bluuebunny/crossref_metadata_2025 huggingface dataset:
A gaseous proportional counter built from a conventional aluminum beverage can
Authors: Winkler Alexander , Karadzhinova Aneliya , Hildén Timo , Garcia Francisco , Fedi Giacomo , Devoto Francesco , Brücken Erik J.
Published: July 2015

The gaseous proportional counter is a device that can be used to detect ionizing radiation. These devices can be as simple as a cylindrical cathode and a very thin anode wire centered along its axis. By applying a high voltage, a strong electric field is generated close to the anode wire. Ion-pairs, generated by passing ionizing radiation, create avalanches once they drift into the strong electric field region near the anode. The electrical charges created by the avalanche generate an observable signal which is proportional to the energy loss of the incoming radiation. We discuss the construction of such a device. Our detector was built from an ordinary aluminum beverage can and uses a common electric wire strand as the anode. The construction of this detector offers students at universities or technically oriented high schools a detailed understanding of the design and operation of gaseous radiation detectors. The equipment required to complete the project should be available at most institutions.
Predicting the timing of dynamic events through sound: Bouncing balls
Authors: Gygi Brian , Giordano Bruno L. , Shafiro Valeriy , Kharkhurin Anatoliy , Zhang Peter Xinya
Published: July 2015

Dynamic information in acoustical signals produced by bouncing objects is often used by listeners to predict the objects’ future behavior (e.g., hitting a ball). This study examined factors that affect the accuracy of motor responses to sounds of real-world dynamic events. In experiment 1, listeners heard 2–5 bounces from a tennis ball, ping-pong, basketball, or wiffle ball, and would tap to indicate the time of the next bounce in a series. Across ball types and number of bounces, listeners were extremely accurate in predicting the correct bounce time (CT) with a mean prediction error of only 2.58% of the CT. Prediction based on a physical model of bouncing events indicated that listeners relied primarily on temporal cues when estimating the timing of the next bounce, and to a lesser extent on the loudness and spectral cues. In experiment 2, the timing of each bounce pattern was altered to correspond to the bounce timing pattern of another ball, producing stimuli with contradictory acoustic cues. Nevertheless, listeners remained highly accurate in their estimates of bounce timing. This suggests that listeners can adopt their estimates of bouncing-object timing based on acoustic cues that provide most veridical information about dynamic aspects of object behavior.
Genomic evidence for the Pleistocene and recent population history of Native Americans
Authors: Raghavan Maanasa , Steinrücken Matthias , Harris Kelley , Schiffels Stephan , Rasmussen Simon , DeGiorgio Michael , Albrechtsen Anders , Valdiosera Cristina , Ávila-Arcos María C. , Malaspinas Anna-Sapfo , Eriksson Anders , Moltke Ida , Metspalu Mait , Homburger Julian R. , Wall Jeff , Cornejo Omar E. , Moreno-Mayar J. Víctor , Korneliussen Thorfinn S. , Pierre Tracey , Rasmussen Morten , Campos Paula F. , Damgaard Peter de Barros , Allentoft Morten E. , Lindo John , Metspalu Ene , Rodríguez-Varela Ricardo , Mansilla Josefina , Henrickson Celeste , Seguin-Orlando Andaine , Malmström Helena , Stafford Thomas , Shringarpure Suyash S. , Moreno-Estrada Andrés , Karmin Monika , Tambets Kristiina , Bergström Anders , Xue Yali , Warmuth Vera , Friend Andrew D. , Singarayer Joy , Valdes Paul , Balloux Francois , Leboreiro Ilán , Vera Jose Luis , Rangel-Villalobos Hector , Pettener Davide , Luiselli Donata , Davis Loren G. , Heyer Evelyne , Zollikofer Christoph P. E. , Ponce de León Marcia S. , Smith Colin I. , Grimes Vaughan , Pike Kelly-Anne , Deal Michael , Fuller Benjamin T. , Arriaza Bernardo , Standen Vivien , Luz Maria F. , Ricaut Francois , Guidon Niede , Osipova Ludmila , Voevoda Mikhail I. , Posukh Olga L. , Balanovsky Oleg , Lavryashina Maria , Bogunov Yuri , Khusnutdinova Elza , Gubina Marina , Balanovska Elena , Fedorova Sardana , Litvinov Sergey , Malyarchuk Boris , Derenko Miroslava , Mosher M. J. , Archer David , Cybulski Jerome , Petzelt Barbara , Mitchell Joycelynn , Worl Rosita , Norman Paul J. , Parham Peter , Kemp Brian M. , Kivisild Toomas , Tyler-Smith Chris , Sandhu Manjinder S. , Crawford Michael , Villems Richard , Smith David Glenn , Waters Michael R. , Goebel Ted , Johnson John R. , Malhi Ripan S. , Jakobsson Mattias , Meltzer David J. , Manica Andrea , Durbin Richard , Bustamante Carlos D. , Song Yun S. , Nielsen Rasmus , Willerslev Eske
Published: July 2015

Genetic history of Native Americans

Several theories have been put forth as to the origin and timing of when Native American ancestors entered the Americas. To clarify this controversy, Raghavan
et al.
examined the genomic variation among ancient and modern individuals from Asia and the Americas. There is no evidence for multiple waves of entry or recurrent gene flow with Asians in northern populations. The earliest migrations occurred no earlier than 23,000 years ago from Siberian ancestors. Amerindians and Athabascans originated from a single population, splitting approximately 13,000 years ago.

