bluuebunny/crossref_metadata_2025 huggingface dataset:
Modulation of β-amyloid by a single dose of GSK933776 in patients with mild Alzheimer’s disease: a phase I study
Authors: Leyhe Thomas , Andreasen Niels , Simeoni Monica , Reich Arno , von Arnim Christine AF , Tong Xin , Yeo Astrid , Khan Shahid , Loercher Amy , Chalker Michelle , Hottenstein Charles , Zetterberg Henrik , Hilpert Jan , Mistry Prafull
Published: April 2014

Introduction

In this study, we evaluated the safety and pharmacodynamic effects of the Fc-inactivated anti-β-amyloid (anti-Aβ) monoclonal antibody GSK933776 in patients with mild Alzheimer’s disease and mild cognitive impairment. Aβ and tau levels were investigated in cerebrospinal fluid (CSF), and the relationship between Aβ levels and Aβ modulation in plasma was explored. The feasibility of a continuous sampling method using a lumbar catheter was assessed.

Methods

This trial was a phase I, open-label, uncontrolled, single-dose, exploratory experimental medicine study of intravenous GSK933776 at doses of 1 mg/kg, 3 mg/kg or 6 mg/kg (n = 6/group). The time course of plasma and CSF concentrations of GSK933776 and Aβ was assessed. Sample size was based on feasibility, and no formal statistical analyses were performed.

Results

Following administration of GSK933776 at doses of 1 mg/kg, 3 mg/kg and 6 mg/kg, there were decreases from baseline in CSF Aβ1–42 (from 0 to 12 hours) by 22.8 pg/ml (6.2%), 43.5 pg/ml (9.2%) and 60.5 pg/ml (12.5%), respectively. Plasma concentrations of total Aβ18–35 and Aβ4228–42 increased immediately after infusion and CSF tau concentration increased slightly, but did not significantly change, following administration of all doses of GSK933776. Pharmacokinetics confirmed the presence of GSK933776 in the CSF, which exhibited a dose–response relationship. One patient underwent minor surgery without sequelae following a ruptured lumbar catheter.

Conclusion

GSK933776 demonstrated pharmacological activity and target engagement in CSF and plasma, and the continuous sampling method via a catheter successfully assessed the Aβ changes following single-dose administration of GSK933776.

Trial registration

ClinicalTrials.gov Identifier: NCT01424436. Registered 4 August 2011
Prediction of mortality in adult patients with severe acute lung failure receiving veno-venous extracorporeal membrane oxygenation: a prospective observational study
Authors: Enger Tone Bull , Philipp Alois , Videm Vibeke , Lubnow Matthias , Wahba Alexander , Fischer Marcus , Schmid Christof , Bein Thomas , Müller Thomas
Published: April 2014

Introduction

Veno-venous extracorporeal membrane oxygenation (vvECMO) can be a life-saving therapy in patients with severe acute lung failure refractory to conventional therapy. Nevertheless, vvECMO is a procedure associated with high costs and resource utilization. The aim of this study was to assess published models for prediction of mortality following vvECMO and optimize an alternative model.

Methods

Established mortality risk scores were validated to assess their usefulness in 304 adult patients undergoing vvECMO for refractory lung failure at the University Medical Center Regensburg from 2008 to 2013. A parsimonious prediction model was developed based on variables available before ECMO initiation using logistic regression modelling. We then assessed whether addition of variables available one day after ECMO implementation enhanced mortality prediction. Models were internally validated and calibrated by bootstrapping (400 runs). Predictive ability, goodness-of-fit and model discrimination were compared across the different models.

Results

In the present study population, existing mortality prediction tools for vvECMO patients showed suboptimal performance. Evaluated before vvECMO initiation, a logistic prediction model comprising age, immunocompromised state, artificial minute ventilation, pre-ECMO serum lactate and hemoglobin concentrations showed best mortality prediction in our patients (area under curve, AUC: 0.75). Additional information about norepinephrine dosage, fraction of inspired oxygen, C-reactive protein and fibrinogen concentrations the first day following ECMO initiation further improved discrimination (AUC: 0.79, P = 0.03) and predictive ability (likelihood ratio test, P < 0.001). When classifying patients as lower (<40%) or higher (>80%) risk based on their predicted mortality, the pre-ECMO and day1-on-ECMO models had negative/positive predictive values of 76%/82% and 82%/81%, respectively.

Conclusions

While pre-ECMO mortality prediction remains a challenge due to large patient heterogeneity, evaluation one day after ECMO initiation may improve the ability to separate lower- and higher-risk patients. Our findings support the clinical perception that chronic health condition, high comorbidity and reduced functional reserves are strongly related to survival during and following ECMO support. Renewed evaluation the first day after ECMO initiation may provide enhanced guidance for further handling of ECMO patients. Despite the usefulness of prediction models, thorough clinical evaluation should always represent the cornerstone in decision for ECMO.
Temporal Evolution of Catechol-Based Belousov–Zhabotinsky Chemical Oscillating System in Presence of Antioxidants
Authors: Shah Ishfaq Ahmad , Peerzada Ghulam Mustafa , Ganaie Nadeem Bashir , Gull Usma
Published: April 2014

