bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation of Neurokinin 3 Receptors in the Median Preoptic Nucleus Decreases Core Temperature in the Rat
Authors: Dacks Penny A. , Krajewski Sally J. , Rance Naomi E.
Published: October 2011

Estrogens have pronounced effects on thermoregulation, as illustrated by the occurrence of hot flushes secondary to estrogen withdrawal in menopausal women. Because neurokinin B (NKB) gene expression is markedly increased in the infundibular (arcuate) nucleus of postmenopausal women, and is modulated by estrogen withdrawal and replacement in multiple species, we have hypothesized that NKB neurons could play a role in the generation of flushes. There is no information, however, on whether the primary NKB receptor [neurokinin 3 receptor (NK3R)] modulates body temperature in any species. Here, we determine the effects of microinfusion of a selective NK3R agonist (senktide) into the rat median preoptic nucleus (MnPO), an important site in the heat-defense pathway. Senktide microinfusion into the rat MnPO decreased core temperature in a dose-dependent manner. The hypothermia induced by senktide was similar in ovariectomized rats with and without 17β-estradiol replacement. The hypothermic effect of senktide was prolonged in rats exposed to an ambient temperature of 29.0 C, compared with 21.5 C. Senktide microinfusion also altered tail skin vasomotion in rats exposed to an ambient temperature of 29.0 but not 21.5 C. Comparisons of the effects of senktide at different ambient temperatures indicated that the hypothermia was not secondary to thermoregulatory failure or a reduction in cold-induced thermogenesis. Other than a very mild increase in drinking, senktide microinfusion did not affect behavior. Terminal fluorescent dextran microinfusion showed targeting of the MnPO and adjacent septum, and immunohistochemical studies revealed that senktide induced a marked increase in Fos-activation in the MnPO. Because MnPO neurons expressed NK3R-immunoreactivity, the induction of MnPO Fos by senktide is likely a direct effect. By demonstrating that NK3R activation in the MnPO modulates body temperature, these studies support the hypothesis that hypothalamic NKB neurons could be involved in the generation of menopausal flushes.
Exploring the elephant: histopathology in high-throughput phenotyping of mutant mice
Authors: Schofield Paul N. , Vogel Peter , Gkoutos Georgios V. , Sundberg John P.
Published: October 2011

Recent advances in gene knockout techniques and the in vivo analysis of mutant mice, together with the advent of large-scale projects for systematic mouse mutagenesis and genome-wide phenotyping, have allowed the creation of platforms for the most complete and systematic analysis of gene function ever undertaken in a vertebrate. The development of high-throughput phenotyping pipelines for these and other large-scale projects allows investigators to search and integrate large amounts of directly comparable phenotype data from many mutants, on a genomic scale, to help develop and test new hypotheses about the origins of disease and the normal functions of genes in the organism. Histopathology has a venerable history in the understanding of the pathobiology of human and animal disease, and presents complementary advantages and challenges to in vivo phenotyping. In this review, we present evidence for the unique contribution that histopathology can make to a large-scale phenotyping effort, using examples from past and current programmes at Lexicon Pharmaceuticals and The Jackson Laboratory, and critically assess the role of histopathology analysis in high-throughput phenotyping pipelines.
Effects of ocean-acidification-induced morphological changes on larval swimming and feeding
Authors: Chan Kit Yu Karen , Grünbaum Daniel , O'Donnell Michael J.
Published: October 2011

Reduction in global ocean pH due to the uptake of increased atmospheric CO2 is expected to negatively affect calcifying organisms, including the planktonic larval stages of many marine invertebrates. Planktonic larvae play crucial roles in the benthic–pelagic life cycle of marine organisms by connecting and sustaining existing populations and colonizing new habitats. Calcified larvae are typically denser than seawater and rely on swimming to navigate vertically structured water columns. Larval sand dollars Dendraster excentricus have calcified skeletal rods supporting their bodies, and propel themselves with ciliated bands looped around projections called arms. Ciliated bands are also used in food capture, and filtration rate is correlated with band length. As a result, swimming and feeding performance are highly sensitive to morphological changes. When reared at an elevated PCO2 level (1000 ppm), larval sand dollars developed significantly narrower bodies at fourand six-arm stages. Morphological changes also varied between four observed maternal lineages, suggesting within-population variation in sensitivity to changes in PCO2 level. Despite these morphological changes, PCO2 concentration alone had no significant effect on swimming speeds. However, acidified larvae had significantly smaller larval stomachs and bodies, suggesting reduced feeding performance. Adjustments to larval morphologies in response to ocean acidification may prioritize swimming over feeding, implying that negative consequences of ocean acidification are carried over to later developmental stages.
Static inflation and deflation pressure–volume curves from excised lungs of marine mammals
Authors: Fahlman Andreas , Loring Stephen H. , Ferrigno Massimo , Moore Colby , Early Greg , Niemeyer Misty , Lentell Betty , Wenzel Frederic , Joy Ruth , Moore Michael J.
Published: October 2011

