bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular modeling of metal complexation by a fluoroquinolone antibiotic
Authors: Aristilde Ludmilla , Sposito Garrison
Published: June 2008

An understanding of the factors controlling the chemodynamics of fluoroquinolone antibiotics in different environmental matrices is a necessary prerequisite to the assessment of their potential impact on nontarget organisms in soils and receiving waters. Of particular interest are the complexes formed between fluoroquinolones and metal cations, which are believed to be important in the mechanism of sequestration of the antibiotic by minerals and natural organic matter. The structures of these complexes have not been fully resolved by conventional spectroscopy; therefore, molecular simulations may provide useful complementary insights. We present results from apparently the first molecular dynamics simulations of a widely used fluoroquinolone antibiotic, ciprofloxacin (Cipro), in aqueous complexes with five metal cations typically found in soils and surface waters: Ca2+, Mg2+, Fe2+, Na+, and K+. The interatomic potential functions employed in the simulations were validated by comparison with available structural data for solid-phase Cipro-hexahydrate and for the metal cations in aqueous solution. Although no comprehensive structural data on the aqueous complexes appear to be available, properties of the metal complexes predicted by our simulations agree with available data for solid-phase metal–Cipro complexes. Our results indicate that the ionic potential of the metal cation controls the stability of the complex formed and that the hydration number of the metal cation in aqueous solution determines its coordination number with O atoms in the metal–Cipro complex. In respect to environmental chemodynamics, our results imply that Cipro will form two configurations of bidendate chelates with metal centers on exposed surfaces of mineral oxides, water-bridged surface complexes with exchangeable cations in clay mineral interlayers, and cation-bridged complexes with functional groups in natural organic matter.
Metabolic Phenotypes, Vascular Complications, and Premature Deaths in a Population of 4,197 Patients With Type 1 Diabetes
Authors: Mäkinen Ville-Petteri , Forsblom Carol , Thorn Lena M. , Wadén Johan , Gordin Daniel , Heikkilä Outi , Hietala Kustaa , Kyllönen Laura , Kytö Janne , Rosengård-Bärlund Milla , Saraheimo Markku , Tolonen Nina , Parkkonen Maija , Kaski Kimmo , Ala-Korpela Mika , Groop Per-Henrik ,   on behalf of the FinnDiane Study Group
Published: June 2008

OBJECTIVE—Poor glycemic control, elevated triglycerides, and albuminuria are associated with vascular complications in diabetes. However, few studies have investigated combined associations between metabolic markers, diabetic kidney disease, retinopathy, hypertension, obesity, and mortality. Here, the goal was to reveal previously undetected association patterns between clinical diagnoses and biochemistry in the FinnDiane dataset.

RESEARCH DESIGN AND METHODS—At baseline, clinical records, serum, and 24-h urine samples of 2,173 men and 2,024 women with type 1 diabetes were collected. The data were analyzed by the self-organizing map, which is an unsupervised pattern recognition algorithm that produces a two-dimensional layout of the patients based on their multivariate biochemical profiles. At follow-up, the results were compared against all-cause mortality during 6.5 years (295 deaths).

RESULTS—The highest mortality was associated with advanced kidney disease. Other risk factors included 1) a profile of insulin resistance, abdominal obesity, high cholesterol, triglycerides, and low HDL2 cholesterol, and 2) high adiponectin and high LDL cholesterol for older patients. The highest population-adjusted risk of death was 10.1-fold (95% CI 7.3–13.1) for men and 10.7-fold (7.9–13.7) for women. Nonsignificant risk was observed for a profile with good glycemic control and high HDL2 cholesterol and for a low cholesterol profile with a short diabetes duration.

CONCLUSIONS—The self-organizing map analysis enabled detailed risk estimates, described the associations between known risk factors and complications, and uncovered statistical patterns difficult to detect by classical methods. The results also suggest that diabetes per se, without an adverse metabolic phenotype, does not contribute to increased mortality.
Translating the A1C Assay Into Estimated Average Glucose Values
Authors: Nathan David M. , Kuenen Judith , Borg Rikke , Zheng Hui , Schoenfeld David , Heine Robert J. ,   for the A1c-Derived Average Glucose (ADAG) Study Group
Published: June 2008

OBJECTIVE—The A1C assay, expressed as the percent of hemoglobin that is glycated, measures chronic glycemia and is widely used to judge the adequacy of diabetes treatment and adjust therapy. Day-to-day management is guided by self-monitoring of capillary glucose concentrations (milligrams per deciliter or millimoles per liter). We sought to define the mathematical relationship between A1C and average glucose (AG) levels and determine whether A1C could be expressed and reported as AG in the same units as used in self-monitoring.

RESEARCH DESIGN AND METHODS—A total of 507 subjects, including 268 patients with type 1 diabetes, 159 with type 2 diabetes, and 80 nondiabetic subjects from 10 international centers, was included in the analyses. A1C levels obtained at the end of 3 months and measured in a central laboratory were compared with the AG levels during the previous 3 months. AG was calculated by combining weighted results from at least 2 days of continuous glucose monitoring performed four times, with seven-point daily self-monitoring of capillary (fingerstick) glucose performed at least 3 days per week.

RESULTS—Approximately 2,700 glucose values were obtained by each subject during 3 months. Linear regression analysis between the A1C and AG values provided the tightest correlations (AGmg/dl = 28.7 × A1C − 46.7, R2 = 0.84, P < 0.0001), allowing calculation of an estimated average glucose (eAG) for A1C values. The linear regression equations did not differ significantly across subgroups based on age, sex, diabetes type, race/ethnicity, or smoking status.

