bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation of tumor growth suppression and methionine aminopetidase-2 activity blockade using an orally active inhibitor
Authors: Wang Jieyi , Tucker Lora A. , Stavropoulos Jason , Zhang Qian , Wang Yi-Chun , Bukofzer Gail , Niquette Amanda , Meulbroek Jonathan A. , Barnes David M. , Shen Jianwei , Bouska Jennifer , Donawho Cherrie , Sheppard George S. , Bell Randy L.
Published: February 2008

This laboratory and others have shown that agents that inhibit the
in vitro
catalytic activity of methionine aminopeptidase-2 (MetAP2) are effective in blocking angiogenesis and tumor growth in preclinical models. However, these prototype MetAP2 inhibitors are clearly not optimized for therapeutic use in the clinic. We have discovered an orally active class of MetAP2 inhibitors, the anthranilic acid sulfonamides exemplified by A-800141, which is highly specific for MetAP2. This orally bioavailable inhibitor exhibits an antiangiogenesis effect and a broad anticancer activity in a variety of tumor xenografts including B cell lymphoma, neuroblastoma, and prostate and colon carcinomas, either as a single agent or in combination with cytotoxic agents. We also have developed a biomarker assay to evaluate
in vivo
MetAP2 inhibition in circulating mononuclear cells and in tumors. This biomarker assay is based on the
N
-terminal methionine status of the MetAP2-specific substrate GAPDH in these cells. In cell cultures
in vitro
, the sulfonamide MetAP2 inhibitor A-800141 caused the formation of GAPDH variants with an unprocessed N-terminal methionine. A-800141 blocked tumor growth and MetAP2 activity in a similar dose–response in mouse models, demonstrating the antitumor effects seen for A-800141 are causally connected to MetAP2 inhibition
in vivo
. The sulfonamide MetAP2 inhibitor and GAPDH biomarker in circulating leukocytes may be used for the development of a cancer treatment.
Relationships of maximal single‐ and double‐step length tests with sex and the dominant and non‐dominant legs
Authors: Demura Shin‐Ichi , Yamada Takayoshi
Published: February 2008

The maximal step length test has been proposed to evaluate the risk of falls among the elderly, although the test is confusing and prone to errors due to two types of test methods. The maximal double‐step length test may be used to evaluate both leg function and the functional difference between the left and right legs, but its measurement and evaluation methods have not been studied extensively. The aims of the present study were to compare the maximal single‐ and double‐step length tests, and to highlight differences between the sexes and between the dominant and non‐dominant legs. Fifty healthy adults free from lower‐limb disorders conducted the above step tests twice, once with the dominant and once with the non‐dominant leg. The former test requires individuals to return the stepping leg to the original position or to draw the other leg to the step leg after stepping out maximally with either leg from a standing posture while maintaining body stability with the supporting leg. The latter test requires individuals to step forward with either leg maximally, after similarly stepping with the other leg and to draw the first stepping leg to the second stepping leg. The above tests are defined as the single‐ and double‐step length test, respectively. Step lengths were measured in both tests, and these values were used for analysis. Correlations among step length tests conducted with the dominant and non‐dominant legs were very high (r=0.82–0.97). Significant sex differences were found in all step length tests, and males were superior to females. No significant difference between legs was found in any test. In summary, the relationship between the maximal single‐ and double‐step length tests was very high and step lengths showed a significant sex difference.
Transforming growth factor β derived from bone matrix promotes cell proliferation of prostate cancer and osteoclast activation‐associated osteolysis in the bone microenvironment
Authors: Sato Shinya , Futakuchi Mitsuru , Ogawa Kumiko , Asamoto Makoto , Nakao Kimihisa , Asai Kiyofumi , Shirai Tomoyuki
Published: February 2008

Metastatic prostate tumors in the bone microenvironment stimulate bone resorption, resulting in release of growth factors from the bone matrix that play important roles in tumor growth and osteoclast induction. Transforming growth factor β (TGFβ) is one of the most abundantly stored cytokines in bone matrix, regulating diverse biological activities. Here we evaluate its involvement in prostate tumor growth in the bone microenvironment, comparing with tumor growth in the subcutaneous microenvironment as a control. Rat prostate tumors were transplanted onto the cranial bone and into the subcutis of F344 male rats. Tumor cell proliferation, apoptosis, and TGFβ signal transduction were compared between the tumor–bone interface and the tumor–subcutaneous interface. Effects of TGFβ on osteoclast differentiation were also evaluated in vitro. Inhibitory effects of TGFβ receptor 1 antisense oligonucleotide on TGFβ signaling, osteolysis, osteoblasts, and tumor growth were examined in vivo. Osteolytic changes were extensively observed at the tumor–bone interface, where the TGFβ level, TGFβ signal transduction, and tumor cell proliferation were higher than at the tumor–subcutaneous interface. In vitro treatment with receptor activator of nuclear factor‐κB ligand induced osteoclast differentiation of bone marrow stromal cells, and additional exposure to TGFβ exerted promotive effects on osteoclast induction. Intratumoral injection of TGFβ receptor 1 antisense oligonucleotide significantly reduced TGFβ signal transduction, osteolysis, induction of osteoclast and osteoblast, and tumor cell proliferation. Thus, we experimentally show that TGFβ derived from bone matrix promotes cell proliferation of rat prostate cancer and osteoclast activation‐associated osteolysis in the bone microenvironment. (Cancer Sci 2008; 99: 316–323)
Downregulation of ING3 mRNA expression predicts poor prognosis in head and neck cancer
Authors: Gunduz Mehmet , Beder Levent Bekir , Gunduz Esra , Nagatsuka Hitoshi , Fukushima Kunihiro , Pehlivan Davut , Cetin Eren , Yamanaka Noboru , Nishizaki Kazunori , Shimizu Kenji , Nagai Noriyuki
Published: February 2008

