bluuebunny/crossref_metadata_2025 huggingface dataset:
[Zn(C3H3N2)(C3H2N2–N=N–C6H5)], a Mixed‐Linker ZIF Containing a Photo­switchable Phenylazo Group
Authors: Bernt Stephan , Feyand Mark , Modrow Antje , Wack Julia , Senker Jürgen , Stock Norbert
Published: October 2011

We report the synthesis and characterization of the new switchable Zn‐based zeolitic imidazolate framework (ZIF) [Zn(Im)(aIm)] (1). The high‐throughput investigation of the mixed linker system Zn2+/imidazole (HIm)/2‐phenylazoimidazole (HaIm)/DMF at 85 °C led to 1, which is isostructural to ZIF‐8 and crystallizes in a sodalite (SOD)‐type structure. The preparation was also studied with microwave‐assisted heating and ultrasound‐assisted synthesis. The crystal structure was determined from single‐crystal X‐ray diffraction data. Although Im– and aIm– ions are present in a 1:1 molar ratio, no ordering of the 2‐phenylazo group was observed. Incorporation of the Im– and aIm– linkers as an integral part of the framework structure was confirmed by elemental analysis, 13C and 15N MAS NMR, IR and Raman spectroscopy. In addition, the permanent porosity of 1 was demonstrated by N2 sorption experiments and a specific surface area of SBET = 580 m2 g–1 is observed. The photoswitching properties were investigated by UV/Vis spectroscopy as the cis and trans isomers exhibit different UV absorption spectra. Switching can be achieved by irradiation with UV light (λ = 355 nm), and back‐switching using visible light (λ = 525 nm). Although changes in the UV/Vis spectra are detected, the switching process is only partially reversible.
Effect of direct current dielectrophoresis on the trajectory of a non‐conducting colloidal sphere in a bent pore
Authors: House Dustin L. , Luo Haoxiang
Published: October 2011

Dielectrophoresis has shown a wide range of applications in microfluidic devices. Force approximations utilizing the point‐dipole method in dielectrophoresis have provided convenient predictions for particle motion by neglecting interactions between the particle and its surrounding electric and flow fields. The validity of this approach, however, is unclear when the particle size is comparable to the characteristic length of the channel and when the particle is in close proximity to the channel wall. To address this issue, we apply an accurate numerical approach based on the boundary‐element method (BEM) to solve the coupled electric field, flow, and particle motion. This method can handle much closer particle–wall distances than the other numerical approaches such as the finite‐element method. Using the BEM and integrating the Maxwell stress tensor, we simulate an electrokinetic, spherical particle moving within a bent cylindrical pore to investigate how the dielectrophoretic force affects the particle's trajectory. In the simulation, both the particle and the channel wall are non‐conducting, and the electric double layers adjacent to the solid surfaces are assumed to be thin with respect to the particle radius and particle–wall gap. The results show that as the particle comes close to the wall, its finite size has an increasingly important effect on its own transient motion and the point‐dipole approximation may lead to significant error.
Screening and characterization of microorganisms capable of converting iminodiacetonitrile to iminodiacetic acid
Authors: Zhang Jin‐Feng , Liu Zhi‐Qiang , Zheng Yu‐Guo , Shen Yin‐Chu
Published: October 2011

For screening and isolation of microorganisms harboring nitrile‐hydrolyzing enzymes that mediate the hydrolysis of iminodiacetonitrile (IDAN) to iminodiacetic acid (IDA), a sensitive and specific high‐throughput screening model was established. This model integrated a solid screen‐selective culture medium plate with bromcresol purple as the pH indicator coupled to Cu‐IDA complex spectrophotometry. Four strains were selected to perform the biotransformation to IDA, which were isolated and identified as Alcaligenes faecalis, Pseudomonas chlororaphis, Pseudomonas putida and Klebsiella pneumoniae, on the basis of 16S rDNA sequence analysis in combination with physiological and biochemical characterization. Moreover, the maximum specific enzyme activity was 73.4 U/g dry cell weight obtained by A. faecalis ZJUTBX11 after optimization of the medium conditions for enzyme production. The results show that the proposed model is a suitable method for screening microorganisms with nitrile‐hydrolyzing enzymes. We suggest the A. faecalis ZJUTBX11 strain to be used for large‐scale bioconversion of IDAN to IDA, because of its excellent performance in the production of IDA.
Addition of simvastatin to cold storage solution prevents endothelial dysfunction in explanted rat livers
Authors: Russo Lucia , Gracia-Sancho Jorge , García-Calderó Héctor , Marrone Giusi , García-Pagán Juan Carlos , García-Cardeña Guillermo , Bosch Jaime
Published: October 2011

Pathophysiological alterations in the endothelial phenotype result in endothelial dysfunction. Flow cessation, occurring during organ procurement for transplantation, triggers the endothelial dysfunction characteristic of ischemia/reperfusion injury, partly due to a reduction in the expression of the vasoprotective transcription factor Kruppel-like Factor 2 (KLF2). We aimed at (1) characterizing the effects of flow cessation and cold storage on hepatic endothelial phenotype, and (2) ascertaining if the consequences of cold stasis on the hepatic endothelium can be pharmacologically modulated, improving liver graft function. Expression of KLF2 and its vasoprotective programs was determined in (i) hepatic endothelial cells (HEC) incubated under cold storage conditions with or without the KLF2-inducer simvastatin, and (ii) rat livers not cold stored or preserved in cold University of Wisconsin solution (UWS) supplemented with simvastatin or its vehicle. In addition, upon warm reperfusion hepatic vascular resistance, endothelial function, nitric oxide vasodilator pathway, apoptosis, inflammation, and liver injury were evaluated in not cold stored livers or livers preserved in cold UWS supplemented with simvastatin or vehicle. Expression of KLF2 and its vasoprotective programs decrease in HEC incubated under cold storage conditions. Cold-stored rat livers exhibit a time-dependent decrease in KLF2 and its target genes, liver injury, increased hepatic vascular resistance, and endothelial dysfunction. The addition of simvastatin to the storage solution, maintained KLF2-dependent vasoprotective programs, prevented liver damage, inflammation, and oxidative stress and improved endothelial dysfunction.

