bluuebunny/crossref_metadata_2025 huggingface dataset:
“We Kept Our Promises”: An oral history of Harry Shwachman, M.D.
Authors: Fanos Joanna H.
Published: January 2008

Harry Shwachman, M.D., was Chief of the Division of Clinical Nutrition at Children's Hospital, Boston, which eventually became the largest Cystic Fibrosis (CF) center in the world. For over four decades he pioneered understanding of the disease and developed a program of diagnosis and treatment that dramatically extended the lives of children affected with CF. During his own childhood, he developed bilateral pneumonia and nearly died. He received a BS from M.I.T in 1932, and an MD from Johns Hopkins in 1936. He completed his internship and residency at Johns Hopkins and Children's Hospital, Boston (1937–1941). In 1947 he returned from Army service to Boston where he resumed his medical practice and research. Dr. Shwachman discovered a less invasive screening procedure for CF than the intubation technique used previously. In the late 1940s he and his colleagues identified pulmonary involvement to be the primary manifestation of CF. He was instrumental in establishing the autosomal recessive genetic pattern of CF [Allen et al., 1956]. He introduced new treatment methods that changed the management of CF, including the use of antibiotics in 1948, a new pancreatic enzyme replacement, and chest physical therapy. In 1954 Shwachman developed the first reproducible sweat test at Children's Hospital, Boston, and in 1955 he helped establish the Cystic Fibrosis Foundation. He authored over 250 publications, trained generations of researchers, and was a dedicated clinician, legendary for his devotion to his patients and their families. In addition, he was an accomplished violinist and founding member of the Newton Symphony Orchestra. He and Irene, his wife of 42 years, had three children: Elizabeth, Joan, and Alan, and at the time of interview, three grandchildren. This autobiographical vignette is based on excerpts from an interview I conducted of Dr. Shwachman and his wife in their home in Boston in 1984, 2 years prior to his death. © 2008 Wiley‐Liss, Inc.
Expanding the phenotype of mosaic trisomy 20
Authors: Willis Mary J.H. , Bird Lynne M. , Dell'Aquilla Marie , Jones Marilyn C.
Published: January 2008

Mosaic trisomy 20 is one of the more common cytogenetic abnormalities found on amniocentesis or chorionic villus sampling. Studies have shown that outcome is normal in 90–93% of prenatally diagnosed cases. There are however, reports in the literature of children with mosaic trisomy 20 described as having an assortment of dysmorphic features and varying levels of developmental delay. Unfortunately, the literature has not defined a specific phenotype for this entity. Here we report on three patients with mosaic trisomy 20, two of whom were identified prenatally. Over a number of years of follow‐up it has become apparent that there are some striking similarities among the three. Comparison between our patients and the literature cases indicates a more consistent phenotype than has previously been suggested. Recurring features include; spinal abnormalities (including spinal stenosis, vertebral fusion, and kyphosis), hypotonia, lifelong constipation, sloped shoulders, and significant learning disabilities despite normal intelligence. These findings may be overlooked on routine history and physical exam or assumed to be standard pediatric problems. It is not our intention to suggest that there is a distinctive face for this entity but to suggest that a subtle phenotype does exist. We have attempted to identify a set of findings for which any child diagnosed with mosaic trisomy 20 should be assessed or followed even in the presence of an apparently normal physical exam at birth. © 2008 Wiley‐Liss, Inc.
Chromosome deletions in 13q33–34: Report of four patients and review of the literature
Authors: Walczak‐Sztulpa Joanna , Wisniewska Marzena , Latos‐Bielenska Anna , Linné Maja , Kelbova Christina , Belitz Britta , Pfeiffer Lutz , Kalscheuer Vera , Erdogan Fikret , Kuss Andreas W. , Ropers Hans‐Hilger , Ullmann Reinhard , Tzschach Andreas
Published: January 2008

Deletions of chromosome bands 13q33–34 are rare. Patients with such deletions have mental retardation, microcephaly, and distinct facial features. Male patients frequently also have genital malformations. We report on four patients with three overlapping deletions of 13q33–34 that have been characterized by tiling‐path array‐CGH. Patient 1 had mental retardation and microcephaly with an interstitial 4.7 Mb deletion and a translocation t(12;13)(q13.3;q32.3). His mother (Patient 2), who also had mental retardation and microcephaly, carried the identical chromosome aberration. Patient 3 was a girl with a de novo insertion ins(7;13)(p15.1;q22q31) and interstitial 4.5 Mb deletion in 13q33–34. She had mental retardation and microcephaly. Patient 4 was a newborn boy with severe genital malformation (penoscrotal transposition and hypospadias) and microcephaly. He had a de novo ring chromosome 13 lacking the terminal 9.3 Mb of 13q. Karyotype–phenotype comparisons of these and eight previously published del13q33–34 patients suggest EFNB2 as a candidate gene for genital malformations in males. Molecular cytogenetic definition of a common deleted region in all patients suggests ARHGEF7 as a candidate gene for mental retardation and microcephaly. © 2008 Wiley‐Liss, Inc.
DLX3 c.561_562delCT mutation causes attenuated phenotype of tricho‐dento‐osseous syndrome
Authors: Wright J. Timothy , Hong Sung P. , Simmons Darrin , Daly Bill , Uebelhart Daniel , Luder Hans U.
Published: January 2008

