bluuebunny/crossref_metadata_2025 huggingface dataset:
Taming the plasma–material interface with the ‘snowflake’ divertor in NSTX
Authors: Soukhanovskii V.A. , Ahn J.-W. , Bell R.E. , Gates D.A. , Gerhardt S. , Kaita R. , Kolemen E. , LeBlanc B.P. , Maingi R. , Makowski M. , Maqueda R. , McLean A.G. , Menard J.E. , Mueller D. , Paul S.F. , Raman R. , Roquemore A.L. , Ryutov D.D. , Sabbagh S.A. , Scott H.A.
Published: December 2010

Steady-state handling of divertor heat flux is a critical issue for ITER and future conventional and spherical tokamaks with compact high-power density divertors. A novel ‘snowflake’ divertor (SFD) configuration was theoretically predicted to have significant magnetic geometry benefits for divertor heat flux mitigation, such as an increased plasma-wetted area and a higher divertor volume available for volumetric power and momentum loss processes, as compared with the standard divertor. Both a significant divertor peak heat flux reduction and impurity screening have been achieved simultaneously with core H-mode confinement in discharges with the SFD using only a minimal set of poloidal field coils.
Direct renin inhibition in addition to or as an alternative to angiotensin converting enzyme inhibition in patients with chronic systolic heart failure: rationale and design of the Aliskiren Trial to Minimize OutcomeS in Patients with HEart failuRE (ATMOSPHERE) study
Authors: Krum Henry , Massie Barry , Abraham William T. , Dickstein Kenneth , Kober Lars , McMurray John J.V. , Desai Ashkay , Gimpelewicz Claudio , Kandra Albert , Reimund Bernard , Rattunde Henning , Armbrecht Juergen ,   on behalf of the ATMOSPHERE Investigators
Published: December 2010

Aims

The renin–angiotensin–aldosterone system (RAAS) represents a key therapeutic target in heart failure (HF) management. However, conventional agents that block this system induce a reflex increase in plasma renin activity (PRA), which may lead to RAAS ‘escape'. Direct renin inhibitors (DRIs) have been developed that decrease PRA and thus may provide a greater RAAS blockade. Aliskiren is the first orally active DRI. Plasma levels of B‐type natriuretic peptide (BNP) have been observed to be reduced with aliskiren compared with placebo. The aim of the Aliskiren Trial of Minimizing OutcomeS for Patients with HEart failuRE (ATMOSPHERE) study is to evaluate the effect of both aliskiren and enalapril monotherapy and aliskiren/enalapril combination therapy on cardiovascular death and HF hospitalization in patients with chronic systolic HF, NYHA functional class II–IV symptoms, and elevated plasma levels of BNP.

Methods

Patients tolerant to at least 10 mg or equivalent of enalapril will undergo an open‐label run‐in period where they receive enalapril then aliskiren. Approximately 7000 patients tolerating this run‐in period will then be randomized 1:1:1 to aliskiren monotherapy, enalapril monotherapy, or the combination. The primary endpoints of ATMOSPHERE are (i) whether the aliskiren/enalapril combination is superior to enalapril monotherapy in delaying time to first occurrence of cardiovascular death or HF hospitalization and (ii) whether aliskiren monotherapy is superior or at least non‐inferior to enalapril monotherapy on this endpoint.

Perspective

The ATMOSPHERE study will definitively determine the role of a DRI strategy additional to or as an alternative to conventional RAAS blockade in patients with chronic systolic HF.
GAY SCIENCE AND (NO) LAUGHING MATTER: THE ETERNAL RETURNS OF MICHEL HOUELLEBECQ
Authors: Moore Gerald
Published: December 2010

Michel Houellebecq has repeatedly presented his literary work as something of a return to Schopenhauer. Yet this interpretation risks understating the complexity of Houellebecq's negotiations with Nietzsche — the self-proclaimed enemy of Schopenhauer — and the Nietzscheanism of
la génération 68
. In particular, it overlooks both his repetition of the Nietzschean themes of eternal return and Zarathustran laughter and the constitutive parody of this repetition, the effect of which is simultaneously to offer, withdraw, and suspend the withdrawal of the criticisms he articulates. The ambiguity plays out across
Les Particules élémentaires
(1998) and
La Possibilité d'une île
(2005), both of which can be read as staging a tension between two extreme, commodified versions of eternal return, namely the exhausted pseudo-transgression of popularized Zarathustra and a literal eternal return achieved through the science of cloning. These parodies of science and laughter contribute to Houellebecq's depiction of lifelessness rather than the joys of existence, but manage to preserve the prospect of affirming life in spite of nihilism. Filtered through an imminent critique of the post-68 reduction of philosophy to laughter, parody becomes a condition of Houellebecq's earnest reworking of the French Nietzschean legacy.
Time to positivity of neonatal blood cultures: fast and furious?
Authors: Guerti Khadija , Devos Helena , Ieven Margareta M. , Mahieu Ludo M.
Published: December 2010

