bluuebunny/crossref_metadata_2025 huggingface dataset:
Carbon nanotube-clamped metal atomic chain
Authors: Tang Dai-Ming , Yin Li-Chang , Li Feng , Liu Chang , Yu Wan-Jing , Hou Peng-Xiang , Wu Bo , Lee Young-Hee , Ma Xiu-Liang , Cheng Hui-Ming
Published: April 2010

Metal atomic chain (MAC) is an ultimate one-dimensional structure with unique physical properties, such as quantized conductance, colossal magnetic anisotropy, and quantized magnetoresistance. Therefore, MACs show great potential as possible components of nanoscale electronic and spintronic devices. However, MACs are usually suspended between two macroscale metallic electrodes; hence obvious technical barriers exist in the interconnection and integration of MACs. Here we report a carbon nanotube (CNT)-clamped MAC, where CNTs play the roles of both nanoconnector and electrodes. This nanostructure is prepared by in situ machining a metal-filled CNT, including peeling off carbon shells by spatially and elementally selective electron beam irradiation and further elongating the exposed metal nanorod. The microstructure and formation process of this CNT-clamped MAC are explored by both transmission electron microscopy observations and theoretical simulations. First-principles calculations indicate that strong covalent bonds are formed between the CNT and MAC. The electrical transport property of the CNT-clamped MAC was experimentally measured, and quantized conductance was observed.
Hangovers of globalization
Authors: Siiner Maarja
Published: April 2010

Denmark is known for its rather “liberal” and implicit language policy. Many of the decisions concerning the use, acquisition and status of languages are influenced by political decisions made on other topics and by the changing governments’ hidden political agenda. Language policy is therefore not so much non-existent as it is hidden. The aim of the present article is to uncover the covert mechanisms of language policymaking and its relationship to the prevailing linguistic culture. The roots of the laissez-faire language policy in Denmark are planted deeply in the prevailing linguistic culture in the country, according to which sanctioning and controlling the use of language is conceived as discriminatory, as it is in conflict with the right to freedom of speech. However, recent sociolinguistic research carried out in Denmark bears witness to the fact that the laissez-faire or liberal language policy does not necessarily contribute to linguistic diversity, but quite to the contrary speeds up the opposite processes of standardization and dedialectalization.
How European is Esperanto?
Authors: Parkvall Mikael
Published: April 2010

The typological similarities between Esperanto and other languages have long been a matter of debate. Assuming that foreign-language structures are more easily acquired when they resemble those of the learner’s native tongue, any candidate for a global lingua franca obviously ought to be as typologically neutral as possible. One common criticism of Esperanto is that it is ‘too European,’ and thus less accessible to speakers of non-European languages. In order to provide a more solid base for such discussions, this paper makes an attempt to quantify the Eurocentricity of Esperanto, employing the features catalogued in the World Atlas of Language Structures. It is concluded that Esperanto is indeed somewhat European in character, but considerably less so than the European languages themselves.
Slippery pores: anti-adhesive effect of nanoporous substrates on the beetle attachment system
Authors: Gorb E. V. , Hosoda N. , Miksch C. , Gorb S. N.
Published: April 2010

Traction experiments with adult seven-spotted ladybird beetles
Coccinella septempunctata
(L.) were carried out to study the influence of surface structure on insect attachment. Force measurements were performed with tethered walking insects, both males and females, on five different substrates: (i) smooth glass plate, (ii) smooth solid Al
2
O
3
(sapphire) disc, and (iii–v) porous Al
2
O
3
discs (anodisc membranes) with the same pore diameter but different porosity. The traction force of beetles ranged from 0.16 to 16.59 mN in males and from 0.32 to 8.99 mN in females. In both sexes, the highest force values were obtained on smooth solid surfaces, where males showed higher forces than females. On all three porous substrates, forces were significantly reduced in both males and females, and the only difference within these surfaces was obtained between membranes with the highest and lowest porosity. Males produced essentially lower forces than females on porous samples. The reduction in insect attachment on anodisc membranes may be explained by (i) possible absorption of the secretion fluid from insect adhesive pads by porous media and/or (ii) the effect of surface roughness. Differences in attachment between males and females were probably caused by the sexual dimorphism in the terminal structure of adhesive setae.
Replication kinetics of neurovirulent versus non-neurovirulent equine herpesvirus type 1 strains in equine nasal mucosal explants
Authors: Vandekerckhove Annelies P. , Glorieux S. , Gryspeerdt A. C. , Steukers L. , Duchateau L. , Osterrieder N. , Van de Walle G. R. , Nauwynck H. J.
Published: April 2010

Equine herpesvirus type 1 (EHV-1) is the causative agent of equine herpes myeloencephalopathy, of which outbreaks are reported with increasing frequency throughout North America and Europe. This has resulted in its classification as a potentially emerging disease by the US Department of Agriculture. Recently, it was found that a single nucleotide polymorphism (SNP) in the viral DNA polymerase gene (ORF30) at aa 752 (N→D) is associated with the neurovirulent potential of EHV-1. In the present study, equine respiratory mucosal explants were inoculated with several Belgian isolates typed in their ORF30 as D752 or N752, to evaluate a possible difference in replication in the upper respiratory tract. In addition, to evaluate whether any observed differences could be attributed to the SNP associated with neurovirulence, the experiments were repeated with parental Ab4 (reference neurovirulent strain), parental NY03 (reference non-neurovirulent strain) and their N/D revertant recombinant viruses. The salient findings were that EHV-1 spreads plaquewise in the epithelium, but plaques never cross the basement membrane (BM). However, single EHV-1-infected cells could be observed below the BM at 36 h post-inoculation (p.i.) for all N752 isolates and at 24 h p.i. for all D752 isolates, and were identified as monocytic cells and T lymphocytes. Interestingly, the number of infected cells was two to five times higher for D752 isolates compared with N752 isolates at every time point analysed. Finally, this study showed that equine respiratory explants are a valuable and reproducible model to study EHV-1 neurovirulence in vitro, thereby reducing the need for horses as experimental animals.
Sequencing around 5-Hydroxyconiferyl Alcohol-Derived Units in Caffeic Acid O-Methyltransferase-Deficient Poplar Lignins
Authors: Lu Fachuang , Marita Jane M. , Lapierre Catherine , Jouanin Lise , Morreel Kris , Boerjan Wout , Ralph John
Published: April 2010