The distal‐less homeobox gene DLX3 is expressed in a variety of tissues including placenta, skin, hair, teeth, and bone. Mutation of DLX3 (c.571_574delGGGG) causes the tricho‐dento‐osseous syndrome (TDO), characterized by abnormal hair, teeth, and bone. Evaluation of a kindred segregating the DLX3 c.561_562delCT mutation revealed distinct changes in the hair, teeth, and bones as has been observed with the DLX3 c.571_574delGGGG mutation. Previously, the DLX3 c.561_562delCT mutation was associated with autosomal dominant amelogenesis imperfecta with taurodontism. The present study shows that the DLX3 c.560_561delCT mutation causes an attenuated TDO phenotype with less severe hair, tooth, and bone manifestations compared with individuals having the DLX3 c.571_574delGGGG mutation. Careful phenotyping of individuals with allelic DLX3 mutations reveals marked differences in phenotypic severity indicating that the carboxy‐terminus of the DLX3 protein is critical in determining its function during development in these different tissues. © 2008 Wiley‐Liss, Inc.
Severe neonatal non‐dystrophic myotonia secondary to a novel mutation of the voltage‐gated sodium channel (SCN4A) gene
Authors: Gay Sébastien , Dupuis Delphine , Faivre Laurence , Masurel‐Paulet Alice , Labenne Marc , Colombani Marina , Soichot Pierre , Huet Frédéric , Hainque Bernard , Sternberg Damien , Fontaine Bertrand , Gouyon Jean‐Bernard , Thauvin‐Robinet Christel
Published: January 2008

We report on a patient with a severe, rare neonatal form of non‐dystrophic myotonia. The patient presented with facial dysmorphism, muscle hypertrophy, severe constipation, psychomotor delay, and frequent cold‐induced episodes of myotonia and muscle weakness leading to severe hypoxia and loss of consciousness. Muscle biopsy was non‐specific and electromyography revealed intense generalized myotonia. The myotonic episodes improved after introducing oral mexiletine and maintaining room temperature at 28°C. The patient died at 20 months of age following a bronchopulmonary infection. A previously undescribed de novo heterozygous c.3891C > A change, which predicts p.N1297K in the SCN4A gene. Mutations within the voltage‐gated sodium channel alpha‐subunit gene (SCN4A) have been described in association with several phenotypes including paramyotonia congenita, hyperkalemic or hypokalemic periodic paralysis, and potassium‐aggravated myotonias. The cold‐sensitive episodes of stiffness followed by weakness suggested the diagnosis of channelopathy in our patient. However, her neonatal onset, the triggering of severe episodes by exposure to modest decreases in temperature, involvement of respiratory muscles with prolonged apnea, early‐onset muscle hypertrophy, psychomotor retardation, and fatal outcome are evocative of a distinct clinical subtype. Our observation expands the phenotypic spectrum of sodium channelopathies. © 2008 Wiley‐Liss, Inc.
Paternal deletion 6q24.3: A new congenital anomaly syndrome associated with intrauterine growth failure, early developmental delay and characteristic facial appearance
Authors: Nowaczyk Małgorzata J.M. , Carter Melissa T. , Xu Jie , Huggins Marlene , Raca Gordana , Das Soma , Martin Christa Lese , Schwartz Stuart , Rosenfield Robert , Waggoner Darrel J.
Published: January 2008

Deletions of the long arm of chromosome 6 are relatively uncommon and to date minimal genotype–phenotype correlations have been observed. We report on three unrelated patients with de novo paternal interstitial deletions of 6q24.3. FISH mapping was used to delineate the minimal region of overlap between these three patients. Although all three patients had different size deletions and different breakpoints, two of the patients shared a 2.5 Mb region of overlap and strikingly similar facial features including a triangular face, frontal bossing with metopic prominence, short and upward‐slanting palpebral fissures, asymmetry of upper eyelids, hooded eyelids, shallow orbits, prominent inferior orbital crease, wide mouth, and long and flat philtrum. They also had redundant skin, joint laxity, a small thorax, and early developmental delay. The smallest region of overlap between all three patients was a region of deletion less than 1 Mb; all had a history of IUGR and postnatal short stature without overt radiologic skeletal anomalies. The dysmorphic features, early developmental and growth delay may be due to the hemizygous state for one of the genes in the deleted region of two of the patients or to a long range effect of the deletion on expression of other genes. In addition, since imprinted genes have been reported in this region, paternal deletion of an imprinted gene in all three patients may contribute to the growth phenotype. We propose that this is a new congenital malformation syndrome associated with a paternal deletion of 6q24.3. © 2008 Wiley‐Liss, Inc.
Empirical data about women's attitudes towards a hypothetical pediatric biobank
Authors: Neidich Alon B. , Joseph Josh W. , Ober Carole , Ross Lainie Friedman
Published: January 2008

Researchers at the University of Chicago sought institutional review board (IRB) approval to establish both an obstetrical biobank (Chicago Lying‐in Pregnancy Program [CLIPP]) and a pediatric biobank (KidsGene). Before KidsGene was approved, the IRB requested additional ethical review. The research ethics consultation service noted that no empirical data existed about parental attitudes towards this type of project. Postpartum women 18 years or older who delivered at the University of Chicago Hospitals and had live infants on the General Care Nursery service were approached about participating in a survey about the CLIPP biobank and about a hypothetical pediatric biobank. Two hundred thirty‐nine women were consented and completed most or all of the survey. Eighty‐two percent self‐classified as Black and seven percent were Caucasians. Caucasians were the most willing to enroll their children hypothetically into a pediatric biobank with non‐Black minorities being the most uncertain about what they would do. Almost half of the women thought that the research had the main goal of advancing science although a similar number expressed the belief that the research had the main goal of helping their individual child. Women supported use of the samples for a wide array of pediatric conditions. Comprehension of research practices, trust in medical researchers, and a belief that the research findings would be used fairly correlated with enrollment. Our survey found that most women support biobank development for research purposes. Most respondents expressed optimism that the results will yield significant benefits and that the benefits will be distributed fairly. © 2008 Wiley‐Liss, Inc.
A unique case of fibrodysplasia ossificans progressiva with an ACVR1 mutation, G356D, other than the common mutation (R206H)
Authors: Furuya Hirokazu , Ikezoe Koji , Wang Lixiang , Ohyagi Yasumasa , Motomura Kyoko , Fujii Naoki , Kira Jun‐ichi , Fukumaki Yasuyuki
Published: January 2008

