bluuebunny/crossref_metadata_2025 huggingface dataset:
Toward reading the sequence of short oligonucleotides from their retention factors obtained by means of hydrophilic interaction chromatography and ion‐interaction reversed‐phase liquid chromatography
Authors: Bittová Miroslava , Havliš Jan , Fuksová Hana , Vrbková Blanka , Trnková Libuše
Published: November 2012

Retention characteristics of selected synthetic 5′‐terminal phosphate absent penta‐nucleotides containing adenine, guanine, and thymine were studied in relation to their sequence by hydrophilic interaction chromatography and ion‐interaction reversed‐phase liquid chromatography. The organic solvent content, pH, and buffer concentration in mobile phases were evaluated as influential separation conditions. Data demonstrate that both compared chromatographic modes can be used to separate synthetic penta‐nucleotides according to their nucleotide composition. Moreover, reversed‐phase liquid chromatography allows separation according to their sequence. We have found a simple linear additive model to describe the retention order in both separation modes in regard to their sequence. In hydrophilic interaction chromatography, the retention behavior is controlled primarily by the hydrophilicity of involved nucleotides and minimally by their sequence position. For reversed‐phase liquid chromatography, the nucleotide hydrophobicity plays an important role in their retention properties and the influence of their location in sequence on the retention increases toward the center and decreases toward the termini. Our results show that the penta‐nucleotide sequence, and thus its spatial arrangement induced by the surrounding environment, is highly related to the retention properties, so it may be hypothetically used to read the sequence from the retention properties acquired under particular separation conditions.
Determination of three capsaicinoids in Capsicum annuum by pressurized liquid extraction combined with LC‐MS/MS
Authors: Liu Aili , Han Chao , Zhou Xiujin , Zhu Zhenou , Huang Fuzhen , Shen Yan
Published: November 2012

A new method based on pressurized liquid extraction followed by LC‐MS/MS analysis has been developed for the identification and quantification of three capsaicinoids (capsaicin, dihydrocapsaicin, and nordihydrocapsaicin) in extracts of Capsicum annuum. For the recovery of three capsaicinoids, the efficiency levels of ultrasonic‐assisted extraction, microwave‐assisted extraction, Soxhlet extraction, and pressurized liquid extraction were compared under different conditions. Pressurized liquid extraction resulted in higher yields. Pressurized liquid extractions were performed using methanol; temperature was set at 100°C and pressure at 1500 psi. LC analysis was performed on a Waters XBridge™ C18 column (150 × 2.1 mm, id 3.5 μm) eluted by a mobile phase of 0.1% formic acid and ACN. Data acquisition was carried out in multiple reaction monitoring transitions mode, monitoring two‐reaction monitoring transitions to ensure an accurate identification of target compounds in the samples. The proposed method is rapid, simple, and could be utilized for the routine analysis of three capsaicinoids in C. annuum samples.
Is Verbal Irony Special?
Authors: Bryant Gregory A.
Published: November 2012

The way we speak can reveal much about what we intend to communicate, but the words we use often only indirectly relate to the meanings we wish to convey. Verbal irony is a commonly studied form of indirect speech in which a speaker produces an explicit evaluative utterance that implicates an unstated, opposing evaluation. Producing and understanding ironic language, as well as many other types of indirect speech, requires the ability to recognize mental states in others, sometimes described as a capacity for metarepresentation. This article aims to connect common elements between the major theoretical approaches to verbal irony to recent psycholinguistic, developmental, and neuropsychological research demonstrating the necessity for metarepresentation in the effective use of verbal irony in social interaction. Here I will argue that verbal irony is one emergent, strategic possibility given the interface between people’s ability to infer mental states, and use language. Rather than think of ironic communication as a specialized cognitive ability, I will claim that it arises from the same set of abilities that underlie a wide range of inferential communicative behaviors.
Impact of Peptide Micropatterning on Endothelial Cell Actin Remodeling for Cell Alignment under Shear Stress
Authors: Chollet Céline , Bareille Reine , Rémy Murielle , Guignandon Alain , Bordenave Laurence , Laroche Gaetan , Durrieu Marie‐Christine
Published: November 2012

HSVEC behavior under physiological shear stress in vitro is investigated on PET surfaces micropatterned with both RGDS and WQPPRARI peptides. This technique allows (i) creating geometries on surface to guide cell orientation under shear stress and (ii) controlling surface chemical composition in order to modulate cell behavior. Under shear stress, endothelial cells adhere on patterned PET surfaces and present a more rapid orientation in flow direction in comparison to cells cultured on homogeneous surfaces. Micropatterned surfaces presenting a large surface area ratio of RGDS/WQPPRARI peptides induce fibrillar adhesion, while surfaces presenting an equal RGDS/WQPPRARI peptides surface area ratio preferentially induce focal adhesion.

magnified image
Structural Color and Iridescence in Transparent Sheared Cellulosic Films
Authors: Fernandes Susete N. , Geng Yong , Vignolini Silvia , Glover Beverley J. , Trindade Ana C. , Canejo João P. , Almeida Pedro L. , Brogueira Pedro , Godinho Maria H.
Published: November 2012