Conclusion :

Our results provide a rationale to evaluate the beneficial effects of a vasoprotective preservation solution on human liver procurement for transplantation.
Plasma cells and the chronic nonsuppurative destructive cholangitis of primary biliary cirrhosis
Authors: Takahashi Toru , Miura Tomofumi , Nakamura Junichiro , Yamada Satoshi , Miura Tsutomu , Yanagi Masahiko , Matsuda Yasunobu , Usuda Hiroyuki , Emura Iwao , Tsuneyama Koichi , He Xiao-Song , Gershwin Eric M.
Published: October 2011

There has been increased interest in the role of B cells in the pathogenesis of primary biliary cirrhosis (PBC). Although the vast majority of patients with this disease have anti-mitochondrial antibodies, there is no correlation of anti-mitochondrial antibody titer and/or presence with disease severity. Furthermore, in murine models of PBC, it has been suggested that depletion of B cells may exacerbate biliary pathology. To address this issue, we focused on a detailed phenotypic characterization of mononuclear cell infiltrates surrounding the intrahepatic bile ducts of patients with PBC, primary sclerosing cholangitis, autoimmune hepatitis, chronic hepatitis C, and graft-versus-host disease, including CD3, CD4, CD8, CD20, CD38, and immunoglobulin classes, as well as double immunohistochemical staining for CD38 and IgM. Interestingly, CD20 B lymphocytes, which are a precursor of plasma cells, were found in scattered locations or occasionally forming follicle-like aggregations but were not noted at the proximal location of chronic nonsuppurative destructive cholangitis. In contrast, there was a unique and distinct coronal arrangement of CD38 cells around the intrahepatic ducts in PBC but not controls; the majority of such cells were considered plasma cells based on their expression of intracellular immunoglobulins, including IgM and IgG, but not IgA. Patients with PBC who manifest this unique coronal arrangement were those with significantly higher titers of anti-mitochondrial antibodies.

Conclusion :

These data collectively suggest a role for plasma cells in the specific destruction of intrahepatic bile ducts in PBC and confirm the increasing interest in plasma cells and autoimmunity.
Humanized chimeric uPA mouse model for the study of hepatitis B and D virus interactions and preclinical drug evaluation
Authors: Lütgehetmann Marc , Mancke Lida V. , Volz Tassilo , Helbig Martina , Allweiss Lena , Bornscheuer Till , Pollok Joerg M. , Lohse Ansgar W. , Petersen J. , Urban Stephan , Dandri Maura
Published: October 2011

No specific drugs are currently available against hepatitis delta virus (HDV), a defective virus leading to the most severe form of chronic viral hepatitis in man. The lack of convenient HDV infection models has hampered the development of effective therapeutics. In this study, naïve and hepatitis B virus (HBV) chronically infected humanized uPA/SCID mice were employed to establish a small animal model of HBV/HDV coinfection and superinfection. For preclinical antiviral drug evaluation, the GMP version of the myristoylated preS-peptide (Myrcludex-B), a lipopeptide derived from the pre-S1 domain of the HBV envelope, was applied to prevent

de novo

HBV/HDV coinfection

in vivo

. Virological parameters were determined at serological and intrahepatic level both by real-time polymerase chain reaction (PCR) and by immunohistochemistry. Establishment of HDV infection was highly efficient in both HBV-infected and naïve chimeric mice with HDV titers rising up to 1 × 10E9 copies/mL. Notably, HDV superinfection led to a median 0.6log reduction of HBV viremia, which although not statistically significant suggests that HDV may hinder HBV replication. In the setting of HBV/HDV simultaneous infection, a majority of human hepatocytes stained HDAg-positive long before HBV spreading was completed, confirming that HDV can replicate intrahepatically also in the absence of HBV infection. Furthermore, the increase of HBV viremia and intrahepatic cccDNA loads was significantly slower than in HBV mono-infected mice. Treatment with the HBV entry inhibitor Myrcludex-B, efficiently hindered the establishment of HDV infection

in vivo

.

Conclusion :

We established an efficient model of HBV/HDV infection to exploit mechanisms of viral interference in human hepatocytes and to test the efficacy of an HDV-entry inhibitor

in vivo

.
Activation of chemokine and inflammatory cytokine response in hepatitis C virus–infected hepatocytes depends on toll-like receptor 3 sensing of hepatitis C virus double-stranded RNA intermediates
Authors: Li Kui , Li Nan L. , Wei Dahai , Pfeffer Susan R. , Fan Meiyun , Pfeffer Lawrence M.
Published: October 2011

Chemokines and inflammatory cytokines are key regulators of immunity and inflammation during viral infections. Hepatitis C virus (HCV) is a hepatotropic RNA virus frequently associated with chronic liver inflammation and hepatocellular carcinoma. Intrahepatic levels of chemokines and cytokines are elevated in chronic HCV infections, but the underlying mechanisms remain unclear. We found that Toll-like receptor-3 (TLR3) senses HCV infection in cultured hepatoma cells, leading to nuclear factor kappa B (NF-κB) activation and the production of numerous chemokines and inflammatory cytokines, such as regulated on activation normal T cell expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1α, MIP-1β, IP-10, and interleukin-6. The chemokine/cytokine induction occurred late in HCV infection and was abrogated when HCV was ultraviolet-inactivated before infection, indicating a dependence on the cellular recognition of HCV replication products. Gel-shift and chromatin immunoprecipitation assays revealed that NF-κB plays a pivotal role in HCV-induced chemokine/cytokine transcription. Mutations specifically disrupting the double-stranded RNA (dsRNA)-binding activity of TLR3 ablated the chemokine/cytokine response to HCV infection, indicating that HCV dsRNA was the pathogen-associated molecular pattern triggering TLR3 signaling.

