bluuebunny/crossref_metadata_2025 huggingface dataset:
Simulated Moving Bed Chromatography: From Concept to Proof‐of‐Concept
Authors: Sá Gomes P. , Rodrigues A. E.
Published: December 2011

This work presents a comprehensive insight about simulated moving bed (SMB) technology, from concept to unit operation and process demonstration. A particular relevance is given to SMB nonconventional modes of operation, modeling, and design of SMB‐based separations as well as to the construction and operation of SMB units. A conventional separation of a racemic mixture of (S,R)‐α‐tetralol by means of the FlexSMB‐LSRE® unit is addressed to better exemplify a state‐of‐the‐art SMB lab‐scale process development and demonstration.
Do Glycosyl Sulfonium Ions Engage in Neighbouring‐Group Participation? A Study of Oxathiane Glycosyl Donors and the Basis for their Stereoselectivity
Authors: Fascione Martin A. , Kilner Colin A. , Leach Andrew G. , Turnbull W. Bruce
Published: December 2011

Neighbouring‐group participation has long been used to control the synthesis of 1,2‐trans‐glycosides. More recently there has been a growing interest in the development of similar strategies for the synthesis of 1,2‐cis‐glycosides, in particular the use of auxiliary groups that generate sulfonium ion intermediates. However, there has been some debate over the role of sulfonium ion intermediates in these reactions: do sulfonium ions actually engage in neighbouring‐group participation, or are they a resting state of the system prior to reaction through an oxacarbenium ion intermediate? Herein, we describe the reactivities and stereoselectivities of a family of bicyclic thioglycosides in which an oxathiane ring is fused to the sugar to form a trans‐decalin‐like structure. A methyl sulfonium ion derived from one such glycosyl donor is so stable that it can be crystallised from ethanol, yet it reacts with complete stereoselectivity at high temperature. The importance of a ketal group in the oxathiane ring for maintaining this high stereoselectivity is investigated using a combination of experiment and ab initio calculations. The data are discussed in terms of SN1 and SN2 type mechanisms. Trends in stereoselectivity across a series of compounds are more consistent with selective addition to oxacarbenium ions rather than a shift between SN1 and SN2 mechanisms.
Intramolecular Domino Electrophilic and Thermal Cyclization of peri‐Ethynylene Naphthalene Oligomers
Authors: Huang Xiaobo , Zeng Lintao , Zeng Zebing , Wu Jishan
Published: December 2011

The intramolecular electrophilic or thermal cyclization of arylene ethynylene precursors recently became a powerful method for the synthesis of new polycyclic aromatic hydrocarbons (PAHs). In this work, we investigated in detail the synthesis and intramolecular cyclization reaction of a series of peri‐ethynylene naphthalene oligomers in which the ethynylene units are fixed in close proximity within the naphthalene framework. The high reactivity of these precursors led to simultaneous thermal cyclization reactions, even during their syntheses. Electrophilic cyclizations with iodine were also undertaken. Several new PAHs containing five‐membered rings, for example, indeno[2,1‐a]phenalene, acenaphtho[1,2‐a]pyrene, and benzo‐ or naphtho‐annulated fluoranthene derivatives, were synthesized and their structures were unambiguously determined by X‐ray crystallographic analysis. Plausible mechanisms were proposed and it was demonstrated that oligomers most probably underwent intramolecular domino cyclization via either radical or cationic intermediates. The photophysical and electrochemical properties of these new PAHs were investigated and some of them displayed amphoteric redox behavior, due to the existence of five‐membered rings.
Stable N‐Heterocyclic Carbene (NHC)–Palladium(0) Complexes as Active Catalysts for Olefin Cyclopropanation Reactions with Ethyl Diazoacetate
Authors: Martín Carmen , Molina Francisco , Alvarez Eleuterio , Belderrain Tomás R.
Published: December 2011

The Pd0 complexes [(NHC)PdLn] (NHC=N‐heterocyclic carbene ligand; L=styrene for n=2 or PR3 for n=1) efficiently catalyse olefin cyclopropanation by using ethyl diazoacetate (EDA) as the carbene source with activities that improve on previously described catalytic systems based on this metal. Mechanistic studies have shown that all of these catalyst precursors deliver the same catalytic species in solution, that is, [(IPr)Pd(sty)], a 14e− unsaturated intermediate that further reacts with EDA to afford [(IPr)Pd(CHCO2Et)(sty)], from which the cyclopropane is formed.
Fully developed mixed convection of a binary fluid in a vertical porous channel
Authors: Alloui Z. , Vasseur P.
Published: December 2011

This paper reports an analytical and numerical study of mixed convection heat and mass transfer of a binary fluid in a vertical parallel plate channel filled with a porous medium. The thermal conditions applied on the walls of the system are uniform heat fluxes. Both the cases of double‐diffusion and Soret‐induced convection are considered. The governing equations for the porous medium rely on Darcy's model. The governing parameters for the problem are the Rayleigh number, Ra, Peclet number, Pe, Lewis number, Le, buoyancy ratio, φ, aspect ratio of the channel $A = L'/H'$ and the constant a (a = 0 for double diffusive convection and a = 1 for Soret induced convection). The resulting problem, in the limit of fully developed mixed convection, is solved analytically in closed form. A numerical solution of the full governing equations is demonstrated to be in good agreement with the analytical model. The temperature and velocity fields and the Nusselt and Sherwood numbers are obtained in terms of the governing parameters. The possible existence of reversed flows in the channel is discussed. © 2011 Canadian Society for Chemical Engineering
The isolation of poly(3‐hydroxybutyrate) from recombinant Escherichia coli XL1‐blue using the digestion method
Authors: Peng Yu‐Chiang , Lo Chi‐Wei , Wu Ho‐Shing
Published: December 2011

