bluuebunny/crossref_metadata_2025 huggingface dataset:
Crop responses to temperature and precipitation according to long-term multi-location trials at high-latitude conditions
Authors: PELTONEN-SAINIO P. , JAUHIAINEN L. , HAKALA K.
Published: November 2010

Global warming has accelerated in recent decades and the years 1995–2006 were the warmest ever recorded. Also, in Finland, the last decade has been exceptionally warm. Hence, this study examines how current field crop cultivars, adapted to northern long-day conditions and short growing seasons, have responded to the elevated temperatures, especially with regard to determination of yield potential and quality. These comparisons were carried out with spring and winter wheat (Triticum aestivum L.), oats (Avena sativa L.), barley (Hordeum vulgare L.), winter rye (Secale cereale L.), pea (Pisum sativum L.) and rapeseed (turnip rape, Brassica rapa L. and oilseed rape, B. napus L.). Long-term data sets of MTT Official Variety Trials and the Finnish Meteorological Institute were used to study crop responses to precipitation and elevated temperatures at different growth phases. The MTT data sets were also grouped into experiments that could be considered typical of the temperature conditions in the period 1971–2000 seasons (termed ‘1985’ conditions) or typical of the period 2010–39 (termed ‘2025’). At elevated temperatures, yields generally declined in these relatively cool growing conditions of northern Europe, except for pea. Elevated temperatures tended to have negative effects both in the pre- and post-anthesis phases, but the response depended on species. The response was probably associated with reduced water availability, which limited yield determination, especially in early growth phases. For example, in spring cereals a decrease in early summer precipitation by 10 mm decreased yields by 45–75 kg/ha. As warmer conditions also typically hastened development and growth in such generally cool growing conditions of Finland, it is essential that breeding programmes produce cultivars that are less sensitive to elevated temperatures, which are likely to become more frequent in future.
Revision of the Cancellariidae (Gastropoda: Caenogastropoda) in the deep water of the Norwegian Sea, with the description of a new species ofAdmete
Authors: Høisæter Tore
Published: November 2010

A new species ofAdmeteMøller, 1842 (Cancellariidae),A. clivicolais described from the upper continental slope off south-western Norway, and the speciesAdmete contabulataFriele, 1879 is reinstated as a valid species.Iphinopsis inflata(Friele, 1879) is redescribed and a lectotype for the species is established. The taxonomic status and bathymetric distribution of the species ofAdmeteandIphinopsisin the Norwegian Sea are discussed.
Endeolophos skeneaesp. nov. (Chromadoridae)—a free-living marine nematode epibiotically associated with deep-sea gastropodSkenea profunda(Skeneidae)
Authors: Holovachov Oleksandr , Boström Sven , Reid Nicole , Warén Anders , Schander Christoffer
Published: November 2010

A new species,Endeolophus skeneaesp. nov., epibiotically associated with the gastropodSkenea profunda, is described from light microscope and scanning electron microscope observations. The new species is characterized by homogeneous ornamentation of the cuticle with annules with very fine and numerous longitudinal ridges, equally distributed around the body, subcuticular discontinuity in cuticle pattern along the lateral sectors of the body, relatively long body (1.1–1.6 mm) and relatively long tail (141–188 μm, c' = 7.5–11.4), short (19–22 μm) L-shaped spicules with ventrally bent blade and simple plate-like gubernaculum without apophysis. Symbiotic associations between aquatic nematodes and molluscs are discussed, with special emphasis onDreissena polymorpha, zebra mussels. It is suggested that nematodes find food and shelter in the mantle cavity of the bivalve molluscs, and in the umbilicus and aperture of the gastropods, but to reveal the exact mechanisms of symbiotic associations of nematodes with aquatic molluscs requires further research.
Energy sensing by the AMP-activated protein kinase and its effects on muscle metabolism
Authors: Hardie D. Grahame
Published: November 2010

The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status, and a regulator of energy balance at both the cellular and whole body levels. Although ubiquitously expressed, its function is best understood in skeletal muscle. AMPK contains sites that reversibly bind AMP or ATP, with an increase in cellular AMP:ATP ratio (signalling a fall in cellular energy status) switching on the kinase. In muscle, AMPK activation is therefore triggered by sustained contraction, and appears to be particularly important in the metabolic changes that occur in the transition from resistance to endurance exercise. Once activated, AMPK switches on catabolic processes that generate ATP, while switching off energy-requiring processes not essential in the short term. Thus, it acutely activates glucose uptake (by promoting translocation of the transporter GLUT4 to the membrane) and fatty acid oxidation, while switching off glycogen synthesis and protein synthesis (the later via inactivation of the mammalian target-of-rapamycin pathway). Prolonged AMPK activation also causes some of the chronic adaptations to endurance exercise, such as increased GLUT4 expression and mitochondrial biogenesis. AMPK contains a glycogen-binding domain that causes a sub-fraction to bind to the surface of the glycogen particle, and it can inhibit glycogen synthesis by phosphorylating glycogen synthase. We have shown that AMPK is inhibited by exposed non-reducing ends in glycogen. We are working on the hypothesis that this ensures that glycogen synthesis is rapidly activated when glycogen becomes depleted after exercise, but is switched off again as soon as glycogen stores are replenished.
Epigenetic modifications and human pathologies: cancer and CVD
Authors: Duthie Susan J.
Published: November 2010