The perturbation effect of various antioxidants viz. ascorbic acid, glutathione, inosine, and N-acetylcysteine is monitored at 30 °C under stirred batch conditions and has a good sensitivity for the determination of these antioxidants. The addition of these antioxidants to the BZ mixture influences the oscillatory parameters to an extent that depends on the concentration of the antioxidant and higher concentrations as such were found to quench the oscillations. The experimental results have shown that the number of oscillations decreases on increasing the concentration of antioxidant. The detection limit is found to be less than 1.0 × 10−7 mol L−1. In the case of glutathione, ascorbic acid, and N-acetylcysteine, a linear relationship (R2 = 0.99) between time period and the [antioxidant] has been obtained over a concentration range of 0.025–0.6, 0.0125–1.0, and 0.00625–0.8 mol L−1 with detection limits 6.925 × 10−5, 3.462 × 10−5, and 1.371 × 10−5 mol L−1 respectively whereas that for inosine a linear relationship (R2 = 0.98) between amplitude and [antioxidant] has been obtained over a concentration range of 0.05–0.7 mol L−1 and the detection limit is 1.385 × 10−4 mol L−1. Further, interactions of these antioxidants with BZ reagents were confirmed by cyclic voltammetry, which paved the way for explaining the mechanisms involved.
Simultaneous Measurement of Surface Tension and Its Gradient around Moving Camphor Boat on Water Surface
Authors: Karasawa Yuichiro , Oshima Shogo , Nomoto Tomonori , Toyota Taro , Fujinami Masanori
Published: April 2014

The distribution of surface tension on the front and rear sides of a camphor boat continuously moving on an aqueous-phase camphor solution was observed by the time-resolved quasi-elastic laser scattering method. The uniform motion of the boat was induced by a difference in the surface tension between the front and rear sides. A surface-tension gradient developed along the rear side, resulting in Marangoni convection that decelerated the boat.
Post-transcriptional regulation of meiotic genes by a nuclear RNA silencing complex
Authors: Egan Emily D. , Braun Craig R. , Gygi Steven P. , Moazed Danesh
Published: April 2014

RNA is a central component of gene-silencing pathways that regulate diverse cellular processes. In the fission yeast Schizosaccharomyces pombe, an RNA-based mechanism represses meiotic gene expression during vegetative growth. This pathway depends on the zinc finger protein Red1, which is required to degrade meiotic mRNAs as well as to target histone H3 lysine 9 (H3K9) methylation, a repressive chromatin mark, to a subset of meiotic genes. However, the mechanism of Red1 function is unknown. Here we use affinity purification and mass spectrometry to identify a Red1-containing nuclear RNA silencing (NURS) complex. In addition to Red1, this complex includes the Mtl1, Red5, Ars2, Rmn1, and Iss10 proteins and associates with several other complexes that are involved in either signaling or mediating RNA silencing. By analyzing the effects of gene knockouts and inducible knockdown alleles, we show that NURS subunits regulate RNA degradation and H3K9 methylation at meiotic genes. We also identify roles for individual NURS subunits in interactions with Mmi1, an RNA-binding protein that marks meiotic RNAs for destruction, and the nuclear exosome RNA degradation complex. Finally, we show that the levels of H3K9 methylation at meiotic genes are not sufficient to restrict RNA polymerase II access or repress gene expression during vegetative growth. Our results demonstrate that Red1 partners with other proteins to silence meiotic gene expression at the post-transcriptional level. Conservation of a NURS-like complex in human cells suggests that this pathway plays an ancient and fundamental role in RNA silencing.
Urbanization Dynamics in Egypt: Factors, Trends, Perspectives
Authors: Julia Zinkina  , Andrey Korotayev
Published: April 2014

The article analyzes the specifics of urbanization dynamics in Egypt, which is noteworthy for a number of reasons. First, there was a shift from the logistic trend in the 1970s, and the share of urban population stopped growing. The UN data analysis shows that such a shift usually occurs against the background of very serious economic difficulties (and other problems associated with them). However, the urban population proportion stopped growing in Egypt when the country was experiencing a period of exceedingly rapid economic growth. We find labor migration of unprecedented scale to be the main reason which engendered this seemingly paradoxical situation. We further proceed to analyze the UN forecast on the dynamics of the Egyptian urban population proportion up to 2050, which implies a return to the logistic trend and rapid growth of the urban population share, which is fraught with socio-political instability risks. However, we present data proving that the logistic urbanization trajectory is not inevitable for Egypt, and the destabilization risks connected with the rapid increase of urban population share are largely irrelevant to Egypt in the forecasted period.
Regime Change and Arab Countries' Lobbying in the United States
Authors: Sergey Kostyaev
Published: April 2014

In this article lobbying by several Arab countries in the United States is analyzed to answer two
questions: What are the ramifications of a regime change for lobbying strategy in the United States?
Does lobbying matter in securing US government support? First, the study demonstrates that regime
change in Tunisia, Egypt and Libya has had no effect on their lobbying in the United States so far.
The analysis of lobbying by countries which eschewed regime change—Bahrain, Saudi Arabia, and
Pakistan—surprisingly comes to the same conclusion. Second, the ability of troubled regimes to
peacefully control their own populace is more important for securing US support than lobbying.
Bahrain's Arrested Revolution
Authors: Stephen Zunes
Published: April 2014

This article provides an overview and analysis of the 2011 pro-democracy struggle in Bahrain, focusing in particular on the role of strategic nonviolent action and the foreign policy of the United States. It argues that Bahrain's progressive and pluralistic tradition would have made the possibilities of a democratic transition more promising than in many Arab states, but the ruthlessness and uncompromising posture of the government, combined with Saudi-led intervention and a refusal by the United States to support democratic forces, led to the movement's suppression. The article also challenges exaggerated accounts of the sectarian dimension of the conflict and faults the United States for its ongoing support for the Bahraini regime as a major contributor to the failure of the pro-democracy struggle.
The Roots and Causes of the 2011 Arab Uprisings
Authors: Kamal Eldin Osman Salih
Published: April 2014