Excised lungs from eight marine mammal species [harp seal (Pagophilus groenlandicus), harbor seal (Phoca vitulina), gray seal (Halichoerus grypush), Atlantic white-sided dolphin (Lagenorhynchus acutus), common dolphin (Delphinus delphis), Risso's dolphin (Grampus griseus), long-finned pilot whale (Globicephala melas) and harbor porpoise (Phocoena phocoena)] were used to determine the minimum air volume of the relaxed lung (MAV, N=15), the elastic properties (pressure–volume curves, N=24) of the respiratory system and the total lung capacity (TLC). Our data indicate that mass-specific TLC (sTLC, l kg–1) does not differ between species or groups (odontocete vs phocid) and agree with that estimated (TLCest) from body mass (Mb) by applying the equation: TLCest=0.135 Mb0.92. Measured MAV was on average 7% of TLC, with a range from 0 to 16%. The pressure–volume curves were similar among species on inflation but diverged during deflation in phocids in comparison with odontocetes. These differences provide a structural basis for observed species differences in the depth at which lungs collapse and gas exchange ceases.
Non-invasive study ofOctopus vulgarisarm morphology using ultrasound
Authors: Margheri Laura , Ponte Giovanna , Mazzolai Barbara , Laschi Cecilia , Fiorito Graziano
Published: October 2011

Octopus arms are extremely dexterous structures. The special arrangements of the muscle fibers and nerve cord allow a rich variety of complex and fine movements under neural control. Historically, the arm structure has been investigated using traditional comparative morphological ex vivo analysis. Here, we employed ultrasound imaging, for the first time, to explore in vivo the arms of the cephalopod mollusc Octopus vulgaris. Sonographic examination (linear transducer, 18 MHz) was carried out in anesthetized animals along the three anatomical planes: transverse, sagittal and horizontal. Images of the arm were comparable to the corresponding histological sections. We were able, in a non-invasive way, to measure the dimensions of the arm and its internal structures such as muscle bundles and neural components. In addition, we evaluated echo intensity signals as an expression of the difference in the muscular organization of the tissues examined (i.e. transverse versus longitudinal muscles), finding different reflectivity based on different arrangements of fibers and their intimate relationship with other tissues. In contrast to classical preparative procedures, ultrasound imaging can provide rapid, destruction-free access to morphological data from numerous specimens, thus extending the range of techniques available for comparative studies of invertebrate morphology.
Carbon isotopic fractionation in eider adipose tissue varies with fatty acid structure: implications for trophic studies
Authors: Budge Suzanne M. , Wang Shiway W. , Hollmén Tuula E. , Wooller Matthew J.
Published: October 2011

Carbon isotopic fractionation was investigated in fatty acids (FA) of adipose tissue and blood serum of threatened Steller's eiders (Polysticta stelleri) and spectacled eiders (Somateria fischeri) relative to the FA in their diets. Captive eiders were fed a known diet for 180 days with serum sampled at 60, 120 and 180 days immediately after a 12 fast; adipose was collected at 180 days. Essential FA (EFA) in the adipose showed varying degrees of isotope fractionation (0–4‰), depending on FA structure. The δ13C values of long-chain FA 20:5n-3 and 22:6n-3 did not differ from those in the diet, while those of 18:2n-6 and 18:3n-3 were ∼2‰ greater than in the diet. The δ13C values of free FA (FFA) in serum were not consistent within individuals or sampling dates; fractionation varied randomly, suggesting that FFA were arising from diet, rather than mobilization from adipose tissue. Discrimination factors were used in combination with a mixing model incorporating FA and lipid concentrations to estimate the diet of eiders fed a binary mixture with contrasting isotopic signatures. Diet estimates varied with FA but mean values closely approximated the actual proportions consumed. By tracking EFA, this study avoided the complications in interpretation arising from isotopic routing of carbon in bulk isotope analyses and serves as a basis for the development of compound-specific isotopic methods to trace dietary input in wild eiders. However, our understanding of the processes contributing to the variation in isotopic signatures of FA in nature is currently limited, and we recommend that future research directions focus on elucidating these mechanisms.
Penguin head movement detected using small accelerometers: a proxy of prey encounter rate
Authors: Kokubun Nobuo , Kim Jeong-Hoon , Shin Hyoung-Chul , Naito Yasuhiko , Takahashi Akinori
Published: October 2011

Determining temporal and spatial variation in feeding rates is essential for understanding the relationship between habitat features and the foraging behavior of top predators. In this study we examined the utility of head movement as a proxy of prey encounter rates in medium-sized Antarctic penguins, under the presumption that the birds should move their heads actively when they encounter and peck prey. A field study of free-ranging chinstrap and gentoo penguins was conducted at King George Island, Antarctica. Head movement was recorded using small accelerometers attached to the head, with simultaneous monitoring for prey encounter or body angle. The main prey was Antarctic krill (>99% in wet mass) for both species. Penguin head movement coincided with a slow change in body angle during dives. Active head movements were extracted using a high-pass filter (5 Hz acceleration signals) and the remaining acceleration peaks (higher than a threshold acceleration of 1.0 g) were counted. The timing of head movements coincided well with images of prey taken from the back-mounted cameras: head movement was recorded within ±2.5 s of a prey image on 89.1±16.1% (N=7 trips) of images. The number of head movements varied largely among dive bouts, suggesting large temporal variations in prey encounter rates. Our results show that head movement is an effective proxy of prey encounter, and we suggest that the method will be widely applicable for a variety of predators.
Developmentally regulated multisensory integration for prey localization in the medicinal leech
Authors: Harley Cynthia M. , Cienfuegos Javier , Wagenaar Daniel A.
Published: October 2011