Although many clinical and pathological prognostic factors such as tumor stage and lymph‐node involvement have been described, to date no reliable or clinically applicable marker or tumor aggressiveness has been identified for head and neck cancer. In an attempt to identify such a molecular prognostic marker, we analyzed the mRNA expression status of ING3 by quantitative reverse transcription–polymerase chain reaction. We also examined p53 mutation status and investigated its relationship with ING3, as well its clinicopathological characteristics. About half of the 71 tumor samples demonstrated downregulation of ING3 compared to their matched normal counterparts. Although most clinicopathological variables were not significantly related to ING3 downregulation or p53 mutation status, a significant relationship was detected in terms of overall survival between the cases with low and normal to high ING3 expression. At 5 years follow up, approximately 60% of the patients with normal to high ING3 expression survived, whereas this was 35% in the patients with low ING3 expression. Multivariate analysis also showed downregulation of ING3 as an independent prognostic factor for poor overall survival. These results reveal that ING3 would function as a potential tumor suppressor molecule and that low levels of ING3 may indicate an aggressive nature of head and neck cancer. (Cancer Sci 2008; 99: 531–538)
Genetic polymorphisms of cyclooxygenase‐2 and colorectal adenoma risk: The Self Defense Forces Health Study
Authors: Ueda Naoyuki , Maehara Yoshihiko , Tajima Osamu , Tabata Shinji , Wakabayashi Keiji , Kono Suminori
Published: February 2008

Cyclooxygenase (COX) is a key enzyme in the formation of prostaglandins, and an inducible isoform of COX, COX‐2, has been implicated in colorectal carcinogenesis. This study investigated the relation of COX‐2 polymorphisms (–1195G>A, –765G>C and 8160A>G) to colorectal adenomas in a case–control study of male officials in the Self Defense Forces (SDF). The study subjects were 455 cases of colorectal adenoma and 1052 controls with no polyps who underwent total colonoscopy. Genotypes were determined using the polymerase chain reaction–restriction fragment length polymorphism (PCR‐RFLP) method with genomic DNA extracted from the buffy coat. Statistical adjustment was made for age, hospital, rank in the SDF, body mass index (BMI), cigarette smoking, and alcohol intake. A statistically non‐significant decrease in the risk of colorectal adenomas was observed for the AA versus GG genotype of –1195G>A polymorphism and for the GC versus GG genotype of –765G>C polymorphism. None had the –765CC genotype in either the case or control groups. No effect modification of overweight, smoking or alcohol use was observed for either –1195G>A or –765G>C polymorphism. The variant allele of the 8160A>G polymorphism was extremely rare. A haplotype of –1195G, –765G and 8160A alleles was associated with a modest increase in the risk (adjusted odds ratio [OR] 1.38, 95% confidence interval [CI] 0.99–1.91), and the increase was more evident for distal adenomas (adjusted OR 1.57, 95% CI 1.04–2.38). Another haplotype of –1195A, –765C and 8160A alleles showed an adjusted OR of 0.22 (95% CI 0.06–0.88). These findings add to evidence for the role of COX‐2 in colorectal carcinogenesis and warrant further studies focusing on haplotypes. (Cancer Sci 2008; 99: 576–581)
Targeting Slit–Roundabout signaling inhibits tumor angiogenesis in chemical‐induced squamous cell carcinogenesis
Authors: Wang Li‐Jing , Zhao Yuan , Han Bing , Ma Yu‐Guang , Zhang Jie , Yang Ding‐Ming , Mao Jian‐Wen , Tang Fu‐Tian , Li Wei‐Dong , Yang Yang , Wang Rui , Geng Jian‐Guo
Published: February 2008

Slit is a secreted protein known to function through the Roundabout (Robo) receptor as a repellent for axon guidance and neuronal migration, and as an inhibitor in leukocyte chemotaxis. We have previously shown that Slit2 is also secreted by a variety of human cancer cells whereby it acts as a chemoattractant to vascular endothelial cells for tumor angiogenesis. We used a blocking antibody to investigate the role of Slit–Robo signaling in tumor angiogenesis during oral carcinogenesis. In this report we undertook a multistage model of 7,12‐dimethyl‐1,2‐benzanthracene‐induced squamous cell carcinoma in the hamster buccal pouch. R5, a monoclonal antibody against the first immunoglobulin domain of Robo1, was used to study whether R5 blocks the Slit–Robo interaction and furthermore inhibits tumor angiogenesis and growth in our model. In addition, the expression of Slit2, von Willebrand factor, and vascular endothelial growth factor were examined using human tissue of oral cheek mucosa with oral squamous cell carcinoma. Our data showed that Slit2 was expressed minimally in normal and hyperplastic mucosa, moderately in dysplastic mucosa, and highly in neoplastic mucosa obtained from hamster buccal pouch. We also found that increased Slit2 expression was associated with higher tumor angiogenesis, as reflected by increased vascular endothelial growth factor expression and microvessel density. A similar Slit2 expression profile was found in human tissue. Importantly, interruption of the Slit2–Robo interaction using R5 inhibited tumor angiogenesis and growth in our in vivo model, which indicates that Slit2‐mediated tumor angiogenesis is a critical process underlying the carcinogenesis of chemical‐induced squamous cell carcinoma. Therefore, targeting Slit–Robo signaling may offer a novel antiangiogenesis approach for oral cancer therapy. (Cancer Sci 2008; 99: 510–517)
The mating game: do opposites really attract?
Authors: GOW JENNIFER L.
Published: February 2008