CONCLUSIONS—A1C levels can be expressed as eAG for most patients with type 1 and type 2 diabetes.
Impact of the lower energy threshold on the NEMA NU2-2001 count-rate performance of a LSO based PET-CT scanner
Authors: Herzog H. , Schäfers K. P. , Käpplinger S. , Schober O. , Eckardt J.
Published: June 2008

The aim of this study was to investigate the impact of the lower energy threshold (LET) on the NEMA NU2–2001 count-rate performance of a LSO-based PET scanner (Siemens PET-CT Biograph Sensation 16). The quantitative measurements were focused on three different aspects: noise equivalent count rate (NEC), scatter fraction, and absolute sensitivity. Methods: According to the NEMA-NU2–2001 protocol count-rate-performance (NEC-2R, scatter fraction) and sensitivity were evaluated performing serial measurements at LETs of 350, 375, 400, 410, 420, 430, 440, and 450 keV (the upper energy threshold was fixed to 650 keV). NEMA protocols were adapted to account for the intrinsic radioactivity of 176Lu in the LSO crystals. Results: Up to a radioactivity concentration of 8 kBq/ml the highest NECrates were obtained at an LET of 410 keV, between 8 and 20 kBq/ml at an LET of 420 keV and above 20 kBq/ml at an LET of 430 keV. The overall NEC maximum was 67 kcps at 430 keV (at 28 kBq/ml). The minimum scatter fraction was measured at a radioactivity concentration of ~ 0.5 kBq/ml. The scatter fraction decreased continuously from 45% at an energy threshold of 350 keV to 24% at 450 keV. The maximum sensitivity of 5.8 kcps/MBq, was obtained at an LET of 350 keV and the minimum sensitivity of 4.2 kcps/MBq at an LET of 450 keV. At the LET with the maximum NEC-rate (430 keV) the sensitivity was 4.8 kcps/MBq. Conclusion: The optimal count-rate performance of the LSO-based PET system was found at LETs between 410 keV and 430 keV depending on the actual radioactivity concentration placed in the scanner. A global maximum in NEC count rate was obtained at an LET of 430 keV.
FROM MODELLING TOOLS TOWARDS THE MARKET ITSELF ‐AN OPPORTUNITY FOR SUSTAINABILITY ASSESSMENT?
Authors: Kauko Tom
Published: June 2008

Market based analyses of residential property value traditionally fall within two broad research traditions: a ‘ more practical'value analysis tradition and a ‘ more academic’ market analysis tradition. While there is a steady flow of information from the latter to the former direction, until recently very little such information diffusion has occurred from the former to the latter modelling tradition. In such a learning process, the value modelling performance could serve as a guideline for what kind of market model is valid and feasible for a given dataset with certain recognisable tendencies. On the other hand, the characterisation of particular market circumstances is a key determinant of real estate sustainability. A sustainable market generates a sustainable value, which then can be used as an attractiveness indicator in a broader sense; or in the opposite case, an unsustainable market diagnoses a problem in unsustainable value. Santrauka Gyvenamosios nuosavybės vertės analizės pagal rinkas paprastai skirstomos į dvi plačias tiriamojo darbo tradicijas: „praktiškesnę“ vertės analizės tradiciją ir „akademiškesnę“ rinkos analizės tradiciją. Nors akademinės analizės informacija nuolatos pasiekia praktiškąją pusę, dar visai neseniai informacijos tekėjimas iš praktiškosios pusės į akademinę buvo labai nedidelis. Naudojant tokį mokymosi procesą, vertės modeliavimas galėtų tapti gairėmis, nustatant, kuris rinkos modelis yra veiksmingas ir įmanomas pagal turimus duomenis su tam tikromis atpažįstamomis tendencijomis. Kita vertus, konkrečių rinkos aplinkybių charak te ri za vimas – pagrindinis lemiamas veiksnys, darantis įtaką nekilnojamojo turto darnai. Darni rinka kuria subalansuotą vertę, kurią vėliau galima naudoti kaip patrauklumo rodiklį platesniąja prasme, o priešingu atveju, nedarni rinka rodo nesubalansuotos vertės problemą.
New Pathway to C2‐Symmetric Atropoisomeric Bipyridine N,N′‐Dioxides and Solvent Effect in Enantioselective Allylation of Aldehydes
Authors: Hrdina Radim , Dračínský Martin , Valterová Irena , Hodačová Jana , Císařová Ivana , Kotora Martin
Published: June 2008

The [2+2+2] cyclotrimerization of 1,7,9,15‐hexadecatetrayne with nitriles catalyzed by dicarbonylcyclopentadienylcobalt(I) opened a new pathway for the synthesis of C2‐symmetrical bis(tetrahydroisoquinolines) that were used as starting material for the preparation of axially chiral bipyridine N,N′‐dioxides. The N,N′‐dioxides (1 mol%) were found to be highly catalytically active and enantioselective (up to 83% ee) for the asymmetric allylation of aldehydes with allyl(trichloro)silane in various solvents. In addition, a dramatic solvent effect was observed where the use of different solvents induced opposite chiralities of the product with the same enantiomer of the catalyst, e.g., 65% ee (S) in acetonitrile (MeCN) vs. 82% ee (R) in chlorobenzene.
Physical work capacity in older adults: Implications for the aging worker
Authors: Kenny Glen P. , Yardley Jane E. , Martineau Lucie , Jay Ollie
Published: June 2008

Background

In many developed countries, the workforce is rapidly aging. Occupational demands however, have not decreased despite the fact that workers see a decline in physical work capacity with age. The purpose of this review is to examine the physiological adaptations to aging, the impact of aging on performance and the benefits of physical fitness in improving functional work capacity in aging individuals.

