bluuebunny/crossref_metadata_2025 huggingface dataset:
The transcriptome of fracture healing defines mechanisms of coordination of skeletal and vascular development during endochondral bone formation
Authors: Grimes Rachel , Jepsen Karl J , Fitch Jennifer L , Einhorn Thomas A , Gerstenfeld Louis C
Published: August 2011

Fractures initiate one round of endochondral bone formation in which callus cells differentiate in a synchronous manner that temporally phenocopies the spatial variation of endochondral development of a growth plate. During fracture healing C57BL/6J (B6) mice initiate chondrogenesis earlier and develop more cartilage than bone, whereas C3H/HeJ (C3H) mice initiate osteogenesis earlier and develop more bone than cartilage. Comparison of the transcriptomes of fracture healing in these strains of mice identified the genes that showed differences in timing and quantitative expression and encode for the variations in endochondral bone development of the two mouse strains. The complement of strain-dependent differences in gene expression was specifically associated with ontologies related to both skeletal and vascular formation. Moreover, the differences in gene expression associated with vascular tissue formation during fracture healing were correlated with the underlying differences in development and function of the cardiovascular systems of these two strains of mice. Significant differences in gene expression associated with bone morphogenetic protein/transforming growth factor β (BMP/TGF-β) signal-transduction pathways were identified between the two strains, and a network of differentially expressed genes specific to the MAP kinase cascade was further defined as a subset of the genes of the BMP/TGF-β pathways. Other signal-transduction pathways that showed significant strain-specific differences in gene expression included the RXR/PPAR and G protein–related pathways. These data identify how bone and vascular regeneration are coordinated through expression of common sets of transcription and morphogenetic factors and suggest that there is heritable linkage between vascular and skeletal tissue development during postnatal regeneration. © 2011 American Society for Bone and Mineral Research
Exact and efficient calculation of lagrange multipliers in biological polymers with constrained bond lengths and bond angles: Proteins and nucleic acids as example cases
Authors: García‐Risueño Pablo , Echenique Pablo , Alonso J. L.
Published: August 2011

To accelerate molecular dynamics simulations, it is common to impose holonomic constraints on the hardest degrees of freedom. In this way, the time step used to integrate the equations of motion can be increased, thereby allowing longer total simulation times. The imposition of such constraints results in an aditional set of Nc equations (the equations of constraint) and unknowns (their associated Lagrange multipliers), whose solution is closely related to any algorithm implementing the constraints in Euclidean coordinates. In this work, it is shown that, due to the essentially linear structure of typical biological polymers the algebraic equations that need to be solved involve a matrix which is not only sparse, but also banded if the constraints are indexed in a skilful way. This allows the Lagrange multipliers to be obtained through a noniterative procedure, which can be considered exact up to machine precision, and which takes O(Nc) operations, instead of the usual O(N) for generic molecular systems. We develop the formalism, and describe the appropriate indexing for a number of model molecules. Finally, we provide a numerical example of the technique in a series of polyalanine peptides of different lengths. Although a use of the Lagrange multipliers without any modification in the solution of the underlying ordinary differential equations yields unstable integration algorithms, the central role of these quantities makes their efficient calculation useful for the improvement of methods that correctly enforce the exact satisfaction of the constraints at each time step. We provide several examples of this. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Bond indices in solids: Extended analytical model
Authors: Ponec Robert
Published: August 2011

The analytical model suggested some time ago for the calculation of bond indices in infinite periodical structures was reconsidered and extended so as to provide not only realistic estimate of the extent of electron sharing localized among individual pairs of the atoms in the lattice but also to detect the eventual presence of multicenter bonding in metallic solids. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Beneficial effects of fenofibrate in retinal pigment epithelium by the modulation of stress and survival signaling under diabetic conditions
Authors: Miranda Soledad , González‐Rodríguez Águeda , García‐Ramírez Marta , Revuelta‐Cervantes Jesús , Hernández Cristina , Simó Rafael , Valverde Ángela M.
Published: August 2011

In this study, we found an imbalance between stress‐mediated and survival signaling and elevated apoptotic markers in retinal pigment epithelium (RPE) from diabetic patients. Since fenofibric acid (FA) treatment reduces the progression of diabetic retinopathy (DR), we investigated the effect of hyperglycemia and hypoxia, two components of the diabetic milieu, on stress, apoptosis, and survival pathways in ARPE‐19 cells (immortalized human RPE cell line) and whether FA is able to prevent the deleterious effects induced by these conditions. ARPE‐19 cells cultured in high‐glucose (HG) medium or under hypoxia (1% oxygen)‐induced phosphorylation of the stress‐activated kinases JNK and p38 MAPK. This effect was increased by the combination of both conditions. Likewise, hyperglycemia and hypoxia triggered the phosphorylation of the endoplasmic reticulum (ER) stress markers PERK and eIF2α and the induction of the pro‐apoptotic transcription factor CHOP. Under these experimental conditions, reactive oxygen species (ROS) were elevated and the integrity of tight junctions was disrupted. Conversely, ARPE‐19 cells treated with FA were protected against these deleterious effects induced by hyperglycemia and hypoxia. FA increased insulin‐like growth factor I receptor (IGF‐IR)‐mediated survival signaling in cells cultured under hyperglycemia and hypoxia, thereby suppressing caspase‐3 activation and down‐regulation of BclxL. Moreover, FA increased LC3‐II, an autophagy marker. In conclusion, our results demonstrated that FA elicits a dual protective effect in RPE by down‐regulation of stress‐mediated signaling and induction of autophagy and survival pathways. These molecular mechanisms could be involved in the beneficial effects of fenofibrate reported in clinical trials. J. Cell. Physiol. 227: 2352–2362, 2012. © 2011 Wiley Periodicals, Inc.
Proliferation of rat small hepatocytes requires follistatin expression
Authors: Ooe Hidekazu , Chen Qijie , Kon Junko , Sasaki Kazunori , Miyoshi Hiroyuki , Ichinohe Norihisa , Tanimizu Naoki , Mitaka Toshihiro
Published: August 2011