When selecting a mate, females of many species face a complicated decision: choosing a very closely related mate will lead to inbreeding, while choosing a mate who is too genetically dissimilar risks breaking up beneficial gene complexes or local genetic adaptations. To ensure the best genetic quality of their offspring, the perfect compromise lies somewhere in between: an optimally genetically dissimilar partner. Empirical evidence demonstrating female preference for genetically dissimilar mates is proof of the adage ‘opposites attract’. In stark contrast, Chandler & Zamudio (2008) show in this issue of Molecular Ecology that female spotted salamanders often choose males that are genetically more similar to themselves (although not if the males are small). Along with other recent work, these field studies highlight the broad spectrum of options available to females with respect to relatedness in their choice of mate that belies this rule of thumb.
Fractional exhaled nitric oxide in infants during cow’s milk food challenge
Authors: Gabriele Carmelo , Hol Jeroen , Kerkhof Evelien , Elink Schuurman Beatrix E. E. , Samsom Janneke N. , Hop Wim , Nieuwenhuis Edward E. S. , De Jongste Johan C.
Published: February 2008

Cow’s milk allergy (CMA) is the most common food allergy in early childhood. The golden standard for the diagnosis of CMA is a food challenge after a period of elimination. Increased levels of fractional exhaled nitric oxide (FENO) have been shown after bronchial allergen provocation. We evaluated whether FENO may also be a predictor of a positive reaction during cow’s milk challenge in infants. Forty‐four infants [mean age (range): 4.2 (3.7–4.6) months] suspected of CMA underwent an open food challenge with cow’s milk formula administered in ascending quantities, starting with 2 ml and then 6, 20, 60 and 200 ml until a clinical reaction occurred. Off‐line FENO samples were obtained during tidal breathing by means of a facemask covering infants’ nose and mouth. FENO was measured twice before the challenge (baseline), immediately before each new dose of milk and after a positive reaction or after the last dose of milk. Eleven children showed immediate positive clinical responses to cow’s milk, whereas 13 infants presented only a late‐type reaction. FENO values before or after a positive reaction (either immediate or late) were not different from FENO values at baseline. Baseline FENO in infants with a positive reaction did not differ from FENO in infants without a reaction at any time point. We conclude that FENO values are not predictive and not related to the occurrence of a positive reaction during a cow’s milk challenge in infants, suggesting that a positive reaction may not result from eosinophilic activation.
Two cases of chronic active Epstein–Barr virus infection in which EBV‐specific cytotoxic T lymphocyte was induced after allogeneic bone marrow transplantation
Authors: Miyamura Takako , Chayama Kousuke , Wada Tomoaki , Yamaguchi Kazunari , Yamashita Nobuko , Ishida Toshiaki , Washio Kana , Morishita Naoto , Manki Akira , Oda Megumi , Morishima Tsuneo
Published: February 2008

Abstract:  CAEBV is a high mortality and morbidity disease with life‐threatening complications. Nevertheless, the treatment regimens for CAEBV have not yet been established. Although some reports have described CAEBV therapy involving treatments such as antiviral drugs, immunomodulatory agents, and immunochemotherapy, none of these treatments have been demonstrated to be effective. The only treatment reported to be effective is allogeneic SCT. However, the complications of SCT are severe, so treatment results have been poor. Recently, immunotherapy has been devised, but this is still in the developmental stage. In this report, two cases of CAEBV in which allogeneic SCT was performed soon after diagnosis are reported. In both cases, a high EBV genome titer in the peripheral blood was detected at onset. After SCT, the EBV genome titer decreased as CTL activity gradually increased. This fact suggested that not only high‐dose chemotherapy as a preconditioning treatment of SCT but also increased CTL activity which could eliminate virus‐infected cells might be effective, although additional cases should be studied in order to establish effective treatments.
Does attractiveness in men provide clues to semen quality?
Authors: PETERS M. , RHODES G. , SIMMONS L. W.
Published: February 2008

The psychological mechanisms underlying attractiveness judgements in humans are thought to be evolved adaptations for finding a high quality mate. The phenotype‐linked fertility hypothesis proposes that females obtain reliable information on male fertility from male expression of sexual traits. A previous study of Spanish men reported that facial attractiveness was positively associated with semen quality. We aimed to determine whether this effect was widespread by examining a large sample of Australian men. We also extended our study to determine whether cues to semen quality are provided by components of attractiveness: masculinity, averageness and symmetry. Each male participant was photographed and provided a semen sample that was analyzed for sperm morphology, motility and concentration. Two independent sets of women rated the male photographs for attractiveness, and three further sets of 12 women rated the photographs for masculinity, symmetry or averageness. We found no significant correlations between semen quality parameters and attractiveness or attractive traits. Although male physical attractiveness may signal aspects of mate quality, our results suggest that phenotype‐linked cues to male fertility may not be general across human populations.
Production of methyl mercury in the gut of the Australian termite Mastotermes darwiniensis
Authors: Limper U. , Knopf B. , König H.
Published: February 2008