In vitro

synthesized HCV dsRNAs, with a minimal length of ˜80-100 base pairs, activated TLR3-dependent chemokine expression, regardless of the genome position from which they derived. In contrast, HCV single-stranded RNAs, including those derived from the structured 3'nontranslated region highly potent for RIG-I activation, failed to do so. Moreover, robust production of chemokines and inflammatory cytokines was also observed in primary human hepatocytes after stimulation with extracellular poly-I:C, a TLR3 ligand.

Conclusion :

Our data suggest that TLR3-mediated chemokine and inflammatory cytokine responses may play an important role in host immune responses to HCV and the pathogenesis of HCV-associated liver diseases.
Growth-hormone–induced signal transducer and activator of transcription 5 signaling causes gigantism, inflammation, and premature death but protects mice from aggressive liver cancer
Authors: Friedbichler Katrin , Themanns Madeleine , Mueller Kristina M. , Schlederer Michaela , Kornfeld Jan-Wilhelm , Terracciano Luigi M. , Kozlov Andrey V. , Haindl Susanne , Kenner Lukas , Kolbe Thomas , Mueller Mathias , Snibson Kenneth J. , Heim Markus H. , Moriggl Richard
Published: October 2011

Persistently high levels of growth hormone (GH) can cause liver cancer. GH activates multiple signal-transduction pathways, among them janus kinase (JAK) 2-signal transducer and activator of transcription (STAT) 5 (signal transducer and activator of transcription 5). Both hyperactivation and deletion of STAT5 in hepatocytes have been implicated in the development of hepatocellular carcinoma (HCC); nevertheless, the role of STAT5 in the development of HCC as a result of high GH levels remains enigmatic. Thus, we crossed a mouse model of gigantism and inflammatory liver cancer caused by hyperactivated GH signaling (GHtg) to mice with hepatic deletion of STAT5 (STAT5Δhep). Unlike GHtg mice, GHtgSTAT5Δhep animals did not display gigantism. Moreover, the premature mortality, which was associated with chronic inflammation, as well as the pathologic alterations of hepatocytes observed in GHtg mice, were not observed in GHtg animals lacking STAT5. Strikingly, loss of hepatic STAT5 proteins led to enhanced HCC development in GHtg mice. Despite reduced chronic inflammation, GHtgSTAT5Δhep mice displayed earlier and more advanced HCC than GHtg animals. This may be attributed to the combination of increased peripheral lipolysis, hepatic lipid synthesis, loss of hepatoprotective mediators accompanied by aberrant activation of tumor-promoting c-JUN and STAT3 signaling cascades, and accumulation of DNA damage secondary to loss of cell-cycle control. Thus, HCC was never observed in STAT5Δhep mice.

Conclusion :

As a result of their hepatoprotective functions, STAT5 proteins prevent progressive fatty liver disease and the formation of aggressive HCC in the setting of hyperactivated GH signaling. At the same time, they play a key role in controlling systemic inflammation and regulating organ and body size.
Serum free light chains in myeloma patients with an intact M protein by immunofixation: potential roles for response assessment and prognosis during induction therapy with novel agents
Authors: Mori Sherry , Crawford Brooke S , Roddy Julianna VF , Phillips Gary , Elder Pat , Hofmeister Craig C , Efebera Yvonne , Benson Don M
Published: October 2011

The ascertainment of serum free light chain (sFLC) levels has been shown to be valuable in screening for the presence of plasma cell dyscrasia as well as for baseline prognosis in newly diagnosed patients. For patients with amyloidosis and those with oligo‐secretory or non‐secretory multiple myeloma (MM), serial measurement of sFLC has also been shown to be valuable in monitoring disease status. However, in patients with a measureable, intact monoclonal protein by immunofixation (M protein), the serial measurement of sFLC remains undefined and is currently not recommended in professional guidelines. Herein, we provide data comparing sFLC with M protein as biomarkers of response in newly diagnosed patients with MM undergoing induction therapy with the novel agents thalidomide, lenalidomide and/or bortezomib. We show that although M protein appears to outperform sFLC comparatively over the course of induction therapy, the addition of FLC to M protein further informs the characterization of residual disease status post‐induction. Moreover, sFLC at the time of stem cell mobilization appears to hold prognostic power for survival endpoints following high‐dose chemotherapy/autologous stem cell transplant (HDC/SCT). These findings suggest potentially novel roles for sFLC in patients with MM with an intact M protein receiving novel agent‐based induction strategies followed by HDC/SCT. Copyright © 2011 John Wiley & Sons, Ltd.
Selenoglutathione‐Mediated Rescue of Kinetically Trapped Intermediates in Oxidative Protein Folding
Authors: Metanis Norman , Foletti Carlotta , Beld Joris , Hilvert Donald
Published: October 2011