Shear transparent cellulose free‐standing thin films can develop iridescence similar to that found in petals of the tulip “Queen of the Night.” The iridescence of the film arises from the modulation of the surface into bands periodically spread perpendicular to the shear direction. Small amounts of nanocrystalline cellulose (NCC) rods in the precursor liquid‐crystalline solutions do not disturb the optical properties of the solutions but enhance the mechanical characteristics of the films and affects their iridescence. Smaller bands periodicity, not affected by the NCC rods, slightly deviated from the shear direction is also observed. NCCs are crucial to tune and understand the film's surface features formation. Our findings could lead to new materials for application in soft reflective screens and devices.
First Symposium on Poly(2‐oxazoline)s and Related Pseudo‐Polypeptide Structures
Authors: de la Rosa Victor R. , Bouten Petra J. M. , Hoogenboom Richard
Published: November 2012

The first symposium on poly(2‐oxazo‐line)s and related pseudo‐polypeptide structures was held as part of the 243rd American Chemical Society National Meeting in San Diego (CA) from the 27th to the 29th of March 2012. The scientists will gather again to discuss the progress in the field at the second symposium on poly(2‐oxazoline)s and pseudo‐polypeptides at the ACS National Meeting in San Francisco, to be held in August 2014.
Magnetization exchange observed in human skeletal muscle by non‐water‐suppressed proton magnetic resonance spectroscopy
Authors: MacMillan Erin L. , Boesch Chris , Kreis Roland
Published: November 2012

Many metabolites in the proton magnetic resonance spectrum undergo magnetization exchange with water, such as those in the downfield region (6.0–8.5 ppm) and the upfield peaks of creatine, which can be measured to reveal additional information about the molecular environment. In addition, these resonances are attenuated by conventional water suppression techniques complicating detection and quantification. To characterize these metabolites in human skeletal muscle in vivo at 3 T, metabolite cycled non‐water‐suppressed spectroscopy was used to conduct a water inversion transfer experiment in both the soleus and tibialis anterior muscles. Resulting median exchange‐independent T1 times for the creatine methylene resonances were 1.26 and 1.15 s, and for the methyl resonances were 1.57 and 1.74 s, for soleus and tibialis anterior muscles, respectively. Magnetization transfer rates from water to the creatine methylene resonances were 0.56 and 0.28 s−1, and for the methyl resonances were 0.39 and 0.30 s−1, with the soleus exhibiting faster transfer rates for both resonances, allowing speculation about possible influences of either muscle fibre orientation or muscle composition on the magnetization transfer process. These water magnetization transfer rates observed without water suppression are in good agreement with earlier reports that used either postexcitation water suppression in rats, or short CHESS sequences in human brain and skeletal muscle. Magn Reson Med, 70:916–924, 2013. © 2012 Wiley Periodicals, Inc.
In vivo blood T1 measurements at 1.5 T, 3 T, and 7 T
Authors: Zhang X. , Petersen E. T. , Ghariq E. , De Vis J. B. , Webb A. G. , Teeuwisse W. M. , Hendrikse J. , van Osch M. J. P.
Published: November 2012

The longitudinal relaxation time of blood is a crucial parameter for quantification of cerebral blood flow by arterial spin labeling and is one of the main determinants of the signal‐to‐noise ratio of the resulting perfusion maps. Whereas at low and medium magnetic field strengths (B0), its in vivo value is well established; at ultra‐high field, this is still uncertain. In this study, longitudinal relaxation time of blood in the sagittal sinus was measured at 1.5 T, 3 T, and 7 T. A nonselective inversion pulse preceding a Look‐Locker echo planar imaging sequence was performed to obtain the inversion recovery curve of venous blood. The results showed that longitudinal relaxation time of blood at 7 T was ∼ 2.1 s which translates to an anticipated 33% gain in the signal‐to‐noise ratio in arterial spin labeling experiments due to T1 relaxation alone compared with 3 T. In addition, the linear relationship between longitudinal relaxation time of blood and B0 was confirmed. Magn Reson Med, 70:1082–1086, 2013. © 2012 Wiley Periodicals, Inc.
Multigrid methods for cell‐centered discretizations on triangular meshes
Authors: Salinas P. , Rodrigo C. , Gaspar F. J. , Lisbona F. J.
Published: November 2012

This paper deals with the design of efficient multigrid methods for cell‐centered finite volume schemes on semi‐structured triangular grids. Appropriate novel smoothers are proposed for this type of discretizations, depending on the geometry of the grid. Because of the semi‐structured character of the mesh, on each structured patch, different smoothers can be considered. In this way, the multigrid method is constructed in a block‐wise form, and its global behavior will rely on the components on each block. Numerical experiments are presented to illustrate the good behavior of the proposed multigrid method. Copyright © 2012 John Wiley & Sons, Ltd.
Relational Aggression and Academic Performance in Elementary School
Authors: Risser Scott D.
Published: November 2012

To investigate the relationship between relational aggression and school performance, this study examined the relative and combined associations among relational aggression, overt aggression, and victimization and children's academic performance. Additionally this study examined the relative associations among relational and overt aggression and verbal and performance IQ. Participants in this study were a subset of the National Institute of Child Health and Human Development (NICHD) Study of Early Child Care and Youth Development. The study included 1,067 children (50% male) assessed during fourth and fifth grade. Results indicated that for girls, relational aggression was negatively associated with school performance, while statistically controlling for both victimization and overt aggression. For boys, overt aggression was negatively related with school performance. Additional results indicated that for both girls and boys, victimization was negatively associated with school performance.
Properties of trench defects in InGaN/GaN quantum well structures
Authors: Sahonta S.‐L. , Kappers M. J. , Zhu D. , Puchtler T. J. , Zhu T. , Bennett S. E. , Humphreys C. J. , Oliver R. A.
Published: November 2012