Epigenetic changes are inherited alterations in DNA that affect gene expression and function without altering the DNA sequence. DNA methylation is one epigenetic process implicated in human disease that is influenced by diet. DNA methylation involves addition of a 1-C moiety to cytosine groups in DNA. Methylated genes are not transcribed or are transcribed at a reduced rate. Global under-methylation (hypomethylation) and site-specific over-methylation (hypermethylation) are common features of human tumours. DNA hypomethylation, leading to increased expression of specific proto-oncogenes (e.g. genes involved in proliferation or metastasis) can increase the risk of cancer as can hypermethylation and reduced expression of tumour suppressor (TS) genes (e.g. DNA repair genes). DNA methyltransferases (DNMT), together with the methyl donor S-adenosylmethionine (SAM), facilitate DNA methylation. Abnormal DNA methylation is implicated not only in the development of human cancer but also in CVD. Polyphenols, a group of phytochemicals consumed in significant amounts in the human diet, effect risk of cancer. Flavonoids from tea, soft fruits and soya are potent inhibitors of DNMT in vitro, capable of reversing hypermethylation and reactivating TS genes. Folates, a group of water-soluble B vitamins found in high concentration in green leafy vegetables, regulate DNA methylation through their ability to generate SAM. People who habitually consume the lowest level of folate or with the lowest blood folate concentrations have a significantly increased risk of developing several cancers and CVD. This review describes how flavonoids and folates in the human diet alter DNA methylation and may modify the risk of human colon cancer and CVD.
How can the multi-disciplinary team meet the psychological needs of adolescents with cancer? A review of the literature
Authors: Singh Kam , Hodgson Denyse
Published: November 2010

A cancer diagnosis is likely to have a devastating effect when it occurs, but it is possibly especially problematic during adolescence. The many challenges faced by adolescents have led to a concern for their psychosocial well-being. There is evidence to support the notion that the provision of effective psychosocial care improves the outcomes of patients with cancer. The review of the literature has identified that amongst the psychological challenges; there is uncertainty and fear around the status and progression of the cancer. Issues such as body image and sexuality and fertility have been highlighted as a major cause of concern for adolescents. The literature suggests health professionals need to be trained in such areas to give the appropriate care and support. It has also been identified that hopefulness and a positive attitude by patients, families and the multi disciplinary team contribute to positive outcomes. Nurses play a key role in providing psychosocial care as they are primarily the ones who deliver the daily care and can be used as a mediator between the multi disciplinary team. Other disciplines such as Clinical Nurse Specialists, Activities Coordinators, Social workers and Psychotherapists all contribute to the overall direction and experience of care.
Radiation-induced toxicity in cancer patients with low plasma fibronectin levels
Authors: Baluna Roxana G. , Fuller Clifton D. , Eng Tony Y. , Ampil Federico L. , Thomas Charles R.
Published: November 2010

The present study was carried out to evaluate the levels of plasma fibronectin (Fn) in cancer patients undergoing radiation therapy (RT) in correlation with outcomes in terms of radiation toxicity. A total of 26 patients with lung and gastrointestinal (GI) cancer, treated with RT were enrolled in this study. Plasma Fn levels were determined before and following a course of RT. The Radiation Therapy Oncology Group (RTOG) criteria were used to determine the grade of RT toxicity. Statistical analysis utilised the nonparametric Mann–WhitneyU-test as well as bivariate linear regression. Pre-RT Fn levels were significantly higher in cancer patients without toxicity (median ± SE) (485.0 ± 87 μg/ml) as compared with the levels of plasma Fn in patients with grade I–II RTOG acute toxicity (354.0 ± 74 μg/ml,p= 0.01). No significant difference in Fn levels was found in patients with grade I toxicity compared with patients with grade II toxicity. In addition, low baseline Fn levels (148 and 299 μg/ml) were observed in two lung cancer patients who developed symptomatic pneumonitis during the first 2 months after RT. These preliminary results suggest that low baseline Fn may have potential as a predictive marker for development of RT-induced toxicity.
Collective reparation for victims of armed conflict
Authors: Rosenfeld Friedrich
Published: November 2010

Reparations are essential to establishing justice after armed conflicts. The question whether international law endorses an individual right to reparation has been a focal point of recent discussion in that regard. The victims of armed conflicts are, however, not only individuals but also collectives. The present article therefore examines the issue of collective reparation. While it is submitted that the question whether there is a right to such a remedy is not yet settled, it is argued that responsible parties should develop robust programmes of collective reparation.
Global Standards for Sovereign Wealth Funds: The Quest for Transparency
Authors: DE BELLIS Maurizia
Published: November 2010

Sovereign Wealth Funds (SWFs) are currently under increased scrutiny. This article aims at identifying the features and likely impact of the Generally Accepted Principles and Practices (GAPP), using two lenses, both well known to legal scholars, especially within global administrative law (GAL) studies: global standards and transparency. On the one hand, contrasting the GAPP with other types of global financial standards can help identify the most powerful incentives to foster compliance. On the other hand, even though the transparency provisions requesting SWFs to provide public information concerning their legal basis, structure, and financing decisions appear to be a step in the right direction, they need further clarification so that a proper balance between disclosure and the need to avoid unnecessary costs can be struck. Moreover, this article claims that the effectiveness of disclosure provisions in fostering the accountability of the funds depends also on the existence of structural elements.
Chinese Philosophy and International Law
Authors: PAN Junwu
Published: November 2010