The aim of this study was to determine the time to positivity (TTP) of neonatal blood cultures, to investigate differences between early onset versus late-onset sepsis, and non-proven versus proven sepsis, and to examine differences in TTP by organism type using a retrospective observational study at the Neonatal Intensive Care Unit, Antwerp University Hospital, Belgium. The subjects were 1828 neonates with suspected sepsis who were treated with antimicrobials for at least 3 days. The TTP was recorded for all episodes of suspected sepsis in an approximately 6.5 year period. A total of 2916 blood cultures were collected, of which 437 (15 %) became positive. The overall TTP was 21.33 h (Q1–Q313.17–32.46). The difference between the median TTP in early onset versus late-onset sepsis was 0.83 h (22.00 versus 21.17 h,P=0.75). The median TTP for Gram-negative organisms was 11.17 h (Q1–Q38.84–15.67), whereas the median TTP for Gram-positive organisms was 23.59 h (Q1–Q315.29–34.58,P<0.001). In Gram-positive isolates, the median TTP for coagulase-negative staphylococci (CNS) was 26.67 h (Q1–Q319.00–38.17), whereas the median TTP for non-CNS was 12.83 h (Q1–Q310.50–18.17,P<0.001). The median TTP in proven sepsis was 20.17 h (Q1–Q313.00–30.37), whereas it was 29.67 h (Q1–Q321.17–50.63,P<0.001) in non-proven sepsis. TTP of neonatal blood cultures was significantly shorter for Gram-negative organisms. We suggest shortening the total incubation time of neonatal blood cultures to a maximum of 3 days. However, blood cultures collected in infants <72 h of age might require a longer incubation time. According to our results, it may be safe to narrow the antimicrobial spectrum to solely target Gram-positive bacteria when the culture is still negative after 48 h, and to cease antimicrobial therapy when the culture is still negative after 72 h in clinically well infants.
Haemophagocytic syndrome and rickettsial diseases
Authors: Cascio Antonio , Giordano Salvatore , Dones Piera , Venezia Silvia , Iaria Chiara , Ziino Ottavio
Published: December 2010

Haemophagocytic lymphohistiocytosis is a rare but potentially fatal disease resulting from dysregulated activation and proliferation of lymphocytes. We present a case of haemophagocytic syndrome occurring in a 5-year-old Italian boy as a complication of Mediterranean spotted fever. The characteristics of this case have been analysed and contextualized among those of another 15 cases of haemophagocytic syndrome associated with rickettsial diseases found through a systematic review of the international literature.
bla
CTX-M-65 is carried by a Tn1722-like element on an IncN conjugative plasmid of ST131 Escherichia coli
Authors: Zong Zhiyong , Yu Rujia , Wang Xiaohui , Lü Xiaoju
Published: December 2010

Escherichia coli clinical isolate WCE307 was found to belong to phylogroup B2, O25b and sequence type (ST) 131 and had bla
CTX-M-65, which was carried by an IncN conjugative plasmid, pWCE307. On pWCE307, the ISEcp1Δ-bla
CTX-M-65-IS903D-ironΔ structure was located in a Tn1722-like element flanked by 5 bp direct target repeats. This context was highly similar to that on pKC396, an IncN plasmid from E. coli isolate KC396 of ST131 from Germany. The Tn1722-like elements carrying bla
CTX-M-65 on pWCE307 and pKC396 are likely to be hybrids of Tn1722 and Tn5051, resulting from double crossover at the res sites and the tnpA genes. The left end of the Tn1722-like elements was partially missing. As ISEcp1 and Tn1722 were both incomplete, bla
CTX-M-65 might have been trapped in this context. A plasmid multilocus sequence typing (pMLST) scheme with five targets, repN, stbB, traI, traB and the korB–orfI spacer region, was developed for IncN plasmid typing. pMLST revealed that the five alleles of pWCE307 and pKC396 were identical, indicating that WCE307 and KC396 are likely to have originated very recently from a common strain, suggesting the international spread of bla
CTX-M-65 mediated by ST131 E. coli.
Interactome mapping suggests new mechanistic details underlying Alzheimer's disease
Authors: Soler-López Montserrat , Zanzoni Andreas , Lluís Ricart , Stelzl Ulrich , Aloy Patrick
Published: December 2010

Recent advances toward the characterization of Alzheimer's disease (AD) have permitted the identification of a dozen of genetic risk factors, although many more remain undiscovered. In parallel, works in the field of network biology have shown a strong link between protein connectivity and disease. In this manuscript, we demonstrate that AD-related genes are indeed highly interconnected and, based on this observation, we set up an interaction discovery strategy to unveil novel AD causative and susceptibility genes. In total, we report 200 high-confidence protein–protein interactions between eight confirmed AD-related genes and 66 candidates. Of these, 31 are located in chromosomal regions containing susceptibility loci related to the etiology of late-onset AD, and 17 show dysregulated expression patterns in AD patients, which makes them very good candidates for further functional studies. Interestingly, we also identified four novel direct interactions among well-characterized AD causative/susceptibility genes (i.e.,APP,A2M,APOE,PSEN1, andPSEN2), which support the suggested link between plaque formation and inflammatory processes and provide insights into the intracellular regulation ofAPPcleavage. Finally, we contextualize the discovered relationships, integrating them with all the interaction data reported in the literature, building the most complete interactome associated to AD. This general view facilitates the analyses of global properties of the network, such as its functional modularity, and triggers many hypotheses on the molecular mechanisms implicated in AD. For instance, our analyses suggest a putative role forPDCD4as a neuronal death regulator andECSITas a molecular link between oxidative stress, inflammation, and mitochondrial dysfunction in AD.
Effects of pre-experimental knowledge on recognition memory
Authors: Bird Chris M. , Davies Rachel A. , Ward Jamie , Burgess Neil
Published: December 2010

The influence of pre-experimental autobiographical knowledge on recognition memory was investigated using as memoranda faces that were either personally known or unknown to the participant. Under a dual process theory, such knowledge boosted both recollection- and familiarity-based recognition judgements. Under an unequal variance signal detection model, pre-experimental knowledge increased both the variance and the separation of the target and foil memory strength distributions, boosting hits and correct rejections. Thus, pre-experimental knowledge has profound effects on the multiple, interacting processes that subserve recognition memory, and likely in the neural systems that underpin them.
Distinct pattern separation related transfer functions in human CA3/dentate and CA1 revealed using high-resolution fMRI and variable mnemonic similarity
Authors: Lacy Joyce W. , Yassa Michael A. , Stark Shauna M. , Muftuler L. Tugan , Stark Craig E.L.
Published: December 2010