The structural and optical properties of trench defects, which are poorly understood yet commonly occurring defects observed on the surfaces of InGaN multiple quantum wells (MQW), are reported. These defects comprise near‐circular trenches which enclose areas of MQW which give rise to a red shift in peak photoluminescence emission and a change in cathodoluminescence intensity with respect to the surrounding material. Atomic force microscopy shows that the height of trench‐enclosed areas differs from that of the surrounding quantum well structure, and that trenches are unrelated to the commonly observed V‐defects in InGaN films, despite being occasionally intersected by them. Cross‐sectional electron microscopy analysis of trenches with raised centres suggests that the red shift in the observed cathodoluminescence peak emission may be due to the quantum wells being thicker in the trench‐enclosed regions than in the surrounding quantum well area. The mechanism of trench formation and its implication for the control of the emission properties of light‐emitting diodes is discussed.
Influence of defect characteristics on the nanoindentation response of a‐plane GaN thin films
Authors: Kavouras P. , Lotsari A. , Kehagias Th. , Georgakilas A. , Komninou Ph. , Dimitrakopoulos G. P.
Published: November 2012

a‐plane ($11{\bar {2}}0$) GaN thin films grown under various conditions on r‐plane sapphire by plasma‐assisted molecular beam epitaxy (PAMBE) were characterized by nanoindentation and transmission electron microscopy (TEM) techniques. It was found that the increase of the built‐in threading dislocation (TD) density induces an increase on the values of both the nanohardness (H) and the reduced elastic modulus (E*). Characteristic single ‘pop‐in’ discontinuities were detected on the loading segments of the load–unload cycle. The TDs appear to cause a decrease of the load for the onset of the pop‐in discontinuity. The dependence of the elastoplastic behaviour on the TD density is attributed to their sessile character, causing them to become obstacles for basal plane slip.
Surface characterization and radical decay studies of oxygen plasma‐treated PMMA films
Authors: Ozgen Ozge , Aksoy Eda Ayse , Hasirci Vasif , Hasirci Nesrin
Published: November 2012

Polymethylmethacrylate (PMMA) films were modified by RF oxygen plasma with various powers applied for different periods, and the effects of these parameters on the surface properties such as hydrophilicity, surface free energy (SFE), chemistry, and topography were investigated by water contact angle, goniometer, X‐ray photoelectron spectroscopy (XPS), and atomic force microscopy, and the types of the created free radicals and their decay were detected by electron spin resonance spectroscopy (ESR). SFE and contact angle results varied depending on the plasma parameters. Oxygen plasma treatment (100 W–30 min) enhanced the hydrophilicity of PMMA surface as shown by decreasing the water contact angle from 70° to 26°. XPS analysis showed the change in the amounts of the present functionalities as well as formation of new groups as free carbonyl and carbonate groups. The roughness of the surface increased considerably from ~2 nm to ~75 nm after 100 W–30 min oxygen plasma treatment. ESR analysis indicated the introduction of peroxy radicals by oxygen plasma treatment, and the intensity of the radicals increased with increasing the applied power. Significant decrease in radical concentration was observed especially for the samples treated with higher powers when the samples were kept under the atmospheric conditions. As a conclusion, RF plasma, causes changes in the chemical and physical properties of the materials depending on the applied parameters, and can be used for the creation of specific groups or radicals to link or immobilize active molecules onto the surface of a material. Copyright © 2012 John Wiley & Sons, Ltd.
A new linear model‐based approach for inferences about the mean area under the curve
Authors: Wilding Gregory E. , Chandrasekhar Rameela , Hutson Alan D.
Published: November 2012

Outcome versus time data are commonly encountered in biomedical and clinical research. A common strategy adopted in analyzing such longitudinal data is to condense the repeated measurements on each individual into a single summary statistic such as the area under the response versus time curve. Standard parametric or non‐parametric methods are then applied to perform inferences on the conditional area under the curve distribution. Disadvantages of this approach include the disregard of the within‐subject variation in the longitudinal profile. We propose a general linear model approach, accounting for the within‐subject variance, for estimation and hypothesis tests about the mean areas. Inferential properties of our approach are compared with those from standard methods of analysis using Monte Carlo simulation studies. The impact of missing data, within‐subject heterogeneity and homogeneity of variance, are also evaluated. A real working example is used to illustrate the methodology. It is seen that the proposed approach is associated with a significant power advantage over traditional methods, especially when missing data are encountered. Copyright © 2012 John Wiley & Sons, Ltd.
Comparing diagnostic tests: trials in people with discordant test results
Authors: Hooper R. , Díaz‐Ordaz K. , Takeda A. , Khan K.
Published: November 2012

