bluuebunny/crossref_metadata_2025 huggingface dataset:
Critical role of RAGE in lung physiology and tumorigenesis: a potential target of therapeutic intervention?
Authors: Marinakis Evangelos , Bagkos Georgios , Piperi Christina , Roussou Paraskevi , Diamanti-Kandarakis Evanthia
Published: October 2013

Lung cancer is one of the most common malignancies in the world and one of the leading causes of death from cancer. In the search for molecules that may be involved in lung tumor induction and progression, the receptor of advanced glycation end products (RAGE) comes across as a critical regulator of lung physiology. RAGE is a multiligand receptor that presents a differential expression pattern in lung epithelial cells compared to other cell types being gradually increased from fetal to birth and adult life. Under stress conditions, RAGE expression and activation are rapidly elevated resulting in chronic inflammation, which, in turn, in many instances, promotes epithelial cell malignant transformation. RAGE overexpression in normal lung alveolar type I epithelial cells is followed by rapid downregulation upon malignant transformation, being associated with increased aggressiveness. This is a striking paradox, since in every other cell type the pattern of RAGE expression follows the opposite direction, suggesting the involvement of RAGE in the well-functioning of lung cells. Additionally, RAGE has been attributed with the role of adhesion molecule, since it can stabilize mature alveolar epithelial cells to their substrate (basal lamina) by interacting electrostatically with other molecules. However, the reduction of RAGE observed in lung tumorigenesis interrupts cell-to-cell and cell-to-substrate communication, which is a critical step for cancer cell induction, progression and migration. This review addresses the differential properties of RAGE in lung physiology and carcinogenesis, providing evidence of therapeutic possibilities.
Prediction of the influence of processing parameters on synthesis of Al2024-B4C composite powders in a planetary mill using an artificial neural network
Authors: Varol Temel , Canakci Aykut , Ozsahin Sukru
Published: October 2013

In this study, an artificial neural network approach was employed to predict the effect of B4C size, B4C content, and milling time on the particle size and particle hardness of Al2024-B4C composite powders. Al2024-B4C powder mixtures with various reinforcement weight percentages (5%, 10%, and 20% B4C), reinforcement size (49 and 5 μm), and milling times (0–10 h) were prepared by mechanical alloying process. The properties of the composite powders were analyzed using a laser particle size analyzer for the particle size and a microhardness tester for the powder microhardness. The three input parameters in the proposed artificial neural network (ANN) were the reinforcement size, reinforcement ratio, and milling time. Particle size and particle hardness of the composite powders were the outputs obtained from the proposed ANN. The mean absolute percentage error for the predicted values did not exceed 4.289% for the best prediction model. This model can be used for predicting properties of Al2024-B4C composite powders produced with different reinforcement size, reinforcement ratio, and milling times.
Rapid Functional Reorganization in Human Cortex Following Neural Perturbation
Authors: Zanto Theodore P. , Chadick James Z. , Satris Gabriela , Gazzaley Adam
Published: October 2013

Despite the human brain's ability to rapidly reorganize neuronal activity patterns in response to interactions with the environment (e.g., learning), it remains unclear whether compensatory mechanisms occur, on a similar time scale, in response to exogenous cortical perturbations. To investigate this, we disrupted normal neural function via repetitive transcranial magnetic stimulation and assessed, using fMRI, activity changes associated with performance on a working memory task. Although transcranial magnetic stimulation disrupted neural activity in task-related brain regions, performance was not affected. Critically, another brain region not previously engaged by the task was recruited to uphold memory performance. Thus, functional reorganization of cortical activity can occur within minutes of neural disruption to maintain cognitive abilities.
NaV1.1 Channels in Axon Initial Segments of Bipolar Cells Augment Input to Magnocellular Visual Pathways in the Primate Retina
Authors: Puthussery Theresa , Venkataramani Sowmya , Gayet-Primo Jacqueline , Smith Robert G. , Taylor W. Rowland
Published: October 2013

In the primate visual system, the ganglion cells of the magnocellular pathway underlie motion and flicker detection and are relatively transient, while the more sustained ganglion cells of the parvocellular pathway have comparatively lower temporal resolution, but encode higher spatial frequencies. Although it is presumed that functional differences in bipolar cells contribute to the tuning of the two pathways, the properties of the relevant bipolar cells have not yet been examined in detail. Here, by making patch-clamp recordings in acute slices of macaque retina, we show that the bipolar cells within the magnocellular pathway, but not the parvocellular pathway, exhibit voltage-gated sodium (NaV), T-type calcium (CaV), and hyperpolarization-activated, cyclic nucleotide-gated (HCN) currents, and can generate action potentials. Using immunohistochemistry in macaque and human retinae, we show that NaV1.1 is concentrated in an axon initial segment (AIS)-like region of magnocellular pathway bipolar cells, a specialization not seen in transient bipolar cells of other vertebrates. In contrast, CaV3.1 channels were localized to the somatodendritic compartment and proximal axon, but were excluded from the AIS, while HCN1 channels were concentrated in the axon terminal boutons. Simulations using a compartmental model reproduced physiological results and indicate that magnocellular pathway bipolar cells initiate spikes in the AIS. Finally, we demonstrate that NaVchannels in bipolar cells augment excitatory input to parasol ganglion cells of the magnocellular pathway. Overall, the results demonstrate that selective expression of voltage-gated channels contributes to the establishment of parallel processing in the major visual pathways of the primate retina.
Interactions between White Matter Asymmetry and Language during Neurodevelopment
Authors: O'Muircheartaigh Jonathan , Dean Douglas C. , Dirks Holly , Waskiewicz Nicole , Lehman Katie , Jerskey Beth A. , Deoni Sean C.L.
Published: October 2013