As a growing power, China is confronted with many challenges that include the revision of its erstwhile philosophies so as to better adapt itself to globalization and the contemporary international legal order. This article analyzes the close relationship between China’s attitude to international law and Chinese philosophy. It aims to help people to understand China’s behaviour on the global plane and the steps China is taking to integrate more seamlessly into the international legal order.
Iron snow zones as a mechanism for generating Mercury's weak observed magnetic field
Authors: Vilim R. , Stanley S. , Hauck S. A.
Published: November 2010

The anomalously weak observed magnetic field of Mercury is difficult to explain by appealing to crustal remanent magnetism or Earth‐like dynamo mechanisms. Although the field is likely caused by a hydromagnetic dynamo, the field strength is far weaker than the characteristic strength expected from an active, strong field dynamo. Recent experimental work has shown that sources of compositional convection exist in mixtures of sulfur and iron at temperatures and pressures relevant to Mercury's core. The number and location of these iron “snow” zones is dependent on the sulfur content of the liquid portion of the core. We use a numerical dynamo model to show that the core states which include a snow zone midway through the core produce the observed field strength and expected field partitioning of the Mercurian magnetic field.
Enhanced nutrient supply to the California Current Ecosystem with global warming and increased stratification in an earth system model
Authors: Rykaczewski Ryan R. , Dunne John P.
Published: November 2010

A leading hypothesis relating productivity with climate variability in the California Current Ecosystem (CCE) describes an alternation between warmer, well‐stratified periods of low productivity and cooler periods of high productivity. This empirical relationship suggests that productivity will decline with global warming. Here, we explore the response of productivity to future climate change in the CCE using an earth system model. This model projects increases in nitrate supply and productivity in the CCE during the 21st century despite increases in stratification and limited change in wind‐driven upwelling. We attribute the increased nitrate supply to enrichment of deep source waters entering the CCE resulting from decreased ventilation of the North Pacific. Decreases in dissolved‐oxygen concentration and increasing acidification accompany projected increases in nitrate. This analysis illustrates that anthropogenic climate change may be unlike past variability; empirical relationships based on historical observations may be inappropriate for projecting ecosystem responses to future climate change.
Features of separatrix regions in magnetic reconnection: Comparison of 2‐D particle‐in‐cell simulations and Cluster observations
Authors: Lu Quanming , Huang Can , Xie Jinlin , Wang Rongsheng , Wu Mingyu , Vaivads Andris , Wang Shui
Published: November 2010

In collisionless magnetic reconnection, the in‐plane Hall currents are carried mainly by the magnetized electrons. The in‐plane Hall currents are directed toward the X line along the magnetic field lines just inside the separatrices and away from the X line along the separatrices. Such a current system leads to the quadrupole out‐of‐plane magnetic field with the peaks between the regions carrying the in‐plane currents. Simultaneously, the electron flow toward the X line along the separatrices causes electron density depletions along the separatrices. In this paper, the features of separatrix regions in magnetic reconnection and the relations between the electron density depletions and the out‐of‐plane magnetic field are investigated with both two‐dimensional particle‐in‐cell simulations and Cluster observations. We conclude that the electron density depletions are formed because of the magnetic mirror, and they are outside the peaks of the out‐of‐plane magnetic field. Such a theoretical prediction is confirmed by both simulations and observations.
Scaling of plate tectonic convection with pseudoplastic rheology
Authors: Korenaga Jun
Published: November 2010

The scaling of plate tectonic convection is investigated by simulating thermal convection with pseudoplastic rheology and strongly temperature‐dependent viscosity. The effect of mantle melting is also explored with additional depth‐dependent viscosity. Heat flow scaling can be constructed with only two parameters, the internal Rayleigh number and the lithospheric viscosity contrast, the latter of which is determined entirely by rheological properties. The critical viscosity contrast for the transition between plate tectonic and stagnant lid convection is found to be proportional to the square root of the internal Rayleigh number. The relation between mantle temperature and surface heat flux on Earth is discussed on the basis of these scaling laws, and the inverse relationship between them, as previously suggested from the consideration of global energy balance, is confirmed by this fully dynamic approach. In the presence of surface water to reduce the effective friction coefficient, the operation of plate tectonics is suggested to be plausible throughout the Earth history.
Integration of the GG model with SEBAL to produce time series of evapotranspiration of high spatial resolution at watershed scales
Authors: Long Di , Singh Vijay P.
Published: November 2010

Lack of good quality satellite images because of cloud contamination or long revisit time severely degrades predictions of evapotranspiration (ET) time series at watershed/regional scales from satellite‐based surface flux models. We integrate the feedback model developed by Granger and Gray (the GG model) with the Surface Energy Balance Algorithm for Land (SEBAL), with the objective to generate ET time series of high spatial resolution and reliable temporal distribution at watershed scales. First, SEBAL is employed to yield estimates of ET for the Baiyangdian watershed in a semihumid climatic zone in north China on cloud‐free days, where there exists the complementary relationship (CR) between actual ET and pan ET. These estimates constitute input to the GG model to inversely derive the relationship between the relative evaporation and the relative drying power of the air. Second, the modified GG model is used to yield ET time series on a daily basis simply by using routine meteorological data and Moderate Resolution Imaging Spectroradiometer (MODIS) albedo and leaf area index products. Results suggest that the modified GG model that has incorporated remotely sensed ET can effectively extend remote sensing based ET to days without images and improve spatial representation of ET at watershed scales. Utility of the evaporative fraction method and the crop coefficients approaches to extrapolate ET time series depends largely on the number and interval of good quality satellite images. Comparison of ET time series from the two techniques and the proposed integration method for days with daily net radiation larger than 100 W m−2 and corresponding pan ET clearly shows that only the integration method can exhibit an asymmetric CR at the watershed scale and daily time scale. Validation performed using hydrologic budget calculations indicate that the proposed method has the highest accuracy in terms of annual estimates of ET for both watersheds in north China.
Bayesian model averaging for emergency response atmospheric dispersion multimodel ensembles: Is it really better? How many data are needed? Are the weights portable?
Authors: Potempski S. , Galmarini S. , Riccio A. , Giunta G.
Published: November 2010