Science
, this issue
10.1126/science.aab3884
Optimizing sharing of hospital biobank samples
Authors: Riegman Peter H. J. , de Jong Bas , Daidone Maria Grazia , Söderström Tommy , Thompson James , Hall Jacqueline A. , Mendy Maimuna , ten Hoeve Jelle , Broeks Annegien , Reed Wenche , Morente Manuel M. , López-Guerrero José Antonio , Collins V. Peter , Rogan Jane , Ringborg Ulrik
Published: July 2015

Implementing technical guidelines and standards as well as ways to boost cooperation should facilitate sharing of hospital biobank samples.
Fitness cost of antibiotic susceptibility during bacterial infection
Authors: Roux Damien , Danilchanka Olga , Guillard Thomas , Cattoir Vincent , Aschard Hugues , Fu Yang , Angoulvant Francois , Messika Jonathan , Ricard Jean-Damien , Mekalanos John J. , Lory Stephen , Pier Gerald B. , Skurnik David
Published: July 2015

The quest to stem antibiotic resistance might be exacerbated by enhanced fitness and virulence displayed by the drug-resistant microbes.
CRISPR-Cas9-Mediated Genome Editing in Leishmania donovani
Authors: Zhang Wen-Wei , Matlashewski Greg
Published: July 2015

The prokaryotic CRISPR (clustered regularly interspaced short palindromic repeat)-Cas9, an RNA-guided endonuclease, has been shown to mediate efficient genome editing in a wide variety of organisms. In the present study, the CRISPR-Cas9 system has been adapted to
Leishmania donovani
, a protozoan parasite that causes fatal human visceral leishmaniasis. We introduced the Cas9 nuclease into
L. donovani
and generated guide RNA (gRNA) expression vectors by using the
L. donovani
rRNA promoter and the hepatitis delta virus (HDV) ribozyme. It is demonstrated within that
L. donovani
mainly used homology-directed repair (HDR) and microhomology-mediated end joining (MMEJ) to repair the Cas9 nuclease-created double-strand DNA break (DSB). The nonhomologous end-joining (NHEJ) pathway appears to be absent in
L. donovani
. With this CRISPR-Cas9 system, it was possible to generate knockouts without selection by insertion of an oligonucleotide donor with stop codons and 25-nucleotide homology arms into the Cas9 cleavage site. Likewise, we disrupted and precisely tagged endogenous genes by inserting a bleomycin drug selection marker and
GFP
gene into the Cas9 cleavage site. With the use of Hammerhead and HDV ribozymes, a double-gRNA expression vector that further improved gene-targeting efficiency was developed, and it was used to make precise deletion of the 3-kb miltefosine transporter gene (
LdMT
). In addition, this study identified a novel single point mutation caused by CRISPR-Cas9 in
LdMT
(M381T) that led to miltefosine resistance, a concern for the only available oral antileishmanial drug. Together, these results demonstrate that the CRISPR-Cas9 system represents an effective genome engineering tool for
L. donovani.

IMPORTANCE
Leishmania donovani
is the causative agent of fatal visceral leishmaniasis. To understand
Leishmania
infection and pathogenesis and identify new drug targets for control of leishmaniasis, more-efficient ways to manipulate this parasite genome are required. In this study, we have implemented CRISPR-Cas9 genome-editing technology in
L. donovani
. Both single- and dual-gRNA expression vectors were developed using a strong RNA polymerase I promoter and ribozymes. With this system, it was possible to generate loss-of-function insertion and deletion mutations and introduce drug selection markers and the
GFP
sequence precisely into the
L. donovani
genome. These methods greatly improved the ability to manipulate this parasite genome and will help pave the way for high-throughput functional analysis of
Leishmania
genes. This study further revealed that double-stranded DNA breaks created by CRISPR-Cas9 were repaired by the homology-directed repair (HDR) pathway and microhomology-mediated end joining (MMEJ) in
Leishmania
.
Deciphering the Regulatory Circuitry That Controls Reversible Lysine Acetylation in Salmonella enterica
Authors: Hentchel Kristy L. , Thao Sandy , Intile Peter J. , Escalante-Semerena Jorge C.
Published: July 2015

In
Salmonella enterica
, the reversible lysine acetylation (RLA) system is comprised of the protein acetyltransferase (Pat) and sirtuin deacetylase (CobB). RLA controls the activities of many proteins, including the acetyl coenzyme A (acetyl-CoA) synthetase (Acs), by modulating the degree of Acs acetylation. We report that IolR, a
myo
-inositol catabolism repressor, activates the expression of genes encoding components of the RLA system.
In vitro
evidence shows that the IolR protein directly regulates
pat
expression. An
iolR
mutant strain displayed a growth defect in minimal medium containing 10 mM acetate, a condition under which RLA function is critical to control Acs activity. Increased levels of Pat, CobB, or Acs activity reversed the growth defect, suggesting the Pat/CobB ratio in an
iolR
strain is altered and that such a change affects the level of acetylated, inactive Acs. Results of quantitative reverse transcription-PCR (qRT-PCR) analyses of
pat
,
cobB
, and
acs
expression indicated that expression of the genes alluded to in the IolR-deficient strain was reduced 5-, 3-, and 2.6-fold, respectively, relative to the levels present in the strain carrying the

iolR
+

allele. Acs activity in cell-free extracts from an
iolR
mutant strain was reduced ~25% relative to that of the
iolR
+
strain. Glucose differentially regulated expression of
pat
,
cobB
, and
acs
. The catabolite repressor protein (Crp) positively regulated expression of
pat
while having no effect on
cobB
.