Methods

An extensive search of the scientific literature was performed, acquiring published articles which examined the physiological changes associated with age‐related decrements in the physical work capacity of healthy aging adults. The databases accessed included AARP Ageline, AccessScience, Annual Reviews, CISTI, Cochrane Library, Clinical Evidence, Digital Dissertations (Proquest), Embase, HealthSTAR, Medline, PubMed, Scopus, and PASCAL and included relevant information sites obtained on the world wide web.

Results

While a great deal of variation exists, an average decline of 20% in physical work capacity has been reported between the ages of 40 and 60 years, due to decreases in aerobic and musculoskeletal capacity. These declines can contribute to decreased work capacity, and consequential increases in work‐related injuries and illness. However, differences in habitual physical activity will greatly influence the variability seen in individual physical work capacity and its components. Well‐organized, management‐supported, work‐site health interventions encouraging physical activity during work hours could potentially decrease the incidence of age‐related injury and illness.

Conclusions

Age‐associated functional declines and the accompanying risk of work‐related injury can be prevented or at least delayed by the practice of regular physical activity. Older workers could optimally pursue their careers until retirement if they continuously maintain their physical training. Am. J. Ind. Med. 51:610–625, 2008. © 2008 Wiley‐Liss, Inc.
Association between depression and the Gln460Arg polymorphism of P2RX7 Gene: A dimensional approach
Authors: Hejjas Krisztina , Szekely Anna , Domotor Eszter , Halmai Zsuzsa , Balogh Gabriella , Schilling Boglarka , Sarosi Andrea , Faludi Gabor , Sasvari‐Szekely Maria , Nemoda Zsofia
Published: June 2008

The P2RX7 gene (coding for P2X7 purinergic receptor) has been suggested as a novel candidate gene for major depressive disorder (MDD) and bipolar disorder (BPD). The proposed risk allele (G‐allele) of the rs2230912 polymorphism results in an amino acid change at the 460th position, marking this genetic variation a possibly functional one. Here we present a case–control analysis of 171 patients diagnosed with MDD or BPD and 178 controls, as well as a dimensional approach using the Hospital Anxiety and Depression Scale (HADS) for studying the Gln460Arg polymorphism of the P2RX7 gene as a genetic risk factor in depression. While case–control analysis did not show significant difference between the groups, a significant association was found between the P2RX7 polymorphism and the HADS scales in the clinical group (MANOVA P = 0.001). Both anxiety and depression scores increased as the number of G‐allele increased in the genotype groups (ANOVA for HADS‐anxiety: P = 0.01, HADS‐depression: P < 0.001). A significant interaction of clinical status and the P2RX7 polymorphism was also found for the depression scale (MANOVA P = 0.025, subsequent ANOVA for anxiety: P = 0.252; depression: P = 0.002). Whereas patients with G‐allele‐present genotypes showed more elevated depression scores, level of depression in the control group was not affected by the P2RX7 genotype. In conclusion, case–control analysis did not reveal significant results, but using a symptom severity scale we could support the association between depressive disorder and the G‐allele of the Gln460Arg polymorphism in the P2RX7 gene. © 2008 Wiley‐Liss, Inc.
A polymorphism of the neuregulin 1 gene (SNP8NRG243177/rs6994992) affects reactivity to expressed emotion in schizophrenia
Authors: Kéri Szabolcs , Kiss Imre , Seres Imola , Kelemen Oguz
Published: June 2008

A single nucleotide polymorphism of the neuregulin 1 gene (SNP8NRG243177/rs6994992) increases the risk of psychosis, affects prefrontal activation and structural connectivity in the brain, and is related to the expression of a specific neuregulin 1 isoform. The purpose of this study was to investigate the interaction between this polymorphism and reactivity to psychosocial stress. Two hundred patients with schizophrenia were genotyped. The patients and one of their family members participated in neutral and conflict‐related interactions in which the number of relatives' criticisms and patients' unusual thoughts was assessed. Patients with the risk T/T genotype expressed more unusual thoughts than C‐carriers (C/T and C/C) during conflict‐related interactions but not during neutral interactions. Two controls polymorphisms of the neuregulin 1 gene (rs10954867 and rs7005288) showed no such effect. These results raise the possibility that there is a significant gene by environment interaction regarding SNP8NRG243177/rs6994992 and psychosocial stress. © 2008 Wiley‐Liss, Inc.
An unusual incident of adoption in a wild chimpanzee (Pan troglodytes) population at Gombe National Park
Authors: Wroblewski Emily E.
Published: June 2008

Allomothering and adoption are well documented across primate species. Multiple hypotheses have been proposed to explain the evolution of such behavior according to the costs and benefits to the caregiver, mother, and infant. Permanent adoptions and allomothering have been observed in chimpanzees, but they typically involve the infants' siblings or nulliparous females. Here, I report a unique incident of adoption where an infant was adopted by its grandmother without the death of its mother. I conclude by considering how the adoption may have benefited the grandmother, mother, and infant. Am. J. Primatol. 70:995–998, 2008. © 2008 Wiley‐Liss, Inc.
Catalytic Reduction of Dinitrogen to Ammonia by Molybdenum: Theory versus Experiment
Authors: Schrock Richard R.
Published: June 2008