Producing and maintaining distinct (orthogonal) neural representations for similar events is critical to avoiding interference in long-term memory. Recently, our laboratory provided the first evidence for separation-like signals in the human CA3/dentate. Here, we extended this by parametrically varying the change in input (similarity) while monitoring CA1 and CA3/dentate for separation and completion-like signals using high-resolution fMRI. In the CA1, activity varied in a graded fashion in response to increases in the change in input. In contrast, the CA3/dentate showed a stepwise transfer function that was highly sensitive to small changes in input.
Investigation of the structure and phase transitions of the polymeric inorganic–organic hybrids: [M(Im)4V2O6]∞; M = Mn, Co, Ni, Im = imidazole
Authors: Chainok Kittipong , Haller Kenneth J. , Rae A. David , Willis Anthony C. , Williams Ian D.
Published: December 2010

The polymeric isomorphous hybrid inorganic–organic vanadium oxide compounds [M(Im)4V2O6]∞, M = Mn, Co, Ni, Im = imidazole, were investigated at various temperatures between 100 and 295 K by single-crystal X-ray diffraction. The crystals all contain two-dimensional polymeric sheets packed perpendicular to c* and are 1:1 disordered in the space group P42/n (Z = 8) at 295 K. The disordered phase is reversibly transformed to an I41/a ordered phase (Z = 32) below 281 K for the Mn compound and below 175 K for the Co compound. Within a localized region of the I41/a phase eight imidazoles are in close proximity and seven of these are hydrogen bonded to framework O atoms. The hydrogen-bond connectivity of six of these ligands is unchanged by the phase transition that allows an inversion of the local geometry using an inversion operator that is a symmetry element of P42/n, but not I41/a. The Mn structure has a well defined phase transition but the Co structure shows a large hysteresis and it was necessary to include stacking faults in the modelling of the Co structure at low temperatures. The Ni structure was shown to be partially twinned, but ordered in the space group P2/n (Z = 8) at 100 K, with two different localized regions each containing four pairs of inversion-related imidazoles, hydrogen bonding to framework O atoms involving eight imidazoles in one region and six imidazoles in the other. Models for the phase transition mechanisms are considered.
Disrupted plasma membrane localization of equilibrative nucleoside transporter 2 in the chemoresistance of human pancreatic cells to gemcitabine (dFdCyd)
Authors: Nishio Ren , Tsuchiya Hiroyuki , Yasui Toshihiro , Matsuura Shizuka , Kanki Keita , Kurimasa Akihiro , Hisatome Ichiro , Shiota Goshi
Published: December 2010

Although the nucleoside pyrimidine analogue gemcitabine is the most effective single agent in the palliation of advanced pancreatic cancer, cellular resistance to gemcitabine treatment is a major problem in the clinical scene. To clarify the molecular mechanisms responsible for chemoresistance to gemcitabine, mRNA expression of the key enzymes including cytidine deaminase (CDA), deoxycytidine kinase (dCK), 5′‐nucleotidase (NT5), equilibrative nucleoside transporter 1 and 2 (ENT1 and ENT2), dCMP deaminase (dCMPK), ribonucleotide reductase M1 and M2 (RRM1 and RRM2), thymidylate synthase (TS) and CTP synthase (CTPS) was examined. The interacellular uptake of gemcitabine was greatly impaired in the chemoresistant cell lines due to dysfunction of ENT1 and ENT2. Protein expression of ENT1 and ENT2 and their protein coding sequences were not altered. Immunohistochemical and western blot analyses revealed that localization of ENT2 on the plasma membrane was disrupted. These data suggest that the disrupted localization of ENT2 is one of causes of the impaired uptake of gemcitabine, resulting in a gain of chemoresistance to gemcitabine. (Cancer Sci 2011; 102: 622–629)
Effect of organic matter input on functional pools of soil organic carbon in a long‐term double rice crop experiment in China
Authors: Schulz E. , Breulmann M. , Boettger T. , Wang K.‐R. , Neue H.‐U.
Published: December 2010

It is known that crop residue input has a strong impact on the quantity of soil organic matter (SOM). However, its influence on SOM quality is often unknown. The effect of organic matter (OM) input on soil organic carbon (SOC) and functional SOC pools was investigated in a Chinese long‐term double‐cropping experiment with rice. It could be demonstrated that the C content of hot‐water soil extracts (CHWE) may serve as an indicator of the decomposable SOC pool. A particle size–density fractionation was used to separate SOC pools with different interactions with the mineral soil matrix. The hot‐water C extractability of different particle size‐density fractions, together with their δ13C isotopic signatures, was applied to differentiate stability and potential degradability of SOC pools. The main findings were: first, the input of OM (rice straw + animal manure + green manure) to the unfertilized (Nil) and fertilized (NPK) treatments resulted in a 43–64% increase of SOC over 14 years. Second, during the same period the CHWE pool declined by 25–32% in plots without OM input. Organic amendments reduced the decrease in the CHWE pool by about 50%. Hot‐water‐extractable carbon (C) (CHWE) of bulk soil could serve as an indicator of decomposable SOC pools with the potential for nutrient supply during decomposition. Third, the importance and capacity of smaller‐sized clay particles (CF1 <1 µm) for C storage was proved by large C enrichment factors (ESOC). Fourthly, functional C pools in different size‐density fractions could be clearly separated from each other according to their stability, by relating the 13C isotopic abundance of C pools to the hot‐water‐extractable component (δ13C*fraction).
Combined immunohistochemistry for the differential diagnosis of cystic jaw lesions: its practical use in surgical pathology
Authors: Tsuneki Masayuki , Yamazaki Manabu , Cheng Jun , Maruyama Satoshi , Kobayashi Takanori , Saku Takashi
Published: December 2010

