bluuebunny/crossref_metadata_2025 huggingface dataset:
A global machine learning based scoring function for protein structure prediction
Authors: Faraggi Eshel , Kloczkowski Andrzej
Published: October 2013

We present a knowledge‐based function to score protein decoys based on their similarity to native structure. A set of features is constructed to describe the structure and sequence of the entire protein chain. Furthermore, a qualitative relationship is established between the calculated features and the underlying electromagnetic interaction that dominates this scale. The features we use are associated with residue–residue distances, residue–solvent distances, pairwise knowledge‐based potentials and a four‐body potential. In addition, we introduce a new target to be predicted, the fitness score, which measures the similarity of a model to the native structure. This new approach enables us to obtain information both from decoys and from native structures. It is also devoid of previous problems associated with knowledge‐based potentials. These features were obtained for a large set of native and decoy structures and a back‐propagating neural network was trained to predict the fitness score. Overall this new scoring potential proved to be superior to the knowledge‐based scoring functions used as its inputs. In particular, in the latest CASP (CASP10) experiment our method was ranked third for all targets, and second for freely modeled hard targets among about 200 groups for top model prediction. Ours was the only method ranked in the top three for all targets and for hard targets. This shows that initial results from the novel approach are able to capture details that were missed by a broad spectrum of protein structure prediction approaches. Source codes and executable from this work are freely available at http://mathmed.org/#Software and http://mamiris.com/. Proteins 2014; 82:752–759. © 2013 Wiley Periodicals, Inc.
Nitric Oxide Controls Fat Deposition in Dystrophic Skeletal Muscle by Regulating Fibro-Adipogenic Precursor Differentiation
Authors: Cordani Nicoletta , Pisa Viviana , Pozzi Laura , Sciorati Clara , Clementi Emilio
Published: October 2013

Duchenne muscular dystrophy (DMD) is an hereditary disease characterized by loss of muscle fibers and their progressive substitution by fat and fibrous tissue. Mesenchymal fibro-adipogenic progenitors (FAPs) expressing the platelet-derived growth factor receptor alpha (PDGFRα) are an important source of fibrosis and adipogenesis in dystrophic skeletal muscle. Among the therapies suggested for dystrophy are those based on nitric oxide (NO) donating drugs, the administration of which slows disease progression. NO has been shown to act by enhancing the regenerative potential of the diseased muscle. Whether it acts also by inhibiting fibrosis and adipogenesis was not known. Here, we show in vitro that NO regulates FAP fate through inhibition of their differentiation into adipocytes. In mdx mice, an animal model of DMD, treatment with the NO donating drug molsidomine reduced the number of PDGFRα+ cells as well as the deposition of both skeletal muscle fat and connective tissues. Inhibition of adipogenesis was due to NO-induced increased expression of miR-27b leading to downregulation of peroxisome proliferator-activated receptors gamma (Pparγ1) expression in a pathway independent of cGMP generation. These findings reveal an additional effect of NO in dystrophic muscle that conceivably synergizes with its known effects on regeneration improvement and explain why NO-based therapies appear effective in the treatment of muscular dystrophy. Stem Cells  2014;32:874–885
Pten Loss in Olig2 Expressing Neural Progenitor Cells and Oligodendrocytes Leads to Interneuron Dysplasia and Leukodystrophy
Authors: Maire Cécile L. , Ramkissoon Shakti , Hayashi Marika , Haidar Sam , Ramkissoon Lori , DiTomaso Emmanuelle , Ligon Keith L.
Published: October 2013

Therapeutic modulation of phosphatidylinositol 3-kinase (PI3K)/PTEN signaling is currently being explored for multiple neurological indications including brain tumors and seizure disorders associated with cortical malformations. The effects of PI3K/PTEN signaling are highly cell context dependent but the function of this pathway in specific subsets of neural stem/progenitor cells generating oligodendroglial lineage cells has not been fully studied. To address this, we created Olig2-cre:Ptenfl/fl mice that showed a unique pattern of Pten loss and PI3K activation in Olig2-lineage cells. Olig2-cre:Ptenfl/fl animals progressively developed central nervous system white matter hypermyelination by 3 weeks of age leading to later onset leukodystrophy, chronic neurodegeneration, and death by 9 months. In contrast, during immediate postnatal development, oligodendroglia were unaffected but abnormal and accelerated differentiation of lateral subventricular zone stem cells produced calretinin-positive interneuron dysplasia. Neural stem cells isolated from Olig2-cre:Ptenfl/fl mice also exhibited accelerated differentiation and proliferation into calretinin-positive interneurons and oligodendrocytes indicating such effects are cell autonomous. Opposition of the pathway by treatment of human primary neural progenitor cells (NPCs) with the PI3K inhibitor, NVP-BKM120, blocked in vitro differentiation of neurons and oligodendroglia indicating PI3K/PTEN effects on NPCs can be bidirectional. In summary, our results suggest Pten is a developmental rheostat regulating interneuron and oligodendroglial differentiation and support testing of PI3K modulating drugs as treatment for developmental and myelination disorders. However, such agents may need to be administered at ages that minimize potential effects on early stem/progenitor cell development. Stem Cells  2014;32:313–326
Construction of a convenient system for easily screening inhibitors of mutated influenza virus neuraminidases
Authors: Shigemori Tomohiro , Nagayama Mitsuru , Yamada Junki , Miura Natsuko , Yongkiettrakul Suganya , Kuroda Kouichi , Katsuragi Tohoru , Ueda Mitsuyoshi
Published: October 2013

