bluuebunny/crossref_metadata_2025 huggingface dataset:
Lipid nanoparticle siRNA systems for silencing the androgen receptor in human prostate cancer in vivo
Authors: Lee Justin B. , Zhang Kaixin , Tam Yuen Yi C. , Tam Ying K. , Belliveau Nathan M. , Sung Vanessa Y.C. , Lin Paulo J.C. , LeBlanc Eric , Ciufolini Marco A. , Rennie Paul S. , Cullis Pieter R.
Published: November 2011

The androgen receptor (AR) plays a critical role in the progression of prostate cancer. Silencing this protein using short‐hairpin RNA (shRNA) has been correlated with tumor growth inhibition and decreases in serum prostate specific antigen (PSA). In our study, we have investigated the ability of lipid nanoparticle (LNP) formulations of small‐interfering RNA (siRNA) to silence AR in human prostate tumor cell lines in vitro and in LNCaP xenograft tumors following intravenous (i.v.) injection. In vitro screening studies using a panel of cationic lipids showed that LNPs containing the ionizable cationic lipid 2,2‐dilinoleyl‐4‐(2‐dimethylaminoethyl)‐[1,3]‐dioxolane (DLin‐KC2‐DMA) exhibited the most potent AR silencing effects in LNCaP cells. This is attributed to an optimized ability of DLin‐KC2‐DMA‐containing LNP to be taken up into cells and to release the siRNA into the cell cytoplasm following endocytotic uptake. DLin‐KC2‐DMA LNPs were also effective in silencing the AR in a wild‐type AR expressing cell line, LAPC‐4, and a variant AR expressing cell line, CWR22Rv1. Importantly, it is demonstrated that LNP AR‐siRNA systems containing DLin‐KC2‐DMA can silence AR gene expression in distal LNCaP xenograft tumors and decrease serum PSA levels following i.v. injection. To our knowledge, this is the first report demonstrating the feasibility of LNP delivery of siRNA for silencing AR gene expression in vivo.
Child analysis in a changing world. In the face of a paradigm shift from the mind to the brain: Can we meet the challenge?
Authors: Gauthier Yvon
Published: November 2011

Child analysts and child therapists are now practicing in a new environment where an increased emphasis is made on identifying the symptoms and finding the shortest possible way to get rid of them, from the knowledge of brain functioning. From that perspective, the history of the symptom, of the child who owns it, and of the family in which this child is being raised are not emphasized as strongly. Searching for a specific meaning of such symptoms seems to be of no more interest. How can such a heavy trend be met? Major changes also have occurred within the psychoanalytic milieu. Advances from the observational world, from Spitz (1945) to Bowlby's (1987) attachment theory, provide essential knowledge to the field of early child–parent interactions. Longitudinal research in recent decades has shown close ties between early development and future outcomes. Such new knowledge is inspiring child analysis with very young children as well as with severely disturbed, older children. Early intervention with disadvantaged populations is showing the importance of the nonspecific aspects of the therapeutic relationship as a factor of change. In light of recent neurobiologic research on the influence of a specific environment—attachment experiences—on early development of the brain, it is now possible to speak of the social brain (Cozolino, 2006).
On a heuristic point of view concerning the expression of numerous genes during the cell cycle
Authors: Cooper Stephen
Published: November 2011

The current model of the eukaryotic cell cycle proposes that numerous genes are expressed at different times during the cell cycle. The existence of myriad control points for gene expression leads to theoretical and logical problems for cell cycle control. Each expressed gene requires a control element to appear in a cell‐cycle specific manner; this control element requires another control element and so on, ad infinitum. There are also experimental problems with the current model based on ineffective synchronization methods and problems with microarray measurements of mRNA. Equally important, the efficacy of mRNA variation in affecting changes in protein content is negligible. An alternative view of the cell cycle proposes cycle‐independent, invariant accumulation of mRNA during the cell cycle with decreases of specific proteins occurring only during the mitotic period of the cell cycle. © 2011 IUBMB IUBMB Life, 2011.
Off‐target immune cell toxicity caused by AG‐012986, a pan‐CDK inhibitor, is associated with inhibition of p38 MAPK phosphorylation
Authors: Lee Dong U. , Jessen Bart
Published: November 2011

AG‐012986 is a pan‐CDK (cyclin‐dependent kinase) inhibitor that has in vitro and in vivo antitumor properties but was stopped in development due in part to rapid bone‐marrow‐independent white blood cell toxicity in preclinical studies and the potential for acute and delayed immunosuppression in humans. Because peripheral lymphocytes are largely nonproliferating, it was hypothesized the toxicity of AG‐012986 was due to an off‐target mechanism and not driven by the intended pharmacology. We show the toxicity mechanism in primary human immune cells is caspase driven. T‐cells treated with AG‐012986 and acutely stimulated through the T‐cell receptor exhibited decreased toxicity while still maintaining cell division inhibition. This indicated that the pharmacology of AG‐012986 functioned as expected but the toxicity had now been decoupled through activation. Induced phosphorylation of p38 and IL‐2 production was impaired with AG‐012986. Thus, AG‐012986 could cause apoptosis of T‐cells by targeting upstream kinases in the p38 Mitogen‐activated protein kinase (MAPK) pathway and impairing cellular survival. © 2012 Wiley Periodicals, Inc. J Biochem Mol Toxicol 26:101–108 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.20415
Development, characterization, and applications of a novel estrogen receptor beta monoclonal antibody
Authors: Wu Xianglin , Subramaniam Malayannan , Negron Vivian , Cicek Muzaffer , Reynolds Carol , Lingle Wilma L. , Goetz Matthew P. , Ingle James N. , Spelsberg Thomas C. , Hawse John R.
Published: November 2011