This study examines the isolation of poly(3‐hydroxybutyrate) (PHB) from recombinant Escherichia coli XL1‐blue pBHB2 OLD‐2 harbouring the PHB biosynthesis gene. Six types of commercial surfactants (Emal 10P, Emal AD‐25, Emal S PASTE, Neopelex S‐S, Triton X‐100 and cetyl trimethyl ammonium bromide (CTAB)) were screened for PHB isolation by solubilising non‐polymer cellular material (NPCM) in the cell. Emal 10P, Emal AD‐25, Emal S PASTE and Triton X‐100 are suitable surfactants for PHB isolation. Factors such as the reaction temperature, reaction time, ratio of NPCM/surfactant and pH were investigated to achieve optimum conditions. For 80% of the PHB content in dry cells, the purity and recovery of the obtained PHB was 98% and 99% when 0.67 of NPCM/Emal S PASTE was used at 70°C for 30 min. The cost of the used surfactant is below 0.5 USD/kg (PHB). The pretreatment and multistage digestion method must be combined when the PHB content is lower than 80%. © 2011 Canadian Society for Chemical Engineering
MicroRNA‐200b reverses chemoresistance of docetaxel‐resistant human lung adenocarcinoma cells by targeting E2F3
Authors: Feng Bing , Wang Rui , Song Hai‐Zhu , Chen Long‐Bang
Published: December 2011

BACKGROUND:

MicroRNAs (miRNAs) have been identified as important posttranscriptional regulators involved in various biological and pathological processes of cells, but their association with tumor chemoresistance has not been fully understood.

METHODS:

We detected miRNA‐200b (miR‐200b) expression in different lung adenocarcinoma cell lines and then focused on its roles in regulation of docetaxel chemoresistance. We also identified E2F3 as a novel target of miR‐200b.

RESULTS:

Based on miRNA microarray data, miR‐200b was identified as the most down‐regulated miRNA in docetaxel‐resistant SPC‐A1/DTX cells compared with parental SPC‐A1 cells. Ectopic miR‐200b expression reversed docetaxel chemoresistance of lung adenocarcinoma cells through cell proliferation inhibition, apoptosis enhancement, and G2/M cell cycle arrest. In a nude mouse xenograft model, up‐regulation of miR‐200b significantly enhanced response of SPC‐A1/DTX cells to docetaxel. Luciferase reporters containing the 3′ untranslated region sequence of E2F3 messenger RNA were used to demonstrate that miR‐200b could directly target E2F3. Small interfering RNA–mediated E2F3 knockdown revealed similar effects as that of ectopic miR‐200b expression. Decreased miR‐200b expression was also detected in tumor tissues sampled from lung adenocarcinoma patients treated with docetaxel‐based chemotherapy and was proved to be correlated with high expression of E2F3, decreased sensitivity to docetaxel, and poor prognosis.

CONCLUSIONS:

Our results suggest that down‐regulation of miR‐200b could lead to E2F3 overexpression and in turn contribute to chemoresistance of lung adenocarcinoma cells to docetaxel. Cancer 2011. © 2011 American Cancer Society.
Prospective assessment of outcomes in 411 patients treated with hyperbaric oxygen for chronic radiation tissue injury
Authors: Hampson Neil B. , Holm James R. , Wreford‐Brown Claude E. , Feldmeier John
Published: December 2011

BACKGROUND:

Although hyperbaric oxygen is used to treat chronic radiation tissue injury, clinical evidence supporting its efficacy has been limited to date. The authors report prospectively collected patient outcomes from a single center's large experience using hyperbaric oxygen to treat chronic radiation injury.

METHODS:

Since 2002, patient outcomes at the conclusion of a course of hyperbaric oxygen treatment for chronic radiation tissue injury at Virginia Mason Medical Center in Seattle have been graded by a board‐certified hyperbaric physician and prospectively recorded. From 2002 to 2010, a total of 525 patients received treatment for 1 of 6 forms of radionecrosis analyzed. After excluding 114 patients for incomplete records or treatment courses or for previous receipt of hyperbaric oxygen therapy, records of 411 patients were retrospectively reviewed in 2010, and outcomes were regraded by a second board‐certified physician. A positive clinical response was defined as an outcome graded as either “resolved” (90%‐100% improved) or “significantly improved” (50%‐89% improved).

RESULTS:

A positive outcome from hyperbaric treatment occurred in 94% of patients with osteoradionecrosis of the jaw (n = 43), 76% of patients with cutaneous radionecrosis that caused open wounds (n = 58), 82% of patients with laryngeal radionecrosis (n = 27), 89% of patients with radiation cystitis (n = 44), 63% of patients with gastrointestinal radionecrosis (n = 73), and 100% of patients who were treated in conjunction with oral surgery in a previously irradiated jaw (n = 166).

CONCLUSIONS:

The outcomes of 411 patients collected prospectively over 8 years strongly supported the efficacy of hyperbaric oxygen treatment for the 6 conditions evaluated. The response rates previously reported in numerous small series were supported by the responses achieved in this large, single‐center experience. Cancer 2012. © 2011 American Cancer Society.
Improved survival for BRCA2‐associated serous ovarian cancer compared with both BRCA‐negative and BRCA1‐associated serous ovarian cancer
Authors: Hyman David M. , Zhou Qin , Iasonos Alexia , Grisham Rachel N. , Arnold Angela G. , Phillips Mary F. , Bhatia Jasmine , Levine Douglas A. , Aghajanian Carol , Offit Kenneth , Barakat Richard R. , Spriggs David R. , Kauff Noah D.
Published: December 2011

BACKGROUND:

Multiple observational studies have suggested that breast cancer gene (BRCA)‐associated ovarian cancers have improved survival compared with BRCA‐negative ovarian cancers. However, most of those studies combined BRCA1 and BRCA2 patients or evaluated only BRCA1 patients. The objective of the current study was to examine whether BRCA1‐associated and BRCA2‐associated ovarian cancers were associated with different outcomes.