Selenoglutathione has been shown to have considerable potential as a catalyst of oxidative protein folding. Here we examine how this reagent modulates the folding pathway of bovine pancreatic trypsin inhibitor (BPTI) and show that the diselenide increases the efficiency of this process primarily by accelerating the conversion of a kinetically trapped folding intermediate.
Many routes to a micro RNA
Authors: Yeo Janet H. C. , Chong Mark M. W.
Published: October 2011

Micro RNAs (miRNAs) are ∼22 nt small RNAs that function as posttranscriptional negative regulators of gene expression. Thousands of these molecules have so far been identified across the metazoan and plant kingdoms. Although most miRNAs share the same biogenesis pathway, numerous noncanonical miRNAs and other small RNAs have also been identified. In this review, we will discuss these alternate small RNA biogenesis pathways as well as recent discoveries of non‐miRNA functions of the miRNA biogenesis machinery. This review will focus only on metazoan pathways. © 2011 IUBMB IUBMB Life, 63(11): 972–978, 2011
Insight into the role of a unique SSEHA motif in the activity and stability of Helicobacter pylori arginase
Authors: Srivastava Abhishek , Dwivedi Nidhi , Samanta Uttamkumar , Sau Apurba Kumar
Published: October 2011

Arginase is a binuclear Mn2+‐metalloenzyme of urea cycle that hydrolyzes arginine to ornithine and urea. Unlike other arginases, the Helicobacter pylori enzyme is selective for Co2+ and has all conserved motifs except 88SSEHA92 (instead of GGDHS). To examine the role of this motif in the activity and stability, steady‐state kinetics, mutational analysis, thermal denaturation, and homology modeling were carried out. With a series of single and double mutants, we show that mutations of Ser88 and Ala92 to its analogous residues in other arginases individually enhance the catalytic activity. This is supported by the modeling studies, where the motif plays a role in alteration at the active site structure compared to other arginases. Mutational analysis further shows that both Glu90 and His91 are important for the activity, as their mutations lead to significant decrease in the catalytic efficiency but they appear to act in two different ways; Glu90 has a more catalytic role as its mutant displays binding of the two metal ions per monomer of the protein, but His91 plays a critical role in retaining the metal ion at the active site as its mutation exhibits a loss of one metal ion. Thermal denaturation studies demonstrated that Ser88 and His91 both play crucial roles in the stability of the protein as their mutants showed a decrease in the Tm by ∼10–11°. Unlike wild type, the metal ions have larger role in providing the stability to the mutant proteins. Thus, our data demonstrate that the motif not only plays an important role in the activity but also critical in the stability of the protein. © 2011 IUBMB IUBMB Life, 63(11): 1027–1036, 2011
A new function for the calcineurin b subunit: Antiplatelet aggregation and anticoagulation
Authors: Su Zhenyi , Xin Shuai , Li Jing , Guo Junxia , Long Xianlian , Cheng Jinbo , Wei Qun
Published: October 2011

Calcineurin is the only Ca2+/calmodulin‐dependent serine/threonine protein phosphatase. The roles of the cytosolic calcineurin have been well researched; however, the roles of the serum calcineurin remain unknown. Here, we report that the recombinant human calcineurin B subunit (CnB) can bind to rabbit platelets and show an antiplatelet aggregation activity. Furthermore, CnB exerts an anticoagulant effect by prolonging the activated partial thromboplastin time and thrombin time and reducing the plasma fibrinogen concentration in a dose‐dependent manner. We further reveal that the functional domain associated with the anticoagulant activity of CnB is located in the C‐terminus. Hemolysis test and intravenous stimulation study show that the recombinant CnB does not cause obvious hemolysis and is safe for intravenous injection. These results reveal a new function of calcineurin B subunit. They also give an explanation for the roles of calcineurin B subunit in serum and point to a possible implication in antithrombotic therapy. © 2011 IUBMB IUBMB Life, 63(11): 1037–1044, 2011
New insights into therapeutic options for Pompe disease
Authors: Richard Emmanuel , Douillard‐Guilloux Gaëlle , Caillaud Catherine
Published: October 2011

Different cellular steps of acid maltase synthesis and subsequent glycogen degradation, by Emmanuel Richard, Gaëlle Douillard–Guilloux, and Catherine Caillaud, pp. 979–986.
EUCLIDEAN REVEALED PREFERENCES: TESTING THE SPATIAL VOTING MODEL
Authors: Henry Marc , Mourifié Ismael
Published: October 2011

In the spatial model of voting, voters choose the candidate closest to them in the ideological space. Recent work by Degan and Merlo in 2009 shows that it is falsifiable on the basis of individual voting data in multiple elections. We show how to tackle the fact that the model only partially identifies the distribution of voting profiles and we give a formal revealed preference test of the spatial voting model in three national elections in the USA, and strongly reject the spatial model in all cases. We also construct confidence regions for partially identified voter characteristics in an augmented model with unobserved valence dimension, and identify the amount of voter heterogeneity necessary to reconcile the data with spatial preferences. Copyright © 2011 John Wiley & Sons, Ltd.
Differential biodistribution of oncolytic poxvirus administered systemically in an autochthonous model of hepatocellular carcinoma
Authors: Baril Patrick , Touchefeu Yann , Cany Jeannette , Cherel Yan , Thorne Steve H. , Tran Lucile , Conchon Sophie , Vassaux Georges
Published: October 2011

Background

Preclinical studies have demonstrated that, unlike oncolytic adenoviruses, oncolytic vaccinia viruses can reach implanted tumors upon systemic injection. However, the biodistribution of this oncolytic agent in in situ autochthonous tumor models remains poorly characterized. In the present study, we assessed this biodistribution in a model of mouse hepatocellular carcinoma (HCC) obtained after injection of the carcinogen diethylnitrosamine (DEN).