The role of estrogen receptor alpha (ERα) in breast cancer has been studied extensively, and its protein expression is prognostic and a primary determinant of endocrine sensitivity. However, much less is known about the role of ERβ and its relevance remains unclear due to the publication of conflicting reports. Here, we provide evidence that much of this controversy may be explained by variability in antibody sensitivity and specificity and describe the development, characterization, and potential applications of a novel monoclonal antibody targeting full‐length human ERβ and its splice variant forms. Specifically, we demonstrate that a number of commercially available ERβ antibodies are insensitive for ERβ and exhibit significant cross‐reaction with ERα. However, our newly developed MC10 ERβ antibody is shown to be highly specific and sensitive for detection of full‐length ERβ and its variant forms. Strong and variable staining patterns for endogenous levels of ERβ protein were detected in normal human tissues and breast tumors using the MC10 antibody. Importantly, ERβ was shown to be expressed in a limited cohort of both ERα positive and ERα negative breast tumors. Taken together, these data demonstrate that the use of poorly validated ERβ antibodies is likely to explain much of the controversy in the field with regard to the biological relevance of ERβ in breast cancer. The use of the MC10 antibody, in combination with highly specific antibodies targeting only full‐length ERβ, is likely to provide additional discriminatory features in breast cancers that may be useful in predicting response to therapy. J. Cell. Biochem. 113: 711–723, 2012. © 2011 Wiley Periodicals, Inc.
Cross‐talk between endothelial and breast cancer cells regulates reciprocal expression of angiogenic factors in vitro
Authors: Buchanan Cara F. , Szot Christopher S. , Wilson Tia D. , Akman Steven , Metheny‐Barlow Linda J. , Robertson John L. , Freeman Joseph W. , Rylander Marissa Nichole
Published: November 2011

Reciprocal growth factor exchange between endothelial and malignant cells within the tumor microenvironment may directly stimulate neovascularization; however, the role of host vasculature in regulating tumor cell activity is not well understood. While previous studies have examined the angiogenic response of endothelial cells to tumor‐secreted factors, few have explored tumor response to endothelial cells. Using an in vitro co‐culture system, we investigated the influence of endothelial cells on the angiogenic phenotype of breast cancer cells. Specifically, VEGF, ANG1, and ANG2 gene and protein expression were assessed. When co‐cultured with microvascular endothelial cells (HMEC‐1), breast cancer cells (MDA‐MB‐231) significantly increased expression of ANG2 mRNA (20‐fold relative to MDA‐MB‐231 monoculture). Moreover, MDA‐MB‐231/HMEC‐1 co‐cultures produced significantly increased levels of ANG2 (up to 580 pg/ml) and VEGF protein (up to 38,400 pg/ml) while ANG1 protein expression was decreased relative to MDA‐MB‐231 monocultures. Thus, the ratio of ANG1:ANG2 protein, a critical indicator of neovascularization, shifted in favor of ANG2, a phenomenon known to correlate with vessel destabilization and sprouting in vivo. This angiogenic response was not observed in nonmalignant breast epithelial cells (MCF‐10A), where absolute protein levels of MCF‐10A/HMEC‐1 co‐cultures were an order of magnitude less than that of the MDA‐MB‐231/HMEC‐1 co‐cultures. Results were further verified with a functional angiogenesis assay demonstrating well‐defined microvascular endothelial cell (TIME) tube formation when cultured in media collected from MDA‐MB‐231/HMEC‐1 co‐cultures. This study demonstrates that the angiogenic activity of malignant mammary epithelial cells is significantly enhanced by the presence of endothelial cells. J. Cell. Biochem. 113: 1142–1151, 2012. © 2011 Wiley Periodicals, Inc.
Effect of reconstituted discoidal high‐density lipoproteins on lipid mobilization in RAW 264.7 and CHOK1 cells
Authors: Toledo Juan D. , Cabaleiro Laura V. , Garda Horacio A. , Gonzalez Marina C.
Published: November 2011

Reconstituted discoidal high‐density lipoproteins (rHDL) resemble nascent HDL, which are formed at the early reverse cholesterol transport steps, and constitute the initial cholesterol (Chol) acceptors from cell membranes. We have used different sized rHDL containing or not Chol, to test their abilities to promote cholesterol and phospholipid efflux from two different cell lines: Raw 264.7 macrophages and CHOK1 cells. All rHDL and lipid‐free apolipoprotein A‐I (apoA‐I) were found to be bound to CHO and RAW cells. In RAW cells, a positive correlation between cellular binding and Chol removal was found for 78 and 96 Å rHDL. Chol‐free rHDL were more effective than Chol‐containing ones in binding to RAW cells and promoting Chol removal. These results were more evident in the 96 Å rHDL. On the other hand, rHDL binding to CHO cells was relatively independent of disc size and Chol content. In spite of the fact that apoA‐I and rHDL promoted Chol efflux from both cellular lines, only in CHOK1 cells this result was also associated to decrease Chol esterification. Among choline‐containing phospholipids, only phosphatidylcholine (PC) (but not sphingomyelin) was detected to be effuxed from both cellular lines. With the only exception of Chol‐free 96 Å discs, the other rHDL as well as apoA‐I promoted PC efflux from RAW cells. Chol‐containing rHDL were more active than Chol‐free ones of comparable size to promote PC efflux from RAW macrophages. Regarding CHO cells, only apoA‐I and Chol‐free 78 Å rHDL were active enough to remove PC. J. Cell. Biochem. 113: 1208–1216, 2012. © 2011 Wiley Periodicals, Inc.
MiR‐17‐92 cluster regulates cell proliferation and collagen synthesis by targeting TGFB pathway in mouse palatal mesenchymal cells
Authors: Li Ling , Shi Jia‐Yu , Zhu Gui‐Quan , Shi Bing
Published: November 2011

