo), and 16.3 kcal mol−1(M = W). Charge decomposition analysis suggests that H2is a significant σ donor and a moderate π acceptor. The topological analysis of the electron density distribution indicates a cyclic structure for the MH2moiety.
Probing Protein Structure and Function with an Expanded Genetic Code
Authors: Cornish Virginia W. , Mendel David , Schultz Peter G.
Published: January 2004

A general biosynthetic method has been developed which makes it possible to site‐specifically incorporate unnatural amino acids with novel properties into proteins. In this approach the codon encoding the amino acid of interest is replaced with the “blank” nonsense codon UAG by oligonucleotide‐directed mutagenesis. A suppressor tRNA that recognizes this codon is generated by run‐off transcription and then chemically aminoacylated with the desired unnatural amino acid. Addition of the mutagenized gene and the aminoacylated suppressor tRNA to an in vitro extract capable of supporting protein biosynthesis generates a mutant protein containing the unnatural amino acid at the specified position. This methodology has recently been used to study the stability, specificity, and catalytic properties of a number of proteins. In these studies amino acids and analogues possessing altered hydrogen‐bonding, electronic, and steric properties and unique backbone conformations have all been site‐specifically incorporated into proteins. In addition, photoactivatable amino acids, isotopically labeled amino acids, and amino acids bearing biophysical probes have been inserted site‐specifically. This chemistry increases our ability to carry out detailed physical organic studies on this important class of macromolecules.
Preparative Solid‐State Chemistry with High‐Power CO2 Lasers
Authors: Möhr Sönke , Möller‐Buschbaum Hanskarl
Published: January 2004

The establishment of solid state chemistry as an independent field, which also has had a stimulating effect on material sciences, is a consequence of the experimental skill of chemists. The development of new methods led to an abundance of new compounds, the characteristic properties of which are linked with the solid state. The reaction temperature plays an important role in the synthesis of solid compounds; therefore, it is not surprising that a large number of the newly developed experimental techniques involve methods which can produce high temperatures on the openended temperature scale. Since the development of the CO2 laser, the solidstate chemist has an excellent heat source available, and with the power available today the range of high temperatures possible has been extended considerably. A way is now open for producing metastable, “entropy‐supported” high‐temperature compounds and substances with anomalous oxidation states and with macroscopic defects.
Direct On‐Line Coupling of Capillary Electrophoresis and 1H NMR Spectroscopy
Authors: Albert Klaus
Published: January 2004

Nanoliter NMR probes enabled the direct coupling of capillary electrophoresis with 1H NMR spectroscopy to be realized for the first time. How effective this combined technique will be and whether analytical problems can be solved with it depends on the further development of the coil design, since the resolution achieved to date is too low.
Coupling of Endothermic Thermal Cracking with Exothermic Oxidative Dehydrogenation of Ethane to Ethylene Using a Diluted SrO/La2O3 Catalyst
Authors: Choudhary Vasant R. , Uphade Balu S. , Mulla Shafeek A. R.
Published: January 2004

The energy‐efficient and safe conversion of ethane into ethylene is possible by simultaneous exothermic oxidative dehydrogenation and endothermic cracking of ethane in the presence of steam and limited amounts of O2, by using the thermally and hydrothermally stable supported catalyst SrO/La2O3/SA 5205 diluted with an inert support. Because the exothermic and endothermic reactions are coupled, this process requires only very little or no applied energy.
31P CP/MAS NMR Spectroscopy of Transition Metal Phosphane Complexes: “J‐Recoupling” between Chemically Equivalent 31P Nuclei in Polycrystalline Compounds of the Type trans‐[(PR3)2MX2], MPd, Pt
Authors: Klaus Elke , Sebald Angelika
Published: January 2004

Minor modification—large effect: Replacement of Et3P by nBu3P in otherwise homologous complexes of the type 1 can dramatically change the solid‐state NMR properties. The reason is that–although both compounds show 31PA2 spin systems in solution–only in one case are the 31P nuclei also magnetically equivalent in the solid state. Therefore a reliable interpretation of the high‐resolution solid‐state 31P NMR spectra must take into consideration the orientation‐dependent interactions within the 31P spin pair.
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Carbon—Hydrogen Bonds of DNA Sugar Units as Targets for Chemical Nucleases and Drugs
Authors: Pratviel Geneviève , Bernadou Jean , Meunier Bernard
Published: January 2004