Medicinal leeches, like many aquatic animals, use water disturbances to localize their prey, so they need to be able to determine if a wave disturbance is created by prey or by another source. Many aquatic predators perform this separation by responding only to those wave frequencies representing their prey. As leeches' prey preference changes over the course of their development, we examined their responses at three different life stages. We found that juveniles more readily localize wave sources of lower frequencies (2 Hz) than their adult counterparts (8–12 Hz), and that adolescents exhibited elements of both juvenile and adult behavior, readily localizing sources of both frequencies. Leeches are known to be able to localize the source of waves through the use of either mechanical or visual information. We separately characterized their ability to localize various frequencies of stimuli using unimodal cues. Within a single modality, the frequency–response curves of adults and juveniles were virtually indistinguishable. However, the differences between the responses for each modality (visual and mechanosensory) were striking. The optimal visual stimulus had a much lower frequency (2 Hz) than the optimal mechanical stimulus (12 Hz). These frequencies matched, respectively, the juvenile and the adult preferred frequency for multimodally sensed waves. This suggests that, in the multimodal condition, adult behavior is driven more by mechanosensory information and juvenile behavior more by visual. Indeed, when stimuli of the two modalities were placed in conflict with one another, adult leeches, unlike juveniles, were attracted to the mechanical stimulus much more strongly than to the visual stimulus.
Ultrasound biomicroscopy for biomechanical characterization of healthy and injured triceps surae of rats
Authors: Peixinho C. C. , Ribeiro M. B. , Resende C. M. C. , Werneck-de-Castro J. P. S. , de Oliveira L. F. , Machado J. C.
Published: October 2011

This work describes the use of ultrasound biomicroscopy (UBM) to follow up the degeneration–regeneration process after a laceration injury induced in the lateral gastrocnemius (LG) and soleus (SOL) muscles of rats. UBM (40 MHz) images were acquired and used for biomechanical characterization of muscular tissue, specifically using pennation angle (PA) and muscle thickness (MT). The animals were distributed in three groups: the variability group (VG; N=5), the gastrocnemius injured group (GG; N=6) and the soleus injured group (SG; N=5). VG rats were used to assess data variability and reliability (coefficients of variation of 9.37 and 3.97% for PA and MT, respectively). GG and SG rats were submitted to the injury protocol in the LG and SOL muscles of the right legs, respectively. UBM images of muscles of both legs were acquired at the following time points: before and after injury (immediately, 7, 14, 21 and 28 days). We observed an increase in PA for the non-injured leg 28 days after injury for both GG and SG rats (GG=10.68 to 16.53 deg and SG=9.65 to 14.06 deg; P<0.05). Additionally, MT presented a tendency to increase (GG=2.92 to 3.13 mm and SG=2.12 to 2.35 mm). Injured legs maintained pre-injury PA and MT values. It is suggested that a compensatory hypertrophic response due to the overload condition imposed to healthy leg. The results indicate that UBM allows qualitative and quantitative muscle differentiation among healthy and injured muscle at different stages after lesion.
An aphid's Odyssey – the cortical quest for the vascular bundle
Authors: Hewer Angela , Becker Alexander , van Bel Aart J. E.
Published: October 2011

Sensing pH and sucrose concentration (with a preference for pH values of 7.0–7.5 and sucrose concentrations of approximately 400 mmol l–1) enables aphids to recognise sieve tubes inside vascular bundles. However, it is still unclear how aphids find their way to the vascular bundles. Membrane potentials in the cortex of Vicia faba stems were measured along a radial transect from the epidermis to the sieve elements and there was no gradient detected that could be used by aphids to guide their stylets to the sieve elements. Additionally, aphids did not demonstrate a preference between artificial diets with low or high levels of dissolved oxygen, making it unlikely that oxygen gradients in the cortex assist orientation towards the phloem. Tracks of salivary sheaths indicate that aphids search for vascular bundles in a radial direction (perpendicular from the stem surface to the vascular bundle) with regular side punctures in a pre-programmed fashion. Optical examination and electrical penetration graph (EPG) recordings suggest that aphids (Megoura viciae) probe the vacuolar sap of cortex cells. Acidic pH (5.0–5.5) and low sucrose concentrations in vacuoles, therefore, may provoke aphids to retract their stylets and probe the next cell until a favourable cell sap composition is encountered. The importance of sucrose as a cue was demonstrated by the experimental manipulation of Ricinus communis plants that cause them to transport hexoses instead of sucrose. Aphids (Aphis fabae) ingested less phloem sap of plants transporting hexoses compared with plants transporting the normal sucrose. The proposed rejection–acceptance behaviour provides a universal plant-directed mode of how aphids orientate their stylets towards the phloem.
Ecologically relevant measures of tolerance to potentially lethal temperatures
Authors: Terblanche John S. , Hoffmann Ary A. , Mitchell Katherine A. , Rako Lea , le Roux Peter C. , Chown Steven L.
Published: October 2011