Animals are often exposed to or can ingest heavy metals along with their food. Therefore, we tested whether the hindgut microbiota of Mastotermes darwiniensis possesses the capability to form methyl mercury. The termite M. darwiniensis (Isoptera) was fed with saw dust containing different concentrations of inorganic mercury. Methyl mercury was determined by purge‐and‐trap capillary gas chromatography‐atom fluorescence spectrometry (CGC‐AFS) using ethyl mercury chloride as the internal standard. Total mercury concentrations were determined in the termite tissue by inductive coupled plasma‐isotope dilution mass spectrometry (ICP‐IDMS) after microwave‐assisted digestion. The obtained results showed in vivo methyl mercury production in terrestrial insects for the first time. Desulfovibrio intestinalis isolated from M. darwiniensis was identified as a biomethylating species of the intestinal microbiota.
INFLUENCE OF NITRIDING ON MICROSTRUCTURE AND FATIGUE BEHAVIOUR OF A SOLUTE‐RICH BETA TITANIUM ALLOY
Authors: Müller C. , Holzwarth U. , Gregory J. K.
Published: February 2008

Abstract— The solute‐rich beta titanium alloy Ti‐3Al‐8V‐6Cr‐4Mo‐4Zr was subjected to 1500 bar nitrogen pressure at elevated temperatures (500–920°C), leading to a diffusion layer with a high surface hardness. Microstructural, crystallographic and compositional analyses indicate that TiN (δ) and Ti2N (ε) are formed at temperatures exceeding 815°C. The increased concentration of nitrogen, which is a potent α‐stabilizer in titanium, also causes α‐Ti to form near the surface. The nitriding treatment does not significantly alter the tensile properties or fatigue limit in solution heat treated material. A subsequent ageing treatment of 72 h at 440°C and 16 h at 500°C reduces toughness significantly, allowing cracks induced by nitriding to propagate more easily into the bulk. Tensile ductility and fatigue performance of aged nitrided Ti‐3Al‐8V‐6Cr—4Mo‐4Zr are thus significantly lower than in the untreated reference condition.
EFFECTS OF DRAWING STRAIN AND BLUING ON THE FATIGUE STRENGTH OF EUTECTOID STEEL WIRES
Authors: Katagiri K. , Sato T. , Shin H. S. , Takahashi L. , Mori H. , Tashiro H. , Sasaki S.
Published: February 2008

Abstract— The effects of bluing, associated with drawing strain, on the fatigue strength of eutectoid steel wires have been investigated. The fatigue limit increases by bluing and the increase is more significant with higher drawing strain. The peak in the fatigue limit with regard to the drawing strain in the wires, at a strain of 2.5, disappears after bluing. On the other hand, in the ferritic steel wires investigated for comparison, the fatigue limit gradually increases with the drawing strain up to 7.7. Furthermore, no appreciable change in the fatigue limit due to bluing is found. Based on the results of hardness tests on fatigue specimens with‐ and without‐bluing, it is deduced that the decrease of the fatigue limit beyond the peak drawing strain in the eutectoid steel wire can partly be attributed to insufficient locking of the high‐density dislocations by solute atoms. The effect of relaxation of residual stress during bluing is also briefly discussed.
FATIGUE CRACK GROWTH BEHAVIOUR OF SM45C STEEL UNDER CYCLIC MODE I WITH SUPERIMPOSED STATIC MODE II LOADINGS
Authors: You B. R. , Lee S. B.
Published: February 2008

Abstract— The practical applications of studies related to constant amplitude mode I loading are somewhat limited, since mode I crack growth is often influenced by mode II (sliding mode) or mode III (tearing mode) in industrial situations. For these cases, criteria, rules, and laws have to be worked out and verified by experiments. However, it is very difficult to evaluate mixed‐mode fatigue cracking due to crack surface interference, crack closure, crack branching, etc. This paper, which defines the length of a branched crack as an effective slant crack with a length equal to the distance between the two crack tips, explains the influences of crack surface interference by introducing concepts of adhesive wear and scrutinizes some related researches on mixed‐mode crack growth behaviour. Additionally an effective stress intensity factor range is described which considers crack closure and crack surface interference and is verified with crack growth tests under mode I fatigue loading and cyclic mode I with a superimposed static mode II loading.
CTOD WITH SLOW STABLE CRACK GROWTH: ANALYSIS OF THE ELASTIC COMPONENT
Authors: Perezipiña J. E.
Published: February 2008

Abstract— The errors made during calculations for the “elastic” component of CTOD, δe, under slow stable crack growth conditions are analyzed and a model that considers this situation is proposed. Some examples are shown in which important errors occur in the CTOD value as a consequence of not having considered slow stable crack growth. This analysis complements previous work where an adaptation of the Plastic Hinge Model was made in order to consider corrections in the plastic component of CTOD due to rotation and stable crack growth.

The errors in Schwalbe's CTOD term, δ5, which relate to a lack of alignment to the average crack front are also studied. Since the absolute value of this inexactitude is not known, bounds are set to this error.
Pathological features of Gleason score 6 prostate cancers in the low and intermediate range of prostate‐specific antigen level: is there a difference?
Authors: Pelzer Alexandre E. , Colleselli Daniela , Bektic Jasmin , Steiner Eberhard , Ramoner Reinhold , Mitterberger Michael , Schwentner Christian , Schaefer Georg , Ongarello Stefano , Bartsch Georg , Horninger Wolfgang
Published: February 2008

OBJECTIVE

To assess the pathological features of Gleason score 6 prostate cancers after radical prostatectomy in the low (<4 ng/mL) and intermediate range of prostate‐specific antigen level (4–10 ng/mL), as such prostate cancers are considered to be well differentiated tumours with a low risk for recurrence after therapy.

PATIENTS AND METHODS

In all, 1354 patients with T1c prostate cancer and PSA levels of <10.0 ng/mL had a radical retropubic prostatectomy. Patients with Gleason score 6 tumours were divided into two groups, those with PSA levels of <4 and 4.0–10.0 ng/mL. Extracapsular extension, positive surgical margins, biochemical recurrence (BCR) and mean time to BCR were evaluated.