Caffeic acid O-methyltransferase (COMT) is a bifunctional enzyme that methylates the 5- and 3-hydroxyl positions on the aromatic ring of monolignol precursors, with a preference for 5-hydroxyconiferaldehyde, on the way to producing sinapyl alcohol. Lignins in COMT-deficient plants contain benzodioxane substructures due to the incorporation of 5-hydroxyconiferyl alcohol (5-OH-CA), as a monomer, into the lignin polymer. The derivatization followed by reductive cleavage method can be used to detect and determine benzodioxane structures because of their total survival under this degradation method. Moreover, partial sequencing information for 5-OH-CA incorporation into lignin can be derived from detection or isolation and structural analysis of the resulting benzodioxane products. Results from a modified derivatization followed by reductive cleavage analysis of COMT-deficient lignins provide evidence that 5-OH-CA cross couples (at its β-position) with syringyl and guaiacyl units (at their O-4-positions) in the growing lignin polymer and then either coniferyl or sinapyl alcohol, or another 5-hydroxyconiferyl monomer, adds to the resulting 5-hydroxyguaiacyl terminus, producing the benzodioxane. This new terminus may also become etherified by coupling with further monolignols, incorporating the 5-OH-CA integrally into the lignin structure.
The Molecular and Physiological Responses ofPhyscomitrella patensto Ultraviolet-B Radiation
Authors: Wolf Luise , Rizzini Luca , Stracke Ralf , Ulm Roman , Rensing Stefan A.
Published: April 2010

Ultraviolet-B (UV-B) radiation present in sunlight is an important trigger of photomorphogenic acclimation and stress responses in sessile land plants. Although numerous moss species grow in unshaded habitats, our understanding of their UV-B responses is very limited. The genome of the model moss Physcomitrella patens, which grows in sun-exposed open areas, encodes signaling and metabolic components that are implicated in the UV-B response in flowering plants. In this study, we describe the response of P. patens to UV-B radiation at the morphological and molecular levels. We find that P. patens is more capable of surviving UV-B stress than Arabidopsis (Arabidopsis thaliana) and describe the differential expression of approximately 400 moss genes in response to UV-B radiation. A comparative analysis of the UV-B response in P. patens and Arabidopsis reveals both distinct and conserved pathways.
Combination effect of a TGF‐β receptor kinase inhibitor with 5‐FU analog S1 on lymph node metastasis of scirrhous gastric cancer in mice
Authors: Shinto Osamu , Yashiro Masakazu , Kawajiri Hidemi , Shimizu Kiyoshi , Shimizu Toshiyuki , Miwa Atsushi , Hirakawa Kosei
Published: April 2010

Transforming growth factor‐β (TGF‐β) signals are closely associated with the distant metastases of gastric cancer. The aim of this study was to clarify the effect of a TGF‐β receptor I (TβR‐I) phosphorylation inhibitor, Ki26894, in combination with anticancer drugs, on the lymph node (LN) metastasis of scirrhous gastric cancer. A novel TβR‐I kinase inhibitor, Ki26894, inhibits the phosphorylation of Smad2 at the ATP binding site of TβR‐I. S1 is a 5‐fluorouracil analog. The human scirrhous gastric cancer cell line OCUM‐2MLN and the human gastric fibroblasts NF‐33 were used. OCUM‐2MLM cells in the upper well and NF‐33 cells in the lower well were co‐incubated with or without Ki26894. The proliferation of OCUM‐2MLN cells was significantly stimulated by co‐culture with NF‐33 cells. Ki26894 significantly suppressed the growth interactions between OCUM‐2MLN cells and NF‐33 cells. Gastric cancer models established by orthotopic inoculation of OCUM‐2MLN cells showed diffusely infiltrating gastric adenocarcinoma accompanied by LN metastases. We divided these mice into four groups, (control vehicle, Ki26894, S1, Ki26894 plus S1), and examined the effect of Ki26894 and/or S1 on phosphorylation of Smad2, tumor size, LN metastases, and lymphatic involvements. Ki26894 inhibited the Smad2 phosphorylation of cancer cells and decreased the extent of lymphatic involvement, compared with the control or S1 only group. The Ki26894 plus S1 administration group significantly suppressed tumor growth and decreased LN metastasis more effectively than either alone. These findings suggested that the TβR‐I kinase inhibitor with S1 is useful for the treatment of scirrhous gastric carcinoma with LN metastasis. (Cancer Sci 2010)
Induction of bone formation by transforming growth factor‐β2 in the non‐human primate Papio ursinus and its modulation by skeletal muscle responding stem cells
Authors: Ripamonti U. , Roden L. C.
Published: April 2010

Objectives:  Four adult non‐human primates Papio ursinus were used to study induction of bone formation by recombinant human transforming growth factor‐β2 (hTGF‐β2) together with muscle‐derived stem cells.