Tsuneki M, Yamazaki M, Cheng J, Maruyama S, Kobayashi T & Saku T (2010) Histopathology57, 806–813

Combined immunohistochemistry for the differential diagnosis of cystic jaw lesions: its practical use in surgical pathology

Aims:  Histopathological distinction of cystic jaw lesions, including odontogenic tumours, is challenging because their lining epithelia, which are basically stratified squamous epithelia, resemble each other, especially when they become hyperplastic from inflammatory reaction. The aim of this study was to seek practical measures to differentiate such lesions.

Methods and results:  Nineteen surgical specimens from unicystic ameloblastomas (UAs), 17 from keratocystic odontogenic tumours (KCOTs), 13 from dentigerous cysts (DCs), 10 from lateral periodontal cysts (LPCs) and 20 from radicular cysts (RCs), all of which contained both typical flat and rete‐peg‐shaped lining epithelia, were examined for their immunohistochemical profiles. Among them, keratin (K) 10, K17, perlecan, proliferating cell nuclear antigen (PCNA) and UEA‐I lectin binding (UEA) were selected as useful immunohistochemical markers for their differential diagnosis. K10 was positive (+) in KCOT and DC. K17 was not present in RC. Perlecan was found in UA, KCOT and LPC. PCNA+ cells were found frequently in UA and KCOT. These localization patterns were constant even when linings were not flat.

Conclusions:  Using a combination of six kinds of immunohistochemical pattern, it is now possible to discriminate reliably and objectively these five cystic jaw lesions in routine practice.
De novo expression of EphA2 in osteosarcoma modulates activation of the mitogenic signalling pathway
Authors: Fritsche‐Guenther Raphaela , Noske Aurelia , Ungethüm Ute , Kuban Ralf‐Jürgen , Schlag Peter M. , Tunn Per‐Ulf , Karle Janine , Krenn Veit , Dietel Manfred , Sers Christine
Published: December 2010

Fritsche‐Guenther R, Noske A, Ungethüm U, Kuban R‐J, Schlag PM, Tunn P‐U, Karle J, Krenn V, Dietel M & Sers C (2010) Histopathology57, 836–850

De novo expression of EphA2 in osteosarcoma modulates activation of the mitogenic signalling pathway

Aims:  In osteosarcoma patients the development of metastases, often to the lungs, is the most frequent cause of death. The aim of this study was to elucidate the molecular mechanisms governing osteosarcoma development and dissemination and, thereby, to identify possible novel drug targets for improved treatment.

Methods and results:  Osteosarcoma samples were characterized using genome‐wide microarrays: increased expression of the EphA2 receptor and its ligand EFNA1 was detected. In addition, increased expression of EFNB1, EFNB3 and EphA3 was suggested. Immunohistochemistry revealed an absence of EphA2 in normal bone, and de novo expression in osteosarcomas. EFNA1 was expressed in normal bone, but was significantly elevated in tumours. Further in vitro investigations on the functional role of EphA2 and EFNA1 showed that EFNA1 ligand binding induced increased tyrosine phoshorylation, receptor degradation and downstream mitogen‐activated protein kinase (MAPK) activation. Interference with the MAPK pathway unravelled a potential autoregulatory loop governing mainly EFNA1 expression via the same pathway.

Conclusion:  Upregulation and de novo expression of ephrins in osteosarcomas are involved in oncogenic signalling and thus might stimulate osteosarcoma metastasis.
Loss of BCL2L10 protein expression as prognostic predictor for poor clinical outcome in gastric carcinoma
Authors: Xu Jing Da , Furuya Tomoko , Cao Xi Xi , Liu Xiao Li , Li Qing Quan , Wang Wen Juan , Xu Jia Wen , Xu Zu De , Sasaki Kohsuke , Liu Xiu Ping
Published: December 2010

Xu J D, Furuya T, Cao X X, Liu X L, Li Q Q, Wang W J, Xu J W, Xu Z D, Sasaki K & Liu X P (2010) Histopathology57, 814–824

Loss of BCL2L10 protein expression as prognostic predictor for poor clinical outcome in gastric carcinoma

Aims:  BCL2L10 protein is an apoptosis‐related member of the Bcl‐2 protein family. The clinical significance of its expression in gastric carcinoma is poorly understood. The aim was to investigate BCL2L10 expression and its clinical and prognostic significance in gastric carcinoma patients.

Methods and results:  Immunohistochemistry, real–time polymerase chain reaction (PCR) and immunoblotting all revealed extensive loss of BCL2L10 expression in gastric cancer cells. The scaled BCL2L10 expression data was categorized into three groups (groups 0–2) to facilitate statistical analysis. A significant correlation was observed between the lower BCL2L10 expression group and shorter disease‐free survival (P = 1.956 × 10−18). Multivariate regression analysis showed that loss of BCL2L10 protein expression [P = 4.883 × 10−8, hazard ratio (HR) = 0.252] is an independent prognostic predictor of gastric carcinoma. The receiver operator characteristic (ROC) curve showed that the area for BCL2L10 protein was 0.817 (P = 8.331 × 10−14), indicating that loss of BCL2L10 protein expression is an excellent prognostic predictor of gastric carcinoma.