METHODS:

This was a single‐institution, retrospective analysis of patients who had a new diagnosis of histologically confirmed stage III or IV serous ovarian, fallopian tube, or primary peritoneal cancer between January 1, 1996 and February 1, 2011 and who underwent BRCA mutation testing on 1 of 2 institutional review board‐approved follow‐up studies. Patients who had been tested for BRCA mutations beyond 24 months of diagnosis were excluded from analysis to minimize selection bias from including patients who were referred for genetic testing because of long survival.

RESULTS:

Data from 190 patients (143 BRCA‐negative patients, 30 BRCA1‐positive patients, and 17 BRCA2‐positive patients) were analyzed. During the study period, 73 deaths were observed (60 BRCA‐negative patients, 10 BRCA1‐positive patients, 3 BRCA2‐positive patients). The median follow‐up for the remaining 117 survivors was 2.5 years. At 3 years, 69.4%, 90.7%, and 100% of BRCA‐negative patients, BRCA1‐positive patients, and BRCA2‐positive patients were alive, respectively. On univariate analysis, age, BRCA2 mutations, debulking status, and type of first‐line therapy (intravenous or intraperitoneal) were significant predictors of overall survival. On multivariate analysis, BRCA2 mutations (hazard ratio, 0.20; 95% confidence interval, 0.06‐0.65; P = .007), but not BRCA1 mutations (hazard ratio, 0.70; 95% confidence interval, 0.36‐1.38; P = .31), predicted for improved overall survival compared with BRCA‐negative patients. When carriers of BRCA2 mutations were directly compared with carriers of BRCA1 mutations, BRCA2 mutations appeared to confer improved overall survival (hazard ratio, 0.29; 95% confidence interval, 0.08‐1.05; P = .060), although this finding did not reach significance.

CONCLUSIONS:

The current data suggests that BRCA2 mutations confer an overall survival advantage compared with either being BRCA‐negative or having a BRCA1 mutation in high‐grade serous ovarian cancer. This finding may have important implications for clinical trial design. Cancer 2012. © 2011 American Cancer Society.
A phase 1 dose‐escalation study of ARRY‐520, a kinesin spindle protein inhibitor, in patients with advanced myeloid leukemias
Authors: Khoury Hanna Jean , Garcia‐Manero Guillermo , Borthakur Gautam , Kadia Tapan , Foudray Maria Cielo , Arellano Martha , Langston Amelia , Bethelmie‐Bryan Beverly , Rush Selena , Litwiler Kevin , Karan Sharon , Simmons Heidi , Marcus Adam I. , Ptaszynski Mieke , Kantarjian Hagop
Published: December 2011

BACKGROUND:

ARRY‐520 selectively inhibits the mitotic kinesin spindle protein (KSP), which leads to abnormal monopolar spindle formation and apoptosis.

METHODS:

A phase 1 trial was conducted to establish the safety and the maximum tolerated dose (MTD) of ARRY‐520 given as a 1‐hour infusion in either a single dose or on a day 1, 3, and 5 divided‐dose schedule per cycle in patients with advanced or refractory myeloid leukemias. Additional objectives were to characterize pharmacokinetics, assess preliminary clinical activity, and explore biomarkers of KSP inhibition with ARRY‐520. A total of 36 patients with acute myelogenous leukemia (n = 34) or myelodysplastic syndromes (n = 2) with a median age of 66 years (range, 21‐88 years) were enrolled: 15 in the single‐dose schedule (dose levels: 2.5, 3.75, 4.5, and 5.6 mg/m2) and 21 in the divided‐dose schedule (dose levels: 0.8, 1.2, 1.5, and 1.8 mg/m2/day).

RESULTS:

The MTD was 4.5 mg/m2 total dose per cycle for both dose schedules. Dose‐limiting toxicities included mucositis, exfoliative rash, hand‐foot syndrome, and hyperbilirubinemia. Grades 3 or 4 reversible drug‐related myelosuppression were observed in 33 of 36 patients. Plasma pharmacokinetic analyses revealed low clearance of ARRY‐520 (∼3 L/hour), a volume of distribution of ∼450 L, and a median terminal half‐life of >90 hours. Monopolar spindles were observed in blood mononuclear cells, through use of 4′,6‐diamidino‐2‐phenylindole nucleic acid stain and antitubulin antibodies.

CONCLUSIONS:

On the basis of the relative lack of clinical activity, further development of ARRY‐520 as an antileukemic agent was halted. (Clinicaltrials.gov identifier NCT00637052). Cancer 2012;3556–3564. © 2011 American Cancer Society.
Comparison between Two Anionic Reverse Micelle Interfaces: The Role of Water–Surfactant Interactions in Interfacial Properties
Authors: Quintana Silvina S. , Falcone R. Dario , Silber Juana J. , Correa N. Mariano
Published: December 2011

The water/sodium bis(2‐ethylhexyl) phosphate (NaDEHP) reverse micelle (RM) system is revisited by using, for the first time, molecular probes to investigate interface properties. The solvatochromic behavior of 1‐methyl‐8‐oxyquinolinium betaine (QB) and 6‐propionyl‐2‐(N,N‐dimethyl)aminonaphthalene (PRODAN) in the water/NaDEHP/toluene system is studied, and the results are compared with those obtained in water/sodium 1,4‐bis(2‐ethylhexyl) sulfosuccinate (AOT)/toluene RM media. The results demonstrate that the micropolarity, microviscosity, interfacial water structure, molecular probe partition, and intramolecular electron‐transfer processes are dramatically altered for NaDEHP RM interfaces in comparison to the AOT systems. Because of organic nonpolar solvent penetration into the interface, NaDEHP RM media offer an interface with lower micropolarity and microviscosity than AOT media. Also, the interfacial water in the NaDEHP system shows enhanced water–water hydrogen‐bond interaction in comparison with bulk water. The AOT RM interface represents a unique environment for PRODAN to undergo dual emission.
Effect of copper (II) ion against elongation behavior of amyloid β fibrils on liposome membranes
Authors: Shimanouchi T. , Onishi R. , Kitaura N. , Umakoshi H. , Kuboi R.
Published: December 2011