The acute thermal tolerance of ectotherms has been measured in a variety of ways; these include assays where organisms are shifted abruptly to stressful temperatures and assays where organisms experience temperatures that are ramped more slowly to stressful levels. Ramping assays are thought to be more relevant to natural conditions where sudden abrupt shifts are unlikely to occur often, but it has been argued that thermal limits established under ramping conditions are underestimates of true thermal limits because stresses due to starvation and/or desiccation can arise under ramping. These confounding effects might also impact the variance and heritability of thermal tolerance. We argue here that ramping assays are useful in capturing aspects of ecological relevance even though there is potential for confounding effects of other stresses that can also influence thermal limits in nature. Moreover, we show that the levels of desiccation and starvation experienced by ectotherms in ramping assays will often be minor unless the assays involve small animals and last for many hours. Empirical data illustrate that the combined effects of food and humidity on thermal limits under ramping and sudden shifts to stressful conditions are unpredictable; in Drosophila melanogaster the presence of food decreased rather than increased thermal limits, whereas in Ceratitis capitata they had little impact. The literature provides examples where thermal limits are increased under ramping presumably because of the potential for physiological changes leading to acclimation. It is unclear whether heritabilities and population differentiation will necessarily be lower under ramping because of confounding effects. Although it is important to clearly define experimental methods, particularly when undertaking comparative assessments, and to understand potential confounding effects, thermotolerance assays based on ramping remain an important tool for understanding and predicting species responses to environmental change. An important area for further development is to identify the impact of rates of temperature change under field and laboratory conditions.
CRF treatment induces a readjustment in glucosensing capacity in the hypothalamus and hindbrain of rainbow trout
Authors: Conde-Sieira Marta , Librán-Pérez Marta , López Patiño Marcos A. , Míguez Jesús M. , Soengas José L.
Published: October 2011

Stress conditions induced in rainbow trout a readjustment in the glucosensing response of the hypothalamus and hindbrain such that those sensors did not respond properly to changes in glucose levels, as demonstrated in previous studies. To evaluate the hypothesis that corticotropin-releasing factor (CRF) could be involved in that response, we have incubated the hypothalamus and hindbrain of rainbow trout at different glucose concentrations in the presence of different concentrations of CRF. Under those conditions, we evaluated whether parameters related to glucosensing [the levels of glucose, glycogen and glucose 6-phosphate, the activities of glucokinase (GK), glycogen synthase (GSase) and pyruvate kinase (PK), and mRNA abundance of transcripts for GK, Glut2, Kir.6-like and sulfonylurea receptor (SUR)-like] are modified in the presence of CRF in a way comparable to that observed under stress conditions. We obtained evidence allowing us to suggest that CRF could be involved in the interaction between stress and glucosensing as CRF treatment of the hypothalamus and hindbrain in vitro induced a readjustment in glucosensing parameters similar to that previously observed under stress conditions in vivo. We had also previously demonstrated that stress elicits alterations in food intake in parallel with the readjustment of glucosensing systems. Here, we provide evidence that the mRNA abundance of several of the neuropeptides involved in the regulation of food intake, such as neuropeptide Y (NPY) or cocaineand amphetamine-regulated transcript (CART), is affected by CRF treatment, in such a way that their expression does not respond to changes in glucose levels in the same way as controls, allowing us to suggest that the food intake response that is integrated by changes in those peptides and known to be reduced by stress could be also mediated by CRF action in glucosensing areas.
Recent Progress in Chemical Characterization of Supported Gold Catalysts: CO Adsorption on Au/Ceria–Zirconia
Authors: Delgado Juan J , Cíes José M , López-Haro Miguel , del Río Eloy , Calvino José J , Bernal Serafín
Published: October 2011

An approach correlating quantitative CO adsorption data with the nanostructural properties of Au/CeO2–ZrO2 catalysts is discussed. It has been used to show that the CO adsorption occurs on Au sites with coordination number ≤7, that Au dispersion has a dramatic influence on the amount of CO strongly chemisorbed on the support, and that a fully reversible SMSI effect may be induced by successive mild reduction and reoxidation treatments.
197Au Mössbauer Spectroscopy of Au25(SG)18− Revisited
Authors: Tsukuda Tatsuya , Negishi Yuichi , Kobayashi Yasuhiro , Kojima Norimichi
Published: October 2011

Reanalysis of the 197Au Mössbauer spectrum of Au25(SG)18− (SG: glutathionate) based on the structure determined by single-crystal XRD analysis gave a reasonable fit, demonstrating that 197Au Mössbauer spectroscopy is a powerful tool for predicting the structural motifs of thiolate-protected Au clusters.
Size Regulation of Si Nanoparticles through Photon-enhanced Chemical Etching
Authors: Azuma Shogo , Sato Seiichi
Published: October 2011

A Si nanoparticle surface was etched in an aqueous HF solution under monochromatic light irradiation in the infrared-to-visible region. The average size of the nanoparticles was controlled by changing the photon energy of the irradiating light. After prolonged photoetching, the size distribution of the nanoparticles was narrowed significantly. The correlation between the photon energy and the final size of the nanoparticles indicated that the band gap energy change due to the quantum size effect played an important role in controlling nanoparticle size.
Novel Method for Surface Modification of Silicone-containing Hydrogel Using Addition Reaction
Authors: Yokota Mitsuru , Shimoyama Naoki , Fujisawa Kazuhiko , Nakamura Masataka , Ajiro Hiroharu , Akashi Mitsuru
Published: October 2011