The human brain is asymmetric in gross structure as well as functional organization. However, the developmental basis and trajectory of this asymmetry is unclear, and its relationship(s) to functional and cognitive development, especially language, remain to be fully elucidated. During infancy and early childhood, in concert with cortical gray matter growth, underlying axonal bundles become progressively myelinated. This myelination is critical for efficient and coherent interneuronal communication and, as revealed in animal studies, the degree of myelination changes in response to environment and neuronal activity. Using a novel quantitative magnetic resonance imaging method to investigate myelin contentin vivoin human infants and young children, we investigated gross asymmetry of myelin in a large cohort of 108 typically developing children between 1 and 6 years of age, hypothesizing that asymmetry would predict language abilities in this cohort. While asymmetry of myelin content was evident in multiple cortical and subcortical regions, language ability was predicted only by leftward asymmetry of caudate and frontal cortex myelin content and rightward asymmetry in the extreme capsule. Importantly, the influence of this asymmetry was found to change with age, suggesting an age-specific influence of structure and myelin on language function. The relationship between language ability and asymmetry of myelin stabilized at ∼4 years, indicating anatomical evidence for a critical time during development before which environmental influence on cognition may be greatest.
Plant Sterols the Better Cholesterol in Alzheimer's Disease? A Mechanistical Study
Authors: Burg Verena K. , Grimm Heike S. , Rothhaar Tatjana L. , Grösgen Sven , Hundsdörfer Benjamin , Haupenthal Viola J. , Zimmer Valerie C. , Mett Janine , Weingärtner Oliver , Laufs Ulrich , Broersen Laus M. , Tanila Heikki , Vanmierlo Tim , Lütjohann Dieter , Hartmann Tobias , Grimm Marcus O.W.
Published: October 2013

Amyloid-β (Aβ), major constituent of senile plaques in Alzheimer's disease (AD), is generated by proteolytic processing of the amyloid precursor protein (APP) by β- and γ-secretase. Several lipids, especially cholesterol, are associated with AD. Phytosterols are naturally occurring cholesterol plant equivalents, recently been shown to cross the blood–brain-barrier accumulating in brain. Here, we investigated the effect of the most nutritional prevalent phytosterols and cholesterol on APP processing. In general, phytosterols are less amyloidogenic than cholesterol. However, only one phytosterol, stigmasterol, reduced Aβ generation by (1) directly decreasing β-secretase activity, (2) reducing expression of all γ-secretase components, (3) reducing cholesterol and presenilin distribution in lipid rafts implicated in amyloidogenic APP cleavage, and by (4) decreasing BACE1 internalization to endosomal compartments, involved in APP β-secretase cleavage. Mice fed with stigmasterol-enriched diets confirmed protective effectsin vivo, suggesting that dietary intake of phytosterol blends mainly containing stigmasterol might be beneficial in preventing AD.
Parceling Human Accumbens into Putative Core and Shell Dissociates Encoding of Values for Reward and Pain
Authors: Baliki Marwan N. , Mansour Ali , Baria Alex T. , Huang Lejian , Berger Sara E. , Fields Howard L. , Apkarian A. Vania
Published: October 2013

In addition to their well-established role in signaling rewarding outcomes and reward-predictive cues and in mediating positive reinforcement, there is growing evidence that nucleus accumbens (NAc) neurons also signal aversive events and cues that predict them. Here we use diffusion tractography to subdivide the right NAc into lateral–rostral (putative core,pcore) and medial–caudal (putative shell,pshell) subdivisions in humans. The two subregions exhibited differential structural connectivity, based on probabilistic tractography, to prefrontal cortical and subcortical limbic regions. We also demonstrate unique roles for each of the two subdivisions for monetary reward and thermal pain perception tasks:pshell signaling impending pain and value predictions for monetary gambles andpcore activating with anticipation of cessation of thermal pain (signaling reward value of analgesia). We examined functional connectivity for resting state, monetary reward, and thermal pain tasks, and for all three conditions observed thatpcore andpshell of right NAc exhibit distinct patterns of synchrony (functional connectivity) to prefrontal cortical and subcortical limbic targets within the right hemisphere. To validate the NAc segregation, we mirrored the coordinates of right NAcpcore andpshell onto the left hemisphere and examined structural and resting state connectivity in the left hemisphere. This latter analysis closely replicated target-specific connections we obtained for the right hemisphere. Overall, we demonstrate that the human NAc can be parceled based on structural and functional connectivity, and that activity in these subdivisions differentially encodes values for expected pain relief and for expected monetary reward.
Learning-Related Translocation of δ-Opioid Receptors on Ventral Striatal Cholinergic Interneurons Mediates Choice between Goal-Directed Actions
Authors: Bertran-Gonzalez Jesus , Laurent Vincent , Chieng Billy C. , Christie MacDonald J. , Balleine Bernard W.
Published: October 2013