This research article attempts to scrutinize the nature and causes of the Arab uprisings which took people by surprise globally throughout 2011 and into 2012. The article argues that the repressive, violent nature of the Arab regimes and their suppression of individual liberties against a backdrop of ongoing corruption and deterioration of the economy have been among the major factors leading to the Arab revolts. In addition, the article attempts to answer the query: why were the two repressive regimes of Tunisia and Egypt so quick to come undone, whereas dismantling the Libyan regime took much longer? Finally, the article tries to develop a causation analysis as to why the Arab regimes of Kuwait, Saudi Arabia, the United Arab Emirates, Qatar, the Sultanate of Oman, and Sudan have not faced major political protest.
Egypt: Revolutionary Process and Global Capitalist Crisis
Authors: Ibrahim G. Aoudé
Published: April 2014

The upheaval that has swept the Arab world, beginning in December 2010, reached Egypt on January 25, 2011. The article argues that capitalist globalization and ultimately the 2008 global financial crisis were main causes of the uprising. The Mubarak regime's privatization schemes exacerbated poverty and widened the already huge gap between rich and poor. Mubarak employed repression to ensure that no effective political opposition would materialize to challenge his authoritarian rule and crony capitalism. Strikes and demonstrations beginning in 2006 and the lead up to the uprising demonstrated that the fight for democracy and economic justice had been intertwined. The ouster of Mubarak has not improved the economic situation for the majority of the population and authoritarian rule remained under the military and since the election of the Islamist President Morsi. Popular resistance continues against the Islamists in power to bring about a secular regime that would establish democracy and economic justice.
The United States and the Arab Spring: The Dynamics of Political Engineering
Authors: Gamal M. Selim
Published: April 2014

This article purports to examine the role of the United States in the outbreak of the Arab Spring and the course of its subsequent paths. The main argument of this article is that the Arab Spring represented a major strategic surprise to the United States. It did not plan or facilitate the Arab Spring as the Tunisian, Egyptian, Yemeni and Bahraini regimes were performing to the best satisfaction of American interests in the Arab world. As the Arab Spring carried with it threats to American regional interests, the United States moved to secure its interests by steering Arab uprisings towards courses of action which best suit these interests.
The value frameworks and motivations for intergenerational transfers from older Australians
Authors: O’Dwyer Lisel Alice , Buckley Jennifer
Published: April 2014

Transfers of time and money from people aged 50 or more may be made upward to living parents or downward to children, or both. The role of family in such transfers has strong implications for the level of social support offered by the state. This article takes a qualitative approach to reveal the value frameworks and motivations behind these transfers, based on a subsample of 30 respondents from a larger Computer Assisted Telephone Interview (CATI) survey. Family solidarity is still a strong norm in Australian society but adherence to this norm is flexible. Most Australians expect the state to supplement interfamilial assistance.
Genotyping Accuracy of High-Resolution DNA Melting Instruments
Authors: Li Mei , Zhou Luming , Palais Robert A , Wittwer Carl T
Published: April 2014

BACKGROUND

High-resolution DNA melting is a closed-tube method for genotyping and variant scanning that depends on the thermal stability of PCR-generated products. Instruments vary in thermal precision, sample format, melting rates, acquisition, and software. Instrument genotyping accuracy has not been assessed.

METHODS

Each genotype of the single nucleotide variant (SNV) (c.3405–29A>T) of CPS1 (carbamoyl-phosphate synthase 1, mitochondrial) was amplified by PCR in the presence of LCGreen Plus with 4 PCR product lengths. After blinding and genotype randomization, samples were melted in 10 instrument configurations under conditions recommended by the manufacturer. For each configuration and PCR product length, we analyzed 32–96 samples (depending on batch size) with both commercial and custom software. We assessed the accuracy of heterozygote detection and homozygote differentiation of a difficult, nearest-neighbor symmetric, class 4 variant with predicted ΔTm of 0.00 °C.

RESULTS

Overall, the heterozygote accuracy was 99.7% (n = 2141), whereas homozygote accuracy was 70.3% (n = 4441). Instruments with single sample detection as opposed to full-plate imaging better distinguished homozygotes (78.1% and 61.8%, respectively, χ2P < 0.0005). Custom software improved accuracy over commercial software (P < 0.002), although melting protocols recommended by manufacturers were better than a constant ramp rate of 0.1 °C with an oil overlay. PCR products of 51, 100, 272, and 547 bp had accuracies of 72.3%, 83.1%, 59.8%, and 65.9%, respectively (P < 0.0005).

CONCLUSIONS

High-resolution melting detects heterozygotes with excellent accuracy, but homozygote accuracy is dependent on detection mode, analysis software, and PCR product size, as well as melting temperature differences between, and variation within, homozygotes.
Determination of the map of efficiency of the Jagiellonian Positron Emission Tomograph (J-PET) detector with the GATE package
Authors: Kowalski Paweł , Raczyński Lech , Bednarski Tomasz , Białas Piotr , Czerwiński Eryk , Giergiel Krzysztof , Kapłon Łukasz , Kochanowski Andrzej , Korcyl Grzegorz , Kowal Jakub , Kozik Tomasz , Krzemień Wojciech , Molenda Marcin , Moskal Ines , Moskal Paweł , Niedźwiecki Szymon , Pałka Marek , Pawlik-Niedźwiecka Monika , Rudy Zbigniew , Salabura Piotr , Sharma Neha , Silarski Michał , Słomski Artur , Smyrski Jerzy , Strzelecki Adam , Szymański Konrad , Wiślicki Wojciech , Witkowski Piotr , Zieliński Marcin , Zoń Natalia
Published: April 2014

A novel PET detector consisting of strips of polymer scintillators is being developed by the Jagiellonian Positron Emission Tomograph (J-PET) collaboration. The map of efficiency and the map of geometrical acceptance of the two-strip J-PET scanner are presented. The map of efficiency was determined using the Monte Carlo simulation software GEANT4 Application for Tomographic Emission (GATE), which is based on GEANT4. Both maps were compared using a method based on the χ2-test.
Cardiovascular therapy through nanotechnology – how far are we still from bedside?
Authors: Cicha Iwona , Garlichs Christoph D. , Alexiou Christoph
Published: April 2014