Methods

Twelve months after DEN administration, histology, quantitative reverse transcription‐polymerase chain reaction, in situ hybridization and viral titration were used to characterize tumors, as well as to assess the viral load of the livers upon either intravenous or intraperitoineal injection.

Results

The results obtained showed that the architecture of the liver was lost, with a noticeable absence of sinusoids, as well as the presence of steatosis and α‐fetoprotein‐positive HCC tumor nodules. Bioluminescence imaging and measures of the infective virus load demonstrated that intravenous injection of 108 plaque‐forming units of the recombinant vaccinia virus led to a predominant transduction of the liver, whereas intraperitoneal injection resulted in a lower level of liver transduction accompanied by an increased infection of the lungs, spleen, kidneys and bowels. Immunohistochemical analysis of liver sections of animals injected intravenously with the virus revealed a preferential localization of vaccinia‐specific immunoreactivity in the tumors.

Conclusions

The findings of the present study emphasize the importance of the route of administration of the vector and highlight the relevance of systemic injection of oncolytic vaccinia virus in the context of hepatocellular carcinoma. Copyright © 2011 John Wiley & Sons, Ltd.
Differences in designations of observation care in US freestanding children's hospitals: Are they virtual or real?
Authors: Macy Michelle L. , Hall Matthew , Shah Samir S. , Hronek Carla , Del Beccaro Mark A. , Hain Paul D. , Alpern Elizabeth R.
Published: October 2011

OBJECTIVE:

To characterize practices related to observation care and to examine the current models of pediatric observation medicine in US children's hospitals.

DESIGN:

We utilized 2 web‐based surveys to examine observation care in the 42 hospitals participating in the Pediatric Health Information System database. We obtained information regarding the designation of observation status, including the criteria used to admit patients into observation. From hospitals reporting the use of observation status, we requested specific details relating to the structures of observation care and the processes of care for observation patients following emergency department treatment.

RESULTS:

A total of 37 hospitals responded to Survey 1, and 20 hospitals responded to Survey 2. Designated observation units were present in only 12 of 31 (39%) hospitals that report observation patient data to the Pediatric Health Information System. Observation status was variably defined in terms of duration of treatment and prespecified criteria. Observation periods were limited to <48 hours in 24 of 31 (77%) hospitals. Hospitals reported that various standards were used by different payers to determine observation status reimbursement. Observation care was delivered in a variety of settings. Most hospitals indicated that there were no differences in the clinical care delivered to virtual observation status patients when compared with other inpatients.

CONCLUSIONS:

Observation is a variably applied patient status, defined differently by individual hospitals. Consistency in the designation of patients under observation status among hospitals and payers may be necessary to compare quality outcomes and costs, as well as optimize models of pediatric observation care.Journal of Hospital Medicine 2012;. © 2011 Society of Hospital Medicine.
Preparation of technetium‐99m bifunctional chelate complexes using a microfluidic reactor: a comparative study with conventional and microwave labeling methods
Authors: Simms Ryan W. , Causey Patrick W. , Weaver Darren M. , Sundararajan Chitra , Stephenson Karin A. , Valliant John F.
Published: October 2011

A series of reactions between the technetium tricarbonyl core, [99mTc(CO)3(OH2)3]+ and both the bifunctional chelate dithiazole valeric acid (DTV) and insulin derivatized with DTV were performed using microfluidic, microwave, and conventional labeling methods. At low concentrations of ligand, the microfluidic reactor resulted in higher yields than both the microwave and conventional reactions. The labeling of DTV at a concentration of 0.01 mg/ml (32.2 µm) and 100 °C did not occur using conventional techniques, whereas the yield after 7.85 min was 61% in the microfluidic reactor and 18% in the microwave reactor. The labeling of a DTV–insulin conjugate (2.1 mg/ml, 330 µm) at 37 °C was conducted using conventional methods producing the desired product in 21% yield in 15.7 min compared with 40% of the desired product in the identically formulated microfluidic reactor. In addition to the higher radiochemical yield, the radiochemical purity was significantly improved in the microfluidic reactor. The microfluidic reactor offers a number of advantages over conventional and microwave methods and is worthy of further exploration as a method to prepare molecular imaging probes derived from Tc‐99m. Copyright © 2011 John Wiley & Sons, Ltd.
Automatic lumen and outer wall segmentation of the carotid artery using deformable three‐dimensional models in MR angiography and vessel wall images
Authors: van 't Klooster Ronald , de Koning Patrick J.H. , Dehnavi Reza Alizadeh , Tamsma Jouke T. , de Roos Albert , Reiber Johan H.C. , van der Geest Rob J.
Published: October 2011

Purpose:

To develop and validate an automated segmentation technique for the detection of the lumen and outer wall boundaries in MR vessel wall studies of the common carotid artery.

Materials and Methods:

A new segmentation method was developed using a three‐dimensional (3D) deformable vessel model requiring only one single user interaction by combining 3D MR angiography (MRA) and 2D vessel wall images. This vessel model is a 3D cylindrical Non‐Uniform Rational B‐Spline (NURBS) surface which can be deformed to fit the underlying image data. Image data of 45 subjects was used to validate the method by comparing manual and automatic segmentations. Vessel wall thickness and volume measurements obtained by both methods were compared.

