bluuebunny/crossref_metadata_2025 huggingface dataset:
Outage performance of relay-assisted primary and secondary transmissions in cognitive relay networks
Authors: Zhao Feng , Sun Xiangqi , Chen Hongbin , Bie Rongfang
Published: April 2014

In this paper, a two-phase protocol for relay-assisted spectrum sharing in cognitive relay network is proposed. The primary system comprises a transmitter-receiver pair (PT-PR) and a decode-and-forward relay (Relay), while the secondary system comprises a transmitter-receiver pair (ST-SR). In the proposed protocol, the Relay assists the transmissions of the primary users as well as the secondary users where there is no direct link between the ST and the SR. Outage probabilities of the primary system and the secondary system are derived and verified through simulations. Compared with the protocol without cooperation, better outage performance of the primary system is achieved. Meanwhile, though the ST causes interference to the PR, the interference is compensated by the cooperation of the Relay. Moreover, the proposed protocol realizes the communications of the secondary users on the condition that the secondary transmission link is not ideal.
Protein synthesis and secretion in human mesenchymal cells derived from bone marrow, adipose tissue and Wharton’s jelly
Authors: Amable Paola Romina , Teixeira Marcus Vinicius Telles , Carias Rosana Bizon Vieira , Granjeiro José Mauro , Borojevic Radovan
Published: April 2014

Introduction

Different mesenchymal stromal cells (MSC) have been successfully isolated and expanded in vitro and nowadays they are tested in clinical trials for a wide variety of diseases. Whether all MSC express the same cell surface markers or have a similar secretion profile is still controversial, making it difficult to decide which stromal cell may be better for a particular application.

Methods

We isolated human mesenchymal stromal cells from bone marrow (BM), adipose tissue (AT) and Wharton’s jelly (WJ) and cultured them in fetal bovine serum supplemented media. We evaluated proliferation, in vitro differentiation (osteogenic, adipogenic and chondrogenic potential), expression of cell surface markers and protein secretion using Luminex and ELISA assays.

Results

Cell proliferation was higher for WJ-MSC, followed by AT-MSC. Differences in surface expression markers were observed only for CD54 and CD146. WJ-MSC secreted higher concentrations of chemokines, pro-inflammatory proteins and growth factors. AT-MSC showed a better pro-angiogenic profile and secreted higher amounts of extracellular matrix components and metalloproteinases.

Conclusions

Mesenchymal stromal cells purified from different tissues have different angiogenic, inflammatory and matrix remodeling potential properties. These abilities should be further characterized in order to choose the best protocols for their therapeutic use.
RETRACTED ARTICLE: Umbilical cord tissue-derived mesenchymal stem cells induce apoptosis in PC-3 prostate cancer cells through activation of JNK and downregulation of PI3K/AKT signaling
Authors: Han Ihn , Yun Miyong , Kim Eun-Ok , Kim Bonglee , Jung Min-Hyung , Kim Sung-Hoon
Published: April 2014

Introduction

Although mesenchymal stem cells (MSCs) have antitumor potential in hepatocellular carcinoma and breast cancer cells, the antitumor mechanism of human umbilical cord mesenchymal stem cells (hUCMSCs) in prostate cancer cells still remains unclear. Thus, in the present study, we elucidated the antitumor activity of hUCMSCs in PC-3 prostate cancer cells in vitro and in vivo.

Methods

hUCMSCs were isolated from Wharton jelly of umbilical cord and characterized via induction of differentiations, osteogenesis, and adipogenesis. Antitumor effects of UCMSCs on tumor growth were evaluated in a co-culture condition with PC-3 prostate cancer cells. PC-3 cells were subcutaneously (sc) injected into the left flank of nude mice, and UCMSCs were sc injected into the right flank of the same mouse.

Results

We found that hUCMSCs inhibited the proliferation of PC-3 cells in the co-culture condition. Furthermore, co-culture of hUCMSCs induced the cleavage of caspase 9/3 and PARP, activated c-jun NH2-terminal kinase (JNK), and Bax, and attenuated the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/ AKT, extracellular signal-regulated kinase (ERK), and the expression of survival genes such as Bcl-2, Bcl-xL, Survivin, Mcl-1, and cIAP-1 in PC-3 cells in Western blotting assay. Conversely, we found that treatment of specific JNK inhibitor SP600125 suppressed the cleavages of caspase 9/3 and PARP induced by hUCMSCs in PC-3 cells by Western blotting and immunofluorescence assay. The homing of hUCMSCs to, and TUNEL-positive cells on, the K562 xenograft tumor region were detected in Nu/nu-BALB/c mouse.