The ability of animals to extract predictive information from the environment to inform their future actions is a critical component of decision-making. This phenomenon is studied in the laboratory using the pavlovian–instrumental transfer protocol in which a stimulus predicting a specific pavlovian outcome biases choice toward those actions earning the predicted outcome. It is well established that this transfer effect is mediated by corticolimbic afferents on the nucleus accumbens shell (NAc-S), and recent evidence suggests that δ-opioid receptors (DORs) play an essential role in this effect. In DOR-eGFP knock-in mice, we show a persistent, learning-related plasticity in the translocation of DORs to the somatic plasma membrane of cholinergic interneurons (CINs) in the NAc-S during the encoding of the specific stimulus–outcome associations essential for pavlovian–instrumental transfer. We found that increased membrane DOR expression reflected both stimulus-based predictions of reward and the degree to which these stimuli biased choice during the pavlovian–instrumental transfer test. Furthermore, this plasticity altered the firing pattern of CINs increasing the variance of action potential activity, an effect that was exaggerated by DOR stimulation. The relationship between the induction of membrane DOR expression in CINs and both pavlovian conditioning and pavlovian–instrumental transfer provides a highly specific function for DOR-related modulation in the NAc-S, and it is consistent with an emerging role for striatal CIN activity in the processing of predictive information. Therefore, our results reveal evidence of a long-term, experience-dependent plasticity in opioid receptor expression on striatal modulatory interneurons critical for the cognitive control of action.
Activation of Extrasynaptic NMDARs at Individual Parallel Fiber–Molecular Layer Interneuron Synapses in Cerebellum
Authors: Nahir Ben , Jahr Craig E.
Published: October 2013

NMDA receptors (NMDARs) expressed by cerebellar molecular layer interneurons (MLIs) are not activated by single exocytotic events but can respond to glutamate spillover following coactivation of adjacent parallel fibers (PFs), indicating that NMDARs are perisynaptic. Several types of synaptic plasticity rely on these receptors but whether they are activated at isolated synapses is not known. Using a combination of electrophysiological and optical recording techniques in acute slices of rat cerebellum, along with modeling, we find that repetitive activation of single PF–MLI synapses can activate NMDARs in MLIs. High-frequency stimulation, multivesicular release (MVR), or asynchronous release can each activate NMDARs. Frequency facilitation was found at all PF–MLI synapses but, while some showed robust MVR with increased release probability, most were limited to univesicular release. Together, these results reveal a functional diversity of PF synapses, which use different mechanisms to activate NMDARs.
Ovarian Hormone Loss Impairs Excitatory Synaptic Transmission at Hippocampal CA3–CA1 Synapses
Authors: Wu Wendy W. , Bryant Damani N. , Dorsa Daniel M. , Adelman John P. , Maylie James
Published: October 2013

Premature and long-term ovarian hormone loss following ovariectomy (OVX) is associated with cognitive impairment. This condition is prevented by estradiol (E2) therapy when initiated shortly following OVX but not after substantial delay. To determine whether these clinical findings are correlated with changes in synaptic functions, we used adult OVX rats to evaluate the consequences of short-term (7–10 d, OVXControl) and long-term (∼5 months, OVXLT) ovarian hormone loss, as well as subsequentin vivoE2treatment, on excitatory synaptic transmission at the hippocampal CA3–CA1 synapses important for learning and memory. The results show that ovarian hormone loss was associated with a marked decrease in synaptic strength. E2treatment increased synaptic strength in OVXControlbut not OVXLTrats, demonstrating a change in the efficacy for E25 months following OVX. E2also had a more rapid effect: within minutes of bath application, E2acutely increased synaptic strength in all groups except OVXLTrats that did not receivein vivoE2treatment. E2's acute effect was mediated postsynaptically, and required Ca2+influx through the voltage-gated Ca2+channels. Despite E2's acute effect, synaptic strength of OVXLTrats remained significantly lower than that of OVXControlrats. Thus, changes in CA3–CA1 synaptic transmission associated with ovarian hormone loss cannot be fully reversed with delayed E2treatment. Given that synaptic strength at CA3–CA1 synapses is related to the ability to learn hippocampus-dependent tasks, these findings provide additional insights for understanding cognitive impairment-associated long-term ovarian hormone loss and ineffectiveness for delayed E2treatment to maintain cognitive functions.
On the Dissociation between Microsaccade Rate and Direction after Peripheral Cues: Microsaccadic Inhibition Revisited
Authors: Hafed Ziad M. , Ignashchenkova Alla
Published: October 2013