Neuraminidase (NA) is a surface glycoprotein produced by the influenza virus. Specific NA mutations that confer resistance to anti‐viral drugs have been reported. The aim of this study was to demonstrate quick preparation of the mutated NAs using the yeast surface display and its applicability for screening inhibitors. Plasmids encoding the head domain of wild‐type and drug‐resistant NAs were constructed and introduced into yeast, and these were successfully displayed on the yeast surface, with biochemical properties similar to the native virus NAs. This system using mutated NAs‐displaying yeast provides an efficient and convenient tool for screening novel inhibitors against the drug‐resistant influenza virus.
Laminar–turbulent transition induced by a discrete roughness element in a supersonic boundary layer
Authors: De Tullio N. , Paredes P. , Sandham N. D. , Theofilis V.
Published: October 2013

The linear instability and breakdown to turbulence induced by an isolated roughness element in a boundary layer at Mach $2. 5$, over an isothermal flat plate with laminar adiabatic wall temperature, have been analysed by means of direct numerical simulations, aided by spatial BiGlobal and three-dimensional parabolized (PSE-3D) stability analyses. It is important to understand transition in this flow regime since the process can be slower than in incompressible flow and is crucial to prediction of local heat loads on next-generation flight vehicles. The results show that the roughness element, with a height of the order of the boundary layer displacement thickness, generates a highly unstable wake, which is composed of a low-velocity streak surrounded by a three-dimensional high-shear layer and is able to sustain the rapid growth of a number of instability modes. The most unstable of these modes are associated with varicose or sinuous deformations of the low-velocity streak; they are a consequence of the instability developing in the three-dimensional shear layer as a whole (the varicose mode) or in the lateral shear layers (the sinuous mode). The most unstable wake mode is of the varicose type and grows on average ${\sim }17\hspace{0.167em} \% $ faster than the most unstable sinuous mode and ${\sim }30$ times faster than the most unstable boundary layer mode occurring in the absence of a roughness element. Due to the high growth-rates registered in the presence of the roughness element, an amplification factor of $N= 9$ is reached within ${\sim }50$ roughness heights from the roughness trailing edge. The independently performed Navier–Stokes, spatial BiGlobal and PSE-3D stability results are in excellent agreement with each other, validating the use of simplified theories for roughness-induced transition involving wake instabilities. Following the linear stages of the laminar–turbulent transition process, the roll-up of the three-dimensional shear layer leads to the formation of a wedge of turbulence, which spreads laterally at a rate similar to that observed in the case of compressible turbulent spots for the same Mach number.
Epidemiological review of toxoplasmosis in humans and animals in Romania
Authors: DUBEY J. P. , HOTEA I. , OLARIU T. R. , JONES J. L. , DĂRĂBUŞ G.
Published: October 2013

Infections by the protozoan parasite Toxoplasma gondii are widely prevalent in humans and other animals worldwide. However, information from eastern European countries is sketchy. In many eastern European countries, including Romania, it has been assumed that chronic T. gondii infection is a common cause of infertility and abortion. For this reason, many women in Romania with these problems were needlessly tested for T. gondii infection. Most papers on toxoplasmosis in Romania were published in Romanian in local journals and often not available to scientists in other countries. Currently, the rate of congenital infection in Romania is largely unknown. In addition, there is little information on genetic characteristics of T. gondii or prevalence in animals and humans in Romania. In the present paper we review prevalence, clinical spectrum and epidemiology of T. gondii in humans and animals in Romania. This knowledge should be useful to biologists, public health workers, veterinarians and physicians.
Cognitive impairment in depression: a systematic review and meta-analysis
Authors: Rock P. L. , Roiser J. P. , Riedel W. J. , Blackwell A. D.
Published: October 2013

Background

This review aimed to address the question of whether cognitive impairment should be considered a core feature of depression that may be a valuable target for treatment.

Method

We conducted a systematic review and meta-analysis of cognitive function, assessed with a single neuropsychological test battery, the Cambridge Neuropsychological Test Automated Battery (CANTAB), in patients with depression during symptomatic and remitted states. Inclusion of studies comparing patients remitted from depression and controls enabled us to investigate whether cognitive impairment persists beyond episodes of low mood in depression.

Results

Our meta-analysis revealed significant moderate cognitive deficits in executive function, memory and attention in patients with depression relative to controls (Cohen'sdeffect sizes ranging from −0.34 to −0.65). Significant moderate deficits in executive function and attention (Cohen'sdranging from −0.52 to −0.61) and non-significant small/moderate deficits in memory (Cohen'sdranging from −0.22 to −0.54) were found to persist in patients whose depressive symptoms had remitted, indicating that cognitive impairment occurs separately from episodes of low mood in depression.