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant congenital disease characterized by progressive heterotopic endochondral osteogenesis with great‐toe malformations. A 617G > A (R206H) mutation of the activin A type 1 receptor gene (ACVR1) has been found in all previously reported patients with FOP. Thus, this is one of the most specific of all disease‐associated mutations. We report here on a 62‐year‐old man with slowly progressive FOP and a novel mutation in ACVR1. He developed difficulty in moving his shoulder since age 10 years due to contraction of the shoulder joint. The symptoms progressed slowly, and he could not walk at age 36 years and was bedridden at 55 years. He also showed rigid spine, baldness, sensorineural hearing loss, and hypodactyly accompanied by abnormal ectopic ossification. Analysis of ACVR1 and its cDNA revealed that the patient is heterozygous for a mutation, 1067G > A (G356D). Typing of SNPs located in the ∼0.5‐Mb region spanning ACVR1 and its neighbor genes suggested that 1067G > A is a de novo mutation. These results give a clue to better understanding of FOP as well as of the mild clinical symptoms in the patient. © 2008 Wiley‐Liss, Inc.
Carotid artery dissection in an adult with the Simpson–Golabi–Behmel syndrome
Authors: Pénisson‐Besnier Isabelle , Lebouvier Thibaud , Moizard Marie‐Pierre , Ferré Marc , Barth Magalie , Marc Guillaume , Raynaud Martine , Bonneau Dominique
Published: January 2008

We report on the case of a 44‐year‐old man affected with the Simpson–Golabi–Behmel syndrome (SGBS) (OMIM 312870) presenting with ischemic stroke due to a dissection of the right internal carotid. Molecular genetic analysis revealed the p.Gly556Arg mutation in exon 8 of the gene encoding glypican 3 (GPC3). This is the second case of a GPC3 missense mutation to be reported. The only risk factor found in this patient was carotid redundancy, a deformation that is significantly associated with spontaneous carotid dissection. The natural history of SGBS in adults is poorly known, and this case raises the question of a possible vascular risk associated with the disease. © 2008 Wiley‐Liss, Inc.
Failure to replicate effect of kibra on human memory in two large cohorts of European origin
Authors: Need Anna C. , Attix Deborah K. , McEvoy Jill M. , Cirulli Elizabeth T. , Linney Kristen N. , Wagoner Ana Patricia , Gumbs Curtis E. , Giegling Ina , Möller Hans‐Jürgen , Francks Clyde , Muglia Pierandrea , Roses Allen , Gibson Greg , Weale Mike E. , Rujescu Dan , Goldstein David B.
Published: January 2008

It was recently suggested that the Kibra polymorphism rs17070145 has a strong effect on multiple episodic memory tasks in humans. We attempted to replicate this using two cohorts of European genetic origin (n = 319 and n = 365). We found no association with either the original SNP or a set of tagging SNPs in the Kibra gene with multiple verbal memory tasks, including one that was an exact replication (Auditory Verbal Learning Task, AVLT). These results suggest that Kibra does not have a strong and general effect on human memory. © 2008 Wiley‐Liss, Inc.
Initial association of NR2E1 with bipolar disorder and identification of candidate mutations in bipolar disorder, schizophrenia, and aggression through resequencing
Authors: Kumar Ravinesh A. , McGhee Kevin A. , Leach Stephen , Bonaguro Russell , Maclean Alan , Aguirre‐Hernandez Rosalia , Abrahams Brett S. , Coccaro Emil F. , Hodgins Sheilagh , Turecki Gustavo , Condon Anne , Muir Walter J. , Brooks‐Wilson Angela R. , Blackwood Douglas H. , Simpson Elizabeth M.
Published: January 2008

Nuclear receptor 2E1 gene (NR2E1) resides within a 6q21‐22 locus for bipolar disorder and schizophrenia. Mice deleted for Nr2e1 show altered neurogenesis, cortical and limbic abnormalities, aggression, hyperexcitability, and cognitive impairment. NR2E1 is therefore a positional and functional candidate for involvement in mental illness. We performed association analyses in 394 patients with bipolar disorder, 396 with schizophrenia, and 479 controls using six common markers and haplotypes. We also performed a comprehensive mutation screen of NR2E1, resequencing its entire coding region, complete 5′ and 3′ untranslated regions, consensus splice‐sites, and evolutionarily conserved regions in 126 humans with bipolar disorder, schizophrenia, or aggressive disorders. NR2E1 was associated with bipolar disorder I and II [odds ratio (OR = 0.77, P = 0.013), bipolar disorder I (OR = 0.77, P = 0.015), bipolar disorder in females (OR = 0.72, P = 0.009), and with age at onset ≤25 years (OR = 0.67, P = 0.006)], all of which remained significant after correcting for multiple comparisons. We identified eight novel candidate mutations that were absent in 325 controls; four of these were predicted to alter known neural transcription factor binding sites. Analyses of NR2E1 mRNA in human brain revealed forebrain‐specific transcription. The data presented support the hypothesis that genetic variation at NR2E1 may be associated with susceptibility to brain‐behavior disorders. © 2008 Wiley‐Liss, Inc.
Nanoclay plating of cellulosic fiber surfaces
Authors: Lindström Tom , Banke Karl , Larsson Tomas , Glad‐Nordmark Gunborg , Boldizar Antal
Published: January 2008