Microsaccades during fixation exhibit distinct time courses of frequency and direction modulations after stimulus onsets, but the mechanisms for these modulations are unresolved. On the one hand, microsaccade rate drops within <100 ms after stimulus onset, a phenomenon described as microsaccadic inhibition. On the other, the directions of the rare microsaccades that do occur during inhibition are, surprisingly, the most highly correlated with stimulus location. Here we show, using a combined computational and experimental approach, that these apparently dichotomous observations can simply result from a single mechanism: the phase resetting by stimulus onsets of ongoing microsaccadic oscillatory rhythms during fixation. Using experiments on monkeys and model simulations, we show that stimulus onsets act as countermanding stimuli, such as those in large saccadic countermanding tasks: they cancel an upcoming movement program and start a competing one, thus implementing phase resetting. We also show that the rare microsaccades occurring during microsaccadic inhibition are simply noncanceled movements in the countermanding framework and that they reflect the instantaneous state of visual representations expected in spatial maps representing stimuli. Remarkably, a dynamic interaction between the efficacy of the countermanding process and the metrics of the microsaccade being countermanded not only explains microsaccade rate changes, but it also predicts the time course patterns of microsaccade directions and amplitudes. Our parsimonious framework for understanding microsaccadic modulations around stimulus onsets allows analyzing microsaccades (and larger saccades) using the extensive toolkit of oscillatory dynamical systems often used for modeling spiking neurons, and it constrains neural models of microsaccade triggering.
Functional Maturation of the Executive System during Adolescence
Authors: Satterthwaite Theodore D. , Wolf Daniel H. , Erus Guray , Ruparel Kosha , Elliott Mark A. , Gennatas Efstathios D. , Hopson Ryan , Jackson Chad , Prabhakaran Karthik , Bilker Warren B. , Calkins Monica E. , Loughead James , Smith Alex , Roalf David R. , Hakonarson Hakon , Verma Ragini , Davatzikos Christos , Gur Ruben C. , Gur Raquel E.
Published: October 2013

Adolescence is characterized by rapid development of executive function. Working memory (WM) is a key element of executive function, but it is not known what brain changes during adolescence allow improved WM performance. Using a fractaln-back fMRI paradigm, we investigated brain responses to WM load in 951 human youths aged 8–22 years. Compared with more limited associations with age, WM performance was robustly associated with both executive network activation and deactivation of the default mode network. Multivariate patterns of brain activation predicted task performance with a high degree of accuracy, and also mediated the observed age-related improvements in WM performance. These results delineate a process of functional maturation of the executive system, and suggest that this process allows for the improvement of cognitive capability seen during adolescence.
Speed-Dependent Contribution of Callosal Pathways to Ipsilateral Movements
Authors: Tazoe Toshiki , Perez Monica A.
Published: October 2013

Transcallosal inhibitory interactions between primary motor cortices are important to suppress unintended movements in a resting limb during voluntary activation of the contralateral limb. The functional contribution of transcallosal inhibition targeting the voluntary active limb remains unknown. Using transcranial magnetic stimulation, we examined transcallosal inhibition [by measuring interhemispheric inhibition (IHI) and the ipsilateral silent period (iSP)] in the preparatory and execution phases of isotonic slower self-paced and ballistic movements performed by the ipsilateral index finger into abduction and the elbow into flexion in intact humans. We demonstrate decreased IHI in the preparatory phase of self-paced and ballistic index finger and elbow movements compared to rest; the decrease in IHI was larger during ballistic than self-paced movements. In contrast, in the execution phase, IHI and the iSP increased during ballistic compared to self-paced movements. Transcallosal inhibition was negatively correlated with reaction times in the preparatory phase and positively correlated with movement amplitude in the execution phase. Together, our results demonstrate a widespread contribution of transcallosal inhibition to ipsilateral movements of different speeds with a functional role during rapid movements; at faster speeds, decreased transcallosal inhibition in the preparatory phase may contribute to start movements rapidly, while the increase in the execution phase may contribute to stop the movement. We argue that transcallosal pathways enable signaling of the time of discrete behavioral events during ipsilateral movements, which is amplified by the speed of a movement.
A Critical Role for Macrophages Near Axotomized Neuronal Cell Bodies in Stimulating Nerve Regeneration
Authors: Niemi Jon P. , DeFrancesco-Lisowitz Alicia , Roldán-Hernández Lilinete , Lindborg Jane A. , Mandell Daniel , Zigmond Richard E.
Published: October 2013

Macrophages have been implicated in peripheral nerve regeneration for some time, supposedly through their involvement in Wallerian degeneration, the process by which the distal nerve degenerates after axotomy and is cleared by phagocytosis. Thus, in several studies in which macrophage accumulation in the distal nerve was reduced and Wallerian degeneration inhibited, regeneration was delayed. However, this interpretation ignores the more recent findings that macrophages also accumulate around axotomized cell bodies. The function of macrophage action at this second site has not been clear. In two mutant strains of mice, the slow Wallerian degeneration (Wlds) mouse and the chemokine receptor CCR2 knock-out mouse, we report that macrophage accumulation after axotomy was abolished in both the dorsal root ganglion (DRG) and the distal sciatic nerve. To measure neurite outgrowth, DRG neurons were given a conditioning lesion, and outgrowth was measuredin vitro7 d later in the absence of the distal nerve segment. The increased growth normally seen after a conditioning lesion did not occur or was reduced inWldsorCCR2−/−mice. In the superior cervical ganglion (SCG), particularly inWldsmice, macrophage accumulation was reduced but not abolished after axotomy. In SCG neurons fromWldsmice, the conditioning lesion response was unchanged; however, inCCR2−/−mice in which the effect on macrophage accumulation was greater, SCG neurite outgrowth was significantly reduced. These results indicate that macrophages affect neurite outgrowth by acting at the level of peripheral ganglia in addition to any effects they might produce by facilitation of Wallerian degeneration.
Neural Evidence for Individual and Cultural Variability in the Social Comparison Effect
Authors: Kang Pyungwon , Lee Yongsil , Choi Incheol , Kim Hackjin
Published: October 2013