Small hepatocytes (SHs) are a subpopulation of hepatocytes that have high growth potential in culture and can differentiate into mature hepatocytes (MHs). The activin (Act)/follistatin (Fst) system critically contributes to homeostasis of cell growth in the normal liver. ActA and ActB consist of two disulfide‐linked Inhibin (Inh)β subunits, InhβA and InhβB, respectively. Fst binds to Act and blocks its bioactivity. In the present study we carried out the experiments to clarify how Fst regulates the proliferation of SHs. The gene expression was analyzed using DNA microarray analysis, reverse transcription‐polymerase chain reaction (RT‐PCR) and real‐time PCR, and protein expression was examined by western blots, immunocytochemistry, and enzyme‐linked immunosorbent assay. RT‐PCR showed that Fst expression was high in SHs and low in MHs. Although the ActA expression was opposite to that of Fst, ActB expression was high in SHs and low in MHs and increased with time in culture. Fst protein was detected in the cytoplasm of SHs and secreted into the culture medium. ActB protein was also secreted into the medium. Although the exogenous administration of ActA and ActB apparently suppressed the proliferation of SHs, apoptosis of SHs was not induced by treatment with ActA or ActB. On the other hand, Fst treatment did not affect the colony formation of SHs but prevented the inhibitory effect of ActA. Neutralization by the anti‐Fst antibody resulted in the suppression of DNA synthesis in SHs, and small hairpin RNA against Fst suppressed the expansion of SH colonies. In conclusion, Fst expression is necessary for the proliferation of SHs. J. Cell. Physiol. 227: 2363–2370, 2012. © 2011 Wiley Periodicals, Inc.
Growth inhibition of human hepatocellular carcinoma cells by overexpression of G‐protein‐coupled receptor kinase 2
Authors: Wei Zhengyu , Hurtt Reginald , Ciccarelli Michele , Koch Walter J. , Doria Cataldo
Published: August 2011

Hepatocellular carcinoma (HCC) is one of the deadliest forms of human liver cancer and does not respond well to conventional therapies. Novel effective treatments are urgently in need. G‐protein‐coupled kinase 2 (GRK2) is unique serine/threonine kinase that involves in many signaling pathways and regulates various essential cellular processes. Altered levels of GRK2 have been linked with several human diseases including cancer. In this study, we investigated a novel approach for HCC treatment by inducing overexpression of GRK2 in human HCC cells. We found that overexpression of GRK2 through recombinant adenovirus transduction inhibits the growth of human HCC cells. BrdU incorporation assay showed that the growth inhibition caused by elevated GRK2 level was due to reduced cell proliferation but not apoptosis. To examine the anti‐proliferative function of increased GRK2 level, we performed cell cycle analysis using propidium iodide staining. We found that the proliferation suppression was associated with G2/M phase cell cycle arrest by the wild‐type GRK2 but not its kinase‐dead K220R mutant. Furthermore, increased levels of wild‐type GRK2 induced upregulation of phosphor‐Ser15 p53 and cyclin B1 in a dose‐dependent manner. Our data indicate that the anti‐proliferative function of elevated GRK2 is associated with delayed cell cycle progression and is GRK2 kinase activity‐dependent. Enforced expression of GRK2 in human HCC by molecular delivery may offer a potential therapeutic approach for the treatment of human liver cancer. J. Cell. Physiol. 227: 2371–2377, 2012. © 2011 Wiley Periodicals, Inc.
PTHrP(1‐34)‐mediated repression of the PHEX gene in osteoblastic cells involves the transcriptional repressor E4BP4
Authors: Pellicelli Martin , Taheri Maryam , St‐Louis Mathieu , Bériault Véronique , Desgroseillers Luc , Boileau Guy , Moreau Alain
Published: August 2011

PHosphate‐regulating gene with homology to Endopeptidase on the X chromosome (PHEX) has been identified as the gene mutated in X‐linked hypophosphatemia (XLH) syndrome, the most prevalent form of rickets in humans. The predominant expression of PHEX in bones and teeth, and the defective mineralization of these tissues in XLH patients indicate that PHEX is an important regulator of mineralization. Parathyroid hormone (PTH) and PTH‐related protein (PTHrP) are known to regulate the expression of numerous genes in osteoblastic cells through activation of the protein kinase A pathway, including repression of PHEX. PTH also activates the transcriptional repressor E4BP4 through the same pathway, suggesting that PTH or PTHrP‐mediated repression of PHEX expression could involve E4BP4. To evaluate this possibility, we treated UMR‐106 osteoblastic cells with PTHrP(1‐34), and used RT‐PCR and immunoblotting to analyze PHEX and E4BP4 expression. E4BP4 mRNA and protein levels were rapidly increased in cells treated with PTHrP(1‐34), with a concomitant decrease in PHEX expression. This downregulation of PHEX could be reproduced by overexpression of E4BP4. Moreover, PTHrP(1‐34)‐mediated PHEX repression was blocked when cells were transfected with a siRNA targeting E4BP4 mRNA. Finally, DNA pull‐down and luciferase assays showed that two E4BP4 response elements located in PHEX promoter were functional. These results underline the important role of E4BP4 in osteoblastic cells and further define the repression mechanism of PHEX gene by PTHrP(1‐34). J. Cell. Physiol. 227: 2378–2387, 2012. © 2011 Wiley Periodicals, Inc.
Diverse effects of type II collagen on osteogenic and adipogenic differentiation of mesenchymal stem cells
Authors: Chiu Li‐Hsuan , Yeh Tien‐Shun , Huang Huei‐Mei , Leu Sy‐Jye , Yang Charng‐Bin , Tsai Yu‐Hui
Published: August 2011