RESULTS

Of the 1354 patients, there were 437 (32.3%) with Gleason score 6 prostate cancers. Patients in the low PSA group had less extraprostatic disease than those with a higher level (5.9% vs 14.5%) and both groups had an almost equal proportion of positive surgical margins (9.4% vs 11.0%). In the low PSA group there was statistically significantly shorter BCR than in the high PSA group, with a mean time to BCR of 1.7 vs 3.1 years.

CONCLUSIONS

These results show a statistically significantly higher rate of extraprostatic disease and earlier BCR in men with a high than a low PSA level even in Gleason score 6 prostate cancer. As the rate of BCR and extracapsular extension are significantly related to prostate cancer mortality, these findings further support the concept of screening using low PSA levels.
Zones of ambiguity and identity politics in Samoa
Authors: Mageo Jeannette
Published: February 2008

Here I illustrate a deconstructive practice through which indigenes actively resist colonial identity politics. By creating ‘zones of ambiguity’ in the performing arts, indigenes think through colonial images of gender and race. Bhabha's ‘zones of ambivalence’ characterize contradictions in colonists’ approach to the colonized and self‐contradictory identities that colonists force ‘mimic men’ to assume. Zones of ambiguity, in contrast, characterize indigenes’ approach to the hybrid identities that colonists’ ambivalence visits upon them: indigenes purposefully design these zones to transform stereotypic projections and to comment on colonial experience. I explore these ideas through two evening performances in Samoa described in two 1930s travelogues that allude to key figures in Samoan (post)colonial history – the ceremonial virgin (tāupōu) and the male transvestite (fa’afafine).

L’auteur illustre ici une pratique déconstructive par laquelle les autochtones résistent activement aux politiques identitaires coloniales. En créant des « zones d’ambiguïté» dans les arts du spectacle, les autochtones détournent les images coloniales du genre et de la race. Les « zones d’ambivalence » de Bhabha caractérisent les contradictions dans l’approche par le colonisateur des colonisés et les identités entrant en contradiction avec elles‐mêmes qu’il impose aux « mimic men ». En revanche, les zones d’ambiguïté caractérisent l’approche par les autochtones des identités hybrides que l’ambivalence des colons leur renvoie : ils conçoivent délibérément ces zones de manière à transformer les projections stéréotypées et à commenter l’expérience coloniale. L’auteur explore ces idées par l’intermédiaire de deux spectacles donnés en soirée aux Samoa, décrites par des voyageurs‐conférenciers dans les années 1930 et faisant référence à des personnages clés de l’histoire (post)coloniale des Samoa : la vierge cérémonielle (tāupōu) et le travesti masculin (fa’afafine).
The English negative comparative particle1
Authors: Laker Stephen
Published: February 2008

The most common dialectal alternative to the Modern English comparative particle than is a negative form with variants such as ne, na, and nor, e.g. You’re my son – more to me nor any son (Dickens, Great Expectationsii. xx). This paper presents a detailed historical survey of this dialectal usage in varieties of British and Irish English, and offers an assessment of its regional distribution since the medieval period. The paper also investigates the possible origins of the form, first highlighting some problems of previous analyses, before comparing and contrasting the use of negation in comparative constructions in French and Insular Celtic. The evidence strongly suggests that the negative comparative particle in English should be seen as an areal feature of the British Isles, and that language contact with Celtic lies at the root of it.
Social network analysis and the eighteenth‐century family network: a case study of the Walpole family
Authors: Henstra Froukje
Published: February 2008

In this paper1 I demonstrate that the present‐day research model of social network analysis can successfully be used to describe and explain linguistic variation and change in a historical context. I do so by presenting a case study of the language of the Walpole family in relation to the norm as set in contemporary eighteenth‐century grammars. I select three linguistic features which were commented on by Lowth and test these against the corpus of the letters of Walpole family members, which I have created from the complete edition of Horace Walpole’s correspondence.
Contribution to the study of a euphemism in the intimate lexis of Slavonic and Germanic languages1
Authors: Cooper Brian
Published: February 2008

This paper studies the metaphorical origin of a well‐known vulgar euphemistic name for the penis, especially in Germanic (e.g. English cock and German Hahn) and Slavonic (e.g. words with the stems pet‐/pit‐, kur‐ and kog‐/koh‐/kok‐), but also in some other languages. Although it can be surmised that the vulgar sense of these words in some languages may have arisen from the sense ‘(stop)cock’, in view of the urinary function of the penis, this view seems inaccurate not only in the Slavonic but also in the Germanic languages. Judging by the material presented, it is much more probable that the reasons underlying the metaphor Hahn/cock/petux‘rooster’ > Hahn/cock/petux‘penis’ are linked first and foremost with the ancient association of the rooster with male characteristics, primarily of the procreative type. It is from this metaphor that the sense Hahn/cock/petux‘spigot’ arises (the penis is envisaged as a tap). It is possible that this same metaphor gave rise to the concept Hahn/cock/kurok‘hammer of a firearm’ (the cocking piece and the penis can stick up like the neck and head of a crowing cock).
Misconvergence to the stimulus plane causes apparent displacement of the stimulus elements seen monocularly1
Authors: NAKAMIZO SACHIO , KAWABATA HIDEAKI , ONO HIROSHI
Published: February 2008