Elongation and elevation of palatal shelves, mainly caused by proliferation and extra‐cellular matrix synthesis of palatal mesenchymal cells (PMCs), are essential for normal palatal development. Transforming growth factor beta (TGFB) pathway could induce proliferation inhibition and collagen synthesis in PMCs. Recent studies found that miRNA‐17‐92 (miR‐17‐92) cluster, including miR‐17, miR‐18a, miR‐19a, miR‐20a, miR‐19b, and miR‐92a, expressed in the 1st bronchial arch of mouse embryos during the period of palatal shelf elongation and elevation, and directly targeted TGFB pathway in cancer cell lines. Whether miR‐17‐92 cluster expresses and targets TGFB pathway in PMCs has not yet been studied. Using quantitative real‐time RT‐PCR, we found that miR‐17‐92 expressed in PMCs and decreased from embryonic day (E) 12 to E14 in palatal shelves. MTT assay and Western blot showed that miR‐17‐92 inhibited TGFB1 induced proliferation inhibition and collagen synthesis in PMCs by decreasing TGFBR2, SMAD2, and SMAD4 protein level. Further luciferase assay showed that miR‐17 and miR‐20a directly targeted 3′UTR of TGFBR2, and that miR‐18a directly targeted 3′UTR of SMAD2 and SMAD4. We thus conclude that miR‐17‐92 cluster could inhibit TGFB pathway induced proliferation inhibition and collagen synthesis in PMCs by directly targeting TGFBR2, SMAD2, and SMAD4. J. Cell. Biochem. 113: 1235–1244, 2012. © 2011 Wiley Periodicals, Inc.
ΔE1 and high‐capacity adenoviral vectors expressing full‐length codon‐optimized merozoite surface protein 1 for vaccination against Plasmodium falciparum
Authors: Zong Shan , Kron Matthias W. , Epp Christian , Engler Tatjana , Bujard Hermann , Kochanek Stefan , Kreppel Florian
Published: November 2011

Background

The merozoite surface protein (MSP)‐1 of Plasmodium falciparum, the causative agent of malaria tropica, is considered to be a promising vaccine candidate. Although its stable cloning and expression has been difficult in the past, adenoviral vectors expressing the complex protein are described in the present study.

Methods

Codon‐optimized msp‐1 was used to construct a set of first generation (ΔE1Ad) and high‐capacity adenovirus (HC‐Ad) vectors, and cellular and humoral immune responses induced by the vectors were characterized in detail in mice.

Results

Generation of stable ΔE1Ad and HC‐Ad vectors expressing full‐length MSP‐1 and their production to high vector titers was found to be feasible. Epitope identification and analysis of frequencies of specific CD8 T‐cells revealed that MSP‐1 expressing HC‐Ad vectors induced higher frequencies of interferon‐γ + CD8 T‐cells than ΔE1 vectors. Irrespective of the vector format, higher titers of MSP‐1 specific antibodies were generated by Ad vectors expressing MSP‐1 from a chicken β‐actin (CAG) promoter comprising the cytomegalovirus early enhancer element and the chicken β‐actin promoter.

Conclusions

The findings of the present study suggest that Ad vectors expressing full‐length codon‐optimized MSP‐1 are promising candidate vaccines against P. falciparum infections. Use of the HC‐Ad vector type for delivery, as well as the CAG promoter to control MSP‐1 expression, may further increase the efficacy of this vaccine candidate. Copyright © 2011 John Wiley & Sons, Ltd.
Detection of liver metastases using gadoxetic‐enhanced dynamic and 10‐ and 20‐minute delayed phase MR imaging
Authors: Jeong Hyeon Tae , Kim Myeong‐Jin , Park Mi‐Suk , Choi Jin‐Young , Choi Jin Sub , Kim Kyung Sik , Choi Gi Hong , Shin Sang‐Joon
Published: November 2011

Purpose:

To assess the incremental value of hepatobiliary phase images in gadoxetate disodium‐enhanced magnetic resonance imaging (MRI), and to compare diagnostic accuracy and lesion conspicuity on 10‐ and 20‐minute delayed images for preoperative detection of hepatic metastases with subgroup analysis according to size and history of chemotherapy.

Materials and Methods:

Forty‐six patients with 107 metastases who underwent surgery after gadoxetate disodium‐enhanced MRI were evaluated. Four observers independently interpreted three sets: dynamic set comprising precontrast T1‐, T2‐weighted, and dynamic images; 10‐minute set comprising dynamic set and 10‐minute delayed; 20‐minute set comprising 10‐minute set and 20‐minute delayed. Diagnostic accuracy was compared with subgroup analysis. Liver‐to‐lesion signal ratio (SR) was calculated using the region of interest method and compared.

Results:

Mean Az and sensitivities were significantly higher for 10‐ (Az = 0.894, sensitivity = 95.6%) and 20‐minute (0.910, 97.2%) than dynamic set (0.813, 79.9%) (P < 0.001), with no significant difference between 10‐ and 20‐minute sets (P = 0.140). In patients with small (≤1 cm) metastases and a history of chemotherapy, sensitivities were significantly higher with 10‐ (88.2%) and 20‐minute (91.6%) sets than dynamic set (48.6%) (P < 0.001). SR was significantly higher for 10‐ and 20‐minute delayed than precontrast and dynamic, with significantly higher SR on 20‐ than 10‐minute delayed.