Type II collagen is known to modulate chondrogenesis of mesenchymal stem cells (MSCs). In this study, MSCs from human bone marrow aspirates were used to study the modulating effects of type II collagen on MSC differentiation during the early stages of osteogenesis and adipogenesis. With osteogenic induction, MSCs cultured on the type II collagen‐coated surface showed an enhanced calcium deposition level with increasing mRNA expressions of RUNX2, osteocalcin, and alkaline phosphatase. A synthetic integrin binding peptide, which specifically interacts with the I‐domain of α1β1/α2β1 integrins significantly blocks the mineralization‐enhancing effect of type II collagen. MSCs attached on the type II collagen‐coated plates exhibited expanded cell morphology with increasing spreading area, and the pretreatment of cells with integrin α1β1 or α2β1‐blocking antibody reduced the effect. The phosphorylation levels of FAK, ERK, and JNK significantly increased in the MSCs that attached on the type II collagen‐coated plates. On the contrary, the mineralization‐enhancing effect of type II collagen was diminished by JNK and MEK inhibitors. Furthermore, type II collagen blocked the adipogenic differentiation of MSCs, and this effect is rescued by JNK and MEK inhibitors. In conclusion, type II collagen facilitates osteogenesis and suppresses adipogenesis during early stage MSC differentiation. Such effects are integrin binding‐mediated and conducted through FAK–JNK and/or FAK–ERK signaling cascades. These results inspire a novel strategy encompassing type II collagen in bone tissue engineering. J. Cell. Physiol. 227: 2412–2420, 2012. © 2011 Wiley Periodicals, Inc.
STAT5 isoforms regulate colorectal cancer cell apoptosis via reduction of mitochondrial membrane potential and generation of reactive oxygen species
Authors: Du Wan , Wang Ying‐Chao , Hong Jie , Su Wen‐Yu , Lin Yan‐Wei , Lu Rong , Xiong Hua , Fang Jing‐Yuan
Published: August 2011

Although the two isoforms of signal transducer and activator of transcription 5 (STAT5) protein, STAT5a and STAT5b, have 94% sequence identity, they are encoded by different genes. Previous studies have been unable to define clearly the roles of the STAT5 genes in colorectal cancer (CRC). To investigate the role of STAT5 isoforms in CRC oncogenesis, immunohistochemical staining was performed. Colorectal adenocarcinomas showed higher expression of STAT5a/5b than normal colonic mucosa (P < 0.05), and STAT5b expression was significantly higher than that of STAT5a in colorectal adenocarcinoma tissue (P < 0.05). Furthermore, STAT5b expression was significantly associated with TNM stage. To delineate the roles of STAT5a/5b in CRC carcinogenesis, we studied CRC cells depleted of each isoform by treating the cells with small interfering RNA. Both STAT5a and STAT5b were found to be involved in cell growth, cell cycle progression, and apoptosis of CRC cells, and exerted their effects via the regulation of downstream targets of the STAT genes. However, STAT5b influenced CRC cell apoptosis more than STAT5a (P < 0.05), reducing mitochondrial membrane potential and generating reactive oxygen species. In conclusion, both isoforms of STAT5 are involved in the growth and cell cycle progression of CRC cells, STAT5b could play a more important role than STAT5a in the clinicopathological characteristics of CRC and CRC cell apoptosis. J. Cell. Physiol. 227: 2421–2429, 2012. © 2011 Wiley Periodicals, Inc.
Retinoic acid modulates chondrogenesis in the developing mouse cranial base
Authors: Kwon Hyuk‐Jae , Shin Jeong‐Oh , Lee Jong‐Min , Cho Kyoung‐Won , Lee Min‐Jung , Cho Sung‐Won , Jung Han‐Sung
Published: August 2011

The retinoic acid (RA) signaling pathway is known to play important roles during craniofacial development and skeletogenesis. However, the specific mechanism involving RA in cranial base development has not yet been clearly described. This study investigated how RA modulates endochondral bone development of the cranial base by monitoring the RA receptor RARγ, BMP4, and markers of proliferation, programmed cell death, chondrogenesis, and osteogenesis. We first examined the dynamic morphological and molecular changes in the sphenooccipital synchondrosis‐forming region in the mouse embryo cranial bases at E12–E16. In vitro organ cultures employing beads soaked in RA and retinoid‐signaling inhibitor citral were compared. In the RA study, the sphenooccipital synchondrosis showed reduced cartilage matrix and lower BMP4 expression while hypertrophic chondrocytes were replaced with proliferating chondrocytes. Retardation of chondrocyte hypertrophy was exhibited in citral‐treated specimens, while BMP4 expression was slightly increased and programmed cell death was induced within the sphenooccipital synchondrosis. Our results demonstrate that RA modulates chondrocytes to proliferate, differentiate, or undergo programmed cell death during endochondral bone formation in the developing cranial base. J. Exp. Zool. (Mol. Dev. Evol.) 316:574–583, 2011. © 2011 Wiley Periodicals, Inc.
Synthesis and characterization of scVEGF‐PEG‐[68Ga]NOTA and scVEGF‐PEG‐[68Ga]DOTA PET tracers
Authors: Blom Elisabeth , Velikyan Irina , Monazzam Azita , Razifar Pasha , Nair Manoj , Razifar Payam , Vanderheyden Jean‐Luc , Krivoshein Arcadius V. , Backer Marina , Backer Joseph , Långström Bengt
Published: August 2011