Diagnostic tests are traditionally compared for accuracy against a gold standard but can also be compared prospectively in a trial. A conventional trial comparing two tests would randomize each participant to a testing strategy, but a more efficient alternative is to give both tests to all participants and follow up those with discordant results. Participants could be randomized before or after testing. The statistical analysis of such a trial has not previously been described. We investigated two estimates of the risk difference for a binary outcome: one based on analysing outcomes as if from a conventional trial and one combining estimates of different parameters in the manner of a decision analysis. We show that the trial estimate and decision analysis estimate are both unbiased and derive approximate formulae for their standard errors. By using the decision analysis estimate (but not the trial estimate), the same precision can be achieved by randomizing before testing as by randomizing after. To avoid destroying equipoise, and to allow consenting and randomizing to be carried out at the same visit, we recommend randomizing before testing. Giving both tests to all participants means fewer need to be recruited: in one example from the literature, the proposed design was nearly four times more efficient in this sense than a conventional trial design. Copyright © 2012 John Wiley & Sons, Ltd.
Bandwidth‐aware divisible task scheduling for cloud computing
Authors: Lin Weiwei , Liang Chen , Wang James Z. , Buyya Rajkumar
Published: November 2012

Task scheduling is a fundamental issue in achieving high efficiency in cloud computing. However, it is a big challenge for efficient scheduling algorithm design and implementation (as general scheduling problem is NP‐complete). Most existing task‐scheduling methods of cloud computing only consider task resource requirements for CPU and memory, without considering bandwidth requirements. In order to obtain better performance, in this paper, we propose a bandwidth‐aware algorithm for divisible task scheduling in cloud‐computing environments. A nonlinear programming model for the divisible task‐scheduling problem under the bounded multi‐port model is presented. By solving this model, the optimized allocation scheme that determines proper number of tasks assigned to each virtual resource node is obtained. On the basis of the optimized allocation scheme, a heuristic algorithm for divisible load scheduling, called bandwidth‐aware task‐scheduling (BATS) algorithm, is proposed. The performance of algorithm is evaluated using CloudSim toolkit. Experimental result shows that, compared with the fair‐based task‐scheduling algorithm, the bandwidth‐only task‐scheduling algorithm, and the computation‐only task‐scheduling algorithm, the proposed algorithm (BATS) has better performance. Copyright © 2012 John Wiley & Sons, Ltd.
Transcription Elongation Factor Tcea3 Regulates the Pluripotent Differentiation Potential of Mouse Embryonic Stem Cells Via the Lefty1-Nodal-Smad2 Pathway
Authors: Park Kyung-Soon , Cha Young , Kim Chun-Hyung , Ahn Hee-Jin , Kim Dohoon , Ko Sanghyeok , Kim Kyeoung-Hwa , Chang Mi-Yoon , Ko Jong-Hyun , Noh Yoo-Sun , Han Yong-Mahn , Kim Jonghwan , Song Jihwan , Kim Jin Young , Tesar Paul J. , Lanza Robert , Lee Kyung-Ah , Kim Kwang-Soo
Published: November 2012

Self-renewal and pluripotency are hallmark properties of pluripotent stem cells, including embryonic stem cells (ESCs) and iPS cells. Previous studies revealed the ESC-specific core transcription circuitry and showed that these core factors (e.g., Oct3/4, Sox2, and Nanog) regulate not only self-renewal but also pluripotent differentiation. However, it remains elusive how these two cell states are regulated and balanced during in vitro replication and differentiation. Here, we report that the transcription elongation factor Tcea3 is highly enriched in mouse ESCs (mESCs) and plays important roles in regulating the differentiation. Strikingly, altering Tcea3 expression in mESCs did not affect self-renewal under nondifferentiating condition; however, upon exposure to differentiating cues, its overexpression impaired in vitro differentiation capacity, and its knockdown biased differentiation toward mesodermal and endodermal fates. Furthermore, we identified Lefty1 as a downstream target of Tcea3 and showed that the Tcea3-Lefty1-Nodal-Smad2 pathway is an innate program critically regulating cell fate choices between self-replication and differentiation commitment. Together, we propose that Tcea3 critically regulates pluripotent differentiation of mESCs as a molecular rheostat of Nodal-Smad2/3 signaling.
Concise Review: Bone Marrow Meets Blastocyst: Lessons from an Unlikely Encounter
Authors: Binas Bert , Verfaillie Catherine M.
Published: November 2012

This article discusses the implications of the recent discovery that rat bone marrow-derived multipotent adult progenitor cells (rMAPCs), a cell type with broad somatic differentiation potential but of uncertain lineage identity, are similar to rat blastocyst-derived extraembryonic endoderm precursor (rXENP) cells, which appear to represent the committed extraembryonic endoderm precursor of the blastocyst. It was found that under rMAPC culture conditions, rXENP cells can be homogeneously cultured and similar cells, named rat hypoblast stem cells (rHypoSCs), can be derived from rat blastocysts more rapidly and directly. The detailed comparison of rHypoSCs, rXENP cells, and rMAPCs revealed highly similar gene expression profiles and developmental potentials. The significance of these findings for embryology, stem cell biology, and medicine is discussed. Specifically, the results assign a lineage identity to rMAPCs, indicate that rMAPCs originated by environmental reprogramming, and imply that HypoSCs, XENP cells, and MAPCs possess lineage plasticity. The MAPC-HypoSC relation also strengthens the consistency of rat and mouse embryology and consequently the idea that HypoSCs represent the committed extraembryonic endoderm precursor of the blastocyst. On this basis, it is argued that the direct comparison of HypoSCs (now available in pure form) with embryonic stem cells will be highly useful for the understanding of pluripotency and plasticity. Finally, the new findings suggest an explanation for an obscure observation on stem cell-induced transplantation tolerance. Thus, the HypoSC/XENP/MAPC phenotype provides a unique but broadly instructive model with which to study stem cell plasticity, reprogramming, and transplantation tolerance, all central themes in regenerative medicine. STEM CELLS2013;31:620–626
Differentially Activated Macrophages Orchestrate Myogenic Precursor Cell Fate During Human Skeletal Muscle Regeneration
Authors: Saclier Marielle , Yacoub-Youssef Houda , Mackey Abigail L. , Arnold Ludovic , Ardjoune Hamida , Magnan Mélanie , Sailhan Frédéric , Chelly Jamel , Pavlath Grace K. , Mounier Rémi , Kjaer Michael , Chazaud Bénédicte
Published: November 2012