Although several studies have investigated the neural mechanism of social comparison, it remains unclear whether and how cultural membership, particularly independent versus interdependent cultures, may differentially shape the neural processes underlying social comparison. In the present functional magnetic resonance imaging (fMRI) study, we examined the behaviors and neural response patterns of Korean (i.e., interdependent culture) and American (i.e., independent culture) participants while performing a financial gambling task simultaneously and independently with a partner. Upon seeing the partner's income, greater modulation of the activity in the ventral striatum (VS) and the ventromedial prefrontal cortex (vmPFC) by relative gain was observed in Korean than American participants, suggesting greater sensitivity of Koreans toward social comparison. The strength of functional connectivity between the VS and the vmPFC predicted individual variability in the degree to which participants' decisions were affected by relative incomes. Additional model-based fMRI analysis further confirmed the primary role of the vmPFC in biasing decisions based on relative incomes. In summary, the present study provides the first neural evidence for decision biases due to social comparison and their individual and cultural variations.
Becoming a Black Researcher
Authors: Roberts Lorna
Published: October 2013

Critical race theory (CRT) emerged from the U.S. context, and many question the validity of its application to spaces beyond the United States; however, for many black academics in the UK, it has a powerful resonance. Where many in the academy have dismissed the viability of the concept of race in favour of the term ethnicity – or they privilege class – in any discussion of inequalities, CRT recognises the salience of race, centralising it and analysing the ways in which race and racism continue to shape life experiences. CRT has provided an intellectual space for a growing community of academics in England to explore not only our own racial positioning within the academy and wider society but also that of the communities we work with in our research to achieve greater social justice. This paper explores the significance of CRT to the author's biography and intellectual journey.
Opening it All Up
Authors: Lancaster Lesley
Published: October 2013

This paper examines the contention that an ‘autonomous’ model of literacy dominates pedagogy and research, emphasising technical outcomes for even the youngest children. It considers theoretical obstacles to alternative research paradigms, particularly a stance that views writing as ‘talk written down’. Studies of early mark-making suggest that children's signs are always intentional, already displaying some evidence of systemic principles in relation to writing, drawing, and number. This is supported by theoretical stances in multimodality, social semiotics, and phenomenology. These positions substantiate the development of new methodologies in early literacy research, emphasising interactive processes rather than outcomes. The paper considers the use of micro, multimodal transcripts of video evidence to examine the process of children's sign-making. It looks at vignettes of transcribed data involving children under the age of 3, and the use of microanalysis to investigate early writing.
Understanding nuclear receptor form and function using structural biology
Authors: Rastinejad Fraydoon , Huang Pengxiang , Chandra Vikas , Khorasanizadeh Sepideh
Published: October 2013

Nuclear receptors (NRs) are a major transcription factor family whose members selectively bind small-molecule lipophilic ligands and transduce those signals into specific changes in gene programs. For over two decades, structural biology efforts were focused exclusively on the individual ligand-binding domains (LBDs) or DNA-binding domains of NRs. These analyses revealed the basis for both ligand and DNA binding and also revealed receptor conformations representing both the activated and repressed states. Additionally, crystallographic studies explained how NR LBD surfaces recognize discrete portions of transcriptional coregulators. The many structural snapshots of LBDs have also guided the development of synthetic ligands with therapeutic potential. Yet, the exclusive structural focus on isolated NR domains has made it difficult to conceptualize how all the NR polypeptide segments are coordinated physically and functionally in the context of receptor quaternary architectures. Newly emerged crystal structures of the peroxisome proliferator-activated receptor-γ–retinoid X receptor α (PPARγ–RXRα) heterodimer and hepatocyte nuclear factor (HNF)-4α homodimer have recently revealed the higher order organizations of these receptor complexes on DNA, as well as the complexity and uniqueness of their domain–domain interfaces. These emerging structural advances promise to better explain how signals in one domain can be allosterically transmitted to distal receptor domains, also providing much better frameworks for guiding future drug discovery efforts.
Linearization of the products of the generalized Lauricella polynomials and the multivariate Laguerre polynomials via their integral representations
Authors: Liu Shuoh-Jung , Lin Shy-Der , Lu Han-Chun , Srivastava H.
Published: October 2013

In this paper, the authors investigate the linearization problems associated with two families of generalized Lauricella polynomials of the first and second kinds. By means of their multiple integral representations, it is shown how one can linearize the product of two different members of each of these two families of the generalized Lauricella polynomials. Upon suitable specialization of the main results presented in this paper, the corresponding integral representations are deduced for such familiar classes of multivariable hypergeometric polynomials as (for example) the Lauricella polynomials FA(r) in r variables, the Appell polynomials F2 in two variables and the multivariable Laguerre polynomials. Each of these integral representations, which are derived as special cases of the main results in this paper, may also be viewed as a linearization relationship for the product of two different members of the associated family of multivariable hypergeometric polynomials.
Incorporating Biodopants into PEDOT Conducting Polymers: Impact of Biodopant on polymer properties and biocompatibility
Authors: Molino Paul J. , Tibbens Anthony , Kapsa Robert M.I. , Wallace Gordon G.
Published: October 2013