Conclusions

Both low mood and cognitive impairment are associated with poor psychosocial functioning. Therefore, we argue that remediation of cognitive impairment and alleviation of depressive symptoms each play an important role in improving outcome for patients with depression. In conclusion, this systematic review and meta-analysis demonstrates that cognitive impairment represents a core feature of depression that cannot be considered an epiphenomenon that is entirely secondary to symptoms of low mood and that may be a valuable target for future interventions.
Norfolk Implements of Palæolithic “Cave” Types
Authors: Clarke W. G.
Published: October 2013

M. Rutot has pointed out that in the centre and south of France all the Palæolithic industries since the Chellean, and up to and including implements of the Neolithic period, lie intermingled on the surface, and in the last part of our “Proceedings” Dr. Sturge has given cogent reasons for considering some of our surface implements in East Anglia to be late Palæolithic, of “cave” types. Mr. Reginald Smith, F.S.A., has also adopted this view, and elaborated it by allotting the well-defined “Cissbury type” implements to the Aurignacian period. In looking through some thousands of Norfolk implements I have been struck by the scarcity—omitting the “Cissbury” specimens—of the types described as resembling those from the French caves, and by their much greater frequency in South-West Norfolk than in other parts of the county, though this applies to practically every industry, and is probably due to a variety of causes, geological and otherwise.
A Defence of the “Humanity” of the Pre-River Valley Implements of the Ipswich District
Authors: Moir J. Reid
Published: October 2013

In the second part of our Proceedings, I was able to give an account of various experiments with flints under natural percussion and pressure, and to show wherein the fractures produced by these means differ from those resulting from human blows. This paper, which was an accumulation of concrete facts, was written with a view to dispelling in some measure the atmosphere of uncertainty which for so many years had surrounded the important subject of the greater antiquity of man.

I now propose to supplement, as it were, the results obtained by my experiments by replying to the various objections which have been raised as to the “humanity” of the pre-Palæolithic implements I have discovered, and to show why in my opinion these objections are by no means insurmountable. I intend to confine myself to a defence of the implements found in my own particular district, because after several years' continual study of these specimens, and the beds in which they occur, I feel able to speak with some amount of confidence about them.
A New Celt-Making Floor at Grime's Graves
Authors: Richardson Derek
Published: October 2013

This floor, No. 46, was situated in the open field close to the North border of the plantation, about 50 yards N.E. of Pit 1. Excavations carried out by Mrs. Richardson and myself revealed the presence of a filled-in pit, of which there was no surface indication, the field having been levelled down for cultivation. The hole dug measured about 11 ft. each way, with a maximum depth of 5 ft. At the bottom on one side was a great tip of hard tabular chalk blocks, shot in from the N.E.; on the other side was a tip of sand shot in from the S.W.; and in the V-shaped depression between these two was a mass of flints without any matrix, most of them of great size, the majority covered with a fungus-like coating of carbonate of lime redeposited from solution. This layer reached a thickness of 3½ ft. in one part, thinning out gradually towards the E. side, where it was only a few inches thick. It was almost entirely sealed in by a small tip of chalk blocks and rubble shot in from the N.E., overlain in its turn by a thin layer of flints, which in one or two places rested directly on the main flint layer.
A Settlement of the Early Iron Age at Abington Pigotts, Cambs., and its Subsequent History; as Evidenced by Objects Preserved in the Pigott Collection
Authors: Fox Cyril
Published: October 2013

It is remarkable that so few attempts have been made to illustrate continuity of settlement on a given site through successive culture phases in East Anglia. No more valuable study could be undertaken by any field archæologist, than the careful examination of successive deposits on such a site. Especially useful would be the analysis of the transitional phases, showing the extent to which the art and craft-workers of one period influenced the technique and style of their successors and descendants; such a study should also throw light on the material, social and economic effects on the peasantry of the district of invasion and conquest, an evil from which East Anglia seems to have suffered every 500 years or so from about 1000 B.C. onwards. I cannot offer you, first hand, such a study; but it may be worth while, as an approach to the ideal, to illustrate a collection of objects from a settlement which seems to have been occupied during three (or four) culture phases for a total period of some 2,000 years.
The Palaeolithic Implements of Nidderdale, Yorkshire
Authors: Collins E. R.
Published: October 2013

The discovery of a large hand-axe of the Chelles period in the bed of the river Nidd at Goyden Pot Hole in 1922 has, after eight years careful work, established the fact by the results obtained, that Palæolithıc man lived in Yorkshire from the earliest times. This paper concerns only the upper part of Nidderdale, from Pateley Bridge to the source of the Nidd on Great Whernside. For the privilege of examining this large tract of country my thanks are due to the late Mr. T. E. Yorke, Col. C. J. Huskinson, Mr. H. A. Ramsden, Mr. W. Nicholson, and Mr. L. Mitchell.

As the nature of the country in which the implements have been found is so different from all other sites where implements of the same periods exist in England, a short description of it will not be out of place.