Results:

Substantial agreement was observed between manual and automatic segmentation; over 85% of the vessel wall contours were segmented successfully. The interclass correlation was 0.690 for the vessel wall thickness and 0.793 for the vessel wall volume. Compared with manual image analysis, the automated method demonstrated improved interobserver agreement and inter‐scan reproducibility. Additionally, the proposed automated image analysis approach was substantially faster.

Conclusion:

This new automated method can reduce analysis time and enhance reproducibility of the quantification of vessel wall dimensions in clinical studies. J. Magn. Reson. Imaging 2012;35:156‐165. © 2011 Wiley Periodicals, Inc.
Ultrahigh‐field DCE‐MRI of angiogenesis in a novel angiogenesis mouse model
Authors: Wittenborn Thomas , Nielsen Thomas , Nygaard Jens V. , Larsen Esben K.U. , Thim Troels , Rydtoft Louise M. , Vorup‐Jensen Thomas , Kjems Jørgen , Nielsen Niels Chr. , Horsman Michael R. , Falk Erling
Published: October 2011

Purpose:

To be able to screen and identify potential candidate agents for noninvasive imaging of diseases involving angiogenesis, a standardized in vivo angiogenesis model is needed. Angiogenesis is a common feature of many pathological conditions and has become an important target for diagnosis and treatment, with many noninvasive imaging agents emerging.

Materials and Methods:

Uniform scaffolds consisting of porous and flexible polycaprolactone were implanted subcutaneously in mice and studied after 1 to 6 weeks to describe the time course of angiogenesis. The model was characterized by histology and dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI).

Results:

Microscopic examination revealed progressive ingrowth of new vessels from the periphery, leading to a fully vascularized scaffold within 6 weeks. Blood flow through the new vessels, assessed by DCE‐MRI, revealed peripheral vascularization corresponding to 12.3% (SD 6.1%) of scaffold area at week 1 and a more uniform and complete distribution of vessels corresponding to 84.1% (SD 16.2%) of scaffold area at week 4.

Conclusion:

In agreement with microscopic examination, noninvasive DCE‐MRI visualized progressive development of new vessels in a novel and standardized murine angiogenesis model, making this model suitable for screening angiogenesis‐related drugs and contrast agents. J. Magn. Reson. Imaging 2012;35:703‐710. © 2011 Wiley Periodicals, Inc.
Novel unbreakable solid‐phase microextraction fiber by electrodeposition of silica sol–gel on gold
Authors: Bagheri Habib , Sistani Habiballah , Ayazi Zahra
Published: October 2011

A new technique for preparation of an unbreakable solid‐phase microextraction (SPME) fiber, using sol–gel technology is developed. Primarily, an ultrathin two‐dimensional intermediate film was prepared by hydrolysis of 3‐(trimethoxysilyl)‐1‐propanthiol self‐assembled monolayer grafted onto gold, then a stationary phase by electrodeposition of 3‐(trimethoxysilyl)propylmethacrylate as a precursor, tetramethyl orthosilicate and polyethylene glycol as a coating polymer was produced. The scanning electron microscopy images revealed that the new fiber exhibits a rather porous and homogenous surface. The thermal stability of the fabricated fiber was investigated by thermogravimetric analysis. The applicability of the prepared fiber coating in conjunction with gas chromatography‐mass spectrometry was examined by SPME of polycyclic aromatic hydrocarbons, as model analytes, from aquatic media. An extraction time of 20 min at 50°C gave maximum peak areas when NaCl, 15% was added to the aqueous samples. Limits of detection were in the range of 0.01–0.02 ng/mL and relative standard deviation values were in the range of 4–16% at 1 ng/mL. The developed method was successfully applied for the analysis of real water samples while the relative recovery percentage was in the range of 102–118%.
Method development for fingerprinting of biodiesel blends by solid‐phase extraction and gas chromatography–mass spectrometry
Authors: Yang Zeyu , Hollebone Bruce P. , Wang Zhendi , Yang Chun , Landriault Mike
Published: October 2011

A method based on the combination of solid‐phase extraction (SPE) with gas chromatography–mass spectrometry (GC/MS) for detailed chemical fingerprinting of biodiesel/petrodiesel blends was developed in the present study. Forensic identification, commonly referred to as chemical fingerprinting, is based on the relative distributions of individual aliphatic hydrocarbons, aromatic hydrocarbons, fatty acid alkyl esters, and free sterols. Fractionation of fuel samples is optimized for the separation of fatty acid esters and free sterols from petroleum hydrocarbons into four fractions: aliphatic, aromatic, fatty acid ester, and polar components. The final recoveries of aliphatic and aromatic hydrocarbons were determined to be in the range of 65–103%, 73–105% for FAMEs, and 78–103% for free sterols in the polar fraction. Excellent separation with negligible crossover of components with different polarities between fractions was observed. Quantitative analysis of blend levels and individual chemical distribution were achieved. The method has great potential for the identification of biodiesel in diesel fuel blends and could form the basis of a method for characterization of biodiesel‐contaminated environmental samples.
Fast dynamic contrast‐enhanced lung MR imaging using k–t BLAST: A spatiotemporal perspective
Authors: Hsu Jia‐Shuo , Tsai Shang‐Yuei , Wu Ming‐Ting , Chung Hsiao‐Wen , Lin Yi‐Ru
Published: October 2011