IMPORTANCE
Reversible lysine acylation is used by cells of all domains of life to modulate the function of proteins involved in diverse cellular processes. Work reported herein begins to outline the regulatory circuitry that integrates the expression of genes encoding enzymes that control the activity of a central metabolic enzyme in C2 metabolism. Genetic analyses revealed effects on reversible lysine acylation that greatly impacted the growth behavior of the cell. This work provides the first insights into the complexities of the system responsible for controlling reversible lysine acylation at the transcriptional level in the enteropathogenic bacterium
Salmonella enterica
.
An infectious cause of acute kidney injury with low serum potassium
Authors: Cippà Pietro E , Auinger Katja , Wüthrich Rudolf P , Segerer Stephan
Published: July 2015

A 67-year-old man was referred to our hospital because of acute kidney injury, thrombocytopenia and hyperbilirubinemia. Despite severe kidney failure, hypokalemia was present. One infectious cause explained the whole clinical picture.
Impact of cardiovascular comorbidities on COPD Assessment Test (CAT) and its responsiveness to pulmonary rehabilitation in patients with moderate to very severe COPD: protocol of the Chance study
Authors: Smid Dionne E , Wilke Sarah , Jones Paul W , Muris Jean W M , Wouters Emiel F M , Franssen Frits M E , Spruit Martijn A
Published: July 2015

Introduction

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. Patients with COPD are characterised by a reduced health status, which can be easily assessed by the COPD Assessment Test (CAT). Previous studies show that health status can be worsened by the presence of comorbidities. However, the impact of cardiovascular comorbidities on health status as assessed with CAT is not sufficiently investigated. Therefore, the current study has the following objectives: (1) to study the clinical, (patho)physiological and psychosocial determinants of the CAT, and impact of previously established and/or newly diagnosed cardiovascular comorbidities on health status in tertiary care patients with COPD; (2) to assess the effects of pulmonary rehabilitation on CAT scores in patients with COPD; (3) to develop reference values for the CAT in Dutch elderly patients without COPD; and (4) to validate the CAT in a broad sample of Dutch patients with COPD.

Methods and analysis

TheCOPD,Health statusandComorbidities (Chance) study is a monocentre study consisting of an observational cross-sectional part and a longitudinal part. Demographic and clinical characteristics will be assessed in primary care, secondary care and tertiary care patients with COPD, and in patients without COPD. To assess health status, the CAT, Clinical COPD Questionnaire (CCQ) and St George's Respiratory Questionnaire (SGRQ) will be used. The longitudinal part consists of a comprehensive pulmonary rehabilitation programme in 500 tertiary care patients. For the cross-sectional part of the study, 150 patients without COPD, 100 primary care patients and 100 secondary care patients will be assessed during a single home visit.

Ethics and dissemination

The Medical Ethical Committee of the Maastricht University Medical Centre+ (MUMC+), Maastricht, the Netherlands (METC 11-3-070), has approved this study. The study has been registered at the Dutch Trial Register (NTR 3416).
Access to healthcare and financial risk protection for older adults in Mexico: secondary data analysis of a national survey
Authors: Doubova Svetlana V , Pérez-Cuevas Ricardo , Canning David , Reich Michael R
Published: July 2015

Objectives

While the benefits of Seguro Popular health insurance in Mexico relative to no insurance have been widely documented, little has been reported on its effects relative to the pre-existing Social Security health insurance. We analyse the effects of Social Security and Seguro Popular health insurances in Mexico on access to healthcare of older adults, and on financial risk protection to their households, compared with older adults without health insurance.

Setting

Secondary data analysis was performed using the 2012 Mexican Survey of Health and Nutrition (ENSANUT).

Participants

The study population comprised 18 847 older adults and 13 180 households that have an elderly member.

Outcome measures

The dependent variables were access to healthcare given the reported need, the financial burden imposed by health expenditures measured through catastrophic health-related expenditures, and using savings for health-related expenditures. Separate propensity score matching analyses were conducted for each comparison. The analysis for access was performed at the individual level, and the analysis for financial burden at the household level. In each case, matching on a wide set of relevant characteristics was achieved.

Results

Seguro Popular showed a protective effect against lack of access to healthcare for older adults compared with those with no insurance. The average treatment effect on the treated (ATET) was ascertained through using the nearest-neighbour matching (−8.1%, t-stat −2.305) analysis. However, Seguro Popular did not show a protective effect against catastrophic expenditures in a household where an older adult lived. Social Security showed increased access to healthcare (ATET −11.3%, t-stat −3.138), and protective effect against catastrophic expenditures for households with an elderly member (ATET −1.9%, t-stat −2.178).