Nidderdale, like all the other Yorkshire dales, has been carved out by the glaciers of the Pleistocene period, and the course which the river follows is the same as that of the glaciers. The Nidd rises in Great Whernside at the height of over 2,000 ft., and by the time it reaches Pateley Bridge, some 15 miles from its source, it is only 383 ft. above sea. The fall of the hills corresponds more or less with this, the top of Great Whernside being 2,310 ft. O.D., and the moors at Pateley Bridge being 1,100-ft. to 1,050 ft. O.D. All down the dale on both sides many streams flow into the river: these have cut out deep narrow valleys, known locally as gills, and in doing so have exposed the lateral moraines which exist there.
The Presidential Address for 1932: The Culture of Pliocene Man
Authors: Moir J. Reid
Published: October 2013

It is now close upon twenty-five years since the first flints from beneath the Red Crag of Suffolk—and claimed to have been flaked by man—were placed before the scientific world. During the period of time which has elapsed since 1907, a great deal of careful excavation, carried out by means of generous financial support given by the Royal Society, the Percy Sladen Fund, the Wellcome Historical Medical Museum, the Field Museum of Chicago and other Institutions, has been undertaken, and in consequence, a very considerable body of knowledge regarding the archaeological, and other contents of the Suffolk Bone Bed, has been accumulated.

I propose, therefore, to take as the subject of my Presidential Address, “The Culture of Pliocene Man;” to place before you the evidence which makes it possible to use such a title in describing the sub-Red Crag artefacts, and to draw your attention to certain remarkable facts and conclusions relating to these specimens which must now be faced and considered. But it is necessary, first of all, to give a brief account of the Red Crag and the Suffolk Bone Bed (sometimes also called the Detritus Bed or the Nodule Bed) which underlies it, and in which the relics of man have been found.
A Hallstatt Settlement at West Harling, Norfolk
Authors: Apling H.
Published: October 2013

At the November Meeting last year I gave an account of some Bronze Age cooking places situated along the River Thet above East Harling. (Proc. P.S.E.A., Vol. VI, pt. IV, p.365). On continuing the exploration lower down the river, I came upon the peculiar mound known as Micklemoor Hill, West Harling. This is an isolated mound of glacial gravel in the middle of a long stretch of alluvium on the south side of the river, and is one mile S.W. by W. of East Harling Church. It is about 300 yards long, 150 yards wide and 25 ft. high, and is 100 yards from the river bank with its longer axis parallel to the river at this point, i.e., east and west. The Hill is grass-covered and given over, to rabbits, with the exception of the S.-E. corner, which, besides having been dug for sand and gravel, has on the top an eighteenth century ice-house surrounded by a few pines and firs.
Bell-Barrows
Authors: Grinsell L. V.
Published: October 2013

In the following study, the region dealt with is bounded on the north by the Thames, and on the west by the Avebury and Stonehenge areas. It consists therefore of Wiltshire, Hampshire, Berkshire, Surrey, Sussex and Kent, and a small portion of Dorset. The area contains about five thousand barrows, or ancient burial-mounds, about seven-eighths of which I have seen; it is believed therefore that the following details are fairly complete.
An assessment of ecological conditions and threats at the Ethiopian wintering site of the last known eastern colony of Critically Endangered Northern Bald IbisGeronticus eremita
Authors: SERRA G. , BRUSCHINI C. , PESKE L. , KUBSA A. , WONDAFRASH M. , LINDSELL J. A.
Published: October 2013

The long-range, migratory eastern relict population of Northern Bald IbisGeronticus eremitahas been steadily declining since the time of discovery in 2002, despite the protection programme in place at the breeding grounds in Syria. Assessing the ecological conditions and threats along the migration route and at the wintering site, both discovered in 2006, has become a priority for this “Critically Endangered” species. Adult ibises spent the winter at the same site on the central Ethiopian highland plateau, from August until mid-February during five consecutive winters (2006-2011). The wintering site was surveyed during four field visits and assessed through a spatial analysis of 1,067 satellite locations. The site is in an agro-pastoral landscape, inhabited by a settled community of people living in relatively poor and isolated conditions. Home range analysis based on kernel distributions showed that the bald ibises used a core range area of 9.1–19.0 km² (confirmed by direct visual observations in the field) and an extended range area of 61.0–126.1 km². These figures are c.20 and 60 times smaller, respectively, than those calculated for the breeding site in Syria. Eighty-one percent of the core area in Ethiopia was used in all five years confirming the birds’ fidelity to this wintering site. Ibises preferred to forage in wet or dry pastures and in recently cut hayfields, and avoided tall grass, uncut hayfields and cultivation. Despite dependence on human-created habitats, human disturbance observed in the field was minimal. The main short-term threat for the ibises was judged to be the potential raising of attention on the part of the local community specifically towards these few individual ibises. In the medium term, the main threat comes from the conversion of pastures into crops and the potential use of fertilisers and pesticides.
Efficacy of very low-dose prostaglandin E1 in duct-dependent congenital heart disease
Authors: Yucel Ilker K. , Cevik Ayhan , Bulut Mustafa O. , Dedeoğlu Reyhan , Demir İbrahim H. , Erdem Abdullah , Celebi Ahmet
Published: October 2013

Aim

The present study aims to define the lowest effective prostaglandin E1 dose in patients with inadequacy of pulmonary blood flow and/or intracardiac blood mixing and those with inadequate systemic blood flow.

Methods

Patients with inadequacy of both pulmonary blood flow and/or blood mixing (Group 1) and those with inadequate systemic blood flow (Group 2) were retrospectively evaluated in two separate groups with regard to the prostaglandin E1 starting dose given in the referring facility, the lowest and the highest dose administered in our centre, treatment duration, adverse effects, and administered treatment.