This review article focuses on the molecular aspects of DNA cleavage by synthetic chemical nucleases (transition metal complexes endowed with redox properties and DNA affinity) and natural drugs (cytotoxic agents such as bleomycins or enediynes). Unlike deoxyribonucleases, which catalyze the nucleophilic attack of water on the phosphorus atom of a particular phosphodiester entity, these nonhydrolytic DNA‐cleavers are able to oxidize the sugar units, generally by hydrogen atom abstraction. Examples of oxidative attack on each of the five different CH bonds of deoxyribose are known, depending on the nature, structure, type of activation, or mode of DNA interaction of the DNA‐cleaver. Further evolution at the site of the initial lesion leads to the release of bases, oxidized deoxyribose units, or oxidized sugar fragments appended to the base or the terminal phosphate. In most cases the loss of a part (at least) of a nucleoside, with the concomitant loss of one base information, primarily induces the cleavage of the DNA strand. For both types of DNA cleavage reagents studied within the two last decades, the modes of activation and DNA binding are presented, as well as the details on the mechanism of deoxyribose oxidative degration. Because of the need for highly efficient and highly specific reagents, the development of new artificial and selective DNA cleavers, supported by an improved knowledge of these different mechanisms of DNA cleavage, is to‐day a challenging area in the rational design of antitumoral or antiviral agents, as well as in the field of molecular biology.
Coordination of CO to the Alkaline Earth Metallocene [(Me5C5)2Ca]
Authors: Selg Peter , Brintzinger Hans H. , Andersen Richard A. , Horváth István T.
Published: January 2004

The exothermic formation of a Ca–CO complex [Eq.(a), ΔHo = −25 kJ mol−1] confirms that CO can bind to a metal center without π back donation from filled d orbitals. In its spectroscopic properties, the calcocene–carbonyl complex resembles “nonclassical” noble metal carbonyl complexes. Cp* = η5‐C5Me5.
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Reaction of a Vanadium(III) Amide with H2: Isolation and Characterization of a Polynuclear Mixed‐Valence Polyhydrido–Nitrido Complex
Authors: Berno Pietro , Gambarotta Sandro
Published: January 2004

Complex 2 is formed by two discrete ions which originate during hydrogenolysis of 1 according to Equation (a). The cation is dinuclear with three bridging hydrido ligands. The mixed‐valent anion of 2 is also dinuclear and contains two bridging nitrido moieties, which cannot be the product of the hydrogenolysis of NSi bonds since silanes are not formed in the reaction.
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Model Reactions for Photosynthesis—Photoinduced Charge and Energy Transfer between Covalently Linked Porphyrin and Quinone Units
Authors: Kurreck Harry , Huber Martina
Published: January 2004

Photosynthesis is one of the fascinating fields of current interdisciplinary research. It seems miraculous that nature, in the process of evolution, has managed to bring about the process of photosynthesis. The first step involves a charge separation at the reaction centers, which proceeds with 100% quantum yield from the photoexcited singlet state of the bacteriochlorophyll donor, despite the fact that the wasteful deactivation of the electron into the ground state should be highly favored. Biomimetic model compounds (that is, those which resemble the pigments nature has developed) have been constructed from porphyrins and quinones. These model systems have allowed the study of the factors contributing to the highly efficient charge separation. This report focuses on recent developments in the study of electron transfer in porphyrinoquinones. Some of the results of these investigations may not be not fully understood and are often the subject of controversial discussions.
Anticoagulatory Substances of Bloodsucking Animals: From Hirudin to Hirudin Mimetics
Authors: Dodt Johannes
Published: January 2004

Bloodsucking animals contain substances in their saliva that specifically interfere with the blood clotting system. These substances are mainly low molecular weight proteins with a molecular mass of between 4 and 50 kDa. Some have become accessible in large quantities with the help of genetic engineering, and as a result their structures and structure—activity relationships have been studied and clinically tested. In the light of what is known about the mode of action of these natural products at the molecular level, new compounds with possible therapeutic effect can be derived. In the last ten years this approach has been tested with the proteinase inhibitor hirudin, obtained from medicinal leeches, and with the thrombin/hirudin complex. The serine protease thrombin plays a central role in the complex pathway of the blood clotting process and its pathophysiological effect finally results in thrombosis. The selectivity of the formation of complexes from hirudin and thrombin lies in the bivalent interaction of the inhibitor with the active site of the enzyme as well as with a substrate recognition site outside of the active site, the so‐called fibrin‐(ogen) binding site (FBS). The knowledge of this mode of action enabled the synthesis of bifunctional thrombin inhibitors based on hirudin peptides. Hirudin and hirudin mimetics in vivo have been shown to be highly potent anticoagulants for the treatment of arterial and venous thrombosis.
Control of Ion–Molecule Reactions in the Gas Phase
Authors: Gericke Karl‐Heinz
Published: January 2004

Excitation of a particular stretching vibration in the reagent ion NH influences the course of its reaction with ND3. The extent of charge transfer (a), proton transfer (b), and deuterium abstraction (c) depends on how the unbrella mode and the symmetrical breathing mode are excited. Thanks to the work of Zare et al. discussed here, the goal of controlling the reaction channels of complex molecules is a little closer.
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Synthesis, Structural Investigation, and Ligand Properties of Isocyanoacetonitrile
Authors: Lentz Dieter , Scharn Dirk , Willemsen Stefan , Buschmann Jürgen , Luger Peter , Perpetuo Genivaldo
Published: January 2004

An NC and a CN group bonded to CH2 describes the structure of the title compound 1. The unstable compound 1 was obtained analytically pure for the first time and characterized spectroscopically. The X‐ray crystal structure analysis enables a direct comparison of the isomeric nitrile and isocyanide functions. First investigations on complexes of 1 show that low‐valent metal complex fragments coordinate preferably to the isocyanide group.
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