Conclusion:

Regardless of size or prior chemotherapy, detection of hepatic metastases was significantly improved by adding hepatobiliary phase images without significant differences between 10‐ and 20‐minute delayed. J. Magn. Reson. Imaging 2012;35:635‐643. © 2011 Wiley Periodicals, Inc.
Aortic flow patterns in patients with Marfan syndrome assessed by flow‐sensitive four‐dimensional MRI
Authors: Geiger Julia , Markl Michael , Herzer Lena , Hirtler Daniel , Loeffelbein Florian , Stiller Brigitte , Langer Mathias , Arnold Raoul
Published: November 2011

Purpose:

To apply time‐resolved three‐dimensional (3D) phase contrast MRI with three‐directional velocity encoding (flow‐sensitive 4D MRI) for the characterization of flow pattern changes in patients with Marfan syndrome (MFS) compared with normal controls.

Materials and Methods:

Flow‐sensitive 4D MRI of the thoracic aorta (temporal resolution ∼45 ms, spatial resolution ∼2.4 × 2.1 × 2.8 mm3) was performed in 24 MFS patients and 10 volunteers. Aortic flow patterns were visualized by 3D particle traces and streamlines. Global (affecting the complete lumen) and local (parts of the vessel lumen) helix and vortex flow in the ascending aorta (AAo), aortic arch, and descending aorta (DAo) were graded in 3 categories (blinded reading, two observers): none = 0, moderate = 1, pronounced = 2.

Results:

Flow grading revealed similar global helix and vortex flow in the AAo and arch for MFS patients and controls. Local helix flow in the AAo was significantly (P = 0.011) increased in patients and was associated with aortic sinus dilatation. The incidence of global helix and vortex flow in the DAo was increased in patients (77% and 50% of subjects) compared with controls (none and 10%).

Conclusion:

The 4D flow analysis revealed marked differences of the aortic flow patterns between Marfan patients and controls: Local helix flow in the patients' AAo may be associated with the increased incidence of aortic root dilatation. The flow alterations in the proximal DAo could explain the occurrence of Type‐B dissection originating from this site. J. Magn. Reson. Imaging 2012;35:594‐600. © 2011 Wiley Periodicals, Inc.
Prevalence and impact of hepatitis B and C virus co‐infections in antiretroviral treatment naïve patients with HIV infection at a major treatment center in Ghana
Authors: Sagoe Kwamena William Coleman , Agyei Afrakoma Adjoa , Ziga Francesca , Lartey Margaret , Adiku Theophilus K. , Seshi Makafui , Arens Max Q. , Mingle Julius Abraham Addo
Published: November 2011

Data on the effects of the presence of hepatitis B virus (HBV) and hepatitis C virus (HCV) in patients co‐infected with these viruses and HIV in West Africa are conflicting and little information is available in Ghana. A cohort of 138 treatment naïve individuals infected with HIV was screened for HBV and HCV serologic markers; HBsAg positive patients were tested for HBeAg, anti‐HBe, and anti‐HBc IgM. The viral load of HIV‐1 in the plasma was determined in 81 patients. Eighteen of the 138 patients (13%) and 5 (3.6%) had HBsAg and anti‐HCV, respectively. None of the patients had anti‐HBc IgM, but 10 (55.6%) and 8 (44.4%) of the 18 patients who were HBsAg positive had HBeAg and anti‐HBe, respectively. In patients with measurement of CD4+ undertaken within 1 month (n = 83), CD4+ count was significantly lower in patients with HBeAg (median [IQR], 81 [22–144]) as compared to those with anti‐HBe (median [IQR], 210 [197–222]) (P = 0.002, CI: −96.46 to 51.21). However, those with HIV mono‐infection had similar CD4+ counts (median [IQR], 57 [14–159]) compared to those with HBeAg (P = 1.0, CI: −71.75 to 73.66). Similar results were obtained if CD4+ count was measured within 2 months prior to initiation of HAART (n = 119). Generally, HBV and anti‐HCV did not affect CD4+ and viral loads of HIV‐1 in plasma but patients with HIV and HBV co‐infection who had HBeAg had more severe immune suppression as compared to those with anti‐HBe. This may have implication for initiating HAART in HBV endemic areas. J. Med. Virol. 84:6–10, 2011. © 2011 Wiley Periodicals, Inc.
Mutations within enhancer II and BCP regions of hepatitis B virus in relation to advanced liver diseases in patients infected with subgenotype B3 in Indonesia
Authors: Heriyanto Didik Setyo , Yano Yoshihiko , Utsumi Takako , Anggorowati Nungki , Rinonce Hanggoro Tri , Lusida Maria Inge , Soetjipto  , Triwikatmani Catharina , Ratnasari Neneng , Maduseno Sutanto , Purnama Putut Bayu , Nurdjanah Siti , Hayashi Yoshitake
Published: November 2011

Studies on the characteristics of mutations within the hepatitis B virus (HBV) genome, their roles in the pathogenesis of advanced liver diseases, and the involvement of host properties of HBV‐infected individuals have not been conducted in subgenotype B3‐infected populations. For addressing this issue, 40 cases with HBV surface antigen (HBsAg)—positive advanced liver diseases, including advanced liver cancer and cirrhosis (male 31, female 9, age 54.4 ± 11.6‐year‐old), were collected and compared with 109 cases with chronic hepatitis B (male 71, female 38, age 38.0 ± 13.4‐year‐old). Mutations in enhancer II (Enh II) and basal core promoter (BCP)/precore regions were analyzed by PCR‐direct sequencing method. HBV viral load was examined by real‐time PCR. For all examined regions, the prevalence of mutation was significantly higher in cases with advanced liver diseases. Multivariate analysis showed that, in patients older than 45 years, C1638T and T1753V mutations constituted independent risk factors for the advancement of liver diseases. The presence of C1638T and T1753V mutations may serve as predictive markers for the progression of liver diseases in Indonesia and other countries, where subgenotype B3 infection is prevalent. J. Med. Virol. 84:44–51, 2011. © 2011 Wiley Periodicals, Inc.
BMP‐7 stimulates early diaphyseal fracture healing in estrogen deficient rats
Authors: Blokhuis TJ , Buma P , Verdonschot N , Gotthardt M , Hendriks T
Published: November 2011