Vascular endothelial growth factor (VEGF) signaling via vascular endothelial growth factor receptor 2 (VEGFR‐2) on tumor endothelial cells is a critical driver of tumor angiogenesis. Novel anti‐angiogenic drugs target VEGF/VEGFR‐2 signaling and induce changes in VEGFR‐2 prevalence. To monitor VEGFR‐2 prevalence in the course of treatment, we are evaluating 68Ga positron emission tomography imaging agents based on macrocyclic chelators, site‐specifically conjugated via polyethylene glycol (PEG) linkers to engineered VEGFR‐2 ligand, single‐chain (sc) VEGF. The 68Ga‐labeling was performed at room temperature with NOTA (2,2′,2′′‐(1,4,7‐triazonane‐1,4,7‐triyl) triacetic acid) conjugates or at 90 °C by using either conventional or microwave heating with NOTA and DOTA (2,2′,2′′,2′′′‐(1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetrayl) tetraacetic acid) conjugates. The fastest (~2 min) and the highest incorporation (>90%) of 68Ga into conjugate that resulted in the highest specific radioactivity (~400 MBq/nmol) was obtained with microwave heating of the conjugates. The bioactivity of the NOTA‐ and DOTA‐containing tracers was validated in 3‐D tissue culture model of 293/KDR cells engineered to express high levels of VEGFR‐2. The NOTA‐containing tracer also displayed a rapid accumulation (~ 20 s after intravenous injection) to steady‐state level in xenograft tumor models. A combination of high specific radioactivity and maintenance of functional activity suggests that scVEGF‐PEG‐[68 Ga]NOTA and scVEGF‐PEG‐[68 Ga]DOTA might be promising tracers for monitoring VEGFR‐2 prevalence and should be further explored. Copyright © 2011 John Wiley & Sons, Ltd.
Neuroprotection by rosiglitazone in transient focal cerebral ischemia might not be mediated by glutamate transporter‐1#
Authors: Verma Rajkumar , Mishra Vikas , Gupta Konica , Sasmal Dinakar , Raghubir Ram
Published: August 2011

Glutamate transport represents a key mechanism for maintaining low level of glutamate in the extracellular milieu to restrict the excitotoxic action of glutamate released during ischemia/reperfusion (I/R) injury. Recently, it has been reported that glutamate transporter‐1 (GLT‐1) is a novel target for peroxisome proliferator‐activated receptor‐γ (PPARγ) agonist, which shows neuroprotection following oxygen glucose deprivation (OGD) in neuronal–astrocytic cocultures. Hence, the present study was undertaken to investigate the role of rosiglitazone in neuroprotection mediated by GLT‐1 following focal cerebral I/R injury in rat. We found that rosiglitazone (2 mg/kg i.p) administered pre‐ or post‐I/R injury significantly improved behavioral outcome and decreased cerebral infarct volume. However, no significant changes were observed in GLT‐1 mRNA and protein expression in rosiglitazone‐treated rats following 1 hr of ischemia/24 hr of reperfusion (1/24 hr I/R) injury. Interestingly, bioinformatics analysis also does not reveal any PPAR response element on the GLT‐1/EAAT2 promoter region. Further rosiglitazone neither increased [3H]glutamate uptake in glia‐enriched preparations nor caused any change in glutamine synthetase activity. On the other hand, there was a significant (P < 0.05) downregulation in tumor necrosis factor‐α and interleukin‐1β gene expression, which were more pronounced in the posttreatment group. The posttreatment with rosiglitazone also significantly reduced the increase in prostaglandin E2 level in the ischemic brain. Therefore, the present findings suggest that the neuroprotective effect of rosiglitazone does not seem to be mediated by modulation of GLT‐1 protein expression/activity in a focal cerebral ischemia model. However, the results do provide increasing evidence that the neuroprotective effect may be mediated by its antiinflammatory action. © 2011 Wiley‐Liss, Inc.
Sirt1 overexpression in neurons promotes neurite outgrowth and cell survival through inhibition of the mTOR signaling
Authors: Guo Wenjing , Qian Lei , Zhang Jing , Zhang Wei , Morrison Alastair , Hayes Philip , Wilson Steve , Chen Tongsheng , Zhao Jie
Published: August 2011