A basic problem in making cellulose‐reinforced composites is achieving a dispersion of cellulosic fibers in an often olephinic polymer matrix. Drying cellulosic fibers results in the formation of fiber flocs/nodules because of their strong interfiber bonding, and this makes the hydrophilic cellulosic fibers difficult to disperse in a hydrophobic matrix material. One common approach to alleviate floc formation is to adsorb cationic surfactant onto anionically charged cellulose, which reduces the interfiber bonding, decreases floc formation and gives better compatibility with the matrix. In this report, a different approach is taken, namely to adsorb nanoclays onto the cellulosic fibers, and thereby reduce the natural hydrogen‐bonding affinity between fibers. In a second report, the same technology will be shown to be advantageous to decrease floc formation in oleophinic composites reinforced with cellulosic fibers. This article summarizes experiments aimed at optimizing the chemistry of deposition of montmorillonite clay onto fiber surfaces. The aim was to optimize the chemical conditions for the heterodeposition of the anionic clay onto cationically charged fluff pulp. The experiments were designed to provide a theoretical framework for the deposition of the nanoclay onto the pulp fibers. High Mw p‐DADMAC and an exfoliated clay (achieved by passing the clay through a homogenizer) were used. As expected, a certain degree of charge overcompensation by adding an electrolyte was necessary to bring about deposition. The adsorbed amount of clay could be calculated from the charge balance between the overcompensated charge and the net clay charge, constituting the theoretical framework for nanoclay heterodeposition. As expected, montmorillonite clay greatly destroyed the joint strength between fibers (determined by evaluating the strength of paper made from treated fibers). The surface coverage (determined by ESCA) was shown to be a linear function of the attached amount of clay, and ∼3% clay was required to fully cover the fiber surfaces. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Isothermal crystallization behavior of hybrid biocomposite consisting of regenerated cellulose fiber, clay, and poly(lactic acid)
Authors: Lee Seung‐Hwan , Wang Siqun , Teramoto Yoshikuni
Published: January 2008

Quantitative analysis of isothermal crystallization kinetics of PLA/clay nanocomposite and PLA/clay/regenerated cellulose fiber (RCF) hybrid composite has been conducted. The crystallization rate constant (k) according to Avrami equation was higher in PLA/clay nanocomposite than in PLA/clay/RCF hybrid composite at the same crystallization temperature. The equilibrium melting temperature obtained by Hoffman–Weeks equation was almost same in both composites, whereas stability parameter was greater in hybrid composite than in nanocomposite. Activation energy of hybrid composite for crystallization was larger than that of nanocomposite. The value of nucleation parameter (Kg) and surface free energy (se) of hybrid composite were larger than nanocomposite, indicating that hybrid composite has a less folding regularity than nanocomposite. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Analysis of the cure of epoxy based layered silicate nanocomposites: Reaction kinetics and nanostructure development
Authors: Montserrat S. , Román F. , Hutchinson J. M. , Campos L.
Published: January 2008

The cure reaction kinetics of epoxy resin, with organically modified montmorillonite loadings of up to 20 wt % and with stoichiometric conditions, has been studied by differential scanning calorimetry with a view to understanding further the fabrication of epoxy‐based polymer layered silicate nanocomposites. The kinetic analysis of isothermal and nonisothermal cure shows that the autocatalytic model is the more appropriate to describe the kinetics of these reactions, and it is observed that a dominant effect of the montmorillonite is to catalyze the curing reaction. However, it was not possible to model the reactions over the whole range of degrees of conversion, in particular for nonisothermal cure. This attributed to the complexity of the reactions, and especially to the occurrence of etherification by cationic homopolymerization catalyzed by the onium ion of the organically modified montmorillonite. The homopolymerization reaction results in an excess of diamine in the system, and hence in practice the reaction is off stoichiometric, which leads to a reduction in both the heat of cure and the glass transition temperature as the montmorillonite content increases. Small angle X‐ray scattering of the cured nanocomposites shows that an exfoliated nanostructure is obtained in nonisothermal cure at slow heating rates, whereas for nonisothermal cure at faster heating rates, as well as for isothermal cure at 70°C and 100°C, a certain amount of exfoliation is accompanied by the growth of d‐spacings of 1.4 nm and 1.8 nm for dynamic and isothermal cure, respectively, smaller than the d‐spacings of the modified clay before intercalation of the resin. A similar nanostructure, consisting of extensive exfoliation accompanied by a strong scattering at distances less than the d‐spacing of the modified clay, is also found for resin/clay mixtures, before the addition of any crosslinking agent, which have been preconditioned by storage for long times at room temperature. The development of these nanostructures is attributed to the presence of clay agglomerations in the original resin/clay mixtures and highlights the importance of the quality of the dispersion of the clay in the resin in respect of achieving a homogeneous exfoliated nanostructure in the cured nanocomposite. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Stress‐relaxation behavior of natural rubber/polystyrene and natural rubber/polystyrene/natural rubber‐graft‐polystyrene blends
Authors: Asaletha R. , Bindu P. , Aravind Indose , Meera A. P. , Valsaraj S. V. , Yang Weimin , Thomas Sabu
Published: January 2008

We studied the stress‐relaxation behavior of natural rubber (NR)/polystyrene (PS) blends in tension. The effects of strain level, composition, compatibilizer loading, and aging on the stress‐relaxation behavior were investigated in detail. The dispersed/matrix phase morphology always showed a two‐stage mechanism. On the other hand, the cocontinuos morphology showed a single‐stage mechanism. The addition of a compatibilizer (NR‐g‐PS) into 50/50 blends changed the blend morphology to a matrix/dispersed phase structure. As a result, a two‐step relaxation mechanism was found in the compatibilized blends. A three‐stage mechanism was observed at very high loadings of the compatibilizer (above the critical micelle concentration), where the compatibilizer formed micelles in the continuous phase. The aged samples showed a two‐stage relaxation mechanism. The rate of relaxation increased with strain levels. The aging produced interesting effects on the relaxation pattern. The rate of relaxation increased with temperature due to the degradation of the samples. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Influence of attapulgites on cure‐reaction‐induced phase separation in epoxy/poly(ether sulfone) blends
Authors: Zhao Lin , Zhan Guozhu , Yu Yingfeng , Tang Xiaolin , Li Shanjun
Published: January 2008