Materials and methods:  The hTGF‐β2 was implanted in rectus abdominis muscles and in calvarial defects with and without addition of morcellized fragments of striated muscle, harvested from the rectus abdominis or temporalis muscles. Expression of osteogenic markers including osteogenic protein‐1, bone morphogenetic protein‐3 and type IV collagen mRNAs from generated specimens was examined by Northern blot analysis.

Results:  Heterotopic intramuscular implantation of 5 and 25 μg hTGF‐β2 combined with 100 mg of insoluble collagenous bone matrix yielded large corticalized mineralized ossicles by day 30 with remodelling and induction of haematopoietic marrow by day 90. Addition of morcellized rectus abdominis muscle to calvarial implants enhanced induction of bone formation significantly by day 90.

Conclusions:  In Papio ursinus, in marked contrast to rodents and lagomorphs, hTGF‐β2 induced large corticalized and vascularized ossicles by day 30 after implantation into the rectus abdominis muscle. This striated muscle contains responding stem cells that enhance the bone induction cascade of hTGF‐β2. Induction of bone formation by hTGF‐β2 in the non‐human primate Papio ursinus may occur as a result of expression of bone morphogenetic proteins on heterotopic implantation of hTGF‐β2; the bone induction cascade initiated by mammalian TGF‐β proteins in Papio ursinus needs to be re‐evaluated for novel molecular therapeutics for induction of bone formation in clinical contexts.
Soluble factors from ASCs effectively direct control of chondrogenic fate
Authors: Kim B.‐S. , Kang K.‐S. , Kang S.‐K.
Published: April 2010

Background and objectives:  Adipose tissue‐derived stem cells (ASCs) have great potential for regenerative medicine. For molecular understanding of specific functional molecules present in ASCs, we analysed 756 proteins including specific chondrogenic functional factors, using high‐throughput nano reverse‐phase liquid chromatography–electrospray ionization–tandem mass spectrometry.

Materials, methods and results:  Of these proteins, 33 were identified as chondrogenic factors or proteins including type 2 collagen, biglycan, insulin‐like growth factor‐binding protein and transforming growth factor‐beta 1 (TGF‐β1). ASCs are a possible cell source for cartilage regeneration as they are able to secrete a number of functional cytokines including chondrogenesis‐inducing molecules such as TGF‐β1 and bone morphogenetic protein 4 (BMP4). The chondrogenic phenotype of cultured ASCs was effectively induced by ASC‐culture media (CM) containing BMP4 and TGF‐β1, and maintained after pre‐treatment for 14 days in vitro and subcutaneous implantation in vivo. Chondrogenic differentiation efficiency of cultured ASCs and cultured mouse skin‐derived progenitor cells (SPCs) depended absolutely on ASC CM‐fold concentration. Cell density was also a very important factor for chondrogenic behaviour development during differentiation of ASCs and SPCs.

Conclusion:  ASC CM‐derived TGF‐β1‐induced chondrogenic differentiation of ASCs resulted in significant reduction in chondrogenic activity after inhibition of the p38 pathway, revealing involvement of this MAPK pathway in TGF‐β1 signalling. On the other hand, TGF‐β1 signalling also led to SMAD activation that could directly increase chondrogenic activity of ASCs.
Carbamylated erythropoietin increases frataxin independent from the erythropoietin receptor
Authors: Sturm Brigitte , Helminger Melissa , Steinkellner Hannes , Heidari Mohammad Mehdi , Goldenberg Hans , Scheiber‐Mojdehkar Barbara
Published: April 2010

Eur J Clin Invest 2010; 40 (6): 561–565

Background  Friedreich’s ataxia (FRDA) is a neurodegenerative disorder caused by decreased expression of the mitochondrial protein frataxin. Recently we showed in a clinical pilot study in Friedreich’s ataxia patients that recombinant human erythropoietin (rhuEPO) significantly increases frataxin‐expression. In this in vitro study, we investigated the role of the erythropoietin receptor (EPO‐R) in the frataxin increasing effect of rhuEPO and if nonerythropoietic carbamylated erythropoietin (CEPO), which cannot bind to the classical EPO‐R increases frataxin expression.

Materials and methods  In our experiments human erythroleukaemic K562 cells (+ EPO‐R), human monocytic leukemia THP‐1 cells (− EPO‐R) and isolated primary lymphocytes from healthy control and FRDA patients were incubated with different concentrations of rhuEPO or CEPO. Frataxin‐expression was detected by an electrochemical luminescence immunoassay (based on the principle of an ELISA).

Results  We show that rhuEPO increases frataxin‐expression in K562 cells (expressing EPO‐R) as well as in THP‐1 cells (without EPO‐R expression). These results were confirmed by the finding that CEPO, which cannot bind to the classical EPO‐R increased frataxin expression in the same concentration range as rhuEPO. In addition, we show that both EPO derivatives significantly increase frataxin‐expression in vitro in control and Friedreich’s ataxia patients primary lymphocytes.

Conclusion  Our results provide a scientific basis for further studies examining the effectiveness of nonerythropoietic derivatives of erythropoietin for the treatment of Friedreich’s ataxia patients.
Temperature sensitivity of suicidal erythrocyte death
Authors: Föller Michael , Braun Manuel , Qadri Syed M. , Lang Elisabeth , Mahmud Hasan , Lang Florian
Published: April 2010

Eur J Clin Invest 2010; 40 (6): 534–540

Background  Fever and hyperthermia are frequently associated with anaemia. Under most clinical conditions, they are considered to be two mutually independent clinical consequences of a common cause. The present study explored the possibility that anaemia results from temperature‐sensitive suicidal erythrocyte death or eryptosis. Eryptosis is characterised by cell shrinkage and cell membrane scrambling with phosphatidylserine (PS) exposure at the erythrocyte surface. It is triggered by increase in the cytosolic Ca2+ activity on the one hand and by ceramide formation on the other.