The mammalian nicotinamide‐adenine dinucleotide (NAD)‐dependent deacetylase Sirt1 impacts different processes involved in the maintenance of brain integrity and in the pathogenic pathways associated with several neurodegenerative disorders, including Alzheimer's disease. Here we used human Sirt1 transgenic mice to demonstrate that neuron‐specific Sirt1 overexpression promoted neurite outgrowth and improved cell viability under normal and nutrient‐limiting conditions in primary culture systems and that Sirt1‐overexpressing neurons exhibited higher tolerance to cell death or degeneration induced by amyloid‐β1–42 oligomers. Coincidentally, we found that enhanced Sirt1 expression in neurons downregulated the mammalian target of rapamycin (mTOR) protein levels and its phosphorylation without changes in its mRNA levels, which was accompanied by concomitant inhibition of the mTOR downstream signaling activity as revealed by decreased p70S6 kinase (p70S6K) phosphorylation at Thr389. Consistently with this, using a Sirt1 siRNA transfection approach, we observed that reduction of endogenous mouse Sirt1 led to increased levels of mTOR and phosphorylation of itself and p70S6K as well as impaired cell survival and neurite outgrowth in wild‐type mouse primary neurons, corroborating a suppressing effect of mTOR by Sirt1. Correspondingly, the mTOR inhibitor rapamycin markedly improved neuronal cell survival in response to nutrient deprivation and significantly enhanced neurite outgrowth in wild‐type mouse neurons. The protective effect of rapamycin was extended to neurons even with Sirt1 siRNA knockdown that displayed developmental abnormalities compared with siRNA control‐treated cells. Collectively, our findings suggest that Sirt1 may act to promote growth and survival of neurons in the central nervous system via its negative modulation of mTOR signaling. © 2011 Wiley‐Liss, Inc. © 2011 Wiley‐Liss, Inc.
In situ cosmogenic exposure ages from the Isle of Skye, northwest Scotland: implications for the timing of deglaciation and readvance from 15 to 11 ka
Authors: Small David , Rinterknecht Vincent , Austin William , Fabel Derek , Miguens‐Rodriguez Maria , xu Sheng
Published: August 2011

We present 10 in situ cosmogenic exposure ages from two moraines on the Isle of Skye. The Strollamus medial moraine was deposited during deglaciation of the Devensian ice sheet and yields a mean exposure age from five samples of 14.3 ± 0.9 ka. The moraine age indicates that a significant ice mass existed on Skye at the time of a regional readvance recorded in Wester Ross, northwest Scotland. Taken at face value the ages suggest that deglaciation did not occur until well into Greenland Interstade 1. The Slapin moraine represents the local limit of the Loch Lomond Readvance (LLR) and yields a mean exposure age from five samples of 11.5 ± 0.7 ka, which is consistent with deposition relating to the LLR. These ages suggest that the maximum extent may have been reached late in the stadial and that some glaciers may have remained active until after the climatic amelioration that marks its end. This scenario is considered unlikely given the nature of the climate during this period, which leads us to call for a locally calibrated production rate. Copyright © 2011 John Wiley & Sons, Ltd.
Holocene migration of oceanic front systems over the Conrad Rise in the Indian Sector of the Southern Ocean
Authors: Katsuki Kota , Ikehara Minoru , Yokoyama Yusuke , Yamane Masako , Khim Boo‐Keun
Published: August 2011

There has been limited previous research about Holocene climate variability in the Indian Sector of the Southern Ocean. Here we examine centennial‐scale changes in diatom assemblages and stable isotopic ratios since 10 000 cal a BP in a high‐accumulation‐rate sediment core from the Conrad Rise. Although abundances of dominant diatom taxa (Fragilariopsis kerguelensis and Thalassiothrix antarctica) are comparatively constant, relative abundances of secondary taxa fluctuate. Before c. 9900 cal a BP, winter sea‐ice and cold water covered the Conrad Rise. Following deglaciation the sea‐ice retreated from the Conrad Rise, lagging that of the Atlantic and eastern Indian Sectors by about 1500 a. The Polar Front moved southward during the early Holocene optimum and north Antarctic Zone waters covered the Conrad Rise for about 650 a. After 9300 cal a BP, solar insolation strongly influenced sea surface temperature and primary productivity in the Southern Ocean. In the high‐latitude Indian Sector, productivity increased 1500 a after the onset of late Holocene neoglaciation. Periodic δ18O and cold‐water diatom taxa spikes (at intervals of 200 and 300–500 a, respectively) occurred after 9300 cal a BP, probably associated with solar activity. Fluctuations in short‐term sea surface temperature and cold‐water taxa are synchronous with changes in δD observed in an east Antarctic ice core. Copyright © 2011 John Wiley & Sons, Ltd.
Allelic loss of susceptibility loci and the occurrence of BRAF and RAS mutations in patients with familial non‐medullary thyroid cancer
Authors: Na Kuk Young , Kim Ra Mi , Song Eun‐Mi , Lee Ji Hyun , Lee Jandee , Soh Euy‐Young
Published: August 2011

Objectives

Approximately 5% of non‐medullary thyroid cancer (NMTC) diagnoses are made against a background of familial predisposition and, in such instances, the disease is termed familial non‐medullary thyroid cancer (FNMTC). To date, neither genetic alterations causing FNMTC nor genes predisposing to the condition have been described. The objective of the present study was to evaluate loss of heterozygosity (LOH) at the four known susceptibility loci (fPTC/PRN, NMTC1, MNG1, and TCO1) and to compare the mutation rates of RAS/RAF genes in patients with FNMTC and sporadic NMTC.

Methods

Fourteen FNMTCs in patients from seven families were analyzed in terms of involvement of the four susceptibility loci, and 63 thyroid cancer tumors [FNMTC (29) and NMTC (34)] were evaluated for the occurrence of mutations in BRAF, and H‐, N‐, and K‐RAS, using polymerase chain reaction, single‐strand conformation polymorphism (PCR‐SSCP) analysis, and direct sequencing.

Results

Only five (35.7%) tumors showed loss of LOH at the three susceptibility loci (NMTC1, MNG1, or TCO1). These allelic losses did not show a specific pattern. Four (13.8%) FNMTCs and one (2.9%) NMTC had H‐RAS (codon 12) mutations. Further, mutation of BRAF V600E was observed in 12 (41.4%) FNMTCs and 29 (85.3%) NMTCs.