The influence of attapulgites (ATTs) on cure‐reaction‐induced phase separation in diglycidyl ether of bisphenol A/poly(ether sulfone) (PES) blends has been studied with scanning electron microscopy (SEM), transmission electron microscopy (TEM), optical microscopy, time‐resolved light scattering, and dynamic mechanical analysis at different ATT and PES concentrations. The SEM results show that the incorporation of a small amount of ATT into the blends can change the final phase morphology markedly and affect the secondary phase separation. The TEM results show that ATT particles are pinned down by the interfacial tension at the phase interfaces, and this slows the interfacial motion. In addition, the incorporation of a small amount of ATT particles can improve the modulus because of the increased interfacial interaction of the PES‐rich and epoxy‐rich phases. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Shape‐memory behaviors of biodegradable poly(L‐lactide‐co‐ϵ‐caprolactone) copolymers
Authors: Lu X. L. , Cai W. , Gao Z. Y.
Published: January 2008

A series of biodegradable poly(L‐lactide‐co‐ϵ‐caprolactone) (PCLA) copolymers with different chemical compositions are synthesized and characterized. The mechanical properties and shape‐memory behaviors of PCLA copolymers are studied. The mechanical properties are significantly affected by the copolymer compositions. With the ϵ‐caprolactone (ϵ‐CL) content increasing, the tensile strength of copolymers decreases linearly and the elongation at break increases gradually. By means of adjusting the compositions, the copolymers exhibit excellent shape‐memory effects with shape‐recovery and shape‐retention rate exceeding 95%. The effects of composition, deformation strain, and the stretching conditions on the recovery stress are also investigated systematically. A maximum recovery stress around 6.2 MPa can be obtained at stretching at Tg − 15°C to 200% deformation strain for the PCLA70 copolymer. The degradation results show that the copolymers with higher ϵ‐CL content have faster degradation rates and shape‐recovery rates, meanwhile, the recovery stress can maintain a relative high value after 30 days in vitro degradation. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Exploring the relationship between feature and perceptual visual spaces
Authors: Rorissa Abebe , Clough Paul , Deselaers Thomas
Published: January 2008

The number and size of digital repositories containing visual information (images or videos) is increasing and thereby demanding appropriate ways to represent and search these information spaces. Their visualization often relies on reducing the dimensions of the information space to create a lower‐dimensional feature space which, from the point‐of‐view of the end user, will be viewed and interpreted as a perceptual space. Critically for information visualization, the degree to which the feature and perceptual spaces correspond is still an open research question. In this paper we report the results of three studies which indicate that distance (or dissimilarity) matrices based on low‐level visual features, in conjunction with various similarity measures commonly used in current CBIR systems, correlate with human similarity judgments.
A New Class of Substrates for Nucleophilic 5‐endo‐trig Cyclization, 2‐Trifluoromethyl‐1‐alkenes: Synthesis of Five‐Membered Hetero‐ and Carbocycles That Bear Fluorinated One‐Carbon Units
Authors: Ichikawa Junji , Iwai Yu , Nadano Ryo , Mori Takashi , Ikeda Masahiro
Published: January 2008

Disfavored 5‐endo‐trig cyclizations were achieved in 2‐trifluoromethyl‐1‐alkenes with a nucleophilic nitrogen, oxygen, sulfur, or carbon atom through 1) intramolecular SN2′ reaction with loss of a fluoride ion or 2) intramolecular nucleophilic addition to the vinylic group. This reaction manifold provides a versatile method for the synthesis of indolines, indoles, pyrrolidines, tetrahydrofurans, 2,3‐dihydrobenzo[b]thiophenes, tetrahydrothiophenes, and cyclopentanes that bear a fluorinated one‐carbon unit such as a difluoromethylene, difluoromethyl, or trifluoromethyl group.
Stereochemistry and Mechanistic Study of Intramolecular PdII‐Catalyzed Oxypalladation and 1,3‐Chirality‐Transfer Reactions
Authors: Uenishi Jun'ichi , Vikhe Yogesh Shankar , Kawai Nobuyuki
Published: January 2008

PdII‐catalyzed cyclizations of chiral ε‐, ζ‐, and η‐hydroxy‐α,β‐unsaturated alcohols are described. The reactions took place stereospecifically to give chiral 2,5‐disubstituted tetrahydrofurans, 2,6‐disubstituted tetrahydropyrans, and 2,7‐disubstituted oxepanes, respectively. The chirality of the carbon center of the chiral allylic alcohol is transferred stereospecifically to the carbon center of the newly generated oxacyclic ring. A plausible reaction mechanism involves 1) chiral‐allylic‐alcohol‐induced syn facioselective formation of a Pd π‐complex, 2) syn oxypalladation, and 3) syn elimination of PdCl(OH), which provide a rational account for the stereochemical results.
Determination of lipoprotein lipase activity in post heparin plasma of streptozotocin‐induced diabetic rats by high‐performance liquid chromatography with fluorescence detection
Authors: Chou Yu‐Ching , Tsai Yih‐Chiao , Chen Chien‐Ming , Chen Shih‐Ming , Lee Jen‐Ai
Published: January 2008

The activity of lipoprotein lipase (LPL), an enzyme responsible for lipoprotein metabolism, would vary in diseases and metabolic disorders. For determination of LPL activity, a highly sensitive high performance liquid chromatography (HPLC) method using a fluorescent reagent, 4‐nitro‐7‐piperazino‐2,1,3‐benzoxadiazole (NBD‐PZ) was applied to determinate the oleic acid (OA) generated from triolein by LPL activity without multiple solvents extraction step. We studied the optimal conditons of the reaction including the effect of emulsifiers, deproteinizing solvents, and the concentration of bovine serum albumin (BSA). Ten millimolar concentrations of triolein, 5% of BSA, 1% of Gum arabic (GA), and acetonitrile showed the optimum conditions for measuring the LPL activity. The accuracy values for the determination of LPL activity in 10 µL of rat post heparin plasma were 108.73 ∼ 114.36%, and the intra‐ and inter‐day precision values were within 1.28% and 2.91%, respectively. The limit of detection was about 4.53 nM (signal‐to‐noise ratio 3).