Estrogen deficiency causes postmenopausal osteoporosis. The relationship between estrogen deficiency and the high failure rate after osteoporotic fracture treatment is unclear, as is the effect of possible interventions, either with anti‐resorptive agents or with anabolic agents such as bone morphogenetic proteins (BMPs). To investigate the influence of estrogen deficiency as well as the effect of early intervention, forty female wistar rats underwent ovarectomy (OVX) followed by low calcium diet. Ten rats underwent sham operations, followed by normal diet. After 6 weeks, a closed midshaft femoral fracture was induced. Ten animals received a systemic bisphosphonate injection, 10 injection of BMP‐7 in the fracture, and 10 a combination. All then received a normal diet. After 2 weeks healing was evaluated using radiographs, CT, biomechanical testing, and histology. Radiography showed significant increase of bridging in groups treated with BMP‐7. Callus volume was higher in these groups. Bending stiffness and strength were similar between OVX and sham, and not influenced by bisphosphonates. Significant increase was seen in groups treated with BMP‐7. Histology was in accordance with other endpoints. Early fracture healing was not affected by estrogen deficiency. While no beneficiary effect of bisphosphonate treatment was found, injection of BMP‐7 stimulated healing in ovarectomized rats. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:720–725, 2012
An experimental glenoid rim strain analysis for an improved reverse anatomy shoulder implant fixation
Authors: Mordecai Simon C. , Lambert Simon M. , Meswania Jay M. , Blunn Gordon W. , Bayley Ian L. , Taylor Stephen J. G.
Published: November 2011

Loosening of glenoid components in TSA is a main cause of failure. In reverse anatomy TSA designs used for unstable joints, fixation is particularly demanding. Strains developed around the glenoid rim of biomechanical sawbone scapulae implanted with (a) the original fixed‐fulcrum Bayley–Walker glenoid prosthesis in current clinical use, and (b) a revised version with conical cross‐section, were compared. The conical shape of the revised design was hypothesized to produce greater strains in the glenoid rim than the original tapered screw design. The 2D strain field at three accessible locations around the rim of each scapula was measured with three‐element rosette strain gauges for two types of simulated cancellous bone fill under applied physiologically relevant loads. The average strain energy densities around the rim for the conical design were greater than for the original design by a factor of 1.55–2.25 for all loading conditions. Results indicate that a significantly greater proportion of load was directed toward cortical bone in the conical design, thus promoting cortical bone loading. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:998–1003, 2012
Rate coefficients for intramolecular homolytic substitution of oxyacyl radicals at selenium
Authors: Aitken Heather M. , Horvat Sonia M. , Schiesser Carl H. , Lin Ching Yeh , Coote Michelle L.
Published: November 2011

Ab initio and density functional calculations predict that intramolecular homolytic substitution reactions of oxyacyl radicals at the selenium atom in ω‐alkylseleno‐substituted radicals proceed via mechanisms that do not involve hypervalent intermediates. When the leaving radical is tert‐butyl, energy barriers (ΔG‡) for these reactions range from 27.1 (G3(MP2)‐RAD) kJ mol−1 for the formation of the five‐membered cyclic selenocarbonate (6) to 41.5 kJ mol−1 for the six‐membered selenocarbonate (8). G3(MP2)‐RAD calculations predict rate coefficients in the order of 105–108 s−1 and 102–105 s−1 for the formation of 6 and 8, respectively, at 298.15 K in the gas phase. © 2011 Wiley Periodicals, Inc. Int J Chem Kinet 44: 51–58, 2012
Endoscopic anterior cricoid split with balloon dilation in infants with failed extubation
Authors: Horn David L. , Maguire Raymond C. , Simons Jeffrey P. , Mehta Deepak K.
Published: November 2011

Subglottic injury (SGI) is a known complication of prolonged intubation in neonates and infants and can lead to failed extubation. SGI is a spectrum that includes mucosal edema, ulceration, granulation perichondritis, and mature scar formation. Although medical management aimed at treating mucosal edema and extraesophageal reflux is successful in treating a majority of patients, some require surgical intervention to successfully achieve extubation. The surgical options for these patients include tracheostomy, open anterior cricoid split (ACS), and laryngotracheal reconstruction with cartilage grafting. Open ACS is performed through an external incision requiring placement of a drain for a few days. Extubation success rates in the 70% to 80% range have been widely reported. In this article we describe an endoscopic technique for ACS, in which after an endoscopic airway assessment confirms isolated SGI, the cricoid cartilage is divided transluminally with cold steel. Balloon dilation (BD) is then performed with an appropriately sized angiography balloon. We describe preliminary results in which two of three patients were successfully extubated after endoscopic ACS with BD. We believe that this novel technique is a promising alternative to open ACS with similar indications. In addition to the avoidance of a skin incision, endoscopic ACS with BD may enable extubation with comparably shorter lengths of postprocedure intubation than open ACS. Larger series will be required to further establish outcomes of this procedure, including success and complication rates.
Detection of evolving injury to the brachial plexus during transaxillary robotic thyroidectomy
Authors: Luginbuhl Adam , Schwartz Daniel M. , Sestokas Anthony K. , Cognetti David , Pribitkin Edmund
Published: November 2011

Objectives/Hypothesis:

Continuous intraoperative neuromonitoring (IONM) of transcranial electric motor evoked potentials (tceMEPs) and somatosensory evoked potentials (SSEPs) has gained universal acceptance as an efficacious method for detecting emerging positional brachial plexopathy or peripheral nerve compression during spinal and shoulder surgery. This has implications for transaxillary thyroid surgery.