Conclusions:  Loss of BCL2L10 protein expression predicts poor clinical outcome in gastric carcinoma.
Association of mast cell, eosinophil leucocyte and microvessel densities in actinic cheilitis and lip squamous cell carcinoma
Authors: Souza Ludmilla R , Fonseca‐Silva Thiago , Santos Carolina C O , Oliveira Marcos V M , Corrêa‐Oliveira Rodrigo , Guimarães André L S , De Paula Alfredo M B
Published: December 2010

Souza L R, Fonseca‐Silva T, Santos C C O, Oliveira M V M, Corrêa‐Oliveira R, Guimarães A L S & De Paula A M B (2010) Histopathology57, 796–805

Association of mast cell, eosinophil leucocyte and microvessel densities in actinic cheilitis and lip squamous cell carcinoma

Aims:  To determine the contributions of mast cells (MC), eosinophil leucocytes (EL) and microvessel density (MVD) in lip carcinogenesis, and to establish the relationships between these biomarkers and their possible prognostic value in lip squamous cell carcinoma (LSCC).

Methods and results:  Archived specimens of lip mucosa (n = 13), actinic cheilitis (n = 29) and LSCC (n = 29) were formalin‐fixed, paraffin‐embedded, sectioned and stained with toluidine blue and haematoxylin and eosin (H&E) in order to identify MC and EL and to measure their densities. Tumour angiogenesis was estimated by determining, with the use of CD31 antibody MVD in areas with the highest number of stained microvessels (‘hot spots’). Progressive increases of MC, EL and MVD were observed during lip tumour development. Correlation analysis revealed positive associations between the biomarkers during tumour progression. In LSCC samples, significant associations were found between MVD values and metastatic disease. On multivariate analysis, MVD was a predictor of risk of cervical metastasis.

Conclusions:  The densities of MC, EL and microvessels increase during lip carcinogenesis, and for MC and EL this may be related to the stimulation of tumour angiogenesis. MVD could be a useful predictor of cervical metastasis in LSCC.
Androgen receptor expression in breast cancer patients tested for BRCA1 and BRCA2 mutations
Authors: Pristauz Gunda , Petru Edgar , Stacher Elvira , Geigl Jochen B , Schwarzbraun Thomas , Tsybrovskyy Oleksiy , Winter Raimund , Moinfar Farid
Published: December 2010

Pristauz G, Petru E, Stacher E, Geigl J B, Schwarzbraun T, Tsybrovskyy O, Winter R & Moinfar F (2010) Histopathology57, 877–884

Androgen receptor expression in breast cancer patients tested for BRCA1 and BRCA2 mutations

Aim:  To assess the expression of receptors for androgen (AR), oestrogen (ER) and progesterone (PR) as well as human epidermal growth factor receptor type 2 (Her‐2/neu) status of breast carcinomas in breast cancer susceptibility gene (BRCA) BRCA1/2 mutation carriers and BRCA1/2 negative tested women.

Methods:  One hundred and thirty‐five breast cancers in women tested for BRCA1/2 mutations. Screening for BRCA1 and BRCA2 mutations was performed by direct sequencing of all BRCA1 and BRCA2 exons as well as the surrounding intronic sequences. Additionally, BRCA genes were analysed with multiplex ligation‐dependent probe amplification. Consecutive paraffin sections were examined immunhistochemically for AR, ER, PR and Her‐2/neu.

Results:  Of the 135 tumours, 43 (32%) were BRCA1‐related, 18 (13%) were BRCA2‐related and 74 (55%) were BRCA1/2‐negative. Seventy‐two per cent of the BRCA1‐related, 22% of the BRCA2‐related and 12% of the BRCA1/2‐negative tumours were triple (ER, PR, Her2neu)‐negative. Eighty‐four per cent of BRCA1 mutated cancers were high‐grade (G3) tumours. ARs were expressed in 30% (13 of 43) of BRCA1‐related, in 78% (14 of 18) in BRCA2‐related tumours and in 76% (56 of 74) in BRCA1/2 negative tumours. Twenty‐one per cent of ER‐negative BRCA1‐related tumours expressed androgen receptors.

Conclusion:  Approximately one in five BRCA1 mutated breast cancers negative for ER and PR express androgen receptors. Modulation of AR might open a new avenue for treating these high‐risk cancers.
Primary squamous cell carcinoma of the vagina: human papillomavirus detection, p16INK4A overexpression and clinicopathological correlations
Authors: Fuste Victoria , del Pino Marta , Perez Assumpta , Garcia Angel , Torne Aureli , Pahisa Jaume , Ordi Jaume
Published: December 2010

Fuste V, del Pino M, Perez A, Garcia A, Torne A, Pahisa J & Ordi J (2010) Histopathology57, 907–916

Primary squamous cell carcinoma of the vagina: human papillomavirus detection, p16

INK4A

overexpression and clinicopathological correlations

Aim:  To determine the role of human papillomavirus (HPV) in the pathogenesis of primary squamous cell carcinoma of the vagina (SCCVa), and to evaluate its clinicopathological significance.

Methods and results:  All cases of SCCVa diagnosed over a 15‐year period from two hospitals in Barcelona, Spain (n = 32) were retrieved. Patients with a history of carcinoma of the cervix diagnosed <5 years before were excluded. HPV was detected and typed by polymerase chain reaction (PCR) using SPF10 primers. Immunohistochemistry was performed for p16 and p53. HPV was detected in 25 cases (78.1%). HPV16 was the most prevalent type. Patients with HPV‐positive tumours were associated frequently with a history of carcinoma or intraepithelial neoplasia of the cervix or vulva diagnosed more than 5 years before (56% versus 0%; P = 0.01). HPV‐positive tumours were more frequently of non‐keratinizing, basaloid or warty type than HPV‐negative neoplasms (84% versus 14.3%; P < 0.001), and showed diffuse positive immunoreactivity for p16INK4a (96%, versus 14.3%; P < 0.001). The sensitivity and specificity of p16 to identify HPV‐positive tumours were 96% and 85.7%, respectively.