The proposed method was applied to determination of LPL activity in post heparin plasma of normal and streptozotocininduced diabetic rats associated with 52.3% reduction. The established assay system could be used for determining LPL activity in different physiological and pathological conditions to clarify the relationship between LPL activity and diabetes mellitus. Copyright © 2008 John Wiley & Sons, Ltd.
Simultaneous determination of tanshinone I, dihydrotanshinone I, tanshinone IIA and cryptotanshinone in rat plasma by liquid chromatography–tandem mass spectrometry: application to a pharmacokinetic study of a standardized fraction of Salvia miltiorrhiza, PF2401‐SF
Authors: Park Eun Jeong , Ji Hye Young , Kim Nam Jin , Song Won Young , Kim Young Hoon , Kim Youn‐Chul , Sohn Dong Hwan , Lee Hye Suk
Published: January 2008

A rapid, sensitive and selective liquid chromatography–tandem mass spectrometric (LC‐MS/MS) method for the simultaneous determination of tanshinone I, dihydrotanshinone I, tanshinone IIA and cryptotanshinone, the active components of Salvia miltiorrhiza in rat plasma, was developed. After liquid–liquid extraction with tariquidar as an internal standard, tanshinone I, dihydrotanshinone I, tanshinone IIA and cryptotanshinone were eluted from an Atlantis dC18 column within 5 min with a mixture of methanol and ammonium formate (10 mm, pH 6.5; 85:15, v/v). The analytes were detected by an electrospray ionization tandem mass spectrometry in the selected reaction monitoring (SRM) mode. The standard curves were linear (r = 0.999) over the concentration range of 0.25–80 ng/mL for tanshinone I, dihydrotanshinone I, tanshinone IIA and cryptotanshinone in rat plasma. The coefficients of variation and the relative errors of tanshinone I, dihydrotanshinone I, tanshinone IIA and cryptotanshinone for intra‐ and inter‐assay at four quality control (QC) concentrations were 1.1–5.1% and −4.0–6.0%, respectively. The lower limit of quantification for tanshinone I, dihydrotanshinone I, tanshinone IIA and cryptotanshinone was 0.25 ng/mL from 100 µL of plasma. This method was successfully applied to the pharmacokinetic study of tanshinone I, dihydrotanshinone I, tanshinone IIA and cryptotanshinone after oral administration of PF2401‐SF, the standardized fraction of Salvia miltiorrhiza enriched with tanshinone I, dihydrotanshinone I, tanshinone IIA and cryptotanshinone to male Sprague–Dawley rats. Copyright © 2008 John Wiley & Sons, Ltd.
Determination of volatile organic compounds generated from fresh, white and red Panax ginseng (C. A. Meyer) using a direct sample injection technique
Authors: Abd El‐Aty A. M. , Kim In‐Kyung , Kim Mi‐Ra , Lee ChiHo , Shim Jae‐Han
Published: January 2008

Ginsenosides are regarded as the main active, non‐volatile components of Panax ginseng (C. A. Meyer). However, throughout the long history of ginseng research, there has been virtually no report describing its volatile flavor compounds. A solvent‐free procedure for the determination of volatile flavor compounds generated from fresh, white and red Panax ginseng (C. A. Meyer) using solvent‐free solid injection (SFSI) coupled with gas chromatography‐mass spectrometry (GC‐MS) detection is described here. At no point in the SFSI technique were the extraction conditions optimized. Rather, the experimental variables including various sample preparations (fresh, oven‐dried and freeze‐dried), injector temperatures (100, 150, 200, 250 and 300°C), and preheating times (3, 5, 7, 10 and 15 min), were predicated on the experience of the authors. A total of 47 compounds were identified in various forms of ginseng. Among the compounds identified in the sample, fresh ginseng was characterized by a high proportion of 3‐acetyl‐1‐(3,4‐dimethoxyphenyl)‐5‐ethyl‐4,5‐dihydro‐7,8‐dimethoxy‐4‐methylene‐3H‐2,3‐benzodiazepine (64.24%) and 23,24‐dinor‐3‐oxolean‐4,12‐dien‐28‐oic acid (21.42%); 2‐furanmethanol (20.26%) and 3‐hydroxy‐2‐methyl‐4H‐pyran‐4‐one (17.95%) were detected as the major components in white ginseng while the main components of the red ginseng were found to be 1,2‐benzenedicarboxylic acid dibutyl ester (16.27%) and 2‐furanmethanol (13.82%). SFSI is a solvent‐free, rapid and simple sample preparation technique based on direct vaporization. There is no dilution or contamination with solvent or its impurities and no loss of quickly eluted components was observed in the solvent peak. Copyright © 2008 John Wiley & Sons, Ltd.
Synthesis and Stability in Biological Media of 1H‐Imidazole‐1‐carboxylates of ROS203, an Antagonist of the Histamine H3Receptor
Authors: Rivara Mirko , Vacondio Federica , Silva Claudia , Zuliani Valentina , Fantini Marco , Bordi Fabrizio , Plazzi Pier Vincenzo , Bertoni Simona , Ballabeni Vigilio , Flammini Lisa , Barocelli Elisabetta , Mor Marco
Published: January 2008