Study Design:

Case report with literature review.

Methods:

The patient underwent robotic transaxillary thyroid surgery with continuous tceMEP and SSEP monitoring of brachial plexus function. We present detailed IONM data depicting the emergence of positional brachial plexopathy.

Results:

Significant amplitude loss of both IONM modalities were identified during an evolving positional plexopathy, which resolved upon upper extremity repositioning and conversion to an open procedure. No permanent nerve injury or deficit was noted following surgery.

Conclusions:

Given the potential for brachial plexus injury during robotic transaxillary thyroid surgery secondary to arm positioning, we recommend that continuous tceMEP and SSEP monitoring be considered during such procedures.
Endoscopic sinus surgery checklist
Authors: Soler Zachary M. , Smith Timothy L.
Published: November 2011

Over 250,000 endoscopic sinus surgeries are performed yearly in the United States alone. Although overall complication rates are low, errors can lead to significant morbidity due to the close proximity of the sinuses to the orbit and skull base and the resultant potential for blindness, cerebrospinal fluid leak, and catastrophic bleeding. Surgical checklists are endorsed by the World Health Organization and have been incorporated into most U.S. operating rooms as a measure to minimize avoidable errors. Standardized surgical checklists were developed with general and/or orthopedic procedures in mind, but in many instances they fail to incorporate concerns specific to endoscopic sinus surgery (ESS). In response to this clinical problem, we sought to develop and institute an ESS surgical checklist. This checklist can serve as a template for physicians who perform ESS and wish to prevent avoidable adverse events.
Thermal Properties of Oligo(2‐ethyl‐2‐oxazoline) Containing Comb and Graft Copolymers and their Aqueous Solutions
Authors: Weber Christine , Krieg Andreas , Paulus Renzo M. , Lambermont‐Thijs Hanneke M. L. , Becer C. Remzi , Hoogenboom Richard , Schubert Ulrich S.
Published: November 2011

Summary: The cationic ring opening polymerization of 2‐ethyl‐2‐oxazoline (EtOx) was applied for the synthesis of methacrylate end‐functionalized well‐defined macromonomers that could be polymerized in a controlled manner using reversible addition‐fragmentation chain transfer polymerization. The obtained comb polymers revealed lower critical solution temperature behavior in aqueous solution. The cloud points of these solutions could be tuned in a range from 35 °C to 85 °C by the incorporation of hydrophobic methyl methacrylate comonomer in varying amounts into the graft copolymers whereas copolymerization with methacrylic acid rendered temperature and pH sensitive copolymers. Thermo‐gravimetric analysis showed a two‐step decomposition of the graft copolymers and differential scanning calorimetry revealed glass transition temperatures that are significantly lowered in comparison to linear PEtOx.
New Photoinitiating Systems for Cationic Polymerization Acting at Near UV and Visible Range
Authors: Aydogan Binnur , Durmaz Yasemin Yuksel , Kahveci Muhammet U. , Uygun Mustafa , Tasdelen M. Atilla , Yagci Yusuf
Published: November 2011

Summary: New photoiniting systems for cationic polymerization acting at near UV and visible range are described. The applicability of acylgermanes as a new class of free radical promoters for photoinitiated cationic polymerization is demonstrated. Moreover, the use of substituted vinyl halides as source for readily oxidizable free radicals is presented. The polymerization of vinyl ethers can be initiated by the irradiation of substituted vinyl halides in the presence of Lewis acids such as zinc halide. Furthermore, possibilities for conducting cationic polymerization at visible range by using highly conjugated thiophene derivatives are demonstrated. Mechanistic aspects of all initiating systems are discussed.
Silicone Nano/Microstructures Obtained in Ionic Polymerization
Authors: Kuźmicz Danuta , Kępczyński Mariusz , Bednar Jan , Mistrikova Veronika , Jachimska Barbara , Nowakowska Maria
Published: November 2011

Summary: This work presents a novel surfactant‐free method of preparation of silicone hollow nano/microstructures in water. New silicone monomer was synthesized by attaching the unsaturated fatty acid ester – methyl 10‐undecenoate (UDM) to the commercial silicone monomer ‐ 1,3,5,7‐tetramethylcyclotetrasiloxane (D) using hydrosilylation reaction. The reaction was catalyzed by Karstedt's catalyst [Pt(0)‐divinyltetramethyldisiloxane complex]. That modified monomer, tetra(11‐methoxy‐11‐oxoundecyl)‐tetramethylcyclotetrasiloxane (D), undergoes self‐organization in water. The anionic ring‐opening polymerization of D resulted in formation of the silicone polymer (poly‐D). Both, the silicone monomer and the polymer were dispersed in aqueous medium using sonication. The structures in the dispersions were visualized by cryo‐transmission electron microscopy (Cryo‐TEM) and optical microscopy. The size of the particles was also determined from dynamic light scattering (DLS) measurements.
Polymer Composites Based on Reactive Carboxylate‐Alumoxanes
Authors: Florjańczyk Zbigniew , Dębowski Maciej , Plichta Andrzej , Ćwil Aleksandra , Affek Marcin , Chwojnowska Elżbieta , Kania Anna
Published: November 2011