Material and methods  Annexin V‐binding was utilised to disclose PS exposure, forward scatter to analyse cell volume, Fluo 3 fluorescence to estimate cytosolic Ca2+ activity, binding of fluorescent antibodies to determine ceramide abundance and a luciferin/luciferase‐based assay to measure the cytosolic ATP concentration.

Results  Graded increases in temperature from 37 to 41 °C decreased the forward scatter and stimulated annexin V‐binding of human erythrocytes. The effect was accompanied by increased cytosolic Ca2+ activity, decrease of the cellular ATP content and a moderate rise in ceramide formation. The effect of hyperthermia on annexin V‐binding was significantly blunted by the leukotriene receptor CysLT1 antagonist cinalukast (1 μM).

Conclusions  Hyperthermia stimulates Ca2+ entry into erythrocytes leading to cell shrinkage and PS exposure. As PS‐exposing erythrocytes are rapidly cleared from circulating blood, the eryptosis during hyperthermia may cause anaemia.
Mitochondrial genetic diversity and gene flow of common carp from main river drainages in China
Authors: WANG CHENGHUI , LIU HAO , LIU ZHIZHI , WANG JUN , ZOU JIXIN , LI XUEJUN
Published: April 2010

1. The common carp (Cyprinus carpioL.) is one of the most widely distributed and important freshwater fishes in the world. In China, the common carp has been recognised as three subspecies:C. carpio haematopterus,C. carpio rubrofuscusandC. carpio carpio.The Nanling Mountains have been suggested as providing the dividing line betweenC. carpio haematopterusandC. carpio rubrofuscus. However, the demographic history and gene flow of the common carp in China is not clear.

2. We collected mitochondrial COII and D‐loop sequences (1494 bp) from 241 individuals distributed in eight major river drainages across China. The objective was to provide the first investigation into population genetic structure, demographic history and migration patterns of the common carp from these river drainages, and to assess the validity of the three subspecies.

3. Phylogenetic analysis did not result in three major monophyletic lineages corresponding to the three subspecies. The Nanling Mountains do not form a border separatingC. carpio haematopterusandC. carpio rubrofuscus.amovashowed low population differentiation, with 11.60% of the molecular variance found among river drainages. PairwiseFSTvalues between river drainages were moderate (0.0331–0.2617). Substantial gene flow detected in coalescent analysis between drainages showed that the Yangtze drainage was the centre from which migrants moved northward, southward and north‐westward. Human‐mediated translocation has confounded our ability to identify subspecies of common carp in China.
Effect of increasing plant maturity in timothy‐dominated grass silage on the performance of growing/finishing Norwegian Red bulls
Authors: Randby Å. T. , Nørgaard P. , Weisbjerg M. R.
Published: April 2010

An investigation was made of the potential for attaining high daily live weight (LW) gain, high feeding efficiency and carcass quality in Norwegian Red (NRF) bulls fed grass silage harvested at early stages of maturity, supplemented with minimal amounts of concentrates. Roundbale silage was produced from timothy‐dominated swards harvested at three stages of maturity: stages 1 and 2 were dominated by tillers in stem elongation with two and three visible nodes, respectively, and stage 3 by tillers at early heading, with visible heads, but without head stems. Crops were wilted rapidly and a formic acid‐based additive applied. All silages were preserved with restricted fermentation. Silage DOMD values were 0·747, 0·708 and 0·647 for harvesting time (H) 1, 2 and 3 respectively. Silages were fed ad libitum as sole feed, or supplemented with 2–4 kg concentrate at increasing LW, to six bulls per treatment from age 7 months (288 kg) to slaughter at 575 kg. Daily LW gain for bulls fed unsupplemented silage was 1423, 1262 and 936 g, respectively, for H1, H2 and H3, and 1570, 1567 and 1357 g for supplemented bulls. For concentrate‐supplemented bulls, higher energy intake increased proportions of carcass fat more for H1 (0·163) than for H2 (0·134) but the same amount of energy was retained in the carcass per MJ net energy growth intake for these two groups. It is concluded that, apart from milk and concentrate fed to calves during the first months, an intensive beef production with NRF bulls finished before 15 months of age may be based entirely on local grass resources.
Expression of classical NF‐κB pathway effectors in human ovarian carcinoma
Authors: Darb‐Esfahani Silvia , Sinn Bruno V , Weichert Wilko , Budczies Jan , Lehmann Annika , Noske Aurelia , Buckendahl Ann‐Christin , Müller Berit Maria , Sehouli Jalid , Koensgen Dominique , Györffy Balazs , Dietel Manfred , Denkert Carsten
Published: April 2010

Darb‐Esfahani S, Sinn B V, Weichert W, Budczies J, Lehmann A, Noske A, Buckendahl A‐C, Müller B M, Sehouli J, Koensgen D, Györffy B, Dietel M & Denkert C (2010) Histopathology 56. 727–739 Expression of classical NF‐κB pathway effectors in human ovarian carcinoma

Aims:  Functional studies have demonstrated that nuclear factor (NF)‐κB promotes tumour progression in ovarian cancer cells. However, surprisingly little is known of the expression of effectors of the NF‐κB pathway in human ovarian cancer in vivo.