Recent years brought about a widespread interest in the potential applications of nanotechnology for the diagnostics and the therapy of human diseases. With its promise of disease-targeted, patient-tailored treatment and reduced side effects, nanomedicine brings hope for millions of patients suffering of non-communicable diseases such as cancer or cardiovascular disorders. However, the emergence of the complex, multicomponent products based on new technologies poses multiple challenges to successful approval in clinical practice. Regulatory and development considerations, including properties of the components, reproducible manufacturing and appropriate characterization methods, as well as nanodrugs’ safety and efficacy are critical for rapid marketing of the new products. This review discusses the recent advances in cardiovascular applications of nanotechnologies and highlights the challenges that must be overcome in order to fill the gap existing between the promising bench trials and the successful bedside applications.
Compression properties of vascular boundles and parenchyma of rattan (Plectocomia assamica Griff)
Authors: Liu Xing’e , Tian Genlin , Shang Lili , Yang Shumin , Jiang Zehui
Published: April 2014

Rattan is a unique unidirectional vascular bundles-reinforced biocomposite with many nodes along its canes. Mechanical compression tests have been performed from rattan samples taken from different parts of the cross section. Compression strength increased with increasing amounts of vascular bundles (VBs) in the tissues was investigated. Samples including the outer ring with many VBs have the highest apparent Young’s modulus of 1.08 GPa and the highest compression strength of 17.6 MPa. However, samples consisting of parenchyma cells had an apparent Young’s modulus of 25 MPa, and the compression strength of 1.81 MPa. The compression properties of core samples improved with increasing amounts of VB. The apparent Young’s modulus and compression strength of a single VB were 730 MPa and 6.87 MPa, respectively, and were calculated according to the rule of mixture of composites.
On the Implications of Essential Heterogeneity for Estimating Causal Impacts Using Social Experiments
Authors: Ravallion Martin
Published: April 2014

The standard model of essential heterogeneity, whereby program take up depends on unobserved costs and benefits of take up, is generalized to allow the source of latent heterogeneity to influence counterfactual outcomes. The standard instrumental variables (IV) estimator is shown to still be preferable to the naïve, ordinary least squares (OLS), estimator for mean impact on the treated. However, under certain conditions, the IV estimate of the overall mean impact will be even more biased than OLS. Examples are given for stylized training, insurance and microcredit schemes.
Optically induced forces in scanning probe microscopy
Authors: Kohlgraf-Owens Dana C. , Sukhov Sergey , Greusard Léo , De Wilde Yannick , Dogariu Aristide
Published: April 2014

Typical measurements of light in the near-field utilize a photodetector such as a photomultiplier tube or a photodiode, which is placed remotely from the region under test. This kind of detection has many draw-backs including the necessity to detect light in the far-field, the influence of background propagating radiation, the relatively narrowband operation of photodetectors which complicates the operation over a wide wavelength range, and the difficulty in detecting radiation in the far-IR and THz. Here we review an alternative near-field light measurement technique based on the detection of optically induced forces acting on the scanning probe. This type of detection overcomes some of the above limitations, permitting true broad-band detection of light directly in the near-field with a single detector. The physical origins and the main characteristics of optical force detection are reviewed. In addition, intrinsic effects of the inherent optical forces for certain operation modalities of scanning probe microscopy are discussed. Finally, we review practical applications of optical force detection of interest for the broader field of the scanning probe microscopy.
Perspectives for the Brazilian residual biomass in renewable chemistry
Authors: Vaz Sílvio
Published: April 2014

The need to change non-renewable raw materials by biomass as an oil substitute has been shown to be a strategic challenge for the 21st century. Chemicals have the highest potential to add value to a vegetable biomass chain because of the importance of conventional chemical industry and fine chemical chemistry for different sectors of the economy; these compounds may be used as building blocks, intermediaries of synthesis, and specialties. This article deals with the economic potential of the usage of residual biomass as a raw material in chemistry, with a special interest in residues from bioenergetic chains (biodiesel and ethanol). It focus on showing a scenario related to the perspectives and challenges for the development of a Brazilian renewable chemistry, considering that Brazil is one of the largest global producers of agro-industrial biomass for several purposes, especially for bioenergy.
The journey through the world of adolescent sleep
Authors: Darchia Nato , Cervena Katerina
Published: April 2014

Sleep-wake patterns and the electroencephalogram (EEG) during sleep undergo fundamental changes during adolescence. Scientific evidence indicates that these changes represent components of an extensive maturational brain remodeling process. Sleep during periods of brain maturation appears to be particularly important for health and behavior. Adolescents’ sleep problems affect their cognitive and psychobehavioral functioning, making insufficient sleep during this developmental stage a significant international health concern. In this review, we summarize some key data concerning developmental changes in sleep behavior and regulation, and the association between sleep EEG changes and brain maturation. This review extends our understanding of adolescent sleep and highlights its significance for healthy development. We discuss the possibility to follow brain maturation and to detect errors in this maturational process by monitoring the developmental sleep EEG changes.
Biological effect of SAR on the human head due to variation of dielectric properties at 1800 and 2450 MHz with different antenna substrate materials
Authors: Faruque Mohammad Rashed Iqbal , Islam Mohammad Tariqul , Ullah Mohammad Habib
Published: April 2014