Summary: The possibility of applying basic aluminum carboxylates as the cross‐linking monomers in radical polymerization processes as well as the initiators for ATRP of styrene and coordination ROP of heterocyclic monomers was examined. It was established, that aluminum carboxylates containing in their structure the acrylic and lauric acids derivatives show high activity in the copolymerization with vinyl monomers which results in the hybrid polymer networks formation. In the typical ATRP conditions, polymers grafted with styrene are obtained while basic aluminum 2‐bromopropionate is used as the initiator. Hybrid composites i.e. core‐shell nanospheres can be obtained in this way at low degree of polymerization. Nanoparticles of basic aluminum caroboxylates when reacted with triethylaluminum show high activity as initiators in the polymerization processes of ε‐caprolactone, trimethylene carbonate as well as propylene and ethylene oxides. Cross‐linked products in the form of a gel were formed as the result of ROP in such systems. However, linear polymers characterized by Mn above 104 and PDI ≥ 1.9 were obtained after aluminum residuals removal.
Synthesis of Poly (ε‐Caprolactone‐Co‐Tetrahydrofuran) by an Acid Exchanged Montmorillonite Clay
Authors: Bouchama Abdelghani , Ferrahi Mohammed Issam , Belbachir Mohammed
Published: November 2011

Summary: In the present work the copolymerization of ε‐caprolactone with tetrahydrofyran using a proton exchanged Montmorillonite clay as initiator is reported. The effects of the amounts of Mag‐H and the temperature on the synthesis of poly (ε‐caprolactone‐co‐tetrahydrofuran) were studied. The copolymer obtained was characterized by 1H‐NMR spectroscopy.
Molecular alterations in hepatocarcinogenesis induced by dietary methyl deficiency
Authors: Pogribny Igor P. , James S. Jill , Beland Frederick A.
Published: November 2011

A chronic deficiency of major dietary methyl group donors – methionine, choline, folic acid, and vitamin B12 – can induce the development of liver cancer in rodents. Feeding methyl‐deficient diets causes several molecular alterations, including altered lipid metabolism, oxidative stress, deregulated one‐carbon metabolism, and a number of epigenetic abnormalities that result in progressive liver injury culminating in the development of primary liver tumors. Importantly, this methyl‐deficient model of endogenous hepatocarcinogenesis is one of the most relevant models of human liver carcinogenesis that allows studying liver cancer pathogenesis by substantially complementing many shortcomings of humans‐only studies. In this review, we describe molecular changes and their role in pathogenesis of liver carcinogenesis induced by methyl deficiency.
Metabolic syndrome: Evidences for a personalized nutrition
Authors: Perez‐Martinez Pablo , Garcia‐Rios Antonio , Delgado‐Lista Javier , Perez‐Jimenez Francisco , Lopez‐Miranda Jose
Published: November 2011

Both insulin resistance and dyslipidaemia are determined by genetic and environmental factors. Depending on their expression and their function, gene variants may influence either insulin action or other metabolic traits. Nutrition also plays an important role in the development and progression of these conditions. Genetic background may interact with habitual dietary fat composition, affecting predisposition to insulin resistance syndrome and individual responsiveness to changes in dietary fat intake. In this context, nutrigenetics has emerged as a multidisciplinary field focusing on studying the interactions between nutritional and genetic factors and health outcomes. Due to the complex nature of gene–environment interactions, however, dietary therapy may require a “personalized” nutrition approach in the future. Although the results have not always been consistent, gene variants that affect primary insulin action, and particularly their interaction with the environment, are important modulators of glucose metabolism. The purpose of this review is to present some evidence of studies that have already demonstrated the significance of gene–nutrient interactions (adiponectin gene, Calpain‐10, glucokinase regulatory protein, transcription factor 7‐like 2, leptin receptor, scavenger receptor class B type I etc.) that influence insulin resistance in subjects with metabolic syndrome.
Rapid full‐brain fMRI with an accelerated multi shot 3D EPI sequence using both UNFOLD and GRAPPA
Authors: Afacan Onur , Hoge W. Scott , Janoos Firdaus , Brooks Dana H. , Morocz Istvan A
Published: November 2011

The desire to understand complex mental processes using functional MRI drives development of imaging techniques that scan the whole human brain at a high spatial and temporal resolution. In this work, an accelerated multishot three‐dimensional echo‐planar imaging sequence is proposed to increase the temporal resolution of these studies. A combination of two modern acceleration techniques, UNFOLD and GRAPPA is used in the secondary phase encoding direction to reduce the scan time effectively. The sequence (repetition time of 1.02 s) was compared with standard two‐dimensional echo‐planar imaging (3 s) and multishot three‐dimensional echo‐planar imaging (3 s) sequences with both block design and event‐related functional MRI paradigms. With the same experimental setup and imaging time, the temporal resolution improvement with our sequence yields similar activation regions in the block design functional MRI paradigm with slightly increased t‐scores. Moreover, additional information on the timing of rapid dynamic changes was extracted from accelerated images for the case of the event related complex mental paradigm. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.
Simultaneous Determination of Four Sesquiterpenoids in Atractylodes Macrocephala Rhizoma by GC‐FID: Optimisation of an Ultrasound‐assisted Extraction by Central Composite Design
Authors: Shi Yang‐Yang , Guan Shu‐Hong , Tang Ren‐Neng , Tao Si‐Jia , Guo De‐An
Published: November 2011

Introduction

Atractylodes Macrocephala Rhizoma (AMR) is a traditional Chinese medicine containing several sesquiterpenoids with a series of effects. These bioactive compounds may be used as chemical markers for the quality control of AMR. It is necessary to optimise the extraction method and conditions in order to improve extraction productivity.

Objective

To develop a simple and effective method for the extraction of sesquiterpenoids from AMR and then to simultaneously determine four sesquiterpenoids, selina‐4 (14), 7(11)‐dien‐8‐one (SA), atractylenolide II (AII), atractylenolide III (AIII) and atractylenolide VII (AVII), in AMR.

Methodology

Ultrasound‐assisted extraction (UAE) was optimised by central composite design (CCD) to obtain the maximum efficiency. The gas chromatography method was validated and applied for the quantification of four sesquiterpenoids.