Macrophages (MPs) exert either beneficial or deleterious effects on tissue repair, depending on their activation/polarization state. They are crucial for adult skeletal muscle repair, notably by acting on myogenic precursor cells. However, these interactions have not been fully characterized. Here, we explored both in vitro and in vivo, in human, the interactions of differentially activated MPs with myogenic precursor cells (MPCs) during adult myogenesis and skeletal muscle regeneration. We showed in vitro that through the differential secretion of cytokines and growth factors, proinflammatory MPs inhibited MPC fusion while anti-inflammatory MPs strongly promoted MPC differentiation by increasing their commitment into differentiated myocytes and the formation of mature myotubes. Furthermore, the in vivo time course of expression of myogenic and MP markers was studied in regenerating human healthy muscle after damage. We observed that regenerating areas containing proliferating MPCs were preferentially associated with MPs expressing proinflammatory markers. In the same muscle, regenerating areas containing differentiating myogenin-positive MPCs were preferentially coupled to MPs harboring anti-inflammatory markers. These data demonstrate for the first time in human that MPs sequentially orchestrate adult myogenesis during regeneration of damaged skeletal muscle. These results support the emerging concept that inflammation, through MP activation, controls stem cell fate and coordinates tissue repair.
Molecular dynamics simulations and statistical coupling analysis reveal functional coevolution network of oncogenic mutations in the CDKN2A–CDK6 complex
Authors: Wang Jingwen , Zhao Yuqi , Wang Yanjie , Huang Jingfei
Published: November 2012

Coevolution between proteins is crucial for understanding protein–protein interaction. Simultaneous changes allow a protein complex to maintain its overall structural–functional integrity. In this study, we combined statistical coupling analysis (SCA) and molecular dynamics simulations on the CDK6–CDKN2A protein complex to evaluate coevolution between proteins. We reconstructed an inter‐protein residue coevolution network, consisting of 37 residues and 37 interactions. It shows that most of the coevolved residue pairs are spatially proximal. When the mutations happened, the stable local structures were broken up and thus the protein interaction was decreased or inhibited, with a following increased risk of melanoma. The identification of inter‐protein coevolved residues in the CDK6–CDKN2A complex can be helpful for designing protein engineering experiments.
Nuclear localization of clathrin involves a labile helix outside the trimerization domain
Authors: Ybe Joel A. , Fontaine Sarah N. , Stone Todd , Nix Jay , Lin Xiaoyan , Mishra Sanjay
Published: November 2012

Clathrin is a trimeric protein involved in receptor‐mediated‐endocytosis, but can function as a non‐trimer outside of endocytosis. We have discovered that the subcellular distribution of a clathrin cysteine mutant we previously studied is altered and a proportion is also localized to nuclear spaces. MALS shows C1573A hub is a mixture of trimer‐like and detrimerized molecules. The X‐ray structure of the trimerization domain reveals that without light chains, a helix harboring cysteine‐1573 is reoriented. We propose clathrin has a detrimerization switch, which suggests clathrin topology can be altered naturally for new functions.
The thioredoxin reductase‐thioredoxin system is involved in the entry of tetanus and botulinum neurotoxins in the cytosol of nerve terminals
Authors: Pirazzini Marco , Bordin Fulvio , Rossetto Ornella , Shone Clifford C. , Binz Thomas , Montecucco Cesare
Published: November 2012

Tetanus and botulinum neurotoxins cause paralysis by cleaving SNARE proteins within the cytosol of nerve terminals. They are endocytosed inside acidic vesicles and the pH gradient across the membrane drives the translocation of their metalloprotease L domain in the cytosol. This domain is linked to the rest of the molecule by a single interchain disulfide bridge that has to be reduced on the cytosolic side of the membrane to free its enzymatic activity. By using specific inhibitors of the various cytosolic protein disulfides reducing systems, we show here that the NADPH‐thioredoxin reductase‐thioredoxin redox system is the main responsible for this disulfide reduction. In addition, we indicate auranofin, as a possible basis for the design of novel inhibitors of these neurotoxins.
Vascular disease and dementias: Paradigm shifts to drive research in new directions
Authors: Kling Mitchel A. , Trojanowski John Q. , Wolk David A. , Lee Virginia M.Y. , Arnold Steven E.
Published: November 2012