We designed a novel surface modification method of shaped articles from silicone-containing hydrogel using hydrosilylation reaction between silicone component and poly(ethylene glycol) (PEG) chain in order to improve the surface wettability. For the introduction of –SiH group to hydrogel, in addition to copolymerization of –SiH-containing methacrylate, argon gas plasma treatment was found to be effective. Hydrosilylation reaction between shaped article and PEG easily proceeded in organic solvent, and the resultant hydrogel showed reduced contact angle after the hydration in water. FTIR-ATR measurement suggested the validity of our process design concept.
Atomic Oxygen-resistant Phosphorus-containing Polyimides Derived from Bis(4-aminophenoxy)phenylphosphine Oxide and Aromatic Dianhydrides
Authors: Xiao Fei , Wang Kai , Zhan Maosheng
Published: October 2011

A series of phosphorus-containing polyimides are prepared from p-DAPO3 and corresponding dianhydrides by two-stage polycondensation, and properties such as AO resistance are discussed in detail.
Unusually Long trans/gauche Conformational Equilibration Time during the Melting Process of BmimCl, a Prototype Ionic Liquid
Authors: Okajima Hajime , Hamaguchi Hiro-o
Published: October 2011

The melting process of 1-butyl-3-methylimidazolium chloride (bmimCl), a prototype room-temperature ionic liquid, has been studied with fast low frequency Raman spectroscopy. Simultaneous tracing of the lattice vibrations and trans/gauche conformational marker bands reveals that the conformational change in the butyl group occurs a few seconds after the loss of lattice vibrations. This finding indicates that the alkyl chain interaction in bmimCl is so strong that the butyl conformation hardly changes in the very early stage of melting.
Flow cytometry in clinical pathology
Authors: Virgo Paul F , Gibbs Graham J
Published: October 2011

Flow cytometry has had an impact upon all areas of clinical pathology and now, in the 21st century, it is truly coming of age. This study reviews the application of flow cytometry within clinical pathology with an emphasis upon haematology and immunology. The basic principles of flow cytometry are discussed, including the principles and considerations of the flow-cell and hydrodynamic focusing, detector layout and function, use of fluorochromes and multicolour flow cytometry (spectral overlap and colour compensation), alongside the strategies available for sample preparation, data acquisition and analysis, reporting of results, internal quality control, external quality assessment and flow sorting. The practice of flow cytometry is discussed, including the principles and pitfalls associated with leukocyte immunophenotyping for leukaemia and lymphoma diagnosis, immune deficiency, predicting and monitoring response to monoclonal antibody therapy, rare event detection and screening for genetic disease. Each section is illustrated with a case study. Future directions are also discussed.
Structure and stability of RNA/RNA kissing complex: with application to HIV dimerization initiation signal
Authors: Cao Song , Chen Shi-Jie
Published: October 2011

We develop a statistical mechanical model to predict the structure and folding stability of the RNA/RNA kissing-loop complex. One of the key ingredients of the theory is the conformational entropy for the RNA/RNA kissing complex. We employ the recently developed virtual bond-based RNA folding model (Vfold model) to evaluate the entropy parameters for the different types of kissing loops. A benchmark test against experiments suggests that the entropy calculation is reliable. As an application of the model, we apply the model to investigate the structure and folding thermodynamics for the kissing complex of the HIV-1 dimerization initiation signal. With the physics-based energetic parameters, we compute the free energy landscape for the HIV-1 dimer. From the energy landscape, we identify two minimal free energy structures, which correspond to the kissing-loop dimer and the extended-duplex dimer, respectively. The results support the two-step dimerization process for the HIV-1 replication cycle. Furthermore, based on the Vfold model and energy minimization, the theory can predict the native structure as well as the local minima in the free energy landscape. The root-mean-square deviations (RMSDs) for the predicted kissing-loop dimer and extended-duplex dimer are ∼3.0 Å. The method developed here provides a new method to study the RNA/RNA kissing complex.
Autoregulation of the nonsense-mediated mRNA decay pathway in human cells
Authors: Yepiskoposyan Hasmik , Aeschimann Florian , Nilsson Daniel , Okoniewski Michal , Mühlemann Oliver
Published: October 2011

Nonsense-mediated mRNA decay (NMD) is traditionally portrayed as a quality-control mechanism that degrades mRNAs with truncated open reading frames (ORFs). However, it is meanwhile clear that NMD also contributes to the post-transcriptional gene regulation of numerous physiological mRNAs. To identify endogenous NMD substrate mRNAs and analyze the features that render them sensitive to NMD, we performed transcriptome profiling of human cells depleted of the NMD factors UPF1, SMG6, or SMG7. It revealed that mRNAs up-regulated by NMD abrogation had a greater median 3′-UTR length compared with that of the human mRNAome and were also enriched for 3′-UTR introns and uORFs. Intriguingly, most mRNAs coding for NMD factors were among the NMD-sensitive transcripts, implying that the NMD process is autoregulated. These mRNAs all possess long 3′ UTRs, and some of them harbor uORFs. Using reporter gene assays, we demonstrated that the long 3′ UTRs of UPF1, SMG5, and SMG7 mRNAs are the main NMD-inducing features of these mRNAs, suggesting that long 3′ UTRs might be a frequent trigger of NMD.
A Short-Range Scheduling Model for Blockbuster's Order-Processing Operation
Authors: Chung Casey , Dawande Milind , Rajamani Divakar , Sriskandarajah Chelliah
Published: October 2011