Results

The optimum values of factors were: particle size (120 mesh), extraction time (26 min), extraction temperature (39°C) and 31 mL of chloroform. The selectivity, linear range, limits of detection (LOD) and quantification (LOQ), accuracy, precision and repeatability of the method developed indicated its validity. The application of the method showed that the contents of four sesquiterpenoids in AMR were rather variable.

Conclusion

The results indicated that the described GC method could be used for the quality control of AMR and its related preparations. Meanwhile, this research revealed that UAE under optimum conditions could be considered as a powerful tool for the extraction of phytochemicals from plants. Copyright © 2011 John Wiley & Sons, Ltd.
Ribonuclease A suggests how proteins self‐chaperone against amyloid fiber formation
Authors: Teng Poh K. , Anderson Natalie J. , Goldschmidt Lukasz , Sawaya Michael R. , Sambashivan Shilpa , Eisenberg David
Published: November 2011

Genomic analyses have identified segments with high fiber‐forming propensity in many proteins not known to form amyloid. Proteins are often protected from entering the amyloid state by molecular chaperones that permit them to fold in isolation from identical molecules; but, how do proteins self‐chaperone their folding in the absence of chaperones? Here, we explore this question with the stable protein ribonuclease A (RNase A). We previously identified fiber‐forming segments of amyloid‐related proteins and demonstrated that insertion of these segments into the C‐terminal hinge loop of nonfiber‐forming RNase A can convert RNase A into the amyloid state through three‐dimensional domain‐swapping, where the inserted fiber‐forming segments interact to create a steric zipper spine. In this study, we convert RNase A into amyloid‐like fibers by increasing the loop length and hence conformational freedom of an endogenous fiber‐forming segment, SSTSAASS, in the N‐terminal hinge loop. This is accomplished by sandwiching SSTSAASS between inserted Gly residues. With these inserts, SSTSAASS is now able to form the steric zipper spine, allowing RNase A to form amyloid‐like fibers. We show that these fibers contain RNase A molecules retaining their enzymatic activity and therefore native‐like structure. Thus, RNase A appears to prevent fiber formation by limiting the conformational freedom of this fiber‐forming segment from entering a steric zipper. Our observations suggest that proteins have evolved to self‐chaperone by using similar protective mechanisms.
Optical anisotropy of a‐plane Al0.8In0.2N grown on an a‐plane GaN pseudosubstrate
Authors: Sakalauskas E. , Wieneke M. , Dadgar A. , Gobsch G. , Krost A. , Goldhahn R.
Published: November 2011

The optical properties of a‐plane Al1−xInxN grown by metal‐organic vapor phase epitaxy on an a‐plane GaN/r‐plane sapphire template are reported. X‐ray diffraction yielded an In content of ∼20%. The ordinary and extraordinary dielectric functions (DFs) were obtained by spectroscopic ellipsometry in the spectral range from 1 eV up to 6 eV at room temperature. By fitting the experimentally obtained complex DF, the inter‐band transitions EA and EB, which are allowed for configurations ${\bf E}\bot {\bf c}$ and ${\bf E}||{\bf c}$, respectively, were determined. A redshift of ∼200 meV is found for the transition EB with respect to transition EA attributed to the optical selection rules. Furthermore, the ordinary and extraordinary refractive indices in the transparent region (below the band gap) are represented in the analytical form. The AlInN alloy shows the positive birefringence and the difference between the extraordinary and ordinary refractive index ne − no is defined to be 0.068 at photon energy of 3 eV. Finally, the ordinary and extraordinary high‐energy dielectric constants were estimated.
Infrared photoluminescence of high In‐content InN/InGaN multiple‐quantum‐wells
Authors: Valdueza‐Felip Sirona , Rigutti Lorenzo , Naranjo Fernando B. , Lacroix Bertrand , Fernández Susana , Ruterana Pierre , Julien François H. , González‐Herráez Miguel , Monroy Eva
Published: November 2011

We report on the thermal evolution of the photoluminescence (PL) from high In‐content InN/In0.9Ga0.1N multiple‐quantum wells (MQWs) synthesized by plasma‐assisted molecular‐beam epitaxy on GaN‐on‐sapphire templates. The structural quality and the well/barrier thickness uniformity in the MQW structure are assessed by X‐ray diffraction and transmission electron microscopy measurements. PL results are compared with the luminescence from a 1‐µm‐thick InN reference sample. In both cases, the dominant low‐temperature (5 K) PL emission peaks at ∼0.73 eV with a full width at half maximum of ∼86 meV. The InN layer displays an S‐shape evolution of the emission peak energy with temperature, explained in terms of carrier localization. A carrier localization energy of ∼12 meV is estimated for the InN layer, in good agreement with the expected carrier concentration. In the case of the MQW structure, an enhancement of the carrier localization associated to the piezoelectric field results in an improved thermal stability of the PL intensity, reaching an internal quantum efficiency of ∼16%.
Infrared phonon modes and dielectric properties of La2Zr2O7: Comparing thin film to bulk material
Authors: Cheng Xuerui , Qi Zeming , Li Tingting , Zhang Guobin , Li Chengxiang , Zhou Hongjun , Wang Yuyin , Yin Min
Published: November 2011

The infrared phonon modes and dielectric constants of bulk and thin film of La2Zr2O7 are studies by infrared spectroscopy. The infrared response of the La2Zr2O7 bulk sample is determined by seven infrared phonon modes. The obtained static dielectric constant is 22.8 and the largest contribution is from the phonon modes at 213.7 and 352.7 cm−1. Compared to the bulk sample, the obtained dielectric constant of the La2Zr2O7 thin film shows an obvious decrease. The loss of the dielectric constant is due to the absence and weakness of some phonon modes in the thin film, even though it still preserves two important modes, mentioned above. The result indicates that the disorder in the La2Zr2O7 thin film has an important influence on the dielectric property.