Molybdenum complexes that contain the triamidoamine ligand [(RNCH2CH2)3N]3− (R=3,5‐(2,4,6‐iPr3C6H2)2C6H3) catalyze the reduction of dinitrogen to ammonia at 22 °C and 1 atm with protons from 2,6‐dimethylpyridinium and electrons from decamethylchromocene. Several theoretical studies have been published that bear on the proposed intermediates in the catalytic dinitrogen reduction reaction and their reaction characteristics, including DFT calculations on [(HIPTNCH2CH2)3N]Mo species (HIPT=hexaisopropylterphenyl=3,5‐(2,4,6‐iPr3C6H2)2C6H3), which contain the actual triamidoamine ligand that is present in catalytic intermediates. Recent theoretical findings are compared with experimental findings for each proposed step in the catalytic reaction.
Observation of a System of Linear Loops Formed by Re‐Growing Hairs on Rat Skin
Authors: Liu Li‐Yuan , Guo Dong‐Sheng , Xin Xiu‐Yu , Fang Jin
Published: June 2008

This paper details linear hair re‐growth patterns observed in rats. Adult rats were shaved and observed. The first wave of hair re‐growth did not distribute everywhere, but along specific craniocaudally‐oriented lines. The hair‐lines were 2–15 mm wide and ran from the head, through the torso to the limbs, and were symmetrical along the left and right sides of the body. The symmetric hair‐lines from both sides of the body converged around the mouth, nose, and at the pubic region or ventral midline to form a system of hair‐loop‐lines (HLLs). The loops can be differentiated into four main patterns. The Dorsal Loop and the Lateral Dorsal Loop run along the dorsum and hindlimb. The Ventral Loop and Lateral Ventral Loop travel along the thorax, abdomen, and forelimb. These hair‐lines coincide with our previously observed sympathetic‐substance lines (SSLs) in the rat's skin. Histological observation indicates that rat hair follicles along the hair‐lines were at anagen phase. The catecholamine histofluorescent check showed abundant sympathetic nerve fibers beneath the hair‐lines. After the rats' hairs were dyed, and selected portions shaved, re‐growth was only observed on the shaved portions, indicating that the linear hair growth closely correlated with the shaving. Lastly we examine the cause of the preferential re‐growth and briefly discuss the purpose and physiological role of the HLL. Anat Rec, 291:858–868, 2008.© 2008 Wiley‐Liss, Inc.
Immunohistochemical Analysis of Nucleotide Excision Repair Factors XPA and XPB in Adult Rat Brain
Authors: Yang Shan‐Zheng , Zhang Yi‐Fan , Zhang Ling‐Mei , Huang Ya‐Ling , Sun Feng‐Yan
Published: June 2008

To study the regional and cellular distribution of xeroderma pigmentosum group A and B (XPA and XPB) proteins, two nucleotide excision repair (NER) factors, in the mammalian brain we used immunohistochemistry and triple fluorescent immunostaining combined with confocal microscope scanning in brain slices of adult rat brain, including the cerebral cortex, striatum, substantia nigra compacta, ventral tegmental area, red nucleus, hippocampus, and cerebellum. Both XPA and XPB proteins were mainly expressed in neurons, because the XPA‐ or XPB‐immunopositive cells were only costained with NeuN, a specific neuronal marker, but not with glial fibrillary acidic acid, a specific astrocyte marker, in the striatum. Furthermore, XPA‐ and XPB‐positive staining were observed in the neuronal nuclei. Such subcellular distribution was consistent with the location of the NER in the cells. This study provides the first evidence that NER factors XPA and XPB exist in the nuclei of neurons in the brain, suggesting that the NER may play important roles in the process of DNA repair in adult brain neurons. Anat Rec, 291:775–780, 2008. © 2008 Wiley‐Liss, Inc.
The Major/Minor Concept: Dependence of the Selectivity of Homogeneously Catalyzed Reactions on Reactivity Ratio and Concentration Ratio of the Intermediates
Authors: Schmidt Thomas , Dai Zhenya , Drexler Hans‐Joachim , Hapke Marko , Preetz Angelika , Heller Detlef
Published: June 2008

The homogeneously catalyzed asymmetric hydrogenation of prochiral olefins with cationic RhI complexes is one of the best‐understood selection processes. For some of the catalyst/substrate complexes, experimental proof points out the validation of the major/minor principle; the concentration‐deficient minor substrate complex, which has very high reactivity, yields the excess enantiomer. As exemplified by the reaction system of [Rh(dipamp)(MeOH)2]+/methyl (Z)‐α‐acetamidocinnamate (dipamp=1,2‐bis((o‐methoxyphenyl)phenylphosphino)ethane), all six of the characteristic reaction rate constants have been previously identified. Recently, it was found that the major substrate complex can also yield the major enantiomer (lock‐and‐key principle). The differential equation system that results from the reaction sequence can be solved numerically for different hydrogen partial pressures by including the known equilibrium constants. The result displays the concentration–time dependence of all species that exist in the catalytic cycle. On the basis of the known constants as well as further experimental evidence, this work focuses on the examination of all principal possibilities resulting from the reaction sequence and leading to different results for the stereochemical outcome. From the simulation, the following conclusions can be drawn: 1) When an intermediate has extreme reactivity, its stationary concentration can become so small that it can no longer be the source of product selectivity; 2) in principle, the major/minor and lock‐and‐key principles can coexist depending on the applied pressure; 3) thermodynamically determined intermediate ratios can be completely converted under reaction conditions for a selection process; and 4) the increase in enantioselectivity with increasing hydrogen partial pressure, a phenomenon that is experimentally proven but theoretically far from being well‐understood, can be explained by applying both the lock‐and‐key as well as the major/minor principle.
A Supported Rhodium Hydroxide Catalyst: Preparation, Characterization, and Scope of the Synthesis of Primary Amides from Aldoximes or Aldehydes
Authors: Fujiwara Hiroshi , Ogasawara Yoshiyuki , Kotani Miyuki , Yamaguchi Kazuya , Mizuno Noritaka
Published: June 2008