Conclusion

Four known susceptibility loci are infrequently involved in FNMTC. Although further studies are needed, the present findings additionally suggest that somatic activation of oncogenes via BRAF and RAS mutation plays a role in FNMTC tumorigenesis. J. Surg. Oncol. 2012; 105:10–14. © 2011 Wiley Periodicals, Inc.
Multidisciplinary head and neck cancer clinic and adherence with speech pathology
Authors: Starmer Heather , Sanguineti Giuseppe , Marur Shanthi , Gourin Christine G.
Published: August 2011

Objectives:

To determine the effect of referral patterns on compliance with speech–language pathology (SLP) treatment of voice and swallowing difficulties in patients with head and neck cancer (HNCA).

Study Design:

Retrospective cohort study.

Methods:

Patients with newly diagnosed oropharyngeal HNCA referred for pretreatment SLP evaluation comprised the study population. Compliance was measured by participation in SLP therapy during and after head and neck treatment, as well as by the number of missed and completed visits. Outcomes were compared between patients who were initially evaluated through the multidisciplinary clinic and those evaluated outside of the multidisciplinary clinic format.

Results:

The final study sample included 118 individuals with oropharyngeal tumors. All patients were treated with primary radiotherapy with or without chemotherapy. Patients evaluated initially through the multidisciplinary clinic had more SLP visits than those who did not participate in the multidisciplinary clinic (mean = 1.8 vs. 0.2, P <.0001). Participation in SLP treatment was significantly greater for patients ≥60 years of age (odds ratio [OR] = 2.4, P =.032) and for patients who participated in the multidisciplinary clinic (OR = 19.3, P <.0001). Tumor stage, sex, race, marital status, and insurance status were not associated with patient compliance. Multivariate analysis revealed that participation in a multidisciplinary clinic was the only significant variable associated with SLP treatment compliance (OR = 12.9, P <.0001), after controlling for all other variables.

Conclusions:

Patients evaluated in a multidisciplinary clinic are more likely to comply with SLP treatment recommendations.
Congenital choristomas of the oral cavity in children
Authors: Chai Raymond L. , Ozolek John A. , Branstetter Barton F. , Mehta Deepak K. , Simons Jeffrey P.
Published: August 2011

Objectives/Hypothesis:

To review our institutional experience with oral cavity choristomas in children.

Study Design:

Retrospective case series and medical record review.

Methods:

Medical records including clinic notes, operative reports, radiologic studies, and pathology specimens were reviewed. All imaging studies and pathology material were reviewed by a head and neck radiologist and pediatric pathologist, respectively.

Results:

Sixteen patients (10 males and 6 females) with congenital oral cavity choristomas were identified. Mean age at diagnosis was 1.8 months. Location of the lesions included tongue (n = 9) and floor of mouth (n = 7). Preoperative imaging included magnetic resonance imaging (n = 6), computed tomography (n = 5), plain radiography (n = 1), and no imaging (n = 4). Radiographically, the lesions were consistently lobular with well‐defined margins, but other imaging features often mimicked other masses that can arise in the tongue and floor of mouth. Symptoms were present in five of 16 patients and included difficulty feeding, swelling with upper respiratory infection, and partial airway obstruction. Complete surgical excision was performed in 15 of 16 patients; mean age at the time of surgery was 12.7 months. One patient underwent marsupialization. No complications were noted perioperatively. No recurrences of choristoma were seen. On histologic examination, the predominant component was cystic with cyst linings of respiratory epithelium (n = 5), gastric (foveolar) epithelium (n = 1), or both (n = 10).

Conclusions:

This study supports surgical excision as an effective intervention for children with oral cavity choristomas. Because the etiology of these cysts is unknown and diagnostic terminology is widely variable, we propose a more descriptive diagnosis based on the histology (i.e., lingual choristoma [or lingual developmental cyst] with respiratory epithelium or lingual choristoma [or lingual developmental cyst] with gastric epithelium).
The effect of heat treatment on superconductivity of Zn‐doped YBa2Cu3‐xZnxO7‐y
Authors: Xue Z. , Fu H. , Dong A. , Che G. , Wang Y.
Published: August 2011

YBa2Cu3‐xZnxO7‐y compounds with x = 0, 0.05, 0.15, and 0.30 have been synthesized by standard solid state reaction method. The crystal structure, lattice parameters, and oxygen content are not changed by the substitution of Zn for Cu since both valence state and ionic radius are almost identical for Zn and Cu elements in YBa2Cu3‐xZnxO7‐y. However, the superconducting transition temperature Tc decreases with the increase of Zn content, reflecting the Tc‐suppression effect of Zn substitution. Heat treatment experiments indicate that the heat treatment at low temperature is beneficial to improve the superconductivity of the sample. But Tc decreases with the increase of annealing temperature when the treatment temperature is above 300°C, and finally the superconductivity disappears at approximately 920°C, 700°C and 550°C for the samples with x = 0.0, 0.05 and 0.15, respectively. Our experiments indicate that the superconductivity of the sample with higher Zn content is more sensitive to the oxygen content, and a small decrease in the oxygen content can lead to a considerable decrease of Tc.
Erosion mechanisms of aluminium nitride ceramics at different impact angles
Authors: Grilec K. , Ćurković L. , Kumić I. , Baršić G.
Published: August 2011