Conclusions

Seguro Popular increased access to healthcare for Mexican older adults. Social Security showed a significant protective effect against lack of access and catastrophic expenditures compared with those without health insurance.
Tunable laser and photocurrents from linear atomic C chains
Authors: Lin Zheng-Zhe
Published: July 2015

By a tight-binding model, the interaction between linear atomic C chains (LACCs) and short laser pulses was investigated. LACCs were proposed to be used as a medium of laser whose wavelength can be continuously tuned in a range of 321–785[Formula: see text]nm. This data should be more accurate than the previous result [Europhys. Lett. 97 (2012) 27006] because pure density functional theory calculation always underestimates the band gap. According to the tight-binding model, the lifetime of conduction band (CB) bottom is about 1.9–2.3[Formula: see text]ns. The electrons pumped into the CB will quickly fall to the band bottom in a time of ps due to electron–phonon interactions. The above results indicate that LACCs are suitable for laser medium. By [Formula: see text] dichromatic laser pulses, photocurrents can be generated in LACCs, which can be applied as light-controlled signals.
Attosecond XUV sources generation from polarized gating two-color chirped pulse
Authors: Feng Liqiang , Liu Hang , Chu Tianshu
Published: July 2015

A promising method to generate the attosecond XUV sources from the high-order harmonic has been theoretically presented by controlling the polarized gating two-color chirped pulse. The results show that with the introduction of the chirps, the harmonic has been remarkably extended. Moreover, the harmonic interferences are very sensitive to the polarization angle between the two lasers. Particularly, when the polarization angle is equal to [Formula: see text], the supercontinuum with a single quantum path contribution is achieved, and a series of isolated attosecond pulses with the duration of 33 as are directly obtained. Further, by testing the influences of other laser parameters on the supercontinuum, we found that this polarized two-color chirped scheme can also be achieved in the multi-cycle pulse region, which is much better for experimental realization.
Density distribution for the molecules of a liquid in a semi-infinite space
Authors: Molinari Vincenzo , Ganapol Barry D. , Mostacci Domiziano
Published: July 2015

The Sutherland approximation to the van der Waals forces is applied to the derivation of a self-consistent Vlasov-type field in a liquid filling a half space, bordering vacuum. The ensuing Vlasov equation is then derived, and solved to predict the behavior of the density at and in the vicinity of the liquid-vacuum interface. A numerical solution to the Vlasov equation is also produced and the density profile shown and discussed.
HIGH ORDER SPLITTING METHODS FOR FORWARD PDEs AND PIDEs
Authors: ITKIN ANDREY
Published: July 2015

This paper is dedicated to the construction of high order (in both space and time) finite-difference schemes for both forward and backward PDEs and PIDEs, such that option prices obtained by solving both the forward and backward equations are consistent. This approach is partly inspired by Andreassen & Huge (2011) who reported a pair of consistent finite-difference schemes of first-order approximation in time for an uncorrelated local stochastic volatility (LSV) model. We extend their approach by constructing schemes that are second-order in both space and time and that apply to models with jumps and discrete dividends. Taking correlation into account in our approach is also not an issue.
Firm Size and Capital Structure
Authors: Kurshev Alexander , Strebulaev Ilya A.
Published: July 2015

Firm size has been empirically found to be strongly positively related to capital structure. This paper investigates whether a dynamic capital structure model can explain the cross-sectional size–leverage relationship. The driving force that we consider is the presence of fixed costs of external financing that lead to infrequent restructuring and create a wedge between small and large firms. We find four firm-size effects on leverage. Small firms choose higher leverage at the moment of refinancing to compensate for less frequent rebalancings. Their longer waiting times between refinancings lead to lower levels of leverage at the end of restructuring periods. Within one refinancing cycle, the intertemporal relationship between leverage and firm size is negative. Finally, there is a mass of firms opting for no leverage. The analysis of dynamic economy demonstrates that in cross-section, the relationship between leverage and size is positive and thus fixed costs of financing contribute to the explanation of the stylized size–leverage relationship. However, the relationship changes sign when we control for the presence of unlevered firms.
A Methodology to Model the Execution of Communication Software for Accurate Network Simulation
Authors: Kristiansen Stein , Plagemann Thomas , Goebel Vera
Published: July 2015

Network simulation is commonly used to evaluate the performance of distributed systems, but these approaches do not account for the performance impact that protocol execution on nodes has on performance, which can be significant. We provide a methodology to extract from real devices models of communication software execution that can be used to extend network simulators to improve their accuracy. The models are obtained by instrumenting the target devices to obtain the events necessary to describe software execution. We specify which events must be captured, how to capture them, and how to transform the event traces into models that can be used to extend network simulators. The obtained models are based on high-level abstractions that can be used to describe the execution of a wide range of communication software, and the design principles to extend network simulators are not restricted to any specific network simulator. The same model of communication software execution can be used without modification in all discrete event-based network simulators that are extended according to our principles. The models are represented in a human-readable format that is suitable for modification and can therefore be used to predict how software modifications impact performance. We evaluate our models with two proof-of-concept extensions of Ns-3 that execute the models of two modern smartphones: the Google Nexus One (GN1) and the Nokia N900. We measure the accuracy of our models by comparing results from real experiments with those from simulations with our models and analyze the simulation overhead of our approach.
Measuring Temporal Patterns in Dynamic Social Networks
Authors: Wei Wei , Carley Kathleen M.
Published: July 2015

Given social networks over time, how can we measure network activities across different timesteps with a limited number of metrics? We propose two classes of dynamic metrics for assessing temporal evolution patterns of agents in terms of persistency and emergence. For each class of dynamic metrics, we implement it using three different temporal aggregation models ranging from the most commonly used Average Aggregation Model to more the complex models such as the Exponential Aggregation Model. We argue that the problem of measuring temporal patterns can be formulated using Recency and Primacy effect, which is a concept used to characterize human cognitive processes. Experimental results show that the way metrics model Recency--Primacy effect is closely related to their abilities to measure temporal patterns. Furthermore, our results indicate that future network agent activities can be predicted based on history information using dynamic metrics. By conducting multiple experiments, we are also able to find an optimal length of history information that is most relevant to future activities. This optimal length is highly consistent within a dataset and can be used as an intrinsic metric to evaluate a dynamic social network.
Collaborative Security
Authors: Meng Guozhu , Liu Yang , Zhang Jie , Pokluda Alexander , Boutaba Raouf
Published: July 2015