A supported rhodium hydroxide catalyst, Rh(OH)x/Al2O3 (x=3), is prepared by the reaction of Al2O3 with RhCl3 in an aqueous medium followed by treatment with NaOH. The RhIII hydroxide species is monomerically (or highly) dispersed on the Al2O3 support. Rh(OH)x/Al2O3 acts as a reusable heterogeneous catalyst in water, rather than in an explosive, hazardous, and carcinogenic organic solvent, for the synthesis of primary amides from aldoximes or aldehydes by an efficient sequential process of dehydration and rehydration. The dehydrative condensation of aldehydes and hydroxylamine is also promoted by the Rh(OH)x/Al2O3 catalyst.
Analysis of individual‐ and school‐level clustering of power frequency magnetic fields
Authors: Lin I‐Fan , Li Chung‐Yi , Wang Jung‐Der
Published: June 2008

This study reports the continuous 8‐h monitoring of data on extremely low‐frequency magnetic fields (ELF‐MF) relating to 14 children and 35 teachers in 11 elementary schools in Northern Taiwan. It was anticipated that the subjects in two of these campuses would have elevated exposure to ELF‐MF as a result of their close proximity to high‐voltage (161 kilo‐Volt, kV) power lines. The results of our analysis reveal that in those schools with high‐voltage power lines running through the campuses, the mean ELF‐MF exposure level (0.38 ± 0.51 micro‐Tesla (µT), or 0.15, 0.25 and 0.44 µT at the respective 25th, 50th and 75th percentiles) was higher than the mean ELF‐MF exposure level for campuses situated far away from such high‐voltage power lines (0.14 ± 0.27 µT, or 0.04, 0.06 and 0.10 µT at the respective 25th, 50th and 75th percentiles). The multi‐level analytical technique, which takes individual measurements as the analytical unit, and which also takes into consideration the inter‐correlation between measurements from the same individual and/or campus, was also applied to the analysis of the data. We conclude that individual‐level and school‐level clustering of the measurements, both of which were discernible in this study, should be taken into consideration in any future analysis of data obtained from the continuous monitoring of exposure to ELF‐MF. Bioelectromagnetics 29:564–570, 2008. © 2008 Wiley‐Liss, Inc.
Structure, biological activity, and enzymatic transformation of fucoidans from the brown seaweeds
Authors: Kusaykin Mikhail , Bakunina Irina , Sova Victoria , Ermakova Svetlana , Kuznetsova Tatyana , Besednova Natalya , Zaporozhets Tatyana , Zvyagintseva Tatyana
Published: June 2008

Recent advances in the study of fucoidans, biologically active sulfated α‐L‐fucans of diverse structures and synthesized exclusively by marine organisms, are overviewed. Their structure, biological activity, the products of their enzymatic degradation and the different enzymes of degradation and modification are considered.
Development and application of an automated, low‐volume chromatography system for resin and condition screening
Authors: Teeters Mark , Bezila Daniel , Alred Patricia , Velayudhan Ajoy
Published: June 2008

A small‐volume chromatography system was developed for rapid resin and parameter screening and applied to the purification of a therapeutic monoclonal antibody from a key product‐related impurity. Accounting for constraints in peripheral volume, gradient formation, column integrity, and fraction collection in microtiter plates, the resulting system employed 2‐mL columns and was successfully integrated with plate‐based methods for rapid sample analysis (e. g., use of automated liquid handlers, plate readers, and HPLC). Several cation‐exchange chromatography resins were screened using automated programs and tailored gradients for the combination of a particular resin and a given antibody feedstock produced during Phase 1 development. Results from the tailored gradient runs were used to select a resin, and to arrive at efficient stepwise elution schedules for the chosen resin. By maintaining a constant residence time, final operating parameters were successfully scaled to representative bed heights and column diameters up to 2.6 cm (106 mL). This approach significantly improved throughput while reducing development time and material consumption.
Direct plant gene delivery with a poly(amidoamine) dendrimer
Authors: Pasupathy Karthikeyan , Lin Sijie , Hu Qian , Luo Hong , Ke Pu Chun
Published: June 2008

Plant gene delivery is challenging due to the presence of plant cell walls. Conventional means such as Agrobacterium infection, biolistic particle bombardment, electroporation, or polyethylene glycol attachment are often characterized by high cost, labor extensiveness, and a significant perturbation to the growth of cells. We have succeeded in delivering GFP‐encoding plasmid DNA to turfgrass cells using poly(amidoamine) dendrimers. Our new scheme utilizes the physiochemical properties as well as the nanosize of the poly(amidoamine) dendrimer for direct and noninvasive gene delivery. The GFP gene was expressed in the plant cells as observed by confocal fluorescence microscopy. The transfection efficiency may be further improved by optimizing the pH of the cell culture medium and the molar ratio of the dendrimer to DNA. The use of the current delivery system can be extended to virtually all plant species having successful regeneration systems in place.
Protozoan biomass relation to nutrient and chemical oxygen demand removal in activated sludge mixed liquor
Authors: Akpor Oghenerobor B. , Momba Maggy N. B. , Okonkwo Jonathan O.
Published: June 2008