Conclusions

These results suggest that UCMSCs inhibit tumor growth and have the antitumor potential for PC-3 prostate cancer treatment.
Effective T helper cell responses against retroviruses: are all clonotypes equal?
Authors: Thorborn Georgina , Young George R , Kassiotis George
Published: April 2014

The critical importance of CD4+ T cells in coordinating innate and adaptive immune responses is evidenced by the susceptibility to various pathogenic and opportunistic infections that arises from primary or acquired CD4+ T cell immunodeficiency, such as following HIV-1 infection. However, despite the clearly defined roles of cytotoxic CD8+ T cells and antibodies in host protection from retroviruses, the ability of CD4+ T cells to exert a similar function remains unclear. Recent studies in various settings have drawn attention to the complexity of the T cell response within and between individuals. Distinct TCR clonotypes within an individual differ substantially in their response to the same epitope. Functionally similar, “public” TCR clonotypes can also dominate the response of different individuals. TCR affinity for antigen directly influences expansion and differentiation of responding T cells, also likely affecting their ultimate protective capacity. With this increasing understanding of the parameters that determine the magnitude and effector type of the T cell response, we are now better equipped to address the protective capacity against retroviruses of CD4+ T cell clonotypes induced by natural infection or vaccination.
Intraspecific scaling of arterial blood pressure in the Burmese python
Authors: Enok Sanne , Slay Christopher , Abe Augusto S. , Hicks James W. , Wang Tobias
Published: April 2014

Interspecific allometric analyses indicate that mean arterial blood pressure (MAP) increases with body mass of snakes and mammals. In snakes, MAP increases in proportion to the increased distance between the heart and the head, when the heart-head vertical distance is expressed a ρgh, and the rise in MAP is associated with larger heart to normalize wall stress in the ventricular wall. Based on measurements of MAP in Burmese python ranging from 0.9-3.7 m in length (0.20-27 kg), we demonstrate that although MAP increases with body mass, the rise in MAP is merely half of that predicted by heart-head distance. Scaling relationships within individual species, therefore, may not be accurately predicted by existing interspecific analyses.
Foot speed, foot-strike and footwear:linking gait mechanics and running ground reaction forces
Authors: Clark Kenneth P. , Ryan Laurence J. , Weyand Peter G.
Published: April 2014

Running performance, energy requirements, and musculoskeletal stresses are directly related to the action-reaction forces between the limb and ground. For human runners, the force-time patterns from individual footfalls can vary considerably across speed, foot-strike, and footwear conditions. Here, we used four human footfalls with distinctly different vertical force-time waveform patterns to evaluate whether a basic mechanical model might explain all of them. Our model partitions the body's total mass (1.0 Mb) into two invariant mass fractions (lower-limb=0.08, remaining body mass=0.92) and allows the instantaneous collisional velocities of the former to vary. The best fits achieved (R2 range: 0.95-0.98, mean=0.97±0.01) indicate that the model is capable of accounting for nearly all of the variability observed in the four waveform types tested: barefoot jog, rear-foot strike run, fore-foot strike run, and fore-foot strike sprint. We conclude that different running ground reaction force-time patterns may have the same mechanical basis.
mRNA degradation: an underestimated factor on steady-state transcript levels of cytochromecoxidase subunits?
Authors: Bremer Katharina , Moyes Christopher D.
Published: April 2014

Steady-state mRNA levels are determined by synthesis and degradation; however, changes in mRNA levels are usually attributed to transcription. For cytochrome c oxidase (COX), cold acclimation typically leads to an increase in COX activity while transcript levels for the nuclear-encoded subunits change non-stoichiometrically. Whether those patterns are caused by differences in subunit transcription rates, decay rates, or both, was not known. We assessed decay rates of transcripts for COX subunits, including representatives that decreased, increased in parallel with COX, or increased in excess of COX. Low temperature reduced the decay rate of all transcripts; however COX subunits displayed higher thermal sensitivity than housekeeping genes. The lower decay rates for COX transcripts might explain some of their increase in response to cold acclimation. The reason for the exaggerated transcript response of two subunits (COX6B-1, COX7A-2) may due to decreased decay. However, decay rate differences could not explain the patterns seen with subunits that did not change in mRNA level with thermal acclimation (COX6A-2). Further, the decay patterns differed between two thermal acclimation experiments, which may explain some of the heterogeneity seen in fish studies. The differences in decay rates suggest that the lack of stoichiometry in mRNA levels is exacerbated by post-transcriptional mechanisms. Collectively, these results suggest that temperature-induced differences in COX subunit mRNA levels and deviations from stoichiometry between them may partially arise from subunit-specific sensitivities to degradation. We suggest all subunits to be controlled by transcription, and exaggerated responses of some subunits to be due to reduced decay rates.
Is there metabolic cold adaptation in terrestrial ectotherms? Exploring a latitudinal compensation using a common garden experiment of the invasive snailCornu aspersum
Authors: Gaitán-Espitia Juan D. , Nespolo Roberto F.
Published: April 2014

Lower temperatures, extreme seasonality and shorter growing seasons at higher latitudes are expected to cause a decline in metabolic rates and annual growth rates of ectotherms. If a reduction in the rates of these biological processes involves a reduction in fitness, then organisms may evolve compensatory responses for the constraints imposed by high-latitude habitats. To test the existence of a latitudinal compensation in ectotherms we used a common garden experiment to investigate the extent to which the level of energy turnover (measured as standard metabolic rate, SMR) and the energy budget (energy allocation to growth) are affected by climatic constraints in three populations of the land snail Cornu aspersum, distributed across a latitudinal gradient of 1300 kms in Chile. Our results did not support the existence of a latitudinal compensation in metabolic rates (Metabolic Cold adaptation). However, there was a countergradient variation (CnGV) for growth rate in which the highest latitudinal population exhibited greater growth rates than their counterparts from lower latitudes. Surprisingly, this CnGV pattern was accompanied by a lower apparent dry-matter digestibility, which could highlight a differential assimilation of ingested nutrients into somatic tissue, revealing enhanced growth efficiency in snails from the highest latitudinal habitat. Our evidence highlights that adjustments in energy allocation to the digestive machinery and to protein storage could act as a latitudinal compensation for enhanced growth efficiency in snails from the highest latitudinal population.
Phase shifts in binaural stimuli provide directional cues for sound localization in the field cricket Gryllus bimaculatus
Authors: Seagraves Kelly , Hedwig Berthold
Published: April 2014