Conclusions:  A high number of SCCVs are related to HPV infection and may be identified by immunohistochemistry for p16. HPV‐positive tumours tend to affect women with history of cervical neoplasia.
Conventional and surgical endodontic treatment of a maxillary first molar with unusual anatomy – a case report
Authors: Floratos S. , Kratchman S. I.
Published: December 2010

Floratos S, Kratchman SI. Conventional and surgical endodontic treatment of a maxillary first molar with unusual anatomy – a case report. International Endodontic Journal.

Aim  To describe conventional and surgical endodontic treatment of a maxillary left first molar with two canals on the distobuccal root and to discuss the treatment outcome.

Summary  According to the literature, the presence of a second canal on the distobuccal root of a maxillary first molar is rare. This anatomical anomaly might lead to an unfavourable outcome if clinicians fail to identify and treat it properly. The following case report describes conventional and surgical endodontic treatment of a maxillary left first molar with two canals on the distobuccal root.

Key learning points 

Anatomical variations of the root canal system are a challenge for clinicians during root canal retreatment.

The principles and techniques of endodontic microsurgery are of utmost importance in clinical practice, and clinicians should be aware of them.
Using presence‐only and presence–absence data to estimate the current and potential distributions of established invasive species
Authors: Gormley Andrew M. , Forsyth David M. , Griffioen Peter , Lindeman Michael , Ramsey David S.L. , Scroggie Michael P. , Woodford Luke
Published: December 2010

1. Predicting the current and potential distributions of established invasive species is critical for evaluating management options, but methods for differentiating these distributions have received little attention. In particular, there is uncertainty among invasive species managers about the value of information from incidental sightings compared to data from designed field surveys. This study compares the two approaches, and develops a unifying framework, using the case of invasive sambar deerCervus unicolorin Victoria, Australia.

2. We first used 391 incidental sightings of sambar deer and 12 biophysical variables to construct a presence‐only habitat suitability model using Maxent. We then used that model to stratify field sampling, with proportionately greater sampling of cells with high predicted habitat suitability. Field sampling, consisting of faecal pellet surveys, sign surveys and camera trapping, was conducted in 80 4‐km2grid cells. A Bayesian state‐space occupancy model was used to predict probability of suitable habitat from the field data.

3. The Maxent and occupancy models predicted similar spatial distributions of habitat suitability for sambar deer in Victoria and there was a strong positive correlation between the rankings of cells by the two approaches. The congruence of the two models suggests that any spatial and detection biases in the presence‐only data were relatively unimportant in our study.

4. We predicted the extent of suitable habitat from the occupancy model using a threshold that gave a false negative error rate of 0·05. The current distribution was the suitable habitat within a kernel that had a 99·5% chance of including the presence locations pooled from incidental sightings and field surveys: the potential distribution was suitable habitat outside that kernel. Several discrete areas of potential distribution were identified as priorities for surveillance monitoring with the aim of detecting and managing incursions of sambar deer.

5. Synthesis and applications. Our framework enables managers to robustly estimate the current and potential distributions of established invasive species using either presence‐only and/or presence–absence data. Managers can then focus control and/or containment actions within the current distribution and establish surveillance monitoring to detect incursions within the potential distribution.
Modelling community dynamics based on species‐level abundance models from detection/nondetection data
Authors: Yamaura Yuichi , Andrew Royle J. , Kuboi Kouji , Tada Tsuneo , Ikeno Susumu , Makino Shun’ichi
Published: December 2010

1. In large‐scale field surveys, a binary recording of each species’ detection or nondetection has been increasingly adopted for its simplicity and low cost. Because of the importance of abundance in many studies, it is desirable to obtain inferences about abundance at species‐, functional group‐, and community‐levels from such binary data.

2. We developed a novel hierarchical multi‐species abundance model based on species‐level detection/nondetection data. The model accounts for the existence of undetected species, and variability in abundance and detectability among species. Species‐level detection/nondetection is linked to species‐level abundance via a detection model that accommodates the expectation that probability of detection (at least one individuals is detected) increases with local abundance of the species. We applied this model to a 9‐year dataset composed of the detection/nondetection of forest birds, at a single post‐fire site (from 7 to 15 years after fire) in a montane area of central Japan. The model allocated undetected species into one of the predefined functional groups by assuming a prior distribution on individual group membership.

3. The results suggest that 15–20 species were missed in each year, and that species richness of communities and functional groups did not change with post‐fire forest succession. Overall abundance of birds and abundance of functional groups tended to increase over time, although only in the winter, while decreases in detectabilities were observed in several species.

4. Synthesis and applications. Understanding and prediction of large‐scale biodiversity dynamics partly hinge on how we can use data effectively. Our hierarchical model for detection/nondetection data estimates abundance in space/time at species‐, functional group‐, and community‐levels while accounting for undetected individuals and species. It also permits comparison of multiple communities by many types of abundance‐based diversity and similarity measures under imperfect detection.
Divergent Protein Kinase A isoforms co‐ordinately regulate conidial germination, carbohydrate metabolism and virulence in Aspergillus fumigatus
Authors: Fuller Kevin K. , Richie Daryl L. , Feng Xizhi , Krishnan Karthik , Stephens Timothy J. , Wikenheiser‐Brokamp Kathryn A. , Askew David S. , Rhodes Judith C.
Published: December 2010