Methods and results:  Immunohistochemistry and in situ hybridization revealed that in a cohort of 85 primary ovarian carcinomas, total p65 expression was inversely correlated to nuclear and cytoplasmic phospho‐IκBα (P = 0.002 and P = 0.05, respectively), and IκBα mRNA expression (P = 0.032). In contrast, phospho‐p65 expression was paralleled by the expression of nuclear (P = 0.027) and cytoplasmic phospho‐IκBα (P = 0.01). Total p65 expression was an adverse prognostic factor for overall survival (P = 0.018). In contrast, total IκBα and phosphorylated nuclear and cytoplasmic IκBα expression were favourable prognostic markers (P = 0.001, P = 0.031, P = 0.001, respectively). Cytoplasmic phospho‐IκBα expression remained a significant prognostic factor on multivariate analysis (P = 0.010). In cultured, stimulated OVCAR‐3 ovarian cancer cells the cytoplasmic retranslocation of p65 was delayed by inhibition of the nuclear membrane transporter chromosomal region maintenance/exportin1 protein (CRM1). A positive association of p65 and CRM1 expression was demonstrated in ovarian cancer tissue (P < 0.0001).

Conclusions:  Total and phosphorylated IκBα protein expression might serve as markers for NF‐κB activation in human ovarian carcinoma. Cytoplasmic localization of p65 may be related to deregulated nucleocytoplasmic transport in carcinomas overexpressing CRM1.
Reproducibility in the diagnosis of needle core biopsies of non‐palpable breast lesions: an international study using virtual slides published on the world‐wide web
Authors: Zito Francesco Alfredo , Verderio Paolo , Simone Giovanni , Angione Vito , Apicella Paola , Bianchi Simonetta , Conde Antonio Felix , Hameed Omar , Ibarra Julio , Leong Antony , Pennelli Natale , Pezzica Ezio , Vezzosi Vania , Ventrella Vincenzo , Pizzamiglio Sara , Paradiso Angelo , Ellis Ian
Published: April 2010

Zito F A, Verderio P, Simone G, Angione V, Apicella P, Bianchi S, Conde A F, Hameed O, Ibarra J, Leong A, Pennelli N, Pezzica E, Vezzosi V, Ventrella V, Pizzamiglio S, Paradiso A & Ellis I (2010) Histopathology 56, 720–726 Reproducibility in the diagnosis of needle core biopsies of non‐palpable breast lesions: an international study using virtual slides published on the world‐wide web

Aims:  To conduct an internet‐based study using virtual slides (VS) of sterotactic core biopsy specimens of non‐palpable breast lesions in order to evaluate interobserver reproducibility between pathologists.

Methods and results:  A total of 18 breast lesions, determined to be histologically complex by two pathologists, were selected. Digitized VSs were then created using QuickTime Virtual Reality technology (Apple, Cupertino, CA, USA) and posted on the world‐wide web. In all, 10 pathologists completed the evaluations of 18 VSs using the five diagnostic categories (B1–B5) from the European guidelines for quality assurance in breast cancer screening and diagnosis. Their results were compared with those of every other participating pathologist, and were then individually compared with the results of a highly experienced breast pathologist (referee). Of the 18 cases, 10 (56%) were classified by the referee as borderline (B3 and B4). Comparisons with reference values showed a less than satisfactory level of reproducibility (median κw = 0.60). As regards interobserver reproducibility, results showed that, in general, the level of agreement was not satisfactory (median κw = 0.53).

Conclusions:  Overall, the findings are comparable to those quality control studies using circulating slides when analysis is done on borderline cases.
Cumulative alterations of p27Kip1‐related cell‐cycle regulators in the development of endometriosis‐associated ovarian clear cell adenocarcinoma
Authors: Yamamoto Sohei , Tsuda Hitoshi , Miyai Kosuke , Takano Masashi , Tamai Seiichi , Matsubara Osamu
Published: April 2010

Yamamoto S, Tsuda H, Miyai K, Takano M, Tamai S & Matsubara O (2010) Histopathology 56, 740–749 Cumulative alterations of p27Kip1‐related cell‐cycle regulators in the development of endometriosis‐associated ovarian clear cell adenocarcinoma

Aims:  To identify the key cell‐cycle dysregulations in the development of endometriosis‐associated ovarian clear cell adenocarcinoma (CCA).

Methods and results:  Expression of p27Kip1‐interacting cell‐cycle regulators, such as p27Kip1 itself, Skp2, cyclin‐dependent kinase subunit 1 (Cks1), cyclin A and cyclin E, and Ki67 labelling index (LI), were analysed by immunohistochemistry in 23 CCAs with 36 endometriotic or atypical endometriotic lesions adjacent to CCA from a cohort of 23 patients, and in 31 cases of solitary endometriosis. The cell‐cycle regulators examined were overexpressed (Skp2, Cks1, cyclin A and cyclin E; P < 0.01, each) or down‐regulated (p27Kip1, P = 0.044) significantly more frequently in the CCAs than in the adjacent endometriosis. The frequency of Skp2 overexpression was significantly higher in atypical endometriosis than in endometriosis, and the frequency of Skp2 and cyclin A overexpression was significantly higher in CCA than in atypical endometriosis (P < 0.01, each). Mean Ki67 LI increased from endometriosis (8.4%) through atypical endometriosis (21.4%) to CCA (46.9%), with statistical significance between each component (P < 0.01, each). The frequency of cell‐cycle regulator expression and mean Ki67 LIs were not significantly different between solitary endometriosis and endometriosis adjacent to CCA.