The cricket's auditory system is a highly directional pressure difference receiver whose function is hypothesised to depend on phase relationships between the sound waves propagating through the auditory trachea that connects the left and right hearing organs. We tested this hypothesis by measuring the effect of experimentally constructed phase shifts in acoustic stimuli on phonotactic behavior of G. bimaculatus, the oscillatory response patterns of the tympanic membrane, and the activity of the auditory afferents. The same artificial calling song was played simultaneously at the left and right sides of the cricket, but one sound pattern was shifted in phase by 90° (carrier frequencies between 3.6-5.4 kHz). All three levels of auditory processing are sensitive to experimentally induced acoustic phase shifts, and the response characteristics are dependent on the carrier frequency of the sound stimulus. At lower frequencies crickets steered away from the sound leading in phase, while tympanic membrane vibrations and auditory afferent responses were smaller when the ipsilateral sound was leading. In contrast, at higher frequencies opposite responses were observed in all three levels of auditory processing. Minimal responses occurred near the carrier frequency of the cricket's calling song, suggesting a stability at this frequency. Our results indicate that crickets may use directional cues arising from phase shifts in acoustic signals for sound localization, and that the response properties of pressure difference receivers may be analysed with phase-shifted sound stimuli to further our understanding of how insect auditory systems are adapted for directional processing
The four aldehyde oxidases of Drosophila melanogaster have different gene expression patterns and enzyme substrate specificities
Authors: Marelja Zvonimir , Dambowsky Miriam , Bolis Marco , Georgiou Marina L. , Garattini Enrico , Missirlis Fanis , Leimkühler Silke
Published: April 2014

In the genome of Drosophila melanogaster four genes coding for aldehyde oxidases (AOX1-4) were identified on chromosome 3. Phylogenetic analysis showed that the AOX-gene cluster evolved via independent duplication events in the vertebrate and invertebrate lineages. The functional role and the substrate specificity of the distinct Drosophila AOX enzymes is unknown. Two loss-of-function mutant alleles in this gene region, low pyridoxal oxidase (Polpo) and aldehyde oxidase-1 (Aldox-1n1) are associated with a phenotype characterized by undetectable AOX enzymatic activity. However, the genes involved and the corresponding mutations have not yet been identified. In this study we characterized the activities, substrate specificities and expression profiles of the four AOX enzymes in D. melanogaster. We show that the Polpo associated phenotype is the consequence of a structural alteration of the AOX1 gene. We identified an 11-base-pair deletion in the Polpo allele resulting in a frame-shift event, which removes the molybdenum cofactor domain of the encoded enzyme. Furthermore, we show that AOX2 activity is detectable only during metamorphosis and characterize a Minos-AOX2 insertion in this developmental gene that disrupts its activity. We demonstrate that the Aldox-1n phenotype maps to the AOX3 gene and AOX4 activity is not detectable in our assays.
Oxygen diffusion limitation triggers ventilatory movements during spiracle closure when insects breathe discontinuously
Authors: Huang Shu-Ping , Sender Roi , Gefen Eran
Published: April 2014

During discontinuous gas exchange cycles in insects, spiracular opening follows a typical prolonged period of spiracle closure. Gas exchange with the environment occurs mostly during the period of full spiracular opening. In this study we tested the hypothesis that recently reported ventilatory movements during the spiracle closure period serve to mix the tracheal system gaseous contents, and support diffusive exchanges with the tissues. Using heliox (21% O2, 79% N2), we found that by increasing oxygen diffusivity in the gas-phase, ventilatory movements were significantly delayed compared to normoxic conditions. Exposure to hyperoxic conditions (40% O2 in nitrogen) resulted in a similar delay in forced ventilation. Together, these results indicate that limits to oxygen diffusion to the tissues during spiracle closure trigger ventilatory movements, which in turn support tissue demands. These findings contribute to our understanding of the mechanistic basis of respiratory gas exchange between insect tissues and the environment.
Sedentary behavior as a factor in determining lateral line contributions to rheotaxis
Authors: Bak-Coleman Joseph B. , Coombs Sheryl
Published: April 2014