Results

No difference between the groups could be detected with respect to sex or birth weight (p=0.95 and 0.42, respectively). Group 1 and Group 2 were statistically similar in aspect of prostaglandin treatment duration (9.73±0.81 days versus 11.6±1.05 days, p=0.064). When compared with Group 2, the initial, maintenance and lowest efficient doses of prostaglandin E1 treatment were significantly lower and the titrated dose of prostaglandin E1 was significantly higher in Group 1 (p=0.001 for each).

Conclusion

Our findings indicate that the infusion of prostaglandin at a very low dose (0.003–0.005 mcg/kg/minute) is sufficient to maintain the patency of the ductus arteriosus. A higher dose of prostaglandin E1 may be necessary in patients with inadequate systemic blood flow.
Endothelial function state following repair of cyanotic congenital heart diseases
Authors: Sabri Mohammad Reza , Daryoushi Hooman , Gharipour Mojgan
Published: October 2013

Background

Repairing cyanotic congenital heart disease may be associated with preserving endothelial function. The present study aimed to evaluate vascular endothelial function in patients with repaired cyanotic congenital heart disease.

Methods

In a case–control study conducted in 2012 in Isfahan, Iran, 42 consecutive patients aged <35 years who had suffered from different types of cyanotic congenital heart disease and had undergone complete repair of their congenital heart defect were assessed in regard to their endothelial function state by measuring flow-mediated dilatation and other cardiac function indices. They were paired with 42 sex- and age-matched healthy controls.

Results

The mean flow-mediated dilatation was lower in patients with repaired cyanotic congenital heart disease than in the controls [6.14±2.78 versus 8.16±1.49 respectively (p<0.001)]. Significant adverse correlations were found between flow-mediated dilatation, age, and body mass indexes, in those who underwent repair surgery. In addition, flow-mediated dilatation had a positive association with the shortening fraction, ejection fraction, and tricuspid annular plane systolic excursion value, and it was also inversely associated with carotid intima-media thickness and the myocardial performance index. The mean of the flow-mediated dilatation was significantly higher in the group with tetralogy of Fallot along with complete repair before the age of 2.5 years and also in those patients with total anomalous pulmonary venous connection or transposition of the great arteries repaired with an arterial switch operation before 6 months of age, compared with the other two subgroups. This includes patients with a tetralogy of Fallot defect repaired after 4 years of age and those with complex cyanotic congenital heart disease that was repaired after 2.5 years of age (mean age at repair 9±6.1 years).

Conclusion

Early repair of a cyanotic defect can result in the protection of vascular endothelial function and prevent the occurrence of vascular accidents at an older age.
Quantitative Annular Dark Field Electron Microscopy Using Single Electron Signals
Authors: Ishikawa Ryo , Lupini Andrew R. , Findlay Scott D. , Pennycook Stephen J.
Published: October 2013

One of the difficulties in analyzing atomic resolution electron microscope images is that the sample thickness is usually unknown or has to be fitted from parameters that are not precisely known. An accurate measure of thickness, ideally on a column-by-column basis, parameter free, and with single atom accuracy, would be of great value for many applications, such as matching to simulations. Here we propose such a quantification method for annular dark field scanning transmission electron microscopy by using the single electron intensity level of the detector. This method has the advantage that we can routinely quantify annular dark field images operating at both low and high beam currents, and under high dynamic range conditions, which is useful for the quantification of ultra-thin or light-element materials. To facilitate atom counting at the atomic scale we use the mean intensity in an annular dark field image averaged over a primitive cell, with no free parameters to be fitted. To illustrate the potential of our method, we demonstrate counting the number of Al (or N) atoms in a wurtzite-type aluminum nitride single crystal at each primitive cell over the range of 3–99 atoms.
Design of orthogonal genetic switches based on a crosstalk map of σs, anti‐σs, and promoters
Authors: Rhodius Virgil A , Segall‐Shapiro Thomas H , Sharon Brian D , Ghodasara Amar , Orlova Ekaterina , Tabakh Hannah , Burkhardt David H , Clancy Kevin , Peterson Todd C , Gross Carol A , Voigt Christopher A
Published: October 2013

Cells react to their environment through gene regulatory networks. Network integrity requires minimization of undesired crosstalk between their biomolecules. Similar constraints also limit the use of regulators when building synthetic circuits for engineering applications. Here, we mapped the promoter specificities of extracytoplasmic function (ECF) σs as well as the specificity of their interaction with anti‐σs. DNA synthesis was used to build 86 ECF σs (two from every subgroup), their promoters, and 62 anti‐σs identified from the genomes of diverse bacteria. A subset of 20 σs and promoters were found to be highly orthogonal to each other. This set can be increased by combining the −35 and −10 binding domains from different subgroups to build chimeras that target sequences unrepresented in any subgroup. The orthogonal σs, anti‐σs, and promoters were used to build synthetic genetic switches in Escherichia coli. This represents a genome‐scale resource of the properties of ECF σs and a resource for synthetic biology, where this set of well‐characterized regulatory parts will enable the construction of sophisticated gene expression programs.
Large, high quality single-crystals of the new Topological Kondo Insulator, SmB6
Authors: Hatnean M. Ciomaga , Lees M. R. , Paul D. McK. , Balakrishnan G.
Published: October 2013