Security is oftentimes centrally managed. An alternative trend of using collaboration in order to improve security has gained momentum over the past few years. Collaborative security is an abstract concept that applies to a wide variety of systems and has been used to solve security issues inherent in distributed environments. Thus far, collaboration has been used in many domains such as intrusion detection, spam filtering, botnet resistance, and vulnerability detection. In this survey, we focus on different mechanisms of collaboration and defense in collaborative security. We systematically investigate numerous use cases of collaborative security by covering six types of security systems. Aspects of these systems are thoroughly studied, including their technologies, standards, frameworks, strengths and weaknesses. We then present a comprehensive study with respect to their analysis target, timeliness of analysis, architecture, network infrastructure, initiative, shared information and interoperability. We highlight five important topics in collaborative security, and identify challenges and possible directions for future research. Our work contributes the following to the existing research on collaborative security with the goal of helping to make collaborative security systems more resilient and efficient. This study (1) clarifies the scope of collaborative security, (2) identifies the essential components of collaborative security, (3) analyzes the multiple mechanisms of collaborative security, and (4) identifies challenges in the design of collaborative security.
Survey on Broadcast Algorithms for Mobile Ad Hoc Networks
Authors: Ruiz Patricia , Bouvry Pascal
Published: July 2015

Networking at any time and any place paves the way for a large number of possible applications in ad hoc networks, from disaster relief in remote areas to network extension. Thus, for the past decades, many works have been proposed trying to make ad hoc networks a reality. The importance of broadcasting in networking and the broadcast nature of the wireless medium have encouraged researchers to join their efforts on designing efficient dissemination algorithms for Mobile Ad Hoc Networks (MANETs). The many different challenges that MANETs face, such as limited network resources, network partitions, or energy restrictions, gave rise to many different approaches to overcome one or more of those problems. Therefore, literature reveals a huge variety of techniques that have been proposed for efficient message dissemination. In this article, we make an in-depth review of the existing state-of-the-art techniques, as well as propose a new taxonomy that provides a global overview of the most relevant existing algorithms.
Cloud Computing Resource Scheduling and a Survey of Its Evolutionary Approaches
Authors: Zhan Zhi-Hui , Liu Xiao-Fang , Gong Yue-Jiao , Zhang Jun , Chung Henry Shu-Hung , Li Yun
Published: July 2015

A disruptive technology fundamentally transforming the way that computing services are delivered, cloud computing offers information and communication technology users a new dimension of convenience of resources, as services via the Internet. Because cloud provides a finite pool of virtualized on-demand resources, optimally scheduling them has become an essential and rewarding topic, where a trend of using Evolutionary Computation (EC) algorithms is emerging rapidly. Through analyzing the cloud computing architecture, this survey first presents taxonomy at two levels of scheduling cloud resources. It then paints a landscape of the scheduling problem and solutions. According to the taxonomy, a comprehensive survey of state-of-the-art approaches is presented systematically. Looking forward, challenges and potential future research directions are investigated and invited, including real-time scheduling, adaptive dynamic scheduling, large-scale scheduling, multiobjective scheduling, and distributed and parallel scheduling. At the dawn of Industry 4.0, cloud computing scheduling for cyber-physical integration with the presence of big data is also discussed. Research in this area is only in its infancy, but with the rapid fusion of information and data technology, more exciting and agenda-setting topics are likely to emerge on the horizon.
Phosphatase control of 4E-BP1 phosphorylation state is central for glycolytic regulation of retinal protein synthesis
Authors: Gardner Thomas W. , Abcouwer Steven F. , Losiewicz Mandy K. , Fort Patrice E.
Published: July 2015

Control of protein synthesis in insulin-responsive tissues has been well characterized, but relatively little is known about how this process is regulated in nervous tissues. The retina exhibits a relatively high protein synthesis rate, coinciding with high basal Akt and metabolic activities, with the majority of retinal ATP being derived from aerobic glycolysis. We examined the dependency of retinal protein synthesis on the Akt-mTOR signaling and glycolysis using ex vivo rat retinas. Akt inhibitors significantly reduced retinal protein synthesis but did not affect glycolytic lactate production. Surprisingly, the glycolytic inhibitor 2-deoxyglucose (2-DG) markedly inhibited Akt1 and Akt3 activities, as well as protein synthesis. The effects of 2-DG, and 2-fluorodeoxyglucose (2-FDG) on retinal protein synthesis correlated with inhibition of lactate production and diminished ATP content, with all these effects reversed by provision of d-mannose. 2-DG treatment was not associated with increased AMPK, eEF2, or eIF2α phosphorylation; instead, it caused rapid dephosphorylation of 4E-BP1. 2-DG reduced total mTOR activity by 25%, but surprisingly, it did not reduce mTORC1 activity, as indicated by unaltered raptor-associated mTOR autophosphorylation and ribosomal protein S6 phosphorylation. Dephosphorylation of 4E-BP1 was largely prevented by inhibition of PP1/PP2A phosphatases with okadaic acid and calyculin A, and inhibition of PPM1 phosphatases with cadmium. Thus, inhibition of retinal glycolysis diminished Akt and protein synthesis coinciding with accelerated dephosphorylation of 4E-BP1 independently of mTORC1. These results demonstrate a novel mechanism regulating protein synthesis in the retina involving an mTORC1-independent and phosphatase-dependent regulation of 4E-BP1.
UTP activates small-conductance Ca2+-activated K+ channels in murine detrusor PDGFRα+ cells
Authors: Lee Haeyeong , Koh Byoung H. , Yamasaki Evan , George Nikita E. , Sanders Kenton M. , Koh Sang Don
Published: July 2015