The relationship between biomass concentration to nutrient and chemical oxygen demand (COD) removal in mixed liquor supplemented with sodium acetate was investigated, using three protozoan isolates and three different initial biomass concentrations (101, 102 and 103 cells/mL). The study was carried out in a shaking flask environment at a shaking speed of 100 rpm for 96 h at 25°C. Aliquot samples were taken periodically for the determination of phosphate, nitrate, COD and dissolved oxygen, using standard methods. The results revealed remarkable phosphate removal of 82–95% at biomass concentration of 103cells/mL. A high nitrate removal of over 87% was observed at all initial biomass concentration in mixed liquor. There was an observed COD increase of over 50% in mixed liquor in at the end of 96‐h incubation and this was irrespective of initial biomass concentration used for inoculation. The study shows the trend in nutrient and COD removal at different biomass concentrations of the test isolates in mixed liquor.
Exploitation of biological wastes for the production of value‐added products under solid‐state fermentation conditions
Authors: Rodríguez Couto Susana
Published: June 2008

Biological wastes contain several reusable substances of high value such as soluble sugars and fibre. Direct disposal of such wastes to soil or landfill causes serious environmental problems. Thus, the development of potential value‐added processes for these wastes is highly attractive. These biological wastes can be used as support‐substrates in solid‐state fermentation (SSF) to produce industrially relevant metabolites with great economical advantage. In addition, it is an environmentfriendly method of waste management. This paper reviews the reutilisation of biological wastes for the production of value‐added products using the SSF technique.
Expression of recombinant Hirudin in transgenic mice milk driven by the goat β‐casein promoter
Authors: Yen Chon‐Ho , Yang Chi‐Kai , Chen I‐Chung , Lin Yin‐Shen , Lin Chih‐Sheng , Chu Sen , Tu Ching‐Fu
Published: June 2008

Hirudin, isolated from the leechHirudo medicinalis,inhibits thrombin directly and several expression systems have been used to produce recombinant Hirudin (rHirudin) for pharmaceutical purposes. A DNA fragment containing the Hirudin coding sequence and goat β‐casein secretion signal was chemically synthesized in this study. The synthetic DNA then was further constructed into a goat β‐casein expression vector for mouse transgenesis. Four lines of transgenic mice were successfully developed and one line showed a meaningful anti‐thrombin activity of 40,000 anti‐thrombin units (ATU)/mL in their milk. In this animal line, Hirudin mRNA was found in samples of uterus and kidney with insignificant anti‐thrombin activity (≤ 280 ATU/g wet tissue); however, mammary glands showed a higher activity of 780 ATU/g wet tissue. Transgenic mice showed no evident physical abnormality. The purified rHirudin was further analyzed by amino acid analysis and was found to contain a tyrosineO‐sulfate residue that is absent in rHirudin expression either throughEscherichia colior yeast host systems. Experimental results demonstrated that the β‐casein‐promoted Hirudin transgene could be successfully expressed in a murine model and may be applicable to large mammals such as livestock for mass production of rHirudin for pharmaceuticals.
Fermentative butanol production by clostridia
Authors: Lee Sang Yup , Park Jin Hwan , Jang Seh Hee , Nielsen Lars K. , Kim Jaehyun , Jung Kwang S.
Published: June 2008

Butanol is an aliphatic saturated alcohol having the molecular formula of C4H9OH. Butanol can be used as an intermediate in chemical synthesis and as a solvent for a wide variety of chemical and textile industry applications. Moreover, butanol has been considered as a potential fuel or fuel additive. Biological production of butanol (with acetone and ethanol) was one of the largest industrial fermentation processes early in the 20th century. However, fermentative production of butanol had lost its competitiveness by 1960s due to increasing substrate costs and the advent of more efficient petrochemical processes. Recently, increasing demand for the use of renewable resources as feedstock for the production of chemicals combined with advances in biotechnology through omics, systems biology, metabolic engineering and innovative process developments is generating a renewed interest in fermentative butanol production. This article reviews biotechnological production of butanol by clostridia and some relevant fermentation and downstream processes. The strategies for strain improvement by metabolic engineering and further requirements to make fermentative butanol production a successful industrial process are also discussed. Biotechnol. Bioeng. 2008;101: 209–228. © 2008 Wiley Periodicals, Inc.
Thermodynamic Analysis of Nylon Nucleic Acids
Authors: Liu Yu , Wang Risheng , Ding Liang , Sha Ruojie , Lukeman Philip S. , Canary James W. , Seeman Nadrian C.
Published: June 2008

The stability and structure of nylon nucleic acid duplexes with complementary DNA and RNA strands was examined. Thermal denaturing studies of a series of oligonucleotides that contained nylon nucleic acids (1–5 amide linkages) revealed that the amide linkage significantly enhanced the binding affinity of nylon nucleic acids towards both complementary DNA (up to 26 °C increase in the thermal transition temperature (Tm) for five linkages) and RNA (around 15 °C increase in Tm for five linkages) compared with nonamide linked precursor strands. For both DNA and RNA complements, increasing derivatization decreased the melting temperatures of uncoupled molecules relative to unmodified strands; by contrast, increasing lengths of coupled copolymer raised Tm from less to slightly greater than Tm of unmodified strands. Thermodynamic data extracted from melting curves and CD spectra of nylon nucleic acid duplexes were consistent with loss of stability due to incorporation of pendent groups on the 2′‐position of ribose and recovery of stability upon linkage of the side chains.
Mesoporous Silicas by Self‐Assembly of Lipid Molecules: Ribbon, Hollow Sphere, and Chiral Materials
Authors: Jin Haiying , Qiu Huibin , Sakamoto Yasuhiro , Shu Peng , Terasaki Osamu , Che Shunai
Published: June 2008