The fibril growth behavior of amyloid β protein (Aβ) on cell membranes is relating to the progression of Alzheimer's disease. This growth behavior of Aβ fibrils is sensitively affected by the metal ions, neurotransmitters, or bioreactive substrate. The inhibitory effect of those materials was quantitatively estimated from the viewpoints of “crystal growth”. In a bulk aqueous solution, copper (II) ion showed the strong inhibitory effect on the growth of Aβ fibrils. Meanwhile, the addition of a closed‐phospholipid bilayer membrane (liposome) could reduce the above inhibitory effect of copper (II) ion. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Chiral symmetry breaking in unstirred crystallization
Authors: Szurgot M.
Published: December 2011

Statistics of nucleation of chiral forms of sodium bromate from unstirred aqueous solutions was studied. It was established that bimodal, trimodal and unimodal distributions of enantiomers are obtained in unstirred crystallization. It was also found out that probabilities of the creation of L or D crystals and racemates R, as well as the presence of D, L, and R peaks in distributions depend on crystallizer size, supersaturation and temperature. Nucleation at low supersaturations in small, closed crystallizers leads to the formation of pure enantiomers, and to bimodal distributions with D and L peaks at any temperature. At high supersaturations in large, open crystallizers the formation of racemates and unimodal distributions with racemate R peaks results. In open crystallizers at the lowest temperatures and at the highest temperatures used in crystallization from aqueous solution racemates of sodium bromate are preferentially formed, but in a wide range of intermediate‐temperatures apart from racemates, pure enantiomers are efficiently formed which leads to trimodal distributions. The spontaneous formation of pure enantiomers in crystallization from unstirred, unseeded solutions is caused by the chiral symmetry breaking phenomenon, the same as that discovered in stirred crystallization. The conservation of chiral symmetry is, in unstirred crystallization, one of the two possibilities, and the other one is the breakage of symmetry. Both of them occur in nature. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Prilezhaev Dihydroxylation of Olefins in a Continuous Flow Process
Authors: van den Broek Bas A. M. W. , Becker René , Kössl Florian , Delville Mariëlle M. E. , Nieuwland Pieter J. , Koch Kaspar , Rutjes Floris P. J. T.
Published: December 2011

Epoxidation of both terminal and non‐terminal olefins with peroxy acids is a well‐established and powerful tool in a wide variety of chemical processes. In an additional step, the epoxide can be readily converted into the corresponding trans‐diol. Batch‐wise scale‐up, however, is often troublesome because of the thermal instability and explosive character of the peroxy acids involved. This article describes the design and semi‐automated optimization of a continuous flow process and subsequent scale‐up to preparative production volumes in an intrinsically safe manner.
Phenotypic covariance structure and its divergence for acoustic mate attraction signals among four cricket species
Authors: Bertram Susan M. , Fitzsimmons Lauren P. , McAuley Emily M. , Rundle Howard D. , Gorelick Root
Published: December 2011

The phenotypic variance–covariance matrix (P) describes the multivariate distribution of a population in phenotypic space, providing direct insight into the appropriateness of measured traits within the context of multicollinearity (i.e., do they describe any significant variance that is independent of other traits), and whether trait covariances restrict the combinations of phenotypes available to selection. Given the importance of P, it is therefore surprising that phenotypic covariances are seldom jointly analyzed and that the dimensionality of P has rarely been investigated in a rigorous statistical framework. Here, we used a repeated measures approach to quantify P separately for populations of four cricket species using seven acoustic signaling traits thought to enhance mate attraction. P was of full or almost full dimensionality in all four species, indicating that all traits conveyed some information that was independent of the other traits, and that phenotypic trait covariances do not constrain the combinations of signaling traits available to selection. P also differed significantly among species, although the dominant axis of phenotypic variation (p
max) was largely shared among three of the species (Acheta domesticus, Gryllus assimilis, G. texensis), but different in the fourth (G. veletis). In G. veletis and A. domesticus, but not G. assimilis and G. texensis, p
max was correlated with body size, while p
max was not correlated with residual mass (a condition measure) in any of the species. This study reveals the importance of jointly analyzing phenotypic traits.
Northern refugia and recent expansion in the North Sea: the case of the wrasse Symphodus melops (Linnaeus, 1758)
Authors: Robalo Joana I. , Castilho Rita , Francisco Sara M. , Almada Frederico , Knutsen Halvor , Jorde Per E. , Pereira Ana M. , Almada Vitor C.
Published: December 2011

Pleistocene climate changes have imposed extreme conditions to intertidal rocky marine communities, forcing many species to significant range shifts in their geographical distributions. Phylogeographic analyses based on both mitochondrial and nuclear genetic markers provide a useful approach to unravel phylogeographic patterns and processes of species after this time period, to gain general knowledge of how climatic changes affect shifts in species distributions. We analyzed these patterns on the corkwing wrasse (Symphodus melops, Labridae), a rocky shore species inhabiting North Sea waters and temperate northeastern Atlantic Ocean from Norway to Morocco including the Azores, using a fragment of the mitochondrial control region and the first intron of the nuclear S7 ribosomal protein gene. We found that S. melops shows a clear differentiation between the Atlantic and the Scandinavian populations and a sharp contrast in the genetic diversity, high in the south and low in the north. Within each of these main geographic areas there is little or no genetic differentiation. The species may have persisted throughout the last glacial maximum in the southern areas as paleotemperatures were not lower than they are today in North Scandinavia. The North Sea recolonization most likely took place during the current interglacial and is dominated by a haplotype absent from the south of the study area, but present in Plymouth and Belfast. The possibility of a glacial refugium in or near the English Channel is discussed.
Synthesis of Triazole‐Epothilones by Using Cu2O Nanoparticles to Catalyze 1,3‐Dipolar Cycloaddition
Authors: Duan Xiyan , Zhang Yan , Ding Yahui , Lin Jianping , Kong Xianglei , Zhang Quan , Dong Changming , Luo Guoan , Chen Yue
Published: December 2011