In this paper, we investigate applicability of Bayesian model averaging (BMA) methodology to atmospheric dispersion multimodel ensemble system within the context of emergency response applications. The BMA method can be used both to evaluate model predictions and to combine model results using BMA weighing factors. We analyze time evolution of BMA weights and include a detailed quantitative comparison of different combinations of model results performed by the means of statistical indicators. The analysis allows us to identify similarities and differences among different combined models. Finally, we question the portability of BMA weights among various cases. From the analysis it follows that BMA can be applied in considered problems; however, the median of the model results also performs well and produces more conservative results.
Environmental proteomics of microbial plankton in a highly productive coastal upwelling system
Authors: Sowell Sarah M , Abraham Paul E , Shah Manesh , Verberkmoes Nathan C , Smith Daniel P , Barofsky Douglas F , Giovannoni Stephen J
Published: November 2010

Metaproteomics is one of a suite of new approaches providing insights into the activities of microorganisms in natural environments. Proteins, the final products of gene expression, indicate cellular priorities, taking into account both transcriptional and posttranscriptional control mechanisms that control adaptive responses. Here, we report the proteomic composition of the < 1.2 μm fraction of a microbial community from Oregon coast summer surface waters, detected with two-dimensional liquid chromatography coupled with electrospray tandem mass spectrometry. Spectra corresponding to proteins involved in protein folding and biosynthesis, transport, and viral capsid structure were the most frequently detected. A total of 36% of all the detected proteins were best matches to the SAR11 clade, and other abundant coastal microbial clades were also well represented, including the Roseobacter clade (17%), oligotrophic marine gammaproteobacteria group (6%), OM43 clade (1%). Viral origins were attributed to 2.5% of proteins. In contrast to oligotrophic waters, phosphate transporters were not highly detected in this nutrient-rich system. However, transporters for amino acids, taurine, polyamines and glutamine synthetase were among the most highly detected proteins, supporting predictions that carbon and nitrogen are more limiting than phosphate in this environment. Intriguingly, one of the highly detected proteins was methanol dehydrogenase originating from the OM43 clade, providing further support for recent reports that the metabolism of one-carbon compounds by these streamlined methylotrophs might be an important feature of coastal ocean biogeochemistry.
Correlating carbon monoxide oxidation with cox genes in the abundant Marine Roseobacter Clade
Authors: Cunliffe Michael
Published: November 2010

The Marine Roseobacter Clade (MRC) is a numerically and biogeochemically significant component of the bacterioplankton. Annotation of multiple MRC genomes has revealed that an abundance of carbon monoxide dehydrogenase (CODH) cox genes are present, subsequently implying a role for the MRC in marine CO cycling. The cox genes fall into two distinct forms based on sequence analysis of the coxL gene; forms I and II. The two forms are unevenly distributed across the MRC genomes. Most (18/29) of the MRC genomes contain only the putative form II coxL gene. Only 10 of the 29 MRC genomes analysed have both the putative form II and the definitive form I coxL. None have only the form I coxL. Genes previously shown to be required for post-translational maturation of the form I CODH enzyme are absent from the MRC genomes containing only form II. Subsequent analyses of a subset of nine MRC strains revealed that only MRC strains with both coxL forms are able to oxidise CO.
Effect of formaldehyde on cell proliferation and death
Authors: Szende Béla , Tyihák Ernő
Published: November 2010

Formaldehyde (HCHO) may reach living organisms as an exogenous agent or produced within cells. The so‐called formaldehydogenic compounds like S‐adenosyl‐l‐methionine, N‐hydroxymethyl‐l‐arginine, 1′‐methyl ascorbigen, methanol, E‐N‐trimethyl lysine and methylamine are special exogenous sources of HCHO. Endogenous HCHO can be formed from hydroxymethyl groups during enzymatic methylation and demethylation processes. HCHO, as a highly reactive compound, is considered to be involved in the induction of apoptosis, consequently in the pathogenesis of atherosclerosis and neurodegenerative processes. The biological action of HCHO is dose‐dependent. In vitro studies on tumour cell and endothelial cell cultures showed that HCHO in the concentration of 10.0 mM caused necrotic cell death, 1.0 mM resulted in enhanced apoptosis and reduced mitotic activity, while 0.5 and 0.1 mM enhanced cell proliferation and reduced apoptotic activity. Among formaldehydogenic compounds N‐hydroxymethyl‐l‐arginine, 1′‐methyl ascorbigen and the HCHO donor resveratrol may be considered as potential inhibitors of cell proliferation. Endogenous HCHO in plants apparently play a role in regulation of apoptosis and cell proliferation. The genotoxic and carcinogentic effects of HCHO is due to production of DNA—protein cross‐links. Low doses of HCHO, reducing apoptotic activity may also accumulate cells with such cross‐links. Experimental data point to the possible therapeutic use of methylated lysine residues and methylated arginine residues in the case of neoplasms.
Clinical Response to Questions Regarding Outcomes and Therapy Efficacy
Authors: Donaher Joseph , Gurrister Tom , Wollman Irving , Mackesey Tim , Burnett Michelle L.
Published: November 2010

Parents of children who stutter and adults who stutter frequently ask speech-language pathologists to predict whether or not therapy will work. Even though research has explored risk-factors related to persistent stuttering, there remains no way to determine how an individual will react to a specific therapy program. This paper presents various clinicians’answers to the question, “What do you tell parents or adults who stutter when they ask about cure rates, outcomes, and therapy efficacy?”
Ethical and Clinical Implications of Pseudostuttering
Authors: Hughes Stephanie
Published: November 2010

Purpose: Pseudostuttering is a form of disability simulation that often id used in fluency disorders courses to create empathy for people who stutter. The purpose of this study was to examine the ethical implications of pseudostuttering and to determine whether extending the duration of pseudostuttering activities is more beneficial for students’ clinical education.