Abstract:  When one binocularly views a group of vertical lines through a ring, the outermost line segments (one on each side) seen within the ring are seen monocularly while the segments of the same lines outside the ring are seen binocularly. The monocular segments appear to be displaced outward with respect to the center of the ring and with respect to the corresponding binocular segments outside the ring. Three experiments examined the extent and direction of this illusory displacement as a function of viewing distance, fixation disparity created by varying the angles of the two arms of a haploscope, and fixation disparity created by a stereoscope and different Nonius stimuli. The results of the experiments confirmed the hypothesis that the apparent displacement is due to misconvergence in accordance with Wells‐Hering's laws of visual direction.
The “Strong Programme”, Normativity, and Social Causes
Authors: CALVERT‐MINOR CHRIS
Published: February 2008

Barry Barnes and David Bloor of the Strong Programme of the sociology of knowledge advance a naturalized epistemology that reduces all accounts of normativity to social causes. I endorse their program of naturalizing one kind of normativity, but I argue that there is another kind they cannot naturalize. Within the context of sociological explanations of rationality, there are (1) norms of rationality instantiated by scientists that Barnes and Bloor study, and (2) Barnes and Bloor's own normative ascriptions of scientists as rational beings. I argue that Barnes and Bloor successfully justify their naturalization of the norms of rationality of the scientists they describe by a methodological caution and arguments from under‐determination and finitism. But they inevitably fail to naturalize their own normative ascriptions of those scientists as rational.
The MTHFD1 Gene is not Involved in Cleft Lip with or Without Palate Onset Among the Italian Population
Authors: Palmieri A. , Masiero E. , Martinelli M. , Scapoli L. , Pezzetti F. , Caramelli E. , Guidotti L. , Carinci F.
Published: February 2008

Nonsyndromic cleft lip with or without cleft palate (CL/P) is the most common orofacial malformation, having a non‐Mendelian and multifactorial aetiology. It has been shown that polymorphic variants of genes encoding key proteins of folate and methionine metabolism might be important maternal risk factors for having a child with these craniofacial anomalies. The aim of this study was to evaluate the role of two polymorphisms of the methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) gene, the A1958G and the G401A variants, on the risk of CL/P in the Italian population.

A1958G and G401A polymorphism genotyping of MTHFD1 was performed on 216 CL/P triads, (patient and parents), for this study by restriction endonuclease digestion of PCR products. Linkage disequilibrium between markers and disease was tested using both pairwise and haplotype analyses. In our case‐parents triad design no significant association between MTHFD1 and the disease is evident. Our data do not support MTHFD1 involvement in CL/P onset among the Italian population.
NUCLEOMORPH KARYOTYPE DIVERSITY IN THE FRESHWATER CRYPTOPHYTE GENUS CRYPTOMONAS1
Authors: Phipps Kyle D. , Donaher Natalie A. , Lane Christopher E. , Archibald John M.
Published: February 2008

Cryptophytes are unicellular, biflagellate algae with plastids (chloroplasts) derived from the uptake of a red algal endosymbiont. These organisms are unusual in that the nucleus of the engulfed red alga persists in a highly reduced form called a nucleomorph. Nucleomorph genomes are remarkable in their small size (<1,000 kilobase pairs [kbp]) and high degree of compaction (∼1 kbp per gene). Here, we investigated the molecular and karyotypic diversity of nucleomorph genomes in members of the genus Cryptomonas. 18S rDNA genes were amplified, sequenced, and analyzed from C. tetrapyrenoidosa Skuja CCAP979/63, C. erosa Ehrenb. emmend. Hoef‐Emden CCAP979/67, Cryptomonas sp. CCAP979/52, C. lundii Hoef‐Emden et Melkonian CCAP979/69, and C. lucens Skuja CCAP979/35 in the context of a large set of publicly available nucleomorph 18S rDNA sequences. Pulsed‐field gel electrophoresis (PFGE) was used to examine the nucleomorph genome karyotype of each of these strains. Individual chromosomes ranged from ∼160 to 280 kbp in size, with total genome sizes estimated to be ∼600–655 kbp. Unexpectedly, the nucleomorph karyotype of Cryptomonas sp. CCAP979/52 is significantly different from that of C. tetrapyrenoidosa and C. lucens, despite the fact that their 18S rDNA genes are >99% identical to one another. These results suggest that nucleomorph karyotype similarity is not a reliable indicator of evolutionary affinity and provides a starting point for further investigation of the fine‐scale dynamics of nucleomorph genome evolution within members of the genus Cryptomonas.
DETECTING EVOLUTIONARY TRANSFER OF GENES USING PhIGs1
Authors: Boore Jeffrey L.
Published: February 2008

Organisms have acquired plastids by convoluted paths that have provided multiple opportunities for gene transfer into a host nucleus from intracellular organisms, including the cyanobacterial ancestor of plastids, the proteobacterial ancestor of mitochondria, and both green and red algae whose engulfment has led to secondary acquisition of plastids. These gene movements are most accurately demonstrated by building phylogenetic trees that identify the evolutionary origin of each gene, and one effective tool for this is “PhIGs” (Phylogenetically Inferred Groups; http://PhIGs.org), a set of databases and computer tools with a Web interface for whole‐genome evolutionary analysis. PhIGs takes as input gene sets of completely sequenced genomes, builds clusters of genes using a novel, graph‐based approach, and reconstructs the evolutionary relationships among all gene families. The user can view and download the sequence alignments, compare intron‐exon structures, and follow links to functional genomic databases. Currently, PhIGs contains 652,756 genes from 45 genomes grouped into 61,059 gene families. Graphical displays show the relative positions of these genes among genomes. PhIGs has been used to detect the evolutionary transfer of hundreds of genes from cyanobacteria and red algae into oömycete nuclear genomes, revealing that even though they have no plastids, their ancestors did, having secondarily acquired them from an intracellular red alga. A great number of genomes are soon to become available that are relevant to our broader understanding of the movement of genes among intracellular compartments after engulfing other organisms, and PhIGs will be an effective tool to interpret these gene movements.
Effects of 6 Months of Aging in Water on Hardness and Surface Roughness of Two Microhybrid Dental Composites
Authors: De Moraes Rafael Ratto , Marimon José Laurindo Machado , Jochims Schneider Luis Felipe , Sinhoreti Mário Alexandre Coelho , Correr‐Sobrinho Lourenço , Bueno Márcia
Published: February 2008

Purpose: This study assessed the effect of 6 months of aging in water on surface roughness and surface/subsurface hardness of two microhybrid resin composites.