The aim of this study was to consider a possible discrepancy in electromagnetic (EM) absorption in the human head. The finite-difference time-domain (FDTD) method with the lossy Drude model was adopted in this study. Here, the permittivity and conductivity of all head tissues were increased from 10% to 20% except when not using the same exposure conditions. Recognizable mobile phone frequencies of 1800 and 2450 MHz were studied in this simulation. The increase of up to 20% in conductivity and permittivity and varied substrate material always caused an EM absorption variation of 32.59% for specific absorption rate (SAR) 1 g and 35.25% for SAR 10 g at 1800 MHz, and variation of 20.37% for SAR 1 g and 17.99% for SAR 10 g at 2450 MHz, respectively.
A Family of Nonclassical Class I MHC Genes Contributes to Ultrasensitive Chemodetection by Mouse Vomeronasal Sensory Neurons
Authors: Leinders-Zufall Trese , Ishii Tomohiro , Chamero Pablo , Hendrix Philipp , Oboti Livio , Schmid Andreas , Kircher Sarah , Pyrski Martina , Akiyoshi Sachiko , Khan Mona , Vaes Evelien , Zufall Frank , Mombaerts Peter
Published: April 2014

The mouse vomeronasal organ (VNO) has a pivotal role in chemical communication. The vomeronasal sensory neuroepithelium consists of distinct populations of vomeronasal sensory neurons (VSNs). A subset of VSNs, with cell bodies in the basal part of the basal layer, coexpressVmn2rG-protein-coupled receptor genes withH2-Mvgenes, a family of nine nonclassical class I major histocompatibility complex genes. Thein vivo, physiological roles of theH2-Mvgene family remain mysterious more than a decade after the discovery of combinatorialH2-Mvgene expression in VSNs. Here, we have taken a genetic approach and have deleted the 530 kb cluster ofH2-Mvgenes in the mouse germline by chromosome engineering. Homozygous mutant mice (ΔH2Mv mice) are viable and fertile. There are no major anatomical defects in their VNO and accessory olfactory bulb (AOB). Their VSNs can be stimulated with chemostimuli (peptides and proteins) to the same maximum responses as VSNs of wild-type mice, but require much higher concentrations. This physiological phenotype is displayed at the single-cell level and is cell autonomous: single V2rf2-expressing VSNs, which normally coexpressH2-Mvgenes, display a decreased sensitivity to a peptide ligand in ΔH2Mv mice, whereas single V2r1b-expressing VSNs, which do not coexpressH2-Mvgenes, show normal sensitivity to a peptide ligand in ΔH2Mv mice. Consistent with the greatly decreased VSN sensitivity, ΔH2Mv mice display pronounced deficits in aggressive and sexual behaviors. Thus,H2-Mvgenes are not absolutely essential for the generation of physiological responses, but are required for ultrasensitive chemodetection by a subset of VSNs.
Snail Coordinately Regulates Downstream Pathways to Control Multiple Aspects of Mammalian Neural Precursor Development
Authors: Zander Mark A. , Burns Sarah E. , Yang Guang , Kaplan David R. , Miller Freda D.
Published: April 2014

The Snail transcription factor plays a key role in regulating diverse developmental processes but is not thought to play a role in mammalian neural precursors. Here, we have examined radial glial precursor cells of the embryonic murine cortex and demonstrate that Snail regulates their survival, self-renewal, and differentiation into intermediate progenitors and neurons via two distinct and separable target pathways. First, Snail promotes cell survival by antagonizing a p53-dependent death pathway because coincident p53 knockdown rescues survival deficits caused by Snail knockdown. Second, we show that the cell cycle phosphatase Cdc25b is regulated by Snail in radial precursors and that Cdc25b coexpression is sufficient to rescue the decreased radial precursor proliferation and differentiation observed upon Snail knockdown. Thus, Snail acts via p53 and Cdc25b to coordinately regulate multiple aspects of mammalian embryonic neural precursor biology.
A Physiological Signal That Prevents Motor Skill Improvements during Consolidation
Authors: Tunovic Sanjin , Press Daniel Z. , Robertson Edwin M.
Published: April 2014

Different memories follow different processing pathways. For example, some motor skill memories are enhanced over wakefulness, whereas others are instead enhanced over sleep. The processing pathway that a motor skill memory follows may be determined by functional changes within motor circuits. We tested this idea using transcranial magnetic stimulation to measure corticospinal excitability at 6, 21, 36, 96, and 126 min after participants learnt tasks that either were or were not enhanced over wakefulness. There was no change in corticospinal excitability after learning a motor skill that was subsequently enhanced; whereas, there was a substantial transient decrease in corticospinal excitability after learning a motor skill that was not enhanced. In subsequent experiments, we abolished the decrease in corticospinal excitability by applying theta burst stimulation to either the dorsolateral prefrontal or primary motor cortex, and induced motor skill improvements during consolidation. The motor skill improvements in each experiment were correlated with the corticospinal excitability after learning. Together, these experiments suggest that corticospinal excitability changes act as a physiological signal, which prevents improvements from developing over wakefulness, and so when this signal is abolished improvements are induced. Our observations show that the human brain can actively prevent the processing of memories, and provides insights into the mechanisms that control the fate of memories.
ArfGAP3 Is a Component of the Photoreceptor Synaptic Ribbon Complex and Forms an NAD(H)-Regulated, Redox-Sensitive Complex with RIBEYE That Is Important for Endocytosis
Authors: Dembla Mayur , Wahl Silke , Katiyar Rashmi , Schmitz Frank
Published: April 2014