Vascular disease was once considered the principal cause of aging‐related dementia. More recently, however, research emphasis has shifted to studies of progressive neurodegenerative disease processes, such as those giving rise to neuritic plaques, neurofibrillary tangles, and Lewy bodies. Although these studies have led to critical insights and potential therapeutic strategies, interest in the role of systemic and cerebrovascular disease mechanisms waned and has received relatively less attention and research support. Recent studies suggest that vascular disease mechanisms play an important role in the risk for aging‐related cognitive decline and disorders. Vascular disease frequently coexists with cognitive decline in aging individuals, shares many risk factors with dementias considered to be of the “Alzheimer type,” and is observed more frequently than expected in postmortem material from individuals manifesting “specific” disease stigmata, such as abundant plaques and tangles. Considerable difficulties have emerged in attempting to classify dementias as being related to vascular versus neurodegenerative causes, and several systems of criteria have been used. Despite multiple attempts, a lack of consensus remains regarding the optimal means of incorporating vascular disease into clinical diagnostic, neurocognitive, or neuropathologic classification schemes for dementias. We propose here an integrative, rather than a strictly taxonomic, approach to the study and elucidation of how vascular disease mechanisms contribute to the development of dementias. We argue that, instead of discriminating between, for example, “Alzheimer's disease,” “vascular dementia,” and other diseases, there is a greater need to focus clinical and research efforts on elucidating specific pathophysiologic mechanisms that contribute to dementia phenotypes and neuropathologic outcomes. We outline a multitiered strategy, beginning with clinical and public health interventions that can be implemented immediately, enhancements to ongoing longitudinal studies to increase their informative value, and new initiatives to capitalize on recent advances in systems biology and network medicine. This strategy will require funding from multiple public and private sources to support collaborative and interdisciplinary research efforts to take full advantage of these opportunities and realize their societal benefits.
Complete versus culprit‐only revascularization during primary percutaneous coronary intervention in ST‐elevation myocardial infarction patients with multivessel disease: A meta‐analysis
Authors: Lu Cong , Huang Hao , Li Jing , Zhao Jianxun , Zhang Qing , Zeng Zhi , Chen Yucheng
Published: November 2012

Complete versus culprit‐only revascularization in acute ST‐elevation myocardial infarction (STEMI) patients with multivessel disease is controversial. Current guidelines recommend treatment of the culprit artery alone during the primary procedure. However, with improvements in stent technique and with the use of new antiplatelet drugs (GP IIb/IIIa inhibitors), complete revascularization (CR) at an early stage is attracting increasing attention. We conducted an English language search on Medline (PubMed database), Embase, and the Cochrane databases between January 1966 and January 2011, as well as a search on the China National Knowledge Internet (1979–January 2011), and the Chinese Biomedical Literature Database (1978–January 2011). Randomized controlled trials (RCTs) or non‐RCTs that compared the two strategies in patients with STEMI and multivessel disease (MVD) during primary percutaneous coronary intervention (PCI) were included. Thirteen articles were selected, 8240 patients in the CR group and 51,998 in the culprit‐only revascularization group. CR was associated with an increased short‐term mortality [odds ratio (OR) = 1.39, 95% confidence interval (CI) = (1.26, 1.53)], a long‐term mortality [OR = 1.35, 95% CI = (1.09, 1.67)], and an increased risk of renal failure [OR (95% CI) = 1.24 (1.11, 1.38)] in patients with STEMI and MVD at the primary procedure. In addition, CR did not reduce the rate of short‐term major adverse cardiac events [OR (95% CI) = 1.52 (0.88, 2.61)] and remyocardial infarction [OR = 0.57, 95% CI = (0.25, 1.29)]. However, CR was associated with a marked reduction in the rate of revascularization [OR = 0.45, 95% CI = (0.27, 0.74)]. This analysis of current available data demonstrates that CR during primary PCI can put those patients with STEMI and MVD at risk. To clarify this issue, large RCTs are needed.
Leptin increases HER2 protein levels through a STAT3‐mediated up‐regulation of Hsp90 in breast cancer cells
Authors: Giordano Cinzia , Vizza Donatella , Panza Salvatore , Barone Ines , Bonofiglio Daniela , Lanzino Marilena , Sisci Diego , De Amicis Francesca , Fuqua Suzanne A.W. , Catalano Stefania , Andò Sebastiano
Published: November 2012

Obesity condition confers risks to breast cancer development and progression, and several reports indicate that the adipokine leptin, whose synthesis and plasma levels increase with obesity, might play an important role in modulating breast cancer cell phenotype. Functional crosstalk occurring between leptin and different signaling molecules contribute to breast carcinogenesis.

In this study, we show, in different human breast cancer cell lines, that leptin enhanced the expression of a chaperone protein Hsp90 resulting in increased HER2 protein levels. Silencing of Hsp90 gene expression by RNA interference abrogated leptin‐mediated HER2 up‐regulation. Leptin effects were dependent on JAK2/STAT3 activation, since inhibition of this signaling cascade by AG490 or ectopic expression of a STAT3 dominant negative abrogated leptin‐induced HER2 and Hsp90 expressions. Functional experiments showed that leptin treatment significantly up‐regulated human Hsp90 promoter activity. This occurred through an enhanced STAT3 transcription factor binding to its specific responsive element located in the Hsp90 promoter region as revealed by electrophoretic mobility shift assay and chromatin immunoprecipitation assay. Analysis of HER2, Akt and MAPK phosphorylation levels revealed that leptin treatment amplified the responsiveness of breast cancer cells to growth factor stimulation. Furthermore, we found that long‐term leptin exposure reduced sensitivity of breast cancer cells to the antiestrogen tamoxifen. In the same experimental conditions, the combined treatment of tamoxifen with the Hsp90 inhibitor 17‐AAG completely abrogated leptin‐induced anchorage‐independent breast cancer cell growth.