Rheotaxis is a robust, multisensory behavior with many potential benefits for fish and other aquatic animals. Visual (optic flow) cues appear to be sufficient for rheotaxis, but other sensory cues can clearly compensate for the loss of vision. The role of various non-visual sensory systems, in particularly the flow-sensing lateral line, is poorly understood-largely due to widely varying methods and sensory conditions for studying rheotaxis. Here, we examine how sedentary behavior under visually deprived conditions affects the relative importance of lateral line cues in two species: one that is normally sedentary (the three-lined corydoras, Corydoras trilineatus) and one that normally swims continuously along the substrate (the blind cavefish, Astyanax mexicanus). No effect of lateral line disruption on rheotactic performance was found in blind cavefish, which were significantly more mobile than three-lined corydoras. By contrast, rheotaxis was significantly impaired at low, but not high, flow speeds in lateral-line deprived corydoras. In addition, lateral line enabled corydoras were characterized by decreased mobility and increased rheotactic performance relative to lateral line deprived fish. Taken together, these results suggest that sedentary behavior is an important factor in promoting reliance on lateral line cues.
Null point of discrimination in crustacean polarisation vision
Authors: How Martin J. , Christy John , Roberts Nicholas W. , Marshall N. Justin
Published: April 2014

The polarisation of light is used by many species of cephalopods and crustaceans to discriminate objects or to communicate. Most visual systems with this ability, such as that of the fiddler crab, include receptors with photopigments that are oriented horizontally and vertically relative to the outside world. Photoreceptors in such an orthogonal array are maximally sensitive to polarised light with the same fixed e-vector orientation. Using opponent neural connections, this two-channel system may produce a single value of polarisation contrast and, consequently, it may suffer from null points of discrimination. Stomatopod crustaceans use a different system for polarisation vision, comprising at least four types of polarisation-sensitive photoreceptor arranged at 0°, 45°, 90° and 135° relative to each other, in conjunction with extensive rotational eye movements. This anatomical arrangement should not suffer from equivalent null points of discrimination. To test whether these two systems were vulnerable to null points, we presented the fiddler crab Uca heteropleura and the stomatopod Haptosquilla trispinosa with polarised looming stimuli on a modified LCD monitor. The fiddler crab was less sensitive to differences in the degree of polarised light when the e-vector was at -45°, than when the e-vector was horizontal. In comparison, stomatopods showed no difference in sensitivity between the two stimulus types. The results suggest that fiddler crabs suffer from a null point of sensitivity, while stomatopods do not.
Fibrous Architectures of Porous Coordination Polymers–Alumina Composites Fabricated by Coordination Replication
Authors: Nakahama Masashi , Reboul Julien , Kamei Ken-ichiro , Kitagawa Susumu , Furukawa Shuhei
Published: April 2014

Polycrystalline fibers of porous coordination polymers (PCPs) were synthesized from free-standing alumina nanofiber materials by a coordination replication process. The diameter and morphology of fibrous PCP architectures were controlled by the concentration of aluminum salts and the pH of the reaction solution of replication, respectively. CO2 adsorption measurement proved the presence of hierarchical porosity composed of both micropores and mesopores in PCP fibers.
Role of the Clean Development Mechanism (Cdm) in the Development of National Energy Industries
Authors: Naik Mayuri R. , Singh Anju , Unnikrishnan Seema , Naik Neelima
Published: April 2014

Clean Development Mechanism (CDM) is an agreement under the Kyoto Protocol (1997) allowing industrialized (Annex-I) countries with Greenhouse Gas emission reduction commitment to invest in or finance projects that reduce emissions in developing countries using clean technologies. Under CDM, for every tonne of CO2 that does not enter into the atmosphere, a developing (Non-Annex-I) country earns one carbon credit which can be further sold to developed countries (Annex-I) through the international carbon market. Developed countries exchange these credits in terms of money and technology transfer with developing countries to meet their GHG emission reduction targets. 7391 CDM projects were registered worldwide by November 2013, out of which 6205 (84%) are under energy industry sector. India is contributing 828 (13%) CDM projects with estimated emission reduction of 69,156,926 metric tonnes of CO2e. By the end of the first commitment period (2012), 19,061,210 metric tonnes of CO2e emission reduction was achieved. The estimated range of annual CDM-generated revenue in India varies between US$10 and 330 million (Birla et.al.2012). India has the second largest number of CDM projects in the world. The National Clean Development Mechanism Authority (NCDMA) is the Designated National Authority (DNA) which was set up to evaluate and approve CDM projects. This paper provides a probing insight into these projects, and the methodologies used in order to achieve emission reduction by Indian industries.
Investigation of the mechanical properties of e-glass fabric reinforced SMC around hole on fiberglass reinforced composites materials
Authors: Karacaer Y. , Tarakçioğlu N. , Taşyürek M.
Published: April 2014

In this study, mechanical properties and fatigue damage behavior of E-Glass fiber - polyester perforated SMC and perforated SMC +Glass fabric were investigated. Middle of the samples 10 mm diameter hole was punched with laser beam. Tensile strength experiments performed in accordance with the ASTM D-3039. Fatigue experiments performed in accordance with the ASTM D-3479 standard. Fatigue test was done at R =0,05 stress ratio and 0,75 frequency.
Effect of different cooling methods on the corrosion behaviour at welded area of aluminium alloy
Authors: Wan Nik W. , Rosliza R. , Zulkifli M. , Hui D.
Published: April 2014