Purines induce transient contraction and prolonged relaxation of detrusor muscles. Transient contraction is likely due to activation of inward currents in smooth muscle cells, and prolonged relaxation may be due to activation of small-conductance Ca2+-activated K+ (SK) channels via P2Y1 receptors expressed by detrusor PDGF receptor (PDGFR)α+ cells. We investigated whether other subtypes of P2Y receptors are involved in the activation of SK channels in PDGFRα+ cells of detrusor muscles. Quantitative analysis of transcripts revealed that P2ry2, P2ry4, and P2ry14 are expressed in PDGFRα+ cells of P2ry1-deficient/enhanced green fluorescent protein ( P2ry1−/−/eGFP) mice at similar levels as in wild-type mice. UTP, a P2Y2/P2Y4 agonist, activated large outward currents in detrusor PDGFRα+ cells. SK channel blockers and an inhibitor of phospholipase C completely abolished currents activated by UTP. In contrast, UTP activated nonselective cation currents in smooth muscle cells. Under current-clamp (current = 0), UTP induced significant hyperpolarization of PDGFRα+ cells. MRS2500, a selective P2Y1 antagonist, did not affect UTP-activated outward currents in PDGFRα+ cells from wild-type mice, and activation of outward currents by UTP was retained in P2ry1−/−/eGFP mice. As a negative control, we tested the effect of MRS2693, a selective P2Y6 agonist. This compound did not activate outward currents in PDGFRα+ cells, and currents activated by UTP were unaffected by MRS2578, a selective P2Y6 antagonist. The nonselective P2Y receptor blocker suramin inhibited UTP-activated outward currents in PDGFRα+ cells. Our data demonstrate that P2Y2 and/or P2Y4 receptors function, in addition to P2Y1 receptors, in activating SK currents in PDGFRα+ cells and possibly in mediating purinergic relaxation responses in detrusor muscles.
A recording chamber for small volume slice electrophysiology
Authors: Dondzillo Anna , Quinn Kevin D. , Cruickshank-Quinn Charmion I. , Reisdorph Nichole , Lei Tim C. , Klug Achim
Published: July 2015

Electrophysiological recordings from brain slices are typically performed in small recording chambers that allow for the superfusion of the tissue with artificial extracellular solution (ECS), while the chamber holding the tissue is mounted in the optical path of a microscope to image neurons in the tissue. ECS itself is inexpensive, and thus superfusion rates and volumes of ECS consumed during an experiment using standard ECS are not critical. However, some experiments require the addition of expensive pharmacological agents or other chemical compounds to the ECS, creating a need to build superfusion systems that operate on small volumes while still delivering appropriate amounts of oxygen and other nutrients to the tissue. We developed a closed circulation tissue chamber for slice recordings that operates with small volumes of bath solution in the range of 1.0 to 2.6 ml and a constant oxygen/carbon dioxide delivery to the solution in the bath. In our chamber, the ECS is oxygenated and recirculated directly in the recording chamber, eliminating the need for tubes and external bottles/containers to recirculate and bubble ECS and greatly reducing the total ECS volume required for superfusion. At the same time, the efficiency of tissue oxygenation and health of the section are comparable to standard superfusion methods. We also determined that the small volume of ECS contains a sufficient amount of nutrients to support the health of a standard brain slice for several hours without concern for either depletion of nutrients or accumulation of waste products.
Inducing hindlimb locomotor recovery in adult rat after complete thoracic spinal cord section using repeated treadmill training with perineal stimulation only
Authors: Alluin Olivier , Delivet-Mongrain Hugo , Rossignol Serge
Published: July 2015

Although a complete thoracic spinal cord section in various mammals induces paralysis of voluntary movements, the spinal lumbosacral circuitry below the lesion retains its ability to generate hindlimb locomotion. This important capacity may contribute to the overall locomotor recovery after partial spinal cord injury (SCI). In rats, it is usually triggered by pharmacological and/or electrical stimulation of the cord while a robot sustains the animals in an upright posture. In the present study we daily trained a group of adult spinal (T7) rats to walk with the hindlimbs for 10 wk (10 min/day for 5 days/wk), using only perineal stimulation. Kinematic analysis and terminal electromyographic recordings revealed a strong effect of training on the reexpression of hindlimb locomotion. Indeed, trained animals gradually improved their locomotion while untrained animals worsened throughout the post-SCI period. Kinematic parameters such as averaged and instant swing phase velocity, step cycle variability, foot drag duration, off period duration, and relationship between the swing features returned to normal values only in trained animals. The present results clearly demonstrate that treadmill training alone, in a normal horizontal posture, elicited by noninvasive perineal stimulation is sufficient to induce a persistent hindlimb locomotor recovery without the need for more complex strategies. This provides a baseline level that should be clearly surpassed if additional locomotor-enabling procedures are added. Moreover, it has a clinical value since intrinsic spinal reorganization induced by training should contribute to improve locomotor recovery together with afferent feedback and supraspinal modifications in patients with incomplete SCI.
Experimental Study on the Components in Polyvalent “Ghost” Salmonella Vaccine for Veterinary Use
Authors: Pencheva Daniela Vasileva , Velichkova Elena Ilieva , Sandarov Denis Zdravkov , Cardoso Adrian Draganov , Mileva Maria Hristova , Genova-Kalou Petia Dinkova , Bryaskova Rayna
Published: July 2015