A series of carbamate derivatives of the H3antagonist ROS203 (1) were prepared, and their lipophilicity and steric hindrance were modulated by introducing linear or branched alkyl chains of various lengths.In vitrostability studies were conducted to evaluate how structural modulations affect the intrinsic reactivity of the carbamoyl moiety and its recognition by metabolic enzymes. Linear alkyl carbamates were the most susceptible to enzymatic hydrolysis, with bioconversion rates being higher in rat liver and plasma. Chain ramification significantly enhanced the enzymatic stability of the set, with two derivatives (1gand1h) being more stable by a factor of 8–40 than the ethyl carbamate1a. Incubation with bovine serum albumin (BSA) showed a protective role of proteins on chemical and porcine‐liver esterase (PLE)‐catalyzed hydrolysis.Ex vivobinding data afteri.v.administration of1hrevealed prolonged displacement of the labeled ligand [3H]‐(R)‐α‐methylhistamine ([3H]RAMHA) from rat‐brain cortical membranes, when compared to1. However, the high rates of bioconversion in liver, as well as the chemical instability of1h, suggest that further work is needed to optimize the enzymatic and chemical stability of these compounds.
Non‐Nucleoside HIV‐1 Reverse‐Transcriptase Inhibitors. Part 10
Authors: Wang Yueping , Chen Fen‐Er , Balzarini Jan , De Clercq Erik , Pannecouque Christophe
Published: January 2008

A series of structurally related 2,5‐disubstituted 6‐(1‐naphthylmethyl)‐pyrimidin‐4(3H)‐ones, compounds 6a–6r, were synthesized and evaluated for their in vitro anti‐HIV activities in MT‐4 cells. Most of the new compounds investigated showed moderate‐to‐good activities against wild‐type HIV‐1, with IC50 values in the range 5.64–0.21 μM. Compound 6d was the most potent congener (IC50=0.21 μM, SI=724) in inhibiting HIV‐1 replication, which is ca. 25 times more effective than the reference compound 2′,3′‐dideoxyinosine (DDI). Preliminary structure–activity relationship (SAR) studies revealed that both modulation of the amino function at C(2) and of the alkyl group at C(5) of the pyrimidine ring are crucial for high anti‐HIV‐1 activity.
A New Cytotoxic, Apoptosis‐Inducing Triterpenoid from the Rhizomes of Astilbe chinensis
Authors: Zhang Yi‐Bin , Peng Xiao‐Ying , Sun Hong‐Xiang
Published: January 2008

A new ursane‐based compound, astilbotriterpenic acid (1), was isolated from the rhizomes of Astilbe chinensis. Its structure was determined on the basis of chemical evidence and extensive spectroscopic methods, including 1D‐ and 2D‐NMR. The pentacyclic triterpenoid 1 was assayed for its in vitro cytotoxicity against Bcap37, HeLa, HepG2, HO‐8910, K562, PAA, SGC7901, and P388 cancer cells, as well as for its apoptosis‐inducing activity in HeLa cells. Compound 1 was found to strongly inhibit tumor‐cell growth through induction of apoptosis and may, thus, be further evaluated as a novel chemotherapeutic agent.
Synthesis of Oligonucleotide Derivatives Using ChemMatrix Supports
Authors: Mazzini Stefania , García‐Martin Fayna , Alvira Margarita , Aviñó Anna , Manning Brendan , Albericio Fernando , Eritja Ramon
Published: January 2008

The synthesis of oligonucleotides on poly(ethylene glycol)‐based (ChemMatrix) supports was studied. Results show that oligonucleotides can be indeed prepared in good yields using slightly modified synthesis cycles and automated DNA synthesizers. The use of these supports for the synthesis of oligonucleotide–peptide conjugates and for the ligation of oligonucleotides using Cu+‐catalyzed cycloadition reactions is reported. Moreover, these supports can be used for the preparation of oligonucleotides in anhydrous solvents, followed by hybridization of the complementary sequences in aqueous buffers.
Enzymatically Catalyzed DNA Synthesis Using L‐Asp‐dGMP, L‐Asp‐dCMP, and L‐Asp‐dTMP
Authors: Terrazas Montserrat , Marlière Philippe , Herdewijn Piet
Published: January 2008

The replacement of the pyrophosphate moiety of deoxynucleoside triphosphates by L‐aspartic acid allows incorporation of natural deoxynucleosides into DNA using HIV reverse transcriptase (RT) as enzyme, while retaining the canonical base‐pair selectivity. N‐Methylation of the L‐aspartic acid leaving group results in a reduced fidelity of incorporation.
Sugar–Oligoamides: Bound‐State Conformation and DNA Minor‐Groove‐Binding Description by TR‐NOESY and Differential‐Frequency Saturation‐Transfer‐Difference Experiments
Authors: Souard Florence , Muñoz Eva , Peñalver Pablo , Badía Concepción , del Villar‐Guerra Rafael , Asensio Juan Luis , Jiménez‐Barbero Jesús , Vicent Cristina
Published: January 2008

Selective‐frequency saturation‐transfer‐difference (STD) spectra allow the description of complexes established between minor‐groove binders and long tracts of calf thymus DNA (ct‐DNA). Two sets of experiments with selective saturation of either the H1′ or H4′/H5′/H5′′ proton NMR regions of deoxyribose allow the description of the ligand residues close to the inner (H1′) and outer regions (H4′/H5′/H5′′) of the minor groove of double‐helical DNA. A series of complexes of sugar–oligoamides (2–6) with ct‐DNA have been studied by both TR‐NOESY and STD experiments. The binding mode of the complexes is similar to that of netropsin (1) and allows us to define a general binding mode for this family of ligands, in which an NH rim points towards the internal area (inner region) and a CH3 rim points towards the external part (outer region) of the minor groove of DNA. Also by means of both TR‐NOESY and STD experiments, a description of the asymmetric centers of the sugar residue close to the inner and outer regions of the groove has been achieved. These results confirm that the sugar is responsible for the differences previously found in binding energetics.
The Search for a Potentially Prebiotic Synthesis of Nucleotides via Arabinose‐3‐phosphate and Its Cyanamide Derivative
Authors: Anastasi Carole , Buchet Fabien F. , Crowe Michael A. , Helliwell Madeleine , Raftery Jim , Sutherland John D.
Published: January 2008