Poly(3,4-ethylenedioxythiophene) (PEDOT) was polymerized with the biological dopants dextran sulphate and chondroitin sulphate. Polymer physical and mechanical properties were investigated using quartz crystal microgravimetry with dissipation monitoring and atomic force microscopy, revealing polymer shear modulus and interfacial roughness to be significantly altered as a function of the dopant species. The adsorption of fibronectin, an important extracellular protein that is critical for a range of cellular functions and processes, was investigated using QCM-D, revealing protein adsorption to be increased on the DS doped PEDOT film relative to the CS doped film. PEDOT films have traditionally been doped with synthetic counterions such as polystyrene sulphonate (PSS), however the incorporation of biological molecules as the counterion, which has been shown to improve polymer biofunctionality, has received far less attention. In particular, there has been little detailed study on the impact of incorporating polyelectrolyte biomolecules into the PEDOT polymer matrix on fundamental polymer properties which are critical for biomedical applications. This investigation provides a detailed characterization of the interfacial and mechanical properties of biologically doped PEDOT films, as well as the efficacy of the composite films to bind and retain extracellular proteins of the type that are critical to the biocompatibility of the polymeric material.
Atomic simulations of GB sliding in pure and segregated bicrystals
Authors: Yuasa Motohiro , Chino Yasumasa , Mabuchi Mamoru
Published: October 2013

Grain boundary (GB) sliding is an important deformation mode in polycrystals, and it has been extensively investigated, for example, there are many studies on influences of the atomic geometry in the GB region. However, it is important to investigate GB sliding from the electronic structure of GB for deeper understandings of the sliding mechanisms. In the present work, we investigated the GBs sliding in pure and segregated bicrystals with classical molecular dynamics (MD) simulations and first-principles calculations. It is accepted that the sliding rate is affected by the GB energy. However, there was no correlation between the sliding rate and the GB energy in either the pure or the segregated bicrystals. First-principles calculations revealed that the sliding rate calculated by the MD simulations increases with decreasing minimum charge density at the bond critical point in the GB. This held in both the pure and segregated bicrystals. It seems that the sliding rate depends on atomic movement at the minimum charge density sites.
Direct Observation of Atomic Arrangement around 90° Domain Wall in Lead Titanate Thin Films.
Authors: Kiguchi Takanori , Konno Toyohiko J. , Ehara Yoshitaka , Yamada Tomoaki , Funakubo Hiroshi
Published: October 2013

The growth mechanism of large-size domains in PbTiO3/SrTiO3 heteroepitaxial thin films was examined using annular bright field (ABF) – scanning transmission electron microscopy and geometric phase analysis (GPA). {101} domain walls surrounded 90° domains. The large 90° domain grows by the coalescence of the nano-size domains of less than 5 nm width. A strain map obtained from the GPA of ABF-STEM image showed that 90° domains interacted elastically and attractively with edge dislocations at PbTiO3/SrTiO3 interface through simple shear strain.
Tubarões e peixinhos: histórias de jovens protagonistas
Authors: Tommasi Livia De
Published: October 2013

O artigo apresenta as trajetórias de três jovens moradores de uma pequena cidade do interior do Nordeste, analisando seu trânsito para os projetos sociais da região, os conflitos que vivenciaram na relação com as organizações e com os gestores dos programas, bem como seu engajamento político e social. Os depoimentos dos jovens têm sido coletados por meio de entrevistas semiestruturadas, no âmbito de uma pesquisa sobre trajetórias de jovens envolvidos em programas sociais. A partir de suas trajetórias de vida, antes, durante e depois de seu ingresso nos programas, procuramos compreender os sentidos e as consequências desse envolvimento para além do que geralmente é apontado pela literatura com respeito à abertura de oportunidades de inserção social. Em particular, interrogamos sobre a natureza dos conflitos vivenciados e suas implicações políticas. A história deles é exemplar da forma como projetos sociais voltados ao público jovem atuam, tanto pela relação que se estabelece entre os jovens público-alvo e os promotores das iniciativas, quanto pela forma como os projetos se desenvolvem e seus princípios e objetivos (o protagonismo, o empoderamento, a responsabilidade social) são concretizados. Do ponto de vista da mobilidade social, as trajetórias desses jovens podem ser consideradas bem-sucedidas; no entanto, seus sonhos de autonomia e organização coletiva ficaram frustrados. O lugar social que eles ocupam é, ainda, um lugar subalterno. Suas histórias são paradigmáticas de como, no âmbito da racionalidade neoliberal, a subjetividade se torna objeto, alvo e recurso de estratégias de regulação e as condutas são geridas não contra, mas sim através da liberdade individual.
Assessing the effects of the São Paulo's metropolitan beltway on residential land prices
Authors: Maciel Vladimir Fernandes , Biderman Ciro
Published: October 2013