Materials and Methods: Filtek Z250 and Charisma were tested. Cylindrical specimens were obtained and stored in distilled water for 24 hours or 6 months, at 37°C. For Knoop hardness evaluation, the specimens were transversely wet‐flattened, and indentations were made on surface and subsurface layers. Data were submitted to three‐way ANOVA and Tukey's test (α≤ 0.05). Surface roughness baseline measurements were made at 24 hours and repeated after 6 months of storage. Data were submitted to repeated measures ANOVA and Tukey's test (α≤ 0.05).

Results: Surface hardness (KHN, kg/mm2) means (± standard deviation) ranged from 55 ± 1 to 49 ± 4 for Z250 and from 50 ± 2 to 41 ± 3 for Charisma, at 24 hours and 6 months, respectively. Subsurface means ranged from 58 ± 2 to 61 ± 3 for Z250 and from 50 ± 1 to 54 ± 2 for Charisma, at 24 hours and 6 months. For both composites, the aged specimens presented significantly softer surfaces (p < 0.01). For the subsurface hardness, alteration after storage was detected only for Charisma, which presented a significant rise in hardness (p < 0.01). Z250 presented significantly harder surface and subsurface layers in comparison with Charisma. Surface roughness (Ra, μm) means ranged from 0.07 ± 0.00 to 0.07 ± 0.01 for Z250 and from 0.06 ± 0.01 to 0.07 ± 0.01 for Charisma, at 24 hours and 6 months, respectively. For both composites, no significant roughness alteration was detected during the study (p= 0.386).

Conclusions: The 6‐month period of storage in water presented a significant softening effect on the surfaces of the composites, although no significant deleterious alteration was detected for the subsurface hardness. In addition, the storage period had no significant effect on the surface roughness of the materials.
A Double‐Point Mutation in the Selectivity Filter Site of the KCNQ1 Potassium Channel Results in a Severe Phenotype, LQT1, of Long QT Syndrome
Authors: IKRAR TARUNA , HANAWA HARUO , WATANABE HIROSHI , OKADA SHINSUKE , AIZAWA YOSHIYASU , RAMADAN MAHMOUD M. , KOMURA SATORU , YAMASHITA FUMIO , CHINUSHI MASAOMI , AIZAWA YOSHIFUSA
Published: February 2008

Introduction: Slowly activating delayed‐rectifier potassium currents in the heart are produced by a complex protein with α and β subunits composed of the potassium voltage‐gated channel KQT‐like subfamily, member 1 (KCNQ1) and the potassium voltage‐gated channel Isk‐related family, member 1 (KCNE1), respectively. Mutations in KCNQ1 underlie the most common type of hereditary long QT syndrome (LQTS). Like other potassium channels, KCNQ1 has six transmembrane domains and a highly conserved potassium selectivity filter in the pore helix called “the signature sequence.” We aimed to investigate the functional consequences of a newly identified mutation within the signature sequence.

Methods and Results: Potassium channel genomic DNA from a family with clinical evidence of LQTS was amplified by polymerase chain reaction (PCR), and the resulting products were then sequenced. Three family members had a double‐point mutation in KCNQ1 at nucleotides 938 (T‐to‐A) and 939 (C‐to‐A), resulting in an isoleucine‐to‐lysine change at amino acid position 313. These patients displayed prolonged QTc intervals (629, 508, and 500 ms1/2, respectively) and repetitive episodes of syncope, but no deafness. Three‐dimensional structure modeling of KCNQ1 revealed that this mutation is located at the center of the channel pore. COS‐7 cells displayed a lack of current when transfected with a plasmid expressing the mutant. In addition, the mutant displayed a dominant negative effect on current but appeared normal with respect to plasma membrane integration.

Conclusion: An I313K mutation within the selectivity filter of KCNQ1 results in a dominant‐negative loss of channel function, leading to a long QT interval and subsequent syncope.
A primer for the prescription of short‐daily and nocturnal hemodialysis
Authors: BENAROIA Mark , PIERRATOS Andreas , NESRALLAH Gihad E.
Published: February 2008

More frequent and intensive hemodialysis (HD) schedules continue to garner interest internationally. Two dominant regimens have emerged, namely short‐daily and nocturnal HD. A growing body of observational data suggests that these regimens allow more rigorous control of biochemical and physical parameters when compared with conventional HD. This review describes the methodology used in providing more frequent or sustained HD both in center and at home, and attempts to provide a physiological rationale for the practices described in the current literature.
Applications of SELDI‐MS technology in oncology
Authors: Whelan L. C. , Power K. A. R. , McDowell D. T. , Kennedy J. , Gallagher W. M.
Published: February 2008