Method: Twenty students in a graduate fluency disorders course engaged in public pseudostuttering for 6 weeks. Each student completed 30 pseudostuttering experiences during the experiment. Data were gathered in the form of quantitative checklists and open-ended journal entries. Descriptive and Chi-square statistics were used to identify how students’ thoughts, emotions, and behaviors changed on a weekly basis. Thematic analysis of journal entries was also conducted.

Results: Anxiety ratings decreased for every additional week of pseudostuttering. Decreased emotionality, increased clinical insights, and more willingness to pseudostutter in increasingly challenging contexts were considered benefits of extended pseudostuttering practice.

Conclusions: More opportunities to practice pseudostuttering appear to correspond with increased benefits for fluency disorders students. While any disability simulation is prone to criticism on the grounds that it lacks realism, instructors of fluency disorders courses can create more ethical and clinically relevant learning opportunities by asking students to pseudostutter repeatedly.
Postoperative Care of the Facial Laceration
Authors: Medel Nicholas , Panchal Neeraj , Ellis Edward
Published: November 2010

The purpose of this investigation is to examine factors involved in the postoperative care of traumatic lacerations. An evidence-based comprehensive literature review was conducted. There are a limited number of scientifically proven studies that guide surgeons and emergency room physicians on postoperative care. Randomized controlled trials must be conducted to further standardize the postoperative protocol for simple facial lacerations.
Treatment of Palatal Fractures by Osteosynthesis with 2.0-mm Locking Plates as External Fixator
Authors: Cienfuegos Ricardo , Sierra Eduardo , Ortiz Benjamin , Fernández Gerardo
Published: November 2010

Treatment options for palatal fractures range from orthodontic braces, acrylic bars, and arch bars for maxillomandibular fixation to internal fixation, with plates and screws placed under the palate mucosa and periosteum, together with pyriform aperture or alveolar plating plus buttress reconstruction. Forty-five patients, ages 4 to 56, were treated using medium- or high-profile locking plates placed over the palatal mucosa as an external fixator for palatal fractures, together with treatment for other associated facial fractures. In open fractures, plates were placed after approximating the edges of the mucosal wounds. Plates and screws for palate fixation were removed at 12 weeks, when computed tomography scans provided evidence of fracture healing. All palatal fractures healed by 12 weeks, with no cases of mucosal necrosis, bone exposure, fistulae, or infections. This approach achieves adequate stability, reduces the risk of bone and mucosal necrosis, and promotes healing of mucosal wounds in case of open fractures.
Experience with the Use of Prebent Plates for the Reconstruction of Mandibular Defects
Authors: Salgueiro Martin I. , Stevens Mark R.
Published: November 2010

Bending of large titanium plates for mandibular reconstruction is a tedious task. This is usually done by trial and error over an intraoperatively bent template. By means of rapid prototype technology, accurate three-dimensional models can be obtained. Using these models, it is possible to design, obtain, and adapt custom hardware for individual surgical cases. Reductions of operating room time when using this technology have been reported from 17% to 60%, with an average of 20%. This translates to reduction of cost and risks, improving the overall surgical outcome. The purpose of this article is to establish the indications and contraindication for the use three-dimensional models and prebent plates. We present our experience with five cases in which prebent reconstruction plates were used for mandibular reconstruction. No significant complications occurred, and satisfactory results were achieved in all cases. We found that the models required to obtain the hardware are extremely accurate, have multiple reported applications, and represent a valuable surgical tool in the planning and execution of reconstructive surgery.
Synthesis, Characterization and Anticancer Activity of Porphyrin-Containing Organometallic Cubes
Authors: Barry Nicolas P. E. , Zava Olivier , Dyson Paul J. , Therrien Bruno
Published: November 2010