Ribbon synapses are tonically active synapses in the retina and inner ear with intense vesicle traffic. How this traffic is organized and regulated is still unknown. Synaptic ribbons, large presynaptic structures associated with numerous synaptic vesicles, appear to be essential for this process. The base of the synaptic ribbon is anchored at the active zone and is a hotspot of exocytosis. The synaptic ribbon complex is also important for vesicle replenishment. RIBEYE is a unique and major component of synaptic ribbons. It consists of a unique A-domain and an NAD(H)-binding, C-terminal B-domain. In the present study, we show that the Arf-GTPase activating protein-3 (ArfGAP3), a well characterized regulator of vesicle formation at the Golgi apparatus, is also a component of the synaptic ribbon complex in photoreceptor synapses of the mouse retina and interacts with RIBEYE as shown by multiple, independent approaches. ArfGAP3 binds to RIBEYE(B)-domain in an NAD(H)-dependent manner. The interaction is redox sensitive because NADH is more efficient than the oxidized NAD+in promoting ArfGAP3-RIBEYE interaction. RIBEYE competes with the GTP-binding protein Arf1 for binding to ArfGAP3. Thus, binding of RIBEYE(B) to ArfGAP3 could prevent inactivation of Arf1 by ArfGAP3 and provides the synaptic ribbon with the possibility to control Arf1 function. The interaction is relevant for endocytic vesicle trafficking because overexpression of ArfGAP3 in photoreceptors strongly inhibited endocytotic uptake of FM1–43.
Dissecting Integrin-Dependent Regulation of Neural Stem Cell Proliferation in the Adult Brain
Authors: Porcheri Cristina , Suter Ueli , Jessberger Sebastian
Published: April 2014

Controlling neural stem and progenitor cell (NSPC) proliferation is critical to maintain neurogenesis in the mammalian brain throughout life. However, it remains poorly understood how niche-derived cues such as β1-integrin-mediated signaling are translated into NSPC-intrinsic molecular changes to regulate NSPC activity. Here we show that genetic deletion of integrin-linked kinase (ILK) increases NSPC proliferation through PINCH1/2-dependent enhancement of c-Jun N-terminal protein kinase activity in both neurogenic regions of the adult mouse brain. This effect downstream of ILK signaling is mediated through loss of Ras suppressor unit-1 (RSU-1), as virus-based reconstitution of RSU-1 expression rescued the ILK-dependent effects on NSPC proliferation. Thus, we here identified an intracellular signaling cascade linking extrinsic integrin-mediated signaling to NSPC proliferation and characterized a novel mechanism that regulates NSPC activity in the adult mammalian brain.
Slow-Wave Sleep-Imposed Replay Modulates Both Strength and Precision of Memory
Authors: Barnes Dylan C. , Wilson Donald A.
Published: April 2014

Odor perception is hypothesized to be an experience-dependent process involving the encoding of odor objects by distributed olfactory cortical ensembles. Olfactory cortical neurons coactivated by a specific pattern of odorant evoked input become linked through association fiber synaptic plasticity, creating a template of the familiar odor. In this way, experience and memory play an important role in odor perception and discrimination. In other systems, memory consolidation occurs partially via slow-wave sleep (SWS)-dependent replay of activity patterns originally evoked during waking. SWS is ideal for replay given hyporesponsive sensory systems, and thus reduced interference. Here, using artificial patterns of olfactory bulb stimulation in a fear conditioning procedure in the rat, we tested the effects of imposed post-training replay during SWS and waking on strength and precision of pattern memory. The results show that imposed replay during post-training SWS enhanced the subsequent strength of memory, whereas the identical replay during waking induced extinction. The magnitude of this enhancement was dependent on the timing of imposed replay relative to cortical sharp-waves. Imposed SWS replay of stimuli, which differed from the conditioned stimulus, did not affect conditioned stimulus memory strength but induced generalization of the fear memory to novel artificial patterns. Finally, post-training disruption of piriform cortex intracortical association fiber synapses, hypothesized to be critical for experience-dependent odor coding, also impaired subsequent memory precision but not strength. These results suggest that SWS replay in the olfactory cortex enhances memory consolidation, and that memory precision is dependent on the fidelity of that replay.
EJE PRIZE 2014: Current and evolving treatment options in adrenocortical carcinoma: where do we stand and where do we want to go?
Authors: Ronchi Cristina L , Kroiss Matthias , Sbiera Silviu , Deutschbein Timo , Fassnacht Martin
Published: April 2014

Adrenocortical carcinoma (ACC) is not only a rare and heterogeneous disease but also one of the most aggressive endocrine tumors. Despite significant advances in the last decade, its pathogenesis is still only incompletely understood and overall therapeutic means are unsatisfactory. Herein, we provide our personal view of the currently available treatment options and suggest the following research efforts that we consider timely and necessary to improve therapy: i) for better outcome in localized ACCs, surgery should be restricted to experienced centers, which should then collaborate closely to address the key surgical questions (e.g. best approach and extent of surgery) in a multicenter manner. ii) For the development of better systemic therapies, it is crucial to elucidate the exact molecular mechanisms of action of mitotane. iii) A prospective trial is needed to address the role of cytotoxic drugs in the adjuvant setting in aggressive ACCs (e.g. mitotane vs mitotane+cisplatin). iv) For metastatic ACCs, new regimens should be investigated as first-line therapy. v) Several other issues (e.g. the role of radiotherapy and salvage therapies) might be answered – at least in a first step – by large retrospective multicenter studies. In conclusion, although it is unrealistic to expect that the majority of ACCs can be cured within the next decade, international collaborative efforts (including multiple translational and clinical studies) should allow significant improvement of clinical outcome of this disease. To this end, it might be reasonable to expand the European Network for the Study of Adrenal Tumors (ENSAT) to a truly worldwide international network – INSAT.
Construction on the Green function for Vallee-Poussin problem for nonlinear system of differential equations
Authors: Sobkovich R.I. , Kazmerchuk A.I.
Published: April 2014

Existence and uniqueness theorems of solution of n-point Vallee-Poussin problem for system of nonlinear differential equations are proved. Iterative schemes for finding them are proposed.
Conjugacy growth in branch groups
Authors: Bondarenko I.V.
Published: April 2014