Conclusions:  Alteration of the p27Kip1‐interacting cell‐cycle regulators appeared strongly involved in the progression of endometriosis‐associated ovarian clear cell carcinogenesis through increasing cell proliferative activity.
Glypican 3 has a higher sensitivity than alpha‐fetoprotein for testicular and ovarian yolk sac tumour: immunohistochemical investigation with analysis of histological growth patterns
Authors: Zynger Debra L , McCallum John C , Luan Chunyan , Chou Pauline M , Yang Ximing J
Published: April 2010

Zynger D L, McCallum J C, Luan C, Chou P M & Yang X J (2010) Histopathology 56, 750–757 Glypican 3 has a higher sensitivity than alpha‐fetoprotein for testicular and ovarian yolk sac tumour: immunohistochemical investigation with analysis of histological growth patterns

Aims:  Glypican 3 (GPC3) has been reported to be overexpressed in yolk sac tumour (YST), but the sensitivity has not been compared with α‐fetoprotein (AFP). YST can form numerous growth patterns and the expression of GPC3 in these patterns has not been studied. The aim was to address these aspects.

Methods and results:  Sections from testicular or ovarian YST were subjected to immunohistochemistry using GPC3 (n = 39) and AFP (n = 24). Overall immunoreactivity for each case and specific histological patterns were semiquantitatively evaluated (0–3+) and intensity of reactivity was scored (0–3). All cases expressed GPC3 (1+, 5%; 2+, 8%; 3+, 87%) with strong intensity (2.9). The majority expressed AFP (58%) but immunoreactivity was often focal (0, 42%; 1+, 33%; 2+, 25%) and intensity was low (1.0). Using GPC3, >75% of the microcystic (n = 38), macrocystic (n = 26), solid (n = 21), glandular‐alveolar (n = 8), endodermal sinus (n = 7), polyvesicular vitelline (n = 5), enteric (n = 4) and micropapillary (n = 2) growth patterns displayed 2+ or 3+ positivity.

Conclusions:  YST can display a variety of growth patterns that can be confused with other germ cell tumour components. GPC3 detects all growth patterns tested and has a higher sensitivity for detecting YST than AFP.
Breeding tef [Eragrostis tef (Zucc.) trotter]: conventional and molecular approaches
Authors: Assefa K. , Yu J.‐K. , Zeid M. , Belay G. , Tefera H. , Sorrells M. E.
Published: April 2010

With 2 figures and 5 tables

Tef [Eragrostis tef (Zucc.) Trotter] is an important food staple cereal crop in Ethiopia. Despite its importance in the Ethiopian agriculture, there are constraints that need to be addressed through scientific research. The major constraints are low yield of landrace cultivars under widespread cultivation, susceptibility to lodging and a lack of knowledge concerning the genetic control of agronomic traits. Conventional tef breeding efforts started in the late 1950s, and since then a total of 24 varieties have been developed and released. Yield gain from tef breeding has been linear with an average annual increase of 0.8%. Tef genomics has provided much molecular genetic information on important agronomic traits. More than 1500 PCR‐based molecular markers have been developed and several genetic linkage maps based on intra‐ and inter‐specific crosses have been constructed. Results from quantitative trait loci studies have provided information necessary for marker‐assisted selection. Lodging is the number one cause of yield loss in tef. Recently, molecular breeding techniques and biotechnologies are being employed to understand the genetic control of lodging.
Long‐term follow up of autologous serum treatment for recurrent corneal erosions
Authors: Ziakas Nikolaos G , Boboridis Konstantinos G , Terzidou Chryssa , Naoumidi Tatiana L , Mikropoulos Dimitris , Georgiadou Eirini N , Georgiadis Nick S
Published: April 2010

Abstract

Purpose:  The aim of the study was to evaluate long‐term results of autologous serum treatment for recurrent corneal erosions.

Methods:  In this prospective single‐centre study, 33 eyes of 33 patients (21 male and 12 female) were treated with autologous serum eye drops for recurrent corneal erosions. Mean age of the patients was 49.3 ± 9.8 standard deviation (range 24–73) years. All subjects had failed to respond to other treatments. Autologous serum drops were administered for a 6‐month period: six times daily for the first 3 months and four times daily for the remaining 3 months. Detailed informed consent was obtained from the entire patient group before the study.

Results:  The mean follow‐up period was 30 ± 6.3 standard deviation (range 12–48) months. None of the patients experienced a recurrence while under treatment. Twenty‐eight patients (85%) had complete healing of erosions with no relapses of the disease over the whole follow‐up period. Five patients (15%) presented a single recurrence 3–12 months after the end of the treatment. No sight‐threatening complications were reported over the follow up. There was no statistically significant difference in the best spectacle‐corrected visual acuity values (tstat = 2.1, F = 0.096, degree of freedom = 40 166, P < 0.41) or in the intraocular pressure measurements (P < 0.38) between the pre‐ and post‐treatment patient groups.

Conclusions:  Autologous serum drops proved to be a safe and efficient treatment modality for patients with recurrent corneal erosion syndrome as observed through a long‐term follow up.
Comparative study of three prostaglandin analogues in the treatment of newly diagnosed cases of ocular hypertension, open‐angle and normal tension glaucoma
Authors: Faridi Usama A , Saleh Tarek A , Ewings Paul , Venkateswaran Meenakshi , Cadman David H , Samarasinghe Rohana A , Vodden Julie , Claridge Kate G
Published: April 2010

Abstract

Background:  To compare the efficacy and tolerance of three prostaglandin analogues, bimatoprost, latanoprost and travoprost in patients with previously untreated open‐angle glaucoma and ocular hypertension.

Methods:  Prospective randomized single (investigator) masked comparative clinical trial at the Taunton and Somerset NHS Hospital, Taunton, UK. Newly diagnosed, treatment naïve glaucoma/ocular hypertension patients were recruited. Patients were randomized into three groups to receive one of the three prostaglandin analogues. Intraocular pressure (IOP) was measured before starting treatment and after 2 and 6 months of treatment. The IOP reduction and the tolerance profile of each drug were compared. The data were analysed on the basis of intention to treat, using analysis of covariance comparing IOP in the three groups at 2 and 6 months, adjusting for baseline IOP. Tolerance levels were compared using Kruskal–Wallis test.