Dynamic contrast‐enhanced MR imaging has long been an attractive alternative to measure pulmonary perfusion as it offers simultaneous acquisition of high‐resolution anatomical images and various functional information without exposing to ionizing radiation. As higher temporal resolution in addition to simultaneous acquisition of more slices from different positions favors more precise diagnosis, rapid acquisition of multiple images during bolus contrast administration remains essential to pulmonary perfusion imaging. Nevertheless, the branching morphology together with asynchronization of contrast‐enhanced pulmonary perfusion scattered among distinct blood vessels imposes difficulties to faster imaging. This work demonstrates that k–t broad‐use linear acquisition speed‐up technique (k–t BLAST), having substantial performance on accelerating cardiac cine imaging, can be applied to accelerate dynamic contrast‐enhanced lung imaging up to a factor of 5 with errors less than 6% on five healthy subjects and less than 10% on 13 patients, respectively, in the overall signal intensity. Perfusion parameter estimates show somewhat less errors than those in overall signal intensity. Results from healthy subjects and two groups of patients with various diseases show high consistency between fully sampled datasets and their accelerated counterparts. These suggest feasibility of accelerated contrast‐enhanced lung images in clinical examinations and potential of extending k–t BLAST into related applications. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.
Numerical integration of a pressure‐dependent, non‐linear kinematic hardening constitutive model for large strain cyclic plasticity of metals
Authors: Panteghini Andrea , Genna Francesco
Published: October 2011

A Gurson‐based constitutive model is presented, which includes non‐linear mixed isotropic–kinematic hardening and creep, and allows the analysis of problems involving arbitrarily large plastic strains. This model was developed with the main objective of allowing, on the basis of a single set of material parameters, the numerical simulation of all the main features of cold metal forming processes, which usually imply severe loading–unloading cycles with very large plastic strains, difficult to be correctly reproduced numerically. A suitable integration scheme of the rate equations is described and implemented into a finite element code. The results obtained are compared with some reference experimental ones; an application of the model for the simulation of wire drawing processes is also presented. Copyright © 2011 John Wiley & Sons, Ltd.
Toward a multifrequency quasi‐static Ritz vector method for frequency‐dependent acoustic system application
Authors: Yoon Gil Ho
Published: October 2011

Computational issues concerning the calculation of acoustic responses of a complex finite element (FE) model for various noise and vibration inputs have become prevalent. Such a model requires a significant amount of computation time because of repeated inversions of dynamic stiffness matrices. Thus, even state‐of‐the‐art computer hardware and software often face limitations where a model order reduction (MOR) scheme can help. The established MOR schemes such as Ritz vector or quasi‐static Ritz vector methods are efficient for general engineering systems, but these MOR methods become inaccurate for frequency response analyses in some acoustic systems with frequency‐dependent mass and stiffness matrices and force vectors (hereinafter frequency‐dependent acoustic systems). To cope with the inaccurate prediction by these methods for frequency‐dependent acoustic systems, this research presents and applies the multifrequency quasi‐static Ritz vector method. Unlike the Ritz vector or quasi‐static Ritz vector methods, the present multifrequency quasi‐static Ritz vector method employs direct Krylov subspace bases without an orthonormal procedure at multiple center frequencies. In comparison with the existing MOR scheme, a significant gain in computational efficiency is achieved, as well as enhanced accuracy. A comparison of these methods based on criteria such as efficiency, accuracy, and reliability was also conducted. Copyright © 2011 John Wiley & Sons, Ltd.
Hemocompatible polyurethane surfaces
Authors: Wu Zhaoqiang , Chen Hong , Liu Xiaoli , Brash John L.
Published: October 2011

With the aim of improving the hemocompatibility of blood‐contacting devices, antithrombotic or fibrinolytic biological molecules‐containing polyurethane (PU) materials have been developed. Cationic PU surfaces were prepared by grafting poly(dimethylaminoethyl methacrylate) and quaternizing the tertiary amino groups with iodomethane. The surfaces were characterized by water contact angles and X‐ray photoelectron spectroscopy. The materials (PU‐CH3I) were treated with antithrombotic or fibrinolytic drugs, such as hirudin or tissue plasminogen activator (tPA) in Tris‐buffered saline (pH 9.0) to yield hirudin‐loaded or tPA‐loaded PU surfaces. The hirudin and tPA quantity of the surfaces was observed using a radiolabeling method. The quantities of hirudin and tPA taken up by the cationic surfaces were significantly greater than those on the unmodified PU: approximately 200‐fold greater for hirudin and 10‐fold for tPA. The release of the bound hirudin and tPA from the materials in contact with plasma was slow, and at 48 h, ~78% of the initial hirudin and ~26% of the initial tPA remained bound. The activity of the bound hirudin and tPA, as measured by a plasma recalcification assay, was largely preserved. This approach may have potential for the development of surfaces having antithrombotic or fibrinolytic properties. Copyright © 2011 John Wiley & Sons, Ltd.
Attitudes toward prenatal testing and pregnancy termination among a diverse population of parents of children with intellectual disabilities
Authors: Kuppermann Miriam , Nakagawa Sanae , Cohen Shana Raquel , Dominguez‐Pareto Irenka , Shaffer Brian L. , Holloway Susan D.
Published: October 2011

Objective

To determine how parents of children with intellectual disabilities view prenatal testing and pregnancy termination for their child's condition.

Method

We interviewed 201 English‐speaking or Spanish‐speaking caregivers of children aged 2 to 10 years. Primary outcomes were being disinclined to undergo prenatal testing or pregnancy termination for the child's condition in a future pregnancy.