We report the total synthesis of a triazole‐epothilone analogue 1. The key step to generate the macrocyclic ring and the triazole ring was to apply Cu2O nanoparticles (Cu2O‐NPs) to catalyze the 1,3‐dipolar cycloaddition. The conformation of 1 and its bioactivity in MCF cancer cell lines were investigated.
A Cyclobutene‐1,2‐bis(imidazolium) Salt as Preligand for Palladium‐Catalyzed Cross‐Coupling Reactions: Properties and Applications
Authors: Rahimi Alireza , Pápai Imre , Madarász Ádám , Gjikaj Mimoza , Namyslo Jan C. , Schmidt Andreas
Published: December 2011

Spectroscopic investigations and the results of calculations on the title bis‐imidazolium salt, its mono‐ and bis‐carbenes, and its interactions with palladium are presented. In addition, we report on the scope and limitations of metal‐catalyzed cross‐coupling reactions performed with the title bis‐imidazolium salt. The salt proved to be an efficient ligand precursor in room‐temperature Suzuki–Miyaura reactions, C–C couplings with sterically extremely hindered biaryls,selective thiophene arylations, and couplings with vinylic chlorides.
Recent advances in single‐molecule detection on micro‐ and nano‐fluidic devices
Authors: Liu Chang , Qu Yueyang , Luo Yong , Fang Ning
Published: December 2011

Single‐molecule detection (SMD) allows static and dynamic heterogeneities from seemingly equal molecules to be revealed in the studies of molecular structures and intra‐ and inter‐molecular interactions. Micro‐ and nanometer‐sized structures, including channels, chambers, droplets, etc., in microfluidic and nanofluidic devices allow diffusion‐controlled reactions to be accelerated and provide high signal‐to‐noise ratio for optical signals. These two active research frontiers have been combined to provide unprecedented capabilities for chemical and biological studies. This review summarizes the advances of SMD performed on microfluidic and nanofluidic devices published in the past five years. The latest developments on optical SMD methods, microfluidic SMD platforms, and on‐chip SMD applications are discussed herein and future development directions are also envisioned.
Microfluidic chip‐capillary electrophoresis with dynamic multi‐segment standard addition for rapidly identifying nephrolithiasis markers in urine
Authors: Guo Wen Peng , Fung Ying Sing
Published: December 2011

A microchip‐CE device was fabricated for bed‐side monitoring of nephrolithiasis biomarkers in urine by incorporating on‐chip continuous passive mixing and standard addition to reduce sample matrix interference, increase sample throughput and eliminate accessories for active mixing. Under optimized conditions with buffer containing 20 mM borate and 0.5 mM CTAB at pH 10.3, sample and standards injected electrokinetically at −350 V for 10 s for online mixing in a Y‐merging flow microchannel prior to CE separation and UV detection at 210 nm, both inhibitors (citrate, CA) and promoters (oxalate, OA and uric acid, UA) for nephrolithiasis can be separated and determined in human urine in a single run completed within 10 min after a simple 50‐fold sample dilution and filtering. Satisfactory working ranges from 0.13–40, 0.25–40 and 0.025–40 mM, LOD 2.6, 6.1 and 0.7 μM, repeatability (%RSD, n=5) for migration time 1.40, 1.43, 0.47 and peak area 4.46, 6.10, 1.98, respectively, for CA, OA and UA are obtained for urine samples. The use of on‐chip standard addition is shown to improve repeatability of the migration time, assist the identification of nephrolithiasis markers from difficult samples with noisy baseline and enlarge the working range for nephrolithiasis marker determination. The device developed can be used for both routine and emergency monitoring to deliver results on demand for bedside monitoring and public health protection. It provides an early detection of nephrolithiasis to enable timely treatments, ease anxiety of parents for neonates consuming suspected contaminated food, and quick results for patients in a critical condition.
PDMS microchip coated with polydopamine/gold nanoparticles hybrid for efficient electrophoresis separation of amino acids
Authors: Liang Ru‐Ping , Meng Xiang‐Ying , Liu Chun‐Ming , Qiu Jian‐Ding
Published: December 2011

In this paper, a novel, simple, economical and environmentally friendly method based on in situ chemically induced synthesis strategy was designed and developed for the modification of a poly(dimethylsiloxane) (PDMS) microchip channel with polydopamine/gold nanoparticles (PDA/Au NPs) to create a hydrophilic and biofouling resistant surface. Dopamine as a reductant and a monomer, and HAuCl4 as an oxidant to trigger dopamine polymerization and the source of metallic nanoparticles, were filled into the PDMS microchannel to yield in situ a well‐distributed and robust PDA/Au NP coating. Au NPs were highly and uniformly dispersed in/on the PDA matrix with a narrow size distribution, as verified by scanning electron microscopy and UV‐vis spectra. Compared with the native PDMS microchannel, the modified surfaces exhibited much better wettability, high stability and suppressed electroosmotic mobility, and less nonspecific adsorption towards biomolecules. The water contact angle and EOF of PDA/Au NP‐coated PDMS microchip were measured to be 13° and 4.17×10−4 cm2/V s, compared to those of 111° and 5.33×10−4 cm2/V s from the native one, respectively. Fast and efficient separations of five amino acids such as arginine, proline, histidine, valine and threonine suggested greatly improved electrophoretic performance of the PDA/Au NP‐functionalized PDMS microchips. This one‐step procedure offers an effective approach for a biomimetic surface design on microfluidic chips, which is promising in high‐throughput and complex biological analysis.
Influence of moisture on the availability and persistence of clotrimazole and fluconazole in sludge-amended soil
Authors: García-Valcárcel Ana I. , Tadeo José L.
Published: December 2011