Blockbuster Inc., a chain of VHS, DVD, Blu-ray, and video game rental stores, has developed a highly specialized distribution network. The company maintains a single distribution center in which it receives products from suppliers, and processes and packs them for shipping to stores across the United States. The volumes of particular products and the number of different products shipped in a week have significant week-to-week volatility. Short lead times are typical because of supplier manufacturing delays and strict in-store due-date requirements. At the distribution center, processing and packing are scheduled through multiple processing departments that compete for use of shared merge conveyors and shared sortation systems. Blockbuster's general processing and packing goal is on-time delivery of products to stores while controlling costs.

In this paper, we describe the development and implementation of a mixed-integer programming model to schedule Blockbuster's short-range order-processing operations. Implemented beginning in January 2007, the model has helped Blockbuster to maintain timely shipping, reduce related labor and transportation costs, improve capacity utilization, and attain a better understanding of how to achieve further improvements. Blockbuster's structure, in which multiple processing departments compete for subsequent shared resources, such as merge conveyors and sortation systems, is common in other industries; therefore, we also discuss the relevance of this model to other organizations.
Introduction: 2010 Daniel H. Wagner Prize for Excellence in Operations Research Practice
Authors: Butler C. Allen , Robinson Randall S.
Published: October 2011

Competition for the 2010 Daniel H. Wagner Prize for Excellence in Operations Research Practice provided the five finalist papers featured in this special issue of Interfaces. The prestigious Wagner Prize emphasizes quality and originality of mathematical models along with clarity of written and oral exposition. Authors from IBM's Watson Research Center won the competition with their innovative, diverse suite of models to improve critical choices for managing skilled personnel, choices so important in service industries; their models have been implemented in the IBM Integrated Technology Services business. A finalist team from Georgia Tech joined with the US Centers for Disease Control to solve a physician's often challenging problem of creating the best new schedule for a person who misses one or more previously scheduled vaccinations; the team's optimization approach is implemented in software now freely available to American physicians, and in software with Canadian rules soon to be available to Canadian physicians. A team from Kimberly-Clark Latin America and Penn State University developed optimization models to improve production and inventory control; after overcoming slow solution speeds with heuristics that furnish good solutions in minutes, the models have so far been implemented in Kimberly-Clark plants in five countries. A finalist team from the University of Texas at Dallas worked with Blockbuster, Inc. to improve efficiency and speed in Blockbuster's central system to fill orders from the company's numerous retail stores; implementation of the resulting optimization models led to reduced costs and more balanced workloads in the Blockbuster order-fulfillment center where different processing departments compete for shared resources. Finally, an India-based team from GE Global Research developed models to improve the selection of customers who receive special product offers from a GE commercial bank in Europe; the team's diverse models are now helping the GE bank to improve its customer responses.
OnTheMark: Integrated Stochastic Resource Planning of Human Capital Supply Chains
Authors: Cao Heng , Hu Jianying , Jiang Chen , Kumar Tarun , Li Ta-Hsin , Liu Yang , Lu Yingdong , Mahatma Shilpa , Mojsilović Aleksandra , Sharma Mayank , Squillante Mark S. , Yu Yichong
Published: October 2011

In this paper, we present a suite of innovative operations research models and methods called OnTheMark (OTM). This suite supports the effective management of human capital supply chains by addressing distinct features of human talent that cannot be handled via traditional supply chain management. OTM consists of novel solutions for (1) statistical forecasting of demand and human capital requirements, (2) risk-based stochastic human-talent capacity planning, (3) stochastic modeling and optimization (control) of human capital supply evolutionary dynamics over time, (4) optimal multiskill supply-demand matching, and (5) stochastic optimization of business decisions and investments to manage human capital shortages and overages. The OTM suite was developed and deployed as an important part of the human capital management and planning process within IBM, providing support for decision making to drive better business performance. This is achieved through important contributions in the areas of stochastic models and optimization (control), and the innovative application and integration of these models and methods in human capital management applications.
Multicentric Osteosarcoma
Authors: Corradi Domenico , Wenger Doris E. , Bertoni Franco , Bacchini Patrizia , Bosio Silvia , Goldoni Matteo , Unni K. Krishnan , Sim Franklin H. , Inwards Carrie Y.
Published: October 2011

Multicentric osteosarcoma (M-OGS) is characterized by multicentricity of osseous osteosarcomas, either synchronous or metachronous, without visceral involvement. The study’s purpose was to clinicopathologically and radiographically analyze 56 cases of M-OGS (22 synchronous and 34 metachronous). The distal femur was the most common site. Histologically, all tumors were high grade. Of 22 patients with synchronous M-OGS, 16 had 3 or more simultaneous tumors; the axial skeleton was involved in 14 (64%) of 22 cases. In metachronous M-OGS, the second malignancy occurred after a median of 22 months. Treatment was surgery, chemotherapy, radiotherapy, or a combination of these. Patients with metachronous osteosarcoma had a median survival longer than did patients with synchronous tumors. Overall, 8 long-term survivors were treated by aggressive surgery with wide margins (plus chemotherapy and/or radiotherapy). M-OGS combines multiple skeletal locations of high-grade conventional osteosarcomas and has a poor prognosis. Aggressive surgery may result in improved long-term survival, particularly in patients with metachronous disease.
Pharmacist-Led Group Medical Appointments for the Management of Type 2 Diabetes with Comorbid Depression in Older Adults
Authors: Taveira Tracey H , Dooley Andrea G , Cohen Lisa B , Khatana Sameed Ahmed M , Wu Wen-Chih
Published: October 2011