Results:  Of the 122 patients, 40 patients were given bimatoprost, 42 received latanoprost and 40 had travoprost. At 2 months, there was a significant difference between the three treatment groups (P = 0.013) with bimatoprost achieving a greater reduction in IOP than the other two drops. However, at 6 months, the difference was not statistically significant (P = 0.13). There was no significant difference in the tolerance profile.

Conclusion:  All the three topical prostaglandin analogues are effective at lowering IOP, but bimatoprost was found to be most effective in the initial phase of the trial, and there was no statistically significant difference in the efficacy, among the three prostaglandin analogue eye drops after 6 months of treatment.
Native plantations as an important element for biodiversity in vanishing forested landscapes: A study of the near threatened araucaria tit spinetail (Leptasthenura setaria, Furnariidae)
Authors: PIETREK ALEJANDRO G. , BRANCH LYN C.
Published: April 2010

Although forest loss is still a problem worldwide, estimated rates of deforestation have declined in the last decade, primarily because of an increase in the area of tree plantations. This leads to the central question of how suitable plantations are for indigenous species. Native plantations are thought to have higher value for biodiversity than plantations of non‐native trees; however, not all studies support this view. We assessed occupancy and density of the araucaria tit spinetail (Leptasthenura setaria, Furnariidae), a near threatened species, in the highly endangered araucaria forests of north‐eastern Argentina and in araucaria plantations, which comprise 90% of the remaining habitat for this species. All natural forest remnants were occupied by araucaria tit spinetails. Only 85% of the plantations were occupied; however, density was almost threefold higher in plantations compared with natural forests. Our models indicated that stand age was the most important factor in determining occupancy and density of this bird species in plantations. Plantations <10 years old exhibited lower densities than older plantations. This species does not occur in plantations of non‐native trees, but our results indicate that native plantations may provide important habitat for the araucaria tit spinetail, particularly given that most native forest has been removed. Restoration of natural remnants and conservation of old, connected plantations may assure the protection of significant populations of spinetails. The role of native araucaria plantations as habitat for other species merits further examination.
Balancing Internal and External Knowledge Acquisition: The Gains and Pains from R&D Outsourcing
Authors: Grimpe Christoph , Kaiser Ulrich
Published: April 2010

abstract

The outsourcing of research and development (R&D) activities has frequently been characterized as an important instrument to acquire external technological knowledge that is subsequently integrated into a firm's own knowledge base. However, in this paper we argue that these ‘gains’ from R&D outsourcing need to be balanced against the ‘pains’ that stem from a dilution of firm‐specific resources, the deterioration of integrative capabilities and the high demands on management attention. Based on a panel dataset of innovating firms in Germany, we find evidence for an inverse U‐shaped relationship between R&D outsourcing and innovation performance. This relationship is positively moderated by the extent to which firms engage in internal R&D and by the breadth of formal R&D collaborations: both serve as an instrument to increase the effectiveness of R&D outsourcing.
Farms and families in ninth‐century Provence
Authors: Faith Rosamond
Published: April 2010

Information about the people recorded in 813–14 on the estate of St Victor de Marseilles shows that although considered to belong to the monastery they were an independent peasant class. Family size and structure varied: some farms were run by the labour of the family which included unmarried sons and ‘married‐in’ sons‐in‐law; other farmers employed living‐in servants in husbandry. The mountain sheep farms had large groups of unmarried young people. Inheritance systems ensured that the peasant family property remained intact over the generations and provided support for unmarried sons who remained to work there.
The importance of quality of care: effects of perinatal HIV infection and early institutional rearing on preschoolers’ attachment and indiscriminate friendliness
Authors: Dobrova‐Krol Natasha A. , Bakermans‐Kranenburg Marian J. , van IJzendoorn Marinus H. , Juffer Femmie
Published: April 2010

Background:  The rearing environment of human immunodeficiency virus (HIV)‐infected children is often compromised, putting these children at additional risks. Positive caregiving may ameliorate the impact of adverse circumstances and promote attachment security. The goal of the present study was to examine the attachment relationships of HIV‐infected children in biological families and institutions; to examine the effects of HIV infection and institutional rearing on attachment security and indiscriminate friendliness; and to assess the role of caregiving in the face of HIV‐related adversities.

Methods:  We studied 64 Ukrainian uninfected and HIV‐infected children reared in families and institutions (mean age 50.9 months). Physical and cognitive development of children as well as attachment‐related domains and indiscriminate friendliness were assessed.

Results:  Institutional care but not the presence of HIV was associated with lower levels of attachment security and higher levels of indiscriminate friendliness. On average, the level of indiscriminate friendliness among institution‐reared children was more than twice as high as among family‐reared children. Only 24% of institution‐reared children had clearly developed attachment patterns, as opposed to 97% among family‐reared children. Controlling for physical and cognitive development, type of care (institution or family), and HIV status, positive caregiving was associated with higher levels of attachment security. Indiscriminate friendliness was associated with lower levels of attachment security among family‐reared children, but with higher levels of positive caregiving among institution‐reared children.