This paper estimates the effect of highways on land prices using the implementation of the west branch of a large beltway around Sao Paulo Metropolitan Area. This is a unique opportunity since the beltway is being implemented by branches. So, it is possible to use the zones surrounding the branches where construction has actually started as a treatment group to be compared with zones surrounding branches for which construction has not started yet. Since we have a proxy for land price data before and after construction, it is possible to estimate the impact by difference-in-difference. The evidence is that there are significant and asymmetrical effects caused by the highway construction. Parcels located close to ramps outbound of the track observed an increase in price faster than similar zones close to other (planned) branches. For parcels located inbound of the beltway, relatively far from the track (between 2.5 km and 5 km), the effects of construction and delivery/operation faced a (relative) decline in land prices. These results have consequences for transportation finance; betterment levies and value capture taxes; and welfare.
A Double-Blind, Randomized Phase II Study to Evaluate the Safety and Efficacy of Acetyl-L-Carnitine in the Prevention of Sagopilone-Induced Peripheral Neuropathy
Authors: Campone Mario , Berton-Rigaud Dominique , Joly-Lobbedez Florence , Baurain Jean-Francois , Rolland Frédéric , Stenzl Arnulf , Fabbro Michel , Dijk Marjan , Pinkert Jörg , Schmelter Thomas , Bont Natasja , Pautier Patricia
Published: October 2013

Background.

Peripheral neuropathy (PN) is a recognized side effect of microtubule-targeting agents and the most clinically relevant toxicity observed with the epothilone sagopilone (SAG). Studies suggest that acetyl-L-carnitine (ALC) may prevent chemotherapy-induced PN. We conducted a prospective, placebo (PBO)-controlled, double-blind, randomized trial to investigate the safety and efficacy of ALC for the prevention of SAG-induced PN.

Methods.

Patients with ovarian cancer (OC) or castration-resistant prostate cancer (CRPC) and no evidence of neuropathy received SAG (16 mg/m2 intravenously over 3 hours every 3 weeks) with ALC (1,000 mg every 3 days) or placebo (PBO). The primary endpoint was incidence of PN within six or fewer cycles in both treatment groups.

Results.

Overall, 150 patients enrolled (98 OC patients, 52 CRPC patients), with 75 per treatment arm. No significant difference in overall PN incidence was observed between treatment arms. The incidence of grade ≥3 PN was significantly lower in the ALC arm in OC patients. Median duration of neuropathy was similar between treatment arms. The best overall response (according to the modified Response Evaluation Criteria in Solid Tumors), response according to tumor markers, time-to-event variables, and discontinuations because of adverse events (AEs) were comparable between treatment arms.

Conclusion.

Administration of ALC with SAG did not result in a significant difference in overall PN incidence compared with a PBO. OC patients in the SAG/ALC arm had a significantly lower incidence of grade 3 or 4 PN compared with OC patients in the SAG/PBO arm.
Influence of grain size and mineralogy on the porosity/cement ratio
Authors: Rios S. , Viana da Fonseca A. , Consoli N. C. , Floss M. , Cristelo N.
Published: October 2013

The porosity/cement ratio is defined as the ratio between porosity and the volumetric cement content (volume of cement over the total volume) and it is often adjusted by an exponent (ξ) to the volumetric cement content ([Formula: see text]), which seems to depend on the type of soil. This ratio is very useful to analyse artificially cemented soils and it depends on easily calculated moulding properties. Although there are already some results regarding the correlation of this ratio with the mechanical behaviour of different soils, a theory explaining the variation of the exponent ξ has yet to be established. In this work, the influence of grain size and mineralogy on ξ was pursued, considering them to be the most important factors. For that purpose, a soil was divided into three different fractions, whose grain size distribution and mineralogy were known, and the exponents obtained correlating the ratio with the maximum shear modulus or the unconfined compression strength were compared. The results show that the grain size distribution explains part of the ξ variation, but mineralogy and particle shape seem to have the most decisive influence. This was even more evident when comparing two uniform sands.
‘Mapping the Underworld’: recent developments in vibro-acoustic techniques to locate buried infrastructure
Authors: Muggleton J. M. , Rustighi E.
Published: October 2013

A major UK initiative entitled Mapping the Underworld (MTU) is seeking to address the serious social, environmental and economic consequences arising from an inability to locate – accurately and comprehensively – buried utility service infrastructure without resorting to extensive excavations. MTU aims to develop and prove the efficacy of a multi-sensor device for accurate remote buried utility service detection, location and, where possible, identification. One of the technologies to be incorporated in the device is low-frequency vibro-acoustics, and a number of different vibro-acoustic methods for detecting buried infrastructure have been investigated. The latest developments in the vibro-acoustic location research are presented here. Three complementary methods are described, one of which involves direct excitation of the buried asset and the other two require no such direct access. All involve measurement of the ground surface vibration as a result of the excitation, whether of the ground or of the buried asset directly. Together, these techniques constitute a substantial step change in the way buried infrastructure can be detected using vibro-acoustic methods.
Healing of biologically induced cemented sands
Authors: Montoya B. M. , Dejong J. T.
Published: October 2013