We prove that branch groups of automorphisms of regular rooted trees can not have polynomial conjugacy growth.
Aggregation-iterative analogues and generalizations of projection-iterative methods
Authors: Shuvar B.A. , Obshta A.F. , Kopach M.I.
Published: April 2014

Aggregation-iterative algorithms for linear operator equations are constructed and investigated. These algorithms cover methods of iterative aggregation and projection-iterative methods. In convergence conditions there is neither requirement for the corresponding operator of fixed sign no restriction to the spectral radius to be less than one.
Integral mean of Green’s potentials and their conjugate
Authors: Vasyl'kiv Ya.V. , Kravec M.Ya.
Published: April 2014

The best possible estimates for Lebesgue integral means $m_q(r,F)\; (1\le q<+\infty)$ for the pair of functions $F= g+i\:\breve{g}$, here $g$ - Green's potential, $\breve{g}$ - function conjugate to $g$, was obtained. It generalizes well-known results of Ya.V. Vasyl'kiv and A.A. Kondratyuk for logarithms $\log\; B$ of Blaschke products $B$ in terms of counting function $n(r,0,B)\; (0<r<1)$ of their zeroes.
On bidual bases in the space of symmetric analytic functions on $\ell_1$
Authors: Holubchak O.M. , Zagorodnyuk A.V.
Published: April 2014

We consider a special Hilbert space of symmetric analytic functions on $l_1$ and construct a pair of bidual bases of polynomials.
Зростання канонічних добутків Вейєрштрасса нульового роду з випадковими нулями
Authors: Zakharko Yu.B. , Filevych P.V.
Published: April 2014

Нехай $\zeta=(\zeta_n)$ - комплексна послідовність нульового роду з показником збіжності $\tau$, $N(r)$ - її усереднена лічильна функція, $\pi(z)=\prod\bigl(1-\frac{z}{\zeta_n}\bigr)$ - канонічний добуток Вейєрштрасса, а $M(r)$ - максимум модуля цього добутку. Відомо, що тоді виконується нерівність Валунда-Валірона$$\limsup_{r\to+\infty}\frac{N(r)}{\ln M(r)}\ge w(\tau),\qquad w(\tau):=\frac{\sin\pi\tau}{\pi\tau},$$і ця нерівність є точною. В роботі доведено, що для більшості (у ймовірнісному сенсі) послідовностей $\zeta$ сталу $w(\tau)$ в нерівності Валунда-Валірона можна замінити сталою $w\left(\frac{\tau}2\right)$.
Hypercyclic operators on spaces of block-symmetric analytic functions
Authors: Kravtsiv V.V. , Mozhyrovska Z.G. , Zagorodnyuk A.V.
Published: April 2014

The paper contains proof of the hypercyclicity of “symmetric translation” on the algebras of block-symmetric analytic functions of bounded type on an isomorphic copy of $l_1$.
On diameters estimations of the commuting graphs of Sylow $p$-subgroups of the symmetric groups
Authors: Leshchenko Yu.Yu. , Zoria L.V.
Published: April 2014

The commuting graph of a group $G$ is an undirected graph whose vertices are non-central elements of $G$ and two distinct vertices $x,y$ are adjacent if and only if $xy=yx$. This article deals with the properties of the commuting graphs of Sylow $p$-subgroups of the symmetric groups. We define conditions of connectedness of respective graphs and give estimations of the diameters if graph is connected.
First-order linear partial differential equations in the class of separately differentiable functions
Authors: Myronyk V.I. , Mykhaylyuk V.V.
Published: April 2014

It is obtained a general solution of first-order linear partial differential equations in the class of separately differentiable functions.
On the Kolyvagin's formula, the Tate pairing associated to an isogeny, the local Artin map and the Hilberts symbol
Authors: Nesteruk V.I.
Published: April 2014

A proof of nondegeneracy of the Tate pairing and Kolyvagin's formula for elliptic curves with good reductions over an $n$-dimensional $(n\leq 3)$ pseudolocal field, the Tate pairing associated to an isogeny between abelian varieties over pseudolocal field and an $n$-dimensional $(n\leq 3)$ pseudolocal field, and the relations of local Artin map and of the Hilbert symbol for an $n$-dimensional $(n\leq 3)$ general local field is given.
Дифузiї, породженi вiнеровим процесом
Authors: Bigun G.S. , Osypchuk M.M.
Published: April 2014

У роботi розглядається питання можливостi побудови дифузiйного процесу в $\mathbb R^m$ шляхом перетворення вiнерового процесу. Застосовуються гладке перетворення фазового простору та випадкова замiна часу з допомогою адитивного функцiоналу iнтегрального типу.
Оцінки швидкості збіжності 1-періодичного гіллястого ланцюгового дробу спеціального вигляду
Authors: Bubniak M.M.
Published: April 2014

Встановлено оцінки швидкості збіжності 1-періодичного гіллястого ланцюгового дробу спеціального вигляду при умовах: якщо один елемент дробу належить комплексній площині з розрізом ($-\infty; -1/4$], а сума модулів інших елементів обмежена деяким числом; а також, якщо елементи належать відповідним параболічним областям чи об'єднанню цих  областей, a модулі елементів, починаючи з другого, обемежені
On geometric extension of polynomials on Banach spaces
Authors: Verkalets N.B. , Zagorodnyuk A.V.
Published: April 2014

We consider some questions related to Aron-Berner extensions of polynomials on infinitely dimensional complex Banach spaces, using natural extensions of their zeros.
Топологiзацiя простору нарiзно неперервних функцiй
Authors: Voloshyn H.A. , Maslyuchenko V.K.
Published: April 2014