SmB6 has recently been predicted to be a Topological Kondo Insulator, the first strongly correlated heavy fermion material to exhibit topological surface states. High quality crystals are necessary to investigate the topological properties of this material. Single crystal growth of the rare earth hexaboride, SmB6, has been carried out by the floating zone technique using a high power xenon arc lamp image furnace. Large, high quality single-crystals are obtained by this technique. The crystals produced by the floating zone technique are free of contamination from flux materials and have been characterised by resistivity and magnetisation measurements. These crystals are ideally suited for the investigation of both the surface and bulk properties of SmB6.
Bounded synchronisation of singularly perturbed complex network with an application to power systems
Authors: Zhai Shidong , Yang Xiao‐Song
Published: October 2013

This study is concerned with the bounded synchronisation of singularly perturbed complex network. If the reduced network is boundedly synchronised, the authors obtain, by using partially contracting theory, an explicit bound for small perturbation parameter to guarantee the bounded synchronisation of singularly perturbed complex network. Moreover, the authors present a sufficient condition such that the reduced network is boundedly synchronised. Although this sufficient condition is difficult to test directly for general networks, it can be tested for power networks based on some existing results. The effectiveness of the proposed results is demonstrated via power networks.
Immunosignatures can predict vaccine efficacy
Authors: Legutki Joseph Barten , Johnston Stephen Albert
Published: October 2013

Significance

Vaccines have been the most important medical intervention developed, yet vaccines for many diseases are still needed. Despite its success, the process to develop a vaccine remains empirical, resting on measuring the number of vaccinees that incur or do not incur an infection. Here we test in the mouse flu model whether the “immunosignature” diagnostic technology could be applied to predict vaccine efficacy. Immunosignatures are produced by profiling the antibody repertoire of an individual on a chip arrayed with nonnatural sequence peptides. It is attractive in that it is a simple but comprehensive measure of the complexity of the humoral response. We found that immunosignatures are a promising approach to predicting whether a vaccine will confer protection.
Detection and mapping of 5-methylcytosine and 5-hydroxymethylcytosine with nanopore MspA
Authors: Laszlo Andrew H. , Derrington Ian M. , Brinkerhoff Henry , Langford Kyle W. , Nova Ian C. , Samson Jenny Mae , Bartlett Joshua J. , Pavlenok Mikhail , Gundlach Jens H.
Published: October 2013

Significance

Cells attach a methyl group (—CH
3
) to certain cytosines in DNA to control gene expression. These methylation patterns change over time and can be related to cell differentiation and diseases such as cancer. Existing methylation detection techniques are not ideal for clinical use. We pulled single-stranded DNA molecules through the biological pore MspA and found that ion currents passing through the pore reveal the methylation sites with high confidence. Hydroxymethylation, which differs from methylation by only one oxygen atom, also produces distinct signals. This technique can be developed into a research tool and may ultimately lead to clinical tests.
Error rates for nanopore discrimination among cytosine, methylcytosine, and hydroxymethylcytosine along individual DNA strands
Authors: Schreiber Jacob , Wescoe Zachary L. , Abu-Shumays Robin , Vivian John T. , Baatar Baldandorj , Karplus Kevin , Akeson Mark
Published: October 2013

Significance

Modification of cytosine bases in DNA can determine when genes are turned on in biological cells. These modifications are important during cell differentiation, embryogenesis, and aberrant cell growth in cancer. Here, we present a nanopore technique that permits direct detection of cytosine, 5-hydroxymethylcytosine, and 5-methylcytosine on individual synthetic DNA strands of known sequence. This technique focuses on three ionic current amplitudes that occur as an enzyme motor pulls the cytosine on a captured DNA strand through the nanopore. For genomic DNA, we predict that a given strand must be read 5–19 times to achieve cytosine methylation calls that are sufficiently accurate for epigenetic studies.
Ctr2 regulates biogenesis of a cleaved form of mammalian Ctr1 metal transporter lacking the copper- and cisplatin-binding ecto-domain
Authors: Öhrvik Helena , Nose Yasuhiro , Wood L. Kent , Kim Byung-Eun , Gleber Sophie-Charlotte , Ralle Martina , Thiele Dennis J.
Published: October 2013

Significance

Copper is essential for normal growth and development because it serves roles in catalysis, signaling, and structure. Cells acquire copper through the copper transporter 1 (Ctr1) protein, a copper transporter that localizes to the cell membrane and intracellular vesicles. Both copper and the anticancer drug cisplatin are imported by Ctr1 by virtue of an extracellular domain rich in metal-binding amino acids. In this report we demonstrate that a protein structurally related to Ctr1, called Ctr2, plays a role in the generation or stability of a truncated form of Ctr1 lacking a large portion of the extracellular domain. Retention of this domain in mice or cells lacking Ctr2 enhances copper and cisplatin uptake, thereby establishing Ctr2 as a regulator of Ctr1 function.
Keratins as the main component for the mechanical integrity of keratinocytes
Authors: Ramms Lena , Fabris Gloria , Windoffer Reinhard , Schwarz Nicole , Springer Ronald , Zhou Chen , Lazar Jaroslav , Stiefel Simone , Hersch Nils , Schnakenberg Uwe , Magin Thomas M. , Leube Rudolf E. , Merkel Rudolf , Hoffmann Bernd
Published: October 2013