Background::

Depression is associated with poor glycemic control, increased number of microvascular and macrovascular complications, functional impairment, mortality, and 4.5 times higher total health care costs in patients with diabetes. Shared medical appointments (SMAs) may be an effective method to attain national guideline recommendations for glycemic control in diabetes for patients with depression through peer support, counseling, problem solving, and improved access to care.

Objective:

To test the efficacy as assessed by attainment of a hemoglobin A1c (A1C) <7% of pharmacistted group SMA visits, Veterans Affairs Multidisciplinary Education in Diabetes and Intervention for Cardiac Risk Reduction in Depression (VA-MEDIC-D), in patients with type 2 diabetes mellitus.

Methods:

This was a randomized controlled trial of VA-MEDIC-D added to standard care versus standard care alone in depressed patients with diabetes with A1C >6.5%. VA-MEDIC-D consisted of 4 once-weekly, 2-hour sessions followed by 5 monthly 90-minute group sessions. Each SMA session consisted of multidisciplinary education and pharmacist-led behavioral and pharmacologic interventions for diabetes, lipids, smoking, and blood pressure. No pharmacologic interventions for depression were provided. The change in the proportion of participants who achieved an A1C <7% at 6 months was compared.

Results:

Compared to standard care (n = 44), a lower proportion of patients in VA-MEDIC-D (n = 44) had systolic blood pressure (SBP) <130 mm Hg at baseline, but were similar in other cardiovascular risk factors and psychiatric comorbidity. The change in the proportion of participants achieving an A1C <7% was greater in the VA-MEDIC-D arm than in the standard care arm (29.6% vs 11.9%), with odds ratio 3.6 (95% CI 1.1 to 12.3). VA-MEDIC-D participants also achieved significant reductions in SBP, low-density lipoprotein cholesterol, and non–high-density lipoprotein (HDL) cholesterol from baseline, whereas significant reductions were attained only in non–HDL cholesterol with standard care. There was no significant change in depressive symptoms for either arm.

Conclusions:

Pharmacist-led group SMA visits are efficacious in attainment of glycemic control in patients with diabetes and depression without change in depression symptoms.
Rosiglitazone and Pioglitazone for the Treatment of Alzheimer's Disease
Authors: Miller Benjamin W , Willett Kristine C , Desilets Alicia R
Published: October 2011

Objective:

To review the literature on the efficacy and safety of rosiglitazone and pioglitazone for the treatment of Alzheimer's disease (AD).

Data Sources:

Literature was accessed through MEDLINE (1948-August 2011 week 2) and EMBASE (1980-2011 week 32) using the search terms rosiglitazone, pioglitazone, and Alzheimer's disease. Results were limited to studies conducted in humans and published in English.

Study Selection And Data Ektraction:

Clinical trials evaluating the efficacy and safety of rosiglitazone or pioglitazone in patients with AD were critically evaluated.

Data Synthesis:

The mechanism for development of AD has been linked to both inflammation and decreased insulin sensitivity. Because of this, rosiglitazone and pioglitazone have been evaluated as potential treatments for AD because of their insulin-sensitizing and antiinflammatory effects. Five clinical trials were evaluated (3 assessing rosiglitazone, 2 assessing pioglitazone); 1 trial evaluating rosiglitazone demonstrated a beneficial effect on cognition in patients with probable AD. However, the largest randomized, double-blind, placebo-controlled trials conducted to date failed to demonstrate a difference between rosiglitazone and placebo when assessing primary endpoints. Two small trials evaluating pioglitazone produced conflicting results regarding efficacy in AD; numerous limitations make results difficult to interpret. The safety of these agents was also evaluated in these trials; edema was seen more commonly in patients receiving rosiglitazone or pioglitazone than in those receiving placebo; however, each drug was generally well tolerated.

Conclusions:

Resufts from clinical trials and current safety data suggest that rosiglitazone should not be used for the treatment of AD. Application of results from trials evaluating pioglitazone in the treatment of AD is limited because of major trial limitations; therefore, it should not be recommended at this time. Although these drugs are not commonly used in the treatment of AD, further pharmacoepidemiologic studies are warranted before their use can be recommended.
The Use of Activated Recombinant Factor VII in a Patient with Fulminant Hepatic Failure Requiring Placement of an Intracranial Pressure Monitor
Authors: Meadows Holly B , Krisl Jill C , Greenberg Charles S , Mazur Joseph E
Published: October 2011

Objective:

To evaluate the use of recombinant activated factor VII (rFVIIa) in a patient with fulminant hepatic failure (FHF) requiring placement of an intracranial pressure monitor.