In this paper, erosion wear behaviour of aluminium nitride (AlN) ceramics is studied. The influence of particle hardness and shape on erosion of the AlN surface is examined. The effect of varying the impingement angle on the weight loss and the roughness parameters of AlN ceramics testing sample is also determined. Therefore, erosive wear behaviour of AlN ceramics was investigated using SiC and SiO2 particles as erodents, at following impact angles: 30°, 45°, 60°, 75° and 90°. Scanning electron microscopy (SEM) was used to analyze the eroded surfaces in order to determine erosion mechanisms. The roughness parameters (Ra, Rz and Rmax), before and after erosion with SiO2 and SiC particles at 30° and 90° angles of impingement, respectively, were determined using a profilometer. It was found that the impact angle is influencing the erosion wear of the AlN ceramics and maximum erosion takes place at impact angle of 90°. The results indicate that hard, angular SiC particles cause more damage than softer, more rounded SiO2 particles.
Effects of type of shielding gas upon local mechanical properties of laser welded joint in heat‐treatable steel
Authors: Bauer B. , Kralj S. , Kožuh Z. , Dorn L.
Published: August 2011

Small additions of oxygen or carbon dioxide to argon shielding at laser beam welding can increase welding speed and productivity and decrease the mechanical properties of welded joints. The effect of the type of active shielding gas mixtures based on argon with additions of oxygen and/or carbon dioxide upon the local mechanical properties of laser welded joints of heat‐treatable steel 25 CrMo 4 was studied. Microshear test method has been used to investigate the local mechanical properties of welded joints, including microshear strength, microshear plasticity and microshear thoughness. The obtained data were statistically processed, and a mathematical modeling of mechanical properties applying the method of response surfaces was carried out. The analysis revealed that the impact of the used shielding gas mixtures upon the local mechanical properties of the joint is not very significant. The results indicate that the microshear test can be used successfully for estimation of the local mechanical properties distribution of laser welded joints.
Assessment of sharply notched specimens under high mean stress by means of the local‐strain‐approach
Authors: Schneider R. , Wuttke U. , Berger C.
Published: August 2011

Im vorliegenden Beitrag wird aufbauend auf dem Örtlichen Konzept ein Bewertungsverfahren erläutert, mit dem sich die Schwingfestigkeit scharf gekerbter Bauteile unter hoher Mittelspannung rechnerisch abschätzen lässt. Die Erweiterung des Konzeptes besteht im Wesentlichen in der Berücksichtigung der zyklischen Spannungsrelaxation im Kerbgrund. Die Beschreibung des Konzeptes erfolgt anhand einer klassischen Schraube‐Mutterverbindung, die ein sehr gutes Beispiel für zyklisch beanspruchte Bauteile bei hohen Mittellasten ist. Eine Überleitung der Örtlichen Bewertung auf das im Allgemeinen bei Schrauben angewendete Nennspannungskonzept erfolgt am Beispiel der kombinierten Biege‐ und Axialbeanspruchung.
Effect of the geometry on the description of the water absorption by composite materials using diffusion models
Authors: da Silva W. P. , e Silva C. M. D. P. S. , Farias V. S. O. , Lima A. G. B.
Published: August 2011

In this paper, the influence of the geometric representation of samples of a composite material on the description of its water absorption is studied. It is supposed that diffusion models with boundary condition of the first kind satisfactorily describe the absorption, and that the volume and effective mass diffusivity are constant during the process. The geometries used to represent the samples are: infinite slab, rectangular plate and parallelepiped. The effective mass diffusivity is determined by coupling of the analytical solution corresponding to the model to an optimizer based on the inverse method. For the dimensions of the samples, based on statistical indicators obtained in the simulation of each model, it can be concluded that the best geometric representation is the parallelepiped. However, if there is no interest about the moisture distribution within the sample and the only objective of the research is to describe the water absorption kinetics, the infinite slab can also be used.
Melting and glass transition as mixing processes
Authors: Hoffmann H.‐J.
Published: August 2011

Melting of chemically bonded solids has been explained recently by transitions of electrons in higher electron states. Such transitions are shown to cause decomposition of the crystals into many units or sub‐systems build‐up of one or few atoms that mix in the melt. Most chemical elements possess molar melting entropies, ΔSm, in the order of the universal molar gas constant, R, or less, which is expected for mixing of a small number of differing groups of particles totalling one mole. Only in the case of crystals with bonding via sp3‐ and similar hybrids the molar melting entropy is much larger. This observation can be interpreted by a massive change of the phonon spectra of the melting solids in addition to the decomposition into mixing units. Upon cooling the melt below the glass transition temperature, Tg, the mixed decomposition products of the melt are frozen in. This frozen‐in mixing entropy cannot be removed from the undercooled melt and – finally – the glass by thermal conduction and remains stored in the glass until the absolute zero of the temperature. Removal of the mixing entropy is possible only by reordering of the constituents or crystallisation. Since the entropy is frozen‐in near and above Tg not only entropy but also enthalpy is frozen‐in, which is often neglected in the literature. The specific amounts of the entropy and enthalpy frozen‐in are not unique for a given glass but depend on the status of relaxation.
Respiratory diseases in Greater Buenos Aires and meteorological variables
Authors: Alessandro Adelia P.
Published: August 2011