Microbial-induced calcite precipitation (MICP) is a novel bio-mediated ground improvement method that can be used to increase the shear strength and stiffness of sand. One of the benefits of the MICP treatment process is the ability to heal degraded calcite bonds post-shearing. The healed bonds can then improve the sand properties (small strain stiffness and peak strength) compared with those of the pre-shearing condition. The MICP healing process was evaluated using monotonic undrained shearing and dynamic centrifuge tests, and comparing the sand behaviour before and after the healing process. Similar or improved behaviour was observed after the healing process. This healing ability implies that degraded MICP-treated sands can be healed after loading (e.g. in an earthquake) to their original level of treatment to prevent additional settlements or damage from subsequent loading (e.g. aftershocks).
UK military use of concrete in the nineteenth and twentieth centuries
Authors: Simpson Deryk E.
Published: October 2013

The use of concrete for military purposes in the UK is probably not well appreciated and possibly overlooked by many engineers. This paper considers how concrete was used to provide defensive measures against the perceived threats to UK security in the nineteenth and twentieth centuries.
Deconstructing the surrogate species concept: a life history approach to the protection of ecosystem services
Authors: Banks John E. , Stark John D. , Vargas Roger I. , Ackleh Azmy S.
Published: October 2013

The use of the surrogate species concept is widespread in environmental risk assessment and in efforts to protect species that provide ecosystem services, yet there are no standard protocols for the choice of surrogates. Surrogates are often chosen on the basis of convenience or vague resemblances in physiology or life history to species of concern. Furthermore, our ability to predict how species of concern will fare when subjected to disturbances such as environmental contaminants or toxicants is often based on woefully misleading comparisons of static toxicity tests. Here we present an alternative approach that features a simple mathematical model parameterized with life history data applied to an assemblage of species that provide an important ecosystem service: a suite of parasitoid wasps that provide biological control of agricultural pests. Our results indicate that these parasitoid wasp species have different population responses to toxic insult—that is, we cannot predict how all four species will react to pesticide exposure simply by extrapolating from the response of any one species. Furthermore, sensitivity analysis of survivorship and reproduction demonstrates that the life stage most sensitive to pesticide disturbance varies among species. Taken together, our results suggest that the ability to predict the fate of a suite of species using the response of just one species (the surrogate species concept) is widely variable and potentially misleading.
Management Credibility and Investment Risk: An Experimental Investigation of Lease Accounting Alternatives
Authors: Krische Susan D. , Sanders Paula R. , Smith Steven D.
Published: October 2013

This paper examines how users' understanding of the financial statement impact of accounting alternatives and the disclosure choices management has made jointly influence users' assessments of management credibility and investment risk. Specifically, in a lease obligation setting, management's reporting choice (i.e., recognition versus disclosure), the presence of a supplemental reconciliation from disclosure to recognition, and the source of that reconciliation (as company management or an independent analyst) are manipulated. As predicted, the findings indicate that users assess a management credibility deficiency only when they understand both the financial statement implications of an incentive-consistent reporting choice and that management has not been forthcoming about that choice. In contrast, users' understanding of the financial statement implications of the reporting choice is sufficient to influence their investment risk judgments. This research extends the literature on managerial reporting by documenting necessary knowledge conditions for users to make differential assessments of managers.
Severe Hypoglycemia and Cognitive Decline in Older People With Type 2 Diabetes: The Edinburgh Type 2 Diabetes Study
Authors: Feinkohl Insa , Aung Phyu Phyu , Keller Marketa , Robertson Christine M. , Morling Joanne R. , McLachlan Stela , Deary Ian J. , Frier Brian M. , Strachan Mark W.J. , Price Jackie F. ,   on behalf of the Edinburgh Type 2 Diabetes Study (ET2DS) Investigators
Published: October 2013

OBJECTIVE

People with type 2 diabetes are at increased risk of age-related cognitive decline and dementia. Hypoglycemia is a candidate risk factor, but the direction of association between episodes of severe hypoglycemia and cognitive decline in type 2 diabetes remains uncertain.

RESEARCH DESIGN AND METHODS

In the Edinburgh Type 2 Diabetes Study, cognitive function was assessed in 831 adults with type 2 diabetes (aged 60–75 years) at baseline and after 4 years. Scores on seven neuropsychological tests were combined into a standardized general ability factor g. Self-reported history of severe hypoglycemia at baseline (history of hypoglycemia) and at follow-up (incident hypoglycemia) was recorded.

RESULTS

A history of hypoglycemia was reported by 9.3% of subjects, and 10.2% reported incident hypoglycemia. Incident hypoglycemia was associated with poorer cognitive ability at baseline (age- and sex-adjusted odds ratio for lowest tertile of g 2.04 [95% CI 1.25–3.31], P = 0.004). Both history of hypoglycemia and incident hypoglycemia were also associated with greater cognitive decline during follow-up (mean follow-up g adjusted for age, sex, and baseline g −0.25 vs. 0.03 [P = 0.02] and −0.28 vs. 0.04 [P = 0.01], respectively), including after addition of vascular risk factors and cardiovascular and microvascular disease to the models (−0.23 vs. 0.03 [P = 0.04] and −0.21 vs. 0.05 [P = 0.03], respectively).

CONCLUSIONS

The relationship between cognitive impairment and hypoglycemia appeared complex, with severe hypoglycemia associated with both poorer initial cognitive ability and accelerated cognitive decline.