Case Summary:

A 21-year-old female with no significant medical history was admitted to an outside hospital with elevated results of liver function tests. Subsequently, the patient was diagnosed with autoimmune hepatitis. Systemic corticosteroids were started, but her condition continued to decompensate. She was transferred to our tertiary care facility 5 days after initial presentation. The liver function test results remained elevated (eg, total bilirubin 27 mg/dL), and international normalized ratio (INR) was 3.57. The medical team decided to place an intracranial pressure monitor, with the neurosurgery team's goal being an INR less than 1.5 before placement of the monitor. After multiple units of fresh frozen plasma (FFP) failed to lower the patient's INR, rFVIIa 40 μg/kg was administered. A rapid decrease of the INR allowed the neurosurgery team to perform the procedure without complications.

Discussion:

The use of rFVIIa allowed for decrease of this patient's INR after multiple units of FFP had failed to correct it. The utility of INR as a marker of coagulopathy in fulminant hepatic failure has been debated, but it is currently used as the standard laboratory test prior to invasive procedures, as in the case presented here.

Conclusions:

The use of rFVIta for rapid decrease of INR in a patient with FHF prior to an invasive procedure was safe and efficacious. When considering the use of rFVIIa, clinicians should be aware of the risk of thrombosis. In our experience, and in the limited literature on the matter, rFVIIa 40 μg/kg appears to be an appropriate dose for decrease of the INR. Further studies are needed to confirm this finding.
Generic Substitution of Antiepileptic Drugs: A Systematic Review of Prospective and Retrospective Studies
Authors: Yamada Mikiko , Welty Timothy E
Published: October 2011

Objective:

To systematically review the literature on generic antiepileptic drugs (AEDs), evaluate the efficacy and safety of generic AED substitution, and perform pharmacokinetic (PK) analysis using the American Academy of Neurology (AAN) scheme to classify evidence.

Data Sources:

PubMed and Cumulative Index to Nursing and Allied Health Literature searches from January 1, 1980, to October 15, 2010, were performed using the search terms anticonvulsant, antiepileptic drug, carbamazepine, divalproex, ethosuximide, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, phénobarbital, Phenytoin, primidone, topiramate, valproate, valproic acid, and zonisamide; bioavailability, bioequivalence, bioequivalency, bioequivalent, and substitution; and generic.

Study Selection and Data Extraction:

Retrospective and prospective controlled studies of generic substitution of AEDs were included in the review. Non-English-language articles and uncontrolled clinical studies were excluded, Published articles were categorized using the AAN criteria for systematic reviews.

Data Synthesis:

We identified 156 articles. Of these, 20 met our inclusion criteria; 7 were retrospective studies, 6 were prospective studies in patients with epilepsy, and 7 were prospective studies in healthy subjects. All articles were rated Class I to Class III, using AAN criteria. The retrospective studies were categorized as Class III and showed a significant relationship between generic substitution and increased use of health care resources because of seizures or AED toxicity. Prospective studies were categorized as Class I, II, and III. Prospective studies in patients showed no differences between brand and generic drugs in PK parameters of bioequivalence. Three prospective studies in healthy subjects reported significant differences in maximum drug concentrations. Comparison of brand and generic drugs revealed no significant difference in seizure frequency; however, some prospective studies showed significant differences in PK parameters, primarily those not used for bioequivalence determinations.

Conclusions:

There is inconsistency between retrospective and prospective studies of generic AED substitution. The highest levels of evidence indicate that there should not be a problem with generic substitution, although some patients are more prone to problems with the generic products. Some evidence suggests that switches between multiple generic AED products in certain individuals may be problematic.
Change in MicroRNAs Associated with Neuronal Adaptive Responses in the Nucleus Accumbens under Neuropathic Pain
Authors: Imai Satoshi , Saeki Mai , Yanase Makoto , Horiuchi Hiroshi , Abe Minako , Narita Michiko , Kuzumaki Naoko , Suzuki Tsutomu , Narita Minoru
Published: October 2011

Neuropathic pain is the most difficult type of pain to control, and patients lose their motivation for the purposive pursuit with a decrease in their quality of life. Using a functional magnetic resonance imaging analysis, we demonstrated that blood oxygenation level-dependent signal intensity was increased in the ipsilateral nucleus accumbens (N.Acc.) following peripheral nerve injury. microRNAs are small, noncoding RNA molecules that direct the post-transcriptional suppression of gene expression, and play an important role in regulating synaptic plasticity. In this study, we found that sciatic nerve ligation induced a drastic decrease in the expression of miR200b and miR429 in N.Acc. neurons. The expression of DNA methyltransferase 3a (DNMT3a), which is the one of the predicted targets of miR200b/429, was significantly increased in the limbic forebrain including N.Acc. at 7 d after sciatic nerve ligation. Double-immunolabeling with antibodies specific to DNMT3a and NR1 showed that DNMT3a-immunoreactivity in the N.Acc. was located in NR1-labeled neurons, indicating that increased DNMT3a proteins were dominantly expressed in postsynaptic neurons in the N.Acc. area under a neuropathic pain-like state. The results of these analyses provide new insight into an epigenetic modification that is accompanied by a dramatic decrease in miR200b and miR429 along with the dysfunction of “mesolimbic motivation/valuation circuitry” under a neuropathic pain-like state. These phenomena may result in an increase in DNMT3a in neurons of the N.Acc. under neuropathic pain, which leads to the long-term transcription-silencing of several genes.