This paper provides a preliminary assessment of the relationship between atmospheric conditions and respiratory diseases based on the analysis of disease occurrence in patients during the period August 2004 to September 2007. To this effect, medical records from a medical services firm were examined, as well as temperature data (daily, maximum, minimum, dew point), pressure and relative humidity, measured at the meteorological station of Ezeiza (34.49°S, 58.32°W). The analysis revealed a strong seasonal relationship, with a peak in winter (low temperatures) and a minimum in summer. The annual cycle explains 76.24% of the total of the variance of the series. Most patients were below 10 years of age and older than 71. The best correlations were observed between daily values of the number of patients presenting with disease symptoms (N) and temperature, and between monthly values of N and maximum temperature (coefficients of − 0.73 and − 0.91, respectively). Multiple correlation between all meteorological variables obtained with the Stepwise method, made it possible to estimate the expected number of patients on daily and monthly scales. Mean geopotential height fields at 1000 hPa corresponding to days with the lowest number of patients have opposite synoptic characteristics to those of days with the largest number of patients. The same occurs with the fields corresponding to consecutive days with less than 40 patients per day and consecutive days with more than 300 patients per day. The fields corresponding to extremely high values show a positive pressure anomaly and consequent cold air advection over Buenos Aires and surrounding areas. Copyright © 2011 Royal Meteorological Society
Verification of the ECMWF ensemble forecasts of wind speed against analyses and observations
Authors: Pinson Pierre , Hagedorn Renate
Published: August 2011

A framework for the verification of ensemble forecasts of near‐surface wind speed is described. It is based on existing scores and diagnostic tools, though considering observations from synoptic stations as reference instead of the analysis. This approach is motivated by the idea of having a user‐oriented view of verification, for instance with the wind power applications in mind. The verification framework is specifically applied to the case of ECMWF ensemble forecasts and over Europe. Dynamic climatologies are derived at the various stations, serving as a benchmark. The impact of observational uncertainty on scores and diagnostic tools is also considered. The interest of this framework is demonstrated from its application to the routine evaluation of ensemble forecasts and to the assessment of the quality improvements brought in by the recent change in horizontal resolution of the ECMWF ensemble prediction system. The most important conclusions cover (1) the generally high skill of these ensemble forecasts of near‐surface wind speed when evaluated at synoptic stations, (2) the noteworthy improvement of scores brought by the change of horizontal resolution, and, (3) the scope for further improvements of reliability and skill of wind speed ensemble forecasts by appropriate post‐processing. Copyright © 2011 Royal Meteorological Society
Stimulation of erythrocyte phospholipid scrambling by enniatin A
Authors: Jilani Kashif , Qadri Syed M. , Lang Elisabeth , Zelenak Christine , Rotte Anand , Bobbala Diwakar , Lang Florian
Published: August 2011

Scope: Enniatin A, a peptide antibiotic and common food contaminant, triggers mitochondrial dysfunction and apoptosis. Even though lacking mitochondria, erythrocytes may similarly undergo suicidal cell death or eryptosis. Eryptosis is characterized by cell shrinkage and cell membrane phospholipid scrambling. Triggers of phospholipid scrambling include energy depletion and increase in cytosolic Ca2+ activity ([Ca2+]i). The present study explored whether enniatin A triggers phospholipid scrambling.

Methods and results: Phospholipid scrambling was estimated from annexin‐V‐binding, cell volume from forward scatter (FSC), [Ca2+]i from Fluo3‐fluorescence, cytosolic ATP‐concentration ([ATP]i) using a luciferase assay and hemolysis from hemoglobin release. Exposure of erythrocytes for 48 h to enniatin A (≥2.5 μM) significantly increased [Ca2+]i, decreased [ATP]i, decreased FSC, triggered annexin‐V‐binding and elicited hemolysis. Annexin‐V‐binding affected 25%, and hemolysis 2% of treated erythrocytes. Decreased [ATP]i by glucose depletion for 48 h was similarly followed by increased [Ca2+]i, decreased FSC and annexin‐V‐binding. Enniatin A augmented the effect on [Ca2+]i and annexin‐V‐binding, but not on FSC. Annexin‐V‐binding was blunted by Ca2+ removal, by the cation channel inhibitor amiloride (1 mM), by the protein kinase C inhibitor staurosporine (500 nM) but not by the pancaspase inhibitor zVAD (10 μM).

Conclusion: The food contaminant enniatin A triggers ATP depletion and increases cytosolic Ca2+ activity, effects resulting in suicidal erythrocyte death.
Soy food supplementation, dietary fat reduction and peripheral blood gene expression in postmenopausal women – A randomized, controlled trial
Authors: Wang Jun , Siegmund Kimberly , Tseng Chiu‐Cheng , Lee Amy S. , Wu Anna H.
Published: August 2011

Scope: The effect of soy food supplementation or dietary fat reduction on gene expression is not well studied.

Methods and results: We evaluated the potential of gene expression profiling in peripheral blood mononuclear cells (PBMCs) collected at baseline and at the completion of an 8‐wk controlled dietary intervention. Healthy postmenopausal women were randomized to a very‐low‐fat diet (VLFD; 11% of energy as fat) (n=21), a Step 1 diet (25% energy as fat) supplemented with soy food (SFD; 50 mg isoflavones per day) (n=20), or a control Step 1 diet (CD; 27% energy as fat) with no SFD (n=18). All diets were prepared at the General Clinical Research Center of the University of Southern California. We did not observe any gene that showed variable response across the three dietary interventions. However, there were notable changes in gene expression associated with the intervention in the VLFD and SFD groups. Our findings suggest that the expression of nicotinamide phosphoribosyltransferase (NAMPT) and genes related to Fc γ R‐mediated phagocytosis and cytokine interactions may be significantly altered in association with dietary fat reduction and soy supplementation. Gene expression changes in NAMPT were somewhat dampened with adjustment for weight but changes related to Fc γ R‐mediated phagocytosis and cytokine interactions remained largely unchanged.

Conclusion: PBMCs can reveal novel gene expression changes in association with controlled dietary intervention.