Significance

For decades, researchers have been trying to unravel one of the key questions in cell biology regarding keratin intermediate filament function in protecting epithelial cells against mechanical stress. For many different reasons, however, this fundamental hypothesis was still unproven. Here we answer this pivotal question by the use of keratin KO cells lacking complete keratin gene clusters to result in total loss of keratin filaments. This lack significantly softens cells, reduces cell viscosity, and elevates plastic cell deformation on force application. Reexpression of single keratin genes facilitates biomechanical complementation of complete cluster loss. Our manuscript therefore makes a very strong case for the crucial contribution of keratins to cell mechanics, with far-reaching implications for epithelial pathophysiology.
Lipoatrophy and severe metabolic disturbance in mice with fat-specific deletion of PPARγ
Authors: Wang Fenfen , Mullican Shannon E. , DiSpirito Joanna R. , Peed Lindsey C. , Lazar Mitchell A.
Published: October 2013

Significance

Obesity, due to increased adipose (fat) tissue, predisposes to metabolic diseases, including diabetes. Thus, it is important to understand adipose development and function. Peroxisome proliferator-activated receptor gamma (PPARγ) is widely believed to be the master regulator of adipocyte biology. Surprisingly, however, previous studies attempting to delete the PPARγ gene specifically in mouse adipose tissue did not demonstrate a dramatic phenotype. By using newer methods, the present study reports that fat-specific loss of PPARγ causes dramatic loss of adipose tissue, severe insulin resistance and diabetes, fatty liver, and abnormalities of bone, skin, and mammary glands, all of which contain adipose tissue. We show that adipocyte PPARγ is required for normal fat development and metabolic function in vivo.
Electrolytic synthesis of aqueous aluminum nanoclusters and in situ characterization by femtosecond Raman spectroscopy and computations
Authors: Wang Wei , Liu Weimin , Chang I-Ya , Wills Lindsay A. , Zakharov Lev N. , Boettcher Shannon W. , Cheong Paul Ha-Yeon , Fang Chong , Keszler Douglas A.
Published: October 2013

Significance

The aqueous chemistry of Al has a large impact across the biosphere, hydrosphere, geosphere, and anthrosphere. Despite a century of study, aqueous Al chemistry and speciation are still not well understood because of the challenges of selectively isolating and synthesizing specific Al-containing aqueous clusters and of precisely characterizing those clusters. We report the atom- and step-economical electrolytic synthesis of aqueous Al clusters combined with improved femtosecond Raman spectroscopy and computations to elucidate the structures and formation pathways of aqueous clusters in situ. We demonstrate the unique power of this integrated platform by synthesizing and characterizing
flat
[Al
13
(μ
3
-OH)
6
(μ

2

-OH)
18
(H
2
O)
24
]
15+
clusters in water, which are versatile precursors for large-scale preparation of Al
2
O
3
thin films and nanoparticles for electronics, catalysis, and corrosion prevention.
Quantitative selection and parallel characterization of aptamers
Authors: Cho Minseon , Soo Oh Seung , Nie Jeff , Stewart Ron , Eisenstein Michael , Chambers James , Marth Jamey D. , Walker Faye , Thomson James A. , Soh H. Tom
Published: October 2013

Significance

The comprehensive functional mapping of the human proteome will require access to high-quality affinity reagents that specifically bind to their respective proteins with high affinities. Unfortunately, currently available antibodies can only target a small fraction of the proteome, and their affinity and specificity can vary considerably for each protein. Thus there is an urgent need for novel technologies capable of generating alternative, synthetic affinity reagents in a scalable and economical manner. Toward this end, we report a unique screening system (termed the “Quantitative Parallel Aptamer Selection System”) that can accelerate discovery of high-quality aptamer reagents by enabling simultaneous measurements of binding affinity (
K
d
) and specificity for thousands of aptamers in parallel.
Designing DNA-grafted particles that self-assemble into desired crystalline structures using the genetic algorithm
Authors: Srinivasan Babji , Vo Thi , Zhang Yugang , Gang Oleg , Kumar Sanat , Venkatasubramanian Venkat
Published: October 2013

Significance

The traditional, Edisonian method of research involves taking a system and examining its properties. A preferred alternative is to target a suite of properties and then design the most appropriate system in this context. Here we illustrate such a design approach for the self-assembly of colloids grafted with single-stranded DNA. When two types of colloids grafted with complementary ssDNA sequences are mixed, DNA hybridization can lead to the formation of ordered colloidal crystals. We use the genetic algorithm to design ssDNA-grafted particles that will assemble into a desired structure. Our methodology is easily generalizable, fast and highly selective, and not only accurately reproduces the parameters relevant to four currently realized crystals but also elucidates four currently unobserved structures.
Enhanced fatigue endurance of metallic glasses through a staircase-like fracture mechanism
Authors: Gludovatz Bernd , Demetriou Marios D. , Floyd Michael , Hohenwarter Anton , Johnson William L. , Ritchie Robert O.
Published: October 2013