The genome of Aspergillus fumigatus encodes two isoforms of the catalytic subunit of the cAMP‐dependent Protein Kinase (PKA). Although deletion of the class I isoform, pkaC1, leads to an attenuation of virulence, the function of the class II subunit, PkaC2, was previously uninvestigated. In this report, we demonstrate that both isoforms act in concert to support various physiologic processes that promote the virulence of this pathogen. Whereas pkaC1 and pkaC2 single‐deletion mutants display wild‐type conidial germination, a double‐deletion mutant is delayed in germination in response to environmental nutrients. Furthermore, PkaC1 and PkaC2 interact to positively regulate flux through the carbohydrate catabolic pathway and, consequently, the ΔpkaC1ΔpkaC2 mutant is unable to grow on low glucose concentrations. Importantly, the reduced germinative capacity and inability to utilize glucose observed for the ΔpkaC1ΔpkaC2 strain correlated with an inability of the mutant to establish infection in a murine model. Conversely, overexpression of pkaC2 both promotes the in vitro growth on glucose, and restores the fungal burden and mortality associated with the ΔpkaC1 to that of the wild‐type organism. Taken together, these data demonstrate the functional capacity of pkaC2 and emphasize the importance of PKA‐mediated metabolic control in the pathogenic potential of A. fumigatus.
Cell surface display of minor pilin adhesins in the form of a simple heterodimeric assembly in Corynebacterium diphtheriae
Authors: Chang Chungyu , Mandlik Anjali , Das Asis , Ton‐That Hung
Published: December 2010

Pilus assembly in Gram‐positive bacteria occurs by a two‐step mechanism, whereby pilins are polymerized and then covalently anchored to the cell wall. In Corynebacterium diphtheriae, the pilin‐specific sortase SrtA catalyses polymerization of the SpaA‐type pilus, consisting of the shaft pilin SpaA, tip pilin SpaC and minor pilin SpaB. Cell wall anchoring of the SpaA polymers is triggered when SrtA incorporates SpaB into the pilus base via lysine‐mediated transpeptidation; anchoring to the cell wall peptidoglycan is subsequently catalysed by the housekeeping sortase SrtF. Here we show that SpaB and SpaC formed a heterodimer independent of SpaA polymerization. SrtA was absolutely required for the formation of the SpaBC heterodimer, while SrtF facilitated the optimal cell wall anchoring of this heterodimer. Alanine substitution of the SpaB lysine residue K139 or truncation of the SpaB cell wall‐sorting signal (CWSS) abolished assembly of the SpaBC heterodimer, hence underscoring SpaB function in transpeptidation and cell wall linkage. Importantly, sortase specificity for the cell wall‐anchoring step was found to be dependent on the LAFTG motif within the SpaB CWSS. Thus, C. diphtheriae employs a common sortase‐catalysed mechanism involving lysine‐mediated transpeptidation to generate both adhesive pilus and simple heterodimeric structures on the bacterial the cell wall.
The Pseudomonas aeruginosa flagellum confers resistance to pulmonary surfactant protein‐A by impacting the production of exoproteases through quorum‐sensing
Authors: Kuang Zhizhou , Hao Yonghua , Hwang Sunghei , Zhang Shiping , Kim Eunice , Akinbi Henry T. , Schurr Michael J. , Irvin Randall T. , Hassett Daniel J. , Lau Gee W.
Published: December 2010

Surfactant protein‐A (SP‐A) is an important antimicrobial protein that opsonizes and permeabilizes membranes of microbial pathogens in mammalian lungs. Previously, we have shown that Pseudomonas aeruginosa flagellum‐deficient mutants are preferentially cleared in the lungs of wild‐type mice by SP‐A‐mediated membrane permeabilization, and not by opsonization. In this study, we report a flagellum‐mediated mechanism of P. aeruginosa resistance to SP‐A. We discovered that flagellum‐deficient (ΔfliC) bacteria are unable to produce adequate amounts of exoproteases to degrade SP‐A in vitro and in vivo, leading to its preferential clearance in the lungs of SP‐A+/+ mice. In addition, ΔfliC bacteria failed to degrade another important lung antimicrobial protein lysozyme. Detailed analyses showed that ΔfliC bacteria are unable to upregulate the transcription of lasI and rhlI genes, impairing the production of homoserine lactones necessary for quorum‐sensing, an important virulence process that regulates the production of multiple exoproteases. Thus, reduced ability of ΔfliC bacteria to quorum‐sense attenuates production of exoproteases and limits degradation of SP‐A, thereby conferring susceptibility to this major pulmonary host defence protein.
Descensus and Development: A Response to Recent Rejoinders
Authors: OAKES EDWARD T.
Published: December 2010

Two articles were published in this journal in 2009 responding to and criticizing my 2007 article on Hans Urs von Balthasar's theology of Holy Saturday. The article below responds to those critiques by establishing the following points: (1) Balthasar's theology of Christ's expiatory descent into hell (that is, one in which Christ's human soul suffered the pains of hell) is thoroughly traditional and can be found asserted throughout theological literature; (2) on the question of (the possibility of) universal salvation, the development from Augustine's consigning of the majority of the human race to hell to Vatican II's assertion that all human beings are connected to the paschal mystery took place independently of Balthasar's theology (a development which of course he accepts), and thus to criticize him on this point is implicitly to deny the very rules for authentic development as outlined by John Henry Newman that both my interlocutors claim to accept.
Effects of visual processing and congenital nystagmus on visually guided ocular motor behaviour
Authors: PEL JOHAN , DOES LISETTE VAN DER , BOOT FLEUR , FABER TJEERD DE , STEEN‐KANT SANNY VAN DER , WILLEMSEN STEN , STEEN HANS VAN DER
Published: December 2010

Aim  The aim of this study was to compare visually guided ocular motor behaviour in children with visual processing and/or motor deficits with an age‐matched comparison group and an adult group.