The effect of different cooling methods on the corrosion behaviour at welded area of aluminium alloy 5083 was investigated by using weight loss study, potendynamic polarization study and morphology study. All samples were cooled by using air cooling method and quenching method. There was an increase of weight loss for both cooling methods where samples with air cooling method showed lower percentage of weight loss as compared to samples with quenching methods. The corrosion rate gained from this study revealed that samples with air cooling method showed lower corrosion rate compared to samples with quenching method. In potentiodynamic polarization study, the value of corrosion current density, Icorr increased with respect to immersion period. This behaviour signifies the occurrence of porosity where the air cooled samples show lower value of Icorr compared to quenched samples. The increase in Icorr causes the value of polarization resistance, Rp to decrease and corrosion rate to increase. The morphology study conducted revealed the existence of porosity and caused pitting corrosion on quenched samples which proved the samples with quenching method was more corroded as compared to samples with air cooling method.
Multifunctional and specific interactions of CNTs in NBR and HNBR
Authors: Harishkumar Chougule , Giese Ulrich , Schuster Robert
Published: April 2014

There are different techniques in practice to disperse multiwalled carbon nanotubes (MWCNTs) in elastomers. In the present work, commercially available MWCNTs NANOCYL NC 7000™ are used as filler. A synthetic Nitrile Butadiene Rubber (NBR) and Hydrogenated Nitrile Butadiene Rubber (HNBR) were used as polymer matrix for the composites prepared by melt blending. The filler dispersion in HNBR was studied through Transmission Electron Microscopy (TEM). The mechanical properties are investigated through strain sweep and tensile tests. Dielectric measurements are carried out to study electrical conductivity of the nanocomposites. Dynamic mechanical measurements showed an enhanced Payne effect and improvement in stiffness with increase in CNTs content into rubber matrix An improvement in electrical and mechanical properties in both NBR and HNBR system resulted by an increase in filler loading. The mechanical and electric percolation threshold of CNTs was found at very low filler volume fraction. Equilibrium swelling experiments were used to study polymer-filler interaction with the help of Kraus plot and diffusion coefficient. NBR showed higher polymer-filler interaction compared to HNBR. In NBR nanocomposites, CNTs showed higher interaction than carbon black. Good dispersion and effective interaction of the CNTs with the polymer led to significant mechanical reinforcing effects.
Adsorption treatment of coal washery effluent (CWE) for the removal of suspended and dissolved particle (SDP) by chrysophylum albidium seed shell
Authors: Menkiti M. , Nwoye C. , Onukwuli O.
Published: April 2014

Chrysophylum albidium seed shell was utilized as an adsorbent for suspended and dissolved particle removal from coagulated coal washery effluent. Several parameters were investigated using batch mode and 23 full factorial central composite designs (CCD) (for optimization purposes). There exist single generality in optimal values for acid treated shell (ASAA) and salt treated shell (ASAS) at pH 6.8, 30°C, 10g/L dose, 30 min equilibrium time and 1g adsorbent mass for batch mode and CCD, respectively. Equilibrium data sufficiently fit the Langmuir isotherm (R2 > 0.99 and SSE (%) ≤ 0.093). Pseudo-second order kinetics provides best correlation (R2 > 0.99 and SSE (%) < 0.1) with experimental data. Thermodynamics constants (ΔG°, ΔH° and ΔS°) were respectively evaluated as -122.190 KJ/mol, 69005.967 J/mol and 228.146 Jmol-1K-1 for ASAA and -1537.455 KJ/mol, 68008.026 J/mol and 229.523 Jmol-1K-1 for ASAS. The shell biomass promises high potential as an efficient adsorbent since the adsorption process was favorable, endothermic and spontaneous.
Firm-Level Productivity, Risk, and Return
Authors: İmrohoroğlu Ayşe , Tüzel Şelale
Published: April 2014

This paper provides new evidence about the link between firm-level total factor productivity (TFP) and stock returns. We estimate firm-level TFP and show that it is strongly related to several firm characteristics such as size, the book-to-market ratio, investment, and hiring rate. Low productivity firms earn a significant premium over high productivity firms in the following year, and this premium is countercyclical. We show that a production-based asset pricing model calibrated to match the cross section of measured firm-level TFPs can replicate the empirical relationship between TFP, many firm characteristics, and stock returns. Our results offer an explanation as to how these firm characteristics rationally predict returns.

This paper was accepted by Wei Jiang, finance.
Real-Time Optimization of Personalized Assortments
Authors: Golrezaei Negin , Nazerzadeh Hamid , Rusmevichientong Paat
Published: April 2014

Motivated by the availability of real-time data on customer characteristics, we consider the problem of personalizing the assortment of products for each arriving customer. Using actual sales data from an online retailer, we demonstrate that personalization based on each customer's location can lead to over 10% improvements in revenue compared to a policy that treats all customers the same. We propose a family of index-based policies that effectively coordinate the real-time assortment decisions with the back-end supply chain constraints. We allow the demand process to be arbitrary and prove that our algorithms achieve an optimal competitive ratio. In addition, we show that our algorithms perform even better if the demand is known to be stationary. Our approach is also flexible and can be combined with existing methods in the literature, resulting in a hybrid algorithm that brings out the advantages of other methods while maintaining the worst-case performance guarantees.