Applying sewage sludge to soil is a common practice in many parts of the world. Thus, pharmaceutical compounds, such as azoles, can be released into the environment after sludge is applied to soil. To understand the fate of clotrimazole and fluconazole (pharmaceuticals used as antifungals in humans) in soil after its amendment with sludge, a reliable and sensitive method has been developed to determine these compounds in the solid and aqueous phases of soil. Desorption of clotrimazole from soil amended with sludge was negligible, whereas a rapid desorption of fluconazole was observed. Dissipation rates of these azoles were determined in amended soil incubated at 25°C with moisture contents ranging from 4.5 to 20%. Clotrimazole was more persistent than fluconazole in dry soil, whereas the contrary occurred in wet soil. Partitioning soil:soil solution of these azoles varied with time and moisture contents. Clotrimazole was found in soil with negligible amounts in soil solution, whereas fluconazole was approximately partitioned 50:50 during the assay time (60 d) at any soil moisture content. Occasional rainfall coupled with a relatively low binding soil capacity can result in the contamination of surface and groundwaters by fluconazole, whereas clotrimazole will remain in the soil. Environ. Toxicol. Chem. 2012;31:501–507. © 2011 SETAC
Stability of leaf form and size during specimen preparation of herbarium specimens
Authors: Volkova Polina A. , Kasatskaya Sof'ya A. , Boiko Anna A. , Shipunov Alexey B.
Published: December 2011

It is common to draw taxonomic conclusions from the analysis of herbarium material and then apply them to living, fresh material. However, some widely used morphological characters are changed during the preparation of specimens and therefore the applicability of morphometric data obtained from the measurement of dried plants is not universal. We tried to estimate quantatively how different leaf characters change during drying. Fresh and dried leaves of ten plant species were measured and scanned to determine how the stability of commonly used absolute (e.g., leaf length) characters, relative characters (e.g., relative position of maximal width) and leaf contour. For the latter, we employed landmark‐based thin plate spline (TPS) analysis. We found that all absolute sizes differed significantly after drying (typically decrease original size 0.9–0.8 times), whereas leaf shape did not differ significantly between fresh and dried leaves of most species. Relative characters were more stable then absolute ones but less stable than a form as a whole. We argue that it is essential to provide measures, contours and/or photographs of fresh leaves together with herbarium material, all the more so because in two cases (20%) leaf contour also significantly changed after drying (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Neubau der Niedernfelder Brücken – Optimierte Rohrpfahlgründungen und ihre Tragfähigkeitsanalyse im Rahmen der Auswertung von dynamischen Probebelastungen
Authors: Höhmann Sebastian , Schau Dieter , Vater Christoph
Published: December 2011

Gründungen mittels gerammter Stahlrohrpfähle werden aufgrund ihrer hohen Tragfähig‐und Wirtschaftlichkeit vielfach eingesetzt. Jedoch ist das Tragverhalten dieses Pfahltyps, trotz zahlreicher Forschungsarbeiten und langjähriger Erfahrungen, noch nicht eindeutig geklärt. Im Rahmen des Neubaus der Niedernfelder Brücken im Hamburger Hafen konnten umfangreiche Untersuchungen an verstärkten und unverstärkten Stahlrohrpfählen durchgeführt werden. Die dadurch gewonnenen Erkenntnisse, in Verknüpfung mit Erfahrungen aus anderen Bauvorhaben, werden im Folgenden kurz vorgestellt.

Construction of the new “Niedernfelder Brücken” – Optimized tubular pile foundations and their bearing capacity, analyzed by dynamic pile load tests. Due to their high bearing capacity, their economic efficiency and their flexible operation conditions driven open ended piles are a commonly used foundation type. Notwithstanding a wide experience regarding this type of pile, the bearing behavior is not explicitly known. During the construction of the bridges “Niedernfelder Brücken” in the port of Hamburg extensive dynamic pile load tests were carried out at open ended piles with and without reinforcement. The resulting data and experiences gained in this project will be summarized in this paper.
DGGT‐Mitteilungen geotechnik 4/2011
Authors: Laackmann Kirsten
Published: December 2011

12th Baltic Sea Geotechnical Conference 2012 in Rostock

32. Baugrundtagung 2012 in Mainz

10. ICG und 33. Baugrundtagung 2014 in Berlin

Exkursionen zu Baustellen der Außerordentlichen Mitglieder

HTG‐DGGT‐DVWG‐Veranstaltung über Projekt “JadeWeserPort”

Initiative Praxisgerechte Regelwerke im Bauwesen – Projektgruppe 6 hat ihre Arbeit aufgenommen

International Society for Soil Mechanics and Geotechnical Engineering

International Society for Rock Mechanics

International Geosynthetics Society

Neuer Arbeitskreis “Forschung in der Geotechnik”

Fachsektion Felsmechanik

DGGT‐Geschäftsstelle
Associations among parenting experiences during childhood and adolescence, hypothalamus‐pituitary‐adrenal axis hypoactivity, and hippocampal gray matter volume reduction in young adults
Authors: Narita Kosuke , Fujihara Kazuyuki , Takei Yuichi , Suda Masashi , Aoyama Yoshiyuki , Uehara Toru , Majima Takehiko , Kosaka Hirotaka , Amanuma Makoto , Fukuda Masato , Mikuni Masahiko
Published: December 2011