Introduction

Surface enhanced laser desorption/ionisation‐mass spectrometry

Sampling

Clinical applications

In vitro applications

Protein interactions

Advantages over conventional technologies

Limitations

Conclusions

Considerable interest, speculation and controversy have been generated utilising surface‐enhanced laser desorption/ionization in conjunction with mass spectrometry (SELDI‐MS) for the diagnosis, prognosis and therapeutic monitoring of cancer and offers an attractive approach to cancer biomarker discovery from tissues and biological fluids. This technology utilises a combination of mass spectrometry and chromatography to facilitate protein profiling of complex biological mixtures. Compared to some other more traditional proteomic platforms, such as 2D polyacrylamide gel electrophoresis, it has a high‐throughput capability and can resolve low‐mass proteins. However, a considerable number of challenging issues related to the design of studies, including reproducibility, sensitivity, specificity, variation in sample collection, processing and storage, have been reported as problematic with this technology; albeit some of these concerns could perhaps also be lauded against other proteomic approaches that have attempted to address complex protein mixtures, such as plasma. Applications, successes and limitations of SELDI‐MS in both clinical and basic science arenas will be reviewed in this article.
Genetic variation in the serotonin transporter modulates neural system‐wide response to fearful faces
Authors: Surguladze S. A. , Elkin A. , Ecker C. , Kalidindi S. , Corsico A. , Giampietro V. , Lawrence N. , Deeley Q. , Murphy D. G. M. , Kucharska‐Pietura K. , Russell T. A. , McGuffin P. , Murray R. , Phillips M. L.
Published: February 2008

A distributed, serotonergically innervated neural system comprising extrastriate cortex, amygdala and ventral prefrontal cortex is critical for identification of socially relevant emotive stimuli. The extent to which a genetic variation of serotonin transporter gene 5‐HTTLPR impacts functional connectivity between the amygdala and the other components of this neural system remains little examined. In our study, neural activity was measured using event‐related functional magnetic resonance imaging in 29 right‐handed, white Caucasian healthy subjects as they viewed mild or prototypical fearful and neutral facial expressions. 5‐HTTLPR genotype was classified as homozygous for the short allele (S/S), homozygous for the long allele (L/L) or heterozygous (S/L). S/S showed greater activity than L/L within right fusiform gyrus (FG) to prototypically fearful faces. To these fearful faces, S/S more than other genotype subgroups showed significantly greater positive functional connectivity between right amygdala and FG and between right FG and right ventrolateral prefrontal cortex (VLPFC). There was a positive association between measure of psychoticism and degree of functional connectivity between right FG and right VLPFC in response to prototypically fearful faces. Our data are the first to show that genotypic variation in 5‐HTTLPR modulates both the amplitude within and the functional connectivity between different components of the visual object‐processing neural system to emotionally salient stimuli. These effects may underlie the vulnerability to mood and anxiety disorders potentially triggered by socially salient, emotional cues in individuals with the S allele of 5‐HTTLPR.
Allosteric modulation of Euphorbia peroxidase by nickel ions
Authors: Pintus Francesca , Mura Anna , Bellelli Andrea , Arcovito Alessandro , Spanò Delia , Pintus Anna , Floris Giovanni , Medda Rosaria
Published: February 2008

A class III peroxidase, isolated and characterized from the latex of the perennial Mediterranean shrub Euphorbia characias, contains one ferric iron–protoporphyrin IX pentacoordinated with a histidine ‘proximal’ ligand as heme prosthetic group. In addition, the purified peroxidase contained 1 mole of endogenous Ca2+ per mole of enzyme, and in the presence of excess Ca2+, the catalytic efficiency was enhanced by three orders of magnitude. The incubation of the native enzyme with Ni2+ causes reversible inhibition, whereas, in the presence of excess Ca2+, Ni2+ leads to an increase of the catalytic activity of Euphorbia peroxidase. UV/visible absorption spectra show that the heme iron remains in a quantum mechanically mixed‐spin state as in the native enzyme after addition of Ni2+, and only minor changes in the secondary or tertiary structure of the protein could be detected by fluorescence or CD measurements in the presence of Ni2+. In the presence of H2O2 and in the absence of a reducing agent, Ni2+ decreases the catalase‐like activity of Euphorbia peroxidase and accelerates another pathway in which the inactive stable species accumulates with a shoulder at 619 nm. Analysis of the kinetic measurements suggests that Ni2+ affects the H2O2‐binding site and inhibits the formation of compound I. In the presence of excess Ca2+, Ni2+ accelerates the reduction of compound I to the native enzyme. The reported results are compatible with the hypothesis that ELP has two Ni2+‐binding sites with opposite functional effects.
Thermodynamics of the β2 association in light‐harvesting complex I of Rhodospirillum rubrum
Authors: Seguin Jérôme , Mayer Claudine , Robert Bruno , Arluison Véronique
Published: February 2008

The core light‐harvesting LH1 protein from Rhodospirillum rubrum can dissociate reversibly in the presence of n‐octyl‐β‐d‐glucopyranoside into smaller subunit forms, exhibiting a dramatic blue‐shift in absorption. During this process, two main species are observed: a dimer that absorbs at 820 nm (B820) and a monomer absorbing at 777 nm (B777). In the presence of n‐octyl‐β‐D‐glucopyranoside, we have previously shown that the B820 form is not only constituted by the αβ heterodimer alone, but that it exists in an equilibrium between the αβ heterodimer and β2 homodimer states. We investigated the dissociation equilibrium for both oligomeric B820 forms. Using a theoritical model for αβ and β2, we conclude that the B820 homodimer is stabilized by both hydrophobic effects (entropy) and non‐covalent bonds (enthalpy). We discuss a possible interpretation of the energy changes.