This paper was accepted by Dimitris Bertsimas, special issue on business analytics.
Opportunistic Approachability and Generalized No-Regret Problems
Authors: Bernstein Andrey , Mannor Shie , Shimkin Nahum
Published: April 2014

Blackwell’s theory of approachability, introduced in 1956, has since proved a useful tool in the study of a range of repeated multiagent decision problems. Given a repeated matrix game with vector payoffs, a target set S is approachable by a certain player if he can ensure that the average payoff vector converges to that set, for any strategy of the opponent. In this paper we consider the case where a set need not be approachable in general, but may be approached if the opponent played favorably in some sense. In particular, we consider nonconvex sets that satisfy Blackwell’s dual condition, namely, can be approached when the opponent plays a stationary strategy. Whereas the convex hull of such a set is approachable, this is not generally the case for the original nonconvex set itself. We start by defining a sense of restricted play of the opponent (with stationary strategies being a special case), and then formulate appropriate goals for an opportunistic approachability algorithm that can take advantage of such restricted play as it unfolds during the game. We then consider a calibration-based approachability strategy that is opportunistic in that sense. A major motivation for this study comes from no-regret problems that lack a convex structure such as the problem of online learning with sample-path constraints, as formulated in Mannor et al. [Mannor S, Tsitsiklis JN, Yu JY (2009) Online learning with sample path constraints. J. Machine Learn. Res. 10:569–590]. Here the best-response-in-hindsight is not generally attainable, but only a convex relaxation thereof. Our proposed algorithm, while ensuring that relaxed goal, also comes closer to the nonrelaxed one when the opponent’s play is restricted in a well-defined sense.
Approximation Balancing Policies for Inventory Systems with Remanufacturing
Authors: Tao Zhijie , Zhou Sean X.
Published: April 2014

We consider a single-product, periodic-review inventory system with remanufacturable returned products, in which the serviceable product used to fulfill stochastic customer demand can be either manufactured from new parts or remanufactured from returned products. Demand and returns follow general stochastic processes and may be correlated, nonstationary, and evolving across different periods. The system costs include remanufacturing and manufacturing costs as well as inventory holding and demand backlogging costs. The objective is to minimize the expected total discounted cost over a finite planning horizon. The optimal policy for this model has a simple structure but its computation can be practically intractable because of the large and high-dimensional state space. Henceforth, we propose an efficient approximation algorithm based on cost balancing techniques to compute manufacturing and remanufacturing quantities in each period and show that the expected cost under this remanufacturing balancing policy is at most twice of the optimal one. Moreover, a numerical study demonstrates that the balancing policy generally performs much better than its worst-case bound. The analysis and results are also extended to cases with capacitated manufacturing and remanufacturing and multiple types of returned products.
Dangerous Close Call with Wintergreen Oil; Are 10 mL Syringes Needed When Giving Drugs via Venous Access Devices?; Use of “NoAC” Abbreviation; Unsafe Frequency Notation; 2014-15 Targeted Medication Safety Best Practices for Hospitals
Authors: Cohen Michael R. , Smetzer Judy L.
Published: April 2014

These medication errors have occurred in health care facilities at least once. They will happen again—perhaps where you work. Through education and alertness of personnel and procedural safeguards, they can be avoided. You should consider publishing accounts of errors in your news-letters and/or presenting them at your inservice training programs.

Your assistance is required to continue this feature. The reports described here were received through the Institute for Safe Medication Practices (ISMP) Medication Errors Reporting Program. Any reports published by ISMP will be anonymous. Comments are also invited; the writers’ names will be published if desired. ISMP may be contacted at the address shown below.

Errors, close calls, or hazardous conditions may be reported directly to ISMP through the ISMP Web site ( www.ismp.org ), by calling 800-FAIL-SAFE, or via e-mail at ismpinfo@ismp.org . ISMP guarantees the confidentiality and security of the information received and respects reporters’ wishes as to the level of detail included in publications.
Ciprofloxacin-Induced Syndrome of Inappropriate Antidiuretic Hormone; Anaphylactic Shock Due to Thrombolytic Administration; Hydroxychloroquine-Induced QT-Interval Prolongation; Complex Regional Pain Syndrome after Tetanus Toxoid Injection
Authors: Mancano Michael A.
Published: April 2014

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers.
Topiramate: Antipsychotic-Induced Weight Gain
Authors: Generali Joyce A. , Cada Dennis J.
Published: April 2014

This Hospital Pharmacy feature is extracted from Off-Label Drug Facts, a publication available from Wolters Kluwer Health. Off-Label Drug Facts is a practitioner-oriented resource for information about specific drug uses that are unapproved by the US Food and Drug Administration. This new guide to the literature enables the health care professional or clinician to quickly identify published studies on off-label uses and determine if a specific use is rational in a patient care scenario. References direct the reader to the full literature for more comprehensive information before patient care decisions are made. Direct questions or comments regarding Off-Label Drug Uses to jgeneral@ku.edu .
Leadership and Effective Succession Planning in Health-System Pharmacy Departments
Authors: Ellinger Lara Kathryn , Trapskin Philip J. , Black Raymond , Kotis Despina , Alexander Earnest
Published: April 2014