Development of “ghost” Salmonella vaccines, inactivated by using a hybrid nanomaterial based on silver nanoparticles (AgNps) stabilized via polyvinyl alcohol (PVA), is an innovative approach in vaccine production. For this purpose, a series of attempts to establish the components of the polyvalent “ghost” Salmonella vaccine and the most suitable methods for its preparation were performed. The following strains S. Enteritidis, S. Newport‐Puerto Rico, and S. Typhimurium were chosen as appropriate candidates for their incorporation in order to create polyvalent Salmonella “ghost” vaccine for veterinary use.
Review of Ethnobotanical, Phytochemical, and Pharmacological Study ofThymus serpyllumL.
Authors: Jarić Snežana , Mitrović Miroslava , Pavlović Pavle
Published: July 2015

Thymus serpyllumL. (wild thyme) is a perennial shrub, native to areas of northern and central Europe. Its aerial parts are most frequently used in ethnomedicine (mainly for treating illnesses and problems related to the respiratory and gastrointestinal systems), although recently its essential oils are becoming more popular as an important plant-derived product. The composition of these oils is affected by geographic region, the development stage of the plant, the harvest season, habitat, and climatic conditions. Wild thyme essential oil has an ever-growing number of uses in contemporary medicine due to its pharmacological properties: antioxidative, antimicrobial, and anticancerogenic activities. The antioxidative and antimicrobial properties of the essential oil are related to the synergistic and cumulative effect of its components. In terms of antitumor and cytotoxic activity, further research into the effects of essential oil is necessary, aimed at improving its cytotoxic effects, on the basis of which appropriate medicines can be formulated. Due to its pharmacological properties, the essential oil of wild thyme, a plant used in traditional medicine, represents an important natural resource for the pharmaceutical industry. In addition, it can be a source of natural antioxidants, nutritional supplements, or components of functional foods in the food industry.
An Efficient Hybrid Conjugate Gradient Method with the Strong Wolfe-Powell Line Search
Authors: Alhawarat Ahmad , Mamat Mustafa , Rivaie Mohd , Salleh Zabidin
Published: July 2015

Conjugate gradient (CG) method is an interesting tool to solve optimization problems in many fields, such as design, economics, physics, and engineering. In this paper, we depict a new hybrid of CG method which relates to the famous Polak-Ribière-Polyak (PRP) formula. It reveals a solution for the PRP case which is not globally convergent with the strong Wolfe-Powell (SWP) line search. The new formula possesses the sufficient descent condition and the global convergent properties. In addition, we further explained about the cases where PRP method failed with SWP line search. Furthermore, we provide numerical computations for the new hybrid CG method which is almost better than other related PRP formulas in both the number of iterations and the CPU time under some standard test functions.
Prognosis of Acute Kidney Injury and Hepatorenal Syndrome in Patients with Cirrhosis: A Prospective Cohort Study
Authors: Allegretti Andrew S. , Ortiz Guillermo , Wenger Julia , Deferio Joseph J. , Wibecan Joshua , Kalim Sahir , Tamez Hector , Chung Raymond T. , Karumanchi S. Ananth , Thadhani Ravi I.
Published: July 2015

Background/Aims. Acute kidney injury is a common problem for patients with cirrhosis and is associated with poor survival. We aimed to examine the association between type of acute kidney injury and 90-day mortality.Methods. Prospective cohort study at a major US liver transplant center. A nephrologist’s review of the urinary sediment was used in conjunction with the 2007 Ascites Club Criteria to stratify acute kidney injury into four groups: prerenal azotemia, hepatorenal syndrome, acute tubular necrosis, or other.Results. 120 participants with cirrhosis and acute kidney injury were analyzed. Ninety-day mortality was 14/40 (35%) with prerenal azotemia, 20/35 (57%) with hepatorenal syndrome, 21/36 (58%) with acute tubular necrosis, and 1/9 (11%) with other (p=0.04overall). Mortality was the same in hepatorenal syndrome compared to acute tubular necrosis (p=0.99). Mortality was lower in prerenal azotemia compared to hepatorenal syndrome (p=0.05) and acute tubular necrosis (p=0.04). Ten participants (22%) were reclassified from hepatorenal syndrome to acute tubular necrosis because of granular casts on urinary sediment.Conclusions. Hepatorenal syndrome and acute tubular necrosis result in similar 90-day mortality. Review of urinary sediment may add important diagnostic information to this population. Multicenter studies are needed to validate these findings and better guide management.
The Fundus Autofluorescence Spectrum of Punctate Inner Choroidopathy
Authors: Li Miaoling , Zhang Xiongze , Wen Feng
Published: July 2015