Using lipids (N‐acyl amino acids) and 3‐aminopropyltriethoxysilane as structure‐ and co‐structure‐directing agents, mesoporous silicas with four different morphologies, that is, helical ribbon (HR), hollow sphere, circular disk, and helical hexagonal rod, were synthesized just by changing the synthesis temperature from 0 °C to 10, 15, or 20 °C. The structures were studied by electron microscopy. It was found that 1) the structures have double‐layer disordered mesopores in the HR, radially oriented mesopores in the hollow sphere, and highly ordered straight and chiral 2D‐hexagonal mesopores in the disklike structure and helical rod, respectively; 2) these four types of mesoporous silica were transformed from the flat bilayered lipid ribbon with a chain‐interdigitated layer phase through a solid–solid transformation for HR formation and a dissolving procedure transformation for the synthesis of the hollow sphere, circular disk, and twisted morphologies; 3) the mesoporous silica helical ribbon was exclusively right‐handed and the 2D‐hexagonal chiral mesoporous silica was excessively left‐handed when the L‐form N‐acyl amino acid was used as the lipid template; 4) the HR was formed only by the chiral lipid molecules, whereas the 2D‐hexagonal chiral mesoporous silicas were formed by chiral, achiral, and racemic lipids. Our findings give important information for the understanding of the formation of chiral materials at the molecular level and will facilitate a more efficient and systematic approach to the generation of rationalized chiral libraries.
Novel Biodegradable Adaptive Hydrogels: Controlled Synthesis and Full Characterization of the Amphiphilic Co‐Networks
Authors: Mespouille Laetitia , Coulembier Olivier , Paneva Dilyana , Degée Philippe , Rashkov Iliya , Dubois Philippe
Published: June 2008

Adaptive and amphiphilic poly(N,N‐dimethylamino‐2‐ethyl methacrylate‐graft‐poly[ε‐caprolactone]) co‐networks (netP(DMAEMA‐g‐PCL)) were synthesized from a combination of controlled polymerization techniques. Firstly, PCL cross‐linkers were produced by ring‐opening polymerization (ROP) of ε‐CL initiated by 1,4‐butane‐diol and catalyzed by tin(II) 2‐ethylhexanoate ([Sn(Oct)2]), followed by the quantitative esterification reaction of terminal hydroxyl end‐groups with methacrylic anhydride. Then, PCL cross‐linkers were copolymerized to DMAEMA monomers by atom‐transfer radical polymerization (ATRP) in THF at 60 °C using CuBr complexed by 1,1,4,7,10,10‐hexamethyltriethylenetetramine (HMTETA) and 2‐ethyl isobutyrylbromide (EiBBr) as catalytic complex and initiator, respectively. A comprehensive study of gel formation was carried out by employing dynamic light scattering (DLS) to determine the gel point as a function of several parameters and to characterize the viscous solutions obtained before the gel point was reached. The evolution of the mean diameters was compared to a model previously developed by Fukuda and these attest to the living formation of the polymer co‐network. Furthermore, we also demonstrated the reliability of ATRP for producing well‐defined and homogeneous polymer co‐networks by the smaller deviation from Flory's theory in terms of cross‐linking density. For sake of clarity, the impact of polymerization techniques over the final structure and, therefore, properties was highlighted by comparing two samples of similar composition, but that were produced by either ATRP or thermal‐initiated free‐radical polymerization (FRP).
Two‐Component Hydrogels Comprising Fatty Acids and Amines: Structure, Properties, and Application as a Template for the Synthesis of Metal Nanoparticles
Authors: Basit Hajra , Pal Asish , Sen Saikat , Bhattacharya Santanu
Published: June 2008

Stearic acid or eicosanoic acid mixed with di‐ or oligomeric amines in specific molar ratios form stable gels in water. The formation of such hydrogels depends on the hydrophobicity of the fatty acid, and also on the type of amine used. The gelation properties of these two‐component systems were investigated using electron microscopy, FTIR spectroscopy, 1H NMR spectroscopy, differential scanning calorimetry (DSC), and both single‐crystal and cast‐film X‐ray diffraction. Results of FTIR spectral analysis suggest salt formation during gelation. 1H NMR analysis of the gels indicates that the fatty acid chains are immobilized in the gel state and when the gel melts, these chains regain their mobility. Analysis of DSC data indicates that increase in the spacer length in the di‐/oligomeric amine lowers the gel‐melting temperature. Two of these gelator salts developed into crystals and structural details of such systems could be secured by single‐crystal X‐ray diffraction analysis. The structural information of the salts thus obtained was compared with the XRD data of the self‐supporting films of those gels. Such analyses provided pertinent structural insight into the supramolecular interactions that prevail within these gelator assemblies. Analysis of the crystal structure confirmed that multilayered lamellar aggregates exist in the gel and it also showed that the three‐dimensional ordering observed in the crystalline phase is retained in only one direction in the gel state. Finally, the hydrogel was used as a medium for the synthesis of silver nanoparticles. The nanoparticles were found to position themselves on the fibers and produced a long, ordered assembly of gel–nanoparticle composite.
Definition of Magneto‐Structural Correlations for the MnII Ion
Authors: Duboc Carole , Collomb Marie‐Noëlle , Pécaut Jacques , Deronzier Alain , Neese Frank
Published: June 2008