For the RNA world hypothesis to be accepted, the constitutional self‐assembly of RNA will have to be demonstrated. Conceptually, the simplest route to RNA involves nucleotide polymerisation. Activated pyrimidine nucleotides can be derived from arabinose‐3‐phosphate under potentially prebiotic conditions, but the prebiotic synthesis of this sugar phosphate has not hitherto been investigated. The results of synthetic approaches involving phosphorylation, phosphate migration and 2,3‐CC bond construction are described herein.
Structural Changes and Coordinatively Unsaturated Metal Atoms on Dehydration of Honeycomb Analogous Microporous Metal–Organic Frameworks
Authors: Dietzel Pascal D. C. , Johnsen Rune E. , Blom Richard , Fjellvåg Helmer
Published: January 2008

Porous metal–organic framework compounds with coordinatively unsaturated metal sites on the inner surface of the pores promise to be valuable adsorbents and catalyst systems, either in industrial applications or as model systems to study interactions with guest molecules. The dehydration process of two isostructural microporous coordination polymers, [M2(dhtp)(H2O)2]⋅8 H2O, termed CPO‐27‐M (M=Co, Zn; H4dhtp=2,5‐dihydroxyterephthalic acid) was investigated by in situ variable temperature X‐ray diffraction. Both compounds contain accessible coordination sites at the metal after complete removal of the solvent. However, despite the analogy of their crystal structures, they behave differently during dehydration. For CPO‐27‐Co, water desorption is a smooth topotactic process of second order with no concomitant space group change and no increase in microstrain, which is beneficial for the applicability of the material. Removal of the water propagates from the center of the channels outwards. The coordinating water molecule at the metal desorbs only when almost all the bulk water in the pores has disappeared. In contrast, discontinuities in the powder pattern of CPO‐27‐Zn indicate the occurrence of first‐order transitions. The crystal structures of four of the five individual phases could be determined. The structure of the intermediate phase occurring just before the framework is completely evacuated was elusive in respect to full structure solution and refinement, but it is most probably related to the removal of the axis of threefold symmetry. The zinc‐based material experiences a significant amount of strain.
Enantioselective oxidation of sulfides catalyzed by titanium complexes of 1,2‐diarylethane‐1,2‐diols: Effect of the aryl substitution
Authors: Superchi Stefano , Scafato Patrizia , Restaino Lina , Rosini Carlo
Published: January 2008

The effects of the substitution on the aryl moiety on the asymmetric oxidation of sulfides mediated by Ti‐complexes of chiral 1,2‐diarylethane‐1,2‐diols were investigated. The substitution of the aryl ring of the diol with both EWG and EDG substituents generally decreased the enantioselectivity with respect to the use of unsubstituted 1,2‐diphenylethane‐1,2‐diol (1a). Only in the presence of 1,2‐di(4‐t‐butyl)phenyl‐1,2‐diol (1g) were higher ee's obtained with aryl methyl and aryl benzyl sulfides affording ee's up to 90 and 99%, respectively. Lower ee's were achieved with larger naphthyl and aryl alkyl sulfides. Contrary to the other Ti‐alcoholates used in the oxidation of sulfides, the Ti‐complex of diol 1g was soluble in hexane, allowing us to perform the process with high enantioselectivity in this solvent, with great environmental advantages over the commonly used chlorinated solvents. Chirality, 2008. © 2008 Wiley‐Liss, Inc.
Fluorous “racemic” mixture synthesis: Polysaccharide‐based chiral columns for simultaneous demix and enantioseparation of racemic fluorous tagged compounds
Authors: Tonoi Takayuki , Zhang Wei , Curran Dennis P. , Mikami Koichi
Published: January 2008

The proof of concept experiments of fluorous “racemic” mixture synthesis (FRMS) is shown using polysaccharide‐based chiral stationary phases. The mixture of racemic O‐benzoylmandelate derivatives bearing different lengths of fluorous cleavable tags undergoes sequential reactions to provide individual derivatives as well as their enantiomers resolved on polysaccharide‐based chiral HPLC columns (DAICEL CHIRALCEL® and CHIRALPAK® series). Chirality, 2008. © 2008 Wiley‐Liss, Inc.
Generation of Carrier Peptides for the Delivery of Nucleic Acid Drugs in Primary Cells
Authors: Rennert Robert , Neundorf Ines , Jahnke Heinz‐Georg , Suchowerskyj Philipp , Dournaud Pascal , Robitzki Andrea , Beck‐Sickinger Annette G.
Published: January 2008

Now that the human genome has been decoded, the demand for novel therapeutic concepts, such as gene and stem cell therapy, is higher than ever before. Although new and better pharmaceutical agents are available, their efficient delivery to the intracellular site of action is still a serious challenge. A possible solution to this problem is the use of cell‐penetrating peptides as delivery vectors, including derivatives of human calcitonin (hCT). The aim of this study was to synthesise novel branched hCT‐derived peptides for the noncovalent delivery of nucleic acids. The uptake of the resulting oligocationic peptides into various cell lines as well as primary cells was monitored by fluorescence microscopy. To determine the appropriate peptide–plasmid charge ratios for efficient cell transfection, electromobility shift assays were carried out. Finally, flow cytometric and fluorescence microscopic studies of gene expression highlighted two novel hCT‐derived peptides as highly effective in the delivery of noncovalently complexed plasmid DNA. Thus, the absence of cytotoxicity paired with highly efficient cell internalisation and transfection rates, in primary cells as well, make both peptides powerful candidates as drug delivery vectors, especially for plasmid DNA, for both in vivo and ex vivo therapeutic applications.