Method  Visual stimuli were shown to 28 children with visual processing and/or motor deficits (11 females, 17 males; mean age 7y 5mo, SD 2y 9mo, range 2–14y;) and an age‐matched comparison group of 213 typically developing children (115 females, 98 males; mean age 5y 8mo, SD 3y 5mo, range 0–12y). The adult group consisted of nine females and two males with (mean age of 24y 4mo, SD 4y 8mo). Individuals who had a likely diagnosis of cerebral visual impairment (CVI), an opticopathy with unknown location, nystagmus, glaucoma, or a cataract were included in the study. Exclusion criteria were a visual acuity below 0.2, a developmental age under 1 year, and the presence of brain tumours, autism, and anxiety disorders. Orientating eye movements to large cartoons were quantified using the reaction time to fixation (RTF) and gaze fixation area (GFA). A Mann–Whitney U test was used to compare the differences between groups and Bonferroni post‐hoc testing was used to analyse age dependence of RTF and GFA values within the comparison group.

Results  Individuals with CVI showed significantly prolonged RTF values; those with congenital nystagmus showed significantly increased GFA values. In the comparison group, RTF was significantly longer in children under the age of 2 years than in children aged 4 years and older (290 and 200ms respectively; p<0.001). No developmental change was found for GFA values.

Interpretation  Increased RTF values in individuals with CVI relate to visual processing deficits. The data suggest that visually guided ocular motor responses mature during the first 3 years of life.
FLUORESCENCE EMISSION SPECTRA OF MARINE AND BRACKISH‐WATER ECOTYPES OF FUCUS VESICULOSUS AND FUCUS RADICANS (PHAEOPHYCEAE) REVEAL DIFFERENCES IN LIGHT‐HARVESTING APPARATUS1
Authors: Maria Gylle Anna , Rantamäki Susanne , Ekelund Nils G. A. , Tyystjärvi Esa
Published: December 2010

The Bothnian Sea in the northerly part of the Baltic Sea is a geologically recent brackish‐water environment, and rapid speciation is occurring in the algal community of the Bothnian Sea. We measured low‐temperature fluorescence emission spectra from the Bothnian Sea and the Norwegian Sea ecotypes of Fucus vesiculosus L., a marine macroalga widespread in the Bothnian Sea. Powdered, frozen thallus was used to obtain undistorted emission spectra. The spectra were compared with spectra measured from the newly identified species Fucus radicans Bergström et L. Kautsky, which is a close relative of F. vesiculosus and endemic to the Bothnian Sea. The spectrum of variable fluorescence was used to identify fluorescence peaks originating in PSI and PSII in this chl c–containing alga. The spectra revealed much higher PSII emission, compared to PSI emission, in the Bothnian Sea ecotype of F. vesiculosus than in F. radicans or in the Norwegian Sea ecotype of F. vesiculosus. The results suggest that more light‐harvesting chl a/c proteins serve PSII in the Bothnian Sea ecotype of F. vesiculosus than in the two other algal strains. Treatment of the Bothnian Sea ecotype of F. vesiculosus in high salinity (10, 20, and 35 practical salinity units) for 1 week did not lead to spectral changes, indicating that the measured features of the Bothnian Sea F. vesiculosus are stable and not simply a direct result of exposure to low salinity.
Analysis of differentially expressed proteins in oral squamous cell carcinoma by MALDI‐TOF MS
Authors: Thiel Uta J. E. , Feltens Ralph , Adryan Boris , Gieringer Rita , Brochhausen Christoph , Schuon Robert , Fillies Thomas , Grus Franz , Mann Wolf J. , Brieger Juergen
Published: December 2010

J Oral Pathol Med (2010) 40: 369–379

Purpose:  To explore the presence of differentially expressed proteins in OSCC for discrimination of tumour and normal mucosa to establish potential biomarkers and therapeutic targets.

Experimental Design:  Paired protein samples of 12 individuals (tongue cancer and non‐cancerous mucosa) were separated by two‐dimensional polyacrylamid gel electrophoresis. The protein patterns were compared pairwise and protein spots were quantified. We identified about 70 regulated proteins which we subsequently identified by MALDI‐TOF mass spectrometry.

Results:  Cancerous and non‐cancerous tissues could be most precisely distinguished by a panel of proteins. They include the heat shock proteins (hsp)70 and 90, keratins (ck) 5, 6, 13, 14, 16, 17 and 19, beta globin, alpha‐2‐actin, stratifin, tropomyosin, calreticulin precursor, beta‐2‐tubulin, galectin7, thioredoxin, involucrin, adenylyl‐cyclase‐associated protein, disulfide isomerase‐associated protein, thyrosine 3‐monooxygenase, MYL2 and the s100 calcium binding protein. MYL3, cardiac muscle alpha actin 1 proprotein and transferrin were under‐represented in OSCC. Six biomarkers, ck6 und ck13, beta globin, alpha‐2‐actin, hsp70 and hsp90 discriminated best between cancerous and non‐cancerous oral tissues. All over‐expressed proteins were analysed by STRING‐analysis to highlight experimentally determined and computationally predicted interactions between the proteins. Especially involucrin, hsp70, calreticulin precursor, stratifin, (ck) 5, 6, 14, 19, tyrosine 3‐monooxygenase, beta‐2‐tubulin and disulfide isomerase associated protein showed multiple relations.

Conclusion:  We identified six proteins which are differentially expressed in most OSCC compared to healthy tissues. Of those, by string analysis, multiple interaction partners are assumed for hsp70. This protein is supposed to be the most promising candidate as marker molecule and target for OSCC therapy.