The electronic properties of the high spin mononuclear MnII complexes [Mn(tpa)(NCS)2] (1) (tpa=tris‐2‐picolylamine), [Mn(tBu3‐terpy)2](PF6)2 (2) (tBu3‐terpy=4,4′,4′′‐tri‐tert‐butyl‐2,2′:6′,2′′‐terpyridine) and [Mn(terpy)2](I)2 (3) (terpy=2,2′:6′,2′′‐terpyridine) with an N6 coordination sphere have been determined by multifrequency EPR spectroscopy. The X‐ray structures of 1⋅CH3CN and 2⋅C4H10O⋅0.5 C2H5OH⋅0.5 CH3OH reveal that the MnII ion lies at the center of a distorted octahedron. The D‐values of 1–3 all fall in the narrow range of 0.041 to 0.105 cm−1. The comparison of the results reported here and those found in the literature is consistent with the following observation: the D value is sensitive to the coordination number (6 or 5) of the MnII ion as long as the coordination sphere involves only nitrogen and/or oxygen based ligands. This magneto‐structural correlation has been analyzed in this work though DFT model calculations. The zero‐field splitting (zfs) parameters of 1–3 have been calculated and are in reasonable agreement with the experimental values. Hypothetical simplified models [Mn(NH3)x(OH2)y]2+ (x+y=5 or 6 and [Mn(NH3)5X]+ (X=OH, Cl)) have been constructed to investigate the origin of the zfs. This investigation reveals i) that D is sensitive to the coordination number (5 or 6) of the MnII ion, ii) for the five coordinate systems the major contribution to D is the spin‐orbit coupling part, iii) for the six coordinate systems the major contribution to D is the spin–spin interaction and iv) the deprotonation of a water ligand leads to an increase of D, consistent with the relative ligand fields of OH− versus H2O.
New Reactions of a Dibenzo[a,e]pentalene
Authors: Saito Masaichi , Nakamura Michio , Tajima Tomoyuki
Published: June 2008

Reduction of dibenzo[a,e]pentalene 3 (denoted as dibenzopentalene hereafter) with excess lithium gave dilithium dibenzopentalenide 1. Since oxidation of 1 with iodine gave 3, redox behavior between 1 and 3 is controllable and reversible. Reaction of 3 with methyllithium gave lithium 5‐methyldibenzopentalenide 5, the formation of which was evidenced by some trapping experiments and X‐ray crystallographic analysis. Reactions of 3 with halogens gave 5,10‐dihalodibenzopentalenes, 8 and 9. Some optical properties of novel dibenzopentalene derivatives are also demonstrated.
Anionic Cross‐Coupling Reaction of α‐Metallated Alkenyl Sulfoximines and Alkenyl Sulfoximines with Cuprates Featuring a 1,2‐Metal‐Ate Rearrangement of Sulfoximine‐Substituted Higher Order Alkenyl Cuprates and an α‐Metallation of Alkenyl Sulfoximines by Cuprates
Authors: Gais Hans‐Joachim , Rao C. Venkateshwar , Loo Ralf
Published: June 2008

(E)‐ and (Z)‐configured α‐lithioalkenyl sulfoximines, which are available through lithiation of the corresponding alkenyl sulfoximines, undergo a anionic cross‐coupling reaction (ACCR) with organocuprates with formation of the corresponding alkenyl cuprates and sulfinamide. The alkenyl cuprates can be trapped by electrophiles. The ACCR presumably proceeds via the formation of a higher‐order sulfoximine‐substituted alkenyl cuprate, which undergoes a 1,2‐metal‐ate rearrangement whereby the sulfoximine group acts as the nucleofuge. The parent (E)‐ and (Z)‐configured alkenyl sulfoximines suffer upon treatment with an organocuprate a deprotonation at the α‐position with formation of the corresponding α‐cuprioalkenyl sulfoximines. These derivatives also enter into a similar ACCR with organocuprates. The ACCR of sulfoximines substituted homoallylic alcohols allows a stereoselective access to enantio‐ and diastereopure substituted homoallylic alcohols.
Dendrimers and DNA: Combinations of Two Special Topologies for Nanomaterials and Biology
Authors: Caminade Anne‐Marie , Turrin Cédric‐Olivier , Majoral Jean‐Pierre
Published: June 2008

Interactions between two precisely defined three‐dimensional architectures (DNA and dendrimers) are described. Highly synergetic effects occur, as illustrated in two cases: dendrimers can be used as three‐dimensional linkers for oligonucleotides, affording highly sensitive microarrays (biochips), and positively charged dendrimers strongly interact with DNA, allowing penetration inside cells (genetic transfection).
Intramolecular Sensitization of Photocleavage of the Photolabile 2‐(2‐Nitrophenyl)propoxycarbonyl (NPPOC) Protecting Group: Photoproducts and Photokinetics of the Release of Nucleosides
Authors: Wöll Dominik , Smirnova Julia , Galetskaya Marina , Prykota Tamara , Bühler Jochen , Stengele Klaus‐Peter , Pfleiderer Wolfgang , Steiner Ulrich E.
Published: June 2008

Novel photolabile protecting groups based on the 2‐(2‐nitrophenyl)propoxycarbonyl (NPPOC) group with a covalently linked thioxanthone as an intramolecular triplet sensitizer exhibit significantly enhanced light sensitivity under continuous illumination. Herein we present a detailed study of the photokinetics and photoproducts of nucleosides caged with these new protecting groups. Relative to the parent NPPOC group, the light sensitivity of the new photolabile protecting groups is enhanced by up to a factor of 21 at 366 nm and is still quite high at 405 nm, the wavelength at which the sensitivity of the parent compound is practically zero. A new pathway for deprotection of the NPPOC group proceeding through a nitroso benzylalcohol intermediate has been discovered to complement the main mechanism, which involves β elimination. Under standard conditions of lithographic DNA‐chip synthesis, some of the new compounds, while maintaining the same chip quality, react ten times faster than the unmodified NPPOC‐protected nucleosides.