Purpose. To investigate the fundus autofluorescence (FAF) spectrum of punctate inner choroidopathy (PIC).Methods. This is a retrospective observational case series of 27 consecutive patients with PIC admitted from October 2013 to March 2015, who underwent short-wavelength- (SW-) and near-infrared- (NIR-) FAF imaging, spectral domain optical coherence tomography (SD-OCT), fluorescein angiography (FA), and indocyanine green angiography (ICGA).Results. There were three primary findings on the FAF imaging of patients with PIC. First, active PIC lesions revealed hypoautofluorescent spots with hyperautofluorescent margin. After the lesions regressed, the hyperautoflurescent margin faded. Second, subclinical and most of the atrophic PIC lesions appeared to be hypoautofluorescent spots. But subclinical PIC lesions were more distinctive on NIR-FAF imaging than on SW-FAF imaging. Third, hypoautofluorescent spots of PIC lesions coexisted with hyperautofluorescent patches on SW-FAF imaging. These hyperautofluorescent patches were demonstrated to be multiple evanescent white dot syndrome (MEWDS) or acute zonal occult outer retinopathy (AZOOR) lesions by subsequent multimodal imaging and faded during follow-up examinations.Conclusion. FAF imaging helps in noninvasively tracking the evolution of PIC lesions and identifying the combined MEWDS or AZOOR lesions, complementary to SD-OCT and angiographic studies.
Prognostic Value of FOXM1 in Patients with Malignant Solid Tumor: A Meta-Analysis and System Review
Authors: Dai Jun , Yang Lili , Wang Jinyu , Xiao Ying , Ruan Qiurong
Published: July 2015

Forkhead box M1 (FOXM1), a member of the Fox transcription factors family, was closely related with cell cycle. FOXM1 played an important role in MST and prompted a poor prognosis for MST patients. However, there were also some studies revealing no significant association between the FOXM1 expression and prognosis of patients. Therefore, we conducted meta-analysis to investigate whether the expression of FOXM1 was associated with MST prognosis. We collected 36 relevant studies through PubMed database and obtained research data of 4946 patients. Stata 12.0 was used to express the results as hazard ratio (HR) for time-to-event outcomes with 95% confidence intervals (95% CI). It was shown that overexpression of FOXM1 was relevant to worse survival of MST patients (HR = 1.99, 95% CI = 1.79–2.21,P<0.001;I2=26.4%,Ph=0.076). Subgroup analysis suggested that overexpression of FOXM1 in breast cancer (BC), gastric cancer (GC), hepatocellular carcinoma (HCC), pancreatic ductal adenocarcinoma (PDA), and non-small-cell lung cancer (NSCLC) all predicted a worse survival (P<0.05), in addition to ovarian cancer (OC) (P=0.084). In conclusion, our research indicated that overexpression of FOXM1 was to the disadvantage of the prognosis for majority of MST and therefore can be used as an evaluation index of prognosis.
A Neurologist’s Guide to TNF Biology and to the Principles behind the Therapeutic Removal of Excess TNF in Disease
Authors: Clark Ian A. , Vissel Bryce
Published: July 2015

Tumor necrosis factor (TNF) is an ancient and widespread cytokine required in small amounts for much physiological function. Higher concentrations are central to innate immunity, but if unchecked this cytokine orchestrates much chronic and acute disease, both infectious and noninfectious. While being a major proinflammatory cytokine, it also controls homeostasis and plasticity in physiological circumstances. For the last decade or so these principles have been shown to apply to the central nervous system as well as the rest of the body. Nevertheless, whereas this approach has been a major success in treating noncerebral disease, its investigation and potential widespread adoption in chronic neurological conditions has inexplicably stalled since the first open trial almost a decade ago. While neuroscience is closely involved with this approach, clinical neurology appears to be reticent in engaging with what it offers patients. Unfortunately, the basic biology of TNF and its relevance to disease is largely outside the traditions of neurology. The purpose of this review is to facilitate lowering communication barriers between the traditional anatomically based medical specialties through recognition of shared disease mechanisms and thus advance the prospects of a large group of patients with neurodegenerative conditions for whom at present little can be done.
Study on Sensory Quality, Antioxidant Properties, and Maillard Reaction Products Formation in Rye-Buckwheat Cakes Enhanced with Selected Spices
Authors: Przygodzka Małgorzata , Zieliński Henryk , Ciesarová Zuzana , Kukurová Kristina , Lamparski Grzegorz
Published: July 2015

The effect of selected spices included in the recipe of rye-buckwheat cakes on sensory quality, nutritional value, and Maillard reaction (MR) products formation was addressed in this study. The cakes with cloves, nutmeg, allspice, cinnamon, vanilla, and spice mix addition revealed the highest overall quality values. Cakes enriched with cloves, allspice, and spice mix showed the highest rutin content and almost threefold higher available lysine contents whereas cakes enhanced with mix, cloves, and cinnamon were the richest source of phenolic compounds. The highest antioxidant capacity showed cakes with cloves and spice mix. The furosine, a marker of early stage of MR, was decreased in cakes with cloves, allspice, spice mix, and vanilla whereas fluorescent intermediatory compounds were reduced in cakes enhanced with cloves, allspice, and cinnamon. In contrast, browning index was increased as compared to cakes without spices. The FAST index was significantly lowered in all cakes enriched with spices, especially with cloves, allspice, and mix addition. The presence of cloves, allspice, and vanilla in cake formula was the most efficient in acrylamide strategy. It can be suggested that cloves, allspice, and vanilla might be used for production of safety and good quality cakes.