In conclusion, our results highlight, for the first time, the ability of the adipocyte‐secreted factor leptin to modulate Hsp90/HER2 expressions in breast cancer cells providing novel insights into the molecular mechanism linking obesity to breast cancer growth and progression.
Hip Fracture−Related Pain Strongly Influences Functional Performance of Patients With an Intertrochanteric Fracture Upon Discharge From the Hospital
Authors: Kristensen Morten Tange
Published: November 2012

Objective

To examine whether functional performance upon hospital discharge is influenced by pain in the region of the hip fracture or related to the fracture type.

Design

Prospective observational study.

Setting

A 20‐bed orthopedic hip fracture unit.

Patients

Fifty‐five cognitively intact patients (20 men and 35 women; ages 75.8 ± 10 years), 33 with a cervical hip fracture and 22 with an intertrochanteric hip fracture, all of whom were allowed to bear full weight after surgery.

Methods

All patients were evaluated upon discharge from the hospital to their own homes at a mean of 10 ± 6 days after surgery.

Main Outcome Measurements

The Timed Up & Go (TUG) test, supervised by a physical therapist, was used to evaluate functional performance, and a 5‐point verbal ranking scale (0 = no pain to 4 = intolerable pain) was used to evaluate pain.

Results

Patients took an average of 22.7 ± 11.7 seconds to perform the TUG. No significant differences were observed in baseline characteristics or pain medication given for patients with a cervical versus an intertrochanteric fracture (P ≥ .22), but patients with an intertrochanteric fracture presented more often with moderate to severe pain during testing (P < .001), with associated poorer performances on the TUG test (29.4 ± 12.8 seconds versus 18.3 ± 8.5 seconds). Univariate analysis showed that TUG scores were associated with age, prefracture function evaluated by the New Mobility Score, fracture type, day of TUG performance, and pain intensity. Multivariate linear regression analyses (fracture type not included) showed that only greater age (B = 0.34), low prefracture function (B = 7.9), and experiencing moderate to severe pain (B = 8.7) were independently associated with having a poorer TUG score.

Conclusions

Hip fracture−related pain primarily compromises the functional performance of patients with an intertrochanteric hip fracture upon discharge from hospital. Physical therapists should be involved in new and optimized fracture‐type stratified pain management strategies.
Democracy Prevention
Authors: Brownlee Jason
Published: November 2012

When a popular revolt forced long-ruling Egyptian President Hosni Mubarak to resign on February 11, 2011, US President Barack Obama hailed the victory of peaceful demonstrators in the heart of the Arab World. But Washington was late to endorse democracy - for decades the United States favored Egypt's rulers over its people. Since 1979, the United States had provided the Egyptian regime with more than $60 billion in aid and immeasurable political support to secure its main interests in the region: Israeli security and strong relations with Persian Gulf oil producers. During the Egyptian uprising, the White House did not promote popular sovereignty but instead backed an 'orderly transition' to one of Mubarak's cronies. Even after protesters derailed that plan, the anti-democratic US-Egyptian alliance continued. Using untapped primary materials, this book helps explain why authoritarianism has persisted in Egypt with American support, even as policy makers claim to encourage democratic change.
Max Weber in Politics and Social Thought
Authors: Derman Joshua
Published: November 2012

Max Weber is widely regarded as one of the foundational thinkers of the twentieth century. But how did this reclusive German scholar manage to leave such an indelible mark on modern political and social thought? Max Weber in Politics and Social Thought is the first comprehensive account of Weber's wide-ranging impact on both German and American intellectuals. Drawing on a wide range of sources, Joshua Derman illuminates what Weber meant to contemporaries in the Weimar Republic and Nazi Germany and analyzes why they reached for his concepts to articulate such widely divergent understandings of modern life. The book also accounts for the transformations that Weber's concepts underwent at the hands of émigré and American scholars, and in doing so, elucidates one of the major intellectual movements of the mid-twentieth century: the transatlantic migration of German thought.
Declaring War
Authors: Hallett Brien
Published: November 2012

Declaring War directly challenges the 200-year-old belief that Congress can and should declare war. By offering a detailed analysis of the declarations of 1812, 1898 and the War Powers Resolution of 1973, the book demonstrates the extent of the organizational and moral incapacity of Congress to declare war. It invokes Carl von Clausewitz's dictum that 'war is policy' to explain why declarations of war are an integral part of war and proposes two possible remedies - a constitutional amendment or, alternatively, a significant re-organization of Congress. It offers a comprehensive historical, legal, constitutional, moral and philosophical analysis of why Congress has failed to check an imperial presidency. The book draws on Roman history and international law to clarify the form, function and language of declarations of war and John Austin's speech act theory.
Science, Democracy, and the American University
Authors: Jewett Andrew
Published: November 2012

This book reinterprets the rise of the natural and social sciences as sources of political authority in modern America. Andrew Jewett demonstrates the remarkable persistence of a belief that the scientific enterprise carried with it a set of ethical values capable of grounding a democratic culture - a political function widely assigned to religion. The book traces the shifting formulations of this belief from the creation of the research universities in the Civil War era to the early Cold War years. It examines hundreds of leading scholars who viewed science not merely as a source of technical knowledge, but also as a resource for fostering cultural change. This vision generated surprisingly nuanced portraits of science in the years before the military-industrial complex and has much to teach us today about the relationship between science and democracy.
Realism in the Twentieth-Century Indian Novel
Authors: Anjaria Ulka
Published: November 2012