Significance

We believe this article is of broad interest to the materials science and engineering community. Bulk-metallic glasses (BMGs) are currently considered candidate materials for numerous structural applications. A major limitation in their use as engineering material is the often poor and inconsistent fatigue behavior. Although recently developed BMG composites provide one solution to this problem, fatigue remains a main issue for monolithic metallic glasses. The authors report unexpectedly high fatigue resistance in a monolithic Pd-based glass arising from extensive shear-band plasticity, resulting in a very rough and periodic “staircase” crack trajectory. The research both reveals a unique mechanism in fatigue of a monolithic metallic glass and demonstrates that this mechanism mitigates previous limitations on its use as an engineering material.
An applied genre analysis of office hours consultations
Authors: Reinhardt Jonathon
Published: October 2013

This paper describes an examination of academic consultation discourse using an applied genre analytic approach (Bhatia 2002a) to inform English for academic purposes curriculum design and to contribute to interactional pragmatics and politeness research. The project employed a series of complementary genre and corpus-informed analyses, namely contextual (Tribble 2002), phase (Agar 1985), and interactional moves analysis (Swales 1990) focused on the use of framing (e.g. Goffman 1974), in conjunction with contrastive corpus analysis (Granger 1998). Data for the analyses originated in the office hours sub-corpus of MICASE (Simpson et al. 2002), and a spoken learner corpus of international teaching assistants in training (Reinhardt 2010). Results are interpreted using a model of directive language use in academic consultation discourse that considers appeals to choice and involvement as complementary rather than conflated. The genre of office hours emerges from the negotiated textualization of directive moves, framed around directive constructions using interactional politeness appeals.
Going the Distance: Memory and Control Processes in Active Dependency Construction
Authors: Wagers Matthew W. , Phillips Colin
Published: October 2013

Filler–gap dependencies make strong demands on working memory in language comprehension because they cannot always be immediately resolved. In a series of three reading-time studies, we test the idea that these demands can be decomposed into active maintenance processes and retrieval events. Results indicate that the fact that a displaced phrase exists and the identity of its basic syntactic category both immediately impact comprehension at potential gap sites. In contrast, specific lexical details of the displaced phrase show an immediate effect only for short dependencies and a much later effect for longer dependencies. We argue that coarse-grained information about the filler is actively maintained and is used to make phrase structure parsing decisions, whereas finer grained information is more quickly released from active maintenance and consequently has to be retrieved at the gap site.
Direction pathway analysis of large-scale proteomics data reveals novel features of the insulin action pathway
Authors: Yang Pengyi , Patrick Ellis , Tan Shi-Xiong , Fazakerley Daniel J. , Burchfield James , Gribben Christopher , Prior Matthew J. , James David E. , Hwa Yang Yee
Published: October 2013

Motivation: With the advancement of high-throughput techniques, large-scale profiling of biological systems with multiple experimental perturbations is becoming more prevalent. Pathway analysis incorporates prior biological knowledge to analyze genes/proteins in groups in a biological context. However, the hypotheses under investigation are often confined to a 1D space (i.e. up, down, either or mixed regulation). Here, we develop direction pathway analysis (DPA), which can be applied to test hypothesis in a high-dimensional space for identifying pathways that display distinct responses across multiple perturbations.

Results: Our DPA approach allows for the identification of pathways that display distinct responses across multiple perturbations. To demonstrate the utility and effectiveness, we evaluated DPA under various simulated scenarios and applied it to study insulin action in adipocytes. A major action of insulin in adipocytes is to regulate the movement of proteins from the interior to the cell surface membrane. Quantitative mass spectrometry-based proteomics was used to study this process on a large-scale. The combined dataset comprises four separate treatments. By applying DPA, we identified that several insulin responsive pathways in the plasma membrane trafficking are only partially dependent on the insulin-regulated kinase Akt. We subsequently validated our findings through targeted analysis of key proteins from these pathways using immunoblotting and live cell microscopy. Our results demonstrate that DPA can be applied to dissect pathway networks testing diverse hypotheses and integrating multiple experimental perturbations.

Availability and implementation: The R package ‘directPA’ is distributed from CRAN under GNU General Public License (GPL)-3 and can be downloaded from: http://cran.r-project.org/web/packages/directPA/index.html

Contact: jean.yang@sydney.edu.au

Supplementary Information:  Supplementary data are available at Bioinformatics online.
Governing multicultural populations and family life
Authors: Ali Suki
Published: October 2013

Shortly after coming to power in Britain, the Conservative–Liberal Democratic alliance placed family life at the heart of their political agenda, and set out their plans to reform adoption. The paper draws upon debates about the reforms and considers them in articulation with concerns about health of the nation expressed in political pronouncements on ‘broken Britain’ and the failures of ‘state multiculturalism’. The paper considers the debates about domestic (transracial) and intercountry adoption, and uses feminist postcolonial perspectives to argue that we can only understand what are expressed as national issues within a transnational and postcolonial framework which illuminate the processes of state and institutional race‐making. The paper analyses three key instances of biopower and governmentality in the adoption debates: the population, the normalizing family and the individual. The paper argues that we need to understand the reforms as part of a wider concern with the ‘problem’ of multicultural belonging, and that the interlocking discourses of nation, family and identities are crucial to the constitution and regulation of gendered, racialized subjects.