Self‐assembly of 5,10,15,20‐tetra(4‐pyridyl)porphyrin (tpp‐H2) and 5,10,15,20‐tetra(4‐pyridyl)porphyrin‐M(ii) (M = Ni (tpp‐Ni); Zn (tpp‐Zn)) tetradentate panels with the dinuclear p‐cymene ruthenium clips [Ru2(p-cymene)2(C2O4)Cl2] and [Ru2(p-cymene)2(C6H2O4)Cl2] (C2O4 = oxalato; C6H2O4 = 2,5‐dioxydo‐1,4‐benzoquinonato) affords the cationic organometallic cubes: [Ru8(p-cymene)8(tpp‐H2)2(C2O4)4]8+ (1); [Ru8(p-cymene)8(tpp‐Ni)2(C2O4)4]8+ (2); [Ru8(p-cymene)8(tpp‐Zn)2(C2O4)4]8+ (3); [Ru8(p-cymene)8(tpp‐H2)2(C6H2O4)4]8+ (4); [Ru8(p-cymene)8(tpp‐Ni)2(C6H2O4)4]8+ (5); and [Ru8(p-cymene)8(tpp‐Zn)2(C6H2O4)4]8+ (6). In addition, the new dinuclear arene ruthenium 2,5‐dioxydo‐1,4‐benzoquinonato clips [Ru2(indane)2(C6H2O4)Cl2] (7) and [Ru2(nonylbenzene)2(C6H2O4)Cl2] (8) react in methanol with tpp‐H2 in the presence of silver triflate to afford the corresponding cationic cubes [Ru8(indane)8(tpp‐H2)2(C6H2O4)4]8+ (9) and [Ru8(nonylbenzene)8(tpp‐H2)2(C6H2O4)4]8+ (10) respectively. All cationic metalla‐cubes were isolated as triflate salts and characterized by NMR, infrared, electro‐spray mass spectrometry and UV‐visible spectroscopy. Moreover, the formation of unsymmetrical metalla‐cubes built using a mixture of the different porphyrin panels during the self‐assembly of the 2,5‐dioxydo‐1,4‐benzoquinonato metalla‐cubes, [Ru8(p-cymene)8(tpp‐H2)(tpp‐Ni)(C6H2O4)4]8+ (11), [Ru8(p-cymene)8(tpp‐H2)(tpp‐Zn)(C6H2O4)4]8+ (12), and [Ru8(p-cymene)8(tpp‐Ni)(tpp‐Zn)(C6H2O4)4]8+ (13), was studied by electro‐spray mass spectrometry. The cytotoxicities of all metalla‐cubes as well as the mixtures containing the unsymmetrical metalla‐cubes were established on human ovarian A2780 and A2780cisR cancer cell lines. All symmetrical compounds are equally cytotoxic (IC50 = 7–15 μM) (IC50 being the drug concentration necessary for 50% inhibition of cell viability) against both A2780 and cisplatin‐resistant A2780cisR cancer cells, with stronger cytotoxicities (IC50 = 2–5 μM) observed for the mixtures containing the unsymmetrical 2,5‐dioxydo‐1,4‐benzoquinonato metalla‐cubes.
Influence of the Arene Ligand and the Leaving Group on the Anticancer Activity of (Thio)maltol Ruthenium(II)–(η6-Arene) Complexes
Authors: Hanif Muhammad , Schaaf Patricia , Kandioller Wolfgang , Hejl Michaela , Jakupec Michael A. , Roller Alexander , Keppler Bernhard K. , Hartinger Christian G.
Published: November 2010

Maltol and its metal complexes have shown promising applications in medicinal chemistry. We report here the synthesis and characterization of Ru(η6-arene)(halido) coordination compounds bearing maltol or thiomaltol ligands and studies on their behaviour in aqueous solution, their reactions with the DNA model guanosine 5′-monophosphate (5′-GMP) and their in vitro anticancer activity in human tumour cell lines. The compounds hydrolyze rapidly and quantitatively to the respective aqua species by exchange of the halido ligand. With pKa values of >8, such species would also be present in biological media and they proved reactive to 5′-GMP. The thiomaltol compounds show promising in vitro activity with IC50 values (50% inhibitory concentration) in the low micromolar range, whereas activity of the maltol complexes is marginal. Variation of the arene ligand (benzene, toluene, p-cymene or biphenyl) resulted only in minor changes in activity.
A Bioorganometallic Chemistry Overview: From Cytochrome P450 Enzyme Metabolism of Organotin Compounds to Organorhodium-Hydroxytamoxifen Complexes with Potential Anti-Cancer Properties; A 37 Year Perspective at the Interface of Organometallic Chemistry and Biology
Authors: Fish Richard H.
Published: November 2010

A 37 year perspective on bioorganometallic chemistry studies, which included metabolism of organotin compounds with cytochrome P450 enzymes, and their biomimics; reactions of organorhodium aqua complexes with nucleobases, nucleosides, and nucleotides; supramolecular organorhodium-nucleobase complexes as hosts for aromatic amino acid and aromatic carboxylic acid guests; regioselective reduction of NAD+ biomimics with an organorhodium hydride; tandem catalysis of an organorhodium hydride reduction to provide a 1,4-NADH biomimic for horse liver dehydrogenase stereoselective reduction of achiral ketones to chiral alcohols, and oxidation reactions with cytochrome P450 enzymes; and organorhodium-hydroxytamoxifen pharmaceuticals, will be presented. Each of these areas of bioorganometallic chemistry will be briefly discussed in this personal synopsis of the new, important, and exciting field of bioorganometallic chemistry, and its impact on metal-based drug research.
Toxic diatoms and domoic acid in natural and iron enriched waters of the oceanic Pacific
Authors: Silver Mary W. , Bargu Sibel , Coale Susan L. , Benitez-Nelson Claudia R. , Garcia Ana C. , Roberts Kathryn J. , Sekula-Wood Emily , Bruland Kenneth W. , Coale Kenneth H.
Published: November 2010