Leadership succession planning is crucial to the continuity of the comprehensive vision of the hospital pharmacy department. Leadership development is arguably the main component of training and preparing pharmacists to assume managerial positions. Succession planning begins with a review of the organizational chart in the context of the institution's strategic plan. Then career ladders are developed and key positions that require succession plans are identified. Employee profiles and talent inventory should be performed for all employees to identify education, talent, and experience, as well as areas that need improvement. Employees should set objective goals that align with the department's strategic plan, and management should work collaboratively with employees on how to achieve their goals within a certain timeframe. The succession planning process is dynamic and evolving, and periodic assessments should be conducted to determine how improvements can be made. Succession planning can serve as a marker for the success of hospital pharmacy departments.
Convergence Creates Opportunities across Health Care System
Authors: Fox Brent I. , Felkey Bill G.
Published: April 2014

Industrial design students at Auburn do a creativity exercise where they are asked to combine a common household appliance with an animal. Have you seen a snake light? In health technology, we have a similar opportunity. In the connection between jewelry and vital sign monitoring technology or household security and health status monitoring, we are witnessing active convergence that will benefit patients, providers, and health systems.
Ovarian Cycle Effects on Immediate Reward Selection Bias in Humans: A Role for Estradiol
Authors: Smith Christopher T. , Sierra Yecenia , Oppler Scott H. , Boettiger Charlotte A.
Published: April 2014

A variety of evidence suggests that, among humans, the individual tendency to choose immediate rewards (“Now”) over larger, delayed rewards (“Later”), or Now bias, varies with frontal dopamine (DA) levels. As cyclic elevations in estradiol (E+) modulate other frontal DA-dependent behaviors, we tested ovarian cycle effects on Now bias, and whether any such effects are E+ mediated. To do so, we quantified Now/Later choice behavior in naturally cycling adult females (n= 87; ages 18–40 years) during both the menstrual phase (MP; cycle day 1–2; low E+), and the follicular phase (FP; cycle day 11–12; high E+). Now bias decreased an average of 3.6% from MP to FP (p= 0.006). Measures of salivary E+ levels at each visit were available in a subsample of participants (n= 34). Participants with a verified E+ rise from MP to FP showed significantly greater decreases in Now bias at mid-cycle (n= 23) than those without a rise (n= 11;p= 0.03); Now bias decreased an average of 10.2% in the E+ rise group but increased an average of 7.9% in the no E+ rise group. The change in Now bias from MP to FP inversely correlated with the change in E+ (ρ = −0.39;p= 0.023), an effect driven by individuals with putatively lower frontal DA based on genotype at theVal158Metpolymorphism in theCOMTgene. This is the first demonstration that intertemporal choice varies across the ovarian cycle, with Now bias declining at mid-cycle, when fertility peaks. Moreover, our data suggest that the interacting effects of estradiol and frontal DA mediate this cycle effect on decision making.
Hidden Complexity of Synaptic Receptive Fields in Cat V1
Authors: Fournier Julien , Monier Cyril , Levy Manuel , Marre Olivier , Sári Katalin , Kisvárday Zoltán F. , Frégnac Yves
Published: April 2014

In the primary visual cortex (V1), Simple and Complex receptive fields (RFs) are usually characterized on the basis of the linearity of the cell spiking response to stimuli of opposite contrast. Whether or not this classification reflects a functional dichotomy in the synaptic inputs to Simple and Complex cells is still an open issue. Here we combined intracellular membrane potential recordings in cat V1 with 2D dense noise stimulation to decompose the Simple-like and Complex-like components of the subthreshold RF into a parallel set of functionally distinct subunits. Results show that both Simple and Complex RFs exhibit a remarkable diversity of excitatory and inhibitory Complex-like contributions, which differ in orientation and spatial frequency selectivity from the linear RF, even in layer 4 and layer 6 Simple cells. We further show that the diversity of Complex-like contributions recovered at the subthreshold level is expressed in the cell spiking output. These results demonstrate that the Simple or Complex nature of V1 RFs does not rely on the diversity of Complex-like components received by the cell from its synaptic afferents but on the imbalance between the weights of the Simple-like and Complex-like synaptic contributions.
Predictive Saccade Target Selection in Superior Colliculus during Visual Search
Authors: Shen Kelly , Paré Martin
Published: April 2014

Searching for a visual object naturally involves sequences of gaze fixations, during which the current foveal image is analyzed and the next object to inspect is selected as a saccade target. Fixation durations during such sequences are short, suggesting that saccades may be concurrently processed. Therefore, the selection of the next saccade target may occur before the current saccade target is acquired. To test this hypothesis, we trained four female rhesus monkeys (Macaca mulatta) to perform a multiple-fixation visual conjunction search task. We simultaneously recorded the activity of sensorimotor neurons in the midbrain superior colliculus (SC) in two monkeys. In this task, monkeys made multiple fixations before foveating the target. Fixation durations were significantly shorter than the latency of the initial responses to the search display, with approximately one-quarter being shorter than the shortest response latencies. The time at which SC sensorimotor activity discriminated the target from distracters occurred significantly earlier for the selection of subsequent fixations than for the selection of the first fixation. Target selection during subsequent fixations occurred even before the visual afferent delay in more than half of the neuronal sample, suggesting that the process of selection can encompass at least two future saccade targets. This predictive selection was present even when differences in saccade latencies were taken into account. Altogether, these findings demonstrate how neural representations on the visual salience map are processed in parallel, thus facilitating visual search.
Biphasic Mechanisms of Amphetamine Action at the Dopamine Terminal
Authors: Siciliano Cody A. , Calipari Erin S. , Ferris Mark J. , Jones Sara R.
Published: April 2014