Тут ми вводимо локально опуклу топологію $\mathcal{T}$ пошарової рівномірної збіжності на просторі $S=CC[0,1]^2$ всіх нарізно неперервних функцій $f: [0,1]^2\rightarrow \mathbb{R}$, доводимо, що простір $(S, \mathcal{T})$ повний, неметризовний і що простір $P$ всіх многочленів від двох змінних на $[0,1]^2$ всюди щільний в $S$, отже, $S$ — сепарабельний.
Про одну оцінку $R$-типу цілого ряду Діріхле та її точність
Authors: Hlova T.Ya. , Filevych P.V.
Published: April 2014

Нехай $(\lambda_n)$ $-$ невід'ємна зростаюча до $+\infty$ послідовність, $\tau=\limsup\limits_{n\to\infty}\frac{\ln n}{\lambda_n}$, а $\rho$ $-$ додатне число. З класичної теореми Ж. Валірона випливає, що для кожного цілого ряду Діріхле вигляду $F(s)=\sum a_ne^{s\lambda_n}$ правильна оцінка$$\limsup_{\sigma\to+\infty}\frac{\ln \sup\{|F(s)|:\,\text{Re}\, s=\sigma\}}{e^{\rho\sigma}}\le e^{\rho\tau} \limsup_{n\to\infty}\frac{\lambda_n}{e\rho}|a_n|^\frac{\rho}{\lambda_n}.$$В роботі доведено точність цієї оцінки.
New integral functions generated by rising factorial powers
Authors: Goy T.P. , Zatorsky R.A.
Published: April 2014

We consider new nonelementary functions such as the Fresnel integrals, generated by rising factorial powers. Graphs of such functions are plotted and some of their properties are proved. It is shown, that new integral functions are solutions of second order ordinary differential equations with variable coefficients.
Positive definite branched continued fractions of special form
Authors: Dmytryshyn R.I.
Published: April 2014

Research of the class of branched continued fractions of special form, whose denominators do not equal to zero, is proposed and the connection of such fraction with a certain quadratic form is established. It furnishes new opportunities for the investigation of convergence of branching continued fractions of special form.
Про деякi зв’язанi мiж собою перелiковi задачi
Authors: Zatorsky R.A. , Pylypiv V.M. , Gulka S.
Published: April 2014

Робота присвячена перелiченню розбиттiв деяких класiв мультимножин, $n$-вершинних регулярних графiв другого степеня та бiтрансверсалей $n$-го порядку.
Перiодичнi розв’язки у просторi Соболєва для рiвняння iз частинними похiдними, коефiцiєнти якого залежать вiд параметра
Authors: Il'kiv V.S. , Savka I.Ya. , Symotyuk M.M.
Published: April 2014

Встановлено умови iснування та єдиностi перiодичного розв’язку у просторi Соболєва для лiнiйного рiвняння iз частинними похiдними зi сталими комплексними коефiцiєнтами, що залежать вiд одного дiйсного параметра. Показано, що цi умови виконуються для майже всiх за мiрою Лебеґа значень параметра.
Регулярність розв'язків крайових задач для дифузійно-хвильового рівняння з узагальненими функціями в правих частинах
Authors: Lopushansky A.O.
Published: April 2014

Доведено однозначну розв'язність першої крайової задачі для рівняння$$u^{(\beta)}_t-a(t)u_{xx}=F(x,t), \;\;\; (x,t) \in(0,l)\times (0,T]$$з дробовою похідною $u^{(\beta)}_t$Рімана-Ліувілля порядку $\beta\in (0,2)$, додатним гладким коефіцієнтом $a(t)$, узагальненими функціями в правих частинахта та встановлено деякі достатні умови регулярності його розв'язку за змінною $t$.
Про стабiлiзацiю iнтеграла Пуассона ультрапараболiчних рiвнянь
Authors: Malytska H.P. , Burtnyak I.V.
Published: April 2014

Дослiджується стабiлiзацiя iнтеграла Пуассона для рiвнянь типу Колмогорова, що мають три групи змiнних, за якими є виродження параболiчностi.
Зауваження до достатнiх умов належностi аналiтичних функцiй до класiв збiжностi
Authors: Mulyava O.M. , Sheremeta M.M.
Published: April 2014

Добре відомо, що якщо тейлорові коефіцієнти $f_k$ цілої функції $f$ задовольняють умови $|f_k|/|f_{k+1}|\nearrow+\infty$ при $k\to\infty$ і $\sum\limits_{n=1}^{\infty}|f_k|^{k/\varrho}<+\infty$, то $f$ належить до валіронового класу збіжності. Доведено, що у цьому твердженні умову $|f_k|/|f_{k+1}|\nearrow+\infty$ можна замінити умовою $(l_{k-1}l_{k+1}/l^2_k)|f_k|/|f_{k+1}\nearrow+\infty$, де додатна послідовність $(l_k)$ така, що $\root{k}\of{l_k/l_{k+1}}\asymp 1$ при $k\to\infty$. Подібні результати отримано для інших класів збіжності цілих та аналітичних в одиничному крузі функцій.
Lower bounds on the orders of subgroups connected with Agrawal conjecture
Authors: Popovych R.
Published: April 2014

Explicit lower bounds are obtained on the multiplicative orders of subgroups of a finite field connected with primality proving algorithm.
Reconstruction of energy-dependent Sturm-Liouville equations from two spectra. II
Authors: Pronska N.I.
Published: April 2014

We study the problem of reconstruction of singular energy-dependent Sturm-Liouville equation from two spectra. We suggest a new method of solving this inverse problem by establishing its connection with the problem of reconstruction from one spectrum and the set of norming constants.
Простір цілих рядів Діріхле
Authors: Fedynyak S.I.
Published: April 2014

Вивчається простір цілих рядів Діріхле довільного зростання, на якому задано певну топологію. Показано, що він є простором Фреше.