Near-surface waters ranging from the Pacific subarctic (58°N) to the Southern Ocean (66°S) contain the neurotoxin domoic acid (DA), associated with the diatom
Pseudo-nitzschia
. Of the 35 stations sampled, including ones from historic iron fertilization experiments (SOFeX, IronEx II), we found
Pseudo-nitzschia
at 34 stations and DA measurable at 14 of the 26 stations analyzed for DA. Toxin ranged from 0.3 fg·cell
−1
to 2 pg·cell
−1
, comparable with levels found in similar-sized cells from coastal waters. In the western subarctic, descent of intact
Pseudo-nitzschia
likely delivered significant amounts of toxin (up to 4 μg of DA·m
−2
·d
−1
) to underlying mesopelagic waters (150–500 m). By reexamining phytoplankton samples from SOFeX and IronEx II, we found substantial amounts of DA associated with
Pseudo-nitzschia
. Indeed, at SOFeX in the Antarctic Pacific, DA reached 220 ng·L
−1
, levels at which animal mortalities have occurred on continental shelves. Iron ocean fertilization also occurs naturally and may have promoted blooms of these ubiquitous algae over previous glacial cycles during deposition of iron-rich aerosols. Thus, the neurotoxin DA occurs both in coastal and oceanic waters, and its concentration, associated with changes in
Pseudo-nitzschia
abundance, likely varies naturally with climate cycles, as well as with artificial iron fertilization. Given that iron fertilization in iron-depleted regions of the sea has been proposed to enhance phytoplankton growth and, thereby, both reduce atmospheric CO
2
and moderate ocean acidification in surface waters, consideration of the potentially serious ecosystem impacts associated with DA is prudent.
Structure and folding of a designed knotted protein
Authors: King Neil P. , Jacobitz Alex W. , Sawaya Michael R. , Goldschmidt Lukasz , Yeates Todd O.
Published: November 2010

A very small number of natural proteins have folded configurations in which the polypeptide backbone is knotted. Relatively little is known about the folding energy landscapes of such proteins, or how they have evolved. We explore those questions here by designing a unique knotted protein structure. Biophysical characterization and X-ray crystal structure determination show that the designed protein folds to the intended configuration, tying itself in a knot in the process, and that it folds reversibly. The protein folds to its native, knotted configuration approximately 20 times more slowly than a control protein, which was designed to have a similar tertiary structure but to be unknotted. Preliminary kinetic experiments suggest a complicated folding mechanism, providing opportunities for further characterization. The findings illustrate a situation where a protein is able to successfully traverse a complex folding energy landscape, though the amino acid sequence of the protein has not been subjected to evolutionary pressure for that ability. The success of the design strategy—connecting two monomers of an intertwined homodimer into a single protein chain—supports a model for evolution of knotted structures via gene duplication.
RNA editing changes the lesion specificity for the DNA repair enzyme NEIL1
Authors: Yeo Jongchan , Goodman Rena A. , Schirle Nicole T. , David Sheila S. , Beal Peter A.
Published: November 2010

Editing of the pre-mRNA for the DNA repair enzyme NEIL1 causes a lysine to arginine change in the lesion recognition loop of the protein. The two forms of NEIL1 are shown here to have distinct enzymatic properties. The edited form removes thymine glycol from duplex DNA 30 times more slowly than the form encoded in the genome, whereas editing enhances repair of the guanidinohydantoin lesion by NEIL1. In addition, we show that the NEIL1 recoding site is a preferred editing site for the RNA editing adenosine deaminase ADAR1. The edited adenosine resides in an A-C mismatch in a hairpin stem formed by pairing of exon 6 to the immediate upstream intron 5 sequence. As expected for an ADAR1 site, editing at this position is increased in human cells treated with interferon α. These results suggest a unique regulatory mechanism for DNA repair and extend our understanding of the impact of RNA editing.
Measurement of adherent cell mass and growth
Authors: Park Kidong , Millet Larry J. , Kim Namjung , Li Huan , Jin Xiaozhong , Popescu Gabriel , Aluru N. R. , Hsia K. Jimmy , Bashir Rashid
Published: November 2010

The characterization of physical properties of cells such as their mass and stiffness has been of great interest and can have profound implications in cell biology, tissue engineering, cancer, and disease research. For example, the direct dependence of cell growth rate on cell mass for individual adherent human cells can elucidate the mechanisms underlying cell cycle progression. Here we develop an array of micro-electro-mechanical systems (MEMS) resonant mass sensors that can be used to directly measure the biophysical properties, mass, and growth rate of single adherent cells. Unlike conventional cantilever mass sensors, our sensors retain a uniform mass sensitivity over the cell attachment surface. By measuring the frequency shift of the mass sensors with growing (soft) cells and fixed (stiff) cells, and through analytical modeling, we derive the Young’s modulus of the unfixed cell and unravel the dependence of the cell mass measurement on cell stiffness. Finally, we grew individual cells on the mass sensors and measured their mass for 50+ hours. Our results demonstrate that adherent human colon epithelial cells have increased growth rates with a larger cell mass, and the average growth rate increases linearly with the cell mass, at 3.25%/hr. Our sensitive mass sensors with a position-independent mass sensitivity can be coupled with microscopy for simultaneous monitoring of cell growth and status, and provide an ideal method to study cell growth, cell cycle progression, differentiation, and apoptosis.
The major α-tubulin K40 acetyltransferase αTAT1 promotes rapid ciliogenesis and efficient mechanosensation
Authors: Shida Toshinobu , Cueva Juan G. , Xu Zhenjie , Goodman Miriam B. , Nachury Maxence V.
Published: November 2010