Recent human studies have indicated that adverse parenting experiences during childhood and adolescence are associated with adulthood hypothalamus‐pituitary‐adrenal (HPA) axis hypoactivity. Chronic HPA axis hypoactivity inhibits hippocampal gray matter (GM) development, as shown by animal studies. However, associations among adverse parenting experiences during childhood and adolescence, HPA axis activity, and brain development, particularly hippocampal development, are insufficiently investigated in humans. In this voxel‐based structural magnetic resonance imaging study, using a cross‐sectional design, we examined the associations among the scores of parental bonding instrument (PBI; a self‐report scale to rate the attitudes of parents during the first 16 years), cortisol response determined by the dexamethasone/corticotropin‐releasing hormone test, and regional or total hippocampal GM volume in forty healthy young adults with the following features: aged between 18 and 35 years, no cortisol hypersecretion in response to the dexamethasone test, no history of traumatic events, or no past or current conditions of significant medical illness or neuropsychiatric disorders. As a result, parental overprotection scores significantly negatively correlated with cortisol response. Additionally, a significant positive association was found between cortisol response and total or regional hippocampal GM volume. No significant association was observed between PBI scores and total or regional hippocampal GM volume. In conclusion, statistical associations were found between parental overprotection during childhood and adolescence and adulthood HPA axis hypoactivity, and between HPA axis hypoactivity and hippocampal GM volume reduction in healthy young adults, but no significant relationship was observed between any PBI scores and adulthood hippocampal GM volume. Hum Brain Mapp 33:2211–2223, 2012. © 2011 Wiley Periodicals, Inc.
Diagnosis and treatment of minimal hepatic encephalopathy to prevent motor vehicle accidents: A cost-effectiveness analysis
Authors: Bajaj Jasmohan S. , Pinkerton Steven D. , Sanyal Arun J. , Heuman Douglas M.
Published: December 2011

Minimal hepatic encephalopathy (MHE) in cirrhosis is associated with impaired driving skills and increased risk of motor vehicle accidents (MVAs). Detection and treatment of MHE has the potential to reduce costs and morbidity associated with MVAs. We conducted a cost-effectiveness analysis to assess the benefits of different strategies of MHE diagnosis and treatment for reducing MVA-related societal costs. The analyses compared five MHE management strategies: (1) presumptive treatment of all cirrhosis patients; (2) diagnosis by neuropsychological exam (NPE) with treatment; (3) diagnosis by standard psychometric tests (SPTs) with treatment; (4) diagnosis by rapid screening using inhibitory control test (ICT) with treatment; and (5) no MHE diagnosis or treatment (status quo). Treatments considered were lactulose or rifaximin, which were assumed to reduce the MVA rate to the level of similarly aged noncirrhosis patients with benefit adjusted for treatment compliance. A Markov model followed a simulated cohort of 1,000 cirrhosis patients without overt hepatic encephalopathy (OHE), from entry into treatment, through MHE development, and later OHE, when they exited the modeled cohort. Follow-up was for 5 years and included biannual MHE testing. The societal cost of a single MVA was estimated at $42,100. All four strategies with lactulose were cost-saving compared with the status quo. Diagnosis with ICT and lactulose was the most cost-effective approach (cost/MVA prevented: $24,454 ICT; $25,470 SPT; $30,469 presumptive treatment and $33,742 NPE). Net program savings over 5 years ranged from $1.7 to 3.6 million depending on the strategy. Rifaximin therapy was not cost-saving at current prices but would become so at a monthly cost of <$353. Conclusion: Detection of MHE, especially using the ICT, and subsequent treatment with lactulose could substantially reduce societal costs by preventing MVAs. (Hepatology 2012)
Economic model of a birth cohort screening program for hepatitis C virus
Authors: McGarry Lisa J. , Pawar Vivek S. , Panchmatia Hemangi R. , Rubin Jaime L. , Davis Gary L. , Younossi Zobair M. , Capretta James C. , O'Grady Michael J. , Weinstein Milton C.
Published: December 2011

Recent research has identified high hepatitis C virus (HCV) prevalence among older U.S. residents who contracted HCV decades ago and may no longer be recognized as high risk. We assessed the cost-effectiveness of screening 100% of U.S. residents born 1946-1970 over 5 years (birth-cohort screening), compared with current risk-based screening, by projecting costs and outcomes of screening over the remaining lifetime of this birth cohort. A Markov model of the natural history of HCV was developed using data synthesized from surveillance data, published literature, expert opinion, and other secondary sources. We assumed eligible patients were treated with pegylated interferon plus ribavirin, with genotype 1 patients receiving a direct-acting antiviral in combination. The target population is U.S. residents born 1946-1970 with no previous HCV diagnosis. Among the estimated 102 million (1.6 million chronically HCV infected) eligible for screening, birth-cohort screening leads to 84,000 fewer cases of decompensated cirrhosis, 46,000 fewer cases of hepatocellular carcinoma, 10,000 fewer liver transplants, and 78,000 fewer HCV-related deaths. Birth-cohort screening leads to higher overall costs than risk-based screening ($80.4 billion versus $53.7 billion), but yields lower costs related to advanced liver disease ($31.2 billion versus $39.8 billion); birth-cohort screening produces an incremental cost-effectiveness ratio (ICER) of $37,700 per quality-adjusted life year gained versus risk-based screening. Sensitivity analyses showed that reducing the time horizon during which health and economic consequences are evaluated increases the ICER; similarly, decreasing the treatment rates and efficacy increases the ICER. Model results were relatively insensitive to other inputs.