Results

While only 33% of the sample indicated they would not have prenatal testing, 75% were disinclined to terminate their pregnancy if their fetus was affected. In multivariable logistic regression analysis, Asians were significantly less likely than White participants to say they would forego prenatal testing (adjusted odds ratio (aOR) = 0.08, 95% confidence interval (CI) = 0.01–0.86, p = 0.037), while Latinos had lower odds of being disinclined to terminate (aOR = 0.27, 95% CI = 0.07–0.99, p = 0.048). Participants who felt that abortion for their child's condition should not be available were more likely to say they would forego prenatal testing (aOR = 5.10, 95% CI = 2.09–12.43, p < 0.001) and, not surprisingly, they were also at higher odds of being disinclined to terminate pregnancy for this condition (aOR = 13.63, 95% = CI 4.19–44.34, p < 0.001). Greater life satisfaction also was associated with being disinclined to terminate pregnancy (aOR = 3.40, 95% CI = 1.34–8.61, p = 0.010).

Conclusion

Although many parents of children with intellectual disabilities believe they would desire information regarding their fetus in a future pregnancy, most feel they would not opt to terminate their pregnancy. As new tests for intellectual disabilities become available, determining what would be most useful to prospective parents should become a high priority. Copyright © 2011 John Wiley & Sons, Ltd.
Measurement of nuchal translucency for prenatal screening of congenital heart defects: a population‐based evaluation
Authors: Jouannic Jean‐Marie , Thieulin Anne‐Claire , Bonnet Damien , Houyel Lucile , Lelong Nathalie , Goffinet François , Khoshnood Babak
Published: October 2011

Objectives

(1) Assess sensitivity of the measurement of nuchal translucency (NT), for the prenatal screening of congenital heart defect (CHD) on population‐based data; (2) examine whether the sensitivity of NT varies for specific types of cardiac defects.

Methods

Using population‐based data of the Paris Registry of Congenital Malformation for 935 fetuses with CHD and without chromosomal anomalies for the period 2001 to 2007, we calculated sensitivity of NT, its positive predictive value and likelihood ratio, for all CHD and for six types of CHD.

Results

Sensitivity of NT was 7.1 and 4.2% for the 2.5 and 3.5 mm cut‐off values, respectively; when isolated ventricular septal defects were excluded, sensitivity increased to 9.9 and 6.3%. Positive predictive values were 1.1 and 3.2% for 2.5 and 3.5 mm cut‐offs, respectively. Of the six defects examined, sensitivity of NT was highest for heterotaxy followed by hypoplastic left heart syndrome and coarctation of aorta.

Conclusion

Prevalence of CHD was about fourfold higher for fetuses with NT ≥ 3.5 mm (3.2%) than in the general population. This higher risk is comparable to that of other risk factors commonly used for early referral to specialized echocardiography. Nevertheless, our results, suggest that NT is not a very effective or efficient tool for the prenatal screening of CHD. Copyright © 2011 John Wiley & Sons, Ltd.
Late termination of pregnancy for fetal abnormalities: The perspective of Indian lay persons and medical practitioners
Authors: Phadke Shubha R. , Agarwal Meenal , Aggarwal Shagun
Published: October 2011

Objective

The objective of this article was to ascertain the opinion of lay persons and medical practitioners in India regarding late termination of pregnancies (LTOP) for fetal abnormalities.

Methods

One hundred and fifty lay persons and 120 medical practitioners were given separate questionnaires and asked their opinions regarding LTOP for prenatally detected fetal abnormalities of varying severity. The views regarding legalisation of LTOP and the acceptability of feticide by the lay persons were also ascertained.

Results

More than two‐thirds of the lay persons and majority (85.8%) of clinicians felt that LTOP should be allowed for fetal conditions with poor prognosis. At least 70% of lay persons felt that LTOP should be legalised for severe fetal abnormalities. For potentially treatable conditions, continuation of pregnancy in late gestation was the preferred option. For lethal malformations like anencephaly and disorders requiring lifelong treatment like meningomylocele and thalassemia major, majority of clinicians (86.7%, 69.2% and 55.8%, respectively) and lay persons (65%, 51% and 25%, respectively) had the opinion that termination of pregnancy can be offered at any gestational age.

Conclusion

Both the lay persons as well as the medical fraternity in India feel the need to look into revision of legalisation of LTOP particularly for fetal conditions with poor outcome. Copyright © 2011 John Wiley & Sons, Ltd.
Noninvasive prenatal diagnosis: pregnant women's interest and expected uptake
Authors: Tischler Reana , Hudgins Louanne , Blumenfeld Yair J. , Greely Henry T. , Ormond Kelly E.
Published: October 2011

Objective

To investigate pregnant women's level of future interest in noninvasive prenatal diagnosis (NIPD) and what factors might affect expected uptake of this testing.

Method

Written questionnaires were administered to women in their third trimester.

Results

One hundred fourteen women returned the questionnaire (80.9% response rate). Of these, 71.9% reported interest in NIPD, 22.7% were ambivalent, and 5.4% were uninterested. Safety of the fetus was the single most important factor in 75% of women's decisions. Factors associated with increased interest in NIPD included: older age (p = 0.036), higher education (p = 0.013), Caucasian or Asian ethnicity (p = 0.011), and higher likelihood to terminate an affected pregnancy (p = 0.002). Nearly 20% of women reported that they would do whatever their doctor recommended regarding NIPD, and 94.4% of women wished to meet with a genetic counselor at some point to discuss NIPD.

Conclusion

The majority of pregnant women report hypothetical interest in NIPD, primarily because of increased safety for the fetus, although a significant minority are uninterested or ambivalent. Discussions with healthcare providers regarding NIPD, and their recommendations, are likely to be an important factor in women's decisions about this testing. As such, adequate discussion of the implications of prenatal diagnostic testing will be critical. Copyright © 2011 John Wiley & Sons, Ltd.