Long-lived microtubules found in ciliary axonemes, neuronal processes, and migrating cells are marked by α-tubulin acetylation on lysine 40, a modification that takes place inside the microtubule lumen. The physiological importance of microtubule acetylation remains elusive. Here, we identify a BBSome-associated protein that we name αTAT1, with a highly specificα-tubulin K40acetyltransferase activity and a catalytic preference for microtubules over free tubulin. In mammalian cells, the catalytic activity of αTAT1 is necessary and sufficient for α-tubulin K40 acetylation. Remarkably, αTAT1 is universally and exclusively conserved in ciliated organisms, and is required for the acetylation of axonemal microtubules and for the normal kinetics of primary cilium assembly. InCaenorhabditis elegans, microtubule acetylation is most prominent in touch receptor neurons (TRNs) and MEC-17, a homolog of αTAT1, and its paralog αTAT-2 are required for α-tubulin acetylation and for two distinct types of touch sensation. Furthermore, in animals lacking MEC-17, αTAT-2, and the soleC. elegansK40α-tubulin MEC-12, touch sensation can be restored by expression of an acetyl-mimic MEC-12[K40Q]. We conclude that αTAT1 is the major and possibly the sole α-tubulin K40 acetyltransferase in mammals and nematodes, and that tubulin acetylation plays a conserved role in several microtubule-based processes.
Generation of a consensus protein domain dictionary
Authors: Schaeffer R. Dustin , Jonsson Amanda L. , Simms Andrew M. , Daggett Valerie
Published: November 2010

Motivation: The discovery of new protein folds is a relatively rare occurrence even as the rate of protein structure determination increases. This rarity reinforces the concept of folds as reusable units of structure and function shared by diverse proteins. If the folding mechanism of proteins is largely determined by their topology, then the folding pathways of members of existing folds could encompass the full set used by globular protein domains.

Results: We have used recent versions of three common protein domain dictionaries (SCOP, CATH and Dali) to generate a consensus domain dictionary (CDD). Surprisingly, 40% of the metafolds in the CDD are not composed of autonomous structural domains, i.e. they are not plausible independent folding units. This finding has serious ramifications for bioinformatics studies mining these domain dictionaries for globular protein properties. However, our main purpose in deriving this CDD was to generate an updated CDD to choose targets for MD simulation as part of our dynameomics effort, which aims to simulate the native and unfolding pathways of representatives of all globular protein consensus folds (metafolds). Consequently, we also compiled a list of representative protein targets of each metafold in the CDD.

Availability and implementation: This domain dictionary is available at www.dynameomics.org.

Contact:  daggett@u.washington.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Fast and efficient dynamic nested effects models
Authors: Fröhlich Holger , Praveen Paurush , Tresch Achim
Published: November 2010

Motivation: Targeted interventions in combination with the measurement of secondary effects can be used to computationally reverse engineer features of upstream non-transcriptional signaling cascades. Nested effect models (NEMs) have been introduced as a statistical approach to estimate the upstream signal flow from downstream nested subset structure of perturbation effects. The method was substantially extended later on by several authors and successfully applied to various datasets. The connection of NEMs to Bayesian Networks and factor graph models has been highlighted.

Results: Here, we introduce a computationally attractive extension of NEMs that enables the analysis of perturbation time series data, hence allowing to discriminate between direct and indirect signaling and to resolve feedback loops.

Availability: The implementation (R and C) is part of the Supplement to this article.

Contact:  frohlich@bit.uni-bonn.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
Sevoflurane-induced Preconditioning
Authors: Fräßdorf Jan , Huhn Ragnar , Weber Nina C. , Ebel Dirk , Wingert Nadja , Preckel Benedikt , Toma Octavian , Schlack Wolfgang , Hollmann Markus W.
Published: November 2010

Background

Sevoflurane induces preconditioning (SevoPC). The effect of aprotinin and the involvement of endothelial nitric-oxide synthase (NOS) on SevoPC are unknown. We investigated (1) whether SevoPC is strengthened by multiple preconditioning cycles, (2) whether SevoPC is blocked by aprotinin, and (3) whether endothelial NOS plays a crucial role in SevoPC.

Methods

Anesthetized male Wistar rats were randomized to 15 groups (each n = 6) and underwent 25-min regional myocardial ischemia and 2-h reperfusion. Controls were not treated further. Preconditioning groups inhaled 1 minimum alveolar concentration of sevoflurane for 5 min (SEVO-I), twice for 5 min each (SEVO-II), three times for 5 min each (SEVO-III), or six times for 5 min each (SEVO-VI). Aprotinin was administered with and without sevoflurane. Involvement of endothelial NOS was determined with the nonspecific NOS blocker N-nitro-l-arginine-methyl-ester, the specific neuronal NOS blocker 7-nitroindazole, and the specific inducible NOS blocker aminoguanidine.

Results

SevoPC reduced infarct size in all protocols (SEVO-I, 42 ± 6%; SEVO-II, 33 ± 4%; SEVO-III, 11 ± 5%; SEVO-VI, 16 ± 4%; all P < 0.001 vs. control, 67 ± 3%) and was least after three and six cycles of sevoflurane (P < 0.001 vs. SEVO-II and -I, respectively). Aprotinin alone had no effect on infarct size but blocked SevoPC. N-nitro-l-arginine-methyl-ester abolished SevoPC (67 ± 4%; P < 0.05 vs. SEVO-III). Aminoguanidine and 7-nitroindazole blocked SevoPC only partially (25 ± 6 and 31 ± 6%, respectively; P < 0.05 vs. SEVO-III and control). SevoPC induced endothelial NOS phosphorylation, which was abrogated by aprotinin.

Conclusion

SevoPC is strengthened by multiple preconditioning cycles, and phosphorylation of endothelial NOS is a crucial step in mediating SevoPC. These effects are abolished by aprotinin.