Early twentieth-century Indian novels often depict the harsh material conditions of life under British colonial rule. Even so, these 'realist' novels are profoundly imaginative. In this study, Ulka Anjaria challenges the distinction between early twentieth-century social realism and modern-day magical realism, arguing that realism in the colony functioned as a mode of experimentation and aesthetic innovation – not merely as mimesis of the 'real world'. By examining novels from the 1930s across several Indian languages, Anjaria reveals how Indian authors used realist techniques to imagine alternate worlds, to invent new subjectivities and relationships with the Indian nation and to question some of the most entrenched values of modernity. Addressing issues of colonialism, Indian nationalism, the rise of Gandhi, religion and politics, and the role of literature in society, Anjaria's careful analysis will complement graduate study and research in English literature, South Asian studies and postcolonial studies.
SBA and MTF MCQs for the Final FRCA
Authors: Nickells James , Walton Benjamin ,   FRCAQ.COM Writers Group, Bristol National Health Service Trust
Published: November 2012

Preparing for the Final FRCA? Wondering what to expect of the SBA questions? Help is at hand. This practical book contains 60 single best answer and 120 multiple true/false questions to help you revise for the Final FRCA MCQ exam. Each question is accompanied by detailed explanations, giving additional information on each topic to enhance revision. SBA and MTF MCQs for the Final FRCA may be used both for examination practice and as a source of knowledge on many of the key topics in the syllabus. A helpful introductory section gives practical advice on how to approach revision and sitting the exam. From the writing team behind the FRCAQ.com website (www.frcaq.com), an outstanding exam preparation source for both the Primary and Final FRCA, this book provides challenging questions and well researched explanations to help you through the Final FRCA MCQ paper. An invaluable tool for your MCQ exam preparation.
Evaluating the Impact of Training Health Professionals to Deliver Brief Motivational and Skills-Based Interventions for Cannabis Use Disorder
Authors: Alperstein Dion , Copeland Jan
Published: November 2012

Background: While there is considerable evidence that brief motivational and skills-based interventions for substance use are effective, little is known regarding the transfer of knowledge from research to practice. This study aims to evaluate the effectiveness of two half-day didactic clinical training workshops for allied health workers, which did not incorporate feedback or supervision, via independent follow-up three months post training.

Methods: In total, 1322 participants attended either or both of the evidence-based treatment workshops run by the National Cannabis Prevention and Information Centre. Of those participants, 495 (37%) completed an online follow-up evaluation three months later regarding their use of the newly learnt intervention(s).

Results: At follow-up, 270 (54.5%) participants had an opportunity to use the skills and 144 (53.3%) of those participants reported having used the clinical skills taught in the workshop. Of those who used one of the interventions, 90 (62.5%) participants reported their clients had reduced or quit their cannabis use. Furthermore, 43 (30%) of these participants had attempted to train others in the workplace in the techniques learnt in the workshop.

Conclusion: Even a half-day didactic clinical training workshop on evidence-based brief cognitive–behavioural techniques delivered to clinicians working in the field can improve knowledge and confidence among clinicians and outcomes among their clients with cannabis use related problems.
THE COMPLEXITY OF RIEMANN SURFACES AND THE HURWITZ EXISTENCE PROBLEM
Authors: CRUZ-COTA ALDO-HILARIO , RAMIREZ-ROSAS TERESITA
Published: November 2012

Thecomplexityof a branched cover of a Riemann surfaceMto the Riemann sphereS2is defined as its degree times the hyperbolic area of the complement of its branching set inS2. ThecomplexityofMis defined as the infimum of the complexities of all branched covers ofMtoS2. We prove that ifMis a connected, closed, orientable Riemann surface of genusg≥1, then its complexity equals 2π(mmin+2g−2) , wheremminis the minimum total length of a branch datum realisable by a branched coverp:M→S2.
ON THE ORDER OF ARC-STABILISERS IN ARC-TRANSITIVE GRAPHS, II
Authors: VERRET GABRIEL
Published: November 2012

Let $\Gamma $ be a $G$-vertex-transitive graph and let $(u,v)$ be an arc of $\Gamma $. It is known that if the local action $G_v^{\Gamma (v)}$ (the permutation group induced by $G_v$ on $\Gamma (v)$) is permutation isomorphic to the dihedral group of degree four, then either $|G_{uv}|$ is ‘small’ with respect to the order of $\Gamma $ or $\Gamma $is one of a family of well-understood graphs. In this paper, we generalise this result to a wider class of local actions.
P-SPACES AND THE VOLTERRA PROPERTY
Authors: SPADARO SANTI
Published: November 2012

We study the relationship between generalisations ofP-spaces and Volterra (weakly Volterra) spaces, that is, spaces where every two denseGδhave dense (nonempty) intersection. In particular, we prove that every dense and every open, but not every closed subspace of an almostP-space is Volterra and that there are Tychonoff nonweakly Volterra weakP-spaces. These results should be compared with the fact that everyP-space is hereditarily Volterra. As a byproduct we obtain an example of a hereditarily Volterra space and a hereditarily Baire space whose product is not weakly Volterra. We also show an example of a Hausdorff space which contains a nonweakly Volterra subspace and is both a weakP-space and an almostP-space.