Conclusions:  Etiology and function of indiscriminate friendliness may differ for family‐reared versus institution‐reared children. The findings of this study suggest the necessity of early interventions improving the quality of care for HIV‐infected children.
Improving the flavor of fresh fruits: genomics, biochemistry, and biotechnology
Authors: Klee Harry J.
Published: April 2010

It is generally accepted that the flavor quality of many fruits has significantly declined over recent decades. While some of this decline can be linked to selection for certain traits, such as firmness and postharvest shelf life, that run counter to good flavor, a major contributing factor has been the challenge of breeding for such a complex quality trait. Flavor involves integration of sugars, acids and a set of 20 or more volatile chemicals. Together, these compounds involve a large number of primary and secondary metabolic pathways, many of which have only recently been established. This review describes recent advances in the understanding of the pathways and genes controlling synthesis of the volatile components of flavor. Because of tomato’s unique role as a model for fruit development, the review emphasizes advances in this fruit. In the last decade we have literally advanced from a list of chemicals known to influence flavor to a detailed understanding of how and where they are made. However, our knowledge of the regulation of the critical metabolic pathways is still limited. Nonetheless, the pieces are in place for rapid advances to be made in the manipulation of flavor chemistry in the immediate future.

Contents

Summary
44

I.
Introduction
44

II.
The importance of flavor and nutrition
45

III.
Defining the problem
45

IV.
Where did the flavor go?
48

V.
Identifying the important genes
48

VI.
Biosynthetic gene isolation
49

VII.
Fixes
53

VIII.
Conclusions
54

References
54
Randomised prospective single‐blinded study comparing ‘inside‐out’ versus ‘outside‐in’ transobturator tapes in the management of urodynamic stress incontinence: 1‐year outcomes from the E‐TOT study
Authors: Abdel‐fattah M , Ramsay I , Pringle S , Hardwick C , Ali H , Young D , Mostafa A
Published: April 2010

Please cite this paper as: Abdel‐fattah M, Ramsay I, Pringle S, Hardwick C, Ali H, Young D, Mostafa A. Randomised prospective single‐blinded study comparing ‘inside‐out’ versus ‘outside‐in’ transobturator tapes in the management of urodynamic stress incontinence: 1‐year outcomes from the E‐TOT study. BJOG 2010;117:870–878.

Objective  To compare the ‘inside‐out’ versus ‘outside‐in’ routes for transobturator tape insertion for urodynamic stress incontinence, and to identify independent risk factors for failure at 1 year.

Design  Prospective single‐blinded randomised trial.

Setting  Tertiary urogynaecology centre.

Population  A cohort of 341 women undergoing transobturator tape procedures between April 2005 and April 2007.

Methods  Women were randomised to tension‐free vaginal tape‐obturator (TVT)‐O™ for the ‘inside‐out’ route (n = 170) and transobturator tape (TOT)‐ARIS® for the ‘outside‐in’ route (n = 171). Participants completed validated symptom‐severity, quality‐of‐life and sexual‐function questionnaires before and after surgery. In addition, they completed the patient global impression of improvement questionnaire (PGI‐I) and standard 1‐hour pad test postoperatively.

Main outcome measures  The primary outcome was the patient‐reported success rate reported on the PGI‐I scale. Secondary outcomes included objective cure rate and improvement in King’s Health Questionnaire scores.

Results  A total of 341 women were recruited: 171 women to the ‘outside‐in’ (TOT‐ARIS®) group and 170 to the ‘inside‐out’ (TVT‐O™) group; 299 completed the 1‐year follow up. The patient‐reported success rate was 80% with no statistically significant differences between the groups (‘outside‐in’ 77.6% versus ‘inside‐out’ 81.2%; OR 1.25; 95% CI 0.71, 2.20; P = 0.54). The objective cure rate was 91% with no statistically significant difference between the groups (‘outside‐in’ 88% versus ‘inside‐out’ 94%; OR 2.21; 95% CI 0.85, 5.75; P = 0.157). Previous incontinence surgery (OR 1.41; 95% CI 1.18, 1.91; P = 0.029) and preoperative urgency incontinence (OR 1.78; 95% CI 1.21, 3.91, P = 0.048) were significant risk factors for failure of transobturator tape at the 1‐year follow up.

Conclusions  There are no significant differences in patient reported and objective cure rates between ‘inside‐out’ and ‘outside‐in’ transobturator tapes. Quality of life and sexual function significantly improved following surgery. Both previous incontinence surgery and preoperative urgency incontinence are associated with significantly lower patient‐reported cure rates.
Progestogen treatment options for early endometrial cancer
Authors: Cade TJ , Quinn MA , Rome RM , Neesham D
Published: April 2010

Please cite this paper as: Cade T, Quinn M, Rome R, Neesham D. Progestogen treatment options for early endometrial cancer. BJOG 2010;117:879–884.

Objective  Premenopausal women with early endometrial cancer may wish to maintain their fertility, and for some patients non‐surgical treatment options may be attractive. We have examined our own experience with such patients, as there are limited published data so far to support clear guidelines in this area.

Design  Retrospective analysis of a case series.

Setting  Case series from a specialist gynaecological oncology unit in a major tertiary referral hospital.

Sample  Sixteen patients receiving progestogen therapy for stage‐1 endometrial cancer.

Methods  We reviewed our experience of all patients receiving progestogen therapy for stage‐1 endometrial cancer, and we particularly examined their cancer‐free outcome and fertility potential.

Main outcome measures  Response to treatment, duration of response, and subsequent pregnancies.

Results  Of the 16 patients investigated, four received an oral progestogen, five received the levonorgestrel‐releasing intrauterine system (Mirena), and seven received both forms of treatment. Ten patients (63%) responded to treatment, with a median time to response of 5.5 months. Six patients did not respond to treatment, but all were either early in treatment or opted for surgical management before the average time of response. No patient who responded had a later recurrence. The mean total follow‐up time was 27 months (range 3–134 months), with no patient deaths. Three patients had successful pregnancies, with one patient having two children.

Conclusions  This form of treatment appears to be a realistic treatment option in selected patients in the closely supervised environment of a specialist gynaecological oncology unit.