In light of recent studies suggesting that amphetamine (AMPH) increases electrically evoked dopamine release ([DA]o), we examined discrepancies between these findings and literature that has demonstrated AMPH-induced decreases in [DA]o. The current study has expanded the inventory of AMPH actions by defining two separate mechanisms of AMPH effects on [DA]oat high and low doses, one dopamine transporter (DAT) independent and one DAT dependent, respectively. AMPH concentrations were measured via microdialysis in rat nucleus accumbens after intraperitoneal injections of 1 and 10 mg/kg and yielded values of ∼10 and 200 nm, respectively. Subsequently, voltammetry in brain slices was used to examine the effects of low (10 nm), moderate (100 nm), and high (10 μm) concentrations of AMPH across a range of frequency stimulations (one pulse; five pulses, 20 Hz; 24 pulses, 60 Hz). We discovered biphasic, concentration-dependent effects in WT mice, in which AMPH increased [DA]oat low concentrations and decreased [DA]oat high concentrations across all stimulation types. However, in slices from DAT-KO mice, [DA]owas decreased by all concentrations of AMPH, demonstrating that AMPH-induced increases in [DA]oare DAT dependent, whereas the decreases at high concentrations are DAT independent. We propose that low AMPH concentrations are insufficient to disrupt vesicular sequestration, and therefore AMPH acts solely as a DAT inhibitor to increase [DA]o. When AMPH concentrations are high, the added mechanism of vesicular depletion leads to reduced [DA]o. The biphasic mechanisms observed here confirm and extend the traditional actions of AMPH, but do not support mechanisms involving increased exocytotic release.
Long-Term Recordings Improve the Detection of Weak Excitatory–Excitatory Connections in Rat Prefrontal Cortex
Authors: Schwindel C. Daniela , Ali Karim , McNaughton Bruce L. , Tatsuno Masami
Published: April 2014

Characterization of synaptic connectivity is essential to understanding neural circuit dynamics. For extracellularly recorded spike trains, indirect evidence for connectivity can be inferred from short-latency peaks in the correlogram between two neurons. Despite their predominance in cortex, however, significant interactions between excitatory neurons (E) have been hard to detect because of their intrinsic weakness. By taking advantage of long duration recordings, up to 25 h, from rat prefrontal cortex, we found that 7.6% of the recorded pyramidal neurons are connected. This corresponds to ∼70% of the local E–E connection probability that has been reported by paired intracellular recordings (11.6%). This value is significantly higher than previous reports from extracellular recordings, but still a substantial underestimate. Our analysis showed that long recording times and strict significance thresholds are necessary to detect weak connections while avoiding false-positive results, but will likely still leave many excitatory connections undetected. In addition, we found that hyper-reciprocity of connections in prefrontal cortex that was shown previously by paired intracellular recordings was only present in short-distance, but not in long distance (∼300 micrometers or more) interactions. As hyper-reciprocity is restricted to local clusters, it might be a minicolumnar effect. Given the current surge of interest in very high-density neural spike recording (e.g., NIH BRAIN Project) it is of paramount importance that we have statistically reliable methods for estimating connectivity from cross-correlation analysis available. We provide an important step in this direction.
Synaptic Glutamate Spillover Due to Impaired Glutamate Uptake Mediates Heroin Relapse
Authors: Shen Hao-wei , Scofield Michael D. , Boger Heather , Hensley Megan , Kalivas Peter W.
Published: April 2014

Reducing the enduring vulnerability to relapse is a therapeutic goal in treating drug addiction. Studies with animal models of drug addiction show a marked increase in extrasynaptic glutamate in the core subcompartment of the nucleus accumbens (NAcore) during reinstated drug seeking. However, the synaptic mechanisms linking drug-induced changes in extrasynaptic glutamate to relapse are poorly understood. Here, we discovered impaired glutamate elimination in rats extinguished from heroin self-administration that leads to spillover of synaptically released glutamate into the nonsynaptic extracellular space in NAcore and investigated whether restoration of glutamate transport prevented reinstated heroin seeking. Through multiple functional assays of glutamate uptake and analyzing NMDA receptor-mediated currents, we show that heroin self-administration produced long-lasting downregulation of glutamate uptake and surface expression of the transporter GLT-1. This downregulation was associated with spillover of synaptic glutamate to extrasynaptic NMDA receptors within the NAcore. Ceftriaxone restored glutamate uptake and prevented synaptic glutamate spillover and cue-induced heroin seeking. Ceftriaxone-induced inhibition of reinstated heroin seeking was blocked by morpholino-antisense targeting GLT-1 synthesis. These data reveal that the synaptic glutamate spillover in the NAcore results from reduced glutamate transport and is a critical pathophysiological mechanism underling reinstated drug seeking in rats extinguished from heroin self-administration.