Conclusion:

Birth-cohort screening for HCV is likely to provide important health benefits by reducing lifetime cases of advanced liver disease and HCV-related deaths and is cost-effective at conventional willingness-to-pay thresholds. (Hepatology 2012)
Comparative analysis of portal cell infiltrates in antimitochondrial autoantibody–positive versus antimitochondrial autoantibody–negative primary biliary cirrhosis
Authors: Jin Qinglong , Moritoki Yuki , Lleo Ana , Tsuneyama Koichi , Invernizzi Pietro , Moritoki Hitoshi , Kikuchi Kentaro , Lian Zhe-Xiong , Hirschfield Gideon M. , Ansari Aftab A. , Coppel Ross L. , Gershwin Eric M. , Niu Junqi
Published: December 2011

Substantial evidence supports dysregulated B-cell immune responses in patients with primary biliary cirrhosis (PBC), including the presence of serum antimitochondrial antibodies (AMAs). However, recent reports from murine models of PBC suggest that B cells may also provide regulatory function, and indeed the absence of B cells in such models leads to exacerbation of disease. The vast majority of patients with PBC have readily detectable AMAs, but a minority (<5%) are AMA negative (AMA−), even with recombinant diagnostic technology. This issue prompted us to examine the nature of B-cell infiltrates surrounding the portal areas in AMA-positive (AMA+) and AMA− patients, because they display indistinguishable clinical features. Of importance was the finding that the degree of bile duct damage around the portal areas was significantly milder in AMA+ PBC than those observed in AMA− PBC patients. The portal areas from AMA− patients had a significant increase of cluster of differentiation (CD)5+ cells infiltrating the ductal regions, and the levels of B-cell infiltrates were worse in the early phase of bile duct damage. The frequency of positive portal areas and the magnitude of CD5+ and CD20+ cellular infiltrates within areas of ductal invasion is associated with the first evidence of damage of biliary duct epithelia, but becomes reduced in the ductopenia stage, with the exception of CD5+ cells, which remain sustained and predominate over CD20+ cells.

Conclusion:

Our data suggest a putative role of B-cell autoimmunity in regulating the portal destruction characteristic of PBC. (Hepatology 2012)
Variants in ABCB1 , TGFB1 , and XRCC1 genes and susceptibility to viral hepatitis A infection in Mexican Americans
Authors: Zhang Lyna , Yesupriya Ajay , Hu Dale J. , Chang Man-huei , Dowling Nicole F. , Ned Renée M. , Udhayakumar Venkatachalam , Lou Lindegren Mary , Khudyakov Yury
Published: December 2011

Hepatitis A vaccination has dramatically reduced the incidence of hepatitis A virus (HAV) infection, but new infections continue to occur. To identify human genetic variants conferring a risk for HAV infection among the three major racial/ethnic populations in the United States, we assessed associations between 67 genetic variants (single nucleotide polymorphisms [SNPs]) among 31 candidate genes and serologic evidence of prior HAV infection using a population-based, cross-sectional study of 6,779 participants, including 2,619 non-Hispanic whites, 2,095 non-Hispanic blacks, and 2,065 Mexican Americans enrolled in phase 2 (1991–1994) of the Third National Health and Nutrition Examination Survey. Among the three racial/ethnic groups, the number (weighted frequency) of seropositivity for antibody to HAV was 958 (24.9%), 802 (39.2%), and 1540 (71.5%), respectively. No significant associations with any of the 67 SNPs were observed among non-Hispanic whites or non-Hispanic blacks. In contrast, among Mexican Americans, variants in two genes were found to be associated with an increased risk of HAV infection: TGFB1 rs1800469 (adjusted odds ratio [OR], 1.38; 95% confidence interval [CI], 1.14–1.68; P value adjusted for false discovery rate [FDR-P] = 0.017) and XRCC1 rs1799782 (OR, 1.57; 95% CI, 1.27–1.94; FDR-P = 0.0007). A decreased risk was found with ABCB1 rs1045642 (OR, 0.79; 95% CI, 0.71–0.89; FDR-P = 0.0007). Conclusion: Genetic variants in ABCB1, TGFB1, and XRCC1 appear to be associated with susceptibility to HAV infection among Mexican Americans. Replication studies involving larger population samples are warranted. (Hepatology 2012)
The cyclophilin inhibitor alisporivir prevents hepatitis C virus–mediated mitochondrial dysfunction
Authors: Quarato Giovanni , D'Aprile Annamaria , Gavillet Bruno , Vuagniaux Grégoire , Moradpour Darius , Capitanio Nazzareno , Piccoli Claudia
Published: December 2011

Alisporivir (Debio-025) is an analogue of cyclosporine A and represents the prototype of a new class of non-immunosuppressive cyclophilin inhibitors.

In vitro

and

in vivo

studies have shown that alisporivir inhibits hepatitis C virus (HCV) replication, and ongoing clinical trials are exploring its therapeutic potential in patients with chronic hepatitis C. Recent data suggest that the antiviral effect is mediated by inhibition of cyclophilin A, which is an essential host factor in the HCV life cycle. However, alisporivir also inhibits mitochondrial permeability transition by binding to cyclophilin D. Because HCV is known to affect mitochondrial function, we explored the effect of alisporivir on HCV protein-mediated mitochondrial dysfunction. Through the use of inducible cell lines, which allow to investigate the effects of HCV polyprotein expression independent from viral RNA replication and which recapitulate the major alterations of mitochondrial bioenergetics observed in infectious cell systems, we show that alisporivir prevents HCV protein-mediated decrease of cell respiration, collapse of mitochondrial membrane potential, overproduction of reactive oxygen species and mitochondrial calcium overload. Strikingly, some of the HCV-mediated mitochondrial dysfunctions could even be rescued by alisporivir.

Conclusion:

These observations provide new insights into the pathogenesis of HCV-related liver disease and reveal an additional mechanism of action of alisporivir that is likely beneficial in the treatment of chronic hepatitis C. (Hepatology 2012)